A genome wide association study identifies new genes potentially associated with eyelid sagging

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10^‐10) and rs4746957 (P = 1.06 × 10^‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.     

Differential changes of nicotinic receptors in the ratbrain following ibotenic acid and 192-IgG saporin lesionsof the nucleus basalis magnocellularis

The basal forebrain cholinergic neurons are implicated in the pathogenesis ofneurodegenerative diseases including Alzheimer^fn2s disease (AD). The nicotinic acetylcholine receptors (nAChRs) have been found to besignificantly afflicted in AD. To study the underlying mechanisms for dysfunction of the basalforebrain cholinergic neurons development of suitable animal models is warranted. In this studywe investigated the effects of bilateral lesions of the nucleus basalis magnocellularis on nAChRs inthe rat brain using the cholinergic system selective immunotoxin 192-IgG saporin andnon-selective excitotoxin ibotenic acid. Changes in nAChRs were measured by ³H-cytisineand ³H-epibatidine, two ligands with different selectivity for nAChRs subtypes. Inthe parietal cortex of ibotenic acid lesioned rates, the choline acetyltransferase activity (ChAT)was decreased by 24% while no changes were detected in the frontal cortex or hippocampus.Similarly, a 40% decrease was observed in the number of nAChRs labelled by ³H-cytisine,but not by ³H-epibatidine, in the parietal cortex, while no changes were found in thefrontal cortex or hippocampus. Although the 192-IgG saporin induced lesions reduced the ChATactivity in the frontal cortex, parietal cortex and hippocampus by 77, 50 and 21%, respectively, nochanges were observed in the number of nAChRs as studied by ³H-cytisine or ³H-epibatidine. The results indicate a difference in vulnerability of the cortical nAChRsubtypes to experimental lesions of the nucleus basalis magnocellularis. The findings in this studysuggest that a major portion of the nAChRs might be located on non-cholinergic neurons in thebrain.     

Use of i.v. insulin in well-controlled non-insulin-dependent diabetics undergoing major surgery

We conducted a randomized, prospective study to assess the effect of i.v. insulin on blood glucose control, development of ketone bodies and hormonal changes in 60 well-controlled, non-insulin-dependent diabetics (NIDDM) undergoing major surgery. In group A, patients were given only 0.9% saline; in group B, patients were given insulin as a continuous i.v. infusion (1.25 u. h-1); in group C, patients were given insulin 10 u. i.v. boluses every 2 h. Patients in all three groups were given insulin 5 u. when their intraoperative blood glucose concentration increased to greater than 11.1 mmol litre-1. Blood glucose concentrations were measured every 15 min, from just before induction of anaesthesia to 2 h after surgery. Plasma lactate, pyruvate, ketone body, C-peptide and counter-regulatory hormone concentrations were also measured. Blood glucose concentrations in the three groups did not differ significantly. There was a mild-to-moderate increase in plasma ketone body concentrations in group A, but without any deleterious consequences. Plasma C-peptide concentrations decreased significantly in groups B and C, especially in patients given bolus injections of insulin. Plasma growth hormone concentrations also increased significantly in group B and C patients. This study indicated that the "no insulin--no glucose" regimen was a simple, effective way to control blood glucose in well-controlled NIDDM patients, provided blood glucose was measured frequently and insulin used appropriately.      

Evaluation of whole blood catalase estimation for diagnosis of malignancy

Whole blood catalase levels were estimated using a disc flotation method in 209 random patients with a wide variety of malignancies. Fifty patients had received no treatment, and the remainder, although having undergone prior therapy, had recurrent or metastatic disease at the time of the study. No relationship was found between the presence of cancer and catalase levels. A direct relationship was found for catalase with hemoglobin levels in both normal and patients' samples. Whole blood catalase is of no value in diagnosis and monitoring of cancer. The decreased catalase values found here and reported previously by others are the result of low hemoglobin levels found in many patients with cancer.     

Multivisceral organ failure related to leptospirosis in pregnant patient

Leptospirosis is the most widespread zoonosis in the world. It is caused by pathogenic leptospira infection. This infection is also an uncommon cause of hepatorenal failure. Indeed, hemolysis, elevated liver enzyme levels and low platelet count syndrome, and acute fatty liver of pregnancy are specific to the pregnant state. Leptospirosis is rarely described in pregnancy; it might mimic puerperal sepsis or hepatorenal failure associated with pregnancy induced hypertension. We report a case of leptospirosis presenting as multiple organ failure during third trimester of pregnancy with a good outcome.     

Inlay‐retained cantilever fixed dental prostheses to substitute a single premolar: impact of zirconia framework design after dynamic loading

The purpose of this in‐vitro study was to evaluate the influence of the framework design on the durability of inlay‐retained cantilever fixed dental prostheses (IR‐FDPs), made from zirconia ceramic, after artificial ageing. Forty‐eight caries‐free human premolars were prepared as abutments for all‐ceramic cantilevered IR‐FDPs using six framework designs: occlusal–distal (OD) inlay, OD inlay with an oral retainer wing, OD inlay with two retainer wings, mesial–occlusal–distal (MOD) inlay, MOD inlay with an oral retainer ring, and veneer partial coping with a distal box (VB). Zirconia IR‐FDPs were fabricated via computer‐aided design/computer‐aided manufacturing (CAD/CAM) technology. The bonding surfaces were air‐abraded (50 μm alumina/0.1 MPa), and the frameworks were bonded with adhesive resin cement. Specimens were stored for 150 d in a 37°C water bath during which they were thermocycled between 5 and 55°C for 37,500 cycles; thereafter, they were exposed to 600,000 cycles of dynamic loading with a 5‐kg load in a chewing simulator. All surviving specimens were loaded onto the pontic and tested until failure using a universal testing machine. The mean failure load of the groups ranged from 260.8 to 746.7 N. Statistical analysis showed that both MOD groups exhibited significantly higher failure loads compared with the other groups (i.e. the three OD groups and the VB group) and that there was no significant difference in the failure load among the OD groups and the VB group. In conclusion, zirconia IR‐FDPs with a modified design exhibited promising failure modes.     

Myeloid-derived suppressor cells and regulatory T cells share common immunoregulatory pathways-related microRNAs that are dysregulated by acute lymphoblastic leukemia and chemotherapy

BackgroundRelapse remains a critical challenge in children with acute lymphoblastic leukemia (ALL). The emergence of immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs), and T regulatory (T_reg) cells, has been considered one potential mechanism of relapse in children with ALL.AimThis study aimed to address the microRNAs (miRNAs) related to MDSCs and T_reg cells and to explore their targeted immunoregulatory pathways.MethodsAffymetrix microarray was used for global miRNA profiling in B-ALL pediatric patients before, during, and after induction of chemotherapy. Bioinformatics analysis was performed on MDSCs and T_reg cells-related dysregulated miRNAs, and miR-Pathway analysis was performed to explore their targeted immunoregulatory pathways.Results516 miRNAs were dysregulated in ALL patients as compared to the healthy donor. Among them, 13 miRNAs and 8 miRNAs related to MDSCs and T_reg cells, respectively, were common in all patients. Besides, 12 miRNAs were shared between MDSCs and T_reg cells; 4 of them were common in all patients. Four immune-related pathways; TNF, TGF-β, FoxO, and Hippo were found implicated.ConclusionOur pilot study concluded certain miRNAs related to MDSCs and T_reg cells, these miRNAs were linked to immunoregulatory pathways. Our results open avenues for testing those miRNA as molecular biomarkers for the immunosuppressive tumor microenvironment.