The Influence of Abacavir and Other Antiretroviral Agents on Virological Response to HCV Therapy Among Antiretroviral-Treated HIV-Infected Patients.

BACKGROUND: It remains unclear if certain antiretroviral medications, particularly abacavir, compromise response to HCV therapy. Such data could inform the selection of appropriate antiretrovirals in HIV/HCV-coinfected patients. The aim of this study was to determine if use of abacavir, as well as other antiretrovirals, was associated with reduced response to pegylated interferon (PEG-IFN) plus ribavirin. METHODS: A cohort study was performed among antiretroviral-treated HIV/HCV-coinfected patients initiating PEG-IFN plus ribavirin between January 2001 and June 2007 at six sites in the United States. Abacavir and other antiretrovirals represented exposures of interest. Study outcomes included an early virological response (\u3e or =2 log IU/ml decrease in HCV viral load at 12 weeks) and sustained virological response (undetectable HCV viral load 24 weeks after treatment discontinuation). RESULTS: Among 212 patients, 74 (35%) received abacavir. For patients infected with HCV genotype 1 or 4, no differences were observed between abacavir users and non-users in early virological response (26 [40%] versus 53 [44%]; adjusted odds ratio [OR] 1.00; 95% confidence interval [CI] 0.50-2.00) or sustained virological response (8 [13%] versus 13 [12%]; adjusted OR 1.34; 95% CI 0.50-3.62). Among genotype 2 and 3 patients, rates of early virological response (7 [78%] versus 16 [89%]; OR 0.44; 95% CI 0.05-3.76) and sustained virological response (3 [33%] versus 8 [44%]; OR 0.63; 95% CI 0.12-3.32) were also similar between abacavir users and non-users. No association was found between other antiretrovirals and a lack of early or sustained response. CONCLUSIONS: Use of abacavir or other antiretroviral medications was not associated with reduced early or sustained virological response rates

The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial

The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01(B) vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults.This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01(B)_2 group, N=64) or 3 (F4/AS01(B)_3 group, N=62) doses of F4/AS01(B) or placebo (control group, N=64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4(+) T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks.At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01(B)_2 and control group (0.073 log(10)copies/mL [97.5% confidence interval (CI): -0.088; 0.235]), or F4/AS01(B)_3 and control group (-0.096 log(10)copies/mL [97.5% CI: -0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4(+) T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01(B) recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01(B)_2 group: angioedema). F4/AS01(B) induced polyfunctional F4-specific CD4(+) T-cells, but had no significant impact on F4-specific CD8(+) T-cell and anti-F4 antibody levels.F4/AS01(B) had a clinically acceptable safety profile, induced F4-specific CD4(+) T-cell responses, but did not reduce HIV-1 VL, impact CD4(+) T-cells count, delay ART initiation, or prevent HIV-1 related clinical events

Small extracellular vesicles released during targeted radionuclide therapy : Role in bystander effects

Les effets non ciblés contribuent à l'efficacité de la radiothérapie vectorisée (TRT) du cancer. Induits par le sécrétome des cellules irradiées, ces effets toxiques peuvent être observés à proximité du site d'irradiation (réponse bystander), ou loin du site d’irradiation (réponse systémique). Ici, la contribution potentielle des petites vésicules extracellulaires (sEV) à ces effets a été étudiée dans différents modèles de cancer différents et plusieurs protocoles de TRT, y compris TRT à base d’émetteurs d’électrons Auger ou particules beta.À l'aide de deux protocoles d'isolement différents, nous avons montré que les sEV dérivées des lignées cellulaires de mélanome murin B16F10 et de cancer pancréatique humain Mia PaCa-2 étaient cytotoxiques, comme démontré par la diminution de la survie clonogénique des cellules réceptrices. Une étude plus approfondie des mécanismes de mort cellulaire indique que les Auger sEV dérivés de cellules B16F10 traitées avec TRT Auger, augmentent les dommages à l'ADN dans les cellules réceptrices ainsi que la formation de micronoyaux. L'injection in vivo de Beta sEV, dérivant de cellules B16F10 traitées par TRT beta, dans des souris greffées avec des tumeurs, a été efficace pour retarder la croissance tumorale mais uniquement chez les souris immunocompétentes. Enfin, le contenu moléculaire des sEV a été exploré. Nous avons montré que l'ADN double-brin augmentait légèrement dans les Auger et Beta sEV par rapport aux sEV de cellules contrôle. Cependant, les sEV dérivés de cellules irradiées par des rayonnements X, qui étaient moins toxiques pour les cellules réceptrices, étaient plus enrichies en ADN. Une analyse plus poussée a révélé que les Auger sEV étaient enrichies en céramides par rapport aux sEV contrôle. Il est intéressant de noter que l'inhibition de l'acide sphingomyélinase, une enzyme qui convertit la sphingomyéline en céramide et dont l'activation a été précédemment démontrée après la TRT Auger, non seulement inhibe le transfert de céramide dans les Auger sEV, mais rétablit également la survie clonogénique dans les cellules réceptrices. Une étude protéomique a révélé que les Auger sEV contenaient 37 protéines surexprimées et 36 protéines uniques par rapport aux sEV contrôle, dont plusieurs étaient impliquées dans la voie de signalisation Rac1/JNK. Certains microARN, principalement impliqués dans le cycle cellulaire, ont également été identifiés. Nos résultats établissent le rôle des sEV comme contributeurs aux effets non ciblés dans la TRT. Ce potentiel thérapeutique est conduit par l'activation du système immunitaire pour les Beta sEV et par des mécanismes cytotoxiques et génotoxiques, notamment pour les Auger sEV. Ces mécanismes sont dépendants du céramide et potentiellement d'un réseau complexe de protéines et de microARN transférés par les sEV aux cellules réceptrices.Non-targeted effects contribute to the efficacy of targeted radiotherapy (TRT) of cancer. Triggered by components secreted by irradiated cells, these toxic effects can be observed at a short distance from the irradiation site (bystander response), or at longer distances (systemic response). Here, the potential contribution of small extracellular vesicles (sEV) to these effects has been investigated in different cancer models and TRT regimen, including Auger electrons and beta particle-based TRT.Using 2 different isolation protocols, we showed that sEV derived from B16F10 murine melanoma and Mia PaCa-2 human pancreatic cancer cell lines were cytotoxic as shown by the decrease in clonogenic survival in recipient cells. Further investigation into the mechanisms of cell death showed that Auger sEV derived from B16F10 cells treated with Auger TRT, increase DNA damage in recipient cells as well as the formation of micronuclei.In vivo injection of Beta sEV, deriving from beta TRT-treated B16F10 cells, into tumor-bearing mice was efficient in delaying tumor growth only in immunocompetent mice.Finally, the molecular content of sEV was explored. We showed that dsDNA slightly increased in Auger and Beta sEV compared to control sEV. However, X-irradiation-derived sEV, which were less toxic in recipient cells, were more enriched in dsDNA. Further analysis revealed that Auger sEV were enriched in ceramide compared to control sEV. Interestingly, the inhibition of the acid sphingomyelinase, an enzyme that converts sphingomyelin into ceramide and previously shown to be activated following Auger TRT, not only inhibits ceramide packaging into Auger sEV, but also reestablishes clonogenic survival in recipient cells. A proteomic study revealed that Auger sEV contained 37 overexpressed and 36 unique proteins compared to control sEV, of which several were implicated in Rac1/JNK signaling pathway. Some microRNA, mostly implicated in cell cycle, were identified too.Our results establish the role of sEV as contributors to non-targeted effects in TRT. This therapeutic potential is driven by the activation of the immune system for Beta sEV and by cytotoxic and genotoxic mechanisms, notably for Auger sEV. These mechanisms are dependent on ceramide and potentially on a complex network of proteins and microRNA transferred by sEV to recipient cells

3rd International Arab Forensic Sciences & Forensic Medicine Conference, ASFSFM 2017: Conference Report

The Arab Society for Forensic Sciences and Forensic Medicine (ASFSFM) at Naif Arab University for Security Sciences seeks to present the latest developments in all fields of forensic sciences through holding specialized scientific events and academic activities. This is also achieved through its periodic scientific peer-reviewed journal, the Arab Journal of Forensic Sciences and Forensic Medicine. It also seeks to promote scientific research in all fields of forensic science and forensic medicine, and seeks actively to contribute in holding scientific meetings in accordance with advanced scientific standards, including the 3rd International Arab Forensic Sciences & Forensic Medicine Conference. This important event was attended by scientists and experts from various fields of criminal and forensic sciences from both Arab and non-Arab countries. This conference was a significant scientific accomplishment that contributed to the advancement of forensic sciences and forensic medicine in the Arab world. The conference aimed, in accordance with the vision of Naif Arab University for Security Sciences, to enhance peace, security and justice in Arab societies.  Naif Arab University for Security Sciences, represented by the Arab Society for Forensic Sciences and Forensic Medicine, held the 3rd International Arab Forensic Sciences & Forensic Medicine Conference on the University's campus during the period from 21st to 23rd November 2017. The event included the participation of more than 720 experts in forensic sciences and forensic medicine from 33 countries all over the world. Experts discussed and presented the latest developments in their fields. The conference provided a creative environment for students from both local and international universities to benefit from experts and specialists, and to access the most recent research.  On behalf of His Excellency the president of Naif Arab University for Security Sciences, and the Arab Society for Forensic Sciences and Forensic Medicine, we would like to pay tribute to all scientists and experts who contributed by sharing their scientific researches through lectures, workshops, and posters within this event. We appreciate their contributions that added great value to the subject of the conference

المؤتمر العربي الدولي الثالث لعلوم الأدلة الجنائية والطب الشرعي ASFSFM2017 : تقرير المؤتمر

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A Pictorial Mobile Application for Improving Communication Skills in Non-Verbal Autism

It is estimated that as many as 25 percent of individuals living with autism spectrum disorders are non-verbal. That is, they cannot functionally communicate with others using their voice. Despite that substantial fraction, we still know very little about these individuals, their abilities, and their needs. "We still know very little about the cognitive capabilities of nonverbal people with autism, and how best to help them learn to communicate," said Geri Dawson, Ph.D., Autism Speaks chief science officer. Non-verbal people with autism are usually unable to communicate normally using natural languages. They can, however, learn to communicate through specific symbols and images. Special education instructors have adopted this method of communication to teach non-verbal people with autism. They introduce the symbols and images to them through different methodologies. This learning process appeared to be effective but it is very long. The process is carried out manually and requires a lots of times, dedication, and resources. The instructors should find the materials in different formats and circumstances. They should repeat the lessons several times and normally in a face-to-face framework. We propose in this paper a mobile-based application that allows non- verbal people with autism to learn and communicate with their surroundings using a smart device. They can then be taught to use specific symbols and images through the smart mobile phones. They can form simple words and sentences to express their feelings and needs. The application is flexible and allows the addition of new contents very easily. To assess the progress of the users, different exercises and puzzles are proposed. These allow the users to improve their skills and to continue learning outside the classrooms

A pictorial mobile-based communication application for non-verbal people with autism

Non-verbal people with autism are usually unable to communicate normally using natural languages. They can, however, learn to communicate through specific symbols and images. Special education instructors have adopted this method of communication to teach non-verbal people with autism. They introduce the symbols and images to them through different methodologies. This learning process appeared to be effective but it is very long. The process is carried out manually and requires a lots of times, dedication, and resources. The instructors should find the materials in different formats and circumstances. They should repeat the lessons several times and normally in a face-to-face framework. We propose in this paper a mobile-based application that allows non-verbal people with autism to learn and communicate with their surroundings using a smart device. They can then be taught to use specific symbols and images through the smart mobile phones. They can form simple words and sentences to express their feelings and needs. The application is flexible and allows the addition of new contents very easily. To assess the progress of the users, different exercises and puzzles are proposed. These allow the users to improve their skills and to continue learning outside the classrooms.Scopu

Rapid communication: insights into the role of extracellular vesicles during Auger radioimmunotherapy

International audiencePurpose: Non-targeted effects, including bystander and systemic effects, play a crucial role during Auger targeted radionuclide therapy. Here, we investigated whether small extracellular vesicles (sEVs) produced by irradiated cells could contribute to the bystander cytotoxic effects in vitro and also to therapeutic efficacy in vivo, after their injection in tumor xenografts.Materials and methods: B16F10 melanoma donor cells were exposed to radiolabeled antibodies (Auger radioimmunotherapy, RIT) for 48 h or to X-rays (donor cells). Then, donor cells were incubated with fresh medium for 2 h to prepare conditioned medium (CM) that was transferred onto recipient cells for bystander effect assessment, or used for sEVs enrichment. Resulting sEVs were incubated in vitro with recipient cells for determining bystander cytotoxicity, or injected in B16F10 melanoma tumors harbored by athymic and C57BL/6 mice.Results: In vitro analysis of bystander cytotoxic effects showed that CM killed about 30-40% of melanoma cells. SEVs isolated from CM contributed to this effect. Moreover, the double-stranded DNA (dsDNA) content was increased in sEVs isolated from CM of exposed cells compared to control (not exposed), but the difference was significant only for the X-ray condition. These results were supported by immunodetection of cytosolic dsDNA in donor cells, a phenomenon that should precede dsDNA enrichment in sEVs. However, sEVs cytotoxicity could not be detected in vivo. Indeed, in athymic and in immunocompetent mice that received four intratumoral injections of sEVs (1/day), tumor growth was not delayed compared with untreated controls. Tumor growth was slightly (not significantly) delayed in immunocompetent mice treated with sEVs from X-ray-exposed cells, and significantly with sEVs purified from CM collected after 48 h of incubation. These results highlight the need to determine the optimal conditions, including radiation absorbed dose and sEVs collection time, to obtain the strongest cytotoxic effects.Conclusions: This study demonstrates that sEVs could play a role during Auger RIT through bystander effects in vitro. No systemic effects were observed in vivo, under our experimental conditions. However, X-rays experiments showed that sEVs collection time might be influencing the nature of sEVs, a parameter that should also be investigated during Auger RIT

Estimating Human Impacts on Soil Erosion Considering Different Hillslope Inclinations and Land Uses in the Coastal Region of Syria

Soils in the coastal region of Syria (CRoS) are one of the most fragile components of natural ecosystems. However, they are adversely affected by water erosion processes after extreme land cover modifications such as wildfires or intensive agricultural activities. The main goal of this research was to clarify the dynamic interaction between erosion processes and different ecosystem components (inclination, land cover/land use, and rainy storms) along with the vulnerable territory of the CRoS. Experiments were carried out in five different locations using a total of 15 erosion plots. Soil loss and runoff were quantified in each experimental plot, considering different inclinations and land uses (agricultural land (AG), burnt forest (BF), forest/control plot (F)). Observed runoff and soil loss varied greatly according to both inclination and land cover after 750 mm of rainfall (26 events). In the cultivated areas, the average soil water erosion ranged between 0.14 ± 0.07 and 0.74 ± 0.33 kg/m2; in the BF plots, mean soil erosion ranged between 0.03 ± 0.01 and 0.24 ± 0.10 kg/m2. The lowest amount of erosion was recorded in the F plots where the erosion ranged between 0.1 ± 0.001 and 0.07 ± 0.03 kg/m2. Interestingly, the General Linear Model revealed that all factors (i.e., inclination, rainfall and land use) had a significant (p < 0.001) effect on the soil loss. We concluded that human activities greatly influenced soil erosion rates, being higher in the AG lands, followed by BF and F. Therefore, the current study could be very useful to policymakers and planners for proposing immediate conservation or restoration plans in a less studied area which has been shown to be vulnerable to soil erosion processes