Awareness raising and dealing with methanol poisoning based on effective strategies.

Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5-4 h after ingestion. After ingestion, methanol concentrations in the blood that are greater than 50 mg/dl should raise some concern. Ingested methanol is typically digested by alcohol dehydrogenase (ADH), and it is subsequently redistributed to the body's water to attain a volume distribution that is about equivalent to 0.77 L/kg. Moreover, it is removed from the body as its natural, unchanged parent molecules. Due to the fact that methanol poisoning is relatively uncommon but frequently involves a large number of victims at the same time, this type of incident occupies a special position in the field of clinical toxicology. The beginning of the COVID-19 pandemic has resulted in an increase in erroneous assumptions regarding the preventative capability of methanol in comparison to viral infection. More than 1000 Iranians fell ill, and more than 300 of them passed away in March of this year after they consumed methanol in the expectation that it would protect them from a new coronavirus. The Atlanta epidemic, which involved 323 individuals and resulted in the deaths of 41, is one example of mass poisoning. Another example is the Kristiansand outbreak, which involved 70 people and resulted in the deaths of three. In 2003, the AAPCC received reports of more than one thousand pediatric exposures. Since methanol poisoning is associated with high mortality rates, it is vital that the condition be addressed seriously and managed as quickly as feasible. The objective of this review was to raise awareness about the mechanism and metabolism of methanol toxicity, the introduction of therapeutic interventions such as gastrointestinal decontamination and methanol metabolism inhibition, the correction of metabolic disturbances, and the establishment of novel diagnostic/screening nanoparticle-based strategies for methanol poisoning such as the discovery of ADH inhibitors as well as the detection of the adulteration of alcoholic drinks by nanoparticles in order to prevent methanol poisoning. In conclusion, increasing warnings and knowledge about clinical manifestations, medical interventions, and novel strategies for methanol poisoning probably results in a decrease in the death load.

A comparison between ß-tricalcium phosphate and chitosan poly-caprolactone-based 3D melt extruded composite scaffolds.

Melt extrusion 3D printing has become an attractive additive manufacturing technology to construct degradable scaffolds as tissue precursors in order to create clinically relevant medical devices. Towards this end, a commonly used synthetic polyester, poly-caprolactone (PCL), was used to make scaffolds composed of different biomaterial compositions to increase bioactivity using 3D melt pneumatic extrusion technology. Varying ratios of the natural biopolymer, chitosan, or the bioceramic, ß-tricalcium phosphate (TCP) were blended with PCL to fabricate support scaffolds with three-dimensional (3D) architecture for human bone-marrow derived mesenchymal stem cell (hBMSC) growth for potential bone regeneration application. In this study, basic printing requirements as well as biomaterial dynamic mechanical (DMA), elemental, and thermogravimetric (TGA) analysis results demonstrate material homogeneity as well as thermal stability. Scaffold morphology and microarchitecture were assessed using scanning electron microscopy (SEM) alongside in vitro scaffold degradation and biological characterisation. Human BMSC proliferation was assessed using fluorescence imaging, and quantitated via the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. These in vitro cell viability studies revealed that the highest chitosan concentration blend of 20% favoured the most hBMSC growth, exhibited the most swelling, and showed minimal degradation after 28 days. The 20% TCP blend had the second highest hBMSC growth, exhibited moderate swelling, and the fastest degradation rate. Overall, this study demonstrates the first direct comparison of a natural biopolymer-based, that is, chitosan, 3D melt extruded PCL composite with that of a bioceramic-based, that is, ß-TCP, PCL composite and their effects on hBMSC 3D proliferation. 3D melt extruded PCL-based composite scaffolds methodology offers a straightforward way to print scaffolds with good shape fidelity, interconnected porosities and enhanced bioactivity; and demonstrates their potential use for regenerative, bone repair applications.

Regional anesthesia in the coronavirus disease (COVID-19) pandemic: Clinical guidelines by AORA, India.

Anesthesiologists are amongst the front line warriors in this COVID-19 pandemic. We need to change our preferences and practices to reduce the spread to healthcare workers and patients in the hospital. General anesthesia involves aerosol-generating procedures while ventilating and intubating the patients. Regional anesthesia maintains respiratory functions, circumvents airway instrumentation and helps to limit viral transmission. This makes a strong case to patronize regional anaesthesia practises whenever possible. Due to various limitations of diagnostic tests available, all patients can be treated as COVID-19 positive and necessary precautions are suggested to limit the transmission. The importance of a practise advisory is to clear the mist around the dos and don'ts to ensure clarity of thoughts leading to improved safety of both patient and health care professional. We propose clinical guidelines for regional anaesthesia practices in COVID-19 positive patient posted for surgery. Furthermore, current recommendations on confirming the COVID-19 negative status is referred. These features are subject to change further with time.

Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl.

The Bcr-Abl tyrosine kinase oncogene causes chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We describe a novel selective inhibitor of Bcr-Abl, AMN107 (IC50 <30 nM), which is significantly more potent than imatinib, and active against a number of imatinib-resistant Bcr-Abl mutants. Crystallographic analysis of Abl-AMN107 complexes provides a structural explanation for the differential activity of AMN107 and imatinib against imatinib-resistant Bcr-Abl. Consistent with its in vitro and pharmacokinetic profile, AMN107 prolonged survival of mice injected with Bcr-Abl-transformed hematopoietic cell lines or primary marrow cells, and prolonged survival in imatinib-resistant CML mouse models. AMN107 is a promising new inhibitor for the therapy of CML and Ph+ ALL.

Integrating Fused Deposition Modeling and Melt Electrowriting for Engineering Branched Vasculature.

We demonstrate for the first time the combination of two additive manufacturing technologies used in tandem, fused deposition modelling (FDM) and melt electrowriting (MEW), to increase the range of possible MEW structures, with a focus on creating branched, hollow scaffolds for vascularization. First, computer-aided design (CAD) was used to design branched mold halves which were then used to FDM print conductive polylactic acid (cPLA) molds. Next, MEW was performed over the top of these FDM cPLA molds using polycaprolactone (PCL), an FDA-approved biomaterial. After the removal of the newly constructed MEW scaffolds from the FDM molds, complementary MEW scaffold halves were heat-melded together by placing the flat surfaces of each half onto a temperature-controlled platform, then pressing the heated halves together, and finally allowing them to cool to create branched, hollow constructs. This hybrid technique permitted the direct fabrication of hollow MEW structures that would otherwise not be possible to achieve using MEW alone. The scaffolds then underwent in vitro physical and biological testing. Specifically, dynamic mechanical analysis showed the scaffolds had an anisotropic stiffness of 1 MPa or 5 MPa, depending on the direction of the applied stress. After a month of incubation, normal human dermal fibroblasts (NHDFs) were seen growing on the scaffolds, which demonstrated that no deleterious effects were exerted by the MEW scaffolds constructed using FDM cPLA molds. The significant potential of our hybrid additive manufacturing approach to fabricate complex MEW scaffolds could be applied to a variety of tissue engineering applications, particularly in the field of vascularization.

Effect of Short Glass Fiber Addition on Flexural and Impact Behavior of 3D Printed Polymer Composites.

Fused deposition modeling (FDM), one of the most widely used additive manufacturing (AM) processes, is used for fabrication of 3D models from computer-aided design data using various materials for a wide scope of applications. The principle of FDM or, in general, AM plays an important role in minimizing the ill effects of manufacturing on the environment. Among the various available reinforcements, short glass fiber (SGF), one of the strong reinforcement materials available, is used as a reinforcement in the acrylonitrile butadiene styrene (ABS) matrix. At the outset, very limited research has been carried out till date in the analysis of the impact and flexural strength of the SGF-reinforced ABS polymer composite developed by the FDM process. In this regard, the present research investigates the impact and flexural strength of SGF-ABS polymer composites by the addition of 15 and 30 wt % SGF to ABS. The tests were conducted as per ASTM standards. Increments in flexural and impact properties were observed with the addition of SGF to ABS. The increment of 42% in impact strength was noted for the addition of 15 wt % SGF and 54% increase with the addition of 30 wt % SGF. On similar lines, flexural properties also showed improved values of 44 and 59% for the addition of 15 and 30 wt % SGF to ABS. SGF addition greatly enhanced the properties of flexural and impact strength and has paved the path for the exploration of varied values of reinforcement into the matrix.

Evaluating Critical Influencing Factors of Desalination by Membrane Distillation Process-Using Multi-Criteria Decision-Making.

Water desalination by membrane distillation (MD) can be affected by a wide range of operating parameters. The present work uses combinational approach of Analytical Hierarch process (AHP) and Fuzzy Analytical Hierarchy process (Fuzzy-AHP) to identify the most important parameters in the MD desalination. Five process parameters and key-performance indicators, named derivable outputs (DOs), are considered, along with the critical factors affecting these DOs in the current study. The DOs and the critical influencing factors (CIFs) are selected based on their experimental feasibility. The investigation involves five DOs, which are liquid entry pressure, thermal power consumption, permeate quality, permeate flux, and pumping (feed circulation) power. A total of twenty-five critical influencing factor were associated with the DOs. The identification of the DOs and CIFs was based on the literature review, and further analyses were performed. Both methods, AHP and Fuzzy-AHP, determined six extremely important CIFs in the desalination MD, which are feed temperature, feed concentration, or feed salinity; feed flow rate; membrane hydrophobicity; pore size; and membrane material. Moderately important CIFs are found to be four by both methods. These common CIFs are feed solution properties, membrane thickness, feed channel geometry, and pressure difference along the feed channel. Finally, the least preferred CIFs are four common in both methods that are MD configuration, duration of test, specific heat of feed solution, and viscosity.

Application of triazoles as bioisosteres and linkers in the development of microtubule targeting agents.

The triazole ring system has emerged as an exciting prospect in the optimization studies of promising lead molecules in the quest for new drugs for clinical usage. Several marketed drugs possess these versatile moieties that are used in a wide range of medical indications. This stems from the unique intrinsic properties of triazoles, which impart stability to the basic pharmacophoric unit with an added advantage of being a bioisostere of different chemical functionalities. In the last decade, the use of triazoles as bioisosteres and linkers in the development of microtubule targeting agents has been extensively investigated. The present review highlights the advances in this promising area of drug discovery and development.

Comparison of the patterns of antral follicular development between hormonally synchronized and natural estrous cycles of non-seasonal, polyestrous goats in the tropics.

The effects of estrus synchronization with prostaglandin F(2α) (PGF(2α)) and Controlled Internal Drug Release Device (CIDR) on ensuing antral follicular development were documented and compared to natural estrous cycles of non-seasonal tropical goats. Two to six follicular waves were observed, with the three-follicular wave pattern being most frequently observed (58%), followed by four follicular waves (31.6%) per estrous cycle. There were no significant differences (p>0.05) between the PGF(2α)- or CIDR-synchronized and natural estrous cycles nor between the synchronized and subsequent non-synchronized cycles in terms of the time of ovulation, the duration of inter-ovulatory intervals, daily numbers of antral follicles ≥3mm in diameter, and the number of follicular waves per cycle in the goats of the present study.