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1.
J Water Health ; 22(6): 1102-1110, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38935460

RESUMO

Ferrate (Fe(VI): HFeO4- /FeO42-), a potent oxidant, has been investigated as an alternative chemical disinfectant in water treatment due to its reduced production of disinfection by-products. In this study, we assessed the disinfecting ability of potassium ferrate against a variety of microorganisms, including waterborne pathogens, under varying pH and water temperature conditions. We presented CT values, a metric of ferrate concentrations (C) and contact time (T), to quantify microbial inactivation rates. Among the tested microorganisms, human adenovirus was the least resistant to ferrate, followed by waterborne bacteria such as Escherichia coli and Vibrio cholerae, and finally, the protozoan parasite Giardia duodenalis. We further investigated the impact of two pH values (7 and 8) and two temperatures (5 and 25 °C) on microbial inactivation rates, observing that inactivation rates increased with lower pH and higher temperature. In addition to showcasing ferrate's capacity to effectively inactivate a range of the tested microorganisms, we offer a ferrate CT table to facilitate the comparison of the effectiveness of various disinfection methods.


Assuntos
Desinfetantes , Giardia lamblia , Temperatura , Concentração de Íons de Hidrogênio , Desinfetantes/farmacologia , Giardia lamblia/efeitos dos fármacos , Adenovírus Humanos/efeitos dos fármacos , Compostos de Potássio/farmacologia , Compostos de Potássio/química , Microbiologia da Água , Desinfecção/métodos , Purificação da Água/métodos , Compostos de Ferro/farmacologia , Compostos de Ferro/química , Humanos , Escherichia coli/efeitos dos fármacos
2.
Br J Cancer ; 123(9): 1377-1386, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32747748

RESUMO

BACKGROUND: BTC is an aggressive disease exacerbated by inflammation and immune suppression. Expansion of immunosuppressive cells occurs in biliary tract cancer (BTC), yet the role of BTC-derived cytokines in this process is unclear. METHODS: Activated signalling pathways and cytokine production were evaluated in a panel of human BTC cell lines. Human peripheral blood mononuclear cells (PBMCs) were cultured with BTC supernatants, with and without cytokine neutralising antibodies, and analysed by flow cytometry or immunoblot. A human BTC tissue microarray (TMA, n = 69) was stained for IL-6, GM-CSF, and CD33+S100a9+ cells and correlated with clinical outcomes. RESULTS: Immunomodulatory factors (IL-6, GM-CSF, MCP-1) were present in BTC supernatants. BTC supernatants expanded CD33dimCD11b+HLA-DRlow/- myeloid-derived suppressor cells (MDSCs) from human PBMCs. Neutralisation of IL-6 and GM-CSF in BTC supernatants inhibited activation of STAT3/5, respectively, in PBMCs, with heterogeneous effects on MDSC expansion in vitro. Staining of a BTC TMA revealed a positive correlation between IL-6 and GM-CSF, with each cytokine and more CD33+S100a9+ cells. Increased CD33+S100a9+ staining positively correlated with higher tumour grade, differentiation and the presence of satellite lesions. CONCLUSION: BTC-derived factors promote suppressive myeloid cell expansion, and higher numbers of CD33+S100a9+ cells in resectable BTC tumours correlates with more aggressive disease.


Assuntos
Neoplasias do Sistema Biliar/metabolismo , Neoplasias do Sistema Biliar/patologia , Proliferação de Células/efeitos dos fármacos , Citocinas/farmacologia , Células Supressoras Mieloides/efeitos dos fármacos , Calgranulina B/metabolismo , Contagem de Células , Células Cultivadas , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Humanos , Ativação Linfocitária/efeitos dos fármacos , Células Mieloides/efeitos dos fármacos , Células Mieloides/patologia , Células Mieloides/fisiologia , Células Supressoras Mieloides/patologia , Células Supressoras Mieloides/fisiologia , Gradação de Tumores , Invasividade Neoplásica , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo
3.
Crit Care ; 24(1): 561, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948243

RESUMO

BACKGROUND: Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications. METHODS: We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications. RESULTS: A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49-64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not. CONCLUSION: Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.


Assuntos
Infecções por Coronavirus/complicações , Estado Terminal , Hemorragia/etiologia , Pneumonia Viral/complicações , Trombose/etiologia , Betacoronavirus , COVID-19 , Infecções por Coronavirus/terapia , Feminino , Hemorragia/terapia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Estudos Retrospectivos , SARS-CoV-2 , Tromboelastografia , Trombose/terapia , Reino Unido
4.
Opt Express ; 25(13): 13990-14007, 2017 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-28788985

RESUMO

We assess several widely used vector models of a Gaussian laser beam in the context of more accurate vector diffraction integration. For the analysis, we present a streamlined derivation of the vector fields of a uniformly polarized beam reflected from an ideal parabolic mirror, both inside and outside of the resulting focus. This exact solution to Maxwell's equations, first developed in 1920 by V. S. Ignatovsky, is highly relevant to high-intensity laser experiments since the boundary conditions at a focusing optic dictate the form of the focus in a manner analogous to a physical experiment. In contrast, many models simply assume a field profile near the focus and develop the surrounding vector fields consistent with Maxwell's equations. In comparing the Ignatovsky result with popular closed-form analytic vector models of a Gaussian beam, we find that the relatively simple model developed by Erikson and Singh in 1994 provides good agreement in the paraxial limit. Models involving a Lax expansion introduce a divergences outside of the focus while providing little if any improvement in the focal region. Extremely tight focusing produces a somewhat complicated structure in the focus, and requires the Ignatovsky model for accurate representation.

5.
Opt Lett ; 41(4): 689-92, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26872164

RESUMO

We present calibrated measurements of single-photon Thomson scattering from free electrons driven by a laser with intensity 1018 W/cm2. The measurements demonstrate that individual electrons radiate with the strength of point emitters, even when their wave packets spread to the scale of the driving-laser wavelength. The result agrees with predictions of quantum electrodynamics.

6.
Parasitol Res ; 114(12): 4655-67, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26358104

RESUMO

Surveillance monitoring for microbial water quality typically involves collecting single discrete grab samples for analyzing only one contaminant. While informative, current approaches suffer from poor recoveries and only provide a limited snapshot of the microbial contaminants only at the time of collection. To overcome these limitations, bivalves have been proposed as effective biosentinels of water quality particularly for their ability to efficiently concentrate and retain microbial contaminants for long periods of time. In this study, we examined the use of indigenous blue mussels (Mytilus spp.) as biosentinels to monitor for the presence of Toxoplasma gondii and Cryptosporidium water. An efficient method to extract oocyst DNA from various mussel tissues followed by PCR-based detection of these pathogens was developed, which resulted in the detection down to 10 oocysts. This method was then used to conduct a small survey in Point Lobos and Morro Bay, California to determine prevalence T. gondii and Cryptosporidium. Results revealed that mussels from Morro Bay were contaminated with T. gondii (33 %), while mussels from Point Lobos were contaminated with T. gondii (54 %) and Cryptosporidium (26.9 %) oocysts. Phylogenetic analysis using the SSU rRNA gene identified two novel Cryptosporidium parvum-like genotypes. Overall, this study demonstrated the application of using native California Mytilus spp. as biosentinels for pathogen contamination along the central California shorelines. More importantly, T. gondii and Cryptosporidium were found at higher prevalence rates in Morro Bay and in Point Lobos, an area not previously reported to be contaminated with these pathogens.


Assuntos
Cryptosporidium parvum/isolamento & purificação , Cryptosporidium/isolamento & purificação , Monitoramento Ambiental/métodos , Mytilus edulis/parasitologia , Água do Mar/parasitologia , Toxoplasma/isolamento & purificação , Animais , California , Cryptosporidium/classificação , Cryptosporidium/genética , Cryptosporidium/fisiologia , Cryptosporidium parvum/classificação , Cryptosporidium parvum/genética , Cryptosporidium parvum/fisiologia , Dados de Sequência Molecular , Mytilus , Mytilus edulis/genética , Filogenia , Reação em Cadeia da Polimerase/métodos , Frutos do Mar/parasitologia , Toxoplasma/classificação , Toxoplasma/genética , Toxoplasma/fisiologia
7.
J Environ Qual ; 44(1): 265-74, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25602342

RESUMO

Biosolids are nutrient-rich organic residuals that are currently used to amend soils for food production. Treatment requirements to inactivate pathogens for production of Class A biosolids are energy intensive. One less energy intensive alternative is to treat biosolids to Class B standards, but it could result in higher pathogen loads. Quantitative microbial risk assessments models have been developed on land application of Class B biosolids but contain many uncertainties because of limited data on specific pathogen densities and the use of fecal indicator organisms as accurate surrogates of pathogen loads. To address this gap, a 12-mo study of the levels and relationships between , , and human adenovirus (HAdV) with fecal coliform, somatic, and F-RNA coliphage levels in Class B biosolids from nine wastewater treatment plants throughout the United States was conducted. Results revealed that fecal coliform, somatic, and F-RNA coliphage densities were consistent throughout the year. More important, results revealed that HAdV ( = 2.5 × 10 genome copies dry g) and ( = 4.14 × 10 cysts dry g) were in all biosolids samples regardless of treatment processes, location, or season. oocysts were also detected (38% positive; range: 0-1.9 × 10 oocysts dry g), albeit sporadically. Positive correlations among three fecal indicator organisms and HAdV, but not protozoa, were also observed. Overall, this study reveals that high concentrations of enteric pathogens (e.g., , , and HAdV) are present in biosolids throughout the United States. Microbial densities found can further assist management and policymakers in establishing more accurate risk assessment models associated with land application of Class B biosolids.

8.
Appl Environ Microbiol ; 79(5): 1676-88, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23291550

RESUMO

Predictive models, based on environmental and water quality variables, have been used to improve the timeliness and accuracy of recreational water quality assessments, but their effectiveness has not been studied in inland waters. Sampling at eight inland recreational lakes in Ohio was done in order to investigate using predictive models for Escherichia coli and to understand the links between E. coli concentrations, predictive variables, and pathogens. Based upon results from 21 beach sites, models were developed for 13 sites, and the most predictive variables were rainfall, wind direction and speed, turbidity, and water temperature. Models were not developed at sites where the E. coli standard was seldom exceeded. Models were validated at nine sites during an independent year. At three sites, the model resulted in increased correct responses, sensitivities, and specificities compared to use of the previous day's E. coli concentration (the current method). Drought conditions during the validation year precluded being able to adequately assess model performance at most of the other sites. Cryptosporidium, adenovirus, eaeA (E. coli), ipaH (Shigella), and spvC (Salmonella) were found in at least 20% of samples collected for pathogens at five sites. The presence or absence of the three bacterial genes was related to some of the model variables but was not consistently related to E. coli concentrations. Predictive models were not effective at all inland lake sites; however, their use at two lakes with high swimmer densities will provide better estimates of public health risk than current methods and will be a valuable resource for beach managers and the public.


Assuntos
Carga Bacteriana , Escherichia coli/isolamento & purificação , Água Doce/microbiologia , Adenoviridae/isolamento & purificação , Clima , Cryptosporidium/isolamento & purificação , Lagos , Modelos Estatísticos , Ohio , Salmonella/isolamento & purificação , Sensibilidade e Especificidade , Shigella/isolamento & purificação
9.
Appl Environ Microbiol ; 79(4): 1342-52, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23263948

RESUMO

Bacterial indicators are used to indicate increased health risk from pathogens and to make beach closure and advisory decisions; however, beaches are seldom monitored for the pathogens themselves. Studies of sources and types of pathogens at beaches are needed to improve estimates of swimming-associated health risks. It would be advantageous and cost-effective, especially for studies conducted on a regional scale, to use a method that can simultaneously filter and concentrate all classes of pathogens from the large volumes of water needed to detect pathogens. In seven recovery experiments, stock cultures of viruses and protozoa were seeded into 10-liter lake water samples, and concentrations of naturally occurring bacterial indicators were used to determine recoveries. For the five filtration methods tested, the highest median recoveries were as follows: glass wool for adenovirus (4.7%); NanoCeram for enterovirus (14.5%) and MS2 coliphage (84%); continuous-flow centrifugation (CFC) plus Virocap (CFC+ViroCap) for Escherichia coli (68.3%) and Cryptosporidium (54%); automatic ultrafiltration (UF) for norovirus GII (2.4%); and dead-end UF for Enterococcus faecalis (80.5%), avian influenza virus (0.02%), and Giardia (57%). In evaluating filter performance in terms of both recovery and variability, the automatic UF resulted in the highest recovery while maintaining low variability for all nine microorganisms. The automatic UF was used to demonstrate that filtration can be scaled up to field deployment and the collection of 200-liter lake water samples.


Assuntos
Bactérias/isolamento & purificação , Cryptosporidium/isolamento & purificação , Filtração/métodos , Água Doce/microbiologia , Giardia/isolamento & purificação , Vírus/isolamento & purificação , Água Doce/parasitologia , Água Doce/virologia , Reprodutibilidade dos Testes
10.
JCI Insight ; 8(8)2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-36881480

RESUMO

This study aimed to enhance antitumor immune responses to pancreatic cancer via Ab-based blockade of IL-6 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Mice bearing s.c. or orthotopic pancreatic tumors were treated with blocking Abs to IL­6 and/or CTLA-4. In both tumor models, dual IL-6 and CTLA-4 blockade significantly inhibited tumor growth. Additional investigations revealed that dual therapy induced an overwhelming infiltration of T cells into the tumor as well as changes in CD4+ T cell subsets. Dual blockade therapy elicited CD4+ T cells to secrete increased IFN-γ in vitro. Likewise, in vitro stimulation of pancreatic tumor cells with IFN-γ profoundly increased tumor cell production of CXCR3-specific chemokines, even in the presence of IL-6. In vivo blockade of CXCR3 prevented orthotopic tumor regression in the presence of the combination treatment, demonstrating a dependence on the CXCR3 axis for antitumor efficacy. Both CD4+ and CD8+ T cells were required for the antitumor activity of this combination therapy, as their in vivo depletion via Abs impaired outcomes. These data represent the first report to our knowledge of IL-6 and CTLA­4 blockade as a means to regress pancreatic tumors with defined operative mechanisms of efficacy.


Assuntos
Interleucina-6 , Neoplasias Pancreáticas , Animais , Camundongos , Linfócitos T CD8-Positivos , Antígeno CTLA-4 , Interleucina-6/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Subpopulações de Linfócitos T
11.
J Immunother Precis Oncol ; 5(4): 105-117, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36483588

RESUMO

Immunotherapies for the treatment of solid tumors continue to develop in preclinical and clinical research settings. Unfortunately, for many patients the tumor fails to respond or becomes resistant to therapies such as checkpoint inhibitors (CPIs) targeting programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4). In many cancers, failed response to CPIs can be attributed to poor T cell infiltration, dominant immunosuppression, and exhausted immune responses. In gastrointestinal (GI) cancers T cell infiltration can be dismal, with several reports finding that CD8+ T cells compose less than 2% of all cells within the tumor. Organized aggregates of lymphocytes, antigen-presenting cells, and vessels, together termed tertiary lymphoid structures (TLSs), are hypothesized to be a major source of T cells within solid tumors. The intratumoral formation of these organized immune centers appears to rely on intricate cytokine and chemokine signaling to heterogeneous cell populations such as B and T cells, innate lymphoid cells, fibroblasts, and dendritic cells. In GI cancers, the presence and density of TLSs provide prognostic value for predicting outcome and survival. Further, TLS presence and density associates with favorable responses to CPIs in many cancers. This review highlights the prognostic value of TLSs in GI cancers, the role of the homeostatic cytokine interleukin-7 (IL-7) in TLS formation, and the induction of TLSs in solid tumors by novel therapeutics.

12.
Front Oncol ; 12: 836845, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433480

RESUMO

Autoimmune toxicities, while common following treatment with cancer immunotherapies, are not well-characterized in patients treated with BRAF/MEK inhibitors. Emerging data suggest that autoimmune effects may be linked with superior responses to both treatment modalities; however, there is little evidence describing mechanisms of immune-related toxicity for patients on BRAF/MEK inhibitors. Here we describe the experience of a 59-year-old HLA-A2, A29, B27-positive male with recurrent/metastatic melanoma. After progression on checkpoint inhibitor therapy, he was treated with dabrafenib/trametinib followed by encorafenib/binimetinib, which were well-tolerated and resulted in a complete response. Eighteen months into BRAF/MEK inhibitor therapy, and three months after initially finding a complete response, he developed a series of sudden-onset, severe toxicities: namely, bilateral panuveitis, cytopenias, joint pain, skin rash, hypercalcemia, and interstitial nephritis, which led to BRAF/MEKi cessation. Immunological analyses revealed induction of a peripheral type-17 cytokine signature characterized by high IL-23, IL-6, IL-10, IL-17A/F, IL-1ß, and IL-21 among other cytokines in plasma corresponding with the height of symptoms. These findings highlight a novel instance of delayed autoimmune-like reaction to BRAF/MEK inhibition and identify a possible role for Th/Tc17 activation in their pathogenesis thus warranting future clinical and immunological characterization.

13.
J Immunother Cancer ; 10(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35017148

RESUMO

BACKGROUND: Adoptive T cell transfer (ACT) therapy improves outcomes in patients with advanced malignancies, yet many individuals relapse due to the infusion of T cells with poor function or persistence. Toll-like receptor (TLR) agonists can invigorate antitumor T cell responses when administered directly to patients, but these responses often coincide with toxicities. We posited that TLR agonists could be repurposed ex vivo to condition T cells with remarkable potency in vivo, circumventing TLR-related toxicity. METHODS: In this study we investigated how tumor-specific murine CD8+ T cells and human tumor infiltrating lymphocytes (TILs) are impacted when expanded ex vivo with the TLR9 agonist CpG. RESULTS: Herein we reveal a new way to reverse the tolerant state of adoptively transferred CD8+ T cells against tumors using TLR-activated B cells. We repurposed the TLR9 agonist, CpG, commonly used in the clinic, to bolster T cell-B cell interactions during expansion for ACT. T cells expanded ex vivo from a CpG-treated culture demonstrated potent antitumor efficacy and prolonged persistence in vivo. This antitumor efficacy was accomplished without in vivo administration of TLR agonists or other adjuvants of high-dose interleukin (IL)-2 or vaccination, which are classically required for effective ACT therapy. CpG-conditioned CD8+ T cells acquired a unique proteomic signature hallmarked by an IL-2RαhighICOShighCD39low phenotype and an altered metabolic profile, all reliant on B cells transiently present in the culture. Likewise, human TILs benefitted from expansion with CpG ex vivo, as they also possessed the IL-2RαhighICOShighCD39low phenotype. CpG fostered the expansion of potent CD8+ T cells with the signature phenotype and antitumor ability via empowering a direct B-T cell interaction. Isolated B cells also imparted T cells with the CpG-associated phenotype and improved tumor immunity without the aid of additional antigen-presenting cells or other immune cells in the culture. CONCLUSIONS: Our results demonstrate a novel way to use TLR agonists to improve immunotherapy and reveal a vital role for B cells in the generation of potent CD8+ T cell-based therapies. Our findings have immediate implications in the clinical treatment of advanced solid tumors.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunoterapia Adotiva/métodos , Melanoma/tratamento farmacológico , Animais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
14.
Nat Commun ; 13(1): 6418, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36302761

RESUMO

A paucity of effector T cells within tumors renders pancreatic ductal adenocarcinoma (PDAC) resistant to immune checkpoint therapies. While several under-development approaches target immune-suppressive cells in the tumor microenvironment, there is less focus on improving T cell function. Here we show that inhibiting vasoactive intestinal peptide receptor (VIP-R) signaling enhances anti-tumor immunity in murine PDAC models. In silico data mining and immunohistochemistry analysis of primary tumors indicate overexpression of the neuropeptide vasoactive intestinal peptide (VIP) in human PDAC tumors. Elevated VIP levels are also present in PDAC patient plasma and supernatants of cultured PDAC cells. Furthermore, T cells up-regulate VIP receptors after activation, identifying the VIP signaling pathway as a potential target to enhance T cell function. In mouse PDAC models, VIP-R antagonist peptides synergize with anti-PD-1 antibody treatment in improving T cell recruitment into the tumors, activation of tumor-antigen-specific T cells, and inhibition of T cell exhaustion. In contrast to the limited single-agent activity of anti-PD1 antibodies or VIP-R antagonist peptides, combining both therapies eliminate tumors in up to 40% of animals. Furthermore, tumor-free mice resist tumor re-challenge, indicating anti-cancer immunological memory generation. VIP-R signaling thus represents a tumor-protective immune-modulatory pathway that is targetable in PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Peptídeo Intestinal Vasoativo/farmacologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Receptores de Peptídeo Intestinal Vasoativo , Transdução de Sinais , Microambiente Tumoral , Neoplasias Pancreáticas
15.
Arch Sex Behav ; 40(2): 273-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19330436

RESUMO

Recent studies show that Viagra and methamphetamine use are associated with unprotected anal intercourse among men who have sex with men (MSM). In Long Beach, California, we have reported on an association between Viagra use and the use of amphetamines during sex. The current research investigated the use of both Viagra and amphetamine in men in Long Beach, California. Data on 1,839 men recruited into HIV prevention and testing programs were collected using the Risk Behavior Assessment. A generalized logit model was constructed comparing ever having used both amphetamine and Viagra together and separately, as compared to never having used either (referent). Men who used both methamphetamine and Viagra showed a significantly higher prevalence of hepatitis B, syphilis, and HIV compared to those who used only one or neither drug. Of the 1,794 complete cases, 11.1% (199/1794) had used both amphetamine and Viagra. Of 20 potential risk and protective factors for use of amphetamine and Viagra, 12 were significant predictors: ever used gamma-hydroxybutyrate (GHB), ever used cocaine, ever used ecstasy, being infected with HIV, race=White compared to other, ever having hepatitis B, ever using crack, ever given money to have sex, living in a hotel, ever been in drug treatment, and ever using heroin. The protective factor was being heterosexual. Viagra use was associated with insertive, and methamphetamine was associated with receptive, anal intercourse. GHB use appears to play a more important role than previously thought.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Metanfetamina , Inibidores da Fosfodiesterase 5 , Piperazinas , Assunção de Riscos , Comportamento Sexual/estatística & dados numéricos , Sulfonas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Distribuição de Qui-Quadrado , Infecções por HIV/epidemiologia , Hepatite B/epidemiologia , Homossexualidade Masculina/psicologia , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Prevalência , Purinas , Fatores de Risco , Comportamento Sexual/psicologia , Parceiros Sexuais , Citrato de Sildenafila , Sífilis/epidemiologia
16.
Water (Basel) ; 13(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34804602

RESUMO

Facing challenges in water demands and population size, particularly in the water-scarce regions in the United States, the reuse of treated municipal wastewater has become a viable potential to relieve the ever-increasing demands of providing water for (non-)potable use. The objectives of this study were to assess microbial quality of reclaimed water and to investigate treatability of microorganisms during different treatment processes. Raw and final treated effluent samples from three participating utilities were collected monthly for 16 months and analyzed for various microbial pathogens and fecal indicator organisms. Results revealed that the detectable levels of microbial pathogens tested were observed in the treated effluent samples from all participating utilities. Log10 reduction values (LRVs) of Cryptosporidium oocysts and Giardia cysts were at least two orders of magnitude lower than those of human adenovirus and all fecal indicator organisms except for aerobic endospores, which showed the lowest LRVs. The relatively higher LRV of the indicator organisms such as bacteriophages suggested that these microorganisms are not good candidates of viral indicators of human adenovirus during wastewater treatment processes. Overall, this study will assist municipalities considering the use of wastewater effluent as another source of drinking water by providing important data on the prevalence, occurrence, and reduction of waterborne pathogens in wastewater. More importantly, the results from this study will aid in building a richer microbial occurrence database that can be used towards evaluating reuse guidelines and disinfection practices for water reuse practices.

17.
Mol Cancer Ther ; 20(1): 150-160, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33037138

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has a prominent fibrotic stroma, which is a result of interactions between tumor, immune and pancreatic stellate cells (PSC), or cancer-associated fibroblasts (CAF). Targeting inflammatory pathways present within the stroma may improve access of effector immune cells to PDAC and response to immunotherapy. Heat shock protein-90 (Hsp90) is a chaperone protein and a versatile target in pancreatic cancer. Hsp90 regulates a diverse array of cellular processes of relevance to both the tumor and the immune system. However, to date the role of Hsp90 in PSC/CAF has not been explored in detail. We hypothesized that Hsp90 inhibition would limit inflammatory signals, thereby reprogramming the PDAC tumor microenvironment to enhance sensitivity to PD-1 blockade. Treatment of immortalized and primary patient PSC/CAF with the Hsp90 inhibitor XL888 decreased IL6, a key cytokine that orchestrates immune changes in PDAC at the transcript and protein level in vitro XL888 directly limited PSC/CAF growth and reduced Jak/STAT and MAPK signaling intermediates and alpha-SMA expression as determined via immunoblot. Combined therapy with XL888 and anti-PD-1 was efficacious in C57BL/6 mice bearing syngeneic subcutaneous (Panc02) or orthotopic (KPC-Luc) tumors. Tumors from mice treated with both XL888 and anti-PD-1 had a significantly increased CD8+ and CD4+ T-cell infiltrate and a unique transcriptional profile characterized by upregulation of genes associated with immune response and chemotaxis. These data demonstrate that Hsp90 inhibition directly affects PSC/CAF in vitro and enhances the efficacy of anti-PD-1 blockade in vivo.


Assuntos
Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Compostos Azabicíclicos/farmacologia , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/genética , Células Estreladas do Pâncreas/efeitos dos fármacos , Células Estreladas do Pâncreas/metabolismo , Fenótipo , Ácidos Ftálicos/farmacologia , Receptor de Morte Celular Programada 1/metabolismo , Resultado do Tratamento , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Appl Environ Microbiol ; 76(15): 5140-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20543052

RESUMO

The effect of UV exposure on Toxoplasma gondii oocysts has not been completely defined for use in water disinfection. This study evaluated UV-irradiated oocysts by three assays: a SCID mouse bioassay, an in vitro T. gondii oocyst plaque (TOP) assay, and a quantitative reverse transcriptase real-time PCR (RT-qPCR) assay. The results from the animal bioassay show that 1- and 3-log(10) inactivation is achieved with 4 mJ/cm(2) UV and 10 mJ/cm(2) low-pressure UV, respectively. TOP assay results, but not RT-qPCR results, correlate well with bioassay results. In conclusion, a 3-log(10) inactivation of T. gondii oocysts is achieved by 10-mJ/cm(2) low-pressure UV, and the in vitro TOP assay is a promising alternative to the mouse bioassay.


Assuntos
Viabilidade Microbiana/efeitos da radiação , Oocistos/efeitos da radiação , Parasitologia/métodos , Toxoplasma/efeitos da radiação , Animais , Bioensaio/métodos , Técnicas de Cultura de Células/métodos , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Toxoplasmose Animal/parasitologia , Purificação da Água/métodos
19.
Appl Opt ; 49(9): 1581-5, 2010 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-20300153

RESUMO

We use a laser high-harmonics-based extreme-ultraviolet (EUV) polarimeter to determine the optical constants of elemental uranium in the wavelength range from 10 to 47 nm. The constants are extracted from the measured ratio of p-polarized to s-polarized reflectance from a thin uranium film deposited in situ. The film thickness is inferred from a spectroscopic ellipsometry measurement of the sample after complete oxidation in room air. Uranium has been used as a high-reflectance material in the EUV. However, difficulties with oxidation prevented its careful characterization previous to this study. We find that measured optical constants for uranium vary significantly from previous estimates.

20.
Rev Sci Instrum ; 91(3): 033320, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32259921

RESUMO

We report an all-solid-state gamma-ray scintillation detector comprised of a NaI(Tl) crystal and a scientific-grade CMOS camera. After calibration, this detector exhibits excellent linearity over more than three decades of activity levels ranging from 10 mCi to 400 nCi. Because the detector is not counting pulses, dead-time correction is not required. Compared to systems that use a photomultiplier tube, this detector has similar sensitivity and noise characteristics on short time scales. On longer time scales, we measure drifts of a few percent over several days, which can be accommodated through regular calibration. Using this detector, we observe that when high activity sources are brought into close proximity to the NaI crystal, several minutes are required for the measured signal to achieve a steady state.

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