The concomitant presence of del(5q) and JAK2V617F mutation is an infrequent event which occurs in rare patients with peculiar cytogenetic, molecular, morphological and clinical features, resembling ...those of both myelodysplastic syndromes and myeloproliferative neoplasms. Lenalidomide may induce rapid, profound, and long-lasting responses in a subset of these patients. However, the mechanism(s) by which the drug acts in these conditions remain not completely elucidated. A new case report and a review of all cases published so far in this setting are provided. Furthermore, the possibility of categorizing - from a clinical, pathological, and biological point of view - for at least some of these patients as a potential distinct entity is discussed.
Anxiety disorders affect nearly twice as many women as men. However, little is known regarding sex-dependent developmental behavioral differences and whether there is an association with later life ...anxiety disorders. The present study assessed the developmental-behavioral milestones (DBMs) and their relationship with later life anxiety-like behaviors by comparing postnatal ultrasonic vocalizations (USVs) with open field (OF), elevated plus maze (EPM), and light/dark (LD) anxiety test outcomes using the serotonin 1A receptor knockout (KO) mouse model of anxiety. The USVs and DBMs (i.e., grasping, righting, and startle reflexes) were examined on postnatal day 6 (P6), P8, and P10. Adult anxiety-like behaviors were examined on P60 to compare the genotype and sex-dependent differences in anxiety-like behaviors and to correlate them with the USVs. The total number of USVs observed on P8 correlated with later life anxiety-like behaviors in a genotype-, age-, and sex-dependent manner. Interestingly, female KO (KOF) mice exhibited elevated levels of anxiety-like behavior within the OF, EPM, and LD tests. Additionally, an investigation of the USV subtypes, as well as USV sequence structure and repertoire variation, revealed that the KOF mice produced less complex USVs and complex USV-containing sequences on P10. The present study provides an intriguing, predictive "P8/10-USV-to-P60" anxiety-like behavioral model that may prove useful in future characterization, psychopharmacology, and drug rescue studies directed towards sex-specific anxiety treatment.
To analyze dietary supplement usage data from 494 older adults, aged 65 to 101 years.
Community dwellers living independently of institutionalized care.
All dietary supplements, including botanicals, ...were recorded to aid in assessing the health status of older adults.
1) 224 individuals enrolled in a study that follows the health of persons 85 years and older (oldest-old) in Klamath County, a non-metropolitan area in southern Oregon; 2) 134 participants of oldest-old age living in the metropolitan Portland area, enrolled in a randomized clinical trial of GBE biloba extract (GBE) for dementia prevention; and 3) 136 participants, ages 65-85 years (young-old), also of the Portland area, enrolled in a study of the effects of yoga and exercise on cognition.
Data verified from labels, not from self-report.
Of the participants, 70.6% used dietary supplements. Women took supplements more often than men, and usage decreased with age. A greater percentage, 67.4%, of the non-metropolitan oldest-old took supplements, compared to 56.7% of the metropolitan oldest-old. The greatest usage, 89.7%, was in the metropolitan young-olds. All of these percentages exceed those for comparable age groups in national representative surveys.
Dietary supplement usage by older adults in these studies in Oregon exceeded that in other reports and may reflect high interest in complementary and alternative medicine. This report confirms the results of other studies showing that elderly adults, particularly women, use dietary supplements more than other segments of the US population. Researchers and clinicians should be aware of this pattern and potential conflicts with research design or treatment regimen intended for older people.
Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that ...childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development.
The development of a IgGk monoclonal gammopathy after a phase of bone marrow aplasia following chemotherapy is described in a patient suffering from biphenotypic acute leukemia (BAL). Paraprotein was ...followed by the relapse of the disease and disappeared during a further chemotherapy. Paraprotein could have been caused by an additional chemotherapy-induced genetic mutation or by a dysfunction in T-B cooperation observed in the phase of reconstitution of the immune system after medullar aplasia.
We report a rare case of a patient with multiple myeloma who developed hyperamylasemia not associated to hyperamylasuria and without symptoms of pancreatic or salivary disease. This condition ...suggested the occurrence of macroamylasemia, consisting of macromolecules of amylase bound with immunoglobulins, which are not filtered by the kidneys. Hyperamylasemia was not present at the diagnosis of myeloma and appeared at the relapse of the disease, simultaneously with the appearance of an additional γ -chain oligoclonal component, suggesting a possible role of these chains in producing macroamylasemia. To our knowledge, this is the first report of macroamylasemia in a patient with multiple myeloma.
Aberrant expression of the presynaptic serotonin 1A receptor (5-HT1A -R) because of a polymorphism in the 5-HT1A -R gene is associated with severe depression in human, whereas its absence up to ...postnatal day 21 (P21) in the forebrain of mice results in heightened anxiety in adulthood. These observations collectively indicate that the 5-HT1A -R has a crucial role in brain development. To understand the mechanistic underpinnings of this phenomenon, we used organotypic slice cultures of hippocampi from C57BL6 mice (C57) at P15, which coincides with the peak of neonatal synaptogenesis. Stimulation of the hippocampal 5-HT 1A -R caused a dramatic increase in PSD95 expression and dendritic spine and synapse formation through sequential activation of the mitogen-activated protein kinase isozymes Erk1/2 and protein kinase C (PKC). Intrahippocampal infusion of 5-HT1A -R agonists and signaling inhibitors at P15 revealed that the same pathway through PKCα augments PSD95 expression and synaptogenesis in vivo in 24 h in both C57 as well as Swiss Webster mice. Furthermore, intrahippocampal infusion of the antidepressant fluoxetine, a serotonin reuptake inhibitor, also augmented PSD95 expression and synaptogenesis through the same pathway. This increased synaptogenesis was observed even 5 days after treatment. Finally, compared with the wild type, the 5-HT 1A -R(-/-) mice harbor significantly less synapses in the hippocampus, but infusion of the PKC-stimulator and Alzheimer drug bryostatin into the 5-HT1A -R(-/-) mice to bypass the non-existent 5-HT1A -R boosted PSD95 expression and synaptogenesis. The elucidated signaling cascade explains how 5-HT1A -R regulates hippocampal sculpting and function, which may determine the affective phenotype of an adult.
Coagulase-negative staphylococci and Staphylococcus aureus colonize similar niches in mammals and conceivably compete for space and nutrients. Here, we report that a coagulase-negative ...staphylococcus, Staphylococcus chromogenes ATCC43764, synthesizes and secretes 6-thioguanine (6-TG), a purine analog that suppresses S. aureus growth by inhibiting de novo purine biosynthesis. We identify a 6-TG biosynthetic gene cluster in S. chromogenes and other coagulase-negative staphylococci including S. epidermidis, S. pseudintermedius and S. capitis. Recombinant S. aureus strains harbouring this operon produce 6-TG and, when used in subcutaneous co-infections in mice with virulent S. aureus USA300, protect the host from necrotic lesion formation. Used prophylactically, 6-TG reduces necrotic skin lesions in mice infected with USA300, and this effect is mediated by abrogation of toxin production. RNAseq analyses reveal that 6-TG downregulates expression of genes coding for purine biosynthesis, the accessory gene regulator (agr) and ribosomal proteins in S. aureus, providing an explanation for its effect on toxin production.
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