Effects of preemptive analgesia with intravenous acetaminophen on postoperative pain relief in patients undergoing third molar surgery: a prospective, single-blind, randomized controlled trial

BACKGROUND: The efficacy of preemptive analgesia in managing postoperative pain remains controversial. The aim of this study was to compare the efficacy of intravenous (IV) acetaminophen administered before or immediately after the surgical extraction of an impacted mandibular third molar. MATERIAL AND METHODS: This prospective randomized clinical trial included 120 patients. The patients were assigned to one of three groups: the preoperative-treatment group (pre-group), which received 1000 mg of IV acetaminophen 20 min before surgery; the postoperative-treatment group (post-group), which received 1000 mg of IV acetaminophen after surgery; the no-treatment group (control-group), which did not receive any analgesic. Rescue analgesic (60 mg loxoprofen) was issued to each patient, with instructions on self-administration if needed. For the rescue medication usage, the time of first loxoprofen usage and the total amount of loxoprofen consumption were obtained for a 17-hour period after surgery. We measured pain using the visual analogue scale at 1 hour and at 2, 3, 4, 5, and 15 hours after surgery. RESULTS: There was no significant difference in pain level among the three groups at any time interval. However, the pre-group demonstrated significantly lower rescue analgesic consumption and longer time until initial administration. CONCLUSIONS: Administration of IV acetaminophen before third molar surgery provides more effective pain control than postoperative administration and no treatment

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Effects of preemptive analgesia with intravenous acetaminophen on postoperative pain relief in patients undergoing third molar surgery: a prospective, single-blind, randomized controlled trial.

BACKGROUND: The efficacy of preemptive analgesia in managing postoperative pain remains controversial. The aim of this study was to compare the efficacy of intravenous (IV) acetaminophen administered before or immediately after the surgical extraction of an impacted mandibular third molar. MATERIAL AND METHODS: This prospective randomized clinical trial included 120 patients. The patients were assigned to one of three groups: the preoperative-treatment group (pre-group), which received 1000 mg of IV acetaminophen 20 min before surgery; the postoperative-treatment group (post-group), which received 1000 mg of IV acetaminophen after surgery; the no-treatment group (control-group), which did not receive any analgesic. Rescue analgesic (60 mg loxoprofen) was issued to each patient, with instructions on self-administration if needed. For the rescue medication usage, the time of first loxoprofen usage and the total amount of loxoprofen consumption were obtained for a 17-hour period after surgery. We measured pain using the visual analogue scale at 1 hour and at 2, 3, 4, 5, and 15 hours after surgery. RESULTS: There was no significant difference in pain level among the three groups at any time interval. However, the pre-group demonstrated significantly lower rescue analgesic consumption and longer time until initial administration. CONCLUSIONS: Administration of IV acetaminophen before third molar surgery provides more effective pain control than postoperative administration and no treatment.

Radial Spin Texture in Elemental Tellurium with Chiral Crystal Structure.

The chiral crystal is characterized by a lack of mirror symmetry and inversion center, resulting in the inequivalent right- and left-handed structures. In the noncentrosymmetric crystal structure, the spin and momentum of electrons are expected to be locked in the reciprocal space with the help of the spin-orbit interaction. To reveal the spin textures of chiral crystals, we investigate the spin and electronic structure in a p-type semiconductor, elemental tellurium, with the simplest chiral structure by using spin- and angle-resolved photoemission spectroscopy. Our data demonstrate that the highest valence band crossing the Fermi level has a spin component parallel to the electron momentum around the Brillouin zone corners. Significantly, we have also confirmed that the spin polarization is reversed in the crystal with the opposite chirality. The results indicate that the spin textures of the right- and left-handed chiral crystals are hedgehoglike, leading to unconventional magnetoelectric effects and nonreciprocal phenomena.

A candidate-SNP retrospective cohort study for fracture risk in Japanese Thoroughbred racehorses.

Fractures are medical conditions that compromise the athletic potential of horses and/or the safety of jockeys. Therefore, the reduction of fracture risk is an important horse and human welfare issue. The present study used molecular genetic approaches to determine the effect of genetic risk for fracture at four candidate SNPs spanning the myostatin (MSTN) gene on horse chromosome 18. Among the 3706 Japanese Thoroughbred racehorses, 1089 (29.4%) had experienced fractures in their athletic life, indicating the common occurrence of this injury in Thoroughbreds. In the case/control association study, fractures of the carpus (carpal bones and distal radius) were statistically associated with g.65809482T/C (P = 1.17 x 10-8 ), g.65868604G/T (P = 2.66 x 10-9 ), and g.66493737C/T (P = 6.41 x 10-8 ). In the retrospective cohort study using 1710 racehorses born in 2000, the relative risk (RR) was highest for male horses at g.65868604G/T, based on the dominant allele risk model (RR = 2.251, 95% confidence interval 1.407-3.604, P = 0.00041), and for female horses at g.65868604G/T, based on the recessive allele risk model (RR = 2.313, 95% confidence interval 1.380-3.877, P = 0.00163). Considering the association of these SNPs with racing performance traits such as speed, these genotypes may affect the occurrence of carpus fractures in Japanese Thoroughbred racehorses as a consequence of the non-genetic influence of the genotype on the distance and/or intensity of racing and training. The genetic information presented here may contribute to the development of strategic training programs and racing plans for racehorses that improve their health and welfare.

Reduced marine phytoplankton sulphur emissions in the Southern Ocean during the past seven glacials.

Marine biogenic sulphur affects Earth's radiation budget and may be an indicator of primary productivity in the Southern Ocean, which is closely related to atmospheric CO2 variability through the biological pump. Previous ice-core studies in Antarctica show little climate dependence of marine biogenic sulphur emissions and hence primary productivity, contradictory to marine sediment records. Here we present new 720,000-year ice core records from Dome Fuji in East Antarctica and show that a large portion of non-sea-salt sulphate, which was traditionally used as a proxy for marine biogenic sulphate, likely originates from terrestrial dust during glacials. By correcting for this, we make a revised calculation of biogenic sulphate and find that its flux is reduced in glacial periods. Our results suggest reduced dimethylsulphide emissions in the Antarctic Zone of the Southern Ocean during glacials and provide new evidence for the coupling between climate and the Southern Ocean sulphur cycle.

A protonic biotransducer controlling mitochondrial ATP synthesis.

In nature, protons (H+) play an important role in biological activities such as in mitochondrial ATP synthesis, which is driven by a H+ gradient across the inner membrane, or in the activation of acid sensing ion channels in neuron cells. Bioprotonic devices directly interface with the H+ concentration (pH) to facilitate engineered interactions with these biochemical processes. Here we develop a H+ biotransducer that changes the pH in a mitochondrial matrix by controlling the flow of H+ between a conductive polymer of sulfonated polyaniline and solution. We have successfully modulated the rate of ATP synthesis in mitochondria by altering the solution pH. Our H+ biotransducer provides a new way to monitor and modulate pH dependent biological functions at the interface between the electronic devices and biological materials.

Down-regulation of the two-component system and cell-wall biosynthesis-related genes was associated with the reversion to daptomycin susceptibility in daptomycin non-susceptible methicillin-resistant Staphylococcus aureus.

Daptomycin (DAP) is widely used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. The emergence of DAP non-susceptible MRSA strains during therapy is a major concern in clinical settings. Recent studies revealed that MRSA spontaneously reverts to a subsequent methicillin-susceptible S. aureus (MSSA) strain. However, it is not clear whether DAP non-susceptible MRSA has the ability to revert to a susceptible strain. We obtained an MRSA strain pair, DAP non-susceptible strain and subsequent DAP susceptible strain, from a patient. To understand the underlying mechanism by which DAP non-susceptible MRSA reverts to a susceptible strain, we performed genetic and phenotypic analysis in the strain pair. Although whole-genome analysis revealed four missense mutations, including L826F in mprF, in both strains, the net cell-surface charge was similar between the DAP non-susceptible and susceptible strains. However, the thickness of the cell wall was higher in the DAP non-susceptible strain, which was decreased to the same level as the control after reversion to the DAP susceptible strain. Moreover, the non-susceptible strain showed higher mRNA expression of the two-component system (TCS), such as VraSR, yycG and GraS, with the up-regulated transcription levels of cell-wall biosynthesis-related genes. The expression levels of those genes were decreased after reversion to the susceptible strain. These results indicated that DAP non-susceptibility due to up-regulation of the TCS and cell-wall biosynthesis-related genes may be reversible by the discontinuation of DAP, leading to reversion to the DAP susceptible phenotype.

Squamous cell carcinoma arising from lupus vulgaris with a >60-year history.

We report the case of a 71-year-old Japanese man with squamous cell carcinoma arising from lupus vulgaris on the face, >60 years after the appearance of the lupus vulgaris. The red plaque on the patient's face had been diagnosed as a hemangioma or rosacea at several hospitals, although he had had lung tuberculosis at the age of 4 and his father died from lung tuberculosis at 38 years of age. Although lupus vulgaris was the most frequent clinical form of true skin tuberculosis until the 1960s, it has become rare since then. Malignant tumors are known to occur in individuals with lupus vulgaris, with a reported rate of 0.5-10.5%. In light of Japan's "graying society," tuberculosis is still an important disorder, and clinicians must remain aware of cutaneous tuberculosis.

Diabetic peripheral neuropathy and prevalence of erectile dysfunction in Japanese patients aged <65 years with type 2 diabetes mellitus: The Dogo Study.

Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. The prevalence values of diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.

Depressive symptoms and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: the Dogo Study.

In several studies of patients with type 2 diabetes mellitus, a positive association between depressive symptoms and erectile dysfunction (ED) has been reported. No evidence exists, however, regarding the association between depressive symptoms and ED among Japanese patients with type 2 diabetes mellitus. Thus, we examined this issue among Japanese patients with type 2 diabetes mellitus. Study subjects were 469 male Japanese patients with type 2 diabetes mellitus, aged 19 years or over. ED, moderate to severe ED and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. Depressive symptoms were defined as present when a subject had a Self-Rating Depression Scale (SDS) score >49. Adjustment was made for age, body mass index, waist, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, coronary artery disease, stroke, glycated hemoglobin and diabetic neuropathy. The prevalence values of depressive symptoms, moderate to severe ED and severe ED were 15.1%, 64.2% and 51.0%, respectively. Depressive symptoms were independently positively associated with moderate to severe ED and severe ED (adjusted odds ratios were 2.23 (95% confidence interval (CI): 1.17-4.43) and 1.86 (95% CI: 1.04-3.41), respectively). In Japanese patients with type 2 diabetes mellitus, depressive symptoms may be associated with ED.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Fish collagen is an important panallergen in the Japanese population.

Collagen was identified as a fish allergen in early 2000s. Although its allergenic potential has been suggested to be low, risks associated with collagen as a fish allergen have not been evaluated to a greater extent. In this study, we aimed to clarify the importance of collagen as a fish allergen. Our results showed that 50% of Japanese patients with fish allergy had immunoglobulin E (IgE) against mackerel collagen, whereas 44% had IgE against mackerel parvalbumin. IgE inhibition assay revealed high cross-reactivity of mackerel collagen to 22 fish species (inhibition rates: 87-98%). Furthermore, a recently developed allergy test demonstrated that collagen triggered IgE cross-linking on mast cells. These data indicate that fish collagen is an important and very common panallergen in fish consumed in Japan. The high rate of individuals' collagen allergy may be attributable to the traditional Japanese custom of raw fish consumption.

Survival rates and prognostic factors of Epstein-Barr virus-associated hydroa vacciniforme and hypersensitivity to mosquito bites.

BACKGROUND: Epstein-Barr virus (EBV)-associated T/natural-killer lymphoproliferative disorders form a group of diseases that includes classical and systemic hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). Patients with systemic HV (sHV) and HMB often have a poor prognosis, although little is known about the prognostic factors. OBJECTIVES: To elucidate the prognostic factors of HV and HMB. METHODS: We studied clinicopathological manifestations, routine laboratory findings, anti-EBV titres, EBV DNA load and EBV-encoded gene expression, including expression of BZLF1, in 50 patients with classical HV (cHV), sHV, HMB only and HMB with HV (HMB + HV), and further analysed 30 patients who were available for follow-up. RESULTS: The median age of disease onset was 5 years (range 1-74). A follow-up study indicated that fatal outcomes were observed in three of eight patients with sHV, two of six patients with HMB only, and two of five patients with HMB + HV. The main causes of death were complications from haematopoietic stem-cell transplantation and multiorgan failure. There were no fatalities among the 11 patients with cHV. Univariate analysis revealed two poor prognostic indicators: (i) onset age > 9 years and (ii) the expression of an EBV-encoded immediate-early gene transcript, BZLF1 mRNA, in the skin lesions (P < 0·001 and P = 0·003, respectively). CONCLUSIONS: No prognostic correlation was observed in EBV-infected lymphocyte subsets, anti-EBV antibody titres or EBV DNA load. Late onset and EBV reactivation are both related to more severe phenotypes of the disease, and thus may predict a poor prognosis.

Hyperthermic intraperitoneal chemotherapy using a combination of mitomycin C,5-fluorouracil, and oxaliplatin in patients at high risk of colorectal peritoneal metastasis: A Phase I clinical study.

INTRODUCTION: The drugs and protocols used for hyperthermic intraperitoneal chemotherapy (HIPEC) vary among institutions. Here we show the efficacy of the 3-drug combination of mitomycin C (MMC), 5-fluorouracil (5FU), and oxaliplatin (OHP) in an in vitro simulation of HIPEC and the safety of HIPEC with these drugs during a Phase I study of patients at high risk of developing colorectal peritoneal metastasis. METHODS: To simulate HIPEC, we used HCT116 and WiDr cells to assess the growth inhibitory efficacy of MMC 2 µg/mL, 5FU 200 µg/mL, and OHP 40 µg/mL as single drugs or their combination after an exposure time of 30 min at 37 or 42 °C. In addition, nine patients underwent surgical resection of tumors and HIPEC with MMC, 5FU, and an escalating dose of OHP (90/110/130 mg/m²). Dose-limiting toxicity was monitored. RESULTS: In the simulation, the 3-drug combination showed marked tumor-suppressive effects compared with those from ten times higher dose of OHP 400 µg/mL, with significant augmentation under hyperthermic conditions. No dose-limiting toxicity occurred in the clinical study. Dose escalation was completed at the final level of OHP. CONCLUSIONS: The MMC-5FU-OHP combination showed marked growth inhibition against colorectal cancer cells under hyperthermic conditions in vitro. In the phase I study, the recommended dose of OHP was determined as 130 mg/m² when used with MMC and 5FU; HIPEC using MMC-5FU-OHP appears to be safe and feasible for patients at high risk of colorectal peritoneal metastasis.

Empirical growth curve estimation considering multiple seasonal compensatory growths of body weights in Japanese Thoroughbred colts and fillies.

Thoroughbred horses are seasonal mating animals, and their foals are born yearly in spring seasons. In northern regions or countries, the foals generally show a typical seasonal compensatory growth pattern, where their growth rate declines in winter and increases in the next spring. In this study, a new empirical approach is proposed to adjust for this compensatory growth when growth curve equations are estimated, by using BW of Japanese Thoroughbred colts and fillies raised in Hidaka, Hokkaido. Based on the traditional Richards growth curve equation, new growth curve equations were developed and fit to the weight-age data. The foals generally experience 2 major winter seasons before their debut in horseracing. The new equations had sigmoid subfunctions that can empirically adjust the first and second year compensatory growths, combined with the Richards biological parameter responsible for the maturity of animals. The unknown parameters included in the equations were estimated by SAS NLMIXED procedure. The goodness-of-fit was examined by using several indices of goodness-of-fit (i.e., Akaike's information criterion, Bayesian information criterion, -2 log likelihood, and residual sum of squares) for the multiple applications of the subfunctions. The indices indicated the best fit of the new equations including both subfunctions for the first and second compensatory growths to the weight-age data. The shapes of the growth curves were improved during the periods of compensatory growth. The proposed method is one of the useful approaches for adjusting multiple seasonal compensatory growths in growth curve estimations of Thoroughbreds and for the management of young horses during the compensatory periods.

Signal-dependent fra-2 regulation in skeletal muscle reserve and satellite cells.

Activator protein-1 (AP-1) is a ubiquitous transcription factor that paradoxically also has some tissue-specific functions. In skeletal muscle cells, we document that the AP-1 subunit, Fra-2, is expressed in the resident stem cells (Pax7-positive satellite cells) and also in the analogous undifferentiated 'reserve' cell population in myogenic cultures, but not in differentiated myofiber nuclei. Silencing of Fra-2 expression enhances the expression of differentiation markers such as muscle creatine kinase and myosin heavy chain, indicating a possible role of Fra-2 in undifferentiated myogenic progenitor cells. We observed that Fra-2 is a target of cytokine-mediated extracellular signal-regulated kinase-1/2 signaling in cultured muscle cells, and extensive mass spectrometry and mutational analysis identified S320 and T322 as regulators of Fra-2 protein stability. Interestingly, Fra-2 S320 phosphorylation occurs transiently in activated satellite cells and is extinguished in myogenin-positive differentiating cells. Thus, cytokine-mediated Fra-2 expression and stabilization is linked to regulation of myogenic progenitor cells having implications for the molecular regulation of adult muscle stem cells and skeletal muscle regeneration.