Notes

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These technical standards were developed as a resource for diagnostic laboratory practices in acylcarnitine analysis, interpretation, and reporting.Acute myeloid leukemia (AML) is a common adult leukemia often arising from a preexistent myelodysplastic syndrome (MDS). High mortality rates of AML are caused by relapse and chemoresistance; therefore, we analyzed the role of P2X7 receptor (P2X7R) splice variants A and B in AML progression and response to chemotherapy. The expression of P2X7RA and P2X7RB was investigated in samples obtained from MDS and AML untreated subjects or AML patients in relapse or remission after chemotherapy. Both P2X7RA and P2X7RB were overexpressed in AML versus MDS suggesting a disease-promoting function. However, in relapsing patients, P2X7RA was downmodulated, while P2X7RB was upmodulated. Treatment with daunorubicin (DNR), one of the main chemotherapeutics for AML, upregulated P2X7RB expression while reducing P2X7RA mRNA in AML blasts. PDGFR inhibitor Interestingly, DNR administration also caused ATP release from AML blasts suggesting that, following chemotherapy, activation of the receptor isoforms via their agonist will be responsible for the differential survival of blasts overexpressing P2X7RA versus P2X7RB. Indeed, AML blasts expressing high levels of P2X7RA were more prone to cell death if exposed to DNR, while those overexpressing P2X7RB were more vital and even protected against DNR toxicity. These data were reproducible also in HEK-293 cells separately expressing P2X7RA and B. P2X7RA facilitation of DNR toxicity was in part due to increased uptake of the drug inside the cell that was lost upon P2X7RB expression. Finally, in an AML xenograft model administration of DNR or the P2X7R antagonist, AZ10606120 significantly reduced leukemic growth and coadministration of the drugs proved more efficacious than single treatment as it reduced both P2X7RA and P2X7RB levels and downmodulated c-myc oncogene. Taken together, our data suggest P2X7RA and P2X7RB as potential prognostic markers for AML and P2X7RB as a therapeutic target to overcome chemoresistance in AML relapsing patients.BACKGROUND Mucormycosis is a rare, invasive, and opportunistic fungal infection that occurs in the setting of neutropenia, immune deficiency, solid-organ transplant, and iron overload. The gastrointestinal system is a rare site of mucormycosis, and gastrointestinal mucormycosis is associated with high mortality and accounts for 4-7% of all cases. CASE REPORT We present the case of a 64-year-old hypertensive man with transfusion-dependent myelodysplastic syndrome who underwent renal transplant surgery 11 years ago. He also was taking maintenance Deferasirox for iron overload. He presented with a 2-day history of right lower-quadrant abdominal pain, nausea, vomiting, and non-bloody diarrhea. An abdominal examination revealed guarding and a 5×6 cm mass in the right iliac fossa. A CT scan of the abdomen showed signs of perforation of a cecal mass. As the patient was unstable, emergency right hemicolectomy and end ileostomy were performed. After the surgery, the patient was moved to the Intensive Care Unit (ICU) and a broad-spectrum antibiotic was administered. Histopathological examination results received on postoperative day 5 showed broad pauciseptate hyphae with substantial blood-vessel infiltration, suggestive of mucormycosis. Amphotericin B was started; however, on the same day, his condition deteriorated and he was moved back to the ICU. Despite maximum cardiorespiratory support, he had multiorgan failure and died. CONCLUSIONS Gastrointestinal mucormycosis presentation is non-specific, the diagnosis is often made late or is missed, and mortality remains high. High clinical suspicion, early diagnosis, and combined antifungal and surgical treatment is the best way to reduce mortality and improve survival.BACKGROUND Achilles tendinopathy commonly occurs in specific regions of the tendon, and Achilles tendon stiffness can be related to local pathological changes in the tendon. The MyotonPRO is a new handheld device that conveniently assesses stiffness of muscles and tendons. This study aimed to 1) evaluate the intra- and inter-rater reliability of stiffness measurements of the Achilles tendon at different ankle positions, 2) investigate the modulation of stiffness at different ankle joint angles, and 3) examine the differences between 2 regions of Achilles tendon stiffness. MATERIAL AND METHODS Thirty healthy young adults (15 men and 15 women) participated in this study. The regional Achilles tendon stiffness at 0 cm (AT-0) and 6 cm (AT-6) above the tendon insertion were evaluated by the MyotonPRO in the neutral position and 10° dorsiflexion of the ankle joint. Measurements of stiffness were taken by 2 raters on the first day and 5 days later. The stiffness data were compared by repeated measures analysis of variance (ANOVA). RESULTS The intra- and inter-rater reliability of stiffness measurements at AT-0 and AT-6 for each ankle position were good (all intraclass correlation coefficients >0.84). A significant modulation of Achilles tendon stiffness was obtained at different ankle joint angles (P less then 0.05). Stiffness at AT-0 was higher than at AT-6 (P less then 0.05) in both positions. CONCLUSIONS These results suggest the MyotonPRO reliably assessed Achilles tendon stiffness and monitors its modulation, and tendon stiffness increased with ankle dorsiflexion. Stiffness was also nonuniform along the length of the tendon.As in many Western countries, deep brain stimulation (DBS) is already being used daily in Japan to clinically treat neurological diseases such as Parkinson's disease, essential tremor, and dystonia. Additionally, in both Europe and the United States, numerous case reports as well as multicenter randomized controlled trials have examined its use for treatment-refractory mental illnesses such as obsessive compulsive disorder (OCD) and major depressive disorder. Based on a number of the reports, the European Union (EU) and the USA Food and Drug Administration (FDA) granted limited approval of DBS for treatment-resistant OCD in 2009. Furthermore, a systematic review and meta-analysis in 2015 showed that DBS therapy for patients with treatment-resistant OCD had efficacy and was safe. Unlike the EU and the USA, DBS is not used to treat OCD or other psychiatric disorders in Japan, even though people with treatment-resistant OCD and their physicians and families urgently need additional treatments. This situation results from the "Resolution of total denial for psychosurgery," which the Japanese Society of Psychiatry and Neurology adopted in 1975.
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