On the origin of alkali feldspar megacrysts in granitoids. Part 2: evidence for nucleation and growth under magmatic conditions from crystal size distributions of the Cathedral Peak Granodiorite, California, USA.

The mechanisms whereby alkali feldspar megacrysts form have been debated for several decades; yet, we do not understand well the processes that lead to their formation. We take advantage of glacially polished outcrop surfaces from the Cathedral Peak Granodiorite in the Tuolumne Intrusive Complex, CA to quantitatively characterize alkali feldspar textures, to provide better insight into their origin. On the glacially polished surfaces, we traced alkali feldspar crystals > 10 mm in the field. From the same localities, we also collected large slabs and stained them to reveal feldspar textures for crystals < 20 mm in size. We scaned the resulting field tracings and rock slabs to quantify CSDs using image processing techniques with the software ImageJ. The CSDs from glacially polished outcrop surfaces and complementary polished and stained rock slabs reveal two stages of crystallization. Crystals > 20 mm show log-linear CSDs with shallow slopes, suggesting magmatic nucleation and growth on timescales of thousands of years. Crystals < 20 mm define a second stage of crystallization, with much steeper slopes, suggesting a period of enhanced nucleation leading to formation of a groundmass during the final stages of solidification on timescales of decades to centuries. We do not find any evidence for CSDs affected by textural coarsening, or any effects of subsolidus processes. Our data suggest that these megacrysts form in large, slowly cooling magma, where low nucleation rates dominate. These crystals are not special in their magmatic formation-only in their size. A change in solidification conditions led to the formation of a groundmass, which warrants further study to better understand this crystallization stage in a plutonic environment.

Mapping Conformational Changes in the Saliva Proteome Potentially Associated with Oral Cancer Aggressiveness.

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.

Alkene 1,3-Difluorination via Transient Oxonium Intermediates.

The 1,3-difunctionalization of unactivated alkenes is an under-explored transformation that leads to moieties that are otherwise challenging to prepare. Herein, we report a hypervalent iodine-mediated 1,3-difluorination of homoallylic (aryl) ethers to give unreported 1,3-difluoro-4-oxy groups with moderate to excellent diastereoselectivity. The transformation proceeds through a different mode of reactivity for 1,3-difunctionalization, in which a regioselective addition of fluoride opens a transiently formed oxonium intermediate to rearrange an alkyl chain. The optimized protocol is scalable and shown to proceed well with a variety of functional groups and substitution on the alkenyl chain, hence providing ready access to this fluorinated, conformationally controlled moiety.

Antarctica's hidden mycoviral treasures in fungi isolated from mosses: A first genomic approach.

This study investigates the presence of mycoviruses in Antarctic fungi and elucidates their evolutionary relationships. To achieve this, we aligned mycoviral gene sequences with genomes of previously sequenced Antarctic endophytic fungi, made available by our research group and accessible via Joint Genome Institute. Our findings reveal that the most prevalent genetic regions in all endophytic fungi are homologous to Partitiviruses, Baculoviridae, and Phycodnaviridae. These regions display evidence of positive selection pressure, suggesting genetic diversity and the accumulation of nonsynonymous mutations. This phenomenon implies a crucial role for these regions in the adaptation and survival of these fungi in the challenging Antarctic ecosystems. The presence of mycoviruses in Antarctic endophytic fungi may indicate shared survival strategies between the virus and its host, shedding light on their evolutionary dynamics. This study underscores the significance of exploring mycoviruses within endophytic fungi and their contributions to genetic diversity. Future research avenues could delve into the functional implications of these conserved mycoviral genetic regions in Antarctic endophytic fungi, providing a comprehensive understanding of this intriguing association and genomic retention of viral region in fungi.

Relapsing Plasmodium vivax malaria in a 12-year-old Brazilian girl: A case report.

Plasmodium vivax causes the vast majority of malaria cases in Brazil. The lifecycle of this parasite includes a latent stage in the liver, the hypnozoite. Reactivation of hypnozoites induces repeated relapses. We report a case of two relapses of vivax malaria in a teenage girl after conventional treatment with chloroquine and primaquine. Chloroquine prophylactic treatment for three months was prescribed with a favourable outcome of the case.

Profiling of Tumor-Infiltrating Immune Cells and Their Impact on Survival in Glioblastoma Patients Undergoing Immunotherapy with Dendritic Cells.

Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection. An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival. In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.

Investigation of the nutritional and functional roles of a combinational use of xylanase and ß-glucanase on intestinal health and growth of nursery pigs.

BACKGROUND: Xylanase and ß-glucanase combination (XG) hydrolyzes soluble non-starch polysaccharides that are anti-nutritional compounds. This study aimed to evaluate the effects of increasing levels of XG on intestinal health and growth performance of nursery pigs. METHODS: Forty pigs (6.5 ± 0.4 kg) were assigned to 5 dietary treatments and fed for 35 d in 3 phases (11, 9, and 15 d, respectively). Basal diets mainly included corn, soybean meal, and corn distiller's dried grains with solubles, contained phytase (750 FTU/kg), and were supplemented with 5 levels of XG at (1) 0, (2) 280 TXU/kg xylanase and 125 TGU/kg ß-glucanase, (3) 560 and 250, (4) 840 and 375, or (5) 1,120 and 500, respectively. Growth performance was measured. On d 35, all pigs were euthanized and jejunal mucosa, jejunal digesta, jejunal tissues, and ileal digesta were collected to determine the effects of increasing XG levels and XG intake on intestinal health. RESULTS: Increasing XG intake tended to quadratically decrease (P = 0.059) viscosity of jejunal digesta (min: 1.74 mPa·s at 751/335 (TXU/TGU)/kg). Increasing levels of XG quadratically decreased (P < 0.05) Prevotellaceae (min: 0.6% at 630/281 (TXU/TGU)/kg) in the jejunal mucosa. Increasing XG intake quadratically increased (P < 0.05) Lactobacillaceae (max: 40.3% at 608/271 (TXU/TGU)/kg) in the jejunal mucosa. Increasing XG intake quadratically decreased (P < 0.05) Helicobacteraceae (min: 1.6% at 560/250 (TXU/TGU)/kg) in the jejunal mucosa. Increasing levels of XG tended to linearly decrease (P = 0.073) jejunal IgG and tended to quadratically increase (P = 0.085) jejunal villus height to crypt depth ratio (max: 2.62 at 560/250 (TXU/TGU)/kg). Increasing XG intake tended to linearly increase the apparent ileal digestibility of dry matter (P = 0.087) and ether extract (P = 0.065). Increasing XG intake linearly increased (P < 0.05) average daily gain. CONCLUSIONS: A combinational use of xylanase and ß-glucanase would hydrolyze the non-starch polysaccharides fractions, positively modulating the jejunal mucosa-associated microbiota. Increased intake of these enzyme combination possibly reduced digesta viscosity and humoral immune response in the jejunum resulting in improved intestinal structure, and ileal digestibility of nutrients, and finally improving growth of nursery pigs. The beneficial effects were maximized at a combination of 550 to 800 TXU/kg xylanase and 250 to 360 TGU/kg ß-glucanase.

Atenção primária à saúde: a maior aliada na resposta à epidemia da dengue no Brasil

Em resposta ao cenário epidemiológico crítico de incidên- cia de casos, hospitalizações e óbitos por dengue, o Ministério da Saúde do Brasil incorporou, ainda em dezembro de 2023, a vacina contra a dengue no Calendário Nacional de Vacinação. Inicialmente, a vacina foi incorporada para crianças e adolescen- tes de 10 a 14 anos (1), faixa etária que concentra o maior número de hospitalizações pela doença depois das pessoas idosas — para quem, no entanto, a vacina não foi liberada pela Agência Nacional de Vigilância Sanitária (Anvisa). Nesse sentindo, o Brasil tornou-se o primeiro país do mundo a disponibilizar a vacina contra a dengue de forma gratuita no serviço público de saúde, juntamente com diversos métodos de controle vetorial.

Comparison of arterial hypotension incidence during general anesthesia induction - target-controlled infusion vs. bolus injection of propofol: a randomized clinical trial.

BACKGROUND: The incidence of arterial hypotension during induction of general anesthesia is influenced by the method of propofol administration, but there is a dearth of randomized clinical trials comparing bolus injection and target-controlled infusion in relation to arterial hypotension. This study seeks to compare the incidence of arterial hypotension between these two methods of propofol administration. METHODS: This prospective, randomized, single-center, non-blinded study included 60 patients (aged 35 to 55 years), classified as ASA physical status I or II, who were undergoing non-cardiac surgeries. They were randomly allocated using a computer to two groups based on the method of propofol administration during the induction of general anesthesia: the Target Group, receiving target-controlled infusion at 4 µg.mL-1, and the Bolus Group, receiving a bolus infusion of 2 mg.kg-1. Both groups also received midazolam 2 mg, fentanyl 3 µg.kg-1, and rocuronium 0.6 mg.kg-1. Over the first 10 minutes of anesthesia induction, Mean Arterial Pressure (MAP), Heart Rate (HR), level of Consciousness (qCON), and Suppression Rate (SR) were recorded every 2 minutes. RESULTS: Twenty-seven patients remained in the TCI group, while 28 were in the Bolus group. Repeated measure analysis using mixed-effects models could not reject the null hypothesis for the effect of group-time interactions in MAP (p = 0.85), HR (p = 0.49), SR (p = 0.44), or qCON (p = 0.72). The difference in means for qCON (60.2 for TCI, 50.5 for bolus, p < 0.001), MAP (90.3 for TCI, 86.2 for bolus, p < 0.006), HR (76.2 for TCI, 76.9 for bolus, p = 0.93), and SR (0.01 for TCI, 5.5 for bolus, p < 0.001), irrespective of time (whole period means), revealed some significant differences. CONCLUSION: Patients who received propofol bolus injection exhibited a lower mean arterial pressure, a greater variation in the level of consciousness, and a higher suppression rate compared to those who received it as a target-controlled infusion. However, the interaction effect between groups and time remains inconclusive.

MMP-1, MMP-8, and MMP-13 Gene Polymorphisms and Haplotype Is a Risk Factor for Dupuytren Contracture: A Case-Control Study.

BACKGROUND: There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. METHODS: A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. RESULTS: The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. CONCLUSIONS: In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

Longitudinal attenuation in political polarization: Evidence from COVID-19 vaccination adherence in Brazil.

BACKGROUND: While political polarization in policy opinions, preferences, and observance is well established, little is known about whether and how such divisions evolve, and possibly attenuate, over time. Using the COVID-19 pandemic in Brazil as the backdrop, we examine the longitudinal evolution of a highly relevant and polarizing policy: adherence to the COVID-19 vaccination. METHODS: Studies 1 (N = 3346) and 2 (N = 10,214) use nationwide surveys to document initial differences and subsequent changes in vaccination adherence between conservatives ("Bolsonaristas") and non-conservatives ("non-Bolsonaristas"). Study 3 (N = 742) uses an original dataset to investigate belief changes among conservatives and their association with asymmetric changes in vaccination adherence. RESULTS: Despite substantial differences at the early stages of rollout, the gap in vaccination adherence between conservatives and non-conservatives significantly decreased with the passage of time, driven essentially by a much faster uptake among the initially most skeptic-the conservatives. Study 3 demonstrates that the asymmetric changes in vaccination adherence were associated with meaningful belief changes among the conservatives, especially about the perceived effectiveness of the COVID-19 vaccines and the expected adherence of peers to the vaccination campaign. CONCLUSIONS: Together, these studies show that, in a context where the superiority of the promoted policy becomes clear over time and individuals have the opportunity to revisit prior beliefs, even intense political polarization can be attenuated.

Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review.

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications.

Cost-effective 3D lung tissue spheroid as a model for SARS-CoV-2 infection and drug screening.

BACKGROUND: The SARS-CoV-2 pandemic has spurred an unparalleled scientific endeavor to elucidate the virus' structure, infection mechanisms, and pathogenesis. Two-dimensional culture systems have been instrumental in shedding light on numerous aspects of COVID-19. However, these in vitro systems lack the physiological complexity to comprehend the infection process and explore treatment options. Three-dimensional (3D) models have been proposed to fill the gap between 2D cultures and in vivo studies. Specifically, spheroids, composed of lung cell types, have been suggested for studying SARS-CoV-2 infection and serving as a drug screening platform. METHODS: 3D lung spheroids were prepared by coculturing human alveolar or bronchial epithelial cells with human lung stromal cells. The morphology, size, and ultrastructure of spheroids before and after SARS-CoV-2 infection were analyzed using optical and electron microscopy. Immunohistochemistry was used to detect spike protein and, thus, the virus presence in the spheroids. Multiplex analysis elucidated the cytokine release after virus infection. RESULTS: The spheroids were stable and kept their size and morphology after SARS-CoV-2 infection despite the presence of multivesicular bodies, endoplasmic reticulum rearrangement, tubular compartment-enclosed vesicles, and the accumulation of viral particles. The spheroid responded to the infection releasing IL-6 and IL-8 cytokines. CONCLUSION: This study demonstrates that coculture spheroids of epithelial and stromal cells can serve as a cost-effective infection model for the SARS-CoV-2 virus. We suggest using this 3D spheroid as a drug screening platform to explore new treatments related to the cytokines released during virus infection, especially for long COVID treatment.

Platynosomum (Trematoda: Dicrocoeliidae) infection in barn owls (Tyto alba) in Northeastern Brazil.

Platynosomum spp. are parasites that inhabit the gallbladder and bile ducts of various mammals and birds worldwide. Most studies of Platynosomum spp. in birds focus on the observation and morphological characterization of the parasite through parasitological or molecular examinations, with scarce literature describing anatomopathological alterations, mainly histopathological. We report the case of a male barn owl infected with Platynosomum spp.. At necropsy, the barn owl showed dilation with parasites and fibrosis of the intrahepatic bile ducts and gallbladder. Microscopically, it was possible to identify trematodes in the bile ducts associated with a lymphoplasmacytic inflammatory infiltrate. The morphological structures of the worms were described on histopathology and direct examination. The presence of parasitism that is usually cosmopolitan in wild animals represents a risk to the biodiversity of fauna in the region, as well as a warning about the spread and maintenance of the biological cycle of the worm in humans and domestic animals.

Towards Automation in 3D Cell Culture: Selective and Gentle High-Throughput Handling of Spheroids and Organoids via Novel Pick-Flow-Drop Principle.

3D cell culture is becoming increasingly important for mimicking physiological tissue structures in areas such as drug discovery and personalized medicine. To enable reproducibility on a large scale, automation technologies for standardized handling are still a challenge. Here, a novel method for fully automated size classification and handling of cell aggregates like spheroids and organoids is presented. Using microfluidic flow generated by a piezoelectric droplet generator, aggregates are aspirated from a reservoir on one side of a thin capillary and deposited on the other side, encapsulated in free-flying nanoliter droplets to a target. The platform has aggregate aspiration and plating efficiencies of 98.1% and 98.4%, respectively, at a processing throughput of up to 21 aggregates per minute. Cytocompatibility of the method is thoroughly assessed with MCF7, LNCaP, A549 spheroids and colon organoids, revealing no adverse effects on cell aggregates as shear stress is reduced compared to manual pipetting. Further, generic size-selective handling of heterogeneous organoid samples, single-aggregate-dispensing efficiencies of up to 100% and the successful embedding of spheroids or organoids in a hydrogel with subsequent proliferation is demonstrated. This platform is a powerful tool for standardized 3D in vitro research.

Fluoxetine alters rat's milk properties causing impact on offspring's development.

Fluoxetine is an antidepressant used to treat several conditions including postpartum depression. This disease causes cognitive, emotional, behavioral and physical changes, negatively affecting the mother, child and family life. However, fluoxetine is excreted in breast milk, causing short and long-term effects on children who were exposed to the drug during lactation, so studies that seek to uncover the consequences of these effects are needed. Thus, the aim of this study was to evaluate the effects of fluoxetine on the nutritional characteristics of milk and on growth and neurobehavioral development of the offspring on a rat model. Lactating rats were divided into 4 groups: control group and three experimental groups, which were treated with different doses of fluoxetine (1, 10 and 20 mg/kg) during the lactation. Dams body weight and milk properties were measured, as well as offspring's growth and physical and neurobehavioral development. Results showed that the use of fluoxetine during lactation decreased dam's body weight and alters milk's properties, leading to a decrease in offspring's growth until adulthood. Therefore, the use of fluoxetine during lactation needs to be cautiously evaluated, with the benefits to the mothers and the associated risk to the offspring carefully balance.

The bladder microbiota is not significantly altered by intravesical BCG therapy.

INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, n = 32) or benign prostatic hyperplasia (control group, n = 41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.

Do calves hide after birth? Postpartum behavior of dairy calves and their dams housed in individual calving pens.

Under near-natural conditions, domesticated dairy calves hide the first days after birth before cow and calf join the herd. In commercial dairy production, an opportunity to seclude from the herd after parturition is rarely given. This study aimed to investigate the effect of providing a covered area in an individual calving pen on maternal and neonatal calf behavior. Forty-six cow-calf pairs were housed in either an individual uncovered calving pen with 4 open sides or an individual partially covered calving pen with 3 covered sides, providing a secluded area for the cow and calf. Calf position in the pen, maternal behavior, and proximity between the cow and calf were recorded for the first 72 h after birth using instantaneous sampling at 5-min intervals. Data were analyzed using linear mixed effect models. The duration of maternal sniffing and licking, the duration of time the cow spent standing with her head over the calf, and the time spent in close proximity to the calf were higher during the first 24 h after birth compared with later days, reflecting intense maternal behavior during this early period. Calves did not show a preference for staying in the covered side of the pen. Calves in covered pens received more maternal sniffing and licking, indicating that the provision of cover postpartum facilitated maternal behavior and the formation of the maternal-filial bond the first few days after birth.