Histoplasmosis in an immunocompetent host: a rare case report

Histoplasmosis, a systemic mycosis caused by Histoplasma capsulatum manifests clinically in immunocompromised patients as acute or chronic pulmonary infection or as a progressive disseminated disease. In immunocompetent hosts, the disease is usually self-limited or presents as flu-like symptoms. It is endemic in North, Central and South America as well as parts of Europe and Africa. We report a case of a 76-year-old diabetic, HIV negative patient who presented with white nodular patches on the tongue and gingiva which were reported as histoplasmosis on histopathology. He also had idiopathic CD4 lymphocytopenia and thrombocytopenia

Effects of Controlled Defects on the Vortex-Solid Melting Transition of Y-Ba-Cu-O Single Crystals

We report systematic studies of the dc transport properties in proton-irradiated Y-Ba-Cu-O single crystals. We find that the onset of vortex dissipation in moderately irradiated samples is associated with the occurrence of a second-order vortex-solid melting transition. In addition, the decreasing zero-field transition temperature and increasing critical current density with the increasing defects reveal the effects of disorder on reducing the electron mean-free-path and on increasing the pinning density

FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents.

Brain tumours kill more children and adults under 40 than any other cancer. Around half of primary brain tumours are glioblastoma multiforme (GBMs) where treatment remains a significant challenge. GBM survival rates have improved little over the last 40 years, thus highlighting an unmet need for the identification/development of novel therapeutic targets and agents to improve GBM treatment. Using archived and fresh glioma tissue, we show that in contrast to normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA pathway. Importantly, FANCD2 expression levels are strongly associated with tumour grade, revealing a potential exploitable therapeutic window to allow inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue. Using several small molecule inhibitors of the FA pathway in combination with isogenic FA-proficient/deficient glioma cell lines as well as primary GBM cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore provide a strong rationale for the development of novel and potent inhibitors of the FA pathway to improve the treatment of GBMs, which may ultimately impact on patient outcome

Brain monoamine oxidase A activity predicts trait aggression

The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, Mendelian Inheritance in Men database number 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in vivo in healthy nonsmoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the multidimensional personality questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions, the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than one-third of the variability. Because trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression

Vortex-solid melting and depinning in superconducting Y-Ba-Cu-O single crystals irradiated by 3-MeV protons

Compositionally modulated thin films of Cu and Y were prepared in an ultrahigh-vacuum dc ion-beam deposition chamber. The amorphization reaction was monitored by in situ x-ray-diffraction measurements. Growth of amorphous Cu1-xYx is observed at room temperature with the initial formation of a Cu-rich amorphous phase. Further annealing in the presence of unreacted Y leads to Y enrichment of the amorphous phase. Growth of crystalline CuY is observed for T=469 K. Transmission-electron-microscopy measurements provide real-space imaging of the amorphous interlayer and growth morphology. Models are developed, incorporating metastable interfacial and bulk free-energy diagrams, for the early stage of the amorphization reaction

Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer.

Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity of PARP inhibitors in 43 patients with untreated TNBC. The primary end point, decreased Ki67, occured in 12% of TNBC. In secondary end point analyses, HR deficiency was identified in 69% of TNBC with the mutational-signature-based HRDetect assay. Cancers with HRDetect mutational signatures of HR deficiency had a functional defect in HR, assessed by impaired RAD51 foci formation on end of treatment biopsy. Following rucaparib treatment there was no association of Ki67 change with HR deficiency. In contrast, early circulating tumor DNA dynamics identified activity of rucaparib, with end of treatment ctDNA levels suppressed by rucaparib in mutation-signature HR-deficient cancers. In ad hoc analysis, rucaparib induced expression of interferon response genes in HR-deficient cancers. The majority of TNBCs have a defect in DNA repair, identifiable by mutational signature analysis, that may be targetable with PARP inhibitors

Evidence of a Bose-glass transition in superconducting YBa2Cu3O7 single crystals with columnar defects

Experimental evidence of a Bose-glass transition in the vortex state of YBa2Cu3O7 single crystals with columnar defects along the c axis is manifested by the universal critical exponents ν⊥, ν∥ (≡ζν⊥), and z’ derived from the (d’+1)-dimension critical scaling of the frequency-dependent ac resistivity from 102 to 2.5×106 Hz. The Bose-glass transition temperature (TBG) is found to decrease with the increasing angle (θ) between the applied magnetic field and the c axis. The finding that ζ=ν∥/ν⊥=1.1±0.1<d’=2 suggests an incompressible Bose glass at temperatures below TBG

Complete uterine inversion during caesarean section: A case report

Inversion of the uterus through the uterine lower segment incision during a caesarean section is an extremely rare obstetric incident. It consists, though, an emergency complication that is potentially life-threatening, especially in cases of prolonged inversion, because haemodynamic instability and shock may occur. Prompt diagnosis and immediate uterine reversion are the key actions in the management of this serious complication

Foreign body granuloma in the anterior abdominal wall mimicking an acute appendicular lump and induced by a translocated copper-T intrauterine contraceptive device: a case report

<p>Abstract</p> <p>Introduction</p> <p>Intrauterine contraceptive devices may at times perforate and migrate to adjacent organs. Such uterine perforation usually passes unnoticed with development of potentially serious complications.</p> <p>Case presentation</p> <p>A 25-year-old woman of North Indian origin presented with an acute tender lump in the right iliac fossa. The lump was initially thought to be an appendicular lump and treated conservatively. Resolution of the lump was incomplete. On exploratory laparotomy, a hard suspicious mass was found in the anterior abdominal wall of the right iliac fossa. Wide excision and bisection of the mass revealed a copper-T embedded inside. Examination of the uterus did not show any evidence of perforation. The next day, the patient gave a history of past copper-T Intrauterine contraceptive device insertion.</p> <p>Conclusions</p> <p>Copper-T insertion is one of the simplest contraceptive methods but its neglect with inadequate follow-up may lead to uterine perforation and extra-uterine migration. Regular self-examination for the "threads" supplemented with abdominal X-ray and/or ultrasound in the follow-up may detect copper-T migration early. To the best of our knowledge, this is the first report of intrauterine contraceptive device migration to the anterior abdominal wall of the right iliac fossa.</p