Evaluation of a polarization-enhanced laparoscopy prototype for improved intra-operative visualization of peritoneal metastases.

Despite careful staging, the accuracy for preoperative detection of small distant metastases remains poor, creating a clinical need for enhanced operative staging to detect occult peritoneal metastases. This study evaluates a polarization-enhanced laparoscopy (PEL) prototype and assesses its potential for label-free contrast enhancement of peritoneal metastases. This is a first-in-human feasibility study, including 10 adult patients who underwent standard staging laparoscopy (SSL) for gastrointestinal malignancy along with PEL. Image frames of all detectable peritoneal lesions underwent analysis. Using Monte Carlo simulations, contrast enhancement based on the color dependence of PEL (mPEL) was assessed. The prototype performed safely, yet with limitations in illumination, fogging of the distal window, and image co-registration. Sixty-five lesions (56 presumed benign and 9 presumed malignant) from 3 patients represented the study sample. While most lesions were visible under human examination of both SSL and PEL videos, more lesions were apparent using SSL. However, this was likely due to reduced illumination under PEL. When controlling for such effects through direct comparisons of integrated (WLL) vs differential (PEL) polarization laparoscopy images, we found that PEL imaging yielded an over twofold Weber contrast enhancement over WLL. Further, enhancements in the discrimination between malignant and benign lesions were achieved by exploiting the PEL color contrast to enhance sensitivity to tissue scattering, influenced primarily by collagen. In conclusion, PEL appears safe and easy to integrate into the operating room. When controlling for the degree of illumination, image analysis suggested a potential for mPEL to provide improved visualization of metastases.

Tuberculosis treatment without rifampin in kidney/kidney-pancreas transplantation: A case series report.

BACKGROUND: The best approach to tuberculosis (TB) treatment in transplanted patients is still unknown. Current guidelines are based on evidence either extrapolated from other populations or observational. Rifampin-containing regimens have strong pharmacokinetic interactions with immunosuppressive regimens, with high rates of organ dysfunction and ∼20% mortality. This report describes the results obtained using non-rifampin-containing regimens to treat confirmed TB in adult patients with kidney/kidney-pancreas transplantation. METHODS: Retrospective data analysis from confirmed TB cases in adult kidney/kidney-pancreas transplant recipients (2006-2019), treated "de novo" with non-rifampin-containing regimens. RESULTS: Fifty-seven patients had confirmed TB. Thirty patients were treated "de novo" with non-rifampin-containing regimens. These patients' mean age was 49.24 (±11.50) years. Induction immunosuppression was used in 22 patients. Maintenance immunosuppression was tacrolimus-mycophenolate-steroids in 13 (43%), sirolimus-mycophenolate-steroids in 6 (20%), and other immunosuppressive regimens in 11 (36%). Belatacept was used in four patients. TB localizations: pulmonary 43%; disseminated 23%; extrapulmonary 33%. Twenty-seven (90%) patients completed treatment with isoniazid, ethambutol, and levofloxacin (12 months, 23; 9 months, 3; 6 months, 1); 12 of these patients also received pyrazinamide for the first 2 months and were cured with functioning grafts. One patient (3%) lost the graft while on treatment. Two patients (7%) died while on TB treatment. Median (range) follow-up after completion of TB treatment was 32 (8-150) months. No TB relapses were observed. CONCLUSIONS: Results with non-rifampin-containing TB treatments in this case series were better (in terms of mortality and graft dysfunction) than those previously described with rifampin-containing regimens in transplanted patients.

Incidencia de trombosis venosa profunda en pacientes con síndrome de distrés respiratorio agudo secundario a COVID-19, bajo tromboprofilaxis con dosis intermedia de heparina de bajo peso molecular / Deep venous thrombosis incidence in patients with COVID-19 acute respiratory distress syndrome, under intermediate dose of chemical thromboprophylaxis

Resumen A pesar de la tromboprofilaxis estándar, el diagnóstico de trombosis es común en pacientes críticos con COVID-19. El objetivo del presente estudio fue evaluar la incidencia de trombosis venosa profunda (TVP) en pacientes con neumonía grave por COVID-19 con requerimientos de asistencia respiratoria mecánica, bajo tromboprofilaxis química con dosis intermedia (1 mg/kg/día) de heparina de bajo peso molecular (enoxaparina). Se trató de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Se realizó búsqueda activa y sistemática de TVP en miembros inferiores (o en confluente yúgulosubclavio en su defecto) mediante doppler venoso cada 7 días. Se continuó con la evaluación por doppler semanal hasta la finalización de la ventilación mecánica, el cum plimiento de los 28 días de internación en unidad de cuidados intensivos, el fallecimiento o la suspensión de la tromboprofilaxis con enoxaparina por cualquier causa. Se incluyeron 46 pacientes. Se realizó diagnóstico de TVP en 5 (3 en miembros inferiores y 2 en con fluente yúgulosubclavio). Tres diagnósticos de TVP fueron asociados a la presencia de catéter venoso central (2 en miembros inferiores y 1 en el confluente yúgulosubclavio), dos fallecieron durante el seguimiento por causas vinculadas al síndrome de distrés respiratorio agudo (SDRA) pero no por eventos trombóticos o de sangrado mayor. En todos los casos, los eventos trombóticos fueron asintomáticos. En nuestra serie de pacientes con SDRA moderado/grave secundario a neumonía por COVID-19, la incidencia de TVP fue del 10.9% en aquellos bajo tromboprofilaxis con dosis intermedia (1 mg/kg/día) de enoxaparina.

Abstract Despite standard thrombo prophylaxis, venous thrombosis is common in critically ill patients with COVID-19. The objective of this study was to evaluate deep venous thrombosis (DVT) incidence in patients with severe COVID-19 pneumonia with mechanical ventilation requirements under intermediate dose of chemical thromboprophylaxis (1 mg/kg/day of enoxaparin). This was a single-center, descriptive, cross-sectional study of prospectively collected data. An active and systematic protocol with venous doppler was carried out for DVT diagnosis in lower limbs (or in jugulo-subclavian venous confluence) every 7 days. Weekly doppler evaluation was continued until the end of mechanical ventilation, up to 28 days of intensive care unit admission, until death or until the thromboprophylaxis suspension for any cause. Forty-six patients were included. DVT was diagnosed in 5 (3 in lower limbs and 2 in jugulo-subclavian conflu ent). In 3 cases, DVT was catheter-related (2 in lower limbs and 1 in jugulo-subclavian confluent), 2 died during follow-up due to acute respiratory distress syndrome (ARDS) complications without thrombotic events or major bleeding. All thrombotic events were asymptomatic. In our series of patients with moderate/severe COVID-19 ARDS, DVT incidence was 10.9% under thromboprophylaxis with intermediate dose (1 mg/kg/ day) of enoxaparin.

[Deep venous thrombosis incidence in patients with COVID-19 acute respiratory distress syndrome, under intermediate dose of chemical thromboprophylaxis]. / Incidencia de trombosis venosa profunda en pacientes con síndrome de distrés respiratorio agudo secundario a COVID-19, bajo tromboprofilaxis con dosis intermedia de heparina de bajo peso molecular.

Despite standard thromboprophylaxis, venous thrombosis is common in critically ill patients with COVID-19. The objective of this study was to evaluate deep venous thrombosis (DVT) incidence in patients with severe COVID-19 pneumonia with mechanical ventilation requirements under intermediate dose of chemical thromboprophylaxis (1 mg/kg/day of enoxaparin). This was a single-center, descriptive, cross-sectional study of prospectively collected data. An active and systematic protocol with venous doppler was carried out for DVT diagnosis in lower limbs (or in jugulo-subclavian venous confluence) every 7 days. Weekly doppler evaluation was continued until the end of mechanical ventilation, up to 28 days of intensive care unit admission, until death or until the thromboprophylaxis suspension for any cause. Forty-six patients were included. DVT was diagnosed in 5 (3 in lower limbs and 2 in jugulo-subclavian confluent). In 3 cases, DVT was catheter-related (2 in lower limbs and 1 in jugulo-subclavian confluent), 2 died during follow-up due to acute respiratory distress syndrome (ARDS) complications without thrombotic events or major bleeding. All thrombotic events were asymptomatic. In our series of patients with moderate/severe COVID-19 ARDS, DVT incidence was 10.9% under thromboprophylaxis with intermediate dose (1 mg/kg/ day) of enoxaparin.

A pesar de la tromboprofilaxis estándar, el diagnóstico de tromb osis es común en pacientes críticos con COVID-19. El objetivo del presente estudio fue evaluar la incidencia de trombosis venosa profunda (TVP) en pacientes con neumonía grave por COVID-19 con requerimientos de asistencia respiratoria mecánica, bajo tromboprofilaxis química con dosis intermedia (1 mg/kg/día) de heparina de bajo peso molecular (enoxaparina). Se trató de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Se realizó búsqueda activa y sistemática de TVP en miembros inferiores (o en confluente yúgulosubclavio en su defecto) mediante doppler venoso cada 7 días. Se continuó con la evaluación por doppler semanal hasta la finalización de la ventilación mecánica, el cum plimiento de los 28 días de internación en unidad de cuidados intensivos, el fallecimiento o la suspensión de la tromboprofilaxis con enoxaparina por cualquier causa. Se incluyeron 46 pacientes. Se realizó diagnóstico de TVP en 5 (3 en miembros inferiores y 2 en confluente yúgulosubclavio). Tres diagnósticos de TVP fueron asociados a la presencia de catéter venoso central (2 en miembros inferiores y 1 en el confluente yúgulosubclavio), dos fallecieron durante el seguimiento por causas vinculadas al síndrome de distrés respiratorio agudo (SDRA) pero no por eventos trombóticos o de sangrado mayor. En todos los casos, los eventos trombóticos fueron asintomáticos. En nuestra serie de pacientes con SDRA moderado/grave secundario a neumonía por COVID-19, la incidencia de TVP fue del 10.9% en aquellos bajo tromboprofilaxis con dosis intermedia (1 mg/kg/día) de enoxaparina.

Polarization enhanced laparoscope for improved visualization of tissue structural changes associated with peritoneal cancer metastasis.

A polarization enhanced laparoscopy (PEL) imaging system was developed to examine the feasibility of utilizing PEL to augment conventional white light laparoscopy (WLL) in the visualization of peritoneal cancer metastases. The system includes a modified tip to illuminate tissue with linearly polarized light and elements in the detection path enabling recording of corresponding images linearly co- and cross-polarized relative to the incident light. WLL and PEL images from optical tissue phantoms with features of distinct scattering cross-section confirm the enhanced sensitivity of PEL to such characteristics. Additional comparisons based on images acquired from collagen gels with different levels of fiber alignment highlight another source of PEL contrast. Finally, PEL and WLL images of ex vivo human tissue illustrate the potential of PEL to improve visualization of cancerous tissue surrounded by healthy peritoneum. Given the simplicity of the approach and its potential for seamless integration with current clinical practice, our results provide motivation for clinical translation.

Echocardiographic findings in patients under mechanical ventilation with COVID-19 acute respiratory distress syndrome / Hallazgos ecocardiográficos en pacientes bajo ventilación mecánica con síndrome de dificultad respiratoria aguda por COVID-19

Abstract Coronavirus disease 2019 (COVID-19) produces a significant burden to severely ill patients affected by acute respiratory failure. The aim of this study was to describe echocardiographic findings in a series of mechanically ventilated patients with moderate and severe acute respiratory distress syndrome (ARDS) due to COVID-19. This was a single center, descriptive and cros s-sectional study of prospectively collected data. Patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate or severe ARDS. Initial echocardiogram was performed within 7 days of intensive care unit admission and every 15 days until mechanical ventilation ended, 28 days or death. Time spent by the physician for each study was measured. Multiple echographic measurements were acquired; 33 patients were analyzed. Total number of echocardiograms performed was 76. The median imaging time required to complete a standard study was 13 [10-15] minutes. Chronic structural abnormalities were present in 16 patients (48%), being LV hypertrophy the main finding in 11 patients (33%). The most frequent acute or dynamic finding was RV enlargement (43%) when considering all echocardiograms performed from admission to day 28 of follow-up. Other findings were: pulmonary hypertension (15%), new or dynamic left ventricle (LV) regional wall motion abnormalities (15%), new or dynamic LV global contractility deterioration (6%) and hypercontractility (12%).

Resumen La enfermedad por coronavirus 2019 (COVID-19) produce una carga significativa para los pacientes gravemente enfermos afectados por insuficiencia respiratoria aguda. El objetivo de este estudio fue describir los hallazgos ecocardiográficos en una serie de pacientes ventilados mecánicamente con síndrome de dificultad respiratoria aguda (SDRA) moderado y grave debido a COVID-19. Se trata de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Los pacientes tenían una infección por el coronavirus SARS-Cov-2 y SDRA moderado o grave. El ecocardiogra ma inicial se realizó dentro de los 7 días del ingreso en la unidad de cuidados intensivos y luego cada 15 días hasta finalizar la ventilación mecánica, 28 días o fallecimiento. Se midió el tiempo empleado por el operador en cada estudio. Se adquirieron múltiples medidas ecográficas. Se analizaron 33 pacientes. El número total de ecocardiogramas realizados fue de 76. El tiempo necesario (mediana [RIQ]) para la obtención de las imágenes de un estudio estándar fue de 13 [10-15] minutos. Las anomalías estructurales crónicas estuvieron presentes en 16 pacientes (48%), siendo la hipertrofia ventricular izquierda la principal (11 pacientes, 33%). El hallazgo agudo o dinámico más frecuente fue el agrandamiento del ventrículo derecho (VD) (43%) al considerar todos los ecocardiogramas realizados desde el ingreso hasta el día 28 de seguimiento. Otros hallazgos fueron: hipertensión pulmonar (15%), anomalías del movimiento de la pared regional del VI nuevas o dinámicas (15%), deterioro de la contractilidad global del ventrículo izquierdo, nuevo o dinámico (6%), e hipercontractilidad (12%).

Echocardiographic findings in patients under mechanical ventilation with COVID-19 acute respiratory distress syndrome.

Coronavirus disease 2019 (COVID-19) produces a significant burden to severely ill patients affected by acute respiratory failure. The aim of this study was to describe echocardiographic findings in a series of mechanically ventilated patients with moderate and severe acute respiratory distress syndrome (ARDS) due to COVID-19. This was a single center, descriptive and cros s-sectional study of prospectively collected data. Patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate or severe ARDS. Initial echocardiogram was performed within 7 days of intensive care unit admission and every 15 days until mechanical ventilation ended, 28 days or death. Time spent by the physician for each study was measured. Multiple echographic measurements were acquired; 33 patients were analyzed. Total number of echocardiograms performed was 76. The median imaging time required to complete a standard study was 13 [10-15] minutes. Chronic structural abnormalities were present in 16 patients (48%), being LV hypertrophy the main finding in 11 patients (33%). The most frequent acute or dynamic finding was RV enlargement (43%) when considering all echocardiograms performed from admission to day 28 of follow-up. Other findings were: pulmonary hypertension (15%), new or dynamic left ventricle (LV) regional wall motion abnormalities (15%), new or dynamic LV global contractility deterioration (6%) and hypercontractility (12%).

La enfermedad por coronavirus 2019 (COVID-19) produce una carga significativa para los pacientes gravemente enfermos afectados por insuficiencia respiratoria aguda. El objetivo de este estudio fue describir los hallazgos ecocardiográficos en una serie de pacientes ventilados mecánicamente con síndrome de dificultad respiratoria aguda (SDRA) moderado y grave debido a COVID-19. Se trata de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Los pacientes tenían una infección por el coronavirus SARS-Cov-2 y SDRA moderado o grave. El ecocardiograma inicial se realizó dentro de los 7 días del ingreso en la unidad de cuidados intensivos y luego cada 15 días hasta finalizar la ventilación mecánica, 28 días o fallecimiento. Se midió el tiempo empleado por el operador en cada estudio. Se adquirieron múltiples medidas ecográficas. Se analizaron 33 pacientes. El número total de ecocardiogramas realizados fue de 76. El tiempo necesario (mediana [RIQ]) para la obtención de las imágenes de un estudio estándar fue de 13 [10-15] minutos. Las anomalías estructurales crónicas estuvieron presentes en 16 pacientes (48%), siendo la hipertrofia ventricular izquierda la principal (11 pacientes, 33%). El hallazgo agudo o dinámico más frecuente fue el agrandamiento del ventríc ulo derecho (VD) (43%) al considerar todos los ecocardiogramas realizados desde el ingreso hasta el día 28 de seguimiento. Otros hallazgos fueron: hipertensión pulmonar (15%), anomalías del movimiento de la pared regional del VI nuevas o dinámicas (15%), deterioro de la contractilidad global del ventrículo izquierdo, nuevo o dinámico (6%), e hipercontractilidad (12%).

Decellularized extracellular matrix scaffolds identify full-length collagen VI as a driver of breast cancer cell invasion in obesity and metastasis.

The extracellular matrix (ECM), a major component of the tumor microenvironment, promotes local invasion to drive metastasis. Here, we describe a method to study whole-tissue ECM effects from disease states associated with metastasis on tumor cell phenotypes and identify the individual ECM proteins and signaling pathways that are driving these effects. We show that decellularized ECM from tumor-bearing and obese mammary glands drives TNBC cell invasion. Proteomics of the ECM from the obese mammary gland led us to identify full-length collagen VI as a novel driver of TNBC cell invasion whose abundance in tumor stroma increases with body mass index in human TNBC patients. Last, we describe the mechanism by which collagen VI contributes to TNBC cell invasion via NG2-EGFR cross-talk and MAPK signaling. Overall, these studies demonstrate the value of decellularized ECM scaffolds obtained from tissues to identify novel functions of the ECM.

Cancer cells with defective oxidative phosphorylation require endoplasmic reticulum-to-mitochondria Ca2+ transfer for survival.

Spontaneous Ca2+ signaling from the InsP3R intracellular Ca2+ release channel to mitochondria is essential for optimal oxidative phosphorylation (OXPHOS) and ATP production. In cells with defective OXPHOS, reductive carboxylation replaces oxidative metabolism to maintain amounts of reducing equivalents and metabolic precursors. To investigate the role of mitochondrial Ca2+ uptake in regulating bioenergetics in these cells, we used OXPHOS-competent and OXPHOS-defective cells. Inhibition of InsP3R activity or mitochondrial Ca2+ uptake increased α-ketoglutarate (αKG) abundance and the NAD+/NADH ratio, indicating that constitutive endoplasmic reticulum (ER)-to-mitochondria Ca2+ transfer promoted optimal αKG dehydrogenase (αKGDH) activity. Reducing mitochondrial Ca2+ inhibited αKGDH activity and increased NAD+, which induced SIRT1-dependent autophagy in both OXPHOS-competent and OXPHOS-defective cells. Whereas autophagic flux in OXPHOS-competent cells promoted cell survival, it was impaired in OXPHOS-defective cells because of inhibition of autophagosome-lysosome fusion. Inhibition of αKGDH and impaired autophagic flux in OXPHOS-defective cells resulted in pronounced cell death in response to interruption of constitutive flux of Ca2+ from ER to mitochondria. These results demonstrate that mitochondria play a fundamental role in maintaining bioenergetic homeostasis of both OXPHOS-competent and OXPHOS-defective cells, with Ca2+ regulation of αKGDH activity playing a pivotal role. Inhibition of ER-to-mitochondria Ca2+ transfer may represent a general therapeutic strategy against cancer cells regardless of their OXPHOS status.

[Strongyloides hyperinfection in patient from Patagonia with HTLV-1 co-infection]. / Hiperinfección por Strongyloides en paciente de la Patagonia con co-infección por HTLV-1.

Strongylodiasis is an unattended condition caused by the parasite Strongyloides stercoralis. The Strongyloides hyperinfection syndrome can develop in immunosuppressed hosts, mainly in those with depression of cellular immunity. Co-infection with human T-cell lymphotropic virus (HTLV) is a risk factor for the development of severe forms of strongyloidiasis. We present the case of a 50-year-old man with Strongyloides hyperinfection and coinfection with HTLV. The diagnosis was delayed owing to its unusual epidemiology and an initial suspicion of inflammatory bowel disease. Identification of the parasite in bronchioalveolar lavage and duodenal and colonic mucosa biopsies confirmed the diagnosis. Subcutaneous ivermectin was used as an anthelmintic treatment with an adequate therapeutic response.

La estrongiloidiasis es una afección desatendida causada por el parásito Strongyloides stercoralis. En los individuos inmunosuprimidos, fundamentalmente en los que tienen depresión de la inmunidad celular, puede desarrollarse el síndrome de hiperinfección por Strongyloides. La coinfección con virus linfotrópico de células T humanas (HTLV) es un factor de riesgo para el desarrollo de formas graves de estrongiloidiasis. Presentamos el caso de un hombre de 50 años con hiperinfección por Strongyloides y coinfección con HTLV. Se demoró el diagnóstico debido a su epidemiología inusual y a la sospecha inicial de enfermedad inflamatoria intestinal. El diagnóstico se confirmó mediante la identificación del parásito en muestras de lavado bronquio-alveolar y biopsias de mucosa duodenal y colónica. Se utilizó ivermectina subcutánea como tratamiento antihelmíntico con adecuada respuesta terapéutica.

Hiperinfección por Strongyloides en paciente de la Patagonia con co-infección por HTLV-1 / Strongyloides hyperinfection in patient from Patagonia with HTLV-1 co-infection

La estrongiloidiasis es una afección desatendida causada por el parásito Strongyloides stercoralis. En los individuos inmunosuprimidos, fundamentalmente en los que tienen depresión de la inmunidad celular, puede desarrollarse el síndrome de hiperinfección por Strongyloides. La coinfección con virus linfotrópico de células T humanas (HTLV) es un factor de riesgo para el desarrollo de formas graves de estrongiloidiasis. Presentamos el caso de un hombre de 50 años con hiperinfección por Strongyloides y coinfección con HTLV. Se demoró el diagnóstico debido a su epidemiología inusual y a la sospecha inicial de enfermedad inflamatoria intestinal. El diagnóstico se confirmó mediante la identificación del parásito en muestras de lavado bronquio-alveolar y biopsias de mucosa duodenal y colónica. Se utilizó ivermectina subcutánea como tratamiento antihelmíntico con adecuada respuesta terapéutica.

Strongylodiasis is an unattended condition caused by the parasite Strongyloides stercoralis. The Strongyloides hyperinfection syndrome can develop in immunosuppressed hosts, mainly in those with depression of cellular immunity. Co-infection with human T-cell lymphotropic virus (HTLV) is a risk factor for the development of severe forms of strongyloidiasis. We present the case of a 50-year-old man with Strongyloides hyperinfection and coinfection with HTLV. The diagnosis was delayed owing to its unusual epidemiology and an initial suspicion of inflammatory bowel disease. Identification of the parasite in bronchioalveolar lavage and duodenal and colonic mucosa biopsies confirmed the diagnosis. Subcutaneous ivermectin was used as an anthelmintic treatment with an adequate therapeutic response.

Functional and Sustainable 3D Human Neural Network Models from Pluripotent Stem Cells.

Three-dimensional in vitro cell culture models, particularly for the central nervous system, allow for the exploration of mechanisms of organ development, cellular interactions, and disease progression within defined environments. Here we describe the development and characterization of three-dimensional tissue models that promote the differentiation and long-term survival of functional neural networks. These tissue cultures show diverse cell populations including neurons and glial cells (astrocytes) interacting in 3D with spontaneous neural activity confirmed through electrophysiological recordings and calcium imaging over at least 8 months. This approach allows for the direct integration of pluripotent stem cells into the 3D construct bypassing early neural differentiation steps (embryoid bodies and neural rosettes), which streamlines the process while also providing a system that can be manipulated to support a variety of experimental applications. This tissue model has been tested in stem cells derived from healthy individuals as well as Alzheimer's and Parkinson's disease patients, with similar growth and gene expression responses indicating potential use in the modeling of disease states related to neurodegenerative diseases.

UV and NIR-Responsive Layer-by-Layer Films Containing 6-Bromo-7-hydroxycoumarin Photolabile Groups.

This paper describes polyelectrolyte multilayer films prepared by the layer-by-layer (LbL) technique capable of undergoing dissolution upon exposure to either ultraviolet or near-infrared light. Film dissolution is driven by photochemical deprotection of a random methacrylic copolymer with two types of side chains: (i) 6-bromo-7-hydroxycoumarinyl esters, photocleavable groups that are known to have substantial two-photon photolysis cross sections, and (ii) cationic residues from the commercially available monomer N,N-dimethylaminoethyl methacrylate (DMAEMA). In addition, the dependence of stability of both unirradiated and irradiated films on pH provides experimental evidence for the necessity of disrupting both ion-pairing and hydrophobic interactions between polyelectrolytes to realize film dissolution. This work therefore provides both new fundamental insight regarding photolabile LbL films and expands their applied capabilities to nonlinear photochemical processes.

[Clinical manifestations of organizing pneumonia]. / Manifestaciones clínicas de la neumonía en organización.

Organizing pneumonia is a clinical entity asociated with nonspecific symptoms and radiological findings and abnormalities in pulmonary function tests. It is defined by the characteristic histopathological pattern: filling of alveoli and respiratory bronchioles by plugs of granulation tissue. It can be idiopathic (COP) or secondary to other causes (SOP). It is an unusual finding and the clinical and radiographic findings are nonspecific. For specific diagnosis an invasive procedure has to be done, but often empirical treatment is started when there's a clinical suspicion. We describe the clinical characteristics of 13 patients with histological diagnosis of organizing pneumonia. Data was obtained from their medical records. The median age was 76 years and the median time to diagnosis from the onset of symptoms was 31 days. In 10 cases the diagnosis was made by transbronchial biopsy. 8 patients required hospitalization, 4 of them received high doses of steroids and 3 required ventilatory support. One patient died from a cause attributable to this entity and 5 relapsed. Dyspnea, cough and fever were the most frequent symptoms. Most patients had more than one tomographic pattern being the most common ground glass opacities and alveolar consolidation. Nine patients were diagnosed with COP and 4 with SOP. The most frequent underlying cause of SOP was drug toxicity. The clinical characteristics of the reported cases are consistent with previously published series. As an interesting feature, there was a group of patients that needed high doses of steroids and ventilatory support.

Manifestaciones clínicas de la neumonía en organización / Clinical manifestations of organizing pneumonia

La neumonía en organización es una entidad clínica asociada a síntomas y hallazgos radiológicos inespecíficos y anomalías en las pruebas de función pulmonar. El patrón histopatológico característico se define por tapones intra-alveolares de tejido de granulación. Puede presentarse sin una etiología determinada -neumonía en organización criptogénica (COP, cryptogenic organizing pneumonia)- o en otra condición clínica -neumonía en organización secundaria (SOP: secondary organizing pneumonia). Es poco frecuente y las manifestaciones clínico-radiológicas son poco específicas. Para su confirmación se requieren procedimientos invasivos, siendo habitual el tratamiento empírico con esteroides sistémicos ante la sospecha clínica. Se presentan 13 casos con diagnóstico histológico de neumonía en organización describiendo las características clínicas. La mediana de edad fue 76 años y la de tiempo al diagnóstico desde el inicio de los síntomas: 31 días. En 10 casos el diagnóstico fue por biopsia transbronquial (BTB). Ocho pacientes requirieron internación, 4 de ellos recibieron pulsos de esteroides y soporte ventilatorio. Uno falleció por una causa atribuible a la entidad y 5 presentaron recaídas. Disnea, tos y fiebre fueron los síntomas más frecuentes. La mayoría presentó más de un patrón tomográfico, siendo los más habituales vidrio esmerilado y consolidación alveolar. En 9 se realizó el diagnóstico de COP y en 4 de SOP. La causa secundaria en todos los casos fue toxicidad por drogas. Las características clínicas de los casos comunicados son consistentes con las series previamente publicadas. Cabe destacar la necesidad de tratamiento con dosis altas de esteroides y soporte ventilatorio en un grupo de pacientes.

Organizing pneumonia is a clinical entity asociated with nonspecific symptoms and radiological findings and abnormalities in pulmonary function tests. It is defined by the characteristic histopathological pattern: filling of alveoli and respiratory bronchioles by plugs of granulation tissue. It can be idiopathic (COP) or secondary to other causes (SOP). It is an unusual finding and the clinical and radiographic findings are nonspecific. For specific diagnosis an invasive procedure has to be done, but often empirical treatment is started when there’s a clinical suspicion. We describe the clinical characteristics of 13 patients with histological diagnosis of organizing pneumonia. Data was obtained from their medical records. The median age was 76 years and the median time to diagnosis from the onset of symptoms was 31 days. In 10 cases the diagnosis was made by transbronchial biopsy. 8 patients required hospitalization, 4 of them received high doses of steroids and 3 required ventilatory support. One patient died from a cause attributable to this entity and 5 relapsed. Dyspnea, cough and fever were the most frequent symptoms. Most patients had more than one tomographic pattern being the most common ground glass opacities and alveolar consolidation. Nine patients were diagnosed with COP and 4 with SOP. The most frequent underlying cause of SOP was drug toxicity. The clinical characteristics of the reported cases are consistent with previously published series. As an interesting feature, there was a group of patients that needed high doses of steroids and ventilatory support.

Noninvasive assessment of mitochondrial organization in three-dimensional tissues reveals changes associated with cancer development.

Mitochondrial organization is often altered to accommodate cellular bioenergetic and biosynthetic demands. Changes in metabolism are a hallmark of a number of diseases, including cancer; however, the interdependence between mitochondrial metabolic function and organization is not well understood. Here, we present a noninvasive, automated and quantitative method to assess mitochondrial organization in three-dimensional (3D) tissues using exclusively endogenous two-photon excited fluorescence (TPEF) and show that mitochondrial organization reflects alterations in metabolic activities. Specifically, we examine the organization of mitochondria within live, engineered epithelial tissue equivalents that mimic normal and precancerous human squamous epithelial tissues. We identify unique patterns of mitochondrial organization in the different tissue models we examine, and we attribute these to differences in the metabolic profiles of these tissues. We find that mitochondria are clustered in tissues with high levels of glycolysis and are more highly networked in tissues where oxidative phosphorylation is more dominant. The most highly networked organization is observed within cells with high levels of glutamine consumption. Furthermore, we demonstrate that mitochondrial organization provides complementary information to traditional morphological hallmarks of cancer development, including variations in nuclear size. Finally, we present evidence that this automated quantitative analysis of endogenous TPEF images can identify differences in the mitochondrial organization of freshly excised normal and pre-cancerous human cervical tissue specimens. Thus, this method could be a promising new modality to assess the role of mitochondrial organization in the metabolic activity of 3D tissues and could be further developed to serve as an early cancer clinical diagnostic biomarker.

[Inflammatory myopathy with initial respiratory muscles involvement and rheumatoid arthritis]. / Miopatía inflamatoria con compromiso inicial de músculos respiratorios y artritis reumatoidea.

Inflammatory myopathies comprise a heterogeneous group of subacute, chronic and sometimes acute acquired muscle diseases. The most common inflammatory myopathies seen in practice can be separated into four distinct subsets: polymyositis, dermatomyositis, necrotizing autoimmune myositis and inclusion body myositis. These disorders present as proximal and symmetric muscle weakness but rarely respiratory muscles may also be affected. We report the case of a 39 year-old female with inflammatory myopathy with acute respiratory failure due to alveolar hypoventilation secondary to respiratory muscle dysfunction that required mechanical ventilation. The treatment with steroids, methotrexate and intravenous immune globulin was successful as well as the implementation of non-invasive ventilation as an alternative to endotracheal intubation.

Miopatía inflamatoria con compromiso inicial de músculos respiratorios y artritis reumatoidea

Las miopatías inflamatorias constituyen un grupo heterogéneo de enfermedades musculares adquiridas de presentación subaguda, crónica y a veces aguda. Las entidades clínicas más frecuentes son la dermatomiositis, la polimiositis, la miositis necrotizante autoinmune y la miositis por cuerpos de inclusión. Suelen presentarse con debilidad muscular con predominio proximal y simétrica, pero rara vez comprometen los músculos respiratorios. Presentamos el caso de una mujer de 39 años con miopatía inflamatoria inespecífica que presentó insuficiencia respiratoria secundaria a hipoventilación alveolar por debilidad muscular y requirió asistencia respiratoria mecánica. Respondió favorablemente y de forma rápida tras el tratamiento instaurado con inmunosupresores (corticoides y metotrexato) e inmunoglobulina humana endovenosa. Se utilizó ventilación no invasiva como alternativa a la intubación orotraqueal con adecuada tolerancia.(AU)

Inflammatory myopathies comprise a heterogeneous group of subacute, chronic and sometimes acute acquired muscle diseases. The most common inflammatory myopathies seen in practice can be separated into four distinct subsets: polymyositis, dermatomyositis, necrotizing autoimmune myositis and inclusion body myositis. These disorders present as proximal and symmetric muscle weakness but rarely respiratory muscles may also be affected. We report the case of a 39 year-old female with inflammatory myopathy with acute respiratory failure due to alveolar hypoventilation secondary to respiratory muscle dysfunction that required mechanical ventilation. The treatment with steroids, methotrexate and intravenous immune globulin was successful as well as the implementation of non-invasive ventilation as an alternative to endotracheal intubation.(AU)

Miopatía inflamatoria con compromiso inicial de músculos respiratorios y artritis reumatoidea

Las miopatías inflamatorias constituyen un grupo heterogéneo de enfermedades musculares adquiridas de presentación subaguda, crónica y a veces aguda. Las entidades clínicas más frecuentes son la dermatomiositis, la polimiositis, la miositis necrotizante autoinmune y la miositis por cuerpos de inclusión. Suelen presentarse con debilidad muscular con predominio proximal y simétrica, pero rara vez comprometen los músculos respiratorios. Presentamos el caso de una mujer de 39 años con miopatía inflamatoria inespecífica que presentó insuficiencia respiratoria secundaria a hipoventilación alveolar por debilidad muscular y requirió asistencia respiratoria mecánica. Respondió favorablemente y de forma rápida tras el tratamiento instaurado con inmunosupresores (corticoides y metotrexato) e inmunoglobulina humana endovenosa. Se utilizó ventilación no invasiva como alternativa a la intubación orotraqueal con adecuada tolerancia.

Inflammatory myopathies comprise a heterogeneous group of subacute, chronic and sometimes acute acquired muscle diseases. The most common inflammatory myopathies seen in practice can be separated into four distinct subsets: polymyositis, dermatomyositis, necrotizing autoimmune myositis and inclusion body myositis. These disorders present as proximal and symmetric muscle weakness but rarely respiratory muscles may also be affected. We report the case of a 39 year-old female with inflammatory myopathy with acute respiratory failure due to alveolar hypoventilation secondary to respiratory muscle dysfunction that required mechanical ventilation. The treatment with steroids, methotrexate and intravenous immune globulin was successful as well as the implementation of non-invasive ventilation as an alternative to endotracheal intubation.

Miopatía inflamatoria con compromiso inicial de músculos respiratorios y artritis reumatoidea. / [Inflammatory myopathy with initial respiratory muscles involvement and rheumatoid arthritis].

Inflammatory myopathies comprise a heterogeneous group of subacute, chronic and sometimes acute acquired muscle diseases. The most common inflammatory myopathies seen in practice can be separated into four distinct subsets: polymyositis, dermatomyositis, necrotizing autoimmune myositis and inclusion body myositis. These disorders present as proximal and symmetric muscle weakness but rarely respiratory muscles may also be affected. We report the case of a 39 year-old female with inflammatory myopathy with acute respiratory failure due to alveolar hypoventilation secondary to respiratory muscle dysfunction that required mechanical ventilation. The treatment with steroids, methotrexate and intravenous immune globulin was successful as well as the implementation of non-invasive ventilation as an alternative to endotracheal intubation.