Cardiac manifestations in children with the multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 infection: Systematic review and meta-analysis.

According to the World Health Organisation, as of October 2022, there have been 55,560,329 reported cases of SARS-COV-2 in patients under 19 years old. It is estimated that about 0.06% of these patients may develop MIS-C, representing more than 2 million children worldwide. This systematic review and meta-analysis examined the pooled prevalence of cardiovascular manifestation and cardiac complications in children hospitalised with MIS-C. The PROSPERO register number is CRD42022327212. We included case-report studies, case-control studies, cohort studies, and cross-sectional studies, as well as clinical trials or studies describing cardiac manifestations of MIS-C and its sequelae in a paediatric population. Initially, 285 studies were selected, but there were 154 duplicates, and 81 were excluded because they did not fit the eligibility criteria. Thus, 50 studies were selected for review, and 30 were included in the meta-analysis. A total sample size of 1445 children was included. The combined prevalence of myocarditis or pericarditis was 34.3% (95% CI: 25.0%-44.2%). The combined prevalence for echocardiogram anomalies was 40.8% (95% CI: 30.5%-51.5%), that of Kawasaki disease presentation was 14.8% (95% CI: 7.5%-23.7%), and that of coronary dilation was 15.2% (95% CI: 11.0%-19.8%). The rate of electrocardiogram anomalies was 5.3% (95% CI: 0.8%-12.3%), and the mortality rate was 0.5% (CI 95%: 0%-1.2%). Furthermore, 186 children still had complications at discharge, with a combined prevalence of such long-lasting manifestations of 9.3% (95% CI: 5.6%-13.7%). Studies that assess whether these children will have an increased cardiovascular risk with a greater chance of acute myocardial infarction, arrhythmias, or thrombosis will be essential for healthcare planning.

Dengue virus 3 genotype I (GI) lineage 1 (L1) isolates elicit differential cytopathic effect with syncytium formation in human glioblastoma cells (U251).

BACKGROUND: Dengue virus (DENV) is a Flaviviridae member classified into four antigenically distinct serotypes (DENV 1, 2, 3, and 4) and further subdivided genotypes. DENV3 is subdivided into four or five genotypes, depending on the classification adopted. Despite their high genetic proximity, as revealed by phylogenetic complete polyprotein analysis, DENV3 MG-20 and DENV3 PV_BR showed different neurovirulence in mice models. Our group identified six amino acid mutations in protein E, including the E62K and E123Q, which may affect interactions of hydrophobic clusters on domain II, thus leading to the observed differences in the studied viruses. METHODS: Human glioblastoma cells (U251) derived from a malignant glioblastoma tumor by explant technique were infected by the DENV3 GIL1 isolates DENV3 MG-20 and DENV3 PV_BR and analyzed by plaque assays and titration, optical, immunofluorescence, and transmission electronic microscopy. RESULTS: The two isolates showed different cytopathic effects (CPE) and fusogenic patterns, further confirmed by indirect immunofluorescence. Transmission electron microscopy revealed intense cytopathic effects in DENV3 MG-20 infected U251 cells, displaying endoplasmic reticulum hypertrophy and turgid vesicles with proteins and multiple viruses, distinct from DENV3 PV_BR infected cells. It is hypothesized that the different amino acids in the DENV3 MG-20 isolate are related to an increased membrane fusion ability in viral infection, thus facilitating immune system evasion and increased chances of central nervous system cell infection. CONCLUSION: These results emphasize the biological differences between the isolates, which could be a critical factor in host-virus interaction and severe dengue development. Our study presents comparative results of highly similar isolates with the potential to generate more subsidies for a deeper understanding of the DENV pathogenesis. The neurotropism of the isolate DENV3 MG-20 (belonging to the DENV3 GI L1 genotype) showing infection of nervous system cells (U251) could contribute to understanding neurological dengue disease.

Structure and Functional Properties of Bacterial Communities in Surface Sediments of the Recently Declared Nutrient-Saturated Lake Villarrica in Southern Chile.

Lake Villarrica, one of Chile's main freshwater water bodies, was recently declared a nutrient-saturated lake due to increased phosphorus (P) and nitrogen (N) levels. Although a decontamination plan based on environmental parameters is being established, it does not consider microbial parameters. Here, we conducted high-throughput DNA sequencing and quantitative polymerase chain reaction (qPCR) analyses to reveal the structure and functional properties of bacterial communities in surface sediments collected from sites with contrasting anthropogenic pressures in Lake Villarrica. Alpha diversity revealed an elevated bacterial richness and diversity in the more anthropogenized sediments. The phylum Proteobacteria, Bacteroidetes, Acidobacteria, and Actinobacteria dominated the community. The principal coordinate analysis (PCoA) and redundancy analysis (RDA) showed significant differences in bacterial communities of sampling sites. Predicted functional analysis showed that N cycling functions (e.g., nitrification and denitrification) were significant. The microbial co-occurrence networks analysis suggested Chitinophagaceae, Caldilineaceae, Planctomycetaceae, and Phycisphaerae families as keystone taxa. Bacterial functional genes related to P (phoC, phoD, and phoX) and N (nifH and nosZ) cycling were detected in all samples by qPCR. In addition, an RDA related to N and P cycling revealed that physicochemical properties and functional genes were positively correlated with several nitrite-oxidizing, ammonia-oxidizing, and N-fixing bacterial genera. Finally, denitrifying gene (nosZ) was the most significant factor influencing the topological characteristics of co-occurrence networks and bacterial interactions. Our results represent one of a few approaches to elucidate the structure and role of bacterial communities in Chilean lake sediments, which might be helpful in conservation and decontamination plans.

Ecological risk assessment of glyphosate and its possible effect on bacterial community in surface sediments of a typical shallow Lake, northern China.

Glyphosate is a widely used herbicide worldwide and its prevalent presence in aquatic ecosystems poses a threat to living organisms. This study evaluated potential ecological risk of glyphosate to sediment-dwelling organisms and assessed the probable effect of glyphosate on structure and predicated function of sediment-attached bacterial communities from a large shallow lake in northern China based on 16S rRNA high-throughput sequencing. Results suggested that glyphosate showed a medium to high concentration (up to 8.63 mg/kg) and chronic risk to sediment-dwelling organisms (10% samples exhibiting medium to high risk quotient), especially in sites nearby farmland and residential areas in August. Bacterial community identification based on 16S rRNA sequence indicated some species of dominant phylum Proteobacteria and Campilobacterota (e.g., Steroidobacteraceae, Thiobacillus, Gallionellaceae, Sulfurimonadaceae) were stimulated while some species of dominant phylum Actinobacteriota, Acidobacteriota and Firmicutes (e.g., Nocardioidaceae, Microtrichales, Vicinamibacteraceae, Paenisporosarcina) were inhibited by glyphosate accumulation. The stimulating species were related to sulfur-oxidizing, sulfate-, iron-, or nitrate-reducing bacteria; The inhibiting species were related to plant bacterial endophytes, polyphosphate-accumulating organisms (PAOs) and denitrifers. Correspondingly, promoted bacterial metabolic functions of "sulfite respiration", "nitrogen respiration", "aromatic compound degradation" and "nitrification" but suppressed "cellulolysis", "manganese oxidation", "anoxygenic photoautotrophy S oxidizing" and "nitrate denitrification" were predicated on functional annotation of prokaryotic taxa. Although these results could only partly suggest the impacts of glyphosate on the bacterial communities due to the lack of actual results from control experiments, the identified Steroidobacteraceae could be thought as a bioindicator in the future mechanism study for the ecological effect and bioremediation of glyphosate. This work intends to arise the concern about the depletion of biodiversity and bacterial metabolic functions with contribution of glyphosate in part in eutrophic lakes.

Airborne bacterial community associated with fine particulate matter (PM2.5) under different air quality indices in Temuco city, southern Chile.

Temuco (Chile) is one of the most polluted cities in Chile and Latin America. Although the fine fraction of particulate matter (PM2.5) has been extensively studied and monitored due to its negative impact on public health, its microbiological components remain unknown. We explored, the airborne bacterial community in PM2.5 under good, moderate, alert, pre-emergency and emergency indices of air quality (AQIs) established by the Chilean government. Bacterial community relationship with environmental factors (PM2.5, PM10, carbon monoxide, among others), was also evaluated. Significant differences in PM2.5 bacterial community composition associated with AQIs were revealed, using 16S rRNA target sequences of denaturing gradient gel electrophoresis (DGGE) bands. Bacterial communities in PM2.5 were mainly clustered (80%) into emergency and pre-emergency samples. The dominant phylum was Proteobacteria and most abundant genus was Novosphingobium, traditionally related to opportunistic respiratory diseases. The main factors associated with community structure were PM2.5, PM10 and carbon monoxide concentrations. This study exposed that bacterial community composition in Temuco varies according to AQIs, with the occurrence of potential opportunistic bacteria on heavily polluted days.

Spatiotemporal distributions and relationships of phosphorus content, phosphomonoesterase activity, and bacterial phosphomonoesterase genes in sediments from a eutrophic brackish water lake in Chile.

Phosphorus (P) cycling by microbial activity is highly relevant in the eutrophication of lakes. In this context, the contents of organic (Po) and inorganic (Pi) phosphorus, the activity of acid (ACP) and alkaline (ALP) phosphomonoesterase (Pase), and the abundances of bacterial Pase genes (phoD, phoC, and phoX) were studied in sediments from Budi Lake, a eutrophic coastal brackish water lake in Chile. Our results showed spatiotemporal variations in P fractions, Pase activities, and Pase gene abundances. In general, our results showed higher contents of Pi (110-144 mg kg-1), Po (512-576 mg kg-1), and total P (647-721 mg kg-1) in sediments from the more anthropogenized sampling sites in summer compared with those values of Pi (86-127 mg kg-1), Po (363-491 mg kg-1) and total P (449-618 mg kg-1) in less anthropogenized sampling sites in winter. In concordance, sediments showed higher Pase activities (µg nitrophenyl phosphate g-1 h-1) in sediments from the more anthropogenized sampling sites (9.7-22.7 for ACP and 5.9 to 9.6 for ALP) compared with those observed in less anthropogenized sampling sites in winter (4.2-12.9 for ACP and 0.3 to 6.7 for ALP). Higher abundances (gene copy g-1 sediment) of phoC (8.5-19 × 108), phoD (9.2-47 × 106), and phoX (8.5-26 × 106) genes were also found in sediments from the more anthropogenized sampling sites in summer compared with those values of phoC (0.1-1.1 × 108), phoD (1.4-2.4 × 106) and phoX (0.7-1.2 × 106) genes in the less anthropogenized sites in winter. Our results also showed a positive correlation between P contents, Pase activities, and abundances of bacterial Pase genes, independent of seasonality. The present study provided information on the microbial activity involved in P cycling in sediments of Budi Lake, which may be used in further research as indicators for the monitoring of eutrophication of lakes.

Case report: hepatitis in a child infected with SARS-CoV-2 presenting toll-like receptor 7 Gln11Leu single nucleotide polymorphism.

BACKGROUND: Covid-19 has the respiratory tract as the main target of infection, and patients present mainly dyspnea, pneumonia, dry cough, and fever. Nevertheless, organs outside the respiratory tract had been reported in recent studies, including the gastrointestinal tract and liver. The host innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through their pattern recognition receptor (PRRs). Toll-like receptor 7 (TLR-7) is a pattern recognition receptor recognizing ssRNA (SARS-CoV-2 is an ssRNA). Polymorphisms are characterized by two or more alternative forms of a distinct phenotype in the same population. Polymorphisms in tlrs genes can negatively influence the immune response to infectious diseases. There are several references in the literature to non-synonymous single nucleotide (rs) polymorphisms related to several genes. Some of them are important for the innate immunity, as rs 179008 (tlr-7), rs3775291 (tlr3), rs8177374 (tir domain-containing adaptor protein, tirap), rs1024611 (monocyte chemoattractant protein-1, mcp-1) and rs61942233 (2'-5'-oligoadenylate synthase-3, oas-3). CASE PRESENTATION: We identified a 5-year-old-male child with gastrointestinal symptoms and fever presenting acholic stool and jaundice, who was positive for SARS-CoV-2 IgM, IgA, and IgG and presenting the Gln11Leu rs 179008 in tlr-7. The child presented high levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, C-reactive protein, D-dimer, gamma-glutamyl transferase, alkaline phosphatase, and was negative for serological tests for hepatitis A, B, C, E, HIV 1 and 2, herpes virus, cytomegalovirus, Epstein-Barr virus, and negative for RTqPCR for Influenza A and B, RSV and SARS-CoV-2. We also investigated other SNPs in the tlr-3 (rs3775291), tirap (rs8177374), mcp-1 (rs1024611), and oas-3 (rs61942233) genes, and no mutation was detected. After an interview with the child's caregivers, any possible accidental ingestion of drugs or hepatotoxic substances was ruled out. CONCLUSION: To our knowledge, this is the first report of a SARS-CoV-2 caused hepatitis in a male child that has the tlr-7 Gln11Leu rs 179008, which could impair an efficient initial immune response. The knowledge of the patient's immune deficiency could improve the treatment to correct this deficiency with specific medications.

Composition and predicted functions of the bacterial community in spouting pool sediments from the El Tatio Geyser field in Chile.

The El Tatio Geyser Field (ETGF), located in Northern Chile, is the main geyser field in the southern hemisphere. Despite this, details of its microbial ecology are still unknown. Here, we briefly report on  the composition and predicted functions of the bacterial community in spouting pool sediments from the ETGF as revealed by high-throughput sequencing of 16S rRNA genes. Results of this analysis showed that while there were differences in richness and diversity between samples, bacterial communities were primarily dominated by the phyla Proteobacteria, followed Firmicutes, Bacteroidetes, Acidobacteria, and Chloroflexi. Analyses of predicted functional activity indicated that the functions were mostly attributed to chemoheterotrophy and aerobic chemoheterotrophy, followed by sulfur (respiration of sulfur compounds and sulfate) and nitrogen (nitrate reduction, respiration of nitrogen and nitrate) cycling. Taken together, our results suggest a high diversity in taxonomy and predictive functions of bacterial communities in sediments from spouting pools. This study provides fundamentally important  information on the structure and function  predictive functions of microbiota  communities in spouting pools. Moreover, since the ETGF is intensively visited and impacted by tens of thousands of tourists every year, our results can be used to help guide the design of sustainable conservation strategies.

Screening and Characterization of Phytases from Bacteria Isolated from Chilean Hydrothermal Environments.

Phytases are enzymes involved in organic phosphorus cycling in nature and widely used as feed additives in animal diets. Thermal tolerance is a desired property of phytases. The objectives of this study were to screen and characterize bacterial phytases from Chilean hydrothermal environments. In this study, 60% (30 of 63) of screened thermophilic (60 °C) isolates showed phytase activity in crude protein extracts. The characterization of phytase from two selected isolates (9B and 15C) revealed that both isolates produce phytases with a pH optimum at 5.0. The temperature optimum for phytate dephosphorylation was determined to be 60 and 50 °C for the phytases from the isolates 9B and 15C, respectively. Interestingly, the phytase from the isolate 15C showed a residual activity of 46% after incubation at 90 °C for 20 min. The stepwise dephosphorylation of phytate by protein extracts of the isolates 9B and 15C was verified by HLPC analysis. Finally, the isolates 9B and 15C were identified by partial sequencing of the 16S rRNA gene as members of the genera Bacillus and Geobacillus, respectively.

Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer.

BACKGROUND: Mammary cancer has a high incidence in canines and is an excellent model of spontaneous carcinogenesis. Molecular iodine (I2) exerts antineoplastic effects on different cancer cells activating re-differentiation pathways. In co-administration with anthracyclines, I2 impairs chemoresistance installation and prevents the severity of side effects generated by these antineoplastic drugs. This study is a random and double-blind protocol that analyzes the impact of I2 (10 mg/day) in two administration schemes of Doxorubicin (DOX; 30 mg/m2) in 27 canine patients with cancer of the mammary gland. The standard scheme (sDOX) includes four cycles of DOX administered intravenously for 20 min every 21 days, while the modified scheme (mDOX) consists of more frequent chemotherapy (four cycles every 15 days) with slow infusion (60 min). In both schemes, I2 or placebo (colored water) was supplemented daily throughout the treatment. RESULTS: mDOX attenuated the severity of adverse events (VCOG-CTCAE) in comparison with the sDOX group. The overall tumor response rate (RECIST criteria) for all dogs was 18% (interval of reduction 48-125%), and no significant difference was found between groups. I2 supplementation enhances the antineoplastic effect in mDOX, exhibiting a significant decrease in the tumor epithelial fraction, diminished expression of chemoresistance (MDR1 and Survivin) and invasion (uPA) markers and enhanced expression of the differentiation factor known as peroxisome proliferator-activated receptors type gamma (PPARγ). Significant tumor lymphocytic infiltration was also observed in both I2-supplemented groups. The ten-month survival analysis showed that the entire I2 supplementation (before and after surgery) induced 67-73% of disease-free survival, whereas supplementation in the last period (only after surgery) produced 50% in both schemes. CONCLUSIONS: The mDOX+I2 scheme improves the therapeutic outcome, diminishes the invasive capacity, attenuates the adverse events and increases disease-free survival. These data led us to propose mDOX+I2 as an effective treatment for canine mammary cancer.

Dendritic cells, macrophages, NK and CD8+ T lymphocytes play pivotal roles in controlling HSV-1 in the trigeminal ganglia by producing IL1-beta, iNOS and granzyme B.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) cause not only mild symptoms but also blindness and encephalitis. It was previously shown that the immune response against HSV-1 occurs mainly in the trigeminal ganglia (TG) and that Toll-like receptors 2 and 9 (TLR2/9) are important in mediating this response. It was also demonstrated that iNOS (nitric oxide synthase) and interleukin 1 beta (IL-1ß) play an essential role in the defense against HSV-1 infection. Importantly, the present work aimed to identify the primary cells responsible for iNOS and IL-1ß production and search for other important molecules and cells that might or might not depend on TLR2/9 receptors to mediate the immune response against HSV-1. METHODS: C57BL/6 (wild type, WT) and TLR2/9-/- mice were infected by the intranasal route with HSV-1 (1 × 106 p.f.u.). Cells were obtained from the TG and spleen tissues and the profile of immune cells was determined by flow cytometry in infected and mock infected WT and knockout mice. The percentage of cells producing iNOS, IL-1ß, granzyme B and perforin was also determined by flow cytometry. Chemokine monocyte chemoattractant protein-1 (MCP1) was measured by Cytometric Bead Array (CBA) in the TG, spleen and lung. Expression of type I interferons (IFNs), interleukins (IL) 5 and 10, IL-1ß and granzyme B were quantified by real time PCR. RESULTS: The results indicate that dendritic cells (DCs) and monocytes/macrophages (Mo/Mϕ) were the main sources of IL-1ß and iNOS, respectively, which, together with type I IFNs, were essential for the immune response against HSV-1. Additionally, we showed that granzyme B produced by CD8+ T and NK lymphocytes and MCP-1 were also important for this immune response. Moreover, our data indicate that the robust production of MCP-1 and granzyme B is either TLR-independent or down regulated by TLRs and occurs in the TG of TLR2/9-/- infected mice. CONCLUSION: Taken together, our data provide strong evidence that the responses mediated by DCs, Mo/Mϕ, NK and CD8+ T lymphocytes through IL-1ß, iNOS and granzyme B production, respectively, together with the production of type I IFN early in the infection, are crucial to host defense against HSV-1.

Defense against HSV-1 in a murine model is mediated by iNOS and orchestrated by the activation of TLR2 and TLR9 in trigeminal ganglia.

BACKGROUND: Herpes simplex 1 (HSV-1) causes various human clinical manifestations, ranging from simple cold sores to encephalitis. Innate immune cells recognize pathogens through Toll-like receptors (TLRs), thus initiating the immune response. Previously, we demonstrated that the immune response against HSV-1 is dependent on TLR2 and TLR9 expression and on IFN gamma production in the trigeminal ganglia (TG) of infected mice. In this work, we further investigated the cells, molecules, and mechanisms of HSV-1 infection control, especially those that are TLR-dependent. METHODS: C57BL/6 wild-type (WT), TLR2-/-, TLR9-/-, and TLR2/9-/- mice were intranasally infected with HSV-1. On the viral peak day, the TG and brains were collected from mice and TLR expression was measured in the TG and brain and inducible nitric oxide synthase (iNOS) expression was measured in the TG by real-time PCR. Immunofluorescence assays were performed in mice TG to detect iNOS production by F4/80+ cells. Intraperitoneal macrophages nitric oxide (NO) production was evaluated by the Griess assay. WT, CD8-/-, RAG-/-, and iNOS-/- mice were intranasally infected in a survival assay, and their cytokine expression was measured in the TG by real-time PCR. RESULTS: Infected WT mice exhibited significantly increased TLR expression, compared with their respective controls, in the TG but not in the brain. TLR-deficient mice had moderately increased TLR expression in the TG and brain in compare with the non-infected animals. iNOS expression in the WT infected mice TG was higher than in the other groups with increased production by macrophages in the WT infected mice, which did not occur in the TLR2/9-/- mice. Additionally, the intraperitoneal macrophages of the WT mice had a higher production of NO compared with those of the TLR-deficient mice. The CD8-/-, RAG-/-, and iNOS-/- mice had 100% mortality after the HSV-1 infection compared with 10% of the WT mice. Cytokines were overexpressed in the iNOS-/- infected mice, while the RAG-/- mice were nearly unresponsive to the virus. CONCLUSION: TLRs efficiently orchestrate the innate immune cells, eliciting macrophage response (with NO production by the macrophages), thereby controlling the HSV-1 infection through the immune response in the TG of mice.

Influence of single nucleotide polymorphisms in factor VIII and von Willebrand factor genes on plasma factor VIII activity: the ARIC Study.

Factor VIII (FVIII) functions as a cofactor for factor IXa in the contact coagulation pathway and circulates in a protective complex with von Willebrand factor (VWF). Plasma FVIII activity is strongly influenced by environmental and genetic factors through VWF-dependent and -independent mechanisms. Single nucleotide polymorphisms (SNPs) of the coding and promoter sequence in the FVIII gene have been extensively studied for effects on FVIII synthesis, secretion, and activity, but impacts of non-disease-causing intronic SNPs remain largely unknown. We analyzed FVIII SNPs and FVIII activity in 10,434 healthy Americans of European (EA) or African (AA) descent in the Atherosclerosis Risk in Communities (ARIC) study. Among covariates, age, race, diabetes, and ABO contributed 2.2%, 3.5%, 4%, and 10.7% to FVIII intersubject variation, respectively. Four intronic FVIII SNPs associated with FVIII activity and 8 with FVIII-VWF ratio in a sex- and race-dependent manner. The FVIII haplotypes AT and GCTTTT also associated with FVIII activity. Seven VWF SNPs were associated with FVIII activity in EA subjects, but no FVIII SNPs were associated with VWF Ag. These data demonstrate that intronic SNPs could directly or indirectly influence intersubject variation of FVIII activity. Further investigation may reveal novel mechanisms of regulating FVIII expression and activity.

Impact of Toll-Like Receptors (TLRs) and TLR Signaling Proteins in Trigeminal Ganglia Impairing Herpes Simplex Virus 1 (HSV-1) Progression to Encephalitis: Insights from Mouse Models.

Herpes simplex virus 1 (HSV-1) or simplexvirus humanalpha 1 is a neurotropic virus that is responsible for orofacial infections in humans. More than 70% of the world's population may have seropositivity for HSV-1, and this virus is a leading cause of sporadic lethal encephalitis in humans. The role of toll-like receptors (TLRs) in defending against HSV-1 infection has been explored, including the consequences of lacking these receptors or other proteins in the TLR pathway. Cell and mouse models have been used to study the importance of these receptors in combating HSV-1, how they relate to the innate immune response, and how they participate in the orchestration of the adaptive immune response. Myeloid differentiation factor 88 (MyD88) is a protein involved in the downstream activation of TLRs and plays a crucial role in this signaling. Mice with functional MyD88 or TLR2 and TLR9 can survive HSV-1 infection. However, they can develop encephalitis and face a 100% mortality rate in a dose-dependent manner when MyD88 or TLR2 plus TLR9 proteins are non-functional. In TLR2/9 knockout mice, an increase in chemokines and decreases in nitric oxide (NO), interferon (IFN) gamma, and interleukin 1 (IL-1) levels in the trigeminal ganglia (TG) have been correlated with mortality.

Colon and Rectal Surgery Fellowship Applicant and Matching Trends in the United States: An Analysis of National Resident Matching Program Data.

BACKGROUND: Colon and Rectal Surgery fellowships are training programs that aim to train surgeons in the management of small bowel, colon, rectal, and anal pathologies. OBJECTIVE: We investigated trends in Colon and Rectal Surgery fellowship match to help applicants anticipate future fellowship application cycles. DESIGN: This was a retrospective cohort study of applicants in the Colon and Rectal Surgery match from 2009 to 2023. Proportion of positions filled, match rates, and rank-order lists were collected. The impact of US-MD, non-US-MD, and DO status on match rate was assessed. We used the Mann Kendall trend test to obtain tau statistic and P-value for temporal trends over time, while associations between categorical variables were investigated by a chi-square test. RESULTS: Fellowship programs increased from 43 to 67, positions increased from 78 to 110, and number of applicants rose from 113 to 135. Nearly all positions were filled from 2009 to 2023 (range: 96.3%-100%). The overall match rate fluctuated between 67.3% and 80.7%. The match rate over the past 5 years was 72.0%. The match rate for US-MDs was 80.0%, while non-US-MDs had a 56.2% match rate. The percentage matching at each rank were first choice 28.0%, second choice 10.4%, third choice 6.9%, and fourth choice or lower 23.5%. CONCLUSION: Despite an increase in Colon and Rectal Surgery fellowship positions, the overall match rate has not changed significantly over the years, mainly as a result of increased applicants.

Environmental evaluation of the Reloncaví estuary in southern Chile based on lipophilic shellfish toxins as related to harmful algal blooms.

The Reloncaví estuary in southern Chile is famous for its aquaculture. However, recurring harmful algal blooms have adversely affected mussel production. Therefore, regular monitoring of algal toxins is urgently needed to better understand the contamination status of the estuary. In this study, we quantified 15 types of lipophilic shellfish toxins in Metri Bay in the Reloncaví estuary on a biweekly basis for 4 years. We identified algal species using microscopy and metabarcoding analysis. We also measured water temperature, salinity, chlorophyll-a, and dissolved oxygen to determine the potential relationships of these parameters with algal toxin production. Our results revealed the presence of a trace amount of pectenotoxin and the causal phytoplankton Dinophysis, as well as yessotoxin and the causal phytoplankton Protoceratium. Statistical analysis indicated that fluctuations in water temperature affected the detection of these toxins. Additionally, metabarcoding analysis detected the highly toxic phytoplankton Alexandrium spp. in some samples. Although our results suggest that the level of lipophilic shellfish toxins in Metri Bay during the study period was insignificantly low using our current LC-MS method, the confirmed presence of highly toxic algae in Metri Bay raises concerns, given that favorable environmental conditions could cause blooms.

Enhancing the epidemiological surveillance of SARS-CoV-2 using Sanger sequencing to identify circulating variants and recombinants.

Since the emergence of SARS-CoV-2 in December 2019, more than 12,000 mutations in the virus have been identified. These could cause changes in viral characteristics and directly impact global public health. The emergence of variants is a great concern due to the chance of increased transmissibility and infectivity. Sequencing for surveillance and monitoring circulating strains is extremely necessary as the early identification of new variants allows public health agencies to make faster and more effective decisions to contain the spread of the virus. In the present study, we identified circulating variants in samples collected in Belo Horizonte, Brazil, and detected a recombinant lineage using the Sanger method. The identification of lineages was done through gene amplification of SARS-CoV-2 by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). By using these specific fragments, we were able to differentiate one variant of interest and five circulating variants of concern. We were also able to detect recombinants. Randomly selected samples were sequenced by either Sanger or Next Generation Sequencing (NGS). Our findings validate the effectiveness of Sanger sequencing as a powerful tool for monitoring variants. It is easy to perform and allows the analysis of a larger number of samples in countries that cannot afford NGS.

Antifibrotic activity of carbon quantum dots in a human in vitro model of non-alcoholic steatohepatitis using hepatic stellate cells.

Around 33% of the global population suffers from non-alcoholic fatty liver disease (NAFLD). From these patients, 30% of them progress into non-alcoholic steatohepatitis (NASH), the critical point where lack of treatment leads to cirrhosis and hepatic failure. Moreover, to date, there are no approved therapeutic options available for NASH. It is known that hepatic stellate cell (HSC) activation contributes the most to hepatic disfunction, leading to reactive oxygen species (ROS) accumulation and chronic inflammation, and that the use of nanomaterials to deliver antioxidants may have potential to reduce the activity of activated HSCs. Therefore, we implemented a human in vitro co-culture model in which we take into consideration two factors related to NASH and fibrosis: human hepatic stellate cells from a NASH diagnosed donor (HHSC-N) and peripheral blood mononuclear cells (PBMCs), particularly lymphocytes. The co-cultures were treated with: (1) carbon quantum dots (CD) or (2) lactoferrin conjugated CD (CD-LF) for 24 h or 72 h. CD and CD-LF treatments significantly downregulated profibrotic genes' expression levels of ACTA2, COL1A1, and TIMP1 in co-cultured HHSC-N at 72 h. Also, we assayed the inflammatory response by quantifying the concentrations of cytokines IL-22, IL-10, IFN-γ and IL-4 present in the co-culture's conditioned media whose concentrations may suggest a resolution-associated response in progress. Our findings may serve as a starting point for the development of a NASH treatment using bio-nanotechnology.

Identification of bacteria in potential mutualism with toxic Alexandrium catenella in Chilean Patagonian fjords by in vitro and field monitoring.

The dinoflagellate Alexandrium catenella is a well-known paralytic shellfish toxin producer that forms harmful algal blooms, repeatedly causing damage to Chilean coastal waters. The causes and behavior of algal blooms are complex and vary across different regions. As bacterial interactions with algal species are increasingly recognized as a key factor driving algal blooms, the present study identifies several bacterial candidates potentially associated with Chilean Alexandrium catenella. This research narrowed down the selection of bacteria from the Chilean A. catenella culture using antibiotic treatment and 16S rRNA metabarcoding analysis. Subsequently, seawater from two Chilean coastal stations, Isla Julia and Isla San Pedro, was monitored for two years to detect Alexandrium species and the selected bacteria, utilizing 16S and 18S rRNA gene metabarcoding analyses. The results suggested a potential association between Alexandrium species and Spongiibacteraceae at both stations. The proposed candidate bacteria within the Spongiibacteraceae family, potentially engaging in mutualistic relationships with Alexandrium species, included the genus of BD1-7 clade, Spongiibbacter, and Zhongshania.

Evaluation of different supportive treatments during packed cell volume replacement in calves naturally infected with tick fever agents.

This study evaluated the effect of different supportive treatments on PCV replacement of dairy calves naturally infected with tick fever (TF) agents, and treated with diminazene and enrofloxacin. Five products were tested as supportive treatments in four experiments. In these experiments, we used Girolando female calves (Gyr × Holstein, genetic ratio of 15/16 and 31/32 Holstein) four to six months old, raised in pasture, naturally infected with TF agents, and infested with R. microplus. Supportive treatment was administered once on day 0 of the study concurrently with specific treatment targeting TF agents. The animals were observed on days 0, 3, and 7. Oral or intravenous administration of a vitamin complex and mineral salts enhanced the increase in PCV and biochemical analytes present in the serum of calves naturally infected with TF agents. No positive effect on PCV values was observed with the administration of (1) invigorating tonic: calcium, casein-peptides and vitamin B12, (2) iron-based stimulant tonic and (3) metabolic tonic: vitamin A, vitamin D, and a fraction of polyunsaturated fatty acids. Supplementation by injection with Type III iron resulted in increased hemoglobin and PCV in treated animals. However, these results did not occur with iron citrate. Therefore, more studies with Type III iron need to be performed. Supportive treatment conferred no advantage in animals with no history of reduced PCV.