The function of microRNAs in cartilage and osteoarthritis.

MicroRNAs are small double-stranded RNAs, which negatively regulate gene expression and have been shown to have key roles in both chondrocyte development and cartilage homeostasis with age. Deletion of all microRNAs in chondrocytes leads to skeletal growth defects in mice, whilst deletion of specific microRNAs, e.g. miR-140, leads to premature articular cartilage degradation and increased susceptibility to posttraumatic osteoarthritis. Studies comparing microRNA expression in normal human articular cartilage compared to osteoarthritic cartilage show differential expression, but varying sample groups make interpretation difficult. MicroRNAs have been proposed as circulating biomarkers of osteoarthritis, but again, this differs amongst patient cohorts. Many micro-RNAs have been shown to have roles in chondrocyte phenotype via signalling pathways, apoptosis, autophagy and senescence. Modulating microRNAs in the joint has been shown to reduce osteoarthritis in animal models and translating this to man as a novel therapeutic strategy will be key.

Continuous daily sunitinib for recurrent glioblastoma.

Bevacizumab ((BEV) has become a mainstay of treating recurrent glioblastoma, but eventual tumor resistance is expected. Targeting multiple growth-associated signaling pathways may result in more effective treatment than targeting VEGF alone. Patients with recurrent glioblastoma were stratified by prior BEV exposure and treated with sunitinib 37.5 mg daily in this phase II study. Response evaluations were performed at baseline and at the end of every 4 week cycle. Six-month progression-free survival (PFS6) was the primary endpoint for both arms of the study. Secondary endpoints included health related quality of life measures and FDG-PET correlatives with patient outcomes. Sixty-three patients were accrued to this study; thirty-two were BEV-naïve, 31 were BEV-resistant. PFS6 was 10.4 % [95 % CI 3.2-33.8] in the BEV-naïve cohort and 0 % in the BEV-resistant cohort. Median overall survival was 9.4 months [95 % CI 6.15-21.90] in the BEV-naïve cohort and 4.37 months [95 % CI 3.02-6.21] in the BEV-resistant cohort. 3/29 patients (10 %) of the BEV-naïve, and 0/27 BEV-resistant patients achieved radiographic response. Thrombocytopenia, leukopenia, and neutropenia were the most common drug-associated adverse events and occurred with higher frequency than expected. Sunitinib treatment in BEV-naïve patients did not appear to affect outcomes with subsequent BEV therapy. Continuous daily sunitinib did not prolong progression-free survival in BEV-naïve nor BEV-resistant patients with recurrent glioblastoma.

Effect of beta-alanine, with and without sodium bicarbonate, on 2000-m rowing performance.

PURPOSE: To examine the effect of beta-alanine only and beta-alanine with sodium bicarbonate supplementation on 2,000-m rowing performance. METHODS: Twenty well-trained rowers (age 23 ± 4 y; height 1.85 ± 0.08 m; body mass 82.5 ± 8.9 kg) were assigned to either a placebo or beta-alanine (6.4 g · d(-1) for 4 weeks) group. A 2,000-m rowing time trial (TT) was performed before supplementation (Baseline) and after 28 and 30 days of supplementation. The post supplementation trials involved supplementation with either maltodextrin or sodium bicarbonate in a double-blind, crossover design, creating four study conditions (placebo with maltodextrin; placebo with sodium bicarbonate; beta-alanine with maltodextrin; beta-alanine with sodium bicarbonate). Blood lactate, pH, bicarbonate, and base excess were measured pre-TT, immediately post-TT and at TT+5 min. Performance data were analyzed using magnitude based inferences. RESULTS: Beta-alanine supplementation was very likely to be beneficial to 2,000-m rowing performance (6.4 ± 8.1 s effect compared with placebo), with the effect of sodium bicarbonate having a likely benefit (3.2 ± 8.8 s). There was a small (1.1 ± 5.6 s) but possibly beneficial additional effect when combining chronic beta-alanine supplementation with acute sodium bicarbonate supplementation compared with chronic beta-alanine supplementation alone. Sodium bicarbonate ingestion led to increases in plasma pH, base excess, bicarbonate, and lactate concentrations. CONCLUSIONS: Both chronic beta-alanine and acute sodium bicarbonate supplementation alone had positive effects on 2,000-m rowing performance. The addition of acute sodium bicarbonate to chronic beta-alanine supplementation may further enhance rowing performance.

Lessons learned while implementing mandatory health care-associated infection reporting in New York State.

New York State Public Health Law §2819, requiring the mandatory public reporting of health care-associated infections, was enacted in July 2005. This article describes key provisions in the legislation, New York State health care-associated infection program development, the rationale for selection of the National Healthcare Safety Network for reporting, and lessons learned.

"Blueprint version 2.0": updating public health surveillance for the 21st century.

Rapid changes to the United States public health system challenge the current strategic approach to surveillance. During 2011, the Council of State and Territorial Epidemiologists convened national experts to reassess public health surveillance in the United States and update surveillance strategies that were published in a 1996 report and endorsed by the Council of State and Territorial Epidemiologists. Although surveillance goals, historical influences, and most methods have not changed, surveillance is being transformed by 3 influences: public health information and preparedness as national security issues; new information technologies; and health care reform. Each offers opportunities for surveillance, but each also presents challenges that public health epidemiologists can best meet by rigorously applying surveillance evaluation concepts, engaging in national standardization activities driven by electronic technologies and health care reform, and ensuring an adequately trained epidemiology workforce.

Auditory processing neurons influence song evaluation and strength of mate preference in female songbirds.

Animals use a variety of complex signaling mechanisms to convey an array of information that can be detected by conspecifics and heterospecifics. Receivers of those signals perceive that information and use it to direct their subsequent actions. Thus, communication such as that which occurs between senders and receivers of vocal communication signals can be a powerful model in which to investigate the neural basis of sensory perception and action initiation that underlie decision-making. In this study, we investigated how female songbirds perceive the quality of acoustic signals (songs) performed by males and use that information to express preference for one song among many possible alternatives. We use behavioral measurement of song preference before and after lesion-induced alteration of activity in an auditory processing area (caudal nidopallium, NC) for which we have previously described its interconnections with other auditory areas and downstream reward pathways. Our findings reveal that inactivating NC does not change a female's ability or willingness to perform behavioral indicators of mate choice, nor does it change their ability to identify the songs of individual males. However, lesioning NC does induce a decrease in the strength of song preference for specific males more than others. That decrease does not result in a complete elimination of preference, as female preferences for specific males are still evident but not as strongly expressed after lesioning of NC. Taken together, these data indicate that NC plays a role in a female's strength of preference in song evaluation and mate choice, and activity in NC is an important facet of mate choice.

Characteristics of HIV-infected women and factors associated with HCV seropositivity in the Republic of Georgia.

BACKGROUND: The aim of this study was to describe the extent of the HIV epidemic among women in the Republic of Georgia and to identify factors associated with HCV co-infection in this population. FINDINGS: All women aged ≥18 years who were diagnosed with HIV between 1989 and 2006 were identified through the National HIV/AIDS surveillance database. Medical records were reviewed for demographic characteristics, risk factors and HCV serostatus. A total of 249 women were identified. Only 4% declared injection drug use (IDU); sex work was reported by 9%. Substantial risk factors were identified among the women's sexual partners, nearly 69% of whom were IDUs, 84% were HIV positive and 66% HCV positive. Seventeen percent of women were seropositive for HCV. Factors significantly associated with HCV seropositivity in bivariate analyses among non-IDU women were partner IDU+ [Prevalence ratio (PR): 4.5 (95% CI: 1.4, 14.2)], and partner HCV+ [PR: 7.2 (95% CI: 1.8, 29.5)]. CONCLUSIONS: The HIV epidemic in the Republic of Georgia is closely tied to the IDU community. Evidence-based interventions targeting IDU and partners of IDU are urgently required to halt the spread of the HIV epidemic in the country.

Effective state-based surveillance for multidrug-resistant organisms related to health care-associated infections.

In September 2008, the Council of State and Territorial Epidemiologists and the Centers for Disease Control and Prevention sponsored a meeting of public health and infection-control professionals to address the implementation of surveillance for multidrug-resistant organisms (MDROs)-particularly those related to health care-associated infections. The group discussed the role of health departments and defined goals for future surveillance activities. Participants identified the following main points: (1) surveillance should guide prevention and infection-control activities, (2) an MDRO surveillance system should be adaptable and not organism specific, (3) new systems should utilize and link existing systems, and (4) automated electronic laboratory reporting will be an important component of surveillance but will take time to develop. Current MDRO reporting mandates and surveillance methods vary across states and localities. Health departments that have not already done so should be proactive in determining what type of system, if any, will fit their needs.

Prevalence of and risk factors for hepatitis B and C infection among Mongolian blood donors.

BACKGROUND: Mongolia has one of the highest rates of viral hepatitis infections worldwide yet risk factors have been largely unstudied. This sentinel study of hepatitis infection in Mongolia determined the prevalence of hepatitis B virus surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) among a sample of blood donors and identified demographic and behavioral factors associated with hepatitis infection. STUDY DESIGN AND METHODS: Data were collected by interview from 923 Ministry of Health Blood Center donors between August 2004 and February 2005. The exposure variables collected included donor demographics and health and behavioral risk factors. Bivariate and multivariate analyses assessed the prevalence ratio of hepatitis infection for each exposure. RESULTS: Of 923 donors, 72 tested positive for HBsAg (7.8%; 95% confidence interval [CI], 6.1%-9.7%), 89 donors tested positive for anti-HCV (9.6%; 95% CI, 7.8%-11.5%), and six (0.6%) tested positive for both HBsAg and anti-HCV. Prevalence of HBsAg was highest among donors 18 to 19 years and anti-HCV tended to be most prevalent among those more than 40 years of age. Both pregnancy and alcohol use were associated with seroprevalent anti-HCV. CONCLUSION: This sentinel study of hepatitis prevalence among Mongolian blood donors sheds considerable light on the epidemiology of hepatitis virus infection as well as the sociodemographic and behavioral risk factors associated with infection. Young age (HBsAg) and pregnancy (anti-HCV) were significant risk factors for hepatitis virus infection, indicating that improvements in education, vaccination rates, and general infection control procedures in health care institutions may reduce behavioral and nosocomial transmission.

Participatory research in Northwest Atlanta's Proctor Creek Watershed: Using photovoice to explore environmental health risks at the water's edge.

In this study we used a participatory research method, photovoice, to explore community perceptions about environmental health risks, community assets, and strengths in and around an urban, degraded watershed in Northwest Atlanta, Georgia. This watershed, formed by Proctor Creek, is a focal point for redevelopment and infrastructure investments for years to come. Using a community-based participatory research approach, 10 Proctor Creek residents (watershed researchers), and a university partner, engaged in data collection; participatory data analysis; internal discussions; translation of research findings into watershed restoration, community revitalization, remedial action, and policy solutions; and dissemination of results to fellow watershed residents, stakeholders, and decision makers. We present a conceptual model linking the watershed researchers' understanding of urban policies and practice in the Proctor Creek Watershed to environmental, neighborhood and housing conditions and their influence on health outcomes and quality of life. Engaging community members in defining their own community environmental health challenges and assets yielded the following primary themes: 1) threats to the natural environment, 2) built environment stressors that influence health, 3) blight and divestment of public resources, and 4) hope for the future. Residents' vision for the future of the watershed - a restored creek, revitalized neighborhoods, and restored people - is fueled by a strong connection to history, memory, and sense of place. We demonstrate the value of local knowledge in identifying previously unaddressed environmental health risks in the Proctor Creek Watershed as well as solutions to reduce or eliminate them.

Psychological features of abstinent heroin users before and after rehabilitation in Saint Petersburg, Russia.

OBJECTIVE: The objective of the study was to describe psychological features of abstinent heroin users undergoing rehabilitation in Saint Petersburg, Russia. Study subjects (n = 197) were recruited prospectively at the time of their admission to rehabilitation between March 2010 and May 2011 at 7 inpatient opiate addiction rehabilitation centers in Saint-Petersburg and neighboring regions, Russia. The centers provided varying rehabilitation programs; 6 of them were religious centers. Socio-demographic information and self-reported HIV status were collected. Personality profiles and severity of drug-associated problems were estimated before and after rehabilitation using the Minnesota Multiphasic Personality Inventory 2 (MMPI-2), and the Addiction Severity Index (ASI). RESULTS: Thirty-three (17%) subjects dropped out before completing rehabilitation (non-completers). All subjects (completers and non-completers) had psychopathological personality profiles according to MMPI-2. These profiles were refractory to clinically significant improvement after rehabilitation, although some statistically significant changes toward improvement were observed. ASI scores showed statistically and clinically significant improvements after rehabilitation on all scales. Participants in longer-term versus shorter-term rehabilitation programs showed similar changes in their pre- and post-rehabilitation MMPI-2 and ASI scores. Our results suggest that unmet psychiatric needs should be addressed to potentially improve treatment completion in this population.

The low-density lipoprotein receptor is regulated by estrogen and forms a functional complex with the estrogen-regulated protein ezrin in pituitary GH3 somatolactotropes.

Estrogen regulates the function, growth, and proliferation of lactotropes in the pituitary. We report here that low-density lipoprotein (LDL) receptor (LDLR) gene expression and LDL uptake are strongly up-regulated by estrogen in pituitary somatolactotropic GH(3) cells. The uptake of LDL was significantly inhibited by the F-actin-severing drug, swinholide A, indicating that LDL uptake is dependent on the integrity of the cortical actin cytoskeleton in GH(3) cells. We examined whether the estrogen-inducible cytoskeletal linker protein, ezrin, interacts with the LDLR. The LDLR coimmunoprecipitated with ezrin, and fluorescently labeled LDL bound to regions of the cell membrane that colocalized with the active, phosphorylated form of ezrin (phosphoezrin). Evidence for a functional interaction between ezrin and the LDLR was obtained by transient transfection experiments using ezrin-green fluorescent protein (GFP) expression constructs. We observed that transient transfection of GH(3) cells with an ezrin N terminus-GFP dominant-negative construct prevented the uptake of LDL particles, whereas expression of GFP alone or an ezrin C terminus-GFP construct had no effect on LDL uptake. Transfection with the ezrin N terminus dominant- negative construct had no effect on the endocytosis of transferrin. Thus, estrogen stimulates the expression of ezrin and the LDLR in GH(3) cells, which interact physically and functionally to facilitate the endocytosis of LDL. We propose that the up-regulation and interaction of ezrin and the LDLR serves to augment the delivery of cholesterol and other lipids in support of the hypertrophic and proliferative response of cells to estrogen.

Multiple-year experience in the diagnosis of viral central nervous system infections with a panel of polymerase chain reaction assays for detection of 11 viruses.

BACKGROUND: Polymerase chain reaction (PCR) is becoming more common in diagnostic laboratories. In some instances, its value has been established. In other cases, assays exist, but their beneficial use has not been determined. This article summarizes findings from 3485 patients who underwent testing over a 6-year period in our laboratory. METHODS: A panel of PCR assays was used for the detection of a range of viruses associated with central nervous system (CNS) infections. PCR results were analyzed in conjunction with information about patient age and sex, the time between onset and specimen collection, and other variables. Medical chart review was conducted for 280 patients to gain diagnostic and epidemiologic insight with regard to cases of unresolved encephalitis. RESULTS: A total of 498 PCR-positive samples (14.3%) were detected. Enteroviruses accounted for the largest number (360 [72.3%]) of positive PCR results, followed by herpes simplex virus (76 [15.3%]), varicella-zoster virus (29 [5.82%]), and West Nile virus (WNV) (18 [3.61%]). Of 360 patients who tested positive for enterovirus, only 46 met the Centers for Disease Control and Prevention's encephalitis definition. It resulted in the greatest decrease (87.2%) in positive PCR results. Overall, the PCR positivity rate for specimens collected within 5 days after illness onset was 17.2%, compared with 8.6% for specimens collected > or =6 days after onset. CONCLUSIONS: The value of PCR in the diagnosis of viral infections has been established. PCR is of lower value in the detection of WNV in CNS, compared with serological testing, but is of greater value in the detection of other arboviruses, particularly viruses in the California serogroup. Medical chart reviews indicated that apparent CNS infection resolves in approximately 50% of cases.

Hospitalizations and deaths due to Salmonella infections, FoodNet, 1996-1999.

Nontyphoidal Salmonella causes a higher proportion of food-related deaths annually than any other bacterial pathogen in the United States. We reviewed 4 years (1996-1999) of population-based active surveillance data on laboratory-confirmed Salmonella infections from the Emerging Infections Program's Foodborne Diseases Active Surveillance Network (FoodNet), to determine the rates of hospitalization and death associated with Salmonella infection. Overall, 22% of infected persons were hospitalized, with the highest rate (47%) among persons aged >60 years. Fifty-eight deaths occurred, for an estimated annual incidence of 0.08 deaths/100,000 population. These deaths accounted for 38% of all deaths reported through FoodNet from 1996 through 1999, and they occurred primarily among adults with serious underlying disease. Although Salmonella infection was seldom listed as a cause of death on hospital charts and death certificates, our chart review suggests that Salmonella infection contributed to these deaths.

Disease burden and risk factors for hospitalizations associated with rotavirus infection among children in New York State, 1989 through 2000.

OBJECTIVES: To examine trends in hospitalizations for pediatric diarrhea, ascertain the disease burden and risk factors for hospitalizations associated with rotavirus and assess the accuracy of coding for rotavirus hospitalizations in New York State. METHODS: For 1989 through 2000, data were obtained for all diarrhea-associated hospitalizations in New York State among children 1 month through 4 years of age. Characteristics of patients hospitalized with rotavirus were compared with those for hospitalizations with diarrhea from other causes. Medical charts coded as rotavirus diarrhea were reviewed for patients who were discharged during 1997 to determine whether these diagnoses were supported with laboratory results. RESULTS: Diarrhea was reported as a discharge diagnosis in approximately 13% of all hospitalizations for an annual incidence of 83 per 10 000 children. Viruses were the most common etiologic agents reported. Since 1993, when a rotavirus-specific code was introduced, rotavirus infection was coded for 8.7% of all diarrhea-associated hospitalizations. A total of 136 patients with diarrhea died during their hospitalization (hospital fatality rate, 1.6 per 1000), and the 12 deaths among patients with rotavirus had a distinct winter pattern. During 1997 only 46% of the hospitals reporting diarrhea in children used the specific code for rotavirus, and 12% of hospitals reported rotavirus in >30% of all diarrhea-associated hospitalizations. Infants <4 months of age were more likely than older children to be nosocomially infected with rotavirus and had a higher proportion of congenital malformations. CONCLUSION: In New York State diarrhea is a common hospital discharge diagnosis and contributes approximately 13% of all hospitalizations among children <5 years of age. When hospitals with maximum recording were used as a reference point, >30% of diarrhea hospitalizations were recorded as likely the result of rotavirus.

Trends from an HIV seroprevalence study among childbearing women in New York State from 1988 through 2000: a valuable epidemiologic tool.

BACKGROUND: Women in New York State are heavily affected by the human immunodeficiency virus (HIV) epidemic. New York has had the largest number of births to HIV-infected pregnant women in the United States. Data collected as part of the Survey of Childbearing Women have been valuable for assessing the impact of the disease on the women of New York. OBJECTIVE: To assess HIV prevalence trends among childbearing women in New York State. DESIGN, SETTING, AND PARTICIPANTS: An unlinked HIV seroprevalence study was conducted among all women residing in and giving birth in New York State from 1988 through 2000. Trend and cohort analyses were conducted. Main Outcome Measure HIV prevalence, defined as the number of HIV-positive specimens divided by the total number of HIV-positive and HIV-negative specimens, by geographic region, racial/ethnic group, and maternal age cohort. RESULTS: Trends indicated a steady decline in HIV prevalence in New York State. New York City had a 49% decrease in prevalence between 1988 through 1989 and 1999 through 2000, and the rest of the state showed a 24% decline. However, birth cohort analysis indicated different patterns in trend by subpopulation, with some groups experiencing little or no decline. CONCLUSION: This study reports on the only statewide population-based HIV prevalence data currently available for childbearing women; these data have been a valuable tool for monitoring trends, targeting resources, and evaluating programs and policies.

Effect of sodium bicarbonate supplementation on 2000-m rowing performance.

UNLABELLED: The ability to buffer H+ could be vital to exercise performance, as high concentrations of H+ contribute to the development of fatigue. PURPOSE: The authors examined the effect of sodium bicarbonate (SB) supplementation on 2000-m rowing-ergometer performance. METHODS: Twenty male rowers (age 23 ± 4 y, height 1.85 ± 0.08 m, mass 82.5 ± 8.9 kg, 2000-m personal-best time 409 ± 16 s) completed two 2000-m rowing-ergometer time trials, separated by 48 h. Participants were supplemented before exercise with 0.3 g/kg body mass of SB or a placebo (maltodextrin; PLA). The trials were conducted using a double-blinded, randomized, counterbalanced crossover study design. Time to complete the 2000-m and time taken for each 500-m split were recorded. Blood lactate, bicarbonate, pH, and base excess were determined preexercise, immediately postexercise, and 5 min postexercise. Performance data were analyzed using paired t tests, as well as magnitude-based inferences; hematological data were analyzed using a repeated-measures ANOVA. RESULTS: Using paired t tests, there was no benefit of SB over PLA (P = .095). However, using magnitude-based inferences there was a likely beneficial effect of SB compared with PLA (PLA 412.0 ± 15.1 s, SB 410.7 ± 14.9 s). Furthermore, SB was 0.5 ± 1.2 s faster than PLA in the third 500 m (P = .035; possibly beneficial) and 1.1 ± 1.7 s faster in the fourth 500 m (P = .004; very likely beneficial). All hematological data were different between SB and PLA and were different from preexercise to postexercise. CONCLUSION: SB supplementation is likely to be beneficial to the performance of those competing in 2000-m rowing events, particularly in the second half of the event.

Dental caries and oral health practices among 12 year old children in Nairobi West and Mathira West Districts, Kenya.

BACKGROUND: Dental caries is a common disease in children which causes pain with resultant effect on various physiological and social functions. The main objective of the study was to determine the association between dental caries and oral health knowledge and practice among children in Nairobi West and Mathira West Districts. METHODS: A cross-sectional study was conducted among 639 children aged 12 years attending public primary schools in Nairobi West and Mathira West districts between August 2009-February 2010. A questionnaire was used to determine the level of knowledge and practices employed. Oral screening was performed using World Health Organisation (WHO) recommended methods. Dental caries was measured using the Decayed, Missing, Filled Teeth (DMFT) index. RESULTS: Nairobi West District had significantly higher caries prevalence of 37.5% than Mathira West District (24.0%). The DMFT in Nairobi West District was 0.76 ± 1.2, while in Mathira West District it was 0.36 ± 0.7. On multivariate analysis high consumption of soda was found to be a significant risk factor for dental caries in Nairobi West District(Odds Ratio (OR) = 3.0). In Mathira West District having an illiterate mother was a significant risk factor for dental caries (OR = 4.3). CONCLUSION: Countrywide intensive oral health promotion should be carried out especially in urban areas, to reduce the higher prevalence of dental caries. The school health policy should be used to promote oral health by provision of oral health instructions and highlighting harmful dietary practices. Preventive practices such as regular dental checkups should be advocated and promoted in schools.