Defibrillator Shocks and Their Impact on Objective and Subjective Patient Outcomes: Results from the Painfree SST Clinical Trial

BACKGROUND: The impact of ICD shock on device-measured activity and patient reported outcomes is unknown. OBJECTIVE: The purpose of this study was to analyze the acute and long-term effects of ICD shock on objective behavioral data (i.e., device-based physical activity) and subjective patient reported outcomes (e.g., quality of life and shock anxiety). METHODS: The PainFree SST clinical trial included 2,770 patients with a single or dual-chamber ICD, or cardiac resynchronization defibrillator (CRT-D) who were followed for 22 ± 9 months. Participants completed measures of quality of life (EuroQol 5-D [EQ5D]) and shock anxiety (Florida Shock Anxiety Scale [FSAS]) at baseline, bi-annual visits, and monthly for 6 months following an ICD shock. Daily physical activity data were obtained from a built-in device accelerometer. RESULTS: Average daily activity was 185.3 ± 119.4 minutes/day. Activity was significantly reduced after an ICD shock (p<0.0001) and recovered to a normal level after approximately 90 days. ICD shock was also associated with decreased quality of life (EQ5D Health Score) and increased EQ5D anxiety scores, but it did not impact mobility, self-care, activity, or pain. Similarly, shock anxiety (FSAS) increased in shocked patients and remained significantly elevated at 24 months, regardless of appropriate or inappropriate shock delivery. CONCLUSIONS: ICD shocks have a long-lasting, adverse impact on both objective, device-measured physical activity and subjective patient reported outcomes of quality of life and shock anxiety. Successful management of ICD patients requires attention to clinically relevant behavioral and psychological outcomes to expedite recovery and return to activities of daily living

Clinical significance of disease-specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma

Recent sequencing studies demonstrated the MYD88 L265P mutation in more than 70% of primary central nervous system lymphomas (PCNSL), and the clinical significance of this mutation has been proposed as diagnostic and prognostic markers in PCNSL. In contrast, mutational analyses using cell-free DNAs have been reported in a variety of systemic lymphomas. To investigate how sensitively the MYD88 L265P mutation can be identified in cell-free DNA from PCNSL patients, we carried out droplet digital PCR (ddPCR) and targeted deep sequencing (TDS) in 14 consecutive PCNSL patients from whom paired tumor-derived DNA and cell-free DNA was available at diagnosis. The MYD88 L265P mutation was found in tumor-derived DNA from all 14 patients (14/14, 100%). In contrast, among 14 cell-free DNAs evaluated by ddPCR (14/14) and TDS (13/14), the MYD88 L265P mutation was detected in eight out of 14 (ddPCR) and in 0 out of 13 (TDS) samples, implying dependence on the detection method. After chemotherapy, the MYD88 L265P mutation in cell-free DNAs was traced in five patients; unexpectedly, the mutations disappeared after chemotherapy was given, and they remained undetectable in all patients. These observations suggest that ddPCR can sensitively detect the MYD88 L265P mutation in cell-free DNA and could be used as non-invasive diagnostics, but may not be applicable for monitoring minimal residual diseases in PCNSL

Genetic evidence implies that primary and relapsed tumors arise from common precursor cells in primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare subtype of lymphoma that arises within the brain or the eyes. PCNSL recurs within the central nervous system (CNS) in most relapsed cases, whereas extra- CNS relapse is experienced in rare cases. The present study aimed at identifying the presence of common precur -sor cells (CPC) for primary intra- and relapsed extra- CNS tumors, and further assess -ing the initiating events in bone marrow (BM). Targeted deep sequencing was carried out for five paired primary intra- and relapsed extra- CNS tumors of PCNSL. Two to five mutations were shared by each pair of intra- and extra- CNS tumors. In particular, MYD88 mutations, L265P in three and P258L in one, were shared by four pairs. Unique somatic mutations were observed in all five intra- CNS tumors and in four out of five extra- CNS tumors. Remarkably, IgH clones in the intra- and the extra- CNS tumors in two pairs were distinct from each other, whereas one pair of tumors shared identical monoclonalIgH rearrangement. In a cohort of 23 PCNSL patients, L265P MYD88 mutations were examined in tumor- free BM mononuclear cells (MNC) in which the PCNSL tumors had L265P MYD88 mutations. L265P MYD88 mutationswere detected by a droplet digital PCR method in nine out of 23 bone marrow mono -nuclear cells. These results suggest that intra- and extra- tumors are derived from CPC with MYD88 mutations in most PCNSL, arising either before or after IgH rear-rangement. The initiatingMYD88 mutations may occur during B- cell differentiation in BM

Hardness Distribution and Endosperm Structure on Polishing Characteristics of Brewer’s Rice Kernels

This study was designed to determine the effects of the hardness distribution and the endosperm structure on the polishing characteristics of brewer’s rice kernels. We used four brewer’s rice cultivars, Kairyo-omachi, Hattan-nishiki No. 1, Senbon-nishiki and Yamada-nishiki. The broken kernel ratios in Kairyo-omachi and Hattan-nishiki No. 1 were significantly higher than those in Senbon-nishiki and Yamada-nishiki. Vickers hardness (VH) values in white-core tissues in kernels differed among varieties, which were significantly lower in Kairyo-omachi and Hattan-nishiki No. 1. However, no varietal differences were observed in VH values in the peripheral translucent tissues surrounding the white-core tissues. The tissues along the dorsoventral axis were softer than those along the longitudinal axis of the kernels. The tissues on the ventral side were softer than those on the dorsal side. Scanning electron microscopy (SEM) observations revealed the presence of closely arranged compound starch granules and few varietal differences in the peripheral translucent tissues surrounding the white-core tissues. However, as compared with Yamada-nishiki and Senbon-nishiki, in Hattan-nishiki No. 1 and Kairyo-omachi, the starch granules were loosely packed and the airspaces between the starch granules were more numerous in the white-core tissues. A higher number of airspaces and less starch were present in the endosperm cells along the dorsoventral axis when compared with along the longitudinal axis and on the ventral side than on the dorsal side. The present study showed that polishing characteristics are closely related with the endosperm structure, which is characterized as the density of starch granules

Generalized spike-wave discharges involve a default mode network in patients with juvenile absence epilepsy : A MEG study

This study uses magnetoencephalography (MEG) to examine whether cortical regions that constitute a default mode network are involved during generalized spike-wave discharges (GSWs) in patients with juvenile absence epilepsy (JAE). We studied five JAE patients for whom MEG was recorded using a 204-channel, whole-head gradiometer system. Dynamic statistical parametric mapping (dSPM) was done to estimate the cortical source distribution of GSW. The dSPM results showed strong medial prefrontal activation in all patients, with activation in the posterior cingulate and precuneus in three of five patients simultaneously or slightly after medial prefrontal activation. Furthermore, dSPM showed that the initial activation of a GSW appears in the focal cortical regions. Cortical regions that constitute a default mode network are strongly involved in the GSW process in some patients with JAE. Results also show that focal cortical activation appears at the onset of a GSW

Preferences of young physicians at community hospitals regarding academic research training through graduate school: a cross-sectional research.

[Background] Desire to attend graduate school for academic research training following the mandatory two-year clinical internship is unknown among young Japanese physicians who work at community hospitals after their internship. The aim of this study is to determine opinions and factors regarding pursuing higher education through graduate school among young physicians who work at community hospitals after their two-year internship. [Methods] This cross-sectional survey was conducted among young physicians working at community hospitals after their two-year internship. We examined the percentage of young physicians considering higher education through graduate school, the planned timing and field of enrollment among those wanting to enroll, and reasons for not continuing their education among those with no such plans. The association between desire to enroll in graduate school and background characteristics was examined using modified least-squares regression to estimate proportion difference. [Results] Among 127 (73.2 % internal medicine specialists, median age 30 years) physicians in 33 hospitals, 71 (55.9 %) stated that they wished to enroll in graduate school. The most frequently reported timing was 7–8 years after graduation from medical school. Those who stated no desire to attend graduate school cited concerns about the quality of training or not having enough knowledge to choose an appropriate laboratory or field, among other reasons. Increased number of years since graduating medical school [adjusted proportion difference (PD) −6.0 %, 95 % confidence interval (95 % CI) −9.8 to −2.3 %], being a woman with children [adjusted PD −53.4 %, 95 % CI −87.3 to −19.5 % (vs. a man not having children)], and completing their two-year internship at both university and community hospitals [adjusted PD −40.3 %, 95 % CI −72.5 to −8.0 % (vs. internship only at community hospitals)] were associated with a reduction in desire to enroll in graduate school. [Conclusions] We identified a growing trend in desire among young physicians to attend graduate school. Attracting those young physicians who express no desire to attend graduate school, however, will require establishment of more flexible graduate school programs which address their concerns