Background: The use of euglycemic diabetic ketoacidosis (EDKA) related to sodium-glucose cotransporter 2 inhibitors (SGLT2i) use in people with diabetes has been increasingly reported. The causes are multifactorial, and dietary changes in SGLT2i users were observed to trigger EDKA. A ketogenic diet or very low-carbohydrate diet (VLCD) enhances body ketosis by breaking down fats into energy sources, causing EDKA. This study aimed to understand the patient specific risk factors and clinical characteristics of this cohort. Methods: Several databases were carefully analyzed to understand the patients’ symptoms, clinical profile, laboratory results, and safety of dietary changes in SGLT2i’s. Thirteen case reports identifying 14 patients on a ketogenic diet and SGLT2i’s diagnosed with EDKA were reviewed. Results: Of the 14 patients, 12 (85%) presented with type-2 diabetes mellitus (DM) and 2 (15%) presented with type-1 DM. The duration of treatment with SGLT2i before the onset of EDKA varies from 1 to 365 days. The duration of consuming a ketogenic diet or VLCD before EDKA onset varies from 1 to 90 days, with over 90% of patients hospitalized <4 weeks after starting the diet. At presentation, average blood glucose was 167.50±41.80 mg/dL, pH 7.10±0.10, HCO3 8.1±3.0 mmol/L, potassium 4.2±1.1 mEq/L, anion-gap 23.6±3.5 mmol/L, and the average hemoglobin A1c was 10%±2.4%. The length of hospital stay ranged from 1 to 15 days. None of the patients were reinitiated on SGLT2i’s, and 50% (2/4) of the patients reported were on the ketogenic diet or VLCD upon patient questioning. Conclusion Despite the popularity of the ketogenic diet and VLCD for weight loss, their use in diabetics taking SGLT2i’s is associated with EDKA. Physicians should educate patients with diabetes taking SGLT2i’s about the risk of EDKA. In addition, patients should be encouraged to include their physicians in any decision related to significant changes in diet or exercise routines. Further research is needed to address if SGLT2i’s should be permanently discontinued in patients with diabetes on SGLT2i and whether the ketogenic diet developed EDKA.

BACKGROUND: Tissue engineering centers on creating a niche similar to the natural one, with a purpose of developing an organ construct. A natural scaffold can replace none while creating a scaffold unique to each tissue in composition, architecture and cues that regulate the character of cells. METHODS: Whole pancreas from mouse was decellularized using detergent and enzymes, followed by recellularizing with MSC from human placenta. This construct was transplanted in streptozotocin induced diabetic mice. Histopathology of both decellularized and recellularized transplanted pancreas and qPCR analysis were performed to assess its recovery. RESULTS: Decellularization removes the cells leaving behind extracellular matrix rich natural scaffold. After reseeding with mesenchymal stem cells, these cells differentiate into pancreas specific cells. Upon transplantation in streptozotocin induced diabetic mice, this organ was capable of restoring its histomorphology and functioning. Restoration of endocrine (islets), the exocrine region (acinar) and vascular network was seen in transplanted pancreas. The process of functional recovery of endocrine system took about 20 days when the mice start showing blood glucose reduction, though none achieved gluconormalization. CONCLUSION Natural decellularized scaffolds of soft organs can be refunctionalized using recipient’s mesenchymal stem cells to restore structure and function; and counter immune problems arising during transplantation.

Amorphous solid dispersions (ASDs) are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs. Various approaches have been employed to produce ASDs and novel techniques are emerging. This review provides an updated overview of manufacturing techniques for preparing ASDs. As physical stability is a critical quality attribute for ASD, the impact of formulation, equipment, and process variables, together with the downstream processing on physical stability of ASDs have been discussed. Selection strategies are proposed to identify suitable manufacturing methods, which may aid in the development of ASDs with satisfactory physical stability.

BACKGROUND: Tissue engineering centers on creating a niche similar to the natural one, with a purpose of developing an organ construct. A natural scaffold can replace none while creating a scaffold unique to each tissue in composition, architecture and cues that regulate the character of cells. METHODS: Whole pancreas from mouse was decellularized using detergent and enzymes, followed by recellularizing with MSC from human placenta. This construct was transplanted in streptozotocin induced diabetic mice. Histopathology of both decellularized and recellularized transplanted pancreas and qPCR analysis were performed to assess its recovery. RESULTS: Decellularization removes the cells leaving behind extracellular matrix rich natural scaffold. After reseeding with mesenchymal stem cells, these cells differentiate into pancreas specific cells. Upon transplantation in streptozotocin induced diabetic mice, this organ was capable of restoring its histomorphology and functioning. Restoration of endocrine (islets), the exocrine region (acinar) and vascular network was seen in transplanted pancreas. The process of functional recovery of endocrine system took about 20 days when the mice start showing blood glucose reduction, though none achieved gluconormalization. CONCLUSION Natural decellularized scaffolds of soft organs can be refunctionalized using recipient’s mesenchymal stem cells to restore structure and function; and counter immune problems arising during transplantation.

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is associated with exaggerated cerebral response including emotional processing following visceral stimulation; though data on this issue is available in female IBS patients, it is scanty among males. Hence, we aimed to study brain response of male IBS patients following rectal balloon distension as compared to healthy controls using functional magnetic resonance imaging (fMRI). Data between diarrhea and constipation predominant IBS (IBS-D and IBS-C) were also compared. METHODS: Rectal balloon distension threshold was assessed in 20 male IBS patients (10 IBS-C and 10 IBS-D) and 10 age-matched male healthy controls. Subsequently, fMRI on all the participants was performed at their respective rectal pain threshold. The fMRI data were analysed using the Statistical Parametric Mapping software. RESULTS: IBS patients showed greater cerebral activations in insula, middle temporal gyrus, and cerebellum in the left hemisphere compared to healthy controls. Neural activation was found in bilateral precuneus/superior parietal lobules in controls but not in patients with IBS. The brain activation differed among IBS-C and IBS-D patients; while the right mid-cingulate cortex was activated in IBS-C, the left inferior orbito-frontal cortex, left calcarine, and bilateral fusiform gyri were activated among patients with IBS-D following rectal balloon distension. CONCLUSIONS: Brain response to rectal balloon distension differed among male patients with IBS and controls and among patients with IBS-C and IBS-D. Differential activation among patients with IBS-C and IBS-D was seen in the brain regions controlling affective motivation, homeostatic emotions, and autonomic responses to pain.
Brain* ; Cerebellum ; Constipation ; Diarrhea ; Female ; Humans ; Irritable Bowel Syndrome* ; Magnetic Resonance Imaging* ; Male* ; Motivation ; Pain Threshold ; Parietal Lobe ; Temporal Lobe

No abstract available.
Pedicle Screws* ; Spondylolisthesis*

OBJECTIVETo formulate diclofenac sodium as fast dissolving tablets (FDTs) using fenugreek gum as a natural superdisintegrant which also possess anti-inflammatory activity.

METHODSAn attempt was made to extract the fenugreek gum and evaluated it for various physicochemical characterizations. The swelling index and viscosity of fenugreek gum was 221% and 293.4 mpa.s respectively. FDTs of diclofenac sodium was formulated by direct compression technique using different concentrations (1%-6%, w/w) of fenugreek gum as a natural superdisintegrant and compared with renowned synthetic superdisintegrants like sodium starch glycolate and croscarmellose sodium. The anti-inflammatory activity of a formulation was evaluated with carrageenan induced experimental rats.

RESULTSThe formulated tablets were evaluated for various physical tests like weight variation, friability, hardness and results complied with the limits. The drug release from all the formulations ascertained first order kinetics. Among all the formulations F3 containing fenugreek gum with the concentration of 6% produced least disintegrating time 21 seconds resulting in higher drug release rate 93.74% at the end of 25 min. Hence, it was considered as optimized formulation. The present study revealed that the fenugreek gum as a natural superdisintegrant showed better disintegrating property than the most widely used synthetic superdisintegrants like sodium starch glycolate and croscarmellose sodium in the formulations of FDTs.

CONCLUSIONSThe results suggested that the fenugreek gum act as a good super disintegrating agent and it showed promising additive anti-inflammatory activity with diclofenac sodium.

This study assesses inter-examiner reproducibility in recording various malocclusion parameters and Index of Orthodontic Treatment Need (IOTN) grade during patient examination by utilising the kappa statistic. Five previously calibrated orthodontists clinically examined 233 non-orthodontically treated schoolchildren aged 14-17 years for recording various malocclusion parameters. The examination was repeated twice, thirty days apart and precluded the use of study-models or radiographs. Although good inter-examiner reproducibility was observed in recording incisor class, IOTN dental health grade, type of posterior crossbite, and excellent for parameters with absolute criteria like erupted supernumeraries, etc, substantial examiner variation resulted in only fair reproducibility for recording IOTN esthetic category, canine class, overbite category, traumatic overbite and upper centre-line shift of two millimetres or more from the facial midline. Reproducibility for detecting occlusal displacement in the presence of crossbite was poor, and kappa statistic was incalculable for recording openbite and number of upper incisors rotated 30° or more. Kappa was also incalculable for recording IOTN dental health subcategory due to the creation of asymmetric tables caused by rarely chosen subcategory options. Despite prior agreement between previously calibrated examiners on evaluation criteria, detection of certain malocclusion parameters during an epidemiological examination can prove to be challenging. Epidemiological studies that report on prevalence of malocclusion in the population should always report on the kappa reproducibility, especially if the study is carried out by multiple examiners.
Malocclusion ; Orthodontics ; Epidemiologic Studies

Objective: To formulate diclofenac sodium as fast dissolving tablets (FDTs) using fenugreek gum as a natural superdisintegrant which also possess anti-inflammatory activity.Methods:physicochemical characterizations. The swelling index and viscosity of fenugreek gum was 221% and 293.4 mpa.s respectively. FDTs of diclofenac sodium was formulated by direct compression technique using different concentrations (1%-6%, w/w) of fenugreek gum as a natural superdisintegrant and compared with renowned synthetic superdisintegrants like sodium starch glycolate and croscarmellose sodium. The anti-inflammatory activity of a formulation was evaluated with carrageenan induced experimental rats.Results:An attempt was made to extract the fenugreek gum and evaluated it for various friability, hardness and results complied with the limits. The drug release from all the formulations ascertained first order kinetics. Among all the formulations F3 containing fenugreek gum with the concentration of 6% produced least disintegrating time 21 seconds resulting in higher drug release rate 93.74% at the end of 25 min. Hence, it was considered as optimized formulation. The present study revealed that the fenugreek gum as a natural superdisintegrant showed better disintegrating property than the most widely used synthetic superdisintegrants like sodium starch glycolate and croscarmellose sodium in the formulations of FDTs. The formulated tablets were evaluated for various physical tests like weight variation, Conclusions: The results suggested that the fenugreek gum act as a good super disintegrating agent and it showed promising additive anti-inflammatory activity with diclofenac sodium.

Animals ; Bone and Bones ; drug effects ; Copper ; pharmacology ; therapeutic use ; Fluoride Poisoning ; prevention & control ; Fluorides ; blood ; toxicity ; urine ; Lipid Metabolism ; drug effects ; Molybdenum ; toxicity ; Rabbits ; Trace Elements ; pharmacology ; therapeutic use