Perspectives of healthcare providers, service users, and family members about mental illness stigma in primary care settings: A multi-site qualitative study of seven countries in Africa, Asia, and Europe

Background: Stigma among healthcare providers is a barrier to the effective delivery of mental health services in primary care. Few studies have been conducted in primary care settings comparing the attitudes of healthcare providers and experiences of people with mental illness who are service users in those facilities. Such research is necessary across diverse global settings to characterize stigma and inform effective stigma reduction. Methods: Qualitative research was conducted on mental illness stigma in primary care settings in one low-income country (Nepal), two lower-middle income countries (India, Tunisia), one upper-middle-income country (Lebanon), and three high-income countries (Czech Republic, Hungary, Italy). Qualitative interviews were conducted with 248 participants: 64 primary care providers, 11 primary care facility managers, 111 people with mental illness, and 60 family members of people with mental illness. Data were analyzed using framework analysis. Results: Primary care providers endorsed some willingness to help persons with mental illness but reported not having appropriate training and supervision to deliver mental healthcare. They expressed that people with mental illness are aggressive and unpredictable. Some reported that mental illness is incurable, and mental healthcare is burdensome and leads to burnout. They preferred mental healthcare to be delivered by specialists. Service users did not report high levels of discrimination from primary care providers; however, they had limited expectations of support from primary care providers. Service users reported internalized stigma and discrimination from family and community members. Providers and service users reported unreliable psychiatric medication supply and lack of facilities for confidential consultations. Limitations of the study include conducting qualitative interviews in clinical settings and reliance on clinician-researchers in some sites to conduct interviews, which potentially biases respondents to present attitudes and experiences about primary care services in a positive manner. Conclusions: Primary care providers' willingness to interact with people with mental illness and receive more training presents an opportunity to address stigmatizing beliefs and stereotypes. This study also raises important methodological questions about the most appropriate strategies to accurately understand attitudes and experiences of people with mental illness. Recommendations are provided for future qualitative research about stigma, such as qualitative interviewing by non-clinical personnel, involving non-clinical staff for recruitment of participants, conducting interviews in non-clinical settings, and partnering with people with mental illness to facilitate qualitative data collection and analysis

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Porous Texture of CuO Prepared from Copper Oxalate Precursor

The porous texture of CuO obtained from CuC 2 O 4 • 0.5H 2 O as a precursor, as well as the interconnection between the texture of the initial oxalate and that of the copper oxide obtained, has been studied by physisorption, XRD, XPS and SEM methods. The dimensions of the particle aggregates and the crystalline particles were altered as a consequence of the thermal decomposition of CuC 2 O 4 • 0.5H 2 O to CuO, and this led to an increase of ca. 1.5-times in the specific surface of the CuO obtained relative to that of the initial substance. The comparatively non-uniform sizes of the intra-aggregate mesopores in CuC 2 O 4 • 0.5H 2 O were transformed into considerably smaller intra-aggregate mesopores in CuO. A finite increase in the volume of the intra-crystallite pores in CuO was also observed, although this did not change the average size of the intra-crystallite pores in the oxide obtained nor the character of the pore-size distribution with respect to the starting material. In addition, as a result of the thermal decomposition of CuC 2 O 4 • 0.5H 2 O, the mesoporosity of the prepared oxide also developed. However, the CuO component retained the textural type characteristic of the initial CuC 2 O 4 • 0.5H 2 O

Renal Changes in Cocaine Abuse and Addiction

Cocaine is a natural alkaloid extracted from the leaves of the South American plant Erythroxylum coca or synthesized chemically. After cannabis, it is the second most frequently abused recreational substance worldwide. Cocaine can affect every tissue and organ within the human body, including the kidneys, causing tissue ischemia due to vasoconstriction, endothelial dysfunction and damage, procoagulant activity and oxidative stress with subsequent ischemic infarctions and fibrosis. The renal changes in cocaine abuse and addiction are due to rhabdomyolysis, ischemic, hypertensive, and inflammatory changes with the development of cell proliferation and fibrosis. The authors present three patients with cocaine-associated renal damage and discuss the underlying mechanisms of cocaine-induces tissue changes

Acute Kidney Injury and Acute Renal Failure in Coronaviral Infection

In December 2019 a newly described single-stranded coronavirus, later named SARS-CoV-2, started its expansion around the world and subsequently caused a global pandemic, affecting the lives of millions of people worldwide. SARS-CoV-2 can bind multiple receptors on different cells and thus invade many target organs, including the respiratory and gastrointestinal mucous membranes, lungs, central nervous system, heart, etc. This virus can affect the kidney tissue both directly and as a consequence of other organ involvement or of the treatment administered, causing acute kidney injury and leaving long term squeals that worsen the prognosis. We describe three patients with acute kidney injury and subsequent acute renal failure at the background of coronaviral infection

Dependence of the textural properties and surface species of ZnO photocatalytic materials on the type of precipitating agent used in the hydrothermal synthesis

Three different precipitating agents (NaOH, NH4(H)CO3 and CO(NH2)2) have been applied for the hydrothermal synthesis of ZnO powder materials, aiming at obtaining various types of porosity and surface species on ZnO. The synthesis procedures were carried out in the presence and in the absence of tri-block copolymer Pluronic (P123, EO20PO70EO20). These materials were characterized by powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM)–energy-dispersive X-ray spectroscopy (EDX), BET method and TG–differential thermal analysis (DTA) method, and their photocatalytic activities were tested in the removal of azo dye Reactive Black 5 (RB5). The urea precipitant yields spongy-like surface forms and the greatest share of mesopores. It has the highest specific surface area, the highest degree of crystallinity of wurtzite ZnO phase and largest content of surface OH groups in comparison with the other two precipitants. The zinc hydroxycarbonate intermediate phase is missing in the case of NaOH as a precipitating agent; therefore, it manifests poorer textural characteristics. The morphology of P123-modified sample is different and consists of needle-shaped particles. The urea-precipitated samples display superior performance in the photocatalytic oxidation reaction, compared with the other precipitated samples. The other two precipitating agents are inferior in regard to their photocatalytic activity due to a greater share of micropores (not well-illuminated inner surface) and different surface morphologies

Perspectives of healthcare providers, service users, and family members about mental illness stigma in primary care settings: A multi-site qualitative study of seven countries in Africa, Asia, and Europe

&lt;jats:sec id="sec001"&gt; &lt;jats:title&gt;Background&lt;/jats:title&gt; &lt;jats:p&gt;Stigma among healthcare providers is a barrier to the effective delivery of mental health services in primary care. Few studies have been conducted in primary care settings comparing the attitudes of healthcare providers and experiences of people with mental illness who are service users in those facilities. Such research is necessary across diverse global settings to characterize stigma and inform effective stigma reduction.&lt;/jats:p&gt; &lt;/jats:sec&gt; &lt;jats:sec id="sec002"&gt; &lt;jats:title&gt;Methods&lt;/jats:title&gt; &lt;jats:p&gt;Qualitative research was conducted on mental illness stigma in primary care settings in one low-income country (Nepal), two lower-middle income countries (India, Tunisia), one upper-middle-income country (Lebanon), and three high-income countries (Czech Republic, Hungary, Italy). Qualitative interviews were conducted with 248 participants: 64 primary care providers, 11 primary care facility managers, 111 people with mental illness, and 60 family members of people with mental illness. Data were analyzed using framework analysis.&lt;/jats:p&gt; &lt;/jats:sec&gt; &lt;jats:sec id="sec003"&gt; &lt;jats:title&gt;Results&lt;/jats:title&gt; &lt;jats:p&gt;Primary care providers endorsed some willingness to help persons with mental illness but reported not having appropriate training and supervision to deliver mental healthcare. They expressed that people with mental illness are aggressive and unpredictable. Some reported that mental illness is incurable, and mental healthcare is burdensome and leads to burnout. They preferred mental healthcare to be delivered by specialists. Service users did not report high levels of discrimination from primary care providers; however, they had limited expectations of support from primary care providers. Service users reported internalized stigma and discrimination from family and community members. Providers and service users reported unreliable psychiatric medication supply and lack of facilities for confidential consultations. Limitations of the study include conducting qualitative interviews in clinical settings and reliance on clinician-researchers in some sites to conduct interviews, which potentially biases respondents to present attitudes and experiences about primary care services in a positive manner.&lt;/jats:p&gt; &lt;/jats:sec&gt; &lt;jats:sec id="sec004"&gt; &lt;jats:title&gt;Conclusions&lt;/jats:title&gt; &lt;jats:p&gt;Primary care providers’ willingness to interact with people with mental illness and receive more training presents an opportunity to address stigmatizing beliefs and stereotypes. This study also raises important methodological questions about the most appropriate strategies to accurately understand attitudes and experiences of people with mental illness. Recommendations are provided for future qualitative research about stigma, such as qualitative interviewing by non-clinical personnel, involving non-clinical staff for recruitment of participants, conducting interviews in non-clinical settings, and partnering with people with mental illness to facilitate qualitative data collection and analysis.&lt;/jats:p&gt; &lt;/jats:sec&gt

Constitutively active GSK3beta as a means to bolster dendritic cell functionality in the face of tumour-mediated immune suppression

Contains fulltext : 215594.pdf (publisher's version ) (Open Access)In patients with cancer, the functionality of Dendritic Cells (DC) is hampered by high levels of tumor-derived suppressive cytokines, which interfere with DC development and maturation. Poor DC development can limit the efficacy of immune checkpoint blockade and in vivo vaccination approaches. Interference in intracellular signaling cascades downstream from the receptors of major tumor-associated suppressive cytokines like IL-10 and IL-6, might improve DC development and activation, and thus enhance immunotherapy efficacy. We performed exploratory functional screens on arrays consisting of >1000 human kinase peptide substrates to identify pathways involved in DC development and its inhibition by IL-10 or IL-6. The resulting alterations in phosphorylation of the kinome substrate profile pointed to glycogen-synthase kinase-3beta (GSK3beta) as a pivotal kinase in both DC development and suppression. GSK3beta inhibition blocked human DC differentiation in vitro, which was accompanied by decreased levels of IL-12p70 secretion, and a reduced capacity for T cell priming. More importantly, adenoviral transduction of monocytes with a constitutively active form of GSK3beta induced resistance to the suppressive effects of IL-10 and melanoma-derived supernatants alike, resulting in improved DC development, accompanied by up-regulation of co-stimulatory markers, an increase in CD83 expression levels in mature DC, and diminished release of IL-10. Moreover, adenovirus-mediated intratumoral manipulation of this pathway in an in vivo melanoma model resulted in DC activation and recruitment, and in improved immune surveillance and tumor control. We propose the induction of constitutive GSK3beta activity as a novel therapeutic means to bolster DC functionality in the tumor microenvironment