OMIP-103: A 35-marker imaging mass cytometry panel for the co-detection of HIV and immune cell populations in human formalin fixed paraffin embedded intestinal tissue.

We introduce a 35-marker imaging mass cytometry (IMC) panel for a detailed examination of immune cell populations and HIV RNA in formalin fixed paraffin embedded (FFPE) human intestinal tissue. The panel has broad cell type coverage and particularly excels in delineating subsets of mononuclear phagocytes and T cells. Markers for key tissue structures are included, enabling identification of epithelium, blood vessels, lymphatics, and musculature. The described method for HIV RNA detection can be generalized to other low abundance RNA targets, whether endogenous or pathogen derived. As such, the panel presented here is useful for high parameter spatial mapping of intestinal immune cells and their interactions with pathogens such as HIV.

Spatial analysis for highly multiplexed imaging data to identify tissue microenvironments.

Highly multiplexed in situ imaging cytometry assays have made it possible to study the spatial organization of numerous cell types simultaneously. We have addressed the challenge of quantifying complex multi-cellular relationships by proposing a statistical method which clusters local indicators of spatial association. Our approach successfully identifies distinct tissue architectures in datasets generated from three state-of-the-art high-parameter assays demonstrating its value in summarizing the information-rich data generated from these technologies.

An in situ analysis pipeline for initial host-pathogen interactions reveals signatures of human colorectal HIV transmission.

The initial immune response to HIV determines transmission. However, due to technical limitations we still do not have a comparative map of early mucosal transmission events. By combining RNAscope, cyclic immunofluorescence, and image analysis tools, we quantify HIV transmission signatures in intact human colorectal explants within 2 h of topical exposure. We map HIV enrichment to mucosal dendritic cells (DCs) and submucosal macrophages, but not CD4+ T cells, the primary targets of downstream infection. HIV+ DCs accumulate near and within lymphoid aggregates, which act as early sanctuaries of high viral titers while facilitating HIV passage to the submucosa. Finally, HIV entry induces recruitment and clustering of target cells, facilitating DC- and macrophage-mediated HIV transfer and enhanced infection of CD4+ T cells. These data demonstrate a rapid response to HIV structured to maximize the likelihood of mucosal infection and provide a framework for in situ studies of host-pathogen interactions and immune-mediated pathologies.

spicyR: spatial analysis of in situ cytometry data in R.

MOTIVATION: High parameter histological techniques have allowed for the identification of a variety of distinct cell types within an image, providing a comprehensive overview of the tissue environment. This allows the complex cellular architecture and environment of diseased tissue to be explored. While spatial analysis techniques have revealed how cell-cell interactions are important within the disease pathology, there remains a gap in exploring changes in these interactions within the disease process. Specifically, there are currently few established methods for performing inference on cell-type co-localization changes across images, hindering an understanding of how cellular environments change with a disease pathology. RESULTS: We have developed the spicyR R package to perform inference on changes in the spatial co-localization of types across groups of images. Application to simulated data demonstrates a high sensitivity and specificity. We the utility of spicyR by applying it to a type 1 diabetes imaging mass cytometry dataset, revealing changes in cellular associations that were relevant to the disease progression. Ultimately, spicyR allows changes in cellular environments to be explored under different pathologies or disease states. AVAILABILITY AND IMPLEMENTATION: R package is freely available at http://bioconductor.org/packages/release/bioc/html/spicyR.html and shiny app implementation at http://shiny.maths.usyd.edu.au/spicyR/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Impact on mental healthcare after collaboration between primary healthcare and mental health services]. / Impacto en la asistencia en salud mental tras la colaboración entre atención primaria y salud mental.

INTRODUCTION: The primary care physician is the professional with whom the psychiatric patient has contact first and most frequently. For this reason, a good coordination between the Primary Healthcare (PHC) and Mental Health (MH) services is essential to provide the best care to patients and at the same time optimise the limited resources of this service. The aim of this work is to determine whether the collaboration between PHC and MH results in a more efficient use of the limited resources in MH. METHODOLOGY: An observational, retrospective, mirror study was carried out with a total sample of 135 patients over 16 years old referred for the first time from PHC to Psychiatry. The results during the first 6 months of the collaboration between PHC and MH (POST Group) are compared with those of the 6 months prior to the intervention (PRE Group). RESULTS: After collaboration meetings, the percentage of patients who are discharged by the psychiatrist after the first visit decreases (32.2% vs. 16%) and the percentage of follow-up by psychiatry and psychology increases. Furthermore, the percentage of patients who do not attend the first visit decreases (23.3% vs. 13.7%). CONCLUSIONS: The data suggest that the collaboration between PHC and MH improves the effectiveness and functioning of MH services.

Efficacy of vitamin D in the treatment of depression: a systematic review and meta-analysis.

Vitamin D is a fat-soluble vitamin that performs multiple functions in the body. In addition to regulating calcium and phosphate levels in the body and contributing to bone mineralization, it participates in various brain and neurocognitive processes. In fact, the deficiency of this vitamin has also been linked to various psychiatric disorders, including depression.

AFid: a tool for automated identification and exclusion of autofluorescent objects from microscopy images.

MOTIVATION: Autofluorescence is a long-standing problem that has hindered the analysis of images of tissues acquired by fluorescence microscopy. Current approaches to mitigate autofluorescence in tissue are lab-based and involve either chemical treatment of sections or specialized instrumentation and software to 'unmix' autofluorescent signals. Importantly, these approaches are pre-emptive and there are currently no methods to deal with autofluorescence in acquired fluorescence microscopy images. RESULTS: To address this, we developed Autofluorescence Identifier (AFid). AFid identifies autofluorescent pixels as discrete objects in multi-channel images post-acquisition. These objects can then be tagged for exclusion from downstream analysis. We validated AFid using images of FFPE human colorectal tissue stained for common immune markers. Further, we demonstrate its utility for image analysis where its implementation allows the accurate measurement of HIV-Dendritic cell interactions in a colorectal explant model of HIV transmission. Therefore, AFid represents a major leap forward in the extraction of useful data from images plagued by autofluorescence by offering an approach that is easily incorporated into existing workflows and that can be used with various samples, staining panels and image acquisition methods. We have implemented AFid in ImageJ, Matlab and R to accommodate the diverse image analysis community. AVAILABILITY AND IMPLEMENTATION: AFid software is available at https://ellispatrick.github.io/AFid. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Mass Cytometry Imaging for the Study of Human Diseases-Applications and Data Analysis Strategies.

High parameter imaging is an important tool in the life sciences for both discovery and healthcare applications. Imaging Mass Cytometry (IMC) and Multiplexed Ion Beam Imaging (MIBI) are two relatively recent technologies which enable clinical samples to be simultaneously analyzed for up to 40 parameters at subcellular resolution. Importantly, these "Mass Cytometry Imaging" (MCI) modalities are being rapidly adopted for studies of the immune system in both health and disease. In this review we discuss, first, the various applications of MCI to date. Second, due to the inherent challenge of analyzing high parameter spatial data, we discuss the various approaches that have been employed for the processing and analysis of data from MCI experiments.

Involuntary outpatient treatment (IOT) in Spain.

In recent decades there have been significant legislative changes in Spain. Society develops faster than laws, however, and new challenges have emerged. In 2004, the Spanish Association of Relatives of the Mentally Ill (FEAFES) proposed amending the existing legislation to allow for the implementation of involuntary outpatient treatment (IOT) for patients with severe mental illness. Currently, and after having made several attempts at change, there is no specific legislation governing the application of this measure. Although IOT may be implemented in local programmes, we consider legal regulation to be needed in this matter.

Impact of involuntary out-patient commitment on reducing hospital services: 2-year follow-up.

Aims and method To evaluate whether involuntary out-patient commitment (OPC) in patients with severe mental disorder reduces their use of hospital services. This is a retrospective case-control study comparing a group of patients on OPC (n = 75) and a control group (n = 75) which was composed of patients whose sociodemographic variables and clinical characteristics were similar to those of the OPC group. Each control case is paired with an OPC case, so the control case must have an involuntary admission in the month that the index OPC case admission occurred. Emergency room visits, admissions and average length of hospital stay over a 2-year follow-up after the initiation of OPC were compared. Results No statistically significant evidence was found in the use of mental healthcare services between the two groups. Different reasons for admission found between the groups limit similarity when comparing the two. Clinical implications The findings cast doubt over the effectiveness of this legal measure to reduce emergency visits, the number of admissions and the length of stay in the hospital.

Involuntary outpatient treatment in patients with severe mental illness: a one-year follow-up study.

INTRODUCTION: Involuntary outpatient treatment (IOT) aims to ensure adherence to therapy in patients with serious mental disease who are unaware of their illness and for whom treatment discontinuation carries a high risk of relapse. OBJECTIVES: To evaluate the effectiveness of IOT in preventing relapse among patients with serious mental disease. METHOD: A retrospective observational study was carried out on all of the patients (n=140) receiving IOT in the city of Valencia, Spain. Hospital service uses (emergency care, admissions and mean stay times) during the 12 months before and after the introduction of IOT were compared. RESULTS: Patients with schizophrenia, delusional disorder or schizoaffective disorder showed a significant reduction in the number of admissions and days spent in the psychiatry ward during the year of IOT. The reduction in the number of visits to the emergency department was only significant for the patients with schizophrenia. DISCUSSION: We conclude that involuntary outpatient treatment may be effective for patients with serious mental disease who are unaware of their illness and for whom treatment discontinuation carries a high risk of relapse.

Involuntary outpatient treatment (iot) for severe mental patients: current situation in Spain.

Involuntary Outpatient Treatment (IOT) expects to improve treatment compliance and, therefore, prevent the impairment of patients with severe mental illness, as well as the risk for them and others. Besides IOT introduction defenders and opponent's states, scientific literature offers contradictory results. Legislative changes have been taken in the vast majority of our neighbouring countries in order to regulate IOT application. There is no legal regulation in Spain; however, OIT application is possible in certain Spanish cities. This article reviews IOT in Spain and surrounding countries.

[Evaluation of the efficacy of involuntary outpatient treatment in reducing the use of mental health services in hospital]. / Evaluación de la eficacia del tratamiento ambulatorio involuntario para reducir la atención hospitalaria.

OBJECTIVE: To determine whether psychiatric patients in involuntary outpatient treatment (IOT) show reduced use of mental health services in hospital compared with a control group not subject to a judicial order. METHOD: We compared a group of patients in IOT (n=38) with a control group (n=38), selected from involuntarily hospitalized patients during the same period. Patients in the control group had similar sociodemographic, clinical and psychiatric characteristics to the group with IOT. We analyzed the number of emergencies, inpatient admissions and length of hospital stay during a follow-up period of 6 months after the beginning of the judicial order in the IOT group or after hospital discharge in the control group. RESULTS: No significant differences were found between the IOT and the control group in hospital use (number of emergencies, inpatient admissions and mean length of hospital stay). CONCLUSIONS: These results question the efficacy of IOT to reduce the use of hospital services.

Melatonin levels in Parkinson's disease: drug therapy versus electrical stimulation of the internal globus pallidus.

The objective of our work was to measure plasma melatonin levels in patients with Parkinson's Disease (PD) following electrical stimulation of the internal globus pallidus (GPi), and to compare these levels with groups of PD patients under drug therapy and healthy controls. The levels of melatonin were measured twice daily at 1000 and 1200. The GPi stimulation at 130 Hz lowered melatonin levels, while no changes were observed in the absence of stimulation. The melatonin levels from healthy subjects were lower than those observed in PD patients. The melatonin levels from PD patients under drug therapy were also measured during the night (2000-2400-0400) and at 0800 in order to observe their circadian changes. The Internal Globus Pallidus (GPi) stimulation was effective in lowering the melatonin levels during the day and, therefore returned these levels to those observed in normal subjects.