Studies specifically designed to determine the profile of psychiatric symptoms among COVID-19 patients are limited and based on case series, self-report questionnaires, and surveys. The objective of ...the study was to identify and classify the neuropsychological symptoms of hospitalized COVID-19 patients during the first wave of the pandemic in one of the most important front-line tertiary hospitals from Spain, and to analyze its correlation with diagnosed mental disorders, as well as to explore potential risk factors associated with mental health problems. This observational, cohort study involved data from COVID-19 patients at the University Hospital 12 de Octubre (Madrid, Spain) from February to May 2020. First, patients underwent a semistructured phone interview (screening phase), based on the Mini International Neuropsychiatric Interview (MINI). Then the confirmation of the diagnosis (confirmation phase) was performed in patients who reported a mental disorder development or worsening. A factorial analysis was performed to identify groups of symptoms. A tetrachoric matrix was created, and factorial analysis, by a principal component analysis, was employed upon it. Factors showing values >1.0 were selected, and a varimax rotation was applied to these factors. Symptoms most frequently identified in patients were anosmia/ageusia (54.6%), cognitive complaints (50.3%), worry/nervousness (43.8%), slowing down (36.2%), and sadness (35.4%). Four factors were identified after the screening phase. The first ("anxiety/depression") and second ("executive dysfunction") factors explained 45.4 and 11.5% of the variance, respectively. Women, age between 50 and 60 years, duration in the hospital (more than 13 days), and psychiatric history showed significant higher levels (number of symptoms) in the factors. This study reports the factor structure of the psychiatric symptoms developed by patients with a confirmed diagnosis of SARS-CoV2 during the first wave of the COVID-19. Three item domains (anxiety, depression, and posttraumatic stress disorder symptoms) were loaded together on one factor, whereas sleep disturbance stood up as a separate factor. Interestingly, the item anosmia/ageusia was not captured by any factor. In conclusion, an increase in neuropsychiatric morbidity is expected in the upcoming months and years. Therefore, screening for early symptoms is the first step to prevent mental health problems associated with this pandemic.
Thanks to technological advances, the administration of cognitive assessments
via
digital solutions continues to increase, both in research and clinical practice. “Guttmann Cognitest”
°ledR
is a ...digital solution for cognitive assessment which includes seven computerized tasks designed to assess main cognitive functions requiring approximately 20 min to be completed. The purpose of the present study was to validate it against standard and more extensive in-person neuropsychological assessments in the context of the Barcelona Brain Health Initiative (BBHI) cohort study. We studied 274 participants of the BBHI (126 women, mean age = 56.14, age range 44–69), who underwent an extensive in-person assessment, including a classical paper-and-pencil neuropsychological assessment and a cognitive assessment
via
the “Guttmann Cognitest”
°ledR
. Principal component analysis indicated that “Guttmann Cognitest”
°ledR
measures four main cognitive domains and convergent validity analysis demonstrated that cognitive performance was associated with gold standard paper and pencil tests. Results also showed an expected negative correlation with age, a relation with educational level as well as a gender effect. Regression-based norming equations for the sample tested are also reported. Performing a cognitive assessment with this digital solution is feasible and potentially useful to gather information about cognitive functioning in large samples and experimental settings.
Increased levels of reactive oxygen species (ROS) and a low-grade chronic inflammation in multiple organs have been demonstrated in obesity. Morus alba leaves extracts (MAEs) have been used in ...traditional medicine as anti-inflammatory agents. In this work, the bioactive compounds of different genotypes of M. alba L. (Filipina, Valenciana Temprana, Kokuso, and Italia) were analyzed not only by reverse phase high performance liquid chromatography–electrospray ionization-time of flight-mass spectrometry (RP-HPLC-ESI-TOF-MS) and hydrophilic interaction chromatography–electrospray ionization-time of flight-mass spectrometry (HILIC-ESI-TOF-MS), but also screened for in vitro and in vivo antioxidant activity by means of DPPH• radical scavenging assay and Caenorhabditis elegans model. These MAEs were administered daily in a model of diet-induced obesity in mice. Filipina and Italia genotypes significantly reduced weight gain, the glycemic levels in high fat diet, as well as, levels of LDL-cholesterol and triglycerides. Filipina and Italia MAEs also reduced the expression of proinflammatory mediators such as Tnf-α, Il-1β, Il-6 and increased the levels of adiponectin and AMPK, which exert anti-inflammatory effects. Moreover, Italia genotype ameliorated the intestinal barrier function. In conclusion, Filipina and Italia methanolic extracts show the highest antioxidant and anti-inflammatory effect, due to the presence of compounds such as protocatechuic acid or quercetin-3-glucoside, and they could be developed as a complementary treatment for obesity and metabolic disorders.
Aims
Amyloid precursor protein (APP) 𝛽‐C‐terminal fragment (𝛽CTF) may have a neurotoxic role in Alzheimer's disease (AD). 𝛽CTF accumulates in the brains of patients with sporadic (SAD) and genetic ...forms of AD. Synapses degenerate early during the pathogenesis of AD. We studied whether the 𝛽CTF accumulates in synapses in SAD, autosomal dominant AD (ADAD) and Down syndrome (DS).
Methods
We used array tomography to determine APP at synapses in human AD tissue. We measured 𝛽CTF, A𝛽40, A𝛽42 and phosphorylated tau181 (p‐tau181) concentrations in brain homogenates and synaptosomes of frontal and temporal cortex of SAD, ADAD, DS and controls.
Results
APP colocalised with pre‐ and post‐synaptic markers in human AD brains. APP 𝛽CTF was enriched in AD synaptosomes.
Conclusions
We demonstrate that 𝛽CTF accumulates in synapses in SAD, ADAD and DS. This finding might suggest a role for 𝛽CTF in synapse degeneration. Therapies aimed at mitigating 𝛽CTF accumulation could be potentially beneficial in AD.
Using array tomography in post‐mortem brain tissue from the temporal and frontal cortex, we found that APP is located in synaptic compartments in different forms of AD. We also describe that APP βCTF accumulates in synaptosomal fractions in different forms of AD and that this accumulation correlates with Aβ and tau concentrations.
Gasdermin (GSDM)-mediated pyroptosis is functionally involved in multiple diseases, but Gasdermin-B (GSDMB) exhibit cell death-dependent and independent activities in several pathologies including ...cancer. When the GSDMB pore-forming N-terminal domain is released by Granzyme-A cleavage, it provokes cancer cell death, but uncleaved GSDMB promotes multiple pro-tumoral effects (invasion, metastasis, and drug resistance). To uncover the mechanisms of GSDMB pyroptosis, here we determined the GSDMB regions essential for cell death and described for the first time a differential role of the four translated GSDMB isoforms (GSDMB1-4, that differ in the alternative usage of exons 6-7) in this process. Accordingly, we here prove that exon 6 translation is essential for GSDMB mediated pyroptosis, and therefore, GSDMB isoforms lacking this exon (GSDMB1-2) cannot provoke cancer cell death. Consistently, in breast carcinomas the expression of GSDMB2, and not exon 6-containing variants (GSDMB3-4), associates with unfavourable clinical-pathological parameters. Mechanistically, we show that GSDMB N-terminal constructs containing exon-6 provoke cell membrane lysis and a concomitant mitochondrial damage. Moreover, we have identified specific residues within exon 6 and other regions of the N-terminal domain that are important for GSDMB-triggered cell death as well as for mitochondrial impairment. Additionally, we demonstrated that GSDMB cleavage by specific proteases (Granzyme-A, Neutrophil Elastase and caspases) have different effects on pyroptosis regulation. Thus, immunocyte-derived Granzyme-A can cleave all GSDMB isoforms, but in only those containing exon 6, this processing results in pyroptosis induction. By contrast, the cleavage of GSDMB isoforms by Neutrophil Elastase or caspases produces short N-terminal fragments with no cytotoxic activity, thus suggesting that these proteases act as inhibitory mechanisms of pyroptosis. Summarizing, our results have important implications for understanding the complex roles of GSDMB isoforms in cancer or other pathologies and for the future design of GSDMB-targeted therapies.
The herein work analyzes the compositional and structural modification of extracted lignins from both barley and wheat straws biologically pretreated with Streptomyces by solid-state fermentation ...with two different strains, MDG147 and MDG301. The results showed that the MDG301 strain promoted major lignin solubilization, especially for wheat straw and alkaline extraction, and simultaneously exhibited a higher hydrolytic enzymatic profile than MDG147. Furthermore, the substrates were submitted to soda pulping, and the chemical composition and structural characteristics of the extracted soda-lignins were analyzed by analytical standard methods, Fourier transform infrared spectroscopy, thermogravimetric analysis, and nuclear magnetic resonance. Generally, soda-lignins showed high purity, with the remaining carbohydrate content in agreement with enzymatic patterns. Moreover, Streptomyces strains produced structural modifications, including a major degradation of β-alkyl-aryl ether and C–C linkages of soda-lignins, as well as an enrichment of syringyl units. Furthermore, these modifications also increased the hydroxyl group content, increasing entanglement possibilities and H-bonding. The obtained soda-lignins were focused on as binders for the adhesive formulation, showing excellent adhesion results. Those adhesives based on lignin coming from barley straw exhibited the best performance in shear strength tests, whereas those extracted from wheat straw provided the maximum values in peeling essays.
The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized ...records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor.
In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course.
Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease.
As the world population continues to age, the prevalence of neurological diseases, such as dementia, poses a significant challenge to society. Detecting cognitive impairment at an early stage is ...vital in preserving and enhancing cognitive function. Digital tools, particularly mHealth, offer a practical solution for large-scale population screening and prompt follow-up assessments of cognitive function, thus overcoming economic and time limitations.
In this work, two versions of a digital solution called Guttmann Cognitest
were tested.
Two hundred and one middle-aged adults used the first version (Group A), while 132 used the second one, which included improved tutorials and practice screens (Group B). This second version was also validated in an older age group (Group C).
This digital solution was found to be highly satisfactory in terms of usability and feasibility, with good acceptability among all three groups. Specifically for Group B, the system usability scale score obtained classifies the solution as the best imaginable in terms of usability.
Guttmann Cognitest
has been shown to be effective and well-perceived, with a high potential for sustained engagement in tracking changes in cognitive function.
One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of ...the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data.
Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/μL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve.
Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.
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