Truth in a pill

In 1937, the elixir sulphanilamide disaster was one of the mass poisonings. It occurs due to the presence of the diluent diethylene glycol in the elixir preparation of sulphanilamide. Because of its therapeutic use, around 100 patients died. In response to the calamity, Federal Food, Drug and Cosmetic Act was passed in the year 1938 by U.S congress and this ensured the proof of safety before the drug comes to market. The similar incident occurred for thalidomide in late 1950s and early 1960s when the drug was used for the treatment of nausea in pregnant women and resulted in children with birth defects. The development of drugs is a complex and costly process and it takes around 10-15 years for the drug to develop. Because of these reasons, the development of generic drugs is essential and this review will deal about the use of generic drugs and also its advantages with limitations.

Diagnostic accuracy of frozen section: an institutional observational study

Background: Frozen section is an important tool in rapid intra-operative diagnosis. It is commonly used during surgical procedures to detect malignancy so that modifications of surgery can be decided at the time of surgery on the table. Frozen section is also performed for evaluation of surgical margins and detection of lymph node metastasis. In addition, it is applied for detection of unknown pathological processes. The objective of this study was to assess the accuracy of frozen section diagnosis in comparison to gold standard histopathological diagnosis and to find concordance and discordance rate of frozen section with histopathological report. Aim of the study was comparison between frozen section and routine formalin fixed paraffin sections in various tissues. Methods: This is a retrospective cross-sectional study of 272 frozen section samples done in the department of pathology in Bharati Medical College and Research Centre, Dhankawdi- Pune and Excel diagnostics Pune, in Maharashtra from January 2022 to April 2023. The study included all frozen section samples with their permanent tissue samples received for final histopathological evaluation. Results: Out of 272 cases, 268 had concordant diagnosis on frozen section and permanent paraffin embedded section. Out of 4 discordant cases, 3 showed false negative result and definite diagnosis of one case could not be given on frozen section. The overall diagnostic accuracy of frozen section was 98.52%. Conclusions: Frozen section is a reliable intra operative diagnostic tool. Intra-operative diagnosis helps surgeon to take important intra-operative decision to avoid second surgery. Accuracy of frozen section can be improved by avoiding sampling errors and experience of the histopathologist.

Assessment of Genetic Variability for Morpho-physiological and Yield Traits in Bread Wheat (Triticum aestivum L.)

In order to estimate genetic variability parameters for seventeen traits of wheat, 28 F1s were obtained by crossing 8 parents in 8×8 diallel fashion, excluding reciprocals and evaluation trial was laid down in randomised complete block design at Pantnagar, Uttarakhand. Analysis of variance revealed that highly significant differences between genotypes exist for all seventeen characters. Eleven out of seventeen characters were observed to exhibit elevated values for both the PCV and GCV. The observed phenotypic coefficient of variation (PCV) values was determined to be greater than the genotypic coefficient of variation (GCV) values, indicating that the expression of traits is comparatively less influenced by environmental factors. A significant degree of heritability, along with a notable genetic advance, was observed for various traits, including flag leaf area, followed by grain yield, biological yield, canopy temperature depression (CTD), harvest index, tillers per plant, peduncle length, grains per spike, awn length, plant height, grain filling duration, spikelet per spike, spike length, and normalised difference vegetation index (NDVI) content. This study has thus identified significant genetic variability in wheat traits, highlighted traits with high heritability and genetic advance, and suggested that these traits could be targeted for improvement in wheat breeding programs.

Evaluation of the anti-depressant potential of metformin in conditioned defeat model in golden Syrian hamsters

Background: Depression is a prevalent mood condition that has an impact on daily functioning. Globally, depression affects 264 million people. The current pharmacotherapy of depression has a lot of shortcomings. Therefore, there is a need to explore newer therapy that alleviate the symptoms of depression. Metformin was found to possess antioxidant potential and hypothesized to decrease the levels of branched-chain amino-acids essential for tryptophan uptake (precursor for serotonin synthesis). The study was designed to validate the efficacy of metformin as an anti-depressant in conditioned defeat model in male golden Syrian hamsters using open field test (OFT), forced swim test (FST) and Serum serotonin levels. Methods: After obtaining IAEC approval, the study was carried out using 8 golden Syrian hamsters each that were randomly assigned to four groups. The disease control group received 1mL normal saline, positive control was given fluoxetine 12 mg/kg, two groups of metformin 240 mg/kg given pre-insult and post-insult. The variables assessed on every third day included OFT and FST. Following the behavioral tests, serotonin-ELISA was done. To analyse the outcomes, appropriate statistical tests were applied. Results: On standardization, the model was established to a 16-day model. Further, results highlighted a significant difference in OFT, FST and serotonin levels with the metformin group and fluoxetine compared to disease control (p<0.001). However, no significant difference was observed between the fluoxetine and metformin groups (p>0.05), signifying the comparable results. Conclusions: Metformin (240 mg/kg) alleviated the depressive symptoms by modulating both behavioral and serotonin levels.

High prevalence of alpha thalassemia in the tribal community of the western part of India! Reality or myth? Can simple hematology parameters; MCV and MCH act as screening tools at birth?

Background: The majority of adult tribal subjects in the western part of India, show microcytic hypochromic red cells, and borderline anemia with a normal iron profile, suggesting a high prevalence of thalassemia in this population. Methods: The current study was designed to perform qualitative (to screen for Hb Bart’s) and quantitative (to estimate percentage of Hb Bart’s) hemoglobin electrophoresis with modification of the method, to evaluate the prevalence of ? thalassemia and to determine gene frequency of ?+ thal gene. Furthermore, the present study also aimed to evaluate common hematology parameters like MCV and MCH as screening tools to suspect ? thalassemia at birth. Results: Based on hemoglobin electrophoresis, the prevalence of ? thalassemia in all its forms was found to be 66.66%. The estimated gene frequency for ?+ thal was found to be 0.7453 and based on that, the extrapolated prevalence of ? thalassemia was 93.52% (55.55% homozygous and 37.97% heterozygous). MCV<100 fl and MCH<31 pg were found to be reliable screening tools to predict ? thalassemia at birth in full-term uncomplicated pregnancy. Conclusions: Tribal community in the western part of India bears a very high prevalence of ? thalassemia, it’s a reality and not a myth. Simple hematological parameters like MCV (<100 fl) and MCH (<31 pg) measured at birth can prove to be cost-effective surrogate markers for ? thalassemia. Large scale study using confirmatory genetic analysis is required to validate the findings.

Post-COVID Syndrome: The Stranger Ghost of Culprit COVID-19

Background: Post-COVID syndromes are the most abundant sequel of coronavirus disease of 2019 (COVID-19) infection, which affects millions of people around the whole world. There is a significant difference observed during the acute phase as well as during the post-COVID period between patients hospitalized with (alpha, delta, or omicron) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant. In the present scenario, when most people are vaccinated, COVID-19 disease is less likely, but the remnants of previous COVID-19 infections are still a vast health burden. Materials and methods: This prospective, observational, comparative, and analytical study included a total of 3,840 COVID-19-infected patients who visited the hospital. We included 1,150 patients of alpha variants, 1,845 patients of delta variants, and 815 patients of omicron variants, from June 2020 to November 2020, March 2021 to July 2021, and January 2022 to May 2022, respectively. All medical data of the study population, including hospital stay and vaccination status, were collected, and all patients were followed up for 6 months of duration. All collected data were compiled and analyzed to compare the post-COVID thrombotic and other events among different variants of COVID-19. Results: Patients infected during the delta variant are the most symptomatic at onset (higher prevalence of fever, dyspnea, cough, myalgia, headache, or gastrointestinal problems) than those infected with the alpha or omicron variant (p < 0.01). A total of 2,830 patients (7.48%) [1,520 (82.38%) of delta variant, 598 (73.37%) of omicron variant, and 712 (60.34%) of omicron variant] developed post-COVID syndrome during their follow-up period out of 3,220 enrolled patients and the difference was statistically significant when compared among variants (p < 0.05). In this study, the highly prevalent post-COVID syndrome was mucormycosis (11.41%), followed by new-onset diabetes (9.89%), pulmonary fibrosis (7.67%), ischemic heart disease (6.46%), brain stroke (3.29%), and other thromboembolic disorders (2.37%). Conclusion: COVID-19-associated onset symptoms during the delta variant were more severe and highly prevalent, while neurological symptoms (aguesia and anosmia) were more common during the alpha variant. Patients infected with the delta variant of COVID-19 are more prone to develop post-COVID-associated complications with minimal risk in the omicron variant and intermediate risk in the alpha variant. Long COVID-19 requires specific attention for management, irrespective of the SARS-CoV-2 variant.

Eating Behaviour and Body Mass Index of Patients with Severe Mental Illness Attending a Tertiary Hospital, Kochi, Kerala.

Background: Persons with severe mental illness are at increased risk of overweight and obesity both from the illness itself and from its treatment. Purpose: This study aimed to examine the eating behaviour and Body Mass Index (BMI) of patients with severe mental illness and to correlate these two variables. Methods: This descriptive cross sectional study was conducted at the psychiatry outpatient department of a tertiary hospital, Kochi, among 100 patients with severe mental illness who reported for follow up. Patients were interviewed individually after ethical procedures, using Personal information schedule and Three Factor Eating Questionnaire Revised-18, a standardized measure of eating behaviours. Anthropometric measurements were taken and BMI was calculated as per the WHO guideline for Asians. Results: The mean age and BMI of the sample were 49.5± 15.24 and 26.08 ± 4.79 kg/m2 respectively. Cognitive restraint was found to be the most frequently used eating behaviour (48%). Only 39% of the subjects had normal body weight. Overweight and obesity were observed in 39% and 19% respectively. BMI was positively correlated with uncontrolled eating (r=0.244, p<0.015), emotional eating (r=0.223, p<0.026) and eating behavior total score (r=0.293, p<0.003). Uncontrolled eating was high in patients who are non-vegetarian, taking thyroid medications and who reported parental obesity (p<0.05). Stepwise linear regressions revealed parental obesity as the most significant predictor of BMI (F=4.198, p<0.002). Conclusion: The chronic mentally ill require counseling and education about the role of eating behaviours in overweight and obesity and the ways of reducing body weight.

Functional Outcome of Open Latarjet Procedure in NonAthletic Middle-Aged Patie

@#Introduction: The movement and steadiness of the shoulder joint is due to both the dynamic and static stabilisers. Recurrent anterior shoulder instability is common due to the Bankart lesion or the Hill Sachs lesion. The bone loss and soft tissue failure due to these lesions causing instability is well compensated by Latarjet procedure which acts by triple blocking effect of the bone graft, the sling effect of the conjoint tendon of subscapularis and the ligament of the coracoacromial ligament stump. Materials and methods: Middle-aged patients with recurrent anterior shoulder dislocation and a mid-range instability on clinical assessment with an isolated glenoid bone loss of 20% or Bankart lesion with engaging Hill Sachs lesion were selected for the study. The surgical procedure included a subscapularis split to expose the glenoid. The coracoid graft harvested was prefixed with Kirschner wires and placed flush over the glenoid ensuring no medial or lateral overhang and fixed with 4.0mm cancellous screws with the washer. The functional outcome was measured with the ROWE score and ASES score and the movements were evaluated. Results: A total of 24 patients fulfilled the inclusion criteria. Post-operatively at final follow-up, the mean ROWE score was 97.08 ±8.45 and the mean ASES score was 94.4±9.10. One patient had screw breakage as a complication and another had restriction of movement which was managed with physiotherapy. Conclusion: Open Latarjet is an effective procedure for recurrent anterior shoulder instability in non-athletic middleaged patients as a excellent functional outcome was achieved with this technique. We therefore recommend open Latarjet as an alternative to arthroscopic treatment in developing countries where patient affordability and the availability of the resources are the issues.

Intrastromal voriconazole: An adjuvant approach for recalcitrant mycotic keratitis

Purpose: To evaluate the efficacy of intrastromal voriconazole for the management of fungal keratitis not responding to conventional therapy. Methods: Patients having microbiologically proven fungal keratitis with poor response to 2 weeks of conventional topical therapy were included in the study. After obtaining informed consent, an intrastromal injection of voriconazole was administered around the ulcer. Response to treatment in the form reduction in the size of the ulcer and infiltration was recorded on regular follow-ups. Results: Out of a total of 20 patients, 14 responded to intrastromal treatment and resolved, whereas six patients progressed to perforation. Mean resolution time was 35.5 � 9.2 days. The most common organism isolated was Fusarium in six patients while Aspergillus and Mucor were isolated in two each. The causative organism could not be isolated in eight patients. The size of the ulcer at presentation and height of hypopyon were found to be significant risk factors associated with treatment outcomes. Conclusion: Intrastromal voriconazole as an adjuvant therapy appeared to be effective in treatment of fungal keratomycosis not responding to conventional therapy, thus, reducing the need for therapeutic or tectonic keratoplasty.

Expression Enhancement Of Trastuzumab In Cho Cells Using Codon Optimization And Promoter Selection For Mammalian Expression Vector

Trastuzumab is recombinant humanized monoclonal IgG antibody used in the treatment of metastatic breast cancer. It blocks the overexpression of tyrosine kinase Her 2 family receptors and downregulation of pathways. Genetic optimizations like gene optimization and expression vector optimization are the key elements to enhance monoclonal antibody expression. Expression vector optimization includes major parameters like selection of right promoters, poly A tail selection of genome integrating elements. Codon optimization is gene designing approach without affecting the amino acid sequence of the protein. Current research work involves development of codon optimization algorithm for trastuzumab heavy and light chain gene and comparative analysis of expression in different vectors.

Cross-country transport and isolation and identification of Streptococcus pneumoniae by use of alternate sources of blood supplemented media among laboratories in India

Background: The isolation of S. pneumoniae (Sp) depends on specimen integrity / transport, media and expertise. The non-availability of sheep blood agar poses a challenge in identification of colonial morphology and identification in India. Methods: Laboratories processed swabs containing either pure Sp or Sp in mixed cultures with a second (confounding) bacterium shipped across the country in cold conditions. Duplicate set of swabs was shipped back to the central laboratory to assess the impact of shipping on culture viability. The identical swab was cultured on sheep, human blood and one additional agar plate used in the laboratory. Results: 46/60(77%) of cultures containing only Sp were correctly identified. In specimens where Sp was present in mixed culture, the proportion of isolates in which Sp was correctly identified varied, with most variability attributed to the particular confounding organism rather than the media. There was no discernible impact of temperature-controlled (4-6°C) transport on the isolation of Sp from culture swabs. Conclusions: The study clearly elucidates the ability of laboratories for isolation of S. pneumoniae on human blood agar in resource limited settings. The results highlight the difficulties inherent in correctly identifying pathogens in mixed cultures in needs improvement using standardized tests across the study centers. The study also reaffirms the ability to transport biological specimens over long geographical distances without loss.

BRAFV600E mutation in hairy cell leukemia: A single-center experience

Background: BRAFV600E mutation has been reported as a unique genetic lesion of hairy cell leukemia (HCL), a subset of which lacks this lesion and shows adverse outcomes. Aims: To determine the prevalence of BRAFV600E in HCL from our center and derive clinicopathological correlation, if any. Materials and Methods: A 9-year retrospective analysis of 46 consecutive cases of HCL diagnosed on morphology and immunophenotyping was done. Stained smears were used as samples for amplification refractory mutation system polymerase-chain reaction using fluorescent primers for mutation detection. Results: BRAFV600E mutation was detected in 41/46 patients (89.1%) while absent in control samples of chronic lymphocytic leukemia. Cases mimicking HCL-variant clinically or immunophenotypically too showed the presence of this mutation. HCL with mutated BRAF presented at a younger age. No statistical difference in blood counts, tumor load, and immunophenotype patterns existed among BRAF mutated and unmutated group. Nine patients (45%) with mutated BRAF had residual disease following treatment with cladribine. Conclusion: BRAFV600E mutation analysis has a definitive role in the diagnosis of HCL.

Pros & cons of some popular extreme weight-loss diets

Obesity has now become a huge public health issue not only in the developed world but also in developing countries. In view of the health hazards associated with obesity and more importantly for cosmetic reasons, many people, particularly the youth, have started resorting to 'extreme' weight-loss diets to achieve a rapid reduction in weight. These extreme diets are either very low in carbohydrate or very low in fat. Such extreme diets not only make the diet unbalanced but also have safety issues. Moreover, these are not sustainable in the long run. The weight that is lost is regained within a short period of time when people go off these extreme diets. This explains why the popularity of most extreme diets peaks as well as wanes rapidly. Instead of resorting to such extreme diets, correction of obesity is best achieved with balanced, healthy, nutritious diets which are low in calories, combined with adequate physical activity (exercise). Motivational counselling can also help people to initiate weight loss and sustain this weight loss over longer periods of time.

Validating the pachychoroid disease spectrum using multimodal imaging

Pachychoroid disease spectrum has garnered considerable interest and has been discussed in detail in recent literature. It refers to a group of retinal and choroidal disorders, namely pigment epitheliopathy, central serous chorioretinopathy, neovasculopathy, and polypoid choroidal vasculopathy, all arising from a thickened choroid and hyperpermeable large choroidal vessels. We describe a case which had simultaneous presentation of multiple disorders on the pachychoroid spectrum. Multimodal findings in this patient have been described in this report. The presence of pachychoroid should prompt thorough imaging since coexistence of multiple disorders can potentially change the management and follow-up schedule of these patients.

Molecular genetics of BCR-ABL1 negative myeloproliferative neoplasms in India

Introduction: Over the past decade, we have moved on from a predominantly morphological and clinical classification of myeloproliferative neoplasms (MPN) to a more evolved classification that accounts for the molecular heterogeneity that is unique to this subgroup of hematological malignancies. This usually incorporates mutations in Janus kinase 2 (JAK2), MPL, and calreticulin (CALR) genes. In this manuscript, we report the frequency of these mutations in a cohort of Indian patients at a tertiary cancer center. Materials and Methods: One hundred and thirty cases of MPN were included in this study. These cases were diagnosed and classified based on the World Health Organization 2008 criteria. JAK2 and MPL mutations were detected using high sensitivity allele-specific polymerase chain reaction using fluorescent labeled primers followed by capillary electrophoresis. A subset of JAK2 and CALR mutations were assessed using a fragment length assay. Results: Among the MPN, we had 20 cases of polycythemia vera (PV), 34 cases of essential thrombocythemia (ET), and 59 of myelofibrosis (MF). JAK2, MPL, and CALR mutations were mutually exclusive of each other. Seventeen cases were categorized as MPN unclassifiable (MPN-U). JAK2p.V617F and MPL mutations were present in 60% (78 of 130) and 5.3% (7 of 130) of all MPN. All the PV cases harbored the JAK2 p.V617F mutation. A total of 23.8% (31 of 130) of patients harbored CALR mutations. CALR exon 9 mutations were detected in 60.8% (14 of 23) and 50% (5 of 10) of JAK2 and MPL negative MF and ET cases, respectively. MPN-U cases included three JAK2 p.V617F positive, two MPL p.W515 L, and 12 CALR positive cases. Ten different types of CALR indels (8 deletions and 2 insertions) were detected of which Type I and Type II mutations were the most common, occurring at a frequency of 45.1% (14 of 31) and 22.5% (7 of 31), respectively. Discussion and Conclusion: We report frequencies of JAK2 p. V617F, MPL exon 10 and CALR mutations in 130 patients similar to those reported in western literature. These mutations carry not only diagnostic but also prognostic relevance.

A rare case of unilateral diffuse melanocytic proliferation

A 67-year-old woman presented with metamorphopsia in the right eye. Leopard mottling was seen temporal to the fovea oculus dexter with corresponding hyper- and hypo-autofluorescent lesions on fundus autofluorescence. Spectral domain-optical coherence tomography revealed hyperreflective dots in the retinal pigment epithelium and choroid with subretinal fluid (SRF). Intravitreal bevacizumab was administered with which SRF resolved, albeit with increase in the areas of mottling. The patient was diagnosed to have metastatic ductal carcinoma of the right breast. It is important to bear in mind that the well-known entity of bilateral diffuse uveal melanocytic proliferation can rarely present unilaterally.

Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014–2016: Study for monitoring antimicrobial resistance trend report

Background: The emergence of antibiotic resistance among bacterial pathogens in the hospital and community has increased the concern to the health-care providers due to the limited treatment options. Surveillance of antimicrobial resistance (AMR) in frequently isolated bacterial pathogens causing severe infections is of great importance. The data generated will be useful for the clinicians to decide empiric therapy on the local epidemiological resistance profile of the antimicrobial agents. This study aims to monitor the distribution of bacterial pathogen and their susceptibility pattern to the commonly used antimicrobial agents. Materials and Methods: This study includes Gram-negative bacilli collected from intra-abdominal, urinary tract and respiratory tract infections during 2014–2016. Isolates were collected from seven hospitals across India. All the study isolates were characterised up to species level, and minimum inhibitory concentration was determined for a wide range of antimicrobials included in the study panel. The test results were interpreted as per standard Clinical Laboratory Standards Institute guidelines. Results: A total of 2731 isolates of gram-negative bacteria were tested during study period. The most frequently isolated pathogens were 44% of Escherichia coli (n = 1205) followed by 25% of Klebsiella pneumoniae (n = 676) and 11% of Pseudomonas aeruginosa (n = 308). Among the antimicrobials tested, carbapenems were the most active, followed by amikacin and piperacillin/tazobactam. The rate of extended-spectrum beta-lactamase (ESBL)-positive isolates were ranged from 66%–77% in E. coli to 61%–72% in K. pneumoniae, respectively. Overall, colistin retains its activity in > 90% of the isolates tested and appear promising. Conclusion: Increasing rates of ESBL producers have been noted, which is alarming. Further, carbapenem resistance was also gradually increasing, which needs much attention. Overall, this study data show that carbapenems, amikacin and colistin continue to be the best agents available to treat drug-resistant infections. Thus continuous monitoring of susceptibility profile of the clinically important Gram-negative pathogens is of great importance to guide effective antimicrobial therapy.

In silico and In vitro activity of ceftolozane/tazobactam against pseudomonas aeruginosa collected across Indian hospitals

Ceftolozane/tazobactam is a novel antimicrobial agent with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens. In this study, we determined the antimicrobial susceptibility for a total of 149 clinical isolates of P. aeruginosa for the most commonly used antimicrobials including the new agent ceftolozane/tazobactam (C/T). Broth microdilution was performed to determine the minimum inhibitory concentration against various antimicrobials including C/T. Among the ?-lactam/?-lactamase inhibitor, overall susceptibility was 67%, 55% and 51% for C/T, Piperacillin/Tazobactam (P/T) and Cefoperazone/Sulbactam, respectively. The variations in the susceptibility rates were noted among the three different ?-lactam/?-lactamase inhibitors. Interestingly, 33% susceptibility was noted for C/T against isolates that were resistant to P/T, indicating the higher activity of C/T. This finding suggests about 33% of the P/T-resistant isolates can still be treated effectively with C/T. C/T could be a better alternative for the treatment of ESBL-producing organism, and thereby usage of higher antimicrobials can be minimised.

Liquid biopsy: emergence of a new era in personalized cancer care

The most successful treatment for cancer involves identifying druggable, biological markers for targeted therapy. In the clinical setting, surgical removal of tumors is the only procedure for identifying such targetable molecules. Shed from tumor cells, these markers are also present in circulating blood, albeit in very negligible amounts. Liquid biopsy is a procedure performed on a blood sample to look for such circulating cancer markers cells or pieces of nucleic acid from the tumor. The procedure shows promise in revolutionizing personalized cancer treatments. Here we briefly review the technique, characterization, and its utilization in clinics