Hybrid closed Loop improved glucose control compared to sensor-augmented pumps in outpatients with type 1 diabetes in real-life conditions with telehealth monitoring.

OBJECTIVES: The study aims at evaluating glucose metrics and HbA1C values after pump initiation in outpatient settings. RESEARCH DESIGN AND METHODS: This single center observational study enrolled 121 subjects with type 1 diabetes between September 2020 and May 2021 initiating sensor-augmented pump therapy with stand-alone CGM (n = 26) or pump users who only changed their device (n = 51), with predictive low glucose management (n = 8) or with Hybrid Closed Loop using Medtronic 780G (n = 36) systems. Changes in HbA1C levels and glucose metrics were analyzed after 3 months. All subjects received diabetes and carbohydrate-counting education if needed at time of initiation and were proposed a telehealth monitoring by a diabetic nurse educator. RESULTS: There was no episodes of severe hypoglycemia or diabetic ketoacidosis nor serious pump-related adverse events despite outpatient model of care. While only 18/121 (14.8%) participants reached initially the recommended HbA1C levels, 23/85 (27%) in the conventional group and 33/36 (91%) subjects in the Hybrid Closed Loop group reached target levels after 3 months of follow-up. Time in target range 3.9-10 mmol/L (70-180 mg/dl) also improved and was optimal with closed loop with 30/36 (83%) subjects with time in range above 70%. CONCLUSIONS: Initiation of insulin pump therapy for outpatients is safe with a dedicated facility. Telehealth monitoring after outpatient initiation provides tools for improvement in glucose control with an insulin pump. Outpatient pump initiation is compatible with Hybrid Closed Loop systems which provide the largest improvements in glucose control.

Determinants of the intention to use condoms in a sample of French adolescents.

OBJECTIVE: To identify the determinants of the intention to use and actual use of condoms in a sample of French adolescents based on Ajzen's Theory of Planned Behaviour. METHOD: Two-hundred-and-thirty French secondary-school students (mean age: 17.68 years; SD = 1.08) completed a questionnaire about condom use intention. RESULTS: 'Perceived behavioural control', 'individual attitudes', 'subjective socio-cultural norms' and 'subjective norms of close friends and relatives' are the main factors explaining 33% of variance of condom use intention. For girls, intention is essentially associated with perceived control, subjective norms ('close friends and relatives', and then, 'socio-cultural norms') and individual attitudes, whereas for boys, it is more closely linked to individual attitudes and to subjective socio-cultural norms. The best predictors of the intention to use a condom are perceived control and individual attitudes for girls while, for boys, individual attitudes come before perceived control. CONCLUSION: In order to design effective programmes for prevention of sexually transmitted infections, the determinants of the intention to use condoms must be considered.

Severe hypertriglyceridaemia in Type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency.

AIMS/HYPOTHESIS: Hypertriglyceridaemia is common in Type II (non-insulin-dependent) diabetes mellitus. Only subgroups of patient however have type V hyperlipidaemia. To investigate the coordination between genetic factors in the modulation of hypertriglyceridaemia in Type II diabetes, we studied three major modifier loci: apoC-III (both Sst-I and insulin-responsive element polymorphisms), apolipoprotein E genotypes and lipoprotein-lipase mutations. METHODS: We studied apoCIII gene polymorphisms, apolipoprotein E genotypes and lipoprotein-lipase gene mutations in 176 patients with Type II (non-insulin-dependent) diabetes mellitus, either normolipaemic (group N, n = 116), mildly hypertriglyceridaemic (group T, n = 28) or with a history of severe hypertriglyceridaemia (triglyceride > 15 g/l) (group H, n = 32). RESULTS: Mild hypertriglyceridaemia in Type II diabetes did not associate with any gene variants in this study. Severe hypertriglyceridaemia was, however, associated with the presence of the apoC-III S2 allele (50% of the patients in group H compared with 15.5 % in group N, p < 0.0001). Additionally this particular phenotype was associated with a low prevalence of the apo E3 allele (35.9% in group H vs 18.1 % in group N, p < 0.005) and a statistically significant over-representation of the E2E4 genotypes. Inactivating lipoprotein-lipase mutations were found in four patients (three heterozygotes, one homozygote), none was found in group N or T. Thus 68.7 % of group H patients (22/32) (vs 21.4 % in group T, p < 0.0005) were carriers of either S2 allele, lipoprotein-lipase mutants or E2E4 genotype with most lipoprotein-lipase mutants or E2E4 genotypes or both in the non-carriers for the S2 allele (6/7). CONCLUSION/INTERPRETATION: Our results strongly support the hypothesis that severe hyperlipaemia in Type II diabetes crucially depends on genetic factors which impair the clearance of triglyceride-rich lipoproteins.

Oligonucleotide inhibition of the interaction of HIV-1 Tat protein with the trans-activation responsive region (TAR) of HIV RNA.

The interaction of HIV-1 Tat protein with its recognition sequence, the trans-activation responsive region TAR is a potential target for drug discovery against HIV infection. We show by use of an in vitro competition filter binding interference assay that synthetic oligodeoxyribonucleotides complementary to the HIV-1 TAR RNA apical stem-loop and bulge region inhibit the binding of Tat protein or a Tat peptide (residues 37-72) better than two small molecules that have been shown to bind TAR RNA, Hoechst 33258 and neomycin B. The inhibition is not sensitive to length between 13 and 16 residues or precise positioning but shorter oligonucleotides are less effective. Enhanced inhibition was obtained for a 16-mer 2'-O-methyl oligoribonucleotide but not for C5-propyne pyrimidine-substituted oligonucleotides. Control non-antisense oligonucleotides were occasionally also effective in filter binding interference but only the complementary antisense 2'-O-methyl oligoribonucleotide was effective in gel mobility shift assays in direct TAR binding or in interference with Tat peptide binding to the TAR stem-loop. This is the first demonstration of effective inhibition of the Tat-TAR interaction by nuclease-stabilized oligonucleotide analogues.

Influence of the nature of the porphyrin ligand on the nuclease activity of metalloporphyrin-oligonucleotide conjugates designed with cationic, hydrophobic or anionic metalloporphyrins.

The synthesis of metalloporphyrin-oligonucleotide conjugates with different metalloporphyrin moieties are described as well as the comparison of their in vitro nuclease efficiency toward a single-stranded DNA target. Between cationic, anionic and hydrophobic manganese porphyrins covalently linked to the oligonucleotide, the best nuclease activity was obtained with the cationic ones, suggesting that the affinity of the cleaver to the DNA target is a key factor.

Structure/nuclease activity relationships of DNA cleavers based on cationic metalloporphyrin-oligonucleotide conjugates.

The covalent attachment of a managanese-tris(methylpyridiniumyl)porphyrin entity to an antisense oligonucleotide allowed sequence-selective oxidative cleavage of DNA when the metalloporphyrin was activated by potassium monopersulfate (KHSO5). We prepared several structurally modified metallo-porphyrin-oligonucleotide conjugates in order to find out the most efficient compound for in vitro DNA cleavage. The nature and the length of the tether were modulated, the metalloporphyrin entity was modified (metal, ligand), and different ways of activation of the metalloporphyrin were assayed. We noticed that the location of the peptidic bond within the linker could greatly affect the cleavage efficiency of the different conjugates. We showed that the most efficient conjugate for oxidative DNA cleavage was a manganese tetracationic porphyrin-oligonucleotide compound. When the metalloporphyrin moiety was activated by a reducing agent in the presence of molecular oxygen, DNA cleavage was efficient at suitable concentrations of the reducing agent, in order to avoid the reduction of the activated DNA cleaver, a putative high-valent metal-oxo species, by the excess of reducing agent.

Preparation and nuclease activity of hybrid "metallotris(methylpyridinium)porphyrin oligonucleotide" molecules having a 3'-loop for protection against 3'-exonucleases.

A 5'-GCGAAAGC minihairpin structure was added to the 3'-end of an oligonucleotide substituted at the 5'-end by a manganese cationic porphyrin in order to enhance the 3'-exonuclease resistance of these cleaver-antisense molecules. The influence of this minihairpin on the 3'-exonuclease resistance, the binding affinity to a target ssDNA, and the cleaving efficiency of Mn-cationic porphyrin oligonucleotide conjugates was compared to that of the parent molecule without the 3'-hairpin. The results showed that the 3'-hairpin slightly decreased the binding affinity and consequently the cleaving efficiency of the conjugated molecule toward a target sequence, but the much higher nuclease resistance makes 3'-minihairpin-protected metalloporphyrin oligonucleotides good candidates as reactive antisense oligonucleotides for studies on cells.