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Indian Journal of Public Health Apr 2024There are several leadership training programs for health researchers in India. However, there is a need to develop context-tailored leadership and mentoring approaches.
BACKGROUND
There are several leadership training programs for health researchers in India. However, there is a need to develop context-tailored leadership and mentoring approaches.
OBJECTIVE
The objective of the study is to critically analyze the available leadership training programs in India for health researchers and service providers, for the leadership domains incorporated and overall training approaches.
MATERIALS AND METHODS
We used an exploratory-descriptive design to identify and review leadership training programs for health researchers and service providers/managers that had been offered by Indian institutions between 2013 and 2018. Our analytic approach was based on "transformational leadership" and "leader-member exchange" theories of leadership, curricula of popular leadership training programs worldwide, and the International Clinical Epidemiology Network model for leadership in health research in India based on a nationwide primary study.
RESULTS
We identified and reviewed 20 leadership training programs. These were heterogeneous in aim, scope (broad-based/thematic), course content, design, target participants and class profile, mode of delivery and training method, duration, frequency, and fund arrangements. The programs infrequently included topics on soft skills, mentoring, risk mitigation, collaboration for research, funding dynamics, institutional transformation, self-view and peer perception, and personal well-being. The programs insufficiently addressed contextual challenges of career exploration and risk mitigation, project management, strategic planning, and decision-making, ethics and integrity, negotiations, networking and collaboration, understanding funding dynamics, and mentoring. Only three programs linked to the training to the participants' ecosystem.
CONCLUSIONS
There is a need to develop customized course contents and training strategies that address the requirements of the local context vis-à-vis globally connected research ecosystems.
Topics: Leadership; India; Humans; Curriculum; Research Personnel; Health Services Research; Mentoring
PubMed: 38953813
DOI: 10.4103/ijph.ijph_762_23 -
Expert Opinion on Pharmacotherapy Jul 2024During menopause the majority of women experience vasomotor symptoms which may lead to several untoward effects and negatively impact quality of life. Fezolinetant, a,... (Review)
Review
INTRODUCTION
During menopause the majority of women experience vasomotor symptoms which may lead to several untoward effects and negatively impact quality of life. Fezolinetant, a, novel agent directly targeting the underlying pathophysiology of menopause-associated vasomotor symptoms offers an alternative to hormonal therapies for which many patients have a contraindication or unwillingness to take due to safety concerns.
AREAS COVERED
This review summarizes key pharmacologic, pharmacokinetic, and pharmacodynamic parameters of fezolinetant along with efficacy and safety data derived from clinical trials. A literature search of peer-reviewed publications evaluating the efficacy and safety of fezolinetant was conducted using PubMed and EMBASE databases. A review of registered trials in clinicaltrials.gov was evaluated to identify ongoing studies.
EXPERT OPINION
Placebo-controlled studies demonstrated that fezolinetant led to a statistically significant reduction in vasomotor symptom frequency and severity among patients with moderate to severe vasomotor symptoms. The most common adverse event is headache (5-10%) and no serious safety signals have been noted. Direct head-to-head comparison with hormonal therapies and nonhormonal therapies for VMS, assessment of sleep outcomes, and evaluation of efficacy and safety beyond one year are key areas where additional data is still needed.
PubMed: 38953697
DOI: 10.1080/14656566.2024.2375039 -
American Journal of Health-system... Jul 2024In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been...
Optimizing discharge antimicrobial therapy: Evaluation of a transitions of care process and electronic scoring system for patients with community-acquired pneumonia or chronic obstructive pulmonary disease.
DISCLAIMER
In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
PURPOSE
Prescribing excess antibiotic duration at hospital discharge is common. A pharmacist-led Antimicrobial Stewardship Program Transition of Care (ASP TOC) intervention was associated with improved discharge prescribing. To improve the sustainability of this service, an electronic scoring system (ESS), which included the ASP TOC electronic variable, was implemented in the electronic medical record to prioritize pharmacist workload. The purpose of this study was to evaluate the implementation of the ASP TOC variable in the ESS in patients with community-acquired pneumonia (CAP) or chronic obstructive pulmonary disease (COPD).
METHODS
This institutional review board-approved, retrospective quasi-experiment included patients discharged on oral antibiotics for CAP or COPD exacerbation (lower respiratory tract infection) from November 1, 2021, to March 1, 2022 (the preintervention period) and November 1, 2022, to March 1, 2023 (the postintervention period). The primary endpoint was optimized discharge antimicrobial regimen. A sample of at least 194 patients was required to achieve 80% power to detect a 20% difference in the frequency of optimized therapy. Multivariable logistic regression was used to identify factors associated with optimized regimens.
RESULTS
Similar baseline characteristics were observed in both study groups (n = 100 for both groups). The frequency of optimized discharge regimens improved from 69% to 82% (P = 0.033). The percentage of ASP TOC interventions documented as completed by a pharmacist increased from 4% to 25% (P < 0.001). ASP TOC intervention, female gender, and COPD were independently associated with an optimized discharge regimen (adjusted odds ratios, 6.57, 1.61, and 3.89, respectively; 95% CI, 1.51-28.63, 0.81-3.17, and 1.85-8.20, respectively).
CONCLUSION
After the launch of the ASP TOC variable, there was an increase in optimized discharge regimens and ASP TOC interventions completed. Pharmacists' use of the ASP TOC variable through an ESS can aid in improving discharge prescribing.
PubMed: 38953520
DOI: 10.1093/ajhp/zxae174 -
Frontiers in Pharmacology 2024Diabetic retinopathy is a secondary microvascular complication of diabetes mellitus. This disease progresses from two stages, non-proliferative and proliferative...
Diabetic retinopathy is a secondary microvascular complication of diabetes mellitus. This disease progresses from two stages, non-proliferative and proliferative diabetic retinopathy, the latter characterized by retinal abnormal angiogenesis. Pharmacological management of retinal angiogenesis employs expensive and invasive intravitreal injections of biologic drugs (anti-vascular endothelial growth factor agents). To search small molecules able to act as anti-angiogenic agents, we focused our study on axitinib, which is a tyrosine kinase inhibitor and represents the second line treatment for renal cell carcinoma. Axitinib is an inhibitor of vascular endothelial growth factor receptors, and among the others tyrosine kinase inhibitors (sunitinib and sorafenib) is the most selective towards vascular endothelial growth factor receptors 1 and 2. Besides the well-known anti-angiogenic and immune-modulatory functions, we hereby explored the polypharmacological profile of axitinib, through a bioinformatic/molecular modeling approach and models of diabetic retinopathy. We showed the anti-angiogenic activity of axitinib in two different models of diabetic retinopathy, by challenging retinal endothelial cells with high glucose concentration (fluctuating and non-fluctuating). We found that axitinib, along with inhibition of vascular endothelial growth factor receptors 1 (1.82 ± 0.10; 0.54 ± 0.13, phosphorylated protein levels in fluctuating high glucose axitinib 1 µM, respectively) and vascular endothelial growth factor receptors 2 (2.38 ± 0.21; 0.98 ± 0.20, phosphorylated protein levels in fluctuating high glucose axitinib 1 µM, respectively), was able to significantly reduce ( < 0.05) the expression of Nrf2 (1.43 ± 0.04; 0.85 ± 0.01, protein levels in fluctuating high glucose axitinib 1 µM, respectively) in retinal endothelial cells exposed to high glucose, through predicted Keap1 interaction and activation of melanocortin receptor 1. Furthermore, axitinib treatment significantly ( < 0.05) decreased reactive oxygen species production (0.90 ± 0.10; 0.44 ± 0.06, fluorescence units in high glucose axitinib 1 µM, respectively) and inhibited ERK pathway (1.64 ± 0.09; 0.73 ± 0.06, phosphorylated protein levels in fluctuating high glucose axitinib 1 µM, respectively) in HRECs exposed to high glucose. The obtained results about the emerging polypharmacological profile support the hypothesis that axitinib could be a valid candidate to handle diabetic retinopathy, with ancillary mechanisms of action.
PubMed: 38953109
DOI: 10.3389/fphar.2024.1415846 -
Frontiers in Immunology 2024Mast cell (MC) degranulation is a key process in allergic reactions and inflammatory responses. Aspartate aminotransferase 1 (AAT1)-derived endogenous sulfur dioxide...
OBJECTIVES
Mast cell (MC) degranulation is a key process in allergic reactions and inflammatory responses. Aspartate aminotransferase 1 (AAT1)-derived endogenous sulfur dioxide (SO) is an important regulator of MC function. However, the mechanism underlying its role in MC degranulation remains unclear. This study aimed to investigate the mechanism by which endogenous SO controlled MC degranulation.
METHODS
HMC-1 and Rat basophilic leukemia cell MC line (RBL-2H3) were used in the cell experiments. SO content was detected by fluorescent probe. MC degranulation represented by the release rate of MC β-hexosaminidase was determined using a colorimetric assay. Sulfenylation of galectin-9 (Gal-9) in MCs and purified protein was detected using a biotin switch assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the exact sulfenylation sites of Gal-9 by SO. Animal models of passive cutaneous anaphylaxis (PCA) and hypoxia-driven pulmonary vascular remodeling were used to investigate the effect of SO on mast cell activation . Site-directed mutation of Gal-9 was conducted to confirm the exact site of SO and support the significance of SO/Gal-9 signal axis in the regulation of MC degranulation.
RESULTS
Degranulation was increased in AAT1-knockdowned MCs, and SO supplementation reversed the increase in MC degranulation. Furthermore, deficiency of endogenous SO contributed to IgE-mediated degranulation Besides, SO inhibited IgE-mediated and hypoxia-driven MC degranulation . Mechanistically, LC-MS/MS analysis and site-directed mutation results showed that SO sulfenylated Gal-9 at cysteine 74. Sulfenylation of the 74 cysteine of Gal-9 protein was required in the SO-inhibited MC degranulation under both physiological and pathophysiological conditions.
CONCLUSION
These findings elucidated that SO inhibited MC degranulation via sulfenylating Gal-9 under both physiological and pathophysiological conditions, which might provide a novel treatment approach for MC activation-related diseases.
Topics: Animals; Cell Degranulation; Mast Cells; Cysteine; Rats; Sulfur Dioxide; Humans; Galectins; Mice; Male; Passive Cutaneous Anaphylaxis; Cell Line
PubMed: 38953022
DOI: 10.3389/fimmu.2024.1369326 -
Frontiers in Immunology 2024P2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and...
INTRODUCTION
P2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell functions. While formation of P2X2/P2X3 heterotrimers produces a distinct pharmacological phenotype and has been well established, functional identification of a P2X4/P2X7 heteromer has been difficult and evidence for and against a physical association has been found. Most of this evidence stems, however, from model systems.
METHODS
Here, we used a P2X7-EGFP BAC transgenic mouse model as well as P2X4 and P2X7 knock-out mice to re-investigate a P2X4-P2X7 interaction in mouse lung by biochemical and immunohistochemical experiments as well as quantitative expression analysis.
RESULTS
No detectable amounts of P2X4 could be co-purified from mouse lung via P2X7-EGFP. In agreement with these findings, immuno-histochemical analysis using a P2X7-specific nanobody revealed only limited overlap in the cellular and subcellular localizations of P2X4 and P2X7 in both the native lung tissue and primary cells. Comparison of P2X4 and P2X7 transcript and protein levels in the respective gene-deficient and wild type mice showed no mutual interrelation between their expression levels in whole lungs. However, a significantly reduced expression was found in alveolar macrophages of mice.
DISCUSSION
In summary, our detailed analysis of the cellular and subcellular P2X4 and P2X7 localization and expression does not support a physiologically relevant direct association of P2X4 and P2X7 subunits or receptors .
Topics: Animals; Receptors, Purinergic P2X4; Receptors, Purinergic P2X7; Mice; Lung; Mice, Knockout; Mice, Transgenic; Mice, Inbred C57BL; Protein Binding
PubMed: 38953020
DOI: 10.3389/fimmu.2024.1425938 -
Frontiers in Big Data 2024Persuasive technologies, in connection with human factor engineering requirements for healthy workplaces, have played a significant role in ensuring a change in human...
Persuasive technologies, in connection with human factor engineering requirements for healthy workplaces, have played a significant role in ensuring a change in human behavior. Healthy workplaces suggest different best practices applicable to body posture, proximity to the computer system, movement, lighting conditions, computer system layout, and other significant psychological and cognitive aspects. Most importantly, body posture suggests how users should sit or stand in workplaces in line with best and healthy practices. In this study, we developed two study phases (pilot and main) using two deep learning models: convolutional neural networks (CNN) and Yolo-V3. To train the two models, we collected posture datasets from creative common license YouTube videos and Kaggle. We classified the dataset into comfortable and uncomfortable postures. Results show that our YOLO-V3 model outperformed CNN model with a mean average precision of 92%. Based on this finding, we recommend that YOLO-V3 model be integrated in the design of persuasive technologies for a healthy workplace. Additionally, we provide future implications for integrating proximity detection taking into consideration the ideal number of centimeters users should maintain in a healthy workplace.
PubMed: 38953011
DOI: 10.3389/fdata.2024.1359906 -
Frontiers in Cellular and Infection... 2024
Topics: Humans; Anti-Bacterial Agents; Bacteriophages; Drug Resistance, Multiple, Bacterial; Endopeptidases; Methicillin-Resistant Staphylococcus aureus; Phage Therapy; Staphylococcal Infections; Staphylococcus aureus
PubMed: 38953006
DOI: 10.3389/fcimb.2024.1397935 -
Frontiers in Physiology 2024Several fluorescent proteins (FPs) and chromoproteins (CPs) are present in anthozoans and play possible roles in photoprotection. Coral tissues in massive corals often...
INTRODUCTION
Several fluorescent proteins (FPs) and chromoproteins (CPs) are present in anthozoans and play possible roles in photoprotection. Coral tissues in massive corals often display discoloration accompanied by inflammation. Incidences of the pink pigmentation response (PPR) in massive , described as inflammatory pink lesions of different shapes and sizes, has recently increased worldwide. FPs are reported to be present in PPR lesions, wherein a red fluorescent protein (RFP) appears to play a role in reducing reactive oxygen species. However, to date, the biochemical characterization and possible roles of the pigments involved are poorly understood. The present study aimed to identify and characterize the proteins responsible for pink discoloration in massive colonies displaying PPRs, as well as to assess the differential distribution of pigments and the antioxidant properties of pigmented areas.
METHOD
CPs were extracted from PPR lesions using gel-filtration chromatography and identified via genetic analysis using liquid chromatography-tandem mass spectrometry. The coexistence of CPs and RFP in coral tissues was assessed using microscopic observation. Photosynthetic antivity and hydrogen peroxide-scavenging activitiy were measured to assess coral stress conditions.
RESULTS
The present study revealed that the same CP (plut2.m8.16902.m1) isolated from massive was present in both the pink spot and patch morphologies of the PPR. CPs were also found to coexist with RFP in coral tissues that manifested a PPR, with a differential distribution (coenosarc or tip of polyps' tentacles). High hydrogen peroxide-scavenging rates were found in tissues affected by PPR.
DISCUSSION AND CONCLUSION
The coexistence of CPs and RFP suggests their possible differential role in coral immunity. CPs, which are specifically expressed in PPR lesions, may serve as an antioxidant in the affected coral tissue. Overall, this study provides new knowledge to our understanding of the role of CPs in coral immunity.
PubMed: 38952870
DOI: 10.3389/fphys.2024.1339907 -
Frontiers in Psychology 2024Narrative identity allows individuals to integrate their personal experiences into a coherent and meaningful life story. Addictive disorders appear to be associated with... (Review)
Review
Narrative identity allows individuals to integrate their personal experiences into a coherent and meaningful life story. Addictive disorders appear to be associated with a disturbed sense of self, reflected in problematic and disorganized self-narratives. In recent literature, a growing body of research has highlighted how narrative approaches can make a dual contribution to the understanding of addiction: on the one hand, by revealing crucial aspects of self structure, and, on the other, by supporting the idea that addiction is a disorder related to unintegrated self-states in which dissociative phenomena and the resulting sense of 'loss of self' are maladaptive strategies for coping with distress. This conceptual review identified the main measures of narrative identity, i.e., narrative coherence and complexity, agency, and emotions, and critically examines 9 quantitative and qualitative studies (out of 18 identified in literature), that have investigated the narrative dimension in people with an addictive disorder in order to provide a synthesis of the relationship between self, narrative and addiction. These studies revealed a difficulty in the organization of narrative identity of people with an addictive disorder, which is reflected in less coherent and less complex autobiographical narratives, in a prevalence of passivity and negative emotions, and in a widespread presence of themes related to a lack of self-efficacy. This review points out important conceptual, methodological and clinical implications encouraging further investigation of narrative dimension in addiction.
PubMed: 38952822
DOI: 10.3389/fpsyg.2024.1409217