Opening up the 'black-box': what strategies do community mental health workers use to address the social dimensions of mental health?

PURPOSE: Community-based workers promote mental health in communities. Recent literature has called for more attention to the ways they operate and the strategies used. For example, how do they translate biomedical concepts into frameworks that are acceptable and accessible to communities? How do micro-innovations lead to positive mental health outcomes, including social inclusion and recovery? The aim of this study was to examine the types of skills and strategies to address social dimensions of mental health used by community health workers (CHWs) working together with people with psychosocial disability (PPSD) in urban north India. METHODS: We interviewed CHWs (n = 46) about their registered PPSD who were randomly selected from 1000 people registered with a local non-profit community mental health provider. Notes taken during interviews were cross-checked with audio recordings and coded and analyzed thematically. RESULTS: CHWs displayed social, cultural, and psychological skills in forming trusting relationships and in-depth knowledge of the context of their client's lives and family dynamics. They used this information to analyze political, social, and economic factors influencing mental health for the client and their family members. The diverse range of analysis and intervention skills of community health workers built on contextual knowledge to implement micro-innovations in a be-spoke way, applying these to the local ecology of people with psychosocial disabilities (PPSD). These approaches contributed to addressing the social and structural determinants that shaped the mental health of PPSD. CONCLUSION: Community health workers (CHWs) in this study addressed social aspects of mental health, individually, and by engaging with wider structural factors. The micro-innovations of CHWs are dependent on non-linear elements, including local knowledge, time, and relationships. Global mental health requires further attentive qualitative research to consider how these, and other factors shape the work of CHWs in different locales to inform locally appropriate mental health care.

Mutuality as a method: advancing a social paradigm for global mental health through mutual learning.

PURPOSE: Calls for "mutuality" in global mental health (GMH) aim to produce knowledge more equitably across epistemic and power differences. With funding, convening, and publishing power still concentrated in institutions in the global North, efforts to decolonize GMH emphasize the need for mutual learning instead of unidirectional knowledge transfers. This article reflects on mutuality as a concept and practice that engenders sustainable relations, conceptual innovation, and queries how epistemic power can be shared. METHODS: We draw on insights from an online mutual learning process over 8 months between 39 community-based and academic collaborators working in 24 countries. They came together to advance the shift towards a social paradigm in GMH. RESULTS: Our theorization of mutuality emphasizes that the processes and outcomes of knowledge production are inextricable. Mutual learning required an open-ended, iterative, and slower paced process that prioritized trust and remained responsive to all collaborators' needs and critiques. This resulted in a social paradigm that calls for GMH to (1) move from a deficit to a strength-based view of community mental health, (2) include local and experiential knowledge in scaling processes, (3) direct funding to community organizations, and (4) challenge concepts, such as trauma and resilience, through the lens of lived experience of communities in the global South. CONCLUSION: Under the current institutional arrangements in GMH, mutuality can only be imperfectly achieved. We present key ingredients of our partial success at mutual learning and conclude that challenging existing structural constraints is crucial to prevent a tokenistic use of the concept.

Escherichia coli, a common constituent of benign prostate hyperplasia-associated microbiota induces inflammation and DNA damage in prostate epithelial cells.

BACKGROUND: The role of microbiota in the pathophysiology of benign prostate hyperplasia (BPH), especially in creating an inflammatory milieu may not be avoided. The major objectives of this study were to investigate the microbial composition of BPH tissues, its association with inflammation and check the effect of clinically isolated bacteria on prostate epithelial cells. METHODS: The study includes 36 patients with a pathological diagnosis of BPH. Following strict aseptic measures, tissues were collected after transurethral resection of prostate, multiple pieces of the resected tissues were subjected to histopathological analysis, bacterial culture and genomic DNA extraction. Microbial composition was analyzed by culture and/or next-generation sequencing methods. Annotation of operational taxonomy unit has been done with an in-house algorithm. The extent of inflammation was scored through histological evaluation of tissue sections. The effect of clinical isolates on nuclear factor-κB (NF-κB) activity and induction of DNA-damage in the prostate epithelial cells were evaluated. RESULTS: Histopathological analysis of the BPH tissues showed the presence of inflammation in almost all the tissues with a varied level at different regions of the same tissue section and the level of overall inflammation was different from patients to patients. Microbial culture of tissue samples showed the presence of live bacteria in 55.5% (20 out of 36) of the patient tissues. Majority of the isolates were coagulase-positive Staphylococcus, E. coli and Micrococcus spp. Further, V3 16S rRNA sequencing of the DNA isolated from BPH tissues showed the presence of multiple bacteria and the most common phylum in the BPH tissues were found to be Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. The E. coli, isolated from one of the tissue was able to activate NF-κB and induce DNA damage in prostate epithelial cells. Phospho-histone γH2A.X staining confirmed the presence of cells with damaged DNA lesion in BPH tissues and also correlated with the severity of inflammation. CONCLUSION: Our study has shown that the BPH tissues do have a divergent microbial composition including the commonly found E. coli (phylum Proteobacteria), and these bacteria might contribute to the BPH-associated inflammation and/or tissue damage. The BPH-associated E. coli induced NF-κB signaling and DNA damage in prostate epithelial cells in vitro.

Co-production of a pictorial recovery tool for people with psycho-social disability informed by a participatory action research approach-a qualitative study set in India.

Mental health problems are recognized as a leading cause of disability and have seen increased allocations of resources and services globally. There is a growing call for solutions supporting global mental health and recovery to be locally relevant and built on the knowledge and skills of people with mental health problems, particularly in low-income countries. Set in Dehradun district, North India, this study aimed to describe first, the process of co-production of a visual tool to support recovery for people affected by psycho-social disability; second, the key outputs developed and third, critical reflection on the process and outputs. The developmental process consisted of participatory action research and qualitative methods conducted by a team of action researchers and an experts by experience (EBE) group of community members. The team generated eight domains for recovery under three meta-domains of normalcy, belonging and contributing and the ensuing recovery tool developed pictures of activities for each domain. Challenges to using a participatory and emancipatory process were addressed by working with a mentor experienced in participatory methods, and by allocating time to concurrent critical reflection on power relationships. Findings underline the important contribution of an EBE group demonstrating their sophisticated and locally valid constructions of recovery and the need for an honest and critically reflective process in all co-productive initiatives. This study generated local conversations around recovery that helped knowledge flow from bottom-to-top and proposes that the grass-root experiences of participants in a disadvantaged environment are needed for meaningful social and health policy responses.

Lipopolysaccharide (LPS) enhances prostate cancer metastasis potentially through NF-κB activation and recurrent dexamethasone administration fails to suppress it in vivo.

BACKGROUND: Previous studies have shown the effect of bacterial lipopolysaccharide (LPS) on enhanced cancer cells' growth and metastasis. However, the effect of LPS on prostate cancer (PCa) cells metastasis has not been investigated in details. This study aimed to investigate the functional role of LPS on PCa cells metastasis and determine the effect of dexamethasone (DEX) on this event. METHODS: Two different PCa reporter cells lines (DU145-NF-κB-Luc and MAT-LyLu- NF-κB-Luc) were used to assess the direct effect of LPS on NF-κB activation in PCa cells. Plasma collected from LPS-stimulated human and rodent blood were used to check the indirect effect of LPS on NF-κB activation in PCa cells. Trans-well migration assay and two different orthotopic PCa animal models were used to investigate the effect of LPS on DU145 and MAT-LyLu cells migration or metastasis in vitro and in vivo, respectively. In all the studies DEX was used with or without LPS stimulation. RESULTS: LPS and secretory factors present in plasma collected from LPS-stimulated blood, significantly activated NF-κB in DU145, and MAT-LyLu cells and enhanced their migration in vitro. DEX significantly suppressed LPS-mediated activation of cancer and blood cells and abrogated the direct and indirect pro-migratory effect of LPS on PCa cells. Systemic administration of LPS activated NF-κB in DU145 cells in vivo; however, failed to alter the metastatic properties of these cells. On the other hand, systemic administration of LPS to MAT-LyLu tumor bearing animals significantly enhanced the incidence of metastasis without altering the overall growth of primary tumors. Unexpectedly, though DEX significantly suppressed MAT-LyLu primary tumor weights, it aggravated metastasis of cancer cells in presence and absence of LPS. Moreover, consecutive DEX pre-treatment enhanced experimental peritoneal metastasis of MAT-LyLu cells. At the molecular level, LPS, and/or DEX induced overexpression of immunosuppressive molecules in MAT-LyLu tumors. CONCLUSIONS: Overall, our study has shown that LPS and/or LPS induced inflammation can increase PCa metastasis and immunosuppressive dose of DEX might further enhance cancer metastasis.

A modified technique for fabrication of custom-made afterload brachytherapy appliance.

Radiotherapy for carcinomas that involve the mouth and its related structures has been improved by the usage of different prostheses known as radiation carriers. These prostheses can accurately position radionuclide such as radium, iridium, cesium, and cobalt to allow adequate transfer of a concentrated radiation dose to a tumor region. At the same time, they minimize the exposure to radiation of nearby tissues due to rapid fall-off the radioactivity and thus minimizing the side effects of radiation. This study emphasizes the usage of a modified technique for the development of afterload mold brachytherapy appliance for squamous cell carcinoma patients of hard palate/soft palate.

A comparative evaluation of fatigue resistance of two different implant overdenture stud attachments with two different denture base materials: An in vitro study.

INTRODUCTION: The two implant-supported overdentures have overcome the retention and stability-related problems of conventional mandibular denture. Stud attachments are widely available, less expensive, and easy to use. AIMS AND OBJECTIVES: To determine fatigue resistance of two different stud attachments with two denture base materials - autopolymerizing and heat cure acrylic resin till 4320 cycles simulating 03 years of service. MATERIALS AND METHODS: Stud implant overdenture attachments, i.e., ball and socket and Dalla Bona attachments were tightened over the implants in two different mandibular edentulous base models. The housings were incorporated with both direct (chairside) and indirect (laboratory) technique into conventional mandibular dentures. These overdentures were subjected to continuous removal and insertion on Universal Testing Machine till 4320 cycles simulating 3 years of service assuming that patient takes out denture, 4 times in a day. The fatigue resistance was calculated for 0, 1440 (1 year), 2800 (2 years), and 4320 (3 years) cycles. Unpaired and paired t-tests were applied to find the level of significance. RESULTS: Ball and socket attachments housed with heat cure acrylic resin (indirect technique) had the highest values of fatigue resistance at all cycles. Following were Dalla Bona attachments with autopolymerizing acrylic resin (direct technique), ball and socket attachments with autopolymerizing acrylic resin (direct technique), and Dalla Bona attachments with heat cure acrylic resin (indirect technique) as per statistical analysis. CONCLUSION: Two implant-supported mandibular overdenture with ball and socket attachments incorporated by indirect technique showed higher values in terms of retention and absence of disengagement/fracture of components.

Rehabilitation of orbital cavity after orbital exenteration using polymethyl methacrylate orbital prosthesis.

Squamous cell carcinoma of the eyelid is the second most common malignant neoplasm of the eye with the incidence of 0.09 and 2.42 cases/100 000 people. Orbital invasion is a rare complication but, if recognized early, can be treated effectively with exenteration. Although with advancements in technology such as computer-aided design and computer-aided manufacturing, material science, and retentive methods like implants, orbital prosthesis with stock ocular prosthesis made of methyl methacrylate retained by anatomic undercuts is quiet effective and should not be overlooked and forgotten. This clinical report describes prosthetic rehabilitation of two male patients with polymethyl methacrylate resin orbital prosthesis after orbital exenteration, for squamous cell carcinoma of the upper eyelid. The orbital prosthesis was sufficiently retained by hard and soft tissue undercuts without any complications. The patients using the prosthesis are quite satisfied with the cosmetic results and felt comfortable attending the social events.

TLR4 activation by lipopolysaccharide confers survival advantage to growth factor deprived prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) cells express Toll-like receptor-4 (TLR4), a known pro-tumorigenic molecule for different cancer cells. The cancer cells residing in the avascular region of the tumor confront various metabolic stresses and continuously adapt mechanisms to overcome them. We hypothesized that TLR4 activation might provide direct survival advantage to metabolically stressed PCa cells. METHODS: We first investigated the effect of LPS on survival of serum deprived PCa cells. To understand the molecular mechanisms involved in TLR4 mediated PCa survival, we next investigated change in expression of markers for apoptosis, senescence and autophagy. Ultimately, the effect of LPS on established prostate tumors was confirmed in vivo using a syngeneic rat model for PCa. RESULTS: Lipopolysaccharide (LPS)-mediated TLR4 activation significantly enhanced survival of serum deprived (SD) PC3, DU145 and MAT-LyLu PCa cells. TLR4 inhibition by a specific inhibitor resulted in rapid death of SD-PC3 cells, which was significantly suppressed by LPS. Interestingly, LPS treatment suppressed macroautophagy in SD-PC3 cells and increased expression of CCL2 (C-C motif ligand-2), a known autophagy inhibitor and pro-survival factor. Intra-tumor LPS injection resulted in increased tumor mass, induced TLR4 activation, suppressed autophagy, and increased the macrophage population in MAT-LyLu-tumors. CONCLUSIONS: Our study reveals that bacterial LPS enhance survival of PCa cells under conditions of nutrient stress through TLR4 activation. Moreover, LPS induces overexpression of CCL2 involved in the suppression of starvation-induced macroautophagy in PCa cells, and enhanced macrophage population in prostate tumors in vivo. Taken together, the current study suggests the importance of bacterial infection or TLR4-activation in prostate cancer pathogenesis.

Effective control of Salmonella infections by employing combinations of recombinant antimicrobial human ß-defensins hBD-1 and hBD-2.

We successfully produced two human ß-defensins (hBD-1 and hBD-2) in bacteria as functional peptides and tested their antibacterial activities against Salmonella enterica serovar Typhi, Escherichia coli, and Staphylococcus aureus employing both spectroscopic and viable CFU count methods. Purified peptides showed approximately 50% inhibition of the bacterial population when used individually and up to 90% when used in combination. The 50% lethal doses (LD50) of hBD-1 against S. Typhi, E. coli, and S. aureus were 0.36, 0.40, and 0.69 µg/µl, respectively, while those for hBD-2 against the same bacteria were 0.38, 0.36, and 0.66 µg/µl, respectively. Moreover, we observed that bacterium-derived antimicrobial peptides were also effective in increasing survival time and decreasing bacterial loads in the peritoneal fluid, liver, and spleen of a mouse intraperitoneally infected with S. Typhi. The 1:1 hBD-1/hBD-2 combination showed maximum effectiveness in challenging the Salmonella infection in vitro and in vivo. We also observed less tissue damage and sepsis formation in the livers of infected mice after treatment with hBD-1 and hBD-2 peptides individually or in combination. Based on these findings, we conclude that bacterium-derived recombinant ß-defensins (hBD-1 and hBD-2) are promising antimicrobial peptide (AMP)-based substances for the development of new therapeutics against typhoid fever.