Despite occurring at the microscopic scale, the armed race between phages and their bacterial hosts involves multiple mechanisms, some of which are just starting to be understood. On the one hand, ...bacteria have evolved strategies that can stop the viral infection at different stages (adsorption, DNA injection and replication, biosynthesis and assembly of the viral progeny and/or release of the newly formed virions); on the other, phages have gradually evolved counterattack strategies that allow them to continue infecting their prey. This co-evolutionary process has played a major role in the development of microbial populations in both natural and man-made environments. Notably, understanding the parameters of this microscopic war will be paramount to fully benefit from the application of phage therapy against dangerous, antibiotic-resistant human pathogens. This review gathers the current knowledge regarding the mechanisms of phage resistance in the
genus, which includes
, one of the most concerning microorganisms in terms of antibiotic resistance acquisition. Some of these strategies involve permanent changes to the bacterial cell via mutations, while others are transient, adaptive changes whose expression depends on certain environmental cues or the growth phase. Finally, we discuss the most plausible strategies to limit the impact of phage resistance on therapy, with a special emphasis on the importance of a rational design of phage cocktails in order to thwart therapeutic failure.
Infections by the pathogen
currently represent one of the most serious threats to human health worldwide, especially due to the production of enterotoxins and the ability to form biofilms. These ...structures and the acquisition of antibiotic resistance limit the action of antibiotics and disinfectants used to combat this microorganism in the industry and the clinic.
This work reports a comparative phenotypic and genotypic study of 18
strains from different origins: clinical samples, milk from mastitic cows and food industry surfaces, most of which were isolated in Northern Spain.
Genetically, the strains were very diverse but, in most cases, a closer proximity was observed for those from the same source. Notably, the average number of virulence genes was not significantly different in strains from the food sector. Of the 18 strains, 10 coded for at least one enterotoxin, and four of them carried 6 or 7 enterotoxin genes. The latter were all veterinary or clinical isolates. Most strains carried prophages, plasmids and/or pathogenicity islands. Regarding antibiotic resistance, although phenotypically all strains showed resistance to at least one antibiotic, resistance genes were only identified in 44.5% of strains, being mastitis isolates those with the lowest prevalence. Virulence-related phenotypic properties such as haemolytic activity, staphyloxanthin production, biofilm-forming capacity and spreading ability were widely distributed amongst the isolates.
Our results indicate that production of virulence factors, antibiotic resistance and biofilm formation can be found in
isolates from diverse environments, including the food industry, although some of these traits are more prevalent in strains isolated from infections in cows or humans. This emphasizes on the importance of monitoring the spread of these determinants not only in samples from the clinical environment, but also along the food chain, a strategy that falls under the prism of a one-health approach.
Cellular antiviral programs encode molecules capable of targeting multiple steps in the virus lifecycle. Zinc-finger antiviral protein (ZAP) is a central and general regulator of antiviral activity ...that targets pathogen mRNA stability and translation. ZAP is diffusely cytoplasmic, but upon infection ZAP is targeted to particular cytoplasmic structures, termed stress granules (SGs). However, it remains unclear if ZAP's antiviral activity correlates with SG localization, and what molecular cues are required to induce this localization event. Here, we use Sindbis virus (SINV) as a model infection and find that ZAP's localization to SGs can be transient. Sometimes no apparent viral infection follows ZAP SG localization but ZAP SG localization always precedes accumulation of SINV non-structural protein, suggesting virus replication processes trigger SG formation and ZAP recruitment. Data from single-molecule RNA FISH corroborates this finding as the majority of cells with ZAP localization in SGs contain low levels of viral RNA. Furthermore, ZAP recruitment to SGs occurred in ZAP-expressing cells when co-cultured with cells replicating full-length SINV, but not when co-cultured with cells replicating a SINV replicon. ZAP recruitment to SGs is functionally important as a panel of alanine ZAP mutants indicate that the anti-SINV activity is correlated with ZAP's ability to localize to SGs. As ZAP is a central component of the cellular antiviral programs, these data provide further evidence that SGs are an important cytoplasmic antiviral hub. These findings provide insight into how antiviral components are regulated upon virus infection to inhibit virus spread.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV) are spread by mosquitoes and cause human disease and mortality in tropical areas. In contrast, Powassan virus ...(POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito-borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics.
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•Sera from Mexico and Brazil neutralize POWV and TBEV, which are not known to circulate there•Monoclonal antibody P014 binds to POWV but not to endemic flaviviruses•Monoclonal antibodies P002 and P003 neutralize POWV lineage I•The P003 epitope is shared across 13 flaviviruses from tick and mosquito serocomplexes
Cervantes Rincón et al. describe antibody neutralizing activity against Powassan virus from regions of the Americas where this flavivirus transmitted by ticks is not known to circulate. Two monoclonal antibodies to the EDIII (P002 and P003) are broadly cross-reactive against tick- and mosquito-borne flaviviruses.
People differ in their sleep-wake behavior. This individual difference is conceptualized in different aspects, such as wake up times, bed times, times of peak performance, as well as in morning ...affect. A total of 14,987 visitors of an exhibition in the LWL State Museum of Natural History, Münster (Germany), did the survey on chronotype and gave their consent that these data can be used for a scientific study. Age groups were coded into 5-year bins. Mean age (mean ± SD) was 28.2 ± 17.5 years. There were 8075 females (54%) and 6912 males in the sample. The German version of the rMEQ (reduced Morningness-Eveningness-Questionnaire) was used for data collection. The data showed clear age effects. Younger children are more morning oriented and become rapidly evening oriented during puberty, while the more attenuated turn towards morningness occurs from the age of 20 years. Then between the ages 25 to 30 morningness-eveningness remained rather stable. Significant gender differences existed in the reproductive age, i.e., the age groups 20 to 50 (corresponding to the age 16–50 years). In other age groups, no gender differences could be detected. Seasonal effects were also found. Chronotype score was lowest during the summer months (and more evening oriented). Based on the single item analysis of the five questions of the rMEQ, we found age group differences in all items. Gender differences occurred in all items except item 1, which deals with the preferred wake-up time. Men always scored significantly lower (i.e. more evening oriented) than women except in item 2 (tiredness after awakening). Seasonal effects were only significant in item 3, which is related to preferred bed times. People showed a later bed time preference during summer. The classification of chronotypes according to the cut-off scores provided by Adan and Almirall (1991) and by using the 20/80 percentile provided identical cut-off scores (values of 11 and below for evening types and 18 and above for morning types).
Missed gastric cancer (MGC) is poorly documented in Mediterranean populations.
(1) To assess the rate, predictors and survival of MGC. (2) To compare MGC and non-MGC tumors.
This is a ...retrospective-cohort study conducted at four centers. MGC was defined as cancer detected within three years after negative esophagogastroduodenoscopy. Gastric adenocarcinomas diagnosed between 2008–2015 were included. Patients with no follow-up were excluded.
During the study period 123,395 esophagogastroduodenoscopies were performed, with 1374 gastric cancers being diagnosed (1.1%). A total of 1289 gastric cancers were finally included. The overall rate of MGC was 4.7% (61/1289, 3.7–6%). A negative esophagogastroduodenoscopy in MGC patients was independently associated with PPI therapy (p < 0.001), previous Billroth II anastomosis (p = 0.002), and lack of alarm symptoms (p < 0.001). The most frequent location for MGC was the gastric body(52.4%). MGCs were smaller than non-MGCs (31 vs 41 mm, p = 0.047), more often flat or depressed (p = 0.003) and less likely to be encountered as advanced disease. Overall 2-year survival was similar between MGC (34.1%) and Non-MGC (35.3 %) (p = 0.59).
MGC accounted for nearly five percent of newly-diagnosed gastric adenocarcinomas. Overall survival was poor and not different between MGC and non-MGC.
Pelvic fractures occur in up to 25% of all severely injured trauma patients and its mortality is markedly high despite advances in resuscitation and modernization of surgical techniques due to its ...inherent blood loss and associated extra-pelvic injuries. Pelvic ring volume increases significantly from fractures and/or ligament disruptions which precludes its inherent ability to self-tamponade resulting in accumulation of hemorrhage in the retroperitoneal space which inevitably leads to hemodynamic instability and the lethal diamond. Pelvic hemorrhage is mainly venous (80%) from the pre-sacral/pre-peritoneal plexus and the remaining 20% is of arterial origin (branches of the internal iliac artery). This reality can be altered via a sequential management approach that is tailored to the specific reality of the treating facility which involves a collaborative effort between orthopedic, trauma and intensive care surgeons. We propose two different management algorithms that specifically address the availability of qualified staff and existing infrastructure: one for the fully equipped trauma center and another for the very common limited resource center.
Introducción. El manejo de pacientes con cáncer gástrico está determinado por el estadio preoperatorio y requiere de una estrategia multidisciplinaria. La cirugía radical, especialmente en pacientes ...con estadios tempranos, es potencialmente curativa. El abordaje por vía laparoscópica ofrece ventajas sobre la vía abierta, sin embargo, en nuestro medio no hay información en cuanto a resultados oncológicos y posoperatorios tempranos.
Métodos. Estudio retrospectivo, descriptivo, de tipo transversal, en pacientes con cáncer gástrico llevados a gastrectomía laparoscópica con intención curativa, entre el 2014 y el 2019, en tres instituciones de la ciudad de Medellín. Se analizaron los datos demográficos, los resultados posoperatorios y oncológicos a corto plazo.
Resultados. Se incluyeron 75 pacientes sometidos a gastrectomía laparoscópica. La mediana de edad fue de 64 años y el estadio más frecuente fue el III. La gastrectomía fue subtotal en 50 pacientes (66,7 %) y total en 25 pacientes (33,3 %). Se hizo disección linfática D2 en 73 pacientes (97,3 %) con una mediana en el recuento ganglionar de 27. La tasa de resección R0 fue de 97,3 %. La mediana de estancia hospitalaria fue de seis días. La tasa de complicaciones mayores fue del 20 % y la mortalidad a 90 días fue del 4 %.
Discusión. La calidad oncológica de la gastrectomía laparoscópica fue adecuada y cumple con las recomendaciones de las guías internacionales. Si bien la morbilidad sigue siendo alta, tiene una tasa de sobrevida del 96 % a 90 días.
El año 2020 ha transformado la vida de la mayoría de los habitantes del planeta. Hace un año hubiera sido inimaginable pensar que una situación como la actual pudiera ser real y no fruto de una ...película perteneciente al género de catástrofes. Con este artículo queremos dejar constancia de la repercusión emocional e intelectual que supuso la coincidencia de la pandemia con el desarrollo de una asignatura optativa transversal para los grados de Ciencias de la Salud centrada en el uso del cine y la literatura como recursos docentes. La coincidencia temporal del inicio del confinamiento al que se vio sometida toda la población española, con el desarrollo del módulo de catástrofes y, más concretamente con el tema de las epidemias, revistió el progreso del resto de la asignatura de un ambiente especial que tal vez no volvamos a vivir, al menos con las mismas características.
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