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Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; <1 g, 10-500 Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in Chinese Hamster Ovary (CHO)-adherent cells (+79% in 96 hr) using a particular set of LIV parameters (0.2 g, 500 Hz, 3 × 30 min/d, 2 hr refractory period), yet this same mechanical input suppressed proliferation in CHO-suspension cells (-13%). Another set of LIV parameters (30 Hz, 0.7 g, 2 × 60 min/d, 2 hr refractory period) however, were able to increase the proliferation of CHO-suspension cells by 210% and T-cells by 20.3%. Importantly, we also reported that T-cell response to LIV was in-part dependent upon AKT phosphorylation, as inhibiting AKT phosphorylation reduced the proliferative effect of LIV by over 60%, suggesting that suspension cells utilize mechanism(s) similar to adherent cells to sense specific LIV signals. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (>90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, it's highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial biocentric production challenges., Competing Interests: Declaration of competing interest CTR has several issued and pending patents on the use of low intensity vibration and extremely low magnitude mechanical signals to promote cell proliferation and differentiation, both in vitro and in vivo. He is also the founder of Lahara Bio and Marodyne Medical. No other authors have any conflicts to declare.

Background: Detecting anthracyclines-induced cardiotoxicity before the onset of left ventricular dysfunction could enable the timely initiation of cardioprotective measures. 2D-Echocardiography (ECHO) with global longitudinal strain (GLS) and cardiac biomarkers are valuable for the early prediction of cardiotoxicity., Objectives: We aimed to evaluate the predictive utility of 2D-ECHO-GLS and cardiac biomarkers exclusively in patients with lymphoma treated with a doxorubicin-based regimen., Methods: The study included lymphoma patients ≥14 years of age of either sex who were planned for a doxorubicin-based regimen. All eligible patients underwent 2D-ECHO-GLS and cardiac biomarkers (troponin T and pro-brain natriuretic peptide) measurements at the baseline (V1), after 3 rd chemotherapy cycle (V2), and after treatment completion (V3). Incidence, risk factors, and early predictors for cardiotoxicity were assessed using SPSS software version 25. The study was registered with CTRI (CTRI/2021/07/034518)., Results: 40 patients (median age, 42 years) had evaluations available at all 3 time points. Three out of 40 (7.5%) patients developed cardiotoxicity at V3. Patients with cardiotoxicity had a significantly higher mean age (P = .045) and a greater incidence of hypertension (P = .012) than those without cardiotoxicity. At V2, the mean GLS threshold (-18.1%) and Δ GLS threshold ≥15% from baseline were significant early predictors of subsequent cardiotoxicity. Despite an exponential rise from V1 to V3, the cardiac biomarkers failed to predict cardiotoxicity., Conclusions: Patients with lymphoma treated with doxorubicin-based regimens have a significant risk of developing cardiac dysfunction. A greater than 15% fall in GLS from baseline after 3 rd chemotherapy cycle could predict subsequent cardiotoxicity., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Curcumin, a compound in turmeric, shows promise for its anti-cancer properties. In this study, we successfully synthesised curcumin-reduced and capped gold nanoparticles. Most evaluations have been limited to in-vitro studies for these nanoparticles; our study takes a step further by highlighting the in-vivo assessment of these curcumin-reduced and capped gold nanoparticles (GNPCs) using non-invasive imaging (SPECT and optical) and possible therapeutic potential. The GNPCs showed an average hydrodynamic diameter of 58 nm and a PDI of 0.336. The synthesised and fully characterised GNPCs showed ex-vivo hemolysis value of ≤ 1.74 % and serum stability of ≥ 95 % over 24 h. Using in-vivo non-invasive (SPECT and optical Imaging), prolonged circulation and enhanced bioavailability of GNPCs were seen. The biodistribution studies after radiolabelling GNPCs with 99 m Tc complemented the optical imaging. The SPECT images showed higher uptake of the GNPCs at the tumour site, viz the contralateral muscle and the native Curcumin, resulting in a high target-to-non-target ratio that differentiated the tumour sufficiently and enhanced the diagnostics. Other organs also accumulate radiolabeled GNPCs in systemic circulation; bio dosimetry is performed. It was found that the dose received by the different organs was safe for use, and the in-vivo toxicity studies in rats indicated negligible toxicity over 30 days. The tumour growth was also reduced in mice models treated with GNPCs compared to the control. These significant findings demonstrate that GNPC shows synergistic activity in vivo, indicating its ability as a green diagnostic probe that has the potential for therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Recent advancements in wound care have led to the development of interactive wound dressings utilizing nanotechnology, aimed at enhancing healing and combating bacterial infections while adhering to established protocols. Our novel wound dressings consist of N,N,N-trimethyl chitosan capped gold‑silver nanoparticles (Au-Ag-TMC-NPs), with a mean size of 108.3 ± 8.4 nm and a zeta potential of +54.4 ± 1.8 mV. These optimized nanoparticles exhibit potent antibacterial and antifungal properties, with minimum inhibitory concentrations ranging from 0.390 μg ml -1 to 3.125 μg ml -1 and also exhibited promising zones of inhibition against multi-drug resistant strains of S. aureus, E. coli, P. aeruginosa, and C. albicans. Microbial transmission electron microscopy reveals substantial damage to cell walls and DNA condensation post-treatment. Furthermore, the nanoparticles demonstrate remarkable inhibition of microbial efflux pumps and are non-hemolytic in human blood. Incorporated into polyvinyl alcohol/chitosan nanofibers, they form Au-Ag-TMC-NPs-NFs with diameters of 100-350 nm, facilitating efficient antimicrobial wound dressing. In vivo studies on MDR microbial-infected wounds in mice showed 99.34 % wound healing rate within 12 days, corroborated by analyses of wound marker protein expression levels and advanced imaging techniques such as ultrasound/photoacoustic imaging, providing real-time visualization and blood flow assessment for a comprehensive understanding of the dynamic wound healing processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Under the global climate change scenario, ever-increasing ocean temperatures and elevated carbon dioxide (CO 2 ) concentration levels in the ocean and atmosphere significantly affect ocean biogeochemistry. The spatiotemporal distribution of chlorophyll and partial pressure of CO 2 (pCO 2 ) over the Indian Ocean (IO) are investigated using satellite, in-situ, and simulations from eleven Coupled Model Inter-comparison Project phase 6 models. All the models show negative bias near the Somali region over the Arabian Sea (AS) during the southwest monsoon season. The CESMs and CanESM5 models show relatively less bias over the tropical IO except for the AS in all seasons compared to other models. The annual cycle of pCO 2 shows a bimodal characteristic, with the first peak in May and the other in October over the northern IO, which the CanESM5, IPSL, and MPIs models reasonably well capture. All the models produce the phase of the annual cycle of pCO 2 reasonably well for the southern IO. The pCO 2 distribution and its trend decomposition are estimated using the multimodel mean from the CanESM5, IPSL-CM6A-LR, and MPIs models, suggesting that the increase in dissolved inorganic carbon is the dominant factor that contributes to about 70 % of the rise in the total pCO 2 trend, and the total alkalinity and sea surface temperature have a secondary role. Region-wise analysis manifests that the southern IO and AS exhibit maximum susceptibility to the long-term variations in the pCO 2 trend caused by the changes in dissolved inorganic carbon levels in the ocean. The study discusses substantive factors leading to the variability in the biogeochemical properties of the IO as simulated by these models and, thus, the possibilities for future improvements., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this report, we present our studies on mRNA, which was modified by introducing various halogen substituents at the C(5) position of the pyrimidine base. Specifically, we synthesized C(5)-halogenated (F, Cl, Br, I) pyrimidine ribonucleoside triphosphates and incorporated them into mRNA during in-vitro transcription. The efficiency of the in-vitro transcription reaction of halogenated pyrimidine was observed to decrease as the size of the halogen substituent increased and the electronegativity thereof decreased (F > Cl > Br) except for iodine. Interestingly, we found that, among the C(5)-halogenated pyrimidine ribonucleotides, mRNA incorporating C(5)-halogenated cytidine (5-F rCTP and 5-Cl rCTP) exhibited more prominent protein expression than mRNA modified with C(5)-halogenated uridine and unmodified mRNA. In particular, in the case of mRNA to which fluorine (5-F rCTP) and chlorine (5-Cl rCTP) were introduced, the protein was dramatically expressed about 4 to 5 times more efficiently than the unmodified mRNA, which was similar to pseudouridine (ψ). More interestingly, when pseudouridine(ψ) and fluorocytidine nucleotides (5-F rCTP), were simultaneously introduced into mRNA for dual incorporation, the protein expression efficiency dramatically increased as much as tenfold. The efficiency of cap-dependent protein expression is much higher than the IRES-dependent (internal ribosome entry site) expression with mRNA incorporating C(5)-halogenated pyrimidine ribonucleotide. We expect these results to contribute meaningfully to the development of therapeutics based on modified mRNA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Non-gestational ovarian choriocarcinoma (NGOC) is a rare phenomenon seldom reported in the literature. Patients often present with abdominopelvic pain, and sometimes a palpable adnexal mass. Surgical excision is paramount in treating this malignancy; however, fertility-preserving care is a debated topic among gynecologic oncologists. Most patients reported in the literature are nulliparous women of child-bearing age. It is important to consider fertility preservation whilst balancing oncologic outcomes. We present a case of an 18-year-old nulliparous female with stage IIB NGOC that had disease progression in the lungs and pelvis shortly after undergoing fertility-preserving surgery. She required emergent completion surgery and received etoposide (E), methotrexate (M), actinomycin-D (A), cyclophosphamide (C) and vincristine (O) (EMA-CO) with complete response. She remains disease-free after 21-months., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Diabetes and heart disease are 2 prevalent and interconnected conditions with a significant global burden. Understanding the relationship between diabetes and heart disease is crucial for effective management and prevention strategies. This article provides an overview of the 2 conditions, highlighting their types, risk factors, and global prevalence. Recent research findings establish a strong correlation between diabetes and various aspects of cardiovascular health, including coronary artery disease, heart failure, and stroke. Mechanisms such as insulin resistance, inflammation, and oxidative stress contribute to the interplay between diabetes and heart disease. The implications for clinical practice underscore the importance of early detection, risk assessment, and comprehensive management of both conditions. Lifestyle modifications, such as diet, exercise, and weight management, are essential interventions. Pharmacological interventions, including antidiabetic drugs and cardiovascular medications, play a crucial role in treatment. Managing diabetes and heart disease simultaneously poses challenges that require interdisciplinary collaboration among endocrinologists, cardiologists, and primary care physicians. Ongoing research explores personalized medicine and targeted therapies as potential future directions. Continued research and awareness are paramount to mitigate the impact of the diabetes-heart disease connection and improve patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Rheumatoid arthritis (RA) related autoimmunity is developed at mucosal sites due to the interplay between genetic risk factors and environmental triggers. The pre-RA phase that leads to anti-citrullinated protein antibodies, rheumatoid factor, and other autoantibodies spread in the systemic circulation may not affect articular tissue for years until a mysterious second hit triggers the localization of RA-related autoimmunity in joints. Several players in the joint microenvironment mediate the synovial innate and adaptive immunological processes, eventually leading to clinical synovitis. There still exists a gap in the early phase of RA pathogenesis, i.e., the progression of diseases from the systemic circulation to joints. The lack of better understanding of these events results in the inability to answer questions about why only after a certain point of time the disease appears in joints and why in some cases, it simply remains latent and doesn't affect joints at all. In the current review, we focused on the immunomodulatory and regenerative role of mesenchymal stem cells and associated exosomes in RA pathology. We also highlighted the age-related dysregulations in activities of mesenchymal stem cells and how that might trigger homing of systemic autoimmunity to joints., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cellular functions are regulated by signal transduction pathway networks consisting of protein-modifying enzymes that control the activity of many downstream proteins. Protein kinases and phosphatases regulate gene expression by reversible phosphorylation of transcriptional factors, which are their direct substrates. Casein kinase II (CK2) is a serine/threonine kinase that phosphorylates a large number of proteins that have critical roles in cellular proliferation, metabolism and survival. Altered function of CK2 has been associated with malignant transformation, immunological disorders and other types of diseases. Protein phosphatase 1 (PP1) is a serine/threonine phosphatase, which regulates the phosphorylation status of many proteins that are essential for cellular functions. IKAROS is a DNA-binding protein, which functions as a regulator of gene transcription in hematopoietic cells. CK2 directly phosphorylates IKAROS at multiple phosphosites which determines IKAROS activity as a regulator of gene expression. PP1 binds to IKAROS via the PP1-consensus recognition site and dephosphorylates serine/threonine residues that are phosphorylated by CK2. Thus, the interplay between CK2 and PP1 signaling pathways have opposing effects on the phosphorylation status of their mutual substrate - IKAROS. This review summarizes the effects of CK2 and PP1 on IKAROS role in regulation of gene expression and its function as a tumor suppressor in leukemia., Competing Interests: Declaration of competing interest The authors report no conflicts of interest related to the information, materials, or methods reported in this manuscript. The authors report no competeting conflicts of interest with the content of this manuscript., (Copyright © 2022. Published by Elsevier Ltd.)

The high prevalence of neurodegenerative diseases has become a major public health challenge and is associated with a tremendous burden on individuals, society and federal governments worldwide. Protein misfolding and aggregation are the major pathological hallmarks of several neurodegenerative disorders. The cells have evolved several regulatory mechanisms to deal with aberrant protein folding, namely the classical ubiquitin pathway, where ubiquitination of protein aggregates marks their degradation via lysosome and the novel autophagy or mitophagy pathways. Autophagy is a catabolic process in eukaryotic cells that allows the lysosome to recycle the cell's own contents, such as organelles and proteins, known as autophagic cargo. Their most significant role is to keep cells alive in distressed situations. Mitophagy is also crucial for reducing abnormal protein aggregation and increasing organelle clearance and partly accounts for maintaining cellular homeostasis. Furthermore, substantial data indicate that any disruption in these homeostatic mechanisms leads to the emergence of several age-associated metabolic and neurodegenerative diseases. So, targeting autophagy and mitophagy might be a potential therapeutic strategy for a variety of health conditions., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

•Somatic neoplasms in Mature Cystic Teratoma are uncommon; Ganglioneuroblastoma is rare, this is 2nd reported case.•Due to rarity, it can pose a diagnostic challenge for Pathologists, and management and staging conundrum for Gynecologists.•Morphological differentials include immature teratoma, glial neoplasms arising in teratoma, and carcinoid., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Introduction: The presence of 2 or more high-risk cytogenetic abnormalities on FISH characterizes patients as Double/Triple Hit Myeloma (DH/THM). This entity has poorer outcomes, though data from the real-world setting is scarce., Patients and Methods: We retrospectively analyzed all MM patients presenting to our hospital over 3 years to study the clinical characteristics and outcomes with DH/THM., Results: Fifty-five (19.2%) of 285 newly-diagnosed MM patients had DH/THM. The most common cytogenetic abnormality was increased copies of chromosome 1q (53 patients, 96.4%)- 22 patients had 3 copies, and 31 patients had 4 or more copies. The most common cytogenetic combination was IgH-FGFR3 translocation, increasing 1q copy number (28 patients; 50.9%). The disease was characterized by aggressive presentation, with 9 patients (16.4%) dying in the first month after diagnosis, and 7 patients (12.7%) dying in the second month. Only 22 patients (40%) achieved a VGPR or better with therapy. The Median EFS and OS for the cohort were 8 months and thirteen months, respectively. On multi-variate analysis, renal failure and plasma cell leukemia were associated with increased mortality risk, while achievement of VGPR or better was associated with better survival., Conclusion: Our findings suggest that multiple myeloma patients with double/triple hit cytogenetics on FISH have aggressive presentations, high early mortality, and poor outcomes. These patients may benefit from more aggressive regimens and better supportive care., (Copyright © 2022. Published by Elsevier Inc.)

This paper focuses on vegetation health conditions (VHC) assessment and mapping using high resolution airborne hyperspectral AVIRIS-NG imagery and validated with field spectroscopy-based vegetation spectral data. It also quantified the effect of mining on vegetation health for geo-environmental impact assessment at a fine level scale. In this study, we have developed and modified vegetation indices (VIs) based model for VHC assessment and mapping in coal mining sites. We have used thirty narrow banded VIs based on the statistical measurement for suitable VIs identification. The highest Pearson's r, R 2 , lowest RMSE, and P values indices have been used for VIs combined pixels analysis. The highest different (Healthy vs. unhealthy) vegetation combination index (VCI) has been selected for VHC assessment and mapping. We have also compared VIs model-based VHC results to ENVI (software) forest health tool and Spectral-based SAM classification results. The 1st VCI result showed the highest difference (72.07%) from other VCI. The AUC values of the ROC curve have shown a better fit for the VIs model (0.79) than Spectral classification (0.74), and ENVI FHT (0.68) based on VHC results. The VHC results showed that unhealthy vegetation classes are located at low distances from mine sites, and healthy vegetation classes are situated at high distances. It is also seen that there is a highly significant positive relationship (R 2 =0.70) between VHC classes and distance from mines. These results will provide a guideline for geo-environmental impact assessment in coal mining sites., (Copyright © 2022. Published by Elsevier Inc.)

Background: Transcatheter aortic valve replacement (TAVR) is generally performed without control over the alignment of the bioprosthesis to the native aortic valve (AV) commissures. Data on the impact of commissural misalignment (CMA) on the clinical and hemodynamic outcome after TAVR are scarce., Objectives: The aim of this study was to investigate the impact of commissural misalignment (CMA) on the clinical and hemodynamic outcome in patients with severe tricuspid aortic stenosis undergoing TAVR using the balloon-expandable (BE) SAPIEN 3 valve (Edwards LifeSciences)., Methods: Clinical data of consecutive patients who underwent BE TAVR at Cedars-Sinai Medical Center (Los Angeles, California, USA) enrolled in the RESOLVE (Assessment of TRanscathetER and Surgical Aortic BiOprosthetic Valve Thrombosis and Its TrEatment With Anticoagulation) registry were retrospectively analyzed to evaluate CMA, which was defined as a neocommissure position >30° compared with native commissures on computed tomography., Results: A total of 324 patients (36.6% female, median Society of Thoracic Surgeons score of 3.9%) were included in the analysis. CMA was present in 171 individuals (52.8%). At 30 days, rates of aortic regurgitation greater than mild (5.6%) and a residual AV gradient ≥20 mm Hg (7.4%) were not different between CMA and non-CMA patients. Commissural orientation was independently associated with a relative AV mean gradient increase >50% from discharge to 30 days (per increase of 10° misalignment; OR: 1.3; 95% CI: 1.0-1.4; P = 0.01). The long-term composite outcome of death or stroke was not different between groups (log-rank P = 0.29)., Conclusions: In patients with severe tricuspid aortic stenosis who undergo SAPIEN 3 TAVR, the neocommissures align randomly. Our data demonstrate that commissural alignment may impact device performance and clinical outcomes in patients undergoing BE TAVR. (Assessment of TRanscathetEr and Surgical Aortic BiOprosthetic VaLVve Dysfunction with Multimodality Imaging and Its TrEatment with Anticoagulation [RESOLVE]; NCT02318342)., Competing Interests: Funding Support and Author Disclosures This research was supported by Cedars-Sinai Smidt Heart Institute and Leipzig Heart Institute. Dr Borger has received speakers’ honoraria and/or consultation fees from Edwards Lifesciences, Medtronic, Abbott, and CryoLife. Dr Chakravarty has served as a speaker and consultant for Edwards Lifesciences, Boston Scientific, Medtronic, and Abbott. Dr Makkar has received grant support from Edwards Lifesciences; has served as a consultant for Abbott Vascular, Cordis, and Medtronic; and owns equity in Entourage Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Introduction/background: With the advent of TransOral Robotic Surgery (TORS) the ease of transoral procedures has been dramatically improved. TORS is already established for its feasibility, functional and oncological outcomes for selected lesions of oral cavity, oropharynx and laryngopharynx. This study reports on preliminary results with TransOral UltraSonic Surgery (TOUSS) for oncologic resections of oral cavity, oropharyngeal and supraglottic malignancies., Materials and Methods: Eighteen patients with malignancies of oral cavity, oropharynx and supraglottis underwent TOUSS with simultaneous neck dissection and adjuvant therapy as indicated, from January 2018 to April 2019. Essential equipment included the FK-retractor (Gyrus Medical, Tuttilngen, Germany) for TransOral exposure, the Olympus ENDOEYE Flex 5 mm 2D/10 mm 3D deflecting tip video laparoscopes, and 35 cm long ultrasonic harmonic scalpel (Thunderbeat). Parameters evaluated include tumor staging, mouth opening, TOUSS setup time, TOUSS primary removal time, surgical margins, blood transfusions, tracheostomy, postoperative complications, enteral feeding and resumption of oral diet, duration of hospital stay, and survival outcomes., Results: Eighteen patients underwent complete TransOral UltraSonic Surgery (TOUSS), with simultaneous unilateral or bilateral neck dissection. No procedure was abandoned intraoperatively due to difficulty in extirpation of the tumor. Margins were negative for ten patients (55.6%), close in five (27.8%), and positive in three patients (16.7%). Average TOUSS set-up time was 22.5 min (range, 10-30 min) and average TOUSS primary tumor removal time was 35.3 min (range, 15-60 min). Patients started tolerating oral feeds even in the second post op day (mean 6 days), and transitioning to complete oral feeds with removal of the nasogastric tube was achieved in all (mean, 16 days). The average hospital stay was 7.4 days (range 2-16 days). Secondary hemorrhage occurred in two cases and required an emergency tracheostomy and ligation of lingual artery. Minor cervicopharyngeal fistula occurred in four cases and settled in all with conservative non-surgical treatment. Overall survival at 3 years was 70.5%, and disease-specific survival was 94.4%., Conclusion: TransOral UltraSonic Surgery (TOUSS) is a safe and sound alternative method of endoscopic surgical treatment of oral cavity, oropharynx and supraglottic neoplasms. Advantages of this technique include faster resection time, intraoperative assistance from Narrow Band Imaging, easy affordability compared to TORS, and excellent functional outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: We report the clinical efficacy against COVID-19 infection of BBV152, a whole virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) in Indian adults., Methods: We did a randomised, double-blind, placebo-controlled, multicentre, phase 3 clinical trial in 25 Indian hospitals or medical clinics to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Adults (age ≥18 years) who were healthy or had stable chronic medical conditions (not an immunocompromising condition or requiring treatment with immunosuppressive therapy) were randomised 1:1 with a computer-generated randomisation scheme (stratified for the presence or absence of chronic conditions) to receive two intramuscular doses of vaccine or placebo administered 4 weeks apart. Participants, investigators, study coordinators, study-related personnel, the sponsor, and nurses who administered the vaccines were masked to treatment group allocation; an unmasked contract research organisation and a masked expert adjudication panel assessed outcomes. The primary outcome was the efficacy of the BBV152 vaccine in preventing a first occurrence of laboratory-confirmed (RT-PCR-positive) symptomatic COVID-19 (any severity), occurring at least 14 days after the second dose in the per-protocol population. We also assessed safety and reactogenicity throughout the duration of the study in all participants who had received at least one dose of vaccine or placebo. This report contains interim results (data cutoff May 17, 2021) regarding immunogenicity and safety outcomes (captured on days 0 to 56) and efficacy results with a median of 99 days for the study population. The trial was registered on the Indian Clinical Trials Registry India, CTRI/2020/11/028976, and ClinicalTrials.gov, NCT04641481 (active, not recruiting)., Findings: Between Nov 16, 2020, and Jan 7, 2021, we recruited 25 798 participants who were randomly assigned to receive BBV152 or placebo; 24 419 received two doses of BBV152 (n=12 221) or placebo (n=12 198). Efficacy analysis was dependent on having 130 cases of symptomatic COVID-19, which occurred when 16 973 initially seronegative participants had at least 14 days follow-up after the second dose. 24 (0·3%) cases occurred among 8471 vaccine recipients and 106 (1·2%) among 8502 placebo recipients, giving an overall estimated vaccine efficacy of 77·8% (95% CI 65·2-86·4). In the safety population (n=25 753), 5959 adverse events occurred in 3194 participants. BBV152 was well tolerated; the same proportion of participants reported adverse events in the vaccine group (1597 [12·4%] of 12 879) and placebo group (1597 [12·4%] of 12 874), with no clinically significant differences in the distributions of solicited, unsolicited, or serious adverse events between the groups, and no cases of anaphylaxis or vaccine-related deaths., Interpretation: BBV152 was highly efficacious against laboratory-confirmed symptomatic COVID-19 disease in adults. Vaccination was well tolerated with no safety concerns raised in this interim analysis., Funding: Bharat Biotech International and Indian Council of Medical Research., Competing Interests: Declaration of interests This work was funded by Bharat Biotech International and co-funded by the Indian Council of Medical Research. RE, KMV, SPr, SRe, VKA and VS are employees of Bharat Biotech International, with no stock options or incentives. KE is the chairman and managing director of Bharat Biotech International and owns equity in the company. WB is an independent statistical development consultant. VP, PY, GS, PA, NG, BB, SK, and SPa are employees of the Indian Council of Medical Research. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The human coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 is now a global pandemic. Personal hygiene such as hand-washing, the use of personal protective equipment, and social distancing via local and national lockdowns are used to reduce the risk of transmission of SARS-CoV-2. COVID-19 and the associated lockdowns may have significant impacts on environmental quality and ergonomics. However, limited studies exists on the impacts of COVID-19 and the associated lockdowns on environmental quality and ergonomics in low-income settings. Therefore, the present study investigated the impacts of the COVID-19 outbreak on socioeconomics, ergonomics and environment (water quality, air quality and noise) in Uttarakhand, India. Approximately 55% of respondents experienced headaches, and the other common health-related issue was back pain, with 45% of respondents having problems with their backs. Water and air quality significantly improved during the lockdown relative to the pre-lockdown period, but was observed to return to their previous characteristics afterwards. Lockdowns significant increased the concentration of indoor air pollutants while noise pollution levels significantly declined. In summary, lockdowns have adverse impacts on ergonomics, resulting in work-related human health risks. The impacts of lockdowns on environmental quality are mixed: temporary improvements on water and air quality, and noise reduction were observed, but indoor air quality deteriorated. Therefore, during lockdowns there is a need to minimize the adverse environmental and ergonomic impacts of lockdowns while simultaneously enhancing the beneficial impacts., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier Ltd. All rights reserved.)

Problem: Postpartum haemorrhage [PPH] remains a major cause of maternal morbidity and mortality. Whilst low-resource settings bear the greatest burden of deaths, women live with associated morbidities in all healthcare settings. Limited data exists regarding the experience for women, their partners, or healthcare professionals [HCPs], affected by PPH., Aim: To qualitatively investigate the experience of PPH, for women (n=9), birth partners (n=4), and HCPs (n=9) in an inner-city tertiary referral centre. To provide multi-faceted insight into PPH and improve understanding and future care practices., Methods: Participants were interviewed about their experiences within two weeks of a PPH. Data were analysed using thematic analysis., Findings: Four distinct, but related, themes were identified: 'Knowledge specific to PPH'; 'Effective and appropriate responses to PPH'; 'Communication of risk factors'; and 'Quantifying blood loss'; which collected around a central organising concept of 'Explaining the indescribable'., Discussion: PPH was viewed as a 'crisis-style emergency', generating respectful fear in HCPs, whilst women and partners had little-to-no prior knowledge. Specific PPH knowledge dictated HCPs' response and risk communication. PPH risks were typically linked to quantification of blood loss, assessment of which varied with acknowledged questionable accuracy. Women's and partners' confidence in HCPs' ability to deal with PPH was unquestionable. Non-verbal communication was highlighted, with HCP body language betraying professional confidence., Conclusion: Information about blood loss during childbirth must be imparted in a sensitive, timely manner. Whilst training for HCPs results in effective PPH management, consideration should be given to their non-verbal cues and the impact of dealing with this stressful, 'everyday emergency'., (Copyright © 2020 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Trichinellosis is a zoonotic parasitic infection caused by nematodes of the genus Trichinella. Humans mostly get infected by eating raw/under-cooked pork. In India, it has been reported mostly as sporadic cases especially from North Eastern and Eastern part of country. In this study, we retrospectively analyzed the socio-demographic pattern, clinical presentation, laboratory profile and treatment response in Trichinella-infected patients visiting our tertiary care center which mainly caters to patients from North India. For this retrospective laboratory-based analysis, patients diagnosed on the basis of positive anti-Trichinella IgG antibodies between 1 st June 2008, and 31 st May 2019 were included. A total of 11 positive trichinellosis cases were detected, of whom majority were children who presented with history of fever, gastrointestinal symptoms, myalgia, eosinophilia along with hepatomegaly and pulmonary manifestations. No CNS involvement was seen in any of the patients although it is commonly associated with Trichinella infection. All patients recovered uneventfully after antihelminthic treatment., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Well-hydrated phospholipid bilayers provide a near-native environment for membrane proteins. They enable the preparation of chemically-defined samples suitable for NMR and other spectroscopic experiments that reveal the structure, dynamics, and functional interactions of the proteins at atomic resolution. The synthetic polymer styrene maleic acid (SMA) can be used to prepare detergent-free samples that form macrodiscs with diameters greater than 30 nm at room temperature, and spontaneously align in the magnetic field of an NMR spectrometer at temperatures above 35 °C. Here we show that magnetically aligned macrodiscs are particularly well suited for solid-state NMR experiments of membrane proteins because the SMA-lipid assembly both immobilizes the embedded protein and provides uniaxial order for oriented sample (OS) solid-state NMR studies. We show that aligned macrodiscs incorporating four different membrane proteins with a wide range of sizes and topological complexity yield high-resolution OS solid-state NMR spectra. The work is dedicated to Michelle Auger who made key contributions to the field of membrane and membrane protein biophysics., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

A new unusual seco-isopimarane, kaemgalangol A (1) and 12 usual analogs (2-13) were isolated from the rhizomes of Kaempferia galanga (Family: Zingiberaceae). KaemgalangolA (1) represented a rarely isolated 9,10-seco-isopimarane skeleton. The chemical structures of the isolated compounds were mainlyinvestigated by spectroscopic techniques such as 1D, 2D NMR, and HRMS. The absolute configuration of 1-3 was studied by X-ray diffraction analysis as well as experimental and TDDFT-calculated electronic circular dichroism. Among the isolated diterpenoids, 5, 6 and 9 exhibited cytotoxic activity against HeLa (IC 50 75.1, 74.2 and 76.5 μM, respectively) and HSC-2 (IC 50 69.9, 53.3 and 58.2 μM, respectively) cancer cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ovarian Sertoli-Leydig cell tumors (SLCT) represent <2% of primary ovarian tumors, which range from benign to malignant; majority of the latter are low-grade. We present the case of a 12-year-old pre-pubertal female with poorly differentiated SLCT and heterologous rhabdomyosarcoma (FIGO stage-IA). She presented with worsening abdominal pain, pelvic mass, and elevated pre-operative serum Alpha-fetoprotein (AFP, 77.1 ng/mL). She underwent right salpingo-oophorectomy, omentectomy, and lymphadenectomy. The high-risk histology warranted 4-cycles of adjuvant BEP chemotherapy. There was no clinical evidence of recurrence at the 20-month follow-up. High-grade sex cord-stromal tumors are rare, present with low-stage disease, and have good progression-free survival following chemotherapy. Rarity of these tumors poses challenges in their diagnosis and treatment. Review of literature suggests that the presented case is youngest patient with dedifferentiated SLCT.

Integrins are the major cell adhesion glycoproteins involved in cell-extracellular matrix (ECM) interaction and metastasis. Further, glycosylation on integrin is necessary for its proper folding and functionality. Herein, differential expression of integrins viz., αvβ3 and αvβ6 was examined in MDA-MB-231, MDA-MB-468 and MCF-10A cells, which signify three different stages of breast cancer development from highly metastatic to non-tumorigenic stage. The expression of αvβ3 and αvβ6 integrins at mRNA and protein levels was observed in all three cell lines and the results displayed a distinct pattern of expression. Highly metastatic cells showed enhanced expression of αvβ3 than moderate metastatic and non-tumorigenic cells. The scenario was reversed in case of αvβ6 integrin, which was strongly expressed in moderate metastatic and non-tumorigenic cells. N-glycosylation of αvβ3 and αvβ6 integrins is required for the attachment of cells to ECM proteins like fibronectin. The cell adhesion properties were found to be different in these cancer cells with respect to the type of integrins expressed. The results testify that αvβ3 integrin in highly metastatic cells, αvβ6 integrin in both moderate metastatic and non-tumorigenic cells play an important role in cell adhesion. The investigation typify that N-glycosylation on integrins is also necessary for cell-ECM interaction. Further, glycosylation inhibition by Swainsonine is found to be more detrimental to invasive property of moderate metastatic cells. Conclusively, types of integrins expressed as well as their N-glycosylation pattern alter during the course of breast cancer progression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neurotransmitters are signaling molecules which play a key role in the central nervous system allowing signal transmission in the neuronal synapses. The role of these compounds is very crucial in the biological systems. A rapid, sensitive, economical and derivatisation free method has been developed for the analysis of 15 neurotransmitters in a single run on liquid chromatography tandem mass spectrometry. These 15 neurotransmitters are categorized into 5 groups on the basis of their fragmentation pattern. The proposed method "ionic liquid based ultrasound assisted dispersive liquid-liquid microextraction" hyphenated with tandem mass spectrometry is the first report for the analysis of neurotransmitters in cell samples along with other two matrices (rat brain and plasma). All the parameters that influence the extraction efficiency are optimized with aid of response surface methodology and desirability profile. Under these optimized conditions the developed method has been validated. The limit of detection was in the range of (1) 0.021-0.912 μg L -1 for rat brain samples, (2) 0.028-0.978 μg L -1 for plasma samples and (3) 0.025-0.945 μg L -1 for cell samples with good linearity behavior for all analytes in the concentration range of 0.04-200 μg L -1 in all the three matrices. The coefficient of determination for all the neurotransmitters was found in the range of (1) (R 2 ) ≥ 0.996 to 0.999 for rat brain samples and (2) (R 2 ) ≥ 0.991 to 0.999 for plasma and cell samples. The intra-day and inter-day variations were found less than (1) 1.78% and 8.94% for rat brain samples, (2) 1.83% and 8.37% for plasma samples and (3) 1.64% and 8.04% for cell samples respectively. The method has mean recoveries varied between (1) 81-128% for brain samples, (2) 88-107% for plasma samples and (3) 91-104% for cell samples at different spiking levels. The optimized and validated method was found free from matrix interferences and successfully applied for quantitative determination of 15 neurotransmitters in the rat brain, plasma and cell samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Enveloped viruses enter cells by using their fusion proteins to merge the virus lipid envelope and the cell membrane. While crystal structures of the water-soluble ectodomains of many viral fusion proteins have been determined, the structure and assembly of the C-terminal transmembrane domain (TMD) remains poorly understood. Here we use solid-state NMR to determine the backbone conformation and oligomeric structure of the TMD of the parainfluenza virus 5 fusion protein. 13 C chemical shifts indicate that the central leucine-rich segment of the TMD is α-helical in POPC/cholesterol membranes and POPE membranes, while the Ile- and Val-rich termini shift to the β-strand conformation in the POPE membrane. Importantly, lipid mixing assays indicate that the TMD is more fusogenic in the POPE membrane than in the POPC/cholesterol membrane, indicating that the β-strand conformation is important for fusion by inducing membrane curvature. Incorporation of para-fluorinated Phe at three positions of the α-helical core allowed us to measure interhelical distances using 19 F spin diffusion NMR. The data indicate that, at peptide:lipid molar ratios of ~1:15, the TMD forms a trimeric helical bundle with inter-helical distances of 8.2-8.4Å for L493F and L504F and 10.5Å for L500F. These data provide high-resolution evidence of trimer formation of a viral fusion protein TMD in phospholipid bilayers, and indicate that the parainfluenza virus 5 fusion protein TMD harbors two functions: the central α-helical core is the trimerization unit of the protein, while the two termini are responsible for inducing membrane curvature by transitioning to a β-sheet conformation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Temporary confinement during parturition and early postpartum may provide an intermediary step preceding loose housing that offers improvement in sow and piglet welfare. Three experiments were conducted to investigate the implications of replacing farrowing crates (FCs) with an alternative housing system from 3 days postpartum until weaning. In each experiment sows farrowed in FCs and were randomly allocated at day 3 of lactation to either a FC or a pen with increased floor space (lactation pen (LP)) until weaning. In experiment 1, piglet growth and sow and piglet skin injuries were recorded for 32 sows and 128 focal piglets in these litters. Behaviour around nursing and piglet behavioural time budgets were also recorded for 24 of these litters (96 focal piglets for time budgets). In experiment 2, measures of skin injury and behavioural time budgets were conducted on 28 sows and 112 focal piglets. The behavioural response of sows to piglet vocalisation (maternal responsiveness test (MRT)) was also assessed. In experiment 3, piglet mortality from day 3 of lactation until weaning was recorded in 672 litters over 12 months. While housing did not affect piglet weight gain in experiment 1, or piglet skin injuries in experiments 1 or 2, sows in both experiments sustained more injuries in LP than FC (experiment 1, 2.9 v. 1.4; experiment 2, 2.5 v. 0.8 lesions/sow; P0.05). Thus, housing sows and litters in LP from day 3 of lactation minimises piglet mortality while improving maternal behaviour in sows and social behaviour in piglets.

Background: Takayasu arteritis, also known as "pulseless disease," causes proximal occlusion of the lumen of large arteries of the neck and arm, leading to impalpable pulses and "pseudohypotension." This may misdirect the management plan for a patient in the emergency setting if the presence of vascular occlusion is not previously known., Case Report: We describe a young woman who presented to the emergency department (ED) with fever. On evaluation, she had shock, which was not responsive to a fluid bolus. Bedside Rapid Diagnostic Test was positive for Plasmodium vivax, and a diagnosis of severe vivax malaria was made. She was started on intravenous artesunate and vasopressors in view of her persistent hypotension in the face of a normal central venous pressure. A thorough examination at that time revealed palpable lower limb pulses with feeble upper limb pulses. Vasopressors were tapered while monitoring lower limb blood pressure. Computed tomographic angiogram confirmed the diagnosis of Takayasu arteritis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Hypotension and shock are regularly encountered in the ED. Occlusive arterial disease involving upper limbs can mimic refractory shock, leading to potentially harmful and unnecessary interventions. Emergency physicians should be aware of this possibility. A simple routine of quickly checking all peripheral pulses would help them avoid this pitfall., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Originally introduced for mandibular reconstruction more than 40 years ago, the sternoclavicular graft (SCG) has gained widespread popularity for the reconstruction of the ramus-condyle unit (RCU) owing to its anatomic and histological likeness to the normal mandibular condyle. Conventional longitudinal osteotomy design for its harvest has been fraught with considerable complications at the donor site including fracture clavicle and major neurovascular injury. In an attempt to alleviate these ill effects, a new technique for procuring the sternoclavicular graft is presented., Material and Methods: A split-thickness cortico-cancellous graft was harvested form the sternal end of the clavicle along with the articular disk with the osteotomy cut oriented parallel to the coronal plane, with limited soft tissue dissection. Donor site complications were assessed in terms of incidence of clavicle fracture, neurovascular injury, pleural tear and radiographic healing as seen in the six-month postoperative chest radiograph., Results: 17 patients suffering from unilateral temporomandibular joint ankylosis underwent SCG harvesting for RCU reconstruction following osteoarthrectomy. No adverse events were seen in the intra- and post-operative period in any patient and satisfactory radiographic osseous healing was observed after six months., Conclusion: The proposed harvest technique for SCG results in reduced donor site morbidity and favourable healing and greater patient comfort., (Copyright © 2016. Published by Elsevier Ltd.)

Background: The purpose of this study was to evaluate the influence of Charlson indices and comorbid conditions on the risk of perioperative complications in bilateral simultaneous total knee arthroplasty (BSTKA)., Methods: In our retrospective analysis, 556 patients including 133 males and 423 females (mean age 65.8years), who had undergone bilateral simultaneous total knee arthroplasty between 2011 and 2014 were included. Risk factors (Charlson comorbidity index (CCI), age-adjusted Charlson comorbidity index (ACCI), and comorbid illnesses) and perioperative complications were noted, and subsequently, statistical tests were applied., Results: There was significant association between Charlson indices and most of the complications (P<0.05) with high-risk ACCI groups (a score>5) bearing maximum odds for cumulative major complication (OR 4.165, P<0.001, 95% CI 1.874 to 9.256). In addition, hypertension, non-ischemic cardiac illness, and moderate to severe chronic kidney disease proved be to be determinants for major complications (P=0.031, P=0.041, and P=0.014, respectively). We also found significant associations between organ-specific illnesses and complications such as cardiac, pulmonary, neurological and renal complications (P<0.05)., Conclusions: Both CCI and ACCI are predictors of post-operative complications with ACCI being the better predictive determinant. Hence, these predictors should be used for risk stratification prior to patient selection for BSTKA. The influence of hypertension, non-ischemic cardiac illness and moderate to severe chronic kidney disease should also be considered during patient selection. Moreover, optimum organ function at the time of surgery should be a priority to avoid these complications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Control of bacteriuria is problematic in patients who perform clean intermittent catheterization for management of neurogenic bladder. This population is often burdened with multiple urinary tract infections (UTIs), placing them at increased risk of end-stage renal disease. Hydrophilic catheters are a potential way to improve smooth and clean insertion, reduce disruption of the urothelium, and reduce bacterial colonization., Objective: The goal of the study was to compare the type and virulence of microorganisms recovered from the urine of patients that use either a hydrophilic or conventional polyvinyl chloride (PVC) catheter., Methods: Fifty patients with an underlying diagnosis of myelomeningocele were recruited for a 12-month prospective, randomized, investigator-blinded study. Twenty-five patients were allocated to the hydrophilic catheter intervention, and 25 continued use of a PVC catheter. Cultures were performed on urine obtained by catheterization at enrollment, and 3, 6, and 12 months. Bacterial species were assigned a designation as either potentially pathogenic or non-pathogenic. Escherichia coli isolates were the most predominant and were serotyped to further stratify the pathogenicity of the strains. Lastly, patients were surveyed at enrollment, and at the two later time points evaluating their current catheter for satisfaction., Results: A total of 232 different bacterial isolates were obtained from the 182 collected urine cultures. In addition, seven species were recovered from the two UTI reported during the study period. Bacterial growth was not detected in 29 of the samples (16%). Although not statistically significant, collectively there was a 40% decrease in the average number of potentially pathogenic species recovered from those patients using hydrophilic catheters (0.81 per urine sample) compared with PVC catheter use (1.24 per urine sample). Since E. coli species can be either pathogenic or non-pathogenic, we examined 14 of the most commonly implicated serotypes associated with uropathogenic E. coli (UPEC). We identified the serotype of 57% of E. coli strains recovered. There was a trend for the recovery of fewer UPEC serotypes from the hydrophilic group (54% hydrophilic verses 64% PVC), further suggesting that the catheter type may influence the microbiological milieu. Although no significant differences were reported in patient satisfaction, almost half of the patients from the hydrophilic catheter cohort continue use of this type of catheter., Conclusions: There was a trend for reduced recovery of potentially pathogenic bacteria with the use of hydrophilic catheters. The reduction in potentially pathogenic species will reduce antibiotic exposures and some patients may prefer the comfort hydrophilic catheters provide., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Bone allografts (BA) are a cost-effective and sustainable alternative in orthopedic practice as they provide a permanent solution for preserving skeletal architecture and function. Such BA however, must be processed to be disease free and immunologically safe as well as biologically and clinically useful. Here, we have demonstrated a processing protocol for bone allografts and investigated the micro-structural properties of bone collected from osteoporotic and normal human donor samples. In order to characterize BA at different microscopic levels, a combination of techniques such as Solid State Nuclear Magnetic Resonance (ssNMR), Scanning Electron Microscope (SEM), micro-computed tomography (μCT) and Thermal Gravimetric Analysis (TGA) were used for delineating the ultra-structural property of bone. ssNMR revealed the extent of water, collagen fine structure and crystalline order in the bone. These were greatly perturbed in the bone taken from osteoporotic bone donor. Among the processing methods analyzed, pasteurization at 60 °C and radiation treatment appeared to substantially alter the bone integrity. SEM study showed a reduction in Ca/P ratio and non-uniform distribution of elements in osteoporotic bones. μ-CT and MIMICS (Materialize Interactive Medical Image Control System) demonstrated that pasteurization and radiation treatment affects the BA morphology and cause a shift in the HU unit. However, the combination of all these processes restored all-important parameters that are critical for BA integrity and sustainability. Cross-correlation between the various probes we used quantitatively demonstrated differences in morphological and micro-structural properties between BA taken from normal and osteoporotic human donor. Such details could also be instrumental in designing an appropriate bone scaffold. For the best restoration of bone microstructure and to be used as a biomaterial allograft, a step-wise processing method is recommended that preserves all critical parameters of bone, showing a significant advancements over currently existing methods., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Autologous vein-graft failure significantly limits the long-term efficacy of coronary artery bypass procedures. The major cause behind this complication is biomechanical mismatch between the vein and coronary artery. The implanted vein experiences a sudden increase (10-12 fold) in luminal pressures. The resulting vein over-distension or 'ballooning' initiates wall thickening phenomenon and ultimate occlusion. Therefore, a primary goal in improving the longevity of a coronary bypass procedure is to inhibit vein over-distension using mechanical constriction. The idea of using an external vein-graft support mesh has demonstrated sustained benefits and wide acceptance in experimental studies. Nitinol based knitted structures have offered more promising mechanical features than other mesh designs owing to their unique loosely looped construction. However, the conventional plain knit construction still exhibits limitations (radial compliance, deployment ease, flexibility, and bending stresses) which limit this design from proving its real clinical advantage. The new knitted mesh design presented in this study is based on the concept of composite knitting utilising high modulus (nitinol and polyester) and low modulus (polyurethane) material components. The experimental comparison of the new design with a plain knit design demonstrated significant improvement in biomechanical (compliance, flexibility, extensibility, viscoelasticity) and procedural (deployment limit) parameters. The results are indicative of the promising role of new mesh in restoring the lost compliance and pulsatility of vein-graft at high arterial pressures. This way it can assist in controlled vein-graft remodelling and stepwise restoration of vein mechanical homoeostasis. Also, improvement in deployment limit parameter offers more flexibility for a surgeon to use a wide range of vein diameters, which may otherwise be rendered unusable for a plain knit mesh., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Oxidative stress is implicated in toxicant-induced inflammation leading to chronic diseases. Polymorphonuclear leukocytes (PMNs) offer the first line of defense against infection in the mammals and protect against inflammation-mediated pathological anomalies. Conversely, activated PMNs contribute to the oxidative stress-mediated damage and inflammation. The study aimed to investigate the status of oxidative stress and antioxidant defense system in the PMNs of rats treated with/without zinc (Zn) and/or paraquat (PQ) in the presence or absence of a synthetic superoxide dismutase/catalase mimetic, a manganese-salen compound-EUK-134 and/or a glutathione precursor, N-acetyl cysteine (NAC). While Zn and/or PQ elevated the total free radical generation, lipid peroxidation (LPO) and catalytic activity of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase alpha 4-4 (GSTA4-4), a pronounced decrease in reduced glutathione (GSH) and glutathione reductase (GR) activity was also observed. Zn and/or PQ augmented the expression of metallothionein-I and II and GSTA4-4. Pre-treatment of EUK-134 or NAC alone altered the level of total free radical generation, LPO, GSH content and catalytic activity of MPO, SOD, GR and GPx and the expression of metallothionein I and II towards normalcy. The alterations were more pronounced in the PMNs of rats treated with EUK-134 and NAC in combination. Catalytic activity/expression of GSTA4-4 remained unchanged in the PMNs of EUK-134 or NAC treated rats. The results demonstrate that EUK-134 and NAC protect PMNs from the toxic effects of Zn and PQ in rats and also suggest that metallothioneins I/II might contribute to antioxidant defense under GSH depleted conditions., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Melanoma causes more deaths than any other skin cancer, and its incidence in the US continues to rise. Current medical therapies are insufficient to control this deadly neoplasm, necessitating the development of new target-based approaches. The objective of this study was to determine the role and functional significance of the class III histone deacetylase SIRT1 in melanoma. We have found that SIRT1 is overexpressed in clinical human melanoma tissues and human melanoma cell lines (Sk-Mel-2, WM35, G361, A375, and Hs294T) compared to normal skin and normal melanocytes, respectively. In addition, treatment of melanoma cell lines A375, Hs294T, and G361 with Tenovin-1, a small molecule SIRT1 inhibitor, resulted in a significant decrease in cell growth and cell viability. Further, Tenovin-1 treatment also resulted in a marked decrease in the clonogenic survival of melanoma cells. Further experiments showed that the anti-proliferative response of Tenovin-1 was accompanied by an increase in the protein as well as activity of the tumor suppressor p53. This increase in p53 activity was substantiated by an increase in the protein level of its downstream target p21. Overall, these data suggest that small molecule inhibition of SIRT1 causes anti-proliferative effects in melanoma cells. SIRT1 appears to be acting through the activity of the tumor suppressor p53, which is not mutated in the majority of melanomas. However, future detailed studies are needed to further explore the role and mechanism of SIRT1 in melanoma development and progression and its usefulness in melanoma treatment.

Stent-graft (SG) induced biomechanical mismatch at the aortic repair site forms the major reason behind postoperative hemodynamic complications. These complications arise from mismatched radial compliance and stiffness property of repair device relative to native aortic mechanics. The inability of an exoskeleton SG design (an externally stented rigid polyester graft) to achieve optimum balance between structural robustness and flexibility constrains its biomechanical performance limits. Therefore, a new SG design capable of dynamically controlling its stiffness and flexibility has been proposed in this study. The new design is adopted from the segmented hydroskeleton structure of a caterpillar cuticle and comprises of high performance polymeric filaments constructed in a segmented knit architecture. Initially, conceptual design models of caterpillar and SG were developed and later translated into an experimental SG prototype. The in-vitro biomechanical evaluation (compliance, bending moment, migration intensity, and viscoelasticity) revealed significantly better performance of hydroskeleton structure than a commercial SG device (Zenith(™) Flex SG) and woven Dacron(®) graft-prosthesis. Structural segmentation improved the biomechanical behaviour of new SG by inducing a three dimensional volumetric expansion property when the SG was subjected to hoop stresses. Interestingly, this behaviour matches the orthotropic elastic property of native aorta and hence proposes segmented hydroskeleton structures as promising design approach for future aortic repair devices., (© 2013 Published by Elsevier Ltd.)

Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is increasingly becoming a popular technique to probe micro-structural details of biomaterial such as bone with pico-meter resolution. Due to high-resolution structural details probed by SSNMR methods, handling of bone samples and experimental protocol are very crucial aspects of study. We present here first report of the effect of various experimental protocols and handling methods of bone samples on measured SSNMR parameters. Various popular SSNMR experiments were performed on intact cortical bone sample collected from fresh animal, immediately after removal from animal systems, and results were compared with bone samples preserved in different conditions. We find that the best experimental conditions for SSNMR parameters of bones correspond to preservation at -20 °C and in 70% ethanol solution. Various other SSNMR parameters were compared corresponding to different experimental conditions. Our study has helped in finding best experimental protocol for SSNMR studies of bone. This study will be of further help in the application of SSNMR studies on large bone disease related animal model systems for statistically significant results., (© 2013 Elsevier Inc. All rights reserved.)

Oxidative stress is one of the major players in the pathogenesis of maneb (MB) and paraquat (PQ)-induced disorders. N-acetyl cysteine (NAC), a glutathione (GSH) precursor and silymarin (SIL), a naturally occurring antioxidant, encounter oxidative stress-mediated cellular damage. The present study was aimed to investigate the effects of NAC and SIL against MB and/or PQ-induced hepatotoxicity in rats. The levels of hepatotoxicity markers - alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and total bilirubin, histological changes, oxidative stress indices, phase I and phase II xenobiotic metabolizing enzymes - cytochrome P450 (CYP) and glutathione S-transferase (GST) and pro-inflammatory molecules - inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured in animals treated with MB and/or PQ in the presence or absence of NAC and SIL. MB and/or PQ augmented ALT, AST, total bilirubin, lipid peroxidation and nitrite contents and catalytic activities of superoxide dismutase and glutathione peroxidase however, the GSH content was attenuated. NAC and SIL restored the above-mentioned alterations towards basal levels but the restorations were more pronounced in SIL treated groups. Similarly, MB and/or PQ-mediated histopathological symptoms and changes in the catalytic activities/expressions of CYP1A2, CYP2E1, iNOS, TNF-α, and IL-1β were alleviated by NAC and SIL. Conversely, MB and/or PQ-induced GSTA4-4 expression/activity was further increased by NAC/SIL and glutathione reductase activity was also increased. The results obtained thus suggest that NAC and SIL protect MB and/or PQ-induced hepatotoxicity by reducing oxidative stress, inflammation and by modulating xenobitic metabolizing machinery and SIL seems to be more effective., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)