Categories
Nevin Manimala Statistics

Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein

Sci Signal. 2023 Jun 13;16(789):eadd3184. doi: 10.1126/scisignal.add3184. Epub 2023 Jun 13.

ABSTRACT

The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which contains a docking site for substrates called the PIF pocket. Here, we used a chemical biology approach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities. The inositol polyphosphate derivative HYG8 bound to the PH domain and disrupted PDK1 dimerization by stabilizing a monomeric conformation in which the PH domain associated with the catalytic domain and the PIF pocket was accessible. In the absence of lipids, HYG8 potently inhibited the phosphorylation of Akt (also termed PKB) but did not affect the intrinsic activity of PDK1 or the phosphorylation of SGK, which requires docking to the PIF pocket. In contrast, the small-molecule valsartan bound to the PIF pocket and stabilized a second distinct monomeric conformation. Our study reveals dynamic conformations of full-length PDK1 in which the location of the linker and the PH domain relative to the catalytic domain determines the selective phosphorylation of PDK1 substrates. The study further suggests new approaches for the design of drugs to selectively modulate signaling downstream of PDK1.

PMID:37311034 | DOI:10.1126/scisignal.add3184

Categories
Nevin Manimala Statistics

Effects of Different Levels of Surgical Separation on Neck Bulge and Swallowing Disorders during Endoscopic Thyroidectomy

Surg Laparosc Endosc Percutan Tech. 2023 May 23. doi: 10.1097/SLE.0000000000001183. Online ahead of print.

ABSTRACT

OBJECTIVE: Our study aims to compare the effects of different levels of access on postoperative neck bulge and swallowing disorder and provide a better level for endoscopic thyroidectomy.

MATERIALS AND METHODS: The patients were selected retrospectively between March 2021 to September 2021 by the Department of Thyroid Surgery, Third Affiliated Hospital of Zunyi Medical University. They were divided into two groups according to the level of the free flap during surgery: group A (the superficial cervical fascial level) and group B (the superficial deep cervical fascial level). Age, sex, body mass index, diameter of the primary lesion, postoperative neck bulge, and swallowing disorders and other complications were compared between the two groups.

RESULTS: A total of 40 patients who underwent endoscopic unilateral lobectomy plus central region lymph node dissection were enrolled in our study. Twenty in group A and 20 in group B. The age, gender, body mass index, diameter, and the proportion of benign and malignant primary lesions were not significantly different between the two groups (P>0.05), and there was also no difference in thyroid function between the two groups (P>0.05). No significant differences were observed in terms of bleeding and operation time during the operation (P>0.05). There were also no statistical differences in terms of recurrent laryngeal nerve injury or hypoparathyroidism (P>0.05). However, patients in group B were superior to those in group A in the occurrence of neck bulge and swallowing disorders (P<0.05). These symptoms were most evident one month after surgery. Six months after the operation, only 4 patients in group B still complained of neck “swelling” and uncomfortable straining which did not resolve until 1 year after the operation. No statistical significance between long-term results and complication rates could be observed in either group.

CONCLUSION: In endoscopic thyroidectomy, the superficial cervical fascial level may be a better option for reducing postoperative neck bulge and swallowing disorders, which needs further validation by conducting a large sample study.

PMID:37311030 | DOI:10.1097/SLE.0000000000001183

Categories
Nevin Manimala Statistics

Laparoscopic Surgery for Acute Right-colon Diverticulitis: Video Vignette and Systematic Review With Meta-analysis of Current Evidence of Minimally Invasive Versus Conventional Surgery

Surg Laparosc Endosc Percutan Tech. 2023 May 30. doi: 10.1097/SLE.0000000000001186. Online ahead of print.

ABSTRACT

BACKGROUND: Over the last decade, there has been growing diffusion of minimally invasive surgery in the setting of abdominal emergencies. However, right-colon diverticulitis is still mainly approached by conventional celiotomy.

MATERIALS AND METHODS: A video vignette is presented showing the details of an emergent laparoscopic right colectomy as performed to treat a 59-year-old woman who presented with clinical signs of peritonitis, and radiologic findings suggestive of acute right-colon diverticulitis complicated by perforation of the hepatic flexure and periduodenal abscess. We also aimed to evaluate the relative outcomes of laparoscopic versus conventional surgery by meta-analyzing the currently available comparative evidence on the argument.

RESULTS: A total of 2848 patients were included in the analysis, of which 979 patients received minimally invasive surgery and 1869 had conventional surgery. Laparoscopic surgery had a longer operating time and resulted in an abbreviated hospital stay. Overall, patients receiving laparoscopy had significantly lower morbidity than those whose surgery was undertaken by laparotomy, while there was no statistically significant difference in terms of postoperative mortality.

CONCLUSIONS: According to the existing literature, minimally invasive surgery improves the postoperative outcomes of patients receiving surgery for right-sided colonic diverticulitis.

PMID:37311024 | DOI:10.1097/SLE.0000000000001186

Categories
Nevin Manimala Statistics

Optic Nerve Head Changes After Intraocular Pressure-Lowering Glaucoma Surgeries Using Optical Coherence Tomography

J Glaucoma. 2023 May 25. doi: 10.1097/IJG.0000000000002242. Online ahead of print.

ABSTRACT

PRCIS: Optic nerve head changes were detected with swept-source optical coherence tomography after intraocular pressure-lowering glaucoma surgeries.

PURPOSE: The aim of this study was to detect changes in the optic nerve head with swept-source optical coherence tomography (SS-OCT) after intraocular pressure-lowering procedures.

METHODS: Patients with progressing glaucoma who were referred for intraocular pressure-lowering procedures were included. The participants underwent a 24-2 visual field test and SS-OCT (DRI OCT Triton Plus; Topcon, Tokyo, Japan). Intraocular pressure and SS-OCT scans were obtained during the preoperative period and up to 7 days and 30-90 days postoperatively. Optic nerve head parameters were measured with a B-scan at the center of the optic disc and an average of 5 central B-scans. The hypotenuse of the optic nerve head cup was calculated using the Pythagorean theorem: hypotenuse2 = leg12 + leg22, considering the length and depth of the cup as the legs of a right triangle. We also evaluated changes in Bruch’s membrane opening-to-Bruch’s membrane opening diameter. Statistical analysis was performed using generalized estimating equations.

RESULTS: A total of 15 eyes were included. The mean patient age was 70 (SD, 11.04) years. The mean circumpapillary retinal nerve fiber layer was 60.13 (SD, 23.21) µm and the visual field mean deviation was -13.29 (SD, 8.5) dB. The mean intraocular pressure at each visit was: 20.5 (SD, 4.99); 11 (SD, 4.95) and 15.7 (SD, 5.04), respectively. The mean hypotenuse of the optic nerve head cup, the mean depth and length of the optic nerve head cup, and the Bruch’s membrane opening-to-Bruch’s membrane opening diameter decreased significantly after the intraocular pressure-lowering procedures.

CONCLUSIONS: The hypotenuse of the optic nerve head cup evaluated with SS-OCT significantly decreased after intraocular pressure-lowering surgeries. This parameter was useful for evaluating short-term changes in the optic nerve head.

PMID:37311019 | DOI:10.1097/IJG.0000000000002242

Categories
Nevin Manimala Statistics

Widespread partisan gerrymandering mostly cancels nationally, but reduces electoral competition

Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2217322120. doi: 10.1073/pnas.2217322120. Epub 2023 Jun 13.

ABSTRACT

Congressional district lines in many US states are drawn by partisan actors, raising concerns about gerrymandering. To separate the partisan effects of redistricting from the effects of other factors including geography and redistricting rules, we compare possible party compositions of the US House under the enacted plan to those under a set of alternative simulated plans that serve as a nonpartisan baseline. We find that partisan gerrymandering is widespread in the 2020 redistricting cycle, but most of the electoral bias it creates cancels at the national level, giving Republicans two additional seats on average. Geography and redistricting rules separately contribute a moderate pro-Republican bias. Finally, we find that partisan gerrymandering reduces electoral competition and makes the partisan composition of the US House less responsive to shifts in the national vote.

PMID:37310996 | DOI:10.1073/pnas.2217322120

Categories
Nevin Manimala Statistics

Coach-Supported Versus Self-guided Digital Training Course for a Problem-solving Psychological Intervention for Nonspecialists: Protocol for a Pre-Post Nested Randomized Controlled Trial

JMIR Res Protoc. 2023 Jun 13;12:e41981. doi: 10.2196/41981.

ABSTRACT

BACKGROUND: Psychosocial interventions delivered by nonspecialists can be effective at reducing common adolescent mental health problems in low-resource settings. However, there is a lack of evidence on resource-efficient methods for building capacity to deliver these interventions.

OBJECTIVE: The objective of this study is to evaluate the effects of a digital training (DT) course, delivered in a self-guided format or with coaching, on nonspecialists’ competency to deliver a problem-solving intervention intended for adolescents with common mental health problems in India.

METHODS: We will conduct a pre-post study with a nested parallel, 2-arm, individually randomized controlled trial. The study aims to recruit 262 participants, randomized 1:1 to receive either a self-guided DT course or a DT course with weekly individualized coaching provided remotely by telephone. In both arms, the DT will be accessed over 4 to 6 weeks. Participants will be nonspecialists (ie, without prior practice-based training in psychological therapies) recruited from among university students and affiliates of nongovernmental organizations in Delhi and Mumbai, India.

RESULTS: Outcomes will be assessed at baseline and 6 weeks post randomization using a knowledge-based competency measure that incorporates a multiple-choice quiz format. The primary hypothesis is that self-guided DT will lead to increased competency scores among novices with no prior experience of delivering psychotherapies. The secondary hypothesis is that digital training with coaching will have an incremental effect on competency scores compared with DT alone. The first participant was enrolled on April 4, 2022.

CONCLUSIONS: The study will address an evidence gap on the effectiveness of training methods for nonspecialist providers of adolescent mental health interventions in low-resource settings. The findings from this study will be used to support wider efforts to scale up evidence-based mental health interventions for young people.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05290142; https://clinicaltrials.gov/ct2/show/NCT05290142.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41981.

PMID:37310781 | DOI:10.2196/41981

Categories
Nevin Manimala Statistics

Reliability and agreement in intrapartum fetal heart rate monitoring interpretation: A systematic review

Acta Obstet Gynecol Scand. 2023 Jun 13. doi: 10.1111/aogs.14591. Online ahead of print.

ABSTRACT

INTRODUCTION: Fetal heart rate (FHR) monitoring is routine in intrapartum care worldwide and one of the most common obstetrical procedures. Intrapartum FHR monitoring helps assess fetal wellbeing and interpretation of the FHR help form decisions for clinical management and intervention. It relies on the observers’ subjective assessments, with variation in interpretations leading to variations in intrapartum care. The purpose of this systematic review was to summarize and evaluate extant inter- and intrarater reliability research on the human interpretation of intrapartum FHR monitoring.

MATERIAL AND METHODS: We searched for the terms “fetal heart rate monitoring,” “interpretation agreement” and related concepts on Embase, Medline, Maternity and Infant Care Database and CINAHL. The last search was made on January 31, 2022. The protocol for the study was prospectively registered in PROSPERO (CRD42021260937). Studies that assess inter- and intrarater reliability and agreement of health professionals’ intrapartum FHR monitoring were included and studies including other assessment of fetal wellbeing excluded. We extracted data in reviewer pairs using quality appraisal tool for studies of diagnostic reliability (QAREL) forms. The data retrieved from the studies are presented as narrative synthesis and in additional tables.

RESULTS: Forty-nine articles concerning continuous FHR monitoring were included in the study. For interrater reliability and agreement, in total 577 raters assessed 6315 CTG tracings. There was considerable heterogeneity in quality and measures across the included articles. We found higher reliability and agreement for the basic FHR features than for overall classification and higher agreement for intrarater reliability and agreement than for their interrater counterparts.

CONCLUSIONS: There is great variation in reliability and agreement measures for continuous intrapartum FHR monitoring, implying that intrapartum CTG should be used with caution for clinical decision making given its questionable reliability. We found few high-quality studies and noted methodological concerns in the studies. We recommend a more standardized approach to future reliability studies on FHR monitoring.

PMID:37310765 | DOI:10.1111/aogs.14591

Categories
Nevin Manimala Statistics

Gender and Research Productivity of Vitreoretinal Surgery Fellowship Program Directors

Ophthalmic Surg Lasers Imaging Retina. 2023 Jun 1:1-3. doi: 10.3928/23258160-20230522-01. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Characteristics of vitreoretinal surgery fellowship program directors (PDs) in North America are not well described. This study reports on the gender and research productivity of vitreoretinal surgery PDs in the United States and Canada.

MATERIALS AND METHODS: We reviewed demographics, total number of Scopus-indexed publications, h-index, and m-quotient for vitreoretinal surgery fellowship PDs in 2022. Descriptive statistics, student t-tests, χ2 tests, and logistic regression analyses were performed.

RESULTS: Information was obtained on 83/89 (93%) PDs; 86% were male, and 84% did not have an additional graduate degree. The mean publication count was 81.54 (SD: 90.33) and mean h-index was 20.61 (SD: 16.49). There were no significant differences between female and male fellowship PDs with respect to number of publications, h-indices, and m-quotients.

CONCLUSION: Women were underrepresented among vitreoretinal fellowship PDs although they had similar research productivity as their male colleagues. [Ophthalmic Surg Lasers Imaging Retina 2023;54:xx-xx.].

PMID:37310752 | DOI:10.3928/23258160-20230522-01

Categories
Nevin Manimala Statistics

The Global Status of Occupational Therapy Workforce Research Worldwide: A Scoping Review

Am J Occup Ther. 2023 May 1;77(3):7703205080. doi: 10.5014/ajot.2023.050089.

ABSTRACT

IMPORTANCE: To fulfill their societal role, occupational therapists need to exist in sufficient supply, be equitably distributed, and meet competency standards. Occupational therapy workforce research is instrumental in reaching these aims, but its global status is unknown.

OBJECTIVE: To map the volume and nature (topics, methods, geography, funding) of occupational therapy workforce research worldwide.

DATA SOURCES: Six scientific databases (MEDLINE/PubMed, Scopus, CINAHL, Web of Science Core Collection, PDQ-Evidence for Informed Health Policymaking, OTseeker), institutional websites, snowballing, and key informants.

STUDY SELECTION AND DATA COLLECTION: Research articles of any kind were included if they involved data regarding occupational therapists and addressed 1 of 10 predefined workforce research categories. Two reviewers were used throughout study selection. No language or time restrictions applied, but the synthesis excluded publications before 1996. A linear regression examined the publications’ yearly growth.

FINDINGS: Seventy-eight studies met the inclusion criteria, 57 of which had been published since 1996. Although significant (p < .01), annual publication growth was weak (0.07 publications/yr). “Attractiveness and retention” was a common topic (27%), and cross-sectional surveys were frequent study designs (53%). Few studies used inferential statistics (39%), focused on resource-poor countries (11%), used standardized instruments (10%), or tested a hypothesis (2%). Only 30% reported funding; these studies had stronger methodology: 65% used inferential statistics, and just 6% used exploratory cross-sectional surveys.

CONCLUSIONS AND RELEVANCE: Worldwide occupational therapy workforce research is scant and inequitably distributed, uses suboptimal methods, and is underfunded. Funded studies used stronger methods. Concerted efforts are needed to strengthen occupational therapy workforce research. What This Article Adds: This review highlights the opportunity to develop a stronger, evidence-based strategy for workforce development and professional advocacy.

PMID:37310749 | DOI:10.5014/ajot.2023.050089

Categories
Nevin Manimala Statistics

Effect of Occupational Therapy in Promoting Medication Adherence in Primary Care: A Randomized Controlled Trial

Am J Occup Ther. 2023 May 1;77(3):7703205040. doi: 10.5014/ajot.2023.050109.

ABSTRACT

IMPORTANCE: The Integrative Medication Self-Management Intervention (IMedS) is a manualized occupational therapy intervention designed to improve adherence to medications. The intervention influences medication adherence and facilitates new medication habits and routines; however, it has not been tested in a community clinical setting.

OBJECTIVE: To test the efficacy of the IMedS to address medication adherence rates among community-dwelling adults with hypertension (HTN), Type 2 diabetes mellitus (T2DM), or both.

DESIGN: Randomized controlled trial using a pretest-posttest control group design.

SETTING: Primary care clinic in a large federally qualified health center.

PARTICIPANTS: Adults with uncontrolled HTN, T2DM, or both.

INTERVENTION: Participants were divided into two groups: The control group received treatment as usual (TAU) per the primary care protocol, and the intervention IMedS group received TAU and the IMedS intervention.

OUTCOMES AND MEASURES: Primary outcome: seven-item version of the Adherence to Refills and Medication Scale (ARMS-7), pill count, blood pressure, hemoglobin A1c, or all of these.

RESULTS: The proportion of adherent participants increased in both groups, but between groups, changes were not statistically significant. Post hoc comparisons of the results of a mixed analysis of variance for ARMS-7 measurements indicated that the occupational therapy intervention had a unique effect, compared with that for the TAU control group (dc = 0.65). Effect scores for pill count (d = 0.55) also suggested that the occupational therapy intervention positively affected adherence.

CONCLUSIONS AND RELEVANCE: Occupational therapists can provide assessment and intervention to positively influence medication adherence in a primary care setting. What This Article Adds: This article provides a better understanding of the occupational therapist’s role in addressing medication management and adherence on the interdisciplinary primary care medical team.

PMID:37310747 | DOI:10.5014/ajot.2023.050109