bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis
Authors: Ke Yan , Jiang Wenxue , Xu Yongsheng , Chen Yajun , Zhang Qingsong , Xue Qingyun , Lin Jianhao , Ngai Wilson , Nian Gaowei , Fazeli Mir Sohail , Xie Yao , Zhu Zhenan
Published: May 2021

Background

Single 6 ml Hylan G-F 20 injection, is indicated for knee osteoarthritis patients who have failed to respond to non-pharmacologic therapy and/or simple analgesics. To obtain more thorough understanding of the clinical efficacy and safety, a randomized clinical trial was conducted comparing intra-articular (IA) administration of single 6 ml Hylan G-F 20 injection versus placebo in knee OA patients of Chinese ethnicity.

Methods

This was a randomized, multi-center, double-blind, placebo-controlled clinical trial conducted in 21 centers across China. Four hundred forty adults with knee OA received a single 6 ml Hylan G-F 20 or placebo injection and were evaluated for clinical efficacy and safety outcomes over 26 weeks. Western Ontario and McMaster Universities OA (WOMAC) A1 index, treatment-emergent adverse events (TEAEs) and standard safety parameters were measured at pre-injection, and at weeks 1, 4, 8, 12, 16, 20 and 26 post-injection.

Results

Four hundred forty patients (male: 98 [22.3%]; female: 342 [77.7%]) were randomized. The mean age [standard deviation (SD)] was 61.5 (7.9) years. All patients were of East Asian ethnicity. Mean WOMAC A1 score at baseline was 5.3 (1.2) and 5.2 (1.3) in single 6 ml Hylan G-F 20 injection and placebo groups, respectively. Significant reductions of WOMAC A1 score were observed in both treatment groups when compared to baseline at 26 weeks post-injection, with the mean reduction of [standard error (SE)/percentage] -2.146 (0.108)/− 40.5% and − 2.271 (0.110) /− 43.7% in the single 6 ml Hylan G-F 20 injection and the placebo groups, respectively. Additionally, clinically important reductions in pain at 26 weeks was reported in 67.0 and 68.2% in single 6 ml Hylan G-F 20 injection and placebo groups (p = 0.36). Regarding safety, TEAEs were similar between the two treatment groups (hylan G-F 20 single: 61.5%; placebo: 64.5%).

Conclusions

While the magnitude of the effect of a single 6 ml Hylan G-F 20 injection in this study is consistent with previously published literature with respect to the efficacy and safety of the drug, the current study shows a strong IA placebo effect and did not established superiority of single 6 ml Hylan G-F 20 injection over IA placebo in Chinese knee OA patients.

Trial registration

Prospectively registered Jun 16, 2017 at www.clinicaltrials.gov (NCT03190369).
Association of serum uric acid levels with COVID-19 severity
Authors: Hu Fang , Guo Yifan , Lin Jianghong , Zeng Yingjuan , Wang Juan , Li Man , Cong Li
Published: May 2021

Aims

Hyperuricemia has attracted increasing attention. However, limited concern has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in patients with COVID-19. Therefore, we aim to explore whether patients with COVID-19 had SUA lower than normal and the relationship of SUA and the severity of COVID-19.

Methods

This was a case–control study based on 91 cases with COVID-19 and 273 age- and sex-matched healthy control subjects. We first compared SUA levels and uric acid/creatinine (UA/Cr) ratio between patients with COVID-19 and the healthy controls. Then, we examined the association of SUA levels and UA/Cr ratios with COVID-19 severity in COVID-19 cases only, defined according to the fifth edition of China’s Diagnosis and Treatment Guidelines of COVID-19.

Results

SUA levels in patients with COVID-19 were 2.59% lower, UA/Cr ratios 6.06% lower at admission compared with healthy controls. In sex stratified analysis, levels of SUA and UA/Cr were lower in male patients with COVID-19 while only level of SUA was lower in female patients with COVID-19. Moreover, SUA and UA/Cr values were 4.27 and 8.23% lower in the severe group than that in the moderate group among male COVID-19 patients. Bivariate and partial correlations analysis showed negative correlations between SUA or UA/Cr ratio and COVID-19 after adjusting for age, sex, BMI and eGFR. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent risk factors associated with lower SUA levels. Male patients with COVID-19 accompanied by low SUA levels had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11, 14.72) at admission. Comparing SUA and UA/Cr ratio at three time points (admission, discharge, and follow-up), we found that male patients experienced severe symptoms had lower SUA and UA/Cr ratio levels comparing to moderate patients, but no significant difference between three time points. On the contrary, female patients had lower SUA and UA/Cr ratio at discharge than those at admission, but no significant difference of SUA and UA/Cr ratio between moderate and severe group.

Conclusion

Patients with COVID-19 had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher crude risk of developing severe symptoms than those with high SUA levels. During disease aggravation, the level of SUA gradually decreased until discharge. At the follow-up exam, the level of SUA was similar to the levels at admission.
Bridging the gap between diabetes care and mental health: perspectives of the Mental health IN DiabeteS Optimal Health Program (MINDS OHP)
Authors: Ferrier Lucienne , Ski Chantal F. , O’Brien Casey , Jenkins Zoe , Thompson David R. , Moore Gaye , Ward Glenn , Castle David J.
Published: May 2021

Background

Mental health problems are highly prevalent in people with type 1 diabetes mellitus (T1DM), which adversely impact physical health and quality of life. This study aimed to explore the experiences of people with T1DM who had completed the Mental health IN DiabeteS Optimal Health Program (MINDS OHP), a novel intervention developed to bridge the gap between physical and mental health care.

Method

Participants with T1DM were invited to take part in a focus group or semi-structured interviews. Participants were recruited from outpatient and community settings. The focus group and interviews were audio-recorded and transcribed verbatim. Thematic content analysis was used and identified themes were cross-validated by researchers and member-checked by participants.

Results

Ten people with T1DM were included. Two key themes emerged: ‘MINDS OHP experiences’ and ‘lived experiences of diabetes’. MINDS OHP experiences included five sub-themes: program benefits, follow-up and timing, suggested improvements, collaborative partners, and materials suitability. Lived experiences also included five sub-themes: bridging the gap between mental and physical health, support networks, stigma and shame, management intrusiveness, and adolescence and critical life points.

Conclusions

The MINDS OHP for people with T1DM was generally well received, though study findings suggest a number of improvements could be made to the program, such as including family members, and consideration being given to its routine early inclusion in diabetes management, ideally in primary care.
Ocular tuberculosis in a calf.
Authors: Carrisoza-Urbina Jacobo , Bedolla-Alva Mario A. , Juárez-Ramírez Mireya , Gutiérrez-Pabello José A.
Published: May 2021

Background

Bovine tuberculosis is a chronic inflammatory disease that causes granuloma formation mainly in retropharyngeal, tracheobronchial, mediastinal lymph nodes and lungs of bovines. The presence of these lesions in other tissues such as the eyeball is very rare and difficult to diagnose. This study describes macroscopic and microscopic pathological findings in a calf with ocular and meningeal tuberculosis.

Case presentation

March 2019, an eight-month-old Holstein Friesian calf was identified in a dairy farm located in central Mexico with a clinical cough, anorexia, incoordination, corneal opacity and vision loss. At necropsy, pneumonia, lymphadenitis, meningitis, and granulomatous iridocyclitis were observed. The histopathological examination revealed granulomatous lesions in lung tissue, lymph nodes, meninges and eyes with the presence of acid-fast bacilli associated with Mycobacterium spp.

Conclusion

To the best of our knowledge, this is the first report that describes macroscopic and microscopic pathological findings of ocular tuberculosis in cattle. This report highlights the importance of considering bovine tuberculosis in the differential diagnosis of corneal opacity and loss of vision in cattle.
Effect of mesenchymal stromal cell infusions on lung function in COPD patients with high CRP levels
Authors: Weiss Daniel J. , Segal Karen , Casaburi Richard , Hayes Jack , Tashkin Donald
Published: May 2021

Background

We previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD. While safety profile was good, no functional efficacy was observed. However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels.

Methods

Time course of lung function, exercise performance, patient reported responses, and exacerbation frequency following four monthly infusions of remestemcel-L vs. placebo were re-assessed in subgroups based on baseline circulating CRP levels.

Results

In COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion. Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L. These improvements persisted variably over the 2-year observational period. No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups.

Conclusion

In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases.

Trial registration: Clinicaltrials.gov NCT00683722.
Surfactant protein D and bronchopulmonary dysplasia: a new way to approach an old problem
Authors: Arroyo Raquel , Kingma Paul S.
Published: May 2021

Surfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. SP-D participates in the innate immune defense of the lungs by helping to clear infectious pathogens and modulating the immune response. SP-D has shown an anti-inflammatory role by down-regulating the release of pro-inflammatory mediators in different signaling pathways such as the TLR4, decreasing the recruitment of inflammatory cells to the lung, and modulating the oxidative metabolism in the lungs. Recombinant human SP-D (rhSP-D) has been successfully produced mimicking the structure and functions of native SP-D. Several in vitro and in vivo experiments using different animal models have shown that treatment with rhSP-D reduces the lung inflammation originated by different insults, and that rhSP-D could be a potential treatment for bronchopulmonary dysplasia (BPD), a rare disease for which there is no effective therapy up to date. BPD is a complex disease in preterm infants whose incidence increases with decreasing gestational age at birth. Lung inflammation, which is caused by different prenatal and postnatal factors like infections, lung hyperoxia and mechanical ventilation, among others, is the key player in BPD. Exacerbated inflammation causes lung tissue injury that results in a deficient gas exchange in the lungs of preterm infants and frequently leads to long-term chronic lung dysfunction during childhood and adulthood. In addition, low SP-D levels and activity in the first days of life in preterm infants have been correlated with a worse pulmonary outcome in BPD. Thus, SP-D mediated functions in the innate immune response could be critical aspects of the pathogenesis in BPD and SP-D could inhibit lung tissue injury in this preterm population. Therefore, administration of rhSP-D has been proposed as promising therapy that could prevent BPD.
Exosomal microRNAs in hepatocellular carcinoma
Authors: Liu Chenbin , Wu Han , Mao Yinqi , Chen Wei , Chen Shuying
Published: May 2021

Hepatocellular carcinoma is one of the most common malignant tumors worldwide and the fourth leading cause of cancer-related deaths. The prognosis of hepatocellular carcinoma patients is extremely poor due to the occult onset and high metastasis of hepatocellular carcinoma. Therefore, biomarkers with high specificity and sensitivity are of great importance in early screening, diagnosis prognosis, and treatment of hepatocellular carcinoma patients. Exosomes are tiny vesicles secreted by various types of cells, which can serve as mediators of intercellular communication to regulate the tumor microenvironment, and play a key role in the occurrence, development, prognosis, monitor and treatment of hepatocellular carcinoma. As microRNA deliverer, exosomes are involved in multiple life activities by regulating target genes of recipient cells such as proliferation, invasion, metastasis and apoptosis of cancer cells. In this review, we summarized the composition, active mechanism and function of exosomal microRNAs in hepatocellular carcinoma, and elaborated on their potential application value of early diagnosis and treatment in hepatocellular carcinoma.
Perceptions about the accessibility of healthcare services among ethnic minority women: a qualitative study among Arab Bedouins in Israel
Authors: Shibli Haneen , Aharonson-Daniel Limor , Feder-Bubis Paula
Published: May 2021

Background

Access to healthcare services has major implications for vulnerable populations’ health. Socio-cultural and gender characteristics shape the utilization and access of healthcare services among ethnic minorities worldwide. One such vulnerable ethnic minority is the Arab Bedouin women in Israel. As women, they are marginalized in their community, where women do not have full equity and they experience multiple barriers to healthcare services The main objective of this study is to provide a nuanced, experiential, emic description of healthcare accessibility issues among Bedouin women in Israel. Identifying the barriers, they face in accessing healthcare may help healthcare policymakers make changes based on and tailored to Bedouin women’s needs.

Methods

A qualitative study included in-depth semi-structured interviews with 21 Arab Bedouin village residents, consisting of 14 women and 7 men. Eligible participants were Arab Bedouins over 18 years of age and who used healthcare services at least once in the last 5 years. The interviews were carried out in Arabic-Bedouin dialect and included demographic questions, open-ended questions that asked about participants’ perceptions regarding their experiences with healthcare services, including the factors that helped and hindered them in accessing these services and questions regarding suggestions for improving the accessibility of healthcare services based on the identified needs. Data collected were analyzed using thematic analysis. Study trustworthiness was ensured using audit, reflexivity, and peer debriefing.

Results

Arab Bedouin women experienced varied barriers while accessing healthcare services. This study uncovered how language, cultural and gender barriers intersect with other disadvantages ingrained in social norms, values and beliefs and affect the access of a minority women subgroup to healthcare services. The participants identified subgroups of Bedouin women (e.g. elderly Bedouin women) affected differently by these barriers.

Conclusion

Taking into consideration the identified needs and the Arab Bedouin women’s unique characteristics, along with adopting the intersectional approach should help improve access to healthcare services among such a vulnerable subgroup and other subgroups within minorities worldwide.
Electrospun fibrous sponge via short fiber for mimicking 3D ECM
Authors: Li Yan , Wang Juan , Qian Dejian , Chen Liang , Mo Xiumei , Wang Lei , Wang Yan , Cui Wenguo
Published: May 2021

Background

Most of the natural extracellular matrix (ECM) is a three-dimensional (3D) network structure of micro/nanofibers for cell adhesion and growth of 3D. Electrospun fibers distinctive mimicked 2D ECM, however, it is impossible to simulate 3D ECM because of longitudinal collapse of continuous micro/nanofibers. Herein, 3D electrospun micro/nano-fibrous sponge was fabricated via electrospinning, homogenization, shaping and thermal crosslinking for 3D tissue regeneration of cells and vascular.

Results

Fibrous sponge exhibited high porosity, water absorption and compression resilience and no chemical crosslinked agent was used in preparation process. In vitro studies showed that the 3D short fiber sponge provided an oxygen-rich environment for cell growth, which was conducive to the 3D proliferation and growth of HUVECs, stimulated the expression of VEGF, and well promoted the vascularization of HUVECs. In vivo studies showed that the 3D short fiber sponges had a good 3D adhesion to the chronic wound of diabetes in rats. Furthermore, 3D short fibrous sponges were better than 2D micro/nanofiber membranes in promoting the repair of diabetic full-thickness skin defects including wound healing, hair follicle regeneration, angiogenesis, collagen secretion.

Conclusion

Therefore, electrospun short fibrous sponges are special candidates for mimicking the 3D ECM and promoting 3D regeneration of tissue.

Graphic Abstract
Combined effect of vitamin C and vitamin D3 on intestinal epithelial barrier by regulating Notch signaling pathway
Authors: Qiu Fubin , Zhang Zehui , Yang Linxue , Li Rui , Ma Ying
Published: May 2021

Background

Tight junction proteins play crucial roles in maintaining the intestinal mucosal barrier. Although previous studies have shown that Notch signaling is closely related to tight junction proteins, the mechanism remains unclear. This study was performed to investigate whether vitamin C combined with vitamin D3 affects intestinal mucosal barrier stability via the Notch signaling pathway.

Methods

Intestinal epithelial barrier and notch signaling pathway were studied using guinea pig and SW480 cells. The guinea pigs were randomized into four groups (n = 6 in each group): control group (C, 200 IU/kg d VD3 + 100 mg/kg d VC), low VC group (LVC, 200 IU/kg d VD3 + 10 mg/kg d VC), medium VC group (MVC, 200 IU/kg d VD3 + 100 mg/kg d VC), and high VC group (HVC, 200 IU/kg d VD3 + 200 mg/kg d VC). Except for the control group, the other three groups were freely drinked with 2% dextran sodium sulfate solution for 4 days. And the control group was free to drink distilled water. The following cell groups were used: control group (SW480 cells without intervention); LPS group (100 ng/mL LPS); VD3 group (0.1 μmol/L VD3); VC + VD3 group (0.1, 1, 5, 10 μmol/mL VC + 0.1 μmol/L VD3).

Results

Electron microscopy analysis revealed that both low and high doses of vitamin C combined with vitamin D3 maintained dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal epithelium tight junction. Compared with the control group, the expression level of ZO-1 mRNA in the colon tissue of the high-dose vitamin C group was significantly increased. In SW480 cell experiments, compared with the control group, cell migration and repair following treatment with different concentrations of vitamin C combined with vitamin D3 were significantly improved and the protein expression of Notch-1 was increased, whereas the protein expression of claudin-2 was significantly decreased. Thus, our results demonstrate that an appropriate amount of vitamin C combined with vitamin D3 can regulate the expression of claudin-2 by regulating Notch-1, relieve destruction of the intestinal mucosal barrier, and promote the repair of damage to the cell mucosal barrier.

Conclusions

We found that vitamin C combined with vitamin D3 protected against dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal mucosa.
Clinico-Hematological and cytogenetic spectrum of adult myelodysplastic syndrome: The first retrospective cross-sectional study in Iranian patients
Authors: Paridar Mostafa , Zibara Kazem , Ahmadi Seyed Esmaeil , Khosravi Abbas , Soleymani Maral , Azizi Ebrahim , Ghalesardi Omid Kiani
Published: May 2021

Background

Myelodysplastic syndrome (MDS), a heterogeneous group of hematopoietic malignancy, has been shown to present different cytogenetic abnormalities, risk factors, and clinico-hematological features in different populations and geographic areas. Herein, we determined the cytogenetic spectrum and clinico-hematological features of Iranian MDS patients for the first time.

Methods

This prospective cross-sectional study was conducted on 103 patients with MDS in Ahvaz, southwest of Iran, from 2014 to 2018. Clinical presentations, complete blood counts (CBC), and bone marrow (BM) biopsy samples were assessed. Perls' staining was used to evaluate BM iron storage. The cytogenetic evaluation was performed using the conventional G banding method on the BM.

Results

Patients’ median age was 62.3 (ranged from 50–76), and the majority were male (72.8%). The most common clinical symptom at the time of admission was fatigue (n = 33) followed by pallor (n = 27). The most common subgroup was MDS-Multi Lineage Dysplasia (MDS-MLD) (n = 38, 36.8%), followed by MDS-Single Lineage Dysplasia (MDS-SLD) (n = 28, 18.4%). A normal karyotype was observed in 59 patients (57.3%), while 44 patients (42.7%) had cytogenetic abnormalities. Trisomy 8 (+ 8) was the most common cytogenetic abnormality (n = 14) followed by del 17p (n = 9) and monosomy 7 (− 7) (n = 7). Twelve patients (11.65%) were transformed to AML.

Conclusion

Our data betokened that among our MDS patients, Trisomy 8 is the predominant cytogenetic abnormality, and MDS-MLD and MDS-SLD are the most common of subtypes. Noteworthy, the male: female ratio was slightly higher in Iran than in previous reports from other parts of the world. Our study is the first report of the clinical, hematological, and cytogenetic spectrum of MDS patients in Iran
The cost of community research—recruiting community-dwelling participants to a feasibility primary care cluster randomised controlled trial
Authors: Harrison Nicola , Brundle Caroline , Heaven Anne , Clegg Andrew
Published: May 2021

Background

To support a robust evidence base for the organisation and provision of community-delivered health services for older people, clinical trials need to be designed to account for community-based participant recruitment. There is currently little reported information available on the time and cost of recruiting community-dwelling older people, which makes the completion of cost attribution documentation problematic when applying for research funding.

Main body

We aimed to establish the amount of researcher time it takes to recruit community-dwelling older people to a feasibility primary care cluster randomised controlled trial, including collecting baseline data. The trial was part of a programme of work investigating an intervention to improve the quality of life for older people with frailty. Two researchers conducting home visits to recruit and collect baseline data from participants recorded the time spent on travelling to and from the visit, at the visit itself and any associated administration. The median total researcher activity time per visit was 148 min. We discuss the various elements of recruitment and data collection activity and the factors that impacted the length of time taken, including location, individuals’ capacity and cognition, hearing and visual impairment and the desire for social contact.

Conclusion

Studies cannot reach their recruitment targets if they are unrealistically planned and resourced. We recommend that trials recruiting older people in the community allocate two and a half hours of researcher time per person, on average, for consent, baseline data collection, travel and administration. We acknowledge that a variety of different factors will mean that researcher activity will vary between different community-based trials. Our findings give a good starting point for timing calculations, and evidence on which to base the justification of research activity costings.

Trial registration

Personalised care planning for older people with frailty ISRCTN12363970. 08/11/2018.
The role of mycobiota-genotype association in inflammatory bowel diseases: a narrative review
Authors: Mahmoudi Elaheh , Mozhgani Sayed-Hamidreza , Sharifinejad Niusha
Published: May 2021

Inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting various parts of the gastrointestinal tract. A majority of the current evidence points out the involvement of intestinal dysbiosis in the IBD pathogenesis. Recently, the association of intestinal fungal composition With IBD susceptibility and severity has been reported. These studies suggested gene polymorphisms in the front line of host defense against intestinal microorganisms are considered to play a role in IBD pathogenesis. The studies have also detected increased susceptibility to fungal infections in patients carrying IBD-related mutations. Therefore, a literature search was conducted in related databases to review articles addressing the mycobiota-genotype association in IBD.
Correction to: Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life
Authors: Jiménez Jessica A. , Ptacek Travis S. , Tuttle Alex H. , Schmid Ralf S. , Moy Sheryl S. , Simon Jeremy M. , Zylka Mark J.
Published: May 2021

An amendment to this paper has been published and can be accessed via the original article.
An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults
Authors: Weir Elizabeth , Allison Carrie , Ong Ken K. , Baron-Cohen Simon
Published: May 2021

Background

Studies of autistic children suggest that restricted eating, reduced physical activity, and sleep disorders are common; however, no studies attempt to broadly describe the diet, exercise, and sleep patterns of autistic adults or consider relationships between lifestyle behaviors and the widely reported increased risks of obesity and chronic conditions. To address this, the authors developed the largest study of lifestyle patterns of autistic adults and assessed their relationships to body mass index, health outcomes, and family history.

Methods

We administered an anonymized, online survey to n = 2386 adults (n = 1183 autistic) aged 16–90 years of age. We employed Fisher’s exact tests and binomial logistic regression to describe diet, exercise, and sleep patterns; mediation of seizure disorders on sleep; body mass index (BMI); relationships of lifestyle factors to BMI, cardiovascular conditions, and diabetic conditions; and sex differences among autistic adults.

Results

Autistic adults, and particularly autistic females, exhibit unhealthy diet, exercise, and sleep patterns; they are also more likely to be underweight or obese. Limited sleep duration and high rates of sleep disturbances cannot be accounted for by epilepsy or seizure disorders. Lifestyle factors are positively related to higher risk of cardiovascular conditions among autistic males, even more than family history.

Limitations

Our sample may not be representative of all autistic and non-autistic people, as it primarily comprised individuals who are white, female, have a high school education or higher, and reside in the UK. Our sampling methods may also exclude some individuals on the autism spectrum, and particularly those with moderate to severe intellectual disability. This is a cross-sectional sample that can test for relationships between factors (e.g., lifestyle factors and health outcomes) but cannot assess the direction of these relationships.

Conclusions

Autistic adults are less likely to meet minimal health recommendations for diet, exercise, and sleep—and these unhealthy behaviors may relate to excess risk of cardiovascular conditions. Although the present study can only provide preliminary, correlational evidence, our findings suggest that diet, exercise, and sleep should be considered and further investigated as key targets for reducing the now widely reported and dramatically increased risks of health comorbidity and premature death among autistic individuals compared to others. Physicians should work cooperatively with patients to provide health education and develop individualized strategies for how to better manage challenges with diet, exercise, and sleep.
Perspectives for improvement of Mycoplasma hyopneumoniae vaccines in pigs
Authors: Maes Dominiek , Boyen Filip , Devriendt Bert , Kuhnert Peter , Summerfield Artur , Haesebrouck Freddy
Published: May 2021

Mycoplasma hyopneumoniae(M. hyopneumoniae) is one of the primary agents involved in the porcine respiratory disease complex, economically one of the most important diseases in pigs worldwide. The pathogen adheres to the ciliated epithelium of the trachea, bronchi, and bronchioles, causes damage to the mucosal clearance system, modulates the immune system and renders the animal more susceptible to other respiratory infections. The pathogenesis is very complex and not yet fully understood. Cell-mediated and likely also mucosal humoral responses are considered important for protection, although infected animals are not able to rapidly clear the pathogen from the respiratory tract. Vaccination is frequently practiced worldwide to controlM. hyopneumoniaeinfections and the associated performance losses, animal welfare issues, and treatment costs. Commercial vaccines are mostly bacterins that are administered intramuscularly. However, the commercial vaccines provide only partial protection, they do not prevent infection and have a limited effect on transmission. Therefore, there is a need for novel vaccines that confer a better protection. The present paper gives a short overview of the pathogenesis and immune responses followingM. hyopneumoniaeinfection, outlines the major limitations of the commercial vaccines and reviews the different experimentalM. hyopneumoniaevaccines that have been developed and tested in mice and pigs. Most experimental subunit, DNA and vector vaccines are based on the P97 adhesin or other factors that are important for pathogen survival and pathogenesis. Other studies focused on bacterins combined with novel adjuvants. Very few efforts have been directed towards the development of attenuated vaccines, although such vaccines may have great potential. As cell-mediated and likely also humoral mucosal responses are important for protection, new vaccines should aim to target these arms of the immune response. The selection of proper antigens, administration route and type of adjuvant and carrier molecule is essential for success. Also practical aspects, such as cost of the vaccine, ease of production, transport and administration, and possible combination with vaccines against other porcine pathogens, are important. Possible avenues for further research to develop better vaccines and to achieve a more sustainable control ofM. hyopneumoniaeinfections are discussed.
Epidemiology and evolution of Middle East respiratory syndrome coronavirus, 2012–2020
Authors: Zhang An-Ran , Shi Wen-Qiang , Liu Kun , Li Xin-Lou , Liu Ming-Jin , Zhang Wen-Hui , Zhao Guo-Ping , Chen Jin-Jin , Zhang Xiao-Ai , Miao Dong , Ma Wei , Liu Wei , Yang Yang , Fang Li-Qun
Published: May 2021

Background

The ongoing transmission of the Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East and its expansion to other regions are raising concerns of a potential pandemic. An in-depth analysis about both population and molecular epidemiology of this pathogen is needed.

Methods

MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports, supplemented by other reliable sources. Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models, respectively. Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV.

Results

A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7% (95% CI: 30.9‒34.6%). Saudi Arabia accounted for 83.6% of the cases. Age of ≥ 65 years old, underlying conditions and ≥ 5 days delay in diagnosis were independent risk factors for death. However, a history of animal contact was associated with a higher risk (adjusted OR = 2.97, 95% CI: 1.10–7.98) among female cases < 65 years but with a lower risk (adjusted OR = 0.31, 95% CI: 0.18–0.51) among male cases ≥ 65 years old. Diffusion of the disease was fastest from its origin in Saudi Arabia to the east, and was primarily driven by the transportation network. The most recent sub-clade C5.1 (since 2013) was associated with non-synonymous mutations and a higher mortality rate. Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV.

Conclusions

MERS-CoV remains primarily locally transmitted in the Middle East, with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases. Animal contact is associated with a higher risk of death, but the association differs by age and sex. Transportation network is the leading driver for the spatial diffusion of the disease. These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic.

Graphical abstract
Early onset senescence and cognitive impairment in a murine model of repeated mTBI
Authors: Schwab Nicole , Ju YoungJun , Hazrati Lili-Naz
Published: May 2021

Mild traumatic brain injury (mTBI) results in broad neurological symptoms and an increased risk of being diagnosed with a neurodegenerative disease later in life. While the immediate oxidative stress response and post-mortem pathology of the injured brain has been well studied, it remains unclear how early pathogenic changes may drive persistent symptoms and confer susceptibility to neurodegeneration. In this study we have used a mouse model of repeated mTBI (rmTBI) to identify early gene expression changes at 24 h or 7 days post-injury (7 dpi). At 24 h post-injury, gene expression of rmTBI mice shows activation of the DNA damage response (DDR) towards double strand DNA breaks, altered calcium and cell–cell signalling, and inhibition of cell death pathways. By 7 dpi, rmTBI mice had a gene expression signature consistent with induction of cellular senescence, activation of neurodegenerative processes, and inhibition of the DDR. At both timepoints gliosis, microgliosis, and axonal damage were evident in the absence of any gross lesion, and by 7 dpi rmTBI also mice had elevated levels of IL1β, p21, 53BP1, DNA2, and p53, supportive of DNA damage-induced cellular senescence. These gene expression changes reflect establishment of processes usually linked to brain aging and suggests that cellular senescence occurs early and most likely prior to the accumulation of toxic proteins. These molecular changes were accompanied by spatial learning and memory deficits in the Morris water maze. To conclude, we have identified DNA damage-induced cellular senescence as a repercussion of repeated mild traumatic brain injury which correlates with cognitive impairment. Pathways involved in senescence may represent viable treatment targets of post-concussive syndrome. Senescence has been proposed to promote neurodegeneration and appears as an effective target to prevent long-term complications of mTBI, such as chronic traumatic encephalopathy and other related neurodegenerative pathologies.
Mechanical zonation of rock properties and the development of fluid migration pathways: implications for enhanced geothermal systems in sedimentary-hosted geothermal reservoirs
Authors: Kolawole Oladoyin , Ispas Ion , Kolawole Folarin , Germay Christophe , McLennan John D.
Published: May 2021

Oil and gas operations in sedimentary basins have revealed the occurrence of significant temperature anomalies at depth, raising the possibility of major geothermal resource potential in the sedimentary sequences. The efficient development of such a resource may require enhancement by hydraulic stimulation. However, effective stimulation relies on an initial assessment of in situ mechanical properties and a model of the rock response. Here, we examine the distribution of mechanical properties (unconfined compressive strength, UCS; ultrasonic velocity-derived Poisson ratio, ν; and, scratch toughness, Ks) along the cored interval of a sedimentary formation with a known low-to-medium temperature geothermal anomaly in the Permian Basin, U.S. Our results reveal the presence of mechanical stratigraphy along the core, demonstrated by the alternation of distinct soft–hard (i.e.,less stiff-to-stiff) mechanical zone couplets composed of: (1) mechanically softer 0.17-m-thick Zone-A and 0.18-m-thick Zone-C with mean values of UCS = 110 MPa, ν = 0.25, Ks = 1.89 MPa·√m; and (2) mechanically harder 0.41-m-thick Zone-B and 0.15-m-thick Zone-D which show mean values of UCS = 166 MPa, ν = 0.22, and Ks = 2.87 MPa·√m. Although X-ray diffraction analyses of the samples suggest that the entire rock matrix is dominated by dolomite, the harder zones show an abundance of quartz cement (> 30%) and relatively lower phyllosilicate mineral content (< 2%) than the softer zones. Further, we observe that the mechanically harder zones have the greatest occurrences and thicknesses of hydrothermal alterations (anhydrite veins and nodules), indicating that the rock had experienced hydrothermal fluid circulation (basinal brines) in the past. We infer that the mechanical stratigraphy most likely influenced the spatial clustering of fractures that facilitated hydrothermal fluid migration in the past, and provides insight that is relevant for the exploitation of geothermal energy resources in sedimentary basins. We suggest that the harder zones or formation intervals with higher ratios of the hard zones relative to soft zones represent viable targets for hydraulic stimulation of a sedimentary-hosted geothermal reservoir, both for the emplacement of new fractures and the linkage of pre-existing fractures to allow efficient fluid circulation. Our findings in this study provide insight that is relevant for understanding the complexity of pre-existing mechanical heterogeneity in sedimentary-hosted geothermal reservoir targets in other places.
β1-blocker in sepsis
Authors: Hasegawa Daisuke , Sato Ryota , Nishida Osamu
Published: May 2021

Background

The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical evidence of ultrashort-acting β1-blockers.

Main body

A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation.

Conclusion

Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted.
Quantitative investigation of memory recall performance of a computational microcircuit model of the hippocampus
Authors: Andreakos Nikolaos , Yue Shigang , Cutsuridis Vassilis
Published: May 2021

Memory, the process of encoding, storing, and maintaining information over time to influence future actions, is very important in our lives. Losing it, it comes with a great cost. Deciphering the biophysical mechanisms leading to recall improvement should thus be of outmost importance. In this study, we embarked on the quest to improve computationally the recall performance of a bio-inspired microcircuit model of the mammalian hippocampus, a brain region responsible for the storage and recall of short-term declarative memories. The model consisted of excitatory and inhibitory cells. The cell properties followed closely what is currently known from the experimental neurosciences. Cells’ firing was timed to a theta oscillation paced by two distinct neuronal populations exhibiting highly regular bursting activity, one tightly coupled to the trough and the other to the peak of theta. An excitatory input provided to excitatory cells context and timing information for retrieval of previously stored memory patterns. Inhibition to excitatory cells acted as a non-specific global threshold machine that removed spurious activity during recall. To systematically evaluate the model’s recall performance against stored patterns, pattern overlap, network size, and active cells per pattern, we selectively modulated feedforward and feedback excitatory and inhibitory pathways targeting specific excitatory and inhibitory cells. Of the different model variations (modulated pathways) tested, ‘model 1’ recall quality was excellent across all conditions. ‘Model 2’ recall was the worst. The number of ‘active cells’ representing a memory pattern was the determining factor in improving the model’s recall performance regardless of the number of stored patterns and overlap between them. As ‘active cells per pattern’ decreased, the model’s memory capacity increased, interference effects between stored patterns decreased, and recall quality improved.
Human amniotic membrane for the treatment of large and refractory macular holes: a retrospective, multicentric, interventional study
Authors: Ferreira Magno A. , Maia André , Machado André J. , Ferreira Raquel E. A. , Hagemann Luiz Felipe , Júnior Pedro Hélio E. Ribeiro , Rezende Flávio A.
Published: May 2021

Background

The purpose of the current study is to report the anatomical and functional results of off-label human amniotic membrane graft as primary intervention to repair large to giant macular holes and in reoperations when wide internal limiting membrane peeling was unsuccessful.

Methods

Retrospective chart review was carried out in five different centers to identify all cases that had undergone off-label human amniotic membrane graft for the treatment of large or failed macular holes (MH). Data collected included age, gender, other concomitant diagnosis, symptoms duration, lens status, number of previous surgeries, macular hole measurements (minimum and base linear diameters), mean post-operative follow-up (months), and pre- and post-operative best corrected visual acuity (BCVA). Main outcome measures were anatomical MH closure rates and final BCVA (in logMAR). Nonparametric Wilcoxon rank-sum test was used because the data was not normally distributed, a P values < 0.05 were considered statistically significant.

Results

Nineteen eyes of 19 patients were identified and included in the study. Mean age was 66.21 ± 14.96 years and predominantly females (84%). All eyes had successfully closed MH with a single intervention with no recurrences during a mean of 9 ± 3.87 months follow-up. The median BCVA in logMAR preoperative was 1.30 ± 0.44 (0.80–2.0), approximately 20/400 on Snellen chart and the median BCVA in logMAR postoperative was 1.0 ± 0.72 (0.4–3.0) approximately 20/200 (p < 0.0001) with median of three lines of visual improvement.

Conclusion

The use of human amniotic membrane graft seems to be a viable and effective alternative for the treatment of large and persistent macular holes. However, further larger prospective controlled studies are necessary to confirm our preliminary results of this new surgical technique.
Cultural influence on innovativeness - links between “The Culture Map” and the “Global Innovation Index”
Authors: Nyssen Guillén Viola Isabel , Deckert Carsten
Published: May 2021

In the ongoing debate on the relation of cultural differences and national innovativeness this research aims to find out which of the seven cultural dimensions of The Culture Map (communicating, evaluating, leading, deciding, trusting, disagreeing, scheduling) have a significant influence on a nation’s ability and capacity to innovate. The findings show that cultural aspects as described by The Culture Map clearly influence the innovativeness of a nation. Based on these findings, tentative recommendations for fruitful monocultural and multicultural teams respectively are given.