Search Results (8)

Tumor cells are hallmarked by their capacity to undergo unlimited cell divisions, commonly accomplished either by mechanisms that activate TERT or through the alternative lengthening of telomeres pathway. Neuroblastoma is a heterogeneous pediatric cancer, and the aim of this study was to characterize telomere maintenance mechanisms in a high-risk neuroblastoma cohort. All tumor samples were profiled with SNP microarrays and, when material was available, subjected to whole genome sequencing (WGS). Telomere length was estimated from WGS data, samples were assayed for the ALT biomarker c-circles, and selected samples were subjected to methylation array analysis. Samples with ATRX aberration in this study were positive for c-circles, whereas samples with either MYCN amplification or TERT re-arrangement were negative for c-circles. Both ATRX aberrations and TERT re-arrangement were enriched in 11q-deleted samples. An association between older age at diagnosis and 1q-deletion was found in the ALT-positive group. TERT was frequently placed in juxtaposition to a previously established gene in neuroblastoma tumorigenesis or cancer in general. Given the importance of high-risk neuroblastoma, means for mitigating active telomere maintenance must be therapeutically explored. Full article

Nutritional status is a major determinant of hepatocyte injuries associated with changed metabolism and oxidative stress. This study aimed to determine the relations between oxidative stress, bariatric surgery, and a high-fat/high-sugar (HFS) diet in a diet-induced obesity rat model. Male rats were maintained on a control diet (CD) or high-fat/high-sugar diet (HFS) inducing obesity. After 8 weeks, the animals underwent SHAM (n = 14) or DJOS (n = 14) surgery and the diet was either changed or unchanged. Eight weeks after the surgeries, the activity of superoxide dismutase isoforms (total SOD, MnSOD, and CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and lutathione S-transferase, as well as the thiol groups (-SH) concentration, total antioxidant capacity (TAC), total oxidative stress (TOS) levels, and malondialdehyde (MDA) concentration liver tissue were assessed. The total cholesterol, triglycerides (TG), and high-density lipoprotein (HDL) concentrations were measured in the serum. The total SOD and GPX activities were higher in the SHAM-operated rats than in the DJOS-operated rats. The MnSOD activity was higher in the HFS/HFS than the CD/CD groups. Higher CuZnSOD, GST, GR activities, -SH, and MDA concentrations in the liver, and the triglyceride and cholesterol concentrations in the serum were observed in the SHAM-operated rats than in the DJOS-operated rats. The CAT activity was significantly higher in the HFS-fed rats. Lower TAC and higher TOS values were observed in the SHAM-operated rats. Unhealthy habits after bariatric surgery may be responsible for treatment failure and establishing an obesity condition with increased oxidative stress. Full article

The extant research literature is lacking in its focus on community-based responses (CBRs) to sex trafficking involving minors in the juvenile justice system. To address this research gap, the present study draws from 35 interviews with social service and justice system practitioners who work with juvenile justice-involved minors experiencing sex trafficking to examine collaborative responses in two Study Sites. Specifically, protocols to respond to trafficking and collaboration with community partners are explored. Results indicate that a formal protocol engaging a team approach inclusive of multiple community partners is a promising mezzo level response to addressing the sex trafficking of minors involved in the juvenile justice system. Informal and formal relationships, establishing a shared goal, open and ongoing communication, and trust building were also found to enhance community-based responses. Implications include establishing a protocol to respond to sex trafficking in the juvenile court system when sex trafficking is suspected and/or confirmed, which would engage a CBR team involving the survivor, parent(s)/guardian(s), DJO, supervisor, investigator, judge, Children’s Division caseworker, and social services provider(s). Establishing a shared goal within the CBR team and developing a pattern of communication and follow up can facilitate trust building, ultimately benefitting CBRs addressing the sex trafficking of minors involved with the juvenile justice system. Full article

Over-nutrition with cafeteria diet leads to glycemic control failure and subsequent obesity. Bariatric surgery remains the ultimate treatment option, and when complemented with specific dietary protocol, it may mitigate the effects of oxidative stress induced by a cafeteria diet. The study measured antioxidant marker activity: superoxidase dismutase (SOD) and ceruloplasmin (CER), total antioxidant capacity (TAC), and lipid peroxidation marker concentrations: lipofuscin (LS) and malondialdehyde (MDA), in the plasma of 56 Sprague-Dawley rats fed with a cafeteria (HFS) or a control (CD) diet and subjected to duodenojejunal omega switch (DJOS) or control (SHAM) surgery. The diet change after the surgery (CD/HFS or HFS/CD) strongly influenced SOD activity in DJOS- and SHAM-operated rats, but SOD activity was always higher in SHAM-operated rats. Every dietary protocol used in the study increased CER activity, except for the CD/CD combination. Cafeteria diet consumed before or after either of surgeries led to decrease in TAC levels. DJOS and no change in diet reduced MDA levels. DJOS reduced LS levels, but its beneficial effect was deteriorated by selected dietary protocols. The cafeteria diet negatively affected the positive impact of DJOS surgery, but SOD, CER, MDA, and LS were significantly lower in rats that underwent DJOS, suggesting that eight weeks of dietary treatment before and after the surgery did not totally dilapidate the effects of the bariatric treatment. Full article

A preterm infant with central hypoventilation was diagnosed with multifocal neuroblastoma. Congenital anomalies of the autonomic nervous system in association with neuroblastoma are commonly associated with germline mutations in PHOX2B. Further, the ALK gene is frequently mutated in both familial and sporadic neuroblastoma. Sanger sequencing of ALK and PHOX2B, SNP microarray of three tumor samples and whole genome sequencing of tumor and blood were performed. Genetic testing revealed a germline ALK F1174I mutation that was present in all tumor samples as well as in normal tissue samples from the patient. Neither of the patient’s parents presented the ALK variant. Array profiling of the three tumor samples showed that two of them had only numerical aberrations, whereas one sample displayed segmental alterations, including a gain at chromosome 2p, resulting in two copies of the ALK-mutated allele. Whole genome sequencing confirmed the presence of the ALK variant and did not detect any aberrations in the coding or promotor region of PHOX2B. This study is to our knowledge the first to report a de novoALK F1174I germline mutation. This may not only predispose to congenital multifocal neuroblastoma but may also contribute to the respiratory dysfunction seen in this patient. Full article

The liver plays a central role in glucose and fatty acid metabolism and acts as an endocrine organ that secretes hepatokines with diverse systemic effects. The study aimed to examine the influence of duodenojejunal omega switch (DJOS) bariatric surgery in combination with different diets on glucose administration parameters and hepatokines levels. After 8 weeks on high fat, high sugar diet (HFS) or control diets (CD), Sprague–Dawley rats underwent DJOS or SHAM (control) surgery. For the next 8 weeks after the surgery, half of DJOS and SHAM-operated animals were kept on the same diet as before, and half had a diet change. The oral glucose tolerance test (OGTT) was performed three times: 8 weeks before and 4 and 8 weeks after surgery. Fetuin-B, growth differentiation factor-15 (GDF-15), pentraxin 3 (PTX3) plasma levels were analyzed. DJOS surgery had a beneficial effect on oral glucose tolerance test (OGTT) results and the area under the curve (AUC_OGTT). The OGTT results depended on the time elapsed after the surgery, the type of diet used, the surgery performed, and the interaction between these factors. DJOS bariatric surgery reduced fetuin-B and GDF15 plasma levels. Interaction between the type of surgery performed and diet used influenced the fetuin-B and PTX-3 plasma levels. A dietary regime is essential to achieve therapeutic and clinical goals after bariatric surgery. Full article

Obesity and high-fat diet (HF) are prevalent causes of oxidative stress (OS). Duodenal-jejunal omega switch (DJOS) is a bariatric procedure used for body mass reduction, extensively tested in animal models. We studied the long-term impact of bariatric surgery and an HF diet on the oxidative stress markers in erythrocytes and heart muscles of rats. We analyzed superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) activity and malondialdehyde (MDA) concentration in DJOS or SHAM (control) operated rats fed with different dietary protocols (control diet (CD) and high-fat diet (HF)), before and after the surgery (CD/CD, HF/HF, CD/HF, and HF/CD). We observed higher erythrocytes CAT, GST and GPx activity in DJOS-operated (vs. SHAM) rats fed with an HF/HF diet. For DJOS-operated rats, erythrocytes CAT and GPx activity and MDA concentration were significantly lower in CD/CD group. We observed increased heart muscle GR activity in SHAM-operated rats (vs. DJOS bariatric surgery) fed with an HF/HF diet. Change from HF to CD diet increased heart muscle GPx activity after DJOS bariatric surgery. Heart muscle SOD activity was lower in HF/HF and CD/CD groups after DJOS bariatric surgery (vs. SHAM). DJOS surgery significantly reduced heart muscle MDA concentration in HF/HF and HF/CD groups (vs. SHAM). We conclude that the selected dietary patterns had a stronger impact on oxidative stress markers in erythrocytes and heart muscle than DJOS bariatric surgery. Full article

In this paper, we investigate secure communication for a dual-hop multiuser relay network, where a source communication with N ( $N\ge 1$ ) destinations via an untrusted variable gains relay. To exploit multiuser diversity while protecting source’s confidential message, we first propose a joint destination-based jamming and opportunistic scheduling (DJOS) scheme. Then, we derive closed-form approximated and asymptotic expressions of the secrecy outage probability (SOP) for the considered system with DJOS. Furthermore, we determine an asymptotical optimal power allocation (OPA), which minimizes the asymptotic SOP, to further improve the secrecy performance. Our analytical results show that the achievable secrecy diversity order in terms of SOP with fixed power allocation is $min(1,\frac{N}{2})$ , whereas, with OPA, the achievable secrecy diversity order can be improved up to $min(1,\frac{2N}{N+2})$ . This interesting result reveals that OPA can improve the secrecy diversity order of the single-user network. This is intuitive since full diversity order of 1 cannot be achieved when $N=1$ , thus leaving some space for OPA to improve the diversity order. Nevertheless, for $N\ge 2$ , the effect of OPA is to increase the secrecy array gain rather than the secrecy diversity order since full diversity order 1 has been achieved by the OS scheme. Finally, simulation results are presented to validate our analysis. Full article