Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease.

Non-coding RNAs (ncRNAs) are RNA molecules that do not code for protein but play key roles in regulating cellular processes. NcRNAs globally affect gene expression in diverse physiological and pathological contexts. Functionally important ncRNAs act in chromatin modifications, in mRNA stabilization and translation, and in regulation of various signaling pathways. Non-alcoholic fatty liver disease (NAFLD) is a set of conditions caused by the accumulation of triacylglycerol in the liver. Studies of ncRNA in NAFLD are limited but have demonstrated that ncRNAs play a critical role in the pathogenesis of NAFLD. In this review, we summarize NAFLD's pathogenesis and clinical features, discuss current treatment options, and review the involvement of ncRNAs as regulatory molecules in NAFLD and its progression to non-alcoholic steatohepatitis (NASH). In addition, we highlight signaling pathways dysregulated in NAFLD and review their crosstalk with ncRNAs. Having a thorough understanding of the disease process's molecular mechanisms will facilitate development of highly effective diagnostic and therapeutic treatments. Such insights can also inform preventive strategies to minimize the disease's future development.

The Characteristics and Outcomes of Nonhospitalized Patients With Heart Failure in Saudi Arabia: A Contemporary Single-Center Study.

Background Contemporary data on patients with heart failure (HF) in Saudi Arabia is limited. Methods This was a retrospective study of patients who were followed in the HF Clinic at our center after January 1, 2022. The study end date was August 31, 2023. Patients who were alive and followed for <6 months were excluded. We reported the clinical characteristics, utilization of established therapies for HF, proportion of potential candidates for ancillary HF treatments, and rates of HF events and mortality. Results A total of 202 patients met the study criteria. The mean age was 56.0 ± 15.2 years. The median follow-up from the initial visit to the study end date was 47 months (interquartile range {IQR}: 29-58 months). Coronary artery disease (CAD) was the cause of HF in 85 (42%) patients. At their latest visit, 103 (51%) patients had diabetes, 82 (41%) were obese, and 134 (66%) received quadruple therapy. Iron deficiency was present in 143 (71%) patients during follow-up. At their latest visit, moderate-to-severe or severe functional mitral regurgitation (MR) and hyperkalemia were present in 15 (7%) and 20 (10%) patients, respectively. The combined annual rate of HF hospitalization and emergency visits for HF was 20%. At least one hospitalization for HF within a year before the study end date occurred in 19 (9%) patients. The annual all-cause mortality was 1.8%. Conclusion This contemporary cohort of outpatients with HF was relatively young and had a high prevalence of diabetes, obesity, and iron deficiency. An estimate of potential candidates for iron replacement, transcatheter repair of the mitral valve, novel potassium binders, and the implantation of the pulmonary artery pressure monitor was among the first reported regionally. All-cause mortality was low, yet the burden of HF-related events was significant.

Percent fluid overload for prediction of fluid de-escalation in critically ill patients in Saudi Arabia: a prospective observational study.

BACKGROUND: Percent fluid overload greater than 5% is associated with increased mortality. The appropriate time for fluid deresuscitation depends on the patient's radiological and clinical findings. This study aimed to assess the applicability of percent fluid overload calculations for evaluating the need for fluid deresuscitation in critically ill patients. METHODS: This was a single-center, prospective, observational study of critically ill adult patients requiring intravenous fluid administration. The study's primary outcome was median percent fluid accumulation on the day of fluid deresuscitation or intensive care unit (ICU) discharge, whichever came first. RESULTS: A total of 388 patients was screened between August 1, 2021, and April 30, 2022. Of these, 100 with a mean age of 59.8±16.2 years were included for analysis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15.4±8.0. Sixty-one patients (61.0%) required fluid deresuscitation during their ICU stay, while 39 (39.0%) did not. Median percent fluid accumulation on the day of deresuscitation or ICU discharge was 4.5% (interquartile range [IQR], 1.7%-9.1%) and 5.2% (IQR, 2.9%-7.7%) in patients requiring deresuscitation and those who did not, respectively. Hospital mortality occurred in 25 (40.9%) of patients with deresuscitation and six (15.3%) patients who did not require it (P=0.007). CONCLUSIONS: The percent fluid accumulation on the day of fluid deresuscitation or ICU discharge was not statistically different between patients who required fluid deresuscitation and those who did not. A larger sample size is needed to confirm these findings.

Molecular epidemiology and outcome of carbapenem-resistant Enterobacterales in Saudi Arabia.

BACKGROUND: The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers. METHODS: This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables. RESULTS: A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26-6.24), p = 0.01]. CONCLUSIONS: These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.

Transhepatic double lumen hemodialysis catheter in exhausted vascular access: Feasibility, functionality, and outcome among hemodialysis patients.

INTRODUCTION: Permanent arteriovenous fistula and graft are considered the best options for hemodialysis in end-stage renal disease patients. Temporary access using the internal jugular or femoral veins is the feasible option in acute cases of dialysis and if permanent access is unavailable. Occasionally, however, these access sites are unusable after consecutive blockage of the upper and lower extremities veins. A transhepatic or translumbar approach might be the only unconventional way to ensure a sufficient blood flow for adequate dialysis. METHOD: Retrospective data on all transhepatic catheters (THCs) in patients at the King Faisal Specialist Hospital and Research Center in Jeddah, Saudi Arabia were collected. The catheters were inserted over a 10-year period (2009-2019). A minimum of 1 year of follow-up from the last catheter insertion was considered for analysis. RESULTS: A total of 12 patients had THCs with a mean age of 42.5 ± 12.2 and pre-insertion mean dialysis duration of 130.0 ± 72.9 months. All catheters were functional from the start with no immediate complications. A total of 35 catheter replacements over guidewires were made with a median of 2.0 catheters (range of 0-10). The mean blood flow was 300 ± 30 ml/minute with a mean Kt/v of 1.4 ± 0.4. The median initial (primary) device service interval was 68 (range 6-1531 days) and the median total access site service interval was 392 (range 76-2698 days). Catheter complications included catheter migration, thrombosis, and bloodstream infection occurring at a rate of 0.12, 0.18, and 0.046 per 100 catheter days respectively. CONCLUSIONS: Transhepatic catheters provide safe, feasible access in patients with exhausted vascular access. Patients who undergo THC insertion should be worked up for innovative permanent vascular access or urgent transplantation utilizing unconventional vascular techniques to avoid death due to lack of access.

Outpatient fractionated ICE protocol in relapsed/refractory lymphomas: Efficacy and safety.

METHODS: In this retrospective trial, we analyzed data of patients with relapsed/refractory lymphoma who received outpatient fractionated ICE between 2011-2017 at a tertiary care center. The three weekly ICE protocol consisted of: ifosfamide 1500 mg/m2 infused over 2 h on days 1-3, carboplatin (5 AUC) on day 1, and etoposide 100 mg/m2 on days 1-3. Rituximab 375 mg/m2 was given to patients with CD20 positive B cell Non-Hodgkin lymphoma. RESULTS: Total of 89 patients were included in this research project. Majority of patients had Hodgkin lymphoma (64%). Mean number of ICE cycles received was 2.5. Complete remission and partial remission rates for primary refractory (62.9%) and non-primary refractory (36.4%) disease were 10.5% and 26.3% versus 41.9% and 29.0% respectively. Event free survival rate was 14.5 months (95% CI 7.7-28.0) and overall survival rate 88.7 months (95% CI 48.1-NR). Grade 3 hematological toxicities were documented in 19.1% of patients with 10.1% experiencing neutropenia and 9% thrombocytopenia. 5.6% had febrile neutropenia. CONCLUSIONS: Our study included, to our knowledge, the largest number of patients treated with outpatient fractionated ICE. Results demonstrated that this regimen might be a reasonable replacement for classic ICE regimen in many patients with lymphoma. It has a favorable safety profile. However, patients with primary refractory lymphomas need more effective regimens.

A single-centre study of genetic mutations, audiology, echocardiogram and pulmonary function in Saudi children with osteogenesis imperfecta.

OBJECTIVES: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited connective tissue disorders, characterised by skeletal fragility. Patients with OI may also exhibit extra-skeletal features like blue or grey scleral colour, fragile skin, easy bruising, joint laxity, short stature, deafness, cardiac valve abnormalities and abnormal pulmonary function. The objective of this study is to describe genetic mutations, prevalence of hearing issues, cardiac complications and impaired pulmonary function in children with OI. METHODS: This is a cross-sectional study of 23 Saudi children aged 6 months to 18 years who were diagnosed with OI. The revised Sillence classification (2,105) was used to classify the OI type. Whole exome sequencing was performed for genetic mutations. The hearing was assessed by either pure-tone audiometry and/or otoacoustic emission testing. Cardiac defects were screened by echocardiograms. Spirometry was performed to assess pulmonary function. Data were analysed with descriptive statistics. RESULTS: Based on the Sillence classification, 16 patients had OI type III, 6 had type IV and 1 had type I. Of the18 patients who had genetic sequencing, 66.6% had autosomal dominant and 33.3% had autosomal recessive mutations. Among children who had screening, hearing loss was diagnosed in 53% (9/17), congenital cardiac malformations in 26% (5/19) and restrictive lung disease in 70% (7/10). CONCLUSIONS: We found significant extra-skeletal features and a high yield of genetic mutations associated with OI. We suggest further studies to develop a screening protocol for extra-skeletal features in children with OI.

Cystic fibrosis gene mutations and polymorphisms in Saudi men with infertility.

BACKGROUND: Some mutations of the cystic fibrosis transmembrane regulator (CFTR) gene may impair spermatogenesis or cause a congenital absence of the vas deferens that manifests as isolated male infertility. OBJECTIVE: Assess the frequency and analyze the spectrum of CFTR gene variations in Saudi men with primary infertility. DESIGN: Prospective, cross-sectional. SETTING: Tertiary care specialist hospital in Jeddah. PATIENTS AND METHODS: Genomic DNA was extracted from peripheral blood samples of Saudi men who presented with primary infertility to the outpatient andrology clinic with either azoospermia or oligoasthenoteratozoospermia. Polymerase chain reaction and direct sequencing were used to identify all variants of the CFTR gene. MAIN OUTCOME MEASURES: Proportion of the patients with a mutant CFTR gene and the spectrum of CFTR gene variations. SAMPLE SIZE: 50 infertile Saudi men. RESULTS: This study identified 10 CFTR gene variants in 7 (14%) subjects (100 chromosomes). The detected variants and polymorphisms were: c.1408G>A, c.4389G>A, c.2562T>G, c.869+11C>T, c.2909-92G>A, c.3469-65C>A, c.1210-6delT, c.1210-6T>A, c.2988+1G>A, and c.1210-13GT>TG. CONCLUSION: We demonstrated that 14% of the study subjects had one or more CFTR mutations and these were compounded in most of the affected patients. The spectrum of CFTR gene mutations in these subjects was similar to the mutations reported in other studies throughout the world. LIMITATIONS: Small sample size and the lack of a control group. CONFLICTS OF INTEREST: None.

Hospitalizations following living donor nephrectomy in the United States.

BACKGROUND AND OBJECTIVES: Living donors represented 43% of United States kidney donors in 2012. Although research suggests minimal long-term consequences of donation, few comprehensive longitudinal studies for this population have been performed. The primary aims of this study were to examine the incidence, risk factors, and causes of rehospitalization following donation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: State Inpatient Databases (SID) compiled by the Agency for Healthcare Research and Quality were used to identify living donors in four different states between 2005 and 2010 (n=4524). Multivariable survival models were used to examine risks for rehospitalization, and patient characteristics were compared with data from the Scientific Registry of Transplant Recipients (SRTR). Outcomes among patients undergoing appendectomy (n=200,274), cholecystectomy (n=255,231), and nephrectomy for nonmetastatic carcinoma (n=1314) were contrasted. RESULTS: The study population was similar to United States donors (for SRTR and SID, respectively: mean age, 41 and 41 years; African Americans, 12% and 10%; women, 60% and 61%). The 3-year incidence of rehospitalization following donation was 11% for all causes and 9% excluding pregnancy-related hospitalizations. After censoring of models for pregnancy-related rehospitalizations, older age (adjusted hazard ratio [AHR], 1.02 per year; 95% confidence interval [95% CI], 1.01 to 1.03), African American race (AHR, 2.16; 95% CI, 1.54 to 3.03), depression (AHR, 1.88; 95% CI, 1.12 to 3.14), hypothyroidism (AHR, 1.63; 95% CI, 1.06 to 2.49), and longer initial length of stay were related to higher rehospitalization rates among donors. Compared with living donors, adjusted risks for rehospitalizations were greater among patients undergoing appendectomy (AHR, 1.58; 95% CI, 1.42 to 1.75), cholecystectomy (AHR, 2.25; 95% CI, 2.03 to 2.50), and nephrectomy for nonmetastatic carcinoma (AHR, 2.95; 95% CI, 2.58 to 3.37). Risks for rehospitalizations were higher among African Americans than whites in each of the surgical groups. CONCLUSIONS: The SID is a valuable source for evaluating characteristics and outcomes of living kidney donors that are not available in traditional transplant databases. Rehospitalizations following donor nephrectomy are less than seen with other comparable surgical procedures but are relatively higher among donors who are older, are African American, and have select comorbid conditions. The increased risks for rehospitalizations among African Americans are not unique to living donation.

Comorbidity burden and perioperative complications for living kidney donors in the United States.

BACKGROUND AND OBJECTIVES: Since 1998, 35% of kidney transplants in the United States have been derived from living donors. Research suggests minimal long-term health consequences after donation, but comprehensive studies are limited. The primary objective was to evaluate trends in comorbidity burden and complications among living donors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The National Inpatient Sample (NIS) was used to identify donors from 1998 to 2010 (n=69,117). Comorbid conditions, complications, and length of stay during hospitalization were evaluated. Outcomes among cohorts undergoing appendectomies, cholecystectomies and nephrectomy for nonmetastatic carcinoma were compared, and sample characteristics were validated with the Scientific Registry of Transplant Recipients (SRTR). Survey regression models were used to identify risk factors for outcomes. RESULTS: The NIS captured 89% (69,117 of 77,702) of living donors in the United States. Donor characteristics were relatively concordant with those noted in SRTR (mean age, 40.1 versus 40.3 years [P=0.18]; female donors, 59.0% versus 59.1% [P=0.13]; white donors, 68.4% versus 69.8% [P<0.001] for NIS versus SRTR). Incidence of perioperative complications was 7.9% and decreased from 1998 to 2010 (from 10.1% to 7.6%). Men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 1.20 to 1.56) and donors with hypertension (AOR, 3.35; 95% CI, 2.24 to 5.01) were more likely to have perioperative complications. Median length of stay declined over time (from 3.7 days to 2.5 days), with longer length of stay associated with obesity, depression, hypertension, and pulmonary disorders. Presence of depression (AOR, 1.08; 95% CI, 1.04 to 1.12), hypothyroidism (AOR, 1.07; 95% CI, 1.04 to 1.11), hypertension (AOR, 1.38; 95% CI, 1.27 to 1.49), and obesity (AOR, 1.07; 95% CI, 1.03 to 1.11) increased over time. Complication rates and length of stay were similar for patients undergoing appendectomies and cholecystectomies but were less than those with nephrectomies for carcinoma. CONCLUSIONS: The NIS is a representative sample of living donors. Complications and length of stay after donation have declined over time, while presence of documented comorbid conditions has increased. Patients undergoing appendectomy and cholecystectomy have similar outcomes during hospitalization. Monitoring the health of living donors remains critically important.

Intimate partner violence victimization and perpetration by Puerto Rican women with severe mental illnesses.

Previous research indicates a higher prevalence of victimization among severely mentally ill women. Few studies have either compared these levels across diagnostic categories or evaluated perpetration by the women. We report qualitative and quantitative findings regarding intimate partner violence perpetrated both against and by a sample of 53 Puerto Rican women diagnosed with major depression, bipolar disorder, or schizophrenia. Interviewers shadowed participants for a period of 2 years. Two-thirds of the women with serious mental illness had histories of victimization. However, 23% of the women also reported histories of violence towards their significant others. This was attributed to various reasons, such as anger, revenge, control, and self-defense. Participants described their personal conceptualization of the violence they received and perpetrated. This has implications for programs designed to prevent family violence, for health care professionals in general, and for psychiatrists, who may be called upon to address future risk of victimization or commission of violence.

Impact of psychiatric and social characteristics on HIV sexual risk behavior in Puerto Rican women with severe mental illness.

BACKGROUND: Latinos in the United States have been identified as a high-risk group for depression, anxiety, and substance abuse. HIV/AIDS has disproportionately impacted Latinos. Review findings suggest that HIV-risk behaviors among persons with severe mental illness (SMI) are influenced by a multitude of factors including psychiatric illness, cognitive-behavioral factors, substance use, childhood abuse, and social relationships. OBJECTIVE: To examine the impact of psychiatric and social correlates of HIV sexual risk behavior in Puerto Rican women with SMI. METHODS: Data collected longitudinally (from 2002 to 2005) in semi-structured interviews and from non-continuous participant observation was analyzed using a cross-sectional design. Bivariate associations between predictor variables and sexual risk behaviors were examined using binary and ordinal logistic regression. Linear regression was used to examine the association between significant predictor variables and the total number of risk behaviors the women engaged in during the 6 months prior to baseline. RESULTS: Just over one-third (35.9%) of the study population (N = 53) was diagnosed with bipolar disorder and GAF scores ranged from 30 to 80 with a median score of 60. Participants ranged in age from 18 to 50 years (M = 32.6 ± 8.7), three-fourths reported a history of either sexual or physical abuse or of both in childhood, and one-fourth had abused substances in their lifetimes. Bivariate analyses indicated that psychiatric and social factors were differentially associated with sexual risk behaviors. Multivariate linear regression models showed that suffering from increased severity of psychiatric symptoms and factors and living below the poverty line are predictive of engagement in a greater number of HIV sexual risk behaviors. PRACTICAL IMPLICATIONS: Puerto Rican women with SMI are at high risk for HIV infection and are in need of targeted sexual risk reduction interventions that simultaneously address substance abuse prevention and treatment, childhood abuse, and the indirect effects associated with SMI such as living in poverty. Mental health programs should address risk behavior among adults with SMI in the context of specific symptomatology and comorbidities.

Comparing two approaches to acquiring HIV-risk data from Puerto Rican women with severe mental illness.

Renewed interest has been expressed by researchers in mixed-method assessment that employs both quantitative and qualitative techniques in an expansive style that utilizes a variety of tactics to address research questions. Participants consisted of Puerto Rican women with severe mental illness living in Cuyahoga County, Ohio. The women were shadowed over a 2-year period to observe and verify behaviors that were self-reported using standardized instruments in semi-structured interviews. Concurrent criterion-related validity was employed to determine the extent of the correlation between responses obtained from the two approaches. Forty-four percent of the women were diagnosed with major depression and the mean overall GAF score was 58.5 +/- 14.5. A comparison of the data collected using the different methodologies revealed that inconsistent and contradictory responses are not uncommon. The mixed-method design provided a more complete way of obtaining HIV-risk behavior data. Researchers and clinicians could benefit from mixed methods research that can provide greater opportunities to obtain data of a sensitive nature.

Social closeness increases salivary progesterone in humans.

We examined whether interpersonal closeness increases salivary progesterone. One hundred and sixty female college students (80 dyads) were randomly assigned to participate in either a closeness task with a partner versus a neutral task with a partner. Those exposed to the closeness induction had higher levels of progesterone relative to those exposed to the neutral task. Across conditions, progesterone increase one week later predicted the willingness to sacrifice for the partner. These results are discussed in terms of the links between social contact, stress, and health.

How to play to your strengths.

Most feedback accentuates the negative. During formal employee evaluations, discussions invariably focus on "opportunities for improvement," even if the overall evaluation is laudatory. No wonder most executives--and their direct reports--dread them. Traditional, corrective feedback has its place, of course; every organization must filter out failing employees and ensure that everyone performs at an expected level of competence. But too much emphasis on problem areas prevents companies from reaping the best from their people. After all, it's a rare baseball player who is equally good at every position. Why should a natural third baseman labor to develop his skills as a right fielder? This article presents a tool to help you understand and leverage your strengths. Called the Reflected Best Self (RBS) exercise, it offers a unique feedback experience that counterbalances negative input. It allows you to tap into talents you may or may not be aware of and so increase your career potential. To begin the RBS exercise, you first need to solicit comments from family, friends, colleagues, and teachers, asking them to give specific examples of times in which those strengths were particularly beneficial. Next, you need to search for common themes in the feedback, organizing them in a table to develop a clear picture of your strong suits. Third, you must write a self-portrait--a description of yourself that summarizes and distills the accumulated information. And finally, you need to redesign your personal job description to build on what you're good at. The RBS exercise will help you discover who you are at the top of your game. Once you're aware of your best self, you can shape the positions you choose to play--both now and in the next phase of your career.