Nevin Manimala

Clin Transl Sci. 2022 Nov 5. doi: 10.1111/cts.13442. Online ahead of print.

ABSTRACT

Novel druggable targets are warranted for Inflammatory bowel disease (IBD) treatment. We aimed to identify novel circulating proteins with causal associations with the risk of IBDs and provide potential therapeutic targets for IBD treatment. We performed a two-sample Mendelian randomization study to explore the associations of 55 circulating biomarkers on the risk of IBD, Crohn’s disease (CD), and ulcerative colitis (UC) by leveraging the summary statistics from large genome-wide association studies and protein quantitative trait loci studies. The individual estimate was pooled together by meta-analyses to estimate the causal effects of each outcome. In univariable MR, we identified several circulating proteins showed potential correlation with IBD, UC, and CD. Of note, we observed that a genetically proxied increased level of ST2 was associated with an elevated risk of IBD (odds ratios [ORs] 1.133, 95% CI 1.091-1.176, P < 0.0001), CD (ORs 1.188, 95% CI 1.103-1.281, P < 0.0001), and UC cohorts (ORs 1.087, 95% CI 1.050-1.125, P < 0.0001). Additionally, we observed a consistent positive correlation between the level of CSF-1 and the increased risk of IBD in individual MR, with statistically significant causal associations in the meta-analyses with ORs equal to 1.217 (IBD, 95% CI 1.115-1.328, P < 0.0001), 1.223 (CD, 95% CI 1.082-1.382, P = 0.0013), and 1.179 (UC, 95% CI 1.055-1.317, P = 0.0037). This study provided evidence for potential casual associations between circulating ST2, CSF-1 levels and increased risks of IBD, UC, and CD, implicating potential treatment targets for IBD and subtypes.

PMID:36333983 | DOI:10.1111/cts.13442

Am J Hum Biol. 2022 Nov 5:e23830. doi: 10.1002/ajhb.23830. Online ahead of print.

ABSTRACT

OBJECTIVES: We aim to contribute to the literature reporting tests of selection in utero. The theory of reproductive suppression predicts that natural selection would conserve mechanisms, referred to collectively as selection in utero, that spontaneously abort fetuses unlikely to thrive as infants in the prevailing environment. Tests of this prediction include reports that women give birth to fewer than expected male twins, historically among the frailest of infants, during stressful times. The onset of the COVID-19 pandemic in the United States in Spring 2020 demonstrably stressed the population. We test the hypothesis that conception cohorts in gestation at the onset of the pandemic in the United States yielded fewer than expected live male twin births.

METHODS: We retrieved deidentified data on the universe of live births in the United States from the National Center for Health Statistics birth certificate records. We applied Box-Jenkins time-series methods to the twin secondary sex ratio computed for 77 monthly conception cohorts spanning August 2013 to December 2019 to detect outlying cohorts in gestation at the onset of the pandemic.

RESULTS: The twin secondary sex ratio fell below expected values in three conception cohorts (i.e., July, September, and October 2019, all p < .05) exposed in utero to the onset of the pandemic.

CONCLUSIONS: Our results add to prior findings consistent with selection in utero. The role of selection in utero in shaping the characteristics of live births cohorts, especially during the COVID-19 pandemic, warrants further scrutiny.

PMID:36333973 | DOI:10.1002/ajhb.23830

Pharm Stat. 2022 Nov 5. doi: 10.1002/pst.2272. Online ahead of print.

ABSTRACT

Designing Phase I clinical trials is challenging when accrual is slow or sample size is limited. The corresponding key question is: how to efficiently and reliably identify the maximum tolerated dose (MTD) using a sample size as small as possible? We propose model-assisted and model-based designs with adaptive intrapatient dose escalation (AIDE) to address this challenge. AIDE is adaptive in that the decision of conducting intrapatient dose escalation depends on both the patient’s individual safety data, as well as other enrolled patient’s safety data. When both data indicate reasonable safety, a patient may perform intrapatient dose escalation, generating toxicity data at more than one dose. This strategy not only provides patients the opportunity to receive higher potentially more effective doses, but also enables efficient statistical learning of the dose-toxicity profile of the treatment, which dramatically reduces the required sample size. Simulation studies show that the proposed designs are safe, robust, and efficient to identify the MTD with a sample size that is substantially smaller than conventional interpatient dose escalation designs. Practical considerations are provided and R code for implementing AIDE is available upon request.

PMID:36333972 | DOI:10.1002/pst.2272

Autism Res. 2022 Nov 5. doi: 10.1002/aur.2847. Online ahead of print.

ABSTRACT

The current study aimed at testing and developing alternative short versions of autism spectrum quotient (AQ-10) (adult [self-report], adult [parent-report], adolescent, and child versions) for use in Hong Kong. First, the various versions of AQ-10 developed in the United Kingdom (the AQ-10-UK) were applied to Hong Kong Chinese samples and demonstrated satisfactory discriminative power (AUCs 0.77-0.94). Second, the Hong Kong Chinese versions of AQ-10 (AQ-10-HK) were developed, using the same methodology as in the original UK study. There were some changes in the choice of items and cut-offs. The AQ-10-HK demonstrated slightly greater discriminative power (AUCs 0.88-0.97) to that of the AQ-10-UK, but the differences in AUCs were not statistically significant. Compared to the corresponding full-length versions, both the UK and HK short forms did not seem to lose any significant discriminative power. Yet, the various versions of AQ, be they the full-length or AQ-10, appeared to consistently exhibit slightly smaller AUCs with the Hong Kong Chinese samples than with the UK samples. So, this study found both cross-cultural similarities and differences. The AQ-10-HK was recommended for local practice to maximize the advantage gained. Yet, for international multi-site research collaboration, involving the UK and HK, the original AQ-10-UK can be used for direct comparison of data.

PMID:36333966 | DOI:10.1002/aur.2847

J Med Philos. 2022 Nov 5;47(4):530-539. doi: 10.1093/jmp/jhac012.

ABSTRACT

One way in which bioethicists can benefit the medical community is by clarifying the concept of disorder. Since insurance companies refer to the DSM for whether a patient should receive assistance, one must consider the consequences of one’s concept of disorder for who should be provided with care. I offer a refinement of Jerome Wakefield’s hybrid concept of disorder, the harmful dysfunction analysis. I criticize both the factual component and the value component of Wakefield’s account and suggest how they might be improved. I propose that the factual component should be statistical variation analyzed in multilevel and chronological compilations of physiological data. I propose that the value component should prioritize the individual’s authority regarding the experience of suffering from a physiological condition. My account preserves the insight of using a factual and a value component while avoiding the problems that Wakefield’s original account faces.

PMID:36333929 | DOI:10.1093/jmp/jhac012

Pacing Clin Electrophysiol. 2022 Nov 4. doi: 10.1111/pace.14616. Online ahead of print.

ABSTRACT

BACKGROUND: Atrial fibrillation and flutter are often treated with external electrical cardioversion (ECV) in patients with potentially electrically sensitive cardiovascular implantable electronic devices (CIED). Long-term follow-up data on contemporary CIED undergoing ECV is sparse. The aim is to investigate shock-related complications and impact on CIEDs.

METHODS: All ECV procedures from 2010 to 2020 in patients with CIED performed at a tertiary university hospital were identified in the Danish National Patient Registry. Changes in device measurements after ECV were retrospectively studied and procedure-related complications were identified by review of medical records.

RESULTS: We analyzed 763 ECV procedures in 372 patients, median device implant time 1.9 year. The mean age of patients was 69.9 ± 9.9 years of which 73.4% were men. We identified two cases of device programming changes and four cases of premature battery depletion (≤3 years after device implant). Minor changes in device measurements were found for impedances, sensing, and pacing thresholds. No patients died due to ECV-related device dysfunctions within the first 12 months after cardioversions.

CONCLUSION: External cardioversion in patients with contemporary pacemakers and implantable cardioverter-defibrillators seems safe in the majority of patients. Clinically important changes in device function following cardioversion were rarely observed but may be critical for device function. In an observational study, causality between cardioversion and device dysfunction cannot be established. For patient safety, we suggest that routine device interrogation after cardioversion still should be part of standard care. This article is protected by copyright. All rights reserved.

PMID:36333921 | DOI:10.1111/pace.14616

Am J Mens Health. 2022 Nov-Dec;16(6):15579883221130193. doi: 10.1177/15579883221130193.

ABSTRACT

Alcohol consumption among humans has lasted for several centuries. In Africa, drinking is normal for men despite its consequences. The study is aimed at determining the rate of alcohol consumption in the study area, health consequences of alcoholism and factors that reinforce alcoholism among men. The study, which adopted descriptive survey design, was conducted at Ezeagu, Southeast Nigeria. Quota sampling was used to select participants (400). A questionnaire was used to collect data, and analysis was done using descriptive statistics. The data revealed that men in the area are heavy drinkers, but their level of awareness about its health consequences is low. The study shows that the factors preventing men from quitting alcohol consumption include peer group influence and traditional ceremonies/festivals. The study concludes that alcoholism has adverse health consequences. Men hardly quit alcohol consumption because of factors within their communities, therefore; raising the awareness level about the adverse health implications of alcoholism is a necessity.

PMID:36333918 | DOI:10.1177/15579883221130193

Environ Microbiol. 2022 Nov 4. doi: 10.1111/1462-2920.16271. Online ahead of print.

ABSTRACT

The comprehension of microbial interactions is one of the key challenges in marine microbial ecology. This study focused on exploring chemical interactions between the toxic dinoflagellate Prorocentrum lima and a filamentous fungal species, Aspergillus pseudoglaucus, which has been isolated from the microalgal culture. Such interspecies interactions are expected to occur even though they were rarely studied. Here, a co-culture system was designed in a dedicated microscale marine-like condition. This system allowed to explore microalgal-fungal physical and metabolic interactions in presence and absence of the bacterial consortium. Microscopic observation showed an unusual physical contact between the fungal mycelium and dinoflagellate cells. To delineate specialized metabolome alterations during microalgal-fungal co-culture metabolomes were monitored by high-performance liquid chromatography coupled to high-resolution mass spectrometry. In-depth multivariate statistical analysis using dedicated approaches highlighted (1) the metabolic alterations associated with microalgal-fungal co-culture, and (2) the impact of associated bacteria in microalgal metabolome response to fungal interaction. Unfortunately, only a very low number of highlighted features were fully characterised. However, an up-regulation of the dinoflagellate toxins okadaic acid and dinophysistoxin 1 was observed during co-culture in supernatants. Such results highlight the importance to consider microalgal-fungal interactions in the study of parameters regulating toxin production. This article is protected by copyright. All rights reserved.

PMID:36333915 | DOI:10.1111/1462-2920.16271

Biophys J. 2022 Nov 3:S0006-3495(22)00903-1. doi: 10.1016/j.bpj.2022.11.005. Online ahead of print.

ABSTRACT

Molecular Dynamics (MD) simulations have become the predominant computational analysis method in membrane biophysics, as this technique is uniquely suited for investigations of complex molecular systems through the relevant physical principles. Owing to continued improvements in scope and performance, the trajectories generated through this approach contain ever-increasing amounts of information, which must be synthesized and simplified in post-analysis using tools that are not only mechanistically insightful but also computationally efficient and highly scalable. Here, we introduce MOSAICS, a self-contained high-performance suite of C++ software tools designed for advanced analyses of lipid bilayer structure and dynamics from MD trajectories. MOSAICS is to our knowledge the most comprehensive software suite of this kind, enabling analysis of a wide array of morphological and kinetic properties, for both simple and complex membranes, irrespective of system size or resolution. Importantly, MOSAICS is designed to provide spatial distributions of all computed quantities, with built-in masking tools, noise filtering and statistical-significance metrics to facilitate quantitative interpretations of the trajectory data; it is also fully parallelized and can therefore leverage the capabilities of supercomputing facilities. Despite its technical sophistication, MOSAICS is user-friendly and requires minimal computational expertise, making it accessible to researchers of all skill levels.

PMID:36333911 | DOI:10.1016/j.bpj.2022.11.005

Med Educ Online. 2023 Dec;28(1):2141602. doi: 10.1080/10872981.2022.2141602.

ABSTRACT

BACKGROUND & OBJECTIVES: In 2021, the USA recorded 100,000 annual deaths from drug overdose, representing the most frequent cause of death in adults under age 55. The integration of care for substance use disorders (SUDs) into undergraduate medical education is not well established. It is unclear whether a short course on management of opioid use disorder (OUD) offered to fourth year medical students could increase graduating students’ knowledge and preparedness to treat these disorders.

METHODS: We designed a 2-hour interactive case-based session on patient care for OUD and delivered it virtually as part of a Transition to Residency course. A retrospective pre-/post-test assessment instrument determined the impact of this session on students’ perceived knowledge, confidence, and intention to seek further educational opportunities for OUD.

RESULTS: Of 144 participants, 58 students (40.3%) completed the retrospective pre-/post- survey. There were statistically significant improvements in perceived knowledge and attitudes on the 12-item survey. The largest gains in perceived knowledge on a 5-point scale occurred in the categories regarding buprenorphine induction (pre 2.9; post 4.22; p < 0.001), managing inpatient opioid withdrawal (pre 2.84; post 4.27; p < 0.001), and the role of methadone in treating withdrawal (pre 3.16; post 4.29; p < 0.001). All (n = 58) survey respondents would recommend the training to a colleague and felt that the session would benefit their professional practice. Over 90% (93.1%) of respondents planned on seeking additional SUD learning opportunities during residency.

CONCLUSIONS: A 2-hour interactive case-based teaching session delivered to medical students improved perceived knowledge, attitudes, and future interest in obtaining education around OUD. As the opioid epidemic shows no sign of abating, we would advocate for the inclusion SUD education as part of Transition to Residency courses.

PMID:36333902 | DOI:10.1080/10872981.2022.2141602