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1.
Immunity ; 56(6): 1239-1254.e7, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37028427

RESUMO

Early-life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here, we showed that tolerance in skin was controlled by microbial interaction with a specialized subset of antigen-presenting cells. More particularly, CD301b+ type 2 conventional dendritic cells (DCs) in neonatal skin were specifically capable of uptake and presentation of commensal antigens for the generation of regulatory T (Treg) cells. CD301b+ DC2 were enriched for phagocytosis and maturation programs, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early-life DC subsets, neonatal CD301b+ DC2 highly expressed the retinoic-acid-producing enzyme, RALDH2, the deletion of which limited commensal-specific Treg cell generation. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early-life tolerance at the cutaneous interface.


Assuntos
Células Dendríticas , Pele , Animais , Camundongos , Humanos , Linfócitos T Reguladores , Tolerância Imunológica , Aldeído Oxirredutases/metabolismo
2.
CA Cancer J Clin ; 70(5): 355-374, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32813307

RESUMO

The management of human epidermal growth factor receptor (HER2)-positive breast cancer (BC) has rapidly evolved over the last 20 years. Major advances have led to US Food and Drug Administration approval of 7 HER2-targeted therapies for the treatment of early-stage and/or advanced-stage disease. Although oncologic outcomes continue to improve, most patients with advanced HER2-positive BC ultimately die of their disease because of primary or acquired resistance to therapy, and patients with HER2-positive early BC who have residual invasive disease after preoperative systemic therapy are at a higher risk of distant recurrence and death. The concept of treatment de-escalation and escalation is increasingly important to optimally tailor therapy for patients with HER2-positive BC and is a major focus of the current review. Research efforts in this regard are discussed as well as updates regarding the evolving standard of care in the (neo)adjuvant and metastatic settings, including the use of novel combination therapies. The authors also briefly discuss ongoing challenges in the management of HER2-positive BC (eg, intrinsic vs acquired drug resistance, the identification of predictive biomarkers, the integration of imaging techniques to guide clinical practice), and the treatment of HER2-positive brain metastases. Research aimed at superseding these challenges will be imperative to ensure continued progress in the management of HER2-positive BC going forward.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Receptor ErbB-2/metabolismo , Antineoplásicos/uso terapêutico , Biomarcadores/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Humanos , Imagem Molecular , Padrão de Cuidado
3.
Biophys J ; 123(16): 2443-2454, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38872310

RESUMO

Cells intricately sense mechanical forces from their surroundings, driving biophysical and biochemical activities. This mechanosensing phenomenon occurs at the cell-matrix interface, where mechanical forces resulting from cellular motion, such as migration or matrix stretching, are exchanged through surface receptors, primarily integrins, and their corresponding matrix ligands. A pivotal player in this interaction is the α5ß1 integrin and fibronectin (FN) bond, known for its role in establishing cell adhesion sites for migration. However, upregulation of the α5ß1-FN bond is associated with uncontrolled cell metastasis. This bond operates through catch bond dynamics, wherein the bond lifetime paradoxically increases with greater force. The mechanism sustaining the characteristic catch bond dynamics of α5ß1-FN remains unclear. Leveraging molecular dynamics simulations, our approach unveils a pivot-clip mechanism. Two key binding sites on FN, namely the synergy site and the RGD (Arg-Gly-Asp) motif, act as active points for structural changes in α5ß1 integrin. Conformational adaptations at these sites are induced by a series of hydrogen bond formations and breaks at the synergy site. We disrupt these adaptations through a double mutation on FN, known to reduce cell adhesion. A whole-cell finite-element model is employed to elucidate how the synergy site may promote dynamic α5ß1-FN binding, resisting cell contraction. In summary, our study integrates molecular- and cellular-level modeling to propose that FN's synergy site reinforces cell adhesion through enhanced binding dynamics and a mechanosensitive pivot-clip mechanism. This work sheds light on the interplay between mechanical forces and cell-matrix interactions, contributing to our understanding of cellular behaviors in physiological and pathological contexts.


Assuntos
Adesão Celular , Fibronectinas , Integrina alfa5beta1 , Mecanotransdução Celular , Simulação de Dinâmica Molecular , Integrina alfa5beta1/metabolismo , Fibronectinas/metabolismo , Fibronectinas/química , Sítios de Ligação , Humanos , Ligação Proteica , Oligopeptídeos
4.
Emerg Infect Dis ; 30(8): 1599-1608, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39043406

RESUMO

Bacterial zoonoses are established causes of severe febrile illness in East Africa. Within a fever etiology study, we applied a high-throughput 16S rRNA metagenomic assay validated for detecting bacterial zoonotic pathogens. We enrolled febrile patients admitted to 2 referral hospitals in Moshi, Tanzania, during September 2007-April 2009. Among 788 participants, median age was 20 (interquartile range 2-38) years. We performed PCR amplification of V1-V2 variable region 16S rRNA on cell pellet DNA, then metagenomic deep-sequencing and pathogenic taxonomic identification. We detected bacterial zoonotic pathogens in 10 (1.3%) samples: 3 with Rickettsia typhi, 1 R. conorii, 2 Bartonella quintana, 2 pathogenic Leptospira spp., and 1 Coxiella burnetii. One other sample had reads matching a Neoerhlichia spp. previously identified in a patient from South Africa. Our findings indicate that targeted 16S metagenomics can identify bacterial zoonotic pathogens causing severe febrile illness in humans, including potential novel agents.


Assuntos
Febre , Metagenômica , RNA Ribossômico 16S , Humanos , Tanzânia/epidemiologia , Adulto , Pré-Escolar , Adolescente , Metagenômica/métodos , Febre/microbiologia , Masculino , Feminino , Animais , Criança , RNA Ribossômico 16S/genética , Adulto Jovem , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Zoonoses Bacterianas/microbiologia , Zoonoses Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/diagnóstico , Zoonoses/microbiologia , Zoonoses/epidemiologia
5.
Osteoarthritis Cartilage ; 32(5): 548-560, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38160742

RESUMO

OBJECTIVE: Cartilage tissue engineering strategies that use autologous chondrocytes require in vitro expansion of cells to obtain enough cells to produce functional engineered tissue. However, chondrocytes dedifferentiate during expansion culture, limiting their ability to produce chondrogenic tissue and their utility for cell-based cartilage repair strategies. The current study identified conditions that favor cartilage production and the mechanobiological mechanisms responsible for these benefits. DESIGN: Chondrocytes were isolated from juvenile bovine knee joints and cultured with (primed) or without (unprimed) a growth factor cocktail. Gene expression, cell morphology, cell adhesion, cytoskeletal protein distribution, and cell mechanics were assessed. Following passage 5, cells were embedded into agarose hydrogels to evaluate functional properties of engineered cartilage. RESULTS: Priming cells during expansion culture altered cell phenotype and chondrogenic tissue production. Unbiased ribonucleic acid-sequencing analysis suggested, and experimental studies confirmed, that growth factor priming delays dedifferentiation associated changes in cell adhesion and cytoskeletal organization. Priming also overrode mechanobiological pathways to prevent chondrocytes from remodeling their cytoskeleton to accommodate the stiff, monolayer microenvironment. Passage 1 primed cells deformed less and had lower yes associated protein 1 activity than unprimed cells. Differences in cell adhesion, morphology, and cell mechanics between primed and unprimed cells were mitigated by passage 5. CONCLUSIONS: Priming suppresses mechanobiologic cytoskeletal remodeling to prevent chondrocyte dedifferentiation, resulting in more cartilage-like tissue-engineered constructs.


Assuntos
Cartilagem Articular , Condrócitos , Animais , Bovinos , Condrócitos/metabolismo , Células Cultivadas , Cartilagem , Engenharia Tecidual/métodos , Condrogênese , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
6.
Sex Health ; 212024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38801749

RESUMO

Background Launched in 2016 by Prevention Access Campaign, the 'Undetectable=Untransmittable' (U=U) campaign empowers people living with HIV to live full social, sexual and reproductive lives, dismantle stigma, promote increased treatment access, and advocate for updated HIV guidelines. Methods Key priorities for promoting improvements to community-centred, evidence-informed U=U policy and research were the focus of a half-day global roundtable held in 2023 alongside the 12th International AIDS Society Conference in Brisbane, Australia. After a series of presentations, experts in U=U research, policymaking, advocacy and HIV clinical care participated in facilitated discussions, and detailed notes were taken on issues related to advancing U=U policy and research. Results Expert participants shared that knowledge and trust in U=U remains uneven, and is largely concentrated among people living with HIV, particularly those connected to gay and bisexual networks. It was agreed that there is a need to ensure all members of priority populations are explicitly included in U=U policies that promote U=U. Participants also identified a need for policymakers, healthcare professionals, advocates and researchers to work closely with community-based organisations to ensure the U=U message is relevant, useful, and utilised in the HIV response. Adopting language, such as 'zero risk', was identified as crucial when describing undetectable viral load as an effective HIV prevention strategy. Conclusion U=U can have significant benefits for the mental and physical wellbeing of people living with HIV. There is an urgent need to address the structural barriers to HIV care and treatment access to ensure the full benefits of U=U are realised.


Assuntos
Infecções por HIV , Política de Saúde , Humanos , Infecções por HIV/prevenção & controle , Saúde Global , Estigma Social , Prioridades em Saúde , Acessibilidade aos Serviços de Saúde
7.
J Vet Pharmacol Ther ; 47(4): 252-256, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38557931

RESUMO

Lameness is a significant welfare concern in goats. Amphotericin B is used via intraarticular (IA) administration in models to study experimentally induced lameness in large animals. The main objective of this study was to estimate plasma pharmacokinetic (PK) parameters for amphotericin B in goats after a single IA administration. Liposomal amphotericin B was administered to ten Kiko-cross goats at a dose of 10 mg total (range: 0.34-0.51 mg/kg) via IA administration into the right hind lateral distal interphalangeal joint. Plasma samples were collected over 96 h. Amphotericin B concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive PK parameters. Following single IA administration, maximum plasma concentration was estimated at 54.6 ± 16.5 ng/mL, and time to maximum concentration ranged from 6 to 12 h. Elimination half-life was estimated at 30.9 ± 16.5 h, and mean residence time was 45.1 ± 10.4 h. The volume of distribution after IA administration was 13.3 ± 9.4 L/kg. The area under the curve was 1481 ± 761 h*ng/mL. The achieved maximum concentration was less than the observed concentrations for other species and routes of administration. Further research is needed into the pharmacodynamics of IA liposomal amphotericin B in goats to determine specific research strategies.


Assuntos
Anfotericina B , Área Sob a Curva , Cabras , Animais , Cabras/metabolismo , Anfotericina B/farmacocinética , Anfotericina B/administração & dosagem , Anfotericina B/sangue , Meia-Vida , Injeções Intra-Articulares/veterinária , Masculino , Feminino , Antifúngicos/farmacocinética , Antifúngicos/administração & dosagem , Antifúngicos/sangue
8.
Clin Infect Dis ; 76(3): e540-e543, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35686436

RESUMO

We enrolled arriving international air travelers in a severe acute respiratory syndrome coronavirus 2 genomic surveillance program. We used molecular testing of pooled nasal swabs and sequenced positive samples for sublineage. Traveler-based surveillance provided early-warning variant detection, reporting the first US Omicron BA.2 and BA.3 in North America.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Aeroportos , COVID-19/diagnóstico , Genômica
9.
J Antimicrob Chemother ; 78(12): 2938-2942, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37921335

RESUMO

OBJECTIVES: To characterize HIV drug resistance (HIVDR) below and above the WHO threshold of 1000 copies/mL, considered for the definition of HIV ART failure in resource-limited settings. METHODS: From a cohort of 280 adolescents (aged 10-19 years) receiving ART for at least 6 months, genotypic resistance testing (GRT) was attempted for two groups of participants: participants with low-level viraemia [LLV; viral load (VL) 200-999 copies/mL] and those in virological failure (VF; confirmed VL ≥1000 copies/mL) using an in-house method. The Stanford HIValg Program was used to identify relevant HIVDR mutations and predict the efficacy of the newly introduced tenofovir-lamivudine-dolutegravir combination. RESULTS: GRT was successfully performed in 54/58 (93.1%) eligible participants, of which 28/31 (90.3%) were in VF and 26/27 (96.3%) had LLV. A high level of resistance was found both in adolescents with LLV and those in VF, with respectively 84.6% (22/26) and 75.0% (21/28) of participants harbouring at least one HIVDR mutation. NRTIs and NNRTIs were the most affected drug classes in both population groups. In contrast, PIs were not significantly affected and dolutegravir was expected to be active for all participants tested. However, for the newly introduced dolutegravir-based combination, functional monotherapy (dolutegravir only) was potentially possible for 22.7% (5/22) of the participants with LLV. CONCLUSIONS: Our findings show that the 1000 copies/mL threshold is not an indicator of virological success and we call for a revision of the current WHO definition of VF in resource-limited countries.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Adolescente , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Viremia/tratamento farmacológico , Viremia/epidemiologia , Camarões/epidemiologia , Prevalência , HIV-1/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Carga Viral , Farmacorresistência Viral/genética
10.
MMWR Recomm Rep ; 71(2): 1-8, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36173766

RESUMO

THIS REPORT SUMMARIZES ALL RECOMMENDATIONS FROM CDC'S ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) FOR THE USE OF LYOPHILIZED CVD 103-HGR VACCINE (CVD 103-HGR) (VAXCHORA, EMERGENT BIOSOLUTIONS, GAITHERSBURG, MD) IN THE UNITED STATES. THE LIVE ATTENUATED ORAL CHOLERA VACCINE IS DERIVED FROM: Vibrio cholerae O1 and is administered in a single dose. Cholera is a toxin-mediated bacterial gastrointestinal illness caused by toxigenic V. cholerae serogroup O1 or, uncommonly, O139. Up to 10% of infections manifest as severe cholera (i.e., cholera gravis), profuse watery diarrhea that can cause severe dehydration and death within hours. Fluid replacement therapy can reduce the fatality rate to <1%. Risk factors for cholera gravis include high dose exposure, blood group O, increased gastric pH (e.g., from antacid therapy), and partial gastrectomy. Cholera is rare in the United States, but cases occur among travelers to countries where cholera is endemic or epidemic and associated with unsafe water and inadequate sanitation. Travelers might be at increased risk for poor outcomes from cholera if they cannot readily access medical services or if they have a medical condition that would be worsened by dehydration, such as cardiovascular or kidney disease. This report describes previously published ACIP recommendations about use of CVD 103-HgR for adults aged 18-64 years and introduces a new recommendation for use in children and adolescents aged 2-17 years. ACIP recommends CVD 103-HgR, the only cholera vaccine licensed for use in the United States, for prevention of cholera among travelers aged 2-64 years to an area with active cholera transmission. Health care providers can use these guidelines to develop the pretravel consultation for persons traveling to areas with active cholera transmission.


Assuntos
Vacinas contra Cólera , Cólera , Adolescente , Adulto , Comitês Consultivos , Antiácidos , Antígenos de Grupos Sanguíneos , Criança , Pré-Escolar , Cólera/epidemiologia , Cólera/prevenção & controle , Vacinas contra Cólera/administração & dosagem , Desidratação , Humanos , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Vacinação , Vacinas Atenuadas , Vibrio cholerae O1 , Água , Adulto Jovem
11.
BMC Infect Dis ; 23(1): 217, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024821

RESUMO

BACKGROUND: Cryptococcosis is an increasingly common infection given the growing immunocompromised population worldwide. Cryptococcal antigen (CrAg) testing demonstrates excellent sensitivity and specificity and is the mainstay of diagnosis. However, there may be rare instances in which false-negative CrAg results can delay diagnosis and early treatment, which are critical to ensure positive outcomes. CASE PRESENTATION: A 31-year-old man living with HIV/AIDS who was not taking antiretroviral therapy was hospitalized with fever, diarrhea, and headaches. CD4 count on presentation was 71 cells/uL, and HIV viral load was 3,194,949 copies/mL. Serum CrAg testing was initially negative, however CSF CrAg performed several days later was positive at 1:40 and blood and CSF cultures grew Cryptococcus neoformans. Colonoscopy revealed mucosal papules throughout the sigmoid colon, and tissue biopsy showed yeast within the lamina propria consistent with GI cryptococcosis. Given the high burden of disease, the original serum CrAg specimen was serially diluted and subsequently found to be positive at 1:2,560, confirming the postzone phenomenon. CONCLUSION: Cryptococcosis has a wide array of presentations including intraluminal GI disease, as seen in this patient. While serum CrAg testing displays excellent test characteristics, it is important for clinicians to be aware of the rare instances in which false-negative results may occur in the presence of excess antigen, as in this case.


Assuntos
Síndrome da Imunodeficiência Adquirida , Criptococose , Cryptococcus neoformans , Infecções por HIV , Meningite Criptocócica , Masculino , Humanos , Adulto , Infecções por HIV/complicações , Testes Imunológicos , Antígenos de Fungos
12.
J Biomech Eng ; 144(6)2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35079770

RESUMO

The intervertebral disc is a complex structure that experiences multiaxial stresses regularly. Disc failure through herniation is a common cause of lower back pain, which causes reduced mobility and debilitating pain, resulting in heavy socioeconomic burdens. Unfortunately, herniation etiology is not well understood, partially due to challenges in replicating herniation in vitro. Previous studies suggest that flexion elevated risks of herniation. Thus, the objective of this study was to use a multiscale and multiphasic finite element model to evaluate the risk of failure under torque- or muscle-driven flexion. Models were developed to represent torque-driven flexion with the instantaneous center of rotation (ICR) located on the disc, and the more physiologically representative muscle-driven flexion with the ICR located anterior of the disc. Model predictions highlighted disparate disc mechanics regarding bulk deformation, stress-bearing mechanisms, and intradiscal stress-strain distributions. Specifically, failure was predicted to initiate at the bone-disc boundary under torque-driven flexion, which may explain why endplate junction failure, instead of herniation, has been the more common failure mode observed in vitro. By contrast, failure was predicted to initiate in the posterolateral annulus fibrosus under muscle-driven flexion, resulting in consistent herniation. Our findings also suggested that muscle-driven flexion combined with axial compression could be sufficient for provoking herniation in vitro and in silico. In conclusion, this study provided a computational framework for designing in vitro testing protocols that can advance the assessment of disc failure behavior and the performance of engineered disc implants.


Assuntos
Deslocamento do Disco Intervertebral , Disco Intervertebral , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Disco Intervertebral/fisiologia , Vértebras Lombares , Músculos , Torque
13.
J Exerc Sci Fit ; 20(4): 382-390, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36311171

RESUMO

Background/Objective: The 2022 Philippine Report Card on Physical Activity for Children and Adolescents provides a comprehensive assessment of physical activity and other related behaviors, including the various factors and settings that influence these behaviors. It serves as an advocacy tool to increase awareness of the physical activity situation among children and young people in the country. This article describes the development and results of the first Philippine Report Card on Physical Activity for Children and Adolescents. Methods: Following a systematic process provided by the Active Healthy Kids Global Alliance, a team consisting of 25 sports and physical activity specialists identified and reviewed the best available nationally representative data related to physical activity indicators. These data were then used to inform the grades of the ten (10) physical activity indicators. Results: Sufficient data were identified to assign grades to five (5) indicators: Overall Physical Activity (F), Active Transportation (D), Sedentary Behavior (B), School (C-), and Government (B). Insufficient data existed to assign grades to the remaining five (5) indicators: Organized Sport and Physical Activity, Active Play, Physical Fitness, Family and Peers, and Community and Environment. Conclusion: Despite government policies related to physical activity in the country, the majority of children and adolescents in the Philippines do not meet the recommended amount of physical activity for health. More work is needed to improve the translation of these policies into measurable programs, highlighting the need to create better physical activity opportunities and develop national surveillance mechanisms.

14.
Clin Infect Dis ; 73(11): e4581-e4589, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-33247585

RESUMO

BACKGROUND: Typhoid fever in the United States is acquired primarily through international travel by unvaccinated travelers. There is currently no typhoid vaccine licensed in the United States for use in children <2 years. METHODS: We reviewed Salmonella enterica serotype Typhi infections reported to the Centers for Disease Control and Prevention (CDC) and antimicrobial-resistance data on Typhi isolates in CDC's National Antimicrobial Resistance Monitoring System from 1999 through 2015. RESULTS: 5131 cases of typhoid fever were diagnosed and 5004 Typhi isolates tested for antimicrobial susceptibility. Among 1992 pediatric typhoid fever patients, 1616 (81%) had traveled internationally within 30 days of illness onset, 1544 (81%) of 1906 were hospitalized (median duration, 6 days; range, 0-50), and none died. Forty percent (799) were <6 years old; 12% were <2 years old. Based on age and travel destination, 1435 (83%) of 1722 pediatric patients were vaccine-eligible; only 68 (5%) of 1361 were known to be vaccinated. Of 2003 isolates tested for antimicrobial susceptibility, 1216 (61%) were fluoroquinolone-nonsusceptible, of which 272 (22%) were also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant [MDR]). All were susceptible to ceftriaxone and azithromycin. MDR and fluoroquinolone-nonsusceptible isolates were more common in children than adults (16% vs 9%, P < .001, and 61% vs 54%, P < .001, respectively). Fluoroquinolone nonsusceptibility was more common among travel-associated than domestically acquired cases (70% vs 17%, P < .001). CONCLUSIONS: Approximately 95% of currently vaccine-eligible pediatric travelers were unvaccinated, and antimicrobial-resistant infections were common. New public health strategies are needed to improve coverage with currently licensed vaccines. Introduction of an effective pretravel typhoid vaccine for children <2 years could reduce disease burden and prevent drug-resistant infections.


Assuntos
Febre Tifoide , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/farmacologia , Criança , Pré-Escolar , Humanos , Testes de Sensibilidade Microbiana , Salmonella typhi , Viagem , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia , Estados Unidos/epidemiologia
15.
J Biomech Eng ; 143(8)2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33729477

RESUMO

Painful herniated discs are treated surgically by removing extruded nucleus pulposus (NP) material (nucleotomy). NP removal through enzymatic digestion is also commonly performed to initiate degenerative changes to study potential biological repair strategies. Experimental and computational studies have shown a decrease in disc stiffness with nucleotomy under single loading modalities, such as compression-only or bending-only loading. However, studies that apply more physiologically relevant loading conditions, such as compression in combination with bending or torsion, have shown contradicting results. We used a previously validated bone-disc-bone finite element model (Control) to create a Nucleotomy model to evaluate the effect of dual loading conditions (compression with torsion or bending) on intradiscal deformations. While disc joint stiffness decreased with nucleotomy under single loading conditions, as commonly reported in the literature, dual loading resulted in an increase in bending stiffness. More specifically, dual loading resulted in a 40% increase in bending stiffness under flexion and extension and a 25% increase in stiffness under lateral bending. The increase in bending stiffness was due to an increase and shift in compressive stress, where peak stresses migrated from the NP-annulus interface to the outer annulus. In contrast, the decrease in torsional stiffness was due to greater fiber reorientation during compression. In general, large radial strains were observed with nucleotomy, suggesting an increased risk for delamination or degenerative remodeling. In conclusion, the effect of nucleotomy on disc mechanics depends on the type and complexity of applied loads.


Assuntos
Disco Intervertebral
16.
BMC Health Serv Res ; 21(1): 941, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503508

RESUMO

INTRODUCTION: Despite prioritization, routine antenatal influenza vaccine coverage is < 16% in South Africa. We aimed to describe maternal influenza vaccine coverage in 27 antenatal clinics (ANCs) in Gauteng and Western Cape (WC) Provinces, where in collaboration with the Department of Health (DoH), we augmented the annual influenza vaccination programme among pregnant women. METHODS: From 2015 through 2018, 40,230 additional doses of influenza vaccine were added to the available stock and administered as part of routine antenatal care. Educational talks were given daily and data were collected on women attending ANCs. We compared characteristics of vaccinated and unvaccinated women using multivariable logistic regression. RESULTS: We screened 62,979 pregnant women during the period when Southern Hemisphere influenza vaccines were available (27,068 in Gauteng and 35,911 in WC). Vaccine coverage at the targeted clinics was 78.7% (49,355/62682), although pregnant women in WC were more likely to be vaccinated compared to those in the Gauteng (Odds ratio (OR) =3.7 p < 0.001). Women aged 25-29 and > 35 years were less likely to be vaccinated than women aged 18-24 years (OR = 0.9 p = 0.053; OR = 0.9 p < 0.001). HIV positive status was not associated with vaccination (OR = 1.0 p = 0.266). Reasons for not vaccinating included: vaccine stock-outs where ANCs depleted available stock of vaccines and/or were awaiting delivery of vaccines (54.6%, 6949/12723), refusal/indecision (25.8%, 3285), and current illness that contraindicated vaccination (19.6%, 2489). CONCLUSION: Antenatal vaccination uptake was likely improved by the increased vaccine supply and vaccine education offered during our campaign.


Assuntos
Vacinas contra Influenza , Influenza Humana , Complicações Infecciosas na Gravidez , Feminino , Humanos , Programas de Imunização , Influenza Humana/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes , África do Sul , Vacinação
17.
Rev Sci Tech ; 40(2): 413-420, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34542105

RESUMO

The world is facing a broad range of challenges related to agriculture, and particularly the livestock sector, including threats to productivity, the natural environment and human health. While much research has been conducted into potential risks and their drivers, the 2020 COVID-19 pandemic demonstrated how governments can be affected by shocks that are to some extent predictable but for which they are often ill prepared. Policy seeks to anticipate and also influence the future and, as policy-makers, national Veterinary Services have an important role in both anticipating and influencing the future of their countries and the world. In the first part of this paper, the author summarises a wide range of Foresight methodologies and tools relevant to, or used by, Veterinary Services or veterinary researchers. This discussion is followed by an example of the adaptation and application of a Foresight framework tailored specifically to Veterinary Services. Finally, the author draws conclusions on Foresight methodologies useful to Veterinary Services.


Le monde est confronté à un large éventail de défis en lien avec l'agriculture et plus particulièrement avec le secteur de l'élevage, parmi lesquels figurent les menaces pesant sur la productivité, l'environnement naturel et la santé humaine. Alors même que maints travaux de recherches ont été menés sur les risques potentiels et leurs facteurs déterminants, la pandémie de COVID-19 de 2020 a montré que les gouvernements peuvent être atteints par des chocs qui sont, jusqu'à un certain point, prévisibles, mais auxquels ils sont souvent mal préparés. La politique cherche à anticiper et à influencer l'avenir ; en tant que responsables des politiques à mener, les Services vétérinaires nationaux jouent un rôle majeur aussi bien pour anticiper l'avenir de leur pays et du monde que pour y influer. Dans une première partie, l'auteure décrit brièvement les diverses méthodes et outils de prospective utilisés par les Services vétérinaires ou les chercheurs du secteur vétérinaire, ou qui présentent un intérêt pour eux. Elle examine ensuite l'exemple d'un cadre de prospective qui a été adapté et appliqué dans le but de répondre spécifiquement aux besoins des Services vétérinaires. Enfin, elle tire des conclusions sur les méthodes de prospective les plus utiles pour les Services vétérinaires.


El mundo hace frente a un rosario de problemas ligados a la agricultura, y en especial al sector ganadero, entre ellos las amenazas que pesan sobre la productividad, el medio natural y la salud humana. Aunque se ha investigado mucho sobre los posibles riesgos y sus condicionantes, la pandemia de COVID-19 de 2020 puso de relieve cuán afectados pueden verse los gobiernos por choques hasta cierto punto predecibles, pero para los cuales suelen estar mal preparados. Las políticas tienen por objetivo anticipar el futuro y también influir en él. Los Servicios Veterinarios nacionales, como artífices que son de ciertas políticas, cumplen una importante función a la hora de prever y orientar el futuro de su país y del mundo. En la primera parte del artículo, la autora resume toda una serie de métodos y herramientas de prospectiva que emplean los Servicios Veterinarios o los investigadores en veterinaria o que revisten interés para ellos. A continuación presenta un ejemplo de adaptación y aplicación de un marco de prospectiva concebido específicamente para los Servicios Veterinarios. Por último, extrae conclusiones sobre los métodos de prospectiva que son de utilidad para los Servicios Veterinarios.


Assuntos
COVID-19 , Medicina Veterinária , Agricultura , Animais , COVID-19/veterinária , Humanos , Gado , Pandemias , SARS-CoV-2
18.
Rev Sci Tech ; 40(2): 469-481, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34542100

RESUMO

Animal welfare is an essential component of the future of sustainable agriculture and the United Nations Sustainable Development Goals. There is growing global recognition of the importance of animal welfare, which must always be considered as part of the decision-making around food and nutrition security. Veterinary Services, encompassing public and private veterinarians and para-veterinarians, are custodians of animal welfare and key players in future actions to improve it. The welfare of animals is everyone's responsibility, from the individual farmer and practitioner to policymakers at the national and intergovernmental level. In this paper, after providing background information about current animal welfare issues and identifying animal welfare risks, the authors make a number of recommendations for action at the institutional and individual level. They do so because while the former is essential to generate change at scale and effective resourcing, the latter can create immediate action at a local level and drive change from the ground up. Without coordinated action from Veterinary Services, opportunities to improve animal welfare, alongside human and environmental health and well-being, may very well be lost, and animal welfare may fail to improve or even be at risk of decline.


L'accélération de la perturbation numérique depuis quelques années est spectaculaire, transformant tous les secteurs de l'économie, y compris la production animale, la santé animale et le bien-être des animaux. Les auteurs s'intéressent à certaines technologies numériques de pointe qui pourraient influencer le devenir des Services vétérinaires. Toutes ces technologies sont orientées données et trouvent leur illustration dans trois exemples qui se répartissent dans les catégories suivantes : a) les technologies sans fil et mobiles appliquées au suivi de la santé animale, à la surveillance des maladies, aux notifications des foyers et à l'échange d'informations ; b) les technologies avancées de traitement des données, dont les mégadonnées et l'analytique de données qui servent à mettre en évidence des structures sous-jacentes, à extraire des schémas prédictifs, à relever des corrélations et à générer d'autres informations ; c) des technologies prometteuses comme les applications « blockchain ¼ (chaînes de blocs) utilisées pour une gestion efficace et efficiente de diverses chaînes d'approvisionnement en intrants. Les auteurs résument brièvement les défis actuels associés au recours accru à ces technologies dans le secteur de la santé animale et en font ressortir certaines répercussions sur les Services vétérinaires. Les technologies numériques vont profondément affecter les modalités de la prestation des services de santé animale ainsi que la gestion des systèmes de santé animale. Par conséquent, il est crucial que les Services vétérinaires anticipent cette évolution et s'adaptent à la transformation numérique en cours. L'investissement dans les nouvelles technologies et les efforts visant à doter les professionnels vétérinaires actuels et futurs des compétences et des connaissances numériques nécessaires pour rester informés et au centre de l'innovation numérique dans le domaine de la santé animale doivent être les priorités des prochaines années.


El bienestar animal es un componente esencial de la agricultura sostenible del futuro y de los Objetivos de Desarrollo Sostenible fijados por las Naciones Unidas. Su importancia está cada vez más clara en todo el mundo. El bienestar de los animales debe ser siempre tenido en cuenta en los procesos decisorios que tocan a la seguridad alimentaria y nutricional. Los Servicios Veterinarios, que comprenden tanto a los veterinarios públicos y privados como al personal paraveterinario, son custodios del bienestar animal y agentes clave de toda acción futura encaminada a mejorarlo. Para lograr que el bienestar animal mejore desde ahora mismo, allí donde haga falta, y asegurar que siga un rumbo de constante progreso en el futuro, es preciso que todos los interlocutores, desde los productores y cuidadores hasta los planificadores de políticas de ámbito nacional e intergubernamental, hagan suya esta responsabilidad. Tras presentar información básica sobre los actuales problemas de bienestar animal y señalar los riesgos existentes en la materia, los autores formulan una serie de recomendaciones para actuar tanto desde las instituciones como a título individual, sabedores de que el primer nivel es fundamental para inducir cambios a gran escala y movilizar recursos eficazmente, mientras que el segundo puede generar inmediatamente acciones a escala local e impulsar desde ahí cambios en sentido ascendente. A falta de una labor coordinada de los Servicios Veterinarios, es muy posible que se pierdan oportunidades para mejorar el bienestar animal, junto con la salud y el bienestar de personas y ecosistemas, y que los niveles de bienestar animal no mejoren o, incluso, corran peligro de deterioro.


Assuntos
Médicos Veterinários , Medicina Veterinária , Agricultura , Bem-Estar do Animal , Animais , Fazendeiros , Humanos
19.
Rev Sci Tech ; 40(2): 567-584, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34542092

RESUMO

Investments in animal health and Veterinary Services can have a measurable impact on the health of people and the environment. These investments require a baseline metric that describes the burden of animal health and welfare in order to justify and prioritise resource allocation and from which to measure the impact of interventions. This paper is part of a process of scientific enquiry in which problems are identified and solutions sought in an inclusive way. It poses the broad question: what should a system to measure the animal disease burden on society look like and what value would it add? Moreover, it aims to do this in such a way as to be accessible by a wide audience, who are encouraged to engage in this debate. Given that farmed animals, including those raised by poor smallholders, are an economic entity, this system should be based on economic principles. These poor farmers are negatively impacted by disparities in animal health technology, which can be addressed through a mixture of supply-led and demand-driven interventions, reinforcing the relevance of targeted financial support from government and non-governmental organisations. The Global Burden of Animal Diseases (GBADs) Programme will glean existing data to measure animal health losses within carefully characterised production systems. Consistent and transparent attribution of animal health losses will enable meaningful comparisons of the animal disease burden to be made between diseases, production systems and countries, and will show how it is apportioned by people's socio-economic status and gender. The GBADs Programme will produce a cloud-based knowledge engine and data portal, through which users will access burden metrics and associated visualisations, support for decisionmaking in the form of future animal health scenarios, and the outputs of wider economic modelling. The vision of GBADs, strengthening the food system for the benefit of society and the environment, is an example of One Health thinking in action.


Les investissements réalisés en santé animale et dans les Services vétérinaires ont un impact mesurable sur la santé des personnes et de l'environnement. Le système de mesure appliqué à ces investissements doit reposer sur un référentiel de base décrivant l'impact de la santé et du bien-être animal de manière à justifier et classer par priorités les ressources allouées et à mesurer les effets des interventions. Les auteurs présentent une étude conduite dans le cadre d'une enquête scientifique destinée à identifier les problèmes et à rechercher des solutions de manière inclusive. L'étude pose la question de savoir à quoi devrait ressembler un système conçu pour mesurer l'impact sur la société des maladies animales, et quelle serait sa valeur ajoutée. En outre, l'étude est conduite de manière à être accessible à une large audience afin d'encourager cette dernière à participer aux discussions. Étant donné que les animaux d'élevage constituent une entité économique, y compris les animaux appartenant à des éleveurs pauvres, le système de mesure doit reposer sur des principes économiques. Les exploitants pratiquant une agriculture de subsistance subissent les effets négatifs des disparités entre les différentes technologies applicables à la santé animale, disparités auxquelles il est possible de remédier par le biais d'interventions associant des mesures dictées par l'offre et par la demande et en renforçant l'efficacité du soutien financier ciblé apporté par les organisations gouvernementales et non gouvernementales. Le Programme « L'impact mondial des maladies animales ¼ (GBADs) aura pour tâche de glaner les données existantes afin de mesurer les pertes associées à la santé animale au sein de systèmes de production qui auront été soigneusement caractérisés au préalable. Grâce à l'élucidation cohérente et transparente des pertes imputables à chaque problème de santé animale, des comparaisons pertinentes pourront être effectuées concernant l'impact des maladies animales par maladies, par systèmes de production et par pays, et la répartition de cet impact dans les populations concernées suivant le statut socio-économique et le genre des intéressés sera mieux comprise. Le Programme GBADs entend créer un moteur de recherche et un portail de données qui seront disponibles sur le Cloud et donneront aux utilisateurs l'accès à des outils de mesure de l'impact des maladies et à d'autres informations présentées sous forme graphique, ainsi qu'à des outils d'aide à la décision sous forme de scénarios prospectifs sur la santé animale et aux résultats d'études plus larges de modélisation économique. La vision du GBADs, renforcer le système de production de denrées alimentaires au profit de la société et de l'environnement, est un exemple de mise en oeuvre du concept Une seule santé.


Las inversiones en sanidad animal y en los Servicios Veterinarios pueden tener un efecto mensurable en la salud de las personas y el medio ambiente. Para efectuar estas inversiones se precisan parámetros que describan y cuantifiquen la situación de partida y el impacto de los problemas de sanidad y bienestar animales, a fin de poder, a partir de ahí, justificar y jerarquizar la asignación de recursos y medir los efectos de las intervenciones. Este artículo, inscrito en un proceso de indagación científica encaminado a detectar problemas y buscar soluciones de forma incluyente, plantea la cuestión general de cómo debería ser y qué valor añadido aportaría un sistema destinado a medir el impacto que imponen a la sociedad las enfermedades animales. Los autores, además, tratan de exponer la cuestión de manera que sea accesible a un público amplio, al que se alienta a participar en este debate. Dado que los animales de granja (incluidos los de pequeñas explotaciones) constituyen una entidad económica, tal sistema debería estar basado en principios económicos. Los productores que trabajan en régimen de subsistencia se ven negativamente afectados por las disparidades existentes en materia de tecnología zoosanitaria, disparidad que cabe corregir con una combinación de intervenciones marcadas por la oferta y otras marcadas por la demanda, dirigiendo así más selectivamente el apoyo económico de entidades gubernamentales y organizaciones no gubernamentales. El programa GBADs (El impacto global de las enfermedades animales) servirá para compilar datos ya existentes con el fin de medir las pérdidas zoosanitarias dentro de sistemas productivos cuidadosamente caracterizados. La atribución coherente y transparente de estas pérdidas zoosanitarias permitirá efectuar comparaciones significativas del impacto que representan las enfermedades animales en el caso de diferentes dolencias, sistemas productivos o países y pondrá de relieve cómo se distribuye este impacto en función del género y la condición socioeconómica de las personas. Por medio del programa GBADs se creará un motor de conocimiento y portal de datos ubicado en la nube que permita al usuario acceder a mediciones del impacto de enfermedades y representaciones gráficas conexas, a herramientas de apoyo a la adopción de decisiones, en forma de hipotéticas situaciones zoosanitarias futuras, y a los resultados de modelizaciones económicas más generales. La aspiración del programa GBADs ­ reforzar el sistema alimentario en beneficio de la sociedad y el medio ambiente ­ constituye un ejemplo de aplicación en la práctica del pensamiento en clave de Una sola salud.


Assuntos
Doenças dos Animais , Saúde Única , Doenças dos Animais/epidemiologia , Animais , Aquicultura , Gado
20.
Int J Aging Hum Dev ; 93(1): 562-583, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32394718

RESUMO

The purpose of this study was a cross-cultural examination of centenarians' personality through a person-centered approach to examine if there is a "resilient" personality profile consistent across cultures. Proxy reports information was obtained from family and close friends of 239 U.S. centenarians from the Georgia Centenarians Study and 272 Japanese centenarians from the Tokyo Centenarian Study. Latent profile analyses were conducted to identify personality profiles in centenarians from the United States and Japan. Two personality profiles were identified in both samples: a "resilient" personality profile and "nonresilient" personality profile. The "resilient" group had higher levels of positive personality traits with higher scores on agreeableness and extraversion and lower scores on neuroticism, conscientiousness, and openness. The "nonresilient" group had higher scores on neuroticism and lower scores on extraversion, openness, agreeableness, and conscientiousness. Fifty percent of U.S. centenarians and 65% of Japanese centenarians were in the "resilient" group.


Assuntos
Idoso de 80 Anos ou mais/psicologia , Comparação Transcultural , Personalidade , Idoso de 80 Anos ou mais/estatística & dados numéricos , Extroversão Psicológica , Feminino , Humanos , Japão , Masculino , Neuroticismo , Otimismo , Resiliência Psicológica , Estados Unidos
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