bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic Analysis of the Reproductive Effects on Immunity in the Clam Meretrix Petechialis During the Breeding Season
Authors: Wang Di , Liu Baozhong
Published: September 2020

Background: Immune defense and reproduction are both physiologically demanding processes, therefore the trade-off is expected between them in breeding season. Although this balance strategy has been extensively studied in many species, it is still rarely noticed in mollusc. Moreover, summer mortality of marine bivalve often occurs during breeding season and reproduction is suspected to play a significant role for the mass death. Results: To address if spawning affects immunity to cause clam death, we performed transcriptome and gene expression analyses in the clam Meretrix petechialis pre-/post-spawning. DEGs enrichment analysis revealed important immune signaling pathways and key genes changed after spawning. Further analysis showed females up-regulated genes involved in apoptosis, TLR signal pathway and heat shock, whereas males down-regulated complement-related genes after spawning. Additionally, both genders of clams up-regulated its immune response level to against Vibrio infection after spawning revealed by the changes of four immune-related DEGs. Conclusions: The spawning indeed affected the clam immune resistance. The immune and defense related genes and pathways obtained here provide important insights into the molecular mechanisms of physiological acclimation and immune response under reproduction-influence and offers some clues to explain the possible reason for clam summer mortality.
Subdivision of metastatic colorectal cancer for identifying patients who benefit more from primary tumor resection
Authors: Luo Dakui , Shan Zezhi , Liu Qi , Cai Sanjun , Li Qingguo , Li Xinxiang
Published: September 2020

Background

Stage IV colorectal cancer (CRC) patients are heterogeneous with distinctive clinicopathologic features and prognosis. Radical resection of primary tumor and distant metastases is associated with improved survival outcomes in metastatic CRC. The value of palliative primary tumor resection is controversial. The present study explored which subgroups benefited more from primary tumor resection in metastatic CRC.
Methods

Between 2004 and 2015, patients with metastatic CRC were identified using the surveillance, epidemiology, and end results (SEER) database. Uni- and multivariable Cox regression analysis were performed to identify factors associated with decreased cancer-specific mortality. The subgroups were divided based on the independent prognostic factors.
Results

Age, marital status, race, serum CEA, histologic type, differentiation, tumor location, surgery of primary or metastatic lesion, site of metastases, number of metastatic sites, chemotherapy and radiotherapy were identified as independent prognostic factors. Patients with non-white race, normal serum CEA, non-signet ring cell carcinoma, well or moderate differentiation, surgery of metastases, isolated liver metastasis, single metastasis, receiving chemotherapy or radiotherapy presented more survival benefit from primary tumor resection.
Conclusion

Subgroup of metastatic CRC optimizes decision-making and selected patients will benefit more from primary tumor resection.
Short Reports Low Prevalence of Toxoplasma Gondii DNA in the Fresh Milk of Cattle in China
Authors: Wang Yong-Liang , Meng QingFeng
Published: September 2020

Background: It is generally recognized that there is a risk for humans to acquire toxoplasmosis through consumption of raw milk from infected animals. Although several studies have been conducted to detect the seroprevalence of T. gondii in cattle in China, no study has been conducted to detect T. gondii DNA in milk of cattle in China. Thus, the present study was firstly conducted to explore the prevalence of T. gondii DNA in fresh milk of cattle in China. Results: A total of 2092 blood samples and fresh bovine milk were collected from six provinces between January 2018 and June 2019, respectively, and examined by ELISA and semi-nested PCR, respectively. In total, 123/2092 (5.88%) of the blood samples and 22/2092 (1.05%) of the milk samples were positive for T. gondii, respectively. Fifteen of these 22 positive milk samples (68.18%) were animals who also recorded serologically positive. Moreover, cattle and milk from family farming have significantly higher T. gondii prevalence than those from commercial farm. Conclusions: To our knowledge, this is the first report of T. gondii DNA was found in the fresh milk of cattle in China, suggesting that the consumption of raw milk from seropositive cattle could be a potential source of human infection.
Implementation Research Training for Learners in Low- and Middle-Income Countries: Evaluating Behavior Change after Participating in A Massive Online Open Course
Authors: Launois Pascal , Maher Dermot , Certain Edith , Ross Bella , Penkunas Michael J.
Published: September 2020

Background: Implementation research (IR) can play a critical role in the delivery of disease control interventions, particularly in low- and middle-income countries (LMICs). The growing demand for IR training has led to the development of a range of training programs and university courses, the majority of which can not be accessed by learners in LMICs. This article reports on the evaluation of a massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases hosted by the World Health Organization on the topic of IR with a focus on infectious diseases of poverty. This study followed Kirkpatrick’s Model to evaluate training programs with a specific focus on post-training changes in behavior.Methods: MOOC participants were invited to take part in an anonymous online survey examining their IR knowledge and how they applied it in their professional practice approximately 1-1.5 years after completing the MOOC. The survey contained 43 open-ended, multiple choice and Likert-type questions. Descriptive statistics were calculated for the quantitative data and responses to the open-ended questions were thematically coded.Results: A total of 748 MOOC participants responded to the survey. The demographic profile of the survey respondents aligned with that of the MOOC participants, with nearly 70% of respondents originating from Africa. Responses to the quantitative and open-ended survey questions revealed that respondents’ IR knowledge had improved to a large extent as a result of the MOOC, and that they used the knowledge and skills gained in their professional lives frequently. Respondents most often cited changes in their conceptual understanding of IR and understanding of the research process as substantial areas of change influenced by participating in the MOOC.Conclusions: These findings indicate that the MOOC was successful in targeting learners from LMICs, in strengthening their IR knowledge and in contributing to their ability to apply it in their professional practice. The utility of MOOCs for providing IR training to learners in LMICs, where implementation challenges are encountered often, makes this platform an ideal standalone learning tool or one that could be combined with other training formats.
How can we improve patients’ access to new drugs under uncertainties?: South Korea’s experience with risk sharing arrangements
Authors: Lee Boram , Bae Eun-Young , Bae SeungJin , Choi HyunJin , Son Kyung-Bok , Lee Young-Sil , Jang Suhyun , Lee Tae-Jin
Published: September 2020

Background: New drugs including cancer drugs and orphan drugs are becoming increasingly more expensive. Risk sharing arrangements (RSAs) could manage the risk based on both financial impact and the health outcome of new drugs if reimbursed. To improve patients’ access to new drugs under uncertainties, many developed countries have adopted RSAs. In this study, we aimed to understand the effects of RSAs in South Korea on patients’ access.Methods: We reviewed current status of RSA drugs in South Korea. The number of appraisals and time gap between market approval and reimbursement per RSA drug were considered to quantify improvement of patients’ access as they showed how rapidly decisions on reimbursement of RSA drugs were derived. Then, we applied a comparative analysis to determine whether the RSA drugs in South Korea were reimbursed in the UK, Italy, and Australia. Most data for this study were obtained from websites of the governmental department/agencies responsible for appraisal of drug reimbursement in each country. And literatures related to RSAs were investigated as well.Results: The eligibility for Korean RSAs had two key components - drugs for cancer and rare diseases and not having other alternative treatments. As of the first half of 2019, there were 39 RSA drugs reimbursed in South Korea, the majority of which were financial-based schemes. Refund and expenditure cap were the representative types (89.7%). After introduction of RSAs, the time gap and number of appraisals were decreased. Based on the indications of RSA drugs, the level of drug coverage in South Korea was found lower than Italy, similar to the UK, and higher than Australia.Conclusions: RSAs in South Korea significantly enhanced patients’ access to new drugs and led to the alleviation of patients’ out-of-pocket expenses. The drug coverage of South Korea had a level comparable to that of other countries. This study provides implications for countries that have a dual mission of containing pharmaceutical expenditure and improving access to new drugs.
Differences in Psychological Characteristics Between People With Knee Osteoarthritis From Japan and Australia
Authors: Uritani Daisuke , Campbell Penny K. , Metcalf Ben , Egerton Thorlene
Published: September 2020

BackgroundThe aim of this study was to investigate differences in psychological characteristics between people with knee osteoarthritis (OA) from Japan and Australia.Methods A total of 62 adults from Japan and 168 adults from Australia aged over 50 years with knee pain were included. Japanese data were collected from patients with knee OA diagnosed by medical doctors. Australian data were baseline data from a randomized controlled trial. Psychological characteristics evaluated were depressive symptoms (depression subscale of the 21-item short-form of Depression Anxiety Stress Scale), fear of movement (Brief Fear of Movement Scale for Osteoarthritis), and pain catastrophizing (Pain Catastrophizing Scale). Psychological characteristics were compared between the Japanese and Australian cohorts by calculating 95% confidence intervals (CIs) for difference of the mean. To test for equivalence of the average values of characteristics, the equivalence margin was set at 0.5 standard deviations (SD) of the mean, where these SDs were based on the Australian data. When the 95%CI for the difference of the mean value lay entirely within the range of equivalence margin (i.e. between -0.5 and 0.5 times the Australian SD), the outcome was considered equivalent.ResultsThere were no significant differences between the groups from Japan and Australia for depressive symptoms (mean ± SD; Japan 4.9±5.4, Australia 4.2±4.7) and fear of movement (11.7±3.8, 12.5±3.2, respectively). Mean (95%CI) between group differences were 0.75 (-0.79 to 2.28) for depressive symptoms and -0.77 (-1.77 to 0.22) for fear of movement. Based on the equivalence test, 95%CIs of mean difference between groups for depressive symptoms was within the range of equivalence margin (±2.35). However, the lower limit of the 95% CI of difference in mean for fear of movement (-1.77) was just outside the lower equivalence margin (-1.60). People from Japan with knee OA showed significantly higher pain catastrophizing (20.7±11.0) than those from Australia (14.8±9.6).ConclusionsPeople from Japan with knee OA showed higher pain catastrophizing than people from Australia. The level of depressive symptoms and fear of movement appeared to be equivalent between people from the two countries.
Perspectives on External Support to Low Level Private Health Facilities in Management of Childhood Infections in Mbarara District, Uganda: A Qualitative Study With Health Workers and Policy Makers
Authors: Mwanga-Amumpaire Juliet , Kalyango Joan Nakayaga , Källander Karin , Sundararajan Radhika , Owokuhaisa Judith , Obua Celestino , Alfvén Tobias , Ndeezi Grace
Published: September 2020

Background: With the under-five child mortality rate of 46.4 deaths per 1000 live births, Uganda needs to accelerate measures to reduce child deaths in order to achieve the Sustainable Development Goal 3. While 60-70 % of frontline health services are provided by the private sector, many low level private health facilities are unregistered, unregulated, and often miss out on innovative strategies rolled out by the Ministry of Health. Low level private health facilities need support in order to provide quality health care. We explored the perspectives of health workers and policy makers on external support given to low level private clinics providing health care for children. Methods: In-depth interviews were conducted from May to December 2019 with 43 purposively selected key informants. They included 30 health care professionals treating children in low level private clinics and 13 policy makers from Mbarara district and the Uganda Ministry of Health directly involved with ensuring quality of child health. The issues discussed included their views on the quantity, quality, factors determining support received and preferred modalities of support to low level private health facilities. Using an inductive approach, interview transcripts were coded to identify categories and themes.﻿Results: We identified three themes which emerged from the data 1) External support is needed to address socio-economic, regulatory and knowledge gap issues, 2) Current support is not optimal, and, 3) Ideal support underscores working together. While the Ministry of Health recognises its’ responsibility to provide support and guidance to public and private health facilities, it acknowledges lack of support for low level private health facilities currently. Health providers emphasised technical capacity building and more supportive supervisory visits but not simply policing and apportioning blame.Conclusion: The current support being given to low level private health facilities (LLPHF) is inadequate. The support needs to be tailored to the needs of the facility and health facilities have to proactively ask for support. Capacity building with emphasis on training and supportive supervision are key strategies for providing external support to LLPHF.
Trends of Road Traffic Injury in Ethiopia, 2014 to 2017: eHMI Based Data Analysis.
Authors: Hunduma Fufa , Leulseged Belayneh
Published: September 2020

Background: Road traffic injury (RTI) is one of the leading causes of mortality and morbidity globally. It accounts for more than 1.35 million deaths per year. It has multiple risk factors that contribute to its occurrence. Low and middle-income countries are affected severely, thus, Ethiopia is among the most affected countries. Aim of this assessment is to analyze three years of Electronic Health Management Information System (eHMIS) surveillance data of Road traffic injuries in Ethiopia as general to describe the trends of injury based on sex, age, place, and time. Methods: eHMIS Road Traffic accident data were reviewed retrospectively for three years period (2007 – 2009 Ethiopian calendar (E.C) / 2014 to 2017) and Analysis was done by Microsoft Excel. Result: The trend of injury in Ethiopia increased from 69882 to 100,628 and inpatient death increased from 125 to 265 over the last three years. Males were affected more, hence contributed to 63.64% of total cases. Those who were above 15 years of age contributed to 80.6% of total cases. Cases reached their peak during the dry season of regions. Harari region had the highest incidence of injury; more than 2000 cases per 100,000 over three years period. Conclusion: This analysis revealed that in Ethiopia burden of Road Traffic Injury (RTI) was increasing against the plan of the country. Being male and adult has a greater risk of RTI. Harari region and Dire Dawa has a much higher incidence than the national level. High-level political commitment, immediate decisions, and actions are needed to halt the problem.
Covid-19 in South America: Clinical and Epidemiological Characteristics Among 381 Patients During the Early Phase of the Pandemic in Santiago, Chile
Authors: Rodriguez Macarena , Peters Anne , Perez Inia , Spencer Maria , Barbe Mario , Porte Lorena , Weitzel Thomas , Aylwin Mabel , Vial Pablo , Araos Rafael , Munita Jose M
Published: September 2020

Background: Understanding the characteristics of the Covid-19 pandemic in different geographical regions, ethnic and socioeconomic settings are of emerging importance. This study presents the demographic and clinical features of SARS-CoV-2 infected patients in a large private healthcare center in Santiago, Chile, during the first month of the pandemic.Methods: We analyzed the demographics, laboratory and clinical characteristics including severity and outcome of all patients diagnosed with Covid-19 during the first month of the pandemic. SARS-2-CoV infection was confirmed by RT-PCR in nosopharyngeal samples. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality. Clinical and laboratory parameters of hospitalized patients were analyzed regarding their association with the primary outcome. Results: From March 3 to April 4, 2020, 3679 individuals were tested for SARS-CoV-2 in our hospital. Of those, 381 had Covid-19 and were included into this analysis. Most patients (99.2%) were Chileans, 12% returning from recent travel. The median age was 39 years (IQR 31-49) and 52% were female. A total of 88 patients (23.1%) were hospitalized; 18 (3.7%) required ICU and/or died. The overall mortality was 0.7%. Increased body mass index (BMI) and elevated C-reactive protein (CRP) were independently associated with ICU care or death.Conclusion: During the first weeks of the pandemic in Chile, most Covid-19 patients were young, with low rates of hospitalization, ICU requirement, and fatality. BMI and CRP on admission were predictors for severity. Our data provide important information on the clinical course and outcome of Covid-19 in a Latin American setting.
Impossible to go Beyond Beef? A Nutriomics Comparison
Authors: Vliet Stephan van , Bain James , Muehlbauer Michael , Provenza Frederick , Kronberg Scott , Pieper Carl , Huffman Kim , Kraus William
Published: September 2020

Concerns regarding the effects of red meat on human and environmental health are prompting consumer interest in plant-based diets. As global food systems strive to meet the dietary needs of an estimated mid-century population of 10 billion, a new generation of plant-based meat alternatives—formulated to mimic the taste and nutritional composition of red meat—have attracted considerable consumer interest, research attention, and media coverage. We used untargeted metabolomics to provide an in-depth comparison of the nutrient profiles of grass-fed ground beef and a market-leading plant-based meat alternative. Metabolomics revealed a 90% difference in nutritional profiles beef and a popular plant-based meat, many of which can have important consumer health implications. This information could not be determined from their Nutrition Facts, which suggests nutritional similarity. Our findings indicate that beef and a popular plant-based meat should not be viewed as nutritionally interchangeable, but as complementary in terms of provided nutritional entities. As society aims to increase food production with ~ 60% by 2050, the meat and the plant-based meat industries will likely coexist and have to complement each other in order this reach this goal.
Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test
Authors: Leligdowicz Aleksandra , Conroy Andrea , Hawkes Michael , Richard-Grennblatt Melissa , Zhong Kathleen , Opoka Robert , Namasopo Sophie , Bell David , Liles W , Costa Bruno da , Jüni Peter , Kain Kevin
Published: September 2020

Identifying febrile children at risk of sepsis in low-resource settings can improve survival, but recognition triage tools are lacking. Here we test the hypothesis that measuring circulating markers of immune and endothelial activation may identify children at risk of sepsis due to all causes. In a prospective cohort study of 2,502 children in Uganda, we show that Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) measured at first clinical presentation, had high predictive accuracy for subsequent in-hospital mortality. sTREM-1 had the best performance, versus 10 other markers, with an AUROC for discriminating children at risk of death of 0.893 in derivation (95% CI 0.843-0.944) and 0.901 in external validation (95% CI 0.856-0.947). sTREM-1 cutoffs corresponding to a negative likelihood ratio (LR) of 0.10 and a positive LR of 10 classified children into low (1306 children, 53.1%), intermediate (942, 38.3%) and high (212, 8.6%) risk zones. The estimated incidence of death was 0.3%, 3.6%, and 31.0%, respectively, suggesting sTREM-1 could be used to risk-stratify febrile children. These findings support sTREM-1 as the basis for rapid triage test for all cause fever syndromes in children in low-resource settings.
Distributed Region-Based Monitoring in Low-Power Listening Wireless Sensor Networks
Authors: Pattamasiriwat Krita , Jaikaeo Chaiporn
Published: September 2020

Advancement in IoT technology and the concept of Information-Centric Networking lead to less importance of node individuality since several nodes can work interchangeably. Multiple sensor nodes can be grouped into a region and monitored as one instance to guarantee sufficient coverage over the region. Therefore, a single node fault often does not need to be reported unless it is the last node in the region. In addition, there are occasions where a central monitor station cannot rely on continuous data delivery from nodes or regions to decide whether they are still alive, such as situations when nodes are deployed to detect rare events. Moreover, low-power listening MAC protocols, which significantly help reducing power consumption while nodes are mostly idle, put a lot more work on the transmission process. In such situations it is desirable to minimize status reports to the central monitor station. A distributed region-based monitoring scheme, or DRMON, is then proposed to facilitate this circumstance. This approach designates a representative to each region so that it can be used as an indicator of the region's status with a mechanism to re-elect a new representative until all nodes in the respective region are dead, implying region inactiveness. We evaluate the suitability of DRMON over various scenarios in two aspects: centralized vs. distributed monitoring schemes and individual-based vs. region-based monitoring schemes. Simulation results indicate that region-based schemes outperform the individual schemes in terms of power consumption and scalability when the number of regions is low. The distributed schemes also yield better efficiency in terms of message overhead and load distribution. In addition, detection accuracy of all schemes is not significantly different and fault detection delay is guaranteed. This outcome suggests that in the case where existence of individual node is out of concern, distributed region-based fault monitoring scheme could be employed to reduce energy usage and lower message overhead while retaining the detection accuracy.
Serum sialic acid could be a diagnostic candidate of unstable angina and its expression in different numbers of lesion vessels in acute myocardial infarction: a retrospective study
Authors: Wu Yuling , Pan Nana , Tan Lijuan
Published: September 2020

Background: Acute coronary syndrome is one of the leading causes of morbidity and mortality worldwide. Intracoronary thrombosis caused by atherosclerotic unstable plaque rupture or erosion is considered as main pathological basis. There have no identified biomarkers about diagnosis of unstable angina and prognosis of acute myocardial infarction. Methods: A total of 509 consecutive patients admitted to the Affiliated Hospital of Qingdao University from February 2019 to December 2019 were successively recruited in this retrospective study and divided into three groups, unstable angina, acute myocardial infarction and death occurred within 24 hours of acute myocardial infarction in hospital and then to compare with a total of 87 healthy people (control group) during the same time from Regular Physical Examination Center of the Affiliated Hospital of Qingdao University. Mann-Whitney test, Kruskal-Wallis test, and Chisquared test were used to analyze different types of grouping. Univariate and multivariate regression analyses were performed to analyze the risk factors. Relative operating characteristic (ROC) curve analysis was also performed to determine the power of test. Results: our study suggested that serum sialic acid has a good diagnostic value in patients with unstable angina. Moreover, serum sialic acid is an independent risk factor of acute myocardial infarction. Serum sialic acid could be a candidate to distinguish Single/Double vascular lesions from Triple vascular lesions in acute myocardial infarction. Conclusions: serum sialic acid is a potential biomarker to distinguish unstable angina from normal and estimate the number of diseased vessels in patients with acute myocardial infarction.
Activity of BDNF and MMP-9 in Structural Synaptic Modulation in Patients with Schizophrenia Undergoing Rehabilitation
Authors: Markiewicz Renata , Dobrowolska Beata , Plech Tomasz
Published: September 2020

The aim of the study was to evaluate the levels of brain derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in two groups of schizophrenic patients receiving rehabilitation and to find out whether there existed relationships between the levels of these biomarkers and the severity of psychopathological symptoms, changes in event-related potentials (ERP), and quantitative EEG parameters. The study involved two groups of patients diagnosed with schizophrenia in remission who participated in a 12-week conventional rehabilitation program (Group 1) or Biofeedback training (Group 2). The following parameters were assessed: BDNF levels, MMP-9 levels, ERP, QEEG, and psychopathological symptoms (PANSS). (1) The magnitude of changes in the investigated parameters was similar in both groups. (2) Comparable therapy outcomes were obtained for all the dependent variables except for BDNF, whose levels were higher in the GSR-BF patients. GSR Biofeedback can be used as a new alternative to conventional rehabilitation. BDNF can be used as a target in the evaluation of the effectiveness of various rehabilitation modalities, in contrast to MMP-9, which, despite its role in neuromodulation, cannot be treated as a marker of treatment outcomes.
Alteration of Transthyretin and Thyroxine-Binding Globulin in Major Depressive Disorder: Multiple Reaction Monitoring-Based Proteomic Analysis
Authors: Woo Hye In , Park Jisook , Lim Shinn-Won , Kim Doh Kwan , Lee Soo-Youn
Published: September 2020

Background: Major depressive disorder (MDD), common mental disorder, lacks objective diagnostic and prognosis biomarkers. The objective of this study was to perform proteomic analysis to identify proteins with changed expression levels after antidepressant treatment and investigate differences in protein expression between MDD patients and healthy individuals.Methods: A total of 111 proteins obtained from literature review were subjected to multiple reaction monitoring (MRM)-based protein quantitation. Finally, seven proteins were quantified for plasma specimens of 10 healthy controls and 78 MDD patients (those at baseline and at 6 weeks after antidepressant treatment of either selective serotonin reuptake inhibitors (SSRIs) or mirtazapine). Results: Among 78 MDD patients, 35 patients were treated with SSRIs and 43 patients were treated with mirtazapine. Nineteen (54.3%) and 16 (37.2%) patients responded to SSRIs and mirtazapine, respectively. Comparing MDD patients with healthy individuals, alteration of transthyretin was observed in MDD (p = 0.026). There was no significant difference in protein levels related to SSRIs treatment. Plasma thyroxine-binding globulin (TBG) was different between before and after mirtazapine treatment only in responders (p = 0.007).Conclusions: In proteomic analysis of plasma specimens from MDD patients, transthyretin and TBG levels were altered in MDD and changed after antidepressant treatment.
Seizure in HIV-infected Patients: Clinical Presentation, Cause and Treatment Outcome in Ethiopia: A Retrospective Study
Authors: Amare Amanuel
Published: September 2020

Background: The estimated number of adult patients living with HIV infection in Ethiopia in 2012 was approximately 800,000. Seizure occurs in 2 to 3 % and 6.1 % to 34.3% in patients with HIV infection and patients with neurological complications of HIV infection, respectively. Studies on HIV infection and seizure are rare in Ethiopia. The purpose of this study was to assess clinical presentation, cause and treatment outcome of patients with HIV infection presented with seizure. Methods: In this retrospective study, patients aged ≥ 13 years with HIV infection presented with seizure were included. Medical records were reviewed and demographic and clinical data were collected.Results: Records of 146 patients were analysed. Males were 55.5% and the mean age was 34 years. The diagnosis of HIV infection was made after current hospital admission in 69% of patients. Almost all patients (98.6 %) had stage 4 HIV infection with very low CD4 count (mean = 77/mm3). In almost all patients seizure was a recent onset at current admission; either it started after admission (42.5%) or within 3 months prior to admission (52.5%). The types of seizures were: generalized tonic-clonic seizure [GTCS] (69.2%), focal motor with secondarily generalization [FMWSG] (19.9%) and simple focal motor (11%). The common causes of seizure were: cerebral toxoplasmosis (46%), tuberculous meningitis (35.6%) and cryptococcal meningitis (13.7%). Case-fatality was 53% and predictors of mortality were: seizure started after admission, change in mentation and comatose at initial evaluation. Conclusions: Most patients had stage 4 HIV infection with very low CD4 count and a recent onset seizure which started within 3 months at initial evaluation. GTCS was the commonest seizure type and most causes of seizure were central nervous system opportunistic infections. The case-fatality was high and change in sensorium was an independent predictor of mortality. To prevent the high mortality and morbidity prevention of HIV infection, early diagnosis and treatment, improving diagnostic facilities and access to non-enzyme inducing antiepileptic drugs are recommended.
Bone Marrow Dosimetric Analysis of Lymphopenia in Patients With Esophageal Squamous Cell Carcinoma Treated With Chemoradiotherapy
Authors: Wang Qian , Qiu Qingtao , Zhang Zicheng , Zhang Jing , Yang Guanghui , Liu Chengxin , Li Baosheng
Published: September 2020

Background: Lymphocytes as a marker of immune function are essential to the immune response. Sternum and vertebra bone marrow (BM) exposed to radiation may affect lymphocytes during radiotherapy (RT) for esophageal carcinoma (EC). We analyzed the relationship among peripheral blood lymphocytes, exposed sternum and vertebra body BM, and overall survival (OS) to find BM dosimetric parameters of lymphopenia during chemoradiotherapy (CRT) for patients with esophageal squamous cell carcinoma (ESCC). Methods: We examined 476 ESCC patients from January 2012 to January 2015, all of whom received concurrent or sequential CRT. Absolute lymphocyte counts (ALC) during RT of each patient were collected from the routine workup at the following RT times: pretreatment ALC (ALC0), at 1–5, 6–10, 11–15, 16–20, and 21–25, and more than 26 sessions (called ALC1–6, respectively). The sternum and vertebral body BM were delineated in accordance with uniform standards, and the irradiated volumes were calculated by dose-volume histograms (DVH). The Kaplan–Meier method and Cox proportional hazards regression were used to analyze the survival of the patients. Comparisons of DVH were performed using the Mann–Whitney U test or two-sample t-test where appropriate. Results: A relative volume of sternum BM irradiated by more than 20 Gy could clearly affect the peripheral blood lymphocytes. The V20 of sternum BM and V50 of vertebra body BM were related to the OS of the patients, and the level of ALC2(at 6–10 times of RT) could predict the patients’ outcomes. The Cox regression analyses showed that the 218 patients with ALC2 ≥ 0.8×109/L had a significantly longer OS (47.0 vs. 30.9, p<0.0001) than the 258 patients with ALC2 < 0.8×109/L. Conclusion: In patients with ESCC, the relative volume of sternum BM irradiated by more than 20 Gy was associated with lymphocyte. The V20 of the sternum BM and the V50 of the vertebra body BM were related to the OS of the patients. The level of ALC2 is a significant prognostic factor in esophageal carcinoma patients.
Application of TEM: Dynamic changes of AKAP95-Cx43 complex during G1 phase of lung cancer cells
Authors: Deng Zifeng , Liu Rong , Guo Huiling , Yao Luming , Ruan FengKai , Wang Kai , Qiu Guihua , Luo Zhen , Luo Guangping , Guo DongBei , Yao Youliang , Zhang Yongxing
Published: September 2020

BackgroundAKAP95(A-kinase anchoring protein) and Cx43 (connexin 43) express abnormally in lung cancer cells. As potential tumor therapeutic targets, specific process of bindings and dynamic changes of Cx43-AKAP95 complex in lung cancer cells may guide further treatments and detections of lung cancer. However, the process remains unclear now. We are aiming at investigating the dynamic changes of expression, localization, and binding of AKAP95 and Cx43, as well as their interaction with cyclin D1 and cyclin E1 in lung cancer cells during G1 phase.MethodsA549 and Beas-2B cells were arrested at preliminary stage(P), middle stage(M) and restriction point(R) of G1 phase and Western blot(WB), Confocal laser scanning microscopy (CLSM) and Transmission electron microscope (TEM) were used in our study to detect proteins to provide further evidence of the correlation of these proteins.Results: 1) AKAP95 carries Cx43 into the nucleus through the nuclear pore by binding to it during G1 phase. Some AKAP95 and Cx43 can aggregate and form larger protein aggregates. The process happens mainly during R stage. 2) AKAP95 and Cx43 mainly bind to cyclin D1 during P and M stage while bind to cyclin E1 during R stage respectively. Complexes of AKAP95-cyclin D1 and Cx43-cyclin D1 cannot enter nucleus while AKAP95-cyclin E1 and Cx43-cyclin E1 can.Conclusions1) Binding process of AKAP95-Cx43 complexes/ aggregates can be summarize as ‘bind and aggregate -target and enter nucleus- keep binding/aggregating in nucleus’. 2) Cyclin E1 was involved in the binding/aggregation and nuclear entry of AKAP95 and Cx43 while cyclin D1 only binds to them respectively in the cytoplasm.
The feasibility and reliability of actigraphy to monitor sleep in intensive care patients: An observational study
Authors: Delaney L.J. , Litton E. , Melehan K.L , Huang H-C.C , Lopez V , Haren F Van
Published: September 2020

Background: Sleep amongst intensive care patients is reduced and highly fragmented which may adversely impact on recovery. The current challenge for Intensive Care clinicians is identifying feasible and accurate assessments of sleep that can be widely implemented. The objective of this study was to investigate the feasibility and reliability of a minimally invasive sleep monitoring technique compared to the gold standard, polysomnography, for sleep monitoring. Methods: Prospective observational study employing a within subject design in adult patients admitted to an Intensive Care Unit. Sleep monitoring was undertaken amongst minimally sedated patients via concurrent polysomnography and actigraphy monitoring over a 24-hour duration to assess agreement between the two methods; total sleep time and wake time. Results: We recruited 80 patients who were mechanically ventilated (24%) and non-ventilated (76%) within the intensive care unit. Sleep was found to be highly fragmented, composed of numerous sleep bouts and characterized by abnormal sleep architecture. Actigraphy was found to have a moderate level of overall agreement in identifying sleep and wake states with polysomnography (69.4%; K = 0.386, p < 0.05) in an epoch by epoch analysis, with a moderate level of sensitivity (65.5%) and specificity (76.1%). Monitoring accuracy via actigraphy was improved amongst non-ventilated patients (specificity 83.7%; sensitivity 56.7%). Actigraphy was found to have a moderate correlation with polysomnography reported total sleep time (r = 0.359, p < 0.05) and wakefulness (r = 0.371 p < 0.05). Bland-Altman plots indicated that sleep was underestimated by actigraphy, with wakeful states overestimated. Conclusions: Actigraphy was easy and safe to use, provided moderate level of agreement with polysomnography in distinguishing between sleep and wakeful states, and may be a reasonable alternative to measure sleep in intensive care patients. Clinical Trial Registration number: ACTRN12615000945527 (Registered 9/9/2015)
Improvement of Urinary Tract Symptoms and Quality of Life in Benign Prostate Hyperplasia Patients, Associated with Consumption of a Newly Developed whole Tomato Based Food Supplement. A phase II prospective, Randomized Double-blinded, Placebo-controlled Study.
Authors: Cormio Luigi , Calò Beppe , Iezzi Manuela , Lamolinara Alessia , Vitaglione Paola , Silecchia Giovanni , Carrieri Giuseppe , Fogliano Vincenzo , Iacobelli Stefano , Natali Pier Giorgio , Piantelli Mauro
Published: September 2020

Background: Benign prostatic hyperplasia is the most common urologic disease among elderly men. The diagnosis of BPH is usually in response to the appearance of lower urinary tract obstructive, and post-micturition symptoms (LUTS) that can significantly affect the quality of life. In Aim of this study was to evaluate in a phase II prospective, randomized double-blinded, placebo-controlled study, the efficacy and safety of a novel whole tomato-based food supplement on LUTS of patients affected by benign prostatic hyperplasia. Methods: Thirty-four consecutive patients with histologically proved BPH were included in a phase II prospective, randomized double-blinded, placebo-controlled study. Patients were randomized to receive daily for two months a sachet (5 grams) of the tomato-based food supplement Lycoprozen® or an identical sachet containing placebo. Patients were asked to fill the “International Prostatic Symptom Score” questionnaire before and after treatment. Results: All patients successfully completed the scheduled regimen. No side effects were recorded. Lycoprozen® significantly reduced the LUTS severity. Particularly, the IPSS mean values before and after the treatment were 7.5+1.1 SE (range 16-2) and 5.1+1.0 SD (range 14-2), respectively (paired t-test, two-tailed p value <0.0002). A trend toward a reduction of total PSA levels was observed in Lycoprozen® treated patients (9.346 ng/ml+1.839 SE vs.7.906+0.928 SE, P = 0.096) (Fig 1, left). This trend was sustained by the significant reduction of PSA levels seen in 5 patients, (2 obese, 2 over-weight and 1 normal-weight) with basal levels >10 ng/ml (18.520ng/ml+2.747 SE vs. 10.323ng/ml+2.073 SE, P = 0.009)
Predictive value of HMGB1 for atrial fibrillation recurrence after catheter ablation in paroxysmal atrial fibrillation patients
Authors: Li Xin-xin , Zhao Cui-ting , Li Meng , Yu Hong-xiao , Liu Xi-ping , Zhu Qing , Song Xiao-kun , Wang Yong-huai , Yu Bo , Ma Chun-yan
Published: September 2020

Background: To evaluate the clinical efficacy of serum high-mobility group box-1 (HMGB1) released from the left atrium to predict atrial fibrillation (AF) recurrence in paroxysmal AF (pAF) patients after catheter ablation (CA) at 1-year follow-up.Methods: We included 72 pAF patients who underwent CA. To determine the expression levels of HMGB1, left atrial blood samples were collected from the patients prior to CA and after the procedure through the transseptal sheath placed into the left atrium. Patients were followed-up for AF recurrence after 1 year of CA.Results: A total of 19 (26%) patients of the 72 experienced AF recurrence. No significant differences were noted in the clinical baseline data between the AF recurrence and AF nonrecurrence groups. The level of postoperative HMGB1 (HMGB1post) was higher in the AF recurrence group than in the AF nonrecurrence group (298.51µg/L vs. 278.17 µg/L; P = 0.03). However, no differences were noted in the levels of other biomarkers such as preoperative high-sensitivity C-reactive protein (hs-CRPpre), postoperative hs-CRP (hs-CRPpost), and preoperative HMGB1 (HMGB1pre) between the two groups. Multiple logistic regression analysis revealed that a higher level of serum HMGB1post from the left atrium (HMGB1post: ≥279.35 µg/L) was an independent predictor of AF recurrence (odds ratio [OR]: 5.29 [1.17–23.92], P = 0.04). Receiver operating characteristic (ROC) analysis revealed that HMGB1post had a moderate predictive power for AF recurrence (area under the curve [AUC]: 0.68; sensitivity: 72%; specificity: 68%). The 1-year AF-free survival was significantly lower in patients with a high serum HMGB1post level than in those with a low HMGB1post level (hazard ratio [HR]: 3.81 [1.49–9.75], P = 0.005).Conclusion: In pAF patients who underwent CA, the level of HMGB1 from the left atrium immediately after CA was associated with AF recurrence and demonstrated a moderate predictive power. Thus, we offer a potential predictor to identify pAF patients at high risk of AF recurrence.
The Involvement of Neuroimmune Cells in Adipose Innervation
Authors: Blaszkiewicz Magdalena , Wood Elizabeth , Koizar Sigi , Willows Jake , Anderson Ryan , Tseng Yu-Hua , Godwin James , Townsend Kristy L.
Published: September 2020

Background: Innervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and ‘browning’ of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration and plasticity, including neurite outgrowth and synapse formation. Peripheral blood immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose immune cells secrete brain derived neurotrophic factor (BDNF). Methods: We now show that deletion of this neurotrophic factor from the myeloid lineage led to a ‘genetic denervation’ of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation. Results: We and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C + CCR2 + Cx3CR1 + monocytes/macrophages that express noradrenergic receptors and BDNF. Conclusions: We propose that these cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure.
Mycobacterium Tuberculosis Thymidylate Kinase is A Potential 2 Diagnostic Biomarker for Pulmonary Tuberculosis
Authors: Babirye Janet Peace , Kato Charles Drago , Lutwama Fredrick , Musubika Carol , Nabatanzi Rose , Wayengera Misaki
Published: September 2020

Diagnosis of pulmonary tuberculosis (PTB) in context of HIV infection remains challenging due 25 to the paucibacillary nature of the disease. Mycobacterium tuberculosis thymidylate kinase 26 (TMKmt) has been validated as a novel biomarker with high detection limits for PTB in sputum. 27 We aimed to clinically test TMKmt as a diagnostic biomarker for pulmonary tuberculosis among 28 HIV positive individuals at Makerere University Joint AIDS Program Immuno Suppression 29 Syndrome clinic. 30 Methods 31 A total of 120 participants with presumptive PTB were enrolled in a cross- sectional study 32 between January and September 2018. Venous blood and expectorated spot sputum was obtained 33 from 116 consenting participants. Tuberculosis culture was performed on sputum as the gold 34 standard to confirm PTB status while direct ELISAs were performed on sputum and serum to 35 determine the level of TMKmt antigen. Sensitivity, specificity and receiver operator 36 characteristic curves were used to assess the precision of TMKmt in diagnosing PTB. 37 Results 38 Of the 116 participants, only 22 (19%) were PTB positive based on either Lowenstein Jensen or 39 Mycobacterial growth inhibition tube `culture. The mean sputum TMKmt levels were 40 significantly higher in PTB positive individuals (4.889 ± 0.135) ng/ml as compared to PTB 41 negative individuals (4.303 ± 0.07295) ng/ml (t-test, P<0.0005). At a cut off value of > 4.683 42 ng/ml, the test had a sensitivity of 73% (95% CI, 49.78% - 89.27%) and a specificity of 72% 43 (95% CI, 62.15% - 81.07%). These results were supported by a receiver operator analysis which 44 showed an area under the curve of 0.75 (95% CI, 0.63 – O.86). 3 45 Conclusion 46 Sputum TMKmt is a potential diagnostic biomarker for active pulmonary tuberculosis. This 47 forms an alternate test that would replace smear microscopy and overcome the current TB 48 diagnostic challenges.
Molecular Characterization of Budgerigar Fledgling Disease Virus SC-YB19, with an 18-Nucleotides Deletion, in China
Authors: Zhi-ge Tian , Chuan-ming Yin , Feng Cong , hu xiaoliang
Published: September 2020

Background: Budgerigar fledgling disease virus (BFDV) poses a serious threat to the Chinese psittacine industry, causing enormous economic losses. This study aims to reveal the etiological role of BFDV and evaluate the molecular characterization.Results: We report on BFDV, designated SC-YB19, which had an 18-nucleotide (nt) deletion in the enhancer region, corresponding to the sequence position 164–181 nt, when compared with other BFDV strains. Sequence analyses suggested that 19 nucleotide substitutions were identified with the domestic strains, APV7 and AF118150. Phylogenetic analysis indicated that SC-YB19, along with three domestic strains, formed a unique cluster, and were closely related to Polish isolates. Conclusion: Taken together, these results demonstrate that a BFDV genotype variation was co-circulating in China, and provide important insights on evolution of BFDV.