Consistency and regularity in past-tense verb generation in healthy ageing,Alzheimer's disease,and semantic dementia

Older adults, individuals with dementia of the Alzheimer's type (DAT), and individuals with semantic dementia (SD) produced the past tense of verbs based on present-tense carrier sentences (e.g., Everyday I ding the bell. Yesterday I_____the bell). Both regularity (i.e., whether or not -ed is used for the past tense) and consistency (i.e., the degree to which verbs of similar orthography and phonology in the present tense have similar past tenses to the target) were manipulated. Participants received regular consistent (e.g., land–landed), regular inconsistent (e.g., weed–weeded), irregular consistent (e.g., sting–stung), and irregular inconsistent (e.g., light–lit) verbs. The dependent measures were overall accuracy rates and error rate types (e.g., regularizations, analogies, and other errors). Both consistency and regularity influenced performance. In addition, individuals with DAT showed a disproportionate deficit for inconsistent verbs associated with a high summed frequency of enemies, whereas SD individuals produced disproportionate breakdowns in performance on regular inconsistent, irregular consistent, and irregular inconsistent verbs. These results are consistent with the perspective that semantic/lexical processes are involved in processing the past tense of both irregular verbs and regular inconsistent verbs, and that attention is used to select appropriate responses and control inappropriate responses.     

Treatment of brain metastases from melanoma

Brain metastases from malignant melanoma have a poor prognosis, and treatment can be difficult because of rapid progression of the disease. To help define the treatment of this disease, we reviewed the published literature on brain metastases from melanoma. If a solitary metastasis is present, surgery might be beneficial, especially if systemic disease is absent. Stereotactic radiosurgery is a less invasive, attractive option for solitary or oligometastatic (up to 6) lesions. External beam whole-brain radiation therapy can produce responses and frequently palliates symptoms, but as the sole therapy, it is unlikely to eradicate brain metastases. Chemotherapy may be gaining a role with newer agents that penetrate the blood-brain barrier. Combined modality therapy appears to be the future direction of treatment of multiple metastases.     

Mutations in PIK3CD Can Cause Hyper IgM Syndrome (HIGM) Associated with Increased Cancer Susceptibility

Autosomal dominant gain of function mutations in the gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. Here we describe three patients in two families who were diagnosed with HIGM at a young age and were recently found to carry heterozygous mutations in PIK3CD. These patients had an abnormal circulating B cell distribution featuring a preponderance of early transitional (T1) B cells and plasmablasts. When stimulated in vitro, PIK3CD mutated B cells were able to secrete class-switched immunoglobulins. This finding implies that the patients’ elevated serum IgM levels were unlikely a product of an intrinsic B cell functional inability to class switch. All three patients developed malignant lymphoproliferative syndromes that were not associated with EBV. Thus, we identified a novel subset of patients with PIK3CD mutations associated with HIGM, despite indications of preserved in vitro B cell class switch recombination, as well as susceptibility to non-EBV-associated malignancies.     

Evaluation of the updated Vitek yeast identification data base.

Using 398 isolates of yeasts and yeastlike fungi comprising 9 genera and 26 species, as well as the hyphomycete Geotrichum candidum and the achlorophyllous alga Prototheca wickerhamii, we compared the API 20C yeast identification system with the modified Vitek yeast identification system with an expanded data base. We found 11 discrepancies between the two systems: five (1.3%) of the isolates (Blastoschizomyces capitatus, 1; Candida albicans, 1; Hansenula anomala, 1; Rhodotorula minuta, 2) had biocodes not included in the expanded Vitek data base, and six (1.5%) of the isolates (Candida lusitaniae, 1; Candida parapsilosis, 1; Cryptococcus uniguttulatus, 1; H. anomala, 1; Torulopsis candida, 2) were misidentified by the Vitek system. Overall, the efficacy of the Vitek system compares favorably with that of the API 20C in the identification of clinically important yeasts.     

Reciprocal white matter alterations due to 16p11.2 chromosomal deletions versus duplications

Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention‐deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.2 deletion carriers demonstrating higher body mass index and head circumference, and 16p11.2 duplication carriers demonstrating lower body mass index and head circumference. Here, we use diffusion tensor imaging to elucidate this reciprocal relationship in white matter organization, showing widespread increases of fractional anisotropy throughout the supratentorial white matter in pediatric deletion carriers and, in contrast, extensive decreases of white matter fractional anisotropy in pediatric and adult duplication carriers. We find associations of these white matter alterations with cognitive and behavioral impairments. We further demonstrate the value of imaging metrics for characterizing the copy number variant phenotype by employing linear discriminant analysis to predict the gene dosage status of the study subjects. These results show an effect of 16p11.2 gene dosage on white matter microstructure, and further suggest that opposite changes in diffusion tensor imaging metrics can lead to similar cognitive and behavioral deficits. Given the large effect sizes found in this study, our results support the view that specific genetic variations are more strongly associated with specific brain alterations than are shared neuropsychiatric diagnoses. Hum Brain Mapp 37:2833–2848, 2016. © 2016 Wiley Periodicals, Inc.