In cerebral palsy (CP), spasticity is the dominant symptom and hip pain is one of the most common secondary conditions. Aetiology is not clear. Musculoskeletal ultrasound (MSUS) is a low-cost, ...non-invasive imaging technique that allows assessment of structural status, dynamic imaging, and quick contralateral comparison.
A retrospective case-matched-control study. To investigate associated factors with painful spastic hip and to compare ultrasound findings (focusing on muscle thickness) in children with CP vs. typically developing (TD) peers.
Paediatric Rehabilitation Hospital in Mexico City, from August to November 2018.
21 children (13 male, 7 + 4.26 years) with CP, in Gross Motor Function Classification System (GMFCS) levels IV to V, with spastic hip diagnosis (cases) and 21 children age- and sex-matched (7 + 4.28 years) TD peers (controls).
Sociodemographic data, CP topography, degree of spasticity, mobility arch, contractures, Visual Analog Scale (VAS), GMFCS, measurements of the volumes of eight major muscles of the hip joint and MSUS findings of both hips.
All children with CP group reported chronic hip pain. Associated factors for hip pain (high VAS hip pain score) were degree of hip displacement (percentage of migration), Ashworth Level, GMFCS level V. No synovitis, bursitis or tendinopathy was found. Significant differences (p < 0.05) were found in muscle volumes in all hip muscles (right and left) except in the right and left adductor longus.
Though possibly the most important issue with diminished muscle growth in CP children is the influence on their long-term function, it is likely that training routines that build muscle size may also increase muscle strength and improve function in this population. To improve the choice of treatments in this group and maintain muscle mass, longitudinal investigations of the natural history of muscular deficits in CP as well as the impact of intervention are needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
Epilepsy is one of the most prevalent neurological diseases. A third of patients with epilepsy remain drug‐resistant. The exact aetiology of drug‐resistant epilepsy (DRE) is still unknown. ...Neuronal tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE.
Methods
For that purpose, cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Post‐mortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases was used as control.
Results
The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100β) followed by flow cytometry analysis. The results were confirmed by image cytometry (ImageStream X Amnis System Cytometer) and with an alternative astrocyte biomarker (NDRG2). Statistical comparison was performed using univariate tests. A total of 22 patients and 10 controls were included. Tetraploid neurons and astrocytes were found both in healthy individuals and DRE patients in the three brain areas analysed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p = 0.020) and astrocytes (p = 0.002) in the hippocampus than controls. These results were validated by image cytometry.
Conclusions
We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects as well as increased levels of both cell populations in DRE patients. Herein, we describe for the first time the presence of tetraploid astrocytes in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment.
We demonstrated the existence of tetraploid astrocytes in healthy human brain. Neural tetraploidy is increased in drug resistant epilepsy patients hippocampus. Astrocytic tetraploidy is higher in drug resistant epilepsy patients hippocampus.
Severe congenital neutropenia (SCN) is characterized by low numbers of peripheral neutrophil granulocytes and a predisposition to life-threatening bacterial infections. We describe a novel genetic ...SCN type in 2 unrelated families associated with recessively inherited loss-of-function mutations in CSF3R, encoding the granulocyte colony-stimulating factor (G-CSF) receptor. Family A, with 3 affected children, carried a homozygous missense mutation (NM_000760.3:c.922C>T, NP_000751.1:p.Arg308Cys), which resulted in perturbed N-glycosylation and aberrant localization to the cell surface. Family B, with 1 affected infant, carried compound heterozygous deletions provoking frameshifts and premature stop codons (NM_000760.3:c.948_963del, NP_000751.1:p.Gly316fsTer322 and NM_000760.3:c.1245del, NP_000751.1:p.Gly415fsTer432). Despite peripheral SCN, all patients had morphologic evidence of full myeloid cell maturation in bone marrow. None of the patients responded to treatment with recombinant human G-CSF. Our study highlights the genetic and morphologic SCN variability and provides evidence both for functional importance and redundancy of G-CSF receptor-mediated signaling in human granulopoiesis.
Rheumatoid arthritis (RA) is a chronic joint autoimmune disease with a higher prevalence of depressive symptoms due to the burden of the disease. There are several patient-self-depression scales used ...for the assessment and a wide range of variations in the prevalence of depression could be related to this. No evidence was found that reports the most accurate, sensitive, and specific depression instrument through an extensive review in the literature. To determine the most precise depression instrument to evaluate RA patients. A systematic review search was directed, considering type of study, prevalence of depressive symptoms, usage of validated depression scales, and reported scale performance measurements. The data extraction followed the PRISMA guidelines, and the risk of bias was assessed using RoB 2, ROBINS-I, and QUADAS-2. From a total of 1958, only 28 articles included in the analysis. The total number of patients analyzed was 6405, with a mean age of 56.53 years, 4474 women (75.22%), and a mean prevalence of depressive symptoms of 27.4%. The most frequent and the best scale used was the CES-D (
n
= 12), considering all characteristics. The CES-D reported the best psychometric properties, and it was the most frequently used tool.
The placement of endotracheal prostheses is a procedure used to treat tracheal lesions when no other surgical options are available. Unfortunately, this technique remains controversial. Both silicon ...and metallic stents are used with unpredictable success rates, as they have advantages but also disadvantages. Typical side effects include restenosis due to epithelial hyperplasia, obstruction and granuloma formation. Repeat interventions are often required. Biodegradable stents are promising in the field of cardiovascular biomechanics but are not yet approved for use in the respiratory system. The aim of the present study is to summarize important information and to evaluate the role of different geometrical features for the fabrication of a new tracheo-bronchial prosthesis prototype, which should be biodegradable, adaptable to the patient’s lesion and producible by 3D printing. A parametric design and subsequent computational analysis using the finite element method is carried out. Two different stent designs are parameterized and analyzed. The biodegradable material chosen for simulations is polylactic acid. Experimental tests are conducted for assessing its mechanical properties. The role of the key design parameters on the radial force of the biodegradable prosthesis is investigated. The computational results allow us to elucidate the role of the pitch angle, the wire thickness and the number of cells or units, among other parameters, on the radial force. This work may be useful for the design of ad hoc airway stents according to the patient and type of lesion.
Seroprevalence of anti-SARS-CoV-2 antibodies is now available in several world regions to better estimate transmission dynamics. However, to date, there is no epidemiological data regarding ...anti-SARS-CoV-2 prevalence in Mexico. Therefore, we aimed to determine the prevalence of anti-SARS-CoV-2 antibodies and define the clinical and demographic characteristics associated with seroprevalence. We conducted a cross-sectional serological survey in Ciudad Guadalupe, NL, Mexico. City government employees voluntarily participated during July 2020. Demographic and clinical characteristics were collected at the time of blood sampling to analyze the associated characteristics. IgM/IgG antibodies were determined using a qualitative chemiluminescent immunoassay. Descriptive statistics were used for categorical and continuous variables. Statistical significance was tested using the Chi-squared test, Student's t-test and the Mann-Whitney. Logistic regression models and the odds ratios (adjusted and unadjusted) were used to estimate the association of demographic and clinical characteristics. Of the 3,268 participants included, 193 (5.9%, 95% CI 5.1-6.8) tested positive for IgM/IgG against SARS-CoV-2. Sex, city of residence, and comorbidities did not show any association with having IgM/IgG antibodies. A total of 114 out of 193 (59.1%) subjects with a positive test were asymptomatic, and the odds of being positive were higher in those who reported symptoms of COVID-19 in the previous four weeks to the survey (OR 4.1, 95% CI 2.9-5.5). There is a low rate of SARS-CoV-2 infection among government employees that have continuously been working during the pandemic. Six in ten infections were asymptomatic, and seroprevalence is low and still far from herd immunity. Epidemiological surveillance and preventive measures should be mandatory.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most potential drugs for the treatment of central nervous system disorders do not cross the blood–brain barrier (BBB). Much research effort has been devoted to the discovery of new BBB‐shuttle ...peptides—most of which have been identified by phage display. Here we report for the first time on the use of phage display against a human BBB cellular model which mimics the characteristics of the BBB. From the panning experiment of a 12‐mer library, the SGVYKVAYDWQH (SGV) peptide sequence was selected and its permeability validated in the aforementioned model. Furthermore, internalization studies suggested that SGV internalizes through a clathrin‐mediated mechanism and that it increases the uptake of a cargo in endothelial cells. These results highlight the usefulness of in vitro BBB models for the discovery of BBB‐shuttle peptides through phage display libraries.
Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive ...astrocytes are found in close association with neuritic plaques; however, the precise role of these glial cells in disease pathogenesis is unknown. In this study, using immunohistochemical techniques and light and electron microscopy, we report that plaque‐associated reactive astrocytes enwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursor protein/presenilin‐1 (APP/PS1) mice. Microglia, the brain phagocytic population, was apparently not engaged in this clearance. Phagocytic reactive astrocytes were present in 35% and 67% of amyloid plaques at 6 and 12 months of age, respectively. The proportion of engulfed dystrophic neurites was low, around 7% of total dystrophies around plaques at both ages. This fact, along with the accumulation of dystrophic neurites during disease course, suggests that the efficiency of the astrocyte phagocytic process might be limited or impaired. Reactive astrocytes surrounding and engulfing dystrophic neurites were also detected in the hippocampus of Alzheimer's patients by confocal and ultrastructural analysis. We posit that the phagocytic activity of reactive astrocytes might contribute to clear dysfunctional synapses or synaptic debris, thereby restoring impaired neural circuits and reducing the inflammatory impact of damaged neuronal parts and/or limiting the amyloid pathology. Therefore, potentiation of the phagocytic properties of reactive astrocytes may represent a potential therapy in Alzheimer's disease.
Main Points
Reactive astrocytes phagocytose dystrophic synapses in Alzheimer's brains.
The phagocytic capacity of astrocytes seems impaired during disease progression and therefore dysfunctional astrocytes are emerging therapeutic targets.
Fanconi anemia is characterized by congenital abnormalities, bone marrow failure, and cancer predisposition. To investigate the origin, functional role, and clinical impact of FANCA mutations, we ...determined a FANCA mutational spectrum with 130 pathogenic alleles. Some of these mutations were further characterized for their distribution in populations, mode of emergence, or functional consequences at cellular and clinical level. The world most frequent FANCA mutation is not the result of a mutational “hot-spot” but results from worldwide dissemination of an ancestral Indo-European mutation. We provide molecular evidence that total absence of FANCA in humans does not reduce embryonic viability, as the observed frequency of mutation carriers in the Gypsy population equals the expected by Hardy-Weinberg equilibrium. We also prove that long distance Alu-Alu recombination can cause Fanconi anemia by originating large interstitial deletions involving FANCA and 2 adjacent genes. Finally, we show that all missense mutations studied lead to an altered FANCA protein that is unable to relocate to the nucleus and activate the FA/BRCA pathway. This may explain the observed lack of correlation between type of FANCA mutation and cellular phenotype or clinical severity in terms of age of onset of hematologic disease or number of malformations.
Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25–30% of epilepsy patients. The main objective is to simultaneously ...describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone (SCEZ), and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array was performed in 19 DR-TLE patients and 10 postmortem non-epileptic controls. Overall, 32, 59, and 3210 differentially methylated probes (DMPs) were associated with DR-TLE in the hippocampus, amygdala, and SCEZ, respectively. These DMP-affected genes were involved in neurotrophic and calcium signaling in the hippocampus and voltage-gated channels in SCEZ, among others. One of the hippocampus DMPs (cg26834418 (
CHORDC1
)) showed a strong blood–brain correlation with BECon and IMAGE-CpG, suggesting that it could be a potential surrogate peripheral biomarker of DR-TLE. Moreover, in three of the top SCEZ’s DMPs (
SHANK3
,
SBF1
, and
MCF2L
), methylation status was verified with methylation-specific qPCR. The differentially methylated CpGs were classified in DMRs: 2 in the hippocampus, 12 in the amygdala, and 531 in the SCEZ. We identified genes that had not been associated to DR-TLE so far such as
TBX5, EXOC7,
and
WRHN
. The area with more DMPs associated with DR-TLE was the SCEZ, some of them related to voltage-gated channels. The DMPs found in the amygdala were involved in inflammatory processes. We also found a potential surrogate peripheral biomarker of DR-TLE. Thus, these results provide new insights into epigenetic modifications involved in DR-TLE.
Graphical Abstract
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