Double Heterozygous Mutations Involving Both HNF1A/MODY3 and HNF4A/MODY1 Genes: A case report

none9Abstract We describe the first MODY case with mutations involving both HNF4A and HNF1A genes. History and Examination. A male patient was diagnosed with diabetes at age 17; the metabolic control rapidly worsened to insulin requirement. At that time no relatives were known to be affected by diabetes, which was diagnosed years later in both parents (father at age 50, mother at age 54) and the sister (age 32 during pregnancy). Investigations. The genetic screening showed a double heterozygosity for the mutation p.E508K in HNF1A/MODY3 gene and the novel variant p.R80Q in HNF4A/MODY1 gene. The genetic testing of the family showed that the father carried the MODY3 mutation while the mother, the sister and her two children carried the MODY1 mutation. Conclusions. MODY1 and MODY3 mutations may interact by chance to give a more severe form of diabetes (younger age at presentation, early need of insulin therapy to control hyperglycemia).mixedG. Forlani; S. Zucchini; A. Di Rocco; R. Di Luzio; M. Scipione; E. Marasco; G. Romeo; G. Marchesini Reggiani; V. MantovaniG. Forlani; S. Zucchini; A. Di Rocco; R. Di Luzio; M. Scipione; E. Marasco; G. Romeo; G. Marchesini Reggiani; V. Mantovan

GM1 ganglioside-independent intoxication by Cholera toxin

Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors via its B subunit (CTB). We have recently shown that in addition to the previously described binding partner ganglioside GM1, CTB binds to fucosylated proteins. Using flow cytometric analysis of primary human jejunal epithelial cells and granulocytes, we now show that CTB binding correlates with expression of the fucosylated Lewis X (LeX) glycan. This binding is competitively blocked by fucosylated oligosaccharides and fucose-binding lectins. CTB binds the LeX glycan in vitro when this moiety is linked to proteins but not to ceramides, and this binding can be blocked by mAb to LeX. Inhibition of glycosphingolipid synthesis or sialylation in GM1-deficient C6 rat glioma cells results in sensitization to CT-mediated intoxication. Finally, CT gavage produces an intact diarrheal response in knockout mice lacking GM1 even after additional reduction of glycosphingolipids. Hence our results show that CT can induce toxicity in the absence of GM1 and support a role for host glycoproteins in CT intoxication. These findings open up new avenues for therapies to block CT action and for design of detoxified enterotoxin-based adjuvants

A metabarcoding analysis of the wrackbed microbiome indicates a phylogeographic break along the North Sea–Baltic Sea transition zone

Sandy beaches are biogeochemical hotspots that bridge marine and terrestrial ecosystems via the transfer of organic matter, such as seaweed (termed wrack). A keystone of this unique ecosystem is the microbial community, which helps to degrade wrack and re-mineralize nutrients. However, little is known about this community. Here, we characterize the wrackbed microbiome as well as the microbiome of a primary consumer, the seaweed fly Coelopa frigida, and examine how they change along one of the most studied ecological gradients in the world, the transition from the marine North Sea to the brackish Baltic Sea. We found that polysaccharide degraders dominated both microbiomes, but there were still consistent differences between wrackbed and fly samples. Furthermore, we observed a shift in both microbial communities and functionality between the North and Baltic Sea driven by changes in the frequency of different groups of known polysaccharide degraders. We hypothesize that microbes were selected for their abilities to degrade different polysaccharides corresponding to a shift in polysaccharide content in the different seaweed communities. Our results reveal the complexities of both the wrackbed microbial community, with different groups specialized to different roles, and the cascading trophic consequences of shifts in the near shore algal community

Urinary C-Peptide Creatinine Ratio Is a Practical Outpatient Tool for Identifying Hepatocyte Nuclear Factor 1-α/Hepatocyte Nuclear Factor 4-α Maturity-Onset Diabetes of the Young From Long-Duration Type 1 Diabetes

Hepatocyte nuclear factor 1-α (HNF1A)/hepatocyte nuclear factor 4-α (HNF4A) maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 diabetes, and patients are inappropriately treated with insulin. Blood C-peptide can aid in the diagnosis of MODY, but practical reasons limit its widespread use. Urinary C-peptide creatinine ratio (UCPCR), a stable measure of endogenous insulin secretion, is a noninvasive alternative. We aimed to compare stimulated UCPCR in adults with HNF1A/4A MODY, type 1 diabetes, and type 2 diabetes.RD&E staff can access the full-text of this article via OpenAthens. Click on the 'Additional Link' above to access the full-text and log in with NHS OpenAthens if prompted.PDA/02/06/098/Department of Health/United Kingdo

The EUFOREA pocket guide for chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS

Legacy Effects of Canopy Disturbance on Ecosystem Functioning in Macroalgal Assemblages

Macroalgal assemblages are some of the most productive systems on earth and they contribute significantly to nearshore ecosystems. Globally, macroalgal assemblages are increasingly threatened by anthropogenic activities such as sedimentation, eutrophication and climate change. Despite this, very little research has considered the potential effects of canopy loss on primary productivity, although the literature is rich with evidence showing the ecological effects of canopy disturbance. In this study we used experimental removal plots of habitat-dominating algae (Order Fucales) that had been initiated several years previously to construct a chronosequence of disturbed macroalgal communities and to test if there were legacy effects of canopy loss on primary productivity. We used in situ photo-respirometry to test the primary productivity of algal assemblages in control and removal plots at two intertidal elevations. In the mid tidal zone assemblage, the removal plots at two sites had average primary productivity values of only 40% and 60% that of control areas after 90 months. Differences in productivity were associated with lower biomass and density of the fucoid algal canopy and lower taxa richness in the removal plots after 90 months. Low-shore plots, established three years earlier, showed that the loss of the large, dominant fucoid resulted in at least 50% less primary productivity of the algal assemblage than controls, which lasted for 90 months; other smaller fucoid species had recruited but they were far less productive. The long term reduction in primary productivity following a single episode of canopy loss of a dominant species in two tidal zones suggests that these assemblages are not very resilient to large perturbations. Decreased production output may have severe and long-lasting consequences on the surrounding communities and has the potential to alter nutrient cycling in the wider nearshore environment

Rhinitis in the geriatric population

The current geriatric population in the United States accounts for approximately 12% of the total population and is projected to reach nearly 20% (71.5 million people) by 2030[1]. With this expansion of the number of older adults, physicians will face the common complaint of rhinitis with increasing frequency. Nasal symptoms pose a significant burden on the health of older people and require attention to improve quality of life. Several mechanisms likely underlie the pathogenesis of rhinitis in these patients, including inflammatory conditions and the influence of aging on nasal physiology, with the potential for interaction between the two. Various treatments have been proposed to manage this condition; however, more work is needed to enhance our understanding of the pathophysiology of the various forms of geriatric rhinitis and to develop more effective therapies for this important patient population