Comparative metabarcoding and biodiversity of gut-associated fungal assemblages of Dendroctonus species (Curculionidae: Scolytinae).

The genus Dendroctonus is a Holarctic taxon composed of 21 nominal species; some of these species are well known in the world as disturbance agents of forest ecosystems. Under the bark of the host tree, these insects are involved in complex and dynamic associations with phoretic ectosymbiotic and endosymbiotic communities. Unlike filamentous fungi and bacteria, the ecological role of yeasts in the bark beetle holobiont is poorly understood, though yeasts were the first group to be recorded as microbial symbionts of these beetles. Our aim was characterize and compare the gut fungal assemblages associated to 14 species of Dendroctonus using the internal transcribed spacer 2 (ITS2) region. A total of 615,542 sequences were recovered yielding 248 fungal amplicon sequence variants (ASVs). The fungal diversity was represented by 4 phyla, 16 classes, 34 orders, 54 families, and 71 genera with different relative abundances among Dendroctonus species. The α-diversity consisted of 32 genera of yeasts and 39 genera of filamentous fungi. An analysis of ß-diversity indicated differences in the composition of the gut fungal assemblages among bark beetle species, with differences in species and phylogenetic diversity. A common core mycobiome was recognized at the genus level, integrated mainly by Candida present in all bark beetles, Nakazawaea, Cladosporium, Ogataea, and Yamadazyma. The bipartite networks confirmed that these fungal genera showed a strong association between beetle species and dominant fungi, which are key to maintaining the structure and stability of the fungal community. The functional variation in the trophic structure was identified among libraries and species, with pathotroph-saprotroph-symbiotroph represented at the highest frequency, followed by saprotroph-symbiotroph, and saprotroph only. The overall network suggested that yeast and fungal ASVs in the gut of these beetles showed positive and negative associations among them. This study outlines a mycobiome associated with Dendroctonus nutrition and provides a starting point for future in vitro and omics approaches addressing potential ecological functions and interactions among fungal assemblages and beetle hosts.

Survival Analysis of Male Patients with Brain Metastases at Initial Breast Cancer Diagnosis over the Last Decade.

Breast cancer in men represents approximately 1% of all breast cancer diagnoses. Among all patients with breast cancer, approximately 30% will develop brain metastases. Over the past decade, there have been multiple advances in the treatment of metastatic breast cancer; however, long-term outcomes of this presentation in male patients are lacking. We evaluated male patients with de novo stage IV breast cancer using the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2019. Overall survival (OS) was estimated using the Kaplan-Meier method and differences between groups were compared using log rank tests. In total, 22 male patients with brain metastases at initial breast cancer diagnosis were included. Patients with HR-positive/HER2-negative tumors had the longest OS (median 13 months). Factors associated with shorter overall survival were advanced age, unmarried marital status, lower household income, and grade III disease, among others. Brain metastases remains an unmet medical need for patients with breast cancer; the development of new drugs may provide an improvement in overall survival for male patients in the future.

Survival analysis of patients with brain metastases at initial breast cancer diagnosis over the last decade.

PURPOSE: There have been significant advances in the treatment of metastatic breast cancer (BC) over the past years, and long-term outcomes after a diagnosis of brain metastases are lacking. We aimed to identify predictors of brain metastases at initial breast cancer diagnosis, describe overall survival (OS) in the past decade, and identify factors associated with OS after brain metastases diagnosis. METHODS: We evaluated patients with de novo stage IV BC using the Surveillance, Epidemiology and End Results database from 2010 to 2019. Multivariate logistic regression was conducted to assess predictors of brain metastases at initial breast cancer diagnosis. OS was estimated using the Kaplan-Meier method and log rank test was used to compare differences between groups. Cox regression was used to assess associations between several variables and OS. RESULTS: 1,939 patients with brain metastases at initial breast cancer diagnosis were included. Factors associated with this presentation were grade III/IV tumors, ductal histology, hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-positive subtype, and extracranial metastases. Patients with HR-positive/HER2-positive disease had the longest OS (median 18 months) and 12.2% were alive at 8 years. Factors associated with shorter OS included older age, lower income, triple-negative subtype, higher grade, and visceral metastases. CONCLUSION: Over the last decade, the median OS of patients with brain metastases at initial breast cancer diagnosis remained poor; however, a substantial minority survive 5 or more years, with rates higher in patients with HER2-positive tumors. In addition to tumor subtype, OS varied according to age, extracranial metastases, and sociodemographic factors.

Associations between Toxoplasma gondii seropositivity and psychopathological manifestations in schizophrenic patients: A single-center study from Ecuador.

BACKGROUND: Schizophrenia, a complex neuropsychiatric disorder, is believed to be influenced by various factors including environmental exposures. A potential environmental factor is the infection by the obligate intracellular parasitic protozoan, Toxoplasma gondii which affects neurotransmitter levels, which could potentially exacerbate, trigger symptoms of schizophrenia or make them worst. OBJECTIVE: To investigate the association between Toxoplasma gondii seropositivity and psychopathological presentation in persons with schizophrenia in Ecuador. METHODS: This study was conducted at the Neuroscience Institute of Guayaquil, Ecuador. Among 368 inpatients, 104 were selected based on specific inclusion and exclusion criteria. Descriptive statistics captured patient characteristics and mental health outcomes. Logistic regression models estimated the effect of toxoplasmosis on various mental health outcomes, controlling for demographic and health-related variables. RESULTS: 86.5% of participants were seropositive for toxoplasmosis. Toxoplasma-seropositive schizophrenic patients had a lower risk of depression but a significantly higher risk of disorientation. The most prevalent mental health outcomes were Language Impairments (70.2%) and Bizarre Behavior (76.0%). CONCLUSION: Our findings suggest that Toxoplasma gondii seropositivity may have specific effects on mental functions in schizophrenic patients, particularly reducing the risk of depression but increasing the risk of disorientation. Further studies are required to clarify these associations and the potential underlying mechanisms.

Synaptic remodeling of GluA1 and GluA2 expression in the nucleus accumbens promotes susceptibility to cognitive deficits concomitant with downstream GSK3ß mediated neurotoxicity in female mice during abstinence from voluntary oral methamphetamine.

Stimulant-use disorders can present with long-term cognitive and mental health deficits. Little is known about the underlying molecular mechanisms perpetuating sex differences in cognitive and behavioral deficits in preclinical models of addiction to stimulants such as methamphetamine (MA). The current study investigated the neurochemical shifts underlying sex disparities in MA-induced working memory deficits and an addictive phenotype following abstinence from chronic MA abuse. We used our previously reported mouse model of voluntary oral methamphetamine administration (VOMA) consisting of an acquisition phase (days 1-14) characterized by escalating doses of MA and a binge phase (days 14-28) characterized by static doses. Female VOMA mice exhibited sustained MA consumption during the binge phase, demonstrating sex-specific vulnerabilities to the maintenance of MA addiction. The 8-arm radial maze was used to test spatial working memory performance following abstinence from VOMA. Results indicate working memory deficits correlated to higher MA consumption in females only. Hippocampal and accumbal tissue were collected and analyzed by immunoblotting. Female VOMA mice had decreased GluA1, but not GluA2, in the hippocampus, which may perpetuate synaptic destabilization and working memory deficits. Female-specific increases in GluA1 and p-GSK3ß expression in accumbal tissue suggest vulnerability toward abstinence-induced drug craving and heightened downstream neurotoxicity. Our study reveals female-specific neurochemical shifts in hippocampal and accumbal AMPA receptor signaling following abstinence from chronic MA consumption that may perpetuate female susceptibility to MA-induced cognitive deficits. These data demonstrate a novel molecular pathway that would exacerbate memory deficits and perpetuate an addictive phenotype in female populations following MA abuse.

Treatments for breast cancer in men: late effects and impact on quality of life.

PURPOSE: Male breast cancer accounts for approximately 1% of all breast cancer diagnoses. Unfortunately, a lack of information exists regarding late effects of breast cancer treatment in men. METHODS: An online survey directed towards male breast cancer patients was distributed via social medial and emails from June to July 2022. Participants were asked about their disease characteristics, treatments and side effects from the disease or treatment. Patients and treatment variables were reported via descriptive statistics. Univariate logistic regression was performed to evaluate associations between different treatment variables and outcomes expressed by odds ratio. RESULTS: A total of 127 responses were analyzed. Median age of the participants was 64 years (range 56-71 years). A total of 91 participants (71.7%) revealed they experienced late effects secondary to their cancer or cancer treatment. The most concerning physical and psychological symptoms reported were fatigue and fear of recurrence respectively. Axillary lymph node dissection was associated with swollen arm and with difficulty in arm or shoulder movement. Systemic chemotherapy was related to bothersome hair loss and changes on interest in sex; and endocrine therapy was associated with feeling less masculine. CONCLUSION: Our study showed that men suffer several late effects from treatments for breast cancer. Lymphedema, difficulty with arm and shoulder movement, sexual dysfunction and hair loss should be discussed with males as it can be distressing for some patients and decrease their quality of life.

Rapid Onset Severe Immune Thrombocytopenia following mRNA COVID-19 Vaccine in a Young Patient.

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people around the world. Vaccination against COVID-19 has been approved for the following three vaccines in the United States: Pfizer-BioNTech, Moderna, and Janssen. Hematological complications of vaccination have been reported in the literature but remain as a rare phenomenon. We present the case of a patient who developed severe thrombocytopenia within twenty-four hours following the Pfizer-BioNTech vaccination. Commonly encountered differentials including heparin-induced thrombocytopenia and common viral etiologies were ruled out, and other causes such as drug reactions deemed unlikely as the etiology of this presentation after a broad workup. Nucleocapsid antibodies against COVID-19 were found to be positive which indicated that vaccination was at least the second encounter with this virus for our patient, which has been reported previously as the cause of immune thrombocytopenia (ITP), and this might be the culprit for sudden onset. He responded to the first-line ITP treatment with corticosteroids and intravenous immunoglobulin (IVIG) as evidenced by the fast recovery of platelet count and lack of recurrence of thrombocytopenia.

Militarismo y militarización en Venezuela: ¿juego de veridicción? / Militarism and militarization in Venezuela: veridiction game?

En el marco de los conceptos desarrollados por Michel Foucault sobre el estatuto histórico de la verdad, juegos de verdad o veridicción, y sobre la condición del discurso del saber, figuras epistemológicas, se analiza en este ensayo el discurso académico de los últimos veinte años en torno a la situación de la institución militar en Venezuela. En particular, se intenta desentrañar el régimen de veridicción de ese campo discursivo que se sostiene sobre la multiplicidad de nociones que se construyen a partir de las de militarismo y militarización.

Comparative genomics and interactomics of polyadenylation factors for the prediction of new parasite targets: Entamoeba histolytica as a working model.

Protein-protein interactions (PPI) play a key role in predicting the function of a target protein and drug ability to affect an entire biological system. Prediction of PPI networks greatly contributes to determine a target protein and signal pathways related to its function. Polyadenylation of mRNA 3'-end is essential for gene expression regulation and several polyadenylation factors have been shown as valuable targets for controlling protozoan parasites that affect human health. Here, by using a computational strategy based on sequence-based prediction approaches, phylogenetic analyses, and computational prediction of PPI networks, we compared interactomes of polyadenylation factors in relevant protozoan parasites and the human host, to identify key proteins and define potential targets for pathogen control. Then, we used Entamoeba histolytica as a working model to validate our computational results. RT-qPCR assays confirmed the coordinated modulation of connected proteins in the PPI network and evidenced that silencing of the bottleneck protein EhCFIm25 affects the expression of interacting proteins. In addition, molecular dynamics simulations and docking approaches allowed to characterize the relationships between EhCFIm25 and Ehnopp34, two connected bottleneck proteins. Interestingly, the experimental identification of EhCFIm25 interactome confirmed the close relationships among proteins involved in gene expression regulation and evidenced new links with moonlight proteins in E. histolytica, suggesting a connection between RNA biology and metabolism as described in other organisms. Altogether, our results strengthened the relevance of comparative genomics and interactomics of polyadenylation factors for the prediction of new targets for the control of these human pathogens.

Eddy Current Measurement for Planar Structures.

Eddy current (EC) testing has become one of the most common techniques for measuring metallic planar structures in various industrial scenarios such as infrastructures, automotive, manufacturing, and chemical engineering. There has been significant progress in measuring the geometry, electromagnetic properties, and defects of metallic planar structures based on electromagnetic principles. In this review, we summarize recent developments in EC computational models, systems, algorithms, and measurement approaches for planar structures. First, the computational models including analytical models, numerical methods, and plate property estimation algorithms are introduced. Subsequently, the impedance measurement system and probes are presented. In plate measurements, sensor signals are sensitive to probe lift-off, and various algorithms for reducing the lift-off effect are reviewed. These approaches can be used for measureing thickness and electromagnetic properties. Furthermore, defect detection for metallic plates is also discussed.

Unique hepatic manifestations of COVID-19-induced immune dysregulation in children.

The two cases we present are the first to demonstrate novel manifestations of COVID-19 related interaction between the liver and the immune system in pediatric patients. Written informed consent was obtained from the parent/guardian to publish this report in accordance with the journal's patient consent policy.

Advances in the Management of Central Nervous System Metastases from Breast Cancer.

Central nervous system (CNS) metastases are common in breast cancer (BC) patients and are particularly relevant as new treatments for BC are prolonging survival. Here, we review advances in the treatment of CNS metastases from BC, including radiotherapy, systemic therapies, and the evolving role of immunotherapy. The use of radiotherapy and chemotherapy is the cornerstone of treatment for CNS metastases. However, new targeted therapies have recently been developed, including anti-HER2 agents and antibody-drug conjugates that have presented promising results for the treatment of these patients.

Identification of two potential aetiological agents of chronic diarrhoea in an immunocompromised patient in Cuba using conventional and molecular diagnostic techniques.

The aetiology of diarrhoea in a patient in Cuba with HIV was investigated. Although molecular diagnostics are still not used in many under-resourced settings, here traditional methods were supported by use of PCR. This approach enabled detection of a dual infection (Cystoisospora belli and Enterocytozoon bieneusi), the latter of which was not identified by microscopy with Didier's trichromic staining.

Voluntary oral methamphetamine increases memory deficits and contextual sensitization during abstinence associated with decreased PKMζ and increased κOR in the hippocampus of female mice.

BACKGROUND: Female populations exhibit vulnerabilities to psychostimulant addiction, as well as cognitive dysfunction following bouts of abuse. AIMS: The goal for this study was to advance our understanding of the mechanisms that produce sex disparities in drug addiction. METHODS: We used an animal model for voluntary oral methamphetamine administration (VOMA) and focused on male and female mice that consumed 7.6-8.2 mg/kg of methamphetamine (MA) per day during the last 18 days of the paradigm. RESULTS: The VOMA-exposed female mice displayed increased locomotor activity in the drug-administration context compared to male mice, demonstrating sex-specific changes in contextual sensitization. During 2 weeks of forced abstinence, mice underwent further behavioral testing. We show that abstinence increased open-arm entries on the elevated plus maze in both sexes. There were no differences in immobility on the tail suspension test. In a hippocampal-dependent radial arm maze task, VOMA-treated female mice, but not male mice, showed working memory deficits. Hippocampal tissue was collected and analyzed using Western blotting. VOMA-exposed female mice exhibited increased kappa opioid receptor (κOR) expression in the hippocampus compared to male mice, suggesting a vulnerability toward abstinence-induced dysphoria. Female VOMA mice also exhibited a decrease in the memory protein marker, protein kinase M zeta (PKMζ), in the hippocampus. CONCLUSIONS: Our study reveals sex-specific effects following abstinence from chronic MA consumption on hippocampal κOR and PKMζ expression, suggesting that these neural changes in female mice may underlie spatial memory deficits and identify an increased susceptibility to dysregulated neural mechanisms. These data validate VOMA as a model sensitive to sex differences in behavior and hippocampal neurochemistry following chronic MA exposure.

The Insomnia-Addiction Positive Feedback Loop: Role of the Orexin System.

Significant sleep impairments often accompany substance use disorders (SUDs). Sleep disturbances in SUD patients are associated with poor clinical outcomes and treatment adherence, emphasizing the importance of normalizing sleep when treating SUDs. Orexins (hypocretins) are neuropeptides exclusively produced by neurons in the posterior hypothalamus that regulate various behavioral and physiological processes, including sleep-wakefulness and motivated drug taking. Given its dual role in sleep and addiction, the orexin system represents a promising therapeutic target for treating SUDs and their comorbid sleep deficits. Here, we review the literature on the role of the orexin system in sleep and drug addiction and discuss the therapeutic potential of orexin receptor antagonists for SUDs. We argue that orexin receptor antagonists may be effective therapeutics for treating addiction because they target orexin's regulation of sleep (top-down) and motivation (bottom-up) pathways.

Prevalence and Persistence of Cost-Related Medication Nonadherence Among Medicare Beneficiaries at High Risk of Hospitalization.

Importance: The unaffordability of drugs has been a persistent and elusive challenge in the US health care system. Little is known about the prevalence and persistence of cost-related medication nonadherence (CRN) in a population with high-cost, high-need resource utilization. Objective: To evaluate the prevalence and persistence of CRN among Medicare beneficiaries at high risk of hospitalization as well as the characteristics associated with CRN in this population. Design, Setting, and Participants: This cohort study used survey data from Medicare patients at high risk of hospitalization and with a life expectancy greater than 12 months at an urban academic medical center from November 6, 2012, to January 30, 2018. Patients were followed up for 12 months at 3-month intervals from baseline, for a total of 5 surveys. Data were analyzed from September 1, 2020, to January 5, 2021. Main Outcomes and Measures: Self-reported CRN, using a metric of persistence and transiency. Based on the results of the 5 surveys, CRN was categorized as persistent (3 or more surveys), intermittent (2), transient (1), and any (1 or more). Multiple logistic regression analyses were used to evaluate factors associated with persistent and transient CRN. Results: Of the 1655 Medicare beneficiaries followed up during the 15-month study period, 1036 (62.6%) were women and 1452 (87.7%) were Black or African American; 769 (46.5%) were younger than 65 years, and 886 (53.5%) were 65 years or older (mean [SD] age, 62.4 [15.9] years). A total of 374 patients (22.6%) reported CRN at baseline, 810 (48.9%) reported any CRN, and 230 (13.9%) reported persistent CRN (148 [19.2%] of those younger than 65 years and 82 [9.3%] of those 65 years or older). The 230 patients who had persistent CRN accounted for 28% of those who reported CRN at least once during the 15-month study period. Younger age (eg, <50 years vs 75 years: adjusted odds ratio [AOR], 3.07; 95% CI, 1.61-5.86; P = .001), worse self-reported health (AOR, 1.59; 95% CI, 1.10-2.31; P = .01), and depression (AOR, 1.58; 95% CI, 1.11-2.24; P = .01) were associated with greater likelihood of persistent CRN. The population-adjusted prevalence of CRN was 53.6% (887 patients). Conclusions and Relevance: The findings suggest that CRN is prevalent, moderately persistent, and variable in the Medicare population at high risk of hospitalization despite coverage by insurance. Longitudinal follow-up and refined predictive modeling of CRN appear to be needed to identify and target more precisely those with persistent CRN and to develop effective interventions.

Evaluating the capacity of species distribution modeling to predict the geographic distribution of the mangrove community in Mexico.

Mangroves are highly productive ecosystems that provide important environmental services, but have been impacted massively in recent years by human activities. Studies of mangroves have focused on their ecology and function at local or landscape scales, but little has been done to understand their broader distributional patterns or the environmental factors that determine those distributions. Species distribution models (SDMs), have been used to estimate potential distributions of hundreds of species, yet no SDM studies to date have assessed mangrove community distributions in Mexico (the country with the fourth largest extent of this ecosystem). We used maximum entropy approaches to model environmental suitability for mangrove species distributions in the country, and to identify the environmental factors most important in determining those distributions. We also evaluated whether this modeling approach is adequate to estimate mangrove distribution as a community across Mexico. Best models were selected based on statistical significance (AUC ratio), predictive performance (omission error of 5%), and model complexity (Akaike criterion); after this evaluation, only one model per species met the three evaluation criteria. Environmental variable sets that included distance to coast yielded significantly better models; variables with strongest contributions included elevation, temperature of the coldest month, and organic carbon content of soil. Based on our results, we conclude that SDMs can be used to map mangrove communities in Mexico, but that results can be improved at local scales with inclusion of local variables (salinity, hydroperiod and microtopography), field validations, and remote sensing data.