The management of unruptured cerebral aneurysms in elderly patients remains controversial.Key challenges including frailty, cognitive dysfunction, reduced life expectancy, vasculopathy and poor prognosis with aneurysm rupture add complexity to endovascular and surgical decision making not encountered with younger demographics.A thorough understanding of available treatment options, likelihood of treatment success and associated risks weighed against the risk of aneurysm rupture informs patient discussion and management.Unruptured cerebral aneurysms are increasingly identified in elderly patients as the global life expectancy continues to rise and non-invasive vascular imaging becomes more prevalent. The optimal management of unruptured aneurysms in elderly patients remains controversial. Variability in life expectancy, comorbidities and rupture risk coupled with heterogenous endovascular and surgical treatments contribute to a paucity of clear guidelines, and current management is highly individualized. Elderly patients present unique considerations including frailty, cognitive dysfunction, vasculopathy, reduced life expectancy and overall worse prognosis in case of rupture which shape the risks and likelihood of success of endovascular and microsurgical treatment. In this review, we provide a comprehensive overview of unruptured cerebral aneurysms in the elderly, with a particular focus on the natural history, key challenges associated with advanced age, management and future innovations to further refine treatment. Life expectancy is increasing at unprecedented rates. By 2050, the proportion of individuals 65 years or older will more than double from 8.1% to 21% [Multiple guidelines regarding the management of unruptured cerebral aneurysms in the general population have been established by cornerstone neurosurgical trials . OptimalThe prevalence of unruptured cerebral aneurysms in the elderly and the association between age and aneurysm development remain controversial. Several autopsy reports describe an increased prevalence of unruptured cerebral aneurysms with advancing age. Inagawa et al. reviewed 10,259 autopsies performed in New York, NY and found the incidence of unruptured cerebral aneurysms highest in patients over 60 years, with a peak prevalence of 1.2% in the seventh decade of life . In the The incidence of aneurysm rupture and association with advanced age has been evaluated in multiple prospective studies. In the general population, the overall risk of rupture per patient-year at risk is 0.6–1.3% . The IntThe overall rupture rate in elderly patients appears similar to the general population. A pooled analysis evaluating 1896 patients 70 years and older with 2227 unruptured aneurysms reported an annual rupture rate of 1.6% . AdditioFrailty is defined as a decrease in homeostatic reserve and is closely associated with increasing age . FrailtyNumerous attempts have been made to quantify frailty based on phenotypic characteristics, functional deficits, social situations and medical comorbidities, with the modified frailty index (mFI) representing a well establish metric of physiologic reserve. Including five (mFI-5) or eleven (mFI-11) factors, based on the original 70-item Canada Study of Health and Ageing Frailty Index, the mFI predicts morbidity and mortality across all subspecialties . In neurBrain frailty resulting from intrinsic damage to small perforating arterioles, endothelial dysfunction, blood–brain barrier breakdown and inflammation is an additional marker of poor cerebral reserve in elderly patients, and is readily evident on advanced imaging as white matter hyperintensities, microbleeds, prominent perivascular spaces, lacunar infarcts and cerebral atrophy. Baseline brain frailty scores on magnetic resonance imaging and computed tomography are associated with poor functional outcomes following lacunar and non-lacunar stroke . Brain fPreserved cognitive function is particularly relevant in elderly patients, as any neuropsychological decline either from the anxiety of harbouring an unruptured aneurysm or as a direct consequence of treatment may have dramatic consequences on quality of life, independence and overall life expectancy. Patients with unruptured cerebral aneurysms may harbour cognitive impairments at baseline, which can influence long-term outcomes. Fukunaga et al. evaluated 30 patients with unruptured cerebral aneurysms and described neuropsychological impairment in three . Haug etCurrent literature is inconclusive regarding cognitive outcomes following elective aneurysm treatment. ISUIA reported impaired cognitive function in 3.2–7.1% of patients who underwent either clipping or coiling at 1 year after treatment . Particuvs. after treatment of an unruptured aneurysm. Srivatsan et al. evaluated Montreal Cognitive Assessment scores following elective coiling of unruptured aneurysms in 33 patients and found no difference compared to baseline scores [Additional studies, however, report no difference in cognitive function before e scores . Similare scores . Few stue scores .Given the lack of definitive guidelines, conflicting outcomes regarding cognitive function following treatment, and few studies in the elderly, neurocognitive prognosis must be highly individualized. New evaluations in elderly patients should emphasize the anxiety of harbouring an unruptured aneurysm, which may improve with definitive aneurysm repair. Cerebrovascular cognitive reserve, baseline ischaemic white matter disease and evidence of vascular cognitive impairment are particularly important. Meticulous surgical dissection and endovascular technique may minimize parenchymal injury and preserve cognitive function post-operatively. Nevertheless, patients with extensive chronic ischaemic changes may be unfavourable candidates for treatment due to increased susceptibility to long-term neurocognitive changes, as seen in the landmark studies such as ISUIA .et al. performed a life expectancy analysis of patients with unruptured aneurysms with and without repair based on prospective data from ISUIA to identify circumstances under which aneurysm repair would be beneficial [The long-term risks of unruptured cerebral aneurysms in the elderly are challenging to determine based on the existing literature. As life expectancy declines, the likelihood of rupture combined with comorbidities that are more likely to cause death may call into question the benefit of aneurysm treatment. Vindlacheruvu neficial . They foPre-existing medical conditions and comorbidities, along with age, predict remaining life years following hospitalization. One year survival after first admission for heart failure or initiation of dialysis is 67% and 45.5%, respectively ,33. EldeChronic hypertension and atherosclerotic disease, common comorbidities that increase with advancing age, may accelerate vessel or aneurysm calcification, reduce arterial compliance, increase vessel tortuosity and narrow parent vessels, thereby complicating treatment. Atherosclerotic aneurysm calcification is more common in larger aneurysms and in older patients, and is associated with increased morbidity following clipping. In a study of 208 patients treated with clipping or coiling of unruptured aneurysms, the presence of calcification in an aneurysm was the sole marker of adverse outcome . In addiet al. found that arterial stenosis and tortuous anatomy limits the spread of microcatheter tension, may increase the risk of intra-procedural aneurysm rupture and plaque mobilization, decreases the rate of complete occlusion, and may necessitate the use of adjuvant stent or balloon assistance, which increases the risk of in-stent thrombosis and arterial dissection [Intracranial atherosclerotic disease adjacent to cerebral aneurysms also influences the efficacy and complication profile of endovascular treatment. Gao ssection . While essection .et al. analysed outcomes of elderly patients with aneurysmal subarachnoid haemorrhage stratified by age and clinical presentation [Advanced age is recognized as a poor prognostic indicator after subarachnoid haemorrhage, and the overall worse outcome in elderly patients following aneurysm rupture has important implications regarding patient counselling and management. Lanzino et al. evaluated the relationship between age and outcome in aneurysmal subarachnoid haemorrhage using data from the multicentre randomized trial of nicardipine in subarachnoid haemorrhage . They reentation . They reCoiling provides a minimally invasive alternative to open surgery for treatment of intracranial aneurysms. Coiling is generally the favoured treatment in elderly patients despite a lack of supportive randomized controlled trials. For ruptured aneurysms, the landmark International Subarachnoid Aneurysm Trial (ISAT) in 2002  and 2015Coiling of unruptured aneurysms in the elderly appears overall to be safe and effective. Hwang et al. coiled 122 saccular unruptured aneurysms in 96 consecutive patients 70 years or older; they successfully occluded the aneurysm with no adverse clinical events in 95.9% of cases . A meta-Elderly patients may be particularly prone to complications following coiling of unruptured aneurysms. Khosla et al. compared the complication profile associated with elective coiling of intracranial aneurysms between elderly and non-elderly patients, reporting major complications with and without neurologic disability more prevalent in patients 65 years and older . IschaemAdjuvant techniques for coil embolization, including balloon assistance and stent assistance, have been studied only modestly in the elderly, potentially due to their relatively infrequent usage. In a meta-analysis by Sturiale et al. evaluating 21 studies with 1511 elderly patients undergoing endovascular treatment of both ruptured and unruptured aneurysms, only 5% utilized balloon assistance and 3% utilized stent assistance . BalloonMicrosurgical clipping of unruptured aneurysms is a more invasive alternative to endovascular treatment, and elderly patients are less likely to tolerate clipping as compared to younger patients. Barker et al. compared age-dependent outcomes in 3498 patients who underwent clipping or coiling for unruptured aneurysms . When divia a supraorbital or pterional approach in 62 non-frail elderly and 198 non-elderly patients reported no increase in complication rates, hospital duration, aneurysm recurrence, morbidity or mortality with advanced age [via a supraorbital or pterional approach, sufficient drilling of the frontal skull base or sphenoid ridge, and wider subdural spaces in elderly patients improved aneurysm access and minimized excessive brain retraction, contributing to lower rates of neurological morbidity, mortality and cognitive dysfunction compared to standard clipping.Increased morbidity, mortality and institutionalization following discharge for microsurgical clipping of unruptured aneurysms in elderly patients suggests the need for less invasive surgical techniques focussed on minimal tissue disruption. The superciliary keyhole approach has been advocated as an alternative to pterional craniotomy for anterior circulation aneurysms, but validation in elderly patients has not been described . A retronced age . A minimFlow diverting stents are approved for the treatment of cerebral aneurysms of the internal carotid artery. Their reduced porosity creates a scaffolding for endothelialization across the cerebral aneurysm neck, reducing intra-luminal flow and allowing for slow obliteration. No recurrences have been reported once occlusion is achieved, and flow diversion has become a standard treatment for wide-necked saccular or fusiform internal carotid artery aneurysms for which traditional endovascular and surgical treatments are limited.Elderly patients have reduced but acceptable rates of aneurysm occlusion following flow diversion. Kuhn et al. evaluated the effects of age on aneurysm occlusion following flow diversion for treatment of unruptured cerebral aneurysms . At 12–1Older patients treated with flow diversion are more likely to harbour aneurysms of larger size, complex morphology and within the posterior circulation compared to younger counterparts which, along with increased frequency of comorbidities, atherosclerosis and arterial tortuosity, raises concern for increased morbidity and mortality. Brinjikji et al. reviewed age-related outcomes following pipeline reconstruction of unruptured aneurysms in 711 patients and found increasing age associated with higher neurological mortality . Patientvia inhibition of cyclooxygenase-2 (COX-2), supporting the inflammatory hypothesis of aneurysm formation and rupture [Aspirin lowers rates of aneurysm rupture in animal models  rupture . In a sm rupture .Preliminary prospective and retrospective studies suggest that aspirin is safe in patients with unruptured aneurysms and may lower the risk of aneurysmal subarachnoid haemorrhage. A prospective, multicentre observational study that followed patients with unruptured cerebral aneurysms and ischaemic cerebrovascular disease found that aspirin was safe in patients with concurrent small unruptured cerebral aneurysms and was associated with low rate of aneurysm rupture . Hasan eAspirin may also limit aneurysm growth. A prospective cohort study following 272 patients with unruptured aneurysms 7 mm or smaller, 113 of which were on aspirin continuously, found that aspirin was associated with a low risk of aneurysm growth . An addiStatins have anti-inflammatory effects in various vascular diseases, but their protective effects on the formation and progression of cerebral aneurysms remain unclear. A multicentre case–control study compared 117 patients with aneurysmal subarachnoid haemorrhage to 304 patients with incidental, unruptured cerebral aneurysms and found a lower rate of statin use in rupture cases, suggesting an inverse relationship between statin use and aneurysm rupture . AlternaFuture alternatives to stratify treatment decisions in high-risk elderly patients, evaluation of new endovascular devices and microsurgical innovation will continue to improve elderly patient outcomes. Wall enhancement on black-blood MRA, observed more frequently in unstable, growing and ruptured aneurysms ,73, may The optimum management of unruptured cerebral aneurysms in elderly patients remains undefined. The process of ageing presents unique considerations and challenges, and management is currently individualized, requiring precise knowledge of natural history and risk of rupture that must be weighed against an individual’s comorbidities, life expectancy, treatment-related risks and likelihood of treatment success. This report provides a comprehensive review of unruptured cerebral aneurysms in the elderly, with a special focus on the key challenges that this age group presents, including frailty, cognitive dysfunction, reduced life expectancy, vasculopathy and poor prognosis in case of rupture. These challenges determine the risk, benefit and likelihood of success of both surgical and endovascular treatments, drive innovative surgical techniques, and contribute to the trend in endovascular treatment in patients of advanced age. While coiling with or without adjunctive techniques or flow diversion will continue to increase, robust preclinical studies regarding the role in neuroinflammation in aneurysm development, growth and rupture represent potential future targets that may be particularly relevant to the elderly population. We anticipate that this review will provide a clinical framework for managing unruptured aneurysms in this challenging cohort, which will only enlarge with time as the population ages.


Many studies have reported that dietary fibers play a crucial role in promoting intestinal health of the host, since it strengthens functions of epithelial barrier and meanwhile maintains intestinal homeostasis of the host by modulating gut microbiota and short‐chain fatty acid (SCFA) production. Pig is a good animal model to study effects of dietary fiber on gut health and microbial community. This review has summarized the relevant knowledge available based on roles of various dietary fibers in gut health and energy metabolism of pigs and humans. Evidences summarized in our review indicated that modulating intestinal microbial composition and SCFA production by consuming specific dietary fibers properly could be conducive to health improvement and disease prevention of the host. However, types of dietary fiber from edible foods exert divergent impacts on gut health, energy metabolism, microbial composition, and SCFA production. Therefore, more attention should be focused on different responses of various dietary fibers intake on host metabolism and health. Modulating intestinal microbial composition and short‐chain fatty acid (SCFA) production by regulating specific dietary fibers intake properly could be conducive to host health improvement and disease prevention. Types of dietary fiber from edible foods exert divergent impacts on gut health, microbial composition, and SCFA production. More specifically, gut microbiota intensify integrity of the gut barrier comprised by intestinal epithelial cells, suppress colonization of enteric pathogens, and produce antibacterial peptides in the mucus layer of host intestine  to identify the specific mechanisms of SCFA produced from dietary fiber fermented by gut microbiota on functions of animal tissues and organs, (2) to clarify the relationship between host health and gut microbiota shaped by the dietary intervention with dietary fibers, (3) to further illustrate different responses of various dietary fibers derived from edible foods and their combinations on host health. Overall, we suggest that more attention should be focused on specific chemical constituents and physical characteristics of various dietary fibers when they take actions in regulating host metabolism and health.None of the authors had a financial or personal conflict of interest in relation to the present study.Pan Yang: Conceptualization (supporting); Data curation (supporting); Formal analysis (lead); Investigation (lead); Visualization (lead); Writing‐original draft (lead). Jinbiao Zhao: Conceptualization (lead); Data curation (lead); Formal analysis (supporting); Funding acquisition (lead); Project administration (lead); Writing‐review & editing (lead).Not applicable.All authors consent that raw data presented in this review are available after publication. Please contact author for data requests.


Theories of age and emotional wellbeing posit that older age is associated with better affective well-being through avoidance or minimization of distressing experiences and prioritizing positive experiences and emotions. To test these theories, researchers have examined change in affect  associated with negative interpersonal experiences in daily diary studies, given the compromising effects these interpersonal stressors exert on daily affect. In contrast, age differences in the potential affect-enhancing effects of positive interpersonal experiences have been comparatively neglected. Using the second wave of the National Study of Daily Experiences, we evaluated age differences in the frequency of daily negative and positive interpersonal interactions, as well as the affective responses to these interpersonal interactions. Positive and negative affect, as well as negative and positive interpersonal interactions were assessed on eight consecutive evenings. Analyses included 818 participants  who experienced both negative and positive interpersonal interactions during the 8-day protocol. Preliminary results revealed increased frequency of negative interpersonal interactions and decreased frequency of positive interpersonal interactions with age (ps<.01). Further, negative interpersonal interactions were associated with increases in negative affect and decreases in positive affect (ps<.01), while positive interpersonal interactions were associated only with increased positive affect (p<.01). Finally, modest evidence of age-related reductions in the affective impact of negative, but not positive, interpersonal interactions emerged (p=.03). Discussion will focus on how studies of interpersonal interactions in daily life can inform theories of aging and promote emotional wellbeing throughout adulthood and later life.


As the coronavirus disease 2019 (COVID-19) spread in the early days of the pandemic, governments neglected World Health Organization (WHO) guidance and imposed travel restrictions. These public health measures employed varied levels of restrictiveness at national borders, in some cases banning all travel between countries. Where these border control measures were undertaken for domestic political reasons, enacted without consideration of public health evidence, they divided the world when solidarity was needed most.With the emergence of the Omicron variant, national governments once again returned to international travel restrictions, posing challenges for the rule of law in global health governance. Future reforms of global health law must account for this continuing impulse to enact travel restrictions, ensuring that international legal obligations reflect evolving public health evidence.International Health Regulations, 2005 revision; IHR (2005) govern how countries address collective threats in global solidarity; yet international travel bans can drive countries apart through economic isolation, trade disruptions, discriminatory restrictions and rights violations.The In the early COVID-19 response, we remained concerned where national governments bypassed WHO’s public health recommendations in a rush to impose travel bans that targeted specific countries in ways that exacerbated political divisions, blocked essential goods and deflected from established mitigation measures – including travel advisories, diagnostic testing and quarantine policies.We continue to be concerned, however, that many governments are still reflexively deploying discriminatory travel restrictions to meet domestic political imperatives, prioritizing government action without sufficient justification in public health evidence. The latest round of travel restrictions, enacted in response to the Omicron variant, reveal the often-pernicious effects of such decision-making on low- and middle-income countries. When South Africa transparently reported a new variant of concern, countries immediately limited travel to and from South Africa, in some cases expansively targeting additional Southern African countries, without consideration of WHO guidance and despite updated evidence of variant spread well beyond the targeted countries.The mixed public health success of travel restrictions during the pandemic calls into question IHR (2005) obligations in the context of evolving public health knowledge.,In reforming global health law to reflect evolving public health knowledge, IHR (2005) revisions and pandemic treaty negotiations must provide flexibility in implementing evidence-based travel restrictions while strengthening WHO guidance to reflect epidemiologic data, facilitate health equity and support international cooperation.


The chemical diversity of natural products is established by an elegant network of biosynthetic machinery and controlled by a suite of intracellular and environmental cues. Advances in genomics, transcriptomics, and metabolomics have provided useful insight to understand how organisms respond to abiotic and biotic factors to adjust their chemical output; this has permitted researchers to begin asking bigger-picture questions regarding the ecological significance of these molecules to the producing organism and its community. Our lab is motivated by understanding how select microbes construct and manipulate bioactive molecules by utilizing vanadium-dependent haloperoxidase (VHPO) enzymology. This commentary will give perspective into our efforts to understand the unique VHPO-catalyzed conversions which modulate the activities within two ecologically relevant natural product families. Through enhancing our knowledge of microbial natural product biosynthesis, we can understand how and why these bioactive molecules are created. Natural products (NPs), also known as secondary or specialized metabolites, are composed of small organic molecules that have long been appreciated for their therapeutic potential . The marAs the tools of chemical ecology have matured, researchers have been able to ask more targeted questions about the factors that elicit NP production. With modern genomic, transcriptomic, and metabolomic profiling techniques, the field has started to reify links between secondary metabolite production and the specific internal state of a single organism while considering its surrounding community. The signal-molecule-based activation of silent NP BGCs has emphasized the role that the local microbiota plays in the elicitation of diverse community-modulating NPs , 10. OurStreptomyces and other bacteria site-specifically halogenate small molecules to elicit precise biosynthetic transformations (One of the many unique features of the marine biosphere is the relative abundance of vanadium and its subsequent utilization by microbial and macroalgal communities . In the rmations . We intermations .The most explored area of site-specific VHPO biosynthetic enzymology has involved the diverse naphthoquinone-based family of meroterpenoids. These mixed polyketide-terpene NPs are produced by marine and soil actinobacteria and exhibit a range of useful Gram-positive antibacterial, cytotoxic, and antifouling activities . DespiteStreptomyces NP biosynthesis but also within less established marine and terrestrial microbes.Of the THN-derived meroterpenoids, the napyradiomycins are uniquely well suited for hypothesizing “how-and-why” NPs are interconverted by VHPOs and other accessory enzymes in the marine biosphere. Over 50 unique napyradiomycins have been isolated, and new molecules continue to be discovered . Some ofPseudomonas species (Microbulbifer host species while increasing their toxicity toward other bacteria (Although less established than their roles in constructing endogenous NPs via biosynthetic routes, there is increasing evidence to suggest that VHPOs may modulate exogenous quorum sensing molecules. A macroalgal VHPO has been previously established to disrupt bacterial communication through homoserine lactone degradation and bromofuranone production to minimize surface fouling . The alk species . These m species . We are bacteria . This VHin vitro enzymology with ecologically relevant marine bacterial homologs. Pending the generalizability of this halogenation biochemistry, we aim to begin assessing the in vivo activities of these VHPOs in axenic cultures and within simulated communities alongside known AQ producers. Transcriptomic and metabolomic analyses using liquid coculturing experiments may provide insight into the role of VHPO-mediated AQ modification. Imaging mass spectrometry in combination with solid-phase coculturing conditions can additionally assess the spatial localization of quorum sensor production, interconversion, and microbial interactions. We envision that a rigorous understanding of AQ halogenation enzymology will enable us to target specific ecological questions regarding the significance of VHPOs in marine microbiology.We intend to initially investigate the impact of AQ-modulating VHPOs using In comparison to common terrestrial transition metals like iron, molybdenum, and zinc, the full extent of the biological and ecological roles that vanadium plays is less well understood , 12. Muc15–


Numerous microbial diversity surveys conducted over the past decade have attempted to link specific ASD biomarkers to gastrointestinal tract disturbances, but results generated across cohorts and studies remain inconsistent. This commentary discusses multidirectional interactions between the host, the microbiome, and external factors germane to autism. Recent studies posit the heritability of the gut microbiome itself, confounding attempts to discern heritable from nonheritable effectors in neurodevelopmental disorders. Elucidating the ever-evolving gut microbiome’s role in modulating the ASD phenotype will most certainly require new experimental methodologies and designs. In a recent paper published in  Elucidating the countless factors contributing to the etiology of autism is incredibly challenging. Upon entering this field “late” in my career, I was then, and remain today, awestruck at both how much and how little is known about this disorder. Over the past decade, even the very definitions of the core symptoms of autism spectrum disorder (ASD) have changed. Between 2010 and 2015, both the number of known cistrons associated with autism  whose unprecedented size would otherwise preclude meaningful study, and innovative techniques enabling the segregation of features of the host from those of its microbiome.Finally, the scientific community desperately needs to bolster the current understanding of the complex interplay between genetic-driven and heavily microbiome-influenced systems. Within this vein, we must explore whether exposure to detrimental environmental factors early in life coupled with innate genetic susceptibility might impair brain development. Addressing such questions will require novel experimental design frameworks, emerging analytical tools capable of leveraging data sets (both preexisting publicly available data sets and


This symposium brings together four papers that address racial health disparities by investigating stressful aspects of social relations at different points in the life course. Cleary and colleagues focus on racial disparities in psychological health by testing cross-sectional effects of intergenerational stress over time. In particular, they investigate effects of network composition on the relationship between mothers' stressors and their children's depressive symptoms at three time points over 23 years. Camacho and colleagues use longitudinal data from the National Social Life, Health and Aging Project to examine cognitive decline among U.S. African-American, Latino, and White adults aged 60 and above. Results indicate loneliness predicted greater global cognitive decline over time in all groups. However, race differences in this association were found across cognitive function domains. Turner and colleagues consider dementia caregiving challenges among non-Hispanic Blacks. Data from five focus groups were analyzed to reveal distinctive challenges to caregiver health during the COVID-19 pandemic including increased burden and barriers to service access. Finally, Sol and colleagues examined the bidirectional association between loneliness and self-rated health over time among a racially diverse sample. Findings illustrate racial patterns in how loneliness at midlife influences health in later life. Antonucci will discuss the role of stress from social relations as a means to fully understand racial disparities in health across the life course.


Plant genebanks provide genetic resources for breeding and research programs worldwide. These programs benefit from having access to high-quality, standardized phenotypic and genotypic data. Technological advances have made it possible to collect phenomic and genomic data for genebank collections, which, with the appropriate analytical tools, can directly inform breeding programs. We discuss the importance of considering genebank accession homogeneity and heterogeneity in data collection and documentation. Citing specific examples, we describe how well-documented genomic and phenomic data have met or could meet the needs of plant genetic resource managers and users. We explore future opportunities that may emerge from improved documentation and data integration among plant genetic resource information systems. Genebanks offer a broad range of plant genetic diversity for use in research and breeding programs. For decades, crop researchers have collected phenotypic trait data on genebank accessions. New high-throughput technologies facilitate the collection of phenomic data . Similarly, smaller-scale DNA marker data have been eclipsed by more comprehensive genomic data for characterizing collection genetic diversity. With these large datasets, the challenges of digital information management are becoming as important as managing the physical collection of germplasm. Databases that integrate data types, promote standardized data collection and documentation methods, incorporate appropriate analytical tools and provide user-friendly access will help curators and users of plant genetic resources (PGR) to manage, locate and identify diversity of agronomic and horticultural importance . TanksleTriticum aestivum L.] variety ‘Jagger’ and maize [Zea mays L.] inbred line ‘B73′). An example of homozygous/heterogeneous accessions are landraces of self-pollinating crops that are comprised of an assortment of different genotypes. Heterozygous/homogeneous accessions include clonally maintained but originally outcrossing crops . Heterozygous/heterogeneous accessions are represented by wild species accessions and outcrossing landraces. As wild species accessions are regenerated, the extent of heterozygosity may decrease  [Cicer arietinum L.] [Genome-wide association analysis has enabled PGR to contribute more extensively to marker/gene discovery in most species. Diversity subsets from genebank collections are a readily available resource to perform GWAS using a range of markers from simple sequence repeats (SSRs) to SNPs from GBS or SNP arrays . Whole-gtiva L.] ; soybean) Merr.] ; chickpeinum L.] ) and perinum L.] . GWAS isPlant breeders and researchers require an understanding of the phenotypic/phenomic data that are available. This includes documentation about how the data were collected, such as the numbers of individuals sampled and experimental field designs (particularly for heterogeneous accessions), as well as the use of standardized descriptors and ontologies. Most of the traits important to breeders exhibit significant genotype × environment interactions so the full environmental context under which phenotypic measurements were made is necessary ,48. HighPisum sativum L., and many fruits. However, pea and other new crop ontologies are under development. Other harmonious crop ontologies can be found on Planteome [Beginning in the 1990s, an evolution occurred from simple, formal phenotypic descriptors to the machine-readable ontologies available today, wherein the controlled vocabulary includes not only trait definitions but also relationship terms, so that complex phenotypic information can be processed by computer. Phenotypic descriptors for PGR have been published for over 100 crops under the auspices of the CGIAR centers IPGRI and Bioversity International . Bioversity used these to develop crop ontologies and the Crop Ontology Curation Tool . These olanteome  and Agrolanteome . The goalanteome . As geneHigh-quality genebank collections contain well-curated passport, phenotypic, and genotypic data. Acquiring these data is challenging due to resource limitations and the vast size of most genebank collections. Success depends upon partnerships between genebanks and user communities. As they become available, genomic and phenomic data can help guide collection management and improve the value of the collection. These data permit the identification of collection gaps, which can be filled with new acquisitions . They alGenomic and phenomic data can provide knowledge applicable to curation, such as whether accessions are correctly assigned to taxon, whether they are redundant, or whether they differ when they should not . They caLens species and Lens culinaris Medik. sub-species, are difficult for non-taxonomists to identify. Wong et al. [Availability of accession-level genomic data for genebank collections has facilitated taxonomic identification of unusual or hybrid species. Lentils, which include g et al.  used seqGenotyping the maize Ames Panel revealed several interesting findings related to curation . First, Hordeum vulgare subsp. spontaneum C. Koch.) collection” [Solanum tuberosum L.) accessions with a 12K SNP array and identified putative misclassified accessions [Lactuca sativa L.) PGR in the USDA collection lack genetic diversity, hindering genetic advances in this important crop [Genomic data have provided useful information about genetic gaps in collections. Previously, geographic coverage was the primary criterion for targeting plant acquisitions and assembling core collections. Correlation of geographic gap-filling and genomic gap-filling has shown the advantage of using genomic data. The IPK genebank analyzed GBS data for 21,405 barley accessions to identify gaps in the collection. They found “a pronounced under-representation of some regions of the world in IPK’s wild barley  offer numerous visualizations and capabilities connected to genebank accessions. Maize SNP data were used to establish an IBS relationship matrix among 2800 inbred lines, and this matrix was used to populate a tool called “TYPSimSelector” ,97, wherLooking forward, data curation will likely involve the use of persistent identifiers (PIDs) such as Plant Introduction (PI) numbers or Digital Object Identifiers (DOI) for sample identification. Through the adoption of BrAPI, the GRIN-Global information management system can become interoperable with Breeding Insight and crop-specific databases. Several databases, including Bridge IPK  and GermCurrent and future genebank users, as well as curation teams, will increasingly require access to high-quality genomic and phenomic data. Access to genetic diversity information could help ensure phenotypic data are collected from an adequate number of individuals. Integration of genomic and phenomic data for heterogeneous accessions requires special attention to DNA polymorphism and elevated or complex patterns of phenotypic variance. Technological advances in information management systems have focused primarily on specific crops. Future efforts should consider the relative heterogeneity of genebank accessions and how it can be effectively managed when data are collected. Systems must be user-friendly and widely applicable to diverse customers. In addition, they must be adaptable and scalable, to support new genomic and phenomic technologies. Future research should focus on ensuring that tools are available to effectively use genomic and phenomic data for informed curation decisions.Sorghum bicolor (L.) Moench) demonstrated the power of this approach for selecting accessions for high biomass from a large PGR collection [Increasingly sophisticated artificial intelligence methods and sequence data lead to the question of whether every accession must be phenotyped to choose accessions for gene(s) or trait(s) of interest. Advances in statistical prediction may change how characterization data can select germplasm for further evaluation. FIGS (Focused Identification of Germplasm Strategy) applies machine learning (ML) algorithms and environmental data to identify candidate accessions associated with a trait of interest . In Barillection . Improvellection ,107.


Arteriogenesis is one of the primary physiological means by which the circulatory collateral system restores blood flow after significant arterial occlusion in peripheral arterial disease patients. Vascular smooth muscle cells (VSMCs) are the predominant cell type in collateral arteries and respond to altered blood flow and inflammatory conditions after an arterial occlusion by switching their phenotype between quiescent contractile and proliferative synthetic states. Maintaining the contractile state of VSMC is required for collateral vascular function to regulate blood vessel tone and blood flow during arteriogenesis, whereas synthetic SMCs are crucial in the growth and remodeling of the collateral media layer to establish more stable conduit arteries. Timely VSMC phenotype switching requires a set of coordinated actions of molecular and cellular mediators to result in an expansive remodeling of collaterals that restores the blood flow effectively into downstream ischemic tissues. This review overviews the role of VSMC phenotypic switching in the physiological arteriogenesis process and how the VSMC phenotype is affected by the primary triggers of arteriogenesis such as blood flow hemodynamic forces and inflammation. Better understanding the role of VSMC phenotype switching during arteriogenesis can identify novel therapeutic strategies to enhance revascularization in peripheral arterial disease. In peripheral arterial disease (PAD), atherosclerosis limits blood flow to the lower extremities and represents approximately 25% of the global burden of cardiovascular disease and 1.7% of the overall global burden of disease . The curThe endogenous revascularization after ischemic insult involves multiple biological processes including vasculogenesis, angiogenesis, and arteriogenesis. While vasculogenesis occurs mainly during embryonic life, experimental evidence has shown that vasculogenesis contributes to adult neovascularization at least to repair the damaged capillary networks. In vasculogenesis, blood vessels form de novo via the differentiation of progenitor vascular cells into discrete vascular cells such as endothelial cells ,11, smooNevertheless, most of our knowledge about the pathophysiology of arteriogenesis is based on experimental animal studies of arterial occlusion. The terms collateralization and arterialization are often confused with arteriogenesis and are poorly defined . This reWhen a primary arterial trunk is occluded, it leads to a pressure drop downstream of the arterial network subsequently creating a pressure gradient across pre-existing collateral circulation and forcing the diversion of blood flow through the collaterals. The altered blood flow generates hemodynamic forces in collateral arterioles and arteries triggering two vascular responses: short-term vasodilation and long-term expansive vascular remodeling . The shoSynthetic smooth muscle cells migrate from the media to the subendothelial space (intima) where they proliferate abundantly and produce ECM components including collagen, elastin, and proteoglycans to the subintimal space resulting in the formation of a new layer of SMC . At thisUpon successful arteriogenesis, the collaterals exhibit an extensive outward and hypertrophic remodeling, which is associated with the transformation of a small microvascular resistance vessel into a large conductance artery . The smoVascular smooth muscle cells in the adult vasculature are not terminally differentiated cells. They possess extensive plasticity such that it can be stimulated to undergo a structural and functional transition into proliferative/migratory/synthetic phenotype or undergo an extreme phenotypic change into osteochondrocyte-like cells , foam-liThe mature contractile phenotype of SMCs is morphologically characterized by low numbers of protein synthesis organelles, e.g., rough endoplasmic reticulum, Golgi apparatus, or free ribosomes . They deThe molecular basis of sustaining the SMC contractile state has been explained by maintaining CArG–SRF–Myocardin complex . Any heaSeveral pathways transduce signals from cell surface receptors or integrins in response to the surrounding environmental factors to maintain the contractile phenotype. The RhoA/ROCK signaling triggers actin polymerization increases post-translational modification of MRTFs and releases it to the nucleus to induce contractile gene expression . TGFβ enThe loss of the contractile phenotype occurs via growth factors such as Platelet-derived growth factor-BB (PDGF-BB), FGF, and EGF that activate MAPK cascade via the Ras/Raf/MEK/ERK pathway. The MAPK activation can phosphorylate and activate TCF proteins such as Elk-1 to displace MYOCD or induce SRF-dependent transcription of early response growth, dedifferentiation genes, and repression of smooth muscle contractile genes . ERK canUpon arterial occlusion, the increase of blood flow and intravascular pressure in the bypass collaterals can generate two primary forces: fluid shear stress and circumferential wall tension . The fluIn contrast, after arterial occlusion, early vasodilation of collaterals leads to a rapid decrease in the intra-luminal pressure. Thus, according to Laplace’s formula, we expect that the circumferential wall stress would not change significantly in the early stage. In addition, the diminished blood pressure in downstream vessels is much lower than the proximal arterial pressure; thus, this pressure is unlikely to cause a significant stretch force on medial SMC at this phase. Indeed, the SMC in small arteries and arterioles generally react to the acute rise of intraluminal pressure by contraction (myogenic response) to regulate the tissue blood flow ,90. HoweThe increase in fluid shear stress force is transmitted to the SMC by diffusible molecules such as nitric oxide (NO) . NO is sMost collaterals tend to be tortuous small arteries . The steEndothelial surface glycocalyx and its components can act as a mechanoreceptor and can transmit mechanical stimuli to the cytoskeleton, which can then activate downstream signaling pathways such as PI3K/AKT/eNOS and NFκB . The plaIn contrast, the alterations in the intraluminal pressure in the later stages of arteriogenesis can be extended to exert a mechanical force on the cellular components of VSMCs, which act as a mechanosensor to initiate subsequent signal transduction events . Medial Additionally, activation of integrin receptors, stretch-activated cation channels, and G proteins are also observed in SMC membranes of collateral vessels in response to stretch forces . These fCyclic stretching is a critical inducer of MCP-1 expression in SMC of remodeling collaterals . It goveThe arterial wall strain is chronically elevated in systemic hypertension conditions. The small arteries and arterioles remodel inwardly through a eutrophic process of rearrangement of the same SMC around a smaller lumen . ConversThe initial phase of collateral vasodilation is driven by fluid shear stress and occurs within the early stage of post-occlusion. However, this vessel enlargement accounts for a small proportion of final vessel expansion, and it slows following shear stress normalization . The appEndothelial cells in pre-existing collaterals are the first effectors to initialize an inflammatory process following arterial occlusion . In resphighCCR2highCX3 CR1low) and tissue repair (Ly6 ClowCCR2lowCX3 CR1high) in mouse [high) are detected mainly in the collaterals during the early phase of arteriogenesis whereas the anti-inflammatory monocytes (Ly6 Clow) predominate the collaterals during the growth and expansion phase of arteriogenesis [high monocytes are more likely to differentiate into M1 macrophages, which secrete various pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-12, and TNFα. They exhibit high proteolytic activity [low monocytes may differentiate into M2 macrophages, which secrete anti-inflammatory cytokines such as IL-10 and TGFβ1 and express growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), thus promoting collateral remodeling and expansion [Medial SMCs also contributes to initiating or amplifying stretch-induced inflammation in collateral remodeling . They prin mouse . The infogenesis . Ly6 Chiactivity . In contxpansion . Many ofxpansion ,145,146.xpansion . Other fxpansion ,149.Monocytes and macrophages are an important source of metalloproteinases and other proteases such as cathepsins during vascular repair process . During Other inflammatory cell populations have been reported to infiltrate the collateral sites during arteriogenesis, e.g., neutrophils , mast ceArteriogenesis is a physiological remodeling response of the collateral arteries in the occlusive arterial diseases. Despite the dramatic outward remodeling of collaterals, blood flow is restored only up to 40–50% of the unblocked artery without intervention. One reason for the limited restoration of blood flow is the premature normalization of fluid shear stress (primary trigger of arteriogenesis). This natural compensatory capacity is diminished even further in subjects with co-morbid diseases such as diabetes . Using aVascular smooth muscle cells play a central role during arteriogenesis due to their plasticity. Phenotypic switching of the contractile VSMC to a synthetic state is a critical cellular event that sustains the growth and outward remodeling of collaterals. In contrast, VSMC re-differentiation back to their contractile state is important to regain vascular functions and prevent inappropriate hypertrophic remodeling of collaterals that could perturb the blood flow for distal ischemic tissues. The physiological normalization of fluid shear can lead to a premature switch of synthetic VSMC to a contractile quiescent phenotype; this switch eventually attenuates the collateral wall growth and remodeling. It has been shown that growth factor therapy can stimulate angiogenesis and also is able to stimulate arteriogenesis ,163. ManTargeting vascular smooth muscle cell phenotype switching has been suggested to be a therapeutic approach for tackling other vascular diseases such as atherosclerosis and hypertension. However, since the dynamics of VSMC phenotype switching are different in arteriogenesis, the timing of intervention would be challenging to achieve effective therapy. Another challenge of targeting VSMC in arteriogenesis is that several cellular events of atherosclerotic plaque development are also involved in arteriogenesis. For instance, extracellular matrix degradation, VSMC migration, and proliferation are activated in both arteriogenesis and atherogenesis. The stimulation of arteriogenesis through agents that promote VSMC proliferation or positive arterial remodeling could have side effects on the aggravation of atherosclerotic plaques in PAD patients who typically suffer from atherosclerosis. While many experimental studies have been conducted to investigate the molecular mechanisms of VSMC phenotype regulation in the context of atherosclerosis, the molecular mechanisms of VSMC phenotype switching that specifically control arteriogenesis in ischemic vascular disease remain largely unknown. Previous studies have been carried out to trace the VSMC phenotype dynamics in vascular repair and atherosclerosis models. Further studies are required for VSMC lineage tracing studies during arteriogenesis. These can help to identify novel specific molecular targets for therapeutic arteriogenesis of peripheral arterial disease patients.


Heritability of cognitive ability changes across late adulthood, although whether genetic variance increases or decreases in importance is not understood well. We performed a systematic review of the heritability of cognitive ability derived from longitudinal twin studies of middle-aged and older adult twins. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles were identified in APA PsycINFO and Clarivate Web of Science electronic databases. Identified articles were screened by title and abstract; remaining full-text articles were then fully evaluated. Reference sections served as an additional method for identification of relevant articles. In total, 3,106 articles were identified and screened, 28 of which were included and were based on data from 10 longitudinal twin studies published from 1994-2021. There are large genetic influences on an initial level of cognitive performance across domains whereas there are small to moderate genetic influences on change in performance with age. Evidence was less definitive about whether the same or different genetic factors contribute to both level and change. Non-shared environmental influences appeared to drive individual changes in cognitive performance. Heritability tended to either be stable or decline after 65 years, possibly because of the increasing importance of non-shared environmental influences on cognitive ability. Recent studies report increases in heritability across specific subtests and domains. Shared environmental variance accounted for little variance in cognitive ability. Emerging research questions and future directions for understanding genetic and environment influences in the context of gene-environment interplay are highlighted in this review.


Glutathione is an intracellular antioxidant that neutralizes reactive oxygen species and prevents tissue damage. Dietary supplementation with the glutathione precursors glycine and n-acetylcysteine supports the maintenance of normal glutathione levels in several age-related diseases, but the optimal doses and their efficacy in healthy elderly are not established. We report results from a randomized controlled clinical trial in 114 healthy volunteers (mean age = 65 years) receiving glycine and n-acetylcysteine (GlyNAC) at three different doses for two weeks . Older subjects showed increased oxidative damage and a lower reduced-to-oxidized glutathione ratio (GSH:GSSG) compared to young subjects, but unchanged total glutathione levels. GlyNAC did not increase levels of circulating glutathione compared to placebo treatment, the primary study endpoint. However, stratification analyses suggest that subjects with high oxidative stress and low glutathione status responded with glutathione generation. We find that unrelated to glutathione status, healthy aging was associated with lower levels of fasting glycine that can be increased towards those observed in young subjects with supplementation. Using preclinical models, we find that tissue glycine depletion is a common feature of healthy aging. Supplementation of old mice with glycine efficiently improved age-related decline of mitochondrial respiratory function in skeletal muscle and prevented a gene program associated with protein catabolism observed in control-treated animals. In conclusion, GlyNAC is safe and well-tolerated and may selectively increase glutathione levels in older subjects with oxidative stress and glutathione demand. Our data further suggest that glycine may support mitochondrial function independently of NAC.


Practitioners frequently tailor programming to meet participant characteristics and logistic constraints, or to incorporate diverse participants, such as intergenerational programming. Adapted programming may be responsive but reduce impact on outcomes. With growing interest in and limited availability of intergenerational protocol, implementation science guides program tailoring to ensure that youth and older adults mutually benefit from adapted programming. We integrated guidelines for tailoring interventions (Framework for Reporting Adaptations and Modifications-Expanded: FRAME) and evidence-based intergenerational practice. We illustrate how program fidelity can be supported in intergenerational settings using examples from an adapted USDA-approved preschool nutrition curriculum delivered intergenerationally. Program acceptability, appropriateness, and feasibility were rated favorably by program stakeholders, and observational implementation data suggest fidelity can be maintained using evidence-based intergenerational strategies. Our findings support the potential for protocol developed for one age group to benefit youth and older adults when it is adapted using implementation and intergenerational guidelines.


Are eusociality and extraordinary aging polyphenisms evolutionarily coupled? The remarkable disparity in longevity between social insect queens and sterile workers—decades vs. months, respectively—has long been recognized. In mammals, the lifespan of eusocial naked mole rats is extremely long—roughly 10 times greater than that of mice. Is this robustness to senescence associated with social evolution and shared mechanisms of developmental timing, neuroprotection, antioxidant defenses, and neurophysiology? Focusing on brain senescence, we examine correlates and consequences of aging across two divergent eusocial clades and how they differ from solitary taxa. Chronological age and physiological indicators of neural deterioration, including DNA damage or cell death, appear to be decoupled in eusocial insects. In some species, brain cell death does not increase with worker age and DNA damage occurs at similar rates between queens and workers. In comparison, naked mole rats exhibit characteristics of neonatal mice such as protracted development that may offer protection from aging and environmental stressors. Antioxidant defenses appear to be regulated differently across taxa, suggesting independent adaptations to life history and environment. Eusocial insects and naked mole rats appear to have evolved different mechanisms that lead to similar senescence-resistant phenotypes. Careful selection of comparison taxa and further exploration of the role of metabolism in aging can reveal mechanisms that preserve brain functionality and physiological resilience in eusocial species. Eusocial animals, characterized by reproductive division of labor, cooperative brood care, and overlap of generations, can have extraordinary lifespans. Eusocial hymenopteran  queens may live 100 times longer than solitary insects. In some eusocial species there is a similar lifespan differential between queens and workers . Naked mHarpagnathos salatator, workers can facultatively become reproductive upon queen loss  declines with age (superoxide dismutase (SOD), lowers levels of protein carbonylation (a measure of oxidative damage) and extends lifespan  store sperm from a single insemination for life, allowing sperm counts to reliably estimate queen age . Queens Caste theory  can be aMost aging comparisons with NMRs involve studies of other taxa. Mutant dwarf mice with growth hormone mutations exhibit pedomorphic traits and have at least 50% longer lifespans than wild-type mice, and fewer aging-associated diseases . ExperimReticulitermes speratus reproduce in hypoxic, hypercapnic chambers, conditions that enhance their reproductive output (Harpegnathos saltator (Brain metabolism is little explored in eusocial and solitary species . Is enere output , althouge output . Future saltator  hint at saltator  will allEusocial insects and eusocial mammals share aging phenotypes despite phylogenetic divergence, but different mechanisms appear to have evolved to facilitate delayed aging in their nervous systems. The striking difference in worker and reproductive lifespan in eusocial insects is less pronounced in NMRs, further suggesting the evolution of multiple pathways to achieve long and healthy lifespans in eusocial taxa. To enable precise comparisons between vertebrate and invertebrate taxa, similar methodologies, such as quantifying levels of homologous biochemical markers of aging or comparisons among divergent taxa must be applied. Integration of theories of aging and development in eusocial and solitary species will enhance our understanding of how social organization shapes aging phenotypes and mechanisms that promote longevity.YG, MM, and JT wrote the manuscript. YG and JT provided the funding. All authors contributed to the article and approved the submitted version.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.


Lack of insurance or funds for dental services, lack of access to dental offices, fear of dentists, and avoidance of dental offices during COVID can lead to oral health problems in older adults. Brushing, flossing, and drinking fluoridated water can protect teeth when dentists are unavailable. Limiting intake frequency of carbohydrates and chewing sugarfree gum after eating add protection. A recent systematic review and meta-analysis confirmed the effectiveness of sugarfree gum in reducing caries, in children and adults who chewed sugarfree gum compared with those who did not chew. Chewing sugarfree gum significantly reduced caries increment, with a prevented fraction of 28 percent, roughly equivalent to the prevented fractions for fluoride toothpastes and supplements. A follow-up systematic review provides further evidence that chewing sugarfree gum reduces the numbers of Streptococcus mutans in the oral cavity. Finally, chewing sugarfree gum could alleviate symptoms of xerostomia and may reduce caries.


Manis javanica) achieved notoriety during the Coronavirus disease pandemic because of flawed evidence suggesting that pangolins could be intermediate hosts . Native to Java (thus javanica), their habitat includes Southeast Asia, especially the Indomalayan archipelago and Sunda Islands. Humans hunt pangolins for their meat, consume their blood as an elixir, and use their scales and other body parts as ingredients for crafting leather products and nonefficacious medications. Linnaeus named the genus


The search for novel prostate cancer biomarkers is one of the major topics in recent urologic research. Given the still unsatisfactory performance of the available diagnostic biomarkers in the detection of significant prostate cancer cases and the lack of prognostic and predictive biomarkers with high specificity, there is still an urgent need for new biomarkers. This special issue presents nine original research papers and two reviews elucidating novel developments in prostate cancer biomarkers. Interestingly, two major topics were in focus, microRNAs (miRNAs) as biomarkers ,2,3,4 anThe fast-growing field of miRNA biomarkers in liquid biopsies reflects the high expectations raised in the implementation of miRNA diagnostics. Fredsøe and colleagues analyzed 92 circulating miRNAs in plasma samples of 753 patients and found distinct regulation of miRNAs in patients with benign prostatic hyperplasia (BPH), localized prostate cancer, and advanced prostate cancer with large overlaps between the groups [Using urine and urinary cells, respectively, is the second major approach in minimally invasive liquid biopsies for PCa detection. Borkowetz and colleagues used urinary sediments to analyze a 12-miRNA panel by qPCR [Successful implementation in routine clinical use requires standardization of miRNA measurements. Konoshenko and coworkers evaluated the diagnostic potential of ratios constructed from a panel of 12 cell-free miRNAs, using urine extracellular vesicles, clarified urine, and plasma. Eight miRNAs combined into six ratios showed maximum stability and 97.5% accuracy in separating PCa patients from the control group  . In a seBlood and urine are also profitable sources of metabolites, which have recently been used in numerous disease states. Yang and colleagues conducted a study searching for urine metabolite biomarkers for the detection of PCa. They found twenty differentially expressed urine metabolites in a cohort of 50 prostate cancer patients compared to non-cancerous individuals . The comWhile liquid biopsies are an upcoming promising tool of non-invasive PCa diagnostics, verification of biomarkers in tissues is mandatory to prove PCa being the primary cause of the alterations in liquid biopsy biomarkers. Latosinska and colleagues present a proteomic study comparing the proteome of PCa tissue with benign prostatic hyperplasia (BPH), a common co-morbidity especially in aged patients . They dePatients with GS ≤ 6, i.e., at low risk, are eligible for active surveillance. Yu and colleagues asked whether multiparametric MRI (mpMRI) can be a substitute or supplement of traditional tools as PSA, digital rectal examination, and transrectal ultrasound-guided biopsy (TRUS) . They reTwo papers in this special issue elucidate oxidative stress related enzymes and peptides as potential biomarkers in PCa. As shown by Veljković and colleagues, xanthine oxidase (XO) activity was significantly higher in tumor tissue compared to heathy controls and strongly correlated with serum PSA levels . The autFinally, two reviews provide updates on prognostic and predictive omics-derived biomarkers for therapy of advanced PCa and especially of serum biomarkers in metastatic disease ,11. In tSaxby and colleagues focused on serum biomarkers , which can be used in conjunction with PSA as prognostic or predictive biomarkers for metastatic PCa. Forty-three were analyzed and revealed numerous biomarkers with potential value for identifying patients with advanced PCa and of value for the development of targeted treatment strategies. However, while basic data are available, clinical validation in prospective trials is urgently needed to bring them to routine use in clinical practice.This special issue elucidates some important aspects of PCa biomarker development and their potential clinical benefit and highlights advanced techniques of biomarker discovery. The future of those biomarkers strongly depends on prospective multicenter clinical diagnostic studies, which hopefully will find the support of the major funding agencies.


Daily oral pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV when used as directed among men who have sex with men (MSM). However, challenges with uptake and adherence to daily oral PrEP have prompted the development of new modes of administration, including a long-acting, intramuscular injectable. We sought to explore the treatment characteristics that may influence the willingness and uptake of long-acting injectable PrEP as opposed to the daily pills among a racially diverse sample of MSM.Between January and May 2021, we actively recruited 28 HIV-negative MSM  who lived in Philadelphia, PA during the past 12 months using social networking sites  and a community listserv. Qualitative data collection used a hybrid approach in which 4 focus groups and 10 semi-structured interviews were conducted virtually. Focus groups were kept racially and ethnically homogenous to identify differences in emerging themes related to PrEP willingness and preferences for specific prevention modalities.Participants discussed differing levels of interest and willingness to use long-acting injectable PrEP as opposed to the daily pills. The main perceived facilitator for injectable PrEP included convenience of use such as having fewer concerns with adhering to daily pills. Perceived barriers to injectable PrEP included (1) a dislike of needles as well as (2) concerns of potential side effects and (3) lower treatment efficacy . While Black and Latinx MSM reported experiences of racism and discrimination within the healthcare system, they also reported greater willingness to consider intramuscular injectables if their healthcare providers would provide in-depth information about the risks and benefits of this new modality. Our findings provide important guidance for the development and promotion of future strategies to enhance the uptake of long-acting injectable PrEP to address the HIV epidemic among MSM. Primary care providers should play a key role in ameliorating concerns related to hesitancy towards injectable PrEP, including emphasizing ease of dosing, effectiveness, and safety of long-acting PrEP to prevent infection.All Authors: No reported disclosures


Supportive marital relationships may reduce partners’ problematic health behaviors, whereas unhappy relationships may lack efficacious spousal monitoring of health and increase the likelihood of using maladaptive coping strategies, such as heavy alcohol use, to deal with relationship problems. We used pooled data from the 2014 and 2016 waves of the Health and Retirement Study to examine how both partners’ perceptions of marital quality were associated with heavy drinking. Our analytic sample included married couples in which both spouses were over age 50, completed the leave-behind psychosocial questionnaire, and provided non-missing data on marital quality and alcohol use . Measures included both positive and negative dimensions of marital quality and controls for sociodemographic, economic, health, household and marital characteristics. Using Proc Glimmix, we estimated a dual-intercept Actor-Partner Interdependence Model (APIM), in which separate equations were computed simultaneously for husbands and wives. For husbands, higher negative marital quality was associated with an increase in the odds of their own heavy drinking (OR=1.27), but there was no significant association between wives’ marital quality and husbands’ heavy drinking behavior. For wives, marital quality was not significantly associated with their own heavy drinking, but husbands’ higher ratings of both negative and positive marital quality increased the risk of wives’ heavy drinking . Results suggest that marital quality is associated with heavy drinking in later life: self-ratings of marital quality matter for men, whereas spousal perceptions of marital quality are more important for women.


Pre-pandemic, evidence existed that intergenerational service-learning programs support knowledge of aging and positive attitudes and perceptions . As spring 2020 COVID-19 lock downs and public health warnings urged physical distancing of community dwelling older adults, growing concern about the unintended consequences of increased social isolation on mental and physical health prompted the Secretary’s Office of Pennsylvania Department of Aging to design a pilot project with university faculty for virtual intergenerational social interaction. The Department identified older adults at the highest risk for social isolation . The resulting pilot project is fully integrated as a high impact practice into eight sections of recreational therapy and gerontology courses with participation by 210 undergraduate students and 210 older adults for 9 weeks of both the fall and spring semesters. Students, who received extensive classroom instruction aimed at avoiding negative stereotypes of older adults as helpless and dependent, called their assigned partner several times a week for at least an hour of communication. Using the UCLA loneliness scale, community-dwelling older adults reported frustration with isolation due to the pandemic. Those with low and moderate loneliness reported positive feelings about program and looking forward to interactions with students. Students gained virtual communication skills that may contribute to telehealth competencies, intervention skills such as assessment, life review/reminiscence, mindfulness techniques, and leisure education. Moreover, an analysis of student reflections revealed positive changes in attitudes toward older adults and the ability to enjoy common interests despite age differences.


OBJECTIVES/GOALS: Pancreatic cysts are comprised of both precancerous mucinous lesions and non-mucinous lesions with minimal malignant potential. Our goal is to improve our ability to classify the type of cyst using a combination of novel radiomic features and cyst fluid proteolytic activity. METHODS/STUDY POPULATION: Preoperative pancreatic protocol CT images from 30 patients with proteolytic assay characterization, followed by surgical resection with a pathologically confirmed pancreatic cyst diagnosis between 2016-2019 will be used in this study. We will contour images using the widely available software 3D Slicer, and extract radiomic features using IBEX software. We will analyze area under the ROC curves to identify the radiomic features that best differentiate mucinous from non-mucinous cysts, and identify features to be cross validated. The predictive ability of identified radiomic features combined with proteolytic assay will be determined by performing multiple logistic regression analysis and comparing AUROC analysis. We will determine sensitivity and specificity for individual, as well as combinations of, analytes to determine the optimal classifier. RESULTS/ANTICIPATED RESULTS: We anticipate that the predictive ability, sensitivity, and specificity of utilizing radiomic features combined with proteolytic assay data will exceed the performance of any individual test. DISCUSSION/SIGNIFICANCE OF IMPACT: This work is designed to provide a predictive radiomic model that will enable us to better identify mucinous cysts that require further evaluation, and potentially prevent unnecessary surgery in other patients. Ultimately, we would like to improve the accuracy of noninvasive radiographic evaluation using radiomic markers. CONFLICT OF INTEREST DESCRIPTION: Dr. Charles Craik is a co-founder of Alaunus Biosciences, Inc.


Black adults and women are more likely to experience serious cognitive decline in older age than their white and male counterparts. Evidence suggests perceived discrimination is associated with poor cognition in older adults, though the mechanisms remain unclear. Perceived discrimination has been linked to elevated inflammatory markers, such as C-reactive protein (CRP), which increases risk for worse cognitive functioning. Yet, little research has investigated whether CRP is implicated in the association between discrimination and cognition among Black older adults or if this relationship differs by gender. Using 2006-2016 data from Black adults ≥65 years old(N=1343) in the nationally representative Health and Retirement Study, random effects linear regression models (1) tested the association between discrimination and cognitive functioning; (2) explored whether this relationship differed for women and men; and (3) assessed whether elevated CRP mediated the association between discrimination and cognitive functioning. More frequent discrimination was associated with worse cognitive functioning , though gender did not moderate this relationship. Elevated CRP was significantly associated with worse cognitive functioning . Discrimination remained statistically significant in this model, indicating no mediation by CRP. Of note, inclusion of depressive symptoms and cardiometabolic conditions accounted for the association between both discrimination and CRP with cognitive functioning. These findings demonstrate the need for more within-group research on older Black adults documenting the complex relationship between discrimination, inflammation, and cognitive health. This approach will provide greater understanding of the biopsychosocial mechanisms underlying disparities in cognitive functioning in Black adults.


Between the years 1999-2008, a substantial increase in nursing home use occurred among Black and Latinx older adults, while white older adults’ use of nursing homes decreased. These disparate trends suggested potential racial and ethnic disparities in options for preferred long-term services and supports (LTSS) settings. Over the last decade, several initiatives have been put in place to support LTSS needs in the community. However, it is unclear whether Black and Latinx older adults are continuing to use nursing home services at disproportionate rates. We used LTCfocus data for 2011-2017 to explore current trends in nursing home use and access among Black and Latinx older adults in light of these current initiatives. Our findings reveal a continued rise in Black and Latinx older adults’ use of nursing homes while white older adults’ use continues to decline. More notably, there has been a decline in nursing homes servicing these minority groups.


ATP channels may provide analgesia and attenuate opioid tolerance and withdrawal OBJECTIVES/GOALS: Our long term goal is to develop therapeutics for the treatment of the overuse of opioids. The objective of this application is to test novel KATP channel-targeting prodrugs in rodent models of neuropathic and inflammatory pain in addition to opioid tolerance after chronic morphine administration. METHODS/STUDY POPULATION: In one study, two different measures for chronic pain were implemented in mice. Male and female mice (n=10) were subjected to spinal nerve ligation (SNL) or intraplantar injection of Complete Freund’s Adjuvant (CFA) to induce neuropathic and inflammatory pain, respectively. Administration of KATP channel prodrugs  attenuated mechanical hypersensitivity after SNL or CFA compared to vehicle . In a separate study, changes in mechanical hypersensitivity were tested while mice undergo chronic morphine treatment  with administration of the prodrugs. Tolerance was measured as the loss of antinociception, and withdrawal is measured ˜24 hours after the final morphine injection. RESULTS/ANTICIPATED RESULTS: Intrathecal administration of either KATP channel prodrugs significantly attenuated mechanical hypersensitivity after SNL and significantly attenuated mechanical hypersensitivity after CFA in mice. We predict that intrathecal administration of these prodrugs will also attenuate morphine tolerance and withdrawal in mice. This hypothesis is based off our previous data indicating non-water soluble KATP channel agonists produce analgesia and attenuate morphine tolerance in mice. DISCUSSION/SIGNIFICANCE OF FINDINGS: Pharmaceutical strategies to utilize KATP channels for therapeutics have been hindered due to the low solubility and low ability to cross the neurovascular unit. Newly developed, water-soluble KATP channel openers could be useful pharmaceutical strategy to reduce chronic pain, opioid tolerance, and withdrawal in human populations.ABSTRACT IMPACT: Pharmacological activation of K


Standard of care for patients with glioblastoma (GBM) includes resection with concurrent temozolomide (TMZ) and radiotherapy, with inevitable disease recurrence. Upon recurrence, tumors are often resistant to first-line therapies and/or have infiltrated eloquent or deep brain regions, precluding repeat resection. There is currently no standard of care for recurrent GBM and patients succumb to their disease burden within 12- 15 months of their initial diagnosis of recurrence, exposing an unmet need to find novel therapies to treat recurrent disease. Bromodomain and extraterminal (BET) proteins are chromatin readers that affect transcription of genes. The oral BET inhibitor (BETi) OTX-015 has shown promise in a dose-escalation, phase I study in patients with acute leukemia and other BET inhibitors are currently in phase I studies for the treatment of primary brain tumors. We have recently shown that BET inhibition increases DNA damage and mitotic catastrophe in oncogenic cells by increasing transcription-replication conflicts and downregulating expression of key DNA damage checkpoint proteins, and have also shown its efficacy in decreasing tumor burden and improving survival when combined with TMZ in intracranial mouse models of glioma. We have also demonstrated that BETi's synergize with Olaparib by downregulating expression of the BRCA-driven DNA damage repair pathway and further leverages additive effects when triply combined with other DNA damaging agents such as Lomustine to decrease tumor burden and improve survival in patient-derived mouse models of GBM and medulloblastoma. We therefore hypothesize that the synergistic and additive effects of this triple combination seen in our preclinical studies will achieve therapeutic benefits in patients with recurrent GBM.


Skeletal muscle has recently arisen as a novel regulators of Central Nervous System (CNS) function and aging, secreting bioactive molecules known as myokines with proteostasis and metabolism-modifying functions in targeted tissues. We have recently generated a novel transgenic mouse with enhanced muscle proteostasis via moderate overexpression of Transcription Factor E-B (TFEB), a powerful master regulator of cellular clearance and proteostasis. We have discovered that the resulting enhanced skeletal muscle proteostasis function can significantly ameliorate proteotoxicity in the aging CNS and improve cognition and memory in aging mice. These neuroprotective benefits are markedly reminiscent of those observed in the aging CNS post-exercise, suggesting enhancing muscle proteostasis may be sufficient to replicate the local and systemic effects of exercise. Identification of pathways regulating crosstalk between skeletal muscle and CNS may yield targets with high therapeutic potential for diseases of the aging CNS.


Mature cystic teratoma (MCT) is a common benign ovarian germ cell tumor. It is more predominantly seen in premenopausal women and contains at least two or more well-differentiated germ cell layers. It is termed a dermoid cyst if the ectodermal tissue is the predominant component. The complications of a dermoid cyst include torsion, malignant degeneration, rupture, and infection. The incidence of a ruptured dermoid cyst is around 1%-2% resulting in chemical aseptic peritonitis from spillage of the cyst contents. Usual clinical presentation is with diffuse abdominal or pelvic pain and abdominal distension. Around 93-96% of dermoid cysts demonstrate fat in the cyst cavity however, minimal or no fat poses diagnostic challenges. In this case, we discuss a rare case of spontaneously ruptured lipid-poor and thyroid tissue-rich left ovarian dermoid presenting with chemical peritonitis. Special magnetic resonance (MR) Imaging sequences such as fat saturation imaging, chemical shift imaging, and gradient-echo imaging assist in detecting scant amounts of fat in the cyst cavity or cyst wall. Teratomas are the most common ovarian germ cell tumors which arise from primitive germ cells . ConstitA 33-year-old nulligravida presented to the emergency department with acute onset of non-radiating left lower quadrant abdominal pain. The patient reported worsening pain with movement, which gets relieved by lying still. She also reported a progressive increase in abdominal girth over the past several weeks. Denied new vaginal bleeding, discharge, or usage of contraception. Diagnostic imaging with ultrasonography (US), computerized tomography (CT), and magnetic resonance imaging (MRI) were performed in the emergency room and are described in Figures Discovering findings of a ruptured adnexal mass on imaging, the patient underwent exploratory laparotomy with left salpingo-oophorectomy. Intraoperative findings revealed a ruptured left ovarian cyst on the inferior aspect emanating serous fluid into the peritoneal cavity. The tumor was identified as mature lipid-poor cystic teratoma on the frozen section. The postoperative recovery was uneventful. The histopathology of the resected specimen is shown in Figures Ovarian germ cell tumors (OGCTs) are a group of tumors that include benign (mature cystic teratoma [MCT]) or malignant  neoplasms . TeratomUltrasonography (US) is the first line of imaging used in the evaluation of adnexal masses . DiffereIn combination with findings from US, the CT assists in additional fat detection with a sensitivity of 93%-98% . The HouT1-weighted and T2-weighted MRI in MCTs will show a hyper-intense signal representing sebaceous fluid. It can be differentiated from hemorrhagic cyst by fat suppression, chemical shift artifact, or gradient-echo imaging. The fat becomes hypointense on fat-saturated MR Figure , 6, wherThis case study emphasizes the importance of a multimodality approach to complex pelvic masses that present with pelvic pain. Advancement imaging modalities like Pelvic MRI can detect acute complications from these masses like torsion or rupture. Hence, aiding in more accurate diagnosis and pre-operative planning. Surgery is performed for definitive diagnosis and treatment. In the current case of the ruptured teratoma leading to peritonitis, the patient underwent exploratory laparotomy and salpingo-oophorectomy with peritoneal lavage. The ascitic fluid was serous without significant fat content. Histologically, the tissue demonstrated abundant colloidal material and minimal fat consistent with Struma ovarii. The tumor is termed struma ovarii when the thyroid tissue is predominant and comprises >50% of the tumor .In the emergency room setting initial work up for pelvic pain in female patients starts with a good quality ultrasound examination. Upon discovery of a complex mass further evaluation should be done with a pelvic MRI with IV contrast. Pelvic MRI can help identify immediate complications and determine the correct surgical approach. Identifying components of MCTs across multiple imaging modalities assist in differentiating adnexal masses. The wide range of presence of fat in the dermoid cyst makes it easily detectable on CT and MR imaging. Although some cases demonstrate low fat, using special techniques such as fat suppression MRI plays a vital role in early detection and emergency management. Once rupture and peritonitis are suspected, patients should be managed by emergent laparotomy (lower spillage rate than laparoscopy) followed by cystectomy.


Metastasis is an inefficient process in which the vast majority of cancer cells are fated to die, partly because they experience oxidative stress. Metastasizing cancer cells migrate through diverse environments that differ dramatically from their tumor of origin, leading to redox imbalances. The rare metastasizing cells that survive undergo reversible metabolic changes that confer oxidative stress resistance. We review the changes in redox regulation that cancer cells undergo during metastasis. By better understanding these mechanisms, it may be possible to develop pro-oxidant therapies that block disease progression by exacerbating oxidative stress in cancer cells.Oxidative stress often limits cancer cell survival during metastasis, raising the possibility of inhibiting cancer progression with pro-oxidant therapies. This is the opposite strategy of treating patients with antioxidants, an approach that worsened outcomes in large clinical trials. Metastasis is the leading cause of death in patients with cancer because disseminated disease is no longer curable by surgery and is often therapy-resistant . MetastaCancer cells must be plastic to survive metastasis . GeneticMultiple factors contribute to the death of cancer cells during metastasis, including immune-mediated destruction , growth + are important sources of reducing equivalents for oxidative stress resistance  is generally considered an antioxidant, but it exists in oxidized and reduced forms and when it is infused intravenously it selectively kills cancer cells by acting as a pro-oxidant . This isDietary interventions could also have pro-oxidant effects. Ketogenic diets may suppress metastasis partly by increasing oxidative stress in cancer cells . KetogenNew technical approaches to study metastasis, including whole-body imaging of metastasis patterns , improveIn at least some cancers, metastasizing cells appear to experience unusually high levels of oxidative stress, raising the possibility that these cells might be particularly sensitive to pro-oxidant therapies. It is an open question whether such therapies could prevent disease progression in patients with high-risk primary or regionally metastatic lesions. Nonetheless, this merits deeper study in preclinical models. Beyond this big-picture question, there are a number of pressing biological questions central to understanding redox regulation during metastasis: Does oxidative stress limit the survival of metastasizing cells from all cancers or only certain cancers?What causes the oxidative stress experienced by metastasizing cells?Are anabolic pathways downregulated in metastasizing cells to preserve reducing equivalents? Does this sometimes lead to dormancy in metastatic cells?How is mitochondrial function modulated in metastasizing cancer cells as compared with the primary tumors from which they arise?Do micrometastases continue to experience oxidative stress? For how long?To what extent do interactions with immune and stromal cells influence oxidative stress in cancer cells?Do differences in oxidative stress among distinct metastatic sites influence organotropism?


Candidalusitaniae, a previously unreported cause of candidal vaginitis .Increasing use of short-course antifungal therapies in patients with recurrent vulvovaginitis may enable theemergence of less-common, more resistant yeast strains as vaginal pathogens. We report the case of a patient withchronically symptomatic and repeatedly treated vaginal candidiasis whose infection was attributable to


The G-protein-coupled receptors (GPCRs) constitute one of the largest and most ancient superfamilies of membrane proteins. They play a central role in physiological processes affecting almost all aspects of the life cycle of an organism. Availability of the complete sets of putative members of a family from diverse species provides the basis for cross genome comparative studies.Tetraodon complement with the availability of complete sequence of the freshwater puffer fish Tetraodon nigroviridis. Almost all 466 Tetraodon GPCRs (Tnig-GPCRs) identified had a clear human homologue. 189 putative human and Tetraodon GPCR orthologous pairs could be identified. Tetraodon GPCRs are classified into five GRAFS families, by phylogenetic analysis, concurrent with human GPCR classification.We have defined the repertoire of GPCR superfamily of Tetraodon and human genomes displays a high level of orthology and supports large-scale gene duplications in Tetraodon. Examples of lineage specific gene expansions were also observed in opsin and odorant receptors. The human and Tetraodon GPCR sequences are analogous in terms of GPCR subfamilies but display disproportionate numbers of receptors at the subfamily level. The teleost genome with its expanded set of GPCRs provides additional and interesting comparators to study both evolution and function of these receptors.Direct comparison of GPCRs in  The G-protein-coupled receptors (GPCRs) constitute one of the largest and most ancient superfamilies of membrane proteins, accounting for 1–2% of the vertebrate genome. GPCRs are characterized by the presence of highly conserved molecular architecture encoding seven transmembrane (TM) hydrophobic regions linked by three extracellular loops that alternate with three intracellular loops [GPCRs have been aggressively pursued as drug targets due to their central role in physiological processes affecting almost all aspects of the life cycle of an organism . Almost Drosophila; additional species provide new comparators for GPCR studies. Teleost fish, Tetraodon nigroviridis is one of the smallest known vertebrate genomes. It has all the specialized functions of higher vertebrates and can be a good vertebrate model system to study [T. nigroviridis genome now allows for the identification and analysis of its full set of GPCRs. Here, we describe the genome wide survey of Tnig-GPCR repertoire and a detailed analysis of opsin, fish-odorant receptors (FOR) and taste receptors (T1R).The completion of several other vertebrate and invertebrate genome sequencing projects paves the way for "functional genomics". The quest for assigning function to putative gene products exploits the sequence and structural similarities to known genes and further could be elucidated using molecular biology techniques ,10. Suchto study ,15. The Tetraodon nigroviridis genome (>90% sequence coverage) has shown that it possesses one of the smallest known vertebrate genomes and revealed a set of 27,918 predicted genes, much similar to the number of predicted genes in human genome [Tetraodon genome, we developed a comprehensive strategy . For almost all Tnig-GPCRs, a putative human GPCR homologue could be identified. 189 putative human and Tetraodon GPCR orthologous pairs are identified , whereas about two fold as many GPCR sequences as in fugu and about three fourth of the zebrafish GPCRs [Tetraodon also has similar numbers of frizzled receptors as expected in mammals and fish genomes. Some of the gene families in Tetraodon like opsins and fish odorant receptors have shown species-specific expansions similar to trace amine receptors in zebrafish [Tetraodon like other known fish genomes [Rhodopsin family in sh GPCRs . Tetraodebrafish . However genomes .Tetraodon and humans show many GPCRs for which there are two copies in Tetraodon but one in the human genome. Chromosomal distribution of putative Tetraodon-human GPCR orthologous pairs and corresponding Tnig-GPCR paralogs show correspondence between two different chromosomal regions in Tetraodon genome to one region in the human genome , rhodopsin (R), adhesion (A), frizzled (F) and secretin (S) (GRAFS classification) ,23,24.Te 368 see ; A, 29; ebrafish ,25.Tetraodon. These OR genes are found in clusters of 3–4 members in the Tetraodon genome, located on different chromosomes. They display higher sequence identity within a cluster suggesting tandem duplication events might be responsible for OR gene family expansion in Tetraodon as observed in the genomes of every vertebrate organism investigated earlier, including zebrafish, mice and humans [Tetraodon ORs with fish odorant receptor subfamily members  grouped them into six clusters of orthologues with very high boot strap support  were identified in fish odorant receptor (FOR) subfamily of rhodopsins in d humans . Phyloget Figure . In teleh Figure . High diTetraodon genome  taste receptors in e Figure . They haTetraodon GPCRs and found high level of orthology with human counterparts. The human and Tetraodon GPCR sequences are analogous in terms of GPCR subfamilies, but display disproportionate number of receptors at the subfamily level. The teleost genome, with its expanded set of GPCRs, provides an additional and interesting model to study both evolution and function of these receptors. The availability of repertoire of Tetraodon GPCRs will facilitate further studies through "functional genomics" and "reverse pharmacological" strategies to match their cognate ligands and to elucidate biological functions. Systematic mutation of Tetraodon GPCRs will help to determine their neural, developmental and behavioral roles. They might also yield novel insights into the physiological functions and mutational pathologies of their human homologues in particular and other vertebrate homologues in general.We have identified and analyzed repertoire of Tetraodon nigroviridis are obtained from NCBI and Genoscope Tetraodon Genome Browser [12 [Tetraodon nigroviridis EST hits, as there were few or no Tetraodon nigroviridis EST sequences available in the database.Sequences of the  Browser . HumanGP Browser   Sequence alignment of the T1Rs of Tetraodon, human and rat are aligned with the rat mGluR1 metabotropic glutamate receptor (Accession no. P23385). Ligand binding residues of mGluR1 are highlighted in red. The C-terminus is not shown. Potential transmembrane segments are indicated using arrows.Click here for fileTransmembrane Helix (TMH) prediction of human GPCRs by different TMH prediction programs  A dataset of 327 annotated human GPCRs are predicted for Transmembrane Helices (TMH) by HMMTOP, SOSUI, TMHMM and MEMSAT. A range of 6–8 predicted TM helices acquired maximum coverage to predict 7TM domain region.Click here for file


Bacsi A, Choudhury BK, Dharajiya N, Sur S, Boldogh I. 2006. Subpollen particles: carriers of allergenic proteins and oxidases. J Allergy Clin Immunol 118:844–850.During the flowering season, high humidity and moisture trigger the release of pollen grains from grasses, trees, and shrubs. Allergens contained in these pollen grains can cause reactions in the skin, eyes, and upper and lower respiratory tracts. Seasonal asthma also is associated with pollen exposure.How pollen allergens contribute to inflammation in the lower airways has puzzled researchers since few pollen grains reach the peripheral airways due to their size. In this report, NIEHS grantees Sanjiv Sur and Istvan Boldogh, with colleagues at the University of Texas Medical Branch in Galveston, present new findings suggesting that fragments of pollen grains, called sub-pollen particles (SPPs), are capable of reaching the lower airway regions and causing the clinical symptoms associated with seasonal asthma.Ambrosia artemisiifolia) and redroot pigweed (Amaranthus retroflexus) pollen grains. They also used an experimental mouse model of asthma to challenge sensitized mice with intranasally applied SPPs.This same research team recently reported that ragweed pollen grains contain intrinsic NAD(P)H oxidases, and that exposure to them generates oxidative stress in the airway epithelium within minutes of exposure. In the current study, the investigators analyzed bronchial epithelial cells after exposure to hydrated short ragweed H oxidase activity. Exposure of cultured cells to SPPs caused significant increases in the generation of reactive oxygen species and induced airway inflammation in laboratory mice. Pretreatment of the SPPs with NADH and NAD(P)H oxidase inhibitors reduced their ability to increase reactive oxygen species in the airway epithelial cells and reduced airway inflammation.This is the first report to demonstrate the presence of allergenic proteins and oxidase activity in SPPs of respirable size. The study provides insight into the potential role of SPPs in seasonal asthma and suggests that oxidase inhibitors may be useful therapeutic agents in reducing or preventing oxidative damage and inflammation.


We examined the expression of pancreatic secretory trypsin inhibitor (PSTI) in colorectal cancer by immunohistochemical staining using an anti-PSTI antiserum, an in situ hybridisation technique utilising sulphonated PSTI cDNA probe, and a Northern blot hybridisation method, using a 32P-labelled PSTI cDNA probe. Immunohistochemically, PSTI was detected in 80 of 95 (84%) colorectal cancer cases. Analyses with in situ hybridisation as well as Northern blot hybridisation demonstrated PSTI mRNAs in immunohistochemically positive cases, showing PSTI could be produced in colorectal cancerous cells. Histologically well or moderately differentiated adenocarcinoma showed higher incidence of PSTI immunoreactivity than the other types. Furthermore, the intensity of the immunohistochemical staining for PSTI increased the more cases advanced, particularly in regard to depth of invasion and tumour size. Thus, PSTI expression is widespread in colorectal cancer, and occurs more commonly in advanced cases. Considering the suggestion that PSTI is a growth-stimulating factor as an well as inhibitor to proteolytic proteinase, the present findings may indicate that PSTI expressed in colorectal cancerous cells may play a role possibly closely associated with tumour development.