bluuebunny/crossref_metadata_2025 huggingface dataset:
Arthroscopic Anterior Talofibular Ligament Repair with Use of a 2-Portal Technique
Authors: Shimozono Yoshiharu , Hoberman Alexander , Kennedy John G. , Takao Masato
Published: December 2019

Ankle sprains are common musculoskeletal injuries, with approximately 27,000 occurring every day in the U.S. alone. The anterior talofibular ligament (ATFL) is the most commonly injured ligament. Although most acute lateral ankle sprains can be treated conservatively, up to 20% of these injuries result in chronic lateral ankle instability and may require surgical stabilization. Recently, an arthroscopic lateral ankle ligament repair technique has become increasingly popular. This minimally invasive procedure is expected to reduce postoperative pain and promote faster recovery. The current article presents an ATFL repair using a 2-portal, non-distraction arthroscopic technique. Chronic lateral ankle instability refractory to physical therapy for 3 to 6 months is the main indication for surgical treatment, and sufficient quality of ligament tissue remnant is required for arthroscopic repair. Compared with an open procedure, equivalent clinical results and earlier recovery following arthroscopic ATFL repair have been reported. The major steps of the procedure, demonstrated in this video article, are (1) placement of portals for the arthroscopic procedure, (2) suture anchor insertion into the distal aspect of the fibula, (3) needle insertion into the ATFL remnant, (4) a lasso-loop stitch using a suture relay technique, (5) reattachment of the ATFL remnant, and (6) postoperative protocol. Complications are rare, and earlier return to daily activities compared with a standard open technique can be achieved.
Feasibility of home-based HIV counselling and testing and linking to HIV services among women delivering at home in Geita, Tanzania: A household longitudinal survey
Authors: Adinan Juma , Adamou Bridgit , Amour Caroline , Shayo Aisa , Kidayi Paulo Lino , Msuya Levina
Published: December 2019

Background Substantial number of women who deliver at home (WDH) are not captured in prevention of mother-to-child transmission (PMTCT) services. This delays HIV infection detection that negatively impacts endeavours to fight the HIV pandemic and the health of mothers and children. The study objective was to determine the feasibility of home-based HIV testing and linking to care for HIV services among WDH in Geita District Council, Tanzania.Methods A longitudinal household survey was conducted. The study involved all mentally-able women who delivered within two years (WDTY) preceding the survey and their children under the age of two. The study was conducted in Geita District Council in Geita Region, Tanzania from June to July 2017. Geita is among the region with high HIV prevalence and proportion of women delivering at home.Results Of the 993 women who participated in the study, 981 (98.8%) accepted household-based HIV counselling and testing (HBHCT) from the research team. HIV prevalence was 5.3% (52 women). HBHCT identified 26 (2.7%) new HIV infections; 23 (23.4%) were those tested negative at ANC and the remaining three (0.3%) were those who had no HIV test during the ANC visit. Among the 51 HIV+ women, 21 (40.4%) were enrolled in PMTCT services. Of the 32 HIV+ participants who delivered at home, eight (25.8%) were enrolled in the PMTCT compared to 100 percent (13/13) of the women who delivered at a health facility.Conclusion HBHCT uptake was high. HBHCT detected new HIV infection among WDH as well as seroconversion among women with previously negative HIV tests. The study findings emphasize the importance of extending re-testing to women who breastfeed. HBHCT is feasible and can be used to improve PMTCT services among WDH.
An emotion regulation training in the treatment of obesity in young adolescents: The protocol of a Randomized Controlled Trial
Authors: Debeuf Taaike , Verbeken Sandra , Boelens Elisa , Volkaert Brenda , Malderen Eva Van , Michels Nathalie , Braet Caroline
Published: December 2019

Background:
The prevalence rates of childhood obesity are increasing. The current multidisciplinary treatments for (childhood) obesity are effective, but only short term and rather moderately. A possible mechanism to explain the onset and maintenance of childhood obesity is a maladaptive way of regulating high levels of stress and emotions. Therefore, the current RCT-study aims to test the effectiveness of adding an emotion regulation training to care as usual (multidisciplinary obesity treatment) in young inpatients (10-14) involved in an obesity treatment program compared to care as usual alone.
The research model for this RCT-study states that when high levels of stress are regulated in a maladaptive way, this can contribute to the development of obesity.
Method: The current study will recruit 140 youngsters (10-14 years) that are involved in an inpatient multidisciplinary obesity treatment (MOT) program. After giving consent to participate in the study, youngsters will be randomly assigned, during consecutive waves, to one of two conditions: care as usual (receiving MOT) or intervention (receiving MOT and on top an emotion regulation training). The training itself consists of 12 weekly sessions, followed by a booster session after three and five months. The participants will be tested pre, post and at 6 months’ follow-up. We hypothesize that, compared to the control condition, youngsters in the intervention condition will (1) use more adaptive emotion regulation strategies and (2) report less emotional eating, both primary outcome measures. Moreover, on the level of secondary outcome measures, we hypothesize that youngsters in the intervention condition, compared with the control condition, will (3) report a better sleep quality, (4) undergo an improved weight-loss and weight-loss maintenance and (5) experience a better long-term (6-months) psychological well-being.
Discussion: This study will add to both the scientific and clinical literature on the role of emotion regulation in the development and maintenance of different psychopathologies, as emotion regulation is a transdiagnostic factor.
Trial Registration: The RCT-study protocol is registered at ISRCTN Registry, with study ID ‘ISRCTN 83822934’. Registered at 13 December 2017; http://www.isrctn.com/ISRCTN83822934
Haploidentical Related Donor versus Matched Sibling Donor Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome Aged Over 50 Years: A Single-Center Retrospective Study.
Authors: Huang Jiafu , Huang Fen , Fan Zhiping , Xu Na , Xuan Li , Liu Hui , Shi Pengcheng , Jiang Ling , Zhang Yu , Sun Jing , Liu Qifa
Published: December 2019

BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Increasing data supports the utility of haploidentical related donor (HID) HSCT in fit older patients and resulting in improvement of outcomes. This study compared the outcomes of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients age ≥50 years underwent haploidentical related donor (HID) or matched sibling donor (MSD) allogeneic hematopoietic stem cell transplantation (allo-HSCT).METHODS We retrospectively studied 38 patients with AML/MDS aged ≥50 years who underwent HID transplantation and compared their outcomes with 55 similarly aged patients who underwent MSD transplantation.RESULTS The 100-day cumulative incidence of II-IV° acute graft-versus-host disease (GVHD) were 34.2 ± 7.7% and 23.6 ± 5.7%, respectively, in HID and MSD groups (P = 0.189), and III-IV° acute GVHD were similar between two groups (5.3% and 7.3%, respectively, P=0.700). The 2-year cumulative incidence of limited and extensive chronic GVHD was not statistically different in HID and MSD groups(22.8 ± 10.8% vs. 18.2 ± 6.0% and 18.3 ± 10.4% vs. 22.1 ± 6.8%, P = 0.890 and P=0.424, respectively). The 2-year cumulative incidences of relapse (29.5±10.3% and 20.7 ±6.1%, P=0.458), 2-year overall survival (58.5±9.7% and 67.9±6.8%, P=0.373), 2-year transplant-related mortality (17.3±6.4% and 15.0±5.3%, P=0.717), 2-year progression free survival (56.8±9.7% and 64.6±7.4%, P=0.312) were similar in the two groups.CONCLUSION The present data showed similar outcomes in patients aged 50 years and older underwent HID compared to MSD at our institution.
The Influence of dietary diversity on the nutritional status of children between 6 and 23 months of age in Tanzania
Authors: Khamis Ahmed Gharib , Mwanri Akwilina Wendelin , Ntwenya Julius Edward , Kreppel Katharina
Published: December 2019

Background:Undernutrition poses a serious health challenge in developing countries and Tanzania has the highest undernutrition burden of Eastern and Southern Africa. Poor infant and young child feeding practices have been identified as the main causes for undernutrition. Here we examined to what extent dietary diversity is associated with undernutrition among children of 6 to 23 months in Tanzania. Methods: Using existing data from the Tanzania Demographic and Health Survey of 2015-2016, we carried out secondary data analysis. Stunting, wasting and underweight were calculated based on 2006 WHO standards. A composite dietary diversity score was created by summing the number of food groups eaten the previous day as reported for each child by the mother ranging from 0 to 7. Then, minimum dietary diversity (MDD) of 4 food groups out of seven was used to assess the diversity of the diet given to children. Bivariate and multivariate logistic regression techniques were used to assess the crude and adjusted odds ratios of stunting, wasting and being underweight. Results: A total of 2,960 children were enrolled in this study. The majority (74%) of children did not reach the MDD. The most commonly consumed types of foods were grains, roots and tubers (91%), and Vitamin A containing fruits and vegetables (65%). Consumption of a diverse diet was significantly associated with a reduction of stunting, wasting and being underweight in children. The likelihood of being stunted, wasted and underweight was found to decrease as the number of food groups consumed increased. Children who did not receive the MDD had a significantly higher likelihood of being stunted (AOR=1.37, 95% CI; 1.13-1.65) and underweight (AOR=1.49, 95% CI; 1.15-1.92), but this was not the case for wasting. Consumption of animal-source foods has been found to be associated with reduced stunting among children. Conclusion: Consumption of a diverse diet is associated with a reduction in undernutrition among children of 6 to 23 months in Tanzania. Measures to improve the type of complementary foods in order to meet the energy and nutritional demands of children should be considered in Tanzania.
Immunogold labeling of synaptic vesicle proteins in developing hippocampal neurons
Authors: Tao-Cheng Jung-Hwa
Published: December 2019

Synaptic vesicles (SV) contain high concentrations of specific proteins. How these proteins are transported from soma to synapses, and how they become concentrated at SV clusters at presynaptic terminals were examined by immunogold electron microscopy in dissociated rat hippocampal neurons at 3-6 days in culture, a developmental stage when axonal transport of SV proteins is robust. In neuronal somas, labels for the SV integral membrane proteins (synaptophysin, SV2, VAMP/synaptobrevin, and synaptotagmin) were localized at Golgi complexes and other membranous structures that were dispersed in the cytoplasm as individual vesicle/vacuoles. These vesicles/vacuoles became aggregated in axons, with the size of aggregates ranging from 0.2 to 2 µm in length. Pleomorphic vesicle/vacuoles within the aggregate were typically larger (50-300 nm) than SVs, which were uniform in size at ~40 nm. These pleomorphic vesicles/vacuoles are likely transport cargos carrying SV integral membrane proteins from the soma, and sorted into axons at early developmental stages. Serial thin sections of young axons indicated that many labeled aggregates were not synaptic, and in fact, some of these axons were without dendritic contacts. In contrast, labels for two SV associated proteins, synapsin I and a-synuclein, were not localized at the Golgi complexes or associated with membranous structures in the soma, but were dispersed in the cytoplasm. However, these SV-associated proteins became highly concentrated on clusters of SV-like vesicles in axons, and such clusters were already distinctive in axons as early as 3 days in culture. These clusters consisted of ~4 - 30 vesicles in single thin sections, and the vesicles were of a uniform size (~40 nm). Serial sectioning analysis showed that these clusters could be part of nascent synapses or exist in axons without any dendritic contact. Importantly, the vesicles were intensely labeled for SV integral membrane proteins as well as SV-associated proteins. Thus, these EM observations reveal that the two groups of proteins, SV integral membrane and SV-associated, proceed through different routes of biosynthesis and axon transport, and are only sorted into the same final compartment, SV clusters, when they are in the axons.
Effect of a Pedometer-based Walking Intervention on Body Composition in Patients with ESRD: A Randomized Controlled Trial
Authors: Sheshadri Anoop , Kittiskulnam Piyawan , Lai Jennifer C. , Johansen Kirsten L.
Published: December 2019

Background: A randomized trial of a pedometer-based intervention with weekly activity goals led to a modest increase in step count among dialysis patients. In a secondary analysis, we investigated the effect of this intervention on body composition.Methods: 60 dialysis patients were randomized to standard care or a 6-month program consisting of 3 months of pedometers and weekly step count targets and 3 months of post-intervention follow-up. We obtained bioelectrical impedance spectroscopy (BIS) data on 54 of these patients (28 control, 26 intervention) and used linear mixed-modeling (adjusted for sex and dialysis modality) to estimate differences in change in total-body muscle mass (TBMM) adjusted for height2, fat mass (kg), and body mass index (BMI) (kg/m2) between control and intervention groups.Results: The median age of participants was 57.5 years (53 – 66), and 76% were men. At baseline, there was no significant difference between groups in age, BMI, race, or body composition, but there were more men in the intervention group. After 3 months, patients in the intervention group increased their average daily steps by 2,414 (95% CI 1047, 3782) more than controls (p<0.001), but there were no significant differences in body composition. However, at 6 months, participants in the intervention had a significantly greater increase from baseline in TBMM of 0.7 kg/m2 (95% CI 0.3, 1.13), decrease in fat mass (‑4.3 kg [95% CI ‑7.1, ‑1.5]) and decrease in BMI (-1.0 kg/m2 [95% CI -1.8, -0.2]) relative to controls. In post-hoc analysis, each increase of 1,000 steps from 0 to 3 months was associated with a 0.3 kg decrease in fat mass (95% CI 0.05, 0.5) from 0 to 6 months, but there was no dose-response relationship with TBMM/ht2 or BMI.Conclusion: A pedometer-based intervention resulted in greater decreases in fat mass with relative preservation of muscle mass, leading to a greater decrease in BMI over time compared with patients not in the intervention. These differences were driven as much by worsening in the control group as by improvement in the intervention group. Step counts had a dose-response relationship with decrease in fat mass.Trial Registration: ClinicalTrials.gov (NCT02623348). 02 December 2015. https://clinicaltrials.gov/ct2/show/NCT02623348
MicroRNA-20a mediates the cytotoxicity of natural killer cells in endometriosis via ERG/HLX/STAT4/perforin axis
Authors: Chen Li-Juan , Hu Bin , Han Zhi-Qiang , Ni Jian , Zhou Yong-Ming , Chen Xue-Xing , Zhou Hao
Published: December 2019

The authors have withdrawn this preprint from Research Square
Neuro-medical complications of fluoride toxicity among populations living in fluorosis endemic region of the Ethiopian Rift Valley
Authors: Ayele Biniyam Alemayehu , Yifru Yared Mamushet , Tekle-Haimanot Redda , Godebo Tewodros Rango
Published: December 2019

Background Fluorosis is endemic in many countries of Asia, South America, and Africa. In Africa, the countries located across the Great East African Rift Valley, including Ethiopia are a hotspot for fluorosis. While excessive and chronic exposure to fluoride causes dental and skeletal fluorosis, emerging studies have shown its adverse health effects in cognition, memory, learning and the function of central nervous system. The aim of this study is to assess neurological features of populations chronically exposed to a wide range of fluoride concentrations in drinking water wells in the Ethiopian Rift Valley.Method We conducted a study on 318 individuals living in rural villages located in fluoride endemic areas of the Ethiopian Rift Valley. Drinking water samples were collected from 23 community well sites, and analyzed for fluoride concentrations. Detailed clinical evaluations of skeletal fluorosis, neurologic history, and physical examination were performed in the study participants. Association between different fluoride concentrations and clinical features of fluorosis were done using chi square and crude odds ratio (OR).Results The mean age of the study participants was 28.0±14.9 years. Male accounted 55.7% of the subjects participated. About 80% of the participants were from the communities who used water from wells containing fluoride concentration >2 mg/L. The mean fluoride concentration in drinking water samples was 6.8±4.3 mg/L (range: 0.3 to 15.5 mg/L). Among the neurologic complications, headache, fatigue, and paresthesia accounted for 67%, 56.3%, and 37.5%, respectively. Impaired lumbar mobility, impaired squatting, impaired neck mobility, and knocked knee occurred in 22.3%, 6.6%, 2.2%, and 1.6%, respectively. Impaired lumbar mobility and kyphosis showed statistically significant association with higher fluoride concentration in drinking water (>2 mg/L) (P <0.05), while impaired squatting did not (p = 0.9) as compared to baseline fluoride concentration < 2mg/L.Conclusion Our findings strongly suggest that the adverse neurological and medical effects associated with prolonged exposure to elevated concentrations of fluoride in drinking water. We recommend conducting large scale epidemiological study in fluoride endemic areas using controlled population to better understand non-skeletal fluorosis related to neurological and medical complications.
Strengthening the quality of paediatric primary care: A process evaluation of a complex health systems intervention in South Africa
Authors: Curran Robyn Leigh , Murdoch Jamie , Cornick Ruth Vania , Picken Sandra , Bachmann Max , Bateman Eric , Simelane Makhosazana Lungile , Fairall Lara Rosemary
Published: December 2019

BACKGROUND: Innovative strategies like WHO’s Integrated Management of Childhood Illness (IMCI) have resulted in progress in addressing infant and child mortality. However, the needs of children continue to present a burden upon primary healthcare services. The capacity of services and quality of care offered require greater support to address these needs and extend integrated curative and preventive care, specifically, for the well child, the child with a long-term health condition and the child older than 5 years, not included in IMCI. In response to these needs, the PACK Child intervention was developed, based on a similar successful approach in adults, that expands the scope and reach of integrated management and training programmes for paediatric primary care. We report findings from the process evaluation of the integration of PACK Child intervention within the existing primary health care system. METHODS: A mixed methods process evaluation was completed in ten primary health care facilities in the Western Cape province in South Africa, where clinicians were trained to integrate PACK Child into routine practice. Qualitative data included transcribed interviews with managers, clinicians, caregivers and policymakers; audio-recordings and observational fieldnotes of training, consultations and clinic flow. Quantitative data were collected from training logs, questionnaires, and consultations. Qualitative data were analysed using linguistic ethnographic techniques, including conversation and thematic analysis. Quantitative data were analysed descriptively. RESULTS: Influence of PACK Child on clinical practice: Longer consultations, improved clinical knowledge and practice, better teamwork, strengthening of appropriate referrals and inclusion of psychosocial risk screening. Implementation fidelity of PACK Child was hindered by over-reliance on documentation and embedded checklist approach to consultations limited to acute episodic illnesses. PACK Child increased caregiver participation during consultations. CONCLUSIONS: The PACK Child intervention has strengthened primary care for children despite institutionalised care provided by a limited number of clinicians focusing on acute illness with little participation of the caregiver. With refinement of the programme, there is potential for PACK Child to strengthen paediatric care in low-resource settings.
Kefir Ameliorates Specific Physiological and Behavioural Impairments in a Mouse Model of Autism Spectrum Disorder
Authors: Wouw Marcel van de , Vig Giulia MD , Lyte Joshua M , Boehme Marcus , Gual Andreu , Walsh Aaron M , Clarke Gerard , Cotter Paul D. , Dinan Timothy G. , Cryan John F.
Published: December 2019

Autism spectrum disorders (ASD) is one of the most severe developmental disorders, affecting on average 1 in 150 children worldwide. There are limited treatment options for ASD symptoms and there is therefore a great need for more effective strategies to improve quality of life in ASD subjects. The gut microbiome has recently emerged as a therapeutic target in ASD. A novel modulator of the gut microbiome, the traditionally fermented milk drink kefir, has recently been shown to modulate the microbiota and decrease repetitive behaviour, one of the hallmarks of ASD. As such, we hypothesised that kefir could ameliorate the behavioural phenotype of ASD in the animal model of ASD; the BTBR T + Itpr3 tf /J mouse strain. Adult mice were administered either kefir (UK4) or milk control for 3 weeks as treatment lead-in, after which they were assessed for their behavioural phenotype using a battery of tests. In addition, we assessed systemic immunity by flow cytometry. We found that kefir decreased repetitive behaviour. Furthermore, kefir prolonged stress-induced increases in corticosterone 60 minutes post-stress, which was accompanied by an ameliorated innate immune response as measured by LY6C hi monocyte levels. Furthermore, kefir increased the levels of anti-inflammatory Treg cells in mesenteric lymph nodes. Altogether, our data show that kefir modulates peripheral immunity in an anti-inflammatory manner and can ameliorate specific ASD behavioural dysfunctions, indicating that kefir supplementation might prove a viable strategy in improving quality of life in ASD subjects.
Involvement of neutrophils in machineries underlying the rupture of intracranial aneurysms
Authors: Kushamae Mika , Miyata Haruka , Shirai Manabu , Shimizu Kampei , Oka Mieko , Koseki Hirokazu , Abekura Yu , Ono Isao , Nozaki Kazuhiko , Mizutani Tohru , Aoki Tomohiro
Published: December 2019

Background: Subarachnoid hemorrhage due to rupture of an intracranial aneurysm (IA) has quite a poor prognosis once after the onset despite of the modern technical advancement. The development of a novel therapeutic modality to prevent rupture or a diagnostic method to stratify dangerous lesions from many stable ones is thus mandatory for social health. To this end, mechanisms underlying rupture of lesions should be clarified. Methods: We and others have developed the rat model in which induced IAs spontaneously rupture resulting in subarachnoid hemorrhage. To clarify molecular cascades regulating rupture, we obtained gene expression profile data from rupture-prone lesions and revealed the enrichment of neutrophil-related terms in rupture-prone lesions by Gene Ontology analysis. Next, to validate a role of neutrophils in rupture of lesions, G-CSF was administered to a rat model. Results: As a result, G-CSF treatment not only increased number of neutrophils infiltrating in lesions but also significantly facilitated rupture of the lesions without increase the incidence. To clarify mechanisms how neutrophils facilitate rupture of IAs, we used HL-60 cell line and found that inflammatory stimuli enhanced the collagenolytic activity of MMP9. Immunohistochemical study using IA lesions from a rat model identified neutrophils as a major type of cells producing MMP9 around a site of rupture and consistently the collagenolytic activity of MMP9 was detected in ruptured lesions. Conclusions: These results combined together suggest the crucial role of neutrophil to rupture of IAs and also propose the potential of this type of cells as a candidate of therapeutic or diagnostic targets.
Effects of the grade/price of and thickness of cigarette on the PM2.5 concentration of smoke
Authors: Ji Shengzhe , Liu Zhen , Sha Yuxue , Wang Yiwen , Wang Qaing , Liu Peng
Published: December 2019

Background: Due to lower tar and nicotine, high grade/price and slim cigarette are believed as “safe cigarette” and cause less tobacco smoke pollution (TSP) advocated by cigarette producers. However, cigarette smokes comprise thousands of harmful constituents, only two substances cannot represent TSP. Then in this study, we wanted to discover if the grade/price and thickness of cigarette affect TSP.Methods: Slim (S) and regular (R) cigarette with different grades/prices were selected to investigate TSP via measurement PM2.5 in a closed chamber (1 m3). Sidestream smoke was collected through cigarette combustion. Mainstream smoke was collected using piston-operated smoking machine. Results: In sidestream smoke, cigarette grade/price did not affect PM2.5 of R or S cigarette. But in mainstream smoke, grade/price acted discrepancy roles in different thickness cigarette. In R cigarette, PM2.5 of lowest grade/price (R5) was lowest. While in S cigarette, PM2.5 of lowest grade/price (S5) was highest. Cigarette thickness obviously affected PM2.5. PM2.5 of R cigarette was 116% higher than S cigarette in sidestream. In mainstream smoke, magnification was down to 31%, despite PM2.5 of R cigarette was also higher.Conclusions: Irrespective of sidestream or mainstream smoke, the grade/price of cigarette did not obviously affect PM2.5. But which was significantly influenced by cigarette thickness. Although S cigarette PM2.5 was significantly lower than R cigarette, it cannot mean that S cigarette was less harmful. Because harmfulness of smoke was not only affected by cigarette but also by smoker inhale habits. It needs further experiments to evaluate the harmfulness of slim cigarette.
Disease progression modelling from preclinical Alzheimer’s disease (AD) to AD dementia
Authors: Cho Soo Hyun , Woo Sookyoung , Kim Changsoo , Kim Hee Jin , Jang Hyemin , Kim Byeong C. , Kim Si Eun , Kim Seung Joo , Kim Jun Pyo , Jung Young Hee , Lockhart Samuel , Ossenkoppele Rik , Landau Susan , Na Duk L. , Weiner Michael , Kim Seonwoo , Seo Sang Won
Published: December 2019

Background: To characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. Methods: We used longitudinal data from 127 participants with preclinical AD and 309 participants with mild cognitive impairments (MCI) due to AD from the Alzheimer’s Disease Neuroimaging Initiative. In order to develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale–Cognitive Subscale 13 (ADAS-cog 13) scores according to the follow-up time for each cohort, determined the time point at which the estimated scores of ADAS-cog 13 for the two cohorts first overlapped, and shifted the ADAS-cog 13 scores for the latter cohort at this time point to connect the two cohorts and to combine the data into a single unified progression course. Results: The estimated years for progression from the median ADAS-cog 13 score in the preclinical AD cohort (9.3 points) to the median ADAS-cog 13 score at the time of progression in the participants who progressed from preclinical AD to MCI due to AD (16.0 points) was 7.8 years. The estimated years for progression from preclinical AD to the median ADAS-cog 13 score at the time of progression in those who progressed from MCI to due AD to AD dementia (26.8 points) was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in female APOE ε4 carriers and most slowly in male APOE ε4 non-carriers ( p < 0.001). Conclusion: Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.
A genetic variant in the promoter of lncRNA MALAT1 is related to susceptibility of ischemic stroke
Authors: wang yan , Gu Xi-Xi , Huang Hua-Tuo , Liu Chun-Hong , Wei Gui-Jiang , Wei Ye-Sheng
Published: December 2019

Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was aberrantly expressed in diverse diseases including ischemic stroke (IS). This study aimed to investigate the association between MALAT1 polymorphism and IS risk. We performed the genotyping of rs600231, rs1194338, rs4102217 and rs591291 in the promoter of MALAT1 by SNPscan method. Quantitative PCR was used to determine the levels of MALAT1 relative expression. We found the rs1194338 C>A variant in MALAT1 promoter was associated with IS risk (AC vs. CC: adjusted OR = 0.623, 95% CI, 0.417-0.932, P = 0.021; AA vs. CC: adjusted OR = 0.474, 95% CI, 0.226-0.991, P = 0.047; AC/AA vs. CC: adjusted OR = 0.596, 95% CI, 0.406-0.874, P = 0.008; A vs. C adjusted OR = 0.658, 95% CI, 0.487-0.890, P = 0.007). The IS patients showed higher expression levels of MALAT1 compared with the control group ( P < 0.05), but patients with AC/AA genotypes of rs1194338 have no significant difference compared to CC genotype ( P > 0.05). In addition, no significant differences were observed in blood lipid levels among SNPs of MALAT1 ( P > 0.05). These results suggest that the rs1194338 AC/AA genotypes may be a protective factor for IS, which mechanism needs to be further explored.
A novel Tweak/ Stat1/ Snhg3 positive feedback circuit contributes to the glial cell activation in temporal lobe epilepsy mice
Authors: Chen Li , Shi Rui , Zhang Xin , Hou Chen , Zhang Xiaohui , Chong Li , Yuan Rui , Li Rui
Published: December 2019

Gliosis is an important feature of temporal lobe epilepsy (TLE), but the regulatory mechanism of glial cell activation remains unclear. Small nucleolar RNA host gene 3 (Snhg3) has been reported to be involved in cell proliferation and migration in various cancers. However, its role in the development of TLE has been hardly explored. Here, we established a mouse TLE model by injecting intraperitoneally with pilocarpine, and found that Tweak expression was significantly induced in TLE mice. Inhibiting Tweak expression by the injection of siRNA notably rescued the glial cell activation, neuroinflammatory cytokine secretion and cognitive behavior disorder in TLE mice. Molecular mechanism studies showed that cell proliferation, migration, inflammatory factor secretion, Stat1 pathway activation and Snhg3 expression were promoted after we incubated Tweak recombinant protein (rTweak) with mouse astrocytes (MAs). The Tweak neutralizing antibody (anti-Tweak) showed the opposite effect to that of rTweak. In subsequent researches, we found that Stat1 directly bound to Snhg3 promoter and they elevated the expression of each other. Moreover, both of them boosted cell proliferation, migration, inflammatory factor secretion and Tweak expression. Thus, we found a feedback regulation loop consisting of Tweak/Fn14, Stat1/ p-Stat1 and Snhg3 in the MAs, which increased cell activation. In vivo experiment demonstrated that the reduction of Snhg3 inhibited glial cell activation induced by TLE, and Tweak/Stat1/Snhg3 feedback circuit also existed in TLE mice. In short, our research testified a feedback regulation loop consisting of Tweak/Stat1/Snhg3, which was involved in the activation of hippocampal glial cells in TLE mice.
Dysfunctional cerebrovascular tone contributes to cognitive impairment in a non-obese rat model of prediabetic challenge: Role of suppression of autophagy and modulation by anti-diabetic drugs
Authors: Fakih Walaa Kamel , Mroueh Ali , Salah Houssein F. , Eid Ali , Obeid Makram F. , Kobeissy Firas F. , Darwish Hala , El-Yazbi Ahmed F.
Published: December 2019

Early stages of metabolic dysfunction, including prediabetes, pose a high risk for cardiovascular and cognitive impairment. While several pathological mechanisms linked advanced manifestations of metabolic deterioration, such as hypoglycemia, to neuronal inflammation and cognitive decline, little is known about the detrimental processes in effect at the early stages. To address this gap, we used a non-obese rat model of prediabetes developed in our laboratory. After 12 weeks of mild hypercaloric feeding, these rats developed hyperinsulinemia and increased fat/lean ratio without an increase in blood glucose level or body weight. These rats showed vascular dysfunction manifested as exaggerated contractility as a consequence of perivascular adipose inflammation. In this study, the mild metabolic challenge was associated with impaired hippocampal-dependent cognitive functions, spatial learning and memory and spontaneous object recognition. In line with our previous findings in this model, prediabetic rats had an augmented cerebrovascular myogenic tone demonstrated as an increased pressure-evoked contraction in pressure myography experiments on rat middle cerebral artery segments. The presumed brain hypoperfusion was accompanied by increased expression of hypoxia-inducible factor-1a in the hippocampus, together with markers of mitochondrial dysfunction and increased oxidative stress. In parallel, increased p62 expression and LC3 puncta in the prediabetic rat hippocampus, as well as increased Akt and mammalian target of rapamycin phosphorylation indicated a possible repression of autophagic flux. Consequently, the examination of the hippocampal CA1 area revealed increased CD68 and IBA-1 staining consistent with microglial activation and neuroinflammation, in addition to increased TUNEL staining and caspase-3 activity indicative of elevated neuronal apoptosis. Interestingly, a two-week treatment with non-hypoglycemic doses of metformin or pioglitazone, previously shown to improve adipose inflammation and vascular function, reversed the cerebrovascular and molecular alterations in the hippocampus. This was associated with an amelioration of cognitive function. The results of the present study indicate that early metabolic challenge leads to cerebrovascular alteration potentially leading to hippocampal hypoxia and mitochondrial dysfunction. Together with suppression of autophagy, these effects culminate in hippocampal inflammation and apoptosis possibly underlying the cognitive impairment.
Screening hypoxia-related genes as prognostic biomarkers and modeling the individualized prognostic predictor in hepatocellular carcinoma
Authors: Guo Hao , Zhang Jun Yan , Lv Shu Jing , Wang Zhi , Zhang Wei Wei , Liu Kun Li , Cheng Yan , Zhou Jing
Published: December 2019

Background Hypoxia closely relates to malignant progression and appears to be prognostic for outcome in hepatocellular carcinoma (HCC). Our research aims to mine the Hypoxic related genes (HRGs) on the role of clinical prognosis in HCC. Moreover, we construct and define a model of prognostic predictor (PP) to estimate and improve prognosis of HCC patients.Results 37 differentially expressed HRGs were obtained. It contained 28 up-regulated and 9 down-regulated genes. After the univariate Cox regression model analysis, we obtained 27 prognosis-related HRGs. Of these, 25 genes were risk factors for cancer and 2 genes were protective factors. The PP was composed of the 10 key genes (HDLBP, SAP30, PFKP, DPYSL4, SLC2A1, PGK1, ERO1A, LDHA, ENO2, TPI1), and significantly divided patients of HCC into high- and low-risk groups according to overall survival (OS) ( P <0.001). We got the Area Under Curve(AUC) value of risk score calculated by PP was 0.777, which much bigger than other clinical parameters. Besides, PP was verified as an independent prognosis-related parameter (in univariate analyse, HR=1.484, 95% CI=1.342–1.642, P<0.001; in multivariate analyse, HR=1.414, 95% CI=1.258–1.588, P <0.001). Finally, the application of PP in clinic was concluded that the higher the patient's risk score, the higher the corresponding tumor stage and T stage, and the patient's prognosis was poor.Conclusions This study provides hypoxic related molecular targets for the therapeutic intervention. In addition, an individualized prognostic predictor was constructed to predict prognosis for HCC patients .
Delayed Laser photocoagulation following intravitreal anti–vascular endothelial growth factor injection allows immature retinal vessels to regrow without recurrence of retinopathy of prematurity
Authors: Nam Ki Yup , Lee Ji Eun , Lee Joo Eun , Kim Hyun Wong , Lee Sang Joon
Published: December 2019

Purpose: The effects of delayed laser photocoagulation (LP) for ROP patients who received intravitreal anti–vascular endothelial growth factor injections (IVAs) on peripheral vascularization and disease recurrence in ROP patients. Methods: A total of 26 consecutive infant eyes of 14 patients who received IVA treatments were retrospectively investigated. The patients were divided into two groups depending on the initial treatment as follows: IVA group and prompt LP group. Recurrence of ROP, growth of the retinal vessels, and associated complications were evaluated. Results: There were 16 eyes in the IVA group and 10 eyes in the LP group. In the IVA group, delayed LP was performed in six eyes due to recurrences of ROP. In 16 eyes of the IVA group, the retinal vessels grew upto Zone III in eyes received IVA only. Among the IVA groups, Delayed LP was needed in six eyes due to ROP recurrence following IVA. Delayed LP was performed average 7~8 weeks after IVA, which could give the immature neurovascular tissues time to continue vascular development upto Zone II without further ROP recurrence. However, the prompt LP group did not show vessel development beyond the laser scar. Conclusions: Delayed LP following IVA might provide a chance for retinal vessel development in the immature retina to continue without unexpected ROP recurrences.
Exploring the risk of Middle East Respiratory Syndrome- coronavirus among expatriate healthcare workers. A comparative epidemiological study of Saudi Arabian and South Korean healthcare workers
Authors: Qureshi Mohammed Owais , Chughtai Abrar , Seale Holly
Published: December 2019

Background In comparison to South Korea, which was able to contain the outbreak of Middle East respiratory syndrome corona virus (MERS-CoV) in 2015, new cases are still emerging in the Kingdom of Saudi Arabia. The Saudi Arabian healthcare sector, which is dependent on the expatriate workforce to cater to its growing local healthcare demands, has been reporting multiple healthcare-associated MERS-CoV outbreaks since 2012. In this paper, we compare the epidemiology of MERS-CoV among healthcare workers (HCWs) in Saudi Arabia and South Korea and to ascertain the risks of MERS-CoV among expatriate HCWs. Methods Data were collected from publicly available resources such as World Health Organization and health department websites. A line list of all reported cases of MERS-CoV among HCWs in Saudi Arabia and South Korea was prepared and analysed. Results Among the total infected HCWs in Saudi Arabia, 84.6% (n=192/227) were expatriates. The mean age of infected HCWs in both settings was similar (Saudi Arabia 38 years, South Korea 39 years). Female HCWs were more likely to be infected, while male HCWs were more likely to die. In Saudi Arabia, 36.5% (n= 68/186) of HCWs with MERS-CoV were asymptomatic, compared to 7% (n=2/28) HCWs in South Korea. Most of the expatriate HCWs in Saudi Arabia were asymptomatic (78%, n=53/68) to MERS-CoV. Unlike South Korea, in Saudi Arabia, a diversity of HCWs other than doctors, and nurses were also infected with MERS-CoV. Conclusions A high proportion of expatriate HCWs were infected with MERS-CoV in Saudi Arabia which highlights the need for adequate training and education in this group about emerging infectious diseases and the appropriate strategies to prevent acquisition. Also, we did not find any policy statements restricting the contact of HCWs, vulnerable to MERS-CoV like pregnant HCW, HCWs over the age 60, HCWs with underlying comorbidity etc, from getting in proximity with a suspected or potential MERS-CoV infected patient. Policy development in this regard should be a priority, to contain healthcare-associated transmission of emerging and remerging infectious diseases like MERS-CoV. Further studies should be conducted to determine social, cultural and other factors contributing to high infection rate among expatriate HCWs.
The efficacy of two different doses of hepatitis B immunoglobulin in interrupting mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis
Authors: Fu Shan , Yao NaiJuan , Feng YaLi , Li Juan , Wu YuChao , Tian Zhen , Yang Yuan , Yan TaoTao , Chen Yaolong , Zhao Yingren , Chen Tianyan , Liu Jinfeng
Published: December 2019

Background: There isn’t consensus about the optimal dose of hepatitis B immunoglobulin (HBIG) in combination with hepatitis B vaccine to preventing mother-to-child transmission (MTCT) of hepatitis B virus(HBV).Methods: We systematically searched MEDLINE, Embase, and Cochrane Library from database inception to Jan 16, 2019 for studies. The primary outcome was HBsAg and/or HBV DNA positive in infants at 6-12 months old. We performed a meta-analysis with a random-effects model to calculate a pooled estimate of MTCT.Results: We included 31 studies, comprising of 12151 infants. There wasn't significant differences in the pooled MTCT rates between 100 IU HBIG group and 200 IU HBIG group (5% vs 5%, P = 0.757). When further stratified according to HBeAg status, in HBeAg(+) mothers, 7% (95%CI 4%-11%) infants became chronic HBV infection in 100 IU HBIG group compared to 7% (95%CI 5%-9%）in 200 IU group. The rates were 1% (95%CI 0%-2%) in 100IU group and 0% (95%CI 0%-1%) in 200IU group in infants born to HBeAg(-) mothers, respectively. When further comparing MTCT in infants from mothers with HBV DNA≥1×10^6 IU/mL, the pooled MTCT rate was 12% (95%CI 7%-17%) in 100IU group and 8% (95%CI 5%-13%) in 200IU group, respectively. In addition, comparative analysis of four studies concerning two different dosages of HBIG further manifested the comparability.Conclusion: 100 IU HBIG is sufficient in preventing MTCT for infants from chronic hepatitis B infected mothers, regardless of maternal HBeAg status or viral load.
Further report on the higher frequency of withdrawal as contraception among Iranian women: demand for more powerful education programs in health care systems
Authors: Karami Fatemeh , Gholami Fatemeh , Ghasemi Asemeh
Published: December 2019

Background: Family planning has critical role in improvement of various aspects of community health. Owing to the limited and incomplete previously performed studies, the present work was conducted to determine the frequency of contraception methods and most important factors in selection of them among women of Tehran province.Methods: The present assay was designed as analytical and observational cross-sectional study. A questionnaire including 24 questions was filled for 395 women (18-40 years old) refereed to multiple private clinics in three selected strict of Tehran. Questions were designed in order to address the type of contraception method besides multiple social, economic and cultural factors which may affect the selection and demographic characteristics of enrolled samples.Results: The frequency of the type of contraceptive methods was significantly different among women in different age categories (p-value=0.01). Overall rate of using contraceptive methods was 75.2% while remaining of the participants believed in no need for contraception. The most prevalent contraceptive methods were traditional methods (55.9%), modern methods (29.1%), combination of methods (8.1%) and surgery methods (6.8%), respectively. Status of housing was the only factor among economic issues which was meaningfully associated with the selection of the method. Conclusion: High prevalence of natural contraceptive methods even among highly educated women is relying on the demand for more education regarding the selection of best methods based on the background information, obstetrics history, age and economic status of women. Results of the present study can be implicated in further health programs to improve family planning.
Frequency and predictors of the Lupus Low Disease Activity State in Chinese patients with systemic lupus erythematosus: a prospective observational cohort study
Authors: Gao Dai , Hao Yanjie , Mu Lin , Xie Wenhui , Fan Yong , Ji Lanlan , Zhang Zhuoli
Published: December 2019

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant risk of organ damage. Lupus Low Disease Activity State (LLDAS) was generated as a potential treatment target for SLE. Previous studies had validated that the maintenance of LLDAS can predict reduced damage accrual or flare. The objective of this study was to estimate the time to LLDAS and the predictors of time to LLDAS in our prospective observational cohort of Chinese patients with SLE. Methods Patients were from Peking University First Hospital SLE cohort and those having not fulfilled LLDAS at enrolment were included in this study. The time to LLDAS and annual cumulative probabilities of LLDAS achievement were estimated by the Kaplan-Meier approach. The predictors of time to LLDAS were identified by univariate and multivariable Cox proportional hazards. Results A total of 574 patients with SLE were included and 435 (75.8%) of them achieved LLDAS during a median 4.2 years of follow-up. The median time to LLDAS was 19.0 months and the cumulative probabilities at 1, 2, 3, 5 and 10 years were 19.8%, 57.6%, 72.0%, 85.1% and 98.0%, respectively. In multivariable Cox models, older age at disease onset, treatment-naïve and hydroxychloroquine prescription were found to be independent predictors of shorter time to LLDAS, after adjusted by daily prednisone dose, SLE Disease Activity Index 2000 and physician’s global assessment. Finally, we developed a matrix model based on the identified independent predictors to present the time to LLDAS in patients with respective characteristics. Conclusions Our study proved that LLDAS is attainable as an early treatment target for SLE in Chinese patients. The older age at disease onset, treatment-naïve and hydroxychloroquine prescription were independent predictors of shorter time to LLDAS.