The transition of the Polish real estate market within a Central and Eastern European context

The real estate market in Poland is a relatively immature market, but one that has been experiencing substantial transformation. The development of the market has been encouraged by a number of factors, including changes arising as a result of new legislation and the migration of capital between capital markets. The progress of the real estate sector towards a western style competitive market has taken place within the gradual transformation of the Polish economy into a free market economy. As investment grade property is in relatively short supply in Poland, investors consider opportunities within the wider CEE block. An analysis of the risk-return characteristics of the three largest CEE real estate markets namely, Poland, Hungary and Czech Republic, shows that the returns in these markets have been negatively correlated with the UK. As these economies and markets evolve, and being part of the wider EU trading block, their economic performance will slowly converge and become more synchronized with their western counterparts. However, the catch-up of the CEE markets to western European performance cycles will be protracted and consequently there are likely to be significant ongoing portfolio risk reduction opportunitie

Heterozygous mis-sense mutations in Prkcb as a critical determinant of anti-polysaccharide antibody formation

To identify rate-limiting steps in T cell-independent type 2 (TI-2) antibody production against polysaccharide antigens, we performed a genome-wide screen by immunizing several hundred pedigrees of C57BL/6 mice segregating ENU-induced mis-sense mutations. Two independent mutations, Tilcara and Untied, were isolated that semi-dominantly diminished antibody against polysaccharide but not protein antigens. Both mutations resulted from single amino acid substitutions within the kinase domain of Protein Kinase C Beta (PKCβ). In Tilcara, a Ser552>Pro mutation occurred in helix G, in close proximity to a docking site for the inhibitory N-terminal pseudosubstrate domain of the enzyme, resulting in almost complete loss of active, autophosphorylated PKCβI whereas the amount of alternatively spliced PKCβII protein was not markedly reduced. Circulating B cell subsets were normal and acute responses to BCR-stimulation such as CD25 induction and initiation of DNA synthesis were only measurably diminished in Tilcara homozygotes, whereas the fraction of cells that had divided multiple times was decreased to an intermediate degree in heterozygotes. These results, coupled with evidence of numerous mis-sense PRKCB mutations in the human genome, identify Prkcb as a genetically sensitive step likely to contribute substantially to population variability in anti-polysaccharide antibody levels

Effects of Age and Functional Status on the Relationship of Systolic Blood Pressure With Mortality in Mid and Late Life: The ARIC Study

Impaired functional status attenuates the relationship of systolic blood pressure (SBP) with mortality in older adults but has not been studied in middle-aged populations

The Transcription co-Repressors MTG8 and MTG16 Regulate Exit of Intestinal Stem Cells From Their Niche and Differentiation into Enterocyte vs Secretory Lineages

BACKGROUND & AIMS: Notch signaling maintains intestinal stem cells (ISCs). When ISCs exit the niche, Notch signaling among early progenitor cells at position +4/5 regulates their specification toward secretory vs enterocyte lineages (binary fate). The transcription factor ATOH1 is repressed by Notch in ISCs; its de-repression, when Notch is inactivated, drives progenitor cells to differentiate along the secretory lineage. However, it is not clear what promotes transition of ISCs to progenitors and how this fate decision is established. METHODS: We sorted cells from Lgr5-Gfp knock-in intestines from mice and characterized gene expression patterns. We analyzed Notch regulation by examining expression profiles (by quantitative reverse transcription PCR and RNAscope) of small intestinal organoids incubated with the Notch inhibitor DAPT, intestine tissues from mice given injections of the γ-secretase inhibitor dibenzazepine, and mice with intestine-specific disruption of Rbpj. We analyzed intestine tissues from mice with disruption of the RUNX1 translocation partner 1 gene (Runx1t1, also called Mtg8) or CBFA2/RUNX1 partner transcriptional co-repressor 3 (Cbfa2t3, also called Mtg16), and derived their organoids, by histology, immunohistochemistry, and RNA sequencing. We performed chromatin immunoprecipitation and sequencing analyses of intestinal crypts to identify genes regulated by MTG16. RESULTS: The transcription co-repressors MTG8 and MTG16 were highly expressed by +4/5 early progenitors, compared with other cells along crypt-villus axis. Expression of MTG8 and MTG16 were repressed by Notch signaling via ATOH1 in organoids and intestine tissues from mice. MTG8- and MTG16-knockout intestines had increased crypt hyperproliferation and expansion of ISCs, but enterocyte differentiation was impaired, based on loss of enterocyte markers and functions. Chromatin immunoprecipitation and sequencing analyses showed that MTG16 bound to promoters of genes that are specifically expressed by stem cells (such as Lgr5 and Ascl2) and repressed their transcription. MTG16 also bound to previously reported enhancer regions of genes regulated by ATOH1, including genes that encode delta-like canonical Notch ligand and other secretory-specific transcription factors. CONCLUSIONS: In intestine tissues of mice and human intestinal organoids, MTG8 and MTG16 repress transcription in the earliest progenitor cells to promote exit of ISCs from their niche (niche exit) and control the binary fate decision (secretory vs enterocyte lineage) by repressing genes regulated by ATOH1

Orthostatic Hypotension in Middle-Age and Risk of Falls

One-third of older adults fall each year. Orthostatic hypotension (OH) has been hypothesized as an important risk factor for falls, but findings from prior studies have been inconsistent

Operationalizing Frailty in the Atherosclerosis Risk in Communities Study Cohort

Background: Factors that may contribute to the development of frailty in late life have not been widely investigated. The Atherosclerosis Risk in Communities (ARIC) Study cohort presents an opportunity to examine relationships of midlife risk factors with frailty in late life. However, we first present findings on the validation of an established frailty phenotype in this predominantly biracial population of older adults. Methods: Among 6,080 participants, we defined frailty based upon the Cardiovascular Health Study (CHS) criteria incorporating measures of weight loss, exhaustion, slow walking speed, low physical activity, and low grip strength. Criterion and predictive validity of the frailty phenotype were estimated from associations between frailty status and participants' physical and mental health status, physiologic markers, and incident clinical outcomes. Results: A total of 393 (6.5%) participants were classified as frail and 50.4% pre-frail, similar to CHS (6.9% frail, 46.6% pre-frail). In age-adjusted analyses, frailty was concurrently associated with depressive symptoms, low self-rated health, low medication adherence, and clinical biomarker levels (ie, cholesterol, hemoglobin A1c, white blood cell count, C-reactive protein, and hemoglobin). During 1-year follow-up, frailty was associated with falls, low physical ability, fatigue, and mortality. Conclusions: These findings support the validity of the CHS frailty phenotype in the ARIC Study cohort. Future studies in ARIC may elucidate early-life exposures that contribute to late-life frailty

Spousal influence on physical activity in middle-aged and older adults

Low physical activity levels are a public health concern. Few studies have assessed the concordance of physical activity change among spouses. We studied this concordance during a 6-year period (baseline: 1987-1989; follow-up: 1993-1995) in 3,261 spousal pairs from the US-based Atherosclerosis Risk in Communities (ARIC) Study. Linear regression was used to examine the association between change in individuals' sport/exercise and leisure physical activity indices (ranging from 1 (low) to 5 (high)) and change in his or her spouse's indices. The association between individual and spousal changes in meeting physical activity recommendations was assessed with logistic regression. Individual changes in the sport/exercise and leisure indices were positively associated with spousal changes. For every standard deviation increase in their wives' sport/exercise index, men's exercise index increased by 0.09 (95% confidence interval: 0.05, 0.12) standard deviation; for every standard deviation increase in their wives' leisure index, men's leisure index increased by 0.08 standard deviation. Results were similar for women. Individuals had higher odds of meeting physical activity recommendations if their spouse met recommendations at both visits or just follow-up. In conclusion, changes in an individual's physical activity are positively associated with changes in his or her spouse's physical activity. Physical activity promotion efforts should consider targeting couples

Protrusion of the carotid canal into the sphenoid sinuses: evaluation before endonasal endoscopic sinus surgery

Background: Many reports have previously indicated the vast number of anatomical variations of the sphenoid sinuses, e.g. presence of the recesses. Notwithstanding, there are a few crucial neurovascular structures directly neighbouring with the sinuses. The following research aimed to evaluate frequency prevalence of the carotid canal’s protrusion into the sphenoid sinuses in adult population.Materials and methods: Computed tomography (CT) scans of the paranasal sinuses of 296 patients (147 females, 149 males) were analysed in this retrospective study. The patients did not present any pathology in the sinuses. Spiral CT scanner Siemens Somatom Sensation 16 was used in the standard procedure in the option Siemens CARE Dose 4D.Results: Protrusion of the carotid canal was found in the majority of the patients — 55.74%, more frequently in males (65.1% of the patients) than in females (46.26% of the patients). The said variant — regardless of gender — was noted more often bilaterally (41.55% of the cases: 29.93% females, 53.02% males) than unilaterally (14.19% of the cases: 16.33% females, 12.08% males). In the unilateral type (regardless of gender), the protrusion was more common for the left sphenoid sinus — 10.81% of the patients (12.24% females, 9.4% males) than for the right — 3.38% of the patients (4.08% females, 2.68% males).Conclusions: Complicated structure of the paranasal sinuses, derived from the high prevalence of their anatomical variations, may perplex routine surgical interventions. Henceforth, referral for a CT scan is imperative in order to abate the risks associated with an invasive procedure in the said region