bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation, migration and expectation: internationally qualified health practitioners in Australia—a qualitative study
Authors: Cooper Melissa , Rasmussen Philippa , Magarey Judy
Published: October 2020

Background

The global movement of internationally qualified health practitioners (IQHPs), seeking to live and work outside of their place of origin, is subject to considerable study and scrutiny. Extensive published material exists, from government enquiries and print news media articles to peer-reviewed papers, reporting on the views and impacts of migration and practitioner registration. Unsurprisingly much of the research focuses on the two largest groups of health professionals, international medical graduates (IMG) and internationally qualified nurses (IQN). This paper presents a unique case study examining the challenges and complexities of navigating the regulatory processes for skilled migration and practitioner registration in Australia.

Discussion

The study comprised a review and analysis of the current policy frameworks, standards and assessment models applied by regulators affecting skilled migration and registration of IQHPs. To target the triangulated themes of regulation, experience and expectations, a phenomenological component was also conducted with the mapping of shared experiences of four key participant groups comprising the following: assessors operationalising the current policies and processes governing skilled migration and registration, educators offering preparatory and training programs to IQHP, workforce agencies engaging with and recruiting IQHP and internationally qualified doctors, nurses and midwives. The study was informed by rich qualitative data extracted from twenty-eight in-depth semi-structured participant interviews. Key themes and points of intersection between participant experiences and the regulatory frameworks were identified using theory and data-driven coding and thematic analysis via the NVivo 12 plus software.

Conclusion

From studying the complexities of the current regulatory processes for skilled migration and practitioner registration and informed by participants with first-hand knowledge and experience, this research found a clear argument for a re-examination and update of the current regulatory requirements for IQHP. Without greater innovation, harmonisation, evidence-based solutions and reform, it is likely that Australian regulators, policymakers, employers, and the nursing, midwifery and medical professions at large will continue to experience challenges in registering, employing and supporting IQHP, while maintaining the safety of the public requiring care in the Australian healthcare system.
Impact of ambient temperature on inflammation-induced encephalopathy in endotoxemic mice—role of phosphoinositide 3-kinase gamma
Authors: Lang Guang-Ping , Ndongson-Dongmo Bernadin , Lajqi Trim , Brodhun Michael , Han Yingying , Wetzker Reinhard , Frasch Martin G. , Bauer Reinhard
Published: October 2020

Background

Sepsis-associated encephalopathy (SAE) is an early and frequent event of infection-induced systemic inflammatory response syndrome. Phosphoinositide 3-kinase γ (PI3Kγ) is linked to neuroinflammation and inflammation-related microglial activity. In homeotherms, variations in ambient temperature (Ta) outside the thermoneutral zone lead to thermoregulatory responses, mainly driven by a gradually increasing sympathetic activity, and may affect disease severity. We hypothesized that thermoregulatory response to hypothermia (reduced Ta) aggravates SAE in PI3Kγ-dependent manner.

Methods

Experiments were performed in wild-type, PI3Kγ knockout, and PI3Kγ kinase-dead mice, which were kept at neutral (30 ± 0.5 °C) or moderately lowered (26 ± 0.5 °C) Ta. Mice were exposed to lipopolysaccharide (LPS, 10 μg/g, from Escherichia coli serotype 055:B5, single intraperitoneal injection)—evoked systemic inflammatory response (SIR) and monitored 24 h for thermoregulatory response and blood–brain barrier integrity. Primary microglial cells and brain tissue derived from treated mice were analyzed for inflammatory responses and related cell functions. Comparisons between groups were made with one-way or two-way analysis of variance, as appropriate. Post hoc comparisons were made with the Holm–Sidak test or t tests with Bonferroni’s correction for adjustments of multiple comparisons. Data not following normal distribution was tested with Kruskal-Wallis test followed by Dunn’s multiple comparisons test.

Results

We show that a moderate reduction of ambient temperature triggers enhanced hypothermia of mice undergoing LPS-induced systemic inflammation by aggravated SAE. PI3Kγ deficiency enhances blood–brain barrier injury and upregulation of matrix metalloproteinases (MMPs) as well as an impaired microglial phagocytic activity.

Conclusions

Thermoregulatory adaptation in response to ambient temperatures below the thermoneutral range exacerbates LPS-induced blood–brain barrier injury and neuroinflammation. PI3Kγ serves a protective role in suppressing release of MMPs, maintaining microglial motility and reinforcing phagocytosis leading to improved brain tissue integrity. Thus, preclinical research targeting severe brain inflammation responses is seriously biased when basic physiological prerequisites of mammal species such as preferred ambient temperature are ignored.
The effect of temperature on persistence of SARS-CoV-2 on common surfaces
Authors: Riddell Shane , Goldie Sarah , Hill Andrew , Eagles Debbie , Drew Trevor W.
Published: October 2020

Background

The rate at which COVID-19 has spread throughout the globe has been alarming. While the role of fomite transmission is not yet fully understood, precise data on the environmental stability of SARS-CoV-2 is required to determine the risks of fomite transmission from contaminated surfaces.

Methods

This study measured the survival rates of infectious SARS-CoV-2, suspended in a standard ASTM E2197 matrix, on several common surface types. All experiments were carried out in the dark, to negate any effects of UV light. Inoculated surfaces were incubated at 20 °C, 30 °C and 40 °C and sampled at various time points.

Results

Survival rates of SARS-CoV-2 were determined at different temperatures and D-values, Z-values and half-life were calculated. We obtained half lives of between 1.7 and 2.7 days at 20 °C, reducing to a few hours when temperature was elevated to 40 °C. With initial viral loads broadly equivalent to the highest titres excreted by infectious patients, viable virus was isolated for up to 28 days at 20 °C from common surfaces such as glass, stainless steel and both paper and polymer banknotes. Conversely, infectious virus survived less than 24 h at 40 °C on some surfaces.

Conclusion

These findings demonstrate SARS-CoV-2 can remain infectious for significantly longer time periods than generally considered possible. These results could be used to inform improved risk mitigation procedures to prevent the fomite spread of COVID-19.
African swine fever in the Lithuanian wild boar population in 2018: a snapshot
Authors: Pautienius Arnoldas , Schulz Katja , Staubach Christoph , Grigas Juozas , Zagrabskaite Ruta , Buitkuviene Jurate , Stankevicius Rolandas , Streimikyte Zaneta , Oberauskas Vaidas , Zienius Dainius , Salomskas Algirdas , Sauter-Louis Carola , Stankevicius Arunas
Published: October 2020

The first cases of African swine fever (ASF) were detected in the Lithuanian wild boar population in 2014. Since then, the disease spread slowly through the whole country, affecting both, wild boar and domestic pigs. In the other Baltic states, which both are also affected by ASF since 2014, the recent course of ASF prevalence suggests that the countries might be well under way of disease elimination. In contrast, in Lithuania the epidemic seems to be still in full progress. In the present study, we aimed to extend a previous prevalence study in Lithuania. Looking at ASF virus (ASFV) and seroprevalence estimates of wild boar in all months of 2018 and in all affected municipalities in Lithuania, the course of ASF was evaluated on a temporal and spatial scale. A non-spatial beta-binomial model was used to correct for under- or overestimation of the average prevalence estimates. Within 2018 no big differences between the prevalence estimates were seen over time. Despite of the lower sample size, highest ASFV prevalence estimates were found in dead wild boar, suggesting higher detection rates through passive surveillance than through active surveillance. Accordingly, with the maximum prevalence of 87.5% in May 2018, the ASFV prevalence estimates were very high in wild boar found dead. The number of samples originating from hunted animals (active surveillance) predominated clearly. However, the ASFV prevalence in those animals was lower with a maximum value of 2.1%, emphasizing the high value of passive surveillance. A slight increase of the seroprevalence in hunted wild boar could be seen over time. In the center of Lithuania, a cluster of municipalities with high ASFV and seroprevalence estimates was found. The results of the study indicate that ASFV is still circulating within the Lithuanian wild boar population, constituting a permanent risk of disease transmission into domestic pig holdings. However, additional, more recent data analyses are necessary to re-evaluate the course of ASF in Lithuania and thus, to be able to make a statement about the stage of the ASF epidemic in the country. This is of huge importance for Lithuania for evaluating control measures and their efficacy, but also for neighbouring countries to assess the risk of disease spread from Lithuania.
Boundarylessness and sleep quality among virtual team members – a pilot study from Germany
Authors: Rohwer Elisabeth , Kordsmeyer Ann-Christin , Harth Volker , Mache Stefanie
Published: October 2020

Background

In the course of globalisation and digitalisation, new ways of work are becoming increasingly prevalent. To remain competitive as an organisation, cooperation across time, place, and organisational boundaries is becoming necessary. Virtual teamwork offers these advantages, but can also be both, an opportunity and a burden, for employees. This pilot study aims to gain first insights into job demands and resources in virtual teamwork to provide a basis for further research from which appropriate health promotion and prevention measures can be derived.

Methods

In this pilot study, an online questionnaire was used to examine the relationship between boundarylessness as a job demand, psychological detachment as a personal resource, as well as perceived stress and sleep quality as health outcomes among 46 virtual team members from Germany. Data collection lasted from October 2019 to January 2020. Validated scales were used for the questionnaire, except for virtuality. Due to insufficient operationalisation to date, a virtuality scale was developed based on the current state of research. The data were analysed with ordinal logistic regression analyses and median split t-tests.

Results

The results indicate that perceived stress impaired sleep quality of virtual team members in this sample. In contrast, successful psychological detachment from work was positively related to sleep quality. A higher degree of virtuality coincided with higher levels of boundarylessness. Virtual team members with leadership responsibility showed higher levels of psychological detachment.

Conclusion

The present pilot study breaks ground and provides initial insights into the relationship between virtual teamwork and employee health in the German context. Further research, particularly on job demands in virtual teamwork, is needed to derive concrete health promotion and prevention measures.
A fluorescence-based high-throughput screening method for cytokinin translocation mutants
Authors: Zhang Mengyuan , Ding Bingli , Zhao Jiangzhe , Zhang Penghong , Li Yujia , Yang Guodong , Zhang Kewei
Published: October 2020

Background

Cytokinins are one kind of phytohormones essential for plant growth, development and stress responses. In the past half century, significant progresses have been made in the studies of cytokinin signal transduction and metobolic pathways, but the mechanism of cytokinin translocation is poorly understood. Arabidopsis (Arabidopsis thaliana) response regulator 5 (ARR5) is a type-A response factor in cytokinin signaling which is induced by cytokinins and has been used as a reporter gene for the endogenous cytokinins in Arabidopsis. Here, we report a fluorescence-based high-throughput method to screen cytokinin translocation mutants using an ethyl methyl sulfone (EMS) mutagenesis library generated with ARR5::eGFP transgenic plants.

Results

The seedlings with enhanced green fluorescent protein (GFP) signal in roots were screened in a luminescence imaging system (LIS) in large scale to obtain mutants with over-accumulated cytokinins in roots. The selected mutants were confirmed under a fluorescence microscopy and then performed phenotypic analysis. In this way, we obtained twelve mutants with elevated GFP signal in the roots and further found three of them displayed reduced GFP signal in the aerial tissues. Two of the mutants were characterized and proved to be the atabcg14 allelic mutants which are defective in the long-distance translocation of root-synthesized cytokinins.

Conclusions

We provide a strategy for screening mutants defective in cytokinin translocation, distribution or signaling. The strategy can be adapted to establish a system for screening mutants defective in other hormone transporters or signaling components using a fluorescence reporter.
Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma
Authors: Shamseddine Ali , Zeidan Youssef H. , El Husseini Ziad , Kreidieh Malek , Al Darazi Monita , Turfa Rim , Kattan Joseph , Khalifeh Ibrahim , Mukherji Deborah , Temraz Sally , Alqasem Kholoud , Amarin Rula , Al Awabdeh Tala , Deeba Samer , Jamali Faek , Mohamad Issa , Elkhaldi Mousa , Daoud Faiez , Al Masri Mahmoud , Dabous Ali , Hushki Ahmad , Jaber Omar , Charafeddine Maya , Geara Fady
Published: October 2020

Background

Neoadjuvant chemotherapy and short-course radiotherapy followed by resection has been gaining recognition in the treatment of rectal cancer. Avelumab is a fully human immunoglobulin that binds Programmed Death-Ligand 1 (PD-L1) and prevents the suppression of the cytotoxic T cell immune response. This phase II trial evaluates the safety and pathologic response rate of short-course radiation followed by 6 cycles of mFOLFOX6 with avelumab in patients with locally advanced rectal cancer (LARC).

Methods

This study is prospective single-arm, multicenter phase II trial adopting Simon’s two-stage. Short-course radiation is given over 5 fractions to a total dose of 25 Gy. mFOLFOX6 plus avelumab (10 mg/kg) are given every 2 weeks for 6 cycles. Total mesorectal excision is performed 3–4 weeks after the last cycle of avelumab. Follow up after surgery is done every 3 months to a total of 36 months. Adverse event data collection is recorded at every visit.

Results

13 out of 44 patients with LARC were enrolled in the first stage of the study (30% from total sample size). All patients met the inclusion criteria and received the full short-course radiation course followed by 6 cycles of mFOLFOX6 plus avelumab. 12 out of the 13 patients completed TME while one patient had progression of disease and was dropped out of the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33–73) years. The first interim analysis revealed that 3 (25%) patients achieved pathologic complete response (pCR) (tumor regression grade, TRG 0) out of 12. While 3 (25%) patients had near pCR with TRG 1. In total, 6 out of 12 patients (50%) had a major pathologic response. All patients were found to be MMR proficient. The protocol regimen was well tolerated with no serious adverse events of grade 4 reported.

Conclusion

In patients with LARC, neoadjuvant radiation followed by mFOLFOX6 with avelumab is safe with a promising pathologic response rate.

Trial Registration Number and Date of RegistrationClinicalTrials.gov NCT03503630, April 20, 2018.https://clinicaltrials.gov/ct2/show/NCT03503630?term=NCT03503630&draw=2&rank=1.
Tennis elbow, study protocol for a randomized clinical trial: needling with and without platelet-rich plasma after failure of up-to-date rehabilitation
Authors: Schwitzguebel A. J. , Bogoev M. , Nikolov V. , Ichane F. , Lädermann A.
Published: October 2020

Background

The conservative management of lateral epicondylitis is known to be a difficult-to-treat annoying condition. A treatment with platelet-rich plasma (PRP) is often performed, but its efficacy remains controversial.

Methods

This study is a single-center, randomized double-blind controlled trial, preceded by a case series. All the 232 planned patients of the case series will undergo an up-to-date comprehensive rehabilitation program, including focused extracorporeal shock waves therapy. This rehabilitation program is expected to have a maximum success rate 75%. It is therefore aimed to allocate a minimum of 58 patients with rehabilitation failure into the 1:1 randomized trial. Stratification is planned on age and lesion pattern. The masking will be quadruple (Participant, Care Provider, Investigator & Outcome Assessor). The patients will undergo an ultrasound (US)-guided needling combined with either PRP (intervention group) or saline (control group). The primary endpoint will be the pain improvement from baseline (month 0) at 3 months on a 0–10 visual analog scale (VAS) during a maximal strength isometric contraction of the extensor carpialis brevis muscle. The main secondary endpoints will include the rehabilitation success rate and improvements from baseline at 3, 6, and 12 months of the following outcomes: (i) Single Assessment Numeric Evaluation (SANE) score, (ii) Patient-Rated Tennis Elbow Evaluation (PRTEE) score, (iii) maximal grip strength on Jamar test, and (iv) the ultrasonographic evaluation of the US of the epicondylar tendons.

Discussion

The study results will provide insight into the effect of PRP as adjuvant therapy to tendon fenestration, and may contribute to identify the best preceding and concomitant rehabilitation protocol.

Trial registration

ClinicalTrials.gov NCT03987256. Registered on 20 August 2019.
Spontaneous pneumomediastinum, pneumopericardium, pneumothorax and subcutaneous emphysema in patients with COVID-19 pneumonia, a case report
Authors: Hazariwala Vikisha , Hadid Hind , Kirsch Denise , Big Cecilia
Published: October 2020

Background

Spontaneous pneumomediastinum unrelated to mechanical ventilation is a newly described complication of COVID-19 pneumonia. The objective of this case presentation is to highlight an important complication and to explore potential predisposing risk factors and possible underlying pathophysiology of this phenomenon.

Case presentation

We present two patients with COVID-19 pneumonia complicated by spontaneous pneumomediastinum, pneumopericardium, pneumothorax and subcutaneous emphysema without positive pressure ventilation. Both patients had multiple comorbidities, received a combination of antibiotics, steroids and supportive oxygen therapy, and underwent routine laboratory workup. Both patients then developed spontaneous pneumomediastinum and ultimately required intubation and mechanical ventilation, which proved to be challenging to manage.

Conclusions

Spontaneous pneumomediastinum is a serious complication of COVID-19 pneumonia, of which clinicians should be aware. Further studies are needed to determine risk factors and laboratory data predictive of development of spontaneous pneumomediastinum in COVID-19 pneumonia.
Near-infrared intraoperative imaging with indocyanine green is beneficial in video-assisted thoracoscopic segmentectomy for patients with chronic lung diseases: a retrospective single-center propensity-score matched analysis
Authors: Liu Zhengcheng , Yang Rusong , Cao Hui
Published: October 2020

Objective

To investigate whether video-assisted thoracoscopic segmentectomy using near-infrared fluorescence imaging had better intersegmental plane visualization and peri-operative outcome in patients with chronic lung diseases.

Methods

Data were collected retrospectively from March 2014 and August 2019. A total of 92 patients with pulmonary nodules underwent near-infrared fluorescence guided uni-port thoracoscopic segmentectomy(NIF-VATS), 149 patients underwent thoracoscopic segmentectomy with inflation-deflation method(ID-VATS). After 1:1 propensity matching, perioperative outcomes between NIF-VATS and ID-VATS was compared.

Results

Incision size was 3 cm in both group.Mean operative time was 79 min in NIF-VATS group and 96 min in ID-VATS group. The intersegmental plane was not clear in 33 cases of ID-VATS group, and no clear boundary was found after prolonged waiting time. Emphysema or pulmonary bullae could be found in chest CT scan in these patients, they all were diagnosed as chronic obstructive pulmonary disease. In NIF-VATS group, the intersegmental plane was not clear in 8 cases. Under the guidance of three-dimensional reconstruction and preoperative positioning, the oncological margin length of both groups met the requirements of surgical quality control. The intraoperative blood loss, number of lymph node resection, showed no statistical difference between the two groups. Postoperative air leakage was more often observed in ID-VATS group. The postoperative drainage duration, postoperative hospitalization time was shorter in ID-VATS group.

Conclusions

Compared with inflation-deflation method, segmentectomy using NIF imaging is feasible for patients with chronic lung diseases with better intersegmental plane, shorter operation time, less complications, it might lead to faster recovery.
Incidence, risk factors and clinical outcomes of acute kidney injury after heart transplantation: a retrospective single center study
Authors: Jiang Yi-Yao , Kong Xiang-Rong , Xue Fen-Long , Chen Hong-Lei , Zhou Wei , Chai Jun-Wu , Wu Fei , Jiang Shan-Shan , Li Zhi-Long , Wang Kai
Published: October 2020

Objectives

This study aimed to identify the incidence rate of Acute kidney injury (AKI) in our center and predict in-hospital mortality and long-term survival after heart transplantation (HTx).

Methods

This single-center, retrospective study from October 2009 and March 2020 analyzed the pre-, intra-, and postoperative characteristics of 95 patients who underwent HTx. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Risk factors were analyzed by multivariable logistic regression models. The log-rank test was used to compare long-term survival.

Results

Thirty-three (34.7%) patients developed AKI. The mortality in hospital in HTx patients with and without AKI were 21.21 and 6.45%, respectively (P < 0.05). Recipients in AKI who required renal replacement therapy (RRT) had a hospital mortality rate of 43.75% compared to 6.45% in those without AKI or RRT (P < 0.0001). A long cardiopulmonary bypass (CPB) time (OR:11.393, 95% CI: 2.183 to 59.465,P = 0.0039) was positively related to the occurrence of AKI. A high intraoperative urine volume (OR: 0.031, 95% CI: 0.005 to 0.212,P = 0.0004) was negatively correlated with AKI. AKI requiring RRT (OR, 11.348; 95% CI, 2.418–53.267,P = 0.002) was a risk factor for mortality in hospital. Overall survival in patients without AKI at 1 and 3 years was not different from that in patients with AKI (P = 0.096).

Conclusions

AKI is common after HTx. AKI requiring RRT could contribute powerful prognostic information to predict mortality in hospital. A long CPB time and low intraoperative urine volume are associated with the occurrence of AKI.
Development and evaluation of indirect enzyme-linked immunosorbent assays for the determination of immune response to multiple clostridial antigens in vaccinated captive bred southern white rhinoceros (Ceratotherium simum simum)
Authors: Buys Angela , Crafford Jannie , van Heerden Henriette
Published: October 2020

Background

An overall increase in poaching of white rhinoceros results in captive breeding becoming a significant component of white rhinoceros conservation. However, this type of conservation comes with its own difficulties. When wildlife is captured, transported and/or confined to a boma environment, they are more predisposed to diseases caused by bacterial organisms such as spore forming Clostridium spp. A southern white rhinoceros (Ceratotherium simum simum) population on a captive bred farm was suspected to be affected by Clostridium infections. These endangered animals were apparently exposed to Clostridium spp., in the conservation area previously used for cattle farming. The rhinoceros population on the breeding operation property was vaccinated with a multi-component clostridial vaccine registered for use in cattle. Multiple indirect enzyme-linked immunosorbent assays (iELISAs) were developed in order to evaluate the serum antibody titres of these vaccinated animals. In evaluating vaccine efficacy, the gold standard mouse neutralization test (MNT) was not available and therefore iELISAs were developed for the detection of serum antibodies to C. perfringens type A (alpha toxin), C. chauvoei (whole cell), C. novyi (alpha toxin), C. septicum (alpha toxin) and C. sordellii (lethal toxin) in the white rhinoceros population using international reference sera of equine origin. Antibody titres against each clostridial antigen was evaluated in the vaccinated white rhinoceros population (n = 75). Analytical specificity showed slight cross-reactions for C. chauvoei and C. perfringens type A with the other antigens. Individual assay cut-off values were calculated with 95% confidence. Coefficient of variance (CV) values for both the international reference sera and in-house control sera across all the antigens were well below 16%, indicating good assay repeatability. This convenient and fast assay is suitable for monitoring humoral immune responses to clostridial antigens in vaccinated white rhinoceroses.

Results

Checkerboard titrations indicated optimal antigen and antibody concentrations to be used for each respective iELISA developed. Each titration set of the respective international reference and in-house control sera showed good repeatability with low standard deviations and coefficient of variance values calculated between repeats for each antigen. Individual assays proved repeatable and showed good analytical sensitivity and specificity.

Conclusions

The developed iELISAs are able to evaluate antibody profiles of phospholipase C, C. chauvoei whole cells, TcnA, ATX, TcsL in white rhinoceros serum using international reference sera.
‘Mothers moving towards empowerment’ intervention to reduce stigma and improve treatment adherence in pregnant women living with HIV in Botswana: study protocol for a pragmatic clinical trial
Authors: Poku Ohemaa B. , Ho-Foster Ari R. , Entaile Patlo , Misra Supriya , Mehta Haitisha , Rampa Shathani , Goodman Melody , Arscott-Mills Tonya , Eschliman Evan , Jackson Valerie , Melese Tadele , Becker Timothy D. , Eisenberg Marlene , Link Bruce , Go Vivian , Opondo Philip Renison , Blank Michael B. , Yang Lawrence H.
Published: October 2020

Background

With high rates of HIV and multiple vulnerable subgroups across diverse settings, there is a need for culturally based, HIV stigma reduction interventions. Pregnant women who are living with HIV are especially in need of services to protect not only their own but also their children’s lives. Uptake of HIV services worldwide is hindered by stigma towards persons living with HIV/AIDS. While cultural context plays a key role in shaping HIV stigma, these insights have not yet been fully integrated into stigma reduction strategies. By utilizing the “What Matters Most” stigma framework, we propose that an intervention to counter culturally salient aspects of HIV stigma will improve treatment adherence and other relevant outcomes. A pragmatic clinical trial in Botswana will evaluate the “Mothers Moving towards Empowerment” (MME) intervention, which seeks to address HIV stigma in Botswana and to specifically engage pregnant mothers so as to promote antiretroviral therapy (ART) adherence in the postpartum period.

Methods

This study will test MME against treatment as usual (TAU) among pregnant mothers diagnosed with HIV and their infants. Outcomes will be assessed during pregnancy and 16 weeks postpartum. Women who meet eligibility criteria are assigned to MME or TAU. Women assigned to MME are grouped with others with similar estimated delivery dates, completing up to eight intervention group sessions scheduled before week 36 of their pregnancies. Primary outcomes among mothers include (i) reducing self-stigma, which is hypothesized to mediate improvements in (ii) psychological outcomes (quality of life, depression and social functioning), and (iii) adherence to antenatal care and ART. We will also examine a set of follow-up infant birth outcomes (APGAR score, preterm delivery, mortality (at < 16 weeks), birth weight, vaccination record, and HIV status).

Discussion

Our trial will evaluate MME, a culturally based HIV stigma reduction intervention using the “What Matters Most” framework, to reduce stigma and improve treatment adherence among pregnant women and their infants. This study will help inform further refinement of MME and preparation for a future large-scale, multisite, randomized controlled trial (RCT) in Botswana.

Trial registration

ClinicalTrials.gov NCT03698981. Registered on October 8, 2018
Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial
Authors: Bradley Ryan , Langley Blake O. , Ryan Jennifer J. , Phipps John , Hanes Douglas A. , Stack Emily , Jansson Janet K. , Metz Thomas O. , Stevens Jan Frederik
Published: October 2020

Background

Natural products may provide a source for the discovery and development of adjunctive pharmacological interventions to modulate the inflammatory pathways contributing to chronic disease. Xanthohumol, a flavonoid from the hops plant (Humulus lupulus), has antioxidant and anti-inflammatory properties and may act as a prebiotic to the intestinal microbiota. Xanthohumol is not currently approved as a drug by the US Food and Drug Administration (FDA), but is available as a dietary supplement and ingredient in medical foods. To formally test the safety of xanthohumol, a phase I clinical trial (“XMaS”) was designed and approved under an Investigational New Drug application to the US FDA. The main objective is to examine the clinical safety and subjective tolerability of xanthohumol in healthy adults compared to placebo. Additional aims are to monitor biomarkers related to inflammation, gut permeability, bile acid metabolism, routes, and in vivo products of xanthohumol metabolism, and to evaluate xanthohumol’s impact on gut microbial composition.

Methods

The safety and tolerability of xanthohumol in healthy adults will be evaluated in a triple-masked, randomized, placebo-controlled trial. Participants will be randomized to either 24 mg/day of xanthohumol or placebo for 8 weeks. Blood cell counts, hepatic and renal function tests, electrolytes, and self-reported health-related quality of life measures will be collected every 2 weeks. Participants will be queried for adverse events throughout the trial. Xanthohumol metabolites in blood, urine, and stool will be measured. Biomarkers to be evaluated include plasma tumor necrosis factor-alpha, various interleukins, soluble CD14, lipopolysaccharide-binding protein, fecal calprotectin, and bile acids to assess impact on inflammatory and gut permeability-related mechanisms in vivo. Stool samples will be analyzed to determine effects on the gut microbiome.

Discussion

This phase I clinical trial of xanthohumol will assess safety and tolerability in healthy adults, collect extensive biomarker data for assessment of potential mechanism(s), and provide comparison data necessary for future phase II trials in chronic disease(s). The design and robustness of the planned safety and mechanistic evaluations planned provide a model for drug discovery pursuits from natural products.

Trial registration

ClinicalTrials.gov NCT03735420. Registered on November 8, 2018
Human placental extract attenuates neurological symptoms in the experimental autoimmune encephalomyelitis model of multiple sclerosis-a putative approach in MS disease?
Authors: Jazayeri Mir Hadi , barzaman Khadijeh , Nedaeinia Reza , Aghaie Tayebe , Motallebnezhad Morteza
Published: October 2020

Background

Different studies have demonstrated the anti-inflammatory effects of human placental extract both in vivo and in vitro. Considering the chronic inflammatory nature of multiple sclerosis (MS) disease, we examined whether or not the administration of human placental extract is able to attenuate the neurological symptoms detected in experimental autoimmune encephalomyelitis (EAE) model of MS.

Methods

The injected myelin oligodendrocyte glycoprotein (MOG) induced EAE in mice, and treatment began from day 4 post-injection by intraperitoneal administration of 20 mg/kg human placental extract, repeated every other day up to day 31 post-injection. At the end of the treatment, luxol fast blue (LBS) staining and hematoxylin and eosin (H&E) staining were performed to evaluate the demyelination of neurons and inflammatory responses, respectively. Further assessed were the serum concentrations of IL-23 and IL-27.

Results

The administration of human placental extract was able to significantly reduce the mean clinical score in EAE mice, decrease the pro-inflammatory process and attenuate neural demyelination. Moreover, while the serum concentration of IL-23 was significantly diminished in the EAE mice receiving human placental extract compared to the non-treated EAE group, IL-27 concentration was significantly increased.

Conclusions

Our findings demonstrated the administration of human placental extract could significantly attenuate the neurological symptoms in the EAE model of MS in part through modulating the serum levels of IL-23 and IL-27 and enhancing neuroprotection and myelin repair.
Zinc uptake system ZnuACB is essential for maintaining pathogenic phenotype of F4ac+ enterotoxigenic E. coli (ETEC) under a zinc restricted environment
Authors: Quan Guomei , Xia Pengpeng , Lian Siqi , Wu Yunping , Zhu Guoqiang
Published: October 2020

Zinc is the second trace element of living organisms after iron. Given its crucial importance, mammalian hosts restrict the bioavailability of Zinc ions (Zn2+) to bacterial pathogens. As a countermeasure, pathogens utilize high affinity Zn2+ transporters, such as ZnuACB to compete with the host for zinc. It is essential for bacteria to maintain zinc homeostasis and thus maintain their physiology and pathogenesis. In an attempt to uncover the zinc transporter in F4+ enterotoxigenic E. coli (ETEC) C83902, we analyzed two RNA-seq data sets of bacteria samples when different zinc treatments (restriction or abundance) were applied. Considering data revealing that the high affinity zinc uptake system ZnuACB acts as the main transporter in ETEC C83902 to resist zinc deficiency, we deleted znuACB genes to study the role of them in ETEC C83902. The deletion of znuACB genes results in growth perturbation and a sharp decrease in the ability of biofilm formation and adhesion of bacteria in vitro. Taking the data together, this study demonstrates that the ZnuACB system is required for ETEC C83902 to acquire zinc, which highly contributes to ETEC pathogenicity as well.
Nigella A ameliorates inflammation and intestinal flora imbalance in DSS induced colitis mice
Authors: Hu Xingjiang , Xu Nana , Yang Xi , Hu Xi , Zheng Yunliang , Zhang Qiao
Published: October 2020

Nigella A, also named Sieboldianoside A, has been extracted from many kinds of Traditional Chinese Medicine (TCM), such as Nigella glandulifera, Stauntonia chinensis DC., and the leaves of Acanthopanax sieboldianus. Nigella A exhibited potential analgesic, anti-inflammatory, anti-tumor, and antioxidant activities. However, whether Nigella A could treat ulcerative colitis (UC) is still unknown. As saponins always be regarded as the kinds of ingredients that could regulate immunity and intestinal flora. This research aimed to investigate the therapeutic effect of Nigella A on UC and explore its effect on intestinal flora. We noted that Nigella A and Sulfasalazine (SASP) could significantly improve the signs and symptoms, alleviate colonic pathological injury in DSS-induced mice. The changing of many specific bacterial genus such as Lactobacillus, Porphyromonadaceae, Bacteroides and Escherichia might closely related to the recovery of intestinal inflammatory response. This study initially confirmed the therapeutic effect of Nigella A and SASP on DSS-induced colitis by improving the diversity of intestinal microbial composition. Nigella A has the potential to be developed for the treatment of UC and other disorders related to the imbalance of intestinal flora.
A fourth-order cumulant orthonormal propagator rooting method based on Toeplitz approximation
Authors: Shi Heping , Ma Ning , Guan Zhiwei , Zhang Lizhu , Jiang Shan
Published: October 2020

A novel Toeplitz fourth-order cumulant (FOC) orthonormal propagator rooting method (TFOC ‐ OPRM) of direction-of-arrival (DOA) estimation for uniform linear array (ULA) is proposed in this paper. Specifically, the modified (i.e., reduced-dimension)FOC  (MFOC) matrix is achieved at first via removing the redundant information encompassed in the primaryFOCmatrix; then, theTFOCmatrix which possesses Toeplitz structure can be recovered by utilizing the Toeplitz approximation method. To reduce the computational complexity, an effective method based on the polynomial rooting technology is adopted. Finally, the DOAs of incident signals can be estimated by exploiting orthonormal propagator rooting method. The theoretical analysis coupled with simulation results show that the proposed resultant algorithm can reduce the computational complexity significantly, as well as improve the estimation performance in both spatially white noise environment and spatially color noise environment.
Outcomes after corrective surgery for congenital dextro-transposition of the arteries using the arterial switch technique: a scoping systematic review
Authors: Morfaw Frederick , Leenus Alvin , Mbuagbaw Lawrence , Anderson Laura N. , Dillenburg Rejane , Thabane Lehana
Published: October 2020

Background

Dextro-transposition of the great arteries (d-TGA) is the most frequent cyanotic congenital heart pathology in neonates. Surgical correction of this condition is possible using the arterial switch operation (ASO) which was first performed by Jatene in 1975.

Objectives

The aim of this study was to summarise the evidence on short- (less than 1 year), medium- (1–20 years), and long-term (more than 20 years) outcomes of children withd-TGA treated with the ASO. The primary outcome was survival. Secondary outcomes were freedom from cardiac reoperations, occurrence of aortic insufficiency, pulmonary stenosis, coronary artery anomalies, neuropsychological development problems and quality of life.

Methods

We searched MEDLINE, EMBASE, CINAHL, LILACS, and reference lists of included articles for studies reporting outcomes after ASO ford-TGA. Screening, data extraction and risk of bias assessment were done independently by two reviewers. We pooled data using a random-effects meta-analysis of proportions and, where not possible, outcomes were synthesized narratively. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the certainty of the evidence for each outcome.

Main results

Following ASO for TGA, short-term survival was 92.0% (95% CI 91.0–93.0%;I2= 85.8%, 151 studies, 30,186 participants; moderate certainty evidence). Medium-term survival was 90.0% (95% CI 89.0–91.0%;I2= 84.3%, 133 studies; 23,686 participants, moderate certainty evidence), while long-term survival was 87.0% (95% CI 80.0–92.0 %;I2= 84.5%, 4 studies, 933 participants, very low certainty evidence). Evaluation of the different secondary outcomes also showed satisfactory results in the short, medium and long term. Subgroup analysis suggests slightly higher survival following ASO for TGA in the second surgical era (1998 to 2018) than in the first surgical era (1975 to 1997) in the short and medium term [93.0% (95% CI 92.0–94.0) vs 90.0% (95% CI 89.0–92.0) and 93.0% (95% CI 91.0–94.0) vs 88.0% (87.0–90.0%) respectively] but not in the long term [81.0% (95% CI 76.0–86.0%) vs 89.0% (80.0–95.0%)].

Conclusions

Pooled data from many sources suggests that the ASO ford-TGA leads to high rates of survival in the short, medium, and long term.
Low Mach number limit for the compressible Navier–Stokes equations with density-dependent viscosity and vorticity-slip boundary condition
Authors: Ren Dandan , Ding Yunting , Liang Xinfeng
Published: October 2020

In this paper, we consider the three-dimensional compressible Navier–Stokes equations with density-dependent viscosity and vorticity-slip boundary condition in a bounded smooth domain. The main idea is to derive the uniform estimates for both time and the Mach number. The difficulty is dealing with density-dependent viscosity terms carefully. With the uniform estimates, we can verify the low Mach limit of the global strong solutions of compressible Navier–Stokes equations and the global existence and uniqueness of the strong solution of incompressible Navier–Stokes equations around a steady state.
Multiplicity results for sublinear elliptic equations with sign-changing potential and general nonlinearity
Authors: He Wei , Wu Qingfang
Published: October 2020

In this paper, we study the following elliptic boundary value problem:
$$ \textstyle\begin{cases} -\Delta u+V(x)u=f(x, u),\quad x\in \Omega , \\ u=0, \quad x \in \partial \Omega , \end{cases} $$

{

−
Δ
u
+
V
(
x
)
u
=
f
(
x
,
u
)
,

x
∈
Ω
,

u
=
0
,

x
∈
∂
Ω
,

where $\Omega \subset {\mathbb {R}}^{N}$
Ω
⊂

R
N

is a bounded domain with smooth boundary ∂Ω, and f is allowed to be sign-changing and is of sublinear growth near infinity in u. For both cases that $V\in L^{N/2}(\Omega )$
V
∈

L

N
/
2

(
Ω
)
with $N\geq 3$
N
≥
3
and that $V\in C(\Omega , \mathbb {R})$
V
∈
C
(
Ω
,
R
)
with $\inf_{\Omega }V(x)>-\infty $

inf
Ω

V
(
x
)
>
−
∞
, we establish a sequence of nontrivial solutions converging to zero for above equation via a new critical point theorem.
The step-type contrast structure for a second order semi-linear singularly perturbed differential-difference equation
Authors: Xu Mei , Wang Bingxian
Published: October 2020

The step-type contrast structure for a second order semi-linear singularly perturbed differential-difference equation is studied. Using the methods of boundary function and fractional steps, we construct the formula asymptotic expansion of the problem. At the same time, based on sewing techniques, the existence of the step-type contrast structure solution and the uniform validity of the asymptotic expansion are proved.
Time-continuous and time-discrete SIR models revisited: theory and applications
Authors: Wacker Benjamin , Schlüter Jan
Published: October 2020

Since Kermack and McKendrick have introduced their famous epidemiological SIR model in 1927, mathematical epidemiology has grown as an interdisciplinary research discipline including knowledge from biology, computer science, or mathematics. Due to current threatening epidemics such as COVID-19, this interest is continuously rising. As our main goal, we establish an implicit time-discrete SIR (susceptible people–infectious people–recovered people) model. For this purpose, we first introduce its continuous variant with time-varying transmission and recovery rates and, as our first contribution, discuss thoroughly its properties. With respect to these results, we develop different possible time-discrete SIR models, we derive our implicit time-discrete SIR model in contrast to many other works which mainly investigate explicit time-discrete schemes and, as our main contribution, show unique solvability and further desirable properties compared to its continuous version. We thoroughly show that many of the desired properties of the time-continuous case are still valid in the time-discrete implicit case. Especially, we prove an upper error bound for our time-discrete implicit numerical scheme. Finally, we apply our proposed time-discrete SIR model to currently available data regarding the spread of COVID-19 in Germany and Iran.
Identifying the space source term problem for time-space-fractional diffusion equation
Authors: Karapinar Erdal , Kumar Devendra , Sakthivel Rathinasamy , Luc Nguyen Hoang , Can N. H.
Published: October 2020

In this paper, we consider an inverse source problem for the time-space-fractional diffusion equation. Here, in the sense of Hadamard, we prove that the problem is severely ill-posed. By applying the quasi-reversibility regularization method, we propose by this method to solve the problem (1.1). After that, we give an error estimate between the sought solution and regularized solution under a prior parameter choice rule and a posterior parameter choice rule, respectively. Finally, we present a numerical example to find that the proposed method works well.
The Nehari manifold method for discrete fractional p-Laplacian equations
Authors: Ju Xuewei , Die Hu , Xiang Mingqi
Published: October 2020

The aim of this paper is to investigate the multiplicity of homoclinic solutions for a discrete fractional difference equation. First, we give a variational framework to a discrete fractional p-Laplacian equation. Then two nontrivial and nonnegative homoclinic solutions are obtained by using the Nehari manifold method.
Some expansion formulas for incomplete H- and H̅-functions involving Bessel functions
Authors: Meena Sapna , Bhatter Sanjay , Jangid Kamlesh , Purohit Sunil Dutt
Published: October 2020

In this paper, we assess an integral containing incomplete H-functions and utilize it to build up an expansion formula for the incomplete H-functions including the Bessel function. Next, we evaluate an integral containing incomplete H̅-functions and use it to develop an expansion formula for the incomplete H̅-functions including the Bessel function. The outcomes introduced in this paper are general in nature, and several particular cases can be acquired by giving specific values to the parameters engaged with the principle results. As particular cases, we derive expansions for the incomplete Meijer ${}^{(\Gamma )}G$

G

(
Γ
)

-function, Fox–Wright ${}_{p}\Psi _{q}^{(\Gamma )}$

Ψ
q

(
Γ
)

p

-function, and generalized hypergeometric ${}_{p}\Gamma _{q}$

Γ
q

p

function.
Identities on poly-Dedekind sums
Authors: Kim Taekyun , Kim Dae San , Lee Hyunseok , Jang Lee-Chae
Published: October 2020

Dedekind sums occur in the transformation behavior of the logarithm of the Dedekind eta-function under substitutions from the modular group. In 1892, Dedekind showed a reciprocity relation for the Dedekind sums. Apostol generalized Dedekind sums by replacing the first Bernoulli function appearing in them by any Bernoulli functions and derived a reciprocity relation for the generalized Dedekind sums. In this paper, we consider the poly-Dedekind sums obtained from the Dedekind sums by replacing the first Bernoulli function by any type 2 poly-Bernoulli functions of arbitrary indices and prove a reciprocity relation for the poly-Dedekind sums.