Cyclic stretch enhances neutrophil extracellular trap formation.

BACKGROUND: Neutrophils, the most abundant leukocytes circulating in blood, contribute to host defense and play a significant role in chronic inflammatory disorders. They can release their DNA in the form of extracellular traps (NETs), which serve as scaffolds for capturing bacteria and various blood cells. However, uncontrolled formation of NETs (NETosis) can lead to excessive activation of coagulation pathways and thrombosis. Once neutrophils are migrated to infected or injured tissues, they become exposed to mechanical forces from their surrounding environment. However, the impact of transient changes in tissue mechanics due to the natural process of aging, infection, tissue injury, and cancer on neutrophils remains unknown. To address this gap, we explored the interactive effects of changes in substrate stiffness and cyclic stretch on NETosis. Primary neutrophils were cultured on a silicon-based substrate with stiffness levels of 30 and 300 kPa for at least 3 h under static conditions or cyclic stretch levels of 5% and 10%, mirroring the biomechanics of aged and young arteries. RESULTS: Using this approach, we found that neutrophils are sensitive to cyclic stretch and that increases in stretch intensity and substrate stiffness enhance nuclei decondensation and histone H3 citrullination (CitH3). In addition, stretch intensity and substrate stiffness promote the response of neutrophils to the NET-inducing agents phorbol 12-myristate 13-acetate (PMA), adenosine triphosphate (ATP), and lipopolysaccharides (LPS). Stretch-induced activation of neutrophils was dependent on calpain activity, the phosphatidylinositol 3-kinase (PI3K)/focal adhesion kinase (FAK) signalling and actin polymerization. CONCLUSIONS: In summary, these results demonstrate that the mechanical forces originating from the surrounding tissue influence NETosis, an important neutrophil function, and thus identify a potential novel therapeutic target.

Routine systematic prostate biopsies not replaced by magnetic resonance imaging-targeted biopsy.

Background: Multiparametric magnetic resonance imaging improves the performance of prostate cancer (PCa) diagnostics through a better selection of patients. Objectives: The aim of the study was to study the detection rate (DR) of systematic and targeted cognitive biopsies in a cohort with the previous negative systematic biopsies. A secondary objective was to describe the value of prostate-specific antigen density (PSAd) in the detection of clinically significant PCa (CSPCa). Methods: We designed a prospective, single-center, and comparative study to determine the DR of systematic and targeted cognitive biopsies. The clinical and pathological characteristics of each patient were described. Results: A total of 111 patients with Prostate Imaging Reporting and Data System lesions > 3 were included in the study. PCa was detected in 41.4% (46 of 111 patients); 42 (91.3%) were detected by systematic biopsy and 30 (65.2%) by targeted biopsy. CSPCa was detected in 26 (23.4%), 23 (88.5%) by systematic biopsy, and 21 (76.9%) by targeted biopsy. PSAd > 0.15 was directly associated with CSPCa. Conclusion: The detection of PCa by systematic biopsy in this series was higher than 80%; hence, its routine use should not be replaced by targeted biopsy, since it continues to be the cornerstone of the diagnosis in patients with prior negative biopsies.

Tunable Harmonic Flow Patterns in Microfluidic Systems through Simple Tube Oscillation.

Generation of tunable harmonic flows at low cost in microfluidic systems is a persistent and significant obstacle to this field, substantially limiting its potential to address major scientific questions and applications. This work introduces a simple and elegant way to overcome this obstacle. Harmonic flow patterns can be generated in microfluidic structures by simply oscillating the inlet tubes. Complex rib and vortex patterns can be dynamically modulated by changing the frequency and magnitude of tube oscillation and the viscosity of liquid. Highly complex rib patterns and synchronous vortices can be generated in serially connected microfluidic chambers. Similar dynamic patterns can be generated using whole or diluted blood samples without damaging the sample. This method offers unique opportunities for studying complex fluids and soft materials, chemical synthesis of various compounds, and mimicking harmonic flows in biological systems using compact, tunable, and low-cost devices.

The Transcription Factor SCX is a Potential Serum Biomarker of Fibrotic Diseases.

Fibrosing diseases are causes of morbidity and mortality around the world, and they are characterized by excessive extracellular matrix (ECM) accumulation. The bHLH transcription factor scleraxis (SCX) regulates the synthesis of ECM proteins in heart fibrosis. SCX expression was evaluated in lung fibroblasts and tissue derived from fibrotic disease patients and healthy controls. We also measured SCX in sera from 57 healthy controls, and 56 Idiopathic Pulmonary Fibrosis (IPF), 40 Hypersensitivity Pneumonitis (HP), and 100 Systemic Sclerosis (SSc) patients. We report high SCX expression in fibroblasts and tissue from IPF patients versus controls. High SCX-serum levels were observed in IPF (0.663 ± 0.559 ng/mL, p < 0.01) and SSc (0.611 ± 0.296 ng/mL, p < 0.001), versus controls (0.351 ± 0.207 ng/mL) and HP (0.323 ± 0.323 ng/mL). Serum levels of the SCX heterodimerization partner, TCF3, did not associate with fibrotic illness. IPF patients with severely affected respiratory capacities and late-stage SSc patients presenting anti-topoisomerase I antibodies and interstitial lung disease showed the highest SCX-serum levels. SCX gain-of-function induced the expression of alpha-smooth muscle actin (α-SMA/ACTA2) in fibroblasts when co-overexpressed with TCF3. As late and severe stages of the fibrotic processes correlated with high circulating SCX, we postulate it as a candidate biomarker of fibrosis and a potential therapeutic target.

Reconfigurable, Self-Sufficient Convective Heat Exchanger for Temperature Control of Microfluidic Systems.

Here, we demonstrate a modular, reconfigurable, and self-sufficient convective heat exchanger for regulation of temperature in microfluidic systems. The heat exchanger consists of polymer tubes wrapped around a plastic pole and fully embedded in an elastomer block, which can be easily mounted onto the microfluidic structure. It is compatible with various microfluidic geometries and materials. Miniaturized, battery-powered piezoelectric pumps are utilized to drive the heat carrying liquid through the heat exchanger at desired flow rates and temperatures. Customized temperature profiles can be generated by changing the configuration of the heat exchanger with respect to the microfluidic structure. Tailored dynamic temperature profiles can be generated by changing the temperature of the heat carrying liquid in successive cycles. This feature is used to study the calcium signaling of endothelial cells under successive temperature cycles of 24 to 37 °C. The versatility, simplicity, and self-sufficiency of the heat exchanger makes it suitable for various microfluidic based cellular assays.

Polysomnography-based diagnosis in Mexican adult patients with Obstructive Sleep Apnea Syndrome (OSAS) clinical suspicion.

INTRODUCTION: Obstructive sleep apnea syndrome (OSA) occurs in 2-4% of adults, increasing by 2.5 times the risk of sudden death. OBJECTIVE: Establish the concordance of the clinical diagnostic and electrical diagnosis in an adult series that underwent polysomnography. MATERIALS AND METHODS: Patients with sleep disorders that underwent consecutively polysomnography recording. RESULTS: In this study, 51 subjects from 24 to 77 years old (54.1±12.12) were included in the study; 23 males and 28 females; 78.43% were overweight or obese; 35.29% were smokers; 31.37% alcohol consumers; 47.05% hypertensive; 21% diabetics; 35.29% with airway alterations; 29.41% with depression; 13.72% dyslipidaemic and 7.84% with ischemic heart disease. Only 22 of the subjects qualified for OSA and the concordance between the clinical diagnostic and polysomnographic recording was 54% (Ko=0.60, Ke 0.50, Ka=0.20) with a 0.55 sensibility, 0.66 specificity, PPV 0.54, NPV 0.65, PLR 1.2, RVN 0.69 and PPP 0.47. The neck circumference in OSA was 40.68±5 vs. 37.7±3.5 cm. (p<0.02) and BMI was 36.48±13.16 vs 29.37±6.58 (p<0.008); male/female proportion was 1.8:1 (p<0.01), BMI was higher in OSA (p<0.002). The Epworth Sleepiness Scale did not discriminate between OSA and other sleep alteration (p<0.29). DISCUSSION AND CONCLUSIONS: We observed a poor agreement between clinical diagnosis and polysomnography. The Epworth Sleepiness Scale did not discern between OSA and other sleep disorders and finally there was no association with a systemic process.

Activated carbons from waste of oil-palm kernel shells, sawdust and tannery leather scraps and application to chromium(VI), phenol, and methylene blue dye adsorption.

Phenol, chromium, and dyes are continuously dumped into water bodies; the adsorption of these contaminants on activated carbon is a low-cost alternative for water remediation. We synthesized activated carbons from industrial waste of palm oil seed husks (kernel shells), sawdust, and tannery leather scraps. These materials were heated for 24 h at 600, 700 or 800°C, activated at 900°C with CO2 and characterized by proximate analysis and measurement of specific surface area (Brunauer-Emmett-Teller (BET) and Langmuir), and microporosity (t-plot). Isotherms showed micropores and mesopores in activated carbons. Palm seed activated carbon showed the highest fixed carbon content (96%), and Langmuir specific surface areas up to 1,268 m2/g, higher than those from sawdust (581 m2/g) and leather scraps (400 m2/g). The carbons were applied to adsorption of Cr(VI), phenol, and methylene blue dye from aqueous solutions. Phenol adsorption on activated carbons was 78-82 mg/g; on palm seed activated carbons, Cr(VI) adsorption at pH 7 was 0.35-0.37 mg/g, and methylene blue adsorption was 40-110 mg/g, higher than those from sawdust and leather scraps. Activated carbons from palm seed are promising materials to remove contaminants from the environment and represent an alternative application for vegetal wastes instead of dumping into landfills.

Early clinical effect of cladribine in patients with highly active multiple sclerosis in Mexico.

Background: Cladribine shows efficacy in multiple sclerosis (MS), but Latin American (LATAM) real-world data is limited, despite potential sociodemographic variations. Objective: Investigate baseline characteristics and clinical response in highly active MS patients in Mexico, identifying predictors of early treatment response. Method: A multicenter cohort study analyzed retrospective data from individuals with "highly active" MS in the Cladribine Patient Support Program across 11 Mexican clinics. Criteria included one-year prior treatment with another disease-modifying treatment and recent relapse with specific MRI findings. Primary outcomes focused on achieving NEDA-3 status after 12 months. Results: In the follow-up, 67.5% maintained NEDA-3 status. Baseline EDSS scores decreased significantly from 1.50 to 1.00 (p = 0.011), with no confirmed disability worsening. No significant differences were observed between NEDA-3 achievers and non-achievers in demographic and clinical variables. No severe adverse events were reported. Conclusion: Cladribine showed early and effective control of active MS in Mexican patients, demonstrating a secure profile with minimal adverse events. This study provides valuable real-world evidence in the LATAM context.

Corona With Lyme: A Long COVID Case Study.

The longevity of the coronavirus disease 2019 (COVID-19) pandemic has necessitated continued discussion about the long-term impacts of SARS-CoV-2 infection. Many who develop an acute COVID-19 infection will later face a constellation of enduring symptoms of varying severity, otherwise known as long COVID. As the pandemic reaches its inevitable endemicity, the long COVID patient population will undoubtedly grow and require improved recognition and management. The case presented describes the three-year arc of a previously healthy 26-year-old female medical student from initial infection and induction of long COVID symptomology to near-total remission of the disease. In doing so, the course of this unique post-viral illness and the trials and errors of myriad treatment options will be chronologized, thereby contributing to the continued demand for understanding this mystifying disease.

Studying the Synergistic Effect of Substrate Stiffness and Cyclic Stretch Level on Endothelial Cells Using an Elastomeric Cell Culture Chamber.

Endothelial cells lining blood vessels are continuously exposed to biophysical cues that regulate their function in health and disease. As we age, blood vessels lose their elasticity and become stiffer. Vessel stiffness alters the mechanical forces that endothelial cells experience. Despite ample evidence on the contribution of endothelial cells to vessel stiffness, less is known about how vessel stiffness affects endothelial cells. In this study, we developed a versatile model to study the cooperative effect of substrate stiffness and cyclic stretch on human aortic endothelial cells. We cultured endothelial cells on elastomeric wells covered with fibronectin-coated polyacrylamide gel. Varying the concentrations of acrylamide and bis-acrylamide enabled us to produce soft and stiff substrates with elastic modules of 40 and 200 kPa, respectively. Using a customized three-dimensional (3D) printed cam-driven system, the cells were exposed to 5 and 10% cyclic stretch levels. This enabled us to mimic the stiffness and stretch levels that endothelial cells experience in young and aged arteries. Using this model, we found that endothelial cells cultured on a soft substrate had minimal cytoskeletal alignment to the direction of the stretch compared to the ones cultured on the stiff substrate. We also observed an increase in the cellular area and aspect ratio in cells cultured on the stiff substrate, both of which are positively regulated by cyclic stretch. However, neither cyclic stretch nor substrate stiffness significantly affected the nuclear circularity. Additionally, we found that the accumulation of NF-κB in the nucleus, endothelial proliferation, tube formation, and expression of IL1ß depends on the stretch level and substrate stiffness. Our model can be further used to investigate the complex signaling pathways associated with vessel stiffening that govern the endothelial responses to mechanical forces.

Metabolic Diffusion in Neuropathologies: The Relevance of Brain-Liver Axis.

Chronic liver diseases include a broad group of hepatic disorders from different etiologies and with varying degrees of progression and severity. Among them, non-alcoholic fatty (NAFLD) and alcoholic (ALD) liver diseases are the most frequent forms of expression, caused by either metabolic alterations or chronic alcohol consumption. The liver is the main regulator of energy homeostasis and metabolism of potentially toxic compounds in the organism, thus hepatic disorders often promote the release of harmful substances. In this context, there is an existing interconnection between liver and brain, with the well-named brain-liver axis, in which liver pathologies lead to the promotion of neurodegenerative disorders. Alzheimer's (AD) and Parkinson's (PD) diseases are the most relevant neurological disorders worldwide. The present work highlights the relevance of the liver-related promotion of these disorders. Liver-related hyperammonemia has been related to the promotion of perturbations in nervous systems, whereas the production of ketone bodies under certain conditions may protect from developing them. The capacity of the liver of amyloid-ß (Aß) clearance is reduced under liver pathologies, contributing to the development of AD. These perturbations are even aggravated by the pro-inflammatory state that often accompanies liver diseases, leading to the named neuroinflammation. The current nourishment habits, named as Western diet (WD) and alterations in the bile acid (BA) profile, whose homeostasis is controlled by the liver, have been also related to both AD and PD, whereas the supplementation with certain compounds, has been demonstrated to alleviate the pathologies.

Motor cortico-nigral and cortico-entopeduncular information transmission and its modulation by buspirone in control and after dopaminergic denervation.

Cortical information is transferred to the substantia nigra pars reticulata (SNr) and the entopeduncular nucleus (EP), the output structures of the basal ganglia (BG), through three different pathways: the hyperdirect trans-subthalamic and the direct and indirect trans-striatal pathways. The nigrostriatal dopamine (DA) and the activation of 5-HT1A receptors, distributed all along the BG, may modulate cortical information transmission. We aimed to investigate the effect of buspirone (5-HT1A receptor partial agonist) and WAY-100635 (5-HT1A receptor antagonist) on cortico-nigral and cortico-entopeduncular transmission in normal and DA loss conditions. Herein, simultaneous electrical stimulation of the motor cortex and single-unit extracellular recordings of SNr or EP neurons were conducted in urethane-anesthetized sham and 6-hydroxydopamine (6-OHDA)-lesioned rats before and after drug administrations. Motor cortex stimulation evoked monophasic, biphasic, or triphasic responses, combination of an early excitation, an inhibition, and a late excitation in both the SNr and EP, while an altered pattern of evoked response was observed in the SNr after 6-OHDA lesion. Systemic buspirone potentiated the direct cortico-SNr and cortico-EP transmission in sham animals since increased duration of the inhibitory response was observed. In DA denervated animals, buspirone administration enhanced early excitation amplitude in the cortico-SNr transmission. In both cases, the observed effects were mediated via a 5-HT1A-dependent mechanism as WAY-100635 administration blocked buspirone's effect. These findings suggest that in control condition, buspirone potentiates direct pathway transmission and DA loss modulates responses related to the hyperdirect pathway. Overall, the results may contribute to understanding the role of 5-HT1A receptors and DA in motor cortico-BG circuitry functionality.

GC-MS of some lycorine-type Amaryllidaceae alkaloids.

The search for novel bioactive compounds and the identification of known ones in the plant kingdom are a challenge for the scientists working in different fields of plant science. In the recent years, mass spectrometry is the most frequently applied method for analysis of complex mixtures of plant metabolites. Twenty-two alkaloids of different lycorine skeleton subtypes (with a Δ3,4 double bond, with a Δ4,11 double bond, with saturated rings C and D, and with aromatic ring C) were subjected to separation with gas chromatography and studied with electron impact mass spectrometry including single quadropole (GC-EIMS), tandem mass (GC-EIMS/MS) and high resolution mass (EI-HRMS) detectors in order to determine their fragmentation pattern. The compounds showed excellent separation and specific MS fragmentation allowing structural determination. The GC-MS can be successfully applied for searching new and identification of known bioactive molecules, chemotaxonomical and chemoecological studies, among others, within the Amaryllidoideae subfamily.

Studying the Mechanobiology of Aortic Endothelial Cells Under Cyclic Stretch Using a Modular 3D Printed System.

Here, we describe a motorized cam-driven system for the cyclic stretch of aortic endothelial cells. Our modular design allows for generating customized spatiotemporal stretch profiles by varying the profile and size of 3D printed cam and follower elements. The system is controllable, compact, inexpensive, and amenable for parallelization and long-term experiments. Experiments using human aortic endothelial cells show significant changes in the cytoskeletal structure and morphology of cells following exposure to 5 and 10% cyclic stretch over 9 and 16 h. The system provides upportunities for exploring the complex molecular and cellular processes governing the response of mechanosensitive cells under cyclic stretch.

The effect of 5-HT1A receptor agonists on the entopeduncular nucleus is modified in 6-hydroxydopamine-lesioned rats.

BACKGROUND AND PURPOSE: l-DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5-HT1A receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus in rodents, seems to be involved in the etiopathology of l-DOPA-induced dyskinesia, we investigated whether the entopeduncular nucleus is modulated by the 5-HT1A receptor partial and full agonists, buspirone, and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in control and 6-hydroxydopamine (6-OHDA)-lesioned rats with or without long-term l-DOPA treatment. EXPERIMENTAL APPROACH: Extracellular single-unit electrocorticogram and local field potential recordings under anaesthesia, immunostaining assays and optogenetic manipulation coupled to electrophysiological recordings were performed. KEY RESULTS: Systemic buspirone reduced the entopeduncular nucleus firing rate in the sham animals and burst activity in the 6-OHDA-lesioned rats (with or without l-DOPA treatment), while local administration reduced entopeduncular nucleus activity in all the groups, regardless of DA integrity. Systemic 8-OH-DPAT also induced inhibitory effects only in the sham animals. Effects triggered by buspirone and 8-OH-DPAT were reversed by the 5-HT1A receptor antagonist, WAY-100635. Neither buspirone nor 8-OH-DPAT modified the low-frequency oscillatory activity in the entopeduncular nucleus or its synchronization with the motor cortex. Buspirone did not alter the response induced by subthalamic nucleus opto-stimulation in the entopeduncular nucleus. CONCLUSION AND IMPLICATIONS: Systemic 5-HT1A receptor activation elicits different effects on the electrophysiological properties of the entopeduncular nucleus depending on the integrity of the nigrostriatal pathway and it does not alter the relationship between subthalamic nucleus and entopeduncular nucleus neuron activity.

Neurological Manifestations and Outcomes in a Retrospective Cohort of Mexican Inpatients with SARS-CoV-2 Pneumonia: Design of a Risk Profile.

We analyzed the neurological manifestations in Mexican patients hospitalized with pneumonia due to COVID-19 and investigated the association between demographic, clinical, and biochemical variables and outcomes, including death. A retrospective, analytical study was conducted using the electronic records of patients hospitalized between 1 April 2020 and 30 September 2020. Records of 1040 patients were analyzed: 31.25% died and 79.42% had neurological symptoms, including headache (80.62%), anosmia (32.20%), ageusia (31.96%), myopathy (28.08%), disorientation (14.89%), encephalopathy (12.22%), neuropathy (5.4%), stroke (1.3%), seizures (1.3%), cerebral hemorrhage (1.08%), encephalitis (0.84%), central venous thrombosis (0.36%), and subarachnoid hemorrhage (0.24%). Patients also had comorbidities, such as hypertension (42.30%), diabetes mellitus (38.74%), obesity (61.34%), chronic obstructive pulmonary disease (3.17%), and asthma (2.01%). Factors associated with neurological symptoms were dyspnea, chronic obstructive pulmonary disease, advanced respiratory support, prolonged hospitalization, and worsening fibrinogen levels. Factors associated with death were older age, advanced respiratory support, amine management, chronic obstructive pulmonary disease, intensive care unit management, dyspnea, disorientation, encephalopathy, hypertension, neuropathy, diabetes, male sex, three or more neurological symptoms, and obesity grade 3. In this study we designed a profile to help predict patients at higher risk of developing neurological complications and death following COVID-19 infection.

The Noradrenergic System in Parkinson's Disease.

Nowadays it is well accepted that in Parkinson's disease (PD), the neurodegenerative process occurs in stages and that damage to other areas precedes the neuronal loss in the substantia nigra pars compacta, which is considered a pathophysiological hallmark of PD. This heterogeneous and progressive neurodegeneration may explain the diverse symptomatology of the disease, including motor and non-motor alterations. In PD, one of the first areas undergoing degeneration is the locus coeruleus (LC). This noradrenergic nucleus provides extensive innervation throughout the brain and plays a fundamental neuromodulator role, participating in stress responses, emotional memory, and control of motor, sensory, and autonomic functions. Early in the disease, LC neurons suffer modifications that can condition the effectiveness of pharmacological treatments, and importantly, can lead to the appearance of common non-motor symptomatology. The noradrenergic system also exerts anti-inflammatory and neuroprotective effect on the dopaminergic degeneration and noradrenergic damage can consequently condition the progress of the disease. From the pharmacological point of view, it is also important to understand how the noradrenergic system performs in PD, since noradrenergic medication is often used in these patients, and drug interactions can take place when combining them with the gold standard drug therapy in PD, L-3,4-dihydroxyphenylalanine (L-DOPA). This review provides an overview about the functional status of the noradrenergic system in PD and its contribution to the efficacy of pharmacological-based treatments. Based on preclinical and clinical publications, a special attention will be dedicated to the most prevalent non-motor symptoms of the disease.

6-Hydroxydopamine lesion and levodopa treatment modify the effect of buspirone in the substantia nigra pars reticulata.

BACKGROUND AND PURPOSE: l-DOPA-induced dyskinesia (LID) is considered a major complication in the treatment of Parkinson's disease (PD). Buspirone (5-HT1A partial agonist) have shown promising results in the treatment of PD and LID, however no 5-HT-based treatment has been approved in PD. The present study was aimed to investigate how the substantia nigra pars reticulata (SNr) is affected by buspirone and whether it is a good target to study 5-HT antidyskinetic treatments. EXPERIMENTAL APPROACH: Buspirone was studied using in vivo single-unit, electrocorticogram, local field potential recordings along with microdialysis and immunohistochemistry in naïve/sham, 6-hydroxydopamine (6-OHDA)-lesioned or 6-OHDA-lesioned and l-DOPA-treated (6-OHDA/l-DOPA) rats. KEY RESULTS: Local buspirone inhibited SNr neuron activity in all groups. However, systemic buspirone reduced burst activity in 6-OHDA-lesioned rats (with or without l-DOPA treatment), whereas 8-OH-DPAT, a full 5-HT1A agonist induced larger inhibitory effects in sham animals. Neither buspirone nor 8-OH-DPAT markedly modified the low-frequency oscillatory activity in the SNr or synchronization within the SNr with the cortex. In addition, local perfusion of buspirone increased GABA and glutamate release in the SNr of naïve and 6-OHDA-lesioned rats but no effect in 6-OHDA/l-DOPA rats. In the 6-OHDA/l-DOPA group, increased 5-HT transporter and decreased 5-HT1A receptor expression was found. CONCLUSIONS AND IMPLICATIONS: The effects of buspirone in SNr are influenced by dopamine loss and l-DOPA treatment. The present results suggest that the regulation of burst activity of the SNr induced by DA loss may be a good target to test new drugs for the treatment of PD and LID.

Adherence to self-administering interferon-ß1a using RebiSmart® device in Mexican patients with relapsing multiple sclerosis.

BACKGROUND: Adherence to disease-modifying therapies is determinant to attain maximal clinical benefit in multiple sclerosis (MS). RebiSmart® is an electronic auto-injector for subcutaneous delivery of interferon ß-1a (INF-ß1a) that monitors adherence by featuring a log of each drug administration for objective evaluation. The aim of this study was to assess long-term adherence to INF-ß1a by using the RebiSmart® device in Mexican patients with relapsing MS. METHODS: This is an observational multicenter study on patients with relapsing MS treated with INF-ß1a subcutaneously delivered by the RebiSmart® device. Adherence was computed as the number of injections received during the study period divided by the number of injections scheduled and expressed as percent. RESULTS: A total of 66 patients from 6 specialized MS centers were evaluated (45 females and 21 males, mean age 43.91±13.32 years). Mean adherence was 79.51±18% (median: 85.54%, range: 34.4-100%). During a median follow-up of 27.5 months (mean 33.36±29.39 months) the annualized relapse rate had a mean of 0.50±1.63. Mean initial EDSS was 1.90±1.52, and mean EDSS at the end of follow-up was 1.80±1.74. Compared with their counterparts, the mean number of relapses was significantly lower among patients with high (>80%) adherence (0.25±0.44 vs 0.67±92 relapses, respectively; P = 0.03). The proportion of relapse-free patients was 75.0% among patients with high adherence and 53.3% in low-compliant patients (P = 0.06). High adherence patients presented lower rates of EDSS worsening ≥1.0 at the end of treatment, as compared with low-compliant patients (11.1% vs 43.3%, respectively; P = 0.003). High schooling (>12 years) was the only predictor of a high adherence (OR: 2.97, 05% CI: 1.08-1.18; P = 0.03) and of being relapse-free during follow-up (OR: 3.22, 05% CI: 1.12-9.23; P = 0.03). CONCLUSION: Adherence to INF-ß1a using RebiSmart® in this Mexican cohort with MS was moderate, but associated with low relapse rate and influenced by high schooling.

Self-sufficient, low-cost microfluidic pumps utilising reinforced balloons.

Here, we introduce a simple method for increasing the inflation pressure of self-sufficient pressure pumps made of latex balloons. Our method involves reinforcing the latex balloon with elastane fibres to restrict the expansion of the balloon and increase its inflation pressure. This allowed us to increase the operational inflation pressure of a latex balloon from 2.5 to 25 kPa. Proof-of-concept experiments show the suitability of the reinforced balloon for inducing lateral forces and recirculating flows, which are employed for hydrodynamic capturing of large human monocytes. We also demonstrate the ability for the rapid exchange of solutions in repeated cycles upon manual squeezing of the reinforced balloons. We also show the suitability of the reinforced balloon for studying the mechanobiology of human aortic endothelial cells under various shear stress levels. The simplicity, portability, affordability, hyper-elasticity and scalability of the reinforced balloon pumps make them suitable for a wide range of microfluidic applications.