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1.
Am J Kidney Dis ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866126

RESUMO

Monkeypox (mpox) is an orthopoxviral zoonotic disease with a similar, but less severe, clinical presentation as smallpox. However, immunocompromised patients such as solid organ transplant recipients are at higher risk of developing severe forms of the disease. Herein, we describe the case of a 43 years-old female kidney transplant recipient that manifested severe skin ulcers alongside nodular lung opacities and pleural effusion attributed directly to the Monkeypox virus. Notwithstanding the initiation of early treatment with tecovirimat, a satisfactory response was not achieved until a reduction in immunosuppression to everolimus monotherapy, coupled with the transition to cidofovir for antiviral treatment. In conclusion, mpox has the potential to produce a severe form of systemic infection in individuals who have undergone solid organ transplantation, demanding a meticulous approach involving sequential antiviral treatment and modifications to immunosuppressive regimens in order to achieve complete healing.

2.
PLoS One ; 19(6): e0301223, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38837964

RESUMO

New immune checkpoints are emerging in a bid to improve response rates to immunotherapeutic drugs. The adenosine A2A receptor (A2AR) has been proposed as a target for immunotherapeutic development due to its participation in immunosuppression of the tumor microenvironment. Blockade of A2AR could restore tumor immunity and, consequently, improve patient outcomes. Here, we describe the discovery of a potent, selective, and tumor-suppressing antibody antagonist of human A2AR (hA2AR) by phage display. We constructed and screened four single-chain variable fragment (scFv) libraries-two synthetic and two immunized-against hA2AR and antagonist-stabilized hA2AR. After biopanning and ELISA screening, scFv hits were reformatted to human IgG and triaged in a series of cellular binding and functional assays to identify a lead candidate. Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics.


Assuntos
Antagonistas do Receptor A2 de Adenosina , Receptor A2A de Adenosina , Humanos , Animais , Receptor A2A de Adenosina/metabolismo , Receptor A2A de Adenosina/imunologia , Células HEK293 , Camundongos , Antagonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/farmacologia , Macaca fascicularis , Biblioteca de Peptídeos
3.
Front Cardiovasc Med ; 11: 1355037, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38836068

RESUMO

Background: Uncontrolled hypertension is a common problem worldwide, despite the availability of many effective antihypertensive drugs and lifestyle interventions. We assessed the efficacy of a multi-component intervention in individuals with uncontrolled hypertension in a primary care setting. Methods: This study was a randomized, multicenter, parallel, two-arm, single-blind controlled trial performed in primary healthcare centers in Mallorca (Spain). All participants were 35 to 75-years-old and had poorly controlled hypertension. Patients were randomly assigned in a 1:1 ratio to a control group (usual care) or an intervention group (self-monitoring of blood pressure, self-titration of hypertensive medications, dietary interventions, and physical activity interventions). The primary outcome was decrease in the mean SBP at 6 months relative to baseline. Results: A total of 153 participants were randomized to an intervention group (77) or a control group (76). After 6 months, the intervention group had a significantly lower systolic blood pressure (135.1 mmHg [±14.8] vs. 142.7 mmHg [±15.0], adjusted mean difference: 8.7 mmHg [95% CI: 3.4, 13.9], p < 0.001) and a significantly lower diastolic blood pressure (83.5 mmHg [±8.8] vs. 87.00 mmHg [±9.0], adjusted mean difference: 5.4 [95% CI: 2.9, 7.8], p < 0.0001). The intervention group also had significantly more patients who achieved successful blood pressure control (<140/90 mmHg; 54.4% vs. 32.9%, p = 0.011). Discussion: Self-monitoring of blood pressure in combination with self-management of hypertensive medications, diet, and physical activity in a primary care setting leads to significantly lower blood pressure in patients with poorly controlled hypertension.Clinical Trial Registration: ClinicalTrials.gov, identifier ISRCTN14433778.

4.
J Am Chem Soc ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888987

RESUMO

The membrane-bound hydrogenase (Mbh) from Pyrococcus furiosus is an archaeal member of the Complex I superfamily. It catalyzes the reduction of protons to H2 gas powered by a [NiFe] active site and transduces the free energy into proton pumping and Na+/H+ exchange across the membrane. Despite recent structural advances, the mechanistic principles of H2 catalysis and ion transport in Mbh remain elusive. Here, we probe how the redox chemistry drives the reduction of the proton to H2 and how the catalysis couples to conformational dynamics in the membrane domain of Mbh. By combining large-scale quantum chemical density functional theory (DFT) and correlated ab initio wave function methods with atomistic molecular dynamics simulations, we show that the proton transfer reactions required for the catalysis are gated by electric field effects that direct the protons by water-mediated reactions from Glu21L toward the [NiFe] site, or alternatively along the nearby His75L pathway that also becomes energetically feasible in certain reaction steps. These local proton-coupled electron transfer (PCET) reactions induce conformational changes around the active site that provide a key coupling element via conserved loop structures to the ion transport activity. We find that H2 forms in a heterolytic proton reduction step, with spin crossovers tuning the energetics along key reaction steps. On a general level, our work showcases the role of electric fields in enzyme catalysis and how these effects are employed by the [NiFe] active site of Mbh to drive PCET reactions and ion transport.

5.
Immunol Cell Biol ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873699

RESUMO

Antibiotic resistance is a major public health threat, and alternatives to antibiotic therapy are urgently needed. Immunotherapy, particularly the blockade of inhibitory immune checkpoints, is a leading treatment option in cancer and autoimmunity. In this study, we used a murine model of Salmonella Typhimurium infection to investigate whether immune checkpoint blockade could be applied to bacterial infection. We found that the immune checkpoint T-cell immunoglobulin and ITIM domain (TIGIT) was significantly upregulated on lymphocytes during infection, particularly on CD4+ T cells, drastically limiting their proinflammatory function. Blockade of TIGIT in vivo using monoclonal antibodies was able to enhance immunity and improve bacterial clearance. The efficacy of anti-TIGIT was dependent on the capacity of the antibody to bind to Fc (fragment crystallizable) receptors, giving important insights into the mechanism of anti-TIGIT therapy. This research suggests that targeting immune checkpoints, such as TIGIT, has the potential to enhance immune responses toward bacteria and restore antibacterial treatment options in the face of antibiotic resistance.

6.
ACS Omega ; 9(23): 25322-25331, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38882162

RESUMO

There is increasing awareness of epigenetics's importance in understanding disease etiologies and developing novel therapeutics. An increasing number of publications in the past few years reflect the renewed interest in epigenetic processes and their relationship with food chemicals. However, there needs to be a recent study that accounts for the most recent advances in the area by associating the chemical structures of food and natural product components with their biological activity. Here, we analyze the status of food chemicals and their intersection with natural products in epigenetic research. Using chemoinformatics tools, we compared quantitatively the chemical contents, structural diversity, and coverage in the chemical space of food chemicals with reported epigenetic activity. As part of this work, we built and curated a compound database of food and natural product chemicals annotated with structural information, an epigenetic target activity profile, and the main source of the food chemical or natural product, among other relevant features. The compounds are cross-linked with identifiers from other major public databases such as FooDB and the collection of open natural products, COCONUT. The compound database, the "Epi Food Chemical Database", is accessible in HTML and CSV formats at https://github.com/DIFACQUIM/Epi_food_Chemical_Database.

7.
Psychiatry Res ; 337: 115969, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772159

RESUMO

Maternal history of suicidal thoughts and behaviors (STBs) has been identified as a robust risk factor for offspring emotional and behavioral problems, including risk for offspring STBs. The impact of maternal history of STBs has been well-documented in adolescent and young adult samples, with emerging research highlighting the need to examine early clinical correlates of risk in young children, prior to the emergence of STBs. In an extension of prior work, the current study examined associations between maternal history of STBs and previously identified emotional and behavioral correlates of STBs (negative affect, internalizing problems, attention problems, aggressive behavior) in young children. These associations were examined in a mother-preschooler sample (n = 158, mean preschooler age=41.52 months) with approximately half of mothers endorsing a history of STBs and 20 % of the sample scoring at the threshold that indicates suicide risk. In multivariate models, maternal history of STBs was significantly associated with preschooler aggressive behavior, assessed via mother- (ß=0.19) and teacher-report (ß=0.21), as well as mother-reported negative affect (ß=0.22). Results document a link between maternal history of STBs and increased risk for heightened negative affect and aggressive behavior at home and school during the sensitive preschool period. Findings are discussed within the context of enhancing models of intergenerational transmission suicide risk.


Assuntos
Mães , Humanos , Feminino , Pré-Escolar , Masculino , Mães/psicologia , Adulto , Fatores de Risco , Suicídio/psicologia , Suicídio/estatística & dados numéricos , Ideação Suicida , Agressão/psicologia , Comportamento Problema/psicologia , Sintomas Afetivos/psicologia , Relações Mãe-Filho/psicologia , Filho de Pais com Deficiência/psicologia , Filho de Pais com Deficiência/estatística & dados numéricos , Transtornos do Comportamento Infantil/psicologia
8.
Front Immunol ; 15: 1363176, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629061

RESUMO

In recent years, in addition to the well-established role of T cells in controlling or promoting tumor growth, a new wave of research has demonstrated the active involvement of B cells in tumor immunity. B-cell subsets with distinct phenotypes and functions play various roles in tumor progression. Plasma cells and activated B cells have been linked to improved clinical outcomes in several types of cancer, whereas regulatory B cells have been associated with disease progression. However, we are only beginning to understand the role of a particular innate subset of B cells, referred to as B-1 cells, in cancer. Here, we summarize the characteristics of B-1 cells and review their ability to infiltrate tumors. We also describe the potential mechanisms through which B-1 cells suppress anti-tumor immune responses and promote tumor progression. Additionally, we highlight recent studies on the protective anti-tumor function of B-1 cells in both mouse models and humans. Understanding the functions of B-1 cells in tumor immunity could pave the way for designing more effective cancer immunotherapies.


Assuntos
Linfócitos B Reguladores , Neoplasias , Animais , Camundongos , Humanos , Linfócitos T , Imunidade , Imunoterapia
9.
J Asthma ; : 1-4, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38639468

RESUMO

INTRODUCTION: Mounier-Kuhn syndrome or tracheobronchomegaly, is a rare condition that consists of abnormal dilation of the trachea and main bronchi due to a pathological arrangement of smooth muscle fibers in this area. CASE REPORT: We present the case of a 46-year-old woman with poorly controlled asthma and recurrent infections, who was diagnosed with Mounier-Kuhn syndrome through a computed tomography scan revealing an unusual enlargement of the trachea with associated bronchiectasis. RESULTS: The diagnosis of Mounier-Kuhn syndrome is radiological, involving measurement of the trachea where a diameter >25 mm in men and >21 mm in women is observed. While diagnosis is sometimes incidental, there is an association with respiratory diseases such as asthma or COPD, hence clinical suspicion is important in patients with poorly controlled underlying conditions who present with recurrent infections, inadequate secretion management, or even hemoptysis. CONCLUSIONS: Despite its rarity, this syndrome significantly impacts patients' quality of life. Diagnosis and management involve comprehensive evaluations including computed tomography, with a multidisciplinary approach including pulmonologists and radiologists. Exploring its clinical features, associations with other respiratory diseases and treatment options is crucial in managing this rare respiratory condition.

10.
Front Immunol ; 15: 1385691, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605955

RESUMO

Mesenchymal stem/stromal cells (MSCs) are being increasingly used in cell-based therapies due to their broad anti-inflammatory and immunomodulatory properties. Intravascularly-administered MSCs do not efficiently migrate to sites of inflammation/immunopathology, but this shortfall has been overcome by cell surface enzymatic fucosylation to engender expression of the potent E-selectin ligand HCELL. In applications of cell-based therapies, cryopreservation enables stability in both storage and transport of the produced cells from the manufacturing facility to the point of care. However, it has been reported that cryopreservation and thawing dampens their immunomodulatory/anti-inflammatory activity even after a reactivation/reconditioning step. To address this issue, we employed a variety of methods to cryopreserve and thaw fucosylated human MSCs derived from either bone marrow or adipose tissue sources. We then evaluated their immunosuppressive properties, cell viability, morphology, proliferation kinetics, immunophenotype, senescence, and osteogenic and adipogenic differentiation. Our studies provide new insights into the immunobiology of cryopreserved and thawed MSCs and offer a readily applicable approach to optimize the use of fucosylated human allogeneic MSCs as immunomodulatory/anti-inflammatory therapeutics.


Assuntos
Imunomodulação , Células-Tronco Mesenquimais , Humanos , Glicosilação , Células-Tronco Mesenquimais/metabolismo , Criopreservação/métodos , Anti-Inflamatórios/metabolismo
11.
Cancers (Basel) ; 16(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38672593

RESUMO

Essential thrombocythemia (ET) is a blood cancer caused by mutations in JAK2 and CALR. It is widely recognized that both mutations lead to the constitutive activation of JAK2/STAT signaling, although other JAK/STAT-independent pathogenic mechanisms triggered by these alterations have also been described in ET. In an attempt to study JAK2/STAT-independent mechanisms derived from CALR mutations, our research group created a C. elegans model with patient-like mutations in calreticulin that lacks JAK counterparts. The introduction of patient-like mutations in the calreticulin of C. elegans leads to an increase in the transcriptional expression of nhr-2, independently of JAK2/STAT activation. In the present study, we aim to verify if this mechanism is conserved in patients with ET harboring CALR mutations. To do so, we evaluated the expression of potential orthologs of nhr-2 in human cell lines of interest for the study, as well as in bone marrow (BM) or peripheral blood (PB) mononuclear cells from patients with CALR or JAK2 mutations. The results revealed that this mechanism is conserved in CALR-mutated ET patients, since CALR, but not JAK2 mutations, were associated with an overexpression of RXRA in patients with ET. The use of drugs targeting the activation or blockade of this target in the analyzed cell lines did not result in changes in cell viability. However, RXRA might be relevant in the disease, pointing to the need for future research testing retinoids and other drugs targeting RXRα for the treatment of ET patients.

12.
Reprod Sci ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512699

RESUMO

While endometriosis is a common gynecologic disease associated with infertility, the psychosocial impact of endometriosis has not been evaluated against various quality of life (QoL) instruments and compared with other chronic illnesses. We rigorously analyzed the psychosocial burden of endometriosis in adult women and compared standardized and validated QoL scores of women with and without endometriosis, before and following treatment, and against other chronic illnesses. We searched PubMed, PsychINFO Embase, and Cochrane Reviews and ClinicalTrials.gov from January 1990 to December 2022 for publications using a detailed list of search terms related to QoL, endometriosis, and questionnaires. Only English-language publications that evaluated the association between Endometriosis and QoL using standardized and validated questionnaires measured at baseline and following treatment were considered. Four reviewers first performed a title and abstract screening followed by full text-review to finalize included articles. QoL scores of women with endometriosis were measured at baseline and analyzed against women without endometriosis and women with endometriosis who had undergone treatment. Additionally, baseline endometriosis scores were assessed against the published QoL scores of populations with other chronic conditions. Assessment of risk of bias was performed in accordance with Cochrane and Newcastle-Ottawa Scale guidelines. A total of 30 articles were included in this review: 4 randomized trials and 26 observational studies. The diagnosis and experience of women with symptomatic endometriosis had an equal or worse QoL score than that of other chronic conditions including heart disease, diabetes, and breast cancer when compared using the 36-Item Short Form Survey and World Health Organization Quality of Life questionnaires. Evidence showed association between low QoL and infertility, sexual dysfunction, mental health struggles, physical pain, poor sleep and fatigue. QoL scores were lower at baseline compared to following treatment in the majority of these domains. Endometriosis is associated with significant psychosocial burden and impaired QoL scores across baseline measurements in comparison to controls and other chronic illnesses. Medical and surgical interventions significantly decreased experienced burdens and improved QoL of women with endometriosis.

13.
Curr Dev Nutr ; 8(Suppl 1): 102027, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38476725

RESUMO

Populations in low- and middle-income countries (LMIC) typically consume less than the recommended daily amount of protein. Alternative protein (AP) sources could help combat malnutrition, but this requires careful consideration of elements needed to further establish AP products in LMIC. Key considerations include technological, nutritional, safety, social, and economic challenges. This perspective analyzes these considerations in achieving dietary diversity in LMIC, using a combination of traditional and novel protein sources with high nutritional value, namely, soy, mycoprotein, and cultivated meat. Technological approaches to modulate the technofunctionality and bitter off-tastes of plant-sourced proteins facilitate processing and ensure consumer acceptance. Economic considerations for inputs, infrastructure for production, and transportation represent key elements to scale up AP. Dietary diversification is indispensable and LMIC cannot rely on plant proteins alone to provide adequate protein intake sustainably. Investments in infrastructure and innovation are urgently needed to offer diverse sources of protein in LMIC.

14.
Brain Spine ; 4: 102717, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510633

RESUMO

Introduction: In the first part of this White Paper, the European Association of Neurosurgical Societies (EANS) Diversity in Neurosurgery Committee (DC) addressed the obstacles faced by neurosurgeons when planning to have a family and practice during pregnancy, attempting to enumerate potential, easily implementable solutions for departments to be more family-friendly and retain as well as foster talent of parent-neurosurgeons, regardless of their gender identity and/or sexual orientation. Attrition avoidance amongst parent-neurosurgeons is at the heart of these papers. Research question: In this second part, we address the obstacles posed by practice with children and measures to mitigate attrition rates among parent-neurosurgeons. For the methodology employed to compose this White Paper, please refer to Supplementary Electronic Materials (SEM) 1. Materials and methods: For composing these white papers, the European Association of Neurosurgical Societies (EANS)'s Diversity Committee (DC) recruited neurosurgeon volunteers from all member countries, including parents, aspiring parents, and individuals without any desire to have a family to create a diverse and representative working group (WG). Results: In spite of the prevailing heterogeneity in policies across the continent, common difficulties can be identified for both mothers and fathers considering the utilization of parental leave. Discussion and conclusion: Reconciliation of family and a neurosurgical career is challenging, especially for single parents. However, institutional support in form of childcare facilities and/or providers, guaranteed lactation breaks and rooms, flexible schedule models including telemedicine, and clear communication of policies can improve working conditions for parent-neurosurgeons, avoid their attrition, and foster family-friendly work environments.

15.
Physiol Behav ; 278: 114522, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38492909

RESUMO

BACKGROUNDS: Sleep restriction is considered a stressful condition itself, causing a wide variety of physiological alterations, from cognitive and hormonal to immunological status. In addition, it is established that stress in mother rats can modify milk ejection, milk composition, and maternal care of the pups. Also, sleep disturbances during the early stages of motherhood are a common feature of all studied species. In this context, while the impacts of sleep disruption in non-lactating animals were extensively investigated, its repercussions during the initial phases of motherhood have been poorly explored. Therefore, we wonder if maternal behavior, milk ejection and its macronutrient composition would be disrupted when mother rats are subjected to an additional acute or chronic sleep restriction to the already existing sleep disturbances. METHODS: Lactating rats were implanted with unilateral electrodes for polysomnographic recordings and for deep brain electrical stimulation into mesopontine waking-promoting area (for sleep deprivation). During the early postpartum period (postpartum day 5-9), mother rats were randomly assigned into one of three groups: chronic sleep restriction group (CSR; 6 h of sleep deprivation/day for five consecutive days), acute sleep restriction group (ASR; 6 h of sleep deprivation only for one day), or undisturbed group (control group). Active maternal behaviors (retrievals of the pups into the nest, mouthing, lickings [corporal and anogenital] and sniffing the pups) and passive maternal behaviors (kyphotic and supine nursing postures) were evaluated during a 30 min period without sleep restriction immediately after the sleep restriction or control period. The litter weight gain was assessed every day, and on the last experimental session mothers were milked for posterior macronutrients analysis (protein, carbohydrates and fat). RESULTS: When compared to control group, CSR decreased the amount of milk ejected in the middle days of the sleep restriction period, while ASR did not affect this parameter. Moreover, ASR reduced milk protein content compared to control and CSR groups. Finally, compared to the control group, CSR reduced active maternal behaviors towards the end of the treatment days. CONCLUSIONS: We demonstrated that not only acute but also chronic sleep restriction impacts on the postpartum period, each one affecting different aspects of maternal behavior and lactation. Our results suggest the existence of a homeostatic recovery mechanism in breastfeeding during CSR, possibly ensuring the survival of the litter, while the decline in active maternal behaviors appears to be cumulative.


Assuntos
Lactação , Privação do Sono , Feminino , Humanos , Ratos , Animais , Lactação/fisiologia , Sono/fisiologia , Período Pós-Parto , Comportamento Materno/fisiologia , Nutrientes
16.
Anal Chem ; 96(15): 5790-5797, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38452224

RESUMO

Nanoplastic particles are emerging as an important class of environmental pollutants in the atmosphere that have adverse effects on our ecosystems and human health. While many methods have been developed to quantitatively detect nanoplastics; however, sensitive detection at low concentrations in a complex environment remains elusive. Herein, we demonstrate a greener method to fabricate a surface-enhanced Raman spectroscopy (SERS) substrate consisting of self-assembled plasmonic Ag-Au bimetallic nanoparticle (NP) films for quantitative SERS detection of nanoplastics in complex media. The self-assembly of Ag-Au bimetallic NPs was achieved through thermal evaporation onto a vapor-phase compatible ionic liquid based on deep eutectic solvent over the growth substrate. The finite-difference time-domain simulation revealed that the localized field enhancement is strong in the gaps, which generate uniform SERS "hotspots" in the obtained substrate. Benefiting from highly accessible SERS "hotspots" at the gaps, the SERS substrate exhibits excellent sensitivity for detecting crystal violet with a limit of detection (LOD) as low as 10-14 M and excellent reproducibility (RSD of 5.8%). The SERS substrate is capable of detecting PET nanoplastics with LOD as low as 1 µg/mL and about 100 µg/mL in real samples such as tap water, lake water, diluted milk, and wine. Moreover, we also validated the feasibility of the designed SERS substrate for the practical detection of PET nanoplastics collected from commercial drinking water bottles, and it showed great potential applications for sensitive detection in actual environments.

17.
Neurol Sci ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38494461

RESUMO

BACKGROUND: This study sought to determine whether intensive blood pressure (BP) control for patients with successful reperfusion following acute ischemic stroke (AIS) is beneficial, compared to conventional BP management. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCTs) on the subject. The studied outcomes included dependency or death at 90 days (modified Rankin Scale [mRS] 3-6); severe disability at 90 days (mRS 3-5); mortality at 90 days; and symptomatic intracranial hemorrhage. Odds ratios (OR) with 95% confidence intervals were used to compare the treatment effects for categorical outcomes. We employed a fixed-effect model for analyses with low heterogeneity (I2 < 25%) and a random-effects model for analyses with higher heterogeneity. RESULTS: A total of 1519 patients were included, with 50% (n = 760) receiving intensive BP control (systolic BP < 140 mmHg). Functional disability or death at 90 days was significantly higher in the intensive group (54.9%) compared to the conventional treatment group (44.1%) (OR = 1.51; 95% Confidence Interval [CI]: 1.15-1.96; p = 0.003; I2 = 29%). Severe functional disability (mRS 3-5) was significantly higher in the intensive group (30.6% vs. 43.5%, OR = 1.75; 95%CI = 1.36-2.25; p < 0.0001; I2 = 0%). There was no difference in symptomatic intracranial hemorrhage (OR = 1.13; 95%CI = 0.76-1.67) or mortality (OR = 1.22; 95%CI = 0.9-1.64). CONCLUSIONS: Intensive BP control is harmful in patients who underwent EVT for AIS and achieved successful reperfusion. It yields higher rates of functional dependence, with no differences in mortality or symptomatic intracranial hemorrhage.

18.
Sci Rep ; 14(1): 7388, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548829

RESUMO

Intrahospital transfer (IHT), a routine in the management of neurocritical patients requiring imaging or interventions, might affect brain metabolism. Studies about IHT effects using microdialysis (MD) have produced conflicting results. In these studies, only the most damaged hemisphere was monitored, and those may not reflect the impact of IHT on overall brain metabolism, nor do they address differences between the hemispheres. Herein we aimed to quantify the effect of IHT on brain metabolism by monitoring both hemispheres with bilateral MD. In this study, 27 patients with severe brain injury (10 traumatic brain injury and 17 subarachnoid hemorrhage patients) were included, with a total of 67 IHT. Glucose, glycerol, pyruvate and lactate were measured by MD in both hemispheres for 10 h pre- and post-IHT. Alterations in metabolite levels after IHT were observed on both hemispheres; although these changes were more marked in hemisphere A (most damaged) than B (less damaged). Our results suggest that brain metabolism is altered after an IHT of neurocritical ill patients particularly but not limited to the damaged hemisphere. Bilateral monitorization may be more sensitive than unilateral monitorization for detecting metabolic disturbances not directly related to the course of the disease.


Assuntos
Hemorragia Subaracnóidea , Humanos , Microdiálise/métodos , Hemorragia Subaracnóidea/terapia , Hemorragia Subaracnóidea/metabolismo , Ácido Láctico/metabolismo , Ácido Pirúvico/metabolismo , Encéfalo/metabolismo
19.
Lab Chip ; 24(8): 2358-2359, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38501991

RESUMO

Correction for 'Integrated biosensors for monitoring microphysiological systems' by Lei Mou et al., Lab Chip, 2022, 22, 3801-3816, https://doi.org/10.1039/D2LC00262K.

20.
Arch Cardiol Mex ; 94(2): 161-168, 2024 02 12.
Artigo em Espanhol | MEDLINE | ID: mdl-38346327

RESUMO

Objective: To determine the impact of diabetes on cardiovascular risk in patients with dyslipidemia. Method: Observational, cross-sectional and comparative study in which cardiovascular risk was determined at 10 years in 100 patients with dyslipidemia, of these, 50 non-diabetic patients and 50 diabetic patients. Results: Both groups had similar characteristics in terms of age, blood pressure figures, average body mass index, and HDL and LDL levels. It was observed that the diabetic group has almost double the risk compared to the dyslipidemia group, 13.7 vs. 7.9 (p = 0.014), and the calculated heart age is also higher in patients with diabetes, 80 vs. 66 years (p = 0.003). Even in patients with diabetes there is a greater difference between the real age and the age of the heart, 24 years vs. 15 years of patients without diabetes (p = 0.000). Conclusion: Having diabetes and dyslipidemia doubles the cardiovascular risk of patients. Little metabolic control was found in the population studied, which significantly increases complications at an early age and the economic burden on the health system and the families of patients, so it is necessary to rethink treatment strategies to improve metabolic control and with it the prognosis for the patient in the long term.


Objetivo: Determinar el impacto de la diabetes en el riesgo cardiovascular en pacientes con dislipidemia. Método: Estudio observacional, transversal y comparativo, en el que se determinó el riesgo cardiovascular en 100 pacientes con dislipidemia, de los cuales 50 eran diabéticos, sin complicaciones crónicas. Resultados: Ambos grupos tenían características similares en cuanto a edad, presión arterial, índice de masa corporal, niveles de c-HDL y c-LDL. Sin embargo, al comparar el porcentaje de riesgo cardiovascular, observamos que el grupo de diabéticos tenía casi el doble de riesgo cardiovascular, 13.7 contra 7.9 (p = 0.014), y la edad del corazón calculada también fue mayor en los pacientes con diabetes, 80 contra 66 años (p = 0.003). Incluso, en los pacientes diabéticos la diferencia entre la edad real y la edad del corazón fue mayor, 24 años contra 15 años (p = 0.000). Conclusión: Padecer diabetes y dislipidemia duplica el riesgo cardiovascular. En la población estudiada se encontró poco control metabólico, lo que aumenta significativamente las complicaciones en edades tempranas y la carga económica al sistema de salud y a las familias de los pacientes; por tanto, es necesario replantear las estrategias de tratamiento para mejorar el control metabólico y el pronóstico del paciente a largo plazo.

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