Anthropometric cut points for identification of cardiometabolic risk factors in an urban Asian Indian population

The aim of this study was to determine the anthropometric cut points for risk of cardiometabolic risk factors in an urban Asian Indian population. The Chennai Urban Rural Epidemiology Study representatively sampled 26001 individuals aged 20 years or older and detailed measures were obtained in every 10th subject: 90.4% (2350/2600). An oral glucose tolerance test was performed in all individuals except self-reported diabetic subjects. Anthropometric measurements such as body mass index (BMI) and waist circumference (WC) were obtained and serum lipid estimations were done in all subjects. Sensitivity, specificity, and distance on receiver operating characteristic curve were used to determine the optimal cut points for BMI and WC with cardiometabolic risk factors. Maximum sensitivity and specificity of BMI for all cardiometabolic risk factors such as diabetes mellitus, prediabetes, hypertension, hypertriglyceridemia, hypercholesterolemia, and low high-density lipoprotein cholesterol ranged from 22.7 to 23.2 kg/m(2) for men and 22.7 to 23.8 kg/m(2) for women, and that of WC ranged from 86 to 88.2 cm for men and 81 to 83.8 cm for women. The optimal BMI cut point for identifying any 2 cardiometabolic risk factors was 23 kg/m(2) in both sexes, whereas that of WC was 87 cm for men and 82 cm for women. The study validates the World Health Organization Asia Pacific guidelines of BMI of 23 kg/m(2) for the designation of overweight; WC of 87 cm for men and 82 cm for women appear to be appropriate cut points to identify cardiometabolic risk factors including prediabetes in urban Asian Indians.     

Spinal analgesia and auditory functions: a comparison of two sizes of Quincke needle

AIM: Spinal anaesthesia may produce complications ranging from minor problems such as pain on injection, backache and urinary retention to more serious consequences such as post-dural puncture headache (PDPH), neurological complications like meningitis, cranial and peripheral nerve palsies and even cardiac arrest. Impaired auditory function is a relatively lesser-recognized complication of spinal analgesia. The objective of this study was to investigate the effects of spinal analgesia on vestibular dysfunction, using different sizes of the same type of spinal needle. METHODS: The study included 30 ASA I patients who had received spinal analgesia for lower abdominal surgery. Pure tone audiometry was performed before surgery and on postoperative day 2. In addition, any patient with hearing impairment of >15 dB was scheduled to undergo electrocochleography. Hearing levels were measured from 250 Hz to 8 kHz. In group 1 (n=15), a 26gauge Quincke needle was used. In group 2 (n=15), a 23-gauge Quincke needle was used. RESULTS: Comparison of hearing thresholds showed a significant reduction in the hearing level (P<0.05) in 2 patients in group 2 but none in group 1. CONCLUSION: The use of a 23-gauge Quincke needle is associated with a greater reduction in the mean hearing level compared to a 26-gauge needle of the same type.     

Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in Gerbils

Despite of the huge socio-economic burden, stroke still represents an unmet therapeutic need. Researchers failed to reproduce preclinical efficacy in subsequent clinical development. To bridge this translation failure, the Stroke Therapy Academic Industry Round Table (STAIR) has suggested a rigorous, robust, and detailed preclinical evaluation in at least 2 species and multiple cerebral ischemia models to avoid the clinical failure. Considering these recommendations, in the present study, we have investigated the effects of pioglitazone in global model cerebral ischemic-reperfusion (IR) injury in gerbils. Global cerebral IR injury, produced by bilateral carotid artery occlusion for 5 min, was characterized by neurological deficits, hyperlocomotion, and neurodegeneration in the hippocampal CA1 region. Global ischemia was also associated with oxidative stress and DNA fragmentation as evident from increased malondialdehyde (MDA) levels and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells. Global cerebral IR injury associated neurological damage was significantly attenuated by pioglitazone pretreatment as evident from reduction in neurological symptoms, hyperlocomotion, and CA1 hippocampal neuronal damage in IR-challenged gerbils. Pioglitazone pretreatment also attenuated the oxidative stress and DNA fragmentation after cerebral IR injury. Pioglitazone post-treatment has also significantly reduced the CA1 hippocampal neuronal damage and DNA fragmentation after cerebral IR injury in IR-challenged gerbils. This study demonstrates the neuroprotective activity of pioglitazone in global cerebral IR injury and its neuroprotective effects may be attributed to reduction in oxidative stress and DNA fragmentation.     

Giant ruptured sinus of Valsalva aneurysm: diagnosis on echocardiography

A giant ruptured sinus of Valsalva aneurysm was diagnosed ontransthoracic and subsequent transesophageal echocardiography,in a 45-year-old man who presented with gradual onset shortnessof breath. Although the initial presentation was insidious,he later rapidly deteriorated. We discuss the unusual clinicalcourse in a patient with such a large aneurysm and discuss thelikely reasons.     

Novel variants in UBE2B gene and idiopathic male infertility

The UBE2B gene encodes ubiquitin-conjugating enzyme, which is involved in DNA repair. Ube2b knockout mice were found to be infertile because of structural abnormality of sperm. However, there is no genetic study on the role of the UBE2B gene in human fertility; therefore, the present investigation was designed to study genetic variations in the UBE2B gene and its role in human male infertility. Sequence analyses of the UBE2B gene in 530 infertile (350 azoospermic, 105 oligoasthenoteratozoospermic, and 75 oligoasthenozoospermic) and 300 fertile control men revealed the presence of 5 substitution single-nucleotide polymorphisms (SNPs) in 221 individuals (199 infertile [37.5%] and 22 fertile [7.3%] men). Of these, 2 (g.5197:T>G; g.9157:A>G) of the 5 substitutions were novel and observed only in infertile men. Distribution of haplotypes TA, TG, GA, and GG are not uniform between the patient and the control group of this study. Interestingly, our study suggests that the haplotype TG conferred significantly increased risk for male infertility (odds ratio = 5.07, 95% CI = 1.29-23.29, p = .007). In silico analysis of SNPs that were specific to infertile men predicted that these SNPs lead to defective splicing by destroying or creating the potential binding site of splicing factors or causing alteration in predicted regulatory sequences. In the light of the above, our study suggests that the UBE2B gene is associated with male infertility in Indian men, hence, providing evidence for additional genetic factors for male infertility.     

Synthesis and characterization of nonsteroidal glucocorticoid receptor modulators for multiple myeloma

Structure-activity relationship studies centered around 3'-substituted (Z)-5-(2'-(thienylmethylidene))1,2-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5H-chromeno[3,4-f]quinolines are described. A series of highly potent and efficacious selective glucocorticoid receptor modulators were identified with in vitro activity comparable to dexamethasone. In vivo evaluation of these compounds utilizing a 28 day mouse tumor xenograft model demonstrated efficacy equal to dexamethasone in the reduction of tumor volume.     

Evaluation of the effect of SMA-pirarubicin micelles on colorectal cancer liver metastases and of hyperbaric oxygen in CBA mice

Tetrahydropyranyladriamycin (THP or pirarubicin) destroys tumors via several mechanisms; one of which involves the production of ROS that requires molecular oxygen for its generation. SMA forms stable self-assembled associated micelles with pirarubicin (SMA-pirarubicin), and confers macromolecular characteristics to pirarubicin. This micellar macromolecular drug is selectively delivered to solid tumors via the EPR effect and its preferential tumor accumulation suppresses the systemic toxicity whilst its prolonged high concentration at the site of tumor enhances its efficacy much higher compared to free pirarubicin. Administration of SMA-pirarubicin micelle under HBO can further enhance the delivery of molecular oxygen that facilitates tumor selective generation of ROS, thus augmenting its antitumor potency. In this study, we evaluated the efficacy of SMA-pirarubicin micelles either as single drug or in combination with HBO in a mouse metastatic colorectal cancer model. At or below the maximum tolerated dose, SMA-pirarubicin remarkably reduced metastatic tumor nodules and it was far more effective than free pirarubicin. The data also suggests a potential benefit of combined therapy of HBO with micellar anthracyclins.