Deep CO Observations and the CO-to-H_2 Conversion Factor in DDO 154, a Low Metallicity Dwarf Irregular Galaxy

We present a deep spectroscopic search for CO emission in the dwarf irregular galaxy DDO154, which has an Oxygen abundance of only 1/20 the solar value. The observations were conducted in order to constrain the CO-to-$\mathrm{H_2}$ conversion factor at low metallicity. No CO was detected, however, despite being one of the sensitive observations done towards galaxies of this type. We succeed in putting a strong lower limit on the conversion factor, at least 10 times the Galactic value. Our result supports previous studies which argue for a high conversion factor at low metallicity.Comment: 11 pages, 4 figures. Accepted for publication in PAS

A discrepancy between clinical course and magnetic resonance imaging in a case of non-herpetic acute limbic encephalitis

We report the case of a 64-year old man who presented memory disturbance, low-grade fever, weight loss, and bilateral hand tremors for three months. He was diagnosed with non-herpetic acute limbic encephalitis (NHALE). Follow-up magnetic resonance imaging (MRI) revealed new lesions after symptomatic improvement following steroid pulse therapy. This may indicate that there is a time lag between the disturbance or recovery of neurons and astrocytes. Thus, other lesions might occasionally appear during convalescence in patients with NHALE, even if only minimal lesions were found on the initial MRI

Negatively charged low-density lipoprotein is associated with atherogenic risk in hypertensive patients

Negatively charged low-density lipoprotein (LDL), generated via multiple processes such as oxidation, acetylation, or glycosylation, plays a key role in the initiation and progression of atherosclerosis and related diseases. Anion-exchange high-performance liquid chromatography (AE-HPLC) can subfractionate LDL into LDL-1, LDL-2, and LDL-3 based on LDL particle charge, but the clinical significance of LDL subfractions has not yet been elucidated. The aim of this study was to determine the clinical significance of these fractions with particular regard to atherogenic risk in hypertensive patients. Ninety-eight patients with essential hypertension (age 67.0 ± 10.7 years; 54 males) were enrolled in the present study. The relationships between LDL subfractions and atherogenic risk factors, including lipid profiles, blood pressure and plasma 8-isoprostane as a marker of oxidative stress, were examined. LDL-1 levels were significantly and negatively correlated with body mass index (r = -0.384, p < 0.001), systolic blood pressure (r = -0.457, p < 0.001), non-high-density lipoprotein cholesterol levels (r = -0.457, p < 0.001) and 8-isoprostane levels (r = -0.415, p < 0.001). LDL-3, which is the most negatively charged fraction of total LDL, was significantly and positively correlated with these parameters (r = 0.267, 0.481, 0.357, and 0.337, respectively). LDL-1 levels were significantly lower (p < 0.001), and LDL-2 and LDL-3 levels were significantly higher (each p < 0.001) in patients with poorly controlled hypertension than in patients with well-controlled hypertension. In addition, an increase in the total number of traditional risk factors at time of study participation, but not previous diagnosis, was associated with a decrease in LDL-1 levels and increases in LDL-2 and LDL-3 levels. These data suggest that LDL subfractions are associated with multiple atherogenic risk factors and that treatment to modify these risk factors could result in Negatively charged low-density lipoprotein (LDL), generated via multiple processes such as oxidation, acetylation, or glycosylation, plays a key role in the initiation and progression of atherosclerosis and related diseases. Anion-exchange high-performance liquid chromatography (AE-HPLC) can subfractionate LDL into LDL-1, LDL-2, and LDL-3 based on LDL particle charge, but the clinical significance of LDL subfractions has not yet been elucidated. The aim of this study was to determine the clinical significance of these fractions with particular regard to atherogenic risk in hypertensive patients. Ninety-eight patients with essential hypertension (age 67.0 ± 10.7 years; 54 males) were enrolled in the present study. The relationships between LDL subfractions and atherogenic risk factors, including lipid profiles, blood pressure and plasma 8-isoprostane as a marker of oxidative stress, were examined. LDL-1 levels were significantly and negatively correlated with body mass index (r = −0.384, p < 0.001), systolic blood pressure (r = −0.457, p < 0.001), non-high-density lipoprotein cholesterol levels (r = −0.457, p < 0.001) and 8-isoprostane levels (r = −0.415, p < 0.001). LDL-3, which is the most negatively charged fraction of total LDL, was significantly and positively correlated with these parameters (r = 0.267, 0.481, 0.357, and 0.337, respectively). LDL-1 levels were significantly lower (p < 0.001), and LDL-2 and LDL-3 levels were significantly higher (each p < 0.001) in patients with poorly controlled hypertension than in patients with well-controlled hypertension. In addition, an increase in the total number of traditional risk factors at time of study participation, but not previous diagnosis, was associated with a decrease in LDL-1 levels and increases in LDL-2 and LDL-3 levels. These data suggest that LDL subfractions are associated with multiple atherogenic risk factors and that treatment to modify these risk factors could result in changes in LDL subfraction levels. In conclusion, LDL subfractions isolated by AE-HPLC may represent a marker of atherogenic risk in patients with hypertension

Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice

Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)–like 2 (Nrf2) alleviates obesity and insulin resistance in mice; however, Nrf2 inducers are not clinically available owing to safety concerns. Thus, we examined whether dietary glucoraphanin, a stable precursor of the Nrf2 inducer sulforaphane, ameliorates systemic energy balance, chronic inflammation, insulin resistance, and NAFLD in high-fat diet (HFD)–fed mice. Glucoraphanin supplementation attenuated weight gain, decreased hepatic steatosis, and improved glucose tolerance and insulin sensitivity in HFD-fed wild-type mice but not in HFD-fed Nrf2 knockout mice. Compared with vehicle-treated controls, glucoraphanin-treated HFD-fed mice had lower plasma lipopolysaccharide levels and decreased relative abundance of the gram-negative bacteria family Desulfovibrionaceae in their gut microbiomes. In HFD-fed mice, glucoraphanin increased energy expenditure and the protein expression of uncoupling protein 1 (Ucp1) in inguinal and epididymal adipose depots. Additionally, in this group, glucoraphanin attenuated hepatic lipogenic gene expression, lipid peroxidation, classically activated M1-like macrophage accumulation, and inflammatory signaling pathways. By promoting fat browning, limiting metabolic endotoxemia-related chronic inflammation, and modulating redox stress, glucoraphanin may mitigate obesity, insulin resistance, and NAFLD

Serum markers in interstitial pneumonia with and without Pneumocystis jirovecii colonization: a prospective study

<p>Abstract</p> <p>Background</p> <p>In patients with chronic respiratory disease, <it>Pneumocystis jirovecii (P. jirovecii) </it>colonization is observed, and may influence disease progression and systemic inflammation. <it>Pneumocystis </it>pneumonia causes interstitial changes, so making a diagnosis of PCP in patients who have interstitial pneumonia (IP) with <it>P. jirovecii </it>colonization is sometimes difficult based on radiography.</p> <p>Methods</p> <p>This study investigated the prevalence of <it>P. jirovecii </it>colonization in IP patients and assessed pulmonary injury due to <it>P. jirovecii </it>colonization by measurement of serum markers (KL-6, SP-A, SP-D, and (1→3) β-D-glucan (β-D-glucan)) and the peripheral lymphocyte counts, prospectively. A total of 75 patients with idiopathic pulmonary fibrosis (n = 29), collagen vascular-related interstitial pneumonia (n = 19), chronic bronchitis or pneumonia (n = 20), and <it>Pneumocystis </it>pneumonia (n = 7) were enrolled in this prospective study. <it>P. jirovecii </it>DNA was detected in sputum samples, while serum markers and the lymphocyte count were measured in the peripheral blood.</p> <p>Results</p> <p>IP patients (idiopathic pulmonary fibrosis and collagen vascular-related IP) who received oral corticosteroids had a high prevalence of <it>P. jirovecii </it>colonization (23.3%). In IP patients, oral corticosteroid therapy was a significant risk factor for <it>P. jirovecii </it>colonization (<it>P </it>< 0.05). Serum markers did not show differences between IP patients with and without <it>P. jirovecii </it>colonization. The β-D-glucan level and lymphocyte count differed between patients with <it>Pneumocystis </it>pneumonia or <it>P. jirovecii </it>colonization.</p> <p>Conclusion</p> <p>Serum levels of KL-6, SP-A, SP-D, and β-D-glucan were not useful for detecting <it>P. jirovecii </it>colonization in IP patients. However, the serum β-D-glucan level and lymphocyte count were useful for distinguishing <it>P. jirovecii </it>colonization from <it>pneumocystis </it>pneumonia in IP patients.</p

Carbon-Ion Beam Irradiation Kills X-Ray-Resistant p53-Null Cancer Cells by Inducing Mitotic Catastrophe

Background and Purpose: To understand the mechanisms involved in the strong killing effect of carbon-ion beam irradiation on cancer cells with TP53 tumor suppressor gene deficiencies.Copyright:Materials and Methods: DNA damage responses after carbon-ion beam or X-ray irradiation in isogenic HCT116 colorectal cancer cell lines with and without TP53 (p53+/ + and p53-/-, respectively) were analyzed as follows: cell survival by clonogenic assay, cell death modes by morphologic observation of DAPI-stained nuclei, DNA doublestrand breaks (DSBs) by immunostaining of phosphorylated H2AX (γH2AX), and cell cycle by flow cytometry and immunostaining of Ser10-phosphorylated histone H3.Results: The p53-/- cells were more resistant than the p53+/+ cells to X-ray irradiation, while the sensitivities of the p53+/+ and p53-/- cells to carbon-ion beam irradiation were comparable. X-ray and carbon-ion beam irradiations predominantly induced apoptosis of the p53+/+ cells but not the p53-/- cells. In the p53-/- cells, carbon-ion beam irradiation, but not X-ray irradiation, markedly induced mitotic catastrophe that was associated with premature mitotic entry with harboring longretained DSBs at 24 h post-irradiation.Conclusions: Efficient induction of mitotic catastrophe in apoptosis-resistant p53- deficient cells implies a strong cancer cell-killing effect of carbon-ion beam irradiation that is independent of the p53 status, suggesting its biological advantage over X-ray treatment

Administration of tranexamic acid to patients undergoing surgery for adolescent idiopathic scoliosis evokes pain and increases the infusion rate of remifentanil during the surgery

<div><p>Background</p><p>We recently reported that tranexamic acid (TXA) evokes pain in rats by inhibiting γ-aminobutyric acid and glycine receptors on neurons in the spinal dorsal horn. Although TXA is commonly used to reduce perioperative blood loss during various surgeries, its potential to induce intraoperative nociception, thereby increasing the need for more analgesics during surgery, has not been investigated. Therefore, this study aimed to investigate whether TXA evokes pain and increases the need for a higher infusion rate of remifentanil in patients undergoing surgery for adolescent idiopathic scoliosis (AIS).</p><p>Methods</p><p>Data were collected from patients with AIS who underwent posterior spinal fusion surgery from January 2008 to December 2015. All surgical procedures were performed under total intravenous anesthesia with propofol and remifentanil, by the same team of orthopedic surgeons and anesthesiologists at a single institution. Patients in the TXA group were administered TXA (loading and maintenance doses, 1000 mg and 100 mg/h) whereas those in the control group were not. Our primary outcome was the infusion rate of the intraoperative opioid analgesic remifentanil.</p><p>Results</p><p>The final analysis was based on data collected from 33 and 30 patients in the control and TXA groups, respectively. No differences were observed in the demographic data or the hemodynamic parameters between the two groups of patients. In the TXA group, the durations of surgery and anesthesia were shorter, intravascular fluid volume and total blood loss were lower, and the doses of fentanyl and ketamine administered were higher than they were in the control group (<i>P</i> < 0.05 for all). The mean infusion rate of intraoperative remifentanil was significantly higher in the TXA group than in the control group (control group: 0.23 ± 0.04 μg/kg/min; TXA group: 0.28 ± 0.12 μg/kg/min; <i>P</i> = 0.014).</p><p>Conclusions</p><p>Patients who received TXA during the AIS surgery required a higher infusion rate of remifentanil, indicating that TXA evoked pain during the surgery.</p></div

Surgical data of patients in each group.

<p>Surgical data of patients in each group.</p

Demographic data of the patients in each group.

<p>Demographic data of the patients in each group.</p