Durable left ventricular assist device therapy has improved survival in patients with advanced heart failure refractory to conventional medical therapy, although the readmission rates due to device-related comorbidities remain high. Left ventricular assist devices are designed to support a failing left ventricle through relief of congestion and improvement of cardiac output. However, many patients still have abnormal hemodynamics even though they may appear to be clinically stable. Furthermore, such abnormal hemodynamics are associated with an increased risk of future adverse events including recurrent heart failure, gastrointestinal bleeding, stroke, and pump thrombosis. Correction of residual hemodynamic derangements post-implantation may be a target in improving longitudinal clinical outcomes during left ventricular assist device support. Automatic and timely device speed adjustments considering a patients’ hemodynamic status  are potential improvements in forthcoming devices. Despite considerable improvement in available heart failure-specific medical therapies including beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, aldosterone antagonists, angiotensin receptor-neprilysin inhibitors, and arginine vasopressin type II receptor antagonists, morbidity and mortality in patients with advanced heart failure remain exceedingly high .In addition to mechanical circulatory support technologies including the intra-aortic balloon pump, extra-corporeal membrane oxygenation, and percutaneous axial-flow left ventricular assist device (LVAD), cardiac replacement therapy (heart transplantation and durable LVAD) remains the gold-standard therapy for those with refractory stage D heart failure . Given tLVAD therapy improves survival in patients with advanced heart failure compared to medical therapies alone ,5; howevLVADs correct hemodynamic derangements by mechanically unloading the failing left ventricle that decreases intra-cardiac pressure and subsequently increasing systemic circulation that increases total cardiac output. However, one report showed that many LVAD patients have abnormal hemodynamics despite appearing clinically stable in the ambulatory setting . FurtherDurable LVAD technology is improving, from para-corporeal models to the implantable and smaller iterations, including both pulsatile and continuous-flow types. Notably, the dominant types in the current era are implantable continuous-flow devices  12]. Th. Th12]. 2. Notably, we can measure directly or calculate various other hemodynamic parameters using right heart catheterization, as discussed later.Nevertheless, our group recently found that many LVAD patients had abnormal hemodynamics despite showing no apparent clinical symptomology . Here, wParticularly, many LVAD patients seem to have inappropriately elevated central venous pressure indicative of sub-clinical right heart failure ,14. LVADFor several reasons, we believe that invasive right heart catheterization should be routinely performed following LVAD implantation . First, Our team recently demonstrated that the presence of abnormal hemodynamics post-LVAD implantation, even without heart failure symptoms, was associated with future instances of clinical volume overload and heart failure recurrence . As one Optimal device positioning also affects the device’s ability to effectively unload the left ventricle, with malposition of the inflow cannula associated with an increased risk of future heart failure exacerbations . LateralBleeding, particularly gastrointestinal bleeding, is among the most common comorbidities during LVAD support with an estimated incidence of 25% . Some gaThe mechanism of gastrointestinal bleeding is multifactorial . In addiThe most apparent risk factor for LVAD-associated stroke is uncontrolled systemic blood pressure . This rePump thrombosis is one of the major causes of device malfunction that requires device exchange . AbnormaSeveral unique hemodynamic patterns vary by disease state including right heart failure, pulmonary hypertension, and aortic insufficiency.We should state at first that there is no comprehensive and consistently agreed-upon definition of right heart failure . Right hAs mentioned above, right heart failure remains a highly morbid complication of contemporary LVAD therapy. Despite the pump’s purpose to restore systemic perfusion in the failing heart by unloading the left ventricle, adverse right ventricular remodeling resulting from longstanding left ventricular failure is common and challenging to correct by durable mechanical circulatory support alone. Following LVAD implantation, right ventricular preload dramatically increases due to improved systemic circulation. The right ventricle, however, is often unprepared for this drastic increase in flow due to maladaptive structural changes from the afterload of a chronically failing left heart. As a result, right heart failure can become apparent both early and in later periods following LVAD implantation. Furthermore, a decrease in the size of the left ventricle due to mechanical unloading also facilitates a geometrical unbalance between the left and the right ventricle, resulting in further impairment of normal right ventricular contractile mechanics .Elevated central venous pressures in the setting of normal pulmonary capillary wedge pressure are one of the hallmarks of right heart failure and tend to be difficult to correct alone through mechanical unloading . Right hInvasive right heart catheterization provides the clinician valuable information regarding right ventricular performance. Pulmonary artery pulsatility index, which is calculated as a pulse pressure of the pulmonary artery divided by the central venous pressure, is a recently proposed index of right ventricular function , with a Many patients with advanced heart failure have secondary pulmonary (combined pre and post-capillary) hypertension due to chronically elevated left-sided filling pressures . HoweverAortic insufficiency is a unique and progressive comorbidity during long-term LVAD support. Continuous left ventricular unloading leads to aortic valve closure and pressure increases in the aortic root via the outflow graft. This can lead to valvular degeneration, and subsequent continuous and eccentric valvular regurgitation . Aortic The severity of aortic insufficiency is assessed usually using conventional color Doppler echocardiography for visual estimation. Accurate quantification is challenging given non-physiologic continuous and eccentric regurgitant flow. Our group recently proposed several methods to more accurately quantify the severity of aortic insufficiency .First, we can estimate the degree of aortic insufficiency using a device flow monitor, which is equipped in the HeartWare LVAD . This stSecond, we can quantify the severity of aortic insufficiency using Doppler echocardiography obtained at outflow graft  53]. Th. Th53]. As discussed above, abnormal hemodynamics are associated with various adverse clinical outcomes during LVAD support. Furthermore, there are several hemodynamically unique comorbidities during LVAD support which have unique and specific management strategies.2. We simultaneously perform echocardiography to assess for aortic valve opening, to understand the interventricular septum position, and to determine the presence of mitral valve regurgitation at each speed interval . It. It61]. The CardioMEMS device might have the potential to be utilized in LVAD patients to monitor and adjust device parameters in response to hemodynamic status . This isReDS is another promising tool to noninvasively estimate intra-thoracic fluid levels , which mThe HeartWare LVAD provides an estimated instantaneous flow waveform that shows insights into patients and device properties. For example, low pulsatility and low mean flow indicate hypovolemia, whereas low pulsatility and high mean flow let us detect suspected device thrombosis. High pulsatility and low mean flow might indicate continuous suction, whereas high pulsatility and high mean flow indicate volume overload. LVAD flow is determined by the pressure difference between the aorta and left ventricle at a fixed device speed. When aortic pressure is assumed to be constant at the diastole phase, LVAD flow is dependent on left ventricular pressure. When left ventricular pressure increases, LVAD flow often increases. Given this mechanism, pulmonary capillary wedge pressure can be estimated by the slope of LVAD flow at the end-diastolic phase  66]. We. We66]. Future advances in durable mechanical support may include a smart pump concept, which can automatically adjust device speed by continuously monitoring hemodynamic data points. For example, a novel smart pump might automatically measure the HeartWare LVAD flow slope and adjust its rotational speed considering estimated intra-cardiac pressure . If the Despite durable LVAD support, many patients can have abnormal hemodynamics due to a variety of clinical conditions even when clinically stable. LVAD therapy has improved survival in patients with advanced heart failure, though considerable limitations remain including unacceptably high readmission rates due to these various comorbidities, including volume overload and hemocompatibility-related adverse events. Assessment and optimization of hemodynamics might be one of the modifiable targets which could reduce the burden of these common post-implant complications. Interventions to optimize the hemodynamic status by adjustments of device speed and medications might improve clinical outcomes, though further large-scale prospective randomized control trials are needed to study these interventions. In the interim, noninvasive methods that estimate hemodynamics, including CardioMEMS, ReDS, and HartWare LVAD waveform analyses, may prove to be useful in more precisely guiding daily LVAD management.


Previous cross-sectional research suggests that age-related decreases in Rapid-Eye Movement (REM) sleep may contribute to poorer cognitive functioning (CF); however, few studies have examined the relationship at the intraindividual level by measuring habitual sleep over multiple days. Applying a 14-day daily diary design, the current study examines the dynamic relationship between REM sleep and CF in 69 healthy older adults . A Fitbit device provided actigraphy indices of REM sleep , while CF was measured four times daily on a smartphone via ambulatory cognitive tests that captured processing speed and working memory. This research addressed the following questions: At the within-person level, are fluctuations in quantity of REM sleep associated with fluctuations in next day cognitive measures across days? Do individuals who spend more time in REM sleep on average, perform better on cognitive tests than adults who spend less time in REM sleep? A series of multilevel models were fit to examine the extent to which each index of sleep accounted for daily fluctuations in performance on next day cognitive tests. Results indicated that during nights when individuals had more REM sleep minutes than was typical, they performed better on the working memory task the next morning . These results highlight the impact of REM sleep on CF, and further research may allow for targeted interventions for earlier treatment of sleep-related cognitive impairment.


The house acts as both an environment of care and a vehicle to financially potentiate long-term community-based support. While housing can empower a diverse set of options for a person-centered aging process, inadequate housing can also impede healthy aging in the community. This symposium teases out the nodes where housing acts to benefit or limit safe community-based aging. The first paper in this symposium, Homeownership Among Older Adults, describes typologies of older adult homeownership and sensitively highlights trends, disparities and important considerations of homeownership in later life. The next two papers take these older adults and explores situations where their housing acts as an asset or as a burden. Identifying Cost Burdened Older Adults acknowledges that housing cost burdens look different for older adults than younger cohorts. A more precise definition of older adult housing cost burden is proposed to help researchers and policymakers better synthesize the complex relationships between older adult housing and their long-term care decisions. The Long-Term Care Financing Challenge then explores the role of home equity in expanding the community-based long-term care choice set for older adults. This paper demonstrates benefits  in home equity and suggests policy implications moving forward. Finally, Cardiometabolic Risk Among Older Renters and Homeowners disentangles the relationship between housing and health by demonstrating health disparities that are associated with housing tenure, conditions and affordability. Taken together, this symposium explores the complex and multidirectional relationships between housing, long-term care and older adult health.


Loneliness is a distressing yet adaptive emotional experience that alerts us to socially re-engage. However, loneliness can also lead to social withdrawal and isolation. To reconcile the seemingly contradictory consequences of loneliness, we unpack the timing of the underlying processes by distinguishing between the roles of state loneliness  and trait loneliness  in predicting social re-engagement. Using ten days of electronic daily assessments from 95 older adults , initial findings indicate that trait loneliness moderates time-varying associations between state loneliness and prosocial behavior: On days of elevated state loneliness, older adults low in trait loneliness report increases in prosocial behavior, whereas older adults high in trait loneliness show decreases in prosocial behavior. Findings suggest that transient loneliness may motivate older adults to actively re-engage with others; chronic loneliness may undermine such adaptive responses.


Emerging data from epidemiological studies have confirmed elevated prevalence rates for mental health conditions among the lesbian, gay, bisexual and transgender (LGBT) populations. An estimated 2.8% of Asian Americans identify as LGBT and 26% of Asian LGBT are 40 years or older. This study analyzed the California Health Interview Survey to examine differences in psychological distress between LGBT and non-LGBT older Asian Americans, and further evaluated the role of discrimination in medical care and intimate violence on psychological distress. Regression results showed older LGBT Asians had a higher psychological distress score compared to non-LGBT Asians. After adjusting for discrimination or violence, this association no longer existed. Experiencing discrimination in medical care and intimate violence were associated with higher levels of psychological stress. This study increases our knowledge of mental health among older Asian LGBT, enhancing our ability to design culturally-targeted and trauma-informed psychosocial interventions to improve outcomes in this population.


Existing evidence suggests that individuals’ subjective experience of cognitive decline may be a risk state for dementia. However, whether self-awareness of positive changes confer cognitive protection is unknown. We examined the extent to which awareness of positive (AARC gains) and negative (AARC losses) age-related changes explains variability in objective cognitive performance in a sample of 6,231 UK residents  without cognitive impairment. We tested a structural equation model with AARC gains and losses as predictors of cognitive performance and depressive symptoms as a mediator of the association of AARC losses with cognitive performance. The model fit the data well. The correlation between AARC gains and losses was negligible, yet higher levels of both AARC gains and losses predicted poorer cognitive scores. Hence, higher AARC gains did not confer cognitive protection. This unexpected pattern of results underscores the complexity of mapping individuals’ awareness onto objective outcomes.


Cancer cells directly control nutrient uptake and utilization in a different manner from that of normal cells. These metabolic changes drive growth, proliferation of cancer cells as well as their ability to develop resistance to traditional therapies. We review published studies with pre-clinical models, showing the essential roles of lipid metabolism in anticancer drug resistance. We also discuss how changes in cellular lipid metabolism contribute to the acquisition of drug resistance and the new therapeutic opportunities to target lipid metabolism for treating drug resistant cancers.Metabolic reprogramming is crucial to respond to cancer cell requirements during tumor development. In the last decade, metabolic alterations have been shown to modulate cancer cells’ sensitivity to chemotherapeutic agents including conventional and targeted therapies. Recently, it became apparent that changes in lipid metabolism represent important mediators of resistance to anticancer agents. In this review, we highlight changes in lipid metabolism associated with therapy resistance, their significance and how dysregulated lipid metabolism could be exploited to overcome anticancer drug resistance. Many oncogenic mutations resulting in the aberrant activation of several signaling pathways can reprogram cancer cell metabolism to such an extent that metabolic reprogramming is considered one of the major hallmarks of cancer . Cancer i) overproduction of neutral lipids such as triacylglycerols stored in LD that accumulate in cancer to provide a reserve of energy; (ii) production of phospholipids is used to build cancer cell membranes to satisfy the increased demand for cancer proliferation. Moreover, phospholipids also act as lipid messengers and intracellular signaling molecules in cancer . Among r review . Particur review ,17. Humar review . Orlistar review . Besidesr review . Many enr review .Secondly, apart from lipogenesis, it was observed that FAs, either from extracellular sources or mobilized from internal lipid stores, can be oxidized in cancer cell mitochondria B. Under Furthermore, lipolysis and lipogenesis may coexist in cancer cells . Lipid mEmerging evidence also suggest that dysregulated lipid metabolism could play a role in resistance to anticancer drugs. Furthermore, the dependence of cancer cells on aberrant lipid metabolism could point to lipid metabolism being a potential source of new attractive targets to eradicate cancer cells. This review highlights the role and mechanisms of lipid metabolism reprogramming induced by anticancer drugs during the development of chemoresistance in cancer cells. In addition, we discuss the potential of reversing chemoresistance via lipid metabolism regulation.It is now well-established that lipid metabolism changes are associated with resistance to conventional chemotherapies and targeted therapies in several cancers. Lipid metabolic reprogramming of resistant cancer cells includes both changes in de novo lipogenic synthesis and/or lipolytic pathway. With some exceptions , cancer Secondly, changes in the lipid metabolism of resistant cells vary depending on the environment and cellular context. Thus, radiation resistance was associated with a significant increase in CPT1A-dependent lipolysis in nasopharyngeal carcinoma whereas radiation resistance was linked to de novo lipogenesis in head and neck squamous carcinoma ,51. MechOverall, these data indicate that changes in lipid metabolism of resistant cells are treatment specific but also environmental and cellular context-dependent resulting in a high heterogeneity of lipid metabolisms.Of note, it is interesting to stress out that lipid metabolism changes, de novo lipogenesis or lipolysis, can be unveiled upon anticancer drug exposure. Comparison of paired NSCLC tumor tissues from patients before and after Gefitinib treatment revealed a significant increase in lipid droplet content and in SCD1 expression . Upon 5-Firstly, several studies suggested that aberrant lipid metabolism could be seen as metabolic shift allowing cancer cells to adapt to treatment-induced cellular stress. Almost all anticancer drugs including conventional chemotherapies and targeted therapies induce cancer cell stress that can ultimately lead to cell death. It was reported that several cellular stressors like lack of nutrients, high levels of reactive oxygen species (ROS) promote de novo lipogenesis . Thus, lSecondly, apart from an adaptive process, cancer cell exposure to anticancer drugs can result in an enrichment of a pre-existing cellular subpopulation characterized by aberrant lipid metabolism. According to this hypothesis, lipid metabolism is a metabolic state allowing a sub-population of cancer cells to escape the effects of anticancer drugs when other cancer cells die. This subpopulation could be represented by cancer stem cells (CSCs), a highly resistant subset of cancer cells. Indeed, it is well established that even if a successful cancer therapy abolishes the bulk of tumor cells, CSCs can survive to standard cancer treatments and are at the core of clinical relapse . InteresIn many preclinical models, lipid metabolism inhibition can reverse the resistance of cancer cells to cancer drugs suggesting that lipid metabolism may play a role in drug resistance. The question is how can lipid metabolic reprogramming contribute to anticancer drug resistance?The oxidative stress induced by anticancer drugs result in peroxidation of lipid membranes, oxidative modifications of proteins and DNA. Doxorubicin, which possesses an anthracycline skeleton, generates ROS leading to DNA damage followed by anticancer activity. Likewise, vinca alkaloids increase intracellular ROS production by depleting the intracellular GSH causing DNA damages. Changes in lipid metabolism elicit a cytoprotective response to oxidative stress in several different ways: (i) lipid droplets decrease ROS toxicity thereby increasing cancer cell survival  ProductiLipid droplet accumulation was evidenced to support colorectal cancer resistance to 5-fluorouracil (5-Fu) and oxaliplatin by inhibiting ER stress . Indeed,Overexpression of FAS, the key enzyme of de novo lipogenesis pathway, triggers cancer resistance to genotoxic drugs by increasing DNA repair . MechaniTargeted therapies such as MAPK inhibitors inhibit glucose uptake and antiglycolytic effects triggering energy stress conditions contributing to the promotion of cancer cell death (see above). Acetyl-CoA derived from fatty acid oxidation can fuel the mitochondrial TCA cycle to reduce energetic stress. This metabolic shift towards FAO, is often orchestrated by the AMP-dependent protein kinase (AMPK). Activation of AMPK in response to low energy levels boosts energy production through a mitochondrial FAO increase  and therLipid metabolism can also interfere with the process of apoptotic cell death induced by anticancer drugs through two distinct mechanisms: (i) LDs were shown to remove apoptosis-related proteins, such as BCl-2 family members, from mitochondria by direct contact between outer mitochondrial membrane and lipid droplet surface . This pr+ CSC content in the MCF7 breast cancer cell line [A large body of evidence indicates that human cancers emerge from CSCs, which are intrinsically resistant to many anticancer treatments including conventional chemotherapies, targeted drugs and radiation. CSCs are also the main source of cancer relapse. Interestingly, lipid metabolic reprogramming contributes to CSCs expansion and survival therefore enhancing the occurrence of chemoresistance . Severalell line . Activatell line  converseell line . HMG-CoAell line ,94,95,96ell line . Similarell line .Overall, these observations identify the rewiring of lipid metabolism as a novel and important mechanism of adaptive resistance to anticancer drugs.As detailed above, recent studies have shown that cancer cells develop changes in lipid metabolism, which is different from that of non-proliferative differentiated cells. These observations open up new avenues for the exploitation of lipid metabolism as a source of new therapeutic targets. Natural and synthetic agents that affect lipid metabolism in cancer is a rapidly growing field that was recently reviewed elsewhere . The focNumerous pharmacological inhibitors have been developed for almost all enzymes of lipid metabolism and some compounds are used in clinical trials in association with conventional therapies . CombinaBesides, due to the role of lipid metabolism in the acquisition of treatment resistance, targeting lipid metabolism could be used to re-sensitize cancer cells to standard treatments. FAS inhibitors have shown in-vivo and in-vitro anticancer effects and are also responsible for re-sensitization of cancer cells to conventional therapy ,106,107.One major interest in lipid targeting for cancer treatment is the possibility of using existing clinically-approved drugs originally developed for other lipid-related diseases. This drug repositioning in oncology has the main advantage of improving safety and reducing costs. Besides the anti-obesity drug, orlistat (see above), statins represent a classic example of drug repositioning in oncology. Statins are currently the most efficient drugs to reduce circulating cholesterol, with few side effects including muscle pain and occasionally liver inflammation, and thereby are used in preventing the development of cardiovascular diseases . MoleculBased on preclinical data presented above, combination therapy consisting of standard anticancer therapies and lipid metabolism inhibitors would be effective for treating resistant cancers.Lipid metabolism plays a central role in cancer resistance, not only via an increased availability of lipids conferred by adipocyte environment but also through profound changes in cancer cell lipid metabolism. It is particularly interesting to note that CSCs, cells that are known to be at the center of resistance mechanisms and relapse, have an increased dependence on lipid metabolism. This could offer a very large number of potential targets, as reported in this review. Changes in the lipid metabolism of cancer cells has been overlooked since conventional 2D cell culture is unable to recapitulate the tumor environment. Moreover, conventional culture medium does not recapitulate normal fatty acid environment as reported by Else . Optimiz


Teaching point: Hoarseness is a common condition that can be the initial symptom of cardiovascular disorder. A 76-year-old women who quitted smoking ten years earlier presented with recent-onset hoarseness of the voice. She had history of pulmonary commissurotomy. Fiberoptic laryngoscopy revealed paramedian left vocal cord paralysis. Chest computed tomography showed hiatus hernia and left pulmonary artery aneurysm (largest diameter 66 mm) Figures  and 2 wiThe recurrent laryngeal nerves originate from the vagus nerves at different levels. The right recurrent laryngeal nerve exits anterior to the right subclavian artery and runs underneath and behind it. On the left side, the recurrent laryngeal nerve leaves the vagus nerve on the anterior surface of the aortic arch, running inferiorly around it through the aortopulmonary window posterior to the ligamentum arteriosum. Then they both rise up between the trachea and esophagus to reach larynx and innervate the intrinsic laryngeal muscles, except the cricothyroid muscle. Because of its longer course in mediastinum, the left recurrent laryngeal nerve is more vulnerable . This neThere are various mediastinal causes for vocal cord paralysis including surgical or iatrogenic injuries, traumatic lesions, inflammatory or infectious diseases, amyloidosis, tumours, and cardiovascular diseases. Ortner syndrome  refers to hoarseness resulting from left recurrent laryngeal nerve paralysis caused by cardiovascular disease . It was Pulmonary artery aneurysms are rare, predominantly involving main pulmonary arteries, and may be idiopathic or result from congenital  or acquired  causes. It has been reported that early pulmonary valve commissurotomy may induce pulmonary artery aneurysm development due to eccentric right ventricular outflow jet.This case emphasizes the need to investigate neck and chest when looking for a causative lesion to hoarseness.


Anabaena sp. ATCC 33047 is a marine, heterocyst forming, nitrogen fixing cyanobacteria with a very short doubling time of 3.8 h. We developed a comprehensive genome-scale metabolic (GSM) model, iAnC892, for this organism using annotations and content obtained from multiple databases. iAnC892 describes both the vegetative and heterocyst cell types found in the filaments of Anabaena sp. ATCC 33047. iAnC892 includes 953 unique reactions and accounts for the annotation of 892 genes. Comparison of iAnC892 reaction content with the GSM of Anabaena sp. PCC 7120 revealed that there are 109 reactions including uptake hydrogenase, pyruvate decarboxylase, and pyruvate-formate lyase unique to iAnC892. iAnC892 enabled the analysis of energy production pathways in the heterocyst by allowing the cell specific deactivation of light dependent electron transport chain and glucose-6-phosphate metabolizing pathways. The analysis revealed the importance of light dependent electron transport in generating ATP and NADPH at the required ratio for optimal N2 fixation. When used alongside the strain design algorithm, OptForce, iAnC892 recapitulated several of the experimentally successful genetic intervention strategies that over produced valerolactam and caprolactam precursors.Nitrogen fixing-cyanobacteria can significantly improve the economic feasibility of cyanobacterial production processes by eliminating the requirement for reduced nitrogen.  As production hosts, cyanobacteria have several advantages over eukaryotic plants and algae, including faster growth and higher photosynthetic efficiency 68]. The ming FVA . Unfortubacteria . Among tna 33047  was usedg strain . The fluiAnC892, for the fast-growing, N2-fixing cyanobacteria, Anabaena 33047 by pooling together annotation information from diverse databases. Because Anabaena 33047 forms heterocysts under diazotrophic conditions, the iAnC892 model featured two super-compartments: vegetative cell and heterocyst. iAnC892 was able to accurately capture several aspects of the diazotrophic metabolism of heterocyst forming cyanobacteria. Reaction content comparison with Anabaena 7120 and Anabaena 29413 indicated that iAnC892 is different from these models in terms of its reaction content. Cell specific shutdown of heterocyst-LETC revealed its importance in generating ATP and NADPH at ratios optimal for N2 fixation. Similar analysis of heterocyst central carbon metabolism revealed the existence of alternative routes other than PPP that can supply reducing equivalents for N2 fixation. The usefulness of iAnC892 was further tested by using it alongside OptForce to predict genetic interventions for overproduction of valerolactam and caprolactam. The study recapitulated several of the experimentally successful strategies. Further improvement in predictions can be achieved by using flux distributions specifically generated for Anabaena 33047. Availability of species-specific flux distribution would also help pin down exchanges between vegetative cell and heterocysts which would provide a clearer picture of the energy production pathways active in the heterocyst.In this study we constructed a comprehensive GSM model,


Assessment of metabolic cost as a metric for human performance has expanded across various fields within the scientific, clinical, and engineering communities. As an alternative to measuring metabolic cost experimentally, musculoskeletal models incorporating metabolic cost models have been developed. However, to utilize these models for practical applications, the accuracy of their metabolic cost predictions requires improvement. Previous studies have reported the benefits of using personalized musculoskeletal models for various applications, yet no study has evaluated how model personalization affects metabolic cost estimation. This study investigated the effect of musculoskeletal model personalization on estimates of metabolic cost of transport (CoT) during post-stroke walking using three commonly used metabolic cost models. We analyzed walking data previously collected from two male stroke survivors with right-sided hemiparesis. The three metabolic cost models were implemented within three musculoskeletal modeling approaches involving different levels of personalization. The first approach used a scaled generic OpenSim model and found muscle activations via static optimization (SOGen). The second approach used a personalized electromyographic (EMG)-driven musculoskeletal model with personalized functional axes but found muscle activations via static optimization . The third approach used the same personalized EMG-driven model but calculated muscle activations directly from EMG data . For each approach, the muscle activation estimates were used to calculate each subject’s CoT at different gait speeds using three metabolic cost models . The cal Metabolic cost has been used to evaluate human performance during daily activities such as walking  and athlin silico. Specifically, within the field of exoskeleton design, musculoskeletal models can eliminate the time and expense of iteratively designing and building physical prototypes. With advances in computational biomechanics, musculoskeletal models incorporating metabolic cost models have emerged as tools to estimate metabolic cost. These tools have been used to predict human movement and response to mechanical interventions . AlthougPrevious studies that estimated metabolic cost during walking have focused on using scaled generic musculoskeletal models. However, several studies have reported that personalization of anatomical and physiological characteristics of a musculoskeletal model can influence prediction of muscle forces, joint moments, and novel movements, factors that also play a role in metabolic cost calculations. This study evaluated the influence of musculoskeletal model personalization on metabolic cost estimates of walking post-stroke. To evaluate the physical realism of different metabolic cost modeling methods, we compared metabolic cost estimates to trends reported in the literature for individuals post-stroke. Experimental walking data collected from two male stroke survivors–one high functioning and one low functioning–were used as inputs to the metabolic cost analyses see , 2008.tf Hz (tf is the period of the gait cycle being processed (tf Hz) using a fourth-order zero-phase lag Butterworth filter. EMG amplitudes for each muscle were normalized to the maximum value over all trials and resampled to 101 time points per gait cycle, as described in The experimental data were processed using standard methods. The ground reaction and marker motion data were low-pass filtered using a fourth-order zero-phase lag Butterworth filter with a cut-off frequency of 7/tf Hz , where trocessed . On averA generic full-body OpenSim musculoskeletal model  served alsqnonlin algorithm, which iteratively ran OpenSim Inverse Kinematics analyses to calculate marker location errors.Personalization of the joint functional axes for the hip, knee, and ankle of each leg was performed by following a two-step process. First, the geometry of the generic OpenSim model was scaled to match the dimensions of each subject using the OpenSim Scale Model tool and the static standing trial data. Second, marker positions and functional axes of the model’s lower body joints were personalized as described in Experimental data from ten gait trials collected at each available walking speed were used to calibrate an EMG-driven model of both legs for each subject. Before performing EMG-driven model calibration, we analyzed marker data from each gait trial using the OpenSim Inverse Kinematics tool to generate joint angle trajectories. The OpenSim Inverse Dynamics tool was then used to calculate the joint moments produced by muscle forces. Next, a surrogate model of each subject’s musculoskeletal geometry was generated to allow the EMG-driven model to modify musculoskeletal geometry , 2017. Tfmincon algorithm with sequential quadratic programming, we adjusted the model parameter values to best match calculated experimental inverse dynamic joint moments and published passive joint moments , Hill-type muscle-tendon model parameters , and surrogate musculoskeletal geometry parameters. Using Matlab’s  moments . In addi moments , S2. A dTo evaluate the extent to which model personalization affects estimated metabolic cost, we developed three musculoskeletal models for each subject with varying levels of personalization. The least personalized model was a scaled generic OpenSim model where muscle activations were calculated via static optimization using quadratic programming (SOGen) . The intTo evaluate the physical realism of each musculoskeletal model/metabolic cost model combination, we identified five experimental trends in the literature for how CoT varies as a function of other clinically relevant quantities for individuals post-stroke. The first three quantities were step length asymmetry, stance time asymmetry, and double-support time asymmetry, all of which have been reported to increase as the CoT increases . The twoWe performed statistical analyses to evaluate whether trends in CoT as a function of the five quantities described above were different between each musculoskeletal model/metabolic cost model combination and the experimental data published in p-values tended to increase as the level of musculoskeletal model personalization increased, with the EMGCal musculoskeletal model generally exhibiting the largest p-values and thus the greatest statistical similarity to experimental measurements. In contrast, the p-values tended to be comparable across the three levels of musculoskeletal model personalization.The ability to predict CoT trends consistent with experimental measurements varied across the nine modeling combinations –5. Overap-values < 0.05). However, when absolute values of y-intercept differences were calculated , and the subject provided written informed consent prior to participation.CP and BF performed the experiments. MA performed all model personalization tasks, prepared the figures, and drafted the manuscript. MA and MS analyzed the data. MA, MS, and BF interpreted the results of analyses. All authors revised the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Aging is a major risk factor for chronic diseases and is directly linked to increasing mortality and healthcare costs worldwide. A key contributing factor to the aging process is a loss of stem/progenitor cell function which leads to a dysregulated tissue microenvironment and reduced repair/regeneration . Over thThe bone marrow is an important reservoir of stem/progenitor cells which cross-talk with peripheral organs to help maintain tissue function. Hematopoietic stem/progenitor cells (HSCs) are responsible for producing blood cells throughout life and these downstream cells play an active role in maintaining tissue homeostasis. With aging reduced function of bone marrow cells correlates with dysfunction of peripheral organs. For example, the decline in immune function with age, referred to as immuno-senescence, contributes to the accumulation of senescent cells, persistent low grade inflammation, and reduced responses to injury . The bon+ bone marrow stem cells and examined 4 months later to allow cross talk between the bone marrow and heart. Young bone marrow reconstitution rejuvenated cardiac endothelial cells which contributed to improved repair and better outcome following myocardial infarction. Mechanistically, young cells which migrated to the heart expressed more Cxcl12 and Vegf, key cytokines involved in angiogenic responses. This correlated with greater expression of CXCR4 and phospho-AKT in resident cardiac endothelial cells isolated from mice receiving young vs. old bone marrow. In addition to improved angiogenesis, our lab has shown that rejuvenation using reconstitution of young cells improves multiple repair processes. Young bone marrow cell transplantation increases the proliferation of resident cardiac cells [We recently utilized this bone marrow rejuvenation approach to study the effect aging has on the repair processes initiated post-myocardial infarction . Aged miac cells , increasac cells , and enhac cells . TogetheBeyond cardiac repair, we have shown that bone marrow cells interact with other tissues and that bone marrow rejuvenation can benefit multiple organ systems. Reconstituting aged mice with young cells leads to the repopulation of the retina with young bone marrow derived microglia . Within Together our studies as well as studies by others demonstrate that introducing young bone marrow into aged mice is an effective rejuvenation strategy with systemic benefits . Bone ma


The journal retracts the article, Dinitrosopiperazine-Mediated Phosphorylated-Proteins Are Involved in Nasopharyngeal Carcinoma Metastasis  cited abFollowing publication, concerns were brought to the attention of the publisher regarding the figures. Some stained tissue pictures in Figure 6  are duplWe apologize to our readership that this went undetected until now.


Bipolar disorder (BD) is a complex and serious psychiatric disorder characterized by mood dysregulation difficulties (American Psychiatric Association Emotion-related urgency (hereto referred as ERU) is defined as a tendency to act rashly in the context of extreme emotions, including trouble inhibiting impulses and risk-taking behaviors (e.g., Cyders and Smith negative urgency (defined as the tendency to behave rashly during extreme negative emotions; e.g., Whiteside and Lynam positive urgency (defined as the tendency to behave rashly during extreme positive emotions; Cyders This brief letter suggests the importance of considering impulsivity during mixed states. Both negative and positive ERU have been implicated in BD (Giovanelli et al. We suggest increased investigation into transdiagnostic presentations and clinical implications of ERU. Indeed, recent recognition of mixed features also occurring in the context of major depressive disorders underscores the important transdiagnostic utility of ERU across mood disorders. We suggest three key areas for future research. First, it will be important to develop well-validated assessment tools to measure mixed-mood ERU across self-report and clinician-rated instrument domains. Second, it will be important to carefully assess the maladaptive behaviors that may predict, and result from, ERU during mixed states and differentiate those from more general risk-taking behavior. Third, future research should carefully consider lifespan approaches that consider ERU in the context of BD onset, risk and recurrence at critical developmental junctures. We believe the time is ripe to call greater attention to examining risky and potentially fatal consequences of impulsivity during strong and co-occurring negative and positive emotion states.


Sepsis survivorship is associated with cognitive decline and complex post-acute care needs. Family caregivers may be unprepared to manage these needs, resulting in decline or no improvement in patient outcomes. Using a national dataset of Medicare beneficiaries who were discharged from the hospital for sepsis and received post-acute HHC between 2013 and 2014 , we examined the relationship between unmet caregiving needs and improvement or decline in cognitive functioning. Multivariate logistic regression was used to determine associations between unmet caregiving needs at the start of HHC and changes in cognitive functioning. Unmet caregiving needs included seven items from the start of care Outcome and Assessment Information Set (OASIS). Changes in cognitive functioning were measured using the start of care and discharge OASIS assessments. Twenty-four percent of patients either declined or did not improve in cognitive functioning from HHC admission to discharge, with variation seen by unmet need type. Sepsis survivors with unmet caregiving needs for activities of daily living assistance , medication assistance , and supervision and safety assistance  were more likely to decline or not improve in cognitive functioning, even after accounting for clinical and demographic characteristics. Older sepsis survivors with both cognitive impairment and unmet caregiving needs in the post-acute HHC setting are at high-risk for worsening cognition. Alerting the care team of cognitively impaired sepsis survivors with unmet caregiving needs may trigger evidence-based strategies to enhance caregiver training and reduce unmet caregiving needs.


Prior studies suggesting associations between cortical brain areas and gait speed has been largely cross-sectional and limited to one modality neuroimaging. Using machine learning from 506 cognitively normal BLSA participants aged 55+ who had repeated measures of brain volumes, diffusion tensor imaging (DTI), and gait speed, we examined multimodal neuroimaging predictors of gait decline, accounting for demographics, body composition, and grip strength. Significant predictors of gait decline included changes in volumes and DTI measures of gray matter in selected frontal, parietal, temporal, and subcortical areas, as well as white matter changes in both fractional anisotropy and diffusivity of tracts connecting frontal areas to subcortical motor areas. This predictive model highlights the importance of atrophy and microstructural deterioration in selected frontal and subcortical motor areas in predicting gait speed decline.


C. elegans. As shown in et al. 1986). Serotonin and Gao signaling, which regulate egg laying behavior, can also signal to inhibit defecation . Because evidence shows that both the egg-laying active state and the defecation motor program (DMP) are both linked to changes in forward and reverse locomotion , we reasoned there may be a similar relationship between expulsive behaviors that drive either egg laying or defecation. Our experiments document an association between HSN Ca2+ activity and a reduced frequency of defecation (Ravi and Collins 2019) [See accompanying microPub Ravi and Collins (I) 2019]. Animals lacking HSNs have a reduced defecation frequency (Garcia and Collins 2019) [See accompanying microPub Garcia and Collins (II) 2019]. We hypothesize that egg-laying and defecation behaviors are coordinated because they use the same internal hydrostatic pressure to drive expulsion of uterine or intestinal contents, respectively.We have identified a relationship between egg-laying and defecation behaviors in et al. 2002; Gilpin et al. 2015; Fechner et al. 2018), releasing waste about once per minute and ~3-5 fertilized eggs (~20 pL each) about every 20 minutes . During defecation, sequential activity of the anterior and posterior body wall muscles contracts the animal, increasing internal pressure that drives expulsion of liquid waste through the anus . Mutations that eliminate the defecation motor program still expel gut contents at much reduced frequency. This is thought to be caused by a gradual accumulation of internal pressure by ongoing pharyngeal pumping of food that eventually ejects waste through the anus independent of circuit activity or muscle contractility (Avery and Thomas 1997).Worms continuously internalize bacterial food via pumping of a muscular pharynx . Animals lacking HSNs still enter active states with strong vulval muscle contractions driving release of embryos which additionally supports this model . Electrical silencing of the postsynaptic muscles renders animals egg-laying defective with embryos often hatching inside the mother . Unlike gut contents which are more fluid, fertilized embryos are more mechanically rigid, requiring full opening of the vulva for efficient release . We propose that changes in the internal hydrostatic pressure that accompany food consumption and embryo production activate mechanoreceptors that facilitate the onset of defecation and egg-laying behaviors. As animals age, they continue to eat and grow larger, but their defecation frequency decreases . Egg laying frequency also increases with age for as long as animals have sufficient sperm for oocyte fertilization . This increase in egg laying in older adults reflects both an increase in the number of eggs expelled with each vulval opening and longer active behavior states. We propose that the timing of expulsive behaviors including defecation and egg laying is regulated by sensory mechanisms that detect changes in internal pressure and/or stretch to maintain homeostasis. Feedback of successful egg laying might also signal to the germ line to ensure the continued production of oocytes for fertilization.Our recent data suggest egg-laying behavior is regulated by a stretch-dependent homeostat. Feedback from embryo accumulation in the uterus activates the postsynaptic muscles which drives burst-firing in the presynaptic HSNs as visualized by Ca


Stroke is a devastating condition characterized by widespread cell death after disruption of blood flow to the brain. The poor regenerative capacity of neural cells limits substantial recovery and prolongs disruptive sequelae. Current therapeutic options are limited and do not adequately address the underlying mitochondrial dysfunction caused by the stroke. These same mitochondrial impairments that result from acute cerebral ischemia are also present in retinal ischemia. In both cases, sufficient mitochondrial activity is necessary for cell survival, and while astrocytes are able to transfer mitochondria to damaged tissues to rescue them, they do not have the capacity to completely repair damaged tissues. Therefore, it is essential to investigate this mitochondrial transfer pathway as a target of future therapeutic strategies. In this review, we examine the current literature pertinent to mitochondrial repair in stroke, with an emphasis on stem cells as a source of healthy mitochondria. Stem cells are a compelling cell type to study in this context, as their ability to mitigate stroke-induced damage through non-mitochondrial mechanisms is well established. Thus, we will focus on the latest preclinical research relevant to mitochondria-based mechanisms in the treatment of cerebral and retinal ischemia and consider which stem cells are ideally suited for this purpose. Stroke is currently the fifth leading cause of death in the United States and can cause disabling neurological deficits including cognitive impairment, hemiparesis, sensory disturbance, and aphasia . StudiesThe ischemic cascade  triggereMitochondrial dysfunction plays a key role in the pathological progression of ischemic stroke . MitochoThe body has multiple mechanisms to combat oxidative stress and clear damaged mitochondria. Cells can sequester functional mitochondria while degrading dysfunctional mitochondria via mitophagy ,16. In aThe discovery that stem cells can replace dysfunctional mitochondria in damaged cells has primed the field of stroke therapy for critical improvements in treatment outcomes . In the The ideal cell source to leverage the therapeutic benefits of mitochondrial transfer is bone marrow-derived mesenchymal stem cells (BM-MSCs). This cell type gives rise to endothelial progenitor cells (EPCs), which produce nearly all of the endothelial cells in the body . In the An in vitro stroke model proved that EPCs could successfully discharge their mitochondria . ProteinThe next step in confirming a mechanism of EPC-mediated mitochondria transfer is to assess whether endothelial cells take up these extracellular mitochondria and whether this would aid the recipient cell. In that same study, confocal microscopy demonstrated evidence of mitochondria-containing, EPC-derived extracellular vesicles within endothelial cells in the cerebral vasculature . TherefoAlthough at this point there is considerable evidence for the role of EPCs in restoring mitochondrial function via a transfer mechanism, there was still much uncertainty surrounding the benefits of stem cell mitochondrial therapy. Additional studies on EPC-derived mitochondria addressed these concerns. FACS-assisted proteome analysis of OGD-exposed brain endothelial cells reveals that uptake of EPC-derived mitochondria enhances the production of angiogenic and BBB proteins, including Serpin E1, plasminogen, FGF-4, and bFGF . These fThe ischemic conditions brought about by stroke damage endothelial cells and predispose them towards undergoing intrinsic pathway apoptosis, which is mediated by mitochondrial dysfunction . IntegraImportantly, astrocytes can also transfer their mitochondria to damaged neurons but do so in a transient fashion. Thus, they do not produce the same neuroprotective effects that occur via stem cell transplantation and cannot prevent secondary cell death . Given tExamination of the electron transport chain (ETC), specifically complexes I–IV, can be performed using ETC complex inhibitors to study each portion of the chain in isolation. Mouse models with mutated mitochondria are instrumental in this investigation in order to definitively determine whether it is the mitochondria themselves that confer the neuroprotection or whether a different characteristic of the stem cell is responsible . When diThe safety of BM-MSCs compared to other sources of stem cells is relatively well established . NeverthUp to this point, we concentrated on literature that characterizes the transfer of mitochondria from stem cells to endothelial cells and neurons in the context of the ischemic brain. However, stroke patients often suffer maladies that extend beyond the brain, and complete functional improvement must address these aspects of recovery as well. A prime example of this is that ischemic stroke may cause damage to the eye, leading to visual impairment and a significant delay in recovery ,37. ImpoIt is valuable to understand the role of mitochondrial dysfunction in cerebral and ocular disease post-stroke due to the markedly similar pathology and treatment options between these two conditions . In addiThere are considerable benefits to using MSC therapy to treat ischemia-induced eye damage, such as enhanced preservation of retinal ganglion cells. The decreased cell death is likely due to improved mitochondrial function, which may be due to MSC-derived mitochondrial transfer to the retinal ganglion cells . MSC traThe interaction of creatine and phosphocreatine conversion prevents lapses in cellular energy supplies under healthy conditions. However, it is still possible for the energy supply to be damaged under ischemic conditions, worsening mitochondrial dysfunction. Creatine supplementation possesses therapeutic characteristics in various neurodegenerative disorders that may address the lack of energy supply and the normal function of the mitochondria . TherefoBased on previously mentioned studies, transferring healthy mitochondria by exogenous MSCs can potentially restore respiratory functions in ischemic retinal cells, reducing cell loss. Future studies should investigate how MSCs successfully transfer healthy mitochondria to retinal ganglion cells. Studies should also observe and describe the metabolic and proteomic properties of MSC-derived mitochondria post-transplantation into ischemic retinal cells. EPCs’ affinity for BBB repair makes them a favorable MSC subtype. EPCs are known for being safe and effective to use in stem cell therapy. Additionally, their ability to donate healthy mitochondria justifies the need to further investigate its effects on retinal ischemia. However, the study presents a significant limitation. Specifically, no known study provides a detailed report regarding the physical characteristics of MSC that are involved in the mitochondrial transfer in retinal ischemia . The funStroke-induced ischemia results in insufficient oxygen delivery to cells and prevents mitochondria from performing cellular respiration. The ensuing loss of ATP is not compatible with cellular viability and ultimately precipitates mitochondrial dysfunction and cell death. In response to stroke and stroke-like lesions, cells upregulate mitochondrial synthesis to compensate for damaged mitochondria . A varieDespite the innovations in stroke therapy over the past decade, novel methods of research continue to elucidate fundamental information on the mechanistic role of mitochondria in stroke and enable the development of powerful new therapeutic strategies. A novel technology, Seahorse XFe24, measures mitochondrial respiration and allows investigators to directly detect changes in cellular energetics, rather than relying on cellular signaling . This teSeveral pharmaceutical agents, such as the dopamine D2 receptor antagonist pramipexole (PPX), facilitate neuroprotection through the action of mitochondria. Administration of PPX to transient MCAO model rats after an ischemic stroke reduces infarct volume, neurological deficit severity, mitochondrial ROS formation, mitochondrial calcium concentration, and swelling of the mitochondrial membrane, while simultaneously increasing oxygen consumption and the respiratory control ratio . TherefoThe pharmacological administration of tetrahydrocurcumin (THC) also alleviates mitochondrial dysfunction and improves functional capacity and motor coordination. THC epigenetically reduces plasma and tissue homocysteine (Hcy) levels and Hcy-induced mitochondrial oxidative stress . THC treAnother drug-based approach to mitochondrial dysfunction is the use of nicotinamide mononucleotide (NMN) to increase NAD+ levels. NMN extends the lifespan of mice with the mitochondrial disease Leigh Syndrome by normalizing NAD+ redox imbalance and lowering H1F1a accumulation in skeletal muscle . FurtherCationic arginine-rich peptides (CARPs) are another candidate pharmacological therapeutic that specifically enhance mitochondria-mediated neuroprotection in stroke. CARPs are small peptides, composed of up to 30 amino acids, that cross the BBB and localize to mitochondria in neurons. This property alone highlights their value as a pharmacologic treatment for stroke, as many other promising drugs do not effectively cross the BBB, making their administration difficult or ineffective. Once in the mitochondria, CARPs efficiently eliminate ROS that accumulate during ischemia and restore proper function of the mitochondria, rescuing the cell from free radical damage and reestablishing cellular viability .Although restoring the respiratory functions of mitochondria improves stroke outcomes, this is not the only strategy for recovery. Autophagy, the process of degrading and recycling damaged or unnecessary cellular components, can also mitigate mitochondrial dysfunction. A high salt diet is particularly dangerous because it increases the risk of hypertension-related stroke occurrence, reduces the efficiency of autophagy, and downregulates the production of the electron transport chain enzyme NDUFC2 . HoweverThe proteins ULK1, NDP52, and TANK-Binding Kinase 1 (TBK1) are also meaningful targets for stroke therapies through targeting autophagy. TANK1 recruits the ULK1 complex to the NDP52 receptor to initiate autophagy under conditions of starvation . TherefoAnother potential target of autophagy-based treatments involves the small molecule Compound R6 and its regulation of mitochondria-mediated apoptosis. The release of cytochrome c from damaged mitochondria activates the intrinsic apoptotic caspase-9/3 cascade and results in cell death . CompounAlong with autophagy, manipulating the discrete molecular mechanisms of mitochondria to enhance mitophagy is another approach to ameliorate stroke-induced mitochondrial dysfunction. Cell cycle progression in the presence of impaired mitochondria generates damaged daughter cells, further exacerbating tissue injury and delaying recovery. However, the serine/threonine kinase PINK1 and the E3 ubiquitin ligase Parkin mediate the elimination of these impaired mitochondria through induction of TBK1 to upregulate mitophagy, the targeted recycling of mitochondria. By directing TBK1 to the mitochondrial membrane, away from its role at the centromere during mitosis, PINK1 and Parkin halt the cell cycle at the G2/M phase . TherefoIn addition to enhancing TBK1-mediated mitophagy, PINK1 upregulates the Parkin-induced mitophagy pathway in the presence of damaged mitochondria. During an ischemic injury, the depleted mitochondrial membrane potential inhibits PINK1 importation to the inner mitochondrial membrane (IMM). Instead, PINK1 binds to Tom 7, accumulates on the outer mitochondrial membrane (OMM), then activates Parkin-induced mitophagy. However, the IMM-resident protease OMA1 cleaves PINK1 in the absence of Tom 7, abolishing mitophagy . Hence, While the PINK1/Parkin pathway is valuable to preserve non-neuronal cells, Parkin-induced mitophagy is not as effective in neurons as only a small fraction of mitochondria in axons undergo mitophagy . HoweverMultiple cellular pathways spur mitochondrial deterioration in ischemic stroke. Apoptosis in mitochondria is upregulated during ischemic stroke and is associated with continuous mitochondrial permeability transition pore (MPTP) opening in the inner and outer mitochondrial membranes . ROS proMitochondrial transporters are also important in preventing atherosclerosis, the accumulation of fatty plaques on the inner wall of arteries, which is a significant risk factor for stroke. Poor metabolism or excess intake of lipids intensifies atherosclerotic plaque buildup and heightens the chance of stroke and ischemic brain injury. The mitochondrial calcium uniporter (MCU) prevents lipid accumulation and maintains appropriate bioenergetics by facilitating oxidative phosphorylation in the mitochondria . HoweverAnother source of mitochondrial dysfunction that may exacerbate stroke pathology is the mitochondrial ADP/ATP carrier. Mitochondrial ADP/ATP carriers are located in the impermeable mitochondrial membrane and transport ADP into the mitochondrial matrix and ATP out for use as energy . InapproAstrocytes transfer their healthy mitochondria to neurons in the peri-infarct area post-stroke, and this endogenous neuroprotective mechanism is a candidate for stroke-therapy. In particular, the nuclear and desmosome-associated protein Pinin (Pnn) upregulates anti-apoptotic Bcl-2 expression, promotes ERK signaling, reduces pro-apoptotic cleaved caspase-3 production, and enhances astrocyte survival. Therefore, therapeutically augmenting Pnn expression may improve the endogenous capacity of astrocytes to protect neurons and repair ischemic tissue in the brain .Hyperbaric oxygen therapy (HBOT), which delivers pure oxygen to patients in special high-pressure rooms, modulates inflammation in traumatic brain injury (TBI) when given after the onset of tissue damage. However, pretreatment with HBOT also reduces cell death and improves post-stroke outcomes by inducing endogenous astrocyte-based mitochondrial transfer to neuronal cells. The prophylactic use of HBOT to enhance neuroprotection circumvents the need for invasive surgical treatment and potentially toxic drug-based approaches . AdditioMitochondrial repair for stroke highlights the integral role of mitochondrial function on cell survival and neurological improvement. Mitochondrial dysfunction closely accompanies post-stroke secondary cell death. The hypoxic environment reduces energy production, further exacerbating stroke symptoms. Identifying a reliable method of mitochondrial transfer represents the first step towards developing an effective stroke treatment and is crucial to restoring cell function . To thisWhile the benefits of stem cell therapy are clear, the mechanism is not. Determining the precise location of transfer between the donor and recipient cells will provide crucial insights into the mechanism and therapeutic actions of mitochondria. Such knowledge will guide efforts to optimize transfer conditions and maximize the beneficial effects of stem cells . To thisAlthough mitochondrial transfer is theoretically bidirectional, molecular signals released by damaged cells preferentially direct the movement of mitochondria and mtDNA from MSCs to damaged neurons . One sucDeleting mitochondria from stem cells abolishes the regenerative benefits they confer to damaged endothelial cells, supporting the hypothesis that these organelles are responsible for repair. Furthermore, transferring mitochondria directly into ischemic brain tissue restores cellular energetics, facilitates homeostasis of the central nervous system (CNS), and resolves the inflammation that causes secondary cell death . Stem ceMSCs are the most common stem cell source for mitochondrial transfer and provide a protective mechanism to save damaged cells from mitochondrial dysfunction in response to stress. The transfer of MSC-derived mitochondria to endothelial cells can repress apoptosis after an IR injury by restoring aerobic respiration. The results of studies investigating this transfer are encouraging, paving the way for stem cell transplantation therapy for ischemic stroke . An in vMSCs achieved efficacy of mitochondrial transplantation via intravenous transplantation into a middle cerebral artery occlusion (MCAO) mouse model. Here, retinal ischemia caused ganglion cells to deteriorate, impairing mitochondrial activity. These findings suggest that MSCs ameliorate mitochondrial dysfunction and ganglion cell death, as was observed 14 days after the stroke . In vitrThe effect of OGD on MSCs derived from the perivascular region, cord lining, and Wharton’s jelly of the human umbilical cord also implicated a key role of mitochondria in these specific MSC tissue sources. The mitochondria in the perivascular region MSCs showed the greatest activity while the MSCs from the cord lining demonstrated the highest survival rate. These findings suggest that hUC-MSCs may be a good source for mitochondrial transplantation for ischemic stroke treatment . AdditioHuman induced pluripotent stem cells (iPSCs) are also the subject of recent studies of mitochondrial transfer. PD model astrocytes derived from human iPSCs spontaneously release healthy mitochondria in damaged neuron cultures. This iPSC-induced mitochondrial transfer significantly ameliorates dopaminergic neuron damage and imparts neuroprotective effects . iPSC’s Spinal cord injury (SCI) models of mitochondrial transfer via bone marrow mesenchymal stem cells (BMSC) show promising results as well. Symptoms of both diseases are very similar: hypoxia, mitochondrial degeneration, oxidative stress, vascular injury, and axonal degeneration . HealthyThe omnipresent phenomenon of mitochondrial transfer allows for many applications in combination with stem cells. Contemporary literature details the efficacy of mitochondrial transfer in improving stroke, cardiovascular injury, spinal cord injury, and Parkinson’s disease outcomes. The regenerative capacity demonstrated in a variety of tissues warrants its consideration as a primary therapeutic option. In particular, the physiological and pathological improvements seen in treating ischemic stroke illustrate the capability of mitochondrial transfer therapy. However, before moving into clinical trials, the optimal stem cell type must be identified to maximize the efficacy and potency of treatment. Further investigation is needed to discover the true potential of stem cell-based mitochondrial transfer therapy and improve long-term stroke outcomes.


Research has shown the amount of effort we expend towards our goals depends on a sense of self-efficacy, perception of task difficulty, and likelihood of achieving our goal. All of these processes are susceptible to the influence of affect. For example, negative moods may impede goal achievement by increasing perceptions of difficulty . Negative experiences (such as past failures) can encourage these negative moods and subsequently impact self-efficacy . Findings from self-efficacy research  suggest that older adults may be particularly susceptible to the impacts of negative affect on effort mobilization, especially when tasks already seem challenging, with little chance of success. Perception of task difficulty, then, impacts the amount of effort exerted in completing the task. The present study sought to examine the factors that impact perceptions of difficulty and subsequent effort expenditure, represented by systolic blood pressure responsivity (SBP-R). Younger (N = 41) and Older (N = 163) adults completed a difficult cognitive task as part of a larger, longitudinal study, as well as measures of trait affect before study sessions. Our findings indicate younger adults exert less effort overall than older adults; however, when negative trait affect is considered, we find that higher levels of negative affect in older adults reduced task engagement. These results provide support for an effect of negative affect on task appraisals and posited age-related differences in effort mobilization.


Brain pathologies are increasingly understood to confer mobility risk, but the malleability of functional brain networks may be a mechanism for mobility reserve. In particular, white matter hyperintensities (WMH) are strongly associated with mobility and alter functional network connectivity. To assess the potential role of brain networks as a mechanism of mobility reserve, 116 participants with MRI from the Brain Networks and Mobility Function (B-NET) were categorized into 4 groups based on median splits of SPPB scores and WMH burden: Expected Healthy , Expected Impaired , Unexpected Impaired  and Unexpected Unhealthy . Functional brain networks were calculated using graph theory methods and white matter hyperintensities were quantified with the Lesion Segmentation Toolbox (LST) in SPM12. Somatomotor cortex community structure (SMC-CS) was similar between UH and EH with both having higher consistency than EI and UI. However, UH displayed a unique increase in second-order connections between the motor cortex and the anterior cingulate. It is possible that this increase in connections is a signal of higher reserve or resilience in UH participants and may indicate a mechanism of compensation in regards to mobility function and advanced WMH burden. These data suggest functional brain networks may be a mechanism for mobility resilience in older adults at mobility risk due to WMH burden.


The recurrence of symptoms present before cholecystectomy may be caused by a cystic duct remnant. The resolution of cystic duct remnant syndrome may require surgical resection, but identification of the duct remnant during laparoscopic surgery may be difficult because of adhesions following the previous procedure. Open surgery, which is more invasive than laparoscopic surgery, is frequently chosen to avoid bile duct injury.The patient was a 24-year-old woman with previous laparoscopic cholecystectomy for chronic cholecystitis and repeated attacks of biliary colic. The postoperative course was uneventful, but computed tomography revealed a remnant cystic duct calculus. Ten months after surgery, the patient returned to our department for right hypochondriac pain. Laparoscopic remnant cystic duct resection was performed with intraoperative near-infrared (NIR) fluorescence cholangiography to visualize the common bile duct and remnant cystic duct. The postoperative course was uneventful and the patient was discharged on day 3 after surgery. At the 6-month follow-up, she had no recurrence of pain.Laparoscopic surgery with NIR cholangiography is a safe and effective alternative for the removal of a cystic duct remnant calculus after cholecystectomy. Post-cholecystectomy syndrome (PCS) is a recurrence of upper abdominal and right hypochondriac pain, jaundice, dyspepsia, gastrointestinal disorders, and vomiting experienced before cholecystectomy . PCS mayA 24-year-old woman with chronic cholecystitis and episodes of biliary colic underwent laparoscopic cholecystectomy at our hospital. Although preoperative computed tomography (CT) revealed a cystic duct calculus, the complete removal of the calculus could not be confirmed considering bile duct injury because there were moderate chronic inflammations around the cystic duct. The postoperative course was uneventful and without pain. Ten months later, the patient visited the outpatient clinic because of hypochondriac pain. Laboratory results showed normal liver function, and inflammation and jaundice were absent. CT revealed a cystic duct remnant calculus at the same site as before Fig. . MagnetiPCS is characterized by the recurrence of symptoms experienced before cholecystectomy . In CDRSPrevious systematic reviews have described the potential advantages of fluorescence cholangiography over conventional cholangiography during laparoscopic cholecystectomy . In addiThis patient was safely and successfully treated for a cystic duct remnant calculus by relatively noninvasive laparoscopic surgery in combination with NIR fluorescence cholangiography and ICG.


Viruses on “Plant Virus Pathogenesis and Disease Control” give new, important information addressing different aspects of this topic.Plant viruses are emerging and re-emerging to cause important diseases in many plants that humans grow for food and/or fiber, and sustainable, effective strategies for controlling many plant virus diseases remain unavailable. However, cutting-edge technological approaches in cell and molecular biology and rapidly accumulating virus sequence datasets are allowing us to gain new insights into mechanisms involved in pathogenesis and how interactions between plants and viruses affect disease development. In some cases, these offer opportunities for novel approaches to target plant viruses and help control the diseases they cause. Seven original articles in this Special Issue of Solanum lycopersicum) in several parts of the world. Klap and colleagues show further complexity associated with TBRFV-induced disease. They show that when TBRFV co-infects plants with the potexvirus, pepino mosaic virus (PepMV), more severe symptoms develop [Tomato brown rugose fruit virus (TBRFV) is a recently described and rapidly spreading tobamovirus affecting tomatoes ( develop . PepMV cGlycine max) are a globally important crop plant and soybean mosaic virus (SMV) occurs wherever soybeans are grown, in part due to its seed transmissibility. Bao and colleagues developed a GFP-recombinant SMV system to assess SMV-soybean interactions [Soybeans  technology to assess the role of microRNA nbe-miR1919c-5p in infections of N. benthamiana plants by tobacco curly shoot virus (TbCSV) and its betasatellite (TbCSB) DNA [Three groups addressed the roles of non-coding RNAs in plant virus infections ,6,7. LiuThese papers are representative of the approaches and opportunities that are available now to gain a better fundamental understanding of plant virus-induced pathogenesis. Obtaining a more fundamental understanding of plant-virus interactions is necessary if we are going to develop efficacious, environmentally sound approaches to control plant diseases caused by plant viruses. We now have fantastic new tools including NGS and bioinformatics approaches to look at virus diversity and host responses to virus infection at the transcriptome but also small and large non-coding RNA levels, not only in different plant genotypes but also in different plant tissues. However, the diversity of papers here also shows that we cannot ignore virus-host biology, and we must consider biology to help us accurately interpret and use what we are finding with modern technologies.


Although the physical and cognitive benefits of moderate-vigorous intensity physical activity (MVPA) for older adults is well documented, this population often faces age-related functional and physical limitations impeding recommended MVPA participation. Recently, there has been a surge of interest in the independent health benefits of light-intensity physical activity (LPA) and its association with morbidity and mortality risk. LPA is the most common form of activity among older adults and its potential to combat cognitive aging needs to be investigated. The purpose of this scoping review was to catalog existing evidence on the association between device-based or technologically measured LPA and cognition among healthy older adults, identify trends in the literature, and pinpoint future areas of research. Six electronic databases were searched between January and August 2020. Eighteen published studies met the inclusion criteria: one acute exercise study, two randomized control trials (RCTs), twelve cross-sectional studies, and three longitudinal studies. Overall, n=9 studies  reported a significant, positive relationship between LPA and one or more cognitive outcomes including memory, attention, executive function and global cognition (MMSE/MOCA). These heterogeneous findings can largely be attributed to the diverse study designs, inconsistent definitions of LPA and numerous assessments used to test the cognitive domains. Collectively, these findings suggest LPA may be a potential lifestyle intervention to improve cognition among healthy older adults. However, the inconsistent approaches used among these studies suggests a more concerted, unified scientific approach and rigorous methodology are needed to further understand the LPA-cognition relationship.


Social engagement may confer cognitive benefits in older adulthood, but studies have typically been restricted to largely non-Hispanic White (NHW) samples. Levels of social engagement vary across race such that NHW report larger social networks, more frequent participation in social activities, and greater social support than non-Hispanic Blacks (NHB). Associations between social engagement and cognition may also vary by race, but research is sparse. The current cross-sectional study examined associations between different aspects of social engagement and episodic memory performance, as well as interactions between social engagement and race among NHB and NHW participants in the Michigan Cognitive Aging Project . Social engagement  was self-reported. Episodic memory was a z-score composite of immediate, delayed, and recognition trials of a list-learning task. Separate hierarchical linear regression models quantified interactions between race and each of the three social engagement variables on episodic memory, controlling for sociodemographics, depressive symptoms, and health conditions. Results showed a main effect of more frequent social activity on better episodic memory, as well as an interaction between race and social support indicating a significant positive association in NHB but not NHW. These preliminary findings suggest that participating in social activities may be equally beneficial for episodic memory across NHB and NHW older adults and that social support may be particularly beneficial for NHB. Future research is needed to determine the potential applications of these results in reducing cognitive inequalities through the development of culturally-relevant interventions.


Choir interventions confer psychological benefits for persons with dementia (PwD) and their caregivers. However, less is known about whether physiological function also exhibits improvements pursuant to such social-cognitive interventions. The present study, based upon a subsample of the Voices in Motion (ViM) project, explored whether participation in an intergenerational choir results in systematic improvements in gait velocity  for both informal caregivers  and PwD . Longitudinal burst data from the first of three cohorts spanning 4 assessments over 3.5 months was analysed using multilevel modeling. Whereas caregivers exhibited significant improvements (p<.05) in gait velocity, PwD showed no improvement. Ongoing analyses are exploring additional cohorts, and whether improvements in gait dynamically covary with reductions in comorbidities . These results underscore the potential of choir for facilitating both psychosocial and physiological function for caregivers and PwD.


An integrated approach for assessing ventricular pump function, diastolic compliance (EDPVR), myocontractility and pulmonary vascular resistance would be of clinical interest. In addition to pump function, MRI guided catheterization was demonstrated to accurately measure myocontractility and vascular resistance. We now extended this method for acquisition of the EDPVR. Subsequently, this approach was applied in patients with Fontan hemodynamic in which abnormalities in pulmonary vascular, myocontractile and diastolic properties are debated.The EDPVR was determined by synchronizing invasive ventricular pressures with cine and real-time MRI derived ventricular volumes and pulmonary/aortic blood flow measurements.In 7 pigs the MRI and conductance-catheter method (gold standard) were compared for measuring the EDPVR at rest and during dobutamine.Parameters of global function, myocontractility (ESPVR), vascular resistance and EDPVR were measured with MRI at rest and under dobutamine in 14 patients with Fontan circulation.Bland-Altman test showed agreement between the conductance-catheter and MRI method. In the pigs, there was in both ventricles during dobutamine a right/bottom shift of the EDPVR, the stiffness co efficient decreased slightly (p < 0.051). In the patients during dobutamine we noted failure to increase stroke volumes despite increased contractility and evidenced diastolic dysfunction. Active relaxation was inconspicuous but the EDPVR shifted towards the left/top, the stiffness constant remained unchanged. Pulmonary resistance decreased slightly (p = 0.058) and thus showed adequate response to augmented cardiac outputs.This novel MRI method provides differential information about diastolic, systolic and vascular function. The method evidenced that in Fontan patients diastolic dysfunction is an important pathophysiologic cause of heart failure.


Chronic stress creates vulnerability to adverse mental and physical health outcomes in later life. While claims about the negative effects of stress on health are primarily based on self-report, it is unclear how subjective stress measures (chronic or perceived stress) and other environmental or individual characteristics  relate to physiological stress response. This study examines which contextual features contribute to differences in physiological stress reactivity among adults at risk of type II diabetes . Psycho-social stress was induced via Trier Social Stress Test. Using advanced selection methods, we simultaneously explore multiple predictors and illustrate how different sets of risk and protective factors contribute to normal or abnormal stress reactivity profiles. Preliminary results suggest that the top five important predictors are education, contact with friends, perceived stress, ruminative coping, and sedentary behavior. Implications for research and targeted interventions are discussed.


Our purpose was to document the swept source optical coherence tomography (SSOCT) findings in a patient with Shaken baby syndrome (SBS).SSOCT was obtained without sedation in a six-month-old girl with bilateral multilayered retinal hemorrhages due to SBS. It documented vitreoretinal interface abnormalities, including internal limiting membrane (ILM) detachment with retinal traction, in association with other specific changes in the inner and outer retinal layers. Six weeks later, retinal hemorrhages had substantially resolved, and there was optic disc pallor. OCT showed ILM reattachment with release of retinal traction and the development of severe diffuse retinal atrophy involving the fovea.SS OCT can provide useful information in SBS, revealing a wide variety of vitreoretinal interface, inner, and outer retinal changes not detected by clinical examination. It also may have a prognostic value over follow-up. Shaken baby syndrome (SBS), also known as abusive head trauma, refers to a constellation of clinical findings including bilateral retinal hemorrhages, subdural hemorrhage, and anoxic encephalopathy . RetinalA previously healthy six-month-old girl was brought to the emergency department for paroxysmal crying with brief episodes of loss of consciousness. On physical examination there was a bulging fontanel with associated weak axial posture. A cerebral computed tomography (CT)-scan demonstrated extensive bilateral subdural hemorrhages. The child was admitted to the Pediatric Intensive Care Unit. Ophthalmological examination revealed a poor pupillary response to bright light in both eyes. There were no external signs related to ocular trauma. Fundus examination by indirect ophthalmoscopy revealed bilateral preretinal and intraretinal hemorrhages involving the posterior pole and midperiphery. There was a bilateral boat-shaped premacular hemorrhage. This hemorrhage was larger and associated with a prominent surrounding ring-shaped white retinal fold in the right eye Fig. . A diagnThree days after hospitalization, the patient underwent swept source OCT imaging with the DRI OCT Triton plus . Multiple SS-OCT scans could be obtained without sedation, the infant being held and her eyelids kept open by an assistant. OCT confirmed multilayered retinal hemorrhages in both eyes. It showed a dome-shaped detachment of the internal limiting membrane (ILM) overlying the macular hematoma bilaterally, with associated perifoveal retinal traction corresponding to the retinal fold seen clinically in the right eye Fig. . Other SSequential follow-up examinations showed gradual resolution of the neurological symptoms and improvement of pupillary response to light. Six weeks after initial examination, retinal and preretinal hemorrhages had substantially resolved, and there were bilateral areas of subretinal fibrosis and optic disc pallor, mainly in the right eye Fig. .Fig. 2aSS OCT, six weeks after initial presentation, showed complete reattachment of the detached ILM, with release of retinal traction and resolution of other acute findings. There was a bilateral marked diffuse retinal atrophy involving the fovea with associated subretinal hyperreflective lesions corresponding to the areas of subretinal fibrosis seen clinically Fig. .To the best of our knowledge, this report is the first to describe the use of SS OCT in the assessment and monitoring of retinal disease associated with SBS. Thanks to the faster acquisition times of SSOCT technology, OCT scans could be obtained without sedation, although an assistant was required to hold the infant’s head. Until recently, time domain and conventional or hand-held spectral domain (SD)-OCT have been rarely used in very young children with acute SBS –5. OCT iAnother dimension of ocular changes in SBS was described in the field of forensic pathology. OCT findings may provide valuable information suggestive of child abuse in the absence of external evidence of trauma .Our study expands the OCT spectrum of SBS to include a wide variety of previously undescribed vitreous and retinal changes, including alterations of the outer retinal layers. On follow-up OCT examination, severe retinal atrophic changes became evident after resolution of hemorrhages and other acute findings. Our data show that macular atrophy may be an important causative mechanism of severe vision loss in children with SBS.In conclusion, thanks to its faster acquisition time and deeper penetration, SSOCT may be useful in the evaluation and monitoring of ocular disease in awake young children with SBS. It can provide useful information, revealing a wide variety of vitreoretinal interface, inner, and outer retinal changes not detected by clinical examination. It also may have a prognostic value over follow-up.


The geometric framework for nutrition has largely been applied to macronutrients in experimental settings. Here, we utilize the framework to examine both macro and micronutrient intake patterns in observational human data. We used nutritional intake patterns  of 1754 older Quebecers from the NuAge cohort to predict multi-system homeostatic dysregulation scores calculated from 30 biomarkers. Intermediate intake of both macro- and micronutrients was generally associated with lower dysregulation scores . Furthermore, there were often nutrient-nutrient interactions, such that the optimal level of one nutrient depends on the intake level of others. However, higher protein intake was generally associated with better health, and results varied substantially across different dysregulation systems. Accordingly, even though nutrition does have important effects on health trajectories during aging, it will be challenging to arrive at population-level recommendations to fine-tune nutrient intake patterns to optimize health beyond “everything in moderation.” Part of a symposium sponsored by the Nutrition Interest Group.


The current study takes a dyadic perspective to understand how self-perceptions of aging are associated with C-reactive protein, an inflammation marker, among older adult married couples. The potential moderating role of marital support and strain are also examined. Respondents include 668 married couples who participated in the 2014 wave of the Health and Retirement Study. Actor-Partner Interdependence Models were conducted in Mplus. Age, functional limitations, income, and race served as covariates. Husbands’ greater positive perceptions of aging were significantly associated with their own lower levels of inflammation. Husbands’ greater positive perceptions of aging were significantly associated with lower levels of inflammation for women who reported lower levels of marital strain; this was not the case for women who reported higher levels of marital negativity. This study exemplifies how relationship factors are necessary to consider when examining age perceptions and health among marrieds.


The knowledge regarding hypothalamic integration of metabolic and endocrine signaling resulting in regulation of food intake is scarce in fish. Available studies pointed to a network in which the activation of the nutrient-sensing  systems would result in AMP-activated protein kinase (AMPK) inhibition and activation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Changes in these signaling pathways would control phosphorylation of transcription factors cAMP response-element binding protein (CREB), forkhead box01 (FoxO1), and brain homeobox transcription factor (BSX) leading to food intake inhibition through changes in the expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opio melanocortin (POMC), and cocaine and amphetamine-related transcript (CART). The present mini-review summarizes information on the topic and identifies gaps for future research. Two neuronal populations in the mammalian hypothalamic arcuate nucleus respond to a rise in the levels of circulating metabolites  . They renucleus lateralis tuberis (NLTv), an analog of arcuate nucleus , specific fatty acid receptors (FFAR), fatty acid translocase, and lipoprotein lipase. Evidence is also available in other species like grass carp  induced a rise in hypothalamic Bsx mRNA abundance (In fish, evidence regarding BSX role in hypothalamus is limited  with a f nucleus  as well  nucleus  in paralbundance .Npy and Agrp leading to a decrease in food intake (Npy and Agrp (cAMP response-element binding protein is another transcription factor hypothesized to be involved in the connection between brain metabolism and neuropeptides expression. Accordingly, in mammals, a decrease in CREB levels induced a decrease in mRNA abundance of d intake . CREB prand Agrp  while leand Agrp  or food and Agrp .In fish, available information regarding CREB involvement in food intake regulation is restricted to rainbow trout. In this species, CREB phosphorylation status decreased in response to raised levels of oleate , octanoaAgrp mRNA values while those of Pomc decreased, changes favoring a decrease in food intake (Forkhead box01 is likely involved in the relationship between metabolic changes in hypothalamus and the production of neuropeptides . Thus, id intake .Foxo1 to changes in nutrient levels. However, changes observed in fish would be comparable with those observed in mammalian hypothalamus under anorectic conditions like feeding a high-fat diet (In fish, FoxO1 was characterized in brain in rainbow trout  and turbfat diet  or treatfat diet . Akt actfat diet , which afat diet . In fishfat diet , octanoafat diet , or insufat diet  but not fat diet . These rAgRP/NPY and CART/POMC neurons involved in the integration of signals from nutrient sensors also have receptors for hormones like leptin, ghrelin, insulin, CCK, or GLP-1, among others . The binbsx and mtor mRNA abundance as well as in the presence of oleate for Akt phosphorylation status, and foxo1 and creb1 mRNA abundance. No other studies characterized in fish putative interactions in hypothalamus. However, in rainbow trout treatment with different hormones alter nutrient sensing mechanisms in hypothalamus (In fish, only two studies carried out in rainbow trout demonstrated interactive effects in hypothalamus between nutrient-sensing mechanisms and hormones such as ghrelin and insulin. The presence of oleate counteracted ghrelin effects on AMPK . In the thalamus  as demonThe knowledge available in fish about hypothalamic integration of information of metabolic and endocrine nature eliciting changes in expression of neuropeptides ultimately regulating food intake is limited . StudiesThe author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.