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The prevalence of overweight and obesity continues to rise in the population worldwide. Because it is an important predisposing factor for cancer, cardiovascular diseases, diabetes mellitus, and COVID-19, obesity reduces life expectancy. Adipose tissue (AT), the main fat storage organ with endocrine capacity, plays fundamental roles in systemic metabolism and obesity-related diseases. Dysfunctional AT can induce excess or reduced body fat (lipodystrophy). Dido1 is a marker gene for stemness; gene-targeting experiments compromised several functions ranging from cell division to embryonic stem cell differentiation, both in vivo and in vitro. We report that mutant mice lacking the DIDO N terminus show a lean phenotype. This consists of reduced AT and hypolipidemia, even when mice are fed a high-nutrient diet. DIDO mutation caused hypothermia due to lipoatrophy of white adipose tissue (WAT) and dermal fat thinning. Deep sequencing of the epididymal white fat (Epi WAT) transcriptome supported Dido1 control of the cellular lipid metabolic process. We found that, by controlling the expression of transcription factors such as C/EBPα or PPARγ, Dido1 is necessary for adipocyte differentiation, and that restoring their expression reestablished adipogenesis capacity in Dido1 mutants. Our model differs from other lipodystrophic mice and could constitute a new system for the development of therapeutic intervention in obesity.
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Adipogenia , Lipodistrofia , Animais , Camundongos , Adipogenia/genética , Diferenciação Celular , Dieta , Obesidade/genética , SobrepesoRESUMO
This study was conducted to assess the survival of 2 wild Shiga toxin-producing Escherichia coli strains (one serotype O157:H7 and one non-O157:H7) in ewe milk stored at different conditions and to examine the fate of the O157 strain during the manufacture and ripening of a Spanish sheep hard variety of raw milk cheese (Zamorano). The strains were selected among a population of 50 isolates, which we obtained from ewe milk, because of their high resistance to 0.3% lactic acid. Both strains were inoculated (approximately 2 log10 cfu/mL) in raw and heat-treated (low-temperature holding, LTH; 63°C/30 min) ewe milk and stored for 5 d at 6, 8, and 10°C and also according to a simulation approach for assessing the effects of failures in the cold chain. The minimum growth temperature for the O157:H7 strain in LTH and raw ewe milk was 8°C. For the non-O157:H7 strain, the lowest temperature showing bacterial growth in LTH ewe milk was 6°C, but it did not grow at any of the tested conditions in raw milk. It appears that the O157 strain was more susceptible to cold stress but was likely a better competitor than the non-O157 strain against the milk autochthonous microbiota. For manufacture of Zamorano cheese, raw milk was inoculated with approximately 3 log10 cfu/mL, and after 2 mo of ripening at 10 to 12°C, the cheeses showed the expected general characteristics for this variety. The O157:H7 strain increased 0.9 log10 cfu/g after whey drainage and during ripening and storage decreased by 2.9 log10 cfu/g. Nevertheless, its detectable level (estimated at 6.2 cfu/g) after 2 mo of ripening suggests that Zamorano cheese manufactured from raw ewe milk contaminated with E. coli O157:H7 could represent a public health concern.
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Escherichia coli O157 , Escherichia coli Shiga Toxigênica , Animais , Contagem de Colônia Microbiana/veterinária , Feminino , Microbiologia de Alimentos , Leite/microbiologia , Ovinos , TemperaturaRESUMO
BACKGROUND AND AIMS: Plants in dry Mediterranean mountains experience a double climatic stress: at low elevations, high temperatures coincide with water shortage during summer, while at high elevations temperature decreases and water availability increases. Cushion plants often act as nurses by improving the microclimate underneath their canopies, hosting beneficiary species that may reciprocally modify their benefactors' microenvironment. We assess how the nurse cushion plant Arenaria tetraquetra subsp. amabilis adjusts its hydraulic system to face these complex abiotic and biotic constraints. METHODS: We evaluated intra-specific variation and co-ordination of stem xylem anatomy, leaf functional traits and plant architecture in response to elevation, aspect and the presence of beneficiary species in four A. tetraquetra subsp. amabilis populations in the Sierra Nevada mountains, southern Spain. KEY RESULTS: Xylem anatomical and plant architectural traits were the most responsive to environmental conditions, showing the highest mutual co-ordination. Cushions were more compact and had smaller, more isolated conductive vessels in the southern than in the northern aspect, which allow minimization of the negative impacts of more intense drought. Only vessel size, leaf mass per area and terminal branch length varied with elevation. Nurse cushions co-ordinated plant architecture and xylem traits, having higher canopy compactness, fewer leaves per branch and fewer, more isolated vessels than non-nurse cushions, which reflects the negative effects of beneficiary plants on nurse water status. In non-nurse cushions, plant architecture co-ordinated with leaf traits instead. The interacting effects of aspect and elevation on xylem traits showed that stress due to frost at high elevation constrained xylem anatomy in the north, whereas stress due to drought had a parallel effect in the south. CONCLUSIONS: Trait co-ordination was weaker under more demanding environmental conditions, which agrees with the hypothesis that trait independence allows plants to better optimize different functions, probably entailing higher adjustment potential against future environmental changes.
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Árvores , Xilema , Secas , Folhas de Planta , Plantas , ÁguaRESUMO
The species Carissa grandiflora A. DC., commonly called Natal plum, is a shrub native to the coastal region of Natal, South Africa. In southern Spain, Natal plum is used as an ornamental plant due to its beautiful flowers and red ripen fruits. In March 2019 and 2020, we surveyed nine public gardens in the cities of Cadiz and Sanlucar de Barrameda (Andalusia, Spain); and Natal plum fruit showing anthracnose symptoms were observed in six (55% prevalence) of them. Affected fruits showed necrotic and circular lesions with acervuli in the center (Fig. 1a) causing the complete mummification of the fruit (Fig. 1b). Affected fruits were collected from four gardens and disinfested according to Moral et al. (2010). Six fungal isolates were recovered from small (3-4 × 1-2 mm) pieces of the affected fruits in Potato Dextrose Agar (PDA), and hyphal tips from them were transferred to fresh PDA to obtain pure cultures. The six isolates were initially identified as Colletotrichum karstii according to their morphology and the sequences of the ITS1-5.8S-ITS2 (ITS) region (Damm et al. 2012). The six Colletotrichum isolates showed similar colony morphology and their ITS sequences were identical. Overall, C. karstii isolates showed cylindrical and straight conidia that were 12.1 to 14.2 µm long and 4.9 to 5.6 µm wide (n = 50). The aerial mycelia of the fungus varied from grayish-white to dark gray. A multilocus approach was conducted for more precise identification of the Colletotrichum species. For that, ITS, beta-tubulin (TUB2), actin (ACT), partial sequences of the chitin synthase 1 (CHS-1), histone 3 (HIS3), and a 200-bp intron fragment of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of a representative isolate (FITP19001) were amplified and sequenced according to Damm et al. (2012). GenBank Accession Nos. for ITS, TUB2, ACT, CHS-1, HIS3 and GADPH: MT757643, MT759805, MT759806, MT759807, MT759808 and MT759809, respectively. Sequences showed 100% identity with homologous sequences belonging to C. karstii (GenBank taxid:1095194). To test Koch's postulates, 10 unripen and 10 ripen C. grandiflora fruits, harvested from asymptomatic plants, were inoculated. For each group, five fruits were inoculated using a drop of 10 µl of 5 × 104 conidia per ml suspension of C. karstii (FITP19001) and another five fruits were inoculated using a mycelial plug of the same isolate. Inoculated fruits were incubated in a humid chamber at room temperature (19-24ºC) under light for two weeks. Non-inoculated control fruits were treated with sterile water or a PDA plug and incubated under the same conditions. The pathogenicity test was conducted twice. After 10 days, typical anthracnose symptoms developed on both unripen and ripen inoculated fruits, but not on non-inoculated controls. Overall, the severity of anthracnose lesions was higher on ripen fruits than in the unripen fruits. Likewise, the severity of symptoms was higher on the fruits inoculated using a mycelial plug than on those fruits inoculated with a spore suspension. The species C. karstii was reisolated from lesions of all inoculated fruits as described above but not from non-inoculated fruits. The species C. karstii has been described affecting numerous species worldwide (Damm et al., 2012). Previously, C. gloeosporioides was reported causing fruit anthracnose of Natal plum in Florida (Alfieri et al., 1984). To our knowledge, this is the first report of C. karstii causing anthracnose on the fruit of Natal plum in Spain and worldwide.
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A comparative study of the behaviour of left-sided infective endocarditis (left-sided IE) due to Streptococcus agalactiae (GBS) with left-sided IE caused by Staphylococcus aureus (SA). A prospective, multicentre cohort study in eight public hospitals in Spain, from January 1984 to December 2015; comparative analysis and factors associated with mortality. In total, there were 1754 episodes of left-sided IE; 41 (2.3%) caused by GBS vs. 344 (19.6%) due to SA, definitive IE 39 vs. 324 cases, males, 25 vs. 213, respectively. There were no differences in age or comorbidity, and healthcare-associated acquirement was 10% vs. 43%, p 0.001. Transthoracic echocardiogram (TTE) was performed in 95% vs. 96.8% and a transesophageal echocardiogram (TEE) in 61% vs. 56%. Vegetations were detected in 80% and measured > 1 cm in a similar proportion. It affected native valves in 85.4% vs. 82.6% and late prosthetic valve in 14.6% vs. 9.6%. The course was acute in both groups. There were more skin manifestations in SA left-sided IE, 7.3% vs. 32%, p 0.001. Both groups had similar complications, but in SA, there was more renal failure, 24% vs. 45%, p 0.010. Surgical risk and operated patients were similar. Mortality was proportionally higher in the SA group, without significance 29% vs. 43% (150), p 0.09. Heart failure, septic shock and neurological deterioration conditioned mortality: HR 1.96, 1.69 and 1.37 (CI 95% 1.40-2.73; 1.19-2.39 and 0.99-1.88 respectively) and to a lesser degree SA as aetiology agent and age. Left-sided IE caused by GBS is similar in severity to left-sided IE caused by SA.
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Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/patologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/patologia , Streptococcus agalactiae , Idoso , Infecção Hospitalar/epidemiologia , Endocardite Bacteriana/etiologia , Endocardite Bacteriana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/patologia , Staphylococcus aureus , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/mortalidadeRESUMO
INTRODUCTION: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. It is associated to a higher risk of cardiovascular complications, including infective endocarditis (IE). METHODS: Retrospective, observational and single centre study that included all patients with IE diagnosed between 1996 and 2014. An analysis was made of the epidemiological, clinical, microbiological and echocardiographic data, complications during hospital admission, need for surgery, in-hospital mortality, and 1-year follow-up. Cases with endocarditis on prosthetic valves or other locations were excluded, as well as those for which the aortic valve morphology had not been accurately defined. A comparative statistical analysis was performed between BAV and tricuspid (TAV). RESULTS: Of a total of 328 cases with IE, 118 (35.67%) were on aortic valve, with 18 (16.22%) of them being BAV. The BAV cases were younger than TAV (51±19.06 vs. 60.83±15.73 years, P=.021) and they had less comorbidity (Charlson 0.67±0.77 vs. 1.44±1.64, P=.03).). There was a higher tendency of Staphylococcal origin (38.9 vs. 21.5%, P=.137), and 55.6% showed peri-valvular complications (TAV 16.1%, P=.001), in particular, abscesses (38.9 vs.16.1%, P=.047). BAV was the only predictive factor of peri-valvular complications (OR 7.87, 95% CI; 2.38-26.64, P=.001). Patients with BAV had more surgery during their admission (83.3 vs. 44.1%, P=.004), had less in-hospital mortality, with no statistical significance (5.6 vs. 25.8%, P=.069), and 1-year survival was significantly superior (93.8 vs 69.3%, P=.048). CONCLUSIONS: Patients with IE on BAV are young, with low comorbidity. They frequently present with peri-valvular complications and they often require early surgery. Compared to TAV cases, in-hospital mortality is lower and 1-year survival is significantly higher.
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Valva Aórtica/anormalidades , Endocardite/epidemiologia , Doenças das Valvas Cardíacas/epidemiologia , Injúria Renal Aguda/epidemiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Valva Aórtica/diagnóstico por imagem , Doença da Válvula Aórtica Bicúspide , Encefalopatias/epidemiologia , Terapia Combinada , Comorbidade , Suscetibilidade a Doenças , Endocardite/diagnóstico por imagem , Endocardite/tratamento farmacológico , Endocardite/cirurgia , Feminino , Insuficiência Cardíaca/epidemiologia , Doenças das Valvas Cardíacas/diagnóstico por imagem , Implante de Prótese de Valva Cardíaca , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Choque Séptico/epidemiologiaRESUMO
CONTEXT: The stabilization of flurbiprofen loaded poly-É-caprolactone nanoparticles (FB-PÉCL-NPs) for ocular delivery under accurate freeze-drying (FD) process provides the basis for a large-scale production and its commercial development. OBJECTIVE: Optimization of the FD to improve long-term stability of ocular administration's FB-PÉCL-NPs. METHODS: FB-PÉCL-NPs were prepared by solvent displacement method with poloxamer 188 (P188) as stabilizer. Freezing and primary drying (PD) were studied and optimized through freeze-thawing test and FD microscopy. Design of experiments was used to accurate secondary drying (SD) conditions and components concentration. Formulations were selected according to desired physicochemical properties. Furthermore, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to study interactions components. RESULTS: Optimized FB-PÉCL-NPs, stabilized with 3.5% (w/w) P188 and protected with 8% (w/w) poly(ethylene glycol), was submitted to precooling at +10 °C for 1 h, freezing at -50 °C for 4 h, PD at +5 °C and 0.140 mbar for 24 h and a SD at +45 °C during 10 h. These conditions showed 188.4 ± 1.3 nm, 0.087 ± 0.014, 85.5 ± 1.4%, 0.61 ± 0.12%, -16.4 ± 0.1 mV and 325 ± 7 mOsm/kg of average size, polydispersity index, entrapment efficiency, residual moisture, surface charge and osmolality, respectively. It performed a long-term stability >12 months. DSC and XRD spectra confirmed adequate chemical interaction between formulation components and showed a semi-crystalline state after FD. CONCLUSIONS: An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the FD process.
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Flurbiprofeno/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Polímeros/química , Administração Oftálmica , Varredura Diferencial de Calorimetria/métodos , Caproatos/química , Química Farmacêutica/métodos , Crioprotetores/química , Estabilidade de Medicamentos , Liofilização/métodos , Lactonas/química , Tamanho da Partícula , Poloxâmero/química , Polietilenoglicóis/química , Difração de Raios X/métodosRESUMO
The aim of this study was the characterization of a collection of 8 methicillin-resistant Staphylococcus aureus (MRSA) isolates, obtained from samples of fresh cheese (Doble Crema) produced from raw cow milk in small dairies in Colombia. All the isolates harbored the mecA and Panton-Valentine leukocidin (PVL) genes, presented with SCCmec type IV, and belonged to multilocus sequence type 8 and spa type 024. Seven isolates presented 3 closely related pulsed-field gel electrophoresis profiles. Three of them carried the staphylococcal enterotoxin B gene. The isolates were resistant to cefoxitin, oxacillin, penicillin, and ampicillin and susceptible to all non-ß-lactams antibiotics tested, with minimum inhibitory concentration values for oxacillin of 4 to 8mg/L. The isolates belonged to the community-acquired MRSA group, suggesting a human source of contamination. The risk of human infection by MRSA via contaminated foods is considered low, but contaminated food commodities can contribute to the worldwide dissemination of clones of community-acquired MRSA.
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Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Meticilina , Animais , Antibacterianos/farmacologia , Toxinas Bacterianas/genética , Bovinos , Queijo , Colômbia , Feminino , Humanos , Testes de Sensibilidade Microbiana , Leite/efeitos dos fármacos , Infecções Estafilocócicas , Staphylococcus aureus/isolamento & purificaçãoRESUMO
Introduction: Olive cultivation, like other evergreen fruit crops worldwide, is limited by the occurrence of frost episodes in different times of the year, mainly in winter or early spring. Some contradictory results are reported about cultivars' response to frost, which depends on the physiological stage of the tissues (acclimated or not acclimated) when the cold or frost episode occurs. This work aimed to implement a user-friendly and reliable lab method for discerning frost tolerance. Methods: Our methodology considered both detached leaves and potted plantlets. The optimal temperature at which damage differentiated between cultivars was evaluated, as well as the time of exposure to cold and the recovery time for the correct evaluation of the symptoms. Furthermore, a comparative analysis of damage on both young and mature leaves was conducted. To validate the efficacy of the methodology, assessments were conducted on the cultivars 'Arbequina' (tolerant), 'Picual' (moderately tolerant), and 'Frantoio' (susceptible) under acclimated and non-acclimated conditions. Results and discussion: The results indicated that, when detached leaves were used for frost evaluation, a temperature of -10°C ± 1°C for 30 min and a recovery time at 26°C for 24-48 h after exposure to cold are enough to induce damages on the leaves and discriminate between cultivar susceptibility. Under these conditions, a precise assessment of symptoms can be made, facilitating the categorization of frost tolerance level in various olive cultivars. Notably, no significant differences were observed between young and mature leaves during the evaluation process. On the other hand, the critical temperature to assess damages on potted plantlets was determined to be -7°C ± 1°C. In addition, it was observed that acclimated plants exhibited fewer symptoms compared to non-acclimated ones, with 'Frantoio' being the most affected alongside 'Picual' and 'Arbequina'. Conclusion: The implemented methodology will allow the assessment of frost tolerance in several olive cultivars within a short timeframe, and it is proven to be user-friendly and reliable.
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OBJECTIVE: Readmission for COVID-19 is associated with high mortality, saturation of health services, and high costs. This study aimed to assess the incidence and risk factors of readmissions in COVID-19 patients in a regional hospital of Spain from February 2020 to March 2021. METHODS: A retrospective cohort study describing the characteristics of adult patients readmitted within thirty days of discharge after being infected with SARS-CoV-2 was carried out. Readmission associated risk factors were analysed using a binary logistic regression model. RESULTS: Of the 967 patients who survived their first COVID-19 admission, 70 (7.2%) were readmitted within thirty days. Of these, 34.3% presented pneumonia progression, 15.7% functional deterioration, and 12.9% other infections. The mortality rate during readmission was 28.6%. There were no statistically significant differences in the cumulative incidence of readmissions between the epidemic periods (p=0.241). Factors independently associated with readmission were: diabetes mellitus (aOR 1.96, 95%CI 1.07-3.57, p=0.030); acute kidney failure (aOR 2.69, 95%CI 1.43-5.07, p=0.002); not being a candidate for intensive care (aOR 7.68, 95% CI 4.28-13.80, p<0.001); and not being prescribed corticosteroids at discharge (aOR 2.15, 95% CI 1.04-4.44; p=0.039). CONCLUSIONS: A substantial proportion of patients admitted due to COVID-19 are readmitted, and they carry a high letality. Diabetes mellitus, acute kidney failure, not being a candidate for ICU admission, and not being prescribed corticosteroids on discharge are independently associated with an increased risk of readmission.
OBJECTIVE: Los reingresos por la COVID-19 se asocian a un incremento de la mortalidad, saturación de los servicios sanitarios y elevados costes. Este estudio pretendió evaluar la incidencia y los factores de riesgo de reingreso en pacientes con COVID-19 en un hospital comarcal español entre febrero de 2020 y marzo de 2021. METHODS: Se realizó un estudio sobre una cohorte que describía las características de los pacientes adultos reingresados en los treinta días siguientes al alta tras un ingreso por la COVID-19. Se analizaron los factores de riesgo asociados a reingreso mediante un modelo de regresión de logística binaria. RESULTS: De los 967 pacientes dados de alta de un primer ingreso por la COVID-19, 70 (7,2%) reingresaron en los treinta días siguientes. De ellos, el 34,3% presentó progresión de la neumonía, el 15,7% deterioro funcional y el 12,9% otras infecciones. La letalidad en el reingreso fue del 28,6%. No hubo diferencias estadísticamente significativas en la incidencia acumulada de reingreso entre los tres periodos (p=0,241). Los factores asociados de forma independiente con el reingreso fueron: diabetes mellitus (ORa: 1,96; IC 95%:1,07-3,57; p=0,030); insuficiencia renal aguda (ORa 2,69; IC del 95%: 1,43-5,07, p=0,002); no ser candidato a cuidados intensivos (ORa 7,68, IC 95% 4,28-13,80, p<0,001); y no tener prescritos corticosteroides al alta (ORa 2,15, IC 95% 1,04- 4,44; p=0,039). CONCLUSIONS: Una proporción sustancial de los pacientes ingresados por la COVID-19 reingresan, con una elevada letalidad. La diabetes mellitus, la insuficiencia renal aguda, no ser candidato a ingreso en UCI y no tener prescritos corticoides al alta se asocian con un mayor riesgo de reingreso.
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Injúria Renal Aguda , COVID-19 , Diabetes Mellitus , Adulto , Humanos , Incidência , Readmissão do Paciente , COVID-19/epidemiologia , Estudos Retrospectivos , Espanha/epidemiologia , SARS-CoV-2 , Fatores de Risco , CorticosteroidesRESUMO
A collection of 81 isolates of enteropathogenic Escherichia coli (EPEC) was obtained from samples of bulk tank sheep milk (62 isolates), ovine feces (4 isolates), sheep farm environment (water, 4 isolates; air, 1 isolate), and human stool samples (9 isolates). The strains were considered atypical EPEC organisms, carrying the eae gene without harboring the pEAF plasmid. Multilocus sequence typing (MLST) was carried out with seven housekeeping genes and 19 sequence types (ST) were detected, with none of them having been previously reported for atypical EPEC. The most frequent ST included 41 strains isolated from milk and human stool samples. Genetic typing by pulsed-field gel electrophoresis (PFGE) resulted in 57 patterns which grouped in 24 clusters. Comparison of strains isolated from the different samples showed phylogenetic relationships between milk and human isolates and also between milk and water isolates. The results obtained show a possible risk for humans due to the presence of atypical EPEC in ewes' milk and suggest a transmission route for this emerging pathogen through contaminated water.
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Eletroforese em Gel de Campo Pulsado , Escherichia coli Enteropatogênica/classificação , Escherichia coli Enteropatogênica/isolamento & purificação , Microbiologia Ambiental , Fezes/microbiologia , Leite/microbiologia , Tipagem de Sequências Multilocus , Animais , Análise por Conglomerados , Escherichia coli Enteropatogênica/genética , Genes Essenciais , Genótipo , Humanos , Filogenia , OvinosRESUMO
The design, synthesis, conformational studies and binding affinity for VEGF receptors of a collection of linear and cyclic peptide analogues of the N-terminal α-helix fragments 13-25 of VEGF and 1-13 of Vammin are described. Linear 13(14)-mer peptides were designed with the help of an AGADIR algorithm and prepared following peptide solid-phase synthetic protocols. Cyclic peptide derivatives were prepared on-resin from linear precursors with conveniently located Glu and Lys residues, by the formation of amide linkages. Conformational analysis, CD and NMR, showed that most synthesized peptides have a clear tendency to be structured as α-helices in solution. Some of the peptides were able to bind a VEGFR-1 receptor with moderate affinity. In addition to the described key residues (Phe17, Tyr21 and Tyr25), Val14 and Val20 seem to be relevant for affinity.
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Peptídeos/química , Receptores de Fatores de Crescimento do Endotélio Vascular/química , Fator A de Crescimento do Endotélio Vascular/química , Venenos de Víboras/química , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Peptídeos/síntese química , Peptídeos/metabolismo , Conformação Proteica , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismoAssuntos
Erros de Diagnóstico , Glucagonoma/complicações , Neoplasias Pancreáticas/complicações , Psoríase/diagnóstico , Dermatopatias/etiologia , Biópsia , Diagnóstico Diferencial , Glucagonoma/diagnóstico por imagem , Glucagonoma/secundário , Glucagonoma/cirurgia , Humanos , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Dermatopatias/patologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To identify the most relevant clinical characteristics of the nursing diagnosis frail elderly syndrome (FES) in hospitalized patients aged 65 or older and analyze their impact on 9-month mortality and hospital readmission. METHODS: A prospective and prognostic accuracy study was conducted in patients aged 65 or older, who were admitted to hospital more than 24 h. A consecutive convenience sampling process was used. Assessment included defining characteristics (DCs) of FES, clinical fraility scale (CFS), frail scale (FS), and 9-month mortality and hospital readmission. Statistical tests were used to verify associations between variables. Binary logistic regression analysis and area under the curve were used, to identify significant predictors for the outcomes and evaluate the prognostic accuracy of the DCs. FINDINGS: This study involved 150 patients. CFS scored 65 patients (43.3%, confidence interval 95% 35.2% a 51.6) as frail and proved a prognostic value of mortality at 9 month from pre-frail state (p = 0.020). The mean number of DCs for FES nursing diagnosis was 6.35 (SD = 3.14). Validated tools for measuring frailty were associated with all DCs, excepting nutritional imbalance: below body needs. The hospital readmission during the following 9 months was only statistically related to memory impairment (p = 0.07). CONCLUSION: Clinical frailty scale showed good results as a predictor of mortality. The study suggests exploring including it, in clinical manifestations of elderly frail syndrome. This study found that only memory impairment defining characteristic was predictive of hospital readmission. Further research should identify other relevant and prognostic clinical manifestations. IMPLICATION FOR NURSING PRACTICE: These findings highlight the importance of being vigilant on cognitive decline during hospital admissions. The most prevalent and determinant DCs identified in this study indicate that clinical should focus on preserving functional and mental abilities as well as mobility.
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AIMS: To determine adverse effects of ventrogluteal intramuscular injections versus dorsogluteal intramuscular injections. DESIGN: A systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, CINHAL, CENTRAL, LILACS(BVS), BDENF (BVS), WoS, IRCTP(WHO), ClinicalsTrials.gov and PROSPERO databases were searched with no restriction on year or language. Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: A total of 1429 participants from 17 studies were included. The meta-analysis found that ventrogluteal injection site had significant relation to lower pain in 9 studies (SMD = -0.63, 95% CI = -0.87, -0.39), bleeding in 4 studies (SMD = -3.46, 95% CI = -6.07, -0.86) and hematoma in 2 studies; after 48 h (SMD = -0.25, 95% CI = -0.39, -0.11), and after 72 h (SMD = -0.16, 95% CI = -0.26, -0.06), if it was compared with dorsogluteal site injection. No differences were found when comparing the possibility of intramuscular injections given into de subcutaneous tissue. In three studies, ventrogluteal site did not significantly reduce the risk of subcutaneous injection (OR 0,62, 95% CI = 0.16, 2.41).
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Músculo Esquelético , Gordura Subcutânea , Humanos , Injeções Intramusculares/efeitos adversos , Nádegas , Tela SubcutâneaRESUMO
Introduction: The evidence for remdesivir therapy in immunocompromised patients is scarce. To evaluate remdesivir (RDV) effectiveness and safety in COVID-19 outpatients at high risk for progression in a real-world setting, we compare the outcome in immunocompromised (IC) patients with that in non-immunocompromised patients. Methods: Two hospitals conducted a retrospective study of all adult patients with mild-to-moderate SARS-CoV-2 infection at high risk for disease progression who were treated as outpatients with a 3-day course of RDV (1st January-30th September 2022). The primary effectiveness endpoint was a composite of any cause of hospitalization or death by day 30. A multiple logistic regression model was built to explore the association between immune status and clinical outcome, estimating adjusted odds ratios [aORs (95% CI)]. Results: We have included 211 patients, of which 57% were males, with a median age of 65 years (IQR 53-77), 70.1% were vaccinated (three or four doses), and 61.1% were IC. The median duration of symptoms before RDV treatment was 3 days (IQR 2-5). During follow-up, 14 (6.6%) patients were hospitalized, of which 6 (2.8%) were hospitalized for COVID-19 progression. No patient required mechanical ventilation, and two patients died (non-COVID-19-related). After accounting for potential confounders, only anti-CD20 treatment was associated with the composed outcome [aOR 5.35 (1.02-27.5, 95% CI)], whereas the immunocompetence status was not [aOR 1.94 (0.49-7.81, 95% CI)]. Conclusion: Early COVID-19 outpatient treatment with a 3-day course of remdesivir in vaccinated patients at high risk for disease progression during the Omicron surge had a good safety profile. It was associated with a low rate of all-cause hospitalization or death, regardless of immunocompetence status.
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Objectives: To investigate the role of previous antibiotic therapy in the risk of recurrence after a Clostridioides difficile infection (CDI) treated with vancomycin. Methods: Multicentre observational study. Patients with a CDI episode achieving clinical cure with oral vancomycin and followed up 8â weeks were included. Previous antibiotic exposure up to 90â days was collected. Multivariate analysis of predictors of recurrence adjusted by the propensity score (PS) of being previously treated with each non-CDI antibiotic was performed. Results: Two hundred and forty-one patients were included; 216 (90%) had received systemic antibiotics. Fifty-three patients (22%) had a CDI recurrence. Rates of recurrence were lower in those treated with piperacillin/tazobactam in the last month when compared with those not receiving piperacillin/tazobactam [3 (7%) versus 50 (25%); Pâ=â0.01], whereas higher rates were seen in those treated with cephalosporins in the last month [26/87 (30%) versus 27/154 (17%); Pâ=â0.03]. In multivariate analysis controlled by the inverse probability of treatment weighting by PS, receiving ≥5â days of piperacillin/tazobactam in the last month as the last antibiotic regimen prior to CDI was independently associated with a lower risk of recurrence [adjusted OR (AOR) 0.13; 95% CI: 0.06-0.29; Pâ<â0.0001] whereas exposure for ≥5â days to cephalosporins (versus piperacillin/tazobactam) was associated with an increased risk (AOR 10.9; 95% CI: 4.4-27.1; Pâ<â0.0001). Conclusions: Recent use of piperacillin/tazobactam might be associated with a lower risk of CDI recurrence, while recent use of cephalosporins might promote an increased risk. These findings should be considered when treating hospitalized patients.
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INTRODUCTION: Social functioning is severely affected in psychotic disorders. Negative symptoms and social cognition seem to play an important role in social functioning, although the preponderance and relationship between these three domains is not clear. In this study, we sought to assess the interrelation between social cognition, social functioning, and the expressiveness and experiential factors of negative symptoms in first-episode psychosis (FEP). SAMPLE AND METHODS: 216 patients, participants in a multicentre study (AGES-CM), comprised our study sample. The WHO Disability Assessment Schedule (WHODAS 2.0) was used to assess functioning, whereas the Positive and Negative Schizophrenia Syndrome Scale (PANSS) was used to measure the severity of negative symptoms, and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) was applied to assess the emotional processing component of social cognition. Network analyses were conducted with the aim of analysing the patterns of relationships between social cognition, social functioning, and the expressiveness and experiential factors of negative symptoms. RESULTS: Our findings suggest that there is a direct relationship between social cognition and social functioning (weight = -.077), but also an indirect connection between them, mediated by the experiential (but not the expressiveness) factor of negative symptoms (weight = 0.300). DISCUSSION: The importance of the affectation of subdomains of social cognition, as well as the role of negative symptoms, specifically the experiential factor, in the functioning of patients with FEP seems to be relevant. The inclusion of these factors in prevention and treatment programs would thus allow us to reduce their impact on the social functioning of these patients.
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Transtornos Psicóticos , Esquizofrenia , Humanos , Transtornos Psicóticos/psicologia , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Ajustamento Social , Cognição Social , Interação SocialRESUMO
The design, synthesis, conformational studies and binding affinity for VEGFR-1 receptors of a collection of linear and cyclic peptide analogues of the ß-hairpin fragment VEGF(81-91) are described. Cyclic 11-mer peptide derivatives were prepared from linear precursors with conveniently located Cys, Asp or Dap residues, by the formation of disulfide and amide bridges, using solid-phase synthesis. Molecular modelling studies indicated a tendency to be structured around the central ß-turn of the VEGF(81-91) ß-hairpin in most synthesized cyclic compounds. This structural behavior was confirmed by NMR conformational analysis. The NHCO cyclic derivative 7 showed significant affinity for VEGFR-1, slightly higher than the native linear fragment, thus supporting the design of mimics of this fragment as a valid approach to disrupt the VEGF/VEGFR-1 interaction.
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Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Fator A de Crescimento do Endotélio Vascular/química , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Amidas/química , Sequência de Aminoácidos , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Dissulfetos/química , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Fragmentos de Peptídeos/síntese química , Peptídeos Cíclicos/síntese química , Ligação Proteica , Conformação Proteica , Técnicas de Síntese em Fase SólidaRESUMO
The design, synthesis and binding affinity for VEGFR-1 receptors of a small library of linear and cyclic analogues of the VEGF(81-91) fragment are described. Cyclic 11- and 10-mer peptide derivatives were prepared using parallel solid-phase protocols. The formation of hydrocarbon alkene-bridged cyclic peptides was achieved through optimized ring-closing metathesis reactions from linear derivatives with conveniently located allylGly residues. Alkane-bridged analogues were successfully obtained by ulterior on-resin hydrogenation. Binding assays showed that some of these compounds were able to compete with labeled VEGF for interaction with the VEGFR-1 receptor. Several peptide derivatives, 2, 7 and 8, showed modest but significant binding affinity, indicating that the designed peptide could mimic the VEGF(81-91) fragment and therefore disrupt the VEGF/VEGFR-1 interaction. This fact opens the way for using these peptides as the starting point for biological/pharmacological tools to deeply investigate this protein-protein system.