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PURPOSE: This study aimed to determine the proportion of people living with HIV with anti-SARS-CoV-2 IgG antibodies in a sample from a large single HIV center in Munich, Germany, after the first phase of the coronavirus pandemic and to infer the prevalence of SARS-CoV-2 co-infection in people living with HIV. METHODS: Prospective sub-study of the ongoing ArcHIV cohort between May and July 2020. Anti-SARS-CoV-2 IgG antibodies were measured using the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Neuried, Germany); positive and borderline results were re-tested using the recomLine SARS-CoV-2 IgG immunoassay (Mikrogen, Neuried, Germany). Demographic and medical data were extracted from the electronic patient files. RESULTS: Overall, 500 people living with HIV were included in the study (83% male, median age 51 years). Three participants had been diagnosed with COVID-19 prior to study inclusion. Of those, nine were confirmed positive for SARS-CoV-2 IgG antibodies, resulting in an estimated seroprevalence (accounting for sensitivity and specificity of the test) of 1.5% (CI 95%: 0.69; 3.13) for the entire study sample, and 2.2% (CI 95%: 1.1; 3.9) for the subset of the Munich citizens. There were no marked differences for people living with HIV with and without SARS-CoV-2 co-infection. CONCLUSION: The seroprevalence of SARS-CoV-2 co-infection in people living with HIV as found in our study does not seem to exceed previous reports from general populations of 'hot-sport' areas; comparative data from the Munich population can be expected to be published soon. Our data also highlight, once more, the need to do confirmatory testing on positive samples to minimize the impact of false-positive results.
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COVID-19/epidemiología , Coinfección/epidemiología , Punto Alto de Contagio de Enfermedades , Infecciones por VIH/epidemiología , Adulto , Anticuerpos Antivirales/sangre , COVID-19/diagnóstico , Coinfección/diagnóstico , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Alemania/epidemiología , Infecciones por VIH/diagnóstico , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Sensibilidad y Especificidad , Estudios SeroepidemiológicosRESUMEN
BACKGROUND AND PURPOSE: Visual rating scales have limited capacities to depict the regional distribution of cerebral white matter hyperintensities (WMH). We present a regional-zonal volumetric analysis alongside a visualization tool to compare and deconstruct visual rating scales. MATERIALS AND METHODS: 3D T1-weighted, T2-weighted spin-echo and FLAIR images were acquired on a 3T system, from 82 elderly participants in a population-based study. Images were automatically segmented for WMH. Lobar boundaries and distance to ventricular surface were used to define white matter regions. Regional-zonal WMH loads were displayed using bullseye plots. Four raters assessed all images applying three scales. Correlations between visual scales and regional WMH as well as inter and intra-rater variability were assessed. A multinomial ordinal regression model was used to predict scores based on regional volumes and global WMH burdens. RESULTS: On average, the bullseye plot depicted a right-left symmetry in the distribution and concentration of damage in the periventricular zone, especially in frontal regions. WMH loads correlated well with the average visual rating scores (e.g. Kendall's tau [Volume, Scheltens]=0.59 CI=[0.53 0.62]). Local correlations allowed comparison of loading patterns between scales and between raters. Regional measurements had more predictive power than global WMH burden (e.g. frontal caps prediction with local features: ICC=0.67 CI=[0.53 0.77], global volume=0.50 CI=[0.32 0.65], intra-rater=0.44 CI=[0.23 0.60]). CONCLUSION: Regional-zonal representation of WMH burden highlights similarities and differences between visual rating scales and raters. The bullseye infographic tool provides a simple visual representation of regional lesion load that can be used for rater calibration and training.
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Leucoaraiosis/diagnóstico por imagen , Leucoaraiosis/patología , Imagen por Resonancia Magnética/métodos , Anciano , Femenino , Humanos , Imagenología Tridimensional , MasculinoRESUMEN
BACKGROUND: The recreational use of trampolines is an increasingly popular activity among children and adolescents. Several studies reported about radiological findings in trampoline related injuries in children. The following publication presents our experience with MRI for detection of trampoline injuries in children. METHODS: 20 children (mean 9.2 years, range: 4-15 years) who had undergone an MRI study for detection of suspected trampoline injuries within one year were included. 9/20 (45%) children had a radiograph as the first imaging modality in conjunction with primary care. In 11/20 (55%) children MR imaging was performed as the first modality. MR imaging was performed on two 1.5 T scanners with 60 and 70 cm bore design respectively without sedation. In 9/20 (45%) children the injury mechanism was a collision with another child. 7/20 (35%) children experienced leg pain several hours to one day after using the trampoline without acute accident and 4/20 (20%) children described a fall from the trampoline to the ground. RESULTS: All plain radiographs were performed in facilities outside the study centre and all were classified as having no pathological findings. In contrast, MR imaging detected injuries in 15/20 (75%) children. Lower extremity injuries were the most common findings, observed in 12/15 (80%) children. Amongst these, injuries of the ankle and foot were diagnosed in 7/15 (47%) patients. Fractures of the proximal tibial metaphysis were observed in 3/15 children. One child had developed a thoracic vertebral fracture. The two remaining children experienced injuries to the sacrum and a soft tissue injury of the thumb respectively. Seven children described clinical symptoms without an overt accident. Here, fractures of the proximal tibia were observed in 2 children, a hip joint effusion in another 2, and an injury of the ankle and foot in 1 child. There were no associated spinal cord injuries, no fracture dislocations, no vascular injuries and no head and neck injuries. CONCLUSIONS: In the majority of children referred for MR imaging with pain after trampoline MR imaging detects injuries. These injuries are often not visible on plain radiographs. Therefore we recommend a generous use of MR imaging in these children after initial negative plain radiography.
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Imagen por Resonancia Magnética , Recreación , Heridas y Lesiones/diagnóstico por imagen , Heridas y Lesiones/etiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
This paper presents a compact and low-cost on-chip sensor and readout circuit. The sensor achieves high-resolution 5-degrees-of-freedom (DoF) tracking (x, y, z, yaw, and pitch). With the help of an external wire wound sensor, it can also achieve high-resolution 6-degrees-of-freedom (DoF) tracking (x, y, z, yaw, pitch, and roll angles). The sensor uses low-frequency magnetic fields to detect the position and orientation of instruments, providing a viable alternative to using X-rays in image-guided surgery. To measure the local magnetic field, a highly miniaturised on-chip magnetic sensor capable of sensing the magnetic field has been developed incorporating an on-chip magnetic sensor coil, analog-front end, continuous-time ΔΣ analog-to-digital converter (ADC), LVDS transmitter, bandgap reference, and voltage regulator. The microchip is fabricated using 65 nm CMOS technology and occupies an area of 1.06 mm2, the smallest reported among similar designs to the best of our knowledge. The 5-DoF system accurately navigates with a precision of 1.1 mm within the volume-of-intrest (VOI) of 15×15×15 cm3. The 6-DoF system achieves a navigation accuracy of 0.8 mm and an angular error of 1.1 degrees in the same VOI. These results were obtained at a 20 Hz update rate in benchtop characterisation. The prototype sensor demonstrates accurate position tracking in real-life pre-clinical in-vivo settings within the porcine lung of a live swine, achieving a reported worst-case registration accuracy of 5.8 mm.
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Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1-EPVS, 9 for Task 2-Microbleeds and 6 for Task 3-Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1-EPVS and Task 2-Microbleeds and not practically useful results yet for Task 3-Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level.
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Enfermedades de los Pequeños Vasos Cerebrales , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Hemorragia Cerebral , ComputadoresRESUMEN
The echo state property is a key for the design and training of recurrent neural networks within the paradigm of reservoir computing. In intuitive terms, this is a passivity condition: a network having this property, when driven by an input signal, will become entrained by the input and develop an internal response signal. This excited internal dynamics can be seen as a high-dimensional, nonlinear, unique transform of the input with a rich memory content. This view has implications for understanding neural dynamics beyond the field of reservoir computing. Available definitions and theorems concerning the echo state property, however, are of little practical use because they do not relate the network response to temporal or statistical properties of the driving input. Here we present a new definition of the echo state property that directly connects it to such properties. We derive a fundamental 0-1 law: if the input comes from an ergodic source, the network response has the echo state property with probability one or zero, independent of the given network. Furthermore, we give a sufficient condition for the echo state property that connects statistical characteristics of the input to algebraic properties of the network connection matrix. The mathematical methods that we employ are freshly imported from the young field of nonautonomous dynamical systems theory. Since these methods are not yet well known in neural computation research, we introduce them in some detail. As a side story, we hope to demonstrate the eminent usefulness of these methods.
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Modelos Teóricos , Redes Neurales de la ComputaciónRESUMEN
OBJECTIVE: We have previously reported data from the German cohort of the multinational observational prospective RAINBOW survey which assessed the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r)-containing regimens over 48 weeks in routine clinical practice. This analysis presents data from antiretroviral (ART)-naive and pretreated but protease inhibitor (PI)-naive patients treated in a long-term one line (96 weeks) follow-up of the initial study. METHODS: All ART- and PI-naive patients from the initial RAINBOW cohort who had recorded data to one line 96 weeks of treatment were eligible for inclusion in the current analysis. Efficacy assessments included the proportion of patients with HIV-1 RNA <50 and <400 copies/mL and changes in CD4 cell count from baseline to week 96. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 96. For evaluation of efficacy, intent-to-treat analysis, in which missing values were recorded as failure (ITT), and last-observation-carried-forward (LOCF) analysis were used. Metabolic parameters were assessed using LOCF analysis. RESULTS: The analysis included 175 ART-naive and 109 pretreated but PI-naive patients. After 96 weeks, a similar proportion of patients in the ART-naive and in the pretreated but PI-naive group had HIV-1 RNA levels <400 copies/mL (68.0% and 70.6% [ITT], respectively; 96.6% and 90.8% [LOCF], respectively). The proportion of patients with HIV RNA <50 copies/mL was higher in the ART-naive group compared with the pretreated but PI-naive group (61.1% and 56.9% [ITT], respectively; 84.0% and 75.2% [LOCF], respectively). Median change in CD4 cell count from baseline to week 96 was +263 cells/mm3 (IQR 170; 384. LOCF; p<0.0001) in the ART-naive group, and one line +181 cells/mm3 (IQR 60; 309. LOCF; p<0.0001) in the pretreated but PI-naive group. Treatment was well tolerated, with only 2.5% of patients withdrawing from treatment due to side effects. There were no clinically relevant changes in liver enzyme levels. Overall total cholesterol, triglyceride, and low- and high-density lipoprotein levels increased to week 96, although levels remained within normal ranges in the majority of ART-naive and pretreated patients. CONCLUSIONS: This follow-up analysis confirms the long term efficacy and tolerability of SQV/r in ART-naive and pretreated but PI- naive patients in the real-life clinical setting.
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Saquinavir/uso terapéutico , Adulto , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Carga ViralRESUMEN
STUDY OBJECTIVES: Sleep changes are frequent in stroke patients and predict a poor outcome. It remains unclear how sleep influences stroke evolution and recovery. We assessed effects of sleep disruption on brain damage and on the expression of axon sprouting genes after focal cerebral ischemia in rats. DESIGN: 12 h after ischemia induced by occlusion of the middle cerebral artery, rats were subjected to sleep disruption including sleep deprivation for 12h (SDpv12h) and sleep disturbances (SDis) by SDpv12h for consecutive 3 days. Control groups included ischemia without SDpv12h or SDis, sham surgery plus SDis and sham surgery without SDis. Sleep changes were evaluated based on EEG and EMG recordings. MEASUREMENTS AND RESULTS: SDpv12h increased the infarct volume by 40% (SDpv12h 82.8 +/- 10.9 vs. control 59.2 +/- 13.9 mm3, P = 0.008) and SDis by 76% (SDis 58.8 +/- 20.4 vs. control 33.8 +/- 6.3 mm3, P = 0.017). SDpv12h also increased the number of damaged cells, visualized by TUNEL staining, by 137% (SDpv12h 46.8 +/- 15 vs. control 19.7 +/- 7.7/mm2, P < 0.001) and SDis by 219% (SDis 32.9 +/- 13.2 vs. control 10.3 +/- 2.5/mm2, P = 0.002). In addition, SDis significantly elevated the expression of the axonal extension inhibitory molecule neurocan (SDis 14.3 +/- 0.4 vs. control 6.2 +/- 0.1-fold of change, P < 0.001) in the injured hemisphere. CONCLUSIONS: These results provide the first direct evidence for a detrimental impact of sleep disruption on stroke evolution and suggest a potential role of sleep modulating treatments on stroke outcomes.
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Isquemia Encefálica/complicaciones , Privación de Sueño/complicaciones , Análisis de Varianza , Animales , Peso Corporal , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Corticosterona/sangre , Modelos Animales de Enfermedad , Electroencefalografía , Electromiografía , Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Etiquetado Corte-Fin in Situ , Masculino , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neurocano , Proteoglicanos/genética , Proteoglicanos/metabolismo , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Privación de Sueño/genética , Privación de Sueño/metabolismoRESUMEN
BACKGROUND: The RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500-mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of antiretroviral therapy (ART)-naïve and pretreated but protease inhibitor (PI)-naïve patients. METHODS: This was a multicenter, prospective, open-label, 48-week observational cohort study. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48. Efficacy assessments included changes in the proportion of patients with HIV-1 RNA <50 and <400 copies/ml, and changes in CD4 cell count from baseline to week 48. RESULTS: The analysis included 275 ART-naïve and 179 pretreated but PI-naïve patients. The proportion of ART-naïve patients achieving <50 copies/ml by 48 weeks was 53.1% by intent-to-treat (ITT) analysis and 67.3% using last observation carried forward (LOCF) analysis. In pretreated but PI-naïve patients, the proportions achieving <50 copies/ml by 48 weeks were 53.1% (ITT) and 70.4% (LOCF). The median increase in CD4 count at week 48 was +174 cells/mm3 (interquartile range [IQR] 86, 265) in the ART-naïve group and +100 cells/mm3 (IQR 0, 209) in the pretreated but PI-naïve group (p < 0.01 for both; LOCF). Drug-related adverse events were reported in 7.6% of ART-naïve and 2.8% of pretreated but PI-naïve patients. Treatment with SQV/r was stopped in 21.5% of ART-naïve and 17.9% of pretreated but PI-naïve patients (due to side effects in 3.3% and 2.8%, respectively). There were no clinically relevant changes in liver enzyme levels. Overall, the total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein levels increased to week 48, although the levels remained within normal ranges in the majority of patients. CONCLUSIONS: The results of this observational cohort study of treatment with the 500-mg tablet formulation of SQV are consistent with high efficacy and tolerability results seen in controlled studies of SQV/r. This analysis confirms that SQV/r is effective and well tolerated in ART-naïve and pretreated but PI-naïve patients in 'real-world' clinical settings.
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Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Saquinavir/administración & dosificación , Saquinavir/efectos adversos , Administración Oral , Adulto , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , VIH-1/efectos de los fármacos , VIH-1/aislamiento & purificación , Humanos , Lípidos/sangre , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Resultado del Tratamiento , Carga ViralRESUMEN
OBJECTIVE: the RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500 mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of protease inhibitor (PI)-pretreated, but SQV-naive patients. METHODS: multicenter, prospective, open-label, 48 week cohort study. Efficacy assessments included the proportion of patients with HIV-1 RNA <50 and <400 copies/mL and changes in CD4 cell count from baseline to week 48. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48. RESULTS: a total of 426 patients were included in the analysis. The proportion of patients with HIV RNA levels <50 copies/mL at week 48 was 60.3 % (compared with 31.7% at switch to SQV/r) (intent-to-treat, last observation carried forward analysis). After 48 weeks, median CD4 count increased by +61 cells/mm3 from baseline (p<0.01) and 60.3% of patients achieved HIV-1 RNA <50 copies/mL. Median changes in fasting triglyceride levels (stratified according to baseline level) at week 48 were: +14 mg/dL (IQR -8; 57) for patients with baseline triglyceride <200 mg/dL; -50 mg/dL (IQR -139; 0) for baseline triglyceride 200-750 mg/dL, and -656 mg/dL (IQR -1024; 0) for baseline triglyceride >750 mg/dL (p<0.01 for all). Median changes in fasting total cholesterol (TC) levels (stratified according to baseline) were +16 mg/dL (IQR -3; 43) for patients with baseline TC <200 mg/dL (p<0.01), -3 mg/dL (IQR -25; 25) for baseline TC 200-300 mg/dL (p = 0.4), and -47 mg/dL (IQR -87; -4) for baseline TC >300 mg/dL (p<0.01). No significant changes in liver enzymes or bilirubin were observed. SQV treatment was discontinued in 22% of patients, 6% due to side effects. CONCLUSIONS: these data confirm the efficacy and tolerability of SQV/r in PI-experienced, SQV-naive patients treated in a real-life clinical setting. Of particular relevance are the improvements in triglycerides and TC levels observed in patients with baseline grade III-IV elevations.
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/efectos adversos , Encuestas Epidemiológicas/métodos , Saquinavir/administración & dosificación , Saquinavir/efectos adversos , Adulto , Química Farmacéutica/métodos , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Femenino , Alemania , Infecciones por VIH/metabolismo , Humanos , Lipasa/sangre , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: Avoiding abacavir in HIV-infected patients tested positive for HLA-B*5701 reduces the risk of abacavir hypersensitivity reaction (ABC-HSR). Our aim was to assess the costs of clinically suspected HSR and to estimate potential cost savings of implementing prospective HLA-B*5701-screening for HIV-infected patients initiating abacavir/lamivudine fixed-dose combination (ABC/3TC FDC) compared to initiating respective treatment without screening. METHODS: Employing a decision tree model the expected HSR-related costs of screening vs. no screening were estimated from the societal and healthcare payer perspective (reference year 2007). A retrospective standardized assessment of all clinically suspected ABC-HSR cases without screening at 5 German HIV-centres was performed to measure resource consumption. In- and outpatient care, discarded ABC/3TC FDC and concomitant medication were considered. Direct resource utilization was valued using German fees (EBM, G-DRGs). Indirect costs were measured with the human capital approach. Estimates for the HLA-B*5701-prevalence, HSR-incidence, and hospitalization rate were based on clinical trials and cohorts and it was assumed that screening reduces the incidence of clinically suspected ABC-HSR from 10% to 0.5%. RESULTS: Thirty-two ABC-HSR cases were identified from 1998 to 2007. Mean direct and total costs per clinically suspected HSR case were Euro 1,362 and Euro 2,235, respectively. Hospital costs contributed 63.3% to direct costs. Potential cost savings when implementing genetic screening were estimated at Euro 44 and Euro 127 per screened patient, from a healthcare payer or societal perspective. CONCLUSION: HLA-B*5701 screening prior to ABC/3TC FDC initiation prevents significant HSR-related costs per screened patient and is likely to lead to overall net savings.
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Fármacos Anti-VIH/uso terapéutico , Didesoxinucleósidos/efectos adversos , Didesoxinucleósidos/uso terapéutico , Hipersensibilidad a las Drogas/epidemiología , Antígenos HLA-B/análisis , Lamivudine/uso terapéutico , Tamizaje Masivo/economía , Costos y Análisis de Costo , Hipersensibilidad a las Drogas/economía , Quimioterapia Combinada , Alemania , Hospitalización/economía , Humanos , Estudios Retrospectivos , Inhibidores de la Transcriptasa Inversa/uso terapéuticoRESUMEN
The Maillard reaction between reducing sugars and amino acids is a common reaction in foods which undergo thermal processing. Desired consequences like the formation of flavor and brown color of some cooked foods but also the destruction of essential amino acids and the production of anti-nutritive compounds require the consideration of the Maillard reaction and relevant mechanisms for its control. This paper aims to exemplify the recent advances in food processing with regard to the controllability of heat-induced changes in the food quality. Firstly, improved thermal technologies, such as ohmic heating, which allows direct heating of the product and overcoming the heat transfer limitations of conventional thermal processing are presented in terms of their applicability to reduce the thermal exposure during food preservation. Secondly, non-thermal technologies such as high hydrostatic pressure and pulsed electric fields and their ability to extend the shelf life of food products without the application of heat, thus also preserving the quality attributes of the food, will be discussed. Finally, an innovative method for the removal of Maillard reaction substrates in food raw materials by the application of pulsed electric field cell disintegration and extraction as well as enzymatic conversion is presented in order to demonstrate the potential of the combination of processes to control the occurrence of the Maillard reaction in food processing.
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Manipulación de Alimentos/métodos , Productos Finales de Glicación Avanzada/efectos adversos , Reacción de Maillard , Acrilamida/efectos adversos , Aminoácidos/química , Permeabilidad de la Membrana Celular , Culinaria/métodos , Sacarosa en la Dieta/química , Campos Electromagnéticos , Alimentos/efectos adversos , Microbiología de Alimentos , Conservación de Alimentos/métodos , Productos Finales de Glicación Avanzada/aislamiento & purificación , Productos Finales de Glicación Avanzada/metabolismo , Calor , Humanos , Presión HidrostáticaRESUMEN
This research aims to evaluate whether the electroporation of Rhodotorula glutinis fresh biomass improved the subsequent extraction of carotenoids from dry biomass using supercritical CO2 and traditional solvent extraction. Supercritical CO2 extraction yields were low after all treatments assayed. Similarly, solvent extraction of carotenoids from untreated or PEF treated cells that were immediately freeze-dried after the pre-treatment was neither effective (extraction yield < 20% total content). Conversely, PEF-treatment and subsequent intermediate incubation in aqueous buffer for 24 h, followed by freeze-drying and extraction, led to a large improvement with the three solvents assayed (acetone, hexane, ethanol). Ethanol was the most efficient, reaching an extraction yield of 80% of total carotenoid, which represents a recovery of 267 µg/gdw. Torularhodin esters constituted the main carotenoid found in the extracts. This is of great interest, as ethanol is eco-friendly solvent and potential applications of torularhodin range from food to medical purposes.
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The MONARK study was a pilot randomized trial comparing the safety and efficacy of lopinavir-ritonavir (LPV/r) monotherapy to those of LPV/r-zidovudine-lamivudine triple therapy for antiretroviral-naïve human immunodeficiency virus type 1 (HIV-1)-infected patients. Resistance testing was performed at the time of initial screening and at the time of virological failure (defined to include low-level viremia with >50 and <400 HIV-1 virus RNA copies/ml of plasma). Changes from the baseline sequences, including mutations noted on the 2008 International AIDS Society-USA list of resistance-associated protease mutations, were considered. Drug resistance testing was performed for 38 patients (5 of 53 on triple therapy and 33 of 83 on monotherapy). By week 96 (W96), virus samples from 18 of 33 patients in the monotherapy arm showed changes from baseline sequences, and 5 of these patients had viruses with major protease inhibitor (PI) resistance-associated mutations (M46I at W40, L76V at W48, M46I and L76V at W48, L10F and V82A at W72, and L76V at W84). Data on virus phenotypes detected at the time of initial screening and the time of virological failure were available for four patients in whom major PI resistance mutations developed, and these data revealed a mean increase of 2.2-fold (range, 0.75- to 4.6-fold) in the LPV 50% inhibitory concentration. All three patients in whom the L76V PI resistance mutation developed were infected with HIV-1 subtype CRF02_AG. In the triple-therapy group, no major PI resistance mutation was selected among the three patients with protease changes by W48. No association between the baseline CD4 cell count and the viral load, the W4 and final viral loads, or the final LPV trough concentration and the emergence of a major PI resistance mutation was found. Major PI resistance-associated mutations were detected in 5 (6%) of 83 patients treated with LPV/r monotherapy, suggesting that LPV/r monotherapy is an inappropriate first option. The mutation L76V may be considered in further studies of lopinavir resistance.
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Inhibidores de la Proteasa del VIH/uso terapéutico , Lamivudine/uso terapéutico , Pirimidinonas/uso terapéutico , Ritonavir/uso terapéutico , Zidovudina/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Humanos , Lopinavir , Resultado del TratamientoRESUMEN
Granular materials display a variety of behaviors that are in many ways different from those of other substances. They cannot be easily classified as either solids or liquids. This has prompted the generation of analogies between the physics found in a simple sandpile and that found in complicated microscopic systems, such as flux motion in superconductors or spin glasses. Recently, the unusual behavior of granular systems has led to a number of new theories and to a new era of experimentation on granular systems.
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Vibrations in a granular material can spontaneously produce convection rolls reminiscent of those seen in fluids. Magnetic resonance imaging provides a sensitive and noninvasive probe for the detection of these convection currents, which have otherwise been difficult to observe. A magnetic resonance imaging study of convection in a column of poppy seeds yielded data about the detailed shape of the convection rolls and the depth dependence of the convection velocity. The velocity was found to decrease exponentially with depth; a simple model for this behavior is presented here.
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OBJECTIVE: In this paper, we describe the main objectives, the study design and the onset of the patient cohort of the German Competence Network for HIV/AIDS (KompNet) (www.kompetenznetz-hiv.de). Furthermore, we depict sociodemographic and clinical baseline characteristics and an estimation of the coverage and representativity as to the composition of persons living with HIV/AIDS (PLWHA) in Germany. METHODS: The KompNet cohort is an open, retrospective and prospective, multicenter, disease-specific and nationwide cohort study that started gathering data in June 2004. Semi-annually, follow up visits of the patients are documented, covering clinical and sociodemographic data. At enrolment and three years afterwards, an EDTA-sample is taken; a serum-sample is taken at every follow up visit. RESULTS: As of 14.9.2008, a total of 15,541 patients were enrolled by 44 documenting sites. In September 2007, the cohort size was reduced to 10 outpatient clinics and fifteen private practitioners, covering a total of 9,410 patients. The documentation of these patients comprises 24,117 years of follow up-time since enrolment (mean: 2.6 years), 62,862 person years inclusive data documented retrospectively on course of HIV-infection and combined antiretroviral therapy (cART, mean: 6.7 years). 1,008 patients (10.7%) were lost to follow up and 175 (1.9%) died since enrolment. 84.9% of patients were men. Main risks of transmission were sex between men (MSM: 62.9%), heterosexual contacts (18.4%), intravenous drug use (IVDU: 7.0%) and origin from a high prevalence country (HPL: 5.2%). Mean age was 45 years. CONCLUSION: The KompNet cohort covers about a quarter of all patients being under treatment in Germany. The composition of the cohort represents well the most important risks of transmission in Germany. The cohort contains a high proportion of patients being older than 49 years (28.1%). On basis of its comprehensive database and its biomaterials banks, the KompNet cohort serves as an important instrument to monitor and analyse the effects of combined antiretroviral therapy (cART) in Germany, interdigidating basis, clinical and psychosocial research in view to translational research.
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Infecciones por VIH/epidemiología , VIH-1/patogenicidad , Adulto , Antivirales/uso terapéutico , Estudios de Cohortes , Redes Comunitarias/organización & administración , Femenino , Alemania/epidemiología , Infecciones por VIH/terapia , Infecciones por VIH/transmisión , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To investigate if early treatment of primary HIV-1 infection (PHI) reduces viral set point and/or increases CD4 lymphocytes. METHODS: Analysis of two prospective multi-centre PHI cohorts. HIV-1 RNA and CD4 lymphocytes in patients with transient treatment were compared to those in untreated patients. Time to CD4 lymphocyte decrease below 350/ microl after treatment stop or seroconversion was calculated using Kaplan-Meier and Cox-PH-regression analyses. RESULTS: 156 cases of PHI were included, of which 100 had received transient HAART (median treatment time 9.5 months) and 56 remained untreated. Median viral load (563000 cop/ml vs 240000 cop/ml; p<0.001) and median CD4 lymphocyte (449/ microl vs. 613/ microl; p<0.01) differed significantly between treated and untreated patients. Median viral load was 38056 copies/ml in treated patients (12 months after treatment stop) and 52880 copies/ml in untreated patients (12 months after seroconversion; ns). Median CD4 lymphocyte change was +60/ microl vs. -86/ microl (p = 0.01). Median time until CD4 lymphocytes decreased to <350/ microl (including all patients with CD4 lymphocytes <500/ microl during seroconversion) was 20.7 months in treated patients after treatment stop and 8.3 months in untreated patents after seroconversion (p<0.01). Cox-PH analyses adjusting for baseline VL, CD4 lymphocytes, stage of early infection and symptoms confirmed these differences. CONCLUSIONS: Treatment during PHI did not lower viral set point. However, patients treated during seroconversion had an increase in CD4 lymphocytes, whereas untreated patients experienced a decrease in CD4 lymphocytes. Time until reaching CD4 lymphocytes <350/ microl was significantly shorter in untreated than in treated patients including patients with CD4 lymphocytes <500/ microl during seroconversion.