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1.
Med Mycol ; 62(10)2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39327022

RESUMO

Azole resistance has emerged as a new therapeutic challenge in patients with aspergillosis. Various resistance mutations are attributed to the widespread use of triazole-based fungicides in agriculture. This study explored the prevalence of azole-resistant Aspergillus fumigatus (ARAF) and other aspergilli in the Argentine environment. A collection of A. fumigatus and other aspergilli strains isolated from soil of growing crops, compost, corn, different animal feedstuffs, and soybean and chickpea seeds were screened for azole resistance. No ARAF was detected in any of the environmental samples studied. However, five A. flavus, one A. ostianus, one A. niger and one A. tamarii recovered from soybean and chickpea seeds showed reduced susceptibility to medical azole antifungals (MAA). The susceptibility profiles of five A. flavus isolates, showing reduced susceptibility to demethylase inhibitors (DMIs), were compared with those of 10 isolates that exhibited susceptibility to MAA. Aspergillus flavus isolates that showed reduced MAA susceptibility exhibited different susceptibility profiles to DMIs. Prothioconazole and tebuconazole were the only DMIs significantly less active against isolates with reduced susceptibility to MAA. Although no ARAF isolates were found in the samples analysed, other aspergilli with reduced susceptibility profile to MAA being also important human pathogens causing allergic, chronic and invasive aspergillosis, are present in the environment in Argentina. Although a definitive link between triazole-based fungicide use and isolation of azole-resistant human pathogenic aspergilli from agricultural fields in Argentina remains elusive, this study unequivocally highlights the magnitude of the environmental spread of azole resistance among other Aspergillus species.


This study intended to inform about the prevalence of Aspergillus species showing triazole resistance in the Argentinian environment. Since azole fungicides are used for crop protection, it was expected that azole resistance in this species with cross-resistance to medical azoles could occur.


Assuntos
Antifúngicos , Azóis , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Argentina/epidemiologia , Azóis/farmacologia , Antifúngicos/farmacologia , Prevalência , Microbiologia Ambiental , Microbiologia do Solo , Aspergillus/efeitos dos fármacos , Aspergillus/isolamento & purificação , Aspergillus/genética , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Humanos , Aspergilose/microbiologia , Aspergilose/epidemiologia
2.
Rev Argent Microbiol ; 54(3): 243-246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35654655

RESUMO

In Argentina there are no reports on Aspergillus fumigatus fumagillin-producing strains. In this study we describe the isolation and mycotoxin production capacity of ten A. fumigatus strains isolated from farm and clinical samples. Farm strains were isolated from milk samples taken from dairy cows in Córdoba province, some of which were associated with subclinical mastitis. A culture medium was defined to optimize fumagillin production and a detection method was developed by HPLC chromatography. It is known that in addition to the host immune status, strain virulence is a fundamental characteristic that will determine its pathogenicity and, in this sense, fumagillin is considered to be among the virulence factors. In the present work, all the strains tested for the production of fumagillin were able to synthesize it, highlighting that the strain A. fumigatus RC2243, from a milk sample from a cow with clinical mastitis, was the most productive. The existence of fumagillin-producing strains represents a potential risk of mycotoxins being transferred to raw milk, constituting a public health risk.


Assuntos
Mastite Bovina , Micotoxinas , Animais , Argentina , Aspergillus fumigatus/química , Bovinos , Cicloexanos , Ácidos Graxos Insaturados , Feminino , Humanos , Leite , Sesquiterpenos , Fatores de Virulência
3.
Rev Endocr Metab Disord ; 22(1): 59-70, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33047268

RESUMO

The Ecuadorian cohort of subjects with LS has taught us valuable lessons since the late 80's. We have learned about migration of Sephardic Jews to our country, their isolation in remote hamlets and further inbreeding. These geographical, historical and social determinants induced dissemination of a growth hormone (GH) receptor mutation which widely occurred in those almost inaccessible villages. Consequently, the world's largest Laron syndrome (LS) cohort emerged in Loja and El Oro, two of the southern provinces of Ecuador. We have been fortunate to study these patients since 1987. New clinical features derived from GH insensitivity, their growth patterns as well as treatment with exogenous insulin-like growth factor I (IGF-I) have been reported. Novel biochemical characteristics in the field of GH insensitivity, IGFs, IGF binding proteins (BP) and their clinical correlates have also been described. In the last few years, studies on the morbidity and mortality of Ecuadorian LS adults surprisingly demonstrated that despite obesity, they had lower incidence of diabetes and cancer than their relatives. These events were linked to their metabolic phenotype of elevated but ineffective GH concentrations and low circulating IGF-I and IGFBP-3. It was also noted that absent GH counter-regulation induces a decrease in insulin resistance (IR), which results in low but highly efficient insulin levels which properly handle metabolic substrates. We propose that the combination of low IGF-I signaling, decreased IR, and efficient serum insulin concentrations are reasonable explanations for the diminished incidence of diabetes and cancer in these subjects.


Assuntos
Síndrome de Laron , Equador/epidemiologia , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Síndrome de Laron/epidemiologia , Síndrome de Laron/genética , Fenótipo , Receptores da Somatotropina/genética
4.
BMC Biotechnol ; 19(1): 42, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253149

RESUMO

BACKGROUND: Artificial Mitochondrial Transfer or Transplant (AMT/T) can be used to reduce the stress and loss of viability of damaged cells. In MitoCeption, a type of AMT/T, the isolated mitochondria and recipient cells are centrifuged together at 4 °C and then co-incubated at 37 °C in normal culture conditions, inducing the transfer. Ultraviolet radiation (UVR) can affect mitochondria and other cell structures, resulting in tissue stress, aging, and immunosuppression. AMT/T could be used to repair UVR cellular and mitochondrial damage. We studied if a mitochondrial mix from different donors (Primary Allogeneic Mitochondrial Mix, PAMM) can repair UVR damage and promote cell survival. RESULTS: Using a simplified adaption of the MitoCeption protocol, we used peripheral blood mononuclear cells (PBMCs) as the recipient cell model of the PAMM in order to determine if this protocol could repair UVR damage. Our results showed that when PBMCs are exposed to UVR, there is a decrease in metabolic activity, mitochondrial mass, and mtDNA sequence stability as well as an increase in p53 expression and the percentage of dead cells. When PAMM MitoCeption was used on UVR-damaged cells, it successfully transferred mitochondria from different donors to distinct PBMCs populations and repaired the observed UVR damage. CONCLUSION: Our results represent an advancement in the applications of MitoCeption and other AMT/T. We showed that PBMCs could be used as a PAMM source of mitochondria. We also showed that these mitochondria can be transferred in a mix from different donors (PAMM) to UVR-damaged, non-adherent primary cells. Additionally, we decreased the duration of the MitoCeption protocol.


Assuntos
Dano ao DNA , Leucócitos Mononucleares/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/transplante , Raios Ultravioleta , Adulto , Sobrevivência Celular/genética , Células Cultivadas , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/efeitos da radiação , Masculino , Mitocôndrias/genética , Espécies Reativas de Oxigênio/metabolismo , Transplante Homólogo/métodos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
5.
J Sci Food Agric ; 99(1): 47-54, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29797405

RESUMO

BACKGROUND: A survey on Fusarium species and moniliformin (MON) occurrence in sorghum grains collected from one of the main sorghum-producing areas of Argentina was conducted. Also, growth of F. thapsinum, one of the main sorghum pathogens, and MON production under different water activity (aw ) conditions on a sorghum-based medium were determined. RESULTS: Infection of sorghum grains by Fusarium species ranged from 82.5 to 99%; closely related species F. verticillioides, F. thapsinum and F. andiyazi were the most frequently recovered, followed by F. proliferatum and F. subglutinans. By sequencing a portion of the translation elongation factor-1α (TEF-1α) gene and by maximum parsimony analysis, F. verticillioides and closely related species were identified as F. thapsinum, F. andiyazi and F. verticillioides. Species within the F. graminearum species complex (FGSC) were isolated in high frequency. Maximum growth rates of 12 F. thapsinum strains were obtained at 0.995 aw . All evaluated strains were able to produce MON at all aw values tested, but MON production was higher at 0.995-0.982 aw . MON was detected in 41% of the samples at levels ranging from 363.2 to 914.2 µg kg-1 . CONCLUSION: This study provides new data on the occurrence of Fusarium species in sorghum grains destined for animal consumption in Argentina. The production of MON at different aw values showed that the toxin can be produced under field conditions. The risk to livestock exposed to daily low levels of MON associated with the toxin occurrence in the sorghum grains analyzed is unknown. © 2018 Society of Chemical Industry.


Assuntos
Ração Animal/análise , Ciclobutanos/análise , Fusarium/isolamento & purificação , Micotoxinas/análise , Sorghum/microbiologia , Argentina , Ciclobutanos/metabolismo , Contaminação de Alimentos/análise , Fusarium/classificação , Fusarium/genética , Fusarium/crescimento & desenvolvimento , Micotoxinas/metabolismo , Filogenia , Doenças das Plantas/microbiologia , Sementes/química , Sementes/microbiologia , Sorghum/química
6.
J Health Commun ; 23(3): 299-305, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29474124

RESUMO

This study describes the use of the Internet for health information research by patients attending a gynecologic oncology practice and examines the association between its use and anxiety. A self-administered survey assessed patients' demographic information and Internet use. The Hospital Anxiety and Depression Scale (HADS) and the State-Trait Anxiety Inventory (STAI) were administered concurrently. Of 212 patients who consented to the study, 98 (46%) had an appointment because of a cancer diagnosis. Of 199 respondents, 91 (46%) reported searching the Internet for information about their condition. Internet searching was unassociated with race/ethnicity and positively associated with education level, annual household income, and married/partnered civil status. Only 16% of the patients reported that a health-care provider recommended use of the Internet for research. Comparing patients who used the Internet for research with those who did not, the STAI state and trait anxiety scores were similar. The HADS anxiety subscale score was higher for those who used the Internet versus those who did not, which suggests heightened anxiety. Internet use for research is common in gynecologic oncology patients, and its use is associated with increased anxiety. Physicians can use this medium to educate patients about their disease, build trust, and alleviate fear.


Assuntos
Ansiedade/diagnóstico , Informação de Saúde ao Consumidor/estatística & dados numéricos , Neoplasias dos Genitais Femininos/terapia , Comportamento de Busca de Informação , Internet/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias dos Genitais Femininos/psicologia , Humanos , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Adulto Jovem
7.
Med Mycol ; 53(7): 699-708, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26129892

RESUMO

Aspergillus fumigatus, the major etiological agent of human and animal aspergillosis, is a toxigenic fungus largely regarded as a single species by macroscopic and microscopic features. However, molecular studies have demonstrated that several morphologically identified A. fumigatus strains might be genetically distinct. This work was aimed to apply PCR-restriction length fragment polymorphisms (PCR-RFLP) and random amplification of polymorphic DNA (RAPD) molecular markers to characterize a set of feed-borne and clinical A. fumigatus sensu lato strains isolated from Argentina and Brazil and to determine and compare their genetic variability. All A. fumigatus strains had the same band profile and those typical of A. fumigatus sensu stricto positive controls by PCR-RFLP. Moreover, all Argentinian and Brazilian strains typified by RAPD showed similar band patterns to each other and to A. fumigatus sensu stricto reference strains regardless of their isolation source (animal feeds or human/animal clinical cases) and geographic origin. Genetic similarity coefficients ranged from 0.61 to 1.00, but almost all isolates showed 78% of genetic similarly suggesting that genetic variability was found at intraspecific level. Finally, benA sequencing confirmed its identification as A. fumigatus sensu stricto species. These results suggest that A. fumigatus sensu stricto is a predominant species into Aspergillus section Fumigati found in animal environments as well as in human/animal clinical cases, while other species may be rarely isolated. The strains involved in human and animal aspergillosis could come from the environment where this fungus is frequently found. Rural workers and animals would be constantly exposed.


Assuntos
Aspergilose/microbiologia , Aspergilose/veterinária , Aspergillus fumigatus/classificação , Aspergillus fumigatus/isolamento & purificação , Impressões Digitais de DNA , Microbiologia de Alimentos , Variação Genética , Animais , Argentina/epidemiologia , Aspergilose/epidemiologia , Brasil/epidemiologia , Análise por Conglomerados , Genótipo , Humanos , Epidemiologia Molecular , Dados de Sequência Molecular , Tipagem Molecular , Técnicas de Tipagem Micológica , Filogeografia , Polimorfismo de Fragmento de Restrição , Técnica de Amplificação ao Acaso de DNA Polimórfico , Análise de Sequência de DNA
8.
Med ; 5(7): 816-825.e4, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38677286

RESUMO

BACKGROUND: Human subjects with generalized growth hormone (GH) insensitivity due to GH receptor deficiency (GHRD)/Laron syndrome display a very low incidence of insulin resistance, diabetes, and cancer, as well as delayed age-related cognitive decline. However, the risk of cardiovascular disease (CVD) in these subjects is poorly understood. Here, we have assessed cardiovascular function, damage, and risk factors in GHRD subjects and their relatives. METHODS: We measured markers of CVD in two phases: one in a cohort of 30 individuals (GHRD = 16, control relatives = 14) brought to USC (in Los Angeles, CA) and one in a cohort including additional individuals examined in Ecuador (where the subjects live) for a total of 44 individuals (GHRD = 21, control relatives = 23). Data were collected on GHRD and control groups living in similar geographical locations and sharing comparable environmental and socio-economic circumstances. RESULTS: Compared to controls, GHRD subjects displayed lower serum glucose, insulin, blood pressure, smaller cardiac dimensions, similar pulse wave velocity, lower carotid artery intima-media thickness, lower creatinine, and a non-significant but major reduction in the portion of subjects with carotid atherosclerotic plaques (7% GHRDs vs. 36%, Controls p = 0.1333) despite elevated low-density lipoprotein cholesterol levels. CONCLUSION: The current study indicates that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors as compared to their relatives. FUNDING: This study was funded in part by NIH/NIA grant P01 AG034906 to V.D.L.


Assuntos
Doenças Cardiovasculares , Fatores de Risco de Doenças Cardíacas , Síndrome de Laron , Humanos , Masculino , Feminino , Adulto , Doenças Cardiovasculares/epidemiologia , Síndrome de Laron/genética , Pessoa de Meia-Idade , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/deficiência , Espessura Intima-Media Carotídea , Equador/epidemiologia , Receptores da Somatotropina/genética , Receptores da Somatotropina/deficiência , Análise de Onda de Pulso , Fatores de Risco , Glicemia/metabolismo , Glicemia/análise , Pressão Sanguínea , Estudos de Casos e Controles
9.
Trauma Violence Abuse ; 25(4): 3037-3053, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38433383

RESUMO

This systematic review addressed the issue of the abuse and neglect of older women (age 60 and over) in rural and remote areas, examining these phenomena's prevalence, risk and protective factors, consequences, and associated perceptions. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Arksey and O'Malley methodological framework, peer-reviewed articles published until September 2023 were identified in six electronic databases. Out of the manuscripts initially identified (n = 219), 28 articles met the selection criteria. The study's quality was assessed using the Mixed Methods Appraisal Tool. The included studies provided a comprehensive overview of this phenomenon, encompassing data from 6,579 older rural women. Prevalence rates of abuse and neglect exhibited wide variability, with an average of 27.3%. Among the risk factors, financial dependence and incapacity stood out, while higher income and education levels were protective factors, among others. Emotional/psychological abuse emerged as the most common form, with significant impacts on older women's physical and mental health. Cultural norms and gender expectations also influenced perceptions of abuse and victims' coping mechanisms. In a context in which access to specialized resources and services is hampered by significant limitations, community awareness and education prove vital to address this issue, which positions social work as key to addressing these challenges. The prevalence of abuse against older rural women is significant. Emotional abuse stands out as a major issue, underscoring the need for comprehensive interventions accounting for cultural and gender factors.


Assuntos
Abuso de Idosos , População Rural , Humanos , Feminino , População Rural/estatística & dados numéricos , Abuso de Idosos/estatística & dados numéricos , Abuso de Idosos/psicologia , Prevalência , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Idoso de 80 Anos ou mais
10.
Neurodegener Dis ; 11(4): 165-81, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22796753

RESUMO

BACKGROUND: We aimed to investigate the influence of oligomeric forms of ß-amyloid (Aß) and the influence of the duration of exposure on the development of tau phosphorylation. METHODS: Aß oligomers were injected intracranially either acutely into 5-month-old rTg4510 mice and tissue was collected 3 days later, or chronically into 3-month-old mice and tissue was collected 2 months later. Several forms of phosphorylated tau (p-tau), GSK3 (glycogen synthase kinase-3) and microglial and astrocyte activation were measured. RESULTS: Acute injections of Aß oligomers had no effect on p-tau epitopes but did result in elevation of phosphorylated/activated GSK3 (pGSK3). Chronic infusion of Aß oligomers into the right hippocampus resulted in 3- to 4-fold elevations in several p-tau isoforms with no changes in total tau levels. A significant elevation in pGSK3 accompanied these changes. Microglial staining with CD68 paralleled the increase in tau phosphorylation, however, CD45 staining was unaffected by Aß. Control experiments revealed that the infusion of Aß from the minipumps was largely complete by 10 days after implantation. Thus, the elevation in p-tau 2 months after implantation implies that the changes are quite persistent. CONCLUSION: Soluble Aß(1-42) oligomers have long-lasting effects on tau phosphorylation in the rTg4510 model, possibly due to elevations in GSK3. These data suggest that even brief elevations in Aß production, may have enduring impact on the risk for tauopathy.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Hipocampo/efeitos dos fármacos , Microglia/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Tauopatias/patologia , Proteínas tau/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Modelos Animais de Doenças , Quinase 3 da Glicogênio Sintase/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Antígenos Comuns de Leucócito/metabolismo , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Tauopatias/metabolismo
11.
Cardiol Young ; 23(5): 675-81, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23402338

RESUMO

OBJECTIVES: Foetal aortic valvuloplasty has been proposed as a strategy to improve left heart growth and function in foetuses with severe aortic stenosis at risk of progression to hypoplastic left heart syndrome. We report our experience with this intervention. METHODS AND RESULTS: Between 2005 and 2010, five foetuses with aortic stenosis and at risk of progression to hypoplastic left heart syndrome underwent ultrasound-guided percutaneous foetal aortic valvuloplasty. There were no associated maternal complications or foetal demise. In one case, the pregnancy was terminated a couple of weeks after the intervention, one foetus evolved to hypoplastic left heart syndrome, and three did not. CONCLUSIONS: Foetal aortic valvuloplasty seems to be a safe and feasible procedure. It has been reported that it has the potential to prevent progression to hypoplastic left heart syndrome in selected foetuses with severe aortic stenosis. Further investigation regarding physiological and clinical aspects of this disease both prenatally and postnatally will probably allow to improve therapeutic strategies and clinical outcome.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valvuloplastia com Balão/métodos , Coração Fetal/cirurgia , Síndrome do Coração Esquerdo Hipoplásico/prevenção & controle , Adulto , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Procedimentos Cirúrgicos Cardíacos , Estudos de Coortes , Estudos de Viabilidade , Feminino , Coração Fetal/diagnóstico por imagem , Idade Gestacional , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/etiologia , Gravidez , Cirurgia Assistida por Computador , Resultado do Tratamento , Ultrassonografia Pré-Natal , Adulto Jovem
12.
Endocr Relat Cancer ; 30(10)2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37428642

RESUMO

The relationship between growth hormone (GH) excess and cancer is a controversial matter. Until 2016, most studies in patients with acromegaly found links with colon and thyroid neoplasms. However, recent studies found increased risks in gastric, breast, and urinary tract cancer also. Concordantly, clinical situations where GH and insulin-like growth facto-I deficits exist are indeed associated with diminished malignancy incidence. In line with these observations, gain-of-function mutations of various enzymes belonging to the GH and IGF-I signaling pathways have been associated with increased carcinogenesis; similarly, loss-of-function mutations of other enzymes that usually work as tumor repressors are also associated with augmented cancer risk. In a study performed in Ecuador, it was demonstrated that subjects in the Ecuadorian cohort with Laron syndrome (ELS), who have a mutant GH receptor and greatly diminished GH and IGF-I signaling, display diminished incidence of cancer. Along with absent action of GH and IGF-I, ELS individuals also have low serum insulin levels and decreased insulin resistance. Furthermore, hyperglycemia and hyperinsulinemia are indispensable for fast cell mitosis, including that of those cells present in the benign and malignant neoplasms. Notably, and despite their obesity, subjects with the ELS display normoglycemia and hypo-insulinemia, along with diminished incidence of malignancies. We believe that the dual low-IGF-I/low insulin serum levels are responsible for the cancer protection, especially considering that the insulin/INSR signaling is a central site for energy generation in the form of ATP and GDP, which are indispensable for all and every GH/IGF-I physiologic as well as pathologic events.


Assuntos
Acromegalia , Hormônio do Crescimento Humano , Neoplasias , Humanos , Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Insulina
13.
Endocr Relat Cancer ; 30(6)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36971780

RESUMO

Meta-analyses from 2018-2022 have shown that obesity increases the risk of various cancers such as acute myeloid lymphoma, chronic myeloid lymphoma, diffuse beta cell lymphoma, Hodgkin's lymphoma, leukemia, multiple myeloma, non-Hodgkin's lymphoma, bladder, breast, cholangiocarcinoma, colorectal, ovarian, esophageal, kidney, liver, prostate, thyroid, and uterus. Contextually, obesity, and its comorbidities, is the largest, most lethal pandemics in the history of mankind; hence, identification of underlying mechanisms is needed to adequately address this global health threat. Herein, we present the metabolic and hormonal mechanisms linked to obesity that might etiologically contribute to neoplasia, including hyperinsulinemia and putative places in the insulin-signaling pathway. Excess insulin, acting as a growth factor, might contribute to tumorigenesis, while abundant ATP and GDP supply the additional energy needed for proliferation of rapidly dividing cells. Our observations in the Ecuadorian cohort of subjects with Laron syndrome (ELS) prove that obesity does not always associate with increased cancer risk. Indeed, despite excess body fat from birth to death, these individuals display a diminished incidence of cancer when compared to their age- and sex-matched relatives. Furthermore, in cell cultures exposed to potent oxidizing agents, addition of ELS serum induces less DNA damage as well as increased apoptosis. ELS individuals have absent growth hormone (GH) counter-regulatory effects in carbohydrate metabolism due to a defective GH receptor. The corresponding biochemical phenotype includes extremely low basal serum concentrations of insulin and insulin-like growth factor-I, lower basal glucose and triglyceride (TG) levels, and diminished glucose, TG, and insulin responses to orally administered glucose or to a mixed meal.


Assuntos
Síndrome de Laron , Neoplasias , Masculino , Feminino , Humanos , Síndrome de Laron/genética , Equador , Fator de Crescimento Insulin-Like I , Insulina , Neoplasias/epidemiologia , Neoplasias/complicações , Obesidade/epidemiologia , Obesidade/complicações , Glucose
14.
Pediatrics ; 151(Suppl 2)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37125885

RESUMO

OBJECTIVES: In 2019, >71 million children aged <5 had spent their entire lives in conflict-affected settings. Compounding adversities including violence, poverty, and displacement have immediate and long-term effects on early childhood development, health, behavior, and well-being. In response, adaptations of Reach Up have been implemented in conflict and crisis settings. METHODS: This article uses exploratory multiple case study methodology, drawing from implementation and qualitative data from 3 interventions: a mobile phone-based intervention promoting nurturing care among Rohingya and crisis-affected host communities in Bangladesh; Reach Up amid acute violence and displacement in Northeast Syria; and Reach Up group sessions and home visits integrated with health services for an indigenous population in Venezuela. RESULTS: In Bangladesh, tailoring interactive voice response messages improved responsiveness to the developmental needs of young children, yet complementary in-person services were identified as a key program enhancement. In Syria, rapid adaptations of Reach Up addressed the needs of families in acute crisis, including social-emotional learning games for school-aged children. In Venezuela, Reach Up, coupled with complementary lactation counseling, yielded high rates of uptake and satisfaction, and children's language development was highlighted as a key area of growth. CONCLUSIONS: Recommendations to promote early childhood development in crisis and conflict settings include: (1) cultural adaptation based on a holistic understanding of children and caregivers' needs; (2) the integration of child and family safety and linkages with complementary services on the basis of community needs and priorities, and (3) the importance of designing for scale through blended models and costing analyses.


Assuntos
Desenvolvimento Infantil , Aprendizagem , Criança , Feminino , Pré-Escolar , Humanos , Cuidadores , Bangladesh , Síria
15.
Cureus ; 14(5): e24937, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35706734

RESUMO

Narcolepsy is a chronic and disabling neurological disorder characterized by excessive daytime sleepiness (EDS) and cataplexy. Historically, some medications have demonstrated efficacy in managing EDS and cataplexy symptoms. However, some patients cannot tolerate them, become refractory, or may use concomitant medications that preclude the use due to drug-drug interaction. Therefore, there is a necessity to explore the efficacy of new treatments, such as solriamfetol (JZP-110), a 2019 FDA-approved drug indicated to improve wakefulness in adults with EDS associated with narcolepsy. We conducted this systematic review to investigate the effectiveness of solriamfetol in EDS and cataplexy, and the drug's overall safety. For this study, we used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and MOOSE protocol. After an initial search of 119 papers, we included four clinical trials to investigate and analyze the use of solriamfetol for the treatment of narcolepsy. Solriamfetol was proven to improve objective measures of EDS in all clinical trials. We conducted this systematic review using objective measures such as the Epworth Sleepiness Scale and the Maintenance of Wakefulness Test. Overall, cataplexy was not formally evaluated in the four clinical trials; however, it demonstrated that EDS improved in patients with and without cataplexy. More clinical trials are needed to analyze the efficacy of solriamfetol on cataplexy. The effect of solriamfetol in EDS seems to be conclusive.

16.
Eur J Case Rep Intern Med ; 8(12): 003032, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35059337

RESUMO

Ramsay Hunt syndrome is a rare complication of herpes zoster that results from reactivation of varicella-zoster virus in the geniculate ganglion of the VII cranial nerve. Immunosuppression can lead to reactivation of latent varicella-zoster virus, resulting in herpes zoster. Here, we present a case of Ramsay Hunt syndrome in a patient with ulcerative colitis under treatment with infliximab. LEARNING POINTS: Ramsay Hunt syndrome is a rare form of herpes zoster and characterized by the presence of otalgia, facial palsy, vertigo and vesicular rash in the external ear or on the oropharynx.Treatment with TNF inhibitors increases the risk of its development.Although not generally recommended, vaccination may reduce the risk of herpes zoster recurrence during TNF inhibitor therapy.

17.
Mol Cell Endocrinol ; 519: 111044, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33053393

RESUMO

Human size is achieved by the coordinated expression of many genes. From conception to adulthood, a given genomic endowment is modified by highly variable environmental circumstances. During each stage of a person's life, distinct nutritional and hormonal influences continuously shape growing physical features until mature characteristics are attained. Underlying processes depend on precise provision of substrates and energy extracted by insulin action from nutrients, which allows cell proliferation, differentiation, and survival, under the concerted actions of growth hormone and insulin-like growth factor-I (IGF-I). It should be noted that growth and metabolic signaling pathways are interdependent and superimposed at multiple levels. Attainment of a fully developed human phenotype should be considered as a harmonious increment in body size rather than a simple increase in height. From this perspective we herein analyze adult features of individuals with an inactive growth hormone receptor, who consequently have severely diminished concentrations of serum insulin and endocrine IGF-I.


Assuntos
Transtornos do Crescimento/genética , Perda Auditiva Neurossensorial/genética , Hormônio do Crescimento Humano/genética , Resistência à Insulina/genética , Fator de Crescimento Insulin-Like I/deficiência , Mutação/genética , Crescimento e Desenvolvimento/genética , Humanos , Fator de Crescimento Insulin-Like I/genética , Transdução de Sinais
18.
J Clin Transl Sci ; 4(1): 28-35, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32257408

RESUMO

The National Center for Advancing Translational Sciences has called for more comprehensive research with priority populations to reduce disparities and for the development of additional resources to assist researchers in implementing these recommendations. Here we report the development and initial evaluation of five Priority Populations Toolkits, which are resources developed by the University of Illinois Center for Clinical and Translational Science to meet these goals. Three aims guide the content: increasing knowledge, facilitating communication, and improving research design. Materials were curated from scientific literature reviews and Internet searches and revised iteratively. Analytics and user surveys provide information about usage. In 22 months, 387 unique users accessed the toolkits. The top reason for usage was to improve research recruitment. Comprehensive toolkits for working with priority populations show promising potential for increasing knowledge and readiness to work with underrepresented populations. Further toolkit development and evaluation of effectiveness are warranted.

19.
J Endod ; 46(2): 158-161, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31839411

RESUMO

INTRODUCTION: The aim of this in vivo study was to compare the accuracy of 3 electronic apex locators (EALs) (Root ZX mini [J Morita Corp, Tokyo, Japan], Apex ID [SybronEndo, Glendora, CA], and Propex Pixi [Dentsply Maillefer, Ballaigues, Switzerland]) to determine the working length. METHODS: Thirty single-rooted human teeth that were scheduled for extraction were selected for the study. Electronic measurements were performed with the 3 EALs. After the teeth had been extracted, a #10 K-file was used to determine the actual working length, which was established at 0.5 mm short of the major foramen. The data were statistically analyzed with analysis of variance (α = 0.05). RESULTS: No significant differences were found among the experimental groups (P > .05). The mean distance from the actual working length to the file tip was 0.163 ± 0.032 mm when Root ZX mini was used, 0.343 ± 0.032 mm for Propex Pixi , and 0.012 ± 0.008 mm for Apex ID. CONCLUSIONS: Under the in vivo conditions of this study, no statistically significant differences were observed among the 3 EALs.


Assuntos
Preparo de Canal Radicular , Ápice Dentário , Cavidade Pulpar , Humanos , Odontometria , Raiz Dentária
20.
Sci Rep ; 10(1): 21171, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33273534

RESUMO

We present isotopic and morphometric evidence suggesting the migration of farmers in the southern Andes in the period AD 1270-1420, leading up to the Inka conquest occurring ~ AD 1400. This is based on the interdisciplinary study of human remains from archaeological cemeteries in the Andean Uspallata Valley (Argentina), located in the southern frontier of the Inka Empire. The studied samples span AD 800-1500, encompassing the highly dynamic Late Intermediate Period and culminating with the imperial expansion. Our research combines a macro-regional study of human paleomobility and migration based on a new strontium isoscape across the Andes that allows identifying locals and migrants, a geometric morphometric analysis of cranio-facial morphology suggesting separate ancestral lineages, and a paleodietary reconstruction based on stable isotopes showing that the migrants had diets exceptionally high in C4 plants and largely based on maize agriculture. Significantly, this migration influx occurred during a period of regional demographic increase and would have been part of a widespread period of change in settlement patterns and population movements that preceded the Inka expansion. These processes increased local social diversity and may have been subsequently utilized by the Inka to channel interaction with the local societies.

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