Assessment of estrogenic and androgenic activity in PM10 air samples from an urban, industrial and rural area in Flanders (Belgium) using the CALUX bioassay.
Endocrine disrupting chemicals represent a broad class of compounds, are widespread in the environment and can pose severe health effects. The objective of this study was to investigate and compare the overall estrogen and androgen activating potential of PM10 air samples at an urban, rural and industrial location in Flanders, using a human in vitro cell bioassay. PM10 samples were collected on glass fiber filters every six days between April 2013 and January 2014 using a high-volume sampler. Extraction was executed with a hexane/acetone mixture before analysis using a recombinant estrogen- or androgen responsive human carcinoma cell line. Results were expressed as bioanalytical equivalents (BEQs) per cubic meter of air. High fluctuations in estrogenic activity were observed during the entire sampling period, with median BEQs of 32.1, 35.9 and 31.1 fg E2-Eq m(-)³ in the industrial, urban and rural background area, respectively. Estrogenic activity was measured in 70% of the samples, while no androgenic activity was observed in any of the samples. The estrogenic activity in the industrial area was positively correlated with the airborne concentration of the sum of the non-carcinogenic PAHs pyrene and fluoranthene (rho=0.48; p<0.01) and the sum of the carcinogenic PAHs (rho=0.36; p=0.05). This study showed that no androgenic activity was present in PM10 and that although the median estrogenic activity was rather low and comparable in the three locations, high fluctuations in estrogenic response exist over time. While atmospheric PAHs contributed to the observed estrogenic response, especially in the industrial area, the chemicals responsible for the majority of estrogenic activity remain to be identified.


Complement profile in childhood immune thrombocytopenic purpura: a prospective pilot study.
Immune thrombocytopenic purpura (ITP) is a frequent, usually acute hematologic complication of viral diseases in children. Its evolution is usually benign with spontaneous resolution. Some authors have raised the hypothesis of a possible role of the complement system in the pathogenesis of ITP. In the present study, we measured the complement system components in 25 children with ITP. The complement system was abnormal in most patients with ITP as compared with the control group: 20 of the 25 patients had at least one low-component level. The most affected components were properdin, factor H (p=0.005 and p=0.001, respectively), C1q, C9, and factor B. Our results may indicate a possible role for the complement system in the pathogenesis of pediatric ITP.


Coronary artery-left ventricular communications: a report of two cases and review of the literature.
Two patients with chest pain had angiographically-demonstrated communications between the three coronary arteries and the left ventricular chamber. Communications between coronary arteries and the left ventricle are unusual and communications between all three coronary arteries and the left ventricle are rare. These anomalies are, however, commonly associated with symptoms of chest pain. The presence of left ventricular hypertrophy and a widened pulse pressure may suggest a greater hemodynamic effect of the shunt flow than often suspected angiographically.


A quantitative structure-activity relationship study on some sulfolanes and arylthiomethanes acting as HIV-1 protease inhibitors.
A quantitative structure-activity relationship (QSAR) study on some sulfolanes and arylthiomethanes acting as human immunodeficiency virus-1 (HIV-1) protease inhibitors reveals that in the case of sulfolanes an octahydropyrindene ring and a five-membered 3(S)-sulfolane ring with a hydrophobic 2-substituent (cis to 3-substituent) will be crucial for the inhibition activity. The binding of a sulfolane, which is a nonpeptidic molecule, with the enzyme is shown to partly mimic the binding of a peptidic inhibitor. The 2-substituent is found to have strong hydrophobic interaction with the receptor. Similarly, in the case of arylthiomethanes, one of the substituents of the methane is found to have strong hydrophobic interaction with the enzyme, while the aryl substituent (4-hydroxy-6-phenyl-2-oxo-2H-pyran-3-yl) is assumed to be involved in the hydrogen bondings.


Unusual case of small cell gastric carcinoma: case report and literature review.
Small cell carcinomas are among the most aggressive, poorly differentiated, and highly malignant of the neuroendocrine tumors (NETs). Of which, small cell gastric carcinoma is a rare small cell neuroendocrine tumor. The purpose of our study was to present this case and perform a comprehensive literature review. We review a case of small cell gastric carcinoma that is particularly unusual in that it occurred in a woman from the US when the majority of cases of small cell gastric carcinoma have been reported in men from East Asia, and more specifically, from Japan. The diagnosis was made after endoscopy revealed a large ulcerated mass in the gastric cardia of Borrmann type 3. Biopsies revealed multiple small basophilic cells underlying the squamous epithelium of the esophagus and cardiac mucosa, indicating the presence of a tumor at the gastroesophageal junction. Immunostaining established the diagnosis with positive stains for chromogranin, synaptophysin, and CD56. Our patient is being treated with chemotherapy, but many different treatment regimens have been tried for small cell gastric carcinoma with variable success. Overall prognosis for small cell gastric carcinoma is dismal. Neuroendocrine tumors in general have variable clinical behaviors and prognosis is dependent on the neuroendocrine tumor type. The adoption of a standardized classification system for neuroendocrine tumors could improve the recognition of infrequently encountered neuroendocrine tumors like small cell gastric carcinoma and will enhance strategies for treatment and thus improve prognosis for patients with these rare and aggressive tumors.


m6A modification of circHPS5 and hepatocellular carcinoma progression through HMGA2 expression.
N6-methyladenosine (m6A) is capable of mediating circRNA generation in carcinoma biology. Nevertheless, the posttranscriptional systems of m6A and circRNA in hepatocellular carcinoma (HCC) development are still unclear. The present study identified a circRNA with m6A modification, circHPS5, which was increased in neoplasm HCC tissues and indicated poor patient survival. Silencing of circHPS5 inhibited epithelial-mesenchymal transition (EMT) and cancer stem-like cell (CSC) phenotypes. Notably, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. In addition, we demonstrated that circHPS5 can act as a miR-370 sponge to regulate the expression of HMGA2 and further accelerate HCC cell tumorigenesis. Accordingly, the m6A modification of circHPS5 was found to modulate cytoplasmic output and increase HMGA2 expression to facilitate HCC development. The new regulatory model of "circHPS5-HMGA2" provides a new perspective for circHPS5 as an important prognostic marker and therapeutic target in HCC and provides mechanistic insight for exploring the carcinogenic mechanism of circHPS5 in HCC.


The dexamethasone suppression test and plasma dexamethasone in generalized anxiety disorder.
A Dexamethasone Suppression Test nonsuppression rate of 27% was found in a group of 30 generalized anxiety disorder patients before treatment. The dexamethasone concentrations in the eight nonsuppressors were significantly lower than in eight suppressors matched by sex and age, but were similar to those in five nonsuppressors from a matched normal control group. The dexamethasone concentrations in the generalized anxiety disorder suppressors and a matched group of eight normal control suppressors were similar. After successful nondrug behavioral treatment, all generalized anxiety disorder patients were suppressors. Posttreatment dexamethasone concentrations in the initial nonsuppressor patients remained significantly lower than in the initial suppressors. The results suggest that low plasma dexamethasone concentrations after 1 mg oral dexamethasone may confer a vulnerability to nonsuppression that may be expressed in the presence of high state anxiety.


Mandibular bone changes in 24 years and skeletal fracture prediction.
The objectives of the investigation were to describe changes in mandibular bone structure with aging and to compare the usefulness of cortical and trabecular bone for fracture prediction. From 1968 to 1993, 1,003 women were examined. With the help of panoramic radiographs, cortex thickness was measured and cortex was categorized as: normal, moderately, or severely eroded. The trabeculation was assessed as sparse, mixed, or dense. Visually, the mandibular compact and trabecular bone transformed gradually during the 24 years. The compact bone became more porous, the intertrabecular spaces increased, and the radiographic image of the trabeculae seemed less mineralized. Cortex thickness increased up to the age of 50 and decreased significantly thereafter. At all examinations, the sparse trabeculation group had more fractures (71-78 %) than the non-sparse group (27-31 %), whereas the severely eroded compact group showed more fractures than the less eroded groups only in 1992/1993, 24 years later. Sparse trabecular pattern was associated with future fractures both in perimenopausal and older women (relative risk (RR), 1.47-4.37) and cortical erosion in older women (RR, 1.35-1.55). RR for future fracture associated with a severely eroded cortex increased to 4.98 for cohort 1930 in 1992/1993. RR for future fracture associated with sparse trabeculation increased to 11.43 for cohort 1922 in 1992/1993. Dental radiographs contain enough information to identify women most at risk of future fracture. When observing sparse mandibular trabeculation, dentists can identify 40-69 % of women at risk for future fractures, depending on participant age at examination.


Perioperative risk factors for acute kidney injury after liver resection surgery: an historical cohort study.
This study aimed to identify the incidence and risk factors for acute kidney injury (AKI) after liver resection surgery and to clarify the relationship between postoperative AKI and outcome. We conducted a historical cohort study of patients who underwent liver resection surgery with sevoflurane anesthesia from January 2004 to October 2011. Acute kidney injury was diagnosed based on the Acute Kidney Injury Network classification within 72 hr after the surgery. Patient data, surgical and anesthetic data, and laboratory data were extracted manually from the patients' electronic charts. Multivariable logistic regression analysis was used to identify perioperative risk factors for postoperative AKI. Acute kidney injury was diagnosed in 78 of 642 patients (12.1%; 95% confidence interval [CI]: 9.7 to 14.9). Multivariable analysis showed an independent association between postoperative AKI and preoperative estimated glomerular filtration rate (adjusted odds ratio [aOR] 0.74; 95% CI: 0.64 to 0.85), preoperative hypertension (aOR 2.10; 95% CI: 1.11 to 3.97), and intraoperative red blood cell transfusion (aOR 1.04; 95% CI: 1.01 to 1.07). Development of AKI within 72 hr after liver resection surgery was associated with increased hospital mortality, prolonged length of stay, and increased rates of mechanical ventilation, reintubation, and renal replacement therapy. Perioperative risk factors for AKI after liver resection surgery are similar to those established for other surgical procedures. Further studies are needed to establish causality and to determine whether interventions on modifiable risk factors can reduce the incidence of postoperative AKI and improve patient outcome. This study was registered at the University Hospital Medical Information Network (UMIN) Center (UMIN 000008089).


Nucleotide sequence of diatom plasmids: identification of open reading frames with similarity to site-specific recombinases.
We have determined the nucleotide sequence of two small circular DNA plasmids, pCf1 and pCf2 [22], from the marine diatom Cylindrotheca fusiformis. pCf1 is 4273 bp, and pCf2 is 4079 bp in size. In each plasmid, all of the major open reading frames (ORFs) are encoded on the same DNA strand. Two ORFs are similar, comparing the two plasmids. ORF218 (pCf1) and ORF217 (pCf2) share 80% amino acid identity and ORF482 (pCf1) and ORF484 (pCf2) share 54% amino acid identity. ORF218/217 shows significant similarity (28-31% amino acid identity) to the Tn3 class of resolvases. Resolvases are most commonly found in bacterial transposons. However, two other features found in the Tn3 class of transposon are missing in the plasmids; an ORF encoding a transposase and terminal inverted repeat sequences. This, and data mapping the portions of the plasmids that hybridize to genomic chloroplast DNA, suggest that the plasmids do not contain active transposons. By analogy with the R46 plasmid from Enterobacter [5, 6], another potential role for the resolvases encoded by pCf1 and pCf2 is the conversion of multimeric forms of the plasmid to monomers. The similarity of ORF218/217 to resolvases documents the first identification of a potential coding function in an algal plasmid.


Linking a one-dimensional pesticide fate model to a three-dimensional groundwater model to simulate pollution risks of shallow and deep groundwater underlying fractured till.
The one-dimensional pesticide fate model MACRO was loose-linked to the three-dimensional discrete fracture/matrix diffusion model FRAC3DVS to describe transport of the pesticide mecoprop in a fractured moraine till and local sand aquifer (5-5.5 m depth) overlying a regional limestone aquifer (16 m depth) at Havdrup, Denmark. Alternative approaches to describe the upper boundary in the groundwater model were examined. Field-scale simulations were run to compare a uniform upper boundary condition with a spatially variable upper boundary derived from Monte-Carlo simulations with MACRO. Plot-scale simulations were run to investigate the influence of the temporal resolution of the upper boundary conditions for fluxes in the groundwater model and the effects of different assumptions concerning the macropore/fracture connectivity between the two models. The influence of within-field variability of leaching on simulated mecoprop concentrations in the local aquifer was relatively small. A fully transient simulation with FRAC3DVS gave 20 times larger leaching to the regional aquifer compared to the case with steady-state water flow, assuming full connectivity with respect to macropores/fractures across the boundary between the two models. For fully transient simulations 'disconnecting' the macropores/fractures at the interface between the two models reduced leaching by a factor 24. A fully connected, transient simulation with FRAC3DVS, with spatially uniform upper boundary fluxes derived from a MACRO simulation with 'effective' parameters is therefore recommended for assessing leaching risks to the regional aquifer, at this, and similar sites.


Antibodies of the IgE and IgG isotype, serum IgE and circulating immune complexes in schistosomiasis intercalatum.
Individuals in an advanced phase of infection by Schistosoma intercalatum in whom viable ova are still present in the rectal mucosa but not excreted in detectable quantity, can be distinguished clinically from a younger group of individuals excreting S. intercalatum ova in their faeces. This clear-cut distinction is underlined by findings in parameters of humoral response. The ratio of anticercarial to anti-adult worm antibodies was higher in the group excreting eggs with probably more recent infection. Levels of total serum immunoglobulin were higher in this group, with the exception of serum IgA, which was lower as long as eggs were being excreted. In a later stage of the disease, relatively more IgG seems to be bound in circulating immune complexes. It is postulated that these stage specific patterns of humoral immune response represent the evolution of the host-parasite relationship during the infection.


Purification, properties, and evidence for two subtypes of human placenta hexokinase type I.
In human placenta 85% of total hexokinase activity (EC 220.127.116.11) was found in a soluble form. Of this, 70% is hexokinase type I while the remaining 30% is hexokinase type II. All the bound hexokinase is type I. Soluble hexokinase I was purified 11,000-fold by a combination of ion-exchange chromatography, affinity chromatography, and dye-ligand chromatography. The specific activity was 190 units/mg protein with a 75% yield. The enzyme shows only one band in nondenaturing polyacrylamide gel electrophoresis that stains for protein and enzymatic activity; however, two components (with Mr 112,000 and 103,000) were constantly seen in sodium dodecyl sulfate-gel electrophoresis. Many attempts were made to separate these two proteins under native conditions; however, only one peak of activity was obtained when the enzyme was submitted to gel filtration (Mr 118,000), preparative isoelectric focusing (pI 5.9), anion-exchange chromatography, hydroxylapatite chromatography, and affinity chromatography on immobilized dyes and immobilized glucosamine. The high and low molecular weight hexokinases show the same isoelectric point under denaturing conditions as determined by two-dimensional gel electrophoresis. Each hexokinase subtype was obtained by preparative sodium dodecyl sulfate electrophoresis followed by electroelution. Monospecific antibodies raised in rabbits against electroeluted high and low molecular weight hexokinases were not able to recognize the native enzymes but each of them detected both hexokinases on immunoblots. Amino acid compositions and peptide mapping by limited proteolysis of the high and low molecular weight hexokinases were also performed and suggested a strong homology between these two subtypes of human hexokinase I.


Erectile dysfunction and comorbid diseases, androgen deficiency, and diminished libido in men.
Erectile dysfunction affects an estimated one in ten men in the United States. According to one study, the prevalence of impotence at all degrees is approximately 52% in men aged 40 to 70 years. This prevalence rate might be underestimated, given patients' reluctance to discuss the issue with their physicians. Erectile dysfunction is often accompanied by comorbid conditions because of overlapping risk factors. It is important that physicians be aware of the frequency of this coexistence so that they may monitor all potential health concerns and treat patients optimally.


On Optimal and Quantum Code Construction from Cyclic Codes over FqPQ with Applications.
The key objective of this paper is to study the cyclic codes over mixed alphabets on the structure of FqPQ, where P=Fq[v]⟨v3-α22v⟩ and Q=Fq[u,v]⟨u2-α12,v3-α22v⟩ are nonchain finite rings and αi is in Fq/{0} for i∈{1,2}, where q=pm with m≥1 is a positive integer and p is an odd prime. Moreover, with the applications, we obtain better and new quantum error-correcting (QEC) codes. For another application over the ring P, we obtain several optimal codes with the help of the Gray image of cyclic codes.


Environmental enrichment mitigates the effects of basal forebrain lesions on cognitive flexibility.
The aim of the present study was to investigate whether basal forebrain lesions were able to impair a task requiring cognitive flexibility abilities and analyzing the effect of the rearing in an enriched environment on such form of flexibility in rats with or without basal forebrain cholinergic lesions. In adult rats reared in enriched or standard conditions of the cholinergic projection to the neocortex damage was inflicted by 192 IgG-saporin injection into Ch4 region of basal forebrain. Their performance was compared with those of intact animals reared in analogous conditions in a four-choice serial learning task which taps flexibility in adapting to changing response rules. The results underlined the crucial role of the basal forebrain in mediating cognitive flexibility behaviors and revealed that the increase in social interactions, cognitive stimulation and physical activity of the rearing in enriched environment attenuated impairments caused by the cholinergic lesion. These findings demonstrate that rearing in an enriched environment can improve the ability to cope with brain damage suffered in adulthood.


The antidepressant-like action of mGlu5 receptor antagonist, MTEP, in the tail suspension test in mice is serotonin dependent.
Numerous studies indicate the potential antidepressant actions of several mGlu5 receptor antagonists, including 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP). The explanation for the mechanism of these effects might be a key step in finding new antidepressant drugs (AD). The aim of the present study was to investigate the possible role of the serotonergic system in the antidepressant-like activity of MTEP in the tail suspension test (TST) in C57BL/6J mice, using selected antagonists of serotonergic receptors and by applying two different methods of serotonin (5-HT) depletion. The results of our studies showed that the mGlu5 receptor antagonist, MTEP, similar to the fluoxetine used as reference AD, did not induce antidepressant-like effects in mice pretreated with tryptophan hydroxylase inhibitor, parachlorophenylalanine. On the other hand, MTEP worked as a potential AD in the TST in mice fed on a tryptophan-free (TRP-free) diet for 3 weeks. However, fluoxetine, which was used as a reference control was also active in this experiment, suggesting that a TRP-free diet was not sufficiently effective in reducing the 5-HT level. Furthermore, we showed that the 5HT2A/2C antagonist, ritanserin, yet not the 5-HT1A antagonist, WAY100635, 5HT1B antagonist, SB224289 or 5HT4 antagonist, GR125487, reversed the antidepressant-like effects of MTEP in the TST. Finally, a sub-effective dose ofMTEP coadministered with a sub-effective dose of citalopram induced an antidepressant-like effect in the TST in mice. The results of our studies suggest the involvement of serotonergic system activation in the antidepressant-like effects of the mGlu5 antagonist, MTEP, in the TST in mice.


Pharmacological modulation of cold-induced pain in cutaneous leiomyomata.
In two patients with painful cutaneous leiomyomata, induction of pain by the application of an ice cube allowed assessment of a number of topical and systemic treatments aimed at reducing or preventing the pain. In one patient the alpha-adrenoceptor blocker, phenoxybenzamine alleviated cold-induced pain. In the second patient, topical 9% hyoscine hydrobromide (an anticholinergic agent) decreased pain induced by the ice cube, but was not helpful in reducing lesional pain due to cold weather.


Double orifice mitral valve in a patient with bicuspid aortic valve and coarctation of the aorta: A rare presentation.
Double orifice mitral valve is a rare condition and may be accompanied by a bicuspid aortic valve (sometimes normal functioning) and coarctation of the aorta. Echocardiography is valuable in detecting the accompanied anomalies. Management depends on the severity of mitral valve function and the severity of associated anomalies.


Multiple systems in decision making.
Neuroeconomics seeks to gain a greater understanding of decision making by combining theoretical and methodological principles from the fields of psychology, economics, and neuroscience. Initial studies using this multidisciplinary approach have found evidence suggesting that the brain may be employing multiple levels of processing when making decisions, and this notion is consistent with dual-processing theories that have received extensive theoretical consideration in the field of cognitive psychology, with these theories arguing for the dissociation between automatic and controlled components of processing. While behavioral studies provide compelling support for the distinction between automatic and controlled processing in judgment and decision making, less is known if these components have a corresponding neural substrate, with some researchers arguing that there is no evidence suggesting a distinct neural basis. This chapter will discuss the behavioral evidence supporting the dissociation between automatic and controlled processing in decision making and review recent literature suggesting potential neural systems that may underlie these processes.


Upper third molar internal structural organization and semicircular canal morphology in Plio-Pleistocene South African cercopithecoids.
Despite the abundance of cercopithecoids in the fossil record, especially in South Africa, and the recent development of morphometric approaches, uncertainties regarding the taxonomic identification of isolated cranio-dental specimens remain. Because cercopithecoids, nearly always found in stratigraphic association with hominin remains in Plio-Pleistocene deposits, are considered as sensitive ecological and chronological biomarkers, a significant effort should be made to clarify their palaeobiodiversity by assessing additional reliable morphological diagnostic criteria. Here we test the relevance of both molar crown internal structure and bony labyrinth morphology for discrimination of fossil cercopithecoid species. We use microtomographic-based 3D virtual imaging and quantitative analyses to investigate tooth endostructural organization and inner ear shape in 29 craniodental specimens from the South African sites of Kromdraai, Makapansgat, Sterkfontein and Swartkrans and provide the first detailed description of the internal structural condition characterizing this Plio-Pleistocene primate assemblage. Our preliminary results show that enamel-dentine junction morphology could be informative for discriminating highly autapomorphic taxa such as Theropithecus, while semicircular canal shape is tentatively proposed as an efficient criterion for diagnosing Dinopithecus ingens. Further research in virtual paleoprimatology may contribute to the identification of unassigned isolated fossil remains and shed new light on the internal craniodental morphology of extinct primate taxa.


Effect of zinc supplementation on growth performance, intestinal development, and intestinal barrier function in Pekin ducks with lipopolysaccharide challenge.
This study was conducted to investigate the influence of zinc (Zn) supplementation on growth performance, intestinal development and intestinal barrier function in Pekin ducks. A total of 480, one-day-old male Pekin ducks were divided into 6 groups with 8 replicates: 0 mg/kg Zn, 0 mg/kg Zn +0.5 mg/kg lipopolysaccharide (LPS), 30 mg/kg Zn, 30 mg/kg Zn +0.5 mg/kg LPS, 120 mg/kg Zn, 120 mg/kg Zn +0.5 mg/kg LPS. The duck primary intestinal epithelial cells (DIECs) were divided into 6 groups: D-Zn (Zinc deficiency, treated with 2 µmol/L zinc Chelator TPEN), A-Zn (Adequate Zinc, basal medium), H-Zn (High level of Zn, supplemented with 20 µmol/L Zn), D-Zn + 20 µg/mL LPS, A-Zn + 20 µg/mL LPS, H-Zn + 20 µg/mL LPS. The results were as follows: in vivo, with Zn supplementation of 120 mg/kg reduced LPS-induced decrease of growth performance and intestine damage (P < 0.05), and increased intestinal digestive enzyme activity of Pekin ducks (P < 0.05). In addition, Zn supplementation also attenuated LPS-induced intestinal epithelium permeability (P < 0.05), inhibited LPS-induced the expression of proinflammatory cytokines and apoptosis-related genes (P < 0.05), as well as reduced LPS-induced the intestinal stem cells mobilization of Pekin ducks (P < 0.05). In vitro, 20 µmol/L Zn inhibited LPS-induced expression of inflammatory factors and apoptosis-related genes (P < 0.05), promoted the expression of cytoprotection-related genes, and attenuated LPS-induced intestinal epithelium permeability in DIECs (P < 0.05). Mechanistically, 20 µmol/L Zn enhanced tight junction protein markers including CLDN-1, OCLD, and ZO-1 both at protein and mRNA levels (P < 0.05), and also increased the level of phosphorylation of TOR protein (P < 0.05) and activated the TOR signaling pathway. In conclusion, Zn improves growth performance, digestive enzyme activity, and intestinal barrier function of Pekin ducks. Importantly, Zn also reverses LPS-induced intestinal barrier damage via enhancing the expression of tight junction proteins and activating the TOR signaling pathway.


Neurosteroids: Can a 2alpha,3alpha-epoxy ring make up for the 3alpha-hydroxyl group?
Seven steroid epoxides were prepared from 5α-pregn-2-en-20-one and 5α-pregn-3-en-20-one and their side-chain derivatives. All compounds were tested in vitro for binding to γ-aminobutyric acid (GABAA) receptor, some of them also in vivo for anticonvulsant action. 2α,3α-Epoxy-5α-pregnan-20-one inhibited the TBPS binding to the GABAA receptor and showed a moderate anticonvulsant action in immature rats. In contrast, its 3α,4α-isomer was inactive. More polar epoxide derivatives, modified at the side chain were less active or inactive. Noteworthy, diol 20, the product of trans-diaxial opening of the 2α,3α-epoxide 4, was not able to inhibit the TBPS binding, showing that the activity of the epoxide is due to the compound itself and not to its hydrolytic product. The 3α-hydroxyl group is known to be essential for the GABAA receptor binding. Despite the shortness of in vivo effects which are probably due to metabolic inactivation of the products prepared, our results show that the 2α,3α-epoxy ring is another structural pattern with ability to bind the GABAAR.


Polarity switching and transient responses in single nanotube nanofluidic transistors.
We report the integration of inorganic nanotubes into metal-oxide-solution field effect transistors (FETs) which exhibit rapid field effect modulation of ionic conductance. Surface functionalization, analogous to doping in semiconductors, can switch the nanofluidic transistors from p-type to ambipolar and n-type field effect transistors. Transient study reveals the kinetics of field effect modulation is controlled by ion-exchange step. Nanofluidic FETs have potential implications in subfemtoliter analytical technology and large-scale nanofluidic integration.


Effects of corticosterone on neurones of the locus coeruleus, in the rat.
The effects of microelectrophoretic application of corticosterone (CS) on single neurones of the locus coeruleus (LC) were investigated in rats under urethane anaesthesia. Ejecting currents generally ranged from 10 to 60 nA. CS produced an excitatory effect in 73% of the neurones and no effect in 27%. The prevailingly excitatory effects induced by CS on LC neurones may be related to the regulation of those complex events, which constitute the 'stress response'.


Hybrid Theater and Uniportal Video-Assisted Thoracic Surgery: The Perfect Match for Lung Nodule Localization.
Cone-beam computed tomography provides unparalleled real-time imaging of the patient within the hybrid theater, which can be used for simultaneously diagnosing and localizing small pulmonary lesions for resection. Hybrid theater can guide more precise placement of electromagnetic navigation bronchoscopy tools, thereby increasing the diagnostic yield in biopsy procedures while reducing diffusion artifact in dye marking for nodule localization. Furthermore, hook-wires implantation that is widely used to assist in lesion localization for uniportal thoracoscopic surgery can take place in the hybrid suite, eliminating the common complications and discomfort associated with the conventional workflow carried out in the radiology suite.


Aryl hydrocarbon receptor nuclear translocator in human liver is regulated by miR-24.
Aryl hydrocarbon receptor nuclear translocator (ARNT) forms a heterodimer with aryl hydrocarbon receptor or hypoxia inducible factor 1α to mediate biological responses to xenobiotic exposure and hypoxia. Although the regulation mechanism of the ARNT expression is largely unknown, earlier studies reported that the human ARNT protein level was decreased by hydrogen peroxide or reactive oxygen species. These stimuli increase the miR-24 level in various human cell lines. In silico analysis predicts that some microRNAs including miR-16 and miR-23b may bind to ARNT mRNA. This background prompted us to investigate whether human ARNT is regulated by microRNAs. Overexpression of miR-24 into HuH-7 and HepG2 cells significantly decreased the ARNT protein level, but not the ARNT mRNA level, indicating translational repression. However, overexpression of miR-16 or miR-23b caused no change in the ARNT expression. The miR-24-dependent down-regulation of ARNT decreased the expression of its downstream genes such as CYP1A1 and carbonic anhydrase IX. Luciferase assay was performed to determine the element on the ARNT mRNA to which miR-24 binds. Finally, it was demonstrated that the miR-24 levels in a panel of 26 human livers were inversely correlated with the protein levels or the translational efficiency of ARNT. Taken together, we found that miR-24 negatively regulates ARNT expression in human liver, affecting the expression of its downstream genes. miR-24 would be one of the factors underlying the mechanisms by which ARNT protein is decreased by reactive oxygen species.


Aortic root diameter is associated with HLA-B27: identifying the patient with ankylosing spondylitis at risk for aortic valve regurgitation.
To assess the association between the aortic root diameter in HLA-B27 positive (+) and HLA-B27 negative (-) ankylosing spondylitis (AS) patients from the CARDAS cohort. The CARDAS study is a cross-sectional study in AS patients between 50 and 75 years who were recruited from a large rheumatology outpatient clinic. Patients underwent cardiovascular screening including echocardiography, with 2D, spectral, and color flow Doppler measurements. The aortic root was measured at sinuses of Valsalva during diastole. The aortic root diameter was adjusted for body surface area (BSA) (aortic root index, cm/m2). 193 Consecutive AS patients were included of whom 158 (82%) were HLA-B27 positive. The aortic root index was significantly higher in HLA-B27 + patients compared to HLA-B27- patients, respectively, 1.76 cm ± 0.21 vs. 1.64 cm ± 0.14, p < 0.001. No difference was seen in the prevalence of aortic valve regurgitation (AVR), p = 0.8. Regression analysis showed a significant association between HLA-B27 and aortic root index corrected for age, sex and cardiovascular risk factors (β 0.091, 95% CI 0.015-0.168, p = 0.02). Especially, male HLA-B27 + patients had a significantly increased aortic root index compared to male HLA-B27- AS patients, respectively, 1.76 cm (1.63-1.88) and 1.59 cm (1.53-1.68), p < 0.001. We found an increased aortic root index in elderly HLA-B27 + AS patients compared to HLA-B27- AS patients, especially in male patients. No difference was seen in the prevalence of AVR. However, as AVR can be progressive, echocardiographic monitoring in elderly male HLA-B27 + AS might be considered.


Technology-Delivered Interventions for Substance Use Among Adolescents.
Unhealthy alcohol and drug use are common among adolescents. A range of evidence-based interventions are available, but are rarely accessed by adolescents because of barriers such as cost, limited dissemination, lack of motivation to change, and logistical obstacles such as lack of transportation. Technology-delivered approaches may facilitate receipt of treatment in this vulnerable population. The limited number of controlled trials in this area present a mixed picture in terms of efficacy. Although sufficient to merit close attention and expanded research, the current literature points to a strong need for larger samples and greater use of rigorous and replicable methods.


High-energy gamma-ray astronomy.
Gamma-ray astronomy above 10 MeV is difficult from the experimental point of view, but promising data are beginning to appear, as this survey progress report shows.


Back beliefs among elderly seeking health care due to back pain; psychometric properties of the Norwegian version of the back beliefs questionnaire.
The Back Beliefs Questionnaire (BBQ) is a 14-item patient-reported questionnaire that measures attitudes and beliefs about the consequences of back pain. The BBQ has recently been translated into Norwegian, but its psychometric properties have not yet been tested. The aim of this study is to evaluate the reliability and construct validity of the BBQ when used on elderly patients with back pain. A prospective cohort study with a test-retest design among 116 elderly patients (> 55 years of age) seeking primary care for a new episode of back pain. Test-retest, standard error of measurement (SEM), minimal detectable change (MDC), internal consistency and construct validity by a priori hypotheses (Spearman's- and Pearson correlation coefficient) were tested. A total of 116 patients, mean age (SD) 67.7 (8.3), were included and 63 patients responded to the test-retest assessment. The mean (SD) BBQ sum scores (range 9-45) were 29.8 (7.0) and 29.2 (6.7) for the test and retest respectively. The test-retest was acceptable with an intraclass correlation coefficient of 0.71 (95% CI, 0.54-0.82), SEM was 3.8 and MDC 10.5. Internal consistency with Cronbach's alpha was good (0.82) and acceptable construct validity was supported by the confirmation of 75% of the a priori hypotheses. The Norwegian version of the BBQ demonstrated acceptable test-retest reliability and good construct validity and can be used to assess pessimistic beliefs in elderly patients with back pain.


[Use of a portable ultrasound system in the perisurgical assessment of head and neck patients].
The use of high resolution ultrasound is an established diagnostic method. A disadvantage of current high end systems is that transporting the device into the operating theatre or an intensive care unit requires time and logistic effort. We report results of an evaluation of a portable ultrasound system in the diagnosis and treatment of the head and neck area. Indications and value of a portable device in the clinical setting of an operation theatre and intensive care unit were assessed. Within a period of 5 months, 48 patients were included in this prospectively designed study using a portable ultrasound system with B-scan/color Doppler mode (SonoSite TITAN, Firma SonoSite® Germany) and an 7.5 MHz broadband linear array transducer. Two experienced physicians recorded the location and examination conditions, imaging mode, time expenditure, indication and diagnosis. The examiner also commented about whether the use of a portable laptop system considerably improved the therapy decision. The analysis included descriptive statistics for interpretation of the results. The most frequent use of the ultrasound system was the pre- or intrasurgical "pinpointing" of tumours in the soft tissues of the neck or in salivary glands. The average time for the examination was 6 min. In 79 % of the cases, the examiner stated a definite improvement of the therapy decision through the use of the portable ultrasound. We could demonstrate that a portable ultrasound system is a time-saving, economic and ubiquitously applicable method of imaging. Diagnosis and surgical planning are optimized. Thus, in larger hospitals and clinics, a portable ultrasound device is a logical complement to a stationary unit.


The central nervous system--immune system relationship.
Research investigating the pathogenesis of schizophrenia has demonstrated that cellular immune reactions, such as those that occur in known autoimmune diseases, may participate in producing alterations of the central nervous system. Furthermore, epidemiologic studies of immune-mediated diseases have suggested that activation of the central nervous system by stressful stimuli may be capable of influencing the function of the immune system. In support of that interaction, research using animal models of stress has provided valuable information as to the effect of stress on basic immune function and susceptibility to infectious disease. Possible hormonal and direct mechanisms of the central nervous system-immune system interaction have been proposed.


Edible bird's nest: food or medicine?
Edible bird's nest (EBN) is derived from the saliva of certain types of swiftlets. It is consumed in many parts of the world for its nutritional and medicinal values. Although many claims have been made on the therapeutic and health-promoting effects of EBN, scientific documentations regarding these effects are very limited in published literature. It is not until recently that the biological effects of EBN are being investigated and evidence-based studies are being conducted. Several studies have found that EBN may enhance cell proliferation and differentiation and various beneficial effects have been reported in vitro as well as in vivo. While these studies point towards the potential use of EBN in the treatment or even prevention of several diseases, the mechanisms of action of EBN remain largely unknown and more explorations are needed. This review is one of the very few scientific reviews on EBN which focuses on recent evidence-based discoveries.


Feasibility of a new free mobility procedure to evaluate the function of the autonomic nervous system in patients with syncope.
To propose a new test to evaluate the autonomic nervous system in patients with syncope: Multimodal Monitoring for Diagnosis of Dysautonomia (MMDD). We included 21 patients with syncope (16 female, 6 male, mean age 43.5 years) and 21 with no-syncope subjects (15 female, 7 male, mean age 45.1 years) to perform a test of nine 2-min stages: four while resting and four during active testing of autonomic response. Transcranial-Doppler, electrocardiogram, and photoplethysmography blood pressure pulse-to-pulse monitoring, allow registering six variables from the Middle Cerebral Artery and four from the Cardiovascular System. We analyze each variable's mean differences in each stage and its change when they pass from one stage to another with the T and Z tests. To understand the significance of the change, we use a logistic regression model for a certain subgroup of variables. Since we have a small dataset, we use the bootstrap technique to infer the general behavior that characterizes a syncope. Our data confirm differences between syncope and non-syncope patients during MMDD stress stages 2, 4, 6 and 8. Bootstrap and multivariate logistic regression allow us to identify which sets of variables in each of these stages of the MMDD are sufficiently sensitive to recognizing syncope. MMDD protocol can recognize a syncope patient with some confidence by detecting subtle changes in the autonomic nervous system. This protocol encourages us to continue to study the effectiveness of MMDD protocol allowing a new approach to future research.


Potentially inappropriate medication in acute hospitalized elderly patients with polypharmacy: an observational study comparing PRISCUS, STOPP, and Beers criteria.
To compare the prevalence of potentially inappropriate medication (PIM) in the elderly according to the PRISCUS list, STOPP criteria, and Beers criteria. Secondary, to describe the differences using the three criteria focused on the inappropriate prescription of psychotropic drugs in the elderly. A retrospective study was performed at Severo Ochoa University Hospital. The study included 365 patients, aged 80 years and older, living in Madrid, Spain. 93.42% of patients received at least one PIM during hospitalization. Using the PRISCUS list, this changed from 32.6 to 2.7% at discharge. Applying STOPP criteria lowered the percentage from 65.20 to 10.95%, and with Beers criteria from 80.27 to 10.13. Lower Barthel index at admission was associated with an increased relative risk for receiving at least one PIM (OR 1.79, 95% CI 1.15-2.80, p = 0.024) using PRISCUS list as a tool in conjunction with STOPP criteria (OR 1.44, 95% CI 0.89-2.33, p = 0.037). Polypharmacy at admission predicted the presence of PIMs with STOPP criteria (OR 1.74, 95% CI 1.07-2.84, p = 0.001). Regarding psychotropic medicines, 208 patients (56.98%) received at least one psychotropic medicine during hospitalization. A total of 26.30% of patients were treated with psychotropic medicines, detected by the PRISCUS list, and 53.97% and 29.85% with STOPP and Beers, respectively. Explicit criteria are a useful tool for identifying during hospitalization of the elderly patients. As indicated by the results, new research is needed to carry out an adaptation in our country that includes an evaluation of the strengths of the three tools to decrease PIMs and improve prescription in the elderly.


Efficacy and safety of tralokinumab in the treatment of atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.
To assess the efficacy and safety of Tralokinumab in the treatment of moderate-to-severe atopic dermatitis (AD). PubMed, Embase, Clinical Trials Website, and Cochrane Library were systematically searched for eligible randomized controlled trials which assessed the effects of Tralokinumab on AD. Primary outcomes included Scoring Atopic Dermatitis score, EASI-75%, and Investigator's Global Assessment score of 0 or 1 in 12 to 16 weeks. Secondary outcomes included the Eczema area and severity index score, the Numeric Rating Scales score, the dermatology life quality index score, and the overall incidence of adverse events. The quality of included studies was evaluated using the Cochrane System and the modified Jadad scale. Analysis was performed using Stata 16 software. Eight randomized controlled trials involving 2878 patients were included in this meta-analysis. Compared to placebo, Tralokinumab treatment exhibited a significantly higher Scoring Atopic Dermatitis score [SMD = -0.53, 95% confidence intervals [CI]: -0.62 to -0.44, P < .00001], an increased number of patients with EASI-75% [odds ratio (OR) = 2.44, 95% CI: 2.00-2.97, P < .00001] and Investigator's Global Assessment score of 0 or 1 in 12 to 16 weeks [OR = 2.12, 95% CI: 1.71-2.63, P < .00001]. No significant difference was observed in the incidence of overall adverse events [OR = 1.00, 95% CI: 0.85-1.18, P = 1.00] between the 2 groups. Tralokinumab is effective and safe in treatment of moderate-to-severe AD.


Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. falciparum.
Resistance of Plasmodium falciparum to chloroquine shares features with the multidrug resistance (MDR) phenotype of mammalian tumor cells. We report here the sequence of pfmdr, the P. falciparum homolog of mdr. We show that pfmdr is amplified in some chloroquine-resistant parasites but not in any of the sensitive isolates examined and that pfmdr transcript levels are increased. The gene is located on chromosome 5, and in one chloroquine-resistant line with an amplified pfmdr gene, chromosome 5 is greatly enlarged. The chromosome heterogeneity is due to varying copy numbers of different-sized pfmdr-containing amplicons. The existence of an mdr gene in P. falciparum and its amplification in some chloroquine-resistant lines greatly adds to the circumstantial evidence that pfmdr mediates chloroquine resistance in these lines.


Comparative pharmacokinetic analysis of six major bioactive constituents using UPLC-MS/MS in samples isolated from normal and diabetic nephropathy rats after oral administration of Gushen Jiedu capsule.
Berberine, palmatine, physcion, rhein, calycosin-7-O-glucoside, and ferulic acid are six major active consituents that are present in Gushen Jiedu capsule (GSJD) extracts. The aim of this study was to determine the pharmacokinetics of the six active consituents in vivo by a rapid, sensitive, and precise UPLC-MS/MS method, which were compared between normal and diabetic nephropathy (DN) rats. Good separation of the target analytes and internal standards (ketoprofen and puerarin) was obtained on a Waters BEH C18 UPLC column with a mobile phase of 0.1 % formic acid acetonitrile-0.1 % formic acid water. All the calibration curves showed good linearity with a regression coefficient (r2) of ≥ 0.9908. The lower limits of quantification (LLOQ) for berberine, palmatine, physcion, rhein, calycosin-7-O-glucoside, and ferulic acid were 20, 2.5, 20, 20, 2.5, and 2.5 ng/mL, respectively. The relative standard deviations (RSDs) of intra-day and inter-day precision were all within 12.66 %, and the relative errors of intra-day and inter-day accuracy ranged from - 15.00 to 14.93 %. Good extraction recovery and matrix effects were obtained. The stability study confirmed the stability of the six analytes (RSD < 15 %). Finally, the data showed that the pharmacokinetic parameters (especially CLz/F, AUC and Tmax) of the six target analytes in DN rats were significantly different from those in normal rats. PK studies under pathological conditions could provide new thoughts to elucidate the underlying mechanism of GSJD and promote the clinical development of GSJD to treat DN.


Serine proteases and cardiac function.
The serine proteases of the trypsin superfamily are versatile enzymes involved in a variety of biological processes. In the cardiovascular system, the importance of these enzymes in blood coagulation, platelet activation, fibrinolysis, and thrombosis has been well established. Recent studies have shown that trypin-like serine proteases are also important in maintaining cardiac function and contribute to heart-related disease processes. In this review, we describe the biological function of corin, tissue kallikrein, chymase and urokinase and discuss their roles in cardiovascular diseases such as hypertension, cardiac hypertrophy, heart failure, and aneurysm.


Contribution of MicroRNAs to autoimmune diseases.
MicroRNAs are a class of evolutionarily conserved, short non-coding RNAs that post-transcriptionally modulate the expression of multiple target genes. They are implicated in almost every biological process, including pathways involved in immune homeostasis, such as immune cell development, central and peripheral tolerance, and T helper cell differentiation. Alterations in miRNA expression and function can lead to major dysfunction of the immune system and mediate susceptibility to autoimmune disease. Here, we discuss the role of miRNAs in the maintenance of immune tolerance to self-antigens and the gain or loss of miRNA functions on tissue inflammation and autoimmunity.


AAV-mediated PEX1 gene augmentation improves visual function in the PEX1-Gly844Asp mouse model for mild Zellweger spectrum disorder.
Patients with Zellweger spectrum disorder (ZSD) commonly present with vision loss due to mutations in PEX genes required for peroxisome assembly and function. Here, we evaluate PEX1 retinal gene augmentation therapy in a mouse model of mild ZSD bearing the murine equivalent (PEX1-p[Gly844Asp]) of the most common human mutation. Experimental adeno-associated virus 8.cytomegalovirus.human PEX1.hemagglutinin (AAV8.CMV.HsPEX1.HA) and control AAV8.CMV.EGFP vectors were administered by subretinal injection in contralateral eyes of early (5-week-old)- or later (9-week-old)-stage retinopathy cohorts. HsPEX1.HA protein was expressed in the retina with no gross histologic side effects. Peroxisomal metabolic functions, assessed by retinal C26:0 lysophosphatidylcholine (lyso-PC) levels, were partially normalized after therapeutic vector treatment. Full-field flash electroretinogram (ffERG) analyses at 8 weeks post-injection showed a 2-fold improved retinal response in the therapeutic relative to control vector-injected eyes. ffERG improved by 1.6- to 2.5-fold in the therapeutic vector-injected eyes when each cohort reached 25 weeks of age. At 32 weeks of age, the average ffERG response was double in the therapeutic relative to control vector-injected eyes in both cohorts. Optomotor reflex analyses trended toward improvement. These proof-of-concept studies represent the first application of gene augmentation therapy to treat peroxisome biogenesis disorders and support the potential for retinal gene delivery to improve vision in these patients.


Symposium: Imaging modalities for drug-related osteonecrosis of the jaw (4), CT and MR imaging findings of antiresorptive agent-related osteonecrosis of the jaws/medication-related osteonecrosis of the jaw (secondary publication).
Generally, CT and MR images of antiresorptive agent-related osteonecrosis of the jaw (ARONJ)/medication-related osteonecrosis of the jaw (MRONJ) show nonspecific findings as seen in active osteomyelitis.However, there are some characteristics as follows; unilateral maxillary sinusitis adjacent to ipsilateral maxillary ARONJ/MRONJ, DRONJ presenting larger sequestrum and periosteal reaction more frequently than BRONJ, BRONJ resulting from intravenous administration of the drug presenting larger and more frequent buccolingual cortical bone perforations than BRONJ from oral administration, and better diagnostic accuracy of extent of perilesional soft tissue inflammation on MR imaging than CT. The CT and MR imaging features of ARONJ/MRONJ are summarized in this report.


Highly improved aqueous lubrication of polymer surface by noncovalently bonding hyaluronic acid-based hydration layer for endotracheal intubation.
Hydration lubrication is the key responsible for the exceptionally low boundary friction between biosurfaces. However, it is a challenge to settle a hydration layer on a polymer surface via a noncovalent manner. Herein, we develop a highly lubricated coating absorbed onto the polymer surface via intermolecular association of hyaluronic acid (HA)-based micelles. A poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer (Pluronic, F127) is recruited to complex with HA and further self-assembled to form a thick micelle layer. High water-retaining capacity of the HA/F127 coating enables the decorated surface with excellent hydrophilicity and boundary lubrication, where the coefficient of friction in aqueous media is reduced by 60% compared with the bare polymer surface. The HA/F127 coating suppresses nonspecific protein adsorption and exhibits good biocompatibility. More remarkably, an in vivo cynomolgus monkey model, demonstrates the utility of the HA/F127 coating in alleviating or preventing complications of endotracheal intubation, such as foreign irritation, airway mucosal damage, and inflammatory response. This cost-effective and scalable approach is suitable to manufacture interventional devices especially disposable medical devices with highly lubricated surface.


Octanoic acid promotes clearance of antibiotic-tolerant cells and eradicates biofilms of Staphylococcus aureus isolated from recurrent bovine mastitis.
Antibiotic therapy is the primary treatment for bovine mastitis, but the drawbacks of this strategy include poor cure rate and economic losses from the need to discard milk with antibiotic residues. Unfortunately, few other treatment options are currently available for mastitis. Failure of antibiotic treatments is often attributed to formation of bacterial biofilms and abscesses in the mammary gland tissue, which lead to chronic infections that are difficult to eradicate and drive recurrent disease. A major mastitis-causing pathogen (MCP) associated with biofilms in bovine mastitis is Staphylococcus aureus. In this study, we demonstrate that octanoic acid has broad-spectrum microbicidal activity against MCPs and effectively inhibits S. aureus biofilm formation in milk (>50% inhibition at 3.13 mM). Octanoic acid effectively clears biofilms (95% eradication at 1X minimum bactericidal concentration, MBC) and infrequently induces S. aureus small colony variants (SCVs) that may cause recurrent mastitis. Additionally, octanoic acid rapidly kills persistent biofilm cells and cells with antibiotic tolerance (within 4 h). In contrast, antibiotics treated at >100X MBC cannot eradicate biofilms but do induce SCVs and antibiotic-tolerant cells. These effects may accelerate the transition from biofilm to chronic infection. Thus, octanoic acid exhibits bactericidal action against S. aureus biofilms, and it is less likely than antibiotic therapy to induce persistent cells and pathogen tolerance. Moreover, octanoic acid acts additively with antibiotics against S. aureus, and it attenuates tetracycline-induced virulence factor gene expression in S. aureus cells. According to these data, octanoic acid may prevent the pathological progression of bovine mastitis and offer a new strategy for treating the condition.


Effects of Mn2+ and humic acid on microbial community structures, functional genes for nitrogen and phosphorus removal, and heavy metal resistance genes in wastewater treatment.
Considering the wide occurrence of Mn2+ and humic acid (HA) in environmental media, the effects of Mn2+ (5-16 mg/L) and HA (10 mg/L) on microbial community structures, functional genes for nitrogen and phosphorus removal, and heavy metal resistance genes (HMRGs) were investigated in wastewater treatment using sequencing batch bioreactors (SBRs). The treatment efficiencies of influent chemical oxygen demands (COD), NH4+-N, and PO43--P were unaffected during the entire operational processes irrespective of whether Mn2+ and HA were supplied. Although the functional prediction of genetic information via sequencing analysis showed that the microbial activity was not influenced by Mn2+ and HA from different SBRs, the abundance of dominant phyla (Proteobacteria, Actinobacteriota, Firmicutes, and Bacteroidota), classes (Saccharimonadia, Gammaproteobacteria, and Bacilli), and genera (unidentified_Chloroplast, TM7a, Micropruina, Candidatus_Competibacter, Lactobacillus, OLB12, and Pediococcus) was different. Compared to the SBR without Mn2+ and HA supplementation, the abundance of functional genes for nitrogen and phosphorus removal (narG, nirS, nosZ, ppk, and phoD) and HMRGs (corA and mntA) significantly increased under Mn2+ stress, but significantly decreased with the addition of HA except for genes nirS and ppk. The abundance of genes corA and mntA was related to the partially dominant microbes and functional genes, and might be reduced by supplying HA. This study provides insight into the effects of Mn2+ and HA on functional genes for nitrogen and phosphorus removal and HMRGs in wastewater treatment.


Redesign of hydrophobic quantum dots mitigates ligand-dependent toxicity in the nematode C. elegans.
Surface properties of engineered nanomaterials (ENMs) have been shown to influence their interaction with biological systems. However, studies to date have largely focused on hydrophilic materials, likely due to biocompatibility concerns and aqueous exposure conditions necessary for many model systems. Therefore, a knowledge gap exists in nanotoxicity literature for impacts of hydrophobic ENMs, with studies of hydrophobic materials largely limited to carbon ENMs. Here we demonstrate testing of hydrophobic quantum dots (QDs) using the nematode C. elegans, a model soil organism cultured on solid media and amenable to hydrophobic exposures. To evaluate the influence of hydrophobicity, we compared CdSe/ZnS QDs functionalized with hydrophobic trioctylphosphine oxide (TOPO) to identical QDs functionalized with hydrophilic dihydrolipoic acid-polyethylene glycol (DHLA-PEG) and alternative hydrophobic CdSe/ZnS QDs functionalized with oleic acid (OA). Results show that hydrophobic TOPO QDs are significantly more toxic than hydrophilic DHLA-PEG QDs, and substitution of TOPO with OA yields relatively non-toxic hydrophobic QDs. Fluorescence microscopy shows TOPO QDs loosely associated with the organism's cuticle, but atomic force microscopy shows no difference in cuticle structure from exposure. Importantly, TOPO ligand alone is as toxic as TOPO QDs, and our data suggests that TOPO may impact neuromuscular function, perhaps upon displacement from the QD surface. This study demonstrates the importance of examining ligand-specific impacts of hydrophobic ENMs and indicates OA-functionalized QDs as a potential alternative to TOPO QDs for reduced toxicity.


Do nitroxides protect cardiomyocytes from hydrogen peroxide or superoxide?
The aim of the research was to study the role played by extracellular O2-radicals, which are implicated in cardiac cell damage and the protective effect by cell-permeable, nitroxide, superoxide dismutase-mimics. Cardiomyocytes cultures from 1-day-old rats served as the test-system. Experiments were performed since 5th day in culture when > 80% of the cells were beating myocardial cells. Oxidative damage was induced by 0.5 mM hypoxanthine and 0.06 U/ml xanthine oxidase or by 10 mM glucose and 0.15 U/ml glucose oxidase. The parameters used to evaluate damages were spontaneous beating, lactate dehydrogenase release and ATP level. The rhythmic pulsation was followed microscopically. To determine the kinetics of cytosolic enzyme release from the cells, media samples were collected at various points of time and assayed for enzyme activity. To determine the cellular ATP, cells were washed with sodium phosphate buffer, scraped off and boiled for 3 min with sodium phosphate buffer. Following centrifugation the supernatant was collected and ATP was determined by the chemiluminogenic assay using firefly tails. The present results indicate that nitroxide stable free radicals in the millimolar concentration range, provide full protection without toxic side-effect. Unlike exogenously added SOD that failed to protect, exogenous catalase provided almost full protection. In addition, the metal-chelating agent dipyridyl, but not diethylene-triamine-pentaacetate or desferrioxamine, protected the cultured cells. The present results suggest that H2O2 is the predominant toxic species mediating the oxidative damage whereas extracellular superoxide radical does not contribute to cultured cardiomyocyte damage.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of the entire nucleotide and deduced amino acid sequences of the attenuated hog cholera vaccine strain GPE- and the wild-type parental strain ALD.
We have determined the complete nucleotide sequences of a live attenuated hog cholera virus (HCV) and its progenitor strain. The viral RNA of each strain consisted of 12,298 nucleotides including untranslated regions of 373 and 228 bases at the 5' and 3' end, respectively. There was a single large open reading frame spanning 11,697 nucleotides which could encode a large protein of 3,899 amino acids with a calculated molecular weight of 438-kDa. We have found 225 nucleotide difference between the two strains, of which six were located in the untranslated region. Four-sixths of these differences resulted in amino acid substitutions.


Pathway for degradation of 2-chloro-4-nitrophenol in Arthrobacter sp. SJCon.
Degradation of 2-Chloro-4-nitrophenol (2C4NP) was studied by Arthrobacter sp. SJCon, isolated from the soil of a pesticide contaminated site. This strain utilized 2C4NP as sole source of carbon and energy and degraded 2C4NP with stoichiometric release of nitrite and chloride ions. A metabolite was detected during the study of 2C4NP degradation and identified as chlorohydroquinone (CHQ) by thin layer chromatography (TLC), high performance liquid chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS). Inhibition study using 2,2'-dipyridyl showed that CHQ is a terminal aromatic compound in degradation pathway of 2C4NP. CHQ dioxygenase activity was observed in the crude extract of 2C4NP induced cells of the strain SJCon that suggested the cleavage of the CHQ to maleylacetate (MA). Our study clearly showed that Arthrobacter sp. SJCon degraded 2C4NP via formation of CHQ that further cleaved to MA by CHQ dioxygenase. This mechanism of degradation of 2C4NP differs from previously reported degradation pathways of 2C4NP.


Identification of autoantibodies to glial fibrillary acidic protein in spinal cord injury patients.
Traumatic spinal cord injury (SCI) is a devastating injury causing significant morbidity and mortality. Experimental studies have demonstrated that SCI induced cellular damage and disruption of the blood-spinal cord barrier can initiate an autoimmune response. This response is thought to be pathogenic and contribute to poor outcome. The objective of this research was to investigate whether human SCI mounts an autoimmune response to self-antigens. Plasma samples were collected longitudinally from SCI patients (n=18) at acute (T1, <48 h) and subacute (T2, 2-4 weeks) time points to probe western blots of human brain homogenates in order to screen patients for the presence of putative autoantibodies. To identify the corresponding antigens, two-dimensional gel electrophoresis, western blot and liquid chromatography coupled with mass spectrometry (LC-MS/MS) analyses were performed. We found that four of 18 patients (22%) had novel immunoreactive bands ranging in size from 36 to 42 kDa present in subacute, but not in acute, plasma samples suggesting postinjury production. To identify the cross-reacting antigens, we separated brain proteins by two-dimensional gel electrophoresis and identified nine immunoreactive spots. Amino acid sequence analysis of these spots identified peptides that mapped to glial fibrillary acidic protein. Our results suggest that ∼ 22% of SCI patients generated autoantibodies to glial fibrillary acidic protein. Future studies will be required to determine whether these autoantibodies contribute to the pathogenic sequelae of SCI.


Towards 4-dimensional atomic force spectroscopy using the spectral inversion method.
We introduce a novel and potentially powerful, yet relatively simple extension of the spectral inversion method, which offers the possibility of carrying out 4-dimensional (4D) atomic force spectroscopy. With the extended spectral inversion method it is theoretically possible to measure the tip-sample forces as a function of the three Cartesian coordinates in the scanning volume (x, y and z) and the vertical velocity of the tip, through a single 2-dimensional (2D) surface scan. Although signal-to-noise ratio limitations can currently prevent the accurate experimental implementation of the 4D method, and the extraction of rate-dependent material properties from the force maps is a formidable challenge, the spectral inversion method is a promising approach due to its dynamic nature, robustness, relative simplicity and previous successes.


[The structure of the round window membrane studied by thin section.- freeze-fracture- and scanning electron microscopic technique (author's transl)].
In thin sections of the round window membrane of chinchilla there were found tight junctions between the cells of the outer and of the inner cell layer as well. Their structure was demonstrated in freeze-fracture replica, and in the scanning electron microscope both faces of the membrane appeared uninterrupted. The tight junctions between the mucosal cells constantly became visible and are considered impermeable; however, the junctions connecting the mesothelial cells, which face the perilymph, demonstrated high susceptibility against differences in preparation and were structurally different.


The endothelin receptor antagonist, BQ-123, inhibits angiotensin II-induced contractions in rabbit aorta.
The purpose of this study was to examine the specificity of the cyclic pentapeptide ET(A) receptor antagonist BQ-123. BQ-123 competitively antagonized endothelin-1-induced contractions in rabbit aorta, increases in inositol phosphates in cultured rat vascular smooth muscle A10 cells, and binding of [125I]endothelin-1 to the cloned ETA receptor cDNA expressed in Cos 7 cells. In contrast, BQ-123 was a weak antagonist of [125I]endothelin-3 binding to rat cerebellar membranes and to membranes from Cos 7 cells transfected with the cloned ETB receptor cDNA. BQ-123 shifted concentration-response curves in isolated rabbit aorta elicited by angiotensin II, but did not bind to angiotensin II receptors nor affect angiotensin II-induced increases in inositol phosphates. BQ-123 also did not affect contractions induced by KCl or norepinephrine. These data suggest that endothelin may play a role in angiotensin II-induced contractions of rabbit aorta.


A reflex behavior mediated by monosynaptic connections between hair afferents and motoneurons in the larval tobacco hornworm, Manduca sexta.
In the tobacco hornworm caterpillar, tactile stimulation of sensory hairs located on the tip of a proleg (the planta) evokes ipsilateral or bilateral retraction of the prolegs in that segment. We have used electrophysiological and anatomical methods to investigate the excitatory neural pathways linking the planta hair afferents and the proleg retractor motoneurons (MNs). An important technical innovation was the development of an isolated proleg and desheathed ganglion preparation that permits rapid and reversible ionic manipulations and drug applications. Action potentials (spikes) in individual planta hair afferents produce time-locked excitatory postsynaptic potentials (EPSPs) in ipsilateral proleg MNs which appear to be chemically-mediated and monosynaptic: the EPSPs have a short and constant latency, they follow afferent spikes without failure, they are reversibly abolished in elevated Mg++ saline, and they persist in saline with elevated Mg++ and Ca++ levels. Planta hair afferents also excite ipsilateral MNs by polysynaptic pathways, and their excitation of contralateral proleg MNs is exclusively polysynaptic. Cobalt-staining of the proleg MNs and planta hair afferents shows that the afferents terminate in ventral neuropil, and the proleg MNs have an unusual ventral projection into this region. The ventral projection is on the ipsilateral side, which is consistent with the electrophysiological finding that time-locked EPSPs are found only from ipsilateral hairs. Two factors that contribute to the strong monosynaptic excitation of proleg MNs by ipsilateral planta hairs are the convergence of many hair afferents onto each MN, and the facilitation shown at each afferent-MN synapse. At least 6 afferents converge on each MN, and at short interspike intervals the afferent-evoked EPSPs are enhanced by as much as 400% by homosynaptic facilitation. The EPSP is abolished reversibly by the cholinergic antagonists curare and atropine, suggesting that the neurotransmitter at the synapse is acetylcholine (ACh). This is of particular interest because the ACh receptors of tobacco-feeding Manduca larvae are reported to be less nicotine-sensitive than those of other insects.


Pilot study evaluating the role of cardiac magnetic resonance imaging in monitoring adjuvant trastuzumab therapy for breast cancer.
To explore the incidence of subclinical cardiotoxicity in women treated with adjuvant trastuzumab in the early breast cancer setting using cardiac magnetic resonance imaging (cMRI). The cardiac function and myocardial tissue characteristics of 25 women who had completed adjuvant trastuzumab therapy greater than 6 months previously was evaluated using MRI and comparing this with symptoms and routine echocardiography. Evidence of myocardial tissue damage was seen in two women in the absence of functional change or previous cardiac symptoms. Tissue characterization using cMRI may provide a useful tool in defining trastuzumab induced cardiotoxicity.


MicroRNA-155 Inhibits Polarization of Macrophages to M2-Type and Suppresses Choroidal Neovascularization.
Arg-1+Ym-1+ M2-type macrophages play essential roles in the development of choroidal neovascularization (CNV). Thus, inhibition of M2-type macrophages may be effective in suppressing CNV. However, the potential mechanisms of macrophage polarization during development of CNV remain unclear. In this study, we report that microRNA-155 (miR-155) inhibited M2 polarization by targeting C/EBPβ in CNV model mice and in bone marrow-derived primary macrophages. Moreover, our data show that intravitreous injection of miR-155 mimics suppressed subretinal leakage and neovascularization. Therefore, we conclude that C/EBPβ plays a significant role in M2 macrophage polarization in CNV model, while miR-155 mimics could suppress CNV by inhibiting C/EBPβ activity and M2 macrophage polarization.


Sex-typical behavior in children born preterm at very low birth weight.
Perinatal events may alter psychosexual development. We aimed to assess whether a preterm birth at very low birth weight (VLBW; <1500 g) or antenatal synthetic glucocorticoids (sGC) given to the mother are associated with altered sex-typical behavior in childhood. Sex-typical behavior was assessed using the Pre-school Activities Inventory (PSAI) at the mean age of 4.9 years (SD 1.6) in 879 children, of whom 143 were preterm with VLBW (PT <1500 g, all exposed to sGC), 282 were preterm with birth weight ≥1500 g (PT ≥1500 g, 171 exposed to sGC), and 454 were full term (FT, 166 exposed to sGC). Antenatal sGC was not associated with PSAI scores in either sex. PT <1500 g boys had less male-typical PSAI scores than other boys, even in multivariate model adjusting for age, maternal age, antenatal sGC, number of brothers and sisters, and motor or cognitive impairment. PT <1500 g girls had less female-typical PSAI scores than other girls in the multivariate model. The effect size was small (d = 0.03) for both sexes. Preterm birth with VLBW is associated with reduced sex-typical behavior in childhood, which is in line with the previous data indicating altered psychosexual development in adults born preterm. Mechanisms underlying these observations are not fully understood. Preterm birth is associated with reduced rates of marriage and reproduction in adulthood, but sex-typical behavior in children born preterm has not been studied before. The results of this study indicate that preterm birth with very low birth weight <1500 g is associated with reduced sex-typical behavior in childhood in both sexes. These observations are in line with the previous data indicating altered psychosexual development in adults born preterm. Mechanisms underlying these observations are not fully understood and require further studies.


Trends in utilization, reimbursement, and price for DOACs and warfarin in the US Medicaid population from 2000 to 2020.
The use of direct oral anticoagulants (DOACs) is widely increasing in the United States (US). Warfarin has been the conventional anticoagulant used in the past few decades, but it has been gradually replaced by DOACs. The objective of the study was to analyze trends in utilization, reimbursement, and price for those anticoagulants in the US Medicaid population. Retrospective data analysis was conducted using the National Summary Files for the Medicaid State Drug Utilization Data. Study drugs included dabigatran, rivaroxaban, apixaban, edoxaban and warfarin. The study assessed secular trends of utilization, reimbursement, and per-prescription price. The data was collected from the first quarter of 2000 through to the second quarter of 2020 restricted for outpatient prescriptions only. During the 21-year study period, a substantial rise in total expenditures on warfarin and DOACs was observed from $144 million in 2000 to $694 million in 2020. Moreover, the utilization of DOACs has increased significantly since the first approval of Xarelto in 2010 from 1079 in 2011 to 1.5 million in 2019. The per-prescription price of DOACs increased from an average of $200 in 2011 to $407 in 2020. Conversely, the total number of prescriptions of Warfarin and branded Coumadin decreased from 2.4 million to 1.4 million and from 3.9 million to less than a million, respectively. The present study demonstrated a change in the trends of US expenditure and utilization for warfarin and DOACs with DOACs representing the majority of market share of both spending per prescription and reimbursement.


What urologists need to know about female-to-male genital confirmation surgery (phalloplasty and metoidioplasty): techniques, complications, and how to deal with them.
Transmasculine gender-affirming surgery (GAS) is technically challenging, and in the past associated with a high but improving complication rate. Few surgical centers are performing this surgery, which can include metoidioplasty and phalloplasty, and patients often travel great distances for their surgery. While many will continue care with their original surgeons, others cannot due to social/geographic factors, or because emergencies arise. Thus, patients may seek care with their local urologist for relief of delayed complications, the most common of which include urethral stricture, penile prosthesis issues and urethrocutaneous fistula. This review will discuss the surgical elements behind metoidioplasty and phalloplasty, and the diagnosis and treatment for the most common postoperative issues.


Not "either-or" but "which-when": A review of the evidence for integration in sensory preconditioning.
Sensory preconditioning protocols can be used to assess how the brain integrates memories that share common features. In these protocols, animals are first exposed to pairings of two relatively innocuous stimuli, S2 and S1 (stage 1), and then to pairings of one of these stimuli, S1, with an event of motivational significance (stage 2). Following this training, test presentations of S2 elicit responses appropriate to the motivationally significant event, and these responses are taken to indicate formation of distinct S2-S1 and S1-event memories that are integrated in some way to generate that responding. This paper reviews studies of sensory preconditioning in rats, mice, rabbits and people to determine whether S2-S1 and S1-event memories are integrated through a chaining process at the time of their retrieval (i.e., test presentations of S2 trigger retrieval of S1, and thereby, responses appropriate to the event); or "online" at the time of memory formation (i.e., in stage 2, S1 activates a representation of S2 such that both stimuli associate with the motivationally significant event). It finds that the type of integration is determined by the manner in which stimuli are presented in preconditioning as well as their familiarity. When the stimuli in preconditioning are presented repeatedly and/or serially (i.e., one after the other), the S2-S1 and S1-event memories are chained at the time of retrieval/testing. In contrast, when the stimuli in preconditioning are relatively novel and/or presented simultaneously, the S2-S1 and S1-event memories are integrated online. These statements are related to prior claims regarding the circumstances that promote different types of memory integration and, more generally, mechanisms of information processing in the mammalian brain.


Combined contrast-enhanced magnetic resonance and diffusion-weighted imaging reading adapted to the "Breast Imaging Reporting and Data System" for multiparametric 3-T imaging of breast lesions.
To develop and assess a combined reading for contrast-enhanced magnetic resonance (CE-MRI) and diffusion weighted imaging (DWI) adapted to the BI-RADS for multiparametric MRI of the breast at 3 T. A total of 247 patients with histopathologically verified breast lesions were included in this IRB-approved prospective study. All patients underwent CE-MR and DWI at 3 T. MRIs were classified according to BI-RADS and assessed for apparent diffusion coefficient (ADC) values. A reading method that adapted ADC thresholds to the assigned BI-RADS classification was developed. Sensitivity, specificity, diagnostic accuracy and the area under the curve were calculated. BI-RADS-adapted reading was compared with previously published reading methods in the same population. Inter- and intra-reader variability was assessed. Sensitivity of BI-RADS-adapted reading was not different from the high sensitivity of CE-MRI (P = 0.4). BI-RADS-adapted reading maximised specificity (89.4 %), which was significantly higher compared with CE-MRI (P < 0.001). Previous reading methods did not perform as well as the BI-RADS method except for a logistic regression model. BI-RADS-adapted reading was more sensitive in non-mass-like enhancements (NMLE) and was more robust to inter- and intra-reader variability. Multiparametric 3-T MRI of the breast using a BI-RADS-adapted reading is fast, simple to use and significantly improves the diagnostic accuracy of breast MRI. KEYPOINTS : • Multiparametric breast 3-T MRI with BI-RADS-adapted reading improves diagnostic accuracy. • BI-RADS-adapted reading of CE-MRI and DWI is based on established reporting guidelines. • BI-RADS-adapted reading is fast and easy to use in routine clinical practice. • BI-RADS-adapted reading is robust to intra- and inter-reader variability.


Epilepsy prevalence in Al-Manial Island, Egypt. A door-to-door survey.
Epidemiologic studies of epilepsy are lacking from the majority of the Arab countries; although there are significant needs for such studies. This study was conducted on a sample of Al-Manial Island, Cairo city, one of the highest cities in population density in the world. A community-based, door to door, cross-sectional study using multistage random sample including 512 families (1751 individuals). The study extended from March 2009 to September 2012 and involved three main stages; the preparatory stage, the field work stage and the stage of establishing epilepsy diagnosis and classifying confirmed epileptic patients. The lifetime point prevalence of epilepsy among inhabitants of Al-Manial island was 6.9/1000 inhabitants while the prevalence of active epilepsy was 5.1/1000 inhabitants. The age distribution showed bimodal peaks in adolescents and in elderly with equal sex ratio (6/855 vs 6/896). Focal seizures were the commonest type (58.3%) and the treatment gap was 66.7%. The prevalence of epilepsy among inhabitants of Al-Manial Island go in agreement with most global studies. High treatment gap detected in our study indicates that proper management of epilepsy requires a multi-factorial approach.


Contribution of polyamines metabolism and GABA shunt to chilling tolerance induced by nitric oxide in cold-stored banana fruit.
Effect of exogenous nitric oxide (NO) on polyamines (PAs) catabolism, γ-aminobutyric acid (GABA) shunt, proline accumulation and chilling injury of banana fruit under cold storage was investigated. Banana fruit treated with NO sustained lower chilling injury index than the control. Notably elevated nitric oxide synthetase activity and endogenous NO level were observed in NO-treated banana fruit. PAs contents in treated fruit were significantly higher than control fruit, due to the elevated activities of arginine decarboxylase and ornithine decarboxylase. NO treatment increased the activities of diamine oxidase, polyamine oxidase and glutamate decarboxylase, while reduced GABA transaminase activity to lower levels compared with control fruit, which resulted the accumulation of GABA. Besides, NO treatment upregulated proline content and significantly enhanced the ornithine aminotransferase activity. These results indicated that the chilling tolerance induced by NO treatment might be ascribed to the enhanced catabolism of PAs, GABA and proline.


Tunnelling spectra of individual magnetic endofullerene molecules.
The manipulation of single magnetic molecules may enable new strategies for high-density information storage and quantum-state control. However, progress in these areas depends on developing techniques for addressing individual molecules and controlling their spin. Here, we report success in making electrical contact to individual magnetic N@C(60) molecules and measuring spin excitations in their electron tunnelling spectra. We verify that the molecules remain magnetic by observing a transition as a function of magnetic field that changes the spin quantum number and also the existence of non-equilibrium tunnelling originating from low-energy excited states. From the tunnelling spectra, we identify the charge and spin states of the molecule. The measured spectra can be reproduced theoretically by accounting for the exchange interaction between the nitrogen spin and electron(s) on the C(60) cage.


Vitamin B6, magnesium, and combined B6-Mg: therapeutic effects in childhood autism.
This article reports the behavioral, biochemical, and electrophysiological effects of four therapeutic crossed-sequential double-blind trials with 60 autistic children: Trial A--vitamin B6 plus magnesium/magnesium; Trial B--vitamin B6 plus magnesium; Trial C--magnesium; and Trial D--vitamin B6. Therapeutic effects were controlled using behavior rating scales, urinary excretion of homovanillic acid (HVA), and evoked potential (EP) recordings. The behavioral improvement observed with the combination vitamin B6-magnesium was associated with significant modifications of both biochemical and electrophysiological parameters: the urinary HVA excretion decreased, and EP amplitude and morphology seemed to be normalized. These changes were not observed when either vitamin B6 or magnesium was administered alone.


The CHOICE survey: high rates of persistent and uncontrolled asthma in the United States.
Surveys have consistently shown that many patients with asthma do not have their disease well controlled. The CHOICE (Comprehensive Survey of Healthcare Professionals and Asthma Patients Offering Insight on Current Treatment Gaps and Emerging Device Options) survey was designed to evaluate the current status of inhalation devices used in asthma treatment, but questions also were included about asthma severity and control. A total of 1,000 patients with asthma were interviewed about their use of inhalation devices and asthma-related burden, medication use, and hospital/emergency care. Based on the responses to these questions, asthma severity and control were categorized using methods established in the Expert Panel Report III (EPR 3). Almost half (490) of the patients with asthma participating in the CHOICE survey were not using controller medications. Most of those not using controllers (79%) had persistent asthma; 47% had either mild or moderate persistent asthma. Of those on controllers (510), only 14.3% were well controlled. Acute care utilization was greater for patients with persistent asthma than those with intermittent asthma and for patients with not well and poorly controlled asthma than those with well-controlled asthma. The CHOICE survey is particularly pertinent clinically, because it demonstrates for the first time, using EPR 3 methods, the current extent of poor asthma control in the United States. This situation falls far short of national asthma management targets.


Dexmedetomidine modulates mitochondrial dynamics to protect against endotoxin-induced lung injury via the protein kinase C-ɑ/haem oxygenase-1 signalling pathway.
Endotoxin-induced acute lung injury (ALI) has a high mortality rate, and there are limited effective treatment options available. The aim of the present study was to identify if dexmedetomidine could regulate mitochondrial fusion and fission through the protein kinase C (PKC)-α/haem oxygenase (HO)-1 pathway to protect against endotoxin-induced ALI. Dexmedetomidine was administered by intraperitoneal injection once daily for three days prior to induction of lung injury to mice. Mice in the PKC-α inhibitor group received dexmedetomidine by intraperitoneal injection 1 h after each chelerythrine injection, and lipopolysaccharide was injected 1 h after the last dose of dexmedetomidine. The lung wet/dry weight ratio, oxidative stress, inflammatory response, and expression levels of PKC-α, Nrf2, HO-1, Mfn1, Mfn2, OPA1, Drp1, and Fis1 were determined. Dexmedetomidine administration attenuated lung oxidative stress, decreased inflammatory cytokines secretion, and downregulated the expression levels of Drp1 and Fis1. Moreover, dexmedetomidine increased levels of Mfn1, Mfn2, and OPA1, and alleviated endotoxin-induced lung injury. Administration of chelerythrine partially reversed the pneumoprotective effects of dexmedetomidine. Dexmedetomidine may activate the PKC-ɑ/HO-1 pathway to increase the expression of Mfn1, Mfn2, and OPA1, while decreasing Drp1 and Fis1 expression, thereby reduce endotoxin-induced acute lung injury.


Construction of Cationic Azahelicenes: Regioselective Three-Component Annulation Using In Situ Activation Strategy.
Described herein is a strategy to construct cationic azahelicenes through the three-component annulation reaction of isoquinoline, indole, and 1,2-dichloroethane (DCE), in which DCE serves as an in situ activating agent for C1-H activation of isoquinoline, a vinyl equivalent, and a solvent. This in situ activation annulation reaction features a facile one-step synthesis and complete regioselectivity. The complete regioselectivity of C1 over C3 for the isoquinoline ring paves a path to the helical structure in a highly ordered sequence. One of the synthesized ionic [5]azahelicenium fluorophores exhibits the potential to serve as a mitochondria-targeted biomarker with good photostability and low cytotoxicity.


Fidelity versus flexibility: translating evidence-based research into practice.
Understanding the process by which research is translated into practice is limited. This study sought to examine how interventions change during implementation. Data were collected from July 2005 to September 2007. A real-time and cross-case comparison was conducted, examining ten interventions designed to improve health promotion in primary care practices in practice-based research networks. An iterative group process was used to analyze qualitative data (survey data, interviews, site visits, and project diary entries made by grantees approximately every 2 weeks) and to identify intervention adaptations reported during implementation. All interventions required changes as they were integrated into practice. Modifications differed by project and by practice, and were often unanticipated. Three broad categories of changes were identified and include modifications undertaken to accommodate practices' and patients' circumstances as well as personnel costs. In addition, research teams played a crucial role in fostering intervention uptake through their use of personal influence and by providing motivation, retraining, and instrumental assistance to practices. These efforts by the research teams, although rarely considered an essential component of the intervention, were an active ingredient in successful implementation and translation. Changes are common when interventions are implemented into practice settings. The translation of evidence into practice will be improved when research design and reporting standards are modified to help quality-improvement teams understand both these adaptations and the effort required to implement interventions in practice.


Unraveling VEALYL Amyloid Formation Using Advanced Vibrational Spectroscopy and Microscopy.
Intermediate species are hypothesized to play an important role in the toxicity of amyloid formation, a process associated with many diseases. This process can be monitored with conventional and two-dimensional infrared spectroscopy, vibrational circular dichroism, and optical and electron microscopy. Here, we present how combining these techniques provides insight into the aggregation of the hexapeptide VEALYL (Val-Glu-Ala-Leu-Tyr-Leu), the B-chain residue 12-17 segment of insulin that forms amyloid fibrils (intermolecularly hydrogen-bonded β-sheets) when the pH is lowered below 4. Under such circumstances, the aggregation commences after approximately an hour and continues to develop over a period of weeks. Singular value decompositions of one-dimensional and two-dimensional infrared spectroscopy spectra indicate that intermediate species are formed during the aggregation process. Multivariate curve resolution analyses of the one and two-dimensional infrared spectroscopy data show that the intermediates are more fibrillar and deprotonated than the monomers, whereas they are less ordered than the final fibrillar structure that is slowly formed from the intermediates. A comparison between the vibrational circular dichroism spectra and the scanning transmission electron microscopy and optical microscope images shows that the formation of mature fibrils of VEALYL correlates with the appearance of spherulites that are on the order of several micrometers, which give rise to a "giant" vibrational circular dichroism effect.


Conscious awareness of self-relevant information is necessary for an incidental self-memory advantage.
Co-presenting an item with self-relevant vs. other-relevant information under a non-self-referential encoding context can produce a memory advantage. The present study examined the relative contributions of conscious vs. unconscious processing of self-cues to this incidental self-memory advantage. During encoding, the participant's own or another person's name was presented supraliminally or subliminally prior to the presentation of each target word. Consistent across two experiments, we found better memory for words preceded by the own name vs. another name but only when the names were presented supraliminally. The masked priming effect produced by the own name in Experiment 2 suggests that the absence of a self-memory advantage following subliminal name presentation was unlikely due to subliminal self-processing being too weak. Our findings suggest that conscious awareness of self-cues is necessary for an incidental self-memory advantage. Potential qualitative differences between conscious vs. unconscious self-processing mediating the impact of self on memory are discussed.


Students' understanding of "Women-Centred Care Philosophy" in midwifery care through Continuity of Care (CoC) learning model: a quasi-experimental study.
The philosophy of midwifery education is based on the 'Women-centred care' model, which provides holistic care to women. Continuity of care (CoC) is integral to the concept of holistic women-centred care and fundamental to midwifery practice. The objective of this study was to determine any differences in students' understanding of midwifery care philosophy between students who underwent the CoC learning model and those who underwent the fragmented care learning model. We used a quasi-experiment design. This study was conducted by all final year midwifery students at two schools of midwifery in Indonesia. Fifty four students from one school attended 6 months of clinical training using the CoC learning model. The control group was comprised of 52 students from the other school. These students used the conventional clinical training model (the fragmented care learning model). The independent T-test using SPSS was used to analyse the differences between the two groups of students in terms of understanding midwifey care philosophy in five aspects (personalized, holistic, partnership, collaborative, and evidence-based care). There were no significant differences between the groups before interventon. There were significant differences between the two groups after clinical training (p < 0.01). The mean post-clinical score of students using all five aspects of the CoC clinical learning model (15.96) was higher than that of the students in the control group (10.65). The CoC clinical learning model was shown to be a unique learning opportunity for students to understand the philosophy of midwifery. Being aligned with midwifery patients and developing effective relationships with them offered the students a unique view of midwifery practice. This also promoted an increased understanding of the philosophy of women-centred care. Zero maternal mortality rate was found in the experiment group. The results of this study suggest that clinical trainingwith a CoC learning model is more likely to increase students' understanding of midwifery care philosophy. This in turn improves the quality ofclinical care, thereby enhancing overall health benefits for women.


Activity and thermal stability of genetically truncated forms of Aspergillus glucoamylase.
Glucoamylase (GA) from Aspergillus awamori (EC 18.104.22.168) is a secreted starch hydrolase with a large catalytic domain (aa 1-440), a starch-binding domain (aa 513-616), and a highly O-glycosylated region of 72 aa of unknown function that links the catalytic and starch-binding domains. We have genetically engineered a series of truncated forms of GA to determine how much of the highly O-glycosylated region is necessary for the activity or stability of GAII, a fully active form of the enzyme that lacks the starch-binding domain. Mutations were made by inserting stop-codon linkers into restriction sites within the coding region of the GA gene, and mutated genes were expressed in Saccharomyces cerevisiae for analysis of the truncated enzymes. Our results show that up to 30 aa from the C-terminal end of GAII can be deleted with little effect on the activity, thermal stability, or secretion of the enzyme. Further deletions resulted in diminution or loss of enzyme activity on starch plates, and loss of detectable enzyme in culture supernatants, indicating that these residues are essential for GAII function.


Atrial fibrillation independently linked with depression in community-dwelling older population. Results from the nationwide PolSenior project.
Depression is a frequently observed comorbid condition in patients with cardiovascular diseases. In contrast to coronary heart disease and heart failure there is a limited amount of published data concerning the increased prevalence of depression among patients with atrial fibrillation (AF). Therefore, we decided to assess the prevalence of depression in Polish community-dwelling older patients with a history of AF. The data were collected as part of the nationwide PolSenior project (2007-2012). Out of 4979 individuals (age range 65-104 years), data on self-reported history of AF were available for 4677 (93.9%). Finally, 4049 participants without suspected moderate or severe dementia in Mini Mental State Examination test were assessed with the 15-item Geriatric Depression Scale (GDS), and a score of 6 points and more was regarded as suspected depression. Mean age (±SD) of the study population was 78.1 (±8.3) years; 52% were males. The history of AF was reported by 788 (19.5%) subjects. In the univariate analysis a self-reported AF history was associated with 42% increase of suspected depression (41% vs 29%; P < 0.001). In multivariate logistic regression AF remained an independent predictor of depression (OR = 1.69; 95%CI: 1.43-2.00), stronger than heart failure, diabetes or coronary heart disease. In community-dwelling geriatric Polish population AF is associated with higher prevalence of depression. This association is independent from the demographic factors, disabilities and comorbidities (including history of stroke).