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Infecciones por VIH , Hidradenitis Supurativa , Índice de Severidad de la Enfermedad , Humanos , Hidradenitis Supurativa/epidemiología , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/inmunología , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Masculino , Femenino , Adulto , Persona de Mediana Edad , Comorbilidad , Carga Viral , Coinfección/epidemiología , Coinfección/virologíaRESUMEN
From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to antihistamines alone. The most common antihistamine found in all these reported deaths is diphenhydramine, a ubiquitous, over-the-counter and clinically important medication. Currently, there is no antidote for diphenhydramine overdose. This review summarizes the adverse health effects and current emergency medicine treatments for diphenhydramine. Several emergency medicine case reports are reviewed, and the efficacy and outcomes of a variety of treatments are compared. The treatments reviewed include the more traditional antihistamine overdose therapeutics physostigmine and sodium bicarbonate, as well as newer ones such as donepezil, dexmedetomidine, and lipid emulsion therapy. We conclude that more study is needed to determine the ideal therapeutic approach to treating antihistamine overdoses.
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Most rod-shaped bacteria elongate by inserting new cell wall material into the inner surface of the cell sidewall. This is performed by class A penicillin binding proteins (PBPs) and a highly conserved protein complex, the elongasome, which moves processively around the cell circumference and inserts long glycan strands that act as barrel-hoop-like reinforcing structures, thereby giving rise to a rod-shaped cell. However, it remains unclear how elongasome synthesis dynamics and termination events are regulated to determine the length of these critical cell-reinforcing structures. To address this, we developed a method to track individual elongasome complexes around the entire circumference of Bacillus subtilis cells for minutes-long periods using single-molecule fluorescence microscopy. We found that the B. subtilis elongasome is highly processive and that processive synthesis events are frequently terminated by rapid reversal or extended pauses. We found that cellular levels of RodA regulate elongasome processivity, reversal and pausing. Our single-molecule data, together with stochastic simulations, show that elongasome dynamics and processivity are regulated by molecular motor tug-of-war competition between several, likely two, oppositely oriented peptidoglycan synthesis complexes associated with the MreB filament. Altogether these results demonstrate that molecular motor tug-of-war is a key regulator of elongasome dynamics in B. subtilis, which likely also regulates the cell shape via modulation of elongasome processivity.
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Bacillus subtilis , Proteínas Bacterianas , Pared Celular , Proteínas de Unión a las Penicilinas , Bacillus subtilis/metabolismo , Bacillus subtilis/genética , Pared Celular/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas de Unión a las Penicilinas/metabolismo , Proteínas de Unión a las Penicilinas/genética , Peptidoglicano/metabolismo , Peptidoglicano/biosíntesis , Microscopía Fluorescente , Imagen Individual de Molécula , Proteínas Motoras Moleculares/metabolismo , Proteínas Motoras Moleculares/genéticaRESUMEN
Performing artists, such as dancers, singers, actors and musicians, rely on their physical bodies to successfully execute their artforms. However, literature regarding dermatologic conditions that impact dancers is lacking. An anonymous REDCap® secure survey was distributed by email to Dance Majors, Dance Minors, and Dance Instructors/Professors at five Virginia undergraduate institutions. Responses regarding demographics, style of dance, and dermatological diseases were recorded over a 2 month period. When asked about developing skin disease, 57 (59%) of survey participants reported experiencing skin diseases, such as acne, eczema, hyperhidrosis, and plantar warts. When asked about skin diseases exacerbated or believed to be caused from dancing, 56 (59%) reported blisters, callouses, skin splitting, nail/foot infection, ingrown nails, and floor burns. This study demonstrates two main findings: dancing may exacerbate current skin disorders and some skin conditions may be caused by dancing. Additionally, the common practice of dancing barefoot likely contributes to the development of certain skin conditions. Limitations include sample size, response bias, and lack of validation of the survey.
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Baile , Verrugas , Humanos , Pie , Baile/fisiología , Encuestas y Cuestionarios , Examen Físico , Verrugas/epidemiologíaRESUMEN
Purpose: Endoscopic transsphenoidal surgery (ETSS) is an increasingly utilized approach for resection of pituitary tumors. Prior studies have evaluated preoperative tumor size, location, and extent as prognostic factors for surgical resection. There is little data on the relationship between preoperative pituitary tumor radiographic morphology and surgical outcomes. Study Design: Retrospective longitudinal study. Setting: Single tertiary care institution. Subjects and Methods: Preoperative magnetic resonance imaging and computed tomography scans from patients undergoing ETSS for pituitary tumor resections from 2007 to 2017 were retrospectively evaluated. A neuroradiologist classified these pituitary tumors into six morphologic groups, each defined by volume, dimensions, extension, and shape. Surgical difficulty, rates of incomplete resection, and postoperative complications were then stratified in relation to the morphologic groups. Results: Pituitary tumors from 131 patients were classified from preoperative imaging into six characteristic morphologies: (1) microtumor, (2) round, (3) transverse oblong, (4) superior-inferior oblong, (5) bilobed, and (6) large lobulated. Tumors that were characterized with the large lobulated, bilobed, and transverse oblong morphologies correlated with higher rates of postoperative evidence of residual tumor (70%, 36%, and 47%, respectively, all P < 0.002). Likewise, large lobulated, bilobed, and transverse oblong morphologies were also associated with intraoperative cerebrospinal fluid leaks (70%, 31%, and 35%, respectively, all P < 0.05). Conclusions: We describe a novel descriptive system for the morphology of pituitary tumors that can be determined from preoperative imaging. Different tumor morphologic groups are associated with varying degrees of gross tumor resection, complications, and surgical difficulty. Utilizing pituitary tumor morphology may aid surgeons in planning the extent of resection, need for complex closure, and patient counseling.
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Kratom (Mitragyna speciosa) is a tropical tree that is indigenous to Southeast Asia. Kratom leaf products have been used in traditional folk medicine for their unique combination of stimulant and opioid-like effects. Kratom is being increasingly used in the West for its reputed benefits in the treatment of pain, depression, and opioid use disorder (OUD). Recent studies from the United States Food and Drug Administration (FDA, Silver Spring, MD, USA) and our laboratory have shown that many kratom products being sold in the United States are contaminated with potentially hazardous levels of lead (Pb). In this commentary, we discuss the public health implications of the presence of Pb in kratom products, particularly as they relate to the predicted levels of Pb exposure among kratom users. We also considered the specific toxic effects of Pb and how they might relate to the known physiologic and toxicologic effects of kratom. Finally, we consider the possible sources of Pb in kratom products and suggest several areas for research on this issue.
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Type II diabetes mellitus (T2DM) is characterized by insulin resistance, ß-cell dysfunction and hyperglycemia. In addition to well known risk factors such as lifestyle and genetic risk score, accumulation of environmental toxicants in organs relevant to glucose metabolism is increasingly recognized as additional risk factors for T2DM. Here, we describe the development of an in vivo oral cadmium (Cd) exposure model. It was shown that oral Cd exposure in drinking water followed by washout and high fat diet (HFD) in C57BL/6N mice results in islet Cd bioaccumulation comparable to that found in native human islets while mitigating the anorexic effects of Cd to achieve the same weight gain required to induce insulin resistance as in Cd naïve control mice. Inter individual variation in plasma glucose and insulin levels as well as islet Cd bioaccumulation was observed in both female and male mice. Regression analysis showed an inverse correlation between islet Cd level and plasma insulin following a glucose challenge in males but not in females. This finding highlights the need to account for inter individual target tissue Cd concentrations when interpreting results from in vivo Cd exposure models. No effect of Cd on insulin secretion was observed in islets ex vivo, highlighting differences between in vivo and ex vivo cadmium exposure models. In summary, our oral in vivo Cd exposure-washout with HFD model resulted in islet Cd bioaccumulation that is relevant in the context of environmental cadmium exposure in humans. Here, we showed that islet Cd bioaccumulation is associated with complex cadmium-mediated changes in glucose clearance and ß-cell function. The model described here will serve as a useful tool to further examine the relationship between Cd exposure, islet Cd bioaccumulation, dysglycemia and their underlying mechanisms.
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Intoxicación por Cadmio , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Insulinas , Islotes Pancreáticos , Animales , Cadmio/metabolismo , Cadmio/toxicidad , Diabetes Mellitus Tipo 2/metabolismo , Dieta Alta en Grasa/efectos adversos , Femenino , Glucosa/metabolismo , Insulina/metabolismo , Insulinas/metabolismo , Insulinas/farmacología , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Studies show an association between cadmium (Cd) exposure and prediabetes or type II diabetes mellitus. We have previously reported that Cd causes decreased levels of serum leptin in rats following 12 weeks of daily Cd dosing (0.6 mg/kg/b.w./day). Since leptin plays an important role in metabolism, we examined the effects of Cd on rats and db/db mice, which are deficient in leptin receptor activity. We gave rats and mice daily subcutaneous injections of saline (control) or CdCl2 at a dose of 0.6 mg/kg of Cd for 2 weeks, followed by 2 weeks of no dosing. At the end of the 4-week study, exposure to Cd resulted in a more rapid increase in blood glucose levels following an oral glucose tolerance test in db/db vs. lean mice. During the two weeks of no Cd dosing, individual rat bodyweight gain was greater (p ≤ 0.05) in Cd-treated animals. At this time point, the combined epididymal and retroperitoneal fat pad weight was significantly greater (p ≤ 0.05) in the Cd-treated lean mice compared to saline-treated controls. Although this pilot study had relatively low N values (4 per treatment group for mice and 6 for rats) the results show that clinically relevant levels of Cd exposure resulted in diabetogenic as well as obesogenic effects.
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Type II diabetes mellitus (T2DM) is a multifactorial disease process that is characterized by insulin resistance and impairment of insulin-producing pancreatic islets. There is evidence that environmental exposure to cadmium contributes to the development of T2DM. The presence of cadmium in human islets from the general population and the uptake of cadmium in ß-cells have been reported. To identify cadmium-mediated changes in gene expression and molecular regulatory networks in pancreatic islets, we performed next-generation RNA-Sequencing (RNA-Seq) in islets following either in vivo (1 mM CdCl2 in drinking water) or ex-vivo (0.5 µM CdCl2) exposure. Both exposure regiments resulted in islet cadmium concentrations that are comparable to those found in human islets from the general population. 6-week in vivo cadmium exposure upregulates the expression of five genes: Synj2, Gjb1, Rbpjl, Try5 and 5430419D17Rik. Rbpjl is a known regulator of ctrb, a gene associated with diabetes susceptibility. With 18-week in vivo cadmium exposure, we found more comprehensive changes in gene expression profile. Pathway enrichment analysis showed that these secondary changes were clustered to molecular mechanisms related to intracellular protein trafficking to the plasma membrane. In islet culture, cadmium ex vivo significantly induces the expression of Mt1, Sphk1, Nrcam, L3mbtl2, Rnf216 and Itpr1. Mt1 and Itpr1 are known to be involved in glucose homeostasis. Collectively, findings reported here revealed a complex cadmium-mediated effect on pancreatic islet gene expression at environmentally relevant cadmium exposure conditions, providing the basis for further studies into the pathophysiological processes arising from cadmium accumulation in pancreatic islets.
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Cloruro de Cadmio/toxicidad , Perfilación de la Expresión Génica , Islotes Pancreáticos/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Administración Oral , Animales , Cloruro de Cadmio/administración & dosificación , Cloruro de Cadmio/sangre , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Islotes Pancreáticos/metabolismo , Masculino , Ratones Endogámicos C57BL , RNA-Seq , Factores de Tiempo , Técnicas de Cultivo de TejidosRESUMEN
BACKGROUND: Current digital cell imaging systems perform peripheral blood smear (PBS) analysis in limited regions of the PBS and require the support of manual microscopy without achieving full digital microscopy. We report a multicenter study that validated the Scopio Labs X100 Full Field PBS, a novel digital imaging system that utilizes a full field view approach for cell recognition and classification, in a decision support system mode. METHODS: We analyzed 335 normal and 310 abnormal PBS from patients with various clinical conditions and compared the performance of Scopio's Full Field PBS as the test method, with manual PBS analysis as the reference method. Deming regression analysis was utilized for comparisons of WBC and platelet estimates. Measurements of WBC and platelet estimation accuracy along with the agreement on RBC morphology evaluation were performed. Reproducibility and repeatability (R&R) of the system were also evaluated. RESULTS: Scopio's Full Field PBS WBC accuracy was evaluated with an efficiency of 96.29%, sensitivity of 87.86%, and specificity of 97.62%. The agreement between the test and reference method for RBC morphology reached 99.77%, and the accuracy for platelet estimation resulted in an efficiency of 94.89%, sensitivity of 90.00%, and specificity of 96.28%, with successful R&R tests. The system enabled a comprehensive review of full field PBS as shown in representative samples. CONCLUSIONS: Scopio's Full Field PBS showed a high degree of correlation of all tested parameters with manual microscopy. The novel full field view of specimens facilitates the long-expected disengagement between the digital application and the manual microscope.
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Inteligencia Artificial , Células Sanguíneas/patología , Procesamiento de Imagen Asistido por Computador , Recuento de Células Sanguíneas/métodos , Células Sanguíneas/citología , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Microscopía/métodos , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVES: Research suggests nonoccupational post exposure prophylaxis (nPEP) is under prescribed for people seeking treatment within 72 h of human immunodeficiency virus (HIV) exposures in the emergency department (ED). This study is an assessment of ED prescribers' knowledge, attitudes and practices regarding administration of HIV nPEP. METHODS: This was an anonymous survey based on literature review and modified Delphi technique. We approached 153 ED participants at work over a 4-month period from 5 hospital-based and 2 freestanding EDs. There were 152 completed surveys: 80 attendings, 27 residents, and 44 physician assistants. RESULTS: The majority of those surveyed (133/149, 89.3%) believe it is their responsibility to provide HIV nPEP in the ED. Although 91% (138/151) and 87% (132/151) of participants are willing to prescribe nPEP for IV drug use and unprotected sex, respectively, only 40% (61/152) of participants felt they could confidently prescribe the appropriate regimen. Only 25% (37/151) of participants prescribed nPEP in the last year. Participants considered time (27%), connecting patients to follow-up (26%), and cost to patients (23%), as barriers to prescribing nPEP. CONCLUSIONS: This study identified perceived barriers to administration of nPEP and missed opportunities for HIV prevention in the ED. Although most ED prescribers were willing to prescribe nPEP and felt it is their responsibility to do so, the majority of prescribers were not confident in prescribing it. The most commonly cited barriers to prescribing nPEP were time and access to follow-up care.
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Servicio de Urgencia en Hospital , Infecciones por VIH/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Profilaxis Posexposición/métodos , Adulto , Técnica Delphi , Femenino , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
Kratom (Mitragyna speciosa, Korth) is a tree-like plant that is indigenous to Southeast Asia. Kratom leaf products have been used in traditional folk medicine for their unique combination of stimulant and opioid-like effects. Kratom is being increasingly used in the West for its reputed benefits in the treatment of pain, depression and opioid use disorder. Recently, the United States Food and Drug Administration and Centers for Disease Control have raised concerns regarding the contamination of some kratom products with toxic metals (Pb and Ni) and microbes such as Salmonella. To further explore this issue, eight different kratom products were legally purchased from various "head"/"smoke" shops in the Western Suburbs of Chicago and then tested for microbial burden, a panel of metals (Ni, Pb, Cr, As, Hg, Cd), and levels of the main psychoactive alkaloid mitragynine. All of the samples contained significant, but variable, levels of mitragynine (3.9-62.1 mg/g), indicating that the products were, in fact, derived from kratom. All but two of the samples tested positive for the presence of various microbes including bacteria and fungi. However, none of the samples tested positive for Salmonella. Seven products showed significant levels of Ni (0.73-7.4 µg/g), Pb (0.16-1.6 µg/g) and Cr (0.21-5.7 µg/g) while the other product was negative for metals. These data indicate that many kratom products contain variable levels of mitragynine and can contain significant levels of toxic metals and microbes. These findings highlight the need for more stringent standards for the production and sale of kratom products.
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Mitragyna , Alcaloides de Triptamina Secologanina , Chicago , Metales/análisis , Mitragyna/química , Hojas de la Planta , Alcaloides de Triptamina Secologanina/análisis , Estados UnidosRESUMEN
In a previously published report we detailed an in situ method to quantify cell death in the renal cortex by perfusing the cell membrane impermeable fluorochrome, ethidium homodimer in situ. The objective of the present study was to use this in situ viability assay to examine cell death following the administration of nephrotoxic drugs known to produce cell death and/or injury in specific segments of the nephron. Male Sprague/Dawley rats were treated with the following nephrotoxicants: Gentamicin, amphotericin-B, and indomethacin. Results of the in situ viability assay indicated that gentamicin and amphotericin-B treatment caused cell death localized in the kidney cortex and medulla, respectively. The urinary biomarker kidney injury molecule-1 (Kim-1) showed significant increases in both gentamicin (20 fold increase) and amphotericin-B-treated (9.2 fold increase) animals. Urinary alpha glutathione-S-transferase (GST) showed significant increases for gentamicin (6.2 fold increase) only and mu GST for amphotericin-B-treated (19.1 fold increase) animals only. These results show that this in situ viability assay provides a sensitive method to identify cell death in different regions of the kidney. Furthermore, urinary alpha GST and mu GST are specific for proximal and distal tubule injury, respectively; urinary Kim-1 demonstrated greater sensitivity to both proximal and distal tubule injury.
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Cadmium (Cd) is an anthropogenic as well as a naturally occurring toxicant associated with prediabetes and T2DM in humans and experimental models of Cd exposure. However, relatively few studies have examined the mechanism(s) of Cd-induced hyperglycemia. The purpose of this study was to examine the role of pancreatic islets in Cd-induced hyperglycemia. Male Sprague-Dawley rats were given daily subcutaneous doses of Cd at 0.6 mg/kg over 12 weeks. There was a resulting time-dependent increase in fasting blood glucose and altered insulin release in vitro. Islets isolated from control (saline-treated) and Cd-treated animals were incubated in low (0.5 mg/mL) or high (3 mg/mL) glucose conditions. Islets from 12 week Cd-treated animals had significantly less glucose-stimulated insulin release compared to islets from saline-treated control animals. The actual Cd content of isolated islets was 5 fold higher than the whole pancreas (endocrine + exocrine) and roughly 70% of that present in the renal cortex. Interestingly, islets isolated from Cd-treated animals and incubated in high glucose conditions contained significantly less Cd and zinc than those incubated in low glucose. These results show that within whole pancreatic tissue, Cd selectively accumulates in pancreatic islets and causes altered islet function that likely contributes to dysglycemia.
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Glucemia/análisis , Cadmio/análisis , Cadmio/toxicidad , Hiperglucemia/patología , Secreción de Insulina/efectos de los fármacos , Islotes Pancreáticos/patología , Animales , Hiperglucemia/inducido químicamente , Hiperglucemia/metabolismo , Islotes Pancreáticos/metabolismo , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVES: To design a questionnaire to evaluate and distinguish between cognitive and physical aspects of fatigue in different age groups of "nondiseased" people and guide appropriate prevention and interventions for the impact of frailty occurring in normative aging. STUDY DESIGN AND PARTICIPANTS: The Norfolk QOL-Fatigue (QOL-F) with items of cognitive and physical fatigue, anxiety, and depression from validated questionnaires including items from the Patient-Reported Outcomes Measure Information System (PROMIS) databank was developed. The preliminary QOL-F was administered to 409 healthy multiethnic local participants (30-80 years old) in 5 age groups. METHODS: The authors distilled the item pool using exploratory (EFA) and confirmatory factor analysis (CFA). EFA identified 5 latent groups as possible factors related to problems due to fatigue, subjective fatigue, reduced activities, impaired activities of daily living (ADL), and depression. RESULTS: CFA demonstrated good overall fit [χ2(172) = 1094.23, P < .001; Tucker-Lewis index = 0.978; root mean square error of approximation = 0.049] with factor loadings >0.617 and strong interfactor correlations (0.69-0.83), suggesting that fatigue in each domain is closely related to other domains and to the overall scale except for ADL. The 5-factor solution displayed good internal consistency (Cronbach α = 0.78-0.94). Total and domain scores were fairly equivalent in all age groups except for the 40 to 49-year-old group with better overall scores. In addition, 70 to 79-year-olds had better ADL scores. In item response analysis, factor scores in different age groups were similar, so age may not be a significant driver of fatigue scores. Fatigue scores were significantly higher in females than in males (P < .05). CONCLUSIONS AND CLINICAL IMPLICATIONS: The developed Norfolk QOL-F tool demonstrated fatigue as a perceived cognitive phenomenon rather than an objective physical measure, suggesting mandatory inclusion of cognitive as well as physical measures in the evaluation of people as they age. QOL-F is able to distinguish QOL-F domain scores unique to different age groups, proposing clinical benefits from physical, balance, and cognitive interventions tailored to impact frailty occurring in normative aging.
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Actividades Cotidianas , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Fatiga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Percepción , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
The understanding of cellular Cd2+ accumulation and toxicity is hampered by a lack of fluorescent indicators selective for intracellular free Cd2+ ([Cd2+]i). In this study, we used depolarized MIN6 mouse pancreatic beta cells as a model for evaluating [Cd2+]i detection with commercially available fluorescent probes, most of which have been traditionally used to visualize [Ca2+]i and [Zn2+]i. We trialed a panel of 12 probes including fura-2, FluoZin-3, Leadmium Green, Rhod-5N, indo-1, Fluo-5N, and others. We found that the [Zn2+]i probe FluoZin-3 and the traditional [Ca2+]i probe fura-2 responded most consistently and robustly to [Cd2+]i accumulation mediated by voltage-gated calcium channels. While selective detection of [Cd2+]i by fura-2 required the omission of Ca2+ from extracellular buffers, FluoZin-3 responded to [Cd2+]i similarly in the presence or absence of extracellular Ca2+. Furthermore, we showed that FluoZin-3 and fura-2 can be used together for simultaneous monitoring of [Ca2+]i and [Cd2+]i in the same cells. None of the other fluorophores tested were effective [Cd2+]i detectors in this model.
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Cadmio/análisis , Colorantes Fluorescentes/análisis , Fura-2/análisis , Células Secretoras de Insulina/química , Células Secretoras de Insulina/metabolismo , Compuestos Policíclicos/análisis , Animales , Cadmio/metabolismo , Línea Celular , Colorantes Fluorescentes/química , Fura-2/química , Espectrometría de Masas , Ratones , Microscopía Fluorescente , Compuestos Policíclicos/químicaRESUMEN
Cadmium (Cd) is an environmental toxicant that accumulates in bone and alters bone turnover and metabolism. Periodontal disease is characterized by tooth loss and tissue destruction, specifically, loss of supporting bone around the teeth. We have previously shown that Cd causes loss of dental alveolar (tooth supporting) bone in a rodent model of long-term Cd poisoning. The overall goal of this study was to determine the possible association between levels of Cd in alveolar bone and evidence of periodontal disease in human cadavers. The extent of Cd accumulation in human mandible samples was analyzed. Levels of Cd in mandibular alveolar bone were compared to those in basal bone as well as the renal cortex in samples obtained from the cadavers. Alveolar bone contained significantly higher levels of Cd when compared to basal bone (p < 0.01). Cd levels in mandibular bone were significantly higher in female compared to male cadavers (p < 0.05). The kidney cortex had greater than 15-fold higher Cd levels compared to mandible bone. Additional analyses showed a possible association between levels of Cd in basal bone and the presence of periodontal disease in cadavers from which the samples were obtained. This study shows that Cd accumulates to relatively high levels within alveolar bone as compared to basal bone in the mandible and thus may have a significant and direct effect in the progression of changes in bone associated with periodontal disease.
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Background HIV rates are persistently disproportionate among men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, now publicly funded in British Columbia. This study assessed PrEP-related attitudes, sexual behaviour and self-reported use before public funding. METHODS: Adult MSM were recruited from January to June 2017 through a local community-based organisation's PrEP campaign website (www.getpreped.ca). Participants self-completed an anonymous online questionnaire, and were stratified into three groups: (i) HIV-positive participants; (ii) HIV-negative participants not using PrEP; and (iii) HIV-negative participants using PrEP. Descriptive, bivariate and univariate regression analyses were conducted. RESULTS: Of 249 participants, 191 (77%) were HIV-negative not using PrEP, 41 (17%) were HIV-negative using PrEP and 17 (7%) were HIV-positive. Among PrEP users, 90% used PrEP daily and all reported having recommended medical follow-up care. Among HIV-negative, non-PrEP-users, 44% said they would reduce condom use if they used PrEP and 28% were uncomfortable asking their doctor for PrEP. Interest in PrEP among non-users was associated with higher objective risk scores (i.e. HIV Incidence Risk Index for MSM), higher self-perceived risk, greater perceived PrEP effectiveness, no prescription medications insurance, open or single relationship status (vs closed) and not always using condoms (vs always). Among HIV-positive participants, 53% agreed PrEP reduced stigma for people living with HIV. All study groups perceived a greater percentage of MSM on PrEP (10%, 15%, 18%) than in their own social networks (5%, 4%, 6%). CONCLUSIONS: PrEP health promotion must consider comprehensive PrEP education; accuracy of self-perceived HIV risk and PrEP social norms; and barriers to culturally safe primary care for MSM.
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Infecciones por VIH/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Adulto , Colombia Británica , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Cadmium is a toxic metal and common environmental contaminant. Chronic cadmium exposure results in kidney, bone, reproductive, and immune toxicity as well as cancer. Cadmium induces splenomegaly and affects the adaptive immune system, but specific effects vary depending on the dose, model, and endpoint. This study investigates the effects of subchronic, oral, and low-dose cadmium exposure (32 ppm cadmium chloride in drinking water for 10 weeks) on the rat immune system, focusing on T cell function. Cadmium-exposed animals demonstrated slight increases in the spleen-to-body weight ratios, and decreases in overall splenic cell numbers and markers of oxidative stress. The relative ratios of splenic cell populations remained similar, except for modest increases in regulatory T cells in the cadmium-exposed animals. Cadmium exposure also significantly increased the production of IFNγ, a pro-inflammatory cytokine, and IL-10, a cytokine produced by multiple T cell subsets that typically inhibits IFNγ expression, by activated T cells. The increase in IFNγ and IL-10 suggests that cadmium exposure may affect multiple T cell subsets. Collectively, this study suggests that subchronic, low-dose cadmium exposure impacts both immune cell function and cellularity, and may enhance inflammatory responses.