Tropical rainforest disturbance and conversion are critical drivers of biodiversity loss. A key knowledge gap is understanding the impacts of habitat modification on mechanisms of community assembly, which are predicted to respond differently between taxa and across spatial scales. We use a null model approach to detect trait assembly of species at local- and landscape-scales, and then subdivide communities with different habitat associations and foraging guilds to investigate whether the detection of assembly mechanisms varies between groups. We focus on two indicator taxa, dung beetles and birds, across a disturbance gradient of primary rainforest, selectively logged rainforest, and oil palm plantations in Borneo, Southeast Asia. Random community assembly was predominant for dung beetles across habitats, whereas trait convergence, indicative of environmental filtering, occurred across the disturbance gradient for birds. Assembly patterns at the two spatial scales were similar. Subdividing for habitat association and foraging guild revealed patterns hidden when focusing on the overall community. Dung beetle forest specialists and habitat generalists showed opposing assembly mechanisms in primary forest, community assembly of habitat generalists for both taxa differed with disturbance intensity, and insectivorous birds strongly influenced overall community assembly relative to other guilds. Our study reveals the sensitivity of community assembly mechanisms to anthropogenic disturbance via a shift in the relative contribution of stochastic and deterministic processes. This highlights the need for greater understanding of how habitat modification alters species interactions and the importance of incorporating species’ traits within assessments.The online version contains supplementary material available at 10.1007/s00442-020-04829-z. Habitat modification via selective logging and forest conversion to agriculture is widespread across the tropics , and interactions with other species that are characteristic of anthropogenic disturbance . The majority of the concession (~ 90%) has been selectively logged, primarily between the 1970s and 2008 across two rotations of logging  logging concession in eastern Sabah, Malaysian Borneo  across all four habitats]. Each site consisted of one line transect for bird sampling and two-line transects (a minimum of 500 m apart) for dung beetle trapping (see below for further methods). Sampling for birds and dung beetles occurred at the same sites across the forested habitats and at three of the oil palm sites, however the fourth oil palm site, for each taxa, was sampled in different locations due to logistical reasons  (Online resource 1a). Sampling within oil palm was restricted to mature plantations (10–15 years old). The environmental conditions across sampling years remained similar . Primary forests are heterogeneous in structure with a dense canopy, extended vertical strata, and an open understorey with low densities of lianas when compared to logged forests . Sampling effort was equalised across habitat types for dung beetles and birds ; Online Resource 1c; following Edwards et al. Dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae) were sampled using standardised baited pitfall traps across all habitats [nMicrosites = 192 ; Online Resource 1c; following Edwards et al. Unlimited-radius point counts were used to sample birds across all habitats [Functional traits that reflect the key functional roles of dung beetles and birds were assessed for use with trait assembly null models described below. We combined both behavioural  and morphological (body size and bill structure) traits to capture a greater proportion of the variation across species as per Edwards et al.  to creatTo assess how functional traits and species abundances influence community assembly, we used a null model approach to test for trait divergence or convergence across our disturbance gradient  and landscape (n = 4) scale (Online resource 1), and tested whether SESRaoQ values were significantly different from zero (indicating a random trait distribution) using a student’s t-test.To then be able to assess community assembly patterns across our disturbance gradient we compared the deviation of observed RaoQ from the expected null distribution, using the standardised effect size (SES) (SES_RaoQ), taking the approach of Gottelli and McGabe . SESRaoQnMicrosites = 40 per habitat; birds: nMicrosites = 48 per habitat) and landscape (nSites = 4 per habitat) scales. Therefore, for any given subset of the community (see variations of community subsets below), four models were run for each taxa. All null model randomisations were run with 10,000 permutations and with abundance data, which has been shown to maximise detection power . This model has the effect of removing any relationship between the traits and abundances of species co-occurring at a sampling site while maintaining the sample species richness and the total sample abundance . Importantly, this maintains the link between species abundances and traits (thus differing from model 1), while also maintaining species frequencies and total abundances, but allowing sample abundance and richness to vary . Habitat specialists were defined as those species that were unique to either oil palm  or forested habitats  . We analysed both subsets of species using the same null models at both the local and landscape scales. To ensure our definition of habitat association was not influenced by rare species , we re-analysed these models with singletons removed. The results mirrored those from the full community; we, therefore, present only the full community results in the main text and provide both model outputs in the supplementary material (Online resource 5).To explore whether any changes in co-occurrence patterns related to changes in interactions determined by species’ habitat associations, we tested whether assembly mechanisms differed between those species shared across all habitats  and those that were not (non-shared). Habitat generalists were defined as those species found in all four habitats  described in the Elton Trait database, which are based on the summed proportion of five individual diet components for each species , at the local scale dung beetle communities varied considerably. Random trait assembly was found in primary and twice-logged forests, while trends in once-logged forest indicated trait convergence (t-test: P < 0.01) and in oil palm trait divergence (t-test: P < 0.01) , we found no evidence of non-random trait assembly for dung beetle communities at either spatial scales .Nesting guilds of dung beetles indicated uniform trait-based assembly across habitats for rollers, which displayed trait convergence at both scales using model 1. Insectivore communities indicated strong trait convergence across all habitats and scales .Dominant avian feeding guilds showed variation in trait-based assembly patterns using We explored the manner in which tropical land-use change influences species co-occurrence patterns to infer community assembly mechanisms in two indicator taxa. To our knowledge, this is the first assessment of dung beetle co-occurrence patterns, and the first multi-taxon, multi-spatial scale analysis of co-occurrence in relation to anthropogenic habitat change. In revealing evidence of non-random assembly at local scales in dung beetles, and variation between trait convergence and random assembly in birds across the disturbance gradient Fig. e–h, our Model 1, which can detect limiting similarity, varied across the disturbance gradient, whereas model 2, which reliably detects environmental filtering  and conversion . Critically, we highlight the potential hidden effects of land-use change beyond altered community structure Below is the link to the electronic supplementary material.


The successful implementation of antiretroviral therapy (ART) in women living with HIV (WLWH), either for their own health or for prevention of mother-to-child transmission (MTCT), has reduced MTCT risk of HIV to <5% . Yet, inIn addition to the risk of HIV infections that occur early in life via breastfeeding, sexual transmission during adolescence and adulthood also represents a significant and ongoing mode of infection . A pediaSeveral recent studies have indicated that the early life immune system may present some advantages for elicitation of HIV-specific antibody responses. The purpose of this review is to summarize these studies and highlight the unique ability of the early life developing immune system to mount robust and durable immune responses against HIV, compared to adults. Additionally, the potential of harnessing neonatal immune ontogeny to develop an effective earlylife HIV vaccine is emphasized.Owing to maturational differences in the early life and adult immune systems, the ability of infants to generate vaccine-specific immune responses has traditionally been considered as impaired [reviewed in ]. AdditiNeonatal nonhuman primate (NHP) studies have provided encouraging results regarding the ability of infants to mount durable immune responses against HIV or simian immunodeficiency virus (SIV) vaccines –19. In fTo date, only a few pediatric HIV vaccine trials have been completed . While nAlthough the induction of cross-clade bNab is 1 of the major goals of any HIV vaccination strategy ,37, so fWhile elicitation of bNabs remains a priority of HIV vaccine development, a combination of neutralizing and non-neutralizing effector responses might be crucial for an efficacious vaccine. A recent study has indicated that polyfunctional antibody responses are predictive of bNab development , suggestNewborns transition from a relatively sheltered intrauterine environment to an environment with multiple antigenic exposures. To obtain survival benefits during the period of immune maturation, newborns establish a highly tolerogenic environment and exhibit a distinct immune profile than adults [reviewed in ]. TherefWhile alum has been the standard adjuvant of choice for commercial pediatric vaccines, HlV pediatric vaccine trials have reported the superiority of MF-59 adjuvant in mounting potent and durable antibody responses when compared to alum. In PACTG 230 trial, the MF-59-adjuvanted vaccine formulation was associated with durable anti-Env IgG responses, which was associated with higher breadth and durability as compared to the alum-adjuvanted counterpart . This inEmerging evidence suggests that an individual’s microbiome can influence immune responses to vaccination . TherefoNeonates and infants possess unique immunological characteristics that promote the development of protective immunity via immunological and molecular pathways distinct from those of adults. Therefore, a deeper understanding of the infant immune system is needed to develop novel HIV immunization regimens tailored to the infant’s immune landscape. The fact that the most recent adult HIV vaccine trial HVTN 702), done in South Africa, which tested a canarypox vector-based vaccine (ALVAC-HIV) with HIV subtype C gp120 protein adjuvanted with MF-59, was recently discontinued due to lack of efficacy  highligh2, done iThe pediatric HIV vaccine protocol HVTN 135 is currently in development to assess the safety and immunogenicity of HIV CH505 transmitted-founder (T/F) gp120 adjuvanted with the TLR4 agonist GLA-SE in HIV-exposed infants. This Phase I trial will use the CH505 T/F protein that is currently being tested in an adult HIV vaccine trial, and the results from HVTN135 will determine if this vaccine is safe to be used in infants. Additionally, this trial will indicate whether infants develop a distinct immune response to this vaccine as compared to adults, hence providing valuable information for the design of future pediatric HIV vaccine trials. Ultimately, additional clinical trials will be required to assess if immunization at birth can protect infants from vertical HIV transmission during infancy and against sexual HIV transmission during adolescence.


Using a stress process framework model, this study is the first to comprehensively examine the role that religious/spiritual struggles play in the lives of informal dementia caregivers. A convenience sample of 156 informal dementia caregivers completed a scale measuring six domains of religious/spiritual struggles, as well as other measures of primary stressors, background/contextual variables, and mental health outcome (depression). Overall levels of religious/spiritual struggle were low, but 26 percent of the sample were classified as possible cases of clinically significant religious/spiritual struggle for at least one of the six domains. Of this group, 49 percent acknowledged struggles with ultimate meaning. Religious/spiritual struggles predicted greater self-reported depression over and above number of care recipient problem behaviors (primary stressor), caregiver sex, and caregiver personality . Although no individual domain of religious/spiritual struggle emerged as most salient, caregivers reported significantly more ultimate meaning struggles than demonic or interpersonal struggles. These findings support the growing body of research suggesting that religious/spiritual struggles serve as a secondary stressor, adding predictive power to background/contextual factors and to primary stressors for informal dementia caregiver mental health outcomes. Further research in this area may advance efforts to better equip both secular and religious professionals to provide evidence-based counsel to informal dementia caregivers.


Excellent pulmonary function is one of the strongest predictors of longevity across animal models and human populations. Unfortunately, none of the major age-associated pulmonary diseases – obstructive lung disease, pulmonary fibrosis, and increased susceptibility to pneumonia – have strongly effective disease modifying therapies. There is growing evidence that normal age-associated decline in pulmonary function and major age-associated pulmonary diseases are linked to the hallmarks of aging including senescence, nutrient signaling dysregulation, mitochondrial dysfunction, and telomere disorders. This presents opportunities for collaboration between gerontologists and pulmonologists to unravel age-associated developmental mechanisms and design novel treatments. In this symposium, leaders in pulmonary aging research will present novel data on links between aging and pulmonary health and geroscience-based interventions under study. Dr. Sanders will provide an overview of the scientific and clinical space and present epidemiologic associations between aging biomarkers, early pulmonary fibrosis, and mortality. Dr. Le Saux will discuss senescence and specifically how eicosanoid biology may explain organ-specific patterns of senescence-associated fibrosis. Dr. Thannickal will discuss age-associated perturbations in metabolism and mitochondrial function and targeting these pathways to improve lung function and treat pulmonary diseases. Dr. Newton will discuss mechanisms and clinical applications of telomere biology to pulmonary aging. Symposium attendees will (1) be poised to generate collaborations between gerontologists and pulmonologists to address existing knowledge gaps in mechanisms of pulmonary aging, and (2) develop a better understanding of translational opportunities to design geroscience-based diagnostics and therapeutics to improve pulmonary health with aging.


Ovarian cancer, cervical cancer and endometrial cancer are three relatively common malignant cancers of the female reproductive system. Despite improvements in female genital tract cancer detection and development of new therapeutic approaches, there are still poor prognoses and some do not respond to therapeutic patterns, displaying low survival and high frequency of recurrence. In an era of personalized medicine, novel therapeutic approaches with greater efficacy for these cancers represent an unmet need. One of the actionable signaling pathways is the fibroblast growth factor receptor (FGFR) signaling pathway. Several mutations and alterations in FGF/FGFR family members have been reported in human cancers. FGF/FGFR signaling pathway has become a new target for cancer therapy. This review will summarize the role of FGFR pathway and the genetic alterations of the FGF/FGFR related to female reproductive system cancer. We will describe the available inhibitors of FGFR pathway for potential treatment of female reproductive system cancer. Furthermore, we will discuss FGFR-targeted therapies under clinical development for treatment of female reproductive system cancer. Endometrial cancer, ovarian cancer and cervical cancers are three relatively common malignant tumors of the female reproductive system. Endometrial cancer that accounts for more than 95% of cases of uterine cancer is one of the most prevalent forms of gynecological cancers. It is thought to be caused by increasing estrogen levels relative to progesterone in the body. Endometrial cancer at stages I and II responds well to surgical interventions, but the disease at stages III and IV has poor prognosis with low survival rates. Ovarian cancer is the third leading gynecological malignancy worldwide and carries the highest mortality. Most ovarian cancers initiated from epithelial cells and are thus composed of poorly differentiated epithelial cells in vitro and in vivo tumor models harboring FGFR aberrations, an increasing number of researchers have selected FGFRs as targets for anticancer drug development Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinase (RTKs) encoded by four different genes FGFR1-4), among them, FGFR1-FGFR3 generate two major splice variants of immunoglobulin-like domain III, referred to as IIIb and IIIc, which are essential determinants of ligand-binding specificity , among tSome of the most striking clinical findings regarding FGFRs relate to how these receptors are implicated in female genital tract cancers. In this article, we describe recent advances of FGFR signaling pathway in endometrial, ovarian and cervical carcinogenesis and progression. Moreover, we highlight the genetic variations (including somatic mutation and gene amplification) of FGF or FGFR family members and summarize the FGFR-targeted therapies under clinical development for treatment female genital tract cancers.FGFRs in response to fibroblast growth factors (FGFs) transmit signals. The FGF family belongs to a large family of growth factors with significant expression profiles in the female reproductive tract and potentially important roles on fertility. This family is composed of 18 secreted proteins that are grouped into 5 subfamilies according to sequence homology Figure 1).Notably, dysregulation of the FGFR pathway is associated with various human cancers and is considered as an oncogenic signaling pathway FGF/FGFR signaling governs fundamental cellular processes such as cell survival, proliferation, migration, differentiation, embryonic development, organogenesis, tissue repair/regeneration, and metabolism Figure 2). Recent study suggested that the fibroblast FGF/FGFR family could interact with PI3K/AKT pathway and subsequently involve in the carcinogenesis of ovarian cancer. In endometrial cancer cell lines, loss of PTEN has been suggested as apotential mechanism of resistance to FGFR inhibition Genetic variations, especially SNPs, and genomic alterations, such as gene amplification, chromosomal translocation, and point mutation, are involved in the transcriptional upregulation of FGFR mRNAs and the functional activation of FGFR proteins during carcinogenesis . The main challenges have included (i) determining optimal diagnostic procedures for FGFR molecular alterations, and standardizing the definition of FGFRs amplification; (ii) detecting rare-frequency fusion genes involving various partners; (iii) discriminating between passenger and driver alterations; (iv) integrating the available information within a specific cellular and tumor heterogeneity context.In clinical, although anti-FGFR therapy represents a promising targeted cancer treatment, early phase clinical trials have had mixed success, with response to therapy dependent on several factors, including cancer type, tumor histology, and presence or absence of certain biomarkers Cervical cancer is the fourth most common female malignancy worldwide. Each year, more than half a million women are diagnosed with cervical cancer and the disease results in over 300,000 deaths worldwide et al. The oncogenic significance role of the FGFRs has been elucidated in cervical cancer. Choi et al. Ovarian cancer is the leading cause of death from gynecologic cancers in vitro and in vivo have shown that silencing FGFR4 and inhibiting ligand-receptor binding significantly decreased the proliferation, survival, and invasiveness and increased apoptosis of ovarian cancer cells, suggesting that FGFR4 protein expression is a new therapeutic modality for this disease and will improve its survival in clinical trials FGFR4 is a prognostic marker for advanced-stage, high-grade serous ovarian cancer. Experiments In vivo experiment has shown that FGFR inhibitor decreased the growth of FGFR2-mutated endometrial cancer xenograft models Endometrial cancer is the most common gynecologic malignancy among women in developed countries, with an estimated 63,230 new cases in 2018  et al. Table The FGF/FGFR signaling pathway is frequently deregulated in human cancers. Over the last years, several mutations and alterations in FGF-FGFR pathway have been reported in cancer et al. et al. Previous studies of germline FGFR mutations indicate that point mutations can result in differential localization and signaling et al. Besides FGFR aberrations, a number of studies have also shown that genetic variations of FGF are associated with the disease. Take FGF2 for example, our group previously found that the polymorphisms of FGF2 gene are significantly associated with obesity and osteoporosis in Chinese population Since FGF/FGFR signaling plays a crucial role in cancers, a variety of small molecule FGFR inhibitors target FGF/FGFR signaling pathway have been developed and shown significant therapeutic effects in pre-clinical and clinical studies Actually, the most clinically advanced compounds are non-selective TKIs, such as brivanib, dovitinib, lenvatinib, ponatinib, nintedanib, and cediranib. Most of these inhibitors target ATP binding pocket in the TK domains of FGFRs through reversible or covalent bonds To date, the most clinically advanced FGFR TKIs in FGFR targeted treatment is dovitinib (TKI258), which is now being tested in endometrial cancer patients with FGFR2 mutation (NCT01379534). Brivanibis another dual TKI against FGFRs and VEGFRs, which was found to be effective in metastatic solid malignancies resistant to standard therapy and is currently being developed as an anti-angiogenic agent in Phase II clinical trials AL3818 (anlotinib) is a receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors , stem cell factor receptor (C-kit), platelet-derived growth factor (PDGFA), and fibroblast growth factor receptors . This study evaluates the efficacy of AL3818 studying tumor regression in endometrial cancer model Table 2).Several other TKIs are also summarized in Table in vitro and in vivo models of endometrial cancer characterized by FGFR activation due to genetic alteration Table 3). Phase II trials with genomic enrichment are ongoing. A number of clinical trials use AZD4547 in cancer. One recent finding revealed that combined treatment of BGJ398 and rapamycin may be a promising therapeutic strategy in the treatment of patients with ovarian cancer AZD4547 is a famous selective TKI that specific target for FGFRs (FGFR1-3) Table 3). Pre-clinical cancer models with genetic aberrations in the FGFR pathway, including FGFR2-mutated endometrial cancer, are particularly sensitive to FP-1039 mediated tumor inhibition Anti-FGFR mAbs as well as small molecules acting as traps for the ligands of the FGFR family might represent a new strategy for the treatment of tumors. Based on the identification and characterization of FGF ligands, FGF ligand traps have allowed the development of promising FGF-targeting molecules with potential implications for the therapy of FGF-driven tumors Figure A large effort to develop FGF/FGFR inhibitors as anticancer treatments is underway. The most clinically advanced anti-FGFR drugs are small-molecule TKIs, some of them are monoclonal anti-FGFR antibodies and FGF-trapping molecules. Those anti-FGFR drugs that have entered the clinical phases of development are summarized in The cancers of the female genital tract represent a leading cause of morbidity and mortality among women worldwide. Undoubtedly, in the past decade, FGF/FGFR signaling therapies are under development for the treatment of gynecologic malignancies as well as in many other solid tumors. Therefore, dissecting canonical FGF/FGFR signaling pathways is still valuable. Deregulation of the FGF/FGFR signaling axis is observed in a wide variety of human cancers In conclusion, targeting FGFR is a promising strategy in the treatment of female reproductive system cancer. It is plausible to hope that in the following years the research efforts in pre-clinical and clinical fields allow to establish an optimal treatment strategy in FGFR-addicted female reproductive system cancer population.


Preparedness of residents in long-term care (LTC) in the face of hurricane emergencies is a contested and largely unanswered question. Our prior work involving the U.S. Gulf Coast hurricanes of 2005-08 showed that exposure to various storms on nursing home (NH) residents resulted in significantly more deaths than reported by health care officials. This work also highlighted that evacuation of NH residents, compared to sheltering in place, was independently associated with morbidity and mortality. Hurricane Irma struck Florida on Sept. 10, 2017, prompting the evacuation of thousands of NH and assisted living community (ALC) residents. This symposium will discuss the effects of Hurricane Irma on vulnerable older adults residing in NHs and ALCs using mixed quantitative and qualitative methodologies. The first presentation will discuss morbidity and mortality of NH residents exposed to Hurricane Irma and will stratify by long stay/short stay status and hospice enrollment. The second presentation will discuss improvements and continued barriers to NH preparedness based on interviews with 30 administrators following Hurricane Irma. Using a novel methodology to identify residents of ALCs using secondary data sources, the third presentation will document AL resident morbidity and mortality risk following Hurricane Irma. The final presentation will highlight results of interviews with 70 stakeholders from small and large ALCs concerning the hurricane experiences of residents, including those with dementia. This symposium offers a multi-faceted view of a disaster’s effects on LTC residents across Florida, including novel data from the NH environment and lesser-examined ALCs.


Background: Preterm infants with hemodynamically significant patent ductus arteriosus (HsPDA) are exposed to low cerebral tissue oxygen saturation (rScO2) values. Additionally, infants requiring surgical ligation are at risk of further changes in cerebral oxygenation and postligation cardiac syndrome (PLCS). Previous studies have assessed the effect of PDA ligation on rScO2 with variable results.Cases description: In this report we analyse near-infrared spectroscopy (NIRS) and echocardiographic findings of two patients who underwent ligation of PDA and presented low cardiac output. Literature on regional tissue oxygenation saturation (rSO2) before and after PDA ligation was briefly reviewed.Discussion: Cerebral oxygenation values before and after PDA ligation may be influenced by gestational age, vasopressor use, ductal shunt volume, time of exposure HsPDA, chronological age and the presence of cerebral autoregulation. PLCS complicates 28–45% of all PDA ligations and is associated with higher mortality. Cerebral and somatic NIRS monitoring in the postoperative period may enhance the identification of PLCS at early stages.Conclusion: Cerebral oxygenation in the perioperative period of PDA ligation may be influenced by numerous clinical factors. Early detection of PLCS using multisite NIRS after ligation could prevent further alterations in cerebral hemodynamics and improve outcomes. A decrease in somatic-cerebral difference and/or a significant drop in somatic NIRS values may precede clinical signs of hypoperfusion. NIRS values should be interpreted as trends along with echocardiographic findings to guide goal directed interventions. After PDA ligation, a significant reduction (>20%) in rSrO2 and somatic-cerebral difference concurred with low LVCO in both cases in the absence of hypotension, oliguria and/or delayed capillary refill. In case 1, cerebral oxygenation decreased significantly at the end of measurement period compared to preligation baseline values (60 vs. 80%). In case 2, rScO2 remained unvaried.In the aforementioned cases, rSrOEarly detection of PLCS using multisite NIRS after ligation could prevent further alterations in cerebral hemodynamics and improve outcomes. A decrease in somatic-cerebral difference and/or a significant drop in somatic NIRS values may precede clinical signs of hypoperfusion. Further studies are needed to investigate the applicability of somatic-cerebral difference in preterm infants. Our report has many weaknesses. Firstly, we describe only two cases and no conclusions can be drawn regarding our findings. Secondly, somatic-cerebral difference although physiologically founded, has not been used in preterm infants. We consider that continuous and long lasting NIRS recording is a strength of this report, as well as the review of literature on NIRS findings before and after treatment.A prospective cohort study is recommended to evaluate the utility of two-site NIRS monitoring in the detection of PLCS. NIRS values should be interpreted as trends along with echocardiographic findings to guide goal directed interventions.Written informed consent was obtained from parents of both patient for the publication of any potentially identifiable images or data included in this article.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Diurnal cortisol slopes are stress-sensitive HPA-axis biomarkers implicated in cardiometabolic health outcomes and disparities. This study used two longitudinal cohort studies (CREATE and TRIAD) with harmonized variables to comprehensively examine what types of exposure to stressors are most salient for cortisol dysregulation in later life, and whether the characteristics of stressor exposure accounts for Black-White disparities in cortisol dysregulation . Black participants reported greater stressor exposure than Whites along some dimensions  but comparable exposure in others . Stressor exposure measures that captured psychological components  and pervasiveness  were more closely related to cortisol dysregulation than more objective measures . Everyday discrimination was associated with racial disparities.


This study aimed to identify accelerometer measured daily physical activity patterns and to examine how they associate with health-related physical fitness among 258 participants  from the Finnish Retirement and Aging Study. Wrist-worn ActiGraph accelerometer was used and health-related physical fitness measures included body composition, cardiorespiratory fitness and muscular fitness. Based on latent class trajectory analysis, six different patterns of daily physical activity was identified on workdays and two on days off. Having low activity throughout the workday was associated with poorest health-related physical fitness, whereas a combination of low or moderate activity during working hours and increase of activity level in the evening was associated with most favorable body composition and better physical fitness compared to the other trajectories. In conclusion, a large variation in the workday physical activity patterns and health-related physical fitness was observed among aging workers.


Opioid overdose risk is particularly high in immigrant communities partly due to limited English proficiency . Previous studies reported that social determinants of health (SDH) have been associated with risk for opioid overdose . The current study examines the association between SDH and literacy of opioid overdose risk among the immigrant population living in a rural area. Specifically, we examine the association in various age groups including young adults (aged 20 to 34), middle-aged (aged 35 to 49), and older adults (ages 50 to 75). Data were drawn from a sample of Korean American immigrants residing in rural Alabama (N=225). The participants administered the Brief Opioid Knowledge (BOOK) Questionnaire . Multiple regression analyses were conducted for three age groups to identify predictors of opioid literacy. Overall, older adults had lower levels of opioid literacy relative to their younger counterparts. Among young adults, low English proficiency, more chronic conditions, and greater depressive symptoms were significant predictors of limited opioid literacy. For the middle-aged adults, lower levels of health literacy and more pain symptoms were associated with limited opioid literacy. Among older adults, women, those with higher English proficiency, and lower health literacy had lower levels of opioid literacy. The findings demonstrated a greater vulnerability of older immigrants to limited opioid literacy. Different predictors based on SDH of limited opioid literacy across age groups have implications for tailored health promotion strategies to reduce opioid overdose risk.


Background: Surgical root canal retreatment is required when peri-radicular pathosis associated with endodontically treated teeth cannot be treated by non-surgical root canal therapy (retreatment), or when retreatment was ineffective, not feasible or contraindicated. Endodontic failures maybe happen when irritants remain within the confines of the root canal, or when an extra-radicular infection cannot be eradicated by orthograde root canal treatment. Following enhanced microsurgical techniques in the last years, the success rates of surgical root canal retreatment have improved considerably.Objective: The aim of this systematic review is to gather updated data in regard to the surgical root canal (retrograde) retreatment to heal the periapical lesions.Materials and methods: The electronic databases PubMed and Google Scholar were searched in this review using specific inclusion and exclusion criteria. The search was performed in June 2019 and updated in November 2019. Among 3900 studies, 10 studies satisfied the eligibility criteria and were included in the review to be analyzed.Results: The 10 studies showed the importance of surgical root canal retreatment as a treatment option in removing infections within the root canal system and its efficiency in periapical tissue healing. These studies investigated different aspects of healing of periapical lesion after surgical (retrograde) retreatment including success rates, follow-up duration, and updated studies in surgical (retrograde) retreatment.Conclusions: Surgical root canal (retrograde) retreatment demonstrates its efficiency in reducing the period needed for healing of the periapical lesions in short-term follow-up compared to conventional orthograde retreatment. Periapical lesions are one of the common pathological conditions affecting periradicular tissues . The micThe preliminary purpose of all endodontic procedures, especially cleaning and shaping, is to eliminate necrotic tissue and infective bacteria . Large pThere are several studies that were conducted to discuss the healing of periapical lesion after nonsurgical (orthograde) retreatment or surgical root canal treatment. However, few studies have investigated the healing of periapical lesion after surgical (retrograde) retreatment. Consequently, the aim of this review was to collect all updated and available studies including imperative information concerning the surgical root canal (retrograde) retreatment to heal periapical lesions.Material and methodsThis review has been compiled according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.Research QuestionThe following was the research question for the systematic review: “The best endodontic treatment option for the healing of periapical lesions: is it surgical retrograde retreatment or conventional orthograde retreatment?”.Literature SearchWith respect to the question of the study, we searched the literature and identified relevant studies. The literature search was formulated in June 2019 and then updated in November 2019. A web search was done through PubMed (2009-2019) and Google Scholar (2009-2019) with MesH terms and/or in various combinations .Relevant articles had been read and assessed by the introduction of the close meaning ideas by the study reviewers. Full articles were obtained for most of the titles and abstracts that met the inclusion criteria, the full text was accessed. From each included article, study design, interventions, and findings were extracted. Articles used were categorized into two main groups (free and restricted). Free ones have been downloaded directly by the URLs generated from the database. The restricted group has been downloaded by the institutional access of the King Abdulaziz University (KAU) library. Even though some articles did not match the main idea, they have been reviewed again & decided to be either relevant or irrelevant.Inclusion Criteria1. Native research released in the English language.2. Time framed articles released within 10 years (2009 - 2019).3. Studies carried out on human subjects only.Exclusion Criteria1. Articles that described healing of periapical lesion with management techniques excluding the surgical root canal retreatment.2. Articles that discussed healing of periapical lesion after surgical root canal retreatment by percentages and samples taken from animals.3. Review articles.Critical AppraisalEligible studies were independently analyzed by all reviewers according to the eligibility criteria as well as PRISMA guidelines. Any disagreement between the reviewers was resolved using discussion.Data Extraction and PresentationThe search strategy using the keywords and MeSH of the databases like PUBMED and Google Scholar yielded a total of 3,900 studies, of which 3,580 were either unrelated or duplicate topics. Among the potential 140 studies, the eligibility criteria were applied and ten studies were included in this systematic review. The summary of the search flow chart for this systematic review has been depicted in  retreatment including success rates, follow-up duration, and updated studies in surgical root canal (retrograde) retreatment. The studies included in this systematic review were one randomized controlled trial study, two prospective studies, one retrospective study, and six case reports -19,20-25DiscussionThe systematic review presents a comprehensive compilation of evidence taken from ten articles which included original studies. The sample size was up to 376 subjects seeking endodontic retreatment by the use of surgical retrograde retreatment. All included studies confirmed faster treatment time by surgical root canal (retrograde) retreatment Table . The recAlso, Del Fabbro et al. in 2007 and Torabinejad et al. in 2009 have compared the success rates of non-surgical orthograde and surgical retrograde endodontic retreatment ,28. TheySurgical root canal (retrograde) retreatment is defined as an important invasive procedure that permits fast treatment options minus the necessity of the extensive traditional method. Surgical retrograde retreatment demonstrates its efficiency in reducing the period needed for healing of the periapical lesions and suggests benefits that will result in better recognition among patients seeking faster results in short-term follow-up, but on the long-term follow-up showed not significant difference for healing of periapical lesions compared to conventional orthograde retreatment. However, more clinical trials are encouraged to inspect the results of surgical retrograde retreatment on the healing of periapical lesions.


The Long Life Family Study (LLFS) has longitudinally measured key aging phenotypes on 4,953 participants (539 pedigrees) in the USA and Denmark selected for exceptional familial longevity. On average, both generations of the LLFS sample are healthier than average for their age/sex, for many phenotypes. However, the pedigrees are heterogeneous, with different families showing familial clustering of protection for different phenotypes. Linkage analyses identified extremely strong genetic linkage peaks for many cross-sectional as well as longitudinal trajectory rates of change phenotypes. These peaks are NOT explained by GWAS SNPs (either measured or imputed). Pedigree specific HLODs and preliminary deep sequencing suggests that these peaks are driven by rare, protective variants running in selected pedigrees. Whole Genome Sequencing, a third longitudinal visit, and extensive OMICs  will help us resolve the mechanisms behind these protective genetically linked variants, and could illuminate new biology and enable new therapeutics.


The amygdala is a central hub for fear learning assessed by Pavlovian fear conditioning. Indeed, the prevailing hypothesis that learning and memory are mediated by changes in synaptic strength was shown most convincingly at thalamic and cortical afferents to the lateral amygdala. The neurotrophin brain-derived neurotrophic factor (BDNF) is known to regulate synaptic plasticity and memory formation in many areas of the mammalian brain including the amygdala, where BDNF signalling via tropomyosin-related kinase B (TrkB) receptors is prominently involved in fear learning. This review updates the current understanding of BDNF/TrkB signalling in the amygdala related to fear learning and extinction. In addition, actions of proBDNF/p75NTR and NGF/TrkA as well as NT-3/TrkC signalling in the amygdala are introduced. The amygdala is a telencephalic group of diverse, interconnected nuclei in the brain  receptors preferentially activated by NGF (nerve growth factor), TrkB receptors activated by BDNF as well as NT-4/5 (neurotrophin-4/5) and TrkC receptors by NT-3 (neurotrophin-3) Barbacid .While many findings regarding BDNF/TrkB signalling in cellular aspects of learning were initially reported for hippocampal and cortical circuits, BDNF/TrkB pathways in the amygdala emerged soon thereafter to be prominently involved in fear learning (see below). TrkB receptor as well as BDNF mRNA and protein were detected at moderate to high levels in various amygdala subnuclei , the posterior intralaminar nucleus (PIN) and the suprageniculate nucleus (SG)  or Y515 (Shc) phosphorylation site of the TrkB receptor, respectively , which drives the expression of Met-BDNF and leads to decreased activity-dependent BDNF secretion  were unaffected or impaired when assessed by skin conductance response or fear-potentiated startle, respectively  from tones not paired with the aversive US (CS−) in a discriminative fear learning task  (Meis et al. Interestingly, chronic BDNF reduction to about 50% of wild-type levels in BDNFThe LA is highly interconnected with the BA (Pitkanen et al. ARα1 subunits in amygdala cell cultures, which was supposed to elicit a transient hyper-excitability in the amygdala, thereby contributing to cellular mechanisms of memory consolidation (Mou et al. +/− mice displayed neither impaired basal synaptic GABAergic transmission nor altered inhibitory synaptic plasticity in the LA. However, positive modulation of interneuron activity by noradrenaline was significantly decreased by chronic BDNF reduction (Meis et al. Beside glutamatergic synaptic transmission, BDNF/TrkB signalling also regulates GABAergic neurotransmission (Gottmann et al. Beside the basolateral amygdala, the central nucleus is now considered as an important site of associative plasticity involved in fear memory (Ehrlich et al. In conclusion, BDNF/TrkB signalling increases excitatory synaptic transmission in different subnuclei of the amygdala and enables LTP. At GABAergic synapses, acute BDNF/TrkB signalling may lead to reduced inhibition and elevated excitability necessary for memory formation, while chronic BDNF reduction results in impaired interaction of GABAergic synaptic transmission with modulatory transmitters like noradrenaline and serotonin.After fear learning, repeated exposure to the conditioned stimulus alone leads to diminished fear responses (Myers and Davis +/− mice display an age-dependent deficit in extinction learning (Psotta et al. Val/Met or BDNFMet/Met mice as well as human Met allele carriers were impaired in extinguishing a conditioned fear response, associated with abnormal fronto-amygdala activity in humans (Soliman et al. +/− mice but was mimicked by overexpression of BDNF in the BLA from the end of extinction training onward (Karpova et al. A critical contribution of BDNF signalling in extinction was recently demonstrated. BDNFNeurotrophins are at first synthesized as precursor proteins, which are processed to the mature form by proteolytic cleavage (Lessmann and Brigadski Conflicting results are available about the distribution of TrkA receptors in the amygdala. While initially neither TrkA receptor mRNA nor immunoreactive cells for TrkA receptors were detected (Gibbs and Pfaff While neither NT-3 mRNA nor immunoreactive neurons were found in the amygdala (Phillips et al. Accumulating evidence indicates that BDNF/TrkB signalling in the amygdala plays a pivotal role in fear learning and memory as well as fear extinction. In the amygdala circuitry, BDNF/TrkB signalling contributes significantly to synaptic plasticity, which is widely accepted as a cellular mechanism underlying fear memory learning. In addition, downstream molecular signalling pathways triggered by TrkB activation are well documented. However, actions of BDNF/TrkB signalling in amygdala synaptic processes involved in fear extinction learning are far less understood. While behavioural studies suggest a significant contribution of BDNF signalling within the amygdala in extinction learning, analysis of the underlying cellular mechanisms warrants further studies.


Filial caregivers  are a part of the growing number of family caregivers in midlife and late adulthood. The responsibilities that filial caregivers navigate in midlife and late adulthood may expose them to multiple types of discrimination that may decrease their physical health, though this relationship has been understudied. As numbers of family caregivers grow, it is important to examine the potential vulnerability of younger and older filial caregivers’ physical health in the context of discrimination. Informed by the life course perspective, this study compares the physical health of younger (aged 34-64) and older (aged 64-74) filial caregivers who experience discrimination. Filial caregivers  from the Midlife in the United States (MIDUS-II) Survey reported on demographics, family caregiving, daily discrimination, self-rated physical health, and chronic conditions via questionnaires and phone interviews. Regression analyses showed no differences between younger and older adults’ self-rated physical health or average chronic conditions. However, moderation analyses revealed that younger filial caregivers who experienced greater discrimination reported poorer self-rated physical health than their older counter parts as well as younger and older filial caregivers who experienced less discrimination. Additionally, younger caregivers with greater discrimination exposure exhibited more number of chronic conditions as compared to other caregivers. The study results highlight the impact of the intersection between filial caregivers’ age and discrimination on physical health. Findings have the potential to inform programs that could promote the health of filial caregivers in the face of discrimination.


Although nonalcoholic fatty liver disease (NAFLD) is more prevalent in older individuals, the underlying mechanisms by which aging processes accelerate NAFLD are not fully understood. NAFLD can progress to nonalcoholic steatohepatitis (NASH), which in turn can lead to the development of cirrhotic liver disease and hepatocellular carcinoma (HCC). Since NAFLD, NASH, and HCC are rapidly increasing in the aging population, understanding the mechanism of how NAFLD progresses to NASH is crucial. NASH is emerging as the leading cause of chronic liver disease and the most rapidly growing indication for liver transplantation worldwide, with liver fibrosis being the most important predictor of liver failure in NASH . HoweverCRMertk) mouse model, the authors further showed that all-trans retinoic acid (ATRA)–induced ADAM metallopeptidase domain 17 (ADAM17)–mediated MerTK cleavage decreased the levels of MerTK receptor on macrophages and suppressed NASH fibrosis. ATRA is a major active metabolite of retinol stored in quiescent HSCs in healthy liver. In damaged liver, as HSCs are activated, they release retinol. Livers of subjects with NASH show lower levels of retinol than livers of subjects with simple steatosis [in vivo. However, given that MerTK is critical for maintaining tissue homeostasis in other settings, including atherosclerosis and myocardial infarction [Liver fibrosis is driven by the activation of hepatic stellate cells (HSCs) that produce collagen and other types of extracellular matrix. It has been widely reported that liver macrophages, including resident Kupffer cells and infiltrated monocyte-derived macrophages, can activate HSCs through releasing growth factors including TGFβ and PDGF . Howeverteatosis . Consistfarction , global In summary, Cai et al. uncover a previously unrecognized function of macrophage MerTK in NASH fibrosis and provide constructive insight on the potential therapeutic targeting of MerTK. However, this study opens up new questions worth exploring. Since MerTK is often seen as a protective regulator for tissue homeostasis, why doesn’t MerTK signaling trigger beneficial effects, including efferocytosis, dampening of inflammation, and resolution of inflammation in the context of NASH? Moreover, some studies have shown that Kupffer cells are protective in non-NASH liver injury models. However, Kupffer MerTK is detrimental in NASH. Does MerTK express in a unique subset of Kupffer cells that promote NASH progression? Finally, what are the mechanisms of decreased liver ATRA and increased GAS6 during NASH?


Coastal wetlands provide many critical ecosystem services including carbon storage. Soil organic carbon (SOC) is the most important component of carbon stock in coastal salt marshes. However, there are large uncertainties when estimating SOC stock in coastal salt marshes at large spatial scales. So far, information on the spatial heterogeneity of SOC distribution and determinants remains limited. Moreover, the role of complex ecological interactions in shaping SOC distribution is poorly understood. Here, we report detailed field surveys on plant, soil and crab burrowing activities in two inter-tidal salt marsh sites with similar habitat conditions in Eastern China. Our between-site comparison revealed slight differences in SOC storage and a similar vertical SOC distribution pattern across soil depths of 0–60 cm. Between the two study sites, we found substantially different effects of biotic and abiotic factors on SOC distribution. Complex interactions involving indirect effects between soil, plants and macrobenthos (crabs) may influence SOC distribution at a landscape scale. Marked differences in the SOC determinants between the study sites indicate that the underlying driving mechanisms of SOC distribution are strongly system-specific. Future work taking into account complex interactions and spatial heterogeneity is needed for better estimating of blue carbon stock and dynamics. It points to the necessity of incorporating these indirect effects for better understanding the mechanisms underlying carbon stock in coastal ecosystems. It also calls attention to spatial heterogeneity and system specificity for estimating blue carbon stock and dynamics.By comparing between two inter-tidal salt marsh sites with similar habitat conditions in Eastern China, we observed minor differences in SOC storage and a similar vertical SOC distribution pattern across the soil depths of 0–60 cm. Despite these similarities, we found strongly different effects of biotic and abiotic environmental factors on SOC density distribution between the two study sites. Complex interactions involving indirect effects between soil, plants and macro-benthos (crabs) can provide important additional explanatory power to the models explaining SOC distribution, suggesting that these interactions may underpin SOC distribution at a landscape scale. Marked differences in the SOC determinants between the study sites indicate that the underlying driving mechanisms of SOC distribution are strongly system-specific. Future work, taking into account spatial heterogeneity and system specificity, is needed for improving the accuracy of estimates of blue carbon stock and dynamics.


The current pandemic due to the coronavirus disease 2019 (COVID-19) outbreak has forced physicians to review their current clinical practice and guidelines. Although elective procedures using assisted reproductive technologies (ART) should be preferably canceled or postponed at this time, this does not always apply to urgent procedures such as those in patients with cancer. A complete oncofertility counseling balancing the benefits and risks of undergoing fertility preservation before commencing gonadotoxic therapies (chemotherapy and/or radiotherapy) should also be provided during the COVID-19 outbreak. This article briefly highlights what patients, oncologists and fertility specialists need to keep in mind during oncofertility counseling at the time of the COVID-19 outbreak. Some anticancer treatments can affect fertility , 2. OncoPatients face hurdles that can be as basic as getting to the tertiary hospital that offers both cancer care and fertility preservation treatments to more complex emotional thoughts dealing with the fear of both the known and unknown risks of complications from COVID-19 during cancer treatment and the additional fertility preservation treatments involving further hospital visits, potential surgery and in some units additional costs relating to COVID-19 testing and personal protective equipment (PPE) gear. Moreover, the anxieties from the fear of contracting the virus during hospital visits leading to isolation and quarantine are real enough for some to even consider opting out of fertility preserving treatments whilst fighting their most basic desire to procreate. For healthcare providers, the novel challenges of providing safe and optimal care while dealing with the undefined risks remain.Nonetheless, where resources allow, with extra caution and strict adherence to the COVID-19 safety protocols and local guidelines, oncofertility is a feasible option, giving hope for young patients with cancer.Newly diagnosed eligible cancer patients should discuss before commencing treatment with their oncologist and oncofertility specialists the wish to have children to see if it is possible to safely balance this option without compromising their cancer care and further increase the risk of infections by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Outline various fertility preservation procedures that can be undertaken safely with the precautions recommended by various national and international organizations including having protected pathways.For male patients, sperm banking before starting anticancer treatments is standard of care.For female patients, embryo/oocyte cryopreservation before starting anticancer treatments is the first option to be discussed .Ovarian tissue cryopreservation in patients that cannot wait 2-3 weeks before starting anticancer treatments can be discussed .Ovarian transposition can be considered before starting pelvic radiotherapy .Temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) during chemotherapy is an available option to protect ovarian function during treatment .Detailed oncofertility counseling should clearly discuss the additional concerns during the COVID-19 outbreak whist defining all the established safety protocols in place to minimize these risks.Triage patients for SARS-CoV-2 testing in accordance with local guidelines before starting any of the ART procedures.Train additional members of the team  on how to refill the liquid nitrogen tanks in case the lab staff is quarantined.If local resource allocation allows, consider having two teams  working by rota. An alternate team can take over in case one team comes in contact with an infected patient .The advances in oncofertility have given a lot of hope on preserving future fertility to cancer patients. Hence, we urge oncologists and fertility specialists to consider oncofertility counseling (which includes COVID-19-related safety concerns at this time) and work as a dedicated team to support young cancer patients optimizing their future fertility and reproductive health even during this pandemic. Let us not allow the COVID-19 outbreak to sidetrack us on this important issue.Tanya Buckshee Rohatgi has no conflicts of interest. Bhawna Sirohi has received honoraria from Bayer and Roche outside the submitted work . Matteo Lambertini acted as a consultant for Roche, and received honoraria from Theramex, Takeda, Roche, and Lilly outside the submitted work.No funding was received for this work.


Salmonella (NTS) enterica subspecies enterica is associated primarily with a self-limiting diarrhoeal illness, invasive bacterial infections  were also reported. Human outbreaks of NTS were reported in several countries all over the world including developing as well as high-income countries. Conventional laboratory methods such as pulsed field gel electrophoresis (PFGE) do not display adequate discrimination and have their limitations in epidemiological surveillance. It is therefore very crucial to use accurate, reliable and highly discriminative subtyping methods for epidemiological characterisation and outbreak investigation.Salmonellosis is one of the most common foodborne diseases worldwide. Although human infection by non-typhoidal Salmonella Typhimurium and Salmonella Dublin that occurred in 2013 in UK and Ireland respectively.Here, we used different whole genome sequence (WGS)-based subtyping methods for retrospective investigation of two different outbreaks of Salmonella Typhimurium genomes revealed well supported clades, that were concordant with epidemiologically defined outbreak and confirmed the source of outbreak is due to consumption of contaminated mayonnaise. SNP-analyses of Salmonella Dublin genomes confirmed the outbreak however the source of infection could not be determined. The core genome multilocus sequence typing (cgMLST) was discriminatory and separated the outbreak strains of Salmonella Dublin from the non-outbreak strains that were concordant with the epidemiological data however cgMLST could neither discriminate between the outbreak and non-outbreak strains of Salmonella Typhimurium nor confirm that contaminated mayonnaise is the source of infection, On the other hand, other WGS-based subtyping methods including multilocus sequence typing (MLST), ribosomal MLST (rMLST), whole genome MLST (wgMLST), clustered regularly interspaced short palindromic repeats (CRISPRs), prophage sequence profiling, antibiotic resistance profile and plasmid typing methods were less discriminatory and could not confirm the source of the outbreak.Single nucleotide polymorphism (SNP)-based cluster analysis of Foodborne salmonellosis is an important concern for public health therefore, it is crucial to use accurate, reliable and highly discriminative subtyping methods for epidemiological surveillance and outbreak investigation. In this study, we showed that SNP-based analyses do not only have the ability to confirm the occurrence of the outbreak but also to provide definitive evidence of the source of the outbreak in real-time. Salmonella enterica, which includes more than 2600 serovars [Salmonella infections are classically divided into diseases caused by typhoidal or non-typhoidal salmonella (NTS). Typhoid fever is caused by the human restricted Salmonella enterica serovars Typhi and Paratyphi [Salmonella (NTS) serovars, predominantly cause a self-limiting diarrhoeal illness they have adapted to cause invasive extra-intestinal disease known as invasive NTS (iNTS) which can result in bacteraemia and focal systemic infections [Salmonella serovars responsible for typhoid fever kill over 250,000 humans per year [Salmonella (NTS) serovars responsible for diarrhoeal illness cause over 155,000 deaths annually [Salmonella Typhimurium and Salmonella Dublin have been associated with systemic illness [Salmonella Typhimurium and Salmonella Dublin were reported in developed countries [Foodborne salmonellosis is an important concern for public health. It is caused by the enteric pathogen serovars . Human Sfections , 4 . Thefections  moreoverper year  while noannually . Interesannually . Salmoneountries –11.Salmonella enterica and have their limitations in epidemiological surveillance, it is therefore crucial to use accurate, reliable and highly discriminative subtyping methods for epidemiological characterisation and outbreak investigation.Conventional laboratory methods such as pulsed field gel electrophoresis (PFGE) do not usually provide adequate discrimination among outbreak and non-outbreak strains of Salmonella Typhimurium and Salmonella Dublin that occurred in 2013 in UK and Ireland respectively [Here, we evaluate different whole genome sequence (WGS)-based subtyping methods (including single nucleotide polymorphism (SNP)-based cluster analysis, multilocus sequence typing (MLST), ribosomal MLST (rMLST), whole genome MLST (wgMLST), core genome MLST (cgMLST) as well as clustered regularly interspaced short palindromic repeats (CRISPRs), prophage sequence profiling, antibiotic resistance profile and plasmid typing) for retrospective investigation of two outbreaks of ectively , 12.Salmonella Dublin that occurred in 2013 in Ireland [Salmonella Typhimurium occurred in 2013 in UK [Salmonella Typhimurium and Salmonella Dublin respectively. Non-outbreak strains were also included for comparison. Details of all Salmonella Dublin and Salmonella Typhimurium isolates analysed in this study are provided in supplementary Tables We carried out retrospective investigation of a human outbreak of  Ireland  and anot13 in UK . We inclSalmonella Dublin [Salmonella Dublin were indistinguishable by PFGE. Although multiple loci VNTR analysis (MLVA) was of value in discriminating the outbreak strains from an epidemiologically unrelated isolate in 2013 it was not able to provide a conclusive link between the outbreak strain and a historical isolate from 2011 (11F310) since all outbreak strains had the same MLVA pattern (3-6-1-10-2-3-12) and the historical isolate had similar MLVA pattern (3–6–1-10-2-3-11/12).PFGE was of a limited value for the investigation of the outbreak of a Dublin  since alSalmonella Typhimurium [Despite the technical limitation of phage typing, it was of value for investigating the outbreak of himurium  and confdenovo assembly for the raw Fastq paired end (PE) reads for all Salmonella Dublin and Salmonella Typhimurium strains using two different assemblers including Velvet available at Centre for genomic epidemiology (CGE) (http://www.genomicepidemiology.org/) and SPAdes available at Enterobase (http://enterobase.warwick.ac.uk/). We then assessed the quality of the assembly for each strain was assessed using Quast assessment tool (http://quast.bioinf.spbau.ru/).We carried out https://cge.cbs.dtu.dk/services/CSIPhylogeny/) where raw reads were mapped to reference sequences  using BWA software (http://bio-bwa.sourceforge.net). The depth at each mapped position was calculated using genomeCoverageBed, which is part of BEDTools (https://bedtools.readthedocs.io/en/latest/). High quality SNPs were called using mpileup which is part of SAMTools (http://samtools.sourceforge.net). Genome mappings were then compared and an alignment of the SNPs are then created by concatenating the SNPs. A maximum likelihood (ML) phylogenetic tree was then created based on the concatenated alignment of the high quality SNPs.SNP analysis was carried out using CSIPhylogeny (http://enterobase.warwick.ac.uk/) and CGE (http://www.genomicepidemiology.org/).The assembled sequences of each strain were analyzed to detect the MLST, rMLST, cgMLST and wgMLST available at Enetrobase .Prophages were determined with the draft genomes generated by Velevt and SPAdes for all http://www.genomicepidemiology.org/) to construct a phylogenetic tree based on the SNPs of detected prophages. Phylogenetic trees were constructed using assembled genomes generated by Velvet and SPAdes assemblers to check if the assembly could affect the tree.We then used CSI phylogeny available at CGE .Spacers sequence within the draft genomes of all Salmonella Dublin and Salmonella Typhimurium strains using the plasmid database; PLSDB (https://ccb-microbe.cs.uni-saarland.de/plsdb/).We determined the plasmids within the draft genomes of all Salmonella Dublin and Salmonella Typhimurium strains using ResFinder (https://cge.cbs.dtu.dk/services/ResFinder/).We determined acquired antibiotic resistance genes and mutations within the draft genomes of all Salmonella Typhimurium were grouped together in two clades and they are very closely related to strains isolated from mayonnaise . Interestingly, outbreak isolates of Salmonella Dublin displayed identical rMLST (type 1429) however, some of the non-outbreak strains showed the same rMLST. Moreover, the wgMLST was different among the outbreak strains however, the cgMLST was unique among outbreak strains and can easily separate the outbreak strain from the non-outbreak strains including the 2011 historical isolate (11F310).As illustrated in Table Salmonella Typhimurium as illustrated in Table On the other hand, MLST, rMLST, cgMLST and wgMLST could not discriminate between the outbreak and non-outbreak strains of Salmonella Dublin isolates including outbreak and non-outbreak strains harbour one CRISPR locus and we observed 3 to 5 unique spacers for CRISPR1 locus. Identical spacers were detected among the outbreak and non-outbreak strains as shown in Table All Interestingly, the number of spacers in three isolates  changed from (4 spacers) based on Velvet to (5 spacers) based on SPAdes.Salmonella Typhimurium isolates harbour 3 CRISPR loci. Identical spacers were detected among the outbreak and non-outbreak strains as shown in Table All Salmonella Dublin strains including the outbreak strains are lysogenic for three prophages . However, phylogenetic analyses of Salmonella Dublin strains based on the SNPs of prophages showed that outbreak strains are intermixed with the non-outbreak strains based on velvet assembler  and the Edwardsiella specific phage (GF-2).All Salmonella Typhimurium genomes assembled by Velvet were lysogenic for two Salmonella specific prophages (Gifsy 2 and RE-2010). All strains except one outbreak isolate (H132940750) harbour Salmonella 118970_sal3 phage.On the other hand, Interestingly, all strains harbour Edwardsiella GF-2 prophage except three outbreak isolates .Salmonella Typhimurium strains based on the SNPs of prophages showed that outbreak strains are intermixed with the non-outbreak strains using velvet assembler  as shown in Table All outbreak and non-outbreak strains of Same plasmids were determined using Velvet and SPAdes assemblers.Salmonella Typhimurium harbour 3 plasmids  except the outbreak strain H133300609 which did not carry plasmid pATCC14028 but it harbours a different plasmid (pSLT_VNP20009) instead -Iaa gene. No mutations were detected against gyrA and parC genes in all isolates except one isolate (MF038630) that carried a non-synonyms mutation within the gyrase protein and it is associated with bacterial resistance to nalidixic acid -Iaa gene”. No known mutations were detected against gyrA and parC -based cluster analysis of Salmonella Typhimurium strains. However, cgMLST defined the genetic relatedness among Salmonella Dublin isolates more precisely and confirmed there is no relation among the 2013 outbreak isolates and the 2011 historical isolate (11F310) of Salmonella Dublin.On the other the WGS-subtyping methods including MLST, rMLST, wgMLST, cgMLST showed limited discrimination for the outbreak and non-outbreak isolates of It was reported that MLST might not be the most suitable epidemiological tool  but it iThe cgMLST bridges the classic MLST with the novel WGS-based approach since it combines the discriminatory power of MLST with large-scale data obtained from WGS enabling to exploit a considerable number of gene targets throughout the bacterial genome which would maximize the quality and resolution for surveillance and research works.Salmonella Enteritidis in Europe [A recent study showed that cgMLST has shown the robustness of cgMLST as a tool to investigate multi-country outbreak of n Europe .Escherichia coli (VTEC) O157:H7 in Canada showed that wgMLST provided higher discrimination than PFGE and MLVA [The difference between the cgMLST and wgMLST is that unlike cgMLST, wgMLST indexes the variation of pre-defined set of genes from both core and accessory genes . Anotherand MLVA .Salmonella Dublin isolates of outbreak group from the non-outbreak group. However, both cgMLST and wgMLST were unsuccessful in differentiating outbreak-related Salmonella Typhimurium isolates from outbreak-unrelated isolates.Research studies have shown that cgMLST and wgMLST are viable typing methods for outbreak surveillance. In our study, cgMLST proved to provide higher discriminatory resolution for differentiating Salmonella serovars [Salmonella subtyping is the sensitivity and accuracy of the assembly as some prophage regions might be lost during assembly. We used two different denovo assemblers (SPAdes and Velvet) and found that prophage sequence profiling could not differentiate between the outbreak and non-outbreak isolates.Bacterial genome comprises a considerable amount (10 to 20%) of prophages integrated in their core genome . Prophagserovars . HoweverSalmonella outbreaks [Salmonella enetrica outbreaks as we showed in our previous studies [Salmonella serovars.Recent studies have suggested that high throughput CRISPR typing has the potential to be used for epidemiological surveillance and investigation of utbreaks , 27. How studies , 29 howePlasmid profiles and antimicrobial- susceptibility profiling have been used as an epidemiological tool since many decades. However, it was reported that analysis of plasmid profiles provided higher discrimination in the outbreak investigations than analysis of antimicrobial-susceptibility pattern , 31. In In this study, we compared several retrospective WGS-based subtyping methods and we showed that SNP-based cluster analysis is superior to other subtying methods to define the source of outbreak in real-time.In conclusion, foodborne salmonellosis is an important concern for public health therefore, it is crucial to use accurate, reliable and highly discriminative subtyping methods for epidemiological surveillance and outbreak investigation. The rapid development of next-generation sequencing (NGS) technology and bioinformatics tools have enabled WGS of any bacterial strain feasible. Various typing tools have been proposed by using WGS data but currently, the adoption of WGS-based methods have proved to be difficult due to lack of standardization. There are many layers on obtaining WGS data and there is need of standardization from the type of sequencers used to the bioinformatics analysis. Therefore, the emerging genetic analysis techniques should be combined with conventional phenotypic and molecular methods for routine surveillance and outbreak investigation until the WGS-based methods can be fully exploited, improved and standardized.Additional file 1: Supplementary Table 1. Details of Salmonella Dublin strains analysed in this study. Supplementary Table 2. Details of Salmonella Typhimurium strains analysed in this study


Dual-task gait performance is a marker of motor-cognitive interactions modulated by the frontal lobes. After a stroke, gait disturbances are more evident, particularly when concurrently completing a mental task and walking, an effect called high dual-task cost (DTC). Following a stroke, the potential association of high-DTC, integrity of the frontal lobes and cognitive functioning is unclear. This study screened 161 participants with stroke history from the Ontario Neurodegenerative Disease Research Initiative (ONDRI)-cerebrovascular disease cohort . Individuals scoring zero in the National Institute of Health Stroke Scale were analyzed (n=102). DTC was the percentage change in gait speed from the single to dual-task condition. Standardized normal-appearing white matter (NAWM) and grey matter (NAGM) volumes from superior, middle and inferior frontal lobe were compared between DTC quartiles  using a multivariate model (MANOVA), with total frontal lobe volume as a covariate. Another model compared group performance across 5 adjusted cognitive domains . Univariate tests revealed that NAWM volume in the superior frontal lobe  was significantly different across DTC quartiles. Contrast tests suggested that the first quartile had larger NAWM than the second and fourth. DTC quartiles also showed differences in attention  and contrast tests indicated that the first quartile performed significantly better than second and fourth. DTC poststroke may be a proxy for structural integrity of superior frontal lobe regions and attention.


Microbacteriaceae from plants infested by plant-parasitic nematodes were obtained using Illumina technology. The sequence data will provide useful baseline information for the development of comparative genomics and systematics of Microbacteriaceae and facilitate understanding of molecular mechanisms involved in interactions between plants and nematode-associated bacterial complexes.Draft genome sequences of 28 strains of  Microbacteriaceae from plants infested by plant-parasitic nematodes were obtained using Illumina technology. The sequence data will provide useful baseline information for the development of comparative genomics and systematics of Microbacteriaceae and facilitate understanding of molecular mechanisms involved in interactions between plants and nematode-associated bacterial complexes.Draft genome sequences of 28 strains of  Microbacteriaceae (class Actinobacteria) inhabit various terrestrial and aquatic ecosystems and often occur in plants as endophytes and pathogens   , 4. Alonragariae , 5–8.Microbacteriaceae were isolated from plant galls induced by different anguinids and from plant tissues affected by Aphelenchoides species (Corynebacterium agar (http://www.vkm.ru).Novel nematode-associated strains of  species . The airium agar  or Reasoium agar , 11 and For genome sequencing, DNA was extracted with a QIAamp DNA minikit  from biomass grown in liquid peptone-yeast medium as described previously  or usingDefault parameters were used for all software unless otherwise specified. The quality of the reads was checked with FastQC 0.11.8 . AdapterAdditional comparative phenotypic study of the sequenced strains, along with genome-wide analyses of phylogenetically closely related plant endophytes and pathogens, will facilitate understanding of their role in bacterial-nematode complexes, including mechanisms of molecular interactions between members of these complexes and plants.These whole-genome shotgun projects have been deposited in DDBJ/ENA/GenBank under the accession numbers listed in


Despite some insurance plans now paying for home-based palliative care, recent reports have suggested that coverage for palliative care may be insufficient to expanding patient access to home-based palliative care. Research has yet to explore palliative care barriers from the perspective of palliative care-eligible patients and their caregivers. To identify patients and caregivers’ perceived barriers to home-based palliative care and their recommendations for overcoming these barriers, we conducted a qualitative study using semi-structured individual interviews. Participants  who were eligible for a randomized controlled trial of home-based palliative care were interviewed via telephone. Our interview protocol elicited participants’ perspectives on home-based palliative care services; positive and negative aspects of the program explanation; and suggestions for improving messaging around home-based palliative care. Researchers used grounded theory to identify the themes within the transcripts. Two researchers independently coded the transcripts and then met to compare coding and reconciled discrepancies until 100% consensus was reached. Identified themes related to home-based palliative care referral barriers included reluctance to have home visits, timing, lack of palliative care knowledge, misconceptions of palliative care, and patients’ self-perceived health condition . Themes related to recommendations for overcoming these barriers included preferring a palliative care referral from healthcare providers or from insurance company and clearer presentation of palliative care service. Findings reinforce the need for additional palliative care education among patients with serious illness and the importance of delivering the information from a trusted source.


Physical frailty is an age-related clinical syndrome that is related to adverse health outcomes, including cognitive impairment and dementia. Recent studies have shown structural neuroimaging correlates with frailty. However, most existing evidence relies on brain volumetric measures. Whether brain microstructure is associated with frailty and its spatial distribution have not been explored. In the Baltimore Longitudinal Study of Aging, we identified 776 cognitively normal participants aged 50 and older who had concurrent data on frailty and brain microstructure by diffusion tensor imaging (DTI), including mean diffusivity (MD) of gray matter and fractional anisotropy (FA) of white matter. We first identified neuroimaging markers that were associated with frailty score (0-5) and further examined their relationships with frailty status  using multivariate linear regression. Models were adjusted for age, sex, race, years of education, and Apolipoprotein E e4 carrier status. DTI-based neuroimaging markers that were associated with frailty status were localized in the supplementary motor area of the frontal lobe, several subcortical regions , and body and splenium of corpus callosum. This study demonstrates for the first time that microstructure of both gray and white matter differs by frailty levels in cognitively normal older adults. Brain areas were not widespread, but mostly localized in gray matter subcortical motor areas and white matter corpus callosum. Whether changes in brain microstructure precede future frailty development warrants further investigation.


Sambucus nigra lectin-reactive) fibronectin in prediction of gestational diabetes mellitus (GDM).To evaluate the performance of first trimester maternal serum glycosylated . There was no difference in assay formats for adiponectin.There was no difference in maternal serum glycosylated fibronectin concentrations between women with consequent GDM  and control women . Maternal serum fibronectin levels were significantly lower in GDM group , compared to the control group  fibronectin and GDM. Meanwhile, this study provides information on the screening performance of glycosylated fibronectin in women with GDM. This study also evaluated glycosylated fibronectin levels in different BMI subgroups.According to our results, neither first trimester maternal serum glycosylated fibronectin nor serum fibronectin are effective in screening for GDM. Further larger studies in prospective settings are needed to evaluate first trimester glycosylated fibronectin as a screening method for GDM alone and in combination with other markers.


Central retinal artery occlusion (CRAO) represents one of the most devastating ophthalmic emergencies, since the inner two-thirds of the retina lose their blood supply. The acute obstruction of the central retinal artery is characterized by severe, sudden and unilateral painless visual loss and usually occurs secondary to an embolus of cardiovascular origin. A paradoxical thromboembolic event of the central retinal artery through patent foramen ovale is an exceptionally unusual clinical entity as well as a great diagnostic challenge since the source of initial thrombus formation requires extensive investigation. Herein, we aim to describe a patient with no significant comorbidities who experienced a paradoxical thromboembolic episode of central retinal artery associated with patent foramen ovale. Central retinal artery occlusion represents the ophthalmic analogue of ischemic stroke and is typically manifested with sudden, severe and painless loss of vision . HoweverCRAO is usually the result of an embolus, either of cardiac origin or dislodged from an unstable atherosclerotic plaque of carotid bifurcation. Subsequently, the most common risk factors for CRAO include carotid atherosclerosis, cardiac valvular disease and cardiac arrhythmias, mainly atrial fibrillation . CongeniThe most important and well-documented clinical manifestation of PFO is the cryptogenic ischemic stroke due to a paradoxical embolus. CRAO or branch retinal artery occlusion (BRAO) associated with PFO represents an unexpected site of systemic paradoxical embolism that requires high index of clinical suspicion and meticulous laboratory investigation in order to unravel the concealed initial source of thrombus generation .Herein, we aim to present a middle-aged male patient who experienced an episode of severe, painless and unilateral visual loss due to CRAO associated with PFO. We also discuss the clinical complexity of such a diagnosis as well as we briefly review the current literature regarding similar published case reports.A 62-year-old Caucasian male, with no previous ocular or neurological symptoms, experienced a sudden and painless loss of vision in the left eye while swimming. He had no significant past medical history apart from an episode of deep vein thrombosis of the left lower extremity four years ago, provoked by a non-displaced fracture of the tibia after a motor vehicle accident. He also reported a previous history of hospitalization due to an episode of acute left-sided loin pain associated with macroscopic haematuria at the age of 60 years. Then the patient had been thoroughly investigated and no specific diagnosis of renal infarct of unknown origin had been made. Otherwise, he did not take any regular medication and he neither smoked tobacco nor drank alcohol.On initial examination, he was afebrile and his pulse rate was 82/min and regular. His blood pressure was 130/85 mmHg and there were no abnormalities to find in the cardiovascular or respiratory systems. No carotid or over the umbilicus bruits were audible and pedal pulses were palpable. Physical examination was otherwise normal apart from a clearly swollen left lower extremity accompanied with engorged superficial veins, hyperpigmentation and trophic skin changes. On palpation, there was no tenderness of his left calf muscles and no venous ulcerations were observed. As regards neurological examination it was also unremarkable including the muscle tone, reflexes, coordination and sensation as well as power, in all muscle groups. Afterwards, the patient was immediately evaluated on the basis of fundoscopic examination that revealed left retinal whitening, macular edema and cotton-wool spots compatible with CRAO Figure . The aboOnce CRAO with sparing of cilioretinal artery diagnosis had been made, a meticulous investigation was performed in order to unwind the thread of this unanticipated thromboembolic event.Routine hematological and biochemical investigations were unremarkable barring the slightly elevated creatinine and urea levels, up to 1.6 mg/dL and 60 mg/dL respectively, but accordant with a prolonged history of chronic kidney disease stage III with GFR estimated at 46ml/min/1.73m2. Inflammatory markers (C- Reactive Protein and Erythrocyte Sedimentation Rate) and clotting parameters including d-dimers and fibrinogen levels were within normal values. Further investigation for autoimmune diseases, occult infectious conditions and thrombophilic disorders were also negative. More specifically, thrombophilia testing was performed including factor V Leiden, prothrombin gene mutation, antithrombin III, protein C and protein S, lupus anticoagulant screen as well as antinuclear antibodies, anti-dsDNA antibodies, anti-cardiolipin antibodies (ACA) and anti-beta 2 glycoprotein antibodies (anti-β2GPI).Regarding radiological examination, a renal ultrasound confirmed the previously mentioned asymmetrical kidney size and showed a small as well as echogenic left kidney, consistent with the past history of renal infarction without apparent cause. Carotid Doppler ultrasound did not identify any extracranial vulnerable atherosclerotic plaque potentially at risk for disruption and thromboembolic ischemic retinal event. Similarly, abdominal aorta ultrasound imaging and ultrasonographic assessment of renal arteries did not depict any atherosclerotic lesions that could be possibly the source of the reported renal vaso-occlusive event.Venous ultrasound imaging unveiled no relapse of the previously recorded deep vein thrombosis although the diagnosis of post-thrombotic syndrome was made on the basis of post-thrombotic popliteal valve incompetence accompanied with significant reflex at the same level. Residual thrombi were also recognized mainly in the left popliteal vein and partially recanalization of both popliteal and gastrocnemius veins was described. Residual thrombi in left popliteal vein raised the question of whether a paradoxical embolus could explain not only the CRAO event but also the past embolic event in renal artery circulatory system.With the completion of these steps, a meticulous cardiologic examination was undertaken and included 48-hour Holter monitoring and transthoracic echocardiography followed by bubble contrast echocardiography testing. Holter monitoring results excluded the possibility that CRAO event could be correlated with an obscured supraventricular arrhythmia, predominantly an episode of paroxysmal and symptomless atrial fibrillation. Transthoracic echocardiography examination also eliminated the option that the embolic event originated from a cardiac valvular defect. Surprisingly, bubble contrast echocardiography testing revealed more than 25 saline microbubbles in the left atrium of the heart at the first three cardiac cycles while the patient was asked to perform a Valsava maneuver  in a quarter of the population .The frequency and significance of PFO in association with ocular circulatory disturbances were evaluated in forty patients with acute arterial occlusions of the posterior bulb segment through transthoracic and transesophageal echocardiography by Steuber and colleagues . PFO wasCertainly, the emerging association between undiagnosed PFO and retinal artery occlusion has been predominantly reported in young patients. An example of this is the report of a 35-year-old man with branch retinal artery occlusion (BRAO) and concomitant PFO, which was firstly diagnosed during the evaluation of BRAO, by Chatziralli and colleagues . In a siHence, it could be conceivably argued that retinal artery occlusion in an otherwise healthy adult patient, should always consider the PFO as a differential that requires meticulous cardiologic examination. Despite the fact that transesophageal echocardiography (TEE) is a potentially useful and effective tool for detecting possible sources of retinal artery emboli , in our Patent foramen ovale (PFO) is a common congenital intracardiac defect that can cause right-to-left shunting under certain conditions and may predispose individuals to paradoxical embolic events from the venous to arterial district. Rarely, PFO has been correlated to central retinal artery occlusion and branch retinal artery occlusion with visual sequelae not only in young but also in advanced-aged patients at low atherosclerosis or cardioembolic risk, concomitant with a propensity for deep vein thrombosis.


Pharmacoresistance and adverse drug events designate a considerable group of patients with focal epilepsies that require alternative treatments such as neurosurgical intervention and neurostimulation. Electrical or magnetic stimulations of cortical brain areas for the treatment of pharmacoresistant focal epilepsies emerged from preclinical studies and experience through intraoperative neurophysiological monitoring in patients. Direct neurostimulation of seizure onset zones in neocortical brain areas may specifically affect neuronal networks involved in epileptiform activity without remarkable adverse influence on physiological cortical processing in immediate vicinity. Noninvasive low-frequency transcranial magnetic stimulation and cathodal transcranial direct current stimulation are suggested to be anticonvulsant; however, potential effects are ephemeral and require effect maintenance by ongoing stimulation. Invasive responsive neurostimulation, chronic subthreshold cortical stimulation, and epicranial cortical stimulation cover a broad range of different emerging technologies with intracranial and epicranial approaches that still have limited market access partly due to ongoing clinical development. Despite significant differences, the present bioelectronic technologies share common mode of actions with acute seizure termination by high-frequency stimulation and long-term depression induced by low-frequency magnetic or electrical stimulation or transcranial direct current stimulation. Epilepsies are characterized by unpredictable seizures and affect more than 70 million people worldwide Beghi . Focal sPharmacoresistance and TEAEs designate a considerable group of patients with focal epilepsies that requires alternative treatments such as neurosurgical intervention and neurostimulation. Whereas neurosurgical resection can only be applied to non-eloquent brain areas in a minority of patients  that compared repetitive TMS with sham or placebo controls  in the period from 2014 to 2018 as compared to the meta-analysis done in 2014 by the same group  on a localized epileptic focus  was significantly larger than in the sham patients (17%)  (Xia and Storm LFS induces LTD by N-Methyl-D-aspartate (NMDA) receptor activation and the subsequent slight increase in CaNoninvasive cathodal tDCS is suggested to provoke transient and long-term effects on cortical excitability (Antal et al. Electrical or magnetic stimulations of cortical brain areas for the treatment of pharmacoresistant focal epilepsies emerged from preclinical studies and experience from intraoperative neurophysiological monitoring in patients Table . Noninva


Oregon’s Behavioral Health Initiative for Older Adults and People with Disabilities is entering its fifth year. This novel state-level Initiative seeks to better coordinate services and resources for older adults and people with disabilities who have behavioral health needs by assigning a Behavioral Health Specialist (BHS) for every 60,000 adults 65 + and embedding them within local service agencies around Oregon. BHS primary job functions include improving coordination and collaboration between local service agencies, providing complex case consultations (CCC), and delivering workforce development training and community education. Five years of data from Portland State University’s Institute on Aging’s ongoing evaluation of the Initiative suggests significant impact in terms of workforce development trainings, community education, and new community partnerships. Data are collected from BHS and Initiative stakeholders . Data collection tools include quarterly reports from the BHS, including a CCC reporting instrument; semi-structured interviews with stakeholders assessing Initiative involvement; and an electronic post-training survey (and two-month follow-up survey) for stakeholders attending BHS trainings. After five years, the evaluation appears to show the Initiative has delivered an abundance of innovative collaborations, workforce trainings, and educational opportunities aimed at better supporting the behavioral health of older Oregonians. It also highlights several persistent systemic barriers including a need for additional public funding of behavioral health, the challenges of accessing Medicare for behavioral health, and siloed agencies and organizations. Future evaluative efforts could explore adding outcomes-based assessments of the Initiative, including local-level quality improvement projects initiated by BHS within their communities.