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1.
EMBO J ; 41(22): e111952, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36314651

RESUMO

Aging is a major risk factor to develop neurodegenerative diseases and is associated with decreased buffering capacity of the proteostasis network. We investigated the significance of the unfolded protein response (UPR), a major signaling pathway activated to cope with endoplasmic reticulum (ER) stress, in the functional deterioration of the mammalian brain during aging. We report that genetic disruption of the ER stress sensor IRE1 accelerated age-related cognitive decline. In mouse models, overexpressing an active form of the UPR transcription factor XBP1 restored synaptic and cognitive function, in addition to reducing cell senescence. Proteomic profiling of hippocampal tissue showed that XBP1 expression significantly restore changes associated with aging, including factors involved in synaptic function and pathways linked to neurodegenerative diseases. The genes modified by XBP1 in the aged hippocampus where also altered. Collectively, our results demonstrate that strategies to manipulate the UPR in mammals may help sustain healthy brain aging.


Assuntos
Envelhecimento , Encéfalo , Proteínas Serina-Treonina Quinases , Resposta a Proteínas não Dobradas , Proteína 1 de Ligação a X-Box , Animais , Camundongos , Envelhecimento/genética , Encéfalo/metabolismo , Estresse do Retículo Endoplasmático/genética , Proteínas Serina-Treonina Quinases/genética , Proteômica , Transdução de Sinais/fisiologia , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
2.
Eur J Nucl Med Mol Imaging ; 51(5): 1395-1408, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38095674

RESUMO

PURPOSE: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as an additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLT nephrotoxicity. METHODS: A bifunctional cyclic peptide, melanocortin 1 ligand (MC1L), labeled with [203Pb]Pb-MC1L, was used for [212Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [212Pb]Pb-MC1L in a dose-escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. RESULTS: Biodistribution analysis identified [212Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [212Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [212Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. CONCLUSION: Urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.


Assuntos
Chumbo , Insuficiência Renal Crônica , Camundongos , Animais , Lipocalina-2/urina , Distribuição Tecidual , Detecção Precoce de Câncer , Biomarcadores , Creatinina
3.
BMC Cancer ; 24(1): 161, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302893

RESUMO

BACKGROUND: In 2020, the highest incidence and mortality from cervical cancer (CC) were detected in low and middle-income countries. CC remains a health problem for women living in them. In Mexico, CC ranks second in cancer incidence and mortality in women. The main characteristics of this population are low income, low educational level, and inadequate medical coverage. The present study characterized the Mexican population by CC, and the sociodemographic variables that impacted overall survival (OS) were identified. METHODS: A retrospective study that included a cohort of patients with a confirmed diagnosis of CC at the Instituto Nacional de Cancerologia between 2003 and 2016. Information was collected on sociodemographic variables related to the disease and OS. RESULTS: Four thousand six hundred thirty-one patients were included. The median age was 51 years, 78.5% were unemployed, 44.4% lived in a rural/suburban area, 50.8% had a partner when collecting this information, and 74.3% were classified as having low socioeconomic status. Age, living in a rural/suburban area, more advanced stages of the disease, and not receiving cancer treatment were associated with lower OS. CONCLUSION: CC continues to affect mainly women with minimal resources, low educational levels, and living in marginalized areas. These characteristics influence the OS. Prevention and timely detection programs, education, and training focused on this population and with broader coverage are required to identify patients with CC at earlier stages.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/diagnóstico , Estudos Retrospectivos , Pobreza , Escolaridade , Incidência
4.
Pediatr Nephrol ; 39(2): 569-577, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37552466

RESUMO

BACKGROUND: In patients requiring mechanical circulatory support (MCS), the incidence of acute kidney injury (AKI) is between 37 and 63%. In this study, we performed an exploratory analysis evaluating the relationship of multiple urine biomarkers with AKI development in pediatric MCS patients. METHODS: This is a single center retrospective study in a pediatric cohort receiving MCS from August 2014 to November 2020. We measured 14 urine biomarkers of kidney injury on day 1 following MCS initiation and analyzed their association with development of AKI in the first 7 days of MCS initiation. RESULTS: Sixty patients met inclusion criteria. Patients with AKI were more likely to be supported by venoarterial extracorporeal membrane oxygenation (65% vs. 8.3%, p < 0.001), compared to the no AKI group and less likely to have ventricular assist devices (10% vs. 50%, p < 0.001). There was a significant increase in the median urine albumin and urine osteoactivin in the AKI group, compared to the no AKI group (p = 0.020 and p = 0.018, respectively). When normalized to urine creatinine (UCr), an increased log osteoactivin/UCr was associated with higher odds of AKI development (OR: 2.05; 95% CI: 1.07, 4.44; p = 0.028), and higher log epidermal growth factor (EGF)/UCr (OR: 0.41; 95% CI: 0.15, 0.96) was associated with decreased odds of AKI. CONCLUSIONS: Early increase in urine osteoactivin is associated with AKI development within 7 days of MCS initiation in pediatric patients. Contrary, an increased urine EGF is associated with kidney protection. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Injúria Renal Aguda , Fator de Crescimento Epidérmico , Humanos , Criança , Estudos Retrospectivos , Biomarcadores/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Creatinina/urina , Fatores de Transcrição
5.
Mol Ther ; 31(7): 2240-2256, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37016577

RESUMO

Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol-requiring enzyme-1 (IRE1) operates as a central ER stress sensor, enabling the establishment of adaptive and repair programs through the control of the expression of the transcription factor X-box binding protein 1 (XBP1). To artificially enforce the adaptive capacity of the UPR in the AD brain, we developed strategies to express the active form of XBP1 in the brain. Overexpression of XBP1 in the nervous system using transgenic mice reduced the load of amyloid deposits and preserved synaptic and cognitive function. Moreover, local delivery of XBP1 into the hippocampus of an 5xFAD mice using adeno-associated vectors improved different AD features. XBP1 expression corrected a large proportion of the proteomic alterations observed in the AD model, restoring the levels of several synaptic proteins and factors involved in actin cytoskeleton regulation and axonal growth. Our results illustrate the therapeutic potential of targeting UPR-dependent gene expression programs as a strategy to ameliorate AD features and sustain synaptic function.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Estresse do Retículo Endoplasmático/genética , Camundongos Transgênicos , Proteômica , Proteostase/genética , Transdução de Sinais/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resposta a Proteínas não Dobradas/genética
6.
Z Gastroenterol ; 62(4): 500-507, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37729942

RESUMO

Cystic echinococcosis (CE) is a worldwide helminthic zoonosis causing serious disease in humans. The WHO Informal Working Group on Echinococcosis recommends a stage-specific treatment approach of hepatic CE that facilitates the decision on what therapy option is most appropriate. Percutaneous aspiration, instillation of a scolicide, e.g., ethanol or hypertonic saline, and subsequent re-aspiration (PAIR) have been advocated for treating medium-size unilocular WHO-stage CE1 cysts. PAIR can pose a risk of toxic cholangitis because of spillage of ethanol in the case of a cysto-biliary fistula or of life-threatening hypernatriaemia when hypertonic saline is used. The purpose of our study is to develop an alternative, safe, minimally invasive method to treat CE1 cysts, avoiding the use of toxic topic scolicides.We opt for percutaneous drainage (PD) in four patients: the intrahepatic drainage catheter is placed under CT-fluoroscopy, intracystic fluid is aspirated, and the viability of intracystic echinococcal protoscolices is assessed microscopically. Oral praziquantel (PZQ) is added to albendazole (ABZ) instead of using topical scolicidals.Protoscolices degenerate within 5 to 10 days after PZQ co-medication at a cumulative dosage of 250 to 335 mg/kg, and the cysts collapse. The cysts degenerate, and no sign of spillage nor relapse is observed in the follow-up time of up to 24 months post-intervention.In conclusion, PD combined with oral PZQ under ABZ coverage is preferable to PAIR in patients with unilocular echinococcal cysts.


Assuntos
Cistos , Equinococose Hepática , Equinococose , Humanos , Albendazol/uso terapêutico , Praziquantel/uso terapêutico , Recidiva Local de Neoplasia , Equinococose/tratamento farmacológico , Drenagem , Equinococose Hepática/diagnóstico , Equinococose Hepática/tratamento farmacológico , Cistos/tratamento farmacológico , Etanol , Fígado
7.
Kidney Int ; 103(6): 1093-1104, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36921719

RESUMO

Transcriptional profiling studies have identified several protective genes upregulated in tubular epithelial cells during acute kidney injury (AKI). Identifying upstream transcriptional regulators could lead to the development of therapeutic strategies augmenting the repair processes. SOX9 is a transcription factor controlling cell-fate during embryonic development and adult tissue homeostasis in multiple organs including the kidneys. SOX9 expression is low in adult kidneys; however, stress conditions can trigger its transcriptional upregulation in tubular epithelial cells. SOX9 plays a protective role during the early phase of AKI and facilitates repair during the recovery phase. To identify the upstream transcriptional regulators that drive SOX9 upregulation in tubular epithelial cells, we used an unbiased transcription factor screening approach. Preliminary screening and validation studies show that zinc finger protein 24 (ZFP24) governs SOX9 upregulation in tubular epithelial cells. ZFP24, a Cys2-His2 (C2H2) zinc finger protein, is essential for oligodendrocyte maturation and myelination; however, its role in the kidneys or in SOX9 regulation remains unknown. Here, we found that tubular epithelial ZFP24 gene ablation exacerbated ischemia, rhabdomyolysis, and cisplatin-associated AKI. Importantly, ZFP24 gene deletion resulted in suppression of SOX9 upregulation in injured tubular epithelial cells. Chromatin immunoprecipitation and promoter luciferase assays confirmed that ZFP24 bound to a specific site in both murine and human SOX9 promoters. Importantly, CRISPR/Cas9-mediated mutation in the ZFP24 binding site in the SOX9 promoter in vivo led to suppression of SOX9 upregulation during AKI. Thus, our findings identify ZFP24 as a critical stress-responsive transcription factor protecting tubular epithelial cells through SOX9 upregulation.


Assuntos
Injúria Renal Aguda , Fatores de Transcrição SOX9 , Animais , Humanos , Camundongos , Injúria Renal Aguda/prevenção & controle , Células Epiteliais/metabolismo , Rim/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Regulação para Cima , Dedos de Zinco
8.
Parasitol Res ; 122(8): 1811-1818, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37272973

RESUMO

Echinococcosis is a life-threatening neglected zoonotic disease. Cystic echinococcosis (CE) due to Echinococcus (E.) granulosus usually involves livestock and dogs; alveolar echinococcosis (AE) due to E. multilocularis involves rodents and canines such as foxes and dogs. Human hosts are infected accidentally via hand to mouth and/or foodborne/waterborne pathways. Albania is deemed to be endemic for cystic echinococcosis (CE), but there is a scarcity of data to confirm this. A systematic literature search was performed in PubMed, Google Scholar, and in other medical sources. Because of the scarcity of existing information, data confirming CE cases were reviewed from the medical hospital records of Albania's largest Hospital, the Mother Teresa University Hospital (UHCMT) Tirana, and from a large private laboratory in Tirana (Pegasus laboratory). A total of eight eligible publications on 540 CE patients were found. Three hundred forty seven additional cases hospitalized in UHCMT from 2011 to 2020 were confirmed, as well as 36 laboratory cases and 10 Albanian cases notified in Germany. Taking all cases into account and considering 162 overlapping cases, 771 cases were documented from 2011 to 2020. The only case reported as AE was most likely a multi-organic CE. Surgery was the most frequent therapy approach used (84.7%). Autochthonous human CE seems to be widespread, and transmission is ongoing in Albania. CE patients in Albania undergo surgery more frequently compared with CE cases in other European countries. In order to establish a realistic estimate of prevalence and incidence of CE in Albania, mandatory notification should be reinforced. Stage-specific therapy can be used in CE to reduce therapy cost and diminish mortality by avoiding surgical overtreatment.


Assuntos
Equinococose , Echinococcus granulosus , Echinococcus , Humanos , Animais , Cães , Albânia/epidemiologia , Equinococose/epidemiologia , Equinococose/veterinária , Zoonoses/epidemiologia
9.
Mol Hum Reprod ; 28(3)2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35201340

RESUMO

Mammalian sperm capacitation is a prerequisite for successful fertilization. Capacitation involves biochemical and physiological modifications of sperm as they travel through the female reproductive tract. These modifications prepare the sperm to undergo the acrosome reaction (AR), an acrosome vesicle exocytosis that is necessary for gamete fusion. Capacitation requires an increase in both intracellular calcium ([Ca2+]i) and pH (pHi). Mouse sperm capacitation is accompanied by acrosomal alkalinization and artificial elevation of the acrosome pH (pHa) is sufficient to trigger the AR in mouse and human sperm, but it is unknown if pHa increases naturally during human sperm capacitation. We used single-cell imaging and image-based flow cytometry to evaluate pHa during capacitation and its regulation. We found that pHa progressively increases during capacitation. The V-ATPase, which immunolocalized to the acrosome and equatorial segment, is mainly responsible for the acidity of the acrosome. It is likely that the regulation of V-ATPase is at least in part responsible for the progressive increase in pHa during capacitation. Acrosome alkalinization was dependent on extracellular HCO3- and Ca2+. Inhibition of the HCO3--dependent adenylyl cyclase and protein kinase A induced significant pHa changes. Overall, alkalinization of the acrosome may be a key step in the path toward the AR.


Assuntos
Reação Acrossômica , Cálcio , Capacitação Espermática , Acrossomo/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Cálcio/metabolismo , Humanos , Masculino , Mamíferos , Camundongos , Capacitação Espermática/fisiologia , Espermatozoides/metabolismo
10.
Sensors (Basel) ; 22(15)2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-35957448

RESUMO

Deep neural networks have demonstrated the capability of solving classification problems using hierarchical models, and fuzzy image preprocessing has proven to be efficient in handling uncertainty found in images. This paper presents the combination of fuzzy image edge-detection and the usage of a convolutional neural network for a computer vision system to classify guitar types according to their body model. The focus of this investigation is to compare the effects of performing image-preprocessing techniques on raw data (non-normalized images) with different fuzzy edge-detection methods, specifically fuzzy Sobel, fuzzy Prewitt, and fuzzy morphological gradient, before feeding the images into a convolutional neural network to perform a classification task. We propose and compare two convolutional neural network architectures to solve the task. Fuzzy edge-detection techniques are compared against their classical counterparts (Sobel, Prewitt, and morphological gradient edge-detection) and with grayscale and color images in the RGB color space. The fuzzy preprocessing methodologies highlight the most essential features of each image, achieving favorable results when compared to the classical preprocessing methodologies and against a pre-trained model with both proposed models, as well as achieving a reduction in training times of more than 20% compared to RGB images.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos
11.
Trop Anim Health Prod ; 54(2): 94, 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35137322

RESUMO

The aims were to study the epidemiology and the effect of gastrointestinal nematodes (GINs) on yearling cattle in a semiarid region in Argentina and to evaluate the mineral serum levels. Ten- to twelve-month-old calves were monitored between November and April 2019. Animals were divided into three groups: untreated control (CONG; n = 20); group treated with moxidectin (MXD, 200 µg/kg) every 30-40 days (MXDG; n = 20); group equally MXD treated and mineral supplementation administered in November and January (MMG; n = 20). Individual GIN egg counts (epg) and fecal cultures were made every 30-40 days. Animal live weight gain was determined. On 7-11-18, 25-1-19, and 3-4-19, serum levels of Se, Cu, Zn, Mg, and Ca were determined by atom absorption spectrophotometry. At the start of the trial, epg values were low (x̄ = 5.5), which increased only in CONG towards the end of the assay (x̄ = 229). In both GMXD and MMG, epg remained very low (x̄ = 4.1). Cooperia spp. (81%) prevailed over Haemonchus spp. (9%) and Oesophagostomum spp. (9%). Deficiency of Se ranged between marginal and important, except for MMG, although mean values were always below normal. Cu was marginally deficient in CONG and MXDG on the first two sampling dates, whereas MMG had normal values after treatment. Mg had low values in the three groups (x̄ = 1.5 mg/dl), whereas Ca and Zn exhibited normal values. Live weight gain (LWG) was higher in MMG than in MXDG, with significant differences (p < 0.05) by mid-January and then, when epg increased, dewormed groups showed higher LWG (p < 0.034) than CONG. A negative effect of GINs on LWG was observed, as well as low to marginal levels of Se, Cu, and Mg.


Assuntos
Doenças dos Bovinos , Nematoides , Infecções por Nematoides , Animais , Argentina/epidemiologia , Bovinos , Doenças dos Bovinos/epidemiologia , Fezes , Trato Gastrointestinal , Infecções por Nematoides/epidemiologia , Infecções por Nematoides/veterinária , Contagem de Ovos de Parasitas/veterinária
12.
J Med Virol ; 93(4): 2099-2114, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33049069

RESUMO

The genomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide are publicly available and are derived from studies due to the increase in the number of cases. The importance of study of mutations is related to the possible virulence and diagnosis of SARS-CoV-2. To identify circulating mutations present in SARS-CoV-2 genomic sequences in Mexico, Belize, and Guatemala to find out if the same strain spread to the south, and analyze the specificity of the primers used for diagnosis in these samples. Twenty three complete SARS-CoV-2 genomic sequences, available in the GISAID database from May 8 to September 11, 2020 were analyzed and aligned versus the genomic sequence reported in Wuhan, China (NC_045512.2), using Clustal Omega. Open reading frames were translated using the ExPASy Translate Tool and UCSF Chimera (v.1.12) for amino acid substitutions analysis. Finally, the sequences were aligned versus primers used in the diagnosis of COVID-19. One hundred and eighty seven distinct variants were identified, of which 102 are missense, 66 synonymous and 19 noncoding. P4715L and P5828L substitutions in replicase polyprotein were found, as well as D614G in spike protein and L84S in ORF8 in Mexico, Belize, and Guatemala. The primers design by CDC of United States showed a positive E value. The genomic sequences of SARS-CoV-2 in Mexico, Belize, and Guatemala present similar mutations related to a virulent strain of greater infectivity, which could mean a greater capacity for inclusion in the host genome and be related to an increased spread of the virus in these countries, furthermore, its diagnosis would be affected.


Assuntos
COVID-19/virologia , Genoma Viral , Mutação , SARS-CoV-2/genética , Belize , COVID-19/diagnóstico , Primers do DNA , Guatemala , Humanos , México , Fases de Leitura Aberta , Reação em Cadeia da Polimerase
13.
Mol Cell Biochem ; 476(10): 3815-3825, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34110554

RESUMO

Chagas and COVID-19 are diseases caused by Trypanosoma cruzi and SARS-CoV-2, respectively. These diseases present very different etiological agents despite showing similarities such as susceptibility/risk factors, pathogen-associated molecular patterns (PAMPs), recognition of glycosaminoglycans, inflammation, vascular leakage hypercoagulability, microthrombosis, and endotheliopathy; all of which suggest, in part, treatments with similar principles. Here, both diseases are compared, focusing mainly on the characteristics related to dysregulated immunothrombosis. Given the in-depth investigation of molecules and mechanisms related to microthrombosis in COVID-19, it is necessary to reconsider a prompt treatment of Chagas disease with oral anticoagulants.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/patologia , Doença de Chagas/patologia , Heparitina Sulfato/uso terapêutico , Trombose/tratamento farmacológico , Trombose/patologia , Plaquetas/imunologia , COVID-19/imunologia , Doença de Chagas/imunologia , Ativação do Complemento/imunologia , Endotélio/patologia , Humanos , Moléculas com Motivos Associados a Patógenos/imunologia , Ativação Plaquetária/imunologia , SARS-CoV-2/imunologia , Trypanosoma cruzi/imunologia
14.
BMC Infect Dis ; 21(1): 1241, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895157

RESUMO

BACKGROUND: Living conditions in homeless shelters facilitate the transmission of COVID-19. Social determinants and pre-existing health conditions place homeless people at increased risk of severe disease. Described outbreaks in homeless shelters resulted in high proportions of infected residents and staff members. In addition to other infection prevention strategies, regular shelter-wide (universal) testing for COVID-19 may be valuable, depending on the level of community transmission and when resources permit. METHODS: This was a prospective feasibility cohort study to evaluate universal testing for COVID-19 at a homeless shelter with 106 beds in Berlin, Germany. Co-researchers were recruited from the shelter staff. A PCR analysis of saliva or self-collected nasal/oral swab was performed weekly over a period of 3 weeks in July 2020. Acceptability and implementation barriers were analyzed by process evaluation using mixed methods including evaluation sheets, focus group discussion and a structured questionnaire. RESULTS: Ninety-three out of 124 (75%) residents were approached to participate in the study. Fifty-one out of the 93 residents (54.8%) gave written informed consent; thus 41.1% (51 out of 124) of all residents were included in the study. Among these, high retention rates (88.9-93.6%) of a weekly respiratory specimen were reached, but repeated collection attempts, as well as assistance were required. Around 48 person-hours were necessary for the sample collection including the preparation of materials. A self-collected nasal/oral swab was considered easier and more hygienic to collect than a saliva specimen. No resident was tested positive by RT-PCR. Language barriers were the main reason for non-participation. Flexibility of sample collection schedules, the use of video and audio materials, and concise written information were the main recommendations of the co-researchers for future implementation. CONCLUSIONS: Voluntary universal testing for COVID-19 is feasible in homeless shelters. Universal testing of high-risk facilities will require flexible approaches, considering the level of the community transmission, the available resources, and the local recommendations. Lack of human resources and laboratory capacity may be a major barrier for implementation of universal testing, requiring adapted approaches compared to standard individual testing. Assisted self-collection of specimens and barrier free communication may facilitate implementation in homeless shelters. Program planning must consider homeless people's needs and life situation, and guarantee confidentiality and autonomy.


Assuntos
COVID-19 , Pessoas Mal Alojadas , Teste para COVID-19 , Estudos de Coortes , Estudos de Viabilidade , Alemanha , Humanos , Estudos Prospectivos , SARS-CoV-2
15.
Prenat Diagn ; 41(8): 983-988, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33591585

RESUMO

OBJECTIVE: To evaluate if magnesium sulfate (MgSO4 ) titration following fetoscopic spina bifida closure is associated with fewer maternal complications than the Management of Myelomeningocele Study (MOMS) tocolytic regimen. METHODS: This prospective cohort study included 73 consecutive patients undergoing fetoscopic closure of spina bifida between 2015 and 2020. A policy of using the MgSO4 regimen per the MOMS trial was changed to a flexible one in which MgSO4 was titrated according to the frequency of the uterine contractions following surgery. The frequency of maternal pulmonary edema, low maternal oxygen saturation requiring oxygen supplementation, atelectasis, hypocalcemia, and preterm delivery was compared before and after the policy was changed. RESULTS: A higher proportion of women in the group that used the MOMS MgSO4 regimen had pulmonary edema compared to those in the flexible one (26.1% [6/23] vs. 6% [3/50]; p = 0.024). Multivariate analysis showed that the MOMS tocolytic regimen was independently associated with a higher risk of pulmonary edema (adjusted odds ratio: 8.57; 95% confidence interval: 1.54-47.7; p = 0.014) than a flexible one. There was no difference in the rate of preterm delivery. CONCLUSION: Following fetoscopic closure of spina bifida, the MOMS MgSO4 regimen is associated with an increased risk of pulmonary edema than a more flexible regimen.


Assuntos
Relação Dose-Resposta a Droga , Fetoscopia/efeitos adversos , Sulfato de Magnésio/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Disrafismo Espinal/cirurgia , Adulto , Estudos de Coortes , Feminino , Fetoscopia/métodos , Fetoscopia/estatística & dados numéricos , Idade Gestacional , Humanos , Complicações Pós-Operatórias/tratamento farmacológico , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Disrafismo Espinal/tratamento farmacológico
16.
Gynecol Endocrinol ; 37(10): 906-913, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34379025

RESUMO

OBJECTIVE: To evaluate the safety and tolerability of an oral herbal supplement containing glucosinolates, phytosterols, and citrus flavonoids (Warmi®, Lima Perú;) in otherwise healthy adult women. METHODS: This was a phase-I, randomized parallel three arms, double-blinded, and a placebo-controlled clinical trial. A total of 55 participants aged 18-40 were randomly assigned to one of three groups to receive for three months: (1) an oral herbal supplement of 1650 mg/day; (2) an oral herbal supplement of 3300 mg/day; or (3) an oral placebo 3300 mg/day. The primary endpoints were oral safety and tolerability of the supplement. The secondary endpoint was its effect on vital functions, anthropometrics, and laboratory tests. We used an exploratory approach by covariance analysis (ANCOVA) adjusted for the variables' baseline value for the secondary outcomes. RESULTS: All women completed three months of follow-up, reporting no side effects. Our exploratory analysis revealed that treatment with the herbal supplement of 1650 mg/day was associated with increased glucose and uric acid levels. In comparison, the herbal supplement 3300 mg/day was associated with reduced breathing rate, increased basal temperature, and systolic blood pressure, both compared to the placebo group. However, despite significant differences, none of these was clinically significant. CONCLUSION: The oral herbal supplement had a favorable safety and tolerability profile in studied women. There is a need to study its potential as an option to treat menopausal symptoms.


Assuntos
Citrus/química , Flavonoides/administração & dosagem , Glucosinolatos/administração & dosagem , Fitosteróis/administração & dosagem , Preparações de Plantas/efeitos adversos , Adulto , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Menopausa/efeitos dos fármacos , Placebos , Preparações de Plantas/administração & dosagem , Resultado do Tratamento
17.
Brain Inj ; 35(7): 842-849, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33678100

RESUMO

Background: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their condition.Objective: To identify protonation through in silico simulations of molecules involved in the process of coagulation in standard laboratory tests.Materials and methods: Ten patients with TBI were selected from the intensive care unit in addition to ten "healthy control subjects", and another nine patients as "disease control subjects"; the latter being a comparative group, corresponding to subjects with diabetes mellitus 2 (DM2). Fibrinogen, FVII, FVIII, FIX, FX, and D-dimer in the presence of acidification were evaluated in 20 healthy subjects in order to compare clinical results with molecular dynamics (MD), and to explain proton interactions and coagulation molecules.Results: The TBI group presented a slight, non-significant increase in D-dimer; but this was not present in "disease control subjects". Levels of fibrinogen, FVII, FIX, FX, and D-dimer were affected in the presence of acidification. We observed that various specific residues of coagulation factors "trap" ions.Conclusion: Protonation of tissue factor and factor VIIa may favor anticoagulant mechanisms, and protonation does not affect ligand binding sites of GPIIb/IIIa (PAC1) suggesting other causes for the low affinity to PAC1.


Assuntos
Lesões Encefálicas Traumáticas , Prótons , Coagulação Sanguínea , Lesões Encefálicas Traumáticas/complicações , Humanos , Simulação de Dinâmica Molecular
18.
Rev Argent Microbiol ; 53(2): 145-153, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-32928595

RESUMO

The objective of this work was to determine the seroprevalence of Neospora caninum in cattle in Valle de Lerma, province of Salta, Argentina, and the risk factors associated with the disease. Serum samples were taken from 40 cows in each dairy herd, which were analyzed by indirect ELISA to detect antibodies against N. caninum. Chronic and acute infections were discriminated by measuring the avidity of these antibodies. All the herds exhibited at least one seropositive animal, the mean being 35.3 ± 14.9% of positive animals. Specific antibodies were also detected in dogs present in 9of the herds, which showed a seropositivity value of 71.7% ± 19.9%. Among the seropositive animals, 56.3% showed acute infections. A negative association was found between seroprevalence and the avidity index of specific antibodies, indicating that the presence of animals with acute infections is associated with higher seroprevalence. Fields with grazing showed more recent infections. These results show for the first time the importance of this parasite in this particular region and the need to promote the development of control programs considering the different risk factors that affect the epidemiological situation of the disease.


Assuntos
Doenças dos Bovinos , Coccidiose , Neospora , Animais , Anticorpos Antiprotozoários , Argentina/epidemiologia , Bovinos , Doenças dos Bovinos/epidemiologia , Coccidiose/epidemiologia , Coccidiose/veterinária , Cães , Ensaio de Imunoadsorção Enzimática , Fazendas , Feminino , Fatores de Risco , Estudos Soroepidemiológicos
19.
Air Med J ; 40(2): 102-107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33637271

RESUMO

OBJECTIVE: The optimal patient transportation destination of acute ischemic stroke (AIS) patients remains uncertain. The purpose of this study was to evaluate the predictive variables that determine stroke outcomes depending on the patient transportation destination. METHODS: We performed a retrospective study using an AIS database consisting of patients who underwent thrombectomy admitted to our institution from November 1, 2011, through October 1, 2018. RESULTS: A total of 171 patients were included in the statistical analysis; 42.1% (72/171) of patients were in the mothership group (directly admitted) and 57.9% (99/171) in the drip-and-ship group (transferred). Multivariable logistic regression revealed the predictive factors for favorable outcomes were driving distance (expressed in miles) between the patient's home and a comprehensive stroke center (CSC) (odds ratio [OR] = 0.95; 95% confidence interval [CI], 0.90-0.99; P = .035), absence of diabetes mellitus (OR = 3.60; 95% CI, 1.20-10.82; P = .022), lower National Institutes of Health Stroke Scale score at admission (OR = 0.91; 95% CI, 0.85-0.97; P = .003), and shorter symptom onset to CSC arrival time (expressed in hours) (OR = 0.84; 95% CI, 0.72-0.99; P = .038). CONCLUSIONS: Our study revealed that a shorter driving distance between the patient's home and CSC, absence of diabetes, lower National Institutes of Health Stroke Scale score, and shorter onset to hospital arrival time positively impacted the outcomes of endovascularly treated AIS patients.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Isquemia Encefálica/cirurgia , Humanos , Transferência de Pacientes , Estudos Retrospectivos , Acidente Vascular Cerebral/terapia , Trombectomia , Resultado do Tratamento
20.
Gac Med Mex ; 157(3): 313-317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34667322

RESUMO

INTRODUCTION: During the COVID-19 pandemic, adherence to hygiene measures is an objective aimed at reducing morbidity and mortality. OBJECTIVE: To evaluate adherence to hand hygiene and protection measures during the COVID-19 pandemic in a tertiary care hospital. METHODS: Cross-sectional study on health personnel handwashing at the five moments recommended by the World Health Organization, as well as on the use of specific personal protective equipment. RESULTS: One hundred and seventeen hand hygiene opportunities were observed in health personnel. Hand washing was observed in 40 (34 %) and omission in 76 (65 %). Adherence to the use of face shield was observed in five (4 %), and lack of adherence in 112 (96%). Adherence to the use of face mask was observed in 65 nursing professionals (87 %), with appropriate use of the mask in 56 of them (60 %) and use of face shield in one (1 %). CONCLUSION: Health personnel showed low proportions of adherence to hand hygiene and use of equipment for specific protection during the COVID-19 pandemic.


INTRODUCCIÓN: Ante la pandemia de COVID-19, el apego a las medidas de higiene es un objetivo para disminuir la morbimortalidad. OBJETIVO: Evaluar el apego a la higiene de manos y medidas de protección durante la pandemia de COVID-19 en un hospital de tercer nivel. MÉTODOS: Estudio transversal acerca del lavado de manos del personal de salud en los cinco tiempos recomendados por la Organización Mundial de la Salud, así como sobre el uso del equipo de protección personal específico. RESULTADOS: Fueron observadas 117 oportunidades de higiene de manos en personal de salud: 40 (34 %) respecto al lavado de manos y 76 (65 %) respecto a su omisión; sobre el apego al uso de careta en cinco (4 %) y sobre la falta de apego en 112 (96 %). Se identificó apego al uso de mascarilla en 65 profesionales de enfermería (87 %), uso adecuado de mascarilla en 56 de ellos (60 %) y uso de careta en uno (1 %). CONCLUSIÓN: El personal mostró baja proporción de apego a la higiene de manos y al uso de equipo para la protección específica durante la pandemia de COVID-19.


Assuntos
COVID-19/prevenção & controle , Fidelidade a Diretrizes/estatística & dados numéricos , Higiene das Mãos/estatística & dados numéricos , Equipamento de Proteção Individual/estatística & dados numéricos , Recursos Humanos em Hospital/estatística & dados numéricos , Estudos Transversais , Feminino , Higiene das Mãos/normas , Humanos , Masculino , Recursos Humanos em Hospital/normas , Estudos Prospectivos , Centros de Atenção Terciária , Fatores de Tempo
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