Step-down vs. step-up noxious stimulation: differential effects on pain perception and patterns of brain activation.

BACKGROUND: We hypothesize that pain and brain responses are affected by changes in the presentation sequence of noxious stimuli that are, overall, identical in intensity and duration. METHODS: During functional magnetic resonance imaging (fMRI) scanning, 21 participants experienced three patterns of noxious stimulation: Up-type (step-up noxious stimulation, 15 s), Down-type (step-down noxious stimulation, 15 s), and Down-up-type (decreasing and increasing pattern of noxious stimulation, 15 s). The total intensity and duration of the three noxious stimulation patterns were identical, but the stimulation sequences were different. RESULTS: Pain and unpleasantness ratings in the Down- and Down-up-type noxious stimulations were lower than in the Up-type noxious stimulation. The left prefrontal cortex [(PFC, BA (Brodmann area) 10, (-45, 50, 1)] was more highly activated in the Down- and Down-up-type noxious stimulations than in the Up-type noxious stimulation. The S1, S2, insula, bilateral PFC (BA 46), and midcingulate cortex were more highly activated in the Up-type noxious stimulation than in the Down-type noxious stimulation. PFC BA 10 was located at an inferior level compared to the bilateral PFC BA 46 (Z axis = 1 for BA 10, compared to 22 and 25 for the right and left BA 46, respectively). When cortisol level was increased, the left hippocampal cortex, along with the left parahippocampal cortex, was greatly activated for the Up-type noxious stimulation. CONCLUSION: When pain cannot be avoided in clinical practice, noxious stimuli should be applied to patients in a step-down pattern that delivers the most intense pain first and the least intense pain last.

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study.

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.

Subjective apnoea symptoms are associated with daytime sleepiness in patients with moderate and severe obstructive sleep apnoea: a retrospective study.

OBJECTIVES: Most previous studies have failed to show a relation between daytime sleepiness and apnoea severity in patients with obstructive sleep apnoea (OSA). We determined the relation between daytime sleepiness and subjective and objective apnoea severity in newly diagnosed patients with moderate-to-severe OSA. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 559 adults with newly diagnosed moderate and severe OSA. MAIN OUTCOME MEASURES: Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Subjective and objective apnoea severities were assessed using the Sleep Breathing Scale (SBS) and polysomnography respectively. Sleep quality and depressive symptoms were evaluated using Medical Outcomes Study-Sleep Scale and Beck Depression Inventory (BDI) respectively. RESULTS: The mean ESS score was 9.8 (SD 5.0). ESS score was correlated with SBS score (P < 0.001), apnoea-hypopnoea index (AHI) (P = 0.027), minimal oxygen saturation (MinSaO2 ) (P = 0.021), body mass index (BMI) (P = 0.007) and BDI score (P < 0.001). Linear regression analysis showed that higher SBS (P = 0.005) and BDI scores (P < 0.001) were associated with higher ESS score after controlling for gender, BMI and AHI. Apnoea-hypopnoea index, MinSaO2 and BMI were not independently related to ESS score. CONCLUSIONS: Daytime sleepiness was related to subjective OSA symptoms but not objective apnoea severity measured by polysomnography in patients with moderate-to-severe OSA. These findings suggest the usefulness of the subjective apnoea severity as an indicator of OSA disease severity.

A charge density study of π-delocalization and intermolecular interactions.

The compound trans-4,4'-azo-1,2,4-triazole (atrz) is a planar molecule with two planar triazole rings bridged by an azo group. The molecule is a good donor ligand and has an interesting π-delocalized character. In addition, intermolecular interactions in the crystalline state through π-π stacking are found between triazole rings with a very short inter-planar distance of 3.17 Å. The electron density distribution is obtained from both high resolution X-ray diffraction data at 100 K and density functional theory (DFT) calculations using the ωB97X-D functional. Bond characterization is performed in terms of the charge density distribution and the associated topological properties. The Laplacian distribution around each atom reveals the shape of the valence-shell charge concentration and demonstrates a sp(2) hybrid orbital shape for each atom in the molecule. The π-delocalization of the planar molecule is further illustrated by the Fermi-hole distribution. The weak intermolecular π-π interactions and hydrogen bonds are further illustrated by the Hirshfeld surface. The energies of weak intermolecular π-π interactions and hydrogen bonds have been calculated using ωB97X-D/6-311++G(3df,2p) at experimental geometry.

Barriers to providing oral health care to pre-school children-differences between paediatric dentists' and general dental practitioners' beliefs.

BACKGROUND: The unmet dental needs of pre-school children indicate there are barriers in 'accessing' appropriate oral health care and this warrants consideration of care providers' beliefs. OBJECTIVE: To explore the beliefs and attitudes of dentists in Hong Kong towards providing oral health care to pre-school children; and to determine difference in attitudes between general dental practitioners (GDPs) and paediatric dentists (PDs). METHODS: A random sample of 476 GDPs (-25% of all registered dentists) and all registered PDs (28) were invited to participate in the study. Both groups were asked to complete the Barriers to Childhood Caries Treatment (BaCCT) questionnaire: a 29-item measure considering child, parent, dentist and health care system factors. Differences in attitudes of GDPs and PDs were examined in bivariate and regression analyses. RESULTS: The overall response rate of the study was 61.5% (310/504). There were significant differences in overall BaCCT scores and across all domains between GDPs and PDs (p < 0.05). Furthermore, variations across many aspects (as described at an item level) were apparent. Regression analyses confirmed differences in BaCCT between GDPs and PDs, controlling for practice and other factors. CONCLUSIONS: Differences exist between GDPs' and PDs' perceptions of barriers to care for early childhood caries. This has implications for how to address 'access' issues with likely implications on how to overcome barriers to care for pre-school children.

Genetic testing in inherited polyposis syndromes - how and why?

There have been recent advances in genetic testing enabling accurate diagnosis of polyposis syndromes by identifying causative gene mutations, which is essential in the management of individuals with polyposis syndrome and predictive genetic testing of their extended families. There are some similarities in clinical presentation of various polyposis syndromes, which may pose a challenge to diagnosis. In this review, we discuss the clinical presentation of the main polyposis syndromes and the process of genetic testing, including the latest advancement and future of genetic testing. We aim to reiterate the importance of genetic testing in the management of polyposis syndromes, potential pitfalls associated with genetic testing and recommendations for healthcare professionals involved with the care of polyposis patients.

Alopecia in three macaque species housed in a laboratory environment.

Alopecia is a persistent problem in captive macaque populations and despite recent interest, no factors have been identified that can unequivocally explain the presence of alopecia in a majority of cases. Seasonal, demographic, and environmental factors have been identified as affecting alopecia presentation in rhesus macaques, the most widely studied macaque species. However, few studies have investigated alopecia rates in other macaque species. We report alopecia scores over a period of 12 months for three macaque species (Macaca nemestrina, M. mulatta, and M. fascicularis) housed at three indoor facilities within the Washington National Primate Research Center (WaNPRC) in Seattle. Clear species differences emerged with cynomolgus (M. fascicularis) showing the lowest alopecia rates and pigtails (M. nemestrina) the highest rates. Further analysis of pigtail and rhesus (M. mulatta) macaques revealed that sex effects were apparent for rhesus but not pigtails. Age and seasonal effects were evident for both species. In contrast to previous reports, we found that older animals (over 10 years of age) had improved alopecia scores in comparison to younger adults. This is the first report on alopecia rates in pigtail macaques and the first comparison of alopecia scores in pigtail, cynomolgus, and rhesus macaques housed under similar conditions.

Lost therapeutic potential of monocyte-derived dendritic cells through lost tissue homing: stable restoration of gut specificity with retinoic acid.

Human monocyte-derived dendritic cells (DC) (MoDC) are utilized for immunotherapy. However, in-vitro immunological effects are often not mirrored in vivo. We studied the tissue-homing potential of MoDC. Circulating monocytes and DC expressed different tissue-homing markers and, during in-vitro development of MoDC, homing marker expression was lost resulting in a 'homeless' phenotype. Retinoic acid (RA) induced gut-homing markers (ß7 and CCR9) and a regulatory phenotype and function [decreased human leucocyte antigen D-related (HLA-DR) and increased ILT3 and fluorescein isothiocyanate (FITC-dextran uptake) in MoDC]. RA-MoDC were less stimulatory and primed conditioned T cells with a gut-homing profile (ß7(+)CLA(-)). Unlike the normal intestinal microenvironment, that from inflamed colon of ulcerative colitis (UC) patients did not induce regulatory properties in MoDC. However, RA-MoDC maintained their regulatory gut-specific properties even in the presence of UC microenvironment. Therefore, MoDC may be ineffectual for immunotherapy because they lack tissue-homing and tissue-imprinting specificity. However, MoDC rehabilitation with gut-homing potential by RA could be useful in promoting immunotherapy in pathologies such as UC.

Association study of anti-Mullerian hormone and anti-Mullerian hormone type II receptor polymorphisms with idiopathic primary ovarian insufficiency.

STUDY QUESTION: Are the genetic polymorphisms of the anti-Müllerian hormone (AMH) and anti-Müllerian hormone type II receptor (AMHR2) genes associated with idiopathic primary ovarian insufficiency (POI) in a Korean population? SUMMARY ANSWER: The distribution of the AMH and the AMHR2 polymorphisms in a Korean POI population was not significantly different from controls. WHAT IS KNOWN ALREADY: AMH plays an important role in regulating both the primordial follicle recruitment and the cyclic selection of the antral follicles. The AMHR2 -482A>G polymorphism was associated with an earlier menopause and nulliparous women with the GG genotype had a 2.6 years earlier onset of menopause compared with the AA genotype women. Therefore, genetic variants in the AMH signal transduction pathway might affect the ovarian function of women. STUDY DESIGN, SIZE, DURATION: Case-control study. The subjects consisted of 211 idiopathic POI patients and 233 post-menopausal controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The frequency of the AMH Ile(49)Ser and AMHR2 -482A>G polymorphisms was analyzed in 211 patients with idiopathic POI and in 233 post-menopausal controls, and we also analyzed clinical characteristics, such as age at the time of POI and LH, FSH as well as estradiol levels according to the specific genotype. Genotyping for the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms was performed by a minor groove binder primer/probe Taqman assay. MAIN RESULTS AND THE ROLE OF CHANCE: The genotype distributions and allele frequencies for the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms were similar between the POI patients and the controls. Within POI population, the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms were not associated with age at the time of POI and LH, FSH as well as estradiol levels. Haplotype analysis also showed no significant difference between groups. LIMITATIONS, REASONS FOR CAUTION: Study is limited to a Korean population. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that genetic variants in the AMH signal transduction pathway may not influence the susceptibility of idiopathic POI. This is the first report on the association between the AMH and AMHR2 polymorphisms and idiopathic POI. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. This study was supported by a grant of Seoul National University Hospital Research Fund (04-2011-0870). TRIAL REGISTRATION NUMBER: N/A.

Endoscopic submucosal dissection for sessile, nonampullary duodenal adenomas.

Although endoscopic submucosal dissection (ESD) is increasingly utilized to treat early neoplasms of the gastrointestinal tract, its use for duodenal neoplasms is limited by the thin wall and narrow lumen of the duodenum. We have reviewed cases where ESD was used to treat sessile, nonampullary duodenal neoplasms. To do this, we retrospectively reviewed the medical records of patients treated with ESD for adenomas of the duodenum from January 2001 to December 2010, assessing the curative outcomes and complication rates. A total of 14 cases were reviewed. Mean patient age was 56.4 years. The mean size of tumors and mean size of the specimens were 17.1 mm and 26.4 mm, respectively. The en bloc resection rate with ESD was 78.6%, and the complete (R0) resection rate was 85.7%. No patient in the study experienced major bleeding. However, second-look endoscopy revealed minor bleeding requiring endoscopic homeostasis in one case (7.1%). Perforations were observed in five cases (35.7%). Two of the five patients with perforation underwent surgery. The ESD methods yielded acceptable curative resection rates for duodenal adenomas, although ESD was associated with a higher rate of perforation. Therefore, duodenal ESD should be performed with care and only in selected patients to avoid serious complications.

Comparative efficacy evaluation of disinfectants against severe acute respiratory syndrome coronavirus-2.

BACKGROUND: Disinfection is one of the most effective ways to block the rapid transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the prolonged coronavirus disease 2019 (COVID-19) pandemic, disinfectants have become crucial to prevent person-to-person transmission and decontaminate hands, clothes, facilities and equipment. However, there is a lack of accurate information on the virucidal activity of commercial disinfectants. AIM: To evaluate the virucidal efficacy of 72 commercially available disinfectants constituting 16 types of ingredients against SARS-CoV-2. METHODS: SARS-CoV-2 was tested with various concentrations of disinfectants at indicated exposure time points as recommended by the manufacturers. The 50% tissue culture infectious dose assay was used to calculate virus titre, and trypan blue staining and CCK-8 were used to assess cell viability after 3-5 days of SARS-CoV-2 infection. FINDINGS: This study found that disinfectants based on 83% ethanol, 60% propanol/ethanol, 0.00108-0.0011% sodium dichloroisocyanurate and 0.497% potassium peroxymonosulfate inactivated SARS-CoV-2 effectively and safely. Although disinfectants based on 0.05-0.4% benzalkonium chloride (BAC), 0.02-0.07% quaternary ammonium compound (QAC; 1:1), 0.4% BAC/didecyldimethylammonium chloride (DDAC), 0.28% benzethonium chloride concentrate/2-propanol, 0.0205-0.14% DDAC/polyhexamethylene biguanide hydrochloride (PHMB) and 0.5% hydrogen peroxide inactivated SARS-CoV-2 effectively, they exhibited cytotoxicity. Conversely, disinfectants based on 0.04-4% QAC (2:3), 0.00625% BAC/DDAC/PHMB, and 0.0205-0.14% and 0.0173% peracetic acid showed approximately 50% virucidal efficacy with no cytotoxicity. Citric acid (0.4%) did not inactivate SARS-CoV-2. CONCLUSION: These results indicate that most commercially available disinfectants exert a disinfectant effect against SARS-CoV-2. However, re-evaluation of the effective concentration and exposure time of certain disinfectants is needed, especially citric acid and peracetic acid.

Momentum-independent magnetic excitation continuum in the honeycomb iridate H3LiIr2O6.

Understanding the interplay between the inherent disorder and the correlated fluctuating-spin ground state is a key element in the search for quantum spin liquids. H3LiIr2O6 is considered to be a spin liquid that is proximate to the Kitaev-limit quantum spin liquid. Its ground state shows no magnetic order or spin freezing as expected for the spin liquid state. However, hydrogen zero-point motion and stacking faults are known to be present. The resulting bond disorder has been invoked to explain the existence of unexpected low-energy spin excitations, although data interpretation remains challenging. Here, we use resonant X-ray spectroscopies to map the collective excitations in H3LiIr2O6 and characterize its magnetic state. In the low-temperature correlated state, we reveal a broad bandwidth of magnetic excitations. The central energy and the high-energy tail of the continuum are consistent with expectations for dominant ferromagnetic Kitaev interactions between dynamically fluctuating spins. Furthermore, the absence of a momentum dependence to these excitations are consistent with disorder-induced broken translational invariance. Our low-energy data and the energy and width of the crystal field excitations support an interpretation of H3LiIr2O6 as a disordered topological spin liquid in close proximity to bond-disordered versions of the Kitaev quantum spin liquid.

Natural course of noncurative endoscopic resection of differentiated early gastric cancer.

BACKGROUND AND STUDY AIMS: Following noncurative endoscopic resection of early gastric cancer (EGC), the patient should be observed when the underlying disease is severe, the patient is elderly, or the patient refuses further treatment. The aim of this study was to analyze the clinical outcomes of patients with differentiated EGC who underwent noncurative endoscopic resection without additional treatment. PATIENTS AND METHODS: Included patients underwent noncurative endoscopic resection for differentiated EGC without additional treatment at the Asan Medical Center between July 1994 and January 2009. Clinical and oncological outcomes were analyzed. RESULTS: A total of 159 patients were included in the analysis. The median follow-up period was 33 months (interquartile range [IQR] 22 - 52 months). In total, 40 patients died (25.2 %) - 3 due to stomach cancer, 34 due to other causes, and 3 from unknown causes; the median survival time after endoscopic treatment for these patients was 27.5 months (IQR 13.8 - 48.3 months). Multivariate analysis showed that the rates of underlying disease (P < 0.001) and lymphovascular invasion (P = 0.005) were higher among the 40 patients who died than among the 119 survivors. The overall 3-  and 5-year survival rates were 82.9 % and 77.1 %, respectively; the rates of the patients with lymphovascular invasion were 61.9 % and 42.4 %, respectively, and the rates of patients without lymphovascular invasion were 86.1 % and 81.8 %, respectively (P < 0.001). CONCLUSIONS: Additional treatment provides fewer benefits to patients who do not have long life expectancies. Additional surgery can be considered for patients with lymphovascular invasion because of its high mortality rate; however, the benefits and risks of surgery should be considered carefully.

Contribution of sediment contamination to multi-stress in lowland waters.

Water bodies in densely populated lowland areas are often impacted by multiple stressors. At these multi-stressed sites, it remains challenging to quantify the contribution of contaminated sediments. This study, therefore, aimed to elucidate the contribution of sediment contamination in 16 multi-stressed drainage ditches throughout the Netherlands. To this end an adjusted TRIAD framework was applied, where 1) contaminants and other variables in the sediment and the overlying water were measured, 2) whole-sediment laboratory bioassays were performed using larvae of the non-biting midge Chironomus riparius, and 3) the in situ benthic macroinvertebrate community composition was determined. It was hypothesized that the benthic macroinvertebrate community composition would respond to all jointly present stressors in both water and sediment, whereas the whole-sediment bioassays would only respond to the stressors present in the sediment. The benthic macroinvertebrate community composition was indeed related to multiple stressors in both water and sediment. Taxa richness was positively correlated with the presence of PO4-P in the water, macrophyte cover and some pesticides. Evenness, the number of Trichoptera families and the SPEARpesticides were positively correlated to the C:P ratios in the sediment, whilst negative correlations were observed with various contaminants in both the water and sediment. The whole-sediment bioassays with C. riparius positively related to the nutrient content of the sediment, whereas no negative relations to the sediment-associated contaminants were observed, even though the lowered SPEARpesticides index indicated contaminant effects in the field. Therefore, it was concluded that sediment contamination was identified as one of the various stressors that potentially drove the benthic macroinvertebrate community composition in the multi-stressed drainage ditches, but that nutrients may have masked the adverse effects caused by low and diverse sediment contaminants on C. riparius in the bioassays.

Characteristics of color optical shutter with dye-doped polymer network liquid crystal.

The optical properties and the theoretical prediction of color optical shutter with dye-doped polymer network liquid crystal (PNLC) were investigated. The view-angle dependence of reflectance according to the bias conditions showed distinctive characteristics, which could be explained from the effects of dye absorption and path length. It was also shown that the thickness dependence of reflectance was strongly influenced by the light-scattering coefficient. Our experimental results matched up well with the theoretical prediction based on the light scattering of liquid crystals in polymer network and the absorption of dichroic dye. This work indicates potential to improve the optical device using dye-doped liquid crystal-polymer composite.

Transnasal endoscope-assisted endoscopic submucosal dissection for gastric adenoma and early gastric cancer in the pyloric area: a case series.

Endoscopic submucosal dissection (ESD) is an important therapeutic option for gastric adenoma and early gastric cancer (EGC). However, ESD is technically difficult when lesions are located in the pyloric area. Our aim was to introduce the transnasal endoscope-assisted ESD method, which provides for excellent cutting-line visualization through control of submucosal traction. A total of eight patients with gastric adenoma or EGC located in the pyloric area were consecutively enrolled. A primary operating endoscope was used to perform marking, incision, submucosal dissection, and hemostasis, while a thinner, transnasal endoscope operated by a second endoscopist was used to retract connective submucosal tissue to provide cutting-line visualization using V-shaped grasping forceps. En bloc resection was achieved in all eight cases, as was complete resection. The median longest lesion diameter was 19 mm (range: 12-25 mm), and the median procedure time was 37.5 minutes (range: 29-59 minutes). There were no incidents of significant bleeding or perforation. Transnasal endoscope-assisted ESD was useful for treating gastric neoplasms in the pyloric area. The procedure was relatively easy and safe, provided excellent visualization through tissue retraction, and allowed for complete en bloc resection.

Formation of hybrid structures: copper oxide nanocrystals templated on ultralong copper nanowires for open network sensing at room temperature.

A facile large-scale synthesis approach for producing intrinsically p-type nanowires with uniform coverage of nanocrystals to form a highly interconnected porous nanowire network is of great demand for p-type sensing. Here, we have demonstrated synthesis of a very high aspect ratio (10(2)-10(5)) open network of interconnected hybrid nanocrystals-nanowire copper and copper oxide nanomaterials. The copper nanowire scaffold is employed to realize a porous and highly interconnected network of hybrid metal-metal oxide nanocrystal-nanowire structures. The structural and composition tunability of the hybrid nanomaterials is demonstrated. The hybrid copper-copper oxide nanowires exhibit enhanced gas/light sensing properties without any operating temperature. This may be attributed to enhanced medium diffusion due to the porous network of highly interconnected nanocrystal-nanowire structures.

Association of the interferon-γ gene (CA)n repeat polymorphism with endometriosis.

OBJECTIVE: To investigate whether the interferon-γ (IFN-γ) gene (CA)(n) repeat polymorphism is associated with susceptibility to endometriosis. DESIGN: Case-control study. SETTING: University Department of Obstetrics and Gynaecology. POPULATION: Women with (n = 622) and without (n = 442) endometriosis. METHODS: Genotyping was performed by fluorescent polymerase chain reaction (PCR) and gene-scan analysis. MAIN OUTCOME MEASURES: Genotype distribution and allele frequency of the dinucleotide (CA)(n) repeat polymorphism in the IFN-γ gene. RESULTS: Seven alleles (12-18 repeats) of the IFN-γ gene (CA)(n) repeat polymorphism were found. In both patients with endometriosis and controls the most common allele was composed of 13 repeats, followed by an allele of 15 repeats, and then by an allele of 12 repeats. Patients with endometriosis had a significantly higher incidence of genotypes with alleles composed of fewer repeats (12-13 repeats), compared with the controls (92.0 versus 84.4%, respectively, P < 001). CONCLUSIONS: Our results suggest that the (CA)(n) repeat polymorphism in the IFN-γ gene may be associated with a risk of endometriosis in the South Korean population.

Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.

Leptin, the gene product of the obese gene, may play an important role in regulating body weight by signalling the size of the adipose tissue mass. Plasma leptin was found to be highly correlated with body mass index (BMI) in rodents and in 87 lean and obese humans. In humans, there was variability in plasma leptin at each BMI suggesting that there are differences in its secretion rate from fat. Weight loss due to food restriction was associated with a decrease in plasma leptin in samples from mice and obese humans.