Nevin Manimala

J Recept Signal Transduct Res. 2022 Mar 9:1-9. doi: 10.1080/10799893.2022.2044860. Online ahead of print.

ABSTRACT

Mycobacterium tuberculosis (Mtb) is the causative agent of infectious diseases worldwide. Oxadiazole derivatives have many biological activities and can be a good alternative to antimicrobial drugs. In this study, the quantitative structure-activity relationship (QSAR) of fifty-one novel oxadiazoles derivatives has been studied using the density functional theory (DFT) and statistical methods. Becke’s three-parameter hybrid method and the Lee-Yang-Parr B3LYP functional employing 6-31++G (d) basis set are used to calculated quantum chemical descriptors using Gaussian09 software. The other descriptors including Lipinski, physicochemistry, topological, etc. were calculated using Chembio3d software. Statistically, the best correlation between the independent variables and the PMIC as the dependent variable was a 6-variable equation for which the correlation coefficient were as follows R² = 0.86 and R = 0.93. Also, the values of MAE = 0.003 and Q²_CV = 0.9 confirm the acceptability of the obtained model. The obtained equation shows that NRB, energy gap (ΔE), Henry’s law constant, O-C, and C-N bonds length, and the Free Gibbs energy have the highest correlation with the anti-Tb activity.

PMID:35263550 | DOI:10.1080/10799893.2022.2044860

Environ Sci Technol. 2022 Mar 9. doi: 10.1021/acs.est.2c01177. Online ahead of print.

NO ABSTRACT

PMID:35263543 | DOI:10.1021/acs.est.2c01177

N Engl J Med. 2022 Mar 9. doi: 10.1056/NEJMoa2200797. Online ahead of print.

ABSTRACT

BACKGROUND: Waning of vaccine protection against coronavirus disease 2019 (Covid-19) and the emergence of the omicron (or B.1.1.529) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to expedited efforts to scale up booster vaccination. Protection conferred by booster doses of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar, as compared with protection conferred by the two-dose primary series, is unclear.

METHODS: We conducted two matched retrospective cohort studies to assess the effectiveness of booster vaccination, as compared with that of a two-dose primary series alone, against symptomatic SARS-CoV-2 infection and Covid-19-related hospitalization and death during a large wave of omicron infections from December 19, 2021, through January 26, 2022. The association of booster status with infection was estimated with the use of Cox proportional-hazards regression models.

RESULTS: In a population of 2,239,193 persons who had received at least two doses of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine, those who had also received a booster were matched with persons who had not received a booster. Among the BNT162b2-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 2.4% (95% confidence interval [CI], 2.3 to 2.5) in the booster cohort and 4.5% (95% CI, 4.3 to 4.6) in the nonbooster cohort after 35 days of follow-up. Booster effectiveness against symptomatic omicron infection, as compared with that of the primary series, was 49.4% (95% CI, 47.1 to 51.6). Booster effectiveness against Covid-19-related hospitalization and death due to omicron infection, as compared with the primary series, was 76.5% (95% CI, 55.9 to 87.5). BNT162b2 booster effectiveness against symptomatic infection with the delta (or B.1.617.2) variant, as compared with the primary series, was 86.1% (95% CI, 67.3 to 94.1). Among the mRNA-1273-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 1.0% (95% CI, 0.9 to 1.2) in the booster cohort and 1.9% (95% CI, 1.8 to 2.1) in the nonbooster cohort after 35 days; booster effectiveness against symptomatic omicron infection, as compared with the primary series, was 47.3% (95% CI, 40.7 to 53.3). Few severe Covid-19 cases were noted in the mRNA-1273-vaccinated cohorts.

CONCLUSIONS: The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19-related hospitalization and death. (Funded by Weill Cornell Medicine-Qatar and others.).

PMID:35263534 | DOI:10.1056/NEJMoa2200797

J Diabetes Investig. 2022 Mar 9. doi: 10.1111/jdi.13786. Online ahead of print.

ABSTRACT

To estimate the trends in the prevalence of severe hypoglycemia (SH) in patients with type 2 diabetes (T2D) in Korea, we investigated the total number of SH episodes among T2D patients aged ≥30 years who visited the emergency department between 2002 and 2019, using the Korean National Health Insurance Service database. The prevalence of SH events increased from 2002 to 2012; however, it has decreased gradually since 2012. In 2019, the prevalence of SH was 0.6%, with an incidence rate of 4.43 per 1,000 person-years. Approximately 23,000 SH events occur every year in Korea. Although the incidence is steadily decreasing, there are a considerable number of SH events in T2D patients. The decline in the incidence of SH seems to most likely be due to the increased prescription rate of hypoglycemic agents without hypoglycemia risk, less strict treatment goals, and the individualization of therapy.

PMID:35263509 | DOI:10.1111/jdi.13786

Vet Med Sci. 2022 Mar 8. doi: 10.1002/vms3.782. Online ahead of print.

ABSTRACT

BACKGROUND: Radiation therapy (RT) is used for local pain alleviation in dogs with appendicular osteosarcoma (OS), especially among dogs that are poor surgical candidates for amputation. However, many historical reports of fractionated protocols lack time to fracture and fracture rates.

OBJECTIVES: The primary objectives of this retrospective study were to determine fracture rate and time to fracture of dogs receiving RT (coarse or fine fractionated) for appendicular OS. Secondary objectives were to evaluate tolerability and disease outcome measures.

METHODS: Fifty-one dogs that received RT as part of treatment for appendicular OS were available for evaluation. Forty-five received coarse fractionation (C-RT, 8 or 6 Gy per fraction protocols [C-RT8 or C-RT6]) while the remaining six received fine fractionation (F-RT).

RESULTS: The overall pathologic fracture rate was 37%. Pathologic fracture rate was significantly higher for dogs that received F-RT (5/6, 83%) compared to dogs that received C-RT (12/40, 30%, p = 0.021). In the 17 dogs that fractured, the overall median time to fracture was 57 days. For all dogs, the median progression free interval (PFI) and median overall survival time (OST) were 90 and 140 days, respectively. In a very small cohort of dogs (n = 7) treated with zoledronate and RT, fracture rate was 0% and extended survival times were noted.

CONCLUSIONS: In conclusion, C-RT is recommended over F-RT due to lower risk of pathologic fracture and similar PFI. Prospective evaluation of combined C-RT and zoledronate, especially for dogs with poor surgical candidacy, is warranted for the treatment of canine appendicular osteosarcoma.

PMID:35263506 | DOI:10.1002/vms3.782

Pediatr Transplant. 2022 Mar 9:e14265. doi: 10.1111/petr.14265. Online ahead of print.

ABSTRACT

BACKGROUND: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients.

METHODS: This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26.

RESULTS: One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented.

CONCLUSION: This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated.

PMID:35263498 | DOI:10.1111/petr.14265

Eur J Pain. 2022 Mar 9. doi: 10.1002/ejp.1937. Online ahead of print.

ABSTRACT

BACKGROUND: The objective of this study was to develop prediction models and explore the external validity of the models in a large sample of patients with chronic widespread pain (CWP) and fibromyalgia (FM).

METHODS: Patients with CWP and FM referred to rehabilitation services in Norway (n=986) self-reported data on potential predictors prior to entering rehabilitation, and self-reported outcomes at one-year follow-up. Logistic regression models of improvement, worsening and work status, and a linear regression model of health-related quality of life (HRQoL), were developed using lasso regression. Externally validated estimates of model performance were obtained from the validation set.

RESULTS: The number of participants in the development and the validation sets was 771 and 215 respectively; only participants with outcome data (n = 519-532 and 185, respectively) were included in the analyses. On average, HRQoL and work status changed little over one year. The prediction models included 10-11 predictors. Discrimination (AUC statistic) for prediction of outcome at follow-up was 0.71 for improvement, 0.67 for worsening, and 0.87 for working. The median absolute error of predictions of HRQoL was 0.36 (0.22-0.51). Reasonably good predictions of working at follow-up and HRQoL could be obtained using only the baseline scores as predictors.

CONCLUSIONS: Moderately complex predictions models (10-11 predictors) generated poor to excellent predictions of patient-relevant outcomes. Simple prediction models of working and HRQoL at follow-up may be nearly as accurate and more practical.

PMID:35263480 | DOI:10.1002/ejp.1937

Andrologia. 2022 Mar 8:e14415. doi: 10.1111/and.14415. Online ahead of print.

ABSTRACT

The purpose of this study is to evaluate the impact of a microfluidic approach for spermatozoon selection in male infertility patients undergoing intracytoplasmic sperm injection (ICSI). This research enrolled 128 individuals who had ICSI for male-factor infertility. The patients were separated into two groups according to the method used to pick the spermatozoa: group I (n = 64), which used traditional swim-up procedures, and group II (n = 64), which used the Fertile Chip for spermatozoon selection during ICSI therapy. Fertilization rates and embryo quality were the major outcomes. The rates of pregnancy, clinical pregnancy and live birth were used as secondary outcomes. As a result, there was no statistically significant difference between the two groups in terms of fertilization rate, total grade 1 and 2 embryos. Implantation rate was significantly higher in the Fertile Chip group than in the control group (50% vs. 31%, p = 0.02). The Fertile Chip group had considerably greater pregnancy rates, clinical pregnancy rates (CPR) and live birth rates than the control group (62.5% vs. 45.3%, p = 0.038; 59.4% vs. 35.9%, p = 0.006 and 46.8% vs. 25%, p = 0.009). Fertile Chip had no effect on fertilization rates or embryo quality in male-factor infertility couples. However, the Fertile Chip group had a statistically higher pregnancy rate, CPR and live birth rate.

PMID:35263457 | DOI:10.1111/and.14415

Diabetes Care. 2022 Mar 9:dc212299. doi: 10.2337/dc21-2299. Online ahead of print.

ABSTRACT

OBJECTIVE: Despite the benefits of weight loss on metabolic profiles in patients with type 2 diabetes mellitus (T2DM), its association with myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause death remains elusive.

RESEARCH DESIGN AND METHODS: Using the National Health Insurance Service Database, we screened subjects who underwent general health checkups twice in a 2-year interval between 2009 and 2012. After identifying 1,522,241 patients with T2DM without a previous history of MI, IS, AF, and HF, we followed them until December 2018. Patients were stratified according to the magnitude of weight changes between two general health checkups: ≤ -10%, -10 to ≤ -5%, -5 to ≤5%, 5 to ≤10%, and >10%.

RESULTS: During the follow-up (median 7.0 years), 32,106 cases of MI, 44,406 cases of IS, 34,953 cases of AF, 68,745 cases of HF, and 84,635 all-cause deaths occurred. Patients with weight changes of -5 to ≤5% showed the lowest risk of each cardiovascular event. Both directions of weight change were associated with an increased cardiovascular risk. Stepwise increases in the risks of MI, IS, AF, HF, and all-cause death were noted with progressive weight gain (all P < 0.0001). Similarly, the more weight loss occurred, the higher the cardiovascular risks observed (all P < 0.0001). The U-shaped associations were consistently observed in both univariate and multivariate analyses. Explorative subgroup analyses also consistently showed a U-shaped association.

CONCLUSION: Both weight loss and gain >5% within a 2-year interval were associated with an increased risk of major cardiovascular events in patients with T2DM.

PMID:35263435 | DOI:10.2337/dc21-2299