Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment.

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.

Lactancia materna exclusiva y trabajo. Su importancia en la medicina del trabajo / Exclusive breastfeeding and work. Its importance in occupational health

En todos los ámbitos laborales, sin excepción, es imprescindible la vigencia ineludible del derecho irrestricto de toda madre a ejercer, practicar, su lactancia con su bebé. Y las razones médicas debieran formar parte de campañas incesantes para que este derecho de las mamás esté absolutamente naturalizado en todos los niveles y en cada rincón del país. La lactancia materna protege al bebé de enfermedades infecciosas y le da la nutrición ideal para una vida más sana. Es fundamental desde el primer día de vida extrauterina hasta los 6 meses con exclusividad y luego continúa con suplementos vitamínicos y nutrientes apropiados. En todo lugar de trabajo deben existir lactarios como una estrategia de Salud Pública y en Medicina del Trabajo. (AU)

In all areas of work, without exception, the unavoidable validity of the unrestricted right of every mother to exercise, practice, breastfeeding with her baby is essential. And the medical reasons should be part of incessant campaigns so that this right of mothers is absolutely naturalized at all levels and in every corner of the country. Breastfeeding protects the baby from infectious diseases and gives it the ideal nutrition for a healthier life. It is essential from the first day of extrauterine life until 6 months exclusively and then continues with appropriate vitamin and nutrient supplements. In every workplace there must be lactation rooms as a strategy of Public Health and Occupational Medicine. (AU)

Outcomes and clinical characteristics of the compassionate use of plitidepsin for immunocompromised adult patients with COVID-19.

OBJECTIVES: To evaluate the compassionate use of plitidepsin as an antiviral treatment in hospitalized immunocompromised adult patients with moderate-to-severe COVID-19. DESIGN: Retrospective observational study of data -collected from January 01, 2021 to April 30, 2022- from 35 immunocompromised adult patients with COVID-19 non-eligible for other available antiviral treatments. Main outcome measures were time to respiratory recovery (SpFi ≥ 315); COVID-19-related 30-day-cumulative mortality after first plitidepsin infusion; and time to undetectable levels of viral RNA. RESULTS: Thirty-three patients receiving a full course of plitidepsin (2.5 mg [n = 29] or 1.5 mg [n = 4]) were included. Most (69.7%) had a malignant hematologic disease and 27.3% had solid tumors. A total of 111 infusions were administered with lack of relevant safety events. Median time from plitidepsin initiation to SpFi ≥315 was 8 days (95% confidence interval [CI], 7-19). Median time to first negative reverse transcription-polymerase chain reaction for SARS-CoV-2 (cycle threshold >36) was 17 days (95% CI 13-25). Mortality rate was 16.3% (95% CI 3-37.3). CONCLUSION: These data support plitidepsin as a well-tolerated treatment that might have potential clinical and antiviral efficacy in COVID-19 immunocompromised patients.

Asistencia del recién nacido con hernia diafragmática congénita / Care of newborns with congenital diaphragmatic hernia / Cuidados ao recém-nascido com hérnia diafragmática congênita

La hernia diafragmática congénita es un defecto en el diafragma que lleva a la herniación del contenido abdominal a la cavidad torácica durante el período intrauterino. La morbimortalidad está determinada por la asociación con otras malformaciones, el grado de hipoplasia pulmonar y la presencia de hipertensión pulmonar secundaria. Presenta una incidencia estimada de 1 cada 2.500-3.000 recién nacidos vivos, constituyendo en un 60% una malformación aislada. Es una patología evolutiva que puede ser diagnosticada a partir de la semana 20-24, la ubicación más habitual es la posterolateral izquierda. Se trata de una patología que requiere ingreso a cuidados intensivos al nacimiento y luego de lograda la estabilización del paciente es de sanción quirúrgica. Los objetivos de este trabajo son conocer las características generales de la patología para sistematizar el manejo logrando así un óptimo asesoramiento de los padres a nivel prenatal y seguimiento postnatal del recién nacido.

Congenital diaphragmatic hernia is a defect in the diaphragm that leads to herniation of theabdominal contents of the thoracic cavity during the intrauterine period. Morbidity and mortality are determined by the association with other malformations, the degree ofpulmonary hypoplasia and the presence of secondary pulmonary hypertension.It has an estimated incidence of 1 every 2,500-3,000 live newborns, and in 60% of the cases it is an isolated malformation. It is an evolutionary pathology that can be diagnosed from week 20-24; it is most commonly located in the left posterolateral. It is a pathology that requires intensive care at birth and after delivery and once the patient has been stabilized, surgical action is required. The objectives of this work are to understand the general characteristics of the pathology in order to refine its manipulation and achieve optimal counseling for parents at the newborn's prenatal and postnatal stages.

A hérnia diafragmática congênita é um defeito no diafragma que leva à herniação doconteúdo abdominal para a cavidade torácica durante o período intrauterino. A morbimortalidade é determinada pela associação com outras malformações, pelo grau de hipoplasia pulmonar e pela presença de hipertensão pulmonar secundária. Apresenta uma incidência estimada de 1 a cada 2.500-3.000 nascidos vivos, constituindo-se em 60% uma malformação isolada. É uma patologia evolutiva que pode ser diagnosticada a partir da semana 20-24 e a localização mais comum é o póstero-lateral esquerdo. É uma patologia que requer internação em terapia intensiva ao nascimento e após o parto. Uma vez que o paciente for estabilizado, é necessária ação cirúrgica. Os objetivos deste paper são conhecer as características gerais da patologia para melhorar o seu manejo, obtendo assim um aconselhamento ideal para os pais no nível pré-natal e no acompanhamento do crescimento pós-natal do recém-nascido.

Repercusiones cardíacas en pacientes con pectus excavatum: puesta al día. Segunda parte / Cardiac repercussions in patients with pectus excavatum: update. Part two / Repercussões cardíacas em pacientes com pectus excavatum: atualização. Parte dois

El pectus excavatum (PEX) es una deformación de la pared torácica que obedece a una alteración de los cartílagos costales con el consiguiente hundimiento del esternón. Históricamente, se clasificaba como un defecto únicamente estético o cosmético, sin embargo, en los últimos años se han desarrollado nuevos métodos de estudio para la valoración de las repercusiones de esta patología. Existe cada vez más bibliografía que demuestra importantes repercusiones funcionales. Se realizó una puesta al día de las repercusiones cardíacas de la patología y un análisis de los artículos más relevantes de los últimos años. La evidencia actual permite afirmar que existe una afectación cardíaca por compresión esternal en la mayoría de los pacientes con PEX. Las afectaciones incluyen alteraciones anatomofuncionales (trastornos del ritmo, disminución del llenado ventricular), del volumen sistólico, aumento de la presión de la aurícula derecha, valvulopatías, compresión del ventrículo derecho, derrame pericárdico, entre otras. Todo lo cual permite concluir que el PEX puede presentar importantes alteraciones cardíacas que deben ser tenidas en cuenta a la hora de valorar los pacientes con esta patología.

Pectus excavatum (PEX) is a deformation of the chest wall caused by an alteration of the costal cartilages with the consequent collapse of the sternum. Historically, it had been classified as a solely aesthetic or cosmetic defect, however, in recent years new study methods have been developed to assess the repercussions of this pathology, with increasing bibliography showing important functional consequences. We updated the cardiac pathological repercussions and analyzed the most relevant articles of recent years. The current evidence suggests that there is cardiac involvement due to sternal compression in most patients with PEX. These affectations include anatomical functional alterations: rhythm disorders, decreased ventricular filling, decreased stroke volume, increased right atrial pressure, valve disease, right ventricular compression, pericardial effusion, among others. All of which enables us to conclude that PEX can present important cardiac alterations that must be taken into account when assessing patients with this pathology.

Pectus excavatum (PEX) é uma deformação da parede torácica decorrente de uma alteração das cartilagens costais com consequente colapso do esterno. Historicamente, foi classificado como um defeito exclusivamente estético ou cosmético, porém, nos últimos anos, novos métodos de estudo foram desenvolvidos para avaliar as repercussões dessa patologia, com crescente bibliografia mostrando importantes repercussões funcionais. Foi realizada uma atualização das repercussões cardíacas da patologia e análise dos artigos mais relevantes dos últimos anos. As evidências atuais permitem afirmar que há acometimento cardíaco por compressão esternal na maioria dos pacientes com PEX. As afecções incluem alterações anatomofuncionais: distúrbios do ritmo, diminuição do enchimento ventricular, diminuição do volume sistólico, aumento da pressão atrial direita, doença valvular, compressão do ventrículo direito, derrame pericárdico, entre outras. Tudo isso permite concluir que o PEX pode apresentar alterações cardíacas importantes que devem ser levadas em consideração na avaliação de pacientes com essa patologia.

Repercusiones pulmonares en pacientes con pectus excavatum: puesta al día / Pulmonary consequences on patients with pectus excavatum: update / Repercussões pulmonares em pacientes com pectus excavatum: atualização

El pectus excavatum (PEX) es una deformación de la pared torácica que obedece a una alteración de los cartílagos costales con el consiguiente hundimiento del esternón. Históricamente se clasificaba como un defecto únicamente estético o cosmético, sin embargo en los últimos años se han desarrollado nuevos métodos de estudio para la valoración de las repercusiones de esta patología, y existe cada vez más bibliografía que demuestra importantes repercusiones funcionales. Se realizó una puesta al día de las repercusiones pulmonares de la patología y análisis de los artículos más relevantes de los últimos años. Los síntomas respiratorios son frecuentes, estando presentes en más de la mitad de los pacientes. Se ha demostrado una disminución de la CVF, VEF1 y PEF25%-75%; así como la presencia de un patrón restrictivo y/o obstructivo, un aumento del VR y una alteración de la dinámica respiratoria. Se ha objetivado la afectación del PEX sobre la función pulmonar, determinando categóricamente que esta patología presenta una importante repercusión funcional.

Pectus excavatum (PEX) is a thoracic wall malformation due to an alteration of the costal cartilages with subsequent sinking of the sternum. Historically, it was considered a mere aesthetic or cosmetic defect, however, in recent years, new assessment methods have been developed to evaluate the repercussions of this pathology, and there is an increasing literature that demonstrates important functional consequences. We carried out an update of this pathology's pulmonary repercussions and analyzed the most relevant articles of the recent years. Respiratory symptoms are frequent, present in more than half of the patients. A decrease in FVC, FEV1 and PEF25%-75% has been shown; as well as the presence of a restrictive and/or obstructive pattern, an increase in RV and an alteration in respiratory dynamics. The affectation of PEX on pulmonary function has been objectified, and it has been determined categorically that this pathology has important functional consequences.

Pectus excavatum (PEX) é uma deformação da parede torácica devido a uma alteração das cartilagens costais com consequente afundamento do esterno. Historicamente, foi classificado como um defeito exclusivamente estético ou cosmético, porém, nos últimos anos, novos métodos de estudo foram desenvolvidos para avaliar as repercussões dessa patologia, e há uma literatura crescente que demonstra importantes repercussões funcionais. Foi realizada uma atualização das repercussões pulmonares da patologia e análise dos artigos mais relevantes dos últimos anos. Os sintomas respiratórios são frequentes, estando presentes em mais da metade dos pacientes. Foi demonstrada uma diminuição da CVF, VEF1 e PEF25-75%; bem como a presença de padrão restritivo e/ou obstrutivo, aumento do VD e alteração da dinâmica respiratória. A afetação do PEX na função pulmonar tem sido objetivada, determinando categoricamente que esta patologia apresenta importante repercussão funcional.

Flipped Inflammatory Time and the Role of Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2: Optimizing Tocilizumab Against Coronavirus Disease 2019.

Use of interleukin (IL-6) inhibitors has become one of the most complicated clinical issues in treating coronavirus disease 2019 (COVID-19). Recently, randomized open-label platform trials have found that IL-6 inhibitors have a beneficial effect on mortality in severe COVID-19. However, several questions arise around their mechanism of action in this disease, as well as how, when, and at which dose they should be used. IL-6 has both proinflammatory and anti-inflammatory effects, which may modulate the course of COVID-19, whose immunopathogenesis is driven by the innate immune system, autoantibodies, and interferon. Given that patients with delayed seroconversion against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein would be at the highest risk of complications beyond the second week of disease, we propose that considering patient serostatus at admission could optimize the use of IL-6 inhibitors in COVID-19. We predict that the net treatment benefits could be higher in the subgroup of patients with delayed seroconversion as compared to those who seroconvert more rapidly after SARS-CoV-2 infection.

Disruption of hepatic one-carbon metabolism impairs mitochondrial function and enhances macrophage activity in methionine-choline-deficient mice.

One-carbon metabolism is a collection of metabolic cycles that supports methylation and provides one-carbon bound folates for the de novo synthesis of purine and thymidine nucleotides. The methylation of phosphatidylethanolamine to form choline has been extensively studied in the context of fatty liver disease. However, the role of one-carbon metabolism in supporting nucleotide synthesis during liver damage has not been addressed. The objective of this study is to determine how the disruption of one-carbon metabolism influences nucleotide metabolism in the liver after dietary methionine and choline restriction. Mice (n=8) were fed a methionine-choline-deficient or control diet for 3 weeks. We treated mice with the compound alloxazine (0.5 mg/kg), a known adenosine receptor antagonist, every second day during the final week of feeding to probe the function of adenosine signaling during liver damage. We found that concentrations of several hepatic nucleotides were significantly lower in methionine- and choline-deficient mice vs. controls (adenine: 13.9±0.7 vs. 10.1±0.6, guanine: 1.8±0.1 vs. 1.4±0.1, thymidine: 0.0122±0.0027 vs. 0.0059±0.0027 nmol/mg dry tissue). Treatment of alloxazine caused a specific decrease in thymidine nucleotides, decrease in mitochondrial content in the liver and exacerbation of steatohepatitis as shown by the increased hepatic lipid content and altered macrophage morphology. This study demonstrates a role for one-carbon metabolism in supporting de novo nucleotide synthesis and mitochondrial function during liver damage.

Reanimación cardiopulmonar (RCP) en el lugar de trabajo. normativas de capacitación en medicina del trabajo / Cardiopulmonary resuscitation inthe workplaceTraining regulations in occupational medicine

Tanto en personas adultas como en jóvenes y niños, aprender primeros auxilios y reanimación cardiopulmonar (RCP) hace la diferencia entre la vida y la muerte en toda actividad humana. Se debe capacitar a cada trabajador en su lugar de labor. Puede suceder en escuelas, universidades, en la práctica deportiva, en la actividad aeroportuaria, en una aeronave, en la actividad de la seguridad privada, gimnasios, centros comerciales, oficinas, como en los templos, radios, estudios televisivos, recitales, aeropuertos, hoteles y en todo otro lugar donde se encuentren muchas personas circulando. También es muy útil saber qué hacer ante un problema de salud en el hogar. Se expone cómo realizar la capacitación en RCP y Primeros Auxilios en el trabajo.

Both in adults, as in young people and children, learning first aid and cardiopulmonary resuscitation (RCP) makes the difference between life and death in all human activity. Each worker must be trained in their workplace. It can happen in schools, universities, in sports practice, in the airport activity, in an aircraft, in the activity of private security, gyms, shopping centers, offices, as in temples, radios, television studios, recitals, airports, hotels and everywhere else where there are many people circulating. It is also very useful to know what to do when faced with a health problem at home. It is exposed how to perform CPR and First Aid training at work.

Síndrome de POEMS, el desafío diagnóstico de un caso infrecuente / POEMS syndrome, the diagnostic challenge of an infrequent case / Síndrome de POEMS, o desafio diagnóstico de um caso infrequente

Se reporta el caso de un hombre de 45 años con síntomas y signos consistentes con el Sindrome de POEMS (del inglés: polineuropatía, organomegalia, endocrinopatía, gammapatía monoclonal y cambios dérmicos), un raro desorden paraneoplásico. El mismo contaba con antecedentes de tabaquismo, hipotiroidismo y últimamente había perdido 20 kg de peso. Se destaca que una historia clínica y revisión detallada seguida de estudios de laboratorio, radiología y biopsia de médula ósea, entre otros, son herramientas necesarias para reconocer los componentes de este síndrome y no demorar el diagnóstico. El paciente presentó 2 criterios obligatorios (gammapatía monoclonal y neuropatia periférica sensitivo-motora), un criterio mayor (lesión ósea) y varios criterios menores (desórdenes endocrinos, manifestaciones cutáneas, organomegalia). Actualmente se encuentra bajo supervisión hematológica y continúa su seguimiento neurológico, lo que muestra una buena respuesta a la terapia específica. Las enfermedades raras como este síndrome resultan un desafío diagnóstico para los profesionales de la salud.

The case of a 45 - year- old- man whose symptoms and signs were consistent with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes), a rare paraneoplastic disorder, has been reported. He had a previous history of smoking, hypothyroidism and a 20 kg weight loss. It was emphasized that a detailed clinical history and examination followed by laboratory and radiological studies and bone marrow biopsy, among others tests, were necessary in order to recognise the components of this syndrome and not to delay the time of diagnosis. This patient had two mandatory criteria (monoclonal gammopathy and sensorimotor polyneuropathy), one major criterion (bone lesion) and several minor criteria (endocrine disorders, cutaneous manifestations, organomegaly). He is currently under the supervision of the doctors of the hematology department and continues neurological follow-up, having a good response to the specific therapy. Rare diseases like this syndrome are a diagnostic challenge for health professionals.

Informa-se o caso de um homem de 45 anos com sintomas e sinais compatíveis com a Síndrome de POEMS (do inglês: polineuropatia, organomegalia, endocrinopatia, gamopatia monoclonal e alterações cutâneas), um distúrbio paraneoplásico raro. O homem tinha antecedentes de tabagismo, hipotiroidismo e ultimamente tinha perdido 20 kg de peso. Enfatizamos que um prontuario médico e exame detalhado, seguido de estudos de laboratório e radiológicos, e uma biópsia de medula óssea, dentre outros, são ferramentas necessárias para reconhecer os componentes desta síndrome e não demorar o tempo de diagnóstico. Nosso paciente apresentou dois critérios obrigatórios (gamopatia monoclonal e neuropatia periférica sensório-motora), um critério maior (lesão óssea) e vários critérios menores (anormalidades endócrinas, alterações cutâneas, organomegalia). Encontra-se atualmente sob supervisão hematológica e continua seu seguimento neurológico, mostrando uma resposta boa à tera,pia concreta. Doenças raras como essa síndrome são um desafio diagnóstico para os profissionais da saúde.

La ergonomía de la persona. la medicina del trabajo en la aviación y en el trabajo médico / Work medicine and the ergonomics of the person

La Organización Internacional de Trabajo (OIT) señala que la magnitud de las lesiones, enfermedades y muertes ocasionadas por el trabajo indica la necesidad imperiosa de los Estados de proseguir la acción para reducirlas. Medicina del trabajo y ergonomía de la persona. Importancia de los exámenes médicos en la prevención de accidentes y enfermedades laborales.

The International Labour Organization (ILO) indicates that the magnitude of work-related injuries, illnesses and deaths caused by work, indicates the imperative need for States to continue to reduce them. Medicine the work and ergonomics of the person, importance of medical examinations in prevention of accidents and labor diseases.

Study on adherence to treatment with imatinib in chronic myeloid leukaemia and its association with therapeutic response.

OBJECTIVE: To assess the level of adherence to treatment with imatinib in patients with chronic myeloid leukaemia and its association with therapeutic response. MATERIALS AND METHODS: Study conducted on October, 2013 - March, 2014, including patients diagnosed with Chronic Myeloid Leukaemia on treatment with imatinib in the hospital. Therapeutic adherence was assessed through the standard Morisky-Green Questionnaire and the medication dispensing record. Those patients who did not complete 6 months of treatment and/or did not complete the questionnaire were excluded. Therapeutic response was assessed following clinical guidelines. The descriptive analysis of variables and correlation was conducted through Pearsons's Chi-Square Test. RESULTS: The study included 31 patients. When assessing the level of association between response variables and therapeutic adherence: 1. The highest molecular response was reached by 68.4% of those patients with high adherence, and by 75% of those patients with intermediate adherence. 2. Complete molecular response was achieved by 57.9% of patients with high adherence, and by 58.3% of patients with intermediate adherence. No statistically significant differences were found in response variables between patients with high and intermediate therapeutic adherence. No association was observed between level of adherence and therapeutic response. CONCLUSIONS: We cannot confirm that a different level of therapeutic adherence might have an impact on response to imatinib, though this should be taken into account in cases of therapeutic failure or sub-optimal response.

Objetivo: El objetivo es evaluar el grado de adhesión terapéutica a imatinib en pacientes con leucemia mieloide crónica y su relación con la respuesta terapéutica. Material y métodos: Estudio realizado en octubre 2013-marzo 2014 que incluye a pacientes diagnosticados de leucemia mieloide crónica en tratamiento con imatinib en el hospital. Se evaluó la adhesión terapéutica mediante el cuestionario estandarizado Morisky-Green y el registro de dispensaciones de medicación. Se excluyeron aquellos que no completaron 6 meses de tratamiento y/o no realizaron el cuestionario. La respuesta terapéutica se evaluó siguiendo guías clínicas. Se realizó el análisis descriptivo de variables y correlación mediante test Chi-cuadrado de Pearson. Resultados: Se incluyeron 31 pacientes. Al evaluar el grado de asociación entre variables de respuesta y adhesión terapéutica: 1. La respuesta molecular mayor fue alcanzada por el 68,4% de los pacientes con alta adhesión y por el 75% de los pacientes con adhesión media. 2. La respuesta molecular completa fue alcanzada por el 57,9% de los pacientes con alta adhesión y por el 58,3% de los pacientes con adhesión media. No se observaron diferencias estadísticamente significativas en las variables de respuesta entre pacientes con adhesión terapéutica alta y media. No se observó asociación entre el grado de adhesión y la respuesta terapéutica. Conclusiones: No podemos afirmar que el distinto grado de adhesión terapéutica influya en la respuesta al imatinib, aunque debería considerarse en casos de fallo terapéutico o respuesta subóptima.

Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice(1,2,3).

Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promotes corticostriatal activity and locomotor sensitization through upstream changes in the activity of tonically active cholinergic interneurons (ChIs). We used a model of operant drug-taking behaviors, in which mice self-administered amphetamine through an in-dwelling catheter. Mice acquired amphetamine self-administration under fixed and increasing schedules of reinforcement. Following a period of abstinence, we determined whether nicotinic acetylcholine receptors modified drug-seeking behavior and associated alterations in ChI firing and corticostriatal activity. Mice responding to conditioned reinforcement showed reduced ChI and corticostriatal activity ex vivo, which paradoxically increased following an amphetamine challenge. Nicotine, in a concentration that increases Ca(2+) influx and desensitizes α4ß2*-type nicotinic receptors, reduced amphetamine-seeking behaviors following abstinence and amphetamine-induced locomotor sensitization. Nicotine blocked the depression of ChI firing and corticostriatal activity and the potentiating response to an amphetamine challenge. Together, these results demonstrate that nicotine reduces reward-associated behaviors following repeated amphetamine and modifies the changes in ChIs firing and corticostriatal activity. By returning glutamatergic activity in amphetamine self-administering mice to a more stable and normalized state, nicotine limits the depression of striatal activity in withdrawal and the increase in activity following abstinence and a subsequent drug challenge.

Antitumor activity of human hydatid cyst fluid in a murine model of colon cancer.

This study evaluates the antitumor immune response induced by human hydatic cyst fluid (HCF) in an animal model of colon carcinoma. We found that anti-HCF antibodies were able to identify cell surface and intracellular antigens in CT26 colon cancer cells. In prophylactic tumor challenge experiments, HCF vaccination was found to be protective against tumor formation for 40% of the mice (P = 0.01). In the therapeutic setting, HCF vaccination induced tumor regression in 40% of vaccinated mice (P = 0.05). This vaccination generated memory immune responses that protected surviving mice from tumor rechallenge, implicating the development of an adaptive immune response in this process. We performed a proteomic analysis of CT26 antigens recognized by anti-HCF antibodies to analyze the immune cross-reactivity between E. granulosus (HCF) and CT26 colon cancer cells. We identified two proteins: mortalin and creatine kinase M-type. Interestingly, CT26 mortalin displays 60% homology with E. granulosus hsp70. In conclusion, our data demonstrate the capacity of HCF vaccination to induce antitumor immunity which protects from tumor growth in an animal model. This new antitumor strategy could open new horizons in the development of highly immunogenic anticancer vaccines.

Evaluation of environmental contamination by platinum and exposure risks for healthcare workers during a heated intraperitoneal perioperative chemotherapy (HIPEC) procedure.

UNLABELLED: The study was plan to assess platinum (Pt) contamination in the operating room and its exposure to health workers during heated intraperitoneal perioperative chemotherapy (HIPEC) using oxaliplatin. MATERIALS AND METHODS: Pt was measured in urinary and environmental (air and surfaces) samples via inductively coupled plasma mass spectrometry (ICP-MS). Urinary samples were obtained from 11 members of the staff before and after the procedure and from 6 controls. Samples from 15 surfaces and from 3 filters from the air extractors were also analyzed for Pt contamination. RESULTS: Before HIPEC, Pt levels in urinary samples were similar in both the exposed and control groups; concentrations were below the limit of detection (i.e., 1.5 ng/L). No elevation was observed in the exposed group at the end of the procedure. Surgeon gloves were heavily contaminated. On other analyzed surfaces, lesser amounts of Pt were measured, ranging from 2 ng on the surgeon's hands to 183 ng on the forceps. All three air filters tested negative. CONCLUSION: No contamination of healthcare workers or of the air in the operating room was detected. However, the heavy contamination of the surgeon's gloves demonstrates why doubling of specialized gloves for the surgeon should be mandatory.

Prospective Coronary CT Angiography 128-MDCT Versus Retrospective 64-MDCT: Improved Image Quality and Reduced Radiation Dose.

OBJECTIVE: new technologies for computed tomography coronary arteries imaging aim to reduce the radiation dose whilst maintaining image quality. The purpose of our study was to compare radiation dose and image quality parameters of Coronary Computed Tomography Angiography (CCTA) performed with retrospective 64-MDCT and prospective 128-MDCT. PATIENTS AND METHODS: a series of 77 consecutive patients were first randomised to either retrospective 64-MDCT (n=37) or prospective 128-MDCT (n=40) for CCTA. All patients in the retrospective 64-MDCT group were scanned with tube current modulation as strategy for reduction dose. Data regarding acquisition time and radiation dose were recorded. Two blinded radiologists independently assessed image quality of all coronary segments by using a four-point scale (1, excellent; 4, poor). Discrepancies were settled by consensus. RESULTS: No significant differences were found regarding sex, age, body weight and heart rate. CTTA effective radiation dose was 2.1 ± 0.9 vs. 8.2 ± 4mSv in prospective and retrospective ECG-gating MDCT groups, respectively. Mean image quality score was 2.2 ± 0.9 for prospective 128-MDCT group and 1.4 ± 0.7 points for retrospective 64-MDCT representing a mean difference of 0.8 points (CI: 0.9 to 0.7). CONCLUSION: in selected patients, CCTA using a 128-MDCT with prospective ECG-gating provides higher image quality with significant lower radiation dose when compared to 64-MDCT using retrospective ECG-gating.

Coronary computed tomography angiography in a single cardiac cycle with a mean radiation dose of approximately 1 mSv: initial experience.

INTRODUCTION: The aim of this study was to evaluate the radiation dose, image quality and acquisition time of coronary computed tomography angiography (CCTA) using a 128-slice dual source scanner with prospective ECG-triggered high-pitch spiral acquisition (Flash Spiral). METHODS: A series of 20 consecutive patients in sinus rhythm, with no contraindications to administration of iodinated contrast media and beta-blockers and no history of coronary revascularization, underwent CCTA either to rule out coronary artery disease (CAD) or to evaluate known or suspected CAD. Image quality was evaluated using a four-point scale (1 excellent, 4 poor). Data on acquisition time and radiation dose were recorded. RESULTS: Mean acquisition time was 292 +/- 21 milliseconds. The mean effective radiation dose was 0.99 mSv +/- 0.34 mSv. All of the 266 coronary artery segments analyzed were of diagnostic image quality. CONCLUSION: CCTA using a 128-slice dual source scanner with prospective ECG-triggered high-pitch spiral acquisition provides single cardiac cycle acquisition with high image quality at mean effective radiation doses of approximately 1 mSv.