Establishing the measurement properties of the Residential Environment Impact Scale (Version 4.0).

BACKGROUND: Developed as an environment assessment informed by the Model of Human Occupation, the Residential Environment Impact Survey considered the physical, social and activity features of the environment, evaluating the impact of the environment on resident's quality of life. Clinicians reported that the Residential Environment Impact Survey was a useful tool; however, it had not been structured to be a measurement tool and did not have established psychometric properties. AIMS/OBJECTIVES: This study examines the psychometric properties of the restructured Residential Environment Impact Scale Version 4.0 (REIS), which measures the level of environment support provided to residents. MATERIAL AND METHODS: The REIS was completed across residential sites for people with complex mental health needs. A many facets Rasch analysis was conducted to establish the reliability and validity of the REIS. RESULTS: The REIS demonstrated reasonable psychometric properties, with items demonstrating internal scale validity and scale items following an expected pattern of increasingly challenging environment support. CONCLUSIONS AND SIGNIFICANCE: Initial evidence suggests that the REIS provides a valid and reliable measure of environment support, providing a detailed assessment of how physical, social and activity elements of the environment support or inhibit participation and can be applied across a range of living environments.

The level of formal support received by people with severe mental illness living in supported accommodation and participation: A systematic review.

AIM: The review aimed to identify and explore the association of level of support received by people with severe mental illness in supported accommodation and participation. METHOD: The authors conducted a systematic search in MEDLINE, PsychINFO, PsychARTICLES, CINAHL Plus and ASSIA. Searches were restricted to articles published in English and participants aged 18 years and over with severe mental illness. Articles were included based on level of support received in mental health supported accommodation, classified according to the Simple Taxonomy for Supported Accommodation, and three factors of participation: social participation, daily living functioning and personal empowerment. Studies of in-patient settings and nursing homes were excluded. The review protocol is registered on PROSPERO (registration number: CRD42019161808). RESULTS: Six articles were included in the review from USA, Australia, Sweden and Taiwan. Factors of participation for people living in accommodation with moderate support and accommodation with high support were explored. Data indicated an association between level of support and participation showing that people living in accommodation with moderate support had increased participation compared to people living in accommodation with high support. CONCLUSION: This review identified an association between level of formal support and participation. People with SMI living in accommodation with medium support participated in more community occupations, more activities and had a higher level of personal empowerment than people living in accommodation with high support.

Quality of life outcomes for people with serious mental illness living in supported accommodation: systematic review and meta-analysis.

PURPOSE: To conduct a systematic review and meta-analysis of quality of life (QoL) outcomes for people with serious mental illness living in three types of supported accommodation. METHODS: Studies were identified that described QoL outcomes for people with serious mental illness living in supported accommodation in six electronic databases. We applied a random-effects model to derive the meta-analytic results. RESULTS: 13 studies from 7 countries were included, with 3276 participants receiving high support (457), supported housing (1576) and floating outreach (1243). QoL outcomes related to wellbeing, living conditions and social functioning were compared between different supported accommodation types. Living condition outcomes were better for people living in supported housing ([Formula: see text]= - 0.31; CI = [- 0.47; - 0.16]) and floating outreach ([Formula: see text]= - 0.95; CI = [- 1.30; - 0.61]) compared to high-support accommodation, with a medium effect size for living condition outcomes between supported housing and floating outreach ([Formula: see text]= - 0.40; CI = [- 0.82; 0.03]), indicating that living conditions are better for people living in floating outreach. Social functioning outcomes were significant for people living in supported housing compared to high support ([Formula: see text] = - 0.37; CI = [- 0.65; - 0.09]), with wellbeing outcomes not significant between the three types of supported accommodation. CONCLUSION: There is evidence that satisfaction with living conditions differs across supported accommodation types. The results suggest there is a need to focus on improving social functioning and wellbeing outcomes for people with serious mental illness across supported accommodation types.

Acute presentation of a giant intrathyroidal parathyroid adenoma: a case report.

BACKGROUND: We report the case of a giant intrathyroidal parathyroid adenoma weighing 59 g in a young woman presenting acutely with severe hypercalcemia requiring correction and adequate preoperative management prior to surgery. Parathyroid adenomas account for 85 % of cases of primary hyperparathyroidism. Those weighing more than 3.5g are classified as giant parathyroid adenomas. There are only 25 cases of parathyroid adenomas weighing over 30g reported in the literature. With the wide availability of biochemical screening tests in Western countries, mildly elevated calcium levels are often discovered incidentally. Our case is unusual for the extreme level of hypercalcemia, the patient's young age, and the weight of the adenoma, particularly in a developed country. CASE PRESENTATION: A 21-year-old Irish woman presented with a 3-week history of an enlarging right-sided neck mass. There was no dysphagia, stridor, or symptoms of hyperthyroidism or hypercalcemia. On examination, there was a firm painless swelling in the right lobe of her thyroid. Her thyroid function tests were normal. Corrected serum calcium was markedly elevated at 3.96 mmol/L with hypophosphatemia of 0.35 mmol/L. She was treated with bisphosphonates and fluids administered intravenously. Her parathyroid hormone level was over 20 times the upper limit of normal. Ultrasound revealed a solid and cystic nodule in the lower pole of the right lobe of her thyroid. Parathyroid scintigraphy demonstrated a 5×4 cm lesion which concentrated tracer. A right-sided parathyroidectomy, right thyroid lobectomy, and level VI neck dissection were performed. An encapsulated multiloculated solid cystic mass weighing 59 g was removed. There was no definite infiltration of the capsule and MIB1 count was low at 1 % thus the specimen lacked the diagnostic features of carcinoma. On the third postoperative day, hungry bone syndrome developed and calcium replacement administered intravenously was required. At 1-year postoperative, she was weaned off calcium and alfacalcidol. A follow-up ultrasound showed unremarkable residual thyroid. CONCLUSIONS: Any patient with an isolated hypercalcemia warrants a thorough work-up. Hungry bone syndrome is a potentially avoidable condition; thus the clinician should be highly attuned to the risk of hungry bone syndrome post-parathyroidectomy, which correlates with the weight of the adenoma resected.

The fate of chemoresistance in triple negative breast cancer (TNBC).

BACKGROUND: Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype. SCOPE OF REVIEW: How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed. MAJOR CONCLUSIONS: Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome. GENERAL SIGNIFICANCE: Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy.

Recurrence of urothelial carcinoma of the bladder: a role for insulin-like growth factor-II loss of imprinting and cytoplasmic E-cadherin immunolocalization.

PURPOSE: This study documents the frequency of insulin-like growth factor-II (IGF-II) loss of imprinting (LOI) in a series of 87 bladder tissues. E-cadherin (CDH1) immunolocalization was also investigated due to the known redistribution of this adherence protein to the cytoplasm following exogenous exposure to IGF-II. EXPERIMENTAL DESIGN: Informative IGF-II cases were identified following DNA-PCR amplification and subsequent sequencing of the transcribable ApaI RFLP in exon 9 of IGF-II. Similar approaches using primer-specific cDNA templates identified the imprinting status of IGF-II in these informative cases. CDH1 cellular localization was assessed on a tissue microarray platform of 114 urothelial carcinoma of the bladder (UCB) cases (70 pT(a) noninvasive and 44 pT(1) lamina propria invasive) using the commercially available Novocastra antibody. RESULTS: IGF-II LOI was evident in 7 of 17 (41%) UCB tumors and 4 of 11 (36%) tumor-associated normal urothelial samples. Two of four pT(1) grade 3 tumors, the subject of much debate concerning their suitability for radical cystectomy, showed LOI at the IGF-II locus. In those tumors showing IGF-II LOI, 4 of 7 (57%) displayed concomitant CDH1 cytoplasmic staining. In contrast, only 3 of 10 (30%) IGF-II maintenance of imprinting tumors had concomitant CDH1 cytoplasmic localization. UCB cell lines displaying cytoplasmic CDH1 immunolocalization expressed significantly higher levels of IGF-II (CAL29, HT1376, and RT112) compared with RT4, a cell line displaying crisp membranous CDH1 staining. Finally, cytoplasmic CDH1 staining was an independent predictor of a shorter time to recurrence independent of tumor grade and stage. CONCLUSIONS: We suggest that CDH1 cytoplasmic immunolocalization as a result of increased IGF-II levels identifies those nonmuscle invasive presentations most likely to recur and therefore might benefit from more radical nonconserving bladder surgery.

Progesterone receptor B (PRB) promoter hypermethylation in sporadic breast cancer: progesterone receptor B hypermethylation in breast cancer.

INTRODUCTION: Oestrogen receptor alpha (ER alpha) is traditionally measured on all breast tumour specimens to identify those patients more likely to respond to anti-oestrogens. Progesterone receptor (PR) status has contributed useful information in defining more responsive subgroups. PR negativity may be a marker for increased signalling through growth factor receptor tyrosine kinase pathways. Progesterone acts through two PRs, PRA and PRB. PRB, the functionally active PR, can be silenced by promoter hypermethylation. METHODS: Following DNA and RNA extraction from 94 breast carcinomas, the methylation status of the PRB promoter was assessed by sodium bisulphite modification and methylation sensitive PCR (MSP). A quantitative realtime PCR analysis (QRTPCR) was used to determine the levels of PRB mRNA expression. Protein expression was evaluated immunohistochemically with a commercially available PRB antibody. RESULTS: 76% of the primary breast carcinoma samples demonstrated a methylated band for PRB. PRB methylation significantly compromised total PR immunohistochemistry (IHC) expression (P = 0.03). PRB mRNA correlated positively with total PR IHC (r = 0.58, P = 0.04), ER alpha IHC (P = 0.02), and tumour grade (P = 0.01). PRB protein expression was significantly associated with a number of favourable prognostic variables including smaller (P = 0.004) lower grade (P = 0.007), ER alpha IHC positive tumours (P < 0.001), and tumours with a low Nottingham Prognostic Index (NPI) (P = 0.0008). PRB mRNA levels were significantly associated with better overall survival (P = 0.04) in a univariate analysis. CONCLUSION: The majority of tumours were methylated for PRB. This did not directly compromise PRB expression suggesting that other factors may down regulate the PR gene. When PRB was expressed, it correlated with good prognostic markers and better overall survival.

Alpha-T-catenin (CTNNA3) displays tumour specific monoallelic expression in urothelial carcinoma of the bladder.

CTNNA3 (alpha-T-catenin) is imprinted with preferential monoallelic expression of the maternal allele in placental tissue. The allelic expression pattern of CTNNA3 in adult human cancer is unknown and warrants investigation as CTNNA3 stabilizes cellular adherence, a feature which if compromised could enable cells to acquire an increased capability to detach and invade. We document the frequency of monoallelic versus biallelic expression of CTNNA3 in urothelial carcinoma of the bladder (UCB) samples and compare the observed patterns with that found in the paired normal sample. DNA PCR reactions encompassing a transcribable SNP polymorphism within exon 12 of CTNNA3 were sequence analyzed to identify heterozygous cases. A total of 96 samples were analyzed and included 22 paired normal and tumor UCB cases, 38 formalin fixed paraffin embedded (FFPE) UCB samples consisting of 18 noninvasive pTa tumors and 20 lamina propria invasive pT1 tumors and 14 cell lines of various lineages. RT-PCR analysis of 35 heterozygous samples followed by sequence analysis allowed monoallelic versus biallelic patterns to be assigned. We have provided the first demonstration that CTNNA3 displays differing allelic expression patterns in UCB. Specifically, 35% (7/20) of informative UCB, showed monoallelic expression, a feature confined to the tumor, with normal urothelial samples displaying biallelic expression. Real time RT-PCR analyses, demonstrated a significantly lower (P = 0.00039) level of CTNNA3 in the tumor samples compared with the paired normals, all of which displayed biallelic expression. In conclusion, monoallelic and biallelic CTNNA3 expression patterns are demonstrable in tumor bladder tissue, whereas normal cases show only biallelic expression.

Role of the progesterone receptor (PR) and the PR isoforms in breast cancer.

Known risk factors for breast cancer include overexposure to exogenous or endogenous hormones, namely, estrogen and progesterone. The effects of progesterone acts via two isoforms of the progesterone receptor (PR) termed A (PRA) and B (PRB). There is a single human PR gene with two distinct promoter regions in exon 1 encoding the two isoforms. Studies have shown that in poor prognostic tumors, the ratio between PRA and PRB is altered, with a predominance of PRA and loss of PRB. PRA and PRB regulate different subsets of genes involved in particular functional pathways. Breast tumors that express PR are associated with slow growth, better differentiation, and better overall prognosis in the short term. Both estrogen receptor alpha (ERalpha) and total progesterone receptor (PR) are immunohistochemically measured on breast cancer specimens to help determine those patients who would benefit from hormonal treatment. Depending on the hormone receptor status and the menopausal status of the patient, different treatments are available. Although the value of ERalpha in predicting response to hormone therapy in early breast cancer patients is undisputed, the value of PR is currently under debate. Historically, PR was thought to be a surrogate marker for ER expression; however, it is now known that lack of PR expression can indicate underlying epidermal growth factor receptor signaling or promoter methylation. This has implications for and can dictate hormone therapy responsiveness. Further studies investigating the specific isoforms and their pathways will help to reveal the underlying mechanisms of PR-induced breast tumori-genesis and help in assigning the most appropriate patient-tailored treatment.

Promoter switch: a novel mechanism causing biallelic PEG1/MEST expression in invasive breast cancer.

We have previously reported on the biallelic expression of the imprinted PEG1/MEST gene in infiltrating carcinomas of the breast. Putative loss of imprinting (LOI) of PEG1/MEST has subsequently also been implicated in the aetiology of lung adenocarcinomas and colon cancer. Taking advantage of our previous study, identifying seven infiltrating carcinomas of the breast, displaying biallelic PEG1/MEST expression, we have analysed the allelic usage of the two alternative PEG1/MEST transcripts encoding isoforms 1 and 2, separately. In addition, expression levels of the two transcripts have been measured by real-time RT-PCR, in order to elucidate the mechanism behind the switch from monoallelic transcription in normal breast tissue to biallelic expression in invasive cancer. The isoform 1 transcript is imprinted in both the paired normal tissue and the breast carcinomas. In contrast, the isoform 2 transcript is biallelically expressed, or in one case expressed from the opposite allele to isoform 1, raising the possibility that isoform 2 is polymorphically imprinted in normal breast tissue. In all the paired normal samples, isoform 1 is predominantly expressed, explaining the monoallelic profiles of these samples. However, in four of the seven biallelic carcinomas, isoform 2 is expressed at higher levels than isoform 1, indicating that a switch in expression from isoform 1 to isoform 2 is responsible for the biallelic profiles in these samples. Our results not only suggest a novel mechanism leading to biallelic expression detected when analysing the common 3'-UTR of the PEG1/MEST transcriptional unit, they are also indicative of the existence of further alternative PEG1/MEST transcripts.