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1.
Clin Infect Dis ; 78(1): 122-124, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-37740255

RESUMO

We report 12 patients with persistent viremia on oral antiretroviral therapy who were initiated on injectable cabotegravir/rilpivirine (iCAB/RPV) without oral lead-in. All patients achieved viral suppression without any virologic rebound. iCAB/RPV may be considered as an option for patients unable to maintain suppression on oral antiretroviral therapy.


Assuntos
Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Piridonas , Humanos , Rilpivirina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico
2.
J Sex Med ; 21(7): 596-604, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38808370

RESUMO

BACKGROUND: There are varying reports of immunohistochemically detected prostatic marker protein distribution in glands associated with the female urethra that may be related to tissue integrity at the time of fixation. AIM: In this study we used tissue derived from rapid autopsies of female patients to determine the distribution of glandular structures expressing prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) along the female urethra and in surrounding tissues, including the anterior vaginal wall (AVW). METHODS: Tissue blocks from 7 donors that contained the entire urethra and adjacent AVW were analyzed. These tissue samples were fixed within 4-12 hours of death and divided into 5-mm transverse slices that were paraffin embedded. Sections cut from each slice were immunolabeled for PSA or PSAP and a neighboring section was stained with hematoxylin and eosin. The sections were reviewed by light microscopy and analyzed using QuPath software. OBSERVATIONS: In tissue from all donors, glandular structures expressing PSA and/or PSAP were located within the wall of the urethra and were present along its whole length. RESULTS: In the proximal half of the urethra from all donors, small glands expressing PSAP, but not PSA, were observed adjacent to the and emptying into the lumen. In the distal half of the urethra from 5 of the 7 donors, tubuloacinar structures lined by a glandular epithelium expressed both PSA and PSAP. In addition, columnar cells at the surface of structures with a multilayered transitional epithelium in the distal half of the urethra from all donors expressed PSAP. No glands expressing PSA or PSAP were found in tissues surrounding the urethra, including the AVW. CLINICAL IMPLICATIONS: Greater understanding of the distribution of urethral glands expressing prostatic proteins in female patients is important because these glands are reported to contribute to the female sexual response and to urethral pathology, including urethral cysts, diverticula, and adenocarcinoma. STRENGTHS AND LIMITATIONS: Strengths of the present study include the use of rapid autopsy to minimize protein degradation and autolysis, and the preparation of large tissue sections to demonstrate precise anatomical relations within all the tissues surrounding the urethral lumen. Limitations include the sample size and that all donors had advanced malignancy and had undergone previous therapy which may have had unknown tissue effects. CONCLUSION: Proximal and distal glands expressing prostate-specific proteins were observed in tissue from all donors, and these glands were located only within the wall of the urethra.


Assuntos
Fosfatase Ácida , Autopsia , Antígeno Prostático Específico , Uretra , Vagina , Humanos , Feminino , Uretra/patologia , Vagina/patologia , Vagina/química , Antígeno Prostático Específico/análise , Fosfatase Ácida/análise , Fosfatase Ácida/metabolismo , Pessoa de Meia-Idade , Idoso , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Tirosina Fosfatases/análise , Adulto , Biomarcadores/metabolismo , Imuno-Histoquímica
3.
AIDS Behav ; 28(1): 264-273, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37436595

RESUMO

Adherence to antiretroviral therapy (ART) and engagement in HIV care is critical to decrease HIV transmissions and optimize outcomes in people with HIV (PWH). In 2016, the CDC reported that 63% of incident HIV diagnoses were transmitted by PWH who were aware of their status but not virally suppressed. Adult Special Care Clinic (ASCC) designed and implemented a quality improvement (QI) program to facilitate linkage and increase viral suppression rates in PWH. ASCC utilized identified barriers to create a Linkage to Care (LTC) program with multiple components, including a LTC coordinator, proactive outreach, and standardized protocols. Logistic regression was used to compare 395 PWH enrolled during the post-QI phase (01 January 2019-31 December 2021) to 337 PWH enrolled during the pre-QI phase (01 January 2016-31 December 2018). Newly diagnosed PWH enrolled during the post-QI phase had significantly higher odds of achieving viral suppression compared to those enrolled during the pre-QI phase (aOR 2.22, 95% CI 1.37-3.59, p = .001). There was no significant difference between previously diagnosed but unengaged PWH enrolled during pre- and post-QI phases, although absolute viral suppression increased from 66.1 to 71.5% in this group. Both increasing age and having private insurance increased the likelihood of achieving viral suppression. Results highlight the potential impact on linkage to care and viral suppression rates of a standardized LTC program, addressing barriers to care for PWH. Additional focus should be placed on previously diagnosed but unengaged PWH to determine what parts of the intervention may be modified to increase viral suppression rates.


Assuntos
Infecções por HIV , Adulto , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Melhoria de Qualidade , Carga Viral
4.
AIDS Behav ; 27(6): 1870-1878, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36371748

RESUMO

Pre-exposure prophylaxis (PrEP) is underutilized among Black men who have sex with men (BMSM) in the Southern United States. We assessed comfort receiving PrEP at various locations among 65 BMSM. Chi-square and t-tests explored associations between demographics, experienced homophobia and racism, and comfort receiving PrEP. BMSM with greater experienced homophobia were less comfortable at academically affiliated clinics [X2(2, N = 59) = 10.61, p = 0.01], CBOs [X2(3, N = 59) = 10.02, p = 0.02], and STI/HIV clinics [X2(3, N = 59) = 8.63, p = 0.04]. Those with greater experienced racism were more comfortable receiving PrEP by mail [X2(3, N = 61) = 9.40, p = 0.02]. Homophobia and racism influence preferences of BMSM for where and how they receive PREP care. Private modes of PrEP delivery and interventions targeting provider and organizational bias should be explored.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Racismo , Minorias Sexuais e de Gênero , Masculino , Humanos , Estados Unidos , Homossexualidade Masculina , Mississippi , Infecções por HIV/prevenção & controle , Homofobia
5.
J Allergy Clin Immunol ; 148(4): 941-952, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34450118

RESUMO

JAK inhibitors (JAKIs) are a new class of targeted therapy that have entered clinical practice for the treatment of immune-mediated rheumatic conditions. JAKIs can block the signaling activity of a variety of proinflammatory cytokines and therefore have the potential to mediate therapeutic benefits across a wide range of immune-mediated conditions. Several JAKIs are licensed, and many more are undergoing clinical trials. Here we provide a narrative review of the current and upcoming JAKIs for adult immune-mediated rheumatic and related conditions, with a specific focus on efficacy in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, psoriasis, and inflammatory bowel disease. The overall safety profile of JAKIs appears largely comparable to that of existing biologic cytokine-targeting agents, particularly, TNF inhibitors, apart from risk of herpes zoster, which is increased for JAKIs. Importantly however, unresolved safety concerns remain, particularly relating to increased venous thromboembolism.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Psoríase/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Animais , Humanos
6.
South Med J ; 114(3): 144-149, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33655307

RESUMO

OBJECTIVES: To describe the demographics, clinical characteristics, and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) in an academic medical center in the southern United States. METHODS: Retrospective, observational cohort study of all adult patients (18 years and older) consecutively admitted with laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 infection between March 13 and April 25, 2020 at the University of Mississippi Medical Center. All of the patients either survived to hospital discharge or died during hospitalization. Demographics, body mass index, comorbidities, clinical manifestations, and laboratory findings were collected. Patient outcomes (need for invasive mechanical ventilation and in-hospital death) were analyzed. RESULTS: One hundred patients were included, 53% of whom were women. Median age was 59 years (interquartile range 44-70) and 66% were younger than 65. Seventy-five percent identified themselves as Black, despite representing 58% of hospitalized patients at our institution in 2019. Common comorbid conditions included hypertension (68%), obesity (65%), and diabetes mellitus (31%). Frequent clinical manifestations included shortness of breath (76%), cough (75%), and fever (64%). Symptoms were present for a median of 7 days (interquartile range 4-7) on presentation. Twenty-four percent of patients required mechanical ventilation and, overall, 19% died (67% of those requiring mechanical ventilation). Eighty-four percent of those who died were Black. On multivariate analysis, ever smoking (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.6) and history of diabetes mellitus (OR 5.9, 95% CI 1.5-24.3) were associated with mortality, and those admitted from home were less likely to die (vs outside facility, OR 0.2, 95% CI 0.0-0.7). Neither age, sex, race, body mass index, insurance status, nor rural residence was independently associated with mortality. CONCLUSIONS: Our study adds evidence that Black patients appear to be overrepresented in those hospitalized with and those who die from COVID-19, likely a manifestation of adverse social determinants of health. These findings should help guide preventive interventions targeting groups at higher risk of acquiring and developing severe COVID-19 disease.


Assuntos
COVID-19/epidemiologia , Hospitalização , Centros Médicos Acadêmicos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Índice de Massa Corporal , COVID-19/diagnóstico , COVID-19/terapia , Feminino , Hispânico ou Latino/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Mississippi , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , População Branca/estatística & dados numéricos
7.
AIDS Res Ther ; 17(1): 60, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032617

RESUMO

BACKGROUND: Rapid antiretroviral therapy (ART), ideally initiated within twenty-four hours of diagnosis, may be crucial in efforts to increase virologic suppression and reduce HIV transmission. Recent studies, including demonstration projects in large metropolitan areas such as Atlanta, Georgia; New Orleans, Louisiana; San Francisco, California; and Washington D.C., have demonstrated that rapid ART initiation is a novel tool for expediting viral suppression in clinical settings. Here we present an evaluation of the impact of a rapid ART initiation program in a community-based clinic in Jackson, MS. METHODS: We conducted a retrospective chart review of patients who were diagnosed with HIV at Open Arms Healthcare Center or were linked to the clinic for HIV care by the Mississippi State Department of Health Disease Intervention Specialists from January 1, 2016 to December 31, 2018. Initial viral load, CD4+ T cell count, issuance of an electronic prescription (e-script), subsequent viral loads until suppressed and patient demographics were collected for each individual seen in clinic during the review period. Viral suppression was defined as a viral load less than 200 copies/mL. Rapid ART initiation was defined as receiving an e-script for antiretrovirals within seven days of diagnosis. RESULTS: Between January 1, 2016 and December 31, 2018, 70 individuals were diagnosed with HIV and presented to Open Arms Healthcare Center, of which 63 (90%) completed an initial HIV counseling visit. Twenty-seven percent of patients were provided with an e-script for ART within 7 days of diagnosis. The median time to linkage to care for this sample was 12 days and 5.5 days for rapid ART starters (p < 0.001). Median time from diagnosis to viral suppression was 55 days for rapid ART starters (p = 0.03), a 22 day decrease from standard time to viral suppression. CONCLUSION: Our results provide a similar level of evidence that rapid ART initiation is effective in decreasing time to viral suppression. Evidence from this evaluation supports the use of rapid ART initiation after an initial HIV diagnosis, including same-day treatment.


Assuntos
Infecções por HIV , Instituições de Assistência Ambulatorial , Antirretrovirais/uso terapêutico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Estudos Retrospectivos , Carga Viral
8.
Spinal Cord ; 58(1): 25-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31388122

RESUMO

STUDY DESIGN: Retrospective audit. OBJECTIVES: Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI). SETTING: Western Australian Hospitals managing SCI patients. METHODS: Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts. RESULTS: Across the cohort (n = 70) UTI rate was 1.1 starts/100 days; UTI by multi-resistant organisms 0.1/100 days. Having ≥1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values < 0.001). For patients with ≥1 UTIs (n = 43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1 SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n = 38/70), protocols were followed (85.7% ≤ 6 h apart, 96.1% < 8 h), but 26% of IC volumes exceeded 500 mL; occasional volumes > 800 mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009; and 3.9, 95%CI 2.6-5.9, p-value < 0.001 respectively). CONCLUSIONS: Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS. SPONSORSHIP: None.


Assuntos
Tempo de Internação/estatística & dados numéricos , Traumatismos da Medula Espinal/epidemiologia , Cateterismo Urinário/estatística & dados numéricos , Infecções Urinárias/epidemiologia , Adulto , Cateteres de Demora/estatística & dados numéricos , Humanos , Incidência , Pacientes Internados/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos da Medula Espinal/complicações , Fatores de Tempo , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/etiologia , Austrália Ocidental/epidemiologia
9.
Clin J Sport Med ; 30(1): 83-90, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855916

RESUMO

BACKGROUND: Actovegin is a biological drug with a controversial history of use in the treatment of sports injuries during the past 60 years. Particular concerns have been raised about its ergogenic potential to enhance performance, but some of these have been based on little more than anecdote. OBJECTIVES: In this article, we review the most recent scientific evidence to determine the clinical efficacy, safety profile, and legal status of Actovegin. METHODS: We considered all studies directly commenting on experience with Actovegin use as the primary intervention within the past 10 years. Outcomes included mechanisms of action, clinical efficacy in enhancing muscle repair, any report of safety issues, and any evidence for ergogenic effect. RESULTS: Our database search returned 212 articles, abstracts were screened, and after inclusion/exclusion criteria were applied, 25 articles were considered: Publications included 11 primary research articles (7 in vitro studies and 4 clinical trials), 8 review articles, 5 editorials, and a single case report. CONCLUSIONS: Current literature is still yet to define the active compound(s) of Actovegin, but suggests that it shows antioxidant and antiapoptotic properties, and may also upregulate macrophage responses central to muscle repair. Clinical efficacy was supported by one new original research article, and the use of Actovegin to treat muscle injuries remains safe and supported. Two articles argued the ergogenic effect of Actovegin, but in vitro findings did not to translate to the outcomes of a clinical trial. An adequate and meaningful scientific approach remains difficult in a field where there is immense pressure to deliver cutting-edge therapies.


Assuntos
Antioxidantes/uso terapêutico , Traumatismos em Atletas/tratamento farmacológico , Heme/análogos & derivados , Músculo Esquelético/lesões , Antioxidantes/efeitos adversos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Heme/efeitos adversos , Heme/farmacologia , Heme/uso terapêutico , Humanos , Macrófagos/efeitos dos fármacos , Substâncias para Melhoria do Desempenho/uso terapêutico
10.
Biol Lett ; 15(1): 20180659, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30958217

RESUMO

Forest community assembly is usually framed in terms of sporophyte dynamics; however, the recruitment and maintenance of fern populations, frequently influential in forest composition and structure, are initially determined by gametophytes. Sporophytes of three Cyathea tree fern species show habitat partitioning along gradients of phosphorus and light; we asked whether gametophyte niche differences parallel this pattern. To compare niche characteristics among taxa we compared growth rates to a size threshold (≥3 mm) of gametophytes under controlled conditions using a multi-factorial, multi-level (3 × 4) experiment, varying irradiance (5.4 ± 4.4; 59.1 ± 44.3; 107 ± 74.1 µmol m-2 s-1) and orthophosphate concentrations (5, 10, 20, 40 mg kg-1). Gametophytes of the pioneer species C. medullaris developed to the size threshold across a broad range of phosphate and irradiance treatments (more than 20% of gametophytes in ≥ 7 of the 12 treatments), peaking at 20 mg kg-1 P and 60 µmol m-2 s-1 irradiance. The growth rates of the forest understorey species C. dealbata and C. smithii also peaked at 60 µmol m-2 s-1 but varied across treatments, suggesting niche differentiation along irradiance and orthophosphate gradients. Our analysis suggests that gametophyte development is strategically aligned to the ecological habits of sporophytes and that forest community assembly is likely strongly influenced by the independent gametophyte life-stage.


Assuntos
Gleiquênias , Células Germinativas Vegetais , Ecossistema , Florestas , Árvores
11.
Arch Phys Med Rehabil ; 99(10): 2118-2121, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29859181

RESUMO

We examined spinal cord injury (SCI) catheterization practices in Australia to understand practice patterns and consistency with research evidence. A national facilitated discussion forum was held during the annual Australian and New Zealand Spinal Cord Society conference attended by 66 conference delegates. Initially, presentations were given on the latest laboratory research examining bladder changes following SCI; an overview of evidence-based recommendations indicating that intermittent catheterization is best practice; and results of a single-center practice audit that demonstrated substantial delay in transition between acute SCI and intermittent catheterization. The ensuing discussion covered current catheterization practices in both inpatient SCI units and the community and highlighted gaps between evidence and practice, with considerable variation in practice between centers and settings. Reported challenges to implementing best practice included social, economic, and resource factors. A disconnect between hospital and community practice was also identified as an important barrier to long-term uptake of intermittent catheterization following acute SCI. The discussion identified 3 proposed activities: (1) explore current practice and bladder health following SCI in greater depth across SCI units and in local communities through audits and standardized biochemical analysis; (2) determine the behavioral drivers of current practice; and (3) develop a knowledge translation strategy to better align practice with current clinical practice guidelines.


Assuntos
Prática Clínica Baseada em Evidências/tendências , Guias de Prática Clínica como Assunto , Traumatismos da Medula Espinal/complicações , Bexiga Urinaria Neurogênica/terapia , Cateterismo Urinário/métodos , Austrália , Congressos como Assunto , Previsões , Humanos , Nova Zelândia , Traumatismos da Medula Espinal/fisiopatologia , Bexiga Urinária/fisiopatologia
13.
World J Orthop ; 15(5): 404-417, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38835689

RESUMO

The prevalence of diabetes mellitus and its associated complications, particularly diabetic foot pathologies, poses significant healthcare challenges and economic burdens globally. This review synthesises current evidence on the surgical management of the diabetic foot, focusing on the interplay between neuropathy, ischemia, and infection that commonly culminates in ulcers, infections, and, in severe cases, amputations. The escalating incidence of diabetes mellitus underscores the urgency for effective management strategies, as diabetic foot complications are a leading cause of hospital admissions among diabetic patients, significantly impacting morbidity and mortality rates. This review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers, infections, and skeletal pathologies such as Charcot arthropathy, emphasising the critical role of early diagnosis, comprehensive management strategies, and interdisciplinary care in mitigating adverse outcomes. In addressing surgical interventions, this review evaluates conservative surgeries, amputations, and reconstructive procedures, highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot pathologies. The integration of advanced diagnostic tools, novel surgical techniques, and postoperative care, including offloading and infection control, are discussed in the context of optimising healing and preserving limb function.

14.
J Physiol ; 591(11): 2867-84, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23551946

RESUMO

Following reinnervation of denervated rat tail arteries, nerve-evoked contractions are at least as large as those evoked in normally innervated arteries despite a much lower nerve terminal density. Here nerve-evoked contractions have been investigated after transection of half the sympathetic innervation of normal tail arteries. After 1 week, the noradrenergic plexus 50-70 mm along the tail was about half as dense as control. Excitatory junction potentials recorded in smooth muscle cells of arterial segments isolated in vitro were half their normal amplitude. Surprisingly, nerve-evoked contractions of isometrically mounted segments were not reduced in amplitude, as was also the case after only 3 days. After 1 week, enhancement of nerve-evoked contractions by blocking either neuronal re-uptake of noradrenaline with desmethylimipramine or prejunctional α2-adrenoceptors with idazoxan was similar to control, suggesting that these mechanisms are matched to the number of innervating axons. The relative contribution of postjunctional α2-adrenoceptors to contractions evoked by long trains of stimuli was enhanced but that of α1-adrenoceptors was unchanged. Transiently, sensitivity to the α1-adrenoceptor agonist phenylephrine was slightly increased. After 7 weeks, amplitudes of nerve-evoked contractions remained similar to control, and sensitivity to phenylephrine had recovered but that to the α2-adrenoceptor agonist clonidine was slightly raised. The normal amplitude of nerve-evoked contractions after partial denervation is only partly explained by the greater contribution of α2-adrenoceptors. While the post-receptor mechanisms activated by nerve-released transmitter may be modified to amplify the contractions after partial denervation, our findings suggest that these mechanisms are normally saturated, at least in this artery.


Assuntos
Artérias/fisiologia , Miócitos de Músculo Liso/fisiologia , Sistema Nervoso Simpático/fisiologia , Vasoconstrição , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Artérias/citologia , Artérias/inervação , Clonidina/farmacologia , Desipramina/farmacologia , Idazoxano/farmacologia , Contração Isométrica , Denervação Muscular , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/metabolismo , Junção Neuromuscular/fisiologia , Norepinefrina/metabolismo , Fenilefrina/farmacologia , Ratos , Potenciais Sinápticos , Cauda/irrigação sanguínea , Cauda/inervação
15.
Am J Physiol Heart Circ Physiol ; 304(2): H215-28, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23161877

RESUMO

In humans neural control of arterial vessels supplying skin in the extremities is particularly vulnerable to the effects of diabetes. Here the streptozotocin (STZ) rat model of type 1 diabetes was used to compare effects on neurovascular function in plantar metatarsal arteries (PMAs), which supply blood to skin of hind paw digits, with those in mesenteric arteries (MAs). Twelve weeks after STZ (60 mg/kg ip), wire myography was used to assess vascular function. In PMAs, lumen dimensions were unchanged but both nerve-evoked contractions and sensitivity to α(1) (phenylephrine, methoxamine)- and α(2) (clonidine)-adrenoceptor agonists were reduced. The density of perivascular nerve fibers was also reduced by ~25%. These changes were not observed in PMAs from STZ-treated rats receiving either a low dose of insulin that did not greatly reduce blood glucose levels or a high dose of insulin that markedly reduced blood glucose levels. In MAs from STZ-treated rats, nerve-evoked increases in force did not differ from control but, because lumen dimensions were ~20% larger, nerve-evoked increases in effective transmural pressure were smaller. Increases in effective transmural pressure produced by phenylephrine or α,ß-methylene ATP in MAs from STZ-treated rats were not smaller than control, but the density of perivascular nerve fibers was reduced by ~10%. In MAs, the increase in vascular dimensions is primarily responsible for reducing effectiveness of nerve-evoked constrictions. By contrast, in PMAs decreases in both the density of perivascular nerve fibers and the reactivity of the vascular muscle appear to explain impairment of neurovascular transmission.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Artérias Mesentéricas/inervação , Pele/irrigação sanguínea , Sistema Nervoso Simpático/fisiopatologia , Vasoconstrição , Vasodilatação , Trifosfato de Adenosina/metabolismo , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Relação Dose-Resposta a Droga , Estimulação Elétrica , Membro Posterior , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Ossos do Metatarso , Miografia , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Estreptozocina , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
16.
South Med J ; 106(7): 422-6, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23820323

RESUMO

The natural history of hepatitis C virus infection differs between women and men. Women demonstrate a slow rate of disease progression until menopause. Older women are more likely to develop fibrosis and are less responsive than younger women to pegylated interferon and ribavirin. Women of childbearing age have higher rates of sustained virologic response, but current therapies are contraindicated during pregnancy. Vertical transmission of hepatitis C virus occurs, but data supporting recommendations for prevention of mother-to-infant transmission are limited.


Assuntos
Hepatite C Crônica/terapia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/terapia , Adulto , Fatores Etários , Antivirais/uso terapêutico , Protocolos Clínicos , Feminino , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores Sexuais
17.
J Hand Surg Asian Pac Vol ; 28(5): 548-554, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37905362

RESUMO

Background: There is no consensus for the appropriate surgical management of symptomatic chronic ulnar collateral ligament (UCL) injuries of the thumb. The aim of this study is to systematically review the treatment of chronic thumb metacarpophalangeal (MCP) joint UCL injuries to determine the optimal approach to treatment. Methods: A systematic review of PubMed, Medline, Embase and ePub Ahead of Print was performed in accordance with Preferred Reporting of Items in Systematic Review and Meta-Analysis (PRISMA) guidelines. Results: Data from 11 studies using various surgical techniques in 245 thumbs were heterogenous and meta-analysis of results not possible. These data were qualitatively assessed. Direct repair, reconstruction with free tendon grafts and arthrodesis all demonstrated favourable outcomes with patient-reported outcome measures (PROMs). Conclusions: Direct repair can be safely performed more than 2 months following injury. Arthrodesis may be considered in heavy manual labourers or those with osteoarthrosis. Tendon grafting is safe, yet the optimal type and configuration are yet to be determined for reconstructive methods. Level of Evidence: Level III (Therapeutic).


Assuntos
Ligamento Colateral Ulnar , Ligamentos Colaterais , Traumatismos da Mão , Humanos , Ligamento Colateral Ulnar/lesões , Ligamentos Colaterais/lesões , Traumatismos da Mão/cirurgia , Tendões , Polegar/cirurgia
18.
ACS Macro Lett ; 12(7): 894-900, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37358336

RESUMO

Extending polymer chains results in a positive chain tension, fch, primarily due to conformational restrictions. At the level of individual bonds, however, tension, fb, is either negative or positive and depends on both chain tension and bulk pressure. Typically, the chain and bond tension are assumed to be directly related. In specific systems, however, this dependence may not be intuitive, whereby fch increases while fb decreases; i.e., the entire chain is extended while bonds are compressed. Specifically, increasing the grafting density of a polymer brush results in chain extension along the direction perpendicular to the grafting surface while the underlying bonds are compressed. Similarly, upon compression of polymer networks, the extension of chains oriented in the "free" direction increases while their bonds are getting more compressed. We demonstrate this phenomenon in molecular dynamics simulations and explain it by the fact that the pressure contribution to fb is dominant over a wide range of network deformations and brush grafting densities.

19.
Nat Rev Rheumatol ; 19(12): 790-804, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37923863

RESUMO

Depression is a common and disabling comorbidity in rheumatoid arthritis that not only decreases the likelihood of remission and treatment adherence but also increases the risk of disability and mortality in patients with rheumatoid arthritis. Compelling data that link immune mechanisms to major depressive disorder indicate possible common mechanisms that drive the pathology of the two conditions. Preclinical evidence suggests that pro-inflammatory cytokines, which are prevalent in rheumatoid arthritis, have various effects on monoaminergic neurotransmission, neurotrophic factors and measures of synaptic plasticity. Neuroimaging studies provide insight into the consequences of inflammation on the brain (for example, on neural connectivity), and clinical trial data highlight the beneficial effects of immune modulation on comorbid depression. Major depressive disorder occurs more frequently in patients with rheumatoid arthritis than in the general population, and major depressive disorder also increases the risk of a future diagnosis of rheumatoid arthritis, further highlighting the link between rheumatoid arthritis and major depressive disorder. This Review focuses on interactions between peripheral and central immunobiological mechanisms in the context of both rheumatoid arthritis and major depressive disorder. Understanding these mechanisms will provide a basis for future therapeutic development, not least in depression.


Assuntos
Artrite Reumatoide , Transtorno Depressivo Maior , Humanos , Depressão/etiologia , Depressão/tratamento farmacológico , Depressão/epidemiologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/epidemiologia , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/tratamento farmacológico , Comorbidade , Inflamação
20.
J Int Assoc Provid AIDS Care ; 22: 23259582231186868, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37415442

RESUMO

Despite the prevalence of human immunodeficiency virus (HIV) in Mississippi, access to pre-exposure prophylaxis (PrEP) is mostly limited to urban areas. Remote PrEP care via telemedicine, HIV self-testing, and prescription mail delivery can improve care in underserved communities. This mixed methods study assessed the acceptability and feasibility of using remote PrEP care, compared to alternatives. This consisted of (1) a cross-sectional survey and (2) interviews. PrEP-eligible adults were recruited from community-based organizations across Mississippi while accessing HIV testing between December 2019 and May 2022. Those surveyed (n = 63) indicated the greatest comfort in receiving PrEP via mail delivery (m = 5.14) and telemedicine (m = 4.89) and least comfort at gyms (m = 3.92). Comfort significantly differed between mail delivery and gyms (F = 2.90; P < .01). Those interviewed (n = 26) expressed relatively high comfort with remote PrEP care citing enhanced accessibility, privacy, simplicity, and quality. Remote PrEP services were acceptable and feasible among our sample, thus, should be expanded in Mississippi to address unmet needs.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Adulto , Humanos , Mississippi , Estudos Transversais , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Inquéritos e Questionários , Fármacos Anti-HIV/uso terapêutico , Profilaxia Pré-Exposição/métodos
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