Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication and pathogenicity.

G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibits stress granule assembly and interacts with G3BP1/2 via an ITFG motif, including residue F17, in the N protein. Prior studies examining the impact of the G3PB1-N interaction on SARS-CoV-2 replication have produced inconsistent findings, and the role of this interaction in pathogenesis is unknown. Here, we use structural and biochemical analyses to define the residues required for G3BP1-N interaction and structure-guided mutagenesis to selectively disrupt this interaction. We find that N-F17A mutation causes highly specific loss of interaction with G3BP1/2. SARS-CoV-2 N-F17A fails to inhibit stress granule assembly in cells, has decreased viral replication, and causes decreased pathology in vivo. Further mechanistic studies indicate that the N-F17-mediated G3BP1-N interaction promotes infection by limiting sequestration of viral genomic RNA (gRNA) into stress granules.

The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions.

Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.

Loss-of-function mutation in Omicron variants reduces spike protein expression and attenuates SARS-CoV-2 infection.

SARS-CoV-2 Omicron variants emerged in 2022 with >30 novel amino acid mutations in the spike protein alone. While most studies focus on receptor binding domain changes, mutations in the C-terminus of S1 (CTS1), adjacent to the furin cleavage site, have largely been ignored. In this study, we examined three Omicron mutations in CTS1: H655Y, N679K, and P681H. Generating a SARS-CoV-2 triple mutant (YKH), we found that the mutant increased spike processing, consistent with prior reports for H655Y and P681H individually. Next, we generated a single N679K mutant, finding reduced viral replication in vitro and less disease in vivo. Mechanistically, the N679K mutant had reduced spike protein in purified virions compared to wild-type; spike protein decreases were further exacerbated in infected cell lysates. Importantly, exogenous spike expression also revealed that N679K reduced overall spike protein yield independent of infection. Although a loss-of-function mutation, transmission competition demonstrated that N679K had a replication advantage in the upper airway over wild-type SARS-CoV-2 in hamsters, potentially impacting transmissibility. Together, the data show that N679K reduces overall spike protein levels during Omicron infection, which has important implications for infection, immunity, and transmission.

SARS-CoV-2 Uses Nonstructural Protein 16 to Evade Restriction by IFIT1 and IFIT3.

Understanding the molecular basis of innate immune evasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important consideration for designing the next wave of therapeutics. Here, we investigate the role of the nonstructural protein 16 (NSP16) of SARS-CoV-2 in infection and pathogenesis. NSP16, a ribonucleoside 2'- O methyltransferase (MTase), catalyzes the transfer of a methyl group to mRNA as part of the capping process. Based on observations with other CoVs, we hypothesized that NSP16 2'- O MTase function protects SARS-CoV-2 from cap-sensing host restriction. Therefore, we engineered SARS-CoV-2 with a mutation that disrupts a conserved residue in the active site of NSP16. We subsequently show that this mutant is attenuated both in vitro and in vivo , using a hamster model of SARS-CoV-2 infection. Mechanistically, we confirm that the NSP16 mutant is more sensitive to type I interferon (IFN-I) in vitro . Furthermore, silencing IFIT1 or IFIT3, IFN-stimulated genes that sense a lack of 2'- O methylation, partially restores fitness to the NSP16 mutant. Finally, we demonstrate that sinefungin, a methyltransferase inhibitor that binds the catalytic site of NSP16, sensitizes wild-type SARS-CoV-2 to IFN-I treatment. Overall, our findings highlight the importance of SARS-CoV-2 NSP16 in evading host innate immunity and suggest a possible target for future antiviral therapies. Importance: Similar to other coronaviruses, disruption of SARS-CoV-2 NSP16 function attenuates viral replication in a type I interferon-dependent manner. In vivo , our results show reduced disease and viral replication at late times in the hamster lung, but an earlier titer deficit for the NSP16 mutant (dNSP16) in the upper airway. In addition, our results confirm a role for IFIT1, but also demonstrate the necessity of IFIT3 in mediating dNSP16 attenuation. Finally, we show that targeting NSP16 activity with a 2'- O methyltransferase inhibitor in combination with type I interferon offers a novel avenue for antiviral development.

Estudio retrospectivo en pacientes con Cáncer de Colon etapa III. ¿El tratamiento adyuvante es iniciado de forma oportuna?

Introducción: En Chile, el Cáncer colorrectal (CC) abarca el 11,5% de todas las neoplasias malignas. La cirugía es la piedra angular del tratamiento del cáncer de colon, y en pacientes en etapa III, la quimioterapia adyuvante forma parte del tratamiento estándar. Materiales y Métodos: Estudio descriptivo retrospectivo transversal, de centro único, de pacientes con cáncer de colon en estadio III patológico. Objetivo principal de este estudio es conocer si, en pacientes con cáncer de colon etapa III, la quimioterapia adyuvante se entrega de manera oportuna. Resultados: En el período comprendido entre abril de 2016 y abril de 2021 se operaron 35 pacientes con cáncer de colon en estadio III patológico. Se realizó quimioterapia adyuvante en un 80%, y en siete pacientes durante las primeras ocho semanas poscirugía. La dehiscencia de anastomosis ocurrió en un 11,4%, aumentando la mediana de hospitalización en 2,2 veces. Discusión: En nuestro estudio, la adyuvancia en cáncer de colon etapa III se administró a un alto porcentaje de los pacientes (80%), pero observamos un retraso importante, ya que sólo en un 25% se inició el tratamiento durante las primeras 8 semanas poscirugía, lo cual puede ser explicado por múltiples factores, siendo la dehiscencia de anastomosis un punto importante a considerar. Conclusión: En estadio III de CC la adyuvancia puede verse retrasada por múltiples factores, lo que puede repercutir en la sobrevida de los pacientes, por lo tanto, conocer las causas de este retraso podría ayudar a instaurar nuevas estrategias, como la neoadyuvancia, para mejorar los resultados oncológicos.

Introduction: In Chile, colorectal cancer covers 11.5% of all malignant neoplasms. Surgery is the cor- nerstone of colon cancer treatment and in stage III patients adjuvant chemotherapy is part of standard treatment. Materials and Methods: A descriptive, retrospective, cross-sectional study, single center, of patients with pathological stage III colon cancer. Main objective of this study is to know if in patients with stage III colon cancer adjuvant chemotherapy is delivered in a timely manner. Results: Between April 2016 and April 2021, 35 patients with pathological stage III colon cancer were operated on. Adjuvant chemotherapy was performed in 80%, and in seven patient during the first eight weeks after surgery. Anastomotic dehiscence occurred in 11.4%, the median hospitalization increased by 2.2 times. Discussion: In this study, adjuvant stage III colon cancer was administered to a high percentage of patients (80%), but we observed a significant delay, since only 25% began treatment during the first 8 weeks post-surgery, which can be explained by multiple factors, with anastomotic dehiscence being an important point to consider. Conclusion: In stage III CC, adjuvant treatment can be delayed by multiple factors, which may affect patient survival; therefore, knowing the causes of this delay could help to establish new strategies, such as neoadjuvant therapy, to improve oncological results.

QTQTN motif upstream of the furin-cleavage site plays a key role in SARS-CoV-2 infection and pathogenesis.

The furin cleavage site (FCS), an unusual feature in the SARS-CoV-2 spike protein, has been spotlighted as a factor key to facilitating infection and pathogenesis by increasing spike processing. Similarly, the QTQTN motif directly upstream of the FCS is also an unusual feature for group 2B coronaviruses (CoVs). The QTQTN deletion has consistently been observed in in vitro cultured virus stocks and some clinical isolates. To determine whether the QTQTN motif is critical to SARS-CoV-2 replication and pathogenesis, we generated a mutant deleting the QTQTN motif (ΔQTQTN). Here, we report that the QTQTN deletion attenuates viral replication in respiratory cells in vitro and attenuates disease in vivo. The deletion results in a shortened, more rigid peptide loop that contains the FCS and is less accessible to host proteases, such as TMPRSS2. Thus, the deletion reduced the efficiency of spike processing and attenuates SARS-CoV-2 infection. Importantly, the QTQTN motif also contains residues that are glycosylated, and disruption of its glycosylation also attenuates virus replication in a TMPRSS2-dependent manner. Together, our results reveal that three aspects of the S1/S2 cleavage site-the FCS, loop length, and glycosylation-are required for efficient SARS-CoV-2 replication and pathogenesis.

Features of inhalant allergy on nasal endoscopy: a systematic review and meta-analysis.

BACKGROUND: Nasal endoscopy is increasingly accessible to ENT surgeons. The characteristics of the allergic upper airway are not well recognised. METHODOLOGY: MEDLINE (1946-2021), EMBASE (1974-2021), and the Cochrane Library were searched on 16th November 2021 to identify articles that reported endoscopic findings of patients with documented allergy who had undergone nasal endoscopy. The review followed the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. Meta-analysis was performed by pooling sensitivities and specificities using the hierarchical summary receiver operating characteristics model. RESULTS: A total of 4108 articles were identified, of which 15 manuscripts met the inclusion criteria. The included studies involved 4660 patients who had undergone nasal endoscopy. Middle turbinate (diffuse/polypoid) oedema (sensitivity 58.0%, specificity 84.5%), watery secretions (sensitivity 65.7%, specificity 76.5%), inferior turbinate hypertrophy (sensitivity 86.2%, specificity 32.2%), and unspecified turbinate hypertrophy (sensitivity 82.0%, specificity 42.9%) were identified as the features with the highest predictive value of inhalant allergy. CONCLUSIONS: Diffuse or polypoid oedema of the middle turbinate or watery secretions seen on nasal endoscopy can be a useful adjunct in the identification and diagnosis of inhalant allergy. These clinical features should be part of the diagnostic workup for patients that includes a clinical history and surrogate markers of allergic sensitisation from the skin and serum.

Encoding mu-opioid receptor biased agonism with interaction fingerprints.

Opioids are potent painkillers, however, their therapeutic use requires close medical monitoring to diminish the risk of severe adverse effects. The G-protein biased agonists of the µ-opioid receptor (MOR) have shown safer therapeutic profiles than non-biased ligands. In this work, we performed extensive all-atom molecular dynamics simulations of two markedly biased ligands and a balanced reference molecule. From those simulations, we identified a protein-ligand interaction fingerprint that characterizes biased ligands. Then, we built and virtually screened a database containing 68,740 ligands with proven or potential GPCR agonistic activity. Exemplary molecules that fulfill the interacting pattern for biased agonism are showcased, illustrating the usefulness of this work for the search of biased MOR ligands and how this contributes to the understanding of MOR biased signaling.

Modification of Oxalis tuberosa starch with OSA, characterization and application in food-grade Pickering emulsions.

The emulsifying properties of Oxalis tuberosa starch (native and chemically modified) were evaluated in Pickering emulsions based on the emulsification index, emulsion stability over time and emulsion morphology. The best conditions of chemical modification were found by esterification of starch with octenyl succinic anhydride (OSA) at a concentration of 3% and a reaction time of 2 h, achieving a degree of substitution of 0.033 ± 0.001. The results obtained using Fourier-transform infrared spectroscopy, a Rapid Visco Analyzer, and differential scanning calorimetry, indicated that the starch underwent a change in its structure and that the insertion of the OSA groups was achieved. The amphipathic characteristics of OSA starch were evaluated by forming oil-in-water emulsions. Various concentrations of OSA-starch granules (1, 2.5 and 5 wt%) were used. A higher concentration of particles produced a smaller droplet size of emulsions (76.5 ± 0.9 µm) compared to those formed at a lower concentration of 1% (92.5 ± 1.0 µm). Therefore, the starch modified with OSA displayed the necessary characteristics to be adsorbed at the oil-water interface, achieving Pickering emulsion stabilization.

Effect of voltage and oxygen on inactivation of E. coli and S. typhi using pulsed dielectric barrier discharge.

This work presents the study of the voltage and oxygen effect on bacterial inactivation in water using a pulsed dielectric barrier discharge (DBD) under atmospheric pressure, where Escherichia coli (E. coli) and Salmonella typhi (S. typhi) bacteria were used as model microorganisms. A cylindrical DBD reactor was developed and tested in applications to assay the efficiency of bacterial inactivation in water on a volume of 500 mL flowing continuously throughout the system assisted with a peristaltic pump at 4.4 ± 0.1 mL/s. The efficiency of the treatment reached a 6-log10 reduction for both E. coli and S. typhi bacteria at 106 CFU/mL of concentration at the end of the first cycle of treatment at a minimum voltage of 12 kV with oxygen bubbling gas, concluding that there was a minimum voltage to produce inactivation of E. coli and S. typhi samples. Bacterial inactivation without the oxygen condition contrasted with the high rate of inactivation with oxygen at relatively low voltage discharges.

DARK Classics in Chemical Neuroscience: Salvinorin A.

Salvinorin A is the main bioactive compound in Salvia divinorum, an endemic plant with ancestral use by the inhabitants of the Mazateca mountain range (Sierra Mazateca) in Oaxaca, México. The main use of la pastora, as locally known, is in spiritual rites due to its extraordinary hallucinogenic effects. Being the first known nonalkaloidal opioid-mediated psychotropic molecule, salvinorin A set new research areas in neuroscience. The absence of a protonated amine group, common to all previously known opioids, results in a fast metabolism with the concomitant fast elimination and swift loss of activity. The worldwide spread and psychotropic effects of salvinorin A account for its misuse and classification as a drug of abuse. Consequently, salvinorin A and Salvia divinorum are now banned in many countries. Several synthetic efforts have been focused on the improvement of physicochemical and biological properties of salvinorin A: from total synthesis to hundreds of analogues. In this Review, we discuss the impact of salvinorin A in chemistry and neuroscience covering the historical relevance, isolation from natural sources, synthetic efforts, and pharmacological and safety profiles. Altogether, the chemistry behind and the taboo that encloses salvinorin A makes it one of the most exquisite naturally occurring drugs.

Compromiso cardiaco en distrofias musculares: a propósito de un caso / Cardiac involvement in muscular dystrophies: a clinical case

Resumen Para las distrofias musculares no miotónicas como la Distrofia de Duchenne y la Distrofia de Becker, la cardiopatía forma parte inherente de su espectro clínico. La expresión clínica de éstas se puede manifestar con insuficiencia cardíaca des- compensada, arritmias o muerte súbita; gran parte de ellos cursan asintomáticos en el transcurso del tiempo, pero cuando se manifiestan constituyen una de las principales causas de muerte en estos pacientes, por lo que su detección temprana y tratamiento óptimo influyen en gran medida en el pronóstico clínico de estos pacientes. A continuación, se presenta el caso de un paciente en quien se encontró de forma incidental el compromiso cardíaco de uno de estos desórdenes neuromusculares.

Abstract Cardiac involvement in muscular dystrophies: a clinical case For non-myotonic muscular dystrophies such as Duchenne Dystrophy and Becker Dystrophy, heart disease is an inherent part of its clinical spectrum. The clinical expression of these diseases can be manifested with decompensated heart failure, arrhythmias or sudden death; A large part of them are asymptomatic over time, but when they manifest they constitute one of the main causes of death in these patients, so their early detection and optimal treatment greatly influence the clinical prognosis of these patients. The following is the case of a patient in whom the cardiac involvement of one of these neuromuscular disorders was found incidentally.

La enfermedad renal crónica en los niños y su calidad de vida; un reto para los trabajadores de salud / Chronic kidney disease in children and their quality of life; a challenge for health workers

OBJETIVO: identificar la calidad de vida de los niños de 8 a 18 años, con diagnóstico de enfermedad renal crónica, en una institución de salud de la ciudad de Bogotá. MATERIALES y MÉTODO: se llevó a cabo un estudio descriptivo de corte transversal con una población de estudio de 62 niños con diagnóstico de enfermedad renal crónica que asistieron a la consulta de nefrología pediátrica utilizando el instrumento KIDSCREEN 27. RESULTADOS: se analizaron cinco dimensiones, donde cada una tuvo un puntaje ponderado mayor a 70, que se relaciona con una buena calidad de vida; la dimensión con menor puntaje, la de actividad física, tuvo un puntaje de 70,1, seguida por la de apoyo social y amigos. CONCLUSIONES: En el grupo de estudio se encontró alterada la calidad de en la dimensión de actividad física y apoyo social y amigos; se debe tener en cuenta que, el que los niños no se sientan enfermos puede generar también riesgo para su adherencia al tratamiento. Se necesita diseñar programas que permitan realizar seguimiento y apoyo a los niños, niñas y adolescentes, pero estos deben ser novedosos y atractivos. Es indispensable que el personal de salud se prepare para poder respuesta a las demandas de los niños con enfermedades crónicas con el fin de contribuir a que ellos y sus familias tengan una buena calidad de vida.

OBJECTIVE: to identify the quality of life of children from 8 to 18 years old, diagnosed with chronic kidney disease, in a health institution in the city of Bogotá. MATERIALS AND METHOD: a descriptive cross-sectional study was conducted with a study population of 62 children diagnosed with chronic kidney disease who attended the pediatric nephrology clinic using the KIDSCREEN 27 instrument. RESULTS: five dimensions were analyzed, where each had a weighted score greater than 70, which is related to a good quality of life; the dimension with the lowest score, that of physical activity, had a score of 70.1, followed by that of social support and friends. CONCLUSIONS: chronic kidney disease can alter the quality of life, however in the study group the quality of life was not altered but its score in physical activity and social support and friends evidences the need to improve these aspects; it should be borne in mind that the fact that children do not feel sick can also generate risk for their adherence to treatment. Programs need to be designed to monitor and support children and adolescents, but these must be novel and attractive. It is essential that health personnel prepare to be able to respond to the demands of children with chronic diseases in order to contribute to ensuring that they and their families have a good quality of life

Optimizing PCR Detection of West Nile Virus from Body Fluid Specimens to Delineate Natural History in an Infected Human Cohort.

West Nile virus (WNV), a mosquito-borne arbovirus, remains a major global health concern. In this study, we optimized PCR methods then assessed serially-collected whole blood (WB), urine (UR), saliva, and semen specimens from a large cohort of WNV-positive participants to evaluate the natural history of infection and persistent shedding of WNV RNA. Viral RNA extraction protocols for frozen WB and UR specimens were optimized and validated through spiking experiments to maximize recovery of viral RNA from archived specimens and to assess the degradation of WNV RNA in stored UR specimens. The resultant procedures were used in conjunction with PCR detection to identify WNV-positive specimens and to quantify their viral loads. A total of 59 of 352 WB, 10 of 38 UR, and 2 of 34 saliva specimens tested positive for WNV RNA. Although a single semen specimen was positive 22 days post onset, we could not definitively confirm the presence of WNV RNA in the remaining specimens. WNV RNA-positive UR specimens exhibited profound loss of viral RNA during storage, highlighting the need for optimal preservation pre-storage. This study provides optimized methods for WNV RNA detection among different fluid types and offers alternative options for diagnostic testing during the acute stages of WNV.

Phenotypic and Genotypic Characterization of West Nile Virus Isolate 2004Hou3.

West Nile virus (WNV) is an arbovirus with important public health implications globally. This study characterizes a viral isolate, 2004Hou3, in comparison with the NY99 strain from the original WNV outbreak in New York, USA. NextGen sequencing was used to compare the viral isolates genetically, while wild-type C57/BL6 mice were used to compare pathogenicity and viral persistence. Significant differences in survival and clinical presentations were noted, with minor genetic variations between the two strains potentially offering an explanation. One notable difference is that 5 of 35 mice infected with the 2004Hou3 strain developed hind limb flaccid paralysis, suggesting its possible use as a small animal pathogenesis model for this clinical characteristic often observed in human WN neuroinvasive disease patients but not reported in other animal models of infection. Overall, this study suggests that 2004Hou3 is a less pathogenic strain with potential for use in long-term outcome studies using small animal models.

Efectos de la dexmedetomidina en el tratamiento del síndrome de abstinencia por enfermedad adictiva / The effects of dexmedetomidine for the treatment of abstinence syndrome secondary to addictive disease

El manejo del síndrome de abstinencia está relacionada con cambios cardiovasculares y síntomas disautonómicos que dificultan el tratamiento. La dexmedetomidina es una opción por tener mejor perfil de seguridad. El objetivo de este estudio es describir el grado de agitación y comportamiento cardiorespiratorio de los pacientes con síndrome de abstinencia por enfermedad adictiva manejados con infusión de dexmedetomidina. Estudio de cohorte retrospectivo, se incluyeron pacientes con enfermedad adictiva en proceso de desintoxicación manejados en unidad de cuidados intensivos con infusión de dexmedetomidina. Se realizó un análisis de supervivencia para determinar el tiempo a control del evento con estratificación por el tipo de sustancia y comportamiento cardiovascular. Se incluyeron 83 pacientes, 71 (85,5%) de sexo masculino, con edad mediana de 29 años (RIQ 25-36). Las principales sustancias primarias de adicción fueron heroína (n=25), basuco (n=16) y cannabinoides (n=15). La causa principal de ingreso a unidad de cuidados intensivos fue la disautonomía (n=47). El análisis de supervivencia mostró que se logró el control de la agitación al octavo día en 75% de los pacientes, con un control al quinto día mayor para el grupo opioides-cannabinoides (60%) vs alcohol-benzodiacepinas (20%). El 31,6% presentaron bradicardias asintomáticas durante la infusión de dexmedetomidina. La dexmedetomidina resultó ser un fármaco útil y seguro para controlar la agitación en pacientes con síndrome de abstinencia. Los resultados fueron diferentes en los grupos de cannabinoides y derivados del basuco y los de alcohol y benzodiacepinas. Los efectos cardiovasculares en los pacientes evaluados no requirieron soporte hemodinámico adicional

The management of abstinence syndrome is associated with cardiovascular derangements and autonomic symptoms making treatment difficult. Dexmedetomidine is an option because of a beneficial safety profile. To describe the degree of agitation and cardiorespiratory behavior of patients with abstinence syndrome secondary to addictive disease managed with an infusion of dexmedetomidine. Retrospective cohort study, patients with additive disease were included during the phase of detoxification treatment managed in the intensive care unit with dexmedetomidine infusion. A survival analysis was carried out to determine the time to symptom control stratified by type of substance and cardiovascular behavior. A total of 83 patients were included, 71 (85,5%) were male sex, median age of 29 years (IQR 25-36). The primary substances were heroin (n=25), basuco (n=16) and cannabinoids (n=15). The most frequent cause of admission to intensive care was dysautonomia (n=47). Survival analysis showed that control of agitation was achieved on the fifth day for the group opioid-cannabinoids (60%) vs. alcohol-benzodiazepines (20%). Bradycardia occurred in 31,6% of patients during dexmedetomidine infusion. Dexmedetomine resulted to be a useful and safe drug to control agitation in patients with abstinence syndrome. The results were different between the groups cannabinoids and basuco derivatives and those for alcohol and benzodiazepines. The cardiovascular effects in the studied patients did not prompt additional hemodynamic support

Función del profesional en enfermería en la atención del acoso escolar en niños, niñas y adolescentes / Role of the nursing professional in the attention of bullying in children and adolescents / Papel do profissional de enfermagem na atenção do bullying em crianças e adolescentes

Actualmente se ha incrementado y visualizado el fenómeno del acoso escolar o bullying (por su traducción al inglés); sin embargo,\r\nllama la atención que esta práctica ha existido durante mucho tiempo, pero solo ahora se evidencian las consecuencias que genera\r\nen los niños, niñas y adolescentes; además, según diversos estudios, puede conducir a suicidios en esta población. Diversas profesiones\r\nhan profundizado en el tema; a pesar de ello, no se ha visto avance en el manejo y prevención del acoso, y ha aumentado\r\nel número de casos que llegan a instituciones de salud relacionados con los daños físicos y psicológicos en quienes lo padecen.\r\nPara la enfermería es un reto poder abordar esta situación y proponer estrategias de intervención para su manejo y prevención no\r\nsolo en la víctima y victimario, sino también en la familia, las escuelas e instituciones de salud en los diferentes niveles de atención,\r\nya que cuenta con las herramientas para diseñar intervenciones en el manejo de la comunidad y del paciente institucionalizado.

Currently the phenomenon of bullying has increased and\r\nvisualized, however, it is striking that this practice has existed\r\nfor a long time, but it is up until now where the consequences\r\nthat it generates in the children and adolescents are shown,\r\nwhere, according to various studies, can generate suicides in\r\nthis population. Various professions have deepened the issue;\r\ndespite this, there has not been progress in the management\r\nand prevention of harassment and it has increased\r\nthe number of cases that reach health institutions related to\r\nphysical and psychological damage that are caused in the\r\nchild victim of bullying. It is a challenge for nursing to tackle\r\nthis situation and propose possible intervention strategies for\r\nits management and prevention, not only in the victim and\r\nvictimizer, but also in the family, schools, and health institutions\r\nin the different levels of care, since it has the tools to\r\ndesign interventions in the management of the community\r\nand the institutionalized patient.

Atualmente, o fenômeno do bullying está cada vez maior e\r\nvisível; no entanto, é impressionante que esta prática exista\r\nhá muito tempo, mas só agora que suas consequências em\r\ncrianças e adolescentes que, de acordo com vários estudos\r\npodem gerar suicídios nesta população, estão evidentes. Várias\r\nprofissões se aprofundaram no assunto. Porém, não houve\r\nprogresso na gestão e prevenção de assédio e o número de\r\ncasos que chegam a instituições de saúde relacionados ao\r\ndano físico e psicológico causado à criança vítima de assédio\r\nescolar aumentou. É um desafio para a enfermagem abordar\r\nesta situação e propor possíveis estratégias de intervenção\r\npara a sua gestão e prevenção, não só na vítima e perpetrador,\r\nmas também na família, escolas e instituições de saúde nos\r\ndiferentes níveis de cuidados, uma vez que tem as ferramentas\r\npara conceber intervenções no manejo da comunidade e do\r\npaciente institucionalizado.

Exploring the cancer caregiver's journey through web-based Meaning-Centered Psychotherapy.

OBJECTIVE: Psychosocial interventions are historically underutilized by cancer caregivers, but support programs delivered flexibly over the Internet address multiple barriers to care. We adapted Meaning-Centered Psychotherapy for cancer caregivers, an in-person psychotherapeutic intervention intended to augment caregivers' sense of meaning and purpose and ameliorate burden, for delivery in a self-administered web-based program, the Care for the Cancer Caregiver (CCC) Workshop. The present study evaluated the feasibility, acceptability, and preliminary effects of this program. METHODS: Eighty-four caregivers were randomized to the CCC Workshop or waitlist control arm. Quantitative assessments of meaning, burden, anxiety, depression, benefit finding, and spiritual well-being were conducted preintervention (T1), within 2-weeks postintervention (T2), and 2- to 3-month follow-up (T3). In-depth semistructured interviews were conducted with a subset of participants. RESULTS: Forty-two caregivers were randomized to the CCC Workshop. Attrition was moderate at T2 and T3, with caregiver burden and bereavement as key causes of drop-out. At T2 and T3, some observed mean change scores and effect sizes were consistent with hypothesized trends (eg, meaning in caregiving, benefit finding, and depressive symptomatology), though no pre-post significant differences emerged between groups. However, a longitudinal mixed-effects model found significant differential increases in benefit finding in favor of the CCC arm. CONCLUSIONS: The CCC Workshop was feasible and acceptable. Based on effect sizes reported here, a larger study will likely establish the efficacy of the CCC Workshop, which has the potential to address unmet needs of caregivers who underutilize in-person supportive care services.

Plasmid pUM505 encodes a Toxin-Antitoxin system conferring plasmid stability and increased Pseudomonas aeruginosa virulence.

Pseudomonas aeruginosa plasmid pUM505 possesses a pathogenicity island that contains the pumAB genes that encode products with sequence similarity to Toxin-Antitoxin (TA) modules. RT-PCR assays on the overlapping regions of the pumAB genes generated a bicistronic messenger RNA, suggesting that they form an operon. When the pumAB genes were cloned into the pJET vector, recombinant plasmid pJET-pumAB was maintained under nonselective conditions in Escherichia coli cells after six daily subcultures, whereas pJET without pumAB genes was lost. These data indicate that pumAB genes confer post-segregational plasmid stability. In addition, overexpression of the PumA protein in the E. coli BL21 strain resulted in a significant growth inhibition, while BL21 co-expressing the PumA and PumB proteins did not show growth inhibition. These results indicate that pumAB genes encode a TA system where the PumB protein counters the toxic effects of the PumA toxin. Furthermore, P. aeruginosa PAO1 transformants with the pumA gene increased Caenorhabditis elegans and mouse mortality rate and improved mouse organ invasion, effects neutralized by the PumB protein. Moreover, purified recombinant His-PumA protein decreased the viability of C. elegans, indicating that the PumA protein could acts as a toxin. These results indicate that PumA has the potential to promoter the PAO1 virulence against C. elegans and mice when is expressed in absence of PumB. This is the first description, to our knowledge, of a plasmid-encoded TA system that confers plasmid stability and encoded a toxin with the possible ability to increase the P. aeruginosa virulence.

Airflow and symptom outcomes between allergic and non-allergic rhinitis patients from turbinoplasty.

BACKGROUND: Inferior turbinate procedures are applied to relieve medically refractory nasal obstruction. However, the nature of congestion differs between allergic(AR) and non-allergic rhinitis(NAR). This study compares surgical outcomes between AR and NAR patients. METHODOLOGY: A case-control study of patients undergoing turbinate with or without septoplasty surgery for nasal obstruction was performed. Patient reported outcomes were: nasal obstruction, global nasal function(GNF), and sino-nasal outcome test(SNOT-22) with rhinitis, facial symptom, sleep and psychological sub-scores. Nasal peak inspiratory flow(NPIF) assessed nasal airflow. Measurements were obtained preoperatively and 3 months postoperatively. RESULTS: 190 patients were assessed. AR had worse obstruction and worse GNF. All outcomes improved post-surgery; nasal obstruction, GNF, SNOT-22, rhinitis-symptoms, facial-symptoms, sleep-function, psychological-function and NPIF. GNF improvement was greater in AR. NPIF improvement was similar between groups. CONCLUSIONS: Both AR and NAR patients gained benefit from surgery to relieve nasal obstruction. AR patients demonstrate greater improvement in GNF score but allergy management may contribute to this.