Category: Nevin Manimala

J Insect Sci. 2022 Mar 1;22(2):9. doi: 10.1093/jisesa/ieac015.

ABSTRACT

Termites are social insects living in colonies composed of worker, soldier, and reproductive castes. Termite hindguts are inhabited by all three domains of life- Eukarya (protists), Bacteria, and Archaea. These gut microorganisms are horizontally and vertically transferred by nestmates and reproductives, respectively. Prior evidence suggests that every colony potentially has a different gut microbiome that was transferred vertically and horizontally over time. However, we do not know if different colonies reared in the laboratory on the same diet will ultimately demonstrate similar microbial composition and structure. Therefore, we looked at gut bacteria in Eastern subterranean termite (Reticulitermes flavipes) colonies that were reared in the laboratory with identical diets and rearing conditions. Based on16S rRNA gene sequencing, the observed features, and Shannon’s diversity were significantly different between the colonies while differences in Pielou evenness and Faith phylogenetic diversity were not statistically significant. In addition, the microbial community structures were significantly different between colonies. Based on ANCOM (Analysis of Composition of Microbiomes), the taxa Elizabethkingia (Bacteroidetes: Flavobacteriales) and Chryseobacterium (Bacteroidetes: Flavobacteriales) were differentially abundant between the colonies. These results suggest that providing the exact same diet and rearing environment for >2 yr cannot result in identical gut microbiomes between termite colonies.

PMID:35381082 | DOI:10.1093/jisesa/ieac015

Blood Adv. 2022 Apr 5:bloodadvances.2021005648. doi: 10.1182/bloodadvances.2021005648. Online ahead of print.

ABSTRACT

Inflammatory stimuli have divergent effects on peripheral platelet counts, although the mechanisms of thrombocytopenic and thrombocytotic responses remain poorly understood. A candidate gene approach targeting 326 polymorphic genes enriched in thrombopoietic and cytokine signaling pathways was applied to identify single nucleotide variants (SNVs) implicated in enhanced platelet responses in cohorts with reactive (RT) or essential (myeloproliferative neoplasm [MPN]) thrombocytosis (ET). Cytokine profiles incorporating a 15-member subset, pathway topology, and functional interactive networks were distinct between ET and RT, consistent with distinct regulatory pathways of exaggerated thrombopoiesis. Genetic studies using aggregate (ET + RT) or ET-restricted cohorts identified associations with 2 IFNA16 (interferon-α16) SNVs, and the ET associations were validated in a second independent cohort (p-value 0.0002). Odds Ratio (OR) of the combined ET cohort (N = 105) was 4.92, restricted to the JAK2V617F-negative subset (OR 5.01). ET sub-stratification analysis by variant IFNA16 demonstrated statistically significant increase in interferon-α16 levels (p = 0.002) among 16 quantifiable cytokines. Recombinantly-expressed variant IFN-α16 encompassing 3 linked non-synonymous SNVs (E65 H95 P133) retained comparable antiviral (AV) and pSTAT signaling profiles as native IFN-α16 (V65 D95 A133) or IFN-α2, although both native and variant IFN-α16 demonstrated stage-restricted differences (compared to IFN-α2) of interferon-regulated genes in CD34+-stimulated megakaryocytes. These data implicate IFNA16 (IFN-α16 gene product) as a putative susceptibility locus (driver) within the broader disrupted cytokine network evident in MPNs, and provide a framework for dissecting functional interactive networks regulating stress or MPN thrombopoiesis.

PMID:35381074 | DOI:10.1182/bloodadvances.2021005648

Br J Surg. 2022 Apr 6:znac086. doi: 10.1093/bjs/znac086. Online ahead of print.

ABSTRACT

BACKGROUND: Non-operative management of uncomplicated acute appendicitis is an option, but omission of antibiotics from the regimen has not been tested.

METHODS: A double-blind, placebo-controlled, superiority RCT in adults with CT-confirmed uncomplicated acute appendicitis was designed to compare placebo with antibiotics (intravenous ertapenem followed by oral levofloxacin and metronidazole). The primary endpoint was treatment success (resolution resulting in discharge without appendicectomy within 10 days); secondary outcomes included pain scores, complications, hospital stay, and return to work.

RESULTS: From May 2017 to September 2020, 72 patients with a mean(s.d.) age of 37.5 (11.1) years were recruited at five hospitals. Six were excluded after randomization (5 early consent withdrawals, 1 randomization protocol violation), 35 were assigned to receive antibiotics, and 31 to receive placebo. Enrolment challenges (including hospital pharmacy resources in an acute-care surgery setting) meant that only the lowest sample size of three predefined scenarios was achieved. The 10-day treatment success rate was 87 (95 per cent c.i. 75 to 99) per cent for placebo and 97 (92 to 100) per cent for antibiotics. This clinical difference of 10 (90 per cent c.i. -0.9 to 21) per cent was not statistically different for the primary outcome (1-sided P = 0.142), and secondary outcomes were similar.

CONCLUSION: The lack of antibiotic superiority statistically suggests that a non-inferiority trial against placebo is warranted in adults with CT-confirmed mild appendicitis. Registration number: EudraCT 2015-003634-26 (https://eudract.ema.europa.eu/eudract-web/index.faces), NCT03234296 (http://www.clinicaltrials.gov).

PMID:35381080 | DOI:10.1093/bjs/znac086

JAMA. 2022 Apr 5. doi: 10.1001/jama.2022.4315. Online ahead of print.

ABSTRACT

IMPORTANCE: Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen and dosage.

OBJECTIVE: To compare efficacy and adverse effects of the 3 most frequently prescribed corticosteroid regimens in boys with Duchenne muscular dystrophy.

DESIGN, SETTING, AND PARTICIPANTS: Double-blind, parallel-group randomized clinical trial including 196 boys aged 4 to 7 years with Duchenne muscular dystrophy who had not previously been treated with corticosteroids; enrollment occurred between January 30, 2013, and September 17, 2016, at 32 clinic sites in 5 countries. The boys were assessed for 3 years (last participant visit on October 16, 2019).

INTERVENTIONS: Participants were randomized to daily prednisone (0.75 mg/kg) (n = 65), daily deflazacort (0.90 mg/kg) (n = 65), or intermittent prednisone (0.75 mg/kg for 10 days on and then 10 days off) (n = 66).

MAIN OUTCOMES AND MEASURES: The global primary outcome comprised 3 end points: rise from the floor velocity (in rise/seconds), forced vital capacity (in liters), and participant or parent global satisfaction with treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM; score range, 0 to 100), each averaged across all study visits after baseline. Pairwise group comparisons used a Bonferroni-adjusted significance level of .017.

RESULTS: Among the 196 boys randomized (mean age, 5.8 years [SD, 1.0 years]), 164 (84%) completed the trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P < .001 for daily prednisone vs intermittent prednisone using a global test; P = .017 for daily deflazacort vs intermittent prednisone using a global test) and the daily regimens did not differ significantly (P = .38 for daily prednisone vs daily deflazacort using a global test). The between-group differences were principally attributable to rise from the floor velocity (0.06 rise/s [98.3% CI, 0.03 to 0.08 rise/s] for daily prednisone vs intermittent prednisone [P = .003]; 0.06 rise/s [98.3% CI, 0.03 to 0.09 rise/s] for daily deflazacort vs intermittent prednisone [P = .017]; and -0.004 rise/s [98.3% CI, -0.03 to 0.02 rise/s] for daily prednisone vs daily deflazacort [P = .75]). The pairwise comparisons for forced vital capacity and TSQM global satisfaction subscale score were not statistically significant. The most common adverse events were abnormal behavior (22 [34%] in the daily prednisone group, 25 [38%] in the daily deflazacort group, and 24 [36%] in the intermittent prednisone group), upper respiratory tract infection (24 [37%], 19 [29%], and 24 [36%], respectively), and vomiting (19 [29%], 17 [26%], and 15 [23%]).

CONCLUSIONS AND RELEVANCE: Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment; there was no significant difference between the 2 daily corticosteroid regimens. The findings support the use of a daily corticosteroid regimen over the intermittent prednisone regimen tested in this study as initial treatment for boys with Duchenne muscular dystrophy.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01603407.

PMID:35381069 | DOI:10.1001/jama.2022.4315

Clin Cancer Res. 2022 Apr 5:clincanres.3375.2021. doi: 10.1158/1078-0432.CCR-21-3375. Online ahead of print.

ABSTRACT

Background The current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) patients is cisplatin-based induction (IC) or adjuvant (AC) chemotherapy plus concurrent chemoradiotherapy (CRT). However, data on the optimal platinum doses for each phase of combined regimens are lacking. Patients and Methods 742 NPC patients in the NPC-0501 Trial treated with CRT plus IC/AC and irradiated with intensity-modulated radiotherapy (IMRT) were analyzed. The optimal platinum dose to achieve the best overall survival (OS) in the concurrent and induction/adjuvant phases were studied. Results Evaluation of the whole series shows the optimal platinum dose was 160 mg/m2 in the concurrent and 260 mg/m2 in the induction/adjuvant phase. Repeating the analyses on 591 patients treated with cisplatin throughout (no replacement by carboplatin) confirmed the same results. The cohort with optimal platinum doses in both phases had better OS than the cohort suboptimal in both phases (Stage III: 90% vs 75%, Stage IVA-B: 80% vs 56%, at 5-year). Multivariable analyses confirmed optimal platinum doses in both phases vs. suboptimal dose in each phase are significant independent factors for OS, with hazard ratio of 0.61 (95% confidence interval [CI]=0.41-0.91) and 0.67 (95% CI=0.48-0.94), respectively. Treatment sequence was statistically insignificant after adjusting for platinum doses. Conclusion Both concurrent and IC/AC are needed for locoregionally advanced NPC, even for patients irradiated by IMRT; the concurrent platinum dosage could be set at {greater than or equal to}160 mg/m2 when coupled with adequate induction/adjuvant dosage at {greater than or equal to}260 mg/m2 (or at least {greater than or equal to}240 mg/m2). To achieve these optimal dosages, IC-CRT at conventional fractionation is favored.

PMID:35381064 | DOI:10.1158/1078-0432.CCR-21-3375

PLoS One. 2022 Apr 5;17(4):e0266082. doi: 10.1371/journal.pone.0266082. eCollection 2022.

ABSTRACT

BACKGROUND: Our objective was to assess differences in TB treatment outcomes between individuals who were HIV negative, HIV positive on anti-retroviral treatment (ART) and HIV positive not on ART, at TB treatment initiation at a rural district hospital in Eastern Cape, South Africa.

METHODS: This was a retrospective cohort study of individuals diagnosed with TB between January 2017 and April 2020 at a district hospital. Adults 15 years and over with reported HIV status and treatment outcome were included (N = 711). A categorical outcome with three levels was considered: unfavorable, down referral, and success. We report descriptive statistics for the association between HIV and ART status and treatment outcome using Chi-square and Fisher’s exact tests. A multinomial baseline logit model was used to estimate odds ratios for treatment outcomes.

RESULTS: Overall, 59% of included patients were HIV positive with 75% on ART. Eighty-eight patients 12% had an unfavorable outcome. Half of all patients were down referred with an additional 37% having a successful outcome. Individuals without HIV were more likely to be down referred (versus unfavorable) compared to individuals with untreated HIV (2.90 OR, 1.36, 6.17 95% CI). There was a greater likelihood for individuals without HIV having a successful TB treatment outcome compared to individuals with untreated HIV (4.98 OR, 2.07, 11.25 95% CI).

CONCLUSION: The majority of individuals had positive TB treatment outcomes (down referred or success). However, people without HIV had nearly five times greater odds of having successful outcomes than those with untreated HIV.

PMID:35381042 | DOI:10.1371/journal.pone.0266082

PLoS One. 2022 Apr 5;17(4):e0266533. doi: 10.1371/journal.pone.0266533. eCollection 2022.

ABSTRACT

Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne’s disease in animals with zoonotic potential; it has been linked to many chronic diseases in humans, especially gastrointestinal diseases (GID). MAP has been extensively studied in Europe and America, but little reports were published from Africa. Sudan is a unique country with close contact between humans and livestock. Despite such interaction, the one health concept is neglected in dealing with cases of humans with GID. In this study, patients admitted to the reference GID hospital in the Sudan over a period of 8 months were screened for presence of MAP in their faeces or colonic biopsies. A total of 86 patients were recruited for this study, but only 67 were screened for MAP, as 19 did not provide the necessary samples for analysis. Both real-time PCR and culture were used to detect MAP in the collected samples and the microbial diversity in patients´ faecal samples was investigated using 16S rDNA nanopore sequencing. In total, 27 (40.3%) patients were MAP positive: they were 15 males and 12 females, of ages between 21 and 80 years. Logistic regression analysis revealed no statistical significance for all tested variables in MAP positive patients (occupation, gender, contact with animal, milk consumption, chronic disease, etc.). A unique microbiome profile of MAP-positive patients in comparison to MAP-negative was found. These findings suggest that a considerable proportion of the population could be MAP infected or carriers. Therefore, increase awareness at community level is urgently needed to decrease the risk of MAP at human/animal interface. This study represents the first report of MAP in humans in the Sudan; nevertheless, a better view of the situation of MAP in humans in the country requires a larger study including patients with other conditions.

PMID:35381037 | DOI:10.1371/journal.pone.0266533

PLoS One. 2022 Apr 5;17(4):e0266484. doi: 10.1371/journal.pone.0266484. eCollection 2022.

ABSTRACT

Mapping population distribution at a fine spatial scale is essential for urban studies and planning. Numerous studies, mainly supported by geospatial and statistical methods, have focused primarily on predicting population counts. However, estimating their socio-economic characteristics beyond population counts, such as average age, income, and gender ratio, remains unattended. We enhance traditional population estimation by predicting not only the number of residents in an area, but also their demographic characteristics: average age and the proportion of seniors. By implementing and comparing different machine learning techniques (Random Forest, Support Vector Machines, and Linear Regression) in administrative areas in Singapore, we investigate the use of point of interest (POI) and real estate data for this purpose. The developed regression model predicts the average age of residents in a neighbourhood with a mean error of about 1.5 years (the range of average resident age across Singaporean districts spans approx. 14 years). The results reveal that age patterns of residents can be predicted using real estate information rather than with amenities, which is in contrast to estimating population counts. Another contribution of our work in population estimation is the use of previously unexploited POI and real estate datasets for it, such as property transactions, year of construction, and flat types (number of rooms). Advancing the domain of population estimation, this study reveals the prospects of a small set of detailed and strong predictors that might have the potential of estimating other demographic characteristics such as income.

PMID:35381028 | DOI:10.1371/journal.pone.0266484

PLoS One. 2022 Apr 5;17(4):e0266245. doi: 10.1371/journal.pone.0266245. eCollection 2022.

ABSTRACT

BACKGROUND: Colchicine has been used an effective anti-inflammatory drug to treat gout diseases. Owing to its pharmacodynamic of inhibiting interleukins, it has been repurposed to target the cytokine storm post-SARS-CoV-2 invasion. The goal of this meta-analysis was to evaluate the safety profile of colchicine in COVID-19 patients using the gold-standard randomised-control trials.

METHODS: Electronic databases (Pubmed, Google Scholar, and Cochrane) were systematically searched until June 2021 and RCTs were extracted. Outcomes of interest included all-cause mortality, COVID-19 severity, mechanical ventilation, C-reactive protein and D-dimer levels. Using a random-effects model, dichotomous outcomes were pooled using odds ratios (OR) through the generic inverse variance formula while weighted mean differences were calculated using the Wan’s method. P-values < 0.05 were considered statistically significant for all outcomes.

RESULTS: A total population of 16,048 from five RCTs were included in the analysis. Of this, 7957 were randomized to colchicine, and 8091 received standard care, with an average age of 60.67 years. Colchicine was observed to significantly reduce COVID-19 severity (OR: 0.41, 95% CI [0.22, 0.76]; p = 0.005), and CRP levels (WMD: -19.99, 95% CI [-32.09, -7.89]; p = 0.001). However, there was no significant difference in D-dimer levels (WMD: 0.31, 95% CI [-0.61, 1.23]; p = 0.51), mechanical ventilation (OR: 0.42, 95% CI [0.17, 1.03]; p = 0.06; I2 = 74%) and all-cause mortality (OR: 0.98, 95% CI [0.83, 1.16]; p = 0.84) among patients receiving colchicine or standard care.

CONCLUSION: Colchicine treatment decreased CRP levels and COVID-19 severity, with dimer levels, all-cause mortality and mechanical ventilation remaining seemingly unaffected. Thus, clinical trials need to be carried out that allow effective evaluation of colchicine in COVID-19 patients.

PMID:35381033 | DOI:10.1371/journal.pone.0266245

PLoS One. 2022 Apr 5;17(4):e0266232. doi: 10.1371/journal.pone.0266232. eCollection 2022.

ABSTRACT

BACKGROUND: As of July 2021, there has been more than 185 million documented cases of the novel coronavirus (SARS-CoV-2) infections and more than 4 million deaths globally. Despite more than 90% of documented cases being classified as “recovered” from SARS-CoV-2 infection, a proportion of patients reported a wide variety of persisting symptoms after the initial onset or acute phase of the infection, often referred to as “Long Covid”. As data on the symptomatology of post-acute SARS-CoV-2 infection gradually becomes available, there is an urgent need to organise and synthesise the data in order to define what constitutes Long Covid and assist with its management in clinical and community settings.

METHODS: This protocol follows the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines. A comprehensive literature search strategy will be developed in accordance with the Cochrane highly sensitive search guidelines. The following electronic databases will be searched for studies to include in the systematic review and meta-analysis: MEDLINE (via PubMed), Scopus, Google Scholar, Web of Science (Web of Knowledge), Science direct, EMBASE, Mednar, Psych INFO, and EBSCOhost. Dual screening will be applied at every screening stage. Two reviewers will independently screen titles, abstracts and full text of potentially eligible studies following the predefined inclusion and exclusion criteria in order to select studies to include in the review. As heterogeneity is anticipated between the included studies, data will be pooled in a meta-analysis using a random effects model. A clustering analytic approach will be applied to identify symptoms groupings and assign the symptoms into clusters. R statistical software will be used for the meta-analysis. Highly heterogenous data will be synthesised narratively. The studies will be assessed, for quality using quality assessment tools appropriate for each study design. Two reviewers will independently undertake the quality of studies assessments.

DISSEMINATION PLANS: Findings of the systematic review will be disseminated through a peer-reviewed publication and presentation of findings at conferences, workshops and government and private sector stakeholder engagement meetings.

CLINICAL TRIAL REGISTRATION: PROSPERO registration number: CRD4202126589. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD4202126589.

PMID:35381027 | DOI:10.1371/journal.pone.0266232