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Arsenic tops the list of priority list of hazardous substances 2022. People are frequently exposed to the environmental pollutant metalloid arsenic through their food, water, air, and soil. Arsenic is famous for its toxic effects. However, arsenicals have recently gained attention due to promising clinical trials for the treatment of acute myeloid leukemia. Presently numerous studies on arsenic's anticancer effects have been done. So a review was conducted on the use of arsenicals as poison and medicine. Arsenical was used as a powerful medicine in the BC era. But arsenical became famous as "the King's Poison" and "the Poison of the King" due to its use as poison. But the development of Marsh’s Test in the 18th century led to a decrease in the use of arsenicals as poison. In the 18th century, arsenicals were used as medicine to treat a variety of diseases such as fever, rheumatism, psoriasis, and syphilis. The development of antibiotics, new, safer chemotherapeutic agents, and radiotherapy halted its use as medicine. The dose and form of arsenicals make them medicine or poison. Many literary works reveal that arsenic's journey as “medicine” and “poison” is still ongoing in the twenty-first century.
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Background/Aims@#Gastric varices (GV) are present in 25% of cirrhotic patients with high rates of rebleeding and mortality. Data on endoscopic ultrasound (EUS)-guided treatment in severe liver disease (model for end stage liver disease sodium [MELD-Na] >18 and Child-Turcotte-Pugh [CTP] C with GV) are scarce. Thus, we performed a retrospective comparison of endoscopic glue injection with EUS-guided therapy in cirrhotic patients with large GV. @*Methods@#A retrospective study was performed in the tertiary hospitals of India. A total of 80 patients were recruited. The inclusion criteria were gastroesophageal varices type 2, isolated gastric varices type 1, bleeding within 6 weeks, size of GV >10 mm, and a MELD-Na >18. Treatment outcomes and complications of endoscopic glue injection and EUS-guided GV therapy were compared. @*Results@#In this study, the patients’ age, sex, liver disease severity (CTP, MELD-Na) and clinical parameters were comparable. The median number of procedures, injected glue volume, complications, and GV obturation were better in the EUS group, respectively. On subgroup analysis of the EUS method (e.g., direct gastric fundus vs. paragastric collateral [PGC] coil placement), PGC coil placement showed decreased coil requirement, less injected glue volume, decreased luminal coil extrusion, and increased successful GV obturation. @*Conclusions@#EUS-guided treatment is more efficient and safer, and requires a smaller number of treatment sessions, as compared to endoscopic treatment in severe liver disease patients with large GV. Furthermore, PGC coil placement increases the complete obliteration of GV.
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Hydrogel posses a degree of flexibility very similar to natural tissues, due to their significant water content. Thus they find potential biomedical applications owing to their excellent bio-compatibility, bio degradability and non toxicity. The main highlight of the work is that it is taking naturally occurring polymers such as agar and Chitosan for the synthesis of hydrogel. Different compositions of Chitosan/Agar hydrogels were formulated and optimised with respect to pH sensing, Urea absorption and dye adsorption. Chitosan/Agar hydrogels are found to be suitable and a potential candidate for several agricultural and bio medical applications
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Cancer, which is the uncontrolled growth of cells, is the second leading cause of death after heart disease. Targeting drugs, especially to specific genes and proteins involved in growth and survival of cancer cells, is the prime need of research world-wide. Indole moiety, which is a combination of aromatic-heterocyclic compounds, is a constructive scaffold for the development of novel leads. Owing to its bioavailability, high unique chemical properties and significant pharmacological behaviours, indole is considered as the most inquisitive scaffold for anticancer drug research. This is illustrated by the fact that the U.S. Food and Drug Administration (FDA) has recently approved several indole-based anticancer agents such as panobinostat, alectinib, sunitinib, osimertinib, anlotinib and nintedanib for clinical use. Furthermore, hundreds of studies on the synthesis and activity of the indole ring have been published in the last three years. Taking into account the facts stated above, we have presented the most recent advances in medicinal chemistry of indole derivatives, encompassing hot articles published between 2018 and 2021 in anticancer drug research. The recent advances made towards the synthesis of promising indole-based anticancer compounds that may act via various targets such as topoisomerase, tubulin, apoptosis, aromatase, kinases, etc., have been discussed. This review also summarizes some of the recent efficient green chemical synthesis for indole rings using various catalysts for the period during 2018-2021. The review also covers the synthesis, structure‒activity relationship, and mechanism by which these leads have demonstrated improved and promising anticancer activity. Indole molecules under clinical and preclinical stages are classified into groups based on their cancer targets and presented in tabular form, along with their mechanism of action. The goal of this review article is to point the way for medicinal chemists to design and develop effective indole-based anticancer agents.
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In our previous studies, we have demonstrated the association of certain variants of the thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (TG) genes with congenital hypothyroidism. Herein, we explored the mechanistic basis for this association using different in silico tools. The mRNA 3'-untranslated region (3'-UTR) plays key roles in gene expression at the post-transcriptional level. In TSHR variants (rs2268477, rs7144481, and rs17630128), the binding affinity of microRNAs (miRs) (hsa-miR-154-5p, hsa-miR-376a-2-5p, hsa-miR-3935, hsa-miR-4280, and hsa-miR-6858-3p) to the 3'-UTR is disrupted, affecting post-transcriptional gene regulation. TPO and TG are the two key proteins necessary for the biosynthesis of thyroid hormones in the presence of iodide and H2O2. Reduced stability of these proteins leads to aberrant biosynthesis of thyroid hormones. Compared to the wild-type TPO protein, the p.S398T variant was found to exhibit less stability and significant rearrangements of intra-atomic bonds affecting the stoichiometry and substrate binding (binding energies, ΔG of wild-type vs. mutant: ‒15 vs. ‒13.8 kcal/mol; and dissociation constant, Kd of wild-type vs. mutant: 7.2E-12 vs. 7.0E-11 M). The missense mutations p.G653D and p.R1999W on the TG protein showed altered ΔG (0.24 kcal/mol and 0.79 kcal/mol, respectively). In conclusion, an in silico analysis of TSHR genetic variants in the 3'-UTR showed that they alter the binding affinities of different miRs. The TPO protein structure and mutant protein complex (p.S398T) are less stable, with potentially deleterious effects. A structural and energy analysis showed that TG mutations (p.G653D and p.R1999W) reduce the stability of the TG protein and affect its structure-functional relationship.
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Background/Aims@#The pathogenesis of gastrointestinal (GI) symptoms in patients with type 2 diabetes mellitus (T2DM) is yet to be delineated clearly.Serotonin, a monoamine neurotransmitter, resides primarily in the gut and plays a vital role in GI system. However, no study has been documented the role of serotonin and serotonin transporter gene (SLC6A4) polymorphism in the development of GI symptoms in T2DM patients. @*Methods@#Three hundred diabetes patients attending diabetes clinic at Postgraduate Institute of Medical Education and Research, Chandigarh, and matched healthy controls were enrolled for this study. Plasma from collected blood sample was used for serotonin measurement by enzyme-linked immunosorbent assay method and buffy coat was used for isolation of DNA by phenol chloroform method.Serotonin transporter gene polymorphism was analyzed by polymerase chain reaction method. @*Results@#The frequency of short allele (S) and SS genotype was significantly higher in patients with T2DM than controls and was associated with increased risk of T2DM. The frequency of LS genotype showed an association with protection from the disease. Regarding GI symptoms, 78.2% of patients with constipation showed LL and LS genotypes, and 97.7% of patients with diarrhea had SS genotype. The patients without GI symptoms did not show any association of gut motility with genotype. Furthermore, serotonin was significantly higher in diabetic patients who belonged to SS genotype compared to LS or LL genotype and who presented with diarrhea. @*Conclusion@#SS genotypes are prone to develop diarrhea because of faster gut motility resulting from higher serotonin levels as compared to LS and LL genotype in T2DM patients.
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Background/Aims@#The pathogenesis of gastrointestinal (GI) symptoms in patients with type 2 diabetes mellitus (T2DM) is yet to be delineated clearly.Serotonin, a monoamine neurotransmitter, resides primarily in the gut and plays a vital role in GI system. However, no study has been documented the role of serotonin and serotonin transporter gene (SLC6A4) polymorphism in the development of GI symptoms in T2DM patients. @*Methods@#Three hundred diabetes patients attending diabetes clinic at Postgraduate Institute of Medical Education and Research, Chandigarh, and matched healthy controls were enrolled for this study. Plasma from collected blood sample was used for serotonin measurement by enzyme-linked immunosorbent assay method and buffy coat was used for isolation of DNA by phenol chloroform method.Serotonin transporter gene polymorphism was analyzed by polymerase chain reaction method. @*Results@#The frequency of short allele (S) and SS genotype was significantly higher in patients with T2DM than controls and was associated with increased risk of T2DM. The frequency of LS genotype showed an association with protection from the disease. Regarding GI symptoms, 78.2% of patients with constipation showed LL and LS genotypes, and 97.7% of patients with diarrhea had SS genotype. The patients without GI symptoms did not show any association of gut motility with genotype. Furthermore, serotonin was significantly higher in diabetic patients who belonged to SS genotype compared to LS or LL genotype and who presented with diarrhea. @*Conclusion@#SS genotypes are prone to develop diarrhea because of faster gut motility resulting from higher serotonin levels as compared to LS and LL genotype in T2DM patients.
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Background: A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do; wounds that do not heal within three months are often considered chronic. Aim of this study the efficacy of topical use of collagen granules in wound healing.Methods: In this prospective study, a total of 60 patients were divided into two groups, according to type of dressing i.e. for group A patients collagen granules were used and for group B patients normal saline dressing was used. Collagen granules used for this study was Medfil II.Results: The Mean ulcer size at day 1 in group A was 16.29 cm2 with a SD of 6.07cm2. In Group B, the mean ulcer size at day 1 was 14.73 cm2 with a SD of 6.37 cm2. The Z value is 0.93 and p value is >0.5. This is comparable but statistically not relevant.Conclusions: The use of Collagen Granules dressing accelerated the rate of wound healing in chronic ulcers In this study authors found that the rate of wound healing was significantly better in using Collagen Granules but after 2 weeks.
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Background: Trauma is a major cause of mortality worldwide. This study is aimed at the patterns of chest trauma, their presentation and the outcome of management.Methods: A prospective study of trauma patients admitted to a tertiary care centre was carried out the clinical history, physical examination and outcome of management recorded in a predesigned proforma were analysed with SPSS 15 and the patients were followed up in the surgical department.Results: A total of 638 patients were admitted. 57 patents were identified with chest trauma, 43 (75%) were males and 14 (24.56%) were females. The age range was from 3-78 years and the most affected age was in the range of 20 to 39 years. Blunt injury constituted 82.4% while road traffic accident was responsible for 70.1%. The average time taken between accident and admission was 11 hours 12 minutes while the average duration of hospital stay was 11 days. The injury pattern mainly included rib fracture and hemopneumothorax. The mortality rate was 1.75%.Conclusions: Most patients arriving at the hospital survived, requiring general resuscitation or simple tube thoracostomy with few complications. Mortalities from trauma and cause of death at the site of accident are often not accounted for due to non-presentation to the hospital and lack of autopsy for those who present.
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A Simple, rapid, specific, accurate, economical and precise UV spectrophotometric and RP-HPLC methods (inaccordance with ICH guidelines) were developed and validated for determination of Nortriptyline hydrochlorideand Pregabalin in tablet dosage form. The first method was based on Q - absorbance ratio, and absorbances ofboth drugs were determined at 239 nm (λmax of Nortriptyline Hydrochloride) and 235 nm (Iso-absorptive Point)when dissolved in methanol. It is found that Pregabalin does not have chromophoric group. To be UV-sensitive,it was compulsory to introduce chromophoric group in Pregabalin structure and make it UV-sensitive. This wasachieved by converting the primary amine group of Pregabalin through reaction with benzoyl chloride to formbenzoylated derivative of Pregabalin. Benzoylated Pregabalin was determined at 225 nm using UV-visiblespectrophotometer. The second method was based on RP-HPLC. The chromatographic separation was performedon an Inertsil ODS C18 column (250 x 4.6mmx 5 μm) with a mobile phase of 0.56 %w/v Sodium hexane sulphonicacid dissolved in water acetonitrile (50:50 %v/v, pH 4.5 adjusted with Glacial Acetic Acid) at flow rate of 1.0mL/min with DAD detection wavelength at 210 nm. Retention times of Nortriptyline Hydrochloride andPregabalin were 7.3894 min and 4.0506 min, respectively. Beer-Lambert’s law obeyed the concentration rangeof 2-12 μg/mL for Nortriptyline Hydrochloride and 10-60 μg/mL for Pregabalin. The results indicated that bothspectrophotometric and RP-HPLC methods were linear, accurate, precise and robust with RSD values less than0.2% and % recovery was within the standard limits (99 - 102%).
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Background: Injuries and violence are among the most prominent public health problems in the world. Objective was to study the epidemiological profile of injuries in urban and urban slum areas of Rajkot city, India.Methods: A community based study was conducted in Rajkot city with sample size of 540 households. Total 30 clusters (society) were selected from 805 notified societies including 20 clusters from urban areas and 10 clusters from urban slum areas of Rajkot city. From identified cluster, 18 households were selected to achieve targeted sample size 540. All injuries reported among all household members in the last 12 months were included in the study. A total of 2,367 persons of all ages were interviewed.Results: The prevalence of injury was 14% among 2,367 study participants. Almost all injuries (99.1%) were unintentional in nature. The leading causes of injures were falls (49.2%) and road traffic accidents (RTAs) (35.7%). Significant numbers of injuries were reported among males (p<0.01). The males reported RTAs (46.9%) and females reported falls (64.2%) as a common type of injury (p<0.01). Lower limb (70.1%) was the most commonly affected body part and road (38.4%) was the most common place of injury occurrence. Average money spent by injured person was Rs. 7,000. Only 11.3 % study participants had health insurance.Conclusions: Injury prevention priorities should be focused on the leading causes such as falls and RTAs to develop specific preventive strategies.
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Introduction: Adolescence is a period when individual starts coming up with their choices and develops personal lifestyle. This lifestyle includes unhealthy diet and physical inactivity which are the major risk factors of various non-communicable diseases of great public health importance like cardiovascular diseases, diabetes, obesity etc. Objective: To assess the pattern of dietary practices and physical activity among school going adolescents in Haldwani block of Nainital district. Material and Method: School based cross sectional study was done among 900 adolescents of 8th to 12th standard. Sample collected from 30 clusters/schools using simple random sampling. Results: Out of 900 students, majority were non-vegetarian. Daily intake of fruits and vegetable was observed among 31.9% and 73.3% of adolescents. Practice of eating junk food and meals outside home were seen more in urban adolescents. 55.6% of participants were found to be physically active, sedentary behavior was more common in urban area and adolescents studying in private schools.
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Objective: To study the five year trend of epidemiological and demographic characteristics ofdengue infections from year 2013 to 2017 among children upto 15 years. Methods: Thisstudy presents data from review of microbiology department records of samples for denguetesting with information supplied by clinicians on the investigation request form. Patientswere tested for NS1 Ag, IgM Ab or both. Results: Out of 4216 samples, 1072 (25.4%) werepositive for dengue. Positivity ranged from 44.1% in year 2013, 25.8% in 2015 to 16.1% inyear 2017. Most cases reported were among male (57.9%), from urban areas (77.9%) andRajkot district (75.7%). Reporting of dengue cases increased from July to November withpeak during October every year. Conclusion: Serum samples for dengue serology weremore commonly positive in July-September months during the study period, and in malechildren, and those from urban areas.
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Objective: Continuous thoracic epidural analgesia (TEA) is compared with erector spinae plane (ESP) block for the perioperative pain management in patients undergoing cardiac surgery for the quality of analgesia, incentive spirometry, ventilator duration, and intensive care unit (ICU) duration. Methodology: A prospective, randomized comparative clinical study was conducted. A total of 50 patients were enrolled, who were randomized to either Group A: TEA (n = 25) or Group B: ESP block (n = 25). Visual analog scale (VAS) was recorded in both the groups during rest and cough at the various time intervals postextubation. Both the groups were also compared for incentive spirometry, ventilator, and ICU duration. Statistical analysis was performed using the independent Student's t-test. A value of P < 0.05 was considered statistically significant. Results: C omparable VAS scores were revealed at 0 h, 3 h, 6 h, and 12 h (P > 0.05) at rest and during cough in both the groups. Group A had a statistically significant VAS score than Group B (P ≤ 0.05) at 24 h, 36 h, and 48 h but mean VAS in either of the Group was ≤4 both at rest and during cough. Incentive spirometry, ventilator, and ICU duration were comparable between the groups. Conclusion: ESP block is easy to perform and can serve as a promising alternative to TEA in optimal perioperative pain management in cardiac surgery.
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Minimally invasive atrial septal defect (ASD) closure is a commonly performed cardiac surgical procedure and has good outcome. We report an interesting chest X-ray showing pneumopericardium in a patient who underwent ASD closure using a minimally invasive approach.
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The brachial plexus consists of a network of nerves that innervates the upper limbs and its musculature. We report a rare formation of the lateral cord of the brachial plexus observed during the dissection of a 47-year-old male cadaver at the Department of Anatomy, Vardhman Mahavir Medical College, New Delhi, India, in 2016. The lateral cord was exceptionally long with twin lateral pectoral nerves and twin lateral roots of the median nerve. The proximal lateral root of the median nerve was thin in comparison to the medial root of the median nerve. The distal lateral root of the median nerve was thicker and followed an unusual course through the coracobrachialis muscle. In the lower third of the arm, the median nerve and the brachial artery-along with its vena comitans-spanned through the brachialis muscle. Surgeons, anaesthesiologists, radiologists and anatomists should be aware of such anatomical variations as they may result in neurovascular compression
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<p><b>PURPOSE</b>The aim of present study is to evaluate the outcome of bone marrow instillation at the fracture site in fracture of intracapsular neck femur treated by head preserving surgery.</p><p><b>METHODS</b>This study included 32 patients of age group 18-50 years with closed fracture of intracapsular neck femur. Patients were randomized into two groups as per the plan generated via www.randomization.com. The two groups were Group A (control), in which the fracture of intracapsular neck femur was treated by closed reduction and cannulated cancellous screw fixation, and Group B (intervention), in which additional percutaneous autologous bone marrow aspirate instillation at fracture site was done along with cannulated cancellous screw fixation. Postoperatively the union at fracture site and avascular necrosis of the femoral head were assessed on serial plain radiographs at final follow-up. Functional outcome was evaluated by Harris hip score.</p><p><b>RESULTS</b>The average follow-up was 19.6 months. Twelve patients in each group had union and 4 patients had signs of nonunion. One patient from each group had avascular necrosis of the femoral head. The average Harris hip score at final follow-up in Group A was 80.50 and in Group B was 75.73, which was found to be not significant.</p><p><b>CONCLUSION</b>There is no significant role of adding on bone marrow aspirate instillation at the fracture site in cases of fresh fracture of intracapsular neck femur treated by head preserving surgery in terms of accelerating the bone healing and reducing the incidence of femoral head necrosis.</p>
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A total of 1496 school children aged 8-18 years (79.1% boys) participated in this study. Prevalence of obesity and overweight was estimated by using three different growth standards. Revised IAP 2015 growth standards detected more obese and overweight children than WHO 2007 and IOTF standards.
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Background: The Integrated Child Development Services (ICDS) scheme has been operational for more than three decades in India. Objective: To evaluate the various aspects of the ICDS program in terms of inputs, process and outcome (coverage), utilization, and issues related to the ICDS program. Methods: A total of 130 Anganwadi centers (AWCs) were selected including 95 AWCs from rural areas and 35 AWCs from urban areas from April 2012 to March 2015, from 12 districts of Gujarat and the union territory of Diu. Information was collected for infrastructure, baseline characteristics of AWWs, provision, coverage and utilization of various ICDS services, and various issues related to program operation. Results: A majority of pregnant (94.7%) and lactating (74.4%) mothers, and adolescent girls (86.6%) were availing ICDS services. In 96.9% of the AWCs, a growth chart was available and 92.3% AWWs were using it accurately. A total of 14.9% children were underweight including 13.5% moderately and 1.4% severely malnourished children. Two-third (66.2%) children were covered by supplementary nutrition (SN). Only 14.6% of the AWCs reported 100% preschool education (PSE) coverage among children. More than half (55.4%) of the AWCs reported an interruption in supply during the last 6 months. Various issues were reported by AWWs related to the ICDS. Conclusion: The study has reported gaps in terms of infrastructure facility, different trainings, coverage, supply, and provision of SN, status of PSE activities in AWCs, and provision of different services to the beneficiaries.
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Impedance plethysmography (IPG) came into existence in 1940 as a result of Jan Nyboer’s pioneering work in the noninvasive assessment of central and peripheral blood flow. The technique got an impetus after introduction first-time derivative of the impedance for accurate determination of stroke volume (SV) and various cardiac intervals. Later, this signal was employed by Parulkar et al for estimation of blood flow index (BFI) and differential pulse arrival time (DPAT) in various segments of the extremity, which were adequate to detect the aortic and peripheral arterial blocks and estimate collateral circulation and distal arterial runoff. The technique was widely used for measurement of respiration and body water. All these applications have resulted into use of bioimpedance for body composition analysis and continuous monitoring of cardiac output as US Food and Drug Adminstration (FDA) approved technologies, which are being used worldwide. Physiological variability has added more value to this technique as single data acquisition gives variability in heart rate and SV (or peripheral blood flow). Morphology index thus derived is very useful in screening patients suspected with coronary artery disease (CAD). All these milestones are briefly described in this paper.