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Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults

Immun Ageing. 2023 Jan 17;20(1):4. doi: 10.1186/s12979-023-00327-x.

ABSTRACT

BACKGROUND: Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses.

METHODS: We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used linear regression with clustered error for antibody titers over multiple timepoints with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used linear regression models with clinical predictors and cellular memory phenotype variables.

RESULTS: Participants (n = 15) had median age of 90 years and mild, moderate, or severe frailty scores (n = 3, 7, or 5 respectively). Over the study time course, anti-spike antibody titers were 10-fold higher in individuals with lower frailty status (p = 0.001 and p = 0.005, unadjusted and adjusted for prior COVID-19 infection). Following the booster, titers to spike protein improved regardless of COVID-19 infection or degree of frailty (p = 0.82 and p = 0.29, respectively). Antibody avidity significantly declined over 6 months in all participants following 2 vaccine doses (p < 0.001), which was further impaired with higher frailty (p = 0.001). Notably, avidity increased to peak levels after the booster (p < 0.001). Overall antibody response was inversely correlated with a phenotype of immune-senescent T cells, CD8 + CD28- TEMRA cells (p = 0.036, adjusted for COVID-19 infection). Furthermore, there was increased detection of CD8 + CD28- TEMRA cells in individuals with greater frailty (p = 0.056, adjusted for COVID-19).

CONCLUSIONS: We evaluated the immune responses to the Moderna COVID-19 mRNA vaccine in frail older adults in a retirement community. A higher degree of frailty was associated with diminished antibody quantity and quality. However, a booster vaccine dose at 6 months overcame these effects. Frailty was associated with an increased immune-senescence phenotype that may contribute to the observed changes in the vaccine response. While the strength of our conclusions was limited by a small cohort, these results are important for guiding further investigation of vaccine responses in frail older adults.

PMID:36650551 | DOI:10.1186/s12979-023-00327-x

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FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma

J Transl Med. 2023 Jan 17;21(1):32. doi: 10.1186/s12967-023-03874-5.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) and prostate cancer (PCa) are among the most prevalent malignant tumors worldwide. There is now a comprehensive understanding of metabolic reprogramming as a hallmark of cancer. Fatty acid synthase (FASN) is a key regulator of the lipid metabolic network, providing energy to favor tumor proliferation and development. Whereas the biological role of FASN is known, its response and sensitivity to inhibition have not yet been fully established in these two cancer settings.

METHODS: To evaluate the association between FASN expression, methylation, prognosis, and mutational profile in PDAC and PCa, we interrogated public databases and surveyed online platforms using TCGA data. The STRING database was used to investigate FASN interactors, and the Gene Set Enrichment Analysis platform Reactome database was used to perform an enrichment analysis using data from RNA sequencing public databases of PDAC and PCa. In vitro models using PDAC and PCa cell lines were used to corroborate the expression of FASN, as shown by Western blot, and the effects of FASN inhibition on cell proliferation/cell cycle progression and mitochondrial respiration were investigated with MTT, colony formation assay, cell cycle analysis and MitoStress Test.

RESULTS: The expression of FASN was not modulated in PDAC compared to normal pancreatic tissues, while it was overexpressed in PCa, which also displayed a different level of promoter methylation. Based on tumor grade, FASN expression decreased in advanced stages of PDAC, but increased in PCa. A low incidence of FASN mutations was found for both tumors. FASN was overexpressed in PCa, despite not reaching statistical significance, and was associated with a worse prognosis than in PDAC. The biological role of FASN interactors correlated with lipid metabolism, and GSEA indicated that lipid-mediated mitochondrial respiration was enriched in PCa. Following validation of FASN overexpression in PCa compared to PDAC in vitro, we tested TVB-2640 as a FASN inhibitor. PCa proliferation arrest was modulated by FASN inhibition in a dose- and time-dependent manner, whereas PDAC proliferation was not altered. In line with this finding, mitochondrial respiration was found to be more affected in PCa than in PDAC. FASN inhibition interfered with metabolic signaling causing lipid accumulation and affecting cell viability with an impact on the replicative processes.

CONCLUSIONS: FASN exhibited differential expression patterns in PDAC and PCa, suggesting a different evolution during cancer progression. This was corroborated by the fact that both tumors responded differently to FASN inhibition in terms of proliferative potential and mitochondrial respiration, indicating that its use should reflect context specificity.

PMID:36650542 | DOI:10.1186/s12967-023-03874-5

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Evaluation of career planning group counseling and its effectiveness for intern male nursing students

BMC Med Educ. 2023 Jan 17;23(1):34. doi: 10.1186/s12909-022-03981-9.

ABSTRACT

OBJECTIVE: To investigate the influence of group counselling on the career planning and career maturity of male nursing students.

METHOD: Sixty male nursing students were randomly selected from a specific-level first-class hospital in Hunan Province from July to August 2020 by using the convenience sampling method and were subsequently divided into the control group and the experimental group using the random number table method. The control group received routine pre-job training, including aspects concerning the hospital profile, nurse etiquette, nursing core systems, professional ethics, nursing emergency treatment and career prospects and planning. In the experimental group, career planning group counselling was added after the regular pre-service training (once a week) with each session lasting 2 h for a total of six training sessions. At six weeks and three months after the intervention, the career status evaluation scale and the college students’ career maturity scale were used to compare the career planning and career maturity status of the two groups of male nursing students.

RESULTS: After six weeks and three months of intervention, all the dimensions and total scores of both the career status evaluation scale and the career maturity scale in the experimental group were superior to those in the control group with statistically significant differences (all P < 0.05). The repeated measures of variance analysis indicated that the differences in the total score for career planning and the four dimensions in terms of intergroup effect, time effect and interaction effect between the two groups were statistically significant (P < 0.05). The intergroup effect, time effect and interaction effect of the total score for vocational maturity, career goal, career confidence, career value, career freedom and career reference of the two groups were statistically significant (P < 0.05), while the time effect of the relative dependency dimension was also statistically significant (P < 0.05).

CONCLUSION: Group counselling can significantly improve the career planning and career maturity status of male nursing students and has a certain long-term effect.

PMID:36650532 | DOI:10.1186/s12909-022-03981-9

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Clinical outcomes of a novel porcine small intestinal submucosa patch for full-thickness hand skin defects: a retrospective investigation

J Orthop Surg Res. 2023 Jan 17;18(1):50. doi: 10.1186/s13018-023-03531-z.

ABSTRACT

OBJECTIVE: To investigate the clinical outcomes of a novel soft tissue repair patch (porcine small intestinal submucosa patch, SIS patch) in the treatment of full-thickness hand skin defects.

METHODS: From January 2017 to July 2019, 80 patients with hand soft tissue defects, who met the inclusion criteria, were retrospectively reviewed and divided into two groups. After debridement, patients in group A were treated with the novel SIS patch to cover the wound, and patients in group B were treated with autologous skin graft. The dimensions of skin defect area and healing outcome were evaluated and recorded. Scar assessment was carried out using Scar Cosmesis Assessment and Rating Scale (SCAR scale) at the last follow-up postoperation, and the recovery of wound sensation was assessed at the same time using British Medical Research Council (BMRC) grading of sensorimotor recovery. All the data were collected and statistically analyzed.

RESULTS: A total of 80 patients were enrolled in the study with 40 patients in each group. Four patients in group A and 5 patients in group B were excluded due to wound infection and lost to follow-up. There were 36 patients in group A and 35 patients in group B finally got follow-up postoperation with mean interval of 12.75 ± 5.61 months in group A and 14.11 ± 5.42 months in group B. The dimensions of skin defect area in group A ranged from 7.5 to 87.5 cm2 (mean 25.97 ± 18.66 cm2) and in group B ranged from 7.5 to 86.25 cm2 (mean 33.61 ± 19.27 cm2) which have no significant difference (P > 0.05). SCAR scale results of group A and group B were 10.98 ± 0.33 and 9.49 ± 0.35, respectively, and the difference was statistically significant (P < 0.05). BMRC grading results showed 6 cases of S4, 11 cases of S3+, 5 cases of S3, 6 cases of S2, 6 cases of S1 and 2 cases of S0 in group A, and 8 cases of S4, 10 cases of S3+, 7 cases of S3, 4 cases of S2, 5 cases of S1, and 1 case of S0 in group B, which had no significant difference between them (P > 0.05).

CONCLUSIONS: The novel SIS patch is an applicable biological material in the treatment of hand skin defect, which could achieve a better cosmetic appearance of the newborn skin tissue.

PMID:36650521 | DOI:10.1186/s13018-023-03531-z

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Prevalence of teenage pregnancy and its associated factors in high fertility sub-Saharan Africa countries: a multilevel analysis

BMC Womens Health. 2023 Jan 17;23(1):23. doi: 10.1186/s12905-023-02169-7.

ABSTRACT

BACKGROUND: Teenage pregnancies are persistently high among adolescent women in high fertility countries in sub-Saharan Africa. It has been attributed to the high unmet need for family planning in this population. The aim of this study was to determine the prevalence and factors associated with teenage pregnancy in high fertility countries in sub-Saharan Africa.

METHODS: Data for this study was obtained from the most recent Demographic and Health Surveys. A total weighted sample of 33,391 adolescent girls who had ever had sexual contact were included. A multilevel mixed-effect binary logistic regression model was fitted to identify the significant associated factors for teenage pregnancy. Finally, the Adjusted Odds Ratio (AOR) with a 95% confidence interval was used to declare as statistically significant.

RESULTS: The overall teenage pregnancy in sub-Saharan Africa high frtility countries was 24.88% (95% CI, 24.42, 25.35). Educational status; no formal education (AOR = 1.39, 95% CI, 1.23, 1.56) and primary education (AOR = 1.45, 95% CI, 1.30, 1.62), not working (AOR = 1.32, 95% CI, 1.21, 1.45), being married (AOR = 67.88, 95% CI, 61.33, 75.12), poor (AOR = 1.47, 95% CI, 1.32, 1.65) and middle wealth quantile (AOR = 1.21, 95% CI, 1.07, 1.35), knowledge about contracptives (AOR = 2.45, 95% CI, 2.19, 2.74), unmet need for family planning (AOR = 2.42, 95% CI, 2.14, 2.74), Angola (AOR = 9.59, 95% CI, 7.82, 11.77), Chad (AOR = 3.05, 95% CI, 2.49, 3.74), DR.Congo (AOR = 3.77, 95% CI, 3.06, 4.65), and Mali (AOR = 1.84, 95% CI, 1.47, 2.28) were factors significantly associated with teenage pregnancy.

CONCLUSIONS: This study found that teenage pregnancy remains a common public health problem in the study areas. Level of education, marital status, occupation, wealth index, unmet need for family planning, knowledge about contraceptives, and country were significantly associated with teenage pregnancy. Hence, for sustainable development goal 3 to be realized by 2030, there must be investment in policy implementation and evaluation, as well as engagement with stakeholders in adolescents’ sexual and reproductive health.

PMID:36650514 | DOI:10.1186/s12905-023-02169-7

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Potential factors that can affect the performance of undergraduate pharmacy research students: a descriptive study

BMC Med Educ. 2023 Jan 17;23(1):32. doi: 10.1186/s12909-023-04018-5.

ABSTRACT

OBJECTIVE: This descriptive study aimed to examine whether student past coursework performance, student or research supervisor characteristics, and the type of research project are related to the overall academic performance of a pharmacy student completing an honours research program.

METHODS: Data on undergraduate honours students who completed a Bachelor of Pharmacy degree at The University of Sydney, Sydney, Australia, between Jan 2015 and Dec 2020 was collected. This included socio-demographic characteristics, type of project undertaken, and academic outputs. Data was also collected on each supervisor’s academic role, level of experience, research area, and where they completed their PhD. Descriptive statistics were used to describe the study cohort and correlation analysis and unpaired t-tail analyses were conducted using SPSS software.

RESULTS: This five year study included 130 students of which 67% were female and 60% were domestic students. Each student was supervised by one of 48 individual academics who were a mix of early- (31%), mid-career (29%), and experienced researchers (40%) for pharmaceutical science (50%), clinical (45%), and education (5%) projects. Just less than half (49%) of students published one peer-reviewed journal article. Female students outperformed male students (p = 0.031) with female students also twice as likely (15%) to receive a university medal eligible mark compared with male students (7.0%). Similarly, domestic students were twice as likely (15%) to receive a university medal eligible mark when compared with international students (7.7%). Students who undertook a pharmaceutical science-based project outperformed education-based project students (p = 0.0235). Students who had published at least one peer-reviewed journal article outperformed those who had not published (p = 0.0014).

CONCLUSION: Factors that affected honours performance were student gender, residential status, type of project undertaken, and whether a student had published a peer-reviewed journal article.

PMID:36650513 | DOI:10.1186/s12909-023-04018-5

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Prediction of contraceptive discontinuation among reproductive-age women in Ethiopia using Ethiopian Demographic and Health Survey 2016 Dataset: A Machine Learning Approach

BMC Med Inform Decis Mak. 2023 Jan 17;23(1):9. doi: 10.1186/s12911-023-02102-w.

ABSTRACT

BACKGROUND: Globally, 38% of contraceptive users discontinue the use of a method within the first twelve months. In Ethiopia, about 35% of contraceptive users also discontinue within twelve months. Discontinuation reduces contraceptive coverage, family planning program effectiveness and contributes to undesired fertility. Hence understanding potential predictors of contraceptive discontinuation is crucial to reducing its undesired outcomes. Predicting the risk of discontinuing contraceptives is also used as an early-warning system to notify family planning programs. Thus, this study could enable to predict and determine the predictors for contraceptive discontinuation in Ethiopia.

METHODOLOGY: Secondary data analysis was done on the 2016 Ethiopian Demographic and Health Survey. Eight machine learning algorithms were employed on a total sample of 5885 women and evaluated using performance metrics to predict and identify important predictors of discontinuation through python software. Feature importance method was used to select top predictors of contraceptive discontinuation. Finally, association rule mining was applied to discover the relationship between contraceptive discontinuation and its top predictors by using R statistical software.

RESULT: Random forest was the best predictive model with 68% accuracy which identified the top predictors of contraceptive discontinuation. Association rule mining identified women’s age, women’s education level, family size, husband’s desire for children, husband’s education level, and women’s fertility preference as predictors most frequently associated with contraceptive discontinuation.

CONCLUSION: Results have shown that machine learning algorithms can accurately predict the discontinuation status of contraceptives, making them potentially valuable as decision-support tools for the relevant stakeholders. Through association rule mining analysis of a large dataset, our findings also revealed previously unknown patterns and relationships between contraceptive discontinuation and numerous predictors.

PMID:36650511 | DOI:10.1186/s12911-023-02102-w

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Is the anterior cervical dynamic plate fixation better than the anterior static plate fixation: a retrospective review with over 5 years follow-up

BMC Musculoskelet Disord. 2023 Jan 18;24(1):37. doi: 10.1186/s12891-023-06156-9.

ABSTRACT

BACKGROUND: To compare the clinical and radiologic outcomes after anterior cervical dynamic or static plate fixation for short segment cervical degenerative disc diseases (DDD) for more than 5 years.

METHODS: Sixty-four patients who underwent anterior cervical one level discectomy or corpectomy with an anterior cervical plate system were followed for an average of 6.8 years for clinical and radiographic outcomes. Among the sixty-four patients, thirty-eight patients were fixed with a static plate (ORION and CSLP plate system) and the other twenty-six patients were fixed with a dynamic plate (ABC plate). Radiographic data were collected included the global sagittal alignment of the cervical spine (C2-C7), the local height and angle of the operated level pre-operatively, postoperatively and at last follow-up. A clinical assessment was performed at pre-operatively, three months postoperatively and final follow-up using the Japanese Orthopedic Association (JOA) /Visual Analogue Score(VAS)/ Neck Disablility Index(NDI) scoring system.

RESULTS: The mean follow-up time was 6.8 years. At final review, there were two cases of suspicious pseudarthrosis which were from ABC plate fixation group while the other cases all gained solid fusion. The height of fusion segment gained significantly improvement for both dynamic and static plate group post-operation, and all groups demonstrated a significant loss in height postoperatively. Generally, for the one level ACDF group, the height decrease was 0.5 mm for static plate and 1.6 mm for dynamic group which was significantly different(p < 0.05). And for one level ACCF group, this type of difference was not seen in which decreasing was 1.7 mm for static group and 1.8 mm for dynamic group. Segmental lordosis of the fusion segments was increased significantly both post-operation and final follow-up than before-operation for both one and two segments fusion. Global cervical lordosis from C2-C7 was increased in the early postoperative period in all groups, and at final follow-up the total lordosis was still getting better compared with early postoperative period, but this increase was not statistically significant. Clinical assessment of JOA/NDI showed that there was significantly improvement 3-month post-operation compared with pre-operation, and the score could get a slight further improvement at the final follow-up.

CONCLUSION: Our study demonstrated a statistically similar fusion rate between dynamic and static cervical plate fixation. However, the height gained with static plate fixation for single segment disease was maintained better than with dynamic plate fixation and there was no difference between JOA outcome scores between groups. Despite the reported improved biomechanics of dynamic plate fixation, further research needs to be done to show the clinical advantage of dynamic plate fixation.

PMID:36650488 | DOI:10.1186/s12891-023-06156-9

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Dry needling on latent and active myofascial trigger points versus oral diclofenac in patients with knee osteoarthritis: a randomized controlled trial

BMC Musculoskelet Disord. 2023 Jan 18;24(1):36. doi: 10.1186/s12891-022-06116-9.

ABSTRACT

BACKGROUND: Latent and active myofascial trigger points (MTrPs) in knee-associated muscles may play a key role in pain management among patients with knee osteoarthritis (KOA). The aim of this study was to investigate the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with KOA.

METHODS: This randomized, single-blinded, clinical trial was carried out for 6 weeks of treatment and 6-month follow-up. A total of 98 patients met the entry criteria and were randomly assigned to the dry needling latent and active myofascial trigger point (MTrPs) with the stretching group or the oral diclofenacwith the stretching group. Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up.

RESULTS: A total of 42 patients in the dry needling group (DNG) and 35 patients in the diclofenac group (DG), respectively, completed the study, and there was no significant difference in the general data between the two groups. After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the DNG showed a significantly better result than the DG. Especially in the results of the 6-month follow-up, the DNG showed much better results than the DG.

CONCLUSIONS: Dry needling on latent and active MTrPs combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by KOA. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months.

TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ) in 17/11/2017 with the following code: ChiCTR-INR-17013432.

PMID:36650486 | DOI:10.1186/s12891-022-06116-9

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Egg consumption reduces the risk of depressive symptoms in the elderly: findings from a 6-year cohort study

BMC Psychiatry. 2023 Jan 17;23(1):44. doi: 10.1186/s12888-023-04540-2.

ABSTRACT

BACKGROUND: Accumulating evidence showed that dietary habits might modify the risk of depression. This study aimed to evaluate the longitudinal association of egg consumption with depressive symptoms in the Chinese elderly.

METHODS: We analyzed the data from Zhejiang Ageing and Health Cohort Study including 8289 participants. The Patient Health Questionnaire-9 scale (PHQ-9) was used to assess depressive symptoms at baseline and three waves of follow-up (2015, 2016, and 2019-2020). A PHQ-9 cut-off score ≥ 5 was used to define depressive symptoms. The participants with depressive symptoms at baseline were excluded. Egg consumption was evaluated through the diet habits section of the baseline questionnaire. Self-reported egg consumption was measured as the number of eggs per week and categorized into three categories. Log-binomial regression models with Generalized Estimating Equations were utilized to evaluate the association of egg consumption with depressive symptoms and estimate relative risks (RRs).

RESULTS: The mean age of included participants was 68.6 years. After 6 years of follow-up, 1385 (16.7%) participants were indicated with depressive symptoms by PHQ-9 at least once. Compared with non-consumers or less-than-weekly consumers, participants consuming < 3 eggs/week and ≥ 3 eggs/week had 30% (RR = 0.70, 95%CI 0.62-0.80) and 38% (RR = 0.62, 95%CI 0.54-0.71) lower risks of depressive symptoms, respectively. A linear association was confirmed (P for trend < 0.01), and each egg increment per week was associated with a 4% lower risk of depressive symptoms (RR = 0.96, 95%CI 0.93-0.99). Sensitivity analyses yielded consistent results to the main analyses.

CONCLUSIONS: Egg consumption is prospectively related to a lower risk of depressive symptoms in the Chinese elderly. More prospective studies are needed to verify the association.

PMID:36650485 | DOI:10.1186/s12888-023-04540-2