Reflection of neuroblastoma intratumor heterogeneity in the new OHC-NB1 disease model

Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.     

Cross‐sectional and longitudinal association of sports participation,media consumption and motor competence in youth

The beneficial associations of physical activity (PA) and sports with motor competence have been well documented. Similarly, high media time has been associated with poor motor competence. Limited information, however, is available on the combined effects of sport participation and media consumption on motor competence. The present study followed 213 Austrian middle‐school students (57% male; age at baseline: 10.4 ± 0.6 years) over a 4‐year period. Annual assessments included the German Motor Test 6‐18, along with self‐reported participation in club sports, time spent watching TV and using the computer. There were no interaction effects between sports participation and media time on motor competence. Club sports participation, however, was associated with higher motor competence, while there was an inverse association between media time and motor competence. Further, motor competence affected future participation in club sports while club sports had limited effects on subsequent motor development. High media time, on the other hand, impaired subsequent motor development, while effects of motor competence on media time were limited. Taken together, these results emphasize the importance of motor competence in the facilitation of sports participation during adolescence. Accordingly, a wide variety of movement experiences should be provided at young ages to promote motor development. In addition, the detrimental effects of media time on motor competence warrant that sedentary behaviors are targeted separately, particularly in youth not participating in sports.     

Teen Use of Marijuana Edibles: A Focus Group Study of an Emerging Issue

Recent research indicates that marijuana-infused food product (i.e., edible) use is becoming nearly as common as smoking marijuana where medical marijuana is available. This study explores edible use among teens. We conducted four focus groups in the San Francisco Bay Area with youth, ages 15–17. The focus groups were divided by gender and whether they used marijuana. Some teens mentioned edible use at school. Youth reported that teens consume edibles, primarily to reduce the likelihood of getting caught. Edibles are also attractive to those who do not like to smoke or have concerns about smoking. Both male and female respondents suggested that females are more likely than males to prefer edibles over smoking, one reason for which may be to avoid smelling like marijuana smoke. For some young women, edibles may be a way to avoid publicly presenting themselves as marijuana users. Findings also suggest that youth have access to edibles through multiple sources. Youth reported that they can purchase edibles at school from other students who either make the edibles themselves or are reselling edibles obtained from dispensaries. Both users and non-users were aware of potentially negative consequences related to edible use. Some youth mentioned that they have heard of youth dying from edibles, and several reported being concerned about the high produced by edibles. Female non-users appeared to be more concerned than others about edibles and compared them to drinks that could be spiked with drugs. However, sentiment among some male marijuana users was that if you cannot handle edibles you should not be using them. These findings suggest that strategies to curb access to edibles and use among youth, such as restricting sales of edibles with strong youth appeal and educating youth on the risks of edibles, will need to be developed.     

Sexual Assistance in Italy: An Explorative Study on the Opinions of People with Disabilities and Would-Be Assistants

Providing assistance services for sexual activity is becoming of increasing importance to the community of people with disabilities and to mental health professionals. Nevertheless, the literature on this topic is sparse. The aim of this study is to explore potential clients’ and assistants’ views, needs, experiences, opinions, and concerns about sexual assistance (SA) in Italy. Twenty-two semi-structured interviews were conducted with 12 people with a congenital physical disability and 10 would-be assistants. A Grounded Theory approach was used to analyze data. Participants with disabilities considered SA useful. Despite most of them having unfulfilled sexual needs, they would prefer to have their sexual needs met within a romantic relationship. Would-be assistants constructed themselves as people who have a “natural aptitude to being useful”. Results suggest that SA services might represent an opportunity for people with disabilities to discover new ways to satisfy their personal needs and to live more autonomously while, at the same time, allowing would-be sexual assistants to fulfill their desire to be helpful. Nevertheless, the use of SA is likely to only be a part of the answer to fulfilling the sexual needs of people with disabilities.     

Social media as a platform for science and health engagement: challenges and opportunities

Social media has become a major platform for debates on science and health. This commentary argues that while social media can present challenges to communicating important health matters, it can also provide health experts a unique opportunity to engage with and build trust among members of the public.     

The ecological risk of heavy metals in sediment from the Danube Delta

The objectives of this study were to assess the sediment contamination with heavy metals and to investigate accordingly the ecological risk posed in the SE of the Danube Delta. Sediments are important in assessing the contamination as they act as reservoirs, transporters and contamination sources. Sediment samples were collected and analysed for lead, cadmium, arsenic and mercury, revealing levels higher than the background, especially for cadmium and mercury (Pb > As > Cd > Hg). Concentrations exceeding the probable effect limit were noticed for arsenic and mercury. The contamination indexes describe the study area as having almost half of the samples as contaminated (pollution load index-PLI 1.04), however the contamination is mostly low-to moderate (modified contamination degree-mCd 1.36). The sediment contamination poses mostly a low ecological risk (RI 94.8). The sediment quality guideline quotient (SQG-Q 0.29) describes a moderate impact, while the probable effect concentration quotient (PEC-Q 0.16) confirms that there are no levels likely to affect the aquatic biota. In our study area, the main Branch of the Danube River and the Secondary Delta are the most affected by contamination, while the narrow, reed abundant channels as the preferred habitat of most aquatic organisms, have a low contamination level.     

Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice

Exendin-4 is now considered as a promising drug for the treatment of cerebral ischemia. To determine the neuroprotective effects of intranasal exendin-4, C57BL/6J mice were intranasally administered with exendin-4 daily for 7 days before middle cerebral artery occlusion (MCAO) surgery. Intranasally administered exendin-4 produced higher brain concentrations and lower plasma concentrations when compared to identical doses administered interperitoneally. Neurological deficits and volume of infarcted lesions were analyzed 24 h after ischemia. Intranasal administration of exendin-4 exhibited significant neuroprotection in C57BL/6 mice subjected to MCAO by reducing neurological deficit scores and infarct volume. The neuroprotective effects of exendin-4 were blocked by the knockdown of GLP-1R with shRNA. However, exendin-4 has no impact on glucose and insulin levels which indicated that the neuroprotective effect was mediated by the activation of GLP-1R in the brain. Exendin-4 intranasal administration restored the balance between pro- and anti-apoptotic proteins and decreased the expression of Caspase-3. The anti-apoptotic effect was mediated by the cAMP/PKA and PI3K/Akt pathway. These findings provided evidence that exendin-4 intranasal administration exerted a neuroprotective effect mediated by an anti-apoptotic mechanism in MCAO mice and protected neurons against ischemic injury through the GLP-1R pathway in the brain. Intranasal delivery of exendin-4 might be a promising strategy for the treatment of ischemic stroke.