Unveiling Drivers of Retinal Degeneration in RCS Rats: Functional, Morphological, and Molecular Insights.

Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, significantly contribute to adult blindness. The Royal College of Surgeons (RCS) rat is a well-established disease model for studying these dystrophies; however, molecular investigations remain limited. We conducted a comprehensive analysis of retinal degeneration in RCS rats, including an immunodeficient RCS (iRCS) sub-strain, using ocular coherence tomography, electroretinography, histology, and molecular dissection using transcriptomics and immunofluorescence. No significant differences in retinal degeneration progression were observed between the iRCS and immunocompetent RCS rats, suggesting a minimal role of adaptive immune responses in disease. Transcriptomic alterations were primarily in inflammatory signaling pathways, characterized by the strong upregulation of Tnfa, an inflammatory signaling molecule, and Nox1, a contributor to reactive oxygen species (ROS) generation. Additionally, a notable decrease in Alox15 expression was observed, pointing to a possible reduction in anti-inflammatory and pro-resolving lipid mediators. These findings were corroborated by immunostaining, which demonstrated increased photoreceptor lipid peroxidation (4HNE) and photoreceptor citrullination (CitH3) during retinal degeneration. Our work enhances the understanding of molecular changes associated with retinal degeneration in RCS rats and offers potential therapeutic targets within inflammatory and oxidative stress pathways for confirmatory research and development.

Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry.

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring's health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients.

Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Induced Carcinogenesis and Tumorigenesis by Omega-3 Fatty Acids in Mice In Vivo.

Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC. Adult wild-type (WT) (A/J) mice, Cyp1a1-null, Cyp1a2-null, or Cyp1b1-null mice were exposed to PAHs benzo[a]pyrene (BP) or 3-methylcholanthrene (MC), and the effects of omega-3 fatty acid on PAH-mediated lung carcinogenesis and tumorigenesis were studied. The major findings were as follows: (i) omega-3 fatty acids significantly decreased PAH-DNA adducts in the lungs of each of the genotypes studied; (ii) decreases in PAH-DNA adduct levels by EPA/DHA was in part due to inhibition of CYP1B1; (iii) inhibition of soluble epoxide hydrolase (sEH) enhanced the EPA/DHA-mediated prevention of pulmonary carcinogenesis; and (iv) EPA/DHA attenuated PAH-mediated carcinogenesis in part by epigenetic mechanisms. Taken together, our results suggest that omega-3 fatty acids have the potential to be developed as cancer chemo-preventive agents in people.

The Influence of Microglia on Neuroplasticity and Long-Term Cognitive Sequelae in Long COVID: Impacts on Brain Development and Beyond.

Microglial cells, the immune cells of the central nervous system, are key elements regulating brain development and brain health. These cells are fully responsive to stressors, microenvironmental alterations and are actively involved in the construction of neural circuits in children and the ability to undergo full experience-dependent plasticity in adults. Since neuroinflammation is a known key element in the pathogenesis of COVID-19, one might expect the dysregulation of microglial function to severely impact both functional and structural plasticity, leading to the cognitive sequelae that appear in the pathogenesis of Long COVID. Therefore, understanding this complex scenario is mandatory for establishing the possible molecular mechanisms related to these symptoms. In the present review, we will discuss Long COVID and its association with reduced levels of BDNF, altered crosstalk between circulating immune cells and microglia, increased levels of inflammasomes, cytokines and chemokines, as well as the alterations in signaling pathways that impact neural synaptic remodeling and plasticity, such as fractalkines, the complement system, the expression of SIRPα and CD47 molecules and altered matrix remodeling. Together, these complex mechanisms may help us understand consequences of Long COVID for brain development and its association with altered brain plasticity, impacting learning disabilities, neurodevelopmental disorders, as well as cognitive decline in adults.

Applicability of a Chemiluminescence Immunoassay to Screen Postmortem Bile Specimens and Its Agreement with Confirmation Analysis.

Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children. Toxicological investigation consists in screening and, subsequently, confirming the result with specific techniques, such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). As there is no screening test on the market to test postmortem bile specimens, the novelty of this study was in investigating the applicability of a chemiluminescence immunoassay, designed for other matrices and available on the market, on bile and validate its use, testing the agreement with LC-MS/MS analysis. Bile specimens were obtained from 25 forensic cases of suspected death from overdose and intoxication. Sample preparation for bile screening consists simply in centrifugation and dilution. Confirmation analysis allows simultaneous identification of 108 drugs and was validated on bile. Kappa analysis assessed a perfect agreement (0.81-1) between the assays for benzodiazepines, methadone, opiates, cocaine, oxycodone, cannabinoids, buprenorphine and pregabalin; a substantial agreement (0.41-0.6) was reported for barbiturates. No agreement was assessed for amphetamines, due to an abundance of putrefactive amines in postmortem specimens. In conclusion, this fast and easy immunoassay could be used for initial screening of bile specimens, identifying presence of drugs, except amphetamines, with reliability.

Association between Intracellular Calcium Signaling and Tumor Recurrence in Human Non-Functioning Pituitary Adenomas.

Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by the absence of hormonal hypersecretion syndrome, and patients present with compressive symptoms, such as a headache and visual field defects. Immunohistochemically, most CNFPAs are of gonadotrope differentiation, with only a few of them being truly null cell adenomas. Although these tumors express receptors for one or more hypothalamic releasing hormones, to what extent this has an impact on the biological and clinical behavior of these neoplasms remains to be defined. In this research, we evaluated the basal and hypothalamic secretagogue-stimulated intracellular calcium mobilization in 13 CNFPAs, trying to correlate this response to the phenotypic features of the patients. Our results indicate that the recurrence of a CNFPA correlates positively with cellular responsiveness, as measured by spontaneous intracellular calcium activity and the ability to respond to multiple hypothalamic secretagogues. We conclude that this finding may be a useful tool for predicting the clinicopathologic behavior of CNFPAs, by testing the variation of cellular responsiveness to hypothalamic secretagogues.

SLAM Family Receptors in B Cell Chronic Lymphoproliferative Disorders.

The signaling lymphocytic activation molecule (SLAM) receptor family (SLAMF) consists of nine glycoproteins that belong to the CD2 superfamily of immunoglobulin (Ig) domain-containing molecules. SLAMF receptors modulate the differentiation and activation of a wide range of immune cells. Individual SLAMF receptors are expressed on the surface of hematopoietic stem cells, hematopoietic progenitor cells, B cells, T cells, NK cells, NKT cells, monocytes, macrophages, dendritic cells, neutrophils, and platelets. The expression of SLAMF receptors was studied during normal B cell maturation. Several SLAMF receptors were also detected in cancer cell lines of B-lymphoid origin and in pathological B cells from patients with B cell chronic lymphoproliferative disorders (B-CLPD), the most frequent hematological malignancies in adults. This review summarizes current knowledge on the expression of SLAMF receptors and their adaptor proteins SAP and EAT-2 in B-CLPD. Several SLAMF receptors could be regarded as potential diagnostic and differential diagnostic markers, prognostic factors, and targets for the development of novel drugs for patients with B-CLPD.

Ageing-Related Neurodegeneration and Cognitive Decline.

Neuropathological assessment was conducted on 1630 subjects, representing 5% of all the deceased that had been sent to the morgue of Uppsala University Hospital during a 15-year-long period. Among the 1630 subjects, 1610 were ≥41 years of age (range 41 to 102 years). Overall, hyperphosphorylated (HP) τ was observed in the brains of 98% of the 1610 subjects, and amyloid ß-protein (Aß) in the brains of 64%. The most common alteration observed was Alzheimer disease neuropathologic change (ADNC) (56%), followed by primary age-related tauopathy (PART) in 26% of the subjects. In 16% of the subjects, HPτ was limited to the locus coeruleus. In 14 subjects (<1%), no altered proteins were observed. In 3 subjects, only Aß was observed, and in 17, HPτ was observed in a distribution other than that seen in ADNC/PART. The transactive DNA-binding protein 43 (TDP43) associated with limbic-predominant age-related TDP encephalopathy (LATE) was observed in 565 (35%) subjects and α-synuclein (αS) pathology, i.e., Lewy body disease (LBD) or multi system atrophy (MSA) was observed in the brains of 21% of the subjects. A total of 39% of subjects with ADNC, 59% of subjects with PART, and 81% of subjects with HPτ limited to the locus coeruleus lacked concomitant pathologies, i.e., LATE-NC or LBD-NC. Of the 293 (18% of the 1610 subjects) subjects with dementia, 81% exhibited a high or intermediate level of ADNC. In 84% of all individuals with dementia, various degrees of concomitant alterations were observed; i.e., MIXED-NC was a common cause of dementia. A high or intermediate level of PART was observed in 10 subjects with dementia (3%), i.e., tangle-predominant dementia. No subjects exhibited only vascular NC (VNC), but in 17 subjects, severe VNC might have contributed to cognitive decline. Age-related tau astrogliopathy (ARTAG) was observed in 37% of the 1610 subjects and in 53% of those with dementia.

Predictors of severe hepatotoxicity among retroviral infected adults on HAART regimen in Ilubabor Zone, Southwest Ethiopia.

Nearly half of the deaths among hospitalized human immuno deficiency virus-infected patients in the highly active antiretroviral therapy era have been attributed to liver disease. This may range from an asymptomatic mild increase of liver enzymes to cirrhosis and liver failure. Different works of literature elucidated both retroviral infection and the adverse effects of highly active antiretroviral therapy as a cause of hepatotoxicity. Individual adaptations to medications and environmental exposures, shaped by cultural norms and genetic predispositions, could potentially modulate the risk and progression of liver disease in this population. Therefore, this study aims to assess the predictors of severe hepatotoxicity in retroviral-infected adults receiving highly active antiretroviral therapy regimens within the Ilubabor Zone, Southwest Ethiopia. A facility-based cross-sectional study was conducted among adult retroviral-infected patients in five selected anti-retro virus therapy clinics from May1 to July 30/2022. A systematic sampling technique was used to select 457 study participants and Binary logistic regression statistical data analysis was used, P value < 0.05 was considered statistically significant. The prevalence of severe hepatotoxicity was 21.44% in the study population. CD+4 count < 200 cells/mm3 (AOR = 2.19, 95% CI 1.04-5.22, P = 0.01), human immunodeficiency virus co-infection with tuberculosis (AOR = 2.82, 95% CI 1.01-8.29, P = 0.03) and human immuno deficiency virus co-infection with hepatitis-B/hepatitis C virus (AOR = 5.02, 95% CI 1.82-16.41) were predictors of severe hepatotoxicity. The magnitude of severe hepatotoxicity was high among adult retroviral-infected patients on highly active anti-retroviral drug regimens. Co-infection of human immuno deficiency virus with hepatitis B virus or hepatitis C virus, tuberculosis and CD4+T-cell count below 200 cells/mm3 were predictors of severe hepatotoxicity. Therefore, HIV patients on highly active antiretroviral therapy require close attention and regular monitoring of their liver function.

The effect of ascending- descending ultrafiltration and sodium profiles on blood pressure in hemodialysis patients: a randomized cross-over study.

BACKGROUND: Considering no previous research into the utilization of ascending/descending ultrafiltration and linear sodium profiles in improving blood pressure among hemodialysis patients, the present study aimed to explore the effect of the A/D-UF along with linear sodium profiles on HD patients with hypotension. METHODS: Applying a crossover design, this clinical trial was fulfilled between December 2022 and June 2023 on 20 patients undergoing HD, randomized into two groups, each one receiving two intervention protocols, viz., (a) an intervention protocol in which the liquid sodium in the dialysis solution was linear and the UF profiling was A/D, and (b) a routine protocol or HD, wherein both liquid sodium and UF in the dialysis solution remained constant. The HD patients' BP was then checked and recorded at six intervals, namely, before HD, one, two, three, and four hours after it, and following its completion, within each session. The data were further statistically analyzed using the IBM SPSS Statistics 20 and the related tests. RESULTS: In total, 20 patients, including 12 men (60%) and 8 women (40%), with the mean age of 58.00 ± 14.54 on HD for an average of 54 months, were recruited in this study. No statistically significant difference was observed in the mean systolic and diastolic BP levels in the group receiving the A/D-UF profile all through the desired hours (p > 0.05), indicating that the patients did not face many changes in these two numbers during HD. Our cross-over clinical trial demonstrated a statistically significant reduction in symptomatic IDH episodes from 55 to 15% with the application of the A/D-UF profile (p < 0.05). CONCLUSION: The study demonstrated that the A/D-UF profile could contribute to the stability of blood pressure levels among HD patients, with no significant fluctuations observed during treatment sessions. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (no. IRCT20180429039463N5) on 07/01/2023.

HIV viral suppression and risk of viral rebound in patients on antiretroviral therapy: a two- year retrospective cohort study in Northern Tanzania.

BACKGROUND: The world is moving towards the third target of the Joint United Nations Programme on HIV/AIDS to ensure most people receiving antiretroviral therapy (ART) are virologically suppressed. Little is known about viral suppression at an undetectable level and the risk of viral rebound phenomenon in sub-Saharan Africa which covers 67% of the global HIV burden.This study aimed to investigate the proportion of viral suppression at an undetectable level and the risk of viral rebound among people living with HIV receiving ART in northern Tanzania. METHODOLOGY: A hospital based-retrospective study recruited people living with HIV who were on ART for at least two years at Kibong'oto Infectious Disease Hospital and Mawenzi Regional Referral Hospital in Kilimanjaro Region, Tanzania. Participants' two-year plasma HIV were captured at months 6, 12, and 24 of ART. Undetectable viral load was defined by plasma HIV of viral load (VL) less than 20copies/ml and viral rebound (VR) was considered to anyone having VL of more than 50 copies/ml after having history of undetectable level of the VL less than 20copies/ml. A multivariable log-binomial generalized linear model was used to determine factors for undetectable VL and viral VR. RESULTS: Among 416 PLHIV recruited, 226 (54.3%) were female. The mean (standard deviation) age was 43.7 (13.3) years. The overall proportion of undetectable VL was 68% (95% CI: 63.3-72.3) and 40.0% had viral rebound (95% CI: 34.7-45.6). Participants who had at least 3 clinic visits were 1.3 times more likely to have undetectable VL compared to those who had 1 to 2 clinic visits in a year (p = 0.029). Similarly, participants with many clinical visits ( > = 3 visits) per year were less likely to have VR compared to those with fewer visits ( = 2 visits) [adjusted relative risk (aRR) = 0.64; 95% CI: 0.44-0.93]. CONCLUSION: Participants who had fewer clinic visits per year(ART refills) were less likely to achieve viral suppression and more likely to experience viral rebound. Enhanced health education and close follow-up of PLHIV on antiretroviral therapy are crucial to reinforce adherence and maintain an undetectable viral load.

The sedentary behavior reduction in pregnancy intervention (SPRING) pilot and feasibility randomized trial.

Pregnant individuals rarely achieve moderate-to-vigorous intensity physical activity recommendations.Purpose The sedentary behavior reduction in pregnancy intervention (SPRING) pilot and feasibility randomized trial aimed to demonstrate feasibility, acceptability, and initial efficacy of a lower intensity intervention targeting reduced sedentary behavior and increased standing and steps.Methods First trimester pregnant individuals at risk for high sedentary behavior and adverse pregnancy outcomes (APO) were randomized 2:1 to a multi-component sedentary behavior reduction intervention or no-contact control. Intervention components included biweekly remote health coaching, wearable activity monitor, height-adjustable workstation, and a private Facebook group. Evidence-based behavioral targets included sedentary time < 9 h/day, increasing standing by 2-3 h/day, and ≥ 7500 steps/day. Participants completed all-remote assessments (baseline, second trimester, third trimester) of sedentary behavior and activity (thigh-worn activPAL) along with exploratory pregnancy health outcomes abstracted from medical records. Intervention effects vs. control were evaluated using generalized mixed models and an intention-to-treat approach. Intervention participants also provided feedback on perceived benefits and acceptability.Results Participants (34 intervention; 17 control) had mean age 32 years, were 83% White, with mean pre-pregnancy BMI 28 kg/m2. Retention was high (90% and 83% at second and third trimester follow-up visits). Intervention participants decreased sedentary time (-0.84 h/day, p = 0.019) and increased standing (+0.77 h/day, p = 0.003), but did not increase steps/day (+710, p = 0.257) compared to controls. Intervention participants reported many perceived benefits and identified the wearable, height-adjustable workstation, and behavioral lessons as most useful.Conclusion For pregnant individuals at risk for high sedentary behavior and APOs, a sedentary behavior reduction intervention is feasible, acceptable, and may offer a viable alternative to more intense physical activity recommendations during pregnancy. Further testing in a fully powered clinical trial is warranted.Trial registration NCT05093842 on clinicaltrials.gov.

Empowering patients in primary care: a qualitative exploration of the usability and utility of an online diabetes self-management tool.

BACKGROUND: Despite the potential advantages of Internet-based diabetes self-management education, its adoption was not widespread among Singapore's public primary care clinics (polyclinics). An interactive online tool was thus developed to help educate patients with Type 2 diabetes mellitus (T2DM), and was now ready for user testing before implementation. AIM: To explore the perceived utility and usability of the educational tool in patients with suboptimally-controlled T2DM in a Singapore primary care setting. METHODS: In-depth interviews were used to gather qualitative data from multi-ethnic Asian adults who had suboptimally-controlled T2DM. A total of 17 IDIs were conducted between April 2022 to March 2023, audio-recorded, transcribed, and analyzed to identify emergent themes via thematic analysis. RESULTS: Regarding utility, users found the educational tool useful because it provided them with information that was comprehensive, accessible, reliable, and manageable. Regarding usability, the majority of users reported that the educational tool was easy to use, and suggested ways to improve navigational cues, visual clarity, readability and user engagement. CONCLUSION: Participants generally found the educational tool useful and easy to use. A revised educational tool will be developed based on their feedback and implemented in clinical practice.

Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases.

Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene. Central nervous system tumors, such as choroid plexus tumors, medulloblastomas, and diffuse gliomas, are frequently found in patients with LFS. Although molecular profiles of diffuse gliomas that develop in pediatric patients with LFS have been elucidated, those in adults are limited. Recently, diffuse gliomas have been divided into pediatric- and adult-type gliomas, based on their distinct molecular profiles. In the present study, we investigated the molecular profiles of high-grade gliomas in three adults with LFS. These tumors revealed characteristic histopathological findings of high-grade glioma or glioblastoma and harbored wild-type IDH1/2 according to whole exome sequencing (WES). However, these tumors did not exhibit the key molecular alterations of glioblastoma, IDH-wildtype such as TERT promoter mutation, EGFR amplification, or chromosome 7 gain and 10 loss. Although WES revealed no other characteristic gene mutations or copy number alterations in high-grade gliomas, such as those in histone H3 genes, PDGFRA amplification was found in all three cases together with uniparental disomy of chromosome 17p, where the TP53 gene is located. DNA methylation analyses revealed that all tumors exhibited DNA methylation profiles similar to those of pediatric-type high-grade glioma H3-wildtype and IDH-wildtype (pHGG H3-/IDH-wt), RTK1 subtype. These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.

Patient-reported experience with Fabry disease and its management in the real-world setting: results from a double-blind, cross-sectional survey of 280 respondents.

BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with a heterogeneous clinical presentation. Patients with FD may exhibit early signs/symptoms including neuropathic pain, gastrointestinal complaints, and dermatologic manifestations. FD may ultimately progress to renal, neurologic, and cardiac dysfunction. Current treatments for FD have significantly improved the management and outcomes for patients with FD, but important clinical and convenience limitations still exist. METHODS: To illuminate the impact of FD on daily life from the patient's perspective, we asked adult patients (≥ 18 years old) with FD in the United States and Canada to complete a 33-question online survey to assess patient-reported disease severity, management, and treatment outcomes. RESULTS: A total of 280 respondents with FD completed the survey; they had a mean age of 47 years, and 68% (191/280) were women. Most were currently receiving FD treatment (84%, 234/280) with enzyme replacement therapy (ERT) (89%, 208/234) or chaperone therapy (11%, 26/234). Common symptoms included low energy/fatigue (72%, 201/280), tingling (62%, 174/280) or pain in the hands/feet (60%, 168/280), ringing in ears/hearing loss (54%, 151/280), general body pains/pain crises (51%, 143/280), and abdominal/stomach pain (50%, 140/280). More than half (51%, 144/280) of respondents reported their symptoms as bothersome (38%, 106/280) or difficult to control (14%, 38/280). Temporary symptom worsening between infusions was reported by about half of respondents: 51% (108/211) currently receiving ERT and 48% (14/29) previously receiving ERT. Only 48% (59/122) of respondents reported their symptom worsening to their physician. Of those who reported it, 41% (24/59) said that their physician prescribed medication to manage their symptoms or changed their treatment regimen. CONCLUSIONS: Our analysis highlights the gap between current standard-of-care in disease monitoring and patient perception of disease progression among patients with FD. This information may be helpful for healthcare providers and drug developers seeking to improve the care of patients with FD by addressing unmet needs of high relevance.

Predicting COVID-19 outcomes with the Edmonton Obesity Staging System.

BACKGROUND: Multiple studies have demonstrated a correlation between a high body mass index and discriminatory COVID-19 outcomes. Studies appear to indicate that there is a correlation between obesity-related comorbidities and less favorable outcomes. OBJECTIVES: The primary aim of the current investigation is to conduct a thorough assessment of the correlation between BMI and comorbidities associated with obesity, and their potential impact on the severity and consequences of COVID-19 infection among patients receiving care in a tertiary healthcare setting. DESIGN: Retrospective cohort. SETTINGS: Tertiary rehabilitation center, Riyadh, Saudi Arabia. PATIENTS AND METHODS: The study included all individuals who received medical treatment and tested positive for COVID-19 by means of RT-PCR during the period from March to September 2020. COVID-19 patients were classified using Edmonton Obesity Staging System (EOSS). MAIN OUTCOME MEASURES: COVID-19-related complications, including pneumonia and cytokine release syndrome, as well as the time length to COVID-19 negativization. SAMPLE SIZE: 315 patients. RESULTS: The median (25th-75th percentiles) age of the patients was 38 (31.5-49) years old. Males outnumbered females, and 66% of patients were non-Saudis. Forty-eight patients (15.2%) had obesity class I, whereas 13 patients (4.1%) had class II. Thirty-two patients (10.2%) were classified as EOSS stage 1, 105 patients (33.3%) were classified as EOSS stage 2, and 25 patients (7.9%) were assigned to EOSS stage 3. Males predominated in EOSS stages 1 and 2, whereas females predominated in stage 3. In EOSS stage 3, 52% of cases had moderate severity and 48% had severe illness. CONCLUSIONS: EOSS distinguishes the COVID-19 risks of poor outcomes beyond BMI. Patients who were overweight or obese but remained in the stage 1 of the EOSS had a lower risk of a poor COVID-19 outome than normal-weight patients. The health status of obese patients is a more precise indicator of the progression of COVID-19 during hospitalization than BMI alone. LIMITATIONS: Given the limited capacity of urgent care facilities to conduct a comprehensive evaluation of comorbidities and other relevant outcomes in all patients, it is plausible that certain patients may have been erroneously classified with an EOSS stage 2 diagnosis, when in fact they ought to have been assigned a stage 3 diagnosis.

Fuchs' uveitis syndrome: a 20-year experience in 466 patients.

Fuchs Uveitis Syndrome (FUS), also known as Fuchs Heterochromic Iridocyclitis, is a chronic form of uveitis characterized by mild inflammation primarily affecting one eye. This study aimed to investigate the clinical and epidemiological features of FUS in an Iranian population. A retrospective analysis was conducted on 466 patients diagnosed with FUS at an ophthalmology center affiliated with Isfahan University of Medical Sciences between 2003 and 2021. The Kimura et al. criteria were used for FUS diagnosis. Demographic data, clinical characteristics, misdiagnosed cases, concurrent diseases, and associated ocular findings were analyzed. The study included 507 eyes of 466 FUS patients, with a mean age of 34.01 ± 11.25 years. Iris atrophy, keratic precipitates, and vitritis were common clinical findings. Heterochromia was an infrequent feature. Initial misdiagnosis occurred in 13 patients, with pars planitis being the most common incorrect diagnosis. Toxoplasmosis and multiple sclerosis were common concurrent diseases. Pediatric FUS cases were noted, possibly attributed to early-onset manifestations. Differences in clinical characteristics were observed when compared to other populations. This study provides insights into the clinical and epidemiological aspects of FUS in an Iranian population. Variations in clinical features, misdiagnosis patterns, and concurrent diseases were noted. Attention to specific clinical parameters can aid in accurate FUS diagnosis. Understanding these differences contributes to a better understanding of FUS presentation and its relationship with other diseases.

Corneal endothelial cell density and associated factors among adults at a regional referral hospital in Uganda: a cross-sectional study.

BACKGROUND: To assess the prevalence of low corneal endothelial cell density and correlates of corneal endothelial cell density among adults attending Mbarara University and Referral Hospital Eye Centre in Uganda. METHODS: In this hospital-based cross-sectional study, participants 18 years and older, were enrolled. We obtained informed consent, and basic demographic data. We also conducted visual acuity, a detailed slit lamp examination, intra-ocular pressure, corneal diameter, tear-film break-up time, keratometry, A-scan, and pachymetry on all participants. A confocal microscope Heidelberg HRT3 was used to examine the central cornea and to obtain the mean cell density (cells/mm2). To calculate the proportion of low endothelial cell density, descriptive statistics were used, whereas correlates of endothelial cell density were assessed, using linear regression analyses. RESULTS: We evaluated a total of 798 eyes of 404 participants aged between 18 and 90 years (males = 187, females = 217). The average endothelial cell density was 2763.6 cells/mm2, and there was a decrease in endothelial cell density with increasing age, irrespective of gender. There was no significant difference in endothelial cell density between males and females. Increasing age (adjusted coefficient - 10.1, p < 0.001), history of smoking (adjusted coefficient - 439.6, p = 0.004), history of ocular surgery (adjusted coefficient - 168.0, p = 0.023), having dry eye (adjusted coefficient - 136.0, p = 0.051), and having arcus senilis (adjusted coefficient - 132.0, p = 0.08), were correlated with lower endothelial cell density. However, increasing corneal diameter (adjusted coefficient 134.0, p = 0.006), increasing central corneal thickness (adjusted coefficient 1.2, p = 0.058), and increasing axial length (adjusted coefficient 65.8, p = 0.026), were correlated with higher endothelial cell density. We found five eyes (0.63%) from different participants with a low endothelial cell density (< 1000cells/mm2). CONCLUSION: Our study established baseline normal ranges of ECD in a predominantly black African population, and found that low ECD is rare in our population. The elderly, smokers, and those with past ocular surgery are the most vulnerable. The low prevalence could be due to a lack of reference values for the black African population.

Multi-organ involvement caused by Scedosporium apiospermum infection after near drowning: a case report and literature review.

BACKGROUND: Scedosporium apiospermum (S. apiospermum) is a rare fungal pathogen that causes disseminated infections. It rarely affects immunocompetent individuals and has a poor prognosis. CASE PRESENTATION: A 37-year-old woman presented with multiple lesions in the lungs, brain, and eyes, shortly after near drowning in a car accident. The primary symptoms were chest tightness, limb weakness, headache, and poor vision in the left eye. S. apiospermum infection was confirmed by metagenomic next-generation sequencing (mNGS) of intracranial abscess drainage fluid, although intracranial metastases were initially considered. After systemic treatment with voriconazole, her symptoms improved significantly; however, she lost vision in her left eye due to delayed diagnosis. CONCLUSION: While S. apiospermum infection is rare, it should be considered even in immunocompetent patients. Prompt diagnosis and treatment are essential. Voriconazole may be an effective treatment option.

Smoking on the risk of acute respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: The relationship between smoking and the risk of acute respiratory distress syndrome (ARDS) has been recognized, but the conclusions have been inconsistent. This systematic review and meta-analysis investigated the association between smoking and ARDS risk in adults. METHODS: The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies published from January 1, 2000, to December 31, 2023. We enrolled adult patients exhibiting clinical risk factors for ARDS and smoking condition. Outcomes were quantified using odds ratios (ORs) for binary variables and mean differences (MDs) for continuous variables, with a standard 95% confidence interval (CI). RESULTS: A total of 26 observational studies involving 36,995 patients were included. The meta-analysis revealed a significant association between smoking and an increased risk of ARDS (OR 1.67; 95% CI 1.33-2.08; P < 0.001). Further analysis revealed that the associations between patient-reported smoking history and ARDS occurrence were generally similar to the results of all the studies (OR 1.78; 95% CI 1.38-2.28; P < 0.001). In contrast, patients identified through the detection of tobacco metabolites (cotinine, a metabolite of nicotine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of tobacco products) showed no significant difference in ARDS risk (OR 1.19; 95% CI 0.69-2.05; P = 0.53). The smoking group was younger than the control group (MD - 7.15; 95% CI - 11.58 to - 2.72; P = 0.002). Subgroup analysis revealed that smoking notably elevated the incidence of ARDS with extrapulmonary etiologies (OR 1.85; 95% CI 1.43-2.38; P < 0.001). Publication bias did not affect the integrity of our conclusions. Sensitivity analysis further reinforced the reliability of our aggregated outcomes. CONCLUSIONS: There is a strong association between smoking and elevated ARDS risk. This emphasizes the need for thorough assessment of patients' smoking status, urging healthcare providers to vigilantly monitor individuals with a history of smoking, especially those with additional extrapulmonary risk factors for ARDS.