bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons from a training needs assessment to strengthen the capacity of routine immunization service providers in Nigeria
Authors: Arogundade Linda , Akinwumi Titilola , Molemodile Shola , Nwaononiwu Ebubechi , Ezika Joshua , Yau Inuwa , Wonodi Chizoba
Published: September 2019

Background

Health workers (HWs) providing routine immunization (RI) services play a crucial role in influencing vaccine uptake, a key determinant of improved immunization coverage. Over the years, Training Needs Assessments (TNAs) have not been routinely utilized in Nigeria to determine unmet needs of health workers offering immunization services and what approaches should be adopted to meet their training needs. The objective was to assess the level of Expanded Program on Immunization (EPI) knowledge among RI service providers and tutors in pre-service institutions in three Nigerian states, to identify unfulfilled training needs and their implications. It also sought HWs perception on a pilot training approach, where tutors will be used for in-service training.

Methods

TNA survey tools were designed to obtain knowledge-based information on the fundamental EPI concepts through key informant interviews and focus group discussions with 90 HWs and 27 pre-service tutors. Quantitative data was also obtained, hence utilizing a mixed method approach for the study.

Results

In spite of several previous trainings, HWs knowledge on basic immunization concepts including Reaching Every Ward (REW) strategy was varied and suboptimal. 83% of the HWs could not differentiate between the live attenuated and killed vaccines. In addition, pre-service tutors knowledge of fundamental EPI concepts, as well as HW perception of the new training approach also varied across the states.

Conclusion

TNAs are valuable in determining specific training approaches to improve HWs skills needed to implement strategies required to increase vaccine uptake. However, EPI managers must be mindful of contextual factors beyond training needs such as finance and security, that can affect HW performance.
Determination of reliable lung function parameters in intubated mice
Authors: Bonnardel Eline , Prevel Renaud , Campagnac Marilyne , Dubreuil Marielle , Marthan Roger , Berger Patrick , Dupin Isabelle
Published: September 2019

Background

Animal models and, in particular, mice models, are important tools to investigate the pathogenesis of respiratory diseases and to test potential new therapeutic drugs. Lung function measurement is a key step in such investigation. In mice, it is usually performed using forced oscillation technique (FOT), negative pressure-driven forced expiratory (NPFE) and pressure-volume (PV) curve maneuvers. However, these techniques require a tracheostomy, which therefore only allows end-point measurements. Orotracheal intubation has been reported to be feasible and to give reproducible lung function measurements, but the agreement between intubation and tracheostomy generated-data remains to be tested.

Methods

Using the Flexivent system, we measured lung function parameters (in particular, forced vital capacity (FVC), forced expiratory volume in the first 0.1 s (FEV0.1), compliance (Crs) of the respiratory system, compliance (C) measured using PV loop and an estimate of inspiratory capacity (A)) in healthy intubated BALB/cJ mice and C57BL/6 J mice and compared the results with similar measurements performed in the same mice subsequently tracheostomized after intubation, by means of paired comparison method, correlation and Bland-Altman analysis. The feasibility of repetitive lung function measurements by intubation was also tested.

Results

We identified parameters that are accurately evaluated in intubated animals (i.e., FVC, FEV0.1, Crs, C and A in BALB/cJ and FVC, FEV0.1, and A in C57BL/6 J). Repetitive lung function measurements were obtained in C57BL/6 J mice.

Conclusion

This subset of lung function parameters in orotracheally intubated mice is reliable, thereby allowing relevant longitudinal studies.
Reduction of malaria vector mosquitoes in a large-scale intervention trial in rural Burkina Faso using Bti based larval source management
Authors: Dambach Peter , Baernighausen Till , Traoré Issouf , Ouedraogo Saidou , Sié Ali , Sauerborn Rainer , Becker Norbert , Louis Valérie R.
Published: September 2019

Background

Malaria remains one of the most important causes of morbidity and death in sub-Saharan Africa. Along with early diagnosis and treatment of malaria cases and intermittent preventive treatment in pregnancy (IPTp), vector control is an important tool in the reduction of new cases. Alongside the use of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), targeting the vector larvae with biological larvicides, such as Bacillus thuringiensis israelensis (Bti) is gaining importance as a means of reducing the number of mosquito larvae before they emerge to their adult stage. This study presents data corroborating the entomological impact of such an intervention in a rural African environment.

Methods

The study extended over 2 years and researched the impact of biological larviciding with Bti on malaria mosquitoes that were caught indoors and outdoors of houses using light traps. The achieved reductions in female Anopheles mosquitoes were calculated for two different larviciding choices using a regression model.

Results

In villages that received selective treatment of the most productive breeding sites, the number of female Anopheles spp. dropped by 61% (95% CI 54–66%) compared to the pre-intervention period. In villages in which all breeding sites were treated, the number of female Anopheles spp. was reduced by 70% (95% CI 64–74%) compared to the pre-intervention period.

Conclusion

It was shown that malaria vector abundance can be dramatically reduced through larviciding of breeding habitats and that, in many geographical settings, they are a viable addition to current malaria control measures.
Ethics, health policy-making and the economic crisis: a qualitative interview study with European policy-makers
Authors: Brall Caroline , Schröder-Bäck Peter , Porz Rouven , Tahzib Farhang , Brand Helmut
Published: September 2019

Background

The economic crisis posed various challenges to policy-makers who had to decide on which health policy measures to focus on and on which to refrain from. The aim of this research was to assess the relevance of ethics and to highlight ethical dimensions in decision-taking by policy-makers with regard to policy and priority-setting in health systems posed by the economic crisis.

Methods

Semi-structured qualitative interviews were conducted with eight European policy-makers from six countries.

Results

All interviewees recalled difficult and strenuous situations where they had to prioritise between distinct areas to focus on and invest in, for example around choices between prioritising medications, health professional staffing, care specific equipment, or urgent infrastructure issues. Values could be identified which they deemed as important within the policy-making process, such as trust and responsibility. They explicitly expressed the need for ethical tools and assistance in terms of policy advice for reaching morally sustainable decisions in health policy matters.

Conclusions

The study showed that ethical concepts and values frequently come into play in health policy-making, and that ethics is highly relevant in policy-makers’ daily decision-taking, yet that they lack ethical guidance on what to base their decisions. The study is of relevance since it can provide future decisions on austerity-related issues with an ethical underpinning and could identify areas of moral concern.
Molecular characterization and clinical relevance of m6A regulators across 33 cancer types
Authors: Li Yongsheng , Xiao Jun , Bai Jing , Tian Yi , Qu Yinwei , Chen Xiang , Wang Qi , Li Xinhui , Zhang Yunpeng , Xu Juan
Published: September 2019

The methylation of N6 adenosine (m6A) plays a critical role in diverse biological processes. However, knowledge regarding the reconstitution of m6A across cancer types is still lacking. Here, we systematically analyzed the molecular alterations and clinical relevance of m6A regulators across > 10,000 subjects representing 33 cancer types. We found that there are widespread genetic alterations to m6A regulators, and that their expression levels are significantly correlated with the activity of cancer hallmark-related pathways. Moreover, m6A regulators were found to be potentially useful for prognostic stratification, and we identified IGF2BP3 as a potential oncogene across multiple cancer types. Our results provide a valuable resource that will guide both mechanistic and therapeutic analyses of the role of m6A regulators in cancer.
Correlates and determinants of Early Infant Diagnosis outcomes in North-Central Nigeria
Authors: Dakum Patrick , Tola Monday , Iboro Nta , Okolo Chukwuemeka A. , Anuforom Olachi , Chime Christopher , Peters Sam , Jumare Jibreel , Ogbanufe Obinna , Ahmad Aliyu , Ndembi Nicaise
Published: September 2019

Background

A negative status following confirmatory Early Infant Diagnosis (EID) is the desired pediatric outcome of prevention of Mother to Child Transmission (PMTCT) programs. EID impacts epidemic control by confirming non-infected HIV-exposed infants (HEIs) and prompting timely initiation of ART in HIV-infected babies which improves treatment outcomes.

Objectives

We explored factors associated with EID outcomes among HEI in North-Central Nigeria.

Method

This is a cross-sectional study using EID data of PMTCT-enrollees matched with results of HEI’s dried blood samples (DBS), processed for DNA-PCR from January 2015 through July 2017. Statistical analyses were done using SPSS version 20.0 to generate frequencies and examine associations, including binomial logistic regression with p < 0.05 being statistically significant.

Results

Of 14,448 HEI in this analysis, 51.8% were female and 95% (n = 12,801) were breastfed. The median age of the infants at sample collection was 8 weeks (IQR 6–20), compared to HEI tested after 20 weeks of age, those tested earlier had significantly greater odds of a negative HIV result (≤ 6 weeks: OR = 3.8; 6–8 weeks: OR = 2.1; 8–20 weeks: OR = 1.5) with evidence of a significant linear trend (p < 0.001). Similarly, HEI whose mothers received combination antiretroviral therapy (cART) before (OR = 11.8) or during the index pregnancy (OR = 8.4) had significantly higher odds as compared to those whose mothers did not receive cART. In addition, HEI not breastfed had greater odds of negative HIV result as compared to those breastfed (OR = 1.9).

Conclusions

cART prior to and during pregnancy, earlier age of HEI at EID testing and alternative feeding other than breastfeeding were associated with an increased likelihood of being HIV-negative on EID. Therefore, strategies to scale-up PMTCT services are needed to mitigate the burden of HIV among children.
Neuromuscular adaptations and sensorimotor integration following a unilateral transfemoral amputation
Authors: Claret Claudia Ramos , Herget Georg W. , Kouba Lukas , Wiest Daniel , Adler Jochen , von Tscharner Vinzenz , Stieglitz Thomas , Pasluosta Cristian
Published: September 2019

Background

Following an amputation, the human postural control system develops neuromuscular adaptations to regain an effective postural control. We investigated the compensatory mechanisms behind these adaptations and how sensorimotor integration is affected after a lower-limb transfemoral amputation.

Methods

Center of pressure (CoP) data of 12 unilateral transfemoral amputees and 12 age-matched able-bodied subjects were recorded during quiet standing with eyes open (EO) and closed (EC). CoP adjustments under each leg were recorded to study their contribution to posture control. The spatial structure of the CoP displacements was characterized by measuring the mean distance, the mean velocity of the CoP adjustments, and the sway area. The Entropic Half-Life (EnHL) quantifies the temporal structure of the CoP adjustments and was used to infer disrupted sensory feedback loops in amputees. We expanded the analysis with measures of weight-bearing imbalance and asymmetry, and with two standardized balance assessments, the Berg Balance Scale (BBS) and Timed Up-and-Go (TUG).

Results

There was no difference in the EnHL values of amputees and controls when combining the contributions of both limbs (p = 0.754). However, amputees presented significant differences between the EnHL values of the intact and prosthetic limb (p <  0.001). Suppressing vision reduced the EnHL values of the intact (p = 0.001) and both legs (p = 0.028), but not in controls. Vision feedback in amputees also had a significant effect (increase) on the mean CoP distance (p <  0.001), CoP velocity (p <  0.001) and sway area (p = 0.007). Amputees presented an asymmetrical stance. The EnHL values of the intact limb in amputees were positively correlated to the BBS scores (EO: ρ = 0.43, EC: ρ = 0.44) and negatively correlated to the TUG times (EO: ρ = − 0.59, EC: ρ = − 0.69).

Conclusion

These results suggest that besides the asymmetry in load distribution, there exist neuromuscular adaptations after an amputation, possibly related to the loss of sensory feedback and an altered sensorimotor integration. The EnHL values suggest that the somatosensory system predominates in the control of the intact leg. Further, suppressing the visual system caused instability in amputees, but had a minimal impact on the CoP dynamics of controls. These findings points toward the importance of providing somatosensory feedback in lower-limb prosthesis to reestablish a normal postural control.

Trial registration

DRKS00015254, registered on September 20th, 2018.
Humanism influencing the organization of the health care system and the ethics of medical relations in the society of Bosnia-Herzegovina
Authors: Kvesić Ante , Galić Kristina , Vukojević Mladenka
Published: September 2019

Every successful health care system should be based on some general humanistic ideals. However, the nationally organized health care systems of most European countries usually suffer from a deficiency in common ethical values based on universal human principles. When transitional societies, such as that of Bosnia-Herzegovina are concerned, health care organizational models are even more dysfunctional. The sources of a dysfunction in medical care system of Bosnia-Herzegovina are manifold and mutually controversial, including a lack of shared principles, an inappropriate involvement of politicians in medical care and practice, administrative difficulties arising from superficial communication systems, as well as economic limits concerned with the financing of health care. The deficiency of a moral culture of medicine, which is correlated to a general collapse of morality is also responsible for many problems affecting various aspects of life including medical care. Hence, medical ethics from a virtue perspective is becoming an important ingredient of any improvement deigned to provide better-quality medical care.

The aim of this paper is to underline the influence of humanism on the organization of health care systems and the ethics of medical interrelations in the society of Bosnia-Herzegovina. It is not intended to diagnose or resolve the problems, but to analyze them. It is also a critique of specific socio-political-economic influences on this health care system, inquiring if well-educated individuals in the virtues, which are involved in medical practice and education, would counteract them.

In conclusion, humanism creates a universal ethical structure, which is based on human values such as fidelity, trust, benevolence, intellectual honesty, courage, compassion and truthfulness. These values should represent the standard around which medical care is organized. Since the health care system in Bosnia-Herzegovina is not entirely founded upon humanistic ideals, addressing the socio-political-economic conditions that constantly undermine those values is a prerequisite for any much-needed improvements of the medical care.
Whole brain radiation therapy does not improve the overall survival of EGFR-mutant NSCLC patients with leptomeningeal metastasis
Authors: Yan Weiwei , Liu Yang , Li Ji , Han Anqin , Kong Li , Yu Jinming , Zhu Hui
Published: September 2019

Background

Leptomeningeal metastasis (LM) is a devastating and terminal complication of advanced non-small-cell lung cancer (NSCLC), especially in patients harboring epidermal growth factor receptor (EGFR) mutations. The role of whole brain radiation therapy (WBRT) in the treatment of EGFR-mutant NSCLC patients with LM is not conclusive. Therefore, we conducted a retrospective study to evaluate the therapeutic effect of WBRT in this setting.

Methods

EGFR-mutant NSCLC patients with LM, who had previously received treatment at the Shandong Cancer Hospital and Institute from July 2014 to March 2018 were reviewed retrospectively. LM was diagnosed by positive CSF cytology and/or leptomeningeal-enhanced magnetic resonance imaging (MRI). Survival was estimated using the Kaplan-Meier method.

Results

In total, 51 EGFR-mutated NSCLC patients with LM were eligible for analysis, subdivided into 26 in the WBRT group and 25 in the non-WBRT group. No significant differences were observed in intracranial ORR (15.4% vs. 16%, p = 0.952) and DCR (34.7% vs. 28%, p = 0.611) between the two groups. The median iPFSLM and OSLM for the entire cohort were 3.3 months (95% CI: 2.77–3.83) and 12.6 months (95% CI: 9.66–15.54), respectively. No difference in iPFSLM was observed between the WBRT and non-WBRT groups (median 3.9 vs. 2.8 months; HR = 0.506, p = 0.052). The median OSLM was 13.6 months in the WBRT group, compared with 5.7 months in the non-WBRT group (HR = 0.454, p = 0.022). Multivariate analyses of OSLM showed that KPS ≥ 80 at the time of LM diagnosis (HR = 0.428, 95% CI: 0.19–0.94; p = 0.034) and the administration of EGFR-TKIs (HR = 0.258, 95% CI: 0.11–0.58; p = 0.001) were independent predictors of survival, but WBRT (HR = 0.49, 95% CI: 0.24–1.01; p = 0.54) was not. Toxicities associated with WBRT or other treatment were rare.

Conclusion

For EGFR-mutated NSCLC patients with LM, WBRT did not improve intracranial treatment response and survival statistically.
Effect of different geometrical structure of scapula on functional recovery after shoulder arthroscopy operation
Authors: Shi Xuchao , Xu Yuanlin , Dai Bo , Li Weilong , He Zhennian
Published: September 2019

Background

There are no published studies of the influence of geometry of the scapula on the postoperative recovery of rotator cuff injuries. Our aim was to explore the relationship between the critical shoulder angle (CSA), acromion index (AI), glenoid inclination (GI), and postoperative repair outcomes in shoulder joints after arthroscopic supraspinatus tendon repair.

Methods

Sixty two patients suffering a supraspinatus tear were analyzed retrospectively following failure of conservative treatment and subsequent shoulder arthroscopy in our hospital. Standard anterior and posterior X-rays of the injured shoulder had been performed prior to surgery, with follow ups for at least 2 years (24–43 months). Magnetic resonance imaging (MRI) was performed 2 years after surgery to assess repair of the supraspinatus tendon. Patients were divided into either the intact or re-tear group, according to the MRI results. In addition, assessments using the Constant Shoulder Score (CSS), the American Shoulder and Elbow Surgeon (ASES) Shoulder Assessment Form, the University of California at Los Angeles (UCLA) score and visual analog scale (VAS) score were performed to establish shoulder function at the 2-year evaluation for each patient.

Results

The mean CSA of all patients was 35.79° ± 3.59°, mean AI was 0.72 ± 0.05, and mean GI was 15.87° ± 3.62°. The CSA, AI, and GI in the intact group were statistically significantly different than the re-tear group (p < 0.05). There was no correlation between the magnitude of the CSA, AI, or GI and any shoulder function score (p > 0.05).

Conclusions

The geometry of the scapula had no significant effect on the recovery of postoperative function of patients with rotator cuff injury, but the value of the CSA, AI, and GI affected the risk of rotator cuff re-tear.
Heart valve operations associated with reduced risk of death from mitral valve disease but other operations associated with increased risk of death: a national population-based case–control study
Authors: Li Ruo-Ling , Luo Ci-Wen , Ho Yung-Chyuan , Lee Shiuan-Shinn , Kuan Yu-Hsiang
Published: September 2019

Background

Mitral valve disease is the most common heart valve disease worldwide. Heart valve operation is the predominant treatment strategy for heart valve disease. This study analyzed the death risk from heart valve disease with respect to the frequency of heart valve operation and other operations in patients with mitral valve disease.

Materials and methods

We conducted a retrospective nationwide population-based case–control study using a claims dataset from Taiwan’s National Health Insurance Research Database. The case and control groups enrolled mitral valve disease patients from 2002 to 2013 who had either underwent an heart valve operation procedure or not, respectively. Conditional logistic regression was estimated the odds ratios (ORs) associated with various risk factors for heart valve operation-related death, including other operations and comorbidities.

Results

A total of 25,964 patients with mitral valve disease were recruited for the study and divided into heart valve operation (600 patients) and non-heart valve operation (25,364 patients) groups. After matching, a total of 1800 non-heart valve operation patients were selected for final analysis. Heart valve operation was associated with decreased risk of death (adjusted OR [aOR] 0.439), but operations related to other cardiovascular disease (CVD, aOR 3.691), respiratory conditions (aOR 3.210), and the urinary system (aOR 1.925) were associated with increased risk of death for patients with mitral valve disease. Patients with mitral valve disease and diabetes (aOR 1.505), chronic kidney disease (CKD, aOR 3.760), or emphysema (aOR 2.623) also had a higher risk of death. Patients who underwent more heart valve operations had a lower risk of death from mitral valve disease, but patients who underwent more other operations had a higher risk of death from mitral valve disease.

Conclusions

The death risk for patients with mitral valve disease patients could be lowered by more frequently performing heart valve operations. However, the risk of death is increased for patients with mitral valve disease who more frequently undergo other operations, chiefly those for other CVD system, respiratory conditions, and urinary system, or have comorbidities such as diabetes, chronic kidney disease, and emphysema.
Overall intact cognitive function in male X-linked adrenoleukodystrophy adults with normal MRI
Authors: Buermans Noortje J. M. L. , van den Bosch Sharon J. G. , Huffnagel Irene C. , Steenweg Marjan E. , Engelen Marc , Oostrom Kim J. , Geurtsen Gert J.
Published: September 2019

Background

Men with the hereditary peroxisomal disorder X-linked adrenoleukodystrophy (ALD) are at risk of developing inflammatory demyelinating lesions in the brain. In the absence of inflammatory (post-contrast enhancing) lesions on MRI cognitive function is considered spared, but some form of cognitive dysfunction may nevertheless be present. The aim of this cross-sectional study was to characterize cognitive functioning of ALD men with no or minimal MRI abnormalities, which will define cognitive functioning in this category of patients.

Methods

A neuropsychological battery covering a broad range of cognitive domains, including language, verbal and non-verbal memory, visuoconstruction, executive functioning, and psychomotor speed, was used. Means and proportions of borderline and impaired T scores ≤36 were compared to the standardized norm group and a qualitative case-by-case analysis was performed for participants with T scores ≤36 within ≥2 domains. Patients with MRI abnormalities that were extensive (Loes score > 3) or showed enhancement post-contrast were excluded.

Results

Thirty-three men participated (median age 44 years, range 19–71). Mean performance on verbal fluency was poorer in patients (45.70 ± 8.85 patients vs. 50 ± 10 standardized norm group, p = 0.009), as was the percentage of borderline and impaired scores on visuoconstruction (Beery VMI: 19% patients vs. 8% standardized norm group, p = 0.02; RCFT copy: 81% patients vs. 2% standardized norm group, p < 0.0005) and mental reaction time during a complex decision task (18% patients vs. 8% standardized norm group, p = 0.055). Moreover, 9/33 (27.3%) patients had T scores ≤36 within ≥2 domains.

Conclusions

Given the heterogeneous pattern of mostly borderline scores cognitive functioning seems not impaired in the vast majority of adult ALD males with no or minimal MRI abnormalities. However, borderline to impaired cognitive dysfunction was present in 27.3%, with the majority being borderline scores. Longitudinal studies will have to determine if this reflects early cerebral disease under the detection limit of MRI.
Australian R U OK?Day campaign: improving helping beliefs, intentions and behaviours
Authors: Ross Anna M. , Bassilios Bridget
Published: September 2019

Background

Suicide is a major public health concern and has been recognised as a public health priority. R U OK?Day aims to prevent suicide by encouraging and empowering Australians to reach out to friends and family who might be experiencing personal difficulties. This study aims to update the evaluation of the public awareness campaign ‘R U OK?Day’ that was conducted using 2014 data.

Methods

Data from 2013 participants were collected via an online survey following the R U OK?Day campaign implemented in 2017. Outcome measures included campaign awareness and participation, past 12-month help-seeking, helping beliefs, helping intentions and helping behaviours. Data were analysed using z-tests, Chi square and regression analyses in SPSS.

Results

Both campaign awareness and participation have increased since 2014, from 66% and 19% to 78% and 32%. Campaign exposure was associated with stronger beliefs in the importance and the ease of asking “Are you okay?”, and increased the likelihood of intentions to use recommended helping actions by two to three times compared to those not exposed to the campaign. Participants who were exposed to the R U OK?Day campaign were up to six times more likely to reach out to someone who might be experiencing personal difficulties compared to those not exposed to the campaign. Interestingly, those who had sought help from a mental health professional in the past 12 months were more likely to be aware of, and participate in, the campaign, suggesting people experiencing mental health issues recognise the value of seeking—and giving—social support.

Conclusions

The R U OK?Day campaign continues to be relevant and effective in spreading key messages about the importance of reaching out to others and empowering members of the community to have conversations about life problems. The campaign’s impact is increasing over time through increased campaign awareness and participation, and improving helping beliefs, intentions and behaviours. Ongoing monitoring and evaluation of the campaign’s impact is vital and may inform potential changes needed to further enhance its impact.
Omega-3 fatty acids for the treatment of depressive disorders in children and adolescents: a meta-analysis of randomized placebo-controlled trials
Authors: Zhang Li , Liu Huan , Kuang Li , Meng Huaqing , Zhou Xinyu
Published: September 2019

Background

To investigate the efficacy and safety of omega-3 fatty acids (O3FA) in treating depressive disorders in children and adolescents.

Method

We conducted a comprehensive search in electronic databases and hand-searched articles included for relevant studies. We included randomized controlled trials which studied on O3FA for treatment of children and adolescents with depression. The standard mean differences (SMDs) and the odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by a random-effects model. The primary outcomes were end-point depressive symptoms scores (efficacy) and all-cause discontinuation (safety). The secondary outcome of response rate was also assessed. Subgroup analyses were performed by age, severity of depression and dosage. Risk of bias assessment was performed based on the Jadad score and the Cochrane Collaboration’s risk-of-bias method.

Results

A total of four studies with 153 participants were included. In terms of efficacy, there was no significant difference of end-point depressive symptoms scores between O3FA and placebo (SMD = − 0.12, 95% CI − 0.53 to 0.30, P = 0.58;I2= 30%). In terms of safety, the all-cause discontinuation showed no statistical significance between O3FA and placebo (OR = 1.3, 95% CI 0.58 to 2.93, P = 0.53;I2= 0%). The response rate of O3FA was also not significant better than that of placebo (OR = 1.57, 95% CI 0.26 to 9.39, P = 0.62;I2= 71%). Besides, there were also no significant differences in those subgroup analyses outcomes. The risk of bias of included trials were not high.

Conclusions

Only considering the limited evidence of O3FA in the acute treatment of major depressive disorder, it did not seem to offer a clear advantage for children and adolescents.
TCR-like antibodies in cancer immunotherapy
Authors: He Qinghua , Liu Zhaoyu , Liu Zhihua , Lai Yuxiong , Zhou Xinke , Weng Jinsheng
Published: September 2019

Cancer immunotherapy has been regarded as the most significant scientific breakthrough of 2013, and antibody therapy is at the core of this breakthrough. Despite significant success achieved in recent years, it is still difficult to target intracellular antigens of tumor cells with traditional antibodies, and novel therapeutic strategies are needed. T cell receptor (TCR)-like antibodies comprise a novel family of antibodies that can recognize peptide/MHC complexes on tumor cell surfaces. TCR-like antibodies can execute specific and significant anti-tumor immunity through several distinct molecular mechanisms, and the success of this type of antibody therapy in melanoma, leukemia, and breast, colon, and prostate tumor models has excited researchers in the immunotherapy field. Here, we summarize the generation strategy, function, and molecular mechanisms of TCR-like antibodies described in publications, focusing on the most significant discoveries.
Cryptosporidium infections in terrestrial ungulates with focus on livestock: a systematic review and meta-analysis
Authors: Hatam-Nahavandi Kareem , Ahmadpour Ehsan , Carmena David , Spotin Adel , Bangoura Berit , Xiao Lihua
Published: September 2019

Background

Cryptosporidium spp. are causative agents of gastrointestinal diseases in a wide variety of vertebrate hosts. Mortality resulting from the disease is low in livestock, although severe cryptosporidiosis has been associated with fatality in young animals.

Methods

The goal of this systematic review and meta-analysis was to review the prevalence and molecular data on Cryptosporidium infections in selected terrestrial domestic and wild ungulates of the families Bovidae (bison, buffalo, cattle, goat, impala, mouflon sheep, sheep, yak), Cervidae (red deer, roe deer, white-tailed deer), Camelidae (alpaca, camel), Suidae (boar, pig), Giraffidae (giraffes) and Equidae (horses). Data collection was carried out using PubMed, Scopus, Science Direct and Cochran databases, with 429 papers being included in this systematic analysis.

Results

The results show that overall 18.9% of ungulates from the investigated species were infected with Cryptosporidium spp. Considering livestock species (cattle, sheep, goats, pigs, horses and buffaloes), analysis revealed higher Cryptosporidium infection prevalence in ungulates of the Cetartiodactyla than in those of the Perissodactyla, with cattle (29%) being the most commonly infected farm animal.

Conclusions

Overall, the investigated domestic ungulates are considered potential sources of Cryptosporidium contamination in the environment. Control measures should be developed to reduce the occurrence of Cryptosporidium infection in these animals. Furthermore, literature on wild populations of the named ungulate species revealed a widespread presence and potential reservoir function of wildlife.
Comparative study of excretory–secretory proteins released by Schistosoma mansoni-resistant, susceptible and naïve Biomphalaria glabrata
Authors: Fogarty Conor E. , Zhao Min , McManus Donald P. , Duke Mary G. , Cummins Scott F. , Wang Tianfang
Published: September 2019

Background

Schistosomiasis is a harmful neglected tropical disease caused by infection withSchistosomaspp., such asSchistosoma mansoni.Schistosomamust transition within a molluscan host to survive. Chemical analyses of schistosome-molluscan interactions indicate that host identification involves chemosensation, including naïve host preference. Proteomic technique advances enable sophisticated comparative analyses between infected and naïve snail host proteins. This study aimed to compare resistant, susceptible and naïveBiomphalaria glabratasnail-conditioned water (SCW) to identify potential attractants and deterrents.

Methods

Behavioural bioassays were performed onS. mansonimiracidia to compare the effects of susceptible, F1 resistant and naïveB. glabrataSCW. The F1 resistant and susceptibleB. glabrataSCW excretory–secretory proteins (ESPs) were fractionated using SDS-PAGE, identified with LC-MS/MS and compared to naïve snail ESPs. Protein-protein interaction (PPI) analyses based on published studies (including experiments, co-expression, text-mining and gene fusion) identifiedS. mansoniandB. glabrataprotein interaction. Data are availableviaProteomeXchange with identifier PXD015129.

Results

A total of 291, 410 and 597 ESPs were detected in the susceptible, F1 resistant and naïve SCW, respectively. Less overlap in ESPs was identified between susceptible and naïve snails than F1 resistant and naïve snails. F1 resistantB. glabrataESPs were predominately associated with anti-pathogen activity and detoxification, such as leukocyte elastase and peroxiredoxin. SusceptibleB. glabrataseveral proteins correlated with immunity and anti-inflammation, such as glutathione S-transferase and zinc metalloproteinase, andS. mansonisporocyst presence. PPI analyses found that uncharacterisedS. mansoniprotein Smp_142140.1 potentially interacts with numerousB. glabrataproteins.

Conclusions

This study identified ESPs released by F1 resistant, susceptible and naïveB. glabratato explainS. mansonimiracidia interplay. SusceptibleB. glabrataESPs shed light on potentialS. mansonimiracidia deterrents. Further targeted research on specific ESPs identified in this study could help inhibitB. glabrataandS. mansoniinteractions and stop human schistosomiasis.
Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids—clinical implication of primary prophylaxis using trimethoprim–sulfamethoxazole
Authors: Park Jun Won , Curtis Jeffrey R. , Kim Min Jung , Lee Hajeong , Song Yeong Wook , Lee Eun Bong
Published: September 2019

Objectives

To investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis.

Methods

This study included 28,292 treatment episodes with prolonged (≥ 4 weeks), non-high-dose steroids (low dose [< 15 mg/day, n = 27,227] and medium dose [≥ 15 to < 30 mg/day, n = 1065], based on prednisone) over a 14-year period. Risk factors for PCP and prophylactic effect of trimethoprim–sulfamethoxazole (TMP-SMX) were investigated if the 1-year incidence rate (IR) of PCP in each dose group was > 0.1/100 person-years. Cox regression with LASSO was used for analysis.

Results

One-year PCP IR in the low-dose group was 0.01 (95% CI 0.001–0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2–1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n = 173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1–8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR = 0.2 (0.001–2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3–71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17–226)) was lower than the number needed to harm by serious ADR (45 (15–∞)).

Conclusion

Incidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.
Sustained remission with methotrexate monotherapy after 22-week induction treatment with TNF-alpha inhibitor and methotrexate in early psoriatic arthritis: an open-label extension of a randomized placebo-controlled trial
Authors: de Jong Henriëtte M. Y. , van Mens Leonieke J. J. , Nurmohamed Michael T. , Kok Marc R. , van Kuijk Arno W. R. , Baeten Dominique L. P. , van de Sande Marleen G. H.
Published: September 2019

Background

If TNF inhibitors are initiated in the early stages of psoriatic arthritis, this could potentially modulate disease and therefore allow us to discontinue the TNF inhibitor after achieving remission.

Objective

To investigate whether remission induced by tumour necrosis factor alpha inhibitor (TNFi) and methotrexate in patients with early psoriatic arthritis is sustained after withdrawal of TNFi.

Methods

Open-label extension of a recently published double-blind, randomized placebo-controlled trial. Patients with psoriatic arthritis fulfilling the CASPAR criteria and with active disease at baseline (swollen and tender joint count ≥ 3) were randomized to either golimumab and methotrexate or matched placebo and methotrexate. Patients in Disease Activity Score (DAS) remission at week 22 continued in the open-label extension on methotrexate monotherapy. The primary end point was the percentage of patients in DAS-CRP remission (DAS < 1.6) at week 50.

Results

Eight patients from the original placebo group and 18 patients from the original TNFi group continued in the extension phase. At week 50, 6 out of 8 (75%) patients from the original MTX (methotrexate) group versus 10 out of 18 (56%) patients from the original MTX+TNFi group were in DAS-CRP remission (p = 0.347). Considering the total study population, 6 out of 24 (25%) of the original MTX group versus 10 out of 26 (38.5%) of the original MTX+TNFi group were in DAS remission at week 50 (p = 0.308).

Conclusions

Remission achieved by initial combination treatment with TNFi and methotrexate in early psoriatic arthritis is maintained on methotrexate monotherapy in approximately half of the patients.

Trial registration

Registered at Clinicaltrials.gov with number NCT01871649 on June 7, 2013.
A complex teamwork intervention in a surgical ward in Norway
Authors: Aaberg Oddveig Reiersdal , Hall-Lord Marie Louise , Husebø Sissel Iren Eikeland , Ballangrud Randi
Published: September 2019

Objectives

Interprofessional team training has a positive impact on team behavior and patient safety culture. The overall objective of the study was to explore the impact of an interprofessional teamwork intervention in a surgical ward on structure, process and outcome. In this paper, the implementation of the teamwork intervention is reported to expand the understanding of the future evaluation results of this study.

Results

The evidence-based Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) program was implemented in three phases according to the program’s implementation plan, which are built on Kotter’s organizational change model. In the first phase, a project group with the leaders and researchers was established and information about the project was given to all health care personnel in the ward. The second phase comprised 6 h interprofessional team training for all frontline health care personnel followed by 12 months implementation of TeamSTEPPS tools and strategies. In the third phase, the implementation of the tools and strategies continued, and refresher training was conducted.

Trial registration Trial registration number (TRN) is ISRCTN13997367. The study was registered retrospectively with registration date May 30, 2017
Determinants of stillbirth in Felege-Hiwot comprehensive specialized referral hospital, North-west, Ethiopia, 2019
Authors: Worede Daniel Tarekegn , Dagnew Gizachew Worku
Published: September 2019

Objective

The objective of this study was to identify determinants of stillbirth in Felege Hiwot comprehensive specialized referral hospital, North-west, Ethiopia: 2019. To conduct this study an institutional-based unmatched case–control study was used among 84 cases and 336 controls. Pretested, structured questioner with face to face interview was conducted and some data were also extracted from medical records using a checklist. The data were analyzed by using binary logistics regression. A p-value of < 0.05 was considered as significant at 95% confidence level and the strength of association was measured using odds ratio.

Results

Illiteracy (AOR 3.8, 95% CI 1.4–10.2), sexually transmitted infection (AOR 5.7, 95% CI 1.1–29.7), Premature rupture of membrane (AOR 4.0, 95% CI 1.4–11.3), congenital anomaly (AOR 10.4, 95% CI 2.0–11.2) and history of perinatal death (AOR 10.4, 95% CI 3.7–29.2) were the determinants of stillbirth that increase risk of fetal death. Whereas taking at least two doses of tetanus toxoid vaccine (AOR 0.5, 95% CI 0.2–0.9) and partograph use (AOR 0.2, 95% CI 0.1–0.4) were found to be protective factors for stillbirth. To overcome this problem; empowering female education, facilitating women in taking tetanus toxoid vaccine, sexually transmitted infection prevention, and encourage health professionals to use partograph during labour follow up highly strongly recommended.
Acute human bocavirus 1 infection in child with life-threatening bilateral bronchiolitis and right-sided pneumonia: a case report
Authors: Ziemele Inga , Xu Man , Vilmane Anda , Rasa-Dzelzkaleja Santa , Hedman Lea , Hedman Klaus , Söderlund-Venermo Maria , Nora-Krukle Zaiga , Murovska Modra , Gardovska Dace
Published: September 2019

Background

Human bocavirus 1 is a commonly detected human parvovirus. Many studies have shown human bocavirus 1 as a pathogen in association with acute respiratory tract infections in children. However, because human bocavirus 1 persists in the upper airways for extensive time periods after acute infection, the definition and diagnostics of acute human bocavirus 1 infection is challenging. Until now, detection of human bocavirus 1 exclusively, high viral load in respiratory samples, and viremia have been associated with a clinical picture of acute respiratory illness. There are no studies showing detection of human bocavirus 1 messenger ribonucleic acid in the peripheral blood mononuclear cells as a diagnostic marker for acute lower respiratory tract infection.

Case presentation

We report the case of a 17-month-old Latvian boy who presented in intensive care unit with acute bilateral bronchiolitis, with a history of rhinorrhea and cough for 6 days and fever for the last 2 days prior to admission, followed by severe respiratory distress and tracheal intubation. Human bocavirus 1 was the only respiratory virus detected by a qualitative multiplex polymerase chain reaction panel. For the diagnosis of acute human bocavirus 1 infection, both molecular and serological approaches were used. Human bocavirus 1 deoxyribonucleic acid (DNA) was detected simultaneously in nasopharyngeal aspirate, stool, and blood, as well as in the corresponding cell-free blood plasma by qualitative and quantitative polymerase chain reaction, revealing high DNA-copy numbers in nasopharyngeal aspirate and stool. Despite a low-load viremia, human bocavirus 1 messenger ribonucleic acid was found in the peripheral blood mononuclear cells. For detection of human bocavirus 1-specific antibodies, non-competitive immunoglobulin M and competitive immunoglobulin G enzyme immunoassays were used. The plasma was positive for both human bocavirus 1-specific immunoglobulin M and immunoglobulin G antibodies.

Conclusions

The presence of human bocavirus 1 genomic DNA in blood plasma and human bocavirus 1 messenger ribonucleic acid in peripheral blood mononuclear cells together with human bocavirus 1-specific immunoglobulin M are markers of acute human bocavirus 1 infection that may cause life-threatening acute bronchiolitis.
Response mechanism of hypocrellin colorants biosynthesis by Shiraia bambusicola to elicitor PB90
Authors: Du Wen , Sun Chunlong , Wang Baogui , Wang Yanmei , Dong Bin , Liu Junhua , Xia Jiangbao , Xie Wenjun , Wang Jun , Sun Jingkuan , Liu Xuehong , Wang Hongguo
Published: September 2019

The valuable medicine Shiraia bambusicola P. Henn. and its major active substance hypocrellin exert unique curative effects on skin diseases, diabetes, and cancers. The wild S. bambusicola is endangered due to its harsh breeding conditions and long growth cycle. It is one of the effective ways to utilize the resources sustainably to produce hypocrellin by fermentation of S. bambusicola. PB90 is a protein elicitor isolated from Phytophthora boehmeriae to induce the useful metabolites production in fungi. In this work, PB90 was selected to promote the synthesis hypocrellin by S. bambusicola. To evaluate the effect of PB90 on S. bambusicola, it was found that the induced cells showed decreased biomass, increased cell wall permeability, rapid induction of secondary metabolites, and significant increase of some enzyme activities, which confirmed a strong activation of phenylalanine/flavonoid pathways. Studies on signal molecules and gene expression level in S. bambusicola treated with PB90 have found that hydrogen peroxide (H2O2) and nitric oxide (NO) are necessary signal molecules involved in the synthesis of hypocrellin in elicited cells, and increased their signal levels through mutual reaction. We have showed for the first time, the response mechanism of hypocrellin biosynthesis from S. bambusicola to PB90, which may be not only establish a theoretical foundation for the application of PB90 to the mass production of S. bambusicola, but can also motivate further research on the application of PB90 to the conservation and sustainable utilization of other medical fungi.