Search

Nimbolide, a triterpenoid extracted from the flowers of the neem tree (Azadirachta indica), was found to have antiproliferative activity against some cancer cell lines. Treatment of cells with 0.5-5.0 microm concentrations of nimbolide resulted in moderate to very strong growth inhibition in U937, HL-60, THP1 and B16 cell lines. Flow cytometric analysis of U937 cells showed that nimbolide treatment (1-2.5 microm) resulted in cell cycle disruption by decreasing the number of cells in G0/G1 phase, with initial increases in S and G2/M phases. Cells exposed to a higher dose of nimbolide for a longer period displayed a severely damaged DNA profile, resulting in a remarkable increase in the number of cells in the sub-G1 fraction, with a reciprocal decrease of cells in all phases. Quantification of the expression of phosphatidylserine in the outer cell membrane showed that doses of nimbolide higher than 0.4 microm exerted remarkable lethality, with over 60% of cells exhibiting apoptotic features after exposure to 1.2 microm nimbolide. The antiproliferative effect of nimbolide and its apoptosis-inducing property raise hope for its use in anticancer therapy by enhancing the effectiveness of cell cycle disruption. [ABSTRACT FROM AUTHOR]

Primary tumor of falciform ligament is exceedingly uncommon. So far, seven cases of Perivascular Epithelioid Cell tumor (PECom), a recently described histological entity with characteristic perivascular tumor cell arrangement and expression of muscle and melanocytic marker by the cells, have been reported in literature. Here, we report a case of PEComa of falciform ligament, which presented with a huge abdominal lump. Pre-surgical CT scan of abdomen was uninformative regarding the nature and organ of origin of the tumor. On laparotomy, it was surprisingly found to arise from the falciform ligament, and this was easily removed. Histopathological diagnosis confi rmed PEComa. There was no recurrence of disease after two years of follow up. [ABSTRACT FROM AUTHOR]

Achilles tendon injury has been increasing over recent years due to a variety of causes. The injury of the Achilles tendon is a disabling condition, which is difficult to treat if there is a gap or defect between the two ends of the disrupted tendon. Patients with a rupture of the Achilles tendon should be operated without delay. Most of the people in our country use flat pan in the latrine, which are at a same level of the toilet floor. Surface of the toilet pan breaks down and cause sharp cut. Some of the cases of open tendon injuries occur due to road traffic accident, cut by broken glass and also assault. It is generally accepted that surgical repair of fresh ruptures of the Achilles tendon gives excellent results. Objective of the study was to find out the evaluation of the results of primary repair of Open tendo-achilles injury (OTAI). This prospective study was done in the department of Casualty of Mymensingh Medical College Hospital, Bangladesh in the period of Octy 2021 to June 2022. Patients who came with OTAI in casualty department were selected randomly. All cases were selected as OTAI, without associated injury of other leg muscles, posterior tibial artery and nerve within 12 hours. All patients underwent primary end to end repair by Modified Kessler's method. Evaluation of the results of primary repair of OTAI were carried out and were find out the common causes of injury, age and sex incidence, level of injury and to proposed a protocol for treating such cases in comfortable, cheap and convenient way for the patients. Operations were done at Casualty operation theatre (COT). Then 48 patients were followed up at the Department of Casualty. Among them 43(89.58%) of patients were able to stand on tip toes, 4(08.33%) of patients were not stand on tip toes of affected foot unsupported but able to stand on tip toes supported, 1(02.08%) of patients failed to stand on affected foot unsupported due to severe infection and wound gap. Final result were Excellent - 29(60.0%), Good - 14(30.0%), Fair - 4(8.0%), Poor - 1(2.0%). Repair of OTAI is not difficult but early diagnosis, proper surgical toileting, meticulous repair; adequate post-operative management is the key of success. So, the result of this study, treatment protocol can be followed, which is easy for surgeon and convenient and cheap for the patients.

Anchorage-independent triple-negative breast cancer (TNBC) cells exhibit elevated levels of the tryptophan (TRP) catabolizing enzyme tryptophan 2,3-dioxygenase 2 (TDO2) compared to the same cells grown in two-dimensional culture. Tracing of 13C11-TRP demonstrated that anchorage-independent culture and/or inflammatory cytokines that activate nuclear factor kappa-light-chain-enhancer of activated B (NFκB) increase TRP catabolism and production of downstream catabolites such as kynurenine (KYN), which activate the aryl hydrocarbon receptor (AhR). TDO2 expression is heterogeneous within TNBC cell lines. To determine the function of TDO2, both pharmacologic inhibition and genetic manipulation were conducted. TDO2 knockdown revealed a compensatory increase in indoleamine 2,3-dioxygenase 1 (IDO1), a non-homologous TRP catabolizing enzyme, indicating that dual inhibition of these two enzymes is necessary to reliably block TRP catabolism. Thus, we tested a newly developed TDO2/IDO1 dual inhibitor, AT-0174, and found that it effectively inhibits TNBC TRP catabolism. Furthermore, AT-0174 treatment or AhR inhibitor significantly decreased TNBC anchorage-independent survival, invasive capacity, and expression of mesenchymal genes and protein, while exogenous KYN increased invasion through AhR-mediated ZEB1 expression. Thus, dual inhibition of TDO2/IDO1 may prove efficacious against TNBC progression.

Although refrigerated storage slows the metabolism of volunteer donor RBCs, cellular aging still occurs throughout this in vitro process, which is essential in transfusion medicine. Storage-induced microerythrocytes (SMEs) are morphologically-altered senescent RBCs that accumulate during storage and which are cleared from circulation following transfusion. However, the molecular and cellular alterations that trigger clearance of this RBC subset remain to be identified. Using a staining protocol that sorts long-stored SMEs (i.e., CFSE high ) and morphologically-normal RBCs (CFSE low ), these in vitro aged cells were characterized. Metabolomics analysis identified depletion of energy, lipid-repair, and antioxidant metabolites in CFSE high RBCs. By redox proteomics, irreversible protein oxidation primarily affected CFSE high RBCs. By proteomics, 96 proteins, mostly in the proteostasis family, had relocated to CFSE high RBC membranes. CFSE high RBCs exhibited decreased proteasome activity and deformability; increased phosphatidylserine exposure, osmotic fragility, and endothelial cell adherence; and were cleared from the circulation during human spleen ex vivo perfusion. Conversely, molecular, cellular, and circulatory properties of long-stored CFSE low RBCs resembled those of short-stored RBCs. CFSE high RBCs are morphologically and metabolically altered, have irreversibly oxidized and membrane-relocated proteins, and exhibit decreased proteasome activity. In vitro aging during storage selectively alters metabolism and proteostasis in SMEs, targeting these senescent cells for clearance.

Background Gallbladder carcinoma (GBC) has deleterious outcomes, but due to its reduced incidence in Western countries, there is a paucity of data on this disease. Here we report the outcomes of a retrospective analysis of resectable gallbladder cancer from a tertiary cancer centre in eastern India. The primary objective of this study is to evaluate the overall survival (OS) and relapse-free survival (RFS) rates among patients with resectable GBC. Methods A retrospective analysis was carried out on patients who underwent radical surgery between 2007 and 2022 and received various neoadjuvant and adjuvant chemotherapy methods. Patients who had adjuvant chemoradiotherapy concurrently or who did not receive adjuvant therapy were excluded. All the baseline clinicopathological characteristics were retrieved from electronic medical records. The survival data were collected from records of follow-up visits as well as telephonic calls to the patients who were lost to follow-up. Simple proportions were used for baseline characteristics, and the Kaplan-Meier method was used for survival analysis. Results A total of 161 patients were identified, and data were captured from electronic medical records. The included patients' ages ranged between 26 and 80 years, with a median age of 56 years. Among the participants, 103 were female (64%) and 58 (36%) were male. Among the 161 patients, the median number of lymph nodes harvested was nine (ranging from one to 43), and only three patients were margin-positive. The tumour, nodes, and metastasis (TNM) distributions were as follows: pT2 in 111 patients (70.25%), pT3 in 44 patients (27.85%), and pT4 in three patients (1.90%). The nodal statuses were pN0 in 91 patients (61.9%), pN1 in 51 patients (34.69%), and pN2 in five patients (3.4%). The majority (64%) received single-agent capecitabine, 27% received gemcitabine-based platinum doublet therapy, and 4.3% received neoadjuvant therapy. Of the full sample, 2.4% received concurrent adjuvant chemo plus radiation therapy, and three patients did not receive any adjuvant therapy. Additionally, among the 161 patients, 34.16% had a relapse, with 47% being local and 52% being distant relapses. The median follow-up was 49 months (interquartile range (IQR) 23-71 months). The 24-month RFS rate was 67.1% (SD+/- 4.3%), and the 24-month OS rate was 78.1% (SD+/- 4.1%). Conclusion Our data, which is from one of the largest samples from India, show that resectable gallbladder cancer has very good outcomes after radical surgery and adjuvant chemotherapy. There was a higher proportion of T2 and node-negative disease, which could have led to better survival compared to published literature., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Tata Medical Center-Institutional Review Board (TMC-IRB) issued approval (EC/WV/TMC/29/24). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Das et al.)

Some transgender youth are treated with gonadotropin-releasing hormone agonists (GnRHa) followed by testosterone or estradiol, which may impact bone mineral density (BMD). This cross-sectional study of transgender youth (n = 56, aged 10.4-19.8 years, 53% assigned female at birth [AFAB]) utilized total body dual-energy x-ray absorptiometry to evaluate BMD Z-scores, and associations between GnRHa duration, body mass index (BMI), and BMD. Participants on GnRHa alone (n = 19, 14 assigned male at birth [AMAB], 5 AFAB) at the time of the study visit were 13.8 [12.8, 15.3] (median [IQR]) years old, had been on GnRHa for 10 [5.5, 19.5] months, and began GnRHa at age 12 [10.4, 12.6] years. Total body BMD Z-score for individuals on GnRHa monotherapy was -0.10 [-0.8, 0.4] (AFAB, female norms) and -0.65 [-1.4, 0.22] (AMAB, male norms). AFAB participants (n = 21) on testosterone were age 16.7 [15.9, 17.8] years, had been on testosterone for 11 [7.3, 14.5] months, and started testosterone at age 16 [14.8, 16.8] years; total body BMD Z-score -0.2 [-0.5, 0] (male norms) and 0.4 [-0.2, 0.7] (female norms). AMAB participants (n = 16) were age 16.2 [15.1, 17.4] years, had been on estradiol for 11 [5.6, 13.7] months, and started estradiol at age 16 [14.4, 16.7] years; total body BMD Z-score -0.4 [-1.1, 0.3] (male norms) and -0.2 [-0.7, 0.6] (female norms). BMD Z-score was negatively correlated with GnRHa duration (male norms: r = -0.5, P = .005; female norms: r = -0.4, P = .029) and positively correlated with BMI (male norms: r = 0.4, P = .003; female norms: r = 0.4, P = .004). In this cross-sectional cohort, total body BMD Z-scores were slightly below average, but lowest in the AMAB group on GnRHa monotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Biomanufacturing via microorganisms relies on carbon substrates for molecular feedstocks and a source of energy to carry out enzymatic reactions. This creates metabolic bottlenecks and lowers the efficiency for substrate conversion. Nanoparticle biohybridization with proteins and whole cell surfaces can bypass the need for redox cofactor regeneration for improved secondary metabolite production in a non-specific manner. Here we propose using nanobiohybrid organisms (Nanorgs), intracellular protein-nanoparticle hybrids formed through the spontaneous coupling of core-shell quantum dots (QDs) with histidine-tagged enzymes in non-photosynthetic bacteria, for light-mediated control of bacterial metabolism. This proved to eliminate metabolic constrictions and replace glucose with light as the source of energy in Escherichia coli, with an increase in growth by 1.7-fold in 75 % reduced nutrient media. Metabolomic tracking through carbon isotope labeling confirmed flux shunting through targeted pathways, with accumulation of metabolites downstream of respective targets. Finally, application of Nanorgs with the Ehrlich pathway improved isobutanol titers/yield by 3.9-fold in 75 % less sugar from E. coli strains with no genetic alterations. These results demonstrate the promise of Nanorgs for metabolic engineering and low-cost biomanufacturing., (© 2023 Wiley-VCH GmbH.)

Purpose of Review: To report a series of patients with clinical and radiological features suggestive of posterior reversible encephalopathy syndrome (PRES) related to diverse etiologies emphasizing its pathophysiological basis., Recent Findings: Posterior reversible encephalopathy syndrome (PRES) may present with a broad range of clinical symptoms from headache and visual disturbances to seizure and altered mentation. Typical imaging findings include posterior-circulation predominant vasogenic edema. Although there are many well-documented diseases associated with PRES, the exact pathophysiologic mechanism has yet to be fully elucidated. Generally accepted theories revolve around disruption of the blood-brain barrier secondary to elevated intracranial pressures or endothelial injury induced by ischemia from a vasoconstrictive response to rising blood pressure or toxins/cytokines. While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imaging. Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. Diagnosis of PRES in some circumstances can be challenging and structural imaging may not be sufficient to distinguish it from other differential diagnostic considerations like ADEM. Advanced imaging techniques, such as MR spectroscopy or positron emission tomography (PET) can provide additional information to determine the diagnosis. Such techniques are more useful to understand the underlying vasculopathic changes in PRES and may answer some of the unresolved controversies in pathophysiology of this complex disease. Eight patients with PRES resulting from different etiologies varying from pre-eclampsia/eclampsia, post-partum headache with seizures, neuropsychiatric systemic lupus erythematosus, snake bite, Dengue fever with encephalopathy, alcoholic liver cirrhosis with hepatic encephalopathy, and lastly reversible cerebral vasoconstriction syndrome (RCVS). Additionally, a diagnostic dilemma between PRES and acute disseminated encephalomyelitis (ADEM) was notable in one patient. Some of these patients did not have or only very transiently had arterial hypertension. PRES may underlie the clinical conundrum of headache, confusion, altered sensorium, seizures, and visual impairment. PRES need not necessarily be always associated with high blood pressure. Imaging findings may also be variable. Both clinicians and radiologists need to familiarize themselves with such variabilities., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Legg-Calve-Perthes disease (LCPD) that starts after 8 years (late onset) usually follow more aggressive course and the long-term outcome is also poor. Treatment method of LCPD that will produce best results is controversial particularly if the patients are with late-onset presentation. This prospective study was conducted from January 2015 to January 2019 at Dhaka Medical College Hospital and Health N Hope Hospital, Dhaka, Bangladesh. We evaluated the radiographic outcomes for patients who had varus derotation femoral osteotomy (VDRO). We followed up 16 patients who had femoral varus osteotomy. All patients were above 8 years of age at clinical onset. The involvement of femoral epiphysis was in either in B or B/C in lateral pillar classification. All patients had MRI done to confirm radiological diagnosis and classification. The mean age was 9.5 years (range, 8 to 12 years). Final outcome was evaluated by using the Stulberg classification which was radiological. Important exclusion criteria were patient with bilateral involvement and requirement of femoral varus >30 degree. We had 81.25% of our patient with satisfactory outcomes. Among them there were Stulberg grade I, 0 cases; Stulberg grade II, 13 cases (81.25%); Stulberg III, 3 cases (18.75%), Stulberg IV and V both 0 case each. The surgical outcomes for varus derotation femoral osteotomy in late onset LCPD patients over 8 years old were showing the good results than other modalities of non surgical and surgical methods.

Phenolic compounds possess significant biological activity. Several pieces of research emphasize the medicinal importance of phenolic compounds, including diabetes. The present study investigated the α-glucosidase inhibitory activity of phenolic compounds reported from several plants. The phenolic compounds reported in different literature were collected. Molecular docking was carried out using AutoDock Vina. Various physicochemical properties such as size, LogP, molecular complexity, hydrogen bonding properties of phenolic compounds were correlated with the binding affinities. Furthermore, MD simulation was carried out to study the structural stability of the docking complexes. A total of 155 phenolic compounds were reported from different plants. Amentoflavone showed the strongest binding affinity with α-glucosidase, much more potent than reference acarbose. The binding energy showed a good correlation with the molecular complexity, hydrogen bond donor and acceptor property and heavy atom counts of the compounds. The polarity of the surface area also showed a positive correlation with the binding affinity of the compounds. The best docking phenolic compound, amentoflavone, showed stable binding affinity and conformation during the simulation period compared to apoprotein and acarbose-docking complex. The top ten phenolic compounds, including amentoflavone, showed considerable drug-likeness properties with fewer toxicity effects. The study suggests that the amentoflavone could be a potential therapeutic drug as an α-glucosidase inhibitor and help control postprandial hyperglycemia.Communicated by Ramaswamy H. Sarma.

The conventional technique of harvesting free non-vascularized fibular grafting is associated with different scale of morbidity and usually a long scar. We follow a technique that causes minimum interference to the surrounding soft tissues to harvest the desired length of fibula. This prospective study was performed at Department of Orthopaedics, Dhaka Medical College Hospital from January 2018 to December 2018. Thirty patients of average age 10.5 years (range 8 to 14 years) were taken up for the study. The fibula was harvested by two separate incisions, 1 cm each at proximal and distal extent of proposed length of graft after elevating the periosteum circumferentially using a periosteum elevator. Compression bandage and above knee plaster immobilization was applied that help to reduce hematoma formation. The mean follow up is 12 months. The patients were evaluated clinically and by radiology. Twenty nine patients showed good results. One patient had delayed wound healing resulting in fair result. This modified approach of harvesting fibula reduces donor site morbidity and is safer and easier than conventional approach.

Background: Trend analysis of bacteraemias caused by multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria helps to assess efficacy of infection prevention and control (IPC) practices. Data on the trends of MDR and XDR bacteraemias are lacking from cancer patients in India., Aims: To report antibiotic resistance rates over time in bacteraemias and to assess the effect of IPC practices where patient isolation facilities were limited on the rates and trends of MDR and XDR bacteraemias from a cancer centre in eastern India., Methods: A retrospective observational study was conducted in a specialist cancer hospital in India from 2011 to 2021. The study included both patients with haematological and solid organ malignancy. Data on blood cultures and surveillance culture samples were analysed. Blood cultures were processed using BACT/ALERT® (bioMérieux, Marcy-l'Étoile, France) and the identification and antibiotic susceptibilities of bacteria were performed using VITEK® 2 (bioMérieux, Marcy-l'Étoile, France). Surveillance cultures for MDR/XDR bacteria were performed on a subset of patients and processed based on a modified method described previously., Findings: 3rd-generation cephalosporin-resistant Gram negative bacilli were the commonest cause of MDR bacteraemia (57.6%) followed by carbapenem resistant organisms (CRO) (35.7%). Bacteraemias caused by vancomycin-resistant enterococci (VRE), meticillin-resistant Staphylococcus aureus (MRSA) and colistin-resistant Gram negative bacilli were responsible for 1.3%, 2.3% and 3.0% of laboratory confirmed bloodstream infections (BSI) respectively. The ranges of the rates of MDR/XDR BSI per 1000 in-patients during the study period were: MRSA (1-1.18), VRE (0-0.88), 3 rd generation cephalosporin-resistant Gram negative bacilli (10.10-20.32), CRO (5.05-13.07) and colistin-resistant Gram negative bacilli ( E. coli, Klebsiella, Pseudomonas aeruginosa, Acinetobacter spp (0-1.3). Surveillance cultures collected from a subset of patients showed ranges of MRSA detection in 0-2.11%, VRE in 1.67%-7.49%, 3 rd generation cephalosporin-resistant Gram negative bacilli in 55%-89.91% and carbapenem resistant Gram negative bacilli in 18.33%-31.11% of patients., Conclusion: This is one of few studies providing trend data for MDR/XDR bacteraemia rates among cancer patients in India over a decade. In a high prevalence setting it was possible to keep the rates of MDR/XDR bacteraemia controlled with IPC strategies and without adequate isolation facilities. The results are of potential interest to policy makers, IPC specialists and clinicians., (© 2023 Published by Elsevier Ltd on behalf of The Healthcare Infection Society.)

The tendo achilles is one of most important tendon in human body which often injured through direct trauma or indirect stress on a weakened tendon. Longer the duration after injury the injured parts likely to move apart, fibrosis and degeneration leading to difficulty in repair or reconstruction. Usually a phase of 4 weeks or more without specific treatment is regarded as chronic or neglected rupture. Different authors described many management protocols about the tendo achilles rupture but there is no procedure of choice for neglected rupture with long gap. Prospective case series of 21 patients of neglected tendo achilles rupture with long gap treated with flexor hallucis longus tendon (FHLT) transfer was taken for study from January 2019 to December 2020 in Mymensingh Medical College Hospital, Bangladesh. Average age of patients was 39.47 years with range 22-65 years. Fifteen (15) cases of traumatic rupture in this study with average age 32.66 years and pathologic 6 cases with average age 56.5 years were recorded. We grafted FHLT from channel by incising Henry's knot. Krackow et al.'s technique was followed for tendon mobilization and bone fixation. We made procedure simpler and cheaper; instead of using interference screw the sutured tendon pulled through the heel and anchored over rubber tube or button by Cole method. Post-operative complications were less with one patient with superficial infection which eventually recovered 3 cases of mild pain and 2 cases of numbness. Questionnaire for surgical outcome measure are satisfactory in 19 patients (90.47%). Final follow up AOFAS score at 6 month (91.61±5.41) was highly significant (p<0.001) in comparison to preoperative score (38.71±9.78). These are comparable to other study. Above mentioned scores indicate the reliability of the surgical system. But our study is a prospective case series with minimum cases. To establish the best procedure for neglected tendo achilles rupture with long gap we recommend further study with larger group and Randomized Controlled Trial (RCT) study among different procedure.

Elderly women are very much prone to develop fracture at neck of femur sustained by even minute trauma. Most of the cases are due to fall. Osteoporosis gives rise to this vulnerable condition. In developing countries like Bangladesh the women of rural areas are the prime victims mostly due to illiteracy. To assess the quality-of-life (QOL) of elderly women (>60 years) with untreated hip fractures in a rural areas in Mymensingh, Bangladesh is the objective of this study. This prospective study was done from January 2019 to December 2019 in Orthopaedics and Traumatology Department of Mymensingh Medical Hospital, Mymensingh, Bangladesh. Twenty-five elderly women with untreated fracture neck of femur were enlisted in this study. EuroQol (EQ-5D) was applied to assess the Quality of life of subjects before and after the situation. Twenty-five elderly women of healed operated neck of femur were included as comparison group, matched for age, economic condition and educational status among neighborhood people. So, sample size was fifty. Wilcoxon signed rank test and Mann-Whitney U test were applied to compare EQ-5D mean scores. Participants with hip fracture, 60% (15/25), 68% (17/25), 68% (17/25), 60% (15/25) and 92% (23/25) reported severe problems with mobility, pain, usual activity, self-care and anxiety respectively. The EQ-5D mean score among the elderly with fracture neck of femur was 0.198 (SD 0.14). It was low when compared with the same subjects before the occurrence of the event (Z-6.522, p<0.001) and as compared with the comparison group (Z-7.92 p<0.001). QOL scores assessed using EQ-5D index scores was poor among elderly women with untreated fracture neck of femur as compared with the healed operated comparison group. Vast majority of study participants in this study were reported severe problems like mobility, pain, usual activity and self-care and anxiety.

Purpose: Malignant melanoma (MM) is rare in India. Indian data on demography and treatment outcome on advanced MM is very limited in the literature., Materials & Methods: This is a retrospective study of advanced MM treated between January 2013 and December 2020. We evaluated the clinicopathologic features, mutational profiles, survival outcome and prognostic factors in advanced MM patients., Results: Out of a total 460 patients, 185 (42%) had metastatic disease at presentation and were enrolled in this study with a median age of 63 years (range: 28-93) and male:female ratio of 94:91. The mucosal primary was predominant ( n = 110, 59%) than cutaneous primary (38%) and anorectum was the most common site ( n = 84, 45%). Tumour mutational analysis was performed in 65 (35%) patients. BRAF mutations were detected in 12 patients and KIT mutations in 7 patients. Thirteen patients didn't have any mutations and 22 patients had mutations other than KIT & BRAF . Only 59 (32%) patients took any systemic treatment - immune checkpoint inhibitors (ICIs) in 17, temozolomide in 18 and paclitaxel/carboplatin in 18, tyrosine kinase inhibitors in 6 patients. After a median follow-up of 26 months (95% confidence interval (CI): 11.6-not reached), median progression-free survival (PFS) was 7.1 months (95% CI: 4.4-9.1) and median overall survival was 14.8 months (95% CI: 7.7-18.2 months). The use of ICI emerged as an only significant good prognostic factor ( p ≤ 0.001) for PFS, on multivariate analysis., Conclusion: Mucosal origin was more common than cutaneous primary with anorectum being the most common site. BRAF mutation was less as compared to published literature. Very few patients received systemic therapy and the use of ICI showed superior PFS., Competing Interests: None for each author., (© the authors; licensee ecancermedicalscience.)

Alstonia scholaris , Cardiospermum halicacabum , Hydrocotyle sibthorpioides , and Hypericum japonicum are important folk medicinal plants used by tribal communities of Bodoland region of Assam to treat helminth infections. Because of their ethnomedicinal values, the present study was designed to investigate the antioxidant, antiproliferative, and anthelmintic activities of the plants. The antioxidant activity was measured by total antioxidant capacity, total phenolics (TPC), total flavonoid (TFC), FRAP, DPPH, ABTS, and TBARS assay. Antiproliferative and apoptosis-inducing activities of plants were conducted in Dalton's lymphoma (DL) cells. Cells were treated for 24 h with different doses (25-200 mg/mL) of plant extracts. Anthelmintic study was conducted by treating the Paramphistomum sp. at different doses of plant extracts. Phytochemical and antioxidant studies showed rich TPC, TFC, and free radical scavenging activity in H. japonicum and H. sibthorpioides . Both the antiproliferative and anthelmintic bioassays showed a dose-dependent efficacy in all plants. H. japonicum showed the strongest anthelmintic activity (LC 50 0.21 mg/mL) followed by H. sibthorpioides (5.36 mg/mL), C. halicacabum (13.40 mg/mL), and A. scholaris (18.40 mg/mL). Evidently, H. sibthorpioides showed the strongest antiproliferative and apoptosis-inducing activities among all the plants. The study observed a positive correlation between the antioxidant properties and antiproliferative and anthelmintic activities of the plants. We, therefore, conclude that the phytocompounds present in the crude extracts along with antioxidant molecules may have combined effects contributing to the antiproliferative and anthelmintic activities of the plants., Competing Interests: Conflict of interestAuthors do not have any conflict of interest., (© Indian Society for Parasitology 2021.)

Pulmonary hypertension (PH) is a severe cardiopulmonary disease characterized by complement-dependent, fibroblast-induced perivascular accumulation and proinflammatory activation of macrophages. We hypothesized that, in PH, nanoscale-sized small extracellular vesicles (sEVs), released by perivascular/adventitial fibroblasts, are critical mediators of complement-dependent proinflammatory activation of macrophages. Pulmonary adventitial fibroblasts were isolated from calves with severe PH (PH-Fibs) and age-matched controls (CO-Fibs). PH-Fibs exhibited increased secretion of sEVs, compared with CO-Fibs, and sEV biological activity was tested on mouse and bovine bone marrow-derived macrophages (BMDMs) and showed similar responses. Compared with sEVs derived from CO-Fibs, sEVs derived from PH-Fibs (PH-Fib-sEVs) induced augmented expression of proinflammatory cytokines/chemokines and metabolic genes in BMDMs. Pharmacological blockade of exosome release from PH-Fibs resulted in significant attenuation of proinflammatory activation of BMDMs. "Bottom-up" proteomic analyses revealed significant enrichment of complement and coagulation cascades in PH-Fib-sEVs, including augmented expression of the complement component C3. We therefore examined whether the PH-Fib-sEV-mediated proinflammatory activation of BMDMs was complement C3 dependent. Treatment of PH-Fibs with siC3-RNA significantly attenuated the capacity of PH-Fib-sEVs for proinflammatory activation of BMDMs. PH-Fib-sEVs mediated proglycolytic alterations and complement-dependent activation of macrophages toward a proinflammatory phenotype, as confirmed by metabolomic studies. Thus, fibroblast-released sEVs served as critical mediators of complement-induced perivascular/microenvironmental inflammation in PH.

Background: Pyruvate kinase deficiency (PKD) is the most frequent congenital enzymatic defect of glycolysis, and one of the most common causes of hereditary non spherocytic hemolytic anemia. Therapeutic interventions are limited, in part because of the incomplete understanding of the molecular mechanisms that compensate for the metabolic defect. Methods: Mass spectrometry-based metabolomics analyses were performed on red blood cells (RBCs) from healthy controls ( n =10) and PKD patients ( n =5). Results: In PKD patients, decreases in late glycolysis were accompanied by accumulation of pentose phosphate pathway (PPP) metabolites, as a function of oxidant stress to purines (increased breakdown and deamination). Markers of oxidant stress included increased levels of sulfur-containing compounds (methionine and taurine), polyamines (spermidine and spermine). Markers of hypoxia such as succinate, sphingosine 1-phosphate (S1P), and hypoxanthine were all elevated in PKD subjects. Membrane lipid oxidation and remodeling was observed in RBCs from PKD patients, as determined by increases in the levels of free (poly-/highly-unsaturated) fatty acids and acyl-carnitines. Conclusion: In conclusion, in the present study, we provide the first overview of RBC metabolism in patients with PKD. Though limited in scope, the study addresses the need for basic science to investigate pathologies targeting underrepresented minorities (Amish population in this study), with the ultimate goal to target treatments to health disparities., Competing Interests: AD’A is a founder of Omix Technologies Inc. and Altis Biosciences LLC. AD’A is a consultant for Rubius Therapeutics and an advisory board member for Hemanext Inc. and FORMA Therapeutics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Roy, Cendali, Ooyama, Gamboni, Morton and D’Alessandro.)

Persicaria strigosa (R.Br.) Nakai. (Family Polygonaceae) is an important plant of Assam, having several ethnobotanical uses. Tribal communities consume leaf extracts to cure helminth infection. The present study investigated the antioxidant, phytochemicals, and anthelmintic activity of P. strigosa. Total phenolic and flavonoid contents were estimated following standard methods. Antioxidant properties were analyzed by TAC, FRAP, DPPH, ABTS, and TBARS assays. Anthelmintic activity of plant was investigated in Paramphistomum sp. treated with 5 mg/mL, and paralysis and death times were recorded. The most potent solvent extract was performed GC-MS analysis to identify the phytocompounds. Plant extract-treated parasites were further analyzed for biochemical changes. Additionally, molecular docking was performed to study the binding affinities between phytocompounds and enzymes. P. strigosa showed rich phenolics, flavonoids, and antioxidant properties. Ethyl acetate and methanolic extracts showed more powerful antioxidant properties than other extracts. In vitro anthelmintic study found ethyl acetate and diethyl ether the most active extracts. Treated parasites showed a significant decrease in enzyme activity. The highest inhibition was observed in AchE, followed by MDH, LDH, ALP, and ACP. GC-MS study identified 12 probable compounds from the ethyl acetate extract of P. strigosa. Molecular docking showed the strongest binding affinity between the phytocompounds and AchE enzyme (- 7.6 kcal/mol). Overall, compounds C6, C7, and C12 showed better binding affinity compared to other compounds. The in vitro helminth bioassays and biochemical analysis suggest Persicaria strigosa a possible anthelmintic agent. However, isolation and characterization of bioactive compound(s) may promise new drug candidates for helminth infections., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intramedullary nailing is a pillar in the treatment of femoral shaft fractures. But it is not possible in all cases especially in comminuted fractures. This study has been designed to explain the importance of Minimally Invasive Plate Osteosynthesis (MIPO) with the locking plate in the treatment of comminuted Femoral Shaft Fracture. Twenty (20) such patients were treated by MIPO and analysis has been done in this study to get fruitful result and to find out the effectiveness of this procedure who were admitted at Mymensingh Medical College Hospital, Mymensingh, a tertiary level hospital of Bangladesh from February 2018 to January 2019. Mean age of the patients were 49.20±14.41 years. Based on AO classification, there were 4, 8 and 8 patients belong to type A, B and C respectively. The union period for all the patients was in between 12 to 14 weeks. The mean union period was 12.90±1.997 weeks. Mean follow up period was 19.70±2.77 weeks. Mean full weight bearing period was 16.50±1.10 weeks. In Thoresen scoring system excellent result was 9(45%), good result was 10(20%) and fair result was 01(5%). Mal-alignment happened in two cases. However, delayed union and broken screws were found in two cases each of which was treated accordingly. Comminuted Femoral shaft fracture with MIPO procedure is more effective treatment than intramedullary nailing. Furthermore, mal-alignment is the basic complexity that must be taken away intraoperatively.

Danis-Weber type-B ankle fracture is one of the most common injuries in young and active individual. This fracture offers a considerable challenge to orthopedic surgeon. Though there are several options for treating such type of fracture, ORIF by Pre-contoured Distal Fibular Locking Plate is the preferred option in the recent years. This descriptive type of observational study was performed from July 2017 to June 2019 in NITOR. Thirty (30) patients, 22 male and 8 female with an average age of 39 years with Danis-Weber type-B ankle fracture underwent ORIF by Pre-contoured Distal Fibular Locking Plate for fractured fibula and ORIF by 4.0mm cannulated cancellous screw for fractured medial malleolus. All the patients were initially managed by analgesic and short leg posterior slab. Average follow up was 24 weeks. Final outcome was assessed by AOFAS score. The main cause of injury was RTA (56.67%). Mean operation time was 1.2 hours. Mean duration of Hospital stay was 16.43±1.73 days. Superficial infection was in 3.33% and skin necrosis in 3.33% patient. Mean duration of radiological healing was 12.73±0.39 weeks. At final follow up, mean dorsi flexion was 10.93°±0.357° and plantar flexion was 50.93°±0.357°. Ninety percent (90%) patient had no difficulties in walking on any surface; 96.67% patient had stable ankle hind foot; 86.67% patient had good. Ten percent (10%) had fair and 3.33% patient had poor alignment of foot. The mean score in this study was 88.67±2.31. Satisfactory outcome was observed in 86.67% patients and 13.33% had unsatisfactory results. On the basis of results in the present study, it can be concluded that treatment of Danis-Weber type-B ankle fracture by Pre-contoured Distal Fibular Locking Plate is an effective and reliable method.

Cellular death of bone due to impairment of the blood supply leading to collapse resulting in pain, and loss of joint function is known as avascular necrosis (AVN). The head of femur is the most common bone affected by avascular necrosis followed by talus and scaphoid. We evaluate the results of core decompression with non-vascularized fibular graft in avascular necrosis of femoral head. This quasi experimental study was done at Mymensingh Medical College Hospital, Dhaka Medical College Hospital and some other private hospitals of Bangladesh. The study includes patients who underwent core decompression and non-vascularized fibular grafting in avascular necrosis of femoral head from January 2017 to December 2018. In this study we evaluated total 20 patients and majority of the patients belongs to the group of 20-30 years. Out of 20 patients, 8 of them were unilaterally involved rest 12 had bilateral involvement. Out of 24 hips of bilateral involvement 4 were grade III and IV (Ficat and Arlet classification) therefore not included in the study. So, we study 28 hips only. The average success rate was 90% after core decompression and non-vascularized fibular bone grafting. Harris hip score of 60 on presentation had poorer outcome. Patients with less than 80 degrees of flexion had poorer outcome.

In adults, distal humerus fractures are infrequent and frequently intra-articular. Customarily encompass both medial and lateral columns. Operative management gives constructive outcomes. The aim of this study was to evaluate clinical outcome in intra articular distal humerus fractures in adults treated by different hardware. This prospective study consists of 20 purposively selected patients with intra articular distal humerus fractures treated by surgical intervention with different hardware who were admitted to Mymensingh Medical College and Hospital, Bangladesh in between November 2016 to October 2018. Surgical approaches were standard dorsal with or without olecranon osteotomy. The mean age of the patients was 32.3 years, range between 18-55 years. The maximum patients i.e. 85% were between 18-45 years. Seventy percent (70%) of the cases admitted were due to Road traffic accident (RTA). Most of the patients were males 14(70%) with right upper limb was involved in 13(65%) cases. Mean Mayo Elbow Performance Score was 81.5 post-operatively. According to Mayo Elbow Performance (MEP) score clinical outcome was excellent in 20%, good in 50%, fair in 25% and poor in 10% of patients. Distal humerus fractures are censorious in nature. Proper anatomical articular reconstruction and stable fixation by surgical intervention helps in fruitful results.

Distal tibial fractures are difficult to manage as the bone is subcutaneous with depleted muscular cover; the consequent decreased vascularity leads to complications. Minimal invasive plate osteosynthesis (MIPO) is a very good option for managing this type of fractures. This study was carried out to evaluate the outcome of patients treated with distal tibial locking plate by MIPO technique. Twenty patients with distal tibia fractures treated with distal tibial anatomical locking plate were prospectively studied from July 2013 to December 2016. The result was excellent in 18(90%) of patients i.e. 18 patients had an AOFAS score of 90 or greater out of a possible 100 points. The mean score was 94.28; the mean time for radiological union was 20.1 weeks with a range of 16 to 30 weeks. We encountered superficial infection in 02 (10%) of our patients which were managed with dressings and appropriate antibiotics. Two patients had union with valgus angulation of less than 5°. No malunion was detected. One patient had ankle stiffness requiring extensive physiotherapy to regain range of movement. Plate removal was done in 4 cases. MIPO technique is a good fixation method for fractures distal third of tibia, preserving blood supply & fracture hematoma.

Background: The use of medicinal plants for general wellbeing and disease treatment is a common practice among tribal communities of Kokrajhar districts of Assam. However, little works have been done to study the pharmacological aspect of the plants., Objectives: The present study intends to study the antioxidant and antiproliferative properties of selected medicinal plants used by the tribal communities of the Kokrajhar district of Assam since ancient times., Methods: Five traditionally important medicinal plants, namely, Cassia fistula, Citrus grandis, Lindernia crustacea, Sacciolepis myosuroides, and Zingiber zerumbet were investigated for antioxidant, antiproliferative (cytotoxic) and apoptosis-inducing potential in the malignant cancer cell line. Phytochemical content, such as phenolic and flavonoid content, were estimated following standard protocol. The methanolic extract of plants was investigated following the phosphomolybdate method (TAC), FRAP, DPPH, ABTS, and TBARS assays. Antiproliferative activities of the plants were carried out by MTT assay in DL and PBMC cells. The apoptotic study was carried out following the acridine orange and ethidium bromide staining method and fluorescent microscopic imaging. Based on the significant (P≤0.05) high apoptotic inducing potential of the plant and to further dissect the molecular mode of action, including downstream biological action, major phytochemicals derived from L. crustacea were investigated for its prospective binding affinity with anti-apoptotic cancer target proteins., Results: Antioxidant studies by FRAP, DPPH, ABTS, and TBARS assay revealed that all five plants contain considerable free radical scavenging activity. C. fistula showed the strongest free radical scavenging activity while the fruit peel extract of C. grandis showed poor activity. The overall antioxidant activities of plants such as TAC, FRAP, DPPH, ABTS, and TBARS may be arranged in decreasing activity as C. fistula > Z. zerumbet > L. crustacea > S. myosuroides > C. grandis. MTT based cell proliferation study showed that all the plants extract significantly (P≤0.05) inhibited cell viability with negligible cytotoxicity (~5-12%) in normal cells. Moreover, L. crustacea showed promising antiproliferative and apoptosis-inducing ability against Dalton's lymphoma. It is worth mentioning that the major bioactive compounds of the most potent plant extract, L. crustacea interacted with anti-apoptotic proteins (cancer target) with higher affinity and the results are compared with reference inhibitors., Conclusion: It is worth noting that these plants have the potential to consider for further scientific studies in different cell lines and animal models. Furthermore, isolation and characterization of bioactive compound(s) may promise the discovery of new and valuable drugs candidate to tackle various human diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Transverse colon, owing its origin to midgut and hindgut and harbouring a flexure at both ends, continues to pose a surgical challenge. When compared to the rest of the colon, transverse colon adenocarcinoma is relatively uncommon. These cancers usually present late and lie in close proximity to the stomach, omentum, and pancreas. Adequate lymphadenectomy entails dissection around and ligation of the middle colic vessels. Hence, resectional surgery for transverse colon carcinoma is considered difficult. This is more so because of the variation of arterial and venous anatomy. From this perspective, the surgeon is tempted to perform a more radical operation like extended right or left hemicolectomy to secure an adequate lymphadenectomy. Such a cancer has also been dealt with a more limited transverse colectomy with colo-colic anastomosis. For all these reasons, patients with transverse colon adenocarcinoma were excluded from randomised trials which compared laparoscopic resection with traditional open operation. Surgical literature is yet to establish a definite operation for transverse colon cancer and the exact procedure is often dictated by surgeon's preference. This is primarily because this is an uncommon cancer. The rapid adoption of laparoscopic operation favoured extended colectomy as transverse colectomy can be difficult by minimally invasive technique. However, in the recent past, cohort studies and meta-analyses have shown equivalent oncological outcome between transverse colectomy and extended colectomy. It is time to resurrect transverse colectomy and consider it equivalent to its radical counterpart for cancers around the mid-transverse colon., Competing Interests: The authors declare no conflicts of interests for this article., (© 2020 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

Variety of conditions may be responsible for low back pain but lumber spinal canal stenosis is an important cause of low back pain. Lumber spinal canal stenosis usually presents with low backache with neurogenic claudication and shortness of walking distance in adult patient. Surgical management of lumbar spinal canal stenosis by decompression surgery is effective method. This prospective interventional study was performed in patient with clinical features like low back pain with radicular pain, neurogenic claudication, signs of root compression, positive MRI findings attending in department of Orthopaedic Surgery Mymensingh Medical College Hospital and Private Hospital from July 2016 to June 2019. Thirty patients were evaluated among those 20(66.6%) were 50 years and above. The mean age was 47.5±1.6 years. Male to female ratio was roughly 8:1. Almost all of the patients had low backache with radiation to the back of the thigh and leg with motor weakness (60%). About 66.6% of the patients had sensory deficit and 83.3% had neurogenic claudication. Majority (80.0%) of the patients at presentation had a suffering of 12 or >12 months. The mean duration of suffering was 14.7±5.1 months. About 55% of the patients were able to perform heel-walking and 36.0% tip-toe walking. Nearly 57% of the patients had sensory deficit along the distribution of 1st sacral nerve and 53.3% along the distribution of lumber 5 nerves. Diagnosis shows that 16.6% of patients had L4 lesion, 50% L5, 10.0% patients had L4 & L5 and 46.6% S1. Laminectomy was done in 26.6% of patients, laminectomy and disectomy in 33.3% and laminectomy, discectomy & foraminal decompression in 40.0% of patients. Twenty five (83.5%) of patients was free from symptoms. Eighty percent (80.0%) of patients shows minimal disability and 20.0% moderate disability on the basis of Oswestry Disability Index, while by MacNab criteria, most (80%) of patients was excellent, 10% good and another 10% fair. Repeated measure ANOVA statistics showed that mean Oswestry score decreased significantly from 54.5% at baseline to 22% at the end of 1 year (p<0.001).

Background: Taurine is an antioxidant that is abundant in some common energy drinks. Here we hypothesized that the antioxidant activity of taurine in red blood cells (RBCs) could be leveraged to counteract storage-induced oxidant stress., Study Design and Methods: Metabolomics analyses were performed on plasma and RBCs from healthy volunteers (n = 4) at baseline and after consumption of a whole can of a common, taurine-rich (1000 mg/serving) energy drink. Reductionistic studies were also performed by incubating human RBCs with taurine ex vivo (unlabeled or 13 C 15 N-labeled) at increasing doses (0, 100, 500, and 1000 μmol/L) at 37°C for up to 16 hours, with and without oxidant stress challenge with hydrogen peroxide (0.1% or 0.5%). Finally, we stored human and murine RBCs under blood bank conditions in additives supplemented with 500 μmol/L taurine, before metabolomics and posttransfusion recovery studies., Results: Consumption of energy drinks increased plasma and RBC levels of taurine, which was paralleled by increases in glycolysis and glutathione (GSH) metabolism in the RBC. These observations were recapitulated ex vivo after incubation with taurine and hydrogen peroxide. Taurine levels in the RBCs from the REDS-III RBC-Omics donor biobank were directly proportional to the total levels of GSH and glutathionylated metabolites and inversely correlated to oxidative hemolysis measurements. Storage of human RBCs in the presence of taurine improved energy and redox markers of storage quality and increased posttransfusion recoveries in FVB mice., Conclusion: Taurine modulates RBC antioxidant metabolism in vivo and ex vivo, an observation of potential relevance to transfusion medicine., (© 2020 AABB.)

The study assessed the economic, environmental and sustainability issues of organic shrimp farming in Bangladesh. Following stratified random sampling technique, 60 farmers were interviewed from several villages of Assasuni upazila under Satkhira district. The study revealed that productivity of organic shrimp per hectare was 383 pound and benefit cost ratio was 1.91 which meant that organic shrimp farming was highly profitable. Educational level of household head, gher size and knowledge on organic shrimp production had positive and significant influence in adopting organic shrimp production by the farmers. Cause-effect-mitigation analysis pointed out that organic shrimp farming could mitigate the adverse effects on environment caused by traditional shrimp farming. Appropriate climate and environment for organic shrimp culture was found as major strength and comparative profitability than traditional shrimp production was found as major opportunity of organic shrimp production. The study confirmed sustainability of organic shrimp production from the standpoint of consuming energy, protecting environment, economic feasibility and social/political equity. The study recommends that farmers should be trained to follow the work instructions and principles of organic shrimp production and the application of good management practices (GMPs) should be ensured for reducing the disease outbreak risk., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Giant-cell tumor constitutes 4-20% of all primary bone tumors in south East Asian population. They are benign locally aggressive bone tumour first described by cooper in 1818. These tumors occur predominantly in meta-epiphyseal region. Most often they are located around the knee joint. Although most of the tumors are diagnosed on plain radiograph alone, varying CT and MRI presentations of these tumors are essential to narrow down the differentials has an extended pre operative assessment.

This study was conducted in the department of Surgery, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2016 to December 2017 and performed to assess the negative appendicectomy on histopathology followed by clinically and laboratory investigations based diagnosed acute appendicitis. To perform this prospective study 200 patients with pain in right iliac fossa of both sexes randomly selected and were evaluated by history, clinical examination, laboratory investigations (USG, CBC) and scoring system. Among 200 patients male 124 and female 76 under went appendicectomy 36 were histopathologically normal appendix. Over all negative appendicectomy (NAR) 18%, among them 14.5% (18/124) were male & 23.67% (18/76) were female.