ABSTRACT IMPACT: This work will standardize necessary image pre-processing for diagnostic and prognostic clinical workflows dependent on quantitative analysis of conventional magnetic resonance imaging. OBJECTIVES/GOALS: Conventional magnetic resonance imaging (MRI) poses challenges for quantitative analysis due to a lack of uniform inter-scanner voxel intensity values. Head and neck cancer (HNC) applications in particular have not been well investigated. This project aims to systematically evaluate voxel intensity standardization (VIS) methods for HNC MRI. METHODS/STUDY POPULATION: We utilize two separate cohorts of HNC patients, where T2-weighted (T2-w) MRI sequences were acquired before beginning radiotherapy for five patients in each cohort. The first cohort corresponds to patients with images taken at various institutions with a variety of non-uniform acquisition scanners and parameters. The second cohort corresponds to patients from a prospective clinical trial with uniformity in both scanner and acquisition parameters. Regions of interest from a variety of healthy tissues assumed to have minimal interpatient variation were manually contoured for each image and used to compare differences between a variety of VIS methods for each cohort. Towards this end, we implement a new metric for cohort intensity distributional overlap to compare region of interest similarity in a given cohort. RESULTS/ANTICIPATED RESULTS: Using a simple and interpretable metric, we have systematically investigated the effects of various commonly implementable VIS methods on T2-w sequences for two independent cohorts of HNC patients based on region of interest intensity similarity. We demonstrate VIS has a substantial effect on T2-w images where non-uniform acquisition parameters and scanners are utilized. Oppositely, it has a modest to minimal impact on T2-w images generated from the same scanner with the same acquisition parameters. Moreover, with a few notable exceptions, there does not seem to be a clear advantage or disadvantage to using one VIS method over another for T2-w images with non-uniform acquisition parameters. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results inform which VIS methods should be favored in HNC MRI and may indicate VIS is not a critical factor to consider in circumstances where similar acquisition parameters can be utilized. Moreover, our results can help guide downstream quantitative imaging tasks that may one day be implemented in clinical workflows.


Mild traumatic brain injury is characterized by a Glasgow coma scale GCS between 13 and 15. It is a frequent pathology in our country because of the increasing number of circulation accidents. Trauma-induced superior oblique palsy usually results from contusion or avulsion of the trochlear nerve. Severe craniocerebral trauma is often associated with the former mechanism, whereas more minor closed-head injuries can decompensate a congenital phoria. We report a patient who developed an isolated trochlear nerve palsy following minor head trauma. Our 53 years-old patient without significant past medical history was victim of a traffic accident. He presented with a complaint of diplopia following head trauma the week prior. He lost consciousness for less than 1 minute. He noticed diplopia immediately upon awakening, but had no other neurologic symptoms. He presented to our emergency department for evaluation. Computed brain tomography (CT) performed did not show any orbital fractures. Ocular exam revealed mild to moderate infraduction deficit and supraduction excess in adduction of the left eye. Left head tilt test was negative. We finally concluded that our patient had a trochlear nerve palsy following the brain trauma. Further Magnetic Resonance Imaging (MRI) revealed an unsuspected tentorial vascular malformation that was compressing the trochlear nerve in its subarachnoid course. In the absence of other features that support decompensation of a congenital trochlear nerve palsy, compressive lesions should be sought in case of fourth cranial nerve palsy following head trauma.


Urachal cancer arises from an embryologic remnant of the urogenital sinus and allantois and accounts for approximately 1% of bladder malignancies. The most encountered histologic subtype is adenocarcinoma. We present a 76-year-old man suspected to have an advanced sigmoid cancer infiltrating nearby organs. A supplemental 18F-FDG PET/CT showed high tracer uptake in a tumorous process coherent with the dome of the bladder wall involving the sigmoid colon. Cystoscopy revealed a normal bladder wall, except for a small edematous area in the anterior bladder. Biopsies from the sigmoid colon and transurethral resection from the bladder confirmed a urothelial carcinoma originating from the urachus. Urachal cancer is a rare entity which accounts for 0.5–2% of bladder cancer  and mostDue to the infiltrating tumorous growth involving the sigmoid colon, small intestines and lymph node metastases no primary tumor resection was performed. The patient was offered palliating oncologic treatment.


ABSTRACT IMPACT: Reversing tumor microenvironment (TME) immunosuppression will help to increase the overall efficacy of treatment of chemo-resistant triple negative breast cancer (TNBC) and mitigate racial disparities in treatment response. OBJECTIVES/GOALS: We have developed an ex-vivo whole tissue culture model to test the feasibility of reversing local immunosuppression in TME by chemokine modulatory (CKM) regimen. Our current objective is to analyze the molecular changes in CKM-treated chemoresistant TNBC from White and Black women and identify factors determining response to CKM. METHODS/STUDY POPULATION: Freshly resected residual TNBC from 20 White and 20 Black women ≥18 yrs old treated with neoadjuvant chemotherapy (NAC) will be procured. Tumor explants will be prepared & cultured in the absence and presence of CKM . Chemokines implicated in cytotoxic T-lymphocyte (CTL)- & MDSC/ Treg attraction will be analyzed using Taqman & ELISA. We will have 80% power to detect a 0.7 standard deviation difference in chemokines between untreated & treated samples within and between cohorts using ANCOVA. Bulk RNA sequencing will be performed on both untreated & treated samples from CKM responding (highest aggregate increase in CTL- and highest decrease in Treg/MDSC-favoring chemokines in the top quartile) and non-responding (bottom quartile) tissues. RESULTS/ANTICIPATED RESULTS: Our preliminary data show that Black patients (pts) with breast cancer (BC) have an immunosuppressive TME associated with poor outcomes. This is similar to other existing literature showing that Black pts with BC have less favorable and more unfavorable chemokines in the TME. We anticipate the chemokine changes with CKM treatment will be larger in the Black cohort given their ability to elicit a robust inflammatory response. Therefore, we expect that CKM treatment will result in favorable TME in both groups and improve outcomes in TNBC, which has the worst prognosis of all subtypes, eliminating a key area of disparity in BC. The proposed transcriptome analysis will help identify key gene networks involved in response to CKM treatment and guide modulating the targets for non-responsiveness to improve efficacy of CKM. DISCUSSION/SIGNIFICANCE OF FINDINGS: Pts with residual disease (RD) after NAC have a 3-yr overall survival 68% vs. 94% for pts with complete response. Blacks have a higher incidence of TNBC with more likelihood of RD & mortality. We anticipate that the existing TME differences can be abrogated by our current CKM regimen or via developing an alternative CKM regimen optimized for Black pts.


Older adults living in subsidized housing are often at high risk for having multiple chronic conditions and nursing home placement. Previous studies in this population have not examined the relationship between social isolation and healthcare utilization. We examine this using Lubben Social Network Scale-6 and self-reported healthcare utilization. Utilizing data from a multi-state non-profit subsidized housing provider, we performed descriptive and multivariate analyses on a sample of older adults . Overall, 95 % reported having a checkup within the last 12 months and an average of less than one emergency room visits (mean= 0.58) or hospitalizations (mean= 0.34). In adjusted models, Socially isolated older adults had lower levels of routine checkup  and higher levels of hospitalizations  compared to older adults who were not socially isolated. Efforts to address healthcare utilization should identify social isolation and explore strategies to promote social connectedness to improve health.


Afferent limb syndrome is obstruction of a biliary-enteric limb following pancreaticoduodenectomy. In the past, treatment was limited to surgery or insertion of a percutaneous transhepatic biliary drainage tube. A more recent approach to treatment is Endoscopic Ultrasound (EUS)-guided gastrojejunostomy using a lumen apposing metal stent (LAMS). It was first described in two single case reports in 2015 and has been growing in its application. We present a case series of 2 patients where afferent limb syndrome was successfully managed with EUS guided gastrojejunostomy using LAMS.1-To demonstrate a novel technique for diagnosis and management of afferent limb syndrome.Case # 1- 79 year old female post Whipple’s surgery for ampullary carcinoma, presented two years after surgery with significant nausea and vomiting. CT scan showed obstruction of the afferent loop suspicious for local tumor recurrence. Patient underwent EUS-guided gastrojejunostomy with successful insertion of 20 x 10 mm  stent.Case # 2-. A 51 year old male with pancreatic CA status post Whipple surgery presented with worsening abdominal pain and nausea. CT scan confirmed afferent limb syndrome. He underwent EUS- guided gastrojejunostomy with successful placement of 10 x 10 mm .Case #1: Patient improved dramatically within days and resumed oral diet. Fourteen days later, an upper endoscopy was performed in order to assess the stricture via an anterograde approach. The adult Olympus HQ gastroscope was advanced through the AXIOS stent into the afferent limb to the level of the stenosis where a tight stricture was seen. Multiple biopsies taken and were negative for malignancy. Four weeks later, she continued to tolerate oral diet well with no abdominal pain or discomfort.Case # 2: Patient continued to do well clinically 12 weeks post operation. Follow-up upper endoscopy was performed to determine the etiology of the obstruction but due to a sharp angulation, the gastroscope could not be advanced through the AXIOS stent. As such, we advanced an adult Olympus 1T gastroscope down to the site of the AXIOS stent and then utilized the Spyglass DS system to advanced deep into the afferent limb to the level of the stricture and took multiple biopsies for diagnostic purposes.Interventional endoscopic management of afferent limb syndrome has been evolving in the past few years with EUS guided LAMS gastrojejunostomy becoming a well stablished modality. We have demonstrated this technique with subsequent endoscopic anterograde assessment. In one of these cases, this anterograde assessment was performed using the cholangioscope in conjunction with the gastroscope to overcome unfavorable angulated anatomy which to our knowledge has not been described in the literature previously.None


Most algorithms for steering, obstacle avoidance, and moving object detection rely on accurate self-motion estimation, a problem animals solve in real time as they navigate through diverse environments. One biological solution leverages optic flow, the changing pattern of motion experienced on the eye during self-motion. Here I present ARTFLOW, a biologically inspired neural network that learns patterns in optic flow to encode the observer’s self-motion. The network combines the fuzzy ART unsupervised learning algorithm with a hierarchical architecture based on the primate visual system. This design affords fast, local feature learning across parallel modules in each network layer. Simulations show that the network is capable of learning stable patterns from optic flow simulating self-motion through environments of varying complexity with only one epoch of training. ARTFLOW trains substantially faster and yields self-motion estimates that are far more accurate than a comparable network that relies on Hebbian learning. I show how ARTFLOW serves as a generative model to predict the optic flow that corresponds to neural activations distributed across the network. When it comes to navigation through diverse, complex environments, animals demonstrate capabilities that far outpace those of machines. Principles derived from biological systems have the potential to catalyze efficient solutions that enhance autonomy in unmanned aerial vehicles (UAVs) and other mobile robotic systems ,2,3,4. NR) and factor it out from the raw optic flow pattern .Lifelong learning: the learning process need not occur in discrete training and prediction phases—learning may continue during operation.Here I present a fast, biologically inspired neural network that learns optic flow templates that can be used to estimate self-motion through arbitrary environments. The approach builds on the fuzzy adaptive resonance theory (fuzzy ART) family of biologically inspired unsupervised learning algorithms ,32. FuzzBuilding on these strengths, I made contributions in two key areas to make the fuzzy ART neural network suitable for learning optic flow and other sensory patterns.First, neurons are fully connected in typical fuzzy ART neural networks. Analogous to multi-layer perceptrons (MLPs), such dense connections do not scale well to the large numbers of features encountered when processing sensory data. Additionally, spatial relationships among features are not preserved. This is problematic for processing optic flow wherein the configuration of the motion vectors in the global pattern is important. I addressed this challenge in ARTFLOW by introducing parallel fuzzy ART modules that tile space on a discrete grid . Each moSecond, fuzzy ART consists of strictly two network layers, which does not afford learning of hierarchical relationships among features at multiple scales. In ARTFLOW, the outputs of topographically close, spatially offset fuzzy ART modules converge in the next network layer . SimilarI evaluated the ARTFLOW network using video datasets of simulated self-motion through dot-defined environments and visually realistic neighborhood and warehouse scenes rendered using the Unreal video game engine. The dot-defined scenes serve as controlled environments with which to test learning on large numbers of optic flow patterns that arise during specific types of self-motion. I decoded activations from the top “MSTd” layer of ARTFLOW to assess how well the learned optic flow templates support accurate heading estimation. I compared performance to an identically structured hierarchical network that replaces fuzzy ART modules with those that rely on the simpler Hebbian learning law.The neighborhood and warehouse datasets were generated using Microsoft AirSim , a simulModel MT neurons exhibit sensitivity to the speed and direction of optic flow signals over time. I based parameter values on known neurophysiology where possible.I positioned 5000 sMT integrates the optic flow signal over time:The net input of each model MT neuron is the average product of the direction and speed inputs within the RF:In Equation , AMT=0.1Equation  with a tm):n value on the 3D dot cloud (T) dataset.I applied the following sigmoid activation function to compute each MT output signal ))NMTx1) oM. The weights between the input and coding layers of the fuzzy ART network are initialized as a 2 C is initially zero.Here I summarize key stages of the fuzzy ART algorithm ,40 implej; and The activation function ,42:(7)Tji index the coding cell currently checked in the ART search cycle. The following function determines the degree of match between the input sample and weight vector i:The ART search cycle determines whether the weights of a previously committed coding cell will be updated based on the current input or a new coding cell will be committed during training. The search cycle checks how close the current input pattern  is applode mode  to enhanThe vigilance threshold The output of each module is a function of the committed coding cell activations (The activation of the committed coding cells across the 64 (8 × 8) modules are concatenated to form the input vector to the single module in the second fuzzy ART layer (henceforth “MSTd layer”). Because the number of committed cells is determined during training, I trained fuzzy ART layers sequentially: I trained the fuzzy ART layer 1 first, froze its weights, then trained the MSTd layer.I trained two decoders (one linear and one nonlinear) using gradient descent to estimate self-motion parameters from the MSTd layer activations. Both decoders were implemented as backpropagation neural networks that use the Adam optimizer with default parameters to minimize mean-squared error (MSE) loss. I standardized both the features and labels. A single-layer MLP served as the nonlinear decoder, which had 250 hidden units and the rectified-linear (ReLU) activation function. Each decoder network had two output units when estimating heading (azimuth and elevation angles) and five output units when estimating rotation . I used early stopping (patience of 5) to halt training when the validation set loss stopped decreasing.I trained ARTFLOW on the training set of each dataset  for 1 epI trained the decoders on the ARTFLOW MSTd layer activations produced to each sample in the training set after learning completed. The reported accuracy reflects decoder estimates of heading and rotation parameters from MSTd layer activations obtained to the test set samples.C optic flow templates, I implemented Sanger’s network in each module, which adapts Hebb’s Rule for learning the top C PCs [I compared ARTFLOW to an identically structured hierarchical network that implements Hebbian learning rather than fuzzy ART in each module. Because the weights of a single Hebbian neuron converge to the first principal component (PC) of its input and fuzzy ART networks learn op C PCs . To facix from Sanger modules during prediction, I applied a logistic activation function:I trained each Sanger’s network with a learning rate of 0.01. Training ceased when differences between weight matrices on successive epochs dropped below a Frobenius norm of 0.01. To prevent negativity in each neural output https://github.com/owlayton/ARTFLOW (accessed on 1 October 2021).I implemented the model and performed simulations using MATLAB R2021b on an Apple MacBook Pro equipped with the six-core 2.9 Ghz Intel Core i9-8950HK processor and 16 GB of memory. Fuzzy ART layers were implemented such that training and prediction computations across modules ran in parallel on the CPU. The code is available on GitHub: I begin by highlighting key properties of the optic flow templates learned by ARTFLOW. Subsequent sections focus on the accuracy of self-motion estimates derived from the network.The ARTFLOW network learned diverse motion patterns that capture distinct characteristics of the optic flow encountered during simulated self-motion through each visual environment (first rows in Many of the learned templates from the 3D dot cloud (T) scene appear qualitatively similar to those from the neighborhood C and groIt is noteworthy that the number of optic flow templates differs across datasets without changes to the hyperparameters. This occurs because the vigilance hyperparameter  and rotational  self-motion parameters from MSTd layer activations after one epoch of training. I evaluated the accuracy on novel optic flow sequences not encountered during training  using linear and nonlinear (MLP-based) decoders. The performance of the ARTFLOW templates was compared with that of a principal component analysis (PCA)-based representation. This was achieved by simulating an identically structured hierarchical network that implemented Hebbian learning (Sanger’s network) in each module instead of fuzzy ART.Estimating heading in the presence of rotation (3D dot cloud (T+R) dataset) represents a much more challenging problem . Accordi display . The conEstimates of pitch and yaw rotation derived from the networks B demonstFuzzy ART layers in ARTFLOW required substantially less time to train than layers in the Hebbian network C. FigureI performed a sensitivity analysis to better understand the robustness of decoded self-motion estimates A,B to che values B. The coe values C. ARTFLOe values B,C. Howee values E,F. The e values D–F.In addition to encoding self-motion, the learned optic flow templates represent a generative model of optic flow. That is, ARTFLOW is capable of predicting the optic flow pattern that corresponds to a set of template activations. This is achieved by propagating the template activations backward layer-by-layer . This contrasts with deep learning networks that require larger amounts of data and many training epochs ,47,48 anA single hyperparameter, vigilance, controls the degree of distinction among the templates. This allows the network to self-regulate the number of templates that are needed to learn optic flow patterns with the desired granularity. Simulations revealed that the accuracy of heading estimation was robust to a wide range of vigilance values in the 3D cloud (T) and warehouse datasets . SensitiARTFLOW not only encodes self-motion parameters more effectively than a comparable network that uses Hebbian learning A but it Several neural networks have been developed that adaptively learn the self-motion templates using Hebbian or Instar biological learning laws ,50,51. HARTFLOW complements work others have done to develop fuzzy ART into a multi-layer network. ARTree ,53 is a Algorithms inspired by the design of the brain have the potential to bridge the gap between machines and animals when it comes to agile, resilient, adaptive navigation. Toward that end, I have presented ARTFLOW, a fast, unsupervised biologically inspired neural network that learns optic flow patterns that support accurate self-motion estimation in diverse environments. The network demonstrates effective encoding of self-motion parameters with one-shot learning and representations that remain stable over continued training.


OBJECTIVES/GOALS: We conducted a review of CTSA websites to understand the current landscape for CRP institutional professional development and training revealed in the CTSA hub websites. METHODS/STUDY POPULATION: We accessed and reviewed 59 currently funded CTSA hub websites for evidence of CRP training opportunities. Parameters reviewed included: 1) opportunities were specified for CRPs versus K and T trainees; 2) mandated training; 3) leveling; 4) delivery methods/resources; 5) public accessibility; 6) unique features. The website reviews informed a REDCap survey sent to the CTSA Administrators (n = 149) and the Coordinator Taskforce (n = 105) listservs to gain additional knowledge of CRP training available at the institution. A subsequent repeat review of the CTSA hub websites will be conducted to determine evolving trends. RESULTS/ANTICIPATED RESULTS: A total of 40 responded to the survey from 59 CTSA hubs. Survey results are being analyzed. Website review data are being tabulated and the subsequent review of websites will be collected in February. Those findings are pending and will include a comparison of prior findings. 42% of CRP hubs list CRP training within the CTSA hub website. Required onboarding training (beyond CITI certificates) is revealed for some hubs (15%). DISCUSSION/SIGNIFICANCE OF IMPACT: On our initial website review less than half of the CTSA hub websites list specific CRP training on their website. Many were hidden behind firewalls and could not be reviewed for content. The REDCap Survey will provide more granular descriptions of programs. Data from a second website review will be collected for comparison. Based on a preliminary re-review of sites, there is a suggestion of increasing CRP workforce development information. CTSAs are well-positioned to be a central hub for promoting educational excellence of the institutional workforce, for medical centers and in other venues where clinical research is performed.


Emerging evidence shows that understanding characteristic patterns between study partners (SP) and subjects can inform initiatives to diversify representation of sociocultural groups in ADRD research. This study examined same-sex spousal dyads with the goal of identifying bellwethers of opportunities to build diversity in ADRD research. Descriptive analysis of The Aging, Demographics and Memory Study (ADAMS), which enrolled a subset of subjects from the Health and Retirement Study and a SP for each subject. Eight same-sex spousal couples were among 718 SP-subject dyads (1.1%). Gay men were 3 times as likely to be spousal SPs (n=6) than lesbians (n=2), even though women far outnumber men overall. Patterns in caregiving and other characteristics also differed. Same-sex couples are underrepresented in ADRD research. Patterns among those enrolled suggest masculine and feminine norms may drive research engagement. This is discussed in the context of increasing sociocultural diversity in ADRD research across key social groups.


Optimal nurse-patient-family interaction is required to provide effective family-centered care for hospitalized older adults and their families. This qualitative descriptive study explored nurses’ interactions with older adult patients and their family members during acute hospitalization. We used semi-structured interviews to collect data from a convenience sample of nine dyads of older adults (aged 62-85) and family members (7 children and 2 spouses) who accompanied them during an acute hospitalization in medical or surgical units. Interviews were performed via Zoom beginning in December 2020 until August 2021, 1-12 months after the hospitalization. Thematic analysis was used to inductively capture key patterns in data. Both patients and family members revealed three factors contributing to the way nurses interact with patients and families: (1) nurses’ recognition and understanding of patients’ needs for family members’ presence and participation in care; (2) nurses recognition that family members expect dedication of attention, beyond nurses’ focus on patient’s care (3) patient and family members’ recognition of the extreme workload of nursing staff. Participants described a range of informal approaches used by both nurses and families to address each other’s needs. Both patients and families emphasize the benefits and costs of nurses engaging in “exceptional” interactions with patients and families considering structural characteristics such as establishing a personal relationship or accepting family visits beyond the rules. The findings provide direction for further exploration of hospitalization structures and processes needed to support optimal nurses’ interactions with families accompanying older adults and family-centered approach training in acute care context.


Surgical treatment of rotator cuff tears commonly entails reattachment of the ruptured tendon to its bony insertion using suture anchors. Suture anchor design has evolved from solid metal anchors to vented biocomposite anchors with potentially biologic consequences. Few studies have investigated the differences between different modern anchor design and materials, making it difficult to justify their use or cost.To compare the rate of bony ingrowth and implant resorption between a coil-type open-architecture biocomposite suture anchor and a vented screw-type biocomposite suture anchor, used for arthroscopic double-row rotator cuff repair.In this retrospective comparative study, a consecutive series of patients who undergo a double row rotator cuff repair using a coil-type open architecture biocomposite suture anchor in the medial row and a vented screw-type biocomposite suture anchor in the lateral row will be included. A sample size calculation demonstrated that 16 participants are required in each group. Primary outcome measures will be bony ingrowth and reabsorption of the suture anchor as measured on computed tomography (CT). Secondary outcomes will include patient reported outcome measures (The American Shoulder and Elbow Surgeons score and The Western Ontario Rotator Cuff questionnaire), range of motion, postoperative tendon integrity, and cyst formation.Open-architecture suture anchors facilitate the release of marrow constituents.The rate of bony ingrowth for coil- and screw-type anchors will be assessed.The difference in functional outcome between the two anchors will be assessed. Suture anchors constitute the primary source of fixation during arthroscopic rotator cuff repair and have undergone several iterations as part of their development. Implant design and composition have evolved with corresponding advances in bioengineering. The primary goal of any such device is to produce a biomechanically stable construct that does not compromise healing of the tendon-bone interface and secondarily to minimize the short and long-term impact on the native anatomy. To achieve this various anchor design and biomaterials have been developed.First-generation bioabsorbable suture anchors were commonly manufactured from polyglycolyic acid (PGA) leading to rapid absorption and an inflammatory reaction in the surrounding bone. As a result of this, tunnel widening and the collection of peri-implant fluid were reported . To mitiin vivo behaviour of these suture anchors is crucial, but few studies have investigated the differences between suture anchors designs [Material properties aside, suture anchors have additionally advanced from conventional solid screw designs to more ‘vented’ suture anchors. Vented suture anchors have additional holes in the otherwise solid anchor body which presumably allows bone in-growth through the implant and access of marrow elements to the bone-tendon healing interface. These vented suture anchor design have now evolved into coil-type open-architecture platforms, which theoretically allow even further bone ingrowth and marrow access despite a lower material load . Despite designs 4.To compare the rate of bony ingrowth and implant resorption between a coil-type open-architecture biocomposite suture anchor and a vented screw-type biocomposite suture anchor, used for arthroscopic double-row rotator cuff repair. We hypothesise that the coil-type biocomposite open-architecture design will lead to greater bone formation and enhanced anchor resorption.The study has been approved by the Conjoint Health Research Ethics Board (CHREB) at the University of Calgary.Retrospective observational study.This retrospective study will be carried out in a tertiary referral centre for complex shoulder arthroscopy and involves patients that had surgery by the senior author (IKL) between April 2015 and February 2019.A consecutive series of patients will be identified from their billing codes and their charts evaluated for implicit consent to take part in research. General eligibility will initially be confirmed by implicit written consent present in the medical records detailing the patient’s willingness to be contacted for involvement in a future study. For those patients, a member of the research team will contact them in order to gain formal consent for this particular study. An appointment for an in-person consultation will be issued so that the relevant outcome measures can be assessed.Inclusion criteria for the study include:A reparable partial/full-thickness supraspinatus/infraspinatus tear.Surgery undertaken with a compression double-row technique exclusively using 4.75 or 5.5 mm Healicoil Regenesorb coil-type open-architecture suture anchors  composed of PLGA/B-TCP/Calcium suphate for the medial low, and 4.75 mm SwiveLock BioComposite vented suture anchors composed of PLLA/B-TCP  for the lateral row.One year minimum follow-up. Patient will be grouped according to length of follow-up to approximately 1 year follow-up and 2 years follow-up.Exclusion criteria comprise the following:A history of shoulder instability.Any previous ipsilateral shoulder surgery.Single row rotator cuff repair.Partial reconstruction of the rotator cuff.A sample size calculation assuming a type I error rate of 0.05, power of 80%, and standard deviation of 50 demonstrated that 16 participants will be required in each group.Preoperative rotator cuff tears will be diagnosed by ultrasonography or magnetic resonance imaging (MRI). The indication for surgery will be ongoing symptoms despite at least six months of non-operative treatment encompassing physiotherapy and analgesia. All operations will be performed by a single surgeon in the following manner:– Patient will be operated under general anaesthesia with regional nerve block as per anaesthesia.– The patient will be placed in the lateral decubitus position.– A standard posterior viewing portal will be utilised for diagnostic arthroscopy with further portals being made according to the desired angle of approach required to reach the rotator cuff.– Subacromial bursectomy will be carried out to aid visualisation and may involve an acromioplasty if an antero-lateral spur is identified.– The rotator cuff tear will be debrided and repaired back to its footprint using a double row repair technique characterised by a 4.75 or 5.5 mm Healicoil Regenesorb anchor  for the medial row, and a 4.75 mm SwiveLock BioComposite anchor  for the lateral row. In general one or two anchors are used medially and one or two anchors are used laterally.A standardised postoperative rehabilitation protocol will be used. In brief, this entails a sling for six weeks, passive range of motion by six weeks, and active range of motion by eight weeks.Outcome measures will be assessed by a blinded musculoskeletal trained radiologist and will include the following:– Primary – Bony ingrowth and reabsorption of the suture anchor.– Secondary – Functional outcome, postoperative tendon integrity, cyst formation, and range of motion.All radiographic measurements will be taken using a computer tomography (CT) scanner  with 1.0 mm continuous slices through the shoulder. Inter-observer reliability will be determined by Cohen’s kappa coefficient.A sterile suture anchor of each type being studied will be scanned by CT to obtain baseline data that will subsequently be used to determine whether the device has been completely reabsorbed and identify the nature of the material found in the location it previously occupied. A board-certified radiologist independent to the study and blinded to the intervention will use a semi-quantitative scoring system modified from that proposed by Haneveld et al to assess this at 12 months and 2-years postoperatively :– Grade 1 – Clearly visible structure.– Grade 2 – Visible structure.– Grade 3 – Partial visible structure.– Grade 4 – Structure not visible.Bony ingrowth into the anchor will be measured at 12 months and 2-years postoperatively. Oblique sagittal and coronal multiplanar reconstruction images will be reconstructed with short- and long-axis views oriented at the anchors along with axial images. Two orthopaedic surgeons blinded to the intervention will assess bony ingrowth using the ossification scale devised by Kim et al, and record the highest value from all image cuts taken  :– Stage 1 – Little or no ossification.– Stage 2 – Some ossification but discontinuous or with a wide lucent rim.– Stage 3 – Ossification with a thin lucent rim.– Stage 4 – Good ossification and vague tract border.Peri-implant cyst formation will be assessed on CT and defined as a gap where the hypodensity between the anchor and the bone exceed 1 mm in at least one image . UltrasoThe Western Ontario Rotator Cuff questionnaire (WORC) and the American Shoulder and Elbow Society (ASES) scores will be used for functional outcome assessment at 12 months and 2-years following surgery . The infTables 1 and 2).Data will be collected from all adult patients, over the age of 16-years, undergoing double row arthroscopic rotator cuff repair by the principal investigator (IKL) using the technique described in section 2.4. The data fields will be based on existing information recorded for each patient as part of the local policy governing medical record keeping for patients undergoing surgery. Specific details that will be collected concern preoperative function of the shoulder being operated upon, operative data, and outcome data . A Student t test will be used to determine differences between pre- and post-operative clinical outcome scores and range of motion. The Chi-squared test will be used to compare the rates of bony ingrowth, suture anchor reabsorption, cyst formation, and postoperative tendon integrity. The statistical significant level will be set at p < 0.05.IKL receives research support and royalties from, and performs consulting, for Smith & Nephew. The remaining authors (TT and ST) do not declare any conflicts of interests.Failure rates following rotator cuff repair have been reported to be as high as 46% . This ha8Coil-type open-architecture suture anchors represent an exciting development because they are able to effectively liberate the bone marrow constituents integral to tissue healing . Few stu2The University of Calgary’s Research Ethics Committee has granted the principal investigator ethical approval for any retrospective clinical study that is conducted at the study institution. The study strictly complies with the regulations set out in that agreement and so no further approval will be required.Results from the study will be presented at international scientific conferences focussed on arthroscopic surgery and published in peer-reviewed journals. The findings will additionally be disseminated to other surgeons across North America to guide policy.


Objective: High-density electromyography (EMG) is useful for studying changes in myoelectric activity within a muscle during human movement, but it is prone to motion artifacts during locomotion. We compared canonical correlation analysis and principal component analysis methods for signal decomposition and component filtering with a traditional EMG high-pass filtering approach to quantify their relative performance at removing motion artifacts from high-density EMG of the gastrocnemius and tibialis anterior muscles during human walking and running. Results: Canonical correlation analysis filtering provided a greater reduction in signal content at frequency bands associated with motion artifacts than either traditional high-pass filtering or principal component analysis filtering. Canonical correlation analysis filtering also minimized signal reduction at frequency bands expected to consist of true myoelectric signal. Conclusions: Canonical correlation analysis filtering appears to outperform a standard high-pass filter and principal component analysis filter in cleaning high-density EMG collected during fast walking or running. I.Bipolar surface electromyography (EMG) has long been the gold standard for recording electrical activity from muscles during locomotion In contrast, high-density EMG is an emerging technology that uses an array of electrodes to measure both the spatial and temporal properties of a muscle et al. measured high-density EMG from the vastus medialis during stationary cycling and found that the muscle fiber conduction velocity was relatively constant during fatiguing exercise et al. recorded high-density EMG activity at a self-selected walking speed and showed that lateral gastrocnemius activity varied spatially in healthy adults et al. measured hamstring muscle activity with a linear array of electrodes at near-maximal running speeds and found large individual differences in spatial activity patterns Recently, studies have shown the potential of high-density EMG in more dynamic settings. Schmitz As running speed increases, so too does the frequency of motion artifacts that contaminate the EMG signal et al. showed that canonical correlation analysis can improve the signal-to-noise ratio of high-density EMG recordings during seated isometric tasks High-density EMG provides an opportunity to leverage statistical processing techniques that are typically unavailable with bipolar EMG recordings. Principal component analysis is often used to extract only the important information from a large set of variables and express it in reduced dimensions Principal component analysis and canonical correlation analysis have also been effective at removing motion artifacts from high-density electroencephalography (EEG) recordings during walking. Both EEG and EMG recordings are susceptible to motion artifacts from movement at the electrode-skin interface, cable sway, and movement of system components The purpose of this study was to compare the results of different signal processing techniques on high-density EMG data during locomotion. We recorded data from two lower limb muscles in healthy individuals walking and running on a treadmill at a range of speeds. We processed their data using three different methods: (1) Standard high-pass filtering of the data with a 20 Hz cutoff frequency; (2) Monopolar and differential EMG channel cleaning using principal component analysis and component filtering; and (3) Monopolar and differential channel EMG cleaning using canonical correlation analysis and component filtering. Based on its effectiveness at removing motion artifacts from high-density EEG recordings, we hypothesized that canonical correlation analysis filtering would result in the greatest reduction in motion artifacts. To our knowledge, this is the first study to investigate the effectiveness of different data processing methods on high-density EMG recorded during walking and running.II.The average number of channels that were rejected from the high-density EMG recordings of each muscle decreased when using component decomposition filtering methods to clean the channel data prior to high-pass filtering . Both prThe greatest EMG activity in the medial gastrocnemius during stance was in the distal portion of the muscle, regardless of the speed and processing method applied to the data . During Compared to the medial gastrocnemius muscle, the spatial distribution of the tibialis anterior EMG activity during swing was more evenly distributed across the measured surface of the muscle . At slowThe frequency content of each differential channel varied based on the processing method that was applied . There wCompared to raw, unprocessed data, each processing method reduced the average overall low frequency spectral amplitude, which is predominantly associated with pure motion artifacts, during running at 5.0 m/s , 0–20 HzIII.Both principal component analysis and canonical correlation analysis component cleaning methods reduced motion artifact content from dynamic high-density EMG recordings more effectively than traditional high-pass filtering of channel data. Canonical correlation analysis reduced the average spectral amplitude more than the other two methods in frequency ranges typically associated with motion artifacts . Principet al. found a similar pattern in the lateral gastrocnemius during the stance phase of walking Contrasting spatial EMG activity patterns were observed in the two muscles we measured. In the medial gastrocnemius, we found the highest electrical muscle activity amplitude in the distal portion of the muscle during stance phase at all walking and running speeds. Cronin Although the spatial activation plots for each muscle appeared relatively similar after applying contrasting processing methods  and 3, tPrincipal component analysis and canonical correlation analysis are analogous, but contrasting, methods that have each been used for isolating and removing noise sources from multivariate time series channel data The physical structure of a high-density EMG system likely contributes to the amount and type of motion artifacts during dynamic conditions. Most high-density EMG systems are typically designed for use in stationary environments. Each electrode array required an attached small adapter unit that was connected to the main EMG amplifier via a 3-meter ribbon cable. Although we taped and wrapped the adapter units and corresponding cabling to the subjects’ legs in an attempt to minimize movement artifacts induced by equipment and cable motions, cable sway and electrode mass are known contributors to motion artifacts in high-density biopotential recording systems There were limitations with this study. To simplify our analyses, we focused on the primary phases of the gait cycle in which each muscle is active . Because muscle activity amplitude and timing vary with gait speed IV.Our results demonstrated that high-density EMG canonical correlation analysis channel decomposition and component cleaning is likely the preferred method for processing high-density EMG during fast walking or running. It provided the greatest reduction in signal content within frequency bands expected to include motion artifacts while minimizing signal reduction within frequency bands expected to contain true myoelectric signal. Electrical phantoms using ground-truth EMG sources could help determine if this signal reduction correctly targeted pure motion artifacts. Future studies that examine a wider range of muscles and different high-density EMG systems would also help validate our conclusions.V.A.16 healthy volunteers  with no history of major lower limb injuries or neurological conditions completed this study. All subjects provided written informed consent before participating, and all procedures were in accordance with the Declaration of Helsinki and approved by the University of Florida Institutional Review Board.B.Subjects walked at two different speeds (1.2 and 1.6 m/s) and ran at four different speeds  on an instrumented treadmill. We randomized the order of the speeds for each subject and recorded data for twenty strides per leg. For safety purposes, all subjects wore a lightweight upper-body harness that did not impede or alter their running mechanics.et al.We attached high-density EMG arrays  to the medial gastrocnemius and tibialis anterior muscles of each subject's right leg . The eleth order Butterworth filter, zero lag) to extract gait event timings.We sampled the high-density EMG monopolar data at 2048 Hz with a bandpass filter of 10-500 Hz. We excluded trials that were corrupted by equipment malfunctions. We recorded ground reaction forces from an instrumented split-belt treadmill . All subjects ran on only one belt of the treadmill across all speeds. We low- pass filtered the ground reaction force data at 40 Hz  on the average number of rejected channels at each speed and the root mean square (RMS) values at each differential channel location. The latter allowed us to produce spatial statistical significance plots (p < 0.05) to reveal the influence of processing methods on high-density EMG spatial activity. To account for possible Type I error, we adjusted our results using a false discovery rate correction


Cornulin (CRNN) is linked with tumour progression. Therefore, it is of interest to document data on the molecular modeling of cornulin (CRNN) for docking with phytocompounds  from Justicia adhatoda L. Thus, wedocument the optimal binding features of these compounds with the cornulin model for further consideration. Cornulin (CRNN) is linked with tumour progression -7. ThereThe full amino acid (495aa) sequence of CRNN is downloaded from the Uniprot Knowledgebase database in FASTA format with accession number Q9UBG3. The NCBI Simple Local Alignment Search Tool (Psi-BLAST)  was usedProCheck  was usedThe Cavity Plus server  was usedThe structure data for 12 compounds from Justicia adhatoda L was downloaded from PubChem database. All the compounds were downloaded in SDF format and converted to the PDB format using Pymol.Molecular docking and visualization were done using a standard procedure using PyRx, AutoDock 4 and Pymol -13.The SWISS-MODEL homology \cornulin was created  using a We document the optimal binding features of phytocompounds  from Justicia adhatoda L with Cornulin in the context of cancer for further consideration.


Scientific Reportshttps://doi.org/10.1038/s41598-020-69342-y, published online 23 July 2020Correction to: The original version of this Article incorrectly stated that coronaviruses have the largest of all reported RNA genomes. This statement has now been corrected for accuracy. In the Introduction,"Coronaviruses have the largest RNA genomes among all viruses."now reads"Coronaviruses have some of the largest RNA genomes among all viruses."The original Article has been corrected.


Sensory function has been linked to cognitive impairment and dementia, but the link between multiple sensory impairments and early cognitive impairment (ECI) is unclear. Sensory function  was measured in 390 BLSA participants  from 2012 to 2018 over a mean 3.6 years. ECI was defined based on 1 standard deviation below age-and race-specific means in Card Rotations or California Verbal Learning Test immediate recall. Cox proportional hazard models examined the risk of ECI for each sensory impairment and across categories of impairments. Vision impairment (vs. no vision impairment) was associated with a 70% greater risk of ECI . Participants with 1 or ≥2 sensory impairments had triple the risk of ECI  compared to those without impairment. Future studies are needed to examine whether treatment for sensory impairments can modify these risks.


Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice. Catheter ablation has become an important treatment option for many AF patients. Catheter ablation has been hypothesized to reduce the need for continued medical therapy for patients with AF, but there are few empirical data which demonstrate this.Objective: The objective of this study was to estimate the impact of catheter ablation on antiarrhythmic drug (AAD) utilization and total drug expenditures among AF patients.Methods: A retrospective analysis using the Truven Health Analytics MarketScan® Research Database was performed. Patients with AF and a catheter ablation procedure who had continuous enrollment in the database 6 months prior to their first ablation and a minimum of 1-year follow-up post first ablation were compared to AF patients who were treated with AADs and not ablation. Propensity matching was used to account for baseline differences between groups, and multivariable regression models adjusted for patient characteristics and baseline healthcare resource utilization. Sub-analyses were performed for patients age ≥65.Results: AF patients treated with catheter ablation had significantly lower AAD utilization and total prescription drug costs than those treated with AADs only. These results persisted for the subset of patients age ≥65. The effects were strongest in the matched sample, where approximately 30% of ablation patients discontinued use of rhythm medication after receiving catheter ablation. Per-patient total medication expenditures were reduced by $800 to $1,200 per year in the matched sample.Conclusion: Catheter ablation for AF reduced AAD utilization and total prescription drug expenditures in a sustainable fashion up to 3 years post ablation. This reduction was consistent and significant in both the non-Medicare and Medicare populations.


Burn shock is one of the most serious and complex complications suffered by patients following thermal injury. Endothelial dysfunction may play a role in the pathogenesis of burn shock. However, the mechanisms underlying the contribution to pathophysiology are still largely unknown. Previous studies have shown a connection between the rearrangement of cytoskeletal elements leading to increased vascular permeability. The aim of this study was to examine the differential expression of genes involved in cytoskeletal arrangement in endothelial cell monolayers treated with plasma from burn patients.Human umbilical vein endothelial cells (HUVECs) were seeded into transwell plates to form confluent monolayers. Plasma was collected from burn patients 4 hours post-admission. HUVEC cells were exposed to 10% multi-donor pooled healthy human plasma (HHP) or burn patient plasma. Monolayers were subsequently incubated with FIT-C Dextran  for 2 hours. Monolayer permeability was measured with indices calculated by normalizing values to blank wells (transwell inserts) and HHP-treated monolayer FIT-C diffusion. RNA was isolated from these same cells that had increased monolayer permeability and PCR analysis was carried out using an 84 gene array of human cytoskeletal regulators (Qiagen). A Ct value of 35 was used to indicate expression and a fold change of 1.5 to indicate differential expression in the control vs. injured groups.Four burn patient plasma samples were utilized to create injuries. Patients were mostly male (75%) with a mean age of 50±20 years and mean %TBSA burn of 37±34%. Differential gene expression in burn vs. HHP was compared. Ten genes showed significant upregulation . Four genes showed significant downregulation in . Monolayer permeability indices showed statistically significant increases when compared to controls ranging from 3-13.33% (p < .05).The interplay of burn shock and endothelial dysfunction remains a complex process of which much is unknown. However, RNA analyses of burn patient plasma reveals involvement of multiple cytoskeletal regulators. Furthermore, all these samples show a concurrent increase in permeability indices when compared to controls, further strengthening the association between cytoskeletal rearrangement and endotheliopathy. Future research to better understand the specifics of these pathways could help aid in the development of more targeted treatments of endotheliopathy and burn shock. Cytoskeletal rearrangement may be an interesting target for future work to understand this mechanistic interplay.


Fall risk increases as older adults lose the functional resources necessary to maintain balance while completing everyday activities. As functional resources often decline gradually with age, momentary deficits may not be apparent until after a fall occurs. Mobile fall prevention technologies could support older adults in self-monitoring their ability to safely navigate their environments. In this paper we present perspectives on self-monitoring and feedback in a sample of older adults  who had self-assessed their balance via a smartphone for 30 consecutive days. Thematic analysis of semi-structured interviews showed that fall history differentiated a) participants’ awareness of day-to-day variation in functional ability; b) trust in the accuracy of self-monitoring; and c) imaginations of what types of feedback a mobile fall prevention technology should provide. Insight on older adults’ internal self-monitoring processes and guidelines for feedback design are discussed.


ABSTRACT IMPACT: Our improved understanding of the changes in chromatin accessibility that occur in persistent pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG. OBJECTIVES/GOALS: Efforts to understand genetic variability involved in an individual’s susceptibility to persistent pain support a role for upstream regulation by epigenetic mechanisms. Our objective was to examine the transcriptomic and epigenetic basis of persistent pain following nerve injury. METHODS/STUDY POPULATION: We used a multiomic approach to identify novel molecular pathways associated with nerve injury-induced pain hypersensitivity. Adult Sprague Dawley rats were randomized to Chronic Constriction Injury (CCI) to the sciatic nerve or no treatment (naive). The ipsilateral L4-L6 dorsal root ganglia (DRG)s were removed on Day 14 and used for ChIP-seq for H3K4me1, ATAC-seq, and RNA-seq. We assessed for differential chromatin accessibility, transcription factor motifs, and enrichment for biological processes in chromatin accessible regions associated with cis-regulatory regions identified by ATAC-seq and H3K4me1 enrichment. Luciferase assays determined the functional significance of these sequences. RESULTS/ANTICIPATED RESULTS: We identified 58,446 genomic regions where H3K4me1 enrichment overlapped with chromatin accessibility. Differential analysis identified 2145 of these 58,446 regions that had changes in accessibility after CCI. The majority of these regions were located in introns or intergenic regions. Functional annotation of the differentially accessible regions identified disparate molecular functions enriched following nerve injury which suggests that altered chromatin structure plays a role in the development of mechanical hypersensitivity. Motif analysis identified specific transcription factor families whose binding sequences were enriched in regions of increased or decreased accessibility. Luciferase assays showed significant enhancement or repression of gene transcription. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our data provides a comprehensive map of chromatin accessibility changes in the DRG after CCI and emphasizes the importance of chromatin structure in the development and maintenance of chronic pain.


Some theories suggest that uneven distribution of collagen fibers in the mitral annulus leaves the posterior mitral annulus without a well-formed fibrous structure, which may predispose it to recurrent mechanical injury that leads to PVL. The reported incidence of PVL is 2.2%.2 Risk factors associated with PVL include the presence of mitral annular calcification, infective endocarditis, active steroid use, and continuous surgical suturing, which poses a greater risk than an interrupted surgical approach.3 Risk of PVL varies by prosthesis type, with mechanical prostheses carrying a higher risk of PVL than bioprosthetic valves.Despite improvements and advancements in surgical technique, paravalvular leaks (PVL) continue to present a challenge when caring for patients with prosthetic valve disease.Figure 1 illustrate a significant posterior PVL with dehiscence of the prosthetic valve from the mitral annulus. The patient underwent closure of the paravalvular leak with two 18-mm Amplatzer ventricular septal defect occluders (Abbott) with excellent results and trace residual mitral regurgitation post closure .Below are images of a 70-year-old male with severe mitral stenosis and pulmonary hypertension who had previously undergone mitral valve commissurotomy and subsequent mitral valve replacement with a bioprosthetic mitral valve. He presented to the hospital with pulmonary edema. Initial transthoracic echocardiogram showed depressed biventricular function with a dehiscence of the bioprosthetic mitral valve and a large eccentric posterior PVL, severe tricuspid regurgitation, and severe pulmonary hypertension. Transesophageal images in


An audit to assess the impact of an Integrated Psychological Medicine Service (IPMS) on healthcare utilization pre & post intervention. We hypothesized that an IPMS approach would reduce healthcare utilization.The IPMS focusses on integrating biopsychosocial assessments into physical healthcare pathways. It has developed in stages as opportunities presented in different specialities leading to a heterogeneous non-standardised service. The key aim is involvement of mental health practitioners, psychologists & psychiatrists in complex patients with comorbidity or functional presentations in combination with the specialty MDT. This audit is the first attempt to gather data across all involved specialities and complete a randomised deep dive into cases.Referrals into IMPS from July 2019 to June 2020 pulled 129 referrals, of which a 10% randomised sample of 13 patients was selected to analyse. 5 patients had one year of data either side of the duration of the IPMS intervention (excluding 8 patients with incomplete data sets).We analysed; the duration & nature of the IPMS intervention, the number, duration & speciality of inpatient admissions & short stays, outpatient attendances, non-attendances & patient cancellations. Psychosocial information was also gathered. One non-randomised patient was analysed as a comparative case illustration.Randomised patients; patient 78's utilisation remained static, patient 71 post-referral engaged with health psychology & reduced healthcare utilisation. Patient 7 increased healthcare utilisation post-referral secondary to health complications. Patient 54 did not attend & increased healthcare utilisation post-referral. Patient 106 had increased healthcare utilisation post-referral from a new health condition. The randomised sample identified limitations of using healthcare utilisation as an outcome measure when contrasted to the non-randomised case .Correlation only can be inferred from the data due to sample size, limitations & confounding factors e.g. psycho-social life events, acquired illness. Alternative outcome measurements documented (e.g PHQ9/GAD7) were not reliably recorded across pathways.The results evidenced that single cases can demonstrate highly desirable effects of a biopsychosocial approach but they can also skew data sets if results are pooled due to the small sample size & heterogeneous interventions. With some patients an increase in healthcare utilisation was appropriate for an improved clinical outcome. This audit identified that utilising healthcare utilisation as an outcome measure is a crude tool with significant limitations & the need to agree tailored outcome measures based on the type of intervention to assess the impact of IPMS.


Older adults are viewed as being vulnerable to COVID-19. Previous research revealed that individuals would internalize or dissociate with attitudes toward aging when they aged. In this study, data collected before the COVID-19 pandemic were compared with those collected during the pandemic to assess whether the pandemic might make older adults internalize or dissociate with attitudes toward aging to a greater extent.123 Hong Kong participants  were recruited in a two-wave survey (wave 1 in 2018 and wave 2 in 2020) on attitudes toward aging and future self-views. After comparing the correlations between attitudes toward aging and future self-views in the two waves, we found stronger positive correlations between these 2 variables in wave 2 than in wave 1 in the personality and finance domains, but not in the family, independence, or health domains. These findings suggest that internalization of attitudes toward aging might be domain-specific. The pandemic might make older adults more likely to internalize positive personality attitudes toward aging and negative finance attitudes toward aging into their future self-views. Professionals may consider utilizing the internalization process to promote a positive attitude toward aging during the pandemic.


Hepatitis B virus-related hepatocellular carcinoma recurrence after liver transplantation (LT) is notoriously difficult to manage and fatal. As a therapeutic option, adoptive cell therapy with HBV-specific TCR-redirected T cells could be employed to target and control relapses in these patients. However, indispensable immunosuppressive medications post-transplantation can significantly hinder the optimum efficacy of such therapy in the clinic. Here we report a new class of Armored TCR T cells which are able to attack recurrent cancer cells in liver transplanted recipients, while temporarily evading immunosuppressant drugs. We believe this strategy could open up new opportunities for treating pathologies under immunosuppressant treatment. Hepatocellular carcinoma (HCC), is the most common type of adult liver malignancy and a leading cause of cancer-related mortality globally. Different etiological factors are involved in HCC development, among which chronic Hepatitis B virus (HBV) infection accounts for approximately 50% of HCC cases globally . Among aOver the past decade, special attention was given to immune based therapy regimens such as immune check point inhibitor (ICI) and adoptive cell therapy as a promising treatment choice for HCC patients. ICIs are a type of immunotherapy drug which aims to rejuvenate and/or induce anti-tumor T cell responses. Clinical trials using ICIs have shown promising outcome in treating primary HCC . HoweverDespite the encouraging outcome of utilizing T cell immunotherapy in the initial trials, various factors present in the patient sera might adversely affect the optimum efficacy of such treatment. One of the main obstacles for implementing immunotherapy in organ transplanted subjects is the post-transplantation immunosuppression (IS) regimens which might hinder the efficacy of T cell therapy in these patients . In case


Knee osteoarthritis (KOA) is one of the most prominent causes of chronic pain, functional impairment, and disability in older adults. The current standards of care for KOA are aimed toward reducing pain and are largely comprised of analgesic medications, but existing pharmacologic approaches often produce significant adverse effects. Moreover, recent evidence suggests that KOA pain is characterized by alterations in pain-related brain mechanisms. Cranial electrical stimulation (CES), which delivers a low-amplitude alternating electric current to the brain, can facilitate the reversal of maladaptive brain function. Portable CES devices can be used at home with real-time monitoring through a secure videoconferencing platform to facilitate high adherence. Thus, the purpose of this pilot clinical study was to examine the preliminary efficacy of remotely supervised CES on clinical pain severity in older adults with KOA. Thirty participants with KOA were randomly assigned to receive 10 daily sessions of remotely supervised CES with 0.1 mA at a frequency of 0.5 Hz for 60 minutes (n=15) or sham CES (n=15). We measured clinical pain severity using the numeric rating scale . Participants  had a mean age of 59 years. Active CES significantly reduced scores on the NRS . Participants tolerated CES well without any adverse events. Our findings demonstrate the promising clinical efficacy of remotely supervised CES for older adults with KOA. Future studies with larger-scale randomized controlled trials with follow-up assessments are needed to validate and extend our findings.


A best evidence topic has been constructed using a described protocol. The three-part question addressed was: In patients with Infrarenal abdominal aortic aneurysm (AAA), Does endovascular abdominal aortic repair (EVAR), AS compared to open surgical repair (OSR), has lower re-intervention rates? The outcomes assessed were the re-interventional rates in both techniques. The best evidence showed that the OSR has lower statistically significant difference rates in re-intervention rates than the EVAR. •Endovascular abdominal aortic aneurysm repair is inferior to the open surgical repair regarding the re-intervention rates.•Long term outcomes of the open surgical repair are better than the Endovascular repair.•Secondary procedures are more in endovascular repair than the open surgical repair of abdominal aortic aneurysm. This fo1.1While consenting a 50-year-old man with AAA for EVAR repair, one of the junior doctors asked; which modality of AAA repair has lower re-intervention rates; EVAR or Open repair?••[Which modality of treatment has lower re-intervention rates];•[EVAR or OSR]?Three Parts Question:1.21.Embase 1974 to June 2021 using the OVID interface:[AAA OR Abdominal Aortic Aneurysm]AND [Open repair OR open surgical repair OR OSR] AND [EVAR OR Endovascular Repair] AND [re-intervention]2.Medline using the PubMed interface:[AAA OR Abdominal Aortic Aneurysm]AND [Open repair OR open surgical repair OR OSR] AND [EVAR OR Endovascular Repair] AND [re-intervention]•Inclusion criteria: all original articles that review the re-intervention rate among patients with AAA who underwent open surgical repair vs. Endovascular Repair.•Exclusion criteria: case reports, systematic reviews, letters to the editor, conference abstracts.The results were limited to English articles and human studies.1.3A total of 261 papers were found using both search engines. We excluded Two hundred twenty-three essays because they were irrelevant based on the titles and or the abstracts. Thirty-eight full-text articles were screened and assessed for eligibility. From these, we identified six papers to provide the best evidence to answer the question.23Treatment of AAA has changed remarkably in the last decade. EVAR is now increasingly used to treat AAA, especially in high-risk and elderly patients . This isThe re-intervention rates are also called secondary procedures and are defined as any endovascular or surgical procedure done after the first intervention. This procedure may be directly or indirectly related to the First aneurysm repair .In this article, we have reviewed the best studies that compared the two AAA repair modalities to evaluate which techniques have lower re-intervention rates.Only one study in our review showed no statistically significant difference between EVAR and OSR in re-intervention rates; this study was conducted by Majid et al. . This stIn contrast, there are another five trials; three of them were Randomized controlled trials which were conducted by Lederle FA et al. , Van SchAccording to the above articles, the best evidence shows a statistically significant lower re-intervention rate among patients with open surgical repair of abdominal aortic aneurysm in comparison to endovascular repair.Not requiredNoneAA: Conducted the literature search and wrote the paper. RI: Assisted in the literature search and Writing of paper. LY: Editing of writing. WSC: Assisted in writing of paper. MI: Assisted in the literature search and writing of paper.


Spinal epidural lipomatosis (SEL) is a rare pathologic growth of histologically normal nonencapsulated adipose tissue in the epidural space. It can cause myelopathy or radiculopathy. Etiologies include chronic exposure to endogenous or exogenous steroids and obesity. Idiopathic forms are much infrequent. We present a case of lumbar SEL compressing the thecal sac in a 50-year-old female patient. A 50-year-old female patient presented to our radiology department complaining of lumbar and right lower extremity pain and weakness. Magnetic resonance imaging (MRI) of the lumbo-sacral spine demonstrated severe circumferential compression of the dural sac (from L5 to S1) caused by significant epidural fat hypertrophy Fig. , a findiSEL is a rare condition characterized by nonencapsulated adipose tissue accumulation in the thoracic or lumbar spinal canal’s epidural space which can cause spinal cord or nerve root compression , 2. It c


Scientific Reports 10.1038/s41598-021-98503-w, published online 23 September 2021Correction to: The Funding section in the original version of this Article was incomplete:“Open Access funding enabled and organized by Projekt DEAL.”now reads:“Open Access funding enabled and organized by Projekt DEAL. The synchrotron xrd research leading to this result has been supported by the project CALIPSO plus under Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020."The original Article has been corrected.


Taenia solium eggs and represents the parasitic disease with the greatest tropism for the human central nervous system,,,A 53-year-old man presented to the emergency department with headache and seizures. Axial fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) revealed a nodular focus in the right temporal lobe with a halo of T2 hyperintensity . Compute


Epidemiological evidence indicates that 3-4% of community-dwelling adults over age 65 years old have functionally limiting deficits in both vision and cognition. The comorbidity prevalence is higher in older age strata and in long-term care. Seniors with co-occurrence of vision impairment and dementia have six times higher odds of disability and higher average annual Medicare fee for service costs  or neither condition . This talk will review evidence that people with early dementia and vision problems can experience improved function through appropriately tailored vision rehabilitation interventions. The talk will provide recommendations for unbiased cognitive assessment in visually impaired people. The session will outline research opportunities regarding the question of whether preventing or treating vision impairment may improve cognitive trajectories and neuropsychiatric symptoms in people with dementia.


Agility in educational delivery has been catalyzed in response to national restrictions mandated by the recent COVID-19 pandemic. Increased use of assistive technologies further aligns with the General Medical Council's aims that medical educators provide an 'accessible training experience'. The study examined medical students' receptiveness to different types of interactive teaching. Two undergraduate cohorts received teaching on the Mental State Examination, either socially-distanced delivered by traditional powerpoint or remotely by mind-mapping software on a tablet hand-held digital device. We required an effective program which would retain the popular interactive elements of Psychiatry teaching and promote inclusivity across students' diverse learning styles.Two cohorts of Year 2 students from the Universities of Dundee and St Andrew's Scottish Graduate-Entry Medicine (scotGEM) course took part in an Introduction to Psychiatry seminar which involved a presentation of the Mental State Examination. One was conducted in a face-to-face setting via traditional PowerPoint. The second was conducted via remote-conferencing with mindmaps of key concepts drawn and screen-shared live to students as teaching progressed.This was a qualitative study, with online links to questionnaires for 24 student participants across 5 domains.  Response options included: strongly disagree, disagree, neutral, agree, strongly agree. A section was also included with open-ended questions pooled for thematic analysis.Response rate reached >60% with >80% respondents answering strongly agree across all domains. Thematic results demonstrated positive responses across both teaching sessions, with the interactive elements valued by students. Comments included: “great job was done with the delivery of the session considering it was online rather than in person”; “drawing element was fantastic”; “Good: interactivity of the session drawing and creativity element”.The Mental State Examination (MSE) via live-drawn mind-maps allows salient clinical information to be conceptualised in non-linear diagramatic format. This paediological approach can offer further access points across wide range of learning styles. This pilot study demonstrated such interactive components of Psychiatry teaching continue to be well received and can be effectively delivered remotely. Such sessions also serve to promote inclusivity, linking those who are geographically distant in addition to the visual learner and the neurodiverse. We aim to incorporate these dynamic teaching sessions into our online induction programs and disseminate Intelligent Tutorials to our remote and rural learners throughout Scotland.


High levels of transcription and alternative splicing are recognized hallmarks of gene expression in the testis and largely driven by cells in meiosis. Because of this, the male meiosis stage of the cell cycle is often viewed as having a relatively permissive environment for gene expression. In this review, we highlight recent findings that identify the RNA binding protein RBMXL2 as essential for male meiosis. RBMXL2 functions as a “guardian of the transcriptome” that protects against the use of aberrant (or “cryptic”) splice sites that would disrupt gene expression. This newly discovered protective role during meiosis links with a wider field investigating mechanisms of cryptic splicing control that protect neurons from amyotrophic lateral sclerosis and Alzheimer’s disease. We discuss how the mechanism repressing cryptic splicing patterns during meiosis evolved, and why it may be essential for sperm production and male fertility. Pre-mRNA RNA splicing is a crucial mechanism in eukaryotes and is required to enable expression of protein-coding RNAs (mRNAs) from most mammalian genes. Splicing joins together exons within nascent RNA transcripts, thus creating open reading frames from split genes. Splicing is carried out by a molecular machine called the spliceosome . For accThe testis is considered a relatively permissive site for gene expression patterns. Most human genes produce multiple different mRNAs by using alternative splice sites or by using different combinations of exons. Such alternative splicing permits single genes to produce multiple mRNA isoforms to help amplify the information embedded in the genome. Particularly high levels of alternative splicing have been detected in the testis and in the brain compared to other tissues . Alternavia two sequential divisions. The first meiotic division is preceded by a long prophase that lasts around 2 weeks in mice, referred to as meiotic prophase I. This is divided up into five sequential sub-stages called leptotene, zygotene, pachytene, diplotene and diakinesis – all characterized by distinct chromosomal behaviors. During meiotic prophase I chromosomes condense, and non-sister chromatids form crossovers and undergo genetic recombination. Subsequently, cells separate sister chromatids through a second cell division called meiosis II. This produces haploid spermatids that after meiosis differentiate into spermatozoa  and Meioc  [Meioc genetic knockout spermatocytes have an unusually short meiotic prophase and do not reach pachytene or diplotene – the developmental window in which RBMXL2 protein is expressed . The loss of splicing factors can cause normally intronic regions to be included within incorrectly spliced mRNAs (rather than being removed by splicing). R-loops form as a result of transcription involving local melting of DNA close to the elongating RNA polymerase, and intronic regions remaining within the pre-mRNA being able to base pair with the melted DNA duplex (forming R loops), leading to DNA damage [Genes encoding mRNAs that are incorrectly spliced in the absence of RBMXL2 are enriched in functions associated with meiosis, chromosome segregation and spermatogenesis (Sara Luzzi unpublished). The inappropriate selection of cryptic splice sites in spermatocytes in the absence of RBMXL2 protein might therefore cause spermatocyte cell death by preventing proper expression of key genes needed for meiosis. RBMXL2 regulates splicing patterns of over a hundred genes during meiotic prophase. Important genes that contain cryptic splice sites that are repressed by RBMXL2 protein include rophase) . Exactlyxpressed . Similar meiosis . The effA damage . In prinA damage , it woulRBMXL2 gene originated via retro-transposition of an mRNA encoded by the X-linked gene RBMX approximately 65 million years ago. As a result of this, the RBMXL2 gene does not contain introns [RBMX gene) become transcriptionally silent during pachytene, within a heterochromatic structure called sex body (or XY body)  . This prRBMXL2 may functionally replace RBMX function during meiotic prophase, either as a direct “like for like” replacement or as a more specialized replacement that has evolved to control specific gene expression pathways needed for meiosis [MDM4 exon 6 [RBMXL2 is only expressed during and immediately after meiosis, so how are the genes controlled by RBMXL2 in the testis normally spliced in other tissues that do not express RBMXL2? A possible answer is that the splice events that are controlled by RBMXL2 during meiosis might be controlled instead by RBMX in other cell types within the body. In this scenario  meiosis . However meiosis . RBMX is4 exon 6 .bona fide splice sites. Cryptic splice site inclusion into mRNAs often disrupts protein-coding reading frames by introducing premature termination codons (PTCs). In cells that are not dividing by meiosis, PTC-containing mRNAs are degraded by an RNA stability pathway called Nonsense Mediated Decay (NMD) that prevents translation into truncated proteins that could be harmful to the cell. However, uniquely in the testes PTC-containing transcripts can become stabilized. This stabilization occurs during meiosis, thus increasing the likelihood of mRNAs originating from cryptic splicing being translated into potentially toxic proteins. The reason for this stabilization is because of meiotic-associated changes in the NMD pathway. One of the core protein components of the NMD pathway is a protein called UPF3B that is encoded by a gene on the X chromosome that is turned off during meiosis by MCSI. As a consequence its autosomal paralogue gene UPF3A becomes active when germ cells enter pachytene [UPF3A induces meiotic defects in a mouse model showing UPF3A expression is critical for meiosis [Why is it important to repress cryptic splice sites during meiosis? Conventional splice sites have evolved to enable exons to be precisely joined together and maintain protein-coding open reading frames. Since cryptic splice sites are usually not used they are not under the same selective pressure as achytene . Genetic meiosis . However meiosis . Hence mPtbp2 causes male germ cells to be prematurely sloughed off into the lumen of seminiferous tubules and defects to accumulate in the Sertoli cells cytoskeleton, suggesting impaired interactions between somatic and germ cells without PTBP2 protein [Other RNA binding proteins are also essential for splicing control during meiosis and have been recently reviewed . However protein . This te protein .Rbmxl2 knockout mouse model [How does cryptic splicing repression by RBMXL2 integrate with other recently discovered aspects of splicing control during meiosis? High-throughput RNA sequencing analysis of purified meiotic spermatocytes and spermatids show that 10% of the alternative splicing events during meiosis occur via intron retention ,24,60. Tse model . HoweverCBX5 gene within leukemia cells [A key question for the future is why do spermatocytes die without RBMXL2 protein, and to what extent does this resemble neuronal cell death in cells depleted for TDP43 activity? Is cell death caused by the loss of specific important proteins as a result of cryptic splicing events in protein coding mRNAs or does cell death result from genotoxic damage caused by accumulation of R-loops from incorrectly spliced mRNAs ? What isia cells ,66. Furt


Thrombus formation in the pulmonary vein (PV) stump after lung resection can cause rare cases of cerebral infarction. These infarctions can result in embolism and ischemia in the relatively large intracranial vessels, severely impacting the quality of life (QOL) of these patients. We performed endovascular thrombectomy successfully for this rare complication after lung lobectomy. A 73-year-old woman with paroxysmal atrial fibrillation (AF) suffered from sudden left complete hemiplegia 19 days after undergoing a left upper lung lobectomy (LUL). Magnetic resonance imaging (MRI) showed middle cerebral artery occlusion. Her left hemiplegia improved after the endovascular thrombectomy. Cardiogenic embolism was first suspected, but contrast-enhanced computed tomography (CECT) showed thrombus formation in the PV stump. We continued anticoagulant therapy, and the thrombus resolved completely two months after the stroke. Our patient had a relatively good outcome due to the immediate reperfusion of the affected area. This embolic source may be overlooked because AF frequently occurs after thoracic surgeries. Care should be taken during the postoperative phase to avoid overlooking these emboli. All thoracic surgeons should be informed about mechanical thrombectomy as an effective treatment for postoperative cerebral infarction. Atrial fibrillation (AF) is a common complication that occurs after lung resection and sometimes causes systemic embolism , 2. HoweThe patient was a 73-year-old woman with hypertension and paroxysmal AF (CHADS2 score: 1). She was not prescribed any anticoagulants but was controlled by antiarrhythmic medications and had not reported tachycardia for a few years. She underwent LUL via video-assisted thoracic surgery for lung adenocarcinoma . The postoperative course was uneventful except for paroxysmal AF, which continued for three days. The patient was then transferred to another hospital.The patient was transferred to our hospital for sudden left complete hemiplegia 19 days after the surgery. National Institutes of Health Stroke Scale 17 and electrocardiography showed AF. Magnetic resonance imaging (MRI) taken 160 minutes after the onset showed acute infarction in the right MCA region and the right M1 occlusion  showed thrombus formation in the left superior PV stump six days after the thrombectomy Figure  - A & B.Thrombus formation in the PV stump is a rare embolic source of cerebral infarction , 4 and hSome reports detected spontaneous echo contrast in the left superior PV stump using intraoperative ultrasonography or transesophageal echocardiogram , 13. TheAF is a common complication that occurs during the early period following lung resection and sometimes causes cardiogenic embolism , 2. AF oThere is no consensus whether perioperative anticoagulated therapy is indispensable after lung resection to prevent the thrombus formation in the PV stump -6, 8-9. In previous reports, infarction following lung lobectomy tends to occur in the relatively large intracranial vessels , 4, 15 aOur patient had a comparatively good outcome due to the immediate treatment. It is critical to consider the possibility of endovascular treatment when neurological deteriorations appear in patients following lung resection. Stroke physicians and thoracic surgeons should be aware that lung resection can be a source of emboli formation.


Hair follicles (HFs) are unique, multi-compartment, mini-organs that cycle through phases of active hair growth and pigmentation (anagen), apoptosis-driven regression (catagen) and relative quiescence (telogen). Anagen HFs have high demands for energy and biosynthesis precursors mainly fulfilled by aerobic glycolysis. Histochemistry reports the outer root sheath (ORS) contains high levels of glycogen. To investigate a functional role for glycogen in the HF we quantified glycogen by Periodic-Acid Schiff (PAS) histomorphometry and colorimetric quantitative assay showing ORS of anagen VI HFs contained high levels of glycogen that decreased in catagen. qPCR and immunofluorescence microscopy showed the ORS expressed all enzymes for glycogen synthesis and metabolism. Using human ORS keratinocytes (ORS-KC) and ex vivo human HF organ culture we showed active glycogen metabolism by nutrient starvation and use of a specific glycogen phosphorylase (PYGL) inhibitor. Glycogen in ORS-KC was significantly increased by incubation with lactate demonstrating a functional Cori cycle. Inhibition of PYGL significantly stimulated the ex vivo growth of HFs and delayed onset of catagen. This study defines translationally relevant and therapeutically targetable new features of HF metabolism showing that human scalp HFs operate an internal Cori cycle, synthesize glycogen in the presence of lactate and modulate their growth via PYGL activity. Although HF epithelial cells contain abundant functional mitochondria3 they preferentially engage in aerobic glycolysis metabolizing 90% of glucose to lactate despite the presence of oxygen5.Anagen hair follicles (HFs) have one of highest rates of cell division seen in any mammalian tissue with correlating high levels of protein synthesis due to ongoing formation of the keratinized hair fibre7, cell metabolic needs extend beyond ATP production. Catabolism of glucose to lactate generate a high flux of metabolic precursors for biosynthesis, providing biomass accumulation9. HFs require energy and metabolite expenditure to maintain high proliferation rates, hair fibre production and hair cycle-associated HF remodelling. The importance of aerobic glycolysis to HF function has been demonstrated in mouse by the crucial role played by the enzyme lactate dehydrogenase and metabolism of glucose to lactate in the activation of epithelial HF stem cells (HFSC)10. Moreover, interplay between HF aerobic glycolysis OXPHOS and glutamine metabolism (glutaminolysis) functions as an important reversible switch between ORS lineage progression and their reversion back to HFSC11.Although aerobic glycolysis is considered energetically inefficient compared to mitochondrial oxidative ATP synthesis (OXPHOS)12. In the classical description of the Cori cycle, lactate from peripheral tissues such as the muscle is transported to the liver where it is converted via gluconeogenesis to glucose  and protect tissues from hyperlactatemia17.In a clinical context, excessive pathological production of lactate at the tissue level or impaired metabolism may cause lactic acidosisose Fig. b13–15 wh19 , producing NADPH and biosynthesis precursors21. The ORS (outer root sheath) of HFs is reportedly rich in glycogen24. A role for glycogen in HF physiology has long been proposed both with regards keratinization23 and hair cycle regulation in mice25 and humans24.Glycogen permits osmotically neutral storage of energy and carbon19 Fig. a. Glucos26, generated lactate may be utilized by the ORS and metabolized to glycogen via an internal HF/ORS Cori cycle, explaining the high levels of glycogen reported in the ORS22. We also asked whether ORS glycogen was available for HF metabolism and whether it played a role in HF function.We hypothesize that as HFs engage in aerobic glycolysis5 maintaining in vivo rates of keratinocyte proliferation, differentiation and hair fibre synthesis27 responding physiologically to a wide range of growth regulatory factors and hormones29. We now demonstrate functional glycogen synthesis and catabolism as well as the presence of an operative human HF Cori cycle. Further we show that inhibition of glycogen phosphorylase (PYGL) prolongs anagen maintenance and hair growth. Together these data show that HFs can utilize lactate from aerobic glycolysis to generate glycogen and that metabolism of glycogen plays an important role in human hair cycle regulation.To investigate this we have made use of isolated human HFs, a unique mini-organ model that can be cultured ex vivo where it continues to engage in aerobic glycolysis and glutaminolysis31 was detected in the suprabasal cells of the bulbar ORS  staining for glycogen25. Glycogen also markedly decreased in ex vivo human anagen VI HFs undergoing spontaneous catagen33 . Telogen  the major glucose transporter in human cells39 was strongly expressed in the ORS of anagen HF  downregulated  crucial in the conversion of glucose into glycogen  co-localizes within the same region of the ORS in anagen HFs as glycogen  is involved both in glycogen synthesis and degradation42. In anagen HF strongest PGM1 IF signal was detected in the cuticle  downregulated in catagen HFs . HFs maintained with GPI showed a statistically significant increase in overall hair follicle elongation over controls  and showed trends towards decreased glycogen levels compared to anagen control HFs although the effects of GPI on glycogen were mixed with 2 patients follicles showing strong response to GPI inhibition of glycogen metabolism but follicles from the third patient appearing to be unaffected  and distinct from the established bulge or stem cells region of human HFs5. The activity of lactate dehydrogenase and lactate production has been shown to drive the activation and maintenance of bulge HFSCs in mice, suggesting that metabolism acts as a stimulus in the switch between dormancy and proliferation10. Lactate generated by glycolysis in muscles is transported to the liver and where through gluconeogenesis lactate can be converted to glucose and replenish glycogen15. We showed that under conditions of nutrient starvation ORS-KC rapidly metabolized glycogen catalyzed by glycogen phosphorylase (PYGL). This demonstrated that glycogen can be utilized by the ORS and may be used as an energy store by the HF.The human HF is known to engage in aerobic glycolysis and to metabolize most of its glucose to lactate43 and the ORS contains all of the enzymes for glucose and glycogen synthesis, we asked whether HFs had an internal Cori cycle and could use lactate to generate glycogen. ORS-KC incubated with lactate significantly up-regulated glycogen levels and gluconeogenic enzymes suggesting that ORS-KC engage in gluconeogenesis and can synthesize glucose and glycogen from lactate and therefore operate an internal Cori cycle. This would allow HF to take up locally produced lactate for the synthesis of glycogen. We observed that the increase in glycogen in response to lactate was transient indicative of the glycogen shunt in which glucose is incorporated into glycogen and upon metabolic demand, enters glycolysis via phosphorylase rather than directly entering glycolysis, coupling glycogen synthesis and breakdown to glycolysis46.Since HF metabolize the majority of their glucose to lactate52. In memory CD8+ T cells, G6P is channelled to glycolysis and to PPP to generate NADPH53. We also observed upregulation of G6PD, a key enzyme of PPP upon the treatment with lactate, suggesting similar mechanism occurring in the ORS.The glycogen shunt is frequently associated with tissues and cells that engage in aerobic glycolysis and allows cells to store glucose as glycogen for future use while maintaining homeostasis of glycolytic intermediates and ATP28 with a glycogen phosphorylase inhibitor (GPI). We used GPI to inhibit PYGL activity rather than siRNA knockdown on mRNA as we found in catagen HF that despite significant decrease in mRNA enzyme (protein) expression remained stable; possibly reflecting the long half-life of metabolic enzymes; moreover, the concentration of siRNA required to knockdown PYGL was toxic to the HF (not shown). GPI significantly stimulated HF growth which correlated with hair fibre production and significantly reduced the number of HFs entering catagen.Although the ORS contains high levels of glycogen it is not known whether this serves any function role-possibly as a HF energy store. To investigate this with regards human HF growth we cultured isolated human HF ex vivo54. our data showing that inhibition of by GPI significantly reduced the number of HF entering catagen suggest that PYGL activity is important for catagen. As the only known action of PYGL is glycogen breakdown this data suggest that glycogen metabolism is essential for catagen possible supplying the energy required for apoptosis. However, while measurement of HF glycogen showed an overall trend towards increased glycogen in GPI treated follicles  in the cuticle and the pre-cortex, together with the transient glucose accumulation suggest that they be may be regions of enzyme activity directed towards rapid keratinization and adapted to quick metabolic changes. Finally, the ORS could probably act as a stable glycogen storage site used both for anagen maintenance and remodelling and regression in catagen. This later role is suggested by our data showing that inhibition of PYGL by GPI significantly reduced the number of HF entering catagen suggesting that glycogen breakdown is essential for catagen but also despite significant decrease in mRNA expression in catagen, protein levels for the enzymes did not change significantly.Finally; glycogen has been proposed to play a role in keratinizationIn conclusion, we have shown that the HF ORS is a major site of glycogen synthesis and functional glycogen storage and is capable of gluconeogenesis. That inhibiting glycogen catabolism ex vivo promotes hair growth and delays catagen, prolonging anagen. This constitutes a promising target for future research with regards HF nutrition and nutrient sensing.27. ORS-KC were isolated as previously described56 with a modification-freshly isolated ORS-KC were seeded in collagen I  coated flasks and cultured in Keratinocyte Serum Free Medium . Starvation was performed by incubation in SILAC RPMI 1640 Flex Medium . PYGL inhibitor  and 2-NBDG  were diluted from stock DMSO solution in culture medium. Lactate  was diluted in culture media.HF units from occipital region were obtained from hair transplant patients and whole scalp skin samples from face lift patients following ethical approval granted by East London and The City Research Ethics Committee 1 (REC Alpha 09/H0704/40) and written informed patient consent, adhering to the Declaration of Helsinki Principles. All samples, slides and biological material were tracked and stored according to the ‘Human Tissue Act’ guidelines. Anagen VI HFs were microdissected and cultured as previously describedTotal RNA was extracted from ORS-KC and HFs using the Qiagen RNeasy Microkit  following the manufacturer’s instructions. cDNA was synthesized using SuperScript VILO cDNA Synthesis Kit . qPCR was performed using Rotor-Gene SYBR Green PCR Kit . Relative expression was determined against B2M-Beta-2-microglobulin.Formalin-fixed paraffin-embedded (FFPE) sections were stained using Periodic Acid Schiff (PAS) Kit , according to manufacturer’s protocol. Negative control sections were digested using porcine α-amylase . Sections were imaged using Nanozoomer slide scanner . PAS quantification was performed using ImageJ software, intensity of staining was calculated in the ORS of HFs and normalized to cell number.Antigen retrieval was performed on 5 µm FFPE tissue sections using Citrate buffer, primary antibodies  were incubated overnight at 4 °C followed by appropriate Alexa Fluor secondary antibodies  and DAPI for nuclear staining. Analysis of immunostaining were performed using DM5000B (Leica) and LSM880 (Zeiss) microscopes.Glycogen was quantified using a coupled enzyme colorimetric Glycogen Assay Kit  according to manufacturer’s protocol, normalized to protein concentration [Pierce BCA Protein Assay Kit ].ORS-KCs and HFs homogenized in RIPA buffer containing protease and phosphorylase inhibitors  were separated using NuPAGE minigels  according to the manufacturer’s instructions then transferred to a Trans-Blot Turbo PVDF membrane  and incubated overnight at 4 °C with primary antibodies  and thereafter with appropriate secondary horseradish peroxidase-conjugated antibodies . Membranes were imaged using Clarity ECL chemiluminescence solution  and visualized using ChemiDoc XRS .P value < 0.05.Biological replicates and number of HFs used are indicated in the respective figure legend. Statistical was carried out using either two-tailed paired t-test, one-way ANOVA or two-way ANOVA with multiple comparisons. Data was expressed as mean ± SEM and considered statistically significant at a Supplementary Information 1.Supplementary Information 2.