Genomic analysis of the MLST population structure and antimicrobial resistance genes associated with Salmonella enterica in Mexico.

Salmonella enterica is one of the most commonly reported foodborne pathogens by public health agencies worldwide. In this study, the multilocus sequence typing (MLST) population structure and frequency of antimicrobial resistance (AMR) genes were evaluated in S. enterica strains from Mexico (n = 2561). The most common sources of isolation were food (44.28%), environment (27.41%), animal-related (24.83%), and human (3.48%). The most prevalent serovars were Newport (8.51%), Oranienburg (7.03%), Anatum (5.78%), Typhimurium (5.12%), and Infantis (4.57%). As determined by the 7-gene MLST scheme, the most frequent sequence types were ST23, ST64, and ST32. The core genome MLST scheme identified 132 HC2000 and 195 HC900 hierarchical clusters, with the HC2000_2 cluster being the most prevalent in Mexico (n = 256). A total of 78 different AMR genes belonging to 13 antimicrobial classes were detected in 638 genomic assemblies of S. enterica. The most frequent class was aminoglycosides (31.76%), followed by tetracyclines (12.53%) and sulfonamides (11.91%). These results can help public health agencies in Mexico prioritize their efforts and resources to increase the genomic sequencing of circulating Salmonella strains. Additionally, they provide valuable information for local and global public health efforts to reduce the impact of foodborne diseases and AMR.

Risk ranking of food categories associated with Salmonella enterica contamination in the central region of Mexico.

To prevent and control foodborne diseases, there is a fundamental need to identify the foods that are most likely to cause illness. The goal of this study was to rank 25 commonly consumed food products associated with Salmonella enterica contamination in the Central Region of Mexico. A multicriteria decision analysis (MCDA) framework was developed to obtain an S. enterica risk score for each food product based on four criteria: probability of exposure to S. enterica through domestic food consumption (Se); S. enterica growth potential during home storage (Sg); per capita consumption (Pcc); and food attribution of S. enterica outbreak (So). Risk scores were calculated by the equation Se*W1 +Sg*W2 +Pcc*W3 +So*W4 , where each criterion was assigned a normalized value (1-5) and the relative weights (W) were defined by 22 experts' opinion. Se had the largest effect on the risk score being the criterion with the highest weight (35%; IC95% 20%-60%), followed by So (24%; 5%-50%), Sg (23%; 10%-40%), and Pcc (18%; 10%-35%). The results identified chicken (4.4 ± 0.6), pork (4.2 ± 0.6), and beef (4.2 ± 0.5) as the highest risk foods, followed by seed fruits (3.6 ± 0.5), tropical fruits (3.4 ± 0.4), and dried fruits and nuts (3.4 ± 0.5), while the food products with the lowest risk were yogurt (2.1 ± 0.3), chorizo (2.1 ± 0.4), and cream (2.0 ± 0.3). Approaches with expert-based weighting and equal weighting showed good correlation (R2  = 0.96) and did not show significant differences among the ranking order in the top 20 tier. This study can help risk managers select interventions and develop targeted surveillance programs against S. enterica in high-risk food products.

Salmonella enterica in Mexico 2000-2017: Epidemiology, Antimicrobial Resistance, and Prevalence in Food.

In Mexico, information of Salmonella enterica cases linked to food consumption is scarce. The objective of this article was to assess how S. enterica affect public health in Mexico. To conduct this study, data on the epidemiology of nontyphoidal S. enterica (NTS), Salmonella Typhi, and Salmonella Paratyphi A collected from 2000 to 2017 through the National Epidemiological Surveillance System of Mexico (Sistema Nacional de Vigilancia Epidemiológica de Mexico [SINAVE]) were used. Geographical distribution, season, age groups, and gender were variables considered to analyze S. enterica incidence. An estimation of cases caused by S. enterica in Mexico was calculated while considering data underestimation and the proportion of foodborne diseases. Information of the prevalence of the pathogen in food and the antimicrobial resistance of isolates from food and human cases were obtained from published studies. Outbreaks of S. enterica derived from imported Mexican products in the Unites States are discussed. In 2017, the numbers of reported cases of NTS (92,013) were two and seven times higher than the reported cases of Salmonella Typhi (45,280) and Salmonella Paratyphi A (12, 458). The NTS incidence was higher in lower socioeconomic Mexican regions. The gaps in the surveillance system make it impossible to establish a reliable tendency among age groups, geographical distribution, and gender. In 2017, the estimated frequency of NTS foodborne cases was 49 times higher than that reported in SINAVE, whereas for Salmonella Typhi and Salmonella Paratyphi A it was 23 times. Fresh meat showed the highest prevalence of S. enterica, and most of their isolates had multidrug resistance. Salmonella Typhimurium was the most common serotype isolated from human cases and food. Food safety agencies in Mexico need to prioritize efforts and resources to establish guidelines to ensure the absence of S. enterica in food.

Ciliated columnar epithelium in the esophagus and gastroesophageal junction: A different perspective from study of a North American population.

An index case of ciliated columnar epithelium in a gastroesophageal (GE) junction biopsy identified in routine surgical pathology practice struck us as highly unusual. However, pathology literature, mainly from Asian populations, reports ciliated columnar epithelium in up to 40% of tissue samples from the upper GI tract. This was inconsistent with our pathology practice experience, so we initiated a local review of cases at our Canadian centre. 1048 consecutive tissue samples from the esophagus and GE junction were reviewed retrospectively and no ciliated epithelium was identified. This review included 1000× oil immersion microscopy of 22 cases with "multilayered epithelium". In 971 cases verified in prospective surgical pathology practice following identification of the index case, 3 additional cases of ciliated columnar epithelium were identified. The index case had ciliated pseudostratified columnar epithelium, resembling respiratory epithelium, and had strong, diffuse expression of TTF-1 by immunohistochemistry. In the other 3 cases, the cilia were located on the surface of a pseudostratified columnar epithelium, a multilayered epithelium, or a low columnar epithelium, all TTF-1 negative. Over a year later, the index case proved to have arisen from a bronchial-esophageal fistula. The other cases were not associated with a fistula. Our conclusion is that ciliated columnar epithelium is rare in Canadian adults (<0.5% of patients). Ciliated epithelium due to a bronchial-esophageal fistula is exceptional, but something to consider if there is a suspicious clinical picture and TTF-1 expression. Other cases might represent a rare metaplastic phenomenon or remnant from fetal development.

An Improve Protocol for PCR Using LM1 and LM2 Primers for Listeria monocytogenes Detection in Food Matrices.

Several studies have observed that a conventional PCR protocol using primers LM1 and LM2 for the identification of gene hlyA Listeria monocytogenes generates non-specific PCR amplifications and false positives. For this reason in this study, we provide a modified PCR protocol that improves the specificity of the LM1 and LM2 primers.

Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway.

PURPOSE: The endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1. METHODS: Whole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data. RESULTS: All patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele. CONCLUSION: NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum-associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.

Incongruence of Hemolysis, Elevated Liver Enzyme, Low-Platelet Count Syndrome (HELLP) and Preeclampsia Criteria in Pregnancy: Implications for Medical Education and Obstetrics Training.

There is conflicting information in the medical literature regarding hemolysis, elevated liver enzymes, low platelet count syndrome (HELLP) and preeclampsia and whether they are subsets of a single disease or distinct complications of pregnancy. In numerous places, HELLP is described as a severe form or later stage of preeclampsia. However, a detailed medical literature search utilizing NCBI, PubMed, and Elicit: The AI Research Assistant clearly demonstrates that HELLP and preeclampsia are distinct diseases. While they share similarities, each one has unique diagnostic criteria, pathophysiology, and treatment. We believe that these entities should be taught as separate entities to medical students and residents because this will result in better patient care. Medical educational theories, including constructivism, demonstrate that initial learning experiences heavily influence future learning. The joining of HELLP and preeclampsia in medical school teaching materials is detrimental to students' and trainees' long-term understanding of these two serious complications of pregnancy.

Genomic diversity of Salmonella enterica isolated from raw chicken at retail establishments in Mexico.

The genomic diversity of circulating non-typhoidal Salmonella in raw chicken was investigated in three states of central Mexico. A total of 192 S. enterica strains from chicken meat samples collected at supermarkets, fresh markets, and butcher shops were analyzed by whole-genome sequencing. The serovar distribution, occurrence of genes encoding for antimicrobial resistance, metal resistance, biocide resistance, plasmids and virulence factors, and clonal relatedness based on single nucleotide polymorphism (SNP) analysis were investigated. Serovars Infantis, Schwarzengrund and Enteritidis predominated among twenty identified. The distribution of serovars and proportion of AMR genes was different according to the state, year, season, and retail establishment (p < 0.001). Genes encoding metals resistance were identified in all the strains. A total of 145 virulence genes were identified and strains were classified into 32 virulotypes; serovars Infantis, Typhimurium, and Enteritidis showed the highest number of virulence genes. The strains matched 34 SNP clusters in the NCBI Pathogen Detection server and 59 %, which corresponded to Infantis, Schwarzengrund, Saintpaul, and Enteritidis, were associated with five major clusters and matched with chicken, environmental and clinical isolates from at least three countries. These results provide useful information to understand the epidemiology of Salmonella, conduct microbial risk assessment, and design risk-based control measures.

Linking intraspecies variability of Salmonella enterica isolates under acidic conditions to genotype.

There is a lack of information about Salmonella enterica strains under acidic conditions and their association with their genome. This study characterized intraspecies variability in the growth of 167 S. enterica isolates under two acid conditions (pH 4 and 5) and linked to the whole genome sequencing (WGS) data. A total of 1002 curves for each condition were obtained using turbidimetry measurements, and Baranyi and Roberts model was used to estimate the maximum rate of change (rcmax; OD600 nm h-1). Strains were categorized into slow, intermediate, and fast; and associations with their WGS data were performed. Huge variability in r c max ¯ $\overline {{\mathrm{r}}{{{\mathrm{c}}}_{{\mathrm{max}}}}} $ was observed at both conditions (pH 5 = 0.016-0.066 OD600nm h-1 and pH 4 = 0.003-0.028 OD600nm h-1). The majority of isolates was classified as intermediate r c max ¯ $\overline {{\mathrm{r}}{{{\mathrm{c}}}_{{\mathrm{max}}}}} $ (59.5% at pH 5 and 46.1% at pH 4). Strains classified as fast had a low frequency of allABCD genes at both pHs, and any of them having the presence of pefABCD, spvBCR, aadA2, dfrA12, and gyrA_D87G genes were linked to virulence or antimicrobial resistance. This study suggests that strains with fast capacity for growth under acidic conditions could have a fitness cost in their virulence or resistance potential. PRACTICAL APPLICATION: Data presented in this study could be used to select representative strains to evaluate the exposure assessment in different food items, mainly the growth and survival in acidic foods.

COVID-19 and Placental Infection: Are Fetal Survivors at Risk of Long-Term Cardiovascular Complications?

As we enter the fourth year of the coronavirus disease 2019 (COVID-19) pandemic, it has become obvious that adult survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are susceptible to numerous complications in various organ systems. SARS-CoV-2 placental infection is an unanticipated complication of COVID-19 during pregnancy. We hypothesize that fetal survivors of SARS-CoV-2 placentitis are susceptible to long-term cardiovascular complications.

The Role of Medication, Mental Illness, and Social Isolation on the Development of the Fetus in the Context of the COVID-19 Pandemic.

As we enter the COVID-19 post-pandemic period, uncertainty surrounds the impact of the varied effects of medications, mental illness, and social isolation on children born during the pandemic. Medications like selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines during pregnancy, coupled with pandemic-induced social isolation, may contribute to anxiety, depression, and behavioral issues in the offspring. Supporting evidence shows SSRIs' influence on brain development, while third-trimester benzodiazepine use may lead to neonatal withdrawal syndrome. Social isolation during the pandemic has also been linked to increased maternal depression and anxiety. This editorial emphasizes the need for increased surveillance in educational settings and early behavioral assessments by pediatricians. Further research is required to understand the long-term effects of maternal SSRIs. This knowledge can aid in timely interventions to protect the well-being of children born during COVID-19.

Postinfantile Giant Cell Hepatitis Secondary to Rheumatoid Arthritis.

Postinfantile giant cell hepatitis (PIGCH), also known as syncytial giant cell hepatitis, continues to be a poorly defined and rare disease presentation in the adult population. Although a common finding in neonates, there is limited literature on the disease process, causes, and treatment success of PIGCH in adults. A strong association between autoimmune disorders and PIGCH, considerably so in the case of autoimmune hepatitis, has been established. However, there have been limited to no reports of PIGCH secondary to rheumatoid arthritis. Our clinical case aims to bring forth a vignette of PIGCH to spotlight this ill-defined disease in the adult population and highlight some of the proposed causes, treatments, and laboratory markers.

Identification of t(1;19)(q12;p13) and ploidy changes in an ependymosarcoma: a cytogenetic evaluation.

Gliosarcoma, a recognized subtype of glioblastoma, is a biphasic tumor exhibiting distinct glial and sarcomatous components. Ependymosarcomas are rarer, biphasic ependymal tumors exhibiting sarcomatous change. Genetic abnormalities associated with this curious phenotype are not well understood. We are presenting the first karyotype of ependymosarcoma with identification of a clonal t(1;19)(q12;p13). Fluorescence in situ hybridization (FISH) was performed with a probe set targeting 1q23 and 19p13.3. Although the tumor did not show evidence of t(1;19)(q23;p13.3) by FISH, increased ploidy was a feature of the sarcomatous component. On clinical followup the patient is doing well without evidence of recurrence 55 months after initial resection, and postoperative treatment with irradiation and temozolomide. The significance of the genetic alterations we describe associated with sarcomatoid change in ependymal neoplasms, and ultimately their prognostic relevance, merits further study.

Homozygous UNC13A Variant in an Infant With Congenital Encephalopathy and Severe Neuromuscular Phenotype: A Case Report With Detailed Central Nervous System Neuropathologic Findings.

Uncoordinated 13 (UNC13A) affects movement in Caenorhabditis elegans (C. elegans). It is responsible for docking, priming, and stabilizing synaptic vesicle fusion complexes in the neuronal synapse and neuromuscular junction (NMJ). It also plays an important role in central nervous system development. We report the detailed clinical history and central nervous system neuropathologic findings in an infantile case with homozygous UNC13A loss of function variant, in order to advance the understanding of this critically important synaptic vesicle protein. This is the first detailed central nervous system neuropathologic report of this rare case of homozygous UNC13A loss.

Genotypic and phenotypic quantitative microbial risk assessment model of human salmonellosis related to the consumption of chicken meat in the central region of Mexico.

Chicken meat is often associated withSalmonella entericacontamination worldwide. This study proposes a risk assessment model for human salmonellosis linked to the domestic consumption of chicken meat in the central region of Mexico, incorporating genotypic and phenotypic data. SixS. entericagroups were used, considering the presence of specific virulence genes and multidrug resistance (MDR). Sixteen exposure scenarios were established considering retail point (RP1 = fresh market/butcher shop; RP2 = mini-super/supermarket), transportation, home storage, cooking, and cross-contamination. The model predicted a mean annual salmonellosis cases of 66,754 due to chicken consumption (CI95% 10775-231606). The mean probability of illness (Pill) among the exposure scenarios ranged from 2.5 × 10-9 to 3.7 × 10-6, 7.7 × 10-8 to 1.1 × 10-4, and 6.7 × 10-4 to 7.8 × 10-2 for low, moderate, and high virulence groups. Exposure scenarios with the highest Pill were not responsible for most cases due to their low frequency of occurrence. The high virulence/ MDR group was responsible for most cases (66.5 %), despite the low S. enterica prevalence (RP1 0.5 % and RP2 5.0 %). The years lost due to disability (YLD) value for MDR was 2.6 × higher than for non-MDR. Spearman rank showed that the inputs with higher influence on the variability of salmonellosis depended on the type of exposure scenario. For example, the cooking temperature and time had the most significant influence in the scenarios where S. enterica can survive after cooking. Including the microbial genotypic and phenotypic characteristics in risk assessment modeling highlights the importance of focusing on high-virulent and MDR strains, which are not the most frequent but represent the highest public health risk.

Comparative Study between Two Simple Synthesis Methods for Obtaining Green Gold Nanoparticles Decorating Silica Particles with Antibacterial Activity.

The SiO2 particles system is one of the most common ways to protect colloidal metal systems, such as gold nanoparticles, from aggregation and activity loss due to their high chemical stability and low reactivity. In this study, silica green gold nanoparticles (AuNPs synthesized with mullein extract) were fabricated using two different sol-gel methods. The nanoparticles were characterized by Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), Fourier Transformed Infrared (FTIR), and the antibacterial activity against pathogens (Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella enterica). Synthesis-1 nanoparticles had a kidney-shaped form and uniform distribution, while synthesis-2 nanoparticles had a spherical and non-uniform form. Characterization showed that temperature is an important factor in the distribution of AuNPs in silica; a decrease allowed the formation of Janus-type, and an increase showed a higher concentration of gold in energy-dispersive spectroscopy (EDS) analysis. Overall, similar bands of the two synthesis silica nanoparticles were observed in FTIR, while XRD spectra showed differences in the preferential growth in AuNPs depending on the synthesis. Higher antibacterial activity was observed against S. aureus, which was followed by L. monocytogenes. No differences were observed in the antibacterial activity between the two different sol-gel methods.

Detection, quantification, and characterization of Salmonella enterica in mango, tomato, and raw chicken purchased in the central region of Mexico.

To estimate human exposure to Salmonella enterica, it is essential to understand the pathogen distribution and characteristics. Prevalence and concentration of S. enterica were determined in mango, tomato, and raw chicken samples purchased in three states (Aguascalientes, Querétaro, and Guadalajara) located in the central region of Mexico during two seasons. In addition, S. enterica isolates were characterized by absence/presence of 13 virulence genes (chromosomal, prophage, and plasmid) and resistance to 14 antibiotics. A total of 300 samples of mango, 272 of tomato, and 354 of raw chicken were analyzed. The mean of the prevalence (24.9%) and concentration (-0.61 Log MPN/g) of S. enterica in chicken was higher than in mango (1.3%, -1.7 Log MPN/g) and tomato (1.1%, -1.7 Log MPN). Among S. enterica isolates (284), there were 7 different virulotypes, belonging 68.7% of isolates to V2; there was high variability in the presence of mobile genetic elements. The occurrence of specific mobile elements ranged from 81.4% to 11.3% among isolates. Among the isolates, 91.5% were resistant to at least one antibiotic with ampicillin being the most frequent; 54.9% of isolates were multidrug resistant. Data from this study can be used for quantitative microbial risk assessment of S. enterica related to mango, tomato, and raw chicken consumption in the central region of Mexico. PRACTICAL APPLICATION: Data on the prevalence and concentration of Salmonella enterica obtained in this study can be used to estimate the exposure assessment for the consumption of mango, tomato, and chicken in the central region of Mexico. In addition, the characteristics of the S. enterica isolates could be used to select representative strains for future studies to evaluate the intraspecies variability.

Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas.

'Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly EWSR1-ATF1 and EWSR1-CREB1 fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with CREM as the fusion partner (either EWSR1-CREM or FUS-CREM). Group A tumors more often demonstrated stellate/spindle cell morphology and hemangioma-like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid/rhabdoid morphology without hemangioma-like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression-free survival relative to Group A tumors (median 4.5 vs. 49 months, p = 0.001). Together, these findings confirm that intracranial AFH-like neoplasms and IMMT represent histologic variants of a single tumor type ('intracranial mesenchymal tumor, FET-CREB fusion-positive') that is distinct from meningioma and extracranial sarcomas. Additionally, epigenomic evaluation may provide important prognostic subtyping for this unique tumor entity.