bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Multiple Re-Entry Tears in Type B Aortic Dissection Progression: A Longitudinal Study Using a Controlled Swine Model
Authors: Armour Chlöe , Guo Baolei , Saitta Simone , Guo Daqiao , Liu Yifan , Fu Weiguo , Dong Zhihui , Xu Xiao Yun
Published: July 2022

Purpose:

False lumen (FL) expansion often occurs in type B aortic dissection (TBAD) and has been associated with the presence of re-entry tears. This longitudinal study aims to elucidate the role of re-entry tears in the progression of TBAD using a controlled swine model, by assessing aortic hemodynamics through combined imaging and computational modeling.

Materials and Methods:

A TBAD swine model with a primary entry tear at 7 cm distal to the left subclavian artery was created in a previous study. In the current study, reintervention was carried out in this swine model to induce 2 additional re-entry tears of approximately 5 mm in diameter. Computed tomography (CT) and 4-dimensional (4D) flow magnetic resonance imaging (MRI) scans were taken at multiple follow-ups before and after reintervention. Changes in aortic volume were measured on CT scans, and hemodynamic parameters were evaluated based on dynamic data acquired with 4D-flow MRI and computational fluid dynamics simulations incorporating all available in vivo data.

Results:

Morphological analysis showed FL growth of 20% following the initial TBAD—growth stabilized after the creation of additional tears and eventually FL volume reduced by 6%. Increasing the number of re-entry tears from 1 to 2 caused flow redistribution, with the percentage of true lumen (TL) flow increasing from 56% to 78%; altered local velocities; reduced wall shear stress surrounding the tears; and led to a reduction in FL pressure and pressure difference between the 2 lumina.

Conclusion:

This study combined extensive in vivo imaging data with sophisticated computational methods to show that additional re-entry tears can alter dissection hemodynamics through redistribution of flow between the TL and FL. This helps to reduce FL pressure, which could potentially stabilize aortic growth and lead to reversal of FL expansion. This work provides a starting point for further study into the use of fenestration in controlling undesirable FL expansion.

Clinical Impact

Aortic growth and false lumen (FL) patency are associated with the presence of re-entry tears in type B aortic dissection (TBAD) patients. Guidelines on how to treat re-entry tears are lacking, especially with regards to the control and prevention of FL expansion. Through a combined imagining and computational hemodynamics study of a controlled swine model, we found that increasing the number of re-entry tears reduced FL pressure and cross lumen pressure difference, potentially stabilising aortic growth and leading to FL reduction. Our findings provide a starting point for further study into the use of fenestration in controlling undesirable FL expansion.
Challenges and Successes During the Early Years of the Nsukka Music School
Authors: Ogisi Arugha A.
Published: July 2022

Nigeria’s triple music heritage of traditional, Islamic and Western music should have informed her formal music education curriculum. Instead, western music was used by the early Christian missionaries that it became difficult to integrate indigenous music traditions into the curriculum that music could not gain traction as a school subject across the country. In an effort to correct the defect a bi-musical curriculum of western and African traditional music was designed by the Nsukka Music School (NMS). Although the change was epistemologically right, the bi-musical curriculum confronted numerous challenges during implementation. This paper identifies the challenges and discusses how they were addressed. Data were obtained through interviews of key informants and a review of relevant literature. The challenge of stereotyping music and musicians was solved by students proving their mettle among their peers. Non-acceptance of music within the academia and society, was not addressed throughout the period. Difficulty of finding music lecturers was ameliorated by employing expatriates and some Nigerians but the latter undertook graduate studies abroad. Lack of scholars and traditional practitioners in the theoretical and practical aspects of African music knowledge was solved through awarding research grants for traditional African music, and hiring traditional musicians to teach indigenous instruments. Challenges arising from low student registration were ameliorated by creating alternative entry requirements for music while encouraging non-music majors to register for music ensemble courses. The challenge of poor musical background of the foundation music majors was tackled by passing them through an accelerated program and creating an enabling environment for teaching and learning. The solutions to the challenges enabled NMS to graduate students that were musically competent and socially relevant.
Mass shootings, fatality thresholds and defining by numbers: Political and social consequences
Authors: Watson Sarah
Published: July 2022

Mass shootings are one example of a focusing event that has particular significance for firearms legislation. Mass shootings shock, disturb and provoke enormous and controversial debate, often causing significant public and media resonance, becoming the subject of intense discussion politically. At times providing an impetus for legislative amendments, often in distinct ways that routine gun violence does not. If certain events highlight the need for reform, policy change becomes more likely. Cases with the lowest number of victims are likely to generate the least amount of attention and are most likely to be missed in data collection, rendering them the least noteworthy, least important in terms of lethality and social and political consequence. Various problems come to the attention of people in and around government, necessitating an understanding of why such problems occupy officials’ attention and appear to be more ‘deserving’ of attention.
The potential of GLP-1 receptor agonists in type 2 diabetes and chronic kidney disease: from randomised trials to clinical practice
Authors: von Scholten Bernt Johan , Kreiner Frederik Flindt , Rasmussen Søren , Rossing Peter , Idorn Thomas
Published: July 2022

Chronic kidney disease (CKD) affects around 10% of the global population and is most often caused by diabetes. Diabetes with CKD (diabetic kidney disease, DKD) is a progressive condition that may cause kidney failure and which contributes significantly to the excess morbidity and mortality in these patients. DKD is treated with direct disease-targeting therapies like blockers of the renin–angiotensin system, sodium–glucose cotransporter-2 (SGLT-2) inhibitors and non-steroidal mineralocorticoid receptor antagonists as well as indirect therapies impacting hyperglycaemia, dyslipidaemia, obesity and hypertension, which all together reduce disease progression. While no glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are currently indicated to improve kidney outcomes, accumulating evidence from cardiovascular outcomes trials (CVOTs) corroborates a kidney-protective effect in people with T2D and CKD, and GLP-1 RAs are now mentioned in international treatment guidelines for type 2 diabetes (T2D) with CKD. GLP-1 RAs are indicated to improve glycaemia in people with T2D; certain GLP-1 RAs are also approved for weight management and to reduce cardiovascular risk in T2D. Ongoing pivotal trials are assessing additional indications, including T2D with CKD. In this article, we review and discuss kidney outcomes from a multitude of completed clinical trials as well as real-world evidence and ongoing clinical trials.
Olanzapine long-acting injection, discontinuation rates and reasons for discontinuation: 10 years’ experience at a UK high-secure hospital
Authors: Attard Azizah , Wakelam John , Broyd Josephine , Taylor David , Hafferty Jonathan
Published: July 2022

Background:

Olanzapine pamoate has been shown to be an effective second-generation long-acting injection. Its popularity has possibly been adversely affected by the rare incidence of post-injection syndrome (PIS) and the associated requirement to monitor for 3 h after each injection.

Objective:

This study aimed to collect and present data on the use of olanzapine long-acting injection (OLAI) over a 10-year period in a high-security forensic hospital in South East England.

Design:

This was a non-interventional retrospective study collecting information from anonymised electronic patient and prescription records. As per hospital Trust guidelines, patient consent to access of hospital records was presumed unless explicitly withdrawn.

Method:

All patients prescribed OLAI between the years 2009 and 2019 were identified. Data collected included date that OLAI was started, stopped, dose range, side effects and concomitant medication.

Results:

Of 88 patients who were started OLAI, 45 (51%) continued at month 24. At 60 months, 22 of 70 (31%) patients for whom data were available continued with OLAI. Over 60% of continuers were on higher than recommended doses. Of almost 5000 injections administered, there was 1 episode of PIS.

Conclusion:

OLAI is an effective treatment for schizophrenia and schizoaffective disorder, especially when used in patients have been able to tolerate the drug and were stabilised on it for 24 months. In over half the patients who continued OLAI, the doses were higher than that recommended by the manufacturer. The incidence of PIS in this study was very low in comparison with other studies.

Registration code:

2049
Assisted Peritoneal Dialysis Implementation: A Pilot Program From a Large Dialysis Unit in Quebec
Authors: Melanson Julien , Kachmar Jessica , Laurin Louis-Philippe , Elftouh Naoual , Nadeau-Fredette Annie-Claire
Published: July 2022

Background:

Kidney failure prevalence is increasing in older patients for whom dialysis initiation can be challenging. Assisted peritoneal dialysis (PD), where PD is performed with the help of a healthcare worker, can facilitate PD for frailer patients who may not be candidate otherwise.

Objectives:

This study aimed to assess the feasibility of implementing the first pilot assisted PD program in Quebec (Canada) and to evaluate the characteristics and outcomes of the PD cohort before and after assisted PD availability.

Design:

Observational retrospective cohort study.

Setting and Population:

All adult patients initiating PD between 2015 and 2020 in a single-center dialysis unit were included.

Measurements:

Incidence, characteristics, and outcomes of patients with PD were compared between (1) the “pre” (2015-2017) and the “post” assisted PD era (2018-2020) and (2) patients with assisted PD and independent PD in the more recent period.

Methods:

The primary outcome was peritonitis rate over the first year. Secondary outcomes included hospitalization, transfers to in-center hemodialysis (HD) and mortality.

Results:

Overall, 124 patients initiated PD with an annual incidence of 17 ± 3 patients during the “pre” and 24 ± 8 patients during the “post” assisted PD era ( P = .18). First-year peritonitis rate was similar over the 2 eras. Years of PD initiation and use of assisted PD were not associated with risk peritonitis (over total follow-up) after adjustment. Adjusted hazard of transfer to HD or death was higher during the “post” era (hazard ratio [HR]: 2.77; 95% confidence interval [CI]: 1.42-5.58). Seventeen patients received assisted PD including 13 (18%) of the 72 patients initiated between 2018 and 2020. Patients with assisted PD were older than those with independent PD (72 [64-84] vs. 59 [47-67], P = .006) and received assistance for 0.8 (0.4-1.5) years. When comparing assisted and independent cohorts, there were no differences in crude rates of peritonitis or hospitalization.

Limitations:

Single-center study with small sample size.

Conclusion:

This study shows the feasibility of implementing an assisted PD program, with favorable overall outcomes including similar rates of peritonitis during the first year after PD initiation.
Circumstances Precipitating Rural Older Adults for Co-Residential Family Care Arrangements in Central Ethiopia
Authors: Mefteh Kidus Yenealem
Published: July 2022

This study aims to explore circumstances that precipitate rural older adults for co-residential family care arrangements employing a phenomenological study method. Data from in-depth interviews with 12 rural older adults were inductively coded and developed into themes. Physical limitations and health problems, separation and divorce, death of a spouse, economic problem, neglect, inheritance dispute, and inaccessible locations are the circumstances that precipitate older adults to give up their independent living and start living with their children in the study area. The study points out to policymakers and other concerned bodies that actions must be geared toward maintaining a positive living environment for rural older adults and tackling challenges that are decisive in co-residential family care setting. Increasing health care accessibility, expanding senior/adult care centers and community health insurance programs, training geriatric social workers, enhancing collaboration between family caregivers and formal services, and provision of assistive devices for debilitating health conditions and subsequent disability will enhance the quality of life of rural older adults in co-residential family care arrangement.
Why are Patient Portals Important in the Age of COVID-19? Reflecting on Patient and Team Experiences From a Toronto Hospital Network
Authors: Lo Brian , Charow Rebecca , Laberge Sarah , Bakas Vasiliki , Williams Laura , Wiljer David
Published: July 2022

The COVID-19 pandemic has changed how care is being delivered in Canada. With conventional in-person care being transitioned to virtual care, the approach that patients are able to engage and access their care has dramatically changed. At the University Health Network (UHN), which is Canada's largest academic and teaching hospital network, we expanded the myUHN Patient Portal in 2017 after its early adopter phase to enable patients and family members to view parts of their clinical notes and test results. As the pandemic progressed, we observed high adoption of myUHN to support virtual care and rapid delivery of COVID-19 test results in real time. In this article, we share and reflect on our experience of adapting myUHN to support the demands of the pandemic, including portal adoption outcomes across multiple waves of the pandemic, the impetus for increased patient experience staff dedicated for myUHN support, and patients’ perceptions of the value of the portal and virtual care. Based on these reflections, we outline our perspectives on the future role of patient portals to support patient care and experience in a post-pandemic environment.
The theory of school arithmetic: Fractions
Authors: Ma Liping , Kessel Cathy
Published: July 2022

In 1999, Liping Ma's study of US and Chinese elementary teachers’ mathematical knowledge presented readers with a puzzle. Why did the US teachers, all of whom had tertiary degrees and were enrolled in intensive post-graduate programs, show less knowledge of school mathematics than the Chinese teachers, who had so much less education? Why were the Chinese teachers able to connect procedural topics such as algorithms with conceptual topics such as place value and the distributive law? We believe that an important part of the explanation is that the school arithmetic in the two countries was profoundly different: Unlike the school arithmetic of their US counterparts, the solid substance of the school arithmetic learned and taught by the Chinese teachers afforded mathematical reasoning. We illustrate this claim and the meaning of “solid substance” by presenting a logical system distilled from 19th-century US and 20th-century Chinese elementary textbooks. This system extends the system described in our 2018 article “The Theory of School Arithmetic: Whole Numbers.”
Densification and health in China: A U-shaped association between population density and obesity
Authors: Sun Bindong , Yin Chun , Yao Xiajie
Published: July 2022

Densification is a key measure to improve public health in many low-density countries. However, empirical studies show that population density has mixed results on health in different contexts. A possible hypothesis is that the relationship between population density and unhealthiness is a U-shaped curve. This study tested the U-shaped relationship between population density and body mass index (BMI). It employed fixed effects models with longitudinal and nationwide data in China collected between 2012 and 2014, comprising 3,423 observations from 1,984 respondents. After controlling for individuals’ socioeconomic characteristics and other built environmental elements, the results support the hypothesis of the U-shaped association between population density and BMI. Specifically, when population density is low, it is negatively related to BMI. However, when population density is high, it has positive effects on BMI. We further discuss the possible mechanisms and thresholds of the U-shaped effects of population density. The U-shaped relationship between densification and obesity encourages planners to consider local contexts and adopt a moderate population density when planning healthy cities.
Algorithmic improvements for discovery of germline copy number variants in next-generation sequencing data
Authors: O’Fallon Brendan , Durtschi Jacob , Kellogg Ana , Lewis Tracey , Close Devin , Best Hunter
Published: July 2022

Background

Copy number variants (CNVs) play a significant role in human heredity and disease. However, sensitive and specific characterization of germline CNVs from NGS data has remained challenging, particularly for hybridization-capture data in which read counts are the primary source of copy number information.

Results

We describe two algorithmic adaptations that improve CNV detection accuracy in a Hidden Markov Model (HMM) context. First, we present a method for computing target- and copy number-specific emission distributions. Second, we demonstrate that the Pointwise Maximum a posteriori (PMAP) HMM decoding procedure yields improved sensitivity for small CNV calls compared to the more common Viterbi HMM decoder. We develop a prototype implementation, called Cobalt, and compare it to other CNV detection tools using sets of simulated and previously detected CNVs with sizes spanning a single exon to a full chromosome.

Conclusions

In both the simulation and previously detected CNV studies Cobalt shows similar sensitivity but significantly fewer false positive detections compared to other callers. Overall sensitivity is 80–90% for deletion CNVs spanning 1–4 targets and 90–100% for larger deletion events, while sensitivity is somewhat lower for small duplication CNVs.
Planning is not equivalent to preparing, how Dutch women perceive their pregnancy planning in relation to preconceptional lifestyle behaviour change - a cross-sectional study
Authors: Maas Veronique Y. F. , Poels Marjolein , de Kievit Marleen H. , Hartog Anniek P. , Franx Arie , Koster Maria P. H.
Published: July 2022

Background

Unhealthy prenatal lifestyle behaviours are associated with adverse pregnancy outcomes, but little is known about what motivates women to comply with preconceptional lifestyle recommendations or consciously plan their pregnancy. Therefore, the objective of this study is to explore the associations between preconceptional lifestyle behaviours, health beliefs and pregnancy planning among Dutch pregnant women.

Methods

In this cross-sectional study based on the data of the APROPOS-II study, 1,077 low-risk pregnant women were eligible for inclusion. Preconception lifestyle behaviours and actively preparing for pregnancy were assessed in relation to planned pregnancies (based on the London Measure of Unplanned Pregnancies) and health beliefs (14 statements). The following preconceptional lifestyle behaviours were assessed through a self-administered questionnaire in the first trimester of pregnancy: fruit intake, vegetable intake, caffeine intake, (second-hand)smoking, alcohol intake, folic acid supplement use and exercise. Data were analysed using multivariate logistic regression analyses.

Results

A total of 921 (85.5%) women in our cohort had a planned pregnancy. However, of these women, 640 (69.5%) adequately used folic acid supplements and 465 (50.5%) women consumed alcohol at any point during pregnancy. Of the women considering themselves ‘healthy enough and not needing preconception care’, 48 (9.1%) women had an adequate vegetable intake, 294 (55.6%) women consumed alcohol at any point during pregnancy and 161 (30.4%) women were either over-or underweight.

Conclusion

Despite consciously planning their pregnancy, most women did not adhere to preconceptional lifestyle behaviour recommendations. Women’s health beliefs and overestimation of their health status seem to interfere with actively planning and preparing for pregnancy. Findings from our study may encourage the development of prospective health-promoting interventions that focus on health beliefs and actively preparing for pregnancy, to improve preconceptional lifestyle behaviours, thereby optimizing the health of future generations.
Outcomes of serial sessions of Activa mask combined with intense pulsed light therapy in patients with Meibomian gland dysfunction
Authors: Vigo Luca , Pellegrini Marco , Carones Francesco , Scorcia Vincenzo , Giannaccare Giuseppe
Published: July 2022

Background

To evaluate the effects on ocular surface signs and symptoms of serial sessions of heating and vibrating eye mask followed by intense pulsed light (IPL) therapy for the treatment of dry eye disease owing to meibomian gland dysfunction (MGD).

Methods

Consecutive patients with MGD whose signs and symptoms were not satisfactorily controlled with conventional therapy were included. Patients received 3 treatments performed at day 1, 15, and 45 incorporating a session with a newly-developed eye mask (Activa, SBS Sistemi, Turin, Italy) immediately followed by IPL therapy (E > Eye device, E-Swin, Paris, France). Patients were examined before the first session (T0) and 30 days after the last session (T1) for the measurement of: noninvasive break-up time (NIBUT); lipid layer thickness (LLT); tear meniscus height (TMH); meibomian gland loss (MGL); tear osmolarity. Ocular discomfort symptoms were ascertained by ocular surface disease index (OSDI) questionnaire.

Results

Thirty patients were ultimately included in the study. At T1, all objective ocular surface parameters improved significantly, except for TMH: NIBUT and LLT increased from 6.4 ± 1.7 to 8.6 ± 1.7 s and from 57.7 ± 15.5 to 81.3 ± 12.0 μm (all P < 0.001), while MGL and tear osmolarity decreased from 21.1 ± 17.3 to 17.0 ± 14.1% and from 302.0 ± 8.5 to 295.7 ± 6.9 mOsm/L (respectively, P = 0.004 and P < 0.001). In parallel, OSDI score decreased significantly from 49.8 ± 13.5 to 29.8 ± 10.6 (P < 0.001). In the historical control group of patients who underwent only IPL, NIBUT, LLT, tear osmolarity and OSDI improved significantly but not MGL and TMH.

Conclusions

Serial sessions incorporating the application of an eye mask producing heating and vibration immediately followed by IPL therapy are able to improve all ocular surface parameters as well as ocular discomfort symptoms in MGD patients.
Developing good practice indicators to assist mental health practitioners to converse with young people about their online activities and impact on mental health: a two-panel mixed-methods Delphi study
Authors: Biddle Lucy , Rifkin-Zybutz Raphael , Derges Jane , Turner Nicholas , Bould Helen , Sedgewick Felicity , Gooberman-Hill Rachael , Moran Paul , Linton Myles-Jay
Published: July 2022

Background

Online activity has been linked to poor mental health in children and young people, particularly those with existing vulnerability who may inadvertently or otherwise access harmful content. It is suggested health and social care practitioners should address online activity during mental health consultations, but guidance about acceptable or effective ways to do this is lacking. This study sought to derive good practice guidance to support mental health practitioners to engage young people in conversations about their online activities and impact on mental health.

Methods

A mixed-methods Delphi (consensus) study was conducted with a panel of mental health practitioners (n = 21) and a panel of young people (n = 22). Practitioners worked with children or young adults in the UK, mostly in statutory services (80.9%), in varied clinical roles, with 2 – 30 years of experience and most were female (87.5%). Young people were mostly female (77.3%), 13—22 years old, reported varied mental health diagnoses and had sought help from services. Across 3 rounds, panellists completed questionnaires which involved rating agreement with statements and answering open-ended questions. Iterative analysis informed subsequent questionnaire content. The percentage of participants rating their level of agreement with each statement was calculated. The threshold for inclusion as a good practice indicator (GPI) was 75% across both panels. Thematic analysis was used for free-text data.

Results

Twenty-seven GPIs emerged covering ‘who’ (which young people) should be asked about online activities, ‘when’, ‘what’ should be discussed, and with what ‘outcome’. Panels agreed conversations should be initiated with all young people from first meeting and regularly thereafter, with ‘red flags’ indicating a conversation may be pertinent. Core topics were identified with additional areas for patients presenting with disordered eating or self-harm. Panels emphasised conversations should be fluid, normalised, and encourage reflection and self-awareness.

Conclusions

Mental health practitioners could empower young people to exercise agency in relation to online safety and capitalise on positive features. Findings also identify training needs for practitioners. Further research should explore real-world application of the GPIs and transferability to underrepresented groups within our panels, such as males and younger children. Ethnicity and deprivation were not recorded.
Results of the Cologne Corona surveillance (CoCoS) study – a prospective population-based cohort study: incidence data and potential underestimation of new SARS-CoV-2 adult infections by health authorities
Authors: Oberste Max , Pusch Lynn-Marie , Roth Rebecca , Shah-Hosseini Kija , Schmitz Jana , Heger Eva , Dewald Felix , Müller Claudia , von Goltzheim Luise Stach , Lehmann Clara , Buess Michael , Wolff Anna , Fätkenheuer Gerd , Wiesmüller Gerhard , Klein Florian , Rosenberger Kerstin Daniela , Neuhann Florian , Hellmich Martin
Published: July 2022

Background

Current incidence estimates of SARS-CoV-2 in Germany rely to a large extent on case notifications. However, the large number of mild or asymptomatic infections is likely to result in underestimation. Population-based studies can provide valid estimates of the SARS-CoV-2 incidence and thus support health authorities to monitor the epidemiological situation and to initiate, maintain, strengthen or relax effective countermeasures.

Methods

This study was conducted in Cologne, Germany. Six-thousand randomly drawn Cologne residents, 18 years of age or older, were contacted by mail in March 2021. Study envelopes contained a kit for self-administered saliva sample and access details to a questionnaire on sociodemographic characteristics, previous positive SARS-CoV-2 RT-qPCR and completed COVID-19 vaccinations. Participants were again invited for a second round in June 2021, while those who declined participation were replaced by additional randomly drawn Cologne residents in order to reach a total of 6000 potential participants again. The saliva samples were sent to the laboratory by mail and tested for SARS-CoV-2 using RT-qPCR. The incidence estimates were adjusted for sensitivity and specificity of the test procedure and compared with the official numbers of new SARS-CoV-2 cases in the adult Cologne population.

Results

The first surveillance round in March 2021 (response rate: 34.08%, N = 2045) showed a SARS-CoV-2 seven-day incidence of 85 cases per 100,000 adult Cologne residents (95% CI: 9 to 319). In the same period, the officially registered cases were 125 per 100,000. The second surveillance round in June 2021 (response rate: 36.53%, N = 2192) showed a seven-day incidence of 27 per 100,000 adult Cologne residents (95% CI: 1 to 142), while the official figures for newly registered SARS-CoV-2 cases in the same period were 15 per 100,000.

Conclusions

The incidence estimates do not indicate relevant underestimation of new SARS-CoV-2 infections based on case notification. Regular use of the surveillance method developed here may nevertheless complement the efforts of the health authorities to assess the epidemiological situation.

Trial registration

DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.
Validation of the severe respiratory insufficiency questionnaire for Chile
Authors: Andrade Marianela , Antolini Mónica , Canales Krishnna , Maquilon Cesar , Fuentes Mauricio , Mazzei Marinella
Published: July 2022

Background

Long-term home non-invasive ventilation (LTH-NIV) has an impact on the health-related quality of life of patients with chronic hypercapnic respiratory failure (CRF) of different causes. There are generic and specific questionnaires for respiratory diseases. In 2003 a specific questionnaire was developed for patients with CRF in LTH-NIV, called the Severe Respiratory Insufficiency (SRI) questionnaire, which has been shown to be reproducible and reliable and has been validated in several languages.

The aim of the study was to translate and culturally adapt the SRI questionnaire for adult Chilean patients under LTH-NIV, and to assess its psychometric properties.

Methods

The Chilean version of the SRI was obtained using the translation-back translation method, which was then applied by cross-sectional study to a non-probabilistic convenience sample of stable patients from five regions of Chile. The validated Chilean version of the SRI questionnaire and SF-36 (gold standard) questionnaire were applied, demographic and ventilatory data were collected. Reliability was analysed using Cronbach’s alpha and intraclass correlation (test–retest). Construct validity was tested using exploratory factor analysis (principal component extraction and equimax orthogonal rotation) and hypothesis testing (Mann–Whitney test). Convergent criterion validity was tested using Spearman’s rho.

Results

The sample comprised 248 patients, 132 women (53.2%), median age (IQR) was 62 years (51–75), 146 patients (58.9%) were 60 years or older, 40% had a low education level. The mean ± SD completion time of the questionnaire was 18.8 ± 9.1 min, and 100% of the items were answered. The questionnaire was self-applied by 46.8% of the sample. The validated Chilean version of the SRI questionnaire showed very good overall reliability (0.95) and by scales (> 0.7). It showed a good correlation with the SF-36, with equivalent scales, a rotated matrix with 8 factors and hypotheses that explain the underlying constructs.

Conclusions

The validated Chilean version of the SRI questionnaire has good psychometric properties. It is feasible, valid, and reliable for application to evaluate patients with CRF in LTH-NIV. It was found to be sensitive to assess the characteristics of the local population.
Estrogen alleviates post-traumatic osteoarthritis progression and decreases p-EGFR levels in female mouse cartilage
Authors: Lu Zhihua , Zhang Aihua , Wang Jingcheng , Han Kuijing , Gao Han
Published: July 2022

Objective

To investigate the effect of estrogen on the progression of post-traumatic osteoarthritis (PTOA) in mice and its possible mechanism.

Methods

Twelve-week-old ICR mice were divided into Group A (female control group), group B (ovariectomized(OVX) group), group C (OVX group supplemented with estrogen), and group D (male group) by destabilization of the medial meniscus (DMM)or sham operation. Safranin O staining was performed at 8 weeks and 12 weeks after operation, and the degree of articular cartilage lesion was evaluated using Mankin score. Twelve weeks after the operation, tissue sections were stained to analyze the matrix metalloproteinase 13(MMP13), phosphorylated epidermal growth factor receptor (p-EGFR) expression and apoptosis of chondrocytes.

Results

Decreased estrogen can significantly increase the weight of mice in female mice. The degree of cartilage damage in the knee joint on the DMM side of female mice was significantly severer than that on the Sham side. The DMM side also showed higher MMP13 expression and increased apoptotic chondrocytes. The degree of cartilage damage in the knee joint on the DMM side of female mice was significantly reduced after estrogen supplementation, and cartilage damage in the knee joint on the DMM side of female mice was less serious than that of male mice. As estrogen levels decreased, the severity of cartilage erosion in the knee joint on the DMM side was aggravated, and p-EGFR expression in the cartilage surface was also higher in female mice contrast to that in male mice. However, minimal changes in p-EGFR expression in the cartilage surface of bilateral knee joints of male mice were observe.

Conclusion

Estrogen has a regulatory effect on PTOA and its inhibits the expression of p-EGFR in cartilage on the knee joint surface and has a protective effect on articular cartilage in female mice.
Costs of multimorbidity: a systematic review and meta-analyses
Authors: Tran Phuong Bich , Kazibwe Joseph , Nikolaidis Georgios F. , Linnosmaa Ismo , Rijken Mieke , van Olmen Josefien
Published: July 2022

Background

Multimorbidity is a rising global phenomenon, placing strains on countries’ population health and finances. This systematic review provides insight into the costs of multimorbidity through addressing the following primary and secondary research questions: What evidence exists on the costs of multimorbidity? How do costs of specific disease combinations vary across countries? How do multimorbidity costs vary across disease combinations? What “cost ingredients” are most commonly included in these multimorbidity studies?

Methods

We conducted a systematic review (PROSPERO: CRD42020204871) of studies published from January 2010 to January 2022, which reported on costs associated with combinations of at least two specified conditions. Systematic string-based searches were conducted in MEDLINE, The Cochrane Library, SCOPUS, Global Health, Web of Science, and Business Source Complete. We explored the association between costs of multimorbidity and country Gross Domestic Product (GDP) per capita using a linear mixed model with random intercept. Annual mean direct medical costs per capita were pooled in fixed-effects meta-analyses for each of the frequently reported dyads. Costs are reported in 2021 International Dollars (I$).

Results

Fifty-nine studies were included in the review, the majority of which were from high-income countries, particularly the United States. (1) Reported annual costs of multimorbidity per person ranged from I$800 to I$150,000, depending on disease combination, country, cost ingredients, and other study characteristics. (2) Our results further demonstrated that increased country GDP per capita was associated with higher costs of multimorbidity. (3) Meta-analyses of 15 studies showed that on average, dyads which featured Hypertension were among the least expensive to manage, with the most expensive dyads being Respiratory and Mental Health condition (I$36,840), Diabetes and Heart/vascular condition (I$37,090), and Cancer and Mental Health condition in the first year after cancer diagnosis (I$85,820). (4) Most studies reported only direct medical costs, such as costs of hospitalization, outpatient care, emergency care, and drugs.

Conclusions

Multimorbidity imposes a large economic burden on both the health system and society, most notably for patients with cancer and mental health condition in the first year after cancer diagnosis. Whether the cost of a disease combination is more or less than the additive costs of the component diseases needs to be further explored. Multimorbidity costing studies typically consider only a limited number of disease combinations, and few have been conducted in low- and middle-income countries and Europe. Rigorous and standardized methods of data collection and costing for multimorbidity should be developed to provide more comprehensive and comparable evidence for the costs of multimorbidity.
Effects of ATLAS 2030 gait exoskeleton on strength and range of motion in children with spinal muscular atrophy II: a case series
Authors: Cumplido-Trasmonte C. , Ramos-Rojas J. , Delgado-Castillejo E. , Garcés-Castellote E. , Puyuelo-Quintana G. , Destarac-Eguizabal M. A. , Barquín-Santos E. , Plaza-Flores A. , Hernández-Melero M. , Gutiérrez-Ayala A. , Martínez-Moreno M. , García-Armada E.
Published: July 2022

Background

Children with spinal muscular atrophy (SMA) present muscle weakness and atrophy that results in a number of complications affecting their mobility, hindering their independence and the development of activities of daily living. Walking has well-recognized physiological and functional benefits. The ATLAS 2030 exoskeleton is a paediatric device that allows gait rehabilitation in children with either neurological or neuromuscular pathologies with gait disorders. The purpose is to assess the effects in range of motion (ROM) and maximal isometric strength in hips, knees and ankles of children with SMA type II after the use of ATLAS 2030 exoskeleton.

Methods

Three children (mean age 5.7 ± 0.6) received nine sessions bi-weekly of 60 min with ATLAS 2030. ROM was assessed by goniometry and strength by hand-held dynamometer. All modes of use of the exoskeleton were tested: stand up and sit down, forward and backward walking, and gait in automatic and active-assisted modes. In addition, different activities were performed during the gait session. A descriptive analysis of all variables was carried out.

Results

The average time of use was 53.5 ± 12.0 min in all sessions, and all participants were able to carry out all the proposed activities as well as to complete the study. Regarding isometric strength, all the measurements increased compared to the initial state, obtaining the greatest improvements for the hip flexors (60.2%) and extensors muscles (48.0%). The ROM increased 12.6% in hip and 34.1% in the ankle after the study, while knee ROM remained stable after the study.

Conclusion

Improvements were showed in ROM and maximal isometric strength in hips, knees and ankles after using ATLAS 2030 paediatric gait exoskeleton in all three children. This research could serve as a preliminary support for future clinical integration of ATLAS 2030 as a part of a long-term rehabilitation of children with SMA.

Trial registration: The approval was obtained (reference 47/370329.9/19) by Comunidad de Madrid Regional Research Ethics Committee with Medical Products and the clinical trial has been registered on Clinical Trials.gov: NCT04837157.
Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models
Authors: Antonello Giulia , Marucco Arianna , Gazzano Elena , Kainourgios Panagiotis , Ravagli Costanza , Gonzalez-Paredes Ana , Sprio Simone , Padín-González Esperanza , Soliman Mahmoud G. , Beal David , Barbero Francesco , Gasco Paolo , Baldi Giovanni , Carriere Marie , Monopoli Marco P. , Charitidis Costas A. , Bergamaschi Enrico , Fenoglio Ivana , Riganti Chiara
Published: July 2022

Background

The widespread use of nano-biomaterials (NBMs) has increased the chance of human exposure. Although ingestion is one of the major routes of exposure to NBMs, it is not thoroughly studied to date. NBMs are expected to be dramatically modified following the transit into the oral-gastric-intestinal (OGI) tract. How these transformations affect their interaction with intestinal cells is still poorly understood. NBMs of different chemical nature—lipid-surfactant nanoparticles (LSNPs), carbon nanoparticles (CNPs), surface modified Fe3O4nanoparticles (FNPs) and hydroxyapatite nanoparticles (HNPs)—were treated in a simulated human digestive system (SHDS) and then characterised. The biological effects of SHDS-treated and untreated NBMs were evaluated on primary (HCoEpiC) and immortalised (Caco-2, HCT116) epithelial intestinal cells and on an intestinal barrier model.

Results

The application of the in vitro SDHS modified the biocompatibility of NBMs on gastrointestinal cells. The differences between SHDS-treated and untreated NBMs could be attributed to the irreversible modification of the NBMs in the SHDS. Aggregation was detected for all NBMs regardless of their chemical nature, while pH- or enzyme-mediated partial degradation was detected for hydroxyapatite or polymer-coated iron oxide nanoparticles and lipid nanoparticles, respectively. The formation of a bio-corona, which contains proteases, was also demonstrated on all the analysed NBMs. In viability assays, undifferentiated primary cells were more sensitive than immortalised cells to digested NBMs, but neither pristine nor treated NBMs affected the intestinal barrier viability and permeability. SHDS-treated NBMs up-regulated the tight junction genes (claudin 3 and 5, occludin, zonula occludens 1) in intestinal barrier, with different patterns between each NBM, and increase the expression of both pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-22, IL-10). Notably, none of these NBMs showed any significant genotoxic effect.

Conclusions

Overall, the results add a piece of evidence on the importance of applying validated in vitro SHDS models for the assessment of NBM intestinal toxicity/biocompatibility. We propose the association of chemical and microscopic characterization, SHDS and in vitro tests on both immortalised and primary cells as a robust screening pipeline useful to monitor the changes in the physico-chemical properties of ingested NBMs and their effects on intestinal cells.
Genetic etiology and clinical challenges of phenylketonuria
Authors: Elhawary Nasser A. , AlJahdali Imad A. , Abumansour Iman S. , Elhawary Ezzeldin N. , Gaboon Nagwa , Dandini Mohammed , Madkhali Abdulelah , Alosaimi Wafaa , Alzahrani Abdulmajeed , Aljohani Fawzia , Melibary Ehab M. , Kensara Osama A.
Published: July 2022

This review discusses the epidemiology, pathophysiology, genetic etiology, and management of phenylketonuria (PKU). PKU, an autosomal recessive disease, is an inborn error of phenylalanine (Phe) metabolism caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene. The prevalence of PKU varies widely among ethnicities and geographic regions, affecting approximately 1 in 24,000 individuals worldwide. Deficiency in the PAH enzyme or, in rare cases, the cofactor tetrahydrobiopterin results in high blood Phe concentrations, causing brain dysfunction. Untreated PKU, also known as PAH deficiency, results in severe and irreversible intellectual disability, epilepsy, behavioral disorders, and clinical features such as acquired microcephaly, seizures, psychological signs, and generalized hypopigmentation of skin (including hair and eyes). Severe phenotypes are classic PKU, and less severe forms of PAH deficiency are moderate PKU, mild PKU, mild hyperphenylalaninaemia (HPA), or benign HPA. Early diagnosis and intervention must start shortly after birth to prevent major cognitive and neurological effects. Dietary treatment, including natural protein restriction and Phe-free supplements, must be used to maintain blood Phe concentrations of 120–360 μmol/L throughout the life span. Additional treatments include the casein glycomacropeptide (GMP), which contains very limited aromatic amino acids and may improve immunological function, and large neutral amino acid (LNAA) supplementation to prevent plasma Phe transport into the brain. The synthetic BH4 analog, sapropterin hydrochloride (i.e., Kuvan®, BioMarin), is another potential treatment that activates residual PAH, thus decreasing Phe concentrations in the blood of PKU patients. Moreover, daily subcutaneous injection of pegylated Phe ammonia-lyase (i.e., pegvaliase; PALYNZIQ®, BioMarin) has promised gene therapy in recent clinical trials, and mRNA approaches are also being studied.
Acute intestinal necrosis due to multiple thrombosis in COVID-19 patient. Report of a case
Authors: Morioka Hirotsugu , Goto Michitoshi , Tanaka Haruka , Momose Hirotaka , Fujino Kazuyoshi , Hagiwara Toshiaki , Aoki Jun , Orihata Michihiro , Kaneko Kotaro
Published: July 2022

Background

While thrombosis is a well-known complication of coronavirus disease 2019 (COVID-19) infection, reports on intestinal necrosis due to intestinal ischemia caused by thrombosis are extremely rare. We herein report a case of intestinal necrosis due to multiple thrombosis in a COVID-19 patient.

Case presentation

The patient was a 64-year-old man. He was admitted to hospital after being diagnosed with COVID-19, the severity was classified as moderate II. Nasal High Flow™ management was conducted along with treatment with tocilizumab, remdesivir, and dexamethasone. Heparin was also administered due to high D-dimer values. As abdominal pain appeared from the 6th day of hospitalization, contrast-enhanced CT was performed, which confirmed multiple thrombosis in the aorta. However, no obvious intestinal ischemia was found. On the 10th day of hospitalization, the patient’s abdominal pain was exacerbated. Upon re-evaluation by CT, he was diagnosed with perforative peritonitis due to ileal ischemic necrosis and emergency surgery was performed. Intraoperative examination revealed perforation due to necrosis at multiple sites in the ileum; thus, partial ileectomy was carried out. Pathological findings also revealed discontinuous multiple intestinal necrosis due to the frequent occurrence of thrombosis. Following surgery, the patient recuperated and was discharged after ventilator management and multimodal therapy at the ICU.

Conclusions

Thrombosis due to COVID-19 complications is rare in the intestinal tract, but also occur. Its initial symptoms might not be captured by CT images, therefore caution is required.