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In Chile, the arrival of immigrant students has had significant consequences for teachers, who have had to adapt quickly and with few resources to a new school reality. This makes it relevant to study variables affecting their attitudes towards immigrant students. This work aimed to determine the role of outgroup anxiety and intercultural sensitivity in the relationship between cultural threat and attitudes toward multiculturalism at school in a sample of 190 primary and secondary education teachers. A sequential mediation model was carried out. Outcomes show the direct effect of cultural threat on teachers’ attitudes towards multiculturalism at school, as well as its indirect effects through outgroup anxiety and intercultural sensitivity. The model explains 55% of the variability of the dependent variable. Results stress the importance of attending to the socio cognitive and emotional processes affecting teachers’ beliefs and attitudes regarding immigrant students to facilitate teaching work and school relationships.

Introduction: Iodine is an essential mineral for fetal growth and brain development. The aim of this research was to evaluate goiter, iodine deficiency and intrauterine growth restriction in pregnant women of minority ethnic groups in Colombia. Methods: A cross-sectional study was performed in six non-metropolitan areas of Colombia. Results: A total of 318 Indigenous and Afro-descendant pregnant women were invited to participate: 248 (83.2%) Indigenous and 50 (16.8%) Afro-descendants were studied. The mean age was 24 years (range 13-44 years). Of the women, 130 (43.5%) were from the department of Cauca, 72 (24.1%) were from Córdoba, 28 (9.4%) were from Guajira, 26 (8.8%) were from Sierra Nevada de Santa Marta, 22 (7.4%) were from Amazonas, 16 (5.4%) were from Meta and 4 (1.3%) were from the department of Cesar. A total of 244 (81.8%) were illiterate and 291 (97.7%) were of very low socioeconomic level. Goiter was observed in 69 (23.3%) pregnant women (38 (41.7%) from the department of Cauca, 10 (35.7%) from Guajira, 5 (31.2%) from Meta, 6 (27.2%) from Amazonas and 10 (13.8%) from Córdoba). Iodine deficiency (

Background: Gastroschisis is the most common congenital defect of the abdominal wall. Its incidence has increased by 2 to 10 times worldwide. However, morbidity and mortality rates vary between high-, medium-, and low-income countries. Methods: This is an observational, cross-sectional study aimed at establishing the prevalence of gastroschisis in babies admitted to the intensive care units of the Clinica Versalles and the Hospital Universitario del Valle (HUV). Additionally, it is analytical, as it seeks to identify the clinical and surgical factors associated with the mortality of these neonates. Data were collected based on the information already recorded in the clinical histories of patients born or referred to these institutions between January 2018 and June 2022. Results: Fifty-six (56) babies were evaluated, with a birth rate corresponding to 1/1,000 live births. Of these, 35.70% were born to mothers under 19 years old, 55.36% came from municipalities other than Cali, and 91.07% were born at a gestational age greater than 32 weeks. Additionally, 58.90% were girls, with a median weight of 2,167 g (range: 1,440–3,240 g). Among the evaluated babies, 25% presented with complicated gastroschisis, and 44.64% had other malformations. The association between mortality outcomes and clinical factors showed that invasive mechanical ventilation for longer than 7 days increased the probability of death by 7.94 times, sepsis by 8.35 times, pulmonary hypertension by 7.14 times, acute kidney injury by 8.87 times, and pneumonia by 7.14 times. The surgical factors significantly associated with mortality were abdominal compartment syndrome (13.67 times), staged closure (9.17 times), more than two surgical interventions (7.80 times), failure to achieve closure (30.71 times), post-surgical complications (5.29 times), and intestinal ischemia (43 times). Conclusion: The rate of gastroschisis in this study is notably higher than that reported in other countries, with a substantial number of clinical and surgical complications significantly associated with mortality. Key factors influencing mortality include prolonged invasive mechanical ventilation, sepsis, pulmonary hypertension, acute kidney injury, and pneumonia. Surgical factors such as abdominal compartment syndrome, staged closure, multiple surgical interventions, failure to achieve closure, post-surgical complications, and intestinal ischemia also greatly increase the risk of death.

Abstract Background Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. Methods Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. Discussion This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. Trial registration NCT05301283. Trial status The trial started recruitment on March 17, 2022.

Objectives Stereotactic body radiotherapy (SBRT) is widely used for localized prostate cancer and implementation of MR-guided radiotherapy has the advantage of tighter margins and improved sparing of organs at risk. Here we evaluate outcomes and time required to treat using non-adaptive MR-guided SBRT (MRgSBRT) for localized prostate cancer at our institution. Methods From 9/2019 to 11/2021 we conducted a retrospective review of 80 consecutive patients who were treated with MRgSBRT to the prostate. Patients included low (LR) (5%), favorable intermediate (FIR) (40%), unfavorable intermediate (UIR) (49%), and high risk (HR) (6%). Short-term androgen deprivation therapy was used in 32% of patients. Target volumes included prostate gland and proximal seminal vesicles with an isotropic 3 mm margin. Treatment was prescribed to 36.25 Gy in 5 fractions every other day with urethral sparing. Hydrogel spacer was used in 18% of patients. Time on the linac was recorded as beam on time (BOT) plus total treatment time (TTT) including gating. Analyzed outcomes included PSA response and patient reported outcomes scored by the American Urological Association (AUA) questionnaire and toxicity per CTCAE v5. General linear regression model was used to analyze factors affecting PSA and AUA in longitudinal follow up, and chi-square test was used to assess factors affecting toxicity. Results Median follow up was 19.3 months (3.8 – 36.6). Median BOT was 4.6 min (2.6 – 7.2) with a median TTT of 11 min (7.6 – 15.8). Pre-treatment vs post-RT median PSA was 6.36 (2.20 – 19.6) vs 0.85 (0.19 – 3.6), respectively ( P < 0.001). PSA decrease differed significantly when patients were stratified by risk category, favoring LR/FIR vs UIF/HR group ( P = 0.019). Four (5%) patients experienced a biochemical failure (BCF), with a median time to BCF of 20.4 months (7.9 – 34.5). Median biochemical failure free survival (BCFFS) was not reached, with 2-yr and 4-yr BCFFS of 97.1% and 72.1%, respectively. Patients with LR/FIR disease had 100% 2-yr and 4-yr BCFFS, whereas patients with UIF/HR had 95% and 41% 2-yr and 4-yr BCFFS ( P = 0.05). Mean pre-treatment AUA was 7.3 (1 - 25) vs 11.3 (1 - 26) at first follow-up; however, AUA normalized to baseline over time. Urethral Dmax ≥35 Gy trended to lower AUA score at all follow-ups ( P = 0.07). Forty-one (51%) patients reported grade 1-2 genitourinary toxicities at the 1 month follow up. Grade 3 toxicity (proctitis) was noted in 1 patient. There was no decrease in any grade rectal toxicity with use of hydrogel spacer (3 vs 6, P = 0.2). No grade ≥4 toxicities was observed. Conclusions MRgSBRT has the potential for treatment adaptation but this comes at the cost of increased resource utilization. Our experience with non-adaptive MRgSBRT of the prostate highlights its short treatment times as well as efficacy with good PSA control and low toxicity profile.

ABSTRACT Clostridioides difficile (C. difficile) is widely distributed in the intestinal tract of humans, animals, and in the environment. It is the most common cause of diarrhea associated with the use of antimicrobials in humans and among the most common healthcare-associated infections worldwide. Its pathogenesis is mainly due to the production of toxin A (TcdA), toxin B (TcdB), and a binary toxin (CDT), whose genetic variants may be associated with disease severity. We studied genetic diversity in 39 C. difficile isolates from adults and children attended at two Mexican hospitals, using different gene and genome typing methods and investigated their association with in vitro expression of toxins. Whole-genome sequencing in 39 toxigenic C. difficile isolates were used for multilocus sequence typing, tcdA, and tcdB typing sequence type, and phylogenetic analysis. Strains were grown in broth media, and expression of toxin genes was measured by real-time PCR and cytotoxicity in cell-culture assays. Clustering of strains by genome-wide phylogeny matched clade classification, forming different subclusters within each clade. The toxin profile tcdA+/tcdB+/cdt+ and clade 2/ST1 were the most prevalent among isolates from children and adults. Isolates presented two TcdA and three TcdB subtypes, of which TcdA2 and TcdB2 were more prevalent. Prevalent clades and toxin subtypes in strains from children differed from those in adult strains. Toxin gene expression or cytotoxicity was not associated with genotyping or toxin subtypes. In conclusion, genomic and phenotypic analysis shows high diversity among C. difficile isolates from patients with healthcare-associated diarrhea.IMPORTANCEClostridioides difficile is a toxin-producing bacterial pathogen recognized as the most common cause of diarrhea acquired primarily in healthcare settings. This bacterial species is diverse; its global population has been divided into five different clades using multilocus sequence typing, and strains may express different toxin subtypes that may be related to the clades and, importantly, to the severity and progression of disease. Genotyping of children strains differed from adults suggesting toxins might present a reduced toxicity. We studied extensively cytotoxicity, expression of toxins, whole genome phylogeny, and toxin typing in clinical C. difficile isolates. Most isolates presented a tcdA+/ tcdB+/cdt+ pattern, with high diversity in cytotoxicity and clade 2/ST1 was the most prevalent. However, they all had the same TcdA2/TcdB2 toxin subtype. Advances in genomics and bioinformatics tools offer the opportunity to understand the virulence of C. difficile better and find markers for better clinical use

Pyriproxyfen is an insecticide currently employed in numerous countries for the management of agricultural and indoor pests. Several studies indicate that this insecticide has been detected in multiple rivers, with concentrations reaching as high as 99.59 ng/L in the Júcar River in Spain. Therefore, the determination of some biochemical and genetic effects of this insecticide on aquatic organisms could serve as an early warning mechanism to identify potential disruptions in various biomarkers. Based on this, Daphnia magna organisms were exposed to pyriproxyfen sublethal concentrations for 21 days. Some biochemical parameters, including cholesterol, triglycerides, glucose, lactate, and LDH activity, were determined. Additionally, some genetic biomarkers associated with oxidative stress, heat shock proteins, lipid metabolism, hemoglobin, metallothioneins, and vitellogenin synthesis were evaluated in daphnids exposed to the insecticide for 21 days. LDH activity increased significantly in those daphnids exposed to the highest insecticide concentration (14.02 µg/L), while cholesterol levels decreased significantly. In contrast, glucose, total proteins, and triglycerides remained unaffected in D. magna exposed to pyriproxyfen. On the other hand, exposure to the insecticide led to notable alterations in gene expression among individuals. Specifically, genes associated with lipid metabolism and reproduction exhibited a significant reduction in gene expression. Fabd expression was decreased by approximately 20% in exposed daphnids, while vtg expression was suppressed as much as 80% when compared to control values. Furthermore, it was observed that the hgb1 and hgb2 genes, associated with hemoglobin synthesis, exhibited significant overexpression. Notably, the dysfunction observed in both hemoglobin genes was linked to an increase in pigmentation in Daphnia magna during the course of the experiment. These alterations in gene expression could serve as effective indicators of early contamination even at low pesticide concentrations.

The literature has consistently found that victims of intimate partner violence (IPV) against women are reluctant to make their situation visible and report it to the police. Whether victims perceive and define IPV behaviors as reportable is key to understanding in which cases the police are seen as potential providers of help or whether other potential sources of help (family, friends, professionals, etc.) are preferred. The purpose of the present study was to analyze the influence of perceived reportability of IPV on women’s selection of the police as a source of help compared to not seeking help or selecting other sources of help. Structural equation modeling was applied to data from 479 female participants drawn from a nationally representative sample of 1,112 male and female Chilean adolescents and young adults conducted by the National Youth Institute of Chile. The results showed that perceived reportability was a significant predictor of choosing the police as a source of help compared to other informal sources of help, such as family and friends. However, perceived reportability did not affect help-seeking choices between the police and other formal help sources (psychologists, public services). Participants’ IPV victimization and attitudes toward IPV also played a specific role in selecting the police as a source of help. These findings highlight the complexity of the visibility of women’s IPV victimization to the police and the need to examine its explanatory mechanisms.

Objective: Describe the device-associated infections in the NICUs in Cali – Colombia, a middle-income country, between August 2016 to December 2018. Methods: Observational cross-sectional study evaluating reports of device-associated infections in 10 NICUs in Cali, Colombia, between August 2016 and December 2018. Socio-demographic and microbiological data were obtained from the National Public Health surveillance system, through a specialized notification sheet. The relationship of device-associated infections with several outcomes including birth weight, microorganisms, and mortality was evaluated using OR CI95%, using the logistic regression model. Data processing was performed using the statistical program STATA 16. Results: 226 device-associated infections were reported. The rate of infection with central line-associated bloodstream infections was 2.62 per 1000 days of device use and 2.32 per 1000 days for ventilator-associated pneumonia. This was higher in neonates under 1000 g; 4.59 and 4.10, respectively. 43.4% of the infections were due to gram-negative bacteria and 42.3% were due to gram-positive bacteria. Time from hospitalization to diagnosis of all device-associated infections had a median of 14 days. When compared by weight, infants with a weight lower than 1000 g had a greater chance of death (OR 3.61; 95% CI 1.53–8.49, p = 0.03). Infection by gram-negative bacteria was associated with a greater chance of dying (OR 3.06 CI 95 1.33–7.06, p = 0.008). Conclusions: These results highlight the need to maintain epidemiological surveillance processes in neonatal intensive care units, especially when medical devices are used.

Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP). We determined the production of intestinal cytokines, the lymphocyte populations in both the colon and the spleen, and the genetic expression of markers of intestinal epithelial integrity. We observed a general downregulation of the intestinal immune response in mice receiving FMT-P. We found significantly lower intestinal production of the cytokines IL-6, TNF, IFN-γ, MCP-1, IL-10, and IL-12 in the FMT-P. Furthermore, a significant decrease in the proportion of CD3+, CD4+, and Foxp3+ T regulatory cells (Treg) was observed in both, the colon and spleen with FMT-P in contrast to FMT-NP. We also found that in FMT-P mice there was a significant decrease in tjp1 expression in all three regions of the small intestine; ocln in the ileum; reg3γ in the duodenum and relmβ in both the duodenum and ileum. We also found an increase in colonic mucus layer thickness in mice colonized with FMT-P in contrast with FMT-NP. Finally, our results suggest that gut protozoa, such as Blastocystis hominis, Entamoeba coli, Endolimax nana, Entamoeba histolytica/E. dispar, Iodamoeba bütschlii, and Chilomastix mesnili consortia affect the immunoinflammatory state and induce functional changes in the intestine via the gut microbiota. Likewise, it allows us to establish an FMT model in germ-free mice as a viable alternative to explore the effects that exposure to intestinal parasites could have on the immune response in humans.

The membrane flickering of human fetal red blood cells (RBCs) affected by gestational diabetes mellitus (GDM) was studied with dual time resolved membrane fluctuation spectroscopy (D-TRMFS). This new technique is a modified version of the dual optical tweezers method that has been adapted to measure the mechanical properties of RBCs at two distant membrane points simultaneously. The micro-rheological parameters were obtained from direct membrane flickering measurements, followed by Fourier decomposition and cell membrane model adjustment. Our results show a significant decrease of 6.01 ± 1.19 nm in membrane fluctuations amplitude in healthy fetal, compared with healthy adult RBCs, meanwhile the amplitude in GDM cells increased 3.22 ± 1.10 nm compared with healthy fetal RBCs. Between GDM and healthy fetal RBCs, there are significant differences, especially in the bending modulus. Considering the mean of the two membrane points measured, the tension for GDM RBCs increased by 6.431 ± 3.57 (10−7 [N/m]) compared with healthy fetal RBCs, meanwhile, the bending was increased by 2.483 ± 0.58 (10−19 [J]) in GDM compared with healthy fetal RBCs. These results showed significant increment of 1.23 ± 0.07-fold and 3.29 ± 0.36-fold in tension and bending modulus in GDM, respectively. The strong impact of GDM on bending modulus could be associated with oxidative stress and lipid peroxidation, previously reported in fetal plasma of GDM cases.

Abstract Precision medicine offers remarkable potential for the treatment of cancer, but is largely focused on tumors that harbor actionable mutations. Gene expression signatures can expand the scope of precision medicine by predicting response to traditional (cytotoxic) chemotherapy agents without relying on changes in mutational status. We present a new signature extraction method, inspired by the principle of convergent phenotypes, which states that tumors with disparate genetic backgrounds may evolve similar phenotypes independently. This evolutionary-informed method can be utilized to produce consensus signatures predictive of response to over 200 chemotherapeutic drugs found in the Genomics of Drug Sensitivity in Cancer (GDSC) Database. Here, we demonstrate its use by extracting the Cisplatin Response Signature (CisSig). We show that this signature can predict cisplatin response within carcinoma-based cell lines from the GDSC database, and expression of the signatures aligns with clinical trends seen in independent datasets of tumor samples from The Cancer Genome Atlas (TCGA) and Total Cancer Care (TCC) database. Finally, we demonstrate preliminary validation of CisSig for use in muscle-invasive bladder cancer, predicting overall survival in a small cohort of patients who undergo cisplatin-containing chemotherapy. This methodology can be used to produce robust signatures that, with further clinical validation, may be used for the prediction of traditional chemotherapeutic response, dramatically increasing the reach of personalized medicine in cancer.

Introduction. The birth of premature babies is a public health problem with a high impact on infant morbidity and mortality. About 40% of mortality in children under five years occurs in the first month of life. Objective. To identify the association between maternal sociodemographic factors, premature birth, and mortality in newborns under 37 weeks in Santiago de Cali, 2017-2019. Materials and methods. We conducted a descriptive, cross-sectional study. We evaluated the records of Cali’s Municipal Public Health Office. We calculated the crude and adjusted odd ratios and confidence intervals (95%) using the logistic regression model, data processing in Stata 16, and georeferencing the cases in the QGIS software. Results. From 2017 to 2019, premature babies in Cali corresponded to 11% of births. Poor prenatal care increased 3.13 times the risk of being born before 32 weeks (adjusted OR = 3.13; 95% CI = 2.75 - 3.56) and 1.27 times among mothers from outside the city (adjusted OR = 1.27; 95% CI = 1.15-1.41). Mortality was 4.29 per 1,000 live births. The mortality risk in newborns weighing less than 1,000 g increased 3.42 times (OR = 3.42; 95% CI = 2.85-4.12), delivery by cesarean section in 1.46 (OR = 1.46; CI 95% = 1.14-1.87) and an Apgar score – five minutes after birth– lower than seven in 1.55 times (OR = 1.55; CI 95% = 1.23-1.96). Conclusions. We found that less than three prenatal controls, mothers living outside Cali, afro-ethnicity, and cesarean birth were associated with prematurity of less than 32 weeks. We obtained higher mortality in newborns weighing less than 1,000 g.

Abstract Participation in cancer research trials by minority populations is imperative in reducing disparities in clinical outcomes. Even with increased awareness of the importance of minority patient inclusion in clinical research to improve cancer care and survival, significant barriers persist in accruing and retaining minority patients into clinical trials. This study sought to identify and address barriers to minority accrual to a minimal risk clinical research study in real‐time.

Abstract Using a metagenomic sequencing approach, we described and compared the diversity and dynamics of the oropharyngeal and fecal eukaryotic virome of nine asymptomatic children in a semi-rural community setting located in the State of Morelos, Mexico. Ninety oropharyngeal swabs and 97 fecal samples were collected starting 2 weeks after birth and monthly thereafter until 12 months of age. In both niches, more than 95% of the total sequence reads were represented by viruses that replicate either in humans or in plants. Regarding human viruses, three families were most abundant and frequent in the oropharynx: Herpesviridae, Picornaviridae, and Reoviridae; in fecal samples, four virus families predominated: Caliciviridae, Picornaviridae, Reoviridae, and Anelloviridae. Both niches showed a high abundance of plant viruses of the family Virgaviridae. Differences in the frequency and abundance of sequence reads and diversity of virus species were observed in both niches and throughout the year of study, with some viruses already present in the first months of life. Our results suggest that the children’s virome is dynamic and likely shaped by the environment, feeding, and age. Moreover, composition analysis suggests that the virome composition is mostly individual. Whether this constant exposition to different viruses has a long-term impact on children’s health or development remains to be studied.

Helicobacter pylori have coevolved with mankind since its origins, adapting to different human groups. In America, H. pylori has evolved into several subpopulations. We analysed the genome of 154 Colombian strains along with 1,091 strains from worldwide populations to discern the ancestry and adaption to Colombian people. Population structure and ancestry was inferred with FineStructure and ChromoPainter. Phylogenetic relationship and the relative effect of recombination were analysing the core SNPs. Also, a Fst index was calculated to identify the gene variants with the strongest fixation in the Colombian subpopulations compared to their parent population hspSWEurope. FineStructure allowed the identification of two Colombian subpopulations, the previously described hspSWEuropeColombia and a novel subpopulation named hspColombia, that included three subgroups following their geographic origin. Colombian subpopulations represent an admixture of European, African and Indigenous ancestry; although some genomes showed a high proportion of self identity, suggesting an advanced adaption to these mestizo Colombian groups. We found that recombination is more important that punctual mutations in H. pylori genome diversity, 13.9 more important in hspSWEurope, 12.5 in hspSWEColombia and 10.5 in hspColombia, reflecting the divergence of these subpopulations. Fst analysis identified 82 SNPs fixed in 26 genes of the hspColombia subpopulation that encode for outer membrane and central metabolism proteins. Strongest fixation indexes were identified in genes encoding HofC, HopE, FrpB-4 and Sialidase A. These findings demonstrate that H. pylori has evolved in Colombia to give rise to subpopulations with a self identity ancestry, reflected in allele changes on genes encoding for outer membrane proteins.

ABSTRACT Studies on the role of the oral microbiome in SARS-CoV-2 infection and severity of the disease are limited. We aimed to characterize the bacterial communities present in the saliva of patients with varied COVID-19 severity to learn if there are differences in the characteristics of the microbiome among the clinical groups. We included 31 asymptomatic subjects with no previous COVID-19 infection or vaccination; 176 patients with mild respiratory symptoms, positive or negative for SARS-CoV-2 infection; 57 patients that required hospitalization because of severe COVID-19 with oxygen saturation below 92%, and 18 fatal cases of COVID-19. Saliva samples collected before any treatment were tested for SARS-CoV-2 by PCR. Oral microbiota in saliva was studied by amplification and sequencing of the V1-V3 variable regions of 16S gene using an Illumina MiSeq platform. We found significant changes in diversity, composition, and networking in saliva microbiota of patients with COVID-19, as well as patterns associated with severity of disease. The presence or abundance of several commensal species and opportunistic pathogens were associated with each clinical stage. Patterns of networking were also found associated with severity of disease: a highly regulated bacterial community (normonetting) was found in healthy people whereas poorly regulated populations (disnetting) were characteristic of severe cases. Characterization of microbiota in saliva may offer important clues in the pathogenesis of COVID-19 and may also identify potential markers for prognosis in the severity of the disease. IMPORTANCE SARS-CoV-2 infection is the most severe pandemic of humankind in the last hundred years. The outcome of the infection ranges from asymptomatic or mild to severe and even fatal cases, but reasons for this remain unknown. Microbes normally colonizing the respiratory tract form communities that may mitigate the transmission, symptoms, and severity of viral infections, but very little is known on the role of these microbial communities in the severity of COVID-19. We aimed to characterize the bacterial communities in saliva of patients with different severity of COVID-19 disease, from mild to fatal cases. Our results revealed clear differences in the composition and in the nature of interactions (networking) of the bacterial species present in the different clinical groups and show community-patterns associated with disease severity. Characterization of the microbial communities in saliva may offer important clues to learn ways COVID-19 patients may suffer from different disease severities.

ABSTRACT Patients with 2019 coronavirus disease (COVID-19) exhibit a broad spectrum of clinical presentations. A person’s antimicrobial antibody profile, as partially shaped by past infection or vaccination, can reflect the immune system health that is critical to control and resolve the infection. We performed an explorative immunoproteomics study using microbial protein arrays displaying 318 full-length antigens from 77 viruses and 3 bacteria. We compared antimicrobial antibody profiles between 135 patients with mild COVID-19 disease and 215 patients with severe disease in 3 independent cohorts from Mexico and Italy. Severe disease patients were older with higher prevalence of comorbidities. We confirmed that severe disease patients elicited a stronger anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) response. We showed that antibodies against HCoV-229E and HcoV-NL63 but not against HcoV-HKU1 and HcoV-OC43 were also higher in those who had severe disease. We revealed that for a set of IgG and IgA antibodies targeting coronaviruses, herpesviruses, and other respiratory viruses, a subgroup of patients with the highest reactivity levels had a greater incidence of severe disease compared to those with mild disease across all three cohorts. On the contrary, fewer antibodies showed consistent greater prevalence in mild disease in all 3 cohorts. IMPORTANCE The clinical presentations of COVID-19 range from asymptomatic to critical illness that may lead to intensive care or even death. The health of the immune system, as partially shaped by past infections or vaccinations, is critical to control and resolve the infection. Using an innovative protein array platform, we surveyed antibodies against hundreds of full-length microbial antigens from 80 different viruses and bacteria in COVID-19 patients from different geographic regions with mild or severe disease. We not only confirmed the association of severe COVID-19 disease with higher reactivity of antibody responses to SARS-CoV-2 but also uncovered known and novel associations with antibody responses against herpesviruses and other respiratory viruses. Our study represents a significant step forward in understanding the factors contributing to COVID-19 disease severity. We also demonstrate the power of comprehensive antimicrobial antibody profiling in deciphering risk factors for severe COVID-19. We anticipate that our approach will have broad applications in infectious diseases.

El ataque cerebrovascular recurrente (ACV) es una complicación rara del síndrome del opérculo torácico arterial. Presentamos un paciente de 24 años con isquemia del miembro superior derecho y ACV recurrente en territorio vertebro basilar secundario a estenosis y aneurisma de la arteria subclavia, causado por sinostosis de la primera y segunda costillas torácicas. El paciente fue tratado quirúrgicamente con costocondrectomía y escalenectomía bilateral, resección de aneurisma de la arteria subclavia derecha y anastomosis primaria. Se analizó el caso y se revisó la literatura pertinente sobre ACV y síndrome de opérculo torácico arterial.

Mitochondrial dGTP is mostly bound to an accessory subunit of complex I of the mitochondrial respiratory chain, which may reveal a mechanism linking mitochondrial dNTP availability and oxidative metabolism.

Los sobrevivientes de la reanimación cardiopulmonar posterior a un paro cardiaco pueden tener un amplio rango de desenlaces y van desde recuperación neurológica completa, estado de vigilia sin respuesta, compromiso cognoscitivo diverso o la muerte. La lesión del tejido cerebral se presenta inmediatamente después del paro cardíaco, durante la reanimación y al retornar la circulación espontánea. La severidad y duración de la noxa isquémica determinarán el devenir neurológico. El examen clínico es el punto de partida en el abordaje multimodal del neuropronóstico. Se debe complementar con electroencefalograma, potenciales evocados somatosensoriales, neuroimágenes y biomar-cadores séricos. Entre un 10 a 15% de los pacientes con lesión cerebral posterior al paro cardiaco evolucionan hacia muerte por criterios neurológicos y son potenciales candidatos a la donación de órganos. Un retiro temprano de las terapias de sostenimiento de vida puede malograr la posibilidad de un potencial donante de órganos. Se puede estimar de manera temprana qué pacientes tienen mayor riesgo de evolucionar a muerte por criterios neurológicos. El neurólogo tiene un papel protagónico en el manejo de pacientes con lesión cerebral post paro cardiaco y sus decisiones tienen implicaciones éticas y legales.

BackgroundMental health among university students is a public health problem in Chile, understanding that this population is susceptible to mental disorders.ObjectiveThe present study aimed to determine the prevalence and variables influencing depression, anxiety, and stress in Chilean university students.MethodA representative sample (n = 1,062) of Chilean university students and a cross-sectional study design were used. Bivariate analysis and multiple logistic regression were performed to identify risk factors associated with symptomatology. They were analyzed using descriptive statistics. A questionnaire with sociodemographic variables was applied in November 2022, in addition to the depression anxiety stress scale (DASS-21), instruments with excellent reliability in this population (α = 0.955; ω = 0.956). On the other hand, the Questionnaire of Problematic Alcohol and Drug Consumption (DEP-ADO) was applied. A descriptive analysis was performed, followed by bivariate analysis and multiple logistic regression using SPSS version 25. The variables showed a value of p

Abstract Introduction Several systemic therapies have demonstrated a survival advantage in metastatic castration resistant prostate cancer (mCRPC). Access to these medications varies significantly worldwide. In Australia until recently, patients must have received docetaxel first, unless unsuitable for chemotherapy, despite no evidence suggesting superiority over androgen receptor signalling inhibitors (ARSIs). Our study investigated real‐world systemic treatment patterns in Australian patients with mCRPC. Methods The electronic CRPC Australian Database (ePAD) was interrogated to identify mCRPC patients. Clinicopathological features, treatment and outcome data, stratified by first‐line systemic therapies, were extracted. Comparisons between groups utilised Kruskal–Wallis tests and Chi‐Square analyses. Time‐to‐event data were calculated using Kaplan–Meier methods and groups compared using log‐rank tests. Factors influencing overall survival (OS) and time to treatment failure (TTF) were analysed through Cox proportional hazards regression models. Results We identified 578 patients who received first‐line systemic therapy for mCRPC. Enzalutamide (ENZ) was most commonly prescribed (n = 240, 41%), followed by docetaxel (DOC, n = 164, 28%) and abiraterone (AA, n = 100, 17%). Patients receiving ENZ or AA were older (79, 78.5 years respectively) compared with DOC (71 years, p = 0.001) and less likely to have ECOG performance status 0 (45%, 44%, 59% in ENZ, AA and DOC groups respectively p 12 months was independently associated with longer TTF (HR 0.67, p

CagY is the largest and most complex protein from Helicobacter pylori’s (Hp) type IV secretion system (T4SS), playing a critical role in the modulation of gastric inflammation and risk for gastric cancer. CagY spans from the inner to the outer membrane, forming a channel through which Hp molecules are injected into human gastric cells. Yet, a tridimensional structure has been reported for only short segments of the protein. This intricate protein was modeled using different approaches, including homology modeling, ab initio, and deep learning techniques. The challengingly long middle repeat region (MRR) was modeled using deep learning and optimized using equilibrium molecular dynamics. The previously modeled segments were assembled into a 1595 aa chain and a 14-chain CagY multimer structure was assembled by structural alignment. The final structure correlated with published structures and allowed to show how the multimer may form the T4SS channel through which CagA and other molecules are translocated to gastric cells. The model confirmed that MRR, the most polymorphic and complex region of CagY, presents numerous cysteine residues forming disulfide bonds that stabilize the protein and suggest this domain may function as a contractile region playing an essential role in the modulating activity of CagY on tissue inflammation.

Pyoderma gangrenosum (PG) is an uncommon, idiopathic, neutrophilic dermatosis characterised by large necrotic ulcers. Occasionally, patients develop atypical presentations, including pustular, bullous, and vegetative lesions. Bullous pyoderma gangrenosum (BPG) is considered an extremely rare form. We describe a case of BPG in a 76-year-old man, with active oncological history, including a recent diagnosis of hairy cell leukemia. Diagnosis of PG was delayed because of atypical clinical presentation that mimicked necrotising fasciitis. The patient was treated with diverse intravenous antibiotics and several surgical procedures. The suspicion of neutrophilic dermatosis arose from the histopathological studies. In the setting of mandatory clinico-pathological correlation, the aim of this report is to point out the morphological characteristics that allow recognition of this uncommon variant of pyoderma gangrenosum.

BackgroundAfter exposure to SARS-CoV-2 and/or vaccination there is an increase in serum antibody titers followed by a non-linear waning. Our aim was to find out if this waning of antibody titers would fit to a mathematical model.MethodsWe analyzed anti-RBD (receptor binding domain) IgG antibody titers and the breakthrough infections over a ten-month period following the second dose of the mRNA BNT162b2 (Pfizer-BioNtech.) vaccine, in a cohort of 54 health-care workers (HCWs) who were either never infected with SARS-CoV-2 (naïve, nHCW group, n=27) or previously infected with the virus (experienced, eHCW group, n=27). Two mathematical models, exponential and power law, were used to quantify antibody waning kinetics, and we compared the relative quality of the goodness of fit to the data between both models was compared using the Akaik Information Criterion.ResultsWe found that the waning slopes were significantly more pronounced for the naïve when compared to the experienced HCWs in exponential (p-value: 1.801E-9) and power law (p-value: 9.399E-13) models. The waning of anti-RBD IgG antibody levels fitted significantly to both exponential (average-R2: 0.957 for nHCW and 0.954 for eHCW) and power law (average-R2: 0.991 for nHCW and 0.988 for eHCW) models, with a better fit to the power law model. In the nHCW group, titers would descend below an arbitrary 1000-units threshold at a median of 210.6 days (IQ range: 74.2). For the eHCW group, the same risk threshold would be reached at 440.0 days (IQ range: 135.2) post-vaccination.ConclusionTwo parsimonious models can explain the anti-RBD IgG antibody titer waning after vaccination. Regardless of the model used, eHCWs have lower waning slopes and longer persistence of antibody titers than nHCWs. Consequently, personalized vaccination booster schedules should be implemented according to the individual persistence of antibody levels.

Hungatella hathewayi has been observed to be a member of the gut microbiome. Unfortunately, little is known about this organism in spite of being associated with human fatalities; it is important to understand virulence mechanisms and epidemiological prospective to cause disease. In this study, a patient with chronic neurologic symptoms presented to the clinic with subsequent isolation of a strain with phenotypic characteristics suggestive of Clostridium difficile. However, whole-genome sequence found the organism to be H. hathewayi. Analysis including publicly available Hungatella genomes found substantial genomic differences as compared to the type strain, indicating this isolate was not C. difficile. We examined the whole-genome of Hungatella species and related genera, using comparative genomics to fully examine species identification and toxin production. Orthogonal phylogenetic using the 16S rRNA gene and entire genome analyses that included genome distance analyses using Genome-to-Genome Distance (GGDC), Average Nucleotide Identity (ANI), and a pan-genome analysis with inclusion of available public genomes determined the speciation to be Hungatella. Two clearly differentiated groups were identified, one including a reference H. hathewayi genome (strain DSM-13,479) and a second group that was determined to be H. effluvii, which included our clinical isolate. Also, some genomes reported as H. hathewayi were found to belong to other genera, including Clostridium and Faecalicatena. We show that the Hungatella species have an open pan-genome reflecting high genomic diversity. This study highlights the importance of correctly assigning taxonomic identification, particularly in disease-associated strains, to better understand virulence and therapeutic options.

BackgroundThe Collective Efficacy Scale Short-Form (CES-SF) is a short and reliable instrument that assesses collective efficacy in schools at a group level. Previous research has shown a two-factor structure considering the perception of the group competence about their teaching capabilities and task analysis that refers to the opportunities inherent to a specific task. However, there is no conclusive evidence that collective efficacy corresponds to a two-factor model or single-factor structure.MethodsA cross-sectional research was conducted on a 693 sample of teachers (Mage = 39.4; SD = 11.8) from schools in the 16 regions of Chile. They were assessed using the CES-SF, Personal Well-being Index, Social Well-Being Scale, and satisfaction with the school. Exploratory and confirmatory factor analyses were used to assess the construct validity of the CES-SF.ResultsThe CES-SF showed mixed results about its construct validity. Best fit has been found to retain two new factors (opportunities and challenges for collective efficacy) with eight items each, yielding a McDonald’s ω of 0.803. Convergent validity was also established.ConclusionThe psychometric results suggest that a two-factor structure for the CES-SF is a valid and reliable measure for this construct for Chilean teachers. However, collective efficacy might not strongly relate to subjective wellbeing but to school-context variables.

The genome of Mycobacterium tuberculosis (Mtb) harbors the genetic machinery for assembly of the Fimbrial low-molecular-weight protein (Flp) type IV pilus. Presumably, the Flp pilus is essential for pathogenesis. However, it remains unclear whether the pili genes are transcribed in culture or during infection of host cells. This study aimed to shed light on the expression of the Flp pili-assembly genes (tadZ, tadA, tadB, tadC, flp, tadE, and tadF) in Mtb growing under different growth conditions (exponential phase, stationary phase, and dormancy NRP1 and NRP2 phases induced by hypoxia), during biofilm formation, and in contact with macrophages and alveolar epithelial cells. We found that expression of tad/flp genes was significantly higher in the stationary phase than in exponential or NRP1 or NRP2 phases suggesting that the bacteria do not require type IV pili during dormancy. Elevated gene expression levels were recorded when the bacilli were in contact for 4 h with macrophages or epithelial cells, compared to mycobacteria propagated alone in the cultured medium. An antibody raised against a 12-mer peptide derived from the Flp pilin subunit detected the presence of Flp pili on intra- and extracellular bacteria infecting eukaryotic cells. Altogether, these are compelling data showing that the Flp pili genes are expressed during the interaction of Mtb with host cells and highlight a role for Flp pili in colonization and invasion of the host, subsequently promoting bacterial survival during dormancy.

This research assessed oral health behaviors changes in urban families with young children during the stay-at-home period of the COVID-19 pandemic (Nov 2020–August 2021). Survey data on oral health behaviors were collected in homes at three points before COVID-19, and via phone during COVID-19. A subset of parents and key informants from clinics and social service agencies completed in-depth interviews via video/phone. Of the 387 parents invited, 254 completed surveys in English or Spanish (65.6%) during COVID-19. Fifteen key informant interviews (25 participants) and 21 family interviews were conducted. The mean child age was 4.3 years. Children identified as mainly Hispanic (57%) and Black race (38%). Parents reported increased child tooth brushing frequency during the pandemic. Family interviews highlighted changes in family routines that impacted oral health behaviors and eating patterns, suggesting less optimal brushing and nutrition. This was linked to changed home routines and social presentability. Key informants described major disruptions in oral health services, family fear, and stress. In conclusion, the stay-at-home period of the COVID-19 pandemic was a time of extreme routine change and stress for families. Oral health interventions that target family routines and social presentability are important for families during times of extreme crisis.

Mitochondrial DNA (mtDNA) depletion/deletions syndromes (MDDS) encompass a clinically and etiologically heterogenous group of mitochondrial disorders caused by impaired mtDNA maintenance. Among the most frequent causes of MDDS are defects in nucleoside/nucleotide metabolism, which is critical for synthesis and homeostasis of the deoxynucleoside triphosphate (dNTP) substrates of mtDNA replication. A central enzyme for generating dNTPs is ribonucleotide reductase, a critical mediator of de novo nucleotide synthesis composed of catalytic RRM1 subunits in complex with RRM2 or p53R2. Here, we report 5 probands from 4 families who presented with ptosis and ophthalmoplegia as well as other clinical manifestations and multiple mtDNA deletions in muscle. We identified 3 RRM1 loss-of-function variants, including a dominant catalytic site variant (NP_001024.1: p.N427K) and 2 homozygous recessive variants at p.R381, which has evolutionarily conserved interactions with the specificity site. Atomistic molecular dynamics simulations indicate mechanisms by which RRM1 variants affect protein structure. Cultured primary skin fibroblasts of probands manifested mtDNA depletion under cycling conditions, indicating impaired de novo nucleotide synthesis. Fibroblasts also exhibited aberrant nucleoside diphosphate and dNTP pools and mtDNA ribonucleotide incorporation. Our data reveal that primary RRM1 deficiency and, by extension, impaired de novo nucleotide synthesis are causes of MDDS.

This study analyzed the mediating role that implicit theories of intelligence and academic self-efficacy may play in the relationship between psychopathology and mathematical performance. The sample consisted of 838 students from first and second year of high school. A numerical calculation test was applied, followed by psychopathology self-report scales, implicit theories of intelligence, and academic self-efficacy. Serial multiple mediation models were tested. The results showed a complete mediation of the effect of psychopathology on mathematical performance through implicit theories of intelligence and academic self-efficacy. The effect of entity theories of intelligence on mathematical performance was both direct and through academic self-efficacy, whereas the effect of incremental theories of intelligence was only through academic self-efficacy. Identifying the variables that mediate the relationship in question is crucial to develop targeted interventions to prevent the development of a vicious circle between psychopathology and poor school performance.

AbstractBackground COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood.Methods We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells.Results Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2).Conclusions The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy.Key messagesCritically ill COVID-19 patients show emergency myelopoiesis.HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets.HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

Objective: To determine the efficacy and safety of intermittent docetaxel chemotherapy guided by circulating methylated glutathione S-transferase Pi-1 ( mGSTP1 ) in men with metastatic castration-resistant prostate cancer (CRPC). Patients and Methods: GUIDE (NCT04918810) is a randomised, two-arm, non-comparative phase-2 trial recruiting 120 patients at six Australian centres. Patients with Prostate Cancer Working Group-3 defined metastatic CRPC who are commencing docetaxel 75 mg/m 2 q3w will be pre-screened for detectable mGSTP1 at baseline ± following two cycles of treatment. Those with detectable plasma mGSTP1 at baseline that becomes undetectable after two cycles of chemotherapy will be eligible for GUIDE. Prior to Cycle 4 of docetaxel, these patients are randomised 2:1 to one of two treatment arms: Arm A (cease docetaxel and reinstitute if mGSTP1 becomes detectable) or Arm B (continue docetaxel 75 mg/m 2 q3w in accordance with clinician’s usual practice). The primary endpoint is radiographic progression-free survival. Secondary endpoints include time on treatment holidays, safety, patient-reported outcomes, overall survival, health resource use, and cost associated with treatment. Enrolment commenced November 2021. Results and Conclusion: The results of this trial will generate data on the clinical utility of mGSTP1 as a novel biomarker to guide treatment de-escalation in metastatic CRPC.

Clostridioides difficile is a global public health problem, which is a primary cause of antibiotic-associated diarrhea in humans. The emergence of hypervirulent and antibiotic-resistant strains is associated with the increased incidence and severity of the disease. There are limited studies on genomic characterization of C. difficile in Latin America. We aimed to learn about the molecular epidemiology and antimicrobial resistance in C. difficile strains from adults and children in hospitals of México. We studied 94 C. difficile isolates from seven hospitals in Mexico City from 2014 to 2018. Whole-genome sequencing (WGS) was used to determine the genotype and examine the toxigenic profiles. Susceptibility to antibiotics was determined by E-test. Multilocus sequence typing (MLST) was used to determine allelic profiles. Results identified 20 different sequence types (ST) in the 94 isolates, mostly clade 2 and clade 1. ST1 was predominant in isolates from adult and children. Toxigenic strains comprised 87.2% of the isolates that were combinations of tcdAB and cdtAB (tcdA+/tcdB+/cdtA+/cdtB+, followed by tcdA+/tcdB+/cdtA−/cdtB−, tcdA−/tcdB+/cdtA−/ cdtB−, and tcdA−/tcdB−/cdtA+/cdtB+). Toxin profiles were more diverse in isolates from children. All 94 isolates were susceptible to metronidazole and vancomycin, whereas a considerable number of isolates were resistant to clindamycin, fluroquinolones, rifampicin, meropenem, and linezolid. Multidrug-resistant isolates (≥3 antibiotics) comprised 65% of the isolates. The correlation between resistant genotypes and phenotypes was evaluated by the kappa test. Mutations in rpoB and rpoC showed moderate concordance with resistance to rifampicin and mutations in fusA substantial concordance with fusidic acid resistance. cfrE, a gene recently described in one Mexican isolate, was present in 65% of strains linezolid resistant, all ST1 organisms. WGS is a powerful tool to genotype and characterize virulence and antibiotic susceptibility patterns.

Purpose: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents 90% of all chronic prostatitis cases and may occur after radiation therapy (RT) for localized prostate cancer. Medical therapy is effective in approximately 50% of cases, with no therapy demonstrating consistent efficacy in refractory cases. Prostatic artery embolization (PAE) is effective in men with lower urinary tract symptoms and benign prostatic hyperplasia. We report clinical improvement after PAE in a case series of men with CP/CPPS after RT. Methods and Materials: Nine men (median age 72 years; range, 61-83 years) with CP/CPPS after RT for prostate cancer underwent PAE. Baseline International Prostate Symptom Score was recorded in 5 patients (median 23; range, 4-26), Chronic Prostatitis Symptom Index score in 6 patients (median 22.5; range, 6-34), and quality of life (QoL) score in 8 patients (median 5; range, 2-6). Median baseline prostate volume was 49 cm3 (range, 22-123 cm3). Patients were followed up at 6 and 12 weeks with QoL, International Prostate Symptom Score, and/or Chronic Prostatitis Symptom Index score and magnetic resonance imaging. Results: Technical success (ie, bilateral embolization) was achieved in 78% (n = 7) of patients with the other 2 patients having undergone unilateral embolization with no major complications. Clinical success was seen in 89% (n = 8) of patients and QoL improved in 78% (n = 7) during the follow-up period. Conclusion: CP/CPPS after RT for localized prostate cancer is a highly morbid condition, with medical therapy successful in only 50% of cases. PAE may be a successful therapy for medically recalcitrant CP/CPPS, and further studies are necessary to understand the best patient selection and scenario for PAE in the setting of CP/CPPS.

Abstract Plant viruses have been reported to be common in the gut of human adults, presumably as result of food ingestion. In this work, we report that plant viruses can also be found frequently in the gut and oropharynx of children during their first year of life, even when they are exclusively breast-fed. Fecal and oropharynx samples were collected monthly, from birth to 1 year of age, from three apparently healthy children in a semi-rural community and analyzed by next generation sequencing. In 100% of the fecal samples and 65% of the oropharynx samples at least one plant virus was identified. Tobamoviruses in the Virgaviridae family were by far the most frequently detected, with tropical soda apple mosaic virus, pepper mild mottle virus, and opuntia tobamovirus 2 being the most common species. Seventeen complete virus genomes could be assembled, and phylogenetic analyses showed a large diversity of virus strains circulating in the population. These results suggest that children are continuously exposed to an extensive and highly diverse collection of tobamoviruses. Whether the common presence of plant viruses at an early age influences the infant’s immune system, either directly or through interaction with other members of the microbiota, remains to be investigated.

Abstract Background The therapeutic landscape in medical oncology continues to expand significantly. Newer therapies, especially immunotherapy, offer the hope of profound and durable responses with more tolerable side effect profiles. Integrating this information into the decision making process is challenging for patients and oncologists. Systemic anticancer treatment within the last thirty days of life is a key quality of care indicator and is one parameter used in the assessment of aggressiveness of care. Methods A retrospective review of medical records of all patients previously treated at Goulburn Valley Health oncology department who died between 1 January 2015 and 30 June 2018 was conducted. Information collected related to patient demographics, diagnosis, treatment, and hospital care within the last 30 days of life. These results were presented to the cancer services meeting and a quality improvement intervention program was instituted. A second retrospective review of medical records of all patients who died between 1 July 2018 and 31 December 2018 was conducted in order to measure the effect of this intervention. Results The initial audit period comprised 440 patients. 120 patients (27%) received treatment within the last 30 days of life. The re-audit period comprised 75 patients. 19 patients (25%) received treatment within the last 30 days of life. Treatment rates of chemotherapy reduced after the intervention in contrast to treatment rates of immunotherapy which increased. A separate analysis calculated the rate of mortality within 30 days of chemotherapy from the total number of patients who received chemotherapy was initially 8% and 2% in the re-audit period. Treatment within the last 30 days of life was associated with higher use of aggressive care such as emergency department presentation, hospitalisation, ICU admission and late hospice referral. Palliative care referral rates improved after the intervention. Conclusion This audit demonstrated that a quality improvement intervention can impact quality of care indicators with reductions in the use of chemotherapy within the last 30 days of life. However, immunotherapy use increased which may be explained by increased access and a better risk benefit balance.

ABSTRACT We recently carried out a metagenomic study to determine the fecal virome of infants during their first year of life in a semirural community in Mexico. A total of 97 stool samples from nine children were collected starting 2 weeks after birth and monthly thereafter until 12 months of age. In this work, we describe the prevalence and incidence of caliciviruses in this birth cohort. We found that 54 (56%) and 24 (25%) of the samples were positive for norovirus and sapovirus sequence reads detected by next-generation sequencing, respectively. Potential infections were arbitrarily considered when at least 20% of the complete virus genome was determined. Considering only these samples, there were 3 cases per child/year for norovirus and 0.33 cases per child/year for sapovirus. All nine children had sequence reads related to norovirus in at least 2 and up to 10 samples, and 8 children excreted sapovirus sequence reads in 1 and up to 5 samples during the study. The virus in 35 samples could be genotyped. The results showed a high diversity of both norovirus (GI.3[P13], GI.5, GII.4, GII.4[P16], GII.7[P7], and GII.17[P17]) and sapovirus (GI.1, GI.7, and GII.4) in the community. Of interest, despite the frequent detection of caliciviruses in the stools, all children remained asymptomatic during the study. Our results clearly show that metagenomic studies in stools may reveal a detailed picture of the prevalence and diversity of gastrointestinal viruses in the human gut during the first year of life. IMPORTANCE Human caliciviruses are important etiological agents of acute gastroenteritis in children under 5 years of age. Several studies have characterized their association with childhood diarrhea and their presence in nondiarrheal stool samples. In this work, we used a next-generation sequencing approach to determine, in a longitudinal study, the fecal virome of infants during their first year of life. Using this method, we found that caliciviruses can be detected significantly more frequently than previously reported, providing a more detailed picture of the prevalence and genetic diversity of these viruses in the human gut during early life.

Horizontal gene transfer (HGT) can allow traits that have evolved in one bacterial species to transfer to another. This has potential to rapidly promote new adaptive trajectories such as zoonotic transfer or antimicrobial resistance. However, for this to occur requires gaps to align in barriers to recombination within a given time frame. Chief among these barriers is the physical separation of species with distinct ecologies in separate niches. Within the genus Campylobacter, there are species with divergent ecologies, from rarely isolated single-host specialists to multihost generalist species that are among the most common global causes of human bacterial gastroenteritis. Here, by characterizing these contrasting ecologies, we can quantify HGT among sympatric and allopatric species in natural populations. Analyzing recipient and donor population ancestry among genomes from 30 Campylobacter species, we show that cohabitation in the same host can lead to a six-fold increase in HGT between species. This accounts for up to 30% of all SNPs within a given species and identifies highly recombinogenic genes with functions including host adaptation and antimicrobial resistance. As described in some animal and plant species, ecological factors are a major evolutionary force for speciation in bacteria and changes to the host landscape can promote partial convergence of distinct species through HGT.

An innovative synthetic route that involves the thermal treatment of selected Ru co−ordination complexes was used to prepare RuO2-based materials with catalytic activity for oxygen reduction (ORR) and oxygen evolution (OER) reactions. Extensive characterization confirmed the presence of Ru metal and RuP3O9 in the materials, with an improved electrocatalytic performance obtained from calcinated [(RuCl2(PPh3)3]. A mechanistic approach for the obtention of such singular blends and for the synergetic contribution of these three species to electrocatalysis is suggested. Catalysts added to carbon−based electrodes were also tested in all−solid and flooded alkaline Zn/air batteries. The former displayed a specific discharge capacity of 10.5 A h g−1 at 250 mA g−1 and a power density of 4.4 kW kg−1 cm−2. Besides, more than 800 discharge/charge cycles were reached in the flooded alkaline Zn/air battery

Background: It has been proposed that transcatheter aortic valve replacement (TAVR) may be an option for patients with cancer and severe aortic stenosis. We assessed the association between previous or active cancer and clinical outcomes in TAVR patients.Methods: We searched four electronic databases from inception to March 05, 2021. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, myocardial infarction, stroke, acute kidney injury, pacemaker implantation, major bleeding, and vascular complications. All meta-analyses were performed using a random-effects model. Relative risks (RRs) and adjusted hazard ratios (aHRs) with their 95% confidence interval (95% CI) were pooled.Results: Thirteen cohort studies involving 255,840 patients were included. The time period for mortality ranged from inpatient to 10 years. Patients with active cancer had a higher risk of all-cause mortality using both crude (RR, 1.46; 95% CI, 1.13–1.88) and adjusted (aHR, 1.79; 95% CI, 1.43–2.25) estimates compared to non-cancer group. In contrast, the risk of cardiovascular mortality (RR, 1.26; 95% CI, 0.58–2.73), myocardial infarction (RR, 0.94; 95% CI, 0.34–2.57), stroke (RR, 0.90; 95% CI, 0.75–1.09), pacemaker implantation (RR, 0.87; 95% CI, 0.50–1.53), acute kidney injury (RR, 0.88; 95% CI, 0.74–1.04), major bleeding (RR, 1.15; 95% CI, 0.80–1.66), and vascular complications (RR, 0.96; 95% CI, 0.79–1.18) was similar between patients with or without cancer.Conclusion: Our review shows that TAVR patients with active cancer had an increased risk of all-cause mortality. No significant association with secondary outcomes was found.

Infection with Helicobacter pylori is one of the most important risk factors for developing gastric cancer (GC). The type IV secretion system (T4SS) encoded in the cag pathogenicity island is the main virulence factor of H. pylori associated with GC. Additionally, other virulence factors have been shown to play a role in the H. pylori virulence, such as vacuolizing cytotoxin (VacA), urease, flagella, and adhesins. Long-chain fatty acids (LCFAs) are signaling molecules that affect the transcription of virulence genes in several pathogenic bacteria such as Salmonella enterica, Vibrio cholerae, Pseudomonas aeruginosa and Mycobacterium tuberculosis. However, the effect of LCFAs on the transcription of H. pylori virulence and regulatory genes remains unknown. Here we analyzed whether the transcription of virulence genes that encode T4SS and cellular envelope components, flagellins, adhesins, toxins, urease, as well as the transcription of different regulatory genes of the H. pylori strain 26695, are altered by the presence of five distinct LCFAs: palmitic, stearic, oleic, linoleic, and linolenic acids. Palmitic and oleic acids up-regulated the transcription of most of the virulence genes tested, including cagL, cagM, flaB, sabA, mraY and vacA, as well as that of the genes encoding the transcriptional regulators NikR, Fur, CheY, ArsR, FlgR, HspR, HsrA, Hup, and CrdR. In contrast, the other LCFAs differentially affected the transcription of the virulence and regulatory genes assessed. Our data show that LCFAs can act as signaling molecules that control the transcription of the H. pylori virulome.

Klebsiella pneumoniae is recognized as a common cause of nosocomial infections and outbreaks causing pneumonia, septicemia, and urinary tract infections. This opportunistic bacterium shows an increasing acquisition of antibiotic-resistance genes, which complicates treatment of infections. Hence, fast reliable strain typing methods are paramount for the study of this opportunistic pathogen’s multi-drug resistance genetic profiles. In this study, thirty-eight strains of K. pneumoniae isolated from the blood of pediatric patients were characterized by whole-genome sequencing and genomic clustering methods. Genes encoding β-lactamase were found in all the bacterial isolates, among which the blaSHV variant was the most prevalent (53%). Moreover, genes encoding virulence factors such as fimbriae, capsule, outer membrane proteins, T4SS and siderophores were investigated. Additionally, a multi-locus sequence typing (MLST) analysis revealed 24 distinct sequence types identified within the isolates, among which the most frequently represented were ST76 (16%) and ST70 (11%). Based on LPS structure, serotypes O1 and O3 were the most prevalent, accounting for approximately 63% of all infections. The virulence capsular types K10, K136, and K2 were present in 16, 13, and 8% of the isolates, respectively. Phylogenomic analysis based on virtual genome fingerprints correlated with the MLST data. The phylogenomic reconstruction also denoted association between strains with a higher abundance of virulence genes and virulent serotypes compared to strains that do not possess these traits. This study highlights the value of whole-genomic sequencing in the surveillance of virulence attributes among clinical K. pneumoniae strains.

Aneurysm clipping requires the proficiency of several skills, yet the traditional way of practicing them has been recently challenged. The use of simulators could be an alternative educational tool. The aim of this data analysis is to provide further evaluation of a reusable low-cost 3D printed training model we developed for aneurysm clipping [1]. The simulator was designed to replicate the bone structure, arteries and targeted aneurysms. Thirty-two neurosurgery residents performed a craniotomy and aneurysm clipping using the model and then filled out a survey. The survey was designed in two parts: a 5-point Likert scale questionnaire and three questions requiring written responses [1]. Two dimensions of the model were evaluated by the questionnaire: the face validity, assessed by 5 questions about the realism of the model, and the content validity, assessed by 6 questions regarding the usefulness of the model during the different steps of the training procedure. The three questions requiring written responses referred to the strengths and weaknesses of the simulator and a global yes/no question as to whether or not they would repeat the experience. Demographic data, experience level and survey responses of the residents were grouped in a dataset [2].A descriptive analysis was performed for each dimension. Then, the groups were compared according to their level of expertise (Junior and Senior groups) with an independent sample t-test. A Confirmatory Factor Analysis (CFA) was estimated, using a Weighted Least Squares Mean Variance adjusted (WLSMV) which works best for the ordinal data [3]. Fitness was calculated using chi-square (χ2) test, Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), and the Root Mean Square Error of Approximation (RMSEA). A non-significant χ2, CFI and TLI greater than 0.90 and RMSEA < 0.08 were considered an acceptable fit [4]. All data analysis was performed using IBM SPSS 23.0 statistical software. Data are reported as mean + standard deviation (SD). A probability p < 0.05 was considered significant.Exploratory Factor Analysis was done to explore the factorial structure of the 11-items scale in the sample, first we performed a principal components analysis. The Kaiser-Meyer-Olkin measure verified the sampling adequacy for the analysis (KMO = 0.784; Bartlett's Test of Sphericity χ2 (55) = 243.44, p < .001), indicating correlation is adequate for factor analysis. Considering Eigen values greater than 1, a two-factor solution explained 73.1% of the variance but left one item in factor 2 (Q 11). The results of this factor analysis are presented in Table 1. Confirmatory Factor Analysis, considering only the 10 items in the first factor (removing question 11 of our model), was performed. This model reached the following fit: χ2 (35) = 38.821, p > .05; CFI = 0.997; TLI = 0.996; RMSEA 0.058, without any error terms to exhibit covariance. Regarding the reliability of the questionnaire, the internal consistency was explored in the 10 items selected in the confirmatory factor analysis with an alpha coefficient (α = 0.941).

The impact of intestinal eukaryotes on the prokaryotic microbiome composition of asymptomatic carriers has not been extensively explored, especially in infants and mothers with multiple parasitic infections. In this work, we studied the relationship between protist and helminth parasite colonization and the intestinal microbiota structure in an asymptomatic population of mother-child binomials from a semirural community in Mexico.