Nevin Manimala

Nucleic Acids Res. 2022 Oct 16:gkac879. doi: 10.1093/nar/gkac879. Online ahead of print.

ABSTRACT

Antimicrobial toxins help prokaryotes win competitive advantages in intraspecific or interspecific conflicts and are also a critical factor affecting the pathogenicity of many pathogens that threaten human health. Although many studies have revealed that antagonism based on antimicrobial toxins plays a central role in prokaryotic life, a database on antimicrobial toxins remains lacking. Here, we present the prokaryotic antimicrobial toxin database (PAT, http://bioinfo.qd.sdu.edu.cn/PAT/), a comprehensive data resource collection on experimentally validated antimicrobial toxins. PAT has organized information, derived from the reported literature, on antimicrobial toxins, as well as the corresponding immunity proteins, delivery mechanisms, toxin activities, structural characteristics, sequences, etc. Moreover, we also predict potential antimicrobial toxins in prokaryotic reference genomes and show the taxonomic information and environmental distribution of typical antimicrobial toxins. These details have been fully incorporated into the PAT database, where users can browse, search, download, analyse and view informative statistics and detailed information. PAT resources have already been used in our prediction and identification of prokaryotic antimicrobial toxins and may contribute to promoting the efficient investigation of antimicrobial toxin functions, the discovery of novel antimicrobial toxins, and an improved understanding of the biological roles and significance of these toxins.

PMID:36243963 | DOI:10.1093/nar/gkac879

Iran J Allergy Asthma Immunol. 2022 Aug 12;21(4):441-448. doi: 10.18502/ijaai.v21i4.10291.

ABSTRACT

Schizophrenia (SCZ) is a debilitating mental disorder with various causes involving complex interactions between genetic factors and environmental agents. The immune system plays a vital role in the pathology and function of the nervous system. Interleukin 35 (IL-35) is a regulatory and anti-inflammatory cytokine that can prevent autoimmune and inflammatory diseases. This study aimed to investigate the role of autoantibodies against some central nervous system (CNS) antigens and IL-35 serum levels in patients with Schizophrenia. This case-control study involved 80 participants. The serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the autoantibodies in the CNS by indirect immunofluorescence assay (IFA). The serum levels of IL-35 were decreased in patient groups compared to healthy subjects. Autoantibodies against N-methyl-D-aspartate receptor (NMDAR) and myelin-associated glycoprotein (MAG) were positive in 15% (6/40) and 7.5% (3/40), respectively; however, no antibodies against myelin, aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), voltage-gated potassium channel (VGKC), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), γ-butyric acid receptor type B1 γ-butyric acid receptor type B1 (GABABR), antidipeptidyl peptidase-like protein-6 (DPPX), immunoglobulin-like cell adhesion molecule 5 (IgLON5), Glycine receptor (R) and acetylcholine receptor (Ach R) were detected (No statistics were computed). We found that decreased serum IL-35 levels and the existence autoantibodies against NMDAR antigen may contribute to the pathogenesis of SCZ.

PMID:36243932 | DOI:10.18502/ijaai.v21i4.10291

Aerosp Med Hum Perform. 2022 Oct 1;93(10):739-745. doi: 10.3357/AMHP.6072.2022.

ABSTRACT

INTRODUCTION: Fatigue has negative effects on flight safety, especially in military aviation, where missions are often performed under challenging conditions. Modafinil is a relatively new pharmaceutical able to counter the symptoms of fatigue, but efficacy has not yet been studied in operational military aviation. This study aims to establish effectiveness and safety of modafinil in military operations.METHODS: This field study was conducted during deployment in the Middle East by the Royal Netherlands Air Force fighter pilots. Prior to use operationally, pilots had to complete a 24-h ground test in which modafinil was administered during a nonflying period using a questionnaire to screen for duty-relevant side effects. If no side effects were reported, operational usage was allowed. In addition to registration of modafinil’s effects, relevant data prior to and after administration were recorded, including caffeine consumption and sleep afterwards.RESULTS: Of the 75 pilots who completed ground testing, only one experienced duty-relevant side effects. Modafinil was used in 192 operational flights, mostly during night-time. In 128 (67%) of the flights, modafinil was used preventively, in 64 (33%) because of fatigue. In 182 (95%) of the flights, positive effects of modafinil were reported, with a maximum effect 2-3 h after administration. There was no statistical correlation between modafinil’s beneficial effects and prior administration of caffeine or sleep medication, nor was sleep afterwards negatively affected.DISCUSSION: This study indicates modafinil is a suitable pharmaceutical countermeasure to minimize the effects of fatigue during real-life fighter operations, without signs of negative impact on flight safety or sleep quality afterwards.Wingelaar-Jagt YQ, Wingelaar TT, Riedel WJ, Ramaekers JG. Subjective effects of modafinil in military fighter pilots during deployment. Aerosp Med Hum Perform. 2022; 93(10):739-745.

PMID:36243913 | DOI:10.3357/AMHP.6072.2022

Obes Surg. 2022 Oct 15. doi: 10.1007/s11695-022-06318-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Visible light spectroscopy (VLS) represents a sensitive, non-invasive method to quantify tissue oxygen levels and detect hypoxemia. The aim of this study was to assess the microperfusion patterns of the gastric pouch during laparoscopic Roux-en-Y gastric bypass (LRYGB) using the VLS technique.

METHODS: Twenty patients were enrolled. Tissue oxygenation (StO2%) measurements were performed at three different localizations of the gastric wall, prior and after the creation of the gastric pouch, and after the creation of the gastro-jejunostomy.

RESULTS: Prior to the creation of the gastric pouch, the lowest StO2% levels were observed at the level of the distal esophagus with a median StO2% of 43 (IQR 40.8-49.5). After the creation of the gastric pouch and after the creation of the gastro-jejunostomy, the lowest StO2% levels were recorded at the level of the His angle with median values of 29% (IQR 20-38.5) and 34.5% (IQR 19-39), respectively. The highest mean StO2 reduction was recorded at the level of the His angle after the creation of the gastric pouch, and it was 18.3% (SD ± 18.1%, p < 0.001). A reduction of StO2% was recorded at all localizations after the formation of the gastro-jejunostomy compared to the beginning of the operation, but the mean differences of the StO2% levels were statistically significant only at the resection line of the pouch and at the His angle (p = 0.044 and p < 0.001, respectively).

CONCLUSION: Gastric pouch demonstrates reduction of StO2% during LRYGB. VLS is a useful technique to assess microperfusion patterns of the stomach during LRYGB.

PMID:36243899 | DOI:10.1007/s11695-022-06318-z

Ophthalmol Ther. 2022 Oct 15. doi: 10.1007/s40123-022-00586-9. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to compare modified knotless transscleral suture fixation of intraocular lens (IOL) with traditional transscleral suture fixation for adolescents and young patients with congenital ectopia lentis (CEL).

METHODS: This retrospective cohort study included 49 patients with CEL (60 eyes) who underwent surgery at the Zhongshan Ophthalmic Center. Improvements based on knotless Z-suture fixation technique were made to form a modified knotless method, in which thicker 8-0 polypropylene sutures were used, and double parallel scleral grooves were constructed behind the limbus instead of triangular lamellar scleral flaps to cover suture stitches. Modified knotless transscleral fixation of IOL was conducted on 30 eyes, and the other 30 eyes underwent traditional transscleral fixation surgery. Pre- and postoperative best-corrected visual acuity (BCVA), refractive error, astigmatism, other ocular parameters, and complications were statistically analyzed.

RESULTS: For patients in the modified knotless group, the mean cylindrical refractive error and astigmatism at 1 month and 3 months postoperative were lower (all P < 0.05), and the mean IOL tilt degree was smaller at 3 months postoperative (3.21° ± 2.13° vs. 5.65° ± 3.66°, P = 0.032). The incidence of suture exposure in the modified knotless group was also lower than in the controls (0 vs. 16.7%, P = 0.026). No group differences were observed in mean BCVA, spherical equivalent, or other ocular biometric parameters between groups.

CONCLUSION: Modified knotless technique was a valid method to achieve optimal IOL position and reduce postoperative astigmatism for adolescents and young patients with CEL. It effectively reduced the incidence of knot-related complications, greatly improved the postoperative comfort, and achieved aesthetic benefits.

PMID:36243894 | DOI:10.1007/s40123-022-00586-9

Pharmacogenomics J. 2022 Oct 15. doi: 10.1038/s41397-022-00290-8. Online ahead of print.

ABSTRACT

Psoriatic arthritis (PsA) is a heterogeneous chronic musculoskeletal disease, affecting up to 30% of people with psoriasis. Research into PsA pathogenesis has led to the development of targeted therapies, including Tumor Necrosis Factor inhibitors (TNF-i). Good response is only achieved by ~60% of patients leading to ‘trial and error’ drug management approaches, adverse reactions and increasing healthcare costs. Robust and well-validated biomarker identification, and subsequent development of sensitive and specific assays, would facilitate the implementation of a stratified approach into clinical care. This review will summarise potential genetic biomarkers for TNF-i (adalimumab, etanercept and infliximab) response that have been reported to date. It will also comment upon the importance of managing clinical confounders when understanding drug response prediction. Variants in multiple gene regions including TNF-A, FCGR2A, TNFAIP3, TNFR1/TNFR1A/TNFRSF1A, TRAIL-R1/TNFRSF10A, FCGR3A have been reported to correlate with TNF-i response at various levels of statistical significance in patients with PsA. However, results were often from heterogenous and underpowered cohorts and none are currently implemented into clinical practice. External validation of genetic biomarkers in large, well-documented cohorts is required, and assessment of the predictive value of combining multiple genetic biomarkers with clinical measures is essential to clinically embed pharmacogenomics into PsA drug management.

PMID:36243888 | DOI:10.1038/s41397-022-00290-8

Sci Rep. 2022 Oct 15;12(1):17327. doi: 10.1038/s41598-022-22243-8.

ABSTRACT

Modelling extreme values distributions, such as wave height time series where the higher waves are much less frequent than the lower ones, has been tackled from the point of view of the Peak-Over-Threshold (POT) methodologies, where modelling is based on those values higher than a threshold. This threshold is usually predefined by the user, while the rest of values are ignored. In this paper, we propose a new method to estimate the distribution of the complete time series, including both extreme and regular values. This methodology assumes that extreme values time series can be modelled by a normal distribution in a combination of a uniform one. The resulting theoretical distribution is then used to fix the threshold for the POT methodology. The methodology is tested in nine real-world time series collected in the Gulf of Alaska, Puerto Rico and Gibraltar (Spain), which are provided by the National Data Buoy Center (USA) and Puertos del Estado (Spain). By using the Kolmogorov-Smirnov statistical test, the results confirm that the time series can be modelled with this type of mixed distribution. Based on this, the return values and the confidence intervals for wave height in different periods of time are also calculated.

PMID:36243880 | DOI:10.1038/s41598-022-22243-8

Sci Rep. 2022 Oct 15;12(1):17303. doi: 10.1038/s41598-022-21458-z.

ABSTRACT

Hypertension represents the main risk factor for the onset of cardiovascular diseases. Pharmacological treatments to control hypertension have been associated with new treatments involving physical activity and/or the intake of natural components (nutraceuticals). We here report the effects produced by a combination of a natural component (catechins) and a moderate exercise program on the development of hypertension in spontaneous hypertensive rats compared with those of each individual treatment. Arterial blood pressure and heart rate were measured with a non-invasive method in 28 rats randomly assigned to four groups: rats subjected to moderate physical exercise; rats with a catechins-enriched diet; rats subjected to moderate physical exercise combined with a catechins-enriched diet; control, untreated-rats left to age. All treatments were applied for 6 weeks. The statistical analysis revealed that the three treatments significantly reduced the weekly increase in arterial blood pressure observed in control rats (SBP, P < 0.0001; DBP, P = 0.005). However, the reduction of arterial blood pressure induced by combined treatments was not higher than that induced by the single treatment, but more prolonged. All treatments showed strong antioxidative properties. Our data show that physical activity and a diet enriched with catechins individually have an important hypotensive effect, while the association did not produce a higher hypotensive effect than the single treatment, even if it was able to decrease blood pressure for a longer time. These findings have important implications for developing a protocol to apply in novel hypertension prevention procedures.

PMID:36243879 | DOI:10.1038/s41598-022-21458-z

Sci Data. 2022 Oct 15;9(1):628. doi: 10.1038/s41597-022-01732-5.

ABSTRACT

We present an integrated database suitable for the investigation of the economic development of countries by using the Economic Fitness and Complexity framework. Firstly, we implement machine learning techniques to reconstruct the export flow of services and we combine them to the export flow of the physical goods, generating a complete view of the international market, denoted the Integrated database. Successively, we support the technical quality of the database by computing the main metrics of the Economic Fitness and Complexity framework: (i) we build a statistically validated network of economic activities, where preferred paths of development and clusters of High-Tech industries naturally emerge; (ii) we evaluate the Economic Fitness, an algorithmic assessment of the competitiveness of countries, removing the unexpected misbehaviour of economies under-represented by the sole consideration of the export of the physical goods.

PMID:36243877 | DOI:10.1038/s41597-022-01732-5

Syst Rev. 2022 Oct 15;11(1):220. doi: 10.1186/s13643-022-02090-4.

ABSTRACT

BACKGROUND: Suboptimal blood pressure control among people living with diabetes mellitus (DM) is one of the primary causes of cardiovascular complications and death in sub-Saharan Africa (SSA). However, there is a paucity of evidence on the prevalence and associated factors of suboptimal blood pressure control in SSA. Therefore, this review aimed to estimate its pooled prevalence and associated factors among people living with DM in SSA. METHODS: We systematically searched PubMed, African Journals OnLine, HINARI, ScienceDirect, Google Scholar, and direct Google to access observational studies conducted in SSA. Microsoft Excel spreadsheet was used to extract the data, which was exported into STATA/MP version 16.0 for further analyses. Heterogeneity across studies was checked using Cochran’s Q test statistics and I² test, and small study effect was checked using Funnel plot symmetry and Egger’s statistical test at a 5% significant level. A random-effects model was used to estimate the pooled prevalence and associated factors of suboptimal blood pressure control at a 95% confidence interval (CI) and significance level of p < 0.05.

RESULTS: Of the 7329 articles retrieved, 21 articles were eligible for the meta-analysis. After performing random-effects model, the pooled prevalence of suboptimal blood pressure control was 69.8% (95% CI: 63.43, 76.25%). Poor adherence to antihypertensive treatment (OR = 1.7; 95% CI: 1.03-2.80, I² = 0.0%, p = 0.531) and overweight (OR = 2.4, 95% CI: 1.57-3.68, I² = 0.00%, p = 0.47) were significantly associated with suboptimal blood pressure control.

CONCLUSIONS: The prevalence of suboptimal blood pressure control among diabetic patients in SSA was high, and poor adherence to antihypertensive treatment and overweight were significantly associated with suboptimal blood pressure control. Hence, there is an urgent need for initiatives to improve and control hypertension, and preventive measures should concentrate on modifiable risk factors.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020187901.

PMID:36243876 | DOI:10.1186/s13643-022-02090-4