bluuebunny/crossref_metadata_2025 huggingface dataset:
When piloting health services interventions, what predicts real world behaviours? A systematic concept mapping review
Authors: Hayes Tavis , Hudek Natasha , Graham Ian D. , Coyle Doug , Brehaut Jamie C.
Published: April 2020

Background

Modeling studies to inform the design of complex health services interventions often involves elements that differ from the intervention’s ultimate real-world use. These “hypothetical” elements include pilot participants, materials, and settings. Understanding the conditions under which studies with “hypothetical” elements can yield valid results would greatly help advance health services research. Our objectives are:1) to conduct a systematic review of the literature to identify factors affecting the relationship between hypothetical decisions and real-world behaviours, and 2) to summarise and organize these factors into a preliminary framework.

Methods

We conducted an electronic database search using PsycINFO and Medline on November 30th, 2015, updated March 7th, 2019. We also conducted a supplemental snowball search on December 9th 2015 and a reverse citation search using Scopus and Web of Science. Studies were eligible to be included in this review if they clearly addressed the consistency between some type of hypothetical decision and a corresponding real decision or behaviour. Two reviewers extracted data using a standardized data collection form developed through an iterative consensus-based process. We extracted basic study information and data about each study’s research area, design, and research question. Quotations from the articles were extracted and summarized into standardized factor statements.

Results

Of the 2444 articles that were screened, 68 articles were included in the review. The articles identified 27 factors that we grouped into 4 categories: decision maker factors, cognitive factors, task factors, and matching factors.

Conclusions

We have summarized a large number of factors that may be relevant when considering whether hypothetical health services pilot work can be expected to yield results that are consistent with real-world behaviours. Our descriptive framework can serve as the basis for organizing future work exploring which factors are most relevant when seeking to develop complex health services interventions.
International tuberculosis contact-tracing notifications in Germany: analysis of national data from 2010 to 2018 and implications for efficiency
Authors: Glasauer Saskia , Kröger Stefan , Haas Walter , Perumal Nita
Published: April 2020

Background

International contact-tracing (CT) following exposure during long-distance air travel is resource-intensive, whereas evidence for risk of tuberculosis (TB) transmission during international travel is weak. In this study, we systematically analyzed the information from international requests for CT received at the national level in Germany in order to evaluate the continued utility of the current approach and to identify areas for improvement.

Methods

An anonymized archive of international CT notifications received by the Robert Koch Institute between 2010 and 2018 was searched for key parameters for data collection. A total of 31 parameters, such as characteristics of TB patients and their identified contacts, were extracted from each CT notification and collated into a dataset. Descriptive data analysis and trend analyses were performed to identify key characteristics of CT notifications, patients, and contacts over the years.

Results

192 CT notifications, each corresponding to a single TB index case, were included in the study, increasing from 12 in 2010 to 41 in 2018. The majority of notifications (N = 130, 67.7%) concerned international air travel, followed by private contact (N = 39, 20.3%) and work exposure (N = 16, 8.3%). 159 (82.8%) patients had sputum smear results available, of which 147 (92.5%) were positive. Of 119 (62.0%) patients with drug susceptibility testing results, most (N = 92, 77.3%) had pan-sensitive TB, followed by 15 (12.6%) with multi-drug resistant TB. 115 (59.9%) patients had information on infectiousness, of whom 99 (86.1%) were considered infectious during the exposure period. 7 (5.3%) patients travelled on long-distance flights despite a prior diagnosis of active TB. Of the 771 contact persons, 34 (4.4%) could not be reached for CT measures due to lack of contact information.

Conclusion

The high variability in completeness of information contained within the international CT requests emphasizes the need for international standards for reporting of CT information. With the large proportion of TB patients reported to have travelled while being infectious in our study, we feel that raising awareness among patients and health professionals to detect TB early and prevent international long-distance travel during the infectious disease phase should be a cornerstone strategy to safeguard against possible transmission during international travel.
Cortical unlike trabecular bone loss is not associated with vascular calcification progression in CKD patients
Authors: Costa Larissa R. , Carvalho Aluizio B. , Bittencourt Amandha L. , Rochitte Carlos E. , Canziani Maria Eugênia F.
Published: April 2020

Background

Vascular calcification progression has been associated with the loss of trabecular bone in chronic kidney disease (CKD) patients. There are few data evaluating the relationship between cortical bone loss and vascular calcification in this population. The aim of this study was to prospectively evaluate the association between changes in cortical bone density and coronary artery calcification (CAC) progression in non-dialyzed CKD patients.

Methods

Changes of cortical and trabecular bone, and changes of calcium score, were analyzed using vertebral tomographic images from a prospective study. Automatic delineation of the cortical bone layer was performed by Image J software, and trabecular bone was determined by selecting a region of interest using Vitrea 2® software. Cortical and trabecular bone density (BD) were expressed in Hounsfield Units (HU), and coronary artery calcium score in Agatston Units (AU).

Results

Seventy asymptomatic patients [57.8 ± 10.2 years, 63% males, 20% diabetic, estimated glomerular filtration rate (eGFR) = 37.3 (24.8–51.3) mL/min/1.73m2] were followed for 24 months. The mean cortical and trabecular BD did not change over time. While 49 patients lost either bone, 29 (41%) patients lost cortical [− 4.4%/year (ranging from − 7.15 to − 0.5)] and 39 (56%) lost trabecular bone [− 3.15%/year (− 13.7 to − 0.25)]. There was no association between cortical and trabecular BD changes (p = 0.12). CAC was observed in 33 (46%) patients at baseline, and 30 (91%) of them showed CAC progression. While an inverse correlation between trabecular bone and calcium score changes was observed (p = 0.001), there was no correlation between cortical bone and calcium score changes (p = 0.34).

Conclusion

CKD patients experience either cortical or trabecular bone loss over time, but these changes do not take place simultaneously in all patients. Cortical, unlike trabecular bone loss, is not associated with vascular calcification progression in these patients.
The impact of hyperglycemia on urinary albumin excretion in recent onset diabetes mellitus type II
Authors: Nikolaidou Barbara , Gkaliagkousi Eugenia , Anyfanti Panagiota , Gavriilaki Eleni , Lazaridis Antonios , Triantafyllou Areti , Zografou Ioanna , Douma Stella
Published: April 2020

Background

Increased urinary albumin excretion (UAE) in diabetes is a sensitive marker of microvascular injury and a reliable predictor of cardiovascular outcomes. Hypertension-induced hemodynamic pressure load, diabetes-related metabolic processes and large artery stiffening have all been implicated in the development of microalbuminuria. We investigated whether hyperglycemia per se, or rather increased blood pressure (BP) and macrovascular dysfunction, is a stronger predictor of UAE at the earliest stages of diabetes.

Methods

Consecutive newly diagnosed patients with diabetes type 2, who were normoglycemic within a year’s time prior to diagnosis, were enrolled. UAE was estimated in 24-h urine samples. Both office and 24-h ambulatory BP was recorded. Arterial stiffness was evaluated by measurement of carotid-femoral pulse wave velocity (PWV) with applanation tonometry.

Results

Among 71 newly diagnosed patients with median diabetes duration of just 1 month, 15.5% presented microalbuminuria. UAE did not differ between hypertensive and normotensive diabetics; however, newly diagnosed patients for both hypertension and diabetes exhibited significantly higher levels of UAE, compared to diabetic patients with long-standing hypertension. UAE strongly and significantly correlated with office systolic BP, HbA1c, PWV and estimated glomerular filtration rate. However, in the multivariate analysis adjusting for these factors, only HbA1c was independently associated with UAE (beta = 0.278, p = 0.049).

Conclusions

Hyperglycemic state emerges as a powerful predictor of increased UAE even at the earliest stages of diabetes. The relative contribution of hypertension and macrovascular dysfunction to the development of microalbuminuria seems to be obscured by hyperglycemia, even in patients whose diabetes onset does not exceed a few months’ time.
Beta-glucans in advanced CKD: role in endotoxaemia and inflammation
Authors: Wong Jonathan , Zhang Yonglong , Swift Oscar , Finkelman Malcolm , Patidar Ashish , Ramanarayanan Sivaramakrishnan , Vilar Enric , Farrington Ken
Published: April 2020

Background/aims

(1–3)-β-D glucans (BG) are cellular components of yeasts and fungi. Elevated blood levels may be an adjunct in diagnosing invasive fungal infection, though can be high in dialysis patients without fungaemia. BG can also induce false positive signals in endotoxin detection assays (Limulus Amoebocyte Lysate [LAL] assay). We explored the relationship between BG levels, renal impairment, endotoxaemia and inflammation.

Methods

We measured serum BG levels, markers of inflammation and blood endotoxin levels in 20 controls, 20 with stages 1–3 chronic kidney disease (CKD), 20 with stages 4–5 CKD, 15 on peritoneal dialysis (PD) and 60 on haemodialysis (HD). Another 30 patients were studied before and after HD initiation.

Results

BG levels increased with advancing CKD, being highest in HD patients, 22% of whom had elevated levels (> 80 pg/ml). Levels increased significantly following HD initiation. Levels also correlated positively with CRP, TNFα, IL-6 levels, independently of CKD stage. Blood endotoxin was detectable by LAL assays in 10–53% of the CKD cohort, being most prevalent in the HD group, and correlating positively with BG levels. Adding BG blocking agent to the assay reduced endotoxin detection confining it to only 5% of HD patients. Levels of inflammatory markers were higher in those with detectable endotoxin - whether false- or true positives.

Conclusion

BG levels increased with decreasing renal function, being highest in dialysis patients. High BG levels were associated with false positive blood endotoxin signals, and with markers of inflammation, independently of CKD stage. The cause for high BG levels is unknown but could reflect increased gut permeability and altered mononuclear phagocytic system function.
Genetic analysis of spinal dysraphism with a hamartomatous growth (appendix) of the spinal cord: a case series
Authors: Bartels Ronald H. M. A. , Grotenhuis J. Andre , Stegmann Alexander P. A. , Brunner Han
Published: April 2020

Background

Spinal dysraphism with a hamartomatous growth (appendix) of the spinal cord is better known as herniated spinal cord. There are many arguments in favour of considering it a developmental defect. From this point of view, it is a type of neural tube disorder. Neural tube disorders can be caused by multiple factors, including a genetic factor. A common genetic defect in patients with a spinal dysraphism with a hamartomatous growth of the spinal cord is sought for.

Case presentation

In two patients with a symptomatic lesion and referred to an academic hospital a genetic analysis was performed after informed consent. Whole-exome analysis was performed.

: Whole-exome analysis did not result in identification of a clinically relevant genetic variant.

Conclusions

This the first study to investigate the genetic contribution to spinal dysraphism with a hamartomatous growth (appendix) of the spinal cord. We could not establish a genetic cause for this entity. This conclusion cannot be definitive due to the small sample size. However, the incidental occurrence, the lack of reports of inheritance of this disorder and the absence of contribution to syndromal disorders favours a defect of normal development of the spinal cord.
Current heterosexual marriage is associated with significantly decreased levels of anxiety symptoms among Chinese men who have sex with men
Authors: Yang Zuosen , Li Shuang , Zhang Rui , Na Jun , Li Yanxia , Mu Huijuan , Yu Liya , Liu Li , Sun Wei , Pan Guowei , Yan Lingjun
Published: April 2020

Background

The high heterosexual marriage rate could be a ‘double-edge’ sword for the emotional health of Chinese men who have sex with men (MSM). The aim of this study was to determine if current marriage and breakdown of marriage (divorce) have different effects on the mental health of Chinese MSM.

Methods

Eight hundred seven MSM were recruited using respondent-driven sampling from four cities in northeastern China. Gay-related stressful events (GRSE) were measured using the Gay Related Stressful Life Events Scale; social support was measured by the Social Support Rating Scale (SSRS); and depressive and anxiety symptoms were assessed using the Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS), respectively.

Results

Of the study participants, 13.4% were married to women and 4.5% were divorced. The rates of marriage or divorce were 35.3 and 75.8% for participants 30–39 and > 40 years of age, respectively. The current married MSM had the highest SDS (50.0 ± 10.9) and SSRS (35.8 ± 8.6) levels, but the lowest SAS (38.7 ± 12.1) levels. Divorced MSM had the highest SAS (44.4 ± 9.6) and lowest SSRS (30.8 ± 8.1) levels. Age, GESE number, and HIV infection were predictors for SDS and SAS, and current marriage was associated with significantly decreased level of SAS (β = − 0.136, P = 0.001) based on multiple linear analysis.

Conclusions

Current marriage is associated with significantly decreased levels of anxiety symptoms among Chinese MSM. More studies are needed to understand the mechanisms underlying the effects of different marriage status on the emotional distress of Chinese MSM.
Occupational exposure to HIV among healthcare workers in PMTCT sites in Port Harcourt, Nigeria
Authors: Akpuh Ndubuisi , Ajayi IkeOluwapo , Adebowale Ayo , Idris Suleiman Hadejia , Nguku Patrick , Dalhat Mahmood , Adedire Elizabeth
Published: April 2020

Background

Rivers State is among the states with high HIV prevalence in Nigeria. Occupational exposure to HIV through blood or body fluids of HIV/AIDS patients is a recognised risk factor of HIV infections among healthcare workers. We identified the determinants of occupational exposures to HIV among healthcare workers in Prevention of Maternal to Child Transmission (PMTCT) sites within Port Harcourt metropolis in Rivers State.

Methods

A descriptive cross-sectional study was conducted and multi-stage sampling technique was used to select 341 healthcare providers from 22 public and 22 private health facilities in PMTCT sites in Port Harcourt metropolis. The data collected were analysed using descriptive statistics, Chi-square and logistic regression models (p-value = 0.05).

Results

Respondents’ mean age was 35.9 ± SD8.4 years, 270 (80.1%) and 171(50.7%) were females, and from public health facilities respectively. Prevalence of occupational exposure of healthcare workers to HIV in the past 12 months was 153 (45.0%), and 96 (63.3%) experienced such exposure more than once. Contacts with potentially infectious body fluid accounted for the largest proportion 51 (33.3%); followed by needle stick prick 49 (32.6%). About 189 (56.1%) had safety information at their disposal and this serves as a reminder on safety precautions. The likelihood of occupational exposure was significantly higher among doctors (AOR = 2.22, 95% C.I = 1.16–4.25,) but lower among environmental health workers (AOR = 0.10, 95% C.I = 0.02–0.46,) than nurses/midwives when other factors were included in the model.

Conclusion

Occupational exposure to blood and body fluids remains a frequent occurrence among healthcare workers; highest among doctors in PMTCT sites in the study area. Provision of protective safety materials, training and enforcement of adherence to universal precaution strategies are highly recommended.
Foot health among the Roma population of southern Spain according to the foot health status questionnaire
Authors: Coheña-Jiménez Manuel , Chicharro-Luna Esther , Algaba-Del-Castillo José , Páez-Tudela Amanda
Published: April 2020

Background

Foot health of the Roma population is a challenge for the health professionals where this minority is significant, as is the case in Spain. At present, little is known about foot health of the Roma population and their knowledge would promote the training of these professionals at the community level. Foot pain is common and a reason for consulting podiatry services. The purpose of this study was to determine foot health among the Roma population according to the Foot Health Status Questionnaire.

Method

An observational, cross-sectional and quantitative study conducted at the Roma population living in Spain in 2018. Self-reported data and the Foot Health Status Questionnaire were recorded. Examining the general health and foot health (foot pain, foot function, footwear and general health) and general (general health, social capacity, physical activity and vigour). This questionnaire is recommended as a valid and reliable patient-reported outcome. The obtained scores were compared.

Results

A sample made up of 624 men and women from the Roma population took part in this study. 45% were Roma men and 55% Roma women. In the first section of the FHSQ, a lower score of values was recorded in the footwear domain (62.5) and in the general foot health domain (60). Gypsy women obtained lower scores in all the domains. In the second section, lower scores were obtained in the vigour (56) domain and in the general health (60) domain. A large effect size (r-Rosenthal) was found by gender in the footwear domain (0.334) and in the vigour domain (0.195). Roma women showed higher values in cardiac disorders, serious illnesses, doctor visits and foot problems. 67.8% reported that they had never been assisted by a podiatrist.

Conclusions

The studied Roma population has foot health problems, and these are more pronounced among women. They show lower values in the footwear and vigour domains. More professional training is required for health workers in this field to avoid cultural diversity stereotypes.
The influence of adipose-derived stromal vascular fraction cells on the treatment of knee osteoarthritis
Authors: Tsubosaka Masanori , Matsumoto Tomoyuki , Sobajima Satoshi , Matsushita Takehiko , Iwaguro Hideki , Kuroda Ryosuke
Published: April 2020

Background

Adipose-derived stromal vascular fraction (SVF) cells are a mixed cell population that includes cells with multilineage potential, similar to bone marrow-derived mesenchymal stem cells. Our purpose is to investigate the influence of SVF cells in patients with knee osteoarthritis (OA) and the short-term treatment effects.

Methods

Fifty-seven patients were enrolled and treated with intra-articular injection of 2.5 × 107 SVF cells into the knee joint between September 2017 and March 2018. All patients were followed up for 12 months or longer. Mean age at treatment and follow-up period were 69.4 ± 6.9 years and 13.7 ± 2.0 months, respectively. The mean preoperative hip-knee-ankle angle was 6.7 ± 3.6°. SVF cells were prepared using the Celution®800/CRS system from the patients’ abdominal or breech subcutaneous fat. The mean SVF cell viability was 90.6 ± 2.7%. Clinical evaluations were performed for range of motion, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and the Knee injury and Osteoarthritis Score (KOOS). Imaging evaluations, which included the hip-knee-ankle angle assessed via radiography, and T2 mapping value using a 1.5-T magnetic resonance imaging unit were also assessed. Both clinical and imaging evaluations were performed preoperatively, 1, 3, 6, and 12 months postoperatively, and compared among all timepoints (p < 0.05).

Results

Knee extension angle at 6 and 12 months postoperatively was significantly better than the preoperative angle. Total WOMAC, VAS, and KOOS scores at 1, 3, 6 and 12 months postoperatively were significantly better than preoperative scores. There was no significant difference in hip-knee-ankle angle among the five time periods. T2 mapping values of lateral femur and tibia were significantly higher 12 months postoperatively than preoperatively.

Conclusions

The short-term clinical effects of intra-articular SVF cell injection on knee OA were excellent. Intra-articular SVF cell injection is a novel and innovative approach for treating patients with knee OA.
Minimally invasive versus conventional fixation of tracer in robot-assisted pedicle screw insertion surgery: a randomized control trial
Authors: Yongqi Li , Dehua Zhang , Hongzi Wu , Ke Zhang , Rui Yang , Zhou Fang , Shaobo Wang , Yi Liao
Published: April 2020

Background

This study evaluated the minimal invasiveness, safety, and accuracy of robot-assisted pedicle screw placement procedure using a modified tracer fixation device.

Methods

Patients were randomly assigned to conventional fixation group (25 patients) and modified fixation group (27 patients).

Results

No baseline statistical difference was observed between the groups (P > 0.05). The length of unnecessary incision, amount of bleeding, and fixation duration for tracer fixation respectively were 6.08 ± 1.02 mm, 1.46 ± 0.84 ml, and 1.56 ± 0.32 min in the modified fixation group and 40.28 ± 8.52 mm, 12.02 ± 2.24 ml, and 5.08 ± 1.06 min in the conventional group. The difference between both groups was significant (P < 0.05). However, no significant difference between the two groups was observed in terms of the accuracy of pedicle screw placement (P > 0.05).

Conclusions

The modified minimally invasive procedure for tracer fixation results in minimal trauma and is simple, reliable, and highly safe. Additionally, the procedure does not compromise the accuracy of pedicle screw placement. Thus, it has great clinical applicable value.

Trial registration

Chinese Clinical Trial Registry: Registration number, ChiCTR1800016680; Registration Date, 15/06/2018.
Knowledge and practices regarding tuberculosis infection control among nurses in Ibadan, south-west Nigeria: a cross-sectional study
Authors: Akande Patrick Aboh
Published: April 2020

Background

Nurses are particularly vulnerable to nosocomial tuberculosis (TB) infection because, being in the frontline of healthcare provision, they are frequently exposed to patients with infectious TB disease. Although cost-effective measures are available for TB infection control (TBIC), they are often poorly implemented. Knowledge of TBIC is known to positively influence the practice of the measures. There is, however, paucity of data on the knowledge and practices regarding TBIC among nurses in Nigeria. This study was aimed at determining the levels of TBIC-related knowledge and practices of nurses in Ibadan, and their associated socio-demographic factors.

Methods

This cross-sectional study utilized a self-administered questionnaire to collect data from 200 nurses in two secondary health facilities, in May 2014. The mean knowledge and practice scores of the nurses were determined and logistic regression was utilized to explore the association between the scores and socio-demographic characteristics.

Results

The respondents had mean knowledge and practice scores of 68.2 and 79.9% respectively. Using cut-off points of 80 and 100% for good knowledge and practice scores respectively, small proportions of the nurses had good scores – knowledge (10.5%) and practice (6%). Knowledge was not significantly associated with the socio-demographic characteristics of the nurses. Work experience was the only factor that was significantly associated with practices, with the more experienced nurses (> 18 years of work experience) having lower odds of obtaining good practice scores (OR 0.25, 95% CI 0.06–0.94). There was also no significant association between knowledge and practice scores (the nurses were yet to be trained on the newly-introduced TBIC package at the time of the study).

Conclusions

The study revealed that small proportions of the nurses had good knowledge and practice scores. Its findings will be useful for the designing of interventions to improve TBIC among nurses and other healthcare workers, and to benchmark evaluation of the interventions. It is recommended that nurses should be trained on TBIC to equip them with necessary knowledge and skills. This, together with appropriate policy directives, and adequate monitoring and supervision will contribute to optimal implementation of TB preventive measures.
A comparison of psychometric properties of two common measures of caregiving burden: the family burden interview schedule (FBIS-24) and the Zarit caregiver burden interview (ZBI-22)
Authors: Yu Yu , Liu Zi-wei , Li Tong-xin , Zhou Wei , Xi Shi-jun , Xiao Shui-yuan , Tebes Jacob Kraemer
Published: April 2020

Purpose

The Family Burden Interview Schedule (FBIS-24) and the Zarit Caregiver Burden Interview (ZBI-22) are among the most widely used measures for assessing caregiving burden, but their psychometric performances have not been compared in the same study of caregivers of people living with schizophrenia (PLS). This is important because the measures assess overlapping constructs- the FBIS-24 assesses objective burden (e.g., completion of manual tasks) and the ZBI-22 assesses subjective burden (e.g., perceived distress, stigma). This study seeks to fill this gap by comparing the reliability and validity of the FBIS-24 and the ZBI-22 in a Chinese community sample of caregivers of PLS.

Methods

A Cross-sectional stud was conducted in a community-based mental health service program in Central South part of China. A total of 327 primary family caregivers of PLS completed face-to-face interviews of the FBIS-24, the ZBI-22, the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder Scale (GAD-7), and the Family Adaptation, Partnership, Growth, Affection and Resolve Index scale (APGAR), and PLS were assessed using the Global Assessment of Function scale (GAF).

Results

Our findings show that both the FBIS-24 and ZBI-22 have comparable psychometric performance in terms of the internal consistency, convergent validity and known group’s validity.

Conclusion

Both the FBIS-24 and the ZBI-22 are psychometrically sound measures of caregiving burden but the choice of which measure to use will depend on the research question.
MicroRNA-153 impairs presynaptic plasticity by blocking vesicle release following chronic brain hypoperfusion
Authors: Yan Mei-Ling , Zhang Shuai , Zhao Hong-Mei , Xia Sheng-Nan , Jin Zhuo , Xu Yi , Yang Lin , Qu Yang , Huang Si-Yu , Duan Ming-Jing , Mao Meng , An Xiao-Bin , Mishra Chandan , Zhang Xin-Yu , Sun Li-Hua , Ai Jing
Published: April 2020

Background

Chronic brain hypoperfusion (CBH) is closely related to Alzheimer’s disease (AD) and vascular dementia (VaD). Meanwhile, synaptic pathology plays a prominent role in the initial stage of AD and VaD. However, whether and how CBH impairs presynaptic plasticity is currently unclear.

Methods

In the present study, we performed a battery of techniques, including primary neuronal culture, patch clamp, stereotaxic injection of the lentiviral vectors, morris water maze (MWM), dual luciferase reporter assay, FM1–43 fluorescence dye evaluation, qRT-PCR and western blot, to investigate the regulatory effect of miR-153 on hippocampal synaptic vesicle release both in vivo and in vitro. The CBH rat model was generated by bilateral common carotid artery ligation (2VO).

Results

Compared to sham rats, 2VO rats presented decreased field excitatory postsynaptic potential (fEPSP) amplitude and increased paired-pulse ratios (PPRs) in the CA3-CA1 pathway, as well as significantly decreased expression of multiple vesicle fusion-related proteins, including SNAP-25, VAMP-2, syntaxin-1A and synaptotagmin-1, in the hippocampi. The levels of microRNA-153 (miR-153) were upregulated in the hippocampi of rats following 2VO surgery, and in the plasma of dementia patients. The expression of the vesicle fusion-related proteins affected by 2VO was inhibited by miR-153, elevated by miR-153 inhibition, and unchanged by binding-site mutation or miR masks. FM1–43 fluorescence images showed that miR-153 blunted vesicle exocytosis, but this effect was prevented by either 2′-O-methyl antisense oligoribonucleotides to miR-153 (AMO-153) and miR-masking of the miR-153 binding site in the 3′ untranslated region (3’UTR) of the Snap25, Vamp2, Stx1a and Syt1 genes. Overexpression of miR-153 by lentiviral vector-mediated miR-153 mimics (lenti-pre-miR-153) decreased the fEPSP amplitude and elevated the PPR in the rat hippocampus, whereas overexpression of the antisense molecule (lenti-AMO-153) reversed these changes triggered by 2VO. Furthermore, lenti-AMO-153 attenuated the cognitive decline of 2VO rats.

Conclusions

Overexpression of miR-153 controls CBH-induced presynaptic vesicle release impairment by posttranscriptionally regulating the expression of four vesicle release-related proteins by targeting the 3’UTRs of the Stx1a, Snap25, Vamp2 and Syt1 genes. These findings identify a novel mechanism of presynaptic plasticity impairment during CBH, which may be a new drug target for prevention or treatment of AD and VaD.

Graphical abstract
The NLRP3 inflammasome in traumatic brain injury: potential as a biomarker and therapeutic target
Authors: O’Brien William T. , Pham Louise , Symons Georgia F. , Monif Mastura , Shultz Sandy R. , McDonald Stuart J.
Published: April 2020

There is a great clinical need to identify the underlying mechanisms, as well as related biomarkers, and treatment targets, for traumatic brain injury (TBI). Neuroinflammation is a central pathophysiological feature of TBI. NLRP3 inflammasome activity is a necessary component of the innate immune response to tissue damage, and dysregulated inflammasome activity has been implicated in a number of neurological conditions. This paper introduces the NLRP3 inflammasome and its implication in the pathogenesis of neuroinflammatory-related conditions, with a particular focus on TBI. Although its role in TBI has only recently been identified, findings suggest that priming and activation of the NLRP3 inflammasome are upregulated following TBI. Moreover, recent studies utilizing specific NLRP3 inhibitors have provided further evidence that this inflammasome is a major driver of neuroinflammation and neurobehavioral disturbances following TBI. In addition, there is emerging evidence that circulating inflammasome-associated proteins may have utility as diagnostic biomarkers of neuroinflammatory conditions, including TBI. Finally, novel and promising areas of research will be highlighted, including the potential involvement of the NLRP3 inflammasome in mild TBI, how factors such as biological sex may affect NLRP3 activity in TBI, and the use of emerging biomarker platforms. Taken together, this review highlights the exciting potential of the NLRP3 inflammasome as a target for treatments and biomarkers that may ultimately be used to improve TBI management.
Deubiquitinating enzymes (DUBs): DoUBle-edged swords in CNS autoimmunity
Authors: Ruan Jing , Schlüter Dirk , Wang Xu
Published: April 2020

Multiple sclerosis (MS) is the most common autoimmune disease of the CNS. The etiology of MS is still unclear but it is widely recognized that both genetic and environmental factors contribute to its pathogenesis. Immune signaling and responses are critically regulated by ubiquitination, a posttranslational modification that is promoted by ubiquitinating enzymes and inhibited by deubiquitinating enzymes (DUBs). Genome-wide association studies (GWASs) identified that polymorphisms in or in the vicinity of two human DUB genes TNFAIP3 and USP18 were associated with MS susceptibility. Studies with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, have provided biological rationale for the correlation between these DUBs and MS. Additional studies have shown that other DUBs are also involved in EAE by controlling distinct cell populations. Therefore, DUBs are emerging as crucial regulators of MS/EAE and might become potential therapeutic targets for the clinical treatment of MS.
Astragaloside IV inhibits astrocyte senescence: implication in Parkinson’s disease
Authors: Xia Mei-Ling , Xie Xia-Hong , Ding Jian-Hua , Du Ren-Hong , Hu Gang
Published: April 2020

Background

Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson’s disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined.

Methods

Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP+)-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers.

Results

We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP+-induced premature senescence, evidenced by decreased senescence-associated β-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence.

Conclusions

Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.
Perceived barriers to randomised controlled trials in breast reconstruction: obstacle to trial initiation or opportunity to resolve? A qualitative study
Authors:   on behalf of the iBRA Steering Group, Davies Gareth , Mills Nicola , Holcombe Chris , Potter Shelley
Published: April 2020

Background

Implant-based breast reconstruction (IBBR) is the most commonly performed breast reconstruction technique worldwide but the technique is evolving rapidly. High-quality evidence is needed to support practice. Randomised controlled trials (RCTs) provide the best evidence but can be challenging to conduct.

iBRA is a four-phased study which aimed to inform the feasibility, design and conduct of an RCT in IBBR. In phase 3, the randomisation acceptability study, an electronic survey and qualitative interviews were conducted to explore professionals’ perceptions of future trials in IBBR. Findings from the interviews are presented here.

Methods

Semi-structured qualitative interviews were undertaken with a purposive sample of 31 health professionals (HPs) who completed the survey to explore their attitudes to the feasibility of potential RCTs in more detail. All interviews were transcribed verbatim and data were analysed thematically using constant comparative techniques. Sampling, data collection and analysis were undertaken iteratively and concurrently until data saturation was achieved.

Results

Almost all HPs acknowledged the need for better evidence to support the practice of IBBR and most identified RCTs as generating the highest-quality evidence. Despite highlighting potential challenges, most participants supported the need for an RCT in IBBR. A minority, however, were strongly opposed to a future trial. The opposition and challenges identified centred around three key themes; (i) limited understanding of pragmatic study design and the value of randomisation in minimising bias; (ii) clinician and patient equipoise and (iii) aspects of surgical culture and training that were not supportive of RCTs.

Conclusion

There is a need for well-designed, large-scale RCTs to support the current practice of IBBR but barriers to their acceptability are evident. The perceived barriers to RCTs in breast reconstruction identified in this study are not insurmountable and have previously been overcome in other similar surgical trials. This may represent an opportunity, not only to establish the evidence base for IBBR, but also to improve engagement in RCTs in breast surgery in general to ultimately improve outcomes for patients.

Trial registration

International Standard Randomised Controlled Trial Number ISRCTN37664281.
Genetic uniformity, geographical spread and anthropogenic habitat modifications of lymnaeid vectors found in a One Health initiative in the highest human fascioliasis hyperendemic of the Bolivian Altiplano
Authors: Bargues M. Dolores , Artigas Patricio , Angles Rene , Osca David , Duran Pamela , Buchon Paola , Gonzales-Pomar R. Karina , Pinto-Mendieta Julio , Mas-Coma Santiago
Published: April 2020

Background

Fascioliasis is a snail-borne zoonotic trematodiasis emerging due to climate changes, anthropogenic environment modifications, and livestock movements. Many areas whereFasciola hepaticais endemic in humans have been described in Latin America altitude areas. Highest prevalences and intensities were reported from four provinces of the northern Bolivian Altiplano, where preventive chemotherapy is ongoing. New strategies are now incorporated to decrease infection/re-infection risk, assessment of human infection sources to enable efficient prevention measures, and additionally a One Health initiative in a selected zone. Subsequent extension of these pilot interventions to the remaining Altiplano is key.

Methods

To verify reproducibility throughout, 133 specimens from 25 lymnaeid populations representative of the whole Altiplano, and 11 used for population dynamics studies, were analyzed by rDNA ITS2 and ITS1 and mtDNAcox1 and16Ssequencing to assess their classification, variability and geographical spread.

Results

Lymnaeid populations proved to belong to a monomorphic group,Galba truncatula. Only a singlecox1 mutation was found in a local population. Twocox1 haplotypes were new. Comparisons of transmission foci data from the 1990’s with those of 2018 demonstrated an endemic area expansion. Altitudinal, northward and southward expansions suggest movements of livestock transportingG. truncatulasnails, with increasing temperatures transforming previously unsuitable habitats into suitable transmission areas. Transmission foci appear to be stable when compared to past field observations, except for those modified by human activities, including construction of new roads or control measures undertaken in relation to fascioliasis.

Conclusions

For a One Health initiative, the control of only oneFasciolaspecies and snail vector species simplifies efforts because of the lower transmission complexity. Vector monomorphism suggests uniformity of vector population responses after control measure implementation. Hyperendemic area outer boundary instability suggests a climate change impact. All populations outside previously known boundaries were close to villages, human dwellings and/or schools, and should therefore be considered during disease control planning. The remarkable southward expansion implies that a fifth province, Aroma, should now be included within preventive chemotherapy programmes. This study highlights the need for lymnaeid molecular identification, transmission foci stability monitoring, and potential vector spread assessment.
Leu124Serfs*26, a novel AGPAT2 mutation in congenital generalized lipodystrophy with early cardiovascular complications
Authors: Montenegro Junior Renan Magalhães , Lima Grayce Ellen da Cruz Paiva , Fernandes Virgínia Oliveira , Montenegro Ana Paula Dias Rangel , Ponte Clarisse Mourão Melo , Martins Lívia Vasconcelos , Pinheiro Daniel Pascoalino , de Moraes Maria Elisabete Amaral , de Moraes Filho Manoel Odorico , d’Alva Catarina Brasil
Published: April 2020

Background

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by the near-total loss of subcutaneous adipose tissue soon after birth, resulting in ectopic fat deposition and severe metabolic disturbances. Most cases are caused by AGPAT2 or BSCL2 gene mutations. We aimed to report two unrelated CGL patients with a novel frameshift mutation in AGPAT2 (p.Leu124Serfs*26).

Methods

Clinical features and laboratory were obtained by medical interview and medical records review. DNA was extracted, amplified and sequenced. Mutation Taster was used to estimate the potential biological impact of the AGPAT2 mutations on the protein function.

Results

Patient 1: a 30-year-old woman with lipodystrophy phenotype at birth and diagnosis of diabetes at age 13 presented with severe hypertriglyceridemia and pancreatitis at age 17, hypertension and albuminuria at age 18, proliferative diabetic retinopathy with visual loss at age 25, and an acute myocardial infarction due to multivessel coronary disease during a hospitalization for forefoot amputation at age 29. At this time, she required hemodialysis due to end-stage renal disease. Patient 2: a 12-year-old girl with lipodystrophy phenotype and hypertriglyceridemia detected in the first year of life and abnormalities in the global longitudinal strain, evaluated by speckle-tracking echocardiography last year. Molecular analysis identified a c.369_372delGCTC (p.Leu124Serfs*26) AGPAT2 mutation in both unrelated patients, a compound heterozygous mutation in Patient 1, and homozygous mutation in Patient 2.

Conclusion

We describe two unrelated patients with type 1 CGL due to Leu124Serfs*26, a novel AGPAT2 frameshift mutation, presenting as early cardiovascular disease. These findings suggest an association between Leu124Serfs*26 and a more aggressive phenotype.
Optimal control strategy for the effects of hard water consumption on kidney-related diseases
Authors: Ndii Meksianis Z. , Berkanis Fransiska R. , Tambaru David , Lobo Maria , Ariyanto  , Djahi Bertha S.
Published: April 2020

Objectives 

We study the optimal control strategy for the effects of hard water consumption on kidney-related diseases. The mathematical model has been formulated and studied to gain insights on the optimal control strategy on the effects of hard-water consumption on kidney-related diseases. The positivity and boundedness of the solutions are determined. A global sensitivity analysis has been performed and the numerical solutions have been carried out.

Results 

A global sensitivity analysis shows that the control on water is an important parameter. This can reduce the proportion of individuals with kidney-dysfunction and hence reduces the proportion of individuals with kidney-related diseases. Furthermore, the numerical solutions show that with the optimal control, the proportion of individuals with kidney-related diseases can be minimised.
Mesoscopic population equations for spiking neural networks with synaptic short-term plasticity
Authors: Schmutz Valentin , Gerstner Wulfram , Schwalger Tilo
Published: April 2020

Coarse-graining microscopic models of biological neural networks to obtain mesoscopic models of neural activities is an essential step towards multi-scale models of the brain. Here, we extend a recent theory for mesoscopic population dynamics with static synapses to the case of dynamic synapses exhibiting short-term plasticity (STP). The extended theory offers an approximate mean-field dynamics for the synaptic input currents arising from populations of spiking neurons and synapses undergoing Tsodyks–Markram STP. The approximate mean-field dynamics accounts for both finite number of synapses and correlation between the two synaptic variables of the model (utilization and available resources) and its numerical implementation is simple. Comparisons with Monte Carlo simulations of the microscopic model show that in both feedforward and recurrent networks, the mesoscopic mean-field model accurately reproduces the first- and second-order statistics of the total synaptic input into a postsynaptic neuron and accounts for stochastic switches between Up and Down states and for population spikes. The extended mesoscopic population theory of spiking neural networks with STP may be useful for a systematic reduction of detailed biophysical models of cortical microcircuits to numerically efficient and mathematically tractable mean-field models.
Transgenic plant generated by RNAi-mediated knocking down of soybean Vma12 and soybean mosaic virus resistance evaluation
Authors: Luan Hexiang , Liao Wenlin , Song Yingpei , Niu Haopeng , Hu Ting , Zhi Haijian
Published: April 2020

Soybean mosaic virus (SMV) is one of the most destructive viral diseases in soybean and causes severe reduction of soybean yield and destroys the seed quality. However, the production of SMV resistant plants by transgenic is the most effective and economical means. Based on our previous yeast two-hybrid assay, the GmVma12 was selected as a strong candidate gene for further function characterization. Here we transformed soybean plants with a construct containing inverted repeat of-GmVma12 sequence to analyze the role of GmVma12 during SMV invasion. Totals of 33 T0 and 160 T1 plants were confirmed as positive transgenic plants through herbicide application, PCR detection and LibertyLink® strip screening. Based on the segregation ratio and Southern Blot data, T1 lines No. 3 and No. 7 were selected to generate T2 plants. After SMV-SC15 inoculation, 41 T1 and 38 T2 plants were identified as highly resistant, and their quantification disease levels were much lower than non-transformed plants. The transcript level of GmVma12 in T2 plants decreased to 70% of non-transformed plants. The expression level of SMV-CP transcript in T2 transgenic plants was lower than that in non-transformed plants and SMV CP protein in T2 plants could not be detected by Enzyme-linked Immunosorbent assay, which indicated that SMV production would be inhibited in transgenic plants. Moreover, coat mottles of T2 seeds were obliterated significantly. In conclusion, inverted repeat of the hairpin structure of GmVma12 interfered with the transcription of GmVma12, which can induce resistance to SMV in soybean. This research lays the foundation for the mechanism of SMV pathogenesis, and provides new ideas for SMV prevention and control.
On Hardy-type integral inequalities in the whole plane related to the extended Hurwitz-zeta function
Authors: Rassias Michael Th. , Yang Bicheng , Raigorodskii Andrei
Published: April 2020

Using weight functions, we establish a few equivalent statements of two kinds of Hardy-type integral inequalities with nonhomogeneous kernel in the whole plane. The constant factors related to the extended Hurwitz-zeta function are proved to be the best possible. In the form of applications, we deduce some special cases involving homogeneous kernel. We additionally consider some particular inequalities and operator expressions.