Anticholinergic deprescribing: A case report demonstrating improved cognition and function with minimal adverse withdrawal effects.

Anticholinergic-induced cognitive impairment may be partially reversible upon cessation. A barrier to deprescribing of anticholinergics is the unknown risk of anticholinergic adverse drug withdrawal events (ADWE), with only limited information available on the incidence, timing and severity of anticholinergic ADWE. We report the case of a 76-year-old woman who experienced significant cognitive improvement following deprescribing long-term use of a strong anticholinergic drug, doxepin, and dose reduction of another possible anticholinergic agent. The patient decided to abruptly stop taking doxepin, despite a planned careful taper with twice weekly monitoring, but did not experience any severe anticholinergic ADWE and subsequently had significantly improved cognitive function. Future research should focus on better understanding the risk of anticholinergic ADWE so that anticholinergic deprescribing decisions, including how often and by how much to taper, can be made confidently and safely.

Preliminary Analysis of Fall Concern Among Family Caregivers of Older Adults Discharged From the Hospital: A Psychometric Evaluation of the Carers' Fall Concern Instrument.

PURPOSE: To provide a preliminary descriptive analysis of the change in fall concern among family caregiver-care recipient dyads during hospitalization and after discharge as part of a prospective study exploring the psychometric properties of the Carers' Fall Concern Instrument. METHOD: Using a prospective cohort design, an interviewer-administered survey was completed by dyads at 48 hours before discharge and 1 week and 30 days after discharge. RESULTS: Of family caregivers, 76.9% thought their care recipient was at risk of falling and 61.5% were afraid of them falling. However, only 34.6% of older adults thought that they were at risk of falling and only 42.3% were afraid of falling. Family caregivers reported significantly less concern about falls after their care recipients were discharged. CONCLUSION: This study provided greater insight into caregiver-care recipient dyads' fall concern during their transition from hospital to home that may guide post-discharge fall prevention education on falls. [Journal of Gerontological Nursing, 50(5), 14-18.].

Comorbid depression among adults with heart failure in Ethiopia: a hospital-based cross-sectional study.

BACKGROUND: Depression is a common comorbidity in adults with heart failure. It is associated with poor clinical outcomes, including decreased health-related quality of life and increased morbidity and mortality. There is a lack of data concerning the extent of this issue in Ethiopia. Consequently, this study aimed to assess the prevalence of comorbid depression and associated factors among adults living with heart failure in Ethiopia. METHODS: A hospital-based cross-sectional study was conducted at the cardiac outpatient clinics of two selected specialist public hospitals in Addis Ababa, Ethiopia: St. Paul's Hospital Millennium Medical College and St. Peter Specialized Hospital. An interviewer-administered questionnaire was used to collect data from 383 adults with heart failure who attended the clinics and met the inclusion criteria. Depression was measured using the Patient Health Questionnaire (PHQ-9). A binary logistic regression model was fitted to identify factors associated with depression. All statistical analyses were conducted using STATA version 17 software. RESULTS: The mean age of the participants was 55 years. On average, participants had moderate depression, as indicated by the mean PHQ-9 score of 11.02 ± 6.14, and 217 (56.6%, 95%CI 51.53-61.68) had comorbid depression. Significant associations with depression were observed among participants who were female (AOR: 2.31, 95%CI:1.30-4.08), had comorbid diabetes mellitus (AOR: 3.16, 95%CI: 1.47-6.82), were classified as New York Heart Association (NYHA) class IV (AOR: 3.59, 95%CI: 1.05-12.30), reported poor levels of social support (AOR: 6.04, 95%CI: 2.97-12.32), and took more than five medications per day (AOR: 5.26, 95%CI: 2.72-10.18). CONCLUSIONS: This study indicates that over half of all adults with heart failure in Ethiopia have comorbid depression, influenced by several factors. The findings have significant implications in terms of treatment outcomes and quality of life. More research in the area, including interventional and qualitative studies, and consideration of multifaceted approaches, such as psychosocial interventions, are needed to reduce the burden of comorbid depression in this population.

Occupational exposures among women beedi workers in Mysore District, India: A mixed-methods study protocol.

Beedi is the most common smoking form of tobacco used in India. The rolling of beedis is performed primarily by women in settings that lack occupational safeguards. The aims of this protocol are to establish methods for the study of occupational exposures among women beedi workers and their experiences and challenges working with unburnt tobacco. This protocol employs a convergent parallel mixed-methods approach. Qualitatively, we plan to explore the experiences and challenges faced by women beedi workers using photovoice, a community based participatory method. Occupational exposures to pesticides will be assessed through the use of silicone wristbands worn for seven days by workers, and exposure to toxic metals and metalloids will be assessed in dust samples collected in the homes of workers. The outcomes will be analyzed to form policy recommendations to improve the occupational health of women beedi workers.

Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

Linear and curvilinear association of pain tolerance and social anxiety symptoms among youth with different subgroups of childhood trauma.

BACKGROUND: Social anxiety is a common symptom that occurs after exposure to childhood trauma (CT), and pain tolerance is a protective factor against social anxiety in generic populations with CT. However, few studies have investigated whether and how this association varies across different CT subgroups. Thus, this study aimed to investigate (1) the effects of pain tolerance on social anxiety symptoms among youth with different subgroups of CT; (2) the nonlinear relationship between pain tolerance and social anxiety symptoms among different CT categories. METHODS: In this study, 15,682 college or university students with experiences of CT were identified in a large sample and divided into five CT subgroups. Linear and quadratic regression models were conducted to explore the association between pain tolerance and social anxiety symptoms among youth with different CT subgroups. RESULTS: The results of model revealed a linear relationship between pain tolerance and social anxiety symptoms among youth with most CT subgroups. Notably, an inverted U-shaped curve was found between pain tolerance and social anxiety symptoms in youth with emotional abuse. Social anxiety symptoms increased gradually with pain tolerance scores between 0 and 16, and then sharply decreased when scores reached above 16. LIMITATIONS: Limited by self-report measurements, the results of this study focused only on perceived pain tolerance and ignored behavioral pain tolerance. CONCLUSION: These findings highlight the importance of assessing pain tolerance thresholds in youth with emotional abuse and improving pain tolerance to prevent social anxiety symptoms in youth with different subgroups of CT.

Clinical nurse managers' leadership styles and staff nurses' work engagement in Saudi Arabia: A cross-sectional study.

BACKGROUND: Effective nurse leadership enhances nurse welfare, improves patient care, and increases organisational success. A lack of adequate, supportive leadership significantly contributes to many nurses leaving the profession. Nurse managers need to prioritise engagement and retention as significant focus areas to address the nursing shortage in Saudi Arabia and accomplish the national program's objectives. AIM: To examine the correlation between the leadership styles of clinical nurse managers and staff engagement. METHOD: This study used a descriptive, cross-sectional, correlational design. The leadership styles of clinical nurse managers were evaluated using the Multifactor Leadership Questionnaire (MLQ-5X). Work engagement was assessed using the Utrecht Work Engagement Scale (UWES). Questionnaires were distributed to 450 nurses in four public hospitals in western Saudi Arabia. Non-probability convenience sampling was used to collect the data. RESULTS: A total of 278 nurses from a range of clinical areas participated in the survey, which revealed that the leadership styles of clinical nurse managers positively or negatively impact nurse work engagement. Most clinical nurse managers exhibit transformational leadership, followed by transactional, then passive-avoidant styles. Respondents displayed a high level of work engagement, emphasising the positive impact of transformational and transactional leadership on work engagement outcomes. The findings showed significant differences in leadership styles and work engagement levels between Saudi and non-Saudi nurses across various dimensions. CONCLUSION: Understanding the effect of leadership styles employed by nurse managers on work engagement can positively impact staff retention rates and the quality of patient care. Nurse managers should participate in training programs to enhance their practical leadership skills to enhance the work engagement levels of nurses. IMPLICATION: Nurse work engagement can be improved by establishing training programs that promote effective leadership and highlight the significance of various leadership styles and their subsequent impact on nurse work engagement. Nursing students should receive education on leadership styles. Nursing leaders should be given access to mentoring programs and opportunities for career advancement to support the introduction of effective leadership styles.

ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes.

Cerebral creatine deficiency syndromes (CCDS) are inherited metabolic phenotypes of creatine synthesis and transport. There are two enzyme deficiencies, guanidinoacetate methyltransferase (GAMT), encoded by GAMT and arginine-glycine amidinotransferase (AGAT), encoded by GATM, which are involved in the synthesis of creatine. After synthesis, creatine is taken up by a sodium-dependent membrane bound creatine transporter (CRTR), encoded by SLC6A8, into all organs. Creatine uptake is very important especially in high energy demanding organs such as the brain, and muscle. To classify the pathogenicity of variants in GAMT, GATM, and SLC6A8, we developed the CCDS Variant Curation Expert Panel (VCEP) in 2018, supported by The Clinical Genome Resource (ClinGen), a National Institutes of Health (NIH)-funded resource. We developed disease-specific variant classification guidelines for GAMT-, GATM-, and SLC6A8-related CCDS, adapted from the American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant interpretation guidelines. We applied specific variant classification guidelines to 30 pilot variants in each of the three genes that have variants associated with CCDS. Our CCDS VCEP was approved by the ClinGen Sequence Variant Interpretation Working Group (SVI WG) and Clinical Domain Oversight Committee in July 2022. We curated 181 variants including 72 variants in GAMT, 45 variants in GATM, and 64 variants in SLC6A8 and submitted these classifications to ClinVar, a public variant database supported by the National Center for Biotechnology Information. Missense variants were the most common variant type in all three genes. We submitted 32 new variants and reclassified 34 variants with conflicting interpretations. We report specific phenotype (PP4) using a points system based on the urine and plasma guanidinoacetate and creatine levels, brain magnetic resonance spectroscopy (MRS) creatine level, and enzyme activity or creatine uptake in fibroblasts ranging from PP4, PP4_Moderate and PP4_Strong. Our CCDS VCEP is one of the first panels applying disease specific variant classification algorithms for an X-linked disease. The availability of these guidelines and classifications can guide molecular genetics and genomic laboratories and health care providers to assess the molecular diagnosis of individuals with a CCDS phenotype.

Longitudinal associations between the frequency of playing Mahjong and cognitive functioning among older people in China: evidence from CLHLS, 2008-2018.

Background: Cognitive decline is prevalent among older adults, often resulting in decreased capabilities for self-care and a diminished quality of life. Mahjong, a culturally cherished and extensively played intellectual game in China, demands considerable cognitive function. While the cognitive benefits of playing Mahjong have been widely accepted, this study investigates an under explored aspect and aimed to ascertain the game's potential contributions toward bolstering self-care abilities, enhancing overall quality of life, and mitigating against rising societal healthcare costs. Methods: The data analyzed in the study is collected from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) with cognitive functioning being assessed through the Mini-Mental State Examination (MMSE). The frequency of playing Mahjong was measured through a self-reported questionnaire. Multiple linear regression models, latent variable growth models, and cross-lagged models were used to investigate the longitudinal relationship between game frequency and cognitive function in older people. Results: Of the 7,535 participants, the mean (SD) age was 81.96 (10.53) years. There were 7,308 (97%), 4,453 (59%), and 1,974 (26%) participants in 2011, 2014, and 2018, respectively. The results showed that Mahjong players had significantly higher MMSE scores compared to non-players from 2008 to 2018 (ß = 0.893; p < 0.001), and non-players had significantly lower scores in 2011, 2014, and 2018 than in 2008 (ß = -1.326, -0.912, -0.833; Ps > 0.05). Moreover, the frequency of playing Mahjong was associated with improved various cognitive domains. The declining frequency of playing Mahjong was substantially associated with the declining rate of MMSE scores (r = 0.336; p < 0.001). Mahjong frequency showed positive effects on MMSE scores, while the influence of Mahjong on MMSE scores were not significant. Conclusion: Playing Mahjong has a positive influence on the cognitive functioning among older people. It can help buffer against the decline in cognitive function and maintain cognitive function levels. The higher frequency of playing Mahjong is associated with improved reaction, attention and calculation, and self-coordination. A decline in the frequency of playing Mahjong was associated with a declining rate of cognitive function. The higher frequency of playing Mahjong among older people unilaterally influenced the improvement of cognitive function levels in older people in China.

Recruitment strategies in marginalized industries for occupational health research: an example in a pilot study of cleaning staff during COVID-19.

This commentary describes challenges in recruiting workers from marginalized industries with examples from a pilot study of janitors, custodians, and maids and their experiences of cleaning and disinfection protocols during COVID-19 and potentially associated respiratory symptoms. Recruitment strategies included contacting a local hospital, national workers' unions, and a large Arizona employer; using online Facebook groups; and contacting Arizona maid service companies and a school district. English and Spanish online and hard copy surveys about cleaning protocols and respiratory symptoms were used. Participants could also participate in online/phone interviews. Worker's compensation, liability, and confidentiality were concerns across organizations. Online surveys yielded unreliable data. Hard copy surveys were used due to workers' limited technology access. We reflect upon these challenges and discuss other strategies for recruiting from marginalized populations for occupational health research. Building trust with organizations and workers and considering technology access may ultimately increase recruitment feasibility.

Transmission of Viruses from Restroom Use: A Quantitative Microbial Risk Assessment.

Restroom use has been implicated in a number of viral outbreaks. In this study, we apply quantitative microbial risk assessment to quantify the risk of viral transmission by contaminated restroom fomites. We estimate risk from high-touch fomite surfaces (entrance/exit door, toilet seat) for three viruses of interest (SARS-CoV-2, adenovirus, norovirus) through eight exposure scenarios involving differing user behaviors, and the use of hand sanitizer following each scenario. We assessed the impacts of several sequences of fomite contacts in the restroom, reflecting the variability of human behavior, on infection risks for these viruses. Touching of the toilet seat was assumed to model adjustment of the seat (open vs. closed), a common touch point in single-user restrooms (home, small business, hospital). A Monte Carlo simulation was conducted for each exposure scenario (10,000 simulations each). Norovirus resulted in the highest probability of infection for all exposure scenarios with fomite surfaces. Post-restroom automatic-dispensing hand sanitizer use reduced the probability of infection for each virus by up to 99.75%. Handwashing within the restroom, an important risk-reduction intervention, was not found to be as effective as use of a non-touch hand sanitizer dispenser for reducing risk to near or below 1/1,000,000, a commonly used risk threshold for comparison.

Hazardous drinking in young adults with co-occurring PTSD and psychosis symptoms: A network analysis.

BACKGROUND: Existing literature suggests the co-occurrence of post-traumatic stress disorder (PTSD) and psychosis among young adults is related to hazardous drinking. However, the influencing mechanisms among these co-occurrences are inconclusive. Thus, this study aimed to investigate the symptomatic associations between PTSD, psychosis, and hazardous drinking. METHODS: This study included 96,218 young Chinese adults, divided into three groups (PTSD, Psychosis, and co-occurring PTSD-Psychosis). PTSD, psychosis, and hazardous drinking were measured by the ten-item Trauma Screening Questionnaire, the seven-item Psychosis Screener Scale, and the four-item Alcohol Use Disorders Identification Test, respectively. Network analysis was utilized to explore and compare the symptomatic correlation between PTSD, psychosis, and hazardous drinking. RESULTS: In this study, the most crucial symptom (both central and bridge) was "delusion of control" among the three networks. Hazardous drinking was another main bridge symptom. Compared to the Psychosis group and the co-occurring PTSD-Psychosis group, "Delusion of reference or persecution" to "Grandiose delusion" was the strongest edge in "the network structure of the PTSD group". LIMITATIONS: The cross-sectional study cannot determine the causal relationship. Applying self-reporting questionnaires may cause inherent bias. Young adult participants limited the generalization of the results to other groups. CONCLUSIONS: Among the three network structures, delusion of control was the most crucial symptom, and hazardous drinking was another bridge symptom; the edge of delusion of reference or persecution and grandiose delusion was strongest in the PTSD group's network. Efforts should be taken to develop diverse targeted interventions for these core symptoms to relieve PTSD, psychosis, and hazardous drinking in young adults.

Mental health recovery in a collectivist society: Saudi consumers, carers and nurses' shared perspectives.

In 2019, the World Health Organization urged a global shift towards recovery-focused practices in mental health care. In Western nations, this transition often prioritised individualism over collectivism. In contrast, collectivist societies prioritise recovery through community and social support. This study explored mental health recovery from the perspectives of consumers, carers and registered nurses in a mainly collectivist society (Saudi Arabia) using a qualitative exploratory descriptive design. Sixteen consumers, ten carers and eight registered nurses participated in online semi-structured interviews. Inductive thematic analysis was employed to analyse English-translated versions of the 34 interviews. Consolidated criteria for reporting qualitative studies 32-item checklist were used. The study found that recovery was perceived as a process of transforming towards living a meaningful life of goals and values supported by trusted people who share moments of comfort and empowerment. A unique finding was the 'bond of recovery' a collectivist value that aid consumers' community integration in society. Saudi consumers' experiences of recovery were similar to consumers' movement narratives of recovery. Future research should establish a recovery-focused educational program that incorporates our findings into a recovery-oriented approach. This will facilitate providing a collaborative care between consumers, carers and nurses that centres around consumers' recovery goals and values.

Human adenovirus-associated health risk in the recreational waters of the Yal-ku lagoon in the Mexican Caribbean.

The study objective was to evaluate human faecal contamination impacts in the Yal-ku lagoon in the Mexican Caribbean and to estimate adenovirus infection and illness risks associated with recreational exposure during water activities. A total of 20 water samples (10 from each site × two sites) (50 L) were collected monthly over a period of 12 months from two selected sampling sites in the swimming area of the Yal-ku lagoon. The occurrence of faecal-associated viruses was explored, and human adenovirus (HAdV) and pepper mild mottle virus (PMMoV) concentrations were quantified. A quantitative microbial risk assessment (QMRA) model was used to estimate exposure and subsequent adenovirus infection and illness risk for 1 h of swimming or snorkelling. Somatic and F + -specific coliphages occurred in 100% of the samples. Both HAdV and PMMoV were detected at a 60% frequency thereby indicating persistent faecal inputs. PMMoV concentrations (44-370 GC/L) were relatively lower than the concentrations of HAdV (64-1,000 GC/L). Estimated mean adenovirus risks were greater for snorkelling than for swimming by roughly one to two orders of magnitude and estimated mean illness risks for snorkelling were >32/1,000. Human faecal contamination is frequent in the Yal-ku lagoon, which is associated with human gastrointestinal illness.

Satisfaction with asynchronous e-learning: An exploratory factor analysis of the Learner Satisfaction with Asynchronous e-Learning (LSAeL) instrument.

AIM: To describe the development and psychometric testing of the Learner Satisfaction with Asynchronous e-Learning (LSAeL) instrument. BACKGROUND: Existing satisfaction with e-learning instruments may not accurately evaluate learner satisfaction with constructs associated with asynchronous e-learning. DESIGN: Methodological study. METHODS: Content, face and construct validity of the instrument were evaluated using a two-stage process. A five-member expert panel evaluated the instrument's content and face validity. A content validity index and a modified kappa co-efficient was used to calculate the content validity of individual test items and the global instrument and to adjust for chance agreement between raters. These data were then reviewed and individual items were removed, retained or refined accordingly. Using an empirically informed wholly asynchronous e-learning program 237 nursing students from a regional university in New South Wales, Australia completed the 35 item LSAeL instrument. An exploratory factor analysis (EFA) was then conducted to explore the dimensionality of the instrument. RESULTS: Exploratory factor analysis identified a seven-factor solution with 30 items, explaining an 86.1% of the total variance, was the best fit for the data. CONCLUSION: The study demonstrates that the construct validity of the LSAeL instrument is acceptable. Instrument development is an iterative process and further testing with other cohorts and in other settings is required.

The influence of childhood trauma and chronotype on suicide attempts in Chinese emerging adults with severe depressive symptoms.

BACKGROUND: Studies have investigated how adults with severe depressive symptoms are more likely to attempt suicide, and these adults often have traumatic experiences and chaotic sleep/wake rhythms. Thus, this study using Latent class analysis aimed to investigate the relationship between childhood trauma class, chronotype, and suicide attempts among emerging adults with severe depressive symptoms. METHODS: This study was conducted among emerging adults with severe depressive symptoms covering 63 Universities in Jilin Province, China. A total of 1,225 emerging adults (mean age = 19.6 ± 1.78) constructed the final sample. In addition to measuring socio-demographic characteristics, the Childhood Trauma Questionnaire-Short Form, the Single-Item Chronotyping, and a single item for suicide attempts were used to evaluate childhood trauma, chronotype, and suicide attempts, respectively. Latent class analysis was applied to identify the classes of childhood trauma within emerging adults who had severe depressive symptoms. Hierarchical logistic regression models were run to investigate the effects of socio-demographic characteristics, chronotype, and childhood trauma class on suicide attempts. RESULTS: Three latent classes were identified: the Low-risk for childhood trauma class, the Neglect class, and the High-risk for childhood abuse class. Those who suffered sexual, emotional, and physical abuse at the same time were divided into the High-risk for childhood abuse class, and were significantly more likely to experience suicide attempts than those in the Neglect class (OR = 1.97, 95%CI = 1.34-2.89, p < 0.001) and the Low-risk for childhood trauma class (OR = 2.28, 95% CI = 1.50-3.46, p < 0.001). In terms of chronotype, the results showed that the chaotic type was a risk factor for suicide attempts when compared with the evening type (OR = 0.46, 95%CI = 0.27-0.78, p < 0.01), the moderately active type (OR = 0.53, 95%CI = 0.31-0.89, p < 0.05), and the daytime type (OR = 0.42, 95%CI = 0.21-0.86, p < 0.05). Overall, the significant risk factors for suicide attempts included being female, living in an urban area, having experienced sexual, emotional, and physical abuse simultaneously, and having a chaotic chronotype. CONCLUSION: Emerging adults suffering sexual, emotional, and physical abuse at the same time and identifying with chaotic chronotype showed a higher risk of attempting suicide. The findings provided a clinical reference to quickly identify those at high risk of suicide attempts among emerging adults with severe depressive symptoms.

Patulin contamination of hard apple cider by Paecilomyces niveus and other postharvest apple pathogens: Assessing risk factors.

Hard apple cider is considered to be a low-risk product for food spoilage and mycotoxin contamination due to its alcoholic nature and associated food sanitation measures. However, the thermotolerant mycotoxin-producing fungus Paecilomyces niveus may pose a significant threat to hard cider producers. P. niveus is known to infect apples (Malus xdomestica), and previous research indicates that it can survive thermal processing and contaminate finished apple juice with the mycotoxin patulin. To determine if hard apple cider is susceptible to a similar spoilage phenomenon, cider apples were infected with P. niveus or one of three patulin-producing Penicillium species and the infected fruits underwent benchtop fermentation. Cider was made with lab inoculated Dabinett and Medaille d'Or apple cultivars, and patulin was quantified before and after fermentation. Results show that all four fungi can infect cider apples and produce patulin, some of which is lost during fermentation. Only P. niveus was able to actively grow throughout the fermentation process. To determine if apple cider can be treated to hinder P. niveus growth, selected industry-grade sanitation measures were tested, including chemical preservatives and pasteurization. High concentrations of preservatives inhibited P. niveus growth, but apple cider flash pasteurization was not found to significantly impact spore germination. This study confirms that hard apple cider is susceptible to fungal-mediated spoilage and patulin contamination. P. niveus is an important concern for hard apple cider producers due to its demonstrated thermotolerance, survival in fermentative environments, and resistance to sanitation measures.

Health-related quality of life of people with heart failure in low- and middle-income countries: a systematic review and meta-analysis.

PURPOSE: Heart failure is a global health concern and associated with poor health-related quality of life and increased mortality. There is a disproportionate burden on patients and health systems in low- and middle-income countries. This systematic review and meta-analysis estimates the health-related quality of life of people with heart failure in low- and middle-income countries. METHODS: A systematic literature search was conducted to identify relevant studies from January 2012 to November 2022 using the following databases: MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science, Scopus and JBI EBP database. Study screening, quality appraisal and data extraction were conducted using JBI methodology. A random-effects model was used to perform the meta-analysis. Heterogeneity was assessed using the I2 statistic. All statistical analyses were done in STATA version 17. RESULTS: A total of 33 studies with 5612 participants were included in this review. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Short-Form-36 questionnaire (SF-36) were the most used instruments across 19 and 8 studies, respectively. The pooled mean MLHFQ and SF-36 scores using the random-effects model were 46.08 (95% CI 35.06, 57.10) and 41.23 (95% CI 36.63, 45.83), respectively. In a subgroup analysis using both instruments, the highest health-related quality-of-life scores occurred in studies with inpatient participants. CONCLUSION: The overall health-related quality of life of people with heart failure in low- and middle-income countries is poor. Strategies should be strategically developed to improve the health-related quality of life of people with heart failure in these countries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022377781.

The diagnostic yield of exome sequencing in liver diseases from a curated gene panel.

Exome sequencing (ES) has been used in a variety of clinical settings but there are limited data on its utility for diagnosis and/or prediction of monogenic liver diseases. We developed a curated list of 502 genes for monogenic disorders associated with liver phenotypes and analyzed ES data for these genes in 758 patients with chronic liver diseases (CLD). For comparison, we examined ES data in 7856 self-declared healthy controls (HC), and 2187 patients with chronic kidney disease (CKD). Candidate pathogenic (P) or likely pathogenic (LP) variants were initially identified in 19.9% of participants, most of which were attributable to previously reported pathogenic variants with implausibly high allele frequencies. After variant annotation and filtering based on population minor allele frequency (MAF ≤ 10-4 for dominant disorders and MAF ≤ 10-3 for recessive disorders), we detected a significant enrichment of P/LP variants in the CLD cohort compared to the HC cohort (X2 test OR 5.00, 95% CI 3.06-8.18, p value = 4.5e-12). A second-level manual annotation was necessary to capture true pathogenic variants that were removed by stringent allele frequency and quality filters. After these sequential steps, the diagnostic rate of monogenic disorders was 5.7% in the CLD cohort, attributable to P/LP variants in 25 genes. We also identified concordant liver disease phenotypes for 15/22 kidney disease patients with P/LP variants in liver genes, mostly associated with cystic liver disease phenotypes. Sequencing results had many implications for clinical management, including familial testing for early diagnosis and management, preventative screening for associated comorbidities, and in some cases for therapy. Exome sequencing provided a 5.7% diagnostic rate in CLD patients and required multiple rounds of review to reduce both false positive and false negative findings. The identification of concordant phenotypes in many patients with P/LP variants and no known liver disease also indicates a potential for predictive testing for selected monogenic liver disorders.

Expectations of duplicate gene retention under the gene duplicability hypothesis.

BACKGROUND: Gene duplication is an important process in evolution. What causes some genes to be retained after duplication and others to be lost is a process not well understood. The most prevalent theory is the gene duplicability hypothesis, that something about the function and number of interacting partners (number of subunits of protein complex, etc.), determines whether copies have more opportunity to be retained for long evolutionary periods. Some genes are also more susceptible to dosage balance effects following WGD events, making them more likely to be retained for longer periods of time. One would expect these processes that affect the retention of duplicate copies to affect the conditional probability ratio after consecutive whole genome duplication events. The probability that a gene will be retained after a second whole genome duplication event (WGD2), given that it was retained after the first whole genome duplication event (WGD1) versus the probability a gene will be retained after WGD2, given it was lost after WGD1 defines the probability ratio that is calculated. RESULTS: Since duplicate gene retention is a time heterogeneous process, the time between the events (t1) and the time since the most recent event (t2) are relevant factors in calculating the expectation for observation in any genome. Here, we use a survival analysis framework to predict the probability ratio for genomes with different values of t1 and t2 under the gene duplicability hypothesis, that some genes are more susceptible to selectable functional shifts, some more susceptible to dosage compensation, and others only drifting. We also predict the probability ratio with different values of t1 and t2 under the mutational opportunity hypothesis, that probability of retention for certain genes changes in subsequent events depending upon how they were previously retained. These models are nested such that the mutational opportunity model encompasses the gene duplicability model with shifting duplicability over time. Here we present a formalization of the gene duplicability and mutational opportunity hypotheses to characterize evolutionary dynamics and explanatory power in a recently developed statistical framework. CONCLUSIONS: This work presents expectations of the gene duplicability and mutational opportunity hypotheses over time under different sets of assumptions. This expectation will enable formal testing of processes leading to duplicate gene retention.