Russian Mathematical Surveys最新文献

Context/objectives: Cardiometabolic disease (CMD) is increased after spinal cord injury (SCI), with an increased number of CMD risk factors that relate to higher mortality. The study objective was to characterize the relationship of age and injury duration with CMD.

Design: Retrospective cohort assessment of CMD risks using unbiased recursive partitioning to divide for group comparison: (1) Lowest Risk, (2) Moderate Risk, and (3) Highest Risk based on classification and regression trees predicting CMD diagnosis by age and injury duration.

Setting: Academic rehabilitation center laboratory.

Participants: Adults (N = 103; aged 18-75) with traumatic SCI (C4-L2) of 3 months to 42 years duration.

Interventions: NA.

Outcome measures: CMD risk factors (obesity, insulin resistance, dyslipidemia, and hypertension) using Paralyzed Veterans of America SCI-specific guidelines.

Results: Obesity was prevalent (82%) and co-occurred with most other risk factors present. Age increased odds for CMD diagnosis by 1.05 per year (P = 0.02) and was directly related to elevated body mass index (BMI, β = 0.42, P < 0.05), fasting glucose (β =  0.58, P < 0.01), and higher systolic blood pressure (β = 0.31, P < 0.10). In contrast, time since injury contributed to lower risk factor count (β = -0.29, P < 0.10) and higher HDL-C (β = 0.50, P < 0.01), and was not related to odds of CMD diagnosis.

Conclusion: While SCI is linked to an increased risk of CMD, age is associated with higher CMD risk. Increased SCI duration related to improvement in individual CMD risk factors but did not decrease overall risk for CMD diagnosis. SCI may not uniformly increase CMD risks and highlight a necessary focus on weight management for risk prevention.

Despite the National Occupational Safety and Legislation Act 2020's implementation, reports of workplace accidents are rising in India. Various ear, nose, and throat conditions have been linked to a wide range of physico-chemical variables. Due to a lack of training, inadequate knowledge, a lack of awareness of occupational health and safety risks, or a lack of accessibility to or use of personal protective equipment (PPE), sculptors are frequently exposed to a variety of physical, compound and unplanned risks, chemical, and accidental hazards. The study aimed to assess the various ear, nose and throat manifestations like noise induced hearing loss, occupational rhinitis and non-infectious pharyngitis among the sculptors working in the southern part of Chennai. This observational study was performed in a total of 110 sculptors. Demographic data like age, education, duration of occupation, use of PPE like face mask, ear plug during work hours, whether sculpting is a family occupation or first generation sculptor. A detailed history and thorough ENT examination was performed with pure tone audiometry (PTA), diagnostic nasal endoscopy (DNE) and videolaryngoscopy (VLS). If any problem is detected they will be treated accordingly. Most of them (70%) were in the age group of 21-40 years but 71% of them are sculptors for more than 15 years which infers introduction to the occupation at an early age. The reason for this could be more than 80% of them possessed the heritage of sculpting as their family occupation. Duration of occupation was significantly associated with chronic rhinitis (P value was 0.002) and NIHL (P value was 0.002) whereas education and use of PPE like face mask or ear plugs were not associated with ENT manifestations. This study focuses on the sculptors' working habits, their ignorance of safety precautions, and an assessment of the numerous ENT ailments. These manifestations showed a strong correlation to exposure time. To prevent the issues from becoming more severe, regular medical monitoring is required for early detection and intervention.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has made it clear that further development of antiviral therapies will be needed to combat additional SARS-CoV-2 variants or novel CoVs. Here, we describe small molecule inhibitors for SARS-CoV-2 Mac1, which counters ADP-ribosylation mediated innate immune responses. The compounds inhibiting Mac1 were discovered through high-throughput screening (HTS) using a protein FRET-based competition assay and the best hit compound had an IC₅₀ of 14 μM. Three validated HTS hits have the same 2-amide-3-methylester thiophene scaffold and the scaffold was selected for structure-activity relationship (SAR) studies through commercial and synthesized analogs. We studied the compound binding mode in detail using X-ray crystallography and this allowed us to focus on specific features of the compound and design analogs. Compound 27 (MDOLL-0229) had an IC₅₀ of 2.1 μM and was generally selective for CoV Mac1 proteins after profiling for activity against a panel of viral and human ADP-ribose binding proteins. The improved potency allowed testing of its effect on virus replication and indeed, 27 inhibited replication of both MHVa prototype CoV, and SARS-CoV-2. Furthermore, sequencing of a drug-resistant MHV identified mutations in Mac1, further demonstrating the specificity of 27. Compound 27 is the first Mac1 targeted small molecule demonstrated to inhibit coronavirus replication in a cell model. This, together with its well-defined binding mode, makes 27 a good candidate for further hit/lead-optimization efforts.