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This review article delves into the details of the 3R-Refinement principles as a vital framework for ethically sound rodent research laboratory. It highlights the core objective of the refinement protocol, namely, to enhance the well-being of laboratory animals while simultaneously improving the scientific validity of research outcomes.Through an exploration of key components of the refinement principles, the article outlines how these ethics should be implemented at various stages of animal experiments. It emphasizes the significance of enriched housing environments that reduce stress and encourage natural behaviors, non-restraint methods in handling and training, refined dosing and sampling techniques that prioritize animal comfort, the critical role of optimal pain management and the importance of regular animal welfare assessment in maintaining the rodents well-being. Additionally, the advantages of collaboration with animal care and ethics committees are also mentioned. The other half of the article explains the extensive benefits of the 3R-Refinement protocol such as heightened animal welfare, enhanced research quality, reduced variability, and positive feedback from researchers and animal care staff. Furthermore, it addresses avenues for promoting the adoption of the protocol, such as disseminating best practices, conducting training programs, and engaging with regulatory bodies. Overall, this article highlights the significance of 3R-Refinement protocol in aligning scientific advancement with ethical considerations along with shaping a more compassionate and responsible future for animal research.
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Background: Knowledge of pediatric COVID-19 is important to determine those at risk for severe disease and mortality. There is limited data on risk factors for development of severe disease and predictors of mortality amongst children with COVID-19, especially from the developing nations. We aimed to study the profile, risk factors for severe COVID-19 and predictors of mortality in children with laboratory confirmed COVID-19.Methods: This prospective observational study was conducted from April to September 2020 in the Department of Pediatrics of a referral COVID-care hospital in Northern-India. All children 1 month to 18 years of age, hospitalized in the Pediatrics Department and having a positive Reverse Transcriptase-Polymerase chain reaction (RT-PCR) for SARS-CoV-2 infection on their combined oro-nasopharyngeal swab were enrolled.Results: A total of 335 SARS-CoV-2 positive children were enrolled with median age of 6 years, slight male predominance (54%) and 24.4% infants. Commonest presentations were respiratory (47.7%), gastrointestinal (33.3%) and neurological (14.9%) with moderate/severe disease in 24%, mortality in 4.8%, co-morbidities in 20.5% and co-infections in 17.9%. Risk factors for severe disease were underlying co-infection (p=0.017), associated tuberculosis (p=0.0015), associated culture positive bacterial sepsis (p=<0.001) and being underweight (p<0.001). Overweight/obese children had less severe COVID-19 (p=0.0016). Predictors of mortality were co-infections (p=0.0019), hypoxia (p<0.001), neurological manifestations (p=0.016), acute respiratory distress syndrome (p<0.001), acute kidney injury (p=0.05), shock (p<0.001), thrombocytopenia (p=0.021), leucopenia (p=0.028), lymphopenia (p=0.021), high Neutrophil:Lymphocyte ratio (p=0.02), coagulopathy (p=0.02), azotemia (p=0.038) and raised creatinine (p=0.05).Conclusions: Children with identified risk factors for severe disease and mortality should receive prioritized treatment.
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Objective: To assess the emerging trend of Non-operative Management and image guided interventions over surgery in a tertiary care hospital in a developing nation. Data regarding patients who underwe Methods: nt Non-Operative Interventions (NOI) or Non-Operative Management (NOM) in VMMC and Safdarjung hospital, New Delhi, India over past 3 years was collected retrospectively from hospital database. Max diameter of liver abscess mana Results: ged nonoperatively ranged from 3.5 to 14 cm. Mean diameter was 7.15 +/- 3.20 cm. Mean volume of the abscess was 538 ml. 43.33% of the abscesses were ruptured. 73.33% of the patients underwent pigtail insertion and the rest underwent ultrasound guided aspiration. 12 patients underwent PTBD in the center over past 3 years. All the patients had malignant etiology of some sort. 75% patients had carcinoma of Gall bladder, and the rest had biliary stricture of malignant nature. Conclusion: NOIs have revolutionized management of several entities for which surgery was sole resort until few decades back. However, these facilities come with their own set of limitations. There is a paucity in literature in the developing world regarding outcome of NOI
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Purpose: To analyze the presence of severe acute respiratory syndrome coronavirus 2 (SARS?CoV?2) in tears/conjunctival epithelium and assess the cytomorphological changes in the conjunctival epithelium of coronavirus disease 2019 (COVID?19) patients. Methods: In this pilot study, patients with moderate to severe COVID?19 were recruited from the COVID ward/intensive care unit of the institute. Tears and conjunctival swabs were collected from COVID?19 patients and sent to the virology laboratory for reverse transcription polymerase chain reaction (RT?PCR) testing. Conjunctival swabs were used to prepare smears, which underwent cytological evaluation and immunocytochemistry for SARS?CoV?2 nucleocapsid protein. Results: Forty?two patients were included. The mean age of participants was 48.61 (range: 5–75) years. Seven (16.6%) patients tested positive for SARS?CoV?2 ribonucleic acid in tears samples, four (9.5%) of which were positive on conjunctival swab by RT?PCR in the first test. Cytomorphological changes were observed significantly more in smears from patients with positive RT?PCR on tear samples, including bi?/multi?nucleation (p = 0.01), chromatin clearing (p = 0.02), and intra?nuclear inclusions (p < 0.001). One case (3.2%) showed immunopositivity for SARS?CoV?2; this patient had severe disease and the lowest Ct values for tear and conjunctival samples among all positive cases. Conclusion: Conjunctival smears from patients with COVID?19 revealed cytomorphological alterations, even in the absence of clinically significant ocular infection. However, viral proteins were demonstrated within epithelial cells only rarely, suggesting that although the conjunctival epithelium may serve as a portal for entry, viral replication is possibly rare or short?lived.
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The United States Food and Drug Administration (FDA) approved betibeglogene autotemcel (beti-cel), the first cell-based gene therapy for adult and pediatric patients with ?-thalassemia in August, 2022. This update details this and other novel therapies that have emerged in the treatment of ?-thalassemia, apart from transfusion and iron chelation, with particular focus on newly approved gene therapy
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Cardiovascular disease (CVD) related mortality and morbidity heavily strain society. The relationship between external risk factors and our genetics have not been well established.It is widely acknowledged that environmental influence and individual behaviours play a significant role in CVD vulnerability, leading to the development of polygenic risk scores (PRS). We employed the PRISMA search method to locate pertinent research and literature to extensively review artificial intelligence (AI)-based PRS models for CVD risk prediction.Furthermore, we analyzed and compared conventional vs. AI-based solutions for PRS. We summarized the recent advances in our understanding of the use of AI-based PRS for risk prediction of CVD. Our study proposes three hypotheses: i) Multiple genetic variations and risk factors can be incorporated into AI-based PRS to improve the accuracy of CVD risk predicting. ii) AI-based PRS for CVD circumvents the drawbacks of conventional PRS calculators by incorporating a larger variety of genetic and non-genetic components, allowing for more precise and individualised risk estimations. iii) Using AI approaches, it is possible to significantly reduce the dimensionality of huge genomic datasets, resulting in more accurate and effective disease risk prediction models. Our study highlighted that the AI-PRS model outperformed traditional PRS calculators in predicting CVD risk. Furthermore, using AI-based methods to calculate PRS may increase the precision of risk predictions for CVD and have significant ramifications for individualized prevention and treatment plans.
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Objective@#Internet gaming disorder (IGD) is an increasingly common behavioral addiction, with an estimated global prevalence of 3%. A variety of pharmacological treatments have been used to treat IGD, yet no review to date has synthesized clinical trials evaluating their efficacy. This systematic review therefore synthesized the literature reporting on clinical trials of pharmacological treatments for IGD. @*Methods@#We reviewed articles from MEDLINE, Embase, PubMed Central, CINAHL, and PsycINFO that were published as of March of 2022. A total of 828 articles were retrieved for review and 12 articles were included, reporting on a total of 724 participants. @*Results@#Most participants were male (98.6%), and all were currently living in South Korea. The most common drugs used to treat IGD were bupropion, methylphenidate, and a range of selective serotonin reuptake inhibitors. The Young Internet Addiction Scale was the most frequently used to measure gaming-related outcomes. All studies reported reduced symptoms of IGD from pre- to post-treatment. Across all clinical trials, IGD symptom reductions following the administration of pharmacological treatments ranged from 15.4% to 51.4%. A risk of bias assessment indicated that only four studies had a low risk of bias. @*Conclusion@#Preliminary results suggest that a wide array of pharmacological interventions may be efficacious in the treatment of IGD. Future studies using double-blind randomized controlled trial designs, recruiting larger and more representative samples, and controlling for psychiatric comorbidities are needed to better inform understanding of pharmacological treatments for IGD.
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Background & objectives: The overall adult prevalence of HIV in India was estimated to be 0.22 per cent in 2019. The HIV prevalence among men who have sex with men (MSM), a high-risk group for HIV, was estimated to be 4.3 per cent, which is 16 times higher than the national average. In Delhi, the estimated prevalence among MSM was 1.8 per cent. Despite free HIV testing services being made available by the National AIDS Control Programme for more than two decades, many MSM were not aware about their HIV status. Therefore, newer testing strategies are needed. Oral HIV self-testing (HIVST) has proved to be one such promising innovation. At present, there are no programme guidelines on HIVST and oral HIVST kit is not available in India. The aim of this study was to understand the perceived advantages and disadvantages of introduction of oral HIVST strategy among MSM. Methods: MSM who were registered with the selected non-governmental organizations working as targeted intervention sites in Delhi, India, were recruited for focus group discussions (FGDs) between January and May 2021. For the purpose of this study, MSM were defined as males who had anal/oral sex with male/hijra partner in the past one month. A total of six FGDs were conducted using a prepared FGD guide. The FGD guide included questions on problems faced during conventional HIV testing, participants’ awareness, acceptability and perceptions of oral HIVST. The data were manually coded and entered in NVivo release 1.5 and themes were identified. Results: A total of 67 respondents participated in the FGDs. A total of 28.4 per cent MSM were beggars at traffic lights, 12 per cent were sex workers and 11.9 per cent were bar/event dancers. Nearly half (50.7%) of the participants had undergone HIV testing less than twice in the preceding one year. None of the MSM were aware about oral HIVST. Perceived advantages of oral HIVST were ease of use, confidentiality and the non-invasive pain-free procedure. Perceived concerns included lack of post-test counselling, linkage to care, poor mental health outcomes and forced testing. Interpretation & conclusions: Most MSM had positive perceptions about oral HIVST. Therefore, it is likely that the introduction of oral HIVST may result in higher uptake of HIV testing among MSM
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Objective: To evaluate and compare the effect of variation in storage temperatures and duration on a tensile load at failure of elastomeric modules. Methods: In total, 140 modules were used in the study, 20 of which were tested on day 0 as received from a company using a Universal testing machine for baseline estimation of tensile load at failure. The rest 120 modules were divided into 6 groups. Groups I, II, and III modules were stored at low (T1 = 1–5°C), moderate (T2 = 20–25°C) and high (T3 = 35–40°C) temperatures, respectively, for 6 months. Groups IV, V and VI modules were stored at temperatures T1, T2 and T3 for 1 year, respectively, and were tested for tensile load at failure. Results: The tensile load at failure for the control group was 21.588 ± 1.082 N and for 6?month interval at temperatures T1, T2 and T3 was 18.818 N ± 1.121 N, 17.841 N ± 1.334 N and 17.149 N ± 1.074 N, respectively, and for 1 year, it was 17.205 N ± 1.043 N, 16.836 N ± 0.487 N and 14.788 N ± 0.781 N, respectively. The tensile load at failure decreased significantly from 6 months to 1 year among each temperature group. Conclusions: Maximum force degradation was seen in modules at high temperature followed by medium temperature and low temperature at both 6 months and 1 year intervals, and tensile load at failure decreased significantly from 6 months to 1 year storage duration. These results conclude that the temperature and duration at which the samples were exposed during storage produce a significant change in the forces exerted by the modules.
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SARS-CoV-2, the virus that causes the COVID-19 infection, has been linked to all sorts of long-term health issues.Diabetes mellitus has a bidirectional relationship with COVID-19. Poorly controlled diabetes increases the severity of COVID-19 and is associated with increased morbidity and mortality. COVID-19 pandemic has also resulted in poor control of diabetes, progression of prediabetes to diabetes, increase in number of new onset diabetes.
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Introduction: Fragility hip fractures in nonagenarian patients pose a great challenge in management. To the best of our knowledge, no study has previously evaluated the outcomes and risk factors for mortality after hip fractures in this subgroup of population from the Indian subcontinent. Materials and Methods: A retrospective observational study was performed on nonagenarian patients (aged ?90) who underwent surgery for hip fractures between March 2016 and March 2019. The patients were divided into two groups: “survivor group” (Group A) and “mortality group” (Group B). The demographic data, type of fracture, side of fractured limb, preinjury ambulatory status, American Society of Anesthesiologists (ASA) status, comorbidities, time interval from injury to surgery, operative time, length of hospital stay, and postoperative ambulatory status were recorded from hospital medical records and were studied between the two groups. The follow-up duration of the study was 1 year. Results: Thirty-four patients were included in the study. Both the groups had 17 patients each. Cardiac dysfunction was the most common cause of mortality. The time interval from injury to surgery (odds ratio [OR] = 11.2), gender (OR = 0.23) and postoperative mobility status (OR = 0.07) were found to be significantly different between the two groups. No significant difference in ASA grade, comorbidities, fracture type, preinjury ambulatory status, operative time, and length of hospital stay was seen between the two groups. Conclusions: Risk factors for mortality after hip fracture surgery in the nonagenarian population are male gender, delay in surgery (>3 days) and poor ambulatory status in the postoperative period. Hence, the aim for such patients with hip fractures should be to perform an early surgery and encourage an early ambulation.
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Background & objectives: Accurate and early diagnosis is imperial in the management of endometriosis, endometrioid carcinoma of ovary (ECO) and endometrioid endometrial cancer (EC), yet there are no definitive diagnostic methods available for these diseases. Therefore, the present study was aimed to evaluate the diagnostic potential of differentially expressed miRNAs in serum samples of women with endometriosis, ECO and EC to establish them as diagnostic biomarkers. Methods: Blood samples (5 ml) were obtained from 40 patients (n=10/study group) undergoing laparoscopy/laparotomy/hysterectomy. miRNA-rich RNA was extracted from the serum samples, and quantitative real-time (qRT)-PCR was performed to check the expression levels of miR-16, miR-99b, miR-20a, miR-145, miR-143 and miR-125a in all the samples. Receiver operating characteristic (ROC) curve analysis was done to check the diagnostic potential. Results: In endometriosis, miR-16 was downregulated (P<0.05) whereas miR-99b, miR-125a, miR-143 and miR-145 were upregulated (P<0.05). In ECO group, downregulated expression of miR-16 and miR-125a (P<0.05) was observed, whereas miR-99b, miR-143 and miR-145 were upregulated (P<0.05). In endometrioid EC, miR-16, miR-99b, miR-125 and miR-145 were downregulated (P<0.05), whereas miR-143 was upregulated (P<0.05). ROC curve analysis showed that, for endometriosis, miR-99b, miR-125a, miR-143 and miR-145 served as diagnostic markers. miR-145 showed diagnostic power for ECO, and for endometrioid EC, miR-16, miR-99b, miR-125a and miR-145 showed diagnostic potential. Interpretation & conclusions: The present findings suggested that certain circulating miRNAs (miB99b, miR-16, miR-125a, miR-145) might act as indicators and discriminators of endometriosis and endometrioid subtypes of EC and ovarian cancer and might serve as potential biomarkers for early diagnosis and management of these debilitating diseases.
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Purpose@#The purpose of this study was to assess the microbiota in middle cerebral artery thrombi retrieved in mechanical thrombectomy arising out of symptomatic carotid plaque within 6 hours of acute ischemic stroke. Thrombi were subjected to next-generation sequencing for a bacterial signature to determine their role in atherosclerosis. @*Materials and Methods@#We included 4 human middle cerebral artery thrombus samples (all patients were male). The median age for the patients was 51±13.6 years. Patients enrolled in the study from Pacific Medical University and Hospital underwent mechanical thrombectomy in the stroke window period. All patients underwent brain magnetic resonance angiography (MRA) and circle of Willis and neck vessel MRA along with the standard stroke workup to establish stroke etiology. Only patients with symptomatic carotid stenosis and tandem lesions with ipsilateral middle cerebral artery occlusion were included in the study. Thrombus samples were collected, stored at –80 degrees, and subjected to metagenomics analysis. @*Results@#Of the 4 patients undergoing thrombectomy for diagnosis with ischemic stroke, all thrombi recovered for bacterial DNA in qPCR were positive. More than 27 bacteria were present in the 4 thrombus samples. The majority of bacteria were Lactobacillus, Stenotrophomonas, Pseudomonas, Staphylococcus, and Finegoldia. @*Conclusion@#Genesis of symptomatic atherosclerotic carotid plaque leading to thromboembolism could be either due to direct mechanisms like acidification and local inflammation of plaque milieu with lactobacillus, biofilm dispersion leading to inflammation like with pseudomonas fluorescence, or enterococci or indirect mechanisms like Toll 2 like signaling by gut microbiota.
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Myeloid sarcoma (MS) is a rare extramedullary neoplasm of myeloid cells, which can arise before, concurrently with, or following hematolymphoid malignancies. We report 04 such cases of MS, diagnosed in this institute over a period of 6 years, during various phases of their respective myeloid neoplasms/leukemias. These cases include MS occurring as a relapse of AML (Case 1), MS occurring as an initial presentation of CML (Case 2), MS occurring during ongoing chemotherapy in APML (Case 3), and MS presenting as a progression of MDS to AML (Case 4). In the absence of relevant clinical history and unemployment of appropriate immunohistochemical (IHC) studies, these cases have a high risk of being frequently misdiagnosed either as Non-Hodgkin's Lymphoma (NHL) or small round cell tumors or undifferentiated carcinomas, which may further delay their management, making an already bad prognosis worse. This case series has been designed to throw light on the varied presentation of MS and the lineage differentiation of its neoplastic cells through the application of relevant IHC markers along with their clinical correlation.
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Humanos , Masculino , Femenino , Preescolar , Adolescente , Persona de Mediana Edad , Anciano , Sarcoma Mieloide/patología , Síndromes Mielodisplásicos/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mieloide Aguda/patología , Leucemia Promielocítica Aguda/patología , Errores Diagnósticos/prevención & controlRESUMEN
Background: Diagnostic accuracy of intra-operative frozen section (FS) depends largely on quality of tissue sections backed by good clinical communication and experience of reporting pathologist. Periodic audit of this consultation in surgical pathology help in assessing the efficiency of procedure and addressing the pitfalls. In this study authors have analysed the spectrum, indications and assessed the accuracy of FS consultation in their institution.Methods: A retrospective study of 212 consequent tissue specimens submitted for FS over two years in study centre was conducted. The FS and corresponding formalin fixed paraffin embedded (FFPE) tissue section with their final histopathological examination (HPE) reports were studied and analyzed. The results were classified in concordant, discordant and deferred categories. Accuracy rates and discordant frequencies were calculated and comparison with other similar studies was done. Reasons for inaccuracies were deduced.Results: A total of 212 tissue specimens for FS were reported over two years in this study institute, six of which showed discordant results. Most common site of FS in this study centre was from central nervous system (CNS) lesions (28.77%). Indications for intra-operative consultation were mainly for establishment of tumor diagnosis (66.51%) and status of margins (29.25%). The accuracy rate was found to be 97.17% with error rate of 2.83%. On analysis of discordant cases; the reason for inaccuracy was mainly due to interpretation error (83.33%).Conclusions: The audit of FS consultation established that accuracy rates of this study institution are comparable with most international quality control statistics for FS. The discordant cases were mostly false positive hence emphasising that a variable degree of reservation is required while interpreting and communicating the FS results. The closest possible diagnosis should be communicated on FS and definitive diagnosis should be deferred to HPE in case of doubt.
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Diagnosis and treatment planning in skeletal discrepancy and disorders requires radiographic assessment. Disturbance in growth and development alters the morphologic build-up of bony structures, which makes evaluation difficult. Out of these skeletal landmarks Point ANS is seen affected in many conditions like cleft lip and palate, Binders Syndrome, Down’s Syndrome, nasomaxillary hypoplasia, etc., wherein maxilla is mostly affected. Surgical intervention if required needs exact evaluation of point ANS. The purpose of the present study is thus to revisit Point ANS to aid in the cephalometric evaluation in cases where location of Point ANS is difficult; thus, making treatment planning easy. METHODS50 lateral cephalograms were evaluated by taking reference of skeletal landmarks and linear measurements were done. RESULTSLinear measurements from Point Ptm’-Ba’, Ba’-ANS’, ANS’-A were found to be proportionally equal with a ratio of 1:1:1. CONCLUSIONSLinear distance of Point ANS to N perpendicular (ANS’) line was approximately half of the linear distance of Point Ba’-A, while Point ANS is placed approximately 5±2 mm ahead of the line N perpendicular.
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Background: Cataract is considered as one of the most common causes of visual impairment and the leading cause of blindness in the world. Age related cataract occurs in people above 50 years of age and the its pathogenesis is multifactorial. Therefore, the present study was aimed to assess the prevalence and risk factors for cataract.Methods: Community based cross sectional study was conducted among adults residing at urban areas of South Bihar. The data was collected by interview method, using pre-tested semi-structured questionnaire which contains socio-demographic data, dietary habits, history of diabetes or hypertension, family history of cataract and long-term sun exposure.Results: Among 240 participants, 94 (39.2%) were male and 146 (60.8%) were female. Maximum participants were aged more than 70 years. The prevalence of cataract was 52.1%.Conclusions: The prevalence of cataract was quite high and was significantly associated with age, long term sun exposure and family history of cataract.
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The present study was carried out using first lactation monthly test-day milk yield records of 466 crossbred (HF × Sahiwal) cattle calved from 2000 to 2018 sired by 89 bulls maintained at Directorate of Livestock Farms, GADVASU, Ludhiana. Mixed model analysis was carried out by least-squares maximum likelihood programme to study the effects of non-genetic factors on first full lactation milk yield (FFLMY), first lactation 305-day milk yield (FL305MY) and monthly test-day (TD) milk yield records of crossbred cattle. The least squares means of different monthly TD milk yields (1st to 11th) were 12.05 ± 0.42, 15.65 ± 0.42, 15.38 ± 0.44, 14.44 ± 0.43, 13.79 ± 0.41, 12.88 ± 0.40, 12.27 ± 0.42, 11.83 ± 0.37, 10.85 ± 0.42, 10.64 ± 0.45 and 10.28 ± 0.50 kg, respectively. For FFLMY and FL305MY the means were 4979.60±184.45 and 3818.17±103.26 kg. The effects of different AFC groups were non-significant on TDs and FL305MYs, whereas it was significant (p≤0.01) for FFLMY. The season was significant (p≤0.01) for all the monthly TDs whereas it was non-significant for FFLMY and FL305MY. The sire was significant (p≤0.01) for most of the TDs and FL305MYs except the later TDs (9th, 10th and 11th TD) and FFLMYs. The present investigation revealed the importance of non-genetic factors in performance evaluation of crossbred cattle based on monthly test-day milk yield, FL305MY and FFLMY records