Does neurocognitive functioning predict future or persistence of ADHD? A systematic review

Many children with ADHD remain symptomatic in (young) adulthood. It is important to understand what characterizes this persistent ADHD group. Since ADHD has been associated with neurocognitive dysfunctioning on a variety of neurocognitive domains, and many of these domains are influenced by the same risk genes that influence ADHD, neurocognitive functions are a potential predictor for ADHD persistence. We carried out a systematic literature review on the predictive value of neurocognitive functioning for future ADHD. Based on eighteen studies there was no evidence that either automatically controlled (requiring little mental effort; lower level), or more consciously controlled (requiring high levels of mental effort; higher level) neurocognitive functions differentiated ADHD persistence from remittance. In general, both persisters and remitters showed weaker performance than typically developing controls, although the effect was smaller for remitters. Neurocognitive functions measured in childhood predicted ADHD a few years later, regardless of the type of neurocognitive function. Our findings do not support the model of Halperin and Schulz (2006), which suggests a maturation of more consciously controlled neurocognitive functions in ADHD remitters.     

DNA microsatellite instability in hyperplastic polyps,serrated adenomas,and mixed polyps: a mild mutator pathway for colorectal cancer?

AIM: To investigate the distribution of DNA microsatellite instability (MSI) in a series of hyperplastic polyps, serrated adenomas, and mixed polyps of the colorectum. METHODS: DNA was extracted from samples of 73 colorectal polyps comprising tubular adenomas (23), hyperplastic polyps (21), serrated adenomas (17), and mixed polyps (12). The presence of MSI was investigated at six loci: MYCL, D2S123, F13B, BAT-40, BAT-26, and c-myb T22, using polymerase chain reaction based methodology. MSI cases were classified as MSI-Low (MSI-L) and MSI-High (MSI-H), based on the number of affected loci. RESULTS: The frequency of MSI increased in tubular adenomas (13%), hyperplastic polyps (29%), serrated adenomas (53%), and mixed polyps (83%) (Wilcoxon rank sum statistic, p < 0.001). Hyperplastic epithelium was present in nine of 12 mixed polyps and showed MSI in eight of these. MSI was mostly MSI-L. MSI-H occurred in two serrated adenomas and three mixed polyps. Clonal relations were demonstrated between hyperplastic and dysplastic epithelium in four of eight informative mixed polyps. CONCLUSIONS: The findings support the view that hyperplastic polyps may be fundamentally neoplastic rather than hyperplastic. A proportion of hyperplastic polyps may serve as a precursor of a subset (10%) of colorectal cancers showing the MSI-L phenotype, albeit through the intermediate step of serrated dysplasia. This represents a novel and distinct morphogenetic pathway for colorectal cancer.     

HLA haplotypes and birth weight variation: is your future going to be light or heavy?

Birth weight is known to be a direct indicator of perinatal mortality and a clear predictor of adult pathologies too. It has been correlated with several causes of mortality in adulthood: low birth weight with diabetes, nephropathy and cardiovascular diseases and high birth weight with autoimmune diseases and cancer. In genome-wide studies, an extended human leucocyte antigen ( HLA ) region has been linked to birth weight variation. We focused our attention on the HLA haplotypes marked by HLA-A , HLA-B and HLA-DRB1 polymorphisms in 1206 healthy Caucasian newborns belonging to the Cord Blood Bank of Pavia (Italy) and their mothers, aiming to investigate the association between this restricted HLA region and birth weight variation. In our study, the HLA-B*38;DRB1*13 haplotype showed an ascending trend among centiles addressing to the high foetal weight. The HLA-A*02;B*15 haplotype showed a descending trend among centiles addressing to the low foetal weight. Besides the acknowledged correlation between the HLA-A*02 and HLA-B*15 alleles (as well as low birth weight) and type I diabetes and between the HLA-B*38 and HLA-DRB1*13 alleles (as well as high birth weight) and several autoimmune diseases, we cannot predict if our babies, healthy at birth, will suffer from these pathologies during life. Nevertheless, our data point to the HLA telomeric end for markers linked to the low birth weight and to the HLA centromeric end for markers linked to the high birth weight, thus limiting the region involved in birth weight variation, which still represents a useful predictor of disease risk in adulthood.     

Can history, ultrasound, or ELISA chlamydial antibodies, alone or in combination, predict tubal factor infertility in subfertile women?

BACKGROUND: This study aimed to determine whether medical history, transvaginal ultrasound (TVU) or Chlamydia trachomatis antibody testing (CAT), alone or in combination, could provide a non-invasive, clinically useful screening test for predicting tubal factor infertility (TFI) in subfertile women. METHODS: Prior to tubal evaluation, relevant medical history, TVU findings, and enzyme-linked immunosorbent assay (ELISA) IgG CAT results were collected. Sensitivity, specificity, likelihood ratios (LR) and accuracy for predicting TFI, as determined by laparoscopy and dye hydrotubation, were calculated for each test alone, and in parallel and series combination. RESULTS: Thirty per cent (63/207) were diagnosed with TFI. The highest sensitivity (67%, 95% CI: 54-77) included any positive test, yet missed one in three women with TFI. The highest specificity (100%, 95% CI: 97-100) required all three tests positive, but identified only three women. Only the combination of CAT and TVU rated as a good clinical test, but confidence intervals were wide due to the small numbers affected. The combination of CAT or TVU and CAT alone reported the highest accuracy (73%, 95% CI: 66-78), misdiagnosing one in four women. CONCLUSION: Medical history, TVU appearances, and ELISA IgG CAT alone, or in combination, failed to predict accurately TFI in subfertile women.     

Reactive oxygen species in cancer, too much or too little?

It is widely accepted that increased levels of reactive oxygen species (ROS) contribute to carcinogenesis. However, this claim has not been confirmed by experiments. On the contrary, a growing number of studies clearly demonstrate that ROS are normal cellular signals and induce cell differentiation and apoptosis, the opposite processes to cancer, which is dedifferentiated. Thus, it is hypothesized here that decreased levels of ROS may lead to cancer development, which is supported by following observations: (1) the fast-growing tumor produces ROS at a rate only one-third of the rate found with the control liver mitochondria; (2) the reduction in tumor mitochondrial content indicates low level of ROS production; (3) the low levels of manganese superoxide dismutase in tumor mitochondria also indicate decreased production of ROS, because the enzyme activity is induced by ROS; (4) lipid peroxidation capacity was decreased in human colon carcinomas and Yoshida hepatomas; (5) low levels of lipid peroxidation de-inhibit glucose-6-phosphate dehydrogenase, whose activity is always increased in a variety of cancers without exception. Clarification of real role of ROS in cancer may shed light on the understanding of how impairment of mitochondria leads to malignant transformation of normal cells, and offer new types of strategies for cancer prevention and therapy.     

Should we excise? Are there any clinical or histologic features that predict upgrade in papillomas,incidental or non-incidental?

The clinical decision to excise intraductal papilloma (IDP) without atypia diagnosed on biopsy remains controversial. We sought to establish clinical and histologic predictors (if any) which may predict upgrade in IDP. 296 biopsies (in 278 women) with histologic diagnosis of IDP without atypia were retrospectively identified and placed into Incidental (no corresponding imaging correlate), or Non-incidental (positive imaging correlate) groups. 253/296 (85.5%) cases were non-incidental, and 43/296 (14.5%) were incidental. 73.1% (185/253) non-incidental and 48.8% (21/43) incidental cases underwent excision. 12.4% (23/185) non-incidental cases underwent an upgrade to cancer or high-risk lesion; namely 8-Ductal carcinoma in situ (DCIS), 8-atypical ductal hyperplasia (ADH), 6-lobular neoplasia, and 1-flat epithelial atypia. There was no histopathologic feature on the biopsy in the non-incidental group which predicted upgrade; however a past history of atypia was significantly associated with upgrade. 2 of the 21 incidental cases upgraded (1 to ADH and 1 to lobular neoplasia); the former had a past history of ADH. Both incidental upgrades were >1 mm in size, and were not completely excised on the biopsy. None of the incidental cases which appeared completely excised on biopsy upgraded, irrespective of the size on biopsy. These findings suggest that all non-incidental IDPs should be considered candidates for surgical excision, given the 12.4% upgrade rate and no definitive histologic predictors of upgrade. Patients with incidental IDPs (if <1 mm, completely excised on biopsy and with no history of high risk breast lesion) can be spared excision.     

Vaccine for yourself,your community,or your country? Examining audiences’ response to distance framing of COVID-19 vaccine messages

ObjectiveThis study explored the effects of COVID-19 vaccine promotion messages highlighting the benefit at individual, community, and country levels. Based on the cultural theory of risks, we investigated how individuals’ valuation of individualism vs. communitarianism and hierarchical vs. egalitarian social structure affect their responses to vaccine messages.MethodsAn online experiment (N = 702) with four video message conditions (individual-centered, community-centered, country-centered, and no message) was conducted. Participants were asked about their cultural cognition worldview, then were randomly assigned to view one message. Participants also reported their willingness to receive COVID-19 vaccines and support for vaccine mandate.ResultsRespondents were more likely to get vaccinated and support vaccine mandates after viewing an individual-centered message, less with a community-centered message. Individuals who value individualism were more likely to respond positively to individual-centered messages, but those who believe more in communitarianism value were less likely.ConclusionResults showed that individuals are motivated selectively to respond to certain claims that cohere with their worldview and therefore respond differently to vaccine benefit frames.Practice ImplicationsThe results point to the importance of understanding audiences’ worldviews. By identifying this process through hierarchical and individualistic values, properly designed health promotion messages can maximize the desired outcomes.     

Depression or cancer: the choice between serotonin or melatonin?

Stress causes disturbances of monoamine functioning and may result in a serotonin deficiency which is manifested, as depression. In some humans, stress does not, however, cause depression. It is hypothesized that in these individuals, melatonin, which is normally a product of serotonin, may be converted back to its precursor and thus replenish serotonin stores. These people are thus not depressed and are characterized by their pleasant, unassertive nature. Their lowered melatonin levels may, however, signal an increased risk for cancer. It is therefore postulated that unresolved stress results in either depression (with low serotonin) or cancer (as a result of decreased melatonin), depending on individual personality traits and biochemistry.     

Biomarkers for gastric cancer: prognostic,predictive or targets of therapy?

Gastric cancer is an aggressive disease often diagnosed at an advanced stage. Despite improvements in surgical and adjuvant treatment approaches, gastric cancer remains a global public health problem with a 5-year overall survival of less than 25 %. This is a heterogeneous disease, both in terms of biology and genetics, and many prognostic biomarkers have been pointed out in the literature; nevertheless, their application remains debatable. In this review, we opted to give relevance to those biomarkers that have been the subject of studies with significant statistical power, which have been replicated and have been/are in targeted therapy clinical trials and, which as a consequence, have their prognostic and/or predictive value established. Some gastric cancer biomarkers that may help in defining the course of treatment are also discussed. Accepted practical guidelines, wet-lab protocols for the detection of these biomarkers, as well as ongoing and completed clinical trials have been compiled. In summary, clinical approaches based on the combination of correct staging with targeted and conventional systemic therapies may improve gastric cancer patients’ outcome, but are only in their infancy. Some major challenges in identifying reliable prognostic/predictive biomarkers are individual genetic variation and tumour heterogeneity that often influence response to therapy and drug resistance. Prognostic and predictive biomarkers may nevertheless be extremely valuable to correctly stratify gastric cancer patients for treatment and, ultimately, improve survival.