Improving asthma outcomes in harder-to-reach populations: challenges for clinical and community interventions

The burden of asthma differs from country to country and within populations. The factors that influence this variation include asthma prevalence and severity, aspects of healthcare services (such as accessibility, quality and utilisation) and social demographic factors (such as income inequality, cultural and linguistic diversity and indigenous populations). The identification of individuals and populations that are 'harder to reach', 'special' or at greater risk of poor asthma outcomes therefore depends on how the burden of asthma and its management are measured. Meeting the challenge of educating harder-to-reach populations with asthma is the focus of this article. In clinical settings, communication is the mainstay of engaging and building trust to influence behavioural change in individuals; community-based interventions provide valuable opportunities for targeting harder-to-reach populations. However, they require active community consultation and participation and innovative approaches to service delivery, in addition to being theoretically driven and systematically developed.     

11beta-alkyl-Delta9-19-nortestosterone derivatives: high-affinity ligands and potent partial agonists of the androgen receptor

We report the synthesis of novel steroidal androgen receptor ligands comprising 11beta-alkyl-Delta(9)-derivatives of 19-nortestosterone. These compounds are structurally related to the antiprogestin, antiglucocorticoid, and antiandrogen drug mifepristone (RU486). Nortestosterone analogues bearing 11beta-octyl and 11beta-decyl side-chains bind tightly to recombinant AR protein (IC(50) = 6.6 nM and IC(50) = 0.8 nM), block AR dimerization, exhibit activity against LNCaP prostate cancer cells, and comprise partial AR agonists with low antiglucocorticoid activity.     

Evaluation of familial influences on the course and severity of schizophrenia among US and Indian cases

Abstract.Background: Prior studies suggest familial (possibly genetic) influences on the course of schizophrenia.Aims: The aim of this study was to compare familial influences on the course and severity of schizophrenia in two independent samples.Method: Thirteen selected measures were compared among affected sibling pairs (ASPs) from Pittsburgh, USA and New Delhi, India (48 US pairs, 53 Indian pairs). For each ASP proband, an unrelated patient was selected randomly from a suitable pool of cases ascertained in the same study (Sibpair proband—comparison case or S-C pairs). Correlations between these pairs were compared.Results: The correlations varied by item and by site. Significant correlations for longitudinal course and pattern of severity were noted among the ASPs from USA, but did not remain significant following corrections for multiple comparisons. Comparisons between the correlations for ASPs and the S-C pairs, used to estimate familial effects, yielded trends for the ASP correlations to be numerically larger than the S-C correlations in both samples. Separate cross-site comparisons revealed several significant differences with regard to several demographic and clinical variables. The possible impact of the cross-site variations on the observed ASP correlations is discussed.Conclusions: Though familial factors did not appear to have a significant impact on course/severity using this novel design, the suggestive trends need to be examined in larger samples.     

Dynamics of CD4 and CD8 T cell responses to cytomegalovirus in healthy human donors

To study the dynamics of cytomegalovirus (CMV) immunity in healthy immunocompetent hosts, interferon-gamma-producing CD4 and CD8 T cell responses in the presence or absence of CMV antigens were measured from 15 CMV-seropositive donors and 13 CMV-seronegative donors. Cytokine responses in the absence of antigen were significantly higher in CMV-seropositive donors. Also, a disproportionate number of CD69(+) cells isolated ex vivo from CMV-seropositive donors were specific for CMV, suggesting recent reactivation in vivo. To examine changes in cellular responses over time, 10 seropositive donors were tested over a 6-month period. About half of the donors showed significant variability over time, but staphylococcal enterotoxin B responses remained relatively constant. These findings suggest that CMV can present a considerable and recurrent burden to the human immune system. By understanding the normal dynamics of CMV responses over time, it may be possible to better identify aberrant responses to CMV in immunocompromised hosts.     

Infection with Bartonella weissii and detection of Nanobacterium antigens in a North Carolina beef herd

Very recently, Bartonella organisms have been isolated from large ruminants (deer, elk, and dairy and beef cattle) located in the United States and in France. In this study, we report the serologic, microbiologic, and molecular findings related to the isolation of a Bartonella species in North Carolina beef cattle and the detection of nanobacterial antigen using a commercially available enzyme-linked immunosorbent assay. Between August 1998 and September 1999, blood was collected from 38 cattle ranging in age from 1 month to 6.5 years. After a 1-month incubation period, a Bartonella sp. was isolated on a 5% rabbit blood agar plate from three of six EDTA blood samples. PCR amplification of the 16S rRNA gene from all three isolates resulted in a DNA sequence that was 100% identical to that of B. weissii 16S rRNA (GenBank no. AF199502). By IFA testing, 36 of 38 cattle had antibodies (> or =1:64) to Bartonella weissii (bovine origin) antigens. Nanobacterial antigen was detected in 22 of 22 serum samples. We conclude that infection with an organism similar or closely related to B. weissii can occur in North Carolina cattle and that although their actual existence is still controversial Nanobacterium antigens were detected with a commercially available test kit. The epidemiology, vector biology, and potential pathogenicity of these organisms in cattle deserve future consideration.     

“It’s Not JUST Skin Cancer”: Understanding Their Cancer Experience From Melanoma Survivor Narratives Shared Online

Cancer survivors narrate their experiences in unique ways, articulating different aspects of the cancer journey. The purpose of this study was to analyze the content of cancer narratives that melanoma survivors share online in order to present the ways that survivors narrate their cancer experience, to identify survivors’ motivations for sharing, and to better understand the ways in which survivors are impacted by and cope with the diagnosis and treatment of cancer. The sample consisted of 95 unique melanoma survivor narratives, accessed from the Melanoma Research Foundation in November 2015, that were inductively and deductively coded for key themes and subthemes. Emergent themes described different aspects of the melanoma experience during prediagnosis (identification of self-phenotype, searching for causes, suspicious findings, delay in diagnosis), diagnosis (communication of diagnosis, emotional responses), transition from diagnosis to beginning treatment (second opinion), treatment (positive reframing of attitude, proactive cancer management, side effects), and posttreatment phases (social support, vigilance behaviors posttreatment). Two themes that cut across all phases of the cancer journey included recognizing and dealing with uncertainty and survivors’ motive for sharing narrative. These findings have implications for understanding how melanoma survivors may benefit personally from sharing their cancer experience online and for the potential for survivor narratives to motivate behavior change and facilitate coping among readers.     

Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Design, synthesis and evaluation of N-acetyl glucosamine (NAG)-PEG-doxorubicin targeted conjugates for anticancer delivery

Efficacy of anticancer drug is limited by the severe adverse effects induced by drug; therefore the crux is in designing delivery systems targeted only to cancer cells. Toward this objectives, we propose, synthesis of poly(ethylene glycol) (PEG)-doxorubicin (DOX) prodrug conjugates consisting N-acetyl glucosamine (NAG) as a targeting moiety. Multicomponent system proposed here is characterized by (1)H NMR, UV spectroscopy, and HPLC. The multicomponent system is evaluated for in vitro cellular kinetics and anticancer activity using MCF-7 and MDA-MB-231 cells. Molecular modeling study demonstrated sterically stabilized conformations of polymeric conjugates. Interestingly, PEG-DOX conjugate with NAG ligand showed significantly higher cytotoxicity compared to drug conjugate with DOX. In addition, the polymer drug conjugate with NAG and DOX showed enhanced internalization and retention effect in cancer cells, compared to free DOX. Thus, with enhanced internalization and targeting ability of PEG conjugate of NAG-DOX has implication in targeted anticancer therapy.