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1.
J Transl Med ; 22(1): 424, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704581

RESUMO

BACKGROUND: The measurement of the skin carotenoids using the Veggie Meter® has emerged as a rapid objective method for assessing fruit and vegetable intake, highly recommended by the Mediterranean Diet (MD), which represents one of the healthiest dietary patterns, worldwide. This study aimed to examine differences in skin carotenoid content and degree of adherence to the MD pattern between two adult populations from Southern Italy and the Dominican Republic. METHODS: This cross-sectional study enrolled a total of 995 adults, 601 subjects from Italy and 394 from the Dominican Republic. All participants underwent anthropometric measurements and skin carotenoid assessment by Veggie Meter®. Adherence to the MD and lifestyle were evaluated using the Mediterranean Diet Adherence Screener (MEDAS) and the Mediterranean Lifestyle Index (MEDLIFE) questionnaires. Correlations between the skin carotenoid and MEDAS score were estimated using Pearson's correlation coefficient. Multiple linear regression models were created to determine variables that affect skin carotenoid score for both populations. RESULTS: Mean total skin carotenoids were higher in the Italian compared to the Dominican Republic population (342.4 ± 92.4 vs 282.9 ± 90.3; p < 0.005) regardless of sex (women: 318.5 ± 88.9 vs 277.3 ± 91.9, p < 0.005 and men: 371.7 ± 88.3 vs 289.5 ± 88.1, p < 0.005), and remaining statistically significant after age-adjustment of the Dominican Republic sample. Using the MEDAS questionnaire, we found a higher MD adherence score in the Italian than in the Dominican Republic population also after age-adjusting data (7.8 ± 2.1 vs 6.2 ± 3.7; p < 0.005) and even when categorized by sex (Italian vs age-adjusted Dominican Republic women: 7.9 ± 2.1 vs 6.3 ± 2.6; Italian vs age-adjusted Dominican Republic men: 7.7 ± 2.2 vs 6.0 ± 4.7; p < 0.005). Using the MEDLIFE test, total Italians presented a lower score with respect to the age-adjusted Dominican Republic population (3.2 ± 1.2 vs 3.4 ± 1.4; p < 0.05). In multiple regression analysis, skin carotenoids were associated with sex and negatively associated with BMI in the Italian population (sex: ß: 54.95; 95% CI: 40.11, 69.78; p < 0.0001; BMI: ß: - 1.60; 95% CI: - 2.98,0.86; p = 0.03), while they resulted associated with age and sex in the Dominican Republic population (age: ß: 2.76; 95% CI: 1.92, 3.56; p < 0.001; sex: ß: 23.29; 95% CI: 5.93, 40.64; p = 0.009). Interestingly, skin carotenoids were positively correlated with MEDAS score in both populations (Italy: r = 0.03, p < 0.0001, Dominican Republic: r = 0.16, p = 0.002). CONCLUSIONS: This study provides the assessment of the adherence to the MD and skin carotenoid content in adults living in Southern Italy and the Dominican Republic, showing a higher MD adherence score and a skin carotenoid content in inhabitants from the Mediterranean region. Our findings highlight the need to globally encourage fruit and vegetable intake, particularly in non-Mediterranean area.


Assuntos
Carotenoides , Dieta Mediterrânea , Pele , Humanos , Itália , República Dominicana , Carotenoides/análise , Carotenoides/metabolismo , Feminino , Masculino , Adulto , Pele/metabolismo , Pessoa de Meia-Idade , Estudos Transversais , Cooperação do Paciente/estatística & dados numéricos , Inquéritos e Questionários
2.
Cancer Lett ; 591: 216879, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636895

RESUMO

Galectin-3 (Gal-3) is a multifunctional protein that plays a pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although the involvement of Gal-3 in tumour progression, resistance to treatment and immunosuppression has long been studied in different cancer types, mainly outside the central nervous system, its elevated expression in myeloid and glial cells underscores its profound impact on the brain's immune response. In this context, microglia and infiltrating macrophages, the predominant non-cancerous cells within the tumour microenvironment, play critical roles in establishing an immunosuppressive milieu in diverse brain tumours. Through the utilisation of primary cell cultures and immortalised microglial cell lines, we have elucidated the central role of Gal-3 in promoting cancer cell migration, invasion, and an immunosuppressive microglial phenotypic activation. Furthermore, employing two distinct in vivo models encompassing primary (glioblastoma) and secondary brain tumours (breast cancer brain metastasis), our histological and transcriptomic analysis show that Gal-3 depletion triggers a robust pro-inflammatory response within the tumour microenvironment, notably based on interferon-related pathways. Interestingly, this response is prominently observed in tumour-associated microglia and macrophages (TAMs), resulting in the suppression of cancer cells growth.


Assuntos
Neoplasias Encefálicas , Movimento Celular , Proliferação de Células , Galectina 3 , Glioblastoma , Microglia , Microambiente Tumoral , Microglia/metabolismo , Microglia/patologia , Galectina 3/metabolismo , Galectina 3/genética , Humanos , Animais , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/genética , Glioblastoma/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Linhagem Celular Tumoral , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Macrófagos/metabolismo , Macrófagos/imunologia , Invasividade Neoplásica , Proteínas Sanguíneas/metabolismo , Galectinas/metabolismo , Galectinas/genética , Transdução de Sinais , Camundongos , Regulação Neoplásica da Expressão Gênica
3.
Neuropathol Appl Neurobiol ; 50(1): e12962, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38343067

RESUMO

AIMS: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. METHODS: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. RESULTS: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD. CONCLUSION: These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.


Assuntos
Doenças Inflamatórias Intestinais , Doença de Parkinson , Humanos , Ratos , Animais , alfa-Sinucleína/metabolismo , Doença de Parkinson/patologia , Encéfalo/patologia , Inflamação/patologia , Neurônios Dopaminérgicos/metabolismo , Doenças Inflamatórias Intestinais/patologia
4.
PLoS Negl Trop Dis ; 18(1): e0011889, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38190394

RESUMO

BACKGROUND: Currently, vaccination of livestock with attenuated strains of Brucella remains an essential measure for controlling brucellosis, although these vaccines may be dangerous to humans. The aim of this study was to review the risk posed to humans by occupational exposure to vaccine strains and the measures that should be implemented to minimize this risk. METHODS: This article reviewed the scientific literature indexed in PubMed up to September 30, 2023, following "the PRISMA guidelines". Special emphasis was placed on the vaccine strain used and the route of exposure. Non-occupational exposure to vaccine strains, intentional human inoculation, publications on exposure to wild strains, and secondary scientific sources were excluded from the study. RESULTS: Nineteen primary reports were found and classified in three subgroups: safety accidents in vaccine factories that led to an outbreak (n = 2), survellaince studies on vaccine manufacturing workers with a serologic diagnosis of Brucella infection (n = 3), and publications of infection by vaccine strains during their administration, including case reports, records of occupational accidents and investigations of outbreaks in vaccination campaigns (n = 14). Although accidental exposure during vaccine manufacturing were uncommon, they could provoke large outbreaks through airborne spread with risk of spread to the neighboring population. Besides, despite strict protection measures, a percentage of vaccine manufacturing workers developed positive Brucella serology without clinical infection. The most frequent type of exposure with symptomatic infection was needle injury during vaccine administration. Prolonged contact with the pathogen, lack of information and a low adherence to personal protective equipment (PPE) use in the work environment were commonly associated with infection. CONCLUSIONS: Brucella vaccines pose occupational risk of contagion to humans from their production to their administration to livestock, although morbidity is low and deaths were not reported. Recommended protective measures and active surveillance of exposed workers appeared to reduce this risk. It would be advisable to carry out observational studies and/or systematic registries using solid diagnostic criteria.


Assuntos
Vacina contra Brucelose , Brucella , Brucelose , Exposição Ocupacional , Animais , Humanos , Brucelose/epidemiologia , Brucelose/prevenção & controle , Vacinação , Gado , Vacinas Atenuadas
5.
Oper Neurosurg (Hagerstown) ; 26(2): 149-155, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37831977

RESUMO

BACKGROUND AND OBJECTIVES: Lumbosacral plexus schwannomas (LSPSs) are benign, slow-growing tumors that arise from the myelin sheath of the lumbar or sacral plexus nerves. Surgery is the treatment of choice for symptomatic LSPSs. Conventional retroperitoneal or transabdominal approaches provide wide exposure of the lesion but are often associated with complications in the abdominal wall, lumbar or sacral plexus, ureter, and intraperitoneal organs. Advances in technology and minimally invasive (MIS) techniques have provided alternative approaches with reliable efficacy compared with traditional open surgery. We describe 3 MIS approaches using tubular retractor systems according to the lesion level. METHODS: This was a multicenter, retrospective observational cohort study to evaluate the use of MIS tubular approaches for surgical resection of LSPSs. We included 23 lumbar and upper sacral plexus schwannomas. Clinical presentation, spinal level, surgical duration, degree of resection, days of hospitalization, pathological anatomy of the tumor, approach-related surgical difficulties, and outcomes were collected. RESULTS: The posterior oblique approach was used in 43.5% of the cases, the transpsoas approach in 39.1%, and the transiliac in 17.4%. The mean operative time was 3.3 hours, and the mean hospitalization was 2.5 days. All tumors were WHO grade 1 schwannoma. Postoperative MRI confirms gross total resection in 91.3% of the patients. No patient requires instrumentation. The pros and cons of each approach were summarized. CONCLUSION: The MIS approaches adapted to the lumbar level may improve surgeons' comfort allowing a safe resection of retroperitoneal LSPS.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos , Neurilemoma , Humanos , Estudos Retrospectivos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Vértebras Lombares/cirurgia , Plexo Lombossacral/cirurgia , Plexo Lombossacral/patologia , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Neurilemoma/patologia
6.
Sensors (Basel) ; 23(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38067707

RESUMO

The worldwide popularisation of running as a sport and recreational practice has led to a high rate of musculoskeletal injuries, usually caused by a lack of knowledge about the most suitable running technique for each runner. This running technique is determined by a runner's anthropometric body characteristics, dexterity and skill. Therefore, this study aims to develop a motion capture-based running analysis test on a treadmill called KeepRunning to obtain running patterns rapidly, which will aid coaches and clinicians in assessing changes in running technique considering changes in the study variables. Therefore, a review and proposal of the most representative events and variables of analysis in running was conducted to develop the KeepRunning test. Likewise, the minimal detectable change (MDC) in these variables was obtained using test-retest reliability to demonstrate the reproducibility and viability of the test, as well as the use of MDC as a threshold for future assessments. The test-retest consisted of 32 healthy volunteer athletes with a running training routine of at least 15 km per week repeating the test twice. In each test, clusters of markers were placed on the runners' body segments using elastic bands and the volunteers' movements were captured while running on a treadmill. In this study, reproducibility was defined by the intraclass correlation coefficient (ICC) and MDC, obtaining a mean value of ICC = 0.94 ± 0.05 for all variables and MDC = 2.73 ± 1.16° for the angular kinematic variables. The results obtained in the test-retest reveal that the reproducibility of the test was similar or better than that found in the literature. KeepRunning is a running analysis test that provides data from the involved body segments rapidly and easily interpretable. This data allows clinicians and coaches to objectively provide indications for runners to improve their running technique and avoid possible injury. The proposed test can be used in the future with inertial motion capture and other wearable technologies.


Assuntos
Dispositivos Eletrônicos Vestíveis , Humanos , Reprodutibilidade dos Testes , Tempo de Protrombina , Fenômenos Biomecânicos
7.
Front Microbiol ; 14: 1221682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601355

RESUMO

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.

8.
PDA J Pharm Sci Technol ; 77(5): 376-401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37321861

RESUMO

With machine learning (ML), we see the potential to better harness the intelligence and decision-making abilities of human inspectors performing manual visual inspection (MVI) and apply this to automated visual inspection (AVI) with the inherent improvements in throughput and consistency. This article is intended to capture current experience with this new technology and provides points to consider for successful application to AVI of injectable drug products. The technology is available today for such AVI applications. Machine vision companies have integrated ML as an additional visual inspection tool with minimal upgrades to existing hardware. Studies have demonstrated superior results in defect detection and reduction in false rejects, when compared with conventional inspection tools. ML implementation does not require modifications to current AVI qualification strategies. The utilization of this technology for AVI will accelerate recipe development by use of faster computers rather than by direct human configuration and coding of vision tools. By freezing the model developed with artificial intelligence tools and subjecting it to current validation strategies, assurance of reliable performance in the production environment can be achieved.


Assuntos
Inteligência Artificial , Aprendizado de Máquina , Humanos , Tecnologia , Injeções
9.
J Vis Exp ; (196)2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37335107

RESUMO

One of the biggest challenges in developing effective therapies against glioblastoma is overcoming the strong immune suppression within the tumor microenvironment. Immunotherapy has emerged as an effective strategy to turn the immune system response against tumor cells. Glioma-associated macrophages and microglia (GAMs) are major drivers of such anti-inflammatory scenarios. Therefore, enhancing the anti-cancerous response in GAMs may represent a potential co-adjuvant therapy to treat glioblastoma patients. In that vein, fungal ß-glucan molecules have long been known as potent immune modulators. Their ability to stimulate the innate immune activity and improve treatment response has been described. Those modulating features are partly attributed to their ability to bind to pattern recognition receptors, which, interestingly, are greatly expressed in GAMs. Thus, this work is focused on the isolation, purification, and subsequent use of fungal ß-glucans to enhance the tumoricidal response of microglia against glioblastoma cells. The mouse glioblastoma (GL261) and microglia (BV-2) cell lines are used to test the immunomodulatory properties of four different fungal ß-glucans extracted from mushrooms heavily used in the current biopharmaceutical industry: Pleurotus ostreatus, Pleurotus djamor, Hericium erinaceus, and Ganoderma lucidum. To test these compounds, co-stimulation assays were performed to measure the effect of a pre-activated microglia-conditioned medium on the proliferation and apoptosis activation in glioblastoma cells.


Assuntos
Glioblastoma , Glioma , beta-Glucanas , Animais , Camundongos , Glioblastoma/patologia , beta-Glucanas/farmacologia , beta-Glucanas/metabolismo , Macrófagos/metabolismo , Glioma/patologia , Microglia/metabolismo , Imunoterapia , Microambiente Tumoral
10.
Cureus ; 15(2): e34596, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36883081

RESUMO

A healthy 12-year-old presented with wheezing and progressive dyspnea over a 10-month period. He had several general physician consultations and emergency visits during this time and was treated as an asthma exacerbation with no clinical response. He was referred to the pediatric pulmonologist and a tracheal deviation in his previous two chest X-rays was noted, therefore further studies were performed. A severe extrinsic tracheal compression due to a mediastinal mass was documented. He was taken into surgery where a partial resection of the tumor was made. The biopsy of the tumor reported an inflammatory myofibroblastic tumor (IMT), a rare tumor with an atypical presentation, which made this case a diagnostic challenge.

12.
Bioorg Med Chem ; 71: 116946, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35939903

RESUMO

Naphthalene diimide (NDI) is a central scaffold that has been commonly used in the design of G-quadruplex (G4) ligands. Previous work revealed notable anticancer activity of a disubstituted N-methylpiperazine propyl NDI G4 ligand. Here, we explored structure-activity relationship studies around ligand bis-N,N-2,7-(3-(4-methylpiperazin-1-yl)propyl)-1,4,5,8-naphthalenetetracarboxylic diimide, maintaining the central NDI core whilst modifying the spacer and the nature of the cationic groups. We prepared new disubstituted NDI derivatives of the original compound and examined their in vitro antiproliferative and antiparasitic activity. Several N-methylpiperazine propyl NDIs showed sub-micromolar activity against Trypanosoma brucei and Leishmania major parasites with up to 30 fold selectivity versus MRC-5 cells. The best compound was a dimorpholino NDI with an IC50 of 0.17 µM against T.brucei and 40 fold selectivity versus MRC-5 cells. However, no clear correlation between G4 binding of the new NDI derivatives and antiproliferative or antiparasitic activity was observed, indicating that other mechanisms of action may be responsible for the observed biological activity.


Assuntos
Antiparasitários , Quadruplex G , Antiparasitários/química , Antiparasitários/farmacologia , Imidas/química , Imidas/farmacologia , Ligantes , Naftalenos , Relação Estrutura-Atividade
13.
Cell Death Dis ; 13(7): 628, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35859075

RESUMO

The advent of high-throughput single-cell transcriptomic analysis of microglia has revealed different phenotypes that are inherently associated with disease conditions. A common feature of some of these activated phenotypes is the upregulation of galectin-3. Representative examples of these phenotypes include disease-associated microglia (DAM) and white-associated microglia (WAM), whose role(s) in neuroprotection/neurotoxicity is a matter of high interest in the microglia community. In this review, we summarise the main findings that demonstrate the ability of galectin-3 to interact with key pattern recognition receptors, including, among others, TLR4 and TREM2 and the importance of galectin-3 in the regulation of microglia activation. Finally, we discuss increasing evidence supporting the involvement of this lectin in the main neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, and stroke.


Assuntos
Doença de Alzheimer , Doença de Parkinson , Doença de Alzheimer/genética , Galectina 3/genética , Humanos , Microglia
15.
Vet Sci ; 9(3)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35324844

RESUMO

The effect of Leishmania infantum soluble antigen (LSA) and recombinant Kinetoplastid Membrane Protein 11 (rKMP11) on the induction of ex vivo specific IFN-γ (n = 69) and antibody responses (n = 108) was determined in dogs. All dogs were tested for serological response to both antigens and divided into Group 1: healthy (Asturias, Spain, n = 26), Group 2: sick (n = 46), Group 3: healthy Ibizan hounds (Mallorca, Spain, n = 22) and Group 4: healthy (Bari, Italy, n = 14). Antibody levels were higher for LSA when compared to rKMP11 (p = 0.001). Ibizan hounds were all seronegative to rKMP11 and 18% were low seropositive to LSA. Sick dogs presented higher antibody response to both antigens compared to the rest of the groups (p < 0.0001). All groups showed higher IFN-γ levels after LSA compared to rKMP11 responses (p < 0.05). The highest response to LSA was found in Ibizan hounds (p < 0.05). IFN-γ to LSA and rKMP11 stimulation was observed in 34% and in 2.8% of the sick dogs, respectively. Here, we demonstrated that anti-rKMP11 antibodies are mainly present in dogs with moderate to severe disease. Furthermore, cellular immune response measured by specific ex vivo IFN-γ production was more intense to LSA than stimulated to rKMP11.

17.
Molecules ; 27(4)2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35208978

RESUMO

The effects of hydrostatic (HHP) and dynamic (HPH) high-pressure treatments on the activity of pectin methylesterase (PME) and polyphenol oxidase (PPO) as well as the physicochemical quality attributes of 'Ataulfo' mango nectar were assessed. HHP reduced PME relative activity by 28% at 100 MPa for 5 min but increased PPO activity almost five-fold. Contrarily, HPH did not affect PME activity, but PPO was effectively reduced to 10% of residual activity at 300 MPa and at three passes. Color parameters (CIEL*a*b*), °hue, and chroma were differently affected by each type of high-pressure processing technology. The viscosity and fluid behavior were not affected by HHP, however, HPH changed the apparent viscosity at low dynamic pressure levels (100 MPa with one and three passes). The viscosity decreased at high shear rates in nectar samples, showing a shear-thinning effect. The results highlight how different effects can be achieved with each high-pressure technology; thus, selecting the most appropriate system for processing and preserving liquid foods like fruit beverages is recommended.


Assuntos
Bebidas , Hidrolases de Éster Carboxílico/química , Frutas/enzimologia , Mangifera/enzimologia , Proteínas de Plantas/química , Pressão Hidrostática
18.
J Clin Invest ; 132(6)2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35113813

RESUMO

New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1-positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.


Assuntos
Antineoplásicos , Glioblastoma , Antineoplásicos/uso terapêutico , Arginina , Argininossuccinato Sintase/genética , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Humanos , Hidrolases , Microglia , Polietilenoglicóis
19.
Artigo em Espanhol | LILACS | ID: biblio-1388711

RESUMO

Resumen La embolia de líquido amniótico es una condición catastrófica propia del embarazo que ocurre típicamente durante el parto o justo posterior a este, cuyo sustrato fisiopatológico no ha sido aclarado por completo. Se ha estimado, según cifras de los Estados Unidos, que su incidencia rondaría 1 por cada 12.953 partos, y en el Reino Unido 1 por cada 50.000 partos; sin embargo, estas cifras pueden ser imprecisas debido a que no existen una referencia ni un consenso respecto a los criterios diagnósticos, además de que el cuadro clínico se puede confundir con otras emergencias obstétricas. Se presenta el caso de una paciente sin antecedentes mórbidos que presenta un cuadro de embolia de líquido amniótico no fatal, caracterizado por un estado fetal no tranquilizador durante la inducción del trabajo de parto, seguido de un paro cardiorrespiratorio durante la cesárea de urgencia y la rápida y catastrófica aparición de signos clínicos de una coagulopatía de consumo grave. Se describen además las complicaciones posoperatorias y su manejo, entre ellas un síndrome de Sheehan y la aparición de convulsiones tónico-clónicas generalizadas con alteración de neuroimágenes.


Abstract Amniotic fluid embolism is a catastrophic pregnancy condition that typically occurs during or inmediately after delivery, and whose pathophysiological background has not been fully clarified. According to US records the incidence of amniotic fluid embolism could been around 1 for every 12,953 births and in the United Kingdom 1 for every 50,000 births, however these numbers may be imprecise because there is no gold standard as well as no consensus regarding the diagnostic criteria, in addition that the clinical presentation can be misdiagnosis with other obstetric emergencies. We present the clinical case of a patient without a morbid history who presents with a non-fatal amniotic fluid embolism, characterized by an non-reassuring fetal status during labor induction, followed by cardiorespiratory arrest during emergency cesarean section and the rapid and catastrophic appearance of clinical signs of a severe consumptive coagulopathy. Postoperative complications and their management are also described, including Sheehans syndrome and the appearance of generalized tonic-clonic seizures with impaired neuroimaging.


Assuntos
Humanos , Feminino , Gravidez , Adulto , Embolia Amniótica/cirurgia , Parada Cardíaca/etiologia , Hipopituitarismo/etiologia , Cesárea , Reanimação Cardiopulmonar , Coagulação Intravascular Disseminada , Emergências , Parada Cardíaca/terapia , Hipopituitarismo/terapia
20.
Nutr Hosp ; 39(1): 223-229, 2022 Feb 09.
Artigo em Espanhol | MEDLINE | ID: mdl-34431302

RESUMO

INTRODUCTION: Aim: to present the results of the Spanish home enteral nutrition (HEN) registry of the NADYA-SENPE group for the years 2018 and 2019. Material and methods: from January 1, 2018 to December 31, 2019 the home enteral nutrition registry was recorded, and afterwards a further descriptive and analytical analysis was done. Results: in 2018, 4756 active patients were registered and the prevalence was 101.79 patients per one million inhabitants; in 2019 there were 4633 patients with a prevalence of 98.51 patients per one million inhabitants. They originated in 46 hospitals: 51.3 % were male, and median age was 71.0 years in both periods. The most frequent diagnosis was a neurological disorder that presents with aphagia or severe dysphagia - 58.7 % and 58.2 %, respectively. The main cause of episode termination was death. A total of 116 pediatric patients were registered in 2018 and 115 in 2019. Females represented 57.8 % and 59.1 %, respectively, in each of the periods. Median age at the beginning of HEN was 5 and 7 months. The most commonly recordered diagnostic group (42.2 % and 42.6 %) was included within the other pathologies group, followed by neurological disorders that present with aphagia or severe dysphagia in 41.4 % and 41.7 % of children. The route of administration was gastrostomy in 46.6 % and 46.1 %, respectively, in each of the periods. Conclusions: the NED registry of the NADYA-SENPE group continues to operate uninterruptedly since its inception. The number of registered patients and the number of participating hospitals remained stable in the last biennium analyzed.


INTRODUCCIÓN: Objetivo: exponer los resultados del registro de nutrición enteral domiciliaria (NED) de los años 2018 y 2019 del Grupo NADYA-SENPE. Material y métodos: se recopilaron los pacientes introducidos en el registro desde el 1 de enero al 31 de diciembre de 2018 y en las mismas fechas para 2019, procediendo al análisis descriptivo y analítico de los datos. Resultados: en el año 2018 se registraron 4756 pacientes activos con una tasa de prevalencia de 101,79 pacientes/millón de habitantes; en 2019 fueron 4633 con una tasa de prevalencia de 98,51 pacientes/millón de habitantes. Procedían de 46 hospitales. Fueron el 51,3 % los varones registrados y la edad mediana fue de 71,0 años en ambos periodos. El diagnóstico más frecuente fue el de enfermedad neurológica que cursa con afagia o disfagia severa (58,7 % y 58,2 %), respectivamente. La causa principal de finalización de los episodios fue el fallecimiento. Los pacientes pediátricos registrados fueron 116 en 2018 y 115 en 2019. Las niñas representaron el 57,8 % y 59,1 %, respectivamente, en cada uno de los periodos. La edad mediana de inicio de la NED fue de 5 y 7 meses. El grupo diagnóstico más registrado (42,2 % y 42,6 %) se englobó dentro del grupo de otras patologías, seguido de la enfermedad neurológica que cursa con afagia o disfagia severa de los niños (41,4 % y 41,7 %). Se alimentaban a través de gastrostomía el 46,6 % y 46,1 %, respectivamente, en cada uno de los periodos. Conclusiones: el registro de NED del grupo NADYA-SENPE sigue operativo de forma ininterrumpida desde sus inicios. El número de pacientes registrados y el de hospitales participantes permanece estable en el último bienio analizado.


Assuntos
Nutrição Enteral , Nutrição Parenteral no Domicílio , Idoso , Criança , Feminino , Gastrostomia , Humanos , Masculino , Sistema de Registros , Espanha/epidemiologia
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