Complex intrinsic abnormalities in osteoblast lineage cells of X-linked hypophosphatemia: Analysis of human iPS cell models generated by CRISPR/Cas9-mediated gene ablation.

X-linked hypophosphatemia (XLH) is caused by inactivating variants of the phosphate regulating endopeptidase homolog X-linked (PHEX) gene. Although the overproduction of fibroblast growth factor 23 (FGF23) is responsible for hypophosphatemia and impaired vitamin D metabolism, the pathogenesis of XLH remains unclear. We herein generated PHEX-knockout (KO) human induced pluripotent stem (iPS) cells by applying CRISPR/Cas9-mediated gene ablation to an iPS clone derived from a healthy male, and analyzed PHEX-KO iPS cells with deletions extending from exons 1 to 3 and frameshifts by inducing them to differentiate into the osteoblast lineage.

Growth-related skeletal changes and alterations in phosphate metabolism.

Serum inorganic phosphate (Pi) levels are higher in children than in adults; however, the underlying mechanisms remain unclear. Therefore, we herein attempted to elucidate the mechanisms altering Pi metabolism from youth to adulthood using 4-week-old (young) and 12-week-old (adult) mice. Despite higher serum Pi levels, serum fibroblast growth factor 23 (FGF23) levels were lower in young mice, and the amount of FGF23 in bone tended to increase from youth to adulthood.

Clonal osteoblastic cell lines with CRISPR/Cas9-mediated ablation of Pit1 or Pit2 show enhanced mineralization despite reduced osteogenic gene expression.

Multiple actions of extracellular Pi on the skeletal cells are likely to be partly mediated by type III sodium/phosphate (Na/Pi) cotransporters Pit1 and Pit2, although the details are not fully understood. In the current study, to determine the roles of Pit1 and Pit2 in osteoblasts, we generated Pit1-knockout (KO) and Pit2-KO osteoblastic cells by applying CRISPR/Cas9 genome editing to an osteoblastic cell line MC3T3-E1 subclone 4. The extracellular Pi level was increased in the Pit1-KO and Pit2-KO clones due to the reduced Pi uptake.

Development of a brief screening interview for adjustment disorders and major depression in patients with cancer.

Background: Adjustment disorders and major depression are common psychiatric disorders in patients with cancer and have a serious impact on quality of life. The problem in clinical oncology settings is underrecognition of these disorders; as a result, screening is recommended to detect them. The goal of the current study was to develop a new, brief screening tool for adjustment disorders and major depression and to compare its performance with that of existing screening methods.

Somatic symptoms for diagnosing major depression in cancer patients.

Diagnosing depression in cancer patients has been challenging because the diagnostic criteria include somatic symptoms frequently attributed to the cancer itself or its treatment. However, few studies have explored how to appropriately deal with individual somatic symptoms. The authors used data from 220 cancer patients with major depression to examine the intercorrelations among the DSM-IV somatic and nonsomatic symptom criteria as well as whether the presence of an individual somatic symptom could discriminate the severity of major depression.

Psychiatric evaluation of competency in cancer patients.

This study was conducted to investigate the profile of patients referred for psychiatric evaluation of competency among patients with cancer. Among the 1721 referred cancer patients, 43 (2.5%) were referred for competency evaluation.

Psychological distress of family members with cancer patients in Japan.

Background: There were no previous studies in Japan on the psychological distress of members of families with cancer patients which focussed on the disclosure of the diagnosis of cancer. This study was designed to investigate factors that may have an effect on the psychological distress of family members.

Methods: The subjects were 95 members of families of cancer patients in the surgical ward; one member was recruited from each patient's family.

Clinical experience of the pharmacological treatment algorithm for major depression in advanced cancer patients: preliminary study.

Introduction: Treatment of major depression in advanced cancer patients is often difficult because of their special characteristics.

Method: The authors developed a treatment algorithm for major depression in advanced cancer patients and report on their clinical experience using it. The applicability, tolerability, and clinical efficacy of the algorithm were evaluated in 95 advanced cancer patients with major depression.