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1.
Radiol Med ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017759

RESUMO

We review the etiologies of bowel obstruction in infants and children that can be identified on ultrasound (US) including perforated appendicitis, intussusception, foreign body ingestion, colonic volvulus, intra-abdominal mass lesions, internal hernia, and stricturing inflammatory bowel disease. US can potentially identify the cause of bowel obstruction in these age groups, without the need for additional cross-sectional imaging, and can aid in patient management including interventional and surgical planning. Hence, it is important to be familiar with the sonographic imaging findings of bowel obstruction in infants and children.

2.
Foods ; 13(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38998507

RESUMO

Modifying starch allows for improvements in its properties to enable improved uses in food matrices, bioplastics, and encapsulating agents. In this research, four varieties of native potato starch were modified by acid treatment, enzymatic treatment, and ethanol precipitation, and their physicochemical, structural, thermal, and techno-functional characteristics were analyzed. According to FT-IR analysis, no influence of the modified starches on the chemical groups was observed, and by scanning electron microscopy (SEM), spherical and oval shapes were observed in the acid and enzymatic treatments, with particle sizes between 27 and 36 µm. In particular, the ethanolic precipitation treatment yielded a different morphology with a particle size between 10.9 and 476.3 nm, resulting in a significant decrease in gelatinization temperature (DSC) and more pronounced crystallites (XRD). On the other hand, the enzymatic treatment showed higher values for z-potential (ζ), and the acid treatment showed lower mass loss (TGA). Acid and ethanolic treatments affected the dough properties compared to native starches. The techno-functional properties showed a decrease in the water absorption index, an increase in the water solubility index, and varied swelling power behaviors. In conclusion, the modification of potato starches through acid, enzymatic, and ethanolic precipitation treatments alters their physicochemical properties, such as swelling capacity, viscosity, and thermal stability. This in turn affects their molecular structure, modifying morphology and the ability to form gels, which expands their applications in the food industry to improve textures, stabilize emulsions, and thicken products. Furthermore, these modifications also open new opportunities for the development of bioplastics by improving the biodegradability and mechanical properties of starch-based plastic materials.

3.
Nutrients ; 16(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38999747

RESUMO

BACKGROUND: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. METHODS: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. RESULTS: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). CONCLUSIONS: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.


Assuntos
COVID-19 , Exercício Físico , Nível de Saúde , Estilo de Vida , Síndrome Metabólica , Autorrelato , Humanos , Masculino , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pessoa de Meia-Idade , Idoso , Espanha/epidemiologia , Síndrome Metabólica/epidemiologia , Fatores Sexuais , Fatores de Risco Cardiometabólico , SARS-CoV-2 , Quarentena , Dieta Mediterrânea/estatística & dados numéricos , Sono , Dieta
4.
mBio ; : e0072124, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958446

RESUMO

Vibrio cholerae is a Gram-negative gastrointestinal pathogen responsible for the diarrheal disease cholera. Expression of key virulence factors, cholera toxin and toxin-coregulated pilus, is regulated directly by ToxT and indirectly by two transmembrane transcription regulators (TTRs), ToxR and TcpP, that promote the expression of toxT. TcpP abundance and activity are controlled by TcpH, a single-pass transmembrane protein, which protects TcpP from a two-step proteolytic process known as regulated intramembrane proteolysis (RIP). The mechanism of TcpH-mediated protection of TcpP represents a major gap in our understanding of V. cholerae pathogenesis. The absence of tcpH leads to unimpeded degradation of TcpP in vitro and a colonization defect in a neonate mouse model of V. cholerae colonization. Here, we show that TcpH protects TcpP from RIP via direct interaction. We also demonstrate that α-linolenic acid, a dietary fatty acid, promotes TcpH-dependent inhibition of RIP via co-association of TcpP and TcpH molecules within detergent-resistant membranes (DRMs) in a mechanism requiring the TcpH transmembrane domain. Taken together, our data support a model where V. cholerae cells use exogenous α-linolenic acid to remodel the phospholipid bilayer in vivo, leading to co-association of TcpP and TcpH within DRMs where RIP of TcpP is inhibited by TcpH, thereby promoting V. cholerae pathogenicity. IMPORTANCE: Vibrio cholerae continues to pose a significant global burden on health and an alternative therapeutic approach is needed, due to evolving multidrug resistance strains. Transcription of toxT, stimulated by TcpP and ToxR, is essential for V. cholerae pathogenesis. Our results show that TcpP, one of the major regulators of toxT gene expression, is protected from proteolysis by TcpH, via direct interaction. Furthermore, we identified a gut metabolite, α-linolenic acid, that stimulates the co-association of TcpP and TcpH within detergent-resistant membranes (also known as lipid-ordered membrane domains), thereby supporting TcpH-dependent antagonism of TcpP proteolysis. Data presented here extend our knowledge of RIP, virulence gene regulation in V. cholerae, and, to the best of our knowledge, provides the first evidence that lipid-ordered membranes exist within V. cholerae. The model presented here also suggests that TTRs, common among bacteria and archaea, and co-component signal transduction systems present in Enterobacteria, could also be influenced similarly.

5.
mBio ; : e0166724, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037272

RESUMO

Severe COVID-19 has been associated with coinfections with bacterial and fungal pathogens. Notably, patients with COVID-19 who develop Staphylococcus aureus bacteremia exhibit higher rates of mortality than those infected with either pathogen alone. To understand this clinical scenario, we collected and examined S. aureus blood and respiratory isolates from a hospital in New York City during the early phase of the pandemic from both SARS-CoV-2+ and SARS-CoV-2- patients. Whole genome sequencing of these S. aureus isolates revealed broad phylogenetic diversity in both patient groups, suggesting that SARS-CoV-2 coinfection was not associated with a particular S. aureus lineage. Phenotypic characterization of the contemporary collection of S. aureus isolates from SARS-CoV-2+ and SARS-CoV-2- patients revealed no notable differences in several virulence traits examined. However, we noted a trend toward overrepresentation of S. aureus bloodstream strains with low cytotoxicity in the SARS-CoV-2+ group. We observed that patients coinfected with SARS-CoV-2 and S. aureus were more likely to die during the acute phase of infection when the coinfecting S. aureus strain exhibited high or low cytotoxicity. To further investigate the relationship between SARS-CoV-2 and S. aureus infections, we developed a murine coinfection model. These studies revealed that infection with SARS-CoV-2 renders mice susceptible to subsequent superinfection with low cytotoxicity S. aureus. Thus, SARS-CoV-2 infection sensitizes the host to coinfections, including S. aureus isolates with low intrinsic virulence. IMPORTANCE: The COVID-19 pandemic has had an enormous impact on healthcare across the globe. Patients who were severely infected with SARS-CoV-2, the virus causing COVID-19, sometimes became infected with other pathogens, which is termed coinfection. If the coinfecting pathogen is the bacterium Staphylococcus aureus, there is an increased risk of patient death. We collected S. aureus strains that coinfected patients with SARS-CoV-2 to study the disease outcome caused by the interaction of these two important pathogens. We found that both in patients and in mice, coinfection with an S. aureus strain lacking toxicity resulted in more severe disease during the early phase of infection, compared with infection with either pathogen alone. Thus, SARS-CoV-2 infection can directly increase the severity of S. aureus infection.

8.
J Colloid Interface Sci ; 672: 256-265, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38838633

RESUMO

HYPOTHESIS: Understanding the digestion of lipid-based pharmaceutical formulations and food systems is necessary for optimising drug and nutrient delivery and has been extensively studied in bulk emulsion systems using the pH-stat method [1]. However, this approach is not suitable for investigation of individual lipid droplets, in particular the interface where the lipase acts. Microfluidic approaches to study digestion at lipid-water interfaces using droplet trapping have been proposed, however the aqueous phase in that case washes over the interface presenting uncertainty over the stoichiometry of interactions [2]. The internal interface of a Janus-like droplet, containing distinct aqueous and lipid compartments, mimics the interface of a lipid droplet in aqueous solution with controlled stoichiometry [3]. Hence, it was hypothesised that the internal interface of Janus droplets can offer a precise way to study the enzymatic digestion of lipids formulations. EXPERIMENTS: Using microfluidic methods, Janus-like droplets were formed by coalescing emulsion droplets containing lipid formulation and pancreatic lipase. Polarised light microscopy (PLM) and in-situ small-angle X-ray scattering (SAXS) were used to investigate the droplets. FINDINGS: PLM revealed the growth of an aligned inverse hexagonal phase (H2), and with SAXS showed that this phase transformation and alignment resulted from enzymatic digestion. A subsequent partial transformation from H2 to inverse bicontinuous cubic phase occurred when simulated intestinal fluid was used instead of Tris buffer. Suggesting that phospholipids and bile salts could diffuse across the internal interface to locally affect their surroundings.


Assuntos
Lipase , Lipase/química , Lipase/metabolismo , Transição de Fase , Emulsões/química , Tamanho da Partícula , Espalhamento a Baixo Ângulo , Gotículas Lipídicas/química , Gotículas Lipídicas/metabolismo , Lipídeos/química , Difração de Raios X , Propriedades de Superfície
9.
Artigo em Inglês | MEDLINE | ID: mdl-38823476

RESUMO

OBJECTIVE: Racial disparities in diagnosis and treatment are prevalent in child psychiatry, including disparate diagnosis rates of internalizing and externalizing disorders in Black and White children. However, limited research has investigated mechanisms that contribute to these disparities. This study examined child racial implicit associations in psychiatric clinicians and medical students to address this gap. METHOD: Psychiatrists and trainees completed an online survey including 2 race Implicit Association Tests (IATs) pairing child faces to words with either positive or negative valence, and words related to internalizing or externalizing behavioral problems. We further investigated psychiatrists' and trainees' demographic predictors of implicit associations. RESULTS: Data were analyzed from 235 psychiatrists and trainees (112 child and adolescent psychiatrists and fellows) who met inclusion criteria. Psychiatrists and trainees demonstrated greater moderate-to-strong association between Black child faces and "bad" words (44.3%) vs "good" words (6.4%), and between externalizing words (41.7%) and internalizing words (7.2%). Psychiatrists' and trainees' demographic characteristics including being female (ß = -0.12; 95% CI = -0.23 to -0.01; p < .05), Black (ß = -0.36; 95% CI = -0.54 to -0.18; p < .001), or an attending physician (ß = -0.26; 95% CI = -0.45 to -0.06; p = .01) were significant predictors of decreased association between Black child faces and negative valence words. Being female was a significant predictor of decreased association between Black child faces and externalizing words (ß = -0.26; 95% CI = -0.45 to -0.06; p = .01). CONCLUSION: Participating psychiatrists and trainees demonstrated bias toward associating Black rather than White child faces with negative words and externalizing behavioral problems. Future research should examine the following: (1) racial implicit associations in a more generalizable sample, (2) the relationship between race IATs and provider behavior, and (3) interventions to reduce racial inequities in psychiatry, including individual and systemic solutions. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science.

10.
Nat Commun ; 15(1): 5417, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926389

RESUMO

Immunological diseases are typically heterogeneous in clinical presentation, severity and response to therapy. Biomarkers of immune diseases often reflect this variability, especially compared to their regulated behaviour in health. This leads to a common difficulty that frustrates biomarker discovery and interpretation - namely, unequal dispersion of immune disease biomarker expression between patient classes necessarily limits a biomarker's informative range. To solve this problem, we introduce dataset restriction, a procedure that splits datasets into classifiable and unclassifiable samples. Applied to synthetic flow cytometry data, restriction identifies biomarkers that are otherwise disregarded. In advanced melanoma, restriction finds biomarkers of immune-related adverse event risk after immunotherapy and enables us to build multivariate models that accurately predict immunotherapy-related hepatitis. Hence, dataset restriction augments discovery of immune disease biomarkers, increases predictive certainty for classifiable samples and improves multivariate models incorporating biomarkers with a limited informative range. This principle can be directly extended to any classification task.


Assuntos
Biomarcadores , Melanoma , Humanos , Biomarcadores/metabolismo , Melanoma/imunologia , Melanoma/genética , Citometria de Fluxo , Imunoterapia/métodos , Doenças do Sistema Imunitário/imunologia
11.
ACS Sens ; 9(6): 3105-3114, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38753893

RESUMO

Rapid detection of microbes is a key feature for monitoring food quality. Unfortunately, current detection systems rely on labor-intensive and time-consuming lab-based processes that are not suitable for point-of-interest applications and typically require several days before results are available. Here, we demonstrate a microfluidic system capable of rapidly concentrating, fluorescent staining, and detecting bacteria in unprocessed complex biological media such as milk. This concentration is done using a surface acoustic wave-driven microfluidic device which operates based on the Bjerknes force, a force generated on one particle by another in its close proximity. We exploit this effect by exciting a tightly packed bed of 50 µm polystyrene microparticles temporarily with surface acoustic waves within a microfluidic device to capture and release bacterial cells on demand. The bacterial cells are fluorescently stained during capture and then detected using fluorescence microscopy upon release. This device offers a high capturing efficiency (>80%) and a 34 Colony Forming Units (CFU)/mL limit of detection, which is 1 order of magnitude below that of plate counting at 30 CFU per standard 100 µL plate (or 300 CFU/mL). This can be attained in just 1 h of processing at 10 µL/min. With this system, we demonstrate that bacterial detection from extremely low concentration samples down to the order of ∼10 CFU/mL is possible without requiring any additional external pre- or postprocessing.


Assuntos
Leite , Leite/microbiologia , Animais , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Som , Bactérias/isolamento & purificação , Poliestirenos/química
12.
Lancet ; 403(10445): 2747-2750, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38795713

RESUMO

The Dobbs v Jackson Women's Health Organization Supreme Court decision, which revoked the constitutional right to abortion in the USA, has impacted the national medical workforce. Impacts vary across states, but providers in states with restrictive abortion laws now must contend with evolving legal and ethical challenges that have the potential to affect workforce safety, mental health, education, and training opportunities, in addition to having serious impacts on patient health and far-reaching societal consequences. Moreover, Dobbs has consequences on almost every facet of the medical workforce, including on physicians, nurses, pharmacists, and others who work within the health-care system. Comprehensive research is urgently needed to understand the wide-ranging implications of Dobbs on the medical workforce, including legal, ethical, clinical, and psychological dimensions, to inform evidence-based policies and standards of care in abortion-restrictive settings. Lessons from the USA might also have global relevance for countries facing similar restrictions on reproductive care.


Assuntos
Decisões da Suprema Corte , Feminino , Humanos , Gravidez , Aborto Induzido/legislação & jurisprudência , Aborto Induzido/ética , Aborto Legal/legislação & jurisprudência , Pessoal de Saúde , Mão de Obra em Saúde , Estados Unidos , Saúde da Mulher
14.
bioRxiv ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38766195

RESUMO

Depletion of microbiota increases susceptibility to gastrointestinal colonization and subsequent infection by opportunistic pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). How the absence of gut microbiota impacts the evolution of MRSA is unknown. The present report used germ-free mice to investigate the evolutionary dynamics of MRSA in the absence of gut microbiota. Through genomic analyses and competition assays, we found that MRSA adapts to the microbiota-free gut through sequential genetic mutations and structural changes that enhance fitness. Initially, these adaptations increase carbohydrate transport; subsequently, evolutionary pathways largely diverge to enhance either arginine metabolism or cell wall biosynthesis. Increased fitness in arginine pathway mutants depended on arginine catabolic genes, especially nos and arcC, which promote microaerobic respiration and ATP generation, respectively. Thus, arginine adaptation likely improves redox balance and energy production in the oxygen-limited gut environment. Findings were supported by human gut metagenomic analyses, which suggest the influence of arginine metabolism on colonization. Surprisingly, these adaptive genetic changes often reduced MRSA's antimicrobial resistance and virulence. Furthermore, resistance mutation, typically associated with decreased virulence, also reduced colonization fitness, indicating evolutionary trade-offs among these traits. The presence of normal microbiota inhibited these adaptations, preserving MRSA's wild-type characteristics that effectively balance virulence, resistance, and colonization fitness. The results highlight the protective role of gut microbiota in preserving a balance of key MRSA traits for long-term ecological success in commensal populations, underscoring the potential consequences on MRSA's survival and fitness during and after host hospitalization and antimicrobial treatment.

15.
bioRxiv ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38746361

RESUMO

RATIONALE: Asthma is a chronic inflammatory disease of the airways that involves crosstalk between myeloid-derived regulatory cells (MDRCs) and CD4+ T cells. Although small extracellular vesicles (sEVs) are known to mediate cell-cell communication, the role of sEV signaling via mitochondria in perpetuating asthmatic airway inflammation is unknown. OBJECTIVES: We investigated the effects of MDRC-derived exosomes on dysregulated T cell responses in asthmatics. METHODS: Small extracellular vesicles isolated from bronchoalveolar lavage fluid or airway MDRCs of mild to moderate asthmatics or healthy controls were co-cultured with autologous peripheral and airway CD4+ T lymphocytes. sEV internalization, sEV-mediated transfer of mitochondria targeted GFP to T cells, sEV mitochondrial signaling, and subsequent activation, proliferation and polarization of CD4+ T lymphocytes to Th1, Th2 and Th17 subsets were assessed. MEASUREMENTS AND MAIN RESULTS: Airway MDRC-derived sEVs from asthmatics mediated T cell receptor engagement and transfer of mitochondria that induced antigen-specific activation and polarization into Th17 and Th2 cells, drivers of chronic airway inflammation in asthma. CD4+ T cells internalized sEVs containing mitochondria predominantly by membrane fusion, and blocking mitochondrial oxidant signaling in MDRC-derived exosomes mitigated T cell activation. Reactive oxygen species-mediated signaling that elicited T cell activation in asthmatics was sEV-dependent. A Drp1-dependent mitochondrial fission in pro-inflammatory MDRCs promoted mitochondrial packaging within sEVs, which then co-localized with the polarized actin cytoskeleton and mitochondrial networks in the organized immune synapse of recipient T cells. CONCLUSIONS: Our studies indicate a previously unrecognized role for mitochondrial fission and exosomal mitochondrial transfer in dysregulated T cell activation and Th cell differentiation in asthma which could constitute a novel therapeutic target.

16.
Lancet ; 403(10445): 2751-2754, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38795714

RESUMO

On June 24, 2022, the US Supreme Court's decision in Dobbs v Jackson Women's Health Organization marked the removal of the constitutional right to abortion in the USA, introducing a complex ethical and legal landscape for patients and providers. This shift has had immediate health and equity repercussions, but it is also crucial to examine the broader impacts on states, health-care systems, and society as a whole. Restrictions on abortion access extend beyond immediate reproductive care concerns, necessitating a comprehensive understanding of the ruling's consequences across micro and macro levels. To mitigate potential harm, it is imperative to establish a research agenda that informs policy making and ensures effective long-term monitoring and reporting, addressing both immediate and future impacts.


Assuntos
Decisões da Suprema Corte , Saúde da Mulher , Humanos , Feminino , Estados Unidos , Gravidez , Saúde da Mulher/legislação & jurisprudência , Acessibilidade aos Serviços de Saúde/legislação & jurisprudência , Direitos da Mulher/legislação & jurisprudência , Aborto Legal/legislação & jurisprudência , Aborto Induzido/legislação & jurisprudência , Aborto Induzido/ética
17.
Addict Behav ; 156: 108073, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38821009

RESUMO

The present systematic review aims to identify electronic interventions for addressing substance use and understand their effectiveness in primary care settings. A systematic search was carried out in the Web of Science, PubMed/MEDLINE, Scopus, and Cochrane Library. The search included the keywords "electronic intervention", "substance use", "primary care" and synonyms. To determine the quality and recommendation of the analyzed interventions, the efficacy results reported by the studies were considered, as well as the Mixed Methods Appraisal Tool (MMAT) assessment and the GRADE Evidence Assessment. Twenty-one electronic interventions in Primary Care were identified: internet, mobile or tablet applications, text messages, emails, automated telephone calls, or electronic self-reports. These interventions had diverse components, incorporating theories that have proven effective in face-to-face interventions as their theoretical frameworks. Some of them were complementary to in-person treatment, while others replaced it. Six interventions (28.5 %) displayed high quality: HealthCall, AB-CASI, Quit Genius, eCHECKUP-TOGO, CBI, and TES. Another nine interventions (42.8 %) were found to have moderate-high quality: Alcohol y Salud, IVR-BI, Program of Wallace et al., Let's Talk About Smoking, SMSalud, ESCAPE, AAC-ASPIRE, iQuit, and Programa VIH. One intervention (4.7 %) had moderate-low quality: Vive sin tabaco ¡Decídete! The remaining five interventions (23.8 %) were found to have very low quality: Connection to health, cSBI, Teen Well Check, the program of Helzer et al. (2008), and Down your drink. The programs with the highest recommendation for addressing alcohol-related issues are HealthCall and AB-CASI; for tobacco use, it is Quit Genius; for cannabis use, it is eCHECKUP-TOGO; for addressing both legal and illegal substances, it is CBI and TES. Finally, for specific illicit drug use, the only recommended program is CBI. This last intervention, CBI, is of the highest quality and, therefore, can be considered a model intervention for dissemination in the primary care setting.


Assuntos
Atenção Primária à Saúde , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/terapia , Envio de Mensagens de Texto , Telemedicina , Internet , Aplicativos Móveis , Correio Eletrônico
18.
Curr Biol ; 34(12): 2712-2718.e3, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38806055

RESUMO

New World porcupines (Erethizontinae) originated in South America and dispersed into North America as part of the Great American Biotic Interchange (GABI) 3-4 million years ago.1 Extant prehensile-tailed porcupines (Coendou) today live in tropical forests of Central and South America.2,3 In contrast, North American porcupines (Erethizon dorsatum) are thought to be ecologically adapted to higher-latitude temperate forests, with a larger body, shorter tail, and diet that includes bark.4,5,6,7 Limited fossils8,9,10,11,12,13 have hindered our understanding of the timing of this ecological differentiation relative to intercontinental dispersal during the GABI and expansion into temperate habitats.14,15,16,17,18 Here, we describe functionally important features of the skeleton of the extinct Erethizon poyeri, the oldest nearly complete porcupine skeleton documented from North America, found in the early Pleistocene of Florida. It differs from extant E. dorsatum in having a long, prehensile tail, grasping foot, and lacking dental specializations for bark gnawing, similar to tropical Coendou. Results from phylogenetic analysis suggest that the more arboreal characteristics found in E. poyeri are ancestral for erethizontines. Only after it expanded into temperate, Nearctic habitats did Erethizon acquire the characteristic features that it is known for today. When combined with molecular estimates of divergence times, results suggest that Erethizon was ecologically similar to a larger species of Coendou when it crossed the Isthmus of Panama by the early Pleistocene. It is likely that the range of this more tropically adapted form was limited to a continuous forested biome that extended from South America through the Gulf Coast.


Assuntos
Fósseis , Porcos-Espinhos , Porcos-Espinhos/anatomia & histologia , Animais , Fósseis/anatomia & histologia , América do Sul , Cauda/anatomia & histologia , Extinção Biológica , América do Norte , Evolução Biológica , Ecossistema
19.
Nat Commun ; 15(1): 4494, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802368

RESUMO

Efflux pump antiporters confer drug resistance to bacteria by coupling proton import with the expulsion of antibiotics from the cytoplasm. Despite efforts there remains a lack of understanding as to how acid/base chemistry drives drug efflux. Here, we uncover the proton-coupling mechanism of the Staphylococcus aureus efflux pump NorA by elucidating structures in various protonation states of two essential acidic residues using cryo-EM. Protonation of Glu222 and Asp307 within the C-terminal domain stabilized the inward-occluded conformation by forming hydrogen bonds between the acidic residues and a single helix within the N-terminal domain responsible for occluding the substrate binding pocket. Remarkably, deprotonation of both Glu222 and Asp307 is needed to release interdomain tethering interactions, leading to opening of the pocket for antibiotic entry. Hence, the two acidic residues serve as a "belt and suspenders" protection mechanism to prevent simultaneous binding of protons and drug that enforce NorA coupling stoichiometry and confer antibiotic resistance.


Assuntos
Proteínas de Bactérias , Microscopia Crioeletrônica , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Prótons , Staphylococcus aureus , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Staphylococcus aureus/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/química , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Antibacterianos/química , Modelos Moleculares , Transporte Biológico , Sítios de Ligação , Ligação de Hidrogênio , Conformação Proteica
20.
Toxins (Basel) ; 16(5)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38787073

RESUMO

Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in adolescents with CM; (2) to review the literature on BTX-A use in the pediatric population. This prospective observational study included patients under 18 years old with CM treated with BTX-A (PREEMPT protocol) as compassionate use. Demographic, efficacy (monthly headache days-MHD; monthly migraine days-MMD; acute medication days/month-AMDM) and side effect data were collected. A ≥ 50% reduction in MHD was considered as a response. Effectiveness and safety were analyzed at 6 and 12 months. A systematic review of the use of BTX-A in children/adolescents was conducted in July 2023. In total, 20 patients were included (median age 15 years [14.75-17], 70% (14/20) females). The median basal frequencies were 28.8 [20-28] MHD, 18 [10-28] MMD and 10 [7.5-21.2] AMDM. Compared with baseline, at 6 months (n = 20), 11 patients (55%) were responders, with a median reduction in MHD of -20 days/month (p = 0.001). At 12 months (n = 14), eight patients (57.1%) were responders, with a median reduction in MHD of -17.5 days/month (p = 0.002). No adverse effects were reported. The literature search showed similar results. Our data supports the concept that BTX-A is effective, well tolerated, and safe in adolescents with CM resistant to oral preventatives.


Assuntos
Toxinas Botulínicas Tipo A , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , Toxinas Botulínicas Tipo A/efeitos adversos , Adolescente , Feminino , Masculino , Estudos Prospectivos , Doença Crônica , Resultado do Tratamento , Fármacos Neuromusculares/uso terapêutico , Fármacos Neuromusculares/efeitos adversos
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