Potential of Negative-Ion-Mode Proteomics: An MS1-Only Approach.

Current proteomics approaches rely almost exclusively on using the positive ionization mode, resulting in inefficient ionization of many acidic peptides. This study investigates protein identification efficiency in the negative ionization mode using the DirectMS1 method. DirectMS1 is an ultrafast data acquisition method based on accurate peptide mass measurements and predicted retention times. Our method achieves the highest rate of protein identification in the negative ion mode to date, identifying over 1000 proteins in a human cell line at a 1% false discovery rate. This is accomplished using a single-shot 10 min separation gradient, comparable to lengthy MS/MS-based analyses. Optimizing separation and experimental conditions was achieved by utilizing mobile buffers containing 2.5 mM imidazole and 3% isopropanol. The study emphasized the complementary nature of data obtained in positive and negative ion modes. Combining the results from all replicates in both polarities increased the number of identified proteins to 1774. Additionally, we analyzed the method's efficiency using different proteases for protein digestion. Among the four studied proteases (LysC, GluC, AspN, and trypsin), trypsin and LysC demonstrated the highest protein identification yield. This suggests that digestion procedures utilized in positive-mode proteomics can be effectively applied in the negative ion mode. Data are deposited to ProteomeXchange: PXD040583.

A New Nasal Restriction Device Called FeelBreathe® Improves Breathing Patterns in Chronic Obstructive Pulmonary Disease Patients during Exercise.

A device called FeelBreathe (FB)® was designed, developed, and patented for inspiratory muscle training. The main aim was to determine the acute responses on lung ventilation, gas exchange, and heart rate during exercise in patients with chronic obstructive pulmonary disease (COPD) with and without the use of FB. In this study, a randomized cross-over trial was performed with 18 men diagnosed with COPD (FEV1 between 30% and 70% of its predicted value). Each participant randomly conducted two trials with 30 min of rest between them with the same protocol on a treadmill for 10 min at a constant rate of 50% of VO2peak. Each test was performed randomly and in a crossover randomized design in two different conditions: (1) oronasal breathing; and (2) nasal breathing with FB (nasal ventilatory flow restriction device). It was observed that FB had positive effects on dynamic hyperinflation, breathing pattern, and breathing efficiency, with higher expiratory and inspiratory time. Despite these differences, blood oxygen saturation percentage, oxygen uptake, and heart rate showed a similar response for both conditions during exercise. The results suggest that exercise performed with FB improved ventilatory responses compared to the oronasal mode in COPD patients. This new tool could be used during most daily tasks and exercise programs.

Unusual records of deepwater teleosteans trawled off the western coast of Mexico.

The first records of three midwater species for the Mexican ichthyofauna (Holtbyrnia laticauda, Brama dussumieri and Cubiceps baxteri), caught off the coast of Baja California, Mexico, in mid 2014, are reported. As far as is known, they are the first verified specimens, geo-referenced and catalogued in a reference fish collection for the west coast of Mexico. The species' known distributions were extended northward in the eastern Pacific Ocean, ranging from 3495 to 8300 km.

Assignment of tumor subtype by genomic testing and pathologic-based approximations: implications on patient's management and therapy selection

BACKGROUND: Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored. METHODS: Ninety-four patients were randomized to neoadjuvant single agent doxorubicin or docetaxel. Tumor subtype was assessed by pathology-based classification and by gene expression using the PAM50 plus the claudin-low predictor (CLP). Kappa Cohen's coefficient (κ) was used to test the agreement between methods. Multivariate Cox proportional hazards analyses were used to determine the significance of each methodology in the prediction of prognosis. Likelihood ratio statistics of both classifications were evaluated. RESULTS: The agreement between pathology-based classification and PAM50 was moderate [κ = 0.551, 95 % confidence interval (95 % CI) 0.467-0.641]. Tumor subtype assessed by both classifications were prognostic for overall survival (OS) and relapse-free survival (P < 0.05). However, PAM50 + CLP provided more prognostic information, in terms of OS, than the pathology-based classification (P < 0.05). Patients with triple negative tumors as well as basal-like tumors had worse OS when first treated with doxorubicin (HR = 5.98, 95 % CI 1.25-28.67, and HR = 5.02, 95 % CI 0.96-26.38, respectively). However, claudin-low tumors did not show significant differences in OS according to neoadjuvant treatment branch. Indeed, we found that claudin-low tumors treated with pre-operative doxorubicin had significantly better OS than basal-like tumors treated with neoadjuvant doxorubicin (adjusted HR = 0.16, 95 % CI 0.04-0.69, P = 0.014). CONCLUSIONS: The assignment of tumor subtype can differ depending on the methodology, which might have implications on patient's management and therapy selection (AU)

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Assignment of tumor subtype by genomic testing and pathologic-based approximations: implications on patient's management and therapy selection.

BACKGROUND: Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored. METHODS: Ninety-four patients were randomized to neoadjuvant single agent doxorubicin or docetaxel. Tumor subtype was assessed by pathology-based classification and by gene expression using the PAM50 plus the claudin-low predictor (CLP). Kappa Cohen's coefficient (κ) was used to test the agreement between methods. Multivariate Cox proportional hazards analyses were used to determine the significance of each methodology in the prediction of prognosis. Likelihood ratio statistics of both classifications were evaluated. RESULTS: The agreement between pathology-based classification and PAM50 was moderate [κ = 0.551, 95 % confidence interval (95 % CI) 0.467-0.641]. Tumor subtype assessed by both classifications were prognostic for overall survival (OS) and relapse-free survival (P < 0.05). However, PAM50 + CLP provided more prognostic information, in terms of OS, than the pathology-based classification (P < 0.05). Patients with triple negative tumors as well as basal-like tumors had worse OS when first treated with doxorubicin (HR = 5.98, 95 % CI 1.25-28.67, and HR = 5.02, 95 % CI 0.96-26.38, respectively). However, claudin-low tumors did not show significant differences in OS according to neoadjuvant treatment branch. Indeed, we found that claudin-low tumors treated with pre-operative doxorubicin had significantly better OS than basal-like tumors treated with neoadjuvant doxorubicin (adjusted HR = 0.16, 95 % CI 0.04-0.69, P = 0.014). CONCLUSIONS: The assignment of tumor subtype can differ depending on the methodology, which might have implications on patient's management and therapy selection.

Estudio del aclaramiento bacteriano en el trasplante esplénico cervical en ratas / Bacterial clearance in rats after cervical spleen transplantation

Introducción. El objetivo de nuestro trabajo es estudiar el aclaramiento bacteriano en el trasplante esplénico cervical en ratas según nuestro modelo experimental. Material y método. Distribución aleatoria de 100 ratas isogénicas tipo Lewis en 4 grupos: grupo control con laparotomía y preservación del bazo, grupo de esplenectomía, grupo de autotrasplante esplénico y grupo de trasplante esplénico heterotópico vascularizado en la región cervical. Se realizó un estudio del aclaramiento bacteriano mediante la determinación del número de colonias/ml de sangre tras infección por neumococos en una dosis de 1 × 107.Resultados. El grupo de trasplante esplénico presenta un efecto protector frente a la bacteriemia superior al de autotrasplante y esplenectomía; aunque inferior al de control. Estas diferencias son estadísticamente significativas (p < 0,05).Conclusiones. Nuestro modelo experimental de trasplante esplénico cervical en ratas consigue, en el aclaramiento bacteriano, valores próximos a la normalidad y superiores a los del autotrasplante esplénico (AU)

Immunohistochemical prognostic index for breast cancer in young women.

AIMS: Women under 35 years of age comprise a small proportion of patients with breast cancer, but determining their prognosis can be difficult. This prospective, multivariate study looked at several factors with the aim of obtaining a useful index to evaluate the prognosis of these women. METHODS: In total, 108 patients below 35 years of age affected by invasive ductal carcinoma without distant metastasis were studied. The mean duration of the follow up period was six years. Histopathological (tumour size, histological grade, and lymph node stage) and immunohistochemical (c-erbB-2, p53, oestrogen receptor, and progesterone receptor) factors were measured in all patients, and the Nottingham prognostic index (NPI) was then calculated. An immunohistochemical prognostic index (IHPI) was created using the arithmetic sum of the four individual immunohistochemical factors. RESULTS: In univariate assessment of survival, all the studied factors yielded a significant association with either overall survival or disease free survival, except for c-erbB-2 and p53 with disease free survival. In univariate calculation of risk, all the factors gave significant results; however, in multivariate analysis only tumour size, histological grade, and progesterone receptor were significant. Both NPI and IHPI correlated significantly with prognosis. In multivariate regression analysis, IHPI correlated with tumour size and there was a significant interaction between both variables. CONCLUSION: IHPI is very useful in determining the prognosis of tumours < or = 2 cm and of moderate use for tumours > 2, although it has no use in tumours > 5 cm.

Complicaciones de la enfermedad diverticular del colon. Estudio comparativo de dos poblaciones / Complications of colonic diverticular disease. Comparative study of two series

Objetivo: comparar el modo de presentación y manejo de la enfermedad en dos Servicios de cirugía de poblaciones geográficas distintas. Diseño: estudio observacional, retrospectivo. Pacientes y método: 203 casos de la 2ª Cátedra de Cirugía del Hospital Universitario de Clínicas de Asunción, Paraguay y 150 casos del Hospital Universitario de Lleida, España. Se analizaron: motivo de ingreso, antecedentes, tratamiento y morbi-mortalidad postoperatoria. Resultados: serie paraguaya: edad media hombres 53 (3484) años y 62 (36-92) mujeres. 55 por ciento ingresaron por complicaciones hemorrágicas y 45 por ciento por diverticulitis aguda. El tratamiento médico se inició en 109 casos y quirúrgico en 110, 72 de urgencia y 38 electivas. La morbilidad fue del 31,8 por ciento (40,2 por ciento en urgencia y 16 por ciento programada, (p<0,05) y la mortalidad del 15,5 por ciento, 22,2 por ciento urgentes y 2,6 por ciento programados p<(0,003).Serie de Lleida: edad media hombres 65,5 (38-85) p<0,005 y mujeres 71,4(30-93) p<0,01) años. 86 por ciento ingresaron por diverticulitis aguda, 10,7 por ciento por hemorragia (p<0,001). Presentaron crisis previa el 16 por ciento (p<0,001). El tratamiento fue médico en 111 casos y quirúrgico en 39 (p<0,001); 33 de urgencia y 6 electivas (p<0,04). La morbilidad fue de 41 por ciento y la mortalidad de 5 (12,8 por ciento), todos de urgencia. La técnica operatoria utilizada fue similar: resección con anastomosis primaria en las electivas y mayoría de Hartmann, en las urgencias, con una proporción de anastomosis inmediata del 33 y 21 por ciento. Conclusiones : posiblemente factores dietéticos y de calidad de vida influyen en la aparición de la enfermedad diverticular. Hay que prevenir la cirugía de urgencia. Cada cirujano debe adaptar su estrategia quirúrgica al medio socio-económico-cultural de la población (AU)

Complications of colonic diverticular disease. Comparative study of two series.

OBJECTIVE: To compare the form of presentation and management of the disease in two surgical units covering geographically different populations. DESIGN: Observational retrospective study. PATIENTS AND METHOD: 203 cases from the 2nd Chair of Surgery of the Hospital Universitario de Clínicas de Asunción, Paraguay and 150 cases from the Hospital Universitario de Lleida, Spain. We analyzed the cause of admission, medical history, treatment and post-operative morbidity and mortality. RESULTS: Paraguay series: average age: 53 years (range 34-84) for men and 62 years (range 36-92) for women. Fifty-five per cent were hospitalized because of hemorrhagic complications and 45% because of acute diverticulitis. Medical treatment was provided in 109 cases and surgery in 110, 72 of which were emergencies and 38 elective procedures (p < 0.05). Morbidity was 31.8% (40.2% in emergencies and 16% in elective procedures, p < 0.05) and mortality was 15.5% (20.2% in emergencies and 2.6% in elective procedures, p < 0.003). LLEIDA SERIES: Average age: 65.5 years (range 38-85, p < 0.01) for men and 71.4 years (range 30-93, p < 0.01) for women. Eighty-six per cent were hospitalized because of acute diverticulitis and 10.7% because of acute hemorrhage (p < 0.001). Sixteen per cent have had previous attacks (p < 0.001). Medical treatment was provided to 111 patients and surgery to 39 (p < 0.001), 33 of which were emergencies and 6 elective procedures (p < 0.04). Morbidity was 41% and mortality 12.8% (5 cases), all of which were emergencies. The surgical technique was similar in both groups: resection with primary anastomosis in elective procedures and Hartmann's procedure in most emergencies, with a rate of immediate anastomosis of 33 and 21%, respectively. CONCLUSIONS: Factors related to nutrition and quality of life may influence the development of diverticular disease. Emergency surgery should be prevented. Surgeons must adapt their surgical approach to the socioeconomic and cultural medium of the population.