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The continuous quest for improved specifications of optical dew-point hygrometers has raised customer expectations on the performance of these devices. In the absence of a long calibration history, users with a limited prior experience in the measurement of humidity, place reliance on manufacturer specifications to estimate long-term stability. While this might be reasonable in the case of measurement of electrical quantities, in humidity it can lead to optimistic estimations of uncertainty. This article reports a study of the long-term stability of some hygrometers and the analysis of their performance as monitored through regular calibration. The results of the investigations provide some typical, realistic uncertainties associated with the long-term stability of instruments used in calibration and testing laboratories. Together, these uncertainties can help in establishing initial contributions in uncertainty budgets, as well as in setting the minimum calibration requirements, based on the evaluation of dominant influence quantities. [ABSTRACT FROM AUTHOR]

Pan-resistant Acinetobacter baumannii have prompted the search for therapeutic alternatives. We evaluate the efficacy of four cecropin A-melittin hybrid peptides (CA-M) in vivo. Toxicity was determined in mouse erythrocytes and in mice (lethal dose parameters were LD, LD, LD). Protective dose 50 (PD) was determined by inoculating groups of ten mice with the minimal lethal dose of A. baumannii (BMLD) and treating with doses of each CA-M from 0.5 mg/kg to LD. The activity of CA-Ms against A. baumannii was assessed in a peritoneal sepsis model. Mice were sacrificed at 0 and 1, 3, 5, and 7-h post-treatment. Spleen and peritoneal fluid bacterial concentrations were measured. CA(1-8)M(1-18) was the less haemolytic on mouse erythrocytes. LD (mg/kg) was 32 for CA(1-8)M(1-18), CA(1-7)M(2-9), and Oct-CA(1-7)M(2-9), and 16 for CA(1-7)M(5-9). PD was not achieved with non-toxic doses (≤LD). In the sepsis model, all CA-Ms were bacteriostatic in spleen, and decreased bacterial concentration ( p < 0.05) in peritoneal fluid, at 1-h post-treatment; at later times, bacterial regrowth was observed in peritoneal fluid. CA-Ms showed local short-term efficacy in the peritoneal sepsis model caused by pan-resistant Acinetobacter baumannii. [ABSTRACT FROM AUTHOR]

Abstract: Antimicrobial agents have a major practical importance in food, pharmaceutical and cosmetic applications for preventing contamination. Our group has developed a novel class of cationic diacyl glycerol arginine-based surfactants denoted 1414RAc and 1212RAc. To assess the antimicrobial properties of these new surfactants we have studied how they interact with 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) and 1,2-dimiristoyl-sn-glycero-3-phosphocoline (DMPC) as model membranes, as well with living organisms endowed or not with external barriers, such as gram negative bacteria, the human protozoa Leishmania and mammalian cell line. The structure and phase characteristics of mixed monolayers have been assessed through the analysis of static elasticity. The extent of component miscibility of surfactant and phospholipid in mixed monolayers has been studied using the additivity rule and the excess free energy of a mixture as a function of the phospholipid molar fraction for different surface pressure values. In all the mixtures studied, the mixed monolayer is thermodynamically favoured except for the 1212RAc/DMPC case that exhibits positive values of excess free energy. The interaction with living cells has cytotoxic effects only in eukaryotic cells, by unspecific membrane permeabilization. [Copyright &y& Elsevier]

The objective of this study was to determine risk factors and sources attributed to yersiniosis in Aotearoa New Zealand (NZ). A risk factor questionnaire was administered to 247 notified yersiniosis cases and 258 control participants from the Canterbury and/or Wellington regions of NZ. Yersinia sp. isolates from clinical cases and a range of food sources were whole-genome sequenced and genetically compared. Yersinia enterocolitica (YE) bioserotype 2/3, O:9 [McNally multi-locus sequence type (ST) 12] and YE Biotype (BT) 1A (46 different STs) predominated within the consented cases (45 and 27%, respectively). Exposure to pork was identified as a significant risk factor for cases associated with YE ST12. The presence of YE ST12 was confirmed in retail raw meat, primarily raw pork. Single-nucleotide polymorphism (SNP) analysis identified multiple genomically very closely related clusters (0-5 SNPs) of YE ST12, predominately from raw pork with clinical cases from one or both regions. Risk factors associated with YE BT 1A included the consumption of cooked seafood, sushi, tofu, and some vegetable types. Analysis of specific risk factors and SNP analysis, combined, indicate that raw pork is a significant risk factor for exposure and infection to pathogenic YE cases, but not BT 1A cases., Competing Interests: The authors declare no conflict of interest.

Mainly performed within a rapid diagnostic tests company, a lateral flow (LF) system using gold nanoparticles (AuNPs) as transducers is presented able to detect three bacteria of interest, of relevance for antimicrobial resistance (AMR): Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), and Klebsiella pneumoniae, with a limit of detection of 25 ng/mL of glutamate dehydrogenase (GDH) for C. difficile, 36 ng/mL of penicillin-binding protein 2a (PBP2a) for MRSA, and 4 × 10 6  CFU/mL for K. pneumoniae. The system showed good results with bacteria culture samples, is user-friendly, and suitable for rapid testing, as the results are obtained within 15 min., (© 2024. The Author(s).)

While NLRP3 contributes to kidney fibrosis, the function of most NOD-like receptors (NLRs) in chronic kidney disease (CKD) remains unexplored. To identify further NLR members involved in the pathogenesis of CKD, we searched for NLR genes expressed by normal kidneys and differentially expressed in human CKD transcriptomics databases. For NLRP6, lower kidney expression correlated with decreasing glomerular filtration rate. The role and molecular mechanisms of Nlrp6 in kidney fibrosis were explored in wild-type and Nlrp6-deficient mice and cell cultures. Data mining of single-cell transcriptomics databases identified proximal tubular cells as the main site of Nlrp6 expression in normal human kidneys and tubular cell Nlrp6 was lost in CKD. We confirmed kidney Nlrp6 downregulation following murine unilateral ureteral obstruction. Nlrp6-deficient mice had higher kidney p38 MAPK activation and more severe kidney inflammation and fibrosis. Similar results were obtained in adenine-induced kidney fibrosis. Mechanistically, profibrotic cytokines transforming growth factor beta 1 (TGF-β1) and TWEAK decreased Nlrp6 expression in cultured tubular cells, and Nlrp6 downregulation resulted in increased TGF-β1 and CTGF expression through p38 MAPK activation, as well as in downregulation of the antifibrotic factor Klotho, suggesting that loss of Nlrp6 promotes maladaptive tubular cell responses. The pattern of gene expression following Nlrp6 targeting in cultured proximal tubular cells was consistent with maladaptive transitions for proximal tubular cells described in single-cell transcriptomics datasets. In conclusion, endogenous constitutive Nlrp6 dampens sterile kidney inflammation and fibrosis. Loss of Nlrp6 expression by tubular cells may contribute to CKD progression., (© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.)

Purpose: Lenalidomide remains an effective drug for multiple myeloma, but it is often associated with adverse events and requires dose adjustments. The objective of this study was to propose a model for predicting whether a patient would require dose adjustment., Methods: This retrospective observational study included patients treated with lenalidomide and dexamethasone from June 2014 to September 2018 at a tertiary hospital. Demographic variables, patient functional status, disease, analytical data specific to myeloma, and treatment-related variables were collected. Univariate and machine learning (logistic regression and classification and regression trees model) analyses were also performed. Kaplan-Meier analysis was used to determine the time of toxicity onset. Only lenalidomide (and not dexamethasone) related dose reductions are included., Results: A total of 64 patients received lenalidomide-dexamethasone. 69% (44) required dose reduction or discontinuation of treatment due to lenalidomide-related adverse events. The median time between treatment beginning and lenalidomide dose reduction or discontinuation was 8.0 months (95% CI: 6.0-17.0). Age, platelet count, and neutrophil count were related to dose reduction in the univariate model. In the multivariate models, age and neutrophil count were significant in the logistic regression model, renal clearance, and neutrophil count in the classification and regression trees model., Conclusion: Elderly patients and those with low bone marrow reserves are prone to dose-limiting adverse events. This study can aid in making follow-up, prophylaxis, and dosing decisions to achieve better pharmacotherapeutic results., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The mechanistic target of rapamycin complex 1 controls cellular anabolism in response to growth factor signaling and to nutrient sufficiency signaled through the Rag GTPases. Inhibition of mTOR reproducibly extends longevity across eukaryotes. Here we report that mice that endogenously express active mutant variants of RagC exhibit multiple features of parenchymal damage that include senescence, expression of inflammatory molecules, increased myeloid inflammation with extensive features of inflammaging and a ~30% reduction in lifespan. Through bone marrow transplantation experiments, we show that myeloid cells are abnormally activated by signals emanating from dysfunctional RagC-mutant parenchyma, causing neutrophil extravasation that inflicts additional inflammatory damage. Therapeutic suppression of myeloid inflammation in aged RagC-mutant mice attenuates parenchymal damage and extends survival. Together, our findings link mildly increased nutrient signaling to limited lifespan in mammals, and support a two-component process of parenchymal damage and myeloid inflammation that together precipitate a time-dependent organ deterioration that limits longevity., (© 2024. The Author(s).)

Enzyme-linked immunosorbent assay (ELISA) is the gold standard technique for measuring protein biomarkers due to its high sensitivity, specificity, and throughput. Despite its success, continuous advancements in ELISA and immunoassay formats are crucial to meet evolving global challenges and to address new analytical needs in diverse applications. To expand the capabilities and applications of immunoassays, we introduce a novel ELISA-like assay that we call Bioluminescent-bacteria-linked immunosorbent assay (BBLISA). BBLISA is an enzyme-free assay that utilizes the inner filter effect between the bioluminescent bacteria Allivibrio fischeri and metallic nanoparticles (gold nanoparticles and gold iridium oxide nanoflowers) as molecular absorbers. Functionalizing these nanoparticles with antibodies induces their accumulation in wells upon binding to molecular targets, forming the classical immune-sandwich complex. Thanks to their ability to adsorb the light emitted by the bacteria, the nanoparticles can suppress the bioluminescence signal, allowing the rapid quantification of the target. To demonstrate the bioanalytical properties of the novel immunoassay platform, as a proof of principle, we detected two clinically relevant biomarkers (human immunoglobulin G and SARS-CoV-2 nucleoprotein) in human serum, achieving the same sensitivity and precision as the classic ELISA. We believe that BBLISA can be a promising alternative to the standard ELISA techniques, offering potential advancements in biomarker detection and analysis by combining nanomaterials with a low-cost, portable bioluminescent platform.

Background: PolyDeep is a computer-aided detection and classification (CADe/x) system trained to detect and classify polyps. During colonoscopy, CADe/x systems help endoscopists to predict the histology of colonic lesions., Objective: To compare the diagnostic performance of PolyDeep and expert endoscopists for the optical diagnosis of colorectal polyps on still images., Methods: PolyDeep Image Classification (PIC) is an in vitro diagnostic test study. The PIC database contains NBI images of 491 colorectal polyps with histological diagnosis. We evaluated the diagnostic performance of PolyDeep and four expert endoscopists for neoplasia (adenoma, sessile serrated lesion, traditional serrated adenoma) and adenoma characterization and compared them with the McNemar test. Receiver operating characteristic curves were constructed to assess the overall discriminatory ability, comparing the area under the curve of endoscopists and PolyDeep with the chi- square homogeneity areas test., Results: The diagnostic performance of the endoscopists and PolyDeep in the characterization of neoplasia is similar in terms of sensitivity (PolyDeep: 89.05%; E1: 91.23%, p=0.5; E2: 96.11%, p<0.001; E3: 86.65%, p=0.3; E4: 91.26% p=0.3) and specificity (PolyDeep: 35.53%; E1: 33.80%, p=0.8; E2: 34.72%, p=1; E3: 39.24%, p=0.8; E4: 46.84%, p=0.2). The overall discriminative ability also showed no statistically significant differences (PolyDeep: 0.623; E1: 0.625, p=0.8; E2: 0.654, p=0.2; E3: 0.629, p=0.9; E4: 0.690, p=0.09). In the optical diagnosis of adenomatous polyps, we found that PolyDeep had a significantly higher sensitivity and a significantly lower specificity. The overall discriminative ability of adenomatous lesions by expert endoscopists is significantly higher than PolyDeep (PolyDeep: 0.582; E1: 0.685, p < 0.001; E2: 0.677, p < 0.0001; E3: 0.658, p < 0.01; E4: 0.694, p < 0.0001)., Conclusion: PolyDeep and endoscopists have similar diagnostic performance in the optical diagnosis of neoplastic lesions. However, endoscopists have a better global discriminatory ability than PolyDeep in the optical diagnosis of adenomatous polyps., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Davila-Piñón, Nogueira-Rodríguez, Díez-Martín, Codesido, Herrero, Puga, Rivas, Sánchez, Fdez-Riverola, Glez-Peña, Reboiro-Jato, López-Fernández and Cubiella.)

Diagnostic laboratories in Aotearoa, New Zealand (NZ) refer cultures from faecal samples positive for Shiga toxin genes to the national Enteric Reference Laboratory for isolation of Shiga toxin-producing Escherichia coli (STEC) for epidemiological typing. As there was variation in the culture media being referred, a panel of 75 clinical isolates of STEC, representing 28 different serotypes, was used to assess six commercially available media and provide guidance to clinical laboratories. Recommendations were subsequently tested for a 3-month period, where STEC isolations and confirmations were assessed by whole genome sequencing analysis against the culture media referred. CHROMagar™ STEC (CH-STEC; CHROMagar Microbiology, Paris, France) or CH-STEC plus cefixime-tellurite sorbitol MacConkey agar was confirmed inferior to CH-STEC plus blood agar with vancomycin, cefsulodin, and cefixime (BVCC). The former resulted in fewer STEC types (n = 18) being confirmed compared to those from a combination of CH-STEC and BVCC (n = 42). A significant (P < .05) association with an STEC's ability to grow on CH-STEC and the presence of the ter gene cluster, and eae was observed. Culturing screen positive STEC samples onto both CH-STEC and BVCC ensures a consistently higher recovery of STEC from all clinical samples in NZ than CH-STEC alone., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional "gold standard" biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

The metabolic functions of the liver are spatially organized in a phenomenon called zonation, linked to the differential exposure of portal and central hepatocytes to nutrient-rich blood. The mTORC1 signaling pathway controls cellular metabolism in response to nutrients and insulin fluctuations. Here we show that simultaneous genetic activation of nutrient and hormone signaling to mTORC1 in hepatocytes results in impaired establishment of postnatal metabolic and zonal identity of hepatocytes. Mutant hepatocytes fail to upregulate postnatally the expression of Frizzled receptors 1 and 8, and show reduced Wnt/β-catenin activation. This defect, alongside diminished paracrine Wnt2 ligand expression by endothelial cells, underlies impaired postnatal maturation. Impaired zonation is recapitulated in a model of constant supply of nutrients by parenteral nutrition to piglets. Our work shows the role of hepatocyte sensing of fluctuations in nutrients and hormones for triggering a latent metabolic zonation program., (© 2024. The Author(s).)

The problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and the high cost of some formulations, call for the urgent identification of new therapeutic agents with novel modes of action. The aggregated protein dye YAT2150 has been found to be a potent antileishmanial compound, with a half-maximal inhibitory concentration (IC 50 ) of approximately 0.5 µM against promastigote and amastigote stages of Leishmania infantum . The encapsulation in liposomes of YAT2150 significantly improved its in vitro IC 50 to 0.37 and 0.19 µM in promastigotes and amastigotes, respectively, and increased the half-maximal cytotoxic concentration in human umbilical vein endothelial cells to >50 µM. YAT2150 became strongly fluorescent when binding intracellular protein deposits in Leishmania cells. This fluorescence pattern aligns with the proposed mode of action of this drug in the malaria parasite Plasmodium falciparum , the inhibition of protein aggregation. In Leishmania major , YAT2150 rapidly reduced ATP levels, suggesting an alternative antileishmanial mechanism. To the best of our knowledge, this first-in-class compound is the only one described so far having significant activity against both Plasmodium and Leishmania , thus being a potential drug for the treatment of co-infections of both parasites., Competing Interests: A patent application (priority number: EP21382949.2; application number: PCT/EP2022/079438; application date: 21/10/2022) has been filed to protect some of the results presented in the paper, which includes as inventors IB-A, EMA, DM-T and XF-B. All other authors declare they have no competing interests.

California is home to a multibillion-dollar cannabis (marijuana) industry, but little is known about the occupational health and safety hazards faced by cannabis workers and even less of the stress, mental health, and coping mechanisms among these workers. Previous research has been based on long-term workers at legal businesses, but most California cannabis is produced and sold unlawfully. There are many seasonal workers whose experiences have not been studied. A qualitative study based on focus group discussions and key informant interviews was performed to understand cannabis workers' experiences, knowledge, and perceptions of occupational hazards. Participants reported sources of stress including production pressure and isolation, and mental health outcomes such as depression and mental fatigue. They described primarily maladaptive coping mechanisms. Unique characteristics of the cannabis industry, including criminalization and isolated, remote farms, make interventions challenging. However, policy approaches that involve community organizations could promote worker health., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Study Aims: The single-operator cholangiopancreatoscopy (SOCP) with the SpyGlass™ system is a endoscopy technique whose use has grown exponentially in recent years. The aims of this study were to evaluate the efficacy and safety of SOCP with SpyGlass™ and determine the factors related to the onset of adverse events (AEs)., Patients and Methods: Retrospective study at a single tertiary institution with inclusion of all consecutive patients undergoing SOCP with SpyGlass™ from February-2009 to December-2021. No exclusion criteria were considered. A descriptive statistical analysis was performed. The factors associated with the existence of AE were analyzed using Chi-square and Student's t-test., Results: A total of 95 cases were included. The most common indications were biliary strictures (BS) evaluation (66.3%) or treatment of difficult common bile duct stones (27.4%). Technical and clinical success was attained in 98.9%. Single-session stone clearance was obtained in 84%. The AE rate was 7.4%. To detect malignancy in BS, optical diagnosis presents a sensitivity and specificity of 100% and 91.2%, respectively; while histology results were 36.4% and 100% respectively. A previous endoscopic sphincterotomy was associated with a lower rate of AEs (2.4% vs 41.7%; p<0.001)., Conclusions: SOCP with SpyGlass™ is a safe and effective technique to diagnose and treat pancreatobiliary pathology. The presence of sphincterotomy performed prior to the procedure could improve the technique's safety., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Planar cell polarity (PCP) proteins coordinate tissue morphogenesis by governing cell patterning and polarity. Asymmetrically localized on the plasma membrane of cells, transmembrane PCP proteins are trafficked by endocytosis, suggesting they may have intracellular functions that are dependent or independent of their extracellular role, but whether these functions extend to transcriptional control remains unknown. Here, we show the nuclear localization of transmembrane, PCP protein, VANGL2, in the HCC1569 breast cancer cell line, and in undifferentiated, but not differentiated, HC11 cells that serve as a model for mammary lactogenic differentiation. The loss of Vangl2 function results in upregulation of pathways related to STAT5 signaling. We identify DNA binding sites and a nuclear localization signal in VANGL2, and use CUT&RUN to demonstrate recruitment of VANGL2 to specific DNA binding motifs, including one in the Stat5a promoter. Knockdown (KD) of Vangl2 in HC11 cells and primary mammary organoids results in upregulation of Stat5a , Ccnd1 and Csn2 , larger acini and organoids, and precocious differentiation; phenotypes are rescued by overexpression of Vangl2 , but not Vangl2 Δ NLS . Together, these results advance a paradigm whereby PCP proteins coordinate tissue morphogenesis by keeping transcriptional programs governing differentiation in check.

Competing Interests: Conflict of interest The authors whose names are listed in the manuscript have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.

Background: Pru p 7 has been reported as a major allergen in peach allergy, associated with severe clinical symptoms and related to IgE sensitisation to cypress pollen. The main objective of this study was to prospectively evaluate the frequency of sensitisation to Pru p 7 and its clinical relevance amongst pediatric patients with peach allergy in Madrid (Spain)., Methods: Patients with a history of IgE-mediated symptoms (oral allergy syndrome, urticaria/angioedema, rhinoconjunctivitis/asthma, gastrointestinal symptoms, or anaphylaxis) occurring within 2 h after peach intake or contact were prospectively recruited from February 2020 to September 2021. Skin tests, sIgE by ImmunoCAP® (Pru p 1, Pru p 3, Pru p 4, Pru p 7, and Cupressus arizonica) and oral food challenge (OFC) were performed. The study was approved by the local Ethics Committee (PI-4513)., Results: Ninety-two patients were included (53.3% male); median age, 10 (IQR 6.0-14.75) years. Seventy-four (80.4%) patients had a reaction after ingestion of fresh peach (25.0% from peel, 23.9% from pulp, and 44.6% from both). Fifteen (16.3%) patients were sensitised to Pru p 7. Upper airway symptoms, anaphylaxis, and grade 2 reactions were statistically more frequent in patients sensitised to Pru p 7. Seven (7.9%) patients presented with exercise as a cofactor, four of whom were sensitised to Pru p 7 (p = .001). Patients sensitised to Pru p 7 were significantly more likely to have a positive OFC result than patients who were not (p = .008). Four patients who reacted to peach at OFC were sensitised to Pru p 7. Specific IgE against Cupressus arizonica pollen was positive in 25 (62.5%) patients., Conclusions: Pru p 7 sensitisation was observed in 16.3% of our population and was related to severe reactions, upper airway symptoms, anaphylaxis, and the presence of an eliciting cofactor., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objectives: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli) are a main cause of human deaths associated with antimicrobial resistance (AMR). Despite hundreds of reports of the faecal carriage of ESBL-E. coli in domestic and wild animals, the dynamics of its circulation remains poorly understood., Methods: We used whole genome sequencing of 19 ESBL-E. coli previously isolated in the same local setting from dogs, livestock, and a wild rodent in Central Chile to assess potential cross-species transmission of ESBL-E. coli., Results: Isolates harboured a large number of AMR (n = 95) and virulence (n = 45) genes, plasmids replicons (n = 24), and E. coli sequence types including top extraintestinal pathogenic E. coli ST410, ST58, ST88, and ST617. Almost identical clones (<50 single nucleotide polymorphisms difference, same antibiotic and heavy metal resistance genes, virulence genes, and plasmids) were found in faeces of dogs, cattle, or sheep from the same farm, and in a dog and a wild rodent living in proximity., Conclusions: To our knowledge, this is the first report of multiple clonal cross-species transmission of ESBL-E. coli in domestic and potentially wild animals of Latin America. Our results suggest that relatively rare spread of AMR across animal species can still occur by both clonal and plasmid dissemination. Our study highlights the need for establishing preventive measures to limit the circulation of these bacteria among animals in agricultural settings, particularly given the highly pathogenic profile of several E. coli strains detected in these animals., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

(1) Background: COVID-19 has evolved during seven epidemic waves in Spain. Our objective was to describe changes in mortality and severity in our hospitalized patients. (2) Method: This study employed a descriptive, retrospective approach for COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) until 31 December 2022. (3) Results: A total of 5510 admissions for COVID-19 were recorded. The first wave accounted for 1823 (33%) admissions and exhibited the highest proportion of severe patients: 65% with bilateral pneumonia and 83% with oxygen saturation under 94% during admission and elevated levels of CRP, IL-6, and D-dimer. In contrast, the seventh wave had the highest median age (79 years) and comorbidity (Charlson: 2.7), while only 3% of patients had bilateral pneumonia and 3% required intubation. The overall mortality rate was 10.3%. The first wave represented 39% of the total. The variables related to mortality were age (OR: 1.08, 1.07-1.09), cancer (OR: 1.99, 1.53-2.60), dementia (OR: 1.82, 1.20-2.75), the Charlson index (1.38, 1.31-1.47), the need for high-flow oxygen (OR: 6.10, 4.94-7.52), mechanical ventilation (OR: 11.554, 6.996-19.080), and CRP (OR: 1.04, 1.03-1.06). (4) Conclusions: The variables associated with mortality included age, comorbidity, respiratory failure, and inflammation. Differences in the baseline characteristics of admitted patients explained the differences in mortality in each wave. Differences observed between patients admitted in the latest wave and the earlier ones suggest that COVID-19 has evolved into a distinct disease, requiring a distinct approach.

The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas. The Chilean-Cordobes clone (ChC) (ST5-SCC mec I) has been the predominant MRSA clone in Chile since its first description in 1998, despite the report of other emerging MRSA clones in recent years. Here, we characterize the evolutionary history of MRSA from 2000 to 2016 in a Chilean tertiary health care center using phylogenomic analyses. We sequenced 469 MRSA isolates collected between 2000 and 2016. We evaluated the temporal trends of the circulating clones and performed a phylogenomic reconstruction to characterize the clonal dynamics. We found a significant increase in the diversity and richness of sequence types (STs; Spearman r  = 0.8748, P  < 0.0001) with a Shannon diversity index increasing from 0.221 in the year 2000 to 1.33 in 2016, and an effective diversity (Hill number; q = 2) increasing from 1.12 to 2.71. The temporal trend analysis revealed that in the period 2000 to 2003 most of the isolates (94.2%; n  = 98) belonged to the ChC clone. However, since then, the frequency of the ChC clone has decreased over time, accounting for 52% of the collection in the 2013 to 2016 period. This decline was accompanied by the rise of two emerging MRSA lineages, ST105-SCC mec II and ST72-SCC mec VI. In conclusion, the ChC clone remains the most frequent MRSA lineage, but this lineage is gradually being replaced by several emerging clones, the most important of which is clone ST105-SCC mec II. To the best of our knowledge, this is the largest study of MRSA clonal dynamics performed in South America. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape. We used whole-genome sequencing to study 469 MRSA isolates collected between 2000 and 2016 in Chile providing the largest and most detailed study of clonal dynamics of MRSA in South America to date. We found a significant increase in the diversity of MRSA clones circulating over the 17-year study period. Additionally, we describe the emergence of two novel clones (ST105-SCC mec II and ST72-SCC mec VI), which have been gradually increasing in frequency over time. Our results drastically improve our understanding of the dissemination and update our knowledge about MRSA in Latin America., Competing Interests: The authors declare no conflict of interest.

Background: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care., Methods: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum β-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period., Results: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .001) for broad-spectrum β-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre-COVID-19 to 51.9% after pandemic onset (P < .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC., Conclusions: AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts., Competing Interests: Potential conflicts of interest. R. A. reports funding from the US Centers for Disease Control and Prevention, the China Center for Disease Control, and the Chile Ministry of Science (ANID). They report receiving consulting fees for COVID-19 vaccines from AstraZeneca, Pfizer, and Sinovac; attending the Tecnofarma meeting on COVID-19 vaccines; and holding a leadership position with the COVID-19 external advisory group to the Chile Ministry of Health. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic., Methods: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive., Results: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively., Conclusions: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals., Competing Interests: Potential conflicts of interest. Rafael Araos reports funding from the US Centers for Disease Control and Prevention (CDC), China Center for Disease Control, and the Chile Ministry of Science (ANID). He reports consulting for coronavirus disease 2019 (COVID-19) vaccines from Astra Zeneca, Pfizer, and Sinovac; support for attending a meeting about COVID-19 vaccines from Tecnofarma, and helds a position with the COVID-19 external advisory group to the Chile Ministry of Health. Erika MC D'Agata reports receiving a grant for optimizing antimicrobial use in dialysis units (AHRQ R01). José M. Munita reports receiving funding from CDC Broad Agency Announcements (BAA) (FY2018-OADS-01). Dino Sepúlveda reports research funding from the Canadian Institutes of Health (Grant 136927) and The Universidad del Desarrollo, and also reports honoraria for lectures and teaching with the University of Santiago of Chile, Universidad Autonoma de Chile, and World Bank. He also received support for travel and accommodation for attending the LATAM policy forum and an international workshop on HTA. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: This study aimed to compare ramucirumab-paclitaxel versus chemotherapy in second-line (2L) advanced gastroesophageal cancer (aGEC) based on HER2 status and analyze prognostic factors., Methods: The study includes patients from the AGAMENON-SEOM registry with aGEC and known HER2 status who received 2L between 2016 and 2021. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) and multivariable Cox regression analysis was done to adjust for confounding variables., Results: Of the 552 patients who met the selection criteria, 149 (26.9%) had HER2-positive aGEC, 89 were treated with chemotherapy, and 60 with ramucirumab-paclitaxel, and 403 had an HER2-negative aGEC, 259 were treated with chemotherapy, and 144 with ramucirumab-paclitaxel. In the whole sample, 2L PFS was 3.0 months (95% CI 2.8-3.2), 2L OS, 5.7 months (5.2-6.3), and ramucirumab-paclitaxel versus chemotherapy was associated with increased PFS (HR 0.64, 95% CI 0.53-0.78, p < 0.0001) and OS (HR 0.68, 0.55-0.83, p = 0.0002). Median PFS of ramucirumab- paclitaxel versus chemotherapy was 3.5 vs 2.8 months (HR 0.67, 0.54-0.83, p = 0.0004) in HER2-negative, and 4.7 vs 2.7 months (HR 0.57, 0.40-0.82, p = 0.0031) in HER2-positive aGEC, respectively. Median OS for ramucirumab-paclitaxel versus chemotherapy was 6.6 vs 5 months (HR 0.67, 0.53-0.85, p = 0.0007) in HER2-negative, and 7.4 vs 5.6 months (HR 0.70, 0.53-1.04, p = 0.083) in HER2-positive aGEC, respectively. ECOG-PS, tumor burden, Lauren subtype, and neutrophil-lymphocyte ratio were prognostic factors., Conclusions: In patients with an aGEC from the AGAMENON-SEOM registry, 2L treatment with ramucirumab-paclitaxel was superior to chemotherapy in PFS, OS and response rate, independent of HER2 status., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The adhesion of initial colonizers such as Streptococcus mutans to collagen is critical for dentinal and root caries progression. One of the most described pathological and aging-associated changes in collagen-including dentinal collagen-is the generation of advanced glycation end-products (AGEs) such as methylglyoxal (MGO)-derived AGEs. Despite previous reports suggesting that AGEs alter bacterial adhesion to collagen, the biophysics driving oral streptococcal attachment to MGO-modified collagen remains largely understudied. Thus, the aim of this work was to unravel the dynamics of the initial adhesion of S. mutans to type I collagen in the presence and absence of MGO-derived AGEs by employing bacterial cell force spectroscopy with atomic force microscopy (AFM). Type I collagen gels were treated with 10 mM MGO to induce AGE formation, which was characterized with microscopy and enzyme-linked immunosorbent assay. Subsequently, AFM cantilevers were functionalized with living S. mutans UA 159 or Streptococcus sanguinis SK 36 cells and probed against collagen surfaces to obtain force curves displaying bacterial attachment in real time, from which the adhesion force, number of events, Poisson analysis, and contour and rupture lengths for each individual detachment event were computed. Furthermore, in silico computer simulation docking studies between the relevant S. mutans UA 159 collagen-binding protein SpaP and collagen were computed, in the presence and absence of MGO. Overall, results showed that MGO modification increased both the number and adhesion force of single-unbinding events between S. mutans and collagen, without altering the contour or rupture lengths. Both experimental and in silico simulations suggest that this effect is due to increased specific and nonspecific forces and interactions between S. mutans UA 159 and MGO-modified collagen substrates. In summary, these results suggest that collagen alterations due to aging and glycation may play a role in early bacterial adherence to oral tissues, associated with conditions such as aging or chronic hyperglycemia, among others.

Background/aim: The aim of the study is to describe the efficacy and to determine the functional outcome in terms of visual acuity and refractive defect of a single dose of intravitreal bevacizumab in patients with high-risk ROP type 1., Methods: In this retrospective clinical study patients diagnosed between December 2013 and January 2018 with high-risk pre-threshold ROP type 1 and treated with intravitreal bevacizumab were selected. All patients were treated following the established protocol at our centre. Those patients with less than three-year follow-up were excluded. Visual acuity and cycloplegic refraction in the last visit were registered. Treatment efficacy was defined as the absence of retreatment with intravitreal anti-VEGF or laser during follow-up., Results: A total of 38 infants (76 eyes) were included in the analysis. Twenty infants (40 eyes) completed visual acuity testing. Mean age was 6 years (IQR: 4-9). Median visual acuity was 0.8 (IQR: 0.5-1). Thirty-four eyes (85%) had good visual acuity (greater than or equal to 0.5). Thirty-seven patients (74 eyes) had cycloplegic refraction measured. Median spherical equivalent at the last visit was +0.94 (IQR: -0.25; 1.88). Treatment success rate was 96.05%., Conclusion: Intravitreal bevacizumab treatment showed good functional outcome in patients with high-risk ROP type 1. In our study, good response to treatment was observed with a success rate over 95%., (Copyright © 2023 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: The epidemiology of respiratory syncytial virus (RSV) infection has changed during the COVID-19 pandemic. Our objectives were to describe the RSV epidemic in 2021 and compare it with the previous years to the pandemic., Methods: Retrospective study performed in Madrid (Spain) in a large pediatric hospital comparing the epidemiology and clinical data of RSV admissions during 2021 and the two previous seasons., Results: 899 children were admitted for RSV infection during the study period. During 2021, the outbreak peaked in June and the last cases were identified in July. Previous seasons were detected in autumn-winter. The number of admissions in 2021 was significantly lower than in previous seasons. There were no differences between seasons regarding age, sex or disease severity., Conclusion: RSV hospitalizations during 2021 in Spain moved to summer with no cases in autumn and winter 2020-2021. Unlike other countries, clinical data were similar between epidemics., (© 2021 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

The second-line antileishmanial compound pentamidine is administered intramuscularly or, preferably, by intravenous infusion, with its use limited by severe adverse effects, including diabetes, severe hypoglycemia, myocarditis and renal toxicity. We sought to test the potential of phospholipid vesicles to improve the patient compliance and efficacy of this drug for the treatment of leishmaniasis by means of aerosol therapy. The targeting to macrophages of pentamidine-loaded liposomes coated with chondroitin sulfate or heparin increased about twofold (up to ca. 90%) relative to noncoated liposomes. The encapsulation of pentamidine in liposomes ameliorated its activity on the amastigote and promastigote forms of Leishmania infantum and Leishmania pifanoi , and it significantly reduced cytotoxicity on human umbilical endothelial cells, for which the concentration inhibiting 50% of cell viability was 144.2 ± 12.7 µM for pentamidine-containing heparin-coated liposomes vs. 59.3 ± 4.9 µM for free pentamidine. The deposition of liposome dispersions after nebulization was evaluated with the Next Generation Impactor, which mimics human airways. Approximately 53% of total initial pentamidine in solution reached the deeper stages of the impactor, with a median aerodynamic diameter of ~2.8 µm, supporting a partial deposition on the lung alveoli. Upon loading pentamidine in phospholipid vesicles, its deposition in the deeper stages significantly increased up to ~68%, and the median aerodynamic diameter decreased to a range between 1.4 and 1.8 µm, suggesting a better aptitude to reach the deeper lung airways in higher amounts. In all, nebulization of liposome-encapsulated pentamidine improved the bioavailability of this neglected drug by a patient-friendly delivery route amenable to self-administration, paving the way for the treatment of leishmaniasis and other infections where pentamidine is active.

Background/aim: This study aimed to assess the effectiveness and safety of nivolumab versus cetuximab in patients with Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M HNSCC), as well as to analyze possible prognostic factors for response to treatment with nivolumab., Patients and Methods: We conducted an observational, retrospective, descriptive study of patients with R/M HNSCC who initiated treatment with nivolumab or cetuximab monotherapy in two periods of equivalent duration. Overall efficacy was measured in terms of progression-free survival (PFS) and overall survival (OS). Safety was evaluated using the Common Terminology Criteria for Adverse Events classification version 5.0 of the National Cancer Institute., Results: Median OS was 9.1 months with nivolumab (n=34) and 6.3 months with cetuximab (n=12). PFS was 4.3 months for nivolumab and 4.65 months for cetuximab. Any grade adverse events (AEs) were reported in 97% and 100% of the patients treated with nivolumab and cetuximab. Serious AEs were observed in 26% and 58% of the patients, respectively. Elevated albumin values, lymphocytosis, neutropenia, and elevated neutrophil/lymphocyte ratio values were found to have positive prognostic value on the response to nivolumab in R/M HNSCC., Conclusion: Effectiveness of nivolumab in terms of OS remains superior to cetuximab. OS, PFS and severe or any grade AEs were superior in both arms of our study compared to those in clinical trials. The AEs profile of nivolumab differed in our study from that in the clinical trials' observations. We have identified four statistically significant prognostic variables on the response to nivolumab in R/M HNSCC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab., Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included. The model was externally validated in an independent series (The Christie NHS Foundation Trust, Manchester, UK)., Results: In all, 737 patients were recruited (AGAMENON-SEOM, n  = 654; Manchester, n  = 83). Median PFS and OS in the training cohort were 7.76 [95% confidence interval (CI), 7.13-8.25] and 14.0 months (95% CI, 13.0-14.9), respectively. Six covariates were significantly associated with OS: neutrophil-to-lymphocyte ratio, Eastern Cooperative Oncology Group performance status, Lauren subtype, HER2 expression, histological grade and tumour burden. The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for corrected PFS/OS of 0.606 (95% CI, 0.578-0.636) and 0.623 (95% CI, 0.594-0.655), respectively. In the validation cohort, the model is well calibrated, with a c-index of 0.650 and 0.683 for PFS and OS, respectively., Conclusion: The AGAMENON-HER2 prognostic tool stratifies HER2-positive AGA patients receiving trastuzumab and chemotherapy according to their estimated survival endpoints., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Entomopathogenic fungi, widely available biological agents used to control agricultural pests, are sporadically reported to cause focal or disseminated infection in reptiles and mammals, including humans. This study summarizes the clinical presentation, histopathological and molecular findings by panfungal polymerase chain reaction and sequencing of four cases of hypocrealean fungal infections in captive common green iguanas (Iguana, iguana). One case of granulomatous pneumonia, hepatitis and serositis was related to Metarhizium flavoviride complex infection. Two disseminated fungal infection cases, with scarce inflammatory cell infiltration, were caused by Beauveria bassiana while there was one case of multifocal granulomatous and necrotizing pneumonia by Purpureocillium spp. To the best of our knowledge, this is the first report of fatal mycosis infection due to entomopathogenic fungi in captive common green iguanas., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Cannabis is a multi-billion-dollar California industry, but little is known about the occupational hazards or health experiences of cannabis cultivation workers. Respiratory and dermal exposures, musculoskeletal hazards, and other agricultural hazards have been identified in previous research. Even in a post-legalization framework, cannabis work is stigmatized and most cannabis is still produced illegally. Qualitative research is essential for establishing rapport with cannabis workers to understand their experiences and concerns., Methods: We conducted semi-structured discussions with four focus groups including 32 cannabis workers total, and 9 key informants who were workers, industry experts, and business owners or managers. Transcribed results were analyzed to identify key themes on physiological exposures and health effects., Results: The majority (81.3%) of focus group participants were seasonal migrant cannabis trimmers. Themes emerged of respiratory and dermal exposures and outcomes, musculoskeletal disorders, and physical hazards including living conditions. Workers reported respiratory symptoms and rashes from exposure to cannabis, mold, and pesticides. Musculoskeletal pain was ubiquitous due to inadequate seating and long shifts performing repetitive tasks. Seasonal workers experienced chronic exposure to cold conditions and unsanitary housing. Management-level interviewees and other industry stakeholders described concerns and experiences that differed from those of workers., Discussion: The results were consistent with existing research on cannabis worker health, with workers reporting respiratory and dermal exposure and symptoms, musculoskeletal hazards, and physical hazards associated with agricultural work. In addition, we found that workers were affected by substandard living conditions, remote and isolated work environments, and an absence of training., (© 2022 Wiley Periodicals LLC.)

Background: Metastatic breast cancer (MBC) is incurable. Systemic therapy is the standard treatment; however, an optimal sequence of chemotherapy has not been established., Objective: Evaluating effectiveness and safety of eribulin in MBC treatment and comparing the results obtained with published literature., Methods: Observational, descriptive and retrospective study of patients with MBC treated with eribulin from 01/12/2015 to 30/10/2021. Effectiveness was analysed using Kaplan-Meier-survival-curves, for the overall number of patients treated and stratified by treatment line. Safety was measured according to adverse events (AE) based on CTCAE v5.0. Data analysis was performed using R v4.0.1., Results: They were included in this study 53 women who received eribulin (median age 58 years). Comparison of median survival from this study versus published data were: progression-free-survival (PFS) 3 (IC95%: 3-4) versus 3.7 months and overall-survival (OS) 8 (IC95%: 3-4) versus 13.2 months for the overall number of patients. For the 1-3 line treatment group, PFS was 6 (IC95%: 3-NA) and OS was 15 (IC95%: 6-NA). There were 322 AEs, the most frequent being blood disorders 16% (52), general disorders 12% (38), and gastrointestinal disorders 12% (38)., Conclusions: The median PFS was similar to that reported previously, with lower OS. There was a tendency to achieve better results when eribulin was used earlier. Eribulin is a less well-tolerated drug than published literature.

Human papillomavirus 31 (HPV31) is the fourth most frequent high-risk HPV (HR-HPV) genotype identified in cervical cancer (CC) worldwide and in Mexico. It has been recently classified into three lineages (A, B, and C) and eight sublineages (A1, A2, B1, B2, and C1 - C4). Here, we report the complete genomic sequences of 14 HPV31 isolates from cervical samples, and these were compared with viral genome sequences from the GenBank database for phylogenetic and genetic distance analysis. The formation of two novel clades within the C lineage (proposed as C5 and C6) was observed, with a well-defined variant-specific mutational pattern. The smallest average pairwise distance was 0.71% for lineages A and B, 0.94% for lineages A and C, and 1.01% for lineages B and C, and between sublineages, these values were 0.21% for clade A, 0.29% for clade B, and 0.24% for clade C. The isolates were grouped into the sublineages A1, B2, C1-C3, and C6. This is the first report on the whole-genome diversity of HPV31 in Mexico., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: The COVID-19 pandemic was declared on March 11 th , 2020. By the end of January, the first imported cases were detected in Spain and, by March, the number of cases was growing exponentially, causing the implementation of a national lockdown. Madrid has been one of the most affected regions in terms of both cases and deaths. The aim of this study is to describe the epidemic curve and the epidemiological features and outcomes of COVID-19 patients hospitalized in La Paz University Hospital, a tertiary hospital located in Madrid., Methods: We included confirmed and probable COVID-19 cases admitted to our centre from February 26 th to June 1 st , 2020. We studied trends in hospitalization and ICU admissions using joinpoint regression analysis., Results: A sample of 2970 patients was obtained. Median age was 70 years old (IQR 55-82) and 54.8% of them were male. ICU admission rate was 8.7% with a mortality rate of 45.7%. Global CFR was 21.8%. Median time from symptom onset to death was 14 days (IQR 9-22)., Conclusions: We detected an admissions peak on March 21st followed by a descending trend, matching national and regional data. Age and sex distribution were comparable to further series nationally and in western countries., (©2022 Pacini Editore SRL, Pisa, Italy.)

Background: SARS-CoV-2 infections have a wide spectrum of clinical manifestations whose causes are not completely understood. Some human conditions predispose to severe outcome, like old age or the presence of comorbidities, but many other facets, including coinfections with other viruses, remain poorly characterized., Methods: In this study, the eukaryotic fraction of the respiratory virome of 120 COVID-19 patients was characterized through whole metagenomic sequencing., Results: Genetic material from respiratory viruses was detected in 25% of all samples, whereas human viruses other than SARS-CoV-2 were found in 80% of them. Samples from hospitalized and deceased patients presented a higher prevalence of different viruses when compared to ambulatory individuals. Small circular DNA viruses from the Anneloviridae (Torque teno midi virus 8, TTV-like mini virus 19 and 26) and Cycloviridae families (Human associated cyclovirus 10), Human betaherpesvirus 6, were found to be significantly more abundant in samples from deceased and hospitalized patients compared to samples from ambulatory individuals. Similarly, Rotavirus A, Measles morbillivirus and Alphapapilomavirus 10 were significantly more prevalent in deceased patients compared to hospitalized and ambulatory individuals., Conclusions: Results show the suitability of using metagenomics to characterize a broader peripheric virological landscape of the eukaryotic virome in SARS-CoV-2 infected patients with distinct disease outcomes. Identified prevalent viruses in hospitalized and deceased patients may prove important for the targeted exploration of coinfections that may impact prognosis., (© 2022. The Author(s).)

Objectives: This study aimed to compare the characteristics of fully and partially vaccinated or unvaccinated coronavirus disease 2019 (COVID-19) patients who were hospitalised in a population of 220,000 habitants., Methods: Retrospective, observational, and population studies were conducted on patients who were hospitalised due to COVID-19 from March to October 2021. We assessed the impact of vaccination and other risk factors through Cox multivariate analysis., Results: A total of 500 patients were hospitalised, among whom 77 (15.4%) were fully vaccinated, 86 (17.2%) were partially vaccinated, and 337 (67.4%) were unvaccinated. Fully vaccinated (FV) patients were older and had a higher Charlson index than those of partially vaccinated and unvaccinated patients (NFV). Bilateral pneumonia was more frequent among NFV (259/376 (68.9%)) than among FV patients (32/75 (42.7%)). The former had more intensive care unit admissions (63/423) than the latter (4/77); OR: 2.80; CI (1.07-9.47). Increasing age HZ: 1.1 (1.06-1.14)) and haematological disease at admission HZ: 2.99 (1.26-7.11)) were independent risk factors for higher mortality during the first 30 days of hospitalisation. The probability of an earlier discharge in the subgroup of 440 patients who did not die during the first 30 days of hospitalisation was related to age (older to younger: HZ: 0.98 (0.97-0.99)) and vaccination status., Conclusions: Among the patients hospitalised because of COVID-19, complete vaccination was associated with less severe forms of COVID-19, with an earlier discharge date. Age and haematological disease were related to a higher mortality rate during the first 30 days of hospitalisation.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is one of the pathogens that urgently needs new drugs and new alternatives for its control. The primary strategy to combat this bacterium is combining treatments of beta-lactam with a beta-lactamase inhibitor. The most used combinations against P. aeruginosa are ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T). Although mechanisms leading to CZA and C/T resistance have already been described, among which are the resistance-nodulation-division (RND) efflux pumps, the role that these extrusion systems may play in CZA, and C/T baseline susceptibility of clinical isolates remains unknown. For this purpose, 161 isolates of non-carbapenemase-producing (Non-CP) CRPA were selected, and susceptibility tests to CZA and C/T were performed in the presence and absence of the RND efflux pumps inhibitor, Phenylalanine-arginine β-naphthylamide (PAβN). In the absence of PAβN, C/T showed markedly higher activity against Non-CP-CRPA isolates than observed for CZA. These results were even more evident in isolates classified as extremely-drug resistant (XDR) or with difficult-to-treat resistance (DTR), where CZA decreased its activity up to 55.2% and 20.0%, respectively, whereas C/T did it up to 82.8% (XDR), and 73.3% (DTR). The presence of PAβN showed an increase in both CZA (37.6%) and C/T (44.6%) activity, and 25.5% of Non-CP-CRPA isolates increased their susceptibility to these two combined antibiotics. However, statistical analysis showed that only the C/T susceptibility of Non-CP-CRPA isolates was significantly increased. Although the contribution of RND activity to CZA and C/T baseline susceptibility was generally low (two-fold decrease of minimal inhibitory concentrations [MIC]), a more evident contribution was observed in a non-minor proportion of the Non-CP-CRPA isolates affected by PAβN [CZA: 25.4% (15/59); C/T: 30% (21/70)]. These isolates presented significantly higher MIC values for C/T. Therefore, we conclude that RND efflux pumps are participating in the phenomenon of baseline susceptibility to CZA and, even more, to C/T. However, the genomic diversity of clinical isolates is so great that deeper analyzes are necessary to determine which elements are directly involved in this phenomenon., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Contreras-Gómez, Martinez, Rivas, Riquelme-Neira, Ugalde, Wozniak, García, Munita, Olivares-Pacheco and Alcalde-Rico.)