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OBJECTIVE: The objective of this review is to map the international evidence on the implementation of the Buurtzorg model of community nursing practice for the care of older adults. We will describe where and how it has been used, and the challenges and facilitators of implementing this model of care. INTRODUCTION: The challenges of aging have mobilized health systems around the world to replace the current facility- and disease-centered care model with integrated patient-centered care models. The Buurtzorg model provides autonomy to nurses, who, in turn, empower patients in need-based and self-reliant care. INCLUSION CRITERIA: We will consider both published and unpublished studies and reports exploring the process of implementing the Buurtzorg community nursing model for the care of older adults (65 years and older) internationally, in all settings. Concepts of interest will include where the model has been used, how the model has been implemented, and what challenges and facilitators were reported. METHODS: We will implement a three-step search strategy to locate both published and unpublished primary studies, theses, dissertations, book chapters, and text and opinion reports using the following databases: MEDLINE, LILACS, Cochrane CENTRAL, CINAHL, Web of Science, Google Scholar, Embase, Scopus, ProQuest Dissertations and Theses Global, and the official Buurtzorg website. We will present the search strategy in a PRISMA flow diagram. Data will be extracted using Excel spreadsheets and then analyzed narratively. Extracted data will be quantitatively pooled in tables using descriptive statistics to synthesize the characteristics of the reports and sample, followed by a qualitative summary of how the Buurtzorg model has been used, and the challenges and facilitators of implementing this care model.

On the 50th anniversary of Tulving's introduction of the celebrated distinction between episodic and semantic memory, it seems more than fitting to revisit his proposal in light of recent conceptual and methodological advances in the field. This Special Issue of MemoryCognition brings together researchers doing cutting-edge work at the intersection between episodic and semantic memory to showcase studies directly probing this psychological distinction, as well as articles that seek to provide conceptual and theoretical accounts to understand their interaction. The 14 articles presented here highlight the need to critically examine the way in which we conceptualize not only the relationship between episodic and semantic memory, but also the interplay between declarative and non-declarative memory, and the myriad implications of such conceptual changes. In many ways, we suggest this Special Issue might serve as a call to action for our field, inspiring future work to challenge pre-existing conceptions and stimulate new directions in this fast-moving field.

Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients with myocardial dysfunction and delayed ventricular activation, but approximately 25% to 40% of patients do not respond to CRT. Left ventricular (LV) multisite pacing (MSP) has been proposed as a tool to improve CRT response. The goal of this study is to examine the safety and efficacy of LV MSP in CRT nonresponders. Between January 2018, and September 2019, the Strategic Management to Improve CRT Using Multi-Site Pacing trial prospectively enrolled 584 CRT-defibrillator recipients for established indications at 52 sites across the United States and evaluated their response at 6 months using the clinical composite score (CCS). Of the nonresponders, 102 patients had the LV MSP feature turned on and 78 patients completed the 12-month CCS evaluation. The LV MSP feature-related complication-free rate was 99.0% with a lower 95% confidence interval limit of 94.9%, which was higher than the performance goal of 90%. The proportion of nonresponders with an improved CCS from 6 to 12 months was 51.3% with a lower 95% confidence interval limit of 41.4%, which was higher than the performance goal of 5%. The estimated mean reduction in battery longevity with the LV MSP feature was about 3.6 months (estimated battery longevity of 8.87 ± 2.08 years at 6 months and 8.07 ± 2.23 years at 12 months). In conclusion, in CRT nonresponders, the use of the LV MSP feature is safe and associated with a ∼50% conversion rate with a small projected reduction in CRT-defibrillator battery longevity. LV MSP should be considered in the management of CRT nonresponders.

Introduction: Human trafficking is an enormous global threat. Primary care clinicians are part of a safety net of professionals who may be able to identify and assist trafficking in persons (TIPs). The purpose of this systematic review was to explore clinicians’ knowledge, attitudes, and behaviors in identifying and assisting TIPS in health care settings. Methodology: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guided this review. Searches were conducted using PubMed, Medline Plus, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases that yielded 130 articles, of which 10 quantitative articles met eligibility criteria. Eligibility determination, data extraction, synthesis, and evaluation were independently conducted by the authors. Results: Findings revealed deficits in clinician’s knowledge, attitudes, and behaviors on identifying TIPs in clinical settings. In addition, cultural influences affect TIP’s decision-making. Discussion: To support the wide-ranging needs of TIPs, education programs that include clinician trainings on the skills required to identify and assist TIPs across cultures is warranted.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

With pursuit of incremental progress and generalizability of findings in mind, we examined a possible boundary for older and younger adults’ metacognitive distinction between what is not stored in memory versus merely inaccessible with materials that are not process pure to knowledge or events: information regarding news events. Participants were asked questions about public events such as celebrity news, tragedies, and political events that were widely experienced in the previous 10–12 years, responding “I don’t know” (DK) or “I don’t remember” (DR) when retrieval failed. Memories of these events are relatively recently acquired in rich, naturalistic contexts and are likely not fully separated from episodic details. When retrieval failed, DR items were recognized with higher accuracy than DK items, both immediately and 2 years later, confirming that self-reported not remembering reflects failures of accessibility, whereas not knowing better captures a lack of availability. In fact, older adults distinguished between the causes of retrieval failures more precisely than younger adults. Together, these findings advance the reliability, validity, and generalizability of using DR and DK as a metacognitive tool to address the phenomenological experience and behavioral consequences of retrieval failures of information that contains both semantic and episodic features. Implications for metacognition in aging and related constructs like familiarity, remembering, and knowing are discussed.

Stimuli-responsive, on-demand release of drugs from drug-eluting depots could transform the treatment of many local diseases, providing intricate control over local dosing. However, conventional on-demand drug release approaches rely on locally implanted drug depots, which become spent over time and cannot be refilled or reused without invasive procedures. New strategies to noninvasively refill drug-eluting depots followed by on-demand release could transform clinical therapy. Here we report an on-demand drug delivery paradigm that combines bioorthogonal click chemistry to locally enrich protodrugs at a prelabeled site and light-triggered drug release at the target tissue. This approach begins with introduction of the targetable depot through local injection of chemically reactive azide groups that anchor to the extracellular matrix. The anchored azide groups then capture blood-circulating protodrugs through bioorthogonal click chemistry. After local capture and retention, active drugs can be released through external light irradiation. In this report, a photoresponsive protodrug was constructed consisting of the chemotherapeutic doxorubicin (Dox), conjugated to dibenzocyclooctyne (DBCO) through a photocleavable ortho-nitrobenzyl linker. The protodrug exhibited excellent on-demand light-triggered Dox release properties and light-mediated in vitro cytotoxicity in U87 glioblastoma cell lines. Furthermore, in a live animal setting, azide depots formed in mice through intradermal injection of activated azide-NHS esters. After i.v. administration, the protodrug was captured by the azide depots with intricate local specificity, which could be increased with multiple refills. Finally, doxorubicin could be released from the depot upon light irradiation. Multiple rounds of depot refilling and light-mediated release of active drug were accomplished, indicating that this system has the potential for multiple rounds of treatment. Taken together, these in vitro and in vivo proof of concept studies establish a novel method for in vivo targeting and on-demand delivery of cytotoxic drugs at target tissues.

Global warming and the rising prevalence of obesity are well described challenges of current mankind. Most recently, the COVID-19 pandemic arose as a new challenge. We here attempt to delineate their relationship with each other from our perspective. Global greenhouse gas emissions from the burning of fossil fuels have exponentially increased since 1950. The main contributors to such greenhouse gas emissions are manufacturing and construction, transport, residential, commercial, agriculture, and land use change and forestry, combined with an increasing global population growth from 1 billion in 1800 to 7.8 billion in 2020 along with rising obesity rates since the 1980s. The current Covid-19 pandemic has caused some decline in greenhouse gas emissions by limiting mobility globally via repetitive lockdowns. Following multiple lockdowns, there was further increase in obesity in wealthier populations, malnutrition from hunger in poor populations and death from severe infection with Covid-19 and its virus variants. There is a bidirectional relationship between adiposity and global warming. With rising atmospheric air temperatures, people typically will have less adaptive thermogenesis and become less physically active, while they are producing a higher carbon footprint. To reduce obesity rates, one should be willing to learn more about the environmental impact, how to minimize consumption of energy generating carbon dioxide and other greenhouse gas emissions, and to reduce food waste. Diets lower in meat such as a Mediterranean diet, have been estimated to reduce greenhouse gas emissions by 72%, land use by 58%, and energy consumption by 52%.

Acute heart failure is a syndrome defined as the new onset de novo heart failure or worsening [acutely decompensated heart failure (ADHF)] leading to symptoms and signs of HF, mostly related to systemic congestion as based on the European Society of Cardiology (ESC) definition. India has a huge burden of heart failure patients. Several factors have been identified as precipitating acute HF hospitalizations. These include myocardial ischemia, no adherence to medications, arrhythmias, infection, uncontrolled hypertension (HTN), anemia, renal impairment, and diet. However, there is a dearth of studies assessing their effect on mortality in patients admitted with acute heart failure. Many previous studies have shown that BNP and NT-pro-BNP are independent predictors of mortality and other cardiac outcomes in patients with heart failure (HF) and ADHF. However, no studies have provided any clear direction with respect to the critical cut-off values that suggest high mortality. Comprehensive knowledge of the correlation of Pro-BNP and precipitating factors of heart failure with mortality can help in prognostication and clinical management of AHF patients.This was a prospective observational cross-sectional study conducted in the Emergency Department of the Postgraduate Institute of Medical Education and Research, Chandigarh which is a teaching and research hospital located in North India. Patients were enrolled from 1st August 2021 to 28th February 2022. Patients who met inclusion criteria were enrolled; they were followed for 5 days. After 5 days outcomes were recorded. Various precipitating factors for hospitalization were identified and their clinical impact on mortality was noted. Pro-BNP values were obtained at admission and their correlation with mortality and patient outcome after 5 days was noted. Values of Pro-BNP were compared among those who survived after 5 days vs. those who had fatal outcomes.The most common precipitating factor for AHF was poor medical compliance which did not affect mortality. It was followed by sepsis which significantly increases mortality in patients of AHF. ACS was also an important precipitating factor for AHF, though it had no effect on mortality. The mortality in the group of patients with very high Pro-BNP levels ≥ 2000 pg/ml was significantly higher than in the group of patients who had moderately elevated Pro-BNP2000 pg/ml. The median value of Pro-BNP was significantly higher in patients who had fatal outcomes [3670 (IQR- 2745 to 3980)] as compared to patients who survived after 5 days of hospitalization [1340 (IQR- 987 to 1670)].Poor compliance with medications and sepsis are the most common precipitating factors for acute heart failure in north Indian patients. Sepsis as a precipitating factor is a significant risk factor for in-hospital mortality in acute heart failure patients presenting to the emergency department. Pro-BNP values above 2000 pg/ml in patients with acute heart failure requiring emergency admission are associated with a poor prognosis.

Hemoglobinopathies are the most common monogenic disorders in the world with an ever increasing global disease burden each year. As most hemoglobinopathies show recessive inheritance carriers are usually clinically silent. Programmes for preconception and antenatal carrier screening, with the option of prenatal diagnosis are considered beneficial in many endemic countries. With the development of genetic tools such as Array analysis and Next Generation Sequencing in addition to state of the art screening at the hematologic, biochemic and genetic level, have contributed to the discovery of an increasing number of rare rearrangements and novel factors influencing the disease severity over the recent years. This review summarizes the basic requirements for adequate carrier screening analysis, the importance of genotype-phenotype correlation and how this may lead to the unrevealing exceptional interactions causing a clinically more severe phenotype in otherwise asymptomatic carriers. A special group of patients are beta-thalassemia carriers presenting with features of beta-thalassemia intermedia of various clinical severity. The disease mechanisms may involve duplicated alpha-globin genes, mosaic partial Uniparental Isodisomy of chromosome 11p15.4 where the HBB gene is located or haplo-insufficiency of a non-linked gene SUPT5H on chromosome 19q, first described in two Dutch families with beta-thalassemia trait without variants in the HBB gene.

Objectives This study aims to assess the impact of raising the price of sugar and/or sugar-sweetened beverages (SSBs) on caries incidence in the Indian population. Methods A tooth-level decision-analytic model was developed to evaluate a change in caries increment after increasing the price of Sugar and SSBs. The transition of a tooth from a caries-free state to the state of tooth loss in both scenarios was modelled with the help of a Markov model for a time horizon of 63 years, ranging from 2021 to 2083 for the 12-year-old population cohort of India. A conceptual framework was designed to implicate the possible effects of an increase in sugar prices on the reduction of caries incidence. Health effects were estimated in terms of the number of carious lesions and tooth-loss in both the scenarios and modelled as a product of the dose-response relationship between sugar intake and caries incidence. The model was thus used to establish the number of caries lesions prevented, and tooth-loss avoided. Uncertainties in the parameters were assessed using probabilistic sensitivity analysis. The Monte Carlo method was used for simulating the results 1000 times. Results A 20% rise in the price of sugar is expected to result in the prevention of an average of 1.32 teeth in a lifetime of an individual and prevent 27.96 million tooth-loss incidents among the population cohort of India that will eventually lead to a saving of INR (₹) 3116.32 billion (US$ 42.69 billion) on account of dental caries treatment. Similarly, increasing-price of SSBs by 20% will lead to a 0.86% reduction in carious teeth incidence in an individual's lifetime. Conclusion Increasing the cost of sugar and/or SSBs will reduce the daily intake of sugar, which will reduce caries incidence and subsequent progression, thereby preventing caries-attributed tooth-loss and saving treatment costs.

SIGNIFICANCE This analysis and review demonstrate that, although emerging data indicate that the prevalence of severe acute respiratory coronavirus 2 (SARS-CoV-2) on the ocular surface and coronavirus disease 2019 (COVID-19) conjunctivitis is rare, the ocular surface remains of interest as a potential inoculation and transmission site for SARS-CoV-2. Continued safety precautions should be taken as more data become available. COVID-19, caused by SARS-CoV-2, is a novel, global pandemic that has infected millions and, up to this point, caused more than two million fatalities worldwide. The ocular surface has become of interest as a possible vector for transmission by acting as a direct inoculation site, being a conduit for the virus into the respiratory system or as a method of transmission from potentially infected conjunctiva or tears. The components necessary for SARS-CoV-2 to theoretically infect ocular tissues are present: binding receptors (angiotensin-converting enzyme 2 and cluster of differentiation 147) and mechanisms for cell entry (transmembrane protease serine 2 and cathepsin L). This meta-analysis of COVID-19 prevalence data indicates that SARS-CoV-2 RNA has been infrequently found in conjunctival samples when tested with reverse transcriptase–polymerase chain reaction. This review estimates the prevalence of SARS-CoV-2 on the ocular surface and prevalence of conjunctivitis in patients with laboratory-confirmed COVID-19. There is much to be learned regarding ocular tropism of SARS-CoV-2.

This study compared the effects of oral hygiene with a toothpaste formulated with zinc (test) to a fluoride dentifrice (control) for effects on oral polymorphonuclear leukocyte (PMN) as a measure of whole mouth inflammation along with effects on clinical parameters of dental plaque and gingivitis. Adults (age range 18–60 years, n = 212) completed this double-blind, parallel design study. After washout, a baseline oral rinse sample was evaluated for PMN prior to clinical assessments for gingivitis and dental plaque. Subjects were randomly assigned to brush twice daily with either the test or the control toothpaste. Post-treatment evaluations repeated all baseline assessments after 4-week, 6-week and 12-week use of dentifrice with all assessments conducted 12 hours after brushing. PMN reductions in the test were 16.8%, 18.7% and 42.5% at the 4-week, 6-week and 12-week evaluations respectively and significantly different from the control (p < 0.05). The test toothpaste also demonstrated progressively increasing reductions in gingivitis and dental plaque that ranged from 7.6 to 33.3% and 2.3 to 9.1% respectively versus the control (p < 0.05). The test dentifrice demonstrated progressive reductions in oral PMN representing whole mouth inflammation in conjunction with improvements in oral hygiene as compared to the control toothpaste. A hallmark of oral inflammation includes the accumulations of PMN in the afflicted gingival regions to reduce the influences of proliferating microorganisms. Brushing with a zinc dentifrice demonstrated progressive reductions in oral PMN and improvements in oral hygiene as evidenced by progressively lower dental plaque and gingival indices.

BACKGROUND: The effectiveness of music-based interventions (MI) in autism has been attested for decades. Yet, there has been little empirical investigation of the active ingredients, or processes involved in music-based interventions that differentiate them from other approaches. OBJECTIVES: Here, we examined whether two processes, joint engagement and movement, which have previously been studied in isolation, contribute as important active ingredients for the efficacy of music-based interventions. METHODS: In two separate analyses, we investigated whether (1) joint engagement with the therapist, measured using a coding scheme verified for reliability, and (2) movement elicited by music-making, measured using a computer-vision technique for quantifying motion, may drive the benefits previously observed in response to MI (but not a controlled non-MI) in children with autism. RESULTS: Compared to a non-music control intervention, children and the therapist in MI spent more time in triadic engagement (between child, therapist, and activity) and produced greater movement, with amplitude of motion closely linked to the type of musical instrument. CONCLUSIONS: Taken together, these findings provide initial evidence of the active ingredients of music-based interventions in autism.

Case Presentation A 14-year old girl presented with history of productive cough since the age of 3 years. For the past 6 years, she complained of chest tightness and wheezing. There was also nasal stuffiness and discharge for the past 6 years. She denied history of hemoptysis, ear discharge, or chest pain. There was no history of respiratory distress at the time of birth. Her brother also suffered from productive cough and wheezing since the age of 3 years. However, both her parents were asymptomatic.

SARS-CoV-2 can be shed in feces and can enter sewage systems. In order to implement effective control measures and identify new channels of transmission, it is essential to identify the presence of infectious virus particles in feces and sewage. In this study, we attempt to utilize Molecular techniques, cell cultures and animal models to find out the infectivity of SARS-CoV-2 in the feces of COVID-19 patients. Our findings exclude the presence of infectious virus particles, suggesting that fecal-oral transmission may not be the main mode of transmission. Larger-scale initiatives are nevertheless required, particularly considering the emergence of new viral strains.

People can come to “remember” experiences they never had, and these false memories—much like memories for real experiences—can serve a variety of helpful and harmful functions. Sometimes, though, people realize one of their memories is false, and retract their belief in it. These “retracted memories” continue to have many of the same phenomenological characteristics as their believed memories. But can they also continue to serve functions? Across four experiments, we asked subjects to rate the extent to which their retracted memories serve helpful and harmful functions and compared these functions with those served by “genuine” autobiographical memories. People rated their retracted memories as serving both helpful and harmful functions, much like their genuine memories. In addition, we found only weak relationships between people’s belief in their memories and the extent to which those memories served perceived functions. These results suggest memories can serve functions even in the absence of belief and highlight the potential for false memories to affect people’s thinking and behavior even after people have retracted them.

Escherichia albertii has recently been recognized as a zoonotic enteropathogen associated with food poisoning. The reservoirs and transmission routes of this bacterium to humans are still unclear. In this study, we performed a survey of E. albertii in fecal specimens of wild and safeguarded animals in Okayama Prefecture and its prefectural borders, Japan to understand its reservoir in the environment. Forty-two E. albertii were isolated from 10 and 31 droppings of 59 crows and 125 starlings, respectively. Fifty-two E. albertii were isolated from 906 mammal droppings, and out of 52 isolates, origin of 33, 6 and 1 isolates were from martens, foxes, and rabbit, respectively, however, origin of 12 isolates remained unknown. Three E. albertii were isolated from two and one feces of 159 dogs and 76 cats, respectively. Pulsed-filed gel electrophoresis analysis grouped 97 E. albertii strains into 66 pulsotypes including 36 and 30 pulsotypes of isolates from mammals and birds, respectively. E. albertii strains isolated in this study were genetically diverse. Although clonal relationship was not observed between mammal and bird isolates, there were intra- and inter-species relationship in mammalian isolates. All E. albertii strains were positive for eae and Eacdt virulence genes. Furthermore, 20 and 7 strains also carried Eccdt-I and stx2f genes, respectively. Taken together, the results indicate that genetically diverse and potentially virulent E. albertii are distributed among various wild and safeguarded animals in Okayama Prefecture, and the animals could also be reservoirs of E. albertii.

Complications leading to early technical failure have been the Achilles' heel of simultaneous pancreas-kidney transplantation (SPKT). The study purpose was to analyze longitudinally our experience with early surgical complications following SPKT with an emphasis on changes in practice that improved outcomes in the most recent era.Single center retrospective review of all SPKTs from 11/1/01 to 8/12/20 with enteric drainage. Early relaparotomy was defined as occurring within 3 months of SPKT. Patients were stratified into two sequential eras: Era 1 (E1): 11/1/01-5/30/13; Era 2 (E2) 6/1/13-8/12/20 based on changes in practice that occurred pursuant to donor age and pancreas cold ischemia time (CIT).255 consecutive SPKTs were analyzed (E1, n = 165; E2, n = 90). E1 patients received organs from older donors (mean E1 27.3 vs. E2 23.1 years) with longer pancreas cold CITs) (mean E1 16.1 vs. E2 13.3 h, both p .05). E1 patients had a higher early relaparotomy rate (E1 43.0% vs. E2 14.4%) and were more likely to require allograft pancreatectomy (E1 9.1% vs. E2 2.2%, both p .05). E2 patients underwent systemic venous drainage more frequently (E1 8% vs. E2 29%) but pancreas venous drainage did not influence either relaparotomy or allograft pancreatectomy rates. The most common indications for early relaparotomy in E1 were allograft thrombosis (11.5%) and peri-pancreatic phlegmon/abscess (8.5%) whereas in E2 were thrombosis, pancreatitis/infection, and bowel obstruction (each 3%).Maximizing donor quality (younger donors) and minimizing pancreas CIT are paramount for reducing early surgical complications following SPKT.

Congenital heart disease (CHD) is one of the most common forms of birth defects worldwide, with a prevalence of 1–2% in newborns. CHD is a multifactorial disease partially caused by genetic defects, including chromosomal abnormalities and single gene mutations. Here, we describe the Sidra Cardiac Registry, which includes 52 families and a total of 178 individuals, and investigate the genetic etiology of CHD in Qatar. We reviewed the results of genetic tests conducted in patients as part of their clinical evaluation, including chromosomal testing. We also performed whole exome sequencing (WES) to identify potential causative variants. Sixteen patients with CHD had chromosomal abnormalities that explained their complex CHD phenotype, including six patients with trisomy 21. Moreover, using exome analysis, we identified potential CHD variants in 24 patients, revealing 65 potential variants in 56 genes. Four variants were classified as pathogenic/likely pathogenic based on the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) classification; these variants were detected in four patients. This study sheds light on several potential genetic variants contributing to the development of CHD. Additional functional studies are needed to better understand the role of the identified variants in the pathogenesis of CHD.

The role of autophagy in lung cancer cells exposed to waterpipe smoke (WPS) is not known. Because of the important role of autophagy in tumor resistance and progression, we investigated its relationship with WP smoking. We first showed that WPS activated autophagy, as reflected by LC3 processing, in lung cancer cell lines. The autophagy response in smokers with lung adenocarcinoma, as compared to non-smokers with lung adenocarcinoma, was investigated further using the TCGA lung adenocarcinoma bulk RNA-seq dataset with the available patient metadata on smoking status. The results, based on a machine learning classification model using Random Forest, indicate that smokers have an increase in autophagy-activating genes. Comparative analysis of lung adenocarcinoma molecular signatures in affected patients with a long-term active exposure to smoke compared to non-smoker patients indicates a higher tumor mutational burden, a higher CD8+ T-cell level and a lower dysfunction level in smokers. While the expression of the checkpoint genes tested—PD-1, PD-L1, PD-L2 and CTLA-4—remains unchanged between smokers and non-smokers, B7-1, B7-2, IDO1 and CD200R1 were found to be higher in non-smokers than smokers. Because multiple factors in the tumor microenvironment dictate the success of immunotherapy, in addition to the expression of immune checkpoint genes, our analysis explains why patients who are smokers with lung adenocarcinoma respond better to immunotherapy, even though there are no relative differences in immune checkpoint genes in the two groups. Therefore, targeting autophagy in lung adenocarcinoma patients, in combination with checkpoint inhibitor-targeted therapies or chemotherapy, should be considered in smoker patients with lung adenocarcinoma.

The importance of the quinoxaline framework is exemplified by its presence in the well-known drugs such as varenicline, brimonidine, quinacillin, etc. In the past few years, preparation of a variety of organic compounds containing the quinoxaline framework has been reported by several research groups. The chloroquinoxalines were successfully used as substrates in many of these synthetic approaches due to their easy availability along with the reactivity especially towards a diverse range of metal and transition metal-catalyzed transformations including Sonogashira, Suzuki, Heck type of cross-coupling reactions. The transition metals e.g., Pd, Cu, Fe and Nb catalysts played a key role in these transformations for the construction of various CX (e.g., CC, CN, CO, CS, CP, CSe, etc) bonds. These approaches can be classified based on the catalyst employed, type of the reaction performed and nature of CX bond formation during the reaction. Several of these resultant quinoxaline derivatives have shown diverse biological activities which include apoptosis inducing activities, SIRT1 inhibition, inhibition of luciferace enzyme, antibacterial and antifungal activities, cytotoxicity towards cancer cells, inhibition of PDE4 (phosphodiesterase 4), potential uses against COVID-19, etc. Notably, a review article covering the literature based on transition metal-catalyzed reactions of chloroquinoxalines at the same time summarizing the relevant biological activities of resultant products is rather uncommon. Therefore, an attempt is made in the current review article to summarize (i) the recent advances noted in the transition metal-catalyzed reactions of chloroquinoxalines (ii) with the relevant mechanistic discussions (iii) along with the in vitro, and in silico biological studies (wherever reported) (iv) including Structure-Activity Relationship (SAR) within the particular series of the products reported between 2010 and 2022.

Adults and children with typical development (TD) remember vocal melodies (without lyrics) better than instrumental melodies, which is attributed to the biological and social significance of human vocalizations. Here we asked whether children with autism spectrum disorder (ASD), who have persistent difficulties with communication and social interaction, and adolescents and adults with Williams syndrome (WS), who are highly sociable, even indiscriminately friendly, exhibit a memory advantage for vocal melodies like that observed in individuals with TD. We tested 26 children with ASD, 26 adolescents and adults with WS of similar mental age, and 26 children with TD on their memory for vocal and instrumental (piano, marimba) melodies. After exposing them to 12 unfamiliar folk melodies with different timbres, we required them to indicate whether each of 24 melodies (half heard previously) was old (heard before) or new (not heard before) during an unexpected recognition test. Although the groups successfully distinguished the old from the new melodies, they differed in overall memory. Nevertheless, they exhibited a comparable advantage for vocal melodies. In short, individuals with ASD and WS show enhanced processing of socially significant auditory signals in the context of music. LAY SUMMARY: Typically developing children and adults remember vocal melodies better than instrumental melodies. In this study, we found that children with Autistic Spectrum Disorder, who have severe social processing deficits, and children and adults with Williams syndrome, who are highly sociable, exhibit comparable memory advantages for vocal melodies. The results have implications for musical interventions with these populations.

Background Herbal smoking products (HSPs) are marketed as a safer alternative to tobacco. These are easily available at affordable prices in the online retail websites. This study aimed to analyze the HSP-related informational content available in the most popular online platforms. Methods Google, Yahoo, Bing and YouTube online platforms were searched for HSP related content using appropriate keywords. First 50 search results were retrieved and screened for potential eligibility. The included web-pages were categorized as video and still records. From each included record, information regarding source, primary theme, health benefits/hazards and tone was abstracted. Additionally, video production quality, like ratio and video power index was also computed for each video record. All included records were subjected to descriptive statistics and Chi-square test, as appropriate. Level of significance was set at Results 174 still and 94 video records were included. 35.6% of the included still records were sourced by manufacturers/suppliers while that of scientific origin was 12.1%. 83% of the video-records were posted by general public. About 90% of the included records had not mentioned anything regarding age restrictions. 67.8% of the still records and 87.2% of the video records promoted the use of HSPs. Conclusions The informational content presented online is huge, mostly posted by the general public without any scientific rationale and exclusively favors the use of HSPs. There is no age restriction as to who can access the information, making this content easily accessible to people of all ages. Such spread of information may mislead the public in adopting the smoking of these herbal products. Since HSPs may act as a potential gateway to tobacco smoking, there is an urgent need to regulate the content available online.

General knowledge questions are used across a variety of research and clinical settings to measure cognitive processes such as metacognition, knowledge acquisition, retrieval processes, and intelligence. Existing norms only report performance in younger adults, rendering them of limited utility for cognitive aging research because of well-documented differences in semantic memory and knowledge as a function of age. Specifically, older adults typically outperform younger adults in tasks assessing retrieval of information from the knowledge base. Here we present older adult performance on 421 general knowledge questions across a range of difficulty levels. Cued recall data, including data on the phenomenology of retrieval failures, and multiple-choice data are available. These norms will allow researchers to identify questions that are not likely to be known by older adult participants to examine learning or acquisition processes, or to select questions within a range of marginal accessibility, for example. Comparisons with young adult data from prior databases confirms previous findings of greater knowledge in older adults and indicates there is preservation of knowledge from early adulthood into older adulthood. Supplementary Information The online version contains supplementary material available at 10.3758/s13428-020-01493-2.

von Willebrand factor (VWF) is an essential hemostatic protein that is synthesized in endothelial cells and stored in Weibel-Palade bodies (WPBs). Understanding the mechanisms underlying WPB biogenesis and exocytosis could enable therapeutic modulation of endogenous VWF, yet optimal targets for modulating VWF release have not been established. Because biogenesis of lysosomal related organelle-2 (BLOC-2) functions in the biogenesis of platelet dense granules and melanosomes, which like WPBs are lysosome-related organelles, we hypothesized that BLOC-2–dependent endolysosomal trafficking is essential for WPB biogenesis and sought to identify BLOC-2–interacting proteins. Depletion of BLOC-2 caused misdirection of cargo-carrying transport tubules from endosomes, resulting in immature WPBs that lack endosomal input. Immunoprecipitation of BLOC-2 identified the exocyst complex as a binding partner. Depletion of the exocyst complex phenocopied BLOC-2 depletion, resulting in immature WPBs. Furthermore, releasates of immature WPBs from either BLOC-2 or exocyst-depleted endothelial cells lacked high-molecular weight (HMW) forms of VWF, demonstrating the importance of BLOC-2/exocyst-mediated endosomal input during VWF maturation. However, BLOC-2 and exocyst showed very different effects on VWF release. Although BLOC-2 depletion impaired exocytosis, exocyst depletion augmented WPB exocytosis, indicating that it acts as a clamp. Exposure of endothelial cells to a small molecule inhibitor of exocyst, Endosidin2, reversibly augmented secretion of mature WPBs containing HMW forms of VWF. These studies show that, although BLOC-2 and exocyst cooperate in WPB formation, only exocyst serves to clamp WPB release. Exocyst function in VWF maturation and release are separable, a feature that can be exploited to enhance VWF release.

To compare the effectiveness of topical fluoride—antibacterial agent combined therapy versus topical fluoride monotherapy in preventing dental caries among 1- to 16-year-old children. PubMed, EbscoHost, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials were searched for randomised controlled trials. The trials should have assessed the caries-preventive effectiveness of topical fluoride-antibacterial agent (Povidone Iodine/Chlorhexidine/Xylitol/Triclosan/Cetylpyridinium Chloride) combined therapy versus topical fluoride monotherapy among children. Out of 3475 records that were screened, full text of 41 articles was assessed for potential inclusion. Sixteen trials that fulfilled the eligibility criteria were subjected to qualitative synthesis. The risk of bias was assessed using the Cochrane Collaboration’s tool. Continuous data from nine trials were pooled using Inverse Variance test in meta-analysis function of Review Manager (version 5.4). GRADE approach was used to analyse the certainty of evidence. Statistical heterogeneity was quantified using the I2 statistic. A p-value of

Metabolic alterations in cancer represent convergent effects of oncogenic mutations. We hypothesized that a metabolism-restricted genetic screen, comparing normal primary mouse hematopoietic cells and their malignant counterparts in an ex vivo system mimicking the bone marrow microenvironment, would define distinctive vulnerabilities in acute myeloid leukemia (AML). Leukemic cells, but not their normal myeloid counterparts, depended on the aldehyde dehydrogenase 3a2 (Aldh3a2) enzyme that oxidizes long-chain aliphatic aldehydes to prevent cellular oxidative damage. Aldehydes are by-products of increased oxidative phosphorylation and nucleotide synthesis in cancer and are generated from lipid peroxides underlying the non–caspase-dependent form of cell death, ferroptosis. Leukemic cell dependence on Aldh3a2 was seen across multiple mouse and human myeloid leukemias. Aldh3a2 inhibition was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects AML cells. Inhibiting Aldh3a2 provides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic state of malignant cells.

Health disparities across ethnic or racial groups are typically examined through single behavior at a time. The syndemics and multimorbidity health disparities have not been well examined by race. In this study, we study health disparities by identifying the networks of multimorbidities among individuals from seven population groups based on race, including White, African American, Asian, Hispanic, Native American, Bi- or Multi-racial and Pacific Islander. We examined a large electronic medical record (EMR) containing health records of more than 18.7 million patients and created multimorbidity networks considering their lifetime history from medical records in order to compare the network properties among seven population groups. In addition, the networks at organ system level depicting the relationship among disorders belonging to different organ systems are also compared. Our macro analysis at the organ-level indicates that African-Americans have a stronger multimorbidity network followed by Whites and Native Americans. The networks of Asians and Hispanics are sparse. Specifically, the relationship of infectious and parasitic disorders with respiratory, circulatory and genitourinary system disorders is stronger among African Americans than others. On the other hand, the relationship of mental disorders with respiratory, musculoskeletal system and connective tissue disorders is more prevalent in Whites. Similar other disparities are discussed. Recognition and explanation of such differences in multimorbidities inform the public health policies, and can inform clinical decisions as well. Our multimorbidity network analysis identifies specific differences in diagnoses among different population groups, and presents questions for biological, behavioral, clinical, social science, and policy research.

To study the temporal trends in cytologic detection of cervical epithelial cell abnormalities (ECA) and to evaluate the impact of introduction of endocervical brush sampling on detection of ECA.This was a cross-sectional study of conventional cervical smears collected over a 13 year period (2006-2018). The study was divided into two time periods (TP)-TP1 (2006-2014, 67,437 smears) using only extended tip Ayre's spatula and TP2 (2015-2018; 36,746 smears) when Cytobrush Papsmear kit (Ayre's spatula + endocervical brush) was used. The unsatisfactory rate and detection rate of ECA was compared between the two TPs.The unsatisfactory rate reduced from 4.7 % in TP 1-1.5% in TP2 (P 0.001). The frequency of ECA was 1.5 % in TP1 and 1.9 % in TP2 (P 0.001). A significantly higher number of ASC-H and HSIL were detected in TP2. There was a substantial improvement (3.7 times) in detection of glandular abnormalities overall (P 0.001), as also for both the qualifiers AGC- NOS (4.4 times) and AGC- FN (3.3 times) in TP2.Cervical sampling using combined spatula and endocervical brush reduces the unsatisfactory rate and improves the detection of both squamous and glandular precancerous lesions. Hence, this sampling procedure should be recommended for all laboratories practicing conventional cervical cytology.

There is a paucity of trained cytopathologists in low-resource settings for effective cervical cancer screening. There has been no documented report of the impact of a dedicated training program in cervical cytology on pathologists’ knowledge and skill in this field. The present study aimed to evaluate the efficacy of the regularly conducted training workshops on the attending pathologists’ knowledge, practice, and skills in cervicovaginal smear reporting. Our institute, a premier cancer research institute, has conducted 10 cytology-based cervical cancer screening workshops for pathologists with pre- and post-training evaluation using sets of digital images and a questionnaire (knowledge score). Additionally, feedback on diagnostic skills was taken at a 1-month and 6-month interval post-workshop using a separate set of digital images of cervical lesions. A Google form-based questionnaire was designed to seek the participants’ feedback on the perceived improvement in knowledge and skills. All the data thus collected were analyzed to assess the efficacy of these workshops in imparting the desired knowledge and skills. A total of 350 participants were enrolled in these workshops. The average knowledge score improved from 10.56 (± 3.23) in the pre-training questionnaire to 21.17 (± 2.41) in the post-training evaluation, making a 100.5% increase (P

Objectives Varicella zoster virus (VZV) infection is reported regularly among adolescents and adults in Caribbean island populations. The disease more often runs a severe course among these populations, causing a substantial burden. The aim of this sero-epidemiological study was to obtain an insight into VZV susceptibility and its determinants in island populations of the Caribbean Netherlands (CN). Methods Participants from Bonaire, St. Eustatius, and Saba (n = 1829, aged 0–90 years) donated a blood sample and completed a questionnaire. VZV-specific IgG antibodies were determined using a bead-based multiplex immunoassay. Risk factors were analysed using a logistic regression model. Results Overall seroprevalence in CN was 78%, being lowest on St. Eustatius (73%) and highest on Bonaire and Saba (79%). Seropositivity increased gradually with age, with 60% and 80% at ages 10 years and 30 years, respectively, and ranging between 80% and 90% thereafter. Higher odds for VZV seronegativity were seen among persons who were born in CN or had resided there since early childhood, and among single-person households. Conclusions VZV susceptibility is relatively high among adolescents and adults in CN. In order to reduce the burden of VZV-related disease in these populations, routine varicella vaccination is recommended. As data are scarce, the study findings can serve as a blueprint for the epidemiology in tropical regions.

How do we know when a remembered event took place? Contemporary theories suggest that temporal landmarks, conventional time patterns, transitions, and lifetime periods, among other strategies, help reconstruct the date of an event. Spatial information plays a privileged role in participants' experiences of reliving and vividness during remembering. Given its influence on these key properties, we conducted two experiments with undergraduate students (n

Sjogren syndrome is an autoimmune disease characterised by lymphocytic infiltration and inflammation of the exocrine glands resulting in decreased secretion of involved glands which manifests mostly as dry eye and dry mouth. The prevalence of the disease is reported to be about 10.3 per 10,000 population. It is more common in females with a male: female ratio of 16:1. Extra glandular manifestations are seen in up to 1/3rd of the cases. Renal involvement is seen in 4.9% of patients with Sjogren syndrome.Here we present three cases of Sjogren Syndrome who presented to our hospital with hypokalaemic quadriparesis.On evaluation all three of the patients were found to have renal tubular acidosis type 1. None of these patients had any symptom of Sjogren syndrome before the onset of quadriparesis. All of these patients had acute onset progressive areflexic quadriparesis with involvement of facial muscles and drooping of eyelids without sensory or bladder bowel involvement. One of these patients had respiratory muscle paralysis severe enough to mandate mechanical ventilation. Arterial Blood Gas analysis and urine electrolyte analysis were suggestive of type 1 renal tubular acidosis. ANA positive in 2 of the 3 patients. Anti-SSAamp; anti-SSB antibodies were positive in all three patients. Supportive measures and IV fluid and electrolyte correction was done. There was complete recovery of power in all three patients and were discharged on oral medications.Renal Tubular Acidosis is characterised by inability of the nephrons to maintain physiologic acid base balance. This usually results from a defect in the tubular transport mechanisms. Distal Renal tubular acidosis (as in these patients) is further defined by an alkalotic urinary pH(gt;5.5) and profound hypokalemia due to impairment in H+ secretion in ditstal tubular alpha-intercalated cells. Owing to this imbalance of ionic transport in distal tubules there can be nephrocalcinosis, nephrolithiasis, rickets and severe muscle weakness. Sjogren syndrome is one of the etiologies leading to development of T1RTA.T1RTA can be the presenting feature of Sjogren Syndrome.Though a rare manifestation of the disease if can be the presenting symptom. Work up for RTA (ABG, urine electrolytes, Urine PH and osmolarity etc) in patients with hypokalaemic paresis can help establish the etiological diagnosis(ANA, anti-SSA,anti-SSB) and help prevent future relapses of the disease.

β-catenin signaling, and angiogenesis are associated with colospheroid (CSC), development. CSCs, spheroids derived from colon cancer cells, are responsible for metastasis, drug resistance, and disease recurrence. Whether dysregulating β-catenin and inhibiting angiogenesis reduce CSC growth is unknown. In this study, the molecular mechanism of CSC growth inhibition was evaluated using a novel combination of melatonin (MLT) and andrographolide (AGP). These drugs have anticarcinogenic, antioxidant, and antimetastatic properties. CSCs were obtained from two metastatic colon cancer cell lines (HT29 and HCT-15). The viability and stemness were monitored (FDA propidium iodide staining and immunoblot for CD44, CD133, Nanog, Sox2, and Oct4). The drug combination synergistically diminished stemness via increased reactive oxygen species (ROS) levels, reduced mitochondrial membrane potential and ATP level. MLT + AGP induced cell death by inhibiting β-catenin expression and its downregulatory signals, Cyclin D1, c-Myc. MLT + AGP treated cells exhibited translocation of phospho-β-catenin to the nucleus and dephosphorylated-β-catenin. Downregulation of β-catenin activation and its transcription factors (TCF4 and LEF1) and GTP binding/G-protein related activity were found in the dual therapy. Angiogenic inhibition is consistent with downregulation of VEGF messenger RNA transcripts (VEGF189), phosphorylated VEGF receptor protein expression, matrigel invasion, and capillary tube inhibition. In vivo, the intravenous injection of MLT + AGP slowed HT29 metastatic colon cancer. Histopathology indicated significant reduction in microvascular density and tumor index. Immunohistochemistry for caspase 7, and β-catenin found increased apoptosis and downregulation of β-catenin signals. The mechanism(s) of decreased colospheroids growth were the inhibition of the Wnt/β-catenin pathway. Our results provide a rationale for using MLT in combination with AGP for the inhibition of CRCs.

A user-calibrated real-time continuous glucose monitoring (rt-CGM) system is compared to a factory-calibrated flash glucose monitoring (FGM) system and assessed in terms of accuracy and acceptability in patients with type 1 diabetes (T1D).Ten participants with T1D were enroled from a specialist diabetes centre in Singapore and provided with the Guardian Connect with Enlite Sensor (Medtronic, Northridge, CA, USA) and first-generation Freestyle Libre System (Abbott Diabetes Care, Witney, UK), worn simultaneously. Participants had to check capillary blood glucose four times per day. At the end of week 1 and week 2, participants returned for data download and were given a user evaluation survey.Accuracy evaluation between Guardian Connect and Freestyle Libre includes the overall mean absolute relative difference value (9.7 ± 11.0% vs. 17.5 ± 10.9%), Clarke Error Grid zones A + B (98.6% vs. 98.1%), sensitivity (78.9% vs. 63.4%), and specificity (93.4% vs. 81.0%). Notably, time below range (3.9 mmol/L) was 10.5% for FGM versus 2% for rt-CGM. From the evaluation survey, 90% of participants perceived rt-CGM to be accurate versus 40% for FGM, although the majority found both devices to be easy to use, educational, and useful in improving glycaemic control. However, due to the cost of sensors, only 30% were keen to use either device for continuous monitoring.Although rt-CGM was superior to FGM in terms of accuracy, the value of glucose trends in both devices is still useful in diabetes self-management. Patients and clinicians may consider either technology depending on their requirements.

Machine learning (ML)-workflows enable unprejudiced/robust evaluation of complex datasets. Here, we analyzed over 490,000,000 data points to compare 10 different ML-workflows in a large (N=11,652) training dataset of human pancreatic single-cell (sc-)transcriptomes to identify genes associated with the presence or absence of insulin transcript(s). Prediction accuracy/sensitivity of each ML-workflow was tested in a separate validation dataset (N=2,913). Ensemble ML-workflows, in particular Random Forest ML-algorithm delivered high predictive power (AUC=0.83) and sensitivity (0.98), compared to other algorithms. The transcripts identified through these analyses also demonstrated significant correlation with insulin in bulk RNA-seq data from human islets. The top-10 features, (including IAPP, ADCYAP1, LDHA and SST) common to the three Ensemble ML-workflows were significantly dysregulated in scRNA-seq datasets from Ire-1αβ-/- mice that demonstrate dedifferentiation of pancreatic β-cells in a model of type 1 diabetes (T1D) and in pancreatic single cells from individuals with type 2 Diabetes (T2D). Our findings provide direct comparison of ML-workflows in big data analyses, identify key elements associated with insulin transcription and provide workflows for future analyses.

A clinically comparable Convolutional Neural Network framework-based technique for performing automated classification of cancer grades and tissue structures in hematoxylin and eosin-stained colon histopathological images is proposed in this paper. It comprised of Enhanced Convolutional Learning Modules (ECLMs), multi-level Attention Learning Module (ALM), and Transitional Modules (TMs). The ECLMs perform a dual mechanism to extract multi-level discriminative spatial features and model cross-channel correlations with fewer computations and effectual avoidance of vanishing gradient issues. The ALM performs focus-refinement through the channel-wise elemental attention learning to accentuate the discriminative channels of the features maps specifically belonging to the important pathological regions and the scale-wise attention learning to facilitate recalibration of features maps at diverse scales. The TMs concatenate the output of these two modules, infuse deep multi-scalar features and eliminate resolution degradation issues. Varied pre-processing techniques are further employed to improvise the generalizability of the proposed network. For performance evaluation, four diverse publicly available datasets (Gland Segmentation challenge(GlaS), Lung Colon(LC)-25000, Kather_Colorectal_Cancer_Texture_Images (Kather-5k), and NCT_HE_CRC_100K(NCT-100k)) and a private dataset Hospital Colon(HosC) are used that further aids in building network invariance against digital variability that exists in real-clinical data. Also, multiple pathologists are involved at every stage of the proposed research and their verification and approval are taken for each step outcome. For the cancer grade classification, the proposed model achieves competitive results for GlaS (Accuracy(97.5%), Precision(97.67%), F1-Score(97.67%), and Recall(97.67%)), LC-25000 (Accuracy(100%), Precision(100%), F1-Score(100%), and Recall(100%)), and HosC(Accuracy(99.45%), Precision(100%), F1-Score(99.65%), and Recall(99.31%)), and while for the tissue structure classification, it achieves results for Kather-5k(Accuracy(98.83%), Precision(98.86%), F1-Score(98.85%), and Recall(98.85%)) and NCT-100k(Accuracy(97.7%), Precision(97.69%), F1-Score(97.71%), and Recall(97.73%)). Furthermore, the reported activation mappings of Gradient-Weighted Class Activation Mappings(Grad-CAM), Occlusion Sensitivity, and Local Interpretable Model-Agnostic Explanations (LIME) evidence that the proposed model can itself learn the similar patterns considered pertinent by the pathologists exclusive of any prerequisite for annotations. In addition, these visualization results are inspected by multiple expert pathologists and provided with a validation score as (GlaS(9.251), LC-25000(9.045), Kather-5k(9.248), NCT-100k(9.262), and HosC(9.853)). This model will provide a secondary referential diagnosis for the pathologists to ease their load and aid them in devising an accurate diagnosis and treatment plan.

The influence of African American (AA) recipient race on outcomes following simultaneous pancreas-kidney transplantation (SPKT) is uncertain.From 11/01 to 2/19, we retrospectively studied 158 Caucasian (C) and 57 AA patients (pts) undergoing SPKT.The AA group had fewer patients on peritoneal dialysis (30% C vs. 14% AA), more patients with longer dialysis duration (28% C vs. 51% AA), more sensitized (PRA ≥20%) patients (6% C vs. 21% AA), and more patients with pretransplant C-peptide levels ≥2.0 ng/ml (11% C vs. 35% AA, all P .05). With a mean 9.2 year follow-up, patient survival (65% C vs. 77% AA, P = .098) slightly favored the AA group, whereas kidney (55% C vs. 60% AA) and pancreas (48% C vs. 54% AA) graft survival rates (GSRs) were comparable. Death-censored kidney (71% C vs. 68% AA) and pancreas (both 62%) GSRs demonstrated that death with a functioning graft (DWFG) was more common in C vs. AA patients (23% C vs. 12% AA, P = .10). The incidence of death-censored dual graft loss (usually rejection) was 7% C versus 21% AA (P = .005).Following SPKT, AA patients are at a greater risk for dual immunological graft loss whereas C patients are at greater risk for DWFG.

The purpose of this review is to chronicle the history of dual kidney transplantation (DKT) and identify opportunities to improve utilization of marginal deceased donor (MDD) kidneys through DKT.The practice of DKT from adult MDDs dates back to the mid-1990s, at which time the primary indication was projected insufficient nephron mass from older donors. Multiple subsequent studies of short- and long-term success have been reported focusing on three major aspects: Identifying appropriate selection criteria/scoring systems based on pre- and postdonation factors; refining technical aspects; and analyzing longer-term outcomes. The number of adult DKTs performed in the United States has declined in the past decade and only about 60 are performed annually. For adult deceased donor kidneys meeting double allocation criteria,60% are ultimately not transplanted. MDDs with limited renal functional capacity represent a large proportion of potential kidneys doomed to either discard or nonrecovery.DKT may reduce organ discard and optimize the use of kidneys from MDDs. New and innovative technologies targeting ex vivo organ assessment, repair, and regeneration may have a major impact on the decision whether or not to use recovered kidneys for single or DKT.