Are cash incentives always king? A randomized controlled trial evaluating hedonic versus cash incentives (TEH-C).

Introduction: Physical inactivity is a risk factor for obesity and non-communicable diseases. Despite myriad health and non-health benefits resulting from physical activity (PA), most individuals do not meet PA recommendations. Providing an incentive for meeting activity goals may increase activity levels. Classical economists argue that cash is the best incentive. Behavioral economists have posited that hedonic (pleasurable) incentives (e.g., massages, restaurant meals) may be superior to cash when incentives are offered over multiple time periods. To date, no studies have directly compared the effectiveness of cash versus hedonic incentives in promoting PA across multiple time periods. Methods: We conducted a two-arm, parallel, 4-month randomized controlled trial with healthy adults in Singapore where participants were randomized to either cash or hedonic incentives. Participants could earn up to SGD50 (≈USD37) in cash or hedonic incentives each month they met the study's step target of 10,000 steps daily on at least 20/25 days out of the first 28 days of a month. The primary objective was to compare the mean proportion of months that participants met the step target between the two arms. Results: By month 4, participants in the cash (N = 154) and hedonic incentive (N = 156) arms increased their mean daily steps by 870 (p < 0.001) and 1,000 steps (p < 0.001), respectively. The mean proportion of months the step target was achieved was 90.53 and 88.34 for participants in the cash and hedonic incentive arms respectively, but differences across arms were small and not statistically significant for this or any outcome assessed. Conclusion: Our findings suggest that both cash and hedonic incentives are effective at promoting physical activity but that neither strategy is clearly superior.Clinical trial registration: ClinicalTrials.gov, NCT04618757 registered on November 6, 2020.

Accustomed to the heat: Temperature and thyroid hormone influences on oogenesis and gonadal steroidogenesis pathways vary among populations of Amargosa pupfish (Cyprinodon nevadensis amargosae).

Many fish experience diminished reproductive performance under atypically high or prolonged elevations of temperature. Such high temperature inhibition of reproduction comes about in part from altered stimulation of gametogenesis by the hypothalamic-pituitary-gonadal (HPG) endocrine axis. Elevated temperatures have also been shown to affect thyroid hormone (TH) signaling, and altered TH status under high temperatures may impact gametogenesis via crosstalk with HPG axis pathways. Here, we examined effects of temperature and 3'-triiodo-L-thyronine (T3) on pathways for gonadal steroidogenesis and gametogenesis in Amargosa pupfish (Cyprinodon nevadensis amargosae) from two allopatric populations: 1) the Amargosa River - a highly variable temperature habitat, and 2) Tecopa Bore - an invariably warm groundwater-fed marsh. These populations were previously shown to differ in TH signaling profiles both in the wild and under common laboratory conditions. Sexually-mature pupfish from each population were maintained at 24 °C or 34 °C for 88 days, after which a subset of fish was treated with T3 for 18-24 h. In both populations, mRNA abundances for follicle-stimulating hormone receptor and luteinizing hormone receptor were higher in the ovary and testis at 24 °C compared to 34 °C. Females from Tecopa Bore - but not from the Amargosa River - also had greater ovarian transcript abundances for steroidogenic enzymes cytochrome P450 aromatase, 3ß-hydroxysteroid dehydrogenase, and 17ß-hydroxysteroid dehydrogenase at 24 °C compared to 34 °C, as well as higher liver mRNA levels of vitellogenins and choriogenins at cooler temperature. Transcript abundances for estrogen receptors esr1, esr2a, and esr2b were reduced at 34 °C in Amargosa River females, but not in Tecopa Bore females. T3 augmented gonadal gene transcript levels for steroid acute regulatory protein (StAR) transporter in both sexes and populations. T3 also downregulated liver estrogen receptor mRNAs in females from the warmer Tecopa Bore habitat only, suggesting T3 modulation of liver E2 sensitivity as a possible mechanism whereby temperature-induced changes in TH status may contribute to shifts in thermal sensitivity for oogenesis.

Widespread alterations to hypothalamic-pituitary-gonadal (HPG) axis signaling underlie high temperature reproductive inhibition in the eurythermal sheepshead minnow (Cyprinodon variegatus).

Fish experiencing abnormally high or prolonged elevations in temperature can exhibit impaired reproduction, even for species adapted to warm water environments. Such high temperature inhibition of reproduction has been linked to diminished gonadal steroidogenesis, but the mechanisms whereby hypothalamic-pituitary-gonadal (HPG) axis signaling is impacted by high temperature are not fully understood. Here, we characterized differences in HPG status in adult sheepshead minnow (Cyprinodon variegatus), a eurythermal salt marsh and estuarine species of eastern North America, exposed for 14 d to temperatures of 27 °C or 37 °C. Males and females at 37 °C had lower gonadosomatic index (GSI) values compared to fish at 27 °C, and females at 37 °C had fewer spawning capable eggs and lower circulating 17ß-estradiol (E2). Gene transcripts encoding gonadotropin-inhibitory hormone (gnih) and gonadotropin-releasing hormone-3 (gnrh3) were higher in relative abundance in the hypothalamus of both sexes at 37 °C. While pituitary mRNAs for the ß-subunits of follicle-stimulating hormone (fshß) and luteinizing hormone (lhß) were lowered only in males at 37 °C, Fsh and Lh receptor mRNA levels in the gonads were at lower relative levels in both the ovary and testis of fish at 37 °C. Females at 37 °C also showed reduced ovarian mRNA levels for steroid acute regulatory protein (star), P450 side-chain cleavage enzyme (cyp11a1), 3ß-hydroxysteroid dehydrogenase (3ßhsd), 17ß-hydroxysteroid dehydrogenase (hsd17ß3), and ovarian aromatase (cyp19a1a). Females at the higher 37 °C temperature also had a lower liver expression of mRNAs encoding estrogen receptor α (esr1) and several vitellogenin and choriogenin genes, but elevated mRNA levels for hepatic sex hormone-binding globulin (shbg). Our results substantiate prior findings that exposure of fish to high temperature can inhibit gonadal steroidogenesis and oogenesis, and point to declines in reproductive performance emerging from alterations at several levels of HPG axis signaling including increased hypothalamic Gnih expression, depressed gonadal steroidogenesis, and reduced egg yolk and egg envelope protein production in the liver.

Report on influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza in 2018.

As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 3993 human influenza-positive samples during 2018. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or hens' eggs for use as potential seasonal influenza vaccine virus candidates. In 2018, influenza A(H1)pdm09 viruses predominated over influenza A(H3) and B viruses, accounting for a total of 53% of all viruses analysed. The majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO-recommended vaccine strains for the Southern Hemisphere in 2018. However, phylogenetic analysis indicated that a significant proportion of circulating A(H3) viruses had undergone genetic drift relative to the WHO-recommended vaccine strain for 2018. Of 2864 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, three A(H1)pdm09 viruses showed highly reduced inhibition by oseltamivir, while one B/Victoria virus showed highly reduced inhibition by both oseltamivir and zanamivir.

An urban stormwater runoff mortality syndrome in juvenile coho salmon.

Untreated urban runoff poses significant water quality threats to aquatic organisms. In northwestern North America, ongoing development in coastal watersheds is increasing the transport of toxic chemical contaminants to river and stream networks that provide spawning and rearing habitats for several species of Pacific salmon. Adult coho (Oncorhynchus kisutch) are particularly vulnerable to a stormwater-driven mortality syndrome. The phenomenon may prematurely kill more than half of the coho that return each fall to spawn in catchments with a high degree of imperviousness. Here we evaluate the coho mortality syndrome at the juvenile life stage. Freshwater-stage juveniles were exposed to stormwater collected from a high traffic volume urban arterial roadway. Symptoms characteristic of the mortality syndrome were evaluated using digital image analysis, and discrete stages of abnormal behavior were characterized as the syndrome progressed. At a subset of these stages, blood was analyzed for ion homeostasis, hematocrit, pH, glucose, and lactate. Several of these blood chemistry parameters were significantly dysregulated in symptomatic juvenile coho. Affected fish did not recover when transferred to clean water, suggesting a single runoff event to stream habitats could be lethal if resident coho become overtly symptomatic. Among coho life stages, our findings indicate the urban runoff mortality syndrome is not unique to adult spawners. Therefore, the consequences for wild coho populations in developing watersheds are likely to be greater than previously anticipated.

Capture and Control: Working Memory Modulates Attentional Capture by Reward-Related Stimuli.

Physically salient but task-irrelevant distractors can capture attention in visual search, but resource-dependent, executive-control processes can help reduce this distraction. However, it is not only physically salient stimuli that grab our attention: Recent research has shown that reward history also influences the likelihood that stimuli will capture attention. Here, we investigated whether resource-dependent control processes modulate the effect of reward on attentional capture, much as for the effect of physical salience. To this end, we used eye tracking with a rewarded visual search task and compared performance under conditions of high and low working memory load. In two experiments, we demonstrated that oculomotor capture by high-reward distractor stimuli is enhanced under high memory load. These results highlight the role of executive-control processes in modulating distraction by reward-related stimuli. Our findings have implications for understanding the neurocognitive processes involved in real-life conditions in which reward-related stimuli may influence behavior, such as addiction.

Report on influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza in 2017

As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a record total of 5866 human influenza positive samples during 2017. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties and were propagated in qualified cells and hens' eggs for use as potential seasonal influenza vaccine virus candidates. In 2017, influenza A(H3) viruses predominated over influenza A(H1)pdm09 and B viruses, accounting for a total of 54% of all viruses analysed. The majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2017. However, phylogenetic analysis indicated that the majority of circulating A(H3) viruses had undergone genetic drift relative to the WHO recommended vaccine strain for 2017. Of 3733 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, only two A(H1)pdm09 viruses and one A(H3) virus showed highly reduced inhibition by oseltamivir, while just one A(H1)pdm09 virus showed highly reduced inhibition by zanamivir.

Annual report on influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza in 2016

As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 4,247 human influenza positive samples during 2016. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties and also propagated in qualified cells and hens eggs for potential seasonal influenza vaccine virus candidates. In 2016, influenza A(H3) viruses predominated over influenza A(H1)pdm09 and B viruses, accounting for a total of 51% of all viruses analysed. The vast majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2016. However, phylogenetic analysis of a selection of viruses indicated that the majority of circulating A(H3) viruses had undergone some genetic drift relative to the WHO recommended strain for 2016. Of more than 3,000 samples tested for resistance to the neuraminidase inhibitors oseltamivir and zanamivir, six A(H1)pdm09 viruses and two B/Victoria lineage viruses showed highly reduced inhibition to oseltamivir.

Interspecies variation in the susceptibility of adult Pacific salmon to toxic urban stormwater runoff.

Adult coho salmon (Oncorhynchus kisutch) prematurely die when they return from the ocean to spawn in urban watersheds throughout northwestern North America. The available evidence suggests the annual mortality events are caused by toxic stormwater runoff. The underlying pathophysiology of the urban spawner mortality syndrome is not known, and it is unclear whether closely related species of Pacific salmon are similarly at risk. The present study co-exposed adult coho and chum (O. keta) salmon to runoff from a high traffic volume urban arterial roadway. The spawners were monitored for the familiar symptoms of the mortality syndrome, including surface swimming, loss of orientation, and loss of equilibrium. Moreover, the hematology of both species was profiled by measuring arterial pH, blood gases, lactate, plasma electrolytes, hematocrit, and glucose. Adult coho developed behavioral symptoms within a few hours of exposure to stormwater. Various measured hematological parameters were significantly altered compared to coho controls, indicating a blood acidosis and ionoregulatory disturbance. By contrast, runoff-exposed chum spawners showed essentially no indications of the mortality syndrome, and measured blood hematological parameters were similar to unexposed chum controls. We conclude that contaminant(s) in urban runoff are the likely cause of the disruption of ion balance and pH in coho but not chum salmon. Among the thousands of chemicals in stormwater, future forensic analyses should focus on the gill or cardiovascular system of coho salmon. Because of their distinctive sensitivity to urban runoff, adult coho remain an important vertebrate indicator species for degraded water quality in freshwater habitats under pressure from human population growth and urbanization.

Influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza annual report, 2015.

As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System, the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 5,557 influenza positive samples during 2015. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties. In 2015, influenza B viruses predominated over influenza A(H1)pdm09 and A(H3) viruses, accounting for a total of 58% of all viruses analysed. The vast majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2015. However, phylogenetic analysis of a selection of viruses indicated that the majority of circulating A(H3) viruses were genetically distinct from the WHO recommended strain for 2015, resulting in an update to the recommended vaccine strain for the Southern Hemisphere for 2016. With an increasing predominance of B/Victoria lineage viruses over B/Yamagata lineage viruses through the course of 2015, WHO also updated the recommended influenza B strain in the trivalent influenza vaccine for 2016. Of more than 3,300 samples tested for resistance to the neuraminidase inhibitors oseltamivir and zanamivir, only 1 A(H1)pdm09 virus showed highly reduced inhibition by oseltamivir. The Centre undertook primary isolation of candidate vaccine viruses directly into eggs, and in 2015 a total of 45 viruses were successfully isolated in eggs.

Tianshengyuan-1 (TSY-1) regulates cellular Telomerase activity by methylation of TERT promoter.

Telomere and Telomerase have recently been explored as anti-aging and anti-cancer drug targets with only limited success. Previously we showed that the Chinese herbal medicine Tianshengyuan-1 (TSY-1), an agent used to treat bone marrow deficiency, has a profound effect on stimulating Telomerase activity in hematopoietic cells. Here, the mechanism of TSY-1 on cellular Telomerase activity was further investigated using HL60, a promyelocytic leukemia cell line, normal peripheral blood mononuclear cells, and CD34+ hematopoietic stem cells derived from umbilical cord blood. TSY-1 increases Telomerase activity in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells with innately low Telomerase activity but decreases Telomerase activity in HL60 cells with high intrinsic Telomerase activity, both in a dose-response manner. Gene profiling analysis identified Telomerase reverse transcriptase (TERT) as the potential target gene associated with the TSY-1 effect, which was verified by both RT-PCR and western blot analysis. The ß-galactosidase reporter staining assay showed that the effect of TSY-1 on Telomerase activity correlates with cell senescence. TSY-1 induced hypomethylation within TERT core promoter in HL60 cells but induced hypermethylation within TERT core promoter in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells. TSY-1 appears to affect the Telomerase activity in different cell lines differently and the effect is associated with TERT expression, possibly via the methylation of TERT promoter.

Endocrine and metabolic impacts of warming aquatic habitats: differential responses between recently isolated populations of a eurythermal desert pupfish.

Temperatures of inland aquatic habitats are increasing with climate change, and understanding how fishes respond physiologically to thermal stress will be crucial for identifying species most susceptible to these changes. Desert fishes may be particularly vulnerable to rising temperatures because many species occupy only a fraction of their historical range and occur in habitats with already high temperatures. Here, we examined endocrine and metabolic responses to elevated temperature in Amargosa pupfish, Cyprinodon nevadensis amargosae. We studied C. n. amargosae from two habitats with distinct thermal conditions: the Amargosa River, which experiences diurnally and seasonally variable temperatures (0.2-40°C); and Tecopa Bore, a spring and marsh fed by hot groundwater (47.5°C) from an artesian borehole. These allopatric populations differ in morphology, and prior evidence suggests that temperature might contribute to these differences via altered thyroid hormone (TH) regulation of morphological development. Here, we document variation in hepatic iodothyronine deiodinase type 2 (dio2) and type 3 (dio3) and TH receptor ß (trß) gene transcript abundance between the Amargosa River and Tecopa Bore wild populations. Fish from these populations acclimated to 24 or 34°C retained differences in hepatic dio2, dio3 and trß mRNAs and also varied in transcripts encoding the TH membrane transporters monocarboxylate transporter 8 (mct8) and organic anion-transporting protein 1c1 (oatp1c1). Tecopa Bore pupfish also exhibited higher dio2 and trß mRNA levels in skeletal muscle relative to Amargosa River fish. Muscle citrate synthase activity was lower at 34°C for both populations, whereas lactate dehydrogenase activity and lactate dehydrogenase A-chain (ldhA) transcripts were both higher and 3,5,3'-triiodothryonine responsive in Tecopa Bore pupfish only. These findings reveal that local population variation and thermal experience interact to shape how pupfish respond to elevated temperatures, and point to the need to consider such interactions in management actions for desert fishes under a changing climate.

Influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza annual report, 2014.

The WHO Collaborating Centre for Reference and Research on Influenza in Melbourne is part of the World Health Organization's (WHO) Global Influenza Surveillance and Response System. In 2014 the Centre received a total of 5,374 influenza samples from laboratories primarily in the Asia-Pacific region. Viruses were characterised by their antigenic, genetic and antiviral drug resistance properties. Of the viruses successfully analysed 52% were A(H1N1)pdm09 viruses. The majority of these were antigenically and genetically similar to the WHO recommended reference strain for the 2014 Southern Hemisphere influenza vaccine. Results for A(H3N2) and B/Yamagata viruses suggested that circulating viruses of this subtype and lineage, respectively, had undergone antigenic and/or genetic changes, consistent with the decision by WHO to change recommended strains for the 2015 Southern Hemisphere vaccine. A small number of A(H1N1)pdm09 and B/Victoria viruses had highly reduced inhibition to the neuraminidase inhibitors oseltamivir and zanamivir. The Centre also undertook primary isolation of vaccine candidate viruses directly into eggs. A total of 38 viruses were successfully isolated in eggs, of which 1 (B/Phuket/3073/2013) was included in the 2015 Southern Hemisphere influenza vaccine.

Indicators of success: academic research partnerships to implement performance indicator systems in Clubhouses.

TOPIC: This article describes a collaboration between academic researchers and Clubhouses to develop and implement a statewide Clubhouse performance indicator system. PURPOSE: Given the challenging funding climate, it is important that Clubhouses are able to gather service provision and performance data. However, establishing the necessary data structures can be a daunting task, and partnerships with academic researchers can aid in this process. We detail one such collaboration, utilizing a participatory research public-academic liaison framework, between researchers and Hawai'i's Clubhouses. SOURCES USED: Sources used include published literature, personal communication, and personal observation. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Lessons learned during the collaboration include the importance of face-to-face contact, technology training, duplicated and unduplicated variables, and tailoring data structures to the culture and work-ordered day of each Clubhouse. Experiences in this collaboration confirm that with support Clubhouse members are capable of fulfilling the rigorous responsibilities of contributing to a performance indicator system.

Recurrent exophytic meningioma in pregnancy.

BACKGROUND: Meningiomas are slow-growing tumors that may present in pregnancy because of accelerated growth. We present the case of a recurrent meningioma in two separate pregnancies in the same woman. CASE: A 35-year-old woman presented at 30 weeks of gestation with limb weakness, vomiting, and a progressive decreased level of consciousness with an enlarging forehead mass. Imaging revealed a massive extra-axial exophytic tumor. An emergency craniotomy was performed, complicated by massive blood loss. Final pathology showed a grade I meningioma positive for progesterone receptors. Maternal-fetal outcome was good, with return of normal neurologic status and elective delivery at 38 weeks of gestation. CONCLUSION: Pregnancy is associated with accelerated meningioma growth and recurrence. Treatment during pregnancy is possible and requires a multidisciplinary approach.

Analysis of 120 pediatric patients with nonmalignant disorders transplanted using unrelated plasma-depleted or -reduced cord blood.

BACKGROUND: Unrelated cord blood (CB) is an important stem cell source for unrelated hematopoietic cell transplantation (HCT) of patients with nonmalignant disorders. Processing methods to prepare red blood cell-reduced CB units incur significant nucleated cell loss. In contrast, plasma depletion or reduction (PDR) processing of CB units entails the removal of only a portion of the plasma with minimal nucleated cell loss. However, there are relatively limited data regarding outcomes of CB transplants using units processed by PDR. STUDY DESIGN AND METHODS: A Center for International Blood and Marrow Transplant Research (CIBMTR)-audited analysis was performed on 120 pediatric patients with nonmalignant disorders transplanted between November 2001 and January 2008 at 29 US and 17 international centers using PDR CB units from two CB banks. RESULTS: Transplant characteristics were as follows: median age, 3.5 years (range, 0.1-14 years); median patient weight, 15 kg (range, 4-61 kg); 58% male; HLA matches (intermediate-resolution HLA-A and HLA-B and high-resolution HLA-DRB1) of the units used in these patients six of six in 26, five of six in 48, four of six in 47, and three of six or two of six in 6; median prefreeze total nucleated cell dose, 10.5×10(7)/kg; median prefreeze CD34+ dose, 3.7×10(5)/kg; and nonmyeloablative regimen in 24%. The median times to myeloid and platelet engraftment were 21 and 49 days, respectively. The cumulative incidence of reported Grade II to IV acute graft-versus-host disease (aGVHD) was 38±5%, and 19±4% had Grade III to IV aGVHD. The Kaplan-Meier estimates of 3-year transplant-related mortality, overall survival, and disease-free survival were 20±4, 79±4, and 70±6%, respectively. CONCLUSION: These data demonstrate the effectiveness of PDR CB units for HCT.

Cell recovery comparison between plasma depletion/reduction- and red cell reduction-processing of umbilical cord blood.

BACKGROUND AIMS: Limited cell dose has hampered the use of cord blood transplantation (CBT) in adults. One method of minimizing nucleated cell loss in cord blood (CB) processing is to deplete or reduce plasma but not red blood cells - plasma depletion/reduction (PDR). METHODS: The nucleated cell loss of PDR was studied, and determined to be less than 0.1% in the discarded supernatant plasma fraction in validation experiments. After testing and archival sampling, the median nucleated cell recovery for PDR processing was 90%, and median CD34(+) cell recovery 88%. In a CB bank inventory of 12 339 products with both pre- and post-processing total nucleated cells (TNC), PDR processing resulted in median post-processing TNC recoveries of 90.0% after testing and archival samples removal. Using the same 10 CB units divided into two halves, we compared directly the recovery of PDR against hydroxyethyl starch red cell reduction (RCR) for TNC, CD34(+) cells and colony-forming units (CFU-GM, CFU-E, CFU-GEMM and total CFU) after parallel processing. We also compared the loss of very small embryonic-like stem cells (VSEL). RESULTS: We demonstrated significantly higher recoveries using PDR for TNC (124%), CD34(+) cells (121%), CFU-GM (225%), CFU-GEMM (201%), total CFU (186%) and VSEL (187%). The proportion of high TNC products was compared between 10 912 PDR and 38 819 RCR CB products and found to be 200% higher for products that had TNC ≥150 × 10(7) (P = 0.0001) for the PDR inventory. CONCLUSIONS: Our data indicate that PDR processing of CB provides a significantly more efficient usage of this valuable and scarce resource.

Identification and characterization of repopulating spermatogonial stem cells from the adult human testis.

BACKGROUND: This study was conducted to identify and characterize repopulating spermatogonial stem cells (SSCs) in the adult human testes. METHODS: Testes biopsies from obstructive azoospermic patients and normal segments of human testicular tissue were used. Flow cytometry, real-time PCR and immunohistochemical analysis were performed. Purified human spermatogonia were transplanted into busulfan-treated recipient mouse testes and integrated cells were detected by human nuclear protein antibody co-localized with stem cell and germ cell markers. RESULTS: Testicular biopsies collected from obstructive azoospermic men showed similar morphology and distribution of markers to the normal human testes. Flow cytometry showed distinct populations of stage-specific embryonic antigen-4 (SSEA-4), CD49f and CD90 positive cells in the adult human testes. SSEA-4 (+) cells showed high expression levels of SSC-specific genes and high levels of telomerase activity. Extensive colonization of human cells in the mouse testes indicates the presence of highly enriched populations of SSCs in the SSEA-4 (+) sorted cells. All the HNP (+) cells in the mouse testes were positive for germ cell marker dead box mRNA helicase and only half of them were dimly positive for c-kit. In addition, subpopulations of human spermatogonia that colonized mouse testes were positively stained for CD49f, GPR-125, Nanog and Oct-4 indicating the existence of population of cells among human spermatogonia with SSC and pluripotent characteristics. CONCLUSIONS: This study clearly demonstrates that repopulating human SSCs have phenotypic characteristics of SSEA-4(+), CD49f(+), GPR-125(+)and c-Kit (neg/low). The results have direct implications for enrichment of human spermatogonia for further culture and germ cell differentiation studies.

Expression and organization of basement membranes and focal adhesion proteins in pregnant myometrium is regulated by uterine stretch.

The mechanisms underlying the preparation of the uterus for labor are not fully understood. We have previously found a significant increase in the expression of messenger RNA (mRNAs) encoding extracellular basement membrane (BM) proteins of the smooth muscle cells (SMCs) in late pregnant rat myometrium. At term, the myometrium is stretched by growing fetuses and these mechanical signals are transmitted from extracellular matrix into SMCs through focal adhesions (FA). The aim of this study was to investigate the effect of gravidity on the expression and spatiotemporal distribution of major BM proteins, laminin-gamma2 and collagen IV, as well as typical FA constituents, vinculin and paxillin, in the myometrium during gestation and parturition, using a unilaterally pregnant rat model. We found that the expression of laminin-gamma2 and collagen IV proteins increased significantly with gestational age (P < .05) and was dependent on gravidity whereas vinculin and paxillin proteins were not affected. Near term, BM proteins from gravid horn myometrium demonstrated increased extracellular immunostaining and major rearrangement from sporadic protein distribution to organized, continuous, and regular structures surrounding the plasma membrane of each myocyte. Examination of FA proteins revealed that paxillin was translocated from the cytoplasm to the cell periphery, while vinculin was sequestered specifically to FAs. At labor, BM and FA proteins, organized in similar bead-like structures, were localized on opposing sides of SMC plasma membrane into 2 different compartments. We suggest that these stretch-induced changes facilitate formation of stable cell-matrix adhesions and provide the molecular basis for optimal force transduction during labor contractions.

Cardiovascular disease risk among the poor and homeless - what we know so far.

Homelessness [and poverty] is rapidly escalating across North America and is associated with dire implications for public health and our health care systems. Both are compelling states of existence affecting all ages, ethnicities and both genders. Homelessness frequently evolves through a complex interaction of factors that are both internal and external to the individual themselves. Once homeless, equitable access to both preventative and remedial health care is lacking and is associated with a higher than average burden of cardiovascular disease [CVD] risk factors, morbidity and mortality and is accompanied by disproportionately high health care costs. The emergence of limited, small scale programs aimed at addressing the unique health and social needs of the homeless is encouraging. However, there has been inadequate commitment at the National, State or Provincial and local levels to implement policies and dedicate funding and resources to the expansion of such "individual level" interventions into comprehensive programs that deliver sustainable, integrated prevention and services, especially with regard to CVD. The long-term solutions that address the links between homelessness and CVD lie in preventing homelessness and reversing the trends in our health care system that create disparities for lower socioeconomic status [SES] and homeless individuals.