The cornea is a transparent avascular structure located in the front of the eye that refracts light entering the eyes and also serves as a barrier between the outside world and the internal contents of the eye. Like every other body part, the cornea may suffer insult from trauma, infection, and inflammation. In the case of trauma, a prior infection that left a scar, or conditions such as keratoconus that warrant the removal of all or part of the cornea (keratoplasty), it is important to use healthy donor corneal tissues and cells that can replace the damaged cornea. The types of cornea transplant techniques employed currently include: penetrating keratoplasty, endothelial keratoplasty (EK), and artificial cornea transplant. Postoperative failure acutely or after years can result after a cornea transplant and may require a repeat transplant. This minireview briefly examines the various types of corneal transplant methodologies, indications, contraindications, presurgical protocols, sources of cornea transplant material, wound healing after surgery complications, co-morbidities, and the effect of COVID-19 in corneal transplant surgery. The cornea is an avascular tissue that is transparent due to the arrangement of its component cells, its avascularity and the metabolic processes its endothelium carries out . It measWe searched the Pubmed database using the following search criteria; “corneal transplantation” [MeSH Terms] OR  OR “corneal transplantation” [All Fields] OR (“cornea” [All Fields] AND “transplantation” [All Fields]) OR “cornea transplantation” [All Fields]. Given that this study was focused on CT in the last decade, we narrowed the search criteria to 2012 to 2023, resulting in a return of 3021 results. The search words using only “transplant” or “keratoplasty” or other single words were not considered in our minireview to avoid an overabundance of potentially impertinent studies. This search strategy was limiting and could have potentially and unintentionally excluded opinion leaders in this field of research. A Prisma Table was also generated, showing further stratification steps.Corneal transplantation (CT) is indicated via any processes leading to loss of corneal transparency, with neuroretinal integrity and optimal visual potential otherwise preserved . CT is uCTs are among the most common procedure performed in many tertiary eye centers worldwide ,10,11,12Proper patient selection is key to yielding reasonable CT outcomes. A thorough corneal, anterior and gross posterior segment evaluation, in addition to a systemic workup, should ideally be carried out prior to qualifying all potential CT candidates. With regard to preoperative corneal evaluation, the depth of corneal tissue scarring and evidence of corneal ectasia should be determined. Detection of keratic precipitates  indicates active or latent migration and deposition of immune moieties. The resultant hyperimmune sensitization disrupts the ocular immune privilege, decreasing the chances of post-graft tissue survival by more than four-fold . EstabliWhen significant corneal stromal haze or widespread leucomatous scarring impairs intraocular evaluation, imaging modalities such as anterior segment-ocular coherence tomography (AS-OCT), ultrasound biomicroscopy (UBM), and B scan ultrasonography can be respectively utilized to gain a gross outline of individualized intraocular integrity. Corneal central thickness (CCT) measurements with pachymetry have, in the past, been correlated with corneal endothelial cell (CEC) loss , mostly Under normal circumstances, the trilaminar cornea is devoid of lymphocytes. The cornea’s innate defense systems are provided by bacteriostatic enzymes in the tear film, the equilibrium of microbiome/normal flora on the ocular surface and the corneal epithelial barrier attributes . This inStandardized procedures of donor corneal tissue viability analysis are usually followed prior to harvesting and cryopreservation with corneal banks . With reRooij et al. conducted a comparative analysis of three standard methods of CT for the management of Fuchs endothelial dystrophy. They found that there was no significant difference between improvement using conventional PK, inverted mushroom PK and DSAEK .Globally, the need for donor corneal tissue to ease the burden of avoidable corneal blindness far outweighs the availability of viable graft tissue for CT . The demSafe strategies for extending the viability period of donor tissue before allografting have been explored . GlyceroAutologous graft sourcing also represents a viable strategy in rare cases where healthy corneal tissue on the contralateral side may not be of great functionality due to late comorbid ocular disease . HomonymCorneal transplantation of autologous tragal perichondrium with an amniotic membrane overlay has been reported to yield symptomatic relief among patients with bullous keratopathy compared to controls . CulturiA common complication of wound healing is neovascularization. Topical bevacizumab application post-CT four times daily for 24 weeks was found to statistically reduce the occurrence of neovascularization . Better Immune rejection after CT has been successfully managed via donor-derived, tolerogenic dendritic cells . A blockIn cases where there is a severe corneal ulceration threatening the integrity of the globe, a penetrating keratoplasty can be the last chance of saving that eye . The keyCorneal donation involves identifying a potential donor eye, preparing the eye for removal of the graft, extraction of donor tissue and storage. Therefore, the preparation of corneal grafts takes up a critical stage in this regard due to the high demand for cornea tissue and relatively lower supply ,48. IntrHagenah and Winter reviewed recent trends in globe disinfection before graft extraction . They su2 in 14% of its participants and co-morbidities in corneal transplant medicine.The ECD can be a very important indicator of the eventual viability of the graft. Gupta and Gupta examined 100 eyes that received corneal transplants within a two-year period over periodic intervals. They reported that the most endothelial cell loss was seen in patients undergoing a repeat graft, while keratoconus-grafted eyes showed the lowest loss . AnotherThis relative scarcity of corneas for transplant puts their storage on the front burner for many researchers. The numbers of overall grafts properly stored and the eventual viability of the grafts when needed for eventual transplant are two key indices that can advise on the progress of corneal tissue storage development. Garcin et al. developed an active storage device which they called a bioreactor and compared its preservation abilities versus the organ culture storage technique. They published results showing that the bioreactor had a 23% higher rate of endothelial cell survival than the organ culture technique . They alFailure of the cornea graft (PGF).Immunological reaction by the host to the graft .Non-immunological factors such as spontaneous decompensation, glaucoma and diseases ,61. WounOther distinct factors .Generally, the causes of CT failure have been classified into:The cornea endothelium is an inner barrier to edematous damage from aqueous humor breaching into the cornea. Endothelial cell count (CEC) is therefore essential to assess the ability of the eye to retain this protective ability. Studies have shown that the CEC is significantly reduced when corneas are extracted for grafting . Jafarinp = 0.815).Cytokine elevation has also been observed in eyes that suffered CT failure , althougWound dehiscence is a common complication post-CT. A study was conducted in the Riyal Eye and Ear hospital to assess the incidence and clinical demographic of 72 eyes who visited a center for surgery . PeriopeCorneal opacities impede intraoperative visualization during cataract extraction and vitreoretinal surgery . PerformClinicians should also note that patients receiving immune checkpoint medication are at risk of CT rejection . Common Another study at a different center reported an incidence of microbial keratitis in 4.77% of 1508 eyes that had undergone CT . NatamycNon-infective unforeseen events can also complicate the CT process. Jarstad et al. reported a case of cardiac failure in an otherwise healthy young adult during CT surgery that was successfully managed . AnotherRare conditions like monoclonal gammopathy of undetermined significance are also implicated, especially in the presence of elevated levels of abnormal M proteins . Paniz-MAs with any grafting procedure, immunologic interactions between the host and donor tissue can be problematic. However, non-immunologic factors can also be a factor in the loss of CEC, even with patients receiving autologous CT . Repeat The avascularity and degree of sensory innervation of the cornea ensure the maintenance of its structural integrity and function. A deviation from the regular structural integrity and outline precipitated by cornea diseases is the fourth leading cause of blindness worldwide. Most visual impairments resulting from cornea morbidities are avertible and reversible. Cornea transplantation is a required surgical intervention in cornea diseases which results in a deep lamellar cornea structural deformity; however, as with most solid-organ transplants, the risk of transmission of infectious diseases to the handlers of donor tissues and recipients cannot be overlooked. The Eye Bank Association of America (EBAA) released updated recommendations and policy changes with the advent of the COVID-19 pandemic .The COVID-19 pandemic resulted in acute and chronic shortages of donor corneas in a healthcare system that already had a long list of patients waiting ,99. A stSeveral questions regarding the spread and transmission of SAR-CoV-2 in tears and ocular tissues have been asked. The first was to identify the presence of SAR-CoV-2 in tears which may enable its transmission and subsequent infection of ocular tissues . In a stThe shortage of donor tissue during the COVID-19 pandemic also had positive results. Clinicians reported an innovative procedure and were able to use a single donor cornea for four different recipients undergoing CT for different conditions . AnotherA 15-year review of corneal donations in southern Africa revealed that cultural beliefs have led to a marked reduction in donation numbers . HoweverGain et al. conducted a systematic review of reports on corneal transplant medicine and eye banks. They then conducted interview series among specialists spanning 148 different countries. In total, they reviewed 184,576 surgeries using 283,530 corneas obtained from 742 cornea banks. Their work concluded that there was indeed a scarcity of corneas worldwide. Their calculated availability was estimated at only one cornea for every 70 eligible transplant patients. They suggested an acceleration of alternative/artificial solutions such as keratoprostheses .The first CT took place in 1884 using a bovine cornea . CT has Amagai et al. reported the successful development of a novel tissue carrier for donor graft tissue . They vaTissue-engineered construct models for corneal endothelial keratoplasty have shown greater pharmacoeconomic potentials than those working with donor tissue . UltraviAzithromycin treatment regimen has been reported to reduce the incidence of high-risk allograft rejection in murine models . PreoperSteroid therapy after ocular surgery is indicated for the prevention of inflammation and also for its immunosuppressive properties. Poinard et al. conducted a study to assess the adherence of cornea transplant receivers to prescribed postoperative steroid therapy . SteroidTrone et al. also conducted a pilot study (Phase II) as part of a clinical trial to assess the safety of a new dropless PK which incorporated a subconjunctival steroid implant . FourteeAs already stated, conventional keratoplasty involves allogeneic transplantation of corneal tissue: tissue-specifics depending on the disease section of the cornea . NotablyKeratoprestheses require a clear central optic zone to enable refraction onto the retina. Historically, early KPro material consisted of convex glass sheets which served as optics surrounded by metallic rims made of silver, quartz, platinum and like materials . AttemptRetrospectively, the Boston type-1 KPro (with its phakic and aphakic models) and the Osteo-odonto KPro have reportedly recorded proven highest success rates. The use of the temporary Eckardt KPro and other retrievable soft contact lens media has been successfully trialed for posterior segment visualization during vitreoretinal procedures with combined keratoplasty ,143. EyePreoperative preparation requires ocular imaging and biometric analysis to determine anterior chamber depth; gross morphological iridocorneal angle integrity; crystalline lens presence/position; also, and retinal function and integrity (which may require electrophysiology in doubtful cases).Major complications reported post-KPro implantation include glaucoma, persistent autoimmune reaction with cases of coexisting system autoimmune disease -driven responses can help to avert further sight loss following KPro implantation.Corneal specialist surgeons should be globally incentivized to encourage uptake, training, and retraining in modern techniques of allograft transplantation. The major impediment to optimal management of corneal blindness aside from donor shortage remains post-CT rejection/graft failure. Finding solutions may depend on the rate of progress regarding the incorporation of either biological material or procedural modulation of stem cell differentiation to avascular corneal-like tissue, especially for immune-mediated graft failure. There will certainly be limitations to this approach, specifically in the exploitation of totipotent embryonic stem cells. Strategies to prolong the viability time of donor grafts would also serve to minimize cost effectiveness preoperatively. Demand for CT may also decrease if current advances in local ocular stem cell application and amniotic membrane transplantation reduce the incidence of corneal scarring following chemical injury and deep corneal ulceration.


There is a huge resource gap in mental health service provision & service utilisation in LAMIC including Pakistan. SOUL Programme has been established in the City of Larkana, on charitable donations, which utilises principles of home-based outreach and produces clinical and functional outcomes.SOUL programme focuses on collaborative working with patients & families. The objectives include recognition, treatment, family education & psychosocial support to maximize clinical, functional & occupational outcomes.Single cohort intervention  with innovative service structure and culturally relevant open label intervention design developed with local academic psychiatric unit in Larkano, Pakistan. Training was provided to local mental health professionals on diagnosis, delivering care & use of recognized clinical outcome measures.We have recruited a cohort of 160 patients on continual basis over time. Our analysis show a higher BPRS and lower GAF ratings for men in comparison to female cohort at the baseline. Our Ten year follow up has demonstrated statistically significant clinical / functional improvement on BPRS, CGI & GAF measures. The mean differences recorded for the individual measures after 12 months were BPRS, CGI-I and GAF and were all statistically significant. Innovative home-based community mental health intervention shows significant improvements in clinical and functional outcomes (with good effect size).SOUL Programme is a highly effective and cost-efficient intervention model for treatment of schizophrenia in a developing country setting. Our 10 year follow up study confirms the feasibility of this intervention model through close working with families of our patients.No significant relationships.


Yet, the relationship in humans between maternal overweight/obesity during pregnancy and fetal hypothalamic development remains largely unknown. Here, using an international  multi-site diffusion tensor imaging (DTI) dataset, we test the hypothesis that maternal pre-pregnancy BMI is associated with newborn offspring HTH mean diffusivity .An extensive body of animal literature supports the premise that maternal obesity during pregnancy can alter the development of the fetal hypothalamus  with implications for offspring obesity risk  using a high-resolution atlas-based definition of HTH. A total of n = 231 mother-child dyads were available for this analysis . The association between maternal pre-pregnancy BMI and newborn offspring HTH MD was examined separately in each cohort using linear regression adjusting for gestational age at birth, postnatal age at scan, sex, whole white matter mean diffusivity, and DTI quality control criteria. In post hoc analyses, additional potentially confounding factors including socioeconomic status, ethnicity, and obstetric risk were adjusted where appropriate.HTH MD was independently quantified in two separate BMI-matched cohorts  and remained significant after adjusting for cohort-relevant covariates.The distribution of maternal pre-pregnancy BMI was comparable across sites but differed by ethnicity and socioeconomic status. A positive linear association between maternal pre-pregnancy BMI and newborn offspring HTH MD was observed at both sites (These findings translate the preclinically established association between maternal obesity during pregnancy and offspring hypothalamic microstructure to the human context. In addition to further replication/generalization, future efforts to identify biological mediators of the association between maternal obesity and fetal HTH development are warranted to develop targeted strategies for the primary prevention of childhood obesity.The online version contains supplementary material available at 10.1186/s12916-023-02743-8. Childhood obesity is a major global public health challenge as it increases the likelihood of adverse obesity-related disorders in later life as well as their development at earlier ages  and withObesity is a highly multi-factorial phenotype , and theAnimal models suggest that the HTH exhibits developmental plasticity during the fetal period as it develops in the context of, and adapts to, variation in maternal overnutrition –20, whichuman HTH in the context of interindividual variation in maternal overnutrition remains limited, it is supported by at least two recent studies. First, we recently reported on an association between maternal circulating saturated free fatty acid concentration (sFFA) during pregnancy and newborn offspring HTH microstructure indexed using diffusion tensor imaging (DTI)-based mean diffusivity (MD), that, in turn, was prospectively associated with early childhood adiposity ) difference in infant HTH MD (HTH MD weighted average across cohorts). While the HTH MD phenotype used here is non-specific to the underlying microstructure, the observed direction of association  is consistent with several microstructural phenotypes of obesity that reduce barriers to diffusion including reduced axonal outgrowth , gliosisThe U.S. Endocrine Society has argued that obesity should be conceptualized as a disorder of the energy homeostasis  system , rather The two cohorts analyzed here differed in maternal age, gestational age at delivery, and pre-pregnancy BMI. Cohort differences in maternal age and gestational age at delivery were in the expected direction –41, and Several potentially confounding factors were associated with offspring HTH MD above and beyond maternal pre-pregnancy BMI, and these warrant further discussion. Within site 2, OB risk, maternal education, and maternal ethnicity were all associated with HTH MD. Notably, OB risk and maternal education were not associated with HTH MD within site 1, suggesting that these are not replicable and/or robust observations in the context of this study . However, because site 2 demonstrated a substantially higher prevalence of OB risk, and because maternal education measures may reflect different socioeconomic pressures in different settings, these issues likely warrant further investigation. Relatedly, while significant at both sites, the effect sizes of postnatal age at scan and global measures of MD were markedly different across sites despite similar central tendencies. One explanation for this discrepancy could be differences in sample homogeneity  where a larger proportion of variance is available for attribution to variance in maternal BMI. Alternatively, this observation could simply be due to differing approaches to handling low quality data wherein one excelled at removing measurement error relative to the other. Finally, the association between maternal ethnicity and offspring HTH MD suggesting lower neonatal HTH integrity among Hispanic neonates could not be tested at site 1 due to a high degree of ethnic homogeneity. However, because the direction of effect is consistent with higher rates of pediatric obesity among the Hispanic community , and becThe importance of identifying the role of BMI in the intergenerational transfer of obesity lies in its potential use as a screening tool for risk management . In addition, from the perspective of a developing fetus, BMI is representative of the diverse metabolic gestational milieu  in which the fetal brain develops. However, what BMI contributes in terms of representation, it lacks in specificity. That is, apart from generically informing policy and public awareness about the importance of maintaining a healthy pre-conceptional weight, this work provides limited insight into targeted interventions on the biological pathways of obesity risk transfer from mother to her offspring. For this reason, and because BMI alone is not always perfectly reflective of metabolic status , future efforts should aim to identify the specific ligands and conditions sufficient and necessary for the intergenerational transmission of obesity.Weight stigma is among the most pervasive forms of discrimination within society, and is associated with adverse psychological (depression) and physiological (stress) conditions linked to increased weight  gain. ItLimitations of this study include the focus on a relatively healthy population, lack of gestational biological data, limited spatial resolution, and lack of specificity provided by the outcome (MD). Class I obesity represented roughly 10% of the study population and thus this study is likely underpowered to draw obesity-specific conclusions. To address this shortcoming, future studies would benefit from oversampling class I obesity and above to further identify consequences for fetal development specific to the obese condition. The current study did not collect or consider several developmentally important maternal ligands including the feeding-related hormones leptin  and ghreIn conclusion, the findings from the current study represent a significant conceptual advance to the literature by providing translational evidence of a robust association between maternal pre-pregnancy BMI and newborn offspring hypothalamic microstructure . Importantly, because maternal BMI is potentially modifiable (at least in the short term) through diet, exercise , and/or Additional file 1: Table S1. More Parsimonious Model Site Comparison: Maternal Pre-pregnancy BMI and Offspring Hypothalamic (HTH) Mean Diffusivity (MD). Maternal Pre-pregnancy BMI is associated with offspring HTH MD in a more parsimonious model excluding adjustment for white matter mean diffusivity. Table S2. Parsimonious Model With Sex Interaction Site Comparison: Maternal Pre-pregnancy BMI and Offspring Hypothalamic (HTH) Mean Diffusivity (MD). No evidence for a sex-specific association between maternal pre-pregnancy BMI and offspring infant HTH MD at either site (p > 0.1).


Epichloë endophytes from mutualistic to parasitic. The change in symbiosis outcome would be explained by the negative effects of the plant physiological responses on the endophyte performance. Furthermore, we posit that endophytes may protect the mutualism by the induction of plant defence hormone responses and antioxidants.Plants commonly form mutualistic associations with fungal endophytes. We put forward the hypothesis, with supporting evidence, that certain plant physiological responses to stress [i.e. phytohormones and reactive oxygen species (ROS)] change the symbiosis between plants and Epichloë  caused by the disruption in the endophyte-derived benefits and growth of the symbionts within plant tissues . We descEpichloë-based production of alkaloids, diminish the herbivore resistance of symbiotic plants, and compromise the mutualism   phenotypes in symbiotic plants  than non-symbiotic plants exposed to the same treatment (whereas the endophyte did not affect the reproductive effort of plants not exposed to ozone)  that increase the fitness of symbiotic plants in situations of stress by phytopathogens (Achnatherum inebrians against the phytopathogen Blumeria graminis was increased by the presence of endophytes that boosted plant defences by inducing SA-related responses (Curvularia lunata pathogen was documented in A. sibiricum plants associated with endophytes that induced plant JA-related defence responses (Alternaria solani was shown in Solanum lycopersicum plants symbiotic with Serendipita indica root endophytes that primed JA/ethylene host defence responses (athogens . The resEpichloë can also enhance antioxidant levels that generally increase the fitness of symbiotic plants under stressors that increase ROS-associated oxidative damage (Elymus dahuricus plants was increased by the presence of endophytes that enhanced contents/activities of several antioxidants that reduced the oxidative damage within plant tissues (L. perenne plants was also increased by endophytes that enhanced the contents/activities of several antioxidants within symbiotic plants (e damage  (Ueno et tissues . SimilarHere we have highlighted that the effects of environmental stressors can compromise the mutualism between plants and endophytes by the induction of plant physiological responses. Whereas phytohormone- and ROS-related responses were considered independent here, in reality the whole-plant response to stresses involves the interaction between both pathways (


Although a large number of studies have shown brain volumetric differences between men and women, only a few investigations to date have analyzed brain tissue volumes in representative samples of the general elderly population.We investigated differences in gray matter (GM), white matter (WM) and intracranial volumes (ICVs) between sexes in individuals above 66 years old using structural magnetic resonance imaging (MRI).Using FreeSurfer version 5.3, we automatically obtained the ICVs, GM and WM volumes from MRI datasets of 84 men and 92 women. To correct for interindividual variations in ICV, GM and WM volumes were adjusted with a method using the residuals of a least-square-derived linear regression between raw volumes and ICVs. We then performed an ANCOVA comparing men and woman including age and years of schooling as confounding factors.Women had a lower socioeconomic status overall and fewer years of schooling than men. The comparison of unadjusted brain volumes showed larger GM and WM volumes in men. After the ICV correction, the adjusted volumes of GM and WM were larger in women.After the ICV correction and taking into account differences in socioeconomic status and years of schooling, our results confirm previous findings of proportionally larger GM in women, as well as larger WM volumes. These results in an elderly population indicate that brain volumetric differences between sexes persist throughout the aging process. Additional studies combining MRI and other biomarkers are warranted to identify the hormonal and molecular bases influencing such differences.


Although rural-to-urban migration has been well researched, how gender shapes processes and outcomes, including later life health outcomes, has not been thoroughly investigated. Guided by a life course perspective, this study explores gender differences in rural-urban migration patterns and its association with mental health in later life among Chinese older adults. Exploiting rich life history data from the China Health and Retirement Longitudinal Study, we employ sequence analysis to identify the typical migration trajectories of Chinese older adults. Moderated mediation analysis is then used to examine gender-specific health pathways linking migration trajectories and later-life mental health. The results indicate that: men and women follow different migration trajectories across the life course. Men are more likely to migrate between rural and urban areas, and to migrate multiple times. Rural migrants who settled in urban regions have better mental health in later life than return migrants or rural non-migrants; the gender gap in mental health is marginally smaller among early urban settlers than rural non-migrants. Household income and Hukou conversion mediate the relationship between migration trajectories and later-life mental health among older people of rural origin. Household income in later life has stronger mediation effects for migrant men than for migrant women. The study suggests that a life course perspective and awareness of gender dynamics should be incorporated in policymaking to reduce the rural-urban divide and gender-based inequality in mental health.


Prejudice, stigmatization and discrimination behaviors causes social stress and lead vulnerability to mental and physical health problems in Transgender and Gender Nonconforming (TGNC) individuals. The prevalence of mental disorders that can be associated with “minority group stress”, especially major depression and anxiety disorders, are known to be higher in the TGNC group in comparison to general population.The aim of this study was to reveal the impact of minority stress on TGNC individuals’ mental health. Resilience factors like gender identity pride, social support, community connectedness expected to diminish the negative impact of stigmatization and discrimination.The study sample consisted of 48 volunteered participants who consulted to Psychiatry Department for gender transition process. After semi-structured interview, applicants were given Gender Minority Stress and Resilience Scale-Turkish Form (GMSR-Tr), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS), Multidimensional Scale of Perceived Social Support (MSPSS).s= .727), BAI , PSS . For psychological resilience, the strongest positive relationship was found with the community connectedness subscale ; the strongest negative relationship was observed with the internalized transphobia subscale .Analysis revealed a negative correlation between the stress subscales of GMSR-Tr scale and BDI (p< .001; rOur study presented the importance of internalized transphobia and protective effect of resilience factors for mental health outcomes of TGNC individuals exposed to minority stress. The depression, anxiety and stress scores decreases with increasing psychological resilience.


Given the onset of COVID-19, older adults who recently lost their significant others feel more stressed. There yet exist a study utilizing smartphones for web-based delivery of mindfulness intervention among bereaved older adults. Therefore, this study aimed to test the initial efficacy of an app-based mindfulness-meditation (AMM) to alleviate stress and depressive symptoms and improve stress resistance, social support, and self-esteem in Korean older adults experiencing bereavement. Participants included 22 Korean older adults who had been bereaved within the preceding year. AMM involved sound therapy, breathing exercises, and narrated meditation sessions, and the program was conducted over eight weeks. The linear regression results showed that stress level among participants was significantly lower after the intervention, with decreased scores from the baseline. By confirming that AMM is an effective way of reducing stress, more active usage of devices like smartphones should be promoted to develop mental health interventions for older adults.


We later discuss the necessity to update the current GEA models to predict both regional- and local- or micro-habitat–based adaptation with mechanistic ecophysiological climate indices and cutting-edge GWAS-type genetic association models. Furthermore, to account for polygenic evolutionary adaptation, we encourage the community to start gathering genomic estimated adaptive values (GEAVs) for genomic prediction (GP) and multi-dimensional machine learning (ML) models. The latter two should ideally be weighted by de novo GWAS-based GEA estimates and optimized for a scalable marker subset. We end the review by envisioning avenues to make adaptation inferences more robust through the merging of high-resolution data sources, such as environmental remote sensing and summary statistics of the genomic site frequency spectrum, with the epigenetic molecular functionality responsible for plastic inheritance in the wild. Ultimately, we believe that coupling evolutionary adaptive predictions with innovations in ecological genomics such as GEA will help capture hidden genetic adaptations to abiotic stresses based on crop germplasm resources to assist responses to climate change.Leveraging innovative tools to speed up prebreeding and discovery of genotypic sources of adaptation from landraces, crop wild relatives, and orphan crops is a key prerequisite to accelerate genetic gain of abiotic stress tolerance in annual crops such as legumes and cereals, many of which are still orphan species despite advances in major row crops. Here, we review a novel, interdisciplinary approach to combine ecological climate data with evolutionary genomics under the paradigm of a new field of study: genome–environment associations (GEAs). We first exemplify how GEA utilizes Letter to Karl Freiesleben, June 1799.“I shall endeavor to find out how nature’s forces act upon one another, and in what manner the geographic environment exerts its influence on animals and plants. In short, I must find out about the harmony in nature” Alexander von Humboldt— Crop wild relatives (CWR) and landraces are well known for providing new alleles for plant breeding . They alVigna subterranea), chickpea (Cicer arietinum), cowpea (V. unguiculata), grass pea (Lathyrus sativus), groundnut (Arachis hypogaea), marama bean (Tylosema esculentum) (Lupinus mutabilis) (Phaseolus acutifolius) , sorghum (Sorghum bicolor), and finger millet (Eleusine coracana) or pearl and proso millets . Many of these crops have interesting drought-tolerance traits and some capacity to grow in compacted soils. Cowpeas, groundnuts, and lesser known cereals are already traditional food sources and biocultural components for vulnerable areas, especially in Sub-Saharan Africa and parts of Asia and Latin America  , tarwi (tabilis) , and tepifolius)  constitu America .Yet, despite their tolerance to drought and heat plus their high nutritional quality, the utilization of these orphan crops is limited partly because of the poor characterization of their genetic background . TherefoStill, a major question to harness crop prebreeding for climate change pressures is whether there is enough heritable variation in traits associated with tolerance to abiotic stress. In this context, genomic characterizations of reference collections comprising CWR, landraces, and orphan crops that span contrasting habitats offer a straightforward scenario to identify natural standing adaptation to abiotic pressures .The spirit behind this novel approach is to detect genomic regions that correlate with habitat heterogeneity as an indication of the natural selection imprint to environmental gradients . Since tGlycine  WCR; or For orphan crops, rather than nondomesticated natural plant species, fewer GEA studies have been undertaken. Although still limited to the easier-to-grow annual grain species compared to perennial and root/tuber crops, GEA is starting to make important contributions to genetic analysis of landraces and WCR germplasm, often richly represented in the world’s major gene banks for crop species. The analytical pipeline for GEA studies is shown in Historically, based on the technological improvements in sequencing and SNP detection and as a means to improve GEA, the field has moved from the candidate gene approach  into fulin situ ecological georeferencing of accessions, and by 2) revealing the genomic architecture of adaptation via cutting-edge predictive models  using georeferencing and statistical downscaling  and machine learning (ML) , capableOverall, CWR and landraces undeniably harbor unique adaptations to abiotic stresses, rarely present in the cultivated and improved genepools . HoweverGP works either on the basis of shared relatedness  or on the basis of linkage disequilibrium (LD) between the SNP marker loci and the genetic variants that underlie phenotypic variation . The relThe predictive ability of GP models may be further biased depending on whether the entire SNP set is used, or the most predictive SNP data are chosen after the GWAS-type analysis , the latde novo GWAS-based GEA estimates gathered from other (or even the same) panels (Better approaches to be implemented and reported include 1) weighted GP models using ) panels  and 2) o) panels . GP can ) panels . GEAVs c) panels  would be) panels , high-th) panels , and ML-) panels .Next-generation GEA models and GEAVs will allow the use of “exotic” parents for targeted predictive prebreeding in crop species. They offer feasible methodologies to trace the sources of abiotic stress adaptation and tolerance targeting crop resources in low-income countries, which are also the most vulnerable to climate change. Here, we have discussed strategies to implement the latest-generation predictive e.g.,  and genoModern GEA approaches will allow further studies of evolutionary conservatism, parallelism, and convergence in the genetic architecture of adaptation to various types of abiotic stresses across a wide range of environments, landraces, and wild accessions . ApproacHow genetic diversity and genomic divergence arise and are shaped based on ecological pressures is one of the main questions in molecular evolution  and has ST statistic (A). Once the potential confounding demographic patterns have been accounted for, it is then feasible to disentangle genuine signatures of environmental adaptation (B) from spurious concurring genetic drift due to genomic constraining features. Finally, these combined summary statistics  can ultimately redound in prebreeding efforts aiming to introgress exotic adaptive variation into elite lines (C), for instance, via backcrossing (BC) schemes for abiotic and biotic stresses.Therefore, GEA efforts can be enhanced by exploring SNP density and statistics of site frequency spectra  in associated vs. nonassociated regions . Figure ad hoc multiple hypotheses  to which scale epigenomic marks  regulatand sRNA , and mayeritance , eventuaeritance .e.g. GEAVs), as well as the identification of underlying factors that may facilitate or constrain future adaptive responses to changing climate.Ultimately, GEA is empowering the understanding on how plant genomes interact with their environment while shaping adaptive phenotypes. Such mechanistic insights of the genome functionality in the wild promise leveraging the characterization of landraces and CWR to assist prebreeding efforts through multi-dimensional adaptive scores (Lastly, GEA studies offer new possibilities to efficiently unlock crop diversity for climate adaptation . Unexplo


In preclinical animal models, researchers can, within the same thin slice of tissue, probe activity within neurons [e.g., immediate early gene protein products  and deprivation  on stria terminalis white matter  and function  have a reciprocal relationship that facilitates global and integrative brain processes  and found connection features that distinguish preterm and term-born infants. Their approach revealed novel insights into the global manner in which preterm birth impacts neurodevelopment, identifying local intra-network functional connections and long-range inter-network structural connections that differentiate between pre-term and term-born infant brains.In this current Research Topic, authors demonstrated the breadth of how multimodal neuroimaging can surpass unimodal neuroimaging across developmental, clinical and methodological domains. Zhu et al. presented new methodology featuring brain network construction under a unified framework of joint fMRI and DWI . Their method considered relationships between multiple brain regions and a PageRank algorithm that extracts significant node information from the unified network. Zhu et al. applied their method to a clinical problem—classifying epilepsy diagnoses, comparing normal controls (NC), frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). Their methods achieved the highest classification accuracy compared to unimodal methods when classifying against NC and achieved among the highest accuracies when classifying FLE v. TLE.Tang et al. developed a new interpretable hierarchical graph representation learning framework for brain network regression analysis using multimodal MRI data. They used this approach to predict a variety of affective, somatic, cognitive and behavioral measures and found that the proposed framework achieved the best performance compared to baseline methods; this was attributed to extraction of graph local structures as low-level features and preservation of these into high-level space hierarchically.Sun et al. developed new methods that capitalize on synergies between PET and DWI data, using DWI-derived structural connectivity and PET intensity to denoise PET images. Their CONNectome-based Non-Local Means (CONN-NLM) filter provides more informative denoising by weighting similar-intensity PET voxels and highly connected voxels more heavily. This yielded greater PET image quality and lesion contrasts and produced superior denoising effects compared to filters not utilizing DWI data.Babaeeghazvini et al. reviewed the convergence of structure and function with associations between white matter microstructure and electro-encephalography (EEG). They note that white matter microstructure may influence the velocity of communication between brain regions and across hemispheres, and that amplitudes and latencies of event-related potential components may reflect pathological differences in structure; yet, the diversity of findings calls for more standardization of EEG analysis.Finally, To conclude, the field would benefit significantly from effective use of multimodal approaches in the methods development space and in basic, clinical and translational research. This requires open science and enhanced accessibility of tools that process and analyze multimodal neuroimaging data. Future directions can include enhanced integration of “neurochemical” imaging modalities  with structural and functional modalities. The reports highlighted in this topic are an excellent demonstration of how multimodal approaches can improve methodologies, predictive power and clinical classification abilities to ultimately identify neural markers of psychopathology risk and guide more targeted treatments.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Scientific Reportshttps://doi.org/10.1038/s41598-021-03727-5, published online 20 December 2021Retraction of: The Editors have retracted this Article.there is insufficient justification for the grouping of the patients who belong to clinically heterogeneous cohorts with multiple different psychiatric disease presentations;the study lacks objective outcome measures; andthere are concerns about the validity of the therapeutic intervention tested—specifically that Tenoten contains antibodies diluted beyond the point at which any active molecules are expected to be present and there is no molecular analysis to support the presence of molecules at these dilutionsAfter publication of this Article concerns were raised regarding the design of the study and the robustness of its central conclusions. Post-publication peer review has confirmed that:The Editors therefore no longer have confidence in the conclusions presented.Vladimir Anatolevich Parfenov, Dina Rustemovna Khasanova, Pavel Rudolfovich Kamchatnov and Alexey Borisovich Glazunov disagree with this retraction. Enver Ibragimovich Bogdanov, Tatiana Markovna Lokshtanova, Aleksandr Vitalevich Amelin, Natalya Nikolaevna Maslova, Nataliia Vyacheslavovna Pizova, Galina Nikolaevna Belskaya, Evgeny Robertovich Barantsevich, Gulsum Abdurahmanovna Duchshanova, Saltanat Ualihanovna Kamenova and Oleg Vladimirovich Kolokolov did not respond to correspondence from the Editors about this retraction.


Racial and ethnic health disparities are fundamentally connected to neighborhood quality. For example, racial and ethnic minorities are more likely to live in neighborhoods with signs of physical disorder , and physically disordered environments have been noted to associate with increased risk for chronic illness. Given that older adults may spend more time in their neighborhoods than younger adults as they transition out of the workforce, examining associations between neighborhood physical disorder and health among older minorities is of critical importance. Using 2016-2018 Health and Retirement Study (HRS) data, a representative sample of US adults aged 51 years and older , we conducted a series of weighted linear regressions to examine links between neighborhood disorder as rated by third parties and both participant-perceived neighborhood safety and self-rated health. Study results indicated that higher neighborhood physical disorder was significantly related to more neighborhood safety concerns among non-Hispanic White and Hispanic residents, but not among non-Hispanic Blacks. On the other hand, neighborhood physical disorder was significantly associated with poorer health among all racial/ethnic groups. These patterns persisted after adjusting for education, sex, age, and census tract concentrated disadvantaged, population density, and racial/ethnic diversity. Our results indicate that community level interventions targeting neighborhood physical disorder may improve community health and minimize racial/ethnic health disparities.


Additional abnormal uptake in the right axillary artery, aortic arch, and left femoral artery corresponded to the insertion sites for arterial inflow during cardiopulmonary bypass. Knowledge that FDG accumulation may occur at the insertion sites of an extracorporeal-circulation device enables unnecessary tests to be avoided.A 37-year-old man with previous heart transplantation for dilated cardiomyopathy underwent screening for malignancy under posttransplantation immunosuppression.


Health inequalities partially remain due to differences in diet between socioeconomic groups. Examining the association between socio-ecological factors and the diet of socioeconomically disadvantaged (SED) individuals can enhance the development of interventions to decrease health inequalities.In total, 278 SED adults residing in two Flemish municipalities completed a survey addressing sociodemographics, diet, health and their perceptions of the food environment. The objective food environment was examined by assessing food retailer information in street network-based buffers of 500m and 1000m around participants’ addresses. Linear regression was used to test assumptions.Individual factors such as poor subjective health , food insecurity  and living alone  were negatively associated with healthy dietary habits such as daily fruit and vegetable (FV) consumption. Positive perceptions on the availability of FV were positively associated  with daily FV consumption. Objective food environmental factors showed a stronger association with unhealthy dietary habits. A greater amount of retailers within 1000m walking distance was negatively associated with fast-food  and sugar-sweetened beverages (SSB) consumption . More supermarkets within 500m distance was negatively associated  with SSB consumption, while more convenience stores within a 1000m distance was positively associated  with SSB consumption.Our findings suggest that factors associated with the diet of SED adults differ according to food and drink items. Interventions focused on this population should take these differences into account.Individual and food environmental factors are both associated with the diet of socioeconomically disadvantaged adults but differ according to food and drink items.Individual factors and perceptions of the food environment more likely associated with a healthy diet. Objective factors of the food environment were more likely associated with an unhealthy diet.


Impaired reproductive health is a worldwide problem that affects the psychological well-being of a society. Despite the technological developments to treat infertility, the global infertility rate is increasing significantly. Many infertility conditions are currently treated using various advanced clinical approaches such as intrauterine semination (IUI), in vitro fertilization (IVF), and intracytoplasmic injection (ICSI). Nonetheless, clinical management of some conditions such as dysfunctional endometrium, premature ovarian failure, and ovarian physiological aging still pose significant challenges. Stem cells based therapeutic strategies have a long-standing history to treat many infertility conditions, but ethical restrictions do not allow the broad-scale utilization of adult mesenchymal stromal/stem cells (MSCs). Easily accessible, placental derived or amniotic stem cells present an invaluable alternative source of non-immunogenic and non-tumorigenic stem cells that possess multilineage potential. Given these characteristics, placental or amniotic stem cells (ASCs) have been investigated for therapeutic purposes to address infertility in the last decade. This study aims to summarize the current standing and progress of human amniotic epithelial stem cells (hAECs), amniotic mesenchymal stem cells (hAMSCs), and amniotic fluid stem cells (hAFSCs) in the field of reproductive medicine. The therapeutic potential of these cells to restore or enhance normal ovarian function and pregnancy outcomes are highlighted in this study. Over the past few daces, a substantial decline in fertility rate is observed around the world . Both ecDespite the availability of cutting-edge therapies to restore or enhance infertility, some pathological conditions such as the dysfunctional uterus, persistent atrophic/thin endometrial lining, and loss of regeneration capacity of endometrial tissue lower the success rate of these treatments. For instance, successive embryo implantation failure due to a dysfunctional uterus or immune rejection remains the main reason for IVF treatment failure. Similarly, the inefficient process of endometrial tissue regeneration due to the loss of stem cells in the basalis layer of endometrium leads to pathological conditions such as intrauterine adhesion (IUA) or endometrial atrophy. Stem cell-based regenerative therapies hold the great capability of replenishing the functional deficit cell reservoir to address such pathological conditions .Due to the differentiation ability into germ cells and oocyte-like cells, stem cells may adopt the following mechanisms to repair ovarian functions; i) heal injured reproductive tissues by replenishing healthy cells, ii) restore or increase the number of secondary and mature follicles, iii) improve microenvironment by secreting paracrine factors and ameliorate ovarian function, iv) immune regulation by secreting anti-inflammatory factors, and v) regulate the hormonal levels that maintain estrous reproductive cycles and stimulate ovulation such as E2 (Estradiol), AMH (Anti-Müllerian hormone), and FSH (Follicle-stimulating hormone). Despite the great success of stem cell therapeutics in reproductive disease management, the ethical concerns, heterological nature, low yield, and lower ex-vivo proliferation rate of adult stem cells limit their clinical translation . ConversStem cells isolated from the umbilical cord have well-established therapeutic uses and are discussed in literature excessively . Other eMesenchymal stromal/stem cells (MSCs) derived from the avascular mesenchymal matrix of the human amniotic membrane (hAM) offer a beneficial option to replace adult MSCs –11. LimiThe studies that explored the role of hAMSCs to promote ovarian function in natural or premature ovarian aging (NOA or POA) or premature ovarian failure/inefficacy (POF/POI) mouse models are listed in Table γ, TNFα), induction of anti-inflammatory molecules (TGF-ß), and regulation of the Treg cell population were found critical in improving the number of glands and reducing fibrotic areas in ovaries [Yin et al.  and Gan  ovaries .In vivo studies demonstrated that hAMSCs harbor the great ability to colonize uterine tissue and ovarian stroma which helps achieve the utilization rate of hAMSCs thus the desired outcomes. However, various strategies were adopted and compared to improve the homing of stem cells, e.g., repeated vs. single transplantation of hAMSCs , direct In a few comparative studies, the therapeutic potential of hAMSCs in recovering ovarian functions was found superior to other cells such as hAECs , 26 or aThese inherent characteristics of hAMSCs suggest multiple clinical applications in the field of reproductive biology. However, due to the lack of human studies, clinical uses of hAMSCs are mostly theoretical until now and need further optimization in the preparation and banking procedures.Human amniotic epithelial stem cells (hAECs) have been entertained as another possible source of endometrial regeneration or restoring ovarian function. The hAECs comprise a major portion of the epithelial cell layer of the basement membrane of hAM. The stem cell markers expression profile of hAECs, i.e., CD73, CD90, and CD105 positive, while negative for hematopoietic markers CD34 and CD45) is remarkably similar to MSCs. Howeverβ/Smad signaling pathway that resulted in a reduction of cell apoptosis thus improving follicle formation [Wang et al.  performeormation –34.Until now, only two studies have assessed the therapeutic efficiency of hAECs for the treatment of IUA Table . Li et aInfertility or obstetrical infertility complications may occur after cesarean section due to injury to the endometrium and subsequent collagen deposition. In a recent study, the hAECs were used to treat cesarean scar defect (CSD) conditions in a rat uterine scar model . After 3Amniotic fluid is enriched with different types of stem cells in all three phases of pregnancy. Stem cells derived from human amniotic fluid (hAFSCs) are characterized by well-established stem cell surface markers , 40. AFSWhile still in an early stage of development, hAFSC-based in vivo studies show promising results to preserve follicle cells and prevent ovarian dysfunction Table . In a stIn a recent study, mesenchymal stem cells from amniotic fluid (hAFMSCs) were explored to study their potential and mechanism to rescue ovarian senescent cells . The amnGiven the ease and availability of placental membranes, which are considered a medical waste following delivery, unexpectedly no clinical studies have been published evaluating the role of amniotic-derived stem cells in restoring ovarian functions in humans. Similar to other fields of medicine, the inherent properties of ASCs warrant their success in the setting of endometrial-driven, chemotherapy-induced, or age-related infertility. However, based on studies reported so far, significant challenges still exist before the translation of these cells in clinical studies. Such as addressing the successful differentiation of ASCs in germ cells in culture, defining the route and time of administration of cells to increase effectiveness, use of precise animal models, and addressing long-term fertility benefits. Future studies should continue to elucidate regulatory mechanisms induced by the amniotic stem cells in ovarian recovery for successful manipulation of these cells in treating infertility.Amniotic tissue or fluid-derived human amniotic cells  exhibit stem cell properties with low immunogenicity or tumorigenesis making them theoretically superior to other stem cells. Many studies were performed using mouse models of chemotherapy treated premature ovarian failures, age-related ovarian failure, or other related infertility pathological conditions. These in vivo investigations reported the fundamental findings to understand the mechanisms of actions of ASCs in restoring fertility outcomes. These studies suggest that ASC transplantation promotes follicle formation, endometrial regeneration, glandular development, and restores hormone levels . These physiological improvements are carried out due to paracrine, anti-inflammatory, and immune regulatory properties of ASCs. Although these studies provide a theoretical foundation for their application in infertility-related health issues, future studies are warranted to confirm these results for their successful translation into clinical applications.


An 80-year-old Caucasian female patient presented with a two-year history of intensively itching skin rash located on her left lower leg and mild swelling of the proximal interphalangeal and metacarpophalangeal joints, accompanied by morning stiffness around these joints, lasting at least one hour before maximal improvement . She repPresence of intensively pruritic erythematous papules located on the left pretibial surface was established clinically . SymmetrImmunological testing for antinuclear antibody (ANA) and Scl 70 was negative. The cutaneous pathological changes presented required a wide spectrum of differential diagnoses, including pretibial myxedema, necrobiosis lipoidica, the small papular form of cutaneous sarcoidosis, T-cell lymphoma, lichen ruber planus and Arndt-Gottron scleromyxedema. Histopathological evaluations on skin biopsies revealed hyperkeratosis, focal acanthosis, subepithelial structures that stained pink with hematoxylin-eosin and mild to moderate mononuclear infiltrate around single vessels . SubepitThe findings were characteristic of amyloid deposition and a diagnosis of lichen amyloidosis was made. No clinical or laboratory evidence of systemic amyloidosis was presented. Systemic therapy consisting of bilastine (20 mg daily) and acitretin (15 mg daily) was started, with topical application of 0.1% mometasone furoate cream, which produced a satisfactory therapeutic response. The patient was referred to a rheumatological unit for further therapy with biological agents.Localized cutaneous amyloidosis encompasses several conditions characterized by deposition of amyloid or amyloid-like proteins in the dermis, including macular amyloidosis and lichen amyloidosis.Lichen amyloidosis is a primary form of localized cutaneous amyloidosis that is clinically manifested through hyperkeratotic erythematous to brownish papules, while amyloid deposition can be seen via specific histological staining in previously normal skin without any evidence of visceral involvement.Although cutaneous lesions may be seen in up to 40% of patients with primary and myeloma-associated systemic amyloidosis, their presence results from tissue deposition of immunoglobulin light chain material derived from a circulating paraprotein.,Although the etiology is not fully understood, chronic irritation to the skin has been proposed as possible etiological factor.,,Treatment options include potent topical steroids under occlusion, intralesional steroids, topical dimethylsulfoxide and etretinate.We have described a rare association between lichen amyloidosis and rheumatoid arthritis in an 80-year-old female patient, without evidence of systemic amyloid involvement. To the best of our knowledge, this is the first reported case of primary cutaneous amyloidosis in a patient with rheumatoid arthritis, in contrast to the much more frequent association of rheumatoid arthritis with systemic amyloidosis, the pathogenetic relationship remains unclear. It is also unclear whether lichen amyloidosis might be the first clinical manifestation of the initial systemic involvement, in which cutaneous lesions can be seen in up to 40% of the patients,


The use of selectiveserotonin reuptake inhibitors (SSRIs) is an independent risk factor for bleeding events. Antidepressants and oral anticoagulants (OACs) are often prescribed together as depression and anxiety often coexist with cardiovascular diseases, atrial fibrillation and thromboembolic disorders. Serotonin is released from platelets in response to vascular injury, promoting aggregation. Inhibition of serotonin transporter (responsible for the uptake of serotonin into platelets) can lead into a reduced ability to form clots and a subsequent increase in the risk of bleeding. Direct oral aticoagulants (DOACs), rivaroxaban, apixaban and edoxaban are primarily metabolized via CYP3A4. The co-administration of antidepressants with inhibitory effects on CYP3A4 may theoretically interact with them.Presentation of a case of upper gastrointestinal bleeding after initiation of Apixaban in a patient taking Sertraline and literature review.We carried out a literature review in Pubmed electing those articles focused on bleeding risk between newer direct oral antigulants and selective serotinin reuptake inhibitors.A 66-year-old woman sought medical assistance for generalized ecchymosis and melena. She was diagnosed with atrial fibrillation treated with apixaban 7 days ago. Concomitant treatment between apixaban and sertraline was the possible cause of upper gastrointestinal bleeding and ecchymosis. We had to switch sertraline into vortioxetine (with less dregree of serotonin reuptake inhibition) and add proton-pump inhibitor (Omeprazole) in order to decrease the risk of bleeding.SSRIs increase the risk of gastrointestinal bleeding, much more in case of concomitant use of oral anticoagulants. If SSRI use cannot be avoided, monitor closely and prescribe proton pump inhibitors.


Past research shows that discriminatory experiences may reduce sense of purpose among older adults, though these associations are inconsistent across groups. Work is needed both to understand the nuanced role discrimination plays on individuals’ sense of purpose, whether it leads to feeling derailed from life goals, and if effects differ for younger versus older adults. The current study asked 354 American adults (age 19-74) to complete daily surveys over the course of two weeks, to examine whether experiencing discrimination during that two-week period led to a decline in purposefulness. Overall, findings suggest marked stability in sense of purpose during this short timeframe. However, greater daily discrimination predicted decreases in sense of purpose, and increases in derailment over the two weeks. While these associations were similar across age, older adults did report less discrimination at baseline. Findings will be discussed with a focus on successful aging among marginalized groups.


Individuals with substance use disorders are considered unpredictable and violent by the public. Besides, health care workers (HCW) may have negative attitudes towards them, despite their knowledge about addiction; which is related to lower quality of care. In Turkey, addiction service users are predominantly male, over ninety percent; while women make up a large percentage of psychiatrists.The present study aims to evaluate if the HCWs level of stigma towards individuals with substance use disorder changes due to gender and mental health sector experience of the HCWs.Within an online survey, participant HCWs answered Attitudes Towards Treatment of Substance Use Disorders Scale, Substance Addiction Stigmatization Scale, Alcohol Addiction Stigmatization Scale; in addition to sociodemographic questions.Three hundred ninety-eight HCWs were included in the analyses. 22.7% of them (n=91) were recruited in mental health sector. Mental health care workers had lower levels of stigma towards individuals with alcohol use disorders  and substance use disorders  and, lower levels of stigma towards addiction treatments . Among mental health care workers, women scored higher numbers of stigmatization towards alcohol use disorder and addiction treatments . On the other hand, women and men in other HCWs groups did not differ from each other in terms of stigmatization measurements The gender of mental health care workers may be related to stigmatization towards addictive disorders. Future research should evaluate underlying factors.No significant relationships.


Despite well-recognised benefits, Irish breastfeeding rates remain suboptimal. Although associations between breastfeeding and allergic disease are well-researched in younger children, evidence for continued effect in older children is sparse. This Irish prospective cohort study investigated associations between breastfeeding and allergic disease at age nine.The study sample included all nine-year-old children enrolled in the Growing Up in Ireland Infant Cohort Study whose mothers had participated in both Wave 1 and Wave 5. Mothers self-reported infant feeding practices at nine months and allergic diseases at nine years. Multiple logistic regression was used to generate adjusted odds ratios (aOR) for associations between breastfeeding and allergic diseases; re-weighting was applied to enhance generalisability.Response rate was 72% . Most mothers (53%) had ever-breastfed their child; younger mothers, smokers and those of lower socioeconomic status were significantly less likely to have ever-breastfed. Compared to never-breastfeeding, ever-breastfeeding was protective against asthma  and eczema  at age nine. Ever-breastfeeding increased the risk of atopic rhinitis ; the association with food allergy was inconclusive . Breastfeeding ≥6 months was protective against asthma  and any allergic disease . Exclusive breastfeeding (3-5 months) was protective against asthma  and eczema .This study provides new evidence suggesting breastfeeding may be protective against asthma and eczema but may increase the risk of atopic rhinitis in older Irish children. Results must be considered in light of high Irish allergic disease prevalence and action in support of breastfeeding prior to and following birth prioritised accordingly.Findings lend support to a protective association between breastfeeding and asthma and eczema in later childhood and indicate breastfeeding may play a role in allergic disease prevention.Breastfeeding may reduce the risk of asthma and eczema in Irish children: findings should be used to drive impactful breastfeeding promotion and reorientate cultural norms in favour of breastfeeding.


Medicaid home and community-based services (HCBS) provide integral health-related and personal care to support community-dwelling older adults. Growing literature suggests that states with more generous HCBS expenditures may delay or substitute costly nursing home care, but evidence is limited on the impact of HCBS spending on transitions to residential care settings like assisted living. This study determines the association of state Medicaid HCBS generosity—HCBS spending as a percent of total long-term services and supports expenditure—on the probability of incident transitions to residential care settings or nursing homes. Publicly available HCBS expenditure data was linked to a nationally representative sample of 7,197 community-dwelling older adults participating in the National Health and Aging Trends Study from 2011-2018. A discrete-time, competing risk regression model estimated the association between HCBS generosity and transitions from community to residential care settings or nursing homes, adjusting for sociodemographic, socioeconomic, and health factors. Most older adults remained in the community (93.7%). Incident transitions into residential care settings were twice as likely to occur compared to transitions to nursing homes . Older adults residing in states with higher HCBS generosity (one percentage point increase) are less likely to transition to nursing homes . Greater HCBS generosity was not associated with transitions to residential care setting. Assessing HCBS generosity on transitions elucidates important contextual factors affecting the movement of older adults across the care continuum.


Physical intimacy is assumed to benefit well-being through stress-buffering and mood-improving processes. Although partnered older adults often report wishing for and experiencing physical intimacy, inquiries about how intimacy is linked to affect and stress in older couples’ daily lives remain scarce. We examined self-report and salivary cortisol data from 120 German couples  obtained up to seven times per day over seven consecutive days. In moments when participants experienced more physical intimacy, women reported less negative affect, and men more positive affect. Experiencing more overall physical intimacy was associated with more positive affect and less negative affect in women, and lower daily cortisol in men. More overall intimacy wished was related to more negative affect in women and men, and to higher daily cortisol in men. We conclude that physical intimacy relates to indicators of well-being in older couples’ daily lives and consider routes for future inquiry.


These neuroinflammatory processes serve to protect or remove degenerative cells and attempt to clean out amyloid plaques. Can AD-affected neurons contribute with a malfunctioning protein degradation mechanism to this process? A recent elegant study by Lee and coworkers5 has analyzed in several genetic mouse models of AD the major cytoplasmic recycling process of cells termed autophagy.Alzheimer’s Disease (AD) with synaptic dysfunction and cognitive decline is a devastating age-associated neurodegenerative disease accounting for about two thirds of all cases of dementia.5 which subsequently fuse with endosomes and eventually lysosomes (autolysosomes) for content degradation and its release for recycling  and expand the cellular membranes to blebs. Such PANTHOS-containing neurons were identified by the authors in post-mortem human AD brain samples as well.β-peptide deposition, is transported to the membrane through the secretory pathway along the endomembrane system,1 thus ER incorporation into PANTHOS structures provides these autophagic vacuoles with significant amounts of APP that can be proteolytically processed in endosomes/lysosomes. Strikingly, Lee et al. demonstrate that PANTHOS structures contain amyloid plaques with increasing levels of maturation over time concomitant with a compromised neuronal morphology.APP, the source of AEarly PANTHOS-containing neurons are not associated with reactive astrocytes or activated microglia. Therefore, initial autophagic defects, deacidified autolysosome accumulation, PANTHOS build-up and initial plaque formation evades detection by inflammation-mediating neighboring cells. Only when PANTHOS-containing neurons lose structural integrity, they are surrounded by activated astrocytes/microglia. At this advanced stage PANTHOS-containing neurons merge to larger structures likely giving rise to extracellular senile plaques that are eventually released into the extracellular space of the brain.4 Consequently, plaque formation should be viewed primarily as a cell-autonomous rather than a non-cell autonomous process.These findings of the authors imply several ground-breaking new insights into the possible mechanism of AD-associated plaque formation. Foremost, amyloid plaque formation considered to occur extracellularly due to APP proteolysis turns into an intracellular process followed by a release of already formed and matured plaques into the extracellular environment.The generation and accumulation of deacidified autolysosomes occurs long before histological signs of plaque formation and at stages when neurons appear to be healthy at large. This cellular metabolic signature could probably be exploited for diagnostic purposes of initiating AD or related neurodegenerative diseases at stages when preventive measure would still have major effects.Based on the author’s finding the view on neuroinflammatory mechanisms in association with AD may be seen from a different perspective. The first contribution of reactive glia to AD progression may be a late one, when amyloid plaques have already formed and matured inside PANTHOS-containing neurons. But by promoting neuronal cell death of late-stage PANTHOS-neurons, glia might serve as a can opener causing the release of plaque material into the brain environment. This would promote plaque spread, turns further plaque growth from an intracellular into an extracellular process and enables plaque contact and influence possibly with glia.Besides providing crucial novel insights into cell biological processes of amyloid plaque formation, like any exciting research new important question arise. What is so far missing, is a careful assessment about the role of neuroinflammation, since the authors did not elucidate precisely when neuroinflammation starts and what it contributes to the observed phenotype. It also remains unclear which mechanism mediates reduction in vATPase-activity, and why some autophagosomes are poorly acidified, while others show a properly acidic pH-milieu. Autophagy is a process common to all cells. Why are cholinergic neurons of the forebrain affected first by AD, are they more sensitive to PANTHOS formation? Reestablishing proper acidic conditions in poorly acidified autolysosomes in AD mouse models at early stages should prevent PANTHOS-formation and subsequent establishment of histological features as well as AD symptoms in these animals. Such a rescue would further provide evidence that amyloid plaque formation is initiated in a cell-autonomous process by autophagy defects in neurons themselves. This could trigger a plethora of new drugs or even the development of preventive strategies.Neurofibrillary tangles as a hallmark of late AD stages do not appear in PANTHOS-neurons until stages of their destruction. Are these deficits inherent to the genetic mouse models that are unable to phenocopy NFT formation like in human AD brains? To investigate the relationship between PANTHOS-forming processes and neurofibrillary tangle appearance will be an interesting area of research.1 strongly support the notion that, months before plaques develop, Aβ accumulates in faulty lysosomes neurons, and that this finally disturbs neuronal functioning and might cause neuronal death, leaving behind amyloid plaques. This supports therefore the hypothesis that lysosome dysfunction is an early, causal, and, most importantly, pathogenic process in AD.Overall the findings described in Lee et al.


Surgical boot camps are becoming increasingly popular in Otolaryngology–Head and Neck Surgery (OHNS) residency programs. Despite pioneering virtual reality and simulation-based surgical education, these boot camps have lacked critical appraisal. The objective of this article was to examine the adoption and utility of surgical boot camps in OHNS residency training programs around the world.Ovid Medline and PubMed databases were systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews. Additionally, a grey literature search was performed.Inclusion criteria were peer-reviewed publications and grey literature sources that reported on OHNS boot camps for the novice learner. The search was restricted to human studies published in English. Studies were excluded if they were not examining junior trainees.. Following removal of duplicates, screening, and full text review, 16 articles were included for analysis. Seven major boot camps were identified across various academic sites in the world. Most boot camps were one-day intensive camps incorporating a mixture of didactic, skill specific, and simulation sessions using an array of task trainers and high-fidelity simulators focusing on OHNS emergencies. Studies measuring trainee outcomes demonstrated improvement in trainee confidence, immediate knowledge, and skill acquisition.A total of 551 articles were identifiedSurgical boot camps appear to be an effective tool for short term knowledge and skill acquisition. Further studies should examine retention of skill and maintenance of confidence over longer intervals, as little is known about these lasting effects. Upon completing medical school, junior trainees enter post-graduate training programs with dramatically increased responsibilities. To address the concern regarding trainee skill inadequacy, surgical boot camps were developed to help develop skillsets from interpreting diagnostic imaging to performing surgical procedures .The educational design of most surgical boot camps is a combination of didactic learning and small group simulation sessions. Both governing medical educational bodies of Canada  and the United States  have embraced competency-based educational frameworks for post graduate medical education (PGME) . These fLiterature examining the role of surgical boot camps has been extensively covered over the past decade. The majority of studies have examined the following outcomes: knowledge and technical skills acquisition, team communication skill development, and individual confidence improvement –6. MoreoA scoping review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis scoping review (PRISMA-ScR) guidelines was performed in February 2021 . The resFour reviewers  independently screened all abstracts to identify studies that fulfilled the predetermined eligibility criteria. Any disagreement between the reviewers was resolved by consensus. Qualitative data from each included study was extracted using standardized data forms including the study’s title, author(s), year of publication, education themes, and outcomes assessed.A total of 21 articles were identified by Ovid Medline, 527 articles by PubMed, and 3 articles from a grey literature search. Following the removal of the duplicate records, 530 abstracts were screened , acute airway obstruction from angioedema (43%), and facial/neck trauma (29%). The most common task trainers were surgical airway (71%), epistaxis (57%), peritonsillar abscess drainage (43%), and bag mask ventilation with tracheal intubation (29%). High fidelity cadaveric and mannequin-based task trainers for task specific procedures appear to be the current trend. All studies that used high fidelity simulation scenarios used the Laerdal  SimMan® adult simulator. SimMan® offers a highly realistic training model with real time neurological and physiological function.Despite some of the diversity in task trainers and simulations used across the world, the principal theme in all boot camp curricula appeared to be management of emergency situations and on-call scenarios. The goal was to have junior trainees leave the camp equipped with the skillset to identify and triage acute emergencies, perform basic minor airway procedures, and communicate and activate emergency protocols. We noted that trainee participation in introductory boot camps appears to improve their confidence, immediate knowledge acquisition, and immediate improvement in procedural skills in comparison to traditional didactic methods of learning , 91, 93.Despite strongly positive outcomes from boot camps and simulation training, criticisms of the lack of evidence to suggest long-term retention exist , 67. ThrAlthough boot camps are typically delivered at the beginning of OHNS programs because they are introductory, consensus on when they should be offered is lacking. When surveying American OHNS program directors, a slight majority felt boot camps should be offered within the first few months of residency . InteresBoot camp style training programs for junior OHNS are becoming widely adopted across the world. Fuelled by the utilization of simulation technology to deliver time-effective education for common OHNS emergencies, these programs embrace the educational shift towards competency-based accreditation standards for residency programs. A number of studies have justified this form of education to improve trainee’s performance, confidence, and skill in the short term. However, current literature has failed to examine a number of important long-term outcomes. Future studies that examine the effect of OHNS boot camps on long term outcomes will play a critical role justifying widespread adoption of boot camps for resident education.


Without comprehensive accountability for citizen values, divergent stakeholder interests complicate rather than address problems. Second, the oral health community remains disconnected from the broader health community. Although oral diseases and noncommunicable diseases share common risk factors and sequelae, oral health systems rarely benefit from innovations in other areas of health care.Therefore, a complex systems problem exists, characterized by limited accountability for incorporating citizen values and research evidence on the effectiveness of oral health programmes and interventions at systems level; for seeking greater integration with broader health systems; and for identifying the critical junctures where path dependencies can be overcome. Inertia and inaction will leave us with a persistent, albeit largely preventable, burden of oral diseases. A different approach is needed to improve oral health systems. Evidence-informed deliberative processes provide one promising approach. Citizen panels can gather citizens with diverse backgrounds and experiences to collectively deliberate about key oral health-system problems, options to address them and key implementation considerations. The gathered citizen values can then be used in policy-making processes to counter narrow stakeholder interests that perpetuate a separation of oral health from the broader health system and that block efforts to improve governance, financial and delivery arrangements.Recent studies describe the role of citizen deliberations for context-specific health policy-making.,Deliberative processes can also be leveraged at the community level.On the clinical practice level, citizens with experience as patients can be involved in deliberations about quality improvement. Iterative reflective learning based on patient feedback can spur quality improvement.Lancet Commission on Oral Health and the World Dental Federation’s Vision 2030 reportIn the oral health context, however, take-up of deliberative approaches as outlined above is currently limited. To ensure access to essential oral health care for everyone without causing financial hardship, the oral health community needs to commit to harnessing citizen values via evidence-informed deliberative processes. Describing the problem without identifying actionable solutions and implementation strategies is no longer an option. Recent developments such as the WHA74.5 Resolution,


The outcome of first-episode psychosis (FEP) varies and may be predicted by several baseline measures. In the Helsinki Early Psychosis Study, young adults with FEP (n=97) from the Helsinki area in Finland were broadly assessed as soon as possible after first psychiatric contact for psychosis. Age- and gender-matched population controls were also assessed (n=62). The participants were followed up via appointments and medical records. We present both published and unpublished results on predictors of 12-month clinical, functional, and metabolic outcomes. More severe cognitive deficits at the beginning of treatment predicted several outcomes such as occupational status and functional level – beyond baseline positive and affective symptom levels, but not when negative symptoms were accounted for. More severe baseline obsessive-compulsive symptoms were predictive of a lower rate of remission, whereas a higher level of anxiety symptoms predicted better functional outcome, when the severity of positive symptoms was adjusted for. Adverse childhood experiences measuring cumulating psychosocial stress did not predict occupational status or functional level when positive and negative symptoms and neurocognition were controlled for, whereas in controls having experienced school bullying was associated with lower functioning. Insulin resistance in early psychosis appeared as an early marker of increased vulnerability to weight gain and abdominal obesity in young adults with FEP. Further, increased waist circumference predicted worsening low-grade inflammation, increasing further the cardiovascular risk. In sum, we have found different types of prognostic markers in FEP. Identifying the individuals at risk of less favorable outcomes could affect treatment choices in FEP.No significant relationships.


Lipid droplets (LDs) are spherical, single sheet phospholipid-bound organelles that store neutral lipids in all eukaryotes and some prokaryotes. Initially conceived as relatively inert depots for energy and lipid precursors, these highly dynamic structures play active roles in homeostatic functions beyond metabolism, such as proteostasis and protein turnover, innate immunity and defense. A major share of the knowledge behind this paradigm shift has been enabled by the use of systematic molecular profiling approaches, capable of revealing and describing these non-intuitive systems-level relationships. Here, we discuss these advances and some of the challenges they entail, and highlight standing questions in the field. Lipids constitute essential building blocks for cell membrane structures, powerful sources of energy through β-oxidation, and modulators of cell compartment transactions and cell signaling and behavior . Howeverlipid bodies; or adiposomes in early studies—constitute a safe and efficient means to store lipids, particularly for organisms exposed to environments with intermittent nutrient availability. They appeared early in evolution and can be found across all eukaryotic phyla studied, and in virtually all cell types of higher metazoans  are localized to the crowded surface of the LD, through mechanisms still undergoing characterization . Recent The particular ultrastructure of LDs, with a spherical core devoid of any molecules apart from triacylglycerides and cholesterol species, favored their long-standing view as relatively inert inclusions floating in the cytoplasm, passively subject to growth and consumption cycles . This viWhile relatively labile under routine immunolabeling procedures involving cell permeabilization with detergents, LDs are cell structures particularly amenable for imaging and extraction of rich multiparametric information . Their characteristic spherical morphology and the availability of highly specific cell/tissue permeable dyes for neutral lipids  facilitate automated segmentation routines and the computing of their number, size and relative position across extensive datasets  Figure . This kiBecause LD formation and function are significantly conserved across eukaryotic phyla , differeSaccharomyces cerevisiae is a first prominent example: the versatility and ease of use of this model unicellular eukaryote allows for the combinatorial interrogation of genetic interactions across the whole genome, using different readouts—from subcellular imaging to relative survival across different limiting growth conditions—; this allows for the precise mapping of genetic networks and enzyme complexes to as yet unparalleled resolution   ; or the o below) . Innovato below) , have alCaenorhabditis elegans is a multicellular model system whose use in research largely developed during the birth of molecular biology  to exert its function. Recent C. elegans screening studies have also provided insights onto the regulation of the formation of nuclear LDs (nLD); apart from COPI components and the seipin homolog SEIP-1, the authors identified the nuclear inner membrane NEMP-1/Nemp1/TMEM194A as a required gene for nLD formation  as an important regulator of lipid accumulation in adult flies .A recent genome-wide siRNA screen was performed for regulators of LD biogenesis in THP1 human macrophages . This stAn emerging subfield in cell biology is the study of interorganelle communication through specialized structures, commonly referred to as membrane contact sites (MCSs), which allow for the regulated interchange of molecules and information to achieve coordinated functioning . Studyinbona fide LD proteins are indeed specific substrates for ERAD E3 ligases (see below)  organizing LD distribution through their cooperation with the LD-ER linker seipin  . Systemae below) . Anotherr seipin . Interesr seipin , and ther seipin . All ther seipin ; its molWhile the close apposition of LDs to mitochondria and its link with fatty acid consumption had been early suggested , specifiPeroxisomes enable β-oxidation of very long chain fatty acids in metazoans, and participate of fatty acid catabolism to its completion in yeast or plants . Recent Contacts between LDs and subcompartments of the endosomal system have also been described , but theDrosophila ; this particular study demonstrated the recruitment of RNA binding proteins participating in viral RNA replication to LDs . Histones, which can be toxic for cells when mislocalized or secreted ; ERAD appears coordinated with lipid metabolism (particularly cholesterol biosynthesis) through the control of different enzymes  for each protein across different cell compartments, as located by specific bona fide markers. These correlative approaches have been rather successful on describing the proteomes of different cell compartments including LDs, especially in studies using machine-learning approaches to describe distribution changes across conditions  can be nditions .in vitro and in vivo; after subsequent affinity purification, mass spectrometry allows for the identification of labelled cell proteome subsets. A variety of applications have been also derived to inform of specific events such as posttranslational modification or interorganelle communication  nication . A relatm radius . Becausem radius . These msee previous section).Bersuker, Olzmann and collaborators fused the APEX2 ascorbate peroxidase  to inertThese studies have provided reference lists of ‘core’ LD proteins, extremely valuable to understand how responsive this subproteome is, what stimuli regulate their localization to LDs, and what molecular mechanisms underpin such localization . Surprisde novo biosynthesis and triacylglycerol conjugation, respectively)—and LD tethering to replication factories through the RAB18 GTPase and accessory proteins such as Annexin A3 (ANXA3) , induce LD formation and engage in complex interactions through their surrounding phagophore with these organelles, presumably to utilize their resources  also induce the formation of LDs in the host cell, can liberate lipases to obtain free lipids from host LDs, and actively uptake these free lipids for the completion of their biological cycle  . Other F (ANXA3) . Intraceesources . Eukaryoal cycle .However, this model of LDs as solely “comforting pantries” for intracellular invaders does not fit with different lines of evidence. First, formation of LDs is actively promoted in the cell by the activation of pathogen pattern recognition receptors (PRRs) by their microbial invader product , such as bacterial surface lipopolysaccharides (LPS) and glycolipids  or nucleUsing an experimental system where LD formation is induced in liver upon starvation and LPS administration in mice (thus minimizing effects from reduced food intake upon exposure to LPS), we applied multiplexed isobaric labeling and tandem mass spectrometry to profile the proteome of purified hepatic LDs, and its response to PRR activation . We obseLeveraging on variability across biological replicates, which can capture relevant biochemical relationships , hierarcListeria monocytogenes or herpes simplex virus type 1  is an amphiphilic peptide with prominent roles in innate defense against bacterial infection . Its preDrosophila antimicrobial defense upon recruitment by the Jabba protein  support these are general principles  Figure . Howeverbacteria . The ovebacteria  and conttb types .C. trachomatis-infected epithelial cells found changes associated with LD metabolic reprogramming (both increased lipid usage and anabolism), and identified PLIN2 as a perilipin protein specifically enriched upon infection , a report on the proteomic composition of LD-rich fractions purified from nfection . Of note helices ; studiesWhile cell-based high-content screenings on LD biology have been fruitful, recent developments of these technologies could allow for the systematic interrogation of how these structures are regulated in contexts closer to physiological conditions, and how they relate to many other tissue components and markers. Automated culture and high-content analyses of organoids that capture tissue microenvironment properties have been reported . Recent de novo phospholipid synthesis are important parameters determining the size and coalescence of LDs (4P) species accumulate in large LDs of cells depleted of the ORP5 regulator, which has been proposed to supply phosphatidylserine from PI4P  constitute a versatile means to modify the function, localization, stability, and interactions of proteome subsets in a coordinated manner. Protein phosphorylation comprises a large share of PTMs, driving signaling pathways for the transduction of different cues, including several modulating LD functions. An example is the regulation of LD growth and dynamics by different nodes of nutrient state sensing networks in the cell . FastingThe advancements brought by functional genomics and molecular profiling to all fields in cell biology are particularly prominent in LD research, as their characterization may have lagged as compared to other cell compartments, and some of their emerging functions  were particularly unexpected. Novel unbiased technologies will surely contribute to uncover new systems-level aspects of the roles of LDs in cell function and their emerging relationships with other cell structures, such as the nucleus and the secretory apparatus.


Demands of caregivers of persons living with dementia (PLWD) are often influenced by the context of their caregiving situation. This study examines factors associated with caregiving burden in terms of task time and task difficulty among paid and unpaid caregivers of PLWD. Cross-sectional baseline survey data were analyzed from 110 paid and unpaid caregivers of PLWD participating in a larger NIH-funded study assessing the feasibility of using a novel in-situ sensor system. Oberst Caregiving Burden Scale constructs of task time and task difficulty served as dependent variables. Two least squares regression models were fitted, controlling for contextual items related to the caregiver, care recipient, and caregiving logistics. Caregivers whose care recipients were female , had more chronic conditions , and had lower Mini-Mental State Exam scores  reported higher task time burdens. Caregivers whose care recipients had other paid caregivers  and spent more months/years caring for their care recipients  reported higher task time burdens. Caregivers’ task time burden was positively associated with their emotional stress level . Caregivers’ task difficulty burden was positively associated with their emotional stress  and depressive symptomatology . Results reinforce the relationship between caregiver burden and mental health. While the care recipient’s disease profile and needs were drivers of task time burden, which may also require coordination with other paid caregivers, task difficulty was emotionally driven. Findings highlight the importance of caregiver support services and programming for mental health.