The Effect of Bariatric Surgery on Diabetic Retinopathy: Good, Bad, or Both?

Bariatric surgery, initially intended as a weight-loss procedure, is superior to standard lifestyle intervention and pharmacological therapy for type 2 diabetes in obese individuals. Intensive medical management of hyperglycemia is associated with improved microvascular outcomes. Whether or not the reduction in hyperglycemia observed after bariatric surgery translates to improved microvascular outcomes is yet to be determined. There is substantial heterogeneity in the data relating to the impact of bariatric surgery on diabetic retinopathy (DR), the most common microvascular complication of diabetes. This review aims to collate the recent data on retinal outcomes after bariatric surgery. This comprehensive evaluation revealed that the majority of DR cases remain stable after surgery. However, risk of progression of pre-existing DR and the development of new DR is not eliminated by surgery. Instances of regression of DR are also noted. Potential risk factors for deterioration include severity of DR at the time of surgery and the magnitude of glycated hemoglobin reduction. Concerns also exist over the detrimental effects of postprandial hypoglycemia after surgery. In vivo studies evaluating the chronology of DR development and the impact of bariatric surgery could provide clarity on the situation. For now, however, the effect of bariatric surgery on DR remains inconclusive

Water temperature dynamics in High Arctic river basins

Despite the high sensitivity of polar regions to climate change and the strong influence of temperature upon ecosystem processes, contemporary understanding of water temperature dynamics in Arctic river systems is limited. This research gap was addressed by exploring high-resolution water column thermal regimes for glacier-fed and non-glacial rivers at eight sites across Svalbard during the 2010 melt season. Mean water column temperatures in glacier-fed rivers (0.3-3.2 °C) were lowest and least variable near the glacier terminus but increased downstream (0.7-2.3 °C km ). Non-glacial rivers, where discharge was sourced primarily from snowmelt runoff, were warmer (mean: 2.9-5.7 °C) and more variable, indicating increased water residence times in shallow alluvial zones and increased potential for atmospheric influence. Mean summer water temperature and the magnitude of daily thermal variation were similar to those of some Alaskan Arctic rivers but low at all sites when compared with alpine glacierized environments at lower latitudes. Thermal regimes were correlated strongly (p<0.01) with incoming short-wave radiation, air temperature, and river discharge. Principal drivers of thermal variability were inferred to be (i) water source (i.e. glacier melt, snowmelt, groundwater); (ii) exposure time to the atmosphere; (iii) prevailing meteorological conditions; (iv) river discharge; (v) runoff interaction with permafrost and buried ice; and (vi) basin-specific geomorphological features (e.g. channel morphology). These results provide insight into the potential changes in high-latitude river systems in the context of projected warming in polar regions. We hypothesize that warmer and more variable temperature regimes may prevail in the future as the proportion of bulk discharge sourced from glacial meltwater declines and rivers undergo a progressive shift towards snow water and groundwater sources. Importantly, such changes could have implications for aquatic species diversity and abundance and influence rates of ecosystem functioning in high-latitude river systems

Pulse-Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs.

BackgroundNonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.Hypothesis/objectivesThe primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse-administered toceranib phosphate (TOC) combined with lomustine.AnimalsForty-seven client-owned dogs with measurable MCT.MethodsToceranib phosphate was given PO on days 1, 3 and 5 of a 21-day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m(2) . All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.ResultsThe MTD of lomustine was established at 50 mg/m(2) when combined with pulse-administered TOC; the dose-limiting toxicity was neutropenia. Forty-one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression-free survival (PFS) was 53 days (1 to &gt;752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.Conclusions and clinical importanceCombined treatment with pulse-administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT

South African measles outbreak 2009 - 2010 as experienced by a paediatric hospital

Introduction. Between 2009 and 2010, South Africa experienced a major measles outbreak, with more than 18 000 confirmed cases reported to the National Institute of Communicable Diseases.Methods. We studied measles admissions during the outbreak to Red Cross War Memorial Children&#8217;s Hospital, Cape Town, between 1 November 2009 and 31 July 2010. Factors associated with mortality were retrospectively identified from notification record&#160; and hospital admissions data. Multivariate logistic regression was used to investigate potential risk factors for death.Results. In total, 1 861 children were diagnosed with measles; 552 (30%) were admitted to hospital. The most common reason for admission was pneumonia (379 (68%)) and/or diarrhoea (262 (48%)). The median age at admission was 7.36 months (interquartile range (IQR) 5.0 - 10.7). The median duration of admission was 4 days (IQR 2 - 6); total hospital admission time was 3 746 days (10.3 child-years). HIV status was known in 404 (73%) children: 39/400 (14%) were HIV-infected. Eighteen children died (3% of all admissions); 15 (83%) of them were less than 1 year old.In the regression model, HIV-infection (adjusted odds ratio (aOR) 7.55, 95% confidence interval (CI) 2.27 - 25.12) and female sex (aOR 3.86, 95% CI 1.26 - 11.84) were associated with higher odds of death.Conclusions. There was a large paediatric admission burden during the 2009 - 2010 measles outbreak in Cape Town; young children were predominantly affected. HIV-infected children had a significantly higher case fatality

Genetic landscape of autism spectrum disorder in Vietnamese children

Autism spectrum disorder (ASD) is a complex disorder with an unclear aetiology and an estimated global prevalence of 1%. However, studies of ASD in the Vietnamese population are limited. Here, we first conducted whole exome sequencing (WES) of 100 children with ASD and their unaffected parents. Our stringent analysis pipeline was able to detect 18 unique variants (8 de novo and 10 ×-linked, all validated), including 12 newly discovered variants. Interestingly, a notable number of X-linked variants were detected (56%), and all of them were found in affected males but not in affected females. We uncovered 17 genes from our ASD cohort in which CHD8, DYRK1A, GRIN2B, SCN2A, OFD1 and MDB5 have been previously identified as ASD risk genes, suggesting the universal aetiology of ASD for these genes. In addition, we identified six genes that have not been previously reported in any autism database: CHM, ENPP1, IGF1, LAS1L, SYP and TBX22. Gene ontology and phenotype-genotype analysis suggested that variants in IGF1, SYP and LAS1L could plausibly confer risk for ASD. Taken together, this study adds to the genetic heterogeneity of ASD and is the first report elucidating the genetic landscape of ASD in Vietnamese children

New observations on Saturnella saturnus (Steinecke) Fott: the first British record of a little-known enigmatic ‘green’ alga

Saturnella saturnus was discovered in March 2014 in open-water pools on blanket peatland at the Moor House - Upper Teesdale National Nature Reserve, straddling Cumbria and County Durham in NE England. This is the first record for the British Isles of a little-known alga known previously only from a few peat bog areas, mainly in mainland Europe. The literature is reviewed and new observations presented on its morphology and reproduction based on LM examination of living cells. New observations on the chloroplast structure and cytoplasmic inclusions (especially oil droplets) are discussed in relation to the findings of earlier studies. Doubt attaches as whether it is a chlorophyte or a xanthophyte and the identity of small spherical inclusions that have been frequently interpreted as autospores. It occurs in Upper Teesdale in pools that are that are small, relatively newly formed and mostly well-oxygenated. Also discussed is its relationship to Trochiscia, another coloniser of peatland pools. Photographic images are presented for the first time and comments made on its ecology in the context of blanket bog conservation projects and apparent rarity

Experimental evidence that predator range expansion modifies alpine stream community structure

Climate change is projected to facilitate altitudinal range expansions of ‘lowland’ taxa, creating novel species interactions. However, how range shifts will alter biotic interactions and community structure in alpine streams is not well understood. In the Pyrénées, climate-induced physicochemical habitat change is hypothesized to facilitate the colonization of high-altitude streams by Perla grandis, a carnivorous stonefly. A field-based experiment was conducted in mesocosm channels beside a hillslope spring (2000 m asl) in the Taillon-Gabiétous catchment, French Pyrénées. The influence of P. grandis predation on community structure, feeding trait composition, body-size spectrum, and algal chlorophyll a concentration was examined. Gut contents were analyzed and used to identify consumed prey. Total invertebrate density was not significantly reduced by P. grandis, but Baetis spp. densities were depressed in the treatment channels through a combination of direct consumption and predator avoidance (emigration/drift). However, despite fewer grazers in the predator treatment channels, the magnitude of the trophic cascade effect on basal resources (measured as chlorophyll a density) was comparable between treatment and control channels. The results of this experiment suggest that size/species-specific predation, intraguild predation, and interference competition are the likely mechanisms that altered the body-size spectrum in treatment channels. In synergy with climate-driven physicochemical habitat change, the extinction risk of some range-restricted taxa (prey and other predators) could be increased where P. grandis colonization occurs. Hence, conservation efforts are required to ensure that additional anthropogenic stressors (e.g., nutrient enrichment, cattle trampling, hydropower development, ski runs, and tourism) are limited to minimize further pressures on these unique and sensitive habitats

Connectomic Identification and Three-Dimensional Color Tuning of S-OFF Midget Ganglion Cells in the Primate Retina

In the trichromatic primate retina, the “midget” retinal ganglion cell is the classical substrate for red–green color signaling, with a circuitry that enables antagonistic responses between long (L)- and medium (M)-wavelength-sensitive cone inputs. Previous physiological studies showed that some OFF midget ganglion cells may receive sparse input from short (S)-wavelength-sensitive cones, but the effect of S-cone inputs on the chromatic tuning properties of such cells has not been explored. Moreover, anatomical evidence for a synaptic pathway from S cones to OFF midget ganglion cells through OFF midget bipolar cells remains ambiguous. In this study, we address both questions for the macaque monkey retina. First, we used serial block-face electron microscopy to show that every S cone in the parafoveal retina synapses principally with a single OFF midget bipolar cell, which in turn forms a private-line connection with an OFF midget ganglion cell. Second, we used patch electrophysiology to characterize the chromatic tuning of OFF midget ganglion cells in the near peripheral retina that receive combined input from L, M, and S cones. These “S-OFF” midget cells have a characteristic S-cone spatial signature, but demonstrate heterogeneous color properties due to the variable strength of L, M, and S cone input across the receptive field. Together, these findings strongly support the hypothesis that the OFF midget pathway is the major conduit for S-OFF signals in primate retina and redefines the pathway as a chromatically complex substrate that encodes color signals beyond the classically recognized L versus M and S versus L+M cardinal mechanisms

Induction of Anti-Hebbian LTP in CA1 Stratum Oriens Interneurons: Interactions between Group I Metabotropic Glutamate Receptors and M1 Muscarinic Receptors

An anti-Hebbian form of LTP is observed at excitatory synapses made with some hippocampal interneurons. LTP induction is facilitated when postsynaptic interneurons are hyperpolarized, presumably because Ca(2+) entry through Ca(2+)-permeable glutamate receptors is enhanced. The contribution of modulatory transmitters to anti-Hebbian LTP induction remains to be established. Activation of group I metabotropic receptors (mGluRs) is required for anti-Hebbian LTP induction in interneurons with cell bodies in the CA1 stratum oriens. This region receives a strong cholinergic innervation from the septum, and muscarinic acetylcholine receptors (mAChRs) share some signaling pathways and cooperate with mGluRs in the control of neuronal excitability.We therefore examined possible interactions between group I mGluRs and mAChRs in anti-Hebbian LTP at synapses which excite oriens interneurons in rat brain slices. We found that blockade of either group I mGluRs or M1 mAChRs prevented the induction of anti-Hebbian LTP by pairing presynaptic activity with postsynaptic hyperpolarization. Blocking either receptor also suppressed long-term effects of activation of the other G-protein coupled receptor on interneuron membrane potential. However, no crossed blockade was detected for mGluR or mAchR effects on interneuron after-burst potentials or on the frequency of miniature EPSPs. Paired recordings between pyramidal neurons and oriens interneurons were obtained to determine whether LTP could be induced without concurrent stimulation of cholinergic axons. Exogenous activation of mAChRs led to LTP, with changes in EPSP amplitude distributions consistent with a presynaptic locus of expression. LTP, however, required noninvasive presynaptic and postsynaptic recordings

Testing demand responsive shared transport services via agent-based simulations

Demand Responsive Shared Transport DRST services take advantage of Information and Communication Technologies ICT, to provide on demand transport services booking in real time a ride on a shared vehicle. In this paper, an agent-based model ABM is presented to test different the feasibility of different service configurations in a real context. First results show the impact of route choice strategy on the system performance