Anesthetic Management of a Patient With Trisomy 18 Undergoing a Multilevel Spinal Fusion.

Trisomy 18 is the second most common autosomal trisomy aside from trisomy 21. Anesthesiologists were unlikely to manage such patients in the past, specifically those surviving later into childhood due to the 90% mortality rate within the first year of life and the lack of procedural options that were available. However, a paucity of literature regarding the anesthetic management of such patients exists. Trisomy 18 patients present a unique anesthetic challenge, given the presence of associated dysmorphic facial features and the involvement of multiple organ systems, leading to difficult airway and hemodynamic disturbances. In this case report, we present the anesthetic management of a 9-year-old patient with trisomy 18 undergoing a multilevel spinal fusion. Despite significant intraoperative hemorrhage, the patient was able to tolerate the procedure without complications, likely owing to the meticulous preoperative preparation and the patient's survival later into childhood. This case contributes to a small subset of literature which suggests that patients with trisomy 18 who survive later into childhood have an improved ability to tolerate general anesthesia.

Association of CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T Polymorphisms with Tacrolimus Dose, Serum Concentration, and Biochemical Parameters in Mexican Patients with Kidney Transplant.

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.

The destructive subterranean termite Reticulitermes flavipes (Blattodea: Rhinotermitidae) can colonize arid territories.

Reticulitermes flavipes, one of the most destructive subterranean termite species, has been detected for the first time in an arid territory: Lanzarote (Canary Islands, Spain). This invasive species was introduced into several countries but never such a dry region. Although there are places with presence of this termite at similar or even higher temperatures, none has annual rainfall (10.1 mm) as low as Lanzarote. On this island it is present in semi-desert, near an affected urban area. Distribution, genetic, climate and host-plant data are evaluated to track and understand its invasion process in the archipelago.

The Cellular Abundance of Chemoreceptors, Chemosensory Signaling Proteins, Sensor Histidine Kinases, and Solute Binding Proteins of Pseudomonas aeruginosa Provides Insight into Sensory Preferences and Signaling Mechanisms.

Chemosensory pathways and two-component systems are important bacterial signal transduction systems. In the human pathogen Pseudomonas aeruginosa, these systems control many virulence traits. Previous studies showed that inorganic phosphate (Pi) deficiency induces virulence. We report here the abundance of chemosensory and two-component signaling proteins of P. aeruginosa grown in Pi deficient and sufficient media. The cellular abundance of chemoreceptors differed greatly, since a 2400-fold difference between the most and least abundant receptors was observed. For many chemoreceptors, their amount varied with the growth condition. The amount of chemoreceptors did not correlate with the magnitude of chemotaxis to their cognate chemoeffectors. Of the four chemosensory pathways, proteins of the Che chemotaxis pathway were most abundant and showed little variation in different growth conditions. The abundance of chemoreceptors and solute binding proteins indicates a sensing preference for amino acids and polyamines. There was an excess of response regulators over sensor histidine kinases in two-component systems. In contrast, ratios of the response regulators CheY and CheB to the histidine kinase CheA of the Che pathway were all below 1, indicative of different signaling mechanisms. This study will serve as a reference for exploring sensing preferences and signaling mechanisms of other bacteria.

The pH Robustness of Bacterial Sensing.

Bacteria have evolved many different signal transduction systems to sense and respond to changing environmental conditions. Signal integration is mainly achieved by signal recognition at extracytosolic ligand-binding domains (LBDs) of receptors. Hundreds of different LBDs have been reported, and our understanding of their sensing properties is growing. Receptors must function over a range of environmental pH values, but there is little information available on the robustness of sensing as a function of pH. Here, we have used isothermal titration calorimetry to determine the pH dependence of ligand recognition by nine LBDs that cover all major LBD superfamilies, of periplasmic solute-binding proteins, and cytosolic LBDs. We show that periplasmic LBDs recognize ligands over a very broad pH range, frequently stretching over eight pH units. This wide pH range contrasts with a much narrower pH response range of the cytosolic LBDs analyzed. Many LBDs must be dimeric to bind ligands, and analytical ultracentrifugation studies showed that the LBD of the Tar chemoreceptor forms dimers over the entire pH range tested. The pH dependences of Pseudomonas aeruginosa motility and chemotaxis were bell-shaped and centered at pH 7.0. Evidence for pH robustness of signaling in vivo was obtained by Förster Resonance Energy Transfer (FRET) measurements of the chemotaxis pathway responses in Escherichia coli. Bacteria have evolved several strategies to cope with extreme pH, such as periplasmic chaperones for protein refolding. The intrinsic pH resistance of periplasmic LBDs appears to be another strategy that permits bacteria to survive under adverse conditions. IMPORTANCE Demonstration of the pH robustness of extracytoplasmic sensing reveals a previously undescribed evolutionary mechanism that enables bacteria to monitor environmental changes under changing conditions. This mechanism includes the maintenance of the dimeric state of four-helixbundle ligand-binding domains (LBDs). The construction of biosensors is a rapidly growing field of research, and their use to monitor the progression of the COVID-19 pandemic has impressively demonstrated their usefulness. LBDs represent an enormous reservoir of binding modules that can be used to create novel biosensors. Among ligands recognized by LBDs are neurotransmitters, hormones, and quorum-sensing signals. The demonstration that extracytosolic LBDs bind their signals over a wide range of pH values will facilitate the design of biosensors that function under highly variable conditions of acidity and alkalinity.

Chemotaxis of the Human Pathogen Pseudomonas aeruginosa to the Neurotransmitter Acetylcholine.

Acetylcholine is a central biological signal molecule present in all kingdoms of life. In humans, acetylcholine is the primary neurotransmitter of the peripheral nervous system; it mediates signal transmission at neuromuscular junctions. Here, we show that the opportunistic human pathogen Pseudomonas aeruginosa exhibits chemoattraction toward acetylcholine over a concentration range of 1 µM to 100 mM. The maximal magnitude of the response was superior to that of many other P. aeruginosa chemoeffectors. We demonstrate that this chemoattraction is mediated by the PctD (PA4633) chemoreceptor. Using microcalorimetry, we show that the PctD ligand-binding domain (LBD) binds acetylcholine with a equilibrium dissociation constant (KD) of 23 µM. It also binds choline and with lower affinity betaine. Highly sensitive responses to acetylcholine and choline, and less sensitive responses to betaine and l-carnitine, were observed in Escherichia coli expressing a chimeric receptor comprising the PctD-LBD fused to the Tar chemoreceptor signaling domain. We also identified the PacA (ECA_RS10935) chemoreceptor of the phytopathogen Pectobacterium atrosepticum, which binds choline and betaine but fails to recognize acetylcholine. To identify the molecular determinants for acetylcholine recognition, we report high-resolution structures of PctD-LBD (with bound acetylcholine and choline) and PacA-LBD (with bound betaine). We identified an amino acid motif in PctD-LBD that interacts with the acetylcholine tail. This motif is absent in PacA-LBD. Significant acetylcholine chemotaxis was also detected in the plant pathogens Agrobacterium tumefaciens and Dickeya solani. To the best of our knowledge, this is the first report of acetylcholine chemotaxis and extends the range of host signals perceived by bacterial chemoreceptors. IMPORTANCE P. aeruginosa causes a significant number of deaths annually worldwide. For many pathogens, chemotaxis plays an import role in the initial stages of infection, and deciphering the key chomoeffectors and their cognate chemoreceptors may permit the development of strategies to inhibit this process. Genome analyses have shown that many bacteria possess a large number of chemoreceptors. The chemoeffectors recognized by the large majority of chemoreceptors are unknown. However, identifying these chemoeffectors is crucial for deciphering the evolutionary forces that have shaped chemosensory signaling mechanisms in bacteria with different lifestyles. Our current understanding of the relationship between bacterial lifestyle and chemoreceptor repertoire is limited, and this work contributes to closing this gap in our knowledge. By expanding the list of known chemoeffectors and chemoreceptors, progress is made toward identifying functional receptor homologs in other bacteria.

A catalogue of signal molecules that interact with sensor kinases, chemoreceptors and transcriptional regulators.

Bacteria have evolved many different signal transduction systems that sense signals and generate a variety of responses. Generally, most abundant are transcriptional regulators, sensor histidine kinases and chemoreceptors. Typically, these systems recognize their signal molecules with dedicated ligand-binding domains (LBDs), which, in turn, generate a molecular stimulus that modulates the activity of the output module. There are an enormous number of different LBDs that recognize a similarly diverse set of signals. To give a global perspective of the signals that interact with transcriptional regulators, sensor kinases and chemoreceptors, we manually retrieved information on the protein-ligand interaction from about 1,200 publications and 3D structures. The resulting 811 proteins were classified according to the Pfam family into 127 groups. These data permit a delineation of the signal profiles of individual LBD families as well as distinguishing between families that recognize signals in a promiscuous manner and those that possess a well-defined ligand range. A major bottleneck in the field is the fact that the signal input of many signaling systems is unknown. The signal repertoire reported here will help the scientific community design experimental strategies to identify the signaling molecules for uncharacterised sensor proteins.

Direct and Indirect Effects of COVID-19 in Frail Elderly: Interventions and Recommendations.

Frailty is a state of vulnerability to stressors because of a decreased physiological reserve, resulting in poor health outcomes. This state is related to chronic conditions, many of which are risk factors for outcomes in elderly patients having SARS-COV-2. This review aims to describe frailty as a physiological vulnerability agent during the COVID-19 pandemic in elderly patients, summarizing the direct and indirect effects caused by the SARS-COV-2 infection and its prognosis in frail individuals, as well as the interventions and recommendations to reduce their effects. Cohort studies have shown that patients with a Clinical Frailty Scale higher than five have a higher risk of mortality and use of mechanical ventilation after COVID-19; nonetheless, other scales have also associated frailty with longer hospital stays and more severe forms of the disease. Additionally, the indirect effects caused by the pandemic have a negative impact on the health status of older people. Due to the above, a holistic intervention is proposed based on a comprehensive geriatric assessment for frail patients (preventive or post-infection) with emphasis on physical activity and nutritional recommendations, which could be a potential preventive intervention in viral infections by COVID-19.

Rhipicephalus sanguineus Complex in the Americas: Systematic, Genetic Diversity, and Geographic Insights.

The Rhipicephalus sanguineus group encompasses at least 12 validated species of Palearctic and Afrotropical hard ticks, which are relevant in veterinary medicine and public health. The taxonomy of R. sanguineus s.s., has been particularly intensely debated, due to its wide geographic distribution, morphological variants, parasite-host associations, and its capacity and vectorial competence for the transmission of several pathogens. By sequencing mitochondrial markers, it was possible to identify the existence of multiple lineages, among which the Tropical and the Temperate lineages stand out, particularly in America. However, the northern limit between these lineages is not clear due to the lack of extensive sampling across Mexico. For this reason, the aim of the present study was to determine the genetic diversity and structure of the R. sanguineus group in Mexico and to compare it with the populations reported in the Americas, in order to propose the northern limit of the R. sanguineus Tropical lineage and the potential regions of sympatry with R. sanguineus s.s. The findings of this study now confirm the presence of R. sanguineus s.s. in Mexico, showing a subtle genetic structure and high genetic diversity throughout its distribution in the Americas. In contrast, the Tropical lineage seems to be genetically less diverse in its overall distribution in the Americas. The genetic diversity of these two independent lineages could have important epidemiological implications in the transmission of tick pathogens.

Gastrectomía por cáncer gástrico: abordaje mínimamente invasivo / Gastrectomy for gastric cancer: Minimally invasive approach

Introducción. El cáncer gástrico en nuestro país es una de las neoplasias más comunes y su diagnóstico generalmente se realiza en estadios avanzados. El objetivo de este estudio fue describir las características sociodemográficas y clínicas, la experiencia quirúrgica, y las complicaciones en los pacientes con cáncer gástrico.Métodos. Se presenta una serie de casos en la que se revisaron las historias clínicas de pacientes con diagnóstico histológico de adenocarcinoma gástrico, a quienes se les practicó gastrectomía mínimamente invasiva en el Instituto Nacional de Cancerología de Bogotá D.C., Colombia, entre enero de 2012 y diciembre de 2018.Resultados. Se realizó gastrectomía por laparoscopia convencional en 31 pacientes (75,6 %) y por laparoscopia asistida por robot en 10 pacientes (24,4 %). Los estadios clínicos fueron IA en 20 pacientes (48,7 %), IB en tres (7,3 %), IIA en nueve (21,9%), IIB en cinco (12,2 %) y IIIA en cuatro pacientes (9,7 %). Se realizaron 24 gastrectomías totales (58,5 %) y 17 distales (41,4 %). No hubo muertes intraoperatorias ni posoperatorias a 30 días. La disección ganglionar predominante fue D2 en el 92,6 % (n=38) de los casos. Se presentaron complicaciones posoperatorias en el 17,1 % (n=7).Discusión. La gastrectomía por cáncer gástrico realizada por vía laparoscópica convencional y la asistida por robot, parecen ser procedimientos seguros y factibles. La determinación de supervivencia libre de enfermedad y mortalidad asociada a cáncer será necesaria para establecer la seguridad oncológica de este tipo de procedimientos en nuestro medio

Introduction. In our country, gastric cancer is one of the most common neoplasms and its diagnosis is generally made in advanced stages. The objective of this study was to describe the sociodemographic and clinical characteristics, surgical experience, and complications in patients with gastric cancer. In our country, gastric cancer is one of the most common neoplasms and its diagnosis is generally made in advanced stages. The objective of this study was to describe the sociodemographic and clinical characteristics, surgical experience, and complications in patients with gastric cancer.Methods. A series of cases is presented in which the medical records of patients with a histological diagnosis of gastric adenocarcinoma, who underwent minimally invasive gastrectomy at the National Cancer Institute of Bogotá, Colombia, between January 2012 and December 2018. Results. Conventional laparoscopic gastrectomy was performed in 31 patients (75.6%) and by robot-assisted laparoscopy in 10 patients (24.4%). The clinical stages were IA in 20 patients (48.7%), IB in three (7.3%), IIA in nine (21.9%), IIB in five (12.2%), and IIIA in four patients (9.7%). Twenty-four total gastrectomies (58.5%) and 17 distal gastrectomies (41.4%) were performed. There were no intraoperative or postoperative deaths at 30 days. The predominant lymph node dissection was D2 in 92.6% (n = 38) of the cases. Postoperative complications occurred in 17.1% (n=7). Discussion. Gastrectomy due to gastric cancer, performed by conventional laparoscopic and robot-assisted approaches, appear to be safe and feasible procedures. The determination of disease-free survival and cancer-associated mortality will be necessary to establish the oncological safety of this type of procedure in our environment

Patients With Unexplained Dilated Pancreatic Duct Have High Risk of Biliopancreatic Malignancy Detected by EUS.

INTRODUCTION: Patients with unexplained dilated common bile duct (CBD) and/or dilated main pancreatic duct (MPD) on noninvasive abdominal imaging tests are often referred for endoscopic ultrasound (EUS) in order to rule out biliopancreatic cancer. The aim of the study was to evaluate the diagnostic yield of EUS in this patient group. METHODS: A prospective study was conducted. Patients with unexplained dilated CBD and/or MPD on abdominal imaging, who underwent EUS, were enrolled. RESULTS: Fifty-four patients underwent EUS (CBD dilation n=38, MPD dilation n=5 or both n=11). In 31/54 patients (57.4%), EUS revealed pathologic findings. Sixteen patients (29.6%) had EUS evidence of biliopancreatic cancer and 15 patients (27.7%) had benign pathology. Ten (62.5%) of the patients with biliopancreatic cancer had MPD dilation. MPD dilation was significantly associated with malignancy (P=0.017). CONCLUSION: Patients with unexplained dilated MPD on noninvasive image have a high risk of biliopancreatic malignancy detected by EUS.

Pseudomonas aeruginosa as a Model To Study Chemosensory Pathway Signaling.

Bacteria have evolved a variety of signal transduction mechanisms that generate different outputs in response to external stimuli. Chemosensory pathways are widespread in bacteria and are among the most complex signaling mechanisms, requiring the participation of at least six proteins. These pathways mediate flagellar chemotaxis, in addition to controlling alternative functions such as second messenger levels or twitching motility. The human pathogen Pseudomonas aeruginosa has four different chemosensory pathways that carry out different functions and are stimulated by signal binding to 26 chemoreceptors. Recent research employing a diverse range of experimental approaches has advanced enormously our knowledge on these four pathways, establishing P. aeruginosa as a primary model organism in this field. In the first part of this article, we review data on the function and physiological relevance of chemosensory pathways as well as their involvement in virulence, whereas the different transcriptional and posttranscriptional regulatory mechanisms that govern pathway function are summarized in the second part. The information presented will be of help to advance the understanding of pathway function in other organisms.

The genus Rickettsia in Mexico: Current knowledge and perspectives.

The genus Rickettsia encompasses 35 valid species of intracellular, coccobacilli bacteria that can infect several eukaryotic taxa, causing multiple emerging and re-emerging diseases worldwide. This work aimed to gather and summarise the current knowledge about the genus Rickettsia in Mexico, updating the taxonomy of the bacteria and their hosts by including all the records available until 2020, to elucidate host-parasite relationships and determine the geographical distribution of each Rickettsia species present in the country. Until now, 14 species of Rickettsia belonging to four groups have been recorded in Mexico. These species have been associated with 26 arthropod species (14 hard ticks, three soft ticks, two sucking lice, and seven fleas) and 17 mammal species distributed over 30 states in Mexico. This work highlights the high biological inventory of rickettsias for Mexico and reinforces the need to approach the study of this group from a One Health perspective.

Reduction of alternative electron acceptors drives biofilm formation in Shewanella algae.

Shewanella spp. possess a broad respiratory versatility, which contributes to the occupation of hypoxic and anoxic environmental or host-associated niches. Here, we observe a strain-specific induction of biofilm formation in response to supplementation with the anaerobic electron acceptors dimethyl sulfoxide (DMSO) and nitrate in a panel of Shewanella algae isolates. The respiration-driven biofilm response is not observed in DMSO and nitrate reductase deletion mutants of the type strain S. algae CECT 5071, and can be restored upon complementation with the corresponding reductase operon(s) but not by an operon containing a catalytically inactive nitrate reductase. The distinct transcriptional changes, proportional to the effect of these compounds on biofilm formation, include cyclic di-GMP (c-di-GMP) turnover genes. In support, ectopic expression of the c-di-GMP phosphodiesterase YhjH of Salmonella Typhimurium but not its catalytically inactive variant decreased biofilm formation. The respiration-dependent biofilm response of S. algae may permit differential colonization of environmental or host niches.

Bacterial Succession through the Artisanal Process and Seasonal Effects Defining Bacterial Communities of Raw-Milk Adobera Cheese Revealed by High Throughput DNA Sequencing.

The bacterial community of the artisanal Adobera cheese from Los Altos de Jalisco was described through high-throughput sequencing of 16S rRNA gene libraries. Samples were collected in two different seasons (dry and rainy) during four key steps of the manufacturing process (raw milk, fresh curd, matured curd, and cheese). Bacterial diversity was higher in early steps in comparison with the final elaboration stages. Firmicutes and Proteobacteria were the most abundant phyla, strongly represented by the Streptococcaceae, Enterobacteriaceae and Lactobacillaceae families, and core bacteria genera such as Streptococcus spp., Lactococcus spp., and Lactobacillus spp. Undesirable bacteria, including Pseudomonas spp. and Acinetobacter spp., were also detected in raw milk but almost undetectable at the end of the cheese manufacturing process, and seemed to be displaced by lactic-acid bacteria-related genera. Seasonal effects were observed on the community structure but did not define the core microbiota composition. Predictive metabolism was related to membrane transport, and amino-acid, lipid, and carbohydrate metabolism pathways. Our results contribute to deduce the role of bacteria involved in Adobera cheese manufacturing in terms of the metabolism involved, cheese microbial safety, and how undesirable bacterial populations could be regulated by process standardization as a potential tool to improve safety.

Reproductive incompatibility between Amblyomma maculatum (Acari: Ixodidae) group ticks from two disjunct geographical regions within the USA.

The Amblyomma maculatum Koch group of ixodid ticks consists of three species: A. maculatum, A. triste, and A. tigrinum. However, since Koch described this group in 1844, the systematics of its members has been the subject of ongoing debate. This is especially true of A. maculatum and A. triste; recent molecular analyses reveal insufficient genetic divergence to separate these as distinct species. Further confounding this issue is the discovery in 2014 of A. maculatum group ticks in southern Arizona (AZ), USA, that share morphological characteristics with both A. triste and A. maculatum. To biologically evaluate the identity of A. maculatum group ticks from southern Arizona, we analyzed the reproductive compatibility between specimens of A. maculatum group ticks collected from Georgia (GA), USA, and southern Arizona. Female ticks from both Arizona and Georgia were mated with males from both the Georgia and Arizona Amblyomma populations, creating two homologous and two heterologous F1 cohorts of ticks: GA ♀/GA ♂, AZ ♀/AZ ♂, GA ♀/AZ ♂, and AZ ♀/GA ♂. Each cohort was maintained separately into the F2 generation with F1 females mating only with F1 males from their same cohort. Survival and fecundity parameters were measured for all developmental stages. The observed survival parameters for heterologous cohorts were comparable to those of the homologous cohorts through the F1 generation. However, the F1 heterologous females produced F2 egg clutches that did not hatch, thus indicating that the Arizona and Georgia populations of A. maculatum group ticks tested here represent different biological species.

Distribution and Occurrence of Amblyomma maculatum sensu lato (Acari: Ixodidae) and Rickettsia parkeri (Rickettsiales: Rickettsiaceae), Arizona and New Mexico, 2017-2019.

Amblyomma maculatum Koch sensu lato (s.l.) ticks are the vector of Rickettsia parkeri in Arizona, where nine cases of R. parkeri rickettsiosis have been identified since the initial case in 2014. The current study sought to better define the geographic ranges of the vector and pathogen and to assess the potential public health risk posed by R. parkeri in this region of the southwestern United States. A total of 275 A. maculatum s.l. ticks were collected from 34 locations in four counties in Arizona and one county in New Mexico and screened for DNA of Rickettsia species. Rickettsia parkeri was detected in 20.4% of the ticks, including one specimen collected from New Mexico, the first report of R. parkeri in A. maculatum s.l. from this state. This work demonstrates a broader distribution of A. maculatum s.l. ticks and R. parkeri in the southwestern United States than appreciated previously to suggest that R. parkeri rickettsiosis is underrecognized in this region.