bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of daily versus weekly service of infectious diseases consultation on hospital antimicrobial consumption: a retrospective study
Authors: Cona Andrea , Gazzola Lidia , Viganò Ottavia , Bini Teresa , Marchetti Giulia Carla , Monforte Antonella d'Arminio
Published: August 2020

Background: To verify whether daily service of Infectious Diseases consultation (ID-cons) is more effective than weekly service in reducing antibiotic (ABT) consumption without worsening of clinical outcomes. Methods: Two-years observational analysis of all the ID-cons provided in a hospital in Milan. ID-cons resulted in: start-of-ABT; no-ABT; confirmation; modification-of-ABT. We evaluated the impact of weekly (09/2016-09/2017) versus daily (10/2017-10/2018) service of ID-cons on: time-from-admission-to-first-ID-cons, type of ABT-intervention and number-of-ID-cons per 100 bed days (bd). Primary outcomes: (i) reduction of overall hospital ABT consumption and (ii) reduction of ABT consumption by department and by ABT classes expressed as defined-daily-dose (DDD)/100bd (by Wilcoxon test for paired data). Secondary outcome: no significant increment of overall and sepsis-related in-hospital mortality (as death/patient’s admissions) from 2017 to 2018. Results: Overall 2552 ID-cons in 1111 patients (2.3 ID-cons/patient) were performed (18.6% weekly vs 81.4% daily). No differences in patient’s characteristics were observed. In daily-service, compared to weekly, patients were seen by the ID-consultant earlier (time-from-admission-to-ID-cons: 6 days (IQR 2-13) vs 10 days (IQR 6-19), p<0.0001) and ABT was more often started by the ID-consultant (Start-of-ABT: 11.6% vs 8%, p=0.02). After switch to daily service, the number-of-ID-cons increased from 0.4/100bd to 1.5/100bd (p=0.01), with the greatest increase in the emergency department (1.5/100bd vs 6.7/100bd, p<0.0001). Total ABT consumption decreased from 62.1 to 59.3 DDD/100bd, p=0.02. As for the number-of-cons, the consumption of ABT decreased mainly in the emergency area. According to ABT classes, glycopeptides consumption has been reduced from 3.1 to 2.1 DDD/100bd (p=0.02) while carbapenem use decreased from 3.7 to 3.1 DDD/100bd (p=0.07). No changes in overall-mortality (5.2% vs 5.2%) and sepsis-related mortality (19.3% vs 20.9%; p=0.7) were observed among the two time-period. Conclusions: Daily-ID-cons resulted in a more comprehensive taking charge of the infected patient by the ID-consultant, especially in the emergency area where we also observed the highest rate of reduction of ABT-usage. No change in mortality was observed.
COVID-19 Epidemic Prevention Plan: Reducing the Operational Risk in Pharmacy by the Isolation and Triage Mechanism
Authors: Wang Ya-Ling , Lu Ying-Hao , Lee Li-Yao , Kuo Chen-Chun , Shen Mei-Chiu , Chung Tang-Chia , Hsu Yu-Sheng , Lee Chun-Chen , Wang Jia-Hong , Hung Ching-Tzu
Published: August 2020

Background: Taiwan medical centers mainly use "Central Pharmacy" to carry out pharmaceutical operations and human resources management. The pharmacy is a 24-hour medication supply center for all units in the Hospital. Therefore, how to make the pharmacy run continuously in the potential impact of COVID-19 pandemic is an important issue in the epidemic prevention of the medical center. The purpose of this study is to design to reduce the incidence of cross or cluster infection in the event of nosocomial infection and to maintain the continuous operation of pharmaceutical service.Methods: The planning of "isolation and triage" of pharmaceutical operations is based on the epidemic level of COVID-19, the closing situation of outpatient service, the number of outpatients receiving medicine service and the number of inpatient beds.Results: After the overall planning, in the case of the low epidemic level (level A1), the emergency pharmacy took advance deployment, and fixed personnel was assigned to work in fixed location in the isolation, while other units started the isolation mode in the case of the moderate epidemic level (level B). Grouping mode was added for the severe epidemic level (level C). Different management measures should be planned according to the different level of risk area evaluated by the infection control center.Conclusions: In this study, the risk reduction management mechanism of "isolation and triage" was effectively used to make proper manpower allocation and work planning for all pharmaceutical service in Hospital.
Frequent avoidable admissions amongst Aboriginal and non-Aboriginal people with chronic disease in New South Wales, Australia: a retrospective cohort study
Authors: Jayakody Amanda Anne , Oldmeadow Christopher , Carey Mariko , Bryant Jamie , Evans Tiffany , Ella Stephen , Attia John , Towle Simon , Sanson-Fisher Robert
Published: August 2020

Background: Aboriginal and Torres Strait Islander people have high rates of avoidable hospital admissions for chronic diseases, however little is known about the frequency of avoidable admissions for this population. This study aimed to examine trends in avoidable admissions among Aboriginal and non-Aboriginal people with ambulatory care sensitive chronic conditions in New South Wales (NSW), Australia. Methods: A retrospective cohort analysis using de-identified linked administrative data of Aboriginal and non-Aboriginal patients between 2005/06 to 2013/14. Eligible patients were admitted to a NSW public hospital and who had one or more of the following ambulatory care sensitive chronic conditions as a principal diagnosis: diabetic complications, asthma, angina, hypertension, congestive heart failure and/or chronic obstructive pulmonary disease. The primary outcomes were the number of avoidable admissions for an individual in each financial year, and whether an individual had three or more admissions compared with one to two avoidable admissions in each financial year. Poisson and logistic regression models and a test for differences in yearly trends were used to assess the frequency of avoidable admissions over time, adjusting for sociodemographic variables and restricted to those aged ≤75 years.Results: There were a total of 27,467 avoidable admissions corresponding to 19,025 patients over the nine-year period (71.2% Aboriginal; 28.8% non-Aboriginal). Aboriginal patients were 15% more likely than non-Aboriginal patients to have a higher number of avoidable admissions per financial year (IRR=1.15; CI: 1.11, 1.20). Aboriginal patients were almost twice as likely as non-Aboriginal patients to experience three or more avoidable admissions per financial year (OR=1.90; CI=1.60, 2.26). There were no significant differences between Aboriginal and non-Aboriginal people in yearly trends for either the number of avoidable admissions, or whether or not an individual experienced three or more avoidable admissions per financial year (p=0.8599; 0.8608 respectively). Conclusion: Aboriginal people were significantly more likely to experience frequent avoidable admissions over a nine-year period compared to non-Aboriginal people. These high rates reflect the need for further research into which interventions are able to successfully reduce avoidable admissions among Aboriginal people with chronic diseases, and the importance of culturally appropriate early prevention and community health care.
Genetic and Clinical Phenotypic Analysis of Familial Stapes Sclerosis Caused by a NOG Mutation
Authors: Yu Rong , JIANG HONGQUN , LUO WU GEN
Published: August 2020

Background：Noggin protein encoded by NOG gene can interfere with the binding of bone morphogenetic protein to its receptor, thus affecting bone and joint develop pment. The symptoms include abnormal skeletal development and conductive deaf ness Methods: In a Retrospective study, clinical data of the proband and her family members include 8 people and 50 healthy normal controls were collected. Secon d-generation sequencing were performed on peripheral blood samples from them. Results：The sequencing analysis indicated that, in the probrand, the NOG gene included c.532T>C (cytosine deletion), leading to an amino acid change. The prob and's father, grandmother, second sister, and third sister also had this mutation, whereas those with normal phenotypes did not have the mutation. Conclusion：Analysis of this family showed that the new presentation of c.532T>C mutation in the NOG gene resulted in syndrome-type autosomal dominant inheritan ce reflected in a mild clinical phenotype, which is of great significance for further studies of the clinical phenotype and pathogenesis of stapetectopia.
The Burden of Anxiety During the COVID-19 Pandemic Among People Living with HIV (PLHIV) in Pune, India
Authors: Marbaniang Ivan , Sangle Shashikala , Nimkar Smita , Zarekar Kanta , Salvi Sonali , Chavan Amol , Gupta Amita , Suryavanshi Nishi , Mave Vidya
Published: August 2020

Introduction: There is a dearth of data on anxiety related to the COVID-19 pandemic from people living with HIV (PLHIV). This is a cause of concern as anxiety is associated with antiretroviral therapy (ART) nonadherence. Globally, India has the third largest population of PLHIV and third highest number of COVID-19 cases which are rapidly increasing. Therefore, it is crucial to understand the burden of anxiety and its sources among Asian Indian PLHIV during this pandemic.Methods: We used data from a telephonically delivered assessment among PLHIV engaged in care at a tertiary healthcare associated antiretroviral therapy (ART) center in Pune, India. Assessments were conducted between April 21 and May 28, 2020, one month into the government mandated lockdown. GAD-7 was used to assess for anxiety over two-preceding weeks. Significant sociodemographic and clinical differences between groups (GAD-7<10 and GAD-7≥10) were assessed using Fisher’s exact and Wilcoxson rank sum tests, for categorical and continuous variables, respectively. Thematic analysis was employed to analyze an open-ended question that asked about the most pressing cause(s) of concern. Results: Of 167 PLHIV contacted, median age was 44 years (IQR:40 – 50), 60% (n=100) were cisgender women and 81% (n=135) had a monthly family income<200 USD. Thirty-eight percent (n=64) had prior history of tuberculosis and 27% (n=45) were living with another comorbidity. A fourth (25%, n=41) had GAD-7 scores indicative of generalized anxiety. PLHIV who had fewer remaining doses of ART had significantly higher GAD-7 scores compared to those that had more doses (p=0.05). Thematic analysis indicated that concerns were both health related and unrelated, and stated temporally. Present concerns were often also projected as future concerns. Conclusions: In a group of socioeconomically disadvantaged PLHIV, a fourth were found to have anxiety, that appeared to be influenced by concerns about ART availability. Furthermore, the persistence of sources of anxiety and therefore an increase in anxiety for these PLHIV is anticipated as the pandemic worsens in India. We recommend the regular utilization of short screening tools for anxiety to monitor and triage PLHIV as an extension of current HIV-services.
Loneliness in early psychosis: A qualitative study exploring the views of mental health practitioners in early intervention services
Authors: Stefanidou Theodora , Wang Jingyi , Morant Nicola , Lloyd-Evans Brynmor , Johnson Sonia
Published: August 2020

Background: Loneliness is an important public health problem with established adverse effects on physical and mental health. Although, people with psychosis often experience high levels of loneliness, relatively little is known about the relationship between loneliness and early psychosis. Potential interventions to address loneliness might be easier to implement early in the illness when social networks and social skills may be more intact than at a later stage. We investigated the views of mental health practitioners about the context and causes of loneliness in people with early psychosis, and about potential interventions.Methods: Semi-structured face-to-face interviews were conducted with mental health practitioners (n=20). Participants were purposively recruited from four early intervention services for first-episode psychosis in the UK. Interviews were transcribed verbatim and thematic analysis was conducted.Results: Participants believed that the majority of service users with early psychosis experience feelings of loneliness. They often saw socially isolated and disconnected clients and believed them to be lonely, but rarely discussed loneliness explicitly in clinical interactions. A combination of symptoms, stigma and negative sense of self were believed to underpin loneliness. Participants could not identify any specific current interventions delivered by their services for tackling loneliness, but thought some routinely provided interventions, including social groups and psychological treatments, could be helpful. They favoured making a wider range of loneliness interventions available and believed that community agencies beyond mental health services should be involved to make these effective and feasible to deliver. They suggested social participation interventions without an explicit mental health focus as potentially promising and valued a co-produced approach to intervention development. Conclusions: This study suggests that loneliness is not routinely discussed in early intervention services, and a targeted strategy for tackling it is lacking. Co-produced, individualised community approaches, and interventions that target symptoms, stigma and negative self-schemas might be beneficial in alleviating loneliness for people with early psychosis. Empirical research is needed to develop and test such interventions.
The Effect of Inhaling Mother’s Breast Milk Odor on the Behavioral Responses to Pain Caused by Hepatitis B Vaccine in Preterm Infants: A Randomized Clinical Trial
Authors: Amiri Adeleh Saebi , aziznejadroshan parvin , Rad Zahra Akbarian , ahangar Hemmat gholinia , Valizadehchari Zahra
Published: August 2020

Background: Pain control in preterm infants is especially important if the necessary measures are not taken in this regard, the evolutionary process of the brain will be disrupted, and the unrelieved pain can have lifelong consequences. The aim of this study was to compare the effect of maternal breast milk odor (MBMO) with that of another mother’s breast milk odor (BMO) on the behavioral responses to pain caused by hepatitis B vaccine (HBV) injection in preterm infants.Methods: This single-blind randomized clinical trial was performed in the neonatal intensive care unit of Babol Rouhani Hospital, Iran from February 2019 to March 2020. Totally, 90 preterm infants who were to receive the HBV for the first time were randomly selected by random sampling. The neonates were randomly assigned into three groups of (A) MBMO (B) another mother’s BMO and (C) control (distilled water).The data were collected using a questionnaire of demographic characteristics and premature infant pain profile (PIPP). Physiological data were recorded by the pulse oximeter immediately before and after the intervention. The data were analyzed using SPSS18 through chi-square, ANOVA and ANCOVA, and P<0.05 was considered as significant level.Results: Before intervention, there was no significant difference between groups in the mean of heart rate, blood pressure and arterial oxygen saturation (SaO2) percentage (P>0.05). After intervention, there was no significant difference between these A, B and C groups in the mean of systolic blood pressure (70.90±8.29, 70.27±6.70 and 71.77±9.07), diastolic blood pressure (43.63±9.59, 41.77±7.10 and 44.03±10.76) and SaO2 percentage (95.20±5.20, 94.00±6.23 and 91.13±11.78), respectively (P>0.05). However, after intervention, there was a significant difference between groups of A, B and C in the mean of heart rate (146. 6±14.3, 153.70±17.5 and 155.70±17.7), respectively (P=0.01). Moreover, the mean PIPP score was 6.6±1.3, 10 ±2 and 11.4±1.9 in groups A, B and C respectively, so that a significant statistical difference was found between groups (P<0.001). Conclusions: Stimulation with MBMO is effective in reducing the pain of preterm infants, so it can be used in less invasive procedures such as vaccination.Trial registration: IRCT, IRCT20190220042771N1. Registered 18 May 2019- Retrospectively registered, https://en.irct.ir/trial/37646
The Effects of Hedgehog Ligand Neutralising Antibody 5E1 in a Mouse Model of Endometriosis
Authors: Cousins Fiona Lyndsay , Farley Johanna K , Kerrigan Rebecca , Mukherjee Shayanti , Darzi Saeedeh , Gargett Caroline E , Deane James A
Published: August 2020

Objective: Endometriosis is a common and painful condition characterized by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. Results: Treatment with 5E1, reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis in the lesions.
Genetic Diversity of Methicillin-Resistant Staphylococcus Aureus Among Japanese Inpatients in the Early 1980s
Authors: Zuo Hui , Uehara Yuki , Lu Yujie , Sasaki Takashi , Hiramatsu Keiichi
Published: August 2020

Background: Methicillin-resistant Staphylococcus aureus (MRSA) was recognized as a serious nosocomial pathogen in Japan starting in the early 1980s. Limited genotypic characteristics on healthcare-associated MRSA (HA-MRSA) associated with “hospital MRSA panics” in Japan in this era. Therefore, this study aimed to determine the characteristics of Japanese HA-MRSA strains in the early 1980s and their linkage with current MRSA strains.Methods: For 194 S. aureus strains isolated in the early 1980s, we determined methicillin resistance phenotypically and genotypically and performed multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, and whole-genome sequencing. Results: Twenty mecA-positive MRSA (10.3%), 8 mecA-negative MRSA (4.1%) and 3 mecA-positive methicillin-susceptible S. aureus (MSSA) (1.5%) strains were identified. The frequent sequence type (ST) was ST30 (n=11), followed by ST5 (n=8), ST81 (n=4), and ST247 (n=3). Rates of SCCmec types I, II, and IV were 65.2%, 13.0%, and 17.4%, respectively. ST30-SCCmec I (n=7) and ST5-SCCmec I (n=5) were predominant genotypes. Only two strains exhibited tst-positive ST5-SCCmec II, which is the current Japanese HA-MRSA genotype. Moreover, 73.3% of SCCmec type I strains were susceptible to imipenem compared with SCCmec type II strains (0%). All ST30 strains shared a common ancestor with strain 55/2053, which resulted in a global pandemic of Panto-Valentine leukocidin (PVL)-positive and penicillin-resistant MSSA spread in Europe and the United States in the 1950s. Conclusions: Our results demonstrated the heterogeneous population structure of Japanese HA-MRSA during the early 1980s, which comprised diverse clones that are mostly rare in recent years. The shift to the current homogenous population structure of HA-MRSA strains consisting of tst-positive ST5-SCCmec II might result from the clinical introduction of new antimicrobials including imipenem.
How Fear and Collectivism Influence Public's Preventive Intention Towards COVID-19 Infection: A Study Based on Big Data from the Social Media
Authors: Huang Feng , Ding Huimin , Liu Zeyu , Wu Peijing , Li Ang , Zhu Tingshao
Published: August 2020

Background
Despite worldwide calls for precautionary measures to combat COVID-19, the public’s preventive intention still varies significantly among different regions. Exploring the influencing factors of the public’s preventive intention is very important to curtail the spread of COVID-19. Previous studies have found that fear can effectively improve the public’s preventive intention, but they ignore the impact of differences in cultural values. The present study examines the combined effect of fear and collectivism on public’s preventive intention towards COVID-19 through the analysis of social media big data.
Methods
The Sina microblog posts of 108,914 active users from Chinese mainland 31 provinces were downloaded. The data was retrieved from 11 January 2020 to 21 February 2020. Afterwards, we conducted a province-level analysis on the contents of downloaded posts. Three lexicons were applied to automatically recognise the scores of fear, collectivism and preventive intention of 31 provinces. Thereafter, a multiple regression model were established to examine the combined effect of fear and collectivism on public’s preventive intention towards COVID-19. The simple slope test and the Johnson-Neyman technique were used to test the interaction of fear and collectivism on preventive intention.
Results
The study reveals that: (a) both fear and collectivism can positively predict people’s preventive intention (fear: β = 0.324, t = 11.685, p < 0.001; collectivism: β = 0.284, t = 10.433, p < 0.001) and (b) there is an interaction of fear and collectivism on people’s preventive intention (β = −0.134, t = − 5.963, p < 0.001), where fear and collectivism reduce each other’s positive influence on people’s preventive intention.
Conclusion
The promotion of fear on people’s preventive intention may be limited and conditional, and values of collectivism can well compensate for the promotion of fear on preventive intention. These results provide scientific inspiration on how to effectively enhance the public’s preventive intention towards COVID-19. For example, ‘Keeping social distance can protect you and your family from infection’ may be a more effective communication strategy than ‘Keeping social distance can protect you from infection’.
Immune-related Gene Data-based Molecular Subtyping Related to the Prognosis for Breast Cancer Patients
Authors: Mu Guoyu , Ji Hong , He Hui , Wang Hongjiang
Published: August 2020

Background Breast cancer (BC), the most frequently seen malignant tumor in female, is associated with increasing morbidity and mortality year by year. Generally, the available treatments for BC include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. Typically, as molecular biology, immunology and pharmacogenomics develop, a growing amount of evidence has suggested that immunocyte infiltration into tumor microenvironment, together with the immunophenotype of tumor cells, would remarkably influence the development and malignant transformation of tumor; as a result, immunotherapy has become a promising therapy for treating BC, which would also affect patient prognosis.Methods In this study, samples collected from TCGA and ImmPort database would be analyzed to search for specific immune-related genes affecting BC patient prognosis. A total of 64 immune-related genes with significant correlation with patient prognosis had been screened and performed shrinkage estimate, among which, 29 most representative ones with significant correlation with patient prognosis had been selected and utilized to establish the prognosis prediction model for BC patients (as referred to as the RiskScore equation). Thereafter, samples in both training set and test set would be substituted into the model, respectively; meanwhile, BC patients would also be divided based on the median RiskScore to assess the efficiency, accuracy and stability of the model in predicting and classifying patient prognosis. Subsequently, functional annotations, GO and KEGG signaling pathway enrichment analysis would be carried out among the 29 as-screened immune-related genes.Results The results found that, these 29 genes could be mainly enriched to numerous BC- and immune microenvironment-related pathways. Eventually, the relationship between RiskScore and the sample clinical features as well as the signaling pathways would be analyzed.Conclusions Our findings indicate that, the prognosis prediction model RiskScore established on the basis of the expression profiles of 29 immune-related genes has displayed high prediction accuracy and stability in identifying the immune features, which can guide the clinicians to diagnose and predict the prognosis for different immunophenotypes, in the meantime of offering numerous therapeutic targets for precisely treating BC in clinic using the identified subtype-specific immune molecules.
Prevalence of Nocturia Among Community-dwelling Adults: A Population-based Study in Malaysia
Authors: Yow Hui-Yin , Tiong John Jeh Lung , Mai Chun-Wai , Werf Esther van der , Zainud Zulkifli Md , Toh Charng-Chee , Ngoo Kay-Seong , Goh Eng-Hong , Fadzli Ahmad Nazran , Lok Sze-Han , Ong Teng Aik
Published: August 2020

Background: Nocturia is widely prevalent condition with detrimental effects on quality of life and general health. In Malaysia, there is a lack of up-to-date prevalence study on nocturia. This study aimed to investigate the prevalence of nocturia and awareness pertaining to nocturia among Malaysian adults.Methods: A cross-sectional population-based study was conducted among Malaysian adults aged ≥ 18 years old. The data was collected by mixed mode self-administered questionnaire from May 2019 to September 2019. Nocturia was defined as one or more voids at night.Results: There were a total of 4616 respondents with 74.5% of response rate. The overall prevalence of nocturia among Malaysian adults was found to be 57.3%. In multivariate analysis, respondents aged 31 – 40 (1.91 [1.52 - 2.40]) or > 60 years old (2.03 [1.48 - 2.71]), and those who presented with hypertension (2.84 [2.28 - 3.53]), diabetes mellitus (1.78 [1.42 - 2.25]), renal disease (3.58 [1.93 - 6.63]) or overactive bladder (1.61 [1.10 - 2.35]) were associated with higher prevalence of nocturia. A significantly lower disease prevalence (p < 0.05) was noted among those aged 41 – 50 (0.73 [0.59 - 0.91]), male (0.78 [0.69 - 0.88]) and Chinese (0.47 [0.30 - 0.74]) or Indian (0.34 [0.21 - 0.54]) ethnicities. A total of 37.3% of respondents with nocturia reported that they faced sleeping difficulty about half the time or more after waking up in the middle of night. Those who had ≥ 2 voids per night experienced significantly higher mean bother score than those who had 1 void per night (p < 0.001). Approximately half (56.7%) of all respondents were not aware that night time urination is a medical condition. Only 25.2% of respondents with nocturia had sought medical attention for their nocturia.Conclusion: The prevalence of nocturia among Malaysian adults is high and strongly influenced by age, gender, race and comorbidities. However, the general awareness on nocturia among Malaysians is poor and relates to low treatment-seeking behaviour we found. The findings also highlighted the impact of nocturia on sleep and the need for nocturia education to better address this disease.
High dose everolimus promotes a pro-inflammatory phenotype and facilitates the epithelial to mesenchymal transition of primary bronchial epithelial cells isolated from cystic fibrosis patients.
Authors: Granata Simona , Santoro Gloria , Masola Valentina , Pontrelli Paola , Sallustio Fabio , Lombardi Gianmarco , Verlato Alberto , Zaza Gianluigi
Published: August 2020

Background: Lung transplantation is still the best therapeutic option for cystic fibrosis (CF) patients, but, unfortunately, immunosuppressive therapies, often employed at high dosages to avoid acute rejection, may induce severe complications. In particular, patients treated with high dose of mammalian target of rapamycin inhibitors (mTOR-Is) may experience lung fibrosis (including bronchiolitis obliterans-organizing pneumonia). Although epithelial to mesenchymal transition (EMT) of airway cells has a central role in this process, the complete biological machinery is not completely clarified.Methods: In order to improve our knowledge on this process, primary bronchial epithelial cells carrying F508del mutation were treated with 5 and 100 nM everolimus (EVE) for 24 hours. Subsequently, RNA was hybridized to the Human HT-12 v3 Expression BeadChip (Illumina). Real-Time PCR was, then, used to validate microarray results and to measure major EMT biomarkers. Trans-epithelial resistance was measured by Millicell-ERS ohmmeter.Results: High dosage EVE induced a significant up-regulation of 42 genes and a down-regulation of 12 genes. After pathway analysis by Gene Set Enrichment Analysis and Ingenuity Pathway Analysis, we found that most of them were implicated in the pro-inflammatory pathway. Real-Time PCR validated these results and revealed that, in addition to pro-inflammatory genes (IL-1α, IL-8, Pim-1 Oncogene), EVE at high dosage was able to up-regulate major EMT biomarkers (such as: alpha-smooth muscle actin, connective tissue growth factor and metalloproteinase 12). In lung, EMT is the convergence point between inflammation and the progression of fibrotic damage. Additionally, EVE at this dosage reduced the trans-epithelial resistance (altering tight junction strength). In contrast, lower EVE did not trigger similar effects.Conclusions: We demonstrated that high dose EVE may trigger a pro-inflammatory/fibrotic biological machinery in bronchial epithelial cells from CF patients. Our results, although obtained in vitro, suggest that solid organ transplant recipients affected by CF should be treated with the lowest possible dose of mTOR inhibitors to minimize/avoid the onset and development of lung complications. In vivo studies might be useful to confirm our hypothesis.
Assessment of the validity of parameters describing temporal and spatial characteristics of spontaneous infant activity in the period of fidgety movements
Authors: Doroniewicz Iwona , Ledwoń Daniel , Bugdol Monika , Kieszczyńska Katarzyna , Affanasowicz Alicja , Matyja Małgorzata , Michnik Robert , Mitas Andrzej W. , Myśliwiec Andrzej
Published: August 2020

Background: The assessment of spontaneous activity of infants is of fundamental importance to the diagnosis and prediction of abnormal psychomotor development in children. Comprehensive and early diagnosis allows for quick and effective treatment and therapy. Subjective methods are based on the knowledge and experience of the diagnostician. The lack of objective methods to assess the motor development of infants makes it necessary to search for solutions for reliable, credible, and reproducible assessment expressed in numerical or pictorial terms. This study discusses the possibilities of pictorial standardization and optimization of measurable infant behavior based on video recordings. Methods: The authors attempt to perform computer analysis of spontaneous movements depending on the left, right, and front head position. The study was based on data of 26 healthy infants aged 7 to 15 weeks, with three infants included in an in-depth analysis. The selected films represented the input data for the parameters used as the author's temporal and spatial characteristics describing the global movements of the upper and lower limbs. The obtained videos were used as the input data for the algorithm of automatic detection of characteristic points using the OpenPose library. Results: The following movement characteristics were analysed: Factor of Movement's Area (FMA) ("amount of movement in the movement"), Factor of Movement's Shape (FMS) ("circularity” or "ellipticity" of the movement), Center of Movement's Area (CMA) ("inward and outward" and "up and down" movements). Preliminary analysis of the videos showed that the activity of the limbs, especially the upper limbs, may depend on the position of the head.Conclusions: The movement behavior of the infants varies in terms of the range and quality of movement, depending on age and head position.
Development and Launch of the First Obstetrics and Gynaecology Master of Medicine Residency Training Programme in Botswana
Authors: Luckett Rebecca , Nassali Mercy , Melese Tadele , Moreri-Ntshabele Badani , Moloi Thabo , Hofmeyr Justus , Chobanga Kudrra , Masunge Japhter , Makhema Joe , Pollard Maisie , Ricciotti Hope , Ramogola-Masire Doreeen , Bazzett-Matabele Lisa
Published: August 2020

Background: Sub-Saharan Africa (SSA) faces a severe shortage of Obstetrician Gynaecologists (OBGYNs). While the Lancet Commission for Global Surgery recommends 20 OBGYNs per 100,000 population, Botswana has only 40 OBGYNs for a population of 2.3 million. We describe the development of the first OBGYN Master of Medicine (MMed) training programme in Botswana to address this human resource shortage.Methods: We developed a curriculum for a 4-year OBGYN MMed at the University of Botswana (UB). We benchmarked curriculum content, learning outcomes, competencies, assessment strategies and research requirements with regional and international programmes. We engaged relevant local stakeholders and developed international collaborations to support in-country subspecialty training. Results: The OBGYN MMed curriculum was completed and approved by all relevant UB bodies within ten months during which time additional staff were recruited and programme financing was assured. The programme was advertised immediately; 26 candidates applied for four positions, and all selected candidates accepted. The programme was launched in January 2020 with government salary support of all residents. The national accreditation process was initiated.Conclusion: Training OBGYNs in-country has many benefits to health systems in SSA. Curricula can be adjusted to local resource context yet achieve international standards through thoughtful design and purposeful collaborations.
The Fluid Management and Hemodynamic Characteristics of PiCCO Employed on Young Children with Severe Hand, Foot, and Mouth Disease—A Retrospective Study
Authors: Wang Feng-yun , Qiang Xin-hua , Jiang Su-hua , Shao Jing-song , Fang Bin , Zhou Lixin
Published: August 2020

Background Hand, foot, and mouth disease (HFMD) is an acute infectious disease caused by human enterovirus 71 (EV71), coxsackievirus, or echovirus, which are particularly common in preschool children. Severe HFMD is prone to pulmonary edema, and successively progresses to respiratory and circulatory failure; thus hemodynamic monitoring and fluid management are important in the treatment process. Methods We reviewed young patients with severe HFMD, caused by EV71, and who had been successfully treated in our department. A total of 20 patients met the inclusion criteria. Some cases were monitored by the pulse indicator continuous cardiac output (PiCCO) technique, and fluid management was administered according to its parameters. With regard to the treatment with PiCCO monitoring, patients were divided into two groups: the PiCCO group and the control group. The groups were then compared comprehensively to evaluate whether PiCCO monitoring could improve the clinical outcomes. Results After analysis, the findings were that although PiCCO failed to shorten the length of ICU stay, reduce the days of vasoactive drug usage, or reduce the number of cases which needed mechanical ventilation, it did reduce the incidence of fluid overload and shortened the days of mechanical ventilation. After effective treatment, PiCCO monitoring showed that the cardiac index (CI) increased gradually(p<0.0001), whereas the pulse (P, p<0.0001), the extra vascular lung water index (EVLWI, p<0.0001), the global end diastolic volume index (GEDVI, p=0.0043), and the systemic vascular resistance index (SVRI, p<0.0001) all decreased gradually. ConclusionOur study discovered that PiCCO hemodynamic monitoring in young children with severe HFMD has potential clinical benefits which can reduce fluid overload(p=0.085) and duration of mechanical ventilation(p=0.028). However, whether it can ameliorate the severity of the disease, reduce mortality, or prevent multiple organ dysfunction remain to be further investigated.
The Development of a Surgical Readiness Interview Tool for Patients to Improve Conversation on Modifiable Risk Factors Prior to Total Joint Arthroplasty
Authors: Barton Kristen I , Hewison Christopher E , Kania-Richmond Ania
Published: August 2020

Background: Total joint arthroplasty (TJA) surgery is conducted forsevere hip and knee osteoarthritis (OA). However, a significant numberof patients referred to orthopedic surgeons with hip and knee OA are not appropriate surgical candidates.Further, many are sent back to their primary care physician because they had not yet exhausted non-surgical options, which suggests the importance surgeons place on exhausting conservative management before proceeding with TJA.The objective of this qualitative inquiry was to 1) explore patients’ perspectives of a surgical readiness interview tool and its potential utility in the management process for patients with OA, and 2) gain input from study participants to further refine the tool and ensure that it is reflective of the patients’ needs and perspectives. Methods: We used a diverse convenience sampling strategy to recruit TJA patients from the hip and knee arthroplasty clinics in Calgary, Alberta. Semi-structured qualitative interviews were conducted using a cognitive interviewing approach in order to elicit information regarding clarity and relevance of the interview tool. All interviews were digitally recorded and transcribed verbatim. Through an iterative process, a coding framework was developed and then applied in the analysis of all interviews. Results: Nine interviews were conducted (n=3 males and n=6), all of whom had a TJA within the previous 12 months. Participants found the questions in the interview tool to be clear and relevant, and nothing listed was unexpected. All participants expressed that they felt comfortable discussing the content of the interview tool with their doctors. The main themes that emerged from the interviews include 1) the need for clarifications, 2) patient-oriented changes, and 3) expectation management. While gaining insight from study participants, the qualitative inquiry confirmed utility of the tool improve the conversation about surgical readiness and utilizing conservative management prior to TJA. Conclusions: Overall, participants were positive about the interview tool and felt that it would lead to better care provision. We recommend the use of the interview tool in primary care settings to support the conversation on modifiable risk factors and non-surgical management strategies for OA prior to TJA.
Impact of Urgent and Emergency Care Vanguards on Delayed Transfers of Care in England
Authors: Malisauskaite Gintare , Jones Karen , Allan Stephen , Roland Daniel , Birks Yvonne , Baxter Kate , Gridley Kate
Published: August 2020

Objectives: To assess the relationship between Urgent and Emergency Care (UEC) Vanguards, which include as an aim the integration of healthcare and social care sectors, and Delayed Transfers of Care (DTOC) at Local Authority level in England. Methods: Difference-in-difference and fixed effects panel estimations were used to compare DTOC between UEC partner site Local Authorities with non-UEC Local Authorities employing quarterly data on days of DTOC from Local Authorities in England for the period 2010 to 2017. Robustness checks included employing Ordinary Least Squared (OLS) and synthetic control estimations; differences between the UEC and non-UEC sites were checked prior to the start of the Vanguards. Results: A statistically significant negative relationship was found between UEC Vanguards and DTOC rates that is robust to various specification checks with no indication of UEC participant sites having lower DTOC rates prior to the start of the initiative. Conclusions: UEC Vanguards appear to be associated with 40.5% lower DTOC rates at 1% significance level compared with other English Local Authorities. The empirical evidence indicates a statistically significant impact; however, more research is required to explain the reasons for this relationship.
Diagnostic Accuracy of Plasma Ghrelin Concentrations in Pediatric Sepsis -associated ARDS: A Single-center Cohort Study
Authors: yuan xiu , Li Shaojun , Zhou Liang , LI yanru , tang tian , Cheng Yuwei , Ao Xiaoxiao , Tan Liping
Published: August 2020

Background: Ghrelin is the endogenous ligand of growth hormone secretagogue receptor 1a (GHSR1a), which can regulate immunity and inflammation. To assess the diagnostic value of plasma ghrelin levels in sepsis-associated pediatric acute respiratory distress syndrome (PARDS).Methods: We recruited patients from the PICU of a third-class teaching hospital who met the diagnostic criteria for sepsis from January 2019 to January 2020. Clinical data, laboratory indicators, plasma ghrelin concentrations, and inflammatory factors of cohort were evaluated in detail, and patients were followed up for 28 days. The area under the receiver-operating characteristic curves (AUROC) was calculated using logistic regression to calculate and positivity cut-offs was tested. Ghrelin's ability to diagnose and differentiate sepsis-associated PARDS were determined. The log-rank test was used to compare the survival curves of different ghrelin level groups.Main results: Sixty-six PICU patients (30 with ARDS, 36 without ARDS) who met the diagnostic criteria of sepsis were recruited. The ghrelin level was significantly higher in the sepsis patients of the ARDS group than in those of the non-ARDS group. The AUROC of ghrelin was 0.708 (95% confidence interval: 0.584–0.833) and the positivity cutoff value was 445 pg/mL. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (–LR) of plasma ghrelin for diagnosis of sepsis with PARDS were 86.7%, 50.0%, 59.1%, 81.8%,1.734, and 0.266, respectively. The survival rate of sepsis patients was significantly improved when the ghrelin level was >445 pg/mL.Conclusions: Ghrelin plasma was higher in sepsis-associated PARDS, and accompanied by the increase of inflammatory factors. The increased plasma ghrelin may be due to the anti-inflammatory response, which may be a protective factor in children with sepsis. Yet, there is no evidence to prove that elevated ghrelin appears to be a promising diagnostic indicator of sepsis-associated PARDS. In addition, the ghrelin levels may be a positive predictor of sepsis.Trial registration: Clinicaltrials, ChiCTR1900023254. Registered 1 December 2018 - Retrospectively registered, http://www.clinicaltrials. gov/ChiCTR1900023254.
WITHDRAWN: Ribosomal Protein S27-Like is overexpressed in glioma cells and inhibition of RPS27L expression suspends the tumorigenesis
Authors: Sun Zhongzheng , Xue Hao , Wei Yan , Wang Shaobo , Xu Jianye , Qian Mingyu , Wang Chaochao , Zhao Rongrong , Wang Chengwei , Li Gang
Published: August 2020

Background: Ribosomal Protein S27-Like is an evolutionarily conserved ribosomal protein and the role of RPS27L influencing the malignance of several cancers has been reported. However, its effects on glioma were still unknown. This investigation aims to characterize the clinical significance and the biological functions of RPS27L in gliomas.Methods: TCGA databases were explored to analyze the correlation between RPS27L expression and the clinical characteristics of glioma patients. Immunohistochemical staining was performed on glioma cases and normal brain tissues. The function of RPS27L in glioma was further explored using U87MG and A172 cell lines and a orthotopic xenograft model of nude mice.Results: Data obtained from TCGA database showed higher expression of RPS27L in glioma than normal, and the overall survival was lower in the high expression group. Immunohistochemistry showed the expression levels of RPS27L were increased with the tumor grade rising in gliomas. Functional assays showed knockdown of RPS27L inhibited proliferation, cell cycle transition, migration and invasion, while promoted apoptosis. Data of western blot indicated that knockdown of RPS27L increased the level of p21，Bax and Cleaved Caspase-3 while decreased the level of CDK4, cyclinD1, cyclinE1, Bcl-2 and MMP2, MMP9 in glioma cells. In vivo, the growth of orthotopic glioma xenografts was suppressed by expression of RPS27L shRNA, and the tumors with RPS27L shRNA showed less aggressiveness and reduced expression of Ki67, Bcl-2 and MMP2. Conclusions: RPS27L is overexpressed in glioma cells. Knockdown of RPS27L could inhibit the proliferation, migration and invasion while promote apoptosis of glioma cells in vitro and in vivo. RPS27L might be a potential prognostic biomarker and possible target for future therapy in glioma.
Immune‐related Long Noncoding RNA Signature for Patients with Cervical Cancer
Authors: Zheng Jianfeng , Tong Jinyi , Cao Benben , Zhang Xia , Niu Zheng
Published: August 2020

Background: Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune‐related lncRNAs(IRLs) of CC has never been reported. This study aimed to establish an IRL signature for patients with CC.Methods: The RNA-seq dataset was obtained from the TCGA, GEO, and GTEx database. The immune scores（IS）based on single-sample gene set enrichment analysis (ssGSEA) were calculated to identify the IRLs, which were then analyzed using univariate Cox regression analysis to identify significant prognostic IRLs. A risk score model was established to divide patients into low-risk and high-risk groups based on the median risk score of these IRLs. This was then validated by splitting TCGA dataset(n=304) into a training-set(n=152) and a valid-set(n=152). The fraction of 22 immune cell subpopulations was evaluated in each sample to identify the differences between low-risk and high-risk groups. Additionally, a ceRNA network associated with the IRLs was constructed.Results: A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson’s correlation analysis between immune score and lncRNA expression (P < 0.01). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values (P < 0.05) were identified which demonstrated an ability to stratify patients into low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low‐risk group showed longer overall survival (OS) than those in the high‐risk group in the training-set, valid-set, and total-set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four IRLs signature in predicting the one-, two-, and three-year survival rates were larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Conclusions: Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four-IRLs in the development of CC were ascertained preliminarily.