Accuracy and reliability of continuous blood glucose monitoring during pediatric cardiopulmonary bypass

Journal of Artificial Organs - The purpose of this study was to assess the accuracy and reliability of a continuous blood glucose monitoring system (artificial endocrine pancreas; STG-55, Nikkiso,...     

Clinical and molecular features of treatment‐related neuroendocrine prostate cancer

Treatment‐related neuroendocrine prostate cancer is a lethal form of prostate cancer that emerges in the later stages of castration‐resistant prostate cancer treatment. Treatment‐related neuroendocrine prostate cancer transdifferentiates from adenocarcinoma as an adaptive response to androgen receptor pathway inhibition. The incidence of treatment‐related neuroendocrine prostate cancer has been rising due to the increasing use of potent androgen receptor pathway inhibitors. Typically, treatment‐related neuroendocrine prostate cancer is characterized by either low or absent androgen receptor expression, small cell carcinoma morphology and expression of neuroendocrine markers. Clinically, it manifests with predominantly visceral or lytic bone metastases, bulky tumor masses, low prostate‐specific antigen levels or a short response duration to androgen deprivation therapy. Furthermore, although the tumor initially responds to platinum‐based chemotherapy, the duration of the response is short. Based on the poor prognosis, it is imperative to identify novel molecular targets for treatment‐related neuroendocrine prostate cancer. Recent advances in genomic and molecular research, supported by novel in vivo models, have identified some of the key molecular characteristics of treatment‐related neuroendocrine prostate cancer. The gain of MYCN and AURKA oncogenes, along with the loss of tumor suppressor genes TP53 and RB1 are key genomic alterations associated with treatment‐related neuroendocrine prostate cancer. Androgen receptor repressed genes, such as BRN2 and PEG10, are also necessary for treatment‐related neuroendocrine prostate cancer. These genetic changes converge on pathways upregulating genes, such as SOX2 and EZH2, that facilitate lineage plasticity and neuroendocrine differentiation. As a result, on potent androgen receptor pathway inhibition, castration‐resistant prostate cancer transdifferentiates to treatment‐related neuroendocrine prostate cancer in a clonally divergent manner. Further understanding of the disease biology is required to develop novel drugs and biomarkers that would help treat this aggressive prostate cancer variant.     

Echocardiographic changes in diastolic filling and stroke volume during postural alterations and ankle exercise in a patient with congenital defect of the pericardium

Journal of Echocardiography -     

Malaria parasites giving rise to recrudescence in vitro

Recrudescences were simulated in vitro with drug treatment to examine how drug-sensitive parasites survive the treatment. Various numbers of cultured parasites were treated with lethal doses of pyrimethamine or mefloquine for various lengths of time. Recrudescences were observed in parasite populations with larger initial numbers of parasites when the treatment duration was prolonged. Equal numbers of parasitized erythrocytes were treated with various concentrations of pyrimethamine or mefloquine. There was no clear linear relationship between the incidence of recrudescence and the drug concentration. Parasites that had recrudesced were continuously allowed to recrudesce in the succeeding recrudescence experiments. Both the duration from the cessation of treatment to the time at which the recrudescent parasitemia level reached 1% and the growth rate of recrudescent parasites were equal among these recrudescences. The recrudescent parasites in these experiments were as sensitive to the drugs as the parasites tested before treatment were. These results suggest that a parasite culture may contain parasites in some phases that are not killed by drug for up to 10 days, which explains the recrudescences that occur even after treatment.     

A 14-year-old girl with hyperekplexia having GLRB mutations

Hyperekplexia manifests as generalized stiffness and an excessive startle reflex to stimuli. It starts in the neonatal period and is transmitted in many cases via autosomal dominant inheritance. The etiology is an abnormality of the glycinergic neurotransmission system that is involved in inhibitory neurotransmission. Aberrations of five genes related to this neurotransmission system have been identified. The patient was a 14-year-old girl with mild mental retardation. None of her family members had a neuromuscular disease. An excessive startle reflex and generalized stiffness were noted immediately after birth and she was diagnosed with epilepsy because epileptic discharges were observed. However, the disease was resistant to various antiepileptic drugs and the startle responses persisted. GLRB gene mutations (R50X/Q216fsx222) were identified, after which the patient was diagnosed with hyperekplexia. The startle reflex improved when clonazepam treatment was initiated. When patients have a persistent startle reflex, it is necessary to consider hyperekplexia, even if epileptic discharges are observed. Only four cases with GLRB mutations, including the present patient, have been reported. To make a definite diagnosis of hyperekplexia, it may be useful to screen for genes that are involved in the glycinergic neurotransmission system.