Haemogregarina spp. in a wild population from Podocnemis unifilis Troschel, 1848 in the Brazilian Amazonia

The study objectives were to characterize the morphology of the parasitic forms and describe the prevalence and intensity of Haemogregarina spp. in a population of the turtle Podocnemis unifilis as well as to examine the relationships between parasitism and turtle variables such as gender, size, and weight. Samples were taken in the Tapajós and Jamanxim rivers, Itaituba, Pará state, Brazil. Blood was collected from the tail vein of 72 P. unifilis specimens, including 35 males, 36 females, and one unsexed juvenile. The prevalence of Haemogregarina spp. was 98 % (n?=?71). The mean parasite intensity of Haemogregarina spp. was 118 (1–582) parasites/2000 blood cells (6 %). There was no significant difference in the mean parasite intensity between male (137.68?±?121.8, n?=?35) and female turtles (101.42?±?123.59, n?=?35). There was no relationship between parasite intensity and carapace length. Although the relationship between parasite intensity and host body weight was significant, the relationship was weak. This is the first study on Haemogregarina parasitism with a relatively high number of turtles in Brazil.     

Cyclodextrin Reduces Intravenous Toxicity of a Model Compound

Solubilization of new chemical entities for toxicity assessment must use excipients that do not negatively impact drug pharmacokinetics and toxicology. In this study, we investigated the tolerability of a model freebase compound, GDC-0152, solubilized by pH adjustment with succinic acid and complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) to enable intravenous use. Solubility, critical micelle concentration, and association constant with HP-β-CD were determined. Blood compatibility and potential for hemolysis were assessed in vitro. Local tolerability was assessed after intravenous and subcutaneous injections in rats. A pharmacokinetic study was conducted in rats after intravenous bolus administration.GDC-0152 exhibited pH-dependent solubility that was influenced by self-association. The presence of succinic acid increased solubility in a concentration-dependent manner. HP-β-CD alone also increased solubility, but the extent of solubility enhancement was significantly lower than succinic acid alone. Inclusion of HP-β-CD in the solution of GDC-0152 improved blood compatibility, reduced hemolytic potential by ～20-fold in vitro, and increased the maximum tolerated dose to 80 mg/kg.     

Predictive molecular markers in metastases to the central nervous system: recent advances and future avenues

Metastases to the central nervous system (CNS) are common in several cancer types. For most primary tumors that commonly metastasize to the CNS, molecular biomarker analyses are recommended in the clinical setting for selection of appropriate targeted therapies. Therapeutic efficacy of some of these agents has been documented in patients with brain metastases, and molecular testing of CNS metastases should be considered in the clinical setting. Here, we summarize the clinically relevant biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive Cancer Network (NCCN) for the most relevant primary tumor types: lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations), breast cancer (HER2 amplification, steroid receptor overexpression), melanoma (BRAF mutations), and colorectal cancer (RAS mutations). Furthermore, we discuss emerging therapeutic targets including novel oncogenic alterations (ROS1 rearrangements, FGFR1 amplifications, CMET amplifications, and others) and molecular features of the tumor microenvironment (including immune-checkpoint molecules such as CTLA4 and PD-1/PD-L1). We also discuss the potential role of advanced biomarker tests such as next-generation sequencing and “liquid biopsies” for patients with CNS metastases.     

Psychosocial Correlates of Suicidal Ideation in Rural South African Adolescents

Suicide is a prevalent problem among young people in Southern Africa, but prevention programs are largely absent. This survey aimed to identify the behavioral and psychosocial correlates of suicidal ideation among adolescents in Limpopo. A two-stage cluster sample design was used to establish a representative sample of 591 adolescents. Bivariate correlations and multiple linear regression analyses were conducted. Findings show that suicidal ideation is prevalent among adolescents. The psychosocial factors perceived social support and negative feelings about the family and the behavioral factors forced sexual intercourse and physical violence by the partner were found to increase the risk of suicidal ideation. Depression mediated the relationship between these psychosocial and behavioral risk factors and suicidal ideation. This study increased our understanding of the psychosocial and behavioral predictors of adolescent suicidal ideation. The findings provide target points for future intervention programs and call for supportive structures to assist adolescents with suicidal ideation.     

Carotid intima-media thickness among human immunodeficiency virus-infected patients without coronary calcium

Subjects infected with human immunodeficiency virus (HIV) have increased risk for atherosclerosis. Carotid artery intima-media thickness (IMT) assessed using ultrasound and coronary artery calcium (CAC) detected using computed tomography predict cardiovascular risk in the general population; however, their usefulness and comparability in patients with HIV are less well defined. The purpose of this study was to compare IMT and CAC in the detection of atherosclerosis in subjects with HIV. CAC and IMT were measured in 253 HIV-infected and 58 uninfected adults. Associations among HIV-related factors, traditional risk factors, and CAC and IMT were evaluated. The distribution of IMT among subjects with and without CAC was compared. Among the patients with HIV, 37% had detectable CAC compared to 28% of controls (p = 0.19); 16% of the patients with HIV had CAC >100 compared to 5% of controls (p = 0.03). With either detectable or undetectable CAC, HIV-infected subjects had higher IMT compared to controls (1.02 ± 0.34 vs 0.78 ± 0.12 mm, p <0.0001), even after adjustment for traditional risk factors. Among those with undetectable CAC, 34% of patients with HIV had markedly increased IMT (≥1 mm) compared to no controls (p <0.0001). HIV-related factors were associated with IMT but not with CAC. In conclusion, patients with HIV and controls had similar rates of detectable CAC, while absolute CAC scores were modestly higher in the HIV group. Conversely, carotid IMT detected advanced subclinical atherosclerosis in patients with HIV even in the absence of CAC. Thus, with HIV, IMT is associated with disease-related factors and may be a more sensitive indicator of subclinical atherosclerosis than CAC.     

Altered immune function associated with disordered neural connectivity and executive dysfunctions: A neurophysiological study on children with autism spectrum disorders

Previous studies have shown that children with autism spectrum disorders (ASDs) have impaired executive function, disordered neural connectivity, and abnormal immunologic function. The present study examined whether these abnormalities were associated. Seventeen high-functioning (HFA) and 17 low-functioning (LFA) children with ASD, aged 8–17 years, participated voluntarily in the study. The two groups of children were compared on their general intelligence in terms of IQ; executive function as measured by the Hong Kong List Learning Test, D2 Test of Concentration, Five Point Test, Children's Color Trail Test, Tower of California Test, and Go/No-Go task; a non-executive task as measured by the Picture Completion Task; neural connectivity as measured by theta coherence in the anterior and posterior regions; and immunologic function as measured by the level of circulating CD3+ CD8+ suppressor/cytotoxic T lymphocytes in a blood sample. Results on executive function showed that LFA children performed significantly poorer than HFA children as shown on their lower Executive Composite as well as individual executive function scores. However, there was no group difference on the Picture Completion Task. Results on neural connectivity showed that LFA children demonstrated a different pattern of electroencephalography (EEG) coherence from HFA children as shown in the significantly elevated theta coherence in the anterior network, as well as at the left intra-hemispheric (LA-LP) and right-to-left inter-hemisphere (RA-LP) connections of LFA children. In immunologic function, results showed that LFA children had significantly elevated level of suppressor/cytotoxic T lymphocytes (CD3+ CD8+) (p < 0.05). In addition, the executive dysfunction, disordered neural connectivity, and abnormal immunologic function were found to be associated. These results provided some initial evidence to support the notion that immunologic factors are associated with neuronal damage, measureable by EEG coherence and manifested as executive dysfunctions.