bluuebunny/crossref_metadata_2025 huggingface dataset:
A framework exploring the therapeutic alliance between elite athletes and physiotherapists: a qualitative study
Authors: Charmant W. M. , van der Wees P. J. , Staal J. B. , van Cingel R. , Sieben J. M. , de Bie R. A.
Published: October 2021

Background

The therapeutic alliance (TA) is the bond between a patient and a physiotherapist during collaboration on recovery or training. Previous studies focused on the TA between physiotherapists and patients of the general population. Little information exists on whether this is similar in the demanding environment of elite athletes. The aim of this study was to investigate the components of TA between elite athletes and physiotherapists.

Methods

Ten elite athletes and ten physiotherapists were interviewed using one-on-one semi-structured interviews between June 2020 and October 2020. Athletes were included if they competed at national or international championships. Physiotherapists had to treat elite athletes on a regular basis. Interview questions were based on TA components of the general physiotherapy population. The interviews were transcribed and coded using inductive thematic analysis.

Results

The analysis resulted in an elite athlete TA framework which consists of nine themes and ten subthemes that could influence the TA. The nine themes are trust, communication, professional bond, social bond, elite athlete, physiotherapist, time, pressure and adversity, and external factors. This showed that the TA consists of bonds on different social levels, depends on the traits of both elite athletes and physiotherapists, and can be positively and negatively influenced by the external environment. The influences from the external environment seem to be more present in the elite athlete TA compared to the TA in the general physiotherapy setting. Multiple relations between themes were discovered. Trust is regarded as the main connecting theme.

Conclusion

This study provides a framework to better understand the complex reality of the TA between elite athletes and physiotherapists. Compared to the general physiotherapy setting, new themes emerged. The created framework can help elite athletes and physiotherapists to reflect and improve their TA and subsequently improve treatment outcomes.
Engaging people with long-term health conditions in a community-based physical activity initiative: a qualitative follow-up study evaluating the parkrun PROVE project
Authors: Quirk Helen , Haake Steve
Published: October 2021

Background

The “parkrun: running or volunteering for everyone” (PROVE) project was an example of a community-based physical activity and volunteering initiative for people living with long-term health conditions in England. The 3 year project involved appointing volunteer Outreach Ambassadors whose role was to promote parkrun to people living with long-term health conditions through various outreach activities. This qualitative study aimed to understand the experience of delivering the project from the perspective of volunteer Outreach Ambassadors and the PROVE Project Manager.

Methods

The PROVE Project Manager and ten PROVE Outreach Ambassadors across nine health condition groups were interviewed by the researcher (asthma, blood pressure, deaf and hard of hearing, dementia, diabetes, endometriosis, heart conditions, learning disabilities and/or autism, and obesity). Interview transcripts were analysed using thematic analysis.

Results

Four themes and nine sub-themes were generated. The participants highlighted challenges in measuring the project’s success and bringing about meaningful and lasting change, and reflected on the value of the project as a learning opportunity. Despite some successes, it was thought that the project had limited reach outside of the existing parkrun community. The Outreach Ambassadors reflected on their experiences in the role and the skills required, finding it rewarding and highlighting the importance of networking and forming connections with key stakeholders. The findings are discussed in comparison to interviews conducted with the Outreach Ambassadors 12 months earlier.

Conclusions

This study provides evidence to support the public health potential of parkrun though targeted initiatives such as the PROVE project and provides a critical reflection on what worked and what did not work when delivering the project. The findings have relevance for organisations wishing to implement similar outreach initiatives using a volunteer workforce, including recommendations for resource management, communication, leadership, fostering volunteer autonomy and defining and capturing success.
Effects of nail softness and stiffness with distance running shoes on ground reaction forces and vertical loading rates in male elite long-distance runners with pronated feet
Authors: Jafarnezhadgero Amir Ali , Fakhri Ehsan , Granacher Urs
Published: October 2021

Background

To improve propulsion during running, athletes often wear spike shoes designed for training and/or competition. Running with spike shoes may cause pain and/or injuries. To address this problem, a modified spike shoe was tested. This study aimed to evaluate the effects of running with dual-versus single-stiffness spike running shoes on running mechanics in long-distance runners with pronated feet.

Methods

Sixteen male elite (national competitive level) runners (5000 or 10,000 m) aged 28.2 ± 2.5 years with pronated feet volunteered to participate in this study. To be included, participants had to have achieved personal best race times over 5- and/or 10-km races under 17 or 34 min during official running competitions. All participants were heel strikers and had a history of 11.2 ± 4.2 years of training. For the assessment of running kinetics, a force plate was imbedded into a walkway. Running kinematics were recorded using a Vicon-motion-capture system. Nike Zoom Rival shoes (Nike, Nike Zoom Rival, USA) were selected and adapted according to spike softness and stiffness. Participants ran at a constant speed of ~4.0 m/s across the walkway with both shoe conditions in randomized order. Six trials were recorded per condition. The main outcomes included peak ground reaction forces and their time-to-peak, average and instantaneous vertical loading rates, free moments, and peak ankle eversion angles.

Results

Paired t-tests revealed significantly lower lateral (p = 0.021, d = 0.95) and vertical (p = 0.010, d = 1.40) forces at heel contact during running with dual-stiffness spike shoes. Running with dual-stiffness spike shoes resulted in a significantly longer time-to-peak vertical (p = 0.004, d = 1.40) force at heel contact. The analysis revealed significantly lower average (p = 0.005, d = 0.46) and instantaneous (p = 0.021, d = 0.49) loading rates and peak negative free moment amplitudes (p = 0.016, d = 0.81) when running with dual-stiffness spike shoes. Finally, significantly lower peak ankle eversion angles were observed with dual-stiffness spike shoes (p < 0.001, d = 1.29).

Conclusions

Running in dual- compared with single-stiffness spike distance running shoes resulted in lower loading rates, free moment amplitudes, and peak ankle eversion angles of long-distance runners with pronated feet.
Deactivation of the dorsal anterior cingulate cortex indicated low postoperative sports levels in presurgical patients with chronic ankle instability
Authors: Xue Xiao’ao , Li Shengkun , Li Hongyun , Li Qianru , Hua Yinghui
Published: October 2021

Background

Injury-related fear contributed to disability in chronic ankle instability (CAI), while there still lacked exploration on the appraisal processes of the injury-related stimuli. This study aimed to compare the neural activities of the appraisal processes of sprain-related stimuli between presurgical chronic ankle instability patients and healthy controls through functional magnetic resonance imaging (fMRI) and evaluate its relationships with the clinical outcomes of orthopedic surgeries.

Methods

Eighteen presurgical CAI patients and fourteen healthy controls were recruited and underwent an fMRI session with visual stimulation of movies that showing typical ankle sprains accidents or control videos and the corresponding fear ratings. The clinical outcomes were collected at baseline and a minimum of 2 years after surgery; these included the American Orthopaedic Foot and Ankle Society (AOFAS) scores, the Numeric Rating Scale (NRS) scores, and the Tegner Activity Rating Scale scores. The two-sample t-test would be applied to identify which brain regions were influenced by CAI, and the correlation analysis would be applied to measure the relationship between the activation and clinical outcomes.

Results

Dorsal anterior cingulate cortex (dACC) was deactivated in CAI patients when compared with healthy controls, and the dACC deactivation strength revealed a moderate correlation with the values of fear ratings for all participants. The deactivation strength was negatively correlated with AOFAS at baseline, with Tegner at follow-up and its improvement.

Conclusions

Presurgical CAI patients presented deactivated dACC as a different neural activity of appraisal processes of sprain-related stimuli when compared with healthy controls, which was associated with lower postoperative sports levels. More comprehensive patients care including psychological interventions were needed in the clinical management of chronic ankle instability.
DNA methylation signatures of incident coronary heart disease: findings from epigenome-wide association studies
Authors: Xia Yujing , Brewer Alison , Bell Jordana T.
Published: October 2021

Coronary heart disease (CHD) is a type of cardiovascular disease (CVD) that affects the coronary arteries, which provide oxygenated blood to the heart. It is a major cause of mortality worldwide. Various prediction methods have been developed to assess the likelihood of developing CHD, including those based on clinical features and genetic variation. Recent epigenome-wide studies have identified DNA methylation signatures associated with the development of CHD, indicating that DNA methylation may play a role in predicting future CHD. This narrative review summarises recent findings from DNA methylation studies of incident CHD (iCHD) events from epigenome-wide association studies (EWASs). The results suggest that DNA methylation signatures may identify new mechanisms involved in CHD progression and could prove a useful adjunct for the prediction of future CHD.
Visuospatial memory impairment as a potential neurocognitive marker to predict tau pathology in Alzheimer’s continuum
Authors: Seo Eun Hyun , Lim Ho Jae , Yoon Hyung-Jun , Choi Kyu Yeong , Lee Jang Jae , Park Jun Young , Choi Seong Hye , Kim Hoowon , Kim Byeong C. , Lee Kun Ho
Published: October 2021

Background

Given that tau accumulation, not amyloid-β (Aβ) burden, is more closely connected with cognitive impairment in Alzheimer’s disease (AD), a detailed understanding of the tau-related characteristics of cognitive function is critical in both clinical and research settings. We investigated the association between phosphorylated tau (p-Tau) level and cognitive impairment across the AD continuum and the mediating role of medial temporal lobe (MTL) atrophy. We also developed a prediction model for abnormal tau accumulation.

Methods

We included participants from the Gwangju Alzheimer’s Disease and Related Dementia Cohort in Korea, who completed cerebrospinal fluid analysis and clinical evaluation, and corresponded to one of three groups according to the biomarkers of A and T profiles based on the National Institute on Aging and Alzheimer’s Association research framework. Multiple linear and logistic regression analyses were performed to examine the association between p-Tau and cognition and to develop prediction models. Receiver operating characteristic curve analysis was performed to examine the discrimination ability of the models.

Results

Among 185 participants, 93 were classified as A-T-, 23 as A+T-, and 69 as A+T+. There was an association between decreased visuospatial delayed memory performance and p-Tau level (B = − 0.754, β = − 0.363, p < 0.001), independent of other relevant variables (e.g., Aβ). MTL neurodegeneration was found to mediate the association between the two. Prediction models with visuospatial delayed memory alone (area under the curve [AUC] = 0.872) and visuospatial delayed memory and entorhinal thickness (AUC = 0.921) for abnormal tau accumulation were suggested and they were validated in an independent sample (AUC = 0.879 and 0.891, respectively).

Conclusion

It is crucial to identify sensitive cognitive measures that capture subtle cognitive impairment associated with underlying pathological changes. Preliminary findings from the current study might suggest that abnormal tau accumulation underlies episodic memory impairment, particularly visuospatial modality, in the AD continuum. Suggested models are potentially useful in predicting tau pathology, and might be utilized practically in the field.
The role of C1 inhibitor and complement as acute phase reactants: are we missing the diagnosis of hereditary angioedema?
Authors: Stepaniuk Peter , Bosonea Ana-Maria , Pourshahnazari Persia , Roos Adrienne , Kanani Amin
Published: October 2021

Background

C1 inhibitor (C1-INH) and complement 4 (C4) have historically been referred to as positive acute phase reactants, however this has never been evaluated in hereditary angioedema (HAE) patients. Low function of C1-INH and low levels of C4 are important in the diagnosis of HAE type 1 and 2. If C1-INH and/or C4 are significant acute phase reactants, their levels may be falsely “normal” in patients with HAE when measured during times of infection or inflammation resulting in missed or delayed diagnosis.

Case presentation

We present a case series of four HAE patients who had C4, C1-INH, c-reactive protein (CRP) and ferritin measured at baseline and again during a self-reported upper respiratory tract infection (URTI) or flu-like illness. We did not identify any HAE patients who had a significant change in their C1-INH functional level in the context of a mild infection. However, the C4 level did increase into the normal range on three occasions (2 patients, with 1 patient having elevation during two separate illnesses).

Conclusions

C1 inhibitor may not be a clinically significant acute phase protein and appears to still be a reliable diagnostic marker of hereditary angioedema, even in times of modest acute inflammation, unlike complement C4 which can be elevated in this setting.
Massive aspiration syndrome: a possible indication for “emergent” veno-venous extracorporeal membrane oxygenation?: a case report
Authors: Gamberini Emiliano , Poletti Venerino , Russo Emanuele , Circelli Alessandro , Benni Marco , Scognamiglio Giovanni , Santonastaso Domenico Pietro , Martino Costanza , Domenichini Linda , Biondi Romina , Bastoni Giorgia , Brogi Etrusca , Ansaloni Luca , Coccolini Federico , Fugazzola Paola , Spiga Martina , Agnoletti Vanni
Published: October 2021

Background

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is usually performed in cases of severe respiratory failure in which conventional and advanced mechanical ventilation strategies are ineffective in achieving true lung-protective ventilation, thus triggering ventilatory-induced lung injury. If circulatory failure coexists, veno-arterial ECMO (VA-ECMO) may be preferred over VV-ECMO because of its potential for circulatory support. In VA-ECMO, the respiratory contribution is less effective and the complication rate is higher than in the VV configuration.

Case presentation

The authors present a case in which VV-ECMO was performed in an emergency setting to treat a 68-year-old White male patient who experienced acute respiratory failure after massive aspiration. Despite intubation and intensive care unit admission, multiple organ failure occurred suddenly, thus prompting referral to a level-1 trauma center with an ECMO facility. The patient’s condition slowly improved with VV-ECMO support along with standard treatment for hemodynamic impairment. VV-ECMO was discontinued on day 8. The patient was extubated on day 14 and discharged home fully recovered 34 days after the event.

Conclusions

Attention was focused on the decision to initiate VV-ECMO support even in the presence of severe hemodynamic derangement, although VA-ECMO could have provided better hemodynamic support but less effective respiratory support.
Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia with e1a3 BCR-ABL1 transcript in a Nigerian with sickle cell anemia: a case report
Authors: Ahmed Ibrahim O. , Ochogwu Lauretta O. , Owojuyigbe Temilola O. , Akinola Norah O. , Durosinmi Muheez A.
Published: October 2021

Background

The occurrence of acute leukemia in patients with sickle cell anemia is uncommon. The Philadelphia chromosome is the hallmark of chronic myeloid leukemia. However, it may also be associated with acute lymphoblastic leukemia and acute myeloblastic leukemia. The commonBCR-ABL1transcripts seen in acute lymphoblastic leukemia are e1a2, e13a2, and e14a2, while other transcripts such as e1a3, e13a3, and e6a2 occur rarely. This report describes the presentation, management, and outcome of the occurrence of B-cell acute lymphoblastic leukemia with the rare e1a3BCR-ABL1transcript in a patient with sickle cell anemia.

Case presentation

A 19-year-old male Nigerian, a known sickle cell anemia patient was admitted on account of severe vaso-occlusive crisis. Examination revealed fever, palor, and jaundice. Full blood count showed anemia and leukocytosis. Peripheral blood and bone marrow smears revealed numerous large and small lymphoblasts in keeping with the L2 subtype of acute lymphoblastic leukemia based on the French–American–British classification. Further evaluation was in keeping with a diagnosis ofBCR-ABL1-positive mature B-cell acute lymphoblastic leukemia associated with the rare e1a3 transcript. He was commenced simultaneously on induction chemotherapy and Imatinib while being prepared for allogeneic stem cell transplantation. However, he died  six  months after diagnosis from meningoencephalitis.

Conclusion

The occurrence of acute lymphoblastic leukemia with a rareBCR-ABL1e1a3 transcript in association with sickle cell anemia is uncommon and associated with poor prognosis.
Bipolar disorder with Melnick–Needles syndrome and periventricular nodular heterotopia: two case reports and a review of the literature
Authors: Riccio Maria Pia , D’Andrea Giuseppe , Sarnataro Emilia , Marino Maria , Bravaccio Carmela , Albert Umberto
Published: October 2021

Background

Melnick–Needles syndrome and periventricular nodular heterotopia are two usually mutually exclusive phenotypes of F-actin-binding cytoskeletal phosphoprotein Filamin-A mutations. Melnick–Needles syndrome is a rare X-linked condition that is lethal in males and shows great phenotypic variability in affected females. It is caused by mutations inFilamin-Agene, which encodes the protein Filamin A. Defects of the humanFilamin-Agene also cause X-linked periventricular nodular heterotopia, a malformation of neuronal migration characterized by nodules of neurons in inappropriate location adjacent to the walls of the lateral ventricles.

Case presentation

We report on two Caucasian adolescent females, sisters, diagnosed with Melnick–Needles syndrome and bilateral periventricular nodular heterotopia, who developed bipolar disorder and somatic symptoms disorder at a young age. We also present a review of the literature about mental disorders associated with periventricular nodular heterotopia. Our report shows that patients presenting with atypical and heterogeneous psychiatric disease may have an underrecognized anatomical brain abnormality on genetic basis.

Conclusions

We found records of psychiatric disorders associated with periventricular nodular heterotopia; nevertheless, this is the first report of bipolar disorder occurring in individuals with periventricular nodular heterotopia, and the first report of any psychiatric disorder in individuals affected by Melnick–Needles syndrome. In conclusion, this case report may contribute to characterizing the phenotype of this very rare syndrome.
Human adipose-derived stromal cells transplantation prolongs reproductive lifespan on mouse models of mild and severe premature ovarian insufficiency
Authors: Salvatore Giulia , De Felici Massimo , Dolci Susanna , Tudisco Cosimo , Cicconi Rosella , Campagnolo Luisa , Camaioni Antonella , Klinger Francesca Gioia
Published: October 2021

Background

Although recent studies have investigated the ability of Mesenchymal Stromal Cells (MSCs) to alleviate short-term ovarian damage in animal models of chemotherapy-induced Premature Ovarian Insufficiency (POI), no data are available on reproductive lifespan recovery, especially in a severe POI condition. For this reason, we investigated the potential of MSCs isolated from human adipose tissue (hASCs), since they are easy to harvest and abundant, in ameliorating the length and performance of reproductive life in both mild and severe chemotherapy-induced murine POI models.

Methods

Mild and severe POI models were established by intraperitoneally administering a light (12 mg/kg busulfan + 120 mg/kg cyclophosphamide) or heavy (30 mg/kg busulfan + 120 mg/kg cyclophosphamide) dose of chemotherapy, respectively, in CD1 mice. In both cases, a week later, 1 × 106 hASCs were transplanted systemically through the tail vein. After four additional weeks, some females were sacrificed to collect ovaries for morphological evaluation. H&E staining was performed to assess stroma alteration and to count follicle numbers; immunofluorescence staining for αSMA was used to analyse vascularization. Of the remaining females, some were mated after superovulation to collect 2-cell embryos in order to evaluate their pre-implantation developmental capacity in vitro, while others were naturally mated to monitor litters and reproductive lifespan length. F1 litters’ weight, ovaries and reproductive lifespan were also analysed.

Results

hASC transplantation alleviated ovarian weight loss and size decrease and reduced alterations on ovarian stroma and vasculature, concurrently preventing the progressive follicle stockpile depletion caused by chemotherapy. These effects were associated with the preservation of the oocyte competence to develop into blastocyst in vitro and, more interestingly, with a significant decrease of chemotherapy-induced POI features, like shortness of reproductive lifespan, reduced number of litters and longer time to plug (the latter only presented in the severe POI model).

Conclusion

Human ASC transplantation was able to significantly reduce all the alterations induced by the chemotherapeutic treatment, while improving oocyte quality and prolonging reproductive functions, thus counteracting infertility. These results, strengthened by the use of an outbred model, support the potential applications of hASCs in women with POI, nowadays mainly induced by anticancer therapies.

Graphic abstract
A novel minimally invasive OFM technique with orthotopic transplantation of hUC-MSCs and in vivo monitoring of liver metabolic microenvironment in liver fibrosis treatment
Authors: Yang Hui , Xie Yuanyuan , Li Tuo , Liu Shuo , Zeng Sheng , Wang Bin
Published: October 2021

Background

Mesenchymal stromal cells (MSCs) transplantation showed promising therapeutic results in liver fibrosis. However, efficient cell delivery method is urgently needed and the therapeutic mechanism remains unclear. This study focused on developing a minimally invasive open-flow microperfusion (OFM) technique, which combined orthotopic transplantation of human umbilical cord-derived (hUC)-MSCs to liver and in vivo monitoring of liver microenvironment in mice with CCl4-induced liver fibrosis.

Methods

The therapeutic potential of OFM route was evaluated by comparing OFM with intravenous (IV) injection route in terms of hUC-MSCs engraftment at the fibrosis liver, liver histopathological features, liver function and fibrotic markers expression after hUC-MSCs administration. OFM was also applied to sample liver interstitial fluid in vivo, and subsequent metabolomic analysis was performed to investigate metabolic changes in liver microenvironment.

Results

Compared with IV route, OFM route caused more hUC-MSCs accumulation in the liver and was more effective in improving the remodeling of liver structure and reducing collagen deposition in fibrotic liver. OFM transplantation of hUC-MSCs reduced blood ALT, AST, ALP and TBIL levels and increased ALB levels, to a greater extent than IV route. And OFM route appeared to have a more pronounced effect on ameliorating the CCl4-induced up-regulation of the fibrotic markers, such as α-SMA, collagen I and TGF-β. In vivo monitoring of liver microenvironment demonstrated the metabolic perturbations induced by pathological condition and treatment intervention. Two metabolites and eight metabolic pathways, which were most likely to be associated with the liver fibrosis progression, were regulated by hUC-MSCs administration.

Conclusion

The results demonstrated that the novel OFM technique would be useful for hUC-MSCs transplantation in liver fibrosis treatment and for monitoring of the liver metabolic microenvironment to explore the underlying therapeutic mechanisms.
sTNFRII-Fc modification protects human UC-MSCs against apoptosis/autophagy induced by TNF-α and enhances their efficacy in alleviating inflammatory arthritis
Authors: Zhao Yingjie , Yang Xuezhi , Li Siyu , Zhang Bingjie , Li Susu , Wang Xinwei , Wang Yueye , Jia Chengyan , Chang Yan , Wei Wei
Published: October 2021

Background

Tumor necrosis factor (TNF)-α inhibitors represented by Etanercept (a fusion protein containing soluble TNF receptor II (sTNFRII) and the Fc segment of human IgG1) play a pivotal role in Rheumatoid arthritis (RA) treatment. However, long-term use increases the risk of infection and tumors for their systemic inhibition of TNF-α, which disrupts the regular physiological function of this molecular. Mesenchymal stem cells (MSCs)-based delivery system provides new options for RA treatment with their “homing” and immune-regulation capacities, whereas inflammatory environment (especially TNF-α) is not conducive to MSCs' therapeutic effects by inducing apoptosis/autophagy. Here, we constructed a strain of sTNFRII-Fc-expressing MSCs (sTNFRII-MSC), aiming to offset the deficiency of those two interventions.

Methods

Constructed sTNFRII-Fc lentiviral vector was used to infect human umbilical cord-derived MSCs, and sTNFRII-MSC stable cell line was generated by monoclonal cultivation. In vitro and vivo characteristics of sTNFRII-MSC were assessed by coculture assay and an acute inflammatory model in NOD/SCID mice. The sTNFRII-MSC were transplanted into CIA model, pathological and immunological indicators were detected to evaluate the therapeutic effects of sTNFRII-MSC. The distribution of sTNFRII-MSC was determined by immunofluorescence assay. Apoptosis and autophagy were analyzed by flow cytometry, western blot and immunofluorescence.

Results

sTNFRII-Fc secreted by sTNFRII-MSC present biological activity both in vitro and vivo. sTNFRII-MSC transplantation effectively alleviates mice collagen-induced arthritis (CIA) via migrating to affected area, protecting articular cartilage destruction, modulating immune balance and sTNFRII-MSC showed prolonged internal retention via resisting apoptosis/autophagy induced by TNF-α.

Conclusion

sTNFRII-Fc modification protects MSCs against apoptosis/autophagy induced by TNF-α, in addition to releasing sTNFRII-Fc neutralizing TNF-α to block relevant immune-inflammation cascade, and thus exert better therapeutic effects in alleviating inflammatory arthritis.
Endometrial mesenchymal stem/stromal cells: The Enigma to code messages for generation of functionally active regulatory T cells
Authors: Aleahmad Mehdi , Bozorgmehr Mahmood , Nikoo Shohreh , Ghanavatinejad Alireza , Shokri Mohammad-Reza , Montazeri Samaneh , Shokri Fazel , Zarnani Amir-Hassan
Published: October 2021

Background

Regulatory T cells (Tregs) play an important role in fine-tuning of immune responses and are pivotal for a successful pregnancy. Recently, the importance of mesenchymal stem cells in regulation of immune responses in general and Tregs in particular has been highlighted. Here, we hypothesized that menstrual stromal/stem cells (MenSCs) contribute to uterine immune system regulation through induction of functionally active Tregs.

Methods

MenSCs were collected from 18 apparently healthy women and characterized. Bone marrow mesenchymal stem cells (BMSCs) served as a control. The effect of MenSCs on proliferation of anti-CD3/CD28-stimulated T CD4 + cells and generation of Tregs with or without pre-treatment with mitomycin C, IFN-γ and IL-1β was evaluated by flow cytometry. The potential role of IDO, PGE2, IL-6, IL-10, and TGF-β on proliferation of T CD4 + cells and generation of Tregs was assessed using blocking antibodies or agents. IDO activity was evaluated in MenSCs and BMSCs culture supernatants by a colorimetric assay. IL-10 and IFN-γ production in MenSCs-primed T CD4 + was measured using intracellular staining. To investigate the functional properties of Tregs induced by MenSCs, Treg cells were isolated and their functional property to inhibit proliferation of anti-CD3/CD28-stimulated PBMCs was assessed by flow cytometry.

Results

According to the results, proliferation of T CD4 + lymphocytes was enhanced in the presence of MenSCs, while pre-treatment of MenSCs with pro-inflammatory cytokines reversed this effect. PGE2 and IDO were the major players in MenSCs-induced T cell proliferation. Non-treated MenSCs decreased the frequency of Tregs, whereas after pre-treatment with IFN-γ and IL-1β, they induced functional Tregs with ability to inhibit the proliferation of anti-CD3/CD28-stimulated PBMCs. This effect was mediated through IL-6, IL-10, TGF-β and IDO. IFN-γ/IL-1β-treated MenSCs induced IL-10 and IFN-γ production in CD4 + T cells.

Conclusion

Collectively, these findings indicate that immunomodulatory impact of menstrual blood stem cells (MenSCs) on generation of Tregs and inhibition of T cells proliferation is largely dependent on pre-treatment with IFN-γ and IL-1β. This is the first report on immunomodulatory impact of MenSCs on Tregs and highlights the pivotal role of endometrial stem cells in regulation of local endometrial immune responses.
Sex and gender specific health topics in medical student learners: pulse check eight years later
Authors: Rydberg Ann , Buras Matthew R. , Quillen Jaxon , Miller Virginia , Kling Juliana M.
Published: October 2021

Background

An essential component of patient-centered, individualized medicine is considering how sex and gender affect mechanisms of health and disease.

Objectives

To assess medical students’ current knowledge of sex and gender specific health (SGSH) concepts compared to results from the same survey in 2012 to better inform development of curricular materials for medical education.

Methods

A previously designed survey tool, which assessed current knowledge of sex and gender-based medicine of medical students, was emailed to all Mayo Clinic Alix School of Medicine (MCASOM) students on Minnesota, Arizona, and Florida campuses in 2020. Descriptive and qualitative thematic results were compared to the same survey administered in 2012 to students enrolled in MCASOM. Changes in the inclusion of SGSH topics were assessed over the eight years.

Results

One hundred and one of 365 (27.7% response rate) surveys were returned with 2:1 female to male respondents with representation from all 4 years. The definitions of the terms “sex” and “gender” were correctly identified by most respondents (93.1%). However, only 36% (12/33) of questions related to other medical knowledge on SGSH topics had more than a 50% correct response rate. More than half of the students reported that SGSH topics were included in Gynecology, Cardiology, Pediatrics, and Immunology. SGSH topics were reported as not being routinely covered in Neurology and Nephrology, although more students said they were in 2020 then 2012. Sixty-two percent of students favored increasing SGSH in the current curriculum.

Conclusions

Medical students appear to understand the definition of and importance of SGSH in education. While some improvements in coverage by subject matter and topic area appear to have occurred as reported by medical students, opportunity remains to more fully integrate SGSH concepts in medical school curricula.
Sex differences in recovery of motor function in a rhesus monkey model of cortical injury
Authors: Bottenfield Karen R. , Bowley Bethany G. E. , Pessina Monica A. , Medalla Maria , Rosene Douglas L. , Moore Tara L.
Published: October 2021

Background

Stroke disproportionately affects men and women, with women over 65 years experiencing increased severity of impairment and higher mortality rates than men. Human studies have explored risk factors that contribute to these differences, but additional research is needed to investigate how sex differences affect functional recovery and hence the severity of impairment. In the present study, we used our rhesus monkey model of cortical injury and fine motor impairment to compare sex differences in the rate and degree of motor recovery following this injury.

Methods

Aged male and female rhesus monkeys were trained on a task of fine motor function of the hand before undergoing surgery to produce a cortical lesion limited to the hand area representation of the primary motor cortex. Post-operative testing began two weeks after the surgery and continued for 12 weeks. All trials were video recorded and latency to retrieve a reward was quantitatively measured to assess the trajectory of post-operative response latency and grasp pattern compared to pre-operative levels.

Results

Postmortem analysis showed no differences in lesion volume between male and female monkeys. However, female monkeys returned to their pre-operative latency and grasp patterns significantly faster than males.

Conclusions

These findings demonstrate the need for additional studies to further investigate the role of estrogens and other sex hormones that may differentially affect recovery outcomes in the primate brain.
An ontology network for Diabetes Mellitus in Mexico
Authors: Reyes-Peña Cecilia , Tovar Mireya , Bravo Maricela , Motz Regina
Published: October 2021

Background

Medical experts in the domain of Diabetes Mellitus (DM) acquire specific knowledge from diabetic patients through monitoring and interaction. This allows them to know the disease and information about other conditions or comorbidities, treatments, and typical consequences of the Mexican population. This indicates that an expert in a domain knows technical information about the domain and contextual factors that interact with it in the real world, contributing to new knowledge generation. For capturing and managing information about the DM, it is necessary to design and implement techniques and methods that allow: determining the most relevant conceptual dimensions and their correct organization, the integration of existing medical and clinical information from different resources, and the generation of structures that represent the deduction process of the doctor. An Ontology Network is a collection of ontologies of diverse knowledge domains which can be interconnected by meta-relations. This article describes an Ontology Network for representing DM in Mexico, designed by a proposed methodology. The information used for Ontology Network building include the ontological resource reuse and non-ontological resource transformation for ontology design and ontology extending by natural language processing techniques. These are medical information extracted from vocabularies, taxonomies, medical dictionaries, ontologies, among others. Additionally, a set of semantic rules has been defined within the Ontology Network to derive new knowledge.

Results

An Ontology Network for DM in Mexico has been built from six well-defined domains, resulting in new classes, using ontological and non-ontological resources to offer a semantic structure for assisting in the medical diagnosis process. The network comprises 1367 classes, 20 object properties, 63 data properties, and 4268 individuals from seven different ontologies. Ontology Network evaluation was carried out by verifying the purpose for its design and some quality criteria.

Conclusions

The composition of the Ontology Network offers a set of well-defined ontological modules facilitating the reuse of one or more of them. The inclusion of international vocabularies as SNOMED CT or ICD-10 reinforces the representation by international standards. It increases the semantic interoperability of the network, providing the opportunity to integrate other ontologies with the same vocabularies. The ontology network design methodology offers a guide for ontology developers about how to use ontological and non-ontological resources in order to exploit the maximum of information and knowledge from a set of domains that share or not information.
Evaluation of intracellular processes in quinolinic acid-induced brain damage by imaging reactive oxygen species generation and mitochondrial complex I activity
Authors: Hosoi Rie , Fujii Yuka , Hiroyuki Ohba , Shukuri Miho , Nishiyama Shingo , Kanazawa Masakatsu , Todoroki Kenichiro , Arano Yasushi , Sakai Toshihiro , Tsukada Hideo , Inoue Osamu
Published: October 2021

Purpose

Our study aimed to elucidate the intracellular processes associated with quinolinic acid (QA)-induced brain injury by acquiring semiquantitative fluorescent images of reactive oxygen species (ROS) generation and positron emission tomography (PET) images of mitochondrial complex I (MC-I) activity.

Methods

Ex vivo fluorescent imaging with dihydroethidium (DHE) and PET scans with 18F-BCPP-EF were conducted at 3 h and 24 h after QA injection into the rat striatum. Immunohistochemical studies were performed 24 h after QA injection into the rat brain using monoclonal antibodies against neuronal nuclei (NeuN) and CD11b.

Results

A strong DHE-derived fluorescent signal was detected in a focal area within the QA-injected striatum 3 h after QA injection, and increased fluorescent signal spread throughout the striatum and parts of the cerebral cortex after 24 h. By contrast, 18F-BCPP-EF uptake in the QA-injected rat brain was unchanged after 3 h and markedly decreased after 24 h, not only in the striatum but also in the cerebral hemisphere. The fluorescent signal in the striatum 24 h after QA injection colocalised with microglial marker expression.

Conclusions

We successfully obtained functional images of focal ROS generation during the early period of excitotoxic injury, and microglial ROS generation and mitochondrial dysfunction were observed during the progression of the inflammatory response. Both ex vivo DHE imaging and in vivo 18F-BCPP-EF-PET were sufficiently sensitive to detect the respective processes of QA-induced brain damage. Our study contributes to the functional imaging of multiple events during the pathological process.
COVID-19 healthcare cost and length of hospital stay in Turkey: retrospective analysis from the first peak of the pandemic
Authors: Oksuz Ergun , Malhan Simten , Gonen Mustafa Sait , Kutlubay Zekayi , Keskindemirci Yilmaz , Tabak Fehmi
Published: October 2021

Background

During the COVID-19 pandemic, health care systems are under extreme pressure. This study analyzed health care resource use (HCRU) and costs in patients admitted to the hospital for COVID-19 and aimed to estimate the one-year direct medical cost of the disease in Turkey.

Methods

This retrospective cohort study was conducted between March and July 2020 in a tertiary hospital (n = 1056) in Istanbul. Patient demographics, clinical and treatment characteristics at admission, comorbidities, disease severity, and costs from a payer perspective were evaluated using the microcosting method. The results include LOS, hospital costs, and univariate and generalized linear models to investigate influencing factors. The data were extrapolated to provide a country-level estimate.

Results

The mean length of stay was 9.1 days (SD 6.9). The mean length of stay was 8.0 days (4.7) for patients hospitalized in wards versus 14.8 days (SD 12.0) for patients hospitalized in the ICU. In univariate analysis, several factors, including O2therapy (+ 3.7 days), high CRP > 41.8 mg/L (+ 3.8 days), and elevated ferritin (+ 3.5), were found to be associated with a longer LOS (p < 0.05).

The direct annual medical cost of COVID-19 was estimated at PPP$ 2.1 billion. The COVID-19 pandemic resulted in a direct medical burden that corresponds to 2.0% of the government health expenditures and 0.8 per thousand of Turkey’s gross domestic product (GDP).

Conclusions

Estimating the impact of this pandemic in terms of HCRU and costs to the health care system can help design strategies to manage the pandemic.
RhoA enhances osteosarcoma resistance to MPPa-PDT via the Hippo/YAP signaling pathway
Authors: Zhan Fangbiao , He Tao , Chen Zhiyu , Zuo Qiang , Wang Yang , Li Qiaochu , Zhong Shenxi , Ou Yunsheng
Published: October 2021

Background

Osteosarcoma (OS) is the most prevalent primary bone malignancy affecting adolescents, yet the emergence of chemoradiotherapeutic resistance has limited efforts to cure affected patients to date. Pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) is a recently developed, minimally invasive treatment for OS that is similarly constrained by such therapeutic resistance. This study sought to explore the mechanistic basis for RhoA-activated YAP1 (YAP)-mediated resistance in OS.

Methods

The relationship between YAP expression levels and patient prognosis was analyzed, and YAP levels in OS cell lines were quantified. Immunofluorescent staining was used to assess YAP nuclear translocation. OS cell lines (HOS and MG63) in which RhoA and YAP were knocked down or overexpressed were generated using lentiviral vectors. CCK-8 assays were used to examine OS cell viability, while the apoptotic death of these cells was monitored via Hoechst staining, Western blotting, and flow cytometry. Tumor-bearing nude mice were additionally used to assess the relationship between lentivirus-mediated alterations in RhoA expression and MPPa-PDT treatment outcomes. TUNEL and immunohistochemical staining approaches were leveraged to assess apoptotic cell death in tissue samples.

Results

OS patients exhibited higher levels of YAP expression, and these were correlated with a poor prognosis. MPPa-PDT induced apoptosis in OS cells, and such MPPa-PDT-induced apoptosis was enhanced following YAP knockdown whereas it was suppressed by YAP overexpression. RhoA and YAP expression levels were positively correlated in OS patients, and both active and total RhoA protein levels rose in OS cells following MPPa-PDT treatment. When RhoA was knocked down, levels of unphosphorylated YAP and downstream target genes were significantly reduced, while RhoA/ROCK2/LIMK2 pathway phosphorylation was suppressed, whereas RhoA overexpression resulted in the opposite phenotype. MPPa-PDT treatment was linked to an increase in HMGCR protein levels, and the inhibition of RhoA or HMGCR was sufficient to suppress RhoA activity and to decrease the protein levels of YAP and its downstream targets. Mevalonate administration partially reversed these reductions in the expression of YAP and YAP target genes. RhoA knockdown significantly enhanced the apoptotic death of OS cells in vitro and in vivo following MPPa-PDT treatment, whereas RhoA overexpression had the opposite effect.

Conclusions

These results suggest that the mevalonate pathway activates RhoA, which in turn activates YAP and promotes OS cell resistance to MPPa-PDT therapy. Targeting the RhoA/ROCK2/LIMK2/YAP pathway can significantly improve the efficacy of MPPa-PDT treatment for OS.
Joint spectral efficiency optimization of uplink and downlink for massive MIMO-enabled wireless energy harvesting systems
Authors: Sun Wenfeng , Liu Chen , Qian Mujun , Chen Yan , Xu Shu
Published: October 2021

This paper investigated the spectral efficiency (SE) in massive multiple-input multiple-output systems, where all terminals have no fixed power supply and thus need to replenish energy via the received signals from the base station. The hybrid wireless energy harvesting (EH) protocol is applied for each terminal, which can switch to either existing time-switching (TS) protocol or power-splitting (PS) protocol. Based on the hybrid wireless EH protocol, a general system model is developed, which can switch to either only uplink data transmission or only downlink data transmission. As a result, a general analytical framework is formulated. Then, closed-form lower bound expressions on SE for each terminal are obtained on the uplink and downlink, respectively. According to these expressions, the joint SE of uplink and downlink maximization problem is designed with some practical constraints. As the designed optimization problem is non-linear and non-convex, it is hard to solve directly. To provide a solution, an iteration algorithm is proposed by utilizing one-dimensional search technique and successive approximation method based on geometric program. Additionally, the convergence and complexity of the proposed algorithm are discussed as well. Finally, the feasibility of the proposed algorithm is analyzed by simulations. Numerical results manifest that the proposed algorithm can provide good SE by optimizing relevant system parameters, and the system model can help to discuss the TS, PS or hybrid protocol for only uplink data transmission, only downlink data transmission or joint data transmission of uplink and downlink in the considered system.
On Lipschitz continuity with respect to the Poincaré metric of linear contractions between Möbius gyrovector spaces
Authors: Watanabe Keiichi
Published: October 2021

For every linear operator between inner product spaces whose operator norm is less than or equal to one, we show that the restriction to the Möbius gyrovector space is Lipschitz continuous with respect to the Poincaré metric. Moreover, the Lipschitz constant is precisely the operator norm.
A fractional q-integral operator associated with a certain class of q-Bessel functions and q-generating series
Authors: Al-Omari Shrideh , Suthar Dayalal , Araci Serkan
Published: October 2021

This paper deals with Al-Salam fractional q-integral operator and its application to certain q-analogues of Bessel functions and power series. Al-Salam fractional q-integral operator has been applied to various types of q-Bessel functions and some power series of special type. It has been obtained for basic q-generating series, q-exponential and q-trigonometric functions as well. Various results and corollaries are provided as an application to this theory.
Blow-up of solutions for a quasilinear system with degenerate damping terms
Authors: Boulaaras Salah , Choucha Abdelbaki , Agarwal Praveen , Abdalla Mohamed , Idris Sahar Ahmed
Published: October 2021

In this work, we consider a quasilinear system of viscoelastic equations with degenerate damping and general source terms. According to some suitable hypothesis, we study the blow-up of solutions. This is the general case of the recent results of Boulaaras’ works (Bull. Malays. Math. Sci. Soc. 43:725–755, 2020) and (Appl. Anal. 99:1724–1748, 2020).