Neuropsychological and genetic differences between age-associated memory impairment and mild cognitive impairment entities

OBJECTIVE: To neuropsychologically and genetically compare age-associated memory impairment (AAMI) and mild cognitive impairment (MCI) entities and to determine what proportion of AAMI diagnosed individuals could also receive a MCI diagnosis. To compare the distribution of a previously known genetic risk factor for Alzheimer's disease (apolipoprotein E common polymorphism) associated with these two conditions with a sample of the normal aging. DESIGN: Neuropsychological and genetic assessments in AAMI and MCI individuals. Genetic assessment in AAMI, MCI, and control subjects. SETTING: General health centers and geriatric homes from northeastern Spain (Catalunya). PARTICIPANTS: One hundred and four subjects presenting subjective memory complaints were selected and the AAMI and MCI criteria were applied. One hundred and twenty-four healthy Spanish subjects age 50 and older were defined as controls. MEASUREMENTS: Memory, language, and frontal lobe functions were assessed using standard neuropsychological tests. The apolipoprotein E (apo E) polymorphism was obtained by using polymerase chain reaction (PCR) and HhaI restriction endonuclease. RESULTS: Sixty-seven percent of previously diagnosed AAMI individuals could also be identified as MCI subjects. These MCI cases differed from those only-AAMI individuals both in neuropsychological and genetic analyses, performing worse not only on memory but also on language and frontal lobe tests and presenting high and low prevalences of the apo E epsilon 3/epsilon 4 and epsilon 3/epsilon 3 genotypes, respectively. The general AAMI sample of 93 individuals also differed from controls in the apo E genotype and allele distributions but these differences were no longer present after subtracting the MCI cases (63 subjects). These findings reflect that the differences between the memory impaired sample and the control sample regarding the apo E polymorphism were mainly attributable to MCI individuals and not to those who received only a diagnosis of AAMI alone. CONCLUSIONS: Our findings suggest that among AAMI subjects, those who also fulfill the MCI criteria present a neuropsychological and genetic profile closer to that previously related to Alzheimer's disease than those individuals only eligible for a diagnosis of AAMI. However, our findings also suggest that using only the AAMI criteria still appears to select a population that differs genetically from the normal older population.     

Birth seasons and heights among girls and boys below 12 years of age: lasting effects and catch-up growth among native Amazonians in Bolivia

Background: Seasons affect many social, economic, and biological outcomes, particularly in low-resource settings, and some studies suggest that birth season affects child growth.

Aim: To study a predictor of stunting that has received limited attention: birth season.

Subjects and methods: This study uses cross-sectional data collected during 2008 in a low-resource society of horticulturists-foragers in the Bolivian Amazon, Tsimane’. It estimates the associations between birth months and height-for-age Z-scores (HAZ) for 562 girls and 546 boys separately, from birth until age 11?years or pre-puberty, which in this society occurs ～13–14?years.

Results: Children born during the rainy season (February–May) were shorter, while children born during the end of the dry season and the start of the rainy season (August–November) were taller, both compared with their age–sex peers born during the rest of the year. The correlations of birth season with HAZ were stronger for boys than for girls. Controlling for birth season, there is some evidence of eventual partial catch-up growth, with the HAZ of girls or boys worsening until?～?age 4–5?years, but improving thereafter. By age 6?years, many girls and boys had ceased to be stunted, irrespective of birth season.

Conclusion: The results suggest that redressing stunting will require attention to conditions in utero, infancy and late childhood.     

Glioblastoma and malignant melanoma: Serendipitous or anticipated association?

We describe a patient who had primary glioblastoma (GB) and malignant melanoma (MM). A 78‐year‐old man presented with several weeks to months of history of gait disturbance, confusion, memory disturbance, and worsening speech. Imaging studies performed on admission revealed a large frontotemporal lobe mass associated with the surrounding zone of vasogenic edema. Given the patient's medical history of incomplete biopsy of a midback tumor performed three weeks before, the presumptive clinical diagnosis was metastatic MM. Pathological examination of frozen sections of fragmented specimens obtained at stereotactic biopsy performed on admission revealed a high‐grade malignant neoplasm characterized by discohesive cells in a blue myxoid background and abundant foci of tumor necrosis. Given these features, in conjunction with the abovementioned pathological report, the frozen section diagnosis by the neuropathologist was “neoplasm identified, favor melanoma.” Due to the paucity of lesional tissue, a limited immunohistochemistry performed on the permanent sections revealed positive staining of lesional cells for Sox10 alone using a multiplex MART1/Sox10 immunostain and S‐100 protein, an immunohistochemical profile supporting the presumptive frozen section diagnosis. A tumor debulk procedure, performed two weeks later, revealed histopathologic features most compatible with GB, IDH wild‐type. Thus, additional immunohistochemistry on the permanent sections revealed positive staining of glial fibrillary acidic protein (GFAP), Sox10, and S‐100 protein as well as negative staining of gp100, a complex carbohydrate matrix protein in embryonic melanosomes, using a specific antibody HMB45. The concomitant occurrence of MM and GB in our patient underscores the association between these two entities. Our literature review suggests that the sporadic co‐occurrence of these two conditions is likely not serendipitous.     

SARS-CoV-2 infection after alemtuzumab in a multiple sclerosis patient: milder disease symptoms in comparison with coinfected relatives: a case report and review of the literature

Neurological Sciences - Literature data reporting SARS-CoV-2 infection in multiple sclerosis (MS) patients recently treated with immunodepleting agents as cladribine and alemtuzumab are very...     

Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.     

The influence of small field output factors simulated uncertainties on the calculated dose in VMAT plans for brain metastases: a multicentre study

Objectives:This multicentric study was carried out to investigate the impact of small field output factors (OFs) inaccuracies on the calculated dose in volumetric arctherapy (VMAT) radiosurgery brain plans.Methods:Nine centres, realised the same five VMAT plans with common planning rules and their specific clinical equipment Linac/treatment planning system commissioned with their OFs measured values (OFbaseline). In order to simulate OFs errors, two new OFs sets were generated for each centre by changing only the OFs values of the smallest field sizes (from 3.2 × 3.2 cm² to 1 × 1 cm²) with well-defined amounts (positive and negative). Consequently, two virtual machines for each centre were recommissioned using the new OFs and the percentage dose differences ΔD (%) between the baseline plans and the same plans recalculated using the incremented (OFup) and decremented (OFdown) values were evaluated. The ΔD (%) were analysed in terms of planning target volume (PTV) coverage and organs at risk (OARs) sparing at selected dose/volume points.Results:The plans recalculated with OFdown sets resulted in higher variation of doses than baseline within 1.6 and 3.4% to PTVs and OARs respectively; while the plans with OFup sets resulted in lower variation within 1.3% to both PTVs and OARs. Our analysis highlights that OFs variations affect calculated dose depending on the algorithm and on the delivery mode (field jaw/MLC‐defined). The Monte Carlo (MC) algorithm resulted significantly more sensitive to OFs variations than all of the other algorithms.Conclusion:The aim of our study was to evaluate how small fields OFs inaccuracies can affect the dose calculation in VMAT brain radiosurgery treatments plans. It was observed that simulated OFs errors, return dosimetric calculation accuracies within the 3% between concurrent plans analysed in terms of percentage dose differences at selected dose/volume points of the PTV coverage and OARs sparing.Advances in knowledge:First multicentre study involving different Planning/Linacs about undetectable errors in commissioning output factor for small fields.     

Accreditation of processes in hepatology

The Spanish Association for the Study of the Liver decided in 2006 to develop a project to assess the quality of the professionals, processes and medical units dealing with the management of patients with liver diseases in Spain. The current article reports the criteria proposed to assess the quality and the accreditation of the processes in hepatology. The processes considered include most patients with liver diseases and the accreditation system designed is highly specific. This document, together with a previous one published in gastroenterología y hepatología concerning the accreditation of the professionals and a third document dealing with the accreditation of liver units that will be published soon, form the basis of the quality assessment of hepatology in our country.     

Manganese superoxide dismutase activity and incidence of hepatocellular carcinoma in patients with Child-Pugh class A liver cirrhosis: a 7-year follow-up study.

AIMS: To evaluate possible modifications in the manganese superoxide dismutase (MnSOD) activity during neoplastic transformation of a cirrhotic liver and to find out whether its assessment may have predictive value to identify cirrhotic patients at a higher risk of hepatocellular carcinoma (HCC). METHODS: Seventy-one consecutive subjects with Child-Pugh class A liver cirrhosis were recruited. At the time of enrolment, HCC was diagnosed in 20 cirrhotic patients. The 51 cirrhotic patients without HCC were followed up for the occurrence of tumour by 6-monthly screening for 7 years. During follow-up, 16 patients developed HCC. Seventy healthy subjects formed the control group. MnSOD activity was assayed spectrophotometrically. RESULTS: Serum MnSOD activity was significantly lower in 70 healthy subjects compared with 51 cirrhotic patients and 20 cirrhotic patients with HCC. Cirrhotic patients who developed HCC during follow-up showed significantly higher values of MnSOD activity than HCC-free patients. The best cut-off of MnSOD activity was 0.40 U/ml. At this cut-off, chi2 analysis revealed that MnSOD activity was significantly different between the HCC-free cirrhotic patients and cirrhotic patients who developed HCC. CONCLUSION: The present findings suggest that during neoplastic transformation of cirrhotic liver, an increase in MnSOD activity may occur already during the precancerous phase, making this enzyme a probable malignancy-associated parameter.