Impact of platinum-based chemotherapy on the tumor mutational burden and immune microenvironment in non-small cell lung cancer with postoperative recurrence.

PURPOSE: To investigate the impact of platinum-based adjuvant chemotherapy on the immunotherapeutic biomarkers of postoperative recurrent tumors in non-small cell lung cancer (NSCLC). METHODS: This study involved twenty-two cases of NSCLC, all of which underwent postoperative platinum-based chemotherapy, with matched surgical samples obtained from both their primary tumors (PTs) and recurrent tumors (RTs). Multiplex immunofluorescence was performed to assess the tumor proportion score (TPS) and immune cells (IC) on whole sections. Whole exon sequencing (WES) was conducted to investigate the tumor mutational burden (TMB) and tumor neoantigen burden (TNB). RESULTS: Compared to paired PTs, RTs exhibited higher PD-L1 expression, along with a slightly elevated density of intratumoral PD-L1+ cells (p = 0.082) and an increased tumor proportion score (mean TPS: 40.51% vs. 28.56%, p = 0.046). Regarding IC infiltration, RTs generally demonstrated significantly lower CD8+ cytotoxic T lymphocyte (CTL) density (p = 0.011) and lower CD68+ macrophage density (p = 0.005), with a loss of tertiary lymphoid structure (TLS). The comparison between RTs and PTs revealed no significant differences in TMB (p = 0.795), whereas the count of TNB in RTs was notably increased compared to PTs (p = 0.033). Prognosis analysis indicated that a higher density of CD8+ CTLs in RTs was positively correlated with improved overall survival (OS). CONCLUSIONS: In NSCLC patients with a history of postoperative platinum-based chemotherapy, the RTs demonstrated a trend towards increased PD-L1 expression and TMB/TNB, but a state of immunosuppression characterized by decreased ICs and loss of TLS, which may potentially impact the therapeutic benefits of immunotherapy.

Resistance phenotype and genetic features of a heterogeneous vancomycin intermediate-resistant Staphylococcus aureus strain from an immunocompromised patient.

Strain C1 was successfully isolated from an immunosuppressed patient with persistent bacteremia, who had not previously been exposed to glycopeptide antibiotics. This strain was found to be a heterogeneous vancomycin intermediate-resistant Staphylococcus aureus (hVISA). It is noteworthy that, following a brief period of vancomycin treatment, strains C6, C8, and C9, which were obtained from blood and other body parts, exhibited a significant reduction in heterogeneity as determined by population analysis profile-area under the curve (PAP-AUC) detection. Genotyping analysis revealed that these bacterial strains belonged to the same SCCmecIVa-ST59-t437-agrI genotype and shared the same virulome and resistome. In this study, a comparative genomics analysis was conducted between strain C1 and strain N315 to identify potential hVISA-associated mutations. Ultimately, a total of 205 mutation sites in 19 candidate genes, likely associated with the hVISA phenotype, were identified.

Research hotspots and new trends in the impact of resistance training on aging, bibliometric and visual analysis based on CiteSpace and VOSviewer.

Purpose: Resistance training (RT) can intervene in aging, which can effectively improve trainees' life. However, unhealthy living habits such as irregular life, obesity and hyperlipidemia, and chronic diseases lead to a significant decline in the energy level of the population, seriously affecting the health of the population. Our research identifies the research hotspots of RT to intervene in aging from the perspective of bibliometrics, predicts research frontiers and development trends, and provides more perspectives for research on aging populations. Methods: In this study, we used CiteSpace and VOSviewer visualization software to draw the scientific knowledge map of countries/regions, institutions, authors, co-occurrence keywords, and co-cited references of published articles, and explore the Web of Science core collection database all about the RT intervention aging research status, hotspots, frontiers, and development trends of articles on aging. Results: Among the 760 articles that meet the inclusion criteria, the number of articles published and the frequency of citations have increased steadily in the past 5 years. Judging from the countries/regions, institutions, scholars, and journals that published articles, the ones with the largest numbers are the USA, Univ Estadual Londrina, Cyrino ES, and Exp Gerontol. The ones with the highest influence are England, Univ Arkansas Med Sci, Frontera WR, and Biochem Biophys Rep Co. The top five co-occurrence keywords of include exercise, strength, resistance training, skeletal muscle, and muscle strength. The research frontier is physical function. Conclusion: In the field of RT intervention aging research, relevant scholars deserve further in-depth research and exploration. The United States, Brazil, Canada, and other economically developed countries/regions, institutions, and authors have greater influence and productivity. These quantitative research results can provide references for relevant scholars' follow-up research and government departments to formulate and modify health policies or measures.

Thoracic aortic reactivity in obese patients submitted to aerobic exercise / Reatividade da aorta torácica em pacientes obesos submetidos ao exercício aeróbico / Reactividad de la aorta torácica en pacientes obesos sometidos a ejercicio aeróbico

ABSTRACT Introduction: Aerobic exercise can improve the function of the cardiovascular circulatory system, reducing morbidity and mortality from cardiovascular disease by stimulating the production of endogenous self-protection. Activating potassium channels in vascular smooth muscle cells can cause vasodilation and increase blood flow, lowering blood pressure. There is a sensitivity to intracellular ATP and ADP concentration among the variety of potassium channels distributed in vascular smooth muscle cells, which vary mainly during aerobic physical activity. Objective: Explore the effect of aerobic exercise on the vascular reactivity of the thoracic aorta in patients with obesity and hyperlipidemia. Methods: Randomized controlled trial in twenty male Wistar rats weighing 250g and two months old. The control group remained at rest while the experimental group performed aerobic exercise on a treadmill at increasing speed for eight weeks. The rats were dissected, and dilatators and vasoconstrictors drugs stimulated their blood vessels in a tamponade solution. Observation of vascular changes was measured under controlled tensioning. Results: The blockade of KATP channels in vascular smooth muscle caused tonic contraction of vascular smooth muscle cells and increased blood pressure. Conclusion: Long-term regular aerobic exercise may induce changes in rats' thoracic aortic vascular function and vascular smooth muscle reactivity. Aerobic exercise can also significantly improve the activity of KATP channels. Evidence Level II; Therapeutic Studies - Investigating the results.

RESUMO Introdução: O exercício aeróbico pode melhorar a função do sistema circulatório cardiovascular, reduzindo a morbidade e mortalidade de doenças cardiovasculares estimulando a produção de autoproteções endógenas. A ativação de canais de potássio nas células musculares lisas vasculares pode causar vasodilatação e aumentar o fluxo sanguíneo, diminuindo a pressão sanguínea. Há uma sensível a concentração de ATP intracelular e ADP dentre a variedade de canais de potássio distribuídos em células musculares lisas vasculares, que variam principalmente durante a atividade física aeróbica. Objetivo: Explorar o efeito do exercício aeróbico na reatividade vascular da aorta torácica em pacientes com obesidade e hiperlipidemia. Métodos: Estudo randomizado controlado em vinte ratos Wistar machos de 250g e 2 meses de idade. O grupo controle permaneceu sob repouso enquanto o experimental realizava exercícios aeróbicos em esteira com velocidade crescente durante 8 semanas. Os ratos foram dissecados e seus vasos sanguíneos estimulados com drogas vasoconstritoras e dilatadoras em solução tampão. A observação das alterações vasculares foi mensurada sob tensionamento controlado. Resultados: O bloqueio dos canais KATP no músculo liso vascular causou contração tônica das células musculares lisas vasculares e aumento da pressão arterial. Conclusão: Exercícios aeróbicos regulares de longo prazo podem induzir alterações na função vascular da aorta torácica e reatividade do músculo liso vascular em ratos. O exercício aeróbico também pode melhorar significativamente a atividade dos canais KATP. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El ejercicio aeróbico puede mejorar la función del sistema circulatorio cardiovascular, reduciendo la morbilidad y la mortalidad de las enfermedades cardiovasculares al estimular la producción de autoprotección endógena. La activación de los canales de potasio en las células del músculo liso vascular puede causar vasodilatación y aumentar el flujo sanguíneo, reduciendo la presión arterial. Existe una sensibilidad a la concentración intracelular de ATP y ADP entre la variedad de canales de potasio distribuidos en las células del músculo liso vascular, que varían principalmente durante la actividad física aeróbica. Objetivo: Explorar el efecto del ejercicio aeróbico sobre la reactividad vascular de la aorta torácica en pacientes con obesidad e hiperlipidemia. Métodos: Ensayo controlado aleatorio en veinte ratas Wistar macho de 250 g y 2 meses de edad. El grupo de control permaneció en reposo mientras que el grupo experimental realizó ejercicios aeróbicos en una cinta de correr a velocidad creciente durante 8 semanas. Las ratas fueron disecadas y sus vasos sanguíneos fueron estimulados con fármacos vasoconstrictores y dilatadores en solución amortiguada. La observación de los cambios vasculares se midió bajo tensión controlada. Resultados: El bloqueo de los canales KATP en el músculo liso vascular provocó una contracción tónica de las células del músculo liso vascular y un aumento de la presión arterial. Conclusión: El ejercicio aeróbico regular a largo plazo puede inducir cambios en la función vascular de la aorta torácica y en la reactividad del músculo liso vascular en ratas. El ejercicio aeróbico también puede mejorar significativamente la actividad del canal KATP. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

The application value of CDFI and SMI combined with serological markers in distinguishing benign and malignant thyroid nodules.

PURPOSE: The purpose of this study is to explore the application value of CDFI and SMI combined with serological markers in distinguishing benign and malignant thyroid nodules. METHOD: A total of 192 patients with thyroid nodules admitted to our hospital from July 2019 to December 2020 were selected as subjects. Color Doppler blood flow imaging (CDFI) and supermicro blood flow imaging (SMI) methods are used to detect the blood flow of patients and the levels of serum thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyroid stimulating hormone (TSH). The receiver operating characteristic curve (ROC curve) was used to observe the sensitivity and specificity of serological markers for distinguishing benign and malignant thyroid nodules, and combined with CDFI and SMI to observe the sensitivity and specificity for distinguishing benign and malignant thyroid nodules. RESULTS: The levels of TgAb, TPOAb and TSH in benign thyroid nodules were lower than those of the malignant group, and the difference was statistically significant (P < 0.01). There was no statistically significant difference between benign and malignant thyroid nodules in the presence or absence of the capsule and the presence or absence of vocal halo (P > 0.05), while the differences in the nodule morphology, boundary, internal echo and internal calcification were statistically significant (P < 0.01). CONCLUSION: CDFI and SMI combined with serological index detection have higher value in the differential diagnosis of thyroid cancer, which can significantly improve the sensitivity and specificity of differential diagnosis.

Quantification of mitral regurgitation after transcatheter edge-to-edge repair: Comparison of echocardiography and patient-specific in silico models.

BACKGROUND: Doppler echocardiographic (echo) assessment of residual mitral regurgitation (MR) after transcatheter edge-to-edge repair (TEER) is challenging and often subjective. This study aimed to evaluate the accuracy and feasibility of standardized quantitative echo methods for assessment of MR severity after MitraClip repair by comparing measurements against a reference MR severity obtained from patient-specific in silico models. METHODS: Post-procedure hemodynamics were simulated under five different MitraClip configurations in previously validated patient-specific in silico models for the treatment of functional MR. The residual regurgitant volume was calculated as in clinical practice using four quantitative virtual echo methods: pulsed Doppler, volumetric, proximal isovelocity surface area (PISA) and vena contracta area (VCA). Multiple permutations were performed for each method. Virtual echo MR results were evaluated against reference MR values directly extracted from the 5 patient-specific in silico models. RESULTS: The echo methods with the greatest accuracy were the three-dimensional (3D) volumetric method (r = 0.957, bias -0.8 ± 1.2 ml, p = 0.01), the 3D VCA method wherein velocity time integrals were evaluated for each jet assessed (r = 0.919, bias -1.5 ± 1.7 ml, p = 0.03), and the 3D PISA method integrating surface areas throughout systole (r = 0.98, bias -2.0 ± 0.9 ml, p = 0.003). The pulsed Doppler and 2D volumetric methods had technical limitations that may result in a high underestimation or overestimation of the MR severity after TEER. In the case of multiple regurgitant jets, a more accurate MR assessment was obtained when all significant jets were evaluated. CONCLUSIONS: Clinically, the 3D volumetric, 3D VCA and 3D PISA methods gave the most accurate MR quantification after TEER. Three-dimensional echo technologies harbor the potential of becoming the non-invasive imaging tool of choice for MR quantification after complex transcatheter mitral interventions.

Application of lateral supraclavicular incision in unilateral thyroid papillary carcinoma surgery.

INTRODUCTION: The standard approach to thyroidectomy is a collar incision via the anterior neck, and the neck scar has always been a source of worry for patients. Acceptable wound cosmetology has become a focus for thyroid surgeons. OBJECTIVE: To verify the effectiveness and cosmetic results of thyroidectomy through a lateral supraclavicular incision. METHODS: 180 patients were randomly divided into two groups: a lateral supraclavicular approach and a conventional transcervical approach. The main outcomes included incision length, intraoperative blood loss, operative time, total drainage volume, hospitalization expense, early postoperative pain measured by visual analog scale, infection, and perceived cosmetic outcome. RESULTS: There were no statistical significances between the two groups in terms of age, gender, nodule size, intraoperative blood loss, operative time, total drainage volume, hospital expense and postoperative complications, whereas there were significant differences in terms of incision length (5.2±1.04cm vs. 6.9±1.14cm, p<0.05). CONCLUSIONS: The lateral supraclavicular incision is a safe and feasible approach for thyroidectomy. Compared with conventional approach, it provides a better cosmetic result.

Application of lateral supraclavicular incision in unilateral thyroid papillary carcinoma surgery / Incisão supraclavicular lateral em cirurgia de carcinoma papilífero unilateral de tireoide

Abstract Introduction The standard approach to thyroidectomy is a collar incision via the anterior neck, and the neck scar has always been a source of worry for patients. Acceptable wound cosmetology has become a focus for thyroid surgeons. Objective To verify the effectiveness and cosmetic results of thyroidectomy through a lateral supraclavicular incision. Methods 180 patients were randomly divided into two groups: a lateral supraclavicular approach and a conventional transcervical approach. The main outcomes included incision length, intraoperative blood loss, operative time, total drainage volume, hospitalization expense, early postoperative pain measured by visual analog scale, infection, and perceived cosmetic outcome. Results There were no statistical significances between the two groups in terms of age, gender, nodule size, intraoperative blood loss, operative time, total drainage volume, hospital expense and postoperative complications, whereas there were significant differences in terms of incision length (5.2 ± 1.04 cm vs. 6.9 ± 1.14 cm, p < 0.05). Conclusions The lateral supraclavicular incision is a safe and feasible approach for thyroidectomy. Compared with conventional approach, it provides a better cosmetic result.

Resumo Introdução A abordagem padrão para tireoidectomia é uma incisão em colar na face anterior do pescoço; a cicatriz no pescoço sempre foi uma fonte de preocupação para os pacientes; consequentemente, a cosmetologia aceitável da ferida tornou‐se um foco de atenção para os cirurgiões de cabeça e pescoço. Objetivos Verificar a eficácia e os resultados cosméticos da tireoidectomia por meio de incisão supraclavicular lateral. Método Foram divididos aleatoriamente 180 pacientes em dois grupos: um grupo supraclavicular lateral (Grupo LS) e outro transcervical convencional (Grupo TC). Os desfechos principais incluíram comprimento da incisão, perda de sangue intraoperatória, tempo cirúrgico, volume total de drenagem, despesas hospitalares, dor no pós‐operatório imediato medida através de escala visual analógica, infecção e resultado cosmético percebido. Resultados Não houve significância estatística entre os dois grupos em termos de idade, sexo, tamanho do nódulo, perda sanguínea intraoperatória, tempo cirúrgico, volume total de drenagem, custo hospitalar e complicações pós‐operatórias, mas houve diferença significante em termos de comprimento da incisão (5,2 ± 1,04 cm vs. 6,9 ± 1,14 cm, p < 0,05). Conclusão A incisão supraclavicular lateral é uma abordagem segura e viável para tireoidectomia. Em comparação com a abordagem convencional, oferece um melhor resultado cosmético.

The effects of cryopreservation on the acrosome structure, enzyme activity, motility, and fertility of bovine, ovine, and goat sperm.

The study was designed to investigate the effects of cryopreservation on bovine, ovine, and goat sperm motility, acrosome structure, enzyme activity, and fertilization ability. Percentage of sperm with hyaluronidase enzyme (HYD) activity was detected by a modified sodium hyaluronate-gelatin membrane. The N-α-benzoyl-DL-arginine-p-nitroanilide (BNPNA) method was used to assess the sperm acrosome enzyme (ACE). The mean percentage of sperm acrosome integrity dropped significantly (P < 0.01) after cryopreservation. The ACE activity of bovine sperm (100.48) was higher (P < 0.01) than that of ovine (57.88) or goat sperm (50.30), while the percentage of sperm with HYD activity of bovine (71.10%) and ovine (67.60%) sperm was higher than that of goat sperm (58.52%) after cryopreservation (P < 0.01). Sperm motility was positively correlated with the activity of the two acrosome enzymes before and after cryopreservation (P < 0.01). Cryopreservation had a negative effect on acrosomal morphology, motility, and acrosomal enzyme activity in their sperm. The fertilization ability of ovine and goat sperm decreased significantly after cryopreservation, but that of frozen bovine sperm did not differ significantly when compared with fresh sperm. There was no significant difference between ovine and goat sperm indices, except for percentage of sperm with HYD activity.

The effects of cryopreservation on the acrosome structure, enzyme activity, motility, and fertility of bovine, ovine, and goat sperm

The study was designed to investigate the effects of cryopreservation on bovine, ovine, and goat sperm motility, acrosome structure, enzyme activity, and fertilization ability. Percentage of sperm with hyaluronidase enzyme (HYD) activity was detected by a modified sodium hyaluronate-gelatin membrane. The N-α-benzoyl-DL-arginine-p-nitroanilide (BNPNA) method was used to assess the sperm acrosome enzyme (ACE). The mean percentage of sperm acrosome integrity dropped significantly (P < 0.01) after cryopreservation. The ACE activity of bovine sperm (100.48) was higher (P < 0.01) than that of ovine (57.88) or goat sperm (50.30), while the percentage of sperm with HYD activity of bovine (71.10%) and ovine (67.60%) sperm was higher than that of goat sperm (58.52%) after cryopreservation (P < 0.01). Sperm motility was positively correlated with the activity of the two acrosome enzymes before and after cryopreservation (P < 0.01). Cryopreservation had a negative effect on acrosomal morphology, motility, and acrosomal enzyme activity in their sperm. The fertilization ability of ovine and goat sperm decreased significantly after cryopreservation, but that of frozen bovine sperm did not differ significantly when compared with fresh sperm. There was no significant difference between ovine and goat sperm indices, except for percentage of sperm with HYD activity.

The effects of cryopreservation on the acrosome structure, enzyme activity, motility, and fertility of bovine, ovine, and goat sperm

The study was designed to investigate the effects of cryopreservation on bovine, ovine, and goat sperm motility, acrosome structure, enzyme activity, and fertilization ability. Percentage of sperm with hyaluronidase enzyme (HYD) activity was detected by a modified sodium hyaluronate-gelatin membrane. The N-α-benzoyl-DL-arginine-p-nitroanilide (BNPNA) method was used to assess the sperm acrosome enzyme (ACE). The mean percentage of sperm acrosome integrity dropped significantly (P < 0.01) after cryopreservation. The ACE activity of bovine sperm (100.48) was higher (P < 0.01) than that of ovine (57.88) or goat sperm (50.30), while the percentage of sperm with HYD activity of bovine (71.10%) and ovine (67.60%) sperm was higher than that of goat sperm (58.52%) after cryopreservation (P < 0.01). Sperm motility was positively correlated with the activity of the two acrosome enzymes before and after cryopreservation (P < 0.01). Cryopreservation had a negative effect on acrosomal morphology, motility, and acrosomal enzyme activity in their sperm. The fertilization ability of ovine and goat sperm decreased significantly after cryopreservation, but that of frozen bovine sperm did not differ significantly when compared with fresh sperm. There was no significant difference between ovine and goat sperm indices, except for percentage of sperm with HYD activity.(AU)

Epidemiology and outcomes of anal abscess in patients on chronic dialysis: a 14-year retrospective study.

OBJECTIVES: We conducted this retrospective study to elucidate the clinical presentation and outcomes of anal abscess in chronic dialysis patients. METHODS: We performed a chart review of patients who were hospitalized for anal abscess from Jan. 2002 to Dec. 2015. A total of 3,074 episodes of anal abscess were identified. Of these, 43 chronic dialysis patients with first-time anal abscess were enrolled. Patients were divided into a surgical group and a nonsurgical group according to the treatment received during hospitalization. The baseline characteristics, clinical findings, treatments and outcomes were obtained and analyzed. The endpoints of this study were in-hospital mortality, one-year mortality and one-year recurrence. RESULTS: Of the 43 patients, 27 (62.7%) received surgical treatment, and 16 (37.2%) received antibiotic treatment alone. There was no significant difference in age, sex, body mass index, smoking habits, comorbidities, or dialysis characteristics between the two groups. Perianal abscess was the most common type of anal abscess, and 39.5% of patients experienced fistula formation. Most patients had mixed aerobic and anaerobic flora. Our data demonstrate that there was no significant difference in hospital stay, one-year survival or recurrence rate between the surgical group and nonsurgical group. However, there was a trend toward better in-hospital survival in patients who received surgical treatment (p=0.082). CONCLUSION: In chronic dialysis patients with anal abscess, there was no statistically significant difference in clinical presentation and outcomes between the surgical and nonsurgical groups, although the surgical group had a trend of better in-hospital survival.

Epidemiology and outcomes of anal abscess in patients on chronic dialysis: a 14-year retrospective study

OBJECTIVES: We conducted this retrospective study to elucidate the clinical presentation and outcomes of anal abscess in chronic dialysis patients. METHODS: We performed a chart review of patients who were hospitalized for anal abscess from Jan. 2002 to Dec. 2015. A total of 3,074 episodes of anal abscess were identified. Of these, 43 chronic dialysis patients with first-time anal abscess were enrolled. Patients were divided into a surgical group and a nonsurgical group according to the treatment received during hospitalization. The baseline characteristics, clinical findings, treatments and outcomes were obtained and analyzed. The endpoints of this study were in-hospital mortality, one-year mortality and one-year recurrence. RESULTS: Of the 43 patients, 27 (62.7%) received surgical treatment, and 16 (37.2%) received antibiotic treatment alone. There was no significant difference in age, sex, body mass index, smoking habits, comorbidities, or dialysis characteristics between the two groups. Perianal abscess was the most common type of anal abscess, and 39.5% of patients experienced fistula formation. Most patients had mixed aerobic and anaerobic flora. Our data demonstrate that there was no significant difference in hospital stay, one-year survival or recurrence rate between the surgical group and nonsurgical group. However, there was a trend toward better in-hospital survival in patients who received surgical treatment (p=0.082). CONCLUSION: In chronic dialysis patients with anal abscess, there was no statistically significant difference in clinical presentation and outcomes between the surgical and nonsurgical groups, although the surgical group had a trend of better in-hospital survival.

The rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model

Dendritic cells (DCs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. The aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (LALNs) in the model of a non-human primate (NHP) infected by influenza A virus (IAV). Cynomolgus macaques were infected with influenza A virus (H3N2) via bronchoscopy. Flow cytometry was used to analyze the DC numbers, maturation status and subsets during the time of acute infection (days 1, 2, 3, 4, 7) and the resolution phase (day 30). A dramatic increase in the numbers of influenza A virus-infected CD11c+CD14- myeloid dendritic cells (mDCs) and CD11c-CD123+ plasmacytoid dendritic cells (pDCs) were observed from day 1 to day 4 and peak up from day 7 post-infection. In lung and lung-associated lymph nodes, the numbers and maturation status of myeloid dendritic cells and plasmacytoid dendritic cells increased more slowly than those in the lung tissues. On day 30 post-infection, influenza A virus challenge increased the number of myeloid dendritic cells, but not plasmacytoid dendritic cells, compared with baseline. These findings indicate that dendritic cells are susceptible to influenza A virus infection, with the likely purpose of increasing mature myeloid dendritic cells numbers in the lung and lung and lung-associated lymph nodes, which provides important new insights into the regulation of dendritic cells in a non-human primate model.

The rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model.

Dendritic cells (DCs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. The aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (LALNs) in the model of a non-human primate (NHP) infected by influenza A virus (IAV). Cynomolgus macaques were infected with influenza A virus (H3N2) via bronchoscopy. Flow cytometry was used to analyze the DC numbers, maturation status and subsets during the time of acute infection (days 1, 2, 3, 4, 7) and the resolution phase (day 30). A dramatic increase in the numbers of influenza A virus-infected CD11c+CD14- myeloid dendritic cells (mDCs) and CD11c-CD123+ plasmacytoid dendritic cells (pDCs) were observed from day 1 to day 4 and peak up from day 7 post-infection. In lung and lung-associated lymph nodes, the numbers and maturation status of myeloid dendritic cells and plasmacytoid dendritic cells increased more slowly than those in the lung tissues. On day 30 post-infection, influenza A virus challenge increased the number of myeloid dendritic cells, but not plasmacytoid dendritic cells, compared with baseline. These findings indicate that dendritic cells are susceptible to influenza A virus infection, with the likely purpose of increasing mature myeloid dendritic cells numbers in the lung and lung and lung-associated lymph nodes, which provides important new insights into the regulation of dendritic cells in a non-human primate model.

The timing and the mode of evolution of wild grapes (Vitis).

Wild grapes are woody climbers, found mostly in temperate regions of the northern hemisphere, comprising the genus Vitis. Despite its importance, the evolutionary history of Vitis is still contentious. Past studies have led to conflicting hypotheses about the phylogeny, speciation events, and biogeographic history of the genus. Here we investigate the evolutionary history of Vitis using data from four chloroplast spacers (trnH-psbA, trnK-rps16, trnF-nahJ, and rpl32-trnL) and the nuclear gene RPB2-I, and we explore mechanisms that could have shaped the observed distribution of current species. Maximum likelihood and Bayesian analyses provided similar results, strongly supporting the presence of two subgenera and suggesting a species clustering within subgenus Vitis that mainly mirrors the disjunction between the Old and New World. Vitis vinifera subsp. sylvestris was found to be sister to the Asian species while three major clades were found in the American species. A network approach confirmed the main geographic groups and highlighted different chloroplast haplotype patterns between Asian and American species. Molecular dating analysis provided the time boundaries to discuss our results. Our study shows wild grape diversification to be a continuous and complex process that concerned the Tertiary as well as the Quaternary, most likely involving both geographical and climatic forces. Local variations in extent and timing of these forces were discussed based on observed differences between groups. In the context of the Tertiary-Quaternary debate, we provide evidence in favor of the "continuous hypothesis" to explain present diversity. Finally, two directions for future research are highlighted: (i) was the earliest grape American or Asian? and (ii) are all modern grape species real?

Selective isolation of multiply charged peptides: a confident strategy for protein identification using a linear trap quadrupole mass spectrometer.

In this work, a method devised for the selective isolation of multiply-charged peptide applied to a complex protein mixture was evaluated for the first time using a mass spectrometer with low resolution (LTQ). In this procedure, all primary amino groups of tryptic peptides derived from human Liver tissue interstitial fluid (TIF) are blocked, restricting their positive charge, at acidic pH, to the presence of histidine and arginine residues. After strong cation exchange chromatography, multiply-charged peptides (#R+#H > 1) are retained in the column and separated with high selectivity from singly (#R+#H = 1) and neutral peptides (#R +#H = 0) which are collected together in the flow-through. Using Liquid chromatography electrospray ionization tandem mass spectrometry analysis the retained fraction displayed a 95% enrichment of multiply charged peptides while in the flow-through; only 4% of multiply-charged peptides were identified.

Phylogenetic relationships between Bacillus species and related genera inferred from 16s rDNA sequences

Neigh-borjoining, maximum-parsimony, minimum-evolution, maximum-likelihood and Bayesian trees constructed based on 16S rDNA sequences of 181 type strains of Bacillus species and related taxa manifested nine phylogenetic groups. The phylogenetic analysis showed that Bacillus was not a monophyletic group. B. subtilis was in Group 1. Group 4, 6 and 8 respectively consisted of thermophiles, halophilic or halotolerant bacilli and alkaliphilic bacilli. Group 2, 4 and 8 consisting of Bacillus species and related genera demonstrated that the current taxonomic system did not agree well with the 16S rDNA evolutionary trees. The position of Caryophanaceae and Planococcaceae in Group 2 suggested that they might be transferred into Bacillaceae, and the heterogeneity of Group 2 implied that some Bacillus species in it might belong to several new genera. Group 9 was mainly comprised of the genera (excluding Bacillus) of Bacillaceae, so some Bacillus species in Group 9: B. salarius, B. qingdaonensis and B. thermcloacae might not belong to Bacillus. Four Bacillus species, B. schlegelii, B. tusciae, B. edaphicus and B. mucilaginosus were clearly placed outside the nine groups.

Árvores utilizando os métodos de neighbor-joining, máxima parcimônia, evolução mínima, máxima verossimilhança e bayesiana, construídas baseadas em seqüências de rDNA 16S de 181 linhagens-tipo de espécies de Bacillus e taxa relacionados, mostraram a formação de nove grupos filogenéticos. A análise filogenética mostrou que Bacillus não é um grupo monofilético. B. subtilis se colocou no Grupo 1. Grupos 4, 6 e 8, respectivamente, consistiram de bacilos termofílicos, halofílicos ou halotolerantes e alcalifílicos. Grupos 2, 4 e 8 consistindo de espécies de Bacillus e gêneros relacionados demonstraram que o sistema taxonômico corrente não concorda perfeitamente com as árvores evolucionárias por rDNA 16S. A posição de Caryophanaceae e Planococcaceae no Grupo 2 sugere que estes podem ser transferidos para Bacillaceae, e a heterogeneidade do Grupo 2 implica em que algumas espécies de Bacillus neste grupo podem pertencer a vários novos gêneros. O Grupo 9 foi principalmente composto de gêneros de Bacillaceae (excluindo Bacillus), portanto algumas espécies de Bacillus no Grupo 9: B. salarius, B. qingdaonensis e B. thermcloacae podem não pertencer a Bacillus. Quatro espécies de Bacillus, B. schlegelii, B. tusciae, B. edaphicus e B. mucilaginosus foram claramente colocadas fora dos nove grupos.

Phylogenetic relationships between Bacillus species and related genera inferred from 16s rDNA sequences

Neigh-borjoining, maximum-parsimony, minimum-evolution, maximum-likelihood and Bayesian trees constructed based on 16S rDNA sequences of 181 type strains of Bacillus species and related taxa manifested nine phylogenetic groups. The phylogenetic analysis showed that Bacillus was not a monophyletic group. B. subtilis was in Group 1. Group 4, 6 and 8 respectively consisted of thermophiles, halophilic or halotolerant bacilli and alkaliphilic bacilli. Group 2, 4 and 8 consisting of Bacillus species and related genera demonstrated that the current taxonomic system did not agree well with the 16S rDNA evolutionary trees. The position of Caryophanaceae and Planococcaceae in Group 2 suggested that they might be transferred into Bacillaceae, and the heterogeneity of Group 2 implied that some Bacillus species in it might belong to several new genera. Group 9 was mainly comprised of the genera (excluding Bacillus) of Bacillaceae, so some Bacillus species in Group 9: B. salarius, B. qingdaonensis and B. thermcloacae might not belong to Bacillus. Four Bacillus species, B. schlegelii, B. tusciae, B. edaphicus and B. mucilaginosus were clearly placed outside the nine groups.

Árvores utilizando os métodos de neighbor-joining, máxima parcimônia, evolução mínima, máxima verossimilhança e bayesiana, construídas baseadas em seqüências de rDNA 16S de 181 linhagens-tipo de espécies de Bacillus e taxa relacionados, mostraram a formação de nove grupos filogenéticos. A análise filogenética mostrou que Bacillus não é um grupo monofilético. B. subtilis se colocou no Grupo 1. Grupos 4, 6 e 8, respectivamente, consistiram de bacilos termofílicos, halofílicos ou halotolerantes e alcalifílicos. Grupos 2, 4 e 8 consistindo de espécies de Bacillus e gêneros relacionados demonstraram que o sistema taxonômico corrente não concorda perfeitamente com as árvores evolucionárias por rDNA 16S. A posição de Caryophanaceae e Planococcaceae no Grupo 2 sugere que estes podem ser transferidos para Bacillaceae, e a heterogeneidade do Grupo 2 implica em que algumas espécies de Bacillus neste grupo podem pertencer a vários novos gêneros. O Grupo 9 foi principalmente composto de gêneros de Bacillaceae (excluindo Bacillus), portanto algumas espécies de Bacillus no Grupo 9: B. salarius, B. qingdaonensis e B. thermcloacae podem não pertencer a Bacillus. Quatro espécies de Bacillus, B. schlegelii, B. tusciae, B. edaphicus e B. mucilaginosus foram claramente colocadas fora dos nove grupos.

Eficácia e tolerabilidade de celecoxibe versus diclofenaco: resultados de um estudo multicêntrico, randomizado, duplo-cego, de não inferioridade, em indivíduos com lombalgia aguda / Efficacy and tolerability of celecoxib versus diclofenac: results of a multicenter, randomized, double-blind, noninferiority study in subjects with acute low back pain

Objetivo: Comparar a eficácia de celecoxibe 200 mg duas vezes ao dia com diclofenaco 75 mg duas vezes ao dia no tratamento de lombalgia aguda (ALBP).Desenho da pesquisa e métodos: Estudo de não inferioridade multicêntrico, randomizado, duplo-cego. Pacientes com lombalgia aguda, Quebec Task Force classe 1 ou 2, com um escore na escala analógica visual (VAS) maior que 50 mm (escala de 100 mm), e dor moderada a grave em uma escala categórica foram randomizados para receber celecoxibe 400 mg mais 200 mg no dia 1, seguido por 200 mg duas vezes ao dia daí em diante (N =123) ou diclofenaco 75 mg duas vezes ao dia (N =121) durante 7 dias. Principais medidas de resultado: O resultado (end point) primário foi a alteração na intensidade da dor (PI) (VAS, mm) do período basal ao dia 3 para a população por protocolo. Os end points secundários incluíram dor e resultados de funcionalidade, além de avaliações de segurança e tolerabilidade. Resultados: As reduções médias pelo método dos mínimos quadrados em intensidade da dor (PI) do período basal ao dia 3 foram semelhantes para celecoxibe (-40,00) e diclofenaco (-42,55). Celecoxibe foi comparável ao diclofenaco, já que o limite inferior do intervalo de confiança de 95% (IC) da diferença estimada (diclofenaco - celecoxibe [-2,56 mm IC 95%: -7,67 a 2,56 mm]) ficou dentro da margem de não inferioridade pré-especificada de - 10 mm. No geral, as taxas de evento adverso foram ligeiramente mais altas no grupo diclofenaco (21,5%) do que no grupo celecoxibe (16,3%). Nove eventos adversos gastrointestinais superiores de intensidade moderada a grave foram relatados em pacientes que utilizaram celecoxibe (7,3%) e 15 em pacientes que utilizaram diclofenaco (12,4%). Conclusão: Celecoxibe 400 mg mais 200 mg no dia 1, seguido por 200 mg duas vezes ao dia daí em diante, proporciona alívio eficaz para dor lombar aguda e foi pelo menos tão eficaz quanto diclofenaco 75 mg duas vezes ao dia, com incidência mais baixa de eventos adversos...