bluuebunny/crossref_metadata_2025 huggingface dataset:
The biology of pulmonary exacerbations in bronchiectasis
Authors: Amati Francesco , Simonetta Edoardo , Gramegna Andrea , Tarsia Paolo , Contarini Martina , Blasi Francesco , Aliberti Stefano
Published: November 2019

Bronchiectasis is a heterogeneous chronic disease. Heterogeneity characterises bronchiectasis not only in the stable state but also during exacerbations, despite evidence on clinical and biological aspects of bronchiectasis, exacerbations still remain poorly understood.

Although the scientific community recognises that bacterial infection is a cornerstone in the development of bronchiectasis, there is a lack of data regarding other trigger factors for exacerbations. In addition, a huge amount of data suggest a primary role of neutrophils in the stable state and exacerbation of bronchiectasis, but the inflammatory reaction involves many other additional pathways. Cole's vicious cycle hypothesis illustrates how airway dysfunction, airway inflammation, infection and structural damage are linked. The introduction of the concept of a “vicious vortex” stresses the complexity of the relationships between the components of the cycle. In this model of disease, exacerbations work as a catalyst, accelerating the progression of disease. The roles of microbiology and inflammation need to be considered as closely linked and will need to be investigated in different ways to collect samples. Clinical and translational research is of paramount importance to achieve a better comprehension of the pathophysiology of bronchiectasis, microbiology and inflammation both in the stable state and during exacerbations.
Identification of key genes and regulators associated with carotenoid metabolism in apricot (Prunus armeniaca) fruit using weighted gene coexpression network analysis
Authors: Zhang Lina , Zhang Qiuyun , Li Wenhui , Zhang Shikui , Xi Wanpeng
Published: November 2019

Background

Carotenoids are a class of terpenoid pigments that contribute to the color and nutritional value of many fruits. Their biosynthetic pathways have been well established in a number of plant species; however, many details of the regulatory mechanism controlling carotenoid metabolism remain to be elucidated. Apricot is one of the most carotenoid-rich fruits, making it a valuable system for investigating carotenoid metabolism. The purpose of this study was to identify key genes and regulators associated with carotenoid metabolism in apricot fruit based on transcriptome sequencing.

Results

During fruit ripening in the apricot cultivar ‘Luntaixiaobaixing’ (LT), the total carotenoid content of the fruit decreased significantly, as did the levels of the carotenoids β-carotene, lutein and violaxanthin (p < 0.01). RNA sequencing (RNA-Seq) analysis of the fruit resulted in the identification of 44,754 unigenes and 6916 differentially expressed genes (DEGs) during ripening. Among these genes, 33,498 unigenes were annotated using public protein databases. Weighted gene coexpression network analysis (WGCNA) showed that two of the 13 identified modules (‘blue’ and ‘turquoise’) were highly correlated with carotenoid metabolism, and 33 structural genes from the carotenoid biosynthetic pathway were identified. Network visualization revealed 35 intramodular hub genes that putatively control carotenoid metabolism. The expression levels of these candidate genes were determined by quantitative real-time PCR analysis, which showed ripening-associated carotenoid accumulation. This analysis revealed that a range of genes (NCED1, CCD1/4, PIF3/4, HY5, ERF003/5/12, RAP2–12, AP2, AP2-like, BZR1, MADS14, NAC2/25, MYB1R1/44, GLK1/2 and WRKY6/31/69) potentially affect apricot carotenoid metabolism during ripening. Based on deciphering the molecular mechanism involved in ripening, a network model of carotenoid metabolism in apricot fruit was proposed.

Conclusions

Overall, our work provides new insights into the carotenoid metabolism of apricot and other species, which will facilitate future apricot functional studies and quality breeding through molecular design.
Infection and RNA-seq analysis of a zebrafish tlr2 mutant shows a broad function of this toll-like receptor in transcriptional and metabolic control and defense to Mycobacterium marinum infection
Authors: Hu Wanbin , Yang Shuxin , Shimada Yasuhito , Münch Magnus , Marín-Juez Rubén , Meijer Annemarie H. , Spaink Herman P.
Published: November 2019

Background

The function of Toll-like receptor 2 (TLR2) in host defense against pathogens, especially Mycobacterium tuberculosis (Mtb) is poorly understood. To investigate the role of TLR2 during mycobacterial infection, we analyzed the response of tlr2 zebrafish mutant larvae to infection with Mycobacterium marinum (Mm), a close relative to Mtb, as a model for tuberculosis. We measured infection phenotypes and transcriptome responses using RNA deep sequencing in mutant and control larvae.

Results

tlr2 mutant embryos at 2 dpf do not show differences in numbers of macrophages and neutrophils compared to control embryos. However, we found substantial changes in gene expression in these mutants, particularly in metabolic pathways, when compared with the heterozygote tlr2+/− control. At 4 days after Mm infection, the total bacterial burden and the presence of extracellular bacteria were higher in tlr2−/− larvae than in tlr2+/−, or tlr2+/+ larvae, whereas granuloma numbers were reduced, showing a function of Tlr2 in zebrafish host defense. RNAseq analysis of infected tlr2−/− versus tlr2+/− shows that the number of up-regulated and down-regulated genes in response to infection was greatly diminished in tlr2 mutants by at least 2 fold and 10 fold, respectively. Analysis of the transcriptome data and qPCR validation shows that Mm infection of tlr2 mutants leads to decreased mRNA levels of genes involved in inflammation and immune responses, including il1b, tnfb, cxcl11aa/ac, fosl1a, and cebpb. Furthermore, RNAseq analyses revealed that the expression of genes for Maf family transcription factors, vitamin D receptors, and Dicps proteins is altered in tlr2 mutants with or without infection. In addition, the data indicate a function of Tlr2 in the control of induction of cytokines and chemokines, such as the CXCR3-CXCL11 signaling axis.

Conclusion

The transcriptome and infection burden analyses show a function of Tlr2 as a protective factor against mycobacteria. Transcriptome analysis revealed tlr2-specific pathways involved in Mm infection, which are related to responses to Mtb infection in human macrophages. Considering its dominant function in control of transcriptional processes that govern defense responses and metabolism, the TLR2 protein can be expected to be also of importance for other infectious diseases and interactions with the microbiome.
Coordination of care for multimorbid patients from the perspective of general practitioners – a qualitative study
Authors: Stumm Judith , Thierbach Cornelia , Peter Lisa , Schnitzer Susanne , Dini Lorena , Heintze Christoph , Döpfmer Susanne
Published: November 2019

Background

In Germany, a decreasing number of general practitioners (GPs) face a growing number of patients with multimorbidity. Whilst care for patients with multimorbidity involves various healthcare providers, the coordination of this care is one of the many responsibilities of GPs. The aims of this study are to identify the barriers to the successful coordination of multimorbid patient care and these patients’ complex needs, and to explore the support needed by GPs in the care of multimorbid patients. Interviewees were asked for their opinion on concepts which involve the support by additional employees within the practice or, alternatively, external health care professionals, providing patient navigation.

Methods

Thirty-two semi-structured, qualitative interviews were conducted with 16 GPs and 16 medical practice assistants (MPAs) from 16 different practices in Berlin. A MPA is a qualified non-physician practice employee. He or she undergoes a three years vocational training which qualifies him or her to provide administrative and clinical support.

The interviews were digitally recorded, transcribed and analysed using the framework analysis methodology.

Results

The results of this paper predominantly focus on GPs’ perspectives of coordination within and external to general practice. Coordination in the context of care for multimorbid patients consists of a wide range of different tasks. Organisational and administrative obstacles under the regulatory framework of the German healthcare system, and insufficient communication with other healthcare providers constitute barriers described by the interviewed GPs and MPAs. In order to ensure optimal care for patients with multimorbidity, GPs may have to delegate responsibilities associated with coordinating tasks. GPs consider the deployment of an additional specifically qualified employee inside the general practice to take on coordinative and social and legal duties to be a viable option.

Conclusions

The cross-sectoral cooperation between all involved key players working within the healthcare system, as well as the coordination of the whole care process, is seemingly challenging for GPs within the complex care system of multimorbid patients. GPs are generally open to the assignment of a person to support them in coordination tasks, preferably situated within the practice team.
Estimating extra length of stay and risk factors of mortality attributable to healthcare-associated infection at a Chinese university hospital: a multi-state model
Authors: Zhou Qian , Fan Lili , Lai Xiaoquan , Tan Li , Zhang Xinping
Published: November 2019

Background

The current evidence of extra length of stay (LOS) attributable to healthcare-associated infection (HCAI) scarcely takes time-dependent bias into consideration. Plus, limited evidences were from developing countries. We aim to estimate the extra LOS and risk factors of mortality attributable to HCAI for inpatients.

Methods

Multi-state model (MSM) was adopted to estimate the extra LOS attributable to HCAI of each type and subgroup. COX regression model was used to examine the risk of mortality.

Results

A total of 51,691 inpatients were included and 1709 (3.31%) among them developed HCAI. Lower respiratory tract infection and Acinetobacter baumannii were the most prevalent HCAI and causative pathogen in surveyed institute. Generally, the expected extra LOS attributable to HCAI was 2.56 days (95% confidence interval: 2.54–2.61). Patients below 65 had extra LOS attributable to HCAI longer about 2 days than those above. The extra LOS attributable to HCAI of male patients was 1.33 days longer than female. Meanwhile, age above 65 years old and HCAI were the risk factors of mortality for inpatients.

Conclusions

HCAI contributes to an increase in extra LOS of inpatients in China. The effect of HCAI on extra LOS is different among subgroups, with the age below 65, male and medicine department more sensitive.
MRI-based radiomics of rectal cancer: preoperative assessment of the pathological features
Authors: Ma Xiaolu , Shen Fu , Jia Yan , Xia Yuwei , Li Qihua , Lu Jianping
Published: November 2019

Background

This study aimed to evaluate the significance of MRI-based radiomics model derived from high-resolution T2-weighted images (T2WIs) in predicting tumor pathological features of rectal cancer.

Methods

A total of 152 patients with rectal cancer who underwent surgery without any neoadjuvant therapy between March 2017 and September 2018 were included retrospectively. The patients were scanned using a 3-T magnetic resonance imaging, and high-resolution T2WIs were obtained. Lesions were delineated, and 1029 radiomics features were extracted. Least absolute shrinkage and selection operator was used to select features, and multilayer perceptron (MLP), logistic regression (LR), support vector machine (SVM), decision tree (DT), random forest (RF), and K-nearest neighbor (KNN) were trained using fivefold cross-validation to build a prediction model. The diagnostic performance of the prediction models was assessed using the receiver operating characteristic curves.

Results

A total of 1029 features were extracted, and 15, 11, and 11 features were selected to predict the degree of differentiation, T stage, and N stage, respectively. The best performance of the radiomics model for the degree of differentiation, T stage, and N stage was obtained by SVM [area under the curve (AUC), 0.862; 95% confidence interval (CI), 0.750–0.967; sensitivity, 83.3%; specificity, 85.0%], MLP (AUC, 0.809; 95% CI, 0.690–0.905; sensitivity, 76.2%; specificity, 74.1%), and RF (AUC, 0.746; 95% CI, 0.622-0.872; sensitivity, 79.3%; specificity, 72.2%).

Conclusion

This study demonstrated that the high-resolution T2WI–based radiomics model could serve as pretreatment biomarkers in predicting pathological features of rectal cancer.
Public-private partnerships and the politics of alcohol policy in England: the Coalition Government’s Public Health ‘Responsibility Deal’
Authors: Hawkins Benjamin , McCambridge Jim
Published: November 2019

Background

The 2010–2015 Conservative-led Coalition Government launched their flagship Public Health Responsibility Deal (PHRD) for England in 2011; a year before their alcohol strategy. This co-regulatory regime placed alcohol industry actors at the heart of policy-making, but was viewed with scepticism by public health actors. This article examines the ways in which the PHRD structured the alcohol policy environment throughout this period, which included the rejection of evidence-based policies such as minimum unit pricing.

Methods

This article draws on 26 semi-structured interviews with policy actors (parliamentarians, civil servants, civil society actors and academics) in 2018. Respondents were identified and recruited using purposive sampling. Interviews were recorded, transcribed and analysed using thematic coding.

Results

The PHRD shaped the context of alcohol policy development at Westminster throughout this period. It circumscribed the policy space by taking evidence-based measures not amenable to industry partnership off the agenda. While the PHRD created important opportunities for industry engagement with policy-makers, it undermined public health actors’ access to government, particularly following their withdrawal from the process. Moreover, the PHRD demonstrates the enduring appeal of partnership as a policy idea for governments, despite a lack of evidence of their effectiveness.

Conclusions

This study of the PHRD demonstrates the ways in which industry actors are able to influence policy through long-term relationship building and partnership working on policy decision-making. Whilst such partnership approaches may appear to have the potential to mitigate some of alcohol harms, they create fundamental conflicts of interest, and may undermine the very causes they seek to further.
Increased lactic acid content associated with extracellular matrix depletion in a porcine disc degeneration induced by superficial annular lesion
Authors: Shi Jinhui , Zhou Xichao , Wang Zhen , Kurra Swamy , Niu Junjie , Yang Huilin
Published: November 2019

Background

Degenerative intervertebral disc (IVD) disease can cause lower back pain. However, the change of lactic acid content during disc degeneration process still unclear. The objective of this study was to investigate whether the change of the content of lactic acid is associated with depletion of degenerative intervertebral disc extracellular matrix.

Methods

A total of 18 miniature pigs were equally divided into annular lesion surgery (AL) and sham group. The lateral superficial annulus fibrosus (AF) of T12-L4 discs in AL group were penetrated by 3.5 mm trepan with the depth of 3 mm, the same IVD were only exposed without any injury in the sham group. At 4, 8 and 12 weeks after surgery, the degree of intervertebral disc degeneration was evaluated by magnetic resonance, histological and biochemical analysis.

Results

No obvious degeneration was found in sham group. However, disc degeneration was found and gradually worsened in AL group after surgery. Histological analysis showed that the AF was rupture and disorder, the number of cells in nucleus pulposus (NP) was decreased in AL group. Compared with the sham group, the extent of type II collagen (Col-II) and aggrecan in NP tissue was dramatically decreased in AL group, consistent with the results of Col -II immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Besides, the gene expression of matrix metallopeptidase 3 and 13 also continuous increased in AL group. The amount of lactic acid and nerve growth factor in NP tissue was gradually increased after operation in AL group.

Conclusions

The content of lactic acid gradually increased after annular lesion, associated with the damage of AF structural and the decrease of Col -II and aggrecan in NP tissue, which leading to the disc degeneration. Depletion of extracellular matrix is consistent with lactic acid accumulation inside of IVD.
Diagnostic criteria of periprosthetic joint infection: a prospective study protocol to validate the feasibility of the 2018 new definition for Chinese patients
Authors: Guan Haitao , Xu Chi , Fu Jun , Ni Ming , Li Xiang , Chai Wei , Hao Libo , Zhou Yonggang , Chen Jiying
Published: November 2019

Background

Periprosthetic joint infection (PJI) is a challenging complication following total joint arthroplasty (TJA), and the diagnostic criteria remains controversial. The 2018 new definition proposed in May 2018 consists of new diagnostic criteria for PJI. We conducted a retrospective study and demonstrated that the new definition could improve the diagnostic efficiency in Chinese patients. However, missing data led to bias in the previous retrospective study. Therefore, this prospective study is designed to further validate the feasibility of 2018 new definition (and its modified version) for Chinese patients.

Methods/design

This is a single-centre, prospective diagnostic study with 1 year of follow-up. The patients enrolled in the trial will be divided into a PJI group and an Aseptic group based on the eligibility criteria. We will recruit at least 70 patients for each group from October 2019 to October 2020. Blood samples, synovial fluid samples and intraoperative variables of all the included patients will be collected to assess various indicators. We will integrate the results of the various tests and examine the diagnostic efficiency (sensitivity and specificity) of five diagnostic criteria.

Discussion

We design the prospective study in the hope of reducing the bias caused by missing data. Therefore, the prospective study will further support the conclusion of our preceding retrospective study. The results of this study will be submitted to a peer-reviewed journal for publication.

Conclusion

Through this prospective study, we will validate the feasibility of the 2018 new PJI definition (and its modified version) for Chinese patients and determine the optimal method of PJI diagnosis.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1900025395. Registered on 25 August 2019.
Towards improved health service quality in Tanzania: contribution of a supportive supervision approach to increased quality of primary healthcare
Authors: Renggli Sabine , Mayumana Iddy , Mboya Dominick , Charles Christopher , Mshana Christopher , Kessy Flora , Glass Tracy R. , Lengeler Christian , Schulze Alexander , Aerts Ann , Pfeiffer Constanze
Published: November 2019

Background

Universal Health Coverage only leads to the desired health outcomes if quality of health services is ensured. In Tanzania, quality has been a major concern for many years, including the problem of ineffective and inadequate routine supportive supervision of healthcare providers by council health management teams. To address this, we developed and assessed an approach to improve quality of primary healthcare through enhanced routine supportive supervision.

Methods

Mixed methods were used, combining trends of quantitative quality of care measurements with qualitative data mainly collected through in-depth interviews. The former allowed for identification of drivers of quality improvements and the latter investigated the perceived contribution of the new supportive supervision approach to these improvements.

Results

The results showed that the new approach managed to address quality issues that could be solved either solely by the healthcare provider, or in collaboration with the council. The new approach was able to improve and maintain crucial primary healthcare quality standards across different health facility level and owner categories in various contexts.

Conclusion

Together with other findings reported in companion papers, we could show that the new supportive supervision approach not only served to assess quality of primary healthcare, but also to improve and maintain crucial primary healthcare quality standards. The new approach therefore presents a powerful tool to support, guide and drive quality improvement measures within council. It can thus be considered a suitable option to make routine supportive supervision more effective and adequate.
Nasal epithelial cells to assess in vitro immune responses to respiratory virus infection in pregnant women with asthma
Authors: Vanders Rebecca L. , Hsu Alan , Gibson Peter G. , Murphy Vanessa E. , Wark Peter A. B.
Published: November 2019

Respiratory virus-induced asthma exacerbations occur frequently during pregnancy and are associated with adverse outcomes for mother and child. Primary nasal epithelial cells (pNECs) provide a useful method to study immune responses in pregnancy. pNECs were obtained by nasal brushings from pregnant and non-pregnant women with and without asthma. pNECS were infected in vitro with major group Rhinovirus 43 (RV43) and seasonal influenza (H3N2). Following infection, pNECs showed measurable quantities of interferon (IFN)-λ, IL-1β, IL-8, IP-10 and MIP1-α. pNECs provide a safe and effective method for studying respiratory epithelial cell responses during pregnancy.
Value of muscle magnetic resonance imaging in the differential diagnosis of muscular dystrophies related to the dystrophin-glycoprotein complex
Authors: Xie Zhiying , Xie Zhihao , Yu Meng , Zheng Yiming , Sun Chengyue , Liu Yilin , Ling Chen , Zhu Ying , Zhang Wei , Xiao Jiangxi , Wang Zhaoxia , Yuan Yun
Published: November 2019

Background

Dystrophin-glycoprotein complex (DGC)-related muscular dystrophies may present similar clinical and pathological features as well as undetectable mutations thus being sometimes difficult to distinguish. We investigated the value of muscle magnetic resonance imaging (MRI) in the differential diagnosis of DGC-related muscular dystrophies and reported the largest series of Chinese patients with sarcoglycanopathies studied by muscle MRI.

Results

Fifty-five patients with DGC-related muscular dystrophies, including 22 with confirmed sarcoglycanopathies, 11 with limb-girdle muscular dystrophy 2I (LGMD2I, FKRP-associated dystroglycanopathy), and 22 with dystrophinopathies underwent extensive clinical evaluation, muscle biopsies, genetic analysis, and muscle MRI examinations. Hierarchical clustering of patients according to the clinical characteristics showed that patients did not cluster according to the genotypes. No statistically significant differences were observed between sarcoglycanopathies and LGMD2I in terms of thigh muscle involvement. The concentric fatty infiltration pattern was observed not only in different sarcoglycanopathies (14/22) but also in LGMD2I (9/11). The trefoil with single fruit sign was observed in most patients with dystrophinopathies (21/22), and a few patients with sarcoglycanopathies (4/22) or LGMD2I (2/11). Hierarchical clustering showed that most patients with sarcoglycanopathies or LGMD2I can be distinguished from dystrophinopathies based on the concentric fatty infiltration pattern and trefoil with single fruit sign at the thigh level on muscle MRI.

Conclusions

Muscle MRI at the thigh level potentially allows distinction of sarcoglycanopathies or FKRP-associated dystroglycanopathy from dystrophinopathies.
Programmatic implications for promotion of handwashing behavior in an internally displaced persons camp in North Kivu, Democratic Republic of Congo
Authors: Blum Lauren S. , Yemweni Anicet , Trinies Victoria , Kambere Mimi , Tolani Foyeke , Allen Jelena V. , Handzel Thomas , Cookson Susan , Ram Pavani K.
Published: November 2019

Background

Diarrhea and acute respiratory infections (ARI) account for 30% of deaths among children displaced due to humanitarian emergencies. A wealth of evidence demonstrates that handwashing with soap prevents both diarrhea and ARI. While socially- and emotionally-driven factors are proven motivators to handwashing in non-emergency situations, little is known about determinants of handwashing behavior in emergency settings.

Methods

We conducted a qualitative investigation from June to August 2015 in a camp for internally displaced persons with a population of 6360 in the war-torn eastern region of the Democratic Republic of Congo. We held key informant interviews with 9 non-governmental organizations and camp officials, in-depth interviews and rating exercises with 18 mothers of children < 5 years, and discussions with 4 groups of camp residents and hygiene promoters to identify motivators and barriers to handwashing.

Results

At the time of the study, hygiene promotion activities lacked adequate resources, cultural acceptability, innovation, and adaptation for sustained behavioral change. Lack of ongoing provision of hygiene materials was a major barrier to handwashing behavior. When hygiene materials were available, camp residents reported that the primary motivator to handwashing was to prevent illness, particularly diarrheal disease, with many mentioning an increased need to wash hands during diarrhea outbreaks. Emotionally- and socially-related motivators such as “maintaining a good image” and social pressure to follow recommended camp hygiene practices were also reported to motivate handwashing with soap. Residents who engaged in day labor outside the camp had limited exposure to hygiene messages and handwashing facilities. Interviewees indicated that the harsh living conditions forced residents to prioritize obtaining basic survival needs over good hygiene.

Conclusions

Hygiene promotion in camp settings must involve preparedness of adequate resources and supplies and ongoing provision of hygiene materials so that vulnerable populations affected by emergencies can apply good hygiene behaviors for the duration of the camp’s existence. Compared to non-emergency contexts, illness-based messages may be more effective in emergency settings where disease poses a current and ongoing threat. However, failure to use emotive and social drivers that motivate handwashing may present missed opportunities to improve handwashing in camps.
Point-of-care ultrasound in primary care: a systematic review of generalist performed point-of-care ultrasound in unselected populations
Authors: Sorensen Bjarte , Hunskaar Steinar
Published: November 2019

Background

Both the interest and actual extent of use of point-of-care ultrasound, PoCUS, among general practitioners or family physicians are increasing and training is also increasingly implemented in residency programs. However, the amount of research within the field is still rather limited compared to what is seen within other specialties in which it has become more established, such as in the specialty of emergency medicine. An assumption is made that what is relevant for emergency medicine physicians and their populations is also relevant to the general practitioner, as both groups are generalists working in unselected populations. This systematic review aims to examine the extent of use and to identify clinical studies on the use of PoCUS by either general practitioners or emergency physicians on indications that are relevant for the former, both in their daily practice and in out-of-hours services.

Methods

Systematic searches were done in PubMed/MEDLINE using terms related to general practice, emergency medicine, and ultrasound.

Results

On the extent of use, we identified 19 articles, as well as 26 meta-analyses and 168 primary studies on the clinical use of PoCUS. We found variable, but generally low, use among general practitioners, while it seems to be thoroughly established in emergency medicine in North America, and increasingly also in the rest of the world. In terms of clinical studies, most were on diagnostic accuracy, and most organ systems were studied; the heart, lungs/thorax, vessels, abdominal and pelvic organs, obstetric ultrasound, the eye, soft tissue, and the musculoskeletal system. The studies found in general either high sensitivity or high specificity for the particular test studied, and in some cases high total accuracy and superiority to other established diagnostic imaging modalities. PoCUS also showed faster time to diagnosis and change in management in some studies.

Conclusion

Our review shows that generalists can, given a certain level of pre-test probability, safely use PoCUS in a wide range of clinical settings to aid diagnosis and better the care of their patients.
Occupational hazards in medium and large scale industrial sectors in Sri Lanka: experience of a developing country
Authors: Arnold S. M. , Wickrematilake M. S. K. , Fernando R. M. S. D. , Sampath H. M. R. C. , Karunapema R. P. P. , Mahesh P. K. B. , Munasinghe P. M. , Denawaka C. J.
Published: November 2019

Objective

Occupational hazards is an area where many countries have begun to pay more emphasis as it affects the health of many particularly in developing countries. However, documented literature is scarce in this regard although occupational hazards are common in workplaces. The study was carried out with the objective of describing the physical hazards and control measures adopted in the formal medium and large-scale industrial sector in Sri Lanka.

Results

Of the 69 units of the 25 factories, physical hazards detected in the workplaces were; excessive noise (78.3%), poor light (58%), increased temperature (65.2%), and poor ventilation (68.1%). Over 50% of large machinery and 33% of medium-scale machinery were not adequately guarded. Nearly 41% of the machinery were difficult to operate, of them 36.2% had controls in positions which were hard to reach. Of safety measures adopted, only 34.8% had proper demarcation of areas with 28.9% displaying safety signs. Housekeeping was poor in 59.4% and less than 40% had safe storage of raw materials and end products.
Tissue immune profiles supporting response to mesenchymal stromal cell therapy in acute graft-versus-host disease—a gut feeling
Authors: Gavin Caroline , Boberg Erik , Von Bahr Lena , Bottai Matteo , Andrén Anton Törnqvist , Wernerson Annika , Davies Lindsay C. , Sugars Rachael V. , Le Blanc Katarina
Published: November 2019

Acute graft-versus-host disease (aGvHD), post-allogeneic hematopoietic stem cell transplantation, is associated with high mortality rates in patients not responding to standard line care with steroids. Adoptive mesenchymal stromal cell (MSC) therapy has been established in some countries as a second-line treatment.

Limitations in our understanding as to MSC mode of action and what segregates patient responders from non-responders to MSC therapy remain. The principal aim of this study was to evaluate the immune cell profile in gut biopsies of patients diagnosed with aGvHD and establish differences in baseline cellular composition between responders and non-responders to subsequent MSC therapy.

Our findings indicate that a pro-inflammatory immune profile within the gut at the point of MSC treatment may impede their therapeutic potential. These findings support the need for further validation in a larger cohort of patients and the development of improved biomarkers in predicting responsiveness to MSC therapy.
Putative metabolic pathway for the bioproduction of bikaverin and intermediates thereof in the wild Fusarium oxysporum LCP531 strain
Authors: Lebeau Juliana , Petit Thomas , Dufossé Laurent , Caro Yanis
Published: November 2019

Fungal naphthoquinones, like red bikaverin, are of interest due to their growing applications in designing pharmaceutical products. Though considerable work has been done on the elucidation of bikaverin biosynthesis pathway in Fusarium fujikuroi, very few reports are available regarding its bioproduction in F. oxysporum. We are hereby proposing a putative metabolic pathway for bikaverin bioproduction in a wild F. oxysporum strain by cross-linking the pigment profiles we obtained under two different fermentation conditions with literature. Naphthoquinone pigments were extracted with a pressurized liquid extraction method, and characterized by HPLC–DAD and UHPLC-HRMS. The results led to the conclusions that the F. oxysporum LCP531 strain was able to produce bikaverin and its various intermediates, e.g., pre-bikaverin, oxo-pre-bikaverin, dinor-bikaverin, me-oxo-pre-bikaverin, and nor-bikaverin, in submerged cultures in various proportions. To our knowledge, this is the first report of the isolation of these five bikaverin intermediates from F. oxysporum cultures, providing us with steady clues for confirming a bikaverin metabolic pathway as well as some of its regulatory patterns in the F. oxysporum LCP531 strain, based on the previously reported model in F. fujikuroi. Interestingly, norbikaverin accumulated along with bikaverin in mycelial cells when the strain grew on simple carbon and nitrogen sources and additional cofactors. Along bikaverin production, we were able to describe the excretion of the toxin beauvericin as main extrolite exclusively in liquid medium containing complex nitrogen and carbon sources, as well as the isolation of ergosterol derivate in mycelial extracts, which have potential for pharmaceutical uses. Therefore, culture conditions were also concluded to trigger some specific biosynthetic route favoring various metabolites of interest. Such observation is of great significance for selective production of pigments and/or prevention of occurrence of others (aka mycotoxins).
Interventions for oropharyngeal dysphagia in acute and critical care: a protocol for a systematic review and meta-analysis
Authors: Duncan Sallyanne , Gaughey Jennifer Mc , Fallis Richard , McAuley Daniel F. , Walshe Margaret , Blackwood Bronagh
Published: November 2019

Background

Oropharyngeal dysphagia or swallowing difficulties are common in acute care and critical care, affecting 47% of hospitalised frail elderly, 50% of acute stroke patients and approximately 62% of critically ill patients who have been intubated and mechanically ventilated for prolonged periods. Complications of dysphagia include aspiration leading to chest infection and pneumonia, malnutrition, increased length of hospital stay and re-admission to hospital. To date, most dysphagia interventions in acute care have been tested with acute stroke populations. While intervention studies in critical care have been emerging since 2015, they are limited and so there is much to learn about the type, the delivery and the intensity of treatments in this setting to inform future clinical trials. The aim of this systematic review is to summarise the evidence regarding the relationship between dysphagia interventions and clinically important patient outcomes in acute and critical care settings.

Methods

We will search MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL and clinical trial registries from inception to the present. We will include studies conducted with adults in acute care settings such as acute hospital wards or units or intensive care units and critical care settings. Studies will be restricted to randomised controlled trials and quasi-randomised controlled trials comparing a new dysphagia intervention with usual care or another intervention. The main outcomes that will be collected include length of time taken to return to oral intake, change in incidence of aspiration and pneumonia, nutritional status, length of hospital stay and quality of life. Key intervention components such as delivery, intensity, acceptability, fidelity and adverse events associated with such interventions will be collected to inform future clinical trials. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. A meta-analysis will be conducted as appropriate.

Discussion

No systematic review has attempted to summarise the evidence for oropharyngeal dysphagia interventions in acute and critical care. Results of the proposed systematic review will inform practice and the design of future clinical trials.

Systematic review registration

PROSPERO CRD 42018116849 (http://www.crd.york.ac.uk/PROSPERO/)
A new accelerated conjugate gradient method for large-scale unconstrained optimization
Authors: Chen Yuting , Cao Mingyuan , Yang Yueting
Published: November 2019

In this paper, we present a new conjugate gradient method using an acceleration scheme for solving large-scale unconstrained optimization. The generated search direction satisfies both the sufficient descent condition and the Dai–Liao conjugacy condition independent of line search. Moreover, the value of the parameter contains more useful information without adding more computational cost and storage requirements, which can improve the numerical performance. Under proper assumptions, the global convergence result of the proposed method with a Wolfe line search is established. Numerical experiments show that the given method is competitive for unconstrained optimization problems, with a maximum dimension of 100,000.
Phenotypic and genotypic characterization of carbapenem-resistant Acinetobacter baumannii isolates from Egypt
Authors: Abouelfetouh Alaa , Torky Aisha S. , Aboulmagd Elsayed
Published: November 2019

Background

Antibiotic use is largely under-regulated in Egypt leading to the emergence of resistant isolates. Carbapenems are last resort agents to treatAcinetobacter baumanniiinfections resistant to other classes of antibiotics. However, carbapenem-resistant isolates are emerging at an alarming rate. This study aimed at phenotypically and molecularly characterizing seventy four carbapenem-unsusceptibleA. baumanniiisolates from Egypt to detect the different enzymes responsible for carbapenem resistance.

Methods

Carbapenemase production was assessed by a number of phenotypic methods: modified Hodge test (MHT), carbapenem inactivation method (CIM), combined disc test (CDT), CarbAcineto NP test and boronic acid disc test. Polymerase chain reaction (PCR) was used to screen the isolates for the presence of some genes responsible for resistance to carbapenems, as well as some insertion sequences.

Results

PCR amplification of class D carbapenemases revealed the prevalence ofblaOXA-51andblaOXA-23in 100% of the isolates and ofblaOXA-58in only one isolate (1.4%).blaVIMandblaNDM-1belonging to class B metallo-β-lactamases were present in 100 and 12.1% of the isolates, respectively. The prevalence of ISAba1, ISAba2and ISAba3was 100, 2.7 and 4.1%, respectively. None of the tested isolates carriedblaOXA-40,blaIMP,blaSIM,blaSPM,blaGIMor the class AblaKPC. Taking PCR as the gold standard method for the detection of different carbapenemases, the sensitivities of the MHT, CIM, CDT, CarbAcineto NP test and boronic acid disc/imipenem or meropenem test for this particular collection of isolates were 78.4, 68.9, 79.7, 95.9, and 56.8% or 70.3%, respectively.

Conclusions

The widespread detection of carbapenem-resistantA. baumannii(CR-AB) has become a real threat to the efficacy of treatment regimens. Among the studied cohort of CR-AB clinical isolates,blaOXA-51,blaOXA-23andblaVIMwere the most prevalent, followed byblaNDM-1andblaOXA-58. The genotypic detection of carbapenemases among CR-AB clinical isolates using PCR was most conclusive, followed closely by the phenotypic testing using CarbAcineto NP test.
The impact of a sterile processing program in Northwest Tanzania: a mixed-methods study
Authors: Fast Olive , Uzoka Faith-Michael , Cuncannon Alexander , Fast Christina , Dosani Aliyah , Nyanza Elias Charles , Fast Dan , Maduka Theresia
Published: November 2019

Background

Inadequate training of health care workers responsible for the sterilization of surgical instruments in low- and middle-income countries compromises the safety of workers and patients alike.

Methods

A mixed methods research study was initiated in the Lake Zone areas of Northwestern Tanzania in the summer of 2018. The goal was to identify the impact of education and training on sterile processing practices at ten hospitals. Quantitative data analyzed included hospital assessments of sterile processing practices prior to and 4 months after training, as well as participant test scores collected at the beginning of training, after 5 days of classes, and 4 months after mentorship was completed. Thematic analysis of interviews with participants 4 months post-training was completed to identify associated impact of training.

Results

Improvement in test scores were found to be directly related to sterile processing training. The greatest sterile processing practice changes identified through hospital assessments involved how instruments were cleaned, both at point of use and during the cleaning process, resulting in rusted and discoloured instruments appearing as new again. Themes identified in participant interviews included: changes in practice, challenges in implementing practice changes, resource constraints, personal and professional growth, and increased motivation, confidence and responsibility.

Conclusions

Providing education and follow up support for workers in sterile processing resulted in increased knowledge of best practices, application of knowledge in practice settings, and awareness of issues that need to be overcome to decrease risks for patients and health care workers alike. Further research is needed to identify the impact of mentorship on hospital sterile processing practices in order to provide clear direction for future spending on training courses.
Developing global image feature analysis models to predict cancer risk and prognosis
Authors: Zheng Bin , Qiu Yuchen , Aghaei Faranak , Mirniaharikandehei Seyedehnafiseh , Heidari Morteza , Danala Gopichandh
Published: November 2019

In order to develop precision or personalized medicine, identifying new quantitative imaging markers and building machine learning models to predict cancer risk and prognosis has been attracting broad research interest recently. Most of these research approaches use the similar concepts of the conventional computer-aided detection schemes of medical images, which include steps in detecting and segmenting suspicious regions or tumors, followed by training machine learning models based on the fusion of multiple image features computed from the segmented regions or tumors. However, due to the heterogeneity and boundary fuzziness of the suspicious regions or tumors, segmenting subtle regions is often difficult and unreliable. Additionally, ignoring global and/or background parenchymal tissue characteristics may also be a limitation of the conventional approaches. In our recent studies, we investigated the feasibility of developing new computer-aided schemes implemented with the machine learning models that are trained by global image features to predict cancer risk and prognosis. We trained and tested several models using images obtained from full-field digital mammography, magnetic resonance imaging, and computed tomography of breast, lung, and ovarian cancers. Study results showed that many of these new models yielded higher performance than other approaches used in current clinical practice. Furthermore, the computed global image features also contain complementary information from the features computed from the segmented regions or tumors in predicting cancer prognosis. Therefore, the global image features can be used alone to develop new case-based prediction models or can be added to current tumor-based models to increase their discriminatory power.
Hyperandrogenism in polycystic ovarian syndrome and role of CYP gene variants: a review
Authors: Ashraf Sairish , Nabi Mudasar , Rasool Shayaq ul Abeer , Rashid Fouzia , Amin Shajrul
Published: November 2019

Background

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. The pathophysiology of PCOS is not clear; however, disturbance in hypothalamic-pituitary-ovarian axis and abnormal steroidogenesis along with genetic and environmental factors act as main contributors to this disorder.

Main text

Hyperandrogenism, the hallmark feature of PCOS, is clinically manifested as hirsutism, acne, and alopecia. Excessive androgen production by ovaries as well as from adrenals contributes to hyperandrogenism. Abnormalities in the neuroendocrine system like increased pulse frequency of gonadotropin-releasing hormone, stimulating the pituitary for excessive production of luteinizing hormone than that of follicle-stimulating hormone is seen in PCOS women. Excess LH stimulates ovarian androgen production, whereas a relative deficit in FSH impairs follicular development. The imbalance in LH: FSH causes proliferation of ovarian theca cells leading to increased steroidogenesis, and ultimately leading to hyperandrogenism in PCOS women. Various genetic factors have been shown to be associated with abnormal steroidogenesis. CYP genes involved in steroidogenesis play an important role in androgen production and are considered as key players in hyperandrogenism in PCOS.

Conclusion

Polymorphisms in CYP genes can aggravate the hyperandrogenic phenotype in women with PCOS by either upregulating or downregulating their expression, thus increasing androgens further. However, this hypothesis needs to be validated by further studies.
Aberrant methylation of yes-associated protein (YAP1) as a potential biomarker in breast cancer
Authors: Ramadan Ragaa Abdelkader , Elkarmouty Ahmed , Elnaggar Mostafa
Published: November 2019

Background

Breast cancer (BC) represents the most prevalent malignancy among women, and it is characterized by high mortality especially in late stages. BC tumorigenesis was linked to epigenetic alterations namely methylation. Yes-associated protein (YAP1) is the leading downstream effector of the Hippo pathway. It may enhance or inhibit oncogenesis based on the tissue involved.

Aim

This case-control study aimed to analyze the methylation degree of promoter region of YAP1 gene in BC patients by applying methylation-specific polymerase chain reaction (MSP) analysis.

Methods

Genomic deoxyribonucleic acid (DNA) was isolated from 50 paired tumor and adjacent noncancerous breast tissue samples and subjected to bisulfite conversion. Methylation condition of YAP1 gene was studied by MSP and evaluated as a possible biomarker for diagnosing BC and its differentiation from corresponding normal tissues. We also correlated the aberrant methylation with clinicopathological criteria.

Results

Increased methylation of the YAP1 gene promoter region in BC tumor tissue was detected in 68% of the studied BC tissue samples. There was a significant change in the frequency of YAP1 methylated genotype between breast tumor tissues compared to that in adjacent non-cancerous tissue (p < 0.001). YAP1 can discriminate early from late-stage BC with a sensitivity of 96.88% and specificity of 83.33%.

Conclusions

Gene analysis of YAP1 using conventional MSP in tissue specimens can be considered a possible biomarker to distinguish BC from normal breast tissue as well as between early- and late-stage BC.