Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of PDT and topical angiogenic inhibitor for treatment of port wine stain (PWS) birthmarks: a novel approach

Port wine stain (PWS) birthmarks are a congenital cutaneous vascular malformation involving ecstatic post-capillary venules. Current standard treatment for PWS is the pulsed dye laser (PDL). Vascular-targeted photodynamic therapy (PDT) has been used for the treatment of PWS in China since the early 1990's. Both can achieve a certain degree of color blanching in various types of PWS lesions. However, the majority of PWS lesions require multiple treatments. Some PWS lesions can recur or become darker after successful treatment. Recently, it has been proposed that this phenomenon might be initiated by neoangiogenesis that can be caused by treatment via wound healing response. The combined use of photothermolysis and a topical application of an angiogenic inhibitor such as Imiquimod and Rapamycin, were evaluated in several pilot studies. It is well-known that PDT can induce various host immune responses VEGF overexpression. Recent clinical data also show that improved clinical outcomes are obtained through the combination of ocular PDT and anti-VEGF therapy. This article will discuss rationales and implications of using such a combination modality and highlight recent progress based on our clinical experience and published data.
Recombinant Bone Morphogenetic Protein-2: Clinical Use in the Treatment of Recalcitrant Nonunion and Difficult Fractures

Nonunion of both fractures and fusions can present great challenges to the practicing clinician. Although autologous bone grafting has remained the standard treatment of these problems, its use may have limitations or be contraindicated altogether. The understanding of the biology and the cascade of events that produce healing has led to the discovery of bone morphogenetic protein. Bone morphogenetic protein has been used with success in the treatment recalcitrant nonunion of long bones and joint fusions and adds to the clinical options available when autologous bone graft is not available.
Historia natural de la enfermedad vascular cerebral en el Perú

Los datos contenidos en tales fuentes documentales son analizados y expuestos en la presente publicación. La intención es proporcionar una visión, basada en evidencias, acerca de los aspectos más significativos de la historia natural de la EVC en nuestro país. Obviamente, el material revisado, puede ser sesgado, desde el punto de vista epidemiológico, por tratarse de una muestra exclusivamente hospitalaria. No obstante, creemos que tal error es poco significativo, por la elevada cifra de pacientes incluidos y en consecuencia nuestras conclusiones deben de ser cercanas a las de la población nacional con EVC.
3D reconstruction of anatomical structures from endoscopic images

Endoscopy is attracting increasing attention for its role in minimally invasive, computer-assisted and tele-surgery. Analyzing images from endoscopes to obtain meaningful information about anatomical structures such as their 3D shapes, deformations and appearances, is crucial to such surgical applications. However, 3D reconstruction of bones from endoscopic images is challenging due to the small field of view of the endoscope, large image distortion, featureless surfaces and occlusion by blood and particles. In this thesis, a novel methodology is developed for accurate 3D bone reconstruction from endoscopic images, by exploiting and enhancing computer vision techniques such as shape from shading, tracking and statistical modeling. We first designed a complete calibration scheme to estimate both geometric and photometric parameters including the rotation angle, light intensity and light sources’ spatial distribution. This is crucial to our further analysis of endoscopic images. A solution is presented to reconstruct the Lambertian surface of bones using a sequence of overlapped endoscopic images, where only partial boundaries are visible in each image. We extend the classical shapefrom-shading approach to deal with perspective projection and near point light sources that are not co-located with the camera center. Then, by tracking the endoscope, the complete occluding boundary of the bone is obtained by aligning the partial boundaries from different images. A complete and consistent shape is obtained by simultaneously growing the surface normals and depths in all views. Finally, in order to deal with over-smoothness and occlusions, we employ a statistical atlas to constrain and refine the multi-view shape from shading. A two-level framework is also developed for efficient atlas construction.
Time course of continuous positive airway pressure effects on central sleep apnoea in patients with chronic heart failure

Continuous positive airway pressure (CPAP) causes a variable immediate reduction in the frequency of central apnoeas and hypopnoeas in patients with congestive heart failure (CHF) and central sleep apnoea (CSA), but has beneficial mid‐term effects on factors known to destabilize the ventilatory control system. We, therefore, tested whether CPAP therapy leads, in addition to its short‐term effects on CSA, to a significant further alleviation of CSA after 12 weeks of treatment on the same CPAP level in such patients. CPAP therapy was initiated in 10 CHF patients with CSA. During the first night on CPAP, the pressure was stepwise increased to a target pressure of 8–12 cmH2O or the highest level the patients tolerated (<12 cmH2O). Throughout the second night (baseline CPAP), the achieved CPAP of the first night was applied. After 12 weeks of CPAP treatment, we performed a follow‐up polysomnography (12 weeks CPAP) on the same CPAP level (8.6 ± 1.1 cmH20). We found a significant reduction of the apnoea‐hypopnoea index (AHI) between the diagnostic polysomnography and baseline CPAP night (41.8 ± 19.2 versus 22.2 ± 12.6 events per hour; P = 0.005). The AHI further significantly decreased between the baseline CPAP night and the 12 weeks CPAP night on the same CPAP level (22.2 ± 12.6 versus 12.8 ± 11.0 events per hour; P = 0.028). We conclude that, in addition to its immediate effects, CPAP therapy leads to a time‐dependent alleviation of CSA in some CHF patients, indicating that in such patients neither clinical nor scientific decisions should be based on a short‐term trial of CPAP.
Neutrophil Elastase Differentially Regulates Interleukin 8 (IL-8) and Vascular Endothelial Growth Factor (VEGF) Production by Cigarette Smoke Extract*

Background: Interaction between oxidative stress (CSE) and protease (NE) may contribute to COPD pathogenesis. Results: Although NE enhances CSE-induced IL-8, it suppresses VEGF production, which is due to degradation by uptake of NE into bronchial epithelial cells. Conclusion: NE contributes to the pathogenesis of COPD by enhancing inflammation and apoptosis. Significance: This provides a molecular mechanism for understanding COPD pathogenesis. Inflammation by IL-8-induced neutrophil recruitment and apoptosis of epithelial cells by decreased expression of VEGF have been suggested as one of the complicated pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). The role of neutrophil elastase (NE) in the development of COPD is also well known. However, little is known about how they interact. The objective of this study was to elucidate the effect of NE on cigarette smoke extract (CSE)-induced IL-8 and VEGF production and its molecular mechanism in bronchial epithelial cells. CSE increased both IL-8 and VEGF production in human bronchial epithelial cells (BEAS-2B). Although NE significantly enhanced CSE-induced IL-8 production, it suppressed VEGF production. This differential regulation was not CSE-specific. The effect of NE on IL-8 production, but not VEGF, was ERK-dependent. Interestingly, in contrast to decreased VEGF protein expression, NE accelerated VEGF transcription by CSE, suggesting post-translational modification. When cells were incubated with purified NE, it was detected in the cytoplasm, suggesting the intracellular translocation of NE. Furthermore, NE fragmented recombinant human VEGF in vitro but not recombinant human IL-8. These results indicate that VEGF down-regulation is due to direct degradation by NE, which is translocated into cells. Similar to in vitro cell experiments, elastase treatment increased CSE-induced IL-8; however, it suppressed VEGF production in bronchoalveolar lavage fluid of CSE-treated mice. Moreover, elastase treatment enhanced CSE-induced emphysema in mice. Considering the actions of IL-8 and VEGF, our results suggest that NE contributes to the pathogenesis of COPD by enhancing inflammation and apoptosis.
Sleep onset and cardiovascular activity in primary insomnia

The transition from wakefulness to sleep is characterized typically by a shift from sympathetic to parasympathetic regulation. Physiological functions, depending on the neurovegetative system, decrease overall. Previous studies have shown cardiovascular and electroencephalographic hyperactivity during wakefulness and sleep in insomniacs compared with normal sleepers, but there is very little evidence of this in the process of sleep onset. The purpose of this study was to compare cardiovascular and autonomic responses before and after falling asleep in eight insomniacs (who met DSM‐IV criteria for primary insomnia) and eight normal sleepers. Non‐invasive measures of heart rate (HR), stroke volume (SV), cardiac output (CO) and pre‐ejection period (PEP) were collected by impedance cardiography during a night of polysomnographic recording. Frequency domain measures [low‐frequency (LF), high‐frequency (HF)] of heart rate variability (HRV) were also estimated. Decrements in HR and CO and increases in SV and HF normalized units (n.u.) were found in both groups after sleep onset compared with wakefulness. Conversely, PEP (related inversely to sympathetic β‐adrenergic activity) showed increases after sleep onset in controls, but remained unchanged in insomniacs. PEP was also significantly lower in insomniacs than in normal sleepers in both conditions. These data suggest that, whereas normal sleepers follow the expected progressive autonomic drop, constant sympathetic hyperactivation is detected in insomniacs. These results support the aetiological hypothesis of physiological hyperarousal underlying primary insomnia.
Sleep deprivation suppresses the increase of rapid eye movement density across sleep cycles

We investigated the association between rapid eye movement (REM) density (REMd) and electroencephalogram (EEG) activity during non‐rapid eye movement (NREM) and REM sleep, within the re‐assessment, in a large sample of normal subjects, of the reduction of oculomotor activity in REM sleep after total sleep deprivation (SD). Coherently with the hypothesis of a role of homeostatic sleep pressure in influencing REMd, a negative correlation between changes in REMd and slow‐wave activity (SWA) was expected. A further aim of the study was to evaluate if the decreased REMd after SD affects ultradian changes across sleep periods. Fifty normal subjects (29 male and 21 female; mean age = 24.3 ± 2.2 years) were studied for four consecutive days and nights. Sleep recordings were scheduled in the first (adaptation), second (baseline) and fourth night (recovery). After awakening from baseline sleep, a protocol of 40 h SD started at 10:00 hours. Polysomnographic measures, REMd and quantitative EEG activity during NREM and REM sleep of baseline and recovery nights were compared. We found a clear reduction of REMd in the recovery after SD, due to the lack of REMd changes across cycles. Oculomotor changes positively correlated with a decreased power in a specific range of fast sigma activity (14.75–15.25 Hz) in NREM, but not with SWA. REMd changes were also related to EEG power in the 12.75–13.00 Hz range in REM sleep. The present results confirm the oculomotor depression after SD, clarifying that it is explained by the lack of changes in REMd across sleep cycles. The depression of REMd can not simply be related to homeostatic mechanisms, as REMd changes were associated with EEG power changes in a specific range of spindle frequency activity, but not with SWA.
Sleep deprivation impairs contextual fear conditioning and attenuates subsequent behavioural, endocrine and neuronal responses

Sleep deprivation (SD) affects hippocampus‐dependent memory formation. Several studies in rodents have shown that brief SD immediately following a mild foot shock impairs consolidation of contextual fear memory as reflected in a reduced behavioural freezing response during re‐exposure to the shock context later. In the first part of this study, we examined whether this reduced freezing response is accompanied by an attenuated fear‐induced activation of the hypothalamic–pituitary–adrenal (HPA) axis. Results show that 6 h of SD immediately following the initial shock results in a diminished adrenal corticosterone (CORT) response upon re‐exposure to the shock context the next day. In the second part, we established whether the attenuated freezing response in SD animals is associated with reduced activation of relevant brain areas known to be involved in the retrieval and expression of fear memory. Immunohistochemical analysis of brain slices showed that the normal increase in phosphorylation of the transcription factor 3′,5′‐cyclic AMP response‐element binding protein (CREB) upon re‐exposure to the shock context was reduced in SD animals in the CA1 region of the hippocampus and in the amygdala. In conclusion, brief SD impairs the consolidation of contextual fear memory. Upon re‐exposure to the context, this is reflected in a diminished behavioural freezing response, an attenuated HPA axis response and a reduction of the normal increase of phosphorylated CREB expression in the hippocampus and amygdala.
Hepatic FOXO1 Target Genes Are Co-regulated by Thyroid Hormone via RICTOR Protein Deacetylation and MTORC2-AKT Protein Inhibition*

Background: Thyroid hormone (TH) and FOXO1 share similar transcriptional networks. However, TH regulation of FOXO1 activity is not well understood. Results: TH decreased RICTOR acetylation and MTORC2/AKT activity by SIRT1 activation and reduced FOXO1 phosphorylation. Conclusion: TH co-regulated transcription of FOXO1 target genes via RICTOR deacetylation. Significance: Downstream metabolic effects by TH can post-translationally activate other transcription factors. MTORC2-AKT is a key regulator of carbohydrate metabolism and insulin signaling due to its effects on FOXO1 phosphorylation. Interestingly, both FOXO1 and thyroid hormone (TH) have similar effects on carbohydrate and energy metabolism as well as overlapping transcriptional regulation of many target genes. Currently, little is known about the regulation of MTORC2-AKT or FOXO1 by TH. Accordingly, we performed hepatic transcriptome profiling in mice after FOXO1 knockdown in the absence or presence of TH, and we compared these results with hepatic FOXO1 and THRB1 (TRβ1) ChIP-Seq data. We identified a subset of TH-stimulated FOXO1 target genes that required co-regulation by FOXO1 and TH. TH activation of FOXO1 was directly linked to an increase in SIRT1-MTORC2 interaction and RICTOR deacetylation. This, in turn, led to decreased AKT and FOXO1 phosphorylation. Moreover, TH increased FOXO1 nuclear localization, DNA binding, and target gene transcription by reducing AKT-dependent FOXO1 phosphorylation in a THRB1-dependent manner. These events were associated with TH-mediated oxidative phosphorylation and NAD+ production and suggested that downstream metabolic effects by TH can post-translationally activate other transcription factors. Our results showed that RICTOR/MTORC2-AKT can integrate convergent hormonal and metabolic signals to provide coordinated and sensitive regulation of hepatic FOXO1-target gene expression.
Vibrio cholerae Porin OmpU Induces Caspase-independent Programmed Cell Death upon Translocation to the Host Cell Mitochondria*

Porins, a major class of outer membrane proteins in Gram-negative bacteria, primarily act as transport channels. OmpU is one of the major porins of human pathogen, Vibrio cholerae. In the present study, we show that V. cholerae OmpU has the ability to induce target cell death. Although OmpU-mediated cell death shows some characteristics of apoptosis, such as flipping of phosphatidylserine in the membrane as well as cell size shrinkage and increased cell granularity, it does not show the caspase-3 activation and DNA laddering pattern typical of apoptotic cells. Increased release of lactate dehydrogenase in OmpU-treated cells indicates that the OmpU-mediated cell death also has characteristics of necrosis. Further, we show that the mechanism of OmpU-mediated cell death involves major mitochondrial changes in the target cells. We observe that OmpU treatment leads to the disruption of mitochondrial membrane potential, resulting in the release of cytochrome c and apoptosis-inducing factor (AIF). AIF translocates to the host cell nucleus, implying that it has a crucial role in OmpU-mediated cell death. Finally, we observe that OmpU translocates to the target cell mitochondria, where it directly initiates mitochondrial changes leading to mitochondrial membrane permeability transition and AIF release. Partial blocking of AIF release by cyclosporine A in OmpU-treated cells further suggests that OmpU may be inducing the opening of the mitochondrial permeability transition pore. All of these results lead us to the conclusion that OmpU induces cell death in target cells in a programmed manner in which mitochondria play a central role.
Prognostic value of CD44 in renal cell carcinoma

BACKGROUND: CD44 is a transmembrane glycoprotein involved in cell-cell and cell-matrix interactions. De novo expression of CD44 and its variant isoforms has been associated with aggressive behavior in various tumors. Since little data is available on the role of CD44 expression in renal cell carcinoma, we evaluated CD44 expression to determine its prognostic value. METHODS: Forty-six patients with renal cell carcinoma were studied. CD44 expression was evaluated semiquantitively on paraffin-embedded tumor tissue by immunohistochemistry. The prognostic value of CD44 was tested using Kaplan Meier plots by the log rank test and Cox regression analysis. RESULTS: Fifteen out of 46 specimens (32.6%) were CD44-positive. According to bivariate analysis, tumor stage, tumor size, nuclear grade and CD44 expression were significant prognostic factors. CONCLUSIONS: CD44 expression can be considered as a useful prognostic parameter in renal cell carcinoma. KEY WORDS: CD44 expression, renal cell carcinoma, immunohistochemistry.
Ferropenia: Un problema ignorado

La deficiencia de hierro es la carencia nutricional mas extendida en el mundo, con serias implicaciones para la salud. Se realizo un estudio descriptivo en una muestra de 160 pacientes, con niveles sericos de hierro por debajo de 10 mmol/L, en el Hospital General Docente «Armando Enrique Cardoso», en el periodo comprendido entre enero y diciembre de 1999. Los objetivos de la investigacion fueron identificar el grupo etareo afectado por este estado carencial, asi como sus principales causas, manifestaciones clinicas y la relacion de dicho estado con la hemoglobina y el estado nutricional. Los principales resultados fueron una afectacion del 59,4 % en el grupo de 0 a 1 ano; la causa mas frecuente fue la ingestion de leche de vaca en el 43,1 % de los casos y la inapetencia fue la manifestacion que estuvo presente en el mayor numero de pacientes. Se concluye que la ferropenia es un problema frecuente, que en ocasiones es ignorado, y para su prevencion se deben cumplir algunas pautas, como es la suplementacion precoz con hierro exogeno en dosis bajas.
Comparison of various immunoassay kits for rapid screening of pandemic influenza H1N1-2009 viruses.

The success of therapeutic measures is predicted on the basis of rapid and precise diagnosis of infection. A comparison of three rapid influenza immunoassay (RIIA) kits, the Directigen Flu A+B test, QuickVue influenza A+B test and the Quick S-INFLU A.B, for detection of pandemic influenza H1N1 (2009) viruses, have been made on 105 patients with flu like syndrome. The sensitivity, specificity and ability to screen influenza type A and B viruses were evaluated. The clinical specimens detected positive by real-time RT-PCR for pandemic influenza H1N1 (2009) viruses and the reference influenza strain [A/PR/8/34 (H1N1)] were cultured in MDCK cells to determine TCID 50 and the performance of kits were compared against the current gold standard, real-time RT-PCR. The diagnostic sensitivity of Directigen kit was 10 3 TCID 50 /ml where as the QuickVue and Quick S-INFLU A.B were 10 3.5 TCID 50 /ml in case of the pandemic H1N1 viruses which was comparable to the reference H1N1 virus (10 3 TCID 50 /ml for QuickVue and Directigen and 10 3.5 TCID 50 /ml for Quick S-INFLU A.B). Our findings suggest that although RIIA kits are not as sensitive as the conventional and real-time RT-PCR yet they are very useful in preliminary bedside screening of large number of critically ill patients during pandemic situation.
Estratificación ecocardiográfica del riesgo tromboembólico en la fibrilación auricular: perfeccionamiento del índice CHA2DS2-VASc en la era de nuevos anticoagulantes orales

Departamento de Cardiología, Policlínico del Hospital Universidad de Bari MD Doctor en Medicina FESC Fellow of the European Society of Cardiology FANMCO Fellow dell’Associazione Nazionale Medici Cardiologi Ospedalieri La fibrilación auricular (FA) es la forma más frecuente de alteración sostenida del ritmo cardíaco que afecta al 1% a 2% de la población general. La FA incrementa cinco veces el riesgo de accidente cerebrovascular (ACV), atribuyéndosele uno de cada cinco de todos los tipos de ACV más un número desconocido de “ACV criptogénicos”. La incidencia media de ACV incapacitante en pacientes con FA es del 2,5%/año, y este porcentaje aumenta al 7% si se incluyen el ataque isquémico transitorio (AIT) y el ACV silencioso. Por lo tanto, el balance entre el riesgo tromboembólico y hemorrágico es esencial en el manejo de la terapia antitrombótica en pacientes con FA. La primera tarea del médico en estos pacientes es la estratificación del riesgo mediante todos los sistemas de índices disponibles. Esta es la base de la “terapia antitrombótica individualizada”, que en ciertas ocasiones persiste como un objetivo ideal, para tratar de la mejor manera la FA frente a los dos grandes riesgos: la embolia cerebral y las hemorragias mayores.
Cyclic Nucleotide-dependent Protein Kinases Target ARHGAP17 and ARHGEF6 Complexes in Platelets*

Endothelial cells release prostacyclin (PGI2) and nitric oxide (NO) to inhibit platelet functions. PGI2 and NO effects are mediated by cyclic nucleotides, cAMP- and cGMP-dependent protein kinases (PKA, PKG), and largely unknown PKA and PKG substrate proteins. The small G-protein Rac1 plays a key role in platelets and was suggested to be a target of cyclic nucleotide signaling. We confirm that PKA and PKG activation reduces Rac1-GTP levels. Screening for potential mediators of this effect resulted in the identification of the Rac1-specific GTPase-activating protein ARHGAP17 and the guanine nucleotide exchange factor ARHGEF6 as new PKA and PKG substrates in platelets. We mapped the PKA/PKG phosphorylation sites to serine 702 on ARHGAP17 using Phos-tag gels and to serine 684 on ARHGEF6. We show that ARHGAP17 binds to the actin-regulating CIP4 protein in platelets and that Ser-702 phosphorylation interferes with this interaction. Reduced CIP4 binding results in enhanced inhibition of cell migration by ARHGAP17. Furthermore, we show that ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and that ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex. PKA and PKG induced rearrangement of ARHGAP17- and ARHGEF6-associated protein complexes might contribute to Rac1 regulation and platelet inhibition.