Nevin Manimala

mSphere. 2022 Jan 5:e0073021. doi: 10.1128/msphere.00730-21. Online ahead of print.

ABSTRACT

While differences in human virulence have been reported across nontyphoidal Salmonella (NTS) serovars and associated subtypes, a rational and scalable approach to identify Salmonella subtypes with differential ability to cause human diseases is not available. Here, we used NTS serovar Saintpaul (S. Saintpaul) as a model to determine if metadata and associated whole-genome sequence (WGS) data in the NCBI Pathogen Detection (PD) database can be used to identify (i) subtypes with differential likelihoods of causing human diseases and (ii) genes and single nucleotide polymorphisms (SNPs) potentially responsible for such differences. S. Saintpaul SNP clusters (n = 211) were assigned different epidemiology types (epi-types) based on statistically significant over- or underrepresentation of human clinical isolates, including human associated (HA; n = 29), non-human associated (NHA; n = 23), and other (n = 159). Comparative genomic analyses identified 384 and 619 genes overrepresented among isolates in 5 HA and 4 NHA SNP clusters most significantly associated with the respective isolation source. These genes included 5 HA-associated virulence genes previously reported to be present on Gifsy-1/Gifsy-2 prophages. Additionally, premature stop codons in 3 and 7 genes were overrepresented among the selected HA and NHA SNP clusters, respectively. Tissue culture experiments with strains representing 4 HA and 3 NHA SNP clusters did not reveal evidence for enhanced invasion or intracellular survival for HA strains. However, the presence of sodCI (encoding a superoxide dismutase), found in 4 HA and 1 NHA SNP clusters, was positively correlated with intracellular survival in macrophage-like cells. Post hoc analyses also suggested a possible difference in intracellular survival among S. Saintpaul lineages. IMPORTANCE Not all Salmonella isolates are equally likely to cause human disease, and Salmonella control strategies may unintentionally focus on serovars and subtypes with high prevalence in source populations but are rarely associated with human clinical illness. We describe a framework leveraging WGS data in the NCBI PD database to identify Salmonella subtypes over- and underrepresented among human clinical cases. While we identified genomic signatures associated with HA/NHA SNP clusters, tissue culture experiments failed to identify consistent phenotypic characteristics indicative of enhanced human virulence of HA strains. Our findings illustrate the challenges of defining hypo- and hypervirulent S. Saintpaul and potential limitations of phenotypic assays when evaluating human virulence, for which in vivo experiments are essential. Identification of sodCI, an HA-associated virulence gene associated with enhanced intracellular survival, however, illustrates the potential of the framework and is consistent with prior work identifying specific genomic features responsible for enhanced or reduced virulence of nontyphoidal Salmonella.

PMID:34986312 | DOI:10.1128/msphere.00730-21

J Clin Ultrasound. 2022 Jan 5. doi: 10.1002/jcu.23126. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of magnetic resonance imaging (MRI)-based comparing with computed tomography (CT)-based selection for intravenous thrombolysis in patients with acute ischemic stroke (AIS).

METHODS: Totally 462 consecutive AIS patients treated with intravenous thrombolysis within a 4.5 h window from Jan. 2016 to Dec. 2019 were enrolled. The primary endpoint was the good functional outcome defined by a modified Rankin Scale (mRS) of 0-2 at 3 months. Secondary outcomes include the excellent functional outcome defined by a mRS of 0-1 at 3 months, occurrences of symptomatic intracranial hemorrhage (SICH), 7-day mortality, and 3-month mortality.

RESULTS: Overall 172 patients received MRI and 290 received CT before they were treated with thrombolysis. The difference in the good or excellent functional outcome was not statistically significant between MRI and CT groups (both P > 0.05). The incidences of 7-day mortality (3.5% vs. 8.6%, P < 0.01), 30-day mortality (12.8% vs. 21.0%, P = 0.03), and SICH (12.2% vs. 20.3%, P < 0.01) were obviously lower for MRI-based regimen compared with CT-based regimen. Multivariate logistic regression indicated that MRI-based regimen was significantly associated with a lower risk of 7-day mortality (OR = 0.72, 95% CI: 0.53-0.91; P < 0.01), 30-day mortality (OR = 0.58, 95% CI: 0.47-0.73; P < 0.01), and SICH (OR = 0.44, 95% CI: 0.20-0.65; P < 0.01) after controlling for potential confounding factors.

CONCLUSION: Despite MRI-based thrombolysis was not demonstrated to be associated with the good functional outcome, it significantly reduced risks of mortality and SICH in patients with AIS compared with CT-based thrombolysis.

PMID:34986280 | DOI:10.1002/jcu.23126

Mil Med. 2022 Jan 5:usab543. doi: 10.1093/milmed/usab543. Online ahead of print.

ABSTRACT

INTRODUCTION: According to the Military Health System Traumatic Brain Injury (TBI) Center of Excellence, 51,261 service members suffered moderate to severe TBI in the last 21 years. Moderate to severe TBI in service members is usually related to blast injury in combat operations, which necessitates medical evacuation to higher levels of care. Prevention of secondary insult, and mitigation of the unique challenges associated with the transport of TBI patients in a combat setting are important in reducing the morbidity and mortality associated with this injury. The primary goal of this study was a secondary analysis comparing the impact of time to transport on clinical outcomes for TBI patients without polytrauma versus TBI patients with polytrauma transported out of the combat theater via Critical Care Air Transport Teams (CCATT). Our secondary objective was to describe the occurrence of in-flight events and interventions for TBI patients without polytrauma versus TBI with polytrauma to assist with mission planning for future transports.

MATERIALS AND METHODS: We performed a secondary analysis of a retrospective cohort of 438 patients with TBI who were evacuated out of theater by CCATT from January 2007 to May 2014. Polytrauma was defined as abbreviated injury scale (AIS) of at least three to another region in addition to head/neck. Time to transport was defined as the time (in days) from injury to CCATT evacuation out of combat theater. We calculated descriptive statistics and examined the associations between time to transport and preflight characteristics, in-flight interventions and events, and clinical outcomes for TBI patients with and without polytrauma.

RESULTS: We categorized patients into two groups, those who had a TBI without polytrauma (n = 179) and those with polytrauma (n = 259). Within each group, we further divided those that were transported within 1 day of injury, in 2 days, and 3 or more days. Patients with TBI without polytrauma transported in 1 or 2 days were more likely to have a penetrating injury, an open head injury, a preflight Glascow Coma Score (GCS) of 8 or lower, and be mechanically ventilated compared to those transported later. Patients without polytrauma who were evacuated in 1 or 2 days required more in-flight interventions compared to patients without polytrauma evacuated later. Patients with polytrauma who were transported in 2 days were more likely to receive blood products, and patients with polytrauma who were evacuated within 1 day were more likely to have had at least one episode of hypotension en route. Polytrauma patients who were evacuated in 2-3 days had higher hospital days compared to polytrauma with earlier evacuations. There was no significant difference in mortality between any of the groups.

CONCLUSIONS: In patients with moderate to severe TBI transported via CCATT, early evacuation was associated with a higher rate of in-flight hypotension in polytrauma patients. Furthermore, those who had TBI without polytrauma that were evacuated in 1-2 days received more in-flight supplementary oxygen, blood products, sedatives, and paralytics. Given the importance of minimizing secondary insults in patients with TBI, recognizing this in this subset of the population may help systematize ways to minimize such events. Traumatic Brain Injury patients with polytrauma may benefit from further treatment and stabilization in theater prior to CCATT evacuation.

PMID:34986265 | DOI:10.1093/milmed/usab543

Bioinformatics. 2022 Jan 5:btac004. doi: 10.1093/bioinformatics/btac004. Online ahead of print.

ABSTRACT

SUMMARY: Bayesian inference in biological modeling commonly relies on Markov chain Monte Carlo (MCMC) sampling of a multidimensional and non-Gaussian posterior distribution that is not analytically tractable. Here, we present the implementation of a practical MCMC method in the open-source software package PyBioNetFit (PyBNF), which is designed to support parameterization of mathematical models for biological systems. The new MCMC method, am, incorporates an adaptive move proposal distribution. For warm starts, sampling can be initiated at a specified location in parameter space and with a multivariate Gaussian proposal distribution defined initially by a specified covariance matrix. Multiple chains can be generated in parallel using a computer cluster. We demonstrate that am can be used to successfully solve real-world Bayesian inference problems, including forecasting of new Coronavirus Disease 2019 case detection with Bayesian quantification of forecast uncertainty.

AVAILABILITY AND IMPLEMENTATION: PyBNF version 1.1.9, the first stable release with am, is available at PyPI and can be installed using the pip package-management system on platforms that have a working installation of Python 3. PyBNF relies on libRoadRunner and BioNetGen for simulations (e.g., numerical integration of ordinary differential equations defined in SBML or BNGL files) and Dask.Distributed for task scheduling on Linux computer clusters. The Python source code can be freely downloaded/cloned from GitHub and used and modified under terms of the BSD-3 license (https://github.com/lanl/pybnf). Online documentation covering installation/usage is available (https://pybnf.readthedocs.io/en/latest/). A tutorial video is available on YouTube (https://www.youtube.com/watch?v=2aRqpqFOiS4&t=63s).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34986226 | DOI:10.1093/bioinformatics/btac004

J Pediatr Psychol. 2022 Jan 5:jsab132. doi: 10.1093/jpepsy/jsab132. Online ahead of print.

ABSTRACT

OBJECTIVE: To provide national norms and percentiles for both research and clinical scoring modalities of the Vanderbilt Attention Deficit/Hyperactivity Disorder (ADHD) Diagnostic Parent Rating Scale (VADPRS) for a representative sample of children ages 5-12 in the United States.

METHOD: The five clinical subscales of the VADPRS were completed by 1,570 caregivers of children ages 5-12 in the United States, with children representative of the national population on key demographic variables including race, sex, ethnicity, family income, and family educational level. Descriptive statistics and measures of internal consistency of both dimensional and symptom count scoring were provided for each of the five clinical subscales of the inventory, as well as percentiles and group comparisons for select dimensional scoring subscales based on age and child sex.

RESULTS: Measures of internal consistency for each subscale using both scoring modalities of the VADPRS ranged from high to acceptable. There were statistically significant differences among the different subscales for both age (ADHD hyperactivity, anxiety/depression) and sex [both presentations of ADHD, oppositional defiant disorder (ODD)] for the total sample. These differences, however, were modest in magnitude and unlikely to be clinically meaningful.

CONCLUSIONS: This study enhances the research and clinical utility of the VADPRS by providing national norms and percentiles for each of its subscales. Differences between age and sex across the sample were statistically significant for two of the subscales (Hyperactivity and Anxiety/Depression) with additional subscales significant for sex alone (Inattentive and ODD), but these differences were not substantial enough to indicate a need for separate cut-offs for screening purposes.

PMID:34986222 | DOI:10.1093/jpepsy/jsab132

Hum Reprod. 2021 Dec 27;37(1):119-128. doi: 10.1093/humrep/deab242.

ABSTRACT

STUDY QUESTION: Are transfer day, developmental stage and morphology of the competent blastocyst in pregnancies leading to live birth associated with preterm birth, birthweight, length at birth and sex of the child?

SUMMARY ANSWER: A high score in blastocyst developmental stage and in trophectoderm (TE) showed a significant association with the sex of the child, while no other associations with obstetric outcomes were observed.

WHAT IS KNOWN ALREADY: The association between blastocyst assessment scores and obstetric outcomes have been reported in small single-center studies and the results are conflicting.

STUDY DESIGN, SIZE, DURATION: Multicenter historical cohort study based on exposure data (transfer day (blastocyst developmental stage reached by Day 5 or Day 6)) blastocyst developmental stage (1-6) and morphology (TE and inner cell mass (ICM): A, B, C)) and outcome data (preterm birth, birthweight, length at birth, and sex of the child) from women undergoing single blastocyst transfer resulting in a singleton pregnancy and live birth.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 16 private and university-based facilities for clinical services and research were used. A total of 7246 women, who in 2014-2018 underwent fresh-embryo transfer with a single blastocyst or frozen-thawed embryo transfer (FET) with a single blastocyst resulting in a singleton pregnancy were identified. Linking to the Danish Medical Birth Registry resulted in a total of 4842 women with a live birth being included. Cycles with pre-implantation genetic testing and donated gametes were excluded. The analyses were adjusted for female age (n = 4842), female BMI (n = 4302), female smoking (n = 4290), parity (n = 4365), infertility diagnosis (n = 4765), type of treatment (n = 4842) and center (n = 4842); some analyses additionally included gestational age (n = 4368) and sex of the child (n = 4833).

MAIN RESULTS AND THE ROLE OF CHANCE: No statistically significant associations between blastocyst assessment scores (transfer day, developmental stage, TE, ICM) and preterm birth (8.3%) or birthweight (mean 3461.7 g) were found. The adjusted association between blastocysts with a TE score of C and a TE score of A and length at birth (mean 51.6 cm) were statistically significant (adjusted mean difference 0.4 cm (95% CI: 0.02; 0.77)). Blastocysts transferred with developmental stage score 5 compared to blastocysts transferred with score 3 had a 34% increased probability of being a boy (odds ratio (OR) 1.34 (95% CI: 1.09; 1.64). Further, TE score B blastocysts compared to TE score A blastocysts had a 31% reduced probability of being a boy (OR 0.69 (95% CI: 0.60; 0.80)).

LIMITATIONS, REASONS FOR CAUTION: It is possible that some residual confounding remains.

WIDER IMPLICATIONS OF THE FINDINGS: Blastocyst selection during ART does not appear to introduce any negative effects on obstetric outcome. Therefore, clinicians and patients can be reassured that the assessment scores of the selected blastocyst will not in themselves pose a risk of preterm birth or affect birthweight and the length at birth.

STUDY FUNDING/COMPETING INTEREST(S): Unrestricted grant from Gedeon Richter Nordics AB, Sweden. None of the authors have any competing interest to declare.

TRIAL REGISTRATION NUMBER: N/A.

PMID:34986219 | DOI:10.1093/humrep/deab242

Phys Chem Chem Phys. 2022 Jan 5. doi: 10.1039/d1cp05072a. Online ahead of print.

ABSTRACT

Nucleophilicity provides important information about the chemical reactivity of organic molecules. Experimental determination of the nucleophilicity parameter is a tedious and resource-intensive approach. Herein, we present a novel machine learning protocol that uses key structural descriptors to predict the nucleophilicities of organic molecules, which agree well with the experimental values. A data driven approach was used where quantum mechanical molecular and thermodynamic descriptors from a wide range of structurally diverse nucleophiles and relevant solvents were extracted and modelled using advanced algorithms against the experimentally available nucleophilicity values. Despite the structural diversity of nucleophiles, we are able to achieve statistically robust models with a high predictive power using tree-based and neural network algorithms trained on an in-house developed unique dataset consisting of 752 nucleophilicity values and 27 molecular descriptors.

PMID:34986215 | DOI:10.1039/d1cp05072a

PLoS One. 2022 Jan 5;17(1):e0262239. doi: 10.1371/journal.pone.0262239. eCollection 2022.

ABSTRACT

INTRODUCTION: In cholera endemic areas, the periodicity of cholera outbreaks remains unpredictable, making it difficult to organize preventive efforts. Lack of data on duration of protection conferred by oral cholera vaccines further makes it difficult to determine when to deploy preemptive vaccination. We report on the immunogenicity and waning of immunity to Shanchol™ in Lukanga Swamps.

METHODS: We enrolled a cohort of 223 participants aged between 18 and 65 years old from whom serum samples were collected at baseline, day 28 before administration of the second dose, and consecutively at 6, 12, 24, 30, 36, and 48 months. Vibriocidal antibody titres were measured and expressed as geometric mean titres. Box plots and 95% CI were computed at each visit for both Inaba and Ogawa. Seroconversion was defined as a four fold or greater increase in antibody titres compared to baseline titres.

RESULTS: Overall, seroconversion against V. cholerae Inaba and Ogawa after 1st dose was 35/134 (26%) and 34/134 (25%) respectively. We observed a statistical difference in seroconversion between the two subgroups of baseline titres (low <80 and high ≥80) for both Inaba (p = 0.02) and Ogawa (p<0.0001). From a baseline of 13.58, anti-Ogawa GMT increased to 21.95 after the first dose, but rapidly waned to 14.52, 13.13, and 12.78 at months 6, 12 and 24 respectively, and then increased to 13.21, 18.67 and 23.65 at months 30, 36 and 48 respectively. A similar trend was observed for anti-Inaba GMT across the same time points.

CONCLUSION: We found that Shanchol™ was immunogenic in our study population and that vibriocidal antibodies may not be a good marker for long-term immunity. The observed rise in titres after 36 months suggests natural exposure, and this may be a critical time window opening for natural transmission in an endemic areas. We recommend re-vaccination at this time point in high risk areas.

PMID:34986195 | DOI:10.1371/journal.pone.0262239

PLoS One. 2022 Jan 5;17(1):e0262168. doi: 10.1371/journal.pone.0262168. eCollection 2022.

ABSTRACT

Tungiasis is caused by the flea tunga penetrans and results in painful skin lesions, skin infections, and permanent disability. However, limited information is available that shows the magnitude of the problem and its risk factors that help for intervention in Ethiopia. The goal of this study was to determine the prevalence and risk factors of tungiasis in children aged 5 to 14 in Mettu woreda in 2020. A community based cross sectional study was conducted among randomly selected kebeles of Mettu woreda, in Southwest Ethiopia. To select study participants, multistage sampling was used. The data were collected through physical examination of the children, interview of parents/guardians of the children, and observation of the home environment using checklists and questionnaires. The descriptive analysis was done for socio-demographic characteristics, prevalence of tungiasis, and housing conditions. A logistic regression analysis was performed, and variables in multivariable regression reported odds ratios and their 95% confidence intervals once the variables were identified using a p-value of 0.05 as a risk factor of statistical significance. The prevalence of tungiasis among children 5-14 years of age in Mettu rural woreda was 52 percent (n = 821). As a risk factor, large family size (AOR: 2.9, 95% CI: 2.13, 4.40); school attendance (AOR: 1.5, 95% CI: 1.02, 2.18), floor inside the house (AOR: 3.8, 95% CI: 1.76, 8.43); having sleeping bed (AOR: 0.16, 95% CI: 0.03, 0.82); access to protected water sources (AOR: 0.24, 95% CI: 0.15, 0.39); access to improved toilet facilities(AOR: 0.63: 95% CI: 0.44, 0.89); access to electric services (AOR: 0.30, 95% CI: 0.15, 0.62); and lack of own farmland (AOR: 0.36, 95% CI: 0.26, 0.50) were found. Therefore, planning and implementation of interventions focus on those risk factors that are particularly important. Water, sanitation and hygiene interventions, and livelihood improvement interventions are required to solve the problem in the setting.

PMID:34986188 | DOI:10.1371/journal.pone.0262168

PLoS One. 2022 Jan 5;17(1):e0262137. doi: 10.1371/journal.pone.0262137. eCollection 2022.

ABSTRACT

The main aim of the study was to investigate the role and importance of perceived risk in medical tourism (MT). The research demonstrates that the country of origin and an assessment of the respondents’ own health condition significantly moderates the impact of their attitudes on behavioral intention. The research shows a strong correlation between the risk perceived by the respondents and their attitudes towards MT services. This relationship is significantly moderated by risk awareness, aversion to risk and gender. Additionally, an important factor in the model is the level of satisfaction with medical services in their own country. The survey using a fully structured questionnaire was conducted among young consumers from Jordan, Poland and Turkey. To verify the hypotheses, a multiple regression model with interactions was used.

PMID:34986182 | DOI:10.1371/journal.pone.0262137