Nevin Manimala

Mol Biol Rep. 2022 May 5. doi: 10.1007/s11033-022-07465-3. Online ahead of print.

ABSTRACT

BACKGROUND: Biomarkers, such as microRNAs, are helpful in diagnosing colorectal cancer, regulating disease progression, predicting disease recurrence, and determining therapy success. This research aimed to look at the clinicopathological characteristics of serum miRNA-203a-3p expression in colorectal cancer patients.

METHODS AND RESULTS: This case-control study was conducted on 43 patients with colorectal cancer and 43 healthy individuals. After RNA extraction, cDNA was synthesized. The expression of miR-203a-3p was measured using RT-qPCR. Demographic and histochemical data were extracted from patient documents. SPSS and GraphPad Prism software were used to analyze the data. The expression of miR-203a-3p in CRC patients was 2.39 times lower than in the control group (p < 0.0001). The miR-203a-3p expression was significantly lower in the CRC tumor stages, tumor grades, and lymph node metastasis compared to the control group (p < 0.0001 each). The ROC curves showed that the AUC was 0.73, and the best cut-point based on the Youden index was 0.3954, 0.7105, 0.5087, and 0.4868 for detecting colorectal cancer (p = 0.0002), tumor grade (p = 0.006), tumor stage (p = 0.001), and lymph node metastasis (p = 0.0011) compared to the control group, respectively. The binary logistic regression analysis was performed on the correlation between BMI, smoking, and cancer inheritance with miR-203a-3p in cancer and control groups.

CONCLUSION: This study’s findings revealed that serum miR-203a-3p is a fair non-invasive molecular biomarker for diagnosing and progressing tumor grade, tumor stage, and lymph node metastasis in colorectal cancer. However, further research with higher statistical numbers is needed to strengthen the correlation and be used for diagnostic applications.

PMID:35511316 | DOI:10.1007/s11033-022-07465-3

Graefes Arch Clin Exp Ophthalmol. 2022 May 5. doi: 10.1007/s00417-022-05679-6. Online ahead of print.

ABSTRACT

PURPOSE: PERSEUS-IT (NCT02289924) was a prospective, observational, 2-year study evaluating the effectiveness and treatment patterns of intravitreal aflibercept (IVT-AFL) in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice in Italy.

METHODS: Treatment-naïve patients with nAMD receiving IVT-AFL per routine clinical practice were enrolled. The primary endpoint was mean change in visual acuity (VA; decimals) from baseline to month (M) 12 and M24. Outcomes were evaluated for the overall study population and independently for the 2 treatment cohorts: regular (3 initial monthly doses, ≥ 7 injections by M12, and ≥ 4 injections between M12 and M24) and irregular (any other pattern).

RESULTS: Of 813 patients enrolled, 709 were included in the full analysis set (FAS); VA assessments were available for 342 patients at M12 (FAS1Y, 140 regular and 202 irregular) and 233 patients at M24 (FAS2Y, 37 regular and 196 irregular). In the overall FAS, the mean ± SD change in VA from baseline to M12 and M24 was + 0.09 ± 0.24 and + 0.02 ± 0.25 decimals, and there was a statistically significant difference between the regular and irregular cohorts in both FAS1Y (p = 0.0034) and FAS2Y (p = 0.0222). Ocular treatment-emergent adverse events were reported in 4.1% (n = 33/810 [safety set]) of patients.

CONCLUSION: In PERSEUS-IT, clinically relevant functional and anatomic improvements were observed within the first 12 months of IVT-AFL treatment in routine clinical practice in Italy in patients with treatment-naïve nAMD. These gains were generally maintained across the 2-year study. The safety profile of IVT-AFL was consistent with prior studies.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02289924.

DATE OF REGISTRATION: November 13, 2014.

PMID:35511286 | DOI:10.1007/s00417-022-05679-6

Psychopharmacology (Berl). 2022 May 5. doi: 10.1007/s00213-022-06156-y. Online ahead of print.

ABSTRACT

RATIONALE: Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin’s influence on mood and cognition.

OBJECTIVES: We aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers.

METHODS: Fifty-three healthy subjects were randomly assigned to 7 days of either simvastatin (N = 27) or sucrose-based placebo (N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected.

RESULTS: Compared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task (F_1,51 = 4.99, p = 0.03), but also an increase in anxiety scores (F_1,51 = 5.37, p = 0.02). An exploratory analysis of the females’ subgroup (N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm (F_1,25 = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured.

CONCLUSIONS: We found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies.

TRIAL REGISTRATION: Clinicaltrials.gov: NCT04652089.

PMID:35511258 | DOI:10.1007/s00213-022-06156-y

Int Urogynecol J. 2022 May 5. doi: 10.1007/s00192-022-05209-2. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse is among the most common gynecologic problems worldwide. It greatly influences women’s quality of life. However, research regarding the effect of pelvic organ prolapse on quality of life is limited in our study area.

METHODS: An institutional-based study design among women with the diagnosis of pelvic organ prolapse at Felege Hiwot Comprehensive Specialized Hospital was employed from May to July 2018. Interviewer-administered questionnaire and Prolapse Quality of Life assessment tool were used to collect data. Gynecologic speculum examination was done to collect objective data. Data were entered into Epi info version 7 and then exported in to SPSS, version 20.0, for analysis. Descriptive statistics and logistic regression were used. All the statistical tests were significant at P < 0.05.

RESULTS: The average prolapse quality of life score was 48.35 ± 22.75 SD. The physical limitation (score: 69.83 ± 28.77 SD) and general health perception (score: 67.39 ± 20.26 SD) domains were the most affected life domains. Younger age (AOR = 3.02 [95% CI: 1.22-7.45]), being illiterate (AOR = 3.52 [95% CI: 1.12-11.10]), and having stage IV POP (AOR = 2.84 [95% CI: 1.16-7.00]) were associated with lower quality of life.

CONCLUSIONS: The QOL score showed huge variability among the study participants. The physical limitation and general health perception domains were most affected. Being illiterate, being < 35 years old, and having stage IV pelvic organ prolapse were the factors associated with lower quality of life.

PMID:35511251 | DOI:10.1007/s00192-022-05209-2

Anal Bioanal Chem. 2022 May 5. doi: 10.1007/s00216-022-04064-w. Online ahead of print.

ABSTRACT

The stability of psychotropic substances representing various drug groups important from the perspective of forensic chemistry, including benzodiazepines, antidepressants, carbamazepine, cocaine, and their selected metabolites, was investigated for 1 month in two alternative biological matrices, vitreous humor and liver homogenate. Three different thermal storage conditions (-20, 4, and 20 °C) were tested. Liquid chromatography-mass spectrometry (LC-MS) analysis was preceded by an effective solid-phase microextraction (SPME) procedure. The results were statistically analyzed using one-way ANOVA to find significant concentration variations over time. The results obtained allowed for dividing the analytes into four groups: stable under all tested conditions, only at -20 and 4 °C, only at 20 °C, and overall unstable. Nordiazepam, venlafaxine, and cocaine and its metabolites turned out to be the most unstable substances, while fluoxetine showed the highest storage stability in both matrices. The SPME/LC-MS method was comprehensively evaluated according to the principles of white analytical chemistry (WAC), which reconcile the greenness and functionality of the method. A close to 100% whiteness score proves its sustainability and suitability for the intended application.

PMID:35511247 | DOI:10.1007/s00216-022-04064-w

JMIR Serious Games. 2022 May 5;10(2):e34222. doi: 10.2196/34222.

ABSTRACT

BACKGROUND: People with severe mental illness (SMI) face discriminatory situations because of prejudice toward them, even among health care personnel. Escape rooms can be a novel educational strategy for learning about and empathizing with SMI, thus reducing stigma among health care students.

OBJECTIVE: This study aimed to examine the effect of the Without Memories escape room on nursing students’ stigma against SMI.

METHODS: A pre- and postintervention study was conducted with a control group and an experimental group. A total of 306 students from 2 Andalusian universities participated in the study. Data were collected through a pre-post study questionnaire, consisting of an adapted version of the Attributional Style Questionnaire and a questionnaire on motivation for cooperative playful learning strategies. The control group carried out an escape room scenario without sensitizing content, whereas the experimental group carried out an escape room scenario on SMI, with both escape rooms being carried out in a 1-hour session of subjects related to mental health. To answer the research questions, a 2-way analysis of variance with repeated measures, a linear regression, and a 2-way analysis of variance were performed.

RESULTS: After the intervention, a significant reduction (P<.001) was observed in the experimental group in stigmatizing attitudes compared with the control group, in which no statistically significant changes (P>.05) were observed. In contrast, the linear regression (t₁₉₅=-22.15; P<.001) showed that there was an inverse relationship between flow and the level of reduced stigma. When controlling for having or not having a close relative, the intervention was also shown to be effective (P<.001) in reducing the stigma displayed, both for people with affected and unaffected relatives.

CONCLUSIONS: Our findings suggest that the Without Memories escape room can be used as an effective tool to educate and raise awareness about stigmatizing attitudes toward SMI in university students studying health care. Future testing of the effectiveness of educational escape rooms should be designed with new programs through playful strategies of longer duration to evaluate whether they can achieve a greater impact on motivation, acquisition of knowledge, and awareness. In addition, the feasibility of implementing the Without Memories escape room in other careers related to health and community should be investigated.

PMID:35511232 | DOI:10.2196/34222

J Med Internet Res. 2022 May 5;24(5):e34302. doi: 10.2196/34302.

ABSTRACT

BACKGROUND: Virtual communities of practice (VCoPs) have been used to support innovation and quality in clinical care. The drug mifepristone was introduced in Canada in 2017 for medical abortion. We created a VCoP to support implementation of mifepristone abortion practice across Canada.

OBJECTIVE: The aim of this study was to describe the development and use of the Canadian Abortion Providers Support-Communauté de pratique canadienne sur l’avortement (CAPS-CPCA) VCoP and explore physicians’ experience with CAPS-CPCA and their views on its value in supporting implementation.

METHODS: This was a mixed methods intrinsic case study of Canadian health care providers’ use and physicians’ perceptions of the CAPS-CPCA VCoP during the first 2 years of a novel practice. We sampled both physicians who joined the CAPS-CPCA VCoP and those who were interested in providing the novel practice but did not join the VCoP. We designed the VCoP features to address known and discovered barriers to implementation of medication abortion in primary care. Our secure web-based platform allowed asynchronous access to information, practice resources, clinical support, discussion forums, and email notices. We collected data from the platform and through surveys of physician members as well as interviews with physician members and nonmembers. We analyzed descriptive statistics for website metrics, physicians’ characteristics and practices, and their use of the VCoP. We used qualitative methods to explore the physicians’ experiences and perceptions of the VCoP.

RESULTS: From January 1, 2017, to June 30, 2019, a total of 430 physicians representing all provinces and territories in Canada joined the VCoP and 222 (51.6%) completed a baseline survey. Of these 222 respondents, 156 (70.3%) were family physicians, 170 (80.2%) were women, and 78 (35.1%) had no prior abortion experience. In a survey conducted 12 months after baseline, 77.9% (120/154) of the respondents stated that they had provided mifepristone abortion and 33.9% (43/127) said the VCoP had been important or very important. Logging in to the site was burdensome for some, but members valued downloadable resources such as patient information sheets, consent forms, and clinical checklists. They found email announcements helpful for keeping up to date with changing regulations. Few asked clinical questions to the VCoP experts, but physicians felt that this feature was important for isolated or rural providers. Information collected through member polls about health system barriers to implementation was used in the project’s knowledge translation activities with policy makers to mitigate these barriers.

CONCLUSIONS: A VCoP developed to address known and discovered barriers to uptake of a novel medication abortion method engaged physicians from across Canada and supported some, including those with no prior abortion experience, to implement this practice.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-028443.

PMID:35511226 | DOI:10.2196/34302

Nicotine Tob Res. 2022 May 2:ntac067. doi: 10.1093/ntr/ntac067. Online ahead of print.

ABSTRACT

INTRODUCTION: Despite high levels of illicit trade in the tobacco market, the South African government banned the sale of tobacco products in March 2020 as part of its COVID-19 response. The ban lasted five months. We assess how the ban affected the cigarette market for a sample of smokers by comparing the price, consumption, and competitive landscapes before (March), during (May and June), and after (September) the ban.

METHODS: We conducted three online surveys of cigarette smokers, asking about smoking behavior before, during, and after the ban. We use descriptive statistics and OLS regressions to estimate the impact of the ban on the South African cigarette market, focusing on the price of cigarettes.

RESULTS: Most smokers continued smoking despite the sales ban. During the ban, prices increased by over 240%. Purchases shifted away from the normally dominant brands of the multinational tobacco companies to local/regional producers. The covariates of price changed substantially during the sales ban, the most pronounced being inter-provincial effects. After the ban, the market shifted back to its preban state, with an overall increase in price of 3.6%.

CONCLUSIONS: Cigarette sales continued despite the sales ban, further entrenching an already large illicit market. Had the government substantially increased the excise tax, rather than banned the sale of tobacco products, it would have achieved a similar public health outcome, received more revenue, and presumably not further entrenched the illicit market.

IMPLICATIONS: South Africa temporarily banned the sale of tobacco as part of its COVID-19 response. Despite the ban, the sale of cigarettes did not cease; rather, it caused major disruption to the cigarette market. The ban inadvertently benefited manufacturers who were previously disproportionately involved in illicit activities; these manufacturers increased their market share even after the ban was lifted. The ban may have further entrenched South Africa’s already large illicit market. Our results show that there are unintended consequences associated with a temporary ban on the sale of cigarettes.

PMID:35511202 | DOI:10.1093/ntr/ntac067

Brain. 2022 May 2:awab432. doi: 10.1093/brain/awab432. Online ahead of print.

ABSTRACT

Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cerebral small vessel disease derived from its most common MRI features: white matter hyperintensities and lacunes. Seventeen population-based cohorts of older persons with MRI measurements and genome-wide genotyping (n = 41 326), whole-exome sequencing (n = 15 965), or exome chip (n = 5249) data contributed 13 776 and 7079 extreme small vessel disease samples for the genome-wide association study and whole-exome association study, respectively. The genome-wide association study identified significant association of common variants in 11 loci with extreme small vessel disease, of which the chr12q24.11 locus was not previously reported to be associated with any MRI marker of cerebral small vessel disease. The whole-exome association study identified significant associations of extreme small vessel disease with common variants in the 5′ UTR region of EFEMP1 (chr2p16.1) and one probably damaging common missense variant in TRIM47 (chr17q25.1). Mendelian randomization supports the causal association of extensive small vessel disease severity with increased risk of stroke and Alzheimer’s disease. Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. We observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology. Overall, our comprehensive gene-mapping study and preliminary functional evaluation suggests a putative role of TRIM47 in the pathophysiology of cerebral small vessel disease, making it an important candidate for extensive in vivo explorations and future translational work.

PMID:35511193 | DOI:10.1093/brain/awab432

JAMA Netw Open. 2022 May 2;5(5):e2210480. doi: 10.1001/jamanetworkopen.2022.10480.

ABSTRACT

IMPORTANCE: Implemented in 2012, the Healthy, Hunger-Free Kids Act of 2010 (HHFKA) increased nutritional requirements of the National School Lunch Program (NSLP) to reverse the potential role of the NSLP in childhood obesity.

OBJECTIVE: To evaluate whether associations between the free or reduced-price NSLP and body mass growth differed after implementation of the HHFKA.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2 nationally representative cohorts of US kindergarteners sampled in 1998 to 1999 and 2010 to 2011 and followed up for 6 years, through grade 5, in the Early Childhood Longitudinal Study Kindergarten Class of 1998-1999 (ECLS-K:1999, in 2003-2004) and Kindergarten Class of 2010-2011 (ECLS-K:2011, in 2015-2016). In total, 5958 children were selected for analysis from low-income families eligible for the free or reduced-price NSLP (household income <185% of the federal poverty level) who attended public schools and had no missing data on free or reduced-price NSLP participation or on body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) at kindergarten or grades 1 and 5. Data were analyzed from January 1 to September 7, 2021.

EXPOSURES: Cross-cohort comparison of before vs after implementation of the HHFKA for free or reduced-price NSLP participation at kindergarten and grades 1 and 5.

MAIN OUTCOMES AND MEASURES: Body mass index difference (BMID) from obesity threshold was the difference in BMI units from the age- and sex-specific obesity thresholds (95th percentile) and is sensitive to change at high BMI. Multigroup models by cohort included weights to balance the distribution of the 2 cohorts across a wide range of covariates. A Wald test was used to assess whether associations differed between the cohorts.

RESULTS: In the final analysis, 3388 children in ECLS-K:1999 (1696 girls [50.1%]; mean [SD] age at baseline, 74.6 [4.3] months) and 2570 children in ECLS-K:2011 (1348 males [52.5%]; mean [SD] age at baseline, 73.6 [4.2] months) were included. The best fitting model for BMID change by free or reduced-price NSLP participation across the cohorts included fixed and time-varying associations. Before HHFKA implementation, grade 5 free or reduced-price NSLP participants had higher BMID, adjusted for their prior BMID trajectory, than nonparticipants (β = 0.54; 95% CI, 0.27-0.81). After HHFKA implementation, this association was attenuated (β = -0.07; 95% CI, -0.58 to 0.45), and grade 5 associations were different across cohorts (χ21 = 4.29, P = .04).

CONCLUSIONS AND RELEVANCE: In this cohort study using cross-cohort comparisons, children from low-income families who participated in the free or reduced-price NSLP had a higher likelihood of progression to high BMI that was no longer observed after HHFKA implementation. This finding suggests that the HHFKA may have attenuated the previous association of the NSLP with child obesity disparities.

PMID:35511177 | DOI:10.1001/jamanetworkopen.2022.10480