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1.
Annu Rev Physiol ; 84: 533-558, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-34780258

RESUMO

Urinary tract infection (UTI) is the most common type of urogenital disease. UTI affects the urethra, bladder, ureter, and kidney. A total of 13.3% of women, 2.3% of men, and 3.4% of children in the United States will require treatment for UTI. Traditionally, bladder (cystitis) and kidney (pyelonephritis) infections are considered independently. However, both infections induce host defenses that are either shared or coordinated across the urinary tract. Here, we review the chemical and biophysical mechanisms of bacteriostasis, which limit the duration and severity of the illness. Urinary bacteria attempt to overcome each of these defenses, complicating description of the natural history of UTI.


Assuntos
Cistite , Infecções Urinárias , Sistema Urinário , Criança , Cistite/complicações , Cistite/microbiologia , Feminino , Humanos , Rim , Masculino
2.
Am J Epidemiol ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38918039

RESUMO

There is a dearth of safety data on maternal outcomes after perinatal medication exposure. Data-mining for unexpected adverse event occurrence in existing datasets is a potentially useful approach. One method, the Poisson tree-based scan statistic (TBSS), assumes that the expected outcome counts, based on incidence of outcomes in the control group, are estimated without error. This assumption may be difficult to satisfy with a small control group. Our simulation study evaluated the effect of imprecise incidence proportions from the control group on TBSS' ability to identify maternal outcomes in pregnancy research. We simulated base case analyses with "true" expected incidence proportions and compared these to imprecise incidence proportions derived from sparse control samples. We varied parameters impacting Type I error and statistical power (exposure group size, outcome's incidence proportion, and effect size). We found that imprecise incidence proportions generated by a small control group resulted in inaccurate alerting, inflation of Type I error, and removal of very rare outcomes for TBSS analysis due to "zero" background counts. Ideally, the control size should be at least several times larger than the exposure size to limit the number of false positive alerts and retain statistical power for true alerts.

3.
J Vasc Surg ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944400

RESUMO

OBJECTIVES: The frequency of atherectomy in lower extremity arterial disease has increased substantially over the past several years, specifically in the office-based laboratory (OBL) setting, yet the efficacy compared to other interventions and the consequences of distal embolization remain unknown. Embolic Protection Devices (EPD) have been used at varying rates depending on physician and practice setting. Previous studies have described lesion characteristics to consider when weighing the benefits and drawbacks associated with device usage. Our study focuses on the use of atherectomy and EPD in femoropopliteal arterial disease to better characterize resource usage trends and postoperative outcomes in the inpatient and OBL interventional settings. METHODS: We conducted a retrospective analysis on endovascular interventions performed for femoral-popliteal occlusive disease that were entered into the Vascular Quality Initiative (VQI) data registry between 2017-2021. A 1:1 greedy-match, adjusted analysis based on inpatient or OBL location of procedure was utilized to compare the groups. Hierarchical logistical regression with selective use of principal component analysis was utilized to further explore the differences in EPD usage and immediate postoperative outcomes. A proportional hazard model was used to demonstrate differences in reintervention rates up to two years postoperatively between patients who underwent atherectomy in the inpatient vs OBL treatment setting. RESULTS: 2,849 matched pairs were included in the final analysis. In our cohort, there was 22% EPD usage overall, 40% in the hospital setting and 4.4% in the OBL setting (p<0.001). Among the patients with available follow-up information, OBL intervention setting increased probability of reintervention by 18% at 2 years postoperatively compared to the inpatient setting, however there was no difference associated with EPD placement and rate of reintervention. CONCLUSIONS: Use of EPD in the OBL setting compared to the hospital setting is dramatically decreased, however, no increased incidence of postoperative complications was seen compared to procedures performed in the hospital setting when controlling for patient and lesion characteristics. Patients with available follow-up data were more likely to undergo ipsilateral reintervention between 6 months and 2 years postoperatively if atherectomy was done in the OBL setting. Dedicated studies are encouraged to ensure patient safety, effective resource allocation, and long-term efficacy of OBL atherectomy as an ever-growing number of peripheral arterial procedures are transitioned to the OBL setting.

4.
Eur J Clin Microbiol Infect Dis ; 43(4): 659-671, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38277032

RESUMO

PURPOSE: Vast majority of helminth diseases remain neglected tropical diseases (NTDs), causing significant morbidity. The widespread and periodic distribution of antiparasitic drugs, remains the cornerstone for controlling these diseases. In Spain, most helminthiasis cases are imported, and suspicion and diagnosis have become increasingly important. Our primary objective is to present the epidemiological landscape of helminthiasis diagnoses within our facility, while also detailing the demographic characteristics of the affected population. METHODS: A retrospective study was conducted at the Hospital Universitario Severo Ochoa (HUSO) from January 1, 2007, to December 31, 2020, encompassing all diagnosed cases of helminthiasis during this period. Comprehensive epidemiological, clinical, and microbiological data were gathered for all diagnosed patients. The study population comprised patients receiving treatment at the HUSO, as well as those receiving treatment at the Leganés and Fuenlabrada Primary Care Units. Subsequently, descriptive and comparative statistics were performed, comparing Spanish and foreign patients. RESULTS: During this period, a total of 952 patients were diagnosed with some form of helminthiasis. Among them, 495 were Spanish, and 457 were foreign. The total number of helminths identified, including patients with multiple infections, was 1,010. Significant differences were observed between Africans and Americans in terms of age distribution, with a higher prevalence among Africans in the 0-15 age range and among Americans in the 31-60 age range. Variations were noted in the distribution of helminths, with S. stercoralis significantly affecting Americans. For Spanish patients, the presence of Trichuris trichiura and S. stercoralis was significantly associated with eosinophilia, whereas among foreign patients, it was associated with Trichuris trichiura, Ascaris lumbricoides among others. Regarding symptoms, skin manifestations were more frequent among Spanish, while digestive were more common among foreigners. CONCLUSIONS: This study offers crucial epidemiological insights into helminth infections observed over time in a Madrid hospital. Although the prevalence of helminth infections has been decreasing, there is still a need for screening and diagnosing foreign patients.


Assuntos
Helmintíase , Helmintos , Animais , Humanos , Fezes/parasitologia , Helmintíase/epidemiologia , Helmintíase/tratamento farmacológico , Helmintíase/parasitologia , Prevalência , Estudos Retrospectivos , Espanha/epidemiologia , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade
5.
Purinergic Signal ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587723

RESUMO

Intestinal low-grade inflammation induced by a high-fat diet has been found to detonate chronic systemic inflammation, which is a hallmark of obesity, and precede the apparition of insulin resistance, a key factor for developing type 2 diabetes (T2D). Aberrant purinergic signaling pathways have been implicated in the pathogenesis of inflammatory bowel disease and other gastrointestinal diseases. However, their role in the gut inflammation associated with obesity and T2D remains unexplored. C57BL/6 J mice were fed a cafeteria diet for 21 weeks and received one injection of streptozotocin in their sixth week into the diet. The gene expression profile of purinergic signaling components in colon tissue was assessed by RT-qPCR. Compared to control mice, the treated group had a significant reduction in colonic length and mucosal and muscular layer thickness accompanied by increased NF-κB and IL-1ß mRNA expression. Furthermore, colonic P2X2, P2X7, and A3R gene expression levels were lower, while the P2Y2, NT5E, and ADA expression levels increased. In conclusion, these data suggest that these purinergic signaling components possibly play a role in intestinal low-grade inflammation associated with obesity and T2D and thus could represent a novel therapeutic target for the treatment of the metabolic complications related to these diseases.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38866224

RESUMO

OBJECTIVE: To analyze the psychometric properties of the Pictorial Pain Interference Questionnaire (PPIQ) for evaluating functional interference in the population with chronic low back pain (CLBP). DESIGN: Cross-sectional study. SETTING: Rehabilitation Unit in a hospital. PARTICIPANTS: Ninety-nine patients with CLBP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional interference was assessed using PPIQ. The following data were also collected: sociodemographic data; pain intensity (Numeric Pain Rating Scale [NPRS]); physical functioning (30-s arm curl, 30-s chair stand [30CST], and timed Up and Go [TUG] tests), fitness (International Physical Activity Questionnaire); quality of life (Short-Form 12 Health Survey version 1 [SF-12v1]); sleep quality (Spanish-validated 12-item Medical Outcomes Study Sleep scale [12-MOS Sleep]); anxiety and depression (Hospital Anxiety and Depression Scale [HADS]); and social support (Duke-UNK Functional Social Support Questionnaire). Internal consistency was analyzed using Cronbach's alpha, structural validity using exploratory factor analysis (EFA), and discriminant and convergent validity using bivariate analysis. RESULTS: Ninety-nine patients with CLBP were included (age [mean ± SD]: 54.37±12.44 y); women, 67.7%). The EFA extracted 2 factors: "physical function and "social and sleep," which explained 57.75% of the variance. Excellent internal consistency was observed for the overall PPIQ score (Cronbach's α=0.866). Convergent validity was observed between the PPIQ and other functional measures (ρ: 0.52 and -0.47 for the TUG and 30CST, respectively; P<.001) and with the following variables: physical and mental component summaries of the SF-12v1 (ρ: -0. 55 and -0.52, respectively (P<.001); anxiety and depression of the HADS (ρ: 0.47 and 0.59, respectively (P<.001); NPRS (ρ: 0.45; P<.001); and index 9 of the 12-MOS Sleep scale (r: 0.49; P<.001). CONCLUSIONS: The PPIQ is a valid instrument with good psychometric properties for measuring functional interference in people with CLBP. This questionnaire appears to be a feasible alternative when language or communication barriers exist in CLBP population.

7.
BMC Nephrol ; 25(1): 24, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238661

RESUMO

This narrative review highlights strategies proposed by the Mexican Group of Experts on Arterial Hypertension endorsed to prevent, diagnose, and treat chronic kidney disease (CKD) related to systemic arterial hypertension (SAH). Given the growing prevalence of CKD in Mexico and Latin America caused by SAH, there is a need for context-specific approaches to address the effects of SAH, given the diverse population and unique challenges faced by the region. This narrative review provides clinical strategies for healthcare providers on preventing, diagnosing, and treating kidney disease related to SAH, focusing on primary prevention, early detection, evidence-based diagnostic approaches, and selecting pharmacological treatments. Key-strategies are focused on six fundamental areas: 1) Strategies to mitigate kidney disease in SAH, 2) early detection of CKD in SAH, 3) diagnosis and monitoring of SAH, 4) blood pressure targets in patients living with CKD, 5) hypertensive treatment in patients with CKD and 6) diuretics and Non-Steroidal Mineralocorticoid Receptor Inhibitors in Patients with CKD. This review aims to provide relevant strategies for the Mexican and Latin American clinical context, highlight the importance of a multidisciplinary approach to managing SAH, and the role of community-based programs in improving the quality of life for affected individuals. This position paper seeks to contribute to reducing the burden of SAH-related CKD and its complications in Mexico and Latin America.


Assuntos
Hipertensão , Insuficiência Renal Crônica , Humanos , México/epidemiologia , Qualidade de Vida , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Pressão Sanguínea
8.
Proc Natl Acad Sci U S A ; 118(33)2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34341069

RESUMO

Cueva de Ardales in Málaga, Spain, is one of the richest and best-preserved Paleolithic painted caves of southwestern Europe, containing over a thousand graphic representations. Here, we study the red pigment in panel II.A.3 of "Sala de las Estrellas," dated by U-Th to the Middle Paleolithic, to determine its composition, verify its anthropogenic nature, infer the associated behaviors, and discuss their implications. Using optical microscopy, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy, micro-Raman spectroscopy, and X-ray diffraction, we analyzed a set of samples from the panel and compared them to natural coloring materials collected from the floor and walls of the cave. The conspicuously different texture and composition of the geological samples indicates that the pigments used in the paintings do not come from the outcrops of colorant material known in the cave. We confirm that the paintings are not the result of natural processes and show that the composition of the paint is consistent with the artistic activity being recurrent. Our results strengthen the hypothesis that Neanderthals symbolically used these paintings and the large stalagmitic dome harboring them over an extended time span.

9.
Sensors (Basel) ; 24(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38400381

RESUMO

(1) Background: Leg length discrepancy (LLD), regardless of its origin, is a very common pathology that can contribute to low back pain. Various authors have pointed out its relationship with the lack of activation of both the gluteus medius (GM) and the ipsilateral erector spinae (ES). The purpose of this study was to identify the activation of the ES and GM with different simulated LLDs, correlating this activation with LBP. In turn, we evaluated whether ES and GM activity has an effect on jumping ability using a CMJ test. (2) Method: A sample of healthy subjects was selected to whom an artificial LLD was applied using 0.5, 1, and 1.5 cm insoles. These three heights were measured using EMG while the subjects walked and performed a counter movement jump (CMJ). The measurements of the insole heights were carried out in random order using a Latin square. Muscle activation patterns were recorded for 30 s at each of the insole heights while the patients walked at 5.7 km/h and they were compared with the maximum voluntary contraction (MVC), both on the ipsilateral and contralateral sides. These muscles were then measured under the same circumstances during the performance of the CMJ. (3) Results: We found statistically significant differences in the flight heights in both the CMJ and DJ. In the comparison, significant differences were found in the flight heights of the CMJ and the DJ using the 5 mm insoles, and in the case of the DJ, also without insoles, with respect to the MVC. We found statistically significant differences in the activation of the GM with the differences in insoles, but not in the activation of the Es in relation to the different insole heights. (4) Conclusions: Insoles of different heights caused activation differences in the medius on the side where the insoles were placed. We can relate this difference in activation to LBP. In relation to the ES, no significant differences were found in the activation of the ipsilateral side of the insole.


Assuntos
Ataxia Cerebelar , Humanos , Eletromiografia , Músculo Esquelético/fisiologia , Coxa da Perna , Nádegas
10.
Alzheimers Dement ; 20(7): 5009-5026, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38801124

RESUMO

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.


Assuntos
Demência , Humanos , Demência/terapia , Demência/diagnóstico , Demência/genética , Demência/epidemiologia , América Latina/epidemiologia , México/epidemiologia , Doença de Alzheimer/terapia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Pesquisa Biomédica , Congressos como Assunto
11.
Telemed J E Health ; 30(5): 1436-1442, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38215269

RESUMO

Background: Growth of international travel to malarial areas over the last decades has contributed to more travelers taking malaria prophylaxis. Travel-related symptoms may be wrongly attributed to malaria prophylaxis and hinder compliance. Here, we aimed to assess the frequency of real-time reporting of symptoms by travelers following malaria prophylaxis using a smartphone app. Method: Adult international travelers included in this single-center study (Barcelona, Spain) used the smartphone Trip Doctor® app developed by our group for real-time tracking of symptoms and adherence to prophylaxis. Results: Six hundred four (n = 604) international travelers were included in the study; 74.3% (449) used the app daily, and for one-quarter of travelers, malaria prophylaxis was prescribed. Participants from the prophylaxis group traveled more to Africa (86.7% vs. 4.3%; p < 0.01) and to high travel medical risk countries (60.8% vs. 18%; p < 0.01) and reported more immunosuppression (30.8% vs. 23.1% p < 0.01). Regarding symptoms, no significant intergroup differences were observed, and no relationship was found between the total number of malarial pills taken and reported symptoms. Conclusions: In our cohort, the number of symptoms due to malaria prophylaxis was not significantly higher than in participants for whom prophylaxis was not prescribed, and the overall proportion of symptoms is higher compared with other studies.


Assuntos
Antimaláricos , Malária , Aplicativos Móveis , Smartphone , Humanos , Malária/prevenção & controle , Feminino , Masculino , Antimaláricos/efeitos adversos , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Adulto , Pessoa de Meia-Idade , Espanha , Viagem , Adesão à Medicação/estatística & dados numéricos , Adulto Jovem
12.
Aten Primaria ; 56(8): 102930, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608330

RESUMO

OBJECTIVE: To determine the prevalence and related factors of diagnosed osteoarthrosis (DO) and undiagnosed osteoarthrosis (UO) in the general Spanish adult population. SETTING: Cross-sectional study with data from the Spanish National Health Survey 2017. PARTICIPANTS: N=23,089 adults. Three groups of people were defined: DO, UO, and no osteoarthrosis (NO). MAIN MEASUREMENTS: Sociodemographic information, lifestyle (tobacco, alcohol, physical activity, body mass index) and health factors (intensity of pain, pain drug consumption, mental health, self-perceived health status, pain involvement in daily living) were collected. Descriptive and bivariate analyses were performed, and a multinomial logistic regression model for the factors associated with each group. RESULTS: The prevalence of DO was 22.4% (95%CI=21.8;22.9) and 0.9% (95%CI=0.8;1) of UO. With respect to NO, risk factors for DO and UO included higher pain levels and pain drug consumption. Better self-perceived health status was inversely related with both. More pain involvement in daily living was associated with increased risk of DO, but reduced risk of UO. CONCLUSIONS: The prevalence of DO and UO was similar to that reported in Europe, but slightly higher than in low/middle-income countries. It was more prevalent in females, older people, people with worse perceived health status and worse mental health. Higher pain levels and pain drug consumption were risk factors for DO and UO. Better self-perceived health status was protective. Pain involvement in daily living was a risk factor for DO, but protective for UO. Different public health strategies should be considered in view of this.

13.
N Engl J Med ; 383(19): 1827-1837, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32459919

RESUMO

BACKGROUND: Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS: We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS: In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS: In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Adulto , Idoso , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/efeitos adversos , Betacoronavirus , COVID-19 , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Esquema de Medicação , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , SARS-CoV-2 , Resultado do Tratamento , Tratamento Farmacológico da COVID-19
14.
BMC Biotechnol ; 23(1): 18, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37415113

RESUMO

Plastic pollution is a major global concern to the health and wellbeing of all terrestrial and marine life. However, no sustainable method for waste management is currently viable. This study addresses the optimisation of microbial enzymatic polyethylene oxidation through rational engineering of laccases with carbohydrate-binding module (CBM) domains. An explorative bioinformatic approach was taken for high-throughput screening of candidate laccases and CBM domains, representing an exemplar workflow for future engineering research. Molecular docking simulated polyethylene binding whilst a deep-learning algorithm predicted catalytic activity. Protein properties were examined to interpret the mechanisms behind laccase-polyethylene binding. The incorporation of flexible GGGGS(x3) hinges were found to improve putative polyethylene binding of laccases. Whilst CBM1 family domains were predicted to bind polyethylene, they were suggested to detriment laccase-polyethylene associations. In contrast, CBM2 domains reported improved polyethylene binding and may thus optimise laccase oxidation. Interactions between CBM domains, linkers, and polyethylene hydrocarbons were heavily reliant on hydrophobicity. Preliminary polyethylene oxidation is considered a necessity for consequent microbial uptake and assimilation. However, slow oxidation and depolymerisation rates inhibit the large-scale industrial implementation of bioremediation within waste management systems. The optimised polyethylene oxidation of CBM2-engineered laccases represents a significant advancement towards a sustainable method of complete plastic breakdown. Results of this study offer a rapid, accessible workflow for further research into exoenzyme optimisation whilst elucidating mechanisms behind the laccase-polyethylene interaction.


Assuntos
Lacase , Polietileno , Lacase/química , Polietileno/metabolismo , Simulação de Acoplamento Molecular , Oxirredução , Carboidratos
15.
Am J Gastroenterol ; 118(7): 1237-1247, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36716287

RESUMO

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/tratamento farmacológico , Resultado do Tratamento , Indução de Remissão , Estudos Retrospectivos
16.
Respir Res ; 24(1): 26, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694181

RESUMO

BACKGROUND: Severe bronchiolitis is often associated with subsequent respiratory morbidity, mainly recurrent wheezing and asthma. However, the underlying immune mechanisms remain unclear. The main goal of this study was to investigate the association of nasal detection of periostin and thymic stromal lymphopoietin (TSLP) during severe bronchiolitis with the development of asthma at 4 years of age. METHODS: Observational, longitudinal, post-bronchiolitis, hospital-based, follow-up study. Children hospitalized for bronchiolitis between October/2013 and July/2017, currently aged 4 years, included in a previous study to investigate the nasal airway secretion of TSLP and periostin during bronchiolitis, were included. Parents were contacted by telephone, and were invited to a clinical interview based on a structured questionnaire to obtain information on the respiratory evolution. The ISAAC questionnaire for asthma symptoms for 6-7-year-old children, was also employed. RESULTS: A total of 248 children were included (median age 4.4 years). The mean age at admission for bronchiolitis was 3.1 (IQR: 1.5-6.5) months. Overall, 21% had ever been diagnosed with asthma and 37% had wheezed in the last 12 months. Measurable nasal TSLP was detected at admission in 27(11%) cases and periostin in 157(63%). The detection of nasal TSLP was associated with the subsequent prescription of maintenance asthma treatment (p = 0.04), montelukast (p = 0.01), and the combination montelukast/inhaled glucocorticosteroids (p = 0.03). Admissions for asthma tended to be more frequent in children with TSLP detection (p = 0.07). In the multivariate analysis, adjusting for potential confounders, the detection of TSLP remained independently associated with chronic asthma treatment prescription (aOR:2.724; CI 1.051-7.063, p:0.04) and with current asthma (aOR:3.41; CI 1.20-9.66, p:0.02). Nasal detection of periostin was associated with lower frequency of ever use of short-acting beta2-agonists (SABA) (p = 0.04), lower prevalence of current asthma (p = 0.02), less prescription of maintenance asthma treatment in the past 12 months (p = 0.02, respectively). In the multivariate analysis, periostin was associated with lower risk of asthma at 4 years, independently of the atopic status (aOR:0.511 CI 95% 0.284-0.918, p:0.025). CONCLUSIONS: Our results show a positive correlation between nasal TSLP detection in severe bronchiolitis and the presence of current asthma, prescription of asthma maintenance treatment and respiratory admissions up to the age of 4 years. By contrast, we found a protective association between nasal periostin detection and current asthma at 4 years, ever diagnosis of asthma, maintenance asthma treatment prescription, and respiratory admissions.


Assuntos
Asma , Bronquiolite , Infecções por Vírus Respiratório Sincicial , Criança , Pré-Escolar , Humanos , Lactente , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Asma/imunologia , Bronquiolite/complicações , Bronquiolite/diagnóstico , Bronquiolite/epidemiologia , Bronquiolite/imunologia , Citocinas , Seguimentos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Linfopoietina do Estroma do Timo
17.
Pediatr Res ; 94(3): 1180-1188, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37069223

RESUMO

BACKGROUND: Small for gestational age (SGA) perform a postnatal catch-up growth to recover their genetic trajectory. We studied the postnatal catch-up growth pattern of fetuses born with an appropriate-for-gestational-age (AGA) weight but with fetal growth deceleration (FGD) to explore whether they catch up. METHODS: Nine hundred and sixty-six newborns at Villalba University General Hospital (HUGV), were followed from 34 to 37 weeks to birth. Z-scores, adjusted for sex and age, of weight, length, and BMI at 3, 6, 9, and 12 months were calculated. We define catch-up as an increase in z-score greater than 0.67 SD in the growth curves. RESULTS: AGA FGD had lower mean weight and length than AGA non-FGD at all time points; BMI was lower until 3 months. AGA FGD had a lower weight, length, and BMI z-score (until 9, 6 months, and at birth, respectively) than AGA non-FGD. AGA FGD newborns had a significantly increased likelihood of weight catch-up at 3 months (OR 1.79; 95% CI: 1.16, 2.78; p = 0.009) and BMI in all investigated periods (OR 1.90; 95% CI 1.30, 2.78; p < 0.001 at 3 months), compared to AGA non-FGD newborns. CONCLUSIONS: AGA FGD newborns perform catch-up growth, especially in weight and BMI, in the first year of life, compared to AGA non-FGD. IMPACT: Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a lower weight and height, during the first year of life, compared to AGA non-FGD. Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a higher likelihood of weight catch-up in the first 3 months of life and of BMI in the first year compared to AGA non-FGD. AGA FGD experienced early weight and BMI catch-up, especially in the first 3 months of life, like SGA. This finding should be considered in the future follow-up.


Assuntos
Estatura , Peso Fetal , Gravidez , Feminino , Recém-Nascido , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Retardo do Crescimento Fetal , Idade Gestacional
18.
Crit Rev Food Sci Nutr ; : 1-10, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37449467

RESUMO

A systematic review with meta-analysis was conducted to analyze the effect of carbohydrate (CHO) intake during exercise and some variables that could moderate this effect on endurance performance. We included 136 studies examining the effect of CHO ingestion during endurance exercise in the meta-analysis. The overall effect on performance showed a significant increase after CHO intake compared to the placebo/control groups. A larger effect of CHO consumption is observed in time to exhaustion than in time trials performance test. Moreover, the effectiveness of CHO supplementation was greater the longer the duration of the events. Also, there seems to be a higher effect of CHO intake in lower trained than in higher trained participants. In contrast, the magnitude of performance change of CHO intake is not affected by the dosage, ergometer used, the type of intake of the CHO ingestion and the type of CHO. In addition, a lower rate of perceived exertion and higher power and heart rate are significantly associated with the ingestion of CHO during endurance exercise. These results reinforce that acute CHO feeding is an effective strategy for improving endurance performance, especially, in less trained subjects participating in time to exhaustion tests of longer durations.

19.
Eur J Nutr ; 62(8): 3349-3359, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37624376

RESUMO

PURPOSE: Mycoprotein is a relatively novel food source produced from the biomass of Fusarium venenatum. It has previously been shown to improve CVD risk markers in intervention trials when it is compared against total meat. It has not hitherto been assessed specifically for benefits relative to red and processed meat. METHODS: We leveraged samples from Mycomeat, an investigator-blind randomised crossover controlled trial in metabolically healthy male adults (n = 20), randomised to consume 240 g/day of red and processed meat for 14 days followed by mycoprotein, or vice versa. Blood biochemical indices were a priori defined secondary endpoints. RESULTS: Mycoprotein consumption led to a 6.74% reduction in total cholesterol (P = 0.02) and 12.3% reduction in LDL cholesterol (P = 0.02) from baseline values. Change in fasted triglycerides was not significantly different between diets (+ 0.19 ± 0.11 mmol/l with mycoprotein, P = 0.09). There was a small but significant reduction in waist circumference for mycoprotein relative to meat (- 0.95 ± 0.42 cm, P = 0.04). Following the mycoprotein diet, mean systolic (- 2.41 ± 1.89 mmHg, P = 0.23) and diastolic blood pressure (- 0.80 ± 1.23 mmHg, P = 0.43) were reduced from baseline. There were no statistically significant effects of the intervention on urinary sodium, nitrite or TMAO; while urinary potassium (+ 126.12 ± 50.30 mmol/l, P = 0.02) and nitrate (+ 2.12 ± 0.90 mmol/l, P = 0.04) were both significantly higher with mycoprotein relative to meat. The study population comprised metabolically healthy adults, therefore, changes in plasma lipids had little effect on cardiovascular risk scores (- 0.34% FRS for mycoprotein P = 0.24). CONCLUSIONS: These results confirm potential cardiovascular benefits when displacing red and processed meat with mycoprotein in the diet. Longer trials in higher risk study populations are needed to fully elucidate suggested benefits for blood pressure and body composition. CLINICALTRIALS: gov Identifier: NCT03944421.


Assuntos
Doenças Cardiovasculares , Carne Vermelha , Adulto , Humanos , Masculino , Biomarcadores , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol , Fatores de Risco de Doenças Cardíacas , Carne , Fatores de Risco , Estudos Cross-Over
20.
Eur J Nutr ; 62(3): 1479-1492, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36651990

RESUMO

PURPOSE: The high-meat, low-fibre Western diet is strongly associated with colorectal cancer risk. Mycoprotein, produced from Fusarium venanatum, has been sold as a high-fibre alternative to meat for decades. Hitherto, the effects of mycoprotein in the human bowel have not been well considered. Here, we explored the effects of replacing a high red and processed meat intake with mycoprotein on markers of intestinal genotoxicity and gut health. METHODS: Mycomeat (clinicaltrials.gov NCT03944421) was an investigator-blind, randomised, crossover dietary intervention trial. Twenty healthy male adults were randomised to consume 240 g day-1 red and processed meat for 2 weeks, with crossover to 2 weeks 240 g day-1 mycoprotein, separated by a 4-week washout period. Primary end points were faecal genotoxicity and genotoxins, while secondary end points comprised changes in gut microbiome composition and activity. RESULTS: The meat diet increased faecal genotoxicity and nitroso compound excretion, whereas the weight-matched consumption of mycoprotein decreased faecal genotoxicity and nitroso compounds. In addition, meat intake increased the abundance of Oscillobacter and Alistipes, whereas mycoprotein consumption increased Lactobacilli, Roseburia and Akkermansia, as well as the excretion of short chain fatty acids. CONCLUSION: Replacing red and processed meat with the Fusarium-based meat alternative, mycoprotein, significantly reduces faecal genotoxicity and genotoxin excretion and increases the abundance of microbial genera with putative health benefits in the gut. This work demonstrates that mycoprotein may be a beneficial alternative to meat within the context of gut health and colorectal cancer prevention.


Assuntos
Neoplasias Colorretais , Carne , Adulto , Masculino , Humanos , Carne/efeitos adversos , Dieta , Ácidos Graxos Voláteis , Dano ao DNA , Compostos Nitrosos
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