Socioeconomic inequalities and type 2 diabetes complications: A systematic review.

BACKGROUND AND OBJECTIVES: A socioeconomic gradient related to type 2 diabetes (T2D) prevalence has been demonstrated in high-income countries. However, there is no evidence of such a socioeconomic gradient regarding diabetes complications. Thus, the aim of this systematic review was to collect data on risk of complications according to socioeconomic status in patients with T2D. METHODS: PubMed and EMBASE were searched for English-language observational studies evaluating the prevalence or incidence of micro- and macrovascular complications according to individual and geographical socioeconomic status (SES). Observational studies reporting the prevalence and risk of micro- and macrovascular diabetes complications, according to an individual or geographical index of deprivation, were selected, and estimated crude and adjusted risks for each complication were reported. RESULTS: Among the 28 included studies, most described a clear relationship between SES and diabetes complications, especially retinopathy (in 9 of 14 studies) and cardiopathy (in 8 of 9 studies). Both individual and area-based low SES was associated with an increased risk of complications. However, very few studies adjusted their analyses according to HbA1c level. CONCLUSION: Evaluation of SES is necessary for every T2D patient, as it appears to be a risk factor for diabetes complications. However, the available studies are insufficient for gradation of the impact of low socioeconomic level on each of these complications. Regardless, strategies for the improved screening, follow-up and care of high-risk patients should now be implemented.

Determinants of 20-year non-progression to Type 2 diabetes in women at very high risk: the E3N cohort study.

AIMS: To identify the most important determinants associated with not developing Type 2 diabetes in women considered to be at very high risk. METHODS: Between 1995 and 2014, we followed 402 women from the E3N cohort study who were considered to be at very high risk of Type 2 diabetes based on the D.E.S.I.R. score. We then computed a classification and regression tree model to identify, among a large set of risk factors, the top risk factors associated with not having Type 2 diabetes at the end of the follow-up. RESULTS: During follow-up, 117 women (29%) were diagnosed with Type 2 diabetes, while 285 (71%) were still free of the disease in 2014. A low Western dietary pattern score was the top characteristic associated with not developing Type 2 diabetes, as only 20% of the women at very high risk in the E3N study with that characteristic developed Type 2 diabetes (compared with 29% overall). In women with a moderate or high Western dietary pattern score, the most important characteristic associated with not developing Type 2 diabetes was a high total dietary antioxidant capacity, as only 26% of these women ultimately developed Type 2 diabetes. CONCLUSIONS: We showed that the top characteristic associated with not developing Type 2 diabetes, despite being at very high risk, was a healthy diet, characterized by limiting Western dietary habits, but with a high intake of antioxidant-rich foods. This underscores the importance of diet in the prevention of Type 2 diabetes in people at high risk.

Dynamics of active subglacial lakes in Recovery Ice Stream.

Recovery Ice Stream has a substantial number of active subglacial lakes that are observed, with satellite altimetry, to grow and drain over multiple years. These lakes store and release water that could be important for controlling the velocity of the ice stream. We apply a subglacial hydrology model to analyze lake growth and drainage characteristics together with the simultaneous development of the ice stream hydrological network. Our outputs produce a good match between modeled lake location and those identified using satellite altimetry for many of the lakes. The modeled subglacial system demonstrates development of pressure waves that initiate at the ice stream neck and transit to within 100 km of the terminus. These waves alter the hydraulic potential of the ice stream and encourage growth and drainage of the subglacial lakes. Lake drainage can cause large R-channels to develop between basal overdeepenings that persist for multiple years. The pressure waves, along with lake growth and drainage rates, do not identically repeat over multiple years, due to basal network development. This suggests that the subglacial hydrology of Recovery Ice Stream is influenced by regional drainage development on the scale of hundreds of kilometers rather than local conditions over tens of kilometers.

The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference 2017.

On March 24 and 25, 2017 researchers and clinicians from around the world met at Temple University in Philadelphia to discuss the current knowledge of Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human disease. The conference was held because of shared concern that MAP is a zoonotic bacterium that poses a threat not only to animal health but also human health. In order to further study this problem, the conferees discussed ways to improve MAP diagnostic tests and discussed potential future anti-MAP clinical trials. The conference proceedings may be viewed on the www.Humanpara.org website. A summary of the salient work in this field is followed by recommendations from a majority of the conferees.

Targeting Complement Pathways During Cold Ischemia and Reperfusion Prevents Delayed Graft Function.

The complement system plays a critical role in ischemia-reperfusion injury (IRI)-mediated delayed graft function (DGF). To better understand the roles of complement activation pathways in IRI in kidney transplantation, donor kidneys were treated ex vivo with terminal complement pathway (TP) inhibitor, anti-rat C5 mAb 18A10, or complement alternative pathway (AP) inhibitor TT30 for 28 h at 4°C pretransplantation in a syngeneic kidney transplantation rat model. All 18A10- and 67% of TT30-pretreated grafts, but only 16.7% of isotype control-pretreated grafts, survived beyond day 21 (p < 0.01). Inhibitor treatment in the final 45 min of 28-h cold ischemia (CI) similarly improved graft survival. Systemic posttransplant treatment with 18A10 resulted in 60% increased graft survival beyond day 21 (p < 0.01), while no TT30-treated rat survived > 6 days. Our results demonstrate that AP plays a prominent role during CI and that blocking either the AP or, more effectively the TP prevents ischemic injury and subsequent DGF. Multiple complement pathways may be activated and contribute to reperfusion injury; blocking the TP, but not the AP, posttransplant is effective in preventing reperfusion injury and increasing graft survival. These results demonstrate the feasibility of using complement inhibitors for prevention of DGF in humans.

Modeling of subglacial hydrological development following rapid supraglacial lake drainage.

The rapid drainage of supraglacial lakes injects substantial volumes of water to the bed of the Greenland ice sheet over short timescales. The effect of these water pulses on the development of basal hydrological systems is largely unknown. To address this, we develop a lake drainage model incorporating both (1) a subglacial radial flux element driven by elastic hydraulic jacking and (2) downstream drainage through a linked channelized and distributed system. Here we present the model and examine whether substantial, efficient subglacial channels can form during or following lake drainage events and their effect on the water pressure in the surrounding distributed system. We force the model with field data from a lake drainage site, 70 km from the terminus of Russell Glacier in West Greenland. The model outputs suggest that efficient subglacial channels do not readily form in the vicinity of the lake during rapid drainage and instead water is evacuated primarily by a transient turbulent sheet and the distributed system. Following lake drainage, channels grow but are not large enough to reduce the water pressure in the surrounding distributed system, unless preexisting channels are present throughout the domain. Our results have implications for the analysis of subglacial hydrological systems in regions where rapid lake drainage provides the primary mechanism for surface-to-bed connections. KEY POINTS: Model for subglacial hydrological analysis of rapid lake drainage eventsLimited subglacial channel growth during and following rapid lake drainagePersistence of distributed drainage in inland areas where channel growth is limited.

Exploring the role of Mycobacterium avium subspecies paratuberculosis in the pathogenesis of type 1 diabetes mellitus: a pilot study.

BACKGROUND: Although the etiology of Type 1 Diabetes mellitus (T1DM) has not been determined, genetic polymorphism in key genes, including SLC11A1, and association with Mycobacterium avium subspecies paratuberculosis (MAP) have been reported. We hypothesize that molecular mimicry between MAP Heat shock protein 65 K (Hsp65) and human Glutamic Acid Decarboxylase 65 K (GAD65) may be the trigger leading to autoimmune destruction of beta cells in patients exposed to MAP. METHOD: Peptide sequences of MAP Hsp65 and human GAD65 were investigated for amino acid sequence homology and cross reactivity. A total of 18 blood samples from T1DM and controls were evaluated for the presence of MAP. RESULTS: Peptide BLAST analysis revealed a 44% overall identity between MAP Hsp65 and GAD65 with 75% positives in a 16 amino acid region. PyMOL 3D-structural analyses identified the same 16 amino acid region as a potential epitope for antibody binding. Preliminary data suggests a cross reactivity between MAP Hsp65, and a healthy rat pancreatic tissue homogenate against plasma from T1DM patients and rabbit polyclonal anti-MAP IgG. Long-term culture of human blood resulted MAP detection in 3/10 T1DM and 4/8 controls whereas MAP IgG was detected in 5/10 T1DM samples and 3/8 non-diabetic controls. CONCLUSION: The high degree of homology between GAD65 and MAP Hsp65 in an antigenic peptide region supports a possible mycobacterial role in triggering autoimmune destruction of pancreatic cells in T1DM. Reactivity of T1DM patient sera with MAP Hsp65 supports this finding. Culture of MAP from the blood of T1DM patients is intriguing. Overall, the preliminary data are mixed and do not exclude a possible role for MAP in T1DM pathogenesis. A larger study including well-characterized controls is needed to investigate the intriguing question of whether MAP is associated with T1DM or not?

Detection of Mycobacterium avium ss. Paratuberculosis in Blau Syndrome Tissues.

Background and Aim of the Work. Blau syndrome is an inherited granulomatous inflammatory disorder with clinical findings of uveitis, arthritis, and dermatitis. Although rare, Blau syndrome shares features with the more common diseases sarcoidosis and Crohn's disease. The clinical findings of Blau syndrome are indistinguishable from juvenile sarcoidosis; the mutations of Blau syndrome are on the same gene of chromosome 16 (CARD15) that confers susceptibility to Crohn's disease. The product of this gene is part of the innate immune system. Mycobacterium avium ss. paratuberculosis (MAP) is the putative cause of Crohn's disease and has been implicated as a causative agent of sarcoidosis. Methods. Archival tissues of individuals with Blau syndrome were tested for the presence of MAP. Results. DNA evidence of MAP was detected in all of the tissues. Conclusions. This article finds that MAP is present in Blau syndrome tissue and postulates that it has a causal role. The presence of MAP in Blau syndrome-an autosomal dominant, systemic inflammatory disease-connects genetic and environmental aspects of "autoimmune" disease.

Cows, Crohn's and more: is Mycobacterium paratuberculosis a superantigen?

The plausibility of a causal role of Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease has gone from controversial to compelling. This century old debate is resolving because of unfolding understanding of shared genetic susceptibilities for Crohn's and mycobacterial infection in addition to newer laboratory tests to detect MAP which have linked MAP and Crohn's. Mycobacterial heat shock proteins are associated with a multitude of "autoimmune" diseases, including Type 1 diabetes mellitus (T1DM) and the initiating events of atherosclerosis. These heat shock proteins may come from MAP; this article postulates a causal role for MAP in multiple inflammatory and "autoimmune" diseases.

Transciliary filtration (Singh filtration) with the Fugo plasma blade.

This article describes plasma blade transciliary filtration for the surgical management of glaucoma in an indigent population. The procedure was found to be safe, effective and straightforward.

Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression.

H. pylori infection accounts for most cases of gastric cancer, but the initiating events remain unclear. The principal H. pylori pathogenicity-associated CagA protein disrupts intracellular SHP-2 signalling pathways including those used by the IL-6 family cytokines, IL-6 and IL-11. Imbalanced IL-6 family cytokine signalling in the gp130(757FF) mouse model of gastric cancer arising from hyperactivation of oncogenic STAT3 after altered SHP-2 : ERK1/2 signalling produces dysplastic antral tumours preceded by gastritis and metaplasia. In a cohort of patient gastric biopsies with known H. pylori and CagA status, we investigated whether (i) STAT3 and ERK1/2 activation is altered in H. pylori-dependent gastritis; (ii) these profiles are more pronounced in CagA+ H. pylori infection; and (iii) the expression of pro-inflammatory cytokines that activate STAT3 and ERK 1/2 pathways is associated with progression to gastric cancer. IL-6, IL-11, and activated STAT3 and ERK1/2 were quantified in antral biopsies from gastritic stomach, metaplastic tissue, and resected gastric cancer tissues. We observed significantly increased STAT3 and ERK1/2 activation (p = 0.001) in H. pylori-dependent gastritis, which was further enhanced in the presence of CagA+ H. pylori strains. Of known gastric ligands that drive STAT3 activation, IL-6 expression was increased after H. pylori infection and both IL-6 and IL-11 were strongly up-regulated in the gastric cancer biopsies. This suggests a mechanism by which IL-11 drives STAT3 activation and proliferation during gastric cancer progression. We addressed this using an in vitro approach, demonstrating that recombinant human IL-11 activates STAT3 and concomitantly increases proliferation of MKN28 gastric epithelial cells. In summary, we show increased STAT3 and ERK1/2 activation in H. pylori-dependent gastritis that is likely driven in an IL-6-dependent fashion. IL-11 expression is associated with adenocarcinoma development, but not gastritic lesions, and we identify a novel mechanism for IL-11 as a potent inducer of proliferation in the human gastric cancer setting.

Paratuberculosis and Type I diabetes: is this the trigger?

Type 1 diabetes mellitus (T1DM) is an autoimmune disease. The etiology of T1DM is incompletely understood but environmental agent(s) are thought to trigger T1DM in the genetically at risk. Exposure to cow's milk early in life is a recognized risk factor in the development of T1DM. Mycobacterium avium ss. paratuberculosis (MAP) is the cause of bovine Johne's disease and also is thought to act as an immune antigen in Crohn's disease and other granulomatous diseases. MAP is shed in cow's milk and has been shown to survive pasteurization. Genetic susceptibilities, epitope homologies and epidemiologic studies are presented that support MAP as a causative agent of T1DM in the genetically at risk.

Components in seminal plasma regulating sperm transport and elimination.

Seminal plasma has been suggested to be involved in sperm transport, and as a modulator of sperm-induced inflammation, which is thought to be an important part of sperm elimination from the female reproductive tract. This article reports on recent experiments on the importance of seminal plasma components in sperm transport and elimination. In Experiment 1, hysteroscopic insemination in the presence (n = 3) or absence (n = 3) of 2 ng/mL PGE showed an increased portion of spermatozoa crossing the utero-tubal junction in the presence of PGE in two mares, while no difference was observed between treatments in a third mare. In Experiment 2, whole seminal plasma, heat-treated seminal plasma (90 degrees C for 45 min), and charcoal-treated seminal plasma were added to: (1) sperm samples during opsonization prior to polymorphonuclear neutrophil(s) (PMN)-phagocytosis assays (n = 5); or to (2) phagocytosis assays (n = 5). Opsonization of spermatozoa was suppressed in the presence of whole seminal plasma, compared with samples without seminal plasma (p < 0.05). Charcoal treatment did not remove the suppressive effect of seminal plasma on opsonization, but heat treatment of seminal plasma reduced its suppressive properties (p < 0.05). The addition of whole seminal plasma to opsonized spermatozoa almost completely blocked phagocytosis (p < 0.05). Charcoal treatment did not remove the suppressive effect of seminal plasma. However, heat-treated fractions of seminal plasma removed the suppressive effect of seminal plasma on phagocytosis (p < 0.05). In Experiment 3, viable and non-viable (snap-frozen/thawed) spermatozoa were subjected to in vitro assays for PMN binding and phagocytosis with the following treatments (n = 3): (1) seminal plasma (SP), (2) extender; (3) ammonium sulfate precipitated seminal plasma proteins with protease inhibitor (SPP+); or (4) ammonium sulfate precipitated seminal plasma proteins without protease inhibitor (SPP-). Treatment was observed to impact binding and phagocytosis of viable and non-viable spermatozoa (p < 0.05). SP and SPP+ suppressed PMN-binding and phagocytosis of viable sperm. This effect was also seen, but to a lesser degree, in SPP- treated samples. Non-viable spermatozoa showed less PMN-binding and phagocytosis than live sperm in the absence of SP. The addition of SP promoted PMN-binding and phagocytosis of non-viable spermatozoa. SPP- treated samples also restored PMN-binding of non-viable spermatozoa. The addition of protease inhibitors removed this effect. In Experiment 4, seminal plasma proteins were fractionated based on MW by Sephacryl S200 HR columns (range 5000-250,000 kDa). Fractionated proteins were submitted to sperm-PMN binding assays. A protein fraction <35 kDa suppressed PMN-binding to live and snap-frozen spermatozoa. A greater MW protein fraction appeared to promote binding between PMNs and snap-frozen spermatozoa. While the addition of protease inhibitors was necessary to maintain the protective effect of seminal plasma proteins on viable spermatozoa, the promotive effect of seminal plasma on non-viable spermatozoa appeared to require some protease activity. It was concluded from these experiments that components of seminal plasma play active roles in transportation and survival of viable spermatozoa in the female reproductive tract and in the elimination of non-viable spermatozoa from the uterus.

Data reduction in headspace analysis of blood and urine samples for robust bacterial identification.

This paper demonstrates the application of chemical headspace analysis to the problem of classifying the presence of bacteria in biomedical samples by using computational tools. Blood and urine samples of disparate forms were analysed using a Cyrano Sciences C320 electronic nose together with an Agilent 4440 Chemosensor. The high dimensional data sets resulting from these devices present computational problems for parameter estimation of discriminant models. A variety of data reduction and pattern recognition techniques were employed in an attempt to optimise the classification process. A 100% successful classification rate for the blood data from the Agilent 4440 was achieved by combining a Sammon mapping with a radial basis function neural network. In comparison a successful classification rate of 80% was achieved for the urine data from the C320 which were analysed using a novel nonlinear time series model.

Hepatic angiosarcoma: detection with computed tomography.

Hepatic angiosarcoma is a rare vascular neoplasm which occurs typically in men aged between 50 and 70 years. The cause is unknown but previous studies have linked several carcinogens to its pathogenesis. A case of advanced multifocal hepatic angiosarcoma with splenic metastasis is presented with brief discussion of the clinical and histological features. Typical CT features and contrast enhancement characteristics are also reviewed.

Cerebellar atrophy in temporal lobe epilepsy affects procedural memory.

The authors examined a cognitive function mediated by the cerebellum, classical eyeblink conditioning, and its relationship to cerebellar volume in healthy controls (n = 59) and temporal lobe epilepsy subjects (n = 77). Controls demonstrated better conditioning, larger cerebellar volumes, and an association between conditioning and cerebellar volume that was not observed in epilepsy patients. These findings provide support for the hypothesis that cerebellar atrophy in epilepsy affects procedural memory.

The nature and course of neuropsychological morbidity in chronic temporal lobe epilepsy.

OBJECTIVE: To characterize the nature and degree of cognitive morbidity in patients with chronic temporal lobe epilepsy compared with healthy control subjects, determine the association between the duration of epilepsy and cognitive morbidity, and ascertain whether there are factors that moderate the association between duration of disorder and cognitive impairment. METHODS: Temporal lobe epilepsy (n = 96) and healthy control (n = 82) subjects were assessed with a comprehensive neuropsychological battery. Test performances were adjusted for age, gender, and education and transformed to a common metric (z scores). Analyses included group comparisons and correlations of duration of epilepsy with cognitive morbidity. RESULTS: Patients with temporal lobe epilepsy exhibited not only worse memory function (p < 0.05) but worse performance across measures of intelligence, language, executive function, and motor speed (p < 0.05). Chronicity of epilepsy was related to worsening mental status (r = 0.42, p < 0.001). This relationship was particularly evident among those individuals with less (r = 0.58, p < 0.001) compared with more (r = 0.25, NS) cerebral reserve, operationally defined by years of formal education. CONCLUSIONS: Neuropsychological morbidity in chronic temporal lobe epilepsy is widespread in nature despite a focal epileptic process. Cross-sectional analyses demonstrate that increasing duration of epilepsy is associated with worsening mental status. Individuals with less educational attainment (low cerebral reserve) exhibit especially poor cognitive function in association with chronicity of epilepsy.

Biliary epithelial trefoil peptide expression is increased in biliary diseases.

AIMS: Maintenance of the cellular integrity of the biliary epithelium may involve the production of mucins and mucin-associated peptides. In the luminal gastrointestinal tract, mucins and the mucin-associated trefoil peptides (TFF) are integral to cytoprotection and cellular repair of the mucosa. METHODS AND RESULTS: Samples of normal and diseased human liver tissue were examined using histological and immunohistochemical techniques, for the expression of TFF and mucins. Bile ducts were classified as small, medium or large depending upon the number of biliary epithelial cells. TFF expression was demonstrated in biliary epithelial cells of both normal and diseased liver tissue. TFF expression was greatest in the large bile ducts. In normal liver tissue, expression of at least one TFF was demonstrated in 2-7% of small bile ducts, 5-31% of medium bile ducts and 31-85% of large bile ducts. Seventy-seven percent of large bile ducts secreted mucins and all three TFF concurrently, compared with 3% of medium bile ducts and no small bile ducts. Biliary disease resulted in an increased expression of TFF1 and TFF3 in the medium bile ducts. CONCLUSIONS: The biliary epithelial cells in normal and diseased human liver tissue express TFF, particularly in the larger bile ducts. TFF expression may be up-regulated or induced in biliary diseases as a response to injury, as is seen in epithelial damage elsewhere in the gastrointestinal tract.