Influence of Defect Engineering in Nanocrystalline CeO2 for Therapeutics of Reactive Oxygen Species-mediated Disorders.

Intracellular oxidative stress generation is a root cause of the dysfunctioning of mitochondria that is accountable for neurodegenerative disorders. In nano-CeO2, the intrinsic redox cycle (Ce3+ ⇔ Ce4+) confers them with a distinct oxygen buffering ability. Thus, increasing the Ce3+/Ce4+ ratio by preferentially engineering oxygen vacancies is expected to boost the antioxidant characteristics in CeO2 nanocrystals (NCs) and hold promise in nanotherapeutics of neurodegenerative disorders. Here, a pristine, economic, and scalable synthesis route with rapid nucleation-growth to yield monodispersed CeO2 NCs of 4 nm has been employed. The NCs demonstrated sustained colloidal stability (zeta potential ~ -30.3±7.2 mV). The survival rate (~96.1% for 0.1 mg/mL) of healthy L929 cells and cell apoptosis induced on the SH-SY5Y cells (~ 30.2% for 0.1 mg/mL) indicate nano-CeO2s' prospects in nanomedicine. The formulated sustainable synthesis strategy for the enrichment of defects in these NCs is anticipated to pave the way for nanocrystal-based-treatments in smart healthcare.Clinical Relevance-This investigation signifies the oxygen vacancy-dependent therapeutic efficacy of CeO2 NCs by ensuring ~96.1% survival rate of L929 cells while demonstrating cell apoptosis on SH-SY5Y cells (~ 30.2%) to establish newer insights on treatment of neurodegenerative disorders.

Deaths due to hydrogen sulphide on a jack up rig at Bombay High: an avoidable accident.

An enclosed space is an area with poor or no natural ventilation which is not designed for continuous occupancy, where access is limited and which may contain a dangerous atmosphere. Enclosed space atmospheres can be hazardous due to one or a combination of the conditions which includes oxygen deficiency; presence of toxic and/or flammable gases. When it is intended that personnel should enter or work in an enclosed space, care should be taken to create and maintain safe working conditions. The case report describes an incident on board an oil rig where the rig workers were exposed to noxious gases resulting in multiple fatalities. Work involved gas sampling/monitoring at various locations inside the "spud tanks" of the rig and certifying it free of noxious gases for marine surveyor's inspection. Contributory factors that have been frequently identified following enclosed space accident investigations are non-compliance with procedures, inappropriate equipment, poor supervision, complacency and over familiarity leading to short cuts being taken, detection and monitoring equipment not used or not working properly and improper action in an emergency. Preventive measures to avoid such accidents and create a safe working area are discussed.

Functionality Tuning in Hierarchically Engineered Magnetoelectric Nanocomposites for Energy-Harvesting Applications.

The ß-phase of the copolymer poly(vinylidene fluoride-trifluoroethylene) P(VDF-TrFE) possesses the highest dipole moment among all the functional polymers. It remains a key component of flexible energy-harvesting devices based on piezoelectricity and triboelectricity in the last decade. However, the quest for P(VDF-TrFE)-based magnetoelectric (ME) nanocomposites with enhanced ferroelectric, piezoelectric, and triboelectric properties remains elusive. The magnetostrictive inclusion in the copolymer matrix forms electrically conducting pathways and degrades ß-phase crystallinity significantly, deteriorating the functional properties of the nanocomposite films. To address this issue, we report the synthesis of magnetite (Fe3O4) nanoparticles on micron-scale magnesium hydroxide [Mg(OH)2] templates. These hierarchical structures were incorporated within the P(VDF-TrFE) matrix rendering composites with enhanced energy-harvesting capability. The Mg(OH)2 template prevents the formation of a continuous network of magnetic fillers, leading to lower electrical leakage in the composite. The addition of dual-phase fillers with 5 wt % only increases remanent polarization (Pr) values by ∼44%, owing to the presence of the ß-phase with significant crystallinity and increased interfacial polarization. The composite film exhibits a quasi-superparamagnetic nature and a significant magnetoelectric coupling coefficient (αME) of 30 mV/cm Oe. The film was also employed for triboelectric nanogenerator applications, exhibiting five times higher power density than the pristine film. We finally explored the integration of our ME devices with an internet of things platform to monitor the operational status of electrical appliances remotely. In light of these findings, the present work opens the path for future self-powered, multifunctional, and flexible ME devices with new application domains.

Safety and efficacy of mycophenolate in COVID-19: a nonrandomised prospective study in western India.

Background: Antivirals and immunosuppressive agents are used with variable success in the treatment of COVID-19. Mycophenolate, an inhibitor of enzyme inosine monophosphate dehydrogenase, is an immunosuppressant used to prevent allograft rejection and other autoimmune diseases. Few laboratory studies have also reported antiviral properties of mycophenolate. The current study tried to assess the safety and efficacy of mycophenolate in patients hospitalised with COVID-19. Methods: This was a prospective non-randomised open label study with the objective to assess the effect of addition of mycophenolate to the standard of care on mortality due to COVID-19 and duration of hospital stay. The target study population was comprised of patients requiring inpatient treatment for COVID-19 during the period from Jan 15-April 15, 2021. The study was registered with Clinical Trial Registry of India (CTRI/2021/01/030477, registered on date-14/01/2021). Adult patients (n = 106) requiring hospitalisation for COVID-19 received mycophenolate, 360 mg, one tablet daily for one month. Mycophenolate was initiated within 48 h of the diagnosis of SARS-CoV-2 infection by RT‒PCR. While patients who did not consent for mycophenolate (n = 106), received only standard of care, and were considered as control group. The relevant clinical data including NEWS2 scores and high-resolution computed tomography of the thorax were collected and analysed. Findings: The mortality and hospital stay were significantly lower in the study group compared to the control group. Mycophenolate significantly reduced mortality after adjustment for other predictors (adjusted odds ratio: 0.082 with 95% CI: 0.012-0.567). Mycophenolate was an independent predictor of survival in patients hospitalised due to COVID-19. There was also no evidence of secondary bacterial infections and post-COVID complications. Interpretation: Mycophenolate administration is safe in COVID-19. Mycophenolate reduces mortality and duration of hospital stay in patients with COVID-19. Funding: Shri Janai Research Foundation, India.

Lyophilized Platelet-rich plasma for the management of thin endometrium and facilitation of in-vitro fertilization.

OBJECTIVE: Adequate endometrial thickness has been considered an important parameter for hormonal response and blastocyst implantation in assisted reproduction therapies. While there is no consensus on the exact thickness of the endometrium considered 'adequate,' a thin endometrium (<7mm) has been associated with compromised outcomes in assisted reproduction therapies. Platelet-rich plasma (PRP), which is a concentrate obtained from peripheral blood, is a rich source of growth factors that play important roles in various cellular processes. The objective is to utilize lyophilized PRP (LPRP) to increase the thickness of the endometrium and enhance the outcomes of embryo transfer in women with poor response to previous in-vitro fertilization procedures. METHODS: This study enrolled nine women between 23 and 42 years of age, with a thin endometrium, who had undergone multiple previous unsuccessful assisted reproduction procedures. All patients underwent intrauterine infusion of LPRP, followed by frozen-thawed embryo transfer after 2-3 days. RESULTS: Endometrial thickness was assessed by ultrasound 2 weeks after LPRP infusion, which showed improved thickness in all patients (range, 0.7-2.2mm). Clinical pregnancy occurred in all patients and eight out of nine patients are currently between 9 weeks and 27 weeks of gestation. Twin fetal heartbeats were not detected at the eighth week in one patient. CONCLUSION: Infusion of LPRP was found to be beneficial to increase endometrium thickness in all patients. This regenerative technique could be considered to enhance the outcomes of assisted reproduction techniques in a minimally-invasive manner, without any side effects.

A review of accelerated decompression from heliox saturation in commercial diving emergencies.

INTRODUCTION: Saturation diving is a specialised method of intervention in offshore commercial diving. Emergencies may require the crew to be evacuated from the diving support vessel. Because saturation divers generally need several days to reach surface, the emergency evacuation of divers is based on dedicated hyperbaric rescue systems. There are still potential situations for which these systems cannot be used or deployed, and where an emergency decompression provides an alternative solution. METHODS: Our objective was to describe historical cases and assess the benefit of emergency decompressions, with the collection of data from the authors' direct experience and networks, providing witness or first-hand information. RESULTS: We documented three cases of emergency decompression following bell evacuations, and six cases of accelerated decompression performed in the chamber or hyperbaric rescue chamber. Review of these cases showed: 1) the complicated nature of such emergencies that make decisions difficult; 2) the variety of solutions implemented; and 3) the surprisingly safe and successful outcomes of several operations. Analysis of the accelerated decompression occurrences allowed derivation of the options used; upward initial excursion, increased chamber partial pressure of oxygen associated to increased ascent rates, and inert gas switching. We identified four published procedures for accelerated decompression. CONCLUSIONS: Despite modern hyperbaric rescue systems, accelerated decompression remains an essential tool in case of emergency. The diving industry needs clear guidance on what can be achieved, depending on the saturation depth and the level of emergency.

Continuous flow scale-up of biofunctionalized defective ZnO quantum dots: A safer inorganic ingredient for skin UV protection.

The versatility of ZnO quantum dots (QDs) exhibiting size-tunable visible photoluminescence has propelled them to the forefront of leading-edge innovations in healthcare. At the nano-bio interface, enhancing the singly-ionized oxygen vacancy defects (VO•) through holistic, sustainable synthesis protocols driven by the synergistic influence of QDs' nucleation-growth kinetics has implications on their bioactivity, physiochemical, and optical performance. Recently, robust continuous flow platforms have transcended the conventional batch reactors by alleviating the concerns of "hot-spot" formation due to inhomogeneous heat distribution, acute energy consumption, poor quality, and yield. However, complexities exist in translating batch chemistries into flow processes. Here, a unique, rationally designed continuous flow synthesis of luminescent defect-engineered ZnO QDs (E-QDs) via helical-reactor assembly that can adequately synthesize on a large scale is reported. The crux of this lies in the amalgamation of "green chemistry" and flow synthesis, which results in Lamer-mechanism mediated monodispersed E-QDs demonstrating high photoluminescence quantum yield (PLQY) of 89% under an accurately regulated synthesis environment. Process intensification corroborated that the bio-stable E-QDs manifested admirable photostability, broad-spectrum UV-shielding (400-250 nm), colloidal stability, in vitro biocompatibility against L929 and HaCaT cells, and antioxidant activity. These attributes were better compared to the commercial ZnO nanoparticles (ZnOC-NPs) used for skin UV protection. Delving deeper, the main drivers for the high density of intrinsic VO• formation (Iv/Io∼42.5) were revealed to be the reactor's hydrodynamic performance and the improvised heating rate (2.5°C/sec). Hence, these E-QDs have potential as a new, safe, and economical multifunctional active ingredient for skin UV protection and antioxidants for treating ROS-mediated disorders. STATEMENT OF SIGNIFICANCE: UV filters exhibiting questionable UV-attenuation efficacy and phototoxicity are significant impediments to the healthcare industry emphasizing skin cancer prevention. Although least explored, VO•-governed aberrant photoactive, biological, and surface-reactive qualities of engineered ZnO QDs (E-QDs) have created ample room to investigate these hallmarks for skin UV protection. However, the bottlenecks in stereotypical ZnO QDs production confined by inefficient process control are annihilated by continuous flow strategies. Herein, the high-throughput continuous flow helical reactor assembly was designed and fabricated to successfully showcase optimized transport properties, reproducibility, yield, and quality E-QDs. Anticipating a skyrocketing demand for E-QDs as bioactive-sunscreen components, the comprehensive investigation has demonstrated unprecedented biofunctionality and ROS-scavenging behaviour, even upon UVR exposure, contrary to the traditional nanoparticulate ZnO UV filters.

Rescue of a saturation diver, unconscious due to an explosion underwater.

Evolution of "safe diving practices" introduced by the diving industry and regulatory authorities in the North Sea over the past 3 or 4 decades has improved the safety records of oilfield commercial diving considerably. However, accidents still occur. In an accident occurring underwater, the outcome is often fatal. For a diving doctor providing emergency medical advice to the industry, when a diving superintendent calls to say "I have a problem" indicates an emergency and a life and death situation for a diver in water. Making a quick decision after comprehending the situations is important to tackle the problem.

Saturation diver fatality due to hydrogen sulphide while working on a subsea pipe line.

In the offshore oil industry, Multipurpose Support Vessels with extensive diving capability are used for inspection, maintenance and repair of subsea pipelines. The diving industry has developed systemic safety checks and strict regulatory control after a number of fatal accidents in early years. However, accidents do continue to occur and, when involving divers in the water, are often fatal. Hydrogen sulphide (H2S), called 'sour gas' in an oil field, is produced by the action of anaerobic bacteria on sulphate containing organic matter. A highly toxic gas, it remains a constant danger for offshore oil industry workers who must remain vigilant. Crude oil and gas produced in these oilfields is called 'sour crude' and pipelines carry this crude with varying content of dissolved H2S to shore for processing. Divers are routinely called to attend to leaking pipelines and come in contact with this crude. Their hot water suits and umbilical lines are often covered with crude containing dissolved H2S. There is always a possibility that these may enter and contaminate the bell environment. Such a case leading to fatality is reported here.

A case of neurocysticercosis with an unusual presentation on high seas.

Every seafarer undergoes a medical examination prior to joining a ship. Some disorders cannot be detected and they may appear while at sea. Diagnosing and managing them becomes extremely difficult for the Master being the caregiver on board. Large crude carriers often perform long voyages and due to their sheer size, do not enter any port. Helicopter evacuation of a sick or injured crew is the norm. They operate under strict chartering time lines which do not permit deviation from course. A case of hemiparesis on left side of body in a young hitherto healthy seafarer which was later diagnosed as a case of neurocysticercosis is described.

QSPR Modeling of Biopharmaceutical Properties of Hydroxypropyl Methylcellulose (Cellulose Ethers) Tablets Based on Its Degree of Polymerization.

Quantitative structure-property relationship (QSPR) approach has been widely used in predicting physicochemical properties of compounds. However, its application in the estimation of formulation properties based on the polymer used in it to achieve desired formulation characteristics is an extremely challenging process. In the present research, predictive QSPR models were developed by correlating the physicochemical properties of varying grades of cellulose ethers (hydroxypropyl methylcellulose, HPMC) with those of nateglinide (NTG) containing tablets (in vitro and in vivo properties). Sustained release tablets of NTG were prepared by using different grades and concentrations of HPMC and subsequently characterized for in vitro as well as in vivo parameters. Further, QSPR models for individual formulation property were developed by correlating the polymeric physicochemical properties with the formulation characteristics. Subsequently, a true external validation method was used to validate the predictability of developed models. The dissolution study indicated Korsmeyer-Peppas as the best fit model following non-Fickian as drug transport mechanism extending the drug release up to 12 h. In vivo studies showed limited absorption of the NTG. Developed QSPR models showed promising validated predictability for formulation characteristics. The applicability of present work in formulation development could significantly reduce the time and cost expenditure on design trials without actually formulating a delivery system.

Quantitative Structure-Property Relationship Approach in Formulation Development: an Overview.

Chemoinformatics is emerging as a new trend to set drug discovery which correlates the relationship between structure and biological functions. The main aim of chemoinformatics refers to analyzing the similarity among molecules, searching the molecules in the structural database, finding potential drug molecule and their property. One of the key fields in chemoinformatics is quantitative structure-property relationship (QSPR), which is an alternative process to predict the various physicochemical and biopharmaceutical properties. This methodology expresses molecules via various numerical values or properties (descriptors), which encodes the structural characteristics of molecules and further used to calculate physicochemical properties of the molecule. The established QSPR model could be used to predict the properties of compounds that have been measured or even have been unknown, which ultimately accelerates the development process of a new molecule or the product. The formulation characteristics (drug release, transportability, bioavailability) can be predicted with the integration of QSPR approach. Therefore, QSPR modeling is an emerging trend to skip conventional drug as well as formulation development process. The current review highlights the overall process involved in the application of the QSPR approach in formulation development.

Medical evacuation on high seas.

A previously healthy Indian male seafarer aged 34 years, presented with vague perianal symptoms to the Master on a Very Large Crude Carrier (VLCC) in the Pacific Ocean. Over a few days, his condition deteriorated, and the company's medical consultant ashore, based on telephonic consultation, transmitted information and photos, diagnosed the condition as a life threatening case of Fournier's gangrene. The ship was then almost 1140 nm from the port. The consultant instructed the Master to intensify antibiotic treatment and started necessary procedures for an urgent complex medevac. Arranged by the United States Coast Guard, it involved deployment of two helicopters, two fixed wing aircrafts and an air tanker. Helicopters needed to be refuelled mid-air to increase their range of operations. Rendezvous point was 478 nm from Santa Barbara, California. 3½ hours after lift off from the vessel, the helicopter landed at Santa Barbara airport and the patient was transported to hospital. State-of-the-art treatment ashore preserved both testicles and after long term recovery the seafarer was again fit for ship duty.

Evaluation of Heat Stress in Construction Site of Metro Rail in Chennai.

INTRODUCTION: Tunnel boring machine (TBM) is used for constructing a tunnel. Worn out cutting tools have to be changed under difficult working conditions. Temperature is high and the work is strenuous. Work is often carried out under increased atmospheric pressure to ward off water ingress. Workers are at a very high risk. AIM: To evaluate heat stress during hyperbaric intervention on TBM during Chennai Metro Rail construction. METHODOLOGY: One hundred and eighty-eight miners after a thorough medical examination worked under increased atmospheric pressure for more than 45,000 man hours. Mitigating actions to protect workers by reducing temperature and increasing ventilation. Medical monitoring was done to identify and treat potential victims. RESULTS: 52° C was the highest temperature recorded. Most times work was carried out at a temperature range of 34-45° C. CONCLUSIONS: Motivations of monetary gains, reduced working hours, and food supplements played a major role in work execution without any untoward incidence.

Multifunctional Photostable Nanocomplex of ZnO Quantum Dots and Avobenzone via the Promotion of Enolate Tautomer.

Ideal multifunctional ultraviolet radiation (UVR) absorbents with excellent photostability, high molar absorptivity, broadband UVR screening, and desired skin sensorial properties remain a significant challenge for the sunscreen industry. The potential of the nanocomplex (NCx) formed by microwave synthesis of ZnO quantum dots (QDs) in the presence of Avobenzone (Av) for achieving these goals is reported. The NCx exhibits unique synergy between ZnO QD and Av components, which enhances the photostability and molar absorptivity, extends UVA filtering range, and provides a visible emission that matches the typical human in vivo skin emission color. Density functional theory (DFT) and time-dependent DFT calculations of ZnO-Av hybrid structures and comparison of their spectroscopic features with experiments suggest that ZnO QDs catalyze the formation of highly photostable surface enolate species via aldol condensation reaction. The combination of experiments and computations used in this study can advance the science and technology of photoprotection.

Neutralizing Antibody Response and Efficacy of Novel Recombinant Tetravalent Dengue DNA Vaccine Comprising Envelope Domain III in Mice.

BACKGROUND: Dengue is a global arboviral threat to humans; causing 390 million infections per year. The availability of safe and effective tetravalent dengue vaccine is a global requirement to prevent epidemics, morbidity, and mortality associated with it. METHODS: Five experimental groups (6 mice per group) each of 5-week-old BALB/c mice were immunized with vaccine and placebo (empty plasmid) (100 µg, i.m.) on days 0, 14 and 28. Among these, four groups (one group per serotype) of each were subsequently challenged 3 weeks after the last boost with dengue virus (DENV) serotypes 1-4 (100 LD50, 20 µl intracerebrally) to determine vaccine efficacy. The fifth group of each was used as a control. The PBS immunized group was used as mock control. Serum samples were collected before and after subsequent immunizations. EDIII fusion protein expression was determined by Western blot. Total protein concentration was measured by Bradford assay. Neutralizing antibodies were assessed by TCID50-CPE inhibition assay. Statistical analysis was performed using Stata/IC 10.1 software for Windows. One-way repeated measures ANOVA and Mann-Whitney test were used for neutralizing antibody analysis and vaccine efficacy, respectively. RESULTS: The recombinant EDIII fusion protein was expressed adequately in transfected 293T cells. Total protein concentration was almost 3 times more than the control. Vaccine candidate induced neutralizing antibodies against all four DENV serotypes with a notable increase after subsequent boosters. Vaccine efficacy was 83.3% (DENV-1, -3, -4) and 50% (DENV-2). CONCLUSION: Our results suggest that vaccine is immunogenic and protective; however, further studies are required to improve the immunogenicity particularly against DENV-2.

Protective effect of Tritone (Livosone) on oxidative DNA damage and its hepatoprotective potential against various hepatotoxic agent in wistar rats.

AIM: To evaluate antioxidant activity, DNA damage inhibition and hepatoprotecitve potential of polyherbal formulation Tritone (Livosone). METHODS: In vitro antioxidant activity of Tritone formulation was performed by using DPPH assay. Hepatoprotecitve potential of Tritone was evaluated against various hepatotoxic agents including Paracetamol (2g/kg b. wt p.o. single dose on 15th day), Galactosamine (400mg/kg b. wt. i.p. single dose on 8th day) and Alcohol (30% p.o.1ml/100g of rat for 15days). Tritone formulation at the doses of (40.5, 81 and 162mg/kg) and standard silymarin (100mg/kg) and Liv52 (270mg/kg) were administered p.o. The hepatoprotective assessment was done by estimating biochemical parameters: SGOT, SGPT, ALP and Total Bilirubin total protein and ChE levels. Additionally histopathological and DNA fragmentation study of Tritone was also performed. RESULT: Administration of hepatotoxins (paracetamol, D-GaiN and alcohol) in experimental animals showed significant biochemical, histological deterioration and DNA fragmentation. Pretreatment with Tritone (Livosone) shows significant reduction in serum SGOT, SGPT, ALP and total bilirubin levels and shows significant elevation in total protein and cholinesterase (ChE) levels compared to groups treated with hepatotoxic agents. Histopathological observations of rat liver pretreated with Tritone (Livosone) shows significant protection against hepatic damage. Inhibition of DNA fragmentation by Tritone indicates protective effect of formulation on liver at molecular level. Finally all the results were compared with standard drugs Silymarin and Liv52. CONCLUSION: Correlation of antioxidant activity, biochemical results, histopathological changes and inhibition of DNA damage after treatment with Tritone shows maximum hepatoprotective potential at dose 81mg/kg and 162mg/kg.

Compressed Air Working in Chennai During Metro Tunnel Construction: Occupational Health Problems.

Chennai metropolis has been growing rapidly. Need was felt of a metro rail system. Two corridors were planned. Corridor 1, of 23 km starting from Washermanpet to Airport. 14.3 km of this would be underground. Corridor 2, of 22 km starting from Chennai Central Railway station to St. Thomas Mount. 9.7 km of this would be underground. Occupational health centre's role involved selection of miners and assessing their fitness to work under compressed air. Planning and execution of compression and decompression, health monitoring and treatment of compression related illnesses. More than thirty five thousand man hours of work was carried out under compressed air pressure ranged from 1.2 to 1.9 bar absolute. There were only three cases of pain only ( Type I) decompression sickness which were treated with recompression. Vigilant medical supervision, experienced lock operators and reduced working hours under pressure because of inclement environmental conditions viz. high temperature and humidity, has helped achieve this low incident. Tunnelling activity will increase in India as more cities will soon opt for underground metro railway. Indian standard IS 4138 - 1977 " Safety code for working in compressed air" needs to be updated urgently keeping pace with modern working methods.

Novel Cream Containing Microsponges of Anti-Acne Agent: Formulation Development and Evaluation.

The rationale behind present work was to formulate a novel cream containing microsponges of miconazole nitrate to provide prolonged release. By means of quasi-emulsion solvent diffusion method using Eudragit RS-100 with different drug-polymer ratios microsponges were prepared. In the direction of optimizing microsponge formulation, diverse factors that affect microparticles physical properties were also investigated. Microsponges were characterized by SEM, DSC, FT-IR and particle size analysis, and also evaluated for morphology, drug loading and in vitro drug release. The drug polymer ratio reflected notable effect on drug content, encapsulation efficiency and particle size. It has been found that there was no chemical interaction between drug and polymers used as revealed by FT-IR and DSC spectra. SEM micrographs exposed that microsponges were spherical, with porous surface and have had 26.23 µm mean particle size. The microsponges were then incorporated in cream; which showed viscous modulus along with pseudoplastic behavior. In vitro drug release results depicted that microsponge with drug-polymer ratio of 1:2 was more efficient to give extended drug release of 78.28% at the end of 8 h; while conventional formulations get exhausted incredibly earlier by releasing 83.09% drug at the end of 4 h only. Thus the formulated cream containing microsponges of miconazole nitrate would be a promising alternative as compared to conventional therapy for secure and efficient treatment of acne and other topical infections.