Online Abuse of UK MPs in 2015 and 2017: Perpetrators, Targets, and Topics

Concerns have reached the mainstream about how social media are affecting political outcomes. One trajectory for this is the exposure of politicians to online abuse. In this paper we use 1.4 million tweets from the months before the 2015 and 2017 UK general elections to explore the abuse directed at politicians. This collection allows us to look at abuse broken down by both party and gender and aimed at specific Members of Parliament. It also allows us to investigate the characteristics of those who send abuse and their topics of interest. Results show that in both absolute and proportional terms, abuse increased substantially in 2017 compared with 2015. Abusive replies are somewhat less directed at women and those not in the currently governing party. Those who send the abuse may be issue-focused, or they may repeatedly target an individual. In the latter category, accounts are more likely to be throwaway. Those sending abuse have a wide range of topical triggers, including borders and terrorism

The Feasibility of a Behavioral Group Intervention after Weight-loss Surgery: A Randomized Pilot Trial

BACKGROUND: Formal psychosocial support programs after weight-loss surgery are limited in scope and availability. OBJECTIVE: This randomized pilot study evaluated the feasibility of a postoperative behavioral intervention program. MATERIALS AND METHODS: Postoperative weight-loss surgery patients (N = 50) were recruited from February 2017-July 2017 and randomized to a four-month behavioral program or usual care wait-list. Outcomes evaluated in addition to feasibility included health-related quality of life (Short Form -36), psychosocial functioning and adherence. Secondary outcomes included within-group changes for each outcome. RESULTS: Out of eight possible sessions, intervention participants attended a mean of 4.2 sessions. Intervention group participants experienced greater improvements in the social functioning domain of health-related quality of life compared to usual care. Self-reported dietary adherence in the intervention group remained stable, while usual care group dietary adherence declined. Within the intervention group, participants also reported gains in the physical function, pain and general health aspects of quality life from baseline to post-treatment. No differences in weight, mood or other eating behaviors (e.g., loss of control, emotional eating) were evident between groups. CONCLUSION: Though participation in a postoperative behavioral intervention varied, the program helped participants to maintain aspects of quality of life and self-reported adherence to dietary recommendations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03092479

A role for the tfs3 ICE-encoded type IV secretion system in pro-inflammatory signalling by the Helicobacter pylori Ser/Thr kinase, CtkA

Two distinct type IV secretion systems (T4SSs) can be identified in certain Helicobacter pylori strains, encoded on mobile genetic elements termed tfs3 and tfs4. Although their function remains unknown, both have been implicated in clinical outcomes of H. pylori infection. Here we provide evidence that the Tfs3 T4SS is required for activity of the pro-inflammatory Ser/Thr kinase protein, CtkA, in a gastric epithelial cell infection model. Previously, purified recombinant CtkA protein has been shown to upregulate NF-kappaB signalling and induce TNF-alpha and IL-8 cytokine secretion from cultured macrophages suggesting that it may potentiate the H. pylori-mediated inflammatory response. In this study, we show that CtkA expressed from its native host, H. pylori has a similar capacity for stimulation of a pro-inflammatory response from gastric epithelial cells. CtkA interaction was found to be dependent upon a complement of tfs3 T4SS genes, but independent of the T4SSs encoded by either tfs4 or the cag pathogenicity island. Moreover, the availability of CtkA for host cell interaction was shown to be conditional upon the carboxyl-terminus of CtkA, encoding a putative conserved secretion signal common to other variably encoded Tfs3 proteins. Collectively, our observations indicate a role for the Tfs3 T4SS in CtkA-mediated pro-inflammatory signalling by H. pylori and identify CtkA as a likely Tfs3 T4SS secretion substrate

Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas

<p>Abstract</p> <p>Background</p> <p>Serum CD26 (sCD26) levels were previously found diminished in colorectal cancer (CRC) patients compared to healthy donors, suggesting its potential utility for early diagnosis. Therefore we aimed to estimate the utility of the sCD26 as a biomarker for CRC and advanced adenomas in a high-risk group of patients. The relationship of this molecule with polyp characteristics was also addressed.</p> <p>Methods</p> <p>sCD26 levels were measured by ELISA in 299 symptomatic and asymptomatic patients who had undergone a colonoscopy. Patients were diagnosed as having no colorectal pathology, non-inflammatory or inflammatory bowel disease, polyps (hyperplastic, non-advanced and advanced adenomas) or CRC.</p> <p>Results</p> <p>At a 460 ng/mL cut-off, the sCD26 has a sensitivity and specificity of 81.8% (95% CI, 64.5-93.0%) and 72.3% (95% CI, 65.0-77.2%) for CRC regarding no or benign colorectal pathology. Clinicopathological analysis of polyps showed a relationship between the sCD26 and the grade of dysplasia and the presence of advanced adenomas. Hence, a 58.0% (95% CI, 46.5-68.9%) sensitivity detecting CRC and advanced adenomas was obtained, with a specificity of 75.5% (95% CI, 68.5-81.0%).</p> <p>Conclusions</p> <p>Our preliminary results show that measurement of the sCD26 is a non-invasive and reasonably sensitive assay, which could be combined with others such as the faecal occult blood test for the early diagnosis and screening of CRC and advanced adenomas. Additional comparative studies in average-risk populations are necessary.</p

Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis

<p>Abstract</p> <p>Background</p> <p>Sitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, is the first in a new class of oral antihyperglycemic agents (AHAs) for the treatment of patients with type 2 diabetes. Type 2 diabetes is a life-long disease requiring chronic treatment and management. Therefore, robust assessment of the long-term safety and tolerability of newer therapeutic agents is of importance. The purpose of this analysis was to assess the safety and tolerability of sitagliptin by pooling 12 large, double-blind, Phase IIb and III studies up to 2 years in duration. Methods: This analysis included 6139 patients with type 2 diabetes receiving either sitagliptin 100 mg/day (N = 3415) or a comparator agent (placebo or an active comparator) (N = 2724; non-exposed group). The 12 studies from which this pooled population was drawn represent the double-blind, randomized, Phase IIB and III studies that included patients treated with the clinical dose of sitagliptin (100 mg/day) for at least 18 weeks up to 2 years and that were available in a single safety database as of November 2007. These 12 studies assessed sitagliptin as monotherapy, initial combination therapy with metformin, or add-on combination therapy with other oral AHAs (metformin, pioglitazone, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone). Patients in the non-exposed group were taking placebo, pioglitazone, metformin, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone. This safety analysis used patient-level data from each study to evaluate clinical and laboratory adverse experiences.</p> <p>Results</p> <p>For clinical adverse experiences, the incidence rates of adverse experiences overall, serious adverse experiences, and discontinuations due to adverse experiences were similar in the sitagliptin and non-exposed groups. The incidence rates of specific adverse experiences were also generally similar in the two groups, with the exception of an increased incidence rate of hypoglycemia observed in the non-exposed group. The incidence rates of drug-related adverse experiences overall and discontinuations due to drug-related adverse experiences were higher in the non-exposed group, primarily due to the increased incidence rate of hypoglycemia in this group. For cardiac- and ischemia-related adverse experiences (including serious events), there were no meaningful between-group differences. No meaningful differences between groups in laboratory adverse experiences, either summary measures or specific adverse experiences, were observed.</p> <p>Conclusion</p> <p>In patients with type 2 diabetes, sitagliptin 100 mg/day was well tolerated in clinical trials up to 2 years in duration.</p

Adenosine and lymphocyte regulation

Adenosine is a potent extracellular messenger that is produced in high concentrations under metabolically unfavourable conditions. Tissue hypoxia, consequent to a compromised cellular energy status, is followed by the enhanced breakdown of ATP leading to the release of adenosine. Through the interaction with A2 and A3 membrane receptors, adenosine is devoted to the restoration of tissue homeostasis, acting as a retaliatory metabolite. Several aspects of the immune response have to be taken into consideration and even though in general it is very important to dampen inflammation, in some circumstances, such as the case of cancer, it is also necessary to increase the activity of immune cells against pathogens. Therefore, adenosine receptors that are defined as ‘sensors–of metabolic changes in the local tissue environment may be very important targets for modulation of immune responses and drugs devoted to regulating the adenosinergic system are promising in different clinical situations

CD26/dipeptidyl peptidase IV (CD26/DPPIV) is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

<p>Abstract</p> <p>Background</p> <p>Design of effective vaccines against the human immunodeficiency virus (HIV-1) continues to present formidable challenges. However, individuals who are exposed HIV-1 but do not get infected may reveal correlates of protection that may inform on effective vaccine design. A preliminary gene expression analysis of HIV resistant female sex workers (HIV-R) suggested a high expression CD26/DPPIV gene. Previous studies have indicated an anti-HIV effect of high CD26/DPPIV expressing cells in vitro. Similarly, high CD26/DPPIV protein levels in vivo have been shown to be a risk factor for type 2 diabetes. We carried out a study to confirm if the high CD26/DPPIV gene expression among the HIV-R were concordant with high blood protein levels and its correlation with clinical type 2 diabetes and other perturbations in the insulin signaling pathway.</p> <p>Results</p> <p>A quantitative CD26/DPPIV plasma analysis from 100 HIV-R, 100 HIV infected (HIV +) and 100 HIV negative controls (HIV Neg) showed a significantly elevated CD26/DPPIV concentration among the HIV-R group (mean 1315 ng/ml) than the HIV Neg (910 ng/ml) and HIV + (870 ng/ml, p < 0.001). Similarly a FACs analysis of cell associated DPPIV (CD26) revealed a higher CD26/DPPIV expression on CD4+ T-cells derived from HIV-R than from the HIV+ (90.30% vs 80.90 p = 0.002) and HIV Neg controls (90.30% vs 82.30 p < 0.001) respectively. A further comparison of the mean fluorescent intensity (MFI) of CD26/DPPIV expression showed a higher DPP4 MFI on HIV-R CD4+ T cells (median 118 vs 91 for HIV-Neg, p = 0.0003). An evaluation for hyperglycemia, did not confirm Type 2 diabetes but an impaired fasting glucose condition (5.775 mmol/L). A follow-up quantitative PCR analysis of the insulin signaling pathway genes showed a down expression of NFκB, a central mediator of the immune response and activator of HIV-1 transcription.</p> <p>Conclusion</p> <p>HIV resistant sex workers have a high expression of CD26/DPPIV in tandem with lowered immune activation markers. This may suggest a novel role for CD26/DPPIV in protection against HIV infection in vivo.</p

Mastectomy versus radiotherapy as treatment for stage I-II breast cancer: A prospective randomized trial at the National Cancer Institute

In 1979, the National Cancer Institute in Bethesda, Maryland initiated a randomized, prospective trial to compare surgery versus radiation therapy in the treatment of stages I and II breast cancer. Surgical treatment consists of total mastectomy with axillary lymph node dissection (modified radical mastectomy) and breast reconstruction; radiation treatment consists of gross tumor excision, axillary lymph node dissection, and comprehensive irradiation including a boost dose to the tumor bed. All patients with pathologically positive axillary nodes receive 11 cycles of adjuvant Adriamycin ® /Cytoxan ® chemotherapy. As of December 1984, there have been 175 patients entered in the study. Twenty-three patients have developed disease recurrence (12 mastectomy, 11 radiation), but it is too early to obtain definitive treatment-related results. En 1979 l'Institut National du Cancer de Bethesda a lancé une étude prospective randomisée permettant de comparer les résultats respectifs de la chirurgie et de la radiothérapie en ce qui concerne les stades I et II du cancer du sein. Le traitement chirurgical consiste en la mastectomie totale complétée par le curage ganglionnaire axillaire (mastectomie totale modifiée); le traitement dit radiothérapique consiste en l'exérèse large de la tumeur associée au curage ganglionnaire axillaire et à l'administration d'une dose élevée de rayons au niveau du lit tumoral. Toutes les opérées dont les ganglions sont envahis reçoivent en outre 11 cycles d'une combinaison d'Adriamycine et Cytoxan. De 1979 à Décembre 1984, 175 malades ont fait l'objet de cette étude. Vingt-trois ont accusé une récidive (12 après mastectomie et 11 après traitement dit radiothérapique) mais il est encore trop tôt pour tirer des conclusions définitives de ces résultats. El Instituto Nacional de Cáncer de Bethesda inició en 1979 un ensayo prospectivo y aleatorio orientado a comparar el tratamiento quirúrgico versus radioterapia en el manejo del cáncer mamario en estados I y II. El tratamiento quirúrgico consistió de mastectomía total con disección ganglionar axilar (mastectomía radical modificada) y reconstrucción mamaria; el manejo radioterapéutico consistió de resección del tumor, disección de los ganglios linfáticos axilares e irradiación comprensiva incluyendo una dosis de refuerzo al lecho tumoral. Todos los pacientes con ganglios axilares histológicamente positivos recibieron 11 ciclos de quimioterapia adyuvante con Adriamicina/Citoxán. Hasta diciembre de 1984, 175 pacientes habían entrado al estudio. Veintitrés pacientes han desarrollado recurrencia de la enfermedad (12 mastectomía, 11 irradiación), pero es todavía muy temprano para derivar resultados definitivos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41319/1/268_2005_Article_BF01655179.pd

Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain

Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naive animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems