DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells

<p>Abstract</p> <p>Background</p> <p>The DNA damage by platinum cytostatics is thought to be the main cause of their cytotoxicity. Therefore the measurement of the DNA damage induced by cis- and carboplatin should reflect the sensitivity of cancer cells toward the platinum chemotherapeutics.</p> <p>Methods</p> <p>DNA damage induced by cis- and carboplatin in primary cells of ovarian carcinomas was determined by the alkaline comet assay. In parallel, the reduction of cell viability was measured by the fluorescein diacetate (FDA) hydrolysis assay.</p> <p>Results</p> <p>While in the comet assay the isolated cells showed a high degree of DNA damage after a 24 h treatment, cell viability revealed no cytotoxicity after that incubation time. The individual sensitivities to DNA damage of 12 tumour biopsies differed up to a factor of about 3. DNA damage after a one day treatment with cis- or carboplatin correlated well with the cytotoxic effects after a 7 day treatment (r = 0,942 for cisplatin r = 0.971 for carboplatin). In contrast to the platinum compounds the correlation of DNA damage and cytotoxicity induced by adriamycin was low (r = 0,692), or did not exist for gemcitabine.</p> <p>Conclusion</p> <p>The measurement of DNA damage induced by cis- and carboplatin is an accurate method to determine the in vitro chemosensitivity of ovarian cancer cells towards these cytostatics, because of its quickness, sensitivity, and low cell number needed.</p

Perceptions and Practices of Stimulating Children’s Cognitive Development Among Moroccan Immigrant Mothers

We explored the perceptions of children’s cognitive development among Moroccan Arabic and Berber immigrant mothers who cannot read, who are less educated, middle educated or highly educated in the Netherlands. A series of in-depth interviews was conducted with 22 mothers with young children (mean age = 5 years and 6 months). Qualitative data analyses revealed five major themes that are of significant importance to these mothers: moral attitudes, social values and religiousness; conversation, reading and playing as stimulating activities; importance attached to education; parental expectations; attributions of school success. The parental perceptions about the cognitive development of young children differed according to their own educational level. Mothers who cannot read and mothers with less education emphasized the development of moral, social and religious values for strengthening the cultural identity of their children. This sense of identity would enable them to function within their own cultural group and help them to perform well at school. School success was attributed in large part to a combination of the efforts of the child and the school. Middle and highly educated mothers, on the other hand, valued scholastic development and attributed school success to their own efforts and to the kind of support the child received. The ethnic background of the parents, whether Arabic or Berber, did not make a difference in the perceptions

CD4saurus Rex &HIVelociraptor vs. development of clinically useful immunological markers: a Jurassic tale of frozen evolution

One of the most neglected areas of everyday clinical practice for HIV physicians is unexpectedly represented by CD4 T cell counts when used as an aid to clinical decisions. All who care for HIV patients believe that CD4+ T cell counts are a reliable method to evaluate a patient immune status. There is however a fatalistic acceptance that besides its general usefulness, CD4+ T cell counts have relevant clincal and immunological limits. Shortcomings of CD4 counts appear in certain clinical scenarios including identification of immunological nonresponders, subsequent development of cancer on antiretroviral teatment, failure on tretment simplification. Historical and recently described parameters might be better suited to advise management of patients at certain times during their disease history. Immunogenotypic parameters and innate immune parameters that define progression as well as immune parameters associated with immune recovery are available and have not been introduced into validation processes in larger trials. The scientific and clinical community needs an effort in stimulating clinical evolution of immunological tests beyond "CD4saurus Rex" introducing new parameters in the clinical arena after appropriate validatio

Mitochondrial mosaics in the liver of 3 infants with mtDNA defects

<p>Abstract</p> <p>Background</p> <p>In muscle cytochrome oxidase (COX) negative fibers (mitochondrial mosaics) have often been visualized.</p> <p>Methods</p> <p>COX activity staining of liver for light and electron microscopy, muscle stains, blue native gel electrophoresis and activity assays of respiratory chain proteins, their immunolocalisation, mitochondrial and nuclear DNA analysis.</p> <p>Results</p> <p>Three unrelated infants showed a mitochondrial mosaic in the liver after staining for COX activity, i.e. hepatocytes with strongly reactive mitochondria were found adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue, but not of muscle, demonstrated a decreased activity of complex IV; in both muscle and liver subcomplexes of complex V were seen. Immunocytochemistry of complex IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain revealed severe white matter cavitation in the Pearson case, but only slight cortical atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in leucocytes showed a common deletion in 50% of the mtDNA molecules of the Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome, mtDNA was depleted for 60% in muscle. In the 3rd patient muscular and hepatic mtDNA was depleted for more than 70%. Mutations in the nuclear encoded gene of <it>POLG </it>were subsequently found in both the 2nd and 3rd patients.</p> <p>Conclusion</p> <p>Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the pathogenesis; it indicates whether mtDNA should be assayed. Each time a mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy should be recommended. Mosaics are probably more frequent than observed until now. A novel pathogenic mutation in <it>POLG </it>is reported.</p> <p>Tentative explanations for the mitochondrial mosaics are, in one patient, unequal partition of mutated mitochondria during mitoses, and in two others, an interaction between products of several genes required for mtDNA maintenance.</p

Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression

<p>Abstract</p> <p>Background</p> <p>Cues predictive of food availability are powerful modulators of appetite as well as food-seeking and ingestive behaviors. The neurobiological underpinnings of these conditioned responses are not well understood. Monitoring regional immediate early gene expression is a method used to assess alterations in neuronal metabolism resulting from upstream intracellular and extracellular signaling. Furthermore, assessing the expression of multiple immediate early genes offers a window onto the possible sequelae of exposure to food cues, since the function of each gene differs. We used immediate early gene and proenkephalin expression as a means of assessing food cue-elicited regional activation and alterations in functional connectivity within the forebrain.</p> <p>Results</p> <p>Contextual cues associated with palatable food elicited conditioned motor activation and corticosterone release in rats. This motivational state was associated with increased transcription of the activity-regulated genes <it>homer1a</it>, <it>arc</it>, <it>zif268</it>, <it>ngfi-b </it>and c-<it>fos </it>in corticolimbic, thalamic and hypothalamic areas and of proenkephalin within striatal regions. Furthermore, the functional connectivity elicited by food cues, as assessed by an inter-regional multigene-expression correlation method, differed substantially from that elicited by neutral cues. Specifically, food cues increased cortical engagement of the striatum, and within the nucleus accumbens, shifted correlations away from the shell towards the core. Exposure to the food-associated context also induced correlated gene expression between corticostriatal networks and the basolateral amygdala, an area critical for learning and responding to the incentive value of sensory stimuli. This increased corticostriatal-amygdalar functional connectivity was absent in the control group exposed to innocuous cues.</p> <p>Conclusion</p> <p>The results implicate correlated activity between the cortex and the striatum, especially the nucleus accumbens core and the basolateral amygdala, in the generation of a conditioned motivated state that may promote excessive food intake. The upregulation of a number of genes in unique patterns within corticostriatal, thalamic, and hypothalamic networks suggests that food cues are capable of powerfully altering neuronal processing in areas mediating the integration of emotion, cognition, arousal, and the regulation of energy balance. As many of these genes play a role in plasticity, their upregulation within these circuits may also indicate the neuroanatomic and transcriptional correlates of extinction learning.</p

An engineering perspective of vacuum assisted delivery devices in obstetrics: A review

Complications during childbirth result in the need for clinicians to use ‘assisted delivery’ in over 12% of cases (UK). After more than 50 years in clinical practice, vacuum assisted delivery (VAD) devices remain a mainstay in physically assisting child delivery; sometimes preferred over forceps due to their ease of use and reduced maternal morbidity. Despite their popularity and enduring track-record, VAD devices have shown little evidence of innovation or design change since their inception. In addition, evidence on the safety and functionality of VAD devices remains limited but does present opportunities for improvements to reduce adverse clinical outcomes. Consequently in this review we examine the literature and patent landscape surrounding VAD biomechanics, design evolution and performance from an engineering perspective, aiming to collate the limited but valuable information from a disparate field and provide a series of recommendations to inform future research into improved, safer, VAD systems

Good for the Self:Self-Compassion and Other Self-Related Constructs in Relation to Symptoms of Anxiety and Depression in Non-clinical Youths

This study examined relationships among self-compassion, self-esteem, and self-efficacy and symptoms of anxiety disorders and depression in a sample of 132 non-clinical adolescents aged 12-17 years. The results first of all indicated that the Shortened Self-Compassion Scale for Adolescents was reliable (i.e., all Cronbach's alphas were >.70) and valid in terms of both construct (as demonstrated by a principal components analysis which revealed the hypothesized three-factor structure) and concurrent validity (i.e., as shown by means of positive correlations with self-esteem and self-efficacy). Further, the expected negative correlations were found between self-compassion and anxiety and depression, indicating that higher levels of this self-related construct are associated with lower symptom levels, and vice versa. Of the three components of self-compassion, mindfulness appeared most convincingly related to symptoms of anxiety and depression. Finally, when controlling for other self-related constructs, self-compassion no longer accounted for a significant proportion in the variance of symptom levels. In contrast, self-esteem (depression) and in particular self-efficacy (anxiety and depression) did show unique explanatory power

Machine learning for molecular and materials science

Here we summarize recent progress in machine learning for the chemical sciences. We outline machine-learning techniques that are suitable for addressing research questions in this domain, as well as future directions for the field. We envisage a future in which the design, synthesis, characterization and application of molecules and materials is accelerated by artificial intelligence.</p