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1.
AIDS Behav ; 28(9): 3170-3183, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39014029

RESUMO

We examined past-year intimate partner violence (IPV), including psychological violence without physical/sexual violence, and health outcomes among people with HIV (PWH) in care in a multi-site U.S. cohort. Between 2016 and 2022, PWH reported 12-month psychological, physical, and sexual IPV in a routine assessment. We used linear and logistic regression models adjusted for age, race/ethnicity, and site to examine relationships with health outcomes. Among 9748 PWH (median age 50 years, 81% cisgender male/16% cisgender female/1% transgender female; 44% non-Hispanic white/36% non-Hispanic Black/15% Hispanic), 9.3% (n = 905) reported any IPV in the past 12 months; half reported psychological IPV without physical/sexual IPV (n = 453). PWH reporting any type of IPV were on average younger than those who did not experience IPV. In adjusted models, any IPV was associated with increased likelihood of unstable housing, HIV viral load detection (HIV viral load ≥ 75 copies/mL), moderate-to-severe depressive symptoms, anxiety with panic symptoms, substance use (methamphetamines, cocaine/crack, illicit opioids, marijuana, heavy episodic/hazardous drinking), and concern about exposure to sexually transmitted infection. PWH reporting any IPV in the past 12 months had 4.2% lower adherence to antiretroviral therapy, 2.4 more HIV-related symptoms, a 1.9 point higher HIV stigma score, and a 9.5% lower quality of life score than those without IPV. We found similar associations among PWH reporting only psychological IPV, without physical/sexual IPV. IPV was common among PWH. Half reporting IPV reported only psychological IPV and had similarly poor outcomes as those reporting physical/sexual IPV, demonstrating the need to assess psychological as well as physical and sexual IPV.


RESUMEN: Examinamos la violencia de la pareja íntima (intimate partner violence, IPV) del año anterior, incluida la violencia psicológica sin violencia física y sexual, así como los resultados sanitarios entre las personas con VIH (people with HIV, PWH) que reciben atención en una cohorte multicéntrica de los Estados Unidos. Entre 2016 y 2022, las PWH informaron situaciones de IPV psicológica, física y sexual durante los 12 meses en una evaluación de rutina. Se utilizaron modelos de regresión lineal y logística ajustados por edad, raza/etnia y centro para examinar las relaciones con los resultados sanitarios. Entre 9748 PWH (mediana de edad de 50 años, 81% de hombres cisgénero/16% de mujeres cisgénero/1% de mujeres transgénero; 44% de blancos no hispanos/36% de negros no hispanos/15% de hispanos), el 9,3% (n = 905) informaron haber sufrido algún tipo de IPV en los últimos 12 meses; la mitad informó situaciones de IPV psicológica sin IPV física y sexual (n = 453). Las PWH que informaron de cualquier tipo de IPV fueron, en promedio, más jóvenes que las que no sufrieron IPV. En los modelos ajustados, cualquier IPV se asoció con una mayor probabilidad de vivienda inestable, detección de carga viral del VIH (carga viral del VIH ≥ 75 copias/ml), síntomas depresivos de moderados a graves, ansiedad con síntomas de pánico, consumo de sustancias (metanfetaminas, cocaína/crack, opioides ilícitos, marihuana, consumo excesivo episódico/peligroso de alcohol) y preocupación por la exposición a infecciones de transmisión sexual. Las PWH que informaron alguna situación de IPV en los últimos 12 meses tuvieron un 4,2% menos de cumplimiento de la terapia antirretrovírica, un 2,4% más de síntomas relacionados con el VIH, una puntuación de estigma del VIH 1,9 puntos más alta y una puntuación de calidad de vida un 9,5% más baja que las que no sufrieron IPV. Se encontraron asociaciones similares entre las PWH que informaron solo IPV psicológica, sin IPV física y sexual. La IPV fue común entre las PWH. La mitad de las personas que informaron IPV solo informaron IPV psicológica y tuvieron resultados igualmente deficientes que los que informaron IPV física y sexual, lo que demuestra la necesidad de evaluar la IPV psicológica, al igual que la IPV física y sexual.


Assuntos
Infecções por HIV , Violência por Parceiro Íntimo , Humanos , Feminino , Masculino , Violência por Parceiro Íntimo/psicologia , Violência por Parceiro Íntimo/estatística & dados numéricos , Infecções por HIV/psicologia , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto , Parceiros Sexuais/psicologia , Fatores de Risco , Estudos de Coortes , Carga Viral , Depressão/epidemiologia , Depressão/psicologia
2.
Neuroimage ; 297: 120716, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38955254

RESUMO

MAO-A catalyzes the oxidative degradation of monoamines and is thus implicated in sex-specific neuroplastic processes that influence gray matter (GM) density (GMD) and microstructure (GMM). Given the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy (GHT) represent a valuable cohort to potentially investigate sex steroid-induced changes of GM and concomitant MAO-A density. Here, we investigated the effects of GHT over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men underwent two MRI scans in a longitudinal design. PET scans using [11C]harmine were performed before each MRI session in a subset of 35 individuals. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: pFWE+Bonferroni < 0.025). In terms of MAO-A distribution volume, no significant effects were found. Additionally, the sexual desire inventory (SDI) was applied to assess GHT-induced changes in sexual desire, showing an increase of SDI scores among transgender men. Changes in the GMD of the bilateral insula showed a moderate correlation to SDI scores (rho = - 0.62, pBonferroni = 0.047). The present results are indicative of a reliable influence of gender-affirming hormone therapy on 1) GMD and GMM following an interregional pattern and 2) sexual desire specifically among transgender men.


Assuntos
Substância Cinzenta , Monoaminoxidase , Tomografia por Emissão de Pósitrons , Pessoas Transgênero , Humanos , Substância Cinzenta/efeitos dos fármacos , Substância Cinzenta/diagnóstico por imagem , Masculino , Adulto , Feminino , Monoaminoxidase/sangue , Monoaminoxidase/metabolismo , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Longitudinais
3.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38870326

RESUMO

CASE: We present a 64-year-old woman with loss of lumbar lordosis with a preoperative computed tomography scan demonstrating the presence of an intrapelvic kidney with aberrant vasculature. A 2-level anterior lumbar interbody fusion with a 2-level oblique interbody fusion was planned. An anterior approach was successfully used to access the anterior spine without damaging the pelvic kidney. CONCLUSION: Anatomic variations, both congenital and acquired, can pose significant challenges to surgeons during their dissection. We present a case where multilevel anterior interbody cage placement can be safely performed, even in a patient whose anatomy is complicated by an intrapelvic kidney.


Assuntos
Vértebras Lombares , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Feminino , Pessoa de Meia-Idade , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Rim/diagnóstico por imagem , Rim/anormalidades , Rim/cirurgia , Tomografia Computadorizada por Raios X
4.
Free Radic Biol Med ; 215: 106-111, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38401827

RESUMO

The recent publication by Azzi and colleagues puts forth the argument that only RRR-α-tocopherol should be considered as vitamin E from a physiological point of view. They base their argument primarily on the assertion that only this form has been used to treat stark vitamin E deficiency in humans (known as AVED, or Ataxia with Vitamin E Deficiency). Azzi et al. also argue that other chemically similar molecules, such as tocopherols other than α-tocopherol and tocotrienols do not provide vitamin E activity. Azzi and colleagues are correct on this second point. An investigation into the biological activities of vitamin E, and the mechanisms behind these activities, confirms that physiological vitamin E activity is limited to certain α-tocopherol forms. However, it is also clear that these activities are not restricted only to the RRR-form but include other 2R-forms as well. Indeed, the α-tocopherol transfer protein (α-TTP), which is critical to mediate vitamin E trafficking and biological activity, and genetic defects of which lead to vitamin E deficiency, binds well to all 2R-forms of α-tocopherol. Furthermore, both RRR-α-tocopherol and the other 2R-forms are maintained in human plasma and distributed to tissues and organs, whereas the 2S-stereoisomers are excreted quickly. As such, in recent years the definition of vitamin E including both 2R- and RRR-α-tocopherol has gained both broad scientific and regulatory acceptance. Consistent with this understanding, we provide evidence that AVED has indeed been treated successfully with forms in addition to RRR-α-tocopherol, again arguing against the restriction of the definition to RRR-α-tocopherol only. Finally, we provide evidence against any safety concerns utilizing the currently accepted definition of vitamin E.


Assuntos
Deficiência de Vitamina E , Vitamina E , Humanos , Vitamina E/farmacologia , Vitamina E/metabolismo , alfa-Tocoferol/farmacologia , Estereoisomerismo , Antioxidantes/farmacologia , Antioxidantes/química , Deficiência de Vitamina E/tratamento farmacológico
5.
AIDS Care ; 36(5): 618-630, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37419138

RESUMO

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.


Assuntos
Infecções por HIV , Drogas Ilícitas , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias , Adulto , Masculino , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Transtornos Relacionados ao Uso de Substâncias/complicações , Antirretrovirais/uso terapêutico , Etanol/uso terapêutico , Metanfetamina/uso terapêutico , Adesão à Medicação
6.
AIDS Care ; 35(11): 1741-1748, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36912767

RESUMO

Evidence suggests adverse health effects from vaporized nicotine (VN) use, such as electronic "e" cigarettes, and limited efficacy to aid tobacco cessation. People with HIV (PWH) smoke tobacco at higher rates than the general population, with greater morbidity, highlighting the necessity of effective tobacco cessation tools. PWH may be more vulnerable to adverse effects of VN. Using semi-structured 1:1 interviews, we examined health beliefs regarding VN, patterns of use, and perceived effectiveness for tobacco cessation among PWH in HIV care at three geographically diverse U.S. sites. PWH (n = 24) had limited understanding of VN product content or health effects, presuming VN less harmful than tobacco cigarettes (TC). VN failed to adequately replicate the psychoactive effects or desired ritual of smoking TC. Concurrent TC use, and continuous VN use throughout the day, was common. Satiety using VN was elusive, and consumption quantity was difficult to track. VN had limited desirability and durability as a TC cessation tool among the interviewed PWH.


Assuntos
Infecções por HIV , Abandono do Hábito de Fumar , Humanos , Nicotina , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/etiologia , Nível de Saúde , Fumar/efeitos adversos , Fumar/epidemiologia
7.
J Clin Microbiol ; 61(1): e0155822, 2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36602344

RESUMO

Cystic fibrosis (CF) is characterized by mutations of CFTR that lead to increased viscous secretions, bacterial colonization, and recurrent infections. Chronic Pseudomonas aeruginosa infection in persons with CF is associated with progressive and accelerated lung function decline despite aggressive antibiotic treatment. We report the management of respiratory infections in persons with CF with antibiotic therapy that was based on the recommendations of AtbFinder, a novel, rapid, culture-based diagnostic test system that employs a novel paradigm of antibiotic selection. AtbFinder mimics bacterial interactions with antibiotics at concentrations that can be achieved in affected tissues or organs and models conditions of interbacterial interactions within polymicrobial biofilms. This open-label, single-arm, investigator-initiated clinical study was designed to identify the efficacy of antibiotics selected using AtbFinder in persons with CF. Microbiological and clinical parameters were assessed following the change of antibiotic therapy to antibiotics selected with AtbFinder between January 2016 and December 2018 and retrospectively compared with clinical data collected between January 2013 and December 2015. We enrolled 35 persons with CF (33 with chronic P. aeruginosa colonization). Antibiotics selected using AtbFinder resulted in clearance of P. aeruginosa in 81.8% of subsequent cultures, decreased pulmonary exacerbations from 1.21 per patient per annum to 0, and an increase in predicted percent predicted forced expiratory volume in 1 s up to 28.4% from baseline. The number of systemic antibiotic courses used in patients after switching to the AtbFinder-selected therapy was reduced from 355 to 178. These findings describe the superiority of antibiotic regimens selected with AtbFinder compared with routine antimicrobial susceptibility testing.


Assuntos
Fibrose Cística , Infecções por Pseudomonas , Humanos , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Fibrose Cística/microbiologia , Estudos Retrospectivos , Testes de Sensibilidade Microbiana , Antibacterianos/uso terapêutico , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Testes Diagnósticos de Rotina
8.
Microbiol Resour Announc ; 11(10): e0049922, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36190248

RESUMO

We report the draft genome sequence of a putative new genus and species, Siliceabacter maunaloa, in the family Solirubrobacteraceae. The members of this family of Actinobacteria are generally Gram positive and mesophilic. Found within a Hawaiian lava tube, this microbe illuminates the types of prokaryotes inhabiting secondary minerals in subsurface basaltic environments.

9.
Microbiol Resour Announc ; 11(11): e0055622, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36264256

RESUMO

Here, we present the draft genome for a new putative species, Gaiellasilicea maunaloa, most closely related to Gaiella occulta, within the phylum Actinobacteria. This group contains Gram-negative, aerobic mesophilic species. This metagenome-assembled genome (MAG) contributes to knowledge of life in volcanic environments and may inform investigations of life beyond Earth.

10.
J Nutr Health Aging ; 25(7): 869-877, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34409964

RESUMO

OBJECTIVES: The intima-media thickness of the common carotid artery (ccIMT) is an established risk marker for cardiovascular disease (CVD). However, it is unclear whether lifestyle interventions can easily demonstrate an improvement in ccIMT. The objective was to test if our intervention would beneficially affect ccIMT (among other CVD markers). DESIGN: Non-randomized controlled trial. SETTING: Rural northwest Germany. PARTICIPANTS: Middle-aged and elderly participants from the general population (intervention: n = 114; control: n = 87). INTERVENTION: A community-based, 6-month controlled lifestyle intervention focusing on four areas of lifestyle change: a plant-based diet, physical activity, stress management, and an improved social life. A strong emphasis was on dietary change. MEASUREMENTS: We tested whether ccIMT change from baseline to 6 months was different between groups. RESULTS: With all participants included, no significant difference in mean ccIMT change between groups was observed (p = 0.708). However, in a subgroup analysis with participants with high baseline mean ccIMT (≥0.800 mm) a significant difference in mean ccIMT change between intervention (-0.023 [95% CI -0.052, 0.007] mm; n = 22; baseline mean ccIMT: 0.884 ± 0.015 mm) and control (0.041 [95% CI 0.009, 0.073] mm; n = 13; baseline mean ccIMT: 0.881 ± 0.022 mm) was observed (p = 0.004). Adjusting for potential confounders did not substantially alter the results. CONCLUSION: The results indicate that healthy lifestyle changes can beneficially affect ccIMT within 6 months and that such a beneficial effect may be more easily demonstrated if participants with high baseline ccIMT are recruited. The observed effect is of relevance for the prevention of CVD events, including myocardial infarction and stroke.


Assuntos
Doenças Cardiovasculares , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estilo de Vida Saudável , Idoso , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ultrassonografia
11.
Osteoarthritis Cartilage ; 29(11): 1549-1563, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34461226

RESUMO

OBJECTIVE: To explore how systemic factors that modify knee osteoarthritis risk are connected to 'whole-joint' structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics. METHODS: Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9-13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group. RESULTS: High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1ß and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites. CONCLUSION: Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.


Assuntos
Dieta Hiperlipídica , Condicionamento Físico Animal , Joelho de Quadrúpedes/diagnóstico por imagem , Joelho de Quadrúpedes/patologia , Líquido Sinovial/metabolismo , Animais , Biomarcadores/sangue , Quimiocina CCL2/sangue , Condrócitos/patologia , Intolerância à Glucose , Hipertrofia , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-8/sangue , Leptina/sangue , Metabolômica , Camundongos Endogâmicos C57BL , Osteoartrite , Microtomografia por Raio-X
12.
Neuroimage ; 236: 118039, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33852940

RESUMO

Animal studies using selective serotonin reuptake inhibitors (SSRIs) and learning paradigms have demonstrated that serotonin is important for flexibility in executive functions and learning. SSRIs might facilitate relearning through neuroplastic processes and thus exert their clinical effects in psychiatric diseases where cognitive functioning is affected. However, translation of these mechanisms to humans is missing. In this randomized placebo-controlled trial, we assessed functional brain activation during learning and memory retrieval in healthy volunteers performing associative learning tasks aiming to translate facilitated relearning by SSRIs. To this extent, seventy-six participants underwent three MRI scanning sessions: (1) at baseline, (2) after three weeks of daily associative learning and subsequent retrieval (face-matching or Chinese character-noun matching) and (3) after three weeks of relearning under escitalopram (10 mg/day) or placebo. Associative learning and retrieval tasks were performed during each functional MRI (fMRI) session. Statistical modeling was done using a repeated-measures ANOVA, to test for content-by-treatment-by-time interaction effects. During the learning task, a significant substance-by-time interaction was found in the right insula showing a greater deactivation in the SSRI cohort after 21 days of relearning compared to the learning phase. In the retrieval task, there was a significant content-by-time interaction in the left angular gyrus (AG) with an increased activation in face-matching compared to Chinese-character matching for both learning and relearning phases. A further substance-by-time interaction was found in task performance after 21 days of relearning, indicating a greater decrease of performance in the placebo group. Our findings that escitalopram modulate insula activation demonstrates successful translation of relearning as a mechanism of SSRIs in human. Furthermore, we show that the left AG is an active component of correct memory retrieval, which coincides with previous literature. We extend the function of this region by demonstrating its activation is not only stimulus dependent but also time constrained. Finally, we were able to show that escitalopram aids in relearning, irrespective of content.


Assuntos
Aprendizagem por Associação/efeitos dos fármacos , Córtex Cerebral , Citalopram/farmacologia , Rememoração Mental/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Citalopram/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Adulto Jovem
13.
Int J Neuropsychopharmacol ; 24(7): 542-550, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-33667309

RESUMO

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are predominantly prescribed for people suffering from major depressive disorder. These antidepressants exert their effects by blocking the serotonin transporter (SERT), leading to increased levels of serotonin in the synaptic cleft and subsequently to an attenuation of depressive symptoms and elevation in mood. Although long-term studies investigating white matter (WM) alterations after exposure to antidepressant treatment exist, results on the acute effects on the brain's WM microstructure are lacking. METHODS: In this interventional longitudinal study, 81 participants were included (33 patients and 48 healthy controls). All participants underwent diffusion weighted imaging on 2 separate days, receiving either citalopram or placebo using a randomized, double-blind, cross-over design. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated within the FMRIB software library and analyzed using tract-based spatial statistics. RESULTS: The repeated-measures ANOVA model revealed significant decreases after SSRI administration in mean diffusivity, axial diffusivity, and radial diffusivity regardless of the group (P < .05, family-wise error [FWE] corrected). Results were predominantly evident in frontal WM regions comprising the anterior corona radiata, corpus callosum, and external capsule and in distinct areas of the frontal blade. No increases in diffusivity were found, and no changes in fractional anisotropy were present. CONCLUSIONS: Our investigation provides the first evidence, to our knowledge, that fast WM microstructure adaptations within 1 hour after i.v. SSRI administration precede elevations in mood due to SSRI treatment. These results add a new facet to the complex mode of action of antidepressant therapy. This study was registered at clinicaltrials.gov with the identifier NCT02711215.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Substância Branca/efeitos dos fármacos , Adulto , Transtorno Depressivo Maior/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Estudos Longitudinais , Masculino , Substância Branca/diagnóstico por imagem , Adulto Jovem
14.
Osteoarthritis Cartilage ; 29(6): 882-893, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33744432

RESUMO

OBJECTIVE: To compare the early responses to joint injury in conventional and germ-free mice. DESIGN: Post-traumatic osteoarthritis (PTOA) was induced using a non-invasive anterior cruciate ligament rupture model in 20-week old germ-free (GF) and conventional C57BL/6 mice. Injury was induced in the left knees of n = 8 GF and n = 10 conventional mice. To examine the effects of injury, n = 5 GF and n = 9 conventional naïve control mice were used. Mice were euthanized 7 days post-injury, followed by synovial fluid recovery for global metabolomic profiling and analysis of epiphyseal trabecular bone by micro-computed tomography (µCT). Global metabolomic profiling assessed metabolic differences in the joint response to injury between GF and conventional mice. Magnitude of trabecular bone volume loss measured using µCT assessed early OA progression in GF and conventional mice. RESULTS: µCT found that GF mice had significantly less trabecular bone loss compared to conventional mice, indicating that the GF status was protective against early OA changes in bone structure. Global metabolomic profiling showed that conventional mice had greater variability in their metabolic response to injury, and a more distinct joint metabolome compared to their corresponding controls. Furthermore, differences in the response to injury in GF compared to conventional mice were linked to mouse metabolic pathways that regulate inflammation associated with the innate immune system. CONCLUSIONS: These results suggest that the gut microbiota promote the development of PTOA during the acute phase following joint trauma possibly through the regulation of the innate immune system.


Assuntos
Osso Esponjoso , Epífises/metabolismo , Epífises/microbiologia , Microbioma Gastrointestinal , Metabolômica , Osteoartrite/metabolismo , Osteoartrite/microbiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
16.
Eur J Neurol ; 28(2): 579-586, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33065762

RESUMO

BACKGROUND AND PURPOSE: Infections with human herpesvirus 6A (HHV-6A) and Epstein-Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV-6A associated risks of developing MS. METHODS: In this nested case-control study, Swedish biobanks were accessed to find pre-symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead-based multiplex assay was used to determine serological response against EBV and HHV-6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. RESULTS: Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20-29 and 30-39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV-6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6-2.7). CONCLUSIONS: This study suggests EBV infection after adolescence and age independent HHV-6A infection as risk factors for MS.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 6 , Esclerose Múltipla , Adolescente , Estudos de Casos e Controles , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4 , Humanos , Esclerose Múltipla/epidemiologia , Fatores de Risco
17.
Rev Chilena Infectol ; 37(1): 32-36, 2020 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-32730397

RESUMO

BACKGROUND: Sex workers, people with drug addiction, early onset of sexual activity population, and criminal population, are considered the groups most at risk of contracting sexually transmitted infections (STIs). AIM: To determine the prevalence of infection by Neisseria gonorrhoeae in inmates of the Preventive Detention Center (CDP) at Arica and Parinacota Region, Chile. The Scientific Ethical Committee of Universidad de Tarapacá approved this study. METHOD: 140 inmates participated, who voluntarily agreed to be part of the study and signed an informed consent. A sample of urethral meatus was taken to investigate N. gonorrhoeae, and an epidemiological survey was applied, which included age, drug use, overcrowding, among others. RESULTS: The prevalence of the agent was 16.4% in inmates of the Arica CDP, a result lower than that reported in other similar studies. CONCLUSION: Knowing the reality of the prevalence of this STI and some risk factors associated with the situation of deprivation of freedom in a tri-border area of northern Chile, contributes to the proposals for prevention programs in this vulnerable and at-risk population.


Assuntos
Gonorreia , Prisioneiros , Infecções Sexualmente Transmissíveis , Chile/epidemiologia , Gonorreia/epidemiologia , Gonorreia/prevenção & controle , Humanos , Neisseria gonorrhoeae/isolamento & purificação , Prevalência , Prisioneiros/estatística & dados numéricos , Fatores de Risco , Profissionais do Sexo/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle
18.
Transl Psychiatry ; 10(1): 104, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32265436

RESUMO

Serotonin neurotransmission may impact the etiology and pathology of attention-deficit and hyperactivity disorder (ADHD), partly mediated through single nucleotide polymorphisms (SNPs). We propose a multivariate, genetic and positron emission tomography (PET) imaging classification model for ADHD and healthy controls (HC). Sixteen patients with ADHD and 22 HC were scanned by PET to measure serotonin transporter (SERT') binding potential with [11C]DASB. All subjects were genotyped for thirty SNPs within the HTR1A, HTR1B, HTR2A and TPH2 genes. Cortical and subcortical regions of interest (ROI) were defined and random forest (RF) machine learning was used for feature selection and classification in a five-fold cross-validation model with ten repeats. Variable selection highlighted the ROI posterior cingulate gyrus, cuneus, precuneus, pre-, para- and postcentral gyri as well as the SNPs HTR2A rs1328684 and rs6311 and HTR1B rs130058 as most discriminative between ADHD and HC status. The mean accuracy for the validation sets across repeats was 0.82 (±0.09) with balanced sensitivity and specificity of 0.75 and 0.86, respectively. With a prediction accuracy above 0.8, the findings underlying the proposed model advocate the relevance of the SERT as well as the HTR1B and HTR2A genes in ADHD and hint towards disease-specific effects. Regarding the high rates of comorbidities and difficult differential diagnosis especially for ADHD, a reliable computer-aided diagnostic tool for disorders anchored in the serotonergic system will support clinical decisions.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/genética , Humanos , Aprendizado de Máquina , Polimorfismo de Nucleotídeo Único , Tomografia por Emissão de Pósitrons , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Triptofano Hidroxilase
19.
J Racial Ethn Health Disparities ; 7(5): 949-957, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32124421

RESUMO

OBJECTIVES: Non-Hispanic Blacks (NHB) and Hispanic/Latinos (H/L) are affected disproportionately by type 2 diabetes (T2DM) and its complications due to a myriad of reasons. Lack of diabetes education has been identified as one risk factor for poorly controlled diabetes. For persons using insulin, poor insulin administration technique can be problematic. Previous studies done demonstrating this have not been inclusive of NHB and H/L populations. As a result, this study aimed to use semi-structured interviews to examine insulin pen technique and training experience in NHB and H/L inpatients with T2DM. DESIGN: Semi-structured interviews comprised open- and close-ended questions, and prompts were conducted until reaching saturation in NHB and H/L inpatients with at least 3 months of insulin pen use. Data was analyzed by two researchers who completed a thematic analysis. RESULTS: Twenty semi-structured interviews were completed. Two major themes emerged from analysis included: patients prefer the insulin pen to syringes and vials and most had a lack of formal pen technique teaching. CONCLUSION: Although the insulin pen is a preferred modality of insulin delivery, this sampling of disparity patients demonstrates that insulin pen technique should be continually reassessed by health care providers as majority of the patients never had formal insulin pen teaching. Among those who did have training, they still made errors such as not priming the pen or shortened dwell time.


Assuntos
Atitude Frente a Saúde/etnologia , Negro ou Afro-Americano/psicologia , Diabetes Mellitus Tipo 2/etnologia , Hispânico ou Latino/psicologia , Insulina/administração & dosagem , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Injeções Subcutâneas/instrumentação , Injeções Subcutâneas/métodos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Adulto Jovem
20.
MAbs ; 12(1): 1725369, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32063088

RESUMO

Therapeutic proteins and emerging gene and cell-based therapies are attractive therapeutic tools for addressing unmet medical needs or when earlier conventional treatment approaches failed. However, the development of an immune response directed against therapeutic agents is a significant concern as it occurs in a substantial number of cases across products and indications. The specific anti-drug antibodies that develop can lead to safety adverse events as well as inhibition of drug activity or accelerated clearance, both phenomena resulting in loss of treatment efficacy. The European Immunogenicity Platform (EIP) is a meeting place for experts and newcomers to the immunogenicity field, designed to stimulate discussion amongst scientists across industry and academia, encourage interactions with regulatory agencies and share knowledge and the state-of-the-art of immunogenicity sciences with the broader scientific community. Here we report on the main topics covered during the EIP 10th Open Symposium on Immunogenicity of Biopharmaceuticals held in Lisbon, 26-27 February 2019, and the 1-d training course on practical and regulatory aspects of immunogenicity held ahead of the conference. These main topics included immunogenicity testing, clinical relevance of immunogenicity, immunogenicity prediction, regulatory aspects, tolerance induction as a mean to mitigate immunogenicity and immunogenicity in the context of gene therapy.


Assuntos
Anticorpos/imunologia , Produtos Biológicos/imunologia , Animais , Europa (Continente) , Humanos
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