Nevin Manimala

PLoS One. 2023 Jan 24;18(1):e0280827. doi: 10.1371/journal.pone.0280827. eCollection 2023.

ABSTRACT

In large areas of the ocean, iron concentrations are insufficient to promote phytoplankton growth. Numerous studies have been conducted to characterize the effect of iron on algae and how algae cope with fluctuating iron concentrations. Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. Nine transcripts were iron-responsive, with an immediate response to the addition of iron. The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. Four iron-responsive transcripts showed statistically significant differences in their decay rates between the iron-recovery samples and the actD treatment. These differences suggest regulatory mechanisms influencing gene transcription and mRNA stability. Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations.

PMID:36693065 | DOI:10.1371/journal.pone.0280827

PLoS One. 2023 Jan 24;18(1):e0279779. doi: 10.1371/journal.pone.0279779. eCollection 2023.

ABSTRACT

BACKGROUND: Despite the worldwide campaigns of COVID-19 vaccinations, the pandemic is still a major medical and social problem. The Ortho VITROS SARS-CoV-2 spike-specific quantitative IgG (VITROS S-IgG) assay has been developed to assess neutralizing antibody (NT antibody) against SARS-CoV-2 spike (S) antibodies. However, it has not been evaluated in Japan, where the total cases and death toll are lower than the rest of the world.

METHODS: The clinical performance of VITROS S-IgG was evaluated by comparing with the NT antibody levels measured by the surrogate virus neutralizing antibody test (sVNT). A total of 332 serum samples from 188 individuals were used. Of these, 219 samples were from 75 COVID-19 patients: 96 samples from 20 severe/critical cases (Group S), and 123 samples from 55 mild/moderate cases (Group M). The remaining 113 samples were from 113 healthcare workers who had received 2 doses of the BNT162b2 vaccine.

RESULTS: VITROS S-IgG showed good correlation with the cPass sVNT assay (Spearman rho = 0.91). Both VITROS S-IgG and cPass sVNT showed significantly higher plateau levels of antibodies in Group S compared to Group M. Regarding the humoral immune responses after BNT162b2 vaccination, individuals who were negative for SARS-CoV-2 nucleocapsid (N)-specific antibodies had statistically lower titers of both S-IgG and sVNT compared to individuals with a history of COVID-19 and individuals who were positive for N-specific antibodies without history of COVID-19. In individuals who were positive for N-specific antibodies, S-IgG and sVNT titers were similar to individuals with a history of COVID-19.

CONCLUSIONS: Although the automated quantitative immunoassay VITROS S-IgG showed a reasonable correlation with sVNT antibodies, there is some discrepancy between Vitros S-IgG and cPass sVNT in milder cases. Thus, VITROS S-IgG can be a useful diagnostic tool in assessing the immune responses to vaccination and herd immunity. However, careful analysis is necessary to interpret the results.

PMID:36693058 | DOI:10.1371/journal.pone.0279779

PLoS One. 2023 Jan 24;18(1):e0280957. doi: 10.1371/journal.pone.0280957. eCollection 2023.

ABSTRACT

PURPOSE: To determine the amounts of time spent in physical activity (PA), sedentary behaviour (SB), and sleep in the Thai population, as well as their sociodemographic correlates and changes over time.

METHODS: We analysed cross-sectional data collected in a population-representative, stratified random sample of 135,824 Thais aged 10 years and over as part of the two most recent Thai National time-use surveys (2009 and 2015). Daily activities reported by the participants were coded using the International Classification of Activities for Time-Use Statistics (ICATUS) and categorised as PA, SB, or sleep.

RESULTS: In the latest survey, participants spent on average the largest amount of time sleeping (geometric mean [g] = 9.44 h/day; 95% confidence interval [CI]: 9.42, 9.47), followed by PA (g = 8.60 h/day; 95% CI: 8.55, 8.64) and SB (g = 5.96 h/day; 95% CI: 5.93, 6.00). The time spent in PA was higher on weekdays, while the amounts of SB and sleep were higher on weekends (p < 0.05). Males, older age groups, and unemployed people spent less time in PA and more time in SB, compared with other population groups (p < 0.05). We found a relatively large increase in SB (mean difference [d] = 39.64 min/day; 95% CI: 36.18, 42.98) and decrease in PA (d = 54.33 min/day; 95% CI: -58.88, -49.30) over time. These findings were consistent across most sociodemographic groups, with the most concerning shifts from active to sedentary lifestyle found among people with a higher education degree and on weekends.

CONCLUSIONS: Our findings revealed a shift to a more sedentary lifestyle in the Thai population. Public health interventions should focus on improving time use among males, older age groups, and unemployed people, while preventing the rapid decrease in PA and increase in SB among those with a higher education degree and on weekends.

PMID:36693050 | DOI:10.1371/journal.pone.0280957

Chemistry. 2023 Jan 24. doi: 10.1002/chem.202203611. Online ahead of print.

ABSTRACT

For better understanding the intrinsic reactivity of organozinc reagents, we have examined the protolysis of the isolated zincate ions Et3Zn-, Et2Zn(OH)-, and Et2Zn(OH)2Li- by 2,2,2-trifluoroethanol in the gas phase. The protonation of the hydroxy groups and the release of water proceed much more efficiently than the protonation of the ethyl groups and the liberation of ethane. Quantum-chemical computations and statistical-rate theory calculations fully reproduce the experimental findings and attribute the lower reactivity of the more basic ethyl moiety to higher intrinsic barriers, which override the thermodynamic preference for its protonation. Thus, our minimalistic gas-phase model provides evidence for the intrinsically low reactivity of organozinc reagents toward proton donors and helps to explain their remarkable kinetic stability against moisture and even protic media.

PMID:36692992 | DOI:10.1002/chem.202203611

J Chem Theory Comput. 2023 Jan 24. doi: 10.1021/acs.jctc.2c00648. Online ahead of print.

ABSTRACT

Experimental studies of charge transport through single molecules often rely on break junction setups, where molecular junctions are repeatedly formed and broken while measuring the conductance, leading to a statistical distribution of conductance values. Modeling this experimental situation and the resulting conductance histograms is challenging for theoretical methods, as computations need to capture structural changes in experiments, including the statistics of junction formation and rupture. This type of extensive structural sampling implies that even when evaluating conductance from computationally efficient electronic structure methods, which typically are of reduced accuracy, the evaluation of conductance histograms is too expensive to be a routine task. Highly accurate quantum transport computations are only computationally feasible for a few selected conformations and thus necessarily ignore the rich conformational space probed in experiments. To overcome these limitations, we investigate the potential of machine learning for modeling conductance histograms, in particular by Gaussian process regression. We show that by selecting specific structural parameters as features, Gaussian process regression can be used to efficiently predict the zero-bias conductance from molecular structures, reducing the computational cost of simulating conductance histograms by an order of magnitude. This enables the efficient calculation of conductance histograms even on the basis of computationally expensive first-principles approaches by effectively reducing the number of necessary charge transport calculations, paving the way toward their routine evaluation.

PMID:36692968 | DOI:10.1021/acs.jctc.2c00648

JMIR Res Protoc. 2023 Jan 24;12:e38213. doi: 10.2196/38213.

ABSTRACT

BACKGROUND: Malaria and HIV, 2 of the world’s deadliest diseases, share a lot of territory in sub-Saharan Africa.

OBJECTIVE: This study seeks to investigate the effect of HIV on the immune response to malaria infection among pregnant women in Kumba in the southwest region (SWR) of Cameroon. The study aims to determine the prevalence of malaria infection, assess the occurrence of Plasmodium falciparum genetic diversity, and evaluate the antibody (immunoglobulin [Ig]G and IgM: apical membrane antigen-1 [AMA1], merozoite surface protein [MSP]1, MSP2, MSP3, and erythrocyte-binding antigen [EBA]175) and cytokine (interleukin [IL]-10, tumor necrosis factor alpha [TNF-α], and interferon gamma [IFNγ]) response to malaria infection among pregnant women with and without HIV in Kumba.

METHODS: The study will be a hospital-based cross-sectional design that will run from March 2022 to February 2023. It will recruit pregnant women with and without HIV who are in their third trimester of pregnancy. The study will be carried out in 5 health institutions in Kumba: General Hospital Kumba, Presbyterian Hospital Kumba, District Hospital Kumba-town, Kossala Integrated Health Center Kumba, and Catholic Hospital Kumba. About 3 mL of the mother’s venous blood, placental blood, and baby cord blood will be collected from each pregnant women at the point of delivery. Microscopy, rapid diagnostic tests (RDTs), and nested polymerase chain reaction (PCR) will be performed to identify the malaria parasite in all the samples, and nested PCR targeting the different genetic diversity markers for P. falciparum will also be performed. Furthermore, sequencing will be performed to study the nucleotide sequence of different alleles, and the genetic diversity of the alleles responsible for malaria infection among pregnant women will be assessed. A multiplex assay will be conducted to analyze the peripheral blood plasma and cord blood plasma for the cytokine and total antibody response to malaria infection among pregnant women with and without HIV. The questionnaire for data collection will be pretested at the Kumba District Hospital, and ethical clearance will be obtained from the University of Buea and the Regional Delegation of Public Health for the SWR. Data will be analyzed using SPSS Statistics and STATA. All P values <.05 will be considered statistically significant. BioEdit 7.0.0 software will be used to align the nucleotide sequences of different genes after sequencing. Phylogenetic tree searching will be conducted using the maximum-likelihood (ML) method in MEGA V6.0.

RESULTS: The project started in March 2022 and will end in February 2023. Presently, three-fourth of the project funding has been disbursed to date. A total of 218 participants have been enrolled: 193 (88.5%) women without HIV and 25 (11.5%) women with HIV. Between February 2023 and March 2024, the following results will be ready for publication: maternal-neonatal malaria prevalence among pregnant women and babies in Kumba, the effect of HIV on (1) P. falciparum genetic diversity among pregnant women in Kumba, (2) the maternal and neonatal immune response to MSP1, MSP2, and EBA175 IgG antibody response to P. falciparum-caused malaria infection among pregnant women, and (3) the maternal and neonatal pro-inflammatory and anti-inflammatory cytokine response to malaria infection.

CONCLUSIONS: HIV infection increases the prevalence of malaria infection among pregnant women and also influences the genetic diversity of P. falciparum, with MSP1 alleles being the most prevalent. HIV infection also reduces the antibody response to malaria infection, as well as altering the level of pro-inflammatory and anti-inflammatory responses to malaria infection.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38213.

PMID:36692923 | DOI:10.2196/38213

J Manag Care Spec Pharm. 2023 Jan 24:1-10. doi: 10.18553/jmcp.2023.22191. Online ahead of print.

ABSTRACT

BACKGROUND: The Disease Recovery Evaluation and Modification study (DREaM; NCT02431702) assessed the benefit of initiating paliperidone palmitate (PP), a long-acting injectable antipsychotic, in patients with recent-onset schizophrenia or schizophreniform disorder. OBJECTIVE: To determine whether reductions in psychiatric hospitalizations with early initiation of PP vs oral antipsychotic (OAP) therapy observed in a DREaM post hoc analysis are transportable to a real-world population of patients with recent-onset schizophrenia. METHODS: Patients enrolled in DREaM were randomized to receive OAP or PP for 9 months, after which OAP recipients were re-randomized to receive OAP or PP for another 9 months. We used this design to form treatment arms: OAP-OAP, OAP-PP, and PP-PP. Inclusion/exclusion criteria were used to identify a Medicaid Managed Care (MMC) OAP-treated cohort of 1,000 patients diagnosed with schizophrenia using IBM Truven databases from 2015 to 2019. The MMC cohort was combined with the subset of patients diagnosed with schizophrenia enrolled in DREaM from US sites (N = 45, 43, and 44 for OAP-OAP, OAP-PP, and PP-PP, respectively). Propensity scores for the MMC cohort were estimated using baseline variables identified via double-lasso regression. Estimated propensity scores were used to weight psychiatric hospitalizations in the DREaM OAP-OAP group and compared with observed MMC OAP cohort psychiatric hospitalizations. After the successful calibration of the DREaM OAP-OAP group, similar approaches were taken for the OAP-PP and PP-PP groups to transport DREaM effects to MMC data. RESULTS: Standardized mean differences in baseline covariates between DREaM treatment arms and MMC groups were substantially reduced after calibration. The 18-month cumulative numbers of psychiatric hospitalizations per patient (SE) were 0.83 (0.14) for the MMC cohort, 0.43 (0.14) for the unweighted OAP-OAP, and 0.80 (0.37) for the calibrated OAP-OAP. The difference between the calibrated OAP-OAP and MMC was not statistically significant (difference, 0.03 [95% CI = -0.67 to 0.81]), indicating successful calibration. The mean difference in 18-month cumulative psychiatric hospitalizations relative to the MMC cohort was -0.77 (95% CI = -1.08 to -0.47) for OAP-PP and -0.83 (95% CI = -1.15 to -0.60) for PP-PP. CONCLUSIONS: Our study demonstrates that results from the DREaM OAP-OAP group reflect psychiatric hospitalizations in a real-world population when calibrated using specific baseline characteristics. Transporting the DREaM effects, we find that using OAP-PP and PP-PP treatment strategies for patients with recent-onset schizophrenia in the MMC population could reduce psychiatric hospitalizations compared with the use of OAP. These findings, along with the potential reduction in associated costs, should be considered when assessing the value of PP formulations. DISCLOSURES: Dr Basu reports consulting fees through Salutis Consulting LLC related to this work. Dr Mavros is a former employee of the Janssen Pharmaceutical Companies of Johnson & Johnson, Inc, and holds stock in the company. Ms Benson, Dr Fu, Ms Patel, and Dr Brown are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson. This research was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; collection, analysis, and interpretation of data; and development and review of the manuscript. All authors had full access to the study data and take responsibility for data integrity and the accuracy of the analyses. All authors provided direction and comments on the manuscript, reviewed and approved the final version prior to submission, made the final decision about where to publish these data, and approved submission to this journal.

PMID:36692909 | DOI:10.18553/jmcp.2023.22191

Chin Med J (Engl). 2023 Jan 25. doi: 10.1097/CM9.0000000000002435. Online ahead of print.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) screening is effective in reducing CRC incidence and mortality. The aim of this study was to retrospectively determine and compare the detection rate of adenomas, advanced adenomas (AAs) and CRCs, and the number needed to screen (NNS) of individuals in an average-risk Chinese population of different ages and genders.

METHODS: This was a retrospective study performed at the Institute of Health Management, Chinese People’s Liberation Army General Hospital. Colonoscopy results were analyzed for 53,152 individuals finally enrolled from January 2013 to December 2019. The detection rate of adenomas, AAs, or CRCs was computed and the characteristics between men and women were compared using chi-squared test.

RESULTS: The average age was 48.8 years (standard deviation [SD], 8.5 years) for men and 50.0 years (SD, 9.0 years) for women, and the gender rate was 66.27% (35,226) vs. 33.73% (17,926). The detection rates of adenomas, AAs, serrated adenomas, and CRCs were 14.58% (7750), 3.09% (1641), 1.23% (653), and 0.59% (313), respectively. Men were statistically significantly associated with higher detection rates than women in adenomas (17.20% [6058/35,226], 95% confidence interval [CI] 16.74-17.53% vs. 9.44% [1692/17,926], 95% CI 8.94-9.79%, P < 0.001), AAs (3.72% [1309], 95% CI 3.47-3.87% vs. 1.85% [332], 95% CI 1.61-2.00%, P < 0.001), and serrated adenomas (1.56% [548], 95% CI 1.43-1.69% vs. 0.59% [105], 95% CI 0.47-0.70%, P < 0.001). The detection rate of AAs in individuals aged 45 to 49 years was 3.17% (270/8510, 95% CI 2.80-3.55%) in men and 1.69% (69/4091, 95% CI 1.12-1.86%) in women, and their NNS was 31.55 (95% CI 28.17-35.71) in men and 67.11 (95% CI 53.76-89.29) in women. The NNS for AAs in men aged 45 to 49 years was close to that in women aged 65 to 69 years (29.07 [95% CI 21.05-46.73]).

CONCLUSIONS: The detection rates of adenomas, AAs, and serrated adenomas are high in the asymptomatic population undergoing a physical examination and are associated with gender and age. Our findings will provide important references for effective population-based CRC screening strategies in the future.

PMID:36692899 | DOI:10.1097/CM9.0000000000002435

Neurol Res. 2023 Jan 24:1-9. doi: 10.1080/01616412.2022.2158640. Online ahead of print.

ABSTRACT

BACKGROUND: Observational studies showed renal function had associations with Alzheimer’s disease (AD), Parkinson’s disease (PD), Lewy body dementia (LBD) and multiple sclerosis (MS). However, it is unknown whether these associations are causal.

METHODS: We use a two-sample Mendelian randomization (MR) analysis to investigate causal relationships between renal function and 6 neurodegenerative diseases (NDDs): AD (including familial AD), PD, LBD, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and MS. Blood urea nitrogen (BUN), chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) were used to measure renal function. The inverse-variance weighted (IVW) was the predominant estimation method. The results were further validated using sensitivity analysis (i.e. MR Egger regression, Cochran Q statistic of IVW, and leave-one-out method).

RESULTS: There was no indication of any causative relationship of BUN, CKD, or eGFR with AD, familial AD, PD, LBD, FTD and ALS (all P values >0.05). The IVW analysis demonstrated a causal relationship between eGFR and MS [odds ratio (OR), 4.89; 95% confidence interval (CI), 1.43 to 16.71; P = 0.01] that was not verified in the MR-Egger and weighted median (all P values >0.05). However, no causal association of MS with BUN (OR, 0.91; 95% CI, 0.40-2.07; P = 0.82) and CKD (OR,1.04; 95% CI, 0.88-1.23; P = 0.66) was found. There was no single SNP that affects the overall trend.

CONCLUSIONS: Our study showed that reduced eGFR was related to MS. The value of this study is that it provides a direction for further research on the relationship between reduced eGFR and MS.

PMID:36692889 | DOI:10.1080/01616412.2022.2158640

JAMA Netw Open. 2023 Jan 3;6(1):e2252109. doi: 10.1001/jamanetworkopen.2022.52109.

ABSTRACT

IMPORTANCE: Workplace bullying is associated with mental disorders and suicidality in civilians, but few studies have examined associations of bullying with these outcomes among military personnel.

OBJECTIVE: To evaluate associations of being bullied or hazed during deployment with major depressive disorder (MDD), intermittent explosive disorder, posttraumatic stress disorder (PTSD), suicidal ideation, and substance use disorder (SUD).

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) New Soldier Study (NSS; April 1, 2011, to November 30, 2012) and wave 1 of the STARRS Longitudinal Study (STARRS-LS1; September 1, 2016, to April 30, 2018). A computerized survey administered at 3 US Army installations (NSS) and a web/telephone survey (STARRS-LS1) were used to collect data. Data were analyzed from October 11, 2021, to October 28, 2022. The STARRS-LS1 recruited a probability sample of active-duty soldiers and veterans who had participated in Army STARRS baseline surveys while on active duty (weighted response rate, 35.6%). Respondents whose baseline was the NSS and who had deployed to a combat theater at least once were eligible for this study.

EXPOSURES: Being bullied or hazed during a combat deployment.

MAIN OUTCOMES AND MEASURES: The primary outcomes were MDD, intermittent explosive disorder, PTSD, and suicidal ideation in the 12 months before STARRS-LS1 and SUD in the 30 days before STARRS-LS1, assessed with items from the Composite International Diagnostic Interview Screening Scales, PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and Columbia-Suicide Severity Rating Scale. Logistic regression was used to estimate associations of bullying or hazing exposure with the outcomes.

RESULTS: The 1463 participants were predominantly male (weighted percentage [SE], 90.4% [0.9%]) and had a mean (SE) age of 21.1 (0.1) years at baseline. At STARRS-LS1, 188 respondents (weighted percentage [SE], 12.2% [1.1%]) reported bullying or hazing during deployment. Weighted outcome prevalences were 18.7% (1.3%) for MDD, 5.2% (0.9%) for intermittent explosive disorder, 21.8% (1.5%) for PTSD, 14.2% (1.2%) for suicidal ideation, and 8.7% (1.0%) for SUD. In models that adjusted for baseline sociodemographic and clinical characteristics and other potential traumas, exposure to bullying or hazing was significantly associated with MDD (adjusted odds ratio [aOR], 2.92; 95% CI, 1.74-4.88), intermittent explosive disorder (aOR, 2.59; 95% CI, 1.20-5.59), PTSD (aOR, 1.86; 95% CI, 1.23-2.83), suicidal ideation (aOR, 1.91; 95% CI, 1.17-3.13), and SUD (aOR, 2.06; 95% CI, 1.15-3.70).

CONCLUSIONS AND RELEVANCE: In this cohort study of combat-deployed soldiers, reports of being bullied or hazed during deployment were associated with mental disorders and suicidal thoughts. Recognition of these associations may inform efforts to prevent and address mental health problems among service members.

PMID:36692883 | DOI:10.1001/jamanetworkopen.2022.52109