Addressing the elephant in the room: understanding functional neurological symptom disorder through the lens of culture and religion.

Owing to the dearth of scholarly works to understand the presence of Functional Neurological Symptom Disorder (FNSD) among mental health patients in Pakistan, this study sought to understand how cultural and religious conflicts are implicated in the aetiology of FNSD. The study recruited 22 participants, comprising five men and 17 women. The participants were recruited from the Department of Psychiatry at Services Hospital, Lahore, Pakistan. Semi-structured interviews were conducted and analyzed through Thematic Analysis. The two main themes identified in this study were cultural and religious values and beliefs about romantic relationships. Within the cultural and religious values theme, subthemes of self-perception, a conviction in religious beliefs, and sexual suppression were identified. Furthermore, the subthemes of beliefs about romantic relationships were family's approval, engagement against wishes, and fear of exposure. The two main themes are interconnected: beliefs about romantic relationships were interpreted and experienced through the perspective of religion and culture. To summarize, this study concluded that stressors related to culture and religion are significant contributing factors in the development of FNSD. This study has important implications for mental health professionals, as awareness around the interplay of cultural as well as religious beliefs and FNSD will enable them to devise effective and holistic therapeutic intervention.

High-throughput screening identifies novel agents eliciting hypersensitivity in Fanconi pathway-deficient cancer cells.

Inactivation of the Fanconi anemia (FA) pathway occurs in diverse human tumors among the general population and renders those tumors hypersensitive to DNA interstrand-cross-linking (ICL) agents. The identification of novel agents to which FA pathway-deficient cells were hypersensitive could provide new therapeutic opportunities and improve our molecular understanding of the FA genes. Using high-throughput screening, we assessed the growth of isogenic human cancer cells that differed only in the presence or absence of single FA genes upon treatment with 880 active drugs and 40,000 diverse compounds. We identified several compounds to which FA pathway-deficient cells were more sensitive than FA pathway-proficient cells, including two groups of structurally related compounds. We further investigated the compound eliciting the strongest effect, termed 80136342. Its mechanism of action was distinct from that of ICL agents; 80136342 did not cause increased chromosomal aberrations, enhanced FANCD2 monoubiquitination, H2AX phosphorylation, p53 activation, or ICL induction. Similar to ICL agents, however, 80136342 caused a pronounced G(2) arrest in FA pathway-deficient cells. When applied in combination with ICL agents, 80136342 had at least additive toxic effects, excluding interferences on ICL-induced toxicity and facilitating a combinational application. Finally, we identified one particular methyl group necessary for the effects of 80136342 on FA-deficient cells. In conclusion, using high-throughput screening in an isogenic human FA cancer model, we explored a novel approach to identify agents eliciting hypersensitivity in FA pathway-deficient cells. We discovered several attractive candidates to serve as lead compounds for evaluating structure-activity relationships and developing therapeutics selectively targeting FA pathway-deficient tumors.