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Byline: S. Kandasami, R. Rao, M. Arul, M. Ranganath, T. Prasad Percutaneous nephrolithotripsy is the treatment of choice for large renal calculi. Total stone clearance as the treatment goal remains [...]

Byline: R. Rao, M. Ranganath, T. Prasad Stone management in horseshoe kidneys is challenging: percutaneous nephrolithotripsy is a safe and effective procedure in the treatment of large stones within horseshoe [...]

We address a problem with the Bergman-Cobelli Minimal Model, which has been used for 40 years to estimate SI during an intravenous glucose tolerance test (IVGTT). During the IVGTT blood glucose and insulin concentrations are measured in response to an acute intravenous glucose load. Insulin secretion is often assessed by the area under the insulin curve during the first few minutes (Acute Insulin Response, AIR). The issue addressed here is that we have found in simulated IVGTTs, representing certain contexts, Minimal Model estimates of SI are inversely related to AIR, resulting in artifactually lower SI. This may apply to Minimal Model studies reporting lower SI in Blacks than in Whites, a putative explanation for increased risk of T2D in Blacks. The hyperinsulinemic euglycemic clamp (HIEC), the reference method for assessing insulin sensitivity, by contrast generally does not show differences in insulin sensitivity between these groups. The reason for this difficulty is that glucose rises rapidly at the start of the IVGTT and reaches levels independent of SI, whereas insulin during this time is determined by AIR. The minimal model in effect interprets this combination as low insulin sensitivity even when actual insulin sensitivity is unchanged. This happens in particular when high AIR results from increased number of readily releasable insulin granules, which may occur in Blacks. We conclude that caution should be taken when comparing estimates of SI between Blacks and Whites.

Decreased cardiac myosin-binding protein C (cMyBPC) expression due to inheritable mutations is thought to contribute to the hypertrophic cardiomyopathy (HCM) phenotype, suggesting that increasing cMyBPC content is of therapeutic benefit. In vitro assays show that cMyBPC N-terminal domains (NTDs) contain structural elements necessary and sufficient to modulate actomyosin interactions, but it is unknown if they can regulate in vivo myocardial function. To test whether NTDs can recapitulate the effects of full-length (FL) cMyBPC in rescuing cardiac function in a cMyBPC-null mouse model of HCM, we assessed the efficacy of AAV9 gene transfer of a cMyBPC NTD that contained domains C0C2 and compared its therapeutic potential with AAV9-FL gene replacement. AAV9 vectors were administered systemically at neonatal day 1, when early-onset disease phenotypes begin to manifest. A comprehensive analysis of in vivo and in vitro function was performed following cMyBPC gene transfer. Our results show that a systemic injection of AAV9-C0C2 significantly improved cardiac function (e.g., 52.24 ± 1.69 ejection fraction in the C0C2-treated group compared with 40.07 ± 1.97 in the control cMyBPC–/– group, P < 0.05) and reduced the histopathologic signs of cardiomyopathy. Furthermore, C0C2 significantly slowed and normalized the accelerated cross-bridge kinetics found in cMyBPC–/– control myocardium, as evidenced by a 32.41% decrease in the rate of cross-bridge detachment (krel). Results indicate that C0C2 can rescue biomechanical defects of cMyBPC deficiency and that the NTD may be a target region for therapeutic myofilament kinetic manipulation.

Background Recent studies suggest that mavacamten (Myk461), a small myosin‐binding molecule, decreases hypercontractility in myocardium expressing hypertrophic cardiomyopathy‐causing missense mutations in myosin heavy chain. However, the predominant feature of most mutations in cardiac myosin binding protein‐C (cMyBPC) that cause hypertrophic cardiomyopathy is reduced total cMyBPC expression, and the impact of Myk461 on cMyBPC‐deficient myocardium is currently unknown. Methods and Results We measured the impact of Myk461 on steady‐state and dynamic cross‐bridge (XB) behavior in detergent‐skinned mouse wild‐type myocardium and myocardium lacking cMyBPC (knockout (KO)). KO myocardium exhibited hypercontractile XB behavior as indicated by significant accelerations in rates of XB detachment (krel) and recruitment (kdf) at submaximal Ca2+ activations. Incubation of KO and wild‐type myocardium with Myk461 resulted in a dose‐dependent force depression, and this impact was more pronounced at low Ca2+ activations. Interestingly, Myk461‐induced force depressions were less pronounced in KO myocardium, especially at low Ca2+ activations, which may be because of increased acto‐myosin XB formation and potential disruption of super‐relaxed XBs in KO myocardium. Additionally, Myk461 slowed krel in KO myocardium but not in wild‐type myocardium, indicating increased XB “on” time. Furthermore, the greater degree of Myk461‐induced slowing in kdf and reduction in XB recruitment magnitude in KO myocardium normalized the XB behavior back to wild‐type levels. Conclusions This is the first study to demonstrate that Myk461‐induced force depressions are modulated by cMyBPC expression levels in the sarcomere, and emphasizes that clinical use of Myk461 may need to be optimized based on the molecular trigger that underlies the hypertrophic cardiomyopathy phenotype.

Abstract The known interactions between the somatotropic and hypothalamic‐pituitary‐gonadal (HPG) axes have not been well delineated in older individuals. Aging‐associated decline in insulin like growth factor‐1 (IGF‐1) levels has been proposed to play a role in reproductive senescence in animals. However, the effects of GH on LH secretion are unknown in older individuals. Our objective was to determine whether GH modulates LH secretion or levels of sex steroids (SS) in healthy older (ages 65–88 years) men (n = 24) and women (n = 24) with low‐normal plasma IGF‐1 levels. In a double‐masked, placebo‐controlled (n = 24), randomized study, we evaluated the effects of GH (n = 24, 20 μg/kg sc 3×/week) for 26 weeks on nocturnal LH secretory dynamics [(8 pm to 8 am, Q20) min sampling and analyzed by multiparameter deconvolution algorithm]. Indices of LH secretion [frequency, mass per burst, pulsatile production rate, and approximate entropy (ApEn)] and fasting serum IGF‐1, SHBG, and SS (TT, fT, or E2) were measured. At baseline, all indices of LH secretion (frequency, mass per burst, pulsatile production rate) were inversely (P

Circuit model of photovoltaic (PV) module is presented in this paper that can be used as a common platform by material scientists and power electronic circuit designers to develop better PV power plant. Detailed modeling procedure for the circuit model with numerical dimensions is presented using power system blockset of MATLAB/Simulink. The developed model is integrated with DC-DC boost converter with closed-loop control of maximum power point tracking (MPPT) algorithm. Simulation results are validated with the experimental setup.

This research paper depicts the process of used liquid nitrogen at the interface of TiN coated carbide cutting tool insert (rake face) and AISI D3 workpiece. Design of experiments (DoE) was planned according to Taguchi L9 (OA) orthogonal array. The experimental results during machining such as cutting force, machining time and temperature were optimized by Taguchi S/N ratio and analysed by ANOVA. The contribution of machining parameters of (i) speed, (ii) feed and (iii) depth of cut for each response were evaluated. Feed had the highest effect on the percentage of contribution of 57.21% and 52.21% for cutting force and machining time, respectively. Speed had the highest effect on the contribution as 79.57% for the temperature at the interface of insert and workpiece. The predicted values at the optimum level of machining parameters for cutting force, machining time and temperature were 44.49 N, 37.09 sec. and 24.99°C, respectively. Regression models were made. The R-Sq values were 96.59, 89.34 and 96.09% for cutting force, machining time and temperature, respectively. The ratio of an average thickness of generated chip and feed was considered as the chip compression ratio. It was observed that the generated chips during cryogenic turning were thin, discontinuous, long snarled and most of the material had side flow on either side. [ABSTRACT FROM AUTHOR]