Effect of sleep deprivation on the performance of surgical residents.
Surgical residents were tested under sleep-deprived and nonsleep-deprived conditions. Three performance domains were tested: factual recall, the ability to concentrate, and manual dexterity. Sleep deprivation was defined as less than 3 hours of sleep in a 24 hour period. A randomized, repeated measures design was used. Split-plot analysis of variances was used to analyze the mean scores, and it revealed that there were no significant differences in performance in the sleep-deprived condition compared with performance in the nonsleep-deprived condition in any of the three domains tested. Moderate sleep deprivation appeared to be well tolerated by the surgical residents studied in this investigation.


(Z)-3-Chloro-N-[(Z)-3-(3-chloro-2-methyl-phenyl-imino)-butan-2-yl-idene]-2-methyl-aniline.
In the title compound, C(18)H(18)Cl(2)N(2), the complete molecule is generated by the application of C(2) symmetry. The C=N bond has an E configuration. The dihedral angle between the benzene ring and the 1,4-diaza-butadiene plane is 66.81 (9)°.


Momentary Analysis of Tinnitus: Considering the Patient.
Ecological momentary assessment is a valuable research technique meant to capture real-time data and contextualize disease. While more common in neuropsychiatric research, this methodology is exceptionally fit for tinnitus. Tinnitus has been shown to be affected by many patient-level and environment-specific factors. From an individual's baseline anxiety to the level of ambient noise in their environment, the level of bother experienced by those with tinnitus can vary widely. Only assessing tinnitus within a clinical environment can distort the true impact of the disease. Ecological data can minimize bias while generating an individualistic picture of the burden being experienced by the patient. Individual data can also compliment new research methods rooted in precision medicine, providing clearer, better-suited treatments for each patient on the tinnitus spectrum.


Extracardiac pressure changes do not alter contractile function of the isolated left ventricle.
To determine whether or not extracardiac pressure has an effect on left ventricular contractile function, we analyzed pressure-volume relationships of six isolated, perfused canine hearts in an air-tight chamber. The chamber pressure was set at -60, -30, 0, 30 and 60 mm Hg and left ventricular pressure-volume relationships studied. The slope (Ees) and volume axis intercept (Vo) of the transmural pressure-volume relationship were used to compare the pump functions of an individual heart at the different extracardiac pressures applied. No significant difference in either Ees or Vo was seen with different extracardiac pressures. During isovolumic ventricular contraction, developed left ventricular pressure did not change over the range of extracardiac pressures applied. The same was true during ejecting contraction; when the downstream pressure of the computer simulated afterload circuit and the venous filling pressure of the preload circuit were changed in parallel with the extracardiac pressure, pressure-volume loops remained identical throughout their course for all of the extracardiac pressures applied. We conclude that transmural pressure is the overwhelmingly dominant loading factor governing LV contraction, and myocardial contractile function is unaffected by the absolute value of extracardiac pressure.


Molecular mechanisms mediating lymphocyte recirculation, inflammation, and metastasis formation.
A multitude of glycoproteins expressed in cellular membranes have been identified by monoclonal antibodies. Besides mediating transient cell/cell contacts, these molecules unequivocally function as receptor structures capable of transmitting signals for cell growth and differentiation. They are the central determinators of local immune responses, and they allow an adjustment of the recirculating immunocompetent cells to their respective local microenvironments. Given that receptor/ligand interactions are characteristic of particular in vivo sites, knowledge of structural and functional features of adhesion receptors can provide new prospects for a more targeted clinical immune intervention.


Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome.
The main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population. Patients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome. In total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p<0.001), extra-thyroidal extension (HR 24.95; p<0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p<0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease. We present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.


Please turn off the lights: the effectiveness of visual prompts.
Two early studies showed that visual prompts can be effectively used to encourage people to turn off the lights in unoccupied classrooms, but they were methodologically limited. The current study used an ABAB-B design with an 11-week follow-up to investigate whether two different visual prompts (large and small signs) could be employed to increase "lights off" behaviour in 17 unoccupied washrooms. The odds were eight times higher that lights would be turned off in washrooms with signs than washrooms without, and large signs trended toward being more effective than small signs. Signs in washrooms with windows appeared to be the most effective, but this finding merits further research. Behaviour change persisted throughout the follow-up period, but reactance by a single washroom user resulted in some signs being removed. Compared to previous research, the current study used an improved methodology with a larger number of study sites. This study demonstrated that a simple, well-designed sign can effectively encourage energy conservation.


Anterior cervical plating technique to prevent adjacent-level ossification development.
The proximity (<5 mm) of the plate to the adjacent disc space is known to be a critical risk factor for adjacent-level ossification development (ALOD). As plates provide many advantages including higher fusion rates and improved alignment, their use will continue. Instead, it is necessary to modify the plating techniques to minimize this complication. To determine if our newer plating technique decreases the incidence of ALOD after anterior cervical plating. Retrospective matched cohort analysis of preoperative and postoperative radiographic data. One hundred patients were classified into two groups; conventional (C) and new (N) plating techniques. The control group (Group C) was matched to the study group (Group N) in a 1:1 fashion using matching criteria of age (within 5 years), gender, number of fusion levels, and comorbidities, including diabetes and tobacco use. The lateral plain X-rays of cervical spine taken at postoperative 6 months and 2 years were used for analysis. In Group N, the cranial and caudal screws were started at the anterior end plate corners and angled away from the end plates so as to use the shortest possible plate and maximize the distance to the adjacent end plates. Group C was the historical control using a longer plate with more orthogonal screw angulation. On postoperative 6-week lateral films, the distances from the tip of the plate to both cranial and caudal adjacent discs (plate-to-disc distances) were measured. Based on the postoperative 2-year radiographs, the incidence of ALOD was determined, and the severity of ossification was classified on a scale ranging from Grade 0 (no ossification) to Grade 3 (complete bridging). Mean plate-to-disc distances in Group N were significantly longer at both cranial and caudal adjacent levels than those in Group C (p<.001). The incidence of ALOD was significantly lower in Group N than in Group C, both at the cranial adjacent disc spaces (42% vs. 72%) and caudal adjacent disc spaces (20% vs. 42%) (p<.05). Severe ossification (Grade 2 or greater) also developed less frequently in Group N at cranial and caudal levels (6% vs. 20%, respectively; p<.05). The new technique of using a shorter plate with longer angulated screws resulted in significantly reduced incidence and severity of ALOD.


Pregnane glycosides from the antidepressant active fraction of cultivated Cynanchum otophyllum.
Based on the bioactive screening results, four new pregnane glycosides, namely cynanotophyllosides A-D (1-4) were isolated from the anti-depressant active fraction of cultivated Cynanchum otophyllum, along with thirteen known compounds (5-17). The new compounds were characterized as qingyangshengenin 3-O-β-D-glucopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (1), qingyangshengenin-3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-α-L-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (2), caudatin-3-O-β-D-glucopyranosyl-(1→4)-β-D-thevetopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-digitoxopyranoside (3) caudatin-3-O-β-D-glucopyranosyl -(1→4)-β-D-thevetopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (4), by detailed spectroscopic analysis and acidic hydrolysis.


Conditions required for induction of murine p30 by herpes simplex virus.
Mouse cells (line N cIA cl10) contain 1.2-2.5 ng murine leukaemia virus (MuLV) p30 antigen/mg of protein; this amount of antigen is measurable by competition radioimmunoassay (RIA) but is not detectable by indirect immunofluorescence (IF). Infection of N cIA cl10 cells with herpes simplex virus type 2 (HSV-2) induces expression of MuLV p30. Induction by HSV-2 does not require either cell or virus DNA synthesis and is optimal 8 h post infection when cells at 50-70% confluence are infected at a multiplicity of infection (MOI) of 5-8 PFU/cell. At an MOI of 2.5, 70-80% of the cells express HSV antigens while none of the cells express p30; at an MOI of 5.0, 70-80% of the cells express HSV antigens but 55% of the cells express p30. Using the conditions reported in this paper for preparation of competing antigen, induction of p30 by HSV-2 (strain 333) infection is not measurable by competition RIA.


Modelling bacterial transmission in human allergen-specific IgE sensitization.
The impact of bacterial transmission from mother to child on human allergy development is poorly understood. The aim of the present work was therefore to use a temporal collected dataset of 117 mothers and their children to model the potential effect of mother-to-child bacterial transmission on allergy (IgE) sensitization. We have recently shown a negative IgE correlation to high Escherichia coli levels until the age of 1 year, with a shift to positive correlation to high Bacteroides fragilis levels at the age of 2. In the present work, we used the previous published data to model the persistence and interaction effects of E. coli and B. fragilis with respect to IgE sensitization. Temporal modelling was made by first defining a stochastic model for sensitization state based on Markov chains and regression tree analyses. Subsequent simulations were used to determine the impact of mother-to-infant bacterial transmission. The regression tree analyses showed that E. coli colonization within 4 days was negatively correlated to sensitization, while lack of E. coli colonization at day 4 combined with B. fragilis colonization after 4 months was positively correlated. With Markov chain analyses, we found that E. coli was highly persistent in infants until the age of 4 months, while the persistence of B. fragilis increased with age. Simulations showed that the mother's bacterial composition correlated significantly to the child's IgE sensitization state at the age of 2 years. High E. coli and low B. fragilis levels in the mother were negatively correlated, while low E. coli and high B. fragilis were positively correlated to IgE. Our results support that allergy could partly be communicable, being transferred from mother to infant through the gut microbiota.


Gut microbiota modulation in Alzheimer's disease: Focus on lipid metabolism.
Alzheimer's disease (AD) and age-related dementias represent a major and increasing global health challenge. Unhealthy diet and lifestyle can unbalance the intestinal microbiota composition and, consequently energy metabolism, contributing to AD pathogenesis. Impairment of cerebral cholesterol metabolism occurs in both aging and AD, and lipid-lowering agents have been associated to a lower risk of neurodegenerative diseases, but the link between blood lipid profile and AD remains a matter of debate. Recently, probiotics have emerged as a promising and safe strategy to manipulate gut microbiota composition and increase the host health status through a multi-level mechanism that is currently under investigation. Specifically, oral supplementation with a multi-strain probiotic formulation (SLAB51) reduced amyloid beta aggregates and brain damages in a triple transgenic mouse model of AD (3xTg-AD). Treated mice showed improved cognitive functions in response to an enrichment of gut anti-inflammatory metabolites, increased plasma concentrations of neuroprotective gut hormones, and ameliorated glucose uptake and metabolism. This work focuses on the evaluation of the effects of SLAB51 chronic administration on lipid metabolism in 3xTg-AD mice and the respective wild-type counterpart. On this purpose, 8 weeks old mice were orally administered with SLAB51 for 4 and 12 months to analyze the plasma lipid profile (using lipidomic analyses and enzymatic colorimetric assays), along with the cerebral and hepatic expression levels of key regulators of cholesterol metabolism (through Western blotting and ELISA). Upon probiotics administration, cholesterol biosynthesis was inhibited in AD mice with a process involving sterol regulatory element binding protein 1c and liver X receptors mediated pathways. Decreased plasma and brain concentration of 27-hydroxycholesterol and increased brain expression of cholesterol 24S-hydroxylase indicated that alternative pathways of bile acid synthesis are influenced. The plasmatic increase of arachidonic acid in treated AD mice reflects dynamic interactions among several actors of a complex inflammatory response, in which polyunsaturated fatty acids can compete each other and simultaneously co-operate in the resolution of inflammation. These evidence, together with the hypocholesterolemic effects, the ameliorated fatty acids profile and the decreased omega 6/omega 3 ratio successfully demonstrated that microbiota modulation through probiotics can positively change lipid composition in AD mice, with arachidonic acid representing one important hub metabolite in the interactions among probiotic-induced lipid profile changes, insulin sensitivity, and inflammation.


High-density Association Mapping and Interaction Analysis of PLA2R1 and HLA Regions with Idiopathic Membranous Nephropathy in Japanese.
Although recent studies showed anti-PLA2R antibody plays a crucial role in idiopathic membranous nephropathy (IMN), detailed HLA mapping and interaction between the HLA genes and PLA2R1 have not been investigated in IMN. We genotyped across the PLA2R1 gene and the HLA region, using 183 IMN patients and 811 healthy controls. Five SNPs around the PLA2R1 gene were significantly associated with IMN. In addition to the two SNPs previously reported to be strongly associated with IMN, rs3749119 and rs35771982 (OR 3.02 and 2.93, P = 3.24E-14 and 4.64E-14, respectively), two novel intronic SNPs (rs2715928 and rs16844715) were also identified as IMN-associated SNPs (OR = 2.30 and 2.51, P = 3.15E-10 and 5.66E-13, respectively). In the HLA gene analysis, DRB1*1501 and DQB1*0602 were strongly associated with IMN (P = 1.14E-11 and 1.25E-11, respectively). The interaction was strongest between HLA-DRB1*15:01 - HLA-DQB1*06:02 and the intronic SNP rs2715928 (OR = 17.53, P = 4.26E-26). Furthermore, positive interaction was also observed between HLA-DRB1*15:01 - HLA-DQB1*06:02 and the missense SNP rs35771982 (OR = 15.91, P = 2.76E-29), which is in strong linkage disequilibrium with 5'UTR SNP rs3749119, and intronic SNP rs16844715 (OR = 15.91, P = 2.30E-26) for IMN. Neither HLA-DRB1*15:01 nor HLA-DQB1*06:02 was associated with steroid responsiveness, overall survival and renal survival during the observation period of mean 11 years though limited number of analysis.


Altered pain sensitivity in 5×familial Alzheimer disease mice is associated with dendritic spine loss in anterior cingulate cortex pyramidal neurons.
Chronic pain is highly prevalent. Individuals with cognitive disorders such as Alzheimer disease are a susceptible population in which pain is frequently difficult to diagnosis. It is still unclear whether the pathological changes in patients with Alzheimer disease will affect pain processing. Here, we leverage animal behavior, neural activity recording, optogenetics, chemogenetics, and Alzheimer disease modeling to examine the contribution of the anterior cingulate cortex (ACC) neurons to pain response. The 5× familial Alzheimer disease mice show alleviated mechanical allodynia which can be regained by the genetic activation of ACC excitatory neurons. Furthermore, the lower peak neuronal excitation, delayed response initiation, as well as the dendritic spine reduction of ACC pyramidal neurons in 5×familial Alzheimer disease mice can be mimicked by Rac1 or actin polymerization inhibitor in wild-type (WT) mice. These findings indicate that abnormal of pain sensitivity in Alzheimer disease modeling mice is closely related to the variation of neuronal activity and dendritic spine loss in ACC pyramidal neurons, suggesting the crucial role of dendritic spine density in pain processing.


Propylene Glycol and Maize Grain Supplementation Improve Fertility Parameters in Dairy Cows.
The aim of the study was to determine the effect of propylene glycol and maize grain content by-pass starch supplementation during the transition period and the first 56 days of lactation on blood metabolic indices, milk production and fertility parameters in dairy cows. Seventy-five Polish Holstein-Friesian dairy cows were assigned to treatment 21 days before calving. The treatments included: TG-2.5 kg triticale grain/cow per day supplemented from 14 days prepartum to day 56 postpartum, PG-2.5 kg triticale grain/cow per day supplemented from day 14 before parturition to day 56 postpartum, and 400 g propylene glycol/cow per day from 14 days prepartum to 14 days of lactation and MG-2.5 kg maize grain/cow per day supplemented from day 14 before parturition to day 56 postpartum. PG and MG had an effect resulting in the highest glucose concentration at 28 d of lactation. Cows assigned to the PG and MG groups had significantly higher cholesterol levels confronted with TG group at day 14 of lactation, while at days 28 and 56 the same difference was observed only between the MG and TG groups. PG had an effect on shortening the period to first ovulation. PG and MG improved the first service conception rate and decreased the number of services per conception in cows. In conclusion, both treatments of dairy cows with PG and MG improved their fertility parameters, while they had a slight effect on their metabolic profile and no effect on their milking performance.


Expression enhancement of bubaline somatotropin in E. coli through gene modifications in the 5'-end coding region.
This study addresses the problem of poor expression of somatotropin (ST) gene in E. coli and describes expression enhancement through silent and non-silent gene modifications. A series of constructs with codon optimization, substitution, deletion or addition in the 5'-region of the sequence encoding bubaline ST (BbST) were prepared. In the native form, the BbST expression was barely discernible on SDS-gel of the total E. coli cellular proteins (TCP). Introduction of silent and non-silent mutations in +2 to +8 codons, however, raised the expression levels to varying extents. In some constructs, a single base variation, i.e., G-->A or G-->C led to a remarkable increase in BbST expression (up to 28% of the TCP) whereas in the case of G-->T substitution the expression dropped to undetectable levels. Deletion of native GCC codon and addition of CAUCAC repeat thrice at +2 position enhanced the expression up to 48%, while insertion of NGG codons at the same position caused just a modest increase in expression. Differences in expression appeared as if related to the nature of early downstream codons (especially +2) and the stability of mRNA secondary structure although the levels of intracellular mRNA pools, as analyzed by real-time RT-PCR were quite similar. Overall, the study highlights the importance of 5'-end codon adaptations in solving the problems encountered in expressing the eukaryotic genes in E. coli.


Genetic investigation in an Italian child with an unusual association of atrial septal defect, attributable to a new familial GATA4 gene mutation, and neonatal diabetes due to pancreatic agenesis.
Permanent neonatal diabetes is a rare condition affecting 1 in 300,000-400,000 live births; only in 60% of cases it is possible to identify the genetic defect. The condition of pancreatic agenesis is rarer still. Only two genes are known to determine this phenotype: PDX-1 and PTF1A. Congenital heart defects are among the most common developmental anomalies, affecting 1% of newborns, and the GATA4 gene is less frequently involved in these disorders. An Italian child with pancreatic agenesis and an atrial septal defect was genetically investigated to elucidate whether the association of the two pathologies was casual, or represented a new pancreatic/cardiac syndrome. A panel of pancreas development genes, including GCK, Kir6.2, PTF1A, PDX-1, HNF-1A, NgN3, SOX17, SOX7, SOX9, INS, HNF1-B and SUR1 plus the GATA4 gene, were screened for characterization of pancreatic agenesis and cardiac defect. Screening for genes causing permanent neonatal diabetes was negative. A novel mutation in GATA4 (c1512C>T) was detected and functional characterization confirmed a reduced activity of the protein. In the family members, the GATA4 mutation co-segregates with a cardiac phenotype, but not with pancreatic agenesis. We describe the first report of pancretic agenesis with an associated cardiac defect and a mutation in the GATA4 gene. We could not establish that the GATA4 mutation was causative for pancreatic agenesis and further genetic investigation to detect the genetic cause of the pancreas agenesis was unsuccessful. We conclude that, the two pathologies are attributable to two independent events.


Neural modulation of cutaneous differentiation: epidermal hyperplasia and precocious hair development following partial neuralectomy in opossum pups.
The original intent of the present study was to evaluate the compensatory response of the nervous system to areas of denervation. A portion of the spinal cord in the lumbosacral region of one-day opossum pups (Monodelphis domesticus) was removed by cauterization. This partial neuralectomy produced an expected compensatory response of neurons in the dorsal root ganglia, but in addition produced unexpected abnormalities of cutaneous differentiation. At 4-6 days following surgery, an increase in the thickness of the epidermis resembling glabrous palmar or plantar skin was seen. This hyperplastic epidermis appeared to be associated with an abnormally dense innervation of the dermis and epidermis. Eight days following partial neuralectomy most animals showed areas of precocious hair development. Nerve fibers were always seen in the dermis associated with these precocious hairs and were seen to penetrate the basal lamina in the region of the epidermal-hair shaft boundary. These results imply a critical role for afferent nerves in the normal development of the skin and its appendages.


A network meta-analysis of the short-term efficacy of five chemotherapy regimens based on cisplatin and fluorouracil for esophagogastric junctional adenocarcinoma.
The primary purpose of this study was to explore the short-term efficacy of different cisplatin and fluorouracil-based chemotherapy regimens in the treatment of patients with esophagogastric junctional adenocarcinoma (EGJA) using a network meta-analysis (NMA). Randomized controlled trials (RCTs) related to chemotherapy regimens based on cisplatin and fluorouracil for EGJA were included from the PubMed, EMBASE and Cochrane Library electronic databases (from inception to June 2016). Direct and indirect evidence were combined to calculate the pooled odds ratio (OR) and its 95% confidence interval (95% CI) as well as to draw the surface under the cumulative ranking (SUCRA) curves. This NMA finally enrolled ten eligible RCTs with the following five regimens: cisplatin plus fluorouracil (cisplatin+fluorouracil), cisplatin+fluorouracil-based chemotherapy (cisplatin+fluorouracil+docetaxel/epirubicin/irinotecan), fluorouracil-based chemotherapy (fluorouracil+docetaxel/doxorubicin/methotrexate/irinotecan), cisplatin-based chemotherapy (cisplatin+docetaxel/epirubicin/irinotecan/capecitabine/s-1) and other drug-based chemotherapy (docetaxel/irinotecan/capecitabine). These results revealed that compared with a cisplatin+ fluorouracil-based chemotherapy regimen, the fluorouracil-based chemotherapy regimen had a lower overall response rate (ORR) and partial response (PR) for EGJA patients (ORR: OR=0.43, 95% CI=0.22-0.86; PR: OR=0.46, 95% CI=0.23-0.91). Cluster analyses suggested that the cisplatin+fluorouracil-based chemotherapy regimen had the best short-term efficacy for EGJA in terms of the complete response (CR), PR, ORR, stable disease (SD) and progression disease (PD). Our results indicated that cisplatin+fluorouracil-based chemotherapy regimens may have the best short-term efficacy in the treatment of EGJA.


Altered phenotype and function of dendritic cells in individuals with chronic periodontitis.
To investigate the effects of periodontal bacterial lysates on maturation and function of mature monocyte-derived dendritic cells (m-MDDCs) derived from individuals with chronic periodontitis (CP) or healthy periodontal tissue (HP). m-MDDCs derived from peripheral blood monocytes, cultured for 7 days in presence of interleukin (IL)-4 and granulocyte-macrophage colony stimulating factor (GM-CSF), were stimulated with lysates of Streptococcus sanguinis, Prevotella intermedia, Porphyromonas gingivalis, or Treponema denticola on day 4, and were then phenotyped. IL-10, IL-12 and IFN-gamma concentration in the supernatant of cultures were measured. Expression of HLA-DR was lower in bacterial-unstimulated mature m-MDDC from CP compared to HP (p=0.04), while expression of CD1a and CD123 were higher in CP. The expression pattern of HLA-DR, CD11c, CD123, and CD1a did not change on bacterial stimulation, regardless of the bacteria. Stimulation with P. intermedia upregulated CD80 and CD86 in CP cells (p≤0.05). Production of IL-12p70 by bacterial-unstimulated m-MDDCs was 5.8-fold greater in CP compared to HP. Bacterial stimulation further increased IL-12p70 production while decreasing IL-10. Significantly more IFN-gamma was produced in co-cultures of CP m-MDDCs than with HP m-MDDCs when cells were stimulated with P. intermedia (p=0.009). Bacterial-unstimulated m-MDDC from CP exhibited a more immature phenotype but a cytokine profile biased towards proinflammatory response; this pattern was maintained/exacerbated after bacterial stimulation. P. intermedia upregulated co-stimulatory molecules and IFN-gamma expression in CP m-MDDC. These events might contribute to periodontitis pathogenesis.


Novel, thapsigargin-insensitive intracellular Ca(2+) stores control growth hormone release from goldfish pituitary cells.
The relative contribution of intracellular Ca(2+) stores to basal and agonist-stimulated hormone release in pituitary cells is still not well understood, especially in non-mammalian vertebrates. Using ratiometric Ca(2+) imaging of single identified goldfish somatotropes, along with time-resolved measurements of growth hormone (GH) secretion, we investigated the Ca(2+)-dependent signal transduction of two endogenous regulators of GH release from the goldfish pituitary. Two gonadotropin-releasing hormones (sGnRH and cGnRH-II) initiated GH release in nominally Ca(2+) free conditions. GnRH-evoked GH release was additive to KCl-stimulated GH responses. Ca(2+) signals and GH release elicited by both GnRHs were abolished by pretreatment with TMB-8, which blocks the release of Ca(2+) from intracellular stores. GnRH-stimulated GH secretion is mediated by caffeine-sensitive intracellular Ca(2+) stores that are functionally independent from those sensitive to thapsigargin and other inhibitors of SERCA-type Ca(2+)/ATPases. The caffeine/TMB-8-sensitive Ca(2+) stores are also involved in spontaneous Ca(2+) signalling and the maintenance of prolonged GH release.


Heterotopic pregnancy.
A 35-year-old woman presented to the emergency department with abdominal pain 36 hours after a therapeutic abortion. A positive pregnancy test was thought to be related to the recently terminated intrauterine gestation. The patient was admitted for observation. When monitoring revealed intraabdominal hemorrhage, exploratory surgery was performed and a ruptured tubal pregnancy discovered. The patient recovered uneventfully. The incidence, predisposing factors, and diagnosis of simultaneous intrauterine and extrauterine pregnancy are discussed.


Susceptibility to different tick genera in Gambian N'Dama and Gobra zebu cattle exposed to naturally occurring tick infestations.
Tick collection on one side of the body and whole tail was performed weekly over one year on 11 Gambian N'Dama (Bos taurus) and 11 Gobra zebu (Bos indicus) cattle to assess breed susceptibility to naturally occurring ticks. Enzyme-linked immunosorbant assay was also performed to assess the serological prevalence of Anaplasma marginale antigen and Babesia bigemina antibody. Packed red cell volume was measured and liveweight gain was recorded. Significantly higher numbers of Amblyomma variegatum (P < 0.002) and Hyalomma spp. (P < 0.001) were found on Gobra zebu than on N'Dama cattle. The serological prevalence of A. marginale antigen was significantly (P < 0.001) lower in N'Dama breed, whilst no difference in the serological prevalence of B. bigemina antibody was found between N'Dama and Gobra cattle. Packed red cell volume was negatively affected by A. marginale infection in both breeds, but to a lesser extent in N'Dama cattle. Liveweight gain was significantly (P < 0.003) higher in N'Dama in comparison with Gobra cattle during the period of abundance of A. variegatum and Hyalomma spp. adults. The significantly lower burdens of A. variegatum and Hyalomma spp. ticks in Gambian N'Dama in comparison with Gobra zebu cattle confirms previous findings. It also shows a more deleterious effect of ticks and tick-borne diseases on animal production and health in Gobra zebu than in N'Dama cattle. The presence of a tick resistant trait in N'Dama cattle is suggested.


Resynchronization improves reproductive efficiency of suckled Bos taurus beef cows subjected to spring-summer or autumn-winter breeding season in South Brazil.
The objective of the present study was to evaluate the effect of estrus resynchronization (RE) after the first Timed Artificial Insemination (TAI) protocol on reproductive efficiency of suckled Bos taurus beef cows (n = 1052; Angus and Brangus) subjected to two different breeding season (BS) in Rio Grande do Sul, Brazil. In experiment 1, cows were maintained in native pasture on conventional BS (spring-summer), and in experiment 2, cows were maintained in a grazing area cultivated in an integrated crop-livestock system on modified BS (autumn -winter). Experiment 1 cows (n = 92) were randomly distributed in two reproductive managements: 1) TAI at the first day of the BS (Day 0), followed by natural service (NS) on day 10 until the end of the BS (TAI + NS; n = 45) or, 2) TAI on day 0, followed by RE 22 days after the first TAI and then followed by NS on day 42 until the end of the BS (TAI + RE22 + NS; n = 47). Experiment 2 cows (n = 960) were subjected to one of four reproductive managements: 1) only NS for 90 days of the BS (NS; n = 266); 2) TAI on day 0, followed by NS on day 10 until the end of the BS (TAI + NS; n = 200); 3) TAI on day 0, followed by RE 22 days after the first TAI and then followed by NS on day 42 until the end of the BS (TAI + RE22 + NS; n = 249) or, 4) TAI on day 0, followed by RE 30 days after the first TAI and then followed by NS on day 50 until the end of the BS (TAI + RE30 + NS; n = 245). In experiment 1, conception rate after first TAI was similar for treatments TAI + NS (42%, 19/45) and TAI + RE22 + NS (48%, 23/47; P = 0.4107). Total pregnancy rates at day 60 of the BS were 55.6% and 66.6% for TAI + NS and TAI + RE22 + NS, respectively (P = 0.006). In experiment 2, only 3% of the females submitted to NS were pregnant 30 days after the onset of BS, a lower rate compared to other groups (TAI + NS = 40%; TAI + RE22 + NS = 39.8%; TAI + RE30 + NS = 40%; P < 0.001). At 70 days of the BS, the groups TAI + RE22 + NS and TAI + RE30 + NS obtained greater pregnancy rate (66.3% and 69.4%, respectively) than other groups (NS = 16.9%; TAI + NS = 48%; P < 0.001). Pregnancy rate at the end of BS was greater in RE groups (TAI + RE22 + NS = 81.5%; TAI + RE30 + NS = 83.7%) than the NS (45.1%) or TAI + NS (71%). In conclusion, resynchronization increases pregnancy rate per AI (P/AI) and reproductive efficiency of suckled Bos taurus beef cows during spring-summer or autumn-winter breeding season in natural pasture or cultivated pasture, respectively.


Feasibility and Safety of Adopting Next-Day Discharge as First-Line Option After Transfemoral Transcatheter Aortic Valve Replacement.
Data on next-day discharge (NDD) after transcatheter aortic valve replacement (TAVR) are limited. This study investigated the feasibility and safety of NDD as a first-line option (the very-early discharge [VED] strategy) compared with the early-discharge (ED) strategy (2-3 days as a first-line option) after TAVR. We reviewed 611 consecutive patients who had minimalist TAVR (transfemoral approach under conscious sedation) and no in-hospital mortality; a total of 418 patients underwent ED strategy (since December 2013) and 193 patients underwent VED strategy (as part of a hospital initiative to reduce length of stay, since August 2016). NDD in the VED strategy was performed with heart team consensus in patients without significant complications. The primary outcome was a composite of 30-day all-cause mortality/rehospitalization. Sixty-five patients (33.7%) in the VED strategy and 10 patients (2.4%) in the ED strategy were discharged the next day (P<.001). NDD patients had received balloon-expandable (n = 30) or self-expanding valves (n = 45) and showed a similar primary outcome rate compared with non-NDD patients. After adjustment using propensity score matching (172 pairs), post-TAVR length of stay was significantly shorter in the VED group (3.2 ± 3.1 days) than in the ED group (3.5 ± 2.7 days; P<.01). The primary outcome did not differ between the two groups (7.0% vs 11.6%; P=.14), with comparable 30-day mortality rate (1.2% vs 2.3%; P=.68) and rehospitalization rate (5.8% vs 11.1%; P=.08). Utilization of NDD as a first-line option after minimalist TAVR is feasible and safe, and leads to further reduction in length of stay compared with an ED strategy.


First detection of Echinococcus multilocularis in Bosnia and Herzegovina.
Echinococcus multilocularis has been spreading through Central Eastern Europe but has not yet been reported in Bosnia and Herzegovina (B&H). Recently, this parasite is confirmed in Croatia suggesting the movement of the parasite's distribution limit further south. Given that there is no surveillance or monitoring system for echinococcosis in B&H, our study was designed as a pilot study of E. multilocularis. A total of 57 red foxes originating from 24 localities all over the country were collected during the routine rabies monitoring, autopsied and examined for the presence of echinococcosis. Based on intestinal scraping technique and microscopy, E. multilocularis adult worms have been detected in one (1/57, 1.75%) red fox. To verify this finding and to differentiate Echinococcus spp., DNA extracted from adult worms was subjected to species-specific PCR targeting part of the mitochondrial 12S ribosomal RNA gene. E. multilocularis PCR-positive samples were further confirmed by NGS sequencing of a 203 bp amplified fragment of 12S rRNA, which has been deposited in GenBank (Accession no.: OP047920). This finding represents the first detection of E. multilocularis in B&H, strongly suggesting its presence in the country. The confirmation of the parasite in the same locality where migrants/refugees temporarily stay on their route to Western Europe highlights the need for a One Health approach in addressing all future questions. Moreover, the first detection of E. multilocularis in B&H warrants the need for the implementation of an appropriate state surveillance program.


Benchmarking the post-accreditation patient safety culture at King Abdulaziz University Hospital.
Accreditation is an internationally recognized evaluation process used to assess, promote, and guarantee efficient and effective patient care and safety. Saudi Arabia is one of the first countries in the eastern Mediterranean region to implement health care accreditation standards. This study provides valuable information pertaining to the impact of accreditation in the unique multicultural, multilingual competitive environment at King Abdulaziz University Hospital in Saudi Arabia. The objective of this study was to perform an unbiased assessment of the impact of accreditation on patient safety culture. Cross-sectional retrospective and prospective study post-accreditation at King Abdulaziz University Hospital in Jeddah, Saudi Arabia from January 1, 2006 to December 31, 2009. A total of 870 registered nurses from eight different cultural backgrounds working at 22 hospital units were given electronic access to the survey. A 5-point Likert scale was used, ranging from 1 for 'Strongly disagree' to 5 for 'Strongly agree.' The survey results were matched with the international benchmarks from the Hospital Survey on Patient Safety Culture, 2005. A total of 605 nurses answered the survey questionnaire. The comparison between the percentages of nurses at King Abdulaziz University Hospital (KAUH) and those at international hospitals who answered 'Agree' and 'Strongly agree' showed a post-accreditation improved perception of the culture of patient safety. Accreditation has an overall statistically significant improvement in the perception of the culture of patient safety.


Evaluation of Qualitative Magnetic Resonance Imaging Features for Diagnosis of Chronic Pancreatitis.
The purpose of this study was to determine qualitative pancreatic magnetic resonance imaging (MRI) features that must be present to predict abnormal pancreatic secretory function in patients evaluated for chronic pancreatitis (CP). The MRIs of study subjects were reviewed by 2 abdominal radiologists; qualitative parenchyma and ductal features were recorded. Endoscopic pancreatic function test (ePFT) results (reference standard) were classified as normal (peak pancreatic fluid bicarbonate [HCO3-] ≥75 meq/L) or abnormal (<75). Abnormal ePFT was further classified as mild/moderate (74-65) and marked deficiency (<65). Statistical analysis was performed to assess the association between MRI features and abnormal ePFT. The study cohort was composed of 93 subjects, mean age 49 years (range, 18-78 years), 65% females. Univariate analysis identified 9 qualitative MRI features significantly (P < 0.05) associated with abnormal pancreatic secretory function. Number of MRI features increases as peak pancreatic fluid [HCO3-] decreases (Pearson r = -0.629; P = 0.001). Receiver operating characteristic curve analysis determined that a threshold of 6 or more associated MRI features 64% sensitive and 94% specific for marked bicarbonate deficiency. Qualitative MRI parenchymal and ductal features are associated with CP. Presence of 6 or more features results in a higher specificity for the diagnosis of CP in advanced disease.


Health & Wealth: is weight loss success related to monetary savings in U.S. adults of low-income? Findings from a National Study.
Many individuals aspire to attain various goals in life, such as committing to a healthful diet to slim down or saving for retirement to enhance future welfare. While these behaviors (weight loss and saving) share the common denominator of self-regulation, it is unclear whether success in one domain is related to the other. Therefore, we examined the relationship between long term weight loss (LTWL) success and monetary savings among U.S. adults who at one point in life diverged from normal weight status. Data on 1994 adults with a maximum BMI ≥ 25 kg/m2 and with an annual household income equal or less than 200% poverty level. Data were derived from a U.S. population-based study (NHANES). The independent variable was LTWL success (loss maintained for at least 1 year), which was operationalized as < 10% (reference group), 10.00-19.99%, and ≥ 20.00%. The dependent variable was monetary savings (e.g., 401 K), defined as a 3-category ordinal variable. We employed ordered logistic regression to estimate the relationship between LTWL success and increased odds for higher overall savings. Multivariable analysis revealed that adjusting for income, education and other covariates, being in the highest LTWL category (≥20.00%) significantly reduced the likelihood of monetary savings in comparison to the reference group (OR = 0.55, 95%CI = 0.34-0.91). This relationship was not observed in the lower LTWL category (10.00-19.99%). Adults who in the past were overweight or obese and who presently exhibit high levels of LTWL, were markedly less successful when it came to their finances. This might stem from significant cognitive-affective resources exerted during the weight loss process coupled with a paucity of financial resources which impede financial decision making. This supposition, however, warrants future research.


Congenital lobar emphysema resulting from bronchial sling around a normal right main pulmonary artery.
A 5-month-old female infant was transferred to our institution for evaluation of recurrent upper respiratory tract symptoms and chest x-ray films showing hyperaeration of the right upper lobe. Preoperative studies including chest fluoroscopy, lung scan, and bronchoscopy suggested congenital lobar emphysema. At thoracotomy, an anomalous right upper lobe bronchus which bifurcated around the main pulmonary artery in a sling fashion was found. This anatomic abnormality has not been described previously and is a unique cause of congenital lobar emphysema.


Visual habituation tasks: the role of infant temperament.
This longitudinal study investigated the relation between infant temperament and dropout rate in two visual habituation tasks when infants (N=80) were 6 and 12 months of age. At both age points, infant temperament was assessed with the Infant Behavior Questionnaire Revised (IBQ-R) and infants were presented with the same two habituation tasks that were similar in set-up and procedure but different in content. Consistent with previous German work, a two-factor solution was found at each age point indicating Surgency/Extraversion and Negative Affectivity as underlying temperament dimensions. Dropout rates in the habituation tasks ranged from 21% to 68%. Overall, only few IBQ-R subscales, especially Duration of Orienting, had an impact on dropout rate. This suggests that the relatively high dropout rates reported in infant looking time studies are not systematically related to infant temperament. However, findings also suggest that temperament might have an impact on the likelihood of dropout when a habituation task is conducted at the end of a longer test session.


Caloric intake, stress, and menstrual function in athletes.
The cause of menstrual disturbance in athletes is still debated. Apart from the acute and chronic effects of exertion, other associated behavioral variables are suspected to play a key role. A longitudinal study with frequent blood sampling was undertaken to link information about nutrition and stress with a quantitative assessment of endocrine menstrual function in 18 endurance-trained athletes and 25 age-matched, nonathletic women. Four athletes did not show hormonal signs of follicular development. The 14 athletes with cyclic gonadal function did not differ from controls with regard to estradiol concentrations during the follicular phase and at midcycle. During the luteal phase, however, they showed significantly reduced areas under the estradiol and progesterone curves. Caloric intake, as assessed by nutritional diaries, correlated positively with the area under the progesterone curve during the luteal phase (rs = 0.70, P less than 0.01). Ratings of subjective stress in the area "partner, family, friends" correlated negatively with the luteal progesterone area (rs = 0.80; P less than 0.01). Data support the hypothesis that nutrition and stress may play a critical role in the genesis of menstrual disturbance in athletes.


Unusual characteristics of ciliate actins.
Actin is a cytoskeletal protein that is ubiquitous in eukaryotes, hence the corresponding genes and proteins have been isolated from numerous organisms as different as animals, plants, fungi and protozoa. Several atomic models are available for the monomeric as well as the filamentous form, and more than 70 proteins that bind actin and control filament dynamics have been isolated from diverse eukaryotes. Moreover, the function and dynamics of the actin cytoskeleton in several eukaryotic systems have been depicted in depth. Unlike other protozoa, such as amoeba, actin is not an abundant protein in ciliates, whose cytoskeleton is mainly composed of microtubular arrays. Ciliate actin has been studied in several species, and it was established early on that this ciliate protein is very different from that of other eukaryotes. Similarly, the actin-binding proteins studied in ciliates display great differences with those of other eukaryotes. Consequently, ciliate actin has been considered as "unconventional," and this review focuses on molecular data leading to this conclusion.


Tackle the free radicals damage in COVID-19.
COVID-19 is a severe pandemic which has caused a devastating amount of loss in lives around the world, and yet we still don't know how to appropriately treat this disease. We know very little about the pathogenesis of SARS-CoV-2, the virus which induces the COVID-19. However, COVID-19 does share many similar symptoms with SARS and influenza. Previous scientific discoveries learned from lab animal models and clinical practices shed light on possible pathogenic mechanisms in COVID-19. In the past decades, accumulated scientific findings confirmed the pathogenic role of free radicals damage in respiratory virus infection. Astonishingly very few medical professionals mention the crucial role of free radical damage in COVID-19. This hypothesis aims to summarize the crucial pathogenic role of free radical damage in respiratory virus induced pneumonia and suggest an antioxidative therapeutic strategy for COVID-19.


On the action of vitamin C on the neuromuscular junctions.
High concentrations of ascorbic acid produce complete blockage of the transmission of nervous stimuli on the isolated neuromuscular preparation of phrenic nerve-hemidiaphragm of the rat.


An Expanded Multi-scale Monte Carlo Simulation Method for Personalized Radiobiological Effect Estimation in Radiotherapy: a feasibility study.
A novel and versatile "bottom-up" approach is developed to estimate the radiobiological effect of clinic radiotherapy. The model consists of multi-scale Monte Carlo simulations from organ to cell levels. At cellular level, accumulated damages are computed using a spectrum-based accumulation algorithm and predefined cellular damage database. The damage repair mechanism is modeled by an expanded reaction-rate two-lesion kinetic model, which were calibrated through replicating a radiobiological experiment. Multi-scale modeling is then performed on a lung cancer patient under conventional fractionated irradiation. The cell killing effects of two representative voxels (isocenter and peripheral voxel of the tumor) are computed and compared. At microscopic level, the nucleus dose and damage yields vary among all nucleuses within the voxels. Slightly larger percentage of cDSB yield is observed for the peripheral voxel (55.0%) compared to the isocenter one (52.5%). For isocenter voxel, survival fraction increase monotonically at reduced oxygen environment. Under an extreme anoxic condition (0.001%), survival fraction is calculated to be 80% and the hypoxia reduction factor reaches a maximum value of 2.24. In conclusion, with biological-related variations, the proposed multi-scale approach is more versatile than the existing approaches for evaluating personalized radiobiological effects in radiotherapy.


Experimental and theoretical laser-Doppler frequency spectra of a tissuelike model of a human head with capillaries.
Laser-Doppler flow measurements with penetration depths from 10 to 30 mm have been performed on a layered model of the human head consisting of a regular array of capillaries with diameters of 340 microm embedded in an epoxy matrix with tissuelike scattering and absorption properties. Monte Carlo simulations and an analytical approach based on diffusing wave spectroscopy have corroborated the measurements and have led to a quantitative description of flow in deep-lying tissue layers with regard to layers near the surface also. The results indicate that it may be possible to measure changes in cortical blood flow even in the presence of a well-perfused scalp.


Correlation Analyses Between Childhood Behavioral Disturbance and Maternal Alexithymia: An Observational Study.
Caregivers' responses have an impact on children's emotional and behavioral development. The inability of caregivers to perceive their own emotions affects their responses to children. This study aims to examine the relationship between a mother's difficulties in emotional expression and children's emotional and behavioral disorders. A total of 78 cases, aged between 3 and 15 years old, were included in this study. The mothers completed the Taiwan version of the "Toronto Alexithymia Scale" (TAS) and "Children's Behavior Checklist" (CBCL) questionnaires, which served as research tools. TAS consists of three factors: difficulty in distinguishing emotions (Factor 1, F1), difficulty in expressing feelings (Factor 2, F2), and an externally oriented thinking style (Factor 3, F3). CBCL represents a child's behavior profile. The Mann-Whitney test and correlation analyses were used for follow-up analysis. Our analysis revealed that F1, F2, F3, and total scores of TAS (TAS-Total) correlate positively with the somatic complaint subscale of CBCL (F1: p = 0.003; F2: p = 0.002; F3: p = 0.034, TAS-Total p=0.002). Additionally, TAS-F1 was positively correlated with the internalizing problems subscale of CBCL (p = 0.020) and the withdrawn (WD) subscale of CBCL (p = 0.044). We also found a significant association between TAS-F1 and WD of CBCL in boys alone (p = 0.022). However, we observed a negative association between TAS-F3 and the social problems subscale of CBCL in boys alone (p = 0.038). Mothers with alexithymic features are more likely to have children who internalize emotions, leading to withdrawal and somatic expression. Boys tend to exhibit withdrawal traits associated with internalization. This study provides initial evidence of a partial correlation between maternal alexithymia and children's emotional and behavioral disorders, emphasizing the importance of investigating caregivers' emotional traits for a better understanding of children's development in the future.


Unintended consequences of United States chronic pain guidelines.
In 2015, the United States of America (USA) Department of Health and Human Services (HHS) released an issue brief that addressed opioid addiction, opioid overdoses, and opioid-related deaths as a public health concern within the country. After collaboration with state and stakeholder organizations, the HHS identified three target initiatives aimed to mitigate the negative consequences of opioid use within the USA. One initiative included implementation of guidelines to help reduce inappropriate opioid prescribing with a goal to reduce morbidity and mortality. The aim of this commentary is to discuss the misapplication and unintended consequences of the USA CDC Guideline for Prescribing Opioids for Chronic Pain.


Research on religion and serious mental illness.
According to this review, religion plays a largely positive role in mental health; future research on severe mental disorders should include religious factors more directly.


Enhanced echo intensity in vastus medialis is associated with worsening of functional disabilities and symptoms in patients with knee osteoarthritis: a 3 years longitudinal study.
Patients with knee osteoarthritis (OA) experience muscle quality loss, and is characterized by the enhanced echo intensity (EI) of the vastus medialis (VM) muscles and a high extracellular water-to-intracellular water (ECW/ICW) ratio of the thigh. This study aimed to elucidate the association between muscle degeneration and the worsening of functional disabilities and symptoms in patients with KOA over 3 years duration. Thirty-three patients with KOA who completed follow-up over 3 years were included in the analysis. The knee scoring system (KSS) was used to evaluate the functional abilities and symptoms. Based on the 3 years change in KSS scores, patients were classified into progressive or non-progressive groups. Muscle thickness (MT) and EI of the VM were determined using ultrasonography. The ECW/ICW ratio was measured using segmental-bioelectrical impedance spectroscopy. Multivariable logistic regression analyses were conducted with the groups as the dependent variables and VM-MT, VM-EI, and ECW/ICW ratio at baseline as independent variables, including potential confounders. Thirteen (39.4%) patients showed progressive features. VM-EI at baseline was significantly associated with the progression of functional disabilities (adjusted odds ratio [OR] 1.24; 95% confidence interval [CI] 1.03 - 1.50) and symptoms (adjusted OR 1.13; 95% CI 1.01 - 1.25). Enhanced VM-EI was associated with the worsening of functional disabilities and symptoms in patients with KOA over a period of 3 years. Therefore, the assessment of VM-EI using ultrasonography is a useful indicator for predicting the future worsening of KOA.


Mesopancreas in pancreatic cancer: where do we stand - review of literature.
Pancreatic cancer is associated with poor prognosis and surgery remains the main modality of treatment. Negative resection margin is an important prognostic factor for survival. Retropancreatic margin or the medial margin is the most common site of positive resection margin. Mesopancreas was proposed in analogy with mesorectum, which is considered as a fusion fascia formed embryologically during the development of pancreas. This mesopancreas lies posterior to the pancreas and contains pancreaticoduodenal vessels, lymphatics, nerve plexus and loose areolar tissue. Various technical modifications were proposed for better dissection of mesopancreas like posterior approach and artery first approach. There is an increased rate of R0 resection by these technical modifications but whether this will turn to increase in survival rates is yet to be established.


[Clinical considerations concerning a new case of laryngeal chondroma].
A new case of a chondroma of the larynx is reported discussing the diagnosis and its treatment. Also a brief review of the literature is presented. Scattered calcification observed by CT is considered as a pathognomic finding. Finally, biopsy is the only method for establishing the positive diagnosis.


Association Between Common Variants of APOE, ABCA7, A2M, BACE1, and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease: Data from the PUMCH Dementia Cohort.
The previous studies have identified several genes in relation to Alzheimer's disease (AD), such as ABCA7, CR1, etc. A few studies have explored the association between the common variants, mainly in the non-coding regions of these genes, and cerebrospinal fluid (CSF) biomarkers. Fewer studies target the variants in the coding regions. To illustrate the association between the common variants within or adjacent to the coding regions of AD susceptible genes and CSF biomarkers in AD patients. 75 sporadic probable AD patients were extracted from the dementia cohort of Peking Union Medical College Hospital. They all had history inquiry, physical examination, blood test, cognitive assessment, brain MRI, CSF testing of Aβ42, 181p-tau, and t-tau, and next-generation DNA sequencing. Sixty-nine common single nucleotide polymorphisms (SNPs) (minor allele frequency > 0.01) within or near the coding region of 13 AD susceptible genes were included in the analysis. The rs7412-CC (APOE) genotype showed lower CSF Aβ42 level and higher p-tau/Aβ42 ratio than the rs7412-CT genotype. The rs3752246-C (ABCA7) allele correlated with lower CSF Aβ42 level. The alternate alleles of six ABCA7 SNPs were related to lower CSF p-tau, including rs3745842, rs3764648, rs3764652, rs4147930, rs4147934 and rs881768. The rs11609582-TT (A2M) genotype showed higher CSF p-tau than the rs11609582-TA genotype. The p-tau/Aβ42 ratio was higher in the rs490460-TT (BACE1) genotype relative to the rs490460-GT genotype. Some common variants within or near the coding regions of APOE, ABCA7, A2M, and BACE1 are associated with CSF Aβ42, p-tau. or p-tau/Aβ42.


A confirmatory factor analysis of the Pain Catastrophizing Scale: invariant factor structure across clinical and non-clinical populations.
This study examined the factor structure of the Pain Catastrophizing Scale in three different Dutch-speaking samples: 550 pain-free students, 162 chronic low back pain patients, and 100 fibromyalgia patients. Confirmatory factor analyses were used to compare three different models of pain catastrophizing (one factor, two oblique factors, three oblique factors), and to investigate the invariance of the factor structure across the three different samples. The results indicated that a three-factor oblique model with a four-item rumination factor, a three-item magnification factor, and a six-item helplessness factor provided the best fit to the data in the three samples. Furthermore, it was found that this model could be considered as invariant across three samples (pain-free students, chronic low back pain patients, and fibromyalgia patients) and across gender, indicating that the same processes are measured in different subgroups.


TNFalpha antagonist therapy in ankylosing spondylitis and psoriatic arthritis: recommendations of the French Society for Rheumatology.
To develop recommendations for TNFalpha antagonist therapy in patients with spondyloarthropathies. The Delphi consensus procedure was used to select questions, to which evidence-based answers were sought in the literature. Expert opinion was used when needed to estimate the risks and benefits of TNFalpha antagonists. TNFalpha antagonists exert potent antiinflammatory effects but fail to provide a definitive cure. Recommendations were developed for patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA). The following criteria for TNFalpha antagonist therapy were selected: definitive diagnosis of AS or PsA, active disease for at least 4 consecutive weeks documented during two physician visits, overall physician's assessment of disease activity>/=4/10 and BASDAI>/=4/10 in axial disease or at least three tender and swollen joints in peripheral disease, failure to respond adequately to at least three nonsteroidal antiinflammatory drugs given in optimal dosages for at least 3 months in axial disease or at least one disease-modifying antirheumatic drug (methotrexate, leflunomide, sulfasalazine) for at least 4 months, with local glucocorticoid injections if appropriate, in peripheral disease. Effectiveness and safety should be evaluated by a rheumatologist. The frequency of monitoring depends on the drug. Lack of effectiveness should be defined as inadequate improvement after 6-12 weeks, with a less than two-point decrease in the BASDAI in axial disease or a less than 30% decrease in the tender and swollen joint counts in peripheral disease. These clinical practice recommendations should help rheumatologists in their everyday decisions regarding the use of TNFalpha antagonist therapy in patients with AS or PsA.


The minipig as a new model for the evaluation of doxorubicin-induced chronic toxicity.
Doxorubicin can cause life-threatening toxic effects in several organs, with cardiotoxicity being the major concern. Although a large number of animal models have been utilized to study doxorubicin toxicity, several restrictions limit their use. Since the Göttingen minipig is an accepted species for non-clinical safety assessment and translation to man, we aimed at exploring its use as a non-rodent animal model for safety assessment and regulatory toxicity studies using doxorubicin. Three groups of three males and three females adult Göttingen minipigs received 1.5 mg kg(-1) , 3/2.3 mg kg(-1) or vehicle at intervals of 3 weeks for 7 cycles. Doxorubicin treatment resulted in a dose-related decrease in the erythrocytes, hemoglobin and hematocrit count, accompanied by leukopenia and thrombocytopenia. Bone marrow smears revealed dose-related hypocellularity. Urea and creatinine levels were elevated in treated animals, associated with proteinuria and hematuria. Histopathological evaluation detected nephropathy and atrophy of hematopoietic tissues/organs, mucosa of the intestinal tract and male genital tract. Cardiac lesions including chronic inflammation, endocardial hyperplasia, hemorrhage and myxomatous changes were evident in hematoxylin and eosin stains, and evaluation of semi-thin sections showed the presence of dose-related vacuolation in the atrial and ventricular cardiomyocytes. Cardiac troponin levels were increased in the high-dose group, but there was no direct correlation to the severity of the histopathological lesions. This study confirms that the Göttingen minipig has a comparable toxicity profile to humans and considering its anatomical, physiological, genetic and biochemical resemblance to humans, it should be considered as the non-rodent species of choice for studies on doxorubicin toxicity. Copyright © 2015 John Wiley & Sons, Ltd.


Chemical characterization and biological activity of essential oils from Daucus carota L. subsp. carota growing wild on the Mediterranean coast and on the Atlantic coast.
The essential oils and supercritical CO(2) extracts of wild Daucus carota L. subsp. carota growing spontaneously in Sardinia and in Portugal were investigated. The main components in the Sardinian essential oil of flowering and mature umbels with seeds are beta-bisabolene (17.6-51.0%) and 11-alpha-(H)-himachal-4-en-1-beta-ol (9.0-21.6%); instead, the oils from Portuguese samples are predominantly composed of geranyl acetate (5.2-65.0%) and alpha-pinene (3.5-37.9%). Supercritical extracts contain lower amounts of monoterpenes and higher amounts of sesquiterpene hydrocarbons. Antifungal activities of the Sardinian oils were the highest, particularly for dermatophytes and Cryptococcus neoformans, with MIC values of 0.16-0.64 microL mL(-1).


Contemporary management of patients with heart failure.
Treatment of patients with heart failure has become extremely challenging. A complicated interplay of myocardial, hemodynamic, and humoral factors marking this condition requires a delicate balancing of medication use, procedural intervention, and lifestyle changes. Judicious prescription of therapies in stepwise fashion as the syndrome severity worsens (Fig. 2) is critical to success.


Complementary anti-inflammatory effects of a β-blocker and a corticosteroid in an asthma model.
Glucocorticosteroids are the mainstay treatment for chronic asthma; however, adverse effects can limit their usefulness. We previously determined in experimental asthma that chronic administration of β₂-adrenoceptor inverse agonists reduced airway hyperresponsiveness and indexes of inflammation. However, the effect of co-administration of glucocorticosteroids with β₂-adrenoceptor inverse agonists is unknown. Therefore, we evaluated the anti-inflammatory effect of co-administration of dexamethasone, a glucocorticosteroid, and nadolol, a β₂-inverse agonist, in a murine asthma model. We measured eosinophils and cytokines in bronchoalveolar lavage fluid and mucin content in epithelial cells after exposure to different concentrations of dexamethasone and nadolol. Dexamethasone was administered for 3 days and nadolol for 24 days prior to ovalbumin challenge. Both drugs were continued during five daily intranasal challenges with ovalbumin. Independent administration of dexamethasone (0.4 mg/kg/day) or nadolol (25 ppm) reduced bronchoalveolar lavage eosinophils by 58% and 36%, respectively (P < 0.05). Co-administration of both drugs yielded an additive reduction in eosinophils (81%, P < 0.05). Co-administration of both drugs (dexamethasone 0.4 mg/kg/day and nadolol 25 ppm) also yielded a greater reduction in mucin volume density (83%) than either drug alone (18% for dexamethasone and 62% for nadolol) and greater than high-dose dexamethasone (71%) alone (P < 0.05). Similarly, co-administration of both drugs (dexamethasone 0.4 mg/kg/day and nadolol 25 ppm) yielded an additive effect on the reduction of type 2 cytokines in bronchoalveolar lavage fluid equivalent to the administration of a 10-fold higher dose of dexamethasone. In Summary, the simultaneous administration of a glucocorticosteroid and a β₂-adrenoceptor inverse agonist was more effective at reducing indexes of airway inflammation than either drug given alone; suggesting nadolol may possess "glucocorticoid-sparing" properties.


GEORCC recommendations on target volumes in radiotherapy for Head Neck Cancer of Unkown Primary.
Head Neck Cancer of Unknown Primary (HNCUP) is a rare condition, representing approximately 5-10% of all head neck cancers. Radiotherapy, adjuvant or radical, is usually employed in the treatment of those patients. To date, no specific guidelines for the optimal definition of the target volume to be irradiated have been published. In recent years, there have been advances in the knowledge of the molecular biology of HNCUP, its diagnostic imaging and the implementation of sophisticated radiotherapy techniques with enhanced precision in target localization and treatment delivery. These progresses have provided valuable information about the natural history of HNCUP that will allow for establishment of the best treatment for each patient, including standardized, consistent and reproducible target volumes definitions. Several recommendations regarding how to choose volumes when contouring HNCUP in clinical practice are reported, in order to achieve a high rate of loco-regional control while avoiding unnecessary toxicity.


Percutaneous radial artery access for peripheral vascular interventions is a safe alternative for upper extremity access.
Percutaneous radial artery access has been increasingly used for peripheral vascular interventions (PVIs). Our goal was to characterize the practice patterns and perioperative outcomes among patients treated using PVI performed via radial artery access. The Vascular Quality Initiative was queried from 2016 to 2020 for PVI performed via upper extremity access. Univariable and multivariable analyses were used to evaluate the periprocedure outcomes of radial artery access cases. A separate sample of brachial artery access cases was used as a comparator. A total of 520 radial artery access cases were identified. The mean age was 69 ± 10 years, and 41.3% were women. Most procedures were performed in the hospital outpatient setting (71.7%). The sheath size was ≤5F for 10%, 6F for 78%, and 7F for 12%. Ultrasound-guided access and protamine were used in 68.3% and 17.3% of cases, respectively. The interventions were aortoiliac (55%), femoropopliteal (55%), and infrapopliteal (9%). Stenting and atherectomy were performed in 55% and 19% of cases, respectively, and more often with 7F sheaths. Access site complications were any hematoma (4.8%), including hematomas resulting in intervention (0.8%), pseudoaneurysms (1%), and access stenosis or occlusion (0.8%). On multivariable analysis, sheath size was not associated with access site complications. Percutaneous brachial artery access (n = 1135) compared with radial access was independently associated with more overall hematomas (odds ratio, 1.73; 95% confidence interval, 1.06-2.81; P = .03). However, access type was not associated with hematomas resulting in intervention (odds ratio, 2.15; 95% confidence interval, 0.69-6.72; P = .19). PVIs via radial artery access exhibited a low prevalence of postprocedural access site complications and were associated with fewer minor hematoma complications compared with interventions performed using brachial artery access. Radial artery access compared with brachial artery access should be the preferred technique for PVIs.


Analysis of basement membrane structure and inflammation during the development of esophageal squamous cell carcinoma in the Chinese Chaoshan high risk region.
To investigate relationships between basement membrane structure, inflammation, beta1 integrin expression, activation of ERK/MAPK signaling pathways, and cell proliferation in esophageal mucosa at various stages during the evolution of esophageal squamous cell carcinoma. Three tissue arrays were made of 228 tissue cores from 428 surgically-resected specimens. The arrays included 26 samples of normal epithelium, 28 with hyperplasia, 18 with dysplasia, 27 with carcinoma in situ and 129 with invasive carcinoma. In addition, 21 cases of hyperplasia, 13 cases of dysplasia and 13 case of carcinoma in situ were obtained by manual microdissection of unfixed frozen tissue. Hematoxylin and eosin stained sections were used to evaluate the epithelium and inflammation. The periodic acid-Schiff stain and an immunohistochemical stain for laminin were used to examine the structure of basement membranes. The expression of beta1 integrin, p-ERK, and Ki67 were evaluated by quantitative immunohistochemistry. RT-PCR and Western blots were also used to detect expression of beta1 integrin. Quantitative scales were developed to classify basement membrane structure and inflammation. Basement membrane alterations correlated with the degree of epithelial change (chi2 = 501.9, p < 0.01) and with the degree of lymphocytic infiltration in the lamina propria and epithelium (chi2 = 273.4, p < 0.01). There was a significant relationship between the extent of basement membrane alteration and the expression of beta1 integrin, p-ERK, and Ki67. The correlations suggest that there is a direct relationship between basement membrane structure and the development of esophageal squamous cell carcinoma.


Topical Low Dose Preservative-Free Hydrocortisone Reduces Signs and Symptoms in Patients with Chronic Dry Eye: A Randomized Clinical Trial.
Dry eye disease (DED) is a highly prevalent ocular condition with a significant burden on affected patients. Regardless of the underlying etiology, DED is associated with increased ocular surface inflammation. We investigated the safety and efficacy of a short-term treatment with topical low dose hydrocortisone in patients with chronic DED and ocular surface inflammation. A total of 60 patients (mean age 51 ± 14 years) with chronic DED and conjunctival hyperemia greater than grade 2 on the Efron scale were included. Patients were randomized to receive either preservative-free hydrocortisone 0.335% (Softacort, Laboratories Thea, France) for 12 days four times daily followed by 2 days twice daily instillation (intense treatment group) or 8 days three times daily followed by 3 days twice daily treatment (standard treatment group). Ocular redness was assessed at baseline, day 14, and day 28. Measurement of intraocular pressure (IOP) and clinical tests to assess signs and symptoms of DED were performed. Conjunctival hyperemia and Ocular Surface Disease Index (OSDI) significantly decreased in both treatment groups (p < 0.001 each) after hydrocortisone treatment. A significant increase in tear film thickness was seen 4 weeks after treatment start (p = 0.03 and p = 0.04, respectively). IOP did not change in either of the two treatment groups (p = 0.45). Treatment with low dose hydrocortisone 0.335% reduced ocular inflammation and decreased OSDI score. No change in IOP was observed in either of the two treatment schedules. Because of its good safety profile, low dose hydrocortisone may be an interesting alternative to standard corticosteroid treatment in DED. Laboratories Thea. Clinicaltrials.gov registry: NCT03907865.


Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-β/Smads pathway.
Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. Astragalus membranaceus (Fisch.) Bunge was widely used in Chinese traditional medicine and showed cardiac protective effects in previous researches. Astragaloside IV(ASG), which is regarded as the most important ingredient of Astragalus, has been showed the effect of cardiac protection via various mechanisms, while no data suggested its action related to miRNAs regulation. The objective of this article is to investigate the inhibition effect of ASG on cardiac fibrosis through the miR-135a-TRPM7-TGF-β/Smads pathway. We extracted the active components from herb according to the paper and measured the content of ASG from the mixture via HPLC. The inhibition potency of cardiac hypertrophy between total extract of Astragalus and ASG was compared. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, ASG (10 mg/kg/d) and Astragalus extract (AE) (4.35 g/kg/d, which contained about ASG 10 mg) were given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 μM) and treated with ASG (10 μM) simultaneously for 24 h. The results showed that both AE and ASG treatment reduced the TRPM7 expression from the gene level and inhibited cardiac fibrosis. ASG group showed similar potency as the AE mixture. ASG treatment significantly decreased the current, mRNA and protein expression of TRPM7 which was one of targets of miR-135a. The activation of TGF-β/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, our results showed that there was a positive feedback between the activation of TGF-β/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis. AE had the effect of cardiac fibrosis inhibition and decreased the mRNA expression of TRPM7. ASG, as one of the effective ingredients of AE, showed the same potency when given the same dose. ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-β/Smads pathway.


Coexisting cancers with atypical glandular abnormalities by liquid-based cytology: A retrospective study in tertiary hospital in a high cervical cancer incident country.
To determine the incidence of coexisting cancers in women with glandular cell abnormalities detected from liquid-based cytology and to compare the detection rate of premalignant and malignant lesions among various subtypes of glandular cell abnormalities. From January 2014 to December 2016, liquid-based cytology was performed in 85,517 women. Using the Bethesda system 2001 criteria, abnormal cervical cytology was diagnosed in 3650 women (4.3%). Glandular cell abnormalities were diagnosed in 110 women (0.13%). Ten women with pre-existing genital tract cancers and 13 women who lost to follow up were excluded. Clinical characteristic, colposcopic finding, and histopathological data were reviewed in 87 women. High-grade premalignant and malignant lesions were diagnosed in 34 patients (39.1%). Co-existing cancer was diagnosed in 31 patients (35.6%); 15 cervical cancers (17.2%) and 16 endometrial cancers (18.4%). The detection rate of significant lesions (CIN2+ or malignant lesions) in patients with AGC-NOS was 14.9%, AGC-FN was 38.9% and AIS/adenocarcinoma was 90.9% (p < 0.001). Glandular cell abnormalities associated with high incidence of coexisting endometrial and cervical cancers. Comprehensive genital tract screening to evaluate gynecologic malignancy is strongly recommended in all women with glandular cell abnormalities.


In-hospital efficacy of endovascular aortic repair in patients with impending rupture versus contained rupture of abdominal aortic aneurysms.
The purpose of our study was to compare the efficacy of endovascular aortic repair (EVAR) in patients with impending rupture of abdominal aortic aneurysm (IRAAA) versus contained rupture of abdominal aortic aneurysm (CRAAA). Of the 21 patients who underwent EVAR for infrarenal AAA from January 2009 to May 2011, 11 did so for IRAAA and 10 for CRAAA. We compared their demographic and aneurysmal characteristics, comorbidities, complications, and clinical outcomes during hospitalization. The CRAAA group was younger than the IRAAA group. There were no group differences in AAA size, operation time, volume of contrast agent, length of hospital stay (LOHS), or preoperative LOHS. A small difference in mean intraoperative blood loss of ∼4 mL was noted, but was recognized as clinically insignificant. ICU stay and postoperative LOHS were greater in the CRAAA than in the IRAAA. One patient in the IRAAA group had a mild headache after EVAR. Four patients in the CRAAA group had postoperative complications: 1 had acute renal dysfunction; 1 had retroperitoneal infection; 1 had respiratory failure and myocardial infarction; and 1 died of respiratory tract infection and respiratory and cardiac failure. Patients undergoing EVAR for CRAAA have a higher incidence of postprocedural severe complications and death than patients undergoing EVAR for IRAAA.


Multiple levels of visual object constancy revealed by event-related fMRI of repetition priming.
We conducted two event-related functional magnetic resonance imaging (fMRI) experiments to investigate the neural substrates of visual object recognition in humans. We used a repetition-priming method with visual stimuli recurring at unpredictable intervals, either with the same appearance or with changes in size, viewpoint or exemplar. Lateral occipital and posterior inferior temporal cortex showed lower activity for repetitions of both real and non-sense objects; fusiform and left inferior frontal regions showed decreases for repetitions of only real objects. Repetition of different exemplars with the same name affected only the left inferior frontal cortex. Crucially, priming-induced decreases in activity of the right fusiform cortex depended on whether the three-dimensional objects were repeated with the same viewpoint, regardless of whether retinal image size changed; left fusiform decreases were independent of both viewpoint and size. These data show that dissociable subsystems in ventral visual cortex maintain distinct view-dependent and view-invariant object representations.


Ocular responses evoked by capsaicin and prostaglandin E2 are inhibited by a substance P antagonist.
Injection of capsaicin or prostaglandin E2 into the vitreous chamber of the rabbit eye resulted in miosis and breakdown of the blood-aqueous barrier, manifested in aqueous flare. Pretreatment with the neuronal blocker tetrodotoxin or the substance P antagonist (D-Pro, D-Trp)-SP greatly reduced the ocular responses to capsaicin and prostaglandin E2. The results suggest a role for neuronal substance P in the ocular response to injury.


Correction: A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer.
[This corrects the article DOI: 10.1371/journal.pone.0253021.].


Dental caries disparities in early childhood: A study of kindergarten children in British Columbia.
The objective of this paper was to describe results of a public health-administered, provincial dental survey of children aged 4-6 years old in British Columbia, and assess the changes in rates of dental caries geographically and by neighbourhood socio-economic status between baseline (2006/07) and follow-up data collection (2009/10). The study design involved two retrospective cohorts of kindergarten children who received a public health-administered dental assessment in the years 2006/07 and 2009/10. Neighbourhood socio-economic status was measured by an index created from Canadian Census and Tax Filer data sets. The dental outcomes included previous decay experience, untreated visible decay, and urgent treatment needs. The analysis comprised dental outcomes for 35,602 kindergarten children in 2006/07 and 35,215 children in 2009/10. There was a modest decrease in dental decay rates between surveys, with rates of decay experience - previous and untreated - of 38.9% and 36.7% respectively. However, there were disparities, with almost 50% of children with dental decay in the most socio-economically disadvantaged neighbourhoods, and approximately 30% with dental decay in the least disadvantaged areas. The kindergarten dental survey had extensive coverage, was at the population level, and enabled analysis of change in early childhood dental decay rates over time and by geography. Although overall rates improved, dental health inequalities persisted in both survey years at both regional and neighbourhood levels.


Oxidation-induced nanolite crystallization triggered the 2021 eruption of Fukutoku-Oka-no-Ba, Japan.
Nanometer-sized crystals (nanolites) play an important role in controlling eruptions by affecting the viscosity of magmas and inducing bubble nucleation. We present detailed microscopic and nanoscopic petrographic analyses of nanolite-bearing and nanolite-free pumice from the 2021 eruption of Fukutoku-Oka-no-Ba, Japan. The nanolite mineral assemblage includes biotite, which is absent from the phenocryst mineral assemblage, and magnetite and clinopyroxene, which are observed as phenocrysts. The boundary between the nanolite-bearing brown glass and nanolite-free colorless glass is either sharp or gradational, and the sharp boundaries also appear sharp under the transmitted electron microscope. X-ray absorption fine structure (XAFS) analysis of the volcanic glass revealed that the nanolite-free colorless glass records an oxygen fugacity of QFM + 0.98 (log units), whereas the nanolite-bearing brown glass records a higher apparent oxygen fugacity (~ QFM + 2). Thermodynamic modelling using MELTS indicates that higher oxygen fugacities increase the liquidus temperature and thus induced the crystallization of magnetite nanolites. The hydrous nanolite mineral assemblage and glass oxygen fugacity estimates suggest that an oxidizing fluid supplied by a hot mafic magma induced nanolite crystallization in the magma reservoir, before the magma fragmentation. The oxidation-induced nanolite crystallization then enhanced heterogeneous bubble nucleation, resulting in convection in the magma reservoir and triggering the eruption.


Synthesis, α-glucosidase inhibition and in silico studies of some 4-(5-fluoro-2-substituted-1H-benzimidazol-6-yl)morpholine derivatives.
In this study, a new series of 4-(5-fluoro-2-substituted-1H-benzimidazol-6-yl)morpholine derivatives has been synthesized and screened for their α-glucosidase inhibitory potential. All molecules showed a considerable α-glucosidase inhibitory potential with IC50 values ranging from 20.46 ± 0.21 to 0.18 ± 0.01 µg/mL when compared with the acarbose (IC50 = 8.16 ± 0.12 µg/mL) as the standard. Compound 4 k having methoxy group on phenyl ring had the highest inhibitory effect with IC50 = 0.18 ± 0.01 µg/mL value among the examined compounds. Electron-donating groups such as methyl and methoxy on the phenyl ring played an important role in the inhibition. Also, the Lineweaver-Burk plots analysis displayed that the inhibition type of 4k was the competitive mode like acarbose as standard. In silico studies were also performed to explore the binding interaction of the most active compound.


Clinicopathological features of cryoglobulinemic glomerulonephritis associated with HBV infection: a retrospective analysis of 8 cases in China.
We retrospectively analyzed clinicopathologic features of 8 cases of hepatitis B virus-associated glomerulonephritis with hyaline thrombi, to confirm the diagnosis of cryoglobulinemic glomerulonephritis (CRYGN) associated with HBV infection. Retrospective analysis was carried out with demographic information, clinical manifestations, laboratory parameters, pathological and prognostic features. The median age of 8 patients was 30.5 years (range, 21-75 years), including 6 males and 2 femles (M:F = 3:1). One patient had Raynaud's syndrome. Cryoglobulin testing was performed in 4 cases of our series, and 3 cases had elevated cryocrit (>256). Serum C4 decreased in all detected cases. Histopathologically, all cases showed hyaline thrombi occluded in capillary lumina; Co-deposit of IgG, IgM, IgA, Fib, C3d, C4d, C1q, HBsAg and HBcAb were identified in hyaline deposit/hyaline thrombi with polyclonal Igκ and Igλ staining. Ultrastructural examination confirmed the hyaline thrombi to be huge electron-dense bodies, which were a homogeneous texture. The results suggest that 8 cases in the series are CRYGN associated with HBV infection. The incidence of CRYGN associated HBV was extremely low. Our series suggested that prognosis of CRYGN associated HBV was better in patients with mild symptoms, but it was poor in elder patients with severe vasculitis.


Enamel Surface Morphology: An Ultrastructural Comparative Study of Anterior and Posterior Permanent Teeth.
Enamel is one of the most important structures of the tooth, both functionally and aesthetically. Because of the highly mineralized nature of enamel, its structure is difficult to study under routine light microscopy. Since scanning electron microscopy (SEM) offers the possibility of studying structures under very high magnification without altering the gross specimen, it is one of the best methods to study the enamel surface. To study and compare the surface morphology and morphometry of enamel on various surfaces of permanent dentition. A total of 20 permanent teeth were analyzed under the SEM. In both anterior and posterior teeth, four surfaces - mesial, distal, labial, and lingual - in three thirds - cervical, middle, and incisal - were studied. In addition, the occlusal surface was also studied for the posterior teeth. The different prism morphology and prism dimensions were recorded. Based on our observations, we could definitely identify striae of retzius, debris, and cracks under ×50 magnification. Three morphological patterns of prism arrangement were identified: Type 1 - shallow prisms, Type 2 - well-defined prisms, Type 3 - microporosities, on analyzing the mesial, distal, labial, lingual, and occlusal surfaces of the permanent teeth, at ×3000 magnification. The prisms were measured under ×6000 magnification and the results showed larger prisms in posterior than in anterior teeth. The study aided us in categorizing the enamel prism structure based on morphology and morphometry in anterior and posterior teeth of the permanent dentition.


Clinical significance of isolated abnormal intestinal findings in magnetic resonance enterography in patients with suspected small bowel disease.
Magnetic resonance imaging (MRE) is a well-established adjunct diagnostic tool for the diagnosis of Crohn's Disease (CD), as ileocolonoscopy can sometimes be falsely reassuring when CD skips distal terminal ileum. We aimed to determine the frequency and clinical significance of isolated abnormal small bowel findings in MRE with normal ileal view in ileoscopy. We retrospectively reviewed findings from 1611 MRE studies that were conducted between 2012 and 2018 to detect patients bearing abnormal intestinal findings and having full ileocolonoscopy. After exclusion of normal or repetitive MRE scans and previously known CD, 147 patients with abnormal MRE detected. MRE scans were categorized as suspicious of CD and non-specific findings. Out of 147 patients with abnormal MRE, 122 (83%) had terminal ileum involvement in MRE consistent with ileoscopy findings. Twenty-five (17%) patients were found to have solitarily abnormal intestinal findings in MRE with normal ileoscopy. Only 3 (12%) were diagnosed with CD initially, and all had MRE findings suspicious of CD. The remainder 40% (n = 10) were diagnosed with non-Crohn's small bowel disease after further investigation, while in the other 48% (n = 12) abnormal MRE findings could not be explained with any organic disease in the follow-up. The present study demonstrated that only a small portion of patients with isolated abnormal intestinal findings in MRE is CD, and more than that are non-crohn's small bowel diseases. These findings, even if they carry the suspicion of CD, do not transform to CD in the long-term follow-up.


Sialyl Lewis X-polysaccharide conjugates: targeting inflammatory lesions.
A novel system for active targeting of inflammatory lesions has been established. A SLeX-CMPul conjugate (2) showed accumulation that was 2.5-fold higher in inflammatory lesions in vivo than a SLN-CMPul conjugate (4) and 300-fold higher than monovalent SLeX (6).


The generalization of deferred imitation in enculturated chimpanzees (Pan troglodytes).
Deferred imitation of object-related actions and generalization of imitation to similar but not identical tasks was assessed in three human-reared (enculturated) chimpanzees, ranging in age from 5 to 9 years. Each ape displayed high levels of deferred imitation and only slightly lower levels of generalization of imitation. The youngest two chimpanzees were more apt to generalize the model's actions when they had displayed portions of the target behaviors at baseline, consistent with the idea that learning is more likely to occur when working within the "zone of proximal development." We argue that generalization of imitation is the best evidence to date of imitative learning in chimpanzees.


Complementary therapies in the management of low back pain: a survey of reflexologists.
To investigate current management of low back pain (LBP) by reflexologists. A postal survey of reflexologists (n=500) sampled from the International Institute of Reflexology. The questionnaire used investigated a range of areas including: professional details, reflexology training and practice, views and experiences of reflexology, reflexology and LBP, and views on other complementary therapies. Response rate was 49.6% (n=248). The majority of respondents were female (95%), and were primarily employed within another profession such as nursing or teaching. Respondents perceived reflexology to have a positive effect on relieving LBP (94.3%) and to provide more benefit than simply relaxation. Practitioners also commented on other treatment effects, e.g. improving sleep patterns, decreasing anxiety and stress. It was reported that other healthcare practitioners, including general practitioners, referred patients to reflexologists for treatment. Respondents considered reflexology to be an effective therapy for LBP. Further work is warranted to investigate the potential role of such treatment in the management of this prevalent and intractable condition.


Uterine sarcoma 2008.
Uterine sarcomas are a group of rare and usually aggressive soft tissue cancers. They have a wide range of histologic appearances, from myomatous to osteous to stromal. The three major subtypes of uterine sarcomas (listed in decreasing order of incidence) are carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma. Most patients with uterine sarcomas are middle- to older-aged women who present with abnormal uterine bleeding or pelvic mass, which may be confused with leiomyoma. Surgery--including hysterectomy and resection of disease--serves as the main treatment modality. Adjuvant therapies, including radiation, chemotherapy, and/or hormonal therapy, have limited benefit on overall survival; however, this may be due to the lack of good randomized controlled trials of sufficient size because of uterine sarcomas' rare and aggressive nature. For patients with metastatic recurrent disease, aggressive therapy is limited by low response rates and limited duration of response. For patients with uterine sarcomas, enrollment in clinical trials is strongly encouraged.


Influence of different polymers on crystallization tendency and dissolution behavior of cilnidipine in solid dispersions.
Cilnidipine (CN) is a novel dihydropyridine calcium antagonist that is practically insoluble in aqueous media and exhibits a low oral bioavailability or limited clinical efficacy. This study investigated the effects of three commercial and chemically diverse polymers - PVP, PVP/VA and Soluplus - on crystallization tendency and in vitro dissolution profiles of CN in order to determine an optimum carrier for composing the preferred solid dispersion (SD) of CN. All these co-evaporated systems were characterized up to 3 months by thermoanalytical (DSC), crystallographic (POM, PXRD), microscopic (SEM) and spectroscopic (FTIR) techniques. The results showed that the polymers could be sorted by their effects of inhibiting CN crystallization in the ascending order: Soluplus, PVP/VA, PVP. The sequence was in accordance with that of the strength of drug-polymer hydrogen bonds revealed by FTIR spectra. It could be ascribed to relative hydrogen-bonding acceptor strengths of N-vinylpyrrolidone moiety in the polymer molecules. On the other hand, all the SDs showed enhanced dissolution profiles compared to pure CN alone. On their effects of enhancing CN dissolution, the polymers could be sorted in the descending order: Soluplus, PVP, PVP/VA. It implied that the dissolution behavior of CN could bear a close relationship to both hydration capacity and hydrogen-bonding interaction tendency of moieties of the polymers. It might suggest an optimal formulation for CN comprising both PVP and Soluplus.


Funding and Provision Models for Mobile Technology for Persons with Disabilities.
Research has yet to full investigate the multidimensional factors and mechanisms that contribute to access and adoption of Assistive Technology (AT). This mini-session aims to explore this gap by providing initial indicators for the social return on investment (SRoI) for including mainstream consumer technology in AT provision schemes and report on an analysis of key stakeholder perspectives and documents funded by the Global Accessibility Reporting Initiative (GARI).


The influence of dexamethasone on behaviorally conditioned immunomodulation and plasma corticosterone.
Utilizing a conditioned taste aversion paradigm we have previously shown that rats re-exposed to a saccharin solution previously paired with cyclophosphamide (CY) demonstrate significantly reduced in vitro mitogen-induced spleen cell proliferation and IgM secretion assessed 24 h after saccharin re-exposure. In this report treatment of similarly conditioned rats with dexamethasone (DEX) either before conditioning or before re-exposure abrogated the conditioned modulation of pokeweed mitogen (PWM)-induced spleen cell proliferation. The finding that DEX pretreatment on the conditioning day was as effective in abrogating the conditioned response as DEX treatment prior to the test day does not support pituitary-adrenal mediation of the conditioned immusuppressive effect following re-exposure of conditioned animals to the CS. There was no significant conditioned immunosuppression observed with respect to PHA- and Con A-induced proliferation and the influence of DEX on these parameters could not be assessed. The effect on PWM-induced IgM production was inconclusive since the reduced IgM response among conditioned animals was of only borderline significance.