Nevin Manimala

BMC Vet Res. 2022 Dec 23;18(1):445. doi: 10.1186/s12917-022-03552-6.

ABSTRACT

BACKGROUND: Equine intestinal epithelial stem cells (ISCs) serve as potential targets to treat horses with severe intestinal injury. The ability to isolate and store ISCs from intestinal biopsies creates an opportunity for both in vitro experiments to study ISC dynamics in a variety of intestinal diseases, and, in the future, utilize these cells as a possible therapy. If biopsies could be successfully stored prior to processing for ISCs, this would increase the availability of sample repositories for future experimental and therapeutic use. However, delayed culture of equine ISCs following prolonged sample storage has not been described. The objective of this study was to describe the isolation and culture of equine ISCs following delayed tissue storage. Small intestinal full thickness biopsies were collected post euthanasia. Fresh tissue was immediately processed or stored at 4 °C for 24, 48 and 72 h (H) before processing. Intestinal stem cells (crypts) were dissociated and cultured. Size, growth efficiency and proliferation potential were compared between resultant enteroids (“mini-guts”) derived from each storage timepoint. In a separate study, growth efficiency of cryopreserved crypts was compared to cryopreserved enteroid fragments to investigate prolonged storage techniques.

RESULTS: Intestinal crypts were successfully isolated and cultured from all timepoints. At 72H post initial collection, the intestine was friable with epithelial sloughing; resultant dissociation yielded more partial crypts. Enteroids grown from crypts isolated at 72H were smaller with less proliferative potential (bud units, (median 6.5, 3.75-14.25)) than control (median 25, 15-28, p < 0.0001). No statistical differences were noted from tissues stored for 24H compared to control. Following cryopreservation, growth efficiency improved when cells were stored as enteroid fragments (median 81.6%, 66.2-109) compared to crypts (median 21.2%, 20-21.5, p = 0.01). The main limitations included a small sample size and lack of additional functional assays on enteroids.

CONCLUSIONS: Equine ISCs can be isolated and cultured after prolonged tissue storage. Resultant enteroids had minimal differences even after 24-48H of whole tissue storage. This suggests that ISCs could be isolated for several days from samples properly stored after procedures, including surgery or necropsy, and used to create ISC repositories for study or therapy of equine intestinal diseases.

PMID:36564773 | DOI:10.1186/s12917-022-03552-6

BMC Med Educ. 2022 Dec 23;22(1):891. doi: 10.1186/s12909-022-03969-5.

ABSTRACT

BACKGROUND: Supervisors play a key part as role models and supporting the learning during residents’ post-graduate medical education, but sometimes lack sufficient pedagogic training and are challenged by high demands in today’s healthcare. The aim of this study was to describe the strengths and areas for improvement identified in the supervision process by residents and supervisors in post-graduate medical education.

METHODS: This study included supervisors and residents working at departments and health centres who have used a web-based questionnaire, as a part of the Evaluation and Feedback For Effective Clinical Teaching (EFFECT) model, during the period 2016-2019. Descriptive statistics and content analysis were used to analyse ratings and comments to describe strengths and areas for improvement in the supervision process.

RESULTS: The study included 287 resident evaluations of supervisors and 78 self-evaluations by supervisors. The supervisor as a role model, being available, and, giving personal support, were the three most important strengths identified by the residents and supervisors. Residents in primary care also identified the role modelling of general practice competence as a strength, whereas residents and supervisors in hospital departments addressed supervisors as energetic and showing work was fun. The area with the need of most improvement was, Giving and receiving feedback.

CONCLUSIONS: To be able to give feedback, residents and supervisors, needed to see each other in work, and the learning environment had to offer time and space to pedagogical processes, like feedback, to improve the learning environment.

PMID:36564770 | DOI:10.1186/s12909-022-03969-5

BMC Oral Health. 2022 Dec 23;22(1):635. doi: 10.1186/s12903-022-02674-5.

ABSTRACT

BACKGROUND: Evaluating the effect of different surface treatment methods on the micro-tensile bond strength (µTBS) of two different resin-matrix computer-aided design/computer-aided manufacturing (CAD/CAM) ceramics (RMCs).

METHODS: A standardized inlay preparations were performed on 100 intact maxillary premolars. According to the type of the restorative material, the teeth were randomly divided into two equally sized groups (n = 50): (polymer-infiltrated ceramic (Vita Enamic) and resin-based composites (Lava Ultimate)). The inlays were fabricated using CAD/CAM technology. In each group, the specimens were randomly assigned to five subgroups (n = 10) according to the surface treatment method: group 1 used was the control group (no surface treatment); group 2, was treated with air abrasion with 50 μm Al₂O₃ (A) and universal adhesive (UA); group 3, was treated with air abrasion with 50 μm Al₂O₃ (A) and silane coupling agent (S); group 4, was treated with hydrofluoric acid (HF) and universal adhesive (UA) and group 5, was treated with Hydrofluoric acid (HF) + silane coupling agent (S). The inlays were then cemented to their respective preparations using dual-cure self-adhesive resin cement (RelyX U200, 3 M ESPE) according to the manufacturer’s instructions. The µTBS test was conducted in all groups, and stereomicroscope and scanning electron microscope were used to inspect the failure mode. The data were statistically analyzed using a two-way analysis of variance (ANOVA) and Tukey’s post-hoc multiple comparison tests at a significance level of p < 0.05.

RESULTS: Surface treatments significantly increased the µTBS of the materials compared to the control group (p < 0.05). For CAD/CAM RBCs, the µTBS value highest in group 2 whereas, for PICN, the µTBS value was highest in group 3. Cohesive failure of CAD/CAM restorative material was the most predominant mode of failure in all treated groups, whereas adhesive failure at restoration-cement interface was the most predominant failure mode in the control group.

CONCLUSION: Surface treatments increase the µTBS of resin-matrix CAD/CAM ceramics to tooth structure. Air abrasion followed by universal adhesive and hydrofluoric acid followed by silane application appears to be the best strategies for optimizing the bond strength of CAD/CAM RBCs and PICN respectively.

PMID:36564766 | DOI:10.1186/s12903-022-02674-5

BMC Endocr Disord. 2022 Dec 23;22(1):330. doi: 10.1186/s12902-022-01205-1.

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) adversely affects reproduction. We aimed to study the effect of a high-fat diet (HFD), supplemented with apple vinegar, on folliculogenesis in a rat model of NAFLD.

METHODS: Female rats were randomly divided into four groups (N = 28): Standard diet (SD), SD + vinegar, HFD, and HFD + vinegar groups. At the end of the study, biochemical tests were assessed in serum. HOMA-IR (Homeostatic model assessment-Insulin resistance) was calculated. Sex hormones were determined using an ELISA kit; ovary follicle counts were studied using histological methods. The proliferation index of granulosa cells was determined using immunohistochemistry. Kisspeptin expression in the ovary was detected using RT-PCR.

RESULTS: The HFD induced steatohepatitis and NAFLD. The ovaries in the rat model of NAFLD were atrophied. The ovaries had less count of developing follicles and corpus luteum, and more degenerated and cystic follicles in comparison with the SD group. Vinegar + HFD consumption decreased ALT, compared to the HFD group (P = 0.004). Steatohepatitis was reduced in the Vinegar + HFD group (P = 0.001). Vinegar + HFD considerably reduced HOMA-IR (p = 0.01). The HFD + vinegar diet could increase estradiol (P = 0.001), without significantly affecting progesterone or testosterone. In addition, an increase of primordial follicles as an ovarian reserve and also primary follicles were determined in the HFD + vinegar group. There were no statistical differences in the granulosa cell proliferation index in various follicle types between groups. HFD + vinegar significantly enhanced ovarian kisspeptin expression (p = 0.04).

CONCLUSIONS: The vinegar diet in a rat model of NAFLD raises estradiol, primordial, and small primary follicles, and increases ovarian kisspeptin expression indirectly. Insulin resistance and obesity were improved by apple vinegar, and anti-glycemic and anti-lipidemic effects were also determined. The supplementation of apple vinegar in NAFLD might be useful for ovary. However, it requires further investigation.

PMID:36564752 | DOI:10.1186/s12902-022-01205-1

Drug Metab Pers Ther. 2022 Dec 26. doi: 10.1515/dmpt-2022-0112. Online ahead of print.

ABSTRACT

OBJECTIVES: Determine the frequency of actionable mutations in non-small cell lung cancer (NSCLC) and their correlation with overall survival (OS) and the site of metastases.

METHODS: We performed a descriptive cross-sectional study at the Hospital de Especialidades Eugenio Espejo, Ecuador, between 2017 and 2020. Demographic, pathological, and molecular alterations in epidermal growth factor (EGFR), Anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), Programmed death-ligand 1 (PD-L1) expression, and clinical data detailed in patients’ medical records with metastatic NSCLC were collected and analyzed. Seventy-nine stage IV patients had NSCLC; adenocarcinoma histology represents 56 (70.9%). The predominant mutation was in EGFR (22.8%); the most common variant was the deletion of exon 19 (72.2%). The most common metastatic site was in the contralateral lung (22.3%); however, this variable showed no significant correlation to the molecular markers (p=0.057). The overall survival (OS) and the status of molecular markers are not statistically significant (p=0.27). OS was better for non-mutated EGFR than for mutated EGFR (p=0.012). However, the frequency values are unrelated to contralateral lung metastasis or survival.

CONCLUSIONS: Our frequency mutations are concordant with those found in other studies in Latin America. EGFR was the most common biomarker mutation, and there was a better OS in EGFR non-mutated patient.

PMID:36563403 | DOI:10.1515/dmpt-2022-0112

J Am Acad Orthop Surg. 2022 Dec 22. doi: 10.5435/JAAOS-D-22-00261. Online ahead of print.

ABSTRACT

INTRODUCTION: High-energy periarticular tibia fractures are challenging injuries with a significant risk of complications. Postoperative infection rates, although improved, remain unacceptable. Intrawound topical antibiotic (TA) application has been popularized to reduce postoperative infections. Although TA may minimize infections, it remains unclear whether TAs have any impact on the development of nonunion. Recent investigations of TA use in fracture care have questioned its efficacy in vivo and suggested a potentially deleterious effect on fracture healing. This study investigates the impact of TA on nonunion rates in surgically treated high-energy periarticular tibia fractures.

METHODS: Retrospective analysis of surgically treated periarticular tibia fractures at a single Level 1 trauma center was conducted. Intervention in question was the clinical effect of intrawound TA powder application at definitive closure. A total of 222 high-energy periarticular tibia fractures were included, 114 with TA use and 108 without. The primary outcome was the occurrence of nonunion, with secondary outcomes being superficial and deep postoperative surgical site infections.

RESULTS: Twenty-seven patients (12.1%) were diagnosed with nonunions (14 pilons and 13 plateaus). There was no statistically significant difference in nonunion rates among patients who received topical antibiotics (15.8%) versus the group of patients who did not (8.3%) (P = 0.23). Odds of developing nonunion was significant for open injuries (odds ratio 6.16, P < 0.001) and patients with a provisional external fixator (odds ratio 8.72, P = 0.03) before definitive fixation. No notable difference in the number of superficial and deep infections was identified between groups.

CONCLUSION: The use of TA in high-energy periarticular tibia fractures showed no statistically significant increase in nonunion rates but did not conclusively rule out nonunion as a possible effect of intrawound TA. Additional large-scale multicenter prospective studies are needed to confirm these findings. The current body of literature regarding high-energy periarticular tibia fractures does suggest that TAs lower the risk of postoperative infections, but the nonunion risk remains unclear.

LEVEL OF EVIDENCE: Level III, Retrospective Cohort Study.

PMID:36563331 | DOI:10.5435/JAAOS-D-22-00261

Stat Med. 2022 Dec 23. doi: 10.1002/sim.9636. Online ahead of print.

ABSTRACT

In this paper we propose a new robust estimation of precision matrices for high-dimensional data when the number of variables is larger than the sample size. Different from the existing methods in literature, the proposed model combines the technique of modified Cholesky decomposition (MCD) with the robust generalized M-estimators. The MCD reparameterizes a precision matrix and transforms its estimation into solving a series of linear regressions, in which the commonly used robust techniques can be conveniently incorporated. Additionally, the proposed method adopts the model averaging idea to address the ordering issue in the MCD approach, resulting in an accurate estimation for precision matrices. Simulations and real data analysis are conducted to illustrate the merits of the proposed estimator.

PMID:36563324 | DOI:10.1002/sim.9636

Am J Gastroenterol. 2022 Dec 23. doi: 10.14309/ajg.0000000000002088. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence on the comparative diagnostic performance of endoscopic ultrasound (EUS)-based techniques for pancreatic cyst lesions (PCLs) is limited. This network meta-analysis comprehensively compared EUS-based techniques for PCLs diagnosis.

METHODS: A comprehensive literature search was performed for all comparative studies assessing the accuracy of 2 or more modalities for PCLs diagnosis. The primary outcome was the diagnostic efficacy for mucinous PCLs. Secondary outcomes were the diagnostic efficacy for malignant PCLs, diagnostic success rate, and adverse event rate. A network meta-analysis was conducted using the ANOVA model to assess the diagnostic accuracy of each index.

RESULTS: Forty studies comprising 3641 patients were identified. The network ranking of the superiority index for EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) and EUS-guided through-the-needle biopsy (EUS-TTNB) were significantly higher than other techniques for differentiating mucinous PCLs; besides, EUS-TTNB was also the optimal technique in identifying malignant PCLs. The evidence was inadequate for EUS-nCLE diagnosing malignant PCLs and CH-EUS for diagnosing both mucinous and malignant PCLs. Glucose showed a high sensitivity but low specificity, and molecular analysis (KRAS, GNAS and KRAS+GNAS mutations) showed a high specificity but low sensitivity for diagnosing mucinous PCLs. Satisfactory results were not obtained during the evaluation of the efficiency of pancreatic cyst fluid (PCF) biomarkers in detecting malignant PCLs.

CONCLUSIONS: For centers with relevant expertise and facilities, EUS-TTNB and EUS-nCLE were better choices for the diagnosis of PCLs. Further studies are urgently required for further improving PCF biomarkers and validating diagnostic performance of the index techniques.

PMID:36563321 | DOI:10.14309/ajg.0000000000002088

Am J Gastroenterol. 2022 Dec 23. doi: 10.14309/ajg.0000000000002118. Online ahead of print.

ABSTRACT

INTRODUCTION: Patency capsule (PC) is a recommended procedure to rule-out small-bowel stenosis before video capsule endoscopy (VCE). We examined future clinical outcomes among patients with failed-PC versus patients in whom PC had passed (passed-PC).

METHODS: A Post-hoc analysis of two prospective cohort studies of adult patients with quiescent small-bowel CD that underwent PC between 2013-2020. The primary composite-outcome was the need for intestinal-surgery or endoscopic-dilation during follow-up in patients with or without failed-PC.

RESULTS: A total of 190 patients were included (47-failed PC, 143-passed PC, median follow-up 34.12 months). Patients with a failed-PC had higher rates of the primary composite-outcome (21.3% vs. 1.4%, Hazard ratio [HR] 20.3, 95% confidence interval [CI] 4.4-93.7, p<0.001) and also secondary outcomes including intestinal-surgery (14.9% vs. 0.70%, p<0.001), endoscopic-dilation (14.9% vs. 0.70%, p<0.001), admissions (23.3% vs. 5.7%, p<0.001) and clinical-flares (43.9% vs. 27.7%, p=0.005) during follow-up compared with controls. Failed-PC was the only statistically significant factor for surgery and/or endoscopic-dilation, regardless of a B2/B3 phenotype at baseline. In sensitivity-analyses restricted only to patients with stricturing phenotype (n=73), failed-PC still predicted worse long-term composite-outcome (HR 8.68 95% CI 1.72-43.68, p=0.002). Of the 190 patients ingesting a PC, only one patient with a failed-PC had 48 hours of self-limiting mild symptoms.

DISCUSSION: Clinically-stable CD patients with failed-PC have worse long-term clinical outcomes than those without, independently of CD phenotype. Standalone PC may serve as a novel, safe and affordable prognostic examination, to identify patients with quiescent CD who have a higher risk for future worse clinical outcomes.

PMID:36563317 | DOI:10.14309/ajg.0000000000002118

Am J Gastroenterol. 2022 Dec 22. doi: 10.14309/ajg.0000000000002108. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Nocebo effects are thought to influence the rate of reported adverse events (AEs) and subject withdrawal in both the treatment and placebo groups of randomized clinical trials (RCTs). Neuromodulators are commonly prescribed to treat disorders of gut-brain interaction (DGBIs), but adherence to these medications is often limited by side effects such as headache, dry mouth, fatigue, and altered bowel habits. We performed a systematic review and meta-analysis to assess the proportion and risk difference of patients who experienced side effects leading to withdrawal in the placebo arm versus the treatment arm of RCTs of neuromodulators for DGBIs. We also sought to estimate the risk of developing any AE in the placebo arm of these studies as well as the rate of specific individual adverse events.

METHODS: We searched MEDLINE, Embase, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials Searches to identify RCTs that included terms for DGBIs and for commonly prescribed neuromodulators. We calculated pooled proportions of patients experiencing an AE leading to withdrawal in the active treatment group versus the placebo group with 95% confidence intervals (CI), the pooled proportions of patients experiencing any adverse event, the pooled proportions of patients experiencing specific adverse events such as dizziness and headache, the pooled proportions of patients experiencing severe adverse events and corresponding pooled risk differences with 95% CIs.

RESULTS: There were 30 RCTs included representing 2284 DGBI patients. 27 RCTs reported data on AEs leading to withdrawal. The pooled proportion of total patients with AEs leading to withdrawal in the placebo group was 4% (95% CI 0.02 – 0.04). The pooled proportion of patients with AEs leading to withdrawal who received neuromodulators was 9% (95% CI 0.06-0.13). In the 12 studies reporting data on patients experiencing at least one AE, the pooled proportion of patients experiencing any adverse event in the placebo group was 18% (95% CI 0.08 – 0.30), compared to 43% (95% CI 0.24 – 0.63) in the neuromodulator group. Thus, approximately 44% of the rate of withdrawal (0.04/0.09) and 42% of the rate reporting any side effects (0.18/0.43) in the neuromodulator group may be attributed to nocebo effects in the right context. Subgroup analysis by sex, medication class, risk of bias, and specific DGBIs revealed differing withdrawal rates. There was no statistically significant difference in patients experiencing individual AEs of dizziness, headache or diarrhea. Rates of dry mouth, fatigue and constipation were higher in treatment groups compared to placebo groups.

CONCLUSION: Patients with DGBIs in RCTs randomized to placebo groups frequently experience AEs and AEs that lead to withdrawal consistent with a strong nocebo effect. Non-specific AEs such as dizziness, headaches and diarrhea occurred similarly in patients receiving placebo compared to those receiving neuromodulators.

PMID:36563308 | DOI:10.14309/ajg.0000000000002108