To evaluate the rate of recurrence among patients with pheochromocytomas and sympathetic paragangliomas (PGLs; together PPGLs) and to identify predictors of recurrence (local recurrence and/or ...metastatic disease).
This retrospective multicenter study included information of 303 patients with PPGLs in follow-up in 19 Spanish tertiary hospitals. Recurrent disease was defined by the development of local recurrence and/or metastatic disease after initial complete surgical resection.
A total of 303 patients with PPGLs that underwent 311 resections were included (288 pheochromocytomas and 15 sympathetic PGLs). After a median follow-up of 4.8 years (range 1-19), 24 patients (7.9%) had recurrent disease (3 local recurrence, 17 metastatic disease and 4 local recurrence followed by metastatic disease). The median time from the diagnosis of the PPGL to the recurrence was of 11.2 months (range 0.5-174) and recurrent disease cases distributed uniformly during the follow-up period. The presence of a pathogenic variant in
gene (hazard ratio HR 13.3, 95% CI 4.20-41.92), higher urinary normetanephrine levels (HR 1.02 per each increase in standard deviation, 95% CI 1.01-1.03) and a larger tumor size (HR 1.01 per each increase in mm, 95% CI 1.00-1.02) were independently associated with disease recurrence.
The recurrence of PPGLs occurred more frequently in patients with
mutations, with larger tumors and with higher urinary normetanephrine levels. Since PPGL recurrence may occur at any time after the initial PPGL diagnosis is performed, we recommend performing a strict follow-up in all patients with PPGLs, especially in those patients with a higher risk of recurrent disease.
Molecular regulation was initially assumed to follow both a unidirectional and a hierarchical organization forming pathways. Regulatory processes, however, form highly interlinked networks with ...non-hierarchical and non-unidirectional structures that contain statistically overrepresented circuits or motifs. Here, we analyze the behavior of pathways containing non-unidirectional (i.e. bidirectional) and non-hierarchical interactions that create motifs. In comparison with unidirectional and hierarchical pathways, our pathways have a high diversity of behaviors, characterized by the size and number of attractors. Motifs have been studied individually showing that feedback circuit motifs regulate the number and size of attractors. It is less clear what happens in molecular networks that usually contain multiple feedbacks. Here, we find that the way feedback circuits couple to each other (i.e., the combination of the functionalities of feedback circuits) regulate both the number and size of the attractors. We show that the different expected results of epistasis analysis (a method to infer regulatory interactions) are produced by many non-hierarchical and non-unidirectional structures. Thus, these structures cannot be correctly inferred by epistasis analysis. Finally, we show that the combinations of functionalities, combined with other network properties, allow for a better characterization of regulatory structures.
Introduction:
Several reports have emerged describing the long-term consequences of COVID-19 and its effects on multiple systems.
Methods:
As further research is needed, we conducted a longitudinal ...observational study to report the prevalence and associated risk factors of the long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal).
Results:
We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p < 0.00001). Women were more prone than men to develop long-term symptoms, and invasive mechanical ventilation also increased the frequency of symptoms at 30 days post-discharge.
Conclusion:
Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.
Objetivo: En el marco del proyecto de extensión solidaria universitaria “Laboratorio de salud rural e intercultural comunidad de Bojayá, Chocó”, este artículo presenta los resultados correspondientes ...a la fase de diagnóstico individual y la aproximación inicial al diagnóstico colectivo de la situación de salud presente en un colectivo afrocolombiano sobreviviente a una masacre emblemática ocurrida en Colombia. Metodología: Exploración preliminar y elementos de diagnóstico comunitario con 66 sobrevivientes de la masacre del 2 de mayo de 2002 en el poblado de Bellavista, en el municipio de Bojayá, Chocó. Resultados: Se identificaron condiciones socioeconómicas deficientes, diagnósticos clínicos desatendidos, y se efectuó la aproximación inicial a potencialidades disponibles para el afrontamiento de las necesidades en salud individuales y colectivas de la población abordada, representadas en saberes comunitarios y posibilidad de acceso a programas y servicios institucionales en salud para víctimas. Conclusiones: Pese a que transcurrieron más de 15 años desde el momento de ocurrencia de la masacre de Bojayá hasta nuestro trabajo con la comunidad, se encontró persistencia de múltiples necesidades insatisfechas que afectan negativamente la situación de salud individual y colectiva, sin adecuada ni oportuna intervención. Cualquier acción futura que se plantee para atender tales asuntos debe tomar en cuenta las condiciones histórico-sociales que configuran los procesos de salud-enfermedad-cuidado en dicha comunidad.
Transmission is a driver of tuberculosis (TB) epidemics in high-burden regions, with assumed negligible impact in low-burden areas. However, we still lack a full characterization of transmission ...dynamics in settings with similar and different burdens. Genomic epidemiology can greatly help to quantify transmission, but the lack of whole genome sequencing population-based studies has hampered its application. Here, we generate a population-based dataset from Valencia region and compare it with available datasets from different TB-burden settings to reveal transmission dynamics heterogeneity and its public health implications. We sequenced the whole genome of 785 Mycobacterium tuberculosis strains and linked genomes to patient epidemiological data. We use a pairwise distance clustering approach and phylodynamic methods to characterize transmission events over the last 150 years, in different TB-burden regions. Our results underscore significant differences in transmission between low-burden TB settings, i.e., clustering in Valencia region is higher (47.4%) than in Oxfordshire (27%), and similar to a high-burden area as Malawi (49.8%). By modeling times of the transmission links, we observed that settings with high transmission rate are associated with decades of uninterrupted transmission, irrespective of burden. Together, our results reveal that burden and transmission are not necessarily linked due to the role of past epidemics in the ongoing TB incidence, and highlight the need for in-depth characterization of transmission dynamics and specifically tailored TB control strategies.
We put forward a theoretical and dynamical approach for the semi-quantitative analysis of CD4+ T cell differentiation, the process by which cells with different functions are derived from activated ...CD4
T naïve lymphocytes in the presence of particular cytokine microenvironments. We explore the system-level mechanisms that underlie CD4+ T plasticity-the conversion of polarized cells to phenotypes different from those originally induced.
In this paper, we extend a previous study based on a Boolean network to a continuous framework. The network includes transcription factors, signaling pathways, as well as autocrine and exogenous cytokines, with interaction rules derived using fuzzy logic.
This approach allows us to assess the effect of relative differences in the concentrations and combinations of exogenous and endogenous cytokines, as well as of the expression levels of diverse transcription factors. We found either abrupt or gradual differentiation patterns between observed phenotypes depending on critical concentrations of single or multiple environmental cytokines. Plastic changes induced by environmental cytokines were observed in conditions of partial phenotype polarization in the T helper 1 to T helper 2 transition. On the other hand, the T helper 17 to induced regulatory T-cells transition was highly dependent on cytokine concentrations, with TGFβ playing a prime role.
The present approach is useful to further understand the system-level mechanisms underlying observed patterns of CD4
T differentiation and response to changing immunological challenges.
It has been proposed that the onset of Acquired Thrombotic Thrombocytopenic Purpura (iTTP) is more severe than subsequent relapses; however, existing studies have limitations. We conducted a ...retrospective observational study to compare analytical and clinical severity of onset and relapse aTTP cases between 2012 and 2023. A total of 370 episodes of aTTP were analyzed, comprising 272 at initial diagnosis and 98 relapses. At onset, analytical parameters indicative of severity (low hemoglobin, low platelet count, and increased LDH) were significantly worse; patients had severe neurological symptoms (
p
<0.001) and ≥ 3 points in the TMA mortality score (
p
<0.001). In conclusion, the onset of aTTP is associated with worse analytical parameters and severe neurological involvement.
The β2 integrin CD11b/CD18, also known as complement receptor 3 (CR3), and the moonlighting protein aminopeptidase N (CD13), are two myeloid immune receptors with overlapping activities: adhesion, ...migration, phagocytosis of opsonized particles, and respiratory burst induction. Given their common functions, shared physical location, and the fact that some receptors can activate a selection of integrins, we hypothesized that CD13 could induce CR3 activation through an inside-out signaling mechanism and possibly have an influence on its membrane expression. We revealed that crosslinking CD13 on the surface of human macrophages not only activates CR3 but also influences its membrane expression. Both phenomena are affected by inhibitors of Src, PLCγ, Syk, and actin polymerization. Additionally, after only 10 min at 37 °C, cells with crosslinked CD13 start secreting pro-inflammatory cytokines like interferons type 1 and 2, IL-12p70, and IL-17a. We integrated our data with a bioinformatic analysis to confirm the connection between these receptors and to suggest the signaling cascade linking them. Our findings expand the list of features of CD13 by adding the activation of a different receptor via inside-out signaling. This opens the possibility of studying the joint contribution of CD13 and CR3 in contexts where either receptor has a recognized role, such as the progression of some leukemias.
The study of stool microbiota has taken great relevance in the last years, given its role in the maintenance of the intestinal metabolic, physiological, and immunological homeostasis, as well as, its ...effect over HIV biomarkers levels such as CD4/CD8 ratio, high sensitivity C-Reactive Protein (hs-CRP), related to poor outcomes (rapid progression to AIDS). Several efforts have been made to characterize the gut microbiome. In HIV infection, most of the studies report the presence of a dysbiotic pattern; however, few of them have made an approach in elderly HIV-positive subjects despite the fact that nowadays this subgroup is rising. In this study, we compared the composition of faecal microbiota, Short Chain Fatty Acids (SCFAs), and systemic biomarkers between elderly HIV-positive and HIV-negative subjects.
A cross-sectional study with 18 HIV-negative controls and 20 HIV-positive patients. The quantification of Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, Lactobacillus, Enterobacteriaceae, Bifidobacterium, Escherichia coli, Clostridium leptum, Clostridium coccoides was performed in faecal samples by qPCR. The analysis was performed by calculating the ΔCq of each microorganism using 16S rDNA as a reference gene. Faecal SCFAs were measured by HPLC. The hs-CRP and sCD14 were performed by ELISA.
An increase in the Firmicutes/Bacteroidetes ratio, coupled with a significant increase in the proteobacteria phylum was detected in HIV-positive subjects. In contrast, a decrease in the Clostridium leptum group was observed. Nevertheless, these elderly HIV-positive patients showed higher levels of total SCFAs mainly by an augmented propionic acid values, compared to HIV-negative subjects. Whereas high levels of hs-CRP were positively correlated with sCD14 in the HIV-positive group.
Alterations in bacterial communities reveals a dysbiotic state related to an unbalance of faecal SCFAs. Therefore, these intestinal conditions might drive an increase of poor prognostic biomarkers in elderly HIV-positive subjects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patient from India with fever and uncommon findings Vergara, Andrea; Fernandez-Pittol, Mariana José; Gutierrez-Fornes, Cristina ...
Enfermedades infecciosas y microbiologia clinica (English ed.),
06/2019, Letnik:
37, Številka:
6
Journal Article
Recenzirano
Odprti dostop
A 28-years-old male patient from India that had not travelled to his country in the last nine months presented to the emergency room with general discomfort, dysthermia feeling, sweating, chills, and ...shivering. In the physical examination, temperature was quantified in 40.5 °C. No neurological deficit or peripheral lymphadenopathy was found. Blood was taken and sent to the local laboratory for examination and then sent to our hospital in order to confirm the diagnosis. This sample was stored for almost 3 days at room temperature.
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