Primary Tuberculosis of the Esophagus

Os autores reportam o caso de uma doente de 38 anos de idade com um quadro clínico de odinofagia, dor retroesternal e emagrecimento. Os exames complementares de diagnóstico revelaram a presença de uma lesão ulcerada no esófago, como forma de manifestação de tuberculose primária do esófago. A Tuberculose esofágica é uma doença pouco frequente, sendo responsável por 0,15% da mortalidade por tuberculose. A Tuberculose primária do esófago, sem envolvimento de outros órgãos, como o nosso caso clínico, é ainda mais raro. A maioria dos casos é tratada de forma eficaz com tuberculostáticos, sendo que o atraso no diagnóstico e início da terapêutica dita um mau prognóstico

An anaphase surveillance mechanism prevents micronuclei formation from frequent chromosome segregation errors

Micronuclei are a hallmark of cancer and several other human disorders. Recently, micronuclei were implicated in chromothripsis, a series of massive genomic rearrangements that may drive tumor evolution and progression. Here, we show that Aurora B kinase mediates a surveillance mechanism that integrates error correction during anaphase with spatial control of nuclear envelope reassembly to prevent micronuclei formation. Using high-resolution live-cell imaging of human cancer and non-cancer cells, we uncover that anaphase lagging chromosomes are more frequent than previously anticipated, yet they rarely form micronuclei. Micronuclei formation from anaphase lagging chromosomes is prevented by a midzone-based Aurora B phosphorylation gradient that stabilizes kinetochore-microtubule attachments and assists spindle forces required for anaphase error correction while delaying nuclear envelope reassembly on lagging chromosomes, independently of microtubule density. We propose that a midzone-based Aurora B phosphorylation gradient actively monitors and corrects frequent chromosome segregation errors to prevent micronuclei formation during human cell division.We thank António Pereira and Ana Almeida for assistance with CH-STED, Ariana Jacome for the generation of lentiviral vectors, Cristina Ferrás and Marco Novais-Cruz for drawing attention to the effects of nocodazole treatment and washout on the Aurora B phosphorylation gradient, current and former lab members for suggestions, and Jonathan Higgins and Andrew McAinsh for discussing results prior to publication. This work was funded by the European Research Council (ERC) consolidator grant CODECHECK , under the European Union’s Horizon 2020 research and innovation programme (grant agreement 681443 ), and Fundação para a Ciência e a Tecnologia of Portugal ( PTDC/MED-ONC/3479/2020 )

The Montreal Cognitive Assessment (MoCA) as a screening test for cognitive dysfunction in multiple sclerosis

This study investigates the utility of the Portuguese version of Montreal Cognitive Assessment (MoCA) as a screening-method for identifying cognitive dysfunction (CD) in multiple sclerosis (MS). The 118 participants with comprehensive neuropsychological assessment were divided into two subgroups: (I) MS group (n = 59) and (II) control group (n = 59). The MS patients were classified as cognitively intact (n = 26) or impaired (n = 33, 56%). The results indicated that the MoCA is a psychometrically valid instrument in assessment of MS patients. The Multiple Linear Regression analyses highlighted the significant influence of Modified Fatigue Impact Scale and Irregular Word Reading Test on MoCA performance. The MoCA total score showed a good discriminative capacity between cognitively impaired and cognitively intact subjects. In addition, there were significant differences in MoCA cognitive domain scores between groups. The MoCA total score cut-off point for identifying CD in MS patients was a score below 26 points (AUC = 0.837, CI = 0.736-0.937). A proposed EM-MoCA-Subscore for identifying the MS-related cognitive impairment (max. score = 19 points, cut-off <17 points, AUC = 0.871, CI = 0.784-0.958), can reduce administration time for cognitive screening in clinical settings. The MoCA is a useful and sensitive instrument to identify the MS-related cognitive impairment.info:eu-repo/semantics/publishedVersio

Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children

Background: We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H2O2) play a role in the putative association. Methods: Cross-sectional evaluation of 305 children aged 8–9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H2O2 by a microplate fluorometric assay. Results: U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H2O2 decreased with P-AGT. Conclusions: A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin–angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H2O2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.This project was supported by funds from Fundo Europeu de Desenvolvimento Regional (FEDER) from Programa Operacional Factores de Competitividade – COMPETE (FCOMP-01-0124-FEDER-028751), by national funds from the Portuguese Foundation for Science and Technology (FCT) (PTDC/DTP-PIC/0239/2012) and by Calouste Gulbenkian Foundation, that granted the study design and data collection and analysis. Liane Correia-Costa was supported by FCT (grant SFRH/SINTD/95898/2013), Teresa Sousa was supported by FCT and POPH/FSE (EC) (Ciência 2008 and SFRH/BPD/112005) and Franz Schaefer was supported by the ERA-EDTA Research Programme and the KfH Foundation for Preventive Medicine. The Epidemiology Research Unit (EPIUnit) is funded by FCT (UID/DTP/04750/2013)

Association of myeloperoxidase levels with cardiometabolic factors and renal function in prepubertal children

INTRODUCTION: Myeloperoxidase (MPO), an enzyme linking obesity and cardiovascular (CV) risk in adults, has rarely been studied in young children and no studies assessed its association with renal function. We sought to explore a possible association between serum MPO levels, obesity, CV risk factors and renal function in prepubertal children. MATERIALS/METHODS: Cross-sectional evaluation of 309 children aged 8-9 years (161 normal weight, 148 overweight/obese), members of the birth cohort Generation I (Portugal). Anthropometrics (body mass index (BMI), waist-to-height ratio (WHtR) and % body fat mass (%BFM) by bioelectrical impedance analysis), 24-h ambulatory blood pressure monitoring and pulse wave velocity (PWV) were measured. Insulin resistance was estimated by the HOMA index (considering serum fasting glucose and insulin determinations). Serum MPO levels were assessed by immunoenzymatic assay. RESULTS: MPO levels were positively associated with obesity indices (BMI z-score, WHtR and %BFM). Higher MPO levels were associated with higher 24-h and night-time mean arterial pressure, with nondipping and with higher values of insulin resistance. In normal weight children, the endothelial function, as evaluated indirectly by PWV, was an independent predictor of MPO levels. In overweight/obese children, estimated glomerular filtration rate increased significantly across tertiles of MPO (Ptrend = 0·031) and this association held after adjustment for age, sex, neutrophil and monocyte counts and CV risk factors. CONCLUSIONS: Our results reinforce the role of MPO as a risk marker in obesity and related CV morbidities in young children. MPO levels associate with the dipping pattern and PWV and, among overweight/obese children, an association exists between MPO and renal function

Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania

Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria, such as sub-Saharan Africa. However, their long-term usefulness in these high transmission areas remains unclear. It has been suggested that documentation of the S769N PfATPase6 mutations may indicate an emergence of artemisinin resistance of Plasmodium falciparum in the field. The present study assessed PfATPase6 mutations (S769N and A623E) in 615 asymptomatic P. falciparum infections in Tanzania but no mutant genotype was detected. This observation suggests that resistance to artemisinin has not yet been selected in Tanzania, supporting the Ministry of Health's decision to adopt artemether+lumefantrine as first-line malaria treatment. The findings recommend further studies to assess PfATPase6 mutations in sentinel sites and verify their usefulness in monitoring emergency of ACT resistance

HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis

Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14. Of relevance, HIPK2-defective cells do not phosphorylate H2B and do not successfully complete cytokinesis leading to accumulation of binucleated cells, chromosomal instability, and increased tumorigenicity. However, how HIPK2 and H2B are recruited to the midbody during cytokinesis is still unknown. Here, we show that regardless of their direct (H2B) and indirect (HIPK2) binding of chromosomal DNA, both H2B and HIPK2 localize at the midbody independently of nucleic acids. Instead, by using mitotic kinase-specific inhibitors in a spatio-temporal regulated manner, we found that Aurora-B kinase activity is required to recruit both HIPK2 and H2B to the midbody. Molecular characterization showed that Aurora-B directly binds and phosphorylates H2B at Ser32 while indirectly recruits HIPK2 through the central spindle components MgcRacGAP and PRC1. Thus, among different cytokinetic functions, Aurora-B separately recruits HIPK2 and H2B to the midbody and these activities contribute to faithful cytokinesis

The optical/NIR afterglow of GRB 111209A: Complex yet not unprecedented

Context. Afterglows of gamma-ray bursts (GRBs) are simple in the most basic model, but can show many complex features. The ultra-long duration GRB 111209A, one of the longest GRBs ever detected, also has the best-monitored afterglow in this rare class of GRBs. Aims. We want to address the question whether GRB 111209A was a special event beyond its extreme duration alone, and whether it is a classical GRB or another kind of high-energy transient. The afterglow may yield significant clues. Methods. We present afterglow photometry obtained in seven bands with the GROND imager as well as in further seven bands with the Ultraviolet/Optical Telescope (UVOT) on-board the Neil Gehrels Swift Observatory. The light curve is analysed by multi-band modelling and joint fitting with power-laws and broken power-laws, and we use the contemporaneous GROND data to study the evolution of the spectral energy distribution. We compare the optical afterglow to a large ensemble we have analysed in earlier works, and especially to that of another ultra-long event, GRB 130925A. We furthermore undertake a photometric study of the host galaxy. Results. We find a strong, chromatic rebrightening event at ≈0.8 days after the GRB, during which the spectral slope becomes redder. After this, the light curve decays achromatically, with evidence for a break at about 9 days after the trigger. The afterglow luminosity is found to not be exceptional. We find that a double-jet model is able to explain the chromatic rebrightening. The afterglow features have been detected in other events and are not unique. Conclusions. The duration aside, the GRB prompt emission and afterglow parameters of GRB 111209A are in agreement with the known distributions for these parameters. While the central engine of this event may differ from that of classical GRBs, there are multiple lines of evidence pointing to GRB 111209A resulting from the core-collapse of a massive star with a stripped envelope