Real-World Assessment of Personalized Approach With Voglibose Fixed-Dose Combination in Type 2 Diabetes Mellitus.

BACKGROUND: Post-prandial hyperglycemia (PPHG) remains a complex aspect in the management of type 2 diabetes mellitus (T2DM) in the Indian population due to uncertainty in the optimal utilization of alpha-glucosidase inhibitors (AGIs) either as standalone therapy or in combination, whether initiated initially or as a sequential therapy. METHODS: This was a post-approval, observational, multicentric clinical study conducted at 50 centers according to principles of the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use Guideline for Good Clinical Practice (ICH-GCP) and Declaration of Helsinki and local ethics approval. Descriptive and analytical statistics were applied for conclusion and categorical variables using SPSS version 29.0.1.0 (171) (Armonk, NY: IBM Corp.). RESULTS: Protocol analyses of 515 cases revealed baseline demographics as follows: age 57.35±10.04 years, weight 72.86±10.92 kg, and BMI 28.33±6.07 kg/m2. Comorbidities included hypertension (N=169, 32.82%), thyroid disorders (N=99, 19.22%), and heart failure (N=92, 17.86%). Concomitant oral antidiabetics (OADs) prescribed as DPP4i (9.50%), SGLT2i (19.20%), and DPP4i+SGLT2i (7.20%). Study drug reduced glycosylated hemoglobin (HbA1c) by 13.77% (1.25% mean change, p<0.01), fasting blood glucose (FBG) by 23.69% (44.61 mg/dL mean change, p<0.01), post-prandial blood glucose (PPBG) by 24.57% (70.46 mg/dL mean change, p<0.01), and body weight by 4.43% (3.21 kg mean change, p<0.01) over 12 weeks. A total of 161 patients accomplished targeted PPBG of <180 mg/dL (119.13 mg/dL mean change, p<0.01). Regression analysis considering PPBG and HbA1c ≤7.5% showed a weak correlation between them (R-value=0.13, R-squared value=0.02), whereas between PPBG and HbA1c ≤9% yielded moderate positive correlation (R-value=0.53, R-squared value=0.28). There were no adverse events reported or analyzed during the observation period. CONCLUSION: Voglibose fixed-dose combination (FDC) demonstrates significant effectiveness at the initial dosage when started early in the management of T2DM and high PPBG levels. Moreover, it exhibits good tolerability, thereby contributing to higher compliance among Indian patients who consume a high-carbohydrate diet.

Investigating the phenology and interactions of competitive plant species co-occurring with invasive Lantana camara in Indian Himalayan Region.

Invasive plant species are considered one of the significant drivers of habitat loss, leading to biodiversity loss. They have also been observed to alter the local ecology, resulting in a decline of native flora. The management of invasive species is widely recognised as one of the most severe challenges to biodiversity conservation. The International Union for Conservation of Nature (IUCN) considers Lantana camara, as one of the ten worst weeds. Over time, native and indigenous species may evolve to co-exist or compete with invasive species, reducing invader fitness. It is observed that species competition fluctuates throughout environmental gradients, life phases, and abundances. Hence, competition outcome is very context-dependent. To address this challenge, we conducted a comprehensive study in three phases: we identified native species coexisting with Lantana in their natural habitats in the Doon Valley (Phase I) and documented the phenotypic traits of selected coexisting species using the Landmark BBCH (Biologische Bun-desantalt, Bundessortenamt und Chemische Industrie) scale, revealing the phenological growth patterns of selected co-existing species (Phase II). This was followed by conducting pot (Phase IIIa) and field (Phase IIIb) experiments to study the interactions between them. Notably, Justicia adhatoda, Broussonetia papyrifera, Pongamia pinnata, Urtica dioica and Bauhinia variegata demonstrated promising results in both pot and field conditions. Furthermore, after the mechanical removal of Lantana and prior to the plantation in the field experiments, four native grass species were introduced using the seed ball method. Among these, Pennisetum pedicellatum and Sorghum halpense exhibited prompt regeneration and effectively colonised the field, densely covering the cleared area. The study provides a comprehensive management plan for the restoration of Lantana affected areas through competition using native species. This study utilizes phenological assessment for native plant selection using reclamation from native grasses and proposes a management plan for combating invasive Lantana.

The Clostridium Metabolite P-Cresol Sulfate Relieves Inflammation of Primary Biliary Cholangitis by Regulating Kupffer Cells.

OBJECTIVE: To study the effect and mechanism of the Clostridium metabolite p-Cresol sulfate (PCS) in primary biliary cholangitis (PBC). METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to detect differences in tyrosine, phenylalanine, tryptophan, PCS, and p-Cresyl glucuronide (PCG) between the serum of PBC patients and healthy controls. In vivo experiments, mice were divided into the normal control, PBC group, and PBC tyrosine group. GC-MS was used to detect PCS and PCG. Serum and liver inflammatory factors were compared between groups along with the polarization of liver Kupffer cells. Additionally, PCS was cultured with normal bile duct epithelial cells and Kupffer cells, respectively. PCS-stimulated Kupffer cells were co-cultured with lipopolysaccharide-injured bile duct epithelial cells to detect changes in inflammatory factors. RESULTS: Levels of tyrosine and phenylalanine were increased, but PCS level was reduced in PBC patients, with PCG showing a lower concentration distribution in both groups. PCS in PBC mice was also lower than those in normal control mice. After oral administration of tyrosine feed to PBC mice, PCS increased, liver inflammatory factors were decreased, and anti-inflammatory factors were increased. Furthermore, Kupffer cells in the liver polarized form M1 transitioned to M2. PCS can damage normal bile duct epithelial cells and suppress the immune response of Kupffer cells. But PCS protects bile duct epithelial cells damaged by LPS through Kupffer cells. CONCLUSIONS: PCS produced by Clostridium-metabolized tyrosine reduced PBC inflammation, suggesting that intervention by food, or supplementation with PCS might represent an effective clinical strategy for treating PBC.

Biochar application for greenhouse gas mitigation, contaminants immobilization and soil fertility enhancement: A state-of-the-art review.

Rising global temperature, pollution load, and energy crises are serious problems, recently facing the world. Scientists around the world are ambitious to find eco-friendly and cost-effective routes for resolving these problems. Biochar has emerged as an agent for environmental remediation and has proven to be the effective sorbent to inorganic and organic pollutants in water and soil. Endowed with unique attributes such as porous structure, larger specific surface area (SSA), abundant surface functional groups, better cation exchange capacity (CEC), strong adsorption capacity, high environmental stability, embedded minerals, and micronutrients, biochar is presented as a promising material for environmental management, reduction in greenhouse gases (GHGs) emissions, soil management, and soil fertility enhancement. Therefore, the current review covers the influence of key factors (pyrolysis temperature, retention time, gas flow rate, and reactor design) on the production yield and property of biochar. Furthermore, this review emphasizes the diverse application of biochar such as waste management, construction material, adsorptive removal of petroleum and oil from aqueous media, immobilization of contaminants, carbon sequestration, and their role in climate change mitigation, soil conditioner, along with opportunities and challenges. Finally, this review discusses the evaluation of biochar standardization by different international agencies and their economic perspective.

Design and In-silico study of bioimaging fluorescence Graphene quantum dot-Bovine serum albumin complex synthesized by diimide-activated amidation.

Graphene quantum dot possesses advantageous characteristics like tunable fluorescence, nanometer size, low cytotoxicity, high biocompatibility enabling them as an ideal material for fluorescence bio-imaging. It exhibits a unique characteristic of DNA cleavage activity enhancer, gene/drug carrier, and anticancer targeting applications. In this article, we discussed the preparation of graphene quantum dot through the bottom-up method. Carbodiimide-activated amidation reactions were used for the functionalization of graphene quantum dot with Bovine Serum Albumin. Fluorescence spectroscopy data showed that the graphene quantum dot has size-dependent fluorescence emission. TEM and AFM studies showed that the size of graphene quantum dot was around 20 nm with narrow size distribution. Carbodiimide-activated amidation conjugation was successful in binding the protein onto graphene quantum dot and these conjugates were characterized by DLS, FTIR, fluorescence spectroscopy, and agarose gel electrophoresis. We also studied the structural-based in-silico molecular dynamic simulation by AutoDock, PyRx, and Discovery Studio Visualizer. Based on the virtual screening analysis and higher negative energy incorporation, it is observed that graphene quantum dot conjugated with bovine serum albumin quickly and formed is highly stable complex, which makes them a potential candidate for future applications in the field of bio-imaging, bio-sensing, gene/drug delivery, and tumor theragnostic.

Biclonal gammopathay in a case of severe COVID-19.

COVID-19 is a disease caused by a coronavirus named as SARS-CoV-2. It has become pandemic due to its contagious nature. Majority of the patients are asymptomatic or having mild flu like symptoms. Few need hospitalisation due to severe acute respiratory infection (SARI). Co-morbidity like diabetes, hypertension, renal failure etc. are associated with severe COVID-19 that often causes death. There have been only two published case reports of monoclonal gammopathy of unknown significance (MGUS) in patients with COVID-19 disease. Cytokine storm is often observed in severe COVID-19 and various cytokines including IL-6 that activates plasma cells are increased in blood in this condition. Here we present a case of severe COVID-19 patient with bioclonal gammopathy. He was known diabetic and hypertensive on treatment. He developed SARI, cytokines storm and septicaemia, treated with antibiotics, enoxaparin, hydroxychloroquine, insulin, anti-hypertensives, put on ventilator, subsequently developed septicaemia, multi-organ failure and died. Two M-bands on serum capillary electrophoresis with presence IgG-κ on both the M-bands indicates a biclonal gammopathy of unknown significance in this patient. We conclude that like MGUS, early stage biclonal gammopathy, although rare, gets manifested with M-bands on plasma protein electrophoresis. It is probably due to high level of IL-6 associated with cytokine storm in severe COVID-19 that stimulate early stage dyscratic plasma cells. Such biclonal gammopathy might be a risk factor for severe COVID-19 and associated mortality.

Kupffer Cells Regulate Natural Killer Cells Via the NK group 2, Member D (NKG2D)/Retinoic Acid Early Inducible-1 (RAE-1) Interaction and Cytokines in a Primary Biliary Cholangitis Mouse Model.

BACKGROUND Kupffer cells and natural killer (NK) cells has been identified as contributing factors in the pathogenesis of hepatitis, but the detailed mechanism of these cell types in the pathogenesis of primary biliary cholangitis (PBC) is poorly understood. MATERIAL AND METHODS In this study, polyinosinic: polycytidylic acid (poly I: C), 2-octynoic acid-bovine serum albumin (2OA-BSA) and Freund's adjuvant (FA) were injected to establish a murine PBC model, from which NK cells and Kupffer cells were extracted and isolated. The cells were then co-cultivated in a designed culture system, and then NK group 2, member D (NKG2D), retinoic acid early inducible-1 (RAE-1), F4/80, and cytokine expression levels were detected. RESULTS The results showed close crosstalk between Kupffer cells and NK cells. PBC mice showed increased surface RAE-1 protein expression and Kupffer cell cytokine secretion, which subsequently activated NK cell-mediated target cell killing via NKG2D/RAE-1 recognition, and increased inflammation. NK cell-derived interferon-γ (IFN-γ) and Kupffer cell-derived tumor necrosis factor alpha (TNF-alpha) were found to synergistically regulate inflammation. Moreover, interleukin (IL)-12 and IL-10 improved the crosstalk between NK cells and Kupffer cells. CONCLUSIONS Our findings in mice are the first to suggest the involvement of the NKG2D/RAE-1 interaction and cytokines in the synergistic effects of NK and Kupffer cells in PBC.

Concomitant methicillin-resistant Staphylococcus aureus infection in tubercular sacroiliitis masquerading as anti-tubercular drug resistance: Role for molecular diagnosis.

A 23-year-old female on anti-tubercular therapy for tuberculous sacroiliitis presented with right sided gluteal and thigh abscess. Suspecting treatment failure, surgical evacuation of purulent material was done. The bacteriological isolation showed positivity for methicillin-resistant Staphylococcus aureus. Although the microbiological and histopathology examination of the specimen were negative for tubercular isolates, the cartridge based -nucleic acid amplification tests revealed positive genes for Mycobacterium tuberculosis and additional primers showed sensitivity for rifampicin and isoniazid. She was adequately treated with vancomycin for six weeks and anti-tubercular drugs for eight months and followed till the bony ankyloses at 18 months. This is a rare case based scenario wherein concomitant staphylococcal infection in tubercular sacroiliitis masqueraded as anti-tubercular drug resistance. The cartridge-based nucleic acid amplification test for tuberculosis is a rapid and sensitive modality in identifying mycobacteria even mixed infections and also determine drug resistance. There are fewer consensuses in the literature regarding the drugs and duration of anti-tubercular regime for tuberculous sacroiliitis with most regimes using four drugs between six to eighteen months.

Palbociclib: A breakthrough in breast carcinoma in women.

Breast cancer (BC) is the most common cancer and leading cause of death in women worldwide. Cellular proliferation, growth, and division are tightly controlled by the cell-cycle regulatory machinery. An important pathway is cyclin-dependent kinases (CDKs) which regulate cell cycle and thus control transcriptional processes. In human cancer, multiple CDK family members are commonly deregulated. The cyclin D-CDK4/6-retinoblastoma (RB) protein-INK4 axis is particularly affected in many solid tumors which leads to cancer cell proliferation. This has led to long-standing interest in targeting CDK4/6 as an anticancer strategy. Different investigational agents that have been tested which inhibit multiple cell cycle and transcriptional CDKs but have carried excessive toxicity thus failed to stand the rational of human use. Amongst several selective and potent inhibitors of CDK4/6, palbociclib is the first to be accessed suitable for human use having explicit selectivity toward CDK4/6. Its mechanism is to arrest cells in G1 phase by blocking RB phosphorylation at CDK4/6-specfic sites without affecting the growth of cells which are RB-deficient. Studies conducted in patients of BC having cells with advanced RB-expression demonstrated acceptable side effects but dose-limiting toxicities primarily neutropenia and thrombocytopenia, with prolonged stable disease in patients.

Simple and sensitive electrochemical impedimetric approach towards analysis of biophysical interaction.

Study of biophysical interactions have been carried out using specific combination of proteins such as human IgG (as antigen) and anti-human IgG (as complementary antibody; raised in rabbit). Bovine serum albumin (BSA) was used to block any nonspecific interaction between antigen and antibody as BSA has been reported to bind to several sites non-specifically. Optimization of BSA concentration was done in order to make the antigen-antibody interaction relatively more pronounced and specific. We have used gold electrode in order to provide a relatively inert platform for adsorption/immobilization of protein molecules. The interaction between the antigen and antibody caused an increase in the charge transfer resistance (parallel resistance in Randles cell model) for an indicator molecule (hexacyanoferrate) and this was monitored by impedance spectroscopy. Detection limit for the antigen was found to be about 50 ng/mL. The approach presented is general and versatile and can be used for any antigen-antibody pair without any significant modification.

Naloxegol: First oral peripherally acting mu opioid receptor antagonists for opioid-induced constipation.

Opioid-induced constipation (OIC) is one of the most troublesome and the most common effects of opioid use leading to deterioration in quality of life of the patients and also has potentially deleterious repercussions on adherence and compliance to opioid therapy. With the current guidelines advocating liberal use of opioids by physicians even for non-cancer chronic pain, the situation is further complicated as these individuals are not undergoing palliative care and hence there cannot be any justification to subject these patients to the severe constipation brought on by opioid therapy which is no less debilitating than the chronic pain. The aim in these patients is to prevent the opioid-induced constipation but at the same time allow the analgesic activity of opioids. Many drugs have been used with limited success but the most specific among them were the peripherally acting mu opioid receptor antagonists (PAMORA). Methylnaltrexone and alvimopan were the early drugs in this group but were not approved for oral use in OIC. However naloxegol, the latest PAMORA has been very recently approved as the first oral drug for OIC. This article gives an overview of OIC, its current management and more specifically the development and approval of naloxegol, including pharmacokinetics, details of various clinical trials, adverse effects and its current status for the management of OIC.

Tuberculous osteomyelitis of the maxilla: A rarest of rare case report.

Tuberculosis is a chronic granulomatous systemic infectious disease caused by Mycobacterium tuberculosis. The oral lesions found in tuberculosis are relatively rare and may present as ulcers, erythematous patches, indurated lesions, nodules or as bony jaw lesions. Oral tubercular lesions sometimes present a confusing clinical presentation and can be overlooked. Hence, we document a case of tuberculous osteomyelitis of the maxilla in a 19-year-old female patient, who was initially treated for multiple periodontal dental abscesses, which later proved to be tubercular osteomyelitis of the maxilla. Although it is a rare occurrence, the differential diagnosis of tuberculous osteomyelitis must always be considered when it fails to respond to routine therapy.

Temporoparietal fascia flap in intra-oral reconstruction without split thickness skin graft cover: a case report.

The temporoparietal fascia flap with its long rotational axis and extensive mobilisation properties, can provide vascularised tissue to repair the most distant areas in the orofacial region. The donor site morbidity is minimal with a well-concealed scar hidden in the hair-bearing scalp. However, the temporoparietal fascia flap is usually used together with a split thickness skin graft. This leads to one more donor site causing increased morbidity. In this case temporoparietal fascia flap was used for an intra-oral reconstruction in a case of oral submucous fibrosis, without a split thickness skin graft cover. The healing was excellent and the flap provided a good surface for remucosalisation.

Salmonella kingabwa meningitis in a neonate.

A 23-day-old male baby was admitted with 1 day history of high temperature, irritability and poor feeding. His general examination was unremarkable. Salmonella species grew from CSF culture and subsequent identification revealed Salmonella kingabwa, a serotype which rarely causes human illness. The child lived with his parents and regularly visited his grandmother for 4 h every day. Grandmother kept five snakes and five water dragons as pets. They lived in tanks and crawled freely around the house. For decades the reptiles have been known to carry Salmonella, which can be transmitted directly or indirectly to humans through ingestion of the bacteria, which causes subsequent infection. Reptile exposure is a rare but significant risk factor for Salmonella illness in England and contact with reptiles should be avoided by children less than 5 years old, pregnant ladies, older and those with impaired immunity.

Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications.

Magnetic nanoparticles with appropriate surface coatings are increasingly being used clinically for various biomedical applications, such as magnetic resonance imaging, hyperthermia, drug delivery, tissue repair, cell and tissue targeting and transfection. This is because of the nontoxicity and biocompatibility demand that mainly iron oxide-based materials are predominantly used, despite some attempts to develop 'more magnetic nanomaterials' based on cobalt, nickel, gadolinium and other compounds. For all these applications, the material used for surface coating of the magnetic particles must not only be nontoxic and biocompatible but also allow a targetable delivery with particle localization in a specific area. Magnetic nanoparticles can bind to drugs and an external magnetic field can be applied to trap them in the target site. By attaching the targeting molecules, such as proteins or antibodies, at particles surfaces, the latter may be directed to any cell, tissue or tumor in the body. In this review, different polymers/molecules that can be used for nanoparticle coating to stabilize the suspensions of magnetic nanoparticles under in vitro and in vivo situations are discussed. Some selected proteins/targeting ligands that could be used for derivatizing magnetic nanoparticles are also explored. We have reviewed the various biomedical applications with some of the most recent uses of magnetic nanoparticles for early detection of cancer, diabetes and atherosclerosis.

Bilateral adrenal abscess in a neonate.

A 23-day-old male baby with a history of perinatal hypoxia presented with refusal of feeds and abdominal distension. The child had a right-sided cystic upper abdominal mass and features of neonatal septicemia. Abdominal ultrasound (US) and contrast-enhanced CT scan showed bilateral adrenal abscesses. Laparotomy with drainage of the abscesses successfully treated the condition. The literature on the subject is reviewed.

Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications.

Superparamagnetic iron oxide nanoparticles (SPION) with appropriate surface chemistry have been widely used experimentally for numerous in vivo applications such as magnetic resonance imaging contrast enhancement, tissue repair, immunoassay, detoxification of biological fluids, hyperthermia, drug delivery and in cell separation, etc. All these biomedical and bioengineering applications require that these nanoparticles have high magnetization values and size smaller than 100 nm with overall narrow particle size distribution, so that the particles have uniform physical and chemical properties. In addition, these applications need special surface coating of the magnetic particles, which has to be not only non-toxic and biocompatible but also allow a targetable delivery with particle localization in a specific area. To this end, most work in this field has been done in improving the biocompatibility of the materials, but only a few scientific investigations and developments have been carried out in improving the quality of magnetic particles, their size distribution, their shape and surface in addition to characterizing them to get a protocol for the quality control of these particles. Nature of surface coatings and their subsequent geometric arrangement on the nanoparticles determine not only the overall size of the colloid but also play a significant role in biokinetics and biodistribution of nanoparticles in the body. The types of specific coating, or derivatization, for these nanoparticles depend on the end application and should be chosen by keeping a particular application in mind, whether it be aimed at inflammation response or anti-cancer agents. Magnetic nanoparticles can bind to drugs, proteins, enzymes, antibodies, or nucleotides and can be directed to an organ, tissue, or tumour using an external magnetic field or can be heated in alternating magnetic fields for use in hyperthermia. This review discusses the synthetic chemistry, fluid stabilization and surface modification of superparamagnetic iron oxide nanoparticles, as well as their use for above biomedical applications.

Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles.

The aim of this study was to modify the surfaces of superparamagnetic iron oxide nanoparticles (SPION) with pullulan in order to reduce the cytotoxicity and enhance the cellular uptake of the nanoparticles. In this study, we have prepared and characterised the pullulan coated superparamagnetic iron oxide nanoparticles (Pn-SPION) of size around 40-45 nm with magnetite inner core and hydrophilic outer shell of pullulan. We have investigated the effect of cellular uptake of uncoated and Pn-SPION on cell adhesion/viability, cytotoxicity, morphology and cytoskeleton organisation of human fibroblasts. Cell cytotoxicity/adhesion studies of SPIONs on human dermal fibroblasts showed that the particles are toxic and their internalisation resulted in disruption of cytoskeleton organisation of cells. On the other hand, Pn-SPIONs were found to be non-toxic and induced changes in cytoskeleton organisation different from that observed with SPION. Transmission electron microscopy results indicated that the SPION and Pn-SPION were internalised into cells via different mechanisms, thereby suggesting that the particle endocytosis behaviour is dependent on the surface characteristics of the nanoparticles.