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.

Family Conflicts Are Bitter Splits That Hurt: A Qualitative Inquiry Toward Understanding the Impact of Family Issues in Functional Neurological Symptom Disorder.

Functional Neurological Symptom Disorder (FNSD) or Conversion Disorder, is a fairly common diagnosis among mental health patients in Pakistan. Despite its prevalence there's a dearth of research on the phenomenon, particularly on the experience of FNSD. The study was conducted with the aim to ascertain the lived experiences of individuals with Functional Neurological Symptom Disorder (FNSD) around stressful situations in their families in Pakistan. For this purpose, a total sample of 10 participants (Women = 8; Men = 2) were recruited from the psychiatry department of a tertiary care hospital in Lahore, Pakistan. Semi-structured interviews were conducted and analyzed through Interpretative Phenomenological Analysis (IPA). The two main themes revealed in the analyses were quarrels and unexpressed emotions. The sub-themes of quarrels included quarrels with family members, quarrels within family, parental/marital discord, and quarrels with extended family members. The subthemes for unexpressed emotions were hurt, anger, sadness, and jealousy. In conclusion, this study revealed that in Pakistan, stressors related to family serve as significant contributing factors in the development of FNSD.

Mediating role of body image between sexual functioning and marital intimacy in Pakistani women with breast cancer.

OBJECTIVE: The current study aimed to explore the mediating role of body image (dissatisfaction) between sexual functioning (SF) and marital intimacy in Pakistani women with breast cancer. DESIGN/PARTICIPANTS: Correlation research design was used. One hundred and eighteen women suffering from breast cancer with age (M = 39.58, SD = 11.06) were taken from both Government and Private Hospitals of Lahore, Pakistan. The participants were asked to fill out a set of questionnaires including a Demographic Form, Female Sexual Function Index, Body Image Scale, and Marital Intimacy Questionnaire (MIQ). FINDINGS: Correlation analysis revealed that there was a significant positive relationship between higher SF and positive determinants of marital intimacy (consensus, openness, affection, and commitment). Body image dissatisfaction had a negative relationship with positive determinants of marital intimacy and positive relationship with intimacy problems (dimension of MIQ). SPSS (Process) revealed that SF came out to be a positive predictor of marital intimacy while body image (dissatisfaction) came out to be a negative predictor of positive dimensions of marital intimacy. There was a mediational role of body image (dissatisfaction) between SF and all dimensions of marital Intimacy. CONCLUSION: It was concluded that women who perceived their bodies positively had better marital intimacy, which lead to a healthy marital life.

Mechanisms of ST Elevation Myocardial Infarction in Patients Hospitalized for Noncardiac Conditions.

ST elevation myocardial infarction (STEMI) occurring in patients hospitalized for a noncardiac condition is associated with a high mortality rate and thus we sought to determine the mechanisms underlying STEMI in this patient population. This is a single center retrospective study of 70 patients who had STEMI while hospitalized on a noncardiac service and underwent coronary angiography. Thrombotic in-hospital STEMI was defined by angiographic or intravascular imaging evidence of intracoronary thrombus, plaque rupture, or stent thrombosis. Thirty-six (51%) inpatient STEMIs developed in the operating room or various postoperative stages and 6 (9%) after endoscopy or a percutaneous procedure. Thrombotic etiologies were found in 39 (56%) patients. Nonthrombotic etiologies included vasospasm, supply-demand mismatch, and takotsubo cardiomyopathy. Patients in the thrombotic group were more likely to have antiplatelet medications discontinued on admission, had higher peak troponin levels and were more likely to undergo percutaneous coronary intervention than patients in the nonthrombotic group. Exposure to vasopressors, time from ECG to angiography, post-STEMI ejection fraction, length of stay, and in-hospital mortality were similar in both groups. There was no difference in the use of percutaneous coronary intervention in patients but longer ECG to coronary angiography times and fivefold higher in-hospital mortality in thrombotic inpatient STEMI compared with 643 patients who presented with an out-of-hospital STEMI during the same time period. In conclusion, thrombotic and nonthrombotic mechanisms cause STEMI in hospitalized patients and are associated with a high mortality.

Hemopericardium and Cardiac Tamponade Secondary to Migrated Inferior Vena Cava Filter.

A 73-year-old female presented with cardiogenic shock secondary to hemopericardium and cardiac tamponade. Imaging revealed two fractured legs of an inferior vena cava filter, with one leg within the anterior myocardium of the right ventricle and another penetrating the inferior septum through the middle cardiac vein. Hemopericardium and cardiac tamponade were treated with pericardiocentesis. A multidisciplinary meeting resulted in deferring further action against the embedded fractured legs of the filter with consideration of the patient's age and comorbidities. This case report should alert clinicians to think about hemopericardium as a cause of cardiac tamponade and cardiogenic shock in a patient with a history of an inferior vena cava filter placement.

Hybrid Epicardial-Endocardial Approach to Atrial Fibrillation Ablation.

WHO SHOULD UNDERGO HYBRID AF ABLATION?: Patients with symptomatic persistent or long-standing persistent atrial fibrillation refractory to pharmacological or routine catheter ablation can be considered for hybrid epicardial-endocardial AF ablation. Although it seems clear that patient selection should be important when considering hybrid AF ablation for optimal results, unfortunately, available data on the outcomes of hybrid epicardial-endocardial ablation is limited. Hybrid ablation is rarely compared to stand-alone catheter ablation, the surgical approach (access site, lesion set, ablation tool) is inconsistent, and the patient population studied is often suitable for a catheter ablation approach (paroxysmal AF, minimal structural heart disease). We believe that the hybrid approach should be considered in patients who either have had unsuccessful catheter ablations or have significant structural heart disease evident by enlarged left atrial size or atrial fibrosis. These are the patients who warrant the added risk of a hybrid approach and who stand to benefit from a more extensive ablation including isolation of the posterior wall of the left atrium. Multi-center studies with a uniform hybrid ablation approach and comparison with a stand-alone catheter ablation approach are needed to help clarify the role of hybrid AF ablation.

Posterior Wall Isolation in Atrial Fibrillation Ablation.

Catheter ablation is widely utilized for the management of atrial fibrillation (AF), particularly in patients who are refractory to medical therapy. The left atrium appears to play a dominant role in the condition of most patients with AF and, in particular, the posterior wall and pulmonary veins frequently harbor sources of fibrillation. Currently, the role of posterior wall isolation during catheter ablation of AF is controversial. In this review, we will examine the mechanistic role of the posterior left atrium, discuss the technical challenges of ablating in the posterior wall and the evolution of strategies to achieve isolation with catheter approaches, and review the relevant literature to date.

Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells.

Biallelic inactivation of cancer susceptibility gene BRCA1 leads to breast and ovarian carcinogenesis. Paradoxically, BRCA1 deficiency in mice results in early embryonic lethality, and similarly, lack of BRCA1 in human cells is thought to result in cellular lethality in view of BRCA1's essential function. To survive homozygous BRCA1 inactivation during tumorigenesis, precancerous cells must accumulate additional genetic alterations, such as p53 mutations, but this requirement for an extra genetic "hit" contradicts the two-hit theory for the accelerated carcinogenesis associated with familial cancer syndromes. Here, we show that heterozygous BRCA1 inactivation results in genomic instability in nontumorigenic human breast epithelial cells in vitro and in vivo. Using somatic cell gene targeting, we demonstrated that a heterozygous BRCA1 185delAG mutation confers impaired homology-mediated DNA repair and hypersensitivity to genotoxic stress. Heterozygous mutant BRCA1 cell clones also showed a higher degree of gene copy number loss and loss of heterozygosity in SNP array analyses. In BRCA1 heterozygous clones and nontumorigenic breast epithelial tissues from BRCA mutation carriers, FISH revealed elevated genomic instability when compared with their respective controls. Thus, BRCA1 haploinsufficiency may accelerate hereditary breast carcinogenesis by facilitating additional genetic alterations.

Deletion of PTEN promotes tumorigenic signaling, resistance to anoikis, and altered response to chemotherapeutic agents in human mammary epithelial cells.

Many cancers, including breast cancer, harbor loss-of-function mutations in the catalytic domain of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) or have reduced PTEN expression through loss of heterozygosity and/or epigenetic silencing mechanisms. However, specific phenotypic effects of PTEN inactivation in human cancer cells remain poorly defined without a direct causal connection between the loss of PTEN function and the development or progression of cancer. To evaluate the biological and clinical relevance of reduced or deleted PTEN expression, a novel in vitro model system was generated using human somatic cell knockout technologies. Targeted homologous recombination allowed for a single and double allelic deletion, which resulted in reduced and deleted PTEN expression, respectively. We determined that heterozygous loss of PTEN in the nontumorigenic human mammary epithelial cell line MCF-10A was sufficient for activation of the phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase pathways, whereas the homozygous absence of PTEN expression led to a further increased activation of both pathways. The deletion of PTEN was able to confer growth factor-independent proliferation, which was confirmed by the resistance of the PTEN(-/-) MCF-10A cells to small-molecule inhibitors of the epidermal growth factor receptor. However, neither heterozygous nor homozygous loss of PTEN expression was sufficient to promote anchorage-independent growth, but the loss of PTEN did confer apoptotic resistance to cell rounding and matrix detachment. Finally, MCF-10A cells with the reduction or loss of PTEN showed increased susceptibility to the chemotherapeutic drug doxorubicin but not paclitaxel.

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.