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1.
Clin Infect Dis ; 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34363462

RESUMO

The impact of COVID19 vaccination on viral characteristics of breakthrough infections is unknown. In this prospective cohort study, incidence of SARS-CoV-2 infection decreased following vaccination. Although asymptomatic positive tests were observed following vaccination, higher cycle thresholds, repeat negative tests and inability to culture virus raises questions about their clinical significance.

3.
Sex Transm Dis ; 48(1): 25-31, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810029

RESUMO

BACKGROUND: Preexposure prophylaxis (PrEP) is a highly effective, pharmacologic method of HIV prevention. Despite its safety and efficacy, PrEP prescription remains low in those patients who are at highest risk for HIV infection. One possible reason for this may be the lack of inclusion of PrEP and HIV prevention discussions within the curricula of health professions education. METHODS: An online survey was administered to a cross-sectional sample of future prescribers (osteopathic/allopathic medical and physician assistant students), future nurses, and future pharmacists (n = 2085) in the United States between January and July 2019 to assess and compare awareness of PrEP, PrEP education, PrEP knowledge, and confidence in 2 areas related to PrEP. RESULTS: We show that, overall, awareness of PrEP is high among future health care providers (81.6%), with the future pharmacists reporting the greatest awareness (92.2%; P < 0.001) and more commonly reporting PrEP education (71.0%). Students had mixed knowledge of PrEP, with future pharmacists reporting the highest knowledge of PrEP. Approximately 30% of students in all disciplines reported having low confidence counseling a patient about PrEP and low confidence educating a colleague about PrEP. Knowledge of PrEP was a significant predictor of confidence counseling a patient about PrEP (P < 0.001) and educating a colleague about PrEP (P < 0.001). CONCLUSIONS: This study identifies opportunities to improve and incorporate evidence-based strategies for educating future health care providers about PrEP for HIV prevention within health professions curricula.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Ocupações em Saúde , Humanos , Estudantes , Inquéritos e Questionários , Estados Unidos
5.
Sex Transm Dis ; 47(8): 530-534, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32404857

RESUMO

Physician assistants (PAs) have an important role to play in increasing preexposure prophylaxis (PrEP) prescriptions. We surveyed PAs regarding knowledge of Centers for Disease Control and Prevention guidelines for PrEP and confidence regarding PrEP. Physician assistants in primary care reported more accurate knowledge and higher confidence. However, knowledge and confidence gaps were present among all PAs, regardless of specialty.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Assistentes Médicos , Médicos , Profilaxia Pré-Exposição , Infecções por HIV/prevenção & controle , Humanos , Atenção Primária à Saúde
6.
J Gen Intern Med ; 35(10): 2873-2881, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32080792

RESUMO

BACKGROUND: Daily, oral pre-exposure prophylaxis (PrEP) is an effective and safe prevention strategy for people at risk for HIV. However, prescription of PrEP has been limited for patients at the highest risk. Disparities in PrEP prescription are pronounced among racial and gender minority patients. A significant body of literature indicates that practicing healthcare providers have little awareness and knowledge of PrEP. Very little work has investigated the education about PrEP among health professionals in training. OBJECTIVE: The objective of this study was to compare health professions students' awareness of PrEP and education about PrEP between regions of the US, and to determine if correlations between regional HIV incidence and PrEP use were present. DESIGN: Survey study. PARTICIPANTS: A cross-sectional sample of health professions students (N = 1859) representing future prescribers (MD, DO, PA), pharmacists, and nurses in the US. KEY RESULTS: Overall, 83.4% of students were aware of PrEP, but only 62.2% of fourth-year students indicated they had been taught about PrEP at any time during their training. Education about PrEP was most comprehensive in the Northeastern US, the area with the highest PrEP to need ratio (4.7). In all regions, transgender patients and heterosexual men and women were least likely to be presented in education as PrEP candidates, and men who have sex with men were the most frequently presented. CONCLUSIONS: There are marked differences in education regarding PrEP both between academic programs and regions of the USA.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Homossexualidade Masculina , Humanos , Masculino , Estudantes , Estados Unidos/epidemiologia
11.
Neuron ; 102(4): 801-812.e5, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-30926280

RESUMO

Nociceptive terminals possess the elements for detecting, transmitting, and modulating noxious signals, thus being pivotal for pain sensation. Despite this, a functional description of the transduction process by the terminals, in physiological conditions, has not been fully achieved. Here, we studied how nociceptive terminals in vivo convert noxious stimuli into propagating signals. By monitoring noxious-stimulus-induced Ca2+ dynamics from mouse corneal terminals, we found that initiation of Na+ channel (Nav)-dependent propagating signals takes place away from the terminal and that the starting point for Nav-mediated propagation depends on Nav functional availability. Acute treatment with the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) resulted in a shift of the location of Nav involvement toward the terminal, thus increasing nociceptive excitability. Moreover, a shift of Nav involvement toward the terminal occurs in corneal hyperalgesia resulting from acute photokeratitis. This dynamic change in the location of Nav-mediated propagation initiation could underlie pathological pain hypersensitivity.


Assuntos
Potenciais de Ação , Córnea/inervação , Hiperalgesia/metabolismo , Nociceptores/metabolismo , Terminações Pré-Sinápticas/metabolismo , Canais de Sódio/metabolismo , Animais , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Lesões da Córnea , Interleucina-1beta/farmacologia , Camundongos , Plasticidade Neuronal , Terminações Pré-Sinápticas/efeitos dos fármacos , Canais de Sódio/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Raios Ultravioleta
12.
Cancer Treat Res ; 177: 211-229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30523626

RESUMO

Merkel cell carcinoma (MCC) is a highly aggressive, primary neuroendocrine cancer of the skin. The majority of MCC cases are associated with the recently discovered Merkel cell polyomavirus (MCPyV), while the remaining are caused by ultraviolet (UV) light-induced mutations from excessive sunlight exposure. The risk of developing MCC is much higher in the white population relative to all other races. Approximately 10% of all patients with MCC have some form of immunosuppression including HIV-1/AIDS, chronic inflammatory conditions, solid organ transplantation, or hematological malignancies. The age of onset of MCC is lower and the mortality is higher in immunosuppressed individuals than in immune-competent patients. It is plausible that HIV-1/AIDS predisposes to virus-positive MCC, but it should be noted that HIV-1/AIDS increases the risk for developing of UV-induced skin cancers such as cutaneous squamous cell carcinoma and basal cell carcinoma and therefore may also increase the risk for virus-negative MCC. Surgical management is considered standard of care for localized Merkel cell carcinoma with current recommendations advising a wide local excision of the lesion. Most international guidelines support the use of local adjuvant radiotherapy coupled with tumor staging to improve the frequency of cure. For advanced, metastatic, and recurrent MCC, checkpoint blockade inhibitors targeting PD-1 and PD-L1 have shown remarkable activity including durable long-term. MCC in patients living with HIV-1/AIDS are treated with similar modalities as HIV-1 uninfected individuals with MCC.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Carcinoma de Célula de Merkel/virologia , Carcinoma de Células Escamosas/virologia , HIV-1/isolamento & purificação , Neoplasias Cutâneas/virologia , Síndrome de Imunodeficiência Adquirida/virologia , Carcinoma de Célula de Merkel/terapia , Carcinoma de Células Escamosas/terapia , Infecções por HIV/complicações , Infecções por HIV/virologia , Humanos , Neoplasias Cutâneas/terapia
14.
Surgery ; 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29751965

RESUMO

BACKGROUND: Suspected penicillin allergic individuals receive suboptimal non-ß-lactams for intraoperative prophylaxis which may prolong operations and have negative clinical outcomes. We therefore studied if ß-lactam de-labeling optimized choice of prophylactic antibiotics and improved intraoperative time efficiency. METHODS: A multistep approach was used. It included a risk assessment tool by an allergist, ß-lactam skin testing and oral provocation. To determine the value of de-labeling, we appraised intraoperative antibiotic choices and correlated them with time to first incision. RESULTS: A total of 194 patients were evaluated preoperatively. Four patients were diagnosed ß-lactam allergic on skin testing. Of the remaining 190 skin test negative patients, 146 were ß-lactam challenged. Only 5% reacted and were considered ß-lactam allergic. Cefazolin became the perioperative antibiotic of choice for 77% of patients requiring antibiotic prophylaxis. Only 5 confirmed ß-lactam allergic patients received intraoperative vancomycin. Patients avoiding use of vancomycin saved an average of 22 minutes in operative time. Of the 44 patients not having a ß-lactam challenge, 36 received antibiotics and 18 (50%) of these were prescribed intraoperative cefazolin. CONCLUSION: Using this three step process, almost all of those claiming penicillin allergy were de-labeled. In most patients that were drug challenged, ß-lactam antibiotics became the perioperative drug of choice. In cases where oral challenge was not used in the assessment only 50% were given a ß-lactam. The reduced use of vancomycin minimized delays in initiation of incision time, thus improving operative efficiency. Ultimately, randomized controlled studies are required to objectively determine the effectiveness of this approach.

16.
J Biomed Opt ; 22(7): 76010, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28715544

RESUMO

Pain signals are detected by terminals of nociceptive peripheral fibers situated among the keratinocytes and epithelial cells. Despite being key structures for pain-related stimuli detection and transmission, little is known about the functional organization of terminals. This is mainly due to their minute size, rendering them largely inaccessible by conventional experimental approaches. Here, we report the implementation of an ultrafast optical recording approach for studying cultured neurite terminals, which are readily accessible for assay manipulations. Using this approach, we were able to study capsaicin-induced calcium and sodium dynamics in the nociceptive processes, at a near-action potential time resolution. The approach was sensitive enough to detect differences in latency, time-to-peak, and amplitude of capsaicin-induced ion transients along the terminal neurites. Using this approach, we found that capsaicin evokes distinctive calcium signals along the neurite. At the terminal, the signal was insensitive to voltage-gated sodium channel blockers, and showed slower kinetics and smaller signal amplitudes, compared with signals that were measured further up the neurite. These latter signals were mainly abolished by sodium channel blockers. We propose this ultrafast optical recording approach as a model for studying peripheral terminal signaling, forming a basis for studying pain mechanisms in normal and pathological states.


Assuntos
Capsaicina/farmacologia , Neuritos/efeitos dos fármacos , Potenciais de Ação , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Humanos , Fármacos do Sistema Sensorial/farmacologia , Sódio/metabolismo , Bloqueadores dos Canais de Sódio/farmacologia
17.
Front Mol Neurosci ; 10: 181, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28659757

RESUMO

Peripheral nociceptive neurons encode and convey injury-inducing stimuli toward the central nervous system. In normal conditions, tight control of nociceptive resting potential prevents their spontaneous activation. However, in many pathological conditions the control of membrane potential is disrupted, leading to ectopic, stimulus-unrelated firing of nociceptive neurons, which is correlated to spontaneous pain. We have investigated the role of KV7/M channels in stabilizing membrane potential and impeding spontaneous firing of nociceptive neurons. These channels generate low voltage-activating, noninactivating M-type K+ currents (M-current, IM ), which control neuronal excitability. Using perforated-patch recordings from cultured, rat nociceptor-like dorsal root ganglion neurons, we show that inhibition of M-current leads to depolarization of nociceptive neurons and generation of repetitive firing. To assess to what extent the M-current, acting at the nociceptive terminals, is able to stabilize terminals' membrane potential, thus preventing their ectopic activation, in normal and pathological conditions, we built a multi-compartment computational model of a pseudo-unipolar unmyelinated nociceptive neuron with a realistic terminal tree. The modeled terminal tree was based on the in vivo structure of nociceptive peripheral terminal, which we assessed by in vivo multiphoton imaging of GFP-expressing nociceptive neuronal terminals innervating mice hind paw. By modifying the conductance of the KV7/M channels at the modeled terminal tree (terminal gKV7/M) we have found that 40% of the terminal gKV7/M conductance is sufficient to prevent spontaneous firing, while ~75% of terminal gKV7/M is sufficient to inhibit stimulus induced activation of nociceptive neurons. Moreover, we showed that terminal M-current reduces susceptibility of nociceptive neurons to a small fluctuations of membrane potentials. Furthermore, we simulated how the interaction between terminal persistent sodium current and M-current affects the excitability of the neurons. We demonstrated that terminal M-current in nociceptive neurons impeded spontaneous firing even when terminal Na(V)1.9 channels conductance was substantially increased. On the other hand, when terminal gKV7/M was decreased, nociceptive neurons fire spontaneously after slight increase in terminal Na(V)1.9 conductance. Our results emphasize the pivotal role of M-current in stabilizing membrane potential and hereby in controlling nociceptive spontaneous firing, in normal and pathological conditions.

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