Investigating the porphyrias through analysis of biochemical pathways.

ABSTRACT The porphyrias are a diverse group of metabolic disorders arising from diminished activity of enzymes in the heme biosynthetic pathway. They can present with acute neurovisceral symptoms, cutaneous symptoms, or both. The complexity of these disorders is demonstrated by the fact that some acute porphyria patients with the underlying genetic defect(s) are latent and asymptomatic while others present with severe symptoms. This indicates that there is at least one other risk factor required in addition to the genetic defect for symptom manifestation. A systematic review of the heme biosynthetic pathway highlighted the involvement of a number of micronutrient cofactors. An exhaustive review of the medical literature uncovered numerous reports of micronutrient deficiencies in the porphyrias as well as successful case reports of treatments with micronutrients. Many micronutrient deficiencies present with symptoms similar to those in porphyria, in particular vitamin B6. It is hypothesized that a vitamin B6 deficiency and related micronutrient deficiencies may play a major role in the pathogenesis of the acute porphyrias. In order to further investigate the porphyrias, a computational model of the heme biosynthetic pathway was developed based on kinetic parameters derived from a careful analysis of the literature. This model demonstrated aspects of normal heme biosynthesis and illustrated some of the disordered biochemistry of acute intermittent porphyria (AIP). The testing of this model highlighted the modifications necessary to develop a more comprehensive model with the potential to investigated hypotheses of the disordered biochemistry of the porphyrias as well as the discovery of new methods of treatment and symptom control. It is concluded that vitamin B6 deficiency might be the risk factor necessary in conjunction with the genetic defect to trigger porphyria symptoms

Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation

Background: Trends over time and possible socio-spatial inequalities in the incidence and care of type 1 diabetes mellitus (T1D) in children and adolescents are important parameters for the planning of target-specific treatment structures. Methodology: The incidence and prevalence of type 1 diabetes, diabetic ketoacidosis and severe hypoglycaemia as well as the HbA1c value are presented for under 18-year-olds based on data from the nationwide Diabetes Prospective Follow-up Registry (DPV) and the diabetes registry of North Rhine-Westphalia. Indicators were mapped by sex over time between 2014 and 2020, and stratified by sex, age and regional socioeconomic deprivation for 2020. Results: In 2020, the incidence was 29.2 per 100,000 person-years and the prevalence was 235.5 per 100,000 persons, with the figures being higher in boys than in girls in either case. The median HbA1c value was 7.5%. Ketoacidosis manifested in 3.4% of treated children and adolescents, significantly more often in regions with very high (4.5%) deprivation than in regions with very low deprivation (2.4%). The proportion of severe hypoglycaemia cases was 3.0%. Between 2014 and 2020, the incidence, prevalence and HbA1c levels changed little, while the proportions of ketoacidosis and severe hypoglycaemia decreased. Conclusions: The decrease in acute complications indicates that type 1 diabetes care has improved. Similar to previous studies, the results suggest an inequality in care by regional socioeconomic situation

Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation

Background: Trends over time and possible socio-spatial inequalities in the incidence and care of type 1 diabetes mellitus (T1D) in children and adolescents are important parameters for the planning of target-specific treatment structures. Methodology: The incidence and prevalence of type 1 diabetes, diabetic ketoacidosis and severe hypoglycaemia as well as the HbA1c value are presented for under 18-year-olds based on data from the nationwide Diabetes Prospective Follow-up Registry (DPV) and the diabetes registry of North Rhine-Westphalia. Indicators were mapped by sex over time between 2014 and 2020, and stratified by sex, age and regional socioeconomic deprivation for 2020. Results: In 2020, the incidence was 29.2 per 100,000 person-years and the prevalence was 235.5 per 100,000 persons, with the figures being higher in boys than in girls in either case. The median HbA1c value was 7.5%. Ketoacidosis manifested in 3.4% of treated children and adolescents, significantly more often in regions with very high (4.5%) deprivation than in regions with very low deprivation (2.4%). The proportion of severe hypoglycaemia cases was 3.0%. Between 2014 and 2020, the incidence, prevalence and HbA1c levels changed little, while the proportions of ketoacidosis and severe hypoglycaemia decreased. Conclusions: The decrease in acute complications indicates that type 1 diabetes care has improved. Similar to previous studies, the results suggest an inequality in care by regional socioeconomic situation

Ten Years After: An ‘Austerity Audit’ of Services and Living Conditions for People Living with HIV in the UK, a Decade after the Financial Crisis

Cite as: HIV Psychosocial Network (2018). Ten Years After: An ‘Austerity Audit’ of Services and Living Conditions for People Living with HIV in the UK, a Decade after the Financial Crisis

Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke.

Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730

Inzidenz, Prävalenz und Versorgung von Typ-1-Diabetes bei Kindern und Jugendlichen in Deutschland: Zeittrends und sozialräumliche Lage

Hintergrund: Zeitliche Trends und mögliche sozialräumliche Ungleichheiten hinsichtlich der Häufigkeit und Versorgung von Typ-1-Diabetes mellitus (T1D) bei Kindern und Jugendlichen sind für die Planung von zielgerechten Behandlungsstrukturen von Bedeutung. Methode: Mit Daten der bundesweiten Diabetes-Patienten-Verlaufsdokumentation (DPV) und des Diabetesregisters in Nordrhein-Westfalen wurden für unter 18-Jährige Inzidenz und Prävalenz des Typ-1-Diabetes sowie HbA1c-Wert, diabetische Ketoazidosen und schwere Hypoglykämien dargestellt. Die Indikatoren wurden im Verlauf zwischen 2014 und 2020 nach Geschlecht und für 2020 stratifiziert nach Geschlecht, Alter und regionaler sozioökonomischer Deprivation abgebildet. Ergebnisse: 2020 betrug die Inzidenz 29,2 pro 100.000 Personenjahre und die Prävalenz 235,5 pro 100.000 Personen, mit jeweils höheren Werten bei Jungen als bei Mädchen. Der HbA1c-Wert betrug im Median 7,5 %. Bei 3,4 % der Behandelten trat eine Ketoazidose auf, signifikant häufiger in Regionen mit sehr hoher (4,5 %) als in Regionen mit sehr niedriger Deprivation (2,4 %). Der Anteil schwerer Hypoglykämien lag bei 3,0 %. Zwischen 2014 und 2020 änderten sich Inzidenz, Prävalenz und HbA1c-Wert kaum, während die Anteile von Ketoazidosen und schweren Hypoglykämien abnahmen. Schlussfolgerungen: Die Abnahme von Akutkomplikationen weist auf eine verbesserte Versorgung des Typ-1-Diabetes hin. Ähnlich wie in früheren Studien deuten die Ergebnisse eine Ungleichheit in der Versorgung nach sozialräumlicher Lage an

Physics at a 100 TeV pp collider: Higgs and EW symmetry breaking studies

This report summarises the physics opportunities for the study of Higgs bosons and the dynamics of electroweak symmetry breaking at the 100 TeV pp collider.Comment: 187 pages, 94 figures. Chapter 2 of the "Physics at the FCC-hh" Repor

Inzidenz, Prävalenz und Versorgung von Typ-1-Diabetes bei Kindern und Jugendlichen in Deutschland: Zeittrends und sozialräumliche Lage

Hintergrund: Zeitliche Trends und mögliche sozialräumliche Ungleichheiten hinsichtlich der Häufigkeit und Versorgung von Typ-1-Diabetes mellitus (T1D) bei Kindern und Jugendlichen sind für die Planung von zielgerechten Behandlungsstrukturen von Bedeutung. Methode: Mit Daten der bundesweiten Diabetes-Patienten-Verlaufsdokumentation (DPV) und des Diabetesregisters in Nordrhein-Westfalen wurden für unter 18-Jährige Inzidenz und Prävalenz des Typ-1-Diabetes sowie HbA1c-Wert, diabetische Ketoazidosen und schwere Hypoglykämien dargestellt. Die Indikatoren wurden im Verlauf zwischen 2014 und 2020 nach Geschlecht und für 2020 stratifiziert nach Geschlecht, Alter und regionaler sozioökonomischer Deprivation abgebildet. Ergebnisse: 2020 betrug die Inzidenz 29,2 pro 100.000 Personenjahre und die Prävalenz 235,5 pro 100.000 Personen, mit jeweils höheren Werten bei Jungen als bei Mädchen. Der HbA1c-Wert betrug im Median 7,5 %. Bei 3,4 % der Behandelten trat eine Ketoazidose auf, signifikant häufiger in Regionen mit sehr hoher (4,5 %) als in Regionen mit sehr niedriger Deprivation (2,4 %). Der Anteil schwerer Hypoglykämien lag bei 3,0 %. Zwischen 2014 und 2020 änderten sich Inzidenz, Prävalenz und HbA1c-Wert kaum, während die Anteile von Ketoazidosen und schweren Hypoglykämien abnahmen. Schlussfolgerungen: Die Abnahme von Akutkomplikationen weist auf eine verbesserte Versorgung des Typ-1-Diabetes hin. Ähnlich wie in früheren Studien deuten die Ergebnisse eine Ungleichheit in der Versorgung nach sozialräumlicher Lage an