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.

Identifying canonical and replicable multi-scale intrinsic connectivity networks in 100k+ resting-state fMRI datasets.

Despite the known benefits of data-driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter-subject correspondence limits the clinical utility of rsfMRI and its application to single-subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates via the use of multi-model-order independent component analysis (ICA). We also study the feasibility of estimating subject-specific ICNs via spatially constrained ICA. The results show that the subject-level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large-scale ICNs require less data to achieve specific levels of (within- and between-subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject-level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within-subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.

Sex dimorphism of weight and length at birth: evidence based on disorders of sex development.

BACKGROUND: Males have higher weight and length at birth than females. AIM: To verify the influence of the Y chromosome and the action of intrauterine androgens on weight and length at birth of children with Disorders of Sex Development (DSD). SUBJECTS AND METHODS: A cross-sectional and retrospective study. Patients with Turner syndrome (TS), complete (XX and XY), mixed (45,X/46,XY) and partial (XY) gonadal dysgenesis (GD), complete (CAIS) and partial (PAIS) androgen insensitivity syndromes and XX and XY congenital adrenal hyperplasia (CAH) were included. Weight and length at birth were evaluated. RESULTS: Weight and length at birth were lower in TS and mixed GD when compared to XY and XX DSD cases. In turn, patients with increased androgen action (117 cases) had higher weight and length at birth when compared to those with absent (108 cases) and decreased (68 cases) production/action. In birthweight, there was a negative influence of the 45,X/46,XY karyotype and a positive influence of increased androgen and gestational age. In birth length, there was a negative influence of the 45,X and 45,X/46,XY karyotypes and also a positive influence of increased androgen and gestational age. CONCLUSIONS: The sex dimorphism of weight and length at birth could possibly be influenced by intrauterine androgenic action.

Living in endemic area for infectious diseases accelerates epigenetic age.

Inflammaging is a low-grade inflammatory state generated by the aging process that can contribute to frailty and age-related diseases in the elderly. However, it can have distinct effects in the elderly living in endemic areas for infectious diseases. An increased inflammatory response may confer protection against infectious agents in these areas, although this advantage can cause accelerating epigenetic aging. In this study, we evaluated the inflammatory profile and the epigenetic age of infected and noninfected individuals from an endemic area in Brazil. The profile of cytokines, chemokines and growth factors analyzed in the sera of the two groups of individuals showed similarities, although infected individuals had a higher concentration of these mediators. A significant increase in IL-1ra, CXCL8, CCL2, CCL3 and CCL4 production was associated with leprosy infection. Notably, elderly individuals displayed distinct immune responses associated with their infection status when compared to adults suggesting an adaptive remodelling of their immune responses. Epigenetic analysis also showed that there was no difference in epigenetic age between the two groups of individuals. However, individuals from the endemic area had a significant accelerated aging when compared to individuals from São Paulo, a non-endemic area in Brazil. Moreover, the latter cohort was also epigenetically aged in relation to an Italian cohort. Our data shows that living in endemic areas for chronic infectious diseases results in remodelling of inflammaging and acceleration of epigenetic aging in individuals regardless of their infectious status. It also highlights that geographical, genetic and environmental factors influence aging and immunosenescence in their pace and profile.

The impact of mentoring in trauma and orthopaedic training: a systematic review.

INTRODUCTION: Trauma and orthopaedics is renowned for being a challenging yet rewarding career. The value of mentorship in medical and surgical training is known to be beneficial; however, the prevalence and quality of mentorship opportunities in orthopaedics are less well studied. Identifying the strengths and weaknesses of mentoring programmes in orthopaedic training and recognising barriers to effective mentorship are key to unlocking the full potential of future orthopaedic surgeons. METHODS: A comprehensive search of PubMed, Medline, EMBASE and the Cochrane Library was performed. All studies published in the English language that reported data on mentorship programmes in orthopaedic training were included. FINDINGS: A total of 23 studies met the inclusion criteria. These studies demonstrated that formal mentorship programmes in orthopaedics are lacking but are sought after, with a positive influence on satisfaction and future career choice/subspecialty selection identified. Several barriers to mentoring in the field were recognised including the difficulty faced by female trainees, the availability of mentors and time constraints. The opportunity to choose a mentor, a mentor with the same interests, regular meetings and the option of gender congruent mentorship were all identified as crucial requirements for effective mentorship. CONCLUSION: Mentorship opportunities must be more accessible to all orthopaedic trainees alike and should aim to incorporate the attributes identified to provide the highest calibre of training to prospective orthopaedic surgeons.

Boat noise impacts early life stages in the Lusitanian toadfish: A field experiment.

Marine traffic is the most common and chronic source of ocean noise pollution. Despite the evidence of detrimental effects of noise exposure on fish, knowledge about the effects on the critical early life stages - embryos and larvae - is still scarce. Here, we take a natural habitat-based approach to examine potential impacts of boat noise exposure in early life stages in a wild fish population of the Lusitanian toadfish (Halobatrachus didactylus). In-situ experiments were carried out in the Tagus estuary, an estuary with significant commercial and recreational boat traffic. Nests with eggs were exposed to either ambient (control) or boat noise (treatment), for 1 fortnight. Eggs were photographed before being assigned to each treatment, and after exposure, to count number of eggs and/or larvae to assess survival, and sampled to study development and oxidative stress and energy metabolism-related biomarkers. Data concerns 4 sampling periods (fortnights) from 2 years. Results indicate that offspring survival did not differ between treatments, but boat noise induced a detrimental effect on embryos and larvae stress response, and on larvae development. Embryos showed reduced levels of electron transport system (ETS), an energy metabolism-related biomarker, while larvae showed higher overall stress responses, with increased levels of superoxide dismutase (SOD) and DNA damage (oxidative stress related responses), ETS, and reduced growth. With this study, we provided the first evidence of detrimental effects of boat noise exposure on fish development in the field and on stress biomarker responses. If these critical early stages are not able to compensate and/or acclimate to the noise stress later in the ontogeny, then anthropogenic noise has the potential to severely affect this and likely other marine fishes, with further consequences for populations resilience and dynamics.

The gut microbiota profile in psoriasis: a Brazilian case-control study.

The pathogenesis of psoriasis, an immune-mediated chronic inflammatory skin disease, remains unclear. Studies have shown an association between psoriasis and intestinal inflammation; in this context, the influence of the gut microbiota on the immune response of psoriasis has become a focus of recent research. The present research evaluated the composition and diversity of the gut microbiota of 21 participants with psoriasis from a Brazilian referral dermatology service compared to 24 healthy controls. A stool sample was collected from each participant at the time of inclusion in the study, and the samples were analysed by sequencing the 16S rRNA gene. The recruitment of research participants involved matching between groups by sex, age, body mass index, comorbidities and smoking and the exclusion of several criteria that could potentially influence the gut microbiota and the interpretation of the data. There was an increase in the Dialister genus and Prevotella copri species in patients with psoriasis compared to the control group. A reduction in the Ruminococcus, Lachnospira and Blautia genera, as well as in the Akkermansia muciniphila species, was also verified in the psoriasis group compared to the control group. Furthermore, patients with psoriasis exhibited less gut microbiota diversity than controls.

Corneal haze post photorefractive keratectomy.

Corneal haze represents subepithelial corneal fibrosis, a manifestation of a pathological healing process. It occurs as a result of an epithelial-stromal lesion involving a break in the epithelial barrier. It is an inflammatory response that involves the migration, multiplication and differentiation of keratocytes into mature myofibroblasts, causing loss of corneal transparency. Although it is a transient phenomenon, this complication is feared following refractive photokeratectomy (PRK), because it can cause alterations in the quality of vision, refractive regression and decreased visual acuity. The severity of these symptoms is correlated with the severity of the corneal haze, which can be assessed clinically or by objective means such as corneal densitometry measurement. The frequency and severity of corneal haze increase with the depth of photoablation in PRK and are therefore increased during the treatment of severe ametropia. Considering that no consensus exists, the application of mitomycin C (MMC) intraoperatively and topical corticosteroids postoperatively are conventionally used to inhibit collagen synthesis, sometimes in combination with various protocols depending on the center or surgeon. This review of the literature reports the current knowledge on corneal haze, in order to better understand it and optimise its prevention in the context of a decreased MMC supply, which has occurred in the past and could recur in the future.

Tetanus vaccination in pregnant women: a systematic review and meta-analysis of the global literature.

OBJECTIVES: This study aimed to determine the effect of several factors on the uptake of tetanus vaccination in pregnant women. STUDY DESIGN: This is a systematic review and meta-analysis of the global literature. METHODS: The search strategy was carried out in the EMBASE and MEDLINE (Pubmed) databases, without language restrictions. The databases were searched from the beginning until May 2020. Fixed and random effect models were applied according to the methodological heterogeneity between the included studies. The I2 test was performed to assess the magnitude of the heterogeneity. The results were presented as a grouped odds ratio (OR) with a 95% confidence interval (CI) and a significance level of 0.05. RESULTS: The initial search strategy generated 14,349 original articles. In total, 31 studies met all inclusion criteria and 20 articles were included in the meta-analysis. The grouped and subgroup analyses showed a significant association between tetanus vaccination and the following factors: higher number of prenatal visits (OR: 2.00; 95% CI: 1.17-3.42), higher maternal age (OR: 1.24, 95% CI: 1.02-1.50), being single (OR: 1.41; 95% CI: 1.20-1.65), professional vaccine guidance (OR: 9.00; 95% CI: 1.81-44.75) and uptake of influenza vaccine (OR: 5.87; 95% CI: 1.39-24.73). CONCLUSIONS: The uptake of tetanus vaccine in pregnant women is associated with various factors. The identification of these factors is an important step towards the implementation of public health strategies aimed at improving immunisation against tetanus in pregnant women.

Sodium palatability in male spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHRs) ingest more NaCl than normotensive strains. Here we investigated NaCl intake and taste reactivity in adult male SHRs and normotensive Holtzman rats treated or not with AT1 receptor antagonist centrally in euhydrated condition and after fluid depletion. Taste reactivity was measured by the number of orofacial expressions to intra-oral infusions of 0.3 M NaCl. In euhydrated condition, intra-oral infusions of 0.3 M NaCl produced greater number of hedonic responses in SHRs than in normotensive rats, without differences in the number of aversive responses. Compared to euhydrated condition, the treatment with the diuretic furosemide + low dose of captopril (angiotensin converting enzyme blocker) increased the number of hedonic and reduced the number of aversive responses to intra-oral NaCl in normotensive rats, without changing the number of hedonic or aversive responses in SHRs. Losartan (AT1 receptor antagonist, 100 ng/1 µl) injected intracerebroventricularly in SHRs abolished 0.3 M NaCl intake induced by water deprivation + partial rehydration, whereas only transiently (first 30 min of the 60 min test) reduced hedonic responses, without changes in aversive responses to intra-oral NaCl. Losartan intracerebroventricularly also only transiently (first 30 min) reduced the number of hedonic responses to intra-oral NaCl in euhydrated SHRs. The results suggest that NaCl palatability is increased and independent from body fluid balance in SHRs. The results also suggest that central AT1 receptors are part of the mechanisms activated to increase NaCl intake and palatability in SHRs. A partial dissociation between NaCl intake and palatability in SHRs is also suggested.

Eyelid Chemical Burns: A Multidisciplinary And Challenging Approach.

During second- and third-degree eyelid sulfuric acid burns, many surgeons prefer to wait until primary wound separation occurs before grafting. However, this approach may miss the chance to recover the eyelids and can cause ectropion, resulting in delayed eyeball healing with exposure keratitis. We propose that early eyelid release and grafting makes a significant difference in long-term outcomes and improves eyeball healing. Here, we present the case of a woman who presented second- and third-degree burns of the eyelids secondary to physical domestic assault with acid, who had an early surgical management with a full-thickness skin graft. Ten days after surgery, we found that the graft had survived totally, and the donor site of the right arm had already healed. Eyelids were successfully grafted and the functions of both eyelids were well recovered, allowing complete cover of the eyeball. Two months after surgery, functional and cosmetic results were satisfying, with no postoperative lagophthalmos or difficulties with exposure-related problems. Case reports of eyelid chemical burns are very few. No specific and codified management of eyelid chemical burns was found in the literature search. This case report demonstrated that a multidisciplinary approach led by both ophthalmologists and plastic surgeons must be decided early (<6h) in order to achieve synergistic and coordinated management between the eye and the eyelid. There is a significant improvement in ocular healing with early excision and grafting of eyelids after sulfuric acid burn.

En cas de brûlure du 2ème ou du 3ème degré des paupières par acide sulfurique, de nombreux chirurgiens préfèrent attendre la séparation spontanée de l'escarre avant de greffer. Cette stratégie comporte le risque d'une cicatrisation défectueuse source d'ectropion, d'occlusion incomplète et de kératite. Nous conjecturons qu'une excision-greffe précoce améliore le pronostic à long terme de ce type de brûlure. Nous présentons le cas d'une femme victime d'une agression intra-familiale à l'acide sulfurique, souffrant de brûlure des 2ème et 3ème degrés des paupières traitée par excision-greffe de peau totale précoce. À J10, la greffe était totalement intégrée et le site donneur (bras droit) était cicatrisé. La fonction palpébrale était normale et l'occlusion oculaire complète. Ces bons résultats persistaient à 2 mois, sans lagophtalmie ni défaut d'occlusion, avec un aspect esthétique correct. Les rapports de brûlures chimiques des paupières sont peu fréquents et il nous n'avons pas trouvé de protocole dans la littérature. Ce cas clinique illustre la nécessité d'une analyse précoce (dans les 6h) par ophtalmologiste et plasticien afin de définir une stratégie coordonnée vis à vis du globe oculaire et de la paupière. L'excision-greffe précoce améliore la pronostic oculaire après brûlure par acide sulfurique.

Zinc, manganese, and copper amino acid complexes improve performance and bone characteristics of layer-type chicks under thermoneutral and cold stress conditions.

Two experiments were designed to evaluate the effect of mineral-amino acid complexes (AACM) as a partial replacement of inorganic mineral (IM) in layer-type chicks' diets. Both studies had the same dietary treatments, where in experiment 1 (Exp. 1) was conducted under thermoneutral conditions from 0 to 35 D and chicks in experiment 2 (Exp. 2) were exposed to cold stress conditions at nighttime during the first 15 D and to thermoneutral condition from 16 to 35 D. For each trial, 1,200 one-day-old Lohmann Brown chicks were used, with 20 cage replicates with 30 chicks per cage. Treatments consisted of the control diet (IM; with 70, 70, and 8 mg/kg of zinc [Zn], manganese [Mn], and copper [Cu], respectively) and the treatment diet (AACM, with 40, 40, and 2.75 mg/kg of Zn, Mn, and Cu, respectively, from IM sources, along with 30, 30, and 5.25 mg/kg of Zn, Mn, and Cu, respectively). Data were submitted to analysis of variance, and means were compared using the t-test (P < 0.05). In Exp. 1, there were no significant differences between treatments on chick performance. However, AACM-fed chicks had higher thymus (P = 0.03) and cecum weight (P < 0.01), superior micromineral deposition in the tibias (P < 0.01), and reduced phosphorus excretion (P = 0.03). In Exp. 2, chicks fed with AACM had higher body weight gain (P = 0.04), better average daily feed intake (P = 0.03), lower phosphorus excretion (P = 0.02), and higher liver and pancreas weight (P < 0.01) in the last week of the study. In conclusion, chicks fed with AACM under thermoneutral conditions had higher bone mineralization and reduced excretion of phosphorus, and in adverse conditions, AACM improves performance and liver and pancreas weight, also reducing phosphorus excretion.

Effect of Saccharomyces cerevisiae UFMG A-905 in a murine model of food allergy.

Food allergy is triggered when there is an abnormal activation of the immune system by food allergens. Currently, there is no curative therapy for this pathological condition. Due to the immunomodulatory properties of probiotics they are potential candidates as therapeutic tools for food allergy. Therefore, the aim of this study was to evaluate the probiotic effect of Saccharomyces cerevisiae UFMG A-905 (905) in an in vivo model of food allergy. Probiotic effect was assessed by clinical, histological, immunological and microbiological parameters analysis. Furthermore, we also evaluated if 905 after inactivation has an effect, as well as if such an effect is dose dependent. Our results showed that oral administration of only viable 905 promotes a significant attenuation of tissue injury and myeloperoxidase (MPO) activity levels. Moreover, the treatment reduced interleukin 17 levels, and administration of the supernatant from the yeast culture also promoted a significant decrease in MPO levels. However, considering the systemic parameters, immunoglobulin (Ig)E and IgG anti-ovalbumin, which are essentials for triggering the allergic process, there was no effect, suggesting that the yeast promotes a local but not a systemic effect in the model evaluated. In addition, we found that only high doses of viable 905 were able to attenuate the signs of inflammation. In conclusion, oral administration of 905 led to a local effect that depends on the viability of the yeast.