Nevin Manimala

BMC Ecol Evol. 2022 Nov 30;22(1):140. doi: 10.1186/s12862-022-02091-w.

ABSTRACT

BACKGROUND: The number of interactions between a transferable gene or its protein product and genes or gene products native to its microbial host is referred to as connectivity. Such interactions impact the tendency of the gene to be retained by evolution following horizontal gene transfer (HGT) into a microbial population. The complexity hypothesis posits that the protein product of a transferable gene with lower connectivity is more likely to function in a way that is beneficial to a new microbial host compared to the protein product of a transferable gene with higher connectivity. A gene with lower connectivity is consequently more likely to be fixed in any microbial population it enters by HGT. The more recently proposed simplicity hypothesis posits that the connectivity of a transferable gene might increase over time within any single microbial population due to gene-host coevolution, but that differential rates of colonization of microbial populations by HGT in accordance with differences in connectivity might act to counter this and even reduce connectivity over time, comprising an evolutionary trade-off.

RESULTS: We present a theoretical model that can be used to predict the conditions under which gene-host coevolution might increase or decrease the connectivity of a transferable gene over time. We show that the opportunity to enter new microbial populations by HGT can cause the connectivity of a transferable gene to evolve toward lower values, particularly in an environment that is unstable with respect to the function of the gene’s protein product. We also show that a lack of such opportunity in a stable environment can cause the connectivity of a transferable gene to evolve toward higher values.

CONCLUSION: Our theoretical model suggests that the connectivity of a transferable gene can change over time toward higher values corresponding to a more sessile state of lower transferability or lower values corresponding to a more itinerant state of higher transferability, depending on the ecological milieu in which the gene exists. We note, however, that a better understanding of gene-host coevolutionary dynamics in natural microbial systems is required before any further conclusions about the veracity of the simplicity hypothesis can be drawn.

PMID:36451084 | DOI:10.1186/s12862-022-02091-w

BMC Cardiovasc Disord. 2022 Nov 30;22(1):511. doi: 10.1186/s12872-022-02891-4.

ABSTRACT

BACKGROUND: In the latest reports, atherogenic indices have been related to acute coronary syndromes, stable coronary artery disease, heart failure and future cardiac events. Conventional atherosclerosis risk factors have been associated with mitral annular calcification (MAC), but data on the relationship between atherogenic indices and MAC are lacking. We aimed to investigate a possible relationship between MAC and atherogenic indices.

METHODS: In total 741 patients (n = 427 with MAC and n = 314 without MAC) who were examined in our cardiology clinic from February 2016 to October 2021 were recruited in the study. Mitral annular calcification was diagnosed by transthoracic 2-dimensional echocardiography. The atherogenic coefficient (AC), Castelli risk index 1 (CRI-1), Castelli risk index 2 (CRI-2) and atherogenic index of plasma (AIP) were calculated by utilizing standard lipid test values.

RESULTS: There was no statistically significant difference in sex, age, diabetes and hypertension status between the patient and the control groups. Serum triglyceride level, AIP, Hs-CRP, smoking and BMI were independently significantly associated with MAC in multiple regression analysis (p < 0.001).

CONCLUSION: Higher AIP was related to the existence of MAC and also predict the presence of MAC independently. Studies evaluating the modification of these indices are needed.

PMID:36451082 | DOI:10.1186/s12872-022-02891-4

Rheumatol Ther. 2022 Dec 1. doi: 10.1007/s40744-022-00510-4. Online ahead of print.

ABSTRACT

INTRODUCTION: The association between diabetes mellitus (DM) and risk of osteoarthritis (OA) is inconsistent based on published observational studies. This study aimed to conduct a two-sample Mendelian randomization (MR) analysis to explore the causal link between glycated hemoglobin (HbA1c) level and OA risk.

METHODS: Genome-wide association studies (GWAS) summary statistics were obtained from the publicly available Integrative Epidemiology Unit (IEU) OpenGWAS database. A series of screening processes were performed to select qualified instrumental single-nucleotide polymorphisms (SNPs) strongly related to exposure. The inverse-variance-weighted method, weighted-median method, and MR-Egger method were performed to ensure robust and reliable results. The MR-Egger intercept test, Cochran’s Q test, and the leave-one-out sensitivity analysis were utilized to assess the horizontal pleiotropy, heterogeneities, and stability of these genetic variants for OA. Odds ratio (OR) and 95% confidence interval (CI) were calculated.

RESULTS: MR analyses found a robust causal association of genetically determined HbA1c with knee OA (OR = 1.561; 95% CI 1.110-2.197; P = 0.011), but not with hip OA (OR = 1.073; 95% CI 0.674-1.710; P = 0.766) or overall OA (OR = 1.141; 95% CI 0.904-1.441; P = 0.804). Sensitivity analyses showed that there was a strong association between SNPs and HbA1c (F = 21.138), no evidence of heterogeneity (Q = 150.625, P = 0.402), and no potential SNPs affecting the causal link.

CONCLUSION: Our MR study supported a causal effect of genetically increased HbA1c on knee OA risk.

PMID:36451030 | DOI:10.1007/s40744-022-00510-4

Cancer Chemother Pharmacol. 2022 Dec 1. doi: 10.1007/s00280-022-04495-3. Online ahead of print.

ABSTRACT

PURPOSE: The current idea of how oral mucositis (OM) develops is primarily based on hypotheses and the early events which precede clinically established OM remain to be demonstrated. Cryotherapy (CT) continues to have considerable promise in clinical settings to reduce chemotherapy-induced OM. Although being effective, the knowledge is scarce regarding the ideal temperature for prevention of OM. Thus, the present study had two main objectives: (i) to develop an animal model to investigate the early events of OM; (ii) to study at what cooling temperature these early events could be abolished.

METHODS: Male Sprague-Dawley rats were anaesthetized and given an intravenous bolus dose with the cytostatic drug fluorouracil (5-FU). During the first hour following injection with 5-FU, the oral cavity of the rats was cooled to a mucosal temperature at the range of 15-30 ^○C, or left uncooled (35 ^○C), serving as control. After 3-5 days, the rats were euthanized, and the buccal mucosa was excised. Subsequently, mucosal thickness and expression of IL-6 and TNF-α were analyzed with immunohistochemistry and enzyme-linked immunosorbent assay (ELISA).

RESULTS: Five days following treatment with 5-FU, a statistically significant thickening of the oral mucosa occurred, and a distinct expression of both IL-6 and TNF-α were observed. The cryo-treated groups (15-30 °C) displayed statistically significantly thinner mucosa as compared to the control group (35 °C). The ELISA showed an increase in expression of the proinflammatory cytokines IL-6 and TNF-α in tissues exposed to 5-FU that were treated with increasing temperatures (15-30 °C).

CONCLUSION: Bolus i.v. injection with 5-FU in rats can be used to create a functional animal model for chemotherapy-induced OM. Further, moderate temperature reduction is sufficient to reduce the early events which may precede clinically established OM.

PMID:36451020 | DOI:10.1007/s00280-022-04495-3

Cardiovasc Intervent Radiol. 2022 Nov 30. doi: 10.1007/s00270-022-03300-1. Online ahead of print.

ABSTRACT

PURPOSE: To assess occlusion success and adverse events associated with the use of a self-expanding device for peripheral artery embolization.

METHODS: This prospective, single-arm, feasibility study was conducted using the Caterpillar™ Arterial Embolization Device composed of opposing nitinol fibers and a flow-occluding membrane. Twenty patients (24 embolization sites) were treated at four investigational centers in New Zealand and Australia and followed for 30 days. Embolization sites included mesenteric, accessory renal, and iliac arteries and their branches. Primary outcome measures were peri-procedural occlusion confirmed by angiography and freedom from device-related serious adverse events (SAEs) at 30 days. Secondary observations included time to occlusion and assessment of adverse events.

RESULTS: Peri-procedural occlusion was 100%, and freedom from a device-related SAE was 94.7% at 30 days. One patient had abdominal bloating that required hospitalization deemed possibly related to the device or procedure. Twenty-two of 24 embolization sites were occluded with one device (91.7%). Mean procedure duration was 11.7 ± 8.6 min (device deployment time: 1.8 ± 1.0 min), and mean fluoroscopy time was 241 ± 290.7 s. All embolization sites occluded during the procedure with 62.5% occluded within three minutes and 91.6% occluded within ten minutes. No devices migrated or required re-embolization. Freedom from device- and procedure-related adverse events was 84.2%. One patient died from aortic rupture during a subsequent adjunctive abdominal aortic endovascular procedure deemed unrelated to the embolization device or procedure.

CONCLUSIONS: This first-in-human study of the Caterpillar embolization device achieved peri-procedural occlusion in all patients with a 94.7% freedom from device-related SAE at 30 days.

LEVEL OF EVIDENCE: Level 2b-prospective, multicenter, single-arm, first-in-human clinical study. Pre-specified endpoints were analyzed using descriptive statistics.

PMID:36450994 | DOI:10.1007/s00270-022-03300-1

J Comput Biol. 2022 Nov 25. doi: 10.1089/cmb.2022.0181. Online ahead of print.

ABSTRACT

The complex mechanisms of diseases involve the disturbance of the molecular network, rather than disorder in a single gene, implying that single gene-based analysis is insufficient to understand these mechanisms. Gene regulatory networks (GRNs) have attracted a lot of interest and various approaches have been developed for their statistical inference and gene network-based analysis. Although various computational methods have been developed, relatively little attention has been paid to incorporation of biological knowledge into the computational approaches. Furthermore, existing studies on network-based analysis perform prediction/classification of status of cell lines based on preconstructed GRNs, implying that we cannot extract prediction/classification-specific gene networks, leading to difficulty in interpretation of biological mechanisms and marker identification related to the status of cancer cell lines. We developed a novel strategy to build a GRN-based classifier, called a GRN-classifier. The proposed GRN-classifier estimates GRNs and classifies cell lines simultaneously, where the gene network is estimated to minimize error in gene network estimation and the negative log-likelihood for classifying cell lines. Thus, we can identify biological status-specific gene regulatory systems, enabling us to achieve biologically reliable interpretation of the classification. We also propose an algorithm to implement the GRN-classifier based on coordinate descent update. Monte Carlo simulations were conducted to examine performance of the GRN-classifier. Results: Our strategy provides effective results in feature selection in the classification model and edge selection in gene network estimation. The GRN-classifier also shows outstanding classification accuracy. We apply the GRN-classifier to classify cancer cell lines into anticancer drug-related status, that is, 5-fluorouracil (5-FU)-sensitive/resistant and 5-FU target/nontarget cancer cell lines. We then identified 5-FU markers based on 5-FU-related status classification-specific gene networks. The mechanisms of the identified markers were verified through literature survey. Our results suggest that the molecular interplay between MYOF and AHNAK2 may play a crucial role in drug resistance and can provide information on the chemotherapy efficiency of 5-FU. It is also suggested that suppression of the identified 5-FU markers, including MYOF/AHNAK2 and AKR1C1/AKR1C3 may improve 5-FU resistance of cancer cell lines.

PMID:36450117 | DOI:10.1089/cmb.2022.0181

Breastfeed Med. 2022 Nov 24. doi: 10.1089/bfm.2022.0211. Online ahead of print.

ABSTRACT

Purpose: Breast milk iodine concentration (BMIC) from vegan and vegetarian lactating mothers has not previously been evaluated. The goal of this study was to assess BMIC from vegans, vegetarians, and omnivores and to assess intake of iodine by breastfed infants. Materials and Methods: Breast milk samples from vegans (n = 12), vegetarians (n = 6), and omnivores (n = 12) living in the United States were analyzed. BMIC was determined at the mass-to-charge ratio (m/z) 127 by inductively coupled plasma mass spectrometry (ICP-MS) using an Agilent 8800 ICP-MS/MS (Agilent Technologies). Results: There was a significant difference in mean BMIC between participants following a plant-based diet (vegan and vegetarian, n = 18) compared with omnivores [4.42 versus 5.02 Ln(BMIC), respectively; p = 0.0405]. In linear regression to predict BMIC, vegan diet was a negative predictor (standardized β = -0.409) and use of multi- or prenatal supplements was a positive predictor (standardized β = 0.319). There were differences in the percentage of inadequate BMIC per maternal diet (75% vegan, 67% vegetarian, omnivore 58%) but this did not reach statistical significance. In 67% of the samples (20/30) BMIC was lower than the National Academy of Medicine’s adequate intake (AI), assuming infant milk consumption of 0.78 L/day. Conclusions: Most samples from vegans and vegetarians contained a lower BMIC than AI for infants 0-6 months. Counseling of pregnant vegans and vegetarians should highlight importance of iodine supplementation during lactation. The findings are based on a small number of samples, especially for vegetarians, and thus, they need to be confirmed by larger studies.

PMID:36450113 | DOI:10.1089/bfm.2022.0211

Telemed J E Health. 2022 Nov 24. doi: 10.1089/tmj.2022.0242. Online ahead of print.

ABSTRACT

Introduction: The COVID-19 pandemic accelerated the adoption of telemedicine services for the delivery of outpatient neurological care. We sought to understand perceptions and the acceptance of this technology by neurology specialists during the proliferation of telemedicine services into their outpatient practices. Methods: We adapted the Telehealth Usability Questionnaire for neurological care via telemedicine. Our 29-item questionnaire evaluated the telemedicine system in three domains: quality of the telemedicine platform, ability to conduct a sufficient neurological examination, and overall system confidence. The survey was distributed to 88 clinical neurology faculty in the Johns Hopkins Health System. Responses were collapsed into “Favorable,” “Neutral,” and “Unfavorable.” Within each domain, responses to individual questions were analyzed by neurology subspecialty using descriptive statistics. Results: We received completed surveys from 46 of the 88 (52%) neurology faculty. Of those, most reported favorable comfort with the current platform (98%), ease of use (73%), and quality (80%). However, responses indicated only average ability to troubleshoot telemedicine platform issues when they occurred (55%) and to complete an entire neurological examination (52%). Subspecialty comparisons revealed differences in diagnostic confidence; 30% of neuromuscular faculty indicated that they could make accurate neurological diagnoses through a tele-examination as opposed to ≥84% for other specialties. Conclusions: The use of telemedicine services for the delivery of outpatient neurological care is feasible and acceptable to most neurologists, although diagnostic confidence compared with in-person visits may be reduced and differs by subspecialty. Improvements in technological infrastructure and care models are needed to advance telemedicine neurological care delivery. Our data also suggest that a larger multicenter investigation of telemedicine use post-pandemic would be useful.

PMID:36450111 | DOI:10.1089/tmj.2022.0242

Plast Aesthet Nurs (Phila). 2022 Jul-Sep 01;42(3):156-162. doi: 10.1097/PSN.0000000000000442.

ABSTRACT

One of the most common complications associated with a diaphyseal humeral fracture is the development of a radial nerve injury. We conducted a study to analyze the degree of recovery and prognostic factors associated with radial nerve palsy in patients with diaphyseal humerus fractures. We retrospectively analyzed 28 patients who presented to the Hospital La Fe, Valencia, Spain, with a diaphyseal humerus fracture associated with radial nerve injury between 2010 and 2020. A total of 14.3% (n = 4) of the patients in our cohort had open fractures and 85.7% (n = 24) had closed fractures. There were no statistically significant differences between the type of treatment and the type of fracture (p = .13). There were also no significant differences between the type of treatment and recovery time (p = .42). There was a statistically significant difference (p = .04) in the mean recovery time for patients with preoperative radial nerve injuries (11.9 months) compared with patients who sustained a radial nerve injury secondary to surgical repair of the fracture (8.6 months). The difference in recovery time between patients with open and closed fractures was not statistically significant (p = .3). Results of the study showed that the type of fracture (i.e., open or closed) did not affect radial nerve palsy recovery time. Patients who sustain radial nerve injuries secondary to a surgical repair have a shorter recovery time than patients who sustain primary radial nerve injuries.

PMID:36450058 | DOI:10.1097/PSN.0000000000000442

Plast Aesthet Nurs (Phila). 2022 Jul-Sep 01;42(3):152-155. doi: 10.1097/PSN.0000000000000440.

ABSTRACT

The ability to achieve a good functional outcome, quality of life, and patient satisfaction related to the donor site of free flaps is an important factor in flap selection. One of the main advantages of an anterolateral thigh (ALT) free flap is its minimal donor-site morbidity. We conducted a study to analyze healing of ALT flap donor sites based on the type of closure. A total of 65 patients were included in the study. We divided the participants into two cohorts (i.e., primary closure [n = 51] and skin grafting [n = 14]). There were no statistically significant differences between the two cohorts relative to age, gender, or risk factors for wound healing (e.g., tobacco use, obesity, diabetes mellitus, and cardiovascular disease). We found there was a statistically significant difference (p < .05) between the mean donor-site wound healing time in the primary closure group (n = 51; 22.41 days [±9.94]) compared with the skin grafting group (n = 14; 54.57 days [±21.59]). To reduce wound healing time, improve cosmetic results, and increase functional outcomes in patients undergoing ALT free flap, we recommend using primary closure for the donor sites and avoiding skin grafting whenever possible.

PMID:36450057 | DOI:10.1097/PSN.0000000000000440