bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related quality of life in hospitalized older patients with versus without prolonged use of opioid analgesics, benzodiazepines, and z-hypnotics: a cross-sectional study
Authors: Cheng Socheat , Siddiqui Tahreem Ghazal , Gossop Michael , Stavem Knut , Kristoffersen Espen Saxhaug , Lundqvist Christofer
Published: October 2020

Background

Central nervous system depressant medications (CNSDs) such as opioid analgesics and sedative-hypnotics are commonly prescribed to older patients for the treatment of chronic pain, anxiety and insomnia. Yet, while many studies reported potential harms, it remains unknown whether persistent use of these medications is beneficial for older patients’ self-reported health-related quality of life (HRQoL). The present study clarified this knowledge gap through comparing HRQoL of hospitalized older patients with versus without using CNSD drugs for ≥4 weeks. Moreover, we explored the relationship between such use and HRQoL, adjusting for the effects of polypharmacy, comorbidity burden and other clinically relevant covariates.

Methods

The study was cross-sectional and included 246 older patients recruited consecutively from somatic departments of a large regional university hospital in Norway. We defined prolonged CNSD use as using opioids, benzodiazepines and/or z-hypnotics for ≥4 weeks. Patients’ self-reported HRQoL were measured with scales of the EuroQol EQ-5D-3L instrument. Data analyses were mainly descriptive statistics and regression models.

Results

Patients with prolonged use of CNSDs reported lower scores on both EQ-5D index and EQ VAS compared with those without such use (p < 0.001). They had higher odds of having more problems performing usual activities (OR = 3.37, 95% CI: 1.40 to 8.13), pain/discomfort (OR = 2.06, 95% CI: 1.05 to 4.04), and anxiety/depression (OR = 3.77, 95% CI: 1.82 to 7.82).

In multivariable regression models, there was no significant association between prolonged CNSD use and HRQoL when including pain as a predictor variable. In models not including pain, CNSD use was strongly associated with HRQoL (adjusted for sociodemographic background, polypharmacy, comorbidity, anxiety and depressive symptoms, regression coefficient − 0.19 (95% CI, − 0.31 to − 0.06).

Conclusions

Older patients with prolonged CNSD use reported poorer HRQoL. They also had more pain and higher depression scores. Prolonged use of CNSDs was not independently associated with higher HRQoL.
A tool to evaluate proportionality and necessity in the use of restrictive practices in forensic mental health settings: the DRILL tool (Dundrum restriction, intrusion and liberty ladders)
Authors: Kennedy Harry G. , Mullaney Ronan , McKenna Paul , Thompson John , Timmons David , Gill Pauline , O’Sullivan Owen P. , Braham Paul , Duffy Dearbhla , Kearns Anthony , Linehan Sally , Mohan Damian , Monks Stephen , McLoughlin Lisa , O’Connell Paul , O’Neill Conor , Wright Brenda , O’Reilly Ken , Davoren Mary
Published: October 2020

Background

Prevention of violence due to severe mental disorders in psychiatric hospitals may require intrusive, restrictive and coercive therapeutic practices. Research concerning appropriate use of such interventions is limited by lack of a system for description and measurement. We set out to devise and validate a tool for clinicians and secure hospitals to assess necessity and proportionality between imminent violence and restrictive practices including de-escalation, seclusion, restraint, forced medication and others.

Methods

In this retrospective observational cohort study, 28 patients on a 12 bed male admissions unit in a secure psychiatric hospital were assessed daily for six months. Data on adverse incidents were collected from case notes, incident registers and legal registers. Using the functional assessment sequence of antecedents, behaviours and consequences (A, B, C) we devised and applied a multivariate framework of structured professional assessment tools, common adverse incidents and preventive clinical interventions to develop a tool to analyse clinical practice. We validated by testing assumptions regarding the use of restrictive and intrusive practices in the prevention of violence in hospital. We aimed to provide a system for measuring contextual and individual factors contributing to adverse events and to assess whether the measured seriousness of threating and violent behaviours is proportionate to the degree of restrictive interventions used. General Estimating Equations tested preliminary models of contexts, decisions and pathways to interventions.

Results

A system for measuring adverse behaviours and restrictive, intrusive interventions for prevention had good internal consistency. Interventions were proportionate to seriousness of harmful behaviours. A ‘Pareto’ group of patients (5/28) were responsible for the majority (80%) of adverse events, outcomes and interventions. The seriousness of the precipitating events correlated with the degree of restrictions utilised to safely manage or treat such behaviours.

Conclusion

Observational scales can be used for restrictive, intrusive or coercive practices in psychiatry even though these involve interrelated complex sequences of interactions. The DRILL tool has been validated to assess the necessity and demonstrate proportionality of restrictive practices. This tool will be of benefit to services when reviewing practices internally, for mandatory external reviewing bodies and for future clinical research paradigms.
Content development for a physical activity and sedentary behaviour e-learning module for early childhood education students: a Delphi study
Authors: Bruijns Brianne A. , Johnson Andrew M. , Tucker Patricia
Published: October 2020

Background

Early childhood educators play a prominent role in promoting healthy activity behaviours in childcare. However, they have expressed that they lack the appropriate pre-service training to confidently lead physical activity (PA), and minimize sedentary behaviour (SB), in childcare. As such, the purpose of this Delphi study was to generate and reach agreement on content areas for inclusion in a PA and SB e-Learning module for Early Childhood Education (ECE) students.

Methods

Purposeful sampling of Canadian/international researchers was used to form two expert panels: a PA/SB expert panel (n = 26), and a Canadian ECE panel (n = 35). The PA/SB experts suggested their top 12 PA/SB topics for the module via online survey. These topics were then pooled to generate a list of 19 content areas. In a second online survey, both panels of experts rated the importance of each content area (0 = unimportant to 5 = very important). Mean ratings (M) were ranked separately for each panel, and then ratings were pooled to create an overall ranking of the 19 content areas. Inter-panel agreement of importance rankings was visually represented as a scatterplot and quantified using Spearman’s rho (rs).

Results

The top-rated content area was Outdoor Play (M = 4.77 ± 0.64), followed by Benefits of PA in the Early Years (M = 4.75 ± 0.66), and Factors Influencing PA and SB in Childcare (M = 4.71 ± .74). Monitor PA and Sedentary Time Within Your Classroom had the lowest combined score (M = 3.77 ± 1.44). There was moderate-to strong inter-panel agreement for content area importance rankings (rs = 0.60, 95% CI: 0.20 to 0.83). The majority of the ECE expert panel considered this training important for ECE students (94.3%), aligning with ECE curriculum objectives (91.4%) and accreditation standards (78.8%), and complementary to the present ECE curriculum (88.6%).

Conclusions

Providing PA and SB training to ECE students is a proactive way to ensure healthy movement behaviours are prioritized in childcare programming. With the PA/SB expert-developed content areas, and endorsement by the ECE expert panel, implementing this training within ECE programs is a necessary next step.
Beach boys in Galle, Sri Lanka: multiple HIV risk behaviours and potential for HIV bridging
Authors: Bozicevic Ivana , Manathunge Ariyaratne , Beneragama Sriyakanthi , Gadjaweera Chathrini
Published: October 2020

Background

There are limited data globally on HIV in men who engage in casual and transactional sex with female tourists.

Methods

In 2018 we carried out a respondent-driven sampling (RDS) survey among beach boys in Galle, Sri Lanka, to determine prevalence of HIV and other infections, HIV risk behaviours and utilisation of HIV prevention services. Eligibility criteria included men who cruise in and around beach areas and who had anal and/or vaginal sex with female or male tourists in the 12 months before the survey.

Results

We recruited 373 beach boys. Approximately 49.6% of the participants were married, while 45.7% were single and 4.7% divorced, separated or widowed. A lower percentage of beach boys reported regular partners in the past 12 months (52.3%) compared to casual partners (95.4%). Condom use at last sex with a casual partner was higher (76.7%) compared to condom use with regular partners (58.3%). Condom use at last sex with a tourist was reported by 75.3%. Ever receiving money, goods or services in exchange for sex was reported by 39.7%. For 85.5% of beach boys who sold sex, the last paying partner was a tourist (85.5%) and a woman (82.0%). In the past 12 months before the survey, 32.3% of beach boys paid money for sex, and 99.5% did so from women.

Ever been tested for HIV was reported by 35.3, and 69.1% of those were tested in the 6 months before the survey. In the adjusted multivariate analysis, significant correlates of never testing for HIV were lack of comprehensive knowledge about HIV and unprotected last sexual intercourse with tourists.

The prevalent infections were: HIV, 0.3% (95% CI 0.0–0.4%); syphilis, 0.5% (0.0–1.2%); herpes virus type-2, 5.0% (2.5–7.5%).

Conclusions

There are low level HIV and syphilis prevalence among beach boys in Galle but a high level of sexual risk taking. Beach boys may be acting as a bridge for HIV transmission between higher-risk groups (paying female tourists, men who have sex with men) and lower-risk heterosexual female population in Sri Lanka. More research is needed in South-East Asia on men who trade sexual services to female and male tourists.
Cigarette smoke extract stimulates bronchial epithelial cells to undergo a SUMOylation turnover
Authors: Zhou Haifeng , Zhang Lei , Li Yang , Wu Guorao , Zhu He , Zhang Huilan , Su Jia-Kun , Guo Lei , Zhou Qing , Xiong Fei , Yu Qilin , Yang Ping , Zhang Shu , Cai Jibao , Wang Cong-Yi
Published: October 2020

Background

Chronic obstructive pulmonary disease (COPD) characterized by the airway and lung inflammation, is a leading cause of morbidity and mortality worldwide, especially among smokers over 40 years of age and individuals exposed to biomass smoke. Although the detailed mechanisms of this disease remain elusive, there is feasible evidence that protein posttranslational modifications (PTMs) may play a role in its pathoetiology. We thus conducted studies to dissect the effect of cigarette smoke extracts (CSE) on the change of SUMOylated substrates in human bronchial epithelial cells (HBEs).

Methods

Samples were collected in HBEs with or without 24 h of CSE insult and then subjected to Western-blot and LC-MS/MS analysis. Subsequently, bioinformatic tools were used to analyze the data. The effect of SUMOylation on cytochrome P450 1A1 (CYP1A1) was evaluated by flow cytometry.

Results

It was noted that CSE stimulated HBEs to undergo a SUMOylation turnover as evidenced by the changes of SUMOylated substrates and SUMOylation levels for a particular substrate. The SUMOylated proteins are relevant to the regulation of biological processes, molecular function and cellular components. Particularly, CSE stimulated a significant increase of SUMOylated CYP1A1, a critical enzyme involved in the induction of oxidative stress.

Conclusions

Our data provide a protein SUMOylation profile for better understanding of the mechanisms underlying COPD and support that smoking induces oxidative stress in HBEs, which may predispose to the development of COPD in clinical settings.
Evaluation of lymphocytic infiltration in the bronchial glands of Sjögren’s syndrome in transbronchial lung cryobiopsy
Authors: Okabayashi Hiroko , Baba Tomohisa , Ootoshi Ryota , Shintani Ryota , Tabata Erina , Ikeda Satoshi , Niwa Takashi , Oda Tsuneyuki , Okuda Ryo , Sekine Akimasa , Kitamura Hideya , Komatsu Shigeru , Hagiwara Eri , Takemura Tamiko , Sakagami Takuro , Ogura Takashi
Published: October 2020

Background

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by deteriorated exocrine gland function with associated lymphocytic infiltration. However, there are few pathological studies on bronchial glands in SS. In this study, we aimed to clarify pathological features of bronchial glands in SS.

Methods

We retrospectively evaluated infiltration of lymphocytes in the bronchial glands incidentally collected by transbronchial lung cryobiopsy (TBLC), which were performed for the diagnosis of diffuse lung diseases. The degrees of lymphocyte infiltration in the bronchial glands were classified into four grades (grade 0–3). We compared the degrees of infiltration of SS with those of other diffuse lung diseases.

Results

TBLC for diagnosis of diffuse lung diseases were performed on 432 cases during the study period. The samples of 50 cases included bronchial glands. Of those, 20 cases were excluded due to insufficient size or influence of therapy. The remaining 30 cases included 17 of idiopathic interstitial pneumonias, 5 of chronic hypersensitivity pneumonia, 6 of connective tissue disease (SS; n = 4, systemic sclerosis; n = 1, dermatomyositis; n = 1) and 2 of other diseases. In SS, infiltration of lymphocytes was observed in all cases; grade 1 in one, grade 2 in one, and grade 3 in two cases. In contrast, 11 of 26 in other diseases showed no lymphocytes infiltration, with the remaining 15 of grade 1 infiltration. Grade 2 or more infiltration were found only in SS but not in other diseases.

Conclusion

Our results suggested that high-grade lymphocytic infiltration of bronchial glands is a distinct characteristics in SS.
IL-32 induces epithelial-mesenchymal transition by triggering endoplasmic reticulum stress in A549 cells
Authors: Gong Ling , Liu Gang , Zhu Honglan , Li Caihong , Li Pengmei , Liu Changlu , Tang Hongbo , Wu Kaifeng , Wu Jie , Liu Daishun , Tang Xiaoping
Published: October 2020

Background

Epithelial-mesenchymal transition (EMT) is a key process in the onset and development of idiopathic pulmonary fibrosis (IPF) with unclear mechanisms. Our previous studies found that bleomycin and tunicamycin could induce ER stress and consequently trigger EMT accompanying with IL-32 overexpression. This study was aimed to investigate the effects of IL-32 on EMT and ER stress to elucidate the pathogenesis of IPF.

Methods

Human lung adenocarcinoma A549 cells were treated with recombinant human (rh)IL-32, IL-32 siRNA and EMT inducer tunicamycin, or 4-phenylbutyric acid (4-PBA), respectively. Then the cell morphology was observed and the expression of ER-related markers and EMT-related markers were detected by RT-qPCR or western blotting.

Results

Stimulation of A549 cells with rhIL-32 led to a morphological change from a pebble-like shape to an elongated shape in a portion of the cells, accompanied by down regulated expression of the epithelial cell marker E-cadherin and up regulated expression of the mesenchymal cell markers N-cadherin, Vimentin, and Zeb-1. However, these rhIL-32 induced changes were inhibited by the ER stress inhibitor 4-PBA. Suppression of IL-32 expression with siRNA inhibited TM-induced EMT. Further stimulation of the A549 cells with rhIL-32 demonstrated an increase in the expression of GRP78, although this increase was also inhibited by 4-PBA.

Conclusions

These results suggest that IL-32 induces EMT in A549 cells by triggering ER stress, and IL-32 may be a novel marker for IPF.
LUMINOUS database: lumbar multifidus muscle segmentation from ultrasound images
Authors: Belasso Clyde J. , Behboodi Bahareh , Benali Habib , Boily Mathieu , Rivaz Hassan , Fortin Maryse
Published: October 2020

Background

Among the paraspinal muscles, the structure and function of the lumbar multifidus (LM) has become of great interest to researchers and clinicians involved in lower back pain and muscle rehabilitation. Ultrasound (US) imaging of the LM muscle is a useful clinical tool which can be used in the assessment of muscle morphology and function. US is widely used due to its portability, cost-effectiveness, and ease-of-use. In order to assess muscle function, quantitative information of the LM must be extracted from the US image by means of manual segmentation. However, manual segmentation requires a higher level of training and experience and is characterized by a level of difficulty and subjectivity associated with image interpretation. Thus, the development of automated segmentation methods is warranted and would strongly benefit clinicians and researchers. The aim of this study is to provide a database which will contribute to the development of automated segmentation algorithms of the LM.

Construction and content

This database provides the US ground truth of the left and right LM muscles at the L5 level (in prone and standing positions) of 109 young athletic adults involved in Concordia University’s varsity teams. The LUMINOUS database contains the US images with their corresponding manually segmented binary masks, serving as the ground truth. The purpose of the database is to enable development and validation of deep learning algorithms used for automatic segmentation tasks related to the assessment of the LM cross-sectional area (CSA) and echo intensity (EI). The LUMINOUS database is publicly available at http://data.sonography.ai.

Conclusion

The development of automated segmentation algorithms based on this database will promote the standardization of LM measurements and facilitate comparison among studies. Moreover, it can accelerate the clinical implementation of quantitative muscle assessment in clinical and research settings.
“Got to build that trust”: the perspectives and experiences of Aboriginal health staff on maternal oral health
Authors: Kong Ariana C. , Sousa Mariana S. , Ramjan Lucie , Dickson Michelle , Goulding Joanne , Gwynne Kylie , Talbot Folau , Jones Nathan , Srinivas Ravi , George Ajesh
Published: October 2020

Background

In Australia, models of care have been developed to train antenatal care providers to promote oral health among pregnant women. However, these models are underpinned by Western values of maternity care that do not consider the cultural needs of Aboriginal and Torres Strait Islander women. This study aimed to explore the perceptions and experiences of Aboriginal health staff towards oral health care during pregnancy. It is part of a larger program of research to develop a new, culturally safe model of oral health care for Aboriginal women during pregnancy.

Methods

A descriptive qualitative methodology informed the study. Focus groups were convened to yarn with Aboriginal Health Workers, Family Partnership Workers and Aboriginal management staff at two antenatal health services in Sydney, Australia.

Results

A total of 14 people participated in the focus groups. There were four themes that were constructed. These focused on Aboriginal Health Workers and Family Partnership Workers identifying their role in promoting maternal oral health, where adequate training is provided and where trust has been developed with clients. Yet, because the Aboriginal health staff work in a system fundamentally driven by the legacy of colonisation, it has significantly contributed to the systemic barriers Aboriginal pregnant women continue to face in accessing health services, including dental care. The participants recommended that a priority dental referral pathway, that supported continuity of care, could provide increased accessibility to dental care.

Conclusions

The Aboriginal health staff identified the potential role of Aboriginal Health Workers and Family Partnership Workers promoting oral health among Aboriginal pregnant women. To develop an effective oral health model of care among Aboriginal women during pregnancy, there is the need for training of Aboriginal Health Workers and Family Partnership Workers in oral health. Including Aboriginal staff at every stage of a dental referral pathway could reduce the fear of accessing mainstream health institutions and also promote continuity of care. Although broader oral health policies still need to be changed, this model could mitigate some of the barriers between Aboriginal women and both dental care providers and healthcare systems.
Investigating effects of preoperative inflammatory biomarkers on predicting survival outcomes of intrahepatic cholangiocarcinoma after curative resection
Authors: Zhang Zeyu , Zhou Yufan , Hu Kuan , Huang Yun
Published: October 2020

Introduction

Intrahepatic cholangiocarcinoma (ICC) stands as the second most common malignant tumor in the liver with poor patient prognosis. Increasing evidences have shown that inflammation plays a significant role in tumor progression, angiogenesis, and metastasis. However, the prognosis significance of inflammatory biomarkers on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is poorly recognized.

Methods

ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), were investigated.

Results

Receiver operating characteristic (ROC) curves showed no significance in NLR, PLR, and LMR in RFS and OS, while significant results were shown on SII in both RFS (P = 0.035) and OS (P = 0.034) with areas under ROC curve as 0.63 (95%CI 0.52–0.74) and 0.62 (95%CI 0.51–0.72), respectively. Kaplan-Meier curves revealed a statistically significant better survival data in SII-low groups on both RFS (P < 0.001) and OS (P < 0.001). The univariate and multivariate analyses revealed that higher level of SII was independently associated with both poorer RFS time and OS time. However, no significant result was shown on NLR, PLR, or LMR.

Conclusion

SII is an effective prognostic factor for predicting the prognosis of ICC patient undergone curative hepatectomy, while NLR, PLR, and LMR are not associated with clinical outcomes of these patients.
Efficient control of Japanese encephalitis virus in the central nervous system of infected pigs occurs in the absence of a pronounced inflammatory immune response
Authors: Redant Valerie , Favoreel Herman W. , Dallmeier Kai , Van Campe Willem , De Regge Nick
Published: October 2020

Background

Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia. JEV infection of mice and humans can lead to an uncontrolled inflammatory response in the central nervous system (CNS), resulting in a detrimental outcome. Pigs act as important amplification and reservoir hosts, and JEV infection of pigs is mostly subclinical. Information on virus spread in the CNS and immune responses controlling JEV infection in the CNS of pigs, however remains scarce.

Methods

Nine-week-old pigs were inoculated intranasal or intradermal with a relevant dose of 105 TCID50 of JEV genotype 3 Nakayama strain. Clinical signs were assessed daily, and viral spread was followed by RT-qPCR. mRNA expression profiles were determined to study immune responses in the CNS.

Results

Besides a delay of 2 days to reach the peak viremia upon intranasal compared to intradermal inoculation, the overall virus spread via both inoculation routes was highly similar. JEV appearance in lymphoid and visceral organs was in line with a blood-borne JEV dissemination. JEV showed a particular tropism to the CNS but without the induction of neurological signs. JEV entry in the CNS probably occurred via different hematogenous and neuronal pathways, but replication in the brain was mostly efficiently suppressed and associated with a type I IFN-independent activation of OAS1 expression. In the olfactory bulb and thalamus, where JEV replication was not completely controlled by this mechanism, a short but strong induction of chemokine gene expression was detected. An increased IFNy expression was simultaneously observed, probably originating from infiltrating T cells, correlating with a fast suppression of JEV replication. The chemokine response was however not associated with the induction of a strong inflammatory response, nor was an induction of the NLRP3 inflammasome observed.

Conclusions

These findings indicate that an adequate antiviral response and an attenuated inflammatory response contribute to a favorable outcome of JEV infection in pigs and help to explain the limited neurological disease compared to other hosts. We show that the NLRP3 inflammasome, a key mediator of neurologic disease in mice, is not upregulated in pigs, further supporting its important role in JEV infections.
Spinal neuronal excitability and neuroinflammation in a model of chemotherapeutic neuropathic pain: targeting the resolution pathways
Authors: Meesawatsom Pongsatorn , Hathway Gareth , Bennett Andrew , Constantin-Teodosiu Dumitru , Chapman Victoria
Published: October 2020

Background

Neuroinflammation is a critical feature of sensitisation of spinal nociceptive processing in chronic pain states. We hypothesised that the resolvin pathways, a unique endogenous control system, may ameliorate aberrant spinal processing of somatosensory inputs associated with chemotherapy-induced neuropathic pain (CINP).

Method

The paclitaxel (PCX) model of CINP was established in male Sprague-Dawley rats and compared to control rats (n = 23 and 22, respectively). Behavioural pain responses were measured, and either single unit electrophysiological recordings of dorsal horn wide dynamic range (WDR) neurones were performed, or mRNA microarray analysis of the dorsal horn of the spinal cord was undertaken.

Results

PCX rats exhibited significant changes in behavioural responses to mechanical and cold stimuli. A higher proportion of WDR neurones in PCX rats were polymodal (generating post-discharge following a non-noxious mechanical stimulus, responding to non-noxious cold and exhibiting spontaneous activity) compared to control (p < 0.05). Microarray analysis revealed changes in proinflammatory pathways (Tlr, Tnfrsf1a, Nlrp1a, Cxcr1, Cxcr5, Ccr1, Cx3cr1) and anti-inflammatory lipid resolvin pathways (Alox5ap, Cyp2j4 and Ptgr1) compared to control (p < 0.05). Ingenuity pathway analysis predicted changes in glutamatergic and astrocyte signaling in the PCX group. Activation of the resolvin system via the spinal administration of aspirin-triggered resolvin D1 (AT-RvD1) markedly inhibited (73 ± 7% inhibition) normally non-noxious mechanically (8 g) evoked responses of WDR neurones only in PCX rats, whilst leaving responses to noxious mechanically induced stimuli intact. Inhibitory effects of AT-RvD1were comparable in magnitude to spinal morphine (84 ± 4% inhibition).

Conclusion

The PCX model of CINP was associated with mechanical allodynia, altered neuronal responses and dysregulation of pro- and anti-inflammatory signalling in the spinal dorsal horn. The resolvin AT-RvD1 selectively inhibited low weight mechanical-evoked responses of WDR neurones in PCX rats, but not in controls. Our data support the targeting of spinal neuroinflammation via the activation of the resolvin system as a new therapeutic approach for CINP.
The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease
Authors: McCarthy Micheline , Raval Ami P.
Published: October 2020

The peri-menopause or menopausal transition—the time period that surrounds the final years of a woman’s reproductive life—is associated with profound reproductive and hormonal changes in a woman’s body and exponentially increases a woman’s risk of cerebral ischemia and Alzheimer’s disease. Although our understanding of the exact timeline or definition of peri-menopause is limited, it is clear that there are two stages to the peri-menopause. These are the early menopausal transition, where menstrual cycles are mostly regular, with relatively few interruptions, and the late transition, where amenorrhea becomes more prolonged and lasts for at least 60 days, up to the final menstrual period. Emerging evidence is showing that peri-menopause is pro-inflammatory and disrupts estrogen-regulated neurological systems. Estrogen is a master regulator that functions through a network of estrogen receptors subtypes alpha (ER-α) and beta (ER-β). Estrogen receptor-beta has been shown to regulate a key component of the innate immune response known as the inflammasome, and it also is involved in regulation of neuronal mitochondrial function. This review will present an overview of the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation, plus regulation of the innate immune response by ER-β-mediated mechanisms.
Infertility policy analysis: a comparative study of selected lower middle- middle- and high-income countries
Authors: Morshed-Behbahani Bahar , Lamyian Minoor , Joulaei Hassan , Rashidi Batool Hossein , Montazeri Ali
Published: October 2020

Background

Infertility has recently become a salient but neglected global issue. Policies to address the sexual and reproductive health and rights (SRHR) are vital, especially in lower middle and middle-income countries (LMICs). Hence, the aim of this study was to compare the national infertility policies in the selected countries (LMICs comparing with high-income) to determine gaps or to confirm desirable policies in the given health systems.

Methods

This study has executed a comparative policy analysis of infertility services using the universal health coverage framework (financial protection, population coverage, and service features) in three scopes (prevention, treatment, and supportive care). Seven countries that had infertility programs in their health sectors were selected.

Results

The results showed that financial protection was good in high and middle-income countries, but in a lower middle income, and in one high-income country was poor. The findings also showed that health systems in the same countries had no infertility services for men. Preventive and supportive care services were neglected in LMICs by governments.

Conclusion

The findings indicate that income is not the only factor that fulfills universal health coverage for infertility care services. Perhaps to achieve equity in infertility care services, it should be seen as a universal human right to accomplish the right to have a child and to have a life with physical and mental health for all men and women.
Detection and stage classification of Plasmodium falciparum from images of Giemsa stained thin blood films using random forest classifiers
Authors: Abbas Syed Saiden , Dijkstra Tjeerd M. H.
Published: October 2020

Background

The conventional method for the diagnosis of malaria parasites is the microscopic examination of stained blood films, which is time consuming and requires expertise. We introduce computer-based image segmentation and life stage classification with a random forest classifier. Segmentation and stage classification are performed on a large dataset of malaria parasites with ground truth labels provided by experts.

Methods

We made use of Giemsa stained images obtained from the blood of 16 patients infected with Plasmodium falciparum. Experts labeled the parasite types from each of the images. We applied a two-step approach: image segmentation followed by life stage classification. In segmentation, we classified each pixel as a parasite or non-parasite pixel using a random forest classifier. Performance was evaluated with classification accuracy, Dice coefficient and free-response receiver operating characteristic (FROC) analysis. In life stage classification, we classified each of the segmented objects into one of 8 classes: 6 parasite life stages, early ring, late ring or early trophozoite, mid trophozoite, early schizont, late schizont or segmented, and two other classes, white blood cell or debris.

Results

Our segmentation method gives an average cross-validated Dice coefficient of 0.82 which is a 13% improvement compared to the Otsu method. The Otsu method achieved a True Positive Fraction (TPF) of 0.925 at the expense of a False Positive Rate (FPR) of 2.45. At the same TPF of 0.925, our method achieved an FPR of 0.92, an improvement by more than a factor two. We find that inclusion of average intensity of the whole image as feature for the random forest considerably improves segmentation performance. We obtain an overall accuracy of 58.8%when classifying all life stages. Stages are mostly confused with their neighboring stages. When we reduce the life stages to ring, trophozoite and schizont only, we obtain an accuracy of 82.7%.

Conclusion

Pixel classification gives better segmentation performance than the conventional Otsu method. Effects of staining and background variations can be reduced with the inclusion of average intensity features. The proposed method and data set can be used in the development of automatic tools for the detection and stage classification of malaria parasites. The data set is publicly available as a benchmark for future studies.
Gastric adenocarcinoma of the fundic gland type: clinicopathological features of eight patients treated with endoscopic submucosal dissection
Authors: Li Chengfang , Wu Xinglong , Yang Shuang , Yang Xiaorong , Yao Jin , Zheng Hong
Published: October 2020

Background

Gastric adenocarcinoma of the fundic gland type (GA-FG) has been added to the 2019 edition of the World Health Organization’s list of digestive system-associated cancers. This lesion differentiates toward the fundic gland and mostly involves chief cell-predominant differentiation with low-grade cytology. Clinicians and pathologists are still unaware of this rare disease; consequently, some cases are incorrectly diagnosed. This study aimed to investigate the clinicopathological features of GA-FG using retrospective analyses of endoscopic and pathological findings.

Materials and methods

Samples were collected from patients diagnosed with GA-FG. The clinical courses of all patients were monitored prospectively and reviewed retrospectively. Available clinical information, endoscopic features, pathological appearance, and follow-up data were assessed. Immunohistochemistry [mucin (MUC) 2, MUC5, MUC6, P53, CDX2, Ki67, SYN, CD56, CGA, β-catenin, and pepsinogen-I] was examined using Envision two-step method.

Results

Eight cases of endoscopic submucosal dissection (ESD) were obtained from our institution. Patient age ranged from 48 to 80 years (mean, 65 years). Some patients were on acid-suppressing medication. Most lesions were located in the upper third (n = 7) and one was in the middle third of the stomach. Six lesions were of the superficial flat type, whereas two were of the superficial elevated type. Narrow-band imaging using magnifying endoscopy showed irregular microvascular patterns (MVPs) in four cases and regular MVPs in the remaining cases. All lesions were primarily solitary and ~ 6 mm in diameter (largest, 12 mm). The main body of the tumors were localized in the mucosal layer, of which six cases invade into the submucosal layer. Well-formed glands of chief cells were predominant. Tumor cells were positive for pepsinogen-I, MUC6, SYN, and CD56. Lymphatic and vascular infiltration and metastatic and recurrent disease were not observed in any case.

Conclusion

GA-FG, a well-differentiated adenocarcinoma with mild atypia, can be completely removed using ESD, with a favorable prognosis in patients.
Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking
Authors: Li Jialin , Luo Hua , Liu Xinkui , Zhang Jingyuan , Zhou Wei , Guo Siyu , Chen Xiuping , Liu Yingying , Jia Shanshan , Wang Haojia , Li Bingbing , Cheng Guoliang , Wu Jiarui
Published: October 2020

Background

Yuzhi Zhixue Granule (YZG) is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG.

Methods

The active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein–protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules.

Results

The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds.

Conclusion

This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.
Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer—results from the randomized phase III SUCCESS-A trial
Authors: de Gregorio Amelie , Häberle Lothar , Fasching Peter A. , Müller Volkmar , Schrader Iris , Lorenz Ralf , Forstbauer Helmut , Friedl Thomas W. P. , Bauer Emanuel , de Gregorio Nikolaus , Deniz Miriam , Fink Visnja , Bekes Inga , Andergassen Ulrich , Schneeweiss Andreas , Tesch Hans , Mahner Sven , Brucker Sara Y. , Blohmer Jens-Uwe , Fehm Tanja N. , Heinrich Georg , Lato Krisztian , Beckmann Matthias W. , Rack Brigitte , Janni Wolfgang
Published: October 2020

Background

When chemotherapy is indicated in patients with early breast cancer, regimens that contain anthracyclines and taxanes are established standard treatments. Gemcitabine has shown promising effects on the response and prognosis in patients with metastatic breast cancer. The SUCCESS-A trial (NCT02181101) examined the addition of gemcitabine to a standard chemotherapy regimen in high-risk early breast cancer patients.

Methods

A total of 3754 patients with at least one of the following characteristics were randomly assigned to one of the two treatment arms: nodal positivity, tumor grade 3, age ≤ 35 years, tumor larger than 2 cm, or negative hormone receptor status. The treatment arms received either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel (FEC → Doc); or three cycles of FEC followed by three cycles of docetaxel and gemcitabine (FEC → Doc/Gem). The primary study aim was disease-free survival (DFS), and the main secondary objectives were overall survival (OS) and safety.

Results

No differences were observed in the 5-year DFS or OS between FEC → Doc and FEC → Doc/Gem. The hazard ratio was 0.93 (95% CI, 0.78 to 1.12; P = 0.47) for DFS and 0.94 (95% CI, 0.74 to 1.19; P = 0.60) for OS. For patients treated with FEC → Doc and FEC → Doc/Gem, the 5-year probabilities of DFS were 86.6% and 87.2%, and the 5-year probabilities of OS were 92.8% and 92.5%, respectively.

Conclusion

Adding gemcitabine to a standard chemotherapy does not improve the outcomes in patients with high-risk early breast cancer and should therefore not be included in the adjuvant treatment setting.

Trial registration

Clinicaltrials.gov NCT02181101 and EU Clinical Trials Register EudraCT 2005-000490-21. Registered September 2005.
A new blind color watermarking based on a psychovisual model
Authors: Lefevre Pascal , Alleysson David , Carre Philippe
Published: October 2020

In this paper, we address the problem of the use of a human visual system (HVS) model to improve watermark invisibility. We propose a new color watermarking algorithm based on the minimization of the perception of color differences. This algorithm is based on a psychovisual model of the dynamics of cone photoreceptors. We used this model to determine the discrimination power of the human for a particular color and thus the best strategy to modify color pixels. Results were obtained on a color version of the lattice quantization index modulation (LQIM) method and showed improvements on psychovisual invisibility and robustness against several image distortions.
Design of a culture medium for optimal growth of the bacterium Pseudoxanthomonas indica H32 allowing its production as biopesticide and biofertilizer
Authors: Morales-Borrell Dayana , González-Fernández Nemecio , Mora-González Néstor , Pérez-Heredia Carlos , Campal-Espinosa Ana , Bover-Fuentes Eddy , Salazar-Gómez Eladio , Morales-Espinosa Yissel
Published: October 2020

Culture medium composition is one of the most important parameters to analyze in biotechnological processes with industrial purposes. The aim of this study was to design of a culture medium for optimal growth of the bacterium Pseudoxanthomonas indica H32 allowing its production as biopesticide and biofertilizer. The influence of several carbon and nitrogen sources and their molar ratios on P. indica H32 growth was investigated. The effect of different micronutrients such as mineral salts and vitamin on P. indica H32 growth was determined as well. A mixture design based on Design-Expert 10.0 Software was performed to optimize the culture medium concentration. Finally, in the designed medium, an attribute of the biological mechanism of action of the P. indica H32 against nematodes, was evaluated: the hydrogen sulfide production. It was found that tested carbon/nitrogen ratios were not a significant influence on P. indica H32 growth. Growth of P. indica H32 was favored with use of sucrose, yeast extract and phosphate buffer without the addition of any tested micronutrients. An optimal concentration of 10 g/L sucrose and 5 g/L yeast extract were obtained at a cost of 0.10 $/L. In this concentration, the specific growth rate (µ) and maximal optical density (Xmax) were equal to 0.439 h− 1 and 8.00 respectively. It was evidenced that under the culture conditions used, P. indica H32 produced hydrogen sulfide. The designed medium led to a 1.08 $/L reduction of costs in comparison to LB medium. These results were critical to carry on with biotechnological development of P. indica H32 as a bioproduct.
Validation of the DECA criteria for allergic conjunctivitis severity and control
Authors: Sánchez-Hernández M. Cesárea , Navarro Ana M. , Colás Carlos , del Cuvillo Alfonso , Sastre Joaquín , Mullol Joaquim , Valero Antonio
Published: October 2020

Background

Allergic conjunctivitis (AC) is usually associated to allergic rhinitis (AR), but the severity and control of ocular symptoms should be assessed independently to improve diagnosis and treatment. The criteria from the Spanish consensus document on allergic conjunctivitis (DECA) aimed to be used as a patient-reported instrument for AC management. Here we validate these criteria for classifying AC severity and defining its control following COSMIN guidelines recommendations.

Methods

Patients with moderate or severe AR [reflective total nasal symptom score (rTNSS) score ≥ 8] and concomitant AC were recruited from hospitals in Spain. Patients were classified according to the severity of ocular symptoms as mild, moderate, or severe, and classified with respect to control as controlled and non-controlled, using the DECA criteria. To validate these criteria, comparisons with the validated modified allergic rhinitis and its impact on asthma (mARIA), reflective total ocular symptom score (rTOSS), rhinitis control assessment test (RCAT), ESPRINT-15 questionnaires, a conjunctival hyperemia scale and a visual analogue scale (VAS) for ocular symptoms were performed.

Results

A total of 128 patients participated in the validation. Mean age was 34.4 ± 12.1 years; 72.7% were women. The DECA criteria showed a good discriminant validity, reflecting a high capacity to differentiate between mild, moderate, and severe patients, and controlled from uncontrolled patients. A strong association between AC and AR was reflected in the comparison between the DECA and the mARIA criteria (p < 0.0001). The DECA criteria for severity and control presented satisfactory properties for longitudinal validity and responsiveness.

Conclusions

Validation of the DECA criteria for severity and control of AC suggested that it can be useful in the evaluation of eye symptoms and follow-up of therapies.
Normalized solutions for a coupled fractional Schrödinger system in low dimensions
Authors: Li Meng , He Jinchun , Xu Haoyuan , Yang Meihua
Published: October 2020

We consider the following coupled fractional Schrödinger system: $$ \textstyle\begin{cases} (-\Delta )^{s}u+\lambda _{1}u=\mu _{1} \vert u \vert ^{2p-2}u+ \beta \vert v \vert ^{p} \vert u \vert ^{p-2}u, \\ (-\Delta )^{s}v+\lambda _{2}v=\mu _{2} \vert v \vert ^{2p-2}v+\beta \vert u \vert ^{p} \vert v \vert ^{p-2}v \end{cases}\displaystyle \quad \text{in } {\mathbb{R}^{N}}, $$

{

(
−
Δ
)

s

u
+

λ
1

u
=

μ
1

|
u

|

2
p
−
2

u
+
β
|
v

|
p

|
u

|

p
−
2

u
,

(
−
Δ
)

s

v
+

λ
2

v
=

μ
2

|
v

|

2
p
−
2

v
+
β
|
u

|
p

|
v

|

p
−
2

v

in 

R
N

,
with $0< s<1$
0
<
s
<
1
, $2s< N\le 4s$
2
s
<
N
≤
4
s
and $1+\frac{2s}{N}< p<\frac{N}{N-2s}$
1
+

2
s

N

<
p
<

N

N
−
2
s

, under the following constraint: $$ \int _{\mathbb{R}^{N}} \vert u \vert ^{2}\,dx=a_{1}^{2} \quad \text{and}\quad \int _{ \mathbb{R}^{N}} \vert v \vert ^{2}\,dx=a_{2}^{2}. $$

∫

R
N

|
u

|
2

d
x
=

a

1

2

and

∫

R
N

|
v

|
2

d
x
=

a

2

2

.
Assuming that the parameters $\mu _{1}$

μ
1

, $\mu _{2}$

μ
2

, $a_{1}$

a
1

, $a_{2}$

a
2

are fixed quantities, we prove the existence of normalized solution for different ranges of the coupling parameter $\beta >0$
β
>
0
.
A new fourth-order explicit group method in the solution of two-dimensional fractional Rayleigh–Stokes problem for a heated generalized second-grade fluid
Authors: Khan Muhammad Asim , Ali Norhashidah Hj. Mohd , Hamid Nur Nadiah Abd
Published: October 2020

In this article, a new explicit group iterative scheme is developed for the solution of two-dimensional fractional Rayleigh–Stokes problem for a heated generalized second-grade fluid. The proposed scheme is based on the high-order compact Crank–Nicolson finite difference method. The resulting scheme consists of three-level finite difference approximations. The stability and convergence of the proposed method are studied using the matrix energy method. Finally, some numerical examples are provided to show the accuracy of the proposed method.