Genome-wide gene expression responses to experimental manipulation of Saccharomyces cerevisiae repressor activator protein 1 (Rap1) expression level.

Precise regulation of transcription in gene expression is critical for all aspects of normal organism form, fitness, and function and even minor alterations in the level, location, and timing of gene expression can result in phenotypic variation within and between species including evolutionary innovations and human disease states. Eukaryotic transcription is regulated by a complex interplay of multiple factors working both at a physical and molecular levels influencing this process. In Saccharomyces cerevisiae, the TF with the greatest number of putative regulatory targets is the essential gene Repressor Activator Protein 1 (RAP1). While much is known about the roles of Rap1 in gene regulation and numerous cellular processes, the response of Rap1 target genes to systematic titration of RAP1 expression level remains unknown. To fill this knowledge gap, we used a strain with a tetracycline-titratable promoter replacing wild-type regulatory sequences of RAP1 to systematically reduce the expression level of RAP1 and followed this with RNA sequencing (RNA-seq) to measure genome-wide gene expression responses. Previous research indicated that Rap1 plays a significant regulatory role in particular groups of genes including telomere-proximal genes, homothallic mating (HM) loci, glycolytic genes, DNA repair genes, and ribosomal protein genes; therefore, we focused our analyses on these groups and downstream targets to determine how they respond to reductions in RAP1 expression level. Overall, despite being known as both an activator and as a repressor of its target genes, we found that Rap1 acts as an activator for more target genes than as a repressor. Additionally, we found that Rap1 functions as an activator of ribosomal protein genes and a repressor for HM loci genes consistent with predictions from the literature. Unexpectedly, we found that Rap1 functions as a repressor of glycolytic enzyme genes contrary to prior reports of it having the opposite effect. We also compared the expression of RAP1 to five different genes related to DNA repair pathway and found that decreasing RAP1 downregulated four of those five genes. Finally, we found no effect of RAP1 depletion on telomere-proximal genes despite its functioning to silence telomeric repeat-containing RNAs. Together our results enrich our understanding of this important transcriptional regulator.

Psychological health of postmenopausal women: a bibliometric analysis in the recent decade.

The aim of this study is to analyze the publication trends on the psychological health of postmenopausal women by performing a bibliometric and visualization analysis that can be used as a foundation for understanding current and future research plans. Publications were retrieved from Dimensions database from 2012 to June 2022. VOSviewer software was used for data mining and visualization. A total of 1718 papers were selected by keyword search and delimiting criteria. To evaluate the productive nations, authors, journals, articles and frequent joint citations, citation analysis, author keyword co-occurrence analysis, co-authorship analysis and co-citation analysis were performed. Results depict that the USA contributed the most papers (n = 457). Maximum articles (n = 192) were published in 2021. The highest number of articles are published in Menopause: The Journal of the North American Menopause Society and Climacteric: The Journal of the International Menopause Society. Out of the top 10 contributing organizations in the field, six organizations were from the USA. R. Nappi of Italy is the most productive author with 20 articles and 1138 citations. From the point of average citations per article, H. Joffe has the highest score (71.5). The data reported in this analysis contribute to discussions about the development, growth and current state of psychological health of postmenopausal women as well as its impact. These findings offer helpful guidance for researchers in choosing their potential fields of study and integrating different approaches to solve complicated issues, finding potential co-authors and choosing the right institutions for supporting academic studies or collaborative research.

Comparative Evaluation of Various Lens and Ring Flash Combination for Intraoral Photography.

BACKGROUND: Extraoral and intraoral dental photographs serve as preoperative records and document the entire treatment. Correctly composed orthodontic photographs are crucial for remote diagnosis and may serve as a bulwark against medicolegal challenges. MATERIALS AND METHODS: In this prospective study, intraoral frontal photographs of patients with ideal occlusion were taken using two types of lenses (EF-S 18-55 mm f/3.5-5.6 IS STM lens (Canon, Tokyo, JP), SP 90 mm F/2.8 MACRO VC lens (Model F017 Tamron, NY, USA)) and two different ring flash systems (Meike FC-100 Macro Ring LED Light (Meike, China), Macro Ring flash Lite YN-14EX (Yongnuo digital, China)). The combination of lens and flash used was grouped into four groups. Twenty-eight intraoral photographs of patients were taken. An image quality assessment survey was distributed among two groups - 50 orthodontists and 50 other dental specialists. RESULTS: The participants were asked to assess all the intraoral images and subjectively score them on a scale of one to ten, with one being very poor and ten being excellent, considering the sharpness, color, brightness, contrast, and overall quality of the image. The general dentists rated the images taken with a 90-mm macro lens and ring flash as the best quality photographs. Images obtained using an 18-55 mm lens and ring LED received significantly lesser scores and were graded good by dentists. CONCLUSION: This combination of lens and flash may prove a valuable investment in the long-term aiding in excellent dental images for diagnosis and treatment monitoring.

UNVEILING THE COMPLEX ROLE OF NF-ΚB IN ALZHEIMER'S DISEASE: INSIGHTS INTO BRAIN INFLAMMATION AND POTENTIAL THERAPEUTIC TARGETS.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and dementia. One of the major pathologies underlying AD is chronic neuroinflammation mediated by microglia and astrocytes in the brain. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathway is a key regulator of inflammation and has been implicated in the neuroinflammatory processes associated with AD. This review comprehensively summarizes current findings on the complex role of NF-κB signalling in AD pathogenesis. The canonical and non-canonical NF-κB activation pathways are described, along with evidence from human studies and animal models demonstrating increased NF-κB activity in AD brains. The deleterious effects of NF-κB-mediated neuroinflammation are discussed, including the upregulation of inflammatory cytokines, chemokines, and enzymes that exacerbate neuronal damage over time. Targeting the NF-κB pathway is proposed as a promising therapeutic approach to dampen neuroinflammation in AD. Preclinical studies utilizing genetic or pharmacological inhibition of NF-κB are reviewed, and key challenges in translating these findings to clinical applications are analyzed. Overall, this review unveils the multifaceted contributions of NF-κB signalling to AD neuropathology and highlights anti-neuroinflammatory NF-κB modulation as a potential avenue for future AD treatments. Further research is warranted to fully elucidate the complex interactions between NF-κB and AD pathogenesis.

Prospective machine learning CT quantitative evaluation of idiopathic pulmonary fibrosis in patients undergoing anti-fibrotic treatment using low- and ultra-low-dose CT.

AIM: To compare the machine learning computed tomography (CT) quantification tool, Computer-Aided Lung Informatics for Pathology Evaluation and Ratings (CALIPER) to pulmonary function testing (PFT) in assessing idiopathic pulmonary fibrosis (IPF) for patients undergoing treatment and determine the effects of limited (LD) and ultra-low dose (ULD) CT on CALIPER performance. MATERIALS AND METHODS: Thirty-eight IPF patients underwent PFT and standard, LD, and ULD CT. CALIPER classified each CT voxel into either vessel-related structures (VRS), normal, reticular (R), honeycomb (HC) or ground-glass (GG) features. CALIPER-derived interstitial lung disease (ILD) extent represented the sum of GG, R and HC values. Repeated-measures correlation coefficient (ρrm) and 95% confidence interval (CI) evaluated CALIPER features correlation with PFT. Lin's concordance correlation coefficient (CCC) assessed concordance of CALIPER parameters across different CT dosages. RESULTS: Twenty patients completed 12 months of follow-up. CALIPER ILD correlated significantly with percent predicted (%) forced vital capacity (FVC) and forced expiratory volume in 1 second (%FEV1; p=0.004, ρrm -0.343, 95% CI [-0.547, -0.108] and 0.008, -0.321, [-0.518, -0.07], respectively). VRS significantly correlated with %FVC and %FEV1 (p=0.000, ρrm -0.491, 95% CI [-0.685, -0.251] and -0.478, 0.000, [-0.653, -0.231], respectively). There was near perfect LD and moderate ULD concordance with standard dose CT for both ILD (CCC 0.995, 95% CI 0.988-0.999 and 0.9, 0.795-0.983, respectively) and VRS (CCC 0.989, 95% CI 0.963-0.997 and 0.915, 0.806-0.956, respectively). CONCLUSIONS: CALIPER parameters correlate well with PFTs for evaluation of IPF in patients undergoing anti-fibrotic treatment without being influenced by dose variation. CALIPER may serve as a robust, objective adjunct to PFTs in assessing anti-fibrotic treatment related changes.

Rationale, study design and methodology of the LANDMARC trial: a 3-year, pan-India, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

AIM: India contributes towards a large part of the worldwide epidemic of diabetes and its associated complications. However, there are limited longitudinal studies available in India to understand the occurrence of diabetes complications over time. This pan-India longitudinal study was initiated to assess the real-world outcomes of diabetes across the country. METHODS: The LANDMARC study is the first prospective, multicentre, longitudinal, observational study investigating a large cohort of people with type 2 diabetes mellitus across India over a period of 3 years. The primary objective of this ongoing study is to determine the proportion of people developing macrovascular diabetes complications over the duration of the study (36 months ± 45 days) distributed over seven visits; the secondary objective is to evaluate microvascular diabetes complications, glycaemic control and time-to-treatment adaptation or intensification. Overall, 6300 participants (aged 25-60 years) diagnosed with type 2 diabetes for at least 2 years will be included from 450 centres across India. Data will be recorded for baseline demographics, comorbidities, glycaemic measurements, use of anti-hyperglycaemic medications and any cardiovascular or other diabetes-related events occurring during the observational study period. CONCLUSIONS: The LANDMARC study is expected to reveal the trends in complications associated with diabetes, treatment strategies used by physicians, and correlation among treatment, control and complications of diabetes within the Indian context. The findings of this study will help to identify the disease burden, emergence of early-onset complications and dose titration patterns, and eventually develop person-centred care and facilitate public health agencies to invest appropriate resources in the management of diabetes. (Trial Registration No: CTRI/2017/05/008452).

Cardiovascular disease management in people with diabetes outside North America and Western Europe in 2006 and 2015.

AIM: Optimal treatment of cardiovascular disease is essential to decrease mortality among people with diabetes, but information is limited on how actual treatment relates to guidelines. We analysed changes in therapeutic approaches to anti-hypertensive and lipid-lowering medications in people with Type 2 diabetes from 2006 and 2015. METHODS: Summary data from clinical services in seven countries outside North America and Western Europe were collected for 39 684 people. Each site summarized individual-level data from outpatient medical records for 2006 and 2015. Data included: demographic information, blood pressure (BP), total cholesterol levels and percentage of people taking statins, anti-hypertensive medication (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor blockers, thiazide diuretics) and antiplatelet drugs. RESULTS: From 2006 to 2015, mean cholesterol levels decreased in six of eight sites (range: -0.5 to -0.2), whereas the proportion with BP levels > 140/90 mmHg increased in seven of eight sites. Decreases in cholesterol paralleled increases in statin use (range: 3.1 to 47.0 percentage points). Overall, utilization of anti-hypertensive medication did not change. However, there was an increase in the use of angiotensin II receptor blockers and a decrease in angiotensin-converting enzyme inhibitors. The percentage of individuals receiving calcium channel blockers and aspirin remained unchanged. CONCLUSIONS: Our findings indicate that control of cholesterol levels improved and coincided with increased use of statins. The percentage of people with BP > 140/90 mmHg was higher in 2015 than in 2006. Hypertension treatment shifted from using angiotensin-converting enzyme inhibitors to angiotensin II receptor blockers. Despite the potentially greater tolerability of angiotensin II receptor blockers, there was no associated improvement in BP levels.

Expert Group Consensus Opinion: Role of Anti-inflammatory Agents in the Management of Type-2 Diabetes (T2D).

Diabetes is a major public health emergency of the 21st century. Results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study have found prevalence of diabetes and prediabetes in India to be as high as 7.3% and 10.3%, respectively with nation-wide projection of 77.2 million people with prediabetes and 69.2 million with diabetes. It is well established that insulin resistance (IR) and islet ß-cell failure are the two major features of T2D Multiple mechanisms including glucotoxicity, lipotoxicity, oxidative stress, endoplasmic reticulum stress, formation of amyloid deposits in the islets, etc. have been hypothesized to participate in the pathology of the disease. In the concluding decade of the last century, numerous studies - prospective and cross-sectional, have confirmed the role of chronic low-grade inflammation as a pathogenetic factor of T2D. It has been shown that increased levels of various inflammatory markers and mediators including fundamental markers like white blood cell count, C-reactive protein (CRP) to the more specific circulating cytokines like, interleukin-6 (IL-6), IL-1ß, plasminogen activator inhibitor-1 (PAI-1), etc. correlate with incident T2D. Based on the robust evidence implying the role of inflammation in T2D pathogenesis, several studies have proven that the proinflammatory cytokines play a central role in the development of microvascular diabetic complications such as nephropathy, retinopathy, and neuropathy. Inflammation in T2D causes accelerated atherosclerosis which predisposes to CVD, the leading cause of mortality in these patients. Recently there is a considerable increase in the interest among the researchers about anti-inflammatory therapies in the setting of chronic disorders such as T2D and CV diseases. In a multi-country study conducted in Asia, approximately 50% of Indian respondents had poor diabetes control. Most patients initially respond to sulfonylurea and/or metformin, and later these agents lose their effectiveness with time. Therapeutic option in patients uncontrolled on two-drug combination therapy is either to add third oral drug or insulin. However, use of insulin is limited due to its high cost and poor compliance. Majority of new treatment options like GLP1 agonists, insulin analogs and SGLT2 inhibitors are costly considering they are still under patent. The thiazolidinedione class of drugs is associated with adverse effects like fluid retention and weight gain that may result in or exacerbate edema and congestive heart failure. Thus there is a need for a safe and inexpensive treatment option for the management of uncontrolled T2D. Considering the role of inflammation in T2D pathogenesis, the drug should not only have antihyperglycemic effects but also reduce inflammatory burden thus reducing the progression and complications of T2D. The current interest is apparently directed towards drugs targeting inflammation acting at different stages of the inflammatory cascade. In the recently published CANTOS study, canakinumab, a selective, high-affinity, fully human monoclonal antibody which inhibits IL-1ß, has no consistent long-term benefits on HbA1c. Other selective inhibitors like anakinra (IL-1 receptor antagonist) and etanercept (TNF inhibitor) too have yielded modest effects on glycemic parameters and insulin sensitivity. However, hydroxychloroquine (HCQ), a broad anti-inflammatory agent has been shown to reduce HbA1c by 0.87%. Hydroxychloroquine (HCQ) is considered as one of the safest disease modifying anti-rheumatic drug, used widely for the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The effect of HCQ in preventing development of diabetes in patients with chronic inflammatory diseases was highlighted in a prospective observational study of 4905 adults with rheumatoid arthritis and no diabetes with 21.5 years of follow-up. Patients who took HCQ for more than 4 years had a significant 77% lower risk of diabetes compared with non users of HCQ (RR, 0.23; 95% CI, 0.11-0.50). Taking cue from this study highlighting the anti-diabetic effect of HCQ, pioneering research studies evaluating these effects of HCQ were conducted in India. In 2014, hydroxychloroquine 400 mg got DCGI approval as an adjunct to diet and exercise to improve glycemic control of patients on metformin, sulfonylurea combination in Type 2 diabetes.

A histological assessment of effects of sucralose on liver of albino rats.

OBJECTIVE OF THE STUDY: Sucralose is an artificial sweetener freely available under different brand names over the counter. This study is aimed at evaluating the histopathological changes in the liver after administration of sub lethal dose of pure sucralose. MATERIALS AND METHODS: Inbred adult Wistar albino rats weighing about 150-200g of either sex, were divided into 6 control rats and 6 experimental rats. Experimental rats were given sucralose orally by gavage in the dose of 3g/kg/day dissolved in distilled water for 30 days whereas Control rats received equal quantity of distilled water by the same route. The animals were anesthetized with anesthetic ether and then perfused with 10% formal saline. Livers were dissected out. Pieces each having thickness 5mm were taken for paraffin sectioning. 5 micron thick sections were cut using a rotary microtome. Hundred slides were made from each liver and stained with hematoxylin and eosin, periodic acid-schiff (PAS) and Masson's trichrome stain. Slides were evaluated for histomorphological changes. RESULTS: Experimental rats showed features of patchy degeneration of hepatocytes along with Kupffer cells hyperplasia, lymphocytic infiltration, sinusoidal dilatation and fibrosis indicating a definite hepatic damage on regular ingestion of sucralose. Sinusoidal width was also found to be increased in experimental animals as compared to controls. CONCLUSION: It is suggestive that sucralose should be taken with caution to avoid hepatic damage. Effects of ingestion of sucralose on human subjects should be investigated further.

CCR6+ Th cells in the cerebrospinal fluid of persons with multiple sclerosis are dominated by pathogenic non-classic Th1 cells and GM-CSF-only-secreting Th cells.

Considerable attention has been given to CCR6+ IL-17-secreting CD4+ T cells (Th17) in the pathology of a number of autoimmune diseases including multiple sclerosis (MS). However, other Th subsets also play important pathogenic roles, including those that secrete IFNγ and GM-CSF. CCR6 expression by Th17 cells allows their migration across the choroid plexus into the cerebrospinal fluid (CSF), where they are involved in the early phase of experimental autoimmune encephalomyelitis (EAE), and in MS these cells are elevated in the CSF during relapses and contain high frequencies of autoreactive cells. However, the relatively low frequency of Th17 cells suggests they cannot by themselves account for the high percentage of CCR6+ cells in MS CSF. Here we identify the dominant CCR6+ T cell subsets in both the blood and CSF as non-classic Th1 cells, including many that secrete GM-CSF, a key encephalitogenic cytokine. In addition, we show that Th cells secreting GM-CSF but not IFNγ or IL-17, a subset termed GM-CSF-only-secreting Th cells, also accumulate in the CSF. Importantly, in MS the proportion of IFNγ- and GM-CSF-secreting T cells expressing CCR6 was significantly enriched in the CSF, and was elevated in MS, suggesting these cells play a pathogenic role in this disease.

Adenosine monophosphate-activated protein kinase-based classification of diabetes pharmacotherapy.

The current classification of both diabetes and antidiabetes medication is complex, preventing a treating physician from choosing the most appropriate treatment for an individual patient, sometimes resulting in patient-drug mismatch. We propose a novel, simple systematic classification of drugs, based on their effect on adenosine monophosphate-activated protein kinase (AMPK). AMPK is the master regular of energy metabolism, an energy sensor, activated when cellular energy levels are low, resulting in activation of catabolic process, and inactivation of anabolic process, having a beneficial effect on glycemia in diabetes. This listing of drugs makes it easier for students and practitioners to analyze drug profiles and match them with patient requirements. It also facilitates choice of rational combinations, with complementary modes of action. Drugs are classified as stimulators, inhibitors, mixed action, possible action, and no action on AMPK activity. Metformin and glitazones are pure stimulators of AMPK. Incretin-based therapies have a mixed action on AMPK. Sulfonylureas either inhibit AMPK or have no effect on AMPK. Glycemic efficacy of alpha-glucosidase inhibitors, sodium glucose co-transporter-2 inhibitor, colesevelam, and bromocriptine may also involve AMPK activation, which warrants further evaluation. Berberine, salicylates, and resveratrol are newer promising agents in the management of diabetes, having well-documented evidence of AMPK stimulation medicated glycemic efficacy. Hence, AMPK-based classification of antidiabetes medications provides a holistic unifying understanding of pharmacotherapy in diabetes. This classification is flexible with a scope for inclusion of promising agents of future.

Ketogenic diet in endocrine disorders: Current perspectives.

Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for "diabesity."

Correlates of psychological care strategies for people with diabetes in the second Diabetes Attitudes, Wishes and Needs (DAWN2(™) ) study.

AIMS: To assess the ways in which healthcare professionals address psychological problems of adults with diabetes in the second Diabetes Attitudes, Wishes and Needs (DAWN2(™) ) study. METHODS: Approximately 120 primary care physicians, 80 diabetes specialists and 80 nurses and dietitians providing diabetes care participated in each of 17 countries (N=4785). Multiple regression analyses were used to evaluate independent statistically significant associations of respondent attributes concerning psychological care strategies, including assessment of diabetes impact on the patient's life, assessment of depression, provision of psychological assessment and support, and coordination with mental health professionals. RESULTS: Psychological care strategies were positively associated with each other but differed by healthcare practice site and discipline; nurses and dietitians were less likely to assess depression than other healthcare professionals, while primary care physicians were less likely to coordinate with mental health specialists or ask patients how diabetes affects their lives. Psychological care was positively associated with healthcare professionals' beliefs that patients need help dealing with emotional issues and that clinical success depends on doing so, and also with level of psychological care training, multidisciplinary team membership and availability of resources for psychological care. There were significant between-country variations in psychological care strategies, before and after adjustment for individual-level factors, and significant country-by-covariate interactions for almost all individual-level factors investigated. CONCLUSIONS: Improvements in training and resources, recognition and assessment of psychological problems, and increased belief in the efficacy of psychological support may enhance healthcare professionals' efforts to address psychological problems in adults with diabetes.

Alternate sunitinib schedules in patients with metastatic renal cell carcinoma.

Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor exhibiting antiangiogenic activity. Sunitinib demonstrated improved outcomes in comparison to interferon-α in a large phase III study of treatment naïve patients with metastatic renal cell carcinoma. Maintaining patients on sunitinib treatment is essential for a sustained disease control as higher exposure to sunitinib has been associated with an improved overall response rate, progression-free survival and overall survival. Various studies have compared the outcomes of patients undergoing sunitinib therapy based on modifications from their standard dose and schedule. Several studies have shown that switching to an alternate schedule with more frequent dose interruptions without affecting dose density over a 6-week cycle is associated with improved outcomes and increased tolerability.

Randomized controlled trial of benzocaine versus placebo spray for pain relief at hysterosalpingogram.

Many women experience pain during hysterosalpingogram (HSG). This prospective, randomized, double-blinded, placebo-controlled study assessed whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, parity, pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic pelvic pain. Median change in pain score from baseline to procedure was 50.6mm (-7.4 to 98.8mm) in the benzocaine group and 70.4mm (19.8 to 100mm) in the placebo group. There was no difference between groups after adjusting for history of dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus placebo groups at 5 min post procedure--median pain score difference -11.1 (-90.1 to 18.5) versus -37.0 (-100 to 1.2)--or at 30 min post procedure. Satisfaction scores did not differ by treatment and did not correlate with pain score during the procedure (rho=0.005). The use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. Many women experience pain during hysterosalpingogram (HSG), which is a test used to evaluate the uterine cavity and fallopian tube. We conducted a prospective, randomized, double-blinded, placebo-controlled study to assess whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, previous pregnancies, pre-procedure oral analgesic use and history of dysmenorrhoea (painful periods) and/or chronic pelvic pain. There was no difference in pain scores or resolution of pain between the two groups. Satisfaction scores did not differ by treatment group and did not correlate with the pain score during the procedure. We conclude that the use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain.

A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea.

AIMS: To evaluate the efficacy and safety of saxagliptin as add-on therapy in adults with type 2 diabetes with inadequate glycaemic control on metformin plus a sulphonylurea. METHODS: In this 24-week, multicentre, randomized, parallel-group, double-blind study, outpatients aged ≥18 years with type 2 diabetes, body mass index ≤40 kg/m(2) and inadequate glycaemic control, received saxagliptin 5 mg or placebo once-daily added to background medication consisting of a stable maximum tolerated dose of metformin plus a sulphonylurea. The primary end point was change in glycated haemoglobin (HbA1c) from baseline to week 24. Safety and tolerability assessments included adverse events (AEs), hypoglycaemia and body weight. RESULTS: A total of 257 patients were randomized, treated and included in the safety analysis (saxagliptin, n = 129; placebo, n = 128); 255 were included in the efficacy analysis (saxagliptin, n = 127; placebo, n = 128). HbA1c reduction was greater with saxagliptin versus placebo [between-group difference in adjusted mean change from baseline, -0.66%; 95% confidence interval (CI), -0.86 to -0.47 (7 mmol/mol, -9.4 to -5.1); p < 0.0001]. The proportion of patients with ≥1 AE was 62.8% with saxagliptin and 71.7% with placebo. In the saxagliptin and placebo groups, rates of reported hypoglycaemia were 10.1 and 6.3%, respectively, and rates of confirmed hypoglycaemia (symptoms + glucose < 2.8 mmol/l) were 1.6 and 0%. Mean change in body weight was 0.2 kg for saxagliptin and -0.6 kg for placebo (p = 0.0272). CONCLUSION: Addition of saxagliptin 5 mg/day in patients inadequately controlled on metformin and sulphonylurea effectively improved glycaemic control and was well tolerated.

Correlation between measures of hypoglycemia and glycemic improvement in sulfonylurea treated patients with type 2 diabetes in India: results from the OBSTACLE hypoglycemia study.

BACKGROUND: This study aimed to assess correlation between measures of hypoglycemia and glycemic control in patients with type 2 diabetes mellitus (T2DM) treated with sulfonylureas. MATERIALS AND METHODS: T2DM patients being initiated on a sulfonylurea (SU) on background of a failing oral antihyperglycemic regimen were followed up for 12 weeks. (HbA1c) was measured at baseline and end of follow-up. Hypoglycemia was assessed using Stanford Hypoglycemia Questionnaire at week 12. RESULTS: Of the total 1069 patients enrolled, 950 were considered evaluable. A weak negative correlation was observed between end of follow-up HbA1c values and hypoglycemia score, using both linear regression analysis (correlation coefficient -0.12; P = 0.0002) and negative binomial regression (ß slope -0.09; P = 0.0010). A similar correlation was also observed between change in HbA1c from baseline and hypoglycemia score (ß slope -0.07; P = 0.0048). Mean HbA1c reduction was lowest (0.65 ± 2.27%) in patients not reporting any hypoglycemia and highest (1.28 ± 2.40%) in patients with hypoglycemia score greater than median of 2 (P = 0.0031). There was no correlation between hypoglycemia frequency and end of follow-up HbA1c values (P = 0.4111). CONCLUSION: With addition of SU on a background of a failing oral anti-hyperglycemic regimen, the extent of glycemic control correlates directly with measures of patient reported hypoglycemia.

Diabetes Attitudes, Wishes and Needs second study (DAWN2™): cross-national benchmarking indicators for family members living with people with diabetes.

AIMS: The second Diabetes Attitudes, Wishes and Needs (DAWN2) study examined the experiences of family members of people with diabetes for benchmarking and identifying unmet needs or areas for improvement to assist family members and those with diabetes to effectively self-manage. METHODS: In total, 2057 family members of people with diabetes participated in an online, telephone or in-person survey designed to assess the impact of diabetes on family life, family support for people with diabetes and educational and community support. RESULTS: Supporting a relative with diabetes was perceived as a burden by 35.3% (range across countries 10.6-61.7%) of respondents. Over half of respondents [51.4% (22.5-76.0%)] rated their quality of life as 'good' or 'very good'. However, distress about the person with diabetes was high, with 61.3% (31.5-86.4%) worried about hypoglycaemia. The impact of diabetes on aspects of life was felt by 51.8% (46.9-58.6%). The greatest negative effect was on emotional well-being [44.6% (31.8-63.0%)], although depression was less common [11.6% (4.2-20.0%)]. Many respondents did not know how to help the person with diabetes [37.1% (17.5-53.0%)] and wanted to be more involved in their care [39.4% (15.5-61.7%)]. Participation in diabetes educational programmes was low [23.1% (9.4-43.3%)], although most of those who participated found them helpful [72.1% (42.1-90.3%)]. CONCLUSIONS: Diabetes has a negative impact on family members of people with diabetes. DAWN2 provides benchmarking indicators of family members' psychosocial needs that will help identify the support required for, and from, them to improve the lives of people with diabetes and their families.