A Whole-genome CRISPR Screen Identifies a Role of MSH2 in Cisplatin-mediated Cell Death in Muscle-invasive Bladder Cancer

Background

The response to first-line, platinum-based treatment of muscle-invasive bladder cancer has not improved in 3 decades.

Hurtful Gifts? Trauma and Growth Transmission Among Local Clinicians in Postearthquake Haiti

Although working with trauma survivors can be a source of both deleterious and positive transformations in mental health professionals, little is known about the experience of clinicians in shared traumatic contexts, particularly in the Global South, where most humanitarian crises occur. In collective disasters or armed conflicts, the personal and professional experiences of mental health staff inform each other, situating the clinical space at the intersection between singular and collective spheres. Drawing on an intersubjective and socioecological perspective, this qualitative study explored the ways in which working in a shared traumatic context affected mental health and psychosocial staff in postearthquake Haiti. We interviewed 22 local mental health workers in the capital, Port‐au‐Prince, 2.5 years after the 2010 disaster. We coded and thematically analyzed interviews using an iterative process, based on grounded theory principles. Thematic analysis uncovered four dynamic poles in clinicians’ narratives: balancing duty and desire to help, experiencing fragility and strength, negotiating separation and connection, and sharing hurt and hope. Our findings suggest clinicians considered their work mainly as a source of strength in the face of adversity, whereas experiences of trauma and growth transmissions were mutual and intimately intertwined. We discuss the complexities of clinical work in shared traumatic settings as well as the dynamic interplay between professionals’ experiences of suffering and growth. We conclude with recommendations on ways to involve local mental health clinicians in postdisaster contexts while addressing the special needs that they may have to process their own trauma.     

Association between visual acuity,lesion activity markers and retreatment decisions in neovascular age-related macular degeneration

Background/objectivesTo investigate the association between optical coherence tomography (OCT) markers of lesion activity and changes in visual acuity (VA) during anti-vascular endothelial growth factor (anti-VEGF) therapy of eyes diagnosed with neovascular age-related macular degeneration (nAMD); and how VA and OCT markers are considered in physicians’ decision to retreat with anti-VEGFs.Subjects/methodsRetrospective, non-comparative, non-randomised cohort study involving electronic medical record data collected from 1190 patient eyes with nAMD diagnosis at two sites in the United Kingdom. Two sub-cohorts consisting of 321 and 301 eyes, respectively, were selected for analyses.ResultsIn 321 eyes, absence of IRF or SRF at ≥2 clinic visits resulted in a gain of five ETDRS letters from baseline, compared with two letters gained in eyes with <2 clinic visits with absence of IRF (p = 0.006) or SRF (p = 0.042). Anti-VEGF treatment was administered at 421 clinic visits, and 308 visits were without treatment. Comparing treatment visits with non-treatment visits, the maximum difference in frequency of OCT markers of lesion activity were for intraretinal fluid (IRF; 24% versus 5%) and subretinal fluid (SRF; 32% versus 5%). Pigment epithelial detachment (PED) was reported in 58% of treatment visits compared with 36% in non-treatment visits. VA loss was not a consistent trigger for retreatment as it was present in 63% of injection visits and in 49% of non-injection visits.ConclusionsRetreatment decision making is most strongly influenced by the presence of IRF and SRF and less by the presence of PED or VA loss.Subject terms: Outcomes research, Macular degeneration     

Functional Dosage of Muscarinic Cholinergic Receptor 3 Signalling,Not the Gene Dose,Determines Its Hypertension Pathogenesis

Background

Multiple quantitative trait loci for blood pressure (BP) have been localized throughout human and rodent genomes. Few of them have been functionally identified especially in humans, and little is known about their pathogenic directionality when identified. We focused on Chrm3 encoding the muscarinic cholinergic receptor 3 (M3R) as the causal gene for C17QTL1 in the Dahl salt-sensitive rat model.