Peroxisome Proliferator-Activated Receptor Agonists: Do They Increase Cardiovascular Risk?

Cardiovascular disease is a major cause of morbidity and mortality among people with type 2 diabetes mellitus. The peroxisome proliferator-activated receptor (PPAR) agonists have a significant role on glucose and fat metabolism. Thiazolidinediones (TZDs) are predominantly PPARγ agonists, and their primary benefit appears to be the prevention of diabetic complications by improving glycemic control and lipid profile. Recently, the cardiovascular safety of rosiglitazone was brought to center stage following meta analyses and the interim analysis of the RECORD trial. Current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. This review article discusses the mechanism of action of PPAR agonists and correlates it with clinical and laboratory outcomes in the published literature. In addition, this review article attempts to discuss some of the molecular mechanisms regarding the association between TZDs therapy and the nontraditional cardiovascular risks

A community based study to determine incidence of cervical cancer and willingness of women to participate in cervical cancer screening program in Navsari, Gujarat, India

Background: Carcinoma of the uterine cervix is a major health problem faced by the Indian women. Regular cervical cytological examination by all sexually active women can prevent the occurrence of carcinoma cervix. Early detection of cervical cancer is possible with Pap smear tests. Methods: Women above 25 years of age, living in study area and want to participate in study were included. Total 2352 women were enrolled in study. House to house visits were conducted in all the village area by using simple random sampling method. Information about cervical cancer was given. Pap test for cervical cancer screening was carried out by gynaecologist. Cytological examination and confirmation was done by pathologists.Results: A total of 3001 women had attended village level IEC session and out that, 2352 (78.4%) women took part in the screening program. Out of these 2352 women, 2007 women (85.3% compliance) had given consent for physical cervical examination and Pap smear. The incidence of cervical cancer was 0.2% on the basis of clinical examination and biopsy.Conclusions: Higher compliance for undergoing vaginal examination and Pap test shows the positive health seeking behaviour of the women but for that, strong IEC and sensitization about the disease must be done to improve the participation. Sensitivity of Pap test was poor and couldn’t find true positive cases

Structural Analyses of Stirling Power Convertor Heater Head for Long-Term Reliability, Durability, and Performance

Deep-space missions require onboard electric power systems with reliable design lifetimes of up to 10 yr and beyond. A high-efficiency Stirling radioisotope power system is a likely candidate for future deep-space missions and Mars rover applications. To ensure ample durability, the structurally critical heater head of the Stirling power convertor has undergone extensive computational analyses of operating temperatures (up to 650 C), stresses, and creep resistance of the thin-walled Inconel 718 bill of material. Durability predictions are presented in terms of the probability of survival. A benchmark structural testing program has commenced to support the analyses. This report presents the current status of durability assessments

Phase-change technologies: from PCRAM to probe-storage to processors

Phase-change materials based on chalcogenide alloys, for example GeSbTe and AgInSbTe, show remarkable properties such as: the ability to be crystallized by pulses in the (hundreds of) femtoseconds region while at the same time withstanding spontaneous crystallization for many years; the ability to be cycled between phases 1012 times or more; the existence of a huge contrast between the refractive index of the phases; the existence of a huge electrical contrast between phases. These remarkable properties make phase-change materials suitable for a wide range of optical and electrical applications, for optical and electrical memories, for optical routers, for optical and electrical processors. In this paper we describe theoretical and experimental investigations of some of the key application areas, with a view to providing insights into the possible future use of phase-change materials

Serotonin-Norepinephrine Reuptake Inhibitors for Pain Control: Premise and Promise

The precise mechanisms of pain perception and transmission in the central nervous system have not been fully elucidated. However, extensive data support a role for the monoamine neurotransmitters, serotonin and norepinephrine, in the modulation of pain. Experiments with animal models of pain indicate that noradrenergic interventions, and to a lesser extent serotonergic interventions, reduce pain-related behavior. This is supported by data from clinical trials in humans in which antidepressants have been shown to reduce pain and functional impairment in central and neuropathic pain conditions. These effects are particularly well-studied in trials with serotonin-norepinephrine reuptake inhibitors (SNRIs), which have provided a useful tool in the clinician’s arsenal, particularly considering the limitations of other classes of pain medications such as opioids, anti-inflammatories, and anticonvulsants (i.e., limited efficacy, safety and tolerability issues). Moreover, painful physical symptoms are frequently comorbid with major psychiatric disorders such as major depressive disorder and anxiety disorders. This paper reviewed and summarized the rationale and potential role of SNRIs for the control of pain including clinical and preclinical background. Currently evidence does not definitely support a role of the SNRIs, while limited data propose a putative promise of SNRIs in the treatment of pain related disorders including fibromyalgia and depressed patients with multiple somatic complaints. More researches are warranted to generalize currently available preliminary evidences

Phase-change technologies: from PCRAM to probe-storage to processors

Phase-change materials based on chalcogenide alloys, for example GeSbTe and AgInSbTe, show remarkable properties such as: the ability to be crystallized by pulses in the (hundreds of) femtoseconds region while at the same time withstanding spontaneous crystallization for many years; the ability to be cycled between phases 1012 times or more; the existence of a huge contrast between the refractive index of the phases; the existence of a huge electrical contrast between phases. These remarkable properties make phase-change materials suitable for a wide range of optical and electrical applications, for optical and electrical memories, for optical routers, for optical and electrical processors. In this paper we describe theoretical and experimental investigations of some of the key application areas, with a view to providing insights into the possible future use of phase-change materials

Positive predictive value of ERBB2 copy number gain by tissue or circulating tumor DNA next-generation sequencing across advanced cancers

BACKGROUND: The correlation of ERBB2 copy number gain (CNG) from tissue or circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) with standard HER2 tissue evaluation is not well understood. MATERIALS AND METHODS: We retrospectively identified patients with ERBB2 CNG on commercial NGS. We described their clinical-pathologic features and calculated the positive predictive value (PPV) of ERBB2 CNG by NGS for HER2-positivity by IHC and FISH testing. RESULTS: 176 patients had NGS revealing an ERBB2 CNG (112 by tumor tissue and 91 by ctDNA). The cancer subtypes with the most cases with ERBB2 CNG by NGS were breast ( CONCLUSIONS: ERBB2 CNG by NGS is detected in numerous malignancies for which HER2 testing is not standard. Detection of ERBB2 CNG by tissue NGS and ctDNA has a high PPV for true HER2-positivity by standard IHC and/or FISH testing in breast cancer

Disproportionate left atrial myopathy in heart failure with preserved ejection fraction among participants of the PROMIS-HFpEF study

Impaired left atrial (LA) function in heart failure with preserved ejection fraction (HFpEF) is associated with adverse outcomes. A subgroup of HFpEF may have LA myopathy out of proportion to left ventricular (LV) dysfunction; therefore, we sought to characterize HFpEF patients with disproportionate LA myopathy. In the prospective, multicenter, Prevalence of Microvascular Dysfunction in HFpEF study, we defined disproportionate LA myopathy based on degree of LA reservoir strain abnormality in relation to LV myopathy (LV global longitudinal strain [GLS]) by calculating the residuals from a linear regression of LA reservoir strain and LV GLS. We evaluated associations of disproportionate LA myopathy with hemodynamics and performed a plasma proteomic analysis to identify proteins associated with disproportionate LA myopathy; proteins were validated in an independent sample. Disproportionate LA myopathy correlated with better LV diastolic function but was associated with lower stroke volume reserve after passive leg raise independent of atrial fibrillation (AF). Additionally, disproportionate LA myopathy was associated with higher pulmonary artery systolic pressure, higher pulmonary vascular resistance, and lower coronary flow reserve. Of 248 proteins, we identified and validated 5 proteins (involved in cardiomyocyte stretch, extracellular matrix remodeling, and inflammation) that were associated with disproportionate LA myopathy independent of AF. In HFpEF, LA myopathy may exist out of proportion to LV myopathy. Disproportionate LA myopathy is a distinct HFpEF subtype associated with worse hemodynamics and a distinct proteomic signature, independent of AF

A Close Eye on the Eagle-Eyed Visual Acuity Hypothesis of Autism

Autism spectrum disorders (ASD) have been associated with sensory hypersensitivity. A recent study reported visual acuity (VA) in ASD in the region reported for birds of prey. The validity of the results was subsequently doubted. This study examined VA in 34 individuals with ASD, 16 with schizophrenia (SCH), and 26 typically developing (TYP). Participants with ASD did not show higher VA than those with SCH and TYP. There were no substantial correlations of VA with clinical severity in ASD or SCH. This study could not confirm the eagle-eyed acuity hypothesis of ASD, or find evidence for a connection of VA and clinical phenotypes. Research needs to further address the origins and circumstances associated with altered sensory or perceptual processing in ASD

Bengali translation and characterisation of four cognitive and trait measures for autism spectrum conditions in India

Background Autism is characterised by atypical social-communicative behaviour and restricted range of interests and repetitive behaviours. These features exist in a continuum in the general population. Behavioural measures validated across cultures and languages are required to quantify the dimensional traits of autism in these social and non-social domains. Bengali is the seventh most spoken language in the world. However, there is a serious dearth of data on standard measures of autism-related social and visual cognition in Bengali. Methods Bengali translations of two measures related to social-communicative functioning (the Children’s Reading the Mind in the Eyes Test (RMET) and a facial emotion recognition test with stimuli taken from the Karolinska Directed Emotional Faces database), one measure of visual perceptual disembedding (the Embedded Figures Test), and a questionnaire measure (the Children’s Empathy Quotient) were tested in 25 children with autism spectrum conditions (ASC) and 26 control children (mean age = 10.7 years) in Kolkata, India. Group differences were analysed by t test and multiple regression (after accounting for potential effects of gender, IQ, and age). Results Behavioural and trait measures were associated with group differences in the expected directions: ASC children scored lower on the Children’s Empathy Quotient and the RMET, as well as on facial emotion recognition, but were faster and more accurate on the Embedded Figures Test. Distributional properties of these measures within groups are similar to those reported in Western countries. Conclusions These results provide an empirical demonstration of cross-cultural generalisability and applicability of these standard behavioural and trait measures related to autism, in a major world language