bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors affecting students’ use of blended learning during coronavirus disease 2019 pandemic at Assiut University, Egypt
Authors: Khalaf Shimaa Abdelrahim , Mahmoud Ghada Abdelrahman , Elmagd Nahed Sh Abo , Ahmed Zamzam Ahmed , Aly Shimaa El-Wardany
Published: May 2024

Background

Blended learning forms the natural evolution of learning in the contemporary time to cope with current challenges to meet the educational needs of students.

Objectives

To determine the factors that affect students’ use of blended learning during coronavirus disease 2019 at Assiut University.

Study design

Descriptive cross-sectional.

Settings

Ten colleges that were selected by simple random sampling from each sector (medical and nonmedical).

Participants

One thousand six hundred forty university students.

Patients and methods

One tool divided into two parts: part I: student personal data; part II: scale to examine the factors influencing blended learning use.

Results

Lecturer’s factor had the high moderate mean±SD 3.11±0.95, followed by technical support 3.00±0.99, while usability and information quality with low medium mean±SD (2.87±0.99 and 2.87±0.96, respectively). Also, there was statistically significance differences between factors influencing blended learning use and college type, age of students, and class with P value of 0.000.

Conclusion

Factors of lecturers, technical support, and information quality had valuable effect on the university students’ use of blended learning.

Recommendation

The university staff should encourage their students to use blended learning as a preferable approach for enhancing their interaction and communication skills.
Effect of maternal partnership discharge program on mothers’ knowledge and selected health outcomes of their preterm infants
Authors: Mohamed Hanem Abdallah , Abo-Seif Lareen Magdi El-Sayed , Machaly Eslam Reda
Published: May 2024

Background Discharge of preterm infants from neonatal intensive care unit (NICU) is a stressful experience for mothers as they will have to resume the full responsibility of their care for the first time, and without discharge preparation, it is even more stressful for them. Even though western research studies have showed positive effects of family-centered care (FCC) and parent/mother partnership programs for preterm mothers on maternal confidence in care provision and reflected on preterm health status, there is still a need to study its effectiveness in Arab countries.

Aim To evaluate the effect of maternal partnership discharge program on mothers’ knowledge and selected health outcomes of their preterm infants.
Prediction of outcomes among mechanically ventilated patients with acute traumatic brain injury
Authors: Ashour Saleh Ibrahim Atta , Mohammed Morsy Warda Youssef , Hassan El-Sharkawy Fatma Mohktar , Seloma Yousria Abd El- Salam
Published: May 2024

Background

Literature review cites that traumatic brain injury (TBI) worldwide is rising, mainly owing to injuries associated with the increased use of motor vehicles. TBI is a serious public health problem in Egypt. Although the Glasgow coma scale (GCS) is the most commonly used scale, the Full Outline of Unresponsiveness (FOUR) scale is a new coma scale as an alternative to GCS in the evaluation of the level of consciousness.

Aim

To compare the predicted outcomes among mechanically ventilated patients with acute TBI using the GCS and the FOUR scale.

Research design

A descriptive comparative design was used to achieve the aim of the study.

Setting

The study was conducted in one of the ICUs of Cairo University Hospitals.

Patients and methods

A purposive sample of 124 critically ill adult patients connected to mechanical ventilators and diagnosed as having acute TBI was used.

Tools of data collection

Three tools were used: tool I, an assessment form for patients with mechanically ventilated acute TBI; tool II, GCS, and tool III, FOUR scale.

Results

The mean age of the study sample was 29.02±3.41 years, 80.6% were males, and majority of them had road traffic accident as the cause of injury. There was a significant statistical difference between GCS and FOUR with respect to duration/days of connection to mechanical ventilation [GCS (P=0.000) and FOUR (P=0.001)]; no complications (P=0.000); seizure (P=0.000); meningitis (P=0.017); and seizure, brain edema, meningitis, and cerebral hemorrhage (P=0.000).

Conclusion

High sensitivity and specificity of the FOUR scale for patients’ outcomes (death/survival) were documented in comparison with the GCS.

Recommendation

Further studies have to be carried out to compare FOUR scale with other tools among a larger probability sample in different geographical locations on a national level.
Effect of cold application on intramuscular injection pain among patients with fractures
Authors: Mahmoud Hager S. , Abdel Aziz Salwa H. , Ibrahim Mishmisha E.
Published: May 2024

Background

Intramuscular injection (IMI) is an invasive and painful procedure that is routinely used in health care settings. The knowledge regarding the efficiency of nonpharmacological methods of pain management, including cold application, is limited and needs further research studies.

Aim

The aim of the study was to evaluate the effect of cold application on IMI pain among patients with fractures.

Design

A quasi-experimental design (pre-posttest nonequivalent control group design) was used.

Setting

This study was conducted in the inpatient clinic of Orthopedic Surgical Department in Beni Suef University Hospital.

Sample

A convenient consecutive sample of 64 adult male and female patients was enrolled in the study.

Tools

Two tools were used for data collection: (a) structured interview assessment form, including sociodemographic and medical-related data, and (b) pain assessment forms.

Results

The study findings revealed that the mean age of the study and control groups was 39.2±11.1 and 34.8±11.9 years, respectively. When analyzing the numerical pain scale, a statistically significant difference was found between both groups, with higher reduction in the total mean score of pain from 6.78±1.6 to 2.34±0.9 among the group that received cold application before IMI. It also showed that there were highly statistically significant differences in the total mean score of the observational checklist of nonverbal pain indicators of the study group between preintervention and postintervention results during movement and at rest (P≤0.001).

Conclusion

This study concluded that cold application was an effective nursing measure in reducing the pain intensity associated with IMI.

Recommendations

Continuous education for nurses must be provided to improve their knowledge and practice regarding nonpharmacological methods such as cold application and its effect on relieving pain arising from IMI into the vastus lateralis muscle.
Staff nurse’s perception about performance-appraisal fairness and its relation to their work engagement
Authors: Hamdeen Marwa S. , Elewa Amal H. , Mohamed Salwa A.
Published: May 2024

Background

An organization’s performance-appraisal system can be a practical tool for employee engagement, motivation, and development when employees perceive their performance appraisals as fair.

Aim

To assess staff nurses’ perception about performance-appraisal fairness and its relation to their work engagement at Beni-Suef University Hospital.

Design

A descriptive correlational design was utilized.

Setting

Data were collected from Beni-Suef University Hospital.

Sample

A convenient sample (n=250) of staff nurses who accepted to participate in the study.

Tools

Two tools were utilized to collect data: (a) performance-appraisal fairness perception questionnaire, (2) Utrecht Work Engagement Scale.

Results

The results of the study revealed that the majority of staff nurses highly perceived all domains of performance appraisal, interpersonal justice mean-percent score was 86.2% and distributive justice was 79.4%. They also had a high perception of work engagement, with a mean-percent score of 89.5% for the dedication domain, followed by vigor (83.7%) and absorption domain (82.7%). More than two-thirds of staff nurses (67.6%) reported high levels of work engagement, and there was a statistically significant positive correlation between total (r: 0.370, P: 0.00) and all domains of performance-appraisal fairness and work engagement.

Conclusion

The study findings concluded that staff nurses highly perceived performance-appraisal fairness and work engagement, more than two-thirds of staff nurses had high levels of work engagement, and there was a statistically highly significant positive correlation between staff nurses’ perception of performance-appraisal fairness and their work engagement. Recommendations: the administrator should develop a plan for continuous improvement of performance-appraisal fairness, continuous training of head nurses on how to perform sound performance appraisals, regularly revise, update, and disseminate performance-appraisal forms, suggest a plan to sustain a high level of engagement, and motivate staff to participate in performance-appraisal planning to be more engaged.
Study of fingolimod, nitric oxide inhibitor, and P-glycoprotein inhibitor in modulating the P-glycoprotein expression via an endothelin–sphingolipid pathway in an animal model of pharmacoresistant epilepsy
Authors: Garg Nitika , Joshi Rupa , Bhatia Alka , Bansal Seema , Chakrabarti Amitava , Prakash Ajay , Saikia Biman , Modi Manish , Medhi Bikash
Published: May 2024

BACKGROUND:

The overexpression of P-glycoprotein (P-gp) contributes to drug resistance in patients with epilepsy, and the change of P-gp expression located at the blood–brain barrier alienates the anti-seizure effects of P-gp substrates. Thus, the present study explored the effect of fingolimod (FTY720) acting through an endothelin–sphingolipid pathway on P-gp-induced pentylenetetrazol (PTZ)-kindled phenobarbital (PB)-resistant rats.

MATERIALS AND METHODS:

PTZ kindling (30 mg/kg; i.p.) and PB (40 mg/kg; orally) were used to develop an animal model of refractory epilepsy. The effect of Fingolimod on seizure score (Racine scale), plasma and brain levels of PB (high-performance liquid chromatography), and blood–brain barrier permeability (Evans blue dye) was determined. Further, Fingolimod's neuroprotective effect was determined by measuring the levels of various inflammatory cytokines, oxidative stress parameters, and neurotrophic factors in rat brain homogenate. The Fingolimod's effect on P-gp expression was estimated by reverse transcriptase–polymerase chain reaction and immunohistochemistry in rat brain. The H and E staining was done to determine the neuronal injury.

RESULTS:

Fingolimod significantly (P < 0.001) reduced the seizure score in a dose-dependent manner and alleviated the blood–brain barrier permeability. It decreased the P-gp expression, which further increased the brain PB concentration. Fingolimod significantly (P < 0.01) reduced oxidative stress as well as inflammation. Moreover, it attenuated the raised neuronal injury score in a resistant model of epilepsy.

CONCLUSION:

The modulation of the P-gp expression by Fingolimod improved drug delivery to the brain in an animal model of refractory epilepsy. Therefore, S1P signaling could serve as an additional therapeutic target to overcome refractoriness.
Efficacy and safety of oral insulin versus placebo for patients with diabetes mellitus
Authors: Dharadhar Saili , Sharma Amit , Dey Debasis
Published: May 2024

OBJECTIVE:

Compliance to insulin injections is poor due to difficulty in subcutaneous administration. Hence, there is a need of an oral formulation of insulin. Oral insulin is currently under investigation. The present analysis aimed to evaluate oral insulin versus placebo for patients with diabetes mellitus (type-1 and type-2).

MATERIALS AND METHODS:

Results from PUBMED and MEDLINE were searched and compiled from January 1, 2000 to January 9, 2020. Postprandial blood glucose excursions (2PPG), glycated hemoglobin (HbA1c), C-peptide levels, and immune antibody (IAA) levels were compared between the arms. In addition, time to diabetes and safety of oral insulin were discussed.

RESULTS:

Thirteen out of 1778 trials were included to the analysis. Oral insulin was found to induce significant reduction in mean 2PPG excursion (standardized mean difference [SMD]: −1.94, 95% CI: −3.20 to −0.68, I
2 = 91.81, P < 0.005) and mean IAA levels (SMD:-0.49, 95% CI: −0.82 to -0.16, I
2 = 27.12, P < 0.005) compared with placebo. Mean C-peptide levels were notably lower in the oral insulin arm. However, the difference was not statistically significant. No significant difference was observed in mean HbA1c levels. The rate of development of type-1 diabetes was not significantly influenced by oral insulin. No deaths or treatment-related serious adverse events were reported.

CONCLUSION:

Oral insulin provided significant benefits for acute maintenance of diabetes mellitus. It elicited lower immune response and was well tolerated. This new formulation has potential to augment the management of diabetes mellitus. More studies are required to assess its long-term effects.
Role of intravenous aspirin versus oral aspirin in the treatment of acute coronary syndrome
Authors: Kaur Hardeep , Sarma Phulen , Bhattacharyya Anusuya , Rohit Manojkumar , Prajapat Manisha , Kumar Subodh , Prakash Ajay , Medhi Bikash
Published: May 2024

BACKGROUND:

Aspirin is indicated in the emergency management of acute coronary syndrome. However, oral aspirin has erratic bioavailability compared to i.v. formulation.

OBJECTIVE:

The objective of this study was to evaluate the comparative efficacy and safety of intravenous (IV) and oral aspirin in acute coronary syndrome.

STUDY DESIGN:

This was a systematic review and meta-analysis.

RESULTS:

Two randomized controlled trials were included. Compared to oral aspirin, lower platelet aggregability was seen with IV aspirin at 5 min and 20 min. Lower thromboxane B2 and lower platelet CD-62p levels were noted in the IV group; however, no significant difference was observed in terms of “composite cardiovascular death, stroke, and myocardial infarction (MI) at 4–6 weeks,” “any cause mortality,” “cardiovascular mortality,” “occurrence of stroke,” and “occurrence of MI/reinfarction.” However, no difference was noted in terms of the occurrence of serious adverse events.

CONCLUSION:

IV aspirin showed some advantages in terms of platelet aggregability biomarkers at 20 min and 1 week with comparable safety to oral aspirin. No difference was seen in terms of clinical outcomes (at 24 h, 7, and 30 days) and the occurrence of serious adverse events.
Comparative evaluation of efficacy and tolerability of apremilast and methotrexate in patients of moderate-to-severe palmoplantar psoriasis: A randomized, parallel, open-label clinical trial
Authors: Wagh Mitali , Mukhi Jayesh , Sontakke Smita , Dhok Amit , Turankar Avinash , Kalikar Mrunalini
Published: May 2024

BACKGROUND:

Variable results about efficacy as well as safety of apremilast compared to methotrexate are reported in different trials. Hence, it is necessary to collect more evidence to prove the role of Apremilast in palmoplantar psoriasis.

METHODOLOGY:

The study was a randomized, prospective, parallel-group, open-label study conducted in patients with moderate-to-severe palmoplantar psoriasis. They were randomized into two groups, methotrexate (n = 19) or apremilast (22) for 16 weeks. Primary efficacy parameter was reduction in modified palmoplantar psoriasis area and severity index (mPPPASI) score from week 0 to week 16. Other parameters were proportion of patients attaining Static Physician Global Assessment score of 0 (clear) or 1 (almost clear), proportion of patients attaining mPPPASI75 (75% reduction in mPPPASI score) at the end of 16 weeks, and proportion of patients showing at least 5-point decline in dermatology life quality index from baseline.

RESULTS:

Decline in m-PPPASI score from 0 week to 16 weeks within the group was significant statistically though decline in score of m-PPPASI between these two groups was not statistically significant at 16 weeks. Similar results were obtained with the secondary efficacy parameters. In methotrexate group, there were 24 adverse events recorded including abnormal liver function tests in three patients. In apremilast group, 19 adverse events were recorded, in which two patients suffered from upper respiratory tract infection.

CONCLUSION:

Apremilast is as effective as methotrexate for the management of moderate-to-severe palmoplantar psoriasis with better tolerability. Hence, it can be considered alternative to established drugs in patients having palmoplantar psoriasis not responding to or tolerating other drugs.

REGISTRATION:

The study was registered with Clinical Trial Registry of India (CTRI/2020/05/025198).
Pistia stratiotes has renoprotective potentials in ischemia reperfusion injury in normal and diabetic rats
Authors: Bhavsar Vashisth Pankajkumar , Patel Ashish , Vaghasiya Jitendra D. , Padhiyar Shantilal , Patel Tejas B.
Published: May 2024

OBJECTIVE:

Even though oxidative and inflammatory bursts are a big part of renal reperfusion injury (RI/R), Pistia stratiotes (PS) has been used for a long time to stop these overreactions. People have said that it can drop both blood sugar and cholesterol. Hence, the goal of this study was to show how PS changed kidney reperfusion damage in both diabetic and normal rats.

MATERIALS AND METHODS:

In the study, 30 min of renal ischemia (RI) was followed by 1 h of recovery for each rat. Before the test, PS (100 mg/kg p. o.) was given to the animals for 7 days. Then, using the mixture from the separated kidney tissues, the antioxidant, inflammation, and histopathological effects were determined.

RESULTS:

When compared to RI/R, diabetic rats given PS had lower blood sugar, aspartate aminotransferase, blood urea nitrogen, and creatinine, myeloperoxidase, C-reactive protein, and tumor necrosis factor-alpha levels in their urine.

CONCLUSION:

PS potentially worked in hyperglycemic rats protecting them against RI/R. It is possible that PS’s ability to protect the kidneys of the test rats is due to its ability to fight free radicals, lower blood sugar, and stop inflammation.
Drug development process and COVID-19 pandemic
Authors: Wasan Himika , Singh Devendra , Reeta K. H. , Gupta Pooja , Gupta Yogendra Kumar
Published: May 2024

Traditional drug development is a tedious process with involvement of enormous cost and a high attrition rate. Outsourcing drug development services to contract research organizations (CROs) has become an important strategy for cost and risk reduction, capacity building, and data generation. The therapeutic and operational expertise of these CROs has allowed pharmaceutical industry to reduce in-house infrastructure as well as research capacity. Working with specialized CROs has not only increased the rate of success but also the speed of drug discovery process. Small firms with promising molecules but limited resources and large firms interested in diversifying their dimensions are utilizing the services of efficient CROs. Globally, approximately one-third of the drug development processes are now being outsourced and the data generated by the independent third party are well appreciated during regulatory submissions. In this article, we discuss the international and national trends, outsourcing services and models, key considerations while selecting CRO, and benefits and challenges of outsourcing. Further, we discuss how the technical expertise of competent CROs was utilized when traditional ways of conducting clinical trials were disrupted by the COVID-19 pandemic. Taken together, the increasing health-care demands, COVID-19 pandemic or any other such upcoming health crisis, and recent advances in advanced technologies (machine learning and artificial intelligence, etc.) are likely to fuel global CRO market in the coming years.
High-level gentamicin resistance mediated by Aac(6′)-Ie-aph(2”)-Ia gene in Enterococcus species isolated from clinical samples in Northern India
Authors: Das Ayan Kumar , Dudeja Mridu , Kohli Sunil , Ray Pratima , Nandy Shyamasree
Published: May 2024

CONTEXT:

Enterococci are known to cause life-threatening infections which are difficult to treat as the organism harbors innate resistance to many antibiotics and can amass resistance toward many others through plasmid-mediated genetic exchange.

AIMS:

The study evaluates the drug susceptibility profile of various Enterococcus species isolated from various patient specimens submitted for bacteriological analysis and check the incidence of aac(6′) Ie-aph(2”) Ia gene.

SETTING AND DESIGN:

This in vitro cross-sectional study was executed at bacteriology laboratory of a 470 bedded hospital in New Delhi.

MATERIALS AND METHODS:

Drug susceptibility testing was carried out on enterococcal isolates. High-level gentamicin-resistant (HLGR) isolates detected by micro broth dilution assay were then subjected to molecular detection of aac(6′) Ie-aph(2”) Ia gene.

STATISTICAL ANALYSIS USED:

The level of significance was established by Chi-square test.

RESULTS:

Among the 182 enterococcal stains detected, 76.9% were Enterococcus faecalis and 20.3% were Enterococcus faecium. 12.08% strains were vancomycin resistant. 39% expressed resistance toward high-level gentamicin (HLG) and this finding was significantly higher in E. faecium than E. faecalis. HLGR strains expressed a higher degree of resistance to other drugs in contrast to non-HLGR isolates. In 67 out of 71 HLGR isolates the bifunctional gene was detected.

CONCLUSION:

Considerable presence of HLG and vancomycin resistance in the clinical isolates is alarming and should be taken seriously. The study shows high dissemination of aac(6′)-Ie-aph(2”)-Ia gene among Enterococci isolated from the region.
Pharmacovigilance study of amphotericin B for mucormycosis in post-COVID and non-COVID patients at a tertiary care hospital in Eastern India
Authors: Chatterjee Suparna , Bhattacharjee Manjari , Hazra Avijit , Mukhopadhyay Pradip , Ray Biman Kanti , Chatterjee Sayan , Dubey Souvik
Published: May 2024

BACKGROUND:

Mucormycosis is a rare but serious fungal infection which has dramatically increased in post-COVID patients. There is a paucity of safety data on amphotericin B (amphoB) used for mucormycosis treatment.

OBJECTIVES:

The objective of this prospective, observational, active safety surveillance study was to evaluate the safety profile of amphoB in a cohort of hospitalized patients who were on the drug for suspected mucormycosis.

MATERIALS AND METHODS:

All suspected adverse drug reactions (ADRs) in hospitalized mucormycosis patients who had received amphoB were analyzed. The nature, severity, outcome of the ADRs were recorded and analyzed.

RESULTS:

Of the 77 patients enrolled, 70% had documented history of prior COVID-19 infection. 96% had comorbidities, the most common being diabetes. Majority received conventional amphotericin B deoxycholate formulation. 97% experienced at least one suspected ADR and the median ADR/patient was 3. Out of 214 ADRs, 91 were serious but there were no ADR-related deaths. The most common ADRs were hypokalemia (31.78%), infusion-related reactions (22.43%), and anemia (17.29%). Thirty-three patients had serum potassium <2.5 mEq/L, while 11 had serum magnesium <1.25 mg/dL. Doubling of pretreatment creatinine level was noted in 15 patients. Seventy percent ADRs were of “possible” category as per the World Health Organization Uppsala Monitoring Centre categorization.

CONCLUSION:

AmphoB deoxycholate use in mucormycosis patients was associated with a high incidence of electrolyte abnormalities and infusion-related reactions. All ADRs subsided with medical management and none were fatal. The safety data generated from this study may be useful in resource-limited settings where the far more expensive liposomal formulation is not being used.
Chimeric antigen receptor T cell
Authors: Singh Surjit , Khasbage Sameer , Kaur Rimple Jeet , Sidhu Jaspreet Kaur , Bhandari Bharti
Published: May 2024

During present decade, targeted drug therapy has been the epitome for treatment of cancer. Drugs like Imatinib, a tyrosine kinase receptor inhibitor and Trastuzumab, an human epidermal growth factor receptor-2/neu inhibitor, has been developed and accepted widely for management of chronic myeloid leukaemia and breast cancer respectively. Recent development among the various immunotherapies is adoptive cell transfer (ACT). Research on development of various types of ACT immunotherapy is going on, but so far, Chimeric antigen receptors T cell therapy (CAR-T) has achieved the maximum advancement in terms of clinical development. CARs are the modified receptors that integrates specificity and responsiveness onto immune cells to enhance the recognition of cancer cells. For the CAR-T, the T cells are sequestered from a blood of a participant via apheresis. DNA of particular antigen is injected into harvested T cells to generate CARs on cell surface. Following surface manifestation of receptors, multiplication is carried out in enriched media followed by infusion into patient. After infusion, CAR-T cells targeted and exterminate the cancer cells. Initially, only two drugs targeting CD19 as genetically modified autologous immunotherapy has been approved in CAR-T therapy i.e., Tisagenlecleucel and Axicabtagene Ciloleucel, which are discussed in detail in current review. Recently two more drugs got approval i.e., brexucabtagene ciloleucel and lisocabtagene maraleucel, both are directed against CD19, similar to tisagenlecleucel. CAR-T cell therapy is approved for management of Acute Lymphoblastic Leukaemia, Chronic Lymphocytic Leukaemia and lymphoma. CAR-T cell persistence responsible for effectiveness and safety concerns are barriers for their wide application among patients. Growth factor receptors and cluster of differentiation are new drugs targets that are being explored as effective immunotherapy against cancers.
Proteome architecture of human-induced pluripotent stem cell-derived three-dimensional organoids as a tool for early diagnosis of neuronal disorders
Authors: Negi R. , Srivastava A. , Srivastava A. K. , Pandeya Abhishek , Vatsa P. , Ansari U. A. , Pant A. B.
Published: May 2024

BACKGROUND AND OBJECTIVES:

Induced pluripotent stem cells (iPSCs) derived three-dimensional (3D) model for rare neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) is emerging as a novel alternative to human diseased tissue to explore the disease etiology and potential drug discovery. In the interest of the same, we have generated a TDP-43-mutated human iPSCs (hiPSCs) derived 3D organoid model of ALS disease. The high-resolution mass spectrometry (MS)-based proteomic approach is used to explore the differential mechanism under disease conditions and the suitability of a 3D model to study the disease.

MATERIALS AND METHODS:

The hiPSCs cell line was procured from a commercial source, grown, and characterized following standard protocols. The mutation in hiPSCs was accomplished using CRISPR/Cas-9 technology and predesigned gRNA. The two groups of organoids were produced by normal and mutated hiPSCs and subjected to the whole proteomic profiling by high-resolution MS in two biological replicates with three technical replicas of each.

RESULTS:

The proteomic analysis of normal and mutated organoids revealed the proteins associated with pathways of neurodegenerative disorders, proteasomes, autophagy, and hypoxia-inducible factor-1 signaling. Differential proteomic analysis revealed that the mutation in TDP-43 gene caused proteomic deregulation, which impaired protein quality mechanisms. Furthermore, this impairment may contribute to the generation of stress conditions that may ultimately lead to the development of ALS pathology.

CONCLUSION:

The developed 3D model represents the majority of candidate proteins and associated biological mechanisms altered in ALS disease. The study also offers novel protein targets that may uncloud the precise disease pathological mechanism and be considered for future diagnostic and therapeutic purposes for various neurodegenerative disorders.
Immunological factors associated with discordant virological response postcombination antiretroviral therapy in pediatric human immunodeficiency virus infection
Authors: Singh Ravinder , Maurya Shesh Prakash , Das Namrata , Kabra Sushil Kumar , Lodha Rakesh , Das Bimal Kumar
Published: May 2024

OBJECTIVES:

Evaluation of immunological factors responsible for discordant virological responses postcombination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-positive children aged <5 years.

MATERIALS AND METHODS:

Immunological profiling of enrolled 30 HIV-positive children was done at enrollment, 6 and 12 months. Flow cytometric analysis was performed for enumeration of counts and percentage of CD4+, CD8+, and CD19+ cells; expression of CD19, CD86, PD-1, CD3, CD8 and CD28 on lymphocytes was evaluated using whole blood staining technique with monoclonal antibodies. HIV-1 viral load was quantified using a real-time polymerase chain reaction. Serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin (IgM), and interleukin (IL)-7 were quantitated using quantitative enzyme-linked immunosorbent assay kits. The HIV-infected children were categorized into virological responders (VRs; HIV-1 plasma viral load <47 copies/mL) and virological nonresponders (VNRs; HIV-1 plasma viral load >1000 copies/mL) following 1-year cART.

RESULTS:

The frequency of CD28+ CTLs cells was higher (P < 0.0001), and the frequency of CD28-CTLs cells was lower (P < 0.0001) in VRs than VNRs. CD28+ and CD28-CTLs cells correlated with HIV-1 plasma viremia (r = −0.4695, P = 0.01; r = 0.40, P = 0.03, respectively). VRs had higher CD19 percentage (P = 0.04) and count (P = 0.01) than VNRs. CD19+ B cells in the VRs had lower expression of CD86 (P = 0.03) and PD-1 (P = 0.002) than VNRs. VR had lower levels of serum IgG (P = 0.03), IgM (P = 0.04), and IL-7 (P = 0.01) than VNRs.

CONCLUSIONS:

High baseline B-cell counts, lower serum IgG, IgM, IL-7 levels, lower activation and exhaustion of B cells, and higher frequency of CD28+ CTLs are associated with positive virological response, whereas elevated CD28-CTLs are associated with the poor virological outcomes in HIV-infected children.
Drug repurposing a compelling cancer strategy with bottomless opportunities
Authors: Dash Rasmita , Yadav Madhulika , Biswal Jyotirmaya , Samanta Shrabani , Sharma Tripti , Mohapatra Sujata
Published: May 2024

Drug discovery has customarily focused on a de novo design approach, which is extremely expensive and takes several years to evolve before reaching the market. Discovering novel therapeutic benefits for the current drugs could contribute to new treatment alternatives for individuals with complex medical demands that are safe, inexpensive, and timely. In this consequence, when pharmaceutically yield and oncology drug efficacy appear to have hit a stalemate, drug repurposing is a fascinating method for improving cancer treatment. This review gathered about how in silico drug repurposing offers the opportunity to quickly increase the anticancer drug arsenal and, more importantly, overcome some of the limits of existing cancer therapies against both old and new therapeutic targets in oncology. The ancient nononcology compounds' innovative potential targets and important signaling pathways in cancer therapy are also discussed. This review also includes many plant-derived chemical compounds that have shown potential anticancer properties in recent years. Here, we have also tried to bring the spotlight on the new mechanisms to support clinical research, which may become increasingly essential in the future; at the same time, the unsolved or failed clinical trial study should be reinvestigated further based on the techniques and information provided. These encouraging findings, combined together, will through new insight on repurposing more non-oncology drugs for the treatment of cancer.
Comparison of clinical effect of octreotide and pituitrin in treatment of upper gastrointestinal hemorrhage in cirrhosis
Authors: Zhu Yanli , Ren Yihua , Li Chunmei , Si Zhaoming , Chi Nannan
Published: May 2024

OBJECTIVE:

The objective of the study was to compare and observe the therapeutic effect of octreotide and pituitrin in upper gastrointestinal hemorrhage caused by cirrhosis.

MATERIALS AND METHODS:

In this prospective, randomized, open, single-blind, controlled, and single-center study, patients with upper gastrointestinal hemorrhage induced by cirrhosis were divided into control group (treated with pituitrin) and experimental group (treated with octreotide). The effective time, hemostasis time, and average bleeding volume of the two groups were observed and recorded, and the incidence of adverse reactions, rebleeding rate, and total effective rate of the two groups were compared.

RESULTS:

One hundred and thirty-two patients with upper gastrointestinal hemorrhage caused by cirrhosis were included from March 2017 to September 2018. By a single-blind method, the patients were randomly divided into control group (n = 66) and experimental group (n = 66). Compared with the control group, the effective time and hemostasis time of the drug were significantly shorter in the experimental group, whereas the average bleeding volume of patients was lower (average P < 0.05). Compare with the control group, the total effective rate was higher in the experimental group, whereas the incidence of adverse reactions was lower (average P < 0.05). During 1-year follow-up, early and late rebleeding rates and hemorrhage-related mortality between the two groups have no difference (average P > 0.05).

CONCLUSION:

In the treatment of upper gastrointestinal hemorrhage in cirrhosis, octreotide is superior to pituitrin, with advantages of quick onset, short hemostasis time, and less adverse reactions, which is helpful to control the rebleeding rate and bleeding-related mortality.
Deployment of iron uptake machineries as targets against drug resistant strains of mycobacterium tuberculosis
Authors: Gokhale Kunal Mohan , Iyer Aditya Manivannan
Published: May 2024

Mycobacterium tuberculosis (MTB) requires a perpetual supply of iron for its sustenance. Iron scarcity and its limited availability in the host environment because of an encounter of various sites during the establishment of infection has led to the evolution of strategies for iron uptake, which includes biosynthesis of iron-chelating molecules called siderophores, Heme uptake pathways, recently discovered host iron transport protein receptors like glyceraldehyde-3-phosphate dehydrogenase and the development of machinery for proper storage of the acquired iron and its regulation. The components of the iron uptake machineries are viable targets in multidrug-resistant tuberculosis, some of which include the MmpL3 heme transfer protein, MbtA enzyme, and the ESX-3 system, while employment of approaches like the synthesis of siderophore drug conjugates, heme analogs, xenosiderophores as drug delivery agents, and the blockade of siderophore recycling are encouraged too. Thus, the mentioned discoveries stand as promising targets against various strains of MTB.
Nephroprotective Potential of Syringic Acid in Experimental Diabetic Nephropathy
Authors: Sherkhane Bhoomika , Yerra Veera Ganesh , Sharma Anjana , Kumar Anil K , Chayanika Gundu , Kumar Arruri Vijay , Kumar Ashutosh
Published: May 2024

BACKGROUND:

Diabetic nephropathy (DN) is a chronic hyperglycemic manifestation of microvascular damage in the kidneys. Widespread research in this area suggests the involvement of perturbed redox homeostasis and autophagy in renal cells phrase- promote the progression of DN.

MATERIALS AND METHODS:

Reframed sentences-The present study investigates the pharmacological effect of Syringic acid (SYA), in streptozotocin (STZ, 55 mg/kg, i.p) induced diabetic nephropathy model and in high glucose (30 mM) challenged rat renal epithelial cells (NRK 52E) cells with a focus on oxidative stress and autophagy mechanisms.

RESULTS:

Both in vivo and in vitro experimental data revealed elevated oxidative stress markers along with compromised levels of nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal cellular redox-regulated transcription factor in renal cells upon glycemic stress. Elevated blood glucose also reduced the autophagy process as indicated by low expression of light chain (LC) 3-IIB in diabetic kidney and in NRK 52E cells subjected to excess glucose. SYA (25 and 50 mg/kg, p.o.) administration for 4 weeks to diabetic rats, Reframed sentence-preserved the renal function as evidenced by reduced serum creatinine levels as well as improved urine creatinine and urea levles as compared to non treated diabetic animals. At the molecular level, SYA improved renal expression of Nrf2 and autophagy-related proteins (Atg5, Atg3, and Atg7) in diabetic rats. Similarly, SYA (10 and 20 μM) co-treatment in high glucose-treated NRK 52E cells displayed increased levels of Nrf2 and autophagy induction.

CONCLUSION:

Results from this study signify the renoprotective effect of SYA and highlight the modulation of oxidative stress and autophagy mechanisms to mitigate diabetic kidney disease.
Variation in normative values of major clinical biochemistry analytes in healthy reproductive-age women in India
Authors: Ganie Mohd Ashraf , Chowdhury Subhankar , Suri Vanita , Joshi Beena Nitin , Bhattacharya Prasanta Kumar , Agarwal Sarita , Malhotra Neena , Sahay Rakesh , Jabbar P. K. , Rozati Roya , Shukla Amlin , Rashid Haroon , Bashir Rohina , Wani Imtiyaz , Nair Abhilash , Arora Taruna Katyal , Kulkarni Bharati
Published: May 2024

OBJECTIVES:

Clinical biochemistry reference intervals (RIs) play a crucial role in interpreting patient test results and making informed clinical decisions. Using data from an ongoing Indian Council of Medical Research-National task force study on healthy women, normative ranges for commonly analyzed biochemical analytes were established.

MATERIALS AND METHODS:

A total of 13,181 women of reproductive age (18–40 years) were recruited from different urban and rural regions of the country, of which 9898 women signed an informed consent were included. Among these, women having features of hyperandrogenism, menstrual cycle irregularities, and comorbidities were excluded. RIs of 22 analytes were computed in the remaining 938 women controls. To estimate the 95% range of the reference distribution, the limits of the 2.5th percentile and the 97.5th percentile were used in the study.

RESULTS:

Mean ± standard deviation of age and body mass index of participants was 30.12 ± 6.32 years and 22.8 ± 3.36 kg/m2 respectively. Centiles (2.5th–97.5th) of liver function parameters, lipid parameters, glycaemic parameters, and renal parameters are presented. No significant difference in analytes was observed in relation to the area of residence, and age groups except in albumin (P = 0.03). The distribution of most of the parameters was consistent with the various RI studies conducted in India as well as other countries.

CONCLUSION:

This is the first study generating biochemical RIs data among a large representative sample of healthy reproductive-age women recruited using a robust design across the country. The resource may serve as a reference range for common biochemical analytes for future in this age group.
In search for a panacea for coronavirus disease-19
Authors: Maheshwari Nidhi , Roy Vandana
Published: May 2024

OBJECTIVE:

To analyze the clinical trials that are registered on the Clinical Trial Registry of India (CTRI) portal for a year, for the treatment, prevention, and supportive therapy of coronavirus disease-19 (COVID-19).

MATERIALS AND METHODS:

All the trials registered on CTRI (since January 2020 till January 2021) for therapeutic, preventive, and supportive interventions for COVID-19 were searched with the keywords “Coronavirus,” “COVID-19,” “SARS-COV-2,” and “2019-nCoV”. These registered studies were analyzed as follows: Trials under different systems of Medicine-Allopathy/Homeopathy/Ayurveda/Unani/Yoga/Naturopathy. The Allopathy trials were further analyzed in detail: Intervention, design, comparator, number of subjects, duration, and approvals taken.

RESULTS:

A total of 1597 records were found. After excluding the overlaps, behavioral and other studies conducted to understand the diagnosis, epidemiology, a total of 419 registered studies were included for further analysis. Out of these 419 studies, 166 (39.6%) were in Ayurveda, 154 (36.7%) in Allopathy, 33 (7.8%) in Homeopathy, 30 (7%) in Unani/Siddha, 18 (4.3%) in Yoga and Naturopathy and 18 (4.3%) in Nutraceuticals. A total of 264 interventions had been registered in 419 clinical trials. Sixty-seven interventions were being studied under allopathy in 154 studies. Same product was being evaluated in differently designed protocols with different endpoints. Maximum number of trials and subjects were for Hydroxychloroquine 25 (17,998), Ivermectin 11 (2820), Convalescent Plasma 11 (3982), Remdesivir 8 (3725), Tocilizumab 6 (884), and Azithromycin 6 (582).

CONCLUSIONS:

In response to the COVID-19 pandemic, Indian researchers came forward from all the systems of medicine to evaluate interventions for prophylaxis or treatment of the disease. The involvement of AYUSH systems of medicine was specifically more in this regard. A wide variation and heterogeneity in doses and outcomes were observed in trial designs which might make it difficult to generalize the study results when they are made available. Urgent analyses of studies involving interventions on the treatment advisory of the Government may help the healthcare providers take more informed decisions for managing COVID-19 patients in India.
Prevalence of CYP2C9 and CYP2C19 variants and the impact on clopidogrel efficacy in patients having CYPC19*2 variant
Authors: Mehta Meha P. , Gajjar Normi D. , Patel Rutvi J. , Joshi Lipi P. , Shah Gaurang B.
Published: May 2024

OBJECTIVE:

Human cytochrome p450 enzymes play an important role in the metabolism of various substances. The CYP2C subfamily consists of various important drug-metabolizing enzymes such as CYP2C9 and CYP2C19. The objectives of the study include the determination of the frequency of genetic variants (CYP2C9*2, CYP2C9*3, and CYP2C19*2) of selected enzymes using allele-specific polymerase chain reaction (ASPCR) and its comparison with Indian as well as global past frequencies. We also aimed to study the impact of genetic mutation on clopidogrel efficacy and compare the efficacies between patients with and without CYP2C19*2 genetic variant.

METHODOLOGY:

In this study, the prevalence of variants CYP2C19*2, CYP2C9*2, and CYP2C9*3, the most popular variants of the respective enzymes, was determined using the ASPCR method. The correlation between the CYP2C19*2 variant and the antiplatelet activity of clopidogrel was studied using platelet aggregation assay (PAA).

RESULTS:

The determined frequencies of CYP2C19*2, CYP2C9*2, and CYP2C9*3 are 46%, 9%, and 12%. These frequencies are indicative of homozygous as well as heterozygous mutations. Reduced clopidogrel efficacy was observed in patients with a heterozygous mutation of CYP2C19*2 variant.

CONCLUSIONS:

The observed frequencies are not significantly different from that observed in earlier reported studies conducted across India and the world. Antiplatelet activity, as measured using the PAA method, was significantly lesser in patients having the CYP2C19*2 variant. The therapy failure in these patients can lead to serious cardiovascular consequences, and we propose determining the presence of the CYP2C19*2 variant before initiation of clopidogrel therapy.
A clinical study on the pattern of antimicrobial drug use and drug resistance in patients with ventilator-associated pneumonia in a tertiary care hospital
Authors: Rezia Abisha , Vijendra R.
Published: May 2024

CONTEXT:

Ventilator-associated pneumonia (VAP) develops nearly in about one-third of the patients, 48 h after receiving mechanical ventilation. Common pathogens are Pseudomonas aeruginosa,
Staphylococcus aureus, Acinetobacter spp., Klebsiella spp., Escherichia coli,
Proteus spp., Enterobacter spp. and Enterococcus spp. including multidrug-resistant pathogens.

AIM:

The study aims to assess the pattern of antimicrobial drug use in VAP and to assess the etiological organisms and their drug sensitivity and resistance pattern.

SETTINGS AND DESIGN:

Study participants admitted to Kempegowda Institute of Medical Sciences Hospital and Research Centre, Bengaluru, and who developed VAP were included in this prospective observational study.

SUBJECTS AND METHODS:

Bronchial secretions were subjected to microbiological analysis. The etiological organisms, their drug sensitivity and resistance pattern, and the outcome of drug therapy were recorded. The clinical course of the study participants was monitored till either the resolution of pneumonia or the demise of the participant.

STATISTICAL ANALYSIS USED:

Qualitative data were analyzed using the Chi-square test or Fischer's exact test and quantitative data using the independent t-test.

RESULTS:

Early VAP was seen in 91.7% and late VAP in 8.3% of the participants. The organisms isolated were S. aureus, Enterococcus spp., Acinetobacter spp., Klebsiella pneumoniae and P. aeruginosa. Majority of the study participants with early VAP (75%, n = 41) completely recovered from pneumonia and 80%, n = 4 participants with late VAP recovered completely.

CONCLUSION:

The organisms had a varied sensitivity and resistance pattern. The clinical outcome was multifactorial and its association with specific antimicrobial agents cannot be drawn.
Drug resistance profile in postbiliary and gastrointestinal surgical-site infection cases from a tertiary care hospital
Authors: Kalita Deepjyoti , Rajbangshi Madhab Chandra , Deka Sumi , Sarma Ridip Kumar , Deka Sangeeta
Published: May 2024

In the developing world, surgical-site infection (SSI)-associated pathogens are becoming more drug resistant implicating higher morbidity and management cost. Here, we tried to analyze the drug resistance pattern in our SSI-related isolates. Over 2 years, 191 clinically diagnosed SSIs (postbiliary tract and postgastrointestinal surgery) were included, and wound swabs were processed by conventional aerobic and anaerobic culture. Antibiotic minimum inhibitory concentration (MIC) was determined by the Epsilometer testing. Multidrug-resistant phenotypes were detected as per guidelines. The rate of SSI was 5.3% with Klebsiella, Staphylococcus, and Pseudomonas, growing predominantly, and no anaerobe detectable. About 19.4% of Staphylococcus aureus were methicillin-resistant S. aureus, and one-third of them had raised macrolide MIC. About 58.2% of Enterobacteriaceae isolates were extended-spectrum beta-lactamase producers. Isolates with raised meropenem MIC were observed. Antibiotic-resistant level in SSI cases is alarmingly high, and in susceptible strains, MIC is approaching the resistant level. Urgent corrective action is an emergency necessity.
Materiovigilance Programme of India
Authors: Saifuddin P. K. , Tandon Moksh , Kalaiselvan Vivekanandan , Suroy Benjamin , Pattanshetti Vidya , Prakash Ajay , Medhi Bikash
Published: May 2024

Postmarketing vigilance system for medical devices in India is not as vigorous as of drugs. W Materiovigilance involves post marketing surveillance of adverse events caused by medical devices. As per directive of WHO, many countries including India have established their own post marketing surveillance system. In India it is known as Materiovigilance Programme of India (MvPI). This article reviews the current state of MvPI, compares it with developed countries, identifies gaps, and recommends specific measure to strengthen the existing program.