bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvements in functional and cognitive status following short-term pulmonary rehabilitation in COPD lung transplant recipients: a pilot study
Authors: Andrianopoulos Vasileios , Gloeckl Rainer , Boensch Martina , Hoster Katharina , Schneeberger Tessa , Jarosch Inga , Koczulla Rembert A. , Kenn Klaus
Published: September 2019

Background

Pulmonary rehabilitation (PR) following lung transplantation (LTx) is considered part of the optimal treatment in chronic obstructive pulmonary disease (COPD) for favourable post-operative outcomes. We investigated the effects of a PR intervention in the post-transplant phase with regard to lung function, exercise responses and cognitive function in COPD LTx recipients.

Methods

24 COPD LTx recipients (mean±sdforced expiratory volume in 1 s 75±22% predicted) were assigned to a comprehensive 3-week inpatient PR programme. Changes from PR admission to discharge in lung function variables, 6-min walk test-derived outcomes and cognitive function were assessed and examined for several factors. The magnitude of changes was interpreted by effect size (ES).

Results

In response to the PR intervention, LTx recipients had improved lung function with regard to diffusing capacity of the lung for carbon monoxide (+4.3%; p=0.012) and static hyperinflation (residual volume/total lung capacity −2.3%; p=0.017), increased exercise capacity (6-min walk test +86 m; p<0.001), and had small to large improvements (ES range 0.23–1.00; all p≤0.34) in 50% of the administered cognitive tests. Learning skills and memory ability presented the greatest benefits (ES composite scores 0.62 and 0.31, respectively), which remained similar after stratification by single or bilateral LTx and sex.

Conclusions

PR is an effective treatment for LTx recipients in the post-transplant phase, improving lung function, exercise responses, and domains of cognitive function of learning, memory and psychomotor speed. PR may facilitate the course of post-operative treatment and should be recommended in LTx.
Interleukin-6 inhibition in the management of non-infectious uveitis and beyond
Authors: Karkhur Samendra , Hasanreisoglu Murat , Vigil Erin , Halim Muhammad Sohail , Hassan Muhammad , Plaza Carlos , Nguyen Nam V. , Afridi Rubbia , Tran Anh T. , Do Diana V. , Sepah Yasir J. , Nguyen Quan Dong
Published: September 2019

Background

Uveitis consists of a spectrum of inflammatory disorders characterized by ocular inflammation. The underlying pathophysiology consists of a complex interplay of various inflammatory pathways. Interleukin 6 is an important mediator of inflammation in uveitis and constitutes focus of research toward development of newer biological therapies in the management of non-infectious uveitis.

Main body

Pan-blockade of the inflammatory pathways with steroids is generally the first step in the management of acute non-infectious uveitis. However, long-term therapy with steroids is associated with systemic and ocular side effects, thereby necessitating the need for development of steroid sparing agents. IL-6 is a cytokine produced by various immune cells, in response to molecular patterns and affects multiple inflammatory cells. In particular, IL-6 is involved in differentiation of CD-4 cells into Th-17 cells that have been shown to play a significant role in various immune-mediated diseases such as uveitis. This broad-spectrum immunomodulatory activity makes IL-6 an excellent target for immunomodulatory therapy. Tocilizumab was the first IL-6 inhibitor to demonstrate efficacy in humans. It inhibits IL-6 from binding to both membrane-bound and soluble receptor and can be administered via intravenous (IV) and subcutaneous (SC) routes. It has been FDA approved for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Following the approval in systemic diseases, its efficacy was demonstrated in various uveitis studies including a phase 2 clinical trial (STOP-Uveitis). Overall, tocilizumab has shown a good safety profile with the risk of malignancy consistent with that expected in patients with rheumatoid arthritis. However, tocilizumab therapy has been shown to increase the risk for gastrointestinal perforation and dose-dependent neutropenia. Following the success of tocilizumab, several other agents targeting the IL-6 pathway are in the pipeline. These include sirukumab, siltuximab, olokizumab, clazakizumab, and EBI-031 which target IL-6; Sarilumab and ALX-0061 act on the IL-6 receptor.

Conclusion

Studies have shown that IL-6 inhibitors can be effective in the management of NIU. In addition, the levels of IL-6 are elevated in other ocular vascular diseases such as retinal vein occlusion and diabetic macular edema. The roles of IL-6 inhibition may be broadened in the future to include the management of retinal vascular diseases and non-uveitic macular edema.
HH-suite3 for fast remote homology detection and deep protein annotation
Authors: Steinegger Martin , Meier Markus , Mirdita Milot , Vöhringer Harald , Haunsberger Stephan J. , Söding Johannes
Published: September 2019

Background

HH-suite is a widely used open source software suite for sensitive sequence similarity searches and protein fold recognition. It is based on pairwise alignment of profile Hidden Markov models (HMMs), which represent multiple sequence alignments of homologous proteins.

Results

We developed a single-instruction multiple-data (SIMD) vectorized implementation of the Viterbi algorithm for profile HMM alignment and introduced various other speed-ups. These accelerated the search methods HHsearch by a factor 4 and HHblits by a factor 2 over the previous version 2.0.16. HHblits3 is ∼10× faster than PSI-BLAST and ∼20× faster than HMMER3. Jobs to perform HHsearch and HHblits searches with many query profile HMMs can be parallelized over cores and over cluster servers using OpenMP and message passing interface (MPI). The free, open-source, GPLv3-licensed software is available at https://github.com/soedinglab/hh-suite.

Conclusion

The added functionalities and increased speed of HHsearch and HHblits should facilitate their use in large-scale protein structure and function prediction, e.g. in metagenomics and genomics projects.
Preferential activation of small cutaneous fibers through small pin electrode also depends on the shape of a long duration electrical current
Authors: Hugosdottir Rosa , Mørch Carsten Dahl , Andersen Ole Kæseler , Helgason Thordur , Arendt-Nielsen Lars
Published: September 2019

Background

Electrical stimulation is widely used in experimental pain research but it lacks selectivity towards small nociceptive fibers. When using standard surface patch electrodes and rectangular pulses, large fibers are activated at a lower threshold than small fibers. Pin electrodes have been designed for overcoming this problem by providing a higher current density in the upper epidermis where the small nociceptive fibers mainly terminate. At perception threshold level, pin electrode stimuli are rather selectively activating small nerve fibers and are perceived as painful, but for high current intensity, which is usually needed to evoke sufficient pain levels, large fibers are likely co-activated. Long duration current has been shown to elevate the threshold of large fibers by the mechanism of accommodation. However, it remains unclear whether the mechanism of accommodation in large fibers can be utilized to activate small fibers even more selectively by combining pin electrode stimulation with a long duration pulse.

Results

In this study, perception thresholds were determined for a patch- and a pin electrode for different pulse shapes of long duration. The perception threshold ratio between the two different electrodes was calculated to estimate the ability of the pulse shapes to preferentially activate small fibers. The perception threshold ratios were compared between stimulation pulses of 5- and 50 ms durations and shapes of: exponential increase, linear increase, bounded exponential, and rectangular. Qualitative pain perception was evaluated for all pulse shapes delivered at 10 times perception threshold. The results showed a higher perception threshold ratio for long duration 50 ms pulses than for 5 ms pulses. The highest perception threshold ratio was found for the 50 ms, bounded exponential pulse shape. Results furthermore revealed different strength-duration relation between the bounded exponential- and rectangular pulse shapes. Pin electrode stimulation at high intensity was mainly described as “stabbing”, “shooting”, and “sharp”.

Conclusion

These results indicate that long duration pulses with a bounded exponential increase preferentially activate the small nociceptive fibers with a pin electrode and concurrently cause elevated threshold of large non-nociceptive fibers with patch electrodes.
Does Pentaerytrithyltetranitrate reduce fetal growth restriction in pregnancies complicated by uterine mal-perfusion? Study protocol of the PETN-study: a randomized controlled multicenter-trial
Authors:   for the PETN Study Group, Groten T. , Lehmann T. , Schleußner E.
Published: September 2019

Background

Affecting approximately 10% of pregnancies, fetal growth restriction (FGR), is the most important cause of perinatal mortality and morbidity. Impaired placental function and consequent mal-perfusion of the placenta is the leading cause of FGR. Although, screening for placental insufficiency based on uterine artery Doppler measurement is well established, there is no treatment option for pregnancies threatened by FGR. The organic nitrate pentaerithrityl tetranitrate (PETN) is widely used for the treatment of cardiovascular disease and has been shown to have protective effects on human endothelial cells. In a randomized placebo controlled pilot-study our group could demonstrate a risk reduction of 39% for the development of FGR, and FGR or death, by administering PETN to patients with impaired uterine artery Doppler at mid gestation. To confirm these results a prospective randomized placebo controlled double-blinded multicentre trial was now initiated.

Method

The trial has been initiated in 14 centres in Germany. Inclusion criteria are abnormal uterine artery Doppler, defined by mean PI > 1.6, at 190 to 226 weeks of gestation in singleton pregnancies. Included patients will be monitored in 4-week intervals. Primary outcome measures are development of FGR (birth weight < 10th percentile), severe FGR (birth weight < 3rd centile) and perinatal death. Placental abruption, birth weight below the 3rd, 5th and 10th centile, development of FGR requiring delivery before 34 weeks` gestation, neonatal intensive care unit admission, and spontaneous preterm delivery < 34 weeks` and 37 weeks` gestation will be assessed as secondary endpoints. Patient enrolment was started in August 2017. Results are expected in 2020.

Discussion

During the past decade therapeutic agents with possible perfusion optimizing potential have been evaluated in clinical trials to treat FGR. Meta-analysis and sub-analysis of trials targeting preeclampsia revealed ASS to have a potential in reducing FGR. Phosphodiesterase-type-5 inhibitors have recently been tested in a worldwide RCT for therapy of established FGR, failing to show an effect on neonatal outcome. The ongoing multicenter trial will, by confirming our previous results, finally provide a therapeutic option in cases at risk for FGR.

Trial registration

DRKS00011374 registered at September 29th, 2017 and NCT03669185, registered September 13th, 2018.
Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice
Authors: Shekhar Tanmay M. , Burvenich Ingrid J. G. , Harris Michael A. , Rigopoulos Angela , Zanker Damien , Spurling Alex , Parker Belinda S. , Walkley Carl R. , Scott Andrew M. , Hawkins Christine J.
Published: September 2019

Background

Current therapies fail to cure over a third of osteosarcoma patients and around three quarters of those with metastatic disease. “Smac mimetics” (also known as “IAP antagonists”) are a new class of anti-cancer agents. Previous work revealed that cells from murine osteosarcomas were efficiently sensitized by physiologically achievable concentrations of some Smac mimetics (including GDC-0152 and LCL161) to killing by the inflammatory cytokine TNFα in vitro, but survived exposure to Smac mimetics as sole agents.

Methods

Nude mice were subcutaneously or intramuscularly implanted with luciferase-expressing murine 1029H or human KRIB osteosarcoma cells. The impacts of treatment with GDC-0152, LCL161 and/or doxorubicin were assessed by caliper measurements, bioluminescence,18FDG-PET and MRI imaging, and by weighing resected tumors at the experimental endpoint. Metastatic burden was examined by quantitative PCR, through amplification of a region of the luciferase gene from lung DNA. ATP levels in treated and untreated osteosarcoma cells were compared to assess in vitro sensitivity. Immunophenotyping of cells within treated and untreated tumors was performed by flow cytometry, and TNFα levels in blood and tumors were measured using cytokine bead arrays.

Results

Treatment with GDC-0152 or LCL161 suppressed the growth of subcutaneously or intramuscularly implanted osteosarcomas. In both models, co-treatment with doxorubicin and Smac mimetics impeded average osteosarcoma growth to a greater extent than either drug alone, although these differences were not statistically significant. Co-treatments were also more toxic. Co-treatment with LCL161 and doxorubicin was particularly effective in the KRIB intramuscular model, impeding primary tumor growth and delaying or preventing metastasis. Although the Smac mimetics were effective in vivo, in vitro they only efficiently killed osteosarcoma cells when TNFα was supplied. Implanted tumors contained high levels of TNFα, produced by infiltrating immune cells. Spontaneous osteosarcomas that arose in genetically-engineered immunocompetent mice also contained abundant TNFα.

Conclusions

These data imply that Smac mimetics can cooperate with TNFα secreted by tumor-associated immune cells to kill osteosarcoma cells in vivo. Smac mimetics may therefore benefit osteosarcoma patients whose tumors contain Smac mimetic-responsive cancer cells and TNFα-producing infiltrating cells.
Effect of play-based family-centered psychomotor/psychosocial stimulation on the development of severely acutely malnourished children under six in a low-income setting: a randomized controlled trial
Authors: Abessa Teklu Gemechu , Worku Berhanu Nigussie , Wondafrash Mekitie , Girma Tsinuel , Valy Johan , Lemmens Johan , Bruckers Liesbeth , Kolsteren Patrick , Granitzer Marita
Published: September 2019

Background

The World Health Organization (WHO) recommends incorporating psychosocial stimulation into the management of severe acute malnutrition (SAM). However, there is little evidence about the effectiveness of these interventions for SAM children, particularly when serious food shortages and lack of a balanced diet prevail. The objective of this study was to examine whether family-based psychomotor/psychosocial stimulation in a low-income setting improves the development, linear growth, and nutritional outcomes in children with SAM.

Method

Children with SAM (N = 339) admitted for treatment to the Jimma University Specialized Hospital, Ethiopia, were randomized to a control (n = 170) or intervention (n = 169) group. Both groups received routine medical care and nutritional treatment at the hospital. The intervention group additionally received play-based psychomotor/psychosocial stimulation during their hospital stay, and at home for 6 months after being discharged from hospital.

The fine motor (FM) and gross motor (GM) functions, language (LA) and personal-social (PS) skills of the children were assessed using adapted Denver II, the social-emotional (SE) behavior was assessed using adapted Ages and Stages Questionnaires: Social-Emotional, and the linear growth and nutritional status were determined through anthropometric assessments. All outcomes were assessed before the intervention, upon discharge from hospital, and 6 months after discharge (as end-line). The overtime changes of these outcomes measured in both groups were compared using Generalized Estimating Equations.

Results

The intervention group improved significantly on GM during hospital follow-up by 0.88 points (p < 0.001, effect size = 0.26 SD), and on FM functions during the home follow-up by 1.09 points (p = 0.001, effect size = 0.22 SD). Both young and older children benefited similarly from the treatment. The intervention did not contribute significantly to linear growth and nutritional outcomes.

Conclusion

Psychomotor/psychosocial stimulation of SAM children enhances improvement in gross motor functions when combined with standard nutrient-rich diets, but it can enhance the fine motor functions even when such standard dietary care is not available.

Trial registration

The trial was retrospectively registered on 30 January 2017 at the US National Institute of Health (ClinicalTrials.gov) #NCT03036176.
Laparoscopic vs open colorectal cancer surgery in elderly patients: short- and long-term outcomes and predictors for overall and disease-free survival
Authors: Zhou Sicheng , Wang Xuewei , Zhao Chuanduo , Liu Qian , Zhou Haitao , Zheng Zhaoxu , Zhou Zhixiang , Wang Xishan , Liang Jianwei
Published: September 2019

Background

Colorectal cancer is common in elderly patients. Laparoscopy is widely used to approach this kind of disease. This study was to examine short-term outcomes and long-term survival for laparoscopic and open surgery in elderly patients with colorectal cancer.

Methods

From January 2007 to December 2018, patients with colorectal cancer older than 80 operated at China National Cancer Center were included in the study. Propensity score matching (PSM) was used to minimize the adverse effects. The clinical data between open and laparoscopic surgery was compared, and the effect of factors on overall survival (OS) and disease-free survival (DFS) was analyzed by Cox proportional hazard model.

Results

Ninety-three pairs were selected after PSM. Patients in laparoscopic group had less intraoperative blood loss, postoperative complications, time to first flatus, time to oral feeding, postoperative hospital stay, and higher retrieved lymph node (P < 0.05). The OS and DFS rates were similar (P > 0.05), besides the CEA level, III/IV stage, and perineural invasion were independent predictors of survival (P < 0.05).

Conclusion

In elderly patients with colorectal cancer, laparoscopic surgery had better short-term outcomes than open surgery. CEA level, III/IV stage, and perineural invasion were reliable predictors for OS and DFS.
Patient-reported outcomes in randomised clinical trials of bladder cancer: an updated systematic review
Authors: Van Hemelrijck Mieke , Sparano Francesco , Josephs Debra , Sprangers Mirjam , Cottone Francesco , Efficace Fabio
Published: September 2019

Background

Despite international recommendations of including patient-reported outcomes (PROs) in randomised clinical trials (RCTs), a 2014 review concluded that few RCTs of bladder cancer (BC) report PRO as an outcome. We therefore aimed to update the 2014 review to synthesise current evidence-based knowledge of PROs from RCTs in BC. A secondary objective was to examine whether quality of PRO reporting has improved over time and to provide evidence-based recommendations for future studies in this area.

Methods

We conducted a systematic literature search using PubMed/Medline, from April 2014 until June 2018. We included the RCTs identified in the previous review as well as newly published RCTs. Studies were evaluated using a predefined electronic-data extraction form that included information on basic trial demographics, clinical and PRO characteristics and standards of PRO reporting based on recommendation from the International Society of Quality of Life Research.

Results

Since April 2014 only eight new RCTs for BC included PROs as a secondary outcome. In terms of methodology, only the proportion of RCTs documenting the extent of missing PRO data (75% vs 11.1%, p = 0.03) and the identification of PROs in trial protocols (50% vs 0%, p = 0.015) improved. Statistical approaches for dealing with missing data were not reported in most new studies (75%).

Conclusion

Little improvement into the uptake and assessment of PRO as an outcome in RCTs for BC has been made during recent years. Given the increase in (immunotherapy) drug trials with a potential for severe adverse events, there is urgent need to adopt the recommendations and standards available for PRO use in bladder cancer RCTs.
The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma
Authors: Hii Ling-Wei , Lim Swee-Hua Erin , Leong Chee-Onn , Chin Swee-Yee , Tan Ngai-Paing , Lai Kok-Song , Mai Chun-Wai
Published: September 2019

Background

Clinacanthus nutans extracts have been consumed by the cancer patients with the hope that the extracts can kill cancers more effectively than conventional chemotherapies. Our previous study reported its anti-inflammatory effects were caused by inhibiting Toll-like Receptor-4 (TLR-4) activation. However, we are unsure of its anticancer effect, and its interaction with existing chemotherapy.

Methods

We investigated the anti-proliferative efficacy of polar leaf extracts (LP), non-polar leaf extracts (LN), polar stem extract (SP) and non-polar stem extracts (SN) in human breast, colorectal, lung, endometrial, nasopharyngeal, and pancreatic cancer cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT assay. The most potent extracts was tested along with gemcitabine using our established drug combination analysis. The effect of the combinatory treatment in apoptosis were quantified using enzyme-linked immunosorbent assay (ELISA), Annexin V assay, antibody array and immunoblotting. Statistical significance was analysed using one-way analysis of variance (ANOVA) and post hoc Dunnett’s test. A p-value of less than 0.05 (p < 0.05) was considered statistical significance.

Results

All extracts tested were not able to induce potent anti-proliferative effects. However, it was found that pancreatic ductal adenocarcinoma, PDAC (AsPC1, BxPC3 and SW1990) were the cell lines most sensitive cell lines to SN extracts. This is the first report of C. nutans SN extracts acting in synergy with gemcitabine, the first line chemotherapy for pancreatic cancer, as compared to conventional monotherapy. In the presence of SN extracts, we can reduce the dose of gemcitabine 2.38–5.28 folds but still maintain the effects of gemcitabine in PDAC. SN extracts potentiated the killing of gemcitabine in PDAC by apoptosis. Bax was upregulated while bcl-2, cIAP-2, and XIAP levels were downregulated in SW1990 and BxPC3 cells treated with gemcitabine and SN extracts. The synergism was independent of TLR-4 expression in pancreatic cancer cells.

Conclusion

These results provide strong evidence of C. nutans extracts being inefficacious as monotherapy for cancer. Hence, it should not be used as a total substitution for any chemotherapy agents. However, SN extracts may synergise with gemcitabine in the anti-tumor mechanism.
The implementation of the coaching on lifestyle (CooL) intervention: lessons learnt
Authors: van Rinsum Celeste , Gerards Sanne , Rutten Geert , Johannesma Madelon , van de Goor Ien , Kremers Stef
Published: September 2019

Background

Combined lifestyle interventions (CLIs) are designed to help people who are overweight or obese maintain a healthy new lifestyle. The CooL intervention is a CLI in the Netherlands, in which lifestyle coaches counsel adults and children (and/or their parents) who are obese or at high risk of obesity to achieve a sustained healthier lifestyle. The intervention consists of coaching on lifestyle in group and individual sessions, addressing the topics of physical activity, dietary behaviours, sleep, stress management and behavioural change. The aim of this study was to evaluate the implementation process of the Coaching on Lifestyle (CooL) intervention and its facilitating and impeding factors.

Methods

Mixed methods were used in this action-oriented study. Both quantitative (number of referrals, attendance lists of participants and questionnaires) and qualitative (group and individual interviews, observations, minutes and open questions) data were collected among participants, lifestyle coaches, project group members and other stakeholders. The Consolidated Framework for Implementation Research was used to analyse the data.

Results

CooL was evaluated by stakeholders and participants as an accessible and useful programme, because of its design and content and the lifestyle coaches’ approach. However, stakeholders indicated that the lifestyle coaches need to become more familiar in the health care network and public sectors in the Netherlands. Lifestyle coaching is a novel profession and the added value of the lifestyle coach is not always acknowledged by all health care providers. Lifestyle coaches play a crucial role in ensuring the impact of CooL by actively networking, using clear communication materials and creating stakeholders’ support and understanding.

Conclusion

The implementation process needs to be strengthened in terms of creating support for and providing clear information about lifestyle coaching. The CooL intervention was implemented in multiple regions, thanks to the efforts of many stakeholders. Lifestyle coaches should engage in networking activities and entrepreneurship to boost the implementation process. It takes considerable time for a lifestyle coach to become fully incorporated in primary care.

Trial registration

NTR6208; date registered: 13–01-2017; retrospectively registered; Netherlands Trial Register.
Re-energising the way we manage change in healthcare: the case for soft systems methodology and its application to evidence-based practice
Authors: Augustsson Hanna , Churruca Kate , Braithwaite Jeffrey
Published: September 2019

Background

Updating, improving and spreading the evidence base for healthcare practices has proven to be a challenge of considerable magnitude – a wicked, multi-dimensional problem. There are many interlinked factors which determine how, why and whether any particular implementation effort or intervention succeeds. Soft Systems Methodology (SSM), strongly grounded in systems ideas and complexity science, offers a structured, yet flexible process for dealing with situations that are perceived as problematical and in need of improvement. The aim of this paper is to propose the use of SSM for managing change in healthcare by way of addressing some of the complexities. The aim is further to illustrate examples of how SSM has been used in healthcare and discuss the features of the methodology that we believe can be harnessed to improve healthcare.

Discussion

SSM is particularly suited for tackling real world problems that are difficult to define and where stakeholders may have divergent views on the situation and the objectives of change. SSM engages stakeholders in a learning cycle including: finding out about the problematical situation, i.e. the context in which the problem exists, by developing a rich picture of the situation; defining it by developing conceptual models and comparing these with the real world; taking action to improve it by deciding on desirable and feasible improvements; and implementing these in an iterative manner. Although SSM has been widely used in other sectors, it has not been extensively used in healthcare. We make the case for applying SSM to implementation and improvement endeavours in healthcare using the example of getting clinicians at the hospital level to use evidence-based guidelines.

Conclusion

Applying SSM means taking account of the multi-dimensional nature of care settings, and dealing with entrenched and unique contexts, cultures and socio-political ecosystems – precisely those that manifest in healthcare. There are gains to be made in appreciating complexity and facilitating contextualization of interventions, and by approaching improvements in an iterative learning cycle.
Performance of family planning clinics in conducting recommended HIV counseling and testing in Mombasa County, Kenya: a cross-sectional study
Authors: Eastment McKenna C. , Wanje George , Richardson Barbra A. , Nassir Faiza , Mwaringa Emily , Barnabas Ruanne V. , Sherr Kenneth , Mandaliya Kishorchandra , Jaoko Walter , McClelland R. Scott
Published: September 2019

Background

A high proportion of African women utilize family planning (FP) services. Accordingly, incorporating HIV testing into FP services may strategically target the first WHO 90–90-90 goal of 90% of people living with HIV knowing their status.

Methods

The objective of this analysis was to determine the proportion of new FP clients counseled and tested for HIV, as well as correlates of HIV testing, in a random sample of 58 FP clinics in Mombasa County, Kenya. Structured interviews of FP clinic managers collected data on characteristics of FP clinics and staff. Study staff performed a 3-month review of FP registers, summarizing new client HIV testing and counseling (HTC). Because overall rates of HTC were quite low, a binary variable was created comparing clinics performing any HIV counseling and/or testing to clinics performing none. Generalized linear models were used to calculate prevalence ratios (PR) and identify correlates of HTC. Factors associated with any HTC with a p-value < 0.10 in univariate analysis were included in a multivariate analysis.

Results

Of the 58 FP clinics, 26 (45%) performed any counseling for HIV testing, and 23 (40%) performed any HIV testing. Counseling for HIV testing was conducted for 815/4389 (19%) new clients, and HIV testing was performed for 420/4389 (10%). Clinics without trained HIV testing providers uniformly did not conduct HIV counseling and/or testing (0/12 [0%]), while 27/46 (59%) of clinics with ≥1 provider performed some HTC (p < 0.001). In the subset of 46 clinics with ≥1 trained HIV testing provider, correlates of performing HTC included being a public versus non-public clinic (PR 1.70 95%CI 1.01–2.88), and having an HIV comprehensive care center (CCC) onsite (PR 2.05, 95%CI 1.04–4.06).

Conclusion

Trained HIV testing providers are crucial for FP clinics to perform any HTC. Approaches are needed to increase routine HTC in FP clinics including staffing changes and/or linkages with other testing services (in standalone VCT services or lab facilities) in order to improve the implementation of existing national guidelines. A future cluster randomized trial is planned to test an implementation strategy, the Systems Analysis and Improvement Approach (SAIA) to increase HTC in FP clinics.
Quantitative structure–activity relationship to predict the anti-malarial activity in a set of new imidazolopiperazines based on artificial neural networks
Authors: Yousefinejad Saeed , Mahboubifar Marjan , Eskandari Rayhaneh
Published: September 2019

Background

After years of efforts on the control of malaria, it remains as a most deadly infectious disease. A major problem for the available anti-malarial drugs is the occurrence of drug resistance in Plasmodium. Developing of new compounds or modification of existing anti-malarial drugs is an effective approach to face this challenge. Quantitative structure activity relationship (QSAR) modelling plays an important role in design and modification of anti-malarial compounds by estimation of the activity of the compounds.

Methods

In this research, the QSAR study was done on anti-malarial activity of 33 imidazolopiperazine compounds based on artificial neural networks (ANN). The structural descriptors of imidazolopiperazine molecules was used as the independents variables and their activity against 3D7 and W2 strains was used as the dependent variables. During modelling process, 70% of compound was used as the training and two 15% of imidazolopiperazines were used as the validation and external test sets. In this work, stepwise multiple linear regression was applied as the valuable selection and ANN with Levenberg–Marquardt algorithm was utilized as an efficient non-linear approach to correlate between structural information of molecules and their anti-malarial activity.

Results

The sufficiency of the suggested method to estimate the anti-malarial activity of imidazolopiperazine compounds at two 3D7 and W2 strains was demonstrated using statistical parameters, such as correlation coefficient (R2), mean square error (MSE). For instance R2train = 0.947, R2val = 0.959, R2test = 0.920 shows the potential of the suggested model for the prediction of 3D7 activity. Different statistical approaches such as and applicability domain (AD) and y-scrambling was also showed the validity of models.

Conclusion

QSAR can be an efficient way to virtual screening the molecules to design more efficient compounds with activity against malaria (3D7 and W2 strains). Imidazolopiperazines can be good candidates and change in the structure and functional groups can be done intelligently using QSAR approach to rich more efficient compounds with decreasing trial–error runs during synthesis.
Relationship between S100A4 protein expression and pre-operative serum CA19.9 levels in pancreatic carcinoma and its prognostic significance
Authors: Jia Fuxin , Liu Mengmeng , Li Xiao , Zhang Fen , Yue Shuqiang , Liu Jiangwei
Published: September 2019

Background

Pancreatic carcinoma (PC) is one of the most lethal malignancies, and its poor prognosis is strongly associated with invasion and metastasis. CA19.9 is considered to be the most sensitive serum marker for PC in clinical practice; however, the detection of CA19.9 in PC has a certain false positive and false negative rate. The expression of the calcium-binding protein S100A4 has been reported to be associated with poor prognosis in various cancers. This study aimed to investigate the relationship between S100A4 and CA19.9 and its prognostic significance in PC.

Methods

We performed immunohistochemical staining for S100A4 in formalin-fixed, paraffin-embedded blocks of 128 PC tissues. The levels of S100A4 expression and pre-operative serum CA19.9 were correlated with clinicopathological parameters. The possible correlation between S100A4 protein expression and pre-operative serum CA19.9 levels were evaluated using the chi-square test and Spearman correlation. Survival was assessed by Kaplan–Meier analysis together with a single variable or multivariate Cox analysis.

Results

A significant positive correlation between S100A4 expression and pre-operative serum CA19.9 level was observed in PC tissues (ρ= 0.202,P= 0.022). The co-expression of both proteins correlated significantly with tumor differentiation (ρ= − 0.280,P= 0.001), TNM stage (ρ= − 0.389,P= 0.000), and lymph node metastasis (ρ= 0.254,P= 0.008). Upregulation of S100A4 was identified as a significant, independent predictor of poor overall survival (P= 0.000). Moreover, higher serum CA19.9 levels (≥ 35 U/mL) were also recognized as an independent predictor of inferior overall survival (P= 0.001). Additionally, upregulation of S100A4 and higher pre-operative serum CA19.9 levels (≥ 35 U/mL) in patients with PC contributed to a significant decrease in overall survival (P= 0.000).

Conclusions

The expression levels of S100A4 in PC tissues were positively correlated with pre-operative serum CA19.9 levels. S100A4 expression and pre-operative serum CA19.9 levels were significant, independent prognostic factors for the overall survival of patients with PC. S100A4 expression/pre-operative serum CA19.9 levels may prove useful as dual prognostic biomarkers for PC. Analysis of CA19.9 in combination with S100A4 can better predict the prognosis of PC.
Effects of metformin and Exenatide on insulin resistance and AMPKα-SIRT1 molecular pathway in PCOS rats
Authors: Tao Xin , Cai Lisi , Chen Lei , Ge Shuqi , Deng Xuanying
Published: September 2019

Aims

This study was designed to evaluate the protective effects of AMPKα and SIRT1 on insulin resistance in PCOS rats, and to illuminate the underlying mechanisms.

Methods

An in vitro PCOS model was established by DHEA (6 mg/(100 g•d)), and the rats were randomly divided into the metformin group (MF group, n = 11), the exenatide group (EX group, n = 11), the PCOS group (n = 10), and the normal control group (NC group, n = 10). The MF group was administered MF 300 mg/(kg•d) daily. The EX group was subcutaneously injected EX 10μg/(kg•d) daily. After 4 weeks of continuous administration, fasting blood glucose and serum androgen, luteinizing hormone and other biochemical indicators were measured. Western and Real-time PCR were used to determine the expression of AMPKα and SIRT1 in the ovaries of each group.

Results

After 4 weeks of drug intervention, compared with untreated PCOS group, EX group and MF group had visibly decreased body weight (222.64 ± 16.57, 218.63 ± 13.18 vs 238.30 ± 12.26 g, P = 0.026), fasting blood glucose (7.71 ± 0.72, 8.17 ± 0.54 vs 8.68 ± 0.47 mmol/L, P < 0.01), HOMA-IR (8.26 ± 2.50, 7.44 ± 1.23 vs 12.66 ± 1.44, P < 0.01) and serum androgen (0.09 ± 0.03, 0.09 ± 0.03 vs 0.53 ± 0.41 ng/ml, P < 0.01) and the expressions of AMPKα and SIRT11 were increased progressively (P < 0.05).

Conclusions

Both metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPKα-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target.
Effective continuous acetone–butanol–ethanol production with full utilization of cassava by immobilized symbiotic TSH06
Authors: Lin Zhangnan , Liu Hongjuan , Wu Jing , Patakova Petra , Branska Barbora , Zhang Jianan
Published: September 2019

Background

Butanol production by fermentation has recently attracted increasingly more attention because of its mild reaction conditions and environmentally friendly properties. However, traditional feedstocks, such as corn, are food supplies for human beings and are expensive and not suitable for butanol production at a large scale. In this study, acetone, butanol, and ethanol (ABE) fermentation with non-pretreated cassava using a symbiotic TSH06 was investigated.

Results

In batch fermentation, the butanol concentration of 11.6 g/L was obtained with a productivity of 0.16 g/L/h, which was similar to that obtained from glucose system. A full utilization system of cassava was constructed to improve the fermentation performance, cassava flour was used as the substrate and cassava peel residue was used as the immobilization carrier. ABE fermentation with immobilized cells resulted in total ABE and butanol concentrations of 20 g/L and 13.3 g/L, which were 13.6% and 14.7% higher, respectively, than those of free cells. To further improve the solvent productivity, continuous fermentation was conducted with immobilized cells. In single-stage continuous fermentation, the concentrations of total ABE and butanol reached 9.3 g/L and 6.3 g/L with ABE and butanol productivities of 1.86 g/L/h and 1.26 g/L/h, respectively. In addition, both of the high product concentration and high solvent productivity were achieved in a three-stage continuous fermentation. The ABE productivity and concentration was 1.12 g/L/h and 16.8 g/L, respectively.

Conclusions

The results indicate that TSH06 could produce solvents from cassava effectively. This study shows that ABE fermentation with cassava as a substrate could be an efficient and economical method of butanol production.
ESR statement on portable ultrasound devices
Authors:   European Society of Radiology (ESR)
Published: September 2019

The use of portable ultrasound (US) devices has increased in recent years and the market has been flourishing. Portable US devices can be subdivided into three groups: laptop-associated devices, hand-carried US, and handheld US devices. Almost all companies we investigated offer at least one portable US device. Portable US can also be associated with the use of different US techniques such as colour Doppler US and pulse wave (PW)-Doppler. Laptop systems will also be available with contrast-enhanced US and high-end cardiac functionality.

Portable US devices are effective in the hands of experienced examiners. Imaging quality is predictably inferior to so-called high-end devices.

The present paper is focused on portable US devices and clinical applications describing their possible use in different organs and clinical settings, keeping in mind that patient safety must never be compromised. Hence, portable devices must undergo the same decontamination assessment and protocols as the standard equipment, especially smartphones and tablets.
Health risk assessment of potentially toxic elements via consumption of vegetables irrigated with polluted river water in Addis Ababa, Ethiopia
Authors: Aschale Minbale , Sileshi Yilma , Kelly-Quinn Mary
Published: September 2019

Background

Vegetables grown at contaminated sites can take up and accumulate toxic and potentially toxic elements at concentrations that are toxic to human health. The present study determined the levels of potentially toxic elements/PTEs in irrigation water, soil and vegetable samples grown along contaminated river and assessed the potential health risks to consumers.

Results

The average concentrations of Mn, Sr and Cr in the irrigation water were higher than the international guideline values. The levels of As, Cr, B and Ni in most of the farm soils were also found to be higher than the guideline values. Other PTEs, although not exceeding the recommended limits were relatively high in the soil and water samples. The study also revealed that the mean levels of Cr, Cd and Fe in most vegetables were higher than the maximum recommended limits. Swiss chard was maximally contaminated with PTEs followed by lettuce, cabbage, Ethiopian kale, carrot and potato. Hence, frequent consumption of lettuce and Swiss chard may cause serious health risks to consumers.

Conclusion

The levels of many elements were varied with location, suggesting localized inputs of the various contaminants related to industrial and other activities that generate wastewater.
Splits in students’ beliefs about learning classical and quantum physics
Authors: Dreyfus Benjamin W. , Hoehn Jessica R. , Elby Andrew , Finkelstein Noah D. , Gupta Ayush
Published: September 2019

Background

While there has been increasing recognition of the importance of attending to students’ views about what counts as knowing and learning a STEM field, surveys that measure these “epistemological” beliefs are often used in ways that implicitly assume the fields, e.g., “physics,” to be a single domain about which students might have sophisticated or naïve beliefs. We demonstrate this is not necessarily the case and argue for attending to possible differences in students’ epistemological beliefs across different sub-domains of physics. In modern physics and quantum mechanics courses for engineering and physics students, we administered a set of modified Colorado Learning Attitudes about Science Survey (CLASS) items. Each selected item was turned into two items, with the word “physics” changed to “classical physics” in one and “quantum physics” in the other.

Results

We found significant splits between students’ survey responses about classical vs. quantum physics on some items, both pre- and post-instruction. In classical physics, as compared to quantum physics, students were more likely to report the salience of real-world connections and the possibility of combining mathematical and conceptual reasoning during problem solving.

Conclusions

These findings suggest that attending to sub-domain specificity of students’ beliefs about physics can be fruitful and ought to influence our instructional choices.
Similar bacterial communities on healthy and injured skin of black tip reef sharks
Authors: Pogoreutz Claudia , Gore Mauvis A. , Perna Gabriela , Millar Catriona , Nestler Robert , Ormond Rupert F. , Clarke Christopher R. , Voolstra Christian R.
Published: September 2019

Background

Sharks are in severe global decline due to human exploitation. The additional concern of emerging diseases for this ancient group of fish, however, remains poorly understood. While wild-caught and captive sharks may be susceptible to bacterial and transmissible diseases, recent reports suggest that shark skin may harbor properties that prevent infection, such as a specialized ultrastructure or innate immune properties, possibly related to associated microbial assemblages. To assess whether bacterial community composition differs between visibly healthy and insulted (injured) shark skin, we compared bacterial assemblages of skin covering the gills and the back from 44 wild-caught black-tip reef sharks (Carcharhinus melanopterus) from the Amirante Islands (Seychelles) via 16S rRNA gene amplicon sequencing.

Results

Shark skin-associated bacterial communities were diverse (5971 bacterial taxa from 375 families) and dominated by three families of the phylum Proteobacteria typical of marine organisms and environments (Rhodobacteraceae, Alteromonadaceae, Halomonadaceae). Significant differences in bacterial community composition of skin were observed for sharks collected from different sites, but not between healthy or injured skin samples or skin type (gills vs. back). The core microbiome (defined as bacterial taxa present in ≥50% of all samples) consisted of 12 bacterial taxa, which are commonly observed in marine organisms, some of which may be associated with animal host health.

Conclusion

The conserved bacterial community composition of healthy and injured shark skin samples suggests absence of severe bacterial infections or substantial pathogen propagation upon skin insult. While a mild bacterial infection may have gone undetected, the overall conserved bacterial community implies that bacterial function(s) may be maintained in injured skin. At present, the contribution of bacteria, besides intrinsic animal host factors, to counter skin infection and support rapid wound healing in sharks are unknown. This represents clear knowledge gaps that should be addressed in future work, e.g. by screening for antimicrobial properties of skin-associated bacterial isolates.
Psychiatric disturbances in patients undergoing open-heart surgery
Authors: Younes Osama , Amer Reham , Fawzy Hosam , Shama Gamal
Published: September 2019

Background

Emotional and behavioral problems have been noted in a considerable number of patients after open-heart surgery. However, great discrepancy exists in the literature regarding the frequency and the course of psychiatric symptoms, cognitive performance, and quality of life among those patients. This prospective study was designed to assess the pre- and postoperative psychiatric profile, as well as the quality of life of patients undergoing open-heart surgery.

Methods

One hundred patients who were prepared for cardiac surgery and met our selection criteria were recruited in this study. Each patient was subjected to the Hospital Anxiety and Depression Scale, the Mini-Mental State Examination with selective subtests of Wechsler Adult intelligence scale, and the Short Form 36 questionnaire to assess psychiatric symptoms, cognitive performance, and quality of life respectively. Assessment was done for each of the evaluated items before surgery as well as at 1 week and 6 months postoperatively.

Results

The anxiety and depressive symptoms were significantly lower at 6 months postoperatively than preoperatively. The cognitive performance declined after 1 week, then improved significantly at the 6-month follow-up. The quality of life scale was significantly lower preoperatively than after surgery.

Conclusions

Anxiety and depressive symptoms, which occurred in substantial percentage of patients undergoing open-heart surgery, were gradually improved with time. Cognitive functions showed early deterioration with significant improvement at 6 months. Psychiatric problems had an adverse impact on patients’ quality of life which raised the importance of psychiatric consultation before and after cardiac surgeries to shorten recovery time.