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Background Self-management is an essential component of prevention and treatment of type 2 diabetes. Social and family support has been shown to influence self-management behaviors as well as glycemic control and complications. This study was conducted to assess whether diabetes family support improves diabetes self-management and glycemic control in a typical urban population in India. Methods A cross-sectional study using a questionnaire that had items from the Summary of Diabetes Self Care Activities Scale (SDSCA), the Diabetes Family Behavior Checklist (DFBC) and some sociodemographic and diabetes related clinical data was conducted. The participants were consecutively sampled from the diabetes outpatient department in a tertiary care hospital in Chennai, south India. Results A total of 200 consecutive patients from the diabetes outpatient department were interviewed. Diabetes self-management practices were good with respect to avoiding fatty foods and carbohydrates and undergoing regular blood testing for glucose. But the self-management with respect to exercise and foot related care was rare. It was observed that a vast majority of the patients did not report receiving any support from their families. However, in the small proportion who did receive good family support, there is an association between diabetes self-management and diabetes family support (β = 0.527; p  = 0.015). Further, the path model showed that there is a positive statistically significant association between family support score and the diabetes self-management score (β = 0.254, p  < 0.001). However, the negative association between the diabetes self-management score and the mean plasma glucose did not reach statistical significance (β = − 46.378, p  = 0.082). Conclusions In the urban south Indian setting, family support was significantly associated with better self-management activities, but better self-management did not reflect as better glycaemic control.

Peripheral blood mononuclear cells and platelets have long been recognized as having the potential to act as sensitive markers for mitochondrial dysfunction in a broad range of pathological conditions. However, the bioenergetic function of these cells has not been examined from the same donors, yet this is important for the selection of cell types for translational studies. Here, we demonstrate the measurement of cellular bioenergetics in isolated human monocytes, lymphocytes, and platelets, including the oxidative burst from neutrophils and monocytes from individual donors. With the exception of neutrophils, all cell types tested exhibited oxygen consumption that could be ascribed to oxidative phosphorylation with each having a distinct bioenergetic profile and distribution of respiratory chain proteins. In marked contrast, neutrophils were essentially unresponsive to mitochondrial respiratory inhibitors indicating that they have a minimal requirement for oxidative phosphorylation. In monocytes and neutrophils, we demonstrate the stimulation of the oxidative burst using phorbol 12-myristate 13-acetate and its validation in normal human subjects. Taken together, these data suggest that selection of cell type from blood cells is critical for assessing bioenergetic dysfunction and redox biology in translational research.

Platelet thrombus formation includes several integrated processes involving aggregation, secretion of granules, release of arachidonic acid and clot retraction, but it is not clear which metabolic fuels are required to support these events. We hypothesized that there is flexibility in the fuels that can be utilized to serve the energetic and metabolic needs for resting and thrombin-dependent platelet aggregation. Using platelets from healthy human donors, we found that there was a rapid thrombin-dependent increase in oxidative phosphorylation which required both glutamine and fatty acids but not glucose. Inhibition of fatty acid oxidation or glutamine utilization could be compensated for by increased glycolytic flux. No evidence for significant mitochondrial dysfunction was found, and ATP/ADP ratios were maintained following the addition of thrombin, indicating the presence of functional and active mitochondrial oxidative phosphorylation during the early stages of aggregation. Interestingly, inhibition of fatty acid oxidation and glutaminolysis alone or in combination is not sufficient to prevent platelet aggregation, due to compensation from glycolysis, whereas inhibitors of glycolysis inhibited aggregation approximately 50%. The combined effects of inhibitors of glycolysis and oxidative phosphorylation were synergistic in the inhibition of platelet aggregation. In summary, both glycolysis and oxidative phosphorylation contribute to platelet metabolism in the resting and activated state, with fatty acid oxidation and to a smaller extent glutaminolysis contributing to the increased energy demand.

Background: Preinduction cervical ripening in previous caesarean pregnancy is limited to intracervical Foley catheter. This study is aimed at finding the vaginal birth rates, improvement of Bishop score, and safety of osmotic dilator (Dilapan‐S) among women with previous caesarean pregnancy. Methods: We conducted this single‐group clinical study after the approval of the institute ethics committee, clinical trial registration, and obtaining informed consent. We recruited women above 18 years with a prior caesarean section at term and a Bishop score of less than 6 by systematic random sampling prospectively. The first or second author inserted two to a maximum of five osmotic dilators (Dilapan‐S) in the cervical canal. After 24 h, we removed Dilapan and induced labour with a low‐dose oxytocin regimen up to a maximum dose of 24 mIU/min. We assessed the improvement of the Bishop score and vaginal birth rates for efficacy and safety concerns like bleeding, fragmentation, displacement, infections, and scar dehiscence. Results: Eighty‐two women completed the study. The Bishop score significantly improved from a mean of 2.6 before to 5.3 after Dilapan. Three opted for a caesarean section after Dilapan removal and refused oxytocin infusion. Seventy‐nine women completed the trial of labour. Forty‐one (52%) achieved active labour (52%). Twenty‐seven delivered vaginally, and 52 required emergency caesarean section (34% vaginal birth rate; 18 spontaneous, nine instrumental, four with forceps, and five with vacuum). None had entrapment, fragmentation, or upward displacement of Dilapan. Two women had scar dehiscence, and one had a traumatic postpartum haemorrhage. There was no maternal or perinatal mortality. Conclusions: We conclude that the hygroscopic dilator Dilapan effectively ripens the cervix before labour induction in women with a previous caesarean scar. They are safe, but more extensive studies are needed to evaluate scar‐related complications during labour. Trial Registration : Clinical Trial Registry of India: CTRI/2019/03/017927

Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in a number of organs, including the lungs 1 . Cellular metabolism regulates tissue repair and remodelling responses to injury 2 – 4 . AMPK is a critical sensor of cellular bioenergetics and controls the switch from anabolic to catabolic metabolism 5 . However, the role of AMPK in fibrosis is not well understood. Here, we demonstrate that in humans with idiopathic pulmonary fibrosis (IPF) and in an experimental mouse model of lung fibrosis, AMPK activity is lower in fibrotic regions associated with metabolically active and apoptosis-resistant myofibroblasts. Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis. In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner. These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts. Metformin reverses established lung fibrosis in a bleomycin model in mice.

Rosai-Dorfman disease (RDD)/sinus lymphohistiocytosis is a rare benign lymphoproliferative disorder. Only 25% show extra-nodal manifestation, only 5% are seen involving the CNS, with intraventricular manifestation rarely reported. Our aim was to highlight important imaging features which would be useful in considering this entity as one of the differentials while encountering this rare entity. Intraventricular Rosai-Dorfman disease is a rare entity. Imaging features of T2 hypointense homogenously enhancing lesion with blooming on GRE, without features of calcification or hemorrhage, may be helpful in prompting adequate histopathologic evaluation.

Triple‐therapy regimens involving Pregabalin or Gabapentin with nortriptyline and Methylcobalamin have been shown to be efficacious in treating neuropathic pain in clinical trials. This study aims to compare the clinical effectiveness and treatment satisfaction of two triple‐therapy regimens in treating neuropathic pain in a real‐world setting. This prospective, single‐center, observational study compared the efficacy, safety, and treatment satisfaction of triple therapy in Pregabalin triple therapy versus Gabapentin triple therapy for patients with neuropathic pain. The primary outcome measured the reduction in mean Self‐Administered Leeds Assessment of Neuropathic Symptoms and Signs pain score value from the baseline to 12 weeks posttreatment. The secondary outcome measured the treatment satisfaction for both therapies using the Treatment Satisfaction Questionnaire for Medication version 1.4. Of 264 patients who received either treatment group, during the third follow‐up, it became evident that Group A Pregabalin triple therapy yielded a significantly more substantial reduction in neuropathic pain (60.61%) when compared to Group B Gabapentin triple therapy (12.88%). Furthermore, patients expressed markedly higher levels of satisfaction and convenience with the Pregabalin treatment (p ≤ 0.001). Our study's findings, encompassing both clinical effectiveness and treatment satisfaction, unequivocally demonstrate that Group A surpasses Group B in ameliorating neuropathic symptoms and signs. Pregabalin is a more effective and convenient treatment for neuropathic pain than Gabapentin, with no significant difference in side effects. Clinicians should consider Pregabalin as a first‐line treatment option for neuropathic pain, especially for patients not responding to Gabapentin or who seek a more convenient option. This study compared the clinical effectiveness and treatment satisfaction of Pregabalin and Gabapentin triple therapy for neuropathic pain in a real‐world setting. The primary outcome measured the reduction in mean Self‐Administered Leeds Assessment of Neuropathic Symptoms and Signs pain score value from baseline to 12 weeks posttreatment. The secondary outcome measured treatment satisfaction for both therapies using the Treatment Satisfaction Questionnaire for Medication version 1.4. The study found that Group A yielded a significantly more substantial reduction in neuropathic pain (60.61%) compared to Group B (12.88%). Patients expressed higher levels of satisfaction and convenience with the Pregabalin treatment (p < 0.001). The findings demonstrate that Group A surpasses Group B in ameliorating neuropathic symptoms and signs, and Pregabalin is a more effective and convenient treatment for neuropathic pain than Gabapentin, with no significant difference in side effects. Clinicians should consider Pregabalin as a first‐line treatment option for neuropathic pain, especially for patients not responding to Gabapentin or seeking a more convenient option.

Isolated Fallopian tube torsion (IFTT) is a rare entity with utmost important gynecological emergency with difficult preoperative diagnosis. Our aim is to analyze the clinical presentation, risk factors, and management of IFTT. We retrospectively analyzed all patients with intraoperative diagnosis of IFTT in our endogynecological department over a time period of 3 years and 6 months (January 2015-June 2018) in a tertiary level laparoscopic center. The clinical profile of the patients was analyzed and the results formulated. Statistical analysis was done by SPSS system, Version 15.00 (SPSS Inc., Chicago). A total 17 cases were diagnosed with IFTT with or without pathology. The mean age was 28.07 ± 11.3 years. Lower abdominal pain was the most common symptom (88%). About 47% had a history of tubal ligation. Salpingectomy was done in the majority of the patients (82.3%). Detorsion and preservation of the tube was possible in 17.6% of the cases. High index of suspicion is needed to diagnose this rare cause of acute abdomen. Hence, an early intervention can enhance the salvageability of the affected tubes which has a positive impact on the fertility status of the patients. Tubal preservation is the preferred procedure of choice whenever feasible.

CHIP (carboxyl terminus of heat shock 70-interacting protein) has long been recognized as an active member of the cellular protein quality control system given the ability of CHIP to function as both a co-chaperone and ubiquitin ligase. We discovered a genetic disease, now known as spinocerebellar autosomal recessive 16 (SCAR16), resulting from a coding mutation that caused a loss of CHIP ubiquitin ligase function. The initial mutation describing SCAR16 was a missense mutation in the ubiquitin ligase domain of CHIP (p.T246M). Using multiple biophysical and cellular approaches, we demonstrated that T246M mutation results in structural disorganization and misfolding of the CHIP U-box domain, promoting oligomerization, and increased proteasome-dependent turnover. CHIP-T246M has no ligase activity, but maintains interactions with chaperones and chaperone-related functions. To establish preclinical models of SCAR16, we engineered T246M at the endogenous locus in both mice and rats. Animals homozygous for T246M had both cognitive and motor cerebellar dysfunction distinct from those observed in the CHIP null animal model, as well as deficits in learning and memory, reflective of the cognitive deficits reported in SCAR16 patients. We conclude that the T246M mutation is not equivalent to the total loss of CHIP, supporting the concept that disease-causing CHIP mutations have different biophysical and functional repercussions on CHIP function that may directly correlate to the spectrum of clinical phenotypes observed in SCAR16 patients. Our findings both further expand our basic understanding of CHIP biology and provide meaningful mechanistic insight underlying the molecular drivers of SCAR16 disease pathology, which may be used to inform the development of novel therapeutics for this devastating disease.

ObjectiveExamine sensory function of the upper airway in four groups of subjects recruited from the World Trade Centre General Responder Cohort (WTCGRC), with/without obstructive sleep apnoea (OSA), and with/without chronic rhinosinusitis (CRS).MethodsUpper airway sensory function was determined using 2-point discrimination (2-PD) and vibration threshold (VT) in 163 WTCGRC subjects with both OSA and CRS (cases), OSA or CRS alone and without OSA or CRS (controls). Presence of OSA was determined from clinical sleep studies or home sleep testing. Presence of CRS was determined by nasal symptom questionnaire. The relationship between the presence of OSA and CRS and upper airway sensory impairment was assessed using linear regression analysis with each of 2PD and VT sensory threshold values as the dependent variable; OSA, CRS and their interaction were the independent variables. Age, gender and body mass index were covariates in the statistical model. The primary analysis was comparison of OSA+CRS versus controls (no OSA and no CRS) evaluated by linear contrasts.ResultsThere were no differences in 2-PD or VT in those with OSA+CRS, OSA and CRS alone or controls. However, both 2-PD and VT were significantly higher in the WTCGRC controls compared with values seen in historical controls using the same methodology (median 2-PD 13.0; CI (11.0 to 13.5) vs 10.5; CI (8 to 11); VT: mean±SEM (9.3±0.6 vs 2.2±0.1)).ConclusionWhile no differences were found in upper airway sensation between cases of OSA and CRS versus controls in the WTGRC population, there was evidence of impaired upper airway sensation in the WTGRC overall.