One-stage repair of cardiac and arch anomalies without circumlatory arrest

Indian Journal of Thoracic and Cardiovascular Surgery -     

Evaluation of Evidence for Pathogenicity Demonstrates That BLK,KLF11, and PAX4 Should Not Be Included in Diagnostic Testing for MODY

Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of monogenic diabetes, reported to be caused by variants in 16 genes. Concern has been raised about whether variants in BLK (MODY11), KLF11 (MODY7), and PAX4 (MODY9) cause MODY. We examined variant-level genetic evidence (cosegregation with diabetes and frequency in population) for published putative pathogenic variants in these genes and used burden testing to test gene-level evidence in a MODY cohort (n = 1,227) compared with a control population (UK Biobank [n = 185,898]). For comparison we analyzed well-established causes of MODY, HNF1A, and HNF4A. The published variants in BLK, KLF11, and PAX4 showed poor cosegregation with diabetes (combined logarithm of the odds [LOD] scores ≤1.2), compared with HNF1A and HNF4A (LOD scores >9), and are all too common to cause MODY (minor allele frequency >4.95 × 10⁻⁵). Ultra-rare missense and protein-truncating variants (PTV) were not enriched in a MODY cohort compared with the UK Biobank population (PTV P > 0.05, missense P > 0.1 for all three genes) while HNF1A and HNF4A were enriched (P < 10⁻⁶). Findings of sensitivity analyses with different population cohorts supported our results. Variant and gene-level genetic evidence does not support BLK, KLF11, or PAX4 as a cause of MODY. They should not be included in MODY diagnostic genetic testing.     

Carcinoma of the ampulla of Vater

Experience in treating tumours of the ampulla of Vater in the North West region of the UK is reviewed. The results of local resection, radical resection and palliative bypass in 61 cases have been compared. Local resection in this series offers a better survival than radical procedures at one, two, three, and five years. The operative mortality for radical procedures was 30 per cent. There were no operative deaths in those patients having a local resection. No patient having palliative bypass surgery survived more than 18 months.     

Determining rate of subjective time according to subject sex,weight, and locus of control orientation

The purpose of the study was to investigate what relationship if any existed among such contingencies as the ability to determine rate of subjective time (RST), the problem of obesity, and the predisposition toward a specific locus of control. A 2 × 2 × 2 ANOVA factorial design was used with 95 subjects who were assigned to 1 of 8 cells according to their weight, sex, and score on the Rotter Internal-External Locus of Control Scale. A significant finding was that there was a main effect for subject weight (p < .008), i.e., obese subjects had significantly faster RSJ's than their nonobese counterparts. RST was independent of locus of control and subject sex. Results of the study support the role of physiological factors in the etiology of obesity and reveal what may be a common mechanism in the etiology of both obesity and time perception based on hypothalamic function. Implications for future research on the treatment of obesity are discussed.     

Systemic protection by antioxidants against UVL-induced erythema

An antioxidant supplemented diet provided marked systemic protection against ultraviolet light mediated erythema in hairless mice. Among the individual constituents of the diet, butylated hydroxytoluene was most effective whereas glutathione and vitamins C and E afforded negligible protection. The mixture of antioxidants, and butylated hydroxytoluene individually, demonstrated diminished, but significant, protection when applied topically. The safety of this systemic photoprotectant and its clinical relevance at present is unknown.     

Phenotypic stability of the cell wall of Streptococcus mutans Ingbritt grown under various conditions.

Quantitative analyses of cell walls from Streptococcus mutans Ingbritt grown under carbohydrate limitation in the chemostat showed that growth conditions had no statistically significant effect on the composition of polysaccharide, peptidoglycan, or the proportion of polysaccharide in the cell wall. Lysis of cell wall preparations with a muramidase supported this conclusion and further indicated that there was little difference in their overall structure. In contrast, there was a consistent difference between the rates of lysis by this enzyme of organisms grown in 0.2% glucose and 0.5% glucose. Extremes of pH or dilution rate essentially did not influence the immunogenicity of type c antigen in whole organisms irrespective of whether the carbohydrate source was glucose or sucrose. However, differences were found in the immunogenicity of lipoteichoic acid under similar circumstances. The results indicated there was an inherent phenotypic stability in the cell walls of S. mutans Ingbritt despite changes in pH, generation time, and carbohydrate source, and that any changes that did occur were probably due to associated cell-surface components.     

Single prolonged stress decreases glutamate,glutamine, and creatine concentrations in the rat medial prefrontal cortex

Application of single prolonged stress (SPS) in rats induces changes in neuroendocrine function and arousal that are characteristic of post traumatic stress disorder (PTSD). PTSD, in humans, is associated with decreased neural activity in the prefrontal cortex, increased neural activity in the amygdala complex, and reduced neuronal integrity in the hippocampus. However, the extent to which SPS models these aspects of PTSD has not been established. In order to address this, we used high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS ¹H MRS) ex vivo to assay levels of neurochemicals critical for energy metabolism (creatine and lactate), excitatory (glutamate and glutamine) and inhibitory (gamma amino butyric acid (GABA)) neurotransmission, and neuronal integrity (N-acetylaspartate (NAA)) in the medial prefrontal cortex (mPFC), amygdala complex, and hippocampus of SPS and control rats. Glutamate, glutamine, and creatine levels were decreased in the mPFC of SPS rats when compared to controls, which suggests decreased excitatory tone in this region. SPS did not alter the neurochemical profiles of either the hippocampus or amygdala. These data suggest that SPS selectively attenuates excitatory tone, without a disruption of neuronal integrity, in the mPFC.     

Effect of nucleus basalis magnocellularis cholinergic lesions on fear-like and anxiety-like behavior

Previous research has suggested that cholinergic neurons in the nucleus basalis magnocellularis and substantia innominata (NBM/SI) may be important in mediating aversive states. The authors investigated the effect of NBM/SI cholinergic lesions, induced with 192 IgG saporin, on behavioral measures of aversive states in rats. Behavior in the elevated plus maze and behavioral suppression induced by 2 fear-conditioned stimuli, a tone and a light, were evaluated. Lesions had no effect on any measures in the elevated plus maze but attenuated operant suppression induced by the light and attenuated freezing induced by the tone, though this last effect was not statistically significant. The results of the study suggest that NBM/SI cholinergic neurons may be important in mediating selective aspects of aversive states.     

Conscious sedation and analgesia for oocyte retrieval during IVF procedures: a Cochrane review

BACKGROUND: Various methods of sedation and analgesia have been used for pain relief during oocyte recovery during IVF. OBJECTIVE: To compare conscious sedation and analgesia with alternative methods for pain relief and pregnancy outcomes. METHODS: We searched the Specialised Register of the Menstrual Disorders and Subfertility Group, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the National Research Register and Current Controlled Trials up to February 2004. RESULTS: Twelve trials were included. Owing to considerable heterogeneity, regarding types and dosages of sedation or analgesia used, and tools used to assess pain, a meta-analysis was attempted only in trials where appropriate data were available. Clinical pregnancy rates per woman in individual trials were comparable. Data on pain showed conflicting results. CONCLUSION: No single method or delivery system appeared superior for pregnancy rates and pain relief. Future studies need to be consistent in the choice of tools used to measure pain and the timing of such evaluations.