Nevin Manimala

J Hum Genet. 2022 Jun 20. doi: 10.1038/s10038-022-01051-y. Online ahead of print.

ABSTRACT

Although several genes involved in the development of Tetralogy of Fallot have been identified, no genetic diagnosis is available for the majority of patients. Low statistical power may have prevented the identification of further causative genes in gene-by-gene survey analyses. Thus, bigger samples and/or novel analytic approaches may be necessary. We studied if a joint analysis of groups of functionally related genes might be a useful alternative approach. Our reanalysis of whole-exome sequencing data identified 12 groups of genes that exceedingly contribute to the burden of Tetralogy of Fallot. Further analysis of those groups showed that genes with high-impact variants tend to interact with each other. Thus, our results strongly suggest that additional candidate genes may be found by studying the protein interaction network of known causative genes. Moreover, our results show that the joint analysis of functionally related genes can be a useful complementary approach to classical single-gene analyses.

PMID:35718831 | DOI:10.1038/s10038-022-01051-y

Mol Biol Rep. 2022 Jun 19. doi: 10.1007/s11033-022-07691-9. Online ahead of print.

ABSTRACT

BACKGROUND: Mungbean yellow mosaic India virus (MYMIV) is a representative of the genus begomovirus/Begomoviridae, which is prevalent in the northern part of Indian subcontinent causing yellow mosaic disease (YMD). This virus is rapidly evolving and breaking the resistance in the advanced lines causing huge economic losses in the pulse production. In this context, the present investigation on characterization of the causal organism of YMD was undertaken METHODS AND RESULTS: A novel recombinant isolate (YMV-BG-BPT) causing YMD was identified from blackgram in Andhra Pradesh, southern peninsular region of India. The association of a bipartite begomovirus with the disease was done by sequence analyses of the cloned full-length genome. The full length genome sequences were submitted in NCBI GenBank with accession numbers MZ235792 (DNA-A) and MZ356197 (DNA-B). The sequence analysis of DNA-A of YMV-BG-BPT showed maximum of 99.12% similarity at nucleotide level with Mungbean yellow mosaic India virus (MYMIV) isolate reported from Tamil Nadu (KC911719), India which is also confirmed by clustering pattern in phylogenic analysis and DNA-B showed 95.79% with Mungbean yellow mosaic virus (MYMV) isolate reported from Tamil Nadu (KP319016) and 95.05% with MYMIV isolate reported from Karnataka (MT027037). The huge variation in DNA-B lead us to suspect a recombination in DNA-B, where a recombination event in the CR, region coding for nuclear shuttle protein and movement protein of DNA B was detected in which MYMV-BG-AP-IND (KF928962) and MYMIV-GG-CH-IND (MN020536) have been identified as major and minor parents, respectively.

CONCLUSION: Overall, the present study revealed occurrence of MYMIV with recombinant DNA B component in southern peneinsular India.

PMID:35718827 | DOI:10.1007/s11033-022-07691-9

Prog Orthod. 2022 Jun 20;23(1):19. doi: 10.1186/s40510-022-00414-7.

ABSTRACT

OBJECTIVE: The stability of the transverse expansion in passive self-ligating bracket treatments is a debated topic in orthodontics. However, to date, only 3 reports are available in the literature, with the maximum follow-up of 3 years after the end of therapy. The present study aims to evaluate the stability of orthodontic treatment with self-ligating brackets in a 6-year follow-up period of time.

MATERIALS AND METHODS: A sample of 56 non-extractive cases (of whom 33 females, mean age 16.9, SD = 9.0 years) consecutively treated with Damon® system was retrospectively selected. All patients received fixed retainers from canine to canine in both arches at the end of treatment, and no removable retainers were provided. The mean values of the transverse intercusp, transverse centroid and transverse lingual distances were evaluated for all teeth from canines to second molars in both arches. Each measure was calculated at four timepoints: before treatment (T0), at the end of treatment (T1), one year after treatment (T2) and six years after treatment (T3). Transverse diameters were measured for all teeth, starting from the canines to the second molars, for a total of 1680 observations, and subsequently compared in order to evaluate intra-treatment and post-treatment modifications.

RESULTS: There were increases in all transverse dental measurements during active treatment. A statistically significant (p < .05) reduction of the transverse diameter was found, for upper and lower premolars, from T1 to T3.

CONCLUSION: The 6-year follow-up analysis detected that the initial transverse expansion showed a statistically significant relapse in premolars. No relapse was detected at the level of canines, due to the presence of fixed retainers, and minimal at first molars.

PMID:35718801 | DOI:10.1186/s40510-022-00414-7

Sci Rep. 2022 Jun 19;12(1):10306. doi: 10.1038/s41598-022-14312-9.

ABSTRACT

The dynamic of fluids and coolants in automobiles are achieved by enhancement in heat energy using ternary hybrid nanostructures. Ternary hybrid nanomaterial is obtained by suspension of three types of nanofluid (aluminum oxide, silicon dioxide and titanium dioxide) in base fluid (EG). Prime investigation is to address comparison study in thermal energy involving various flow models termed as Maxwell fluid and Williamson fluid. This exploration is carried out by partially ionized fluidic particles in the presence of ternary hybrid nanomaterial over cone. Heat transfer is carried out by heat source and thermal radiation. Equations regarding Ordinary differential are achieved from PDEs using variable transformations. The numerical consequences are obtained implementing finite element method. Flow into fluid particles is enhanced versus higher values of Hall and ion slip parameters. Thermal performance as well as flow performance for the case Williamson fluid is better than for case of Maxwell fluid. Production via energy is boosted versus heat source parameter.

PMID:35718797 | DOI:10.1038/s41598-022-14312-9

BMC Ophthalmol. 2022 Jun 20;22(1):268. doi: 10.1186/s12886-022-02484-x.

ABSTRACT

PURPOSE: Nystagmus is a disorder characterized by uncontrolled, rhythmic oscillations of the eyes. It often causes reduced visual function beyond reduced visual acuity alone. There is a paucity of literature regarding the public understanding of nystagmus, and there are no published data on the impact of the COVID-19 pandemic on people living with the condition. This study explores the self-reported impact of the COVID-19 pandemic on those with nystagmus, and examines both public understanding of how nystagmus affects people who have it and the perceptions of public understanding by those with the condition and their carers.

METHODS: A qualitative questionnaire was designed following a stakeholder engagement process. This questionnaire was advertised via social media platforms and charity websites to achieve widespread recruitment. Data were collected between November and December 2020. Participants were divided into two groups based on their response to the question: “Do you, or anyone you know well, have nystagmus?”. Questions were posed to participants in a purpose-built, branching survey. The resulting data were analyzed using descriptive and inferential statistical methods.

RESULTS: One thousand six hundred forty-five respondents were recruited, of which 849 (51.6%) answered “Yes” to the initial filtering question. Analysis showed that, broadly, public understanding of nystagmus differs from the perception of it by those with nystagmus and their carers, that the COVID-19 pandemic has had a significant impact on those with nystagmus, and that respondents who have met someone with nystagmus, even briefly, tend to have a greater understanding of the impact of the condition.

CONCLUSION: This study highlights the lack of public awareness regarding nystagmus and suggests opportunities to increase the awareness of nystagmus without the need for extensive knowledge of the condition. The COVID-19 pandemic has posed additional difficulties for those living with nystagmus, which is likely to be comparable among those with similar ocular disorders.

PMID:35718783 | DOI:10.1186/s12886-022-02484-x

BMC Med. 2022 Jun 20;20(1):208. doi: 10.1186/s12916-022-02407-z.

ABSTRACT

BACKGROUND: Recent guidelines recommended a systolic blood pressure (SBP) target of < 130 mmHg for patients with or without diabetes but without providing a lower bound. Our study aimed to explore whether additional clinical benefits remain at achieved blood pressure (BP) levels below the recommended target.

METHODS: We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) among the non-diabetic population and the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial among diabetic subjects. We used the propensity score method to match patients from the intensive BP group to those from the standard group in each trial. Individuals with different achieved BP levels from the intensive BP group were used as “reference.” For each stratum, the trial-specific primary outcome (i.e., composite outcome of myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure (HF), or cardiovascular death for SPRINT; non-fatal MI, non-fatal stroke, or cardiovascular death for ACCORD-BP) was compared by Cox regression.

RESULTS: A non-linear association was observed between the mean achieved BP and incidence of composite cardiovascular events, regardless of treatment allocation. The significant treatment benefit for primary outcome remained at SBP 110-120 mmHg (hazard ratio, 0.59 [95% CI, 0.46, 0.76] for SPRINT; 0.67 [0.52, 0.88] for ACCORD-BP) and SBP 120-130 mmHg for SPRINT (0.47 [0.34, 0.63]) but not for ACCORD-BP (0.93 [0.70, 1.23]). The results were similar for the secondary outcomes including all-cause mortality, cardiovascular mortality, MI, stroke, and HF. Intensive BP treatment benefits existed among patients maintaining a diastolic BP of 60-70 mmHg but were less distinct.

CONCLUSIONS: The treatment benefit persists at as low as SBP 110-120 mmHg irrespective of diabetes status. Achieved very low BP levels appeared to increase cardiovascular events and all-cause mortality.

PMID:35718771 | DOI:10.1186/s12916-022-02407-z

BMC Infect Dis. 2022 Jun 19;22(1):558. doi: 10.1186/s12879-022-07415-1.

ABSTRACT

BACKGROUND: A global pandemic has been declared for coronavirus disease 2019 (COVID-19), which has serious impacts on human health and healthcare systems in the affected areas, including Vietnam. None of the previous studies have a framework to provide summary statistics of the virus variants and assess the severity associated with virus proteins and host cells in COVID-19 patients in Vietnam.

METHOD: In this paper, we comprehensively investigated SARS-CoV-2 variants and immune responses in COVID-19 patients. We provided summary statistics of target sequences of SARS-CoV-2 in Vietnam and other countries for data scientists to use in downstream analysis for therapeutic targets. For host cells, we proposed a predictive model of the severity of COVID-19 based on public datasets of hospitalization status in Vietnam, incorporating a polygenic risk score. This score uses immunogenic SNP biomarkers as indicators of COVID-19 severity.

RESULT: We identified that the Delta variant of SARS-CoV-2 is most prevalent in southern areas of Vietnam and it is different from other areas in the world using various data sources. Our predictive models of COVID-19 severity had high accuracy (Random Forest AUC = 0.81, Elastic Net AUC = 0.7, and SVM AUC = 0.69) and showed that the use of polygenic risk scores increased the models’ predictive capabilities.

CONCLUSION: We provided a comprehensive analysis for COVID-19 severity in Vietnam. This investigation is not only helpful for COVID-19 treatment in therapeutic target studies, but also could influence further research on the disease progression and personalized clinical outcomes.

PMID:35718768 | DOI:10.1186/s12879-022-07415-1

BMC Med Educ. 2022 Jun 20;22(1):474. doi: 10.1186/s12909-022-03523-3.

ABSTRACT

INTRODUCTION: A validated instrument to assess the motivating factors influencing junior doctors’ medical specialist career choices is not available. The Motivators for Medical Specialist Career Choice Questionnaire (MMSCCQ) was developed and validated in the present study.

METHODS: An exploratory sequential mixed-methods study was conducted among house officers (HO) of a tertiary care hospital. A literature review was used to construct an interview guide. Seven HOs participated in an online, one-on-one audio-recorded in-depth interview (IDI). Seven sub-themes and 33 codes identified by thematic analyses were used to develop the MMSCCQ. The importance of each motivator was rated on a five-point Likert scale. The MMSCCQ was pretested, and a random sample of 262 house officers was invited to participate in an online survey. Psychometric evaluation was done using reliability statistics, and exploratory and confirmatory factor analyses.

RESULTS: The seven main themes identified by thematic analyses were labeled as factors related to ‘work schedule and personal life,’ ‘training opportunities’, ‘past work experiences’, ‘specialty characteristics’, ‘career prospects’, ‘patient care characteristics’, and ‘social factors.’ The highest ratings were given to “previous job experience” and “patient care traits. “The response rate was 71%, the mean age of the 185 HOs was 26.7 years (SD = 1.6). Females made up 63.8% of the population. The internal consistency for the overall questionnaire measured by Cronbach’s alpha was 0.85. Each construct demonstrated an acceptable internal consistency. Twenty-six of 33 items were maintained after an exploratory factor analysis was conducted, yielding 7 constructs with a 64.9% variance. Confirmatory factor analyses established the construct validity.

CONCLUSION: The MMSCCQ has acceptable reliability and construct validity. Further studies are needed to test psychometric properties in different settings.

PMID:35718765 | DOI:10.1186/s12909-022-03523-3

BMC Surg. 2022 Jun 20;22(1):234. doi: 10.1186/s12893-022-01683-z.

ABSTRACT

BACKGROUND: Several studies have discussed various methods of prepectoral direct-to-implant (DTI) breast reconstruction using an acellular dermal matrix (ADM) prosthesis to achieve full coverage. However, methods for anterior coverage have rarely been reported. In this study, prepectoral DTI breast reconstruction with complete anterior implant coverage was performed using a square piece of ADM. This study aimed to introduce our prepectoral DTI technique and determine its functional and cosmetic outcomes as well as compare them with those of existing subpectoral DTI techniques.

METHODS: This prospective comparative study focused on 29 patients (35 breasts) and 34 patients (35 breasts) who underwent breast reconstruction via subpectoral implant insertion (control group) and anterior coverage prepectoral implant insertion (anterior coverage group), respectively. Postoperative complications were noted, and breast symmetry was evaluated using the Vectra H2 three-dimensional scanner. The modified Kyungpook National University Hospital Breast-Q (KNUH Breast-Q) scale was used to assess the patient’s subjective satisfaction with the reconstruction and postoperative quality of life.

RESULTS: No remarkable differences in terms of complications (seroma, skin necrosis, nipple-areola complex necrosis, hematoma, capsular contracture, and infection) were noted in both groups. Compared with controls, considerably better results were observed among those in the anterior coverage group in terms of the mean drain removal period. Furthermore, those in the anterior coverage group showed greater symmetry on three-dimensional scans than the controls; however, this was not statistically significant. Subjective satisfaction and postoperative quality of life measured using the KNUH Breast-Q scale were not significantly different between both groups.

CONCLUSIONS: Considering its stability, faster recovery time, and cosmetic benefit, prepectoral breast reconstruction with anterior implant coverage using a single, large ADM is a good choice to perform breast reconstruction with implant insertion in patients who have undergone mastectomy.

LEVEL OF EVIDENCE: II.

PMID:35718764 | DOI:10.1186/s12893-022-01683-z

BMC Med Res Methodol. 2022 Jun 19;22(1):175. doi: 10.1186/s12874-022-01655-0.

ABSTRACT

BACKGROUND: Normalization process theory (NPT) has been widely used to better understand how new interventions are implemented and embedded. The NoMAD (Normalization Measurement Development questionnaire) is a 23-item NPT instrument based on NPT. As the NoMAD is a relatively new instrument, the objectives of this paper are: to describe the experience of implementing the NoMAD, to describe it being used as a feedback mechanism to gain insight into the normalization process of a complex health intervention, and to further explore the psychometric properties of the instrument.

METHODS: Health TAPESTRY was implemented in six Family Health Teams (total of seven sites) across Ontario. Healthcare team members at each site were invited to complete the NoMAD, and three general questions about normalization, six times over a 12-month period. Each site was then provided a visual traffic light summary (TLS) reflecting the implementation of the Health TAPESTRY. The internal consistency of each sub-scale and validity of the NoMAD were assessed. Learnings from the implementation of the NoMAD and subsequent feedback mechanism (TLS) are reported descriptively.

RESULTS: In total, 56 diverse health care team members from six implementation sites completed the NoMAD. Each used it at least once during the 12-month study period. The implementation of the NoMAD and TLS was time consuming to do with multiple collection (and feedback) points. Most (60%) internal consistency values of the four subscales (pooled across site) across each collection point were satisfactory. All correlations were positive, and most (86%) were statistically significant among NoMAD subscales. All but one correlation between the NoMAD subscales and the general questions were positive, and most (72%) were significant. Generally, scores on the subscales were higher at 12-month than baseline, albeit did not follow a linear pattern of change across implementation. Generally, scores were higher for experienced sites compared to first-time implementors.

CONCLUSION: Our experience would suggest fewer collection points; three timepoints spaced out by several months are adequate, if repeated administration of the NoMAD is used for feedback loops. We provide additional evidence of the psychometric properties of the NoMAD.

TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT03397836 .

PMID:35718763 | DOI:10.1186/s12874-022-01655-0