Gastric Adenocarcinoma in the Context of X-linked Agammaglobulinemia

The hallmarks of X-linked Agammaglobulinemia (XLA) are panhypogammaglobulinemia, absent B-cells, and recurrent sinopulmonary and gastrointestinal infections starting at an early age, as well as other infections like cellulitis, meningitis, arthritis and sepsis. A number of non-infectious complications have been reported in these patients, including autoimmune diseases and malignancy, especially lymphomas. Here, we report the case of a 30-year old man who developed gastric adenocarcinoma in the context of XLA. Previous reports of, and hypotheses addressing the development of cancer in patients with XLA, are also summarized. Solid cancer in XLA affects mainly the gastrointestinal tract and seems to be related to chronic infection. A natural evolution can be traced back from gastric adenocarcinoma to megaloblastic anemia due to achlorhydria in the context of chronic infection; periodic endoscopy thus seems justified to detect and treat carcinoma in early stages.     

AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair

While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine. Mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia.     

Standardization of Operator-Dependent Variables Affecting Precision and Accuracy of the Disk Diffusion Method for Antibiotic Susceptibility Testing

Parameters like zone reading, inoculum density, and plate streaking influence the precision and accuracy of disk diffusion antibiotic susceptibility testing (AST). While improved reading precision has been demonstrated using automated imaging systems, standardization of the inoculum and of plate streaking have not been systematically investigated yet. This study analyzed whether photometrically controlled inoculum preparation and/or automated inoculation could further improve the standardization of disk diffusion. Suspensions of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 of 0.5 McFarland standard were prepared by 10 operators using both visual comparison to turbidity standards and a Densichek photometer (bioMérieux), and the resulting CFU counts were determined. Furthermore, eight experienced operators each inoculated 10 Mueller-Hinton agar plates using a single 0.5 McFarland standard bacterial suspension of E. coli ATCC 25922 using regular cotton swabs, dry flocked swabs (Copan, Brescia, Italy), or an automated streaking device (BD-Kiestra, Drachten, Netherlands). The mean CFU counts obtained from 0.5 McFarland standard E. coli ATCC 25922 suspensions were significantly different for suspensions prepared by eye and by Densichek (P < 0.001). Preparation by eye resulted in counts that were closer to the CLSI/EUCAST target of 10⁸ CFU/ml than those resulting from Densichek preparation. No significant differences in the standard deviations of the CFU counts were observed. The interoperator differences in standard deviations when dry flocked swabs were used decreased significantly compared to the differences when regular cotton swabs were used, whereas the mean of the standard deviations of all operators together was not significantly altered. In contrast, automated streaking significantly reduced both interoperator differences, i.e., the individual standard deviations, compared to the standard deviations for the manual method, and the mean of the standard deviations of all operators together, i.e., total methodological variation.     

Is ‘gender disappointment’ a unique mental illness?

Medicine, Health Care and Philosophy - ‘Gender disappointment’ is the feeling of sadness when a parent’s strong desire for a child of a certain sex is not realised. It is...     

Effects of a short workplace exercise program on body composition in women: A randomized controlled trial

Abstract

Physical inactivity and poor diet cause alterations in body composition, which in turn increases risk factors for cardiovascular and metabolic diseases. Sixty-three women from different work environments were randomly assigned to an intervention (n?=?34) or control (n?=?29) group. The intervention was a short-term aerobic exercise program (12?weeks) at their workplace. Participants assigned to the control group did not perform any form of physical exercise. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Diet was assessed using the Mediterranean Diet Quality Questionnaire (KIDMED) and nutrient balance by the Food Frequency Questionnaire. Researchers suggest that a short-term aerobic exercise program produces beneficial effects on body composition.