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1.
Eur J Pharm Biopharm ; : 114293, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641229

RESUMO

The characterization of the time course of ibuprofen enantiomers can be useful in the selection of the most sensitive analyte in bioequivalence studies. Physiologically based pharmacokinetic (PBPK) modelling and simulation represents the most efficient methodology to virtually assess bioequivalence outcomes. In this work, we aim to develop and verify a PBPK model for ibuprofen enantiomers administered as a racemic mixture with different immediate release dosage forms to anticipate bioequivalence outcomes based on different particle size distributions. A PBPK model incorporating stereoselectivity and non-linearity in plasma protein binding and metabolism as well as R-to-S unidirectional inversion has been developed in Simcyp®. A dataset composed of 11 Phase I clinical trials with 54 scenarios (27 per enantiomer) and 14,452 observations (7129 for R-ibuprofen and 7323 for S-ibuprofen) was used. Prediction errors for AUC0-t and Cmax for both enantiomers fell within the 0.8-1.25 range in 50/54 (93 %) and 42/54 (78 %) of scenarios, respectively. Outstanding model performance, with 10/10 (100 %) of Cmax and 9/10 (90 %) of AUC0-t within the 0.9-1.1 range, was demonstrated for oral suspensions, which strongly supported its use for bioequivalence risk assessment. The deterministic bioequivalence risk assessment has revealed R-ibuprofen as the most sensitive analyte to detect differences in particle size distribution for oral suspensions containing 400 mg of racemic ibuprofen, suggesting that achiral bioanalytical methods would increase type II error and declare non-bioequivalence for formulations that are bioequivalent for the eutomer.

2.
Arch Bronconeumol ; 2024 Apr 06.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38644153

RESUMO

INTRODUCTION: Cold static donor lung preservation at 10°C appears to be a promising method to safely extend the cold ischemic time (CIT) and improve lung transplant (LTx) logistics. METHODS: LTx from November 2021 to February 2023 were included in this single institution, prospective, non-randomized study comparing prolonged preservation at 10°C versus standard preservation on ice. The inclusion criteria for 10°C preservation were suitable grafts for LTx without any donor retrieval concerns. PRIMARY ENDPOINT: primary graft dysfunction (PGD) grade-3 at 72-h. Secondary endpoints: clinical outcomes, cytokine profile and logistical impact. RESULTS: Thirty-three out of fifty-seven cases were preserved at 10°C. Donor and recipient characteristics were similar across the groups. Total preservation times (h:min) were longer (p<0.001) in the 10°C group [1st lung: median 12:09 (IQR 9:23-13:29); 2nd: 14:24 (12:00-16:20)] vs. standard group [1st lung: median 5:47 (IQR 5:18-6:40); 2nd: 7:15 (6:33-7:40)]. PGD grade-3 at 72-h was 9.4% in 10°C group vs. 12.5% in standard group (p=0.440). Length of mechanical ventilation (MV), ICU and hospital stays were similar in both groups. Thirty and ninety-day mortality rates were 0% in 10°C group (vs. 4.2% in standard group). IL-8 concentration was significantly higher 6-h post-LTx in the standard group (p=0.025) and IL-10 concentration was increased 72-h post-LTx in the 10°C group (p=0.045). CONCLUSIONS: Preservation at 10°C may represent a safe and feasible strategy to intentionally prolong the CIT. In our center, extending the CIT at 10°C may allow for semi-elective LTx and improve logistics with similar outcomes compared to the current standard preservation on ice.

4.
J Am Coll Cardiol ; 83(17): 1640-1651, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38658103

RESUMO

BACKGROUND: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. RESULTS: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.


Assuntos
Cardiomiopatia Dilatada , Genótipo , Penetrância , Humanos , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Seguimentos , Espanha/epidemiologia , Eletrocardiografia , Conectina/genética
5.
Cancers (Basel) ; 16(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38610963

RESUMO

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

6.
J Thromb Thrombolysis ; 57(4): 650-657, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38491266

RESUMO

BACKGROUND: The interrelation of cancer with venous thromboembolism is established, yet the specific impact on the incidence and progression of superficial vein thrombosis (SVT) remains unclear. OBJECTIVES: To investigate the association between SVT and malignancies, focusing on risk factors, presentation, course and complications. METHODS: A single-center prospective observational study of patients diagnosed with DVT or SVT referred to a venous thromboembolism clinic between January 2013 and April 2018. RESULTS: Of the 632 patients, 205 presented with SVT at referral, 16.6% having active cancer. Significant associations were found between active cancer and the risk of developing proximal SVT (RR 1.54 [1.18-2.03] p < 0.01), SVT within 3 cm from junction (RR 2.01 [1.13-3.72] p = 0.019), bilateral SVT (RR 8.38 [2.10-33.43] p < 0.01) and SVT affecting multiple veins (RR 2.42 [1.40-4.20] p < 0.01), with a higher risk of persistence (RR 1.51 [1.18-1.95] p < 0.01) and progression (RR 5.75 [2.23-14.79] p < 0.01) at initial assessment. Patients with SVT and no malignancy history demonstrated an elevated risk for new-onset cancer during follow-up (RR 1.43 [1.13-1.18] p = 0.022), especially in cases of proximal or bilateral SVT, initial progression or subsequent DVT or PE. No significant differences were observed in persistence, recurrence or complications during initial evaluation or follow-up across different pharmacological treatments. CONCLUSIONS: Research suggests a probable link between cancer history and the development of SVT. SVT presented more severely in cancer patients. SVT, especially in its more complex forms, could serve as a predictive marker for the future development of cancer. Treatment approaches varied, no significant differences in outcomes were noted.


Assuntos
Neoplasias , Tromboembolia Venosa , Trombose Venosa , Humanos , Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/uso terapêutico , Trombose Venosa/diagnóstico , Fatores de Risco , Neoplasias/complicações
7.
Microorganisms ; 12(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38543658

RESUMO

Approximately a quarter of patients with infective endocarditis (IE) who have surgical indication only receive antibiotic treatment. Their short-term prognosis is dismal. We aimed to describe the characteristics of this group of patients to evaluate the mortality according to the cause of rejection and type of surgical indication and to analyze their prognostic factors of mortality. From 2005 to 2022, 1105 patients with definite left-sided IE were consecutively attended in three tertiary hospitals. Of them, 912 (82.5%) had formal surgical indication according to the most recent European Guidelines available in each period of the study and 303 (33%) only received medical treatment. These were older, had more comorbidities and higher in-hospital (46% vs. 24%; p < 0.001) and one year mortality (57.1% vs. 27.6%; p < 0.001) than operated patients. The main reason for surgical rejection was high surgical risk (57.1%) and the highest mortality when the cause were severe neurological conditions (76%). When the endocarditis team took the decision not to operate (25.5% of the patients), in-hospital (7%) and one-year mortality (17%) were low. In-hospital mortality associated with each surgical indication was 67% in heart failure, 53% in uncontrolled infection and 45% in prevention of embolisms (p < 0.001). Heart failure (OR: 2.26 CI95%: 1.29-3.96; p = 0.005), Staphylococcus aureus (OR: 3.17; CI95%: 1.72-5.86; p < 0.001) and persistent infection (OR: 5.07 CI95%: 2.85-9.03) are the independent risk factors of in-hospital mortality. One third of the patients with left-sided IE and formal surgical indication are rejected for surgery. In-hospital mortality is very high, especially when heart failure is the indication for surgery and when severe neurological conditions the reason for rejection. Short term prognosis of patients rejected by a specialized endocarditis team is favorable.

8.
Endocrinol Diabetes Nutr (Engl Ed) ; 71(2): 53-60, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38493008

RESUMO

SUBJECT-MATTER: To assess the effect of the 2019 coronavirus (COVID-19) pandemic on gestational diabetes (GDM). MATERIAL AND METHODS: In this retrospective, multicentre, non-interventional study carried out in Castilla-La Mancha, Spain, we compared 663 women with GDM exposed to the pandemic (pandemic group), with 622 women with GDM seen one year earlier (pre-pandemic group). The primary endpoint was a Large for Gestational Age (LGA) newborn as an indicator of poor GDM control. Secondary endpoints included obstetric and neonatal complications. RESULTS: During the pandemic, the gestational week at diagnosis (24.2 ±â€¯7.4 vs 22.9 ±â€¯7.7, p = 0.0016) and first visit to Endocrinology (26.6 ±â€¯7.2 vs 25.3 ±â€¯7.6, p = 0.0014) were earlier. Face-to-face consultations were maintained in most cases (80.3%). The new diagnostic criteria for GDM were used in only 3% of cases. However, in the pandemic group, the final HbA1c was higher (5.2 ±â€¯0.48 vs 5.29 ±â€¯0.44%, p = 0.047) and there were more LGA newborns (8.5% vs 12.8%, p = 0.015). There were no differences in perinatal complications. CONCLUSIONS: Care for GDM in our Public Health System did not significantly deteriorate during the COVID-19 pandemic. However, this did not prevent a higher number of LGA newborns.


Assuntos
COVID-19 , Diabetes Gestacional , Gravidez , Recém-Nascido , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/diagnóstico , Pandemias , Resultado da Gravidez , Estudos Retrospectivos , Espanha/epidemiologia
9.
Front Hum Neurosci ; 18: 1362742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516308

RESUMO

Introduction: Low frequency (1 Hz) repetitive transcranial stimulation (rTMS) applied over right posterior parietal cortex (rPPC) has been shown to reduce cortical excitability both of the stimulated area and of the interconnected contralateral homologous areas. In the present study, we investigated the whole pattern of intra- and inter-hemispheric cortico-cortical connectivity changes induced by rTMS over rPPC. Methods: To do so, 14 healthy participants underwent resting state EEG recording before and after 30 min of rTMS at 1 Hz or sham stimulation over the rPPC (electrode position P6). Real stimulation was applied at 90% of motor threshold. Coherence values were computed on the electrodes nearby the stimulated site (i.e., P4, P8, and CP6) considering all possible inter- and intra-hemispheric combinations for the following frequency bands: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12Hz), low beta (12-20 Hz), high beta (20-30 Hz), and gamma (30-50 Hz). Results and discussion: Results revealed a significant increase in coherence in delta, theta, alpha and beta frequency bands between rPPC and the contralateral homologous sites. Moreover, an increase in coherence in theta, alpha, beta and gamma frequency bands was found between rPPC and right frontal sites, reflecting the activation of the fronto-parietal network within the right hemisphere. Summarizing, subthreshold rTMS over rPPC revealed cortico-cortical inter- and intra-hemispheric connectivity as measured by the increase in coherence among these areas. Moreover, the present results further confirm previous evidence indicating that the increase of coherence values is related to intra- and inter-hemispheric inhibitory effects of rTMS. These results can have implications for devising evidence-based rehabilitation protocols after stroke.

10.
Womens Health (Lond) ; 20: 17455057241231477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523351

RESUMO

BACKGROUND: Scarce evidence exists on barriers to physical activity in Mexican women. Despite evidence from other countries, no research has investigated the influence of the breast on PA in this population. OBJECTIVE: To determine the association between the breast and physical activity in Mexican women. DESIGN: Cross-sectional observational study. METHODS: Volunteers were 279 Mexican women from Veracruz, Durango, and Baja California states, who completed a paper survey of their demographics, brassiere characteristics, breast pain, and frequency and amounts of weekly physical activity. RESULTS: The first barrier to physical activity was time constraints, followed by breast-related issues. Breast pain was reported by 47.1% of women, and the breast as a barrier to physical activity participation was reported by 30.6%. Responses, such as "I am embarrassed by excessive breast movement" and "My breasts are too big" were the most frequently reported breast-related barriers to physical activity. Breast pain was associated with the menstrual cycle and exercise. Breast health knowledge and pain intensity were unrelated to moderate- and vigorous-intensity physical activity. The 36.4% and 6.7% of women did not meet weekly moderate- and vigorous-intensity physical activity guidelines, respectively. Weekly moderate- and vigorous-intensity physical activity was similar between women reporting breast pain and those who did not. CONCLUSIONS: Because the breast was the second most significant barrier to physical activity, it is imperative to increase breast health knowledge in Mexican women to reduce impediments to physical activity.


Perception of Mexican women regarding their breasts as a barrier to physical activityPhysical activity provides numerous health benefits, sometimes associated with reversing or delaying several diseases. However, barriers to increasing physical activity in women remain, as the breast is an anatomical aspect that is unique to women. Breast pain has been reported in more than 50% of women who perform physical exercise. Therefore, the study aimed to determine the associations between breast characteristics and barriers to physical activity in Mexican women. Two hundred and seventy-nine women from three Mexican states voluntarily participated in the study. They answered survey questions on the history of bra use, barriers to physical activity, and essential demographic characteristics. The main findings of this study were that issues related to the breasts were reported as the second barrier to physical activity participation. In addition, time constraints were reported as the main reason impeding physical activity participation. Public health initiatives should support attempts to increase breast satisfaction among women of all breast sizes to stimulate engagement in physical activity throughout their lives.


Assuntos
Mastodinia , Feminino , Humanos , Estudos Transversais , México , Mama , Exercício Físico
12.
Biofilm ; 7: 100178, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38317668

RESUMO

Biofilm formation by the pathobiont Haemophilus influenzae is associated with human nasopharynx colonization, otitis media in children, and chronic respiratory infections in adults suffering from chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). ß-lactam and quinolone antibiotics are commonly used to treat these infections. However, considering the resistance of biofilm-resident bacteria to antibiotic-mediated killing, the use of antibiotics may be insufficient and require being replaced or complemented with novel strategies. Moreover, unlike the standard minimal inhibitory concentration assay used to assess antibacterial activity against planktonic cells, standardization of methods to evaluate anti-biofilm drug activity is limited. In this work, we detail a panel of protocols for systematic analysis of drug antimicrobial effect on bacterial biofilms, customized to evaluate drug effects against H. influenzae biofilms. Testing of two cinnamaldehyde analogs, (E)-trans-2-nonenal and (E)-3-decen-2-one, demonstrated their effectiveness in both H. influenzae inhibition of biofilm formation and eradication or preformed biofilms. Assay complementarity allowed quantifying the dynamics and extent of the inhibitory effects, also observed for ampicillin resistant clinical strains forming biofilms refractory to this antibiotic. Moreover, cinnamaldehyde analog encapsulation into poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles allowed drug vehiculization while maintaining efficacy. Overall, we demonstrate the usefulness of cinnamaldehyde analogs against H. influenzae biofilms, present a test panel that can be easily adapted to a wide range of pathogens and drugs, and highlight the benefits of drug nanoencapsulation towards safe controlled release.

13.
Parasit Vectors ; 17(1): 61, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342888

RESUMO

BACKGROUND: Usutu virus (USUV), which is closely related to West Nile virus (WNV), sharing a similar ecology and transmission cycle, was first reported in the UK in the southeast of England in 2020. Both USUV and WNV are emerging zoonotic viruses hosted by wild birds. The 2020 finding of USUV in England raised awareness of this virus and highlighted the importance of understanding the seasonality of Culex pipiens sensu lato (Cx. pipiens s.l.), the main enzootic vector of these viruses. Zoos are prime locations for trapping mosquitoes because of their infrastructure, security, and range of vertebrate hosts and aquatic habitats. METHODS: Three independent zoo-based case studies at four locations that cover the seasonality of Cx. pipiens s.l. in England were undertaken: (i) London Zoo (Zoological Society London [ZSL]) and surrounding areas, London; (ii) Chester Zoo (Cheshire); (ii) Twycross Zoo (Leicestershire); and (iv) Flamingo Land (zoo; North Yorkshire). Various adult mosquito traps were used to catch adult Cx. pipiens s.l. across seasons. RESULTS: High yields of Cx. pipiens s.l./Culex torrentium were observed in Biogents-Mosquitaire and Center for Disease Control and Prevention Gravid traps in all studies where these traps were used. Mosquito counts varied between sites and between years. Observations of adult Cx. pipiens s.l./Cx. torrentium abundance and modelling studies demonstrated peak adult abundance between late July and early August, with active adult female Cx. pipiens s.l./Cx. torrentium populations between May and September. CONCLUSIONS: The information collated in this study illustrates the value of multiple mosquito monitoring approaches in zoos to describe the seasonality of this UK vector across multiple sites in England and provides a framework that can be used for ongoing and future surveillance programmes and disease risk management strategies.


Assuntos
Culex , Culicidae , Flavivirus , Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Feminino , Animais , Mosquitos Vetores , Inglaterra
14.
Neuropsychologia ; 196: 108839, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38401630

RESUMO

The existence of unconscious visually triggered behavior in patients with cortical blindness (e.g., homonymous hemianopia) has been amply demonstrated and the neural bases of this phenomenon have been thoroughly studied. However, a crosstalk between the two hemispheres as a possible mechanism of unconscious or partially conscious vision has not been so far considered. Thus, the aim of this study was to assess the relationship between structural and functional properties of the corpus callosum (CC), as shown by probabilistic tractography (PT), behavioral detection/discrimination performance and level of perceptual awareness in the blind field of patients with hemianopia. Twelve patients were tested in two tasks with black-and-white visual square-wave gratings, one task of movement and the other of orientation. The stimuli were lateralized to one hemifield either intact or blind. A PT analysis was carried out on MRI data to extract fiber properties along the CC (genu, body, and splenium). Compared with a control group of participants without brain damage, patients showed lower FA values in all three CC sections studied. For the intact hemifield we found a significant correlation between PT values and visual detection/discrimination accuracy. For the blind hemifield the level of perceptual awareness correlated with PT values for all three CC sections in the movement task. Importantly, significant differences in all three CC sections were found also between patients with above-vs. chance detection/discrimination performance while differences in the genu were found between patients with and without perceptual awareness. Overall, our study provides evidence that the properties of CC fibers are related to the presence of unconscious stimulus detection/discrimination and to hints of perceptual awareness for stimulus presentation to the blind hemifield. These results underline the importance of information exchange between the damaged and the healthy hemisphere for possible partial or full recovery from hemianopia.


Assuntos
Cegueira Cortical , Hemianopsia , Humanos , Hemianopsia/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Percepção Visual , Inconsciência , Estimulação Luminosa
15.
Heliyon ; 10(4): e26477, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404807

RESUMO

The emergence of several zoonotic mosquito-borne pathogens in Europe, including West Nile virus, Sindbis virus and Usutu virus, has emphasised the importance of consistent surveillance. Considerable fieldwork effort is usually needed to detect low-prevalence pathogens in mosquitoes and screening vertebrate hosts and reservoirs is rarely done simultaneously with mosquito sampling. Zoological gardens offer an opportunity for the surveillance of pathogens, mosquitoes, hosts, and reservoirs concurrently; thus, the aim of this study was undertaking integrated surveillance for mosquito-borne pathogens of wild birds and mosquitoes in Chester Zoo (Cheshire) in the United Kingdom. Mosquitoes were collected in September 2020 and tested for zoonotic bird-hosted arboviruses (i.e., West Nile virus, Usutu virus and Sindbis virus) using RT-qPCRs. Of the 3316 mosquitoes trapped, 98% were identified as Culex spp. The average minimum prevalence of the viruses found in the literature was used to calculate the sample size needed for detecting these viruses with 99% confidence. The testing of 2878 Culex females found no evidence of presence of the three viruses. Significant differences were found in mosquito abundance per sampling site and collection date; furthermore, important sources of immature and resting mosquitoes were found near aviaries. Eighteen wild birds belonging to 11 species were found dead in the zoo from May to December 2020 and were RT-qPCR tested for West Nile virus and Usutu virus; all samples resulted negative for viral infection. It is unlikely that these viruses were present in the zoo during the sampling period; however, since they circulate in Europe and Usutu virus has been isolated in the United Kingdom and may overwinter here, continued monitoring of mosquitoes and wild birds is recommended as virus introduction and dissemination are possible. This study highlights the importance of regular and integrated arboviral surveillance of zoonotic pathogens in zoos providing baseline information to that end.

16.
Nat Med ; 30(1): 279-289, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38200255

RESUMO

The Cancer Programme of the 100,000 Genomes Project was an initiative to provide whole-genome sequencing (WGS) for patients with cancer, evaluating opportunities for precision cancer care within the UK National Healthcare System (NHS). Genomics England, alongside NHS England, analyzed WGS data from 13,880 solid tumors spanning 33 cancer types, integrating genomic data with real-world treatment and outcome data, within a secure Research Environment. Incidence of somatic mutations in genes recommended for standard-of-care testing varied across cancer types. For instance, in glioblastoma multiforme, small variants were present in 94% of cases and copy number aberrations in at least one gene in 58% of cases, while sarcoma demonstrated the highest occurrence of actionable structural variants (13%). Homologous recombination deficiency was identified in 40% of high-grade serous ovarian cancer cases with 30% linked to pathogenic germline variants, highlighting the value of combined somatic and germline analysis. The linkage of WGS and longitudinal life course clinical data allowed the assessment of treatment outcomes for patients stratified according to pangenomic markers. Our findings demonstrate the utility of linking genomic and real-world clinical data to enable survival analysis to identify cancer genes that affect prognosis and advance our understanding of how cancer genomics impacts patient outcomes.


Assuntos
Glioblastoma , Medicina de Precisão , Humanos , Genômica , Oncogenes , Mutação em Linhagem Germinativa/genética
17.
Sci Rep ; 14(1): 1226, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216624

RESUMO

Although the ecological network approach has substantially contributed to the study of plant-pollinator interactions, current understanding of their functional structure is biased towards diurnal pollinators. Nocturnal pollinators have been systematically ignored despite the publication of several studies that have tried to alleviate this diurnal bias. Here, we explored whether adding this neglected group of pollinators had a relevant effect on the overall architecture of three high mountain plant-pollinator networks. Including nocturnal moth pollinators modified network properties by decreasing total connectivity, connectance, nestedness and robustness to plant extinction; and increasing web asymmetry and modularity. Nocturnal moths were not preferentially connected to the most linked plants of the networks, and they were grouped into a specific "night" module in only one of the three networks. Our results indicate that ignoring the nocturnal component of plant-pollinator networks may cause changes in network properties different from those expected from random undersampling of diurnal pollinators. Consequently, the neglect of nocturnal interactions may provide a distorted view of the structure of plant-pollinator networks with relevant implications for conservation assessments.


Assuntos
Mariposas , Polinização , Animais , Plantas , Insetos
18.
Biomimetics (Basel) ; 9(1)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38275459

RESUMO

(1) Background: The aim was to perform a literature review on customized subperiosteal implants (CSIs) and provide clinical guidelines based on the results of an expert consensus meeting held in 2023. (2) Methods: A literature search was performed in Pubmed (MEDLINE) in July 2023, including case series and cohort studies with a minimum follow-up of 6 months that analyzed totally or partially edentulous patients treated with CSIs. Previously, an expert consensus meeting had been held in May 2023 to establish the most relevant clinical guidelines. (3) Results: Six papers (four case series and two retrospective cohort studies) were finally included in the review. Biological and mechanical complication rates ranged from 5.7% to 43.8% and from 6.3% to 20%, respectively. Thorough digital planning to ensure the passive fit of the CSI is mandatory to avoid implant failure. (4) Conclusions: CSIs are a promising treatment option for rehabilitating edentulous patients with atrophic jaws; they seem to have an excellent short-term survival rate, a low incidence of major complications, and less morbidity in comparison with complex bone grafting procedures. As the available data on the use of CSIs are very scarce, it is not possible to establish clinical recommendations based on scientific evidence.

19.
Int J Sports Physiol Perform ; 19(3): 271-279, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38167650

RESUMO

PURPOSE: To examine the effects of 4 programming models (linear [LP], undulating [UP], reverse [RP], and constant [CP]) on physical performance. METHODS: Forty-eight moderately strength-trained men were randomly assigned to LP, UP, RP, and CP groups according to their 1-repetition maximum (1RM) in the full-squat exercise (SQ) and followed an 8-week training intervention using the SQ and monitoring movement velocity for every repetition. All groups trained with similar mean relative intensity (65% 1RM), number of repetitions (240), sets (3), and interset recovery (4 min) throughout the training program. Pretraining and posttraining measurements included, in the SQ, 1RM load, the average velocity attained for all absolute loads common to pretests and posttests (AV), and the average velocity for loads that were moved faster (AV > 1) and slower (AV < 1) than 1 m·s-1 at pretraining tests. Moreover, countermovement jump height and 20-m running sprint time were measured. RESULTS: A significant time effect was found for all variables analyzed (P < .05), except for 20-m running sprint time. Significant group × time interactions were observed for 1RM, AV > 1, and AV (P < .05). After training, all groups attained significant strength gains on 1RM, AV, AV > 1, and AV < 1 (P < .001-.01). LP and RP groups improved their countermovement jump height (P < .01), but no significant changes were observed for UP and CP. No significant improvements were achieved in 20-m running sprint time for any groups. CONCLUSIONS: These different programming models are all suitable for improving physical performance. LP and RP induce similar or greater gains in physical performance than UP and CP.


Assuntos
Desempenho Atlético , Treinamento de Força , Corrida , Masculino , Humanos , Força Muscular , Postura
20.
J Esthet Restor Dent ; 36(3): 511-519, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38059691

RESUMO

OBJECTIVE: To evaluate the optical properties and the relative translucency parameter of Ceramill ZI White (3Y-TZP) and Ceramill Zolid FX White (5Y-PSZ) zirconia ceramic systems and compare them with those of the bovine dentin and enamel/dentin structures. MATERIALS AND METHODS: 3Y-TZP and 5Y-PSZ zirconia ceramic systems were evaluated. A 0.5-mm-thick 3Y-TZP (3Y-NC.5), 0.5-mm-thick (5Y-NC.5), and 1.4-mm-thick (5Y-C.14) were used. A 0.5-mm-thick dentin specimens and 1.4-mm-thick enamel/dentin specimens (n = 5) were obtained from anterior bovine maxillary teeth. Scattering, absorption, transmittance, and albedo coefficient were calculated using Kubelka-Munk's model. Data were statistically analyzed using Kruskal-Wallis and Mann-Whitney tests (p < 0.001), and goodness-of-fit coefficient (GFC). Relative translucency parameter differences were evaluated using translucency thresholds. RESULTS: Reflectance, scattering, absorption, and transmittance properties were wavelength dependent. Good matches (GFC ≥ 0.999) in spectral reflectance were observed between 0.5-mm-thick dentin and 1.4-mm-thick enamel/dentin, and 3Y-NC.5 and 5Y-NC.5. Scattering was the main optical extinction process during light interaction with zirconia and dental structures, as indicated by albedo coefficient. Translucency differences were acceptable only for 3Y-NC.5 and the dentin structure, and 5Y-C.14 and the enamel/dentin structure. CONCLUSIONS: Optical properties of 3Y-TZP and 5Y-PSZ dental zirconia differed from each other and from bovine dental structures. Nevertheless, 3Y-TZP showed similar relative translucency parameter to bovine dentin. CLINICAL SIGNIFICANCE: To achieve the best esthetic results in restorative dentistry, it is crucial for clinicians to know about the optical properties of 3Y-TZP and 5Y-PSZ and to be able to compare these properties with those of dental structures.


Assuntos
Cerâmica , Zircônio , Bovinos , Animais , Teste de Materiais , Zircônio/química , Dentina/química , Propriedades de Superfície , Materiais Dentários
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