Category: Nevin Manimala

PLoS One. 2021 May 20;16(5):e0252091. doi: 10.1371/journal.pone.0252091. eCollection 2021.

ABSTRACT

In newborn screening, samples suspected for congenital adrenal hyperplasia (CAH), a potentially lethal inborn error of steroid biosynthesis, need to be confirmed using liquid chromatography-tandem mass spectrometry. Daily quality controls (QCs) for the 2nd-tier CAH assay are not commercially available and are therefore generally prepared within the laboratory. For the first time, we aimed to compare five different QC preparation approaches used in routine diagnostics for CAH on the concentrations of cortisol, 21-deoxycortisol, 11-deoxycortisol, 4-androstenedione and 17-hydroxyprogesterone in dried blood spots. The techniques from Prep1 to Prep5 were tested at two analyte concentrations by spiking aliquots of a steroid-depleted blood, derived from washed erythrocyte suspension and steroid-depleted serum. The preparation processes differed in the sequence of the preparation steps and whether freeze-thaw cycles were used to facilitate blood homogeneity. The five types of dried blood spot QCs were assayed and quantitated in duplicate on five different days using a single calibration row per day. Inter-assay variations less than 15% and concentrations within ±15% of the nominal values were considered acceptable. Results obtained by means of the four dried blood spot QC preparation techniques (Prep1, Prep2, Prep4 and Prep5) were statistically similar and remained within the ±15% ranges in terms of both reproducibility and nominal values. However, concentration results for Prep3 (spiking prior to three freeze-thaw cycles) were significantly lower than the nominal values in this setting, with differences exceeding the ±15% range in many cases despite acceptable inter-assay variations. These findings have implications for the in-house preparation of QC samples in laboratory developed tests for CAH, including 2nd-tier assays in newborn screening.

PMID:34015037 | DOI:10.1371/journal.pone.0252091

PLoS One. 2021 May 20;16(5):e0251782. doi: 10.1371/journal.pone.0251782. eCollection 2021.

ABSTRACT

BACKGROUND: Early life exposure to adverse environments, and maternal stress in particular, has been shown to increase risk for metabolic diseases and neurobehavioral disorders. While many studies have examined the hypothalamic-pituitary-adrenal axis (HPA axis) as the primary mechanism behind these relationships, emerging research on the brain-gut axis suggests that the microbiome may play a role. In this study, we tested the relationships among maternal precarity and HPA axis dysregulation during the peripartum period, infant gut microbiome composition, and infant HPA axis functioning.

METHODS: Data come from 25 mother-infant dyads in the Galápagos, Ecuador. Women completed surveys on precarity measures (food insecurity, low social support, depression, and stress) and gave salivary cortisol samples during and after pregnancy. Infant salivary cortisol and stool were collected in the postpartum. Statistical significance of differences in microbial diversity and relative abundance were assessed with respect to adjusted linear regression models.

RESULTS: Maternal precarity was associated with lower diversity and higher relative abundance of Enterobacteriaceae and Streptococcaceae and a lower relative abundance of Bifidobacterium and Lachnospiraceae. These patterns of colonization for Enterobacteriaceae and Bifidobacterium mirrored those found in infants with HPA axis dysregulation. Maternal HPA axis dysregulation during pregnancy was also associated with a greater relative abundance of Veillonella.

CONCLUSIONS: Overall, exposures to precarity and HPA axis dysregulation were associated with an increase in groups that include potentially pathogenic bacteria, including Enterobacteriaceae, Streptococcaceae, and Veillonella, and a decrease in potentially protective bacteria, including Bifidobacterium and Lachnospiraceae, as well as a decrease in overall diversity.

PMID:34015045 | DOI:10.1371/journal.pone.0251782

PLoS One. 2021 May 20;16(5):e0251934. doi: 10.1371/journal.pone.0251934. eCollection 2021.

ABSTRACT

We and others previously reported that the direct-acting agents (DAA) NS5A inhibitors (NS5Ai) and the host-targeting agents cyclophilin inhibitors (CypIs) inhibit HCV replication in vitro. In this study, we investigated whether the combination of NS5Ai and CypI offers a potent anti-HCV effect in vivo. A single administration of NS5Ai or CypI alone to HCV-infected humanized-mice inhibits HCV replication. The combination of NS5Ai with CypI suppresses HCV (GT1a, GT2a, GT3a and GT4a) replication in an additive manner. NS5Ai/CypI combinations provide a statistically more profound anti-HCV inhibition for GT2a and GT3a than GT1a and GT4a, leading to a fastest and deepest inhibition of GT2a and GT3a replications. Combining CypI with NS5Ai prevents the viral rebound normally observed in mice treated with NS5Ai alone. Results were confirmed in mice implanted with human hepatocytes from different donors. Therefore, the combination of NS5Ai with CypI may serve as a regimen for the treatment of HCV patients with specific genotypes and disorder conditions, which diminish sustain viral response levels to DAA, such as GT3a infection, cirrhosis, and DAA resistance associated with the selection of resistance-associated substitutions present at baseline or are acquired during treatment.

PMID:34014993 | DOI:10.1371/journal.pone.0251934

PLoS One. 2021 May 20;16(5):e0251476. doi: 10.1371/journal.pone.0251476. eCollection 2021.

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a common postoperative complication with an incidence of nearly 15%. Relatively balanced fluid management, flexible use of vasoactive drugs, multimodal analgesia containing non-steroidal anti-inflammatory drugs are fundamental to ERAS protocols. However, these basic tenants may lead to an increased incidence of postoperative AKI.

METHODS: A search was done in the PubMed, Embase, Cochrane Library and reference lists to identify relevant studies from inception until May 2020 to be included in this study. Effects were summarized using pooled risk ratios (RRs), mean differences (MDs) and corresponding 95% confidence intervals (Cls) with random effect model. Heterogeneity assessment, sensitivity analysis, and publication bias were performed.

RESULTS: A systematic review of nineteen cohort studies covering 17,205 patients, comparing impact of ERAS with conventional care on postoperative AKI was performed. Notably, the ERAS regimen did not increase the incidence of postoperative AKI compared with standard care (RR: 1.21; 95% CI: 0.96 to 1.52; I2 = 53%). Both goal-directed fluid therapy (RR: 1.26; 95% CI: 0.99-1.61; I2 = 55%) and restrictive fluid management (RR: 1.06; 95% CI: 0.57-1.98; I2 = 60%) had no significant effect on the incidence of postoperative AKI. There was no significant statistical difference between different AKI diagnostic criteria (P = 0.43; I2 = 0%). ERAS group had significantly shorter hospital stay (MD: -1.54; 95% CI: -1.91 to -1.17; I2 = 66%). There was no statistical difference in 30-day readmission rate (RR: 0.98; 95% CI: 0.80 to 1.20; I2 = 42%), 30-day reoperation rate (RR: 0.98; 95% CI: 0.71 to 1.34; I2 = 42%) and mortality (RR: 0.81; 95% CI: 0.59 to 1.11; I2 = 0%) between the two groups.

CONCLUSIONS: This meta-analysis suggests that ERAS protocols do not increase readmission or reoperation rates and mortality while significantly reducing LOS. Most importantly, the ERAS protocol was shown to have no promoting effect on the incidence of postoperative AKI. Even GDFT and restrictive fluid management cannot avoid the occurrence of postoperative AKI, and the ERAS protocol is still worth recommending and its safety is further confirmed.

PMID:34015002 | DOI:10.1371/journal.pone.0251476

PLoS One. 2021 May 20;16(5):e0251935. doi: 10.1371/journal.pone.0251935. eCollection 2021.

ABSTRACT

BACKGROUND: Multiple psychological factors of suicidal behaviour have been identified so far; however, little is known about state-dependent alterations and the interplay of the most prominent components in a suicidal crisis. Thus, the combined effect of particular personality characteristics and decision-making performance was observed within individuals who recently attempted suicide during a major depressive episode.

METHODS: Fifty-nine medication-free major depressed patients with a recent suicide attempt (within 72 h) and forty-five healthy control individuals were enrolled in this cross-sectional study. Temperament and character factors, impulsivity and decision-making performance were assessed. Statistical analyses aimed to explore between-group differences and the most powerful contributors to suicidal behaviour during a depressive episode.

RESULTS: Decision-making and personality differences (i.e. impulsivity, harm avoidance, self-directedness, cooperativeness and transcendence) were observed between the patient and the control group. Among these variables, decision-making, harm avoidance and self-directedness were shown to have the strongest impact on a recent suicide attempt of individuals with a diagnosis of major depressive disorder according to the results of the binary logistic regression analysis. The model was significant, adequately fitted the data and correctly classified 79.8% of the cases.

CONCLUSIONS: The relevance of deficient decision-making, high harm avoidance and low self-directedness was modelled in the case of major depressed participants with a recent suicide attempt; meaning that these individuals can be described with the myopia for future consequences, a pessimistic, anxious temperament; and a character component resulting in the experience of aimlessness and helplessness. Further studies that use a within-subject design should identify and confirm additional characteristics specific to the suicidal mind.

PMID:34015015 | DOI:10.1371/journal.pone.0251935

PLoS One. 2021 May 20;16(5):e0251742. doi: 10.1371/journal.pone.0251742. eCollection 2021.

ABSTRACT

BACKGROUND: This study provides detailed characteristics of vector populations in preparation for a three-arm cluster randomized controlled trial (RCT) aiming to compare the community impact of dual active-ingredient (AI) long-lasting insecticidal nets (LLINs) that combine two novel insecticide classes-chlorfenapyr or pyriproxifen-with alpha-cypermethrin to improve the prevention of malaria transmitted by insecticide-resistant vectors compared to standard pyrethroid LLINs.

METHODS: The study was carried out in 60 villages across Cove, Zangnanando and Ouinhi districts, southern Benin. Mosquito collections were performed using human landing catches (HLCs). After morphological identification, a sub-sample of Anopheles gambiae s.l. were dissected for parity, analyzed by PCR for species and presence of L1014F kdr mutation and by ELISA-CSP to identify Plasmodium falciparum sporozoite infection. WHO susceptibility tube tests were performed by exposing adult An. gambiae s.l., collected as larvae from each district, to 0.05% alphacypermethrin, 0.75% permethrin, 0.1% bendiocarb and 0.25% pirimiphos-methyl. Synergist assays were also conducted with exposure first to 4% PBO followed by alpha-cypermethrin.

RESULTS: An. gambiae s.l. (n = 10807) was the main malaria vector complex found followed by Anopheles funestus s.l. (n = 397) and Anopheles nili (n = 82). An. gambiae s.l. was comprised of An. coluzzii (53.9%) and An. gambiae s.s. (46.1%), both displaying a frequency of the L1014F kdr mutation >80%. Although more than 80% of people slept under standard LLIN, human biting rate (HBR) in An. gambiae s.l. was higher indoors [26.5 bite/person/night (95% CI: 25.2-27.9)] than outdoors [18.5 b/p/n (95% CI: 17.4-19.6)], as were the trends for sporozoite rate (SR) [2.9% (95% CI: 1.7-4.8) vs 1.8% (95% CI: 0.6-3.8)] and entomological inoculation rate (EIR) [21.6 infected bites/person/month (95% CI: 20.4-22.8) vs 5.4 (95% CI: 4.8-6.0)]. Parous rate was 81.6% (95%CI: 75.4-88.4). An. gambiae s.l. was resistant to alpha-cypermethrin and permethrin but, fully susceptible to bendiocarb and pirimiphos-methyl. PBO pre-exposure followed by alpha-cypermethrin treatment induced a higher 24 hours mortality compared to alphacypermethrin alone but not exceeding 40%.

CONCLUSIONS: Despite a high usage of standard pyrethroid LLINs, the study area is characterized by intense malaria transmission. The main vectors An. coluzzii and An. gambiae s.s. were both highly resistant to pyrethroids and displayed multiple resistance mechanisms, L1014F kdr mutation and mixed function oxidases. These conditions of the study area make it an appropriate site to conduct the trial that aims to assess the effect of novel dual-AI LLINs on malaria transmitted by insecticide-resistant vectors.

PMID:34014982 | DOI:10.1371/journal.pone.0251742

PLoS One. 2021 May 20;16(5):e0251403. doi: 10.1371/journal.pone.0251403. eCollection 2021.

ABSTRACT

Dengue is a re-emerging disease, currently considered the most important mosquito-borne arbovirus infection affecting humankind, taking into account both its morbidity and mortality. Brazil is considered an endemic country for dengue, such that more than 1,544,987 confirmed cases were notified in 2019, which means an incidence rate of 735 for every 100 thousand inhabitants. Climate is an important factor in the temporal and spatial distribution of vector-borne diseases, such as dengue. Thus, rainfall and temperature are considered macro-factors determinants for dengue, since they directly influence the population density of Aedes aegypti, which is subject to seasonal fluctuations, mainly due to these variables. This study examined the incidence of dengue fever related to the climate influence by using temperature and rainfall variables data obtained from remote sensing via artificial satellites in the metropolitan region of Rio de Janeiro, Brazil. The mathematical model that best fits the data is based on an auto-regressive moving average with exogenous inputs (ARMAX). It reproduced the values of incidence rates in the study period and managed to predict with good precision in a one-year horizon. The approach described in present work may be replicated in cities around the world by the public health managers, to build auxiliary operational tools for control and prevention tasks of dengue, as well of other arbovirus diseases.

PMID:34014989 | DOI:10.1371/journal.pone.0251403

PLoS One. 2021 May 20;16(5):e0251777. doi: 10.1371/journal.pone.0251777. eCollection 2021.

ABSTRACT

BACKGROUND: Diabetes mellitus is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Diabetes and its complications can be reduced by enhancing the attitude of the community. However, there is limited information regarding attitude towards diabetes in northwest Ethiopia. Therefore, this study determined the attitude and associated factors of diabetes mellitus among adult non-diabetic participants in Gondar city.

METHODS: A community-based cross-sectional study was conducted in Gondar city. Systematic random sampling was employed to select 626 non-diabetic participants. The data were collected using a pre-tested structured questionnaire. Descriptive statistics, processing, and analysis were done using STATA version 14. Both bivariable and multivariable binary logistic regressions were used to identify the associated factors. An adjusted odds ratio with a 95% confidence interval was used to calculate a level of significance.

RESULTS: Of 626 participants, 572 (91.37%) study subjects heard about diabetes mellitus. Three hundred and fifteen participants (55.07%) (95% CI: 50.9% – 59.1%) had a favorable attitude towards diabetes mellitus. Having good knowledge about diabetes (adjusted odds ratio = 2.69, 95% CI: 1.88, 3.87), and higher educational status (adjusted odds ratio = 1.69, 95% CI: 1.04, 2.78) were positively associated with a favorable attitude towards diabetes mellitus. Female gender (adjusted odds ratio = 0.68, 95% CI: 0.47, 0.98), on the other hand, had poor attitude towards diabetes mellitus.

CONCLUSION: In this study, a favorable attitude towards diabetes was low among adult non-diabetic participants. Good knowledge, higher educational status, and being male were the factors associated with a favorable attitude towards diabetes.

PMID:34014991 | DOI:10.1371/journal.pone.0251777

PLoS One. 2021 May 20;16(5):e0239793. doi: 10.1371/journal.pone.0239793. eCollection 2021.

ABSTRACT

MOTIVATION: Local protein structure is usually described via classifying each peptide to a unique class from a set of pre-defined structures. These classifications may differ in the number of structural classes, the length of peptides, or class attribution criteria. Most methods that predict the local structure of a protein from its sequence first rely on some classification and only then proceed to the 3D conformation assessment. However, most classification methods rely on homologous proteins’ existence, unavoidably lose information by attributing a peptide to a single class or suffer from a suboptimal choice of the representative classes.

RESULTS: To alleviate the above challenges, we propose a method that constructs a peptide’s structural representation from the sequence, reflecting its similarity to several basic representative structures. For 5-mer peptides and 16 representative structures, we achieved the Q16 classification accuracy of 67.9%, which is higher than what is currently reported in the literature. Our prediction method does not utilize information about protein homologues but relies only on the amino acids’ physicochemical properties and the resolved structures’ statistics. We also show that the 3D coordinates of a peptide can be uniquely recovered from its structural coordinates, and show the required conditions under various geometric constraints.

PMID:34014953 | DOI:10.1371/journal.pone.0239793

PLoS One. 2021 May 20;16(5):e0251427. doi: 10.1371/journal.pone.0251427. eCollection 2021.

ABSTRACT

BACKGROUND: Little research has explored the influence of social context on health of Indian adolescents. We conceptualized community-level women’s education (proxy for value placed on women’s wellbeing) as exerting contextual influence on adolescent hemoglobin level and body mass index (BMI).

METHODS: We derived our sample of more than 62,000 adolescent aged 15 through 17 years from the Indian National Family Health Survey 2015-16. The sample consisted of a total of 62648 adolescents (54232 girls and 8416 boys) for the hemoglobin, and 62846 adolescents (54383 girls and 8463 boys) for the BMI analysis. We fitted multilevel random intercepts linear regression models to test the association of village- and urban-ward-level-women’s education with hemoglobin level and BMI of adolescents, accounting for their own and their mother’s education; as well as relevant covariates.

FINDINGS: Our fully adjusted model estimated that if the 52% of communities with less than 20 percent of women having a tenth-grade education in our sample were to achieve 100 percent tenth-grade completion in women, hemoglobin would be 0·2 g/dl higher (p<0·001) and BMI would be 0·62 kg/m2 higher on average among all adolescents in such communities. Unexplained variance estimates at the contextual level remained statistically significant, indicating the importance of context on adolescent undernutrition.

INTERPRETATIONS: Adolescents are deeply embedded in their context, influenced by contextual factors affecting health. Promoting adolescent health therefore implies altering social norms related to adolescent health and health behaviors; along with structural changes creating a health-promoting environment. Integrating our empirical findings with theoretically plausible pathways connecting community-level women’s education with adolescent undernutrition, we suggest that enhancing community-level women’s education beyond high school is necessary to facilitate these processes.

IMPLICATIONS: Addressing contextual determinants of adolescent undernutrition might be the missing link in India’s adolescent anemia and undernutrition prevention efforts, which are currently focused heavily on individual-level biomedical determinants of the problem.

PMID:34014954 | DOI:10.1371/journal.pone.0251427