RESUMEN

Sepsis is a complex condition of inflammatory and immune dysregulation, triggered by severe infection. In survivors, chronic inflammation and immune dysregulation linger, facilitating the emergence of infections. CD8 dysfunction contributes to immunosuppression in sepsis survivors. We devised an animal model that enabled us to identify and analyze CD8-intrinsic defects induced by sepsis. We adoptively transferred CD45.1 CD8 OT-I T cells into CD45.2 congenic mice and subjected them to cecal ligature and puncture, to induce abdominal sepsis. One month later, we isolated the transferred CD8 cells. Surface marker expression confirmed they had not been activated through the TCR. CD8 OT-I T cells isolated from septic (or sham-operated) mice were transferred to second recipients, which were challenged with OVA-expressing Listeria monocytogenes. We compared effector capacities between OT-I cells exposed to sepsis and control cells. Naive mice that received OT-I cells exposed to sepsis had higher bacterial burden and a shorter survival when challenged with OVA-expressing L. monocytogenes. OT-I cells isolated from septic mice produced less IFN-γ but had conserved activation, expansion potential, and cytotoxic function. We observed lower transcript levels of IFN-γ and of the long noncoding RNA Ifng-as1, a local regulator of the epigenetic landscape, in cells exposed to sepsis. Accordingly, local abundance of a histone modification characteristic of active promoter regions was reduced in sepsis-exposed CD8 T cells. Our results identify a mechanism through which inflammation in the context of sepsis affects CD8 T cell function intrinsically.

Asunto(s)

RESUMEN

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxykynurenine (3-HK) protects from lethal bacterial infection. 3-HK, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages through a systemic mechanism that targets kainate-sensitive glutamate receptors. These findings reveal a new pathway by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with important implications for the coordination between the immune and nervous systems in pathological conditions.

RESUMEN

Muscle strength declines ∼3% per year after the age of 70. Resistance training guidelines for older adults are often based on free-weight and machine exercises, which may be inaccessible and lack carryover to activities of daily living. We tested the hypothesis that resistance training adaptations in older adults are task-specific. Thirty adults (8 males, 22 females; mean age = 71 years) were randomly assigned to participate in 6 weeks of supervised, high-intensity resistance training (twice per week) utilizing free-weight and machine exercises (traditional) versus functional activities that were overloaded with a weighted vest (functional). Participants were thoroughly familiarized with the exercises and testing prior to beginning the study. Major outcome measures included assessments of functional performance, five-repetition maximum strength, isometric knee extensor force, and quadriceps muscle size. Physical activity and nutrition were monitored. The study results demonstrate that the magnitude of improvement within a given outcome was largely dependent on group assignment, with greater improvements in gait speed and the timed-up-and-go in the functional group, but 2-3× greater five repetition maximum strength improvements for the trap bar deadlift, leg press, and leg extension following traditional resistance training. Both groups showed improvements in isometric knee extensor force and muscle size, suggesting that some aspects of the observed adaptations were generic, rather than specific. Overall, these novel findings suggest that, among older adults, 1) resistance training adaptations exhibit a high degree of task specificity and 2) significant improvements in functional outcomes can be achieved with the use of a weighted vest.

RESUMEN

Adult survivors of childhood sexual abuse (CSA) may experience emotional, social, and psychological difficulties, heightened due to the interpersonal nature of harm. Despite the demonstrated effectiveness of trauma-focused treatments in the West, a culturally specific understanding of the needs of and treatments for survivors in South Asia is still in its infancy. The study aimed to systematically review research findings on the mental health impacts of CSA on adult survivors and current treatment approaches and their efficacy and acceptability in South Asia. Seven databases (Scopus, Ovid, CINAHL, ProQuest, EThOS, Google Scholar, and Dogpile) and five peer-reviewed South Asian journals were searched from inception until March 30, 2023. Searches included participants who were adult survivors of CSA of South Asian origin residing in South Asia. Studies on their mental health, different treatments, and the efficacy and acceptability of these treatments were included. Quality assessment tools were used to appraise the quality of included studies. The results were synthesized narratively. A total of 3,362 records were retrieved, and 24 articles were included in the final review. Twenty studies reported mental health impacts of CSA on adult survivors, four studies reported current treatments offered, and two studies were on recovery. However, no study focused on the efficacy or acceptability of the treatments being delivered. Even though the needs of adult CSA survivors in South Asia have been partly identified, there is very little research into the treatments for them.

Asunto(s)

RESUMEN

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxy-kynurenine protects from lethal gram-negative bacterial infection. 3-hydroxy-kynurenine, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages by targeting kainate-sensitive glutamate receptors. These findings reveal new mechanisms by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with significant implications for the coordination between the immune and nervous systems in pathological conditions.

RESUMEN

Portal hypertension may have major consequences on the pulmonary vasculature due to the complex pathophysiological interactions between the liver and lungs. Portopulmonary hypertension (PoPH), a subset of group 1 pulmonary hypertension (PH), is a serious pulmonary vascular disease secondary to portal hypertension, and is the fourth most common subtype of pulmonary arterial hypertension. It is most commonly observed in cirrhotic patients; however, patients with noncirrhotic portal hypertension can also develop it. On suspicion of PoPH, the initial evaluation is by a transthoracic echocardiogram in which, if elevated pulmonary pressures are shown, patients should undergo right heart catheterization to confirm the diagnosis. The prognosis is extremely poor in untreated patients; therefore, management includes pulmonary arterial hypertension therapies with the aim of improving pulmonary hemodynamics and moving patients to orthotopic liver transplantation (OLT). In this article, we review in detail the epidemiology, pathophysiology, process for diagnosis, and most current treatments including OLT and prognosis in patients with PoPH. In addition, we present a diagnostic algorithm that includes the current criteria to properly select patients with PoPH who are candidates for OLT.

RESUMEN

Facultative marine bacterial pathogens sense environmental signals so that the expression of virulence factors is upregulated on entry into hosts and downregulated during the free-living lifestyle in the environment. In this study, we utilized transcriptome sequencing to compare the transcriptional profiles of Photobacterium damselae subsp. damselae, a generalist pathogen that causes disease in diverse marine animals and fatal infections in humans at NaCl concentrations that mimic the free-living lifestyle or host internal milieu, respectively. We here show that NaCl concentration constitutes a major regulatory signal that shapes the transcriptome and uncover 1,808 differentially expressed genes (888 upregulated and 920 downregulated in response to low-salt conditions). Growth at 3% NaCl, a salinity that mimics the free-living lifestyle, upregulated genes involved in energy production, nitrogen metabolism, transport of compatible solutes, utilization of trehalose and fructose, and carbohydrate and amino acid metabolism with strong upregulation of the arginine deiminase system (ADS). In addition, we observed a marked increase in resistance to antibiotics at 3% NaCl. On the contrary, the low salinity conditions (1% NaCl) that mimic those encountered in the host triggered a virulence gene expression profile that maximized the production of the type 2 secretion system (T2SS)-dependent cytotoxins damselysin, phobalysin P, and a putative PirAB-like toxin, observations that were corroborated by the analysis of the secretome. Low salinity also upregulated the expression of iron-acquisition systems, efflux pumps, and other functions related to stress response and virulence. The results of this study greatly expand our knowledge of the salinity-responsive adaptations of a generalist and versatile marine pathogen. IMPORTANCE Pathogenic Vibrionaceae species experience continuous shifts of NaCl concentration in their life cycles. However, the impact of salinity changes in gene regulation has been studied in a small number of Vibrio species. In this study, we analyzed the transcriptional response of Photobacterium damselae subsp. damselae (Pdd), a generalist and facultative pathogen, to changes in salinity, and demonstrate that growth at 1% NaCl in comparison to 3% NaCl triggers a virulence program of gene expression, with a major impact in the T2SS-dependent secretome. The decrease in NaCl concentration encountered by bacteria on entry into a host is proposed to constitute a regulatory signal that upregulates a genetic program involved in host invasion and tissue damage, nutrient scavenging (notably iron), and stress responses. This study will surely inspire new research on Pdd pathobiology, as well as on other important pathogens of the family Vibrionaceae and related taxa whose salinity regulons still await investigation.

Asunto(s)

RESUMEN

Dr. Vicente Izquierdo San Fuentes was the first professor of Histology at the Faculty of Medicine of the University of Chile. In that Chair, cell theory strongly radiated to new generations of health students. However, the conditions for the creation of the discipline of General or Cell Biology were not yet ripe. Almost three decades later, Dr. Juan Noé Crevani was hired in Italy to lead Medical Zoology in 1912. From the heterogeneous discipline of Medical Zoology, Dr. Noé managed to create in 1926 the new chairs of General Biology, Embryology-Comparative Anatomy and Parasitology. His vision of biology as an essentially dynamic and experimental science, contributed to modernize and encourage the development of different areas of biology in Chile. Retaining their full independence, these chairs met in 1931, in a new organization called the Juan Noé Institute of Biology, which lasted until the university reform of 1968. Afterwards, the departments of Biology and Genetics, Parasitology, Human Anatomy and Histology were created. In 1998, a new reorganization of the Faculty of Medicine of the University of Chile began, creating the so-called Institute of Biomedical Sciences (ICBM) that houses several disciplinary programs that replaced the old departments.

Asunto(s)

RESUMEN

The marine bacterium Photobacterium damselae subsp. piscicida (Pdp) causes photobacteriosis in fish and important financial losses in aquaculture, but knowledge of its virulence factors is still scarce. We here demonstrate that an unstable plasmid (pPHDPT3) that encodes a type III secretion system (T3SS) is highly prevalent in Pdp strains from different geographical origins and fish host species. We found that pPHDPT3 undergoes curing upon in vitro cultivation, and this instability constitutes a generalized feature of pPHDPT3-like plasmids in Pdp strains. pPHDPT3 markers were detected in tissues of naturally-infected moribund fish and in the Pdp colonies grown directly from the fish tissues but were undetectable in a fraction of the colonies produced upon the first passage of the primeval colonies on agar plates. Notably, cured strains exhibited a marked reduction in virulence for fish, demonstrating that pPHDPT3 is a major virulence factor of Pdp. The attempts to stabilize pPHDPT3 by insertion of antibiotic resistance markers by allelic exchange caused an even greater reduction in virulence. We hypothesize that the existence of a high pressure to shed pPHDPT3 plasmid in vitro caused the selection of clones with off-target mutations and gene rearrangements during the process of genetic modification. Collectively, these results show that pPHDPT3 constitutes a novel, hitherto unreported virulence factor of Pdp that shows a high instability in vitro and warn that the picture of Pdp virulence genes has been historically underestimated, since the loss of the T3SS and other plasmid-borne genes may have occurred systematically in laboratories for decades.

Asunto(s)

RESUMEN

Dr. Vicente Izquierdo San Fuentes was the first professor of Histology at the Faculty of Medicine of the University of Chile. In that Chair, cell theory strongly radiated to new generations of health students. However, the conditions for the creation of the discipline of General or Cell Biology were not yet ripe. Almost three decades later, Dr. Juan Noé Crevani was hired in Italy to lead Medical Zoology in 1912. From the heterogeneous discipline of Medical Zoology, Dr. Noé managed to create in 1926 the new chairs of General Biology, Embryology-Comparative Anatomy and Parasitology. His vision of biology as an essentially dynamic and experimental science, contributed to modernize and encourage the development of different areas of biology in Chile. Retaining their full independence, these chairs met in 1931, in a new organization called the Juan Noé Institute of Biology, which lasted until the university reform of 1968. Afterwards, the departments of Biology and Genetics, Parasitology, Human Anatomy and Histology were created. In 1998, a new reorganization of the Faculty of Medicine of the University of Chile began, creating the so-called Institute of Biomedical Sciences (ICBM) that houses several disciplinary programs that replaced the old departments.

Asunto(s)

RESUMEN

The marine bacterium Photobacterium damselae subsp. damselae (Pdd) causes disease in marine animals and humans. Previous studies demonstrated that mutation of the two-component system RstAB strongly impacts virulence of this pathogen, but the RstAB regulon has not been thoroughly elucidated. We here compared the transcriptomes of Pdd RM-71 and ΔrstA and ΔrstB derivatives using RNA-seq. In accordance with previous studies, RstAB positively regulated cytotoxins Dly, PhlyP and PhlyC. This analysis also demonstrated a positive regulation of outer membrane proteins, resistance against antimicrobials and potential virulence factors by this system. Remarkably, RstAB positively regulated two hitherto uncharacterised gene clusters involved in the synthesis of a polysaccharide capsule. Presence of a capsular layer in wild-type cells was confirmed by transmission electron microscopy, whereas rstA and rstB mutants were non-capsulated. Mutants for capsule synthesis genes, wza and wzc exhibited acapsular phenotypes, were impaired in resistance against the bactericidal action of fish serum and mucus, and were strongly impaired in virulence for fish, indicating a major role of capsule in virulence. Collectively, this study demonstrates that RstAB is a major positive regulator of key virulence factors including a polysaccharide capsule essential for full virulence in a pathogenic Photobacterium.

Asunto(s)

RESUMEN

La coexistencia entre cáncer de tiroides e hipertiroidismo es infrecuente, y la mayoría de las lesiones nodulares a partir de las cuales se documenta un tumor maligno en este grupo de pacientes corresponden a nódulos fríos. Justificado en el creciente número de reportes en la literatura acerca de tumores malignos diagnosticados a partir de nódulos calientes, se realizó una revisión sistemática que tuvo como objetivo determinar los posibles factores asociados con el diagnóstico de cáncer de tiroides a partir de nódulos calientes en pacientes con hipertiroidismo. Los resultados sugieren que el diagnóstico clínico de bocio nodular tóxico, lesiones nodulares de diámetro mayor de 10 mm y tipo histológico compatible con carcinoma folicular, son factores que aumentan por sí solos el riesgo de realizar el diagnóstico de cáncer a partir de un nódulo caliente

Coexistence between thyroid cancer and hyperthyroidism is rare, and most of the nodular lesions from which a malignant tumor is documented in this group of patients correspond to cold nodules. Justified by the increasing number of reports in the literature about malignant tumors diagnosed from hot nodules, a systematic review was carried out to determine possible factors associated with the diagnosis of thyroid cancer from hot nodules in pa-tients with hyperthyroidism. The results suggest that the clinical diagnosis of toxic nodular goiter, nodular lesions of diameter > 10 mm and a histological type compatible with a follicular carcinoma, are factors that on their own increase the risk of making the diagnosis of cancer from a hot nodule

Asunto(s)

RESUMEN

Abstract Coexistence between thyroid cancer and hyperthyroidism is rare, and most of the nodular lesions from which a malignant tumor is documented in this group of patients correspond to cold nodules. Justified by the increasing number of reports in the literature about malignant tumors diagnosed from hot nodules, a systematic review was carried out to determine possible factors associated with the diagnosis of thyroid cancer from hot nodules in patients with hyperthyroidism. The results suggest that the clinical diagnosis of toxic nodular goiter, nodular lesions of diameter > 10 mm and a histological type compatible with a follicular carcinoma, are factors that on their own increase the risk of making the diagnosis of cancer from a hot nodule.

Resumen La coexistencia entre cáncer de tiroides e hipertiroidismo es infrecuente, y la mayoría de las lesiones nodulares a partir de las cuales se documenta un tumor maligno en este grupo de pacientes corresponden a nódulos fríos. Justificado en el creciente número de reportes en la literatura acerca de tumores malignos diagnosticados a partir de nódulos calientes, se realizó una revisión sistemática que tuvo como objetivo determinar los posibles factores asociados con el diagnóstico de cáncer de tiroides a partir de nódulos calientes en pacientes con hipertiroidismo. Los resultados sugieren que el diagnóstico clínico de bocio nodular tóxico, lesiones nodulares de diámetro mayor de 10 mm y tipo histológico compatible con carcinoma folicular, son factores que aumentan por sí solos el riesgo de realizar el diagnóstico de cáncer a partir de un nódulo caliente.

Asunto(s)

RESUMEN

The aim of the present study was to elucidate how fructose is able to increase the rate of ethanol metabolism in the liver, an observation previously termed the fructose effect. Previous studies suggest that an increase in ATP consumption driven by glucose synthesis from fructose stimulates the oxidation of NADH in the mitochondrial respiratory chain, allowing faster oxidation of ethanol by alcohol dehydrogenase; however, this idea has been frequently challenged. We tested the effects of fructose, sorbose and tagatose both in vitro and in vivo. Both ethanol and each sugar were either added to isolated hepatocytes or injected intraperitoneally in the rat. In the in vitro experiments, samples were taken from the hepatocyte suspension in a time-dependent manner and deproteinized with perchloric acid. In the in vivo experiments, blood samples were taken every 15 min and the metabolites were determined in the plasma. These metabolites include ethanol, glucose, glycerol, sorbitol, lactate, fructose and sorbose. Ethanol oxidation by rat hepatocytes was increased by more than 50% with the addition of fructose. The stimulation was accompanied by increased glucose, glycerol, lactate and sorbitol production. A similar effect was observed with sorbose, while tagatose had no effect. The same pattern was observed in the in vivo experiments. This effect was abolished by inhibiting alcohol dehydrogenase with 4-methylpyrazole, whereas inhibition of the respiratory chain with cyanide did not affect the fructose effect. In conclusion, present results provide evidence that, by reducing glyceraldehyde and glycerol and fructose to sorbitol, respectively, NADH is consumed, allowing an increase in the elimination of ethanol. Hence, this effect is not linked to a stimulation of mitochondrial re-oxidation of NADH driven by ATP consumption.

Asunto(s)

RESUMEN

Peptidoglycan (PG) is a major component of the bacterial cell wall, forming a mesh-like structure enwrapping the bacteria that is essential for maintaining structural integrity and providing support for anchoring other components of the cell envelope. PG biogenesis is highly dynamic and requires multiple enzymes, including several hydrolases that cleave glycosidic or amide bonds in the PG. This work describes the structural and functional characterization of an NlpC/P60-containing peptidase from Photobacterium damselae subsp. piscicida (Phdp), a Gram-negative bacterium that causes high mortality of warm-water marine fish with great impact for the aquaculture industry. PnpA ( PhotobacteriumNlpC-like protein A) has a four-domain structure with a hydrophobic and narrow access to the catalytic center and specificity for the γ-d-glutamyl-meso-diaminopimelic acid bond. However, PnpA does not cleave the PG of Phdp or PG of several Gram-negative and Gram-positive bacterial species. Interestingly, it is secreted by the Phdp type II secretion system and degrades the PG of Vibrio anguillarum and Vibrio vulnificus This suggests that PnpA is used by Phdp to gain an advantage over bacteria that compete for the same resources or to obtain nutrients in nutrient-scarce environments. Comparison of the muropeptide composition of PG susceptible and resistant to the catalytic activity of PnpA showed that the global content of muropeptides is similar, suggesting that susceptibility to PnpA is determined by the three-dimensional organization of the muropeptides in the PG.IMPORTANCE Peptidoglycan (PG) is a major component of the bacterial cell wall formed by long chains of two alternating sugars interconnected by short peptides, generating a mesh-like structure that enwraps the bacterial cell. Although PG provides structural integrity and support for anchoring other components of the cell envelope, it is constantly being remodeled through the action of specific enzymes that cleave or join its components. Here, it is shown that Photobacterium damselae subsp. piscicida, a bacterium that causes high mortality in warm-water marine fish, produces PnpA, an enzyme that is secreted into the environment and is able to cleave the PG of potentially competing bacteria, either to gain a competitive advantage and/or to obtain nutrients. The specificity of PnpA for the PG of some bacteria and its inability to cleave others may be explained by differences in the structure of the PG mesh and not by different muropeptide composition.

Asunto(s)

RESUMEN

Membrane tension plays an inhibitory role in clathrin-mediated endocytosis (CME) by impeding the transition of flat plasma membrane to hemispherical clathrin-coated structures (CCSs). Membrane tension also impedes the transition of hemispherical domes to omega-shaped CCSs. However, CME is not completely halted in cells under high tension conditions. Here we find that epsin, a membrane bending protein which inserts its N-terminus H0 helix into lipid bilayer, supports flat-to-dome transition of a CCS and stabilizes its curvature at high tension. This discovery is supported by molecular dynamic simulation of the epsin N-terminal homology (ENTH) domain that becomes more structured when embedded in a lipid bilayer. In addition, epsin has an intrinsically disordered protein (IDP) C-terminus domain which induces membrane curvature via steric repulsion. Insertion of H0 helix into lipid bilayer is not sufficient for stable epsin recruitment. Epsin's binding to adaptor protein 2 and clathrin is critical for epsin's association with CCSs under high tension conditions, supporting the importance of multivalent interactions in CCSs. Together, our results support a model where the ENTH and unstructured IDP region of epsin have complementary roles to ensure CME initiation and CCS maturation are unimpeded under high tension environments.

Asunto(s)

RESUMEN

The ability to metabolize sucrose is a variable trait within the family Vibrionaceae. The marine bacterium Photobacterium damselae subsp. damselae (Pdd), pathogenic for marine animals and humans, is generally described as negative for sucrose utilization (Scr-). Previous studies have reported sucrose-utilizing isolates (Scr+), but the genetic basis of this variable phenotype remains uncharacterized. Here, we carried out the genome sequencing of five Scr+ and two Scr- Pdd isolates and conducted a comparative genomics analysis with sixteen additional Pdd genomes sequenced in previous studies. We identified two different versions of a four-gene cluster (scr cluster) exclusive of Scr+ isolates encoding a PTS system sucrose-specific IIBC component (scrA), a fructokinase (scrK), a sucrose-6-phosphate hydrolase (scrB), and a sucrose operon repressor (scrR). A scrA deletion mutant did not ferment sucrose and was impaired for growth with sucrose as carbon source. Comparative genomics analyses suggested that scr clusters were acquired by horizontal transfer by different lineages of Pdd and were inserted into a recombination hot-spot in the Pdd genome. The incongruence of phylogenies based on housekeeping genes and on scr genes revealed that phylogenetically diverse gene clusters for sucrose utilization have undergone extensive horizontal transfer among species of Vibrio and Photobacterium.

Asunto(s)

RESUMEN

INTRODUCTION: The hypothesis of an association between papillary thyroid carcinoma (PTC) and chronic lymphocytic thyroiditis (CLT) continues to generate debate. Retrospective studies suggest that there is a greater probability of diagnosing a PTC in surgical specimens with CLT; however, prospective studies suggest that there is no true increase in risk. METHODS: An analytical, cross-section measurement and retrospective study was carried out considering gender, age and diagnosis of CLT and PTC in surgical specimens. A binary logistic regression model was proposed to predict the probability of carrying out the diagnosis of PTC based on the diagnosis of CLT, gender and age. RESULTS: The study population consisted of 1136 patients, 1047 (92.2%) women and 89 (7.8%) men, with an average age of 47.5±14.3 years. The prevalence of CLT and PTC was 14.9% and 16.1% respectively. Coexistence between PTC and CLT was found in 44 patients, corresponding to 3.9% of the population. Our logistic regression model suggests that the probability of diagnosing PTC in surgical specimens of male patients under 40 years old and with CLT is 53.8%. CONCLUSIONS: We suggest that there is a greater probability of diagnosing PTC in surgical specimens with confirmatory histological data for CLT; in addition, in males under 40 years old this probability increases

INTRODUCCIÓN: La hipótesis que sugiere una asociación entre el cáncer papilar de tiroides (PTC, por sus siglas en inglés) y la tiroiditis linfocítica crónica (CLT, por sus siglas en inglés) sigue generando debate. Los estudios retrospectivos sugieren que existe una mayor probabilidad de realizar un diagnóstico de PTC en las muestras quirúrgicas de CLT. Los estudios prospectivos sugieren que no existe un incremento real del riesgo. MÉTODOS: Se realizó un estudio analítico de medición transversal y temporalidad retrospectiva en cuanto a sexo, edad, diagnóstico de CLT y espécimen quirúrgico de PTC. Se propuso un modelo de regresión logística binaria para predecir la probabilidad de realizarse un diagnóstico de PTC basado en el diagnóstico de CLT, sexo y edad. RESULTADOS: La población de estudio consistió en 1.136 pacientes, 1.047 mujeres (92,2%) y 89 varones (7,8%), con una edad media de 47,5 ± 14,3 años. La prevalencia de CLT y PTC fue del 14,9% y 16,1%, respectivamente. La coexistencia de PTC y CLT fue encontrada en 44 pacientes, correspondiente al 3,9% de la población. Nuestro modelo de regresión logística sugiere que la probabilidad de realizar el diagnóstico de PTC en muestras quirúrgicas de pacientes varones con edades inferiores a 40 años y con CLT es del 53,8%. CONCLUSIONES: Sugerimos que existe una mayor probabilidad de diagnosticar PTC en muestras quirúrgicas con datos histológicos confirmatorios de CLT; además, esta probabilidad puede modificarse sobre la base de sexo masculino y edad superior a 40 años

Asunto(s)

RESUMEN

Photobacterium damselae subsp. damselae (Pdd), an important pathogen for marine animals, is also an opportunistic human pathogen that can cause fatal necrotizing fasciitis. The regulatory changes triggered by the temperature shift experienced by this marine pathogen upon entering the human body, are completely unknown. Here we report an RNA-seq approach combined with phenotypical assays to study the response of Pdd to cultivation at 37°C in comparison to 25°C. We found that cultivation of a Pdd highly virulent strain for fish and mice, RM-71, at 37°C, initially enhanced bacterial growth in comparison to 25°C as evidenced by the increase in optical density. However, cells were found to undergo a progressive loss of viability after 6 h cultivation at 37°C, and no viable cells could be detected from 30 h cultures at 37°C. In contrast, at 25°C, viable cell counts achieved the highest values at 30 h cultivation. Cells grown at 25°C showed normal rod morphology by scanning electron microscopy analysis whereas cells grown at 37°C exhibited chain-like structures and aberrant long shapes suggesting a defect in daughter cell separation and in septum formation. Cells grown at 37°C also exhibited reduced tolerance to benzylpenicillin. Using a RNA-seq approach we discovered that growth at 37°C triggered a heat-shock response, whereas genes involved in motility and virulence were repressed including iron acquisition systems, the type two secretion system, and damselysin toxin, a major virulence factor of Pdd. Human isolates did not exhibit advantage growing at 37°C compared to fish isolates, and comparative genomics did not reveal gene markers specific of human isolates, suggesting that any Pdd genotype existing in the marine environment might potentially cause disease in humans. Altogether, these data indicate that the potential of Pdd to cause disease in humans is an accidental condition rather than a selected trait, and that human body temperature constitutes a stressful condition for Pdd. This study provides the first transcriptome profile of Pdd exposed at human body temperature, and unveils a number of candidate molecular targets for prevention and control of human infections caused by this pathogen.

RESUMEN

INTRODUCTION: The hypothesis of an association between papillary thyroid carcinoma (PTC) and chronic lymphocytic thyroiditis (CLT) continues to generate debate. Retrospective studies suggest that there is a greater probability of diagnosing a PTC in surgical specimens with CLT; however, prospective studies suggest that there is no true increase in risk. METHODS: An analytical, cross-section measurement and retrospective study was carried out considering gender, age and diagnosis of CLT and PTC in surgical specimens. A binary logistic regression model was proposed to predict the probability of carrying out the diagnosis of PTC based on the diagnosis of CLT, gender and age. RESULTS: The study population consisted of 1136 patients, 1047 (92.2%) women and 89 (7.8%) men, with an average age of 47.5±14.3 years. The prevalence of CLT and PTC was 14.9% and 16.1% respectively. Coexistence between PTC and CLT was found in 44 patients, corresponding to 3.9% of the population. Our logistic regression model suggests that the probability of diagnosing PTC in surgical specimens of male patients under 40 years old and with CLT is 53.8%. CONCLUSIONS: We suggest that there is a greater probability of diagnosing PTC in surgical specimens with confirmatory histological data for CLT; in addition, in males under 40 years old this probability increases.

Asunto(s)