In vivo Expansion of Naïve CD4+CD25high FOXP3+ Regulatory T Cells in Patients with Colorectal Carcinoma after IL-2 Administration

Regulatory T cells (Treg cells) are increased in context of malignancies and their expansion can be correlated with higher disease burden and decreased survival. Initially, interleukin 2 (IL-2) has been used as T-cell growth factor in clinical vaccination trials. In murine models, however, a role of IL-2 in development, differentiation, homeostasis, and function of Treg cells was established. In IL-2 treated cancer patients a further Treg-cell expansion was described, yet, the mechanism of expansion is still elusive. Here we report that functional Treg cells of a naïve phenotype - as determined by CCR7 and CD45RA expression - are significantly expanded in colorectal cancer patients. Treatment of 15 UICC stage IV colorectal cancer patients with IL-2 in a phase I/II peptide vaccination trial further enlarges the already increased naïve Treg-cell pool. Higher frequencies of T-cell receptor excision circles in naïve Treg cells indicate IL-2 dependent thymic generation of naïve Treg cells as a mechanism leading to increased frequencies of Treg cells post IL-2 treatment in cancer patients. This finding could be confirmed in naïve murine Treg cells after IL-2 administration. These results point to a more complex regulation of Treg cells in context of IL-2 administration. Future strategies therefore might aim at combining IL-2 therapy with novel strategies to circumvent expansion and differentiation of naïve Treg cells

Facilitating health and wellbeing is "everybody's role": youth perspectives from Vanuatu on health and the post-2015 sustainable development goal agenda

BACKGROUND: Progress towards achievement of the Millennium Development Goals (MDGs) amongst Pacific island countries (PICs) has seen mixed results. As focus shifts to formulation of new health-related development goals beyond 2015, there is a need for bringing community consultation into this process. For this purpose, Go4Health is a global consortium examining the development of these goals, with Work Package 2 capturing viewpoints of marginalised populations regarding health. This paper examines the perspectives of youth in Vanuatu on essential health needs in the context of the post-2015 development agenda, to make these concerns more visible for their communities, stakeholders and health policy decision makers. METHODS: As part of a larger investigation undertaken in Vanuatu involving 100 residents from various rural and urban communities, this paper explores the perspectives of twenty 17-year old secondary school students gathered through two focus group discussions during September 2013. Questions sought viewpoints across areas including health ideals, essential needs, responsibility for health services and their governance. Focus group discussions were conducted in English and digitally recorded, with resulting transcripts subjected to thematic analysis. RESULTS: This youth cohort from Vanuatu had a strong understanding of the social determinants of health. They placed value on all aspects of health, indicating the need for youth to have access to positive lifestyle opportunities (sport, community participation) and also increased protection from the impact of harmful substances and causes of chronic illness. Participants identified barriers to health due to unevenly distributed health services throughout Vanuatu, with members at all levels of society ultimately perceived as responsible for improving health throughout the nation. CONCLUSION: Against a background of a weak health system and significant challenges to public health, young people are acutely aware that improving Vanuatu’s health status requires a communal effort. While contributing factors to health depend on actions taken at individual, local, national and global levels, no single actor currently provides enough support to cover all essential health needs. As a consequence, they see health in the Pacific as “everybody’s role”, of importance for the post-2015 sustainable development goal agenda and health policy makers in general

Trends in the incidence of primary liver cancer in Central Uganda, 1960–1980 and 1991–2005

Primary liver cancer (PLC) incidence trends from Africa are unknown. Using Kampala Cancer Registry data from 1960 to 1980 and 1991 to 2005, we identified 771 PLCs. Although rates were stable among men, PLC incidence among women increased >50%. Investigations of viral hepatitis, aflatoxin, obesity, and human immunodeficiency virus (HIV) may help to explain the increasing incidence of hepatocellular carcinomas (HCCs)

Dipeptidyl peptidase IV inhibitor attenuates kidney injury in rat remnant kidney

BACKGROUND: The inhibition of dipeptidyl peptidase (DPP) IV shows protective effects on tissue injury of the heart, lung, and kidney. Forkhead box O (FoxO) transcriptional factors regulate cellular differentiation, growth, survival, the cell cycle, metabolism, and oxidative stress. The aims of this study were to investigate whether the DPP IV inhibitor sitagliptin could attenuate kidney injury and to evaluate the status of FoxO3a signaling in the rat remnant kidney model. METHODS: Rats were received two-step surgery of 5/6 renal mass reduction and fed on an oral dose of 200 mg/kg/day sitagliptin for 8 weeks. Before and after the administration of sitagliptin, physiologic parameters were measured. After 8 weeks of treatment, the kidneys were harvested. RESULTS: The sitagliptin treatment attenuated renal dysfunction. A histological evaluation revealed that glomerulosclerosis and tubulointerstitial injury were significantly decreased by sitagliptin. Sitagliptin decreased DPP IV activity and increased the renal expression of glucagon-like peptide-1 receptor (GLP-1R). The subtotal nephrectomy led to the activation of phosphatidylinositol 3-kinase (PI3K)-Akt and FoxO3a phosphorylation, whereas sitagliptin treatment reversed these changes, resulting in PI3K-Akt pathway inactivation and FoxO3a dephosphorylation. The renal expression of catalase was increased and the phosphorylation of c-Jun N-terminal kinase (JNK) was decreased by sitagliptin. Sitagliptin treatment reduced apoptosis by decreasing cleaved caspase-3 and −9 and Bax levels and decreased macrophage infiltration. CONCLUSIONS: In rat remnant kidneys, DPP IV inhibitor attenuated renal dysfunction and structural damage. A reduction of apoptosis, inflammation and an increase of antioxidant could be suggested as a renoprotective mechanism together with the activation of FoxO3a signaling. Therefore, DPP IV inhibitors might provide a promising approach for treating CKD, but their application in clinical practice remains to be investigated

Chromosome 1p36 in migraine with aura: association study of the 5HT(1D) locus.

Migraine with aura (MA) may share some but not all risk factors with other forms of migraine. As common migraine without aura (MO) has been associated with the chromosome 1p36 locus, we tested its involvement in MA by using two-point parametric linkage analysis to analyze 64 multiplex MA families. A logarithm of the odds score of 1.9 was suggestive of chromosome 1p36 linkage to MA. The transmission disequilibrium test analysis was then performed in 79 nuclear families with one MA parent and one MA offspring. We identified the presence of genetic association at chromosome 1p36 with MA (P=0.045, Bonferroni corrected): the locus encoding the 5HT(1D) receptor gene. Although these data suggest that the 1p36 locus may protect against MA, consistent with the role of the 5HT(1D) receptor in migraine treatment with triptan drugs, the study is subject to the limitations associated with studying a small number of affected families. As a result, we contrast evidence suggesting that the chromosome 1p36 locus is strongly MO associated with our finding that 1p36 has a more limited contribution to MA in the families we analyzed. Further work using a genome-wide association study approach in familial typical migraine, consisting of those affected by MO or MA, will serve to further distinguish how and why MA differs from MO

The effectiveness of extracorporeal shock wave therapy in snapping scapula

© Journal of Orthopaedic Surgery 2017.Background: Bursitis of the snapping scapula is commonly a misdiagnosed problem. Extracorporeal shockwave therapy (ESWT) has been used successfully in the treatment of many chronic inflammatory conditions. The aim of this study was to assess and compare the effectiveness of ESWT in the treatment of scapulothoracic bursitis with the outcome of corticosteroid injection. Methods: Using the randomized controlled trials 43 patients with scapulothoracic bursitis were divided into two groups. Group 1 (n = 22) received three sessions of ESWT. Group 2 (n = 21) received a single local injection of 80 mg of methylprednisolone. Visual analogue scale (VAS) scores were recorded at each follow-up, whereas the level of satisfaction was evaluated using the Roles and Maudsley criteria. Results: In group 1, the average VAS scores after 1, 2, 3, and 6 months were 39, 30, 27, and 16, respectively, whereas, in group 2, the average VAS scores were 46, 44, 35, and 36, respectively. There was no statistical significance between the two groups in the first and second months. However, after 3 and 6 months, group 1 revealed lower average VAS scores compared to that of the second group with p-values (0.012 and 0.001), respectively. Roles and Maudsley criteria showed that first group patients were 46% excellent, 36% good, 14% acceptable, and 4% had poor results. However, second group patients were 24% excellent, 33% good, 19% acceptable, and 24% had poor results. Conclusion: We believe that ESWT is a beneficial and trustable method of treatment and can be strongly recommended in painful cases of scapulothoracic bursitis