Unusual concomitant rearrangements of Cyclin D1 and MYC genes in blastoid variant of mantle cell lymphoma: Case report and review of literature

We report herein a case of blastoid variant mantle cell lymphoma (MCL) with both aberrant phenotype and unusual genetics. Unexpectedly, lymphoma cells were CD5⁻ and CD10⁺. Standard karyotype and FISH techniques showed that tumor cells carried two distinct translocations which had not been reported together in a same tumor. The first translocation juxtaposed the immunoglobulin lambda light chain locus with CCND1 locus, leading to Cyclin D1 overexpression. The second translocation revealed MYC rearrangement with a non-immunoglobulin gene partner located on the short arm of chromosome 4. The interpretation of the case on tissue sections alone could have been challenging. Indeed, the lack of CD5 and expression of CD10 associated with MYC rearrangement detected on interphasic nuclei could support the diagnosis of diffuse large B-cell lymphoma or Burkitt lymphoma. This distinction is also especially important as these lymphoma subtypes require specific treatment.     

Factors that influence parents’ experiences with results disclosure after newborn screening identifies genetic carrier status for cystic fibrosis or sickle cell hemoglobinopathy

Objective

Newborn screening (NBS) identifies genetic carriers for sickle cell hemoglobinopathy and cystic fibrosis. We aimed to identify factors during initial NBS carrier results disclosure by primary care providers (PCPs) that influenced parents’ experiences and reactions.

Methods

Open-ended responses from telephone interviews with 270 parents of carriers were analyzed using mixed-methods. Conventional content analysis identified influential factors; chi-square tests analyzed relationships between factors and parent-reported reactions.

Results

Parents reported positive (35%) or negative (31%) reactions to results disclosure. Parents’ experiences were influenced by specific factors: content messages (72%), PCP traits (47%), and aspects of the setting (30%). Including at least one of five specific content messages was associated (p < 0.05) with positive parental reactions; omitting at least one of four specific content messages was associated (p < 0.05) with negative parental reactions. Parents reported positive reactions when PCPs avoided jargon or were perceived as calm. Parents reported negative reactions to jargon usage and results disclosure by voicemail.

Conclusion

Parents identified aspects of PCP communication which influenced their reactions and results disclosure experiences.

Practice implications

Our findings suggest ways PCPs may improve communication of carrier results. PCPs should provide specific content messages and consider how their actions, characteristics, and setting can influence parental reactions.     

Performances,feasibility and acceptability of nasopharyngeal swab,saliva and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2

European Journal of Clinical Microbiology & Infectious Diseases - Molecular diagnosis on nasopharyngeal swabs (NPS) is the current standard for COVID-19 diagnosis, but saliva may be an...     

Half-marathon running performance is not improved by a rate of fluid intake above that dictated by thirst sensation in trained distance runners

Purpose

It has been demonstrated that exercise-induced dehydration (EID) does not impair, and ad libitum drinking optimizes, cycling time-trial (TT) performance. However, the idea that EID ≥ 2 % bodyweight (BW) impairs endurance performance is well ingrained. No study has tested the impact of EID upon running TT performance. We compared the effects of thirst-driven (TD) vs. programmed fluid intake (PFI) aimed at maintaining EID-associated BW loss <2 % on half-marathon performance.

Methods

Ten trained distance runners underwent, in a randomized, crossover fashion, two, 21.1 km running TTs on a treadmill (30 °C, 42 % relative humidity) while facing a wind speed matching running speed and drinking water (1) according to thirst sensation (TD) or (2) to maintain BW loss <2 % of their pre-exercise BW (PFI), as recommended by the American College of Sports Medicine.

Results

Despite that PFI significantly reduced EID from 3.1 ± 0.6 (TD) to 1.3 ± 0.7 % BW (PFI), mean rectal temperature from 39.4 ± 0.4 to 39.1 ± 0.3 °C, mean body temperature from 38.1 ± 0.4 to 37.7 ± 0.2 °C and mean heart rate from 175 ± 9 to 171 ± 8 bpm, neither half-marathon time (TD 89.8 ± 7.7; PFI 89.6 ± 7.7 min) nor running pace (TD 4.3 ± 0.4; PFI 4.2 ± 0.4 min/km) differed significantly between trials.

Conclusion

Albeit providing trivial cardiovascular and thermoregulatory advantages, in trained distance runners, PFI (1,380 ± 320 mL/h) offers no performance benefits over TD fluid intake (384 ± 180 mL/h) during a half-marathon raced under warm conditions.     

The Glucose Transporter PfHT1 Is an Antimalarial Target of the HIV Protease Inhibitor Lopinavir

Malaria and HIV infection are coendemic in a large portion of the world and remain a major cause of morbidity and mortality. Growing resistance of Plasmodium species to existing therapies has increased the need for new therapeutic approaches. The Plasmodium glucose transporter PfHT is known to be essential for parasite growth and survival. We have previously shown that HIV protease inhibitors (PIs) act as antagonists of mammalian glucose transporters. While the PI lopinavir is known to have antimalarial activity, the mechanism of action is unknown. We report here that lopinavir blocks glucose uptake into isolated malaria parasites at therapeutically relevant drug levels. Malaria parasites depend on a constant supply of glucose as their primary source of energy, and decreasing the available concentration of glucose leads to parasite death. We identified the malarial glucose transporter PfHT as a target for inhibition by lopinavir that leads to parasite death. This discovery provides a mechanistic basis for the antimalarial effect of lopinavir and provides a direct target for novel drug design with utility beyond the HIV-infected population.     

Surface Structure Characterization of Aspergillus fumigatus Conidia Mutated in the Melanin Synthesis Pathway and Their Human Cellular Immune Response

In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of the A. fumigatus conidial surface.