Focal neuronal lipofuscinosis (FNL) is an uncommon epileptic disorder related to an excess of lipofuscin accumulation within dysmorphic-appearing neurons (DANs), whose epileptogenic mechanisms are ...still poorly understood. It shares some clinical and neuroimaging similarities with focal cortical dysplasia of type IIb (FCDIIb), but it represents a different pathological entity. Here, we identified two patients with FNL among a 10-year cohort of 323 patients who underwent neurosurgery for a focal pharmacoresistant epilepsy. We describe the electroclinical, metabolic and neuropathological features of both patients with FNL who benefited from a comprehensive presurgical investigation. While the previous reports showed frontal lobe localization of the lesion, FNL was identified in the temporal lobe, in one of our patients. EEG investigations in both patients showed striking focal and rich interictal activity resembling that described in FCDIIb. Besides focal intraneuronal lipofuscin accumulation, the neuropathological analysis demonstrated that somata of DANs were surrounded by a large amount of GABAergic presynaptic buttons, suggesting the involvement of interneurons in the epileptogenicity of FNL. To further explore the role of GABAergic transmission in the generation of epileptiform activity in FNL, we performed in vitro multi-electrode array recordings on the post-surgery tissue from one patient. Spontaneous interictal-like discharges (IILDs) were identified only in the restricted area displaying the highest density of lipofuscin-containing DANs, suggesting a close correlation between the density of lipofuscin-containing neurons and epileptogenicity. Moreover, IILDs were blocked by the GABAA receptor antagonist gabazine. All together, these findings showed how GABA signaling may contribute to the generation of interictal-like activity in FNL tissue.
Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome.
To estimate the age-specific cumulative risks of developing various tumors using a ...large series of families with mutations of the MLH1, MSH2, and MSH6 genes.
Families with Lynch syndrome enrolled between January 1, 2006, and December 31, 2009, from 40 French cancer genetics clinics participating in the ERISCAM (Estimation des Risques de Cancer chez les porteurs de mutation des gènes MMR) study; 537 families with segregating mutated genes (248 with MLH1; 256 with MSH2; and 33 with MSH6) were analyzed.
Age-specific cumulative cancer risks estimated using the genotype restricted likelihood (GRL) method accounting for ascertainment bias.
Significant differences in estimated cumulative cancer risk were found between the 3 mutated genes (P = .01). The estimated cumulative risks of colorectal cancer by age 70 years were 41% (95% confidence intervals CI, 25%-70%) for MLH1 mutation carriers, 48% (95% CI, 30%-77%) for MSH2, and 12% (95% CI, 8%-22%) for MSH6. For endometrial cancer, corresponding risks were 54% (95% CI, 20%-80%), 21% (95% CI, 8%-77%), and 16% (95% CI, 8%-32%). For ovarian cancer, they were 20% (95% CI, 1%-65%), 24% (95% CI, 3%-52%), and 1% (95% CI, 0%-3%). The estimated cumulative risks by age 40 years did not exceed 2% (95% CI, 0%-7%) for endometrial cancer nor 1% (95% CI, 0%-3%) for ovarian cancer, irrespective of the gene. The estimated lifetime risks for other tumor types did not exceed 3% with any of the gene mutations.
MSH6 mutations are associated with markedly lower cancer risks than MLH1 or MSH2 mutations. Lifetime ovarian and endometrial cancer risks associated with MLH1 or MSH2 mutations were high but do not increase appreciably until after the age of 40 years.
The pancreatic islet blood flow of rats 24 h after a prolonged
(48-h) glucose infusion was investigated using a nonradioactive
microsphere technique. In the basal state, islet blood flow was
...significantly increased in previously hyperglycemic rats (HG) compared
to that in controls (C). During an iv glucose challenge, both plasma
insulin and islet blood flow were increased in the two groups, but
these increases were significantly higher in HG than in C rats.
Although less pronounced, the results were similar when glucose was
injected into the carotid artery toward the brain at a dose that did
not modify the peripheral glucose level. The effect of this
intracarotid injection was abolished after bilateral subdiaphragmatic
vagotomy in both C and HG rats. Furthermore, in the latter group, both
plasma insulin concentration and islet blood flow returned to values
similar to those observed in the basal state in C rats. After
pretreatment with the α2-adrenoceptor agonist clonidine,
the insulin response to the intracarotid glucose load was totally
blunted in the two groups of rats. By contrast, whereas such a
pretreatment lowered the glucose-induced increase in islet blood flow
in C rats, it was without effect in HG rats. These data suggest that a
period of hyperglycemia and/or hyperinsulinemia is sufficient to induce
a perturbation of pancreatic islet blood flow, which appears to be
mainly due to an increased parasympathetic activity, whereas the
decrease in sympathetic tone does not play a role. These modifications
in autonomic nervous system activity could be due to alterations in
some brain areas involved in “glucose sensing.”
Chemical approach of synthetic immunogens from human renin Galen, F X; Evin, G; Carelli, C ...
International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology,
1987, Letnik:
14, Številka:
4
Journal Article
Background
Little is known about risk factors for mortality in older patients with COVID‐19 and neuropsychiatric conditions.
Methods
We conducted a multicentric retrospective observational study at ...Assistance Publique‐Hôpitaux de Paris. We selected inpatients aged 70 years or older, with COVID‐19 and preexisting neuropsychiatric comorbidities and/or new neuropsychiatric manifestations. We examined demographics, comorbidities, functional status, and presentation including neuropsychiatric symptoms and disorders, as well as paraclinical data. Cox survival analysis was conducted to determine risk factors for mortality at 40 days after the first symptoms of COVID‐19.
Results
Out of 191 patients included (median age 80 interquartile range 74–87), 135 (71%) had neuropsychiatric comorbidities including cognitive impairment (39%), cerebrovascular disease (22%), Parkinsonism (6%), and brain tumors (6%). A total of 152 (79%) patients presented new‐onset neuropsychiatric manifestations including sensory symptoms (6%), motor deficit (11%), behavioral (18%) and cognitive (23%) disturbances, gait impairment (11%), and impaired consciousness (18%). The mortality rate at 40 days was 19.4%. A history of brain tumor or Parkinsonism or the occurrence of impaired consciousness were neurological factors associated with a higher risk of mortality. A lower Activities of Daily Living score (hazard ratio HR 0.69, 95% confidence interval CI 0.58–0.82), a neutrophil‐to‐lymphocyte ratio ≥ 9.9 (HR 5.69, 95% CI 2.69–12.0), and thrombocytopenia (HR 5.70, 95% CI 2.75–11.8) independently increased the risk of mortality (all p < .001).
Conclusion
Understanding mortality risk factors in older inpatients with COVID‐19 and neuropsychiatric conditions may be helpful to neurologists and geriatricians who manage these patients in clinical practice.
Ce travail porte sur la modélisation de la lixiviation du béton en tenant compte des effets dus aux granulats. Le modèle consiste à dériver les équations microscopiques pour trouver les paramètres de ...transport à l'échelle macroscopique en se basant sur une approche de développement asymptotique. Cette approche permet de définir un comportement à échelle macroscopique avec un tenseur de diffusion effectif tenant compte de l'effet de tortuosité. Ces paramètres dépendent de la morphologie et du domaine occupé par la phase granulaire dans le volume dans lequel la diffusion se déroule. L'utilisation de cette méthode dans un code éléments finis permet alors de déterminer la tortuosité due à la présence des granulats et la diffusivité du milieu équivalent. Enfin, une comparaison entre résultats expérimentaux et modélisation est présentée.
The extent to which microbiota alterations define or influence the outcome of metabolic diseases is still unclear, but the byproducts of microbiota metabolism are known to have an important role in ...mediating the host-microbiota interaction. Here, we identify that in both pre-clinical and clinical settings, metabolic syndrome is associated with the reduced capacity of the microbiota to metabolize tryptophan into derivatives that are able to activate the aryl hydrocarbon receptor. This alteration is not merely an effect of the disease as supplementation with AhR agonist or a Lactobacillus strain, with a high AhR ligand-production capacity, leads to improvement of both dietary- and genetic-induced metabolic impairments, particularly glucose dysmetabolism and liver steatosis, through improvement of intestinal barrier function and secretion of the incretin hormone GLP-1. These results highlight the role of gut microbiota-derived metabolites as a biomarker and as a basis for novel preventative or therapeutic interventions for metabolic disorders.
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•Production of AhR agonists by the gut microbiota is reduced in metabolic syndrome•Restoring AhR signaling induces beneficial effects on metabolic syndrome•Restoration of the gut barrier defect and secretion of GLP-1 are involved
Natividad et al. show that metabolic syndrome is associated with an impaired capacity of the gut microbiota to metabolize tryptophan into aryl hydrocarbon receptor (AhR) agonists in mice and humans. Supplementation with AhR agonist or a Lactobacillus strain naturally producing AhR ligands improves both dietary- and genetic-induced metabolic impairments.
Introduction
The prevalence of mental health disorders among people who use drugs is high and well documented. This hard‐to‐reach population faces a very low awareness and access to mental health ...care, especially in developing countries. The objectives of this study were to design and assess a quick screening tool (QST) that community‐based organisations (CBO) could routinely apply to a Vietnamese population of people who inject drugs (PWID), in order to refer them appropriately to mental health specialists.
Methods
We devised a tool that included nine questions covering anxiety, depression, suicide risk and psychotic symptomatology. Its use required no specific background and 2 h training. Specificity and sensitivity of the QST were assessed in a population of 418 PWID recruited via respondent driven sampling, using the Mini International Neuropsychiatric Interview questionnaire plus clinical evaluation as a reference standard. Acceptability was assessed using a self‐administered anonymous questionnaire submitted to all CBO members who used the QST.
Results
CBO members considered the QST easy to use, relevant and helpful to deal with mental health issues. Area under the curve for detection of any symptom using the QST was 0.770. The maximum sensitivity and specificity were reached with a cut‐off of 2 sensitivity was 71.1% (95% confidence interval 62.4, 78.8), specificity was 75.9% (70.5, 80.7).
Discussion and Conclusions
The QST appeared to be both efficient and well accepted. Given the burden of mental health problems among hard‐to‐reach PWID in developing countries, community‐based screenings such as this one could be a particularly appropriate response.
Animals from the Booroola line of Australian Merino sheep are characterized by a high ovulation rate that can be attributed to the presence of a codominant allele (FecB). The specific function of the ...gene has not been identified. Effective use of the trait within the sheep breeding industry requires one or more genetic markers that can distinguish between alternative alleles at the locus Fec. With a combination of DNA minisatellite markers and polymorphic protein markers, a cluster of seven minisatellite fragments has been identified as being linked to the Fec gene and to the ovine A blood group locus. The minisatellite fragments have been derived from multilocus probes and hence cannot be used to define the chromosomal location of the Fec gene or to serve as diagnostic markers for Fec. The derivation of cloned single locus markers from the minisatellite fragments will enable finer scale mapping of the Fec and the A blood group locus in sheep.