To determine the prevalence of COVID-19 and the characteristics of infected patients, as well as the prevalence of mental disorders associated with the infection and the associated risk factors. ...Secondary: to know the prevalence of the long COVID syndrome and the characteristics of this cohort.
Incidence study of mental disorder in patients diagnosed with COVID-19 and case-control study of long COVID syndrome in the subsample of patients diagnosed with COVID-19 without a history of mental disorder. SITE: Primary care setting in Lleida.
The 46,258 patients diagnosed of COVID-19 without a history of mental disorder were followed for 2 years.
The dependent variable was the mental disorder in the period 03/11/2020 to 03/11/2022; and the independent variables were clinical and social variables. Its association with mental disorder was analyzed by calculating the adjusted hazard ratio using a logistic regression model.
The average age of 46,258 patients at the beginning of the study was 43±17.9 years. 47% were women. The mental disorder rate for all period was 3.46% (59.20% anxiety). A predictive score was elaborated. The long COVID syndrome was more common in older women, without toxic habits, with obesity and associated comorbidity.
COVID-19 has had an impact on the mental health of patients. Knowing the risk factors for developing these mental disorders and the long COVID syndrome would allow the clinician to be able to identify patients at risk in order to establish preventive measures and avoid their appearance.
Introduction. Extreme lateral interbody fusion (XLIF) is a minimally disruptive alternative for anterior lumbar interbody fusion. Recently, synthetic and allograft materials have been increasingly ...used to eliminate donor-site pain and complications secondary to autogenous bone graft harvesting. The clinical use of allograft cellular bone graft has potential advantages over autograft by eliminating the need to harvest autograft while mimicking autograft's biologic function. The objective of this study was to examine 12-month radiographic and clinical outcomes in patients who underwent XLIF with Osteocel Plus, one such allograft cellular bone matrix. Methods. Forty (40) patients were treated at 61 levels with XLIF and Osteocel Plus and included in the analysis. Results. No complications were observed. From preoperative to 12-month postoperative followup, ODI improved 41%, LBP improved 55%, leg pain improved 43.3%, and QOL (SF-36) improved 56%. At 12 months, 92% reported being “very” or “somewhat” satisfied with their outcome and 86% being either “very” or “somewhat likely” to choose to undergo the procedure again. Complete fusion was observed in 90.2% (55/61) of XLIF levels. Conclusions. Complete interbody fusion with Osteocel Plus was shown in 90.2% of XLIF levels, with the remaining 9.8% being partially consolidated and progressing towards fusion at 12 months.
The antiproliferative effect induced by histone deactylase inhibitors (HDACi) is associated with the up-regulated expression of the cyclin-dependent kinase inhibitor p21. Paradoxically, the increased ...expression of p21 correlates with a reduced cell killing to the drug. The direct targeting of p21 is not feasible. An alternate approach could selectively target factors upstream or downstream of p21 that affect one or more specific aspects of p21 function. HDAC inhibitors appear to activate p21 expression via ataxia telangiectasia mutated (ATM) activity. KU60019, a specific ATM inhibitor, has shown to decrease the p21 protein levels in a concentration dependent manner. We explored the potential synergistic interaction of the ATM inhibitor with romidepsin, given the potential complementary impact around p21. A synergistic cytotoxic effect was observed in all lymphoma cell lines examined when the HDACi was combined with KU60019. The increase in apoptosis correlates with decreased expression of p21 due to the ATM inhibitor. KU60019 decreased expression of the cyclin-dependent kinase inhibitor at the transcriptional level, compromising the ability of HDACi to induce p21 and cell cycle arrest and ultimately facilitating a shift toward the apoptotic phase. Central to the increased apoptosis observed when romidepsin is combined with KU60019 is the reduced expression of p21 and the absence of a G2/M cell cycle arrest that would be exploited by the tumor cells to evade the cytotoxic effect of the HDAC inhibitor. We believe this strategy may offer a promising way to identify rational combinations for HDACi directed therapy, improving their activity in malignant disease.
The polymorphism ATG16L1 T300A, associated with increased risk of Crohn’s disease, impairs pathogen defense mechanisms including selective autophagy, but specific pathway interactions altered by the ...risk allele remain unknown. Here, we use perturbational profiling of human peripheral blood cells to reveal that CLEC12A is regulated in an ATG16L1-T300A-dependent manner. Antibacterial autophagy is impaired in CLEC12A-deficient cells, and this effect is exacerbated in the presence of the ATG16L1∗300A risk allele. Clec12a−/− mice are more susceptible to Salmonella infection, supporting a role for CLEC12A in antibacterial defense pathways in vivo. CLEC12A is recruited to sites of bacterial entry, bacteria-autophagosome complexes, and sites of sterile membrane damage. Integrated genomics identified a functional interaction between CLEC12A and an E3-ubiquitin ligase complex that functions in antibacterial autophagy. These data identify CLEC12A as early adaptor molecule for antibacterial autophagy and highlight perturbational profiling as a method to elucidate defense pathways in complex genetic disease.
Display omitted
•Integrated genomics reveals risk-allele-specific autophagy pathway interactions•CLEC12A is important for antibacterial autophagy in epithelial and immune cells•CLEC12A knockdown amplifies antibacterial autophagy defects in ATG16L1∗300A cells•Clec12a−/− mice are more susceptible to Salmonella infection in vivo
Although genome-wide association studies are valuable in identifying disease-associated loci, they produce only a partial view of pathogenesis. Using integrated, systems-level approaches to pinpoint genes that interact with the Crohn’s-disease-associated variant ATG16L1 T300A, Begun et al. identify CLEC12A as an innate defense gene that functions in antibacterial autophagy.
Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. ...However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.
Display omitted
•Microbiomes from multiple GI locations in new-onset Crohn’s disease (CD) cases analyzed•Co-occurring and coexcluded CD-associated organisms identified•Rectal mucosa-associated, but not fecal, microbiome is a robust disease predictor•Antibiotics amplify the dysbiosis associated with CD
Gevers et al. examined the microbiome in the largest pediatric cohort for Crohn’s disease (CD), with samples collected prior to treatment. Irrespective of the location sampled along the gastrointestinal tract, biopsies were found to be a robust disease predictor. Further, antibiotic use amplified the dysbiotic state associated with CD.
•ULCF/LCF is characterized for X52 pipeline steel by smooth and notched specimens.•The theory of critical distances is applied with point, line and area methods.•Point method revealed to be the most ...appropriate for correlating ULCF and LCF data.•Proposed TCD/PM successfully predicted notch bending ULCF test data.
The cyclic failure observed in structural components such as pipelines subjected to extreme loading conditions highlights some limitations concerning the application of existing fatigue damage models. The evaluation and prediction of this type of failure in these steel components under large-scale plastic yielding associated with high levels of stress triaxiality are not sufficiently known nor explored. This fatigue domain is conventionally called ultra-low-cycle fatigue (ULCF) and damage features are representative of both low-cycle fatigue (LCF) and monotonic ductile fracture. Thus, in order to understand the ULCF damage mechanisms both monotonic and LCF tests are required to get representative bounding damage information to model the material damage behaviour under such extreme loading conditions. This paper aims at exploring the Theory of Critical Distances (TCD) in the LCF and ULCF fatigue regimes, including the application of the point, line and area methods. The application of the TCD theories has not been explored so far in the ULCF fatigue regimes, despite its promising results in the LCF and high-cycle fatigue. An experimental program was carried out on several specimens’ geometries made of X52 piping steel. In detail, smooth plane specimens and notched plane specimens were cyclic loaded under tension/compression loading in order to obtain fatigue lives within the range of 101–104 cycles. In addition, cyclic bending tests on notched plane specimens were also incorporated in this study. Finite element simulations of all small-scale tests were conducted allowing to derive elastoplastic stress/strain fields along the potential crack paths. The numerical data were subjected to a post-processing in order to find characteristic lengths that can be treated as a fatigue property according to the TCD. A unified strain-life relation is proposed for the X52 piping steel together with a characteristic material length, consisting of a practical relation for pipeline strain-based design under extreme cyclic loading conditions.
•Feasible route to the production of core/shell nanostructure with pure phases.•Synthesis of CoFe2O4@BiFeO3 core/shell nanoparticles by coprecipitation.•Structural, morphological and magnetic ...properties in CFO@BFO.•Wasp-waisted behavior and exchange bias effect disclosing the coupling between phases.•Spin disorder in CFO@BFO core/shell nanoparticles.
We synthesize CoFe2O4@BiFeO3 core/shell nanoparticles by coprecipitation and systematically investigate the structural, morphological, and magnetic properties in such nanostructured system. Through structural and morphological characterization, we demonstrate the obtainment of core/shell nanostructure with pure phases. By performing a broad experimental magnetic analysis, we evaluate the magnetic response for the precursor phases, as well as for the core/shell nanostructure. For this latter, we identify fingerprints of the wasp-waisted behavior and exchange bias effect, disclosing the exchange coupling between the phases taking place at the interface. Further, we reveal the exchange coupling between core and shell is strongly affected by a spin glass behavior arisen from the spin disorder in the CoFe2O4@BiFeO3 core/shell nanoparticles. After all, our findings allow us to place the used procedures taking into account the coprecipitation and calcination processes as a feasible route to the production of high-quality core/shell nanostructures.
Fungi are consistently enriched in inflamed intestines, with elusive effects on host immunity. In a recent issue of Nature Medicine, Martini et al. identify a subset of Th1 cells able to lyse the ...epithelium, enriched in Crohn's disease patient samples after fungal exposure.
Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of ...environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies.
Display omitted
Display omitted
•HFGP cohort: host/environment, genetics, and microbiome affect cytokine production•IFN-γ and IL-22, but not IL-17 and Mo-derived cytokine responses, decrease with age•Gender affects cytokine responses, resulting in disease susceptibility differences•Cytokine responses are season dependent, influenced by AAT concentrations
As part of the Human Functional Genomics Project, mapping of environmental and non-genetic host factors reveals critical associations between age, gender, and annual seasonality in inter-individual variability of immune cell function.
PDF
