Architectonic principles of polyproline II helix bundle protein domains.

Glycine rich polyproline II helix assemblies are an emerging class of natural domains found in several proteins with different functions and diverse origins. The distinct properties of these domains relative to those composed of α-helices and ß-sheets could make glycine-rich polyproline II helix assemblies a useful building block for protein design. Whereas the high population of polyproline II conformers in disordered state ensembles could facilitate glycine-rich polyproline II helix folding, the architectonic bases of these structures are not well known. Here, we compare and analyze their structures to uncover common features. These protein domains are found to be highly tolerant of distinct flanking sequences. This speaks to the robustness of this fold and strongly suggests that glycine rich polyproline II assemblies could be grafted with other protein domains to engineer new structures and functions. These domains are also well packed with few or no cavities. Moreover, a significant trend towards antiparallel helix configuration is observed in all these domains and could provide stabilizing interactions among macrodipoles. Finally, extensive networks of Cα-H···OC hydrogen bonds are detected in these domains. Despite their diverse evolutionary origins and activities, glycine-rich polyproline II helix assemblies share architectonic features which could help design novel proteins.

The influence of scale-dependent geodiversity on species distribution models in a biodiversity hotspot.

Improving models of species' distributions is essential for conservation, especially in light of global change. Species distribution models (SDMs) often rely on mean environmental conditions, yet species distributions are also a function of environmental heterogeneity and filtering acting at multiple spatial scales. Geodiversity, which we define as the variation of abiotic features and processes of Earth's entire geosphere (inclusive of climate), has potential to improve SDMs and conservation assessments, as they capture multiple abiotic dimensions of species niches, however they have not been sufficiently tested in SDMs. We tested a range of geodiversity variables computed at varying scales using climate and elevation data. We compared predictive performance of MaxEnt SDMs generated using CHELSA bioclimatic variables to those also including geodiversity variables for 31 mammalian species in Colombia. Results show the spatial grain of geodiversity variables affects SDM performance. Some variables consistently exhibited an increasing or decreasing trend in variable importance with spatial grain, showing slight scale-dependence and indicating that some geodiversity variables are more relevant at particular scales for some species. Incorporating geodiversity variables into SDMs, and doing so at the appropriate spatial scales, enhances the ability to model species-environment relationships, thereby contributing to the conservation and management of biodiversity. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.

A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases.

Infectious keratitis is a vision-threatening microbial infection. The increasing antimicrobial resistance and the fact that severe cases often evolve into corneal perforation necessitate the development of alternative therapeutics for effective medical management. Genipin, a natural crosslinker, was recently shown to exert antimicrobial effects in an ex vivo model of microbial keratitis, highlighting its potential to serve as a novel treatment for infectious keratitis. This study aimed to evaluate the antimicrobial and anti-inflammatory effects of genipin in an in vivo model of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) keratitis. Clinical scores, confocal microscopy, plate count, and histology were carried out to evaluate the severity of keratitis. To assess the effect of genipin on inflammation, the gene expression of pro- and anti-inflammatory factors, including matrix metalloproteinases (MMPs), were evaluated. Genipin treatment alleviated the severity of bacterial keratitis by reducing bacterial load and repressing neutrophil infiltration. The expression of interleukin 1B (IL1B), interleukin 6 (IL6), interleukin 8 (IL8), interleukin 15 (IL15), tumor necrosis factor-α (TNF-α), and interferon γ (IFNγ), as well as MMP2 and MMP9, were significantly reduced in genipin-treated corneas. Genipin promoted corneal proteolysis and host resistance to S. aureus and P. aeruginosa infection by suppressing inflammatory cell infiltration, regulating inflammatory mediators, and downregulating the expression of MMP2 and MMP9.

The impact of a two-year long COVID-19 public health restriction program on mechanical thrombectomy outcomes in a stroke network.

OBJECTIVE: The purpose of this study was to evaluate the impact of COVID-19 pandemic public health restrictions on our drip and ship mechanical thrombectomy program in Santiago Chile. MATERIALS AND METHODS: This was a retrospective analysis of a prospectively collected database comparing two cohorts, one during a two-year period before COVID-19 and the second during the two years of the pandemic at our metropolitan stroke program. RESULTS: A total of 100 patients were included in the pre COVID-19 cohort (cohort 1) and 121 in the COVID-19 cohort (cohort 2). There was a significant difference between cohorts, with older patients, different occlusion sites and higher door to arterial puncture time during the COVID-19 period. A non-significant trend for worse 90-day outcomes and higher mortality was present in cohort 2. There were no statistical differences in safety treatment parameters. CONCLUSIONS: COVID-19 pandemic has had a measurable impact on our mechanical thrombectomy program. Results showed similarities to other reported Latin American series, where less robust health systems could adapt less efficiently compared to developed countries. After two years of public health restrictions, there were changes in the treatment population characteristics, delay in some internal management metrics and a non-significant trend to worse 90-day outcomes and higher mortality.

Magnetic Torus Microreactor as a Novel Device for Sample Treatment via Solid-Phase Microextraction Coupled to Graphite Furnace Atomic Absorption Spectroscopy: A Route for Arsenic Pre-Concentration.

This work studied the feasibility of using a novel microreactor based on torus geometry to carry out a sample pretreatment before its analysis by graphite furnace atomic absorption. The miniaturized retention of total arsenic was performed on the surface of a magnetic sorbent material consisting of 6 mg of magnetite (Fe3O4) confined in a very small space inside (20.1 µL) a polyacrylate device filling an internal lumen (inside space). Using this geometric design, a simulation theoretical study demonstrated a notable improvement in the analyte adsorption process on the solid extractant surface. Compared to single-layer geometries, the torus microreactor geometry brought on flow turbulence within the liquid along the curvatures inside the device channels, improving the efficiency of analyte-extractant contact and therefore leading to a high preconcentration factor. According to this design, the magnetic solid phase was held internally as a surface bed with the use of an 8 mm-diameter cylindric neodymium magnet, allowing the pass of a fixed volume of an arsenic aqueous standard solution. A preconcentration factor of up to 60 was found to reduce the typical "characteristic mass" (as sensitivity parameter) determined by direct measurement from 53.66 pg to 0.88 pg, showing an essential improvement in the arsenic signal sensitivity by absorption atomic spectrometry. This methodology emulates a miniaturized micro-solid-phase extraction system for flow-through water pretreatment samples in chemical analysis before coupling to techniques that employ reduced sample volumes, such as graphite furnace atomic absorption spectroscopy.

Long-term Efficacy and Tolerability of RPC4046 in an Open-Label Extension Trial of Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: The short-term efficacy of RPC4046, a monoclonal antibody against interleukin-13, has been shown in patients with eosinophilic esophagitis (EoE). We investigated the long-term efficacy and safety of RPC4046 in an open-label, long-term extension (LTE) study in adults with EoE. METHODS: We analyzed data from 66 patients who completed the 16-week, double-blind, induction portion of a phase 2 study of RPC4046 (180 mg or 360 mg/wk) vs placebo and then completed a 52-week LTE, receiving open-label RPC4046 360 mg/wk. The study was conducted at 28 centers in 3 countries; patients were enrolled between September 2014 and January 2017. Outcomes were stratified by double-blind dose group and included esophageal eosinophil counts, EoE endoscopic reference score, EoE histologic scoring system score, symptom-based EoE activity index score, and safety. RESULTS: By week 12 of the LTE, esophageal eosinophil mean and peak counts, total EoE endoscopic reference scores, and EoE histologic scoring system grade and stage scores did not differ considerably between patients who originally received placebo vs RPC4046. Most patients maintained responses through week 52. Symptom remission (symptom-based EoE activity index score, ≤20) increased from 14% at LTE entry to 67% at LTE week 52 in placebo‒RPC4046 patients and from 30% to 54% in RPC4046‒RPC4046 (either dose) patients. Of the 28 patients who did not have a histologic response to RPC4046 during the double-blind induction phase, 10 patients (36%) achieved response during the LTE. The most common adverse events were upper respiratory tract infection (21%) and nasopharyngitis (14%). CONCLUSIONS: One year of treatment with RPC4046 is generally well tolerated and results in continued improvement and/or maintenance of endoscopic, histologic, and clinical measures of EoE disease activity relative to baseline. TRIAL REGISTRATION: NCT02098473.

Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of individuals worldwide. Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection. Patients were confirmed by microbiological/serological testing, or on chest CT semiology. Available data on co-morbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed. A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes. A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis. In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease. Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%). Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi). Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type. Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004). Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%). In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas. Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis. The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043). Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality. We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

Listening to cities during the COVID-19 lockdown: How do human activities and urbanization impact soundscapes in Colombia?

Noise is one of the fastest growing and most ubiquitous type of environmental pollution, with prevalence in cities. The COVID-19 confinement in 2020 in Colombia led to a reduction in human activities and their associated noise. We used this unique opportunity to measure the impacts of noise on urban soundscapes, and explore the effects of urbanization intensity independently of human activity. We launched a community science initiative inviting participants to collect audio recordings from their windows using smartphones. Recordings were taken during severe mobility restrictions (April), and during a period of lightened restrictions (May-June). From the data collected, we measured changes in sound pressure levels (SPL), acoustic structure (soundscape spectro-temporal characteristics), and human perception between the two periods. A 12% increase in human activities had a detectable acoustic footprint, with a significant increase of SPL (2.15 dB, 128% increase), a shift towards dominance of low-frequency broadband signals, and a perceived dominance of human-made over wildlife sounds. Measured changes in SPL and acoustic structure were directly proportional to urbanization; however, perception of these changes was not. This gap may be associated with a masking effect generated by noise or a disconnect of humans from nature in large cities. The mobility restrictions created a chance to better understand the impacts of urbanization and human activities on the soundscape, while raising public awareness regarding noise pollution effects on people and wildlife. Information analyzed here might serve in urban planning in developing countries where urban expansion is occurring in a rapid, unplanned fashion.

An anti-IL-13 antibody reverses epithelial-mesenchymal transition biomarkers in eosinophilic esophagitis: Phase 2 trial results.

BACKGROUND: Fibrostenosis, the most serious eosinophilic esophagitis (EoE) complication, is mediated by epithelial-mesenchymal transition (EMT). Transitioned cells contribute to pathogenesis by overproducing extracellular matrix. OBJECTIVE: Our aim was to determine whether RPC4046 (anti‒IL-13 mAb) modulates EMT biomarkers in biopsy samples from adults with active EoE in a substudy of a double-blind, placebo-controlled phase 2 trial. METHODS: Baseline and week 16 esophageal biopsy samples were taken from 69 patients who were randomized to weekly treatment with subcutaneous RPC4046, 180 mg (n = 19), 360 mg (n = 26), or placebo (n = 24). Duplex immunofluorescence slides stained for E-cadherin and vimentin were digitally analyzed by mapping each epithelial cell and recording fluorescence intensities. End points included change from baseline to week 16 in percentage of vimentin-positive epithelial cells (primary), total E-cadherin expression, and vimentin-to-E-cadherin ratio per cell (an average of 47,000 cells per biopsy sample analyzed). RESULTS: The mean percentage of vimentin-positive cells decreased by 0.94%, 2.75%, and 4.24% in the placebo, low-dose, and high-dose groups, respectively (P =.032 for the high-dose vs placebo group). Mean E-cadherin expression per cell increased 5.6-fold in both dose groups versus in the placebo group (high-dose group P = .047). The increases in E-cadherin expression per cell from baseline to week 16 were correlated with improvements in histology, eosinophil counts, endoscopic findings, and symptoms. CONCLUSION: RPC4046 significantly reduced EMT markers in adults with active EoE, with greater effects at 360 mg. Together with results for eosinophil density and clinical end points from the main trial, these data support the hypothesis that pharmacologic IL-13 inhibition ameliorates both inflammatory and remodeling pathways and could potentially reduce the risk of fibrostenotic complications.

Both quiescent and proliferating cells circulate in the blood of the invasive apple snail Pomacea canaliculata.

Gastropod hematopoiesis occurs at specialized tissues in some species, but the evidence also suggests that hemocyte generation is maybe widespread in the connective tissues or the blood system in others. In Ampullariidae (Caenogastropoda), both the kidney and the lung contain putative hematopoietic cells, which react to immune challenges. In the current study, we wanted to explore if hematopoiesis occurs in the blood of Pomacea canaliculata. Thus, we obtained circulating hemocytes from donor animals and tested their ability to proliferate in the blood of conspecific recipients. We tracked cell proliferation by labeling the donors' hemocytes with the fluorescent cell proliferation marker carboxyfluorescein diacetate succinimidyl ester (CFSE). Transferred CFSE-labeled hemocytes survived and proliferated into the recipients' circulation for at least 17 days. We also determined the cell cycle status of circulating hemocytes by using the propidium iodide (PI) and acridine orange (AO) staining methods. Flow cytometry analyses showed that most PI-stained hemocytes were in the G1 phase (~96%), while a lower proportion of cells were through the G2/S-M transition (~4%). When we instead used AO-staining, we further distinguished a subpopulation of cells (~5%) of low size, complexity-granularity, and RNA content. We regarded this subpopulation as quiescent cells. In separate experimental sets, we complemented these findings by assessing in circulating hemocytes two evolutionary conserved features of quiescent, undifferentiated cells. First, we used JC-1 staining to determine the mitochondrial membrane potential (Ψm) of circulating hemocytes, which is expected to be low in quiescent cells. Most hemocytes (~87%) showed high aggregation of JC-1, which indicates a high Ψm. Besides that, a small hemocyte subpopulation (~11%) showed low aggregation of the dye, thus indicating a low Ψm. It is known that the transition from a quiescent to a proliferating state associates with an increase of the Ψm. The specificity of these changes was here controlled by membrane depolarization with the Ψm disruptor CCCP. Second, we stained hemocytes with Hoechst33342 dye to determine the efflux activity of ABC transporters, which participate in the multixenobiotic resistance system characteristic of undifferentiated cells. Most hemocytes (>99%) showed a low dye-efflux activity, but a small proportion of cells (0.06-0.12%) showed a high dye-efflux activity, which was significantly inhibited by 100 and 500 µM verapamil, and thus is indicative of an undifferentiated subpopulation of circulating hemocytes. Taken together, our results suggest that, among circulating hemocytes, there are cells with the ability to proliferate or to stay in a quiescent state and behave as progenitor cells later, either in the circulation or the hematopoietic tissues/organs.

Influence of the COVID-19 outbreak in people with epilepsy: Analysis of a Spanish population (EPICOVID registry).

BACKGROUND: The aim of this study was to have a better understanding of the influence of the coronavirus disease 2019 (COVID-19) pandemic in people with epilepsy (PWE) and to assess whether there have been changes in seizure control during the current COVID-19 outbreak, exploring the possible causes thereof. METHODS: This is an observational, retrospective study based on prospective data collection of 100 successive patients who attended an epilepsy outpatient clinic either face-to-face or telephonically during the months of the COVID-19 outbreak and national state of emergency. RESULTS: One hundred patients were included, 52% women, mean age 42.4 years. During the COVID-19 period, 27% of the patients presented an increase of >50% of seizure frequency. An increase of stress/anxiety (odds ratios (OR): 5.78; p = 0.008) and a prior higher seizure frequency (OR: 12.4; p = 0.001) were associated with worsening of seizures. Other risk factors were exacerbation of depression, sleep deprivation, less physical activity, and history of epilepsy surgery. Three patients had status epilepticus (SE) and one a cluster of seizures. Likewise, 9% of patients improved their seizure control. Reduction in stress/anxiety (OR: 0.05; p = 0.03) and recent adjustment of antiepileptics (OR: 0.07; p = 0.01) acted as protecting factors. CONCLUSIONS: A high proportion of PWE suffered a significant worsening of their seizure control during the months of the COVID-19 pandemic. Emotional distress due to home confinement was the main factor for the change in seizure control. Promoting physical activity and adequate sleep may minimize the potential impact of the pandemic in PWE. Ensuring correct follow-up can prevent decompensation in those PWE at high risk.

Key factors associated with uncontrolled asthma - the Asthma Control in Latin America Study.

Objective: This study aimed to estimate asthma control at specialist treatment centers in four Latin American countries and assess factors influencing poor asthma control.Methods: Patients aged ≥12 years with an asthma diagnosis and asthma medication prescription, followed at outpatient specialist centers in Argentina, Chile, Colombia, and Mexico, were included. The study received all applicable ethical approvals. The Asthma Control Test (ACT) was used to classify patients as having controlled (ACT 20-25) or uncontrolled (ACT ≤19) asthma. Frequency and statistical tests were used to assess the association between hospital admissions/exacerbations/emergency department (ED) visits and uncontrolled asthma; multivariate logistic regression was used to assess the association of uncontrolled asthma with clinical/demographic variables.Results: A total of 594 patients were included. Overall controlled-asthma prevalence was 43.4% (95% confidence interval [CI]: 39.0, 47.4). Patients with uncontrolled asthma were more likely to be women (adjusted odds ratio [aOR]: 1.85; p = 0.003), non-white (aOR: 2.14; p < 0.001), obese (aOR: 1.71; p = 0.036), to have a low monthly family income (aOR: 1.75; p = 0.004), to have severe asthma (aOR:1.59; p = 0.26), and, compared with patients with controlled asthma, to have a higher likelihood of asthma exacerbations (34.5% vs. 15.9%; p < 0.001), hospital admissions (6.9% vs. 3.1%; p = 0.042), and ED visits (34.5% vs. 15.9%; p < 0.001) due to asthma.Conclusions: Even in specialist ambulatory services, fewer than half of patients were classified as having controlled asthma. The proportion of uncontrolled patients varied according to clinical and demographic variables.

[Síndrome de Paget-Schrötter: presentación de cuatro casos]. / Paget-Schrötter syndrome: description of four cases.

Deep vein thrombosis (DVT) of the upper limb is a rare entity, estimated to account for 10% of all cases of DVT. Classically, they are classified into primary (idiopathic, due to subclavian vein compression or exercise related) and secondary (cancer, thrombophilia, trauma, shoulder surgery, associated to venous catheters or due to hormonal causes). The Paget- Schrötter syndrome is a primary thrombosis of the subclavian vein in the subclavian-axillary junction, related either to repetitive movements or to exercise; leading to microtrauma in the endothelium with consequent activation of the coagulation cascade. Clinically, it presents abruptly with pain, edema and feeling of heaviness in the affected limb. The treatment varies from thrombolytics and anticoagulation to surgical intervention, depending on the time of evolution. We present four cases of exercise-related subclavian vein thrombosis.

[Hospital morbidity and mortality in children with Down's syndrome: Experience in a university hospital in Chile]. / Morbimortalidad hospitalaria en niños con síndrome de Down.

INTRODUCTION: Children with Down's syndrome (DS) have a higher risk of congenital malformations and acute diseases, with increased risk of hospital admissions compared with the general population. This study describes patterns of hospital admissions for children and adolescents with DS. PATIENTS AND METHODS: A retrospective study of hospital admissions of children with DS, younger than 15 years old, and cared for by the Paediatric Department of the Hospital Clínico Pontificia Universidad Católica de Chile, between 2008 and 2011. RESULTS: There were 222 admissions of 161 patients with DS during the study period, of which 110 were girls. The median age was 8 months, and the median hospital stay was 6 days. Just over half (56.7%) of the hospital stays were in the Paediatric Critic Care Unit. Heart surgery was performed on 59.4%, and the principal congenital heart defect attended was atrioventricular canal. The principal diagnosis, other than heart surgery, was lower respiratory tract infection. In this series, 3 children died. CONCLUSIONS: Children with DS are a relevant group for inpatient care, because their high incidence in Chile, their respiratory and cardiovascular risk, prolonged hospitalizations, high frequency of critical care days and mortality risk. This group has special and complex needs during their hospitalizations and it is necessary to create a multidisciplinary team with competences to take care the particular characteristics of this vulnerable group.

Back pain as the initial presentation of subacute bacterial endocarditis in a patient with a complex medical history.

Infective endocarditis (IE) poses a diagnostic challenge due to its diverse clinical presentations, especially among high-risk groups. Diagnosis relies on integrating clinical presentation, blood cultures and imaging findings. Advanced imaging techniques enhance diagnostic accuracy, particularly in complex cases. Treatment involves antimicrobial therapy and surgery in complicated cases, with early intervention crucial for optimal outcomes. Coordinated care by an Endocarditis Team ensures tailored treatment plans, prompt complication management and long-term monitoring after discharge. The authors present a case of subacute IE presenting initially with back pain in a patient with a complex medical history, highlighting diagnostic and management approaches.

Structure and rheology of the polysaccharides from Schizymenia dubyi: Isolation of an unusual glucurono-carrageenan.

The system of polysaccharides from Schizymenia dubyi (Nemastomatales) was investigated. It contains a mixture of hybrid dl galactans (SH-S) and carrageenan-like polysaccharides, which were separated by means of precipitation with KCl at high concentrations. The structural features of the carrageenan-like fraction (SH-I) were investigated by methylation analysis, desulfation, uronic acid reduction, and NMR spectroscopy. It was concluded that the structure has the typical alternance α-(1 â†’ 3), ß-(1 â†’ 4) of d-galactose units, with most of the 3-linked units sulfated in O-2 (and some in O-4), and most of the 4-linked units sulfated in O-3, and substituted in O-2 by single stubs of ß-d-glucuronic acid (partly sulfated in each of the three available positions). This substituent has been only seldom found in red seaweed galactans. Rheological studies of 5 % and 10 % w/v SH, SH-S and SH-I aqueous systems, either without ions, or in KCl or CaCl2 solution gave thickening behaviors. Their random coil conformations justify the pseudoplastic behavior observed in the viscosity versus shear rate curves. As SH-S and SH-I are both contained in SH, an interpenetrating network could form in SH between the glucurono-carrageenan and the agaran, as inferred from the mechanical spectra recorded in water, especially with potassium ion.

Zweifach-Fung Microfluidic Device for Efficient Microparticle Separation: Cost-Effective Fabrication Using CO2 Laser-Ablated PMMA.

Microfluidic separators play a pivotal role in the biomedical and chemical industries by enabling precise fluid manipulations. Traditional fabrication of these devices typically requires costly cleanroom facilities, which limits their broader application. This study introduces a novel microfluidic device that leverages the passive Zweifach-Fung principle to overcome these financial barriers. Through Lagrangian computational simulations, we optimized an eleven-channel Zweifach-Fung configuration that achieved a perfect 100% recall rate for particles following a specified normal distribution. Experimental evaluations determined 2 mL/h as the optimal total flow rate (TFR), under which the device showcased exceptional performance enhancements in precision and recall for micrometer-sized particles, achieving an overall accuracy of 94% ± 3%. Fabricated using a cost-effective, non-cleanroom method, this approach represents a significant shift from conventional practices, dramatically reducing production costs while maintaining high operational efficacy. The cost of each chip is less than USD 0.90 cents and the manufacturing process takes only 15 min. The development of this device not only makes microfluidic technology more accessible but also sets a new standard for future advancements in the field.

Enhancing Magnetic Micro- and Nanoparticle Separation with a Cost-Effective Microfluidic Device Fabricated by Laser Ablation of PMMA.

Superparamagnetic iron oxide micro- and nanoparticles have significant applications in biomedical and chemical engineering. This study presents the development and evaluation of a novel low-cost microfluidic device for the purification and hyperconcentration of these magnetic particles. The device, fabricated using laser ablation of polymethyl methacrylate (PMMA), leverages precise control over fluid dynamics to efficiently separate magnetic particles from non-magnetic ones. We assessed the device's performance through Multiphysics simulations and empirical tests, focusing on the separation of magnetite nanoparticles from blue carbon dots and magnetite microparticles from polystyrene microparticles at various total flow rates (TFRs). For nanoparticle separation, the device achieved a recall of up to 93.3 ± 4% and a precision of 95.9 ± 1.2% at an optimal TFR of 2 mL/h, significantly outperforming previous models, which only achieved a 50% recall. Microparticle separation demonstrated an accuracy of 98.1 ± 1% at a TFR of 2 mL/h in both simulations and experimental conditions. The Lagrangian model effectively captured the dynamics of magnetite microparticle separation from polystyrene microparticles, with close agreement between simulated and experimental results. Our findings underscore the device's robust capability in distinguishing between magnetic and non-magnetic particles at both micro- and nanoscales. This study highlights the potential of low-cost, non-cleanroom manufacturing techniques to produce high-performance microfluidic devices, thereby expanding their accessibility and applicability in various industrial and research settings. The integration of a continuous magnet, as opposed to segmented magnets in previous designs, was identified as a key factor in enhancing magnetic separation efficiency.

Cardiopulmonary Exercise Testing in Heart Failure.

Cardiopulmonary exercise testing (CPET) provides important information for the assessment and management of patients with heart failure. This testing measures the respiratory and cardiac responses to exercise and allows measurement of the oxygen uptake (V˙O2) max and the relationship between minute ventilation (V˙E) and carbon dioxide excretion (V˙CO2). These two parameters help classify patients into categories that help predict prognosis, and patients with a V˙O2 < 14 mL/kg/min and V˙E/V˙CO2 slope >35 have a poor prognosis. This testing has been used in drug trials to determine complex physiologic responses to medications, such as angiotensin-converting enzyme inhibitors. For example, a study with enalapril demonstrated that the peak V˙O2 was 14.6 ± 1.6 mL/kg/min on placebo and 15.8 ± 2.0 mL/kg/min on enalapril after 15 days of treatment. The V˙E/V˙CO2 slopes were 43 ± 8 on placebo and 39 ± 7 on enalapril. Chronic heart failure and reduced physical activity measured by cardiopulmonary exercise testing are associated with increases in BNP, and several studies have demonstrated that cardiac rehabilitation is associated with reductions in BNP and increases in V˙O2. Therefore, BNP measurements can help determine the benefits of cardiac rehabilitation and provide indirect estimates of changes in V˙O2. In addition, measurement of microRNAs can determine the status of skeletal muscle used during physical activity and the changes associated with rehabilitation. However, CPET requires complicated technology, and simpler methods to measure physical activity could help clinicians to manage their patients. Recent advances in technology have led to the development of portable cardiopulmonary exercise testing equipment, which can be used in various routine physical activities, such as walking upstairs, sweeping the floor, and making the bed, to provide patients and clinicians a better understanding of the patient's current symptoms. Finally, current smart watches can provide important information about the cardiorespiratory system, identify unexpected clinical problems, and help monitor the response to treatment. The organized use of these devices could contribute to the management of certain aspects of these patients' care, such as monitoring the treatment of atrial fibrillation. This review article provides a comprehensive overview of the current use of CPET in heart failure patients and discusses exercise principles, methods, clinical applications, and prognostic implications.

Prevalence of musculoskeletal disorders among hotel housekeepers and cleaners: A systematic review with meta-analysis.

BACKGROUND: Musculoskeletal disorders (MSD) are among the most frequent and costly occupational health problems with a rising prevalence globally. OBJECTIVE: This systematic review with meta-analysis was conducted to know and evaluate the prevalence of MSD by anatomic location among hotel housekeepers (HHs) and cleaners. METHODS: Electronic searches were conducted in PubMed, Web of Science, Scopus, Dialnet Plus, PEDro and Cochrane Database for Systematic Reviews using a search strategy to identify cross-sectional studies reporting on the prevalence of MSD in HHs or cleaners. The risk of bias was assessed with Joanna Briggs Institute tool for systematic reviews. A random-effects model was used in the meta-analysis. RESULTS: Nineteen studies were included in the systematic review, nine of them in the meta-analysis (n = 2299). The study sample sizes ranged from 24 to 1043 participants. The Standardized Nordic Musculoskeletal Questionnaire was the most common tool used to assess MSD among both HHs and cleaners (9/19 of the included studies). The three most affected anatomic locations were the low back 53.9% (95% CI: 43.3-64.6), shoulders 41.4% (95% CI: 27.1-55.8), and wrists/hands 40.1% (95% CI: 24.5-55.7). CONCLUSIONS: HHs and cleaners have a high prevalence of MSD. Low back pain is the most prevalent MSD among both HHs and cleaners affecting up to one of two people.