Approaches to identifying appropriate medication adherence assessments for HIV infected individuals with comorbid bipolar disorder

Assessing medication adherence in already difficult-to-treat HIV-infected subpopulations presents a unique challenge. The objective of this study was to compare different approaches to assessing medication adherence: (1) electronic medication monitoring, (2) standardized self-report questionnaire, and (3) self-report visual analogue scale, and to determine whether antiretroviral therapy (ART) adherence measures differed for HIV-infected persons with bipolar disorder (HIV+?/BD+) as compared to HIV-infected persons without bipolar disorder (HIV+?/BD-). ART adherence was assessed for 74 HIV-positive participants using the Medication Event Monitoring System (MEMS), AIDS Clinical Trials Group (ACTG) adherence questionnaire, and visual analogue scale (VAS). Participants were classified as adherent or nonadherent on each measure by previously validated cutscores. Correlations and logistic regressions were used to examine associations between adherence measures and demographic and clinical variables. In the HIV+?/BD- group, significant correlations existed between each self-report measure and the MEMS. Males comprised 81% of the study population. Participants averaged 44 years of age and 13 years of education. No significant correlations were found among adherence measures in the HIV+?/BD+ group. Among participants reporting adherence on either self-report measure but classified as nonadherent based on MEMS, 94% had a diagnosis of bipolar disorder. Bipolar disorder was a significant predictor of adherence classification discordance among self-report measures. Our findings suggest that it remains difficult to assess ART adherence among HIV-positive individuals with bipolar disorder. Combined approaches of self-report and objective measures may be the best way to estimate adherence, and may provide the best basis for interventions designed to improve adherence in difficult-to-treat populations.     

Laparoscopic low anterior resection with total mesorectal excision for rectal cancer

Rectal resections are the only treatment with curative intent currently accepted world wide. When performed in elective circumstances, laparoscopic rectal excision is technically feasible in surgical approach of mid-rectal cancer in a considerable number of patients. There are many benefits of the laparoscopic approach to rectal resection such as short hospitalization, less pain, less postoperative complications and improved quality of life. However, one mandatory condition in laparoscopic resection of rectum includes complete excision of the rectum and mesorectum, generally ensuring a minimal distal margin of 2cm and circumferential radial clearance before performing a coloanal anastomosis. Here, we present a laparoscopic approach for rectal cancer treatment consisting in a wide resection of the rectum, including the entire fascia with the enclosed mesentery of the rectum.     

Instrumental conditioning of fast (20- to 50-Hz) oscillations in corticothalamic networks

Cats were instrumentally conditioned to generate grouped fast (20- to 50-Hz) oscillations in motor cortex (area 4). Over seven experimental sessions, there was a spatially selective increased generation of grouped fast oscillations in that electroencephalogram lead. This locally increased generation of fast oscillations in cortex was associated with a widespread increase in synchrony of fast oscillations in thalamocortical networks, as demonstrated by cross-correlations between intracortical, corticothalamic, and intrathalamic field potentials. A three-session extinction period abolished the local increase in generation of grouped fast oscillations and reset the thalamocortical synchrony of fast oscillations to control values. A subsequent series of seven sessions with instrumental conditioning of fast oscillations in visual cortex (area 17) reproduced the results from area 4, with a spatially selective increased generation of grouped fast oscillations in the criterion lead, associated with a widespread increase in thalamocortical synchrony of fast oscillations. In addition to their presence during the conditioning sessions, the changes in synchrony of fast oscillations were expressed during periods of quiet waking, rapid-eye-movement sleep, and nonrapid-eye-movement sleep recorded during the first hour after the end of the conditioning.     

Fiber-Templated 3D Calcium-Phosphate Scaffolds for Biomedical Applications: The Role of the Thermal Treatment Ambient on Physico-Chemical Properties

A successful bone-graft-controlled healing entails the development of novel products with tunable compositional and architectural features and mechanical performances and is, thereby, able to accommodate fast bone in-growth and remodeling. To this effect, graphene nanoplatelets and Luffa-fibers were chosen as mechanical reinforcement phase and sacrificial template, respectively, and incorporated into a hydroxyapatite and brushite matrix derived by marble conversion with the help of a reproducible technology. The bio-products, framed by a one-stage-addition polymer-free fabrication route, were thoroughly physico-chemically investigated (by XRD, FTIR spectroscopy, SEM, and nano-computed tomography analysis, as well as surface energy measurements and mechanical performance assessments) after sintering in air or nitrogen ambient. The experiments exposed that the coupling of a nitrogen ambient with the graphene admixing triggers, in both compact and porous samples, important structural (i.e., decomposition of β-Ca₃(PO₄)₂ into α-Ca₃(PO₄)₂ and α-Ca₂P₂O₇) and morphological modifications. Certain restrictions and benefits were outlined with respect to the spatial porosity and global mechanical features of the derived bone scaffolds. Specifically, in nitrogen ambient, the graphene amount should be set to a maximum 0.25 wt.% in the case of compact products, while for the porous ones, significantly augmented compressive strengths were revealed at all graphene amounts. The sintering ambient or the graphene addition did not interfere with the Luffa ability to generate 3D-channels-arrays at high temperatures. It can be concluded that both Luffa and graphene agents act as adjuvants under nitrogen ambient, and that their incorporation-ratio can be modulated to favorably fit certain foreseeable biomedical applications.     

Colonic thioguanine pro-drug: Investigation of microbiome and novel host metabolism

Thiopurines are analogues of endogenous purines. They are pro-drugs which require the purine salvage pathway to convert them to the active drug nucleotides (TGN). These drugs are used to maintain clinical remission in patients with inflammatory bowel diseases. In our recent Gut paper, we showed that thioguanine worked quickly to improve colitis in the absence in the host animal of the key guanine salvage enzyme, hypoxanthine-guanine-phosphoribosyltransferase (HPRT). Current evidence favours the proposition that active drug delivery to the host lacking HPRT requires translocation of TGN-loaded bacteria across the inflamed mucosal barrier, and most likely delivery by phagocytosis. Alternatively, the efficacy of thioguanine in treating colitis could be mediated by modulation of the community of the microbiota in the intestine, or there are novel host pathways for conversion of the thioguanine pro-drug to TGN.     

Utility of serological markers in predicting the early occurrence of complications and surgery in pediatric Crohn's disease patients

BACKGROUND AND OBJECTIVES: Many Crohn's disease (CD) patients develop complications (fistulae and abscesses), and require surgery, often repeatedly and at variable instances. Identifying serological markers that determine their early or repeated manifestation can enable implementing more aggressive preventive strategies. Our objective was to study the ability of serological markers for predicting development of early (first) and recurrent complications or requirement for surgery. METHODS: Serum anti-Saccharomyces cervisiae (ASCA) (IgA & IgG) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) were assayed close to diagnosis in a pediatric cohort of CD patients identified between 1996 and 1998. At diagnosis and follow-up, information was acquired on demographic and clinical features of disease. Relation between ASCA and clinical events was studied using adjusted Cox-proportional hazards modeling. The relative rates of recurrent clinical events according to the marker measures were compared. RESULTS: The mean age (SD) at diagnosis was 11.2 (3.4) yr. Among 139 patients, 35 (25.9%) and 31 (22.3%) acquired one or more CD related surgery or complication, respectively. Time to occurrence of the first complication was lower among patients ASCA+ (IgA or IgG) (hazards ratio (HR) = 2.33; 95% confidence interval (CI) = 0.99-5.50) and among those with higher ASCA-IgA titers (HR = 1.20; 95% CI = 1.08-1.34). The rates of recurrent complications were higher among those positive or with higher ASCA titers. ASCA did not predict time to undergoing surgery independent of complications, and was unrelated to the occurrence of recurrent surgeries. CONCLUSIONS: Our study shows that serum ASCA measured close to diagnosis can determine the occurrence of early complications in pediatric CD. Preventive treatment targeted toward these susceptible patients could potentially modify the disease course.     

Intraoperative magnetic resonance for the surgical treatment of lesions producing seizures.

Seizures are a major presenting feature of several non-neoplastic cerebral lesions. We reviewed the experience at the Brigham and Women's Hospital, Boston, on the surgical management of benign intracerebral lesions presenting with seizures with intraoperative magnetic resonance imaging (iMRI) guidance. Our aim was to demonstrate that this is an effective and efficient treatment for these lesions. The histories of thirteen patients who presented with seizures secondary to benign intraaxial lesions treated by craniotomy and resection within the iMRI unit at our institution were reviewed. The surgical results, histology and clinical outcomes were reviewed. The mean follow-up was 22.1 months (range 2-48). In all cases, lesions were accurately located with iMRI. After initial macroscopic resection, 5 cases were found to have residual lesion. All had complete radiological resection at the end of the procedure. At follow-up, five patients had no seizures, 5 had rare seizures and the remaining 3 had worthwhile improvement in seizure frequency. Intraoperative MRI is a safe and effective adjunct for the surgical treatment of benign intracerebral lesions presenting with seizures. It provides effective and efficient intraoperative guidance for planning and approach to the lesion and the assurance that the lesion is totally removed. Surgical resection with iMRI may, therefore, provide a useful approach to these lesions.     

Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma

The complex regulation of tumor suppressive gene and its pseudogenes play key roles in the pathogenesis of hepatocellular cancer (HCC). However, the roles played by pseudogenes in the pathogenesis of HCC are still incompletely elucidated. This study identifies the putative tumor suppressor INTS6 and its pseudogene INTS6P1 in HCC through the whole genome microarray expression. Furthermore, the functional studies – include growth curves, cell death, migration assays and in vivo studies – verify the tumor suppressive roles of INTS6 and INTS6P1 in HCC. Finally, the mechanistic experiments indicate that INTS6 and INTS6P1 are reciprocally regulated through competition for oncomiR-17-5p. Taken together, these findings demonstrate INTS6P1 and INTS6 exert the tumor suppressive roles through competing for oncomiR-17-5p. Our investigation of this regulatory circuit reveals novel insights into the underlying mechanisms of hepatocarcinogenesis.