Risk Factors for Relapse in Childhood Nephrotic Syndrome.

Minimal change nephrotic syndrome is the most common cause of the glomerular disease in children. Despite its high initial response to corticosteroids, relapses are common leading to increased morbidity. Therefore, appraisal of common triggers of relapse becomes an imperative for successful management of childhood nephrotic syndrome. The objective of the study was to identify the risk factors for frequent relapse in childhood nephrotic syndrome. This descriptive cross-sectional study was conducted in the department of Paediatrics, Rangpur Medical College Hospital, Bangladesh from January 2013 to December 2014. A total of 60 patients with relapsed idiopathic childhood nephrotic syndrome fulfilling the selection criteria were enrolled into the study. Serum total protein, serum albumin and urine culture were done. The following potential risk factors for relapse were analyzed using Chi-square test: age at onset of NS, sex, socioeconomic status, atopy, short duration of initial therapy with steriod, serum total protein, serum albumin level and infection. Among 60 patients, short duration of therapy with steriod (<8 weeks) for first attack was significantly higher among frequent relapse (FRNS) cases compared with infrequent relapse (IFRNS) group (63% vs. 27.27%). FRNS group had initial brief period of remission of <6 months, (p=0.04). Difference in mean serum albumin and that of serum total protein between FRNS and IFRNS cases was (1.0±0.66 vs. 2.66±1.6gm/dl) (p<0.0001) and (3.5±1.2 vs. 6.5±2.12gm/dl) (p<0 .0001) respectively. This study concluded that short initial therapy with corticosteroid, brief duration of initial remission; low serum total protein and decreased serum albumin were the risk factors for frequent relapses.

Comparison of WHO Clinical Criteria and Radiological Findings of Pneumonia in Children Aged 02-59 Months.

Despite recent advances, pneumonia contributes substantially to childhood mortality in low and middle-income countries. To reduce case fatality, World Health Organization (WHO) adopted a working formula to identify pneumonia clinically in resource constrained setting. Chest X-ray is the gold standard test to diagnose pneumonia but this tool is not readily available or affordable in primary health facility in developing countries even when it is indicated. Objective of the study was to compare WHO clinical criteria and radiological findings of pneumonia in children aged 02-59 months. This cross-sectional observational study was conducted at inpatient department of Paediatrics of Rangpur Medical College Hospital from July 2015 to June 2017. Total 112 patients aged 2 to 59 months fulfilling selection criteria were enrolled into this study. Data were collected and chest X-ray was done for each patient. Data were analyzed through SPSS software (version 16.0). Minimum level of significance was predetermined as p<0.05. Among 112 patients, mean age of chest radiograph positive cases of pneumonia was 7.64±7.08 months and that of negative cases 10.75±10.95 months. There was no statistically significant difference of age (p=0.083) between chest radiography positive and negative cases. Radiological findings were positive in 52(46.43%) cases and negative in 60(53.57%). Fever, cough and fast breathing were present in all patients with sensitivity 100%. Chest indrawing was significantly more (p=0.003) among 52(46.43%) cases who demonstrated positive radiological findings with sensitivity 63.46% (95% CI = 48.96% to 76.37%). There was no statistically significant difference of fever, cough and fast breathing between radiograph positive and negative cases. Chest indrawing was significantly more in radiograph positive cases. The results highlighted the importance of adoption of positive radiograph of WHO guideline to identify pneumonia.

Factors influencing local and distant recurrence following resection of periampullary cancer.

BACKGROUND: Recurrence of periampullary cancer after pancreatoduodenectomy is common. The aim of this study was to investigate patterns of recurrence, incidence, and factors associated with local and distant recurrences. METHODS: This retrospective, single-centre study included consecutive patients with periampullary cancer who underwent resection with curative intent from January 2012 to January 2018. Survival, patterns of recurrence, and factors associated with recurrences were analysed. RESULTS: Median overall survival (OS) and disease-free survival among 398 included patients was 58.4 and 49.5 months respectively. Twenty-three patients (5.8 per cent) developed isolated local recurrences (LR), 50 (12.6 per cent) developed LR along with distant metastasis (DM), and 103 (25.9 per cent) developed isolated DM. Median OS was 40.4 months for patients with isolated LR versus 23 months for those with DM (P < 0.001). Tumour subtype (distal common bile duct (CBD): odds ratio (OR) 6.18, 95 per cent c.i. 2.19 to 17.46) and node-positive status (OR 2.36, 1.26 to 4.43) were independently associated with higher rates of LR. The most common site for isolated LR was along the superior mesenteric artery (12 of 23 patients). Tumour subtype (distal CBD: OR 2.86, 1.09 to 7.52), nodal positivity (OR 2.46, 1.53 to 3.94), and presence of perineural invasion (OR 1.80, 1.02 to 3.18) were independently associated with DM. CONCLUSION: Isolated LR is associated with better survival than DM and occurs most commonly along the superior mesenteric artery.

Predicting the length of stay at admission for emergency general surgery patients a cohort study.

INTRODUCTION: Predicting length of stay (LOS) is beneficial to patients and the health service. When a prolonged LOS is predicted, it gives the opportunity for focused therapies and allocation of resources to reduce this period. In emergency general surgery (EGS) there has been limited investigation of variables that may be important predictors of LOS. This study examines social characteristics alongside measures of severity of acute illness and co-morbidities in an adult EGS population to establish their contribution to LOS. METHODS: Data were collected prospectively from patients at admission including medical variables, demographics, and therapeutic requirements. The length of hospital admission was measured, and multiple regression analysis was used to identify variables which predicted the LOS. RESULTS: Data were collected from 105 patients. The regression model gave an R2 of 0.34, p = 0.0006. Barthal index (measure of independence in activities of daily living) was a significant predictor of LOS [logworth 1.649, p0.02243]. Housing status and Level of social support both correlated in one-way analysis with LOS. CONCLUSION: There are non-surgical variables, measurable at admission which are of significant value in predicting LOS of EGS patients. This warrants further investigation through a larger study to better quantify the contributions of these variables, and establish potential early interventions to reduce the LOS.

A selective D2 dopamine receptor agonist alleviates depression through up-regulation of tyrosine hydroxylase and increased neurogenesis in hippocampus of the prenatally stressed rats.

Prenatal stress (PNS) has its negative impact on both the infant hippocampal neurogenesis and pregnancy outcomes in the neonates that serves as a risk factor for postnatal depression in adult offsprings. Therefore, main objectives of the present study were to evaluate the effect of maternal chronic unpredictable mild stress (CUMS) on behavioural changes, levels of oxidative stress, changes in selective developmental signaling genes and neurogenesis in the adult brain of Wistar rats and its reversal through a selective non-ergoline D2 type dopamine receptor (D2R) agonist Ropinirole (ROPI). Effects of ROPI treatment on CUMS induced adult rats offspring were measured by assessment of behavioural tests (sucrose preference test and forced swim test), biomarkers of oxidative stress, protein expression of tyrosine hydroxylase (TH), mRNA expression of SHH, GSK-3ß, ß-catenin, Notch, brain-derived neurotrophic factor (BDNF), Dopamine receptor 2 (Drd2) and bromodeoxyuridine (BrdU) cell proliferation assay. The oxidative stress, protein and mRNA expression were determined in the hippocampus and prefrontal cortex while the BrdU cell proliferation was observed in the hippocampus of rat brain. PNS induced changes resulted in depression validated by the depression-like behaviours, increased oxidative stress, decreased TH expression, altered expression of selective developmental genes, along with the reduced hippocampal neurogenesis and BDNF expression in the brain of adult offsprings. Chronic ROPI treatment reversed those effects and was equally effective like Imipramine (IMI) treatment. So, the present study suggested that ROPI can be used as an antidepressant drug for the treatment of depressive disorders.

Spin glass like transition and the exchange bias effect in Co3O4 nanoparticles anchored onto graphene sheets.

We have synthesized Co3O4 nanoparticles having 40 nm average size, which are anchored on reduced graphene oxide. X-ray diffraction, FESEM, TEM and Raman spectroscopy are performed for the characterization. The temperature dependence of field cooled (FC) and zero field cooled (ZFC) magnetization curves exhibits antiferromagnetic (AFM) transition around ∼30 K, as observed for bulk Co3O4. The exchange bias effect is observed below ∼30 K. A significant change in the exchange bias effect is noted around ∼8 K, which is close to a spin-glass-like transition. The spin-glass-like phase has been confirmed by the memory effects observed by different experimental protocols. The possible origin of exchange bias is discussed in the manuscript.

Umbrella Sampling and X-ray Crystallographic Analysis Unveil an Arg-Asp Gate Facilitating Inhibitor Binding Inside Phosphopantetheine Adenylyltransferase Allosteric Cleft.

Phosphopantetheine adenylyltransferase (PPAT) is a rate-limiting enzyme essential for biosynthesis of coenzyme A (CoA), which in turn is responsible to regulate the secretion of exotoxins via type III secretion system in Pseudomonas aeruginosa, causing severe health concerns ranging from nosocomial infections to respiratory failure. Acetyl coenzyme A (AcCoA) is a newly reported inhibitor of PPAT, believed to regulate the cellular levels of CoA and thereby the pathogenesis. Very little is known so far regarding the mechanistic details of AcCoA binding inside PPAT-binding cleft. Herein, we have used extensive umbrella sampling simulations to decipher mechanistic insight into the inhibitor accommodation inside the binding cavity. We found that R90 and D94 residues act like a gate near the binding cavity to accommodate and stabilize the incoming ligand. Mutational models concerning these residues also show considerable difference in AcCoA-binding thermodynamics. To substantiate our findings, we have solved the first crystal structure of apo-PPAT from P. aeruginosa, which also found to agree with the simulation results. Collectively, these results describe the mechanistic details of accommodation of inhibitor molecule inside PPAT-binding cavity and also offer valuable insight into regulating cellular levels of CoA/AcCoA and thus controlling the pathogenicity.

Personalized cumulative UV tracking on mobiles & wearables.

Maintaining a balanced Ultra Violet (UV) exposure level is vital for a healthy living as the excess of UV dose can lead to critical diseases such as skin cancer while the absence can cause vitamin D deficiency which has recently been linked to onset of cardiac abnormalities. Here, we propose a personalized cumulative UV dose (CUVD) estimation system for smartwatch and smartphone devices having the following novelty factors; (a) sensor orientation invariant measurement of UV exposure using a bootstrap resampling technique, (b) estimation of UV exposure using only light intensity (lux) sensor (c) optimal UV exposure dose estimation. Our proposed method will eliminate the need for a dedicated UV sensor thus widen the user base of the proposed solution, render it unobtrusive by eliminating the critical requirement of orienting the device in a direction facing the sun. The system is implemented on android mobile platform and validated on 1200 minutes of lux and UV index (UVI) data collected across several days covering morning to evening time frames. The result shows very impressive final UVI estimation accuracy. We believe our proposed solution will enable the future wearable and smartphone users to obtain a seamless personalized UV exposure dose across a day paving a way for simple yet very useful recommendations such as right skin protective measure for reducing risk factors of long term UV exposure related diseases like skin cancer and, cardiac abnormality.

Effect of Annealing on Optical, Electrical and Charge Trapping Properties of TiO2 NPs Arrays.

Glancing angle deposition technique has been carried out to synthesize TiO2 nanoparticles over SiO(x) thin film. The samples were annealed at different temperatures 550 °C and 950 °C. The average grain sizes and surface RMS roughness have been increased from 9 nm, 0.62 nm (as deposited); 21 nm, 2.47 nm (550 °C annealed) to 37 nm, 4.2 nm (950 °C annealed). Fivefold maximum increase in optical absorption has been recorded for the 950 °C annealed sample as compared to that of the as grown. The absorption and photoluminescence peaks show the red shift with an increase in annealing temperature and grain sizes. Transmission electron microscopy (TEM) has been used to investigate phases of nanoparticles. The junction capacitance of the Au/TiO2 NPs device was observed to decrease with an increase in frequency. A minimum change in junction capacitance of 1 pF was calculated for 950 °C annealed device for the variation of frequency from 500 Hz to 1 MHz. The results are used to simulate the capacitance as a function of frequency and voltage characteristic of TiO2 NPs based device in different temperature. Simulated results are exceptionally close to experimental results. The TiO2 NPs based device annealed at 950 °C possessed higher impedance and lower conductance among all three type of devices. The sample annealed at 950 °C showed the maximum capacitance (0.09 pF at 0 V) as well as charge (˜0.6 Coulomb at +8 V) retention compared to that of the 550 °C annealed and as deposited samples.

An {Fe60} tetrahedral cage: building nanoscopic molecular assemblies through cyanometallate and alkoxo linkers.

A nanoscopic {Fe60} coordination cage (approximately 3 nm) was prepared by the self assembly of a partially blocked tricyanidoferrate(iii) complex and tris(alkoxo)-based iron(iii) coordination motifs. This cage is a rare example of a mixed cyanido/alkoxo-bridged high nuclearity complex and it exemplifies the great potential of this new synthetic route to generate uncommon molecular architectures using cyanometallates as metalloligands versus alkoxo-based polynuclear entities.

Evaluation of synergistic effects of sulforaphene with photodynamic therapy in human cervical cancer cell line.

Sulforaphene from cruciferous vegetable has shown to modulate various signaling pathways of apoptosis. But it has not yet been studied extensively for the cervical cancer treatment. Previous studies show the promising role of photodynamic therapy for cervical cancer. Here, we confirm that sulforaphene can synergistically enhance the efficacy of photodynamic therapy. Human cervical cancer cells HeLa were treated with a very low dose of sulforaphene (2.0 µg/ml) and photodynamic therapy with radachlorin (0.5 µg/ml) at a fluence of 27 J/cm2 (30 milliwatts/cm2, λmax ∼ 670 ± 3 nm). The combination treatment showed a synergistic effect to induce apoptosis. The mitochondrial apoptotic pathway was activated via caspase 3 and caspase 9. On the other hand, caspase 12 and C/EBP homologous protein (CHOP) were expressed that indicated endoplasmic reticulum stress. This combination treatment also activated death receptor pathway via activation of caspase 8 and inhibited cell proliferation via down-regulation of EGFR. Thus, several apoptotic pathways were simultaneously activated in this combination treatment which results in a synergistic efficacy of sulforaphene with photodynamic therapy. Therefore, this study could be useful in the improvement of therapies for human cervical and other types of cancers.

TiO2 Nanowires/Poly(Methyl Methacrylate) Based Hybrid Photodetector: Improved Light Detection.

Hybrid photodetector with a maximum external quantum efficiency of ~3.08% in the UV region at 370 nm, was fabricated by spin-coated poly(methyl methacrylate) (PMMA) polymer onto glancing angle deposited (GLAD) vertically aligned TiO2 nanowire (NW) arrays. The TiO2 NWs/PMMA detector shows excellent rectification and constant 1.3 times photo-responsivity in the reverse bias condition from -1 V to -10 V. The photodiode possesses a low ideality factor of 5.1 as compared to bared TiO2 NWs device of 7.1. The hybrid device produces sharp turn-on of -0.8 s and turn-off transient of -0.9 s respectively.

Band Gap Tailoring of TiO2 Nanowires by Nitrogen Doping Under N2/Ar Plasma Environment.

Glancing angle deposited TiO2 nanowires (NWs) were doped with nitrogen (N) using plasma-enhanced chemical vapour deposition technique, under the treatment of N2/Ar plasma. A red shift (- 0.51 eV) in the main band transition and oxygen defect related transition (-2.1 eV) was observed for the N doped TiO2 nanowires. The interstitial nitrogen introduces mid-gap levels N (2P) above the O (2P) in the TiO2 forbidden gap. The photoluminescence measurement revealed a small red shift of -7 nm of anatase band gap from N doped TiO2 nanowires due to radiative recombination of carriers from conduction band to the N (2P) trap state. The low frequency Raman peaks at 304 cm(-1) (acoustical phonons with LA mode), 618 cm(-1) (optical phonons with LO modes) and the high frequency peak at 832 cm(-1) was observed from Ti-O-N due to the partial replacement of oxygen molecules by nitrogen into TiO2, during the doping process.

Improved Photo-Detection Using Zigzag TiO2 Nanostructures as an Active Medium.

Zigzag TiO2 nanostructures were fabricated using oblique angle deposition technique. The field emission gun-scanning electron microscope (FEG-SEM) image shows that the TiO2 zigzag nanostructures were ~500 nm in length. Averagely two times enhanced UV-Vis absorption was recorded for zigzag structure compared to perpendicular TiO2 nanowires. The main band transition was observed at ~3.4 eV. The zigzag TiO2 exhibited high turn on voltage (+11 V) than that of nanowire (+2 V) detector under dark which were reduced to +0.2 V and +1.0 V under white light illumination, respectively. A maximum ~6 fold photo-responsivity was observed for the zigzag TiO2 compared with nanowire device at + 1.0 V applied potential. The maximum photo-responsivity of 0.36 A/W at 370 nm was measured for the zigzag TiO2 detector. The TiO2 zigzag detector showed slow response with rise time of 10.2 s and fall time of 10.3 s respectively. The UV (370 nm) to visible (450 nm) wavelength rejection ratio of photo-responsivity was recorded ~4 times for the detector.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial.

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Rikkunshito induces gastric relaxation via the ß-adrenergic pathway in Suncus murinus.

BACKGROUND: Rikkunshito (RKT) is a gastroprotective herbal medicine. In this study, we investigated the role of RKT in the relaxation of the gastric body (fundus and corpus) and antrum. METHODS: We used Suncus murinus, a unique small model animal with similar gastrointestinal motility to humans and dogs. RKT was added at 0.1, 1.0, and 5.0 mg/mL to induce relaxation in vitro; the outcome measure was the intensity of relaxation. The number of spontaneous antral contractions in the absence or the presence of RKT was also counted. KEY RESULTS: Rikkunshito induced the relaxation of the gastric body and antrum and decreased the number of spontaneous antral contractions in a dose-dependent manner. The responses to RKT (1.0 mg/mL) were not affected by pretreatment with atropine, N-nitro-l-arginine methyl ester, ritanserin, or ondansetron. On the other hand, timolol almost completely reversed the relaxation induced by RKT (1.0 mg/mL) on the gastric body and antrum and the occurrence of the spontaneous antral contractions. Both butoxamine, a ß(2) -adrenoreceptor antagonist, and L 748337, a ß(3) -adrenoreceptor antagonist, but not CGP 20712, a ß(1) -adrenoreceptor antagonist, significantly reversed the RKT-induced (1.0 mg/mL) gastric relaxation. CONCLUSIONS & INFERENCES: These results indicate that RKT stimulates and modulates gastric relaxation through ß(2) - and ß(3) -adrenergic, but not ß(1) -adrenergic, pathways in S. murinus.

PerFlexMEA: a thin microporous microelectrode array for in vitro cardiac electrophysiological studies on hetero-cellular bilayers with controlled gap junction communication.

The new microelectrode array device presented is called PerFlexMEA and it enables controlled coupling between myocytes and nonmyocytes used in cardiovascular conduction studies. The device consists of an 8 µm thin parylene microporous membrane with a 4 × 5 microelectrode array patterned on one side. Myocytes and nonmyocytes can be plated on either side of the parylene membrane to create a tissue bilayer. The 3-3.5 µm diameter pores allow inter-layer dye and electrical coupling without transmembrane cell migration. Cell migration was found to vary with cell-type and micropore diameter. Pore density can be varied based on desired coupling ratio. The flexible parylene membrane is packaged between two rigid thermoplastic layers, such that the microelectrode array region is exposed, while the rest of the device remains insulated. The packaged PerFlexMEA fits in a 60 mm culture dish. Recording experiments are performed by simply plugging it into a commercially available multielectrode amplifier system. Recorded signals were processed and analysed using scripts generated in MATLAB. Our experimental results provide evidence of the reliability of this device, as conduction velocity was observed to decrease after inducing lateral hetero-cellular controlled coupling between myocytes and HeLa cells expressing connexin 43.

Utility and impact of early t(15;17) identification by Fluorescence In Situ Hybridization (FISH) in clinical decision making for patients in Acute Promyelocytic Leukemia (APL).

INTRODUCTION: Acute Promyelocytic Leukemia (APL) is a curable malignancy with studies showing above 90% survival. However, population-based studies looking at survival suggest that approximately 30% of patients with APL die during induction. Early demonstration of t(15;17) will lead to accurate decision making regarding treatment. The aim of this project was to validate earlier time frames for the Abbott Molecular Vysis LSI promyelocytic leukemia (PML)/ retinoic acid receptor alpha (RARA) fluorescence in situ hybridization (FISH) probe (ASR 6-16 h). METHODS: Twenty patients (15 APL cases and five non-APL cases) were selected for validating various hybridization times for the FISH probe. Expected normal signal pattern was two red and two green signals (2R2G), and the most common expected abnormal signal pattern was two fusion (yellow) signals, one red and one green (2F1R1G) and/or one fusion, one red and one green (1F1R1G). RESULTS: The specificity of the probe ranged from 84% at 2 h, 86% at 4 h, 84% at 6 h, and 87% for overnight hybridization. The sensitivity increased from 79% at 2 h, 80% at 4 h, 81% at 6 h to 87% for overnight hybridization. CONCLUSION: Based on the validation studies, we recommend reading of FISH results at the 4-h incubation mark for a preliminary diagnosis and confirmation with overnight hybridization.