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AnteayerPLOS ONE Medicine&Health

Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in the Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD): Trial protocol and rationale of an open-label pragmatic, prospective randomized controlled

by Sonal Singh, Noelle M. Cocoros, Xiaojuan Li, Kathleen M. Mazor, Mary T. Antonelli, Lauren Parlett, Mark Paullin, Thomas P. Harkins, Yunping Zhou, Paula A. Rochon, Richard Platt, Inna Dashevsky, Carly Massino, Cassandra Saphirak, Sybil L. Crawford, Jerry H. Gurwitz

Context

Potentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, “light touch”, approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.

Objectives

The objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.

Methods

The D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.

Conclusion

This large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia.ClinicalTrials.gov Identifier: NCT05147428.

Prescription drug coverage and effective coverage of three chronic conditions of high prevalence in Chile: Hypertension, diabetes and dyslipidemia

by Isabel Matute, Carla Castillo-Laborde

Background

Access to medicines is a serious problem globally and in Chile. Despite the creation of coverage policies, part of the population with chronic conditions of high prevalence, still does not have access to the medicines it requires and disease control continues to be low. The objective of the study was to estimate the medication use and effective coverage for diabetes, dyslipidemia and hypertension in Chile, analyzing them according to sociodemographic variables and social determinants of health.

Methods

Cross-sectional analytical study with information from the 2016–2017 National Health Survey (sample = 6,233 people aged 15 years or older, expanded = 14,518,969). Descriptive analyses of medication use and effective coverage for hypertension, diabetes and dyslipidemia were carried out, and multivariate logistic regression models were developed to analyze possible associations with variables of interest.

Results

60% of people with hypertension or diabetes use medications and only 27.7% in dyslipidemia. While 54.2% of those with diabetes have their glycemia controlled, in hypertension and dyslipidemia the effective coverage drops to 33.3% and 6.6%, respectively. There are no differences in use by health system, but there are differences in the control of hypertension and diabetes, favoring beneficiaries of the private subsystem. Effective coverage of dyslipidemia and hypertension also increases in those using medications. The drugs coincide with the established protocols, although beneficiaries of the private sector report greater use of innovative drugs.

Conclusion

A significant proportion of Chileans with hypertension, diabetes or dyslipidemia still do not use the required medications and do not control their conditions.

The incredible shrinking puffin: Decreasing size and increasing proportional bill size of Atlantic puffins nesting at Machias Seal Island

by Heather L. Major, Joy E. Rivers, Quinn B. Carvey, Antony W. Diamond

Climate change imposes physiological constraints on organisms particularly through changing thermoregulatory requirements. Bergmann’s and Allen’s rules suggest that body size and the size of thermoregulatory structures differ between warm and cold locations, where body size decreases with temperature and thermoregulatory structures increase. However, phenotypic plastic responses to malnutrition during development can result in the same patterns while lacking fitness benefits. The Gulf of Maine (GOM), located at the southern end of the Labrador current, is warming faster than most of the world’s oceans, and many of the marine species that occupy these waters exist at the southern edge of their distributions including Atlantic puffins (Fratercula arctica; hereafter “puffin”). Monitoring of puffins in the GOM, at Machias Seal Island (MSI), has continued annually since 1995. We asked whether changes in adult puffin body size and the proportional size of bill to body have changed with observed rapid ocean warming. We found that the size of fledgling puffins is negatively related to sea surface temperature anomalies (warm conditions = small fledgers), adult puffin size is related to fledgling size (small fledgers = small adults), and adult puffins have decreased in size in recent years in response to malnutrition during development. We found an increase in the proportional size of bill to wing chord, likely in response to some mix of malnutrition during development and increasing air temperatures. Although studies have assessed clinal variation in seabird morphology with temperature, this is the first study addressing changes in seabird morphology in relation to ocean warming. Our results suggest that puffins nesting in the GOM have morphological plasticity that may help them acclimate to ocean warming.

Psychometric properties of the Fluoride Hesitancy Identification Tool (FHIT)

by Adam C. Carle, Isabella Pallotto, Todd C. Edwards, Richard Carpiano, Darragh C. Kerr, Donald L. Chi

Introduction

Some caregivers are hesitant about topical fluoride for their children despite evidence that fluoride prevents caries and is safe. Recent work described a five domain model of caregivers’ topical fluoride hesitancy. We developed the Fluoride Hesitancy Identification Tool (FHIT) item pool based on the model. This study sought to evaluate the FHIT’s psychometric properties in an effort to generate a short, simple to score, reliable, and valid tool that measures caregivers’ topical fluoride hesitancy.

Methods

In 2021 and 2022, we conducted an observational, cross-sectional study of caregivers, collecting data from two independent caregiver samples (n1 = 523; n2 = 612). The FHIT item pool included 33 items. We used confirmatory factor analyses (CFA) to examine whether the FHIT items measured five separate domains as hypothesized and to reduce the number of items. We then fit item response theory (IRT) models and computed Cronbach’s alpha for each domain. Last, we examined the construct validity of the FHIT and evaluated scoring approaches.

Results

After dropping 8 items, CFA supported a five factor model of topical fluoride hesitancy, with no cross-loadings (RMSEA = 0.079; SRMR = 0.057; CFI = 0.98; TLI = 0.98). We further reduced the items to four per domain (20 items total). Marginal alphas showed that the item sets provided reliability of ≥0.90 at hesitancy levels at and above average. The domains correlated more strongly with each other and topical fluoride refusal than with other questions on the survey.

Discussion

Our results support the FHIT’s ability to reliably and validly measure five domains of topical fluoride hesitancy using the average score of the four items in each domain.

Educational technologies for teaching hand hygiene: Systematic review

by Daiane Rubinato Fernandes, Bruna Nogueira dos Santos, Carolina Scoqui Guimarães, Elaine Barros Ferreira, Amanda Salles Margatho, Paula Elaine Diniz dos Reis, Didier Pittet, Renata Cristina de Campos Pereira Silveira

Aim

To gather available scientific evidence on technologies used to teach hand hygiene to professional populations and lays involved in health care in the hospital setting. This systematic review was designed as proposed by Preferred Reporting Items for Systematic Reviews and Meta-Analysis, included studies reporting primary, original, quantitative research findings with no date limit and written in English, Spanish or Portuguese. The search was performed in the following electronic databases: Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica dataBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde, US National Library of Medicine, Scopus, Web of Science, Google Scholar and ProQuest. The eligibility criteria were applied independently by two reviewers to select the studies, first by reading the titles and abstracts on the Rayyan platform and then by full text reading of the eligible studies. After a descriptive analysis, the studies were subjected to critical evaluation of their methodological quality using JBI tools.

Results

Seven studies were included, addressing various methods for teaching hand hygiene using different technological resources, such as audiovisual electronic devices, videos, virtual reality, and gamification using tablets and smartphones, in different populations.

Conclusion

Using technologies to teach hand hygiene considerably helps patients, visitors, and relatives in learning the procedures and efficiently improves hand hygiene compliance rates among healthcare professionals, creating evidence-based repetitive learning opportunities for patients and caregivers.

Proteomic and transcriptomic characterisation of FIA10, a novel murine leukemic cell line that metastasizes into the brain

by Ursula Just, Helmut Burtscher, Sylvia Jeratsch, Meike Fischer, Carol Stocking, Jens Preussner, Mario Looso, Ralf Schwanbeck, Stefan Günther, Ralf Huss, Lynne Mullen, Thomas Braun

Brain metastasis leads to increased mortality and is a major site of relapse for several cancers, yet the molecular mechanisms of brain metastasis are not well understood. In this study, we established and characterized a new leukemic cell line, FIA10, that metastasizes into the central nervous system (CNS) following injection into the tail vein of syngeneic mice. Mice injected with FIA10 cells developed neurological symptoms such as loss of balance, tremor, ataxic gait and seizures, leading to death within 3 months. Histopathology coupled with PCR analysis clearly showed infiltration of leukemic FIA10 cells into the brain parenchyma of diseased mice, with little involvement of bone marrow, peripheral blood and other organs. To define pathways that contribute to CNS metastasis, global transcriptome and proteome analysis was performed on FIA10 cells and compared with that of the parental stem cell line FDCP-Mix and the related FIA18 cells, which give rise to myeloid leukemia without CNS involvement. 188 expressed genes (RNA level) and 189 proteins were upregulated (log2 ratio FIA10/FIA18 ≥ 1) and 120 mRNAs and 177 proteins were downregulated (log2 ratio FIA10/FIA18 ≤ 1) in FIA10 cells compared with FIA18 cells. Major upregulated pathways in FIA10 cells revealed by biofunctional analyses involved immune response components, adhesion molecules and enzymes implicated in extracellular matrix remodeling, opening and crossing the blood-brain barrier (BBB), molecules supporting migration within the brain parenchyma, alterations in metabolism necessary for growth within the brain microenvironment, and regulators for these functions. Downregulated RNA and protein included several tumor suppressors and DNA repair enzymes. In line with the function of FIA10 cells to specifically infiltrate the brain, FIA10 cells have acquired a phenotype that permits crossing the BBB and adapting to the brain microenvironment thereby escaping immune surveillance. These data and our model system FIA10 will be valuable resources to study the occurrence of brain metastases and may help in the development of potential therapies against brain invasion.

Towards system redesign: An exploratory analysis of neurodivergent traits in a childhood population referred for autism assessment

by Jason Lang, Georgia Wylie, Caroline Haig, Christopher Gillberg, Helen Minnis

Background

Children’s health services in many countries are moving from single condition diagnostic silo assessments to considering neurodevelopment in a more holistic sense. There has been increasing recognition of the importance of clinical overlap and co-occurrence of different neurotypes when assessing neurodivergent children. Using a cross-sectional service evaluation design, we investigated the overlap of neurodivergences in a cohort of children referred for autism assessment, focusing on motor, learning, and attention/activity level domains. We aimed to determine what proportion of children in a cohort referred for an autism assessment showed traits of additional neurodivergences, and what proportion were further investigated.

Methods

We evaluated anonymised medical records of children aged between two and 17 years referred for autism assessment. We used validated questionnaires to assess for neurodivergent traits. A weighted scoring system was developed to determine traits in each neurodevelopmental domain and a score above the median was considered to indicate a neurodivergent trait. Evidence of further investigations were recorded. We then examined the relationships between autism traits and traits of additional neurodivergence.

Results

114 participants were included for evaluation. 62.3% (n = 71) had completed questionnaires for analysis. Of these, 71.8% (n = 51) scored greater than the median for at least one additional neurotype, indicating the presence of other neurodivergent traits, and 88.7% (n = 64) attracted a diagnosis of autism. Only 26.3% of children with evidence of additional neurotypes were further investigated beyond their autism assessment.

Conclusions

Our results demonstrate the extensive overlap between additional neurodivergent traits in a population of children referred with suspected autism and show that only a small proportion were further investigated. The use of standardised questionnaires to uncover additional neurodivergences may have utility in improving the holistic nature of neurodevelopmental assessments.

Efficacy of early cardiac rehabilitation after acute myocardial infarction: Randomized clinical trial protocol

by Caroline Schon, Amanda Felismino, Joceline de Sá, Renata Corte, Tatiana Ribeiro, Selma Bruno

The acute myocardial infarction (AMI) present high mortality rate that may be reduced with cardiac rehabilitation. Despite its good establishment in outpatient care, few studies analyzed cardiac rehabilitation during hospitalization. Thus, this study aims to clarify the safety and efficacy of early cardiac rehabilitation after AMI. This will be a clinical, controlled, randomized trial with blind outcome evaluation and a superiority hypothesis. Twenty-four patients with AMI will be divided into two groups (1:1 allocation ratio). The intervention group will receive an individualized exercise-based cardiac rehabilitation protocol during hospitalization and a semi-supervised protocol after hospital discharge; the control group will receive conventional care. The primary outcomes will be the cardiac remodeling assessed by cardiac magnetic resonance imaging, functional capacity assessed by maximal oxygen consumption, and cardiac autonomic balance examined via heart rate variability. Secondary outcomes will include safety and the total exercise dose provided during the protocol. Statistical analysis will consider the intent-to-treat analysis. Trial registration. Trial registration number: Brazilian Registry of Clinical Trials (ReBEC) (RBR- 9nyx8hb).

Regional variation and temporal trends in transcatheter and surgical aortic valve replacement in Switzerland: A population-based small area analysis

by Carla Schenker, Maria M. Wertli, Lorenz Räber, Alan G. Haynes, Arnaud Chiolero, Nicolas Rodondi, Radoslaw Panczak, Drahomir Aujesky

Background

Aortic valve stenosis (AS) is the most common valvular heart disease and if severe, is treated with either transcatheter (TAVR) or surgical aortic valve replacement (SAVR). We assessed temporal trends and regional variation of these interventions in Switzerland and examined potential determinants of geographic variation.

Methods

We conducted a population-based analysis using patient discharge data from all Swiss public and private acute care hospitals from 2013 to 2018. We generated hospital service areas (HSAs) based on patient flows for TAVR. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). Using multilevel regression, we calculated the influence of calendar year and regional demographics, socioeconomic factors (language, insurance status), burden of disease, and number of cardiologists/cardiovascular surgeons on geographic variation.

Results

Overall, 8074 TAVR and 11,825 SAVR procedures were performed in 8 HSAs from 2013 to 2018. Whereas the age-/sex-standardized rate of TAVR increased from 12 to 22 procedures/100,000 persons, the SAVR rate decreased from 33 to 24 procedures during this period. After full adjustment, the predicted TAVR and SAVR rates varied from 12 to 22 and 20 to 35 per 100,000 persons across HSAs, respectively. The regional procedure variation was low to moderate over time, with a low overall variation in TAVR (EQ 1.9, SCV 3.9) and SAVR (EQ 1.6, SCV 2.2). In multilevel regression, TAVR rates increased annually by 10% and SAVR rates decreased by 5%. Determinants of higher TAVR rates were older age, male sex, living in a German speaking area, and higher burden of disease. A higher proportion of (semi)private insurance was also associated with higher TAVR and lower SAVR rates. After full adjustment, 10.6% of the variance in TAVR and 18.4% of the variance in SAVR remained unexplained. Most variance in TAVR and SAVR rates was explained by language region and insurance status.

Conclusion

The geographic variation in TAVR and SAVR rates was low to moderate across Swiss regions and largely explained by differences in regional demographics and socioeconomic factors. The use of TAVR increased at the expense of SAVR over time.

Screening for antibacterial and cytotoxic activities of Sri Lankan marine sponges through microfractionation: Isolation of bromopyrrole alkaloids from <i>Stylissa massa</i>

by Lakmini Kosgahakumbura, Jayani Gamage, Luke P. Robertson, Taj Muhammad, Björn Hellman, Ulf Göransson, Prabath Jayasinghe, Chamari Hettiarachchi, Paco Cárdenas, Sunithi Gunasekera

Sri Lanka is a biodiversity hotspot and one of the richest geographical locations of marine sponges in the Indian ocean. However, the most extensive taxonomical study on Sri Lankan sponge biodiversity dates back ~100 years and only a limited number of studies have been conducted on sponge natural products. In the current study, 35 marine sponge specimens (collected from 16 sponge habitats around Sri Lanka) were identified, microfractionated and evaluated for antibacterial and anticancer assays. In total, 30 species were characterized, of which 19 species gave extracts with antibacterial and/or cytotoxic activities. Microfractionated organic extract of Aciculites orientalis gave the most potent antibacterial activity against Staphylococcus aureus and strongest lymphoma cell toxicity was exhibited by the organic extract of Acanthella sp. Guided by the molecular ion peaks in the bioactive fractions, large-scale extraction of Stylissa massa led to the isolation of three bromopyrrole alkaloids, sceptrin, hymenin and manzacidin A/C. Of these, sceptrin exhibited broad spectrum antibacterial activity against both Escherichia coli and S. aureus (MIC of 62.5 μM against both species). Based on natural product literature, seven promising species were identified as understudied. Their further exploration may lead to the discovery of structurally novel compounds.

Quantitative changes in the corneal endothelium and central corneal thickness during anterior chamber inflammation: A systematic review and meta-analysis

by Germán Mejía-Salgado, Paula Tatiana Muñoz-Vargas, Carlos Cifuentes-González, Gabriela Flórez-Esparza, Rebeca Paquentín-Jiménez, Miguel Ángel Castro-Monreal, Naomi Medina-Galindo, Gilma Norella Hernández-Herrera, Luz Elena Concha-del-Río, Alejandra de-la-Torre

Purpose

To establish the effects of anterior chamber inflammation (ACI) on the corneal endothelium parameters and central corneal thickness (CCT).

Methods

We conducted a comprehensive literature review using medical databases (PubMed, EMBASE, VHL, and medRxiv) on March 8, 2023, for studies that included patients with ACI who had undergone specular microscopy or pachymetry. Case series with >10 patients, cross-sectional, case-control, and cohort studies were included. The risk of bias was assessed using CLARITY tools and validated scales such as those by Hassan Murad et al. and Hoy et al. A narrative synthesis and a quantitative standardized mean difference meta-analysis, I2 heterogeneity assessment, and publication bias tests were conducted. The study was registered in PROSPERO (CRD42023420148) and approved by the Universidad del Rosario ethical committee (DVO005 2277- CV1712).

Results

Thirty-four studies, encompassing 1,388 eyes with ACI, were included. Compared with healthy controls, overall, ACI eyes show significant mean differences in endothelial parameters (endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX)) (P Conclusion

ACI leads to significant alterations in endothelial parameters and CCT. The primary contributors to these changes are increased IOP, uveitis duration, and intraocular surgeries. Further studies are needed to explore the impact of ACI etiology on the endothelium, potential biases in IOP measurements during acute ACI episodes, and the potential necessity for monitoring the endothelial parameters and CCT in patients with chronic ACI.

Molecular effects of polystyrene nanoplastics on human neural stem cells

by Raquel Martin-Folgar, Mª Carmen González-Caballero, Mónica Torres-Ruiz, Ana I. Cañas-Portilla, Mercedes de Alba González, Isabel Liste, Mónica Morales

Nanoplastics (NPs) have been found in many ecological environments (aquatic, terrestrial, air). Currently, there is great concern about the exposition and impact on animal health, including humans, because of the effects of ingestion and accumulation of these nanomaterials (NMs) in aquatic organisms and their incorporation into the food chain. NPs´ mechanisms of action on humans are currently unknown. In this study, we evaluated the altered molecular mechanisms on human neural stem cell line (hNS1) after 4 days of exposure to 30 nm polystyrene (PS) NPs (0.5, 2.5 and 10 μg/mL). Our results showed that NPs can induce oxidative stress, cellular stress, DNA damage, alterations in inflammatory response, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases.

Bridging the gap: A new species of arboreal <i>Abronia</i> (Squamata: Anguidae) from the Northern Highlands of Chiapas, Mexico

by Adam G. Clause, Roberto Luna-Reyes, Oscar M. Mendoza-Velázquez, Adrián Nieto-Montes de Oca, Israel Solano-Zavaleta

The mountain forests of Middle America are renowned for their endemic biodiversity, and arboreal alligator lizards (genus Abronia) are high-profile vertebrates endemic to this region. In this work, we describe a new species of arboreal Abronia that is known only from the type locality in the Northern Highlands of Chiapas, Mexico. The new species is diagnosed from all other members of the genus Abronia by the following combination of characters: lack of protuberant or spine-like supra-auricular scales, lack of protuberant or casque-like posterolateral head scales, dorsum of head pale yellow with distinct dark markings, 35–39 transverse dorsal scale rows, lateralmost row of ventral scales enlarged relative to adjacent medial row, and dorsum brown with darker crossbands that are sometimes reduced to rows of spots. We provisionally include the new species in the subgenus Lissabronia based on genomic and morphological evidence, but our results also suggest a close relationship to the subgenus Abaculabronia. The new species is geographically separated from the nearest Lissabronia and Abaculabronia species by the lowland Central Depression of Chiapas. Ongoing habitat loss and other factors imperil the new species, leading us to propose its listing under multiple threatened species frameworks. Because the Northern Highlands have poor coverage of protected areas, we briefly comment on the potential of this new species for stimulating conservation in the region.

Physical activity among older adults with multimorbidity: Evidence from a population-based health survey

by Bruno Holanda Ferreira, Ricardo Goes de Aguiar, Edige Felipe de Sousa Santos, Chester Luiz Galvão Cesar, Moisés Goldbaum, Camila Nascimento Monteiro

Introduction

The promotion of physical activity has been recognized as an important component in the management and prevention of multimorbidity, a condition that is increasing prevalent worldwide, including in Brazil. However, there is a scarcity of studies exploring the disparity in physical activity levels between individuals with and without multimorbidity. Therefore, the study aimed to estimate the prevalence of multimorbidity and physical activity among older adults, as well as analyze the relationship of a sufficient level of physical activity and multimorbidity, while considering sociodemographic characteristics of residents in São Paulo, Brazil.

Materials and methods

Data from 1.019 participants aged 60 years or older (59.7% female; mean age 69.7±7.7) were collected from the Health Survey (ISA-Capital, 2015) conducted in the city of São Paulo, Brazil. We defined multimorbidity as the presence of two or more chronic conditions, and for physical activity, classified a sufficient level (≥150 min/week). Prevalence Ratios (PR) with 95% Confidence Intervals (95%CI) were estimated using univariate and multivariate Poisson regression to examine the relationship between multimorbidity and sufficient level of physical activity.

Results

67.7% of the participants lived with multimorbidity, while 30.1% had achieved a sufficient level of physical activity. There was a higher prevalence of sufficient level of physical activity among older adults with two (PR = 1.38; 95%CI 1.02–1.88) and four (PR = 1.37; 95%CI 1.00–1.87) chronic conditions. Older adults with multimorbidity who were 70 years or older (PR = 1.77; 95%IC 1.13–2.77), female (PR = 1.65; 95%CI 1.16–2.36), without a partner (PR = 1.43; 95%IC 1.03–1.99), and had a per capita income of 1 to 2.5 (PR = 1.83; 95%IC 1.00–3.33) were more likely to achieve a sufficient level of physical activity compared to their peers without multimorbidity.

Conclusions

The study highlights sociodemographic disparities in the sufficient level of physical activity among multimorbidity, suggesting the importance of considering these factors when planning public policies aimed at promoting physical activity.

Gait analysis: An effective tool to mechanically monitor the bone regeneration of critical-sized defects in tissue engineering applications

by Pablo Blázquez-Carmona, Juan Mora-Macías, Juan Morgaz, María del Mar Granados, Jaime Domínguez, Esther Reina-Romo

Introduction

Tissue engineering has emerged as an innovative approach to treat critical-size bone defects using biocompatible scaffolds, thus avoiding complex distraction surgeries or limited stock grafts. Continuous regeneration monitoring is essential in critical-size cases due to the frequent appearance of non-unions. This work evaluates the potential clinical use of gait analysis for the mechanical assessment of a tissue engineering regeneration as an alternative to the traditional and hardly conclusive manual or radiological follow-up.

Materials and methods

The 15-mm metatarsal fragment of eight female merino sheep was surgically replaced by a bioceramic scaffold stabilized with an external fixator. Gait tests were performed weekly by making the sheep walk on an instrumented gangway. The evolution of different kinematic and dynamic parameters was analyzed for all the animal’s limbs, as well as asymmetries between limbs. Finally, potential correlation in the recovery of the gait parameters was evaluated through the linear regression models.

Results

After surgery, the operated limb has an altered way of carrying body weight while walking. Its loading capacity was significantly reduced as the stance phases were shorter and less impulsive. The non-operated limbs compensated for this mobility deficit. All parameters were normalizing during the consolidation phase while the bone callus was simultaneously mineralizing. The results also showed high levels of asymmetry between the operated limb and its contralateral, which exceeded 150% when analyzing the impulse after surgery. Gait recovery significantly correlated between symmetrical limbs.

Conclusions

Gait analysis was presented as an effective, low-cost tool capable of mechanically predicting the regeneration of critical-size defects treated by tissue engineering, as comparing regeneration processes or novel scaffolds. Despite the progressive normalization as the callus mineralized, the bearing capacity reduction and the asymmetry of the operated limb were more significant than in other orthopedic alternatives.

Screening for the risk of canine impaction, what are the presumptive signs and how does it affect orthodontics? A cross-sectional study in France

by Damien Brézulier, Steeven Carnet, Alexia Marie-Cousin, Jean-Louis Sixou

Purpose

The treatment of impacted canines is a challenge for orthodontists. The availability of suggestive clinical signs has become crucial for treatment before the potential for evolution ceases. The main objective was to evaluate the prevalence of the suspected displaced canine (SDC) and to highlight factors easily identifiable from the oral examination.

Methods

SDC was assessed on panoramic X-rays, on the basis of the angle with the median sagittal plane and the degree of overlap with the permanent lateral incisor. Its association with mesio-distal tooth and palate widths was assessed by univariate analysis. Next, the association of SDC with temporary tooth extraction, expansion and/or premolar extraction was considered using the same modality.

Results

In this retrospective study, the records of 292 patients aged 7 to 13 years were reviewed. SDC was detected in 39% of patients i.e., 28,8% of observed canines. Reduced coronal mesio-distal diameters of permanent maxillary central incisors, 8.7 ± 0.6 mm versus 8.8 ± 0.7 mm (p Conclusion

This study confirmed the interest of panoramic X-rays in detected canines at risk of SDC. Dental factors can be combined to make screening more reliable and predict impaction that makes orthodontics complex.

Trial registration number

Opinion n°21.131, dated 09.21.2021, retrospectively registered.

Long- versus short-duration systemic corticosteroid regimens for acute exacerbations of COPD: A systematic review and meta-analysis of randomized trials and cohort studies

by Zhen Zhao, Owen Lou, Yiyang Wang, Raymond Yin, Carrie Gong, Florence Deng, Ethan C. Wu, Jing Yi Xie, Jerry Wu, Avery Ma, Yongzhi Guo, Wei Ting Xiong

While systemic corticosteroids quicken patient recovery during acute exacerbations of COPD, they also have many adverse effects. The optimal duration of corticosteroid administration remains uncertain. We performed a systematic review and meta-analysis to compare patient outcomes between short- (≤7 days) and long- (>7 days) corticosteroid regimens in adults with acute exacerbations of COPD. MEDLINE, EMBASE, CENTRAL, and hand searches were used to identify eligible studies. Risk of bias was assessed using the Cochrane RoB 2.0 tool and ROBINS-I. Data were summarized as ORs (odds ratios) or MDs (mean differences) whenever possible and qualitatively described otherwise. A total of 11532 participants from eight RCTs and three retrospective cohort studies were included, with 1296 from seven RCTs and two cohort studies eligible for meta-analyses. Heterogeneity was present in the methodology and settings of the studies. The OR (using short duration as the treatment arm) for mortality was 0.76 (95% CI = 0.40–1.44, n = 1055). The MD for hospital length-of-stay was -0.91 days (95% CI = -1.81–-0.02 days, n = 421). The OR for re-exacerbations was 1.31 (95% CI = 0.90–1.90, n = 552). The OR for hyperglycemia was 0.90 (95% CI = 0.60–1.33, n = 423). The OR for infection incidence was 0.96 (95% CI = 0.59–1.156, n = 389). The MD for one-second forced expiratory volume change was -18.40 mL (95% CI = -111.80–75.01 mL, n = 161). The RCTs generally had low or unclear risks of bias, while the cohort studies had serious or moderate risks of bias. Our meta-analyses were affected by imprecision due to insufficient data. Some heterogeneity was present in the results, suggesting population, setting, and treatment details are potential prognostic factors. Our evidence suggests that short-duration treatments are not worse than long-duration treatments in moderate/severe exacerbations and may lead to considerably better outcomes in milder exacerbations. This supports the current GOLD guidelines. Trial registration: Our protocol is registered in PROSPERO: CRD42023374410.

Proposal for a physiotherapy assessment form for the evaluation of women patients with uro-gynecological disorders: A Delphi study

by Ana González-Castro, Raquel Leirós-Rodríguez, Óscar Rodríguez-Nogueira, Mª José Álvarez-Álvarez, Arrate Pinto-Carral, Elena Andrade-Gómez

Background

The correct selection of treatment techniques and methods in physiotherapy depends directly on a well-structured anamnesis, examination and assessment. Within urogynecological and obstetric physiotherapy there is no standardized and protocolized assessment that allows to follow established steps. For all this, the main objective of this study was to identify the assessment items that should be included in the a physiotherapeutic uro-gynecological assessment.

Methods

Delphi study through a group of experts. Prior to this, a systematic search was carried out, accompanied by a review of grey literature, to obtain the possible items to be included in the forms. Subsequently, a Delphi study with two consecutive rounds of questionnaires was developed. A total of 6 expert physiotherapists participated in the study.

Results

The initial questionnaire had 97 items and after two rounds one item was eliminated to obtain a total of 96 items in the final questionnaire.

Conclusions

The experts agreed on most of the choices and finally obtained a standardized and protocolized assessment in uro-gynecological physiotherapy. Furthermore, this proposal should be considered by other professionals involved in the process of evaluation and treatment of pelvi-perineal alterations.

A simple dissection method for the isolation of mouse trabecular meshwork cells

by Maximilian Binter, Fridolin Langer, Xiaonan Hu, Migle Lindziute, Carsten Framme, Jan Tode, Heiko Fuchs

Purpose

The outflow pathway, especially trabecular meshwork (TM), plays an essential role in glaucoma, and the availability of TM cells is crucial for in vitro research. So far, the isolation of TM cells from mice has been anything but manageable due to the small size of the eye. Direct isolation using a stereomicroscope and forceps requires a high grade of dexterity. Indirect isolation is based on the phagocytic properties of TM cells and involves injecting magnetic microspheres into the anterior chamber of live mice followed by isolation. Therefore, a simpler, less expensive, and nonexperimental strategy for isolating mouse TM cells would be desirable.

Methods

After enucleation, the eyes were cut in half anterior-to-posteriorly. The lens and posterior segment were removed. Iris and the attached ciliary body were gently pulled backward and disconnected from the remaining tissue to expose the TM. By incising through the cornea anteriorly and posteriorly of the TM, the cornea/TM stripe could be isolated. The cornea/TM stripe was cultured with the pigmented side down in a 6-well. The outgrowing pigmented cells were analyzed by immunocytochemistry and mRNA expression for previously described TM cell markers. The phagocytic properties of the cells were additionally confirmed using fluorescent microspheres.

Results

Pigmented phagocytic cells were the first to grow out of the cornea/TM strips after approximately 4–7 days. Cells were positive for Collagen IV, Fibronectin1, Vimentin, and Actin alpha 2 and could phagocytize fluorescent microbeads. Cross-linked actin networks were visible after 9 days of exposure to TGFB2 (transforming growth factor-beta 2). Additionally, treatment with 500 nM Dexamethasone for one week increased myocilin expression, as previously reported for TM cells. In addition, we proved that this method can also be used in albino mice, which lack pigmentation of the trabecular meshwork.

Conclusions

The isolated cells show phagocytic properties and specific expression of markers reported in TM cells. Therefore, our dissection-based method is inexpensive and reproducible for isolating TM cells in mice.

The immune response of the whitefly <i>Trialeurodes vaporariorum</i> (Hemiptera: Aleyrodidae) when parasitized by <i>Eretmocerus eremicus</i> (Hymenoptera: Aphelinidae)

by Jorge Contreras-Garduño, Pedro Torres-Enciso, Ricardo Ramirez-Romero

In insects, the innate immune system is subdivided into cellular and humoral defenses. When parasitoids attack insects, both reactions can be activated and notably, the phenoloxidase (PO) cascade and lytic activity are part of both cellular and humoral defenses. However, to our knowledge, no study has characterized any immune response of the whitefly Trialeurodes vaporariorum (Hemiptera: Aleyrodidae) to the attack of Eretmocerus eremicus (Hymenoptera: Aphelinidae). Therefore, the first objective of the present study was to determine whether whitefly nymphs recently parasitized by E. eremicus exhibit any immune response. For this, we estimate the level of prophenoloxidase (proPO), phenoloxidase (PO), and lytic activity by colorimetric assays. A second objective was to assess whether the observed whitefly immune response could be related to a previously reported preference of the predator Geocoris punctipes (Hemiptera: Lygaeidae) for non-parasitized nymphs. We therefore offered non-parasitized and recently parasitized nymphs to the predator. Our results show that parasitism of whitefly nymphs by E. eremicus induced a highly estimated level of proPO and PO, and a lower level of lytic activity. In addition, we found that G. punctipes did not show a preference for non-parasitized over recently parasitized nymphs. The nymphs of T. vaporariorum activated the PO pathway against E. eremicus; however, the increase in proPO and PO levels was traded-off with decreased lytic activity. In addition, the previously reported preference for non-parasitized nymphs was not seen in our experiments, indicating that the induced immune response did not affect predator behavior by G. punctipes.
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