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BACKGROUND: The severe acute respiratory syndrome Coronarovirus-2 associated still causes a significant number of deaths and hospitalizations mainly by the development of respiratory failure. We aim to validate lung ultrasound score in order to predict mortality and the severity of the clinical course related to the need of respiratory support. METHODS: In this prospective multicenter hospital-based cohort study, all adult patients with diagnosis of SARS-CoV-2 infection, performed by real-time reverse transcription polymerase chain reaction were included. Upon admission, all patients underwent blood gas analysis and lung ultrasound by expert operators. The acquisition of ultrasound scan was performed on 12 peculiar anatomic landmarks of the chest. Lung ultrasound findings were classified according to a scoring method, ranging 0 to 3: Score 0: normal A-lines. Score 1: multiple separated B-lines. Score 2: coalescent B-lines, alteration of pleural line. Score 3: consolidation area. RESULTS: One thousand and seven patients were included in statistical analysis (male 62.4 %, mean age 66.3). Oxygen support was needed in 811 (80.5 %) patients. The median ultrasound score was 24 and the risk of having more invasive respiratory support increased in relation to higher values score computed. Lung ultrasound score showed negative strong correlation (rho: -0.71) with the P/F ratio and a significant association with in-hospital mortality (OR 1.11, 95 %CI 1.07-1.14; p < 0.001), even after adjustment with the following variables (age, sex, P/F ratio, SpO2, lactate, hypertension, chronic renal failure, diabetes, and obesity). CONCLUSIONS: The novelty of this research corroborates and validates the 12-field lung ultrasound score as tool for predicting mortality and severity clinical course in COVID-19 patients. Baseline lung ultrasound score was associated with in-hospital mortality and requirement of intensive respiratory support and predict the risk of IOT among COVID-19 patients.
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Humanos , Lactante , Preescolar , Niño , Polineuropatías/diagnóstico , Trastornos de la Visión/diagnóstico , Epilepsias Parciales/diagnóstico , Xantogranuloma Juvenil/diagnóstico , Neurofibromatosis/complicaciones , Neurofibromatosis/diagnóstico , Neurofibromatosis/diagnóstico por imagen , Meningioma/diagnóstico , Discapacidad Intelectual/diagnóstico , Neurilemoma/diagnóstico , Diagnóstico DiferencialRESUMEN
INTRODUCTION: Patients presenting breast actinic damage or implant-related complications require an autologous approach to breast reconstruction. However, when they are not good candidates for microsurgical procedures, alternative solutions must be sought. Latissimus dorsi (LD) is a workhorse flap in breast reconstruction, but often the amount of skin and volume achievable are insufficient. Taking inspiration from the Kiss flap concept, the authors hereby describe the "Kiss" LD flap to achieve totally autologous breast reconstruction. PATIENTS AND METHODS: A prospective service evaluation of all patients who underwent breast reconstruction with Kiss LD flap between 2018 and 2020 was performed. Patient demographics and operative variables were recorded, together with early and late complications. Patient satisfaction and quality of life were registered using the latest BREAST-Q reconstruction module, which includes specific LD scales. The questionnaire was administered to patients preoperatively and six months postoperatively. RESULTS: Thirty patients underwent total autologous breast reconstruction with Kiss LD flap. Breast cancer and breast sarcoma resection were followed by reconstruction. The timing of reconstruction was immediate in 3 cases and delayed in 27 cases. No major complications nor total flap loss were registered. BREAST-Q scores postoperatively were significantly higher than the preoperative ones in every domain (p<0.0001) except for the physical well-being of back and shoulder, where the scores differed slightly and non-significantly (p=0.05). CONCLUSIONS: The Kiss LD flap allows to harvest a large amount of skin to restore the breast envelope and a considerable volume to reconstruct the breast mound in a completely autologous procedure.
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Neoplasias de la Mama , Mamoplastia , Músculos Superficiales de la Espalda , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamoplastia/métodos , Complicaciones Posoperatorias/cirugía , Estudios Prospectivos , Calidad de Vida , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: We aimed to assess the correlation between LUS Soldati proposed score and clinical presentation, course of disease and the possible need of ventilation support/intensive care. PATIENTS AND METHODS: All consecutive patients with laboratory confirmed SARS-CoV-2 infection and hospitalized in two COVID Centers were enrolled. All patients performed blood gas analysis and lung ultrasound (LUS) at admission. The LUS acquisition was based on standard sequence of 14 peculiar anatomic landmarks with a score between 0-3 based on impairment of LUS picture. Total score was computed with their sum with a total score ranging 0 to 42, according to Soldati LUS score. We evaluated the course of hospitalization until either discharge or death, the ventilatory support and the transition in intensive care if needed. RESULTS: One hundred and fifty-six patients were included in the final analysis. Most of patients presented moderate-to-severe respiratory failure (FiO2 <20%, PaO2 <60 mmHg) and consequent recommendation to invasive mechanic ventilation (CPAP/NIV/OTI). The median ultrasound thoracic score was 28 (IQR 18-36) and most of patients could be ascertained either in a score 2 (40%) or score 3 pictures (24.4%). The bivariate correlation analysis displayed statistically significant and high positive correlations between the LUS score and the following parameters: ventilation (rho=0.481, p<0.001), lactates (rho=0.464, p<0.001), dyspnea (rho=0.398, p=0.001) mortality (rho=0.410, p=0.001). Conversely, P/F (rho= -0.663, p<0.001), pH (rho = -0.363, p=0.003) and pO2 (rho = -0.400 p=0.001) displayed significant negative correlations. CONCLUSIONS: LUS score improve the workflow and provide an optimal management both in early diagnosis and prognosis of COVID-19 related lung pathology.
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COVID-19/diagnóstico por imagen , COVID-19/epidemiología , Hospitalización/tendencias , Pulmón/diagnóstico por imagen , Anciano , Análisis de los Gases de la Sangre/métodos , Análisis de los Gases de la Sangre/tendencias , COVID-19/terapia , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ultrasonografía/métodos , Ultrasonografía/tendenciasRESUMEN
OBJECTIVES: To review the cause, management and outcome in cats with septic peritonitis within the United Kingdom (2008 to 2018) and to identify if previously identified prognostic factors were associated with survival in this population. MATERIALS AND METHODS: Clinical records from 10 referral hospitals in United Kingdom were reviewed. Data collected included signalment, clinicopathological data and management techniques. Serum albumin, glucose, lactate and ionised calcium concentration; presence of intraoperative hypotension and correct empirical antibiosis were analysed via logistic regression for association with survival. RESULTS: Ninety-five cats were included. The overall survival rate was 66%. Lethargy (89%) and anorexia (75%) were the most common clinical signs, with abdominal pain and vomiting in 44% and 27% of cases, respectively. Gastro-intestinal leakage was the most common source of contamination. The presence of an abdominal mass on clinical examination was not strongly predictive of the presence of neoplasia on histology and did not confer a worse prognosis. Cats presenting with dehiscence of a previous enterotomy/enterectomy did not have a worse prognosis than those presenting with other aetologies. Intraoperative hypotension (adjusted odds ratio 0.173, 95% confidence intervals 0.034 to 0.866, P=0.033) was associated with non-survival. Cats that survived beyond 1 day postoperatively had an improved likelihood of survival (87.5%). All cats that survived beyond 6 days were successfully discharged. CLINICAL SIGNIFICANCE: This study describes the largest group of cats with septic peritonitis with an overall survival rate of 66%. The presence of an abdominal mass on clinical examination or having dehiscence of a previous gastrointestinal surgery did not confer a worse prognosis.
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Enfermedades de los Gatos , Procedimientos Quirúrgicos del Sistema Digestivo , Peritonitis , Animales , Enfermedades de los Gatos/cirugía , Gatos , Procedimientos Quirúrgicos del Sistema Digestivo/veterinaria , Peritonitis/cirugía , Peritonitis/veterinaria , Pronóstico , Estudios Retrospectivos , Reino Unido/epidemiologíaRESUMEN
Cupping therapy (CT) represents a cornerstone of traditional Chinese and Persian medicine, but it has its roots in the history of therapy. Although its exact mechanisms of action have been not fully understood, it is widely used as an alternative or complementary treatment of a broad spectrum of diseases, mainly musculoskeletal pain and muscular tension. Some practitioners use CT to cure dermatoses, but the most common adverse events occur at the skin level. We describe a case and briefly review the related literature.
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Ventosaterapia , Dolor Musculoesquelético/tratamiento farmacológico , Adulto , Humanos , Masculino , Dolor Musculoesquelético/diagnósticoRESUMEN
OBJECTIVE: Head and neck region is involved in a high percentage of malignant lesions, and oral squamous cell carcinoma (OSCC) is undoubtedly the most frequently found, accounting for over 90% of malignant tumors. Hormone receptor overexpression, like Estrogen Receptor (ER), Progesterone Receptor (PR) and Endothelial Growth Factor Receptor (EGFR), and signaling have been related to the pathogenesis of OSCC. For metastasis of OSCC, Cancer Stem Cells (CSCs) undergo epithelial to mesenchymal transition (EMT) under the influence of growth factors, cytokines, and regulation of cadherins from the tumor's microenvironment. In this context, the stem cells may become a potential therapeutic target for OSCC through modulation of cytokines and RAS pathway, which is involved in intracell signal transduction. The objective of this study was to suggest an experimental steroidogenic model for OSCC in translational research. PATIENTS AND METHODS: Dental-derived Stem Cells (D-dSCs) have been obtained from apical papilla tissue that surrounds the developing tooth of healthy donors and cultured in vitro. The cells have been exposed to different concentrations of Estradiol (E2 - 10 nM and 40 nM) in order to verify their response. The number of cells and cell viability has been evaluated up to 96 hours of treatment. RESULTS: The results showed that cell growth was increased under estradiol treatments compared with cells maintained without estradiol. Moreover, no significant difference in cell death levels was detected among treatments. CONCLUSIONS: This work underlines as D-dSCs could represent a useful steroidogenic model for the development of the target and gene therapies in OSCC.
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Carcinoma de Células Escamosas/patología , Estradiol/farmacología , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Papila Dental/citología , Receptor alfa de Estrógeno/metabolismo , Humanos , Neoplasias de la Boca/metabolismo , Células Madre/citología , Células Madre/metabolismoRESUMEN
RESUMEN El Hidradenoma nodular maligno o Hidradenocarcinoma es un tumor poco frecuente, derivado de las glándulas sudoríparas ecrinas. Puede surgir de novo o por la transformación de su contraparte benigna. Estos tumores son de crecimiento lento, comportamiento agresivo, con alta incidencia de recurrencias y posibilidad de metástasis. Su prevalencia es en la población adulta, y su pronóstico, incierto. El tratamiento de elección de estos tumores es la escisión quirúrgica con márgenes amplios.
ABSTRACT The Malignant nodular Hydradenoma or Hydradenocarcinoma is a rare tumor, derived from the eccrine sweat glands, may arise de novo or by the transformation of its benign counterpart. These tumors are slow growing, aggressive behavior, with a high incidence of recurrences and the possibility of metastasis; its prevalence being in the adult population, and its prognosis is uncertain. The treatment of choice for these tumors is surgical excision with wide margins.
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Visceral artery aneurysms are very rare and aneurysms of the celiac trunk are the rarest ones: they are in most cases asymptomatic and their detection is frequently incidental. In this article we report the case of a man affected by severe abdominal pain with a huge aneurysm of the celiac trunk, first successfully treated with coil embolization, but, after 10 months, another endovascular embolization was required for deployment of the metallic coils previously released, ahead into the fund of the sac with recanalization of the aneurysm. A second endovascular treatment was performed with other coils and Amplatzer-Plug. The high risk of rupture makes treatment of such aneurysms mandatory and surgery is still considered the gold standard therapy of VAA, but, due to its high morbidity and mortality risks, in the last years, it has been widely replaced by endovascular embolization. An effective endovascular embolization requires not only the complete filling of the aneurysmal sac, but also the complete vascular exclusion of its in-flow and out-flow tracts, to reduce the risk of its anterograde or retrograde reperfusion.
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INTRODUCTION: The objectives of this study are: (1) comparison of long-term outcomes after correction of severe gynecomastia using different techniques; (2) apply the Italian version of the BODY-Q; (3) present the role of intercostal perforator flap (ICAP) after massive weight loss for correction of severe gynecomastia. MATERIALS AND METHODS: Between January 2008 and March 2016, we performed surgical correction of bilateral severe gynecomastia in 80 men (160 breasts) following massive weight loss. Patients answered the Italian version of BODY-Q postoperative module. All patients had experienced substantial weight loss (> 30 kg), presented with bilateral severe tissue ptosis of the breast, follow-up of almost 2 years and had a good understanding of the Italian language, and signed consents were included in the study. The sample was studied about age, BMI, comorbidity, bariatric surgical procedure, follow-up, type of post-bariatric surgical procedure, complications and secondary procedures. RESULTS: We performed 487 severe gynecomastia corrections from 2008 to 2016; 80 patients adhered to the inclusion criteria and formed our study group. This cross-sectional study compared three cohorts: 52 access using a circumareolar scar, 18 with an inframammary fold scar, 10 with an inframammary fold scar using intercostal perforator flaps. There were 16 secondary procedures in group one, 2 in group two and 1 in group three. We compared the secondary procedures of group 1 with the other groups, and we obtained a significant difference with a P = 0.04. The mean patient age was 36.5 years, and the average body mass index was 27.5 kg/m2 at the time of surgical correction of gynecomastia. From the BODY-Q analysis, the group of patients undergoing adenomammectomy with inframammary fold scar using intercostal perforator flaps has achieved significantly better results regarding the satisfaction with chest, psychosocial function, satisfaction with outcome and better body image. CONCLUSIONS: This is the first study that used the BODY-Q to analyze the correction of severe gynecomastia following massive weight loss with long-term results. The use of this patient-reported outcome measure underlined that the intercostal artery perforator flap, used in the correction of severe gynecomastia following massive weight loss, is a safe and effective technique with good outcomes and high patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Cirugía Bariátrica/métodos , Ginecomastia/cirugía , Mamoplastia/métodos , Medición de Resultados Informados por el Paciente , Colgajo Perforante/trasplante , Pérdida de Peso , Adulto , Imagen Corporal/psicología , Estudios Transversales , Bases de Datos Factuales , Estética , Ginecomastia/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/diagnóstico , Obesidad Mórbida/cirugía , Satisfacción del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Bovine tuberculosis (bTB) is a zoonosis caused mainly by Mycobacterium bovis that affects domestic and wild animals. In Brazil, there are no epidemiological studies on tuberculosis in wild animal populations and their possible role in the disease maintenance in cattle herds; thus, the aim of this study was to evaluate the occurrence of tuberculosis in wild boars in Rio Grande do Sul, southern Brazil. Tissue samples of animals hunted under government consent were submitted to histopathology and M. bovis polymerase chain reaction (PCR) as screening tests; the positive samples were subsequently submitted to bacterial isolation, the gold standard diagnosis. Eighty animals were evaluated, of which 27.9% and 31.3% showed histopathological changes and M. bovis genome presence, respectively. Moreover, 23.8% of the animals had at least one organ with isolates classified as Mycobacterium tuberculosis complex (MTC). Three hunting points were risk factors for positive results on screening tests. This study shows the occurrence of tuberculosis in a wild boars' population, and raise the possibility of these animals to play a role as disease reservoirs in southern Brazil. These results may help to improve the Brazilian tuberculosis control programme, as well as elucidate the circulation of mycobacteria in this country.
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Reservorios de Enfermedades/veterinaria , Mycobacterium bovis/aislamiento & purificación , Sus scrofa/microbiología , Enfermedades de los Porcinos/epidemiología , Tuberculosis/veterinaria , Animales , Animales Salvajes/microbiología , Brasil , ADN Bacteriano/genética , Reservorios de Enfermedades/microbiología , Femenino , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Factores de Riesgo , Porcinos , Enfermedades de los Porcinos/microbiología , Tuberculosis/epidemiología , Tuberculosis/microbiologíaRESUMEN
El síndrome de Stewart-Treves es un angiosarcoma cutáneo, poco frecuente, que se produce en pacientes con linfedema crónico. Se describe clásicamente luego de realizar mastectomía radical con vaciamiento ganglionar y/o radioterapia. Su mortalidad es elevada. Comunicamos el caso de una paciente de 76 años de edad, sometida a mastectomía radical con vaciamiento ganglionar axilar, seguido de quimioterapia y radioterapia. Consulta 13 años después por dolor intenso y lesión tumoral exofitica, ulcerada, angiomatosa, sangrante y maloliente en cara anterior del brazo izquierdo. Presentaba edema del miembro de varios años de evolución. Luego de realizar biopsia por punch de la lesión, los resultados histopatológicos resultaron compatibles con linfangiosarcoma. La familia junto con el servicio de Cirugía decide realizar la extirpación del tumor, con conservación del miembro. Falleció luego de once meses de realizado el diagnóstico de síndrome de Stewart-Treves, en nuestro Servicio.
The Stewart-Treves Syndrome is a rare cutaneous angiosarcoma, that occurs in patients with chronic lymphedema. It is classically described after performing radical mastectomy with lymph node dissection and/or radiation therapy. Its mortality is high. We have reported the case of a 76 years old patient, who underwent radical mastectomy with axillary lymph node dissection, followed by chemotherapy and radiotherapy. She came 13 years later with an intense pain and exophytic, ulcerated, angiomatous, bleeding and smelly tumor injury in front side of the left arm. She had an edema of the left upper limb with several years of evolution. After performing punch biopsy of the lesion the histopathological results were compatible with lymphangiosarcoma. The family, jointly with the surgery service decided to remove the tumor with limb preservation. She died 11 months after the diagnosis of Stewart-Treves syndrome, performed in our department.
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INTRODUCTION: Occult hepatitis B infection (OBI), a virological condition characterized by a low release of Hepatitis B Virus (HBV) from liver cells and low HBV-DNA levels in serum and/or liver tissue of HBsAg-negative subjects, may reactivate in oncohematological patients undergoing immunosuppression by aggressive chemotherapy or hematopoietic stem cell transplantation. The entity of OBI reactivation varies from an increase in HBV replication without liver damage to an active HBV replication followed by liver cell necrosis, frequently severe and in some cases life threatening. Because of a possible severe outcome associated with OBI reactivation (hepatic failure or death due to the discontinuation of chemotherapy), prophylaxis with anti-HBV nucleot(s)ide analogues is recommended in relation to the foreseeable degree of immunosuppression. MATERIALS AND METHODS: This review article focuses on the clinical impact of OBI in the oncohematological setting and is addressed to all health care workers having in care oncohematological patients or involved in the treatment of HBV infection and OBI prophylaxis. CONCLUSION: International guidelines have indicated lamivudine prophylaxis in hematopoietic stem cell transplantation and when high-dose corticosteroids or anti-CD20 or anti-CD52 monoclonal antibodies are used. Entecavir or tenofovir should replace lamivudine for patients with advanced liver diseases for whom reactivation of OBI may be life threatening. When anti-CD20 or anti-CD52 sparing schedules or other non-aggressive chemotherapies are used, monitoring may be indicated, but very early treatment with highly effective antiviral drugs (entecavir or tenofovir) should be administered once a reactivation of OBI has occurred.
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Antivirales/uso terapéutico , Virus de la Hepatitis B/fisiología , Hepatitis B/tratamiento farmacológico , Antivirales/farmacología , Progresión de la Enfermedad , Hepatitis B/diagnóstico , Hepatitis B/virología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/inmunología , Humanos , Terapia de Inmunosupresión , Hígado/virología , Factores de Riesgo , Resultado del Tratamiento , Activación ViralRESUMEN
All languages, both spoken and signed, make a formal distinction between two types of terms in a proposition--terms that identify what is to be talked about (nominals) and terms that say something about this topic (predicates). Here we explore conditions that could lead to this property by charting its development in a newly emerging language--Nicaraguan Sign Language (NSL). We examine how handshape is used in nominals vs. predicates in three Nicaraguan groups: (1) homesigners who are not part of the Deaf community and use their own gestures, called homesigns, to communicate; (2) NSL cohort 1 signers who fashioned the first stage of NSL; (3) NSL cohort 2 signers who learned NSL from cohort 1. We compare these three groups to a fourth: (4) native signers of American Sign Language (ASL), an established sign language. We focus on handshape in predicates that are part of a productive classifier system in ASL; handshape in these predicates varies systematically across agent vs. no-agent contexts, unlike handshape in the nominals we study, which does not vary across these contexts. We found that all four groups, including homesigners, used handshape differently in nominals vs. predicates--they displayed variability in handshape form across agent vs. no-agent contexts in predicates, but not in nominals. Variability thus differed in predicates and nominals: (1) In predicates, the variability across grammatical contexts (agent vs. no-agent) was systematic in all four groups, suggesting that handshape functioned as a productive morphological marker on predicate signs, even in homesign. This grammatical use of handshape can thus appear in the earliest stages of an emerging language. (2) In nominals, there was no variability across grammatical contexts (agent vs. no-agent), but there was variability within- and across-individuals in the handshape used in the nominal for a particular object. This variability was striking in homesigners (an individual homesigner did not necessarily use the same handshape in every nominal he produced for a particular object), but decreased in the first cohort of NSL and remained relatively constant in the second cohort. Stability in the lexical use of handshape in nominals thus does not seem to emerge unless there is pressure from a peer linguistic community. Taken together, our findings argue that a community of users is essential to arrive at a stable nominal lexicon, but not to establish a productive morphological marker in predicates. Examining the steps a manual communication system takes as it moves toward becoming a fully-fledged language offers a unique window onto factors that have made human language what it is.
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Lenguaje , Aprendizaje , Personas con Deficiencia Auditiva , Lengua de Signos , Adulto , Femenino , Humanos , Masculino , Nicaragua , Adulto JovenRESUMEN
Languages have diverse strategies for marking agentivity and number. These strategies are negotiated to create combinatorial systems. We consider the emergence of these strategies by studying features of movement in a young sign language in Nicaragua (NSL). We compare two age cohorts of Nicaraguan signers (NSL1 and NSL2), adult homesigners in Nicaragua (deaf individuals creating a gestural system without linguistic input), signers of American and Italian Sign Languages (ASL and LIS), and hearing individuals asked to gesture silently. We find that all groups use movement axis and repetition to encode agentivity and number, suggesting that these properties are grounded in action experiences common to all participants. We find another feature - unpunctuated repetition - in the sign systems (ASL, LIS, NSL, Homesign) but not in silent gesture. Homesigners and NSL1 signers use the unpunctuated form, but limit its use to No-Agent contexts; NSL2 signers use the form across No-Agent and Agent contexts. A single individual can thus construct a marker for number without benefit of a linguistic community (homesign), but generalizing this form across agentive conditions requires an additional step. This step does not appear to be achieved when a linguistic community is first formed (NSL1), but requires transmission across generations of learners (NSL2).
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Depression is a common brain disorder affecting about 350 million people worldwide. Although the pharmacological treatment currently available can produce benefits in the majority of cases, residual depressive symptoms, cognitive deficits, functional impairment, and increase in frequency of relapses are frequently present in unipolar and bipolar depressed patients correctly treated. In the last years, numerous evidences have demonstrated the involvement of endocannabinoid system in the pathophysiology of mood disorders. Considering the recent findings about the antidepressant effect of palmitoylethanolamide in animal model, we have hypothesized the potential antidepressant effect of this fatty acid amide in unipolar and bipolar depressed patients.
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Depresión/tratamiento farmacológico , Endocannabinoides/uso terapéutico , Etanolaminas/uso terapéutico , Ácidos Palmíticos/uso terapéutico , Amidas , Humanos , Modelos TeóricosRESUMEN
Although monitoring tuberculosis (TB) infection during long-term treatment with tumour necrosis factor (TNF) antagonists is of great importance, no monitoring strategy has yet proved successful. Indeed, even the newly proposed interferon-gamma release assays (IGRAs) are known to produce dynamic changes in IFN-γ plasma levels, making them unreliable indicators of patients' pathological/clinical status. We used intracellular cytokine flow cytometry (ICCFC) to investigate the performance of multi-functional CD4(+) T cells producing IFN-γ, interleukin (IL)-2 and/or TNF in response to Mycobacterium tuberculosis-specific antigens in subjects treated with TNF antagonists. Patients were classified into three groups based on their TB status before commencement of treatment and on IFN-γ level fluctuations evaluated by IGRA during a 36-month follow-up period. The cytokine profile of M. tuberculosis-specific CD4(+) T cells showed that latent tuberculosis infection (LTBI) subjects had a higher frequency of double-positive IFN-γ(+) IL-2(+) CD4(+) T cells and triple-positive IFN-γ(+) IL-2(+) TNF(+) CD4(+) T cells compared to those without LTBI, who showed IFN-γ-level fluctuations over time. In contrast, this latter group of patients showed similar proportions of cells producing IFN-γ alone, IL-2 alone and IL-2 in combination with TNF in response to M. tuberculosis-specific antigens. It therefore appears that patients with and without LTBI infection are characterized by different intracellular cytokine profiles. This is the first study evaluating ICCFC in patients treated with TNF antagonists, and suggests that multi-functional analysis of CD4(+) T cells could be useful for ruling out TB infection in patients classified at screening as LTBI-negative but who show IGRA fluctuations under long-term TNF antagonist treatment.
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Linfocitos T CD4-Positivos/inmunología , Tuberculosis Latente/inmunología , Adulto , Anciano , Antígenos Bacterianos/inmunología , Antituberculosos/uso terapéutico , Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Citocinas/metabolismo , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Espacio Intracelular/metabolismo , Isoniazida/uso terapéutico , Tuberculosis Latente/complicaciones , Tuberculosis Latente/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Inhibidores del Factor de Necrosis Tumoral , Factores de Necrosis Tumoral/metabolismo , Adulto JovenRESUMEN
This study investigated the immune response of broiler chickens with oral treatment of a Lactobacillus spp. pool (PL) associated with microencapsulated recombinant proteins flagellin (FliC) and the subunit B of cholera toxin (CTB). Immune responses were evaluated by measuring IgA from intestinal fluid, serum IgY, and immunostaining of CD8(+) T lymphocytes present in the cecum. The evaluations were performed on d 0, 7, 14, 21, and 28 posttreatment. A significant increase (P < 0.05) was observed in IgA levels in all immunized groups, especially 3 wk after immunization. Treatments 2 (recombinant CTB) and 3 (recombinant FliC+CTB) showed the highest concentrations. Similarly, serum concentrations IgY (µg/mL) increased along the experiment, and the means for treatments 2 and 3 showed significant differences (P < 0.05) compared with controls, reaching concentrations of 533 and 540 µg/mL, respectively. The number of CD8(+) T lymphocytes in all treatments greatly differed (P < 0.05) compared with the negative control at 21 d posttreatment. However, only treatment 2 (recombinant CTB), 4 (PL), and 5 (recombinant FliC+ recombinant CTB + PL) remained significantly (P < 0.05) different from the control at 28 d posttreatment. Thus, it is concluded that the microencapsulated recombinant proteins administered orally to broiler chickens are capable of stimulating humoral and cellular immune response, and the combinations of these antigens with Lactobacillus spp. can influence the population of CD8(+) T cells residing in the cecum.