Nevin Manimala

J Gastroenterol Hepatol. 2021 Mar 23. doi: 10.1111/jgh.15504. Online ahead of print.

ABSTRACT

BACKGROUND: Quinolones are globally popular antibiotics with proven potency, broad coverage and reasonable safety. However, some concerns were raised as to their possible association with acute liver failure (ALF).

OBJECTIVE: To assess ALF risk within 30 days of receiving a systemically administered quinolone antibiotic, in individuals with no history of liver/diseases.

METHODS: We conducted a nested case-control study using electronic health records from the Cerner Health Facts®. The initial cohort (n= 35,349,943) included all patients who were admitted between 2000-2016, with no history of liver diseases, and had a minimum medical history of one year. Eligible cases were inpatients who were first diagnosed with ALF between 2010-2015. Using incidence density sampling, each case was matched with up to five unique controls by sex, race, age at index encounter, and period-at-risk. We used conditional logistic regression to calculate the ORs and 95% CI for ALF risk, upon adjusting for exposure to other medications, and major confounders (diabetes mellitus and alcohol abuse). We used the STROBE Statement for reporting on our study.

RESULTS: We identified 3,151 cases and 15,657 controls. Our primary analysis did not reveal an association between quinolones and ALF risk. However, some risk was identified among those with no or few comorbidities, those ≤60 years of age, women, men, African Americans and Caucasians.

CONCLUSION: Although our study does not suggest an overall association between quinolones and ALF, elevated risks seen in some subgroups warrant further investigation.

PMID:33755266 | DOI:10.1111/jgh.15504

Andrologia. 2021 Mar 23:e14030. doi: 10.1111/and.14030. Online ahead of print.

ABSTRACT

Lumbosacral pathologies can lead to infertility. Onuf’s nucleus changes in these pathologies may have a role in low sperm number. This study aims to investigate the relationship between Onuf’s nucleus degeneration and sperm number following spinal subarachnoid haemorrhage. 22 rabbits were used. They were divided into three groups; five of them were used as the control (GI), five as the SHAM (GII) and twelve as the study groups (GIII). The study group received 0.7 ccs autologous blood into the spinal subarachnoid space at the T12-L1 level. After two weeks, all animals were decapitated, and S1-S3 laminectomy was done. Neurodegenerative changes of Onuf’s nucleus, pudendal ganglia (S3) following two weeks after spinal SAH, were examined; sperm numbers were calculated. Degenerated neuron density of the Onuf’s nucleus (n/mm³ ), the pudendal ganglia (S3) (n/mm³ ) and mean sperm numbers were calculated as 5 ± 2, 8 ± 3/mm³ and 98.345 ± 12.776/mm³ in the control (GI), 20 ± 5/mm³ , 243 ± 66/mm³ and 91.841 ± 9.654/mm³ in the SHAM (GII), 143 ± 39/mm³ , 2,350 ± 320/mm³ and 68.549 ± 5.540/mm³ in the study group (GIII). In conclusion, there were statistically significant differences between groups. Onuf’s nucleus may be responsible for decreased sperm number following spinal SAH.

PMID:33755239 | DOI:10.1111/and.14030

Community Dent Oral Epidemiol. 2021 Mar 23. doi: 10.1111/cdoe.12631. Online ahead of print.

ABSTRACT

OBJECTIVES: Despite great efforts to improve paediatric dental care access in the last two decades, the use of emergency departments (ED) for dental conditions among children that are more appropriately addressed in dental offices remains a public health concern in the United States. We examined factors associated with ED visits for nontraumatic dental conditions or NTDCs and ED visits for any other reason among children and adolescents.

METHODS: A retrospective secondary data analysis of ED visits was conducted using the 2014-2015 Nationwide Emergency Department Sample (NEDS) data. NTDCs were further categorized as diseases of hard tissue (eg dental caries), pulp/periapical (eg root canal infections), gingival/periodontal (eg conditions that affect the supporting tissues) and other. We included patient/socioeconomic characteristics, disposition, time of visit, and the Grouped Charlson Comorbidity Index (GRPCI) in our analysis. Bivariate associations were tested using chi-squared test (α = 0.05).

RESULTS: There were 70 616 194 ED visits in 2014-15, with 465 353 (0.7%) visits for NTDCs. Statistically significant differences were observed for all patient characteristics tested, except for gender when comparing children visiting the ED for NTDCs and children visiting for any other reason. Medicaid was the expected payer for nearly 60% of all ED visits, and the uninsured shared a larger proportion of NTDC visits (19.4%) than other visits (8.8%). Late adolescents (aged 18-21) accounted for over 50% of NTDC visits but only one-fifth of all other types of ED visits. Late adolescents (18-21 years old) who were uninsured had a significantly higher proportion of NTDC visits. Of all NTDC visits, 19.1% were related to hard tissue disease, 25.3% pulp/periapical, 7.9% periodontal disease, and the remaining were grouped as other dental diseases.

CONCLUSIONS: The ED use for NTDCs is more common among late adolescents, Medicaid and uninsured groups. Examining and implementing new approaches that improve access to routine dental care for these groups may help in reducing inefficient ED use related to NTDCs.

PMID:33755217 | DOI:10.1111/cdoe.12631

Physiol Plant. 2021 Mar 23. doi: 10.1111/ppl.13402. Online ahead of print.

ABSTRACT

Drought stress hinders the growth and development of crop plants and ultimately, its productivity. It is expected that drought stress will be frequent and intense in the future due to drastic changes in the global climate. It is necessary to make crop plants more resilient to drought stress through various techniques; drought-hardening is one of them. Defining various metabolic strategies used by tobacco plants to confer drought tolerance will be important for maintaining plant physiological functions, but studies addressing this topic are limited. This study was designed to elucidate the drought tolerance and adaptation strategies used by tobacco via the application of different circular drought-hardening cycles (control: no drought-hardening, T1: one cycle of drought hardening, T2: two cycles of drought-hardening, and T3: three cycles of drought-hardening) to two tobacco varieties namely Honghuadajinyuan (H) and Yun Yan-100 (Y). The results revealed that drought-hardening decreased the fresh and dry biomass of the plant. The decrease was more pronounced in the T3 treatment for both H (23 and 29%, respectively) and Y (26 and 31%, respectively) under drought stress. The MDA contents, especially in T1 and T2 in both varieties, were statistically similar compared with control under drought stress. Similarly, higher POD, APX, and GR activities were observed, especially in T3, and elevated amounts of AsA and GSH were also observed among the different circular drought-hardening treatments under drought stress. Thus drought-hardening mitigated the oxidative damage by increasing the antioxidant enzyme activities and elevated the content of antioxidant substances, a key metabolic strategy under drought stress. Similarly, another important plant metabolic strategy is the osmotic adjustment. Different drought-hardening treatments improved the accumulation of proline and soluble sugars contents which contributed to osmoregulation. Finally, at the molecular level circular drought-hardening improved the transcript levels of antioxidant enzyme-related genes (CAT, APX1, and GR2), proline and polyamines biosynthesis-related genes (P5CS1 and ADC2), and ABA signalling (SnRK2), and transcription factors (AREB1 and WRKY6) in response to drought stress. As a result, circular drought-hardening (T2 and T3 treatments) promoted tolerance to water stress via affecting the anti-oxidative capacity, osmotic adjustment, and regulation of gene expression in tobacco.

PMID:33755204 | DOI:10.1111/ppl.13402

J Cell Physiol. 2021 Mar 23. doi: 10.1002/jcp.30367. Online ahead of print.

ABSTRACT

The evolution of the SARS-CoV-2 new variants reported to be 70% more contagious than the earlier one is now spreading fast worldwide. There is an instant need to discover how the new variants interact with the host receptor (ACE2). Among the reported mutations in the Spike glycoprotein of the new variants, three are specific to the receptor-binding domain (RBD) and required insightful scrutiny for new therapeutic options. These structural evolutions in the RBD domain may impart a critical role to the unique pathogenicity of the SARS-CoV-2 new variants. Herein, using structural and biophysical approaches, we explored that the specific mutations in the UK (N501Y), South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y), and hypothetical (N501Y-E484K) variants alter the binding affinity, create new inter-protein contacts and changes the internal structural dynamics thereby increases the binding and eventually the infectivity. Our investigation highlighted that the South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y) variants are more lethal than the UK variant (N501Y). The behavior of the wild type and N501Y is comparable. Free energy calculations further confirmed that increased binding of the spike RBD to the ACE2 is mainly due to the electrostatic contribution. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection-driven epistasis in protein evolution. The triple mutants (South African and Brazilian) may pose a serious threat to the efficacy of the already developed vaccine. Our analysis would help to understand the binding and structural dynamics of the new mutations in the RBD domain of the Spike protein and demand further investigation in in vitro and in vivo models to design potential therapeutics against the new variants.

PMID:33755190 | DOI:10.1002/jcp.30367

J Anim Sci. 2021 Mar 23:skab090. doi: 10.1093/jas/skab090. Online ahead of print.

ABSTRACT

Two experiments determined the effects of crude protein (CP) in diets containing coarse wheat bran (CWB) with or without pharmacological levels of Zn on weanling pig growth performance. In Exp. 1, treatments included a positive control (21% CP) with 3,000 mg/kg Zn in phase 1 and 2,000 mg/kg in phase 2; negative control (21% CP) with 110 mg/kg Zn, and four diets containing 4% CWB and 110 mg/kg Zn formulated to 21, 19.5, 18, or 16.5% CP. The three diets with 21% CP and CWB contained 1.40% standardized ileal digestible (SID) Lys in phase 1 and 1.35% SID Lys in phase 2, while the 19.5, 18, and 16.5% CP diets contained 1.35, 1.25 and 1.20% Lys, respectively. Pigs fed the diet containing pharmacological Zn had increased (P < 0.05) ADG and G:F compared to the negative control and the 21% CP CWB diet. Reducing CP decreased ADG and G:F (linear, P = 0.002). In Exp. 2, diets consisted of: 1) positive control with 2,000 mg/kg of Zn and 21% CP (1.35% SID Lys); 2) 110 mg/kg Zn and 21% CP; and 3 diets with 110 mg/kg Zn and 18% CP with 3) 1.2% SID Lys; 4) 1.35% SID Lys by the addition of crystalline AA, and 5) diet 4 with added non-essential AA. Pigs fed 21% CP with Zn had increased (P = 0.001) ADG compared to those fed 18% CP (1.35% SID Lys) or 1.2% SID Lys. In summary, added Zn improved growth performance, but reducing CP did not.

PMID:33755175 | DOI:10.1093/jas/skab090

Eur J Prev Cardiol. 2021 Mar 23;28(1):8-17. doi: 10.1177/2047487320939217.

ABSTRACT

AIMS: To evaluate the effect of linagliptin on left ventricular systolic function beyond glycaemic control in type 2 diabetes mellitus.

METHODS AND RESULTS: A multicentre, randomised, double-blind, placebo controlled, parallel-group study, was performed (the DYDA 2 trial). Individuals with type 2 diabetes mellitus and asymptomatic impaired left ventricular systolic function were randomly allocated in a 1:1 ratio to receive for 48 weeks either linagliptin 5 mg daily or placebo, in addition to their diabetes therapy. Eligibility criteria were age 40 years and older, haemoglobin A1c 8.0% or less (≤64 mmol/mol), no history of cardiac disease, concentric left ventricular geometry (relative wall thickness ≥0.42), impaired left ventricular systolic function defined as midwall fractional shortening 15% or less at baseline echocardiography. The primary end point was the modification of midwall fractional shortening over time. The main secondary objectives were changes in diastolic and/or in longitudinal left ventricular systolic function as measured by tissue Doppler echocardiography. One hundred and eighty-eight patients were enrolled, predominantly men with typical insulin-resistance comorbidities. At baseline, mean midwall fractional shortening was 13.3%±2.5. At final evaluation, 88 linagliptin patients and 86 placebo patients were compared: midwall fractional shortening increased from 13.29 to 13.82 (+4.1%) in the linagliptin group, from 13.58 to 13.84 in the placebo group (+1.8%, analysis of covariance P = 0.86), corresponding to a 2.3-fold higher increase in linagliptin than the placebo group, although non-statistically significant. Also, changes in diastolic and longitudinal left ventricular systolic function did not differ between the groups. Serious adverse events or linagliptin/placebo permanent discontinuation occurred in very few cases and in the same percentage between the groups.

CONCLUSIONS: In the DYDA 2 patients the addition of linagliptin to stable diabetes therapy was safe and provided a modest non-significant increase in left ventricular systolic function measured as midwall fractional shortening.

TRIAL REGISTRATION NUMBER: ClinicalTrial.gov (ID NCT02851745).

PMID:33755143 | DOI:10.1177/2047487320939217

Europace. 2021 Mar 23:euab028. doi: 10.1093/europace/euab028. Online ahead of print.

ABSTRACT

AIM: The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims.

METHODS AND RESULTS: Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P < 0.0001) after adjusting for PADIT score. A Harrell’s C-statistic for the PADIT score and history of prior CIED infection was 0.76.

CONCLUSION: The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.

PMID:33755136 | DOI:10.1093/europace/euab028

Int J Epidemiol. 2021 Mar 23:dyab036. doi: 10.1093/ije/dyab036. Online ahead of print.

ABSTRACT

BACKGROUND: Rigorous evaluation of the calibration and discrimination of breast-cancer risk-prediction models in prospective cohorts is critical for applications under clinical guidelines. We comprehensively evaluated an integrated model incorporating classical risk factors and a 313-variant polygenic risk score (PRS) to predict breast-cancer risk.

METHODS: Fifteen prospective cohorts from six countries with 239 340 women (7646 incident breast-cancer cases) of European ancestry aged 19-75 years were included. Calibration of 5-year risk was assessed by comparing expected and observed proportions of cases overall and within risk categories. Risk stratification for women of European ancestry aged 50-70 years in those countries was evaluated by the proportion of women and future cases crossing clinically relevant risk thresholds.

RESULTS: Among women <50 years old, the median (range) expected-to-observed ratio for the integrated model across 15 cohorts was 0.9 (0.7-1.0) overall and 0.9 (0.7-1.4) at the highest-risk decile; among women ≥50 years old, these were 1.0 (0.7-1.3) and 1.2 (0.7-1.6), respectively. The proportion of women identified above a 3% 5-year risk threshold (used for recommending risk-reducing medications in the USA) ranged from 7.0% in Germany (∼841 000 of 12 million) to 17.7% in the USA (∼5.3 of 30 million). At this threshold, 14.7% of US women were reclassified by adding the PRS to classical risk factors, with identification of 12.2% of additional future cases.

CONCLUSION: Integrating a 313-variant PRS with classical risk factors can improve the identification of European-ancestry women at elevated risk who could benefit from targeted risk-reducing strategies under current clinical guidelines.

PMID:33755131 | DOI:10.1093/ije/dyab036

J Natl Cancer Inst. 2021 Mar 23:djab049. doi: 10.1093/jnci/djab049. Online ahead of print.

ABSTRACT

Today, there are more than 16.9 million cancer survivors in the United States; this number is projected to grow to 22.2 million by 2030. While much progress has been made in understanding cancer survivors needs and in improving survivorship care since the seminal 2006 Institute of Medicine report From Cancer Patient to Cancer Survivor: Lost in Transition, there is a need to identify evidence gaps and research priorities pertaining to cancer survivorship. Thus, in April 2019, the National Cancer Institute convened grant-funded extramural cancer survivorship researchers, representatives of professional organizations, cancer survivors, and advocates for a one-day in-person meeting. At this meeting, and in a subsequent webinar aimed at soliciting input from the wider survivorship community, evidence gaps and ideas for next steps in the following six areas, identified from the 2006 Institute of Medicine report, were discussed: surveillance for recurrence and new cancers, management of long-term and late physical effects, management of long-term and late psychosocial effects, health promotion, care coordination, and financial hardship. Identified evidence gaps and next steps across the areas included the need to understand and address disparities among cancer survivors, to conduct longitudinal studies as well as longer-term (>5 years post-diagnosis) follow-up studies, to leverage existing data, and to incorporate implementation science strategies to translate findings into practice. Designing studies to address these broad evidence gaps, as well as those identified in each area, will expand our understanding of cancer survivors’ diverse needs, ultimately leading to the development and delivery of more comprehensive evidence-based quality care.

PMID:33755126 | DOI:10.1093/jnci/djab049