18F-florbetapir PET as a marker of myelin integrity across the Alzheimer's disease spectrum.

PURPOSE: Recent evidence suggests that PET imaging with amyloid-ß (Aß) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer's disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aß PET, contributes to AD progression remains unexplored. METHODS: Participants with concurrent 18F-florbetapir (FBP) PET, MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 Aß-positive cognitively impaired, and 207 Aß-negative cognitively impaired subjects). A subset of these participants had also available diffusion tensor imaging (DTI) images (n = 195). We investigated cross-sectional associations of FBP retention in the white matter (WM) with MRI-based markers of WM degeneration, AD clinical progression, and fluid biomarkers. In longitudinal analyses, we used linear mixed models to assess whether FBP retention in normal-appearing WM (NAWM) predicted progression of WM hyperintensity (WMH) burden and clinical decline. RESULTS: In AD-continuum individuals, FBP retention in NAWM was (1) higher compared with WMH regions, (2) associated with DTI-based measures of WM integrity, and (3) associated with longitudinal progression of WMH burden. FBP uptake in WM decreased across the AD continuum and with increasingly abnormal CSF biomarkers of AD. Furthermore, FBP retention in the WM was associated with large-calibre axon degeneration as reflected by abnormal plasma neurofilament light chain levels. Low FBP uptake in NAWM predicted clinical decline in preclinical and prodromal AD, independent of demographics, global cortical Aß, and WMH burden. Most of these associations were also observed in Aß-negative cognitively impaired individuals. CONCLUSION: These results support the hypothesis that FBP retention in the WM is myelin-related. Demyelination levels progressed across the AD continuum and were associated with clinical progression at early stages, suggesting that this pathologic process might be a relevant degenerative feature in the disease course.

White matter hyperintensities are associated with subthreshold amyloid accumulation.

The association between white matter hyperintensities (WMH) and amyloid accumulation over time in cognitively normal, amyloid-negative elderly people remains largely unexplored. In order to study whether baseline WMH were associated with longitudinal subthreshold amyloid accumulation, 159 cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative who were amyloid-negative at baseline were examined. All the participants underwent a T1 and a Fluid-Attenuated Inversion Recovery MRI scan at baseline. Amyloid PET imaging was performed at baseline and follow-up visits in 2-year intervals for up to 8 years. Partial volume correction was applied for quantifying cortical Standardised Uptake Value Ratios (SUVR). The associations between global and regional WMH burden and amyloid accumulation were assessed using linear mixed models adjusted by demographic characteristics and baseline SUVR. Partial volume correction increased the measured annual rate of change (+2.4%) compared to that obtained from non-corrected data (+0.5%). There were no significant correlations between baseline WMHs and baseline subthreshold cortical amyloid uptake. In a longitudinal analysis, increased baseline cortical SUVR and increased baseline burden of global (p â€‹= â€‹0.006), frontal (p â€‹= â€‹0.006), and parietal WMH (p â€‹= â€‹0.003) were associated with faster amyloid accumulation. WMH-related amyloid accumulation occurred in parietal, frontal, and, to a lesser extent, cingulate cortices. These results remained unchanged after a sensitivity analysis excluding participants with the highest cortical SUVRs. This is the first study to identify a specific spatial distribution of WMH which is associated with future amyloid accumulation in cognitively normal elderly subjects without PET-detectable amyloid pathology. These findings may have important implications in prevention trials for the early identification of amyloid accumulation.

Prolonged Migraine Stuttering Aura: Structural, Functional, and Video Neuroimaging Study of an Atypical Migraine Aura. A Case Report.

BACKGROUND: Stuttering is a disorder in the rhythm of speech characterized by an involuntary repetition, prolongation, and cessation of sounds. Neurogenic acquired stuttering is a very rare disorder which could result from different conditions with the involvement of several brain locations. CASE REPORT: A 16-year-old male presented to our Hospital with headache associated with blurred vision followed by right-sided facial and upper limb tingling, clumsiness of right arm, and a complete inability to formulate language which evolved in the next minutes into an intense speech disorder characterized by persistent stuttering. Urgent brain magnetic resonance imaging showed a prominence of venous vasculature in left hemisphere in susceptibility weighted imaging sequence. A fluorodeoxyglucose-positron emission tomography revealed a bilateral occipital, temporal, and parietal hypometabolism. With the suspicion of migraine aura, analgesic treatment was administered. Symptoms progressively resolved inside 10 hours. Five months later he experienced a similar episode. CONCLUSION: This case report represents a diagnostic challenge and suggests the inclusion of stuttering within the neurological manifestations of higher cortical dysfunction that can be found as a result of migraine aura.

PET and MRI detection of early and progressive neurodegeneration in spinocerebellar ataxia type 36.

BACKGROUND: The spinocerebellar ataxias (SCAs) form a clinically, genetically, and pathological heterogeneous group of autosomal-dominant degenerative diseases. In particular, SCA36 is characterized by a late-onset, slowly progressive cerebellar syndrome typically associated with sensorineural hearing loss. This study was aimed at analyzing the neurodegenerative process underlying SCA36 through fluorodeoxyglucose positron emission tomography (FDG-PET) and MRI scans. METHODS: Twenty SCA36 patients underwent a study consisting of FDG-PET and MRI scans. Clinical motor evaluation was performed through the Scale for the Assessment and Rating of Ataxia (SARA). FDG-PET was carried out using a voxel-by-voxel and region-of-interest analysis. MRI evaluation was based on visual inspection and volumetric analysis. RESULTS: SARA ranged from 0 to 24.5 (4 patients asymptomatic, 3 with unspecific symptoms, and 13 with cerebellar signs). FDG-PET revealed hypometabolism in the asymptomatic stage in the vermis and right cerebellar hemisphere. In the ataxic stage, hypometabolism spread to both cerebellar hemispheres and the brain stem. MRI was normal in asymptomatic and preataxic individuals and showed superior cerebellar vermis atrophy early in the ataxic stage, diffuse cerebellar atrophy some years into the disease course, and a pattern of olivopontocerebellar atrophy in the oldest patients. There was no significant cerebellar atrophy in patients younger than 50 years. CONCLUSIONS: We present the first FDG-PET study of SCA36 and one of the largest neuroimaging study of SCAs. Our results revealed neuronal dysfunctions in the vermis and right cerebellar hemisphere as soon as a decade before the onset of motor symptoms. In the ataxic stage, dysfunctions spread to both hemispheres and the brain stem. © 2016 International Parkinson and Movement Disorder Society.

A method for estimating DMSA SPECT renal function for assessing the effect of percutaneous nephrolithotripsy on the treated pole.

BACKGROUND: The aim of this study was to develop a method for estimating DMSA SPECT renal function on each renal pole in order to evaluate the effect of percutaneous nephrolithotripsy by focusing the measurements on the region through which the percutaneous approach is performed. METHODS: Twenty patients undergoing percutaneous nephrolithotripsy between November 2010 and June 2012 were included in this study. Both Planar and SPECT-DMSA studies were carried out before and after nephrolithotripsy. The effect of percutaneous nephrolithotripsy was evaluated by estimating the total renal function and the regional renal function of each renal pole. Despite PCNL has been previously reported as a minimally invasive technique, our results showed regional renal function decreases in the treated pole in most patients, affecting the total renal function in a few of them. RESULTS: A quantification method was used for estimating the SPECT DMSA renal function of the upper, interpolar and lower renal poles. Our results confirmed that total renal function was preserved after nephrolithotripsy. Nevertheless, the proposed method showed that the regional renal function of the treated pole decreased in most patients (15 of 20 patients), allowing us to find differences in patients who had not shown changes in the total renal function obtained from conventional quantification methods. CONCLUSION: A method for estimating the SPECT DMSA renal function focused on the treated pole enabled us to show for the first time that nephrolithotripsy can lead to a renal parenchymal damage restricted to the treated pole.

Psoriasiform Eruption Secondary to the Use of Adalimumab.

Induced psoriasiform eruption, especially by anti-tumor necrosis factor alpha, was a rather rare event but nowadays cases are increasing because of its prescription for many different diseases. There are several clinical forms; one example is the pustulosis form presented in this case report.

Solid Lipid Nanoparticles: Multitasking Nano-Carriers for Cancer Treatment.

Despite all the advances seen in recent years, the severe adverse effects and low specificity of conventional chemotherapy are still challenging problems regarding cancer treatment. Nanotechnology has helped to address these questions, making important contributions in the oncological field. The use of nanoparticles has allowed the improvement of the therapeutic index of several conventional drugs and facilitates the tumoral accumulation and intracellular delivery of complex biomolecules, such as genetic material. Among the wide range of nanotechnology-based drug delivery systems (nanoDDS), solid lipid nanoparticles (SLNs) have emerged as promising systems for delivering different types of cargo. Their solid lipid core, at room and body temperature, provides SLNs with higher stability than other formulations. Moreover, SLNs offer other important features, namely the possibility to perform active targeting, sustained and controlled release, and multifunctional therapy. Furthermore, with the possibility to use biocompatible and physiologic materials and easy scale-up and low-cost production methods, SLNs meet the principal requirements of an ideal nanoDDS. The present work aims to summarize the main aspects related to SLNs, including composition, production methods, and administration routes, as well as to show the most recent studies about the use of SLNs for cancer treatment.

Intracellular Delivery of Anti-Kirsten Rat Sarcoma Antibodies Mediated by Polymeric Micelles Exerts Strong In Vitro and In Vivo Anti-Tumorigenic Activity in Kirsten Rat Sarcoma-Mutated Cancers.

The Kirsten rat sarcoma viral oncogene (KRAS) is one of the most well-known proto-oncogenes, frequently mutated in pancreatic and colorectal cancers, among others. We hypothesized that the intracellular delivery of anti-KRAS antibodies (KRAS-Ab) with biodegradable polymeric micelles (PM) would block the overactivation of the KRAS-associated cascades and revert the effect of its mutation. To this end, PM-containing KRAS-Ab (PM-KRAS) were obtained using Pluronic F127. The feasibility of using PM for antibody encapsulation as well as the conformational change of the polymer and its intermolecular interactions with the antibodies was studied, for the first time, using in silico modeling. In vitro, encapsulation of KRAS-Ab allowed their intracellular delivery in different pancreatic and colorectal cancer cell lines. Interestingly, PM-KRAS promoted a high proliferation impairment in regular cultures of KRAS-mutated HCT116 and MIA PaCa-2 cells, whereas the effect was neglectable in non-mutated or KRAS-independent HCT-8 and PANC-1 cancer cells, respectively. Additionally, PM-KRAS induced a remarkable inhibition of the colony formation ability in low-attachment conditions in KRAS-mutated cells. In vivo, when compared with the vehicle, the intravenous administration of PM-KRAS significantly reduced tumor volume growth in HCT116 subcutaneous tumor-bearing mice. Analysis of the KRAS-mediated cascade in cell cultures and tumor samples showed that the effect of PM-KRAS was mediated by a significant reduction of the ERK phosphorylation and a decrease in expression in the stemness-related genes. Altogether, these results unprecedently demonstrate that the delivery of KRAS-Ab mediated by PM can safely and effectively reduce the tumorigenicity and the stemness properties of KRAS-dependent cells, thus bringing up new possibilities to reach undruggable intracellular targets.

The Nanotechnology-Based Approaches against Kirsten Rat Sarcoma-Mutated Cancers.

Kirsten rat sarcoma (KRAS) is a small GTPase which acts as a molecular switch to regulate several cell biological processes including cell survival, proliferation, and differentiation. Alterations in KRAS have been found in 25% of all human cancers, with pancreatic cancer (90%), colorectal cancer (45%), and lung cancer (35%) being the types of cancer with the highest mutation rates. KRAS oncogenic mutations are not only responsible for malignant cell transformation and tumor development but also related to poor prognosis, low survival rate, and resistance to chemotherapy. Although different strategies have been developed to specifically target this oncoprotein over the last few decades, almost all of them have failed, relying on the current therapeutic solutions to target proteins involved in the KRAS pathway using chemical or gene therapy. Nanomedicine can certainly bring a solution for the lack of specificity and effectiveness of anti-KRAS therapy. Therefore, nanoparticles of different natures are being developed to improve the therapeutic index of drugs, genetic material, and/or biomolecules and to allow their delivery specifically into the cells of interest. The present work aims to summarize the most recent advances related to the use of nanotechnology for the development of new therapeutic strategies against KRAS-mutated cancers.

Familial hemiplegic migraine with prolonged global aura: follow-up findings of subtraction ictal SPECT co-registered to MRI (SISCOM).

All authors contributed equally to this work. Susana Arias-Rivas wrote the main paper. Manuel Rodriguez-Yáñez investigated the supplementary data. Julia Cortés and Pablo Aguiar performed the nuclear image studies and analysed and described the neuroimaging results. María Pardo, Rogelio Leira and Jose Castillo jointly conceived the study, followed the patient and prepared the manuscript. Miguel Blanco discussed the results. All authors discussed the results and implications and commented on the manuscript at all stages.

Arsenic removal from groundwater of the Chaco-Pampean plain (Argentina) using natural geological materials as adsorbents.

Use of natural geological materials for arsenic (As) removal is an emerging solution at a household level for poor people in remote rural settlements, especially when the materials are locally available and can be collected by the local population. Their low or zero cost makes these materials very attractive compared with synthetic or commercial materials. Sometimes, this may be the only option to provide safe water to very poor settlements. Their suitability for As removal from water is mainly due to adsorption, co-precipitation and ion exchange processes involving Fe- and Al-rich minerals and clay minerals present in the soils or sediments. In the present study, various clay-rich soils from the Santiago del Estero province (SDE, NW Argentina) and, for comparison, a laterite from the Misiones province have been tested as adsorbents for As in shallow naturally contaminated groundwaters of the Río Dulce alluvial aquifer in SDE. Batch adsorption experiments showed higher As(V) removal for the Misiones laterite sample (99 %) as compared with the soils from SDE (40-53 %), which can be related to lower contents of water-soluble and oxalate extractable Al and Fe in the last samples. These results suggest the application of the Misiones laterite soil as an alternative for As removal. However, high transportation costs from Misiones to SDE can be an economical restriction for the low-income population of SDE.

Staging the cognitive continuum in prodromal Alzheimer's disease with episodic memory.

It is unclear whether episodic memory is an appropriate descriptor of the cognitive continuum in mild cognitive impairment (MCI). Here, we investigated the ability of episodic memory to track cognitive changes in patients with MCI with biomarker evidence of Alzheimer's disease (AD). We examined 387 MCI amyloid-positive subjects, cognitively staged as "early" or "late" on the basis of episodic memory impairment. Cross-sectional and longitudinal comparisons between these 2 groups were performed for each amyloid, tau, and neurodegeneration (AT(N)) profile. Cross-sectional analyses indicate that "early" MCI represents a transitional phase between normal cognition and "late" MCI in the AD biomarker pathway. After adjusting by confounders and levels of A, T, and (N), "late" MCI progressed significantly faster than "early" MCI only in profiles with both abnormal amyloid and tau markers (A+T+(N)- p < 0.05, A+T+(N)+ p < 0.001). Episodic memory staging is useful for describing symptoms in prodromal AD and complements the AT(N) profiles. Our findings might have implications for the Numeric Clinical staging scheme of the National Institute on Aging and Alzheimer's Association research framework.

Prediction of Alzheimer's disease dementia with MRI beyond the short-term: Implications for the design of predictive models.

Magnetic resonance imaging (MRI) volumetric measures have become a standard tool for the detection of incipient Alzheimer's Disease (AD) dementia in mild cognitive impairment (MCI). Focused on providing an earlier and more accurate diagnosis, sophisticated MRI machine learning algorithms have been developed over the recent years, most of them learning their non-disease patterns from MCI that remained stable over 2-3 years. In this work, we analyzed whether these stable MCI over short-term periods are actually appropriate training examples of non-disease patterns. To this aim, we compared the diagnosis of MCI patients at 2 and 5 years of follow-up and investigated its impact on the predictive performance of baseline volumetric MRI measures primarily involved in AD, i.e., hippocampal and entorhinal cortex volumes. Predictive power was evaluated in terms of the area under the ROC curve (AUC), sensitivity, and specificity in a trial sample of 248 MCI patients followed-up over 5 years. We further compared the sensitivity in those MCI that converted before 2 years and those that converted after 2 years. Our results indicate that 23% of the stable MCI at 2 years progressed in the next three years and that MRI volumetric measures are good predictors of conversion to AD dementia even at the mid-term, showing a better specificity and AUC as follow-up time increases. The combination of hippocampus and entorhinal cortex yielded an AUC that was significantly higher for the 5-year follow-up (AUC = 73% at 2 years vs. AUC = 84% at 5 years), as well as for specificity (56% vs. 71%). Sensitivity showed a non-significant slight decrease (81% vs. 78%). Remarkably, the performance of this model was comparable to machine learning models at the same follow-up times. MRI correctly identified most of the patients that converted after 2 years (with sensitivity >60%), and these patients showed a similar degree of abnormalities to those that converted before 2 years. This implies that most of the MCI patients that remained stable over short periods and subsequently progressed to AD dementia had evident atrophies at baseline. Therefore, machine learning models that use these patients to learn non-disease patterns are including an important fraction of patients with evident pathological changes related to the disease, something that might result in reduced performance and lack of biological interpretability.

Cardiac function after CPAP therapy in patients with chronic heart failure and sleep apnea: a multicenter study.

BACKGROUND AND PURPOSE: Continuous positive airway pressure (CPAP) is an effective treatment for sleep apnea (SA), although the evidence for improving chronic heart failure (CHF) is inconclusive. Our aim was to evaluate the effect of CPAP treatment on the left ventricle ejection fraction (LVEF) among other cardiological variables in a randomized, multicenter, placebo (sham-CPAP)-controlled study. METHODS: After the selection procedure, 60 patients with CHF with LVEF<45% and SA with an apnea-hypopnea index (AHI)>10/h were evaluated at baseline, and after 3 months of treatment with optimal CPAP or sham-CPAP. The assessment was based on the LVEF, hypertension, daytime sleepiness (Epworth sleepiness scale [ESS]), quality of life (SF-36), New York Heart Scale (NYHA score), dyspnea (by using the Borg scale) and exercise tolerance (6-min walk test). RESULTS: The mean AHI was normalized in the optimal CPAP group but not in the sham-CPAP group. The LVEF showed a significant improvement in the group of patients treated with CPAP (2.5; 95% CI: 0.6 to 4.3), which was not observed in the sham-CPAP group (0.0; 95% CI: -2.1 to 2.1). However, the change in the LVEF from baseline to 3 months was not significantly greater in the whole group (obstructive and Cheyne-Stokes events) treated with CPAP than in the control group (p: 0.07). In patients with only obstructive sleep apnea (OSA), who account for 83% of the total population, there was a significant improvement in the LVEF in the group of patients treated with CPAP but no such improvement in the sham-CPAP group. In this OSA group, the change in the LVEF from baseline to 3 months was significantly greater in the group treated with CPAP than in the sham-CPAP group (p: 0.03). The other variables studied were not modified. When the patients were divided according to the severity of the LVEF (a LVEF cut-off of 30%), improvement was observed in those with a LVEF>30. No changes were found in the other cardiological variables. CONCLUSIONS: CPAP therapy proved to be useful in patients with associated sleep-disordered breathing and CHF. The improvement was more marked in patients with a LVEF>30%. However, the increased LVEF in the CPAP group was not accompanied by changes in the other cardiological variables.

Regulación de la respuesta inflamatoria dependiente de citocinas / Regulation of the inflammatory response dependent on cytokines i: en

Las citocinas son hormonas proteicas que permiten la comunicación intercelular, estimulan la activación de receptores de membrana específicos, poseen funciones de diferenciación celular y proliferación, participan en la quimiotaxis, así como en el crecimiento y la modulación de la secreción de inmunoglobulinas; no obstante, su acción principal está dada por la regulación del mecanismo de la inflamación. Las principales citocinas encargadas de esto son las interleucinas 1, 8, 12 y 16; además del factor de necrosis tumoral alfa e interferones, todas ellas proinflamatorias. Las interleucinas 6 y 12 también actúan en la inmunidad específica.

Cytokines are protein hormones that allow the intercellular communication, stimulate the activation of specific membrane receptors, have cell differentiation functions and proliferation, participate in the chemotaxis, as well as in the growth and modulation of immunoglobulin secretion; nevertheless, their main action is given by the regulation of the inflammation mechanism. The main cytokines in charge of this are interleukins 1, 8, 12 and 16, besides the tumor necrosis factor alpha and interferons, all of them proinflammatory. Interleukins 6 and 12 also act in the specific immunity.

Avaliação do perfil epidemiológico das hepatites virais no Brasil - 2010 A 2021 / Evaluation of the epidemiological profile of viral hepatitis in Brazil - 2010 to 2021

As hepatites virais são doenças que apresentam elevado impacto de morbimortalidade no mundo, sendo assim, consideradas um grave problema para a saúde pública. Nos últimos anos o enfrentamento das hepatites virais tem sido um grande desafio, principalmente para os países com alta prevalência de vulnerabilidades sociais. Medidas de controle e prevenção da doença devem ser tomadas, por isso torna-se necessário a realização de estudos que contemplem conhecimentos sobre a dinâmica epidemiológica das hepatites para demonstrar sua importância em relação a saúde pública. Objetivo: O objetivo nesta pesquisa foi analisar o perfil epidemiológico das hepatites virais no Brasil, no período de 2010 a 2021. Método: Realizou-se um estudo transversal, descritivo, retrospectivo e qualiquantitativo que utilizou como unidades de análise as unidades federativas brasileiras. Os dados foram coletados a partir das informações disponíveis no site TABNET/DATASUS, DCCI, e a estimativa da população anual absoluta foi obtida no Instituto Brasileiro de Geografia e Estatística (IBGE). Resultados: No período analisado foram registrados 476.981 casos de hepatites virais no Brasil, destacando-se a notificação de casos de hepatite C, seguida pela hepatite B, A e D. Com relação a taxa de incidência, a Região Norte destacou-se para hepatite A e D, e a Região Sudeste para hepatite B e C. O sexo do indivíduo acometido em todos os tipos de hepatite virais analisados que se destacou foi o masculino, mas com pouca diferença do feminino. Foram registrados 25.553 óbitos, sendo 78,3% devido à hepatite C. A presente pesquisa nos permitiu concluir que o tipo de hepatite mais relatada no Brasil é a tipo C, assim como a que mais provoca óbitos. Todas as hepatites virais apresentaram queda nas notificações no ano de 2020 e 2021 e por isso este fato deve ser analisado pelos setores de vigilância pois pode se tratar de subnotificações, principalmente devido a situação do país neste período, que enfrentava a pandemia de COVID-19

Viral hepatitis is a disease with a high impact on morbidity and mortality worldwide and hence considered a serious problem for public health. Fighting viral hepatitis has been a major challenge in recent years, especially for countries with a high prevalence of social vulnerabilities. Measures to control and prevent the disease must therefore be taken, so studies that include knowledge about the epidemiological dynamics of hepatitis are warranted to demonstrate its importance to public health. In the objective of the present study was to analyze the epidemiological profile of viral hepatitis in Brazil in the period from 2010 to 2021. A cross-sectional, descriptive, retrospective, and qualitative-quantitative investigation was carried out using the federative units of Brazil as units of analysis. Data were collected from information available on the TABNET/DATASUS, DCCI website, and the absolute annual population estimate was obtained from the Brazilian Institute of Geography and Statistics (IBGE). In the analyzed period, 476,981 cases of viral hepatitis were recorded in Brazil, the majority of which referred to hepatitis C, followed by hepatitis B, A, and D. As regards the incidence rate, the north region stood out with hepatitis A and D; and the southeast region with hepatitis B and C. Males prevailed between the genders of individuals affected, considering all types of viral hepatitis analyzed, but with little difference from females. A total of 25,553 deaths were recorded, 78.3% of which were due to hepatitis C. Conclusions: The present study allowed us to conclude that the most reported type of hepatitis in Brazil is type C, which is also the most death-causing. There was a drop in notifications of all viral hepatitis in 2020 and 2021, and this fact should be analyzed by surveillance sectors as it may be a situation of underreporting, due mainly to the COVID-19 pandemic crisis the country was facing in the period

Sarcoid-like cutaneous lesions in chronic adult paracoccidioidomycosis: report of two cases.

This study reports two cases of chronic paracoccidioidomycosis with sarcoid-like cutaneous lesions. The patients began the treatment in 2013 at Hospital Universitário Clementino Fraga Filho (HUCFF) of the Universidade Federal do Rio de Janeiro (UFRJ). The first case (mild form) was treated with trimethoprim-sulfamethoxazole (8 mg /kg per day, orally) for three months and, then, with half the dose for nine months; the second (moderate form), with itraconazole (200 mg per day, orally) for 12 months. We point out the rareness of the sarcoid-like cutaneous lesions and the differential diagnoses for other granulomatous diseases.

In vivo eye surface residence determination by high-resolution scintigraphy of a novel ion-sensitive hydrogel based on gellan gum and kappa-carrageenan.

In last years, sensitive hydrogels have become a breakthrough in ophthalmic pharmaceutical technology aimed at developing new strategies to increase the residence time of active substances. In a previous paper, we qualitatively demonstrated the capacity of a new ion sensitive hydrogel to increase the residence time. Nevertheless, the clearance of the gel from the ocular surface was not quantifiable with the used methodology. The aim of the present work was to use a well-established approach based on scintigraphy to quantitatively estimate the residence time of the previously proposed hydrogel. The rat corneal residence time of a topic ophthalmic formulation containing gellan gum and kappa carragenan (0.82% w/v) labeled with 99mTc-DTPA radiotracer was evaluated and compared with the residence of an aqueous solution. Ophthalmic safety studies such as eye irritation or passage through the cornea were also carried out. After 1.5h of contact, 77% of the hydrogel remained in the ocular surface, presenting kinetics of disappearance one-phase decay and a half time of 262min. We conclude that the novel ophthalmic hydrogel developed with kappa carrageenan and gellan gum remains for long periods of time on the corneal surface, presenting a drop that fits an exponential decay.

Role of sonography in the diagnosis of axillary lymph node metastases in breast cancer: a systematic review.

OBJECTIVE: The purpose of our study was to evaluate the accuracy of sonography and sonographically guided biopsy in the preoperative diagnosis of metastatic invasion of the axilla in patients with breast carcinoma. MATERIALS AND METHODS: We performed a MEDLINE search (keywords, "sonography" OR "ultrasound" AND "axillary") and a manual search of the references of relevant studies and reviews of preoperative diagnosis on sonography of possible axillary metastases. The gold standard required was axillary lymph node dissection; we accepted sentinel node biopsy as an alternative gold standard. Considering the sonographic findings and the results of the sonographically guided biopsy, the sensitivity and specificity were calculated using metaanalysis. We also checked the existence of heterogeneity of the summary results. RESULTS: Sixteen articles were selected. In sonography of axillae without palpable nodes, and using lymph node size as the criterion for positivity, sensitivity varied between 48.8% (95% confidence interval, 39.6-58%) and 87.1% (76.1-94.3%) and specificity, between 55.6% (44.7-66.3%) and 97.3% (86.1-99.9%). When lymph node morphology was used as the criterion for positivity, sensitivity ranged from 26.4% (15.3-40.3%) to 75.9% (56.4-89.7%) and specificity, from 88.4% (82.1-93.1%) to 98.1% (90.1-99.9%). The results are different if axillae with palpable nodes are included. The sonographically guided biopsy shows a sensitivity that varies between 30.6% (22.5-39.6%) and 62.9% (49.7-74.8%) and a specificity of 100% (94.8-100%). Many of the summary results obtained after meta-analysis show a heterogeneity that disappears, on occasion, on excluding the studies that use a double gold standard. CONCLUSION: Axillary sonography is moderately sensitive and fairly specific in the diagnosis of axillary metastatic involvement. Sonographically guided biopsy of the sonographically suspicious nodes somewhat increases the specificity, which reaches 100%. Negative sonographic results do not exclude axillary lymph node metastases.

Estimación del riesgo cardiovascular en adultos mayores con hipertensión arterial / Estimate of the cardiovascular risk in the elderly with hypertension

Introducción: La necesidad de disminuir la morbilidad y la mortalidad por enfermedades cardiovasculares y cerebrovasculares ha sido el principal motivo para enfocar el problema del control de la hipertensión arterial desde un punto de vista más integral. Objetivo: Estimar el riesgo cardiovascular en adultos mayores con hipertensión arterial atendidos en un área de salud. Métodos: Se realizó un estudio descriptivo y trasversal de 103 adultos mayores con hipertensión arterial, pertenecientes al Consultorio Médico de la Familia No. 23 del Policlínico Docente Ramón López Peña de Santiago de Cuba, desde enero hasta diciembre del 2019. Se estudiaron variables sociodemográficas (edad, sexo, color de la piel) y clínicas (clasificación y control de la enfermedad); además, se estimó el riesgo cardiovascular según la Guía cubana de diagnóstico, evaluación y tratamiento de la hipertensión arterial. Se utilizaron técnicas de la estadística descriptiva, tales como frecuencia absoluta y porcentaje, así como medidas de tendencia central. Resultados: Predominaron las mujeres, fundamentalmente de edades más avanzadas, y las personas con piel negra. Los factores de riesgo más frecuentes fueron alimentación deficiente, sedentarismo y diabetes mellitus. El riesgo cardiovascular moderado primó en 56,0 % de la población. Conclusiones: Los pacientes estudiados mostraron un riesgo de moderado a alto de presentar eventos cardiovasculares en los próximos años, elemento básico para la planificación e implementación de acciones preventivas y de control que, sin lugar a dudas, redundará en una disminución de la morbilidad y la mortalidad por enfermedades cardiovasculares y cerebrovasculares.

Introduction: The necessity to diminish the morbidity and mortality due to cardiovascular and cerebrovascular diseases has been the main reason to focus the problem of hypertension control from a more comprehensive point of view. Objective: To estimate the cardiovascular risk in the elderly with hypertension assisted in a health area. Methods: A descriptive and cross-sectional study of 103 elderly with hypertension, belonging to the Doctor Family Office No. 23 of Ramón López Peña Teaching Polyclinic was carried out in Santiago de Cuba, from January to December, 2019. Some sociodemographic and clinical variables were studied (age, sex, color of the skin) and (classification and control of the disease) respectively; also, the cardiovascular risk was considered according to the Cuban guide of diagnosis, evaluation and treatment of hypertension. The techniques of the descriptive statistic were used, such as absolute frequency and percentage, as well as measures of central tendency. Results: There was a prevalence of women, fundamentally of more advanced ages, and people with black skin. The most frequent risk factors were poor feeding, physical inactivity and diabetes mellitus. The moderate cardiovascular risk prevailed in the 56.0 % of the population. Conclusions: The studied patients showed a moderate to high risk for presenting cardiovascular events in the next years, basic element for planning and implementing preventive and control actions that, undoubtedly, will rebound in a decrease of morbidity and mortality due to cardiovascular and cerebrovascular diseases.