Characterising the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases.

The etiology of prostate cancer, the second most common cancer in men globally, has a strong heritable component. While rare coding germline variants in several genes have been identified as risk factors from candidate gene and linkage studies, the exome-wide spectrum of causal rare variants remains to be fully explored. To more comprehensively address their contribution, we analysed data from 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline exome/genome sequencing and one cohort with imputed array data from a population enriched in low-frequency deleterious variants. Our gene-level collapsing analysis revealed that rare damaging variants in SAMHD1 as well as genes in the DNA damage response pathway ( BRCA2 , ATM and CHEK2 ) are associated with the risk of overall prostate cancer. We also found that rare damaging variants in AOX1 and BRCA2 were associated with increased severity of prostate cancer in a case-only analysis of aggressive versus non-aggressive prostate cancer. At the single-variant level, we found rare non-synonymous variants in three genes ( HOXB13 , CHEK2 , BIK ) significantly associated with increased risk of overall prostate cancer and in four genes ( ANO7 , SPDL1 , AR , TERT ) with decreased risk. Altogether, this study provides deeper insights into the genetic architecture and biological basis of prostate cancer risk and severity.

Health Literacy Among University Students in the COVID-19 Pandemic: A Systematic Review.

BACKGROUND: The purpose of this systematic review was to assess different studies that worked on university students' health literacy during covid19 pandemic and to make an overview of this issue to recognize possible determinants associated with health literacy. METHODS: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Four databases (Google Scholar, Web of Science, Pubmed, and Scopus) were used for searching cross-sectional works that assessed the health literacy of university students. We searched papers from December 1st, 2019 up to June 10th, 2022. English language articles were used. Studies were done in countries including; Iran, Pakistan, the USA, Vietnam, China, Colombia, Germany, and Indonesia. RESULTS: The systematic review contains 12 research studies involving 17773 students. There was a relationship between health literacy and some determinants. Positive determinants included age, female gender, Urban background, cognitive maturity, Higher educational qualification, information source (Health workers), number of semesters, and parental education. Some negative determinants were male gender, Rural background, smoking, drinking, being able to pay for medication, lower conspiracy beliefs, and higher fear of COVID-19. CONCLUSION: University students around the world should have courses about health literacy according to university disciplines. These courses should be available for students of different fields to enhance their effectiveness, and training should be associated with students' needs and their subgroup traits.

Potential Association Between Latent Toxoplasma gondii Infection and Suicide Attempts: A Case-Control Registry-Based Study.

Toxoplasma gondii is a ubiquitous parasitic protozoan that may be an important cause of neurological and psychiatric diseases. The purpose of this case-control registry-based study was to evaluate the prevalence of T. gondii infection and related risk factors among subjects who attempted suicide by drug use and a control group at the Iranian National Registry Center for Toxoplasmosis in Mazandaran Province, northern Iran. Baseline data were collected from participants using a questionnaire, and a blood sample was taken from each individual. The plasma was prepared for serological analysis, whereas the buffy coat was used for molecular analysis. Out of 282 individuals (147 cases with suicide attempters [SA] and 135 controls), 42.9% of patients and 16.3% of control subjects were positive for anti-Toxoplasma immunoglobin G (IgG), but all participants were negative for T. gondii DNA and anti-Toxoplasma immunoglobin M. Based on multiple logistic regressions, IgG seropositivity in SA in the age group of 20-30 years was 3.22 times higher than that in the control group (p < 0.001). These findings suggest that latent T. gondii infection among SA is significantly higher than that in healthy individuals, indicating a potential association between latent toxoplasmosis and SA at least in the studied area. Further research is needed to shed light on the potential association between T. gondii and suicide among different populations and areas of the world.

Relationship between resilience and self-efficacy among Iranian nurses: a cross-sectional study during the post-Corona era.

BACKGROUND: Resilience and self-efficacy play an influential role in nurses' clinical performance, which are considered resources for improving adaptability and promoting work engagement. This study aimed to determine the relationship between resilience and self-efficacy among nurses at Shahroud University of Medical Sciences hospitals during the post-Corona era. METHODS: This cross-sectional study was conducted on 280 nurses in all clinical departments. Nurses with a bachelor of science in nursing or higher degree and at least one year of full-time work experience were included in the study using a convenience sampling method. Participants completed a three-part tool, which included the demographic information form, the Connor-Davidson Resilience Scale, and the General Self-Efficacy Scale. The data were analyzed using descriptive statistics and inferential tests (multivariate linear regression using the backward method). RESULTS: In this study, nurses reported low levels of resilience (63.64 ± 15.66) and high levels of self-efficacy (63.01 ± 9.57). Among the five resilience subscales, the highest mean item score was associated with "spiritual influences" (2.80 out of 4), while the lowest mean item score was associated with "trust in one's instincts and tolerance of negative affect" (2.36 out of 4). Furthermore, the multivariate linear regression model results indicated that self-efficacy accounted for 33.6% of the variance in resilience (P < 0.001 and ß = 0.952). CONCLUSION: According to the results of the present study, it is suggested that nurses' psychological capabilities, such as self-efficacy, should be increased to improve resilience and address the stressful conditions of the work environment.

Relationship between academic procrastination, self-esteem, and moral intelligence among medical sciences students: a cross-sectional study.

BACKGROUND: Academic procrastination is a widespread phenomenon among students. Therefore, evaluating the related factors has always been among the major concerns of educational system researchers. The present study aimed to determine the relationship of academic procrastination with self-esteem and moral intelligence in Shahroud University of Medical Sciences students. METHODS: This cross-sectional descriptive-analytical study was conducted on 205 medical sciences students. Participants were selected based on inclusion and exclusion criteria using the convenience sampling technique. The data collection tools included a demographic information form, Solomon and Rothblum's Procrastination Assessment Scale-Students, Rosenberg Self-Esteem Scale, and Lennick and Kiel's Moral Intelligence Questionnaire, all of which were completed online. The data were analyzed using descriptive statistics and inferential tests (multivariate linear regression with backward method) in SPSS software. RESULTS: 96.1% of participating students experienced moderate to severe levels of academic procrastination. Based on the results of the backward multivariate linear regression model, the variables in the model explained 27.7% of the variance of academic procrastination. Additionally, self-esteem (P < 0.001, ß=-0.942), grade point average (P < 0.001, ß=-2.383), and interest in the study field (P = 0.006, ß=-1.139) were reported as factors related to students' academic procrastination. CONCLUSION: According to the findings of this study, the majority of students suffer from high levels of academic procrastination. Furthermore, this problem was associated with low levels of self-esteem, grade point average, and interest in their field of study.

Genotypic Frequency of Rh Cw Antigen in Blood Donors of Northern Pakistan.

OBJECTIVE: To determine the genotypic frequency of Rh Cw antigen in blood donors of Northern Pakistan. STUDY DESIGN: Descriptive cross-sectional study. Place and Duration of the Study: Department of Molecular Haematology, Armed Forces Institute of Transfusion (AFIT), Rawalpindi, Pakistan, from August 2022 to January 2023. METHODOLOGY: Blood donors were randomly selected. Venous blood samples were taken in K3-EDTA anticoagulant tubes. ABO and Rh D grouping were performed conventionally. DNA for Rh Cw genotyping was extracted via Chelex TM, followed by PCR amplification using an ABI 2700 thermal cycler. Human growth hormone (HGH) acts as an internal control. Amplified products underwent Polyacrylamide gel Electrophoresis (PAGE). RESULTS: There were 400 randomly chosen donors whose ages ranged from 26-35 years, with a predominantly male population (94.8%) of Punjabi origin (67.8%). The majority (87.3%) was RhD positive. Blood group B was the most prevalent (35%) in the studied population, followed by O (34.75%). Only 1.5% had Rh Cw antigen. Rh Cw was more prevalent in ABO-positive participants (87.25%) compared to ABO-negative (12.75%). CONCLUSION: There was a 1.5% prevalence of Rh Cw antigen genotype in randomly selected Northern Pakistani blood donors. Rh Cw prevalence was higher in ABO-positive participants. Significant correlation (<0.05) existed between RhD and Cw antigens. Given the implications of anti-Cw antibody, including Cw antigen-positive cells in antibody screening is recommended. KEY WORDS: Alloimmunisation, Blood donors, HDFN, Phenotype, Rh antigens, Transfusion.

The Effects of Coenzyme Q10 on Contrast-Induced Acute Kidney Injury in Type 2 Diabetes: A Randomized Clinical Trial.

Contrast-induced acute kidney injury (CI-AKI) is a frequent challenge following the injection of contrast media and its subsequent oxidative stress. The aim of the present study was to evaluate the preventive effects of coenzyme Q10 (Q10), as a mitochondrial-targeted antioxidant in CI-AKI in diabetic patients, who account for a large proportion of angiographic cases. A total of 118 diabetic patients were randomly assigned to receive 120 mg of oral coenzyme Q10 (Q10 group) or placebo (Placebo group) for four days, starting 24 hours before contrast media injection. Blood urea nitrogen (BUN), serum and urinary creatinine, estimated glomerular filtration rate (eGFR), urinary malondialdehyde (UMDA), urinary total antioxidant capacity (UTAC), and urinary mitochondrial to nuclearDNA ratios (mtDNA/nDNA ratio) were evaluated before and after the treatment period. Urine sediments were also evaluated to report the urine microscopy score (UMS).The levels of BUN, serum and urine creatinine, and UMS were similar in the Q10 and placebo groups. EGFR was lower in the Q10 group before the treatment (p=0.013) but not after. The urinary mtDNA/nDNA ratio was 3.05±1.68 and 3.69±2.58 in placebo and Q10 groups, but UTAC was found to be lower in Q10 both before (p=0.006) and after the treatment (p<0.001). The incidence of CI-AKI was 14.40% and the mtDNA/nNDA ratio was similar between CI-AKI and non-CI-AKI patients. In conclusion, Q10 treatment shows no favorable effect on prevention of CI-AKI or a urinary mtDNA/nDNA ratio among diabetic patients.

Precision Oncology in Breast Cancer Surgery.

Outcomes for patients with breast cancer have improved over time due to increased screening and the availability of more effective therapies. It is important to recognize that breast cancer is a heterogeneous disease that requires treatment based on molecular characteristics. Early endpoints such as pathologic complete response correlate with event-free survival, allowing the opportunity to consider de-escalation of certain cancer treatments to avoid overtreatment. This article discusses clinical trials of tailoring treatment (eg, I-SPY2) and screening (eg, WISDOM) to individual patients based on their unique risk features.

The effect of spiritual reminiscence therapy on depression and hope among Iranian older adults: a quasi-experimental study.

This quasi-experimental study aimed to evaluate the impact of spiritual reminiscence therapy (SRT) on depression and hope among older adults living in Shahroud, northeast of Iran. One hundred fifty-six older adults were selected through convenience sampling and assigned non-randomly to the intervention (n= 78) and control (n= 78) groups. The data collection tools included the Geriatric Depression Scale and Adult Hope Scale. For the intervention group, SRT was conducted in six weekly sessions, each lasting 60 to 90 min, over six weeks. The data were analyzed utilizing descriptive statistics and inferential tests (independent t-test, Chi-square test, and analysis of covariance). The two groups' post-intervention mean scores on depression (t= 11.63 and P< 0.001), and hope (t= 4.41 and P< 0.001) were statistically different, suggesting that SRT positively affected older adults by alleviating despair and boosting hope. The findings indicate that engaging in SRT can be beneficial in reducing depression and fostering hope among older adults.

Vision-related quality of life in patients with retinal vein occlusion.

PURPOSE: This study aims to assess the vision-related quality of life in patients with retinal vein occlusion (RVO) among those referred to Labbafinejad Medical Center and Imam Hossein Hospital between 2019 and 2021. METHODS: This comparative study included 37 eligible patients diagnosed with various types of RVO, with an average age of 61 ± 9. To ensure data validity, we included 74 age- and sex-matched healthy individuals. Only cases with a definitive diagnosis of RVO, confirmed by two retina specialists (ND and RN), were included. We assessed the vision-related quality of life of our participants using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). All participants underwent interviews. RESULTS: In our study, we examined the vision-related quality of life in different subgroups of RVO patients. Overall, RVO patients had a significantly lower total VRQoL score compared to healthy individuals (P < 0.001), except in the subscale analysis of specific factors such as ocular pain, color vision, and driving, where no statistically significant difference was observed. A statistically significant difference was found in the comparison of subgroups, indicating lower VRQoL in central retinal vein occlusion (CRVO) patients (P = 0.010). Furthermore, a significant correlation was observed between lower VRQoL and decreased vision (P = 0.009) as well as longer disease duration (P = 0.011). CONCLUSION: Retinal vein occlusion can significantly reduce vision-related quality of life, particularly in more severe cases.

Mini review: human clinical studies of stem cell therapy in keratoconus.

Treatment of keratoconus is one of the most interesting research fields for researchers in the world. Regenerative medicine based on human stem cells in the treatment of keratoconus has recently received attention. Despite extensive laboratory and animal studies in regenerative medicine of cornea, there are limited clinical studies in keratoconus. These studies showed promising results of stem cell therapy. In initial studies, the transplantation of these cells into stroma was associated with increased vision and improved corneal parameters without side effects. In this article, we tried to review different aspects of keratoconus stem cell therapy, including cell extraction and culture, surgical procedure, effectiveness and safety of this method in human clinical studies.

Psychometric evaluation of the Persian version of the Sense of Belonging in Nursing School (SBNS): a quantitative and cross-sectional design.

BACKGROUND: This study aimed to evaluate the psychometric indicators of the Persian version of the Sense of Belonging in Nursing School scale (SBNS). METHODS: The study conducted in Shahroud and Semnan schools of nursing and midwifery in Iran examined nursing students using a cross-sectional approach by convenience sampling method from 3/6/2023 to 24/8/2023. To assess the SBNS scale, the forward-backward procedure was used to translate it into Persian. Face and content validity were evaluated, and exploratory and confirmatory factor analyses were conducted with sample sizes of 200 and 182, respectively. Reliability was assessed using Cronbach's alpha coefficient, MacDonald's omega, and intra-class correlation coefficient. RESULTS: The exploratory factor analysis resulted in the exclusion of four items, leaving a final selection of 15 items. These items were categorized into three factors: classmates, clinical staff, and inclusive educational environment, which accounted for 49.16% of the overall variance. The confirmatory factor analysis indicated that the model was a good fit for the observed data, and the subscales had high internal consistency (Cronbach's alpha coefficient was 0.752 to 0.880) and stability (intra-class correlation coefficient was 0.889 to 0.968). CONCLUSION: According to the results, it can be concluded that the Persian version of the SBNS scale demonstrates sufficient validity and reliability in assessing students' sense of belonging to the nursing school.

Using an expanded algorithm to estimate prevalence of amyotrophic lateral sclerosis in U.S. and UK.

BACKGROUND: There is an increasing need to better understand the burden of amyotrophic lateral sclerosis (ALS) using real-world data (RWD). However, identifying ALS cases using RWD presents several challenges due to the rarity of ALS and the differences in database coding systems. METHODS: MarketScan claims, and the UK Clinical Practice Research Datalink (CPRD) databases were searched for diagnosis codes of ALS or MND, the only drugs approved for treating ALS (riluzole and edaravone) and clinical visits with 12-month enrolment prior to 1 January 2011. The main algorithm required ≥ 1 ALS diagnosis code together with prescriptions or clinical visits. We expanded the existing algorithm to identify unspecific (possible) ALS group that had codes for motor neuron disease (MND) and the ALS drugs. The study period was from 1 January 2011 until 31 December 2020. RESULTS: We identified 16,246 patients with ≥ 1 ALS code in Marketscan (denominator n = 85,279,619), yet only 184 were found in the UK CPRD (denominator n = 21,318,589). Using the main algorithm 9,433 ALS patients were included in MarketScan, with a prevalence ranged between 4.5 per 100,000 in 2019 and 6.2 in 2015. In MarketScan, 3,658 (4.3 per 100,000) had ≥ 1 MND code and the ALS drug codes (possible cases). In CPRD, 47.9% of 2,785 patients with ≥ 1 MND code had a prescription for riluzole (6.3 per 100,000), regarded as possible ALS cases. CONCLUSIONS: The expanded algorithm enabled the identification of a large population with ALS, or possible ALS, and the estimation of ALS prevalence in MarketScan and CPRD.

Why some Patients Benefit from Participating in a Sham Surgery Trial.

OBJECTIVE: We analyze the ethics of sham surgical trials from a utilitarian perspective and explore whether patients can benefit from participating in these trials. BACKGROUND: Sham-controlled randomized trials are an essential tool to evaluate the risks and benefits of some surgical procedures. However, sham trials are controversial because they expose patients to the harms of a sham procedure without the possibility of benefit. We argue that ethical analyses of sham trials have focused only on the harms of sham surgery and neglected to account for the harms of the procedure being studied. METHODS: We develop a theoretical model to estimate the harms and benefits experienced by patients who enter a sham surgery trial, taking into account the harms and benefits of the sham and intervention. RESULTS: When the procedure in question is found to be ineffective, sham trials typically result in a net benefit to participants because some participants are only exposed to the harms of the sham procedure, which are much lower than the harms of the full procedure. When the procedure is found to be beneficial, the primary harm to patients who underwent the sham is not due to the sham itself but because they suffer a delay in receiving an effective intervention. CONCLUSIONS: Patients often benefit from participating in sham surgery trials because the harms of the sham procedure are lower than the harms of the full procedure, which may turn out to be ineffective. Our results call for re-thinking the ethics of sham surgery trials.

Fatal peritonitis due to gastric perforation in a male heroin addict: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Perforation of hollow organs, such as the stomach, within the abdomen can lead to the development of acute abdomen, a critical and potentially life-threatening condition. It is important to note that there is currently insufficient information available regarding the specific effects of heroin, an illegal substance commonly abused, in causing this particular complication. CASE PRESENTATION: We present the case of a 32-year-old male who is addicted to heroin and was admitted to an addiction rehabilitation center with the aim of overcoming his addiction. After a few days of admission, the patient developed symptoms of abdominal pain, anorexia, and subsequent neurological manifestations, such as drowsiness, confusion, and a decreased level of consciousness. Tragically, the patient suffered a cardiorespiratory arrest upon arrival at the emergency room and despite efforts to resuscitate him, he unfortunately passed away. CLINICAL DISCUSSION: During the autopsy of the aforementioned case, an observation was made of a perforation in the stomach, which ultimately led to the cause of death being identified as peritonitis. Acute peritonitis is recognized as one of the potential causes of acute abdomen, often resulting from the rupture of hollow organs within the abdominal region. It is characterized by inflammation of the serous membrane that lines the abdominal cavity. CONCLUSIONS: Indeed, conducting original and coherent studies to investigate the potential effects of heroin on gastric perforation could prove to be highly valuable in facilitating the timely diagnosis and treatment of this fatal complication.

Alamandine injection in the periaqueductal gray and rostral ventromedial medulla attenuates allodynia induced by sciatic nerve ligation in rats.

Alamandine, a peptide known to interact with Mas-related G protein-coupled receptor subtype D (MrgD), has been implicated in moderating inflammatory signals. MrgD receptors are abundantly found in pain transmission pathways, but the role of alamandine/MrgD in pain modulation has not been thoroughly explored. This study aimed to investigate the effects of alamandine (10, 40, and 100 pmol) in a rat model of allodynia induced by sciatic nerve ligation, with a specific focus on examining the involvement of MrgD receptors, NMDAR1, and serotonin transporter (SERT) in the ventrolateral periaqueductal gray (vlPAG) and rostral ventromedial medulla (RVM). Microinjection of alamandine into the vlPAG at a dose of 100 pmol and into the RVM at doses of 40 and 100 pmol resulted in a significant increase in paw withdrawal threshold (PWT). Additionally, co-administration of D-Pro7-Ang-(1-7) at 50 pmol, an MrgD receptor antagonist, effectively blocked the analgesic effects of alamandine. Immunofluorescence analysis confirmed the presence of MrgD receptors in both the vlPAG and RVM regions. Importantly, an upregulation of MrgD receptor expression was observed following allodynia induction, suggesting a potential compensatory mechanism in response to pain. Our findings support the co-localization of MrgD receptors with NMDAR1 in vlPAG neurons, suggesting their ability to initiate analgesic pathways similar to those activated by NMDA receptors in the vlPAG. Furthermore, our results underscore a significant co-localization of MrgD receptors with the SERT in the RVM, underscoring their potential impact on serotonergic neurons involved in promoting analgesic effects.

An Attention-based Bidirectional LSTM Model for Continuous Cross-Subject Estimation of Knee Joint Angle during Running from sEMG Signals.

Accurate and robust estimation of joint kinematics via surface electromyogram (sEMG) signals provides a human-machine interaction (HMI)-based method that can be used to adequately control rehabilitation robots while performing complex movements, such as running, for motor function restoration in affected individuals. To this end, this paper proposes a deep learning-based model (AM-BiLSTM) that integrates a bidirectional long short-term memory (BiLSTM) network and an attention mechanism (AM) for robust estimation of joint kinematics. The proposed model was appraised using knee joint kinematic and sEMG signals collected from fourteen subjects who performed running at the speed of 2 m/s. The proposed model's generalizability was tested for both within- and cross-subject scenarios and compared with long short-term memory (LSTM) and multi-layer perceptron (MLP) networks in terms of normalized root-mean-square error and correlation coefficient metrics. Based on the statistical tests, the proposed AM-BiLSTM model significantly outperformed the LSTM and MLP methods in both within- and cross-subject scenarios (p<0.05) and achieved state-of-the-art performance.Clinical Relevance- The promising results of this study suggest that the AM-BiLSTM model has the potential for continuous cross-subject estimation of lower limb kinematics during running, which can be used to control sEMG-driven exoskeleton robots oriented towards rehabilitation training.

Effects of Increased Blood Flow Rate and Oral Activated Charcoal on the Severity of Uremic Pruritus: A Randomized Crossover Clinical Trial.

The aim of this study was to compare the effect of increased blood flow rate and the administration of an activated charcoal suspension on the severity of uremic pruritus in hemodialysis patients in a crossover clinical trial. Each group (n = 20) received three 2-week interventions, including increased pumping speed, daily administration of a charcoal suspension (6 g), and the concurrent use of increased pumping speed and oral administration of the charcoal suspension. After each intervention, they had a 2-week washout period. The severity and quality of pruritus were measured using the Yosipovitch's pruritus questionnaire. The results showed that the mean severity, highest pruritus score, and lowest pruritus score decreased after all three interventions, but the highest decrease was related to the third intervention. Considering the results of this study, simultaneous use of increased pumping speed and oral administration of a charcoal suspension is recommended to reduce uremic pruritus in hemodialysis patients.

Effects of rowing stroke rates on lower extremity intra-joint coordination variability in experienced young rowers.

The purpose of this study was to examine the effects of rowing stroke rates on lower extremity intra-joint coordination variability in professional rowers. Fifteen experienced young rowers volunteered to participate in this study. Kinematic data were recorded at different rowing speeds with seven Vicon cameras. The continuous relative phase (CRP) and CRP variability (CRPV) were used to calculate joint coordination and coordination variability, respectively, for the hip, knee, and ankle in the sagittal and horizontal planes, and a comparison was made among different rowing stroke rates. A vector analysis repeated measure ANOVA using statistical parametric mapping revealed that there were statistically significant differences in the hip-ankle, hip-knee, and knee-ankle CRPs for rowing at different stroke rates. Moreover, there was higher CRPV in the mid-drive and mid-recovery phases and less variability in the transition from the drive phase to the recovery phase. The results demonstrate the importance of knee joint in rowing tasks in experienced rowers during submaximal rowing stroke rate and the shift of movement to the hip at higher rowing stroke rate. Moreover, there was a smaller variability during drive-to-recovery transition, which may suggests an increased risk for overuse injuries.