Subcapsular Sinus Macrophage Fragmentation and CD169+ Bleb Acquisition by Closely Associated IL-17-Committed Innate-Like Lymphocytes

Subcapsular sinus macrophages (SSMs) in lymph nodes are rapidly exposed to antigens arriving in afferent lymph and have a role in their capture and display to B cells. In tissue sections SSMs exhibit long cellular processes and express high amounts of CD169. Here, we show that many of the cells present in lymph node cell suspensions that stain for CD169 are not macrophages but lymphocytes that have acquired SSM-derived membrane blebs. The CD169 bleb+ lymphocytes are enriched for IL-17 committed IL-7RαhiCCR6+ T cells and NK cells. In addition, the CD169 staining detected on small numbers of CD11chi dendritic cells is frequently associated with membrane blebs. Counter intuitively the CD169 bleb+ lymphocytes are mostly CD4 and CD8 negative whereas many SSMs express CD4. In situ, many IL-7Rαhi cells are present at the subcapsular sinus and interfollicular regions and migrate in close association with CD169+ macrophages. These findings suggest SSMs undergo fragmentation during tissue preparation and release blebs that are acquired by closely associated cells. They also suggest an intimate crosstalk between SSMs and IL-17 committed innate-like lymphocytes that may help provide early protection of the lymph node against lymph-borne invaders

HIV vaccine trial safety and retention among 18-20 year olds in the HVTN 503/Phambili study support the inclusion of adolescents in future trials

Worldwide, many adolescents, especially women, acquire HIV before age 18. Yet to date, no HIV vaccine trials have enrolled adolescents. Reasons for excluding adolescents from these trials include regulations protecting vulnerable subjects and concerns regarding informed consent, social harms, adverse events, and loss to follow-up

Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study

Agnes Binagwaho and colleagues predict that circumcision of newborn boys would be effective and cost-saving as a long-term strategy to prevent HIV in Rwanda

Quantitative Microscopy of Hepatic Changes Induced by Phenethyl Isothiocyanate in Fischer-344 Rats Fed Either a Cereal-Based Diet or a Purified Diet

Hepatic changes induced by phenethyl isothiocyanate (PEITC) in the liver of rats were determined by quantitative microscopy. Groups of male Fischer-344 rats were fed either a standard, cereal-based diet (Wayne rodent meal) or a purified diet (AIN-76A) containing PEITC at concentrations of 0.75 and 6.0 mmol/kg for 13 wk. Severe hepatic lipidosis was observed in control rats fed the purified diet. Addition of PEITC to the purified diet significantly reduced lipid content in hepatocytes. In contrast, lipid content in the liver of the rats fed the cereal-based diet containing PEITC was greater than in control rats maintained on the same diet. In addition, dose-related reductions in hepatocyte, lipid droplet, peroxisome, and mitochondrial volumes were observed in PEITC-treated rats fed the cereal-based diet. These results indicate that PEITC exerts differential effects on the liver of rats fed either the cereal-based or purified diet.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68493/2/10.1177_019262339502300602.pd

Judging Time-to-Passage of looming sounds: evidence for the use of distance-based information

Perceptual judgments are an essential mechanism for our everyday interaction with other moving agents or events. For instance, estimation of the time remaining before an object contacts or passes us is essential to act upon or to avoid that object. Previous studies have demonstrated that participants use different cues to estimate the time to contact or the time to passage of approaching visual stimuli. Despite the considerable number of studies on the judgment of approaching auditory stimuli, not much is known about the cues that guide listeners’ performance in an auditory Time-to-Passage (TTP) task. The present study evaluates how accurately participants judge approaching white-noise stimuli in a TTP task that included variable occlusion periods (portion of the presentation time where the stimulus is not audible). Results showed that participants were able to accurately estimate TTP and their performance, in general, was weakly affected by occlusion periods. Moreover, we looked into the psychoacoustic variables provided by the stimuli and analysed how binaural cues related with the performance obtained in the psychophysical task. The binaural temporal difference seems to be the psychoacoustic cue guiding participants’ performance for lower amounts of occlusion, while the binaural loudness difference seems to be the cue guiding performance for higher amounts of occlusion. These results allowed us to explain the perceptual strategies used by participants in a TTP task (maintaining accuracy by shifting the informative cue for TTP estimation), and to demonstrate that the psychoacoustic cue guiding listeners’ performance changes according to the occlusion period.This study was supported by: Bial FoundationGrant 143/14 (https://www.bial.com/en/bial_foundation.11/11th_symposium.219/ fellows_preliminary_results.235/fellows_ preliminary_results.a569.html); FCT PTDC/EEAELC/112137/2009 (https://www.fct.pt/apoios/projectos/consulta/vglobal_projecto?idProjecto=112137&idElemConcurso=3628); and COMPETE: POCI-01-0145-FEDER-007043 and FCT – Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2013.info:eu-repo/semantics/publishedVersio

Tips and Traps: Lessons From Codesigning a Clinician E-Monitoring Tool for Computerized Cognitive Behavioral Therapy

Background: Computerized cognitive behavioral therapy (cCBT) is an acceptable and promising treatment modality for adolescents with mild-to-moderate depression. Many cCBT programs are standalone packages with no way for clinicians to monitor progress or outcomes. We sought to develop an electronic monitoring (e-monitoring) tool in consultation with clinicians and adolescents to allow clinicians to monitor mood, risk, and treatment adherence of adolescents completing a cCBT program called SPARX (Smart, Positive, Active, Realistic, X-factor thoughts). Objective: The objectives of our study were as follows: (1) assess clinicians’ and adolescents’ views on using an e-monitoring tool and to use this information to help shape the development of the tool and (2) assess clinician experiences with a fully developed version of the tool that was implemented in their clinical service. Methods: A descriptive qualitative study using semi-structured focus groups was conducted in New Zealand. In total, 7 focus groups included clinicians (n=50) who worked in primary care, and 3 separate groups included adolescents (n=29). Clinicians were general practitioners (GPs), school guidance counselors, clinical psychologists, youth workers, and nurses. Adolescents were recruited from health services and a high school. Focus groups were run to enable feedback at 3 phases that corresponded to the consultation, development, and post-implementation stages. Thematic analysis was applied to transcribed responses. Results: Focus groups during the consultation and development phases revealed the need for a simple e-monitoring registration process with guides for end users. Common concerns were raised in relation to clinical burden, monitoring risk (and effects on the therapeutic relationship), alongside confidentiality or privacy and technical considerations. Adolescents did not want to use their social media login credentials for e-monitoring, as they valued their privacy. However, adolescents did want information on seeking help, and personalized monitoring and communication arrangements. Post-implementation, clinicians who had used the tool in practice revealed no adverse impact on the therapeutic relationship, and adolescents were not concerned about being e-monitored. Clinicians did need additional time to monitor adolescents, and the e-monitoring tool was used in a different way than was originally anticipated. Also, it was suggested that the registration process could be further streamlined and integrated with existing clinical data management systems, and the use of clinician alerts could be expanded beyond the scope of simply flagging adolescents of concern. Conclusions: An e-monitoring tool was developed in consultation with clinicians and adolescents. However, the study revealed the complexity of implementing the tool in clinical practice. Of salience were privacy, parallel monitoring systems, integration with existing electronic medical record systems, customization of the e-monitor, and pre-agreed monitoring arrangements between clinicians and adolescents

Circumcision for prevention against HIV: marked seasonal variation in demand and potential public sector readiness in Soweto, South Africa

The public sector delivery of male circumcision in the only public sector hospital in Soweto, South Africa was examined to gauge local capacity to deliver this procedure as an intervention for prevention of HIV acquisition. During the period from July 1998 to March 2006, approximately 360 procedures were performed per annum. Striking seasonal variations and the relatively few procedures performed may create challenges for program planning, if male circumcision is increased to a level required to have an impact on the incidence of HIV among this population

Five-Year Longitudinal Assessment of the Downstream Impact on Schistosomiasis Transmission following Closure of the Three Gorges Dam

Schistosomiasis, caused by Schistosoma japonicum, is a significant parasitic disease and public health problem in China. How the parasite is transmitted there can be categorized into four distinct modes (modes I–IV) and it is predicted that the Three Gorges Dam, recently completed, will affect the way schistosomiasis is spread in these modes. We monitored transmission for a 5-year period (2002–2006) in eight villages, representative of the three modes (I–III) below the dam across four provinces (Hunan, Jiangxi, Hubei and Anhui) to determine whether there was any immediate impact of the dam on schistosomiasis spread. Human schistosomiasis incidence declined considerably within individual villages and each mode, and the yearly odds ratios (adjusted) for infection risk showed significant downward trends in all three modes over the follow-up period. The decreased human S. japonicum incidence recorded across transmission modes I–III was probably attributable to annual human and bovine praziquantel drug treatment. If an increase in schistosome transmission had occurred as a result of the dam, it would be of negligible size compared with this treatment-induced decline. There had thus been virtually no immediate impact of the TGD on schistosomiasis transmission downstream of the dam over the 5-year surveillance period

Routine versus needs-based MRI in patients with prolonged low back pain: a comparison of duration of treatment, number of clinical contacts and referrals to surgery

<p>Abstract</p> <p>Background</p> <p>The routine use of radiology is normally discouraged in patients with low back pain (LBP). Magnetic Resonance Imaging (MRI) provides clinicians and patients with detailed knowledge of spinal structures and has no known physical side effects. It is possible that insight into the pathological changes in LBP patients could affect patient management. However, to our knowledge, this has never been tested. Until June 2006, all patients at our specialised out-patient public clinic were referred for MRI on the basis of clinical indications, economic constraints, and availability of MRI (the "needs-based MRI" group). As a new approach, we now refer all patients who meet certain criteria for routine up-front MRI before the clinical examination (the "routine MRI" group).</p> <p>Objectives</p> <p>The aims of this study were to investigate if these two MRI approaches resulted in differences in: (1) duration of treatment, (2) number of contacts with clinicians, and (3) referral for surgery.</p> <p>Design</p> <p>Comparison of two retrospective clinical cohorts.</p> <p>Method</p> <p>Files were retrieved from consecutive patients in both groups. Criteria for referral were: (1) LBP or leg pain of at least 3 on an 11-point Numeric Rating Scale, (2) duration of present symptoms from 2 to12 months and (3) age above 18 years. A comparison was made between the "needs-based MRI" and "routine MRI" groups on the outcomes of duration of treatment and use of resources.</p> <p>Results</p> <p>In all, 169 "needs-based MRI" and 208 "routine MRI" patient files were identified. The two groups were similar in age, sex, and severity of LBP. However, the median duration of treatment for the "needs-based MRI" group was 160 versus 115 days in the "routine MRI" group (p = 0.0001). The median number of contacts with clinicians for the "needs-based MRI" group was 4 versus 3 for the "routine MRI" group (p = 0.003). There was no difference between the two approaches in frequency of referral for back surgery (p = 0.81). When the direct clinical costs were compared, the "routine MRI" group was less costly but only by €11.</p> <p>Conclusion</p> <p>In our clinic, the management strategy of routinely performing an up-front MRI at the start of treatment did reduce the duration of treatment and number of contacts with clinicians, and did not increase the rate of referral for back surgery. Also, the direct costs were not increased.</p