Feasibility of Lifestyle Redesign® for community-dwelling older adults with and without disabilities: Results from an exploratory descriptive qualitative clinical research design.

INTRODUCTION: Although Lifestyle Redesign® has been shown to be effective in improving older adults' health and well-being, little is known about the feasibility of implementing this programme to develop meaningful and health-promoting routines of community-dwelling older adults in Canada. This study thus aimed to explore the feasibility of implementing a culturally-adapted 6-month version of Lifestyle Redesign® with community-dwelling older French-Canadians with and without disabilities. METHODS: An exploratory descriptive qualitative clinical research design was used with 17 older adults living at home or in a seniors' residence, divided into two groups participating in Lifestyle Redesign®. Semi-structured interviews were conducted with participants and the occupational therapist who delivered the programme and recorded clinical notes. FINDINGS: Participants were aged between 65 and 90; they were mainly women (n = 11; 64.7%), and seven (41.2%) had disabilities. The intervention was tailored to the participants' needs, interests, and capacities in each group (e.g. modules selected, number of individual sessions, and assistance of volunteer). Over the 6-month period, older adults participated in an average of about 25 group sessions with the occupational therapist and in four or five outings with their group (e.g. restaurant, market, and museum) and attended between 5 and 11 individual sessions with the occupational therapist. The most common reasons for missing group sessions were being ill, working, or having another appointment. Personal facilitators and barriers to participation in the intervention were mainly related to abilities, needs, spiritual life, and health. Environmental facilitators were mostly the regularity of the sessions, group, and external support, including human resources to deliver the intervention, whereas barriers were the residence's time restrictions and staff's attitudes, cost of some activities targeted in the programme, and transportation problems. CONCLUSION: Lifestyle Redesign® is a feasible preventive occupational therapy intervention for community-dwelling older French-Canadians. These findings will guide future studies including large-scale clinical trials.

Tracking and predicting COVID-19 radiological trajectory on chest X-rays using deep learning.

Radiological findings on chest X-ray (CXR) have shown to be essential for the proper management of COVID-19 patients as the maximum severity over the course of the disease is closely linked to the outcome. As such, evaluation of future severity from current CXR would be highly desirable. We trained a repurposed deep learning algorithm on the CheXnet open dataset (224,316 chest X-ray images of 65,240 unique patients) to extract features that mapped to radiological labels. We collected CXRs of COVID-19-positive patients from an open-source dataset (COVID-19 image data collection) and from a multi-institutional local ICU dataset. The data was grouped into pairs of sequential CXRs and were categorized into three categories: 'Worse', 'Stable', or 'Improved' on the basis of radiological evolution ascertained from images and reports. Classical machine-learning algorithms were trained on the deep learning extracted features to perform immediate severity evaluation and prediction of future radiological trajectory. Receiver operating characteristic analyses and Mann-Whitney tests were performed. Deep learning predictions between "Worse" and "Improved" outcome categories and for severity stratification were significantly different for three radiological signs and one diagnostic ('Consolidation', 'Lung Lesion', 'Pleural effusion' and 'Pneumonia'; all P < 0.05). Features from the first CXR of each pair could correctly predict the outcome category between 'Worse' and 'Improved' cases with a 0.81 (0.74-0.83 95% CI) AUC in the open-access dataset and with a 0.66 (0.67-0.64 95% CI) AUC in the ICU dataset. Features extracted from the CXR could predict disease severity with a 52.3% accuracy in a 4-way classification. Severity evaluation trained on the COVID-19 image data collection had good out-of-distribution generalization when testing on the local dataset, with 81.6% of intubated ICU patients being classified as critically ill, and the predicted severity was correlated with the clinical outcome with a 0.639 AUC. CXR deep learning features show promise for classifying disease severity and trajectory. Once validated in studies incorporating clinical data and with larger sample sizes, this information may be considered to inform triage decisions.

Deep learning of chest X-rays can predict mechanical ventilation outcome in ICU-admitted COVID-19 patients.

The COVID-19 pandemic repeatedly overwhelms healthcare systems capacity and forced the development and implementation of triage guidelines in ICU for scarce resources (e.g. mechanical ventilation). These guidelines were often based on known risk factors for COVID-19. It is proposed that image data, specifically bedside computed X-ray (CXR), provide additional predictive information on mortality following mechanical ventilation that can be incorporated in the guidelines. Deep transfer learning was used to extract convolutional features from a systematically collected, multi-institutional dataset of COVID-19 ICU patients. A model predicting outcome of mechanical ventilation (remission or mortality) was trained on the extracted features and compared to a model based on known, aggregated risk factors. The model reached a 0.702 area under the curve (95% CI 0.707-0.694) at predicting mechanical ventilation outcome from pre-intubation CXRs, higher than the risk factor model. Combining imaging data and risk factors increased model performance to 0.743 AUC (95% CI 0.746-0.732). Additionally, a post-hoc analysis showed an increase performance on high-quality than low-quality CXRs, suggesting that using only high-quality images would result in an even stronger model.

Cause determination of missed lung nodules and impact of reader training and education: Simulation study with nodule insertion software.

BACKGROUND: There are "blind spots" on chest computed tomography (CT) where pulmonary nodules can easily be overlooked. The number of missed pulmonary nodules can be minimized by instituting a training program with particular focus on the depiction of nodules at blind spots. PURPOSE: The purpose of this study was to assess the variation in lung nodule detection in chest CT based on location, attenuation characteristics, and reader experience. MATERIALS AND METHODS: We selected 18 noncalcified lung nodules (6-8 mm) suspicious of primary and metastatic lung cancer with solid (n = 7), pure ground-glass (6), and part-solid ground-glass (5) attenuation from 12 chest CT scans. These nodules were randomly inserted in chest CT of 34 patients in lung hila, 1st costochondral junction, branching vessels, paramediastinal lungs, lung apices, juxta-diaphragm, and middle and outer thirds of the lungs. Two residents and two chest imaging clinical fellows evaluated the CT images twice, over a 4-month interval. Before the second reading session, the readers were trained and made aware of the potential blind spots. Chi-square test was used to assess statistical significance. RESULTS: Pretraining session: Fellows detected significantly more part-solid ground-glass nodules compared to residents (P = 0.008). A substantial number of nodules adjacent to branching vessels and posterior mediastinum were missed. Posttraining session: There was a significant increase in detectability independent of attenuation and location of nodules for all readers (P < 0.0008). CONCLUSION: Dedicated chest CT training improves detection of lung nodules, especially the part-solid ground-glass nodules. Detection of nodules adjacent to branching vessels and the posterior mediastinal lungs is difficult even for fellowship-trained radiologists.

[Lifestyle Redesign® (Remodeler sa vie): First Pilot Study Among Older French-Canadians]. / Remodeler sa vie® (Lifestyle Redesign) : première étude pilote auprès d'aînés franco-canadiens.

DESCRIPTION.: Recently translated and adapted to the French-Canadian context, the program Remodeler sa vie (Lifestyle Redesign) aims to develop meaningful and healthy lifestyle. The influence of this newly adapted program on older French-Canadians was, however, unknown. OBJECTIVE.: The aim of this study was to describe the influence of the Remodeler sa vie on older French-Canadians' life balance, engagement in meaningful activities, self-compassion and gratitude. METHOD.: A mixed-method design (preexperimental and qualitative clinical) was used in a pilot study with 16 participants distributed in two groups (with and without disabilities). Pre- and post-intervention questionnaires as well as semi-structured interviews were completed. RESULTS.: An increase of life-balance in all participants (p = .03) and of engagement in meaningful activities in older adults without disability (p = .02) was observed. The participants also reported improvements for all outcomes. CONCLUSION.: Remodeler sa vie is a culturally promising program to promote health among older French-Canadians.

DESCRIPTION.: Récemment traduit et adapté au contexte franco-canadien, le programme Remodeler sa vie (Lifestyle Redesign) vise le développement de modes de vie sains et porteurs de sens. On connaît toutefois peu l'influence de ce programme chez les aînés francophones. BUT.: Décrire l'influence du programme Remodeler sa vie sur l'équilibre de vie, l'engagement dans les activités signifiantes, la compassion et la gratitude d'aînés franco-canadiens. MÉTHODOLOGIE.: Une étude pilote mixte (préexpérimental et qualitatif clinique) a été réalisée auprès de 16 aînés répartis en deux groupes (avec et sans incapacités). Des questionnaires pré et post-intervention ainsi que des entretiens semi-dirigés ont été complétés. RÉSULTATS.: Une augmentation de l'équilibre de vie de l'ensemble participants (p = 0,03) et de l'engagement dans des activités signifiantes des aînés sans incapacité (p = 0,02) a été observée. Les participants rapportaient des améliorations pour l'ensemble des résultantes. CONSÉQUENCES.: Remodeler sa vie est un programme prometteur pour promouvoir la santé des aînés franco-canadiens.

Transcatheter aortic valve replacement with the balloon-expandable SAPIEN 3 valve: Impact of calcium score on valve performance and clinical outcomes.

BACKGROUND: Aortic valve calcification severity has been associated with higher rates of aortic regurgitation (AR) following TAVR, but scarce data exist on its impact with the use of newer generation transcatheter heart valves. METHODS: This was a multicenter study including 626 patients with severe aortic stenosis who underwent TAVR with the SAPIEN 3 valve. Patients were divided in 2 groups according to the median index calcium score (iCS) for each sex: high CS (HCS, iCS ≥ median), and low iCS (LCS, iCS < median). Another analysis was performed in those patients with extreme iCS (ECS, iCS >75th percentile for each sex). Clinical and echocardiographic data were collected prospectively in a dedicated database. RESULTS: The mean CS was 3758 ±â€¯1417 AU and 1616 ±â€¯691 AU in the HCS and LCS groups, respectively (p < 0.001). There were no differences between groups in 30-day mortality (HCS:2.6%, LCS:1.0%, p = 0.13) and stroke (HCS:2.6%,LCS:2.6%, p = 1.0) rates, but all cases (n = 5) of annulus rupture occurred in the HCS group (1.6% vs. 0%, p = 0.061). The incidence of moderate-severe AR post-TAVR was low in both groups (HCS:1.6%,LCS:1.6%, p = 1.0), and valve gradient and area were similar between groups. The results remained similar in the ECS group (mean CS:4607 ±â€¯1424 AU), but a mildly increased mean transvalvular gradient post-TAVR was observed in ECS patients (12.1 ±â€¯5.6 vs 11.0 ±â€¯4.3 mmHg; p = 0.015). CONCLUSION: Aortic valve calcification severity failed to impact mortality/stroke rates following TAVR with the SAPIEN 3 valve. Low rates of significant AR were observed irrespective of CS, and a mild increase in transvalvular gradient was observed in ECS patients.

Development and Validation of Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia Diagnostic Criteria.

INTRODUCTION: Diffuse idiopathic pulmonary neuroendocrine hyperplasia (DIPNECH) is a rare condition that is likely underdiagnosed owing to the lack of established and validated diagnostic criteria. These clinical guidelines are empirical and created on the basis of a limited number of studies. This study was designed to validate the existing criteria and to identify new clinical parameters that can accurately diagnose DIPNECH. METHODS: Patients with DIPNECH were identified from a cohort that underwent surgical lung resection for pulmonary carcinoids. The study cohort included a total of 105 consecutive cases with neuroendocrine lesions. Initial diagnostic predictors of DIPNECH were selected from the literature. We employed univariate and multivariate models to evaluate the association of clinical, pathologic, radiologic variables with the likelihood of DIPNECH. RESULTS: Univariate analysis identified age, sex, chronic obstructive pulmonary disease diagnosis, obstructive abnormalities, pulmonary nodules, mosaicism, absolute numbers of pulmonary neuroendocrine lesions (PNELs), and the number of tumorlets as significant DIPNECH predictors (for p < 0.05). After adjustment for sampling variations, the ratio of the total number of PNELs to the number of bronchioles was found to be considerably higher in DIPNECH category. Multivariate analysis identified the total number of PNELs and multiple pulmonary nodules (>10) as independent predictors of DIPNECH. The performance of our criteria revealed an accuracy of 76% in detecting DIPNECH cases. CONCLUSIONS: We proposed a set of diagnostic criteria for DIPNECH on the basis of an expert-panel approach integrating pathological features, radiology, and clinical data. Our findings will help identify DIPNECH patients, without a pathological confirmation of a neuroendocrine lesion. Before the implementation of these criteria in clinical practice, they require further validation in multi-institutional cohorts.

Influence of Lifestyle Redesign® on Health, Social Participation, Leisure, and Mobility of Older French-Canadians.

IMPORTANCE: Developed in California to enable community-dwelling older adults to maintain healthy and meaningful activities, Lifestyle Redesign® is a well-known cost-effective preventive occupational therapy intervention. The impact of a newly adapted French version on older French-Canadians was, however, unknown. OBJECTIVE: To explore the influence of Lifestyle Redesign on older French-Canadians' health, social participation, leisure, and mobility. DESIGN: A mixed-methods design included a preexperimental component (questionnaires administered before and after the intervention and 3 and 6 mo postintervention) and an exploratory descriptive qualitative clinical study. Individual semidirected interviews were digitally audiotaped and transcribed, then underwent thematic content analysis using mix extraction grids. SETTING: Community. PARTICIPANTS: Sixteen volunteers (10 women) aged 65-90 yr (mean = 76.4, standard deviation = 7.6), 10 without and 6 with disabilities. Inclusion criteria were age ≥65 yr, normal cognitive functions, residence in a conventional or senior home, and French speaking. INTERVENTION: French-Canadian 6-mo version of Lifestyle Redesign. OUTCOMES AND MEASURES: Health, social participation, leisure, and mobility were measured using the 36-item Short Form Health Survey, Social Participation Scale, Leisure Profile, and Life-Space Assessment, as well as a semistructured interview guide. RESULTS: The French-Canadian Lifestyle Redesign had a beneficial effect on participants' mental health (p = .02) and interest in leisure (p = .02) and, in those with disabilities, social participation (p = .03) and attitudes toward leisure (p = .04). Participants reported positive effects on their mental health, leisure, mobility, and social participation, including frequency and quality of social interactions, and indicated that having an occupational routine fostered better health. None of the participants reported no effect. CONCLUSION AND RELEVANCE: The translated and culturally adapted Lifestyle Redesign is a promising occupational therapy intervention for community-dwelling older French-Canadians. WHAT THIS ARTICLE ADDS: This study sheds light on the influence of the French-Canadian version of the intervention not only on older adults' health and social participation but also on their leisure activities and life-space mobility, two important outcomes not addressed in previous Lifestyle Redesign studies. Moreover, this study provides an in-depth understanding of the Lifestyle Redesign experience of French-Canadian older adults with and without disabilities, including participants with significant communication and mobility disabilities.

Early-onset emphysema in a large French-Canadian family: a genetic investigation.

BACKGROUND: Inherited mutations in SERPINA1 coding for the alpha-1 antitrypsin (A1AT) protein is the only well established cause of hereditary emphysema. We aimed to identify the genetic ecause of early-onset emphysema in a five-generation French-Canadian family free of A1AT deficiency. METHODS: Between Dec 1, 2014, and April 1, 2017, we investigated 63 individuals from a single pedigree, including 55 with DNA available. Whole-exome sequencing was done in a convenience sample of 14 individuals (nine with unambiguous expression of the typical form of emphysema observed in this family). We filtered rare non-synonymous variants that were predicted to be damaging to identify a single mutation in a biologically relevant gene shared among all affected individuals. We assessed segregation with the disease in additional family members who were not evaluated by whole-exome sequencing. The effect of the candidate variant on protein function was evaluated in vitro. mRNA and protein expression of the candidate gene was assessed in lung samples from unrelated individuals (n=80) with and without emphysema who underwent surgery for lung cancer at our institution. FINDINGS: A rare in-silico-predicted damaging variant (Ala455Thr) was identified in the protein tyrosine phosphatase non-receptor type 6 (PTPN6) gene, also known as SHP-1, an important negative regulator of immune processes. 20 (95%) of 21 family members with computed tomography-confirmed emphysema were heterozygotes for the Ala455Thr mutation. No Thr455 homozygotes were identified. Emphysema or reduced diffusion capacity was observed in all heterozygotes with a history of smoking. Incomplete penetrance of the mutation and variable degrees of emphysema were observed in never smokers. The Ala455Thr mutation in SHP-1 caused a reduction in phosphatase activity in vitro, confirming the loss-of-function effect of the mutation. mRNA and protein expression of PTPN6 were upregulated in smokers, but were not associated with emphysema or severity of airflow limitation. INTERPRETATION: An inherited variant in the gene PTPN6 is responsible for early-onset emphysema in this family. To our knowledge, this is the second form of hereditary emphysema since the discovery of A1AT deficiency in the 1960s, representing a breakthrough in understanding the genetics and pathogenesis of emphysema. FUNDING: Fonds sur les maladies respiratoires J.-D. Bégin-P.-H. Lavoie de l'Université Laval, Fondation de l'Institut universitaire de cardiologie et de pneumologie de Québec, CIHR/GSK research Chair on COPD at Université Laval, and the Canadian Institutes of Health Research.

[Effects of Lifestyle Redesign on older adults: A systematic review]. / Effets du Lifestyle Redesign chez les aînés : une recension systématique.

BACKGROUND.: The Lifestyle Redesign® (LR) aims to support health, functioning, and quality of life of older adults through the development of healthy and meaningful routines. However, evidence concerning the effectiveness and cost-effectiveness of this intervention is scattered. PURPOSE.: This study aimed to synthetize the clinical effects and cost-effectiveness of the LR as well as to verify the applicability of the results in a community-based setting in Quebec. METHOD.: A systematic review of the literature was conducted, followed by a focus group with four occupational therapists. FINDINGS.: Considered as cost-effective (under $50,000 in quality-adjusted life-years), the LR offers benefits for both mental and physical health. According to occupational therapists, the LR is clearly relevant for their practice but involves some challenges. IMPLICATIONS.: The LR is an occupational therapy intervention with promising clinical effects and cost-effectiveness for older adults living in the community.

DESCRIPTION.: Le Lifestyle Redesign® (LR) a pour objectif de soutenir, à travers des routines occupationnelles saines et signifiantes, la santé, le fonctionnement et la qualité de vie d'aînés. Les données probantes concernant son efficacité et sa rentabilité sont toutefois dispersées. BUT.: Cette étude visait à synthétiser les effets cliniques et le coût-efficacité du LR et à vérifier l'applicabilité des résultats en milieu communautaire québécois. MÉTHODOLOGIE.: Une recension systématique des écrits a été réalisée, suivie d'un groupe de discussion auprès de quatre ergothérapeutes. RÉSULTATS.: Considéré rentable (sous les 50 000 $ d'année de vie ajustée par la qualité), le LR présente des bénéfices tant pour la santé mentale que physique. Selon les ergothérapeutes consultés, la pertinence d'intégrer le LR à leur pratique est sans équivoque, mais comporte des défis. CONSÉQUENCES.: Le LR est une intervention ergothérapique dont les effets cliniques et le coût-efficacité sont prometteurs pour les aînés vivant dans la communauté.

Buttocks Hard as Rocks: Not Wanted after Aortic Dissection Repair.

The authors report the case of a patient developing a gluteal compartment syndrome after DeBakey type I dissection repair. Prompt recognition and treatment led to successful results. The surgical approach to the gluteal compartment is described.

Mitral Annular Calcification and Mitral Valve Replacement: A New Approach.

Mitral valve replacement is technically challenging in the context of mitral annular calcification. A new surgical strategy is described that was used in a 71-year-old obese patient, where intraatrial prosthesis insertion and valve fixation into native uncalcified structures were performed without calcium debridement.

Primary Paratracheal Leiomyoma: Increased Preoperative Diagnostic Specificity With Magnetic Resonance Imaging.

We report the case of a 47-year-old woman whose primary mediastinal leiomyoma was incidentally found during evaluation of her persistent cough. The preoperative diagnosis of mediastinal leiomyoma is challenging because of its rarity and indeterminate features on chest radiography, computed tomography (CT), and positron emission tomography-CT. We highlight how magnetic resonance imaging can substantially contribute to mediastinal mass characterization and diagnostic specificity.

Diffuse Parenchymal Abnormalities in Acutely Dyspneic Patients: A Pattern-based Approach.

Acute dyspnea is a common presenting complaint in the Emergency Room. Evaluation with chest radiography is vital for initial assessment and may reveal diffuse parenchymal abnormalities that require further assessment with computed tomography (CT). The aim of this review is to outline a pattern-based approach for the analysis of diffuse pulmonary abnormalities in an acutely dyspneic patient with emphasis on CT appearances. Specific disease entities may be differentiated by their distribution in the lungs and by their radiologic findings. Recognition of the predominant finding and its distribution can generate an appropriate differential diagnosis that is further refined by the presence or absence of ancillary findings. Incorporation of the clinical history, laboratory data, and prior studies narrows the differential diagnosis, indicates the optimum modality for further evaluation, and, in some situations, provides important prognostic data.

Androgen receptor as a potential sign of prostate cancer metastasis.

BACKGROUND: Androgen receptor (AR) expression and its modulation through the carcinogenesis process have been investigated in several studies with conflicting results. MATERIALS AND METHODS: In situ hybridization and immunocytochemistry were used to examine AR expression in prostatic needle core biopsies of benign, high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma. RESULTS: A significant increase in AR mRNA levels was found in the cancerous prostatic cells when compared with the benign tissue biopsies. AR abundance in HGPIN was found to be almost half-way between that observed in benign and in cancerous tissue. In the benign prostatic epithelium, the immunocytochemistry data show that AR is exclusively expressed in the nuclei of epithelial cells. However, in 72% of examined cancer biopsies, AR was expressed in both the cytoplasm and nuclei. After examination of medical records of 100 patients diagnosed with prostate cancer, it was found that the AR was expressed in both cellular compartments of cancer cells in 81% of cases when cancer was found to have metastasized outside the prostate. In contrast, when the cancer was organ-confined, AR was localized in both the nuclei and cytoplasm in only 66% of cases. Moreover, when the AR was expressed in the cytoplasm of cancerous cells, consecutive serial sections immunostained with the mitochondrial marker suggest that AR is localized in the mitochondria. CONCLUSIONS: AR mRNA expression is significantly higher in prostate cancer when compared to benign prostatic tissue.

Assessment of PARP-3 distribution in tissues of cynomolgous monkeys.

Poly(ADP-ribose) polymerase 3 (PARP-3) is a newly characterized PARP. In contrast to the two best-studied nuclear PARPs, PARP-1 and PARP-2, PARP-3 activity is apparently not stimulated by DNA damage. However, our previous work has demonstrated that PARP-3 interacts with several DNA damage response proteins, including Ku70/Ku80, DNA-PK, and PARP-1, suggesting that it contributes to the DNA damage response. Furthermore, a possible function for PARP-3 in the regulation of gene expression has been inferred from our observations that it associates with polycomb group proteins, which are responsible for epigenetic modifications leading to gene silencing. In this report, we extend our characterization of PARP-3 by revealing its distribution in the tissues and cell types of adult cynomolgous monkeys using a well-characterized PARP-3 polyclonal antibody. This study is the first to demonstrate that PARP-3 is genuinely expressed in most of the examined tissues. However, its expression is highly restricted to specific cell types of each tissue, indicating that PARP-3 expression is tightly regulated. One of the key findings of this study is that PARP-3 is highly expressed in the nuclei of epithelial cells forming the ducts of prostate, salivary glands, liver, and pancreas and in the neurons of terminal ganglia.

Evaluation of AIbZIP and Cdc47 as markers for human prostatic diseases.

OBJECTIVES: Benign prostatic hyperplasia and prostate cancer are important public health issues. However, histologic markers for these diseases are limited. METHODS: Immunocytochemistry was used to analyze the cellular localization of AIbZIP, Cdc47, androgen receptor and estrogen receptor-beta markers. AIbZIP is a protein recently found to be more abundant in prostate cancer than in benign prostatic tissue, and Cdc47 is a cell proliferation-associated protein. The localization and modulation of androgen receptor and estrogen receptor-beta through the carcinogenesis process have been examined in several studies but controversial results were obtained. These four proteins were evaluated as potential markers of prostatic diseases in 210 needle core biopsies, including normal prostate, benign prostatic hyperplasia, low-grade and high-grade prostatic intraepithelial neoplasia, and different Gleason grades of prostatic adenocarcinoma. RESULTS: Androgen receptor and estrogen receptor-beta do not discriminate between benign and malignant specimens, while AIbZIP was able to distinguish between them. Cdc47, in contrast, discriminated not only between malignant and benign prostatic tissue, but also between benign prostatic hyperplasia and normal prostatic tissue. CONCLUSIONS: Cdc47 appears to be a sensitive marker of prostatic diseases since its expression gradually increased in parallel with the severity of the lesion. AIbZIP discriminated between benign tissue and cancer. AIbZIP and Cdc47 thus appear to be useful markers with diagnostic and prognostic values.

Expression of enzymes involved in estrogen metabolism in human prostate.

There is evidence that estrogens can directly modulate human prostate cell activity. It has also been shown that cultured human prostate cancer LNCaP can synthesize the active estrogen estradiol (E2). To elucidate the metabolism of estrogens in the human prostate, we have studied the expression of enzymes involved in the formation and inactivation of estrogens at the cellular level. 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) types 1, 2, 4, 7, and 12, as well as aromatase mRNA and protein expressions, were studied in benign prostatic hyperplasia (BPH) specimens using in situ hybridization and immunohistochemistry. For 17beta-HSD type 4, only in situ hybridization studies were performed. Identical results were obtained with in situ hybridization and immunohistochemistry. All the enzymes studied were shown to be expressed in both epithelial and stromal cells, with the exception of 17beta-HSD types 4 and 7, which were detected only in the epithelial cells. On the basis of our previous results, showing that 3beta-HSD and 17beta-HSD type 5 are expressed in human prostate, and of the present data, it can be concluded that the human prostate expresses all the enzymes involved in the conversion of circulating dehydroepiandrosterone (DHEA) to E2. The local biosynthesis of E2 might be involved in the development and/or progression of prostate pathology such as BPH and prostate cancer through modulation of estrogen receptors, which are also expressed in epithelial and stromal cells.

Tetrahydrogestrinone induces a genomic signature typical of a potent anabolic steroid.

Tetrahydrogestrinone (THG) is a recently identified compound having the greatest impact in the world of sports. In order to obtain a highly accurate and sensitive assessment of the potential anabolic/androgenic activity of THG, we have used microarrays to identify its effect on the expression of practically all the 30,000 genes in the mouse genome and compared it with the effect of dihydrotestosterone (DHT), the most potent natural androgen. Quite remarkably, we found that 671 of the genes modulated by THG in the mouse muscle levator ani are modulated in a similar fashion by DHT, while in the gastrocnemius muscle and prostate, 95 and 939 genes respectively, are modulated in common by the two steroids. On the other hand, THG is more potent than DHT in binding to the androgen receptor, while, under in vivo conditions, THG possesses 20% of the potency of DHT in stimulating prostate, seminal vesicle and levator ani muscle weight in the mouse. The present microarray data provide an extremely precise and unquestionable signature of the androgenic/anabolic activity of THG, an approach which should apply to the analysis of the activity of any anabolic steroid.