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Peritoneal spread is the primary mechanism of metastasis of ovarian cancer, and survival of ovarian cancer cells in the peritoneal cavity as nonadherent spheroids and their adherence to the mesothelium of distant organs lead to cancer progression, metastasis, and mortality. However, the mechanisms that govern this metastatic process in ovarian cancer cells remain poorly understood. In this study, we cultured ovarian cancer cell lines in adherent and nonadherent conditions in vitro and analyzed changes in mRNA and protein levels to identify mechanisms of tumor cell survival and proliferation in adherent and nonadherent cells. EGFR or ERBB2 upregulated ZEB1 in nonadherent cells, which caused resistance to cell death and increased tumor-initiating capacity. Conversely, Forkhead box M1 (FOXM1) was required for the induction of integrin β1, integrin-α V, and integrin-α 5 for adhesion of cancer cells. FOXM1 also upregulated ZEB1, which could act as a feedback inhibitor of FOXM1, and caused the transition of adherent cells to nonadherent cells. Strikingly, the combinatorial treatment with lapatinib [dual kinase inhibitor of EGFR (ERBB1) and ERBB2] and thiostrepton (FOXM1 inhibitor) reduced growth and peritoneal spread of ovarian cancer cells more effectively than either single-agent treatment in vivo. In conclusion, these results demonstrate that FOXM1 and EGFR/ERBB2 pathways are key points of vulnerability for therapy to disrupt peritoneal spread and adhesion of ovarian cancer cells.Significance:This study describes the mechanism exhibited by ovarian cancer cells required for adherent cell transition to nonadherent form during peritoneal spread and metastasis.

Supplementary Spread Sheet 1

Aim:To assess the knowledge, attitude and practices related to hand hygiene among first year undergraduates of Nursing and Pharmacy in Durg district. Design:Comparative cross sectional study. Methods:Study was conducted among two groups of undergraduate students belonging to the first year of their respective course. The first group included 118 students pursuing first year of Bachelors in Pharmacy course at a private institute of pharmaceutical science and research and the other group included 181 students pursuing first year of Bachelors of Science, Nursing course at a private nursing institute located in Durg District. All study subjects were surveyed with a questionnaire regarding their Knowledge, attitude and practices related to hand hygiene. Statistical Analysis:Shapiro Wilk test, Z- test, Mann Whitney U test. Results:A questionnaire based responses was obtained from 299 first year undergraduate students of nursing and pharmacy. Nursing students had better knowledge (P Conclusion:Our study emphasizes the need for educational and training programs about hand hygiene and its techniques, risks related to improper hand hygiene. There is also a need to augment the availability and accessibility of hand hygiene resources. Adequate knowledge and training regarding hand hygiene may help bring about a change in attitude towards hand hygiene, better compliance, reducing the transmission of infections and, ultimately, building a healthy society. &nbsp

Worldwide COVID-19 pandemic had led to a prolonged stressful condition and bring about more psychological and social effects in the community. This condition is commonly seen in each group and more commonly it has affected in children, older peoples and even the health workers who are exposed and likely to bring about the condition of stress, anxiety, uneasiness and depression. These prolonged psychosocial issues may result in mental health problems and long-term consequence on the mental functioning and coping capacities of family members. The aim of this article is to explain some of the psychosocial impacts, and more is emphasis given in identifying these psychosocial problems and some of the strategies which can be used to overcome these issues.

Background: In January 2020, the World Health Organization (WHO) declared that Covid-19 is characterized as pandemic. It is a major health crisis affecting several nations. The crisis generates stresses throughout the population. This pandemic condition is leading the public to experience psychosocial problems such as post- traumatic stress disorders, psychological distress, depression and anxiety. Objectives: 1. To assess the psychosocial issues of family members of third year BSc nursing students regarding the covid-19 pandemic. 2. To find out the association between the psychosocial issues with demographic variables. 3. To implement psychosocial education to overcome the psychosocial issues related to covid -19 pandemic. Methodology: A Non-experimental descriptive survey design was used to assess the perceived psychosocial issues associated with COVID-19 pandemic among the family members. The study was conducted among 50 samples selected by inclusion and exclusion criteria through random sampling technique. The data was collected by using a baseline data questionnaire. The data were collected, tabulated and analyzed by using descriptive and inferential statistics. Chi-square test was used to find out the association between selected demographic variables and psychological issues. Results: In the present study, the finding shows that the 76% of the parents have moderate impact on daily life style. 64% of parents have a mild impact on finance. 61% of the parents have mild insomnia. 60% of the parents have moderate level of anxiety and depression. Conclusion: The study concludes that psychosocial issues are a common phenomenon among the parents and grandparents.

The aim of this study was to explore association between hypermobility and osteoarthritis (OA) at the first carpometacarpal (CMC) joint, using magnetic resonance imaging (MRI) to identify early change in women at high risk of developing OA but without yet established diagnoses.For this observational study, 33 women (aged 30-50 years) with self-reported history of maternal hand OA but without personal diagnoses of OA were recruited. Participants completed a 5-point hypermobility questionnaire. The 20 participants with 2 or more positive responses were categorized with "high hypermobility scores." The remaining 13 were categorized with "low hypermobility scores." Data collection included functional index, hand pain measure, parity, smoking status, and body mass index. Each participant underwent dominant hand radiographic and MRI examination. Imaging studies were interpreted by assessors blinded to hypermobility score categorization.No significant differences in age, body mass index, parity, functional index, or pain scores were observed between higher and lower hypermobility score groups. Similarly, there were no significant differences between groups for radiographic changes. However, significantly higher proportions of women with higher hypermobility scores were observed on MRI to have abnormalities of trapezium cartilage (75% vs. 38%), metacarpal cartilage (80% vs. 38%), and trapezium bone (70% vs. 31%); p0.05 for all.First CMC joint structural abnormalities were more frequently observed in women with higher hypermobility scores. Identification of early preradiographic changes in this group supports the concept that early-life joint laxity may contribute to future OA predisposition. Magnetic resonance imaging may be a preferred imaging test for detection of early cartilage changes in people at high risk of CMC joint OA.

To estimate provincial all-cause mortality rates of Saskatchewan people with rheumatoid arthritis (RA) for comparison with the general population over time and between different geographic regions.Saskatchewan provincial administrative health databases (2001-2019) were utilized as data sources. Two RA case definitions were employed: (1) ≥ 3 physician billing diagnoses, at least 1 from a specialist (rheumatologist, general internist or orthopaedic surgeon) within 2 years; (2) ≥ 1 hospitalization diagnosis (ICD-9 code 714, and ICD-10-CA codes M05, M06). Data from these definitions were combined to create an administrative data RA cohort. All-cause mortality rates across geographic regions, between rural/urban residences and between sexes were examined.Over an 18-year span, between fiscal-year 2001-2002 and fiscal-year 2018-2019, age- and sex-adjusted mortality rates ranged from 17.10 to 21.04 (95% CI 14.77, 19.44; 18.03, 24.05)/1000 RA person-years, compared with mortality rates for the general Saskatchewan population without RA, which ranged from 9.37 to 10.88 (95% CI 9.23, 9.51; 10.72, 11.05)/1000 person-years. Fiscal-year mortality rate ratios ranged from 1.82 to 2.13 (95% CI 1.56, 2.13; 1.83, 2.46). Provincial mortality rates were higher in men than in women for both general and RA populations. Northern Saskatchewan mortality rates were significantly higher in the general population but did not achieve significance compared with other provincial regions for the RA population. Regression analysis identified age, male sex, RA and geographic region as factors contributing to increased mortality. A trend towards lower mortality rates over time was observed.Higher mortality rates were observed in the RA population overall. Men had higher mortality rates, as did residents of Northern Saskatchewan compared with residents of other regions for the general population.RéSUMé: OBJECTIFS: Estimer les taux de mortalité provinciaux, toutes causes confondues, des habitants de la Saskatchewan atteints de polyarthrite rhumatoïde (PR) pour les comparer aux taux dans la population générale au fil du temps et entre différentes régions géographiques. MéTHODE: Nos données sont extraites des bases de données administratives sur la santé de la Saskatchewan (2001–2019). Deux définitions de cas ont été employées pour la PR : 1) ≥ 3 factures de diagnostic médical, dont au moins une d’un(e) spécialiste (rhumatologue, interniste général[e] ou chirurgien[ne] orthopédiste) en l’espace de deux ans; 2) ≥ 1 diagnostic d’hospitalisation (code CIM-9 714 et codes CIM-10-CA M05 et M06). Les données de ces définitions ont été combinées pour créer une cohorte de personnes atteintes de PR dans les données administratives. Les taux de mortalité toutes causes confondues entre les régions géographiques, entre les lieux de résidence urbains et ruraux et entre les sexes ont été examinés. RéSULTATS: En l’espace de 18 ans, entre les exercices 2001-2002 et 2018-2019, les taux de mortalité rajustés selon l’âge et le sexe ont varié entre 17,10 et 21,04 (IC de 95 % : 14,77-19,44; 18,03-24,05)/1000 personnes-années pour les personnes atteintes de PR, tandis que les taux de mortalité de la population générale de la Saskatchewan non atteinte de PR se sont situés entre 9,37 et 10,88 (IC de 95 % : 9,23-9,51; 10,72-11,05)/1000 personnes-années. Les rapports de taux de mortalité par exercice ont varié entre 1,82 et 2,13 (IC de 95 % : 1,56-2,13; 1,83-2,46). Les taux de mortalité provinciaux des hommes étaient supérieurs à ceux des femmes, tant dans la population générale que chez les personnes atteintes de PR. Les taux de mortalité dans le Nord de la Saskatchewan étaient sensiblement plus élevés que dans les autres régions de la province pour la population générale, mais pas sensiblement plus élevés pour la population atteinte de PR. Selon les analyses de régression, l’âge, le sexe masculin, la PR et la région géographique étaient des facteurs contribuant à une mortalité accrue. Une tendance à la baisse des taux de mortalité au fil du temps a été observée. CONCLUSION: Dans la population atteinte de PR, des taux de mortalité plus élevés ont été observés globalement. Dans la population générale, les taux de mortalité des hommes et ceux des résidents du Nord de la Saskatchewan étaient plus élevés que ceux des résidents des autres régions.

An increased expression of oncogenic microRNA miR551b-3p (also known as miR551b) occurs in a subset of breast cancer due to genomic amplification of 3q26.2 locus. Using in silico and clinical sample analysis of breast cancer patient datasets, we identified that those breast cancer samples that encompass miR551b amplification express high levels of STAT3 mRNA and Oncostatin (OSM) family genes in triple-negative breast cancer (TNBC). Furthermore, high expression of Oncostatin family genes associates with poor outcome in estrogen receptor- negative breast cancer patients. In this study, we identified a previously unexplored mechanism that miR551b-3p promotes breast cancer progression and tumor growth by direct interaction of miR551b-3p with STAT3 promoter thereby activating STAT3 transcription. As a consequence, STAT3 upregulates a cytokine Oncostatin and its receptor Oncostatin M receptor (OSMR) and their interaction further induces STAT3 phosphorylation and an autocrine self-reinforcing loop in TNBC cells. In this study, we demonstrate that overexpression of miR551b-3p promoted proliferation, invasion and migration, epithelial to mesenchymal transition (EMT) and spheroid formation of breast cancer cells and its inhibition decreased the expression of miR551b-3p by inhibiting OSM, OSMR, IL6ST, IL31RA, phosphorylated and total STAT3 in breast cancer cells and reduced tumor cell growth. Overall, our results provide the first evidence that miR551b regulates OSM family gene expression by activating STAT3 and thereby promoting tumor cell growth and metastasis in breast cancer cells. Therefore, targeting miR-551b-3p-STAT3-OSMR axis and inhibiting their levels will provide an unprecedented therapeutic opportunity in breast cancer. Citation Format: Anjali Geethadevi, Deepak Parashar, Miriam Ragle Aure, Jasmine George, Changliang Chen, Jyotsna Mishra, Andliena Tahiri, Bindu Nair, Amadou Camara, Vessela N Kristensen, Sunila Pradeep, Pradeep Chaluvally Raghavan. miR551b-3p promotes Oncostatin M signaling in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-04.

Summary: Genomic amplification of 3q26.2 locus leads to the increased expression of microRNA 551b-3p (miR551b-3p) in triple-negative breast cancer (TNBC). Our results demonstrate that miR551b-3p translocates to the nucleus with the aid of importin-8 (IPO8) and activates STAT3 transcription. As a consequence, miR551b upregulates the expression of oncostatin M receptor (OSMR) and interleukin-31 receptor-α (IL-31RA) as well as their ligands OSM and IL-31 through STAT3 transcription. We defined this set of genes induced by miR551b-3p as the “oncostatin signaling module,” which provides oncogenic addictions in cancer cells. Notably, OSM is highly expressed in TNBC, and the elevated expression of OSM associates with poor outcome in estrogen-receptor-negative breast cancer patients. Conversely, targeting miR551b with anti-miR551b-3p reduced the expression of the OSM signaling module and reduced tumor growth, as well as migration and invasion of breast cancer cells. : Parashar et al. demonstrate that the mature microRNA-551b-3p translocates to the nucleus for transcriptional activation of STAT3 gene. As a consequence, miR551b activates an autocrine signaling loop through the upregulation of oncostatin family genes, including oncostatin, and its receptors for the growth and metastasis of triple-negative breast cancer. Keywords: miR551b, oncostatin, STAT3, OSMR, miRNA-therapy, IPO8, RNAi

Background. Detection of ankylosing spondylitis (AS) in the preclinical stage could help prevent long term morbidity in this patients’ population. The aim of this study was to examine the prevalence of active sacroiliitis in first-degree relatives of AS patients using MRI with clinical and laboratory correlations as these patients may benefit from MRI screening and early treatment.Methods. Seventeen first-degree relatives of AS patients were recruited prospectively. AS screening questionnaires (Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index & Visual Analogue Scale), blood tests (C-Reactive Protein, HLA-B27), and an MRI of the SIJs were taken. Two musculoskeletal radiologists interpreted the MRI scans, and two physiotherapists applied four symptom provocation tests (Gaenslen's test, posterior pelvic pain provocation test, Patrick's Faber (PF) test and palpation of the long dorsal SIJ ligament test), and two functional movement tests (active straight leg raise and Stork test). Results. Seven (41%) of the 17 participants demonstrated MRI evidence of active sacroiliitis. Of the 7 participants with active sacroiliitis, two (29%) had no history of recent low back pain (LBP), two (29%) had negative HLA-B27, and one (14%) participant had neither back pain nor positive HLA-B27. The Cohen's Kappa score for the interobserver agreement between the radiologists was 1.00 (p-value ). Despite fair to strong between therapist agreement for the physical test outcomes (Kappa 0.26 to 1.00), the physical test results per se did not have any predictive association with a positive MRI.Conclusions. MRI detected active sacroiliitis in 41% of first-degree relatives of AS patients. The lack of a history of prior LBP or positive HLA-B27 in active sacroiliitis participants might suggest that MRI screening for this high-risk population is warranted; however, further larger studies are needed to help elucidate its cost-effectiveness and long-term benefits.

Background: Chronic Obstructive Pulmonary Disease(COPD), pneumothorax and asthma are climate sensitive diseases contributing a significant proportion of the respiratory disease morbidity. Even when the monsoon rainfall is high, recent years have witnessed an increase in the average temperature in Kerala. The study aims to determine the trends in hospital admissions for these diseases and associated factors during 2011 to 2015 at a tertiary care hospital in Thiruvananthapuram, India. Methods: Record based retrospective study was done at Chest Disease Hospital at Thiruvananthapuram, Kerala. Data regarding the patients admitted from January 2011 to December 2015 was collected and trend analysis was done. Change in occurrence over the 5 year period was estimated and associations with co-existing diseases were determined. Results:A significant difference in the occurrence of COPD cases was seen during the months of July to December when compared between 2011 and 2015 with a significant rise in mean age of occurrence(p

We aimed to analyze which medical school experiences contribute to success in an increasingly competitive CaRMS match.We surveyed all matched University of Saskatchewan 2019 medical graduates on characteristics of their applications: number of program applications, interviews obtained, experiences (research, volunteer, leadership), awards and money spent on the residency match process, and qualitative reflections on the process. Using published CaRMS statistics based on number of positions versus applicants, specialties were divided into high availability/low demand (HA) (e.g. family and internal medicine) and low availability/high demand (LA) (e.g. dermatology and emergency medicine). Quantitative results were analyzed using descriptive statistics, chi-square and t-tests, and qualitative results thematically.Data from 27 of 94 matched students were included. LA applicants were more likely to report at least one research project on their CV (66.67% among LA vs. 15.38% among HA,LA applicants cited more research projects and presentations, spent more elective weeks outside Saskatchewan, but were otherwise similar to HA applicants. Further studies should be done on student factors in the residency match process.Nous visions à analyser quelles expériences durant le course de médecine contribuent à la réussite d’un jumelage de plus en plus compétitif par le CaRMS.Nous avons enquêté à propos des caractéristiques des candidatures de tous les diplômés en médecine jumelés en 2019 à l’Université de la Saskatchewan: nombre de demandes effectuées, les entrevues obtenues, les expériences (recherche, bénévolat, leadership), les prix et les sommes dépensées sur le CaRMS, et leurs réflexions qualitatives sur le processus du CaRMS. À l’aide des statistiques publiées par le CaRMS fondées sur le nombre de postes par rapport au nombre de candidats, les spécialités ont été réparties en haute disponibilité/faible demande (HA) (p. ex., médecine familiale et interne) et faible disponibilité/demande élevée (LA) (p. ex., dermatologie et médecine d’urgence). Les résultats quantitatifs ont été analysés à l’aide de statistiques descriptives, chi carré et tests t, et les résultats qualitatifs ont fait l’objet d’une analyse thématique.Les données de 27 des 94 étudiants appariés ont été incluses. Les candidats LA étaient plus susceptibles de déclarer au moins un projet de recherche sur leur CV (66,67 % parmi les LA c. 15,38 % chez les HA,Les candidats LA ont cité davantage de projets et de présentations de recherche, davantage de semaines de stages à option à l’extérieur de la Saskatchewan et plus de dépenses encourues en lien avec les stages à option, mais étaient autrement semblables aux candidats HA. D’autres études devront être réalisées sur les facteurs étudiants dans le jumelage du CaRMS.

Objective The aim of the present study was to evaluate whether rheumatoid arthritis (RA) patients followed longitudinally using video-conferencing and inter-professional care support have comparable disease control to those followed in traditional in-person rheumatology clinics. Methods This was a randomized controlled trial for 85 RA patients allocated to either traditional in-person rheumatology follow-up or video-conferenced follow-up with urban-based rheumatologists and rural in-person physical therapist examiners. Follow-up was every 3 months for 9 months. Outcome measures included disease activity metrics (disease activity in 28 joints with CRP measure score [DAS28-CRP], and RA disease activity index [RADAI]), modified health assessment questionnaire (mHAQ), quality of life (EuroQOL five dimensions questionnaire [EQ5D]) and patient satisfaction (nine-item visit-specific satisfaction questionnaire [VSQ9]). Results Of 85 participants, 54 were randomized to the video-conferencing team model and 31 to the traditional clinic (control group). Dropout rates were high, with only 31 (57%) from the video-conferencing and 23 (74%) from the control group completing the study. The mean age for study participants was 56 years; 20% were male. Mean RA disease duration was 13.9 years. There were no significant between-group differences in DAS28-CRP, RADAI, mHAQ or EQ5D scores at baseline or over the study period. Satisfaction rates were high in both groups. Conclusions We found no evidence of a difference in effectiveness between inter-professional video-conferencing and traditional rheumatology clinic for both the provision of effective follow-up care and patient satisfaction for established RA patients. High dropout rates reinforce the need for consultation with patients' needs and preferences in developing models of care. While use of video-conferencing/telehealth technologies may be a distinct advantage for some patients, there may be loss of travel-related auxiliary benefits for others.

Purpose To compare the effects of nine months of exercise training and ibuprofen supplementation (given immeditately after exercise sessions) on bone and muscle in postmenopausal women. Methods In a double-blind randomized trial, participants (females: n = 90, mean age 64.8, SD 4.3 years) were assigned (computer generated, double blind) to receive supervised resistance training or stretching 3 days/week, and ibuprofen (400 mg, post-exercise) or placebo (i.e. 4 groups) for 9 months. In this proof-of-concept study the sample size was halved from required 200 identified via 90% power calculation. Baseline and post-intervention testing included: Dual energy x-ray absorptiometry (DXA) for lumbar spine, femoral neck, and total body areal bone mineral density (aBMD); geometry of proximal femur; total body lean tissue and fat mass; predicted 1-repetition maximum muscle strength testing (1RM; biceps curl, hack squat). Results Exercise training or ibuprofen supplementation had no effects on aBMD of the lumbar spine, femoral neck, and total body. There was a significant exercise × supplement × time interaction for aBMD of Ward's region of the femoral neck (p = 0.015) with post hoc comparison showing a 6% decrease for stretching with placebo vs. a 3% increase for stretching with ibuprofen (p = 0.017). Resistance training increased biceps curl and hack squat strength vs. stretching (22% vs. 4% and 114% vs. 12%, respectively) (p, Highlights • Ibuprofen independently (i.e. without exercise) may have some benefits on bone. • Ibuprofen was not effective if given immediately after resistance training. • Ibuprofen may be a novel therapy to prevent bone loss associated with inflammation.

Peritoneal spread is the primary mechanism of metastasis of ovarian cancer, and survival of ovarian cancer cells in the peritoneal cavity as nonadherent spheroids and their adherence to the mesothelium of distant organs lead to cancer progression, metastasis, and mortality. However, the mechanisms that govern this metastatic process in ovarian cancer cells remain poorly understood. In this study, we cultured ovarian cancer cell lines in adherent and nonadherent conditions in vitro and analyzed changes in mRNA and protein levels to identify mechanisms of tumor cell survival and proliferation in adherent and nonadherent cells. EGFR or ERBB2 upregulated ZEB1 in nonadherent cells, which caused resistance to cell death and increased tumor-initiating capacity. Conversely, Forkhead box M1 (FOXM1) was required for the induction of integrin β1, integrin-α V, and integrin-α 5 for adhesion of cancer cells. FOXM1 also upregulated ZEB1, which could act as a feedback inhibitor of FOXM1, and caused the transition of adherent cells to nonadherent cells. Strikingly, the combinatorial treatment with lapatinib [dual kinase inhibitor of EGFR (ERBB1) and ERBB2] and thiostrepton (FOXM1 inhibitor) reduced growth and peritoneal spread of ovarian cancer cells more effectively than either single-agent treatment in vivo. In conclusion, these results demonstrate that FOXM1 and EGFR/ERBB2 pathways are key points of vulnerability for therapy to disrupt peritoneal spread and adhesion of ovarian cancer cells. Significance: This study describes the mechanism exhibited by ovarian cancer cells required for adherent cell transition to nonadherent form during peritoneal spread and metastasis.

Background Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthritis. Understanding the incidence and prevalence of RA within the province facilitates appropriate health care resource planning. Objective To estimate the incidence/prevalence of RA over time for the overall provincial population, for specific age range categories, and for gender. Methods Saskatchewan Provincial Administrative Health Databases (2001–2014) were utilized as data sources. Two RA case-definitions were employed: 1) > three physician billing diagnoses, at least one of which was submitted by a specialist (rheumatologist, general internist or orthopedic surgeon) within 2 years; 2) > one hospitalization diagnosis (ICD-9-CM code-714, and ICD-10-CA code-M05). Data from these definitions were combined to identify incident and prevalent RA cases. Using this data, annual incidence and prevalence rates were calculated for the provincial population, specified age range categories and gender categories. Results The number of RA cases meeting the case definition increased from 3731 to 6223 over the study period. The incidence of RA disease demonstrated variation within the study period with age and sex adjusted incidence ranging from 33.6 (95% CI 29.9–37.6) per 100,000 to 73.1 (95% CI 67.6–79.0) per 100,000. The prevalence of RA increased over time from 482 (95% CI 466.7–497.7) per 100,000 in 2001–2002 to 683.4 (95% CI 666.6–700.6) per 100,000 in 2014–2015. Both incidence and prevalence rates rose with increasing age. Women were found to have higher incidence and prevalence rates compared to men. Conclusion In Saskatchewan, the overall prevalence of RA is rising while there has been variability in the incidence.

Brain-derived neurotrophic factor (BDNF) is an active neurotrophin abundantly expressed throughout the nervous system. It plays an important role in synaptic transmission, plasticity, neuronal proliferation, differentiation, survival, and death. The Bdnf gene in rodents has eight non-coding exons and only a single coding exon (IX). Despite its recognized regulation by neuronal activity, relatively little is known about its transcriptional regulation, and even less about the transcription factor candidates that may play such a role. The goal of the present study was to probe for such a candidate that may regulate exon IX in the rat Bdnf gene. Our in silico analysis revealed tandem binding sites for nuclear respiratory factor 2 (NRF-2) on the promoter of exon IX. NRF-2 is of special significance because it co-regulates the expressions of mediators of energy metabolism (cytochrome c oxidase) and mediators of neuronal activity (glutamatergic receptors). To test our hypothesis that NRF-2 also regulates the Bdnf gene, we performed electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), promoter cloning, and site-directed mutagenesis, real-time quantitative PCR (RT-qPCR), and Western blotting analysis. Results indicate that NRF-2 functionally regulates exon IX of the rat Bdnf gene. The binding sites of NRF-2 are conserved between rats and mice. Overexpressing NRF-2 up-regulated the expression of Bdnf exon IX, whereas knocking down NRF-2 down-regulated such expression. These findings are consistent with our hypothesis that NRF-2, in addition to regulating the coupling between neuronal activity and energy metabolism, also regulates the expression of BDNF, which is intimately associated with energy-demanding neuronal activity.

Objectives The aim of the present study was to identify potential barriers for access to medical and allied health services from the perspective of rural and Northern Saskatchewan rheumatoid arthritis (RA) patients. Methods A total of 100 adults with established RA, residing in rural and Northern Saskatchewan, were recruited from two rheumatology practices. Structured interviews with standardized scripts solicited patient perspectives on appointment waiting times, travel required to access medical services and satisfaction with healthcare provision. Thematic analysis was employed for qualitative data. Results Patients-reported concerns regarding waiting time for their first rheumatology appointment. There was reduced access to allied health professionals, with only 53% of the participants having seen a physiotherapist (PT), and only 26% an occupational therapist (OT). Patients had similar driving distances to their family physician, PT, pharmacy and laboratory services but commuted significantly further for rheumatologist and OT services. There were high levels of satisfaction with their rheumatologist and family physician appointments (8.96 and 8.04 on a ten-point scale). Patients with longer travel times had higher satisfaction with their health care appointments: Patients who travelled one, two and more than two hours had satisfaction scores of 0.93, 0.88 and 1.32 points higher on a ten-point scale (p

The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors mediating fast excitatory synaptic transmission in the brain. The regulation of the four subunits of AMPA receptors, GluA1-4, is poorly understood. Excitatory synaptic transmission is highly energy-demanding, and this energy is derived mainly from the oxidative pathway. Recently, we found that specificity factor regulates all subunits of cytochrome c oxidase (COX), a critical energy-generating enzyme. COX is also regulated by nuclear respiratory factor 1 (NRF-1), which transcriptionally controls the Gria2 (GluA2) gene of AMPA receptors. The goal of the present study was to test our hypothesis that Sp-factors (Sp1, Sp3, and/or Sp4) also regulate AMPA subunit genes. If so, we wish to determine if Sp-factors and NRF-1 function via a complementary, concurrent and parallel, or a combination of complementary and concurrent/parallel mechanism. By means of multiple approaches, including electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutations, real-time quantitative PCR, and western blot analysis, we found that Sp4, but not Sp1 or Sp3, regulates the Gria2, but not Gria1, 3, or 4, subunit gene of the AMPA receptor in a concurrent and parallel manner with NRF-1. Thus, Sp4 and NRF-1 both mediate the tight coupling between neuronal activity and energy metabolism at the transcriptional level.

The increasing use of new technologies and virtual communication is promoting an individual to use personal computers, mobile phones and tablets which is causing changes in persons daily habits and behavior. In other words, we can suspect the individual as a social phobia, were the dependency on communication is through virtual environment, and use of mass media can overcome this stress by avoiding the individual on direct bases. The aim of this article is to make aware to the society regarding Nomophobia, how the mobile phones are insisting the person to be more dependable on it rather than giving importance to social interaction. Moreover, the emphasis is on the bad effects which can be seen if an individual is diagnosed as nomophobia and can be treated in early stage itself. The session also include how smart phones addiction can be overcome and with the help of self-assessment questionnaire it would be easier to identify our self whether an individual is having nomophobia. Nomophobia can be treated with the help of certain therapies and drugs even.

Introduction/Purpose: Resistance training with ibuprofen supplementation may improve musculoskeletal health in postmenopausal women. The study purpose was to determine the efficacy of resistance training and ibuprofen supplementation on bone and muscle properties in postmenopausal women. Methods: Participants (n = 90, 65.3 ± 4.9 yr) were randomly assigned to: supervised resistance training or stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo supplementation for 3 d·wk−1 (9 months). Baseline and postintervention measurements included distal and shaft scans of the forearm and lower leg using peripheral quantitative computed tomography. Distal site outcomes included cross-sectional area, content, and density for total and trabecular bone, as well as estimated bone strength in compression. Shaft site outcomes included total bone area; cortical bone area, content, and density; estimated bone strength in torsion; and muscle area and density. Results: Exercise–supplement–time interactions for total bone content at the distal radius (P = 0.009) and cortical density at the radius shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased total bone content (−1.5%) at the distal radius in comparison to the resistance training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in cortical density at the radius shaft differed between the stretching with placebo and ibuprofen supplementation groups (−1.8% vs 1.1%; P = 0.050). Resistance training preserved muscle density in the lower leg more so than stretching (−3.1% vs −5.4%; P = 0.015). Conclusions: Ibuprofen consumed immediately after resistance training had a deleterious effect on bone mineral content at the distal radius, whereas resistance training or ibuprofen supplementation individually prevented bone loss. Resistance training prevented muscle density decline in the lower leg.

1 B-404,Neelsidhi Atlantis, PIIT, Navi Mumbai, India 2 Sector 19A,Nerul, New Panvel, Navi Mumbai, India Email: bindu_k_nair@hotmail.com, ujwal.harode@gmail.com ABSTRACT An important and very crucial component of many systems involving images is the edge detection which includes object detectors and image segmentation algorithms. Edge patches always shows shapes of its inherent structure, like T junctions or lines. Taking advantage of the shapes available in the images we get to know of an edge detector which is accurate and efficient. In this approach the structured labels is robustly mapped to a space that is discrete by which evaluation of the measure of the standard information gain is possible. The outcome is a way that shows a real time performance which is many times faster than any of the traditional and modern approaches available today, which also achieves the best results for edge detection both the Berkeley Segmentation Dataset and Benchmark (BSDS 500) and the NYU depth dataset. This approach also shows its strength as a an edge detector that can be used for any regular purpose by displaying how this method generalize across all datasets

Sleep problems are common concerns in rheumatology patients and have been independently linked to increased pain perception and fatigue severity. Evidence supports an increased prevalence of primary sleep disorders, including sleep apnoea, in some rheumatic disease populations, particularly RA. Obstructive sleep apnoea is a significant public health concern and contributes to increased cardiovascular morbidity and mortality. Patients with obstructive sleep apnoea have also been found to have elevations in circulating acute-phase markers and pro-inflammatory cytokines. Co-existence of sleep apnoea in rheumatic disease patients may influence the severity of reported symptoms of pain and fatigue, accelerate the risk of cardiovascular events and possibly influence levels of circulating inflammatory markers and mediators. In this article we review the risk factors, prevalence and impact of sleep apnoea from a rheumatological perspective. Additionally, we recommend considering sleep apnoea screening in patients with rheumatic disease and, when appropriate, referral to a specialized sleep disorders clinic.

Objective Subjective reports of sleep dysfunction are common in people with rheumatoid arthritis (RA). Our objective was to determine whether excess sleepiness in RA is associated with polysomnographic (PSG) abnormalities. Methods Twelve RA participants with abnormal sleep scores were identified in clinic and age/gender matched to RA participants with normal Epworth Sleepiness Scale (ESS) scores. A total of 25 participants were recruited. All participants underwent overnight PSG studies with measurement of apnoea–hypopnoea indexes (AHI). Questionnaire instruments, including the ESS, Berlin questionnaire for sleep apnoea risk, visual analogue scale for fatigue, modified Health Assessment Questionnaire (mHAQ) and the Center for Epidemiologic Studies – Depression (CES-D) score, along with RA assessments, were reapplied on the PSG study night. Results Seven men and 18 women participated. Ten participants had abnormal ESS scores and 15 had normal ESS scores on the PSG night. PSG data revealed that 68% of patients had abnormal AHI (≥ 5). Abnormal ESS (> 10) had an 80% positive predictive value (PPV) for abnormal AHI; the negative predictive value (NPV) of normal ESS was 40%. By contrast, high-risk categorization for obstructive sleep apnoea (OSA) by the Berlin questionnaire had a PPV of 77.8%, and for low-risk status, an NPV of 37.5%. Conclusions In the present study population, there was a high prevalence of abnormal AHI consistent with OSA. An abnormal ESS had high positive predictive value for an abnormal AHI. Copyright © 2012 John Wiley & Sons, Ltd.

Background: Poor sleep health is increasingly recognized as contributing to decreased quality of life, increased morbidity/mortality and heightened pain perception. Our purpose in this study was to observe the effect on sleep parameters, specifically sleep efficiency, in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor alpha (anti-TNF-α) therapy. Methods: This was a prospective observational study of RA patients with hypersomnolence/poor sleep quality as defined by the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Study patients underwent overnight polysomnograms and completed questionnaire instruments assessing sleep prior to starting anti-TNF-α therapy and again after being established on therapy. The questionnaire included the ESS, PSQI, the Berlin instrument for assessment of obstructive sleep apnea (OSA) risk, restless legs syndrome (RLS) diagnostic criteria, and measures of disease activity/impact. Results: A total of 12 RA patients met inclusion criteria, of which 10 initiated anti-TNF-α therapy and underwent repeat polysomnograms and questionnaire studies approximately 2 months later. Polysomnographic criteria for OSA were met by 60% of patients. Following anti-TNF-α therapy initiation, significant improvements were observed by polysomnography (PSG) for sleep efficiency, increasing from 73.9% (SD 13.5) to 85.4% (SD 9.6) ( p = 0.031), and ‘awakening after sleep onset’ time, decreasing from 84.1 minutes (SD 43.2) to 50.7 minutes (SD 36.5) ( p = 0.048). Questionnaire instrument improvements were apparent in pain, fatigue, modified Health Assessment Questionnaire (mHAQ), and Rheumatoid Arthritis Disease Activity Index (RADAI) scores. Conclusions: Improved sleep efficiency and ‘awakening after sleep onset’ time were observed in RA patients treated with anti-TNF-α therapy.

Objectives Poor sleep is increasingly recognized as contributing to a decreased quality of life, increased morbidity/mortality and heightened pain perception. The purpose of the present study was to assess components of sleep quality and self-identified contributors to sleep fragmentation in rheumatoid arthritis (RA) and osteoarthritis (OA) patient populations. Methods Consecutive RA and OA clinic patients were invited to participate in a self-administered questionnaire study which included the validated multi-domain Pittsburgh Sleep Quality Index (PSQI), visual analogue scales for pain, fatigue, global functioning, modified Health Assessment Questionnaire (mHAQ), stress scores, the Centre for Epidemiologic Studies–Depression (CES–D) score, the 36-item short form (SF-36) quality of life measure, the Rheumatoid Arthritis Disease Activity Index (RADAI), the Epworth Sleepiness Scale (ESS), Berlin score for obstructive sleep apnoea (OSA) risk and the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria. Results The study population included 145 RA and 78 OA patients. PSQI global scores were >5 in 62% of RA and 67% of OA patients. Multivariate analysis identified global functioning and the CES–D to be independent predictors for higher global PSQI scores in RA patients, whereas in OA patients predictors were the mHAQ and SF-36 mental component summary. Abnormalities in subjective sleep assessment, sleep latency, sleep duration, sleep efficiency, daytime dysfunction and increased sleep-aid medication use were observed in both populations. The most common abnormality reported by both RA and OA patients was increased sleep fragmentation. The most frequent self-identified cause for sleep disturbance was ‘need to use the washroom’ by 51% of RA and 49% of OA patients, and, second most common, ‘pain’ was identified as a cause for awakening by 33% of RA and 45% of OA patients. Conclusions A high prevalence of abnormal sleep quality in both RA and OA patient populations was observed. The most common abnormality was sleep fragmentation, with an increased sleep disturbance score. ‘Need to use the washroom’ and ‘pain’ were the most common self-identified reasons for awakening from sleep. A review of sleep hygiene, optimization of urological status, and rheumatological disease symptomatic control may prove beneficial in terms of sleep health. Copyright © 2011 John Wiley & Sons, Ltd.

The Spondyloarthritis Research Consortium of Cananda (SPARCC) is a transdiscliplinary research network of investigators interested in spondyloarthritis. The group has been supported by a new research initiative by The Arthritis Society. SPARCC aims to address the genetic basis of susceptibility of the disease and develop and validate clinical and imaging outcomes to assess disease activity and structural damage over time, the response to therapy, and the clinical burden of illness in terms of quality of life and disability. The first step was to develop a database that would allow ascertainment of phenotype for genetic studies, as well as accurate and detailed longitudinal information for disease expression and outcome studies. This article describes the SPARCC database and outlines difficulties and possible solutions for maintaining such a database.

We have previously demonstrated that an oncogenic microRNA miR551b-3p (also known as miR551b) regulates STAT3 transcription thereby enhancing tumor growth and metastasis in ovarian cancer. Herein, we have identified that Oncostatin M (OSM) is upregulated through STAT3-driven transcription, which plays an important role in promoting migration and invasion of breast cancer cells. The purpose of this study was to evaluate the role of miR551b mediated STAT3 activation and the precise mechanism that regulates OSM-Receptor (OSMR) signaling for breast cancer growth and metastasis. MDA-MB231 cells were either overexpressed or silenced with miR551b and anti-miR551b respectively and the effects on proliferation, migration/invasion (Matrigel transwell assay), wound healing and expression of OSMR and its downstream targets (Western blotting, Quantitative RT-PCR) were assessed. Our data demonstrate that miR551b promoted survival, proliferation, invasion and migration and epithelial to mesenchymal transition (EMT) and spheroid formation of breast cancer cells. Our results also show that miR551b-mediated STAT3 activation upregulated the components of OSMR signaling through elevated expression of OSMR, Interleukin 31 receptor-alpha (IL31RA) and their ligands Oncostatin (OSM) and IL31 thereby inducing phosphorylation of STAT3 for tumor cell proliferation, migration and invasion. Conversely, anti-miR551b reduced the expression of OSMR, IL31R and their ligands OSM and IL31 as well as the phosphorylation of STAT3. Briefly, our results provide the first report indicating that miR551b regulates OSMR expression by activating STAT3 and thereby promoting tumor cell growth and metastasis in breast cancer cells through autocrine feed-forward signaling loop. A.G, D.P., contributed equally. Citation Format: Anjali Geethadevi, Deepak Parashar, Miriam Ragle-Aure, Bindu Nair, Yiling Lu, Vessela N. Kristensen, Ming You, Anil K. Sood, Gordon B. Mills, Sunila Pradeep, Pradeep Chaluvally Raghavan. MiR551b-mediated Oncostatin M signaling in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4423.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed medications for the treatment of musculoskeletal disorders. Osteoarthritis is the most common form of arthritis in humans and its prevalence rises with age. Oral NSAIDs have potential associated toxicities that must be monitored for and can limit the use of these drugs in certain populations including people of older age. Topical NSAIDs are now being recognized as an option for the treatment strategy of osteoarthritis. We review the efficacy and safety of one of the most common topical NSAIDS, topical diclofenac, for the treatment of osteoarthritis.

Background: Breast cancer is one of the most common malignancies in women with high mortality rate worldwide. Clinical evidence suggests that antiestrogens have potential to inhibit the progression of hormone-dependent breast cancer. Here we showed that a novel selective estrogen receptor degrader (SERD), EC372, reduced estrogen receptor-α (ER-α), progesterone receptor (PR) and stabilized the expression of ER-β, which resulted in apoptosis in ER-positive breast cancer cells. Methods: We studied the effect of EC372 on DNA damage, cell cycle arrest, apoptosis, epithelial-to-mesenchymal transition (EMT), and mitochondrial membrane potential (MMP) in breast cancer cells. We also performed in vitro assays to evaluate the effect of EC372 on cell proliferation, colony formation, invasion, migration, cell adhesion in 2-dimensional (2-D) and sphere-forming abilities of tumor cells in 3-dimensional (3-D) cultures. Results: Our data show that EC372 inhibited the growth of T47D and MCF-7 human breast cancer cells. EC372 induced apoptosis in both cell lines as marked by cell shrinkage and apoptotic bodies. We found that treatment of EC372 downregulated the levels of ER-α and PR and stabilized the levels of ER-β, which subsequently resulted in cell cycle arrest, apoptosis, and suppressed the growth of breast cancer cells. We have also shown that EC372 reduced cell proliferation, colony formation, 3-D tumor spheroid size, migration, and invasive ability of breast cancer cells. Our cell cycle analysis data indicated that EC372 induced G1 arrest, as evidenced by a decrease in the protein levels of Cyclin D, phospho-Rb (S-807/811), and CDK-6 and increased Rb and p21 levels. We have further shown that EC372 induced apoptosis as evidenced by an increase in the levels of Annexin-V and by upregulation of proapoptotic molecules such as BAK, BAX, BID, cytochrome C, PARP1/cleaved PARP, and caspase 3, with a decrease in the levels of antiapoptotic molecules including BCl2, BCLxL, and survivin. In complement to our results, EC372 reduced the mitochondrial membrane potential (MMP) that triggered the activation of caspase 3 cascade, cleavage of PARP proteins, DNA damage, and subsequent cell death of breast cancer cells. Based on our in vitro results, EC372 is a unique and novel SERD, which inhibits tumor growth, migration, and invasion of breast cancer cells. Studies evaluating the potential of EC372 on in vivo tumor growth and metastasis are under way. Conclusions: This is the first comprehensive study on the mechanism by which EC372 inhibits tumor growth and promotes apoptosis of human breast cancer cells. Our collective data suggest that EC372 inhibits cell growth of ER-positive breast cancer cell lines through downregulating the levels of ER-α and PR, and stabilized the levels of ER-β. Based on our results, we suggest that EC372 is a potent SERD with anticancer effects that could be developed as a novel therapeutic agent to treat ER-positive breast cancer. Citation Format: Deepak Parashar, Anjali Geethadevi, Jyotsna Mishra, Bindu Nair, Bindu Santhamma, Klaus Nickisch, Pradeep Chaluvally-Raghavan. A novel selective estrogen receptor degrader, EC-372, inhibits tumor growth and metastasis of breast cancer cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A195.

Even though birth weight is the most sensitive predictor of health and outcome, accurate weighing and proper recording are not done in most developing countries. Most neonates lose 10% of body weight soon after birth and when such babies subsequently come for medical care, it becomes difficult to know whether the baby was low birth weight (LBW) at birth or not, to predict the outcome. Among the many surrogate auxologic parameters to identify LBW babies, mid arm circumference (MAC) was found to be the most useful and simplest. At a cut off of 9 cm, with a sensitivity of 92% and a specificity of 90.5% to identify LBW, MAC is recommended as an alternative measurement. Ponderal index is measured in neonatal period to identify growth retardation. Body mass index (BMI) is a very useful index in children and adults to identify obesity/chronic energy deficiency (CED). Tracking of BMI from neonatal period to adulthood is recommended to plan intervention and predict outcome. The mean BMI observed in the present study was 12.86 kg/m2 close to the expected of 13.

Various proteins, lipids, or other extracts from human or other animal placentas are described as cosmetic ingredients. Human Placental Protein comprises protein derived from human placentas. Placental Protein is derived from animal placentas. Similarly, Human Placental Lipids and Placental Lipids are the lipid fractions from the same source materials. Hydrolyzed Human Placental Protein and Hydrolyzed Placental Protein are produced from the respective protein extracts by acid, enzyme, or other hydrolysis methods. Human Placental Enzymes and Placental Enzymes are enzymes obtained by aqueous extraction of human or other animal placental material. Human Umbilical Extract and Umbilical Extract are unspecified extracts of material from human or other animal umbilical cords. Different materials called Human Placental Extracts and Placental Extracts, assumed to contain estrogenic hormones or other biologically active substances, are not recognized as cosmetic ingredients, even though the use of these ingredients in cosmetics have been reported to the Food and Drug Administration (FDA). Human-derived ingredients are prohibited from use under the provisions of the European Union cosmetics directive based on concerns about transmission of human spongiform encephalopathies and viral diseases, for example, human immunodeficiency virus (HIV). Umbilical Extract has precedent for unrestricted use in Japan, except for certain products. Most of these ingredients are described as hair-conditioning agents and miscellaneous skin-conditioning agents, although the umbilical extracts function as biological additives in cosmetics. Of the human-derived ingredients, only Human Placental Protein is currently reported to be used. Animal-derived placental proteins, hydrolyzed proteins, lipids, and enzymes were all currently reported to be used. No current uses of the umbilical extracts were reported. Most of the available data relates to placental derivatives that appear to have estrogenic or other biological activity. The one clinical study that appears to utilize proteinaceous material only reported no irritant reaction. Clearly, the available data are insufficient to support safety of these ingredients in cosmetics. The additional data needed include (1) skin sensitization at concentration of use; (2) gross pathology and histopathology in skin and other major organ systems associated with repeated exposures, and dermal reproductive and developmental toxicity data; (3)photosensitization; (4) one genotoxicity assay in a mammalian system; if positive, then a 2-year dermal carcinogenicity study using National Toxicology Program (NTP) methods may be needed; (5) ocular toxicity, if available. Any studies should be done on all ingredients unless chemical analysis data show similarity among ingredients. Because there is confusion and concern about the use of substances with estrogenic or other biological activity in cosmetic formulations, it was concluded that none of these ingredients used in cosmetics should deliver any metabolic/endocrine activity. In addition, any current use of these ingredients should be free of detectable pathogenic viruses or infectious agents.

Background Based on questionnaire criteria, the sensorimotor disorder restless legs syndrome (RLS) has been reported to have a higher prevalence in rheumatoid arthritis (RA) patients than in the general population. There has been some speculation that peripheral arthritic symptoms may allow false positive responses to questionnaire criteria. This study evaluates whether RA patients meeting RLS questionnaire criteria also have objective evidence of increased periodic limb movements (PLMs) characteristic of RLS. Methods Participants were recruited from RA clinic. Questionnaire data collected at study entry included: pain scores, rheumatoid arthritis disease activity index, Epworth sleepiness scale, Pittsburgh sleep quality index and RLS diagnostic criteria. Each participant was provided a PAM-RL actigraphic monitor, which attached to the ankle. This device was worn for two consecutive nights then returned for data download. Laboratory data including hemoglobin, iron studies, renal function and C-reactive protein levels were collected. Results Of the 57 participants, 23 met RLS diagnostic criteria. Those who met RLS criteria demonstrated higher mean frequency of nocturnal PLMs (19.63/hour; SD:21.13) than those who did not meet RLS criteria (11.13/hour; SD:12.10; p = 0.033). There were no significant differences between groups in terms of patient characteristics, disease activity or duration measures. Patients meeting RLS criteria did have poorer sleep quality measures (p

Previously, our electrophysiological studies revealed a transient imbalance between suppressed excitation and enhanced inhibition in hypoglossal motoneurons of rats on postnatal days (P) 12–13, a critical period when abrupt neurochemical, metabolic, ventilatory, and physiological changes occur in the respiratory system. The mechanism underlying the imbalance is poorly understood. We hypothesized that the imbalance was contributed by a reduced expression of brain-derived neurotrophic factor (BDNF), which normally enhances excitation and suppresses inhibition. We also hypothesized that exogenous BDNF would partially reverse this synaptic imbalance. Immunohistochemistry/single neuron optical densitometry, real-time quantitative polymerase chain reaction, and whole-cell patch-clamp recordings were done on hypoglossal motoneurons in brain stem slices of rats during the first three postnatal weeks. Our results indicated that: 1) the levels of BDNF and its high-affinity TrkB receptor mRNAs and proteins were relatively high during the first 1-1½ postnatal weeks, but dropped precipitously at P12–13 before rising again afterwards; 2) exogenous BDNF significantly increased the normally lowered frequency of spontaneous excitatory postsynaptic currents (sEPSCs) but decreased the normally heightened amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) during the critical period; 3) exogenous BDNF also decreased the normally heightened frequency of miniature IPSCs (mIPSCs) at P12–13; and 4) the effect of exogenous BDNF was partially blocked by K252a, a TrkB receptor antagonist. Thus, our results are consistent with our hypothesis that BDNF and TrkB play an important role in the synaptic imbalance during the critical period. This may have significant implications for the mechanism underlying Sudden Infant Death Syndrome (SIDS).

The author writes about her father's illness and how her knowledge of palliative care and "dying with dignity" helped her make important decisions for her father in his last days. She and her family members were able to give him the kind of care he needed and desired. He could enjoy the time he had left, and the family had the satisfaction of serving him when he needed them.

Sodium C14-16 OlefinSulfonate, Sodium C12-14 Olefin Sulfonate, Sodium C 14-18 Olefin Sulfonate, and Sodium C16-18 Olefin Sulfonate are the Sodium α-Olefin Sulfonates used in cosmetics as surfactant-cleansing agents. The highest concentration reportedly is 16% in shampoos and bath and shower products. These ingredients are a mixture of long-chain sulfonate salts prepared by sulfonation of α-olefins of various carbon chain lengths noted as subscripts. In the manufacture of these ingredients, delta and gamma sultones may be produced. Sodium α-Olefin Sulfonates are poorly absorbed through normal skin, but are significantly absorbed through damaged skin. Acute oral LD50 values were 1.3 2.4g/kg in rats and 2.5-4.3 g/kg in mice. Short-term toxicity studies using rats showed no consistent effects, even with exposures in the 0.5-1.0 g/kg range. Concentrations above 10% produced moderate ocular irritation and a concentration of 5% produced mild ocular irritation in rabbits. In reproductive and developmental toxicity studies, fetal abnormalities were noted, but only at doses that were maternally toxic. Genotoxicity data were mostly negative and oral and dermal carcinogenicity studies were negative. Various animal and clinical studies found irritation and sensitization. Sensitization was attributed to low level gamma sultone residues. Because gamma sultones are demonstrated sensitizers at very low levels, it was concluded that any product containing Sodium α-Olefin Sulfonates should have very little gamma sultone residues. The gamma sultone levels should not exceed 10 ppm for saturated (alkane) sultones, 1 ppm for chloro-sultones, and 0.1 ppm for unsaturated sultones. Sodium α-Olefin Sulfonates are otherwise considered safe for use in rinse-off products. Based on concerns about irritation, were Sodium α-Olefin Sulfonates to be used in leave-on products, it was concluded that concentrations should not exceed 2% for such uses.

Polyvinylpyrrolidone (PVP) is a linear polymer of 1-vinyl-2-pyrrolidone monomers used as a binder, emulsion stabilizer, film former, hair fixative, and suspending agent-nonsurfactant. The molecular weight of the polymer ranges from 10,000 to 700,000. PVP K-30, with an average molecular weight of 40,000, is typically used in cosmetic formulations. The highest concentration reported to be used is 35%. There was no significant absorption of PVP K-30 given orally to rats, and the acute oral LD50 was >100 g/kg for rats and guinea pigs. Neither toxic effects nor gross lesions were found in rats maintained for two years on a diet containing 10% PVP K-30. Short-term PVP inhalation studies produced mild lymphoid hyperplasia and fibroplasia in rats, but no inflammatory response. In animal studies, no evidence of significant ocular irritation, skin irritation, or skin sensitization was found at PVP-iodine solution concentrations of 10%. While PVP-iodine is not a cosmetic ingredient, these negative findings were considered to support the safety of the PVP component. Undiluted PVP K-30 was not a dermal irritant or sensitizer in clinical tests. No developmental toxicity was seen in vehicle controls where PVP was used as a vehicle for another agent. In certain assay systems, PVP was genotoxic, but was negative in the majority of studies. Orally administered PVP significantly decreased the rate of bladder tumors in mice exposed to bracken fern. Several studies tested the carcinogenicity of subcutaneous implants of particulate PVP in rats, mice, and rabbits. Although the majority of these studies conducted in rats were positive, tumors (sarcomas) were localized to the site of implantation. Based on the available data, it was concluded that PVP is safe as used in cosmetics.

Mink Oil is obtained from the subdermal fatty tissues of the mink. The oil is a mixture of the natural glycerides of 14-20 carbon chain fatty acids. Mink Oil is used in cosmetic formulations as a hair conditioning agent, an occlusive skin conditioning agent, and as a surfactant. Current data on concentration of use is limited. A Mink Oil cream was noncomedogenic in rabbits following repeated (5 days a week for 2 weeks) applications, although minimal hyperemia and hyperplasia were noted at the treated site toward the end of the treatment. No sensitization was observed in animals treated with Mink Oil under occlusive patches, but sensitization was seen in animals treated with intradermal injections of Mink Oil in a maximization procedure. Mink Oil was not an ocular irritant in animals. Clinical studies done under occlusive patches found no irritation. In another clinical test, a rinse-off product containing 2.8% Mink Oil was applied to the skin for five consecutive days without rinsing. Some erythema was noticed, but in a repeat of the test, no erythema was seen. Mink Oil is reported to provide a minimal sun protection factor (SPF), but did not appear to increase the SPF when added to a solution containing recognized sunscreens. Studies using human volunteers indicate that Mink Oil applied to the skin remains on the skin surface. Additional safety test data are needed, including a 28-day dermal toxicity study, ultraviolet (UV) absorption data (and if the ingredient absorbs in the UVA or UVB region, then photosensitization data are also needed), and method of manufacture (extraction). Independent of these data needs, it is concluded that the total polychlorinated biphenyl (PCB)/pesticide contamination should not exceed 40 ppm with not more than 10 ppm for any specific residue. Because there are additional data needed in order to complete the safety assessment, the overall conclusion is that the available data are insufficient to support the safety of Mink Oil for use in cosmetic products.

This paper pilots an approach to identifying, categorizing, and mapping public land owned by the central, state, and local government in urban developed areas of Ahmedabad, Gujarat, India. The methodology uses information on plot sizes, location, and ownership that is publicly available for all areas covered by town planning schemes. The study examines the extent of unutilized and underutilized public land, which excludes all cemeteries, parks and gardens, heritage buildings, slums, utilities, infrastructure land, and industrial estates. Unused land already earmarked for public purposes were also excluded from the valuation exercise. The potentially marketable land so identified was valued at both official rates and estimated market rates. The value of potentially marketable excess land is significant -- in per capita terms, the high-value scenario substantially exceeds the estimate of total infrastructure investment needs for the next 20 years prepared by an expert committee of the Ministry of Urban Development of the Government of India.

Gelonin is a single chain ribosome inactivating protein (RIP) with potential application in the treatment of cancer and AIDS. Diffraction quality crystals grown using PEG3350, belong to the space group P2(1), with it a = 49.4 Angstrom b = 44.9 Angstrom, c = 137.4 Angstrom and beta = 98.4 degrees, and contain two molecules in the asymmetric unit. Diffraction data collected to 1.8 Angstrom resolution has a R(m) value of 7.3%. Structure of gelonin has been solved by the molecular replacement method, using ricin A chain as the search model. Crystallographic refinement using X-PLOR resulted in a model for which the r.m.s deviations from ideal bond lengths and bond angles are 0.012 Angstrom and 2.7 degrees, respectively The final R-factor is 18.4% for 39,806 reflections for which I > 1.0 sigma(I).The C-alpha atoms of the two molecules in the asymmetric unit superpose to within 0.38 Angstrom for 247 atom pairs. The overall fold of gelonin is similar to that of other RIPs such as ricin A chain and alpha-momorcharin, the r.m.s.d. for C-alpha superpositions being 1.3 and 1.4 Angstrom, respectively The-catalytic residues (Glu166, Arg169 and Tyr113) in the active site form a hydrogen bond scheme similar to that observed in other RIPs. The conformation of Tyr74 in the active site, however, is significantly different from that in alpha-momorcharin. Three well defined water molecules are located in the active site cavity and one of them, X319, superposes to within 0.2 Angstrom of a corresponding water molecule in the structure of alpha-momorcharin. Any of the three could be the substrate water molecule in the hydrolysis reaction catalysed by gelonin.Difference electron density for a N-linked sugar moiety has been observed near only one of the two potential glycosylation sites in the sequence. The amino acid at position 239 has been established as Lys by calculation of omit electron density maps.The two cysteine residues in the sequence, Cys44 and Cys50, form a disulphide bond, and are therefore not available for disulphide conjugation with antibodies. Based on the structure, the region of the molecule that is involved in intradimer interactions is suggested to be suitable for introducing a Cys residue for purposes of conjugation with an antibody to produce useful immunotoxins.

Objectives: There is increasing awareness of the importance of sleep in health maintenance. Our primary objective was to evaluate prevalence of excess daytime sleepiness in a rheumatic disease patient population. Secondary objectives included evaluation of prevalence of abnormal sleep quality and primary sleep disorders. Methods: Consecutive Rheumatology clinic patients were invited to participate in a self-administered questionnaire study. Included were measures for pain, fatigue, and global functioning, modified Health Assessment Questionnaire, Epworth Sleepiness Score (ESS), Pittsburgh Sleep Quality Index (PSQI), Berlin Score, diagnostic criteria for restless legs syndrome (RLS), Centre for Epidemiologic Studies Depression score (CES-D), stress scores, and the short form-36 quality of life instrument. Results: Of 507 consecutive patients invited to participate, 423 agreed. Mean age was 52.1 years; 26% were male. Prevalence of excessive sleepiness (ESS >10) was 25.7%, abnormal sleep quality (PSQI >5) was 67.3%, high risk for obstructive sleep apnea Berlin scores were present in 35.2% and 24% of participants met criteria for RLS. Significantly worse pain, fatigue, global function, short form-36 summary scores, modified Health Assessment Questionnaire, depression, and stress scores were present in patients with higher ESS and PSQI scores. No significant differences in sleep assessment scores were observed between specific rheumatic disease groups. Conclusions: Our findings suggest a high prevalence of unrecognized hypersomnolence, poor sleep quality, and primary sleep disorders in rheumatology patients. We suggest evaluation of sleep health be incorporated into standard clinical assessments of all rheumatology patients. We would recommend this evaluation include the ESS and the criteria for RLS.