POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project

Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients’ literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.     

A Comparison of Liver Disease Mortality With HIV and Overdose Mortality Among Georgia Prisoners and Releasees: A 2-Decade Cohort Study of Prisoners Incarcerated in 1991

Objectives. We investigated whether eventual causes of death among a cohort of inmates imprisoned in the southeastern United States differed from those in previous prisoner studies.Methods. We matched 23 510 prisoners in Georgia, a state with historically low levels of heroin consumption but moderate amounts of injection drug use, who were incarcerated on June 30, 1991, to death registries through 2010. Main exposure was 4-year time intervals over 2 decades of observation; main outcome was mortality from liver disease, HIV, and overdose.Results. Although the HIV-related mortality rate exceeded that from liver-related conditions before 2003, liver disease subsequently surpassed HIV as a cause of death. Among 3863 deaths, 22 (0.6%) occurred within 2 weeks after release from prison. Of these, only 2 were caused by accidental poisoning (likely drug overdose). Cardiovascular disease and cancer were the most frequent causes of death in this aging cohort.Conclusions. Our study design deemphasized immediate deaths but highlighted long-term sequelae of exposure to viral hepatitis and alcohol. Treating hepatitis C and implementing interventions to manage alcohol use disorders may improve survival among prisoners in the Southeast.Drug use, incarceration, and mortality are intertwined: the use of illicit drugs can result in both incarceration and premature death. A 2010 international meta-analysis of prisoners'' survival after their release into the community emphasized mortality from overdose in the 2 weeks following discharge, possibly attributable to loss of opiate tolerance after forced sobriety in prison,1 but a more recent publication illustrates how this pattern may vary among subpopulations.2Long-term consequences of injection drug use include hepatitis C and HIV infection. In the United States, sexual exposure is the most common mode of HIV transmission, but the hepatitis C epidemic is mainly driven by the injection of drugs, even if the drug use is not sustained.3 HIV prevalence is 3 times as common among prisoners as among the general population,4 but hepatitis C prevalence is 13 times as high.5,6 Sequelae that could lead to death from hepatitis C typically occur 2 to 4 decades after injection drug use was initiated. Little is known about the long-term survival of inmates, particularly in the southeastern United States, where historical and recent patterns of drug use may differ from those in other regions.In contrast with other studies that have examined cohorts of released inmates, we sought to assess long-term prisoner survival by retrospectively following a cohort composed of a cross section of all imprisoned persons in the state of Georgia on a single day in 1991. In a previous study, we did not observe significantly higher mortality among members of this cohort immediately after release from prison than in the subsequent postrelease period.7 Multiple sources suggest that heroin use is less common in Georgia than in other states. Between 2002 and 2012, consistently fewer than 6.5% of men jailed in Atlanta, the capital of and largest city in Georgia, had evidence of heroin in their urine samples.8,9 The prevalence of opiate use in Atlanta was among the lowest for any city studied in the past decade by the Office of the National Drug Control Policy.8–10 In particular, heroin use was lower than in Washington State, site of a previous study of former inmate mortality.11 According to the Treatment Episode Data Set–Admissions for 1992 to 2010 from the Substance Abuse and Mental Health Services Administration, heroin addiction accounted for only 1.6% of admissions for drug rehabilitation in Georgia, but 9.7% in Washington State and 14.2% nationally.12In assessment of risk for hepatitis C, needle use—whether for heroin, cocaine, or another drug—is more important than what is injected. Needle use in Georgia is not uncommon. According to population-wide National Survey on Drug Use and Health data for 2002 to 2009, 1.1% of Georgians have ever used a needle to inject drugs, including cocaine—a moderate rate compared with the frequency in Washington State, where lifetime prevalence is 2.7%, and nationally, where prevalence is 1.6%.13 State-level data on needle use prior to 2002 are not publically available from the Substance Abuse and Mental Health Services Administration.The prevalence of hepatitis C in the Georgia general population is moderately high, especially in Atlanta. At Grady Memorial Hospital, the safety net charity hospital for Atlanta, the prevalence of hepatitis C among ambulatory primary care patients is 7%. A liver clinic established at this hospital saw 807 unique patients in its first 5 years of existence and was still receiving 60 new patient referrals each month through 2010.14 Three quarters of the patients were African American, and most patients were born between 1945 and 1965; 64% were former drug users, and only 4% were currently using.14 High prevalence of hepatitis C in this baby boomer birth cohort probably reflects time-limited parenteral drug use decades ago, perhaps as early as the Vietnam war era.15 Despite relatively low levels of heroin use in the state, we hypothesized that the prevalence of hepatitis C would be high among inmates in the Georgia prison system who were born between 1945 and 1965.We sought to describe the leading causes of death over 2 decades in a large cohort of all Georgians who were in state prisons on June 30, 1991, and to evaluate whether the immediate mortality following prison discharge was low, because Georgia is a state with low heroin use. In light of the moderate background rates of injection drug use in Georgia, we hypothesized that mortality from liver-related causes would rise over time as the cohort aged. Our first aim was to rank the causes of death and categorize which deaths occurred in prison, immediately after release, and subsequently. Second, we compared deaths from liver disease to those from HIV in 4-year intervals between 1991 and 2010.     

Comparison of two dietary assessment methods by food consumption: results of the German National Nutrition Survey II

Purpose

To further characterise the performance of the diet history method and the 24-h recalls method, both in an updated version, a comparison was conducted.

Methods

The National Nutrition Survey II, representative for Germany, assessed food consumption with both methods. The comparison was conducted in a sample of 9,968 participants aged 14–80. Besides calculating mean differences, statistical agreement measurements encompass Spearman and intraclass correlation coefficients, ranking participants in quartiles and the Bland–Altman method.

Results

Mean consumption of 12 out of 18 food groups was higher assessed with the diet history method. Three of these 12 food groups had a medium to large effect size (e.g. raw vegetables) and seven showed at least a small strength while there was basically no difference for coffee/tea or ice cream. Intraclass correlations were strong only for beverages (>0.50) and revealed the least correlation for vegetables (<0.20). Quartile classification of participants exhibited more than two-thirds being ranked in the same or adjacent quartile assessed by both methods. For every food group, Bland–Altman plots showed that the agreement of both methods weakened with increasing consumption.

Conclusions

The cognitive effort essential for the diet history method to remember consumption of the past 4 weeks may be a source of inaccurateness, especially for inhomogeneous food groups. Additionally, social desirability gains significance. There is no assessment method without errors and attention to specific food groups is a critical issue with every method. Altogether, the 24-h recalls method applied in the presented study, offers advantages approximating food consumption as compared to the diet history method.

     

Neuronal activity regulated pentraxin (narp) and GluA4 subunit of AMPA receptor may be targets for fluoxetine modulation

Fluoxetine is the foremost prescribed antidepressant. Drugs acting on monoaminergic system may also regulate glutamatergic system. Indeed, the investigation of proteins associated with this system, such as Narp (neuronal activity-dependent pentraxin) and GluA4 subunit of AMPA receptor may reveal poorly explored modulations triggered by conventional antidepressants. This study aimed to uncover neurochemical mechanisms underlying the chronic fluoxetine treatment, mainly by evaluating these protein targets in the prefrontal cortex and in the hippocampus. Mice received a daily administration of fluoxetine (0.1, 1 or 10 mg/kg, p.o.) or potable water (vehicle group) for 21 days. These animals were submitted to the forced swim test (FST) to verify antidepressant-like responses and the open-field test (OFT) to assess locomotor activity. Modulation of signaling proteins was analyzed by western blot. Chronic treatment with fluoxetine (1 and 10 mg/kg) was effective, since it reduced the immobility time in the FST, without altering locomotor activity. Fluoxetine 10 mg/kg increased CREB phosphorylation and BDNF expression in the prefrontal cortex and hippocampus. Noteworthy, in the hippocampus fluoxetine also promoted Akt activation and augmented Narp expression. In the prefrontal cortex, a significant decrease in the expression of the GluA4 subunit and Narp were observed following fluoxetine administration (10 mg/kg). The results provide evidence of novel molecular targets potentially involved in the antidepressant effects of fluoxetine, since in mature rodents Narp and GluA4 are mainly expressed in the GABAergic parvalbumin-positive (PV+) interneurons. This may bring new insights into the molecular elements involved in the mechanisms underlying the antidepressant effects of fluoxetine.

     

Sodium-channel defects in benign familial neonatal-infantile seizures

Ion-channel gene defects are associated with a range of paroxysmal disorders, including several monogenic epilepsy syndromes. Two autosomal dominant disorders present in the first year of life: benign familial neonatal seizures, which is associated with potassium-channel gene defects; and benign familial infantile seizures, for which no genes have been identified. Here, we describe a clinically intermediate variant, benign familial neonatal-infantile seizures, with mutations in the sodium-channel subunit gene SCN2A. This clinico-molecular correlation defines a new benign familial epilepsy syndrome beginning in early infancy, an age at which seizure disorders frequently have a sombre prognosis.     

A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection

BACKGROUND: We previously demonstrated that short-cycle structured intermittent therapy (SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum levels of lipids. Adherence to such a regimen may be problematic for certain patients. METHODS: Eight patients with a history of receiving combination ART that maintained suppression of plasma HIV RNA to <50 copies/mL received a once-daily SIT regimen of didanosine, lamivudine, and efavirenz. RESULTS: For 7 patients, suppression of plasma HIV RNA to <50 copies/mL was maintained for 60-84 weeks. Four patients with adequate samples had no evidence for an increase in plasma viremia for up to 72 weeks, by use of an assay with a limit of detection of <1 copy/mL. The lack of rebound viremia may be the result of the persistence of efavirenz in plasma on day 7 of the no-therapy period, as was detected in 7 of 7 patients. There was no significant change in CD4(+) T cell counts or serum hepatic transaminase or lipid levels. CONCLUSION: A once-daily short-cycle SIT regimen maintained suppression of plasma HIV RNA while preserving CD4(+) T cell counts. Such a regimen may have importance in resource-limited settings where the monetary cost of continuous ART is prohibitive.     

FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability

Chromosome 1q41‐q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41‐q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41‐q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described. Seizures are a prominent feature of 1q41‐q42 deletion syndrome; therefore, we hypothesized that pathogenic FBXO28 variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41‐q42 deletion syndrome and WDR26 encephalopathy. We distinguish FBXO28 encephalopathy from both of these disorders with more severe intellectual impairment, drug‐resistant epilepsy, and hyperkinetic movement disorders.     

Prophylactic Insulin Treatment of Diabetes-prone BB/OK Rats by Application of a Sustained Release Insulin Implant

Normoglycemic diabetes-prone BB/OK rats aged 33, 45 or 75 days were subjected to prophylactic insulin treatment by means of a single subcutaneous application of a sustained release insulin implant. The single application of a sustained release insulin implant decreased the incidence of diabetes or delayed the onset of the disease in BB/OK rats of all treatment groups. Prophylactic insulin administration caused a transient hypoglycemic period accompanied by an inhibition of glucose stimulated insulin secretion and a decrease of the insulin content of Langerhans' islets as detectable in vitro . Compared to islets of normoglycemic controls pancreatic islets isolated from hypoglycemic BB/OK rats within 7-21 days after the insulin application at 45 days of age displayed a decreased susceptibility of the cells to complement-dependent cytotoxicity of the monoclonal islet cell surface antibody (ICSA) K14D10 but not to the cytotoxic effect of the ICSA M3aG8. The appearance of complement-dependent antibody-mediated cytotoxicity to islet cells and pancreatic exocrine cells in serum regarded as a sign of immune dysregulation in BB/OK rats seems not to be affected by insulin prophylaxis and was detectable during hypoglycemia as well as in the subsequent normoglycemic state. In conclusion, BB/OK rats of different age can be protected from diabetes by a single application of a sustained release insulin implant. Insulin and/or hypoglycemia seem to influence the expression of cell surface antigens, thus render the islets of Langerhans less vulnerable to immune cytolysis, whereas the appearance of humoral immunological abnormalites is not affected.