Conventional fluoroscopic guidance can provide enough information to precisely insert an occipital screw in ordinary cases. However, the occipital screw creates a potential risk of dural venous sinus injury or thrombosis. In some cases, with dural sinus variation, surgeons must especially be cautious to avoid its injury. We present a rare case of proper occipital screw placement using a navigation system for a pathological odontoid fracture with a high risk of dural venous sinus injury because of anatomical variations in the transverse and occipital sinuses. A 60-year-old man who underwent thyroidectomy at the age of 37 years for thyroid carcinoma developed acute neck pain and quadriparesis due to falling out of bed. He urgently underwent closed reduction and temporary immobilization with a halo-vest for a pathological odontoid fracture and atlantoaxial dislocation. Preoperative contrast-enhanced CT showed an absent right transverse sinus and a prominent occipital sinus as variations of the dural venous sinuses. Occipito-C7 fusion surgery was performed without intraoperative active venous bleeding or postoperative brain disorder by using a navigation system for the occipital screw placement to avoid injury to the dural sinus. Postoperative computed tomography showed bi-cortical occipital screw placement avoiding the prominent occipital sinus. The patient’s postoperative course was uneventful. In this case, although rigid occipito-cervical fixation using bi-cortical occipital screws was needed for the pathological odontoid fracture, the variation of the occipital sinus created a high risk of injury during occipital screw placement with conventional fluoroscopic guidance. There is an anatomical variation of the dural venous sinuses between individuals. Prominent occipital sinus injury may notably cause fatal complications such as massive bleeding or occlusion. Thus, we safely inserted the occipital screws using a navigation system that enabled us to avoid occipital venous sinus injury. Occipital screw placement with a navigation system can be a better option to prevent dural venous sinus injury in cases where there is variation in the dural venous sinuses, such as with a prominent occipital venous sinus. Recent advances in navigation systems for spinal fusion surgery have increased the safety of screw insertion. Navigated pedicle screw insertion has greater accuracy compared to non-navigated insertion for all spinal regions ,2. HowevA 60-year-old man underwent thyroidectomy at the age of 37 years for thyroid carcinoma. He was found to have metastases to the odontoid process and multiple lung metastases on positron emission tomography/computed tomography (PET/CT) one month before surgery. Lenvatinib and radiation therapy were planned because he initially had no neck pain. However, he developed acute neck pain and quadriparesis after falling from bed and was urgently referred to our department. The patient, whose preoperative neurologic loss was graded at modified Frankel C1, exhibited neck rotatory deformity and severe muscle weakness  of the upper and lower limbs bilaterally. CT revealed a pathological odontoid fracture and atlantoaxial dislocation. He urgently underwent closed reduction and temporary immobilization with a halo-vest under general anesthesia and was scheduled to undergo occipito-cervical fusion surgery for definite stabilization. Contrast-enhanced CT after closed reduction showed an absent right transverse sinus and a prominent occipital venous sinus  due to variation of the occipital venous sinus that could cause its injury during occipital screw placement Figure . PreoperPostoperative CT showed bi-cortical occipital screw placement avoiding the prominent occipital venous sinus and no intracranial hematoma Figure .His motor weakness improved to the MMT 4-5 level, and he could walk with one crutch six months after surgery.In this case, occipital screw placement using a navigation system during occipito-cervical fusion surgery avoided injury to the occipital venous sinus that could have been fatal. Occipito-cervical fusion surgery is usually performed for high cervical instability . ImplantOn the other hand, it has been recognized that there are some possible risks such as dural injury, CSF leakage, dural venous sinus injury or thrombosis, and sub- or epidural hematoma during occipital screw placement . Nadim eIn this case, the absent right transverse sinus and the prominent occipital venous sinus as an idiopathic anatomic variation were found on preoperative contrast-enhanced CT. Although rigid occipito-cervical fixation using bi-cortical occipital screws was needed for this pathological odontoid fracture, the variation of the occipital venous sinus created a high risk of its injury during occipital screw placement with conventional fluoroscopic guidance. Thus, we safely inserted the occipital screws using a navigation system that enabled us to avoid injury to the occipital venous sinus. The postoperative course was uneventful without any implant failure. In ordinary cases, conventional fluoroscopic guidance can be enough to precisely insert the occipital screw because navigation needs extra time for registration. However, using a navigation system may be a safe option for variations of the occipital venous sinus, possibly preventing injury during occipital screw placement.There is a great anatomical variation of the dural venous sinuses between individuals. Variations of the dural venous sinus, such as a prominent occipital venous sinus, require attention to the location of the occipital screw. Prominent occipital sinus injury may notably cause fatal complications such as massive bleeding or occlusion. Occipital screw placement with a navigation system can be a better option to avoid dural venous sinus injury in those cases.


Prior research on the causality and directionality between disease and functional limitations is ambiguous. The current study used longitudinal monozygotic twin data to test both directions linking disease burden and functional limitations in middle-aged and older adults, controlling for genetic and familial factors. We also examined potential moderation by psychological well-being. The Twins sub-sample from the first two waves of the longitudinal Midlife in the United States (MIDUS) study was used . Only monozygotic twins (N = 713) were included in analyses. In separate multi-level models, we examined disease burden at MIDUS 2 predicted by functional limitations at MIDUS 1 and MIDUS 2 functional limitations predicted by disease burden at MIDUS 1. Disease burden and functional limitations at MIDUS 2 varied substantially within families. There was no within-family association of earlier functional limitations with change in later disease burden , but there was a within-family association such that the twin with higher baseline disease burden had a greater increase in functional limitations than his/her co-twin . Well-being was not a moderator in either model. We found support for a potentially causal association between earlier disease burden and later increases in functional limitations, consistent with the Disablement Process Model. Sensitivity analyses confirm the detected within-family effect. Possible mechanisms linking disease burden and functional limitations are discussed as potential targets for future research.


A 40-year male presented to the emergency department with the complaints of fatigue that had progressively worsened over the period of 3 months. He had recently emigrated from Mexico, where he worked on a farm and eaten raw watercress. Clinical examination revels pallor of oral mucosa. Laboratory findings showed an increased in absolute eosinophil count of 1400 cells per cubic millimeter (reference range 0-400). Ultrasonography of the abdomen reveled intrahepatic biliary ductal dilatation and magnetic resonance cholangiopancreatography revealed a hilar stricture. Endoscopic retrograde cholangiopancreatography was then performed and large flatworm were visualized emerging from major duodenal papilla.


Adverse childhood experiences (ACEs) may predict markers of neurocognitive performance  and brain health/plasticity . This pilot examined the magnitude of effects between: 1) ACES and EF performance, 2) ACEs and BDNF levels, and 3) EF performance and BDNF levels. We hypothesize that higher ACEs will be associated with poorer EF scores and lower BNDF levels and that lower EF scores will be associated with lower BDNF levels. Given the pilot nature of the study, an emphasis is placed on effect size vs. significance. Participants were 36 middle-aged women enrolled in the NICE SPACES trial . ACES were quantified using the 10-item Adverse Childhood Experiences Scale. EF was measured using the fluid cognition composite from the NIH Toolbox – Cognition Battery. BDNF was estimated using proBDNF levels estimated from serum collected via venipuncture. Higher ACEs levels were not directly associated with EF scores ; but did show a meaningful negative beta coefficient with BDNF levels . EF scores and BDNF showed a positive coefficient that did not reach significance . In a modest pilot of middle-age women, higher ACEs were associated with lower BDNF, indicating greater adversity in childhood is linked to lower neurotrophins levels in adulthood. The lower BDNF levels may help explain poorer performance on cognitive tasks. Larger follow-up studies in more powered samples are warranted given the size of detected coefficients.


The aim for this study was to provide information about how community paramedicine home visit programs best “navigate” their role delivering preventative care to frequent 9-1-1 users by describing demographic and clinical characteristics of their patients and comparing them to existing community care populations.z-tests.Our study used secondary data from standardized assessment instruments used in the delivery of home care, community support services, and community paramedicine home visit programs in Ontario. Identical assessment items from each instrument enabled comparisons of demographic, clinical, and social characteristics of community-dwelling older adults using descriptive statistics and Data were analyzed for 29,938 home care clients, 13,782 community support services clients, and 136 community paramedicine patients. Differences were observed in proportions of individuals living alone between community paramedicine patients versus home care clients and community support clients . We found higher proportions of community paramedicine patients with multiple chronic disease  and mental health-related conditions .When using existing community care populations as a reference group, it appears that patients seen in community paramedicine home visit programs are a distinct sub-group of the community-dwelling older adult population with more complex comorbidities, possibly exacerbated by mental illness and social isolation from living alone. Community paramedicine programs may serve as a sentinel support opportunity for patients whose health conditions are not being addressed through timely access to other existing care providers.ISRCTN 58273216.The online version contains supplementary material available at 10.1007/s43678-021-00153-4. Clinician’s capsuleWhat is known about the topic?Community paramedicine programs are designed to improve access to care for vulnerable patient groups but case finding remains a challenge.What did this study ask?We investigated who community paramedicine patients are and how they compare to clients receiving community care using identical assessment items.What did this study find?Community paramedicine patients have higher proportions of multiple chronic disease and mental health-related conditions than others who receive community care.Why does this study matter to clinicians?Community paramedicine programs support older patients with complex comorbidities and mental illness by offering improved access to collaborative care.Community paramedicine programs address barriers to care faced by community-dwelling older adults (≥ 65 years of age) or other vulnerable patient populations who may otherwise resort to calling an ambulance or visiting an emergency department (ED) –4. CommuWhether community paramedicine home visit programs represent a duplication of community-based services requires further exploration , 25, 26.Our study proposed to identify characteristics of existing community paramedicine home visit patients across multiple jurisdictions and compare them to clients from other community-based care providers. We hypothesized that patients in community paramedicine home visit programs represent a distinct subset of community-dwelling older adults with complex needs and a limited social support structure that contributes to their enrolment in these programs.Our study used routinely collected de-identified secondary data about individuals assessed for their eligibility of home care services or as part of the delivery of community support services or community paramedicine programs across Ontario. We used identical variables from each data set to compare the home care and community support services client populations to those enrolled in community paramedicine home visit programs. This study was approved by Hamilton Integrated Research Ethics Board (#1650D).Information about home care clients included all individuals assessed using the interRAI Home Care (HC) assessment , betweenInformation about clients receiving community support services was obtained from individuals who had been assessed using the interRAI Community Health Assessment (CHA) assessment instrument , betweenData about individuals enrolled in community paramedicine home visit programs were obtained from paramedic services that implemented a standardized assessment instrument as part of the Common Assessments for Repeated Paramedic Encounters (CARPE) study ISRCTN 58273216). Several paramedic services participated in development of the CARPE assessment instrument through a process including literature review 8273216. , and an Six paramedic services implemented the CARPE assessment instrument voluntarily as part of a quality improvement process within existing community paramedicine home visit programs. All paramedic services had similar patient enrollment criteria: diagnoses of Congestive Heart Failure (CHF), Chronic Obstructive Pulmonary Disease (COPD), or diabetes, and health system utilization that included at least three 9-1-1 calls, two ED visits, or one hospital admission in the preceding year , 38. ComData were analyzed using descriptive statistics  for each identical item from the respective assessment instruments . For reporting purposes, items were grouped by domain and collapsed into dichotomous variables to identify presence of disease, health deficits, or indicators of impairment (according to the nature of the respective assessment item). Comparative analysis for each assessment item tested proportions of responses using z-test (with ∝  = 0.05) to investigate differences between the community paramedicine patients and the other cohorts of community-dwelling older adults according to identical fields from the respective assessment instruments. Analysis was completed using SAS 9.4  and excluded incomplete or partial assessments.Table Community paramedicine patients demonstrated higher proportions of COPD, coronary artery disease, diabetes, or CHF  and they displayed higher proportions of associated symptoms —all of which were statistically significant differences. A higher proportion of community paramedicine patients would meet the criteria for further assessment of their mental health, 29.4% when compared to 12.4% in community support services clients. More community paramedicine patients indicated that they had experienced a major life stressor or a decline in social activities in the past 90 days (52.2% compared to 22.5% in home care clients and 25.7% in community support services clients).When comparing community paramedicine patients to community support services clients, little evidence of difference was observed in the proportions of individuals who had difficulty communicating or functional deficits for some Activities of Daily Living and Instrumental Activities of Daily Living  . But the home care client group displayed statistically significant differences, with higher proportions of dependence for all functional items when compared to community paramedicine patients.We found that patients in community paramedicine home visit programs likely represent a distinct sub-group of the community-dwelling older adult population because of numerous differences observed between our cohort groups. Our data suggests that the proportion of individuals with mental health needs, complex co-morbidities, and ongoing health conditions or symptoms are often different between community paramedicine programs and home care and community support services agency populations. Higher proportions of health needs in community paramedicine patients suggests they are a complex patient group who could benefit from more integrated care that includes an interface between multiple care providers—reinforcing a characteristic of many community paramedicine home visit programs , 17. By Duplication of services with other existing community-based health care services is a critique of community paramedicine programs  but, to The inferences drawn from our comparisons should be made cautiously because they are based on a small convenience sample of community paramedicine patients assessed using a prototype assessment instrument. Community paramedicine programs remain relatively small in comparison to the number of clients seen through other established programs delivering community-based care. While the sizes of the sample cohorts present a limitation to the inferences, they are reflective of the differences in sizes of the patient populations and were large enough to power statistical analyses. To further strengthen our analysis, we excluded small counts (< 10) of observations from the community paramedicine cohort.Opportunity exists for further collaboration between community-based support services agencies and home care providers, community paramedicine home visit programs, and other parts of the healthcare continuum—particularly primary care providers—to improve coordination of care to medically complex community-dwelling older adults , 10, 39.Anonymized data were obtained for our study meaning that analysis of cross-membership between cohorts was not possible. It is possible that a handful of patients could have been represented in all three groups and questions remain about the likelihood of this. High levels of cross-membership between groups would have lessened the likelihood of observing differences in our analysis. Future research should aim to provide a complete analysis of health system utilization amongst community dwelling older adults.High proportions of mental health-related conditions were identified in community paramedicine patients. Other research has demonstrated that mental health and social isolation can contribute to repeated 9-1-1 use , 15, 40.Our analysis showed that community-dwelling older adults in community paramedicine home visit programs may represent a distinct patient group with a greater proportion of mood symptoms, ongoing health conditions, and complex comorbidities than comparable patient populations that receive home care or community support services. Enrolment into a community paramedicine home visit program may be indicative of a combination of inadequate social support structures or clinical instability and decline of a patient’s condition. Community paramedicine home visit programs may provide a sentinel support opportunity for community-dwelling older patients whose health conditions are not otherwise being addressed through timely access to other existing care providers.Supplementary file1 (DOCX 16 kb)Supplementary file2 (DOCX 24 kb)Below is the link to the electronic supplementary material.


A best evidence topic has been constructed using a described protocol. The three-part question addressed was: In patients undergoing laparoscopic appendicectomy is Hem-o-lok clip safer than Endoloop ligature for closure of appendiceal stump?The search has been devised and 6 studies were deemed to be suitable to answer the question. The outcome assessed was the safety and cost effectiveness of Hem-o-lok clip (Polymer ligation) versus Endoloop ligature for appendiceal stump closure during laparoscopic appendicectomy. We concluded that Hem-o-lok clip is a safe and feasible tool for appendiceal stump closure. It's also a cost-effective way and could be a cheaper option compared to other measures. A BET p2In performing laparoscopic appendicectomy, which technique is the best for appendiceal stump closure? Is it Endoloop ligature or Hem-o-lok clip? Are there any downsides for using either one of them? Therefore, we decided to conduct a systematic review to look for an evidence-based answer to these questions.3In [patients undergoing laparoscopic appendicectomy] is [Hem-o-lok clip] [Polymer clip] safer than [Endoloop ligature] for [closure of appendiceal stump]?4The search was conducted as following:Embase 1974 to 2021 and MEDLINE® 1946 to November 2021 using the OVID interface.[Laparoscopic appendicectomy OR appendicectomy] AND [ Hem-o-lok clip OR Polymer clip OR Polymeric clip] AND [closure of appendiceal stump] AND [Intraoperative complications OR Postoperative complications OR Leak OR abscess].The search was limited to English language and human studies.5250 articles were found. Out of these 6 deemed to be suitable and met the criteria of our search after removing the duplicate and excluding the irrelevant articles. We only included articles which compared these two methods for appendiceal stump closure and excluded studies which compared other methods.1Conference abstracts2Studies not comparing both techniques3Absence of full-text articles4Low evidence papersExclusion criteria:6.8Four randomized clinical trials and two retrospective studies proved that Hem-o-lock is safe and feasible tool for appendiceal stump closure. It's also a cost-effective way and could be a cheaper option compared to other measures.Not applicable.None.SA: devised the idea of the study, conducted literature search and wrote the paper.TS: assisted in literature search and collecting the data.MO: assisted in literature search and writing the paper.RI: assisted in literature search editing and writing the paper.1.Name of the registry: Not applicable2.Unique Identifying number or registration ID: Not applicable3.Hyperlink to your specific registration (must be publicly accessible and will be checked):Sabry Abounozha (SA), Tamer Saafan (TS), Munzir Obaid (MO), Rashid Ibrahim (RI).Not Applicable.None.


We aimed to examine the usefulness of cystoscopic findings to guide mesh tension adjustment during laparoscopic sacrocolpopexy (LSC) to promote better repair of pelvic organ prolapse (POP) and prevent de novo stress urinary incontinence (SUI). In this technique, the bladder wall was observed using a cystoscope when various traction pressures were applied by pulling the mesh arm with forceps before fixation to the promontory during LSC. Adjustment was performed on 20 patients, and postoperative outcomes of POP repair and development of de novo SUI were evaluated. When excessive traction was applied on the mesh arm, a bladder neck opening and a cord-like elevation in the center of the trigone and posterior wall were observed in all cases. The tension was gradually loosened, and precisely when the above-mentioned cystoscopic finding  disappeared, an anatomically appropriate elevation of the vaginal apex was achieved; the mesh arm was fixed to the promontory. At 6 months after LSC, anterior wall recurrences were diagnosed in four patients (beyond the hymen in one) with few symptoms, while no occurrence of de novo SUI. Cystoscopic findings during mesh tension adjustment in LSC could be useful in achieving improved POP repair.The online version contains supplementary material available at 10.1007/s00192-021-04791-1. Laparoscopic sacrocolpopexy (LSC) is considered an excellent option for apical vaginal prolapse owing to its superior correction rates in treating pelvic organ prolapse (POP) . HoweverA greater reduction in point Aa increased the risk of de novo SUI . Since nKato et al. recently reported an unusual cystoscopic finding in a woman with severe mixed urinary incontinence following LSC . A cord-Twenty women with symptomatic stage 3–4 POP according to the Pelvic Organ Prolapse Quantification (POP-Q) system underwent LSC with mesh tension adjustment under cystoscopic guidance at our center from July 2019–April 2020. The POP-Q was used for objective prolapse assessment before and 3 and 6 months after surgery. Prolapse recurrence was defined as retreatment (pessary use or surgery) or POP-Q stage ≥ 2 prolapse. Prolapse Quality of Life Questionnaire (P-QOL)  was usedThe study was conducted as per the principles of the Declaration of Helsinki and approved by the Institutional Review Board . Informed consents were obtained from all patients.All surgical procedures were performed by two senior surgeons according to the procedure by Wattiez et al. . A polytTable Table Cystoscopic findings along with laparoscopic images are shown in Fig. The CR finding and bladder neck opening were observed in all patients when excessive traction was applied on the mesh arm. An anatomically appropriate vaginal apex elevation was achieved precisely when the findings disappeared.Even after decreasing the pneumoperitoneum pressure, no significant change was observed in the cystoscopic finding, although the mesh tension had slightly diminished.POP-Q was measured at 3 and 6 months after surgery. Although four patients 20%) were diagnosed with anterior wall recurrences, retreatment was not required because the degree of anterior prolapse was POP-Q stage 2  with few symptoms and the apex was sufficiently elevated (point C ≥ –5) in all four patients. In the other 16 patients, all compartments were well repaired . Seven patients had no preoperative SUI symptoms and a negative stress test. Postoperative de novo SUI did not occur in those seven patients


Select kynurenine pathway interventions extend lifespan in invertebrate models and are of interest in treating age-associated diseases. Kynurenine pathway activity is responsive to inflammatory signaling, and we are evaluating the potential for these interventions to increase pathogen resistance and curtail age-associated immune decline in Caenorhabditis elegans and mammals. The kynurenine pathway facilitates the catabolism of tryptophan to nicotinamide adenine dinucleotide (NAD). Our lab has found that supplementing the kynurenine metabolite 3-hydroxyanthranilic acid (3HAA) or inhibiting the enzyme 3HAA dioxygenase (HAAO) extends lifespan in C. elegans. 3HAA has demonstrated pro/anti-inflammatory properties in mammals, suggesting a potential role in immune function. C. elegans have a primitive immune system that lacks an adaptive element, but it recapitulates aspects of innate immune signaling and pathogen response. I hypothesize kynurenine pathway interventions that impact C. elegans’ lifespan similarly improve pathogen resistance and immunity. Interventions within the kynurenine pathway are capable of differentially impacting pathogenesis and lifespan of C. elegans challenged with Psuedomonas aeruginosa. C. elegans subjected to select lifespan-extending kynurenine pathway interventions fared better when challenged with P. aeruginosa at older ages. Additionally, fluorescent infection tracking has displayed decreased infection rates in worms with elevated 3HAA. Our data suggests pro-immune activity is facilitated by 3HAA acting downstream of the dbl-1 pathway in addition to directly inhibiting bacterial growth. Our goal is to discover the mechanism(s) through which the kynurenine pathway interacts with immune function in animals and identify potential targets for clinical therapy in aging populations.


Threatening stimuli seem to capture attention more swiftly than neutral stimuli. This attention bias has been observed under different experimental conditions and with different types of stimuli. It remains unclear whether this adaptive behaviour reflects the function of automatic or controlled attention mechanisms. Additionally, the spatiotemporal dynamics of its neural correlates are largely unknown. The present study investigates these issues using an Emotional Flanker Task synchronized with EEG recordings. A group of 32 healthy participants saw response-relevant images  flanked by response-irrelevant distracters . We assessed behavioural and ERP responses drawn from four task conditions  and subjected these responses to repeated-measures ANOVA models. When presented as response-relevant targets, threatening images attracted faster and more accurate responses. They did not affect response accuracy to targets when presented as response-irrelevant flankers. However, response times were significantly slower when threatening images flanked objects than when neutral images were shown as flankers. This result replicated the well-known Emotional Flanker Effect. Behavioural responses to response-relevant threatening targets were accompanied by significant modulations of ERP activity across all time-windows and regions of interest and displayed some meaningful correlations. The Emotional Flanker Effect was accompanied by a modulation over parietal and central-parietal regions within a time-window between 550-690ms. Such a modulation suggests that the attentional disruption to targets caused by response-irrelevant threatening flankers appears to reflect less neural resources available, which are seemingly drawn away by distracting threatening flankers. The observed spatiotemporal dynamics seem to concur with understanding of the important adaptive role attributed to threat-related attention bias. When attention is drawn by co-occurring threatening and non-threatening stimuli, it biases towards the former. This processing bias, which has been previously called the threat or anger superiority effect –3 is conUsing fMRI, Cisler & Koster  showed tFrom a behavioural perspective, a task derived from Biased-Competition Models seems appropriate to investigate the interplay of attentional mechanisms involved in the attentional bias to threats , 24, 25.Such a proposal has been recently supported by a study designed to address this hypothesis . Parra eThe spatiotemporal dynamics of the neurocognitive mechanisms underpinning this adaptive response are still not well understood. For instance Carretié, 2014  could noPublications contributing evidence on covert/overt attention mechanisms, which are the most relevant to the present study, reported the use of a variety of stimuli including IAPS Images –38, ChinWe followed a component-free approach to unveil the neural correlates of this effect. This approach avoids selection biases of time-windows and electrodes from electroencephalographic (EEG) recordings when contrasting the experimental conditions. Such an approach has been recommended for new tasks or tasks that have not been previously subjected to ERP studies . It alloThe influence of other attention orienting functions such as shifting and engagement, which are necessary to monitor conflict and allocate attentional resources , would lWe predict that if the effect induced by Threatening Flankers does reflect interference occurring during the orienting stages of disengaging attention, early ERP modulation should be observed over the posterior attentional network , 55. MorThirty-two healthy undergraduate students participated in the experiment . Their mean age was 20.2 years old (SD = 2.7) with a mean educational level of 13.9 years (SD = 2.3). This paper builds upon data from the research project: “Emotional processing and its modulation in people reinserted from the Colombian armed conflict, belonging to the high council of the presidency of the Republic of Colombia, Antioquia region” approved by the Ethics Committee of the research unit of the University of Antioquia . This study was conducted in accordance with the ethical standards stated in the Declaration of Helsinki . All parThis task is the one reported in Parra et al.   or a “Threatening Scene/Living Object” (key “n” with a red sticker). There was then an inter-trial interval of 2000 ms during which responses were still recorded see .2 = 0.21, β = 0.20] and had no impact on the key interaction reported. That led them to collapse responses across these stimuli and refer to them as “Object”. We followed the same approach. Trials and blocks were fully randomized across participants. We computed accuracy and response time when threatening and neutral stimuli were presented either as Targets or as Flankers.As our key hypotheses concerned effects driven by real-life emotional images , we followed a 2x2 design: at Central Position–Threat/Neutral as Target (TC-2.A/NC-1.A) and at Peripheral Position–Threat/Neutral as Flanker (TP-2.B/NP-1.B). The living/non-living categories of objects were response irrelevant and were only used to add attentional demands and increase competition. This explains why we did not dichotomize the objects but only the emotional dimension . In fact, Parra et al.  reportedThe Flanker task was synchronized with EEG recording. A 64 electrodes NeuroScan Ltd. system with a 10–10 configuration easy-cap was used for acquisition. The signal was recorded with the software Scan 4.5 using a sampling rate of 1000 Hz. Impedance was kept below 10 kΩ. The assessment was conducted within a Faraday chamber with dimmed lights. Participants were seated 60 cm away from a 17” standard PC monitor where stimuli were presented. The total duration of the testing session was approximately 1 hour.The assessment was carried out in a single session. After completing the Emotional Flanker Task, we carried out an emotional screening procedure using a task that asked participants to rate in the two evaluated dimensions  each IAPS image previously seen using a 5-point Likert scale. This procedure was undertaken to ensure that the perceived valence matched the one reported by Lang et al. .runica  and jader  which are a part of the default EEGLAB. The maximum number of rejected independent components was 5%. A maximum of two trials per condition were discarded during further visual artefact rejection after ICA. Then, we applied a low-pass filter at 30 Hz and epoched the data. Blocks were epoched  with a time window between -200 ms pre- and 800 ms after-stimuli presentation. A baseline correction using the -200 to 0 ms window was applied. Only correct trials entered the ERP analysis. The average number of trials useful for analysis was always above 80%  as implemented in EEGLAB. We rejected components informing high frontopolar activity, which are associated with oculomotor artifacts; as well as other non-ocular signals based on neurophysiological criteria. Following recommendations by Luck , we elimThe Emotional Flanker Task has not been previously used in ERP studies. This would make it difficult to rely on specific ERP components to investigate the electrophysiological correlates of the attentional bias to threat found with such a test. As Kappenman and Luck  acknowlestatcond. We focused on the key contrasts which have previously revealed the Flaker Effect . Threatening images received more correct responses than Neutral Images . Emotion position also yielded a significant effect . Target objects (with flanking IAPS images) attracted more correct responses than Target IAPS images (with flanking objects) . The Emotion type x Emotion position interaction was significant . This reflected an emotion-related discrepancy when IAPS images were presented as targets, whereby Threatening images attracted more correct responses than Neutral images . Such a discrepancy was not observed when IAPS images were presented as flankers .The repeated-measures ANOVA model revealed a main effect of Emotion type . Threatening images yielded faster responses than Neutral Images . Emotion position also yielded a significant effect . Target objects (with flanking IAPS images) attracted faster responses than target IAPS images (with flanking objects) . Crucially, the Emotion type x Emotion position interaction was significant . This indicates that Threatening images presented as Targets were identified faster than Neutral images . However, when Threatening images were presented as flankers, they slowed the detection of Target objects more significantly than when Flankers were Neutral images .The repeated-measures ANOVA model revealed a main effect of Emotion type  or Emotion position . The Emotion type did significantly interact with Emotion position . A post hoc analysis shows that threatening images as targets yielded larger positive amplitudes than neutral images as targets . Such a discrepancy was not observed when images were presented as Flankers .The repeated-measures ANOVA model revealed non-significant effects of Emotion type  or Emotion position . The Emotion type x Emotion position interaction was significant . A post hoc analysis shows that threatening images as targets yielded larger negative amplitudes than neutral images as targets  with the inverted pattern observed when images were presented as flankers .The repeated-measures ANOVA model revealed a non-significant main effect of Emotion type  and Emotion position . The Emotion type x Emotion position interaction was significant . A post hoc analysis shows that threatening images as targets yielded larger negative amplitudes than neutral images as targets . Such an effect was not found for images presented as flankers .The repeated-measures ANOVA model revealed significant main effects of Emotion type  or Emotion position . The Emotion type x Emotion position interaction was significant . The post hoc analysis shows that threatening images as targets yielded larger amplitudes than neutral images as targets . The contrast between images presented as flankers was non-significant . In The repeated-measures ANOVA model revealed a non-significant main effect of Emotion type [Finally, a correlation analysis informed that the amplitude of the activity elicited over parietal and central-parietal regions in the 300 – 400ms time window significantly correlated with reaction time data from the Threat-Central condition, whereby larger amplitudes were associated to slower RT  . Interestingly, a pattern compatible with the behavioural dissociation previously reported using the flanker task was only found over parietal and central-parietal regions in a late time window (550 – 690ms). Our results also reveal that electrophysiological activity correlates with behavioural responses seemingly linked to endogenous attention resources deployed to process response relevant stimuli.The aim of the present study was to investigate whether combined behavioural and ERP evidence would shed new light on the spatiotemporal dynamics of the threat-related attentional bias observed with the Emotional Flanker Task. The literature review undertaken to support the rationale of this study confirmed the relevance of further exploring hypotheses linked to Biased-Competition Models of attention combining behavioural responses drawn from tasks akin to the flanker paradigm with the analysis of electrophysiological responses. Our key findings were: i) Threatening images presented as targets were detected faster and more accurately than Neutral images; however, the same images presented as flankers significantly slowed responses to targets; ii) The behavioural discrepancy observed for responses to Threatening Targets relative to Neutral Targets was accompanied by significant ERP discrepancies over extended brain regions involving frontal, central, parietal, and occipital regions, which expanded from 300ms to 700ms; iii) Contrary to our predictions, ERP discrepancies for Threatening Flankers relative to Neutral Flankers were only observed over parietal and central-parietal regions in a late time window. We now discuss each of these findings.The flanker effect reported by Horstmann et al.  relying Additionally, we found faster and more accurate responses during Threatening Target trials , 67–71 aControlled activity seems to be also underpinned by late ERP activity widely spreading from central and central parietal regions (as denoted by activations found during the late time window over these regions) to frontal and parietal-occipital regions. Activity occurring within a similar time window  has been linked to the encoding of emotional and motivational aspects of images in rich sensory contexts –75 and mOn the other hand, in support to a potential automatic nature of the mechanisms sub-serving the interference effect observed during Threatening Flanker trials, we found slower responses to response-relevant targets when they were flanked by response-irrelevant Threatening images. However, our prediction that ERP modulations during early time widows would underpin such an effect was not supported by our data. We predicted that if the effect induced by Threatening Flankers does reflect automatic interference occurring during the orienting stages of disengaging attention, early modulation of relevant ERP activity  would be observed , 37. InsThreat-related stimuli seem to activate two complementary processes supported by the attentional network. Parra et al.  suggesteWe may suggest that the modulation observed within our earlier significant time window over central-parietal regions when Threatening targets were presented, and the modulation observed over the same regions within a late time window when Threatening flakers appeared may be indexing similar mechanisms. The former would be linked to endogenous processes quickly triggered to uptake information presented in the focus of attention, whereas the latter would reflect processes in charge of widely scanning the environment searching for potential threats when they are imminent, and the circumstances allow to do so. From this perspective, the attentional bias to threat could be a process exogenously triggered and endogenously kept .The fact that we have observed such an attentional bias to threat under subliminal stimulus presentation conditions (200 ms) suggests that triggering such an adaptive response does not need long exposures. An alternative account could be that the sources of neural activity triggering the threat-related bias to response-irrelevant stimuli  are too deep in the brain to be recorded via scalp EEG .It is striking that the function of such a sophisticated attentional system can be disrupted if response-irrelevant threat-related subliminal or supraliminal stimuli appear in the visual field outside the focus of attention , 85. TheThere are some limitations to the present study which we would like to acknowledge. First, although we have previously found that response-key mappings would unlikely explain the patterns of results reported with the Emotional Flanker Task , future The results presented in this study lead us to suggest that the attentional mechanisms involved in adaptive responses to threat-related stimuli seem to operate under different spatiotemporal dynamics. The saliency of threatening stimuli will bias attention whether they fall within or outside the focus of attention. The attention system spares resources that can be quickly deployed towards threat-relevant stimuli. Such a monitoring system operates through controlled processes responsible for extracting information from endogenously attended stimuli  and spares resources to explore salient environmental signals through a feed-forward dynamic mechanism with potential survival value. This functional dynamic associated to threat detection grants our attentional system with an important evolutionary function , 88 and S1 File(DOCX)Click here for additional data file.S1 Data(XLSX)Click here for additional data file.


The authors present a study that included patients treated for CABG procedures, in which CAS and VAS were identified by magnetic resonance angiography. Cerebral magnetic resonance imaging was performed to identify new post-operative subclinical cerebral lesions. Associations between CAS/VAS post-operative cerebral lesions were investigated. Forty-six patients were included in the study. Thirteen percent had significant CAS and 11% had significant VAS. Thirty-five percent had new cerebral infarction postoperatively. The authors found a significant association between the presence of cerebral vessel stenosis and acute cerebral infarction. In this letter to the editor, we emphasize that intraoperative management and monitoring during CPB could be crucial, in particular for patients with CAS and VAS who need urgent cardiac surgery. The optimal management of such patients remains controversial. Gold et al.  showed that high mean arterial pressure (MAP) during CPB reduces the overall incidence of combined cardiac and neurological complications. Johnsson et al.  did not show an increased incidence of perioperative neurologic events with a MAP >70 mmHg during CPB in patients with significant bilateral CAS. Maintaining cerebral regional oxygen saturation index (rSO2) in preoperative range reduces the incidence of postoperative cognitive dysfunction and general morbidity. Near-infrared spectroscopy (NIRS) allows assessment of cerebral oxygen delivery and the demands ratio to the frontal cortex. Routine use of cerebral rSO2 monitoring during cardiac surgery may improve patient’s outcome and shorten hospital stay. Cerebral monitoring using NIRS can identify otherwise unrecognized cerebral hypoperfusion during aortic surgery as well. NIRS has been extensively used in patients undergoing cardiac surgery to find an association between the measurements of cerebral oxygenation and postoperative outcome . Several studies have found an association between intraoperative cerebral oxygen desaturation and postoperative cognitive dysfunction, stroke, and prolonged hospital stay . There is no evidence base for the management of patients with asymptomatic CAS and VAS requiring urgent cardiac surgery. Only a large multicenter international randomized study can provide an evidence base for the management of these patients.Carotid artery stenosis (CAS) and vertebral artery stenosis (VAS) are associated with cerebral infarction after cardiopulmonary bypass (CPB). We read with great interest the article “Cerebral Lesions in Patients Undergoing Coronary Artery Bypass Grafting in Relation to Asymptomatic Carotid and Vertebral Artery Stenosis”, by Wiberg et al.


Married and cohabiting couples have important influences on one another’s stress and well-being. Pandemic-related stress may influence the extent to which couples' stress levels are coregulated. This study examined the experience of nonspecific stress and pandemic-related stress and the moderating role of closeness among couples aged 50 and over in which at least one member had hypertension. A total of 30 couples reported their feelings of closeness to one another in a baseline interview and their feelings of nonspecific stress and pandemic-related stress every three hours for 5 days. There was no difference in closeness and nonspecific stress between husbands and wives. Wives reported greater pandemic-related stress than husbands. Actor-partner interdependence models revealed that wives’ nonspecific stress predicted husbands’ nonspecific stress  and that husbands’ nonspecific stress predicted wives’ nonspecific stress in each three hour period  and these associations were not moderated by closeness. Coregulation in pandemic-related stress among husbands and wives was moderated by wives’ feelings of closeness such that when wives’ feelings of closeness were lower, greater husband pandemic-related stress predicted lower pandemic-related stress for wives  whereas when wives’ feelings of closeness were higher, greater husband pandemic-related stress predicted greater pandemic-related stress for wives . These findings indicate that closeness may have detrimental effects especially when considering emotional coregulation in couples regarding the pandemic.


This cohort study analyzes milk samples from lactating mothers to determine if COVID-19 vaccine–related messenger RNA was detectable in human milk after vaccination. The World Health Organization recommends that breastfeeding individuals be vaccinated and does not advise cessation of breastfeeding following vaccine administration.5 The Academy of Breastfeeding Medicine states that there is little plausible risk that vaccine nanoparticles or mRNA would enter breast tissue or be transferred to milk,6 which could theoretically result in priming of infant immune responses that could alter childhood immunity. However, there are no direct data. To address this knowledge gap, we analyzed milk samples to determine if vaccine-related mRNA was detectable in human milk after vaccination.Messenger RNA (mRNA) vaccines against COVID-19 were recently approved under an emergency use authorization.The institutional review board of the University of California, San Francisco, approved the study. Written informed consent was obtained from all study volunteers in the COVID-19 Vaccine in Pregnancy and Lactation (COVIPAL) cohort study from December 2020 to February 2021. Clinical data were collected by questionnaires. Self-collected milk samples were kept on ice or immediately frozen (at home) until arrival in the laboratory. Samples were collected prior to vaccination and at varied time points up to 48 hours after vaccination. Total RNA was isolated from milk components using the RNeasy Mini Kit (Qiagen). We performed real-time quantitative polymerase chain reaction assay targeting the mRNA used in the COVID-19 mRNA-based vaccines. The BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccines were separately inoculated into prevaccination milk samples, which were processed by the same protocols and used as positive controls for this assay  volunteered for this study . Their cVaccine-associated mRNA was not detected in 13 milk samples collected 4 to 48 hours after vaccination from 7 breastfeeding individuals. These results provide important early evidence to strengthen current recommendations that vaccine-related mRNA is not transferred to the infant and that lactating individuals who receive the COVID-19 mRNA-based vaccine should not stop breastfeeding. In addition, any residual mRNA below the limits of detection in our assay would undergo degradation by the infant gastrointestinal system, further reducing infant exposure. Limitations of this study are the small sample size and few participants who received the mRNA-1273 vaccine. In addition, milk storage conditions may affect mRNA stability. Clinical data from larger populations are needed to better estimate the effect of these vaccines on lactation outcomes.


ABSTRACT IMPACT: This work has the potential to identify targetable pathways conveying resistance to PARP inhibitors that may improve ovarian cancer patient outcomes. OBJECTIVES/GOALS: High grade serous ovarian cancer is the deadliest gynecologic malignancy. PARP inhibitors are an FDA approved targeted therapy that is being used more and more frequently in the clinic. It is vital to understand mechanisms driving resistance to this therapy in order to develop treatments to improve patient responses. METHODS/STUDY POPULATION: RNA-sequencing and transcription factor analysis was used to identify pathways of interest. An AP-1 transcriptional reporter assays was used to confirm results of the transcription factor analysis. An unbiased lentiviral shRNA screen was used to identify AP-1 subunits promoting PARP inhibitor resistance. Lentiviral transduction allowed for the knockdown ATF6. Comet assays and two-plasmid systems were used to determine levels of DNA damage and levels of DNA damage repair respectively. RESULTS/ANTICIPATED RESULTS: PARP inhibitor resistant cell lines have increased WNT signaling which promotes to increased DNA damage repair. PARP inhibitor resistant cell lines also have increased AP-1 transcriptional activity, ATF6 expression, and active p38. ATF6 knockdown and p38 inhibition is sufficient to resensitize cells to PARP inhibition. Upon treatment with PARP inhibitors, ATF6 knockdown as well as p38 inhibition lead to increased DNA damage in PARP inhibitor resistant cell lines. RNA-sequencing reveals a signifcant overlap in downregulated genes in cells treated with a β-catenin inhibitor and cells with an ATF6 knockdown. DISCUSSION/SIGNIFICANCE OF FINDINGS: Due to the increasing prevalence of PARP inhibitors in the clinic, it is vital to uncover mechanisms contributing to resistance. This work has the potential to identify targetable pathways conveying resistance to PARP inhibitors that may improve ovarian cancer patient outcomes.


The COVID-19 pandemic has disrupted older adults’ in-person healthcare services. Many individuals rely on remote communication with their healthcare providers for non-urgent health or mental health issues. The present study investigated the effects of technology learning and depressive symptoms on new adoption of telehealth  to communicate with healthcare providers during the COVID-19 pandemic. A sample of 1,500 Medicare beneficiaries aged 65 or older was selected from the National Health and Aging Trend Study. A series of logistic regressions were performed. Results showed that older adults who learned a new online technology during the COVID-19 outbreak were more likely to adopt telehealth. Also, older adults with a higher level of depressive symptoms were more likely to start using telehealth. The findings highlight the importance of technology training to help older adults go online. Telehealth can be an important coping tool for depressive symptoms during the pandemic.


Aortoenteric fistula is a life-threatening emergency and is associated with high morbidity and mortality. Prompt surgical intervention before the aneurysm ruptures lowers the mortality rate to about 50%. Potential imaging mimics for aortoenteric fistula include retroperitoneal fibrosis, mycotic aortic aneurysm, and infectious aortitis. Secondary aortoenteric fistula has relative higher incidence compared to primary and is more common with open aortic repair versus endovascular stent graft repair. Ectopic gas in the aneurysm sac and extravasation of enteric contrast into the aneurysm sac is diagnostic for aortoenteric fistula. However, enteric contrast is not recommended for routine evaluation of aortoenteric because the aforementioned finding is extremely rare. More common imaging findings include bowel loop appearing adherent to aneurysm sac with associated inflammatory stranding and foci or ectopic gas within the aneurysm sac or interposed between the bowel and aneurysm sac. Here we present a case of 52-year-old male who presents with incidental primary aortoenteric fistula. Aortoenteric fistula is defined as an abnormal communication between the aorta or aortoiliac tree with the gastrointestinal tract and presents as catastrophic gastrointestinal bleeding with annual incidence of primary aortoenteric fistula reported at 0.007 per million (with 250 cases reported in literature) Aortoenteric fistula present as minor "herald" gastrointestinal bleeding followed by later catastrophic life-threatening gastrointestinal hemorrhage Here, we present a case of aortoenteric fistula who underwent open resection of abdominal aortic aneurysm with a right axillary to bifemoral bypass graft.A 52-year-old Caucasian male presented to the outside facility emergency department following a syncopal episode and dysthymia. On arrival his vital signs were within normal limits. No leukocytosis. Chest radiograph and unenhanced CT brain were normal. CT abdomen and pelvis with contrast was performed which showed infrarenal abdominal aortic aneurysm measuring 8.9 × 10.3 cm .Fig. 1CTAdditionally, on retrospect, the loop of jejunum appeared adherent to aneurysm sac, with ectopic air within the partially thrombosed aneurysm sac tracking to and in continuity with intraluminal bowel gas. Findings compatible with primary aortoenteric fistula .Fig. 2AdPatient underwent endovascular aortobiiliac stent graft placement on the same day at outside facility . FluorosFive days following the procedure patient reported bright red blood per rectum with stable vitals and hematocrit. CT angiogram of the abdomen and pelvis was performed which showed normal positioning of aortobiiliac stent graft and no evidence of endoleak. The size of the excluded aneurysmal sac was stable from prior exam. There was interval worsening of ectopic air within the excluded aneurysmal sac. Findings were compatible with known aortoenteric fistula .Fig. 4FiAdditionally, prior to transfer at our facility, CT abdomen and pelvis without intravenous contrast was performed which showed enteric contrast into the excluded aneurysmal sac, confirming known aortoenteric fistula .Fig. 5PrPatient was transferred to our facility for further management. Patient underwent resection of abdominal aortic aneurysm with a right axillary to bifemoral bypass utilizing bifurcated ringed Polytetrafluoroethylene, Aortoenteric fistula was first described in 19th century by a British surgeon Sir Astley Cooper CT findings of primary aortoenteric fistula includes presence of ectopic gas within the excluded aneurysmal sac and/or presence of enteric contrast in the aneurysm sac. Lack of fat plane between the vessel and bowel lumen may be early sign for developing aortoenteric fistula. Ancillary findings for secondary aortoenteric fistula includes peri-graft soft tissue inflammation, and adjacent bowel wall thickening Potential imaging mimics of aortoenteric fistula includes retroperitoneal fibrosis, mycotic aortic aneurysm, and infectious aortitis No patient identifiers are disclosed in current report.


The impact of immune system and inflammation on organ homeostasis and tissue stem cell niches in the absence of pathogen invasion has long remained a conundrum in the field of regenerative medicine. The paradoxical role of immune components in promoting tissue injury as well as resolving tissue damage has complicated therapeutic targeting of inflammation as a means to attain tissue homeostasis in degenerative disease contexts. This confound could be resolved by an integrated intricate assessment of cross-talk between inflammatory components and micro- and macro-environmental factors existing in tissues during health and disease. Prudent fate choice decisions of stem cells and their differentiated progeny are key to maintain tissue integrity and function. Stem cells have to exercise this fate choice in consultation with other tissue components. With this respect tissue immune components, danger/damage sensing molecules driving sterile inflammatory signaling cascades and barrier cells having immune-surveillance functions play pivotal roles in supervising stem cell decisions in their niches. Stem cells learn from their previous damage encounters, either endogenous or exogenous, or adapt to persistent micro-environmental changes to orchestrate their decisions. Thus understanding the communication networks between stem cells and immune system components is essential to comprehend stem cell decisions in endogenous tissue niches. Further the systemic interactions between tissue niches integrated through immune networks serve as patrolling systems to establish communication links and orchestrate micro-immune ecologies to better organismal response to injury and promote regeneration. Understanding these communication links is key to devise immune-centric regenerative therapies. Thus the present review is an integrated attempt to provide a unified purview of how inflammation and immune cells provide guidance to stem cells for tissue sculpting during development, organismal aging and tissue crisis based on the current knowledge in the field. Immune response to injury determines the outcome of the healing process and efficient restoration of organ functions. Thus integrating inflammation and immune system targeted strategies to regenerative therapies is an interesting proposition. Knowledge of how immune system components and inflammatory signals interface with stem cells and progenitor cells in tissue niches is key to develop novel immune-centric regeneration therapies. An inverse relationship between efficient regeneration and immune competence exists as we go up the evolutionary ladder. In mammals as development proceeds injury responses proceed from being regenerative to reparative which resonates with the development of an intricate and complex immune system. A shift in scarless wound healing and regeneration in neonates to imperfect repair in adult mammals is mainly attributed to emergence of an intricate adaptive immune system through development. Primitive immune cells emerging from hematopoietic waves before definitive hematopoiesis have important developmental roles in shaping organogenesis, these cells later co-occupy organ specific niches along with stem cells and adapt to tissue specific functions. However the precise relevance of immune system and their roles in tissue regeneration and homeostasis are only being appreciated recently.versus acute inflammation) 2) timing  3) tissue of interface (immune privilege status) 4) complex niche specific micro-environmental factors  and systemic components . The present review evaluates current knowledge on how immune perturbations and innate immune functions impact stem cell fate decisions and how alarm signals from endogenous niche components including stem cells and their differentiated progeny impact immune-responses in tissue microenvironments in health, aging and disease.Contemporary advancement in technology to fate map cells and availability of precise tools to analyze tissue niches has renewed awareness on the role of immune system in tissue regeneration beyond its traditional role in pathogen immunity. Immune-mechanisms orchestrating repair and/or regeneration from tissue stem/progenitor cells depend on the 1) quality of immune resolution . A vicious loop of DAMP signaling and sterile inflammation if unresolved can drive tissue degenerative processes impacting stem cell functions and regeneration. DAMPs include diverse molecules like uric acid, mtDNA, extracellular ATP, HSPs, amyloid β, S100, HMGB1, and ECM proteins .Drosophila implicated developmental roles of TLRs in establishment of dorsal-ventral axis specification, synaptogenesis and axonal guidance apart from roles in anti-microbial defense (Evolutionarily conserved Pattern Recognition Receptor pathways (PRRs) recognizing altered patterns on microbes, viruses or endogenous danger signals lying at the helm of endogenous tissue surveillance mechanisms guide stem cell fate decisions and are key alarmin sensors . Out of  defense . Since t defense . Balance defense . Similar defense . The ces defense . Endosom defense  and TLR3 defense . Since n defense  it wouldSterile inflammatory signaling seems to be evolutionarily conserved in regulating Hematopoietic stem cell (HSC) production during embryonic development. Studies on HSC emergence in zebrafish and mouse indicate that tonic innate immune cell signaling in the absence of microbial challenge can contribute to HSC orchestration and control of cell numbers much before the development of a functional adaptive immune system. Known IFNγ target genes have been shown to be expressed in human fetal HSCs. Intra-arterial Hematopoietic cluster cells (HCC) emerging from the hemogenic endothelium exhibited an innate immune gene signature with enrichment of TLR pathways and IFN target genes indicating existence of sterile immune signaling networks in both mouse and human fetal HSCs . A combiIn addition to differentiated blood cells both mouse and human HSCs express most TLR family members and their downstream adaptor proteins . Stimulavia endogenous repetitive elements which are specifically expressed during endothelial to hematopoietic transitions during HSC emergence in zebrafish models  are integral constituents of Hematopoietic niches and express a wide range of TLR receptors. Minor variations in TLR expression patterns are noted based on species and their tissue of origin . Triggere defect . Thus TLe defect . Aberranh as EGF . The inah as EGF . Howevervia purinergic cell surface receptors. Autocrine eATP is noted from several cells and eATP levels peak during cellular stress. eATP is an evolutionarily conserved DAMP from mammals, fish, insects and plants. In mammals, eATP is known to bind to cell surface P2 receptors expressed on many tissues throughout the body. P2 receptors are categorized into two major classes: ligand-gated ion channels P2X1-7 receptors and metabotropic G protein-coupled P2Y receptors  of fetal liver hematopoiesis. Further functional diversification in tissues to ILC-1, -2 or -3 is guided by signals as diverse as microbiota, dietary lipids and integrated tissue specific inputs during the perinatal period. However their migratory routes during development and during tissue injury in the adult is still elusive. Coincidently ILC2s co-inhabitate stromal tissue niches and were shown to modify epithelial barriers and affect tissue health. These cells could oscillate between different tonic functional states brought in to play by the functional needs of the tissue when challenged by microbial as well as physiological stresses and can thus function as immune tissue alarms  lack antigen-specific receptors but nonetheless exhibit a broad functional spectrum like adaptive T cells and analogous to the T helper subsets are named as ILC1, ILC2 and ILC3. Despite presence of ILCs in SCID mice as well as immune-deficient humans the conventional immune responses to infection are severely compromised underscoring their role in microbial immunity. Data from mice studies indicate that developmentally they originate from a common innate lymphoid precursor (CILP) which do not possess T and B cell differentiation abilities and then finally infiltrate to different tissue e alarms . Based oe alarms . Addressreg cells) resulted in reduction in HSC pool  or the low-grade constitutively activated alternative pathway which begins with the activation of C3. However, all these three pathways merge at C3 which is subsequently converted to C3a, an anaphylatoxin, and C3b, an opsonin. Further activation of C3 components depends on context specific versatile recognition molecules and receptors on cell and pathogen surfaces such as MBL, C1q and Ficolins. Despite low activation of the alternative pathway as a part of immune-surveillance, surface of healthy cells have complement regulators which prevent further nucleation  decreased ability of HSCs for lymphopoiesis, myeloid biased differentiation, decrease in quiescence and increase in HSC pools 2) mesenchymal progenitor cell in the niche are biased towards adipogenesis  and exhihigh HSCs from aged mice into irradiated young niches resulted in skewed myeloid differentiation from these cells. Further P-selectin high aged HSCs exhibited higher cycling  mice are incapable of bone marrow reconstitution post-irradiation exaggerating the importance of autophagy processes in maintenance of HSC integrity  levels concomitant with metabolic/protein stress. These events are driven by breach of organelle quality control checks and loss of proteostasis which exaggerates intrinsic aging of quiescent HSCs . Disruptntegrity . It is s−/− precursor cell into wild type mice impaired HSPC homing and engraftment efficiencies. Interestingly, it has been proposed that NLRP3 regulates HSC migration by facilitating incorporation of CXCR4 into membrane lipid rafts  signature in the absence of a prevailing infection. Interestingly, HSCs are unresponsive to Interferon due to high thresholds of ISGs. Surprisingly, differentiated derivatives of HSC have a narrow spectrum of ISGs but acquire IFN responsiveness indicating an adaptation of bone marrow microenvironment to protect exhaustion of LT-HSCs but at the same time engage progenitor responsivity to viral challenges . Endogenid rafts . Thus, NSome interesting evidence in the literature indicate inflammatory memory imprinted in the HSC genome due to a previous encounter which is passed on to their differentiated progeny. BCG induced a sustained reprogramming of HSCs and epigenetic modifications were passed on to macrophages/myeloid progeny which induced more protective immunity to virulent mycobacterial infection than naïve macrophages  Cell. SiAged Mesenchymal progenitor cells in the bone marrow as well as other tissues exhibit a senescent phenotype marked by loss of clonogenicity and breakdown of DNA repair responses. Exosomes secreted by senescent stromal cells communicate aberrant instructions to stem cells altering their decisions . Exposurin vivo , in adult mice had been shown to induce α cells to transdifferentiate into beta cells to compensate the loss and rescue the need for exogenous insulin for at least 6 months after β cell ablation . A similA classic example of developmental trans-differentiation is emergence of HSCs directly from hemogenic endothelium . Surpris−/− mice fed with western diet atherosclerotic lesions were observed in aortic roots with a concomitant increase in HDAC3. Even in human patients arteriosclerotic lesions in inflammatory areas were associated with HDAC3. HDAC3 inhibition alleviated EndMT by modulating inflammatory response indicating an intimate link between inflammatory triggers and EndMT in context of arteriosclerosis (In fact EndMT serves as the link between inflammatory factors and plaque growth in atherosclerosis. In ApoEclerosis . Inflammin vivo therapeutic applications. Major bottlenecks include epigenetic instability, functional immaturity of the differentiated cells and subsequent immune rejection and engraftment upon transplantation. Further faithful mimicking of the ultrastructural and intricate functional components of endogenous tissues is a complicated task in vitro. Thus tissue niche based targeting approaches to aid endogenous repair and regeneration is an interesting strategy. Designing rational niche targeting strategies requires adequate knowledge of micro- and macro-environmental factors influencing stem cell decisions in their tissue habitats. Dynamic two-way interactions of stem cells with stromal components and resident or systemically recruited immune system players are pivotal in reshaping tissue response patterns to duress. Fetally patterned immune niches in most tissues are subjected to life-long sculpting in a demand driven process. In this premise inability of stem cells and/or immune niches to detect danger signals and eliminate or constructively adapt to crisis are central to aging, stem cell exhaustion and aberrant trans-differentiation events driving progressive degenerative disease. Thus breaking noxious iterative communication networks at stem cell-immune interfaces would be key for constructive regeneration. This would require identification of major molecular players at aberrant stem cell-immune interfaces to unravel novel immune-centric regenerative therapeutic possibilities which could also serve as biomarkers to detect early degeneration. Niche based targeting approaches would require a holistic understanding of tissue and organismal aging and degenerative processes. Since organismal aging is intimately associated with sterile bone marrow centric inflamm-aging, uncoupling these networks at the organismal levels in degenerative disease contexts could also be one possibility to reestablish tissue homeostasis and recovery. In addition, since innate immune system is ubiquitous in most organs finding unique components and interactors in tissue immune niches would be important to establish tissue directed targeting approaches in specific tissue pathologies without compromising overall immune fitness.Recent technical advancements in iPSC generation, PSC derived organoid cultures and gene editing have opened up new avenues in drug screening and disease modelling in a dish. However the potential clinical applications have not caught pace with the technical knowhow due to limitation of usage of these cells for


Dear Editor,NHS England reports that 4.7 million people are awaiting an operation in England, the highest in a decade. Healthcare systems are seeking methods to limit an accumulating impact on services. Clinical pathways can be used to improve patient outcomes when recovery is relatively predictableIn conjunction with national guidanceTableS1. Patients were split into two cohorts; those admitted before  and during  the pandemic (Table 1). Compliance with 14 ERAS pathway factors, spanning 3 days after the operation and shown to be influential on postoperative outcomesTableThe effect of the COVID-19 pandemic on colorectal ERAS pathway adherence and patient outcomes was explored. Complete methodology and demographics can be found in U test analysis revealed an increase in colorectal surgery ERAS pathway compliance during the pandemic (P < 0.001) compared with before . The 30-day post-discharge mortality rate remained at zero in both groups and no patients tested positive for SARS-CoV-2 PCR swabs during admission.Mann–Whitney The colorectal surgery ERAS pathway has passed the ultimate stress test; it is safe, straightforward and improves outcomes. It should form part of the post-pandemic recovery with the aim to clear waiting lists.Disclosure. The authors declare no conflicts of interest.BJS online.znab208_Supplementary_DataClick here for additional data file.


Pseudomonas aeruginosa deploys a triggerfactor to hijack the lysogenic to lytic switch of a polylysogenic Staphylococcus aureus strain causing the selective productionof only one of its prophages. Fractionating extracts of P. aeruginosa identified the phenazine pyocyaninas a highly potent prophage inducer of S. aureus that, in contrast to mitomycin C, displayed prophageselectivity. Mutagenesis and biochemical investigations confirm theexistence of a noncanonical mechanism beyond SOS-response that iscontrolled by the intracellular oxidation level and is prophage-selective.Our results demonstrate that human pathogens can produce metabolitestriggering lysogenic to lytic conversion in a prophage-selective manner.We anticipate our discovery to be the starting point of unveilingmetabolite-mediated microbe–prophage interactions and layingthe foundations for a selective small molecule controlled manipulationof prophage activity. These could be for example applied to controlmicrobial communities by their built-in destruction mechanism in anovel form of phage therapy or for the construction of small molecule-inducibleswitches in synthetic biology.Bacteriophages havemajor impact on their microbial hosts and shapeentire microbial communities. The majority of these phages are latentand reside as prophages integrated in the genomes of their microbialhosts. A variety of intricate regulatory systems determine the switchfrom a lysogenic to lytic life style, but so far strategies are lackingto selectively control prophage induction by small molecules. Herewe show that  This is even more surprising since bacteriophages,viruses infecting bacteria, are the most diverse and abundant biologicalentities on our planet.Microorganisms engagein an enormous diversity of ecological interactionsthat are largely controlled by small molecule metabolites.5 Altered phage compositionin the gut has been linked with human diseases,8 and phages maycontribute to maintenance of intestinal immune functions.9 The vast majority of phages in the human gutare residing integrated as prophages in the genomes of their respectivemicrobial hosts.10 These prophages canbe induced under certain conditions to resume a lytic lifestyle resultingin the production of virus particles (virions) and the destructionof the host cell.11 This typically involvesinactivation of a prophage repressor via the SOS-response.12 Genotoxic agents like mitomycin C trigger thisSOS-response through DNA damage prompting the expression of multiplegenes encoding repair pathways.13 Althoughphages during the lytic cycle destroy their host, a prophage confersvarious fitness benefits to its microbial host.15 These include for example the introduction of toxins and other virulencerelated factors encoded by the prophage,17 protection from superinfection by other phages, and serotype conversionby modulating the structure of lipopolysaccharide O-antigens.19 For bacterial populations, liberated phage particles of spontaneouslysis events of individual cells also may serve as a form of bacterialwarfare against nonlysogenized competitors.14 Thus, prophages are not only a bacterium’s Achilles heelbut also important mutualistic traits and possibly even a key forcontrolling microbial communities.The human body and its microbiota harboran enormous diversityof phages. These phages drive microbial evolution and dynamicallyshape microbial communities.20 and the internalregulation of the lysis-lysogeny decision of prophages via quorumsensing signals of the bacterial host21 or its phages.23The chemistry of microbe–phageinteractions still remainsunderexplored, although recent work has reported defense compoundspreventing lytic infectionsHere we expand the repertoireof small-molecule-mediated microbialinteractions by the discovery of a cross-species prophage inducingmetabolite and prophage-selective trigger factor.Staphylococcus aureus usinga plaque assay. Mitomycin C is used as standard agent for phage induction,24 which causes DNA damage and induces phages byeliciting the bacterial SOS-response.13 Phage particles were quantified as plaque forming units (PFU) onagar plates with the phage-susceptible S. aureus reporterstrain RN4220. Staphylococcus aureus strain ATCC6341 gave a strong prophage induction with mitomycin C and was consequentlyused for a screening of solid phase extracts of culture supernatantsof human commensals and pathogens that are frequently occupying thesame niches  To explore this possibility, we firsttested the inducibility of prophages by the antibiotic mitomycin Cin five human isolates of e niches 1a. Whileagnitude 1b. We thSupporting Information Figure S1). High resolution mass spectrometry resulted in an m/z of 211.08635 indicating a molecularformula of C13H10N2O . Structureelucidation by 1D and 2D NMR spectroscopy ultimately identified pyocyaninas the active compound .The characteristicblue coloration of the active fraction suggested that the inducermay be a phenazine. The active compound was obtained by activity-guidedfractionation by liquid–liquid extraction with subsequent HPLC-purificationto homogeneity .The activity of the isolatedcompound was identical with commercial pyocyanin and led to concentrationdependent prophage induction with up to 1.7 × 10phzM transposon mutant of P. aeruginosa which maintains an intact phenazine gene cluster but is unable toperform the N-methylation step in the biosynthesis of pyocyanin: incontrast to metabolite fractions of wild type P. aeruginosa, those of the ΔphzM mutant did not causephage induction . In order to gain a moredetailed understanding of prophage induction by pyocyanin, we usedsingle-molecule real-time sequencing (PacBio) of the entire genomeof S. aureus ATCC 6341. Analysis of the assembledgenome with Phaster25 identified six prophage-likeregions (PLR I–VI). Two of them (I and VI) were Staphylococcusaureus pathogenicity islands (SaPImbl1 and SaPImbl6), one(V) was tentatively characterized as incomplete prophage, and threeregions  were identified as Siphoviridae (phiMBL2-4) . Production of phage particles was investigated by PCR analysis.We hereby took advantage of the fact that DNA packed in capsids iswell protected from nucleases and can thus be differentiated fromfree genomic DNA of disrupted bacterial cells. The cell-free supernatantsof induced cultures were DNase treated to digest genomic DNA of lysedcells, whereas DNA packed inside phage particles would remain intact. DNasewas then inactivated and the capsids were disrupted by a heat denaturationstep.Mitomycin C causeda maximum of phage induction at 1.5 μM, while at higher concentrationseffective phage production was probably prevented by increasing celltoxicity. Remarkably, the effectiveness of pyocyanin in prophage inductionof Supporting Information Figure S6b).Subsequently, diagnostic fingerprint regions were amplifiedby PCR using sequence-specific primers. All of the six prophage-likeregions could be detected after induction with mitomycin C, whileonly one (phiMBL3) was found with pyocyanin .In order to test which of these were further infectious tophage-sensitive S. aureus phage phiJB (99.5% at 68%coverage). TEM experiments confirmed a phage with Siphoviridae morphology with a tail length of 180 nm and a head diameter of 60nm . Pyocyanin is known to interfere with the electron transportchain in S. aureus and to cause oxidative stress.27 Using a 2′,7′-dichlorofluorescein diacetate (DCF-DA)fluorescent sensor for reactive oxygen species (ROS), we confirmeda strong increase of ROS in S. aureus ATCC 6341 upontreatment with pyocyanin at concentrations used for prophage induction. Wethus investigated if scavengers of reactive oxygen species would protectcells from pyocyanin-mediated prophage induction. Indeed, N-acetylcysteine significantly reduced the production ofthe phage in concentration dependence by more than 2 orders of magnitude,suggesting that the oxidative environment rather than any direct interactionof pyocyanin with a host protein is responsible for prophage induction.To investigate whether any type of ROS or electron transport chaininhibition would cause phage induction at levels and selectivity comparableto pyocyanin, we tested hydrogen peroxide and trans-Δ1-NQNO treatment compared to pyocyanin . More importantly, whilepyocyanin was selective for phage phiMBL3, both hydrogen peroxideand trans-Δ1-NQNO led to productionof multiple phages . Similar to mitomycin C, also hydrogen peroxide is knownto elicit the SOS-response in S. aureus by oxidativeDNA damage29 and quinolone N-oxides may indirectly cause the same effect.30 These results suggest that the mechanism of induction bypyocyanin relies on a high level of ROS production but strictly differsfrom that of other oxidants and electron transport chain inhibitors.This low responsiveness matchedconsiderably lower ROS levels thatwere measured for hydrogen peroxide and R) mutants of S. aureus ATCC 6341over several days of continuous exposure. These pyoR mutantsexhibited MIC values for pyocyanin of 150–200 μM correspondingto up to 4-fold enhanced tolerance compared to the wild type. In comparisonto the wild type, pyoR mutants displayed identical phageinduction with mitomycin C but approximately 2 orders of magnitudelower response to pyocyanin, confirming the different induction mechanismsof both compounds  in the NAD(P)/FAD-dependentoxidoreductase gene as the only shared feature (Supporting Information Table S4). Mutation of the oxidoreductase likely limited redoxcycling of pyocyanin and thereby decreased oxidative stress and henceprophage induction. We suspected that the mechanistic differencesfor the induction of the prophages may be reflected by different typesof prophage repressors.With the aim to gain further insights into the mechanism and itsconnection to prophage induction, we selected three pyocyanin resistant. While phiMBL2 and phiMBL4 use the standard CI-likerepressor, which is typically inactivated by SOS-response mediatedRecA-dependent autoproteolytic processing, phiMBL3 exhibits a C-terminallytruncated CI*-like repressor lacking the protease domain . Consequently, the phiMBL3repressor cannot be derepressed by RecA-mediated self-cleavage. Consistentwith these findings, a phylogenetic analysis revealed that the CI*-likerepressor of phiMBL3 clustered with Stl repressors of pathogenicityislands (SaPIs) which are typically derepressed by other proteinsinstead of being cleaved .Comparing the sequences of all prophage-likeelements in the genomeof S. aureus phage phiMBL3 by pyocyaninraised the question of how its producer P. aeruginosa might benefit from this selectivity. We speculated that a broadspectrum SOS-response inducing compound would also induce residentprophages in the genome of P. aeruginosa which wouldbe self-destructive.The selectiveinduction of P. aeruginosa. Indeed, while mitomycin C caused prophageinduction, pyocyanin had no such effect , pyocyanindid not lead to induction even at concentrations up to the MIC valueof 200 μM and in contrast even slightly reduced PFU counts inconcentration dependence (P. aeruginosa or E. coli. We next aimedto explore if induction of prophages significantly contributes tocell lysis. We thus compared the colony forming units (CFU) of S. aureus ATCC 6341 with the prophage-cured strain RN4220upon pyocyanin treatment. Strain ATCC 6341 showed significantly reducedviability at prophage-inducing pyocynanin concentrations comparedto RN4220. These results suggest that prophage induction may activelycontribute to killing of cells probably due to phage-related celldisruption and indicate that prophage induction may be a suitablestrategy for P. aeruginosa to controlpopulation density of competing bacteria . The mechanism responsible for the selectivityof pyocyanin consequently operates independently from the SOS-response.Pyocyanin-mediated prophage induction depends on high-level productionof reactive oxygen species and is controlled by the intracellularoxidation level. The truncated CI*-like repressor of phiMBL3 resemblesStl-repressors of SaPIs, which are known to be induced by multiplediverse and unrelated proteins of helper phages. It can thus be speculatedthat the repressor of phiMBL3 may be specifically derepressed in anoxidative cellular environment by binding of an oxidative stress orredox state-induced or -activated protein which still needs to bediscovered. In E. coli oxidative stress is knownto activate the transcription factor OxyR, which efficiently repressesprophage induction.38 This effect may beresponsible for the nonresponsiveness of Gram-negative bacteria topyocyanin. In addition, some Gram-negative bacteria have potent detoxificationmechanisms such as efflux pumps that can reduce effective exposureto pyocyanin.39 In a sense, species selectivitypossibly entails prophage selectivity, and since most bacteria harborprophages, secreting metabolites with nonselective activity wouldbackfire on their producers. P. aeruginosa may benefitfrom lysis of a subpopulation of a particular S. aureus strain but also from the cascade effect that phage production mayhave on other nonlysogenized competitors. Phage particles may eventrigger a maladaptive antiviral immune response that prevents clearanceof a bacterial pathogen and aid the infection process in mammalianhosts.40 Pyocyanin has many important biologicalfunctions including mediating cell death of P. aeruginosa during biofilm formation, promoting anaerobicsurvival, and acting as virulence factor against the human host.43 Our finding that pyocyanin also serves as a selective prophage induceradds to the long list of remarkable activities of this metabolite.Prophage induction mediated by the SOS-responsehas been shown,for example, for Vibrio dependingon cell density,21 and it was found thata peptide-based signal called arbitrium enables communication betweenlysogenic phages.23 Also Streptomyces metabolites have been described acting as a chemical defense systemto block replication of lytic phages via intercalating DNA.20Recent discoveries have increasingly contributed to a picture ofsmall molecules driving microbe–phage interactions within aspecies. For example, a quorum sensing signal was identified thatguides the lysogenic to lytic decision of We now demonstrated that microbial metabolitescan be potent cross-speciesprophage inducers and furthermore exhibit selectivity on a prophagelevel in polylysogenic hosts. Our results not only challenge the understandingof metabolite-mediated interactions within microbiota by adding anadditional layer of complexity but also open up an entirely new fieldfor manipulating these interactions. Selective prophage inducers couldallow exploitation of a built-in destruction mechanism of microbesleading to controlled lysis. Triggering lysogenic to lytic conversionin a selective way may allow active restructuring of microbial communitiesand may offer an alternative solution to phage therapy. On the otherhand, it also has not escaped our notice that the selective inductionof prophage-like sequences could be repurposed for the constructionof small molecule controlled molecular switches for synthetic biology.Pseudomonas aeruginosa is a trigger factor that hijacks the lysogenic to lytic switch ofa polylysogenic Staphylococcus aureus strain andleads to the selective production of only one of its prophages. Weprovide evidence that this potent and prophage-selective inductionis controlled by a mechanism that differs from the typical SOS-response.We have shown that pyocyanin produced by


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 higher Survival rates? The outcomes assessed were the overall survival rates in both techniques. The best evidence showed that there is no statistically significant difference between EVAR and OSR in survival rates. •Endovascular abdominal aortic aneurysm repair is inferior to open surgical repair regarding the secondary rupture rates.•Long term outcomes of the open surgical repair are better than the Endovascular repair.•Secondary rupture is more common in endovascular repair than the open surgical repair of abdominal aortic aneurysm. This fo2While discussing the management options of 65 years old patient with Infrarenal abdominal aortic aneurysm (AAA) of 6.5 cm, one of the junior doctors asked which has better long term survival rate (>5 year); open surgical repair (OSR) or endovascular abdominal aortic repair (EVAR)?••[Which modality of treatment has higher long term overall survival rates];•[EVAR or OSR]?Three Parts Question:3AEmbase 1974 to June 2021 using the OVID interface:B.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 [Survival rate].[AAA OR Abdominal Aortic Aneurysm]AND [Open repair OR Open surgical repair OR OSR] AND [EVAR OR Endovascular Repair] AND [Survival rate].•Inclusion criteria: all original articles that review Survival 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.4A total of 1741 papers were found using both search engines. We excluded 960 articles because they were irrelevant based on the titles and the abstracts. Seven hundred eighty-one full-text articles were screened and assessed for eligibility. From these, six papers were identified to provide the best evidence to answer the question. see 56EVAR is no being considered as standard treatment for AAA because of the initial promising results .However,In this article, we reviewed the best studies which compared the two modalities of AAA repair to evaluate which techniques have higher survival rates.Only one study in our review showed a statistically significant difference between EVAR and OSR in survival rate in favor of the OSR group; this study was conducted by Huang 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 Sch7According to the above articles, the best evidence shows no statistically significant difference in long-term overall survival rate among patients with open surgical repair of abdominal aortic aneurysm compared to endovascular repair.Ahmed Abdel Rahim (AA): Conducted the literature search and wrote the paper.Rashid Ibrahim (RI): Assisted in the literature search and Writing of paper.Lu Yao(LY): Editing of writing.Ahmed Khalf (AK): Assisted in writing of paper.Mohammed Ismail (MI): Assisted in the literature search and writing of paperEthical approval was not required.No source of funding.1. Name of the registry:2. Unique Identifying number or registration ID:3. Hyperlink to your specific registration (must be publicly accessible and will be checked):Ahmed Abdel Rahim.Ethics committee approval was not required as the study was review of previously done studies.No conflicts of interest.


Methanoperedenaceae was a predominant group under closed-circuit conditions.Information about sediment microbiota affected by sediment microbial fuel cells (SMFC) is limited. A laboratory-scale SMFC was applied to a eutrophic lake sediment under closed-circuit/open-circuit conditions. We analyzed the prokaryotes in the sediment adhering to the anode material. The archaeal family  Sediment microbial fuel cells (SMFC) can generate electrical energy using an anode embedded in the sediment and a cathode submerged in the overlying water . In thisThe SMFC column configurations have been described previously . BrieflyMethanoperedenaceae was the only group that showed a significant difference with the circuit condition , compared to OC conditions  (P < 0.005 by Student's t test). These data imply that this archaeal group may contribute to the bioelectrogenesis of the SMFC in eutrophic lake sediments.The archaeal family ondition . MethanoPRJNA767541 (The sequences were submitted to the NCBI Sequence Read Archive (SRA) under the BioProject accession number NA767541 .


Infectious respiratory-track pathogens are a common trigger of healthcare capacity strain, e.g. the COVID19 pandemic. Patient risk stratification models to identify low-risk patients can help improve patient care processes and allocate limited resources. Many existing deterioration indices are based entirely on structured data from the Electronic Health Record (EHR) and ignore important information from other data sources. However, chest radiographs have been demonstrated to be helpful in predicting the progress of respiratory diseases. We developed a joint EHR and chest x-ray (CXR) model method and applied it to identify low-risk COVID19+ patients within the first 48 hours of hospital admission. All COVID19+ patients admitted to a large urban hospital between March 2020 and February 2021 were included. We trained an image model using large public chest radiograph datasets and fine-tuned this model to predict acute dyspnea using a cohort from the same hospital. We then combined this image model with two existing EHR deterioration indices to predict the risk of a COVID19+ patient being intubated, receiving a nasal cannula, or being treated with a vasopressor. We evaluated models’ ability to identify low-risk patients by using the positive predictive value (PPV). The image-augmented deterioration index was able to identify 12% of 716 COVID-19+ patients as low risk with 0.95 positive predictive value in the first 48 hours of admission. In contrast, when used individually, the EHR and CXR models each identified roughly 3% of the patients with a PPV of 0.95.Predicting Low Risk PatientsAggregated predictions for COVID19 positive patients within the first 48 hours of admission, shown with exponential weight moving average and 95% CIs. Each plot shows the number of patients flagged as low-risk by lowest aggregated prediction and the resulting accuracy for that fraction of patients. The bottom plot compares the MCURES fused model to the MCURES model. The top plot compares the EDI fused model to the EDI model.Our multi-modal models were able to identify far more patients at low-risk of COVID19 deterioration than models trained on either modality alone. This indicates the importance of combining structured data with chest X-rays when creating a deterioration index performance for infectious respiratory-track diseases.All Authors: No reported disclosures


To the editor:Drug-related bradycardia (DRB) is a common conundrum in clinical practice and is often an adverse effect of a desired effect. However, it can result in multiple hospital admissions, particularly for older adults.Over a three-month period, we identified 100 hospitalised patients aged over 70 years with 2 or more documented episodes of bradycardia during admission . These constituted 4.32% of total admissions. Syncope was the most common presenting symptom and occurred in 23 patients. Causality assessment via Naranjo algorithm demonstrated a definite causal association between the administration of rate-limiting medications and bradycardia (score of 9) [Although our study did not report any in-hospital death, during the 12-month follow-up period 30 patients had deceased, 14 patients were re-admitted with DRB and 5 patients underwent permanent pacemaker implantation. Neither an admission with DRB or a background of AF were significant predictors of mortality.Patients initially diagnosed with AF often have a rapid ventricular response and require rate limiting medications such as beta-blockers and non-dihydropyridine calcium channel blockers drugs to mediate their heart rate As AF progresses there is electrical remodelling and changes in the expression of ion channels within the cardiomyocytes leading to myocardial fibrosis This in turn slows conduction through cardiomyocytes and leads to delayed ventricular response or “slow AF” This process occurs over many years and can remain clinically silent ,3 We susWithout pharmacovigilance older adults may continue taking rate-limiting drugs despite a gradual reduction in their heart rate. Another point to underscore, is that many older adults are underweight and sarcopenic  which can result in prescription errors based on weight and size. Caution should therefore be exercised when initiating and up-titrating rate-limiting medications in older patients, and those with AF should undergo regular review of their heart rate and ECG surveillance. Holter monitoring may be a valuable tool within in this context and should be routinely employed.