Efficacy of dopamine, epinephrine and blood transfusion for treatment of fluid refractory shock in children with severe acute malnutrition or severe underweight and cholera or other dehydrating diarrhoeas: protocol for a randomised controlled clinical trial.

INTRODUCTION: Diarrhoea is one of the leading causes of under-5 childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. In severely malnourished children, diarrhoea progresses to shock, where the risk of mortality is even higher. At icddr,b Dhaka Hospital, the fatality rate is as high as 69% in children with severe malnutrition and fluid refractory septic shock. To date, no study has evaluated systematically the effects of inotrope or vasopressor or blood transfusion in children with dehydrating diarrhoea (eg, in cholera) and severe acute malnutrition (SAM) or severe underweight who are in shock and unresponsive to WHO-recommended fluid therapy. To reduce the mortality of severely malnourished children presenting with diarrhoea and fluid refractory shock, we aim to compare the efficacy of blood transfusion, dopamine and epinephrine in fluid refractory shock in children who do not respond to WHO-recommended fluid resuscitation. METHODS AND ANALYSIS: In this randomised, three-arm, controlled, non-masked clinical trial in children 1-59 months old with SAM or severe underweight and fluid refractory shock, we will compare the efficacy of dopamine or epinephrine administration versus blood transfusion in children who failed to respond to WHO-recommended fluid resuscitation. The primary outcome variable is the case fatality rate. The effect of the intervention will be assessed by performing an intention-to-treat analysis. Recruitment and data collection began in July 2021 and are now ongoing. Results are expected by May 2023. ETHICS AND DISSEMINATION: This study has been approved by the icddr,b Institutional Review Board. We adhere to the 'Declaration of Helsinki' (2000), guidelines for Good Clinical Practice. Before enrolment, we collect signed informed consent from the parents or caregivers of the children. We will publish the results in a peer-reviewed journal and will arrange a dissemination seminar. TRIAL REGISTRATION NUMBER: NCT04750070.

Digital Gangrene: An Unusual Manifestation of Non-Hodgkin Lymphoma.

Background: Non-Hodgkin lymphomas (NHLs) comprise a group of haematologic malignancies with different histologic subtypes. The clinical picture varies from indolent to aggressive presentation and nodal (lymphadenopathy) to extranodal (central nervous system, gastrointestinal, cutaneous plaque, or ulcer) involvement. Digital gangrene is seldom reported. Here, we describe a patient with pain and blackening of all fingers and toes as presenting symptoms of NHL. Case Presentation. A 32-year-old male weaver had been smoking three to five cannabis-containing cigarettes daily for about ten years and methamphetamine four to five tablets daily for five years. He had no history of Raynaud's phenomenon, fever, cough, weight loss, skin rash, joint pain, and atherogenic or thrombogenic risk factors. We found normal blood pressure and absent peripheral pulses in arms and legs, dry gangrene of all fingers and toes, generalized lymphadenopathy, and hepatomegaly with ascites. The chest X-ray was normal, as were blood sugar, lipid profile, and hepatic and renal function. Rheumatoid factor, antinuclear and antiphospholipid antibodies, C-ANCA and P-ANCA, hepatitis B and C, and HIV were negative. CT abdomen revealed hepatosplenomegaly with multiple intra-abdominal lymphadenopathies. The peripheral angiogram showed 90-99% stenosis of radial and dorsalis pedis arteries with normal proximal vessels. Diagnosis of non-Hodgkin lymphoma was confirmed by histopathology of cervical lymph node (diffuse type), immunohistochemically subtyped as peripheral T cell lymphoma (not otherwise specified). The digital ischemia worsened despite cessation of cannabis and methamphetamine and starting CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) treatment, making amputation necessary. Conclusion: We present, to our knowledge, the first report of peripheral T cell lymphoma, NOS presenting with gangrene in all digits complicated by methamphetamine and cannabis abuse. This uncommon vascular manifestation of non-Hodgkin lymphoma may cause a diagnostic dilemma and delayed initiation of treatment.

Nanophotonics based label free detection mechanism for real-time monitoring of interleukin-6.

Magneto-photonic crystals/MPCs are promising candidates for devising high-fidelity embedded biosensor systems which offer facile & real time detection of diagnostic proteins. Despite extensive use of magnetic nanomaterials for theranostic applications, the idea of exploiting its photonic response when assembled as a colloid inside a matrix remains unexplored. Herein, we report a novel label free method for quantitative detection of interleukin 6 which is a widely used prognostic marker for multiple pathological conditions. Cobalt ferrite/CoF and magnetite nanoparticles with Ms of 74.8 and 77 emu g-1 were assembled inside a hydrogel matrix with the application of an external magnetic field. Through the use of click chemistry, detecting antibodies were immobilized on their surface. The interaction of interleukin 6 with the antibodies produces a blue-shift in resonant wavelength and the reflectance intensity increases up to 50% and 44% when tested with CoF & magnetite based MPC respectively at a concentration of 50 pg ml-1. The dynamic range of the sensor lies within the prognostic values of IL-6, and the integrated sensing mechanism proposed in this study provides an ideal platform for real-time management of sepsis in patients with higher degree burns.

Recent Advances in Electrochemical and Optical Biosensors Designed for Detection of Interleukin 6.

Interleukin 6 (IL-6), being a major component of homeostasis, immunomodulation, and hematopoiesis, manifests multiple pathological conditions when upregulated in response to viral, microbial, carcinogenic, or autoimmune stimuli. High fidelity immunosensors offer real-time monitoring of IL-6 and facilitate early prognosis of life-threatening diseases. Different approaches to augment robustness and enhance overall performance of biosensors have been demonstrated over the past few years. Electrochemical- and fluorescence-based detection methods with integrated electronics have been subjects of intensive research due to their ability to offer a better signal-to-noise ratio, high specificity, ultra-sensitivity, and wide dynamic range. In this review, the pleiotropic role of IL-6 and its clinical significance is discussed in detail, followed by detection schemes devised so far for their quantitative analysis. A critical review on underlying signal amplification strategies and performance of electrochemical and optical biosensors is presented. In conclusion, we discuss the reliability and feasibility of the proposed detection technologies for commercial applications.

Anticancer and antibacterial potential of Rhus punjabensis and CuO nanoparticles.

The present study reports ecofriendly synthesis of CuO nanoparticles (NPs) using an extract of Rhus punjabensis as a reducing agent. NPs structural and composition analysis are evaluated by X-rays diffraction (XRD), Fourier transform infrared, Energy dispersive spectroscopy, Scanning electron microscopy, Transmission electron microscopy, and Thermal analysis. The NPs have pure single phase monoclinic geometry with spherical structure and high stability toward heat and with average particle size of about 36.6 and 31.27 nm calculated by XRD and SEM, respectively. NPs are tested for antibacterial, protein kinase (PK) inhibition, SRB cytotoxic, and NF-κB activities. Antibacterial activity is observed against B. subtilis and E. coli. Significant PK and SRB cytotoxic activity is observed with some NF-κB inhibition. NPs IC50 values against HL-60 and PC-3 prostate cancer cells are 1.82 ± 1.22 and 19.25 ± 1.55 µg/mL. The results encourage further studies for antibacterial and anticancer drug development of NPs using animal models.

Total Synthesis of Marine Natural Products Serinolamide A and Columbamide D.

In this report, an expeditious synthesis of two new biologically active marine natural products serinolamide A and columbamide D is documented. This convergent approach involves the key steps such as hydrolytic kinetic resolution, cross metathesis, Grignard reaction, Johnson-Claisen rearrangement, Mitsunobu, and so forth. Both of the target molecules were obtained from a common precursor (R)-7 with high enantioselectivity, less synthetic steps, and in good overall yields (serinolamide A 66% and columbamide D 62%).

A review on recent advances in chitosan based composite for hemostatic dressings.

High mortality rate in potentially survivable casualties due to severe hemorrhage is a major challenge in today's battlefield because technological advancements have revolutionized the combat tactics and complicated the type and severity associated with wound grades. Quality of pre-hospital care prior to patient evacuation is crucial in determining the survival rate in injured patients. To deal with this challenge, considerable improvements in the hemostatic dressings have been introduced and pre-hospital care has been upgraded in many tactical combat casually care guidelines. Combat Gauze has been widely used bandage which is now been replaced by different chitosan based hemostatic dressings. It not only exhibits anti-bacterial activity but also induces hemostasis via direct interaction with erythrocytes and platelets. Its hemostasis mechanism is not dependent on host coagulation pathway which makes it an ideal dressing to stop bleeding in coagulopathic patients. Different generations of chitosan bandages have been developed to overcome the limitations of previous ones. This review provides performance analysis of chitosan bandage generations and discusses the progress made in its fabrication methods during the recent years.

Development of self-nanoemulsifying tablet (SNET) for bioavailability enhancement of sertraline

The purpose of the study was to combine the advantages of self-nanoemulsifying drug delivery systems and tablets as a conventional dosage form. Self-nanoemulsifying drug delivery system (SNEDDS) was prepared to enhance the solubility and thus oral bioavailability of sertraline. Aqueous titration method was used to prepare the liquid SNEDDS; ternary phase diagrams were constructed and based on smaller droplet size (24.8 nm), minimum viscosity (153.63 cP) and polydispersity index (0.182), higher percentage transmittance (95%) and in vitro drug release (97%), an optimum system was designated. Liquid SNEDDS was transformed into free-flowing powder by solid adsorption technique followed by compression into tablets. In vitro release of sertraline from liquid and solid SNEDDS was found to be highly significant compared to plain sertraline (p<0.01). Pharmacokinetic studies after oral administration of liquid and solid SNEDDS in rats showed about 6-and 5-fold increased absorption of sertraline compared to the aqueous suspension of sertraline. These studies demonstrate that the solid SNEDDS are promising strategies for successful delivery of poorly water-soluble drug like sertraline

Regioselective 6-endo-dig iodocyclization: an accessible approach for iodo-benzo[a]phenazines.

A facile approach for the synthesis of substituted iodo-benzo[a]phenazines from 2-aryl-3-(aryl/alkylethynyl)quinoxalines via 6-endo-dig ring closure has been described under mild reaction conditions. Iodocyclization proceeds through the iodonium ion intermediate followed by nucleophilic cyclization with the C-H bond of the arene. Furthermore, the resulting 6-iodo-5-aryl/alkyl benzo[a]phenazine derivatives allowed for structural diversification by employing various coupling reactions. The structure of iodo-benzo[a]phenazine was confirmed by X-ray crystallographic studies of the compound.

Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications.

The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60±20nm. Various concentrations of HA ranging from 1 to 30wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA≤10wt% in TOPAS and at higher concentrations >10wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3MPa and 185% from 0.26 to 0.74MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications.

Self-emulsifying Pellets Prepared by Extrusion/Spheronization: In vitro/In vivo Evaluation.

AIMS: The purpose of the current study was to investigate the feasibility of producing solid self-emulsifying pellets using the extrusion/spheronization technique with an aim to increase the bioavailability of selected drug and also to encounter the problems associated with liquid lipid formulations. Selfemulsifying formulations are experiencing a very active development as reflected by the numerous publications and patents being granted on these systems. The patents on self-emulsifying formulation (US20036630150) and (US20006054136) helped in selecting the drug and excipients. MATERIAL AND METHODS: These pellets were prepared using liquid SNEDDS (24.59 % LBF M 2125 CS + Maisine35-1; 1:1 ratio) (oil), 50.27 % Labrasol (surfactant) and 25.13% Lauroglycol 90 (cosurfactant), adsorbent (silicon dioxide), pellet forming excipient (microcrystalline cellulose), binder (pregelatinized starch), disintegrant (croscarmelose sodium) and lubricant (corn starch). RESULTS: The resulting self-emulsified pellets loaded with about 32% liquid SNEDDS exhibited uniform pellet size and round shape, droplet size distribution following self-emulsification was nearly same to the liquid SNEDDS (26.5 nm and 24.8 nm, respectively). The in vitro release was significantly higher than the plain drug (p<0.01). AUC0-36h of sertraline from the pellets showed about 5-fold greater than the plain drug and no significant difference compared with the liquid SNEDDS (p>0.05). CONCLUSION: In conclusion, spherical pellets with low friability and self-emulsifying properties can be produced by the standard extrusion/spheronization technique. The pellets are capable of transferring lipophilic compounds into the aqueous phase and have a high potential to increase the oral absorption of lipophilic drugs.

Palladium-Catalyzed Intramolecular Fujiwara-Hydroarylation: Synthesis of Benzo[a]phenazines Derivatives.

An atom-economical Pd-catalyzed approach for the synthesis of benzophenazine derivatives using substituted 2-aryl-3-(aryl/alkylethynyl) quinoxaline in the presence of trifluoroacetic acid at 65 °C has been described. The chemistry involves in situ generation of cationic Pd(II) species, which functionalized the aromatic C-H bonds via electrophilic metalation followed by concomitant intramolecular trans-insertion of C-C triple bond to aryl-Pd complex. The results were supported by various control experiments including with electron-deficient arenes and deuterium labeling studies. The deuterium labeling studies supports electrophilic palladation of aromatic C-H over activation of C-C triple bond of alkyne. The structure of synthesized compounds was further confirmed by X-ray crystallography studies. This catalytic protocol has been efficiently applied for novel synthesis of highly functionalized benzo fused phenazines.

A critical review of algal biomass: A versatile platform of bio-based polyesters from renewable resources.

Algal biomass is an excellent renewable resource for the production of polymers and other products due to their higher growth rate, high photosynthetic efficiency, great potential for carbon dioxide fixation, low percentage of lignin and high amount of carbohydrates. Algae contain unique metabolites which are transformed into monomers suitable for development of novel polyesters. This review article mainly focuses on algal bio-refinery concept for polyester synthesis and on exploitation of algae-based biodegradable polyester blends and composites in tissue engineering and controlled drug delivery system. Algae-derived hybrid polyester scaffolds are extensively used for bone, cartilage, cardiac and nerve tissue regeneration due to their biocompatibility and tunable biodegradability. Microcapsules and microspheres of algae-derived polyesters have been used for controlled and continuous release of several pharmaceutical agents and macromolecules to produce humoral and cellular immunity with efficient intracellular delivery.

Recent developments and future prospects on bio-based polyesters derived from renewable resources: A review.

A significantly growing interest is to design a new strategy for development of bio-polyesters from renewable resources due to limited fossil fuel reserves, rise of petrochemicals price and emission of green house gasses. Therefore, this review aims to present an overview on synthesis of biocompatible, biodegradable and cost effective polyesters from biomass and their prospective in different fields including packaging, coating, tissue engineering, drug delivery system and many more. Isosorbide, 2,4:3,5-di-O-methylene-d-mannitol, bicyclic diacetalyzed galactaric acid, 2,5-furandicarboxylic acid, citric, 2,3-O-methylene l-threitol, dimethyl 2,3-O-methylene l-threarate, betulin, dihydrocarvone, decalactone, pimaric acid, ricinoleic acid and sebacic acid, are some important monomers derived from biomass which are used for bio-based polyester manufacturing, consequently, replacing the petrochemical based polyesters. The last part of this review highlights some recent advances in polyester blends and composites in order to improve their properties for exceptional biomedical applications i.e. skin tissue engineering, guided bone regeneration, bone healing process, wound healing and wound acceleration.

Synthesis of nano-hydroxyapatite and its rapid mediated surface functionalization by silane coupling agent.

In this work, hydroxyapatite (HA) nanorods were synthesized by simple one step wet precipitation method followed by their rapid surface functionalization via aminopropyltriethoxysilane (APTS) to give modified (HA-APTS) product. Functionalized hydroxyapatite (HA-APTS) holds amino groups on their surface that can be further functionalized with other bioactive molecules. The extent of functionalization of HA was studied under three different processing conditions; at room temperature, at 80 °C and under microwave condition (600 W). Three different temperatures have been use for the purpose of comparison between the functionalized products so that we can judge that whether there is any effect of temperature on the final products. In the last we conclude that temperature has no effect. So microwave condition is best to carried out the functionalization in just 5 min.

A new enantioselective synthesis of the anticonvulsant drug pregabalin (Lyrica) based on a hydrolytic kinetic resolution method.

A practical and efficient enantioselective synthesis of the anticonvulsant drug pregabalin is described for the first time using Jacobsen's hydrolytic kinetic resolution of a terminal epoxide as a key step and a source of chirality.

Chitin based polyurethanes using hydroxyl terminated polybutadiene, Part II: morphological studies.

Chitin-hydroxyl terminated polybutadiene (HTPB) based polyurethane (PU) was prepared and structure of the pre-designed PU was confirmed using FT-IR spectrometer. The FT-IR analysis confirmed that the crosslinking density increased with increasing the chitin contents in the final PU. During the detailed FT-IR study, it was observed that tri-functional character of chitin is responsible for the formation of network structure. The scanning electron microscope (SEM) analysis also confirmed the cross-linked structure of the material. The amount of carbon, nitrogen and oxygen elements obtained from EDX-SEM microanalysis also supported the results. The resistance in solubility against the solvent also confirmed the crosslinking behavior of the prepared polyurethane.

A new approach to construct a fused 2-ylidene chromene ring: highly regioselective synthesis of novel chromeno quinoxalines.

Regioselective construction of a fused 2-ylidene chromene ring was achieved for the first time by using AlCl(3)-induced C-C bond formation followed by Pd/C-Cu mediate coupling-cyclization strategy. A number of chromeno[4,3-b]quinoxaline derivatives were prepared by using this strategy. Single crystal X-ray diffraction study of a representative compound e.g. 6-(2,2-dimethylpropylidene)-4-methyl-6H-chromeno[4,3-b]quinoxalin-3-ol confirmed the presence of an exocyclic C-C double bond with Z-geometry. The crystal structure analysis and hydrogen bonding patterns of the same compound along with its structure elaboration via propargylation followed by Sonogashira coupling of the resulting terminal alkyne is presented. A probable mechanism for the formation of 2-ylidene chromene ring is discussed. Some of the compounds synthesized showed anticancer properties when tested in vitro.