A cellular and molecular spatial atlas of dystrophic muscle.

Asynchronous skeletal muscle degeneration/regeneration is a hallmark feature of Duchenne muscular dystrophy (DMD); however, traditional -omics technologies that lack spatial context make it difficult to study the biological mechanisms of how asynchronous regeneration contributes to disease progression. Here, using the severely dystrophic D2-mdx mouse model, we generated a high-resolution cellular and molecular spatial atlas of dystrophic muscle by integrating spatial transcriptomics and single-cell RNAseq datasets. Unbiased clustering revealed nonuniform distribution of unique cell populations throughout D2-mdx muscle that were associated with multiple regenerative timepoints, demonstrating that this model faithfully recapitulates the asynchronous regeneration observed in human DMD muscle. By probing spatiotemporal gene expression signatures, we found that propagation of inflammatory and fibrotic signals from locally damaged areas contributes to widespread pathology and that querying expression signatures within discrete microenvironments can identify targetable pathways for DMD therapy. Overall, this spatial atlas of dystrophic muscle provides a valuable resource for studying DMD disease biology and therapeutic target discovery.

Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

BACKGROUND AND AIMS: The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival. METHODS: Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival. RESULTS: One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival. CONCLUSIONS: In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.

Clinical efficacy of gastric per-oral endoscopic myotomy (G-POEM) in the treatment of refractory gastroparesis and predictors of outcomes: a systematic review and meta-analysis using surgical pyloroplasty as a comparator group.

BACKGROUND AND AIMS: Gastric peroral endoscopic myotomy (G-POEM) is a novel minimally invasive technique in endosurgery. Data is limited as to its efficacy, safety, and predictive factors. We conducted this meta-analysis to evaluate the clinical outcomes of G-POEM and used the outcomes of surgical pyloroplasty as a comparator group in the treatment of refractory gastroparesis. METHODS: We searched multiple databases from inception through March 2019 to identify studies that reported on G-POEM and pyloroplasty in gastroparesis. Our primary outcome was to analyze and compare the pooled rates of clinical success, in terms of Gastroparesis Cardinal Symptom Index (GCSI) score and 4-h gastric emptying study (GES) results, with G-POEM and pyloroplasty. RESULTS: Three hundred and thirty-two and 375 patients underwent G-POEM (11 studies) and surgical pyloroplasty (seven studies), respectively. The pooled rate of clinical success, based on the GCSI score, with G-POEM was 75.8% (95% CI 68.1-82.1, I2 = 50) and with surgical pyloroplasty was 77.3% (95% CI 66.4-85.4, I2 = 0), with no significance, p = 0.81. The pooled rate of clinical success, based on the 4-hour GES results, with G-POEM was 85.1% (95% CI 68.9-93.7, I2 = 74) and with surgical pyloroplasty was 84% (95% CI 64.4-93.8, I2 = 81), with no significance, p = 0.91. The overall adverse events were comparable. Based on meta-regression analysis, idiopathic gastroparesis, prior treatment with botulinum toxin and gastric stimulator seemed to predict clinical success with G-POEM. CONCLUSION: G-POEM demonstrates clinical success in treating refractory gastroparesis. Idiopathic gastroparesis, prior treatment with botulinum injections and gastric stimulator appear to have positive predictive effects on the 4-h GES results after G-POEM. Outcomes seem comparable to surgical pyloroplasty.

Synthesis and an angiolytic role of novel piperazine-benzothiazole analogues on neovascularization, a chief tumoral parameter in neoplastic development.

A novel series of benzoic acid N'-[2-(4-benzothiazol-2-yl-piperazin-1-yl)-acetyl]-hydrazides 6a-j were synthesized and characterized by IR, (1)H, (13)C NMR, elemental and mass spectral analyses. The in-vitro cytotoxicity and cell viability assay of the synthesized compounds 6a-j were evaluated against Dalton's lymphoma ascites (DLA) cells. Our results showed that compound 6c with a bromo group on phenyl ring has showed promising antiproliferative efficacy. Further investigation of compound 6c on in-vivo treatment model depicts the increased tumor suppression through inhibition of angiogenesis.

Atypical Presentation of Right Ventricular Outflow Tract Ventricular Tachycardia.

BACKGROUND: Ventricular tachycardia (VT) in the pediatric population is rare, has a wide differential diagnosis, and can present in numerous ways. In the absence of underlying heart disease, VT is considered idiopathic and is associated with an excellent prognosis. Right ventricular outflow tract ventricular tachycardia (RVOT-VT) represents the most common form of idiopathic VT. The differential diagnosis, mechanism, presentation, management, and prognosis of RVOT-VT in the pediatric population will be discussed. CASE REPORT: We report a case of RVOT-VT that was incidentally discovered in an 11-year-old girl during an emergency department workup for severe headache. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is essential for emergency physicians to have an approach to pediatric VT and appreciate the wide range of potential presentations. Differentiating idiopathic VT, such as RVOT-VT, from more malignant forms of VT can be challenging and requires expert consultation for further diagnostic workup and management.

Synthesis, xanthine oxidase inhibition, and antioxidant screening of benzophenone tagged thiazolidinone analogs.

A series of novel 2-(diaryl methanone)-N-(4-oxo-2-phenyl-thiazolidin-3-yl)-acetamides were synthesized by various Schiff bases of (4-benzoyl-phenoxy)-aceto hydrazide with thioglycolic acid. The structures of the newly synthesized compounds were confirmed by IR, (1) H NMR, mass spectra, and C, H, N analysis. Further, all the synthesized compounds 9a-n were evaluated for xanthine oxidase (XO) inhibition and antioxidant properties. Among all the tested compounds, 9f, 9m, and 9n demonstrated potent XO inhibition of 52, 76, and 26%, respectively, compared to the standard drug allopurinol, which is evident from in vitro and in silico analysis. On the other hand, compounds 9c, 9d, and 9k exhibit potent antioxidant properties.

Maternal Experiences during Pregnancy, Delivery, and Breastfeeding Practices: A Community-based Analytical Cross-sectional Study.

Background: Evidence on variation in the information provided to mothers during antenatal and postnatal periods, its influence on breastfeeding awareness, and practice in urban and rural settings of India is scarce. The aim of the study was to assess the variation in mothers experience during pregnancy, delivery, and maternity period across settings and its influence on breastfeeding practices in the first six months of infants' life. Methods: A community-based analytical cross-sectional study was carried out in urban and rural settings of Coimbatore, Tamil Nadu, among 800 mothers who had delivered between one year and six months before the date of the survey using simple random sampling. Results: The proportion of mothers with less than four antenatal visits were significantly higher in urban areas (urban vs rural, 11.4% vs 6.2%). The mean scores for positive experiences during pregnancy (MD -0.99, 95% CI -1.31 to -0.69), experiences during birth and maternity period (MD -0.59, 95% CI -0.83 to -0.35) were significantly lower in the urban areas compared to rural areas. The prevalence of exclusive breastfeeding was 75.8% and 85.0% in urban and rural areas, respectively. Mothers not satisfied with experiences during delivery and maternity period (OR 1.69, 95% CI 1.18 to 2.42) and from urban areas (OR 1.81, 95% CI 1.27 to 2.59) were at significantly increased risk of nonexclusive breastfeeding. Conclusion: The present study showed that mothers from urban areas were not provided with appropriate, adequate, and timely information by the healthcare providers. It is the need of the hour to train and motivate healthcare providers regarding maternal awareness of antenatal, intranatal, and postnatal care practices including breastfeeding and infant care.

PTH like substance secreting mesenchymal tumor causing oncogenic osteomalacia; unravelling the difficulties in localization - A report of 2 cases.

Background: Oncogenic osteomalacia is a rare paraneoplastic association of Phosphaturic mesenchymal tumor (PMT) secreting excessive levels of a PTH like substance. They usually remain undiagnosed and patients suffer for years. The rarity of this tumor and its non-specific clinical presentations poses great challenge to the treating surgeons. Its management is poorly described in literature. We report two of such rare cases without much diagnostic delay. Case report: We had 2 cases; A 53-year-old south east Asian male with 6 months of debilitating pain over multiple sites, and another 44-year-old male patient with complaints of low back ache, and pain over both lower and upper limbs for 1.5 years. Both had low serum phosphorus and elevated FGF-23 values, but all other parameters were normal. A PMT was suspected and confirmed on a Ga68- DOTATOC scan in both cases, and on complete excision, their symptoms and the altered blood parameters got normalized. Histology was consistent with PMT. Conclusion: Accurate and timely diagnosis of a PMT with non-specific features are extremely challenging, but not without solutions. Even though a tumor of rarity, with the appropriate imaging modalities like Ga68- DOTATOC scan, and estimation of FGF-23 and serum phosphorus levels, they can be diagnosed. Once identified, complete removal is often curative within a few months.

Incorporating Patient Values in Large Language Model Recommendations for Surrogate and Proxy Decisions.

BACKGROUND: Surrogates, proxies, and clinicians making shared treatment decisions for patients who have lost decision-making capacity often fail to honor patients' wishes, due to stress, time pressures, misunderstanding patient values, and projecting personal biases. Advance directives intend to align care with patient values but are limited by low completion rates and application to only a subset of medical decisions. Here, we investigate the potential of large language models (LLMs) to incorporate patient values in supporting critical care clinical decision-making for incapacitated patients in a proof-of-concept study. METHODS: We simulated text-based scenarios for 50 decisionally incapacitated patients for whom a medical condition required imminent clinical decisions regarding specific interventions. For each patient, we also simulated five unique value profiles captured using alternative formats: numeric ranking questionnaires, text-based questionnaires, and free-text narratives. We used pre-trained generative LLMs for two tasks: 1) text extraction of the treatments under consideration and 2) prompt-based question-answering to generate a recommendation in response to the scenario information, extracted treatment, and patient value profiles. Model outputs were compared with adjudications by three domain experts who independently evaluated each scenario and decision. RESULTS AND CONCLUSIONS: Automated extractions of the treatment in question were accurate for 88% (n = 44/50) of scenarios. LLM treatment recommendations received an average Likert score by the adjudicators of 3.92 of 5.00 (five being best) across all patients for being medically plausible and reasonable treatment recommendations, and 3.58 of 5.00 for reflecting the documented values of the patient. Scores were highest when patient values were captured as short, unstructured, and free-text narratives based on simulated patient profiles. This proof-of-concept study demonstrates the potential for LLMs to function as support tools for surrogates, proxies, and clinicians aiming to honor the wishes and values of decisionally incapacitated patients.

Effect of trichloromethane on the bond strengths between acrylic teeth and different heat-cured denture bases: a comparative study.

AIM: This study is to evaluate the role of 1:1 v/v 30% trichloromethane and monomer solvent in enhancing the durability of bonding between cross-linked acrylic teeth and different heatcured denture bases with or without mechanical preparations made on ridge lap portion of the artificial teeth. MATERIALS AND METHODS: Two high impact denture base resin materials (Trevalon HI, DeTrey, UK, and DPI Tuff, Mumbai) and one nonhigh impact denture base resin material (DPI Quick Set, Mumbai) were selected to form three groups. Each group contains 30 specimens prepared by five different methods. A mixture of 30% trichloromethane and monomer, mixed in the ratio of 1:1 and applied for 1 minute on the ridge lap area of experimental specimens of methods--B, C, D and E (Specimens of method--A being control group, where no alterations were made at the ridge lap portion of acrylic teeth) before curing. Hounsfield universal testing machine is employed to evaluate the comparative bond strengths. RESULTS: No significant difference was seen in bond strengths between specimens of experimental methods in all groups. When each group was assessed separately method B specimens in group 1 (739.2 N), group 2 (758 N) and method D specimens in group 3 (729 N) showed highest mean bond strengths. Control group specimens showed the least bond strength (400-460 N) in all groups with more adhesive failures. CONCLUSION: Ridge lap portion of the specimens treated with chemical solvent as in method B showed increased bond strength in groups 1 and 2. Hence, this is a preferred method. CLINICAL SIGNIFICANCE: Evaluation of effect of different chemical and mechanical preparations at the ridge lap areas of acrylic teeth before acrylization helps the clinician and technician to overcome the problem of debonding of teeth from denture bases and in turn provides better quality prosthesis to the patient.

A Novel Intelligent Hybrid Optimized Analytics and Streaming Engine for Medical Big Data.

Medical data processing is exponentially increasing day by day due to the frequent demand for many applications. Healthcare data is one such field, which is dynamically growing day by day. In today's scenario, an enormous amount of sensing devices and data collection units have been employed to generate and collect medical data all over the world. These healthcare devices will result in big real-time data streams. Hence, healthcare-based big data analytics and monitoring have gained hawk-eye importance but needs improvisation. Recently, machine and deep learning algorithms have gained importance to analyze huge amounts of medical data, extract the information, and even predict the future insights of diseases and also cope with the huge volume of data. But applying the learning models to handle big/medical data streams remains to be a challenge among the researchers. This paper proposes the novel deep learning electronic record search engine algorithm (ERSEA) along with firefly optimized long short-term memory (LSTM) model for better data analytics and monitoring. The experimentations have been carried out using Apache Spark using the different medical respiratory data. Finally, the proposed framework results are contrasted with existing models. It shows the accuracy, sensitivity, and specificity like 94%, 93.5%, and 94% for less than 5 GB dataset, and also, more than 5 GB it provides 94%, 92%, and 93% to prove the extraordinary performance of the proposed framework.

Acid-Mediated Kidney Injury Across the Spectrum of Metabolic Acidosis.

Metabolic acidosis affects about 15% of patients with chronic kidney disease. As kidney function declines, the kidneys progressively fail to eliminate acid, primarily reflected by a decrease in ammonium and titratable acid excretion. Several studies have shown that the net acid load remains unchanged in patients with reduced kidney function; the ensuing acid accumulation can precede overt metabolic acidosis, and thus, indicators of urinary acid or potential base excretion, such as ammonium and citrate, may serve as early signals of impending metabolic acidosis. Acid retention, with or without overt metabolic acidosis, initiates compensatory responses that can promote tubulointerstitial fibrosis via intrarenal complement activation and upregulation of endothelin-1, angiotensin II, and aldosterone pathways. The net effect is a cycle between acid accumulation and kidney injury. Results from small- to medium-sized interventional trials suggest that interrupting this cycle through base administration can prevent further kidney injury. While these findings inform current clinical practice guidelines, large-scale clinical trials are still necessary to prove that base therapy can limit chronic kidney disease progression or associated adverse events.

An Unusual Case of Candida kefyr Fungemia in an Immunocompromised Patient.

An immunocompromised patient with a known history of cerebrovascular accident (CVA) with right-sided hemiparesis of long duration, type 2 diabetes mellitus, and hypertension presented with signs of rhabdomyolysis and later acute kidney injury (AKI). He subsequently developed Guillain Barre syndrome. Initially, hemodialysis was followed by plasmapheresis. After hemodialysis, the patient presented with multiple episodes of vomiting and weakness of all limbs. A culture showed growth of Enterococcus faecalis, and on Day 6, a bloodstream infection with Candida kefyr and a urinary tract infection with Enterococcus faecalis were diagnosed. We report a rare case of bloodstream infection due to C. kefyr.

A standardized black pepper seed extract containing ß-caryophyllene improves cognitive function in scopolamine-induced amnesia model mice via regulation of brain-derived neurotrophic factor and MAPK proteins.

ß-caryophyllene (BCP), a natural sesquiterpene present in plants, is a selective agonist of cannabinoid receptor type-2 (CB2) of the endocannabinoid system. In this study, we have prepared an extract from Piper nigrum (black pepper) seeds using supercritical fluid extraction, standardized to contain 30% BCP (ViphyllinTM ). The beneficial effects of prophylactic treatment with Viphyllin on cognitive functions were demonstrated in Scopolamine-induced dementia model mice. Male Swiss albino mice (25-30 g) were administered with Viphyllin (50 mg and 100 mg/kg body weight p.o.) or donepezil (1.60 mg/kg) for 14 days. Subsequently, cognitive deficits were induced by treating the animals intraperitoneally with Scopolamine (0.75 mg/kg). The cognitive behavior of mice was evaluated using a novel object recognition test (NORT) and Morris water maze (MWM) test. The brain homogenates were studied for biochemical parameters including cholinesterase activities and antioxidant status. Western blot analysis was performed to investigate the mechanism of action. Viphyllin dose dependently improved the recognition and spatial memory and cholinergic functions in Scop-treated mice. The extract was found protective against Scop-induced oxidative damage and histopathologic changes in the brain. At 100 mg/kg Viphyllin markedly reduced the proBDNF/mBDNF ratio (p < .05) and augmented the TrkB expression (p < .01). Viphyllin (100 mg/kg) was found to be neuroprotective by reducing the Scop-induced upregulation of p-JNK and p-p38 MAPK proteins, Bax/Bcl-2 ratio, and caspase activation in the brain. Viphyllin also exerted anti-inflammatory effects by downregulating Cox-2, TNF-α, and NOS-2 in Scop-induced mice (p < .05). To summarize, our data encourage Viphyllin as a functional ingredient/dietary supplement for brain health and cognition. PRACTICAL APPLICATIONS: Black pepper is a culinary spice having several medicinal attributes. Essential oils in the seeds of the plant give aroma and flavor to it. Here we have prepared an extract from the seeds of black pepper using supercritical fluid extraction, characterized for the presence of ß-caryophyllene (not <30%). This research work further validates the neuroprotective mechanism of the extract in Scopolamine-induced cognitive impairment model mice. The findings from this study strongly suggest the beneficial neuroactive properties of black pepper seed extract having the presence of BCP, a CB2 receptor agonist. It can thus be used potentially as a functional food ingredient for cognition and brain function.

PGC-1α isoforms coordinate to balance hepatic metabolism and apoptosis in inflammatory environments.

OBJECTIVE: The liver is regularly exposed to changing metabolic and inflammatory environments. It must sense and adapt to metabolic need while balancing resources required to protect itself from insult. Peroxisome proliferator activated receptor gamma coactivator-1 alpha (PGC-1α) is a transcriptional coactivator expressed as multiple, alternatively spliced variants transcribed from different promoters that coordinate metabolic adaptation and protect against inflammation. It is not known how PGC-1α integrates extracellular signals to balance metabolic and anti-inflammatory outcomes. METHODS: Primary mouse hepatocytes were used to evaluate the role(s) of different PGC-1α proteins in regulating hepatic metabolism and inflammatory signaling downstream of tumor necrosis factor alpha (TNFα). Gene expression and signaling analysis were combined with biochemical measurement of apoptosis using gain- and loss-of-function in vitro and in vivo. RESULTS: Hepatocytes expressed multiple isoforms of PGC-1α, including PGC-1α4, which microarray analysis showed had common and isoform-specific functions linked to metabolism and inflammation compared with canonical PGC-1α1. Whereas PGC-1α1 primarily impacted gene programs of nutrient metabolism and mitochondrial biology, TNFα signaling showed several pathways related to innate immunity and cell death downstream of PGC-1α4. Gain- and loss-of-function models illustrated that PGC-1α4 uniquely enhanced expression of anti-apoptotic gene programs and attenuated hepatocyte apoptosis in response to TNFα or lipopolysaccharide (LPS). This was in contrast to PGC-1α1, which decreased the expression of a wide inflammatory gene network but did not prevent hepatocyte death in response to cytokines. CONCLUSIONS: PGC-1α variants have distinct, yet complementary roles in hepatic responses to metabolism and inflammation, and we identify PGC-1α4 as an important mitigator of apoptosis.

Interaction of sanguinarine alkaloid, isolated from argemone oil, with hepatic cytochrome p450 in rats.

ABSTRACT Prior studies have shown that argemone oil (AO), responsible for 'Epidemic dropsy', causes inhibition of catalytic activities of Cytochrome P450 (P450). In this study interaction of sanguinarine (SAN) alkaloid, isolated from AO, with rat hepatic P450 was investigated. Hepatic microsomes prepared from 3-methylcholantherene (3MC) treated rats when incubated with SAN (1-3 muM) resulted in a spectral peak at 385 nm and a trough at 415 nm, indicative of Type I binding. Incubation of SAN (50-200 muM) with hepatic microsomes prepared from phenobarbitone (PB) treated rats also showed a Type I spectra with a peak at 395 nm and a trough at 420 nm. Relative binding efficiency (DeltaA(max)/K(s)(app) factor) of SAN with P450 was found to be 1540 and 1030 absorbance units/nmol CYP/M for 3MC and PB induced microsomes, respectively. In a P450 spectral inhibition study SAN showed higher affinity towards 3MC eliciting inhibition at much lesser concentrations (0.25-5 muM) as compared to PB (100-300 muM). The IC50s of SAN with different catalytic markers of P450 isoforms, i.e. ethoxyresorufin-O-deethylase (EROD) for CYP1A1, was 2.8 muM and for methoxyresorufin-O-deethylase (MROD) for CYP1A2 was 2.2 muM in 3MC induced microsomes, while benzoyloxyresorufin-O-deethylase (BROD) for CYP 2B1/1A1 showed an IC50 of 50 muM but pentoxyresorufin-O-deethylase (PROD) for CYP2B1 showed no inhibition even at higher concentrations of SAN (> 60 muM) in PB-induced microsomes. These results indicate that higher affinity of SAN binding towards the CYP1A family may have a role in SAN toxicity.

Method Development and Validation for the Determination of Caffeine: An Alkaloid from Coffea arabica by High-performance Liquid Chromatography Method.

OBJECTIVE: The present study was investigated to develop and validate a reversed phase high performance liquid chromatography method for the determination of caffeine from bean material of Coffee arabica. MATERIALS AND METHODS: The separation was achieved on a reversed-phase C18 column using a mobile phase composed of water: methanol (50:50) at a flow rate of 1.0 mlmin-1. The detection was carried out on a UV detector at 272 nm. The developed method was validated according to the requirements for International Conference on Harmonisation (ICH) guidelines, which includes specificity, linearity, precision, accuracy, limit of detection and limit of quantitation. RESULTS: The developed method validates good linearity with excellent correlation coefficient (R2 > 0.999). In repeatability and intermediate precision, the percentage relative standard deviation (% RSD) of peak area was less than 1% shows high precision of the method. The recovery rate for caffeine was within 98.78% - 101.28% indicates high accuracy of the method. The low limit of detection and limit of quantitation of caffeine enable the detection and quantitation of caffeine from C. arabica at low concentrations. CONCLUSION: The developed HPLC method is a simple, rapid, precisely, accurately and widely accepted and it is recommended for efficient assays in routine work. SUMMARY: A simple, accurate, and sensitive high-performance liquid chromatography (HPLC) method for caffeine from Coffea arabica has been developed and validated. The developed HPLC method was validated for linearity, specificity, precision, recovery, limits of detection, and limits of quantification by the International Conference on Harmonization guidelines. The results revealed that the proposed method is highly reliable. This method could be successfully applied for routine quality work analysis.Abbreviation Used:C. arabica: Coffee arabica, ICH: International Conference on Harmonisation, % RSD: Percentage Relative Standard Deviation, R2: Correlation Coefficient, ppm: Parts per million, LOD: Limits of detection, LOQ: Limits of quantification, SD: Standard deviation, S: Slope, RP-HPLC: Reverse phase high performance liquid chromatography, v/v: Volume per volume.

Linking Metabolic Disease With the PGC-1α Gly482Ser Polymorphism.

Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) is a highly conserved transcriptional coactivator enriched in metabolically active tissues including liver, adipose, pancreas, and muscle. It plays a role in regulating whole body energy metabolism and its deregulation has been implicated in type 2 diabetes (T2D). A single nucleotide variant of the PPARGC1A gene (rs8192678) is associated with T2D susceptibility, relative risk of obesity and insulin resistance, and lower indices of ß cell function. This common polymorphism is within a highly conserved region of the bioactive protein and leads to a single amino acid substitution (glycine 482 to serine). Its prevalence and effects on metabolic parameters appear to vary depending on factors including ethnicity and sex, suggesting important interactions between genetics and cultural/environmental factors and associated disease risk. Interestingly, carriers of the serine allele respond better to some T2D interventions, illustrating the importance of understanding functional impacts of genetic variance on PGC-1α when targeting this pathway for personalized medicine. This review summarizes a growing body of literature surrounding possible links between the PGC-1α Gly482Ser single nucleotide polymorphism and diabetes, with focus on key clinical findings, affected metabolic systems, potential molecular mechanisms, and the influence of geographical or ethnic background on associated risk.

Rapid Development and Validation of Improved Reversed-Phase High-performance Liquid Chromatography Method for the Quantification of Mangiferin, a Polyphenol Xanthone Glycoside in Mangifera indica.

Mangiferin, a polyphenolic xanthone glycoside from Mangifera indica, is used as traditional medicine for the treatment of numerous diseases. The present study was aimed to develop and validate a reversed-phase high-performance liquid chromatography (RP-HPLC) method for the quantification of mangiferin from the bark extract of M. indica. RP-HPLC analysis was performed by isocratic elution with a low-pressure gradient using 0.1% formic acid: acetonitrile (87:13) as a mobile phase with a flow rate of 1.5 ml/min. The separation was done at 26°C using a Kinetex XB-C18 column as stationary phase and the detection wavelength at 256 nm. The proposed method was validated for linearity, precision, accuracy, limit of detection, limit of quantification, and robustness by the International Conference on Harmonisation guidelines. In linearity, the excellent correlation coefficient more than 0.999 indicated good fitting of the curve and also good linearity. The intra- and inter-day precision showed < 1% of relative standard deviation of peak area indicated high reliability and reproducibility of the method. The recovery values at three different levels (50%, 100%, and 150%) of spiked samples were found to be 100.47, 100.89, and 100.99, respectively, and low standard deviation value < 1% shows high accuracy of the method. In robustness, the results remain unaffected by small variation in the analytical parameters, which shows the robustness of the method. Liquid chromatography-mass spectrometry analysis confirmed the presence of mangiferin with M/Z value of 421. The assay developed by HPLC method is a simple, rapid, and reliable for the determination of mangiferin from M. indica. SUMMARY: The present study was intended to develop and validate an RP-HPLC method for the quantification of mangiferin from the bark extract of M. indica. The developed method was validated for linearity, precision, accuracy, limit of detection, limit of quantification and robustness by International Conference on Harmonization guidelines. This study proved that the developed assay by HPLC method is a simple, rapid and reliable for the quantification of the mangiferin from M. indica. Abbreviations Used:M. indica: Mangifera indica, RP-HPLC: Reversed-phase high-performance liquid chromatography, M/Z: Mass to charge ratio, ICH: International conference on harmonization, % RSD: Percentage of relative standard deviation, ppm: Parts per million, LOD: Limit of detection, LOQ: Limit of quantification.

A patient with serum creatinine of 61 mg/dl.

Spurious elevation of serum creatinine by Jaffe assay is known to occur due to a variety of substances. This results in subjecting the patient to invasive and complicated procedures such as dialysis. We report a rare case of false elevation of this renal parameter following exposure to an organic solvent.