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1.
bioRxiv ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38948818

ABSTRACT

Conductive hydrogels have gained interest in biomedical applications and soft electronics. To tackle the challenge of ionic hydrogels falling short of desired mechanical properties in previous studies, our investigation aimed to understand the pivotal structural factors that impact the conductivity and mechanical behavior of polyethylene glycol (PEG)-based hydrogels with ionic conductivity. Polyether urethane diacrylamide (PEUDAm), a functionalized long-chain macromer based on PEG, was used to synthesize hydrogels with ionic conductivity conferred by incorporating ions into the liquid phase of hydrogel. The impact of salt concentration, water content, temperature, and gel formation on both mechanical properties and conductivity was characterized to establish parameters for tuning hydrogel properties. To further expand the range of conductivity available in these ionic hydrogels, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) was incorporated as a single copolymer network or double network configuration. As expected, conductivity in these ionic gels was primarily driven by ion diffusivity and charge density, which was dependent on hydrogel network formation and swelling. Copolymer network structure had minimal effect on the conductivity which was primarily driven by counter-ion equilibrium; however, the mechanical properties and equilibrium swelling was strongly dependent on network structure. The structure-property relationships elucidated here enables the rationale design of this new double network hydrogel to achieve target properties for a broad range of applications.

2.
Neurosurgery ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949385

ABSTRACT

BACKGROUND AND OBJECTIVES: Inflammation is a key pathomechanism for growth and rupture of intracranial aneurysms. Anti-inflammatory mechanisms may reduce rupture of intracranial aneurysms and the incidence of aneurysmal subarachnoid hemorrhage (SAH). Ultraviolet (UV) radiation from sunlight exposure induces systemic anti-inflammatory responses through immunosuppressive mechanisms. We studied whether SAH incidence is associated with UV radiation. METHODS: Global SAH incidence, time trends, and regional differences from 32 countries were linked to UV radiation data from the Tropospheric Emission Monitoring Internet Service. Odds between low vs high UV exposure and SAH incidence were calculated. Correlation analysis was performed using R (R 4.1.2). RESULTS: SAH incidences ranged from 1.3 to 27 per 100 000 patient-years (p-y) and UV index from 1.76 to 11.27. The correlation coefficient (rho) between SAH incidence and UV index was -0.48 (P = .012). SAH incidence was highest in Japan (13.7-27.9 p-y) with an UV index 6.28. UV index was highest in Chile 11.27 with a lower SAH incidence (3.8-4.8 p-y). The lowest UV index 1.76 was seen in Iceland with higher SAH incidence (9.8 p-y).Within Europe, regions with higher UV indices reported lower SAH incidences (Northwest Europe: SAH incidence p-y 8.61/UV index 2.85; Southeast Europe: SAH incidence p-y 7.37/UV index 4.65) with a significant inverse correlation (rho = -0.68, P = .004) and not a significant correlation between non-European countries (rho = -0.43, P = .19). Low exposure of UV radiation in global regions predicted higher than median incidences of SAH with an odds ratio 5.13 (95% CIs 1.02-31.5). CONCLUSION: The incidence of SAH is inversely associated with UV radiation. Further studies should assess the actual UV exposure in relation to SAH incidence and potential biological explanations for the relation we found.

3.
Parasitol Res ; 123(6): 254, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38922478

ABSTRACT

The Americas hold the greatest bird diversity worldwide. Likewise, ectoparasite diversity is remarkable, including ticks of the Argasidae and Ixodidae families - commonly associated with birds. Considering that ticks have potential health implications for humans, animals, and ecosystems, we conducted a systematic review to evaluate the effects of bioclimatic, geographic variables, and bird species richness on tick infestation on wild birds across the Americas. We identified 72 articles that met our inclusion criteria and provided data on tick prevalence in wild birds. Using Generalized Additive Models, we assessed the effect of environmental factors, such as habitat type, climatic conditions, bird species richness, and geographic location, on tick infestation. Our findings show that most bird infestation case studies involved immature ticks, such as larvae or nymphs, while adult ticks represented only 13% of case studies. We found birds infested by ticks of the genera Amblyomma (68%), Ixodes (22%), Haemaphysalis (5%), Dermacentor (1%), and Rhipicephalus (0.8%) in twelve countries across the Americas. Our findings revealed that temperature variation and bird species richness were negatively associated with tick infestation, which also varied with geographic location, increasing in mid-latitudes but declining in extreme latitudes. Our results highlight the importance of understanding how environmental and bird community factors influence tick infestation in wild birds across the Americas and the dynamics of tick-borne diseases and their impact on biodiversity.


Subject(s)
Bird Diseases , Birds , Tick Infestations , Animals , Tick Infestations/veterinary , Tick Infestations/epidemiology , Tick Infestations/parasitology , Birds/parasitology , Americas/epidemiology , Bird Diseases/parasitology , Bird Diseases/epidemiology , Animals, Wild/parasitology , Ecosystem , Ticks/physiology , Ticks/classification , Biodiversity , Environment , Prevalence
4.
Parasitol Res ; 123(6): 252, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38922536

ABSTRACT

Avian haemosporidians of the genera Plasmodium and Haemoproteus are a group of widely distributed blood parasites that can negatively affect the fitness of their hosts. Colombia contains the greatest diversity of birds on the planet, but knowledge about the associations between haemosporidian and its avifauna is scarce and fragmented. We collected blood samples from 255 birds (203 residents and 52 neotropical migrants) belonging to 27 families and 108 species. The study was conducted in six localities in the inter-Andean valleys of the Cauca and Magdalena rivers. Parasites of the genera Plasmodium and Haemoproteus were identified in the samples by morphological and molecular analysis of a fragment of the mitochondrial gene cyt b. Among the samples, 9.3% (n = 24) were positive for Plasmodium or Haemoproteus. Co-infection with Plasmodium and Haemoproteus was found in Red-eyed Vireo. Seventeen haemosporidian lineages were identified, five of which were reported for the first time in resident birds (Common Ground Dove, Checker-throated Stipplethroat, Tropical Kingbird, Pale-breasted Thrush, and Ruddy-breasted Seedeater) and one in the Summer Tanager (neotropical migrant). The research results confirm the wide diversity of haemosporidian present in tropical lowlands and the possible role of neotropical migratory birds in dissemination on haemosporidian along their migratory routes.


Subject(s)
Bird Diseases , Birds , Haemosporida , Plasmodium , Protozoan Infections, Animal , Animals , Colombia/epidemiology , Haemosporida/classification , Haemosporida/isolation & purification , Haemosporida/genetics , Birds/parasitology , Bird Diseases/parasitology , Bird Diseases/epidemiology , Plasmodium/classification , Plasmodium/isolation & purification , Plasmodium/genetics , Protozoan Infections, Animal/parasitology , Protozoan Infections, Animal/epidemiology , Cytochromes b/genetics , Animal Migration , Phylogeny , Coinfection/parasitology , Coinfection/veterinary , Coinfection/epidemiology
5.
Nat Commun ; 15(1): 5425, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926339

ABSTRACT

Synthetic biology allows us to reuse, repurpose, and reconfigure biological systems to address society's most pressing challenges. Developing biotechnologies in this way requires integrating concepts across disciplines, posing challenges to educating students with diverse expertise. We created a framework for synthetic biology training that deconstructs biotechnologies across scales-molecular, circuit/network, cell/cell-free systems, biological communities, and societal-giving students a holistic toolkit to integrate cross-disciplinary concepts towards responsible innovation of successful biotechnologies. We present this framework, lessons learned, and inclusive teaching materials to allow its adaption to train the next generation of synthetic biologists.


Subject(s)
Synthetic Biology , Synthetic Biology/education , Synthetic Biology/methods , Humans , Biotechnology/education , Students/psychology
6.
J Funct Morphol Kinesiol ; 9(2)2024 May 31.
Article in English | MEDLINE | ID: mdl-38921632

ABSTRACT

Cardiac deaths account for the largest share of on-duty firefighter deaths. To help ensure duty fitness and minimize injury risk, many fire departments require the passing of an annual physical ability test, consisting of a battery of simulated fire suppression activities (sFSAs). The purpose of the study was to determine the relationship of sFSA performance to acute cardiac and respiratory events (ACREs) and the effect that estimated VO2max has on sFSA performance. The study was retrospective. As part of an annual physical ability test, five timed sFSAs were performed, summed for a composite time, and categorized into three performance levels (fast, moderate, and slow). Estimated VO2max was determined using the Forestry Step Test. A significant (p = 0.023) linear trend was observed with higher sFSA performance times being associated with a higher proportion of firefighters going on to suffer an ACRE. The estimated VO2max was significantly (p < 0.001) higher in the fast group compared to the slow group. There was not a significant (p = 0.70) difference in estimated VO2max between the moderate and slow groups. Estimated VO2max performance and sFSA performance were significantly correlated, with rs(488) = -0.272 and p < 0.001. Poorer sFSA performance was found to be associated with a higher proportion of ACREs. The results suggest that sFSA performance may be a valid indicator of ACRE injury risk and aerobic capacity.

7.
PLoS One ; 19(6): e0305846, 2024.
Article in English | MEDLINE | ID: mdl-38923996

ABSTRACT

Can a political party spend enough across electoral campaigns to garner a majority within the U.S. Congress? Prior research on campaign spending minimizes the importance of campaign heterogeneity and fails to aggregate effects across campaigns, rendering it unable to address this question. Instead, we tackle the question with a system-level analysis of campaign expenditures. First, using a flexible machine learning approach, we show that spending has substantial and nonlinear marginal effects on outcomes at the level of the campaign. Second, by aggregating these effects to the entire U.S. Congress, we show that large seat swings that change congressional control have, in the past, been possible for expenditure levels consonant with those presently observed after having removed the most extreme levels. However, this possibility appears to have faded over the past decade. Our approach also allows us to illustrate the often significant effects that eliminating campaign spending could have.


Subject(s)
Politics , United States , Humans , Machine Learning
8.
Neurobiol Lang (Camb) ; 5(2): 288-314, 2024.
Article in English | MEDLINE | ID: mdl-38832358

ABSTRACT

Approximately 7% of children have developmental language disorder (DLD), a neurodevelopmental condition associated with persistent language learning difficulties without a known cause. Our understanding of the neurobiological basis of DLD is limited. Here, we used FreeSurfer to investigate cortical surface area and thickness in a large cohort of 156 children and adolescents aged 10-16 years with a range of language abilities, including 54 with DLD, 28 with a history of speech-language difficulties who did not meet criteria for DLD, and 74 age-matched controls with typical language development (TD). We also examined cortical asymmetries in DLD using an automated surface-based technique. Relative to the TD group, those with DLD showed smaller surface area bilaterally in the inferior frontal gyrus extending to the anterior insula, in the posterior temporal and ventral occipito-temporal cortex, and in portions of the anterior cingulate and superior frontal cortex. Analysis of the whole cohort using a language proficiency factor revealed that language ability correlated positively with surface area in similar regions. There were no differences in cortical thickness, nor in asymmetry of these cortical metrics between TD and DLD. This study highlights the importance of distinguishing between surface area and cortical thickness in investigating the brain basis of neurodevelopmental disorders and suggests the development of cortical surface area to be of importance to DLD. Future longitudinal studies are required to understand the developmental trajectory of these cortical differences in DLD and how they relate to language maturation.

9.
Immunohorizons ; 8(6): 464-477, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38922288

ABSTRACT

PD-1 blockade has been approved for head and neck squamous cell carcinoma (HNSCC) patients. However, many HNSCC patients do not respond to this treatment, and other tumor microenvironmental factors may promote resistance to PD-1 blockade. We previously identified increased expression of the inhibitory receptor NKG2A on CD8+ T cells in HNSCC tumors compared with T cells in matching PBMC samples. Mechanisms that promote NKG2A expression and the role of NKG2A on human T cells in the tumor microenvironment, however, are uncertain. In this study, we show that tumor-conditioned media (TCM) of HNSCC cancer cell lines or ascites fluid from colorectal carcinoma patients is sufficient to induce the expression of NKG2A and other inhibitory receptors on activated CD8+ T cells isolated from PBMCs of healthy donors. Boiling or small molecular mass cutoff filtering did not eliminate the effect of TCM, suggesting that a small molecule promotes NKG2A. T cell activation in TCM decreased the basal and maximal mitochondrial respiration to metabolically restrain CD8+ T cells. Functionally, T cell activation in TCM reduced CD8+ T cell cytotoxicity as shown by lower production of cytokines, granzyme B, and perforin. Furthermore, TCM prevented CD8+ T cells from killing cancer cells in response to an anti-CD19/anti-CD3 bispecific T cell engager. Thus, a small secreted molecule from HNSCC cells can induce NKG2A expression and promote T cell dysfunction. Our findings may lead to targets for novel cancer therapies or biomarkers for NKG2A blockade response and provide a model to study T cell dysfunction and impaired metabolism.


Subject(s)
CD8-Positive T-Lymphocytes , NK Cell Lectin-Like Receptor Subfamily C , Squamous Cell Carcinoma of Head and Neck , Humans , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , NK Cell Lectin-Like Receptor Subfamily C/metabolism , NK Cell Lectin-Like Receptor Subfamily C/immunology , Cell Line, Tumor , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Culture Media, Conditioned/pharmacology , Tumor Microenvironment/immunology , Lymphocyte Activation/immunology , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology
10.
Res Sq ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38746448

ABSTRACT

AI tools intend to transform mental healthcare by providing remote estimates of depression risk using behavioral data collected by sensors embedded in smartphones. While these tools accurately predict elevated symptoms in small, homogenous populations, recent studies show that these tools are less accurate in larger, more diverse populations. In this work, we show that accuracy is reduced because sensed-behaviors are unreliable predictors of depression across individuals; specifically the sensed-behaviors that predict depression risk are inconsistent across demographic and socioeconomic subgroups. We first identified subgroups where a developed AI tool underperformed by measuring algorithmic bias, where subgroups with depression were incorrectly predicted to be at lower risk than healthier subgroups. We then found inconsistencies between sensed-behaviors predictive of depression across these subgroups. Our findings suggest that researchers developing AI tools predicting mental health from behavior should think critically about the generalizability of these tools, and consider tailored solutions for targeted populations.

11.
Front Immunol ; 15: 1404846, 2024.
Article in English | MEDLINE | ID: mdl-38774881

ABSTRACT

Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and regulating cellular functions. Vesicle trafficking of lysosomes and LROs are critical to maintain their functions. The lysosomal trafficking regulator (LYST) is an elusive protein important for the regulation of membrane dynamics and intracellular trafficking of lysosomes and LROs. Mutations to the LYST gene result in Chédiak-Higashi syndrome, an autosomal recessive immunodeficiency characterized by defective granule exocytosis, cytotoxicity, etc. Despite eight decades passing since its initial discovery, a comprehensive understanding of LYST's function in cellular biology remains unresolved. Accumulating evidence suggests that dysregulation of LYST function also manifests in other disease states. Here, we review the available literature to consolidate available scientific endeavors in relation to LYST and discuss its relevance for immunomodulatory therapies, regenerative medicine and cancer applications.


Subject(s)
Lysosomes , Vesicular Transport Proteins , Humans , Lysosomes/metabolism , Vesicular Transport Proteins/metabolism , Vesicular Transport Proteins/genetics , Animals , Chediak-Higashi Syndrome/genetics , Protein Transport , Mutation
12.
13.
Neurosci Lett ; 834: 137845, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38821202

ABSTRACT

Sepsis-associated encephalopathy, which manifests in severe cognitive and depressive symptoms, is directly linked to neuroinflammation. Our study investigates the efficacy of 25H-NBOMe, a phenethylamine, in alleviating these symptoms, potentially offering an innovative treatment for post-sepsis depression. Wistar rats, weighing between 250-300 g, were subjected to cecal ligation and puncture (CLP) surgery to induce sepsis. Depressive-like behaviors were assessed using the forced swim test (FST) on either day 7 or 14 post-surgery, to establish the presence of depressive symptoms. The impact of 25H-NBOMe treatment was then evaluated, focusing on the head-twitch response (HTR), performance in the FST, and GFAP expression in the prefrontal cortex. Treatment with 25H-NBOMe resulted in significant behavioral changes, demonstrated by decreased immobility and increased swimming times in the FST, along with a rise in the HTR. These outcomes indicate a reduction in depressive-like symptoms post-sepsis and the psychoactive effects of the compound. Furthermore, a notable decrease in GFAP expression in the study highlights the compound's impact on mitigating sepsis-induced astrogliosis. This study demonstrates the effectiveness of 25H-NBOMe, a psychedelic in the phenethylamine class, in treating post-sepsis depression and reducing astrogliosis. However, the psychedelic nature of 25H-NBOMe calls for further investigation into similar compounds with less psychoactive impact, crucial for advancing treatment options for neuropsychiatric symptoms following sepsis.


Subject(s)
Depression , Rats, Wistar , Sepsis , Animals , Male , Sepsis/complications , Sepsis/drug therapy , Sepsis/metabolism , Sepsis/psychology , Depression/drug therapy , Depression/etiology , Rats , Hallucinogens/pharmacology , Hallucinogens/therapeutic use , Phenethylamines/pharmacology , Phenethylamines/therapeutic use , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Sepsis-Associated Encephalopathy/drug therapy , Sepsis-Associated Encephalopathy/metabolism
14.
Eur Radiol ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806803

ABSTRACT

OBJECTIVES: Arterial calcification is thought to protect against rupture of intracranial aneurysms, but studies in a representative population of intracranial aneurysm patients have not yet been performed. The aim was to compare the prevalence of aneurysm wall calcification and intracranial carotid artery calcification (ICAC) between patients with an unruptured intracranial aneurysm (UIA) and a ruptured intracranial aneurysm (RIA). MATERIALS AND METHODS: We matched 150 consecutive UIA patients to 150 RIA patients on age and sex. Aneurysm wall calcification and ICAC were quantified on non-contrast enhanced computed tomography images with the modified Agatston score. We compared the prevalence of aneurysm wall calcification, ICAC, and severe ICAC (defined as a modified Agatston score in the fourth quartile) between UIA and RIA patients using univariate and multivariate conditional logistic regression models adjusted for aneurysm characteristics and cardiovascular risk factors. RESULTS: Aneurysm wall calcification was more prevalent in UIA compared to RIA patients (OR 5.2, 95% CI: 2.0-13.8), which persisted after adjustment (OR 5.9, 95% CI: 1.7-20.2). ICAC prevalence did not differ between the two groups (crude OR 0.9, 95% CI: 0.5-1.8). Severe ICAC was more prevalent in UIA patients (OR 2.0, 95% CI: 1.1-3.6), but not after adjustment (OR 1.0, 95% CI: 0.5-2.3). CONCLUSIONS: Aneurysm wall calcification but not ICAC was more prevalent in UIAs than in RIAs, which corresponds to the hypothesis that calcification may protect against aneurysmal rupture. Aneurysm wall calcification should be further assessed as a predictor of aneurysm stability in prospective cohort studies. CLINICAL RELEVANCE STATEMENT: Calcification of the intracranial aneurysm wall was more prevalent in unruptured than ruptured intracranial aneurysms after adjustment for cardiovascular risk factors. Calcification may therefore protect the aneurysm against rupture, and aneurysm wall calcification is a candidate predictor of aneurysm stability. KEY POINTS: Aneurysm wall calcification was more prevalent in patients with unruptured than ruptured aneurysms, while internal carotid artery calcification was similar. Aneurysm wall calcification but not internal carotid artery calcification is a candidate predictor of aneurysm stability. Cohort studies are needed to assess the predictive value of aneurysm wall calcification for aneurysm stability.

15.
Protein Sci ; 33(6): e4991, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38757381

ABSTRACT

The de novo design of miniprotein inhibitors has recently emerged as a new technology to create proteins that bind with high affinity to specific therapeutic targets. Their size, ease of expression, and apparent high stability makes them excellent candidates for a new class of protein drugs. However, beyond circular dichroism melts and hydrogen/deuterium exchange experiments, little is known about their dynamics, especially at the elevated temperatures they seemingly tolerate quite well. To address that and gain insight for future designs, we have focused on identifying unintended and previously overlooked heat-induced structural and chemical changes in a particularly stable model miniprotein, EHEE_rd2_0005. Nuclear magnetic resonance (NMR) studies suggest the presence of dynamics on multiple time and temperature scales. Transiently elevating the temperature results in spontaneous chemical deamidation visible in the NMR spectra, which we validate using both capillary electrophoresis and mass spectrometry (MS) experiments. High temperatures also result in greatly accelerated intrinsic rates of hydrogen exchange and signal loss in NMR heteronuclear single quantum coherence spectra from local unfolding. These losses are in excellent agreement with both room temperature hydrogen exchange experiments and hydrogen bond disruption in replica exchange molecular dynamics simulations. Our analysis reveals important principles for future miniprotein designs and the potential for high stability to result in long-lived alternate conformational states.


Subject(s)
Hot Temperature , Nuclear Magnetic Resonance, Biomolecular , Molecular Dynamics Simulation , Protein Conformation , Proteins/chemistry , Protein Stability
16.
Neurology ; 102(12): e209169, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38788175

ABSTRACT

BACKGROUND AND OBJECTIVES: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. METHODS: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). RESULTS: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). DISCUSSION: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.


Subject(s)
Antifibrinolytic Agents , Subarachnoid Hemorrhage , Tranexamic Acid , Humans , Tranexamic Acid/therapeutic use , Tranexamic Acid/administration & dosage , Subarachnoid Hemorrhage/drug therapy , Female , Antifibrinolytic Agents/therapeutic use , Antifibrinolytic Agents/administration & dosage , Male , Middle Aged , Treatment Outcome , Aged , Prospective Studies , Adult
17.
Bioengineering (Basel) ; 11(5)2024 May 09.
Article in English | MEDLINE | ID: mdl-38790340

ABSTRACT

In this paper, we propose a daily living situation where objects in a kitchen can be grasped and stored in specific containers using a virtual robot arm operated by different myoelectric control modes. The main goal of this study is to prove the feasibility of providing virtual environments controlled through surface electromyography that can be used for the future training of people using prosthetics or with upper limb motor impairments. We propose that simple control algorithms can be a more natural and robust way to interact with prostheses and assistive robotics in general than complex multipurpose machine learning approaches. Additionally, we discuss the advantages and disadvantages of adding intelligence to the setup to automatically assist grasping activities. The results show very good performance across all participants who share similar opinions regarding the execution of each of the proposed control modes.

18.
J Med Virol ; 96(5): e29674, 2024 May.
Article in English | MEDLINE | ID: mdl-38757834

ABSTRACT

Human Papillomaviruses (HPV) are a diverse family of non-enveloped dsDNA viruses that infect the skin and mucosal epithelia. Persistent HPV infections can lead to cancer frequently involving integration of the virus into the host genome, leading to sustained oncogene expression and loss of capsid and genome maintenance proteins. Microhomology-mediated double-strand break repair, a DNA double-stranded breaks repair pathway present in many organisms, was initially thought to be a backup but it's now seen as vital, especially in homologous recombination-deficient contexts. Increasing evidence has identified microhomology (MH) near HPV integration junctions, suggesting MH-mediated repair pathways drive integration. In this comprehensive review, we present a detailed summary of both the mechanisms underlying MH-mediated repair and the evidence for its involvement in HPV integration in cancer. Lastly, we highlight the involvement of these processes in the integration of other DNA viruses and the broader implications on virus lifecycles and host innate immune response.


Subject(s)
Carcinogenesis , Papillomaviridae , Papillomavirus Infections , Humans , Papillomaviridae/pathogenicity , Papillomaviridae/genetics , Papillomaviridae/physiology , Papillomavirus Infections/virology , Papillomavirus Infections/complications , Virus Integration , DNA Repair , DNA Breaks, Double-Stranded , DNA, Viral/genetics
19.
Heliyon ; 10(10): e30556, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38770298

ABSTRACT

Background: The etiopathogenesis of autoimmune diseases is multifactorial, including hormonal factors. Remission of autoimmunity has been observed following treatment for concomitant hyperparathyroidism. Additionally, patients with autoimmune diseases have shown increased expression of parathyroid hormone receptor (PTH1R) and altered distribution of B cells subsets. Hence, this study aims to evaluate potential mechanisms and in vitro effects of PTH stimulation on B lymphocytes. Methods: Using the human B-cell line Ramos (RA.1), various biological effects were evaluated with and without parathyroid hormone (PTH) stimulation at varying concentrations. Flow cytometry was employed to evaluate the phenotype of B lymphocytes based on IgD and CD38 expression, apoptosis induction via Annexin V and proliferation using CFSE. IgM production was quantified through ELISA, and Western blot analysis was performed to assess syk protein phosphorylation as an indicator of cell activation. Results: Ramos cells (RA.1) evidenced a statistically significant change in the phenotype under human PTH stimulation, demonstrating an increased proportion of germinal centre cells (Bm3-Bm4) when stimulated with high concentrations of PTH. Conclusions: The in vitro effects of PTH in B cells subsets align with previous findings of an altered phenotype in B lymphocytes expressing PTH1R among autoimmune disease patients, suggesting a potential role of this hormone in the pathophysiology of autoimmune diseases. However, further studies are necessary to elucidate the mechanisms by which PTH generates observed effects in B lymphocytes and to determine if PTH plays a role in autoimmunity.

20.
bioRxiv ; 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38712252

ABSTRACT

The initial objective of this study was to shed light on the evolution of small DNA tumor viruses by analyzing de novo assemblies of publicly available deep sequencing datasets. The survey generated a searchable database of contig snapshots representing more than 100,000 Sequence Read Archive records. Using modern structure-aware search tools, we iteratively broadened the search to include an increasingly wide range of other virus families. The analysis revealed a surprisingly diverse range of chimeras involving different virus groups. In some instances, genes resembling known DNA-replication modules or known virion protein operons were paired with unrecognizable sequences that structural predictions suggest may represent previously unknown replicases and novel virion architectures. Discrete clades of an emerging group called adintoviruses were discovered in datasets representing humans and other primates. As a proof of concept, we show that the contig database is also useful for discovering RNA viruses and candidate archaeal phages. The ancillary searches revealed additional examples of chimerization between different virus groups. The observations support a gene-centric taxonomic framework that should be useful for future virus-hunting efforts.

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