Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model.

OBJECTIVE: We have reported that fibrotic changes in infrapatellar fat pad (IFP) after acute joint inflammation are closely associated with persistent pain in rats. In this study, to examine the effects of anti-fibrotic treatment on persistent pain, we used C-type natriuretic peptides (CNP) at the recovery phase after acute joint inflammation. DESIGN: Thirty-two male Wistar rats were used in this study. Monoiodoacetic acid (MIA) was injected intra-articularly to induce IFP fibrosis and persistent pain. CNP was injected after acute inflammatory phase in the same knee joint. Time-course pain-avoidance behavior tests and histological analyses were performed to examine the effects of CNP. RESULTS: Histological evaluations indicated that intra-articular injection of CNP inhibited fibrotic changes in IFP after acute inflammation. Incapacitance tests indicated that MIA injection into rat knee joint quickly decreased the percent weight on ipsilateral limb. In the vehicle group, the decrease was maintained up to day 28, suggesting that pain persistence occurred after acute inflammation (Day 0/Day 28, Est Dif -8.15, CI -10.78∼-5.53, Linear mixed-effect model). In contrast, the pain was alleviated in the CNP group after day 14 (Day0/Day 14, -0.51, -2.62-1.59). In addition, we observed significant improvement in the degree of articular cartilage degeneration at day 14 in the CNP group (OARSI score: vehicle 16.14 ± 4.37 vs CNP 6.87 ± 3.44, P < 0.01; Wilcoxon rank sum test). CONCLUSION: Fibrotic changes in IFP may play important roles in both persistent pain and articular cartilage degeneration.

Epidemiology of hospitalised paediatric community-acquired pneumonia and bacterial pneumonia following the introduction of 13-valent pneumococcal conjugate vaccine in the national immunisation programme in Japan.

Studies on community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP) related to the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in Asia are scarce. This study aimed to investigate the epidemiological and microbiological determinants of hospitalised CAP and PP after PCV13 was introduced in Japan. This observational hospital-based surveillance study included children aged ⩽15 years, admitted to hospitals in and around Chiba City, Japan. Participants had bacterial pneumonia based on a positive blood or sputum culture for bacterial pathogens. Serotype and antibiotic-susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae isolates from patients with bacterial pneumonia were assessed. The CAP hospitalisation rate per 1000 child-years was 17.7, 14.3 and 9.7 in children aged <5 years and 1.18, 2.64 and 0.69 in children aged 5-15 years in 2008, 2012 and 2018, respectively. There was a 45% and 41% reduction in CAP hospitalisation rates, between the pre-PCV7 and PCV13 periods, respectively. Significant reductions occurred in the proportion of CAP due to PP and PCV13 serotypes. Conversely, no change occurred in the proportion of CAP caused by H. influenzae. The incidence of hospitalised CAP in children aged ⩽15 years was significantly reduced after the introduction of PCV13 in Japan. Continuous surveillance is necessary to detect emerging PP serotypes.

Distribution of anaerobic carbon monoxide dehydrogenase genes in deep subseafloor sediments.

Carbon monoxide (CO) is the simplest oxocarbon generated by the decomposition of organic compounds, and it is expected to be in marine sediments in substantial amounts. However, the availability of CO in the deep subseafloor sedimentary biosphere is largely unknown even though anaerobic oxidation of CO is a thermodynamically favourable reaction that possibly occurs with sulphate reduction, methanogenesis, acetogenesis and hydrogenesis. In this study, we surveyed for the first time the distribution of the CO dehydrogenase gene (cooS), which encodes the catalytic beta subunit of anaerobic CO dehydrogenase (CODH), in subseafloor sediment-core samples from the eastern flank of the Juan de Fuca Ridge, Mars-Ursa Basin, Kumano Basin, and off the Shimokita Peninsula, Japan, during Integrated Ocean Drilling Program (IODP) Expeditions 301, 308 and 315 and the D/V Chikyu shakedown cruise CK06-06, respectively. Our results show the occurrence of diverse cooS genes from the seafloor down to about 390 m below the seafloor, suggesting that microbial communities have metabolic functions to utilize CO in anoxic microbial ecosystems beneath the ocean floor, and that the microbial community potentially responsible for anaerobic CO oxidation differs in accordance with possible energy-yielding metabolic reactions in the deep subseafloor sedimentary biosphere. SIGNIFICANCE AND IMPACT OF THE STUDY: Little is known about the microbial community associated with carbon monoxide (CO) in the deep subseafloor. This study is the first survey of a functional gene encoding anaerobic carbon monoxide dehydrogenase (CODH). The widespread occurrence of previously undiscovered CO dehydrogenase genes (cooS) suggests that diverse micro-organisms are capable of anaerobic oxidation of CO in the deep subseafloor sedimentary biosphere.

Effect of periodontal surgery on oral health-related quality of life in patients who have completed initial periodontal therapy.

BACKGROUND AND OBJECTIVE: Patient-centered assessments are particularly important in periodontal treatment in which their concerns may differ from the traditional clinical endpoints. However, information is limited regarding the influence of periodontal surgery on patients' quality of life (QoL). The aim of the present study was to investigate the impact of surgical periodontal therapy on the oral health-related QoL of patients who have received initial periodontal therapy. METHODS: A three-center prospective clinical study design was used, with the study participants comprising patients with moderate to severe periodontitis. Following initial periodontal therapy, the participants received either surgical or non-surgical periodontal treatment. The Oral Health-related Quality of Life Model for Dental Hygiene (OHRQL instrument), was used to assess participants' oral health-related QoL at each periodontal assessment interval: baseline (phase I), after initial therapy (phase II) and after surgery or during supportive periodontal therapy (phase III). RESULTS: Seventy-six patients (26 non-surgery, 50 surgery) completed the third phase of OHRQL assessment and were subjected to data analysis. From phase II to III, an improvement was achieved in all clinical parameters (p < 0.05-0.001) in the surgery group, whereas no such improvement was observed in the non-surgery group. In both groups, a significant difference in total OHRQL score was noted between phases I and III (p < 0.001 for surgery and p < 0.05 for non-surgery). The OHRQL domain scores for pain and eating/chewing function showed a significant improvement between these time points. However, no further significant improvement in OHRQL scores was achieved from phase II to III. CONCLUSION: A significant improvement in oral health-related QoL was noted between phases I and III in the surgery and non-surgery groups. Such improvement was less pronounced in the non-surgery vs. the surgery group. From phase II to III, neither surgery nor non-surgical treatment yielded significant improvement in oral health-related QoL.

An efficient approach to gem-difluorocyclopropylstannanes via highly regio- and stereoselective hydrostannylation of gem-difluorocyclopropenes and their unique ring-opening reaction to afford ß-fluoroallylic alcohols.

Treatment of various gem-difluorocyclopropenes with 1.2 equiv. of n-Bu3SnH in the presence of 20 mol% of Et3B at 80 °C for 4 h led to the quantitative formation of the hydrostannylated products in a highly regio- and trans-selective manner. Additionally, the prepared trans-gem-difluorocyclopropylstannanes were treated with 1.5 equiv. of MeLi in THF at -78 °C for 5 min, followed by quenching the reaction with various agents, such as H2O, alcohols, carboxylic acids, and tosylamide, to give the corresponding ß-fluoroallylic alcohols, ethers, esters, and amides respectively with exclusive Z selectivity in acceptable yields.

Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer.

BACKGROUND: Recent clinical trials have shown that immune-checkpoint blockade yields a clinical response in a subset of individuals with advanced nonsmall-cell lung cancer (NSCLC). We examined whether the expression of programmed death-ligand 1 (PD-L1) is related to clinicopathologic or prognostic factors in patients with surgically resected NSCLC. PATIENTS AND METHODS: The expression of PD-L1 was evaluated by immunohistochemical analysis in 164 specimens of surgically resected NSCLC. Cell surface expression of PD-L1 in NSCLC cell lines was quantified by flow cytometry. RESULTS: Expression of PD-L1 in tumor specimens was significantly higher for women than for men, for never smokers than for smokers, and for patients with adenocarcinoma than for those with squamous cell carcinoma. Multivariate analysis revealed that the presence of epidermal growth factor receptor gene (EGFR) mutations and adenocarcinoma histology were significantly associated with increased PD-L1 expression in a manner independent of other factors. Cell surface expression of PD-L1 was also significantly higher in NSCLC cell lines positive for activating EGFR mutations than in those with wild-type EGFR. The EGFR inhibitor erlotinib downregulated PD-L1 expression in the former cell lines but not in the latter, suggesting that PD-L1 expression is increased by EGFR signaling conferred by activating EGFR mutations. A high level of PD-L1 expression in resected tumor tissue was associated with a significantly shorter overall survival for NSCLC patients. CONCLUSIONS: High expression of PD-L1 was associated with the presence of EGFR mutations in surgically resected NSCLC and was an independent negative prognostic factor for this disease.

Potential application of munguba butter in the formulation of nanoemulsified systems.

Munguba butter has bioactive compounds such as vitamin E and phytosterols, which has valued its application in the development of new products, with advantages in its use in emulsified formulations. Therefore, the objective was to develop and evaluate the stability of a nanoemulsion containing munguba butter as the oily phase. Munguba butter was extracted by the ultrasound assisted method and its HLB (hydrophilic-lipophilic balance) was determined. Next, formulations varying the concentration of butter from 1-40% were developed and classified into liquid or solid emulsion and phase separation. Liquid emulsions were evaluated for hydrodynamic particle diameter, polydispersity index (PDI), Zeta potential (ζ), rheological characterization, and stability assays. The butter had an HLB of 6.98. The NE 1.0% formulation was selected and demonstrated to be unstable at high temperatures (45 ± 2 °C) and remained stable at room temperature, refrigeration and light radiation for 90 days. Munguba butter, because it has high amounts of saturated fatty acids, hinders its application in the development of new products. However, the success in the development of the NE 1.0% formulation is noteworthy, remaining stable when exposed to refrigeration, room temperature and light radiation.

Dental findings in a child with osteopathia striata with cranial sclerosis (OS-CS): a case report.

The dental management of an 8-year-old girl with osteopathia striata with cranial sclerosis (OS-CS) is described. The girl presented with various oral abnormalities. The aim of this case report was to describe in detail the dental findings in a patient with OC-CS and the precautions to be taken when planning treatment. In the present case, many dental anomalies, such as delayed eruption of the permanent teeth, obliteration of the dental pulp, short roots, fused roots and taurodontism, were detected. In patients with OS-CS, routine dental care from an early stage is recommended to manage this anomaly properly.

The potential antioxidant activity of incorporating bacaba (Oenocarpus bacaba Mart.) extract into a nanoemulsion system with baru oil.

The bacaba (Oenocarpus bacaba Mart.) peel corresponds to 15% of the whole fruit and is rich in antioxidants with potential application in product development. In nanotechnology, emulsified formulations such as nanoemulsions stand out for providing modified release and improving the bioavailability of conveyed substances. The aim of this work was to develop nanoemulsified systems from baru oil containing hydroalcoholic extract from the bacaba peel, evaluate their stability and antioxidant potential. After the HLB (Hydrophilic-lipophilic balance) determination of the baru oil, thirty-two formulations were developed, varying the proportions of surfactants, aqueous phase, and baru oil. Of those 32, 16 formed emulsified systems, and the ones with a higher amount of oil (20%) were incorporated with the BPE. The systems were submitted to stability studies to verify their viability. After that, several tests were performed, such as rheological characteristics, hydrodynamic diameter of the droplets, polydispersion index, zeta potential, and antioxidant potential by DPPH and ABTS+ radical scavenging methods. After the studies, two samples remained stable and presented a non-Newtonian pseudoplastic profile with thixotropy, hydrodynamic diameter of less than 200 nm, monodispersity, and negative zeta potential. The BPE showed antioxidant potential, with superior activity when incorporated into the nanoemulsified system. A strong negative correlation was found between the two antioxidant methods, where both demonstrated the same profile of potential antioxidant activity for the extract and formulations. The studied formulation showed that the use of BPE is a viable alternative for the development of new products based on sustainable technologies.

Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias.

Idiopathic interstitial pneumonias (IIPs) are histopathologically classified into several types, including usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and cryptogenic organising pneumonia (COP). We investigated whether periostin, a matrix protein, could be used as a biomarker to assess histopathological types of IIPs. We performed immunohistochemical analyses in each histopathological type of IIP, examined serum levels of periostin in IIP patients and analysed the relationship between serum levels of periostin and the pulmonary functions in patients with idiopathic pulmonary fibrosis (IPF). Periostin was strongly expressed in lungs of UIP and fibrotic NSIP patients, whereas expression of periostin was weak in the lungs of cellular NSIP and COP patients, as well as in normal lungs. Serum levels of periostin in IPF were significantly higher than those of healthy subjects and COP patients. Furthermore, periostin levels in IPF patients were inversely correlated with their pulmonary functions. Thus, we have found that periostin is a novel component of fibrosis in IIP. Periostin may be a potential biomarker to distinguish IIP with fibrosis.

Tolvaptan reduces the required amount of albumin infusion in patients with decompensated cirrhosis with uncontrolled ascites : a multicenter retrospective propensity score-matched cohort study.

Background: The aim of this retrospective study was to determine whether tolvaptan treatment reduces the amount of albumin administered, volume of ascites removed, and frequency of paracentesis procedures in patients with decompensated cirrhosis with uncontrolled ascites with conventional diuretics. Patients and methods: The control (C) group included patients treated with conventional diuretics. The tolvaptan (T) group included patients treated with both tolvaptan and conventional diuretics. Both groups were matched according to baseline parameters. The amount of albumin administered, volume of ascites removed, and frequency of paracentesis within 30 days of onset of uncontrolled ascites were compared between the two groups. Results: After matching, 74 patients (C=37, T=37) were included. Baseline parameters (C vs. T group) were as follows: age, 69.5 ± 9.3 vs. 70.4 ± 11.0 years (p = 0.702) ; males, 24 (64.9%) vs. 25 (67.6%) (p = 0.999) ; patients with hepatocellular carcinoma, 17 (45.9%) vs. 18 (48.6%) (p = 0.999) ; serum albumin levels at treatment initiation, 2.76 ± 0.48 vs. 2.73 ± 0.49 g/dL (p = 0.773), and serum creatinine levels at treatment initiation, 1.18 ± 1.23 vs. 1.09 ± 0.48 g/dL (p = 0.679). In the C vs. T groups, respectively, mean amount of albumin administered was 51.0 ± 31.4 vs. 33.4 ± 29.8 g/month (p = 0.016) ; mean volume of ascites removed was 2,905 ± 4,921 vs. 1,824 ± 3,185 mL/month (p = 0.266) ; and mean frequency of paracentesis was 0.92 ± 1.46 vs. 0.89 ± 1.45 procedures (p = 0.937). Conclusions: Tolvaptan reduced the use of albumin infusion in patients with decompensated cirrhosis and was effective and acceptable for uncontrolled ascites.

CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation.

Immune and inflammatory systems are controlled by multiple cytokines, including interleukins (ILs) and interferons. These cytokines exert their biological functions through Janus tyrosine kinases and signal transducer and activator of transcription (STAT) transcription factors. We recently identified two intrinsic Janus kinase (JAK) inhibitors, JAK binding protein (JAB; also referred to as suppressor of cytokine signaling [SOCS1]/STAT-induced STAT inhibitor [SSI1]) and cytokine-inducible SH2 protein (CIS)3 (or SOCS3/SSI3), which play an essential role in the negative regulation of cytokine signaling. We have investigated the role of STATs and these JAK inhibitors in intestinal inflammation. Among STAT family members, STAT3 was most strongly tyrosine phosphorylated in human ulcerative colitis and Crohn's disease patients as well as in dextran sulfate sodium (DSS)-induced colitis in mice. Development of colitis as well as STAT3 activation was significantly reduced in IL-6-deficient mice treated with DSS, suggesting that STAT3 plays an important role in the perpetuation of colitis. CIS3, but not JAB, was highly expressed in the colon of DSS-treated mice as well as several T cell-dependent colitis models. To define the physiological role of CIS3 induction in colitis, we developed a JAB mutant (F59D-JAB) that overcame the inhibitory effect of both JAB and CIS3 and created transgenic mice. DSS induced stronger STAT3 activation and more severe colitis in F59D-JAB transgenic mice than in their wild-type littermates. These data suggest that hyperactivation of STAT3 results in severe colitis and that CIS3 plays a negative regulatory role in intestinal inflammation by downregulating STAT3 activity.

Large perinephric abscess in a patient on maintenance hemodialysis diagnosed by positron emission tomography combined with computed tomography (PET-CT).

Perinephric abscesses in patients on maintenance hemodialysis (HD) have seldom been reported. The case of a maintenance HD patient with a left perinephric abscess is reported. Although the lesion could not be visualized using other imaging examinations, using FDG and positron emission tomography combined with computed tomography (PET-CT), the patient was diagnosed as having a left perinephric abscess and nephrolithiasis. At the patient's request, the perinephric abscess was treated conservatively with antibiotic therapy alone, and it eventually remitted. This is the first case report of a perinephric abscess diagnosed by FDG PET-CT in a patient on maintenance HD. FDG PET-CT appears to be useful for identifying perinephric abscesses in HD patients, resulting in early diagnosis and appropriate therapy for this severe infection.

Neurotransmitter release from synaptotagmin-deficient clonal variants of PC12 cells.

Synaptotagmin (p65) is an abundant synaptic vesicle protein of neurons and contains regions similar to the regulatory domain of protein kinase C. These domains are thought to be involved in calcium-dependent interaction with membrane phospholipids during exocytosis. To assess the functional role of synaptotagmin, synaptotagmin-deficient clonal variants of PC12 cells were isolated. All of the variant cells released catecholamine and adenosine triphosphate in response to elevated intracellular concentrations of calcium, which suggests that synaptotagmin is not essential for secretion of catecholamine and adenosine triphosphate from PC12 cells.

Hereditary hemorrhagic telangiectasia in a patient with microscopic polyangiitis.

A 55-year-old Japanese woman with microscopic polyangiitis suffered repeated disturbance of consciousness and gastrointestinal bleeding. These problems were initially attributed to microscopic polyangiitis, but hereditary hemorrhagic telangiectasia was finally identified by further workup. Both microscopic polyangiitis and hereditary hemorrhagic telangiectasia are blood vessel-related diseases inducing similar symptoms. To our knowledge, this is the first observation of microscopic polyangiitis and hereditary hemorrhagic telangiectasia in the same patient. From a literature review of the clinical and pathologic manifestations of these diseases, a positive association may exist between the two diseases.

Surface tension of room temperature ionic liquids measured by dynamic light scattering.

Using dynamic light scattering techniques, we obtained the surface tension sigma, surface excess entropy S(sigma), surface excess enthalpy H(sigma), and viscosity eta for the following seven room temperature ionic liquids in a wide temperature range from 30 to around 140 degrees C: 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, 1-hexyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, N-methyl-N-propylpiperidinium bis(trifluoromethanesulfonyl)imide, N,N,N-trimethyl-N-propylammonium bis(trifluoromethanesulfonyl)imide, 1-butyl-3-methylimidazolium hexafluorophosphate, 1-hexyl-3-methylimidazolium hexafluorophosphate, and 1-octyl-3-methyl imidazolium hexafluorophosphate. We have found that sigma increases systematically with decreasing the anion size and the alkyl side chain length. On the other hand, S(sigma) and eta increase with decreasing the anion size but decrease with decreasing the alkyl chain length. H(sigma) seems to decrease with increasing the anion size, but it has no clear dependence on the alkyl chain length. We discuss the bulk and surface properties, referring to the Coulomb interactions and van der Waals interactions.

Bulk shear-mode contribution to thermally generated capillary waves on a room-temperature ionic-liquid surface.

In the present work, we show that the autocorrelation function of the capillary-wave displacement is expressed by the sum of the ordinary oscillator and the bulk shear-mode terms. The former is expressed by a simple damped oscillator form or a sum of exponentially damping functions depending on the extent of damping. The latter is also written by superposition of exponentially damping modes, and an analytically exact formulation is obtained. We performed surface dynamic light-scattering experiment for the surface of an ionic liquid, 1-butyl- 3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, and compared the experimental autocorrelation function with the theoretical one. We observed for the first time the bulk shear-mode contribution, and confirmed that the experimental data is well explained by the theoretical autocorrelation function.

The evaluation of whitening efficacy of cosmetic products using a human skin pigmentation spot model.

BACKGROUND: To establish a pigmentation spot model on human skin and to assess whitening efficacy for whitening products by this established pigmentation spot model. METHODS: Twenty subjects between 20 and 45 years old with skin phototype III or IV were selected. Three consecutive daily UV exposures were performed on buttocks of the subjects as follows: Day 1=1 minimal erythema dose (MED), Day 2=0.5 MED and Day 3=0.5 MED. After the first UV exposure, a selected whitening product was applied to the subjects twice a day on UV exposure area. The application of the whitening product to subjects on the exposed areas was continued till Day 27. CM2500d chromameter, Maxmeter MX18 and visual evaluation were used to assess changes of skin color. RESULTS: A pigmentation spot model after UV exposure was established. The measurement of the pigment spot showed that L* value declined abruptly at Day 3 and then slowly reached to a lowest point at Day 6. L* value of the pigment spot almost remained at the same level until Day 20, thereafter increased slowly. The a* value showed an abrupt increase at Day 3 and slowly reached to a maximal level at Day 6. The a* value slowly declined toward its baseline level. Likewise, the erythema index also increased significantly at Day 3, and reached to a maximal level at Day 6 and then slowly declined. However, L*, a* and erythema indices did not return to their baseline levels during the 27-day period of this study. On the other hand, b* value started to increase from Day 3 and such increase was observed continuously to Day 27. Melanin index also showed a slow increase during the first 3 days. It started to increase rapidly from Day 3 and a to maximal level at Day 9 and maintain at a plateau till Day 27 (with an exception at Day 13). To assess the whitening product by this pigmentation spot model, DeltaL, Deltab*, and DeltaM values were analyzed. It showed that absolute DeltaL value and Deltab*value of whitening products were lower than those values of the vehicle of the whitening product at each checkpoint, while DeltaM value of the whitening product was lower only at Day 9 and Day 20, although no statistically significant differences was found. The visual results also strongly supported that the whitening product enhanced the decrease of pigmentation. CONCLUSION: This study showed that repeated UV exposure was able to induce a long extensive period of pigment formation. The resulted pigmentation spot was able to maintain at an elevated level till Day 20. Clinical subjective evaluations together with combined objective instrument measurements were still important to assess whitening and spot-removing ability of a material due to the instrument limitation for color differentiations. This kind of pigmentation spot model can be used to assess whitening efficacy for whitening or spot-removing products. In addition, the combinations of subjective and objective methods were able to serve as advisable references to assess the whitening efficacy of products.

[Primary lung cancer protruding into right main bronchus, successfully treated with endoscopic neodymium yttrium aluminum garnet (Nd-YAG) laser].

Endoscopic neodymium yttrium aluminum garnet (Nd-YAG) laser treatment for endobronchial obstruction originating from the tumor provides a favorable outcome. A 67-year-old male patient with a chief complaint of cough and sputum had a primary lung cancer (squamous cell carcinoma) in the upper lobe of the right lung. The tumor projected into the right main bronchus through the upper lobe bronchus, which completely occluded the lumen of right main bronchus. Middle and lower lobes showed an obstructive pneumonia caused by its obstruction. Firstly, endoscopic Nd-YAG laser treatment for patency of right main bronchus was preoperatively performed with an aim to early improvement of obstructive pneumonia Since the inflammatory findings showed markedly improvement, a right upper sleeve lobectomy could safely be performed. The resected specimen of the tumor in the right upper lobe proved to be a case of complete resection with pathological stage IIIA (T3N1M0). When preoperative lung cancer patient has an obstructive pneumonia causing by the protruding tumor into the central airway, a patency treatment of bronchial airway using endoscopic Nd-YAG laser may lead to decrease a perioperative risk.