Screening of patients with tuberculosis for diabetes mellitus in China

Objective There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and this study aimed to assess feasibility and results of screening patients with TB for DM within the routine healthcare setting of six health facilities. Method Agreement on how to screen, monitor and record was reached in May 2011 at a stakeholders’ meeting, and training was carried out for staff in the six facilities in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. Results There were 8886 registered patients with TB. They were first asked whether they had DM. If the answer was no, they were screened with a random blood glucose (RBG) followed by fasting blood glucose (FBG) in those with RBG ≥ 6.1 mm (one facility) or with an initial FBG (five facilities). Those with FBG ≥ 7.0 mm were referred to DM clinics for diagnostic confirmation with a second FBG. Altogether, 1090 (12.4%) patients with DM were identified, of whom 863 (9.7%) had a known diagnosis of DM. Of 8023 patients who needed screening for DM, 7947 (99%) were screened. This resulted in a new diagnosis of DM in 227 patients (2.9% of screened patients), and of these, 226 were enrolled to DM care. In addition, 575 (7.8%) persons had impaired fasting glucose (FBG 6.1 to <7.0 mm ). Prevalence of DM was significantly higher in patients in health facilities serving urban populations (14.0%) than rural populations (10.6%) and higher in hospital patients (13.5%) than those attending TB clinics (8.5%). Conclusion This pilot project shows that it is feasible to screen patients with TB for DM in the routine setting, resulting in a high yield of patients with known and newly diagnosed disease. Free blood tests for glucose measurement and integration of TB and DM services may improve the diagnosis and management of dually affected patients.     

Prediction of primary vs secondary hypertension in children

Despite current guidelines, variability exists in the workup of hypertensive children due to physician preferences. The study evaluates primary vs secondary hypertension diagnosis from investigations routinely performed in hypertensive children. This retrospective study included children 5 to 19 years with primary and secondary hypertension. The proportions of abnormal laboratory and imaging tests were compared between primary and secondary hypertension groups. Risk factors for primary vs secondary hypertension were evaluated by logistic regression and likelihood function analysis. Patients with secondary hypertension were younger (5-12 years) and had a higher proportion of abnormal creatinine, renal ultrasound, and echocardiogram findings. There was no significant difference in abnormal results of thyroid function, urine catecholamines, plasma renin, and aldosterone. Abnormal renal ultrasound findings and age were predictors of secondary hypertension by regression and likelihood function analysis. Children aged 5 to 12 years with abnormal renal ultrasound findings and high diastolic blood pressures are at higher risk for secondary hypertension that requires detailed evaluation.     

A mild and metal-free synthesis of 2- and 1-alkyl/aryl/dialkyl-aminoquinolines and isoquinolines

A simple synthetic strategy has been developed for the synthesis of 2- and 1-alkyl/aryl/dialkylaminoquinolines and isoquinolines from the easily available quinoline and isoquinoline-N-oxides, different amines, triflic anhydride as activating agent and acetonitrile as solvent in a one-pot reaction under metal-free conditions at 0 °C to room temperature.

A synthetic strategy has been developed for synthesis of 2 and 1-aminoquinolines and isoquinolines from quinoline and isoquinoline-N-oxides, amines and triflic anhydride in acetonitrile at 0 °C to room temperature.     

Coupling of Proton Binding in Extracellular Domain to Channel Gating in Acid-Sensing Ion Channel

Protonation of several amino acid residues in the extracellular domain (ECD) of acid-sensing ion channel (ASIC) causes conformational changes that lead to opening of the channel. It is not clear how conformational changes in ECD are coupled to channel gating. Here, we show that the loop connecting β9 and α4 at the base of the thumb region of ECD interacts with post-TM1 to stabilize the channel in the closed state. Flexibility of these two regions is important for optimum gating of the channel. In ASIC1a, when Y71 (post-TM1) and W287 (β9–α4 loop) were mutated to cysteine, they formed disulfide bond in the closed state. Breaking of the disulfide bond by reducing agent dithiothreitol (DTT) or tris(2-carboxyethyl)phosphine (TCEP) potentiated the current significantly. Engineered cysteine G288C reacted with sulfhydryl-specific methanethiosulfonate ethyltrimethylammonium (MTSET) in the open state but not in closed/steady desensitized state, suggesting gating-associated conformational movement of this loop. We also identified a salt bridge between highly conserved R64 at TM1 and D432 at TM2 that is important for optimum gating. Based on our results and other published work, we propose that proton binding in ECD is followed by the displacement of the β9–α4 loop of the thumb, leading to the rotation of TM1. Conformational movement propagates to TM2 and the channel gate opens by the concomitant movement of TM2 and breaking of the salt bridge between R64 and D432.     

Alterations in GABA(A) receptor mediated inhibition in adjacent dorsal midline thalamic nuclei in a rat model of chronic limbic epilepsy

There is evidence that the dorsal midline thalamus is involved in the seizures of limbic epilepsy. However, little is known about the inhibitory synaptic function in this region. In the present study, inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors were recorded from the mediodorsal (MD) and paraventricular (PV) nuclei from control and epileptic animals. In the MD, the spontaneous (s)IPSCs for epileptic animals had a lower frequency, prolonged rise time, prolonged decay, but unaltered net charge transfer compared with controls. The miniature (m)IPSC parameters were unaltered in the epileptic animals. In contrast, in the PV, both sIPSCs and mIPSCs in the epileptic animals were more frequent with larger amplitudes and there was an increase in the net charge transfer compared with controls. The rise times of the sIPSCs of the PV neurons were significantly prolonged, whereas the weighted decay time of the mIPSC was significantly shortened in epileptic animals. These findings suggest that the changes associated with inhibitory synaptic transmission in limbic epilepsy are not uniform across regions in the thalamus that are part of the seizure circuit.     

Evaluating thin compression paddles for mammographically compatible ultrasound

We are developing a combined digital mammography/3D ultrasound system to improve detection and/or characterization of breast lesions. Ultrasound scanning through a mammographic paddle could significantly reduce signal level, degrade beam focusing and create reverberations. Thus, appropriate paddle choice is essential for accurate sonographic lesion detection and assessment with this system. In this study, we characterized ultrasound image quality through paddles of varying materials (lexan, polyurethane, TPX, mylar) and thicknesses (0.25 to 2.5 mm). Analytical experiments focused on lexan and TPX, which preliminary results demonstrated were most competitive. Spatial and contrast resolution, side-lobe and range lobe levels, contrast and signal strength were compared with no-paddle images. When the beamforming of the system was corrected to account for imaging through the paddle, the TPX 2.5 mm paddle performed the best. Test objects imaged through this paddle demonstrated < or = 15% reduction in spatial resolution, < or = 7.5 dB signal loss, < or = 3 dB contrast loss and range lobe levels > or = 35 dB below signal maximum over 4 cm. TPX paddles <2.5 mm could also be used with this system, depending on imaging goals. In 10 human subjects with cysts, small CNR losses were observed but were determined to be statistically insignificant. Radiologists concluded that 75% of cysts in through-paddle scans were at least as detectable as in their corresponding direct-contact scans.     

A review of meibography for a refractive surgeon

Refractive surgery has evolved from being a therapeutic correction of high refractive errors to a cosmetic correction. The expectations associated with such a surgery are enormous and one has to anticipate all possible complications and side-effects that come with the procedure and prepare accordingly. The most common amongst these is post-refractive surgery dry eye of which Meibomian gland dysfunction is a commonly associated cause. We present an understanding of various diagnostic imaging modalities that can be used for evaluating meibomian glands which can also serve as a visual aid for patient understanding. We also describe various common conditions which can silently cause changes in the gland architecture and function which are to be considered and evaluated for.