Clinical Correlates of the PET-based Braak Staging Framework in Alzheimer's Disease.

In vivo Alzheimer's disease diagnosis and staging is traditionally based on clinical features. However, the agreement between clinical and pathological Alzheimer's disease diagnosis, whose diagnosis assessment includes amyloid and Braak histopathological tau staging, is not completely convergent. The development of positron emission tomography (PET) tracers targeting neurofibrillary tangles offers prospects for advancing the staging of Alzheimer's disease from both biological and clinical perspectives. Recent advances in radiochemistry made it possible to apply the postmortem Braak staging framework to tau-PET images obtained in vivo. Here, our aim is to provide a narrative review of the current literature on the relationship between Alzheimer's disease clinical features and the PET-based Braak staging framework. Overall, the available studies support the stepwise increase in disease severity following the advance of PET-based Braak stages, with later stages being associated with worse cognitive and clinical symptoms. In line with this, there is a trend for unimpaired cognition, mild cognitive impairment, and Alzheimer's disease dementia to be compatible with early, intermediate, and late patterns of tau deposition based on PET-based Braak stages. Moreover, neuropsychiatric symptom severity seems to be linked to the extent of tau-PET signal across Braak areas. In sum, this framework seems to correspond well with the clinical progression of Alzheimer's disease, which is an indication of its potential utility in research and clinical practice, especially for detecting preclinical tau levels in individuals without symptoms. However, further research is needed to improve the generalizability of these findings and to better understand the applications of this staging framework.

Neuroinflammation Biomarkers in the AT(N) Framework Across the Alzheimer's Disease Continuum.

In the past years, neuroinflammation has been widely investigated in Alzheimer's disease (AD). Evidence from animal, in vivo and post-mortem studies has shown that inflammatory changes are a common feature of the disease, apparently happening in response to amyloid-beta and tau accumulation. Progress in imaging and fluid biomarkers now allows for identifying surrogate markers of neuroinflammation in living individuals, which may offer unprecedented opportunities to better understand AD pathogenesis and progression. In this context, inflammatory mediators and glial proteins (mainly derived from microglial cells and astrocytes) seem to be the most promising biomarkers. Here, we discuss the biological basis of neuroinflammation in AD, revise the proposed neuroinflammation biomarkers, describe what we have learned from anti-inflammatory drug trials, and critically discuss the potential addition of these biomarkers in the AT(N) framework.

Alopecia areata difusa: uma forma atípica muitas vezes subdiagnosticada / Diffuse alopecia areata: an atypical form often misdiagnosed

Alopecia areata é doença inflamatória auto-imune, de etiologia multifatorial, manifestada em indivíduos geneticamente predispostos, que acomete ofolículo piloso. Pode ser classificada de diversas maneiras, sendo uma delas a forma atípica denominada difusa. Essa forma talvez seja a de mais difícil diagnostico, devido a dificuldade em se diferenciá-la da alopecia androgenética e do eflúvio telógeno. A raridade da apresentação e a dificulade diagnóstica e terapêutica motivaram a demonstração deste caso, que relata presença de rarefação capilardifusa, não cicatricial, iniciada há 3 anos, em paciente masculino, de 16 anos de idade. Foi tratado para alopecia androgenética sem melhora e apenasapós biópsia confirmou-se o diagnostico dessa forma de alopecia areata. Para tal, é necessária exclusão de outras doenças como alopecia androgené-tica, eflúvio telógeno, sífilis e lúpus eritematoso (AU)

Alopecia areata is an autoimmune inflammatory disease of multifactorial aetiology, manifested in genetically predisposed individuals, which affects the hair follicle. It can be classified in several ways, one being called atypical diffuse. This form is perhaps the most difficult to diagnose because of the difficulty in differentiating it from androgenetic alopecia and telogen effluvium. The rarity of presentation and the difficulty of diagnosis and treatment of our patient -a 16 years-old male-, which reports the presence of diffuse thinning hair, no scar that started 3 years ago. He was treated for androgenetic alopecia with no improvement, and just after biopsy the diagnosis of this form of alopecia areata was confirmed. For that, is necessary the exclusion of other diseases such as androgenic alopecia, telogen effluvium, syphilis and lupus erythematosus. trials with long-term results to help patients with this atypical form of alopecia areata (AU)

Bilateral retinochoroiditis caused by an atypical strain of Toxoplasma gondii.

BACKGROUND: A 53-year-old man presented with an acute bilateral posterior uveitis with extensive necrotising retinochoroiditis but without chorioretinal scarring. A thorough workup did not reveal any underlying disease. The possibilities of atypical ocular toxoplasmosis as well as herpetic retinal necrosis were considered and specific therapy instituted, with little improvement. The patient died within 2 months as result of an undifferentiated squamous cell carcinoma. METHODS: Histopathological examination, immunohistochemistry and multilocus polymerase chain reaction confirmed Toxoplasma gondii infection of the retina RESULTS: Macroscopic examination of enucleated globe showed extensive retinal necrosis and vitreous detachment. Histological examination of retinal tissue identified numerous round-to-elliptical toxoplasmic cysts within the retina, with retinal necrosis and minimal choroidal inflammation. Immunohistochemical analyses confirmed that the cysts were due to T gondii. DNA extracted from formalin-fixed, paraffin-embedded tissue sections was subjected to multilocus polymerase chain reaction (PCR) analysis at the following typing loci: SAG1, SAG2, SAG3, SAG4, B1, NTS2, GRA6 and GRA7. DNA sequencing of positive PCR products at the NTS2, SAG1 and GRA7 loci confirmed the presence of a non-archetypal strain of T gondii infecting the eye of the patient experiencing a severe, atypical ocular toxoplasmosis CONCLUSION: A highly divergent, non-archetypal strain of T gondii was responsible for causing a severe, atypical bilateral retinochoroiditis in a patient from Brazil.

Caseinolytic activity of fruit extract from Opuntia ficus-indica on bovine, caprine, and ovine sodium caseinates.

The rates and extents of hydrolysis of alpha(S)- and beta-caseins from bovine, caprine, and ovine sodium caseinates produced by an enzymatic extract of the fruit of Opuntia ficus-indica, (L.) Miller were evaluated and compared with those produced by a commercial animal rennet. A mechanistic model based on a pseudo-first-order enzymatic reaction, in the presence of first-order deactivation of the enzyme, was postulated and successfully fitted to the experimental data. The animal rennet exhibited higher enzymatic efficiency than the fruit extract, irrespective of the source (i.e., bovine, caprine, or ovine) and the type (i.e., alpha(S)- or beta-casein) of substrate. The enzymatic efficiency (k(cat)/K(m)) for alpha(S)-casein ranged from 72 to 220 and from 43 to 65 L g(-1) h(-1), and for beta-casein from 242 to 742 and from 55 to 164 L g(-1) h(-1), for the animal rennet and the enzymatic extract of O. ficus-indica, respectively. Finally, it was observed that beta-casein from caprine and ovine caseinates was degraded by O. ficus-indica faster than its alpha(S) counterpart, but the reverse was observed for bovine caseinate.

[Violence and social inequalities: mortality rates due to homicides and life conditions in Salvador, Brazil]. / Violência e desigualdade social: mortalidade por homicídios e condições de vida em Salvador, Brasil.

INTRODUCTION: Some studies have been questioning the association between poverty and violence. This study's purpose is to assess the distribution of homicide indicators associated with living conditions in Salvador, Brazil. METHODS: A cluster study for the years 1991 to 1994 was carried out including the 75 data centers of the city of Salvador, BA, Brazil. Using death certificates for the study period, yearly mortality rates and mortality ratios were estimated. The 1991 census data of monthly wages and years of education for all family providers were used to define a four-category variable related to living conditions. Mortality rates due to homicide and the relative risk regarding the lowest living condition area were calculated for each social stratum. The 95% confidence intervals were calculated using the Confidence Interval Analysis software. RESULTS: The highest mortality rates due to homicide were seen in the poorest areas. The relative risk due to homicide for the lowest and the highest living condition areas was statistically significant at 5% level and ranged from 2.9 to 5.1. CONCLUSIONS: The data show a strong association between social inequalities and homicide in this urban area, emphasizing the importance of crime reduction programs.

The microstructure and distribution of micro-organisms within mature Serra cheese.

The distribution of micro-organisms in mature Serra, a traditional Portuguese cheese made from unpasteurised ewes' milk without added starter culture, was examined by light microscopy and electron microscopy. Four populations of micro-organisms were recognized according to their position within the cheese: (i) those present as apparently axenic colonies within the curd matrix; (ii) bacteria growing along curd junctions; (iii) yeasts and bacteria present in the smear on the surface of the cheese and (iv) bacteria found in cracks which penetrated the outer part of the cheese from the rind. Two types of crystals were observed, together with contaminants of vegetable origin and somatic cells originating from the milk.