bluuebunny/crossref_metadata_2025 huggingface dataset:
Endurance exercise training restores diabetes-induced alteration in circulating Glycosylphosphatidylinositol-specific phospholipase D levels in rats
Authors: Abdolmaleki Farzad , Heidarianpour Ali
Published: May 2020

Background

Glycosylphosphatidylinositol-specific phospholipase D (GPLD1) is responsible for cleaving membrane-associated glycosylphosphatidylinositol (GPI) molecules, which is affected by diabetes. We aimed to examine the effect of 14 weeks treadmill running on serum GPLD1 levels and its association with glycemic indexes and serum glypican-4 (GPC-4), a novel GPI-anchored adipokine, in streptozotocin-nicotinamide-induced diabetic rats.

Methods

Thirty-six male Wister rats were randomly divided into three groups of twelve animals each, involving sedentary control (SC), sedentary diabetic (SD), and trained diabetic (TD) groups. The diabetes was induced through intraperitoneal injection of 120 mg/kg nicotinamide 15 min prior to intraperitoneal injection of 65 mg/kg streptozotocin in SD and TD groups. The TD group was exercised on a treadmill for 60 min/days, 5 days/wk at 26 m/min, and zero grade for 14 weeks. Following the experiment period, blood samples were taken from all animals and analyzed for experimental indexes via sandwich ELISA.

Results

Exercise training caused a significant decrease in the elevated blood glucose levels and a significant increase in the lowered blood insulin levels in TD rats (both p < 0.001). Glucose tolerance of TD rats significantly improved following experimental protocol, as indicated by OGTT (p < 0.001). Experimental diabetes significantly increased serum GPLD1 levels (p < 0.001), while exercise training significantly decreased its levels (p < 0.001). Serum GPLD1 levels correlated directly with glycemic indexes involving FBS, 2hOGTT, and AUC of glucose (r = 0.80, r = 0.79, r = 0.79, respectively, all p < 0.001) and inversely with serum insulin levels (r = − 0.83, p < 0.001). There were no significant differences in serum GPC-4 levels among groups, and no association with GPLD1 alteration.

Conclusions

Sedentary diabetic rats have higher circulating GPLD1 compared to controls, which can be reversed by exercise training and is associated with modifying in glycemic and insulin profile.
Novel HDAC inhibitor MAKV-8 and imatinib synergistically kill chronic myeloid leukemia cells via inhibition of BCR-ABL/MYC-signaling: effect on imatinib resistance and stem cells
Authors: Lernoux Manon , Schnekenburger Michael , Losson Hélène , Vermeulen Koen , Hahn Hyunggu , Gérard Déborah , Lee Jin-Young , Mazumder Aloran , Ahamed Muneer , Christov Christo , Kim Dong-Wook , Dicato Mario , Bormans Guy , Han Byung Woo , Diederich Marc
Published: May 2020

Background

Chronic myeloid leukemia (CML) pathogenesis is mainly driven by the oncogenic breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) fusion protein. Since BCR-ABL displays abnormal constitutive tyrosine kinase activity, therapies using tyrosine kinase inhibitors (TKis) such as imatinib represent a major breakthrough for the outcome of CML patients. Nevertheless, the development of TKi resistance and the persistence of leukemia stem cells (LSCs) remain barriers to cure the disease, justifying the development of novel therapeutic approaches. Since the activity of histone deacetylase (HDAC) is deregulated in numerous cancers including CML, pan-HDAC inhibitors may represent promising therapeutic regimens for the treatment of CML cells in combination with TKi.

Results

We assessed the anti-leukemic activity of a novel hydroxamate-based pan-HDAC inhibitor MAKV-8, which complied with the Lipinski’s “rule of five,” in various CML cells alone or in combination with imatinib. We validated the in vitro HDAC-inhibitory potential of MAKV-8 and demonstrated efficient binding to the ligand-binding pocket of HDAC isoenzymes. In cellulo, MAKV-8 significantly induced target protein acetylation, displayed cytostatic and cytotoxic properties, and triggered concomitant ER stress/protective autophagy leading to canonical caspase-dependent apoptosis. Considering the specific upregulation of selected HDACs in LSCs from CML patients, we investigated the differential toxicity of a co-treatment with MAKV-8 and imatinib in CML versus healthy cells. We also showed that beclin-1 knockdown prevented MAKV-8-imatinib combination-induced apoptosis. Moreover, MAKV-8 and imatinib co-treatment synergistically reduced BCR-ABL-related signaling pathways involved in CML cell growth and survival. Since our results showed that LSCs from CML patients overexpressed c-MYC, importantly MAKV-8-imatinib co-treatment reduced c-MYC levels and the LSC population. In vivo, tumor growth of xenografted K-562 cells in zebrafish was completely abrogated upon combined treatment with MAKV-8 and imatinib.

Conclusions

Collectively, the present findings show that combinations HDAC inhibitor-imatinib are likely to overcome drug resistance in CML pathology.
ALICAT: a customized approach to item selection process in computerized adaptive testing
Authors: G. Jatobá Victor M. , Farias Jorge S. , Freire Valdinei , Ruela André S. , Delgado Karina V.
Published: May 2020

Computerized adaptive testing (CAT) based on item response theory allows more accurate assessments with fewer questions than the classic paper and pencil (P&P) test. Nonetheless, the CAT construction involves some key questions that, when done properly, can further improve the accuracy and efficiency in estimating the examinees’ abilities. One of the main questions is in regard to choosing the item selection rule (ISR). The classic CAT makes exclusive use of one ISR. However, these rules have differences depending on the examinees’ ability level and on the CAT stage. Thus, the objective of this work is to reduce the dichotomous test size which is inserted in a classic CAT with no significant loss of accuracy in the estimation of the examinee’s ability level. For this purpose, we analyze the ISR performance and then build a personalized item selection process in CAT considering the use of more than one rule. The case study in Mathematics and its Technologies test of the ENEM 2012 shows that the Kullback-Leibler information with a posterior distribution (KLP) has better performance in the examinees’ ability estimation when compared with Fisher information (F), Kullback-Leibler information (KL), maximum likelihood weighted information (MLWI), and maximum posterior weighted information (MPWI) rules. Previous results in the literature show that CAT using KLP was able to reduce this test size by 46.6% from the full size of 45 items with no significant loss of accuracy in estimating the examinees’ ability level. In this work, we observe that the F and the MLWI rules performed better on early CAT stages to estimate examinees’ proficiency level with extreme negative and positive values, respectively. With this information, we were able to reduce the same test by 53.3% using the personalized item selection process, called ALICAT, which includes the best rules working together.
γ-Secretase modulators exhibit selectivity for modulation of APP cleavage but inverse γ-secretase modulators do not
Authors: Lessard Christian B. , Rodriguez Edgardo , Ladd Thomas B. , Minter Lisa M. , Osborne Barbara A. , Miele Lucio , Golde Todd E. , Ran Yong
Published: May 2020

Background

γ-Secretase is a multiprotein protease that cleaves amyloid protein precursor (APP) and other type I transmembrane proteins. It has two catalytic subunits, presenilins 1 and 2 (PS1 and 2). In our previous report, we observed subtle differences in PS1- and PS2-mediated cleavages of select substrates and slightly different potencies of PS1 versus PS2 inhibition for select γ-secretase inhibitors (GSIs) on various substrates. In this study, we investigated whether γ-secretase modulators (GSMs) and inverse γ-secretase modulators (iGSMs) modulate γ-secretase processivity using multiple different substrates. We next used HEK 293T cell lines in which PSEN1 or PSEN2 was selectively knocked out to investigate processivity and response to GSMs and iGSMs.

Methods

For cell-free γ-secretase cleavage assay, recombinant substrates were incubated with CHAPSO-solubilized CHO or HEK 293T cell membrane with GSMs or iGSMs in suitable buffer. For cell-based assay, cDNA encoding substrates were transfected into HEK 293T cells. Cells were then treated with GSMs or iGSMs, and conditioned media were collected. Aβ and Aβ-like peptide production from cell-free and cell-based assay were measured by ELISA and mass spectrometry.

Result

These studies demonstrated that GSMs are highly selective for effects on APP, whereas iGSMs have a more promiscuous effect on many substrates. Surprisingly, iGSMs actually appear to act as like GSIs on select substrates. The data with PSEN1 or PSEN2 knocked out HEK 293T reveal that PS1 has higher processivity and response to GSMs than PS2, but PS2 has higher response to iGSM.

Conclusion

Collectively, these data indicate that GSMs are likely to have limited target-based toxicity. In addition, they show that iGSMs may act as substrate-selective GSIs providing a potential new route to identify leads for substrate-selective inhibitors of certain γ-secretase-mediated signaling events. With growing concerns that long-term β-secretase inhibitor is limited by target-based toxicities, such data supports continued development of GSMs as AD prophylactics.
Dynamic MRI for articulating joint evaluation on 1.5 T and 3.0 T scanners: setup, protocols, and real-time sequences
Authors: Garetier Marc , Borotikar Bhushan , Makki Karim , Brochard Sylvain , Rousseau François , Ben Salem Douraïed
Published: May 2020

Dynamic magnetic resonance imaging (MRI) is a non-invasive method that can be used to increase the understanding of the pathomechanics of joints. Various types of real-time gradient echo sequences used for dynamic MRI acquisition of joints include balanced steady-state free precession sequence, radiofrequency-spoiled sequence, and ultra-fast gradient echo sequence. Due to their short repetition time and echo time, these sequences provide high temporal resolution, a good signal-to-noise ratio and spatial resolution, and soft tissue contrast. The prerequisites of the evaluation of joints with dynamic MRI include suitable patient installation and optimal positioning of the joint in the coil to allow joint movement, sometimes with dedicated coil support. There are currently few recommendations in the literature regarding appropriate protocol, sequence standardizations, and diagnostic criteria for the use of real-time dynamic MRI to evaluate joints. This article summarizes the technical parameters of these sequences from various manufacturers on 1.5 T and 3.0 T MRI scanners. We have reviewed pertinent details of the patient and coil positioning for dynamic MRI of various joints. The indications and limitations of dynamic MRI of joints are discussed.
Evaluation of the bronchial arteries: normal findings, hypertrophy and embolization in patients with hemoptysis
Authors: Almeida João , Leal Cecília , Figueiredo Luísa
Published: May 2020

The enlargement of the bronchial arteries occurs in a multitude of congenital and acquired diseases and is responsible for the majority of cases of hemoptysis. In this review, we provide a simplified imaging approach to the evaluation of the bronchial arteries. We highlight the anatomy and function of the bronchial arteries, typical imaging findings, how to recognize bronchial artery dilatation, and its underlying causes. Contrast-enhanced computer tomography plays a major role in diagnosing bronchial artery enlargement and also improves treatment planning. Bronchial artery embolization has proven to be effective in controlling the potential hazardous hemoptysis.
Survivability-aware routing restoration mechanism for smart grid communication network in large-scale failures
Authors: Liu Bao Ju , Yu Peng , Xue-song Qiu , Shi Lei
Published: May 2020

Natural disasters such as earthquakes have consecutive impacts on the smart grid because of aftershock activities. To guarantee service requirements and smart grid stable operations, it is a challenge to design a fast and survivable rerouting mechanism. There are few studies that consider concurrent rerouting aiming at multiple services in smart grid communication network, however. Firstly, we formulate the node survivability, link survivability, and path survivability model in terms of the distance from the epicenter to the node and the link of the network. Meanwhile, we introduce the indicator of site difference level which is unique in the smart grid to further restrict the service path. Secondly, to improve the algorithm efficiency and reduce rerouting time, the deep first search algorithm is utilized to obtain the available rerouting set, and then the I-DQN based on the framework of reinforcement learning is proposed to achieve concurrent rerouting for multiple services. The experimental results show that our approach has a better convergence performance and higher survivability as well as the approximate latency in comparison with other approaches.
Stability analysis for boundary value problems with generalized nonlocal condition via Hilfer–Katugampola fractional derivative
Authors: Ahmed Idris , Kumam Poom , Jarad Fahd , Borisut Piyachat , Sitthithakerngkiet Kanokwan , Ibrahim Alhassan
Published: May 2020

In this research, we present the stability analysis of a fractional differential equation of a generalized Liouville–Caputo-type (Katugampola) via the Hilfer fractional derivative with a nonlocal integral boundary condition. Besides, we derive the relation between the proposed problem and the Volterra integral equation. Using the concepts of Banach and Krasnoselskii’s fixed point theorems, we investigate the existence and uniqueness of solutions to the proposed problem. Finally, we present two examples to clarify the abstract result.
Patient experience of health and care when undergoing colorectal surgery within the ERAS program
Authors: Wennström Berith , Johansson Anna , Kalabic Sabina , E-son Loft Anna-Lena , Skullman Stefan , Bergh Ingrid
Published: May 2020

Background

Several studies show that the enhanced recovery after surgery (ERAS) program reduces complications postoperatively and leads to faster recovery and shorter hospital stays. However, little is known about patients’ self-reported health in an enhanced recovery context. The aim of this study was firstly to describe patient experiences of health within the concept of ERAS after colorectal (CR) surgery during a hospital stay and within 2 weeks of discharge. Secondly, to explore whether the ASA classification/co-morbidity, sex, and surgical method affect the patient’s experience of health.

Methods

Data were collected through the ERAS-HEALTH questionnaire, including two open-ended questions, and through telephone interviews postoperatively. Qualitative and quantitative analysis was used. Patients undergoing CR surgery (n = 80) were included from October 2016 to June 2018.

Results

The patients had mainly positive experiences of their hospital stay as well as most of them felt comfortable coming home. However, experienced state of health is affected by factors like surgical method and co-morbidity. Improvements were desired concerning information, food/food intake, pain management, and environment. At home, the patients experienced a lack of information about food/food intake and ostomy care. Decreased appetite and difficulties with micturition were also described. The most troublesome symptom was postoperative fatigue (POF). Analysis of the ERAS-HEALTH questionnaire showed that patients with higher co-morbidity and those who underwent open surgery have a significantly worse experience of their health compared with patients who underwent laparoscopy. However, it seems that the surgical method affects postoperative health to a greater extent than co-morbidity.

Conclusions

The patients reported many positive aspects and challenges when being cared for within the ERAS program. However, several improvements are needed to satisfy patient wishes regarding their care both in hospital and at home. Laparoscopic surgery affects patient state of health positively in several respects compared with open surgery.
Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy
Authors: Kempthorne Liam , Yoon Hyejin , Madore Charlotte , Smith Scott , Wszolek Zbigniew K. , Rademakers Rosa , Kim Jungsu , Butovsky Oleg , Dickson Dennis W.
Published: May 2020

Microglia are resident macrophages of the central nervous system, and their unique molecular signature is dependent upon CSF-1 signaling. Previous studies have demonstrated the importance of CSF-1R in survival and development of microglia in animal models, but the findings are of uncertain relevance to understanding the influence of CSF-1R on microglia in humans. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) [also known as adult onset leukoencephalopathy with spheroids and pigmented glia (ALSP)] is a neurodegenerative disorder primarily affecting cerebral white matter, most often caused by mutations of CSF1R. Therefore, we hypothesized that the molecular profile of microglia may be affected in HDLS. Semi-quantitative immunohistochemistry and quantitative transcriptomic profiling revealed reduced expression of IBA-1 and P2RY12 in both white and gray matter microglia of HDLS. In contrast, there was increased expression of CD68 and CD163 in microglia in affected white matter. In addition, expression of selective and specific microglial markers, including P2RY12, CX3CR1 and CSF-1R, were reduced in affected white matter. These results suggest that microglia in white matter in HDLS lose their homeostatic phenotype. Supported by gene ontology analysis, it is likely that an inflammatory phenotype is a key pathogenic feature of microglia in vulnerable brain regions of HDLS. Our findings suggest a potential mechanism of disease pathogenesis by linking aberrant CSF-1 signaling to altered microglial phenotype. They also support the idea that HDLS may be a primary microgliopathy. We observed increased expression of CSF-2 in gray matter compared to affected white matter, which may contribute to selective vulnerability of white matter in HDLS. Our findings suggest that methods that restore the homeostatic phenotype of microglia might be considered treatment approaches in HDLS.
Radiation doses from 161Tb and 177Lu in single tumour cells and micrometastases
Authors: Alcocer-Ávila Mario E. , Ferreira Aymeric , Quinto Michele A. , Morgat Clément , Hindié Elif , Champion Christophe
Published: May 2020

Background

Targeted radionuclide therapy (TRT) is gaining importance. For TRT to be also used as adjuvant therapy or for treating minimal residual disease, there is a need to increase the radiation dose to small tumours. The aim of this in silico study was to compare the performances of 161Tb (a medium-energy β− emitter with additional Auger and conversion electron emissions) and 177Lu for irradiating single tumour cells and micrometastases, with various distributions of the radionuclide.

Methods

We used the Monte Carlo track-structure (MCTS) code CELLDOSE to compute the radiation doses delivered by 161Tb and 177Lu to single cells (14 μm cell diameter with 10 μm nucleus diameter) and to a tumour cluster consisting of a central cell surrounded by two layers of cells (18 neighbours). We focused the analysis on the absorbed dose to the nucleus of the single tumoral cell and to the nuclei of the cells in the cluster. For both radionuclides, the simulations were run assuming that 1 MeV was released per μm3 (1436 MeV/cell). We considered various distributions of the radionuclides: either at the cell surface, intracytoplasmic or intranuclear.

Results

For the single cell, the dose to the nucleus was substantially higher with 161Tb compared to 177Lu, regardless of the radionuclide distribution: 5.0 Gy vs. 1.9 Gy in the case of cell surface distribution; 8.3 Gy vs. 3.0 Gy for intracytoplasmic distribution; and 38.6 Gy vs. 10.7 Gy for intranuclear location. With the addition of the neighbouring cells, the radiation doses increased, but remained consistently higher for 161Tb compared to 177Lu. For example, the dose to the nucleus of the central cell of the cluster was 15.1 Gy for 161Tb and 7.2 Gy for 177Lu in the case of cell surface distribution of the radionuclide, 17.9 Gy for 161Tb and 8.3 Gy for 177Lu for intracytoplasmic distribution and 47.8 Gy for 161Tb and 15.7 Gy for 177Lu in the case of intranuclear location.

Conclusion

161Tb should be a better candidate than 177Lu for irradiating single tumour cells and micrometastases, regardless of the radionuclide distribution.
Addressing soil protection concerns in forest ecosystem management under climate change
Authors: Rodrigues Ana Raquel , Botequim Brigite , Tavares Catarina , Pécurto Patrícia , Borges José G.
Published: May 2020

Background

Climate change may strongly influence soil erosion risk, namely through variations in the precipitation pattern. Forests may contribute to mitigate the impacts of climate change on soil erosion and forest managers are thus challenged by the need to define strategies that may protect the soil while addressing the demand for other ecosystem services. Our emphasis is on the development of an approach to assess the impact of silvicultural practices and forest management models on soil erosion risks under climate change. Specifically, we consider the annual variation of the cover-management factor (C) in the Revised Universal Soil Loss Equation over a range of alternative forest management models to estimate the corresponding annual soil losses, under both current and changing climate conditions. We report and discuss results of an application of this approach to a forest area in Northwestern Portugal where erosion control is the most relevant water-related ecosystem service.

Results

Local climate change scenarios will contribute to water erosion processes, mostly by rainfall erosivity increase. Different forest management models provide varying levels of soil protection by trees, resulting in distinct soil loss potential.

Conclusions

Results confirm the suitability of the proposed approach to address soil erosion concerns in forest management planning. This approach may help foresters assess management models and the corresponding silvicultural practices according to the water-related services they provide.
Differences in community composition of endophytic fungi between above- and below-ground tissues of Aristolochia chilensis in an arid ecosystem
Authors: Guevara-Araya M. J. , Vilo C. , Urzúa A. , González-Teuber M.
Published: May 2020

Background

Endophytic fungi are diverse and ubiquitous in nature, yet studies simultaneously comparing endophyte communities in above- and below-ground plant tissues are relatively scarce. The main goal of our study was to compare the diversity and community composition of endophytic fungi associated with above- and below-ground tissues of the plant Aristolochia chilensis in an arid ecosystem. Endophytic fungi were isolated from healthy leaves and roots of A. chilensis, and the internal transcribed spacer (ITS) region was sequenced for phylogenetic and taxonomic analysis.

Results

A combined total of 457 fungal isolates were cultured from leaf and root tissues, belonging to 54 operational taxonomic units (OTUs). The genera Fusarium, Penicillium, Phialemonium and Trichoderma were the most representative endophyte taxa identified in A. chilensis tissues; nevertheless, Fusarium was significantly more dominant in the below-ground community, while foliar endophyte community was dominated by Penicillium. Whereas OTU richness and diversity were not different between below-ground and above-ground tissues, endophyte abundance was on average twice as high in below-ground tissue than in above-ground tissue. Fungal endophyte communities in the two tissue types were significantly dissimilar.

Conclusions

Results from this study indicate that A. chilensis harbors a similar diversity of endophytic fungi in above- and below-ground tissues. Dominant endophytic fungi were found to be dependent on tissue type, which potentially resulted in marked differences in community structure between above- and below-ground tissues. Ecological processes potentially affecting this pattern are discussed.
Multi-ethnic validation of 15-item Geriatric Depression Scale in Chile
Authors: Gallardo-Peralta Lorena P. , Rodríguez-Blázquez Carmen , Ayala-García Alba , Forjaz María João
Published: May 2020

Background

There has been scant research published regarding the assessment of depression in ethnic groups, and few studies have addressed the validation of scales for standardized assessment of depressive symptoms among indigenous minorities.

Objective

The aim of this study was to analyze the psychometric properties of the 15-item Geriatric Depression Scale (GDS-15) for a multi-ethnic sample of older Chilean adults.

Methods

Cross-sectional study with a sample of 800 older people, 71% of whom were self-declared indigenous (Aymara/Mapuche).

Results

The non-indigenous group had a higher total GDS-15 score and lower quality of life and wellbeing scores than the indigenous groups (p < 0.001). The GDS-15 had a KR-20 coefficient of 0.90 for the non-indigenous group, 0.80 for Aymara, and 0.85 for Mapuche. The homogeneity index was 0.38 for non-indigenous, 0.24 for Aymara, and 0.29 for Mapuche.

Discussion

The GDS-15 showed satisfactory psychometric characteristics for the samples studied. However, the better results observed for the non-indigenous group suggest that some characteristics and content of the rating scale are not fully appropriate for the indigenous older population.

Conclusions

There is a need to develop the transcultural validation of scales such as GDS-15, which are applied in a standardized manner in geriatric evaluations as part of primary healthcare.
Predictors of problematic smartphone use among university students
Authors: Laurence Paulo Guirro , Busin Yuri , da Cunha Lima Helena Scoz , Macedo Elizeu Coutinho
Published: May 2020

Predictors of problematic smartphone use have been found mainly in studies on elementary and high school students. Few studies have focused on predictors related to social network and messaging apps or smartphone model. Thus, the objective of our study was to identify predictors of problematic smartphone use related to demographic characteristics, loneliness, social app use, and smartphone model among university students. This cross-sectional study involved 257 Brazilian university students who answered a smartphone addiction scale, a questionnaire about smartphone usage patterns, and the Brazilian version of the UCLA-R loneliness scale. Women, iPhone owners, and users of Instagram and Snapchat had significantly higher smartphone addiction scores. We found correlations between scores for the Brazilian version of smartphone addiction scale and the importance attributed to WhatsApp, Facebook, Instagram, and Snapchat, and the Brazilian version of the UCLA-R loneliness scale. Our hierarchical regression model predicted 32.2% of the scores of the Brazilian version of the smartphone addiction scale, with the greatest increase in predictive capability by the step that added smartphone social app importance, followed by the step that added loneliness. Adding the smartphone model produced the smallest increase in predictive capability. The theoretical and practical implications of these results are discussed.
Obstructive lung disease and quality of life after cure of multi-drug-resistant tuberculosis in Uganda: a cross-sectional study
Authors: Nuwagira Edwin , Stadelman Anna , Baluku Joseph Baruch , Rhein Joshua , Byakika-Kibwika Pauline , Mayanja Harriet , Kunisaki Ken M.
Published: May 2020

Background

Pulmonary multi-drug-resistant tuberculosis (MDR TB) alters lung architecture and involves lengthy treatment duration, high pill burden, drug adverse effects, travel restrictions, and stigma. Literature about pulmonary function and health-related quality of life (QoL) of patients treated for MDR TB is limited. This study sought to determine the prevalence of chronic obstructive pulmonary disease (COPD) and QoL of patients who were treated for pulmonary MDR TB.

Methods

Participants who completed 18 months of pulmonary MDR TB treatment and considered cured were eligible to be evaluated in a cross-sectional study. We performed post-bronchodilator spirometry to measure forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). COPD was defined as FEV1/FVC < 0.7; health-related QoL was assessed using the Medical Outcomes Survey for HIV (MOS-HIV) and St. George’s Respiratory Questionnaire (SGRQ). Linear and logistic regression models were used to assess associations with COPD, health-related QoL, and other characteristics of the cohort.

Results

A total of 95 participants were enrolled. Median age of the cohort was 39 years (interquartile range (IQR), 29–45), and 55 (58%) were HIV-positive. COPD prevalence was 23% (22/95). Median SGRQ score was normal at 7.8 (IQR, 3.1–14.8). Median mental and physical health summary scores were significantly impaired, at 58.6 (IQR, 52.0–61.5) and 52.9 (IQR, 47.8–57.9), respectively, on a scale of 0 to 100 where 100 represents excellent physical or mental health. In this sample, 19% (18/95) of participants were in the lowest relative socioeconomic position (SEP) while 34% (32/95) were in the highest relative SEP. Belonging in the lowest SEP group was the strongest predictor of COPD.

Conclusion

Individuals who have completed MDR TB treatment have a high prevalence of COPD and low mental and physical health summary scores. Our study highlights the need for pulmonary rehabilitation programs in patients with a low socioeconomic position (SEP) after MDR TB treatment.
3D printing of high performance polymer-bonded PEEK-NdFeB magnetic composite materials
Authors: Pigliaru L. , Rinaldi M. , Ciccacci L. , Norman A. , Rohr T. , Ghidini T. , Nanni F.
Published: May 2020

Permanent Rare Earth magnets are becoming more and more important in efficient motors and generators with high energy density. Among them NdFeB magnets are the most employed, with NdFeB having higher remanence, high coercivity and energy product. Nevertheless,their poor corrosion resistance makes them susceptible to degradation of the magnetic properties. One possible solution is the development of innovative polymeric composite magnetic materials. The preparation of NdFeB powders filled polymeric matrix (PEEK), with a double goal of protecting the magnetic alloy is proposed, thus preventing it from corrosion, and to realize a new material that can be shaped in the form of filaments. This material was used as feedstock in the 3D printing process to produce high performance magnets with customized and optimized design. The PEEK-NdFeB filaments were produced with three percentages of filler amount(i.e. 25, 50 and 75 wt%). PEEK neat filaments were produced as reference. The influence of the filler on the main thermomechanical properties of the resulting composites, as well as its effect onthe 3D printing process were evaluated by means of different investigation techniques (DSC, DMTA, XRD, tensile testing). The magnetic properties exhibited by Fused Filament Fabrication (FFF) printed parts confirmed the feasibility of employing such a combination of an innovative manufacturing technique and high-performance PEEK-NdFeB compounds.

The characterization carried out on both neat and composite filaments evidenced that the presence of the filler slightly decreased the thermal stability, increased the elastic modulus while decreasing ductility and maximum tensile strength. By means of DSC analysis, it was confirmed that the crystallinity is influenced by the presence of the filler. Magnetic measurement performed on the 3D printed parts demonstrate that interesting magnetic properties were achieved, confirming the feasibility of the magnetic 3D printed composite with PEEK.
Impact of dissociation on the effectiveness of psychotherapy for post-traumatic stress disorder: meta-analysis
Authors: Hoeboer C. M. , De Kleine R. A. , Molendijk M. L. , Schoorl M. , Oprel D. A. C. , Mouthaan J. , Van der Does W. , Van Minnen A.
Published: May 2020

Background

Many patients with post-traumatic stress disorder (PTSD) experience dissociative symptoms. The question of whether these dissociative symptoms negatively influence the effectiveness of psychotherapy for PTSD is unresolved.

Aims

To determine the influence of dissociative symptoms on psychotherapy outcome in PTSD.

Method

We conducted a systematic search in Cochrane, Embase, PILOTS, PsycINFO, PubMed and Web of Science for relevant clinical trials. A random-effects meta-analysis examined the impact of dissociation on psychotherapy outcome in PTSD (pre-registered at Prospero CRD42018086575).

Results

Twenty-one trials (of which nine were randomised controlled trials) with 1714 patients were included. Pre-treatment dissociation was not related to treatment effectiveness in patients with PTSD (Pearson's correlation coefficient 0.04, 95% CI −0.04 to 0.13). Between-study heterogeneity was high but was not explained by moderators such as trauma focus of the psychotherapy or risk of bias score. There was no indication for publication bias.

Conclusions

We found no evidence that dissociation moderates the effectiveness of psychotherapy for PTSD. The quality of some of the included studies was relatively low, emphasising the need for high-quality clinical trials in patients with PTSD. The results suggest that pre-treatment dissociation does not determine psychotherapy outcome in PTSD.
Evaluation of the Physico-mechanical Properties and Electrostatic Charging Behavior of Different Capsule Types for Inhalation Under Distinct Environmental Conditions
Authors: Pinto Joana T. , Wutscher Thomas , Stankovic-Brandl Milica , Zellnitz Sarah , Biserni Stefano , Mercandelli Alberto , Kobler Mirjam , Buttini Francesca , Andrade Laura , Daza Veronica , Ecenarro Susana , Canalejas Laura , Paudel Amrit
Published: May 2020

Capsule-based dry powder inhaler (DPI) products can be influenced by a multitude of interacting factors, including electrostatic charging. Tribo-charging is a process of charge transfer impacted by various factors, i.e., material surface characteristics, mechanical properties, processing parameters and environmental conditions. Consequently, this work aimed to assess how the charging behavior of capsules intended for inhalation might be influenced by environmental conditions. Capsules having different chemical compositions (gelatin and hydroxypropyl methylcellulose (HPMC)) and distinct inherent characteristics from manufacturing (thermally and cold-gelled) were exposed to various environmental conditions (11%, 22% and 51% RH). Their resulting properties were characterized and tribo-charging behavior was measured against stainless steel and PVC. It was observed that all capsule materials tended to charge to a higher extent when in contact with PVC. The tribo-charging of the thermally gelled HPMC capsules (Vcaps® Plus) was more similar to the gelatin capsules (Quali-G™-I) than to their HPMC cold-gelled counterparts (Quali-V®-I). The sorption of water by the capsules at different relative humidities notably impacted their properties and tribo-charging behavior. Different interactions between the tested materials and water molecules were identified and are proposed to be the driver of distinct charging behaviors. Finally, we showed that depending on the capsule types, distinct environmental conditions are necessary to mitigate charging and assure optimal behavior of the capsules.
Current Management and Outcome of Pregnancies in Women With Adrenal Insufficiency: Experience from a Multicenter Survey
Authors: Bothou Christina , Anand Gurpreet , Li Dingfeng , Kienitz Tina , Seejore Khyatisha , Simeoli Chiara , Ebbehoj Andreas , Ward Emma G , Paragliola Rosa Maria , Ferrigno Rosario , Badenhoop Klaus , Bensing Sophie , Oksnes Marianne , Esposito Daniela , Bergthorsdottir Ragnhildur , Drake William , Wahlberg Jeanette , Reisch Nicole , Hahner Stefanie , Pearce Simon , Trainer Peter , Etzrodt-Walter Gwendolin , Thalmann Sébastien P , Sævik Åse B , Husebye Eystein , Isidori Andrea M , Falhammar Henrik , Meyer Gesine , Corsello Salvatore M , Pivonello Rosario , Murray Robert , Bancos Irina , Quinkler Marcus , Beuschlein Felix
Published: May 2020

Context

Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment.

Objective

Multicenter survey on current clinical approaches in managing AI during pregnancy.

Design

Retrospective anonymized data collection from 19 international centers from 2013 to 2019.

Setting and Patients

128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%).

Results

Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes.

Conclusions

This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.
Late-Night Salivary Cortisol in Healthy, Community-Dwelling Asian Indians Assessed by Second-Generation ECLIA
Authors: Prasad Nandini , Jabbar Puthiyaveettil Khadar , Jayakumari Chellamma , John Mathew , Haridasan Retheesh Kollerazhikathu , Surendran Nair Anish Thekkumkara , Gomez Ramesh , Das Darvin Vamadevan , Sreenath Ravindranath , George Geena Susan , Nair Abilash
Published: May 2020

Background

Late-night salivary cortisol (LNSC) is used as a screening test for Cushing syndrome (CS), but there is no community-derived normative data for the normal upper limit in the South Asian population. This study aimed to determine the upper limit of normal (97.5th percentile) for LNSC in an Asian Indian population using a commercially available second-generation electrochemiluminiscence immunoassay (ECLIA).

Methods

LNSC in apparently healthy community-dwelling individuals was assessed by multistage cluster sampling. Healthy individuals age 18 to 60 years from 8 urban and 8 rural clusters of Thiruvananthapuram district were studied. Thirty people from an approximate population of 1000 individuals from each cluster participated in the study. A saliva sample was collected between 11 PM and 12 midnight and analyzed using Roche COBAS-e-411 and ultrasensitive Cortisol II kits the next day.

Results

Cortisol values from 474 salivary samples were available for final analysis after exclusion of improperly collected samples. The 97.5th percentile of the LNSC concentrations was 0.25 μg/dL (6.89 nmol/L) (90% CI, 0.23-0.27 μg/dL; ie, 6.34-7.45 nmol/L). In postmenopausal women, median LNSC was significantly higher but the 90% CI for the upper limit of their LNSC (0.28μg/dL or 7.72 nmol/L) overlapped with that of premenopausal women.

Conclusions

This study establishes the normal value of LNSC estimated by second-generation ECLIA in healthy community-dwelling Asian Indian individuals for the first time. Salivary cortisol at 11 pm to 12 am is less than 0.25μg/dL (6.89 nmol/L) in the general Asian Indian population. Menopause causes a significant increase in LNSC and may lead to overdiagnosis of CS if not interpreted carefully.
Growth and Adult Height in Girls With Turner Syndrome Following IGF-1 Titrated Growth Hormone Treatment
Authors: Cleemann Wang Amanda , Hagen Casper P , Nedaeifard Leila , Juul Anders , Jensen Rikke Beck
Published: May 2020

Context

Girls with Turner syndrome (TS) suffer linear growth failure, and TS is a registered indication for growth hormone (GH) treatment. GH is classically dosed according to body weight, and serum insulin-like growth factor-1 (IGF-1) concentrations are recommended to be kept within references according to international guidelines.

Objective

To assess the effect of long-term GH treatment in girls with TS following GH dosing by IGF-1 titration.

Design and setting

A retrospective, real-world evidence, observational study consisting of data collected in a single tertiary center from 1991 to 2018.

Patients

A cohort of 63 girls with TS treated with GH by IGF-1 titration with a median duration of 6.7 years (interquartile range [IQR]: 3.4-9.7 years).

Main outcome measures

Longitudinal measurements of height, IGF-1, and adult height (AH) following GH treatment were evaluated and compared between the different karyotypes (45,X, 45,X/46,XX, or miscellaneous).

Results

Using GH dose titration according to IGF-1, only 6% of girls with TS had supranormal IGF-1 levels. Median dose was 33 µg/kg/day (IQR: 28-39 µg/kg/day) with no difference between the karyotype groups. AH was reached for 73% who attained a median AH of 1.25 standard deviation score (SDS) for age specific TS references (IQR: 0.64-1.50 SDS), and a median gain in height (ΔHSDS: AH SDS minus baseline height SDS of TS references) of 0.50 SDS, equal to 3.2 cm (SD 7.68) for all karyotypes.

Conclusion

Our real-world evidence study suggested that titration of GH dose to keep IGF-1 levels within the normal range resulted in a lower AH gain than in studies where a fixed dose was used.
Dapagliflozin Does Not Directly Affect Human α or β Cells
Authors: Dai Chunhua , Walker John T , Shostak Alena , Bouchi Yasir , Poffenberger Greg , Hart Nathaniel J , Jacobson David A , Calcutt M Wade , Bottino Rita , Greiner Dale L , Shultz Leonard D , McGuinness Owen P , Dean E Danielle , Powers Alvin C
Published: May 2020

Selective inhibitors of sodium glucose cotransporter-2 (SGLT2) are widely used for the treatment of type 2 diabetes and act primarily to lower blood glucose by preventing glucose reabsorption in the kidney. However, it is controversial whether these agents also act on the pancreatic islet, specifically the α cell, to increase glucagon secretion. To determine the effects of SGLT2 on human islets, we analyzed SGLT2 expression and hormone secretion by human islets treated with the SGLT2 inhibitor dapagliflozin (DAPA) in vitro and in vivo. Compared to the human kidney, SLC5A2 transcript expression was 1600-fold lower in human islets and SGLT2 protein was not detected. In vitro, DAPA treatment had no effect on glucagon or insulin secretion by human islets at either high or low glucose concentrations. In mice bearing transplanted human islets, 1 and 4 weeks of DAPA treatment did not alter fasting blood glucose, human insulin, and total glucagon levels. Upon glucose stimulation, DAPA treatment led to lower blood glucose levels and proportionally lower human insulin levels, irrespective of treatment duration. In contrast, after glucose stimulation, total glucagon was increased after 1 week of DAPA treatment but normalized after 4 weeks of treatment. Furthermore, the human islet grafts showed no effects of DAPA treatment on hormone content, endocrine cell proliferation or apoptosis, or amyloid deposition. These data indicate that DAPA does not directly affect the human pancreatic islet, but rather suggest an indirect effect where lower blood glucose leads to reduced insulin secretion and a transient increase in glucagon secretion.
Impasse, Promise, and Impossible Community: Blanchot’s Community of Lovers and Kleist’sMichael Kohlhaas
Authors: Kuiken Kir
Published: May 2020

While “impasse” in politics implies deadlock or standstill, this essay examines how a counter-tradition, exemplified by Blanchot’s The Unavowable Community, treats impasse as the condition of possibility of a new form of community. Focusing on Blanchot’s conception of the “community of lovers,” the essay examines why Blanchot associates this with the events of May 1968. This association centers on the notion of an “impossible community” that challenges the very structure of the state as the realization of the community’s sovereignty. The essay then turns to Kleist, mentioned briefly in Blanchot’s treatise, as a paradigmatic case of the literary dimension of impossible community. Focusing on Kleist’s novella Michael Kohlhaas, the essay argues that the novella articulates the episodic and insurrectional element of Blanchot’s conception of community. Rather than understand the titular character’s revolt in terms of his fanatical adherence to the universality of law, the essay argues that Kohlhaas’s insurrection is predicated on the death of his wife, Lisbeth, whose post-mortem appearance in the novella introduces a promise that is structurally prior to the state’s constitution. This promise transforms impasse into enactment, impossibility into actuality.
Impasse? What Impasse?
Authors: Schey Taylor
Published: May 2020

Theories of historical and political change often rely on the idea of a breaking point at which radical action becomes a necessity. Theories of impasse—whether historical, political, or linguistic in focus—respond more or less directly to the assumptions behind this idea. This essay queries these assumptions. Opening with a discussion of how the concept of “the intolerable” features in the work of radical thinkers, the first section examines Lauren Berlant’s project in Cruel Optimism and explores her notion of “the impasse of the present.” The second section then turns to the work of Paul de Man, who, from Allegories of Reading on, develops a complementary theory of the impasse of the present that grows out of his theory of rhetorical reading. Although Berlant and de Man are each preoccupied in different ways with the idea of impasse, both ultimately demonstrate that impasse is best understood as an impossibility. Through readings of KC Green’s webcomics “On Fire” (best known as the source text of the “This is Fine” meme) and “This is Not Fine,” the essay illustrates and considers the broader implications of this impossibility.
Passing Impasse
Authors: François Anne-Lise
Published: May 2020

From Carolyn Merchant to Theodor Adorno, historians and critics of capitalist modernity have described its expansion as the story of the lifting of traditional taboos, or inversely as the laying down of a ban on taboo itself such that nothing is to remain off-limits or untouched. Yet, despite the absence of an answering authority to lay down the law and cry “halt,” and perhaps because of it, environmental harm continues to be imagined through the figure of trespass and in terms of an invisible line past which human activity, otherwise compelled by capitalism to limitless accumulation, must not go. At the same time, the more fungible the differences between ecological spheres, the more rigid the enforcement of state and private property lines, so that the discourse of trespass whereby one might hope to prosecute environmental crime in fact criminalizes once permitted commoning practices. This essay seeks to thread a way out of this impasse by turning to passages from John Clare, Rainer Maria Rilke, Charles Baudelaire, and William Wordsworth that map human and animal passing onto seasonal passage and mime the different levels and seasonal periods of permeability and impermeability found in ecological relations. Rather than accept the strict dichotomies of the logic of enclosure, the essay explores how these poets enact and theorize modes of passing in order to renew attention to temporary and seasonally determined forms of impasse and passage.