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1.
Arch Virol ; 168(5): 133, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37029230

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) causes porcine reproductive and respiratory syndrome (PRRS) worldwide, especially in domestic pigs, with an enormous economic impact, estimated at $664 million in losses every year to the pig industry. Current vaccines confer limited protection, and no direct-acting anti-PRRS treatment is available. Non-structural protein (NSP) 1ß, a cysteine-like protease (CLPro) of PRRSV plays an essential role in viral polyprotein processing, subgenomic RNA synthesis, and evasion of host innate immunity. Therefore, agents that interfere with the bioactivity of NSP1ß would be expected to inhibit virus replication. In this study, a porcine single-chain antibody (scFv)-phage display library was constructed and used as a tool for production of NSP1ß-specific porcine scFvs (pscFvs). The pscFvs to NSP1ß were linked to a cell-penetrating peptide to form cell-penetrating pscFvs (transbodies), which could be internalized and inhibit PRRSV replication in infected cells. A computer simulation indicated that the effective pscFvs used several residues in multiple complementarity determining regions (CDRs) to interact with multiple residues in the CLPro and C-terminal motifs, which might explain the mechanism of pscFv-mediated inhibition of virus replication. Although experiments are needed to determine the antiviral mechanism of the transbodies, the current data indicate that transbodies can potentially be applied for treatment and prevention of PRRSV infection.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Anticorpos de Cadeia Única , Animais , Simulação por Computador , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/farmacologia , Suínos , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , RNA Subgenômico
2.
J Assist Reprod Genet ; 39(10): 2413-2430, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36066723

RESUMO

Trinucleotide repeats (TNRs) are dispersed throughout the human genome. About 20 loci are related to human diseases, such as Huntington's disease (HD). A larger TNR instability is predominantly observed in the paternal germ cells in some TNR disorders. Suppressing the expansion during spermatogenesis can provide a unique opportunity to end the vicious cycle of genetic anticipation. Here, using an in vitro differentiation method to derive advanced spermatogenic cells, we investigated the efficacy of two therapeutic agents, araC (cytarabine) and aspirin, on stabilizing TNRs in spermatogenic cells. Two WT patient-derived induced pluripotent stem cell (iPSC) lines and two HD hiPSC lines, with 44 Q and 180 Q, were differentiated into spermatogonial stem cell-like cells (SSCLCs). Both HD cell lines showed CAG tract expansion in SSCLC. When treated with araC and aspirin, HD1 showed moderate but not statistically significant stabilization of TNR. In HD2, 10 nM of aspirin and araC showed significant stabilization of TNR. All cell lines showed increased DNA damage response (DDR) gene expression in SSCLCs while more genes were significantly induced in HD SSCLC. In HD1, araC and aspirin treatment showed general suppression of DNA damage response genes. In HD2, only FAN1, OGG1, and PCNA showed significant suppression. When the methylation profile of HD cells was analyzed, FAN1 and OGG1 showed significant hypermethylation after the aspirin and araC treatment in SSCLC compared to the control. This study underscores the utility of our in vitro spermatogenesis model to study and develop therapies for TNR disorders such as HD.


Assuntos
Doença de Huntington , Expansão das Repetições de Trinucleotídeos , Masculino , Humanos , Expansão das Repetições de Trinucleotídeos/genética , Doença de Huntington/tratamento farmacológico , Doença de Huntington/genética , Antígeno Nuclear de Célula em Proliferação/genética , Repetições de Trinucleotídeos/genética , Células Germinativas , Citarabina , Aspirina
3.
Ann Surg ; 269(1): 108-113, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-28742692

RESUMO

OBJECTIVE: To determine the toxicity and oncologic outcome of neoadjuvant chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME) in the elderly (≥70 yrs) and younger (<70 yrs) rectal cancer patients. BACKGROUND: Sufficient data for elderly rectal cancer patients who received definitive trimodality have not been accumulated yet. PATIENTS AND METHODS: A total of 1232 rectal cancer patients who received neoadjuvant CRT and TME were enrolled in this study. After propensity-score matching, 310 younger patients and 310 elderly patients were matched with 1:1 manner. Treatment response, toxicity, surgical outcome, recurrence, and survival were assessed and compared between the 2 groups of patients. RESULTS: The median age was 58 years for the younger patient group and 74 years for the elderly group. Pathologic complete response rates were not significantly different between the 2 groups (younger and elderly: 17.1% vs 14.8%, P = 0.443). The 5-year recurrence-free survival (younger and elderly: 67.7% vs 65.5%, P = 0.483) and overall survival (younger and elderly: 82.9% vs. 79.5%, P = 0.271) rates were not significantly different between the 2 groups either. Adjuvant chemotherapy after surgery was less frequently delivered to the elderly than that to younger patients (83.9% vs 69.0%). Grade 3 or higher acute hematologic toxicity was observed more frequently in the elderly than that in the younger group (9.0% vs 16.1%, P = 0.008). Late complication rate was higher in the elderly group compared with that in the younger group without statistical significance (2.6% vs 4.5%, P = 0.193). CONCLUSIONS: Although acute hematologic toxicity was observed more frequently in the elderly patients than that in the younger patients, elderly rectal cancer patients with good performance status who received preoperative CRT and TME showed favorable tumor response and recurrence-free survival similar to younger patients.


Assuntos
Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Colectomia/métodos , Recidiva Local de Neoplasia/epidemiologia , Cuidados Pré-Operatórios/métodos , Pontuação de Propensão , Neoplasias Retais/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimiorradioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/diagnóstico , Neoplasias Retais/mortalidade , Reto/cirurgia , República da Coreia/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências
4.
Cardiol Young ; 28(8): 1037-1041, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29962357

RESUMO

We examined whether hypotension in very low birth weight infants aged⩽1 week was associated with hospital morbidities and overall mortality. Further, we studied whether hypotension was associated with poor neurodevelopmental outcomes in these patients at the corrected age of 18 months. A total of 166 very low birth weight infants were studied during this period. Hospital outcomes and neurodevelopmental outcomes at the corrected age of 18 months were evaluated. Among the 166 very low birth weight infants, 95 patients (57.2%) experienced hypotension at⩽1 week and were associated with an increased incidence of morbidities and mortality. At the corrected age of 18 months, hypotension of the⩽1 week group had significantly lower scores in all three - cognitive, language, and motor - composites of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) screening tests. In addition, a multivariable logistic regression analysis showed that longer mechanical ventilation and periventricular leukomalacia were additionally associated with worse cognitive and language neurodevelopmental outcomes. Hypotension in very low birth weight infants within 1 week of life was associated with increased morbidities and overall mortality. It was also associated with an increased risk of cognitive and language outcomes.


Assuntos
Transtornos Cognitivos/epidemiologia , Deficiências do Desenvolvimento/epidemiologia , Hipotensão/epidemiologia , Mortalidade Infantil , Recém-Nascido de muito Baixo Peso , Transtornos do Desenvolvimento da Linguagem/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Escalas de Graduação Psiquiátrica , República da Coreia , Estudos Retrospectivos
5.
Pediatr Emerg Care ; 34(4): 243-249, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28169978

RESUMO

OBJECTIVE: Satellite pediatric emergency departments (PEDs) have emerged as a strategy to increase patient capacity. We sought to determine the impact on patient visits, physician fee collections, and value of emergency department (ED) time at the primary PED after opening a nearby satellite PED. We also illustrate the spatial distribution of patient demographics and overlapping catchment areas for the primary and satellite PEDs using geographical information system. METHODS: A structured, financial retrospective review was conducted. Aggregate patient demographic data and billing data were collected regarding physician fee charges, collections, and patient visits for both PEDs. All ED visits from January 2009 to December 2013 were analyzed. Geographical information system mapping using ArcGIS mapped ED patient visits. RESULTS: Patient visits at the primary PED were 53,050 in 2009 before the satellite PED opened. The primary PED visits increased after opening the satellite PED to 55,932 in 2013. The satellite PED visits increased to 21,590 in 2013. Collections per visit at the primary PED decreased from $105.13 per visit in 2011 to $86.91 per visit in 2013. Total collections at the satellite PED decreased per visit from $155.41 per visit in 2011 to $128.53 per visit in 2013. CONCLUSIONS: After opening a nearby satellite PED, patient visits at the primary PED did not substantially decrease, suggesting that there was a previously unrecognized demand for PED services. The collections per ED visit were greater at the satellite ED, likely due to a higher collection rate.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Hospitais Satélites/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Criança , Demografia , Serviço Hospitalar de Emergência/economia , Feminino , Hospitais Pediátricos/economia , Hospitais Satélites/economia , Humanos , Masculino , Estudos Retrospectivos
6.
Ann Surg Oncol ; 24(13): 3903-3910, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29039025

RESUMO

BACKGROUND: Contralateral prophylactic mastectomy (CPM) rates in younger women with unilateral breast cancer have more than doubled. Studies of cost and quality of life of the procedure remain inconclusive. METHODS: A cost-effectiveness analysis using a decision-tree model in TreeAge Pro 2015 was used to compare long-term costs and quality of life following unilateral mastectomy (UM) with routine surveillance versus CPM for sporadic breast cancer in women aged 45 years. A 10-year risk period for contralateral breast cancer (CBC), reconstruction, wound complications, cost of routine surveillance, and treatment for CBC were used to estimate accrued costs. In addition, a societal perspective was used to estimate quality-adjusted life years (QALYs) following either treatment for a period of 30 years. Medical costs were obtained from the 2014 Medicare physician fee schedule and event probabilities were taken from recent literature. RESULTS: The mean cost of UM with surveillance was $14,141 and CPM was $20,319. Treatment with CPM resulted in $6178 more in costs but equivalent QALYs (17.93) compared with UM over 30 years of follow-up. Even with worst-case scenario and varying assumptions, CPM is dominated by UM in terms of cost and quality. CONCLUSIONS: From this refined model, UM with routine surveillance costs less and provides an equivalent quality of life. Patients undergoing CPM may eliminate the anxiety of routine surveillance, but they face the burden of higher lifetime medical costs.


Assuntos
Neoplasias da Mama/economia , Análise Custo-Benefício , Mastectomia/economia , Mastectomia Profilática/economia , Qualidade de Vida , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/cirurgia , Árvores de Decisões , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco
7.
Pediatr Emerg Care ; 32(10): 726-730, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27749673

RESUMO

This article is the sixth in a 7-part series that aims to comprehensively describe the current state and future directions of pediatric emergency medicine (PEM) fellowship training from the essential requirements to considerations for successfully administering and managing a program to the careers that may be anticipated upon program completion. This article provides a broad overview of administering and supervising a PEM fellowship program. It explores 3 topics: the principles of program administration, committee management, and recommendations for minimum time allocated for PEM fellowship program directors to administer their programs.


Assuntos
Medicina de Emergência/educação , Medicina de Emergência Pediátrica/organização & administração , Pediatria/educação , Currículo , Avaliação Educacional , Bolsas de Estudo , Humanos , Internato e Residência , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários , Estados Unidos
8.
Pediatr Emerg Care ; 34(4): 291-297, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29601465
9.
Asian-Australas J Anim Sci ; 25(11): 1582-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25049520

RESUMO

This experiment was performed to investigate the effects of lysine (Lys) to DE ratio on growth performance, and carcass characterics in finishing barrows. Ninety six cross-bred finishing barrows ((Landrace×Yorkshire) ×Duroc, average BW 58.25±0.48 kg) were assigned as a randomized complete block design by 2 energy levels and 4 Lys:DE ratios on the basis of BW to one of 8 treatments with 3 replications with 4 animals per pen. The levels of DE and Lys:DE ratio for each treatment were i) DE 3.35 Mcal/kg, 1.5 g Lys/Mcal DE, ii) DE 3.35 Mcal/kg, 1.8 g Lys/Mcal DE, iii) DE 3.35 Mcal/kg, 2.1 g Lys/Mcal DE, iv) DE 3.35 Mcal/kg, 2.4 g Lys/Mcal DE, v) DE 3.60 Mcal/kg, 1.5 g Lys/Mcal DE, vi) DE 3.60 Mcal/kg, 1.8 g Lys/Mcal DE, vii) DE 3.60 Mcal/kg, 2.1 g Lys/Mcal DE, viii) DE 3.60 Mcal/kg, 2.4 g Lys/Mcal DE. During finishing period from 58 kg to 103 kg of BW, increased energy density in the diet increased (p<0.05) ADG and gain:feed ratio, but did not influence ADFI. As Lys:DE ratio was increased, ADG, ADFI and gain:feed ratio were improved in finishing barrows (p<0.05). There were positive interactions (p<0.05) between carcass weight, grade, and backfat thickness and energy density and Lys level (p<0.05). In conclusion, data from our current study suggest that maximum yields including ADG, gain:feed ratio, carcass weight and grade can be achieved by administrating finishing pigs with an ideal Lys:DE ratio, Lys 2.1 g/DE Mcal.

10.
Int J Tuberc Lung Dis ; 26(1): 50-56, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969429

RESUMO

BACKGROUND: The surgical treatment for non-tuberculous mycobacterial pulmonary disease (NTM-PD) has an important adjunctive role and reported outcomes have been generally good; however, the prognostic factors remain unclear.METHODS: Sixty-one patients with NTM-PD who underwent surgical resection for a therapeutic purpose from January 2000 to March 2017 at five affiliated institutions were enrolled. We explored the factors that influence complications and prognosis by retrospectively referring to the medical records.RESULTS: The mean age of the present cohort was 61.8 ± 11.4 years. The pathogen was Mycobacterium avium complex in 49 patients, M. abscessus in 5. The most common indications were refractory to medication in 39. The surgical techniques employed were lobectomy or further resection in 49, sublobar resection in 8, with video-assisted thoracoscopic surgery in 21. Sputum culture conversion rate was 95.1%. Univariate analysis of factors associated with deterioration revealed significant differences related to age (P = 0.025), pre-operative albumin level (P = 0.001) and development of postoperative complications (P = 0.037), while pre-operative albumin level alone was a significant factor in multivariate analysis (P = 0.009).CONCLUSION: Outcomes after resection were generally good in the present cases. Nutritional status, as indicated by albumin level, may affect prognosis after surgical treatment.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Idoso , Humanos , Pneumopatias/microbiologia , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas , Prognóstico , Estudos Retrospectivos
11.
Biomedicines ; 10(8)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-36009409

RESUMO

Huntington's Disease (HD) is an autosomal dominant disease that results in severe neurodegeneration with no cure. HD is caused by the expanded CAG trinucleotide repeat (TNR) on the Huntingtin gene (HTT). Although the somatic and germline expansion of the CAG repeats has been well-documented, the underlying mechanisms had not been fully delineated. Increased CAG repeat length is associated with a more severe phenotype, greater TNR instability, and earlier age of onset. The direct relationship between CAG repeat length and molecular pathogenesis makes TNR instability a useful measure of symptom severity and tissue susceptibility. Thus, we examined the tissue-specific TNR instability of transgenic nonhuman primate models of Huntington's disease. Our data show a similar profile of CAG repeat expansion in both rHD1 and rHD7, where high instability was observed in testis, liver, caudate, and putamen. CAG repeat expansion was observed in all tissue samples, and tissue- and CAG repeat size-dependent expansion was observed. Correlation analysis of CAG repeat expansion and the gene expression profile of four genes in different tissues, clusterin (CLU), transferrin (TF), ribosomal protein lateral stalk subunit P1 (RPLP1), and ribosomal protein L13a (RPL13A), showed a strong correlation with CAG repeat instability. Overall, our data, along with previously published studies, can be used for studying the biology of CAG repeat instability and identifying new therapeutic targets.

12.
ACS Omega ; 6(7): 4907-4920, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33644598

RESUMO

Two series of novel 4-oxoquinazoline-based N-hydroxypropenamides (9a-m and 10a-m) were designed, synthesized, and evaluated for their inhibitory and cytotoxicity activities against histone deacetylase (HDAC). The compounds showed good to potent HDAC inhibitory activity and cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer). In this series, compounds with the N-hydroxypropenamide functionality impeded at position 7 on the 4-oxoquinazoline skeleton (10a-m) were generally more potent than compounds with the N-hydroxypropenamide moiety at position 6 (9a-m). Also, the N 3-benzyl-substituted derivatives (9h-m, 10h-m) exhibited stronger bioactivity than the N 3-alkyl-substituted ones (9a-e, 10a-e). Two compounds 10l and 10m were the most potent ones. Their HDAC inhibitory activity (IC50 values, 0.041-0.044 µM) and cytotoxicity (IC50 values, 0.671-1.211 µM) were approximately 2- to 3-fold more potent than suberoylanilide hydroxamic acid (SAHA). Some compounds showed up to 10-fold more potent HDAC6 inhibition compared to their inhibitory activity in total HDAC extract assay. Analysis of selected compounds 10l and 10m revealed that these compounds strongly induced both early and late apoptosis and arrested SW620 cells at the G2/M phase. Docking studies were carried out on the HDAC6 isoform for series 10a-m and revealed some important features contributing to the inhibitory activity of synthesized compounds.

13.
Clin Exp Immunol ; 161(2): 298-305, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20491794

RESUMO

Statins are potent inhibitors of hydroxyl-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, and have emerged as potential anti-cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)-10, transforming growth factor (TGF)-beta and indoleamine-2,3-dioxygenase (IDO) by tumours, which induce a regulatory T cell (T(reg)) response. In this study, we investigated the effect of simvastatin on the production of IL-10, TGF-beta and IDO production and the proliferation of T(regs) using several cancer cell lines, and Lewis lung cancer (3LL) cells-inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292). The production of the immune regulatory markers IL-10, TGF-beta in 3LL and NCI-H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin-treated mice groups. Therefore, while simvastatin had an anti-proliferative effect, it also exhibited immune tolerance-promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth.


Assuntos
Tolerância Imunológica/efeitos dos fármacos , Neoplasias/imunologia , Sinvastatina/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Contagem de Células , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Citostáticos/farmacologia , Citostáticos/uso terapêutico , Fatores de Transcrição Forkhead/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Tolerância Imunológica/imunologia , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Interleucina-10/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Sinvastatina/uso terapêutico , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/metabolismo
14.
Public Health Nutr ; 13(3): 384-92, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19943998

RESUMO

OBJECTIVE: To explore the relationship between children and their parents in terms of various anthropometric parameters and obesity-related hormone levels and to identify early indicators for child obesity. DESIGN: Cross-sectional observational study. SETTING: Urban areas of Korea in 2005. SUBJECTS: A total 124 families with 7-year-old children participated. Anthropometric and blood biochemistry data and information concerning the children's lifestyles, dietary habits and parental and grandparental weight status were obtained. RESULTS: The mean values for all anthropometric parameters were greater in overweight children than in children of normal weight. Very close relationships existed between the anthropometric parameters of children and their parents. Children with two overweight parents showed the highest odds for being overweight (OR 7.62). The strong relationship between overweight children and grandparental and parental overweight, especially on the maternal side, suggests gender differences in the intergenerational transmission of body weight. We also noted a greater risk of being overweight in children with a parent with high serum leptin level. CONCLUSIONS: Grandparental and parental weight status and parental serum leptin levels enable us to identify childhood obesity at an early age and may help to counter the current epidemic of adult obesity.


Assuntos
Leptina/sangue , Sobrepeso/sangue , Sobrepeso/epidemiologia , Relações Pais-Filho , Adulto , Área Sob a Curva , Índice de Massa Corporal , Criança , Estudos Transversais , Características da Família , Comportamento Alimentar , Feminino , Humanos , Relação entre Gerações , Coreia (Geográfico) , Estilo de Vida , Masculino , Sobrepeso/etiologia , Sobrepeso/genética , Prevalência , Curva ROC , Fatores de Risco , Fatores Sexuais
15.
Clin Exp Ophthalmol ; 38(6): 620-8, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20584023

RESUMO

BACKGROUND: Transforming growth factor beta (TGF-beta) plays an important role in diabetic retinopathy. betaIG-H3 is a downstream target molecule of TGF-beta that may participate in the pathogenesis of diabetic retinopathy and in particular in the loss of pericytes during early pathological changes. METHODS: We observed bovine retinal pericytes apoptosis and the increased expression of TGF-beta and betaIG-H3 induced by high concentrations of glucose in the cell culture media. An anti-TGF-beta antibody was used to block glucose-induced retinal pericytes apoptosis. Retinal pericytes were also transfected with cDNA encodings either wild-type or mutant betaIG-H3 lacking Arg-Gly-Asp (RGD) sequences in order to validate the effects of betaIG-H3 and RGD signalling on retinal pericytes apoptosis. RESULTS: A cell death-detecting enzyme-linked immunosorbent assay revealed that 25 mM glucose significantly increased cell death compared with 5.5 mM glucose after 5 or 7 days of exposure (P < 0.01). High glucose significantly increased the TGF-beta levels as compared with 5.5 mM glucose after 5 days, and betaIG-H3 levels after 3, 5 and 7 days of exposure (P < 0.01). TGF-beta increased cell death and betaIG-H3 levels in a dose-dependent manner, with a maximal effect observed at 1 ng/mL. An anti-TGF-beta antibody nearly completely blocked high glucose-induced cell death. Wild-type betaIG-H3-transfected cells showed a significant increase in cell death as compared with mutant betaIG-H3-transfected (Mycb-c) cells, untransfected or mock-transfected cells. CONCLUSION: These results suggest that hyperglycaemia-induced expression of TGF-beta and betaIG-H3 contributes to accelerated retinal pericytes apoptosis. betaIG-H3 induces pericytes apoptosis through its RGD motif, which may constitute an important pathogenic mechanism leading to pericytes loss in diabetic retinopathy.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Glucose/farmacologia , Oligopeptídeos/metabolismo , Pericitos/patologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Bovinos , Sobrevivência Celular , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Proteínas da Matriz Extracelular/genética , Glucose/antagonistas & inibidores , Imunoglobulina G/farmacologia , Marcação In Situ das Extremidades Cortadas , Pericitos/metabolismo , Vasos Retinianos/patologia , Transfecção , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologia
16.
Pediatr Emerg Care ; 26(5): 349-56, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20404781

RESUMO

OBJECTIVE: Previous literature suggests that process-related factors (eg, time of day, patient volume) and patient-related factors (eg, acuity, socioeconomic status) are associated with premature departure from emergency departments. We sought to evaluate the relationship of these and other factors with premature departure in a large, unselected cohort of pediatric emergency department patients. METHODS: This study was a retrospective cohort analysis of visits to a single tertiary site during a 1-year period. Patients' zip codes determined assignment of census-based socioeconomic metrics. Multivariate regression identified factors associated with premature departure. Sensitivity and subset analyses were performed. Return visits within 48 hours after premature departure were also reviewed. RESULTS: There were 46,417 visits, of which 2164 were premature departures. In multivariate analysis, independent predictors of premature departures were arrival time, arrival month, arrival day of week, patient acuity, concurrent premature departures, arrival rate, arrival period average length of stay, and poverty rate. Aside from patient acuity and poverty rate, no patient-related factors were significant in multivariate analysis. These results were robust in sensitivity analysis across different multivariate models. Among premature departures, there were 120 return visits (5.5%), of which 15 were admitted (0.7%). There were no deaths. Acuity was similar between initial and subsequent visits. CONCLUSIONS: Process-related factors and individual patient acuity have the strongest influence on premature departure from the pediatric emergency department. Health care organizations concerned with premature departure should focus efforts on improving pediatric emergency process flow.


Assuntos
Acessibilidade aos Serviços de Saúde/organização & administração , Hospitais Pediátricos/estatística & dados numéricos , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Pacientes Desistentes do Tratamento , Transferência de Pacientes/organização & administração , Triagem/organização & administração , Criança , Serviço Hospitalar de Emergência , Seguimentos , Humanos , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo
17.
Water Sci Technol ; 61(8): 1975-86, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20388994

RESUMO

This study is to assess the future impact of climate change on hydrological behavior considering future vegetation canopy prediction and its propagation to nonpoint source pollution (NPS) loads. The SWAT (Soil and Water Assessment Tool) model was used for the assessment. For a forest dominant ChungjuDam watershed of South Korea, the MIROC3.2hires climate data of SRES A1B and B1 scenarios were adopted and downscaled for the watershed. The future vegetation canopy information was projected by the monthly relationship between Terra MODIS (MODerate resolution Imaging Spectroradiometer) LAI (Leaf Area Index) and temperature. The future predicted LAI increased up to 1.9 in 2080s April and October because of the temperature increase 3.6 degrees C and 5.3 degrees C respectively. By reflecting the future LAI changes, the future estimated percent changes of maximum annual dam inflow, SS, T-N, and T-P were + 42.5% in 2080s A1B,-35.6% in 2020s A1B,+73.7% in 2080s A1B and-21.0% in 2080s B1 scenario respectively. The increase of T-N load was from the increase of subsurface lateral flows and the groundwater recharges by the future rainfall increase. The decrease of T-P load was by decrease of sediment load during wet days because the effect of LAI increase is greater than the increase of rainfall.


Assuntos
Mudança Climática , Ecossistema , Plantas , Poluição da Água , Previsões , Modelos Biológicos , República da Coreia
18.
Exp Biol Med (Maywood) ; 245(10): 851-860, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32326758

RESUMO

IMPACT STATEMENT: Tumor hypoxia promotes cancer cell aggressiveness, and is strongly associated with poor prognosis across multiple tumor types. The hypoxic microenvironments inside tumors also limit the effectiveness of radiotherapy, chemotherapy, and immunotherapy. Several approaches to eliminate hypoxic state in tumors have been proposed to delay cancer progression and improve therapeutic efficacies. This review will summarize current knowledge on hyperoxia, used alone or in combination with other therapeutic modalities, in cancer treatment. Molecular mechanisms and undesired side effects of hyperoxia will also be discussed.


Assuntos
Hipóxia Celular/fisiologia , Neoplasias/terapia , Oxigenoterapia/métodos , Humanos , Neoplasias/fisiopatologia
19.
Pediatr Emerg Care ; 25(6): 387-92, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19458561

RESUMO

OBJECTIVE: We sought to determine the use and results of urine toxicology screens (UTS) in psychiatric patients undergoing a UTS test for medical clearance in a pediatric emergency department. METHODS: A structured retrospective study was conducted over a 6-month period. All emergency department (ED) charts were reviewed of patients 8 to 17 years who had a UTS. Urine toxicology screens were identified as medically indicated or routine-driven. Medically indicated UTS were patients who presented with seizures, syncope, headache, altered mental status, ingestion, chest pain/palpitation, shortness of breath, sexual assault, or those who were brought in for motor vehicle accident (MVA). Routine-driven UTS were uncomplicated psychiatric patients who presented with aggressive or out of control behavior, intentional self-inflicted wounds, or symptoms of depression, all of whom presented without any evidence of drug or alcohol ingestion or altered mental status. Routine-driven UTS were quantified for positive tests. In addition, we determined the change in management and disposition of those patients. We also determined the concordance of provided drug use history with UTS result. RESULTS: Of the 652 charts reviewed, 267 UTS were medically indicated; 385 were routine-driven. Of the routine-driven UTS group, 254/267 (95%) patients with negative screens and 115/118 (97%) with positive screens were referred for psychiatric treatment after psychiatric evaluation. Fisher exact test of the comparison of the disposition after psychiatric assessment with the UTS result was nonsignificant. The UTS result also had no effect on the type of psychiatric disposition (ie, outpatient therapy, partial hospitalization, inpatient hospitalization). Concordance with provided history of illicit drug use was significant. CONCLUSIONS: Routine-driven UTS in uncomplicated pediatric psychiatric patients being evaluated in the ED offered little additional information, did not influence management, and potentially increased both ED cost and time. Patients with straightforward psychiatric complaints may be medically cleared without a UTS.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Drogas Ilícitas/urina , Pessoas Mentalmente Doentes/estatística & dados numéricos , Detecção do Abuso de Substâncias/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/urina , Urinálise/estatística & dados numéricos , Acidentes de Trânsito , Adolescente , Criança , Comorbidade , Enganação , Grupos Diagnósticos Relacionados , Testes Diagnósticos de Rotina/estatística & dados numéricos , Feminino , Humanos , Masculino , Transtornos Mentais/urina , Doenças do Sistema Nervoso/urina , Variações Dependentes do Observador , Recidiva , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Comportamento Autodestrutivo/urina , Delitos Sexuais , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia
20.
Trop Biomed ; 36(1): 152-164, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33597435

RESUMO

This study aimed to determine the prevalence and intensity of intestinal helminth infections (IHIs) among rural villagers in Waeng Noi district, Khon Kaen Province, northeastern Thailand. A cross-sectional study was conducted between March 1 and July 30, 2018, among rural villagers from 30 rural villages in 2 subdistricts. The participants were selected from the village enrollment list after proportional allocation of the total sample size. The background characteristic data were collected using a structured questionnaire. Specimens from patients with IHIs were prepared by concentration with a Faecal Parasite Concentrator-Solvent-Free (Mini Parasep® SF), and helminths were then detected using a light microscope. Of the 400 faecal specimens examined, 23 were positive for at least one intestinal helminth, resulting in a prevalence of 5.75%. The most prevalent helminths were Taenia spp., 10 (2.50%); followed by hookworm, 5 (1.25%); Trichuris trichiura, 4 (1.0%); Ascaris lumbricoides, 3(0.50%); and Opisthorchis viverrini, 1 (0.25%). All infected participants had a light intensity of IHI. Location (adjusted OR=2.52; 95% CI=1.30-3.52; P =0.042) showed a significant association with the prevalence of intestinal helminths. This study reveals that IHIs, particularly those with foodborne and soil-transmitted species of helminths, are prevalent in adults in rural subdistricts. A greater focus on interventions to improve personal hygiene and sanitation to prevent the spread of IHIs is required. Further studies should be performed to implement interdisciplinary research approaches in the study area.

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