Category: Nevin Manimala

Genome Med. 2022 Aug 9;14(1):85. doi: 10.1186/s13073-022-01094-y.

ABSTRACT

BACKGROUND: Rare diseases collectively affect up to 10% of the population, but often lack effective treatment, and typically little is known about their pathophysiology. Major challenges include suboptimal phenotype mapping and limited statistical power. Population biobanks, such as the UK Biobank, recruit many individuals who can be affected by rare diseases; however, investigation into their utility for rare disease research remains limited. We hypothesized the UK Biobank can be used as a unique population assay for rare diseases in the general population.

METHODS: We constructed a consensus mapping between ICD-10 codes and ORPHA codes for rare diseases, then identified individuals with each rare condition in the UK Biobank, and investigated their age at recruitment, sex bias, and comorbidity distributions. Using exome sequencing data from 167,246 individuals of European ancestry, we performed genetic association controlling for case/control imbalance (SAIGE) to identify potential rare pathogenic variants for each disease.

RESULTS: Using our mapping approach, we identified and characterized 420 rare diseases affecting 23,575 individuals in the UK Biobank. Significant genetic associations included JAK2 V617F for immune thrombocytopenic purpura (p = 1.24 × 10^-13) and a novel CALR loss of function variant for essential thrombocythemia (p = 1.59 × 10^-13). We constructed an interactive resource highlighting demographic information ( http://www-personal.umich.edu/~mattpat/rareDiseases.html ) and demonstrate transferability by applying our mapping to a medical claims database.

CONCLUSIONS: Enhanced disease mapping and increased power from population biobanks can elucidate the demographics and genetic associations for rare diseases.

PMID:35945607 | DOI:10.1186/s13073-022-01094-y

Respir Res. 2022 Aug 9;23(1):202. doi: 10.1186/s12931-022-02126-2.

ABSTRACT

BACKGROUND: The efficacy and safety of complement inhibition in COVID-19 patients is unclear.

METHODS: A multicenter randomized controlled, open-label trial. Hospitalized COVID-19 patients with signs of systemic inflammation and hypoxemia (PaO₂/FiO₂ below 350 mmHg) were randomized (2:1 ratio) to receive standard of care with or without the C5 inhibitor zilucoplan daily for 14 days, under antibiotic prophylaxis. The primary outcome was improvement in oxygenation at day 6 and 15.

RESULTS: 81 patients were randomly assigned to zilucoplan (n = 55) or the control group (n = 26). 78 patients were included in the safety and primary analysis. Most were men (87%) and the median age was 63 years. The mean improvement in PaO₂/FiO₂ from baseline to day 6 was 56.4 mmHg in the zilucoplan group and 20.6 mmHg in the control group (mean difference + 35.8; 95% confidence interval (CI) – 9.4 to 80.9; p = 0.12), an effect also observed at day 15. Day 28 mortality was 9% in the zilucoplan and 21% in the control group (odds ratio 0.4; 95% CI 0.1 to 1.5). At long-term follow up, the distance walked in a 6-min test was 539.7 m in zilucoplan and 490.6 m in the control group (p = 0.18). Zilucoplan lowered serum C5b-9 (p < 0.001) and interleukin-8 (p = 0.03) concentration compared with control. No relevant safety differences between the zilucoplan and control group were identified.

CONCLUSION: Administration of zilucoplan to COVID-19 patients in this proof-of-concept randomized trial was well tolerated under antibiotic prophylaxis. While not reaching statistical significance, indicators of respiratory function (PaO₂/FiO₂) and clinical outcome (mortality and 6-min walk test) suggest that C5 inhibition might be beneficial, although this requires further research in larger randomized studies.

PMID:35945604 | DOI:10.1186/s12931-022-02126-2

Trials. 2022 Aug 9;23(1):637. doi: 10.1186/s13063-022-06583-4.

ABSTRACT

BACKGROUND: Dysmenorrhea is one of the most common disorders among young women. Medicinal herbs are one of the alternative methods for the treatment of dysmenorrhea. This study will investigate the effect of Rosa foetida extract, along with self-care behavior education on primary dysmenorrhea among female students of Babol University of medical sciences.

METHODS/DESIGN: A randomized clinical trial will be performed on single students, aged 18 to 24 years. The research samples will be divided into three groups. The students will receive self-care behavior education on dysmenorrhea. Following the education, two of the groups will receive Rosa foetida extract capsules and placebo capsules in two consecutive cycles every 8 h for two successive days, respectively. The capsules will have similar physical appearance. The third group will not receive any medication. Data will be collected through demographic characteristic questionnaire, visual analog scale, dysmenorrhea self-care behaviors scale questionnaire, pictorial chart, and menstrual distress scale questionnaire. In order to determine and compare the effect of pharmacological and educational interventions on the severity of dysmenorrhea in groups, an ANOVA analysis of variance test with repeated measures will be used by SPSS software version 22.

DISCUSSION: The results will show the effects of Rosa foetida extract along with self-care behavior education on primary dysmenorrhea, and beneficial effects that may be found in the trial of this plant may be of use for women with the same problem.

ETHICS AND DISSEMINATION: The study is approved by the Ethics Committee of Babol University of Medical Sciences (IR.MUBABOL.REC.1397.059).

TRIAL REGISTRATION: IRCT 20190318043086N1. Registered on 14 June 2019.

PMID:35945594 | DOI:10.1186/s13063-022-06583-4

BMC Oral Health. 2022 Aug 9;22(1):338. doi: 10.1186/s12903-022-02368-y.

ABSTRACT

BACKGROUND: The Tanaka and Johnson equation is commonly used in mixed dentition analysis. However, the analysis is based on a Caucasian population making clinical decisions challenging when used in different ethnic groups. This study developed a prediction equation based on a Kenyan population.

DESIGN: A descriptive cross-sectional study done in 68 13-17 years old Kenyans of African descent in two boarding secondary schools. Alginate impressions were taken, study models obtained, and mesiodistal tooth-widths measured on upper and lower study models from the first molar to the contralateral first molar. Descriptive statistics, paired t-tests and independent t-tests were conducted and Pearson product-moment correlation coefficients calculated (p < 0.05).

RESULTS: The mean age was 13.78 years (SD ± 0.70), females were 59%. The mesiodistal tooth-widths of the permanent canines and premolars were different between males and females (p ˂ 0.1). The Tanaka and Johnston equation significantly under-estimated the mesiodistal tooth-widths of the permanent canines and premolars (p ˂ 0.05). The addition of lower first permanent molars to the permanent lower incisors provided higher correlation coefficients than the Tanaka Johnston equation.

CONCLUSIONS: A new equation that includes the permanent lower incisors and first permanent molars as predictor teeth seems to be more suitable for mixed dentition analysis for this Kenyan population. A larger study is needed to validate these findings.

PMID:35945576 | DOI:10.1186/s12903-022-02368-y

BMC Oral Health. 2022 Aug 9;22(1):337. doi: 10.1186/s12903-022-02373-1.

ABSTRACT

BACKGROUND: The Sense of Coherence (SOC) construct has been used worldwide in oral health research, but rigorous factor analyses of the scale are scarce. We aim to test the dimensional structure of the Brazilian short version of the SOC scale with 13 items.

METHODS: This study is a secondary analysis of four independent cross-sectional Brazilian studies on oral health, using the 13-items SOC scale. Sample 1 was conducted on 1760 mothers and 1771 adolescents. Sample 2 comprised 1100 adults. Sample 3 had 720 adults and older individuals. Sample 4 comprised 664 adolescent students. Confirmatory Factor Analysis (CFA) was conducted on sample 1 to compare two models: 3-factor versus 1-factor. Because they were refuted, Exploratory Factor Analysis was implemented in samples 2 and 3. Modified models were tested in sample 4 using CFA. All analyses were conducted with MPlus version 7.11.

RESULTS: CFA of sample 1 resulted in an unacceptable fit (RMSEA = 0.12;CFI = 0.78; TLI = 0.73; and WRMR = 3.28) for 1-factor model and 3-factor (RMSEA = 0.10; CFI = 0.87; TLI = 0.84; and WRMR = 2.50). The EFA on samples 2 and 3 showed, respectively, two eigenvalues greater than 1 (4.11 and 1.56) and (4.32 and 1.42), but the scale items soc1, soc2 and soc3 formed an uninterpretable second factor. Another CFA, using sample 4, showed acceptable model fit after removing those three items and also soc11 (RMSEA = 0.05; CFI = 0.98; TLI = 0.99; and WRMR = 0.71).

CONCLUSION: The results indicate that the SOC-13 scale needs further adjustments. The one-factor model with nine items showed a good statistical fit, but the implications of excluding items should be further investigated, considering the scale’s content validity, cross-cultural adaptation and theoretical background.

PMID:35945574 | DOI:10.1186/s12903-022-02373-1

BMC Med Educ. 2022 Aug 9;22(1):610. doi: 10.1186/s12909-022-03678-z.

ABSTRACT

BACKGROUND: Complete denture, as an important restoration method for edentulism, is difficult to study for beginners, especially in linking the theory with clinical practice.

OBJECTIVE: This study was aimed to compare the teaching effects between case-based learning combined with Rain Classroom teaching and traditional lecture method in the clinical course of complete denture prosthesis for undergraduate interns.

METHODS: In a course called “Problems and treatment strategies of complete denture after wearing”, interns were divided into two groups: one for traditional lecture-based teaching with PowerPoint slideshow (the control group, n = 28); and the other for case-based learning combined with Rain Classroom teaching, which published information before class, discussed specific clinic cases in class and got real-time interns’ feedback via WeChat (the test group, n = 22). Both groups received the same exam and questionnaire survey after class. The Q&A participation of interns in class, theoretical test scores and questionnaire survey responses were used to evaluate the teaching effects. An independent sample t-test and the chi-square test or Fisher’s exact test were used for statistical analysis in this study.

RESULTS: The Q&A participation of interns in the test group was much better than that of the control group. The average score on the theoretical test after class in the test group (72.14 ± 12.24) was significantly higher than that in the control group (61.29 ± 20.12) (P < 0.05). In the test group, 94.54% (21/22) of the interns preferred the new teaching mode.

CONCLUSION: Case-based learning combined with Rain Classroom teaching is helpful to enliven the classroom atmosphere, inspire studying enthusiasm, and achieve a good learning effect in both theory and clinical practice related to complete denture prosthesis.

PMID:35945563 | DOI:10.1186/s12909-022-03678-z

J Anim Sci Biotechnol. 2022 Aug 10;13(1):94. doi: 10.1186/s40104-022-00741-z.

ABSTRACT

BACKGROUND: Carnitine facilitates the flux of long-chain fatty acids for hepatic mitochondrial beta-oxidation, which acts to ameliorate the negative energy balance commonly affecting high-yielding dairy cows. Inflammation triggered by lipopolysaccharide (LPS) load can however pose a challenge to the metabolic integrity via the expression of pro-inflammatory mediators, leading to immune system activation and respective metabolic alterations. The effect of enhanced carnitine availability on hepatic metabolome profiles during an inflammatory challenge has not yet been determined in dairy cows. Herein, Holstein cows were supplemented with 25 g/d rumen-protected carnitine from 42 d prepartum until 126 d postpartum (n = 16) or assigned to the control group with no supplementation during the same period (n = 14). We biopsied the liver of the cows before (100 d postpartum) and after (112 d postpartum) an intravenous injection of 0.5 µg/kg LPS. Liver samples were subjected to a targeted metabolomics analysis using the AbsoluteIDQ p180 Kit (Biocrates Life Sciences AG, Innsbruck, Austria). RESULTS: Multivariate statistical analyses revealed that hepatic metabolome profiles changed in relation to both the carnitine supplementation and the LPS challenge. Comparing the metabolite profiles on 100 d, carnitine increased the concentration of short- and long-chain acyl-carnitines, which may be explained by an enhanced mitochondrial fatty acid shuttle and hence greater energy availability. The LPS injection affected hepatic metabolite profiles only in the carnitine supplemented group, particularly altering the concentration of biogenic amines.

CONCLUSIONS: Our results point to interactions between an acute hepatic inflammatory response and biogenic amine metabolism, depending on energy availability.

PMID:35945561 | DOI:10.1186/s40104-022-00741-z

BMC Med Educ. 2022 Aug 10;22(1):611. doi: 10.1186/s12909-022-03675-2.

ABSTRACT

BACKGROUND: Interprofessional education (IPE) at university level is an essential component of undergraduate healthcare curricula, as well as being a requirement of many associated regulatory bodies. In this study, the perception of pharmacy and medical students’ of remote IPE was evaluated.

METHODS: A series of IPE sessions took place via Zoom and students’ feedback was collected after each session. Both qualitative and quantitative data were collected and analysed.

RESULTS: 72% (23/32) of medical students strongly agreed that the sessions had helped to improve their appreciation of the role of pharmacists, whereas 37% (22/59) of pharmacy students strongly agreed, reporting a median response of ‘somewhat agreeing’, that their appreciation of the role of general practitioners had improved. This difference was found to be statistically significant (p = 0.0143). Amongst students who responded, 55% (53/97) identified remote teaching as their preferred mode of delivery for an IPE session.

CONCLUSIONS: The survey demonstrated that the students valued the development of their prescribing skills as well as the ancillary skills gained, such as communication and teamwork. Remote IPE can be a practical means of improving medical and pharmacy students’ understanding of each other’s professional roles, as well as improving the skills required for prescribing.

PMID:35945560 | DOI:10.1186/s12909-022-03675-2

Arthritis Res Ther. 2022 Aug 9;24(1):190. doi: 10.1186/s13075-022-02883-x.

ABSTRACT

BACKGROUND: We conducted a single-center cohort study of rheumatoid arthritis (RA) patients from 2011 to 2020 to understand their real world treatment and outcomes, especially changes in physical function and quality of life (QOL) in elderly patients, including those aged ≥ 80 years.

METHODS: For RA patients attending our outpatient clinic, we annually recorded tender and swollen joint counts, laboratory findings, therapeutic drugs, and scores from the Japanese Health Assessment Questionnaire and EuroQoL-5 Dimensions questionnaire. We examined changes in treatment and outcomes over time, by age group, in patients enrolled over a 10-year period, from 2011 to 2020.

RESULTS: One thousand eight hundred thirty RA patients were enrolled and data were recorded once a year, and a total of 9299 patient records were evaluated. The average age of patients increased by 3.7 years during the study period; the patients aged rapidly. Intensive pharmacological treatment was more frequent in younger patients. Disease activity, physical function, and QOL showed improvement in all age groups over the study period. Physical function and QOL showed greater changes with aging, compared with disease activity. This may be due to the effects of accumulated RA damage, disability due to aging, and depression.

CONCLUSIONS: Intensive pharmacological treatment contributes to not only control of disease activity but also the improvement of physical activity and QOL, even in elderly patients. Relieving age-related physical impairment and depression may improve the QOL of very elderly RA patients.

PMID:35945556 | DOI:10.1186/s13075-022-02883-x

BMC Endocr Disord. 2022 Aug 9;22(1):199. doi: 10.1186/s12902-022-01116-1.

ABSTRACT

BACKGROUND: Graves’ disease (GD) and papillary thyroid cancer (PTC) can be concomitant. The existence of a link between these entities has long been investigated, but a clear correlation hasn’t been established. We report a case of GD resistant to medical treatment in which surgery revealed unsuspected PTC and we aim to study the prevalence of PTC in Graves’ disease, its clinical characteristics and review of the literature.

CASE PRESENTATION: Report of a 32 yo man who presented with weight loss and was found to be biochemically hyperthyroid. Antibodies were positive. Incremental doses of methimazole provided no improvement in thyroid tests. Hypervascularity and a spongiform nodule were noted on ultrasound. Thyroid uptake and scan showed 70.2% uptake. Thyroidectomy was performed due to inadequate therapeutic response. Pathology revealed PTC with extrathyroidal extension and positive lymph nodes. A retrospective review (2000-2021) and literature review of PTC in GD was performed. Clinical data were reviewed. Statistical analysis was calculated to identify correlations. 243 GD patients had total thyroidectomy at an academic center, 50 (20%) had PTC, 14% were microcarcinomas. 76% of cases were less than 55yo, 82% female, 78% stage 1, PTC diagnosis was incidental in 48%, hyperthyroidism was difficult to treat in 10% and only 2% had recurrence of PTC. There was no correlation between demographic or clinical data.

CONCLUSIONS: Evidence is controversial with some studies showing GD does not affect PTC prognosis. PTC may not be well recognized in GD, pre-operative assessment should consider risk of cancer.

PMID:35945543 | DOI:10.1186/s12902-022-01116-1