bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse events with sacubitril/valsartan in the real world: emerging signals to target preventive strategies from the FDA adverse event reporting system
Authors: Gatti Milo , Antonazzo Ippazio Cosimo , Diemberger Igor , De Ponti Fabrizio , Raschi Emanuel
Published: April 2020

Aims

The aim of this study was to characterise clinical priority of adverse events with sacubitril/valsartan for targeting preventive measures.

Methods

We used the US Food and Drug Administration adverse event reporting system (worldwide pharmacovigilance database) to compare adverse events recording sacubitril/valsartan as suspect with other cardiovascular drugs. Disproportionality analyses were performed by calculating the reporting odds ratios, deemed significant when the lower limit of the 95% confidence interval was greater than 1. Clinical priority was assigned to adverse events with significant disproportionality by scoring (range 0–10 points) five features (number of events, magnitude of the lower limit of the 95% confidence interval, mortality frequency, important/designated medical event, biological plausibility).

Results

Sacubitril/valsartan was recorded in 20,021 reports, with 178 adverse events associated with significant disproportionality: 71.9%, 25.9% and 2.2% were classified as weak, moderate and strong clinical priorities, respectively. Increased reporting emerged for several cardiovascular adverse events, including ‘renal failure’ (N = 388; lower limit of the 95% confidence interval 2.26), ‘hyperkalaemia’ (314; 2.42) and ‘angioedema’ (309; 1.56). Sudden cardiac death (priority score 9 points) was the only designated medical event with strong clinical priority. Notably, sudden cardiac death occurred early after sacubitril/valsartan administration (average onset 124 days), with concomitant drugs known for pro-arrhythmic potential (e.g. amiodarone, escitalopram, mirtazapine, loop diuretics) in 26.2% of records.

Conclusion

The increased cardiovascular reporting of sacubitril/valsartan in the real world was largely predictable from pre-approval evidence, underlying disease and likely patients’ comorbidities. The unexpected reporting of sudden cardiac death occurred well before the complete development of positive electrical remodelling induced by sacubitril/valsartan, and calls for stringent clinical monitoring (to reduce the pro-arrhythmic burden related to co-medications), and further investigation on appropriate combination with other preventive measures.
Who Influences Urban Students’ College Aspirations? Evidence From the Fifth Largest School District in the United States
Authors: Martinez Magdalena , Brekken Katheryn , Bernick E. Lee
Published: April 2020

This study explored students’ perceptions about school counselor influence on college aspirations in the fifth largest school district in the nation. Using 2015 survey data from 12th graders, the findings indicated that students who selected their school counselor as the most helpful person for college advice were more likely to intend to go to college, as compared to students who selected other individuals. Practical implications highlight the important role of school counselors in urban districts with significant first-generation college student populations.
Affective Dynamics Across Internalizing and Externalizing Dimensions of Psychopathology
Authors: Scott Lori N. , Victor Sarah E. , Kaufman Erin A. , Beeney Joseph E. , Byrd Amy L. , Vine Vera , Pilkonis Paul A. , Stepp Stephanie D.
Published: April 2020

Little is known about pathogenic affective processes that cut across diverse mental disorders. We examine how dynamic features of positive and negative affect differ or converge across internalizing and externalizing disorders in a diagnostically diverse urban sample using bivariate dynamic structural equation modeling. One-hundred fifty-six young women completed semistructured clinical interviews and a 21-day ecological momentary assessment protocol with seven assessments of affective states per day. Internalizing and externalizing dimensions of psychopathology were modeled using confirmatory factor analysis of mental disorders. After controlling for externalizing disorders, internalizing disorders were associated with higher negative affective mean intensity, higher negative affective variability (i.e., unique innovation variance), and lower positive affective variability. Conversely, externalizing disorders were associated with less persistent positive affect (i.e., lower inertia) and more variable positive emotionality. Results suggest internalizing and externalizing disorders have distinct affective dynamic signatures, which have implications for development of tailored interventions.
Protocol: The Lacunar Intervention Trial 2 (LACI-2). A trial of two repurposed licenced drugs to prevent progression of cerebral small vessel disease
Authors: Wardlaw Joanna , Bath Philip M W , Doubal Fergus , Heye Anna , Sprigg Nikola , Woodhouse Lisa J , Blair Gordon , Appleton Jason , Cvoro Vera , England Timothy , Hassan Ahamad , John Werring David , Montgomery Alan ,   The LACI-2 Trial Investigators
Published: April 2020

Background

Small vessel disease causes a quarter of ischaemic strokes (lacunar subtype), up to 45% of dementia either as vascular or mixed types, cognitive impairment and physical frailty. However, there is no specific treatment to prevent progression of small vessel disease.

Aim

We designed the LACunar Intervention Trial-2 (LACI-2) to test feasibility of a large trial testing cilostazol and/or isosorbide mononitrate (ISMN) by demonstrating adequate participant recruitment and retention in follow-up, drug tolerability, safety and confirm outcome event rates required to power a phase 3 trial.

Methods and design

LACI-2 is an investigator-initiated, prospective randomised open label blinded endpoint (PROBE) trial aiming to recruit 400 patients with prior lacunar syndrome due to a small subcortical infarct. We randomise participants to cilostazol v no cilostazol and ISMN or no ISMN, minimising on key prognostic factors. All patients receive guideline-based best medical therapy. Patients commence trial drug at low dose, increment to full dose over 2–4 weeks, continuing on full dose for a year. We follow-up participants to one year for symptoms, tablet compliance, safety, recurrent vascular events, cognition and functional outcomes, Trails B and brain MRI. LACI-2 is registered ISRCTN 14911850, EudraCT 2016–002277-35. Trial outcome: Primary outcome is feasibility of recruitment and compliance; secondary outcomes include safety (cerebral or systemic bleeding, falls, death), efficacy (recurrent cerebral and cardiac vascular events, cognition on TICS, Trails B) and tolerability.

LACI-2 will determine feasibility, tolerability and provide outcome rates to power a large phase 3 trial to prevent progression of cerebral small vessel disease.
Sonography of the Lungs: Diagnosis and Surveillance of Patients With COVID-19
Authors: Evans Kevin D. , Yang Qian , Liu Yang , Ye Ruizhong , Peng Chengzhong
Published: April 2020

The outbreak of a novel coronavirus (COVID-19) with symptoms that mimic bronchitis and other chest infections has created a need for quick diagnosis to prevent disease spread. Traditionally, computed tomography (CT) has been used as the primary method to identify infection and staging of the virus. While effective, repeated use of ionizing radiation, particularly in susceptible patient populations, can add risk as the disease is monitored through full recovery. Sonography of the chest may be a viable alternative for diagnosis and monitoring of COVID-19. In addition, new technology such as the remote robotic ultrasound equipment being used at Zhejiang Provincial People’s Hospital in Hangzhou, China, has the potential to facilitate sonographic evaluation with minimal disease exposure to the sonologist and to other patients by eliminating the need for patient transport to imaging facilities. Additional studies will need to be conducted to evaluate the effectiveness of sonography versus other imaging modalities in the diagnosis and treatment of COVID-19 and other novel diseases.
Low-cost, easy-to-build noninvasive pressure support ventilator for under-resourced regions: open source hardware description, performance and feasibility testing
Authors: Garmendia Onintza , Rodríguez-Lazaro Miguel A. , Otero Jorge , Phan Phuong , Stoyanova Alexandrina , Dinh-Xuan Anh Tuan , Gozal David , Navajas Daniel , Montserrat Josep M. , Farré Ramon
Published: April 2020

Aim

Current pricing of commercial mechanical ventilators in low-/middle-income countries (LMICs) markedly restricts their availability, and consequently a considerable number of patients with acute/chronic respiratory failure cannot be adequately treated. Our aim was to design and test an affordable and easy-to-build noninvasive bilevel pressure ventilator to allow a reduction in the serious shortage of ventilators in LMICs.

Methods

The ventilator was built using off-the-shelf materials availableviae-commerce and was based on a high-pressure blower, two pressure transducers and an Arduino Nano controller with a digital display (total retail cost <75 USD), with construction details provided open source for free replication. The ventilator was evaluated, and compared with a commercially available device (Lumis 150 ventilator; Resmed, San Diego, CA, USA): 1) in the bench setting using an actively breathing patient simulator mimicking a range of obstructive/restrictive diseases; and b) in 12 healthy volunteers wearing high airway resistance and thoracic/abdominal bands to mimic obstructive/restrictive patients.

Results

The designed ventilator provided inspiratory/expiratory pressures up to 20/10 cmH2O, respectively, with no faulty triggering or cycling; both in the bench test and in volunteers. The breathing difficulty score rated (1–10 scale) by the loaded breathing subjects was significantly (p<0.005) decreased from 5.45±1.68 without support to 2.83±1.66 when using the prototype ventilator, which showed no difference with the commercial device (2.80±1.48; p=1.000).

Conclusion

The low-cost, easy-to-build noninvasive ventilator performs similarly to a high-quality commercial device, with its open-source hardware description, which will allow for free replication and use in LMICs, facilitating application of this life-saving therapy to patients who otherwise could not be treated.
EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke
Authors: Bassetti Claudio L.A. , Randerath Winfried , Vignatelli Luca , Ferini-Strambi Luigi , Brill Anne-Kathrin , Bonsignore Maria R. , Grote Ludger , Jennum Poul , Leys Didier , Minnerup Jens , Nobili Lino , Tonia Thomy , Morgan Rebecca , Kerry Joel , Riha Renata , McNicholas Walter T. , Papavasileiou Vasileios
Published: April 2020

Sleep disorders are highly prevalent in the general population and may be linked in a bidirectional fashion to stroke, which is one of the leading causes of morbidity and mortality.

Four major scientific societies established a task force of experts in neurology, stroke, respiratory medicine, sleep medicine and methodology, to critically evaluate the evidence regarding potential links and the impact of therapy. 13 research questions were evaluated in a systematic literature search using a stepwise hierarchical approach: first, systematic reviews and meta-analyses; second, primary studies post-dating the systematic reviews/meta-analyses. A total of 445 studies were evaluated and 88 included. Statements were generated regarding current evidence and clinical practice.

Severe obstructive sleep apnoea (OSA) doubles the risk for incident stroke, especially in young to middle-aged patients. Continuous positive airway pressure (CPAP) may reduce stroke risk, especially in treatment-compliant patients. The prevalence of OSA is high in stroke patients and can be assessed by polygraphy. Severe OSA is a risk factor for recurrence of stroke and may be associated with stroke mortality, while CPAP may improve stroke outcome. It is not clear if insomnia increases stroke risk, while pharmacotherapy of insomnia may increase it. Periodic limb movements in sleep (PLMS), but not restless limb syndrome (RLS), may be associated with an increased risk of stroke. Preliminary data suggest a high frequency of post-stroke insomnia and RLS and their association with a less favourable stroke outcome, while treatment data are scarce.

Overall, the evidence base is best for OSA relationship with stroke and supports active diagnosis and therapy. Research gaps remain especially regarding insomnia and RLS/PLMS relationships with stroke.
Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome
Authors: Thurman Angela John , Potter Laura A. , Kim Kyoungmi , Tassone Flora , Banasik Amy , Potter Sarah Nelson , Bullard Lauren , Nguyen Vivian , McDuffie Andrea , Hagerman Randi , Abbeduto Leonard
Published: April 2020

Background

The purpose of this study was to conduct a 20-week controlled trial of lovastatin (10 to 40 mg/day) in youth with fragile X syndrome (FXS) ages 10 to 17 years, combined with an open-label treatment of a parent-implemented language intervention (PILI), delivered via distance video teleconferencing to both treatment groups, lovastatin and placebo.

Method

A randomized, double-blind trial was conducted at one site in the Sacramento, California, metropolitan area. Fourteen participants were assigned to the lovastatin group; two participants terminated early from the study. Sixteen participants were assigned to the placebo group. Lovastatin or placebo was administered orally in a capsule form, starting at 10 mg and increasing weekly or as tolerated by 10 mg increments, up to a maximum dose of 40 mg daily. A PILI was delivered to both groups for 12 weeks, with 4 activities per week, through video teleconferencing by an American Speech-Language Association-certified Speech-Language Pathologist, in collaboration with a Board-Certified Behavior Analyst. Parents were taught to use a set of language facilitation strategies while interacting with their children during a shared storytelling activity. The main outcome measures included absolute change from baseline to final visit in the means for youth total number of story-related utterances, youth number of different word roots, and parent total number of story-related utterances.

Results

Significant increases in all primary outcome measures were observed in both treatment groups. Significant improvements were also observed in parent reports of the severity of spoken language and social impairments in both treatment groups. In all cases, the amount of change observed did not differ across the two treatment groups. Although gains in parental use of the PILI-targeted intervention strategies were observed in both treatment groups, parental use of the PILI strategies was correlated with youth gains in the placebo group and not in the lovastatin group.

Conclusion

Participants in both groups demonstrated significant changes in the primary outcome measures. The magnitude of change observed across the two groups was comparable, providing additional support for the efficacy of the use of PILI in youth with FXS.

Trial registration

US National Institutes of Health (ClinicalTrials.gov), NCT02642653. Registered 12/30/2015.
Overview of lower urinary tract symptoms post-trauma intensive care unit admission
Authors: Owusu Sekyere Emmanuel , Hardcastle Timothy Craig , Sathiram Ronisha , Tlou Boikhutso
Published: April 2020

Background

The study was undertaken to assess the incidence of lower urinary tract symptoms (LUTS) after short-term indwelling urethral catheter (IUC) in polytrauma patients admitted to a level one trauma unit using core lower urinary tract symptom score (CLSS). Data of patients admitted between January 2013 and December 2015 and meeting the study criteria were retrieved from the hospital informatics system. Chart review was done, and patients were subsequently interviewed telephonically.

Results

Ninety-four respondents comprising of 81.9% males and 18.1% females out of the 221 eligible patients were contacted. The most common LUTS reported was urethral pain, and 90% had mild to moderate symptoms. No severe LUTS were identified. There was a positive correlation between the duration of IUC and LUTS, but there was no statistically significant association between age and LUTS in our study population.

Conclusion

Short-term duration of IUC in the trauma ICU patient is associated with predominantly mild irritative LUTS which are mostly self-limiting and may not need further investigations and management. CLSS was found to be a useful screening tool. Further studies are needed to confirm findings in our study.
Epitherapy and immune checkpoint blockade: using epigenetic reinvigoration of exhausted and dysfunctional T cells to reimburse immunotherapy response
Authors: McGoverne Isabella , Dunn Jenny , Batham Jacob , Tu Wen Juan , Chrisp Jeremy , Rao Sudha
Published: April 2020

Background

Cancer cells subvert natural immunosuppression by upregulating the expression of checkpoint proteins and their ligands. For example, tumor cells expressing programmed death-ligand 1 (PD-L1) induce immune cell tolerance to cancers, thereby facilitating tumor progression. The recent clinical success of immunotherapy, particularly checkpoint blockade, represents a significant advance in cancer therapy. However, many cancers develop resistance to immunotherapies, and the underlying mechanisms and how these might be exploited to overcome resistance still need to be determined.

Methods

T cell dysfunction, in part caused by chronic T cell receptor stimulation, diminishes the capacity for durable responses to checkpoint blockade. Furthermore, T cell populations are phenotypically and functionally heterogeneous, resulting in varying responses to checkpoint blockade. Recent molecular studies of T cell heterogeneity have shown that checkpoint blockade on its own does not alter the epigenetic landscape of T cells, despite epigenetic changes governing T cell phenotype.

Conclusion

Here we argue that epigenetic modifiers can be used to prime and sensitize T cells to immunotherapy. Administering epitherapy in conjunction with checkpoint blockade could decrease T cell exhaustion and immunotherapy resistance in many cancer types.
Effect of continuous use of metformin on kidney function in diabetes patients with acute myocardial infarction undergoing primary percutaneous coronary intervention
Authors: Yu Qi , Zhu Jia-Jia , Liu Wen-Xian
Published: April 2020

Background

Diabetes patients presenting with ST-segment elevation myocardial infarction (STEMI) scheduled for primary percutaneous coronary intervention (PCI) have an increased risk of contrast induced-acute kidney injury (CI-AKI). The effects of continuous use of metformin on kidney function are still controversial in patients submitted to primary PCI. This study aimed to assess continuous metformin therapy on kidney function in diabetic patients undergoing coronary intervention.

Methods

Two hundred eighty-four patients with metformin-treated diabetes, who underwent coronary intervention within 24 h for STEMI, were enrolled in the retrospective study. All the patients had estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m2. According to the physicians’ decisions after admission, 119 patients continued metformin treatment after primary PCI, while 165 patients discontinued it > 48 h after the procedure. Serum creatinine was collected at admission and within 48 h post primary PCI to evaluate the incidence of CI-AKI. We performed a multiple logistic regression analysis to examine the determinants of CI-AKI.

Results

No statistical difference in CI-AKI incidence between the continuous and the discontinuous metformin group (12.6%vs10.3%, p = 0.545). Multivariable logistic regression analysis indicated eGFR ≤60 ml/min/1.73 m2[p = 0.025, OR: 3.131; 95% CI (1.156–8.482)] and contrast volume [p = 0.002, OR: 1.010; 95% CI (1.004–1.016)] were predictive factors of CI-AKI. Metformin therapy was irrelevant to CI-AKI [p = 0.365, OR: 0.698; 95% CI (0.320–1.521)]. No case of lactic acidosis was found in this study. Besides, the study supported discontinuation of metformin was not beneficial for patients’ blood glucose control after admission.

Conclusions

The study indicated that the metformin continuation after primary PCI for STEMI in diabetic patients with eGFR > 30 ml/min / 1.73 m2 did not increase the risk of CI-AKI.
Predicting MCI progression with FDG-PET and cognitive scores: a longitudinal study
Authors:   Alzheimer’ s Disease Neuroimaging Initiative (ADNI), Teng Lirong , Li Yongchao , Zhao Yu , Hu Tao , Zhang Zhe , Yao Zhijun , Hu Bin
Published: April 2020

Background

Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Studies on MCI progression are important for Alzheimer’s disease (AD) prevention. 18F fluoro-deoxy-glucose positron emission tomography (FDG-PET) has been proven to be a powerful tool for measuring cerebral glucose metabolism. In this study, we proposed a classification framework for MCI prediction with both baseline and multiple follow-up FDG-PET scans as well as cognitive scores of 33 progressive MCI (pMCI) patients and 46 stable MCI (sMCI) patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Method

First, PET images were normalized using the Yakushev normalization procedure and registered to the Brainnetome Atlas (BNA). The average metabolic intensities of brain regions were defined as static features. Dynamic features were the intensity variation between baseline and the other three time points and change ratios with the intensity obtained at baseline considered as reference. Mini-mental State Examination (MMSE) scores and Alzheimer’s disease Assessment Scale-Cognitive section (ADAS-cog) scores of each time point were collected as cognitive features. And F-score was applied for feature selection. Finally, support vector machine (SVM) with radial basis function (RBF) kernel was used for the three above features.

Results

Dynamic features showed the best classification performance in accuracy of 88.61% than static features (accuracy of 78.48%). And the combination of cognitive features and dynamic features improved the classification performance in specificity of 95.65% and Area Under Curve (AUC) of 0.9308.

Conclusion

Our results reported that dynamic features are more representative in longitudinal research for MCI prediction work. And dynamic features and cognitive scores complementarily enhance the classification performance in specificity and AUC. These findings may predict the disease course and clinical changes in individuals with mild cognitive impairment.
Waterpipe smoking among university students in Hong Kong: a cross-sectional study
Authors: Lee Jung Jae , Wu Yongda , Wang Man Ping , Yeung Karly Cheuk-Yin , Wong Janet Yuen-Ha , Smith Robert
Published: April 2020

Background

Waterpipe smoking has gained global popularity in recent years, especially among young people. However, there is a lack of empirical investigation into waterpipe smoking in East Asia. This study aimed to investigate the demographical and psycho-social characteristics and patterns of waterpipe smoking (WPS) among university students in Hong Kong.

Methods

A cross-sectional survey was conducted via online questionnaires administered to 1288 Hong Kong university students (mean age: 22.4 [SD = 3.8]). Logistic regressions were used to compute adjusted odd ratios (aOR) for waterpipe ever-smoking in relation to respondents’ characteristics. Moreover, multinomial logistic regression yielded adjusted RR (aRR) for four different smoking status (i.e., never, waterpipe-only, cigarette-only, and dual smoking) regarding the characteristics.

Results

23.8% of participants reported having ever smoked a waterpipe (vs. cigarette ever-smoking: 21.1%). Factors including being female (aOR:1.57; 95% CI: 1.22–2.02), older age (≥24 years: 4.17; 1.35–12.93), frequent alcohol consumption (>monthly: 26.02; 10.91–62.09), and higher sensation-seeking behaviours (high level: 2.98;1.46–6.08) were associated with waterpipe ever-smokers. The study also identified that demographical and psycho-social characteristics were variably associated with students’ smoking status. Particularly, more frequent alcohol consumption was most significantly associated with waterpipe-only smoking (aRR:45.73; 95% CI:11.44–182.73) (vs. cigarette-only smoking: 3.01; 1.76–5.14).

Conclusions

WPS is the most common form of tobacco smoking among university students in Hong Kong, and characteristics unique to the population were identified. There is no legislation of relevant policies on WPS despite its concerning significance in public health among young people, therefore immediate action to monitor and control WPS is needed in Hong Kong.
Central line bundle including split-septum device and single-use prefilled flushing syringes to prevent port-associated bloodstream infections: a cost and resource-utilization analysis
Authors: Devrim İlker , Özkul Mustafa Taha , Çağlar İlknur , Oruç Yeliz , Demiray Nevbahar , Tahta Neryal , Vergin Canan
Published: April 2020

Background

Central line bundle programs were found to be effective in decreasing central line-associated bloodstream infection rates in pediatric cancer patients with ports. However, cost-effectiveness studies of central line bundle programs in pediatric cancer patients are limited, and most available data are from intensive care unit or adult studies.

Methods

In this cross-sectional study spanning 6 years, comprehensive assessment of total health care costs attributable to CLABSI’s associated with ports between two periods.

Results

This cross-sectional study was carried out in the pediatric hematology-oncology ward of Dr. Behçet Uz Children’s Hospital from 1 August November 2011 to 31 July 2017. The CLABSI rates decreased significantly from 8.31 CLABSIs to 3.04 per 1000 central line days (p < 0.001). In the pre-bundle period, total attributable costs spent for of patients with CLABSI were $130,661, and in the bundle period, total attributable costs spent for patients with CLABSI were $116,579. Within bundle implantation, 71 potential CLABSI were prevented, which saved an additional $208,977.

Conclusion

Our study shows that central line bundles decreases not only the CLABSI rate but also decreases attributable costs due to CLABSI. Expenses spent for bundle elements, were covered by savings by preventing CLABSI with higher costs.
Scheduling medicines as controlled substances: addressing normative and democratic gaps through human rights-based analysis
Authors: Lohman Diederik , Barrett Damon
Published: April 2020

Recent years have seen contentious debate about efforts to schedule medicines such as ketamine and tramadol under the international drug control conventions. Proponents argue that misuse poses a significant risk to public health and that scheduling would help address these problems. However, scheduling of medicines can negatively affect their availability, accessibility and affordability for medical purposes, with serious health consequences for patients, especially in low and middle-income countries. The current process for scheduling medicines under the international drug control conventions does not provide sufficient normative standards through which balanced decisions may be reached. It is undemocratic in its structure and opaque in its reasoning. In this article, we argue that such decisions represent de facto limitations on the right to health and may engage the principle of non-retrogression. Using the examples of ketamine and tramadol, we propose that standard legal tests in international human rights law can help to address the normative and democratic deficits in the system and produce more rigorous, fairer and more transparent decisions.
Cytokine network analysis of immune responses before and after autologous dendritic cell and tumor cell vaccine immunotherapies in a randomized trial
Authors: Nistor Gabriel I. , Dillman Robert O.
Published: April 2020

Background

In a randomized phase II trial conducted in patients with metastatic melanoma, patient-specific autologous dendritic cell vaccines (DCV) were associated with longer survival than autologous tumor cell vaccines (TCV). Both vaccines presented antigens from cell-renewing autologous tumor cells. The current analysis was performed to better understand the immune responses induced by these vaccines, and their association with survival.

Methods

110 proteomic markers were measured at a week-0 baseline, 1 week before the first of 3 weekly vaccine injections, and at week-4, 1 week after the third injection. Data was presented as a deviation from normal controls. A two-component principal component (PC) statistical analysis and discriminant analysis were performed on this data set for all patients and for each treatment cohort.

Results

At baseline PC-1 contained 64.4% of the variance and included the majority of cytokines associated with Th1 and Th2 responses, which positively correlated with beta-2-microglobulin (B2M), programmed death protein-1 (PD-1) and transforming growth factor beta (TGFβ1). Results were similar at baseline for both treatment cohorts. After three injections, DCV-treated patients showed correlative grouping among Th1/Th17 cytokines on PC-1, with an inverse correlation with B2M, FAS, and IL-18, and correlations among immunoglobulins in PC-2. TCV-treated patients showed a positive correlation on PC-1 among most of the cytokines and tumor markers B2M and FAS receptor. There were also correlative changes of IL12p40 with both Th1 and Th2 cytokines and TGFβ1. Discriminant analysis provided additional evidence that DCV was associated with innate, Th1/Th17, and Th2 responses while TCV was only associated with innate and Th2 responses.

Conclusions

These analyses confirm that DCV induced a different immune response than that induced by TCV, and these immune responses were associated with improved survival.

Trial registrationClinical trials.gov NCT004936930 retrospectively registered 28 July 2009
Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model
Authors: Skuland Tonje , Låg Marit , Gutleb Arno C. , Brinchmann Bendik C. , Serchi Tommaso , Øvrevik Johan , Holme Jørn A. , Refsnes Magne
Published: April 2020

Background

Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression.

Results

Exposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments.

Conclusions

Si10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages.
Baby pangolins on my plate: possible lessons to learn from the COVID-19 pandemic
Authors: Volpato Gabriele , Fontefrancesco Michele F. , Gruppuso Paolo , Zocchi Dauro M. , Pieroni Andrea
Published: April 2020

The Journal of Ethnobiology and Ethnomedicine (JEET), throughout its 15 years of existence, has tried to provide a respected outlet for scientific knowledge concerning the inextricable links between human societies and nature, food, and health. Ethnobiology and ethnomedicine-centred research has moved at the (partially artificial and fictitious) interface between nature and culture and has investigated human consumption of wild foods and wild animals, as well as the use of wild animals or their parts for medicinal and other purposes, along with the associated knowledge, skills, practices, and beliefs. Little attention has been paid, however, to the complex interplay of social and cultural reasons behind the increasing pressure on wildlife. The available literature suggest that there are two main drivers that enhance the necessary conditions for infectious diseases to cross the species barrier from wild animals to humans: (1) the encroachment of human activities (e.g., logging, mining, agricultural expansion) into wild areas and forests and consequent ecological disruptions; and, connected to the former, (2) the commodification of wild animals (and natural resources in general) and an expanding demand and market for wild meat and live wild animals, particularly in tropical and sub-tropical areas. In particular, a crucial role may have been played by the bushmeat-euphoria and attached elitist gastronomies and conspicuous consumption phenomena. The COVID-19 pandemic will likely require ethnobiologists to reschedule research agendas and to envision new epistemological trajectories aimed at more effectively mitigating the mismanagement of natural resources that ultimately threats our and other beings’ existence.
Therapeutic management of severe hypothermia with veno-arterial ECMO: where do we stand? Case report and review of the current literature
Authors: Ledoux Aurélien , Saint Leger Piehr
Published: April 2020

Background

Severe accidental hypothermia is associated with high morbidity and mortality. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides an efficient rewarming method with complete cardiopulmonary support. The use of VA-ECMO for this indication has greatly improved the vital and functional prognosis of patients.

Case presentation

We report a case of a 46-year-old patient who was treated for severe hypothermia with a temperature of 22.4 °C along with initial cardiac arrest, whose progression was favorable after the implementation of VA-ECMO support. Two months after initial cardiac arrest, the patient was reassessed and showed signs of complete recovery with regard to his mental and physical capacities.

Conclusions

The recent international publications and groups of experts recommend the use of VA ECMO as the gold standard therapy to treat severe hypothermia. Therefore, it seems suitable to update the current knowledge on the topic by analysing the latest international publications. The performance of this technique calls into question ethical and economic factors. Two distinct medical teams tried to identify and regroup prognosis factors in predictive survival scores. They raise the question of the utility of these scores in clinical practice. Indeed, according to which survival rate should we proceed to prolonged resuscitation and implement VA-ECMO? Additional studies will be needed for external approval of these survival scores, and additional reflection by experts will be required.
The archaeal-bacterial lipid divide, could a distinct lateral proton route hold the answer?
Authors: Mencía Mario
Published: April 2020

The archaea-bacteria lipid divide is one of the big evolutionary enigmas concerning these two domains of life. In short, bacterial membranes are made of fatty-acid esters whereas archaeal ones contain isoprenoid ethers, though at present we do not have a good understanding on why they evolved differently. The lateral proton transfer mode of energy transduction in membranes posits that protons utilize the solvation layer of the membrane interface as the main route between proton pumps and ATPases, avoiding dissipation of energy to the bulk phase. In this article I present the hypothesis on a proton-transport route through the ester groups of bacterial phospholipids as an explanation for the evolutionary divergence seen between bacteria and archaea.

Reviewers

This article was reviewed by Uri Gophna (Editorial Board member) and Víctor Sojo.
Can direct smear results that are routinely collected at health centre level be used for monitoring the impact of mass drug administration with praziquantel on schistosomiasis in Burundi? A preliminary assessment
Authors: Bizimana Paul , Polman Katja , Ortu Giuseppina , Krit Meryam , Nsabiyumva Frédéric , Nkeshimana Audace , Bijabuka Urlich , Nibakire Marcelline , Van Geertruyden Jean-Pierre
Published: April 2020

Background

Intestinal schistosomiasis is still a public health problem in Burundi. Since 2008, annual mass drug administration with praziquantel has been rolled out in 11 endemic districts. The national programme relies on school-based surveys with kato-katz to monitor the impact of mass drug administration. We explored whether routine data on intestinal schistosomiasis as determined by direct fecal smears at health centre level could be used.

Methods

From the Burundian National Health Information System, we collected routine incidence data on intestinal schistosomiasis as determined by direct smear examination in all 45 sanitary districts during 2011–2015. A temporal trends analysis was performed using a mixed negative binomial regression. Sanitary districts with mass drug administration campaigns with praziquantel (n = 11) were compared with those without (n = 34). In addition, prevalence data on intestinal schistosomiasis based on kato-katz results from a school-based national mapping in 2014 were compared with the incidence data in health centres based on direct smear results, in the same 45 sanitary districts.

Results

In the 11 sanitary districts applying mass drug administration with praziquantel, the incidence rate decreased significantly for the years 2014 (β2014 = − 0.826, P = 0.010) and 2015 (β2015 = − 1.294, P < 0.001) and for the five-year period (β = − 0.286, P < 0.001), whereas in the 34 districts where mass drug administration was not delivered, there was no significant decrease over time (β = − 0.087, P = 0.219). In most of the 45 sanitary districts, the low prevalence based on kato-katz in school children was confirmed by low incidence rates based on direct smears in the health centres.

Conclusions

National Health Information System surveillance data, based on routinely collected direct smear results at health centre level, may be able to monitor the impact of mass drug administration with praziquantel on intestinal schistosomiasis in Burundi. Control and elimination of intestinal schistosomiasis call for integration of adequate diagnosis and treatment into routine activities of primary health care facilities, as recommended by the World Health Organization since more than 20 years. When moving towards elimination, more sensitive tests, such as the point-of-care circulating cathodic antigen assay are desirable.
The effects of dog management on Echinococcus spp. prevalence in villages on the eastern Tibetan Plateau, China
Authors: Weng Xiaodong , Mu Zhiqiang , Wei Xu , Wang Xu , Zuo Qingqiu , Ma Shuo , Ding Youzhong , Wang Xiaoming , Wu Weiping , Craig Philip S. , Wang Zhenghuan
Published: April 2020

Background

The pastoral area of the eastern Tibetan Plateau is highly endemic for human echinococcosis. Domestic dogs are the main definitive host for the transmission of both Echinococcus granulosus (sensu lato) and E. multilocularis to humans. To control the infection risks, a national-level canine echinococcosis prevention and control programme has been implemented since 2015 in Shiqu County, Ganze Tibetan Autonomous Prefecture, Sichuan, China. The objective of this study was to evaluate its effect on Echinococcus spp. prevalence in dogs.

Methods

We surveyed 69 households with 84 owned dogs, for dog fecal samples and dog keeping information in the villages of Rizha and Eduoma. A total of 105 dog fecal samples (75 from owned dogs and 30 unknown dog fecal samples) were collected between 2015–2017 to determine Echinococcus spp. prevalence using copro-PCR. Eight variables based on household surveys were included into a logistic regression model for significant risk factors to canine echinococcosis prevalence in dogs.

Results

Between 2015–2017, the overall Echinococcus spp. copro-DNA prevalence decreased significantly in dogs from 51.2% (2015) to 20.0% (2017) in Rizha, and insignificantly from 11.5% (2016) to 4.3% (2017) in Eduoma. Echinococcus multilocularis was the most prevalent species continually copro-DNA detected during the entire study period, while E. granulosus was rare and not detected in 2017. Echinococcus shiquicus copro-DNA prevalence (a probable non-zoonotic wildlife species) was as high in dogs as that of E. multilocularis, although only detected in 2015 in Rizha. Unleashed dog feces were mainly collected in Rizha in 2015. Although 93.2% of owned dogs were leashed, and the monthly praziquantel dosing rate reached 97%, E. multilocularis infection could still be detected in 11.1% of owned dogs in 2017. Monthly deworming, leashing dogs 24 h per day, and the avoidance of dogs feeding on livestock viscera were significant measures to prevent canine echinococcosis infection in owned dogs.

Conclusions

Carrying out a canine echinococcosis prevention and control programme can significantly decrease Echinococcus spp. prevalence. The potential contact between leashed dogs and wild small mammals is still a risk for re-infection of owned dogs with E. multilocularis. This study shows that the long-term application of regular dog treatment with praziquantel in the vast and remote echinococcosis endemic areas of the eastern Tibetan Plateau can reduce transmission in dogs but remains a challenging intervention.
Paternity seven years after a negative post-vasectomy semen analysis: a case report
Authors: Michaelides Athena , Ghani Mehrban
Published: April 2020

Background

Vasectomy is one of the permanent methods of contraception; however, the risk of conception still exists. Early failure, defined as a postoperative semen analysis showing persistent motile sperm, occurs in 1 in every 250 patients. Late failure, defined as the rejoining of the severed ends of the vas deferens, occurs in 1 in every 2000 patients.

Case presentation

A healthy 37-year-old British male presented to our clinic because his wife had conceived seven years after he had undergone a vasectomy. The result of his semen analysis after the vasectomy was negative, and the histopathological report confirmed that the sample contained tissue from both the left and right vas deferens. His wife conceived seven years after the procedure, and semen analysis at that time confirmed a total of 0.5 million sperm per milliliter of semen in a total semen sample of 6.3 ml. The total number of motile sperm recorded was 2.5 million.

Conclusion

This case shows that late recanalization can occur up to seven years after a vasectomy. Patients should be informed prior to the procedure that late recanalization, although rare, may still occur. Post-vasectomy paternity necessitates further counseling to ensure that the patient and the patient’s partner fully understand the implications and options available to them.
Common gene expression signatures in Parkinson’s disease are driven by changes in cell composition
Authors: Nido Gonzalo S. , Dick Fiona , Toker Lilah , Petersen Kjell , Alves Guido , Tysnes Ole-Bjørn , Jonassen Inge , Haugarvoll Kristoffer , Tzoulis Charalampos
Published: April 2020

The etiology of Parkinson’s disease is largely unknown. Genome-wide transcriptomic studies in bulk brain tissue have identified several molecular signatures associated with the disease. While these studies have the potential to shed light into the pathogenesis of Parkinson’s disease, they are also limited by two major confounders: RNA post-mortem degradation and heterogeneous cell type composition of bulk tissue samples. We performed RNA sequencing following ribosomal RNA depletion in the prefrontal cortex of 49 individuals from two independent case-control cohorts. Using cell type specific markers, we estimated the cell type composition for each sample and included this in our analysis models to compensate for the variation in cell type proportions. Ribosomal RNA depletion followed by capture by random primers resulted in substantially more even transcript coverage, compared to poly(A) capture, in post-mortem tissue. Moreover, we show that cell type composition is a major confounder of differential gene expression analysis in the Parkinson’s disease brain. Accounting for cell type proportions attenuated numerous transcriptomic signatures that have been previously associated with Parkinson’s disease, including vesicle trafficking, synaptic transmission, immune and mitochondrial function. Conversely, pathways related to endoplasmic reticulum, lipid oxidation and unfolded protein response were strengthened and surface as the top differential gene expression signatures in the Parkinson’s disease prefrontal cortex. Our results indicate that differential gene expression signatures in Parkinson’s disease bulk brain tissue are significantly confounded by underlying differences in cell type composition. Modeling cell type heterogeneity is crucial in order to unveil transcriptomic signatures that represent regulatory changes in the Parkinson’s disease brain and are, therefore, more likely to be associated with underlying disease mechanisms.