The Mental Health of Emerging Adults: Hostile Home Environments and COVID-19.

Purpose: Due to shifts in societal and educational expectations alongside the COVID-19 pandemic, many emerging adults live with their family of origin for extended periods of time. Little is known about patterns of parent-perpetrated maltreatment in emerging adulthood. Therefore, this study evaluates the relation between forms of parent-perpetrated maltreatment, including economic abuse, and COVID stress, on symptoms of depression, anxiety, and traumatic stress. Method: 423 emerging adults who were enrolled in college in the United States in March of 2020 were recruited via MTurk to complete an online survey. An age-related COVID questionnaire and six empirically validated measures assess levels of COVID-19 exposure, lifetime maltreatment, economic abuse, and mental health status. Results: 13.0% of participants reported maltreatment that most recently occurred over the age of 18 in their household of origin. Mean COVID stress level was found to be significantly higher in the Maltreated Over 18 group compared to the Never Maltreated group (t(345) = -3.03, p = 0.003), and in the Maltreated Under 18 group compared to the Never Maltreated group (t(346) = -3.20, p = 0.002). In accounting for the contribution of demographic variables, maltreatment chronicity, economic abuse, and COVID stress, our model predicted 38.6% of variance in depression symptoms, 37.2% of variance in anxiety symptoms, and 42.9% of variance in traumatic stress. Conclusions: Findings indicate need for increased maltreatment screenings within the emerging adult population and calls for age-specific interventions to address the mental health disparities experienced by emerging adults with maltreatment histories.

Comparison of two patients presenting with the clear cell variant of urothelial cell carcinoma of the urinary bladder: laser-assisted partial cystectomy for local disease versus chemotherapy for locally advanced disease.

A 43-year-old woman and a 73-year-old man were referred separately from primary care to the urology service with short histories of frank haematuria. In both cases, histology from transurethral resection of their bladder tumours demonstrated the rare clear cell variant of urothelial/transitional cell carcinoma. Staging scans found the former patient had low-volume local disease, and the latter had locally advanced disease. The former patient went on to have partial cystectomy and pelvic lymph node dissection (with the endoscopic portion of the partial cystectomy undertaken by holmium:YAG laser), while the latter was found to have inoperable disease, and proceeded to chemotherapy. The former patient was alive with no evidence of disease recurrence at 45 months, while the latter was alive but with extensive lymph nodal recurrence at 45 months.

Histological evaluation of AMPK signalling in primary breast cancer.

BACKGROUND: AMP-activated protein kinase (AMPK) acts as a cellular fuel gauge that responds to energy stress by suppressing cell growth and biosynthetic processes, thus ensuring that energy-consuming processes proceed only if there are sufficient metabolic resources. Malfunction of the AMPK pathway may allow cancer cells to undergo uncontrolled proliferation irrespective of their molecular energy levels. The aim of this study was to examine the state of AMPK phosphorylation histologically in primary breast cancer in relation to clinical and pathological parameters. METHODS: Immunohistochemistry was performed using antibodies to phospho-AMPK (pAMPK), phospho-Acetyl Co-A Carboxylase (pACC) an established target for AMPK, HER2, ERalpha, and Ki67 on Tissue Micro-Array (TMA) slides of two cohorts of 117 and 237 primary breast cancers. The quick score method was used for scoring and patterns of protein expression were compared with clinical and pathological data, including a minimum 5 years follow up. RESULTS: Reduced signal, compared with the strong expression in normal breast epithelium, using a pAMPK antibody was demonstrated in 101/113 (89.4%) and 217/236 (91.9%) of two cohorts of patients. pACC was significantly associated with pAMPK expression (p = 0.007 & p = 0.014 respectively). For both cohorts, reduced pAMPK signal was significantly associated with higher histological grade (p = 0.010 & p = 0.021 respectively) and axillary node metastasis (p = 0.061 & p = 0.039 respectively). No significant association was found between pAMPK and any of HER2, ERalpha, or Ki67 expression, disease-free survival or overall survival. CONCLUSION: This study extends in vitro evidence through immunohistochemistry to confirm that AMPK is dysfunctional in primary breast cancer. Reduced signalling via the AMPK pathway, and the inverse relationship with histological grade and axillary node metastasis, suggests that AMPK re-activation could have therapeutic potential in breast cancer.

A candidate molecular signature associated with tamoxifen failure in primary breast cancer.

INTRODUCTION: Few markers are available that can predict response to tamoxifen treatment in estrogen receptor (ER)-positive breast cancers. Identification of such markers would be clinically useful. We attempted to identify molecular markers associated with tamoxifen failure in breast cancer. METHODS: Eighteen initially ER-positive patients treated with tamoxifen requiring salvage surgery (tamoxifen failure [TF] patients) were compared with 17 patients who were disease free 5 years after surgery plus tamoxifen adjuvant therapy (control patients). cDNA microarray, real-time quantitative PCR, and immunohistochemistry on tissue microarrays were used to generate and confirm a gene signature associated with tamoxifen failure. An independent series of 33 breast tumor samples from patients who relapsed (n = 14) or did not relapse (n = 19) under tamoxifen treatment from a different geographic location was subsequently used to explore the gene expression signature identified. RESULTS: Using a screening set of 18 tumor samples (from eight control patients and 10 TF patients), a 47-gene signature discriminating between TF and control samples was identified using cDNA arrays. In addition to ESR1/ERalpha, the top-ranked genes selected by statistical cross-analyses were MET, FOS, SNCG, IGFBP4, and BCL2, which were subsequently validated in a larger set of tumor samples (from 17 control patients and 18 TF patients). Confirmation at the protein level by tissue microarray immunohistochemistry was observed for ER-alpha, gamma-synuclein, and insulin-like growth factor binding protein 4 proteins in the 35 original samples. In an independent series of breast tumor samples (19 nonrelapsing and 14 relapsing), reduced expression of ESR1/ERalpha, IGFBP4, SNCG, BCL2, and FOS was observed in the relapsing group and was associated with a shorter overall survival. Low mRNA expression levels of ESR1/ERalpha, BCL2, and FOS were also associated with a shorter relapse-free survival (RFS). Using a Cox multivariate regression analysis, we identified BCL2 and FOS as independent prognostic markers associated with RFS. Finally, the BCL2/FOS signature was demonstrated to have more accurate prognostic value for RFS than ESR1/ERalpha alone (likelihood ratio test). CONCLUSIONS: We identified molecular markers including a BCL2/FOS signature associated with tamoxifen failure; these markers may have clinical potential in the management of ER-positive breast cancer.

Kikuchi's disease displaying a t(2:16) chromosomal translocation.

Kikuchi's disease is a rare self-limiting lymphoproliferative condition of unknown aetiology, characterised by acute or subacute necrotising lymphadenitis. It is a benign condition that can mimic malignant lymphoma. In this report, a case of Kikuchi's disease associated with a chromosomal abnormality is described. This is the first report in the literature of such a case and it highlights an important learning point; benign lymphoproliferative conditions can be associated with chromosomal abnormalities that are more typically associated with malignant lymphoproliferative conditions such as malignant lymphoma. The report illustrates the necessity for interpreting cytogenetic data in the relevant clinical and histopathological context in a multidisciplinary setting to avoid misdiagnosis and inappropriate treatment.

A simple and rapid approach to the problem of tissue contamination and patient identity in histopathologic specimens.

Individual pathologists deal with thousands of diagnostic biopsy and excision specimens annually. At each stage, procedures are in place to limit the possibility of human error, which could result in specimen transposition or contamination. One specimen contaminating another is usually easily identified and rarely causes diagnostic difficulty; however, when it does, the consequences can be very serious. We discuss 5 cases in which concerns over specimen identity and tissue contamination arose and the methodology by which we resolved those concerns. Polymerase chain reaction analysis of each case was carried out using a panel of 12 polymorphic microsatellite markers, specific for chromosomes 13, 18, and 21. These markers are routinely used in the molecular genetics diagnostic laboratory for rapid trisomy screening. In each case, the question of error was satisfactorily resolved. Using this approach, we prevented the real possibility of patients undergoing second invasive procedures. We suggest that this or a similar methodology become a routine part of pathology practice.