Culture change and lessons learned from ten years in the VA centers of excellence in primary care education.

BACKGROUND: Team-based care is critical to achieving health care value while maximizing patient outcomes. Few descriptions exist of graduate-level team training interventions and practice models. Experience from the multisite, decade-long Veterans Affairs (VA) Centers of Excellence in Primary Care Education provides lessons for developing internal medicine training experiences in interprofessional clinical learning environments. METHODS: A review of multisite demonstration project transforming traditional silo-model training to interprofessional team-based primary care. Using iterative quality improvement approaches, sites evaluated curricula with learner, faculty and staff feedback. Learner- and patient-level outcomes and organizational culture change were examined using mixed methods, within and across sites. Participants included more than 1600 internal medicine, nurse practitioner, nursing, pharmacy, psychology, social work and physical therapy trainees. This took place in seven academic university-affiliated VA primary care clinics with patient centered medical home design RESULTS: Each site developed innovative design and curricula using common competencies of shared decision making, sustained relationships, performance improvement and interprofessional collaboration. Educational strategies included integrated didactics, workplace collaboration and reflection. Sites shared implementation best practices and outcomes. Cross-site evaluations of the impacts of these educational strategies indicated improvements in trainee clinical knowledge, team-based approaches to care and interest in primary care careers. Improved patient outcomes were seen in the quality of chronic disease management, reduction in polypharmacy, and reduced emergency department and hospitalizations. Evaluations of the culture of training environments demonstrated incorporation and persistence of interprofessional learning and collaboration. CONCLUSIONS: Aligning education and practice goals with cross-site collaboration created a robust interprofessional learning environment. Improved trainee/staff satisfaction and better patient care metrics supports use of this model to transform ambulatory care training. TRIAL REGISTRATION: This evaluation was categorized as an operation improvement activity by the Office of Academic Affairs based on Veterans Health Administration Handbook 1058.05, in which information generated is used for business operations and quality improvement (Title 38 Code of Federal Regulations Part 16 (38 CFR 16.102(l)). The overall project was subject to administrative oversight rather Human Subjects Institutional Review Board, as such informed consent was waived as part of the project implementation and evaluation.

Stimuli-responsive magnetic silica-poly-lactic-co-glycolic acid hybrid nanoparticles for targeted cancer chemo-immunotherapy.

Chemotherapy and immunotherapy are two important modalities in cancer management. However, due to multiple reasons, a monotherapy is only partially effective. Hence, if used concurrently in targeted and stimuli-responsive manner, it could have been superior therapeutically. To facilitate co-delivery of chemotherapeutic and immunotherapeutic agent to the target cancer cells, engineered nanoparticles, i.e., a pH-responsive polymer PLGA-coated magnetic silica nanoparticles (Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs) encapsulating paclitaxel (PTX) and siRNA against programmed cell death ligand-1 (PD-L1) are synthesized and characterized. Developed nanoparticles demonstrated pH-sensitive sustained drug release up to 10 days. In vitro 4T1 cell line studies showed efficient cellular uptake, PD-L1 gene downregulation, and apoptosis. Further, in vivo efficacy studies carried out in the mice model demonstrated a significant reduction of tumor growth following treatment with dual-Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs as compared with monotherapy with Fe3O4-SiO2-PLGA-PDA-PTX NPs. The high therapeutic efficacy observed with dual-Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs was mainly due to the cytotoxic effect of PTX combined with targeted silencing of the gene of interest, i.e., PD-L1, which in turn improve CD8+ T cell-mediated cancer cell death as evident with increased proliferation of CD8+ T cells in co-culture experiments. Thereby, dual-Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs may have a promising anti-cancer treatment potential against breast cancer; however, the beneficial effects of dual loading of PTX + PD-L1 siRNA may be corroborated against other cancer models such as lung and colorectal cancer models as well as in clinical trials.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Therapeutic Potential of Cornus Genus: Navigating Phytochemistry, Pharmacology, Clinical Studies, and Advanced Delivery Approaches.

The genus Cornus (Cornaceae) plants are widely distributed in Europe, southwest Asia, North America, and the mountains of Central America, South America, and East Africa. Cornus plants exhibit antimicrobial, antioxidative, antiproliferative, cytotoxic, antidiabetic, anti-inflammatory, neuroprotective and immunomodulatory activities. These plants are exploited to possess various phytoconstituents such as triterpenoids, iridoids, anthocyanins, tannins and flavonoids. Pharmacological research and clinical investigations on various Cornus species have advanced significantly in recent years. Over the past few decades, a significant amount of focus has also been made into developing new delivery systems for Cornus mas and Cornus officinalis. This review focuses on the morphological traits, ethnopharmacology, phytochemistry, pharmacological activities and clinical studies on extracts and active constituents from plants of Cornus genus. The review also highlights recent novel delivery systems for Cornus mas and Cornus officinalis extracts to promote sustained and targeted delivery in diverse disorders. The overwhelming body of research supports the idea that plants from the genus Cornus have therapeutic potential and can be investigated in the future for treatingseveral ailments.

Safety and efficacy of N-acetylcysteine (NAC) as an adjunct to standard treatment in patients with acute ischemic stroke: a randomized controlled pilot trial (NACTLYS).

There is a pressing clinical need for thrombolytic agents that can effectively disaggregate arterial thrombi in acute ischemic stroke without significantly increasing the risk of bleeding. This pilot study aimed to investigate the safety and efficacy of N-acetylcysteine (NAC) as an adjunctive therapy to intravenous recombinant tissue plasminogen activator (rtPA or alteplase). A randomized, open-label, blinded assessor pilot study was conducted. Patients presenting with an acute ischemic stroke within 4.5 h from onset were randomized into two groups: intravenous NAC and rtPA or rtPA alone. Primary outcomes included intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes comprised major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24 h, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24 h, modified Rankin scale, and three-month mortality. Forty patients were enrolled, with 21 receiving only rtPA and 19 receiving NAC with rtPA. Baseline characteristics were comparable among groups. No significant differences were observed in adverse events (p = 0.99), intracranial hemorrhage (p = 0.21), symptomatic intracerebral hemorrhage (p = 0.47), or extracranial bleeding (p = 0.21). Median NIHSS at 24 h was significantly lower in the intervention group (p = 0.03). Functional outcomes and three-month mortality were similar between groups (p = 0.85 and p = 0.99 respectively). The co-administration of N-acetylcysteine with alteplase did not significantly alter safety profiles, morbidity, or mortality at 3 months. While no substantial differences were noted, a slightly improved early neurological outcome was observed in the intervention arm. The study's findings were constrained by a small sample size, emphasizing the necessity for future large-scale trials to comprehensively evaluate the safety and efficacy of N-acetylcysteine as a thrombolytic agent in acute ischemic stroke.Trial Registration Clinical Trials Registry India-CTRI/2019/05/019305.

A bis-quinoline ruthenium(II) arene complex with submicromolar cytotoxicity in castration-resistant prostate cancer cells.

A new Ru(II) arene chlorido organometallic complex [(η6-p-cymene)(L)RuCl]PF6 (named as pCYRuL) using 2-bis(quinolin-2-ylmethylene) hydrazine (L) was developed that exhibits potent anticancer activity against castration-resistant prostate cancer (CRPC) (IC50 = 0.71 µM), and it is 45 times more effective than the standard drug cisplatin (IC50 = 31.3 µM) in a castration-resistant human prostatic adenocarcinoma cell line (PC-3) but non-toxic in normal human kidney cells (HK2) as well as normal breast cells (MCF10A) and found that pCYRuL exerted anticancer activity via apoptosis induction and cell cycle arrest in the G2/M phase of PC-3 cells.

Comprehensive Outcome Assessment and Quality of Life Following Epilepsy Surgery.

BACKGROUND: Seizure freedom without deficits is the primary goal for epilepsy surgery. However, patients with medically refractory epilepsy commonly suffer from many co-morbidities related to mood, cognition, and sleep as well as social problems and resultant stigma. While epilepsy surgery literature does describe quality of life (QOL) and neuropsychological outcomes, there is a paucity of information on various common non-seizure outcomes, especially pertaining to mood, sleep, cognition, and social aspects. The objective of this study was to evaluate the role of various non-seizure parameters on post-epilepsy surgery QOL. METHODS: Consecutive adult patients operated for refractory epilepsy at least 1 year prior to initiation of this study were included and classified as seizure-free (group 1) or non-seizure-free (group 2). QOL was assessed using the QOLIE-31 instrument; patients with a T score less than 40 were categorized as "poor QOL." Non-seizure parameters assessed were cognition, mood disturbances, social improvement, social stigma, and sleep disturbances. Categorization into "good" and "poor" outcome subgroups on each item was carried out by dichotomization of scores. RESULTS: Thirty-seven patients (16 F) [mean age 23.5 ± 5.6 years] were evaluated; 26 were seizure-free (group 1). In this group, impaired memory, lower language scores, depression, not having been employed, not receiving education prior to surgery, and experiencing social stigma were factors significantly associated with poor QOL. In group 2, all patients had poor QOL scores. CONCLUSION: Non-seizure factors related to common epilepsy co-morbidities and social issues are highly prevalent among seizure-free patients reporting poor QOL after epilepsy surgery.

Diversity of Linum genetic resources in global genebanks: from agro-morphological characterisation to novel genomic technologies - a review.

Linseed or flaxseed is a well-recognized nutritional food with nutraceutical properties owing to high omega-3 fatty acid (α-Linolenic acid), dietary fiber, quality protein, and lignan content. Currently, linseed enjoys the status of a 'superfood' and its integration in the food chain as a functional food is evolving continuously as seed constituents are associated with lowering the risk of chronic ailments, such as heart diseases, cancer, diabetes, and rheumatoid arthritis. This crop also receives much attention in the handloom and textile sectors as the world's coolest fabric linen is made up of its stem fibers which are endowed with unique qualities such as luster, tensile strength, density, bio-degradability, and non-hazardous nature. Worldwide, major linseed growing areas are facing erratic rainfall and temperature patterns affecting flax yield, quality, and response to biotic stresses. Amid such changing climatic regimes and associated future threats, diverse linseed genetic resources would be crucial for developing cultivars with a broad genetic base for sustainable production. Furthermore, linseed is grown across the world in varied agro-climatic conditions; therefore it is vital to develop niche-specific cultivars to cater to diverse needs and keep pace with rising demands globally. Linseed genetic diversity conserved in global genebanks in the form of germplasm collection from natural diversity rich areas is expected to harbor genetic variants and thus form crucial resources for breeding tailored crops to specific culinary and industrial uses. Global genebank collections thus potentially play an important role in supporting sustainable agriculture and food security. Currently, approximately 61,000 germplasm accessions of linseed including 1,127 wild accessions are conserved in genebanks/institutes worldwide. This review analyzes the current status of Linum genetic resources in global genebanks, evaluation for agro-morphological traits, stress tolerance, and nutritional profiling to promote their effective use for sustainable production and nutrition enhancement in our modern diets.

Role of corneal collagen cross-linking in bullous keratopathy: A systematic review.

Corneal cross-linking (CXL), a corneal strengthening procedure, is known to alter anterior stroma swelling behavior and is one of the treatment modalities of bullous keratopathy (BK). There are multiple studies published on the role of CXL in the treatment of BK. These articles had heterogeneous study population, different protocols used, and variable conclusions. This systematic review aimed to determine the role of CXL in the treatment of BK. The primary outcomes considered were changes in central corneal thickness (CCT) after 1, 3, and 6 months of CXL. The secondary outcome measures were changes in visual acuity, corneal clarity, subjective symptoms, and complications after CXL. We included randomized control trials (RCTs), observational and interventional studies, and case series with reports of more than 10 cases in this review. In RCTs, the mean pre-CXL CCT (794.0 ± 178.5 µm) in the intervention group (n = 37), decreased at 1 month (750.9 ± 154.3 µm) followed by a subsequent increase, but this difference was not significant during the 6-month follow-up (P- value 0.28, 0.82, and 0.82 at 1, 3, and 6 months, respectively). In noncomparative clinical studies (n = 188), the mean pre-CXL CCT (794.0 ± 178.5 µm) decreased at 1 month (710.9 ± 127.2 µm, P < 0.0001). Seven of the 11 articles included in the review reported no significant improvement in vision with CXL. The initial improvement in corneal clarity and clinical symptoms was not sustained. Current evidence suggests that CXL has short-term efficacy in the treatment of BK. More RCTs with high-quality evidence are needed.

Design and Synthesis of Thiazole Scaffold-Based Small Molecules as Anticancer Agents Targeting the Human Lactate Dehydrogenase A Enzyme.

A new series of thiazole central scaffold-based small molecules of hLDHA inhibitors were designed using an in silico approach. Molecular docking analysis of designed molecules with hLDHA (PDB ID: 1I10) demonstrates that Ala 29, Val 30, Arg 98, Gln 99, Gly 96, and Thr 94 possessed strong interaction with the compounds. Compounds 8a, 8b, and 8d showed good binding affinity (-8.1 to -8.8 kcal/mol), whereas an additional interaction of NO2 at the ortho position in compounds 8c with Gln 99 through hydrogen bonding enhanced the affinity to -9.8 kcal/mol. Selected high-scored compounds were synthesized and screened for hLDHA inhibitory activities and in vitro anticancer activity in six cancer cell lines. Biochemical enzyme inhibition assays showed the highest hLDHA inhibitory activity observed with compounds 8b, 8c, and 8l. Compounds 8b, 8c, 8j, 8l, and 8m depicted significant anticancer activities, exhibiting IC50 values in the range of 1.65-8.60 µM in HeLa and SiHa cervical cancer cell lines. Compounds 8j and 8m exhibited notable anticancer activity with IC50 values of 7.90 and 5.15 µM, respectively, in liver cancer cells (HepG2). Interestingly, compounds 8j and 8m did not induce noticeable toxicity in the human embryonic kidney cells (HEK293). Insilico absorption, distribution, metabolism, and excretion profiling demonstrates that the compounds possess drug-likeness, and results may pave the way for the development of novel thiazole-based biologically active small molecules for therapeutics.

Ocular manifestations of common pulmonary diseases: a narrative review.

Several pulmonary disorders can cause ocular involvement. Understanding these manifestations is critical for early diagnosis and treatment. Hence, we set out to examine the most common ocular manifestations of asthma, chronic obstructive pulmonary disease (COPD), sarcoidosis, obstructive sleep apnea (OSA), and lung cancer. Allergic keratoconjunctivitis and dry eye are two ocular manifestations of bronchial asthma. The inhaled corticosteroids used to treat asthma can cause cataract formation. COPD is associated with ocular microvascular changes as a result of chronic hypoxia and systemic inflammation spillover into the eyes. Its clinical significance, however, is unknown. Ocular involvement is common in sarcoidosis, occurring in 20% of cases of pulmonary sarcoidosis. It can affect nearly any anatomical structure of the eye. Obstructive sleep apnea has been linked to floppy eye syndrome, glaucoma, non-arteritic anterior ischemic optic neuropathy, keratoconus, retinal vein occlusion, and central serous retinopathy, according to research. However, while an association has been established, causality has yet to be established. The effect of positive airway pressure (PAP) therapy used to treat OSA on the aforementioned ocular conditions is unknown. PAP therapy can cause eye irritation and dryness. Lung cancer can affect the eyes through direct nerve invasion, ocular metastasis, or as part of a paraneoplastic syndrome. The goal of this narrative review is to raise awareness about the link between ocular and pulmonary disorders in order to aid in the early detection and treatment of these conditions.

Randomized double-blind, placebo-controlled study of oral gabapentin for prevention of neuropathy in patients receiving paclitaxel.

BACKGROUND: Peripheral neuropathy is a common dose-limiting side effect of paclitaxel. To date, there is no effective strategy to prevent paclitaxel-induced peripheral neuropathy. A recent small phase II study demonstrated the potential role of oral gabapentin in this setting. This phase III study is aimed to assess the efficacy of oral gabapentin in preventing paclitaxel-induced neuropathy. OBJECTIVE: To compare the efficacy of oral gabapentin with placebo in preventing clinically significant peripheral neuropathy (NCI CTCAEv5.0 grade 2 or higher) in patients receiving paclitaxel. METHODS: This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial. The primary outcome is the development of grade 2 or higher chemotherapy-induced peripheral neuropathy. Secondary outcomes include any grade neuropathy, the percentage change in sensory nerve conduction velocities in peripheral nerves, time to development of any grade neuropathy, paclitaxel dose reductions and delays due to peripheral neuropathy, patient-reported outcomes, adverse events, and adherence to oral therapy. A total of 136 patients receiving paclitaxel will be randomly allocated (stratified by weekly vs. non-weekly administration) to receive either oral gabapentin or placebo till three weeks after the last dose of chemotherapy or occurrence of the primary outcome. CONCLUSION: This study aims to find if oral gabapentin reduces the incidence of grade 2 or higher chemotherapy-induced peripheral neuropathy in patients receiving paclitaxel. TRIAL REGISTRATION: The trial is registered prospectively with the Clinical Trials Registry of India (CTRI/2022/02/040030) on April 4, 2022.

Targeting monocarboxylate transporters (MCTs) in cancer: How close are we to the clinics?

As a result of metabolic reprogramming, cancer cells display high rates of glycolysis, causing an excess production of lactate along with an increase in extracellular acidity. Proton-linked monocarboxylate transporters (MCTs) are crucial in the maintenance of this metabolic phenotype, by mediating the proton-coupled lactate flux across cell membranes, also contributing to cancer cell pH regulation. Among the proteins codified by the SLC16 gene family, MCT1 and MCT4 isoforms are the most explored in cancers, being overexpressed in many cancer types, from solid tumours to haematological malignancies. Similarly to what occurs in particular physiological settings, MCT1 and MCT4 are able to mediate lactate shuttles among cancer cells, and also between cancer and stromal cells in the tumour microenvironment. This form of metabolic cooperation is responsible for important cancer aggressiveness features, such as cell proliferation, survival, angiogenesis, migration, invasion, metastasis, immune tolerance and therapy resistance. The growing understanding of MCT functions and regulation is offering a new path to the design of novel inhibitors that can be foreseen in clinical practices. This review provides an overview of the role of MCT isoforms in cancer and summarizes the recent advances in their pharmacological targeting, highlighting the potential of new potent and selective MCT1 and/or MCT4 inhibitors in cancer therapeutics, and anticipating its inclusion in clinical practice.

G-quadruplex-mediated specific recognition, stabilization and transcriptional repression of bcl-2 by small molecule.

The presence of the G-quadruplex (G4) structure in the promoter region of the human bcl-2 oncogenes makes it a promising target for developing anti-cancer therapeutics. Bcl-2 inhibits apoptosis, and its frequent overexpression in cancer cells contributes to tumor initiation, progression, and resistance to therapy. Small molecules that can specifically bind to bcl-2 G4 with high affinity and selectivity are remaining elusive. Here, we report that small molecule 1,3-bis-) furane-2yl-methylidene-amino) guanidine (BiGh) binds to bcl-2 G4 DNA structure with very high affinity and selectivity over other genomic G4 DNA structures and duplex DNA. BiGh stabilizes folded parallel conformation of bcl-2 G4 via non-covalent and electrostatic interactions and increases the thermal stabilization up to 15 °C. The ligand significantly suppresses the bcl-2 transcription in HeLa cells by a G4-dependent mechanism and induces cell cycle arrest which promotes apoptosis. The in silico ADME profiling confirms the potential 'drug-likeness' of BiGh. Our results showed that BiGh stabilizes the bcl-2 G-quadruplex motif, downregulates the bcl-2 gene transcription as well as translation process in cervical cancer cells, and exhibits potential anti-cancer activity. This work provides a potential platform for the development of lead compound(s) as G4 stabilizers with drug-like properties of BiGh for cancer therapeutics.

Role of LDH in tumor glycolysis: Regulation of LDHA by small molecules for cancer therapeutics.

Lactate dehydrogenase (LDH) is one of the crucial enzymes in aerobic glycolysis, catalyzing the last step of glycolysis, i.e. the conversion of pyruvate to lactate. Most cancer cells are characterized by an enhanced rate of tumor glycolysis to ensure the energy demand of fast-growing cancer cells leading to increased lactate production. Excess lactate creates extracellular acidosis which facilitates invasion, angiogenesis, and metastasis and affects the immune response. Lactate shuttle and lactate symbiosis is established in cancer cells, which may further increase the poor prognosis. Several genetic and phenotypic studies established the potential role of lactate dehydrogenase A (LDHA) or LDH5, the one homo-tetramer of subunit A, in cancer development and metastasis. The LDHA is considered a viable target for drug design and discovery. Several small molecules have been discovered to date exhibiting significant LDHA inhibitory activities and anticancer activities, therefore the starvation of cancer cells by targeting tumor glycolysis through LDHA inhibition with improved selectivity can generate alternative anticancer therapeutics. This review provides an overview of the role of LDHA in metabolic reprogramming and its association with proto-oncogenes and oncogenes. This review also aims to deliver an update on significant LDHA inhibitors with anticancer properties and future direction in this area.

Exopolyphosphatases PPX1 and PPX2 from Mycobacterium tuberculosis regulate dormancy response and pathogenesis.

Stress adaptation and virulence of various bacterial pathogens require stringent response pathways involving guanosine pentaphosphate and inorganic polyphosphate (PolyP). In M. tuberculosis, intracellular PolyP levels are maintained by the activities of polyphosphate kinase (PPK-1, PPK-2) and exopolyphosphatases (PPX-1, PPX-2). We demonstrate that these exopolyphosphatases cumulatively contribute to biofilm formation and survival of M. tuberculosis in nutrient limiting, low oxygen growth conditions and in macrophages. Characterization of single (Δppx2) and double knock out strain (dkppx) of M. tuberculosis demonstrated that these exopolyphosphatases are essential for establishing infection in guinea pigs and mice. Transcriptional profiling revealed that relative to the parental strain the expression of genes belonging to DosR regulon were significantly reduced in mid-log phase cultures of dkppx strain. We also show that PolyP inhibited the autophosphorylation activities associated with DosT and DosS sensor kinases. Host RNA-seq analysis revealed that transcripts involved in various antimicrobial pathways such as apoptosis, autophagy, macrophage activation, calcium signalling, innate and T-cell response were differentially expressed in lung tissues of dkppx strain infected mice. Taken together, we demonstrate that enzymes involved in PolyP homeostasis play a critical role in physiology and virulence of M. tuberculosis. These enzymes are attractive targets for developing novel interventions that might be active against drug-sensitive and drug-resistant M. tuberculosis.

Study Protocol: IMPETUS: Implementing a Uniform Stroke Care Pathway in Medical Colleges of India: IMPETUS Stroke.

Introduction: In India, a national program for stroke (national programme for the control of cardiovascular diseases, diabetes, cancer, and stroke) and stroke management guidelines exist. Its successful implementation would need an organized system of stroke care in practice. However, many challenges exist including lack of awareness, prehospital notification systems, stroke ready hospitals, infrastructural weaknesses, and rehabilitation. We present here a protocol to investigate the feasibility and fidelity of implementing a uniform stroke care pathway in medical colleges of India. Methods and Analysis: This is a multicentric, prospective, multiphase, mixed-method, quasi-experimental implementation study intended to examine the changes in a select set of stroke care-related indicators over time within the sites exposed to the same implementation strategy. We shall conduct process evaluation of the implementation process as well as evaluate the effect of the implementation strategy using the interrupted time series design. During implementation phase, education and training about standard stroke care pathway will be provided to all stakeholders of implementing sites. Patient-level outcomes in the form of modified Rankin Scale score will be collected for all consecutive patients throughout the study. Process evaluation outcomes will be collected and reported in the form of various stroke care indicators. We will report level and trend changes in various indicators during the three study phases. Discussion: Acute stroke requires timely detection, management, and secondary prevention. Implementation of the uniform stroke care pathway is a unique opportunity to promote the requirements of homogenous stroke care in medical colleges of India.

Corneal endothelial protection during manual small-incision cataract surgery: A narrative review.

Cataract causes bilateral blindness in 20 million people globally, the vast majority of whom live in developing countries. Manual small-incision cataract surgery (MSICS) has emerged as an efficient and economical alternative to phacoemulsification, giving comparable results in terms of final visual gain. One of the important determinants of postoperative visual gain is the status of the corneal endothelium. Multiple factors such as corneal distortion, irrigation solution turbulence, mechanical trauma by instruments, nuclear fragments, intraocular lens contact, and free oxygen radicals, all have been implicated in causing corneal damage during cataract surgery. MSICS with posterior chamber intraocular lens implantation has been reported to cause an endothelial cell loss of 15.83%, which is comparable with other modes of cataract surgery like extracapsular cataract extraction and phacoemulsification. Thorough preoperative assessment of endothelial status and taking necessary steps for endothelial protection during surgery can decrease the endothelial cell loss and overall burden of pseudophakic bullous keratopathy. In addition to surgical techniques, the type of irrigating solutions, ocular viscoelastic devices, intracameral dyes, and drugs all affect the endothelial cell status. This review presents a summary of available literature on the protection of endothelial cells during different steps of MSICS. This is especially relevant for developing countries where large-scale MSICS cataract surgeries are performed to decrease the cataract blindness burden.

A Comparative Analysis of Nondescent Vaginal Hysterectomy, Laparoscopy-Assisted Vaginal Hysterectomy, and Total Laparoscopic Hysterectomy for Benign Uterine Diseases at a Rural Tertiary Care Center.

Objectives: The aim of this study was to compare operative data and postoperative complications among nondescent vaginal hysterectomy (NDVH), laparoscopy-assisted vaginal hysterectomy (LAVH), and total laparoscopic hysterectomy (TLH) at a rural tertiary care center. Materials and Methods: This is a prospective analytical study, of 145 hysterectomies for benign conditions with or without salpingo-oophorectomy in women from 30 to 60 years, over 3 years from January 2016 to December 2019, with 60 cases of NDVH, 46 cases of LAVH, and 39 cases of TLH. The three groups were compared intraoperatively in terms of blood loss, operating time, and intraoperative complications and postoperative complications and postoperative duration of hospital stay. Results: There was no significant difference between the three groups in terms of age, parity, body mass index, and indications for hysterectomies. The mean operative time was significantly shorter (P = 0.000) in the NDVH group (54.67 ± 15.67 min) as compared to the LAVH (102.45 ± 10.53 min) and TLH (126.79 ± 8.7 min) groups. Intraoperative blood loss was greater (P = 0.000) in the TLH group (111.025 mL ± 20.8) as compared to the NDVH (59.50 mL ± 16.7) and LAVH (91.85 mL ± 10.66) groups. The intraoperative complications and postoperative complications were higher in the TLH group as compared to the LAVH and NDVH groups. The duration of hospital stay was almost similar in all the groups. Conclusion: NDVH may be the preferred approach for experienced surgeons, as it is less time-consuming, has a small amount of blood loss, and is a scarless surgery, whereas LAVH and TLH may be the preferred approaches in the cases of presence of adnexal masses and adhesions or whenever salpingo-oophorectomy is indicated.