bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinally projecting noradrenergic neurons of the locus coeruleus display resistance to AAV2retro-mediated transduction
Authors: Ganley Robert P , Werder Kira , Wildner Hendrik , Zeilhofer Hanns Ulrich
Published: August 2021

Background

The locus coeruleus (LC) is the principal source of noradrenaline (NA) in the central nervous system. Projection neurons in the ventral portion of the LC project to the spinal cord and are considered the main source of spinal NA. To understand the precise physiology of this pathway, it is important to have tools that allow specific genetic access to these descending projections. AAV2retro serotype vectors are a potential tool to transduce these neurons via their axon terminals in the spinal cord, and thereby limit the expression of genetic material to the spinal projections from the LC. Here, we assess the suitability of AAV2retro to target these neurons and investigate strategies to increase their labelling efficiency.

Results

We show that the neurons in the LC that project to the spinal dorsal horn are largely resistant to transduction with AAV2retro serotype vectors. Compared to Cholera toxin B (CTb) tracing, AAV2retro.eGFP labelled far fewer neurons within the LC and surrounding regions, particularly within neurons that express tyrosine hydroxylase (TH), the rate-limiting enzyme for NA synthesis. We also show that the sensitivity for transduction of this projection can be increased using AAV2retro.eGFP.cre in ROSA26tdTom reporter mice (23% increase), with a higher proportion of the newly revealed neurons expressing TH compared to those directly labelled with AAV2retro containing an eGFP expression sequence.

Conclusion

These tracing studies identify limitations in AAV2retro-mediated retrograde transduction of a subset of projection neurons, specifically those that express NA and project to the spinal cord. This is likely to have implications for the study of NA-containing projections as well as other types of projection neuron in the central nervous system.
Structures contributing to the shoulder contracture in brachial plexus birth palsy. An intraoperative biomechanical study
Authors: Jönsson Krister , Roos Fredrik , Hultgren Tomas
Published: August 2021

Internal rotation contracture of the shoulder is a common sequel of the brachial plexus birth palsy. The purpose of this study is to describe the surgical method used in our centre and to measure the effect of sequentially releasing several anatomical structures that have been ascribed as the cause of the contracture. Twenty-four consecutive patients were operated on with an open release. We documented the increase in passive external rotation after each surgical step. We found small gains in passive external rotation when performing coracoidectomy and division of the upper part of the subscapularis tendon; 4° (95% confidence interval [CI] 2°–6° p < 0.01) and 6° (95% CI 4°–8° p < 0.01), respectively. A substantial gain in external rotation occurred when dividing the entire subscapularis tendon, 43° (95% CI 38°–48°, p < 0.01). Our findings indicate that a clinically relevant surgical release of the contracture requires lengthening of the entire subscapularis musculo-tendinous unit.

Level of evidence: IV
A non-interventional switch study in adult patients with asthma or COPD on clinical effectiveness of salmeterol/fluticasone Easyhaler® in routine clinical practice
Authors: Vinge Ines , Syk Jörgen , Xanthopoulos Athanasios , Laßmann Hendrik , Vahteristo Mikko , Sairanen Ulla , Lähelmä Satu , Hennig Rudolf , Müller Matthias
Published: August 2021

Background:

Selection of the most appropriate device for a switch from one inhaler to an equivalent product is known to have a major impact on clinical outcomes in patients with asthma or chronic obstructive pulmonary disease (COPD). Salmeterol/fluticasone propionate (S/F) Easyhaler® has been demonstrated to be therapeutically equivalent with a reference product. However, no data on real-life effectiveness are currently available for patients switching to S/F Easyhaler from another S/F inhaler.

Methods:

The aim of this prospective, open, multicenter, non-interventional study was to assess clinical effectiveness of propionate S/F Easyhaler in adult asthma and COPD patients switched from another inhaler. The primary endpoints were Asthma Control Test (ACT) and COPD Assessment Test (CAT). Secondary endpoints included assessments of patient satisfaction and preference and physician/nurse perception on S/F Easyhaler use. The study included three visits during a 12-week follow-up.

Results:

A total of 211 patients (160 with asthma; 51 with COPD) were included in the analyses. In patients with asthma, there was a statistically significant increase in the mean ACT score at week 12 (20.2 ± 3.9) compared with the baseline (18.6 ± 4.1), with a mean increase of 1.6 (±3.5) points ( p < 0.0001). In patients with COPD, CAT score persisted from baseline (19.9 ± 8.6) to week 12 (19.6 ± 7.0). Patients were significantly more satisfied with Easyhaler and most patients preferred Easyhaler over their previous inhaler. The physicians/nurses reported that it was ‘very easy’ to teach the use of Easyhaler and the training took less than 5 minutes in most cases.

Conclusion:

The results from this prospective real-life clinical study indicate better or at least similar treatment control of asthma and COPD after switching to S/F Easyhaler from another S/F inhaler. This study also shows that S/F Easyhaler was favored by the patients and that it is easy to teach, learn and use in a real-life setting. The reviews of this paper are available via the supplemental material section.
The role of chromodomain helicase DNA binding protein 1 (CHD1) in promoting an invasive prostate cancer phenotype
Authors: Kareddula Aparna , Medina Daniel J. , Petrosky Whitney , Dolfi Sonia , Tereshchenko Irina , Walton Kelly , Aviv Hana , Sadimin Evita , Tabakin Alexandra L. , Singer Eric A. , Hirshfield Kim M.
Published: August 2021

Background:

Prostate cancer (PCa) phenotypes vary from indolent to aggressive. Molecular subtyping may be useful in predicting aggressive cancers and directing therapy. One such subtype involving deletions of chromodomain helicase DNA binding protein 1 ( CHD1), a tumor suppressor gene, are found in 10–26% of PCa tumors. In this study, we evaluate the functional cellular effects that follow CHD1 deletion.

Methods:

CHD1 was knocked out (KO) in the non-tumorigenic, human papillomavirus 16 (HPV16)-immortalized prostate epithelial cell line, RWPE-1, using CRISPR/Cas9. In vitro assays such as T7 endonuclease assay, western blot, and sequencing were undertaken to characterize the CHD1 KO clones. Morphologic and functional assays for cell adhesion and viability were performed. To study expression of extracellular matrix (ECM) and adhesion molecules, a real-time (RT) profiler assay was performed using RWPE-1 parental, non-target cells (NT2) and CHD1 KO cells.

Result:

Compared to parental RWPE-1 and non-target cells (NT2), the CHD1 KO cells had a smaller, rounder morphology and were less adherent under routine culture conditions. Compared to parental cells, CHD1 KO cells showed a reduction in ECM and adhesion molecules as well as a greater proportion of viable suspension cells when cultured on standard tissue culture plates and on plates coated with laminin, fibronectin or collagen I. CHD1 KO cells showed a decrease in the expression of secreted protein acidic and rich in cysteine (SPARC), matrix metalloproteinase 2 (MMP2), integrin subunit alpha 2 (ITGA2), integrin subunit alpha 5 (ITGA5), integrin subunit alpha 6 (ITGA6), fibronectin (FN1), laminin subunit beta-3 precursor (LAMB3), collagen, tenascin and vitronectin as compared to parental and NT2 cells.

Conclusion:

These data suggest that in erythroblast transformation specific (ETS) fusion-negative, phosphatase and tensin homolog ( PTEN) wildtype PCa, deletion of CHD1 alters cell-cell and cell-matrix adhesion dynamics, suggesting an important role for CHD1 in the development and progression of PCa.
Sex and ethnic differences in the cardiovascular complications of type 2 diabetes
Authors: Yeo Jian L. , Brady Emer M. , McCann Gerry P. , Gulsin Gaurav S.
Published: August 2021

Diabetes mellitus represents a global health concern affecting 463 million adults and is projected to rapidly rise to 700 million people by 2045. Amongst those with type 2 diabetes (T2D), there are recognised differences in the impact of the disease on different sex and ethnic groups. The relative risk of cardiovascular complications between individuals with and without T2D is higher in females than males. People of South Asian heritage are two to four times more likely to develop T2D than white people, but conversely not more likely to experience cardiovascular complications. Differences in the pathophysiological responses in these groups may identify potential areas for intervention beyond glycaemic control. In this review, we highlight key differences of diabetes-associated cardiovascular complications by sex and ethnic background, with a particular emphasis on South Asians. Evidence assessing therapeutic efficacy of new glucose lowering drugs in minority groups is limited and many major cardiovascular outcomes trials do not report ethnic specific data. Conversely, lifestyle intervention and bariatric surgery appear to have similar benefits regardless of sex and ethnic groups. We encourage future studies with better representation of women and ethnic minorities that will provide valuable data to allow better risk stratification and tailored prevention and management strategies to improve cardiovascular outcomes in T2D.
The (other) two percent also matter: The construction of mobile phone refusers
Authors: Rosenberg Hananel , Vogelman-Natan Kalia
Published: August 2021

Technological resistance practices hold significant insights regarding the media’s role as much as its adoption and usage practices. However, studies examining media non-use have generally overlooked mobile phone resisters—individuals voluntarily deciding not to own mobile phones. Based on 25 in-depth interviews with mobile phone refusers, this study presents two refuser types differing in refusal dynamics. The first are ideologists, whose rejection stems from a formulated, critical worldview towards the mobile phone, in particular, and communication technologies, in general. The second are realizers, whose “post-factum resistance” resulted from a forced but positive experience of a temporary break in use (e.g., when their device was broken or stolen), motivating them to disconnect in an attempt to preserve the new, liberated space they experienced. Additional findings reveal the non-ownership practices adopted by the mobile phone refusers; the novel psychological and sociological motives underlying mobile phone refusal concerning the home space and digital well-being; refuser resistance discourse, which focuses solely on the medium’s nature and not its content; and how refusers negotiate the social status and stigma that accompanies their mobile phone refusal. Our study illustrates how mobile phone refusal stands apart from other media resistance, providing a deeper perspective on the price of connectivity, and thus underscoring the importance of studying these refusers. The uniqueness of mobile phone refusal is further expressed in its complexity, extremity, perceived authenticity, and visibility.
Cognitive functioning in everyday life: The development of a questionnaire on instrumental activities of daily living in multiple sclerosis
Authors: van Dam Maureen , Sikkes Sietske AM , Rammeloo Emma , Reinders Evy , Jelgerhuis Julia R , Geurts Jeroen JG , Uitdehaag Bernhard MJ , Hulst Hanneke E
Published: August 2021

Neuropsychological test scores in people with MS (PwMS) do not fully reflect cognitive functioning in daily life. Therefore, we developed a questionnaire based on instrumental activities of daily living (IADL), using the Amsterdam IADL-Q© for Alzheimer’s disease as starting point. Forty-eight items were evaluated on relevance and clarity by (inter)national experts (n = 30), PwMS (n = 61) and proxies (n = 30). Consequently, four items were omitted, two items were merged and seven items were added. Fifty items were included in the IADL questionnaire specific to cognitive functioning in MS (the MS-IADL-Q). Future studies are warranted to assess the psychometric properties of the MS-IADL-Q.
Analysis of Ageism, Sexism, and Ableism in User Comments on YouTube Videos About Climate Activist Greta Thunberg
Authors: Park Chang Sup , Liu Qian , Kaye Barbara K.
Published: August 2021

This study content analyzed 3,300 user comments from the 11 most-viewed YouTube videos about climate activist Greta Thunberg. The analysis reveals that about 4 in 10 comments contained some form of incivility. Moreover, 40% of the uncivil comments reflected ageism, slightly more than one third sexism, and just less than one quarter ableism. The analysis suggests that uncivil comments about Thunberg on YouTube were far from deliberative in nature, ignored her positions on climate change altogether, and focused on her youth, gender, and Asperger’s syndrome.
Variation in criteria of examination grades from the perspective of “control rights” theory: An analysis of the grading of history as a subject in the new gaokao
Authors: Hu Yuehan
Published: August 2021

Existing literature on national governance models has focused on the analysis of long-term, stable public organizational processes between different levels of governmental and social organizations. In contemporary China, a considerable part of the organization and implementation process in public services relies on cooperation among different local governmental institutions and social groups. This type of process is characterized by short-termism and instability. This paper uses the perspective of the “control rights” theory to analyze the relationship between the three parties: the principal, management, and the implementation agency in the case of the phenomenon of grading criteria variation in the grading of history as a subject in the gaokao (college-entrance examination) of Province X. This paper shows that although the relationship shows a high degree of correlation, the three parties do not belong to the same bureaucratic organization and lack administrative oversight within the process, which increases the uncertainty in negotiation and maneuvering, resulting in two issues: First, the principal party and management party often have divergent views on targets. With the advantage of controlling incentive distribution, the principal party is able to involve itself in the inspection and evaluation of policy implementation, and therefore maintains the ability to arbitrarily intervene in the process. Second, implementation agency behavior is constantly influenced and modified by feedback from the principal party and the management party, and vice versa. In the process of continuous feedback and adjustment, the three parties gradually reach their own shared understanding of policy implementation that becomes the cause of local variation in grading standards. This paper suggests that unstable public organization process is an important area of study on contemporary Chinese governance. Control rights theory can be further explored as an analytic tool and strategies of various social forces in gaining organizational control should also be investigated in depth.
Pulmonary ventilation reserve function is used to predict intraoperative ventilation function and postoperative outcome in patients with spinal orthopedic surgery
Authors: Yu Mingshuai , Zhang Ke , Qi Lei , Liu Siyuan
Published: August 2021

Objective

To investigate the effect of pulmonary ventilation reserve function on perioperative pulmonary function and postoperative outcome in patients undergoing spinal orthopedic surgery.

Methods

Ninety patients undergoing spinal orthopedic surgery in our hospital from June 2019 to December 2020 were divided into two groups according to the percentage of preoperative pulmonary reserve function index MVV in the predicted value. Arterial oxygen partial pressure, carbon dioxide partial pressure, oxygenation index (OI), airway plateau pressure (Pplat), and airway resistance (AR) of patients in each group were observed before the start of surgery (T0), at 1 h (T1) and 2 h (T2) after the start of surgery, and at the end of surgery (T3). After the end of surgery, the probability of patient transfer to ICU, time to resume spontaneous breathing, and time to extubation were recorded, and PaO2 and inflammatory factors interleukin-6, procalcitonin, and C-reactive protein of patients were followed up for 1 week.

Results

In both groups, PaO2 and OI decreased obviously while Pplat and AR increased significantly at T1, T2, and T3, but in Group A, Pplat and AR were markedly lower than those in Group B while PaO2 and OI were notably higher than those in Group B ( p < 0.05). Both time to resume spontaneous breathing and time to extubation in Group B were longer than those in Group A ( p < 0.05). The probability of entering ICU in Group B is higher than that in Group A. Both PaO2 and OI at day 3 after surgery in Group B were lower than those in Group A. While, there is no difference at T2.

Conclusion

For patients, both intraoperative pulmonary function and time to postoperative resuscitation can be predicted by measuring the preoperative MVV, and long-term prognosis will not be affected by the pulmonary function impairment.
Does Superior Bone Health Promote a Longer Lifespan?
Authors: Dayer Stephanie R. , Mears Simon C. , Pangle Amanda K. , Mendiratta Priya , Wei Jeanne Y. , Azhar Gohar
Published: August 2021

Introduction

Public health achievements throughout the last century have resulted in a steady increase in life expectancy. An emergent subset has distinguished themselves, living well beyond the ninth decade by avoiding or delaying the onset of most age-related diseases, including bone diseases and fractures. In this study, we evaluated the bone health of the oldest community-dwelling individuals living in rural Arkansas.

Methods

299 patients aged ≥90 years were retrospectively reviewed for recorded fractures within 12 years prior to the investigation period. Records were also examined for medications and test results pertinent to bone health, including thyroid stimulating hormone, vitamin D levels, hematocrit, hemoglobin, body mass index, and bone densitometric values.

Results

68 patients (23%) had at least one fracture documented, and 15 had >1 fracture. 40% of patients with fractures had osteoporosis and 28% had osteopenia, respectively. 232 patients (78%) had no documented fractures, and of these, only 18% had osteoporosis and 16% had osteopenia. No significant clinical markers were found among the very old to explain the relatively low occurrence of fractures.

Conclusions

Patients over 90 years of age had an overall low prevalence of fractures and relative preservation of bone health, suggesting a preserved bone molecular profile in these individuals. Epigenetic factors and activity levels might also have favorably affected bone health. The low percentage of osteoporosis and fractures likely reduced the morbidity and mortality in this population, potentially contributing to their overall longevity.
A Case of Guillain-Barré Syndrome and Stevens-Johnson Syndrome/Toxic Epidermal Necrosis Overlap After Pembrolizumab Treatment
Authors: Oguri Tomoyo , Sasada Shinji , Shimizu Satoko , Shigematsu Risa , Tsuchiya Yumi , Ishioka Kota , Takahashi Saeko , Oki Koichi , Kimura Yoshifumi , Seki Reishi , Hirose Shigemichi , Nakamura Morio
Published: August 2021

A 76-year-old man was admitted to our hospital with Guillain-Barré syndrome (GBS), presenting with facial palsy, dysarthria, and dysphagia as Grade 3 immune-related adverse events (irAEs) due to pembrolizumab administration for Stage IV lung adenocarcinoma. Although prednisolone (1 mg/kg) was started for GBS due to the irAE, dark erythema and skin eruptions appeared on the patient’s torso. Then erosion was observed on 18% of the body surface area and skin biopsy was performed. Finally, the patient was diagnosed with Stevens-Johnson syndrome/toxic epidermal necrosis overlap. Intravenous immunoglobulin therapy was started, and the skin symptoms improved, with the erosion becoming epithelial. He died of aspiration pneumonia related to GBS, although his neurological symptoms had improved after steroid and intravenous immunoglobulin therapy. This is the first reported case of pembrolizumab-induced GBS and Stevens–Johnson syndrome/toxic epidermal necrosis overlap. It is necessary to be careful that the possibility of other severe irAEs may occur simultaneously.
Teacher Knowledge in Transition Planning: Does Locale Matter?
Authors: Deardorff Malarie E. , Peltier Corey , Choiseul-Praslin Belkis , Williams-Diehm Kendra , Wicker Melissa
Published: August 2021

The Individuals With Disabilities Education Act mandates transition planning to occur in conjunction with the individualized education program for secondary age students with disabilities beginning by age 16, or earlier. To fulfill this mandate, teachers must possess a depth of content and pedagogical knowledge related to the transition planning process. However, the majority of special educators do not receive coursework dedicated to transition in their undergraduate programming. Furthermore, teachers in under-resourced and underserved rural districts may have inequitable professional development opportunities to bolster their transition planning knowledge. This lack of transition-related education potentially leads to inadequate and noncompliant transition plans for students with disabilities. The current study examined differences in teachers’ knowledge based on locale: rural ( n = 75), suburban ( n = 48), and urban ( n = 64) from one southern state. Determining whether differences are identified by locale can inform the allocation of resources to provide high-quality, evidence-aligned professional development models to improve teacher knowledge in underserved and under-resourced rural locales. In addition, identifying gaps in teacher knowledge will inform pre-service and in-service teacher preparation. We provide an avenue of needed future research to improve transition-planning processes for students with disabilities.
Airway granulation response to lung-implantable medical devices: a concise overview
Authors: Roodenburg Sharyn A. , Pouwels Simon D. , Slebos Dirk-Jan
Published: August 2021

Increasing numbers of endoscopically implantable devices are implanted in the airways, such as airway stents, one-way valves and coils, to treat both malignant and benign diseases. They significantly improve patient outcomes, but their long-term effectiveness and sustainability is hampered by the reaction of the formation of granulation tissue. Factors including procedural-related tissue injury; micro-organism presence; device-related factors, such as the material, design and sizing in relation to the airway; and patient-related factors, including genetic susceptibility, comorbidities and medication use, might all effect the severity of the tissue response and the subsequent degree of granulation tissue formation. However, research into the underlying mechanism and risk factors is scarce and therefore our knowledge is limited. Joint efforts from the scientific community, both pre-clinical and clinical, are needed to gain a deeper understanding and eventually improve the long-term treatment effectiveness of lung-implantable devices.
A scoping review of palliative care outcome measures in interstitial lung disease
Authors: Gersten Rebecca A. , Moale Amanda C. , Seth Bhavna , Vick Judith B. , Brown Hannah , Eakin Michelle N. , Mathai Stephen C. , Danoff Sonye K.
Published: August 2021

Interstitial lung disease (ILD) confers a high mortality and symptom burden, substantially impacting quality of life. Studies evaluating palliative care in ILD are rapidly expanding. Uniform outcome measures are crucial to assessing the impact of palliative care in ILD. This scoping review evaluates existing outcome measures in general health-related quality of life (HRQoL), physical health, mental health, social health and advance care planning (ACP) domains in patients with ILD. Articles in English with quantitative assessment of at least one measure of general HRQoL, physical health, mental health, social health or ACP in patients with ILD were included. Searches across three databases yielded 3488 non-duplicate articles. 23 met eligibility criteria and included three randomised controlled trials (RCTs) or secondary analysis of an RCT (13%), three cross-sectional studies or secondary analysis of cross-sectional study (13%), one prospective study (4%) and 16 retrospective studies (70%). Among eligible articles, 25 distinct instruments were identified. Six studies assessed general HRQoL (26%), 16 assessed physical health (70%), 11 assessed mental health (48%), six assessed social health (26%) and 16 assessed ACP (70%). The ability to compare results across studies remains challenging given the heterogeneity in outcome measures. Future work is needed to develop core palliative care outcome measures in ILD.
Tuberous sclerosis complex for the pulmonologist
Authors: Rebaine Yasmine , Nasser Mouhamad , Girerd Barbara , Leroux Caroline , Cottin Vincent
Published: August 2021

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder affecting almost all organs with no sex predominance. TSC has an autosomal-dominant inheritance and is caused by a heterozygous mutation in either theTSC1orTSC2gene leading to hyperactivation of the mammalian target of rapamycin (mTOR). TSC is associated with several pulmonary manifestations including lymphangioleiomyomatosis (LAM), multifocal micronodular pneumocyte hyperplasia (MMPH) and chylous effusions. LAM is a multisystem disorder characterised by cystic destruction of lung parenchyma, and may occur in either the setting of TSC (TSC-LAM) or sporadically (S-LAM). LAM occurs in 30–40% of adult females with TSC at childbearing age and is considered a nonmalignant metastatic neoplasm of unknown origin. TSC-LAM is generally milder and, unlike S-LAM, may occur in males. It manifests as multiple, bilateral, diffuse and thin-walled cysts with normal intervening lung parenchyma on chest computed tomography. LAM is complicated by spontaneous pneumothoraces in up to 70% of patients, with a high recurrence rate. mTOR inhibitors are the treatment of choice for LAM with moderately impaired lung function or chylous effusion. MMPH, manifesting as multiple solid and ground-glass nodules on high-resolution computed tomography, is usually harmless with no need for treatment.
Parameters affecting baseline hip function in patients with cam-derived femoroacetabular impingement syndrome: data analysis from the German Cartilage Registry
Authors: Serong Sebastian , Schutzbach Moritz , Fickert Stefan , Niemeyer Philipp , Sobau Christian , Spahn Gunther , Zinser Wolfgang , Landgraeber Stefan
Published: August 2021

Background

Using the database of the German Cartilage Registry (KnorpelRegister DGOU), this study aims to present patient- and joint-related baseline data in a large cohort of patients with cam-derived femoroacetabular impingement syndrome (FAI) and to detect symptom-determining factors.

Materials and methods

Requiring cam morphology as the primary pathology, 362 patients were found to be eligible for inclusion in the study. The assessment of preoperative baseline data was performed using the patient-reported outcome measure—International Hip Outcome Tool (iHOT-33). Descriptive statistics were performed to present baseline data. Univariate and multiple regression with post hoc testing were used to identify patient- and joint-related factors that might affect the preoperative iHOT-33 and its subscores, respectively.

Results

The study collective’s mean age was 36.71 ± 10.89 years, with 246 (68%) of them being male. The preoperative mean iHOT-33 total was 46.31 ± 20.33 with the subsection “sports and recreational activities” presenting the strongest decline (26.49 ± 20.68). The parameters “age,” “sex,” “body mass index” (BMI), and the confirmation of “previous surgery on the affected hip” were identified to statistically affect the preoperative iHOT-33. In fact, a significantly lower mean baseline score was found in patients aged > 40 years (p < 0.001), female sex (p < 0.001), BMI ≥ 25 kg/m2 (p = 0.002) and in patients with previous surgery on the affected hip (p = 0.022). In contrast, the parameters defect grade and size, labral tears, and symptom duration delivered no significant results.

Conclusions

A distinct reduction in the baseline iHOT-33, with mean total scores being more than halved, was revealed. The parameters “age > 40 years,” “female sex,” “BMI ≥ 25,” and confirmation of “previous surgery on the affected hip” were detected as significantly associated with decreased preoperative iHOT-33 scores. These results help to identify symptom-defining baseline characteristics of cam-derived FAI syndrome.

Trial registration: The German Cartilage Registry is conducted in accordance with the Declaration of Helsinki and registered at germanctr.de (DRKS00005617). Registered 3 January 2014—retrospectively registered. The registration of data was approved by the local ethics committees of every participating institution. Primary approval was given by the ethics committee at the University of Freiburg (No. 105/13). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00005617
Construction and characterization of EGFP reporter plasmid harboring putative human RAX promoter for in vitro monitoring of retinal progenitor cells identity
Authors: Atefi Atefeh , Kojouri Pendar Shojaei , Karamali Fereshteh , Irani Shiva , Nasr-Esfahani Mohammad Hossein
Published: August 2021

Background

In retinal degenerative disease, progressive and debilitating conditions result in deterioration of retinal cells and visual loss. In human, retina lacks the inherent capacity for regeneration. Therefore, regeneration of retinal layer from human retinal progenitor cells (hRPCs) is a challenging task and restricted in vitro maintenance of hRPCs remains as the main hurdle. Retina and anterior neural fold homeobox gene (RAX) play critical roles in developing retina and maintenance of hRPCs. In this study, for the first time regulatory regions of human RAX gene with potential promoter activity were experimentally investigated.

Results

For this purpose, after in silico analysis of regulatory regions of human RAX gene, the expression of EGFP reporter derived by putative promoter sequences was first evaluated in 293 T cells and then in hRPCS derived from human embryonic stem cells. The candidate region (RAX-3258 bp) showed the highest EGFP expression in hRPCs. This reporter construct can be used for in vitro monitoring of hRPC identity and verification of an efficient culture medium for maintenance of these cells.

Conclusions

Furthermore, our findings provide a platform for better insight into regulatory regions of human RAX gene and molecular mechanisms underlying its vital functions in retina development.
Apicidin biosynthesis is linked to accessory chromosomes in Fusarium poae isolates
Authors: Witte Thomas E. , Harris Linda J. , Nguyen Hai D. T. , Hermans Anne , Johnston Anne , Sproule Amanda , Dettman Jeremy R. , Boddy Christopher N. , Overy David P.
Published: August 2021

Background

Fusarium head blight is a disease of global concern that reduces crop yields and renders grains unfit for consumption due to mycotoxin contamination.Fusarium poaeis frequently associated with cereal crops showing symptoms of Fusarium head blight. While previous studies have shownF. poaeisolates produce a range of known mycotoxins, including type A and B trichothecenes, fusarins and beauvericin, genomic analysis suggests that this species may have lineage-specific accessory chromosomes with secondary metabolite biosynthetic gene clusters awaiting description.

Methods

We examined the biosynthetic potential of 38 F. poaeisolates from Eastern Canada using a combination of long-read and short-read genome sequencing and untargeted, high resolution mass spectrometry metabolome analysis of extracts from isolates cultured in multiple media conditions.

Results

A high-quality assembly of isolate DAOMC 252244 (Fp157) contained four core chromosomes as well as seven additional contigs with traits associated with accessory chromosomes. One of the predicted accessory contigs harbours a functional biosynthetic gene cluster containing homologs of all genes associated with the production of apicidins. Metabolomic and genomic analyses confirm apicidins are produced in 4 of the 38 isolates investigated and genomic PCR screening detected the apicidin synthetase geneAPS1in approximately 7% of Eastern Canadian isolates surveyed.

Conclusions

Apicidin biosynthesis is linked to isolate-specific putative accessory chromosomes inF. poae. The data produced here are an important resource for furthering our understanding of accessory chromosome evolution and the biosynthetic potential ofF. poae.
Genome-wide CNV investigation suggests a role for cadherin, Wnt, and p53 pathways in primary open-angle glaucoma
Authors: Lo Faro Valeria , ten Brink Jacoline B. , Snieder Harold , Jansonius Nomdo M. , Bergen Arthur A.
Published: August 2021

Background

To investigate whether copy number variations (CNVs) are implicated in molecular mechanisms underlying primary open-angle glaucoma (POAG), we used genotype data of POAG individuals and healthy controls from two case-control studies, AGS (n = 278) and GLGS-UGLI (n = 1292). PennCNV, QuantiSNP, and cnvPartition programs were used to detect CNV. Stringent quality controls at both sample and marker levels were applied. The identified CNVs were intersected in CNV region (CNVR). After, we performed burden analysis, CNV-genome-wide association analysis, gene set overrepresentation and pathway analysis. In addition, in human eye tissues we assessed the expression of the genes lying within significant CNVRs.

Results

We reported a statistically significant greater burden of CNVs in POAG cases compared to controls (p-value = 0,007). In common between the two cohorts, CNV-association analysis identified statistically significant CNVRs associated with POAG that span 11 genes (APC, BRCA2, COL3A1, HLA-DRB1, HLA-DRB5, HLA-DRB6, MFSD8, NIPBL, SCN1A, SDHB, and ZDHHC11). Functional annotation and pathway analysis suggested the involvement of cadherin, Wnt signalling, and p53 pathways.

Conclusions

Our data suggest that CNVs may have a role in the susceptibility of POAG and they can reveal more information on the mechanism behind this disease. Additional genetic and functional studies are warranted to ascertain the contribution of CNVs in POAG.
Stressor controllability modulates the stress response in fish
Authors: Cerqueira Marco , Millot Sandie , Silva Tomé , Félix Ana S. , Castanheira Maria Filipa , Rey Sonia , MacKenzie Simon , Oliveira Gonçalo A. , Oliveira Catarina C. V. , Oliveira Rui F.
Published: August 2021

Background

In humans the stress response is known to be modulated to a great extent by psychological factors, particularly by the predictability and the perceived control that the subject has of the stressor. This psychological dimension of the stress response has also been demonstrated in animals phylogenetically closer to humans (i.e. mammals). However, its occurrence in fish, which represent a divergent vertebrate evolutionary lineage from that of mammals, has not been established yet, and, if present, would indicate a deep evolutionary origin of these mechanisms across vertebrates. Moreover, the fact that psychological modulation of stress is implemented in mammals by a brain cortical top-down inhibitory control over subcortical stress-responsive structures, and the absence of a brain cortex in fish, has been used as an argument against the possibility of psychological stress in fish, with implications for the assessment of fish sentience and welfare. Here, we have investigated the occurrence of psychological stress in fish by assessing how stressor controllability modulates the stress response in European seabass (Dicentrarchus labrax).

Results

Fish were exposed to either a controllable or an uncontrollable stressor (i.e. possibility or impossibility to escape a signaled stressor). The effect of loss of control (possibility to escape followed by impossibility to escape) was also assessed. Both behavioral and circulating cortisol data indicates that the perception of control reduces the response to the stressor, when compared to the uncontrollable situation. Losing control had the most detrimental effect. The brain activity of the teleost homologues to the sensory cortex (Dld) and hippocampus (Dlv) parallels the uncontrolled and loss of control stressors, respectively, whereas the activity of the lateral septum (Vv) homologue responds in different ways depending on the gene marker of brain activity used.

Conclusions

These results suggest the psychological modulation of the stress response to be evolutionary conserved across vertebrates, despite being implemented by different brain circuits in mammals (pre-frontal cortex) and fish (Dld-Dlv).
The prevalence, relative risk factors and MTHFR C677T genotype of H type hypertension of the elderly hypertensives in Shanghai, China: a cross-section study
Authors: Qian Xiao-lin , Cao Hong , Zhang Jun , Gu Zhi-hui , Tang Wei-qin , Shen Lei , Hu Jia-lu , Yao Zhi-feng , Zhang Lei , Tang Min-na , Lv Xu-cheng , Zhou Jun , Jin Xue-juan , Hong Bin , Cui Zhao-qiang , Ge Jun-bo
Published: August 2021

Background

H type hypertension is defined as homocysteine (Hcy) ≥ 10 μmol/L in combination with primary hypertension. Studies demonstrated that the existence of hyperhomocysteine (HHcy) in hypertensive exacerbates the poor outcome of cardiocerebral incidents. This study was to investigate the current epidemic situation of H type hypertension and determine the risk factors in order to find intervention targets for H type hypertensives.

Methods

We conducted a cross-sectional study using cluster sampling design in Shanghai, China from July 2019 and April 2020. 23,652 patients with primary hypertension were enrolled in this study. Their medical information was recorded, and the level of Hcy concentrations and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms were detected.

Results

In total, 22,731 of 23,652 patients were recorded. The mean age was 68.9 ± 8.6 y and 43% were men. 80.0% of the enrolled patients had H type hypertension. The frequency of allele T was 40.9%, and the proportions of the CC, CT, and TT genotypes were 36.1%, 46.0%, and 17.9%, respectively. Compared with the TT genotype, the plasma Hcy concentration levels were lower in patients with the CC/CT genotype (18.96 ± 13.48 μmol/L vs. 13.62 ± 5.20/14.28 ± 5.36, F = 75.04, p < 0.01). The risk for H type hypertension was higher in elderly people. Men had ~ 5.55-fold odds of H type hypertension compared with women. Patients with CT genotype and TT genotype had ~ 1.36- and ~ 2.76-fold odds of H type hypertension compared with those with CC genotype, respectively. Smoking and diabetes were not significantly associated with H type hypertension.

Conclusions

The prevalence of H type hypertension in patients with primary hypertension was 80.0%, which was higher than the 75% found in prior report in China. Age, gender, and MTHFR C677T polymorphisms rather than smoking and diabetes were independently associated with H type hypertension.
The elevated expression of TLR4 and MMP9 in human abdominal aortic aneurysm tissues and its implication
Authors: Li Tan , Li Xintong , Liu Xiaozheng , Yang Jun , Ma Chunyan
Published: August 2021

Background

Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) have been investigated to play significant roles in the formation of abdominal aortic aneurysm (AAA). But the reports on the expression pattern of TLR4 and MMP9 in human AAA specimens were relatively scant. The aim of this study was to make a detailed analysis of TLR4 and MMP9 expression in situ and their association with clinical parameters involved in human AAA.

Methods

40 AAA specimens were obtained from full-thickness aneurysmal tissues at the maximal dilation area during the open surgical repair, and 8 non-aneurysmal abdominal aortas from transplant donors served as controls. Expression of TLR4 and MMP9 protein was determined by immunohistochemistry.

Results

There were increased levels of TLR4 and MMP9 expression in human AAA tissues. Compared with macrophages or SMCs, lymphocytes showed a higher positive rate of TLR4 and MMP9 staining, and an elevated ratio of high MMP9 expression (allP < 0.05). There existed a significant association between TLR4 and MMP9 expression (r = 0.767,P < 0.001), and both TLR4 and MMP9 levels were statistically related to circulating CRP. Moreover, TLR4 expression in situ indicated a positive correlation with its serum level (r = 0.654,P = 0.006). Multiple analysis revealed that high TLR4 expression in situ was associated with the risk of large AAA (OR = 6.211, 95%CI = 1.226–31.480,P = 0.027), while high MMP9 expression was correlated to the presence of thrombus within AAA (OR = 5.494, 95%CI = 1.181–25.562,P = 0.030), separately compared with their low expression.

Conclusions

This study confirmed the overexpression of TLR4 and MMP9 in human AAA tissues, and their close relationship implying in the pathogenesis of AAA. We further provided evidence that TLR4 had a potential effect on AAA size and MMP9 could influence the occurrence of thrombus within AAA.
Prevalence of strongyloidiasis in Peru: systematic review and meta-analysis
Authors: Ortiz-Martínez Sonia , Ramos-Rincón José-Manuel , Vásquez-Chasnamote María-Esteyner , Gamboa-Paredes Olga-Nohelia , Arista-Flores Katty-Madeleine , Espinoza-Venegas Luis-Alfredo , de-Miguel-Balsa Eva , Pinedo-Cancino Viviana-Vanessa , Górgolas-Hernández-Mora Miguel , Casapía-Morales Martín
Published: August 2021

Background

Strongyloidiasis is a disease of great public health significance, caused by the parasitic nematodesStrongyloides stercoralis,Strongyloides fuelleborni, andStrongyloides fuellebornisubsp. kellyi. This systematic review and meta-analysis aimed to assess the prevalence ofStrongyloides stercoralisinfection in Peru.

Methods

The review was based on a literature search in PubMed, SciELO and Google Scholar using the key words or root words “strongyl*” AND “Peru” on 15 July 2020. Eligible studies were published from 1 January 1981 to 15 July 2020 and written in English, Spanish, Italian, or French.

Results

We included 21 papers in the analysis. Studies were heterogeneous in terms of study population and diagnostic methods (e.g. Baermann technique, agar, Dancescu or charcoal cultures, serology, string capsule). Prevalence ofS. stercoralisranged from 0.3 to 45%. The pooled proportion ofStrongyloidesin the general population was 7.34% (95% CI 4.97 to 10.13%). Half the studies were designed to detect parasites in general. In studies designed to detectS. stercoralis, the most widely used diagnostic method was the Baermann technique.

Conclusion

Prevalence ofS. stercoralisin Peru was high but varied by geographic area, techniques for stool examination, and participant characteristics.
The role of trust and hope in antipsychotic medication reviews between GPs and service users a realist review
Authors: Grünwald L. M. , Duddy C. , Byng R. , Crellin N. , Moncrieff J.
Published: August 2021

Background

Increasing number of service users diagnosed with schizophrenia and psychosis are being discharged from specialist secondary care services to primary care, many of whom are prescribed long-term antipsychotics. It is unclear if General Practitioners (GPs) have the confidence and experience to appropriately review and adjust doses of antipsychotic medication without secondary care support.

Aim

To explore barriers and facilitators of conducting antipsychotic medication reviews in primary care for individuals with no specialist mental health input.

Design & setting

Realist review in general practice settings.

Method

A realist review has been conducted to synthesise evidence on antipsychotic medication reviews conducted in primary care with service users diagnosed with schizophrenia or psychosis. Following initial scoping searches and discussions with stakeholders, a systematic search and iterative secondary searches were conducted. Articles were systematically screened and analysed to develop a realist programme theory explaining the contexts (C) and mechanisms (M) which facilitate or prevent antipsychotic medication reviews (O) in primary care settings, and the potential outcomes of medication reviews.

Results

Meaningful Antipsychotic medication reviews may not occur for individuals with only primary care medical input. Several, often mutually reinforcing, mechanisms have been identified as potential barriers to conducting such reviews, including low expectations of recovery for people with severe mental illness, a perceived lack of capability to understand and participate in medication reviews, linked with a lack of information shared in appointments between GPs and Service Users, perceived risk and uncertainty regarding antipsychotic medication and illness trajectory.

Conclusions

The review identified reciprocal and reinforcing stereotypes affecting both GPs and service users. Possible mechanisms to counteract these barriers are discussed, including realistic expectations of medication, and the need for increased information sharing and trust between GPs and service users.
Severe diaphoresis and fever during alcohol withdrawal cause hypovolemic shock: case report
Authors: Funayama Michitaka , Okochi Ryotaro , Asada Shintaro , Shimizu Yusuke , Kurose Shin , Takata Taketo
Published: August 2021

Background

Several fatal medical complications have been associated with alcohol withdrawal, such as seizure, cardiac arrhythmia, and takotsubo cardiomyopathy. However, there have been no reports on hypovolemic shock during alcohol withdrawal, although two physical signs of alcohol withdrawal, i.e., diaphoresis and fever, can lead to hypovolemia and its medical consequences.

Case presentation

We describe a patient with alcohol use disorder who exhibited hypovolemic shock and its associated acute renal failure during alcohol withdrawal with severe diaphoresis and fever even though he had consumed almost the full amount of food he was offered. Given his excessive diaphoresis and fever that were related to alcohol withdrawal, his water intake was insufficient. Infusion with extracellular fluid resolved all these medical issues.

Conclusions

The increased adrenergic activity associated with alcohol withdrawal might substantially increase a patient’s water-intake requirement through diaphoresis and fever and may cause severe hypovolemia and its associated medical complications.