Effective and sustainable collaborative evidence networks have innovative ways of relating and mobilizing energy for action and combine formal and informal structures and relationships to successfully work together to address complex global health issues and drive the EBHC agenda forward.
Although veterans represent a significant proportion (7%) of the USA population, the COVID-19 disease impact within this group has been underreported. To bridge this gap, this study was undertaken.
A total of 419,559 veterans, who tested positive for COVID-19 disease in the Veterans Affairs hospital system from March 1st, 2020 to December 31st, 2021 with 60-days follow-up, was included in this retrospective review. Primary outcome measures included age-adjusted incidences and relative incidences of COVID-19 hospitalization, mechanical ventilation, and case-fatality outcomes.
Of this veteran cohort with COVID-19 disease, predominately 85.7% were male, 59.1% were White veterans, 27.5% were ages 50-64, and 40.5% were obese. Although Black veterans were at 63% higher relative risk (RR) for hospitalization incidences, they had a similar risk RR for in-hospital deaths compared to the White-veteran referent. Asian, American Indian/Alaska Native races, advanced age ≥65, and the underweight were at high RR for mechanical ventilator and/or in-hospital deaths compared to respective referent groups. Veterans who are ≥85 years old had a nearly 5-fold higher incidence of death compared respective referent group. The monthly outcomes for hospitalization, ventilation, and case-fatality data showed decreasing trends with time.
An increased incidence of death was associated with age ≥65 years and underweight veterans compared to the referent group. Age-adjusted data, however, did not show any increased incidence of death in Black veterans compared to White veterans.
3 (Case-control studies; retrospective cohort study).
3 (Case-control studies; retrospective cohort study).
The incidence of Endometrial cancer (EC) has grown substantially in Asia over the past decade. However, few studies have addressed risk factors associated with EC incidence in Asian populations. We explored the association between reproductive and dietary risk factors and EC in the Singapore Chinese Health Study (SCHS), one of the largest prospective cohort studies in Asia.
Data were collected from 34,028 ethnically Chinese women aged 45-74 residing in Singapore, enrolled between 1993 and 1998. Baseline demographic, dietary, and reproductive factors were collected via structured questionnaires. EC cases were identified from the Singapore Cancer Registry (n=126) up to 2010. Cox proportional hazard models were used to analyze association between EC and personal, reproductive, and dietary factors.
The incidence of EC in this population was 28.8 per 100,000 person-years. Regardless of menopausal status, obesity (BMI ≥ 27) was associated with increased EC risk (HR=2.22, 95% CI 1.26-3.92), while later age at similarities.Transcriptional coactivators play a crucial role in regulating gene expression. PRIP interacting protein with methyl transferase domain (PIMT)/trimethyl guanosine synthase 1 (TGS1) is a co-activator interacting protein with an RNA methyl transferase domain. PIMT serves as a bridge between HAT and non-HAT coactivators and differentially modulates gene expression. Disruption of PIMT is embryonic lethal. PIMT regulates hepatic gluconeogenesis and TNF-α-induced insulin resistance in the skeletal muscle. As a methyl transferase, PIMT controls post-transcriptional regulation of HIV-1 and is essential for human telomerase RNA biogenesis. This review comprehensively describes the dual role of PIMT, which promises to be a putative target in metabolic disorders.The inefficient tumor penetration of therapeutic antibodies has hampered their effective use in treating solid tumors. Here, we report the identification of a fully human single-domain antibody (UdAb), designated as n501, targeting the oncofetal antigen 5T4. The high-resolution crystal structure indicates that n501 adopts a compact structure very similar to that of camelid nanobodies, and binds tightly to all eight leucine-rich repeats of 5T4. Furthermore, the UdAb n501 exhibits exceptionally high stability, with no apparent activity changes over 4 weeks of storage at various temperatures. Importantly, the UdAb-based antibody-drug conjugate (n501-SN38) showed much deeper tumor penetration, significantly higher tumor uptake, and faster accumulation at tumor sites than conventional IgG1-based antibody-drug conjugate (m603-SN38), resulting in improved tumor inhibition. These results highlight the potential of UdAb-based antibody-drug conjugates as a potential class of antitumor therapeutics with characteristics of high stability and strong tumor penetration for the effective treatment of solid tumors.
Individuals with SARS-CoV-2 infection and (pre-existing) diabetes, including pregnant women, present with more severe morbidity, as compared to non-diabetic subjects. To date, evidence is limited concerning the role of gestational diabetes (GDM) in severity of SARS-CoV-2 infection during pregnancy, or vice versa. The aim of our study was to investigate the prevalence of GDM in a SARS-CoV-2 infected pregnant population and evaluate risk factors for and from severe infection in these patients.
A case-control study with prospective data collection for the case group and 12 matching with historical controls based on parity, BMI and ethnicity was conducted (n=224). GDM screening was performed at 26 weeks' gestation. Multivariate binary logistic regression analysis was performed to assess risk factors for GDM and inpatient COVID-19 management.
34.6% of the patients in the case group suffered from GDM, vs. 16.1% in the control group (p=0.002). 35.7% patients were diagnosed with GDM after, vs. 33.3% before SARS-CoV-2 infection (OR (95%CI) 1.11(0.40-3.08), p=0.84), with no correlation between time point of infection and GDM diagnosis. SARS-CoV-2 (OR (95%CI) 2.79 (1.42, 5.47), p=0.003) and BMI (OR (95%CI) 1.12 (1.05, 1.19), p=0.001) were significant independent risk factors for GDM.
Data suggests that GDM increases the risk of infection in SARS-CoV-2 infected pregnant women. Meanwhile, SARS-CoV-2 during pregnancy might increase the risk of developing GDM. Vaccination and caution in using protective measures should be recommended to pregnant women, particularly when suffering from GDM.
Data suggests that GDM increases the risk of infection in SARS-CoV-2 infected pregnant women. Meanwhile, SARS-CoV-2 during pregnancy might increase the risk of developing GDM. Vaccination and caution in using protective measures should be recommended to pregnant women, particularly when suffering from GDM.
We assessed vaccination-induced antibody and cellular responses against spike from the ancestral strain and from the delta (δ) SARS-CoV-2 variant in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy in comparison with immunocompetent subjects.
We enrolled patients with IMID and immunocompetent subjects who completed the vaccination schedule within 4-6 months from the first dose. The interferon (IFN)-γ-response to spike peptides that were derived from the ancestral and the δ SARS-CoV-2 were measured by ELISA. Anti-Receptor Binding Domain IgG antibodies were also evaluated.
We enrolled 43 patients with IMID and nine immunocompetent subjects. No significant differences were found after comparing the specific immune response (IFN-γ) between patients with IMID and immunocompetent subjects to the ancestral (p=0.36) or δ peptide pool (p=0.51). Nevertheless, IFN-γ-specific responses to the ancestral or to the δ pools were reduced in subjects taking CTLA4-IgG or TNF-α inhibitors compared with subjects treated with IL-6 inhibitors or Disease Modifying Anti-Rheumatic Drugs. Regarding the antibody response, no significant differences were observed between patients with IMID and immunocompetent individuals.
Cellular responses to δ SARS-CoV-2 variant remain largely intact in patients with IMID. However, the magnitude of these responses is dependent on the specific IMID immunosuppressive regimen. Serological response was also similar between the IMID and control groups.
Cellular responses to δ SARS-CoV-2 variant remain largely intact in patients with IMID. However, the magnitude of these responses is dependent on the specific IMID immunosuppressive regimen. Serological response was also similar between the IMID and control groups.
The SARS-CoV-2 Omicron (B.1.1.529) variant has caused global concern. Previous studies have shown that the variant has enhanced immune evasion ability and transmissibility and reduced severity.
In this study, we developed a mathematical model with time-varying transmission rate, vaccination, and immune evasion. We fit the model to reported case and death data up to February 6, 2022 to estimate the transmissibility and infection fatality ratio of the Omicron variant in South Africa.
We found that the high relative transmissibility of the Omicron variant was mainly due to its immune evasion ability, whereas its infection fatality rate substantially decreased by approximately 78.7% (95% confidence interval 66.9%, 85.0%) with respect to previous variants.
On the basis of data from South Africa and mathematical modeling, we found that the Omicron variant is highly transmissible but with significantly lower infection fatality rates than those of previous variants of SARS-CoV-2.
On the basis of data from South Africa and mathematical modeling, we found that the Omicron variant is highly transmissible but with significantly lower infection fatality rates than those of previous variants of SARS-CoV-2.Recovery from COVID-19 is not always uneventful, especially in critically ill hospitalized patients. Persistent symptoms including fatigue/ weakness, shortness of breath, anxiety, and depression have been described at one-year follow-up. Furthermore, symptoms from the musculoskeletal system like joint pain or stiffness are underreported in studies with long-term follow-up of up to one year. Infection with SARS-CoV-2 itself has been associated with endothelial damage, and together with high-dose corticosteroid treatment, it is predisposed to the dissemination of microthrombi and the development of femoral head osteonecrosis (FHOn), as it has been shown during the previous (2003-2004) coronavirus outbreaks. A resurgence of FHOn cases is anticipated but this is not reflected in the existing studies with long-term follow-up. Prompt diagnosis is critical for early treatment and possibly for the hip joint preservation. Patients with COVID-19 treated with corticosteroids should be screened for avascular necrosis early after discharge from the hospital. Every healthcare worker involved in the management of these patients should maintain a high level of suspicion and should be alert when patients report symptoms such as vague aches at the buttocks, hip area, adductors, and/or above the knee. https://www.selleckchem.com/products/fin56.html Studies are needed to identify risk factors for FHOn including disease severity, type of steroid, cumulative dose, and duration of treatment.