La sclerosi tuberosa

La sclerosi Tuberosa o Tuberous Sclerosis Complex (TSC) \ue8 una sindrome autosomica dominante caratterizzata anche da un precoce coinvolgimento della cute. Data la marcata variabilit\ue0 clinica della TSC, \ue8 possibile osservare quadri paucisintomatici in cui \ue8 evidenziabile solo qualche lesione ipomelanotica. Le chiazze ipomelanotiche sono di grande importanza nella diagnosi di TSC. Sono considerate uno dei segni maggiori quando in numero maggiore di 4 , ma non sempre facili da differenziare da altre chiazze presenti dai primi mesi di vita come i nevi acromici, la vitiligine, l'ipomelanosi di Ito, le macchie ipocromiche del soggetto sano. Partendo dalla evidenza che nelle chiazze ipomelanotiche di TSC viene prodotta una ridotta quantit\ue0 di sudore rispetto alla cute sana, un test all'amido-iodio \ue8 stato utilizzato su chiazze ipomelanotiche in alcuni soggetti affetti da TSC. La comparsa di pigmentazione molto pi\uf9 intensa allo sbocco delle ghiandole sudorali nelle chiazze ipomelanotiche rispetto alla cute sana, permette di suggerire questo semplice metodo per la conferma diagnostica di chiazze ipomelanotiche TSC. La possibilit\ue0 di poter eseguire indagini di biologia molecolare su diverse lesioni cutanee in soggetto affetti da TSC ha consentito l'identificazione di vie metaboliche alternative responsabili dello stimolo iperproliferativo alla base dello sviluppo anche delle lesioni cutanee

Angioedema delle labbra

L\u2019angioedema non sempre \ue8 sinonimo di allergia. Esistono, infatti, delle peculiari entit\ue0 cliniche a patogenesi non-istamino mediata quali l\u2019angioedema ereditario, l\u2019angioedema acquisito e l\u2019angioedema indotto da farmaci ACE inibitori, che pongono al clinico notevoli difficolt\ue0 diagnostiche. Negli ultimi anni si \ue8 assistito ad un significativo avanzamento delle conoscenze riguardo ai meccanismi molecolari alla base di queste forme che ha permesso, tra l\u2019altro, di chiarire l\u2019importante ruolo patogenetico ricoperto dalle chinine, in particolare dalla bradichinina, consentendo di identificare potenziali target per l\u2019azione di nuovi farmaci. La conoscenza delle basi patogenetiche, degli aspetti clinici e delle peculiari alterazioni biochimiche di queste forme di angioedema \ue8 di fondamentale importanza per un corretto inquadramento diagnostico e trattamento terapeutico

skin necrosis caused by flunitrazepam abuse

n/

Calculating Colimits Compositionally

We show how finite limits and colimits can be calculated compositionally using the algebras of spans and cospans, and give as an application a proof of the Kleene Theorem on regular languages

Metabolomic profiling to dissect the role of visceral fat in cardiometabolic health

OBJECTIVE: Abdominal obesity is associated with increased risk of type 2 diabetes (T2D) and cardiovascular disease. The aim of this study was to assess whether metabolomic markers of T2D and blood pressure (BP) act on these traits via visceral fat (VF) mass. METHODS: Metabolomic profiling of 280 fasting plasma metabolites was conducted on 2,401 women from TwinsUK. The overlap was assessed between published metabolites associated with T2D, insulin resistance, or BP and those that were identified to be associated with VF (after adjustment for covariates) measured by dual‐energy X‐ray absorptiometry. RESULTS: In addition to glucose, six metabolites were strongly associated with both VF mass and T2D: lactate and branched‐chain amino acids, all of them related to metabolism and the tricarboxylic acid cycle; on average, 38.5% of their association with insulin resistance was mediated by their association with VF mass. Five metabolites were associated with BP and VF mass including the inflammation‐associated peptide HWESASXX, the steroid hormone androstenedione, lactate, and palmitate. On average, 29% of their effect on BP was mediated by their association with VF mass. CONCLUSIONS: Little overlap was found between the metabolites associated with BP and those associated with insulin resistance via VF mass

Geo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app

Understanding the geographical distribution of COVID-19 through the general population is key to the provision of adequate healthcare services. Using self-reported data from 1 960 242 unique users in Great Britain (GB) of the COVID-19 Symptom Study app, we estimated that, concurrent to the GB government sanctioning lockdown, COVID-19 was distributed across GB, with evidence of ’urban hotspots’. We found a geo-social gradient associated with predicted disease prevalence suggesting urban areas and areas of higher deprivation are most affected. Our results demonstrate use of self-reported symptoms data to provide focus on geographical areas with identified risk factors

Geo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app

Understanding the geographical distribution of COVID-19 through the general population is key to the provision of adequate healthcare services. Using self-reported data from 1 960 242 unique users in Great Britain (GB) of the COVID-19 Symptom Study app, we estimated that, concurrent to the GB government sanctioning lockdown, COVID-19 was distributed across GB, with evidence of ’urban hotspots’. We found a geo-social gradient associated with predicted disease prevalence suggesting urban areas and areas of higher deprivation are most affected. Our results demonstrate use of self-reported symptoms data to provide focus on geographical areas with identified risk factors

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling

BACKGROUND/OBJECTIVES: Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence VF development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM. SUBJECTS/METHODS: In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the ‘VFM diet score’ in the remainder of the sample. Using linear regression (adjusted for covariates, including BMI and total fat mass) we investigated associations between the VFM diet score, the blood metabolomics profile and the faecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (greater than or equal to1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence. RESULTS: Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (Beta[s.e.]: 0.281[0.091]; P=0.002), butyrylcarnitine (0.199[0.087]; P=0.023) and hippurate (−0.297[0.095]; P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042[0.011], P=8.47 × 10−5), VFM (0.057[0.019], P=2.73 × 10−3) and hippurate (−0.075[0.032], P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016[0.004], P=9.82 × 10−6). CONCLUSION: We linked a dietary VFM score and VFM to Eubacterium dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM