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BACKGROUND: TB control remains a serious public health problem, compounded by poor treatment adherence, which increases the likelihood of onward transmission. We evaluated the effectiveness of medication event reminder monitoring (MERM) upon treatment adherence in a high TB burden setting.METHODS: We conducted an open-label parallel group randomised controlled trial among pulmonary TB adults. Participants were provided with a MERM device to store their medications. In the intervention arm, the devices were set to provide daily medication intake reminders. Primary outcome was the proportion of patient-months in which at least 6/30 doses were missed. Secondary outcomes included 1) the proportion of patient-months in which at least 14/30 doses were missed, and 2) the proportion of doses missed.RESULTS: Of 2,142 patients screened, 798 (37.3%) met the inclusion criteria and 250 participants were enrolled. The mean ratio (MR) for poor adherence between the intervention and control groups was 0.72 (95% CI 0.55–0.86). The intervention was also associated with a reduction in the proportion of patients missing at least 14/30 doses (MR 0.61, 95% CI 0.54–0.68) and the percentage of total doses missed (MR 0.75, 95% CI 0.68–0.80).CONCLUSION: MERM is effective in improving TB treatment adherence in a resource-limited environment.

This paper presents the results of the research on the influence of plasma nitriding technology parameters on the working surface deformation of hypoid gears. Blue light technology with non-contact measuring devices is used to determine the working surface deformation of hypoid gears after plasma nitriding. The study has determined a regression equation showing the influence of plasma nitriding technology parameters on the deformation of the working surface of the hypoid gear. The minimum deformation optimization value at the planning area is 0.0071746 at permeation temperature TL=4.89oC, permeation time h=510h, and gas flow 1 G1=6.02L/h.

The Multi-Criteria Decision-Making (MCDM) process of milling SNCM439 steel is presented in this study. In this experimental study, 3 cutting tool parameters, namely the number of pieces, cutting piece material, and tip radius were considered and 3 cutting mode parameters, i.e. cutting speed, feed rate, and depth of cut changed in each experiment. SR and MRR are selected as the output parameters of the milling process. The PARIS method was used for MCDM, in which, the weights of SR and MRR were determined by 3 methods, namely AW, EW, and MW. Twenty-seven sets of ranking results for 27 alternatives (experiments) are presented. The GINI index was used to evaluate the stability of ranking alternatives. The results have determined the value of 6 input parameters to ensure the minimum SR and the maximum MRR simultaneously.

IntroductionFetal alcohol spectrum disorders (FASD) are the most common cause of non-heritable, preventable mental disability, occurring in almost 5% of births in the United States. FASD lead to physical, behavioral, and cognitive impairments, including deficits related to the cerebellum. There is no known cure for FASD and their mechanisms remain poorly understood. To better understand these mechanisms, we examined the cerebellum on a cellular level by studying microglia, the principal immune cells of the central nervous system, and Purkinje cells, the sole output of the cerebellum. Both cell types have been shown to be affected in models of FASD, with increased cell death, immune activation of microglia, and altered firing in Purkinje cells. While ethanol administered in adulthood can acutely depress the dynamics of the microglial process arbor, it is unknown how developmental ethanol exposure impacts microglia dynamics and their interactions with Purkinje cells in the long term.MethodsTo address this question, we used a mouse model of human 3rd trimester exposure, whereby L7cre/Ai9+/−/Cx3cr1G/+ mice (with fluorescently labeled microglia and Purkinje cells) of both sexes were subcutaneously treated with a binge-level dose of ethanol (5.0 g/kg/day) or saline from postnatal days 4–9. Cranial windows were implanted in adolescent mice above the cerebellum to examine the long-term effects of developmental ethanol exposure on cerebellar microglia and Purkinje cell interactions using in vivo two-photon imaging.ResultsWe found that cerebellar microglia dynamics and morphology were not affected after developmental ethanol exposure. Microglia dynamics were also largely unaltered with respect to how they interact with Purkinje cells, although subtle changes in these interactions were observed in females in the molecular layer of the cerebellum.DiscussionThis work suggests that there are limited in vivo long-term effects of ethanol exposure on microglia morphology, dynamics, and neuronal interactions, so other avenues of research may be important in elucidating the mechanisms of FASD.

Purpose The aim of this study was to evaluate the efficacy and safety of radiofrequency ablation (RFA) in the management of haemorrhoidal disease with 1 year’s follow-up. Method This prospective multicentre study assessed RFA (Rafaelo©) in outpatients with grade II–III haemorrhoids. RFA was performed in the operating room under locoregional or general anaesthesia. Primary endpoint was the evolution of a quality-of-life score adapted to the haemorrhoid pathology (HEMO-FISS-QoL) 3 months after surgery. Secondary endpoints were evolution of symptoms (prolapsus, bleeding, pain, itching, anal discomfort), complications, postoperative pain and medical leave. Results A total of 129 patients (69% men, median age 49 years) were operated on in 16 French centres. Median HEMO-FISS-QoL score dropped significantly from 17.4/100 to 0/100 (p p p p Conclusion RFA is associated with an improvement in quality of life and symptoms with a good safety profile. As expected for minimally invasive surgery, postoperative pain is minor with short medical leave. Clinical trial registration and date Clinical trial NCT04229784 (18/01/2020).

The successful translation of gene therapy for clinical application will require the assessment of transgene activity as a measure of the biological function of a therapeutic transgene. Although current imaging permits the noninvasive detection of transgene expression, the critical need for quantitative imaging of the action of the expressed transgene has not been met. In vivo magnetic resonance spectroscopic imaging (MRSI) was applied to quantitatively delineate both the concentration and activity of a cytosine deaminase–uracil phosphoribosyltransferase (CD-UPRT) fusion enzyme expressed from a transgene. MRSI enabled the generation of anatomically accurate maps of the intratumoral heterogeneity in fusion enzyme activity. We observed an excellent association between the CD-UPRT concentration and activity and the percentage of CD-UPRT+ cells. Moreover, the regional levels of UPRT activity, as measured by imaging, correlated well with the biological affect of the enzyme. This study presents a translational imaging paradigm for precise, in vivo measurements of transgene activity with potential applications in both preclinical and clinical settings. [Cancer Res 2008;68(8):2878–84]

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Many natural forests in Southeast Asia are degraded following decades of logging. Restoration of these forests is delayed by ongoing logging and tropical cyclones, but the implications for recovery are largely uncertain. We analysed meteorological, satellite and forest inventory plot data to assess the effect of Typhoon Doksuri, a major tropical cyclone, on the forest landscapes of central Vietnam consisting of natural forests and plantations. We estimated the return period for a cyclone of this intensity to be 40 years. Plantations were almost twice as likely to suffer cyclone damage compared to natural forests. Logged natural forests (9–12 years after cessation of government-licensed logging) were surveyed before and after the storm with 2 years between measurements and remained a small biomass carbon sink (0.1 ± 0.3 Mg C ha −1 yr −1 ) over this period. The cyclone reduced the carbon sink of recovering natural forests by an average of 0.85 Mg C ha −1 yr −1 , less than the carbon loss due to ongoing unlicensed logging. Restoration of forest landscapes in Southeast Asia requires a reduction in unlicensed logging and prevention of further conversion of degraded natural forests to plantations, particularly in landscapes prone to tropical cyclones where natural forests provide a resilient carbon sink. This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.

Bi2O3 was proven an attractive compound for electrode modification in heavy metal electrochemical analysis. A novel method for synthesizing Bi2O3-attached multiwalled carbon nanotubes (Bi2O3@CNTs) in solution is successfully developed in this study. Characteristics of the obtained Bi2O3@CNTs were proven by modern techniques such as X-ray diffraction, Raman spectroscopy, scanning electronic microscopy, transmission electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and anodic stripping voltammetry. Microscopy images and spectra results reveal that Bi2O3 particles are mainly attached at defect points on multiwalled carbon nanotubes (MWCNTs) walls. Paste electrodes based on the MWCNTs and synthesized Bi2O3@CNTs were applied for electrochemical measurements. The redox mechanism of Bi2O3 on the electrode surface was also made clear by the cyclic voltammetric tests. The recorded cyclic voltammograms and electrochemical impedance spectroscopy demonstrate that the Bi2O3@CNTs electrode was in lower charge transfer resistance than the CNTs one and in the controlled diffusion region. Investigation on the electrochemical behavior of Pb2+ at the Bi2O3@CNTs electrodes found a significant improvement of analytical response, resulting in 3.44 μg/L of the detection limit and 2.842 μA/(μg/L) of the sensitivity with linear sweep anodic stripping voltammetry technique at optimized conditions.

Laser scanning is used in advanced biological microscopy to deliver superior imaging contrast, resolution and sensitivity. However, it is challenging to scale up the scanning speed required for interrogating a large and heterogeneous population of biological specimens or capturing highly dynamic biological processes at high spatiotemporal resolution. Bypassing the speed limitation of traditional mechanical methods, free-space angular-chirp-enhanced delay (FACED) is an all-optical, passive and reconfigurable laser-scanning approach that has been successfully applied in different microscopy modalities at an ultrafast line-scan rate of 1-80 MHz. Optimal FACED imaging performance requires optimized experimental design and implementation to enable specific high-speed applications. In this protocol, we aim to disseminate information allowing FACED to be applied to a broader range of imaging modalities. We provide (i) a comprehensive guide and design specifications for the FACED hardware; (ii) step-by-step optical implementations of the FACED module including the key custom components; and (iii) the overall image acquisition and reconstruction pipeline. We illustrate two practical imaging configurations: multimodal FACED imaging flow cytometry (bright-field, fluorescence and second-harmonic generation) and kHz 2D two-photon fluorescence microscopy. Users with basic experience in optical microscope operation and software engineering should be able to complete the setup of the FACED imaging hardware and software in ~2-3 months.

Received: 17.09.22. Revised: 15.10.22. Accepted: 16.10.22. Available online: 25.10.22. In this study, titanium dioxide (TiO2) and titanium dioxide – activated carbon composite (TiO2–AC) were prepared by sol-gel method for photoelectrochemical (PEC) applications. Characterization of the materials was performed by scanning electron microscope, energy dispersive X-ray analysis, Fourier transform infrared spectroscopy, X-ray diffraction, and diffuse reflectance spectroscopy. The results show that TiO2 was successfully loaded on activated carbon (AC), producing TiO2–AC with 2.61 eV of bandgap energy, lower than that of TiO2 (3.15 eV). Photoanodes based on TiO2 and TiO2–AC were fabricated and applied to PEC experiments for phenol degradation. In comparison with the TiO2 photoanode, the TiO2–AC one exhibited superior photocatalytic activity, which was indicated by a high current density and effective phenol removal. A mechanism of phenol PEC degradation on the TiO2–AC photoanode was proposed, which includes interaction between protonated phenol and active sites bearing oxygen on the photoanode surface. A kinetic model according to this mechanism was also established and fitted to experimental findings, resulting in rate constants of elementary reactions. This work was supported by the Vietnam’s Ministry of Natural Resources and Environment through project coded CS.2022.12.

The COVID-19 (COronaVIrus Disease) pandemic has been spreading globally and social isolation has been implemented as an effective solution to limit the spread of the pandemic before vaccines are de...

A new method for the quantitative description of the phase-specific localization of hybrid fillers in rubber blends was developed based on the wetting concept. Using the new concept, the kinetics of phase-specific localization of silica (Si)/carbon black (CB) hybrid fillers in styrene-butadiene rubber (SBR)/natural rubber (NR) blends was experimentally characterized during the single-step mixing and the multi-step mixing process. It could point out that the localization of the hybrid fillers at the end of the mixing process always reaches the stationary stage regardless of the mixing regime. The stationary state of filler localization is related to the migration of silica and CB during the mixing process, determined by the thermodynamic driving forces and well predicted by the Z model. The adsorption of the curing additives on the filler surface markedly alters the surface energy of silica and CB, which in turn influences the localization of hybrid fillers in rubber blends, particularly at low filler loading. That is why the morphological investigation made by electron microscopy for low filled rubber blends can hardly be applied to describe the filler localization of hybrid fillers in rubber blends at high filler loading.

Background: Radiation-induced scleral necrosis (RISN) is a rare, but a serious complication of brachytherapy for uveal melanoma. We aimed at analysing the incidence, timing and risk factors associated with development of RISN in a large institutional series. Methods: All consecutive cases with brachytherapy for uveal melanoma treated by the Departments of Ophthalmology and Radiotherapy at University Hospital Essen between 1999 and 2016 were eligible. Development of RISN during the post-treatment follow-up was recorded. A 1:2 propensity score matched case–control study was performed for the evaluation of the prognostic value of different tumour- and treatment-associated parameters. Results: RISN was documented in 115 (2.9%) of 3960 patients with uveal melanoma included in the final analysis, and occurred at the mean 30.3 months (range: 1.26–226 months) after brachytherapy. In the whole cohort, younger age (p = 0.042), plaque type (p = 0.001) and ciliary body involvement (p < 0.0001) were independently associated with the RISN occurrence. In the case–control study, multivariable weighted proportional hazard analysis discovered the association of the following additional tumour- and treatment-associated characteristics with RISN: posterior tumour margin anterior to equatorial region (p = 0.0003), extraocular tumour extension (p =

The health emergency linked to COVID-19 has been stressful for staff working in nursing home, doubly painful for residents faced with the risk of infection and the reality of family separation. We explore in this article some psychological consequences resulting from the experience of residents and caregivers in the waning health crisis, hoping that the experience gained will allow greater efficiency in the event of a resumption of the pandemic. At the same time, we proposed to combine this point of view with the more ethical one, taking seriously a fundamental tendency towards ageism in Western societies and what they reflect from the social ethics of care. It is now important to declare a refusal to "return to the abnormal", this medical and ethical prehistory, such as suffered by many of our elders and their caregivers during confinement.

Background Fibrosis-induced intestinal strictures leading to obstruction are a common and serious complication of Crohn’s disease (CD) with currently no available specific anti-fibrotic therapies. Cytoskeletal dynamics in mesenchymal cells are associated with organ fibrogenesis. Septin filaments are a novel cytoskeletal element, but the functional role of septins in regulating intestinal inflammation and fibrosis remain unknown. We examined the involvement of the septin cytoskeleton in modulating fibrogenic signaling in intestinal fibrogenesis in vitro and in vivo. Methods Expression of different septins in human intestinal resection tissues, primary human intestinal myofibroblasts (HIMF) and immortalized colonic myofibroblast (CCD 18co cells) were examined by real-time PCR and immunoblotting. Functional inhibition of the septin cytoskeleton was achieved using siRNA for septin 7 and the cell-permeable small molecule forchlorfenuron (FCF). Migration and proliferation of HIMF were examined by wound healing and thymidine incorporation assays, respectively. Levels of secreted cytokines were measured using cytometric bead array. Roles of septins in the development intestinal fibrosis in vivo was studied using a chronic DSS colitis model in mice with administration of FCF or vehicle. Results All septin genes were expressed in intestinal tissues with a predominant expression of septin 7. Pro-fibrotic transforming growth factor-β1 (TGFβ1) triggered HIMF activation manifested by the increased production of ECM proteins such as fibronectin and collagen 1 and enhanced expression of the myofibroblast markers α-smooth muscle actin, L-caldesmon and tropomyosin. Septin 7 knockdown resulted in loss of other septin proteins thereby disrupting the entire septin cytoskeleton. Either pharmacological, or genetic disruption of the septin cytoskeleton reversed the effect of TGFβ1 by attenuating production of ECM proteins and reducing expression of myofibroblast markers. Interestingly, these effects were only found on protein level and were not due to changes in gene expression, suggesting inhibition of their expression at a post-transcriptional level. Moreover, pharmacological or genetic disruptions of the septin cytoskeleton resulted in reduced migration, and attenuated cytokine secretion by activated myofibroblasts. FCF administration did not affect intestinal inflammation, but decreased the fibrosis score during chronic DSS colitis in mice. Conclusion Our data highlights the septin cytoskeleton as a novel regulator of intestinal myofibroblast activation and function. This for the first time implicates the cytoskeleton as an active participant in intestinal fibrosis and as a potential novel target for the development of anti-fibrotic therapies in IBD patients.

Background Mesenteric fat wrapping around the intestinal wall, so called ‘creeping fat’ (CF), is spatially linked with stricture formation in Crohn’s disease (CD). Intestinal muscularis propria (MP) smooth muscle cell (HIMC) hyperplasia is a major contributor to luminal narrowing in stricturing CD. We investigated CF derived factors and their effect on HIMC hyperplasia in vitro and in vivo using human tissues, primary human cells and a colitis model. Methods Secretion of free fatty acids (FFA) by mesenteric fat (MF) or CF organ cultures was determined via lipidomic mass spectrometry. Effects of different length and types of FFA as well as CF and MF conditioned medium on proliferation of primary HIMF was assessed. Next generation sequencing (NGS) and lipidomics on HIMF was performed and relevant pathways inhibited with small molecules or siRNA knockdown. In the dextrane sodium sulfate (DSS) induced colitis model CPT-1 blockade was achieved via the small molecule etomoxir. Results Histopathology analysis of intestinal resection tissues revealed CD CF being located in the subserosa and its presence was linked with dramatic thickening of the MP. CF conditioned medium markedly upregulated HIMC proliferation compared to mesenteric fat from CD, UC and normal controls. CF released higher amounts of total, saturated and poly-unsaturated FFA with elevated levels of five long-chain (LC-)FFA, including palmitate. LC, but not medium or short chain FFA selectively increased proliferation in HIMC and fibroblasts, but not other intestinal cell types. NGS revealed gene regulation suggesting LC-FFA transport as a putative mechanism. Lipidomic analysis indicated the majority of palmitate being converted into phospholipids, predominantly phosphatidylcholine. Inhibition of LC-FFA uptake into cells via CD36, metabolism through inhibition of acyl-CoA synthetase, choline-phosphate cytidylyltransferase & choline kinase or blockade of LC-FFA uptake into mitochondria through CPT-1A reduced palmitate and CF conditioned medium induced HIMC proliferation. MP thickness increased in acute DSS colitis. Prophylactic inhibition of CPT-1 with etomoxir in acute DSS colitis did not reduce histopathologic inflammation or inflammatory cytokine gene expression, but reduced MP thickness and gene expression of the smooth muscle cell genes desmin and Sm22. Conclusion Subserosal CF releases LC-FFA inducing a selective proliferative response by HIMC. This effect was dependent on CD36, acyl-CoA synthetase and CPT-1. LC-FFA in HIMC are converted into phospholipids. Inhibtion of CPT-1 in DSS colitis reduced the increased MP thickness. These results point to CF as a novel contributor to stricture formation in CD.

This study deals with the preparation and characterization of platinum/reduced graphene oxide (Pt/rGO) as an efficient cathode for dye-sensitized solar cells. Herein, the Pt/rGO material was synthesized by co-precipitation from hexachloroplatinic acid (H2PtCl6) and graphene oxide (GO) precursors. The fabrication of cathodes from Pt/rGO composite paste was carried out using screen-printing paste. The electrochemical behaviors of as-prepared cathodes were analyzed by cyclic voltammetry; the performance of fabricated DSSCs was measured by current density–voltage (J-V) curves and electrochemical impedance spectroscopy. The structural characteristics of the Pt/rGO binary composites were confirmed by Fourier-transform infrared spectroscopy, Raman spectroscopy, x-ray diffraction (XRD), and transmission electron microscopy. Empirical data showed that choosing ascorbic acid as a reducing agent at a ratio of 5:1 between ascorbic acid weight and precursor mixture weight, as well as a GO weight percentage of 20% fabricated DSSCs successfully with a conversion efficiency of 6.25%, which was approximately 90% compared to that of pure commercial Pt material. Characterization results indicated that the Pt nanoparticles were homogeneously distributed on the rGO sheets with an average diameter of less than 25 nm. The Pt/rGO hybrid composite is highly expected to replace Pt in the fabrication of cathodes in DSSCs for low-cost DSSC production in the promising future.

Im Rahmen des vom BMWi geförderten Forschungsprojektes „SmartAdapt“ (FK-03ET1431A) [1] werden an der Beuth Hochschule für Technik Berlin mehrere Prüfstände für hydraulische und thermische Untersuchungen an heiztechnischen Anlagen entwickelt und betrieben. Neben der Anwendung in der Forschung ermöglichen die Prüfstände den Einsatz sowohl in der Lehre als auch für Technologietransfer/Dienstleistungen. Im Fokus der aktuellen Forschung stehen insbesondere die Praxiserprobung und die Weiterentwicklung eines adaptiven Regelalgorithmus zur Betriebsoptimierung von Heizungsanlagen. Dieser wurde bereits im Vorgängerprojekt (FK-03ET1150A) entwickelt und umfassend validiert [2], [3].

International audience; Purpose: The purpose of this study was to assess the performance of magnetic resonance imaging (MRI) in children and adolescents with suspected adnexal torsion (AT) after inconclusive initial ultrasound examination.Materials and methods: Twenty-eight girls with a mean age of 12±4 (SD) years (range: 1 month to 18years) were included. All had clinically suspected AT and inconclusive initial ultrasound findings followed by pelvic MRI as a second-line imaging modality. The final diagnosis was obtained by surgery or follow-up. Two radiologists blinded to the clinical, ultrasound and surgical data, retrospectively and independently reviewed MRI examinations. Clinical and MRI features associated with AT were searched for using univariate analyses.Result: Among the 28 patients, 10/28 patients (36%) had AT and 22/28 (79%) had an ovarian or tubal mass. AT was associated with an age

We report a method for coupling of nitroarenes, 2- or 4-methylazaarenes, and elemental sulfur to afford (2-pyridyl)aryl thioamides. Good tolerance of functionalities was observed, including primary...