bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the correlation between activating transcription factor 3 expression in the human coronary artery and atherosclerotic plaque stability
Authors: Peng J. , Le C. Y. , Xia B. , Wang J. W. , Liu J. J. , Li Z. , Zhang Q. J. , Zhang Q. , Wang J. , Wan C. W.
Published: July 2021

Background

Activating transcription factor 3 (ATF3) is an early response gene that is activated in response to atherosclerotic stimulation and may be an important factor in inhibiting the progression of atherosclerosis. In this study, we directly measured the expression of ATF3 and inflammatory factors in human coronary atherosclerotic plaques to examine the relationship between ATF3 expression, inflammation and structural stability in human coronary atherosclerotic plaques.

Methods

A total of 68 coronary artery specimens were collected from the autopsy group, including 36 cases of sudden death from coronary heart disease (SCD group) and 32 cases of acute death caused by mechanical injury with coronary atherosclerosis (CHD group). Twenty-two patients who had no coronary heart disease were collected as the control group (Con group). The histological structure of the coronary artery was observed under a light microscope after routine HE staining, and the intimal and lesion thicknesses, thickness of the fibrous cap, thickness of necrosis core, degree of lumen stenosis were assessed by image analysis software. Western blotting and immunohistochemistry were used to measure the expression and distribution of ATF3, inflammatory factors (CD45, IL-1β, TNF-α) and matrix metalloproteinase-9 (MMP-9) and vascular cell adhesion molecule 1 (VCAM1) in the coronary artery. The Pearson correlation coefficient was used to analyse the correlation between ATF3 protein expression and inflammatory factors and between ATF3 protein expression and structure-related indexes in the lesion group.

Results

Compared with those in the control group, the intima and necrotic core in the coronary artery were thickened, the fibrous cap became thin and the degree of vascular stenosis was increased in the lesion group, while the intima and necrotic core became thicker and the fibrous cap became thinner in the SCD group than in the CHD group (P < 0.05). There was no or low expression of ATF3, inflammatory factors, VCAM1 and MMP-9 in the control group, and the expression of inflammatory factors, VCAM1 and MMP-9 in the SCD group was higher than that in CHD group, while the expression of ATF3 in the SCD group was significantly lower than that in CHD group (P < 0.05). In the lesion group, the expression of ATF3 was negatively correlated with intimal and necrotic focus thickness, positively correlated with fibrous cap thickness (P < 0.01), and negatively correlated with inflammatory factors, VCAM1 and MMP-9 (P < 0.01).

Conclusions

The expression of ATF3 may be related to the progression and stability of atherosclerotic plaques, and may affect the structural stability of atherosclerotic plaques by regulating the inflammatory response, thus participating in the regulation of atherosclerotic progression.
Overcoming the problems caused by collinearity in mixed-effects logistic model: determining the contribution of various types of violence on depression in pregnant women
Authors: Khalili Sanaz , Faradmal Javad , Mahjub Hossein , Moeini Babak , Ezzati-Rastegar Khadijeh
Published: July 2021

Background

Collinearity is a common and problematic phenomenon in studies on public health. It leads to inflation in variance of estimator and reduces test power. This phenomenon can occur in any model. In this study, a new ridge mixed-effects logistic model (RMELM) is proposed to overcome consequences of collinearity in correlated binary responses.

Methods

Parameters were estimated through penalized log-likelihood with combining expectation maximization (EM) algorithm, gradient ascent, and Fisher-scoring methods. A simulation study was performed to compare new model with mixed-effects logistic model(MELM). Mean square error, relative bias, empirical power, and variance of random effects were used to evaluate RMELM. Also, contribution of various types of violence, and intervention on depression among pregnant women experiencing intimate partner violence(IPV) were analyzed by new and previous models.

Results

Simulation study showed that mean square errors of fixed effects were decreased for RMELM than MELM and empirical power were increased. Inflation in variance of estimators due to collinearity was clearly shown in the MELM in data on IPV and RMELM adjusted the variances.

Conclusions

According to simulation results and analyzing IPV data, this new estimator is appropriate to deal with collinearity problems in the modelling of correlated binary responses.
A generic outcome assessment of mobility capacity in neurorehabilitation: measurement properties of the de Morton Mobility Index
Authors: Braun Tobias , Marks Detlef , Thiel Christian , Grüneberg Christian
Published: July 2021

Background

Mobility capacity is a key outcome domain in neurorehabilitation. The de Morton Mobility Index (DEMMI), an established and generic outcome assessment of mobility capacity in older patients, is promising for use in neurorehabilitation. The aim of this study was to examine the measurement properties of the DEMMI in rehabilitation inpatients with neurological conditions.

Methods

Cross-sectional study including a mixed sample of adult inpatients in a neurorehabilitation hospital. Structural validity, unidimensionality and measurement invariance (Rasch analysis), construct validity, internal consistency reliability, and inter-rater reliability of the DEMMI (scale range: 0–100 points) were established. The minimal detectable change, the 95% limits of agreement, and possible floor and ceiling effects were calculated to indicate interpretability.

Results

We analyzed validity (n = 348) and reliability (n = 133) in two samples. In both samples, the majority of participants had a sub-acute stroke or Parkinson’s disease.

Rasch analysis indicated unidimensionality with an overall fit to the model (chi-square = 59.4, P = 0.074). There was no relevant measurement invariance by disease group. Hypotheses-based correlation analyses (DEMMI and other functional outcome assessments) showed sufficient construct validity. Internal consistency reliability (Cronbach’s alpha = 0.94) and inter-rater reliability (intraclass correlation coefficient = 0.94; 95% confidence interval: 0.91–0.95) were sufficient. The minimal detectable change with 90% confidence was 15.0 points and the limits of agreement were 39%. No floor or ceiling effects were observed.

Conclusions

Results indicate sufficient measurement properties of the DEMMI in rehabilitation inpatients with neurological conditions. The DEMMI can be used as a generic outcome assessment of mobility capacity in neurorehabilitation.

Trial registration

German Clinical Trials Register (DRKS00004681). Registered May 6, 2013.
The effects of bright light treatment on affective symptoms in people with dementia: a 24-week cluster randomized controlled trial
Authors: Kolberg Eirin , Hjetland Gunnhild Johnsen , Thun Eirunn , Pallesen Ståle , Nordhus Inger Hilde , Husebo Bettina S. , Flo-Groeneboom Elisabeth
Published: July 2021

Background

The majority of people with dementia have behavioral and psychological symptoms of dementia (BPSD), including depression, anxiety and agitation. These may be elicited or aggravated by disrupted circadian rhythms. Bright light treatment (BLT) is a promising non-pharmacological approach to the management of BPSD, but previous research has yielded mixed results.

Methods

Eight nursing home dementia units (1 unit = 1 cluster) with 78 patients were invited to participate in a cluster randomized controlled trial from September 2017 to April 2018 investigating the effects of BLT on sleep and circadian rhythms (primary outcome) and BPSD (secondary outcome). Ceiling mounted LED-panels were installed in the intervention group (four units), providing light at 1000 lx and 6000 K (vertically at 1.2 m) between 10 a.m. and 3 p.m., with lower values in the mornings and evenings. Standard indoor light was used in the control group (four units). BPSD were assessed with The Cornell Scale for Depression in Dementia (CSDD) and the Neuropsychiatric Inventory Nursing Home Version (NPI-NH). Data collection took place at baseline and after 8, 16 and 24 weeks. Multilevel regression models with and without false discovery rate correction were used for the analysis, with baseline values and dementia stage entered as covariates.

Results

Sixty-nine patients were included in the study at baseline. Compared to the control group, the intervention group had a larger reduction on the composite scores of both the CSDD (95% CI = − 6.0 – − 0.3) and the NPI-NH (95% CI = − 2.2 – − 0.1), as well as on the NPI-NH Affect sub-syndrome, and the CSDD Mood related signs sub-scale at follow-up after 16 weeks. With FDR correction, the group difference was significant on the CSDD Mood related signs sub-scale (95% CI = − 2.7 – − 0.8) and the NPI-NH Affect sub-syndrome (95% CI = − 1.6 – − 0.2). No differences were found between conditions at weeks 8 or 24.

Conclusion

Compared to the control condition, affective symptoms were reduced after 16 weeks in the group receiving BLT, suggesting BLT may be beneficial for nursing home patients with dementia.

Trial registration

ClinicalTrials.govIdentifier:NCT03357328. Retrospectively registered on November 29, 2017.
Factor structure and sex invariance of the temporal experience of pleasure scale (TEPS) in Chinese university students and clinical population
Authors: Fang Shulin , Huang Xiaodan , Zhang Panwen , He Jiayue , Luo Xingwei , Zhang Jianghua , Xiong Yan , Luo Fusheng , Wang Xiaosheng , Yao Shuqiao , Wang Xiang
Published: July 2021

Background

A motivation dimension of the core psychiatric symptom anhedonia additional has been suggested. The Temporal Experience of Pleasure Scale (TEPS) has been reported to assess anticipatory and consummatory pleasure separately in multiple factor-structure models. This study explored the factor structure of a Chinese version of the 18-item TEPS and further explored the measurement invariance of the TEPS across sex and clinical status (non-clinical, psychiatric).

Methods

Best-fit factor structure of the TEPS was examined in a non-clinical cohort of 7410 undergraduates, randomized into sample 1 (N = 3755) for exploratory factor analysis (EFA) and sample 2 (N = 3663) for confirmatory factor analysis (CFA). Additionally, serial CFA was conducted to evaluate measurement invariance across sex and between clinical (N = 313) and non-clinical (N = 341) samples.

Results

EFA supported a new four-factor structure with a motivation component, based on the original two-factor model (consummatory pleasure with/without motivation drive, anticipatory pleasure with/without motivation drive). CFA confirmed the four-factor model as the best-fit structure and revealed a second-order hierarchy in non-clinical and clinical samples. Full scalar invariance was observed across clinical and non-clinical samples and across sex in the clinical sample; only partial scalar invariance was observed across sex in the non-clinical sample.

Conclusions

A four-factor structured TEPS can assess motivation-driving dimensions of anticipatory and consummatory pleasure, consistent with the recently advanced multidimensional structure of anhedonia. CFA and measurement invariance results support application of the TEPS for assessing motivation aspects of anhedonia.
The impact of out-of pocket payments of households for dental healthcare services on catastrophic healthcare expenditure in Iran
Authors: Woldemichael Abraha , Rezaei Satar , Kazemi Karyani Ali , Ebrahimi Mohammad , Soltani Shahin , Aghaei Abbas
Published: July 2021

Background

Dental healthcare is the costliest and single most source of the financial barrier to seeking and use of needed healthcare. Hence, this study aims to analyses impact of out-of-pocket (OOP) payments for dental services on prevalence catastrophic healthcare expenditure (CHE) among Iranian households during 2018.

Methods

We performed a cross-sectional analysis to determine the prevalence rate of CHE due to use of dental healthcare services among 38,858 Iranian households using the 2018 Household Income and Expenditure Survey (HIES) survey data of Iran. The WHO approach was used to determine the CHE due to use of dental care services at the 40% of household capacity to pay (CTP). Multiple logistic regression models were used to obtain the odds of facing with CHE among households that paid for any dental healthcare services over the last month while adjusting for covariates included in the model. These findings were reported for urban, rural areas and also for low, middle and high human development index HDI across provinces.

Results

The study indicated that the prevalence of CHE among households that used and did not used dental services over the last month was 16.5% (95% CI: 14.9 to 18.3) and 4.3% (95% CI: 4.1 to 4.6), respectively. The adjusted odds ratio (AOR) for the covariates revealed that the prevalence of CHE for the overall households that used dental healthcare service was 6.2 times (95% CI: 5.4 to 7.1) than those that did not use dental healthcare services. The urban households that used dental healthcare had 7.8 times (95%CI: 6.4–9.4) while the rural ones had 4.7 times (95% CI: 3.7–5.7) higher odds of facing CHE than the corresponding households that did not use dental healthcare services.

Conclusions

The study indicates that out-of-pocket costs for dental care services impose a substantial financial burden on household’s budgets at the national and subnational levels. Alternative health care financing strategies and policies targeted to the reduction in CHE in general and CHE due to dental services in particular are urgently required in low and middle income countries such as Iran.
Health workers’ perceptions on where and how to integrate tobacco use cessation services into tuberculosis treatment; a qualitative exploratory study in Uganda
Authors: Rutebemberwa Elizeus , Nyamurungi Kellen , Joshi Surabhi , Olando Yvonne , Mamudu Hadii M. , Pack Robert P.
Published: July 2021

Background

Tobacco use is associated with exacerbation of tuberculosis (TB) and poor TB treatment outcomes. Integrating tobacco use cessation within TB treatment could improve healing among TB patients. The aim was to explore perceptions of health workers on where and how to integrate tobacco use cessation services into TB treatment programs in Uganda.

Methods

Between March and April 2019, nine focus group discussions (FGDs) and eight key informant interviews were conducted among health workers attending to patients with tuberculosis on a routine basis in nine facilities from the central, eastern, northern and western parts of Uganda. These facilities were high volume health centres, general hospitals and referral hospitals. The FGD sessions and interviews were tape recorded, transcribed verbatim and analysed using content analysis and the Chronic Care Model as a framework.

Results

Respondents highlighted that just like TB prevention starts in the community and TB treatment goes beyond health facility stay, integration of tobacco cessation should be started when people are still healthy and extended to those who have been healed as they go back to communities. There was need to coordinate with different organizations like peers, the media and TB treatment supporters. TB patients needed regular follow up and self-management support for both TB and tobacco cessation. Patients needed to be empowered to know their condition and their caretakers needed to be involved. Effective referral between primary health facilities and specialist facilities was needed. Clinical information systems should identify relevant people for proactive care and follow up. In order to achieve effective integration, the health system needed to be strengthened especially health worker training and provision of more space in some of the facilities.

Conclusions

Tobacco cessation activities should be provided in a continuum starting in the community before the TB patients get to hospital, during the patients’ interface with hospital treatment and be given in the community after TB patients have been discharged. This requires collaboration between those who carry out health education in communities, the TB treatment supporters and the health workers who treat patients in health facilities.
Onset of effects of non-pharmaceutical interventions on COVID-19 infection rates in 176 countries
Authors: Nader Ingo W. , Zeilinger Elisabeth L. , Jomar Dana , Zauchner Clemens
Published: July 2021

Background

During the initial phase of the global COVID-19 outbreak, most countries responded with non-pharmaceutical interventions (NPIs). In this study we investigate the general effectiveness of these NPIs, how long different NPIs need to be in place to take effect, and how long they should be in place for their maximum effect to unfold.

Methods

We used global data and a non-parametric machine learning model to estimate the effects of NPIs in relation to how long they have been in place. We applied a random forest model and used accumulated local effect (ALE) plots to derive estimates of the effectiveness of single NPIs in relation to their implementation date. In addition, we used bootstrap samples to investigate the variability in these ALE plots.

Results

Our results show that closure and regulation of schools was the most important NPI, associated with a pronounced effect about 10 days after implementation. Restrictions of mass gatherings and restrictions and regulations of businesses were found to have a more gradual effect, and social distancing was associated with a delayed effect starting about 18 days after implementation.

Conclusions

Our results can inform political decisions regarding the choice of NPIs and how long they need to be in place to take effect.
Gaps and opportunities for cervical cancer prevention, diagnosis, treatment and care: evidence from midterm review of the Zimbabwe cervical Cancer prevention and control strategy (2016–2020)
Authors: Tapera Oscar , Nyakabau Anna M. , Simango Ndabaningi , Guzha Bothwell T. , Jombo-Nyakuwa Shamiso , Takawira Eunice , Mapanga Angeline , Makosa Davidzoyashe , Madzima Bernard
Published: July 2021

Background

Cervical cancer is the fourth most common cancer amongst women globally and it accounts for the majority of cancer deaths among females in Zimbabwe. The objective of this midterm review analysis was to identify the gaps and opportunities for cervical cancer prevention, diagnosis, treatment, and care to inform the next cervical cancer strategy in Zimbabwe.

Methods

A mixed methods approach was used for the midterm review. Secondary data was collected from programme documents, published and grey literature. Primary data was collected in six provinces through key informant interviews with officials and focus group discussions with beneficiaries. After data analysis, a draft report was presented to a technical working group to validate the findings and to fill in any gaps.

Results

This midterm review revealed a myriad of gaps of the strategy particularly in diagnosis, treatment and care of cervical cancer and the primary focus was on secondary prevention. There was no data to quantify the level of awareness and advocacy for cervical cancer prevention. Our results revealed that there was no data on the proportion of women who ever tested for cervical cancer which existed nationally. Our findings suggest that some health facilities were screening women above 50 years old using VIAC, which is an inappropriate approach for those women. Quality control of VIAC and treatment of precancers were not part of the strategy. Pathological services were not efficient and effective due to lack of resources and additionally data on investigations were not routinely collected and available at the national level. Other gaps identified were limited funding, human resources, equipment, and commodities as well as lack of leadership at the national level to coordinate the various components of the cervical cancer programme. There are also numerous opportunities identified to build upon some successes realized to date.

Conclusions

Our findings emphasized the importance of effective and holistic planning in cervical cancer screening programmes in low-resource settings. In addition, huge investments are required in cervical cancer programmes and governments need to take centre role in mobilizing the requisite resources.
Young adults understanding and readiness to engage with palliative care: extending the reach of palliative care through a public health approach: a qualitative study
Authors: Mallon Anita , Hasson Felicity , Casson Karen , Slater Paul , McIlfatrick Sonja
Published: July 2021

Background

Moving palliative care from a solely clinical focus to a more population based and community orientated approach is the hallmark of a much advocated public health approach to palliative care. Young adults are a vital cohort of the public, yet their understanding of palliative care has not been investigated. This study aimed to explore young adults’ understanding of palliative care and identify factors that influence their engagement.

Methods

A purposive sample of young adults (n = 24) aged 18–29 years were recruited from one UK University. Semi-structured interviews were undertaken face to face or via telephone or Skype between November 2017 and February 2018. Thematic analysis using a framework approach and underpinned by a socioecological perspective was used to analyse the interviews.

Results

Three thematic categories were identified relating to intrapersonal and interpersonal influences, cultural and social influences and organisational and public policy influences. Palliative care was understood as supportive comfort care, delivered in the absence of cure, associated with the end of life and specifically focused on death and dying. Negative attitudes related to the context of care, which represented a static and hopeless situation. Whilst some reported positive attitudes, potential engagement was seen to be governed by a lack of knowledge and protective cultural norms. In terms of demonstrating readiness to engage with palliative care, participants requested clear information and suggested a normalising of palliative care through the education system.

Conclusion

Young adults in this study were ready to find out more about palliative care and identified social media as a platform upon which to engage this population. However, their perception of a society that views palliative care as a subject for those directly affected, creates a barrier to engagement. This study identified the ingredients of a public health message and mediums for disseminating the message. However, findings also suggest that a cultural shift is required to recognise the potential of engaging young adults in health issues that cross the life span, empowering them not only as individuals but as vital members of community and society.
Development and validation of teacher and student questionnaires measuring inhibitors of curriculum viability
Authors: Khan Rehan Ahmed , Spruijt Annemarie , Mahboob Usman , Al Eraky Mohamed , van Merrienboer Jeroen J. G.
Published: July 2021

Background

Curriculum viability is determined by the degree to which quality standards have or have not been met, and by the inhibitors that affect attainment of those standards. The literature reports many ways to evaluate whether a curriculum reaches its quality standards, but less attention is paid to the identification of viability inhibitors in different areas of the curriculum that hamper the attainment of quality. The purpose of this study is to develop and establish the reliability and validity of questionnaires that measure the presence of inhibitors in an undergraduate medical curriculum.

Methods

Teacher and student questionnaires developed by the authors were sent to medical educationalists for qualitative expert validation and to establish their content validity. To establish the response process validity, cognitive interviews were held with teachers and students to clarify any confusion about the meaning of items in the questionnaires. Reliability and construct validity of the questionnaires were established by responses from 575 teachers and 247 final-year medical students.

Results

Qualitative expert validation was provided by 21 experts. The initial teacher and student questionnaires containing respectively 62 items to measure 12 theoretical constructs, and 28 items to measure 7 constructs, were modified to improve their clarity and relevance. The overall scale validity index for the questionnaires was, in order, .95 and .94. Following the cognitive interviews, the resultant teacher and student questionnaires were reduced to respectively 52 and 23 items. Furthermore, after the confirmatory analysis, the final version of the teacher questionnaire was reduced to 25 items to measure 6 constructs and the student questionnaire was reduced to 14 items to measure 3 constructs. Good-for-fit indices were established for the final model and Cronbach alphas of, in order, .89 and .81 were found for the teacher and student questionnaire.

Conclusion

The valid and reliable curriculum viability inhibitor questionnaires for teachers and students developed in this study can be used by medical schools to identify inhibitors to achieve standards in different areas of the curriculum.
Barriers and facilitators to recognize and discuss depression and anxiety experienced by adults with vision impairment or blindness: a qualitative study
Authors: van Munster Edine P. J. , van der Aa Hilde P. A. , Verstraten Peter , van Nispen Ruth M. A.
Published: July 2021

Background

Depression and anxiety are highly prevalent, but often unrecognized in adults with vision impairment (VI) or blindness. The purpose of this study was to explore visually impaired and blind adults’ views on facilitators and barriers in recognizing and discussing mental health problems.

Methods

Semi-structured interviews, based on the Integrated Model for Change, were conducted with 16 visually impaired or blind adults receiving support from three Dutch low vision service organizations. Interview data was analyzed using the framework approach.

Results

Participants perceived their focus on practical support with regard to their VI, lack of mental health literacy, and misattribution of symptoms of depression or anxiety as barriers for recognizing mental health problems. With regard to discussing mental health problems, they perceived difficulties in acknowledging their VI and mental health problems due to feelings of vulnerability and inequality. Participants mentioned that their social support system and healthcare providers (could) facilitate them in recognizing and discussing mental health problems. However, participants thought that healthcare providers currently often lacked the knowledge, skills and attitude to recognize and discuss this topic with their clients.

Conclusion

Our findings suggest that visually impaired and blind adults may experience several barriers to recognize, acknowledge and discuss mental health. Healthcare providers and social support systems seem essential for them in reducing these barriers. However, there might be a mismatch between the needs of visually impaired and blind adults and healthcare providers’ knowledge, skills and attitude. Training healthcare providers may improve detection of depression and anxiety in adults with VI or blindness, and enhance clinician-patient communication on mental health.
Triglyceride-rich lipoprotein and LDL particle subfractions and their association with incident type 2 diabetes: the PREVEND study
Authors: Sokooti Sara , Flores-Guerrero Jose L. , Heerspink Hiddo J. L. , Connelly Margery A. , Bakker Stephan J. L. , Dullaart Robin P. F.
Published: July 2021

Background

Triglyceride-rich lipoproteins particles (TRLP) and low density lipoprotein particles (LDLP) vary in size. Their association with β-cell function is not well described. We determined associations of TRLP and LDLP subfractions with β-cell function, estimated as HOMA-β, and evaluated their associations with incident T2D in the general population.

Methods

We included 4818 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline. TRLP and LDLP subfraction concentrations and their average sizes were measured using the LP4 algorithm of the Vantera nuclear magnetic resonance platform. HOMA-IR was used as measure of insulin resistance. HOMA-β was used as a proxy of β-cell function.

Results

In subjects without T2D at baseline, very large TRLP, and LDL size were inversely associated with HOMA-β, whereas large TRLP were positively associated with HOMA-β when taking account of HOMA-IR. During a median follow-up of 7.3 years, 263 participants developed T2D. In multivariable-adjusted Cox regression models, higher concentrations of total, very large, large, and very small TRLP (reflecting remnants lipoproteins) and greater TRL size were associated with an increased T2D risk after adjustment for relevant covariates, including age, sex, BMI, HDL-C, HOMA-β, and HOMA-IR. On the contrary, higher concentrations of large LDLP and greater LDL size were associated with a lower risk of developing T2D.

Conclusions

Specific TRL and LDL particle characteristics are associated with β-cell function taking account of HOMA-IR. Moreover, TRL and LDL particle characteristics are differently associated with incident T2D, even when taking account of HOMA-β and HOMA-IR.
A molecular signature for the metabolic syndrome by urine metabolomics
Authors: Bruzzone Chiara , Gil-Redondo Rubén , Seco Marisa , Barragán Rocío , de la Cruz Laura , Cannet Claire , Schäfer Hartmut , Fang Fang , Diercks Tammo , Bizkarguenaga Maider , González-Valle Beatriz , Laín Ana , Sanz-Parra Arantza , Coltell Oscar , de Letona Ander López , Spraul Manfred , Lu Shelly C. , Buguianesi Elisabetta , Embade Nieves , Anstee Quentin M. , Corella Dolores , Mato José M. , Millet Oscar
Published: July 2021

Background

Metabolic syndrome (MetS) is a multimorbid long-term condition without consensual medical definition and a diagnostic based on compatible symptomatology. Here we have investigated the molecular signature of MetS in urine.

Methods

We used NMR-based metabolomics to investigate a European cohort including urine samples from 11,754 individuals (18–75 years old, 41% females), designed to populate all the intermediate conditions in MetS, from subjects without any risk factor up to individuals with developed MetS (4–5%, depending on the definition). A set of quantified metabolites were integrated from the urine spectra to obtain metabolic models (one for each definition), to discriminate between individuals with MetS.

Results

MetS progression produces a continuous and monotonic variation of the urine metabolome, characterized by up- or down-regulation of the pertinent metabolites (17 in total, including glucose, lipids, aromatic amino acids, salicyluric acid, maltitol, trimethylamine N-oxide, and p-cresol sulfate) with some of the metabolites associated to MetS for the first time. This metabolic signature, based solely on information extracted from the urine spectrum, adds a molecular dimension to MetS definition and it was used to generate models that can identify subjects with MetS (AUROC values between 0.83 and 0.87). This signature is particularly suitable to add meaning to the conditions that are in the interface between healthy subjects and MetS patients. Aging and non-alcoholic fatty liver disease are also risk factors that may enhance MetS probability, but they do not directly interfere with the metabolic discrimination of the syndrome.

Conclusions

Urine metabolomics, studied by NMR spectroscopy, unravelled a set of metabolites that concomitantly evolve with MetS progression, that were used to derive and validate a molecular definition of MetS and to discriminate the conditions that are in the interface between healthy individuals and the metabolic syndrome.
Cardiopulmonary alterations by ultrasound in a patient with uncomplicated mixed malaria infection: a case report from the Amazon Basin
Authors: Wegener Alma , Lima Karine O. , Holm Anna E. , Gomes Laura C. , Matos Luan O. , Vieira Isabelle V. M. , Souza Rodrigo Medeiros , Marinho Claudio Romero Farias , Vestergaard Lasse S. , Biering-Sørensen Tor , Silvestre Odilson M. , Brainin Philip
Published: July 2021

Background

Information on cardiopulmonary complications in clinical malaria is sparse and diagnosis may be difficult in resource-limited areas due to lack of proper diagnostic tools and access to medical care. A case of pericardial effusion and pulmonary alterations assessed by ultrasound in a patient with uncomplicated mixed malaria infection is described.

Case presentation

A previously healthy 23-year-old male from the Amazon Basin was diagnosed with mixed infection of Plasmodium vivax and Plasmodium falciparum by peripheral blood smear. The patient presented with mild malaria symptoms without signs of severe malaria, but reported moderate chest pain and shortness of breath. Laboratory analyses revealed thrombocytopenia and anemia. The electrocardiogram had PR depressions and bedside ultrasound of the cardiopulmonary system showed pericardial effusion (18 mm) accompanied by multiple B-lines in the lungs, identified as vertical artifacts extending from the pleural line. Cardiac biomarkers were normal. The patient was treated according to national guidelines for malaria and suspected pericarditis, respectively. At follow-up on day 5, the pericardial effusion (9mm) and B-lines had markedly decreased. By day 21 the patient was asymptomatic, had completed the treatment, and the electrocardiogram and ultrasound findings had normalized.

Conclusions

This case report highlight the usefulness of bedside ultrasound to identify cardiopulmonary involvement in patients with uncomplicated malaria and relevant symptoms.
PfHRP2 detection using plasmonic optrodes: performance analysis
Authors: Loyez Médéric , Wells Mathilde , Hambÿe Stéphanie , Hubinon François , Blankert Bertrand , Wattiez Ruddy , Caucheteur Christophe
Published: July 2021

Background

Early malaria diagnosis and its profiling require the development of new sensing platforms enabling rapid and early analysis of parasites in blood or saliva, aside the widespread rapid diagnostic tests (RDTs).

Methods

This study shows the performance of a cost-effective optical fiber-based solution to target the presence of Plasmodium falciparum histidine-rich protein 2 (PfHRP2). Unclad multimode optical fiber probes are coated with a thin gold film to excite Surface Plasmon Resonance (SPR) yielding high sensitivity to bio-interactions between targets and bioreceptors grafted on the metal surface.

Results

Their performances are presented in laboratory conditions using PBS spiked with growing concentrations of purified target proteins and within in vitro cultures. Two probe configurations are studied through label-free detection and amplification using secondary antibodies to show the possibility to lower the intrisic limit of detection.

Conclusions

As malaria hits millions of people worldwide, the improvement and multiplexing of this optical fiber technique can be of great interest, especially for a future purpose of using multiple receptors on the fiber surface or several coated-nanoparticles as amplifiers.
Health-related quality of life and physical activity in children with inherited cardiac arrhythmia or inherited cardiomyopathy: the prospective multicentre controlled QUALIMYORYTHM study rationale, design and methods
Authors: Amedro Pascal , Werner Oscar , Abassi Hamouda , Boisson Aymeric , Souilla Luc , Guillaumont Sophie , Calderon Johanna , Requirand Anne , Vincenti Marie , Pommier Victor , Matecki Stefan , De La Villeon Gregoire , Lavastre Kathleen , Lacampagne Alain , Picot Marie-Christine , Beyler Constance , Delclaux Christophe , Dulac Yves , Guitarte Aitor , Charron Philippe , Denjoy-Urbain Isabelle , Probst Vincent , Baruteau Alban-Elouen , Chevalier Philippe , Di Filippo Sylvie , Thambo Jean-Benoit , Bonnet Damien , Pasquie Jean-Luc
Published: July 2021

Background

Advances in paediatric cardiology have improved the prognosis of children with inherited cardiac disorders. However, health-related quality of life (QoL) and physical activity have been scarcely analysed in children with inherited cardiac arrhythmia or inherited cardiomyopathy. Moreover, current guidelines on the eligibility of young athletes with inherited cardiac disorders for sports participation mainly rely on expert opinions and remain controversial.

Methods

The QUALIMYORYTHM trial is a multicentre observational controlled study. The main objective is to compare the QoL of children aged 6 to 17 years old with inherited cardiac arrhythmia (long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, or arrhythmogenic right ventricular dysplasia), or inherited cardiomyopathy (hypertrophic, dilated, or restrictive cardiomyopathy), to that of age and gender-matched healthy subjects. The secondary objective is to assess their QoL according to the disease’s clinical and genetic characteristics, the level of physical activity and motivation for sports, the exercise capacity, and the socio-demographic data. Participants will wear a fitness tracker (ActiGraph GT3X accelerometer) for 2 weeks. A total of 214 children are required to observe a significant difference of 7 ± 15 points in the PedsQL, with a power of 90% and an alpha risk of 5%.

Discussion

After focusing on the survival in children with inherited cardiac disorders, current research is expanding to patient-reported outcomes and secondary prevention. The QUALIMYORYTHM trial intends to improve the level of evidence for future guidelines on sports eligibility in this population.

Trial registrationClinicalTrials.gov Identifier: NCT04712136, registered on January 15th, 2021 (https://clinicaltrials.gov/ct2/show/NCT04712136).
Pterostilbene alleviates pulmonary fibrosis by regulating ASIC2
Authors: Peng Yanfang , Zhang Yingwen , Zhang Yabing , Wang Xiuping , Xia Yukun
Published: July 2021

Background

Idiopathic pulmonary fibrosis (IPF) is a serious chronic disease of the respiratory system, but its current treatment has certain shortcomings and adverse effects. In this study, we evaluate the antifibrotic activity of pterostilbene (PTE) using an in vitro IPF model induced by transforming growth factor (TGF)-β1.

Methods

A549 and alveolar epithelial cells (AECs) were incubated with 10 ng/ml TGF-β1 to induce lung fibroblast activation. Then, 30 μmol/L of PTE was used to treat these cells. The epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and autophagy in cells were evaluated by western blot. Apoptosis was validated by flow cytometry analysis and western blot. Transcriptome high-throughput sequencing was performed on A549 cells incubated with TGF-β1 alone or TGF-β1 and PTE (TGF-β1 + PTE), and differentially expressed genes in PTE-treated cells were identified. The acid sensing ion channel subunit 2 (ASIC2) overexpression plasmid was used to rescue the protein levels of ASIC2 in A549 and AECs.

Results

TGF-β1 caused EMT and ECM accumulation, and blocked the autophagy and apoptosis of A549 and AECs. Most importantly, 30 μmol/L of PTE inhibited pulmonary fibrosis induced by TGF-β1. Compared with TGF-β1, PTE inhibited EMT and ECM accumulation and rescued cell apoptosis and autophagy. The results of transcriptome high-throughput sequencing revealed that PTE greatly reduced the protein level of ASIC2. Compared with the TGF-β1 + PTE group, the transfection of ASIC2 overexpression plasmid stimulated the EMT and ECM accumulation and inhibited apoptosis and autophagy, suggesting that PTE inhibited pulmonary fibrosis by downregulating ASIC2.

Conclusions

This study suggests that PTE and ASIC2 inhibitors may have potential as IPF treatments in the future.
Improving lung compliance by external compression of the chest wall
Authors: Marini John J. , Gattinoni Luciano
Published: July 2021

As exemplified by prone positioning, regional variations of lung and chest wall properties provide possibilities for modifying transpulmonary pressures and suggest that clinical interventions related to the judicious application of external pressure may yield benefit. Recent observations made in late-phase patients with severe ARDS caused by COVID-19 (C-ARDS) have revealed unexpected mechanical responses to local chest wall compressions over the sternum and abdomen in the supine position that challenge the clinician’s assumptions and conventional bedside approaches to lung protection. These findings appear to open avenues for mechanism-defining research investigation with possible therapeutic implications for all forms and stages of ARDS.
Effectiveness and safety of a simple home-based rehabilitation program in pulmonary arterial hypertension: an interventional pilot study
Authors: Wojciuk Mariusz , Ciolkiewicz Mariusz , Kuryliszyn-Moskal Anna , Chwiesko-Minarowska Sylwia , Sawicka Emilia , Ptaszynska-Kopczynska Katarzyna , Kaminski Karol
Published: July 2021

Background

Rehabilitation plays an important role in the management of patients with pulmonary arterial hypertension (PAH) and current guidelines recommend implementation of a monitored individualized exercise training program as adjuvant therapy for stable PAH patients on optimal medical treatment. An optimal rehabilitation model for this group of patients has not yet been established. This randomized prospective study assessed the effectiveness and safety of a 6-month home-based caregiver-supervised rehabilitation program among patients with pulmonary arterial hypertension.

Methods

A total of 39 patients with PAH were divided into two groups: intervention group (16 patients), subjected to a 6-month home-based physical training and respiratory rehabilitation program adapted to the clinical status of participants, and control group (23 patients) who did not perform physical training. The 6-min walk test (6MWT), measurement of respiratory muscle strength, quality of life assessment (SF-36, Fatigue Severity Scale – FSS) were performed before study commencement, and after 6 and 12 months. Adherence to exercise protocol and occurrence of adverse events were also assessed.

Results

Physical training significantly improved 6MWT distance (by 71.38 ± 83.4 m after 6 months (p = 0.004), which remained increased after 12 months (p = 0.043), and respiratory muscle strength after 6 and 12 months (p < 0.01). Significant improvement in quality of life was observed after the training period with the use of the SF-36 questionnaire (Physical Functioning, p < 0.001; Role Physical, p = 0.015; Vitality, p = 0.022; Role Emotional, p = 0.029; Physical Component Summary, p = 0.005), but it did not persist after study completion. Adherence to exercise protocol was on average 91.88 ± 14.1%. No serious adverse events were noted.

Conclusion

According to study results, the home-based rehabilitation program dedicated to PAH patients is safe and effective. It improves functional parameters and quality of life. Strength of respiratory muscles and 6MWD remain increased 6 months after training cessation.

Trial registration

ClinicalTrials.gov, NCT03780803. Registered 12 December 2018
Preoperative walking recommendation for non-cardiac surgery patients to reduce the length of hospital stay: a randomized control trial
Authors: Cortés Olga L. , Herrera-Galindo Mauricio , Becerra Claudia , Rincón-Roncancio Mónica , Povea-Combariza Camilo , Esparza-Bohorquez Maribel
Published: July 2021

Background

Even though the importance of preparing patients for a surgical event is recognized, there are still gaps about the benefit of improving functional capacity by walking during the waiting time among patients scheduled for non-cardiac surgery. The aim of this study was to evaluate the impact of pre-surgical walking in-hospital length of stay, early ambulation, and the appearance of complications after surgery among patients scheduled for non-cardiac surgery.

Methods

A two-arm, single- blinded randomized controlled trial was developed from May 2016 to August 2017. Eligible outpatients scheduled for non-cardiac surgery, capable of walking, were randomized (2:1 ratio) to receive a prescription of walking 150 min/week during the whole pre-surgical waiting time (n = 249) or conventional care (n = 119). The primary outcome was the difference in hospital length of stay, and secondary results were time to first ambulation during hospitalization, description of ischemic events during hospitalization and after six months of hospital discharge, and the walking continuation. We performed an intention to treat analysis and compared length of stay between both groups by Kaplan–Meier estimator (log-rank test).

Results

There were no significant differences in the length of hospital stay between both groups (log-rank test p = 0.367) and no differences in the first ambulation time during hospitalization (log-rank test p = 0.299). Similar rates of postoperative complications were observed in both groups, but patients in the intervention group continued to practice walking six months after discharge (p < 0.001).

Conclusion

Our study is the first clinical trial evaluating the impact of walking before non-cardiac surgery in the length of stay, early ambulation, and complications after surgery. Prescription of walking for patients before non-cardiac surgery had no significant effect in reducing the length of stay, and early ambulation. The results become a crucial element for further investigation.

Trial registration: PAMP-Phase2 was registered in ClinicalTrials.gov NCT03213496 on July 11, 2017.
Plurihormonal pituitary macroadenoma: a case report
Authors: Allehaibi Ebtesam , AlMalki Mussa H. , Brema Imad
Published: July 2021

Background

Plurihormonal pituitary adenomas are a unique type of pituitary adenomas that secrete two or more pituitary hormones normally associated with separate cell types that have different immunocytochemical and ultrastructural features. Although they represent 10–15% of all pituitary tumors, only a small fraction of plurihormonal pituitary adenomas clinically secrete multiple hormones. The most common hormone combinations secreted by plurihormonal pituitary adenomas are growth hormone, prolactin, and one or more glycoprotein hormones. The most common hormonal symptom is acromegaly (50%). The aim of this case report is to bring awareness about this rare type of pituitary adenomas and to describe the unique presentation of our patient, even though plurihormonal pituitary adenomas are known mostly as a clinically silent tumors.

Case presentation

Herein, we describe an unusual case of plurihormonal pituitary adenoma with triple-positive staining for adrenocorticotropic hormone, growth hormone, and prolactin. The patient is a 65-year-old Egyptian woman who presented with mass effect symptoms of the pituitary tumor, which primarily manifested as severe headache and visual field defects. She also presented with some cushingoid features, and further analysis confirmed Cushing’s disease; slightly high prolactin and normal growth hormone levels were observed. She underwent transsphenoidal surgery and has been in remission thus far. Only a few cases have been reported in the literature, but none has exhibited silent acromegaly or mass effect symptoms as the initial presentation.

Conclusion

This case highlights an unusual plurihormonal pituitary adenoma case with a rare combination of secreted hormones; mass effect symptoms were dominant, as were uncommon visual field defects. Our case further proves that immunohistochemical analyses of all pituitary hormones are needed to ensure correct diagnosis and to alert clinicians to the need for more rigorous follow-up due to the higher morbidity of these patients. Our case report approval number Federal Wide Assurance NIH, USA is FWA00018774 IRB registration number with OHRP/NIH is IRB00010471.