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1.
Open Forum Infect Dis ; 11(3): ofae062, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38524221

RESUMO

Background: Despite its global significance, challenges associated with understanding the epidemiology and accurately detecting, measuring, and characterizing the true burden of seasonal influenza remain in many resource-poor settings. Methods: A prospective observational study was conducted in Cambodia at 28 health facilities between 2007 and 2020 utilizing passive surveillance data of patients presenting with acute undifferentiated febrile illness (AUFI) to describe the prevalence of influenza A and B and characterize associated risk factors and symptoms using a questionnaire. A comparison of rapid influenza diagnostic tests (RIDTs) and real-time reverse transcription polymerase chain reaction (rRT-PCR) results was also conducted. Results: Of 30 586 total participants, 5634 (18.4%) tested positive for either influenza A or B, with 3557 (11.6%) positive for influenza A and 2288 (7.5%) positive for influenza B during the study. Influenza A and B were strongly associated with the rainy season (odds ratio [OR], 2.30; P < .001) and being from an urban area (OR, 1.45; P < .001). Analysis of individual symptoms identified cough (OR, 2.8; P < .001), chills (OR, 1.4; P < .001), and sore throat (OR, 1.4; P < .001) as having the strongest positive associations with influenza among patients with AUFI. Analysis comparing RIDTs and rRT-PCR calculated the overall sensitivity of rapid tests to be 0.492 (95% CI, 0.479-0.505) and specificity to be 0.993 (95% CI, 0.992-0.994) for both influenza type A and B. Conclusions: Findings from this 14-year study include describing the epidemiology of seasonal influenza over a prolonged time period and identifying key risk factors and clinical symptoms associated with infection; we also demonstrate the poor sensitivity of RIDTs in Cambodia.

2.
Diabetes ; 73(3): 374-384, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37870907

RESUMO

Excess body fat is a risk factor for metabolic diseases and is a leading preventable cause of morbidity and mortality worldwide. There is a strong need to find new treatments that decrease the burden of obesity and lower the risk of obesity-related comorbidities, including cardiovascular disease and type 2 diabetes. Pharmacologic mitochondrial uncouplers represent a potential treatment for obesity through their ability to increase nutrient oxidation. Herein, we report the in vitro and in vivo characterization of compound SHD865, the first compound to be studied in vivo in a newly discovered class of imidazolopyrazine mitochondrial uncouplers. SHD865 is a derivative of the furazanopyrazine uncoupler BAM15. SHD865 is a milder mitochondrial uncoupler than BAM15 that results in a lower maximal respiration rate. In a mouse model of diet-induced adiposity, 6-week treatment with SHD865 completely restored normal body composition and glucose tolerance to levels like those of chow-fed controls, without altering food intake. SHD865 treatment also corrected liver steatosis and plasma hyperlipidemia to normal levels comparable with chow-fed controls. SHD865 has maximal oral bioavailability in rats and slow clearance in human microsomes and hepatocytes. Collectively, these data identify the potential of imidazolopyrazine mitochondrial uncouplers as drug candidates for the treatment of obesity-related disorders.


Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Camundongos , Ratos , Humanos , Animais , Adiposidade , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/etiologia , Fígado/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL
3.
Curr Zool ; 69(5): 514-526, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37637311

RESUMO

Dietary studies are essential to unravel the functioning of ecosystems and ultimately to understand biodiversity. This task, which at first may seem simple, becomes especially complex in those cases of omnivorous species with highly variable diets. In this regard, the emergence of next-generation DNA sequencing methodologies represents a powerful tool to address the problem. Here we implement a high-throughput metabarcoding strategy based on the analysis of four molecular markers aimed at sequencing both mitochondrial (animal prey) and chloroplast (diet plants) genome fragments from fecal samples of two lizard species endemic to the Balearic Archipelago (Podarcis lilfordi and P. pityusensis) obtained through non-invasive methods. The results allowed for the characterization of their diets with a high degree of taxonomic detail and have contributed a large number of new trophic records. The reported diets are based mainly on the consumption of arthropods, mollusks and plants from a diversity of taxonomic orders, as well as carrion and marine subsidies. Our analyses also reveal inter- and intra-specific differences both in terms of seasonality and geographical distribution of the sampled lizard populations. These molecular findings provide new insights into the trophic interactions of these threatened endemic lizards in their unique and isolated ecosystems.

4.
Front Endocrinol (Lausanne) ; 14: 1104441, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37223011

RESUMO

Cardiac adipose tissue (CAT) has become an important target for the reduction of disease risk. Supervised exercise programs have shown potential to "significantly" reduce CAT; however, the impact of different exercise modalities is not clear, and the relationships between CAT, physical activity (PA) levels and fitness (PFit) remain unknown. Therefore, the purpose of this study was to analyze the relationships between CAT, PA and PFit, and to explore the effects of different exercise modalities in a group of women with obesity. A total of 26 women (age: 23.41 ± 5.78 years-old) were enrolled in the cross-sectional study. PA, cardiorespiratory fitness, muscular strength, body composition and CAT were evaluated. The pilot intervention included 16 women randomized to a control (CON, n=5), high intensity interval training (HIIT, n = 5) and high-intensity circuit training (HICT, n=6) groups. Statistical analysis showed negative correlations between CAT and vigorous PA (VPA) (r s=-0.41, p=0.037); and between percent body fat (%BF), fat mass (FM), and all PA levels (r s=-0.41- -0.68, p<0.05); while muscle mass was positively associated with moderate-to-vigorous PA, and upper-body lean mass with all PA levels (r s =0.40-0.53, p<0.05). The HICT intervention showed significant improvements (p<0.05) in %BF, FM, fat free mass, and whole-body and lower extremities lean mass and strength after three weeks; however, only leg strength and upper extremities' FM improved significantly compared to CON and HICT. In conclusion, although all types of PA showed a positive influence on body fat content, only VPA significantly impacted on CAT volume. Moreover, three weeks of HICT induced positive changes in PFit in women with obesity. Further research is needed to explore VPA levels and high-intensity exercise interventions for short- and long-term CAT management.


Assuntos
Tecido Adiposo , Obesidade , Feminino , Humanos , Estudos Transversais , Projetos Piloto , Obesidade/terapia , Exercício Físico
5.
Emerg Microbes Infect ; 12(1): 2208678, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37101375

RESUMO

Prospective cohort study to investigate the potential exposure to the Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) following Hajj pilgrims is still very limited. Here, we report the antibody seroconversion study results obtained from successive three years cohort studies (2016-2018) involving the Malaysian Hajj pilgrims returning from the Middle East. A cohort study of Hajj pilgrims from Malaysia enrolled 2,863 participants from 2016-2018, all of whom consented to provide paired blood samples for both pre- and post-Hajj travel to the Middle East. ELISAs and micro-neutralization assays were performed to detect the presence of MERS-CoV IgG antibodies. Sociodemographic data, symptoms experienced during Hajj, and history of exposure to camels or camel products were recorded using structured pre- and post-Hajj questionnaires. A 4-fold increase in anti-MERS-CoV IgG between paired pre-Hajj and post-Hajj serum samples in twelve participants was observed. None of the twelve ELISA-positive sera had detectable levels of virus-neutralizing antibodies. All reportedly had mild symptoms of respiratory symptoms at a certain point during the pilgrimage, implying mild or asymptomatic infections. No association between post-Hajj serum positivity and a history of exposure to camels or camel products was obtained. Findings from the study suggest that serologic conversion to MERS-CoV occurred in at least 0.6% of the Hajj pilgrims returning from the Middle East. Since all the seroconvertants had mild to no symptoms during the sampling period, it highlights the likelihood of occurrence of only low infectivity spillover infections among the Hajj pilgrims.


Assuntos
Infecções por Coronavirus , Coronavírus da Síndrome Respiratória do Oriente Médio , Animais , Camelus , Estudos Prospectivos , Estudos de Coortes , Soroconversão , Oriente Médio/epidemiologia , Viagem , Arábia Saudita/epidemiologia
6.
Virus Evol ; 9(1): veac121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36654682

RESUMO

The first case of coronavirus disease 2019 (COVID-19) in Cambodia was confirmed on 27 January 2020 in a traveller from Wuhan. Cambodia subsequently implemented strict travel restrictions, and although intermittent cases were reported during the first year of the COVID-19 pandemic, no apparent widespread community transmission was detected. Investigating the routes of severe acute respiratory coronavirus 2 (SARS-CoV-2) introduction into the country was critical for evaluating the implementation of public health interventions and assessing the effectiveness of social control measures. Genomic sequencing technologies have enabled rapid detection and monitoring of emerging variants of SARS-CoV-2. Here, we detected 478 confirmed COVID-19 cases in Cambodia between 27 January 2020 and 14 February 2021, 81.3 per cent in imported cases. Among them, fifty-four SARS-CoV-2 genomes were sequenced and analysed along with representative global lineages. Despite the low number of confirmed cases, we found a high diversity of Cambodian viruses that belonged to at least seventeen distinct PANGO lineages. Phylogenetic inference of SARS-CoV-2 revealed that the genetic diversity of Cambodian viruses resulted from multiple independent introductions from diverse regions, predominantly, Eastern Asia, Europe, and Southeast Asia. Most cases were quickly isolated, limiting community spread, although there was an A.23.1 variant cluster in Phnom Penh in November 2020 that resulted in a small-scale local transmission. The overall low incidence of COVID-19 infections suggests that Cambodia's early containment strategies, including travel restrictions, aggressive testing and strict quarantine measures, were effective in preventing large community outbreaks of COVID-19.

7.
Microb Ecol ; 85(4): 1564-1577, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35482107

RESUMO

Gut microbial communities provide essential functions to their hosts and are known to influence both their ecology and evolution. However, our knowledge of these complex associations is still very limited in reptiles. Here we report the 16S rRNA gene faecal microbiota profiles of two lizard species endemic to the Balearic archipelago (Podarcis lilfordi and P. pityusensis), encompassing their allopatric range of distribution through a noninvasive sampling, as an alternative to previous studies that implied killing specimens of these IUCN endangered and near-threatened species, respectively. Both lizard species showed a faecal microbiome composition consistent with their omnivorous trophic ecology, with a high representation of cellulolytic bacteria taxa. We also identified species-specific core microbiota signatures and retrieved lizard species, islet ascription, and seasonality as the main factors in explaining bacterial community composition. The different Balearic Podarcis populations are characterised by harbouring a high proportion of unique bacterial taxa, thus reinforcing their view as unique and divergent evolutionary entities.


Assuntos
Lagartos , Microbiota , Animais , Lagartos/microbiologia , Espanha , RNA Ribossômico 16S/genética , Fezes
8.
BMC Infect Dis ; 22(1): 949, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36526991

RESUMO

BACKGROUND: In 2020, the Kingdom of Cambodia experienced a nationwide outbreak of chikungunya virus (CHIKV). Despite an increase in the frequency of outbreaks and expanding geographic range of CHIKV, diagnostic challenges remain, and limited surveillance data of sufficient granularity are available to characterize epidemiological profiles and disease dynamics of the virus. METHODS: An ongoing and long-standing cross-sectional study of acute undifferentiated febrile illness (AUFI) in Cambodia was leveraged to describe the disease epidemiology and characterize the clinical presentation of patients diagnosed with CHIKV during the 2020 outbreak. Participants presenting with AUFI symptoms at ten study locations provided acute and convalescent blood samples and were tested for CHIKV using a reverse transcription-polymerase chain reaction (RT-PCR) and serological diagnostic methods including IgM and IgG. Acute and follow-up clinical data were also collected. RESULTS: From 1194 participant blood samples tested, 331 (27.7%) positive CHIKV cases were detected. Most CHIKV positive individuals (280, 84.6%) reported having a fever 3 to 4 days prior to visiting a health facility. Symptoms including chills, joint pain, nausea, vomiting, and lesions were all statistically significant among CHIKV positive participants compared to CHIKV negative AUFI participants. Cough was negatively associated with CHIKV positive participants. Positivity proportions were significantly higher among adults compared to children. No significant difference was found in positivity proportion between rainy and dry seasons during the outbreak. Positive CHIKV cases were detected in all study site provinces, with the highest test positivity proportion recorded in the rural northeast province of Kratie. CONCLUSIONS: Surveillance data captured in this study provided a clinical and epidemiological characterization of positive CHIKV patients presenting at selected health facilities in Cambodia in 2020, and highlighted the widespread distribution of the outbreak, impacting both urban and rural locations. Findings also illustrated the importance of utilizing both RT-PCR and serological testing for effective CHIKV surveillance.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Adulto , Criança , Humanos , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Estudos Transversais , Camboja/epidemiologia , Anticorpos Antivirais , Vírus Chikungunya/genética , Surtos de Doenças , Febre/epidemiologia , Febre/etiologia
9.
Mil Med ; 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36583720

RESUMO

INTRODUCTION: We present a real-world experience of a U.S. Navy Hospital Ship deployed amid a global Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surge and the challenges of navigating policy while maintaining a mission-focused itinerary in an operational environment. MATERIALS AND METHODS: We performed a chart review of SARS-CoV-2 cases from April 18 to September 20, 2022, within a closed population of fully vaccinated adults onboard the USNS Mercy (T-AH 19) during the 5-month 2022 Pacific Partnership mission to Guam, Vietnam, Palau, Philippines, and the Solomon Islands. RESULTS: There were 123 total SARS-CoV-2 cases over the course of the mission, constituting 16.6% of the total crew (123/741). No more than 14 service members were actively infected at a given time (1.9%, 14/741). The average number of active cases at any given time was 0.8 (1.9 SD, 0.1% [0.8/741]), and just 14 of these were shipboard secondary cases. No significant operational requirements of the ship were impacted by infection-related manning shortages, there were no hospitalizations, and all infected members experienced full recovery. CONCLUSIONS: Despite ongoing cases throughout the majority of the mission, a healthy immunized crew experienced no serious cases and minimal impact on operational effectiveness.

10.
Cureus ; 14(12): e32565, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36540318

RESUMO

The rapid ultrasound for shock and hypotension (RUSH) protocol is a useful tool used in the emergency department (ED) when addressing the severity and etiology of shock. It was designed to be performed in under two minutes with evaluation of the pump (heart), tank (inferior vena cava, thoracic and abdominal compartments) and the pipes (large arteries and veins). However, its application or one similar should extend beyond the ED and into the hospital floor. Here we present an 80-year-old gentleman with a history of atrial fibrillation (A-Fib) on anticoagulation who arrived at the ED due to an episode of pre-syncope just prior to arrival. Initial EKG is concerning for A-Fib with rapid ventricular response (RVR) with a rate in the 130s. After fluid resuscitation patient improved and he was admitted to the telemetry floor for further cardiac workup and cardiology consultation. While waiting for a room in the ED, patient became hypotensive, diaphoretic and pale. After complaining of lower abdominal pain, the ED physician performed a RUSH which showed an abdominal aorta of 8 cm concerning for dissection. Diagnosis was confirmed with CT angiography of the abdomen and he was taken to the OR with successful repair of the abdominal aortic aneurysm (AAA). Patient made meaningful recovery and was discharged to in-patient rehab. The patient described in this vignette was delayed in the ED due to lack of beds on the floor. This allowed for quick ultrasound work-up by the ED physician which led to immediate recognition of the AAA and immediate response by the vascular surgery team. Should this patient have been on the hospital floor, it is unclear if such prompt steps would have occurred prior to patient's further hemodynamic demise.

11.
Cureus ; 14(11): e31125, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36382314

RESUMO

Myocarditis has been a rare, but well-documented side effect of the mRNA-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as a complication of viral infections including SARS-CoV-2. However, myopericarditis as a complication of monoclonal antibody infusion or as a complication of allergic reaction to antibody infusions might be underreported. We report the case of a 30-year-old man with a previous diagnosis of coronavirus disease 2019 (COVID-19) infection one week prior to presentation, unvaccinated for SARS-CoV-2, who was referred from a monoclonal infusion center where he received casirivimab/imdevimab and 15 minutes after the infusion began to complain of chills, chest pain, shortness of breath, and was hypotensive. In the infusion center, the patient received epinephrine and diphenhydramine and was directed to the ER, where the patient was febrile, tachycardic, and hypotensive. Initial troponin was 1.91 which peaked at 11.73 and CK-MB which peaked at 21.2. EKG had no ischemic changes. A two-dimensional echocardiogram showed an ejection fraction (EF) of about 45%, with a left ventricular dysfunction and trivial posterior pericardial effusion, and it was diagnosed as myopericarditis. On admission, he was started on full-dose enoxaparin, aspirin, fluid resuscitation, steroids, remdesevir, and bilevel positive airway pressure (BiPap) due to his respiratory compromise. Three days later, with clinical improvement, a repeat echocardiogram showed EF of 65%, with normal ventricular contractility and no pericardial effusion. The patient was discharged home with close cardiology follow-up. Though this could be a simple case of viral myopericarditis with troponinemia secondary to demand-ischemia, the differential should be broadened to complication of monoclonal antibody, given the sudden symptom onset after infusion completion and/or a possible Kounis syndrome. Though there have not been any reported cases of casirivimab/imdevimab causing myopericarditis, adverse cardiac events after monoclonal therapy have been reported mainly in cancer patients receiving monoclonal infusions.

12.
Cureus ; 14(11): e31511, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36408316

RESUMO

Onychophagia is a habitual nail-biting disorder, usually associated with mental or emotional diseases. It affects 20-30% of the population in all age groups. Human bites have the potential to become serious injuries due to high virulence in the human oral flora and may often require hospital admission, antibiotics and even debridement in the operating room. Thus, repetitive nail biting has the potential to be limb-threatening if not treated early and appropriately. We present a 49-year-old Spanish-speaking gentleman, with a past medical history of repetitive nail biting secondary to severe anxiety, major depression disorder, bilateral hand neuropathy secondary to diabetes mellitus (DM) type 2 who was initially admitted to the hospital due to cellulitis of the fingers with suspected osteomyelitis in the right hand. Anxiety was being treated by psychiatrist with paroxetine however, given no improvement and prolonged follow-ups, the primary care physician (PCP) added hydroxyzine and scheduled alprazolam in an attempt to minimize symptoms. Despite these efforts, patient continued with nail biting. On initial physical exam, the patient had a lack of fingernails and multiple wounds at various stages of healing across all digits. The distal and middle phalanges of the third right digit showed increased erythema and swelling and band tightening. Patient was started on broad-spectrum antibiotics. Initial radiography of the right hand was concerning for osteomyelitis which was later confirmed with Magnetic Resonance Imaging (MRI). Infectious disease specialist agreed on a course of cefepime, vancomycin and metronidazole. On admission, hand surgeon did not see a need for amputation and patient was treated conservatively. Due to minimal improvement after six days on IV antibiotics, patient underwent fasciotomy of the flexor compartment of the right middle finger after patient rejected hand surgeon's recommendation for amputation. He was discharged to a skilled nursing facility where he was to continue intravenous antibiotics for an additional four weeks. The vulnerable patient population of South Texas is predominately Hispanic, Spanish-speaking and uninsured. It is imperative to treat psychiatric disorders early to prevent complications, however, given the low numbers of psychiatrists in the Rio Grande Valley and even fewer who speak Spanish it is not unusual to find an appointment in more than six months. In this case, we observe how a trivial everyday behavior can lead to limb-threatening complications if not treated early and appropriately.

13.
Bioorg Med Chem Lett ; 73: 128912, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35907607

RESUMO

We report new mitochondrial uncouplers derived from the conversion of [1,2,5]oxadiazolo[3,4-b]pyrazines to 1H-imidazo[4,5-b]pyrazines. The in situ Fe-mediated reduction of the oxadiazole fragment followed by cyclization gave access to imidazopyrazines in moderate to good yields. A selection of orthoesters also allowed functionalization on the 2-position of the imidazole ring. This method afforded a variety of imidazopyrazine derivatives with varying substitution on the 2, 5 and 6 positions. Our studies suggest that both a 2-trifluoromethyl group and N-methylation are crucial for mitochondrial uncoupling capacity.


Assuntos
Mitocôndrias , Pirazinas , Ciclização , Mitocôndrias/metabolismo , Oxidiazóis/metabolismo , Pirazinas/metabolismo
14.
Nat Commun ; 13(1): 2547, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538071

RESUMO

When charged particles in periodic lattices are subjected to a constant electric field, they respond by oscillating. Here we demonstrate that the magnetic analogue of these Bloch oscillations are realised in a ferromagnetic easy axis chain. In this case, the "particles" undergoing oscillatory motion in the presence of a magnetic field are domain walls. Inelastic neutron scattering reveals three distinct components of the low energy spin-dynamics including a signature Bloch oscillation mode. Using parameter-free theoretical calculations, we are able to account for all features in the excitation spectrum, thus providing detailed insights into the complex dynamics in spin-anisotropic chains.

15.
Sci Rep ; 12(1): 939, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042900

RESUMO

With the advent of highly sensitive real-time PCR, multiple pathogens have been identified from nasopharyngeal swabs of patients with acute respiratory infections (ARIs). However, the detection of microorganisms in the upper respiratory tract does not necessarily indicate disease causation. We conducted a matched case-control study, nested within a broader fever aetiology project, to facilitate determination of the aetiology of ARIs in hospitalised patients in Northeastern Laos. Consenting febrile patients of any age admitted to Xiengkhuang Provincial Hospital were included if they met the inclusion criteria for ARI presentation (at least one of the following: cough, rhinorrhoea, nasal congestion, sore throat, difficulty breathing, and/or abnormal chest auscultation). One healthy control for each patient, matched by sex, age, and village of residence, was recruited for the study. Nasopharyngeal swabs were collected from participants and tested for 33 pathogens by probe-based multiplex real-time RT-PCR (FastTrack Diagnostics Respiratory pathogen 33 kit). Attributable fraction of illness for a given microorganism was calculated by comparing results between patients and controls (= 100 * [OR - 1]/OR) (OR = odds ratio). Between 24th June 2019 and 24th June 2020, 205 consenting ARI patients and 205 matching controls were recruited. After excluding eight pairs due to age mismatch, 197 pairs were included in the analysis. Males were predominant with sex ratio 1.2:1 and children < 5 years old accounted for 59% of participants. At least one potential pathogen was detected in 173 (88%) patients and 175 (89%) controls. ARI in admitted patients were attributed to influenza B virus, influenza A virus, human metapneumovirus (HMPV), and respiratory syncytial virus (RSV) in 17.8%, 17.2%, 7.5%, and 6.5% of participants, respectively. SARS-CoV-2 was not detected in any cases or controls. Determining ARI aetiology in individual patients remains challenging. Among hospitalised patients with ARI symptoms presenting to a provincial hospital in Northeastern Laos, half were determined to be caused by one of several respiratory viruses, in particular influenza A virus, influenza B virus, HMPV, and RSV.


Assuntos
Hospitalização , Infecções por Vírus de RNA , Vírus de RNA/genética , Infecções Respiratórias , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Doença Aguda , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Laos/epidemiologia , Masculino , Infecções por Vírus de RNA/diagnóstico , Infecções por Vírus de RNA/epidemiologia , Infecções por Vírus de RNA/genética , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/genética , Infecções Respiratórias/virologia , Fatores Sexuais
16.
Eur Heart J Cardiovasc Pharmacother ; 8(3): 291-301, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-34351426

RESUMO

AIMS: There is a lack of evidence regarding the benefits of ß-blocker treatment after invasively managed acute myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF). METHODS AND RESULTS: The tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT) trial is a pragmatic, controlled, prospective, randomized, open-label blinded endpoint (PROBE design) clinical trial testing the benefits of ß-blocker maintenance therapy in patients discharged after MI with or without ST-segment elevation. Patients eligible for participation are those managed invasively during index hospitalization (coronary angiography), with LVEF >40%, and no history of heart failure (HF). At discharge, patients will be randomized 1:1 to ß-blocker therapy (agent and dose according to treating physician) or no ß-blocker therapy. The primary endpoint is a composite of all-cause death, non-fatal reinfarction, or HF hospitalization over a median follow-up period of 2.75 years (minimum 2 years, maximum 3 years). Key secondary endpoints include the incidence of the individual components of the primary composite endpoint, the incidence of cardiac death, and incidence of malignant ventricular arrhythmias or resuscitated cardiac arrest. The primary endpoint will be analysed according to the intention-to-treat principle. CONCLUSION: The REBOOT trial will provide robust evidence to guide the prescription of ß-blockers to patients discharged after MI without reduced LVEF.


Assuntos
Infarto do Miocárdio , Disfunção Ventricular Esquerda , Antagonistas Adrenérgicos beta/efeitos adversos , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Estudos Prospectivos , Volume Sistólico , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular Esquerda
17.
Nat Methods ; 18(10): 1259-1264, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34608309

RESUMO

Understanding complex biological systems requires visualizing structures and processes deep within living organisms. We developed a compact adaptive optics module and incorporated it into two- and three-photon fluorescence microscopes, to measure and correct tissue-induced aberrations. We resolved synaptic structures in deep cortical and subcortical areas of the mouse brain, and demonstrated high-resolution imaging of neuronal structures and somatosensory-evoked calcium responses in the mouse spinal cord at great depths in vivo.


Assuntos
Neuroimagem/métodos , Óptica e Fotônica/métodos , Animais , Proteínas de Bactérias , Embrião não Mamífero , Feminino , Proteínas de Fluorescência Verde , Proteínas Luminescentes , Masculino , Camundongos , Peixe-Zebra
18.
Nat Mater ; 20(12): 1650-1656, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34413490

RESUMO

Emergent relativistic quasiparticles in Weyl semimetals are the source of exotic electronic properties such as surface Fermi arcs, the anomalous Hall effect and negative magnetoresistance, all observed in real materials. Whereas these phenomena highlight the effect of Weyl fermions on the electronic transport properties, less is known about what collective phenomena they may support. Here, we report a Weyl semimetal, NdAlSi, that offers an example. Using neutron diffraction, we found a long-wavelength helical magnetic order in NdAlSi, the periodicity of which is linked to the nesting vector between two topologically non-trivial Fermi pockets, which we characterize using density functional theory and quantum oscillation measurements. We further show the chiral transverse component of the spin structure is promoted by bond-oriented Dzyaloshinskii-Moriya interactions associated with Weyl exchange processes. Our work provides a rare example of Weyl fermions driving collective magnetism.

19.
BMJ Open ; 11(8): e050901, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446498

RESUMO

INTRODUCTION: Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by the MERS-CoV. MERS was first reported in the Kingdom of Saudi Arabia in 2012. Every year, the Hajj pilgrimage to Mecca attracts more than two million pilgrims from 184 countries, making it one of the largest annual religious mass gatherings (MGs) worldwide. MGs in confined areas with a high number of pilgrims' movements worldwide continues to elicit significant global public health concerns. MERCURIAL was designed by adopting a seroconversion surveillance approach to provide multiyear evidence of MG-associated MERS-CoV seroconversion among the Malaysian Hajj pilgrims. METHODS AND ANALYSIS: MERCURIAL is an ongoing multiyear prospective cohort study. Every year, for the next 5 years, a cohort of 1000 Hajj pilgrims was enrolled beginning in the 2016 Hajj pilgrimage season. Pre-Hajj and post-Hajj serum samples were obtained and serologically analysed for evidence of MERS-CoV seroconversion. Sociodemographic data, underlying medical conditions, symptoms experienced during Hajj pilgrimage, and exposure to camel and untreated camel products were recorded using structured pre-Hajj and post-Hajj questionnaires. The possible risk factors associated with the seroconversion data were analysed using univariate and multivariate logistic regression. The primary outcome of this study is to better enhance our understanding of the potential threat of MERS-CoV spreading through MG beyond the Middle East. ETHICS AND DISSEMINATION: This study has obtained ethical approval from the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia. Results from the study will be submitted for publication in peer-reviewed journals and presented in conferences and scientific meetings. TRIAL REGISTRATION NUMBER: NMRR-15-1640-25391.


Assuntos
Infecções por Coronavirus , Coronavírus da Síndrome Respiratória do Oriente Médio , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Humanos , Islamismo , Oriente Médio/epidemiologia , Estudos Prospectivos , Arábia Saudita/epidemiologia , Viagem
20.
Sci Adv ; 7(21)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34138738

RESUMO

The observation of quantum criticality in diverse classes of strongly correlated electron systems has been instrumental in establishing ordering principles, discovering new phases, and identifying the relevant degrees of freedom and interactions. At focus so far have been insulators and metals. Semimetals, which are of great current interest as candidate phases with nontrivial topology, are much less explored in experiments. Here, we study the Kondo semimetal CeRu4Sn6 by magnetic susceptibility, specific heat, and inelastic neutron scattering experiments. The power-law divergence of the magnetic Grünesien ratio reveals that, unexpectedly, this compound is quantum critical without tuning. The dynamical energy over temperature scaling in the neutron response throughout the Brillouin zone and the temperature dependence of the static uniform susceptibility, indicate that temperature is the only energy scale in the criticality. Such behavior, which has been associated with Kondo destruction quantum criticality in metallic systems, could be generic in the semimetal setting.

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