"Millet Models" for harnessing nuclear factor-Y transcription factors to engineer stress tolerance in plants: current knowledge and emerging paradigms.

MAIN CONCLUSION: The main purpose of this review is to shed light on the role of millet models in imparting climate resilience and nutritional security and to give a concrete perspective on how NF-Y transcription factors can be harnessed for making cereals more stress tolerant. Agriculture faces significant challenges from climate change, bargaining, population, elevated food prices, and compromises with nutritional value. These factors have globally compelled scientists, breeders, and nutritionists to think of some options that can combat the food security crisis and malnutrition. To address these challenges, mainstreaming the climate-resilient and nutritionally unparalleled alternative crops like millet is a key strategy. The C4 photosynthetic pathway and adaptation to low-input marginal agricultural systems make millets a powerhouse of important gene and transcription factor families imparting tolerance to various kinds of biotic and abiotic stresses. Among these, the nuclear factor-Y (NF-Y) is one of the prominent transcription factor families that regulate diverse genes imparting stress tolerance. The primary purpose of this article is to shed light on the role of millet models in imparting climate resilience and nutritional security and to give a concrete perspective on how NF-Y transcription factors can be harnessed for making cereals more stress tolerant. Future cropping systems could be more resilient to climate change and nutritional quality if these practices were implemented.

Skin Physiology, Mucosal Functions, and Symptoms Are Modulated by Grass Pollen and Ozone Double Exposure in Allergic Patients.

INTRODUCTION: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. METHODS: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. RESULTS: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. CONCLUSION: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.

Recent updates on clinical developments of curcumin and its derivatives.

Curcumin, a natural polyphenol, derived from Curcuma longa L. is extensively studied by various researchers across the globe and has established its immense potential in the management of several disorders at clinical level. The underlying mechanism of curcumin involves regulation of various molecular targets, namely, inflammatory cytokines, transcription factor, apoptotic genes, growth factors, oxidative stress biomarkers, and protein kinases. In clinical trials, curcumin as an adjuvant has significantly boost-up the efficacy of many proven drugs in the management of arthritis, neurodegenerative disorder, oral infection, and gastrointestinal disorders. Moreover, clinical studies have suggested curcumin as an appropriate candidate for the prevention and/or management of various cancers via regulation of signaling molecules including NF-kB, cytokines, C-reactive protein, prostaglandin E2, Nrf2, HO-1, ALT, AST, kinases, and blood profiles. This article highlights plethora of clinical trials that have been conducted on curcumin and its derivatives in the management of several ailments. Besides, it provides recent updates to the investigators for conducting future research to fulfill the current gaps to expedite the curcumin utility in clinical subjects bearing different pathological states.

Mechanism insights of curcumin and its analogues in cancer: An update.

Cancer is the world's second leading cause of mortality and one of the major public health problems. Cancer incidence and mortality rates remain high despite the great advancements in existing therapeutic, diagnostic, and preventive approaches. Therefore, a quest for less toxic and more efficient anti-cancer strategies is still at the forefront of the current research. Traditionally important, curcumin commonly known as a wonder molecule has received considerable attention as an anti-cancer, anti-inflammatory, and antioxidant candidate. However, limited water solubility and low bioavailability restrict its extensive utility in different pathological states. The investigators are making consistent efforts to develop newer strategies to overcome its limitations by designing different analogues with better pharmacokinetic and pharmacodynamic properties. The present review highlights the recent updates on curcumin and its analogues with special emphasis on various mechanistic pathways involved in anti-cancer activity. In addition, the structure-activity relationship of curcumin analogues has also been precisely discussed. This article will also provide key information for the design and development of newer curcumin analogues with desired pharmacokinetic and pharmacodynamic profiles and will provide in depth understanding of molecular pathways involved in the anti-cancer activities.

Secretory phospholipase sPLA2-IIAloss impairs tumorigenic and metastatic potential in breast cancer cells.

Breast cancer stem cells (BCSCs) are slow cycling cells that escape the traditional chemo-radio-therapy, thereby contributing in resistance and recurrence. Although several markers have been identified, it is still challenging to develop strategies targeting them. In this study, we have isolated BCSCs from MCF-7 cell line using markers CD44+/CD24-/low, which showed higher percentage of mammospheres in CSC population. Moreover, in vivo tumorigenic potential of BCSCs showed as low as 10,000 cells had the ability to develop tumors when transplanted into NOD-SCID mice. We observed an increased level of EMT markers in CSC population. Overexpression of secretory phospholipase sPLA2-IIA was found in CSCs. Further, we have uncovered the upregulation of sPLA2-IIA mediated through JNK signaling in breast cancer cells whereas knockdown of sPLA2-IIA reduces JNK signaling, cell proliferation, EMT and in vivo tumorigenic potential in breast cancer cells. Our study reveals overexpression of sPLA2-IIA in two different breast cancer cells such as MCF7 (ER+,PR+) and a triple negative, MDA-MB-231 (ER-PR-HER2-). Further, the novel role of sPLA2-IIA was discerned by unraveling the molecular mechanism, which regulates the cell proliferation and metastasis in breast cancer cells.

Role of curcumin in ameliorating hypertension and associated conditions: a mechanistic insight.

Curcumin, belongs to the curcuminoid family, is a natural phenolic compound, presenting low bioavailability and pleiotropic activity. Since ancient times, curcumin has been in use as food spices and folk remedy to treat cough, cold, cuts and wounds, and skin diseases. Preclinical and clinical studies have indicated that curcumin acts a promising therapeutic agent in the management of a wide array of health issues, viz., hyperlipidemia, metabolic syndrome, anxiety, arthritis, cancer and inflammatory diseases. Owing to its enormous potential, recent research has been focused on the synthesis of curcumin and its analogues for the management of metabolic disorders. In the current scenario, hypertension is considered as a key risk factor due to its involvement in various pathogeneses. Mechanistically, curcumin and its analogues like hexahydrocurcumin, tetrahydrocurcumin, etc. have been reported to elicit anti-hypertensive effect through diverse signalling pathways, viz., pathway mediated by Nrf2-ARE, NF-kB, NO/cGMP/PDE5/MMPs, RAAS/ACE, HAT/HDAC, G0/G1/apoptosis, CYP3A4, UCP2/PARP, VEGF/STAT/AXL/tyrosine kinase and TGF-ß/Smad-mediated pathways. Thus, the present review has been aimed to highlight different molecular pathways involved in the amelioration of hypertension and associated conditions.

Ameliorating potential of curcumin and its analogue in central nervous system disorders and related conditions: A review of molecular pathways.

Curcumin, isolated from turmeric (Curcuma longa L.) is one of the broadly studied phytomolecule owing to its strong antioxidant and anti-inflammatory potential and has been considered a promising therapeutic candidate in a wide range of disorders. Considering, its low bioavailability, different curcumin analogs have been developed to afford desired pharmacokinetic profile and therapeutic outcome in varied pathological states. Several preclinical and clinical studies have indicated that curcumin ameliorates mitochondrial dysfunction, inflammation, oxidative stress apoptosis-mediated neural cell degeneration and could effectively be utilized in the treatment of different neurodegenerative diseases. Hence, in this review, we have summarized key findings of experimental and clinical studies conducted on curcumin and its analogues with special emphasis on molecular pathways, viz. NF-kB, Nrf2-ARE, glial activation, apoptosis, angiogenesis, SOCS/JAK/STAT, PI3K/Akt, ERK1/2 /MyD88 /p38 MAPK, JNK, iNOS/NO, and MMP pathways involved in imparting ameliorative effects in the therapy of neurodegenerative disorders and associated conditions.

AlRab7 from Aeluropus lagopoides ameliorates ion toxicity in transgenic tobacco by regulating hormone signaling and reactive oxygen species homeostasis.

The plants endomembrane system of the cellular compartments with its complex membrane trafficking network facilitates transport of macromolecules. The endomembrane dynamics are essential for maintaining basic and specific cellular functions including adaptation to the extracellular environment. The plant vacuole serves as a reservoir for nutrients and toxic metabolites and performs detoxification processes to maintain cellular homeostasis. The overexpression of AlRab7, a vesicle trafficking gene from Aeluropus lagopoides, improved germination and growth and reduced ionic and oxidative stress in transgenics. Moreover, the root and shoot of transgenic tobacco showed differential accumulation of phytohormone ABA and IAA with different ionic stresses. The improved growth (root and shoot length) can be co-related with higher IAA accumulation with NaCl stress. The low Na+ /K+ ratio with different NaCl stress treatments indicates better ion homeostasis in transgenics. Furthermore, the increased stomatal density and higher number of open stomata on both leaf surfaces in transgenics during NaCl stress suggest better gaseous exchange/functioning of guard cells. The maintained or increased superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase, and glutathione reductase antioxidative enzyme activities suggest that an extensive reactive oxygen species (ROS) scavenging system was triggered to detoxify cellular ROS, which remained at low levels in transgenics during the different stress treatments. Our results suggest that the AlRab7 transgenic tobacco ameliorates ionic stress by facilitating differential and selective ion transport at vacuolar membrane regulating hormone signaling, ROS homeostasis, stomatal development, and movement.

Vitamin D and cinacalcet are associated with increased survival in peritoneal dialysis but not with residual renal function preservation
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BACKGROUND: Active vitamin D and cinacalcet, a treatment for secondary hyperparathyroidism and also with potential anti-inflammatory properties, have been associated with lower risk of death among dialysis patients. Vitamin D has also been described to decrease proteinuria in CKD patients. This study aims to assess the relationship of vitamin D and cinacalcet with survival and residual renal function preservation among peritoneal dialysis patients. MATERIALS AND METHODS: In a retrospective peritoneal dialysis cohort of 581 subjects, we assessed if vitamin D and cinacalcet therapy are associated with increased risk of death and residual renal function loss using Kaplan-Meier analysis and Cox proportional hazard analysis. RESULTS: Vitamin D treatment was associated with a 56% reduction in the risk of death (HR 0.44, 95% CI 0.28 - 0.67) and cinacalcet also with a 54% lower risk of death (HR 0.46, 95% CI 0.31 - 0.69) in multivariate models adjusting for each other. Hyperphosphatemia (> 6 mg/dL) was associated with an 85% increase in mortality (HR 1.85, 95% CI 1.30 - 2.65). Neither vitamin D (HR 1.04, 95% CI 0.45 - 2.39) nor cinacalcet (HR 0.74, 95% CI 0.45 - 1.20) were associated with a lower risk of anuria. CONCLUSION: Vitamin D and cinacalcet therapy was associated with a lower risk of death but not anuria, beyond other known risk factors among peritoneal dialysis patients.
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Druggability of Intrinsically Disordered Proteins.

Although the proteins in all the current major classes considered to be druggable are folded in their native states, intrinsically disordered proteins (IDPs) are becoming attractive candidates for therapeutic intervention by small drug-like molecules. IDPs are challenging targets because they exist as ensembles of structures, thereby making them unsuitable for standard rational drug design approaches, which require the knowledge of the three-dimensional structure of the proteins to be drugged. As we review in this chapter, several different small molecule strategies are currently under investigation to target IDPs, including: (i) to stabilise IDPs in their natively disordered states, (ii) to inhibit interactions with ordered or disordered protein partners, and (iii) to induce allosteric inhibition. In this context, biophysical techniques, including in particular nuclear magnetic resonance (NMR) spectroscopy and small-angle X-ray scattering (SAXS) coupled with molecular dynamics simulations and chemoinformatics approaches, are increasingly used to characterize the structural ensembles of IDPs and the specific interactions that they make with their binding partners. By analysing the results of recent studies, we describe the main structural features that may render IDPs druggable, and describe techniques that can be used for drug discovery programs focused on IDPs.

Testing three primate species' attentional biases toward preferred and unpreferred foods: Seeing red or high valued food?

Animals navigate complex environments that present both hazards and essential resources. The prioritization of perceptual information that is relevant to their next actions, such as accessing or avoiding different resources, poses a potential challenge to animals, one that can impact survival. While animals' attentional biases toward negatively valanced and threatening stimuli have been explored, parallel biases toward differently valued resources remain understudied. Here, we assessed whether three primate species (chimpanzees [Pan troglodytes], gorillas [Gorilla gorilla gorilla], and Japanese macaques [Macaca fuscata]) prioritized their attention to positively valued resources-preferred foods compared to unpreferred foods. We employed a computerized dot probe attentional bias task in which we presented participants with paired images of their preferred and unpreferred foods in randomized locations (left or right). Latencies to touch the "probe" that replaced either image revealed that all three species responded faster to the probe when it replaced the preferred option (χ²(1) = 284.50, SE² = .03, p < .001). The uniformity of the primates' responses hints that a propensity to prioritize highly preferred items is rooted in these primates' evolutionary past, one that may serve as a mechanism to rapidly detect and locate resources such as highly valued foods. Future research will help disentangle the role that color plays in these biases. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Tinospora cordifolia ameliorates paclitaxel-induced neuropathic pain in albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has been used in the management of sciatica pain and diabetic neuropathy. AIM: The study has been designed to evaluate the antinociceptive potential of various extracts of T. cordifolia stem in Paclitaxel (PT)-generated neuropathic pain model in albino rats and explore its possible mechanism employing molecular docking studies. METHODS: Stems of T. cordifolia were shade dried, grinded in fine powder, and extracted separately with different solvents viz. ethanol, water & hydro-alcoholic and characterized using LCMS/MS. The antinociceptive property of T. cordifolia stem (200 and 400 mg/kg) was examined in albino rats using a PT-induced neuropathic pain model. Further, the effect of these extracts was also observed using different behavioral assays viz. cold allodynia, mechanical hyperalgesia (pin-prick test), locomotor activity test, walking track test, and Sciatic Functional Index (SFI) in rats. Tissue lysate of the sciatic nerve was used to determine various biochemical markers such as GSH, SOD, TBARS, tissue protein, and nitrite. Further to explore the possible mechanism of action, the most abundant and therapeutically active compounds available in aqueous extract were analyzed for binding affinity towards soluble epoxide hydrolase (sEH) enzyme (PDB ID: 3wk4) employing molecular docking studies. RESULTS: The results of the LCMS/MS study of different extracts of T. cordifolia indicated presence of alkaloids, glycosides, terpenoids, sterols and sugars such as amritoside A, tinocordin, magnoflorine, N-methylcoclaurine, coridine, 20ß-hydroxyecdysone and menaquinone-7 palmatin, cordifolioside A and tinosporine etc. Among all the three extracts, the hydroalcoholic extract (400 mg/kg) showed the highest response followed by aqueous and ethanolic extracts as evident in in vivo behavioral and biochemical evaluations. Furthermore, docking studies also exposed that these compounds viz. N-methylcoclaurine tinosporin, palmatine, tinocordin, 20ß-hydroxyecdysone, and coridine exhibited well to excellent affinity towards target sEH protein. CONCLUSION: T. cordifolia stem could alleviate neuropathic pain via soluble epoxide hydrolase inhibitory activity.

Prenatal ontogeny of the dopamine-dependent neurobehavioral phenotype in Pitx3-deficient mice.

Mouse models with prenatal alterations in dopaminergic functioning can provide new opportunities to identify fetal behavioral abnormalities and the underlying neural substrates dependent on dopamine. In this study, we tested the hypothesis that prenatal loss of nigrostriatal function is associated with fetal akinesia, or difficulty initiating movement. Specific behaviors were analysed in fetal offspring derived from pregnant Pitx3(ak) /2J and C57BL/6J dams on the last 4 days before birth (E15-18 of a 19-day gestation). Using digital videography, we analysed: (i) behavioral state, by quantification of high- and low-amplitude movements, (ii) interlimb movement synchrony, a measure of the temporal relationship between spontaneous movements of limb pairs, (iii) facial wiping, a characteristic response to perioral tactile stimulation similar to the defensive response in human infants, and (iv) oral grasp of a non-nutritive nipple, a component of suckling in the human infant. Pitx3 mutants showed a selective decrease in interlimb movement synchrony rates at the shortest (0.1 s) temporal interval coupled with significantly increased latencies to exhibit facial wiping and oral grasp. Collectively, our findings provide evidence that the primary fetal neurobehavioral deficit of the Pitx3 mutation is akinesia related to nigrostriatal damage. Other findings of particular interest were the differences in neurobehavioral functioning between C57BL/6J and Pitx3 heterozygous subjects, suggesting the two groups are not equivalent controls. These results further suggest that fetal neurobehavioral assessments are sensitive indicators of emerging neural dysfunction, and may have utility for prenatal diagnosis.

Power and reduced temporal discounting.

Decision makers generally feel disconnected from their future selves, an experience that leads them to prefer smaller immediate gains to larger future gains. This pervasive tendency is known as temporal discounting, and researchers across disciplines are interested in understanding how to overcome it. Following recent advances in the power literature, we suggest that the experience of power enhances one's connection with the future self, which in turn results in reduced temporal discounting. In Study 1, we found that participants assigned to high-power roles were less likely than participants assigned to low-power roles to display temporal discounting. In Studies 2 and 3, priming power reduced temporal discounting in monetary and nonmonetary tasks, and, further, connection with the future self mediated the relation between power and reduced discounting. In Study 4, experiencing a general sense of power in the workplace predicted actual lifetime savings. These results have important implications for future research.

Effect of gamma radiation on microbial safety and nutritional quality of kachri (Cucumis callosus).

Fresh dried and old (6-12 months) dried kachri (Cucumis callosus) were treated with 0, 2.5, 5 and 7 kGy of gamma radiation in a cobalt 60 gamma cell (GC-1200). The irradiated samples of kachri were stored at room temperature (28 ± 2 °C). Total bacterial count and nutrient composition were evaluated immediately after irradiation and at regular intervals of 1 month during 3 months of storage. Results indicated that gamma radiation reduced the total bacterial counts of dried samples of both fresh and old dried kachri. Dose of 5.0 kGy was sufficient to eliminate total bacterial count and there was no microbial growth in 5.0 kGy irradiated samples during the storage period. No significant differences were observed in the proximate composition of both types of kachri at all irradiation doses. It was concluded that irradiation treatments of kachri improves keeping quality of both freshly dried and old dried Kachri.

Molecular signaling in cancer stem cells of tongue squamous cell carcinoma: Therapeutic implications and challenges.

Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates. Amongst oral cavity cancers, tongue carcinoma is a very common and aggressive oral cavity carcinoma. Despite the implementation of a multimodality treatment regime including surgical intervention, chemo-radiation as well as targeted therapy, tongue carcinoma shows a poor overall 5-year survival pattern, which is attributed to therapy resistance and recurrence of the disease. The presence of a rare population, i.e., cancer stem cells (CSCs) within the tumor, are involved in therapy resistance, recurrence, and distant metastasis that results in poor survival patterns. Therapeutic agents targeting CSCs have been in clinical trials, although they are unable to reach into therapy stage which is due to their failure in trials. A more detailed understanding of the CSCs is essential for identifying efficient targets. Molecular signaling pathways, which are differentially regulated in the CSCs, are one of the promising targets to manipulate the CSCs that would provide an improved outcome. In this review, we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.

Perspectives From Urban WIC-Eligible Caregivers to Improve Produce Access.

OBJECTIVES: The Farmer's Market Nutrition Program (FMNP) provides fresh, locally grown fruits and vegetables (FV) to eligible participants in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). However, redemption of FMNP benefits remains low. This qualitative study explores facilitators and barriers to produce access and FMNP redemption for caregivers of WIC-eligible children in Philadelphia during the COVID-19 pandemic. METHODS: We conducted semistructured phone interviews with caregivers between August and December 2020 to understand experiences with produce access and programming preferences to increase benefit redemption and produce consumption. We used content analysis with constant comparison with code interviews inductively and identified emerging themes through an iterative process. RESULTS: Participants (n = 30) wanted their children to eat more produce but described barriers to produce access, including limited availability, higher cost, and limited time. The Supplemental Nutrition Assistance Program and WIC benefits improved the ability to purchase produce, but difficulties with electronic benefit transfer and pandemic-related office closures limited use of WIC benefits. Similarly, lack of convenient market locations and hours prohibited use of FMNP benefits. Caregivers described that an ideal food program would be delivery based, low cost, offer a variety of FV, and provide recipes and educational activities. CONCLUSIONS: WIC-eligible caregivers want their children to eat more produce; however, they face multiple barriers in redeeming their benefits to access fresh produce. Delivery-based, low-cost produce programs may lead to increased produce access as well as benefit use. Future study is needed on feasibility and acceptability of produce delivery options among WIC-eligible families.

Aetiology, clinical profile and management outcome of pneumothorax patients: A prospective study from Central India.

Background: Pneumothorax (PT) is defined as the presence of air in the pleural cavity. Primary spontaneous pneumothorax (PSP) arises in an otherwise healthy person without any underlying lung disease. PSP occurs in people aged 20 to 30 years, with a peak incidence in the early twenties. The recurrence rate in spontaneous PT patients is approximately 10%-20%. In the present study, 50 cases of spontaneous PT were undertaken with an aim to analyse aetiology, clinical profile and management outcome of PT patients. Materials and Methods: The present study was conducted for a period of 12 months, among 50 patients presenting with unilateral PT. The therapeutic interventions were indicated when there was a loss of volume of lungs of 32% or more, and this loss of volume was calculated using Collins method. The association between the side of PT, smoking status and size of PT were found using the Chi-square test, and the association between variables were considered significant if the P value was <0.05. Results: In the present study, the male patients were 92.0% and only 8.0% of patients were females. The further history-taking of patients had shown that the mode of onset of PT was sudden in 72.0% of patients. Although the success rate of Intracth procedure was lower in comparison with the intercoastal drainage (ICD) procedure, the complication rate of Intracath was lower when compared with extensive subcutaneous. Conclusion: PSP is less common than secondary spontaneous PT. Smoking is an independent risk factor for PT, and it delays its resorbtion.

The Real DAPSI: A Real-World Retrospective Study on Assessing the Efficacy and Safety of a Fixed-Dose Combination of Dapagliflozin and Sitagliptin in the Indian Population.

Introduction Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting millions of individuals worldwide. Effective management of T2DM is crucial to prevent complications. Dapagliflozin and sitagliptin are oral anti-diabetic agents that have been shown to provide synergistic effects in controlling blood glucose levels. However, there is limited data on the efficacy and safety of the dapagliflozin-sitagliptin fixed-dose combination (FDC) in the Indian population. This study aimed to evaluate the real-world effectiveness and safety of the dapagliflozin-sitagliptin FDC in the Indian population. Methods This was a retrospective study conducted at healthcare centers in India. The study included patients with T2DM who were prescribed a FDC of dapagliflozin and sitagliptin. Data were collected from the medical health records of patients, including demographics, baseline glycated hemoglobin (HbA1c), blood glucose levels, BMI, blood pressure, and adverse events. The primary outcome was the change in HbA1c, postprandial plasma glucose (PPG), and fasting plasma glucose (FPG) from baseline to 12 weeks after treatment initiation. Results A total of 358 patients were included in the study, with a mean age of 56.2 years. The majority of the patients were male (68.2%), and the mean baseline HbA1c was 8.9 ± 0.87%. After 12 weeks of treatment with dapagliflozin and sitagliptin, there was a significant reduction in HbA1c levels from 8.9 to 7.2 (p <0.0001). There was also a significant reduction in fasting blood glucose levels from 178.8 to 124.0 (p <0.0001) and postprandial blood glucose levels from 273.9 to 176.0 (p <0.0001). There were no serious adverse events reported during the study period. Conclusion The FDC of dapagliflozin and sitagliptin is effective and safe in reducing blood glucose levels and BMI in the Indian population with T2DM. This real-world retrospective study provides valuable insights into the clinical effectiveness and safety of dapagliflozin-sitagliptin FDC in the Indian population. These findings highlight the potential benefits of this combination therapy in managing T2DM and pave the way for optimized treatment strategies and improved patient outcomes in the Indian healthcare landscape. Clinicians may consider dapagliflozin-sitagliptin FDC as a viable treatment option for T2DM patients.

Pediatric Resident Perspectives on Long-Acting Reversible Contraception Training: A Cross-Sectional Survey of Accreditation Council for Graduate Medical Education Trainees.

PURPOSE: Although pediatricians are primary care providers for most adolescents, pediatric residents receive limited training on long-acting reversible contraceptive (LARC) methods. This study aimed to characterize pediatric resident comfort with placing contraceptive implants and intrauterine devices (IUDs) and assess pediatric resident interest in obtaining this training. METHODS: Pediatric residents in the United States were invited to participate in a survey assessing comfort with LARC methods and interest in LARC training during pediatric residency. Bivariate comparisons used Chi-square and Wilcoxon rank sum testing. Multivariate logistic regression was used to assess associations between primary outcomes and covariates including geographic region, training level, and career plans. RESULTS: Six hundred twenty seven pediatric residents across the United States completed the survey. Participants were predominantly female (68.4%, n = 429), self-identified their race as White (66.1%, n = 412), and anticipated a career in a subspecialty other than Adolescent Medicine (53.0%, n = 326). Most residents were confident counseling patients on the risks and benefits, side effects, and effective use of contraceptive implants (55.6%, n = 344) and both hormonal and nonhormonal IUDs (53.0%, n = 324). Few residents reported comfort with inserting contraceptive implants (13.6%, n = 84) or IUDs (6.3%, n = 39), with most of these respondents having learned these skills as a medical student. Most participants believed that residents should receive training on insertion of contraceptive implants (72.3%, n = 447) and IUDs (62.5%, n = 374). DISCUSSION: Although most pediatric residents believe LARC training should be a component of pediatric residency training, few pediatric residents are comfortable with provision of this care.