Alcohol's harm to others in Japan: Different rates for different relationships to the drinker in a 2018 national survey.

INTRODUCTION: No study in Japan has investigated alcohol's harm to others (AHTO). Therefore, this study aimed to reveal the situation of AHTO in Japan and examine the factors associated with it based on the relationship with the drinker. METHODS: A cross-sectional population-based survey was performed in 2018 with 2121 men and 2507 women. Respondents were asked questions about factors such as verbal or physical aggression, being forced to drink alcohol, sexual harassment and their relationship with the drinker. Binomial logistic regression was performed to quantify the associations of AHTO with participants' socio-demographic status and drinking patterns. RESULTS: The lifetime experience of AHTO was 24.7% for men and 19.3% for women. AHTO from the father and co-workers were the most common in and outside the home, respectively. The frequency of AHTO from the spouse or co-workers showed no significant difference for abstainers and drinkers. However, AHTO from the father was more commonly reported among drinkers and those with Alcohol Use Disorders Identification Test scores ≥8 points than abstainers. Of those who experienced AHTO, 24.5% of men and 27.6% of women, and 6.1% of men and 12.9% of women were profoundly affected by it in and outside the home, respectively. DISCUSSION AND CONCLUSIONS: One in five Japanese residents experienced AHTO in their life, and the characteristics associated with AHTO differed according to the affected individual's relationship with the drinker. Continued monitoring of AHTO and measures aimed at reducing alcohol-related harm that include AHTO should be promoted.

Trends and differences in alcohol-related mortality rates by gender and by prefectures in Japan between 1995 and 2016.

BACKGROUND: This study aimed to identify increases in 100 % alcohol-related death (ARD) and any differences among prefectures between 1995-2016. METHODS: Data from the national death registry on 100 % ARDs between 1995-2016 were extracted. Age-standardized mortality rate (ASMR) of 100 % ARD by year, gender, and gender ratio were calculated. After dividing the period into 1995-2005 and 2006-2016, the ASMRs of 100 % ARDs were calculated by prefecture. Additionally, based on geographical area, municipality size, or annual alcohol sales per adult in each prefecture, prefectures were divided into groups and analysed. RESULTS: In total, 95,455 deaths were caused by 100 % ARD from 1995-2016. Men's ASMRs of 100 % ARD markedly increased from 4.0 per 100,000 in 1995 to 5.2 between 2010 and 2013, and gradually declined to 5.0 in 2016. Women's ASMRs increased steadily from 0.3 in 1995 to 0.8 in 2016. The gender ratio of ASMRs decreased from 13.3 in 1995 to 6.3 in 2016. The ASMR of one prefecture, which had reduced alcohol tax rates, was higher for both genders. Both men's and women's ASMRs were higher in the prefectures that had higher alcohol sales (6.3 [5.0-7.7] and 0.8 [0.6-1.1], respectively) compared to the prefectures that had lower alcohol sales (4.3 [4.0-4.7] p < 0.001 and 0.6 [0.5-0.6] p = 0.045, respectively). CONCLUSIONS: The ASMR of 100 % ARD remained high for men and increased for women, and prefecture-level higher alcohol sales and lower tax rates correlated with the higher mortality rate. Increasing prices and taxes and reducing alcohol sales may contribute to a decrease in alcohol-related mortality.

Stagnant forearc mantle wedge inferred from mapping of shear-wave anisotropy using S-net seafloor seismometers.

Shear-wave anisotropy in Earth's mantle helps constrain the lattice-preferred orientation of anisotropic minerals due to viscous flow. Previous studies at the Japan Trench subduction zone using land-based seismic networks identified strong anisotropy in the mantle wedge, reflecting viscous flow induced by the subducting slab. Here we map anisotropy in the previously uninvestigated offshore region by analyzing shear waves from interplate earthquakes that are recorded by a new seafloor network (the S-net). The newly detected anisotropy is not in the mantle wedge but only in the overlying crust (∼0.1 s time delay and trench-parallel fast direction). The distinct lack of anisotropy indicates that the forearc mantle wedge offshore is decoupled from the slab and does not participate in the viscous flow, in sharp contrast with the rest of the mantle wedge. A stagnant forearc mantle wedge provides a stable and cold tectonic environment that is important for the petrological evolution and earthquake processes of subduction zones.

Successful endoscopic stent placement as a bridge to surgery for colonic obstruction induced by bevacizumab-based chemotherapy.

The use of a self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) for obstructive colorectal cancer is known to be effective. However, whether the use of a SEMS as a BTS for obstruction induced by effective chemotherapy (CTx) is useful is unknown. We present the case of a 54-year-old female patient with colorectal cancer who underwent SEMS placement as a BTS for colorectal obstruction induced by bevacizumab-based CTx. The patient was diagnosed as having transverse colon cancer with multiple liver metastases invading the inferior vena cava. Bevacizumab-based CTx was started; however, although it was effective, colonic obstruction occurred at the primary site after 31 months. A SEMS was placed as a BTS, and surgical resection of the primary lesion was performed after cessation of bevacizumab. However, the liver metastases remained unresectable. CTx was restarted after surgery, and 48-month survival was achieved. This case shows that SEMS placement as a BTS for colorectal obstruction induced by a good response to bevacizumab-based CTx was safe and beneficial. With the development of CTx and molecular-targeted agents, the frequency of colorectal obstruction associated with effective CTx is expected to increase. SEMS placement as a BTS might be one of the treatment options.

Successful treatment of severe rhesus D-incompatible pregnancy with repeated double-filtration plasmapheresis.

Fetal anemia is caused by Rhesus (RhD) sensitization as a result of RhD incompatibility during pregnancy. The severe form of this disease can cause hydrops fetalis leading to intrauterine death. We experienced a highly sensitized 39-year-old woman with B Rh-negative blood. She had a history of three induced abortions and experienced perinatal death associated with hydrops fetalis. During the pregnancy prior to her most recent one, she was treated with double-filtration plasmapheresis (DFPP), high dose γ-globulin and intrauterine fetal blood transfusion (IUT). For her most recent pregnancy, we performed only weekly or fortnightly DFPP from 13 weeks until delivery. Anti-D antibody titer was maintained between 32 and 256 without any signs of fetal anemia. IUT was not required at any stage of the pregnancy. No adverse events were observed. She successfully delivered a healthy male infant weighing 2,289 g by Cesarean section at 35 weeks. Repeated DFPP may be an effective and safe strategy to reduce antibody titers in highly sensitized women with RhD-incompatible pregnancy, avoiding the need for IUT.

Nrf2- and ATF4-dependent upregulation of xCT modulates the sensitivity of T24 bladder carcinoma cells to proteasome inhibition.

The ubiquitin-proteasome pathway degrades ubiquitinated proteins to remove damaged or misfolded protein and thus plays an important role in the maintenance of many important cellular processes. Because the pathway is also crucial for tumor cell growth and survival, proteasome inhibition by specific inhibitors exhibits potent antitumor effects in many cancer cells. xCT, a subunit of the cystine antiporter system xc (-), plays an important role in cellular cysteine and glutathione homeostasis. Several recent reports have revealed that xCT is involved in cancer cell survival; however, it was unknown whether xCT affects the cytotoxic effects of proteasome inhibitors. In this study, we found that two stress-inducible transcription factors, Nrf2 and ATF4, were upregulated by proteasome inhibition and cooperatively enhance human xCT gene expression upon proteasome inhibition. In addition, we demonstrated that the knockdown of xCT by small interfering RNA (siRNA) or pharmacological inhibition of xCT by sulfasalazine (SASP) or (S)-4-carboxyphenylglycine (CPG) significantly increased the sensitivity of T24 cells to proteasome inhibition. These results suggest that the simultaneous inhibition of both the proteasome and xCT could have therapeutic benefits in the treatment of bladder tumors.

Rhythmic arm swing enhances long latency facilitatory effect of transcranial magnetic stimulation on soleus motoneuron pool excitability.

The purpose of this study was to investigate whether rhythmic arm swing modulates the long latency effect of transcranial magnetic stimulation (TMS) on soleus motoneuron pool excitability. Ten healthy humans rhythmically swung the left arm back and forth in a sitting position. The soleus H-reflex was evoked when the arm was in the backward swing phase. Conditioning TMS was delivered over the motor cortex 8 ms before the soleus H-reflex was evoked. The soleus H-reflex amplitude in both legs was depressed by the rhythmic arm swing. In contrast, rhythmic arm swing enhanced the facilitatory effect of conditioning TMS over the motor cortex contralateral to the arm swing side on the soleus H-reflex ipsilateral to the arm swing side. This finding indicates that rhythmic arm swing enhances some polysynaptic facilitatory pathways from the motor cortex contralateral to the arm swing side to the soleus motoneuron pool ipsilateral to the arm swing side.

Peak spreading in linear gradient elution chromatography with a thin monolithic disk.

The peak spreading of DNAs of various sizes [12-mer, 20-mer, 50-mer and 95-mer poly(T)] in linear gradient elution (LGE) chromatography with a thin monolithic disk was investigated by using our method developed for determining HETP in LGE. Electrostatic interaction-based chromatography mode (ion-exchange chromatography, IEC) was used. Polymer-based monolithic disks of two different sizes (12 mm diameter, 3mm thickness and 0.34 mL; 5.2 mm diameter, 4.95 mm thickness and 0.105 mL) having anion-exchange groups were employed. For comparison, a 15-µm porous bead IEC column (Resource Q, 6.4mm diameter, 30 mm height and 0.97 mL) was also used. The peak width did not change with the flow velocity for the monolithic disks where as it became wider with increasing velocity. For the monolithic disks the peak width normalized with the column bed volume was well-correlated with the distribution coefficient at the peak position K(R). HETP values were constant (ca. 0.003-0.005 cm) when K(R)>5. Much higher HETP values which are flow-rate dependent were obtained for the porous bead chromatography. It is possible to obtain 50-100 plates for the 3mm monolithic disk. This results in very sharp elution peaks (standard deviation/bed volume=0.15) even for stepwise elution chromatography, where the peak width is similar to that for LGE of a very steep gradient slope.

New mu-opioid receptor agonists with phenoxyacetic acid moiety.

New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of delta- and kappa-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.