Social distancing as a public good under the COVID-19 pandemic.

OBJECTIVES: The purpose of this study is to show that social distancing is a public good under the COVID-19 pandemic. STUDY DESIGN: We apply economic theory to analyse a cross-sectional survey. METHODS: Economic theory is complemented with empirical evidence. An online survey of those aged 30-49 years in Japan (n = 2177) was conducted between April 28 and May 7. Respondents were selected by quota sampling with regard to age group, gender and prefecture of residence. Our main figure shows the proportion of people who increased/did not change/decreased social distancing, relative to the level of altruism and sensitivity to public shaming. The results of OLS and logit models are shown in Supplementary Materials. RESULTS: Social distancing is a public good under the COVID-19 pandemic for which the free-rider problem is particularly severe. Altruism and social norms are crucial factors in overcoming this problem. Using an original survey, we show that people with higher altruistic concerns and sensitivity to shaming are more likely to follow social distancing measures. CONCLUSIONS: Altruism and social norms are important for reducing the economic cost of the pandemic.

The mitochondrial calcium uniporter contributes to morphine tolerance through pCREB and CPEB1 in rat spinal cord dorsal horn.

BACKGROUND: The long-term use of opioid analgesics is limited by the development of unwanted side-effects, such as tolerance. The molecular mechanisms of morphine anti-nociceptive tolerance are still unclear. The mitochondrial calcium uniporter (MCU) is involved in painful hyperalgesia, but the role of MCU in morphine tolerance has not been uncharacterised. METHODS: Rats received intrathecal injection of morphine for 7 days to induce morphine tolerance. The mechanical withdrawal threshold was measured using von Frey filaments, and thermal latency using the hotplate test. The effects of an MCU inhibitor, antisense oligodeoxynucleotide against cyclic adenosine monophosphate response element (CRE)-binding protein (CREB) or cytoplasmic polyadenylation element-binding protein 1 (CPEB1) in morphine tolerance were examined. RESULTS: Spinal morphine tolerance was associated with an increased expression of neuronal MCU, phospho-CREB (pCREB), and CPEB1 in the spinal cord dorsal horn. MCU inhibition increased the mechanical threshold and thermal latency, and reduced the accumulation of mitochondrial calcium in morphine tolerance. Intrathecal antisense oligodeoxynucleotide against CREB or CPEB1 restored the anti-nociceptive effects of morphine compared with mismatch oligodeoxynucleotide in von Frey test and hotplate test. Chromatin immunoprecipitation with quantitative PCR assay showed that CREB knockdown reduced the interaction of pCREB with the ccdc109a gene (encoding MCU expression) promoter and decreased the MCU mRNA transcription. RNA immunoprecipitation assay suggested that CPEB1 binds to the MCU mRNA 3' untranslated region. CPEB1 knockdown decreased the expression of MCU protein. CONCLUSIONS: These findings suggest that spinal MCU is regulated by pCREB and CPEB1 in morphine tolerance, and that inhibition of MCU, pCREB, or CPEB1 may be useful in preventing the development of opioid tolerance.

IL-4 mediated by HSV vector suppresses morphine withdrawal response and decreases TNFα, NR2B, and pC/EBPß in the periaqueductal gray in rats.

Chronic opiates induce the development of physical dependence. Opioid physical dependence characterized by withdrawal symptoms, may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. Elucidation of the mechanisms involved in physical dependence is crucial to developing more effective treatment strategies for opioid dependence. Chronic morphine induces production of proinflammatory cytokines in regional-specific sites of the brain. Interleukin-4 (IL-4) is a prototypical anti-inflammatory cytokine that globally suppresses proinflammatory cytokines. Here, we used recombinant herpes simplex virus vector S4IL4 that encode mouse il4 gene to evaluate the therapeutic potential of IL-4 in naloxone-precipitation morphine withdrawal (MW). One week after microinjection of the vector S4IL4 into the PAG LacZ or mouse IL-4 immunoreactivity in the vlPAG was visualized. ELISA assay showed that vector S4IL4 into the PAG induced the expression of IL-4. S4IL4 blunted the morphine withdrawal syndrome. S4IL4 suppressed the upregulated TNFα, NR2B and pC/EBPß in the PAG induced by MW. These results show that inhibition of proinflammatory factor in the PAG suppressed MW. This study may provide a novel therapeutic approach to morphine physical withdrawal symptoms.

MnSOD mediated by HSV vectors in the periaqueductal gray suppresses morphine withdrawal in rats.

Morphine appears to be the most active metabolite of heroin; therefore, the effects of morphine are important in understanding the ramifications of heroin abuse. Opioid physical dependence (withdrawal response) may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. However, the exact mechanisms of morphine withdrawal (MW) are not clear yet, and its treatment remains elusive. Periaqueductal gray (PAG) is one of the important sites in the pathogenesis of MW. Here, we used recombinant herpes simplex virus (HSV) vectors that encode the sod2 gene expressing manganese superoxide dismutase (MnSOD) to evaluate its therapeutic potential in MW. Microinjection of HSV vectors expressing MnSOD into the PAG reduced the MW syndrome. MnSOD vectors suppressed the upregulated mitochondrial superoxide, and endoplasmic reticulum stress markers (glucose-related protein 78 (GRP78) and activating transcription factor 6 alpha (ATF6α)) in the PAG induced by MW. Immunostaining showed that mitochondrial superoxide, GRP78 and ATF6α were colocalized with neuronal nuclei (a neuronal-specific marker), suggesting that they are located in the neurons in the PAG. These results suggest that overexpression of MnSOD by HSV vectors may relieve opioid dependence. This study may provide a novel therapeutic approach to morphine physical withdrawal response.

Thrombomodulin Attenuates Inflammatory Damage Due to Liver Ischemia and Reperfusion Injury in Mice in Toll-Like Receptor 4-Dependent Manner.

Liver ischemia reperfusion injury (IRI) is an important problem in liver transplantation. Thrombomodulin (TM), an effective drug for disseminated intravascular coagulation, is also known to exhibit an anti-inflammatory effect through binding to the high-mobility group box 1 protein (HMGB-1) known as a proinflammatory mediator. We examined the effect of recombinant human TM (rTM) on a partial warm hepatic IRI model in wild-type (WT) and toll-like receptor 4 (TLR-4) KO mice focusing on the HMGB-1/TLR-4 axis. As in vitro experiments, peritoneal macrophages were stimulated with recombinant HMGB-1 protein. The rTM showed a protective effect on liver IRI. The rTM diminished the downstream signals of TLR-4 and also HMGB-1 expression in liver cells, as well as release of HMGB-1 from the liver. Interestingly, neither rTM treatment in vivo nor HMGB-1 treatment in vitro showed any effect on TLR-4 KO mice. Parallel in vitro studies have confirmed that rTM interfered with the interaction between HMGB-1 and TLR-4. Furthermore, the recombinant N-terminal lectin-like domain 1 (D1) subunit of TM (rTMD1) also ameliorated liver IRI to the same extent as whole rTM. Not only rTM but also rTMD1 might be a novel and useful medicine for liver transplantation. This is the first report clarifying that rTM ameliorates inflammation such as IRI in a TLR-4 pathway-dependent manner.

HSV vector-mediated GAD67 suppresses neuropathic pain induced by perineural HIV gp120 in rats through inhibition of ROS and Wnt5a.

Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating chronic condition that is severe and unrelenting. Despite the extensive research, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments. Loss of GABAergic tone may have an important role in the neuropathic pain state. Glutamic acid decarboxylase 67 (GAD67) is one of the isoforms that catalyze GABA synthesis. Here, we used recombinant herpes simplex virus (HSV-1) vectors that encode gad1 gene to evaluate the therapeutic potential of GAD67 in peripheral HIV gp120-induced neuropathic pain in rats. We found that (1) subcutaneous inoculation of the HSV vectors expressing GAD67 attenuated mechanical allodynia in the model of HIV gp120-induced neuropathic pain, (2) the anti-allodynic effect of GAD67 was reduced by GABA-A and-B receptors antagonists, (3) HSV vectors expressing GAD67 reversed the lowered GABA-IR expression and (4) the HSV vectors expressing GAD67 suppressed the upregulated mitochondrial superoxide and Wnt5a in the spinal dorsal horn. Taken together, our studies support the concept that recovering GABAergic tone by the HSV vectors may reverse HIV-associated neuropathic pain through suppressing mitochondrial superoxide and Wnt5a. Our studies provide validation of HSV-mediated GAD67 gene therapy in the treatment of HIV-related neuropathic pain.

Comparison of direct and indirect occlusal contact examinations with different clenching intensities.

The aims of this study were to examine the change of occlusal contact area following the increment of clenching intensity using silicone materials and electromyography (EMG) in normal subjects and to compare direct intra-oral examination with indirect examination using dental casts mounted by means of two impression methods. Participants were 7 men and 5 women with no more than one missing tooth per quadrant and no pain in the head and neck region. During the task, intercuspal position was maintained with minimal force, 20% maximum voluntary contraction (MVC) and 40% MVC using electromyography visual feedback. Three types of occlusal contact examinations were performed with the aid of blue silicone material in randomised order: (i) intra-oral direct occlusal contact examination (DE), (ii) indirect occlusal contact examination with dental casts using conventional impression method (IEC) and (iii) using occlusal impression method (IEO). Total occlusal contact area during DE and IEO significantly increased from baseline to 20% MVC and from baseline to 40% MVC, but not during IEC. Total occlusal contact area during DE in all tooth clenching conditions was significantly larger compared to IEO and IEC (P < 0·05). At 40% MVC, total occlusal contact area during IEO was significantly larger than during IEC (P < 0·05). These findings suggest that indirect occlusal contact examinations may not accurately reflect the intra-oral occlusal condition. If the intra-oral condition is reproduced using dental casts, these findings also suggest the occlusal impression method was more accurate compared to the conventional method (240 words).

Lymphaticovenular anastomosis to prevent cellulitis associated with lymphoedema.

BACKGROUND: One of the complications of lymphoedema is recurrent cellulitis. The aim was to determine whether lymphaticovenous anastomosis (LVA) was effective at reducing cellulitis in patients with lymphoedema. METHODS: This was a retrospective review of patients with arm/leg lymphoedema who underwent LVA. The frequency of cellulitis was compared before and after surgery. The diagnostic criteria for cellulitis were a fever of 38·5°C or higher, and warmth/redness in the affected limb(s). RESULTS: A total of 95 patients were included. The mean number of episodes of cellulitis in the year preceding surgery was 1·46, compared with 0·18 in the year after surgery (P < 0·001). CONCLUSION: LVA reduced the rate of cellulitis in these patients with lymphoedema.

Search for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ in Super-Kamiokande.

We present the results of searches for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ using data from a combined 172.8 kt·yr exposure of Super-Kamiokande-I,-II, and-III. We set lower limits on the partial lifetime for each of these modes: τn→ν[over ¯]π0>1.1×10(33) years and τp→ν[over ¯]π+>3.9×10(32) years at a 90% confidence level.

Search for dinucleon decay into kaons in Super-Kamiokande.

A search for the dinucleon decay pp → K+ K+ has been performed using 91.6 kton·yr data from Super-Kamiokande-I. This decay provides a sensitive probe of the R-parity-violating parameter λ112''. A boosted decision tree analysis found no signal candidates in the data. The expected background was 0.28±0.19 atmospheric neutrino induced events and the estimated signal detection efficiency was 12.6%±3.2%. A lower limit of 1.7×10(32) years has been placed on the partial lifetime of the decay O16 → C14K+ K+ at 90% C.L. A corresponding upper limit of 7.8×10(-9) has been placed on the parameter λ112''.

Hepatic arterial complications in adult living donor liver transplant recipients: a single-center experience of 673 cases.

BACKGROUND: Hepatic arterial reconstruction during living donor liver transplantation (LDLT) is a very delicate and technically complicated procedure. Post-LDLT hepatic arterial complications are associated with significant morbidity and mortality. METHODS: We retrospectively analyzed the details of post-operative hepatic arterial complications in 673 consecutive adult LDLT recipients between January 1996 and September 2009. RESULTS: Hepatic arterial complications occurred in 43 of 673 adult recipients (6.4%) within a median of 13 post-transplant days (range, 1-63). These included hepatic artery thrombosis (including anastomotic stenosis) in 33 cases, anastomotic bleeding in seven cases, and rupture of anastomotic aneurysm in three cases. To treat these complications, surgical re-anastomosis was performed in 26 cases, while the other 17 cases underwent conservative therapies, including four angioplasties by interventional radiology. Biliary complications after hepatic arterial complications occurred in 17 cases. The overall survival rate after LDLT was significantly lower in the hepatic arterial complication group compared with that in the non-complication group (60.7% vs. 80.1% at one yr, 44.3% vs. 74.2% at five yr, respectively; p < 0.001). Multivariate analysis showed that the extra-anatomical anastomosis (p = 0.011) was the only independent risk factor for hepatic arterial complications. CONCLUSION: Because hepatic arterial complications after LDLT are associated with poor patient survival, early diagnosis and immediate treatment are crucial. The anatomical anastomosis may be the first choice for the hepatic arterial reconstruction to the extent possible.

Therapeutic strategy for lower limb lymphedema and lymphatic fistula after resection of a malignant tumor in the hip joint region: a case report.

Lymphatic fistula complicating lymphedema is thought to occur due to communication between lymph vessels and the skin, which has yet to be shown objectively. The objective of this case report is to show the pathology and treatment using simultaneous lymphatic fistula resection and lymphatico-venous anastomosis (LVA). A 40-year-old woman underwent extended resection and total hip arthroplasty for primitive neuroectodermal tumor in the right proximal femur 23 years ago. Right lower limb lymphedema developed immediately after surgery and lymphatic fistula appeared in the posterior thigh. On ICG lymphography, lymph reflux toward the distal side dispersing in a fan-shape reticular pattern from the lymphatic fistula region was noted after intracutaneous injection of ICG into the foot. We performed simultaneous lymphatic fistula resection and of LVA. Pathological examination showed that the epidermis and stratum corneum of the healthy skin were lost in the lymphatic fistula region. Dilated lymph vessels were open in this region. The examinations provide the first objective evidence that the cause of lymphatic fistula may be lymph reflux from lymphatic stems to precollectors through lymphatic perforators.

Influence of different narrative instructions to record the occlusal contact with silicone registration materials.

This study examined the influence of narrative instructions on the occlusal contact area, occlusal contact point and masticatory muscle activities in normal subjects. Twelve healthy men and 12 healthy women with no more than one missing tooth per quadrant participated. Surface EMG was recorded from the masseter and temporal muscle. As a control measurement, intercuspal position was maintained to produce a habitual clenching record (NCR) while the occlusal contact area and occlusal contact point was recorded by means of silicone material. Subsequently, the occlusal contact area was recorded with the narrative instruction for minimum clenching record (MCR), light clenching record (LCR) and strong clenching record (HCR). While the EMG activity (%MVC) increased modestly from MCR to LCR (from 9·3 ± 2·0% to 11·5 ± 1·5%), the occlusal contact area increased rapidly (from 17·2 ± 11·3 mm(2) to 26·8 ± 15·6 mm(2) ) (P < 0·05). Both EMG activity and occlusal contact area increased gradually from LCR to NCR (to 17·7 ± 2·0% and to 31·4 ± 14·2 mm(2) , respectively). Finally, EMG activity still increased from NCR to HCR (to 44·5 ± 3·7%) (P < 0·05), but the occlusal contact area remained stable (to 36·8 ± 16·6 mm(2) ). Occlusal contact points at left posterior, right posterior, anterior and total area were not significantly different between each task. This study showed that narrative instructions while recording the bite can result in largely stable occlusal contact area. An adequate narrative instruction may therefore contribute to taking a stable occlusal recording in natural dentition.

Analysis of brain and muscle activity during low-level tooth clenching--a feasibility study with a novel biting device.

In electromyographic (EMG) and functional magnetic resonance imaging (fMRI) studies, muscle and brain activity was compared during low levels of tooth clenching using a novel biting device to control bite force. A total of 21 healthy subjects performed motor tasks, comprising tooth clenching at 5, 10 and 20 N. During all measurements, subjects kept the novel bite device between the anterior teeth during tooth clenching. The EMG study (n = 15) characterised jaw muscle activity for the three motor tasks and demonstrated significant differences in root mean square (RMS) EMG amplitude between 5-, 10- and 20-N tooth clenching (F = 46.21, P < 0.001). There were no differences in variability of muscle activity between the three tooth-clenching levels. In an fMRI pilot study (n = 6), statistical comparisons were used to identify brain regions with significant activation in the subtraction of baseline from 5- or 20-N tooth-clenching activity. 5- and 20-N tooth clenching significantly and bilaterally activated the sensorimotor cortex, supplementary motor area, cerebellum and basal ganglia (P < 0.05, corrected for multiple comparisons). However, activation of each brain region did not differ significantly between two tooth-clenching tasks. Based on these preliminary findings, we propose that the novel biting device may be useful in further fMRI studies on controlled jaw muscle activation patterns in different craniofacial pain conditions. In addition, our fMRI result suggests that there are no significant differences in brain activity within low levels of tooth clenching with controlled force.

Evidence for the appearance of atmospheric tau neutrinos in super-Kamiokande.

Super-Kamiokande atmospheric neutrino data were fit with an unbinned maximum likelihood method to search for the appearance of tau leptons resulting from the interactions of oscillation-generated tau neutrinos in the detector. Relative to the expectation of unity, the tau normalization is found to be 1.42 ± 0.35(stat)(-0.12)(+0.14)(syst) excluding the no-tau-appearance hypothesis, for which the normalization would be zero, at the 3.8σ level. We estimate that 180.1 ± 44.3(stat)(-15.2)(+17.8) (syst) tau leptons were produced in the 22.5 kton fiducial volume of the detector by tau neutrinos during the 2806 day running period. In future analyses, this large sample of selected tau events will allow the study of charged current tau neutrino interaction physics with oscillation produced tau neutrinos.

Thigh muscularity and strength in teenage soccer players.

This study examined the thigh muscularity and strength capability in early adolescent soccer players. The cross-sectional areas (CSAs) of the thigh muscles and dynamic strength during knee extension and flexion at 1.05 rad/s were determined twice at an interval of 6 months in 24 male soccer players aged 12-13 years and 11 age- and body height-matched non-athletes. After 6 months, muscle CSA and dynamic strength increased without significant interaction of time and group. Thigh total muscle CSA was not significantly affected by group, but the value relative to either thigh CSA or body mass was higher in soccer players. While knee flexion strength was similar between the 2 groups, knee extension strength was greater in soccer players than in non-athletes, even in terms of strength relative to CSA. The current results indicate that, compared with age- and body height-matched non-athletes, early adolescent soccer players are characterized by higher relative distribution of muscle mass within the thigh and higher knee extension strength relative to the quadriceps CSA. During the growth stage in which body height begins to increase markedly, however, participation in competitive soccer training does not increase the rate of development in thigh muscularity and strength.

Influence of the thickness of silicone registration material as a means for occlusal contact examination--an explorative study with different tooth clenching intensities.

This study explored the influence of the thickness of silicone registration material on evaluation of the occlusal contact area and number of occlusal contact points, during increasing tooth clenching conditions in normal subjects. Twenty-four subjects with no more than one missing tooth per quadrant participated. Surface electro-myography was recorded from the masseter muscle. As a baseline measurement, intercuspal position was maintained with minimal force, and occlusal contact was recorded using blue silicone material. Occlusal contact was also recorded at 20% maximum voluntary contraction (MVC) and 40% MVC using visual feedback. The occlusal contact area and number of occlusal contact points were analysed using five levels of thickness of silicone registration material: Level 1 (0-149 µm); Level 2 (0-89 µm); Level 3 (0-49 µm); Level 4 (0-29 µm); and Level 5 (0-4 µm). The anterior part and the left and right posterior regions of the dental arch were analysed separately. At all detection levels, the occlusal contact area significantly increased from baseline to 20% MVC and to 40% MVC in the molar area (P < 0·05). In the anterior part, the occlusal contact area significantly increased from baseline to 20% MVC and to 40% MVC only when using Level 5. The number of occlusal contact points significantly increased from baseline to 20% MVC and to 40% MVC only when using Level 5 in the molar area (P < 0·05). It suggested that occlusal contacts may be different at low tooth clenching intensity with potential effects on the teeth or periodontal tissues.

Pediatric liver transplantation using reduced and hyper-reduced left lateral segment grafts: a 10-year single-center experience.

Few studies have examined the long-term outcomes and prognostic factors associated with pediatric living living-donor liver transplantation (LDLT) using reduced and hyper-reduced left lateral segment grafts. We conducted a retrospective, single-center assessment of the outcomes of this procedure, as well as clinical factors that influenced graft and patient survival. Between September 2000 and December 2009, 49 patients (median age: 7 months, weight: 5.45 kg) underwent LDLT using reduced (partial left lateral segment; n = 5, monosegment; n = 26), or hyper-reduced (reduced monosegment grafts; n = 18) left lateral segment grafts. In all cases, the estimated graft-to-recipient body weight ratio of the left lateral segment was more than 4%, as assessed by preoperative computed tomography volumetry, and therefore further reduction was required. A hepatic artery thrombosis occurred in two patients (4.1%). Portal venous complications occurred in eight patients (16.3%). The overall patient survival rate at 1, 3 and 10 years after LDLT were 83.7%, 81.4% and 78.9%, respectively. Multivariate analysis revealed that recipient age of less than 2 months and warm ischemic time of more than 40 min affected patient survival. Pediatric LDLT using reduced and hyper-reduced left lateral segment grafts appears to be a feasible option with acceptable graft survival and vascular complication rates.

Effect of portal haemodynamics on liver graft and intestinal mucosa after small-for-size liver transplantation in swine.

BACKGROUND: After small-for-size graft (SFSG) transplantation, elevated portal venous pressure (PVP) may lead to postoperative liver damage. Herein we evaluated the impact of portocaval shunt (PCS) to control PVP on liver grafts and intestine following SFSG transplantation. METHODS: Nineteen SFSG transplantations were performed with 30% of native liver in swine. Swine were divided into 3 groups: a high-flow shunt group (HS: n = 7), in which portal venous flow (PVF) was reduced with a 10-mm diameter PCS; a low-flow shunt group (LS: n = 6), in which PVF was reduced with a 5-mm diameter PCS, and a no-shunt group (NS: n = 6), in which no PCS was placed. RESULTS: Seven-day survivals were 83.3% in NS, 100% in LS and 0% in HS (p = 0.0088). PVP was significantly higher in the NS group (p = 0.0001; mean ± SEM NS/LS/HS: 20.5 ± 0.7/14.0 ± 1.2/11.6 ± 0.5 mm Hg). The LS group exhibited the highest compliance (PVF/PVP; NS/LS/HS 42.7 ± 10.9/44.6 ± 4.9/37.7 ± 8.3 ml/min/mm Hg; p = 0.009), the lowest aspartate aminotransferase (NS/LS/HS 562 ± 18/370 ± 55/720 ± 130 IU/l; p = 0.0493), and suppressed deleterious alternations of the hepatic parenchyma and intestinal mucosa. CONCLUSIONS: Portal hypertension after SFSG transplantation impaired liver and intestinal mucosa; however, inadequate portal flow impaired not only the liver, but also survival.