Fatal Cytomegalovirus Pneumonia and Associated Herpes Virus Infection in a Relapsed/Refractory Multiple Myeloma Patient Treated with Bortezomib plus Dexamethasone

Multiple myeloma (MM) remains a largely incurable disease in the long term despite positive responses to first-line chemotherapy. Herein we report the case of a 68-year-old woman who died following treatment with bortezomib plus dexamethasone for refractory MM. The combination was associated with significant antitumor activity, but bacterial pneumonia/sepsis was followed by bilateral cytomegalovirus pneumonia with herpes simplex co-infection, and this was almost certainly the cause of death. Physicians need to pay careful attention when treating patients with refractory MM with bortezomib plus dexamethasone, and to be mindful that antiviral therapy may be needed in some cases

The Kiloparsec-scale Neutral Atomic Carbon Outflow in the Nearby Type-2 Seyfert Galaxy NGC 1068: Evidence for Negative AGN Feedback

Active galactic nucleus (AGN) feedback is postulated as a key mechanism for regulating star formation within galaxies. Studying the physical properties of the outflowing gas from AGN is thus crucial for understanding the co-evolution of galaxies and supermassive black holes. Here we report 55 pc resolution ALMA neutral atomic carbon [CI] $^3P_1\text{-}^3P_0$ observations toward the central 1 kpc of the nearby type-2 Seyfert galaxy NGC 1068, supplemented by 55 pc resolution CO($J=1\text{-}0$) observations. We find that [CI] emission within the central kpc is strongly enhanced by a factor of $>$5 compared to the typical [CI]/CO intensity ratio of $\sim$0.2 for nearby starburst galaxies (in units of brightness temperature). The most [CI]-enhanced gas (ratio $>$ 1) exhibits a kpc-scale elongated structure centered at the AGN that matches the known biconical ionized gas outflow entraining molecular gas in the disk. A truncated, decelerating bicone model explains well the kinematics of the elongated structure, indicating that the [CI] enhancement is predominantly driven by the interaction between the ISM in the disk and the highly inclined ionized gas outflow (which is likely driven by the radio jet). Our results strongly favor the "CO dissociation scenario" rather than the "in-situ C formation" one which prefers a perfect bicone geometry. We suggest that the high [CI]/CO intensity ratio gas in NGC 1068 directly traces ISM in the disk that is currently dissociated and entrained by the jet and the outflow, i.e., the "negative" effect of the AGN feedback.Comment: 12 pages, 5 figures, accepted for publication in The Astrophysical Journal Letter

Generation of three induced pluripotent stem cell lines from postmortem tissue derived following sudden death of a young patient with STXBP1 mutation

We established three iPSC lines from postmortem-cultured fibroblasts derived following the sudden unexpected death of an 8-year-old girl with Lennox-Gastaut syndrome, who turned out to have the R551H-mutant STXBP1 gene. These iPSC clones showed pluripotent characteristics while retaining the genotype and demonstrated trilineage differentiation capability, indicating their utility in disease-modeling studies, i.e., STXBP1-encephalopathy. This is the first report on the establishment of iPSCs from a sudden death child, suggesting the possible use of postmortem-iPSC technologies as an epoch-making approach for precise identification of the cause of sudden death

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

WDR55 Is a Nucleolar Modulator of Ribosomal RNA Synthesis, Cell Cycle Progression, and Teleost Organ Development

The thymus is a vertebrate-specific organ where T lymphocytes are generated. Genetic programs that lead to thymus development are incompletely understood. We previously screened ethylnitrosourea-induced medaka mutants for recessive defects in thymus development. Here we report that one of those mutants is caused by a missense mutation in a gene encoding the previously uncharacterized protein WDR55 carrying the tryptophan-aspartate-repeat motif. We find that WDR55 is a novel nucleolar protein involved in the production of ribosomal RNA (rRNA). Defects in WDR55 cause aberrant accumulation of rRNA intermediates and cell cycle arrest. A mutation in WDR55 in zebrafish also leads to analogous defects in thymus development, whereas WDR55-null mice are lethal before implantation. These results indicate that WDR55 is a nuclear modulator of rRNA synthesis, cell cycle progression, and embryonic organogenesis including teleost thymus development

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment

「緩和ケアを推進する看護師教育プログラム」の評価 : 修了者およびその上司への調査から

京都府立医科大学医学部看護学科京都府立医科大学附属病院看護部京都府立医科大学看護実践キャリア開発センター京都府立医科大学附属病院地域医療推進部School of Nursing, Kyoto Prefectural University of MedicineDepartment of Nursing, University Hospital Kyoto Prefectural University of MedicineKyoto Prefectural University of Medicine, Career Development Center for NursingPromotion Division of Regional Medicine, University Hospital Kyoto Prefectural University of Medicine　本研究の目的は、「緩和ケア実践看護師養成コース（以下Aコース）」「在宅緩和ケア推進看護師養成コース（以下Bコース）」を受講した修了者とその上司への調査からプログラム評価および看護実践への活用状況を指標にしてプログラムを評価することである。【方法】平成27～31年度の間に京都府立医科大学看護実践キャリア開発センターが開催する「緩和ケアを推進する看護師教育プログラム」のAコースまたはBコースを受講した修了者25名のうち、調査時点で受講時と同じ施設・病院で就労を継続している21名（Aコース14名、Bコース7名）、とその上司21名（Aコース14名、Bコース7名）を研究対象者とした。修了生の施設・病院に質問紙を郵送し、令和3年7月～8月に無記名の自記式質問紙調査を行った。調査項目は、基本属性、カリキュラムについて、教育目標について、受講内容の適切性について、学習内容の臨床での活用について、とした。なお所属する大学の医学倫理審査委員会の承認を得て実施した（ERB-E-444）。【結果】回答者は、Aコース修了者9名、Aコース上司7名、Bコース修了者5名、Bコース上司3名であった。受講した修了者の評価においては、プログラムの内容についてAコースの8割以上が、Bコースの全員が（とても・まあまあ）適切としている。自己能力の発揮状況について、Aコースは4～6割、Bコースについては4～8割ができているとしている。　上司からの評価では、両コースとも受講した講義・演習・実習が7割程度現在の看護実践に役立っていると答えた。期待される能力については両コースとも8割以上が現在の看護活動に活きていると答えた。【結論】平成27年度から開始された「緩和ケアを推進する看護師教育プログラム」に対して、受講した修了者とその上司に，研修が有用であったかを問うたところ、受講した修了者はプログラムの内容が看護の実践で活かされていると実感していることが明らかとなった。さらに、上司は、受講した修了者が研修を踏まえた看護実践ができていると評価していることが明らかになった。修了者、上司の評価からプログラムの効果を評価することができた

Intracellular pH in neurons of dorsal root ganglia.

O objetivo do trabalho foi determinar o pHi, a capacidade tamponante do citosol na ausência de CO2/HCO3- (&#946;i) de neurônios dos gânglios das raízes dorsais e investigar a expressão de trocadores Na+/H+ e sua função na regulação do pHi. O pHi foi estimado com o indicador fluorescente BCECF. A operação do trocador era quantificada na recuperação da acidose intracelular induzida experimentalmente. Na ausência do tampão CO2/HCO3- a taxa de alcalinização (k) deve-se, por hipótese, ao transporte de H+ pelo trocador. A hipótese foi confirmada pela ação de agentes farmacológicos, e.g., amiloride. Em soluções tamponadas por CO2/HCO3- as células tem pHi de 7,24 e, em soluções tamponadas com HEPES, 7,04. A &#946;i foi de 8,17 mM/pH. As células se recuperam da acidose com k médio de 0,0138 s-1. O efeito inibitório do amiloride em concentração de 1 mM deve-se ao fato dos fenótipos celulares expressarem diferentes isoformas do trocador. Segundo RT-PCR, todas as 5 isoformas do trocador são expressas e a quantidade de RNAm, avaliada por qPCR, é maior para a NHE1, seguida de NHE5.The objective here was to determine intracellular pH (pHi), cytosolic buffering power in CO2/HCO3- free medium (&#946;i) of neurons from dorsal root ganglia and to investigate the functional expression of the Na+/H+ exchangers in the regulation of pHi. pHi was estimated with fluorescence indicator BCECF. Exchanger operation was quantified during recovery from intracellular acidification induced experimentally. In CO2/HCO3- free medium the alkalinization rate (k) is due, hypothetically, H+ extrusion by the exchanger. This assumption was confirmed by action of pharmacologic agents, e.g., amiloride. In medium buffered with CO2/HCO3- cells have pHi of 7.24 and, in medium buffered with HEPES, 7.04. &#946;i calculated was 8.17 mM/pH. Cells recovery from acidosis with mean k of 0.0138 s-1. Inhibitory effect of amiloride in 1 mM concentration is due to cellular phenotypes expressing different Na+/H+ exchanger isoforms. According to RT-PCR, all the five exchanger isoforms are expressed and mRNA quantity, evaluated by qPCR, is greater to NHE1, followed by NHE5

Intracellular pH in neurons of dorsal root ganglia.

O objetivo do trabalho foi determinar o pHi, a capacidade tamponante do citosol na ausência de CO2/HCO3- (&#946;i) de neurônios dos gânglios das raízes dorsais e investigar a expressão de trocadores Na+/H+ e sua função na regulação do pHi. O pHi foi estimado com o indicador fluorescente BCECF. A operação do trocador era quantificada na recuperação da acidose intracelular induzida experimentalmente. Na ausência do tampão CO2/HCO3- a taxa de alcalinização (k) deve-se, por hipótese, ao transporte de H+ pelo trocador. A hipótese foi confirmada pela ação de agentes farmacológicos, e.g., amiloride. Em soluções tamponadas por CO2/HCO3- as células tem pHi de 7,24 e, em soluções tamponadas com HEPES, 7,04. A &#946;i foi de 8,17 mM/pH. As células se recuperam da acidose com k médio de 0,0138 s-1. O efeito inibitório do amiloride em concentração de 1 mM deve-se ao fato dos fenótipos celulares expressarem diferentes isoformas do trocador. Segundo RT-PCR, todas as 5 isoformas do trocador são expressas e a quantidade de RNAm, avaliada por qPCR, é maior para a NHE1, seguida de NHE5.The objective here was to determine intracellular pH (pHi), cytosolic buffering power in CO2/HCO3- free medium (&#946;i) of neurons from dorsal root ganglia and to investigate the functional expression of the Na+/H+ exchangers in the regulation of pHi. pHi was estimated with fluorescence indicator BCECF. Exchanger operation was quantified during recovery from intracellular acidification induced experimentally. In CO2/HCO3- free medium the alkalinization rate (k) is due, hypothetically, H+ extrusion by the exchanger. This assumption was confirmed by action of pharmacologic agents, e.g., amiloride. In medium buffered with CO2/HCO3- cells have pHi of 7.24 and, in medium buffered with HEPES, 7.04. &#946;i calculated was 8.17 mM/pH. Cells recovery from acidosis with mean k of 0.0138 s-1. Inhibitory effect of amiloride in 1 mM concentration is due to cellular phenotypes expressing different Na+/H+ exchanger isoforms. According to RT-PCR, all the five exchanger isoforms are expressed and mRNA quantity, evaluated by qPCR, is greater to NHE1, followed by NHE5