bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of integrated geriatric outpatient clinic on the health care utility of elderly
Authors: WEI YU-JU , Hsieh Cheng-Fang , Huang Yu-Ting , Huang Ming-Shyan , Fang Tzu-Jung
Published: January 2020

Background: People above age 65 are growing in many countries. Taiwan will be a super-aged society in 2026 and the utility of health care will increase considerably. Our study was aimed to evaluate the efficacy of the geriatric integrated outpatient clinic on health care utility reduction of the elderly. Methods: This was a retrospective case-control study. The patients with age more than 65 years old in the geriatric outpatient clinic (Geri-OPD) and non-geriatric outpatient clinic (non-Geri OPD) with age and sex-matched in a single medical center were included. The numbers of outpatient clinic visits, emergency department visits, hospitalization, and medical expenditure data were collected in the first year and second year. The subgroup analysis by Charlson comorbidity index (CCI) and older age (age≧80 years old) was done between Geri-OPD and non-Geri OPD. Results: Total 6723 patients were included (3796 women and 2927 men). The mean age was 80.42 ± 6.39 years old. There were 1291 (19.2%) patients from the Geri-OPD and 5432 (80.8%) patients from the non-Geri OPD. After one year regular follow-up, those Geri-OPD patients had significantly reduced 5.62±10.85 kinds of drugs in each prescription and 18.18 ± 48.85 clinic visits per year (P<0.01). After two-year follow-up, the clinic visits, emergent department visits, hospitalizations, and the annual medical cost still decreased in the Geri-OPD patients. The Geri-OPD patients have more co-morbidities and higher health care utility than the non-Geri OPD patients. In the subgroup analysis, the patients with higher comorbidities (CCI≧2) and older age (≧80 years old) have significant health care utility reduction in Geri-OPD. The medical utility difference between the Geri-OPD and non-Geri OPD patients also decreased significantly. Conclusion: The geriatric integrated outpatient clinic reduced the medical cost, drug numbers, and the frequency of outpatient clinic visit, emergency department visit and hospitalization in the complicated elder patients. The effect was even better in the second year.
The erosion of ambiguity tolerance and sustainment of perfectionism in undergraduate Medical training: A study of clerkship training effects.
Authors: Ndoja Silvio , Chahine Saad , Saklofske Donald H. , Lanting Brent
Published: January 2020

Background : Medicine is a field that is simultaneously factual and ambiguous. While studies have examined medical trainees’ tolerance of ambiguity (TOA), the extent to which TOA is affected by clinical experiences and its association with other psychological factors such as perfectionism is unknown.
Methods: This was a single cohort study:174 Students in the first (pre) and last (post) 12 weeks of their 3 rd year comprising of 6 core rotations were invited to participate in an online anonymous survey. The survey included demographic information along with published and validated TOA and perfectionism scales. Tolerance of Ambiguity in Medical Students and Doctors (TAMSAD) and The Big Three perfectionism scale-short form (BTPS-SF) were used to assess TOA and perfectionism respectively. Pre-Post mean comparisons and correlations were used to detect the effect of clerkship on TOA, perfectionism and their relationship.
Results: 51 students responded to pre-survey, 62 responded to post-survey. Clerkship was associated with a decrease TOA (p<0.00) with pre-TOA scores at m=59.57 and post TOA at m=43.8. There was a moderate inverse correlation between TOA and perfectionism before clerkship (r=0.32) that increased slightly after clerkship (r=0.39). Clerkship was not significantly associated with levels of perfectionism (P>0.05). Those preferring primary care specialties had significantly lower rigid and total perfectionism scores in pre clerkship than those choosing other specialties, this difference was not found post clerkship.
Conclusion: Clerkship does appear to influence student’s tolerance of ambiguity. However, perfectionism remained unchanged. Further work needs to be done exploring tailoring educational interventions to extremes of TOA and perfectionism.
Medical Education Interest, Exposure, and Career Planning in Subspecialty Trainees
Authors: Marshall Ariela L , Thompson Carrie A. , Cullen Michael W. , Raffals Laura E. , Oxentenko Amy S.
Published: January 2020

Background Medical education encompasses many activities (e.g., teaching, supervision, mentorship, and administration). Little research has explored what the term "medical education" means to trainees or assessed the importance postgraduate medical trainees place on education as part of their career plans. Methods We conducted a survey of fellows in all subspecialty training programs at a three-site academic institution. We asked multiple choice and Likert scale questions to characterize fellows’ perception of, interest and training in medical education. Results One hundred sixty-nine of 530 (31.9%) fellows responded. Fellows were training in subspecialties of internal medicine (49.7%) and surgery (13.0%), among others. Most fellows planned careers in academic medicine (38.5% clinician-educator, 22.5% clinician-investigator, 17.2% academic clinician). Fellows reported that their conception of medical education involved supervising trainees in a clinical capacity (93.5%), teaching in the classroom (89.3%), and providing mentorship for trainees (87.6%). Respondents identified “being an educator” as extremely (43.8%) or moderately (43.2%) important for their future careers. Only 30.2% had received formal training in medical education, but 61.5% felt that formal training should be required for those pursuing careers with strong educational components. Conclusions Most subspecialty fellows surveyed planned careers in academics and felt that medical education was important to their professional future. While less than a third received formal training in education, almost two thirds felt that such training should be required for a career as an educator. This study provides evidence for the creation and promotion of educational training programs for trainees interested in careers involving medical education.
Persons post-stroke restore step length symmetry by walking asymmetrically
Authors: Padmanabhan Purnima , Sreekanth Keerthana , Gulhar Shivam , Cherry-Allen Kendra M. , Leech Kristan A. , Roemmich Ryan T.
Published: January 2020

Background: Restoration of step length symmetry is a common rehabilitation goal after stroke. Persons post-stroke often retain the ability to walk with symmetric step lengths (“symmetric steps”); however, the resulting walking pattern remains effortful. Two key questions with direct implications for rehabilitation have emerged: 1) how do persons post-stroke generate symmetric steps, and 2) why do symmetric steps remain so effortful? The objective of this study was to understand how persons post-stroke generate symmetric steps and how the resulting gait pattern relates to the metabolic cost of transport. Methods: We recorded kinematic, kinetic, and metabolic data as ten persons post-stroke walked on an instrumented treadmill under two conditions: preferred walking and symmetric stepping (using visual feedback).Results: Persons post-stroke restored step length symmetry using energetically costly, asymmetric patterns. Impaired paretic propulsion and abnormal vertical movement of the center of mass were evident during both preferred walking and symmetric stepping. These deficits contributed to diminished positive work performed by the paretic limb on the center of mass in both conditions. Decreased positive paretic work correlated with increased metabolic cost of transport, decreased self-selected walking speed, and increased asymmetry in limb kinematics.Conclusions: It is critical to consider the mechanics used to restore symmetric steps when designing interventions to improve walking after stroke. Facilitating symmetric steps via increased paretic propulsion or enabling paretic limb advancement without excessive vertical movement may enable persons post-stroke to walk with a less effortful gait pattern.
SPOP accelerates acute myeloid leukemia initiation and development through miR-183-mediated METAP2 inhibition
Authors: Yu Jifeng , Li Yingmei , Sun Ling , Han Lijie , Liu Yu , Zhang Danfeng , Xing Haizhou , Xie Xinsheng , Wan Dingming , Jiang Zhongxing
Published: January 2020

Background: Recent miRNA profiling studies have implicated the potential use of miRNAs as as diagnostic and prognostic indicators in acute myeloid leukemia (AML), which has been reportedly implicated in the interplay with certain mRNAs. Herein this study, we intend to characterize the functional relevance of SPOP/miR-183/METAP2 axis in AML in vivo and in vitro. Methods: Differentially expressed mRNAs and downstream regulatory miRNA were predicted by in silico analysis. We induced SPOP/miR-183/METAP2 overexpression or inhibition to examine their effects on AML cell proliferation and apoptosis in vitro and tumor growth in vivo , along with their interaction with β-catenin. Results: SPOP and miR-183 were highly expressed, while METAP2 was poorly expressed in patient peripheral blood samples and cell lines of AML. SPOP accelerated the proliferation of AML cells and repressed apoptosis. Mechanistically, SPOP enhanced β-catenin protein stability and nuclear translocation leading to upregulated expression of miR-183. MiR-183 facilitated proliferation and inhibited apoptosis of AML cells by targeting METAP2. Furthermore, miR-183 inhibition and METAP2 overexpression reversed SPOP-induced AML cell malignancy. Besides, in vitro findings were reproduced by in vivo findings. Conclusion: SPOP stimulated AML malignant progression by inducing β-catenin stability and miR-183/METAP2 axis activation, highlighting a potential therapeutic target against AML recurrence and metastasis.
Genetic variation in toll like Receptor 2, 7, 9 and interleukin-6 influences risk of Cytomegalovirus infection in pregnancy
Authors: Mhandire Doreen , Mhandire Kudakwashe , Magadze Mulalo , Wonkam Ambroise , Kengne Andre P , Dandara Collet
Published: January 2020

Background: Maternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans. Results: The TLR2 rs1816702C/C (p=0.002), TLR7 rs179008C/C (p<0.001) and TLR9 rs352139C/C (p=0.003) genotypes were associated with a CMV+ status. In contrast, the interleukin ( IL)-6 rs10499563T/C TLR2 rs1816702C/C (p=0.002) genotype was associated (p<0.001) with CMV- status. Furthermore, genotype and allele frequencies of SNPs in TLR2, TLR4, TLR9, TLR7 , IL - 6 , IL-10 , IL-28B , IL-1A and interferon AR1 ( IFNAR1 ) genes are being reported here in a Zimbabwean population. Conclusions: Toll like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population that was previously exposed to CMV infection.
How to equalize the leg length in total hip arthroplasty for patients with unilateral Crowe type IV developmental dysplasia of the hip
Authors: Du Yinqiao , Sun Jingyang , Ma Haiyang , Wang Sen , Ni Ming , Zhou Yonggang
Published: January 2020

Background: The purpose of this study was to explore that how to equalize the leg length in total hip arthroplasty (THA) with shortening subtrochanteric osteotomy (SSTO) or not for unilateral Crowe type IV developmental dysplasia of the hip (DDH) through the evaluation of the postoperative full-length anteroposterior radiographs. Methods: The postoperative radiographs of 60 patients with unilateral Crowe type IV DDH from July 2012 to May 2019 were retrospectively reviewed. These data included leg length, femoral length, height of center of rotation (COR) of hip, height of greater trochanter, and depth of the sleeve or cone. Patients with leg length discrepancy (LLD) < 10 mm were defined as the non-LLD group. Results: In the non LLD group (26 patients of SSTO and 22 of non-SSTO), the femoral length both SSTO and non-SSTO groups were significantly shorter on operated side, compared with the contralateral side, and the mean discrepancy in SSTO group was approximately equal to the mean length of SSTO. The mean height of COR of hip on operated sides both SSTO and non-SSTO groups were 13.2 mm, and the contralateral sides were 15.2 mm and 15.5 mm, respectively. The depth of the sleeve or cone between SSTO and non-SSTO groups were 21.7 mm and 30.6 mm, respectively. The depth of the sleeve or cone in SSTO group was negatively correlated with the length of SSTO. The height of the greater trochanter of the operated and contralateral sides were 5.3 mm and 16.6 mm in SSTO group, and those in the non-SSTO group were 13.2 mm and 17.2 mm. Conclusions: SSTO leaded to femoral shortening on the operated side for patients with unilateral Crowe type IV DDH. The position of sleeve or cone should be close to the apex of greater trochanter to compensate the lengh of SSTO.
Valgus Stability is Enhanced by Flexor Digitorum Superficialis Muscle Contraction of the Index and Middle Fingers
Authors: Hoshika Shota , Nimura Akimoto , Takahashi Norimasa , Sugaya Hiroyuki , Akita Keiichi
Published: January 2020

Background: Flexor digitorum superficialis (FDS) muscle provides dynamic stabilization and medial elbow support for ulnar collateral ligament (UCL). The FDS contraction significantly affects the medial joint distance (MJD) through grip contraction. However, it remains unclear whether FDS activity alone contributes to medial elbow stability, or together with the activation of the flexor digitorum profundus during grip contraction, and which finger’s FDS is the main contributor to elbow stability. We investigated the resistive effects of isolated FDS contraction in individual fingers against valgus stress in the elbow joint using stress ultrasonography (US). Methods: We investigated 17 healthy males (mean age, 27 ± 5 years). Valgus stress US was performed using the Telos device, with the elbow at 30° flexion. MJD was measured for each arm during 3 separate conditions: at rest (unloaded), under valgus load (50 N) (loaded), and under valgus load with FDS contracted in individual fingers (loaded-contracted). Results : MJD was significantly longer when loaded (5.4 ± 0.4 mm) than unloaded (4.1 ± 0.2 mm, P = .007 ) or loaded-contracted (4.6 ± 0.3 mm, P = .003 ) for each finger. When loaded-contracted, MJD differed statistically between the index and ring fingers ( P = .03 ) and between the middle and ring fingers ( P = .04 ). However, the difference between the index and middle fingers was not statistically significant ( P = . 08 ). Conclusion s : Individual FDS contraction, particularly of the index and middle fingers contributes most to stabilization against valgus stress. Thus, injury care programs should incorporate FDS exercises of these fingers.
An Order Independent Algorithm for Inferring Gene Regulatory Network Using Quantile Value for Conditional Independent Tests
Authors: Mahmoodi Mir Hadi , Aghdam Rosa , Eslahchi Changiz
Published: January 2020

Background: In recent years, due to the difficulty and inefficiency of experimental methods, numerous computational methods have been introduced for inferring structure of Gene Regulatory Networks (GRNs). Bayesian network is one of the popular methods in this field, however, still has many drawbacks and there is still a great space to be improved. For example, the Path Consistency (PC)-based algorithms as Bayesian network methods are still sensitive to the ordering of nodes i.e. different node orders results in different network structures. The second is that the networks inferred by these methods are highly dependent on the threshold used for independence testing. Also, it is still a challenge to select the set of conditional genes in an optimal way, which affects the performance and computation complexity of the PC-based algorithm. Results: We introduce a novel algorithm, namely Order Independent PC-based algorithm using Quantile value (OIPCQ), which improves the accuracy of the learning process of GRNs and solves the order dependency issue. The quantile-based thresholds are considered for different order of CMI test. For conditional gene selection, we consider the paths between genes with length equal or greater than 2 while others well-known PC-based methods only considers the paths of length 2. We applied OIPCQ on the various networks of the DREAM3 and DREAM4 in silico challenges. As a real-world case study, we used OIPCQ to reconstruct SOS DNA network obtained from Escherichia coli and GRN for acute myeloid leukemia based on the RNA sequencing data from The Cancer Genome Atlas. The results show that OIPCQ produces the same network structure for all the permutations of the genes and improves the resulted GRN through accurately quantifying the causal regulation strength in comparison with others well-known PC-based methods. Conclusions: According to the GRN constructed by OIPCQ, for acute myeloid leukemia, two regulators BCLAF1 and NRSF reported by Zhang et al are significantly important. However, the highest degree nodes in this GRN are ZBTB7A and PU1 which play a significant role in cancer, and especially in leukemia. OIPCQ is freely accessible at https://github.com/haammim/OIPCQ-and-OIPCQ2.
Analysis of the Effect of Rural Residents Serious Illness Medical Insurance on Relieving the Economic Burden of Rural Residents in China:A Case Study in Jinzhai County
Authors: Li Yang , Duan Guangfeng , Xiong Linping
Published: January 2020

Background In 2003, China established a New Rural Cooperative Medical System(NRCMS) for rural residents, which had alleviated the burden of medical expenses of rural residents, but the reimbursement for high medical was insufficient. Therefore, China had gradually established a Serious Illness Insurance System (SIMIS) on the basis of NRCMS. After the payment of NRCMS, patients who met the requirements of SIMIS policy would be given a second payment to further alleviate the economic burden of patients with high medical expenses in rural areas. The purpose of this study is to analyze the effect of the implementation of SIMIS on alleviating the economic burden of rural residents in Jinzhai County. Methods Based on the inpatient reimbursement data of NRCMS in Jinzhai County, Anhui Province from 2013 to 2016. We adopt descriptive and regression discontinuity (RD) method to analyze the payment effect of SIMIS. The RD analysis object (n = 7353) was the patients whose annual serious illness expenses were between CNY 10,000 and CNY 30,000, and the descriptive analysis object (n = 2720) was the patients compensated by SIMIS. Results The results of RD showed that the actual medical insurance payment proportion (AMIPP) increased by about 2.5% (lwald = 0.025, P < 0.01), inside medical insurance self-payment proportion (IMSPP) increased by about 2% (lwald = 0.020, P < 0.10), outside medical insurance self-payment proportion (OMISPP) decreased by about 1.6% (lwald = -0.016, P < 0.05). The descriptive results showed that the serious illness patients mostly chose to go to hospital outside the county. The annual average number of hospitalizations was 3.64. The reimbursement mainly came from the NRCMS. The payment amount of SIMIS was relatively small, and the out of pocket medical expenses were still high. Conclusion The medical technology level of Jinzhai County could not meet the needs of seriously illness patients, the number of beneficiaries of SIMIS was small, and the ability to relieve the burden of medical expenses of rural residents was insufficient. The high out of pocket expenses increased the possibility that people with good economic conditions could enjoy the reimbursement of SIMIS, resulting in inequity.
Evaluation of an integrated health and livelihood development program for marginalized communities in India
Authors: Sharma Shantanu , Akhtar Faiyaz , Singh Rajesh Kumar , Mehra Sunil
Published: January 2020

Background: Women from marginalized communities have poorer maternal health outcomes and limited utilization of health services compared to other communities. There is empirical evidence that comprehensively designed interventions targeting health education of women and social determinants of health, such as financial security, have better outcomes than focusing on health education alone. A community-based intervention was implemented to improve maternal, child, and adolescent health practices in marginalized communities. Besides, the project aimed to promote financial literacy and enhance livelihood opportunities for young people. This three-year peer-led intervention was done in the two districts of Rajasthan, namely Nagaur and Pali. The paper aimed at assessing the effectiveness of this community-based intervention. Methods: Pre-post study design based on qualitative research was used for the evaluation of the intervention. Purposive sampling was done both at baseline and the end-line assessments. Focus group discussions were done with women (15-49 years) and adolescents (10-19 years), and in-depth interviews with frontline workers and village health committees were done. Content analysis was done. Results: Overall, 4853 women, and 8158 adolescents were engaged in the intervention in two districts. We found a noticeable change in some of the practices like institutional delivery, breastfeeding, uptake of antenatal care among women, and knowledge about sexual and reproductive health among adolescents. Around 23% and 67% of the young people from Nagaur and Pali, respectively, were linked with jobs in computer training centers, tailoring centers, and beauty parlors. However, we found a lack of change in some of the indicators, such as knowledge about HIV testing during pregnancy, uptake of contraceptives, and iron-folic acid consumption among women. Early marriage was widely prevalent in the districts, the reduction of which was underachieved. In the interviews, frontline workers reported having been impartial and inclusive in delivering health services. Conclusions: We found evidence suggesting that peer-led interventions are equally effective in improving maternal and child health practices and livelihood promotion. The gaps at system-level, coupled with the presence of specific socio-cultural contextual factors might explain for lack of improvement in some of the indicators.
Novel homozygous HEXB mutation identified in a consanguineous Iranian pedigree with Sandhoff disease
Authors: Rahmani Zahra , Banisadr Arsham , Ghodsinezhad Vadieh , Dibaj Mohsen , Aryani Omid
Published: January 2020

Background Sandhoff disease is a rare neurodegenerative and autosomal recessive disorder, characterized by a defect in ganglioside metabolism. It is caused by mutations in the HEXB gene for the β-subunit of β-N-acetyl hexosaminidase. Results In the present study, an Iranian 14- month -old girl with an 8- month history of unsteady walking and involuntary movements is described. Biochemical testing showed defects in the normal activity of beta-hexosaminidase protein. Following sequencing of HEXB gene, a novel homozygous p.A278V mutation was identified in the patient’s DNA. Conclusions The p.A278V mutation is pathogenic because of amino acid change and changing in biochemical activity. this mutation has not been reported previously, but based on In silico analysis and structural analysis, was predicted to be disease causing.
Adult spinal deformity and its relationship with height loss: A 34-year longitudinal cohort study
Authors: Shimizu Mutsuya , Kobayashi Tetsuya , Chiba Hisashi , Senoo Issei , Ito Hiroshi , Matsukura Keisuke , Saito Senri
Published: January 2020

Background Age-related height loss is a normal physical change that occurs in all individuals over 50 years of age. Many epidemiological studies were conducted on height loss worldwide, however, over the 30 years longitudinal epidemiological studies have not been conducted. This study was designed to investigate changes in adult spinal deformity and examine the relationship between adult spinal deformity and height loss. Methods Fifty-three local healthy subjects (32 men, 21 women) from Furano, Hokkaido, Japan, volunteered for this longitudinal cohort study. Their heights were measured in 1983 and again in 2017. Spino-pelvic parameters were compared between 1983 and 2017. Individuals with height loss were then divided into two groups, those with degenerative spondylosis and those with degenerative lumbar scoliosis, and different characteristics were compared between the two groups. Results The mean age of the subjects was 44.4 (31-55) years at baseline and 78.6 (65-89) years at the final follow-up. The mean height was 157.4 cm at baseline and 153.6 cm at the final follow-up, with a mean height loss of 3.8 cm over 34.2 years. All parameters except for thoracic kyphosis were significantly different between 1983 and 2017 (p<0.05). Height loss was related to changes in pelvic parameters including pelvic incidence-lumbar lordosis (R=0.553 p<0.0001), pelvic tilt (R=0.462 p<0.0001), and sagittal vertical axis (R=0.514 p<0.0001). Greater height loss was more commonly seen in women (p=0.001) and in patients with degenerative lumbar scoliosis (p=0.02). Conclusions This longitudinal study revealed that height loss is more commonly observed in women and is associated with adult spinal deformity and degenerative lumbar scoliosis. Height loss is a normal physical change with aging, but excessive height loss is due to spinal kyphosis and scoliosis leading to spinal malalignment. Our findings suggest that height loss might be an early physical symptom for spinal malalignment.
Association between hip muscle cross-sectional area and hip pain and function in individuals with mild-to-moderate hip osteoarthritis: a cross-sectional study.
Authors: Peiris Waruna , Cicuttini Flavia M , Constantinou Maria , Yaqobi Abbas , Hussain Sultana Monira , Wluka Anita E , Urquhart Donna , Barrett Rod , Kennedy Ben , Wang Yuanyuan
Published: January 2020

Objective: To examine the associations between hip muscle cross-sectional area and hip pain and function in community-based individuals with mild-to-moderate hip osteoarthritis. Methods: This study included 27 participants with mild-to-moderate hip osteoarthritis. Cross-sectional area of hip muscles, including psoas major, rectus femoris, gluteus maximus, gluteus medius and minimus, adductor longus and magnus, obturator internus, and obturator externus, were measured from magnetic resonance images. Hip pain and function were evaluated using the Hip Disability and Osteoarthritis Outcome Score (HOOS). Results: After adjusting for age and gender, greater cross-sectional area of adductor longus and magnus was associated with a higher HOOS score in quality of life (regression coefficient 1.4, 95% confidence interval (CI) 0.2-2.7, p=0.02), activity of daily living (regression coefficient 1.3, 95% CI 0.1-2.6, p=0.04) and sport and recreation function (regression coefficient 1.6, 95% CI 0.1-3.0, p=0.04). Greater cross-sectional area of psoas major was associated with a higher quality of life score (regression coefficient 3.6, 95% CI -0.5 to 7.7, p=0.08). The cross-sectional area of hip muscles was not significantly associated with HOOS pain or symptom score. Conclusion: Greater cross-sectional area of hip adductors was associated with better function and quality of life in individuals with mild-to-moderate hip osteoarthritis. Greater cross-sectional area of hip flexors might be associated with better quality of life. These findings, while need to be confirmed in longitudinal studies, suggest that targeting the hip adductor and flexor muscles may improve function and quality of life in those with mild-to-moderate hip osteoarthritis.
Trends in Mycobacterium Tuberculosis and prevalence of Rifampicin Resistance in Eastern zone, Tigray Region, Northern Ethiopia
Authors: Kahsu Getachew Abay , Hailay Bahlibi
Published: January 2020

Background Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. The emergence of Mono or multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis (XDR-TB), poses a considerable challenge to Mycobacterium tuberculosis control programs in the worldwide; however, there has been no reliable and organized data on trends and prevalence drug resistance of Mycobacterium tuberculosis in study area; Therefore, aim of this study to determine the trends of Mycobacterium tuberculosis and prevalence of Rifampicin resistance in eastern zone, Tigray, Northern Ethiopia. Methods Hospital based retrospective cross-sectional study was conducted at Adigrat General Hospital from June 01 to August 30, 2019.Data was collected retrospectively from the registration books using data extraction format commence January 01, 2015, December 30, 2018. Data was entered into Epi-Info 3.1 and exported and analyzed using SPSS Version 20. The results were summarized using descriptive statistics, tables, and figures. P values < 0.05 would be considered statistically significant. Result A total of 5,944 Mycobacterium tuberculosis presumptive patients were included in the study. The majority of the study participants were male (58.1%). The median age of the participants was 40.0 (IQR 57, 26) years, the majority age-group was 30-44 years. The overall prevalence of Mycobacterium tuberculosis was 1446 (24.3%). Of the total confirmed cases, 132 (9.1%) were resistant to rifampicin. From total Rifampicin resistant 129 (97.7%) new cases and the rest were previously treated tuberculosis patients. Age, reason for diagnosis, site of presumptive tuberculosis, being HIV infected was found a significant association with our dependent variable; however, only Age and being HIV infected associated with rifampicin resistance. Conclusion In our study, the overall trends of Mycobacterium tuberculosis and prevalence of rifampicin resistance were found high and increased; therefore, maximizing early detection of drug-resistant Mycobacterium tuberculosis and strengthening TB infection control activities and proper implementation of directly observed treatment are recommended reducing the burden of this contagious disease.
The Influence of Rhizosphere Soil Fungal Diversity and Complex Community Structure to Wheat Root Rot Disease
Authors: Zhang Xuejiang , Wang Heyun , Ash Gavin , Yu Dazhao , Wang Hua
Published: January 2020

Background: Wheat root rot disease due to soil-borne fungal pathogens leads to tremendous yield losses worth billions of dollars worldwide every year. It is very important to study the relationship between rhizosphere soil fungal diversity and wheat roots to understand the occurrence and development of wheat root rot disease. Results: A significant difference in fungal diversity was observed in the rhizosphere soil of healthy and diseased wheat roots in the heading stage, but the trend was the opposite in the filling stage. The abundance of most genera with high richness decreased significantly from the heading to the filling stage in the diseased groups; the richness of approximately one-third of all genera remained unchanged, and only a few low-richness genera, such as Fusarium and Ceratobasidium, had a very significant increase from the heading to the filling stage. In the healthy groups, the abundance of most genera increased significantly from the heading to the filling stage; the abundance of some genera did not change markedly, or the abundance of very few genera increased significantly. Physical and chemical soil indicators showed that low soil pH and density, increases in ammonium nitrogen, nitrate nitrogen and total nitrogen contributed to the occurrence of wheat root rot disease. Conclusions: Our results revealed that in the early stages of disease, highly diverse rhizosphere soil fungi and a complex community structure can easily cause wheat root rot disease. The existence of pathogenic fungi is a necessary condition for wheat root rot disease, but the richness of pathogenic fungi is not necessarily important. The increases in ammonium nitrogen, nitrate nitrogen and total nitrogen contributed to the occurrence of wheat root rot disease. Low soil pH and soil density are beneficial to the occurrence of wheat root rot disease. Keywords: Rhizosphere soil, Fungal diversity, Community structure, Wheat root rot disease
Characteristics of persistent hotspots of Schistosoma mansoni in western Côte d’Ivoire
Authors: Assaré Rufin Kouassi , N’Tamon Roméo N. , Bellai Louise G. , Koffi Judicaelle A. , Mathieu Tra-Bi I. , Ouattara Mamadou , Hürlimann Eveline , Coulibaly Jean T. , Diabaté Salia , N’Goran Eliézer K. , Utzinger Jürg
Published: January 2020

BackgroundPreventive chemotherapy with praziquantel is the cornerstone of schistosomiasis control. However, in some social-ecological settings, the prevalence and/or intensity of Schistosoma infection does not lower meaningfully despite multiple rounds of preventive chemotherapy, a phenomenon termed persistent hotspot (PHS). We assessed the characteristics of PHS in a Schistosoma mansoni-endemic area of Côte d’Ivoire.Methods: In October 2016, a cross-sectional parasitological survey was conducted in 14 schools in the western part of Côte d’Ivoire, one year after multiple rounds of preventive chemotherapy. In each school, 50 children aged 9-12 years were randomly selected and invited to submit two stool samples and one urine sample. Stool samples were subjected to triplicate Kato-Katz thick smears for S. mansoni diagnosis. Urine samples were examined by a filtration method for S. haematobium eggs. PHS was defined as failure to achieve a reduction in the prevalence and/or intensity of S. mansoni infection of at least 35% and 50%, respectively after multiple rounds of preventive chemotherapy targeting school-aged children. A questionnaire was administered in six schools to obtain data on demographic characteristics, including human-water contact behaviours, water, sanitation and hygiene and history of preventive chemotherapy. A malacological survey was conducted in December 2016.Results: The overall prevalence of S. mansoni and S. haematobium in the 14 surveyed schools was 9.5% and 2.6%, respectively. There were four PHS among six schools that underwent detailed investigation. The S. mansoni prevalence in the four PHS was 10.9% (95% confidence interval (CI): 6.4-15.5%), compared to 6.6% (95% CI: 1.4-11.8%) in the remaining two schools. The arithmetic mean of S. mansoni eggs per gram of stool (EPG) among infected children was 123.8 EPG in PHS and 18.7 EPG in the remaining two schools. A statistically significant difference between PHS and the other schools regarding praziquantel coverage was found with higher coverage rate observed in PHS (98.4% versus 89.0%, X2 = 3.7, p = 0.001). There was no significant difference with regard to access to clean water in the two groups of schools. Children bathing in open freshwater bodies were at higher odds of S. mansoni infection (odds ratio (OR) = 4.5, 95% CI: 1.6-12.6). A total of 76 human-water contact sites (53 in PHS and 23 in the other schools) were examined and 688 snails were collected, including 92 Biomphalaria pfeifferi, 25 Bulinus forskalii, 16 Bu. globosus and one Bu. truncatus.Conclusion: Children in PHS schools bathed more frequently in open freshwater bodies, and hence, they were potentially more exposed to S. mansoni. Our findings call for an integrated control approach, complementing preventive chemotherapy with behavioural change implementation in PHS settings.
Hypercharge quantisation and Fermat's last theorem
Authors: Lohitsiri Nakarin , Tong David
Published: January 2020

What values of the Standard Model hypercharges result in a
mathematically consistent quantum field theory? We show that the
constraints imposed by the lack of gauge anomalies can be recast as the
equation x^3 + y^3 = z^3x3+y3=z3.
If hypercharge is quantised, then xx,
yy
and zz
must be integers. The trivial (and only) solutions, with
x=0x=0
or y=0y=0,
reproduce the hypercharge assignments seen in Nature. This argument does
not rely on the mixed gauge-gravitational anomaly, which is
automatically vanishing if hypercharge is quantised and the gauge
anomalies vanish.
Near horizon dynamics of three dimensional black holes
Authors: Grumiller Daniel , Merbis Wout
Published: January 2020

We perform the Hamiltonian reduction of three dimensional Einstein
gravity with negative cosmological constant under constraints imposed by
near horizon boundary conditions. The theory reduces to a
Floreanini–Jackiw type scalar field theory on the horizon, where the
scalar zero modes capture the global black hole charges. The near
horizon Hamiltonian is a total derivative term, which explains the
softness of all oscillator modes of the scalar field. We find also a
(Korteweg–de Vries) hierarchy of modified boundary conditions that we
use to lift the degeneracy of the soft hair excitations on the
horizon.
Intronic miRNAs of Apoptosis Genes as Indicators of Cell Death
Authors: Makarova J.A. , Poloznikov A.A.
Published: January 2020

A method to assess the apoptosis level in cell models based on the analysis of the expression of micRNAs located in introns of apoptosis genes has been developed. Bioinformation analysis identified 536 genes associated with apoptosis; 30 of them contained 38 pre-microRNAs encoding 41 mature microRNAs. A significant change in the expression of hsa-miR-1244 and hsa-miR-4479 in response to apoptosis induction in the MCF-7 breast cancer cell line was revealed. A correlation was also found between the expression level of these miRNAs and the size of the primary tumor (process stage) in patients with breast cancer.

apoptosis, microRNA, MCF7, breast cancer

This work was supported by the Ministry of Education and Science of the Russian Federation (Project no. RFMEFI61618X0092).
Participation of Laminin α5-Chain in the Regulation of Colorectal Cancer Cell Differentiation
Authors: Raigorodskaya M.P. Raigorodskaya , Tsypina I.M. , Turchinovich A. , Zgoda V.G. , Nikulin S.V.
Published: January 2020

The effect of endogenous expression of the laminin α5 chain on the phenotype of colorectal cancer cells has been studied. For this purpose, the knockdown of LAMA5 gene coding for the α5 laminin chain in the HT29 colorectal adenocarcinoma cell line was carried out. The data on gene expression at both mRNA and protein levels indicate that the α5 laminin chain is involved in the regulation of cell differentiation. For example, a decrease in the expression of such markers of differentiation of the intestinal epithelium as SI, KRT20, ANXA13 and MUC13 was observed. In addition, the expression of the intestinal epithelial stem cell marker LRG5 and CD44 transmembrane protein was increased. Changing the phenotype of HT29 cells may be a result of the effect of the laminin α5 chain on the activity of the Wnt signaling pathway.

colorectal cancer, laminin, differentiation, dedifferentiation, intestinal epithelium stem cell marker, HT29, LAMA5, LRG5

The study was funded by the Russian Science Foundation (Project no. 17-14-01338).
Increase in the Production of Endo-1,4-β-Xylanase from Paenibacillus brasilensis in Pichia pastoris
Authors: Borshchevskaya L.N. , Gordeeva T.L. , Sineoky S.P.
Published: January 2020

A Pichia pastoris yeast strain producing endo-l,4-β-xylanase from Paenibacillus brasilensis with an activity of 54,400 U/mL after 140 h of fermentation in a laboratory fermenter has been obtained. A number of approaches were used to increase the level of the xylanase production in this strain: optimization of the target gene codon composition, multiple integration of the expression cassette into the recipient strain chromosome using the Cre-lox recombination system, and also improving the heterologous protein folding via the overexpression of the HAC1i gene from Pichia pastoris.

xylanase, xylan, Cre-lox system, HAC1p transcriptional activator, multicopy strain, Paenibacillus brasilensis, Pichia pastoris

The work was performed with the financial support of the Ministry of Education and Science of Russia (Unique Project Identifier RFMEFI60717X0180) using the Multipurpose Scientific Installation of «All-Russian Collection of Industrial Microorganisms» National Bio-Resource Center, NRC «Kurchatov Institute» - GosNIIgenetika.
Effect of Overexpression of the HAC1 Genes from Pichia pastoris and Saccharomyces cerevisiae on the Heterologous Phytase and Xylanase Production by P. pastoris
Authors: Borshchevskaya L.N. , Kalinina A.N. , Sineoky S.P. , Kashirskaya M.D.
Published: January 2020

Effect of overexpression of the HAC1 genes from Pichia pastoris and Saccharomyces cerevisiae on the production of heterologous enzymes, Escherichia coli phytase and Paenibacillus brasilensis xylanase, in P. pastoris cells has been studied. Codon composition of the phytase and xylanase encoding genes was optimized, and the genes were expressed in P. pastoris under the control of AOX1 promoter. The obtained multi-copy strains produced in vitro 927 U/mL phytase and 1,401 U/ml xylanase activity. Overexpression of the HAC1 gene from P. pastoris was shown to increase the phytase and xylanase production by 46% and 41%, respectively. Overexpression of HAC1 from S. cerevisiae increased the phytase production by 28% and xylanase by 20%. Data obtained could be helpful in the construction of industrial enzyme-producing strains based on P. pastoris.

phytase, xylanase, Нас1р transcription activator, UPR, Pichia pastoris, Saccharomyces cerevisiae

The work was carried out using Multipurpose Scientific Installation All-Russian Collection of Industrial Microorganisms National Bioresource Center, NRC «Kurchatov Institute» -GosNIIgenetika. The authors are grateful to A.V. Nikulin (Sintol LLC, Russia) for the assistance in the real-time PCR experiments.

The work was financially supported by the Ministry of Education and Science of the Russian Federation (Unique Identifiers of the Projects are RFMEFI57917X0145 and RFMEFI60717X0180).
HIF-1α Activation Reduces Expression of the microRNA hsa-miR-603 Host Gene KIAA1217 and Increases Expression of the Target CCND1 Gene in BeWo b30 Cells
Authors: Knyazeva E.A. , Nikulin S.V. , Khristichenko A.Yu. , Petrov V.A. , Turchinovich A. , Sergievich A.A.
Published: January 2020

The model of the placental barrier based on the human choriocarcinoma cell line BeWo b30 allows studying the effect of hypoxia on trophoblast cells. The effect of the oxyquinoline derivative inhibiting HIF-prolyl hydroxylases was studied on this model. Inhibition of these enzymes leads to an increase in the HIF-1α subunit in the cytoplasm, mimicking the cell response to hypoxia. Incubation of the cells with the drug at a concentration of 10 uM for 24 h did not affect the paracellular transport, but reduced the transport of glucose through the cell barrier. The transcriptome analysis after the exposure with oxyquinoline derivative revealed a decreased expression of the KIAA1217 gene and its intronic gene MIR603, which encodes microRNA hsa-miR-603. The expression of the target gene of this miRNA, CCND1 encoding cyclin D1, after oxyquinoline derivative exposition increased significantly, which may indicate a potential microRNA-mRNA regulatory mechanism in the response of trophoblast cells to hypoxia.

BeWo b30, placenta, hypoxia, oxyquinoline, barrier, microRNA, cyclin

The study was performed with the equipment of the «Postgenomic and Metabolomic Methods of Study in Molecular Biology» Common Use Center (BioClinicum Scientific and Technical Center).

The study was supported by the Ministry of Education and Science of the Russian Federation in the framework of the Federal Targeted Program for Research and Development in Priority Areas of Advancement of the Russian Scientific and Technological Complex for 2014-2020 (Project no. RFMEFI58817X0007).
Analysis of the Dynamics of the Electric Capacitance of a Cell Monolayer at the Late Stages of Caco-2 cell Differentiation
Authors: Nikulin S.V. , Petrov V.A. , Sakharov D.A.
Published: January 2020

The real-time monitoring of electric capacitance (impedance spectroscopy) allowed obtaining evidence that structures which look like intestinal villi can be formed during the cultivation under static conditions as well as during the cultivation in microfluidic chips. It was shown in this work via transcriptome analysis that the Hh signaling pathway is involved in the formation of villus-like structures in vitro, which was previously shown for their formation in vivo.

impedance spectroscopy, intestine, villi, electric capacitance, Hh

The study was funded by the Russian Science Foundation (Project 16-19-10597).
Properties and Biotechnological Application of mutant Derivatives of Mini-intein PRP8 from Penicillium chrysogenum with Improved Control of C-terminal Processing
Authors: Klebanov F.A. , Cheperegin S.E. , Kozlov D.G.
Published: January 2020

Mutant variants of mini-intein PRP8 from Penicillium chrysogenum (Int4b) with improved control of C-terminal processing were characterized. The presented variants can serve as a basis for self-removed polypeptide tags capable of carrying an affine label and allowing to optimize the process of obtaining target proteins and peptides in E. coli cells. They allow to synthesize target molecules in the composition of soluble and insoluble hybrid proteins (fusions), provide their afnne purification, autocatalytic processing and obtaining mature target products. The presented variants have a number of features in comparison with the known prototypes. In particular the mutant mini-intein Int4bPRO, containing the L93P mutation, has temperature-dependent properties. At cultivation temperature below 30 °C it allows the production of target molecules as part of soluble fusions, but after increasing of cultivation temperature to 37 °C it directs the most of synthesized fusions into insoluble intracellular aggregates. The transition of Int4bPRO into insoluble form is accompanied by complete inactivation of C-terminal processing. Further application of standard protein denaturation-renaturation procedures enable efficiently reactivate Int4bPRO and to carry out processing of its fusions in vitro. Two other variants, Int4b56 and Int4b36, containing a point mutation T62N or combination of mutations D144N and L146T respectively, have a reduced rate of C-terminal processing. Their use in E. coli cells allows to optimize the biosynthesis of biologically active target proteins and peptides in the composition of soluble fusions, suitable for afnne purification and subsequent intein-dependent processing without the use of protein denaturation-renaturation procedures.

intein, fusion, processing, processing rate, gelonin

The work was supported within the framework of the State Assignment no. 595-00003-19 PR.
Seasonal changes in the phylloplane of genus Gnetum (Gnetaceae) representatives in greenhouse conditions
Authors: Bogdanova Ianina , Pautov Anatoly , Zelenskaya Marina , Krylova Elena , Vlasov Dmitry
Published: January 2020

The leaf surface, or phylloplane, is inhabited by various microorganisms. Micromycetes are typical organisms of the phylloplane that are able to exert negative effects on plants. Seventeen species of micromycetes were indicated in the phylloplanes of G. gnemon and G. montanum. Micromycetes form biofilms on the surface of the upper epidermis. In the lower epidermis, they mainly colonize cork warts and destroy their cells. Collapsing cells and the micromycetes are isolated from the living tissues of leaves by layers of densely arranged cells. During changes from season to season, the number of disappearing micromycete species in the upper epidermis is approximately equal to the number of appearing new species. The total number of micromycete species in the phylloplane of the lower epidermis is reduced in winter. Structural organization, biodiversity, seasonal changes in the phylloplane and the influence of its micromycetes on leaf cells differ in the upper and lower epidermis of Gnetum leaves.