Category: Nevin Manimala

Nat Commun. 2021 Mar 31;12(1):1990. doi: 10.1038/s41467-021-22156-6.

ABSTRACT

A crucial phase in the infection process, which remains poorly understood, is the localization of suitable host cells by bacteria. It is often assumed that chemotaxis plays a key role during this phase. Here, we report a quantitative study on how Salmonella Typhimurium search for T84 human colonic epithelial cells. Combining time-lapse microscopy and mathematical modeling, we show that bacteria can be described as chiral active particles with strong active speed fluctuations, which are of biological, as opposed to thermal, origin. We observe that there exists a giant range of inter-individual variability of the bacterial exploring capacity. Furthermore, we find Salmonella Typhimurium does not exhibit biased motion towards the cells and show that the search time statistics is consistent with a random search strategy. Our results indicate that in vitro localization of host cells, and also cell infection, are random processes, not involving chemotaxis, that strongly depend on bacterial motility parameters.

PMID:33790272 | DOI:10.1038/s41467-021-22156-6

Sci Adv. 2021 Mar 31;7(14):eabe7377. doi: 10.1126/sciadv.abe7377. Print 2021 Mar.

ABSTRACT

Whether the upper limb branch of Paleozoic “biramous” arthropods, including trilobites, served a respiratory function has been much debated. Here, new imaging of the trilobite Triarthrus eatoni shows that dumbbell-shaped filaments in the upper limb branch are morphologically comparable with gill structures in crustaceans that aerate the hemolymph. In Olenoides serratus, the upper limb’s partial articulation to the body via an extended arthrodial membrane is morphologically comparable to the junction of the respiratory book gill of Limulus and differentiates it from the typically robust exopod junction in Chelicerata or Crustacea. Apparently limited mechanical rotation of the upper branch may have protected the respiratory structures. Partial attachment of the upper branch to the body wall may represent an intermediate state in the evolution of limb branch fusion between dorsal attachment to the body wall, as in Radiodonta, and ventral fusion to the limb base, as in extant Euarthropoda.

PMID:33789898 | DOI:10.1126/sciadv.abe7377

Sci Adv. 2021 Mar 31;7(14):eabe9765. doi: 10.1126/sciadv.abe9765. Print 2021 Mar.

ABSTRACT

Advances in spectroscopy have the potential to improve our understanding of agricultural processes and associated trace gas emissions. We implement field-deployed, open-path dual-comb spectroscopy (DCS) for precise multispecies emissions estimation from livestock. With broad atmospheric dual-comb spectra, we interrogate upwind and downwind paths from pens containing approximately 300 head of cattle, providing time-resolved concentration enhancements and fluxes of CH₄, NH₃, CO₂, and H₂O. The methane fluxes determined from DCS data and fluxes obtained with a colocated closed-path cavity ring-down spectroscopy gas analyzer agree to within 6%. The NH₃ concentration retrievals have sensitivity of 10 parts per billion and yield corresponding NH3 fluxes with a statistical precision of 8% and low systematic uncertainty. Open-path DCS offers accurate multispecies agricultural gas flux quantification without external calibration and is easily extended to larger agricultural systems where point-sampling-based approaches are insufficient, presenting opportunities for field-scale biogeochemical studies and ecological monitoring.

PMID:33789900 | DOI:10.1126/sciadv.abe9765

BMJ Open Gastroenterol. 2021 Mar;8(1):e000501. doi: 10.1136/bmjgast-2020-000501.

ABSTRACT

OBJECTIVE: Severe acute pancreatitis (SAP) is associated with high mortality (15%-30%). Current guidelines recommend these patients are best managed in a multidisciplinary team setting. This study reports experience in the management of SAP within the UK’s first reported hub-and-spoke pancreatitis network.

DESIGN: All patients with SAP referred to the remote care pancreatitis network between 2015 and 2017 were prospectively entered onto a database by a dedicated pancreatitis specialist nurse. Baseline characteristics, aetiology, intensive care unit (ICU) stay, interventions, complications, mortality and follow-up were analysed.

RESULTS: 285 patients admitted with SAP to secondary care hospitals during the study period were discussed with the dedicated pancreatitis specialist nurse and referred to the regional service. 83/285 patients (29%; 37 male) were transferred to the specialist centre mainly for drainage of infected pancreatic fluid collections (PFC) in 95% (n=79) of patients. Among the patients transferred; 29 (35%) patients developed multiorgan failure with an inpatient mortality of 14% (n=12/83). The median follow-up was 18.2 months (IQR=11.25-35.51). Multivariate analysis showed that transferred patients had statistically significant longer overall hospital stay (p<0.001) but less ICU stay (p<0.012).

CONCLUSION: This hub-and-spoke model facilitates the management of the majority of patients with SAP in secondary care setting. 29% warranted transfer to our tertiary centre, predominantly for endoscopic drainage of PFCs. An evidence-based approach with a low threshold for transfer to tertiary care centre can result in lower mortality for SAP and fewer days in ICU.

PMID:33789915 | DOI:10.1136/bmjgast-2020-000501

BMJ. 2021 Mar 31;372:n693. doi: 10.1136/bmj.n693.

ABSTRACT

OBJECTIVE: To quantify rates of organ specific dysfunction in individuals with covid-19 after discharge from hospital compared with a matched control group from the general population.

DESIGN: Retrospective cohort study.

SETTING: NHS hospitals in England.

PARTICIPANTS: 47 780 individuals (mean age 65, 55% men) in hospital with covid-19 and discharged alive by 31 August 2020, exactly matched to controls from a pool of about 50 million people in England for personal and clinical characteristics from 10 years of electronic health records.

MAIN OUTCOME MEASURES: Rates of hospital readmission (or any admission for controls), all cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30 September 2020. Variations in rate ratios by age, sex, and ethnicity.

RESULTS: Over a mean follow-up of 140 days, nearly a third of individuals who were discharged from hospital after acute covid-19 were readmitted (14 060 of 47 780) and more than 1 in 10 (5875) died after discharge, with these events occurring at rates four and eight times greater, respectively, than in the matched control group. Rates of respiratory disease (P<0.001), diabetes (P<0.001), and cardiovascular disease (P<0.001) were also significantly raised in patients with covid-19, with 770 (95% confidence interval 758 to 783), 127 (122 to 132), and 126 (121 to 131) diagnoses per 1000 person years, respectively. Rate ratios were greater for individuals aged less than 70 than for those aged 70 or older, and in ethnic minority groups compared with the white population, with the largest differences seen for respiratory disease (10.5 (95% confidence interval 9.7 to 11.4) for age less than 70 years v 4.6 (4.3 to 4.8) for age ≥70, and 11.4 (9.8 to 13.3) for non-white v 5.2 (5.0 to 5.5) for white individuals).

CONCLUSIONS: Individuals discharged from hospital after covid-19 had increased rates of multiorgan dysfunction compared with the expected risk in the general population. The increase in risk was not confined to the elderly and was not uniform across ethnicities. The diagnosis, treatment, and prevention of post-covid syndrome requires integrated rather than organ or disease specific approaches, and urgent research is needed to establish the risk factors.

PMID:33789877 | DOI:10.1136/bmj.n693

Genetics. 2021 Mar 31;217(3):iyaa046. doi: 10.1093/genetics/iyaa046.

ABSTRACT

We propose an extended Gaussian mixture model for the distribution of causal effects of common single nucleotide polymorphisms (SNPs) for human complex phenotypes that depends on linkage disequilibrium (LD) and heterozygosity (H), while also allowing for independent components for small and large effects. Using a precise methodology showing how genome-wide association studies (GWASs) summary statistics (z-scores) arise through LD with underlying causal SNPs, we applied the model to GWAS of multiple human phenotypes. Our findings indicated that causal effects are distributed with dependence on total LD and H, whereby SNPs with lower total LD and H are more likely to be causal with larger effects; this dependence is consistent with models of the influence of negative pressure from natural selection. Compared with the basic Gaussian mixture model it is built on, the extended model-primarily through quantification of selection pressure-reproduces with greater accuracy the empirical distributions of z-scores, thus providing better estimates of genetic quantities, such as polygenicity and heritability, that arise from the distribution of causal effects.

PMID:33789345 | DOI:10.1093/genetics/iyaa046

Zhonghua Yi Xue Za Zhi. 2021 Mar 30;101(12):851-855. doi: 10.3760/cma.j.cn112137-20210111-00086.

ABSTRACT

Objective: To investigate the efficacy and safety of prophylactic intravenous (IV) administration of tranexamic acid (TXA) in abdominal aorta balloon-assisted pelvic tumor surgery. Methods: The data of patients who underwent abdominal aorta balloon-assisted pelvic tumor surgery in Peking University People’s Hospital from January 1, 2015 to December 31, 2019 were retrospectively collected. According to whether receiving the prophylactic use of TXA, the patients were divided into two groups: TXA group and control group. After propensity score matching based on age, gender and surgeon, 51 patients in TXA group and 51 patients in control group were allocated. The baseline, intraoperative and postoperative clinical data of the two groups were compared to explore the efficacy and safety of TXA. Results: A total of 525 cases undergoing abdominal aorta balloon-assisted pelvic surgery were enrolled from 2015 to 2019, of which 51 cases received prophylactic use of TXA, with a utilization rate of 9.7%. There were no significant differences in age [(40.7±15.1) years vs (38.2±14.5) years, P=0.393], gender (male: 51.0% vs 49.0%, P=0.843), body weight, body mass index (BMI), complications, American Society of Anesthesiologists (ASA) classification, hemoglobin, hemocrit (Hct), platelet, coagulation function-related indexes and tumor pathological types between the two groups (all P>0.05). Likewise, there were no significant differences in operation time, anesthesia time, cumulative time of balloon occlusion, intraoperative blood loss, intravenous fluid volume and blood transfusion volume between the two groups (all P>0.05). Additionally, there were no significant differences in postoperative ICU admission rate and length of hospital stay between the two groups (all P>0.05), and no venous thromboembolism (VTE) or death was reported. Compared with the control group, the rate of blood transfusion at 24 hours after operation in the TXA group was lower (41.2% vs 70.6%, P=0.003). The level of fibrinogen degradation products was lower [10.4 (6.1, 22.6) mg/L vs 13.2 (7.0, 24.7) mg/L], but the difference was not statistically significant (P=0.326). Conclusions: Prophylactic IV use of TXA does not reduce intraoperative bleeding in abdominal aorta balloon-assisted pelvic tumor surgery, but can decrease the rate of postoperative blood transfusion. No increased risk of postoperative TXA-related VTE was observed.

PMID:33789366 | DOI:10.3760/cma.j.cn112137-20210111-00086

Urol Int. 2021 Mar 31:1-6. doi: 10.1159/000513657. Online ahead of print.

ABSTRACT

INTRODUCTION: A history of transurethral surgery of the prostate is generally considered as a risk factor of adverse functional outcomes after radical prostatectomy (RP). We tested whether the risk of postoperative urinary incontinence (UIC) and erectile dysfunction (ED) after RP could be further substantiated in such patients.

MATERIALS AND METHODS: We tested the effect of the following variables on UIC and ED rates 1 year after RP: residual prostate volume after transurethral desobstruction, the time from transurethral desobstruction to RP, the type of transurethral desobstruction (TURP vs. laser enucleation), age, and nerve-sparing surgery (yes vs. no). UIC was defined as usage of any pad except a safety pad. ED was defined as no sexual intercourse possible.

RESULTS: Overall, 216 patients treated with RP between 2010 and 2019 in a tertiary care center were evaluated. All patients had previously undergone transurethral desobstruction. Regarding UIC analyses, only time from transurethral desobstruction to RP significantly influenced UIC rates (p = 0.003). Regarding ED rates, none of the tested variables reached statistical significance.

CONCLUSION: The risk of UIC and ED after RP is substantial in men who had previously undergone transurethral desobstruction. The time from transurethral desobstruction to RP significantly impacts on the postoperative UIC rates. This observation should be further explored in future studies.

PMID:33789314 | DOI:10.1159/000513657

Urol Int. 2021 Mar 31:1-6. doi: 10.1159/000514056. Online ahead of print.

ABSTRACT

INTRODUCTION: Numerous factors such as endothelial disease and hormonal disorder cause the development of erectile dysfunction (ED). However, the relationship between vitamin D deficiency (VDD) and ED is unclear. Moreover, the benefit of vitamin D replacement on ED patients with VDD is uncertain. As far as we know, there is no study yet in the literature regarding the addition of vitamin D to phosphodiesterase type 5 inhibitors in the treatment of ED patients with VDD. In this study, we investigated whether adding vitamin D to daily tadalafil treatment would be beneficial in ED patients with VDD.

METHODS: A total of 111 patients with VDD accompanying ED were retrospectively evaluated between January 2016 and December 2019. Patients were divided into 2 groups according to the treatment they received. Group 1 (n = 58) was treated with daily oral tadalafil 5 mg, while group 2 (n = 53) received oral tadalafil 5 mg and 4,000 IU vitamin D3. Total International Index of Erectile Function-15 (IIEF-15) scores and vitamin D levels of the groups were compared at the end of the study.

RESULTS: The mean vitamin D level was increased statistically significant in group 2, but no difference was seen in group 1 (p < 0.001 and p > 0.05, respectively). There was a significant increase in median erectile function, orgasmic function, sexual desire, sexual satisfaction, and overall satisfaction scores in both groups (p < 0.001). However, the increase in median erectile function and sexual desire scores was significantly higher in group 2 compared to group 1 at the end of the study (p = 0.01 and p < 0.001, respectively).

CONCLUSION: We found that adding vitamin D to 5 mg oral daily tadalafil treatment may have an additional positive effect on erectile function and sexual desire in ED patients with VDD.

PMID:33789318 | DOI:10.1159/000514056

Genetics. 2021 Mar 31;217(3):iyaa041. doi: 10.1093/genetics/iyaa041.

ABSTRACT

Ghost quantitative trait loci (QTL) are the false discoveries in QTL mapping, that arise due to the “accumulation” of the polygenic effects, uniformly distributed over the genome. The locations on the chromosome that are strongly correlated with the total of the polygenic effects depend on a specific sample correlation structure determined by the genotypes at all loci. The problem is particularly severe when the same genotypes are used to study multiple QTL, e.g. using recombinant inbred lines or studying the expression QTL. In this case, the ghost QTL phenomenon can lead to false hotspots, where multiple QTL show apparent linkage to the same locus. We illustrate the problem using the classic backcross design and suggest that it can be solved by the application of the extended mixed effect model, where the random effects are allowed to have a nonzero mean. We provide formulas for estimating the thresholds for the corresponding t-test statistics and use them in the stepwise selection strategy, which allows for a simultaneous detection of several QTL. Extensive simulation studies illustrate that our approach eliminates ghost QTL/false hotspots, while preserving a high power of true QTL detection.

PMID:33789342 | DOI:10.1093/genetics/iyaa041