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2.
Mol Biol Rep ; 50(11): 9273-9282, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37812351

RESUMEN

BACKGROUND: As the world's leading fiber crop and a major oil-producing crop, cotton fiber yield and fiber quality are affected by environmental stresses, especially heat, drought and salinity. The LAZ1 (Lazarus 1) family genes are responsive to abscisic acid, drought, and salt treatments. Currently, mining and functional analyses of LAZ1 family genes in cotton have not been reported. METHODS AND RESULTS: In this study, 20 GhLAZ1 genes, designated GhLAZ1-1 - GhLAZ1-20, were identified in the genome of Gossypium hirsutum through the construction of an HMM model, and their molecular properties, chromosomal localization, phylogeny, gene structure, evolutionary selection pressure, promoter cis elements and gene expression under salt stress were analyzed. With the exception of GhLAZ1-17 and GhLAZ1-20, the remaining 18 GhLAZ1 genes were unevenly localized on 13 chromosomes in G. hirsutum; evolutionary analysis showed that these genes could be divided into three subfamilies; and evolutionary selection pressure analysis demonstrated that the GhLAZ1 genes were all under purifying selection. Many elements related to light responses, hormone responses, and abiotic stresses were predicted on the GhLAZ1 family gene promoters, and real-time quantitative PCR results showed that GhLAZ1-2, GhLAZ1-8, and GhLAZ1-18 were upregulated significantly in salt-treated cotton leaves. CONCLUSIONS: Our results suggested that GhLAZ1 genes were involved in the salt tolerance mechanism in G. hirsutum and provided a reference for further exploring the function and molecular mechanism of LAZ1 genes.


Asunto(s)
Gossypium , Familia de Multigenes , Gossypium/genética , Estrés Fisiológico/genética , Regiones Promotoras Genéticas/genética , Ácido Abscísico , Regulación de la Expresión Génica de las Plantas/genética , Filogenia , Proteínas de Plantas/genética
3.
EClinicalMedicine ; 58: 101912, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36969345

RESUMEN

Background: Isoniazid preventive therapy (IPT) initiation during pregnancy was associated with increased incidence of adverse pregnancy outcomes in the TB APPRISE trial. Effects of in utero IPT exposure on infant growth are unknown. Methods: This post-hoc analysis used data from the TB APPRISE trial, a multicentre, double-blind, placebo-controlled trial, which randomised women to 28-week IPT starting in pregnancy (pregnancy-IPT) or postpartum week 12 (postpartum-IPT) in eight countries with high tuberculosis prevalence. Participants were enrolled between August 2014 and April 2016. Based on modified intent-to-treat analyses, we analysed only live-born babies who had at least one follow-up after birth and compared time to infant growth faltering between arms to 12 weeks and 48 weeks postpartum in overall and sex-stratified multivariable Cox proportional hazards regression. Factors adjusted in the final models include sex of infant, mother's baseline BMI, age in years, ART regimen, viral load, CD4 count, education, and household food insecurity. Results: Among 898 HIV-exposed uninfected (HEU) infants, 447 (49.8%) were females. Infants in pregnancy-IPT had a 1.47-fold higher risk of becoming underweight by 12 weeks (aHR 1.47 [95% CI: 1.06, 2.03]) than infants in the postpartum-IPT; increased risk persisted to 48 weeks postpartum (aHR 1.34 [95% CI: 1.01, 1.78]). Maternal IPT timing was not associated with stunting or wasting. In sex-stratified analyses, male infants in the pregnancy-IPT arm experienced an increased risk of low birth weight (LBW) (aRR 2.04 [95% CI: 1.16, 3.68), preterm birth (aRR 1.81 [95% CI: 1.04, 3.21]) and becoming underweight by 12 weeks (aHR 2.02 [95% CI: 1.29, 3.18]) and 48 weeks (aHR 1.82 [95% CI: 1.23, 2.69]). Maternal IPT timing did not influence growth in female infants. Interpretation: Maternal IPT during pregnancy was associated with an increased risk of LBW, preterm birth, and becoming underweight among HEU infants, particularly male infants. These data add to prior TB APPRISE data, suggesting that IPT during pregnancy impacts infant growth, which could inform management, and warrants further examination of mechanisms. Funding: The TB APPRISE study Supported by the National Institutes of Health (NIH) (award numbers, UM1AI068632 [IMPAACT LOC], UM1AI068616 [IMPAACT SDMC], and UM1AI106716 [IMPAACT LC]) through the National Institute of Allergy and Infectious Diseases, with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract number, HHSN275201800001I) and the National Institute of Mental Health.

4.
Orv Hetil ; 164(5): 179-185, 2023 Feb 05.
Artículo en Húngaro | MEDLINE | ID: mdl-36739552

RESUMEN

INTRODUCTION: A wealth of physiological, pathophysiological and clinical evidence of the beneficial effects of childhood fever exists already. Nevertheless, the public perception of fever has become persistently negative. Sociological research attributes this to a number of factors: unjustified fear, help-seeking behaviour, complex behavioural patterns of symptom avoidance and comfort-seeking. One of the keys to this change in attitudes, in the light of recent research, is linked to changes in the awareness and understanding of health among health professionals and lay people. The role of the young generation using media is crucial. OBJECTIVE: To establish a long-term research project to reduce the use of medication (antipyretics and antibiotics) and the number of medical consultations and to improve attitudes towards fever, using media-based e-health tools. METHOD: An observational, adaptive, prospective cohort study was conducted. The intervention under study is a publicly available application and linked knowledge base. We collect self-reported data from caregivers. The application takes these into account and provides a decision-supporting condition classification based on a differential diagnosis algorithm. RESULTS: 1) The parameters, primary and secondary criteria to be captured in the application as well as the data collection and data processing methodology for the assessment were defined by 100% consensus of the expert partners in a Delphi process. 2) Based on the available national and international guidelines, the above parameters were used to create the condition assessment, decision aid algorithm, which can be a starting point for machine learning in the long term. 3) We evaluated baseline data on demographics, febrile events and antipyretic use from 01/11/2020 to 15/06/2022. CONCLUSION: The FeverFriendTM project can contribute to reduce the burden of medicalisation and care burden on the existing healthcare system through evidence-based modern fever management in the care of children and adults with fever. The impact of the FeverFriendTM program on target behavioural change needs to be further investigated through data analysis. Orv Hetil. 2023; 164(5): 179-185.


Asunto(s)
Cuidadores , Fiebre , Niño , Adulto , Humanos , Estudios Prospectivos , Fiebre/tratamiento farmacológico , Personal de Salud , Autoinforme
5.
Orv Hetil ; 163(49): 1935-1942, 2022 Dec 04.
Artículo en Húngaro | MEDLINE | ID: mdl-36463550

RESUMEN

Fever of unknown origin is a common differential diagnostic problem in medicine. More than 60 years have passed since the first established definition of the disease, and despite constant development and improvement of diagnostic procedures, the differential diagnosis and choosing adequate therapy still remains a challenge in this patient population. The medical literature lists at least 200 diseases that may manifest with fever of unknown origin, and it encompasses a wide clinical spectrum. This symptom is present in approximately 1.5-3% of hospitalized patients. In recent decades, not only the concept of fever of unknown origin has changed several times, but the recommended differential diagnostic procedures as well. Positron emission tomography is one of the latest imaging procedures that also contributes to establishing the correct diagnosis. The purpose of this publication is to provide an overview of different diseases which might cause fever of unknown origin, and the most frequently used diagnostic algorithms, moreover to highlight the importance of positron emission tomography in the evaluation of the aetiology of fever of unknown origin. Orv Hetil. 2022; 163(49): 1935-1942.


Asunto(s)
Fiebre de Origen Desconocido , Fluorodesoxiglucosa F18 , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fiebre de Origen Desconocido/diagnóstico por imagen , Fiebre de Origen Desconocido/etiología , Tomografía de Emisión de Positrones , Diagnóstico Diferencial
6.
J Nutr Sci ; 11: e92, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36337985

RESUMEN

Little is known about the relation between the women empowerment in agriculture index, and health and nutrition outcomes among under-five children in Ethiopia. The study's objective was to examine women's empowerment in agriculture and its association with the nutritional status of children (6-59 months) in rural, cash crop producing, and resource-limited settings of Ethiopia. A community-based cross-sectional study was conducted employing 422 households; having women of reproductive age group and children under-five. Stratified simple random sampling was used to identify households; a simple random sampling was used to select villages and households. Women empowerment in agriculture was measured by the abbreviated women empowerment in agriculture index. Even if the overall multi-dimensional five domains of empowerment index (5DE) was not a significant predictor of nutritional status in children (P > 0⋅05), sub-indicators had a pivotal role in child nutritional status. Disempowerment in decisions about input into production [AOR = 8⋅85], empowerment on control of income [AOR = 0⋅35] and availability of livestock [AOR = 0⋅38] were predictors of child stunting, whereas women's disempowerment in production decisions seems beneficiary for wasting, disempowered women have 84 % less likely to have wasted child than empowered women [AOR = 0⋅16]. Dietary and agricultural diversity [particularly livestock farming], and women's empowerment in production decisions were predictors of better nutritional outcomes in children. Therefore, a concentrated effort is needed towards strengthening the multi-dimensional empowerment of women in agriculture emphasising women's input into production decisions, dietary and agricultural diversification, mainly livestock farming.


Asunto(s)
Fenómenos Fisiológicos Nutricionales Infantiles , Estado Nutricional , Niño , Humanos , Femenino , Estudios Transversales , Etiopía , Agricultura
7.
J Nutr Sci ; 10: e44, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34164123

RESUMEN

Childhood undernutrition coupled with poor feeding practices continues to be public health problems in many parts of the world and efforts to address them remain elusive. We tested the hypothesis that women who are exposed to radio health/nutrition education will demonstrate greater nutrition and health knowledge, positive attitudes towards preventive health and better dietary diversity practices for improved child growth. We used a two-arm, quasi-experimental, non-equivalent comparison group design with pre- and post-test observations to evaluate the intervention. The study population comprised 712 mothers with children aged 6-36 months who were randomly selected from five intervention districts and one comparison district in Northern Ghana. Difference-in-difference (DID) analysis was performed to assess study outcomes. After 12-month implementation of intervention activities, the minimum dietary diversity and the minimum acceptable diet improved significantly (DID 9⋅7 percentage points, P 0⋅014 and DID 12⋅1 percentage points, P 0⋅001, respectively) in the intervention study group, compared with the comparison group. Mothers in the intervention communities had a nutrition-related knowledge, attitudes and practices score that was significantly higher than their colleagues in the comparison communities (DID 0⋅646, P < 0⋅001). The intervention did not have significant effects on the nutritional status as measured by height-for-age Z-score or weight-for-height Z-score. The data provide evidence that health and nutrition education using radio drama significantly increased health-/nutrition-related knowledge but had little effect on nutritional status.


Asunto(s)
Comunicación , Conocimientos, Actitudes y Práctica en Salud , Madres , Estado Nutricional , Lactancia Materna , Preescolar , Femenino , Ghana , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Radio
8.
Ophthalmic Genet ; 42(5): 521-532, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33949280

RESUMEN

Background: Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant retinal dystrophy related to C1QTNF5 gene variants.Materials and methods: Twenty-six patients (21-81 years) with L-ORD due to c.562C>A p.(Pro188Thr) with a mean follow-up time of 8 years (range 1-37 years) underwent an extensive ophthalmic work-up.Results: Best-corrected visual acuity (BCVA) and visual fields were maintained up to 50 to 55 years (n = 8), with a gradual decline, but conservation of functional central vision between 55 to 65 years (n = 15), followed by a steep decrease in overall visual function beyond 65 years (n = 9). Classic anterior segment findings in L-ORD of abnormally long, anteriorly inserted lens zonules were absent in most patients (n = 24/26). In contrast, findings of iris transillumination and sphincter pupillae atrophy with poor dilation were novel. Patients presented with three completely different initial fundus phenotypes: adjoining pavingstone-like atrophic patches (type 1) (n = 6/20); tiny yellow-white subretinal dots (type 2) (n = 8/20); or larger yellow, thick, round sub-RPE drusenoid deposits (type 3) (n = 4/20). Two patients had a mixed phenotype. Although different in presentation phenotype, patients eventually all progressed to a common panretinal atrophy with diffuse intraretinal pigment migration beyond the age of 65. Progression pace, and thus visual prognosis, differed depending on presentation phenotype. Specifically, type 2 appears to have a more benign course.Conclusions: Phenotypic analysis showed three distinct presenting phenotypes with a considerable intrafamilial variability both in age of onset of clinical signs and in disease progression, with a fair visual potential (>20/40) until the seventh decade.Abbreviations: L-ORD: Late-onset retinal degeneration; C1QTNF5: complement 1Q tumor necrosis factor 5; OCT: Ocular coherence tomography; BCVA: Best-corrected visual acuity; RPE: Retinal pigment epithelium; ffERG: Full-field electroretinography; IRD: Inherited retinal dystrophy; CNV: Choroidal neovascularization; LAZ: Long anteriorly inserted zonules; AMPK: AMP-activated protein kinase; IOP: Intraocular pressure; cSLO: confocal scanning laser ophthalmoscopy; BAF: Blue light autofluorescence; NIR-AF: Near-infrared autofluorescence; NIR-R: Near-infrared reflectance; RF: Red-free; SD-OCT: Spectral domain ocular coherence tomography; HRR: Hardy-Rand-Rittler pseudo-isochromatic plates; AS: anterior segment; UBM: ultrasound biomicroscopy; PCR: Polymerase chain reaction; SNP: Single nucleotide polymorphism; VEGF: Vascular endothelial growth factor; IZ: Interdigitation zone; EZ: Ellipsoid zone; ELM: External limiting membrane; LP: Light perception; AMD: Age-related macular degeneration; SFD: Sorsby fundus dystrophy.


Asunto(s)
Colágeno/genética , Efecto Fundador , Polimorfismo de Nucleótido Simple , Degeneración Retiniana/genética , Adulto , Anciano , Anciano de 80 o más Años , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Degeneración Retiniana/diagnóstico , Degeneración Retiniana/fisiopatología , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Campos Visuales/fisiología , Adulto Joven
9.
Orv Hetil ; 160(51): 2026-2035, 2019 Dec.
Artículo en Húngaro | MEDLINE | ID: mdl-31838862

RESUMEN

Introduction: According to the European Centre for Disease Prevention and Control, the prevalence of neuroinvasive symptoms caused by the West Nile virus (WNV) has significantly increased in the past years throughout Europe, including Hungary. The rise may be attributed to changes in precipitation and climate. The WNV zoonosis is spread by mosquitoes. It is mostly asymptomatic, flu-like symptoms occur in 20% of the cases and in less than 1% a neuroinvasive disease with a lethal outcome may develop. Aim: Our aim was to demonstrate the neuroinvasive symptomatology and the diagnosis and treatment of WNV infections by describing our patient cases as well as to resolve differential diagnostic dilemmas. Method: We report the cases of 4 patients treated at the "Moritz Kaposi" Somogy County Hospital between the 31st July and 4th September, 2018, with WNV, whose diagnoses were confirmed by serological and molecular biological methods. An epidemiological overview of WNV infections was also given. Results: Four patients were confirmed to have had WNV infection in the given time period. A wide range of neurological symptoms were observed in each patient and death occurred in one case. The patients were elderly with a number of comorbidities. Conclusions: The appearance of more severe, neuroinvasive symptoms following WNV infections is also characteristic of Hungary. The treatment of the infection is supportive, including giving pain relievers and the management of secondary infections. It is important to consider the possibility of a WNV infection in the case of a neurological disease of unknown origin, particularly if the symptoms indicate encephalitis. Orv Hetil. 2019; 160(51): 2026-2035.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Encefalitis Viral/epidemiología , Fiebre del Nilo Occidental/diagnóstico , Virus del Nilo Occidental/aislamiento & purificación , Anciano , Animales , Anticuerpos Antivirales/sangre , Humanos , Hungría/epidemiología , Prevalencia , Fiebre del Nilo Occidental/epidemiología
10.
J Nutr Sci ; 8: e22, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31275576

RESUMEN

Inadequate protein quality may be a risk factor for poor growth. To examine the effect of a macronutrient-micronutrient supplement KOKO Plus (KP), provided to infants from 6 to 18 months of age, on linear growth, a single-blind cluster-randomised study was implemented in Ghana. A total of thirty-eight communities were randomly allocated to receive KP (fourteen communities, n 322), a micronutrient powder (MN, thirteen communities, n 329) and nutrition education (NE, eleven communities, n 319). A comparison group was followed cross-sectionally (n 303). Supplement delivery and morbidity were measured weekly and anthropometry monthly. NE education was provided monthly. Baseline, midline and endline measurements at 6, 12 and 18 months included venous blood draws, diet, anthropometry, morbidity, food security and socio-economics. Length-for-age Z-score (LAZ) was the primary outcome. Analyses were intent-to-treat using mixed-effects regressions adjusted for clustering, sex, age and baseline. No differences existed in mean LAZ scores at endline (-1·219 (sd 0·06) KP, -1·211 (sd 0·03) MN, -1·266 (sd 0·03) NE). Acute infection prevalence was lower in the KP than NE group (P = 0·043). Mean serum Hb was higher in KP infants free from acute infection (114·02 (sd 1·87) g/l) than MN (107·8 (sd 2·5) g/l; P = 0·047) and NE (108·8 (sd 0·99) g/l; P = 0·051). Compliance was 84·9 % (KP) and 87·2 % (MN) but delivery 60 %. Adjusting for delivery and compliance, LAZ score at endline was significantly higher in the KP v. MN group (+0·2 LAZ; P = 0·026). A macro- and micronutrient-fortified supplement KP reduced acute infection, improved Hb and demonstrated a dose-response effect on LAZ adjusting consumption for delivery.


Asunto(s)
Control de Enfermedades Transmisibles , Suplementos Dietéticos , Alimentos Fortificados , Hemoglobinas , Micronutrientes/uso terapéutico , Antropometría , Biomarcadores , Enfermedades Transmisibles , Femenino , Abastecimiento de Alimentos , Ghana , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Inflamación , Masculino , Morbilidad , Prevalencia , Factores de Riesgo , Método Simple Ciego , Factores Socioeconómicos , Encuestas y Cuestionarios , Resultado del Tratamiento
11.
Br J Nutr ; 121(6): 688-698, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30670108

RESUMEN

The study aimed at assessing stunting, wasting and breast-feeding as correlates of body composition in Cambodian children. As part of a nutrition trial (ISRCTN19918531), fat mass (FM) and fat-free mass (FFM) were measured using 2H dilution at 6 and 15 months of age. Of 419 infants enrolled, 98 % were breastfed, 15 % stunted and 4 % wasted at 6 months. At 15 months, 78 % were breastfed, 24 % stunted and 11 % wasted. Those not breastfed had lower FMI at 6 months but not at 15 months. Stunted children had lower FM at 6 months and lower FFM at 6 and 15 months compared with children with length-for-age z ≥0. Stunting was not associated with height-adjusted indexes fat mass index (FMI) or fat-free mass index (FFMI). Wasted children had lower FM, FFM, FMI and FFMI at 6 and 15 months compared with children with weight-for-length z (WLZ) ≥0. Generally, FFM and FFMI deficits increased with age, whereas FM and FMI deficits decreased, reflecting interactions between age and WLZ. For example, the FFM deficits were -0·99 (95 % CI -1·26, -0·72) kg at 6 months and -1·44 (95 % CI -1·69; -1·19) kg at 15 months (interaction, P<0·05), while the FMI deficits were -2·12 (95 % CI -2·53, -1·72) kg/m2 at 6 months and -1·32 (95 % CI -1·77, -0·87) kg/m2 at 15 months (interaction, P<0·05). This indicates that undernourished children preserve body fat at the detriment of fat-free tissue, which may have long-term consequences for health and working capacity.


Asunto(s)
Composición Corporal , Lactancia Materna , Trastornos del Crecimiento/fisiopatología , Fenómenos Fisiológicos Nutricionales del Lactante , Síndrome Debilitante/fisiopatología , Tejido Adiposo , Índice de Masa Corporal , Cambodia , Femenino , Trastornos del Crecimiento/etiología , Humanos , Lactante , Masculino , Estado Nutricional , Síndrome Debilitante/etiología
12.
Matern Child Nutr ; 15(3): e12776, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30609287

RESUMEN

HIV-exposed and HIV-uninfected (HEU) infants may be at increased risk of poor health and growth outcomes. We characterized infant growth trajectories in a cohort of HEU infants to identify factors associated with healthy growth. HIV-positive women participating in prevention of mother-to-child HIV transmission programmes in Kigali, Rwanda, were followed until their infants were 2 years old. Infant anthropometrics were regularly collected. Latent class analysis was used to categorize infant growth trajectories. Multiple logistic regression was used to estimate the odds of infants belonging to each growth trajectory class. On average, this population of HEU infants had moderate linear growth faltering, but only modest faltering in weight, resulting in mean weight-for-length z-score (WLZ) above the World Health Organization (WHO) median. Mean WLZ was 0.53, and mean length-for-age z-score (LAZ) was -1.14 over the first 2 years of life. We identified four unique WLZ trajectories and seven trajectories in LAZ. Low neonatal weight-for-age and a high rate of illness increased the likelihood that infants were in the lightest WLZ class. Shorter mothers were more likely to have infants with linear growth faltering. Female infants who were older at the end of exclusive breastfeeding were more likely to be in the second tallest LAZ class. In conclusion, the current WHO recommendations of Option B+ and extended breastfeeding may induce higher WLZ and lower LAZ early in infancy. However, there is considerable heterogeneity in growth patterns that is obscured by simply analysing average growth trends, necessitating the analysis of growth in subpopulations.


Asunto(s)
Desarrollo Infantil/fisiología , Infecciones por VIH/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Estatura/fisiología , Peso Corporal/fisiología , Lactancia Materna/estadística & datos numéricos , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Rwanda
13.
Front Microbiol ; 9: 2915, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30538694

RESUMEN

Lipid-modified cupredoxin azurin (Laz) is involved in electron transport in Neisseria and proposed to act as an electron donor to the surface-displayed nitrite reductase AniA. We identified Laz in Neisseria gonorrhoeae cell envelopes and naturally elaborated membrane vesicles in proteomic investigations focused on discovering new vaccine and therapeutic targets for this increasingly difficult to treat pathogen. Its surface exposure in N. meningitidis suggested Laz could be a vaccine candidate for N. gonorrhoeae. Here we characterized the localization, expression, and role of Laz within the gonococcal cell envelope and challenged the hypothesis that Laz and AniA interact. While we demonstrate that Laz indeed shows some good features of a vaccine antigen, such as stable expression, high conservation, and ability to elicit antibodies that cross-react with a diverse panel of Neisseria, it is not a surface-displayed lipoprotein in the gonococcus. This discovery eliminates Laz as a gonorrhea vaccine candidate, further highlighting the necessity of examining homologous protein localization between closely related species. Absence of Laz slightly altered cell envelope integrity but was not associated with growth defects in vitro, including during anoxia, implicating the presence of other electron pathways to AniA. To further dissect the implied AniA-Laz interaction, we utilized biolayer interferometry and optimized and executed chemical cross-linking coupled with immunoblotting to covalently link interacting protein partners in living gonococci. This method, applied for the first time in N. gonorrhoeae research to interrogate protein complexes, was validated by the appearance of the trimer form of AniA, as well as by increased formation of the ß-barrel assembly machinery complex, in the presence of cross-linker. We conclude that Laz is not an electron donor to AniA based on their distinct subcellular localization, discordant expression during infection of the female mouse lower genital tract, and lack of interaction in vivo and in vitro.

14.
Biochim Biophys Acta Mol Basis Dis ; 1864(10): 3322-3338, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30031228

RESUMEN

Diabetes contributes to cardiovascular complications and the pathogenesis of cardiac remodeling that can lead to heart failure. We aimed to evaluate the functional role of LAZ3 in diabetic cardiomyopathy (DCM). Streptozotocin (STZ) was used to induce a diabetic mouse model. Three months after induction, the mice were subjected to retro-orbital venous plexus injection of adeno-associated virus 9 (AAV9) that overexpressed LAZ3. Six weeks after the infection, mouse hearts were removed to assess the degree of cardiac remodeling. LAZ3 was down-regulated in the diabetic mouse hearts and high glucose stimulated cardiomyocytes. Knock-down of LAZ3 in cardiomyocytes with LAZ3 siRNA reduced cell viability, increased the inflammatory response and induced oxidative stress and cell apoptosis. Overexpression of LAZ3 by infection with adeno-associated virus (AAV9)-LAZ3 protected against an inflammatory response, oxidative stress and cell apoptosis in both a high glucose stimulated in vitro study and diabetic mouse hearts. We found that LAZ3 increased the activation of PPARa, which increased PGC-1a activation and subsequently augmented NRF2 expression and nuclear translocation. This outcome was confirmed by NRF2 siRNA and a PPARa activator, since NRF2 siRNA abrogated the protective effects of LAZ3 overexpression, while the PPARa activator reversed the deteriorating phenotype of LAZ3 knock-down in both the in vitro and vivo study. Furthermore, LAZ3 decreased miR-21 expression, which resulted in PPARa activation, NRF2 expression and nuclear translocation. In conclusion, LAZ3 protects against cardiac remodeling in DCM by decreasing miR-21, thus regulating PPARa/NRF2 signaling.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Cardiomiopatías Diabéticas/prevención & control , MicroARNs/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Transducción de Señal , Animales , Células Cultivadas , Dependovirus/genética , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatías Diabéticas/inducido químicamente , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Vectores Genéticos/administración & dosificación , Ratones , Ratones Endogámicos C57BL , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Ratas , Estreptozocina
15.
Orv Hetil ; 159(26): 1079-1083, 2018 Jul.
Artículo en Húngaro | MEDLINE | ID: mdl-29936853

RESUMEN

Originally published in the Hungarian Postgraduate Journal of Gynecology and Obstetrics (2016; 18: 209-2013). Reprint with the contribution and permission of the Professional Publishing Hungary Kft., Budapest. Orv Hetil. 2018; 159(26): 1079-1083.

16.
Orv Hetil ; 159(26): 1055-1064, 2018 Jul.
Artículo en Húngaro | MEDLINE | ID: mdl-29936856

RESUMEN

In this article we examine why Semmelweis's seemingly simple, logical and practical discovery was categorically dismissed by the majority of his contemporaries, and why even many years after his death it was accepted with such reservation. We invoke wherever possible Semmelweis's own words citing from the series of articles appearing in the 'Orvosi Hetilap' [Hungarian Medical Weekly Journal] published in 1858 in Hungary, and also from the German language summary of the Journal published in 1860. We came to the conclusion that although Semmelweis did everything in his power to show the causal relationship between the development of puerperal fever (childbed fever) and some infectious substance on the hands of examining doctors and medical students, this was not convincing enough. The predominant theory at the time held that infection was caused by miasma transmitted in the air and therefore stubbornly precluded any notion of infectious matter physically transmitted on unclean hands. We also concluded that the causal sequence observed by Semmelweis was missing an essential empirical element: visual proof of the infectious agent he correctly postulated as physically transmitted. Visually demonstrating the presence of the infectious agent by means of a microscope would have made his case. This finally did occur but only two years after Semmelweis's death. Had the renowned Hungarian obstetrician realized the significance of taking advantage of the opportunity afforded by Dávid Gruby who was conducting experiments in the same town, a more convincing argument could have been made for his theory. In the 1840s and 1850s, Dávid Gruby was experimenting with various microscopic techniques and their application with success in Vienna before continuing his work in France. Gruby's work, especially that of microscopic observations of tissues, received international acceptance. Therefore, the involvement of Gruby and his work with microscopes to support Semmelweis's observations would most probably have forestalled much of the criticism and rejection his theory was initially awarded (among which perhaps Virchow's rejection proved the most damaging). Had Semmelweis utilized microscopic techniques, he would have been celebrated among the first to discover bacterial pathogens, contributing to the development of the currently predominant germ theory. Failure to utilize the microscope was the root cause leading to the tragedy of Semmelweis's rejection by the medical establishment of the time. Despite the increasing numbers of scientists utilizing the microscope at the University of Pest, offered to corroborate his daims with microscopic observations. Efforts have been made have since been to rehabilitate him as the key figure who not only discovered the method of transmission of infectious disease, but also implemented measures of prevention. Elevating him among the ranks of the ten greatest doctors who ever lived is certainly recognition due, but sadly denied to him in his lifetime. Orv Hetil. 2018; 159(26): 1055-1064.


Asunto(s)
Investigación Biomédica/historia , Higiene de las Manos/historia , Maternidades/historia , Infección Puerperal/historia , Femenino , Historia del Siglo XIX , Humanos , Obstetricia/historia , Embarazo , Infección Puerperal/prevención & control
17.
Orv Hetil ; 159(26): 1041-1054, 2018 Jul.
Artículo en Húngaro | MEDLINE | ID: mdl-29936859

RESUMEN

Semmelweis finally achieved results from his persistent research work. Those being the scientific analysis of clinical statistical data and his animal experiments, which recognized the dreadful disease of puerperal fever and its prevention. "He not only discovered the real cause of puerperal fever but he also created antiseptic prophylaxis, which he introduced in obstetrics and laid the foundations of modern surgery (asepsis). The theory and practice of asepsis stemmed from the discovery of the etiology of puerperal fever and therefore originating from the genius idea of Semmelweis. The discoveries of bacteriology by Lister, Pasteur and Koch only provided a scientific proof of the intuitive statements of Semmelweis." Semmelweis was a pioneer of clinical etiological research whose findings were aggressively disapproved by his colleagues due to earlier medical misunderstandings. Semmelweis is given due respect by posterity as a remuneration, to all the bitterness that he had suffered throughout his life. Semmelweis is considered the savior of mothers and infants. The Hungarian nation is very proud of him as he is one of our models whose oeuvre is acknowledged not only in Hungary but throughout the world. The message of his short, tragic yet effective life is eternal. The figure of Ignác Semmelweis is depicted as a statue and is placed in Chicago among the statues of the most innovative doctors and health care professionals of the world. The statue of Semmelweis is next to the statues of Louis Pasteur and Wilhelm Conrad Röntgen. "Semmelweis reflex" is a new expression which appeared and spread in English speaking countries. The word does not relate to a medical phenomenon but describes a social phenomenon when experts or the whole society automatically rejects discoveries and new recognitions without examination or justification. This phenomenon frequently occurs, even in our times. Orv Hetil. 2018; 159(26): 1041-1054.


Asunto(s)
Docentes Médicos/historia , Obstetricia/historia , Médicos/historia , Femenino , Historia del Siglo XIX , Humanos , Embarazo , Infección Puerperal/historia
18.
Orv Hetil ; 159(26): 1071-1078, 2018 Jul.
Artículo en Húngaro | MEDLINE | ID: mdl-29936858

RESUMEN

Between 1990 and 2007, being the eighth successor leader following Ignác Semmelweis at the university department of obstetrics in Baross Street, what interested me mainly were the following: the lucky coincidences needed for the great discovery, the doctor's hopeless struggles, the circumstances of his death, his five burials and fourfold exhumations, the Hungarianization of his name and the deliberate or unintentional mistakes related to him. In the recollection, my impressions and experiences related to the great predecessor will be reviewed. Orv Hetil. 2018; 159(26): 1071-1078.


Asunto(s)
Liderazgo , Obstetricia/normas , Femenino , Humanos , Embarazo , Infección Puerperal/prevención & control , Facultades de Medicina/normas
19.
Orv Hetil ; 159(26): 1065-1070, 2018 Jul.
Artículo en Húngaro | MEDLINE | ID: mdl-29936855

RESUMEN

Ignác Semmelweis did not publish his discovery in Vienna - i.e., that the puerperal fever may be prevented by careful washing of the hand in chlorine solution (asepsis) - for ten years. The Medical Weekly started its publications edited by Lajos Markusovszky in Pest in 1857. Semmelweis as a professor of theoretical and practical obstetrics at the University of Pest published a study about puerperal fever in the first volume, and Hungarian physicians became familiar with Semmelweis' opinion from this medical journal. Semmelweis was not only an author of the Medical Weekly, but he also edited a supplement of the Medical Weekly entitled Gynaecology and Paediatry. The Medical Weekly published regular accounts of the work of the clinic written by lecturers of Semmelweis and articles describing the most interesting cases of the clinic. Orv Hetil. 2018; 159(26): 1065-1070.


Asunto(s)
Periodismo Médico/historia , Publicaciones Periódicas como Asunto/historia , Docentes Médicos/historia , Femenino , Historia del Siglo XIX , Humanos , Hungría , Embarazo , Infección Puerperal/historia
20.
Orv Hetil ; 159(23): 898-907, 2018 Jun.
Artículo en Húngaro | MEDLINE | ID: mdl-29860887

RESUMEN

Autoinflammatory diseases are disorders of the innate immune system characterized by recurrent systematic inflammation and serious complications. Dysregulation of inflammasome and overproduction of interleukin-1 play a major role in the pathogenesis of autoinflammatory diseases. The diagnosis of these rare conditions rely on recognising the pattern of presentation and differential diagnosis. Manifestations may include fever, rash, serositis (pleuritis and peritonitis), arthritis, meningitis and uveitis. Secondary amyloidosis may complicate longstanding disease. Advances in our understanding of the molecular and pathophysiological basis of the autoinflammatory diseases have resulted in new treatment strategies. Early diagnosis and effective therapy are critical to prevent irreversible organ damage. The purpose of this review is to describe the major clinical, genetic, and therapeutic features of the most common autoinflammatory syndromes. Orv Hetil. 2018; 159(23): 898-907.


Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Inflamación/diagnóstico , Inflamación/terapia , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/terapia , Humanos , Enfermedades Raras
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