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Introduction: Bipolar disorder is a chronic, debilitating psychiatric disorder. Mood stabilizers and atypical antipsychotics are first line drugs for bipolar disorder. They have significant adverse effects. Aim: The study was conducted with an aim to evaluate the pattern of occurrence of Adverse Drug Reactions (ADRs) in the patients with bipolar disorder and to assess their causality, severity and preventability. Materials and Methods: A prospective and observational study - carried out in the psychiatry outpatient department of New Civil Hospital, Surat for 15 months. All patients diagnosed with bipolar disorder and receiving pharmacotherapy were included. Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale and Abnormal Involuntary Movement Scale (AIMS) were used for documenting ADRs and tardive dyskinesia, respectively. Assessment of causality, severity and preventability of recorded ADRs was done using Naranjo’s algorithm and WHO-UMC scale, modified Hartwig and Seigel Scale and modified Schumock and Thornton scale, respectively. Descriptive statistics was used (percentage, mean±standard deviation) for presentation of demographics and other numerical data; Chi Square test and Fisher’s exact test were used to assess association between variables. A p-value < 0.05 was considered significant. Results: A total of 703 ADRs were recorded from 175 patients. The most common ADRs observed were asthenia (11.95%) and sedation (10.24%). Majority of ADRs were mild on assessment with UKU scale. Mood stabilizers (59.46%) were most frequently associated with ADRs and lithium was most common single drug responsible. Upon causality assessment, majority of the reactions were probable (54.77% with WHO-UMC scale, and 56.33% with Naranjo’s algorithm). The association of results between the two scales was statistically significant (p

Key Clinical Message Uterine artery embolization demonstrated significant efficacy in the treatment of utero‐cervical cancer. This minimally invasive procedure holds promise as a valuable adjunct therapy, potentially offering improved outcomes and reduced morbidity in select cases. Further research is warranted to validate its broader clinical utility. Abstract Vaginal bleeding is a common complication of Cervical cancer that can be considered a critical emergency. Conventional hemostatic treatments may occasionally help reduce the bleeding but are not an effective long‐term solution. Uterine Artery Embolization, a minimally invasive intervention, can halt the bleeding, achieving hemostasis, while removing many of the complications that alternative interventions carry. We outline a case study of a patient with extensive vaginal bleeding who had uterocervical malignancy and talk about the benefits of uterine artery embolisation for therapeutic management.

Key Clinical Message Chikungunya encephalitis, though rare, warrants clinical attention due to its severe complications. Early identification and appropriate management are crucial for improved outcomes in patients with this rare manifestation of chikungunya virus (CHIKV) infection. Abstract CHIKV infection is commonly associated with fever and joint pains, but neurological complications such as encephalitis are rare. Here, we present a unique case of confirmed chikungunya encephalitis in a 12‐year‐old male exhibiting atypical neurological symptoms. The diagnostic journey involved comprehensive neuroimaging and serological investigations, revealing intriguing findings on magnetic resonance imaging and positive CHIKV RNA in serum and cerebrospinal fluid. We discuss the clinical presentation, radiological characteristics, and management strategies, emphasizing the importance of recognizing this uncommon neurological manifestation of CHIKV infection.

Background: Transversus thoracis muscle plane block (TTPB) and parasternal intercostal nerve block (PICNB) inhibit the anterior branches of intercostal nerves and potentially provide adequate analgesia after cardiac surgery. This study aimed to compare these two blocks for a reduction in postoperative opioid consumption after cardiac surgery., Methods: This randomized, single-blind trial included 60 adult cardiac surgical patients divided into three groups to receive ultrasound-guided TTPB (group T), PICNB (group P), or no block (group C) before surgery. All patients received standard anesthesia with intravenous etomidate, fentanyl, midazolam, and vecuronium. Postoperative fentanyl consumption in the first 24 hours was the primary outcome variable. Secondary outcomes were pain fentanyl consumption in 48 hours, intensity, analgesia duration, heart rate, mean arterial pressure, and complications., Results: The groups had similar baseline characteristics. The duration of analgesia was longer, while the intensity of pain and opioid consumption were statistically lower (p<0.01) in groups P and T compared to group C. The differences between groups P and T were not statistically significant. Fentanyl consumption in the first 24 hours was 284.00±37.61 µg, 293.00±35.11 µg, and 383.40±57.21 µg in groups P, T, and C, respectively. Other outcome variables were statistically similar among the groups., Conclusion: Both TTPB and PICNB produce equivalent and satisfactory postoperative analgesia, reducing the postoperative fentanyl use in 24 hours for patients undergoing elective cardiac surgery., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Ethics Committee, King George's Medical University, Lucknow. issued approval (1219/Ethics/2020). 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, Yadav et al.)

Monocyte-derived macrophages recruited to injured tissues induce a maladaptive fibrotic response characterized by excessive production of collagen by local fibroblasts. Macrophages initiate this programming via paracrine factors, but it is unknown whether reciprocal responses from fibroblasts enhance profibrotic polarization of macrophages. We identify macrophage-fibroblast crosstalk necessary for injury-associated fibrosis, in which macrophages induced interleukin 6 ( IL-6 ) expression in fibroblasts via purinergic receptor P2rx4 signaling, and IL-6, in turn, induced arginase 1 ( Arg1 ) expression in macrophages. Arg1 contributed to fibrotic responses by metabolizing arginine to ornithine, which fibroblasts used as a substrate to synthesize proline, a uniquely abundant constituent of collagen. Imaging of idiopathic pulmonary fibrosis (IPF) lung samples confirmed expression of ARG1 in myeloid cells, and arginase inhibition suppressed collagen expression in cultured precision-cut IPF lung slices. Taken together, we define a circuit between macrophages and fibroblasts that facilitates cross-feeding metabolism necessary for injury-associated fibrosis.

Introduction: Non-high-density lipoprotein cholesterol (non-HDL-C) levels can increase the cardiometabolic risk factors in patients with hypothyroidism, but the findings across studies have not been consistently conclusive. The aim of this study was to find the association between non-HDL-C and cardiometabolic risk factors in patients with hypothyroidism., Material and Methods: In this case-control study, a total of 120 subjects among which 60 diagnosed hypothyroidism patients and 60 age-matched healthy controls were enrolled, aged 30-65 years. Body mass index (BMI), waist circumference (WC), and systolic and diastolic blood pressures (SBP and DBP) were measured. Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), fasting blood sugar (FBS), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were estimated. Low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and non-HDL-C were calculated. A p-value of <0.05 was considered statistically significant., Results: Mean of BMI, WC, FBS, TSH, TC, TG, non-HDL-C, LDL-C, VLDL-C, SBP, and DBP were significantly elevated in cases compared to controls (p<0.001). However, the mean of T3, T4, and HDL-C were significantly reduced in cases compared to controls (p<0.001). Non-HDL-C has shown a significant positive correlation with age (r=0.345, p<0.01), TC (r=0.451, p<0.01), TG (r=0.269, p<0.05), LDL-C (r=0.402, p<0.01), and VLDL-C (r=0.269, p<0.05) among cases. However, non-HDL-C has shown a significant negative correlation with HDL-C (r=-0.330, p<0.05) among cases. Non-HDL-C significantly predicted cardiometabolic risk in patients with hypothyroidism (F(13,46)=3.500, p<0.001)., Conclusion: Non-HDL-C has shown a significant association with age and lipid abnormalities in patients with hypothyroidism. Non-HDL-C significantly predicts cardiometabolic risk factors in patients with hypothyroidism., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Integral Institute of Medical Sciences and Research issued approval IEC/IIMS&R/2023/63. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. 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, Khan et al.)

Introduction- Spindle cell neoplasm is a variant of squamous cell carcinoma. One of its subtypes is solitary fibrous tumor. Its occurrence in head and neck is very rare and rarer in hard palate. But if occurs, radical excision is the only choice as it has malignant potential but coverage of such large mid face defects imposes a challenge in front of a Plastic Surgeon as it demands both soft tissue coverage and skeletal support. Report of the case- A 33 year male presented to our department with swelling of left side face involving the anterior palate, maxilla, nose, and upper lip. With the help of the surgical oncology team, wide local excision of the neoplasm along with bilateral infrastructure maxillectomy, total rhinectomy, total upper lip resection and total hard palatectomy was done. This created large defect in the mid face which was covered with free anterolateral thigh flap. Biopsy was done which revealed the swelling as a solitary fibrous tumor of hard palate. All the margins were free of tumour. The flap settled well. Nostrils were secured with nasal stents. After 3 months, an expander was placed in forehead of the patient for future nasal reconstruction. After 3 months, nasal reconstruction was done using expanded forehead flap and costal cartilage. After 21 days flap detachment and insetting was done. White roll creation was also done. One more secondary procedure was done for flap thinning as patient had complain of nasal obstruction. After 6 months vascularised free fibula bone graft was introduced to reconstruct maxilla for future dental rehabilitation. The patient is in regular follow up and he is satisfied with the results. Discussion- Mid face defects involving perioral and nasomaxillar areas are very uncommon and require composite reconstruction. In such cases, microvascular free flap coverage is an irreplaceable option. Multiple stages might have to be done for further refinement. Conclusion- Reconstruction after oncological resection is always very demanding. With proper preoperative planning and skilled execution, the patient can be benefited functionally, aesthetically and psychosocially., Competing Interests: Competing interestsThe authors have no relevant financial or non-financial interests to disclose., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Owing to their great promise of high energy density, the development of safer lithium metal batteries (LMBs) has become the necessity of the hour. Herein, a scalable method based on conventional Celgard membrane (CM) separator modification is adopted to develop high-rate (10 mA cm ‒2 ) dendrite-free LMBs of extended cyclability (>1000 hours, >1500 cycles with 3 mA cm ‒2 , the bare fails within 50 cycles) with low over potential losses. The CM modification method entails the deposition of thin coatings of (≈6.6 µm) graphitic fluorocarbon (FG) via a large area electrophoretic deposition, where it helps for the formation of a stable LiF and carbon rich solid electrolyte interface (SEI) aiding a uniform lithium deposition even in higher fluxes. The FG@CM delivers a high transport number for Li ion (0.74) in comparison to the bare CM (0.31), indicating a facile Li ion transport through the membrane. A mechanistic insight into the role of artificial SEI formation with such membrane modification is provided here with a series of electrochemical as well as spectroscopic in situ/ex situ and postmortem analyses. The simplicity and scalability of the technique make this approach unique among other reported ones towards the advancement of safer LMBs of high energy and power density., (© 2023 Wiley‐VCH GmbH.)

Conjugated polymers with ethylene glycol side chains are emerging as ideal materials for bioelectronics, particularly for application in organic electrochemical transistors (OECTs). To improve the OECT device performance, it is important to develop an efficient synthetic strategy that will provide access to novel high-performing materials besides focusing on molecular design. While a lot of efforts are being devoted to designing of new polymers by modifying the glycol side chains, understanding how their nature affects the polymerization kinetics and eventually the polymer structure and properties is not known. In this work, we have studied the influence of the content of the ethylene glycol side chain and its linkage on the formation of the active Grignard monomer species upon Grignard metathesis in three thiophene derivatives. A strong dependence of the monomer's concentration on polymerization was noted in our study indicating that for synthesizing P3MEEMT, a high-performing OECT material, by Kumada catalyst transfer polymerization (KCTP) a minimum of 0.15 M monomer is needed. Furthermore, kinetic studies by GPC show uncontrolled polymerization behavior contrary to the controlled chain growth characteristics of the KCTP.

Background: Insulin resistance is often implicated as a risk factor of cell-mediated immune dysfunction in sepsis patients and results in poor clinical outcome. However, it is unclear whether early insulin resistance is contributory to T-cell dysfunction and poor clinical outcome in coronavirus disease 2019 (COVID-19) patients., Methods: Adult patients with moderate-to-severe or critically ill COVID-19 infection were included in this study. Serum samples were collected at the time of diagnosis for fasting plasma glucose, serum insulin, serum cortisol, and serum glucagon measurements, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated., Results: One hundred and twenty-six subjects with a mean (standard deviation) age of 49.6 (16.3) years were recruited in this study, and 62.4% (78 of 125 patients) were male. HOMA-IR was a predictor of inhospital mortality with the area under the receiver operating characteristics curve (AUROC) (95% confidence interval [CI] of 0.61 [0.49-0.73]). With a cutoff value of 1.91, sensitivity was 75.5% and specificity was 45.2%. Higher serum insulin was associated with higher survival with AUROC (95% CI) of 0.65 (0.53-0.76), and the best cutoff was 7.15, with a sensitivity and specificity of 62.1% and 64.5%. Serum cortisol was also a predictor of inhospital mortality with an AUROC (95% CI) of 0.67 (0.56-0.77)., Conclusion: An independent association between baseline serum cortisol and poor outcome in moderate-to-severe COVID-19 patients was observed. Hyperglycemia and HOMA-IR can also predict poor outcome in these patients with some accuracy., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 International Journal of Critical Illness and Injury Science.)

Background: An early warning score can be used to identify worsening in obstetric patients as they are more prone for deterioration. This study was conducted to evaluate and validate the performance of the modified early obstetric warning system (MEOWS) as a screening tool for early prediction of severe obstetric morbidity., Methods: This prospective observational study was conducted at obstetrics and gynaecology department, Tata Main Hospital, Jamshedpur, Jharkhand, India. A total of 1800 patients were included over a period of 10 month, from December 2021 to September 2022. Study population included all pregnant women admitted in labour room with > 28 weeks of gestation till 6 weeks postpartum. MEOWS charts were plotted for each patient, score calculated and documented at admission. Patients were categorized based on this score for further management, and follow-up was made till discharge. Outcome assessment was done in terms of ICU admission, length of hospital stays, obstetric morbidity, and maternal mortality. Correlation of each outcome with scoring was evaluated., Results: The sensitivity of MEOWS in predicting maternal morbidity was 72.91%, specificity 91.87%, positive predictive value 85.96%, and negative predictive value 83.24%. The area under receiver operator characteristic of MEOWS for prediction of maternal mortality was 0.79 (95% CI 0.75-0.82)., Conclusion: MEOWS helps in early recognition of obstetric morbidity even before signs, and symptoms become clinically evident. It is a useful tool for predicting adverse maternal outcome in pregnant women., Competing Interests: Conflict of interestNil., (© Federation of Obstetric & Gynecological Societies of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Competing Interests: Conflicts of interest: The authors have no conflicts of interest.

Mastitis is the most devastating economic disease in dairy cattle. Mastitis in dairy cattle frequently occurs during the dry period or during early lactation. Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus )are the main causative agents of mastitis in India. S. aureus can form microabscesses in the udder and develop a subclinical form of mastitis. This bacterial property hinders an effective cure during the lactation period. Antimicrobials used for treatments have a short half-life at the site of action because of frequent milking; thereforethey are unable to maintain the desired drug concentration for effective clearance of bacteria. We demonstrated the potential of ciprofloxacin-encapsulated nanocarriersthat can improve the availability of drugs and provide an effective means for mastitis treatment. These drug-loaded nanoparticles show low toxicity and slow clearance from the site of action. Antimicrobial activity against clinical strains of E. coli and S. aureus showed that the zone of inhibition depended on the dose (0.5 mg to 2 mg/mL nanoparticle solution from 11.6 to 14.5 mm and 15 to 18 mm). These nanoparticles showed good antimicrobial activity in broth culture and agar diffusion assay against bacteria.

Every medical student amidst COVID-19 missed out on an integral part of medical education which is interaction with patients as all the physical classes were postponed for months. Effective interaction with patients is the heart of medicine and it provides a synergistic effect on the delivery of high-quality care to the patient. However many medical students underestimate the art of communication. This article highlights the importance of basic communication skills; also encourages reflecting upon the whole experience and extracting the learning to apply to any further interactions., Keywords: communication; empathy; medical students; healthcare quality.

Objectives: Existing research on erector spinae plane block and intrathecal morphine in patients undergoing percutaneous nephrolithotomy surgery is limited., Methods: In this prospective, randomized study, 60 patients aged between 18 and 60 years were randomized into two groups (erector spinae plane block and intrathecal morphine). In the erector spinae plane block group, ultrasound-guided erector spinae plane block was performed, following which a mixture of 20 mL of 0.375% ropivacaine and 0.5 mcg/kg of clonidine was injected. In the intrathecal morphine group, 150 mcg preservative-free morphine with 2 mL of normal saline was administered intrathecally. The primary outcome was to evaluate the perioperative opioid consumption in the first 24 h. The secondary outcomes were to evaluate hemodynamic response to surgical stimulus, visual analogue scale score, time to first analgesic requirement, postoperative nausea and vomiting, postoperative opioid consumption, urethral irritation, and incidence of drug-related adverse effects., Results: Total perioperative opioid consumption in the erector spinae plane block group was 355.0 (265.0, 485.0) μg and 240.0 (145.0, 370.0) μg in the intrathecal morphine group (P = 0.09). However, the patients in the erector spinae plane block group had significantly greater postoperative fentanyl consumption (235.0 [120.0, 345.0] μg) compared with those in the intrathecal morphine group (105.0 [30.0, 225.0] μg). There were no statistically significant differences noted for intraoperative opioid consumption, postoperative visual analogue scale score, time to first analgesic request, postoperative nausea and vomiting, and catheter irritation between the two groups., Conclusions: Although no statistically significant difference in intraoperative opioid consumption was seen between the erector spinae plane block and intrathecal morphine groups, postoperative opioid consumption was significantly higher in the erector spinae plane block group than in the intrathecal morphine group in patients undergoing percutaneous nephrolithotomy surgery., (© 2022 The Japanese Urological Association.)

Macrophages are paracrine signalers that regulate tissular responses to injury through interactions with parenchymal cells. Connexin hemichannels have recently been shown to mediate efflux of ATP by macrophages, with resulting cytosolic calcium responses in adjacent cells. Here we report that lung macrophages with deletion of connexin 43 (Mac ΔCx43 ) had decreased ATP efflux into the extracellular space and induced a decreased cytosolic calcium response in co-cultured fibroblasts compared to WT macrophages. Furthermore, Mac ΔCx43 mice had decreased lung fibrosis after bleomycin-induced injury. Interrogating single cell data for human and mouse, we found that P2rx4 was the most highly expressed ATP receptor and calcium channel in lung fibroblasts and that its expression was increased in the setting of fibrosis. Fibroblast-specific deletion of P2rx4 in mice decreased lung fibrosis and collagen expression in lung fibroblasts in the bleomycin model. Taken together, these studies reveal a Cx43-dependent profibrotic effect of lung macrophages and support development of fibroblast P2rx4 as a therapeutic target for lung fibrosis., Competing Interests: The 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 © 2022 Bhattacharyya, Torre, Yadav, Boostanpour, Chen, Tsukui, Sheppard, Muramatsu, Seed, Nishimura, Jung, Tang, Allen and Bhattacharya.)

Simple and efficient methods are a key consideration for small molecule and polymer syntheses. Direct arylation polymerization (DArP) is of increasing interest for preparing conjugated polymers as an effective approach compared to conventional cross-coupling polymerizations. As DArP sees broader utilization, advancements are needed to access materials with improved properties and different monomer structures and to improve the scalability of conjugated polymer synthesis. Presented herein are considerations for developing new methods of conjugated polymer synthesis from small molecule transformations, exploring how DArP has successfully used this approach, and presenting how emerging polymerization methodologies are developing similarly. While it is common to adapt small molecule methods to polymerizations, we demonstrate the ways in which information gained from studying polymerizations can inform and inspire greater advancements in small molecule transformations. This circular approach to organic synthetic method development underlines the value of collaboration between small molecule and polymer-based synthetic research groups.

Buprenorphine (BUP) is a potent opioid analgesic that is widely used for severe pain management and opioid replacement therapy. The oral bioavailability of BUP, however, is significantly limited by first-pass metabolism. Previous studies have shown that triglyceride (TG) mimetic prodrugs of the steroid hormone testosterone circumvent first-pass metabolism by directing drug transport through the intestinal lymphatics, bypassing the liver. The current study expanded this prodrug strategy to BUP. Here different self-immolative (SI) linkers were evaluated to conjugate BUP to the 2 position of the TG backbone via the phenol group on BUP. The SI linkers were designed to promote drug release in plasma. Lipolysis of the prodrug in the intestinal tract was examined via incubation with simulated intestinal fluid (SIF), and potential for parent drug liberation in the systemic circulation was evaluated via incubation in rat plasma. Lymphatic transport and bioavailability studies were subsequently conducted in mesenteric lymph duct or carotid artery-cannulated rats, respectively. TG prodrug derivatives were efficiently transported into the lymphatics (up to 45% of the dose in anaesthetised rats, vs. less than 0.1% for BUP). Incorporation of the SI linkers facilitated BUP release from the prodrugs in the plasma and in concert with high lymphatic transport led to a marked enhancement in oral bioavailability (up to 22-fold) compared to BUP alone. These data suggest the potential to develop an orally bioavailable BUP product which may have advantages with respect to patient preference when compared to current sublingual, transdermal patch or parenteral formulations., Competing Interests: TQ, LH, SH, NT, JS, and CP are inventors of a lymph-directing glyceride prodrug technology that has been licensed to PureTech Health, Boston. TQ and JS are currently employed by PureTech Health. 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 © 2022 Quach, Hu, Han, Lim, Senyschyn, Yadav, Trevaksis, Simpson and Porter.)

Liquid-liquid phase separation (LLPS) is a crucial phenomenon for the formation of functional membraneless organelles. However, LLPS is also responsible for protein aggregation in various neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease (PD). Recently, several reports, including ours, have shown that α-synuclein (α-Syn) undergoes LLPS and a subsequent liquid-to-solid phase transition, which leads to amyloid fibril formation. However, how the environmental (and experimental) parameters modulate the α-Syn LLPS remains elusive. Here, we show that in vitro α-Syn LLPS is strongly dependent on the presence of salts, which allows charge neutralization at both terminal segments of protein and therefore promotes hydrophobic interactions supportive for LLPS. Using various purification methods and experimental conditions, we showed, depending upon conditions, α-Syn undergoes either spontaneous (instantaneous) or delayed LLPS. Furthermore, we delineate that the kinetics of liquid droplet formation (i.e., the critical concentration and critical time) is relative and can be modulated by the salt/counterion concentration, pH, presence of surface, PD-associated multivalent cations, and N-terminal acetylation, which are all known to regulate α-Syn aggregation in vitro. Together, our observations suggest that α-Syn LLPS and subsequent liquid-to-solid phase transition could be pathological, which can be triggered only under disease-associated conditions (high critical concentration and/or conditions promoting α-Syn self-assembly). This study will significantly improve our understanding of the molecular mechanisms of α-Syn LLPS and the liquid-to-solid transition.

Bael ( Aegle marmelos Correa), an important fruit of Indian subtropics, traditionally utilized in the preparation of preserve, candy, squash, RTS, etc. has immense therapeutic potential. An attempt was made to develop a bael based low alcoholic sweet fermented beverage ( may be called as bael cider), anti-oxidant fortified with 0.25 per cent bael leaf or 10 per cent Indian goose berry ( Emblica officinalis Gaertn.) juice in separate batches. Unfortified bael pulp based drink was kept as control. The ameliorated pulp was fermented at 30 ± 2ºC using Saccharomyces cerevisiae. The gooseberry blended bael fermented beverage had higher anti-oxidant content in the form of phenolics (323 mg/100 ml) than leaf extract added fermented beverage (265 mg/100 ml) and control (266 mg/100 ml). Sensory evaluation of product revealed that gooseberry blended fermented beverage scored higher (8.2/10) than bael leaf blended fermented beverage (7.9/10) and control (7.0/10). Twelve months maturation study of beverage revealed increase in reducing sugars and decrease in phenolic content in all the treatments. Bael fermented beverage with gooseberry blend retained highest phenolic content (257 mg/100 ml) and sensory score 7.8/10. The study inferred that an acceptable quality fermented drink could be prepared from bael-gooseberry blend, which could be stored for one year with higher antioxidant value and minimum deterioration in the quality., Competing Interests: Conflicts of interestThe authors declare no real or apparent conflicting or competing interest., (© Association of Food Scientists & Technologists (India) 2021.)

Septic arthritis is a chronic inflammatory disorder caused by Staphylococcus aureus invasion of host synovium, which often progresses to impairment of joint functions. Although it is known that disease progression is intricately dependent on dysregulated inflammation of the knee joint, identification of molecular events mediating such imbalance during S. aureus -induced septic arthritis still requires detailed investigation. In this article, we report that Aurora kinase A (AURKA) responsive WNT signaling activates S. aureus infection-triggered septic arthritis, which results in inflammation of the synovium. In this context, treatment with adapalene, a synthetic retinoid derivative, in a mouse model for septic arthritis shows significant reduction of proinflammatory mediators with a simultaneous decrease in bacterial burden and prevents cartilage loss. Mechanistically, adapalene treatment inhibits WNT signaling with concomitant activation of HIPPO signaling, generating alternatively activated macrophages. Collectively, we establish adapalene as a promising strategy to suppress S. aureus -induced irreversible joint damage., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Introduction: Around 9% of India's children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants <5 months. In addition, children with developmental delay, intellectual disabilities, late detected genetic disorders or autism spectrum disorder show abnormal general movements (GMs) during infancy. General Movement Assessment in Neonates for Early Identification and Intervention, Social Support and Health Awareness (G.A.N.E.S.H.) aims to (1) provide evidence as to whether community health workers can support the identification of infants at high-risk for neurological and developmental disorders and disabilities, (2) monitor further development in those infants and (3) initiate early and targeted intervention procedures., Methods: This 3-year observational cohort study will comprise at least 2000 infants born across four districts of Uttar Pradesh, India. Community health workers, certified for GMA, video record and assess the infants' GMs twice, that is, within 2 months after birth and at 3-5 months. In case of abnormal GMs and/or reduced MOSs, infants are further examined by a paediatrician and a neurologist. If necessary, early intervention strategies (treatment as usual) are introduced. After paediatric and neurodevelopmental assessments at 12-24 months, outcomes are categorised as normal or neurological/developmental disorders. Research objective (1): to relate the GMA to the outcome at 12-24 months. Research objective (2): to investigate the impact of predefined exposures. Research objective (3): to evaluate the interscorer agreement of GMA., Ethics and Dissemination: G.A.N.E.S.H. received ethics approval from the Indian Government Chief Medical Officers of Varanasi and Mirzapur and from the Ramakrishna Mission Home of Service in Varanasi. GMA is a worldwide used diagnostic tool, approved by the Ethics Committee of the Medical University of Graz, Austria (27-388 ex 14/15). Apart from peer-reviewed publications, we are planning to deploy G.A.N.E.S.H. in other vulnerable settings., Competing Interests: Competing interests: The GM Trust supports G.A.N.E.S.H. CE is a GM Trust tutor for GMA, and PBM is president of the GM Trust (honorary function), both of whom have contributed to G.A.N.E.S.H. on an honorary basis., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Apicomplexan parasites, through their motor machinery, produce the required propulsive force critical for host cell-entry. The conserved components of this so-called glideosome machinery are myosin A and myosin A Tail Interacting Protein (MTIP). MTIP tethers myosin A to the inner membrane complex of the parasite through 20 amino acid-long C-terminal end of myosin A that makes direct contacts with MTIP, allowing the invasion of Plasmodium falciparum in erythrocytes. Here, we discovered through screening a peptide library, a de-novo peptide ZA1 that binds the myosin A tail domain. We demonstrated that ZA1 bound strongly to myosin A tail and was able to disrupt the native myosin A tail MTIP complex both in vitro and in vivo. We then showed that a shortened peptide derived from ZA1, named ZA1S, was able to bind myosin A and block parasite invasion. Overall, our study identified a novel anti-malarial peptide that could be used in combination with other antimalarials for blocking the invasion of Plasmodium falciparum .

Objectives: To study aetiology and management of complicated genital fistulae and to evaluate the outcome of the treatment., Methods: This observational study enrolled patients with complicated genital fistulae from September 2008 to August 2018 at Sant Parmanand Hospital, Delhi. Patients underwent a reparative surgery or ureteric stenting after a detailed preoperative workup. Patients were followed up for the assessment of outcomes., Results: A total of 16 patients were recruited: Ten (62.5%) patients had fistulae secondary to gynaecological surgeries (seven laparoscopic and three abdominal hysterectomies) and six (37.5%) patients had obstetric fistulae. At a mean follow-up of 5.8 years among obstetric fistulae and 7.3 years among post-operative fistulae, 100% success rate was maintained with the first attempt of reparative surgery or ureteric stenting. There were no major complications. Two patients had recurrent urinary tract infections, and one patient had transient urinary incontinence for 4 weeks., Conclusion: The study demonstrates that complicated genital fistulae occur more commonly secondary to gynaecological surgeries as compared to obstetric complications in a contemporary cohort from a metropolitan city. A 100% success rate of reparative surgery could be achieved with a transperitoneal approach. Good outcome in ureteric fistulae can be achieved with conservative approach, after proper case selection., Competing Interests: Conflict of interestAll the co-authors declare that there is no conflict of interest., (© Federation of Obstetric & Gynecological Societies of India 2019.)

In this article, we report the effect of electropolymerization conditions such as solvent and supporting electrolyte on the redox, optoelectronic and electrochromic properties of PEDOS. Monomer EDOS was synthesized by new and simple route and its electropolymerization was investigated by employing six different combinations of solvent-electrolyte namely TBAClO 4 /MeCN, TBAPF 6 /MeCN, TBABF 4 /MeCN, TBAClO 4 /PC, TBAPF 6 /PC and TBABF 4 /PC. Further, the electrochemical, spectroelectrochemistry, morphology and electrochromic properties of resultant PEDOS films were systematically studied. A pronounced effect of both solvent and supporting electrolyte on the electropolymerization, redox, optoelectronic and electrochromic properties on PEDOS film is noted. Among all solvent-electrolyte systems, MeCN and TBAClO 4 were found to be the most suitable medium for electropolymerization of EDOS. Further, PEDOS films prepared in PC showed red shifted absorption maxima, narrow absorption peaks in UV-vis-NIR spectra, slightly more smooth morphologies, and high optical contrasts ratio and coloration efficiency in comparison to MeCN. PEDOS films prepared in TBABF 4 /PC exhibited longer λ max (670 nm), smooth morphology, and the highest optical contrasts ratio (44.6%) and coloration efficiency (141.8 cm 2 C -1 ) compared to the other solvent-electrolyte medium., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Esophageal cancer is the eighth most common occurring cancer type worldwide and 6th most common among the cancer related deaths of which the most common type is squamous cell carcinoma which comprise about 90% of esophageal cancer cases. The standard of care for esophageal cancer is neoadjuvant concurrent chemotherapy and radiation (NACRT) followed by surgery however the prognosis remains dismal with 5 year survival a meager 10-15%. The treatment modalities for esophageal cancer is associated with both long term and short term toxicities. Curcumin has been explored as a therapeutic modality as a chemo adjuvant in different cancers due to its low toxicity profile and potent anticancer effect however despite lot of promising preclinical data it has not progressed from bench side to bed side. The primary reason that has obstructed its application in clinic has been its low bioavailability which was seen in different clinical trials but there has been tremendous progress in developing formulations of curcumin which have significantly increased its bioavailability and are being tested in clinical trials. Esophageal cancer is associated with inflammation that’s why curcumin being a natural antioxidant offer a potential avenue to reduce toxicity of current therapeutic modalities in a chemo adjuvant setting while simultaneously targeting different pro oncogenic pathways. The present review tries to cover in depth different aspects of curcumin application in treatment of esophageal cancer and progress of this potent anticancer agent in its treatment and prevention., (Creative Commons Attribution License)

Bioisosterism is a useful strategy in rational drug design to improve pharmacodynamic and pharmacokinetic properties of lead compounds. Imidazolidinones have been reported as potent kinase inhibitors and antileishmanial agents. In this study, bioisosteres of imidazolidinones (compounds 1-3) were evaluated for their antileishmanial properties. The modified imidazolidinones exhibited potent antileishmanial activity against extracellular as well as intracellular Leishmania donovani parasites in nanomolar concentrations. The selectivity index of these compounds on host cells was found to be more than 1000, emphasizing their specificity toward the parasite. Using SwissTargetPrediction software, we assessed the potential targets of these compounds and found MAPK as the most probable target. To in vitro validate, we developed a novel in vitro kinase assay that mimics the in vivo nature of the functional kinome. Compounds 1-3 displayed specific inhibition of parasite kinase activity accompanied by an increase in intracellular sodium levels in the parasites. This might be the effect of kinase inhibition that regulates sodium homeostasis through Na-ATPases. Finally, the compound-treated parasites underwent apoptosis-like death. This study represents bioisoterism as a novel approach for drug design to establish the structure-activity relationship, which in turn helps to improve the therapeutic activity of lead compounds., (© 2019 Deutsche Pharmazeutische Gesellschaft.)

Three random copolymers PE- co -M1 , PE- co -M2 , and PE- co -M3 were obtained by electrochemical polymerization of donor-acceptor-donor monomers M1 , M2 , and M3 with 3,4-ethylenedioxythiophene moiety, respectively, using a 1:1 molar ratio of the corresponding monomers, to find new properties and a more effective way to control the optoelectronic properties in conjugated system. For comparison purpose, polymers P1 , P2 , and P3 were prepared from the corresponding monomer units M1 - M3 , respectively, by electrochemical polymerization. We also present efficient synthesis, characterization, and comparative density functional theory (DFT) calculations of the monomers M1 - M3 and polymers P1 - P3 . Cyclic voltammetry, spectroelectrochemistry, and electrochromic properties of all of the polymers P1 - P3 and copolymers PE- co -M1 , PE- co -M2 , and PE- co -M3 were carried out and a throughout comparison was made. We have shown that electrochemical copolymerization is a powerful strategy to tune the highest occupied molecular orbital energy level, band gap, and color of the copolymer. Thus, this finding clearly indicates that the copolymers show significantly different optoelectronic properties compared to their constituent polymers., Competing Interests: The authors declare no competing financial interest.

Lipid-based palmitoylation is a post-translation modification (PTM) which acts as a biological rheostat in life cycle progression of a deadly human malaria parasite, Plasmodium falciparum . P. falciparum palmitoylation is catalyzed by 12 putative palmitoyl acyl-transferase enzymes containing the conserved DHHC-CRD (DHHC motif within a cysteine-rich domain) which can serve as a druggable target. However, the paucity of high-throughput assays has impeded the design of drugs targeting palmitoylation. We have developed a novel strategy which involves engineering of Escherichia coli , a PTM-null system, to enforce ectopic expression of palmitoyl acyl-transferase in order to study Plasmodium -specific palmitoylation and screening of inhibitors. In this study, we have developed three synthetic E. coli strains expressing Plasmodium -specific DHHC proteins (PfDHHC7/8/9). These cells were used for validating acyl-transferase activity via acyl-biotin exchange (ABE) and clickable chemistry methods. E. coli proteome was found to be palmitoylated in PfDHHC-expressing clones, suggesting that plasmodium DHHC can catalyze palmitoylation of E. coli proteins. Upon treatment with generic inhibitor 2-bromopalmitate (2-BMP), a predominant reduction in palmitic acid incorporation is detected. Overall, these findings suggest that synthetic E. coli strains expressing PfDHHCs can enforce global palmitoylation in the E. coli proteome. Interestingly, this finding was corroborated by our in silico palmitoylome profiling, which revealed that out of the total E. coli proteome, 108 proteins were predicted to be palmitoylated as represented by the presence of three cysteine consensus motifs (cluster type I, II, III). In summary, our study reports a proof of concept for screening of chemotherapeutics targeting the palmitoylation machinery using a high-throughput screening platform.

Tissue repair is a complex process that necessitates an interplay of cellular processes, now known to be dictated by epigenetics. Intriguingly, macrophages are testimony to a large repertoire of evolving functions in this process. We identified a role for BMP signaling in regulating macrophage responses to Candida albicans infection during wound repair in a murine model. In this study, the RNA binding protein, AU-rich element-binding factor 1, was posttranslationally destabilized to bring about ubiquitin ligase, NEDD4-directed activation of BMP signaling. Concomitantly, PI3K/PKCδ mobilized the rapid phosphorylation of BMP-responsive Smad1/5/8. Activated BMP pathway orchestrated the elevated recruitment of EZH2 at promoters of genes assisting timely wound closure. In vivo, the repressive H3K27 trimethylation was observed to persist, accompanied by a robust upregulation of BMP pathway upon infection with C. albicans, culminating in delayed wound healing. Altogether, we uncovered the signaling networks coordinated by fungal colonies that are now increasingly associated with the infected wound microbiome, resulting in altered wound fate., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Palmitoylation has been recently identified as an important post-translational rheostat for controlling protein function in eukaryotes. However, the molecular machinery underlying palmitoylation remains unclear in the neglected tropical parasite, Leishmania donovani . Herein, we have identified a catalog of 20 novel palmitoyl acyltransferases (PATs) and characterized the promastigote-specific PAT (LdPAT4) containing the canonical Asp-His-His-Cys (DHHC) domain. Immunofluorescence analysis using in-house generated LdPAT4-specific antibody demonstrated distinct expression of LdPAT4 in the flagellar pocket of promastigotes. Using metabolic labeling-coupled click chemistry method, the functionality of this recombinant enzyme could be authenticated in E. coli strain expressing LdPAT4-DHHC domain. This was evident by the cellular uptake of palmitic acid analogs, which could be successfully inhibited by 2-BMP, a PAT-specific inhibitor. Using CSS-Palm based in-silico proteomic analysis, we could predict up to 23 palmitoylated sites per protein in the promastigotes, and further identify distinctive palmitoylated protein clusters involved in microtubule assembly, flagella motility and vesicular trafficking. To highlight, proteins such as Flagellar Member proteins (FLAM1, FLAM5), Intraflagellar Transport proteins (IFT88), and flagellar motor assembly proteins including the Dynein family were found to be enriched. Furthermore, analysis of global palmitoylation in promastigotes using Acyl-biotin exchange purification identified a set of S-palmitoylated proteins overlapping with the in-silico proteomics data. The attenuation of palmitoylation using 2-BMP demonstrated several phenotypic alterations in the promastigotes including distorted morphology, reduced motility (flagellar loss or slow flagellar beating), and inefficient invasion of promastigotes to host macrophages. These analyses confirm the essential role of palmitoylation in promastigotes. In summary, the findings suggest that LdPAT4 acts as a functional acyltransferase that can regulate palmitoylation of proteins involved in parasite motility and invasion, thus, can serve as a potential target for designing chemotherapeutics in Visceral Leishmaniasis.

Competing Interests: There are no conflicts of interest.

Therapeutic proteins can facilitate the targeting and treatment of lymphatic diseases (such as cancer metastases, infections and inflammatory diseases) since they are cleared via the lymphatics following interstitial (SC or IM) administration. However, therapeutic proteins are often administered intravenously (IV). Recently therapeutic proteins have been found to access the thoracic lymph in surprisingly high quantities after IV administration. The aim of this study was to determine, for the first time, the major sites of thoracic lymph access of therapeutic proteins, and the protein properties that enhance lymph access, after IV administration. In order to achieve this, novel methods were developed or optimized to collect hepatic, mesenteric or thoracic lymph from male SD rats. Four different sized PEGylated or non-PEGylated therapeutic proteins (native interferon α2b (IFN, 19kDa), PEGylated interferon α2b (IFN-PEG12, 31kDa), PEGylated interferon α2a (IFN-PEG40, 60kDa) or trastuzumab (150kDa)) were then administered via short IV infusion, and plasma and lymph concentrations of the proteins determined via ELISA. The recovery of the therapeutic proteins in the thoracic lymph duct, which collects lymph from most of the body, was significantly greater for trastuzumab, IFN-PEG40 and IFN-PEG12 (all >3% dose over 8h) when compared to native IFN (0.9% dose). Conversely, the thoracic lymph/plasma (L/P) concentration ratio and thus efficiency of extravasation and transport through the interstitium to lymph was highest for the smaller proteins IFN and IFN-PEG12 (at 90-100% vs 15-30% for trastuzumab and IFN-PEG40). The lower total recovery of IFN and IFN-PEG12 in thoracic lymph reflected more rapid systemic clearance and thus lower systemic exposure. For all therapeutic proteins, the majority (>80%) of lymph access occurred via the hepatic and mesenteric lymphatics. This lymphatic distribution pattern was supported by quantitative imaging of the lymph node distribution of IV administered Cy5 labelled trastuzumab. Optimizing the properties of IV administered therapeutic proteins represents a viable approach to better target and treat pathological states involving the lymphatics, particularly in the liver and mesentery. This includes cancer metastases, infections and inflammatory diseases. Successful development of the novel technique to collect hepatic lymph will also enable future work to evaluate tissue-specific lymph transport in health and disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this report, we describe the case of a premature infant (36 weeks' postgestational age) who underwent left inguinal hernia repair under general anesthesia without the use of any airway device. Anesthesia was induced and maintained with sevoflurane in oxygen and nitrous oxide. An ultrasound-guided transversus abdominis plane block was performed that provided effective analgesia, obviating the need for opioids in the intraoperative period. The infant's hemodynamics remained stable throughout the surgery. This report also briefly explains the advantages of using a transversus abdominis plane block, compared with neuraxial blockade, for hernia repair surgery.

First-pass hepatic metabolism can significantly limit oral drug bioavailability. Drug transport from the intestine through the lymphatic system, rather than the portal vein, circumvents first-pass metabolism. However, the majority of drugs do not have the requisite physicochemical properties to facilitate lymphatic access. Herein, we describe a prodrug strategy that promotes selective transport through the intestinal lymph vessels and subsequent release of drug in the systemic circulation, thereby enhancing oral bioavailability. Using testosterone (TST) as a model high first-pass drug, glyceride-mimetic prodrugs incorporating self-immolative (SI) spacers, resulted in remarkable increases (up to 90-fold) in TST plasma exposure when compared to the current commercial product testosterone undecanoate (TU). This approach opens new opportunities for the effective development of drugs where oral delivery is limited by first-pass metabolism and provides a new avenue to enhance drug targeting to intestinal lymphoid tissue., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To compare the accuracy of rapid bedside tests for phosphorylated insulin-like growth factor-binding protein 1 (phIGFBP-1) and fetal fibronectin (fFN) to predict preterm delivery among women with threatened preterm labor., Methods: A prospective observational study was conducted among women with a singleton pregnancy of 28-36 weeks, intact membranes, and symptoms suggestive of preterm labor who attended a center in New Delhi, India, between April 1, 2011, and March 31, 2014. Rapid bedside tests were performed at presentation to measure the levels of phIGFBP-1 and fFN in cervicovaginal secretions. All patients were managed as per the standard hospital protocol and followed up until delivery., Results: Data were available for 468 participants. For delivery before 37 weeks, the phIGFBP-1 test exhibited a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81.1%, 97.1%, 95.2% and 87.7%, respectively. The sensitivity, specificity, PPV, and NPV for the fFN test were 19.4%, 99.4%, 97.4%, and 63.2%, respectively. The phIGFBP-1 test displayed higher sensitivity and NPV than did the fFN test for delivery before 34 weeks and within 7 days of testing (P<0.05 for all)., Conclusion: The rapid bedside test for phIGFBP-1 was more reliable in the prediction of preterm delivery than was the equivalent test for fFN., (Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

In neurons, microtubules form a dense array within axons, and the stability and function of this microtubule network is modulated by neurofilaments. Accumulation of neurofilaments has been observed in several forms of neurodegenerative diseases, but the mechanisms how elevated neurofilament levels destabilize axons are unknown so far. Here, we show that increased neurofilament expression in motor nerves of pmn mutant mice, a model of motoneuron disease, causes disturbed microtubule dynamics. The disease is caused by a point mutation in the tubulin-specific chaperone E (Tbce) gene, leading to an exchange of the most C-terminal amino acid tryptophan to glycine. As a consequence, the TBCE protein becomes instable which then results in destabilization of axonal microtubules and defects in axonal transport, in particular in motoneurons. Depletion of neurofilament increases the number and regrowth of microtubules in pmn mutant motoneurons and restores axon elongation. This effect is mediated by interaction of neurofilament with the stathmin complex. Accumulating neurofilaments associate with stathmin in axons of pmn mutant motoneurons. Depletion of neurofilament by Nefl knockout increases Stat3-stathmin interaction and stabilizes the microtubules in pmn mutant motoneurons. Consequently, counteracting enhanced neurofilament expression improves axonal maintenance and prolongs survival of pmn mutant mice. We propose that this mechanism could also be relevant for other neurodegenerative diseases in which neurofilament accumulation and loss of microtubules are prominent features.

Unlike some vertebrates and fishes, humans do not have the capacity for tooth regeneration after the loss of permanent teeth. Although artificial replacement with removable dentures, fixed prosthesis and implants is possible through advances in the field of prosthetic dentistry, it would be ideal to recreate a third set of natural teeth to replace lost dentition. For many years now, researchers in the field of tissue engineering have been trying to bioengineer dental tissues as well as whole teeth. In order to attain a whole tooth through dental engineering, that has the same or nearly same biological, mechanical and physical properties of a natural tooth, it's necessary to deal with all the cells and tissues which are concerned with the formation, maintenance and repair of the tooth. In this article we review the steps involved in odontogenesis or organogenesis of a tooth and progress in the bioengineering of a whole tooth.

We have synthesized two novel fluorescent 3-(4-diethylaminocinnamoyl) coumarins that exhibit fluorescence quenching upon exposure to a nerve agent simulant, diethylchlorophosphate (DCP), providing a basis for rapid and sensitive DCP chemosensing. Furthermore, these coumarin derivatives display two-photon fluorescence upon illumination with near-infrared laser pulses and their two-photon (TP) absorption cross-section was evaluated. The potential for TP bio-imaging of these compounds was investigated by their cellular uptake in HeLa cells by TP confocal microscopy.

Biopolymers provide a plethora of applications in the pharmaceutical and medical applications. A material that can be used for biomedical applications like wound healing, drug delivery and tissue engineering should possess certain properties like biocompatibility, biodegradation to non-toxic products, low antigenicity, high bio-activity, processability to complicated shapes with appropriate porosity, ability to support cell growth and proliferation and appropriate mechanical properties, as well as maintaining mechanical strength. This paper reviews biodegradable biopolymers focusing on their potential in biomedical applications. Biopolymers most commonly used and most abundantly available have been described with focus on the properties relevant to biomedical importance.

Abrin is a potent plant toxin. It is a heterodimeric protein toxin which is obtained from the seeds of Abrus precatorius plant. At cellular level abrin causes protein synthesis inhibition by removing the specific adenine residue (A4324) from the 28s rRNA of the 60S - ribosomal subunit. In the present study we investigated the role of oxidative stress in neurotoxic potential and demyelinating effects of abrin on brain. The mechanism by which abrin induces oxidative damage and toxicity in brain are relatively unknown. Animals were exposed to 0.4 and 1.0 LD50 abrin dose by intraperitoneal route and observed for 1 and 3 day post-toxin exposure. Oxidative stress occurred in brain due to abrin was confirmed in terms of increased reactive oxygen species (ROS), glutathione depletion and increased lipid peroxidation. Significant increase in blood and brain ROS was observed at day 3, 1 LD50. Abrin induced changes in the neurotransmitters (5-hydroxy tryptamine, norepinephrine, dopamine and monoamine oxidase) levels were evaluated by spectroflourometry. Increase in the levels of 5-HT and NE was observed after abrin exposure. MAO activity was found to be decreased in abrin exposed animals compared to control. Significant inhibition in the activity of acetylcholine esterase enzyme in brain and serum was reported for both the doses and time points. Western blot analysis of iNOS expression indicated that abrin treatment resulted in dose and time dependent increase. Furthermore, protein expression of myelin basic protein (MBP) was down regulated in a dose and time dependent manner. Brain histopathology was carried out and cortical brain region showed demyelination after abrin exposure. Results confirmed that abrin poisoning leads to neurodegeneration and neurotoxicity mediated through oxidative stress, AChE inhibition, lipid peroxidation and decrease in MBP levels., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease affecting lower motor neurons. SMA is caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, which result in reduced levels of functional SMN protein. Biochemical studies have linked the ubiquitously expressed SMN protein to the assembly of pre-mRNA processing U snRNPs, raising the possibility that aberrant splicing is a major defect in SMA. Accordingly, several transcripts affected upon SMN deficiency have been reported. A second function for SMN in axonal mRNA transport has also been proposed that may likewise contribute to the SMA phenotype. The underlying etiology of SMA, however, is still not fully understood. Here, we have used a combination of genomics and live Ca(2+) imaging to investigate the consequences of SMN deficiency in a zebrafish model of SMA. In a transcriptome analyses of SMN-deficient zebrafish, we identified neurexin2a (nrxn2a) as strongly down-regulated and displaying changes in alternative splicing patterns. Importantly, the knock-down of two distinct nrxn2a isoforms phenocopies SMN-deficient fish and results in a significant reduction of motor axon excitability. Interestingly, we observed altered expression and splicing of Nrxn2 also in motor neurons from the Smn(-/-);SMN2(+/+) mouse model of SMA, suggesting conservation of nrxn2 regulation by SMN in mammals. We propose that SMN deficiency affects splicing and abundance of nrxn2a. This may explain the pre-synaptic defects at neuromuscular endplates in SMA pathophysiology.

Chromones (1-benzopyran-4-ones) are natural occurring compounds present in representative amounts in a normal human diet and are associated with interesting physiological activities such as antiinflammatory, antidiabetic, antitumor, anticancer etc. These biological activities are thought to be related to the antioxidant properties of chromones i.e. to neutralize active oxygen and to cut off free radicals processes that can delay or inhibit cell impairment which leads to various diseases. In this review, we have summarized the literature reports published in about 70 research articles during the period January 2004 to March 2014 on more than 400 naturally as well as the synthetically derived chromone derivatives having antioxidant potential. The literature reports suggest that the double bond, a carbonyl group of chromone and 3´,4´-dihydroxy group (catechol) in ring B along with the C-3 and C-5 hydroxyl groups are important for radical scavenging activity. In turn, a decrease in the radical scavenging potential has been observed upon methylation / glycosylation of the hydroxyl groups on chromone nucleus.