Adverse health outcomes among people who inject drugs who engaged in recent sex work: findings from a national survey.

OBJECTIVES: This study explores trends in sex work among people who inject drugs (PWID) by gender and the relationship between sex work and adverse health outcomes including overdose, injection-site, and blood-borne virus (BBV) infections. STUDY DESIGN: The Unlinked Anonymous Monitoring Survey of PWID is an annual cross-sectional survey that monitors BBV prevalence and behaviours, including transactional sex, among PWID recruited through specialist services in England, Wales, and Northern Ireland. METHODS: Trends in sex work among PWID (2011-2021) were described. Data were analysed to assess differences between PWID who engaged in sex work in the past year (sex workers [SWs]) and those who did not (non-SWs) by gender (Pearson Chi2 tests) (2018-2021). Associations between sex work in the past year and adverse health outcomes were investigated using logistic regression. RESULTS: Between 2011 and 2021, sex work among PWID remained stable, with 31% of women and 6.3% of men who inject, reporting having ever engaged in sex work, and 14% of women and 2.2% of men engaging in sex work in the past year. Between 2018 and 2021, SWs had greater odds of reporting symptoms of an injection-site infection (adjusted odds ratio (aOR): 1.68 [95% confidence interval {CI}: 1.31-2.16], P < 0.001) and reporting overdose (aOR: 2.21 [CI: 1.74-2.80], P < 0.001) than non-SWs had in the past year. Among men, SWs had 243% greater odds of having HIV than non-SWs (aOR: 3.43 [CI: 1.03-11.33], P = 0.043). CONCLUSIONS: Our findings highlight disproportionate vulnerability and intersection of overlapping risk factors experienced by PWID SWs and a need for tailored interventions which are inclusive and low-threshold.

Salmonella enterica Serovar Typhimurium Travels to Mesenteric Lymph Nodes Both with Host Cells and Autonomously.

Salmonella infection is a globally important cause of gastroenteritis and systemic disease and is a useful tool to study immune responses in the intestine. Although mechanisms leading to immune responses against Salmonella have been extensively studied, questions remain about how bacteria travel from the intestinal mucosa to the mesenteric lymph nodes (MLN), a key site for Ag presentation. In this study, we used a mouse model of infection with Salmonella enterica serovar Typhimurium (STM) to identify changes in intestinal immune cells induced during early infection. We then used fluorescently labeled STM to identify interactions with immune cells from the site of infection through migration in lymph to the MLN. We show that viable STM can be carried in the lymph by any subset of migrating dendritic cells but not by macrophages. Moreover, approximately half of the STM in lymph are not associated with cells at all and travel autonomously. Within the MLN, STM associates with dendritic cells and B cells but predominantly with MLN-resident macrophages. In conclusion, we describe the routes used by STM to spread systemically in the period immediately postinfection. This deeper understanding of the infection process could open new avenues for controlling it.

Music for Wellness in rehabilitation patients: programme description and evaluation results.

OBJECTIVE: The evaluation of real-world, hospital-based, arts programmes is important for quality assurance, to increase knowledge of successful practice and awareness of effective arts-health collaborations. The objective of this study was to describe the Music for Wellness programme and evaluation at St John of God Frankston Rehabilitation Hospital, Australia. STUDY DESIGN: An impact evaluation and quasi-experimental pre-post study was conducted. METHODS: The Music for Wellness programme for rehabilitation patients ran on a weekly basis for 18 weeks (i.e., 18 stand-alone workshops). Evaluation feedback was collected from patients and hospital staff/visitors. The primary outcome measures were pre-post workshop changes in patients' mood, measured via a 'faces' visual analogue scale; and pain, measured via a numerical rating scale. Linear mixed models and growth curve analyses were performed. Evaluation questions about mental well-being, pain reduction, musical skill attainment and the hospital environment were also asked and, a descriptive analysis was conducted. RESULTS: Between the baseline, preworkshop and postworkshop time points, a significant increase in rehabilitation patients' mood and decrease in self-reported pain were found. Changes were consistent over time. The patients and hospital staff/visitors agreed the programme enhanced the hospital environment and music skills, resulted in positive benefits (e.g., relaxation, opportunity to socialise) and should be continued. CONCLUSION: This study provides valuable information about a low-cost, non-pharmacological programme that successfully enhanced the hospital environment and supported patients' well-being in a rehabilitation setting.

[Concerns about child´s surgery. Are there differences if you belong to health sector?] / La preocupación ante la cirugía de un hijo. ¿Hay diferencias si perteneces al sector sanitario?

INTRODUCTION: A surgical intervention is a stress situation for every human being. Parents of children who undergo scheduled surgeries have some degree of anxiety about them. OBJECTIVE: To identify the main paternal concerns regarding surgery. Assess the influence of working in health (nurses, auxiliary staff and doctors) to underestimate, magnify or mislead the real concerns. MATERIAL AND METHOD: A comparative cross-sectional study was conducted between two populations divided by their relationship with the hospital setting that completed a questionnaire with 35 items. 138 questionnaires were collected and analyzed. RESULTS: Differences are observed regarding the perception we have, as hospital staff, of the levels, relationships and types of concerns that we believe parents present before their child's surgery regarding the true perceptions that these parents present. CONCLUSION: The present study shows that, although the hospital staff has experience in the management of pediatric patients and their family environment, the habituation to the hospital environment can generate small distortions in terms of the levels and groupings of the different concerns present before the hospital surgery of a child, having to take it into account to offer the best care work.

INTRODUCCION: Una intervención quirúrgica es una situación de estrés para todo ser humano. Los padres de niños que se someten a cirugías programadas presentan cierto grado de ansiedad con respecto a las mismas. OBJETIVO: El objetivo del presente estudio es identificar las principales preocupaciones paternas frente a la cirugía y valorar si la pertenencia laboral al mundo sanitario (enfermeros, personal auxiliar y médicos, principalmente) supone infravalorar, magnificar o equivocar dichas preocupaciones reales. MATERIAL Y METODOS: Se realizó un estudio transversal comparativo entre dos poblaciones divididas por su relación o no con el ámbito hospitalario que cumplimentaron un cuestionario con 37 ítems. Se recogieron y analizaron 138 cuestionarios. RESULTADOS: Se observan diferencias en cuanto a la percepción que tenemos, nosotros, como personal hospitalario, de los niveles, de las relaciones y los tipos de preocupaciones que creemos presentan los padres ante la cirugía de su hijo respecto a las verdaderas percepciones que presentan estos padres sin las vivencias diarias de una persona que trabaja en el mundo hospitalario. en dos ML al suspender el tratamiento. Tres pacientes presentaron hipertransaminasemia e hipercolesterolemia, sin precisar tratamiento médico. CONCLUSIONES: El presente estudio pone de manifiesto que, aunque el personal hospitalario tenga la experiencia sobre el manejo de pacientes pediátricos y su entorno familiar y, a pesar incluso, de poder tener hijos propios a su cargo, parece que la habituación a dicho ambiente hospitalario puede generar pequeñas distorsiones en cuanto a los niveles reales y a las agrupaciones de las distintas preocupaciones presentes ante la cirugía de un hijo. Esto debería tenerse en cuenta para ofrecer la mejor labor asistencial y mejorar el nivel de ansiedad que genera una intervención quirúrgica en el entorno familiar del paciente pediátrico.

Colorectal cancer: the facts in the case of the microbiota.

The importance of the microbiota in the development of colorectal cancer (CRC) is increasingly evident, but identifying specific microbial features that influence CRC initiation and progression remains a central task for investigators. Studies determining the microbial mechanisms that directly contribute to CRC development or progression are revealing bacterial factors such as toxins that contribute to colorectal carcinogenesis. However, even when investigators have identified bacteria that express toxins, questions remain about the host determinants of a toxin's cancer-potentiating effects. For other cancer-correlating bacteria that lack toxins, the challenge is to define cancer-relevant virulence factors. Herein, we evaluate three CRC-correlating bacteria, colibactin-producing Escherichia coli, enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum, for their virulence features relevant to CRC. We also consider the beneficial bioactivity of gut microbes by highlighting a microbial metabolite that may enhance CRC antitumor immunity. In doing so, we aim to elucidate unique and shared mechanisms underlying the microbiota's contributions to CRC and to accelerate investigation from target validation to CRC therapeutic discovery.

Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression.

The colorectal cancer (CRC)-associated microbiota creates a pro-tumorigenic intestinal milieu and shapes immune responses within the tumor microenvironment. However, how oncomicrobes - like Fusobacterium nucleatum, found in the oral cavity and associated with CRC tissues- affect these distinct aspects of tumorigenesis is difficult to parse. Herein, we found that neonatal inoculation of ApcMin/+ mice with F. nucleatum strain Fn7-1 circumvents technical barriers preventing its intestinal colonization, drives colonic Il17a expression prior to tumor formation, and potentiates intestinal tumorigenesis. Using gnotobiotic mice colonized with a minimal complexity microbiota (the altered Schaedler's flora), we observed that intestinal Fn7-1 colonization increases colonic Th17 cell frequency and their IL-17A and IL-17F expression, along with a concurrent increase in colonic lamina propria Il23p19 expression. As Fn7-1 stably colonizes the intestinal tract in our models, we posited that microbial metabolites, specifically short-chain fatty acids (SCFA) that F. nucleatum abundantly produces in culture and, as we demonstrate, in the intestinal tract, might mediate part of its immunomodulatory effects in vivo. Supporting this hypothesis, we found that Fn7-1 did not alter RORγt+ CD4+T cell frequency in the absence of the SCFA receptor FFAR2. Taken together, our work suggests that F. nucleatum influences intestinal immunity by shaping Th17 responses in an FFAR2-dependent manner, although further studies are necessary to clarify the precise and multifaceted roles of FFAR2. The potential to increase intestinal Th17 responses is shared by another oncomicrobe, enterotoxigenic Bacteroides fragilis, highlighting a conserved pathway that could potentially be targeted to slow oncomicrobe-mediated CRC.

The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease.

To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs. We used these protocols to purify and characterize colonic macrophages from colonic tissue from patients with Crohn's disease (CD), ulcerative colitis (UC), or non-inflamed controls, in a cross-sectional study. We identify macrophage populations (CD45+CD64+ HLA-DR+) and describe two distinct subsets, differentiated by their expression of the mannose receptor, CD206. CD206+ macrophages expressed markers consistent with a mature phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of TREM1. CD206- macrophages appear to be less mature, with features more similar to their monocytic precursors. We identified and purified macrophage populations from human colon. These appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature, they acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD.

Regulatory T cells control the dynamic and site-specific polarization of total CD4 T cells following Salmonella infection.

FoxP3+ regulatory T cells (Tregs) control inflammation and maintain mucosal homeostasis, but their functions during infection are poorly understood. Th1, Th2, and Th17 cells can be identified by master transcription factors (TFs) T-bet, GATA3, and RORγT; Tregs also express these TFs. While T-bet+ Tregs can selectively suppress Th1 cells, it is unclear whether distinct Treg populations can alter Th bias. To address this, we used Salmonella enterica serotype Typhimurium to induce nonlethal colitis. Following infection, we observed an early colonic Th17 response within total CD4 T cells, followed by a Th1 bias. The early Th17 response, which contains both Salmonella-specific and non-Salmonella-specific cells, parallels an increase in T-bet+ Tregs. Later, Th1 cells and RORγT+ Tregs dominate. This reciprocal dynamic may indicate that Tregs selectively suppress Th cells, shaping the immune response. Treg depletion 1-2 days post-infection shifted the early Th17 response to a Th1 bias; however, Treg depletion 6-7 days post-infection abrogated the Th1 bias. Thus, Tregs are necessary for the early Th17 response, and for a maximal Th1 response later. These data show that Tregs shape the overall tissue CD4 T cell response and highlight the potential for subpopulations of Tregs to be used in targeted therapeutic approaches.

Observations of strain accumulation across the san andreas fault near palmdale, california, with a two-color geodimeter.

Two-color laser ranging measurements during a 15-month period over a geodetic network spanning the San Andreas fault near Palmdale, California, indicate that the crust expands and contracts aseismically in episodes as short as 2 weeks. Shear strain parallel to the fault has accumulated monotonically since November 1980, but at a variable rate. Improvements in measurement precision and temporal resolution over those of previous geodetic studies near Palmdale have resulted in the definition of a time history of crustal deformation that is much more complex than formerly realized.

River channel conveyance capacity adjusts to modes of climate variability.

River networks are typically treated as conduits of fixed discharge conveyance capacity in flood models and engineering design, despite knowledge that alluvial channel networks adjust their geometry, conveyance, planform, extent and drainage density over time in response to shifts in the magnitude and frequency of streamflows and sediment supply. Consistent relationships between modes of climate variability conducive to wetter-/drier-than-average conditions and changes in channel conveyance have never been established, hindering geomorphological prediction over interannual to multidecadal timescales. This paper explores the relationship between river channel conveyance/geometry and three modes of climate variability (the El Niño-Southern Oscillation, Atlantic Multidecadal Oscillation, and Arctic Oscillation) using two-, five- and ten-year medians of channel measurements, streamflow, precipitation and climate indices over seven decades in 67 United States rivers. We find that in two thirds of these rivers, channel capacity undergoes coherent phases of expansion/contraction in response to shifts in catchment precipitation and streamflow, driven by climate modes with different periodicities. Understanding the sensitivity of channel conveyance to climate modes would enable better river management, engineering design, and flood predictability over interannual to multidecadal timescales.

Vertebroplasty and Kyphoplasty for Osteoporotic Vertebral Fractures: What Are the Latest Data?

Osteoporotic vertebral compression fractures frequently result in significant morbidity and health care resource use. For patients with severe and disabling pain, vertebral augmentation (vertebroplasty and kyphoplasty) is often considered. Although vertebroplasty was introduced >30 years ago, there are conflicting opinions regarding the role of these procedures in the treatment of osteoporotic vertebral compression fractures. This review article updates clinicians on the published prospective randomized controlled data, including the most recent positive trials that followed initial negative trials in 2009. Analysis of multiple national claim datasets has also provided further insight into the utility of these procedures. Finally, we considered the recent recommendations of national organizations and medical societies that advise on the use of vertebral augmentation procedures for osteoporotic vertebral compression fractures.

Cyclosporin A reverses vincristine and daunorubicin resistance in acute lymphatic leukemia in vitro.

The development of drug resistance by tumor cells is a major obstacle to the cure of human malignancy. Cyclosporin A (CsA) completely reverses primary resistance to vincristine and cross resistance to daunorubicin in a pleiotropic drug-resistant subline of human T cell acute lymphatic leukemia. This subline is over 50-fold resistant to vincristine and fivefold resistant to daunorubicin. CsA has little effect on vincristine or daunorubicin activity in drug-sensitive parental leukemia and corrects daunorubicin resistance without altering cellular daunorubicin accumulation.

Verapamil restoration of daunorubicin responsiveness in daunorubicin-resistant Ehrlich ascites carcinoma.

We have studied the influence of verapamil hydrochloride on the in vitro and in vivo effects of daunorubicin in Ehrlich ascites carcinoma. Daunorubicin-sensitive tumor was rendered resistant to daunorubicin by the continuous treatment of sequential generations of tumor-bearing BALB/c mice. The ability of daunorubicin to inhibit [(3)H]uridine and [(3)H]thymidine incorporation and the effect of daunorubicin on the mean survival time of host animals bearing daunorubicin-sensitive and daunorubicin-resistant Ehrlich ascites carcinoma were compared. The addition of verapamil to daunorubicin in vitro reduced the concentration of daunorubicin required to inhibit 50% of DNA and RNA synthesis in the daunorubicin-resistant tumor to that required in the daunorubicin-sensitive tumor, from 6 and 4.4 mug/ml to 1.5 and 1.3 mug/ml, respectively. Verapamil also restored drug sensitivity to daunorubicin-resistant Ehrlich ascites carcinoma in vivo. The 21.7+/-0.7 d mean survival time (MST) of BALB/c mice bearing daunorubicin-resistant tumor treated with daunorubicin alone rose to 44.0+/-0.7 d when the same tumor was treated with verapamil and daunorubicin, P < 0.001. This in vivo effect is specific for daunorubicin-resistant Ehrlich ascites carcinoma, since there is no alteration in MST of BALB/c mice bearing daunorubicin-sensitive or daunorubicin-resistant tumor when they are treated with verapamil alone or when BALB/c mice bearing daunorubicin-sensitive tumor are treated with daunorubicin and verapamil.

Evidence of cardiac autonomic neuropathy in dogs with diabetes mellitus.

The NeuroScope, a specific and sensitive indicator of cardiac vagal tone, was used to look for differences in autonomic tone between 25 dogs with naturally occurring diabetes mellitus and 23 healthy control dogs, to determine whether there was any correlation between the dogs' cardiac vagal tone, the duration of diabetes and the adequacy of glycaemic control. The cardiac index of parasympathetic activity (cipa) was determined for each dog over a period of 2600 heartbeats. The mean, median and modal cipa values were significantly lower in the diabetic dogs than in the healthy dogs. There was no significant relationship between the cipa values and the duration of disease or the adequacy of recent glycaemic control in the diabetic dogs, but there was a significant inverse relationship between the cipa values and the bodyweight of the diabetic dogs that was not evident in the normal dogs. The conclusions were based on a 500-heartbeat interval selected from the 2600 heartbeats recorded.

Changes in the glomerular filtration rate of 27 cats with hyperthyroidism after treatment with radioactive iodine.

Hyperthyroidism is a common endocrinopathy of older cats and is associated with an increased glomerular filtration rate (gfr). Renal dysfunction is also common in older cats and may develop after they have been treated for hyperthyroidism. This paper describes the changes in the gfr of 27 hyperthyroid cats in the six months after their treatment with radioactive iodine ((131)I), and evaluates whether any commonly measured pretreatment parameters (serum biochemistry, systolic blood pressure, urine specific gravity) could predict a clinically significant decline in renal function. The gfr of all the cats had decreased one month after treatment, and the mean gfr was significantly lower. There was no further significant change in gfr between one and six months. The only independent variable associated with the final gfr was the pretreatment plasma glucose concentration (P=0.003).

Cyclosporin A and verapamil enhancement of daunorubicin-produced nucleolar protein B23 translocation in daunorubicin-resistant and -sensitive human and murine tumor cells.

It has recently been shown that anthracycline antibiotic-resistant tumor cells are less responsive to daunorubicin-stimulated B23 nucleolar phosphoprotein translocation than drug-sensitive cells. Since cyclosporin A and verapamil reverse primary acquired and secondary cross-resistance to daunorubicin, we investigated the effect of these agents on nucleolar B23 translocation in sensitive and resistant tumors. We compared modified to baseline B23 phosphoprotein distribution between predominantly nucleolar, mixed nucleolar-nuclear, or nuclear immunofluorescence using a monoclonal anti-B23 antibody in parental drug-sensitive and multidrug-resistant acute lymphatic leukemia and in daunorubicin-sensitive and -resistant murine hepatoma. Our experiments show that cyclosporin A and verapamil alone have no effect on B23 phosphoprotein translocation, but that the addition of either agent to sensitive parental or resistant tumor sublines markedly enhances daunorubicin-stimulated translocation. This effect correlates with the correction of impaired daunorubicin inhibition of RNA synthesis by cyclosporin A and verapamil in the resistant sublines. Our observations suggest that nucleolar B23 phosphoprotein is an important site in the modulation of anthracycline antibiotic antitumor activity.

Effect of antineoplastic agents on gamma-interferon production in human peripheral blood mononuclear cells.

Since gamma-interferon (IFN-gamma) is a potent immunomodulator and patients receiving certain antineoplastic agents are at risk of unusual infections, we have determined the effect of certain antineoplastic agents on IFN-gamma production. Induction of peripheral blood mononuclear cells from normal donors in the presence and absence of various antineoplastic agents was achieved using phytohemagglutinin (8 micrograms/ml). Supernatants were then separated by centrifugation, dialyzed, and assayed for interferon. Cell viability was always greater than 85% with or without the presence of drugs. Hydrocortisone was found to eliminate IFN-gamma production if added within 24 hr after the phytohemagglutinin. The suppression of IFN-gamma production occurred with hydrocortisone concentrations as low as 0.65 microgram/ml, was associated with a diminished proliferative response to the lectin, and occurred with other interferon inducers including staphylococcal enterotoxin A. Adriamycin (0.4 microgram/ml) and vincristine (0.08 microgram/ml) also diminished IFN-gamma production, but only if the peripheral blood mononuclear cells were pretreated with the drugs. Methotrexate, 5-fluorouracil, and 6-mercaptopurine failed to influence the yield of IFN-gamma. These results are significantly different from experiments previously reported using alpha- and beta-interferons and suggest an important mechanism by which these drugs can produce immunosuppression.

Enhancement by cyclosporin A of daunorubicin efficacy in Ehrlich ascites carcinoma and murine hepatoma 129.

Cyclosporin A abrogates pleiotropic drug resistance in certain experimental tumors. Its impact on drug-sensitive tumors has not been investigated. Our studies show that in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 cyclosporin A enhances daunorubicin inhibition of DNA synthesis in vitro and prolongs survival of host mice in vivo. Of particular interest is that cyclosporin A converts ineffective daunorubicin regimens into those which result in prolongation of host mice survival. Other agents known to reverse pleiotropic drug resistance are reported to exert their effects by increasing intracellular drug accumulation. In contrast, our studies of drug transport in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 show that cyclosporin A causes minimal enhancement of [3H]daunorubicin uptake without inhibition of [3H]daunorubicin efflux in both the presence and absence of interrupted active daunorubicin efflux. This suggests that the mechanism of action of daunorubicin enhancement by cyclosporin A in drug-sensitive tumors is not simply the result of increased intracellular daunorubicin accumulation. In vivo dosages of cyclosporin A in the current study are comparable to those which can be used with reasonable safety in humans. We conclude that cyclosporin A may be useful in the potentiation of anthracycline antibiotic therapy directed against drug-sensitive as well as drug-resistant tumors.

TICI and Age: What's the Score?

BACKGROUND AND PURPOSE: Previous studies have suggested that advanced age predicts worse outcome following mechanical thrombectomy. We assessed outcomes from 2 recent large prospective studies to determine the association among TICI, age, and outcome. MATERIALS AND METHODS: Data from the Solitaire FR Thrombectomy for Acute Revascularization (STAR) trial, an international multicenter prospective single-arm thrombectomy study and the Solitaire arm of the Solitaire FR With the Intention For Thrombectomy (SWIFT) trial were pooled. TICI was determined by core laboratory review. Good outcome was defined as an mRS score of 0-2 at 90 days. We analyzed the association among clinical outcome, successful-versus-unsuccessful reperfusion (TICI 2b-3 versus TICI 0-2a), and age (dichotomized across the median). RESULTS: Two hundred sixty-nine of 291 patients treated with Solitaire in the STAR and SWIFT data bases for whom TICI and 90-day outcome data were available were included. The median age was 70 years (interquartile range, 60-76 years) with an age range of 25-88 years. The mean age of patients 70 years of age or younger was 59 years, and it was 77 years for patients older than 70 years. There was no significant difference between baseline NIHSS scores or procedure time metrics. Hemorrhage and device-related complications were more common in the younger age group but did not reach statistical significance. In absolute terms, the rate of good outcome was higher in the younger population (64% versus 44%, P < .001). However, the magnitude of benefit from successful reperfusion was higher in the 70 years of age and older group (OR, 4.82; 95% CI, 1.32-17.63 versus OR 7.32; 95% CI, 1.73-30.99). CONCLUSIONS: Successful reperfusion is the strongest predictor of good outcome following mechanical thrombectomy, and the magnitude of benefit is highest in the patient population older than 70 years of age.