bluuebunny/crossref_metadata_2025 huggingface dataset:
The ultrastructural damage caused by Eugenia zeyheri and Syzygium legatii acetone leaf extracts on pathogenic Escherichia coli
Authors: Famuyide Ibukun M. , Fasina Folorunso O. , Eloff Jacobus N. , McGaw Lyndy J.
Published: September 2020

Background

Antibiotics are commonly added to livestock feeds in sub-therapeutic doses as growth promoters and for prophylaxis against pathogenic microbes, especially those implicated in diarrhoea. While this practice has improved livestock production, it is a major cause of antimicrobial resistance in microbes affecting livestock and humans. This has led to the banning of prophylactic antibiotic use in animals in many countries. To compensate for this, alternatives have been sought from natural sources such as plants. While many studies have reported the antimicrobial activity of medicinal plants with potential for use as phytogenic/botanical feed additives, little information exists on their mode of action. This study is based on our earlier work and describes ultrastructural damage induced by acetone crude leaf extracts of Syzygium legatii and Eugenia zeyheri (Myrtaceae) active against diarrhoeagenic E. coli of swine origin using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescent microscopy (FM). Gas chromatography/mass spectrometry (GC-MS) was used to investigate the chemical composition of plant extracts.

Results

The extracts damaged the internal and external anatomy of the cytoplasmic membrane and inner structure at a concentration of 0.04 mg/mL. Extracts also led to an increased influx of propidium iodide into treated bacterial cells suggesting compromised cellular integrity and cellular damage. Non-polar compounds such as α-amyrin, friedelan-3-one, lupeol, and β-sitosterol were abundant in the extracts.

Conclusions

The extracts of S. legatii and E. zeyheri caused ultrastructural damage to E. coli cells characterized by altered external and internal morphology. These observations may assist in elucidating the mode of action of the extracts.
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers
Authors: Nascimento Emmani B. M. , Hangelbroek Roland W. J. , Hooiveld Guido J. E. J. , Hoeks Joris , Van Marken Lichtenbelt Wouter D. , Hesselink Matthijs H. C. , Schrauwen Patrick , Kersten Sander
Published: September 2020

Background

Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training.

Methods

To investigate if cold acclimation and exercise training overlap in the molecular adaptive response in skeletal muscle, we performed transcriptomics analysis on vastus lateralis muscle collected from human subjects before and after 10 days of cold acclimation, as well as before and after a 12-week exercise training intervention.

Results

Cold acclimation altered the expression of 756 genes (422 up, 334 down, P < 0.01), while exercise training altered the expression of 665 genes (444 up, 221 down, P < 0.01). Principal Component Analysis, Venn diagram, similarity analysis and Rank–rank Hypergeometric Overlap all indicated significant overlap between cold acclimation and exercise training in upregulated genes, but not in downregulated genes. Overlapping gene regulation was especially evident for genes and pathways associated with extracellular matrix remodeling. Interestingly, the genes most highly induced by cold acclimation were involved in contraction and in signal transduction between nerve and muscle cells, while no significant changes were observed in genes and pathways related to insulin signaling or glucose metabolism.

Conclusions

Overall, our results indicate that cold acclimation and exercise training have overlapping effects on gene expression in human skeletal muscle, but strikingly these overlapping genes are designated to pathways related to tissue remodeling rather than metabolic pathways.
Inducible intracellular membranes: molecular aspects and emerging applications
Authors: Royes Jorge , Biou Valérie , Dautin Nathalie , Tribet Christophe , Miroux Bruno
Published: September 2020

Membrane remodeling and phospholipid biosynthesis are normally tightly regulated to maintain the shape and function of cells. Indeed, different physiological mechanisms ensure a precise coordination between de novo phospholipid biosynthesis and modulation of membrane morphology. Interestingly, the overproduction of certain membrane proteins hijack these regulation networks, leading to the formation of impressive intracellular membrane structures in both prokaryotic and eukaryotic cells. The proteins triggering an abnormal accumulation of membrane structures inside the cells (or membrane proliferation) share two major common features: (1) they promote the formation of highly curved membrane domains and (2) they lead to an enrichment in anionic, cone-shaped phospholipids (cardiolipin or phosphatidic acid) in the newly formed membranes. Taking into account the available examples of membrane proliferation upon protein overproduction, together with the latest biochemical, biophysical and structural data, we explore the relationship between protein synthesis and membrane biogenesis. We propose a mechanism for the formation of these non-physiological intracellular membranes that shares similarities with natural inner membrane structures found in α-proteobacteria, mitochondria and some viruses-infected cells, pointing towards a conserved feature through evolution. We hope that the information discussed in this review will give a better grasp of the biophysical mechanisms behind physiological and induced intracellular membrane proliferation, and inspire new applications, either for academia (high-yield membrane protein production and nanovesicle production) or industry (biofuel production and vaccine preparation).
Improving public hospital efficiency and fiscal space implications: the case of Mauritius
Authors: Nundoochan Ajoy
Published: September 2020

Background

General Government Health Expenditure (GGHE) in Mauritius accounted for only 10% of General Government Expenditure for the fiscal year 2018. This is less than the pledge taken under the Abuja 2001 Declaration to allocate at least 15% of national budget to the health sector. The latest National Health Accounts also urged for an expansion in the fiscal space for health. As public hospitals in Mauritius absorb 70% of GGHE, maximising returns of hospitals is essential to achieve Universal Health Coverage. More so, as Mauritius is bracing for its worst recession in 40 years in the aftermath of the COVID-19 pandemic public health financing will be heavily impacted. A thorough assessment of hospital efficiency and its implications on effective public health financing and fiscal space creation is, therefore, vital to inform ongoing health reform agenda.

Objectives

This paper aims to examine the trend in hospital technical efficiency over the period 2001–2017, to measure the elasticity of hospital output to changes in inputs variables and to assess the impact of improved hospital technical efficiency in terms of fiscal space creation.

Methods

Annual health statistics released by the Ministry of Health and Wellness and national budget of the Ministry of Finance, Economic Planning and Development were the principal sources of data. Applying Stochastic Frontier Analysis, technical efficiency of public regional hospitals was estimated under Cobb–Douglas, Translog and Multi-output distance functions, using STATA 11. Hospital beds, doctors, nurses and non-medical staff were used as input variables. Output variable combined inpatients and outpatients seen at Accident Emergency, Sorted and Unsorted departments. Efficiency scores were used to determine potential efficiency savings and fiscal space creation.

Findings

Mean technical efficiency scores, using the Cobb Douglas, Translog and Multi-output functions, were estimated at 0.83, 0.84 and 0.89, respectively. Nurses and beds are the most important factors in hospital production, as a 1% increase in the number of beds and nurses, result in an increase in hospital outputs by 0.73 and 0.51%, respectively. If hospitals are to increase their inputs by 1%, their outputs will increase by 1.16%. Hospital output process has an increasing return to scale. With technical efficiencies improving to scores of 0.95 and 1.0 in 2021–2022, potential savings and fiscal space creation at hospital level, would amount to MUR 633 million (US$ 16.2 million) and MUR 1161 million (US$ 29.6 million), respectively.

Conclusion

Fiscal space creation through full technical efficiency, is estimated to represent 8.9 and 9.2% of GGHE in fiscal year 2021–2022 and 2022–2023, respectively. This will allow without any restrictions the funding of the national response for HIV, vaccine preventable diseases as well as building a resilient health system to mitigate impact of emerging infectious diseases as experienced with COVID-19.
Correction to: YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma
Authors: Hou Jiajie , Zhang He , Liu Jun , Zhao Zhenjun , Wang Jianye , Lu Zhike , Hu Bian , Zhou Jiankui , Zhao Zhicong , Feng Mingxuan , Zhang Haiyan , Shen Bin , Huang Xingxu , Sun Beicheng , Smyth Mark J. , He Chuan , Xia Qiang
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Factors affecting health-related quality of life in patients with skin disease: cross-sectional results from 8,789 patients with 16 skin diseases
Authors: He Zehui , Marrone Gaetano , Ou Aihua , Liu Hongxia , Ma Lin , Huang Ying , Li Yongmei , Sun Liyun , Bai Yanping , Liu Wali , Zha Xushan , Lu Chuanjian
Published: September 2020

Background

Many previous studies have reported factors that contribute to health-related quality of life (HRQoL) for a single skin disease. However, little is known about generalized factors associated with HRQoL across skin diseases. The objective of this study was to investigate overall HRQoL, and to identify factors related to severely impaired HRQoL among patients with 16 different skin diseases.

Methods

A cross-sectional study of 9845 patients with skin disease was conducted in 9 hospitals in China. HRQoL was assessed with the Chinese version of the Skindex-29 which measures dermatology-specific health along three domains (symptoms, emotions and functioning). With the published Skindex-29 cut-off scores for severely impaired HRQoL, logistic regression models assessed the relationship between severely impaired HRQoL and demographic/clinical characteristics, with adjustments for different skin diseases. To guarantee the models’ convergence, 16 skin diseases with frequencies of at least 100 were included, and the sample size was 8789.

Results

Emotions was the most impaired aspect of HRQoL. Co-existing chronic diseases, 3 years or longer duration, and more severity were identified as associated factors for severely impaired HRQoL for each Skindex-29 domain, and for the aggregate. Being female, under 45 years old, and consuming alcohol were associated with a severely impaired emotion domain; Lack of exercise and smoking were associated with severely impaired symptoms and function domains, respectively.

Conclusions

Skin diseases can affect many facets of HRQoL, but the emotional impairment deserves more attention. In addition to skin disease severity, this study shows that other chronic diseases and long duration are correlated with severely impaired HRQoL for patients with 16 clinical common skin diseases. This suggests the need for increased awareness in treating skin disease as a chronic disease. It also suggests that disease management decisions should consider HRQoL improvement, especially emotional conditions, when making management decisions.
Measuring positive mental health and flourishing in Denmark: validation of the mental health continuum-short form (MHC-SF) and cross-cultural comparison across three countries
Authors: Santini Ziggi Ivan , Torres-Sahli Manuel , Hinrichsen Carsten , Meilstrup Charlotte , Madsen Katrine R. , Rayce Signe Boe , Baker Melissa M. , Ten Have Margreet , Schotanus-Dijkstra Marijke , Koushede Vibeke
Published: September 2020

Background

The Mental Health Continuum–Short Form (MHC-SF) is a measure of positive mental health and flourishing, which is widely used in several countries but has not yet been validated in Denmark. This study aimed to examine its qualitative and quantitative properties in a Danish population sample and compare scores with Canada and the Netherlands.

Methods

Three thousand five hundred eight participants aged 16–95 filled out an electronic survey. Both the unidimensional and multidimensional aspects of the Danish MHC-SF were studied through bifactor modelling. Cognitive interviews examined face validity and usability.

Results

The general score of the Danish MHC-SF was reliable for computing unit-weighted composite scores, as well as using a bifactor model to compute general factor scores or measurement models in an SEM context. Nonetheless, subscale scores were unreliable, explaining very low variance beyond that explained by the general factor. The participants of the qualitative interviews observed problems with wording and content of the items, especially from the social subscale. The general score correlated with other scales as expected. We found substantial variation in flourishing prevalence rates between the three cultural settings.

Conclusions

The Danish MHC-SF produced reliable general scores of well-being. Most of the issues observed regarding the subscale scores have been shown in previous research in other contexts. The further analysis of indices of the bifactor model and the inclusion of qualitative interviews allowed for a better understanding of the possible sources of problems with the questionnaire’s subscales. The use of subscales, the substantive understanding of the general score, as well as the operationalization of the state of flourishing, require further study.
Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report)
Authors: Dell’Anno Irene , Barone Elisa , Mutti Luciano , Rassl Doris M. , Marciniak Stefan J. , Silvestri Roberto , Landi Stefano , Gemignani Federica
Published: September 2020

Background

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the pleura, mainly related to asbestos exposure. As in other solid tumors, malignant cells exhibit high glucose uptake and glycolytic rates with increased lactic acid efflux into the interstitial space. Lactate transport into and out of cells, crucial to maintaining intracellular pH homeostasis and glycolysis, is carried out by monocarboxylate transporters (MCTs) and the chaperone basigin (CD147). We set out to examine the clinical significance of basigin, MCT1 and MCT4 in the context of MPM and to evaluate their expression in relation to the evolution of the disease.

Methods

We used immunohistochemistry to measure the expression of basigin, MCT1 and MCT4 in a cohort of 135 individuals with MPM compared to a series of 15 non-MPM pleura specimens. Moreover, by Kaplan–Meier and Cox analyses we evaluated whether an expression over the average of these markers could be associated with the patients’ overall survival (OS).

Results

We detected positive staining of basigin, MCT1, and MCT4 in most MPM specimens. In particular, MCT4 was always positive in malignant tissues but undetectable in the 4 normal pleural specimens incorporated within the tissue microarray. This was confirmed in the additional series of 15 normal pleural samples. Moreover, MCT4 expression was significantly associated with reduced OS.

Conclusion

In this study, the tissue expression of basigin did not prove to be exploitable as a diagnostic or prognostic marker for MPM patients. The expression of MCT1 was not informative either, being tightly correlated with that of basigin. However, the expression of MCT4 showed promise as a diagnostic/therapeutic and prognostic biomarker.
A hypoxia-related signature for clinically predicting diagnosis, prognosis and immune microenvironment of hepatocellular carcinoma patients
Authors: Zhang Baohui , Tang Bufu , Gao Jianyao , Li Jiatong , Kong Lingming , Qin Ling
Published: September 2020

Background

Hypoxia plays an indispensable role in the development of hepatocellular carcinoma (HCC). However, there are few studies on the application of hypoxia molecules in the prognosis predicting of HCC. We aim to identify the hypoxia-related genes in HCC and construct reliable models for diagnosis, prognosis and recurrence of HCC patients as well as exploring the potential mechanism.

Methods

Differentially expressed genes (DEGs) analysis was performed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and four clusters were determined by a consistent clustering analysis. Three DEGs closely related to overall survival (OS) were identified using Cox regression and LASSO analysis. Then the hypoxia-related signature was developed and validated in TCGA and International Cancer Genome Consortium (ICGC) database. The Gene Set Enrichment Analysis (GSEA) was performed to explore signaling pathways regulated by the signature. CIBERSORT was used for estimating the fractions of immune cell types.

Results

A total of 397 hypoxia-related DEGs in HCC were detected and three genes (PDSS1, CDCA8 and SLC7A11) among them were selected to construct a prognosis, recurrence and diagnosis model. Then patients were divided into high- and low-risk groups. Our hypoxia-related signature was significantly associated with worse prognosis and higher recurrence rate. The diagnostic model also accurately distinguished HCC from normal samples and nodules. Furthermore, the hypoxia-related signature could positively regulate immune response. Meanwhile, the high-risk group had higher fractions of macrophages, B memory cells and follicle-helper T cells, and exhibited higher expression of immunocheckpoints such as PD1and PDL1.

Conclusions

Altogether, our study showed that hypoxia-related signature is a potential biomarker for diagnosis, prognosis and recurrence of HCC, and it provided an immunological perspective for developing personalized therapies.
Genetic and environmental determinants of human TCR repertoire diversity
Authors: Krishna Chirag , Chowell Diego , Gönen Mithat , Elhanati Yuval , Chan Timothy A.
Published: September 2020

T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on the diversity of the TCR repertoire remains unclear. Here, we analyzed a cohort of 666 individuals with TCR repertoire sequencing. We show that TCR repertoire diversity is positively associated with polymorphism at the human leukocyte antigen class I (HLA-I) loci, and diminishes with age and cytomegalovirus (CMV) infection. Moreover, our analysis revealed that HLA-I polymorphism and age independently shape the repertoire in healthy individuals. Our data elucidate key determinants of human TCR repertoire diversity, and suggest a mechanism underlying the evolutionary fitness advantage of HLA-I heterozygosity.
Locoregional recurrence patterns in women with breast cancer who have not undergone post-mastectomy radiotherapy
Authors: Zhao Xuran , Tang Yu , Wang Shulian , Yang Yong , Fang Hui , Wang Jianyang , Jing Hao , Zhang Jianghu , Sun Guangyi , Chen Siye , Jin Jing , Song Yongwen , Liu Yueping , Chen Bo , Qi Shunan , Li Ning , Tang Yuan , Lu Ningning , Ren Hua , Li Yexiong
Published: September 2020

Background

To analyze the patterns of locoregional recurrence in breast cancer patients after mastectomy.

Methods

The retrospective study included 7073 women with breast cancer without post-mastectomy radiotherapy: 4604 (65.1%) had pT1–2 N0 disease (low risk); 2042 (28.9%), pT1–2 N1 (intermediate risk); and 427 (6.0%), pT3–4 and/or pN2–3, or pT1–2 N1 after neoadjuvant chemotherapy (high risk). The distribution of cumulative locoregional recurrence was analyzed. The local recurrence and regional recurrence rates were estimated by the Kaplan-Meier method, and differences were compared with the log-rank test. Multivariate analysis was performed using Cox logistic regression analysis.

Results

In the median follow-up of 63.0 months, 469 patients had locoregional recurrence: chest wall recurrence in 238 (50.7%) cases, supraclavicular/infraclavicular nodes in 236 (50.3%) cases, axilla in 92 (19.6%), and internal mammary nodes in 50 (10.7%) cases. The 5-year local recurrence and regional recurrence rates were 2.5 and 4.4%, respectively. Subgroup analysis of the three risk groups and five molecular subtypes (luminal A, luminal B-Her2 negative, luminal B-Her2 positive, Her2-enriched, and triple negative) also showed that the chest wall and supraclavicular/infraclavicular nodes were the most common recurrence sites. Age, tumor location, T stage, N stage, and hormone receptor status were independent prognostic factors for both local recurrence and regional recurrence (p < 0.05).

Conclusions

The chest wall and supraclavicular/infraclavicular nodes are common sites of locoregional recurrence in breast cancer, irrespective of disease stage or molecular subtype, and the prognostic factors for local recurrence and regional recurrence are similar. Therefore, chest wall and supraclavicular/infraclavicular nodes irradiation should always be considered in post-mastectomy radiotherapy.
Finite element modeling of proximal femur with quantifiable weight-bearing area in standing position
Authors: Yang Peng , Lin Tian-Ye , Xu Jing-Li , Zeng Hui-Yu , Chen Da , Xiong Bing-Lang , Pang Feng-Xiang , Chen Zhen-Qiu , He Wei , Wei Qiu-Shi , Zhang Qing-Wen
Published: September 2020

The positional distribution and size of the weight-bearing area of the femoral head in the standing position as well as the direct active surface of joint force can directly affect the result of finite element (FE) stress analysis. However, the division of this area was vague, imprecise, and un-individualized in most studies related to separate FE models of the femur. The purpose of this study was to quantify the positional distribution and size of the weight-bearing area of the femoral head in standing position by a set of simple methods, to realize individualized reconstruction of the proximal femur FE model.

Five adult volunteers were recruited for an X-ray and CT examination in the same simulated bipedal standing position with a specialized patented device. We extracted these image data, calculated the 2D weight-bearing area on the X-ray image, reconstructed the 3D model of the proximal femur based on CT data, and registered them to realize the 2D weight-bearing area to 3D transformation as the quantified weight-bearing surface. One of the 3D models of the proximal femur was randomly selected for finite element analysis (FEA), and we defined three different loading surfaces and compared their FEA results.

A total of 10 weight-bearing surfaces in 5 volunteers were constructed, and they were mainly distributed on the dome and anterolateral of the femoral head with a crescent shape, in the range of 1218.63–1,871.06 mm2. The results of FEA showed that stress magnitude and distribution in proximal femur FE models among three different loading conditions had significant differences, and the loading case with the quantized weight-bearing area was more in accordance with the physical phenomenon of the hip.

This study confirmed an effective FE modeling method of the proximal femur, which can quantify the weight-bearing area to define a more reasonable load surface setting without increasing the actual modeling difficulty.
HIV Nef enhances the expression of oncogenic c-MYC and activation-induced cytidine deaminase in Burkitt lymphoma cells, promoting genomic instability
Authors: Mdletshe Nontlantla , Nel Andrew , Shires Karen , Mowla Shaheen
Published: September 2020

Background

Non-Hodgkin lymphoma is of high prevalence among HIV-infected people. In particular, the incidence of HIV-associated Burkitt lymphoma (BL) remains high despite the advent of Highly Active Anti-Retroviral Therapy. Recent evidence shows that serum-soluble HIV proteins can enhance oncogenesis, particularly in lymphoid tissues. This study sought to define the role of HIV protein Negative regulatory factor (Nef) in BL development by assessing its effect on key lymphoma driver genes.

Methods

A recombinant Nef protein was used to assess changes in expressions of activation-induced cytidine deaminase (AICDA/AID) and c-MYC in B lymphocytes exposed extracellularly to the protein. Additionally, changes in the promoter activities of these genes were measured using a Nef-expressing cellular model and reporter assays. Confocal microscopy was used to observe c-MYC and AID expression and localization, and genomic integrity via the recruitment of phosphorylated γ-H2AX, in Nef-exposed cells.

Results

mRNA transcription ofc-MYCandAICDAwere significantly enhanced in lymphoma cells, up to 2-fold forc-MYCand up to 4-fold forAICDA, when exposed to varying concentrations of Nef (0–1000 ng/ml) and for different periods of time (3, 6 and 12 h). The protein expressions of AID and c-MYC followed a similar pattern and these effects were specific to BL but not lymphoblastoid cells. While the promoter activity ofc-MYCwas enhanced in the presence of Nef in a dose-dependent manner, the same was not observed forAICDA. Both AID and c-MYC accumulated within the cytoplasmic and nuclear spaces of Nef-exposed lymphoma cells, with a concomitant increase in DNA double strand breaks within the genome.

Conclusions

Exposure to HIV Nef leads to significant increases in AID and c-MYC, leading to genomic instability, potentially enhancing the oncogenic potential of Burkitt lymphoma. Our findings align with that of others to show that HIV proteins can directly contribute to the development and pathogenesis of HIV-associated lymphoma and accounts for the elevated incidence of BL observed in the HIV-infected population.
Alexithymia 3.0: reimagining alexithymia from a medical perspective
Authors: Lane Richard D.
Published: September 2020

Background

Although alexithymia research has greatly expanded in recent decades, our ability to treat it clinically remains limited. This article provides a new perspective on why that may be true and offers a fresh approach to clinical intervention.

The recent distinction between the agnosia and anomia subtypes of alexithymia, coupled with the introduction of the three-process model of emotional awareness (consisting of affective response generation, affective response representation and cognitive control), suggests that alexithymia is a phenotype that includes a spectrum of deficits that vary in their underlying neurobiology. This advance creates the opportunity to improve our ability to treat alexithymia. In the history of medicine major advances in the ability to provide effective treatments became possible once the relevant underlying morbid anatomy and physiology were discovered and the different causes of a common clinical phenotype were identified. The author suggests that we may now be entering a new era of this type in alexithymia research and clinical care. According to this perspective, Era 1.0 consisted of the pioneering clinical observations of abnormalities in emotional functioning culminating in the consensus definition of alexithymia in Heidelberg in 1976. Era 2.0 from 1976 to the present has consisted of empirical studies in which sound psychometric measures based on this clinical phenotype have been used in combination with clinical assessments and objective measures such as emotion recognition ability, peripheral physiology and neuroimaging. We may now be entering Era 3.0 in which a new model of an alexithymia spectrum grounded in brain-body interactions can transcend the constraints of a phenotype standard and provide a guide for personalized clinical care targeting the specific deficits present in a given individual. This new approach is meant to supplement rather than replace existing research and clinical practices.

Conclusion

This new era constitutes a medical perspective in three ways: 1) a focus on underlying neurobiology and associated clinical manifestations rather than an overarching phenotype; 2) a focus on the mechanisms of brain-body interactions associated with alexithymia that lead to adverse outcomes in systemic medical disorders; 3) clinical treatments directed at the specific deficits present in any given case.
Evaluation of an intervention aimed at supporting new parents: the Baby Newsletter project
Authors: Panza Costantino , Volta Alessandro , Broccoli Serena , Bonvicini Laura , Kendall Sally , Marchesi Maddalena , Giorgi Rossi Paolo
Published: September 2020

Background

Anticipatory guidance for parents is commonly used to improve parenting skills. The objective of this pre/post-intervention controlled study was to evaluate the effectiveness of a periodic newsletter with advice on childcare and development in improving parenting self-efficacy.

Methods

This was a non-randomized pre/post-intervention controlled study.

All the parents of children born between September 2014 and December 2015 resident in the S. Ilario d’Enza municipality (Italy) received eight Baby Newsletters. Parents resident in other municipalities of the same Health District were the control. Parents with linguistic barriers or with preterm or hospitalized children were excluded.

Improvement in parenting self-efficacy was measured through the TOPSE (Tool to Measure Parenting Self-Efficacy) questionnaire during the first week (t0) after delivery and at 5 (t1) and 12 months (t2) of life at two vaccination appointments. A score ranging from 0 to 60 was computed for each of the eight domains investigated by the TOPSE.

Variations of each TOPSE score between delivery and 12 months in the two groups were compared, adjusting for parity, education, age of parents, and child’s sex, and stratifying by parity and education.

Results /findings

One hundred thirty-six families accepted to participate in the study. Scores at 12 months were higher than 1 week after delivery in both groups for all TOPSE domains. The improvement was slightly stronger in the Newsletter group for almost all the skills exceptlearning and knowledge[difference in the mean of variation: -0.48 (95% CI: − 3.17; 2.21)]; the difference was significant only forplay and enjoyment[2.18 (95% CI: 0.12; 4.25)]. The increase in scores in almost all domains was more pronounced for parents with high education level at first child.

Conclusions

The intervention was effective in improving parents’ ability to play. However, it risks worsening existing differences between parents with high and with low education levels.

Trial registration

Clinical trial registration:NCT03268408.
Health sequelae of human cryptosporidiosis in industrialised countries: a systematic review
Authors: Carter Bethan L. , Chalmers Rachel M. , Davies Angharad P.
Published: September 2020

Background

Cryptosporidium is a protozoan parasite which is a common cause of gastroenteritis worldwide. In developing countries, it is one of the most important causes of moderate to severe diarrhoea in young children; in industrialised countries it is a cause of outbreaks of gastroenteritis associated with drinking water, swimming pools and other environmental sources and a particular concern in certain immunocompromised patient groups, where it can cause severe disease. However, over recent years, longer-term sequelae of infection have been recognised and a number of studies have been published on this topic. The purpose of this systematic review was to examine the literature in order to better understand the medium- to long-term impact of cryptosporidiosis.

Methods

This was a systematic review of studies in PubMed, ProQuest and Web of Science databases, with no limitations on publication year or language. Studies from any country were included in qualitative synthesis, but only those in industrialised countries were included in quantitative analysis.

Results

Fifteen studies were identified for qualitative analysis which included 3670 Cryptosporidium cases; eight studies conducted in Europe between 2004–2019 were suitable for quantitative analysis, including five case-control studies. The most common reported long-term sequelae were diarrhoea (25%), abdominal pain (25%), nausea (24%), fatigue (24%) and headache (21%). Overall, long-term sequelae were more prevalent following infection with Cryptosporidium hominis, with only weight loss and blood in stool being more prevalent following infection with Cryptosporidium parvum. Analysis of the case-control studies found that individuals were 6 times more likely to report chronic diarrhoea and weight loss up to 28 months after a Cryptosporidium infection than were controls. Long-term abdominal pain, loss of appetite, fatigue, vomiting, joint pain, headache and eye pain were also between 2–3 times more likely following a Cryptosporidium infection.

Conclusions

This is the first systematic review of the long-term sequelae of cryptosporidiosis. A better understanding of long-term outcomes of cryptosporidiosis is valuable to inform the expectations of clinicians and their patients, and public health policy-makers regarding the control and prevention of this infection.

Systematic review registration PROSPERO Registration number CRD42019141311
Spatial heterogeneity and temporal dynamics of mosquito population density and community structure in Hainan Island, China
Authors: Li Yiji , Zhou Guofa , Zhong Saifeng , Wang Xiaoming , Zhong Daibin , Hemming-Schroeder Elizabeth , Yi Guohui , Fu Fengyang , Fu Faxing , Cui Liwang , Cui Guzhen , Yan Guiyun
Published: September 2020

Background

Mosquitoes are vectors of many tropical diseases. Understanding the ecology of local mosquito vectors, such as species composition, distributions, population dynamics, and species diversity is important for designing the optimal strategy to control the mosquito-borne diseases.

Methods

Entomological surveillance of adult mosquitoes was conducted in five sites representing different ecological settings across Hainan Island from January to December of 2018 using BG Sentinel (BGS) traps and Centers for Disease Prevention and Control (CDC) light traps. In each site, we selected three areas representing urban, suburban and rural settings. Eighteen trap-days were sampled in each setting at each site, and CDC light traps and BGS traps were setup simultaneously. Mosquito species composition, distribution, population dynamics, and species diversity were analyzed. Mosquito densities were compared between different study sites and between different settings.

Results

Nine species of mosquitoes belonging to four genera were identified. Culex quinquefasciatus (80.8%), Armigeres subalbatus (13.0%) and Anopheles sinensis (3.1%) were the top three species collected by CDC light traps; Cx. quinquefasciatus (91.9%), Ae. albopictus (5.1%), and Ar. subalbatus (2.8%) were the top three species collected by BGS traps. Predominant species varied among study sites. The population dynamics of Ae. albopictus, An. sinensis and Cx. quinquefasciatus showed clear seasonal variation regardless of study sites with a varied peak season for different species. Mosquito abundance of all species showed significant differences among different study sites and among urban, suburban and rural areas. Danzhou had the highest mosquito biodiversity, with an α, β, and Gini-Simpson biodiversity index of 8, 1.13 and 0.42, respectively. BGS traps captured Aedes mosquito at a higher efficiency than CDC light traps, whereas CDC light traps captured significantly more Anopheles and Armigeres mosquitoes than BGS traps.

Conclusions

Mosquitoes were abundant on Hainan Island with clear seasonality and spatial heterogeneity. Population density, species composition, distribution, and species diversity were strongly affected by the natural environment. Different tools are required for the surveillance of different mosquito species.
DNA methylation suppresses chitin degradation and promotes the wing development by inhibiting Bmara-mediated chitinase expression in the silkworm, Bombyx mori
Authors: Xu Guanfeng , Yi Yangqin , Lyu Hao , Gong Chengcheng , Feng Qili , Song Qisheng , Peng Xuezhen , Liu Lin , Zheng Sichun
Published: September 2020

Background

DNA methylation, as an essential epigenetic modification found in mammals and plants, has been implicated to play an important role in insect reproduction. However, the functional role and the regulatory mechanism of DNA methylation during insect organ or tissue development are far from being clear.

Results

Here, we found that DNA methylation inhibitor (5-aza-dC) treatment in newly molted pupae decreased the chitin content of pupal wing discs and adult wings and resulted in wing deformity of Bombyx mori. Transcriptome analysis revealed that the up-regulation of chitinase 10 (BmCHT10) gene might be related to the decrease of chitin content induced by 5-aza-dC treatment. Further, the luciferase activity assays demonstrated that DNA methylation suppressed the promoter activity of BmCHT10 by down-regulating the transcription factor, homeobox protein araucan (Bmara). Electrophoretic mobility shift assay, DNA pull-down and chromatin immunoprecipitation demonstrated that Bmara directly bound to the BmCHT10 promoter. Therefore, DNA methylation is involved in keeping the structural integrity of the silkworm wings from unwanted chitin degradation, as a consequence, it promotes the wing development of B. mori.

Conclusions

This study reveals that DNA methylation plays an important role in the wing development of B. mori. Our results support that the indirect transcriptional repression of a chitin degradation-related gene BmCHT10 by DNA methylation is necessary to keep the proper wing development in B. mori.
Epidemiology of gout in Hong Kong: a population-based study from 2006 to 2016
Authors: Tsoi Man Fung , Chung Man Ho , Cheung Bernard Man Yung , Lau Chak Sing , Cheung Tommy Tsang
Published: September 2020

Objective

To determine the incidence and prevalence of gout in the general population and the utilisation of urate-lowering therapy (ULT) among patients with gout in Hong Kong.

Methods

A total of 2,741,862 subjects who attended any outpatient clinics or accident and emergency department (with or without hospitalisation) in 2005 and did not die before 2006 were identified from the Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority in Hong Kong. All subjects were followed until the end of 2016 or death.

Demographics, diagnosis of gout, serum urate levels, and ULT prescriptions were retrieved from CDARS. Gout was defined by the diagnosis codes in CDARS. The serum urate levels achieved after prescribing ULT were the means of all serum urate levels measured 6 months after prescriptions. Results were analysed by R version 3.3.3 with package ‘prevalence’ version 0.4.0.

Results

The crude incidence of gout increased from 113.05/100,000 person-years (PY) in 2006 to 211.62/100,000 PY in 2016. The crude prevalence of gout increased from 1.56% in 2006 to 2.92% in 2016. Only 25.55% of patients with gout were prescribed ULT in 2016. 35.8% of patients treated with ULT were able to achieve the target serum urate level of < 6 mg/dL.

Conclusions

Population ageing as well as other risk factors contributed to an increase in the incidence and prevalence of gout in Hong Kong. In 2016, the crude prevalence of gout in Hong Kong was comparable to that in many western countries. However, only one in four patients with gout in Hong Kong was prescribed ULT.
The role of Mycobacterium tuberculosis complex species on apoptosis and necroptosis state of macrophages derived from active pulmonary tuberculosis patients
Authors: Yanti Budi , Mulyadi Mulyadi , Amin Muhammad , Harapan Harapan , Mertaniasih Ni Made , Soetjipto Soetjipto
Published: September 2020

Objective

The role of Mycobacterium tuberculosis complex (MTBC) species in tuberculosis (TB) infection in human is still questioned. The aim of this study was to determine whether M. tuberculosis and M. bovis is associated with apoptosis and necroptosis by measuring the expression of specific signaling pathways components (Fas-associated protein with death domain (FADD) and receptor interacting protein 3 (RIP3)), and the level of apoptosis.

Results

We recruited 30 patients with pulmonary TB; 24 patients were infected with M. tuberculosis Beijing strain and six patients with M. bovis BCG strain. M. tuberculosis-infected patients were more likely to have severe lung damage compared to those infected with M. bovis (odds ratio [OR] 7.60; 95% confidence interval [CI] 1.07–54.09). M. tuberculosis infection was associated with lower expression of FADD and lower apoptosis level of macrophages compared to M. bovis. No significant different of RIP3 between MTBC species groups. In conclusion, M. tuberculosis Beijing strain was associated with severe pulmonary damage, inhibited FADD expression and reduced apoptosis level of macrophages derived from pulmonary TB patients. This suggests that the M. tuberculosis Beijing strain is potentially to be used as determinant of disease progressivity and tissue damage in TB cases.
Pyrosequencing scrutiny of bacterial and fungal communities in two Sudanese sorghum-based fermented foods
Authors: Eltayeb Mohamed Mutasim , Eltigani Sara Ahmed , Taniguchi Takeshi
Published: September 2020

Purpose

Several fermented foods are produced from sorghum flour in Africa, especially in the dryland regions where it is the principal crop. It is important to explore the microbial communities in these foods to improve their quality and organoleptic properties. In this study, the bacterial and fungal communities of two popular sorghum-based fermented foods in Sudan (kisra and hulumur) were analyzed, for the first time, using a culture-independent method of next-generation sequencing.

Methods

Fermented doughs for kisra and hulumur production were prepared according to the traditional approach, and then the bacterial and fungal communities were investigated using high-throughput sequencing.

Results

Firmicutes and Proteobacteria phyla were the predominant bacteria in both fermented doughs. At the genus level, the bacterial community was dominated by lactic acid bacteria, primarily Lactobacillus and Pediococcus, which represented 95.7% and 72% of the bacterial population in kisra and hulumur, respectively. Next, acetic acid bacteria (Gluconobacter and Acetobacter) were subdominant in hulumur. The fungal community was more heterogeneous among the fermented doughs. Zygomycota (85.5%) comprised the major phylum in kisra fermented dough, whereas Ascomycota (99.5%) was predominant in hulumur. The major fungal genera, Rhizopus, Alternaria, Penicillium, Gibberella, Lasiodiplodia, and Aspergillus, were extremely varied between the fermented doughs.

Conclusion

Exploration of kisra and hulumur microbial community structure will expand the knowledge about their microbiota to manipulate the microbial community and improve their quality and organoleptic properties using different microbial recipes.
DeepGraphMolGen, a multi-objective, computational strategy for generating molecules with desirable properties: a graph convolution and reinforcement learning approach
Authors: Khemchandani Yash , O’Hagan Stephen , Samanta Soumitra , Swainston Neil , Roberts Timothy J. , Bollegala Danushka , Kell Douglas B.
Published: September 2020

We address the problem of generating novel molecules with desired interaction properties as a multi-objective optimization problem. Interaction binding models are learned from binding data using graph convolution networks (GCNs). Since the experimentally obtained property scores are recognised as having potentially gross errors, we adopted a robust loss for the model. Combinations of these terms, including drug likeness and synthetic accessibility, are then optimized using reinforcement learning based on a graph convolution policy approach. Some of the molecules generated, while legitimate chemically, can have excellent drug-likeness scores but appear unusual. We provide an example based on the binding potency of small molecules to dopamine transporters. We extend our method successfully to use a multi-objective reward function, in this case for generating novel molecules that bind with dopamine transporters but not with those for norepinephrine. Our method should be generally applicable to the generation in silico of molecules with desirable properties.
Nuclear imaging methods for the prediction of postoperative morbidity and mortality in patients undergoing localized, liver-directed treatments: a systematic review
Authors: Espersen Caroline , Borgwardt Lise , Larsen Peter Nørgaard , Andersen Trine Borup , Stenholt Louise , Petersen Lars Jelstrup
Published: September 2020

Background

Several nuclear imaging methods may predict postoperative liver function and outcome, but none has achieved recommendations in clinical guidelines. The purpose of this systematic review was to summarize the existing knowledge on this topic.

Methods

MEDLINE and Web of Science were searched for studies investigating nuclear medicine imaging methods for the prediction of postoperative liver function in patients undergoing localized, liver-directed treatments. The postoperative endpoints were clinical outcome (morbidity and mortality) as well as measures of postoperative liver function, e.g., liver function assessed by biochemical tests or nuclear imaging.

Results

A total of 1352 references were identified, of which 82 fulfilled the eligibility criteria and were included in the review. Most studies (n = 63) were retrospective studies. The vast majority of studies assessed [99mTc]Tc-galactosyl serum albumin (GSA) (n = 57) and [99mTc]Tc-mebrofenin (n = 19). Liver resection was entirely or partly major (involved at least three segments) in 78 reports. There were notable variations in the research methodology, e.g., image acquisition, imaging variables, and endpoints. Thirty-seven studies reported on postoperative mortality, of which most reported descriptive data at the patient level. Of the four reports that performed multivariate analyses, two showed significant predictive results of isotope-based preoperative tests. Fifty-two papers presented data on postoperative liver failure. Multivariate predictive analyses were performed in eighteen trials, of which fifteen showed the significant value of nuclear medicine tests.

Conclusion

There is sparse evidence supporting the significant value of nuclear medicine imaging methods in predicting postoperative mortality. In contrast, a notable number of trials showed a significant prediction of liver failure in multivariate analyses. The research methodology was heterogeneous and exploratory in most trials. Documentation of nuclear medicine tests in this setting awaits the results of properly designed, prospective trials with the standardization of both the nuclear medicine test and endpoints.