Dynamic equations for a fully anisotropic elastic plate

A hierarchy of dynamic plate equations is derived for a fully anisotropic elastic plate. Using power series expansions in the thickness coordinate for the displacement components, recursion relations are obtained among the expansion functions. Adopting these in the boundary conditions on the plate surfaces and along the edges, a set of dynamic equations with pertinent edge boundary conditions are derived on implicit form. These can be truncated to any order and are believed to be asymptotically correct. For the special case of an orthotropic plate, explicit plate equations are presented and compared analytically and numerically to other approximate theories given in the literature. These results show that the present theory capture the plate behavior accurately concerning dispersion curves, eigenfrequencies as well as stress and displacement distributions

Mortality after surgery for benign prostate hyperplasia : a nationwide cohort study

Purpose To investigate postoperative mortality rates and risk factors for mortality after surgical treatment of benign prostate hyperplasia (BPH). Methods All patients who underwent partial prostate excision/resection from 2004 to 2014 in Finland were retrospectively assessed for eligibility using a nationwide registry. Procedures were classified as transurethral resection of the prostate (TURP), laser vaporization of the prostate (laser), and open prostatectomy. Univariable and multivariable regression were used to analyze the association of age, Charlson comorbidity index (CCI), operation type, annual center operation volume, study era, atrial fibrillation, and prostate cancer diagnosis with 90 days postoperative mortality. Results Among the 39,320 patients, TURP was the most common operation type for lower urinary tract symptoms in all age groups. The overall 90 days postoperative mortality was 1.10%. Excess mortality in the 90 days postoperative period was less than 0.5% in all age groups. Postoperative mortality after laser operations was 0.59% and 1.16% after TURP (p = 0.035). Older age, CCI score, and atrial fibrillation were identified as risk factors for postoperative mortality. Prostate cancer diagnosis and the center's annual operation volume were not significantly associated with mortality. The most common underlying causes of death were malignancy (35.5%) and cardiac disease (30.9%). Conclusion Elective urologic procedures for BPH are generally considered safe, but mortality increases with age. Laser operations may be associated with lower mortality rates than the gold standard TURP. Thus, operative risks and benefits must be carefully considered on a case-by-case basis. Further studies comparing operation types are needed.Peer reviewe

Vascular endothelium plays a key role in directing pulmonary epithelial cell differentiation.

The vascular endothelium is critical for induction of appropriate lineage differentiation in organogenesis. In this study, we report that dysfunctional pulmonary endothelium, resulting from the loss of matrix Gla protein (MGP), causes ectopic hepatic differentiation in the pulmonary epithelium. We demonstrate uncontrolled induction of the hepatic growth factor (HGF) caused by dysregulated cross talk between pulmonary endothelium and epithelium in Mgp-null lungs. Elevated HGF induced hepatocyte nuclear factor 4 α (Hnf4a), which competed with NK2 homeobox 1 (Nkx2.1) for binding to forkhead box A2 (Foxa2) to drive hepatic differentiation in Mgp-null airway progenitor cells. Limiting endothelial HGF reduced Hnf4a, abolished interference of Hnf4a with Foxa2, and reduced hepatic differentiation in Mgp-null lungs. Together, our results suggest that endothelial-epithelial interactions, maintained by MGP, are essential in pulmonary cell differentiation

Prognostic and predictive value of ALDH1, SOX2 and SSEA-4 in bladder cancer

Transurethral resection of bladder tumor (TUR-BT) and radical cystectomy (RC) are standard treatment options for bladder cancer (BC). Neoadjuvant chemotherapy (NAC) prior to RC improves outcome of some patients but currently there are no valid biomarkers to identify patients who benefit from NAC. Presence of cancer stem cells (CSC) has been associated with poor outcome and resistance to chemotherapy in various cancers. Here we studied the expression of stem cell markers ALDH1, SOX2 and SSEA-4 with immunohistochemistry in tissue microarray material consisting of 195 BC patients treated with RC and 74 patients treated with TUR-BT followed by NAC and RC. Post-operative follow-up data of up to 22 years was used. Negative to weak cytoplasmic SOX2 staining was associated with lymphovascular invasion and non-organ confined disease. It was also associated with shortened cancer-specific survival, but the finding was not statistically significant. Contrary to previous reports, none of the other tested biomarkers were associated with cancer-specific mortality or clinicopathological characteristics. Neither were they associated with response to NAC. Despite the promising results of previously published studies, our results suggest that CSC markers ALDH1, SOX2 and SSEA-4 have little if any prognostic or predictive value in BC treated with RC.Peer reviewe

Noggin depletion in adipocytes promotes obesity in mice.

ObjectiveObesity has increased to pandemic levels and enhanced understanding of adipose regulation is required for new treatment strategies. Although bone morphogenetic proteins (BMPs) influence adipogenesis, the effect of BMP antagonists such as Noggin is largely unknown. The aim of the study was to define the role of Noggin, an extracellular BMP inhibitor, in adipogenesis.MethodsWe generated adipose-derived progenitor cells and a mouse model with adipocyte-specific Noggin deletion using the AdiponectinCre transgenic mouse, and determined the adipose phenotype of Noggin-deficiency.ResultsOur studies showed that Noggin is expressed in progenitor cells but declines in adipocytes, possibly allowing for lipid accumulation. Correspondingly, adipocyte-specific Noggin deletion in vivo promoted age-related obesity in both genders with no change in food intake. Although the loss of Noggin caused white adipose tissue hypertrophy, and whitening and impaired function in brown adipose tissue in both genders, there were clear gender differences with the females being most affected. The females had suppressed expression of brown adipose markers and thermogenic genes including peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1alpha) and uncoupling protein 1 (UCP1) as well as genes associated with adipogenesis and lipid metabolism. The males, on the other hand, had early changes in a few BAT markers and thermogenic genes, but the main changes were in the genes associated with adipogenesis and lipid metabolism. Further characterization revealed that both genders had reductions in VO2, VCO2, and RER, whereas females also had reduced heat production. Noggin was also reduced in diet-induced obesity in inbred mice consistent with the obesity phenotype of the Noggin-deficient mice.ConclusionsBMP signaling regulates female and male adipogenesis through different metabolic pathways. Modulation of adipose tissue metabolism by select BMP antagonists may be a strategy for long-term regulation of age-related weight gain and obesity

Prediction of neo-adjuvant chemotherapy response in bladder cancer : the impact of clinical parameters and routine biomarkers

Purpose To investigate the role of clinical parameters and immunohistochemical (IHC) biomarkers in their feasibility to predict the effect of neo-adjuvant chemotherapy (NAC) in patients with muscle-invasive urothelial bladder cancer (MIBC). Materials and methods The first 76 consecutive patients with MIBC treated with NAC and radical cystectomy in two University hospitals in Finland between 2008 and 2013 were chosen for this study. After excluding patients with non-urothelial cancer, less than two cycles of chemotherapy, no tissue material for IHC analysis or non-muscle-invasive bladder cancer in re-review, 59 patients were included in the final analysis. A tissue microarray block was constructed from the transurethral resection samples and IHC stainings of Ki-67, p53, Her-2 and EGFR were made. The correlations between histological features in transurethral resection samples and immune-histochemical stainings were calculated. The associations of clinicopathological parameters and IHC stainings with NAC response were evaluated. Factors affecting survival were estimated. Results The complete response rate after NAC was 44%. A higher number of chemotherapy cycles was associated with better response to neo-adjuvant chemotherapy. No response to neo-adjuvant chemotherapy and female gender was associated with decreased cancer-specific survival. The IHC stainings used failed to show an association with neo-adjuvant chemotherapy response and overall or cancer specific survival. Conclusions Patients who do not respond to neo-adjuvant chemotherapy do significantly worse than responders. This study could not find clinical tools to distinguish responders from non-responders. Further studies preferably with larger cohorts addressing this issue are warranted to improve the selection of patients for neo-adjuvant chemotherapy.Peer reviewe

Ablaatiohoidot - sädehoidon jälkeen paikallisesti uusiutuneen eturauhassyövän hoitovaihtoehto

Uusien kuvantamismenetelmien myötä eturauhassyövän paikantaminen ja riskiluokitus ovat tarkentuneet. Magneettikuvauksella pystytään usein luotettavasti visualisoimaan ennusteen kannalta merkittävin syöpäkasvain. Modernit kuvantamisohjatut ablatiiviset eli kudosta tuhoavat hoitomenetelmät kohdistuvat hoidettavaan elimeen niin, että pyritään välttämään ympäröivien kudosten vaurioita. Koko rauhasen käsittäviin ablaatiohoitoihin vaikuttaa liittyvän suotuisampi haittavaikutusprofiili kuin leikkaukseen ja sädehoitoon. Primaarikasvaimeen kohdistuvassa hoidossa eli rauhasen osan hoitostrategiassa (fokaaliterapia) elämänlaadulliset haitat näyttävät edelleen vähentyvän ilman, että tehossa olisi merkittävästi eroa koko rauhasen hoitoihin verrattuna. Tieteellinen näyttö koko rauhasen ja rauhasen osan ablaatiohoitojen pitkäaikaistehosta paikallisen eturauhassyövän hoidossa on toistaiseksi niukkaa, ja ablaatio- ja standardihoitoja vertailevat tutkimukset puuttuvat. Sen sijaan sädehoidon jälkeen paikallisesti uusiutuneen eturauhassyövän ablatiiviset hoitomenetelmät tuovat uuden tehokkaan hoidon tähän vaativaan kliiniseen ongelmaan

Mortality after surgery for benign prostate hyperplasia: a nationwide cohort study

PurposeTo investigate postoperative mortality rates and risk factors for mortality after surgical treatment of benign prostate hyperplasia (BPH).MethodsAll patients who underwent partial prostate excision/resection from 2004 to 2014 in Finland were retrospectively assessed for eligibility using a nationwide registry. Procedures were classified as transurethral resection of the prostate (TURP), laser vaporization of the prostate (laser), and open prostatectomy. Univariable and multivariable regression were used to analyze the association of age, Charlson comorbidity index (CCI), operation type, annual center operation volume, study era, atrial fibrillation, and prostate cancer diagnosis with 90 days postoperative mortality.ResultsAmong the 39,320 patients, TURP was the most common operation type for lower urinary tract symptoms in all age groups. The overall 90 days postoperative mortality was 1.10%. Excess mortality in the 90 days postoperative period was less than 0.5% in all age groups. Postoperative mortality after laser operations was 0.59% and 1.16% after TURP (p = 0.035). Older age, CCI score, and atrial fibrillation were identified as risk factors for postoperative mortality. Prostate cancer diagnosis and the center's annual operation volume were not significantly associated with mortality. The most common underlying causes of death were malignancy (35.5%) and cardiac disease (30.9%). ConclusionElective urologic procedures for BPH are generally considered safe, but mortality increases with age. Laser operations may be associated with lower mortality rates than the gold standard TURP. Thus, operative risks and benefits must be carefully considered on a case-by-case basis. Further studies comparing operation types are needed.</p