Long-term surveillance of the feline leukemia virus in the endangered Iberian lynx (Lynx pardinus) in Andalusia, Spain (2008-2021).

Feline leukemia virus (FeLV) infection is considered one of the most serious disease threats for the endangered Iberian lynx (Lynx pardinus) Over 14 years (2008-2021), we investigated FeLV infection using point-of-care antigen test and quantitative real-time TaqMan qPCR for provirus detection in blood and tissues in lynxes from Andalusia (Southern Spain). A total of 776 samples from 586 individuals were included in this study. The overall prevalence for FeLV antigen in blood/serum samples was 1.4% (5/360) (95% CI: 0.2-2.6), FeLV proviral DNA prevalence in blood samples was 6.2% (31/503) (95% CI: 4.1-8.6), and FeLV proviral DNA in tissues samples was 10.2% (34/333) (95% CI: 7-13.5). From a subset of 129 longitudinally sampled individuals, 9.3% (12/129) PCR-converted during the study period. Our results suggest that FeLV infection in the Andalusian population is enzootic, with circulation of the virus at low levels in almost all the sampling years. Moreover, since only one viremic individual succumbed to the infection, this study suggests that lynxes may therefore control the infection decreasing the possibility of developing a more aggressive outcome. Although our results indicate that the FeLV infection in the Iberian lynx from Andalusia tends to stay within the regressive stage, continuous FeLV surveillance is paramount to predict potential outbreaks and ensure the survival of this population.

High Rate of Inappropriate Antibiotics in Patients with Hematologic Malignancies and Pseudomonas aeruginosa Bacteremia following International Guideline Recommendations.

Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to detail current rates of resistance to antibiotics recommended by international guidelines for P. aeruginosa isolated from bloodstream infections (BSI) in patients with hematologic malignancies. Secondarily, we aimed to describe how many patients received inappropriate empirical antibiotic treatment (IEAT) and its impact on mortality. We conducted a retrospective, multicenter cohort study of the last 20 BSI episodes caused by P. aeruginosa in patients with hematologic malignancies from across 14 university hospitals in Spain. Of the 280 patients with hematologic malignancies and BSI caused by P. aeruginosa, 101 (36%) had strains resistant to at least one of the ß-lactam antibiotics recommended in international guidelines, namely, cefepime, piperacillin-tazobactam, and meropenem. Additionally, 21.1% and 11.4% of the strains met criteria for MDR and XDR P. aeruginosa, respectively. Even if international guidelines were followed in most cases, 47 (16.8%) patients received IEAT and 66 (23.6%) received inappropriate ß-lactam empirical antibiotic treatment. Thirty-day mortality was 27.1%. In the multivariate analysis, pulmonary source (OR 2.22, 95% CI 1.14 to 4.34) and IEAT (OR 2.67, 95% CI 1.37 to 5.23) were factors independently associated with increased mortality. We concluded that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines, which is associated with frequent IEAT and higher mortality. New therapeutic strategies are needed. IMPORTANCE Bloodstream infection (BSI) caused by P. aeruginosa is related with an elevated morbidity and mortality in neutropenic patients. For this reason, optimal antipseudomonal coverage has been the basis of all historical recommendations in the empirical treatment of febrile neutropenia. However, in recent years the emergence of multiple types of antibiotic resistances has posed a challenge in treating infections caused by this microorganism. In our study we postulated that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines. This observation is associated with frequent IEAT and increased mortality. Consequently, there is a need for a new therapeutic strategy.

BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging.

Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson's disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson's disease. In these patients and in one monkey, blood-brain barrier opening was followed by 18F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders.

Standard deviations of MR signal intensities show a consistent trend during imaging follow-ups for glioblastoma patients when corrected for non-biological heterogeneity due to hardware and software variation.

INTRODUCTION: Glioblastoma multiforme (GBM) has a poor prognosis in spite of advanced MRI guided treatments today. Routine MRI using conventional T1 or advanced permeability based MRI of GBM often does not adequately represent changing tumor phases or overall survival. In this work, region of interest (ROI) based tissue MR standard deviation (SD) is demonstrated as an important MRI variable that could be a potential biomarker of GBM heterogeneity and radioresistance. MATERIALS AND METHODS: MRI characterization is often qualitative and lacks reproducibility. Using standardized MRI phantoms we have normalized retrospective records of 12 radioresistant GBM patients that underwent radiation therapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy followed by serial MR imaging with gadolinium contrast. RESULTS AND DISCUSSION: We have identified key variables like hardware, software and protocol variation and have standardized those using test phantoms at five MR systems. We suggest GBM growth during the treatment period can be linked to normalized MRI signal and its fluctuations from session to session and from magnet to magnet by using an ROI derived standard deviation that corresponds to heterogeneity of the tumor MRI signal and changes in magnetic susceptibility. The time period observed in our patient group for peak standard deviations is approximately halfway through the tumor course and may correspond to a growth of more aggressive MES subtype of cells. To model the GBM heterogeneity we performed in vitro T1 weighted inversion recovery MRI experiments at 3 T for porous media of silicate particles in 1% aq solution of Gadavist and linked SD with particle size and local gadolinium volume within porous media. Such in vitro models mimic the increased SD in radioresistant GBM and as a novel contribution suggest that finer texture with high surface area might arise approximately halfway through the overall survival duration in GBM. CONCLUSION: Standard deviation as a measure of magnetic susceptibility may be collectively linked to the changes in texture, cell fractions (biological) and trapped contrast media (vascular as well as artifactual consequences) and should be evaluated as a potential biomarker of GBM aggressiveness than the overall MRI signal intensity from a GBM.

Humoral/Cellular Immune Discordance in Stem Cell Donors: Impact on Cytomegalovirus-Specific Immune Reconstitution after Related Hematopoietic Transplantation.

Cytomegalovirus (CMV) reactivation is an important cause of complications after hematopoietic stem cell transplantation (HSCT). Discrepancies between serologic and cellular CMV-specific immune response have been reported. This study evaluated the impact of lack of CMV-specific CD8+ T cell response in seropositive donors (ie, discordant donors) on the reconstitution of CMV-specific cell-mediated immunity (CMI) after related HSCT in seropositive recipients. CMV-CMI was assessed in donors and recipients using the QuantiFERON-CMV assay (QF). CMV-CMI was prospectively assessed for 1 year in 81 CMV-seropositive HSCT recipients with a haploidentical or matched related donor. A Cox proportional hazard regression analysis was performed. Of the 67 CMV-seropositive donors, 54 (80.6%) were D+QFpos. The remaining 13 CMV-seropositive donors (19.4%) had a QFneg result and thus were classified as discordant donors (D+QFneg). We found that patients with D+QFneg had a significantly higher risk of impaired CMV-CMI reconstitution compared with patients with D+QFpos (log-rank test, P = .001) or D- donors (log-rank test, P = .023). In addition, the D+QFneg group had a higher incidence of single-episode reactivation compared with D+QFpos or D- donors (69.2% versus 44.4% and 28.6%, respectively) but a lower incidence of CMV recurrence compared with the D- group (7.7% versus 57.1%; P = .003). After adjusting for other relevant variables, immune discordance in donors was independently associated with impaired CMV-CMI reconstitution compared with D+QFpos donors (adjusted hazard ratio [HR], 0.18; 95% confidence interval [CI], .06 to .52; P = .001) and D- donors (adjusted HR, .17; 95% CI, .05 to .59; P = .005). Discordant donors were associated with undetectable CMV-CMI during the 12-month follow-up period using the QF assay. The inability of these patients to become QFpos persisted even after CMV reactivation. This might be related to the low frequency of CMV recurrence in this group. CMV-CMI assessment, in conjunction with CMV serostatus, can be of utility to better classify stem cell donors as well as the risk of impaired CMV-CMI reconstitution after HSCT.

Lesion 3D modeling in transcranial MR-guided focused ultrasound thalamotomy.

Transcranial magnetic resonance-guided focused ultrasound (tMRgFUS) allows to perform incisionless thermoablation of deep brain structures. This feature makes it a very useful tool for the treatment of multiple neurological and psychiatric disorders. Currently, feedback of the thermoablation process is based on peak temperature readings assessed on real-time two-dimensional MRI thermometry. However, an accurate methodology relating thermal dosimetry with three-dimensional topography and temporal evolution of the lesion is still to be defined, thus hurdling the establishment of well-defined, evidence-based criteria to perform safe and effective treatments. In here we propose threshold-based thermoablation models to predict the volumetric topography of the lesion (whole lesion and necrotic core) in the short-to-mid-term based on thermal dosimetry estimated from intra-treatment MRI thermometry. To define and validate our models we retrospectively analyzed the data of sixty-three tMRgFUS thalamotomies for treating tremor. We used intra-treatment MRI thermometry to estimate whole-treatment three-dimensional thermal dose maps, defined either as peak temperature reached (Tmax) or thermal isoeffective dose (TID). Those maps were thresholded to find the dosimetric level that maximize the agreement (Sorensen-Dice coefficient - SDc) with the boundaries of the whole lesion and its core, assessed on T2w images 1-day (post-24h) and 3-months (post-3M) after treatment. Best predictions were achieved for the whole lesion at post-24h (SDc = 0.71), with Tmax /TID over 50.0 °C/90.5 CEM43. The core at post-24h and whole lesion at post-3M lesions reported a similar behavior in terms of shape accuracy (SDc ~0.35), and thermal dose thresholds ~55 °C/4100.0 CEM43. Finally, the optimal levels for post-3M core lesions were 55.5 °C/5800.0 CEM43 (SDc = 0.21). These thermoablation models could contribute to the real-time decision-making process and improve the outcome of tMRgFUS interventions both in terms of safety and efficacy.

Covid 19: Eating behavior changes related to individual and household factors during the COVID-19 lockdown in Spain

To analyze the influence of individual and household factors on eating behavior (EB) and other determinants related to eating during the home lockdown in the Covid-19 pandemic. Method: Online survey (April 17 to May 10, 2020) to collect sociodemographic information, health, and various EB attitudes. Statistical analysis of the factors: country, setting, sex, BMI classification, lockdown period, a household with children under 15 years, nutritional needs, age groups, type and size household, monthly income, and religion. Results: 1055 households participated. 75% have modified their eating habits, with differences due to being overweight or obese in the person surveyed (p <0.05). Changes in EB and other lifestyles are influenced by household structure (p <0.001) and the effects that the pandemic has had on the economy of families (p <0.001). Compared to those who do not have them, households with children tend to plan much more meals, spend more time eating, seek a healthier diet, increase the number of daily meals, and look more at labeling. In contrast, people who live alone have worsened the hourly routines of the main meals. Conclusions: Confinement has modified eating behavior differently depending on the individual and domestic factors analyzed(AU)

Analizar la influencia de factores individuales y del hogar sobre el comportamiento alimentario (CA), y otros determinantes relacionados con la alimentación, durante el confinamiento domiciliario en la pandemia por Covid-19. Método: Encuesta online (17 abril al 10 de mayo de 2020) para recopilar información sociodemográfica, de salud y diversas actitudes del CA. Análisis estadístico sobre los factores: país, ámbito, sexo, IMC, tiempo de confinamiento, hogar con menores de 15 años, necesidades nutricionales, grupos de edad, tipo y tamaño del hogar, ingresos y religión. Resultados: Participaron 1055 hogares. El 75% ha modificado sus hábitos alimentarios, con diferencias por sobrepeso u obesidad de la persona encuestada (p<0.05). Los cambios en el CA y otros estilos de vida están influenciados por la estructura del hogar (p<0.001) y los efectos que la pandemia ha tenido sobre la economía de las familias (p<0.001). Los hogares que tienen hijos/as, respecto a los que no los tienen, tienden a planificar mucho más las comidas, dedicar más tiempo a la alimentación, procuran una alimentación más saludable, incrementan el número de comidas diarias y miran más el etiquetado. Por el contrario, las personas que viven solas han empeorado las rutinas horarias de las principales comidas. Conclusiones: El confinamiento ha modificado de manera diferenciada el comportamiento alimentario en función de los factores individuales y domésticos analizados(AU)

Changes in the Organosulfur and Polyphenol Compound Profiles of Black and Fresh Onion during Simulated Gastrointestinal Digestion.

This study aims to determine the changes in, and bioaccessibility of, polyphenols and organosulfur compounds (OSCs) during the simulated gastrointestinal digestion of black onion, a novel product derived from fresh onion by a combination of heat and humidity treatment, and to compare it with its fresh counterpart. Fresh and black onions were subjected to in-vitro gastrointestinal digestion, and their polyphenol and OSC profiles were determined by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Although to a lesser extent than in the fresh onion, the phenolic compounds in the black variety remained stable during the digestion process, presenting a higher bioaccessibility index (BI) with recovery corresponding to 41.1%, compared with that of fresh onion (23.5%). As for OSCs, apart from being more stable after the digestion process, with a BI of 83%, significantly higher quantities (21 times higher) were found in black onion than in fresh onion, suggesting that the black onion production process has a positive effect on the OSC content. Gallic acid, quercetin, isorhamnetin, and ɣ-glutamyl-S-(1-propenyl)-L-cysteine sulfoxide were the most bioaccessible compounds in fresh onion, while isorhamnetin, quercetin-diglucoside, ɣ-glutamyl-S-methyl-L-cysteine sulfoxide and methionine sulfoxide were found in black onion. These results indicate that OSCs and polyphenols are more bioaccessible in black onion than in fresh onion, indicating a positive effect of the processing treatment.

Blood-brain barrier opening with focused ultrasound in Parkinson's disease dementia.

MR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson's disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in ß-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2-3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.

Neglected and (re-)emergent infections of the CNS i n low-/middle-income countries.

Low- and middle-income countries (LMIC) have suffered from long-term health system deficiencies, worsened by poor living conditions, lack of sanitation, a restricted access to health facilities and running water, overcrowding, and overpopulation. These factors favor human displacement and deepen marginalization; consequently, their population endures a high burden of infectious diseases. In this context, the current epidemiological landscape and its impact on health and economic development are not promissory, despite the commitment by the international community to eradicate neglected tropical infections - especially tuberculosis and malaria, by 2030. Neglected and (re)-emerging infectious diseases affecting the central nervous system (CNS) are a major public health concern in these countries, as they cause a great morbidity and mortality; furthermore, survivors often suffer from severe neurological disabilities. Herein, we present a retrospective review focused on some neglected and (re)-emerging infectious diseases, including neurocysticercosis, malaria, rabies, West Nile virus encephalitis, tuberculosis, neuroborreliosis, and SARS-CoV-2 in LMIC. A retrospective review of studies on selected neglected and (re)-emerging infectious diseases in LMIC was performed, including reports by the World Health Organization (WHO) published within the last five years. Data on infection by SARS-CoV-2 were provided by the John Hopkins University Coronavirus Resource Center. CNS neglected and (re)-emerging infectious diseases remain as important causes of disease in LMIC. An alarming increase in the prevalence of malaria, tuberculosis, and cysticercosis is observed in the region, compounded by the recent COVID-19 pandemic. The WHO is currently supporting programs/efforts to cope with these diseases. Herein, we highlight the epidemiological burden of some CNS infections in LMIC, and their clinical and neuroimaging features, to facilitate an accurate diagnosis, considering that most of these diseases will not be eradicated in the short term; instead, their incidence will likely increase along with poverty, inequality, and related socioeconomic problems.

Long-term refractive outcomes in patients with cataracts and keratoconus after phacoemulsification with toric intraocular lens implant.

PURPOSE: To determine the refractive stability of patients with keratoconus and cataracts after the implantation of a toric intraocular lens. METHODS: This is a cross-sectional, retrospectivestudy. Clinical records from patients with non-progressive keratoconus and cataracts that underwent non-complicated phacoemulsification with toric IOL implantation were reviewed. Mean keratometry (Km), refractive cylinder (RC), spherical equivalent (SE), steeper keratometry (K), and axis were evaluated at the 1-month, 6-month, 12-month, and 24-month follow-up visits. RESULTS: Fifty-four eyes from 41 patients were included. Thirty-seven (68.5%) female and 17 (31.5%) male patients, with a mean age of 67.52 ± 8.22. Refractive cylinder at postoperative 30 days was -1.61 ± 1.23, 6-month -1.22 ± 0.80, 12-month -1.10 ± 0.83 and 24-month visit after surgery was -1.37 ± 0.77(p = 0.290). SE at the 30-day visit was -0.82 ± 1.90, 6-month -0.64 ± 1.23, 12-month -0.78 ± 1.91 and at 24-month postoperative visit -1.02 ± 1.87 (p = 0.210). Km value at the 1-month visit was 47.23 ± 1.95, 6-month 47.87 ± 1.61, 12-month 46.39 ± 2.52 and 24-month postoperative visit 46.92 ± 1.26 (p = 0.877). The steeper K axis in the 30-day control was 78.53 ± 30.12, 6-month 77.29± 37.68, 1-year 93.13 ± 62.42, 24-month 67.31 ± 38.49 (p = 0.632). CONCLUSIONS: Our findings suggest a low variation in the refractive outcome for patients with mild and moderate keratoconus and cataracts, without evident progression signals, a demonstrated keratoconus clinical stability. No statistically significant postoperative changes in the refractive cylinder, SE, mean K, and steeper K axis were observed, which suggests good predictability for toric IOL implant.

Relationship between pineal cyst size and aqueductal CSF flow measured by phase contrast MRI.

BACKGROUND: Most patients with pineal cysts referred for neurosurgical consultation have no specific symptoms or objective findings except for pineal cyst size to help in management decisions. Our purpose was to assess the relationship between pineal cyst size and aqueductal CSF flow using PC-MRI. METHODS: Eleven adult patients with pineal cysts (>1 cm) referred for neurosurgical consultations were included. Cyst volume was calculated using 3D T1 images. Phase contrast magnetic resonance imaging (PC-MRI) in axial plane with velocity encoding of 5 cm/sec was used to quantitatively assess CSF flow through the cerebral aqueduct to determine the aqueductal stroke volume, which was then correlated to cyst size using Pearson's correlation. Pineal cysts were grouped by size into small (6/11) and large (5/11) using the median value to compare aqueductal stroke volume using Mann-Whitney test. RESULTS: Patients were 39±13 years (mean±SD) of age, and 10/11 (91%) were female. There was significant negative correlation between cyst volume and aqueductal stroke volume (r=0.74; P=0.009). Volume of small cysts (4954±2157 mm3) was significantly different compared to large cysts (13,752±3738 mm3; P=0.008). The aqueductal stroke volume of patients harboring large cysts 33±8 µL/cardiac cycle was significantly lower than that of patients with small cysts 96±29 µL/cardiac cycle (P=0.008). CONCLUSIONS: Aqueductal CSF flow appears to decrease with increasing pineal cyst size. Our preliminary results provide first evidence that even in the absence of objective neurological findings or hydrocephalus; larger pineal cysts already display decreased CSF flow through the cerebral aqueduct.

Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson's Disease.

BACKGROUND: The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus. METHODS: We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months. RESULTS: Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval [CI], 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months. CONCLUSIONS: Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).

Bioaccessibility of Bioactive Compounds of 'Fresh Garlic' and 'Black Garlic' through In Vitro Gastrointestinal Digestion.

Numerous studies have reported health benefits associated with the consumption of fresh and black garlic, which are characterized by the presence of polyphenols and organosulfur compounds (OS). This study aims to analyze the bioaccessibility of the bioactive compounds in fresh and black garlic after in vitro gastrointestinal digestion by monitoring the individual profile of these compounds by ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS). Polyphenols decreased from the beginning of the digestive process, is mainly affected during intestinal digestion. Regarding the OS, the S-alk(en)yl-L-cysteine (SACs) derivatives were more influenced by the acidic conditions of the gastric digestion, while the γ-glutamyl-S-alk(en)yl-L-cysteine (GSAk) derivatives were more susceptible to intestinal digestion conditions in both the fresh and black garlic samples. In conclusion, after in vitro gastrointestinal digestion, the compounds with the highest bioaccessibility were vanillic acid (69%), caffeic acid (52%), γ-glutamyl-S-methyl-L-cysteine sulfoxide (GSMCS) (77%), and S-allylmercapto-L-cysteine (SAMC) (329%) in fresh garlic. Meanwhile, in black garlic, the main bioaccessible compounds were caffeic acid (65%), GSMCS (89%), methionine sulfoxide (262%), trans-S-(1-propenyl)-L-cysteine (151%), and SAMC (106%). The treatment (heating + humidity) to obtain black garlic exerted a positive effect on the bioaccessibility of OS compounds, 55.3% of them remaining available in black garlic, but only 15% in fresh garlic. Polyphenols showed different behavior regarding bioaccessibility.

Women With First-Hand Tobacco Smoke Exposure Have a Higher Likelihood of Having an Unruptured Intracranial Aneurysm Than Nonsmokers: A Nested Case-Control Study.

BACKGROUND: The prevalence of unruptured intracranial aneurysms (UIA) in females who smoke cigarettes and the association between smoking and hypertension with purely incidental UIAs have been unexplored. OBJECTIVE: To obtain the prevalence of UIA among females and to assess the relationship between smoking and hypertension with a diagnosis of incidental UIAs. METHODS: A nested case-control study from a cohort of female patients aged between 30 and 60 yr with a brain magnetic resonance angiography (MRA) between 2016 and 2018. Incidental UIAs were compared to patients with normal MRAs. Smoking was characterized as never or former/current smokers. A logistic regression was used to evaluate the association between smoking, hypertension, or both, with a diagnosis of incidental UIAs. RESULTS: A total of 1977 patients had a brain MRA between 2016 and 2018. From 1572 nonsmoker patients, we encountered 30 with an UIA (prevalence: 1.9%). There were 405 patients with a positive smoking history, and 77 patients harbored an UIA (prevalence: 19%). Of 64 aneurysm patients and 130 random controls eligible for the case control, aneurysm patients were more likely to have a positive smoking history and hypertension compared with healthy controls (60% vs 18%, P ≤ .001; 44% vs 14%, P ≤ .001). A multivariable analysis demonstrated a significant association between a smoking history, hypertension, or both factors with an incidental UIA (odds ratio [OR] 5.8 CI 1.22-11.70; OR 3.8 CI 2.31-14.78; OR 12.6 CI 4.38-36.26; respectively). CONCLUSION: Females who smoke cigarettes have a higher prevalence of UIAs than the general population. Smoking confers a higher risk for having a silent UIA, aggravated by hypertension. This population is an ideal target for potential screening.

Assessing the oncolytic potential of rotavirus on mouse myeloma cell line Sp2/0-Ag14 / Evaluación del potencial oncolítico del rotavirus en la línea celular Sp2/0-Ag14 de mieloma de ratón

Introduction: Cancer is the second leading cause of death in the United States, surpassed only by cardiovascular disease. However, cancer has now overtaken cardiovascular disease as the main cause of death in 12 countries in Western Europe. The burden of cancer is posing a major challenge to health care systems worldwide and demanding improvements in methods for cancer prevention, diagnosis, and treatment. Alternative and complementary strategies for orthodox surgery, radiotherapy, and chemotherapy need to be developed. Objective: To determine the oncolytic potential of tumor cell-adapted rotavirus in terms of their ability to infect and lysate murine myeloma Sp2/0-Ag14 cells. Materials and methods: We inoculated rotaviruses Wt1-5, WWM, TRUYO, ECwt-O, and WTEW in Sp2/0-Ag14 cells and we examined their infectious effects by immunocytochemistry, immunofluorescence, flow cytometry, and DNA fragmentation assays. Results: Rotavirus infection involved the participation of some heat shock proteins, of protein disulfide isomerase (PDI), and integrin ß3. We detected the accumulation of viral antigens within the virus-inoculated cells and in the culture medium in all the rotavirus isolates examined. The rotavirus-induced cell death mechanism in Sp2/0-Ag14 cells involved changes in cell membrane permeability, chromatin condensation, and DNA fragmentation, which were compatible with cytotoxicity and apoptosis. Conclusions: The ability of the rotavirus isolates Wt1-5, WWM, TRUYO, ECwt-O, and WTEW to infect and cause cell death of Sp2/0-Ag14 cells through mechanisms that are compatible with virus-induced apoptosis makes them potential candidates as oncolytic agents.

Introducción. El cáncer es la segunda causa de muerte en los Estados Unidos, solamente superado por la enfermedad cardiovascular. Sin embargo, el cáncer aventaja a la enfermedad cardiovascular como primera causa de muerte en doce países de Europa occidental. Se requieren mejores métodos de prevención, diagnóstico y tratamiento para afrontar el gran desafío que el cáncer representa mundialmente para los sistemas de salud, y se necesita desarrollar estrategias alternativas y complementarias a la cirugía, la radioterapia y la quimioterapia convencionales. Objetivo. Evaluar el potencial oncolítico de rotavirus adaptados a células tumorales por su capacidad para infectar y lisar células Sp2/0-Ag14 de mieloma de ratón. Materiales y métodos. Los aislamientos de rotavirus Wt1-5, WWM, TRUYO, ECwt-O y WTEW se inocularon en células Sp2/0-Ag14 y se examinaron sus efectos infecciosos mediante inmunocitoquímica, inmunofluorescencia, citometría de flujo y ensayos de fragmentación del ADN. Resultados. La infección con los rotavirus Wt1-5, WWM, TRUYO, ECwt-O y WTEW implicó la participación de algunas proteínas de choque térmico, la proteína disulfuro isomerasa y la integrina ß3. La acumulación de antígenos virales intracelulares y extracelulares se detectó en todos los virus utilizados. Los mecanismos de muerte inducidos por los rotavirus en células Sp2/0-Ag14 indujeron cambios en la permeabilidad de la membrana celular, la condensación de cromatina y la fragmentación de ADN, los cuales fueron compatibles con citotoxicidad y apoptosis. Conclusiones. La capacidad de los rotavirus estudiados para infectar y causar la muerte de células Sp2/0-Ag14 mediante mecanismos compatibles con la apoptosis inducida viralmente los convierte en candidatos potenciales para ser utilizados como agentes oncolíticos.

[Anthropometric profile and prevalence of overweight and obesity in Costa Rican urban population (aged 20-65 years old) by sex group: results from the Latin American Study of Nutrition and Health]. / Perfil antropométrico y prevalencia de sobrepeso y obesidad en la población urbana de Costa Rica entre los 20 y 65 años agrupados por sexo: resultados del Estudio Latino Americano de Nutrición y Salud.

INTRODUCTION: Introduction: obesity is a disease that greatly affects the region of the Americas. This condition implies an increase the risk of the developing serious health outcomes such as cardiometabolic disease, type 2 diabetes and some cancers. The prevalence of excess weight in Costa Rica was 59.7 % and 77.3 % in women aged 20 to 44 years old and 45 to 65 years old respectively, and 62,4 % in men aged 20-65 years old, in the period of 2008-2009, however, it is unknown how this condition was evolved. Objective: to describe the anthropometric profile and the prevalence of overweight and obesity in the Costa Rican urban population according to sociodemographic characteristics and level of physical activity. Materials and methods: a representative sample of the urban population was selected between November 2014 and May 2015, comprising 677 people between 20 and 65 years old. Measures of height, weight, and waist and neck circumference were measured and the prevalence of obesity, abdominal and cervical obesity was determined, according to the cut-off points established for each indicator. Results: the prevalence of excess weight (overweight and obesity) was 68.5 % among urban Costa Rican population, being higher for women (73.8 %), and for those participants over 35 years old (82.2 %). A 70.3 % of the population presented abdominal obesity and 46,8 % cervical obesity. Conclusions: in Costa Rica, the prevalence of obesity found is high compared to other regions of the world and has increased in relation to the National Nutrition Survey 2008-2009. The approach to obesity must be prioritized in order to prevent the development of cardiovascular and metabolic diseases and thus reduce the impact of these diseases on the health of the individual and the economic costs of health care.

INTRODUCCIÓN: Introducción: la obesidad es una enfermedad que afecta en gran medida a la región de las Américas. Esta condición implica un aumento de la morbimortalidad y el riesgo de enfermedades crónicas, como las enfermedades cardiovasculares, diabetes tipo 2 y algunos tipos de cáncer. La prevalencia de exceso de peso en Costa Rica fue del 59,7 % y del 77,3 % en mujeres de 20 a 44 años y de 45 a 65 años, respectivamente, y del 62,4 % en hombres de 20-65 años en el periodo 2008-2009; se desconoce cómo ha evolucionado esta condición en la última década. Objetivo: describir el perfil antropométrico y prevalencia de sobrepeso y obesidad en población urbana costarricense según características sociodemográficas y nivel de actividad física. Métodos: entre noviembre 2014 y mayo 2015 se seleccionó una muestra representativa de la población urbana, conformada por 677 personas entre 20 y 65 años. Se realizaron mediciones de talla, peso, circunferencia de cintura y cuello y se determinó la prevalencia de obesidad y la obesidad abdominal y cervical, según los puntos de corte establecidos. Resultados: se encontró una prevalencia de exceso de peso (sobrepeso y obesidad) del 68,5 % en la población urbana costarricense, mayor en mujeres que en hombres (73,8 %), y en personas mayores de 35 años (82,2 %). Además, el 70,3 % de la población presentó obesidad abdominal y el 46,8 % presentó circunferencia de cuello aumentada. Conclusiones: en Costa Rica, la prevalencia de obesidad encontrada es notablemente superior respecto a otras regiones del mundo y se ha incrementado en relación a la Encuesta Nacional de Nutrición 2008-2009, por lo que su abordaje se hace prioritario con el fin de prevenir la incidencia y prevalencia de enfermedades cardiovasculares y metabólicas y disminuir su impacto, tanto para la salud del individuo como en los costes implicados en su atención.

Indications, feasibility, safety, and efficacy of CyberKnife radiotherapy for the treatment of olfactory groove meningiomas: a single institutional retrospective series.

PURPOSE: To assess the safety and efficacy of CyberKnife® radiotherapy (CKRT) for the treatment of olfactory groove meningiomas (OGMs). METHODS: A retrospective review was performed of 13 patients with OGM treated with CKRT from September 2005 to May 2018 at our institution. Nine patients were treated primarily with CKRT, 3 for residual disease following resection, and 1 for disease recurrence. RESULTS: Five patients were treated with stereotactic radiosurgery (SRS), 6 with hypofractionated stereotactic radiotherapy (HSRT), and 2 with fractionated stereotactic radiotherapy (FSRT). The median tumor volume was 8.12 cm3. The median prescribed dose was 14.8 Gy for SRS, 27.3 Gy for HSRT, and 50.2 Gy for FSRT. The median maximal dose delivered was 32.27 Gy. Median post treatment follow-up was 48 months. Twelve of 13 patients yielded a 100% regional control rate with a median tumor volume reduction of 31.7%. Six of the 12 patients had reduced tumor volumes while the other 6 had no changes. The thirteenth patient had significant radiation-induced edema requiring surgical decompression. Twelve patients were alive and neurologically stable at the time of the review. One patient died from pneumonia unrelated to his CKRT treatment. CONCLUSIONS: CKRT appears to be safe and effective for the treatment of OGMs.

Changes in the antioxidant activity and metabolite profile of three onion varieties during the elaboration of 'black onion'.

This study aims to investigate whether the heat treatment applied during the production of black onion, a novel derived product made from fresh onion, produces changes in the content of flavonoids, organosulfur compounds, organic acids, water soluble sugars and amino acids in three onion varieties ('Shallot', 'Chata' and 'Echalion'). The total flavonoid content decreased up to 12-fold in black onions compared with fresh onions while the quantities of isoalliin, the main organosulfur compound in black onions, drastically increased during the process. Moreover, the levels of fructose and glucose significantly increased during the elaboration process, contributing to the sweetness of black onions. The influence of heating on their antioxidant capacity showed a decreasing trend of the ORAC antioxidant activity of onion, while ABTS and DPPH did not show a clear tendency. These results present a comprehensive phytochemical characterization of black onions, highlighting the significant influence of the heating process on their phytochemical composition.

Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy in Essential Tremor: A Comprehensive Lesion Characterization.

BACKGROUND: Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is a novel and effective treatment for controlling tremor in essential tremor patients. OBJECTIVE: To provide a comprehensive characterization of the radiological, topographical, and volumetric aspects of the tcMRgFUS thalamic lesion, and to quantify how they relate to the clinical outcomes. METHODS: In this study, clinical and radiological data from forty patients with medically-refractory essential tremor treated with unilateral tcMRgFUS thalamotomy were retrospectively analyzed. Treatment efficacy was assessed with Clinical Rating Scale for Tremor (CRST). Lesions were manually segmented on T1, T2, and susceptibility-weighted images, and 3-dimensional topographical analysis was then carried out. Statistical comparisons were performed using nonparametric statistics. RESULTS: The greatest clinical improvement was correlated with a more inferior and posterior lesion, a bigger lesion volume, and percentage of the ventral intermediate nucleus covered by the lesion; whereas, the largest lesions accounted for the occurrence of gait imbalance. Furthermore, the volume of the lesion was significantly predicted by the number of sonications surpassing 52°C. CONCLUSION: Here we provide a comprehensive characterization of the thalamic tcMRgFUS lesion including radiological and topographical analysis. Our results indicate that the location and volume of the lesion were significantly associated with the clinical outcome and that mid-temperatures may be responsible for the lesion size. This could serve ultimately to improve targeting and judgment and to optimize clinical outcome of tcMRgFUS thalamotomy.