Dietary supplementation with vitamin C ameliorates the adverse effects of Salmonella Enteritidis-challenge in broilers by shaping intestinal microbiota.
Salmonella Enteritidis (SE) infection is not only a leading cause of poor production performance and compromised animal welfare in broilers but also a potential threat to public health. Two experiments were conducted to evaluate the effects of dietary supplemental vitamin C (VC) on SE challenged-broilers. In experiment 1, one hundred eighty 1-day-old Arbor Acre broilers were randomly allocated into 3 treatments, with 0, 500, or 1,000 mg/kg VC included in the diet. In experiment 2, dietary VC at 0 or 500 mg/kg, with or without SE challenge was applied in a 2 × 2 factorial arrangement in 6 randomized complete blocks. In experiment 1, addition with 500 mg/kg VC increased BW and infectious bursal disease (IBD) titer of broilers on 35 D (P < 0.05), whereas 1,000 mg/kg VC had no effects on the IBD titer (P > 0.05) compared with the control group. In experiment 2, SE challenge depressed BW on 11 and 21 D (P < 0.05 and P = 0.088, respectively), whereas increased mortality and hepatic bacterial translocation (P < 0.05) on 21 D. Further, SE challenge resulted in lower villus height in jejunum, lower microbial richness, and diversity, whereas higher abundance of Enterobacteriaceae in cecum (P < 0.05). Importantly, supplementation with VC increased BW on both 21 and 35 D (P < 0.05 and P = 0.088, respectively) and enhanced the intestinal health by improving villus morphology and microbial structure as indicated by higher cecal microbial richness and Firmicutes to Bacteroidetes ratio, while lower abundance of Enterobacteriaceae (P < 0.05). In addition, birds fed with 500 mg/kg VC in the diet had significantly increased jejunal secretory immunoglobulin A levels, T lymphocytes stimulation index, and serum total antioxidant capability compared with groups without VC (P < 0.05). In conclusion, SE challenge induced lower production performance and higher mortality in broilers. However, dietary supplementation with VC ameliorated SE-caused damage in broilers by improving the intestinal health, partly mediated by shaping the structure of cecal microbiota.


Low-profile Visualized Intraluminal Support Junior Device for the Treatment of Intracranial Aneurysms.
Early case series suggest that the recently introduced Low-profile Visualized Intraluminal Support Junior (LVIS Jr.) device (MicroVention-Terumo, Inc., Tustin, CA) may be used to treat wide-necked aneurysms that would otherwise require treatment with intrasaccular devices or open surgery. We report our single-center experience utilizing LVIS Jr. to treat intracranial aneurysms involving 1.8-2.5 mm parent arteries. We retrospectively reviewed records of patients treated with the LVIS Jr. device for intracranial aneurysms at a single center. A total of 21 aneurysms were treated in 18 patients. Aneurysms were 2-25 mm in diameter; one was ruptured, while three had recurred after previous rupture and treatment. Lesions were distributed across the anterior (n=12) and posterior (n=9) circulations. Three were fusiform morphology. Stent deployment was successful in 100% of cases with no immediate complications. Seventeen aneurysms were treated with stent-assisted coil embolization resulting in immediate complete occlusion in 94% of cases. Two fusiform aneurysms arising from the posterior circulation were further treated with elective clip ligation after delayed expansion and recurrence; no lesions required further endovascular treatment. Four aneurysms were treated by flow diversion with stand-alone LVIS Jr. stent, and complete occlusion was achieved in three cases. Small foci of delayed ischemic injury were noted in two patients in the setting of antiplatelet medication noncompliance. No in-stent stenosis, migration, hemorrhage, or permanent deficits were observed. Good functional outcome based on the modified Rankin Scale score (mRS ≤ 2) was achieved in 100% of cases. Our midterm results suggest that the LVIS Jr. stent may be used for a variety of intracranial aneurysms involving small parent arteries (1.8-2.5 mm) with complete angiographic occlusion, parent vessel preservation, and functional clinical outcomes. This off-label expansion would increase the number of aneurysms amenable to endovascular treatment. Future studies may build upon our experiences with flow diversion and treatment of complex or multiple lesions.


Bendopnoea in exercise limited patients with COPD.
Dyspnoea on bending over (bendopnoea) is most commonly associated with systolic heart failure. COPD patients often also complain of bendopnoea but little is known about this symptom in this patient group. We objectively assessed 44 COPD patients attending pulmonary rehabilitation for bendopnoea in a tertiary referral centre to determine the potential mechanism and clinical implications of this symptom. Bendopnoea was assessed by timing the duration of onset to breathlessness on bending forward at the waist for 30 s. BORG score, oxygen saturations and blood pressure measurements were obtained before and after. Of 44 patients (mean age±SD 66.7 ± 8.4 years; 22 male, BMI 28.1 ± 6.4), bendopnoea was present in 23 (52.3%) patients. This was significantly associated with a lower FEV1% (p = 0.02) and TLCO% (<0.001) and higher CAT score (p = 0.03). A strong trend was also noted with higher waist/hip ratio (p = 0.06). There were no associations with age, BMI, oxygen saturation, static lung volumes, exercise capacity or non-invasive haemodynamic markers such as pro-BNP, physiological changes or echocardiography findings.


Long-term impact of the low-FODMAP diet on gastrointestinal symptoms, dietary intake, patient acceptability, and healthcare utilization in irritable bowel syndrome.
The low-FODMAP diet is a frequently used treatment for irritable bowel syndrome (IBS). Most research has focused on short-term FODMAP restriction; however, guidelines recommend that high-FODMAP foods are reintroduced to individual tolerance. This study aimed to assess the long-term effectiveness of the low-FODMAP diet following FODMAP reintroduction in IBS patients. Patients with IBS were prospectively recruited to a questionnaire study following completion of dietitian-led low-FODMAP education. At baseline and following FODMAP restriction (short term) only, gastrointestinal symptoms were measured as part of routine clinical care. Following FODMAP reintroduction, (long term), symptoms, dietary intake, acceptability, food-related quality of life (QOL), and healthcare utilization were assessed. Data were reported for patients who continued long-term FODMAP restriction (adapted FODMAP) and/or returned to a habitual diet (habitual). Of 103 patients, satisfactory relief of symptoms was reported in 12% at baseline, 61% at short-term follow-up, and 57% at long-term follow-up. At long-term follow-up, 84 (82%) patients continued an 'adapted FODMAP' diet (total FODMAP intake mean 20.6, SD 14.9 g/d) compared with 19 (18%) of patients following a 'habitual' diet (29.4, SD 22.9 g/d, P=.039). Nutritional adequacy was not compromised for either group. The 'adapted FODMAP' group reported the diet cost significantly more than the 'habitual' group (P<.001) and affected social eating (P<.01) but there was no effect on food-related QOL. Healthcare utilization was similar between both groups. Low-FODMAP education is effective for long-term IBS management, enables a nutritionally adequate diet, and is broadly acceptable to patients.


Production of human metabolites of cyclosporin A, AM1, AM 4 N and AM 9, by microbial conversion.
In humans, cyclosporin A (CyA) is primarily metabolized to two hydroxylated (AM1 and AM 9) and one N-demethylated (AM 4 N) derivative. To produce these derivatives, 1237 actinomycetes were screened for their ability to convert CyA. Among them, 89 strains (7.2%) produced these derivatives from CyA. Finally, Dactylosporangium variesporum IFO 14104, Actinoplanes sp. ATCC 53771 and Streptosporangium sp. AF 935 were selected for the production of AM1, AM 4 N, and AM 9, respectively. Composition of the production medium and the incubation period with CyA were important for obtaining a high yield of CyA derivatives. Large-scale microbial conversion of CyA (1.5 g) using a 30-l jar fermentor yielded 288 mg of AM1 (19.2%), 147 mg of AM 4 N (9.8%) and 115 mg of AM 9 (7.7%).


Initial experience of robotic nephron sparing surgery in cases of high renal nephrometry scores.
The renal nephrometry scoring (RNS) system enables prediction the feasibility of nephron-sparing surgery (NSS) in renal masses. There is insufficient data regarding the outcome of robot-assisted NSS in tumors with RNS ≥10. We reviewed the trifecta outcomes of patients undergoing robotic NSS with high RNS and compare it with tumors of low and intermediate RNS. Our prospectively maintained data of all robot-assisted NSS were reviewed, and those with RNS of ≥10 were identified. Patient data, outcomes and postoperative estimated glomerular filtration rate were compared between high, intermediate and low RNS patients. In high RNS group, the mean age of the patients was 53 years (male:female = 15:3). Mean diameter of tumors was 6.28 cm (3.0-10.5 cm). Mean operative time was 173.61 ± 52.66 min and mean warm ischemia time was 27.85 ± 5.27 min. Mean estimated blood loss (EBL) was 363.89 ± 296.45 ml. Mean hospital length of stay was 5.39 ± 1.91 days (3-9 days). When compared with low and intermediate RNS, only EBL and need for pelvicalyceal system repair was significantly higher in high RNS group. Postoperative complications, renal function preservation and oncological outcomes at 3 months were comparable in all the three groups. Robot-assisted NSS is feasible with comparable outcomes in tumors with high RNS.


Granulocyte macrophage--colony-stimulating factor-dependent proliferation is impaired in macrophages from senescence-accelerated mice.
A senescence-accelerated (SAMP8) mouse model was used to determine the effect of aging on the immune system. We produced in vitro bone marrow-derived macrophages from SAMP8 mice and compared them against senescence-resistant, long-lived mice (SAMR1). Although macrophages from both strains of mice proliferated in a similar manner in response to monocyte-colony-stimulating factor (M-CSF), SAMP8 macrophages showed an impaired response to granulocyte macrophage-colony-stimulating factor (GM-CSF). Similar levels of external regulated kinases (ERK)1/2 and signaling transducer and activator of transcription 5 (STAT5) phosphorylation were observed in macrophages from both strains of mice. The lack of proliferation was not caused by the induction of apoptosis. Differentiation of bone marrow cells into dendritic cells was similar in both strains of mice, as was the induction of major histocompatibility complex (MHC) class II molecules by interferon-gamma (IFN-gamma). Finally, we determined the density of Langerhans cells in vivo in the skin of the two mouse strains, but no differences were found.


[Ultrasound echographic imaging and measurement of the amniotic cavity and yolk sac in early pregnancy: comparative study of intact and disordered pregnancies].
The chorionic cavity, vertex-breech length, yolk sac, and amnion were systematically demonstrated and measured in 50 early pregnancies, i.e., between the end of the sixth and the tenth week of gestation post menstruationem (p.m.). This was done in 23 cases with clinically and sonographically intact pregnancies without symptoms of abortion, in 12 cases with living embryos with symptoms of abortion, and in 15 cases of retained miscarriage. The thin amniotic membrane is sonographically demonstrated as a narrow, sharply defined reflected band in the chorionic cavity. In addition to direct demonstration of the amniotic membrane, the amniotic cavity can be demonstrated by a density difference in the echogenicity of the chorionic and amniotic fluids. While there are delicate, homogenously distributed inner echoes in the chorionic cavity, the amniotic cavity is empty save for the embryo structure. Sonographically, therefore, the amniotic cavity stands out as a spherical structure within the chorionic cavity. In all pregnancies with a living embryo it was possible to demonstrate the yolk sac sonographically as a sharply defined ring structure in the chorionic cavity. In 10 of the 15 cases of retained miscarriage only a rudimentary remnant of the yolk sac could be detected. The development of the amniotic and chorionic cavities and vertex-breech length was constant in the pregnancies with living embryos, the amnion developing synchronously with the vertex-breech length.(ABSTRACT TRUNCATED AT 250 WORDS)


Significance of antinuclear antibodies and rheumatoid factor in patients with advanced peripheral arterial disease.
To determine whether or not elevated titers of antinuclear antibodies (ANA) and/or rheumatoid factor (RF) are associated with patients with advanced peripheral arterial disease (PAD). A cross-sectional study was done between September 2005 and December 2006. Fifty-eight patients with clinical and angiographic evidence of PAD and 41 controls were studied. Controls had no documented history of peripheral, coronary or cerebral vascular disease. All subjects were screened for metabolic syndrome and C-reactive protein (CRP) as risk factors for peripheral vascular disease. Additionally, all were tested for anti-mitochondrial, anti-neutrophil cytoplasmic and anti-smooth muscle antibodies; those with positive results were excluded. ANA and RF were measured in sera from cases and controls. One case and 3 controls had positive anti-smooth muscle antibodies and were therefore excluded from statistical analysis. Metabolic syndrome was significantly more prevalent in patients than controls (p<0.05). Mean CRP level was 4.78+/-7.70 and 2.65+/-3.86 mg/dl in cases and controls, respectively (p=0.021). ANA were detected at a titer of >or=1:40 in 6 (10.5%) of the advanced PAD patients but none of the controls; the difference was not statistically significant. RF was less prevalent in cases than controls (p<0.05). RF and ANA do not appear to be associated with PAD in a Kuwaiti population.


Solution-processed parallel tandem polymer solar cells using silver nanowires as intermediate electrode.
Tandem architecture is the most relevant concept to overcome the efficiency limit of single-junction photovoltaic solar cells. Series-connected tandem polymer solar cells (PSCs) have advanced rapidly during the past decade. In contrast, the development of parallel-connected tandem cells is lagging far behind due to the big challenge in establishing an efficient interlayer with high transparency and high in-plane conductivity. Here, we report all-solution fabrication of parallel tandem PSCs using silver nanowires as intermediate charge collecting electrode. Through a rational interface design, a robust interlayer is established, enabling the efficient extraction and transport of electrons from subcells. The resulting parallel tandem cells exhibit high fill factors of ∼60% and enhanced current densities which are identical to the sum of the current densities of the subcells. These results suggest that solution-processed parallel tandem configuration provides an alternative avenue toward high performance photovoltaic devices.


Neuron-specific responses to acetylcholine within the spinal dorsal horn circuits of rodent and primate.
Excitatory and inhibitory neurotransmission within the spinal dorsal horn is tightly controlled to regulate transmission of nociceptive signals to the brain. One aspect of this control is modulation of neuronal activity through cholinergic signaling. Nociceptive neurons in the dorsal horn express both nicotinic and muscarinic cholinergic receptors and activation of these receptors reduces pain in humans, while inhibition leads to nociceptive hypersensitivity. At a cellular level, acetylcholine (ACh) has diverse effects on excitability which is dependent on the receptor and neuronal subtypes involved. In the present study we sought to characterize the electrophysiological responses of specific subsets of lamina II interneurons from rat and marmoset spinal cord. Neurons were grouped by morphology and by action potential firing properties. Whole-cell voltage-clamp recordings from lamina II dorsal horn neurons of adult rats showed that bath applied acetylcholine increased, decreased or had no effect on spontaneous synaptic current activity in a cell-type specific manner. ACh modulated inhibitory synaptic activity in 80% of neurons, whereas excitatory synaptic activity was affected in less than 50% of neurons. In whole-cell current clamp recordings, brief somatic application of ACh induced cell-type specific responses in 79% of rat lamina II neurons, which included: depolarization and action potential firing, subthreshold membrane depolarization, biphasic responses characterized by transient depolarization followed by hyperpolarization and membrane hyperpolarization alone. Similar responses were seen in marmoset lamina II neurons and the properties of each neuron group were consistent across species. ACh-induced hyperpolarization was blocked by the muscarinic antagonist atropine and all forms of acetylcholine-induced depolarization were blocked by the nicotinic antagonist mecamylamine. The cholinergic system plays an important role in regulating nociception and this study contributes to our understanding of how circuit activity is controlled by ACh at a cellular level in primate and rodent spinal cord.


Enol formation and ring-opening in OH-initiated oxidation of cycloalkenes.
Photolytic OH-initiated oxidation of cyclopentene, cyclohexene, and 1,4-cyclohexadiene have been investigated by using tunable synchrotron photoionization mass spectrometry. Electronic structure calculations (CBS-QB3) are employed in Franck-Condon (FC) spectral simulations of the photoionization efficiency curves (PIE) of the observed products. Cyclopentenol (cyclopenten-1-ol, 1-c-C(5)H(7)OH) and its isomers cyclopenten-2-ol (2-c-C(5)H(7)OH) and cyclopentanone (c-C(5)H(8)=O), are detected from OH-initiated cyclopentene oxidation. The measured adiabatic ionization energy (AIE) of 1-c-C(5)H(7)OH is 8.4(+/-0.1) eV, and that of 2-c-C(5)H(7)OH is 9.5(+/-0.1) eV. The calculated AIE of possible cyclopentene oxidation products cis-1,2-epoxycyclopentane and 2,3-epoxycyclopentanol is 9.97 and 9.44 eV, respectively. Product spectra from OH-initiated oxidation of cyclohexene and cyclohexa-1,4-diene show a substantial contribution from linear aldehydes, indicating a prominent role for ring opening. Implications for the oxidation chemistry of cycloalkenes are briefly discussed.


DC-LAMP+ dendritic cells are recruited to gastric lymphoid follicles in Helicobacter pylori-infected individuals.
Infection with Helicobacter pylori is associated with development of ulcer disease and gastrointestinal adenocarcinoma. The infection leads to a large infiltration of immune cells and the formation of organized lymphoid follicles in the human gastric mucosa. Still, the immune system fails to eradicate the bacteria, and the substantial regulatory T cell (Treg) response elicited is probably a major factor permitting bacterial persistence. Dendritic cells (DCs) are professional antigen-presenting cells that can activate naive T cells, and maturation of DCs is crucial for the initiation of primary immune responses. The aim of this study was to investigate the presence and localization of mature human DCs in H. pylori-infected gastric mucosa. Gastric antral biopsy specimens were collected from patients with H. pylori-associated gastritis and healthy volunteers, and antrum tissue was collected from patients undergoing gastric resection. Immunohistochemistry and flow cytometry showed that DCs expressing the maturation marker dendritic cell lysosome-associated membrane glycoprotein (DC-LAMP; CD208) are enriched in the H. pylori-infected gastric mucosa and that these DCs are specifically localized within or close to lymphoid follicles. Gastric DC-LAMP-positive (DC-LAMP(+)) DCs express CD11c and high levels of HLA-DR but little CD80, CD83, and CD86. Furthermore, immunofluorescence analyses demonstrated that DC-LAMP(+) DCs are in the same location as FoxP3-positive putative Tregs in the follicles. In conclusion, we show that DC-LAMP(+) DCs with low costimulatory capacity accumulate in the lymphoid follicles in human H. pylori-infected gastric tissue, and our results suggest that Treg-DC interactions may promote chronic infection by rendering gastric DCs tolerogenic.


Heterogeneous photo-Fenton degradation of acid red B over Fe2O3 supported on activated carbon fiber.
Fe2O3 supported on activated carbon fiber (Fe2O3/ACF) was prepared via an impregnation method and characterized by X-ray diffraction, scanning electron microscopy and BET analysis. The results indicated that Fe2O3 with small particle size was highly dispersed on the surface of the ACF and the introduction of Fe2O3 did not change the ACF pore structure. Fe2O3/ACF exhibited a higher Fenton efficiency for the degradation of acid red B (ARB), especially under simulated solar irradiation. Complete decoloration of the ARB solution and 43% removal of TOC could be achieved within 200 min under optimal conditions. It was verified that more ˙OH radicals were generated in the photo-assisted Fenton process and involved as active species in ARB degradation. FTIR analysis indicated that the degradation of ARB was initiated through the cleavage of -N=N-, followed by hydroxylation and opening of phenyl rings to form aliphatic acids, and further oxidation of aliphatic acids would produce CO2 and H2O. Moreover, Fe2O3/ACF maintained its activity after being reused 4 times and the release of iron from the catalyst was found to be insignificant during the Fenton and photo-Fenton processes, indicating that Fe2O3/ACF had good long-term stability.


Mimics and magnets: the importance of color and ecological facilitation in floral deception.
Plants that lack floral rewards can attract pollinators if they share attractive floral signals with rewarding plants. These deceptive plants should benefit from flowering in close proximity to such rewarding plants, because pollinators are locally conditioned on floral signals of the rewarding plants (mimic effect) and because pollinators are more abundant close to rewarding plants (magnet effect). We tested these ideas using the non-rewarding South African plant Eulophia zeyheriana (Orchidaceae) as a study system. Field observations revealed that E. zeyheriana is pollinated solely by solitary bees belonging to a single species of Lipotriches (Halictidae) that appears to be closely associated with the flowers of Wahlenbergia cuspidata (Campanulaceae), a rewarding plant with which the orchid is often sympatric. The pale blue color of the flowers of E. zeyheriana differs strongly from flowers of its congeners, but is very similar to that of flowers of W. cuspidata. Analysis of spectral reflectance patterns using a bee vision model showed that bees are unlikely to be able to distinguish the two species in terms of flower color. A UV-absorbing sunscreen was applied to the flowers of the orchid in order to alter their color, and this resulted in a significant decline in pollinator visits, thus indicating the importance of flower color for attraction of Lipotriches bees. Pollination success in the orchid was strongly affected by proximity to patches of W. cuspidata. This was evident from one of two surveys of natural populations of the orchid, as well as experiments in which we translocated inflorescences of the orchid either into patches of W. cuspidata or 40 m outside such patches. Flower color and location of E. zeyheriana plants relative to rewarding magnet patches are therefore key components of the exploitation by this orchid of the relationship between W. cuspidata and Lipotriches bee pollinators.


Recrudescence of cervical dysplasia among women who are infected with the human immunodeficiency virus: a case-control analysis.
The purpose of this study was to compare the recurrence rates of cervical dysplasia after ablation therapy and hysterectomy for women who are positive for the human immunodeficiency virus and for women who are negative for the human immunodeficiency virus. Forty-three women who were positive for the human immunodeficiency virus were compared with 103 patients who were negative for the human immunodeficiency virus after cryotherapy, laser ablation, loop electrosurgical excision procedure, conization, and hysterectomy for cervical dysplasia. All patients were followed up for at least 24 months. Patients with preexisting cervical cancer or with positive margins after treatment were excluded. Recurrence was higher in the HIV positive group for all modalities (73% vs 27%; P =.019). Higher recurrence rates were seen with CD4 counts <200 cells/mm3 (55% vs 26%). Hysterectomy fared better than standard therapy (50% vs 86%), but recurrences were significant.


Expression of p65 gene in experimental colon cancer under the influence of 5-fluorouracil given alone and in combination with hormonal modulation.
The effect of tamoxifen (TAM), lanreotide (LAN) and 5-fluorouracil (5-FU), given separately or together, on p65 gene expression in murine Colon 38 cancer was investigated by RT-PCR method. The findings were compared with cell proliferation determined by bromodeoxyuridine (BrdU) labeling index, apoptosis visualized by TUNEL method and tumor mass. It was found that in the control group (mice bearing colon cancer without treatment) the expression of p65 gene was present in 57% of investigated samples. In the groups treated with TAM or LAN p65 gene expression was detected in 87.5% and 83.3% of analyzed cases, respectively. Both these substances increased apoptotic index in Colon 38 cancer and LAN also decreased the proliferation index. After a combined treatment with TAM and LAN a percentage of p65 positive cases was similar to that of the control group and equaled approximately 60%. This treatment did not increase proapoptotic effects of these drugs, and even reduced the antiproliferogenic effect of LAN. In the group treated with 5-FU and LAN p65 gene expression was also close to the control value (about 66%). Similarly in this group the combined treatment with these two drugs did not cause any favorable effect on proliferation and apoptosis. Moreover, in this group even reduced antiproliferogenic effect of LAN was observed. In the group with 5-FU alone the expression of p65 was present in about 80% of samples. The treatment with 5-FU increased apoptotic index and did not change proliferation. In the group treated with a combination of TAM and 5-FU all analyzed cases showed the presence of p65 gene expression. Previously, we observed in this group the most pronounced and synergistic effect of these substances on the inhibition of cell proliferation and tumor mass reduction. Based on these findings we conclude that p65 gene expression in murine Colon 38 cancer tissues can be modulated via chemotherapy (5-FU) and also via hormonal modulation (TAM and LAN).


Primary Cardiac Synovial Sarcoma Originating From the Mitral Valve Causing Left Ventricular Outflow Tract Obstruction.
An 11-year-old boy was admitted with complaints of syncope and convulsion. Echocardiogram revealed a mass measuring 2 × 4 cm related to the mitral subvalvular apparatus. The mass, which appeared to be attached to the anterolateral papillary muscle, protruded into the left ventricular outflow tract causing intermittent obstruction. The patient underwent surgical excision of the mass. Pathology confirmed the diagnosis of primary synovial sarcoma. At six months following the operation, a small mass measuring 1 × 1 cm was detected in the left ventricle. The patient underwent reoperation consisting of radical resection of the subvalvular apparatus and mitral valve replacement. Histology confirmed that the mass was cardiac synovial sarcoma. One year after surgery, the patient is doing well.


Depression in systemic lupus erythematosus: gender differences in the performance of the Beck Depression Inventory (BDI), Center for Epidemiologic Studies Depression Scale (CES-D), and Hospital Anxiety and Depression Scale (HADS).
The prevalence of depressive symptoms in patients with systemic lupus erythematosus (SLE) varies widely between different cohorts (17-75%), primarily due to factors such as the heterogeneity of the samples and the instruments used to detect depressive symptoms. Most of these instruments are self-administered questionnaires that have different characteristics and approaches to depressive symptoms. This study aimed to evaluate gender differences in the performance of three questionnaires used to assess depressive symptoms in patients with SLE: the Beck Depression Inventory (BDI), Center for Epidemiologic Studies Depression Scale (CES-D), and Hospital Anxiety and Depression Scale (HADS). This study included 54 male and 54 female SLE patients. Depressive symptoms were assessed using BDI (cutoffs 13 and 15), CES-D and HADS. The gold standard method used was the diagnostic criteria of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. Regarding the performance of the BDI questionnaire, no significant differences in sensitivity or specificity were found between the genders. The specificity of the CES-D questionnaire was significantly greater for the male group (83% vs. 62.5%, p = 0.0309), and its sensitivity was non-significantly higher for the female group (92.9% for women and 71.4% for men; p = 0.2474). Regarding the performance of the HADS, we found similar sensitivities between the genders (71.4%) but a higher specificity among the men (95.7% in men and 82.5% in women, p = 0.0741). In conclusion, our results suggest the presence of gender differences in the performance of the questionnaires in SLE patients. The BDI had the most similar performances between the male and female groups. In contrast, the CES-D and HADS-D showed considerable variation in performances between men and women with SLE.


Student-Teacher Relationship: Its Measurement and Effect on Students' Trait, Performance, and Wellbeing in Private College.
Student-teacher relationships (STRs) have been examined by many studies. However, an omission still exists, the existing scales are not appropriate for studying STRs in private colleges because of the special character of these schools. This paper presents the development and validation of Private-College Student-Teacher Relationship Scale (PCSTRS), the first instrument to evaluate student-teacher relationships (STRs) in private colleges. The PCSTRS has six dimensions: trust, interaction, intimacy, care, approval, and comfort. In our main study, the validity and reliability of the six-factor PCSTRS model were demonstrated. The result of internal consistency coefficient indicated the high reliability of the scale, and the result of concurrent validity indicated the significant correlational relationships between the PCSTRS with other STR measures. In supplementary study, the PCSTRS was administered to 360 participants to confirm the applicability of PCSTRS and investigate the relation of STRs and students' traits, performance, and wellbeing, as well as the differences between the private school and the public school in this relation; the analyses revealed that there were significant differences in trust, intimacy, and care between private and public colleges; positive correlations were found between STRs and self-esteem, self-efficacy, academic performance, extracurricular activity involvement, and subjective wellbeing. Present research firstly develops the PCSTRS, examined the reliability and validity, and provides the proposed nomological network among related constructs.


Peripheral corneal grafts in Terrien's marginal degeneration.
Surgical treatment of two cases of Terrien's marginal degeneration is discussed. Because of the peripheral location of the corneal thinning, free-hand grafting is required. The procedure and its complications, both intraoperative and postoperative, are described in detail.


Dissociable effects of age and testosterone on adolescent impatience.
The onset of adolescence is associated with an increase in transgressive behaviours-from juvenile delinquency to substance use and unprotected sex-that are often attributed to increased impulsiveness. In the past, this increase was ascribed to "raging hormones"; more recently, to an imbalance in the maturation of different brain regions. However, it remains unclear how these large-scale biological changes impact specific processes that result in impulsive decisions, namely, sensitivity to immediate rewards and general discounting of future options. To gain further insight into these questions, we used an intertemporal choice task to investigate the role of testosterone in impatient decision-making in boys at the developmental transition to adolescence (N=72, ages 11-14). Our results suggest that increased testosterone (but not age) is related to increased sensitivity to immediate rewards, whereas increased age (but not testosterone) is related to a reduction in general impatience. These results are discussed in the context of recent neurobiological models of adolescent development.


REPRODUCTIVE BEHAVIOR OF FEMALE BUNTINGS: ISOLATING MECHANISMS IN A HYBRIDIZING PAIR OF SPECIES.
The plumage characteristics of male Indigo and Lazuli Buntings are distinct, but the two species can learn each other's songs. Populations comprising Indigo, Lazuli and hybrid individuals occur in the Great Plains of North America, and assortative mating has been inferred from morphometric data. We devised a laboratory assay for determining female preferences for visual and vocal characteristics of conspecific and heterospecific males and for mixtures of these characteristics, such as might be encountered in an overlap population. Females of both species gave more copulation-solicitation displays when exposed to conspecific plumage and vocalizations than when exposed to heterospecific plumage and vocalizations. Females gave intermediate and similar responses to the combinations of conspecific plumage with heterospecific vocalizations and heterospecific plumage with conspecific vocalizations. Thus, in the absence of other potentially important variables, female reproductive behavior is consistent with the hypothesis of assortative mating, based upon both vocal and visual traits of the males and caused by female choice in this semispecies pair.


Seasonal changes in immunoreactivity of vascular endothelial factor and its receptors VEGFR1 and VEGFR2 in the uterus of wild ground squirrels (Citellus dauricus Brandt).
In this study, we investigated the immunoreactivity of vascular endothelial growth factor (VEGF) and its receptors flt-1 (VEGFR1) and the kinase domain receptor (KDR/Flk-1, VEGFR2) in the uteri of the wild ground squirrels during the estrous period, early pregnancy and nonbreeding period. Cellular localizations of VEGF, VEGFR1 and VEGFR2 were detected by immunohistochemistry, and total proteins were extracted from uterine tissue in the estrous period, early pregnancy and nonbreeding period for Western blotting analysis. In addition, plasma estradiol-17β and progesterone concentrations were measured by radioimmunoassay. Stronger positive staining of VEGF was found in luminal epithelial cells and glandular cells, and its receptors (VEGFR1 and VEGFR2) were observed in stromal cells in the estrous period and early pregnancy compared with the nonbreeding period. The protein levels of VEGF, VEGFR1 and VEGFR2 were significantly higher in the estrous period and early pregnancy as compared with the nonbreeding period. Besides, plasma estradiol-17β and progesterone concentrations were higher in the estrous period and early pregnancy than in the nonbreeding period, suggesting that the immunoreactivities of VEGF, VEGFR1 and VEGFR2 were correlated with changes in plasma estradiol-17β and progesterone concentrations. These results suggested that VEGF and its receptors may be involved in the regulation of seasonal changes in the uterine functions of wild female ground squirrels.


[The treatment of mandibular fractures, complicated by inflammations in the fracture area, by means of xenogenic cartilage].
The authors used a personal technique for the management of infected jaw fractures. If the fracture cleft was not wider than 1 cm, they performed a surgical revision (having made an incision through the mucoperiosteum of the oral vestibule) and replaced the excochleated gra-ulation tissue (including sequestrums) by lyophilized cartilage. The bone fragments were immoblized by bone sutures previously applied and also by additional plastic splints. The substitution of the cartilage by bone begun 6-8 weeks after the surgical intervention (as evidenced by radiographs); the process had terminated in about 6-10 months, the implanted cartilage being completely replaced by newly formed bone. The observation involved 16 cases. The method is also recommended for treatment on an out-patient basis.


Double-twist Möbius aromaticity in a 4n+ 2 electron electrocyclic reaction.
One transition state for the 10 electron (4n+ 2) electrocyclisation of Z,E,Z-decapentaene is predicted to have the properties of a double-twist Möbius strip, with delocalised bond lengths and the NICS(0) magnetic index typical of aromaticity; a 5,6-di-(t)Bu substituted decapentaene is predicted to react in this mode in preference to the competitive six-electron electrocyclisation.


Peritraumatic physical symptoms and the clinical trajectory of PTSD after a terrorist attack: a network model approach.
Introduction: Following a mass casualty event, such as the Paris terrorist attacks of 13 November 2015, first responders need to identify individuals at risk of PTSD. Physical peritraumatic symptoms involving the autonomic nervous system may be useful in this task.Objective: We sought to determine the trajectory of physical response intensity in individuals exposed to the Paris terrorist attacks using repeated measures, and to examine its associations with PTSD. Using network modelling, we examined whether peritraumatic physical symptom associations differed by PTSD status.Methods: Physical reactions were assessed using the Subjective Physical Reactions Scale at three time points: peritraumatic by retrospective recall, then current at one year (8-18 months) and three years (30-42 months) after the attacks. Interaction networks between peritraumatic physical reactions were compared according to PTSD status.Results: On the one hand, the reported intensity of physical reactions was significantly higher in the PTSD group at all time points. On the other hand, using the dynamic approach, more robust positive interactions between peritraumatic physical reactions were found in the PTSD group one and three years after the attacks. Negative interactions were found in the no-PTSD group at one year. Peritraumatic physical numbness was found to be the most central network symptom in the PTSD group, whereas it was least central in the no-PTSD group.Discussion: Network analysis of the interaction between peritraumatic physical subjective responses, particularly physical numbness, may provide insight into the clinical course of PTSD. Our knowledge of the brain regions involved in dissociation supports the hypothesis that the periaqueductal grey may contribute to the process leading to physical numbing.Conclusions: Our findings highlight the role of peritraumatic somatic symptoms in the course of PTSD. Peritraumatic physical numbness appears to be a key marker of PTSD and its identification may help to improve early triage.


Spinal intradural extramedullary cavernous angioma. Case report.
The spinal intradural extramedullary cavernous angioma is a rare clinical entity. Only 20 surgically treated cases have been reported. The authors report on an additional case in which the lesion was located in the cervical region, and they summarize its unique clinical features. Intradural extramedullary cavernous angiomas occur predominantly in males, in the lower thoracolumbar region, exhibit a relatively high association with subarachnoid hemorrhage, and mostly adhere to the nerve root or spinal cord. Because resection is possible without causing morbidity and because outcome depends on the severity of preoperative neurological dysfunction, precise diagnosis and timely treatment are mandatory.


Soybean glycinin decreased growth performance, impaired intestinal health, and amino acid absorption capacity of juvenile grass carp (Ctenopharyngodon idella).
The present study evaluated the influence of dietary soybean glycinin on growth performance, intestinal morphology, free intestinal amino acid (AA) content, and intestinal AA transporter (AAT) mRNA levels in juvenile grass carp (Ctenopharyngodon idella). Results were displayed as follows: (1) 8% dietary glycinin decreased growth performance, inhibited intestinal growth, and caused intestinal histology damage of grass carp; (2) dietary glycinin decreased the content of free neutral AAs including Val, Ser, Tyr, Ala, Pro, and Gln in all intestinal segments, and Thr, Ile, Leu, Phe, and Gly in the MI and DI while downregulated the mRNA levels of corresponding transporters including SLC38A2, SLC6A19b, and SLC6A14 in all intestinal segments, and SLC7A5, SLC7A8, and SLC1A5 in the MI and DI. Dietary glycinin decreased the content of free basic AAs including Arg in the MI and DI and His in all intestinal segments while downregulated cationic AAT SLC7A1 mRNA levels in the MI and DI. Dietary glycinin decreased the content of free acidic AAs including Glu in all intestinal segments and Asp in the MI and DI while decreased mRNA levels of corresponding transporters including SLC1A2a in all intestinal segments and SLC1A3 in the MI and DI; (3) the digestion trial showed that basic subunits of glycinin was hard to digest in the intestine of grass carp; (4) co-administration of glutamine with glycinin partially alleviated the negative effects. Overall, glycinin decreased intestinal AA absorption capacity partly contributed by decreased AATs' mRNA levels and the indigestibility of glycinin.


Temporal bone radiology report classification using open source machine learning and natural langue processing libraries.
Radiology reports are a rich resource for biomedical research. Prior to utilization, trained experts must manually review reports to identify discrete outcomes. The Audiological and Genetic Database (AudGenDB) is a public, de-identified research database that contains over 16,000 radiology reports. Because the reports are unlabeled, it is difficult to select those with specific abnormalities. We implemented a classification pipeline using a human-in-the-loop machine learning approach and open source libraries to label the reports with one or more of four abnormality region labels: inner, middle, outer, and mastoid, indicating the presence of an abnormality in the specified ear region. Trained abstractors labeled radiology reports taken from AudGenDB to form a gold standard. These were split into training (80 %) and test (20 %) sets. We applied open source libraries to normalize and convert every report to an n-gram feature vector. We trained logistic regression, support vector machine (linear and Gaussian), decision tree, random forest, and naïve Bayes models for each ear region. The models were evaluated on the hold-out test set. Our gold-standard data set contained 726 reports. The best classifiers were linear support vector machine for inner and outer ear, logistic regression for middle ear, and decision tree for mastoid. Classifier test set accuracy was 90 %, 90 %, 93 %, and 82 % for the inner, middle, outer and mastoid regions, respectively. The logistic regression method was very consistent, achieving accuracy scores within 2.75 % of the best classifier across regions and a receiver operator characteristic area under the curve of 0.92 or greater across all regions. Our results indicate that the applied methods achieve accuracy scores sufficient to support our objective of extracting discrete features from radiology reports to enhance cohort identification in AudGenDB. The models described here are available in several free, open source libraries that make them more accessible and simplify their utilization as demonstrated in this work. We additionally implemented the models as a web service that accepts radiology report text in an HTTP request and provides the predicted region labels. This service has been used to label the reports in AudGenDB and is freely available.


Body composition and endocrine function in women with acquired immunodeficiency syndrome wasting.
The acquired immunodeficiency syndrome (AIDS) wasting syndrome is a devastating complication of human immunodeficiency virus (HIV) infection characterized by progressive weight loss and severe inanition. In men, the wasting syndrome is characterized by a disproportionate decrease in lean body mass and relative fat sparing. In contrast, relatively little is known about the gender-specific changes in body composition that characterize AIDS wasting in women. Three groups of women were studied to determine body composition and hormonal changes with respect to stage of wasting [nonwasting (NW; weight >90% ideal body weight; weight loss <10% of preillness maximum; n = 12), early wasting (EW; weight >90% ideal body weight; weight loss >10% of preillness maximum; n = 10), and late wasting (LW; weight <90%; n = 9)] and compared with a control group of 12, healthy, age-matched women. Weight loss averaged 6 +/- 6% (NW), 15 +/- 6% (EW), and 20 +/- 8% (LW) in the three groups. Lean, fat, and muscle masses were determined by dual energy x-ray absorptiometry and urinary creatinine excretion. Subjects were 36 +/- 5 yr of age (mean +/- SD) with a CD4 cell count of 379 +/- 239 cells/mm3. The body mass index was 24.4 +/- 2.6 kg/m2 (NW), 22.2 +/- 1.2 kg/m2 (EW), 18.2 +/- 2.0 kg/m2 (LW), and 24.3 +/- 2.6 kg/m2 (controls; P < 0.01, NW vs. EW; P < 0.0001, NW vs. LW). Lean body mass indexed for height was 15.7 +/- 2.4 kg/m2 (NW), 14.8 +/- 2.0 kg/m2 (EW), and 13.7 +/- 1.2 kg/m2 (LW) and was decreased significantly only in the LW group (P < 0.05 vs. NW). Muscle mass was 96% (NW), 94% (EW), and 78% (LW) of that predicted for height (P < 0.05, NW vs. LW). In contrast, fat mass indexed for height was decreased significantly among patients in both the EW and LW groups [8.7 +/- 1.9 kg/m2 (NW), 6.5 +/- 1.9 kg/m2 (EW), and 3.7 +/- 1.4 kg/m2 (LW); P < 0.05, NW vs. EW; P < 0.001, NW vs. LW). Expressed as a percentage of the value in nonwasting HIV-positive controls (NW), the relative loss of fat was greater than the loss of lean mass with progressive degrees of wasting [EW, 25% vs. 6% (fat vs. lean); LW, 58% vs. 13%]. The prevalence of amenorrhea was 20% among study subjects [17% (NW), 10% (EW), and 38% (LW)]. The percent predicted muscle mass was significantly lower in subjects with amenorrhea (74 +/- 8%) compared to that in eumenorrheic HIV-positive subjects (94 +/- 4%; P < 0.05). Estradiol levels were lower among subjects with amenorrhea (17.6 +/- 21.8 pg/mL) compared to eumenorrheic HIV-positive (48.9 +/- 33.6 pg/mL) and control (68.3 +/- 47.6 pg/mL) subjects and did not correlate with body composition. Mean free testosterone, but not total testosterone, levels were decreased in subjects with EW and LW compared to those in age-matched healthy controls, but not compared with those in NW [0.9 +/- 0.6 ng/dL (NW), 0.7 +/- 0.4 ng/dL (EW), 0.6 +/- 0.3 ng/dL (LW), and 2.0 +/- 2.4 ng/dL (controls); P < 0.05, EW vs. controls and LW vs. controls] and correlated with muscle mass (r = 0.37; P < 0.05). The percentages of women with free testosterone levels below the age-adjusted normal range were 33% (NW), 50% (EW), and 66% (LW). Dehydroepiandrosterone sulfate levels were also low in the subjects with LW compared to those in the control group [98 +/- 85 microg/dL (NW), 102 +/- 53 microg/dL (EW), 55 +/- 46 microg/dL (LW), and 132 +/- 68 microg/dL (controls); P < 0.05 LW vs. controls] and were correlated highly with free testosterone levels (r = 0.73; P < 0.00001) and also with muscle mass (r = 0.48; P < 0.01). These data demonstrate that women lose significant lean body and muscle mass in the late stages of wasting. However, in contrast to men, women exhibit a progressive and disproportionate decrease in body fat relative to lean body mass at all stages of wasting, consistent with gender-specific effects in body composition in AIDS wasting. (ABSTRACT TRUNCATED)


Florigen and anti-florigen - a systemic mechanism for coordinating growth and termination in flowering plants.
Genetic studies in Arabidopsis established FLOWERING LOCUS T (FT) as a key flower-promoting gene in photoperiodic systems. Grafting experiments established unequivocal one-to-one relations between SINGLE FLOWER TRUSS (SFT), a tomato homolog of FT, and the hypothetical florigen, in all flowering plants. Additional studies of SFT and SELF PRUNING (SP, homolog of TFL1), two antagonistic genes regulating the architecture of the sympodial shoot system, have suggested that transition to flowering in the day-neutral and perennial tomato is synonymous with "termination." Dosage manipulation of its endogenous and mobile, graft-transmissible levels demonstrated that florigen regulates termination and transition to flowering in an SP-dependent manner and, by the same token, that high florigen levels induce growth arrest and termination in meristems across the tomato shoot system. It was thus proposed that growth balances, and consequently the patterning of the shoot systems in all plants, are mediated by endogenous, meristem-specific dynamic SFT/SP ratios and that shifts to termination by changing SFT/SP ratios are triggered by the imported florigen, the mobile form of SFT. Florigen is a universal plant growth hormone inherently checked by a complementary antagonistic systemic system. Thus, an examination of the endogenous functions of FT-like genes, or of the systemic roles of the mobile florigen in any plant species, that fails to pay careful attention to the balancing antagonistic systems, or to consider its functions in day-neutral or perennial plants, would be incomplete.


How to train your Bayesian: a problem-representation transfer rather than a format-representation shift explains training effects.
People improve their Bayesian reasoning most when they are trained to represent single-event probabilities as natural frequencies; nevertheless, the underlying mechanism of this representational training remains unclear. Several authors suggested that people learn to shift the initial format to natural frequencies, and improve their reasoning because natural frequencies align with an evolutionary designed frequency-coding mechanism--the format-representation shift hypothesis. Alternatively, people may acquire a generic problem representation in terms of nested sets that is then transferred to similar problems--the problem-representation transfer hypothesis. To disentangle the effect of the format shift from problem representation transfer, we devised two types of training with problems featuring a nonfrequency format and a concealed nested-sets structure. Participants learnt the adequate problem representation in both training manipulations, but in only one did they learn, in addition, to shift the format to frequencies. Substantial evidence (BF01 = 5, where BF = Bayes factor) indicates that both types of training improved reasoning in an immediate and a one-week follow-up posttest to the same extent. Such findings support the problem-representation transfer hypothesis because learning an adequate nested-sets problem representation accounts for the performance improvement, whereas the frequency format per se confers no additional benefit. We discuss the implications of these findings for two dominant accounts of statistical reasoning.


[Anatomical study and clinical application of in situ reduction and fixation of anterior medial fenestration approach of femoral head fracture].
Objectives: To explore the feasibility of anterior medial fenestration approach in situ reduction and fixation in the treatment of PipkinⅠ and Ⅱ femoral head fractures,and to explore the clinical effect of this operation. Methods: Hips of two anti-corrosion adult specimens treated with formalin were dissected, then anatomical structures and directional characteristics of anterior medial main muscles,ligaments,blood vessels and nerves were observed.The anterior medial fenestration approach was performed on bilateral hips of four fresh frozen specimens to determine pulling direction of stripped muscles and ligaments required during operation,and to observe and analyze vascular and nerve traction protection directions exposed in the approach.Determine extent of exposure to the approach and assess feasibility of this approach.The clinical data of 12 patients with Pipkin Ⅰ and Ⅱ femoral head fractures who underwent in situ reduction and fixation of anterior medial fenestration at Department of Orthopaedics,Affiliated Hospital of Chengdu University from February 2016 to April 2018 were retrospectively analyzed.There were 3 males and 9 females with an age of 48.5 years(range:37 to 59 years).There were 8 cases of Pipkin type Ⅰ and 4 cases of Pipkin type Ⅱ.The operation time,blood loss,fracture healing time,last Thompson-Epstein evaluation and Harris score were observed. Results: Anterior medial fenestration approach to expose the femoral head in 4 bilateral hips with a total of 8 sides of fresh frozen specimens.The upper boundary of observation fenestration was pubic body (anterior acetabulum),and the outer upper boundary was iliacus and psoas muscle.The lateral boundary is rectus femoris and femoral vessels,the lower boundary was transverse branch of the medial femoral circumflex artery and vein.The medial boundary was pubis muscle,short adductor muscle and long adductor muscle.Pubofemoral and iliofemoral ligament were seen in fenestration. Four quadrants in front of femoral head in fenestration can be seen after cutting switch capsule active hip joint. In 12 patients with femoral head fracture,the operation time was 107.5 minutes(range:90 to 135 minutes),and the intraoperative bleeding volume was 115.0 ml(range:85 to 150 ml).The patients were followed up for 18.6 months(range:12 to 28 months).The fracture healing time of 12 patients was 144.2 days(range:120 to 180 days).The curative effect was evaluated according to Thompson-Epstein standard at the last follow-up:excellent in 6 cases,good in 4 cases and fair in 2 cases.At the last follow-up,the Harris score of hip joints was 85.1(range:75 to 93). Conclusions: Anterior medial fenestration in situ reduction and fixation surgery is feasible for the treatment of Pipkin Ⅰ and Ⅱ femoral head fractures. The short and midterm follow-up reveal satisfactory effect.


Endorphins may function in heat adaptation.
Administration of the opiate antagonist naloxone to rats after acute or chronic heat exposure precipitates an increase in colonic temperature, an increase in escape attempts, and a decrease in body weight. These changes are accompanied by signs associated with hyperthermia such as salivation, diarrhea, and an abnormal extended posture. Although brain endorphin involvement is possible, hypophysectomy diminishes the intensity and magnitude of these naloxone effects, indicating that the naloxone effect in intact animals may be due to a functional antagonism of pituitary endorphins. These observations suggest that endorphins attenuate physiological responses to thermal and noxious stimuli triggered in common neuroanatomical pathways by heat.


Effect of atropine, ouabain, antimycin A, and A23187 on "trigger Ca2+ pool" in exocrine pancreas.
45Ca2+ fluxes have been analyzed in dispersed acinar cells prepared from rat pancreas. Sudden addition of carbamylcholine (CCh) to 45Ca2+-preloaded acinar cells at quasi-steady state for 45Ca2+ resulted in a quick 45Ca2+ release followed by a slower 45Ca2+ reuptake with net accumulation of 45Ca2+. Subsequent sudden addition of atropine caused a further transient increase in cellular 45Ca2+ followed by a slow decrease to a steady-state value. 45Ca2+ release could not be evoked a second time by pancreozymin when prestimulated with CCh. However, if CCh stimulation was abolished by an interposed step of atropine, restimulation by cholecystokinin-pancreozymin was possible. Addition of A23187 or antimycin A to cells induced a fast decrease in cellular 45Ca2+. This effect was not additive to the CCh effect. In ouabain-pretreated cells, the CCh-induced sudden loss of cellular 45Ca2+ was blocked by 60%. The following slow reuptake of 45Ca2+ was blocked completely. Subsequent addition of atropine caused a fast uptake of cellular 45Ca2+ with no secondary decline. The data are consistent with the following model: acetylcholine releases Ca2+ from a cellular "trigger pool" into the cytosol located in or near the cell membrane. Then Ca2+ is extruded from the cell via Ca2+ pumps partly by a Na+-dependent Ca2+ transport system (quick phase of 45Ca2+ release). Subsequently, due to increased Ca2+ permeability of the plasma membrane as induced by acetylcholine, Ca2+ influx occurs and Ca2+ is taken up from the cytosol into intracellular Ca2+ pools (slow 45Ca2+ reuptake phase). Atropine causes refilling of the trigger Ca2+ pool and return of the increased Ca2+ permeability of the plasma membrane back to the unstimulated state.


Asymmetric construction of quaternary centers by enantioselective allylation: application to the synthesis of the serotonin antagonist LY426965.
[reaction: see text] Catalytic enantioselective allylation with a chiral bisphosphoramide was applied to the synthesis of LY426965, a serotonin antagonist. The key step, addition of a 3,3-disubstituted allyltrichlorosilane to benzaldehyde, provided the adduct containing a stereogenic quaternary center with excellent diastereoselectivity and enantioselectivity.


MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma.
Patients with primary sclerosing cholangitis (PSC) are at high risk for the development of cholangiocarcinoma (CC). Analysis of micro ribonucleic acid (MiRNA) patterns is an evolving research field in biliary pathophysiology with potential value in diagnosis and therapy. Our aim was to evaluate miRNA patterns in serum and bile of patients with PSC and/or CC. Serum and bile from consecutive patients with PSC (n = 40 (serum), n = 52 (bile)), CC (n = 31 (serum), n = 19 (bile)) and patients with CC complicating PSC (PSC/CC) (n = 12 (bile)) were analyzed in a cross-sectional study between 2009 and 2012. As additional control serum samples from healthy individuals were analyzed (n = 12). The miRNA levels in serum and bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation. Serum analysis revealed significant differences for miR-1281 (p = 0.001), miR-126 (p = 0.001), miR-26a (p = 0.001), miR-30b (p = 0.001) and miR-122 (p = 0.034) between patients with PSC and patients with CC. All validated miRNAs were significantly lower in healthy individuals. MiR-412 (p = 0.001), miR-640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) were significantly different between patients with PSC and PSC/CC in bile. Patients with PSC and/or CC have distinct miRNA profiles in serum and bile. Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.


Coevolutionary constraints in the sequence-space of macromolecular complexes reflect their self-assembly pathways.
Is the order in which biomolecular subunits self-assemble into functional macromolecular complexes imprinted in their sequence-space? Here, we demonstrate that the temporal order of macromolecular complex self-assembly can be efficiently captured using the landscape of residue-level coevolutionary constraints. This predictive power of coevolutionary constraints is irrespective of the structural, functional, and phylogenetic classification of the complex and of the stoichiometry and quaternary arrangement of the constituent monomers. Combining this result with a number of structural attributes estimated from the crystal structure data, we find indications that stronger coevolutionary constraints at interfaces formed early in the assembly hierarchy probably promotes coordinated fixation of mutations that leads to high-affinity binding with higher surface area, increased surface complementarity and elevated number of molecular contacts, compared to those that form late in the assembly. Proteins 2017; 85:1183-1189. © 2017 Wiley Periodicals, Inc.


Test of leukocyte migration inhibition. 1. Value of the test in the diagnosis of certain immune diseases.
The test of leukocyte migration inhibition (LMI) being a specific and sensitive method for the detection of cell-mediated immunity, its ever increasing use in the clinic necessitates a more accurate estimation of its actual value. The technique used in this study is that of leukocyte migration in capillary tubes according to Soborg and Bendixen. The test was performed in three groups of patients: A--with drug intoxication; B--with chronic post viral hepatitis and C--with alcoholic liver disease. The results obtained showed that in the patients with drug allergy the LMI test using the incriminated drugs as antigens was positive in 83% of the cases, in the patients with chronic post viral hepatitis the cellular migration inhibition to the HBsAg was observed in 35% of the cases and in alcoholic liver disease lymphocyte sensitization to ethanol was present in 28.7% of the cases. It is concluded that in drug allergy the LMI test is useful and has diagnostic value being preferable to other in vitro determinations and even, in certain cases, to the skin tests. In chronic liver diseases the value of the test is limited to investigation purposes as it can reveal the degree of involvement of cell-mediated immunity in the pathogenesis of disease.


Recurrent syndrome of inappropriate antidiuretic hormone secretion due to tolterodine in an elderly male patient.
Hyponatremia is defined as serum sodium of <135 mmol/L and equates with a low serum osmolality once translocational hyponatremia and pseudohyponatremia are ruled out. True hyponatremia develops when normal urine-diluting mechanisms are disturbed. In elderly patients, this complication is not uncommon, especially in nursing homes and assisted living facilities. Medications are often the most common cause of hyponatremia in these patients. Herewith, we reported a 65-year-old Saudi male, a known case of benign prostatic hypertrophy and hypertension, who developed recurrent hyponatremia secondary to tolterodine. To our knowledge, this is the fifth case reported in literature of such association.


Mechanism of exotic density-wave and beyond-Migdal unconventional superconductivity in kagome metal AV3Sb5 (A = K, Rb, Cs).
Exotic quantum phase transitions in metals, such as the electronic nematic state, have been discovered one after another and found to be universal now. The emergence of unconventional density-wave (DW) order in frustrated kagome metal AV3Sb5 and its interplay with exotic superconductivity attract increasing attention. We find that the DW in kagome metal is the bond order, because the sizable intersite attraction is caused by the quantum interference among paramagnons. This mechanism is important in kagome metals because the geometrical frustration prohibits the freezing of paramagnons. In addition, we uncover that moderate bond-order fluctuations mediate sizable pairing glue, and this mechanism gives rise to both singlet s-wave and triplet p-wave superconductivity. Furthermore, characteristic pressure-induced phase transitions in CsV3Cb5 are naturally understood by the present theory. Thus, both the exotic density wave and the superconductivity in geometrically frustrated kagome metals are explained by the quantum interference mechanism.


Fasting-induced depletion of glutathione in the aging mouse.
Previous results indicate that aging is associated with a general deficiency of glutathione (GSH). As fasting is also known to lower hepatic GSH levels, we investigated the combined effects of aging and 24 hr of food deprivation on liver, kidney and blood GSH and cyst(e)ine levels in C57BL/6N mice of ages 6 (young), 12 (mature) and 24 (old) months. No age-related differences in baseline hepatic GSH were observed in these mice, consistent with previous findings where the deficiency in liver is not apparent until about 29 months of age. By 6 hr of fasting, an age-related reduction in hepatic GSH was evident, culminating in a 4-fold greater decrease during maturation, and a 5-fold greater decrease during aging (P < 0.001) compared to young animals. Liver weight also declined, decreasing total liver GSH content by 24% in young, 44% in mature, and 56% in old mice. Renal GSH and hepatic cyst(e)ine concentrations were unaffected by fasting. In young and mature mice, depletion of hepatic GSH was accompanied by a concomitant increase in blood GSH and kidney cyst(e)ine levels after 6 hr of fasting, suggesting enhancement of hepatic GSH efflux. However, in old animals, GSH depletion was associated with decreased blood GSH and kidney cyst(e)ine. Altogether, these results suggest that the stress of fasting reveals aging changes in hepatic GSH homeostasis occurring well before the GSH deficiency of aging is observed. These aging changes are likely due to decreased GSH turnover resulting from impaired biosynthesis.


Efficient delivery of streptavidin to mammalian cells: clathrin-mediated endocytosis regulated by a synthetic ligand.
The efficient delivery of macromolecules to living cells presents a formidable challenge to the development of effective macromolecular therapeutics and cellular probes. We describe herein a novel synthetic ligand termed "Streptaphage" that enables efficient cellular uptake of the bacterial protein streptavidin by promoting noncovalent interactions with cholesterol and sphingolipid-rich lipid raft subdomains of cellular plasma membranes. The Streptaphage ligand comprises an N-alkyl derivative of 3 beta-cholesterylamine linked to the carboxylate of biotin through an 11-atom tether. Molecular recognition between streptavidin and this membrane-bound ligand promotes clathrin-mediated endocytosis, which renders streptavidin partially intracellular within 10 min and completely internalized within 4 h of protein addition. Analysis of protein uptake in Jurkat lymphocytes by epifluorescence microscopy and flow cytometry revealed intracellular fluorescence enhancements of over 300-fold (10 microM ligand) with >99% efficiency and low toxicity. Other mammalian cell lines including THP-1 macrophages, MCF-7 breast cancer cells, and CHO cells were similarly affected. Structurally related ligands bearing a shorter linker or substituting the protonated steroidal amine with an isosteric amide were ineffective molecular transporters. Confocal fluorescence microscopy revealed that Streptaphage-induced uptake of streptavidin functionally mimics the initial cellular penetration steps of Cholera toxin, which undergoes clathrin-mediated endocytosis upon binding to the lipid raft-associated natural product ganglioside GM1. The synthetic ligand described herein represents a designed cell surface receptor capable of targeting streptavidin conjugates into diverse mammalian cells by hijacking the molecular machinery used to organize cellular membranes. This technology has potential applications in DNA delivery, tumor therapy, and stimulation of immune responses.


Surgical resection of tumors located in subcortex of language area.
Although functional mapping facilitates the planning of surgery in and around eloquent areas, the resection of tumors adjacent to language areas remains challenging. In this report, we took notice that the language areas (Broca's and Wernicke's) present at the perisylvian fissure. We posit that if there is non-essential language area on the inner surface of the Sylvian fissure, safe tumor resection may be possible even if the tumor is located under the language cortex. The study population consisted of 5 patients with intrinsic brain tumors (frontal glioma, n = 3; temporal cavernous angioma, n = 1; primary malignant central nervous system lymphoma, n = 1) located in the perisylvian subcortex, in the language-dominant hemisphere. All patients underwent awake surgery and we performed intra-operative bipolar cortical functional language mapping. When the tumor was located under the language area, the Sylvian fissure was opened and the inner surface of the opercular cortex was exposed with the patient asleep, and additional functional mapping of that cortex was performed. This enabled us to remove the tumor from the non-functioning cortex. In our series, 4 of 5 patients had not language function on the inner surface of the operculum. Only one patient, a 52-year-old man with frontal glioblastoma (Case 3) had language function on the inner surface of the frontal operculum. We suggest that even perisylvian tumors located in the subcortex of the language area may be resectable via the nonfunctioning intrasylvian cortex by a transopercular approach without resultant language dysfunction.


Bacterial expression of a single-chain Fv fragment which efficiently protects the acetylcholine receptor against antigenic modulation caused by myasthenic antibodies.
Monoclonal antibodies (mAb) against the main immunogenic region (MIR) of the acetylcholine receptor (AChR) are very potent in inducing antigenic modulation of the AChR in animals and in muscle cell cultures. A recombinant antibody fragment of the rat anti-MIR mAb198 was cloned by polymerase chain reaction and expressed as soluble single-chain Fv fragment (scFv198) in E. coli and affinity purified. DNA sequencing was used to define the VH (IB) and VL (K2) chain gene usage. scFv198 was found immunologically and biologically active. Its binding affinity for the Torpedo AChR (KD = 2 +/- 0.6 nM) was very similar with that of the intact mAb198 (KD = 1.8 +/- 0.6 nM) while for the human AChR (KD = 80.7 +/- 16.6 nM) it was about four times lower than that of the intact mAb198 (KD = 21.6 +/- 6.6 nM). This fragment was capable of efficiently protecting the AChR in human cell cultures, against antigenic modulation caused by the intact mAb198 or by the antibodies from a myasthenic patient. The produced scFv198 fragment is, therefore, potentially useful in therapeutic applications for myasthenia gravis after appropriate genetic manipulations.


Recent advances in understanding and managing body dysmorphic disorder.
Body dysmorphic disorder (BDD) is a relatively common and disabling psychiatric disorder characterised by excessive and persistent preoccupation with perceived defects or flaws in one's appearance, which are unnoticeable to others, and associated repetitive behaviours (eg, mirror checking). The disorder generally starts in adolescence, but often goes unnoticed and is severely underdiagnosed. Left untreated, BDD typically persists and causes marked functional impairment in multiple domains. This clinical review considers recent advances in the epidemiology and classification of BDD, including its reclassification in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders under the new 'Obsessive-Compulsive and Related Disorders' chapter. Key issues in assessment are outlined including the use of validated screening instruments to minimise misdiagnosis and the importance of risk assessment in this population given the high rates of suicidality and inappropriate use of cosmetic treatments. In addition, current knowledge regarding the causes and mechanisms underlying BDD are summarised. The recommended treatments for BDD are outlined, namely cognitive behavioural therapy (CBT) and antidepressants, such as selective serotonin reuptake inhibitors. Both CBT and pharmacotherapy have been shown to be efficacious treatments for BDD in adult populations, and evidence is emerging to support their use in young people. Although the majority of patients improve with existing evidence-based treatment, a large proportion are left with clinically significant residual symptoms. Priorities for future research are therefore discussed including the need to further refine and evaluate existing interventions with the goal of improving treatment outcomes and to increase their availability.


A new microbial gluten-degrading prolyl endopeptidase: Potential application in celiac disease to reduce gluten immunogenic peptides.
Gluten is a complex of proteins present in barley, wheat, rye and several varieties of oats that triggers celiac disease in genetically predisposed subjects. Gluten is notoriously difficult to digest by mammalian proteolytic enzymes and therefore, proline-rich digestion-resistant peptides contain multiple immunogenic epitopes. Prolyl endopeptidases (PEP) hydrolyse internal proline residues on the carboxyl side of peptides and have been proposed for food gluten detoxification and as oral enzyme supplementation for celiacs. The aim of this study was to identify new gluten-degrading microbial enzymes with the potential to reduce gluten immunogenicity by neutralizing its antigenic epitopes. Using a gluten-degrading colony screening approach, a bacterial isolate (2RA3) displaying the highest glutenase activity was selected, characterized and its genome completely sequenced. The identification through 16S rDNA gene sequencing showed a 99,1% similarity to Chryseobacterium taeanense. Hydrolysis of gluten immunogenic peptides (GIP) was further monitored, over a 48-hour period, by colony encapsulation in gliadin-containing microspheres, followed by detection with the G12 anti-GIP monoclonal antibody. Glutenase activity was detected in the extracellular medium of 2RA3 cultures, where gel electrophoresis and gliadin zymography revealed the presence of a ~50 kDa gluten-degrading enzyme. Nano-ESI-Q-TOF of the excised active band identified 7 peptides contained in the protein product predicted for an open reading frame (ORF) in the 2RA3 genome. Based on sequence similarity to the PEP family, the new enzyme was named PEP 2RA3. The PEP 2RA3 coding sequence was PCR-amplified from C. taeanense 2RA3, cloned and expressed in Escherichia coli as a C-terminally His-tagged recombinant protein and purified by Ni-NTA affinity chromatography. The recombinant protein, with predicted molecular mass and isoelectric point of 78.95 kDa and 6.8, respectively, shows PEP activity with standard chromogenic substrates, works optimally at pH 8.0 and 30°C and remains stable at pH 6.0 and 50°C, indicating a potential use in gluten-containing food process applications. The ability of the recombinant enzyme to degrade GIP in beer into smaller peptides was confirmed.


A mechanistic model of COR15 protein function in plant freezing tolerance: integration of structural and functional characteristics.
Plants as sessile organisms are strongly challenged by environmental stresses. Many plants species are able to cold-acclimate, acquiring higher freezing tolerance upon exposure to low but non-freezing temperatures. Among a plethora of adaptational processes, this involves the accumulation of cold regulated (COR) proteins that are assumed to stabilize and protect cellular structures during freezing. However, their molecular functions are largely unknown. We recently reported a comprehensive study of 2 intrinsically disordered cold regulated chloroplast proteins, COR15A and COR15B from Arabidopsis thaliana. They are necessary for full cold acclimation. During freezing, they stabilize leaf cells through folding and binding to chloroplast membranes. Contrary to evidence from in-vitro experiments, they play no role in enzyme stabilization in vivo. Elucidating these major functional and structural characteristics and estimation of protein abundance allow us to propose a detailed model for the mode of action of the two COR15 proteins.


Research Progress of Ferroptosis: A Bibliometrics and Visual Analysis Study.
Ferroptosis is a type of cell death with major topic of debate under current research and plays an important role in disease regulation. In this study, the literature management software Bibexcel and knowledge graph tool VOSviewer were used to summarize and analyze the international research trends and hotspots about ferroptosis in recent years, which highlight the disease mechanism, diagnosis, and treatment related to ferroptosis. Material/Methods. The core collection database of Web of Science was used for retrieving ferroptosis research literature. The information such as the amount of text, the country, the period, the institution, the fund, and the keywords was extracted by the bibliometric tool Bibexcel. The cooccurrence and clustering function of VOSviewer were used to analyze the high-frequency keywords and the cooperative network of the author, institution, and country. The research of ferroptosis started late and was formally proposed in 2012. It has developed rapidly and presented an "exponential" growth trend. China, the United States, Germany, Japan, and France are the main national forces of ferroptosis research development. The United States and China have a relatively high degree of support and attention to ferroptosis. Exploring oxidative stress, inducers/inhibitors, synergistic antitumor effect, relationships with other cell death types, GSH/GPX4 and iron metabolism imbalance related mechanisms of ferroptosis, and ferroptosis in the nervous system disease, ischemia-reperfusion injury, tumor, inflammation, and age-related diseases are the hot research directions. Ferroptosis has been a research hotspot in the field of biomedicine in recent years and has attracted the attention of scholars all over the world. The occurrence mechanism of ferroptosis and its application in neurological diseases, ischemia and reperfusion injury, tumors, inflammation, and aging are the hot directions of current research. In the future, ferroptosis can be appropriately considered for strengthening new approaches, new diseases, new inductors, new inhibitors, clinical transformation, and traditional medicine research.


Simultaneous fitting of X-ray and neutron diffuse scattering data.
Conventional crystallographic refinement uses the Bragg-peak intensities and gives the single-site average crystal structure. Information about short-range order and local order is contained in the diffuse scattering that is distributed throughout reciprocal space. Models of the short-range order in materials can now be automatically refined. The complementarity of X-ray and neutron diffraction data, and the value of simultaneously refining a structural model against both types of data, has long been known. This paper presents the first refinement of a short-range-order model against comprehensive X-ray and neutron diffuse scattering data simultaneously. The sample is the organic molecular crystal benzil, C(14)H(10)O(2) (for neutron work H is replaced by D). The technique gives new insights into local order in crystalline materials, including the dynamic correlation structure indicative of the dynamics of molecules in the crystalline state, and successfully overcomes limitations of using only the X-ray data set.


Outcomes of adding acute care nurse practitioners to a Level I trauma service with the goal of decreased length of stay and improved physician and nursing satisfaction.
The trauma service experienced preventable delays caused by an Accreditation Council for Graduate Medical Education work restrictions and a 16% increase in patient census. Furthermore, nurses needed a consistently accessible provider for the coordination of care. We hypothesized that using experienced acute care nurse practitioners (ACNPs) on the stepdown unit would improve throughput and decrease length of stay (LOS) and hospital charges. Moreover, we hypothesized that adding ACNPs would improve staff satisfaction. On December 1, 2011, the Vanderbilt University Medical Center Division of Trauma reassigned ACNPs to the stepdown area 5 days a week for a pilot program. LOS data from December 1, 2011 through December 1, 2012 was compared with data from the same months from the previous two years and estimated hospital charges and patient days were extrapolated. Physician and nursing surveys were performed. Data from 2010 (n = 2,559) and 2011 (n= 2,671) were averaged and the mean LOS for the entire trauma service was 7.2 days. After adding an experienced ACNP, the average LOS decreased to 6.4 days, a 0.8 day reduction. Per patient, there was a $ 9,111.50 savings in hospital charges, for a reduction of $27.8 million dollars in hospital charges over the 12 month pilot program. A confidential survey administered to attending physicians showed that 100% agreed that a nurse practitioner in the stepdown area was beneficial and helped throughput. Dayshift nurses were surveyed, and 100% agreed or strongly agreed that the ACNPs were knowledgeable about the patient's plan of care, experienced in the care of trauma patients, and improved patient care overall. The addition of experienced ACNPs resulted in the decrease of overall trauma service LOS, saving almost $9 million in hospital charges. Economic/decision study, level III.


Prioritising drug and therapeutics committee (DTC) decisions: a national survey.
A national survey was conducted to explore stakeholder opinions about: (1) the domains of activity and criteria used to determine "important" decisions; (2) the "importance" of Drug and Therapeutics Committee (DTC) decisions as an appropriate approach for prioritising implementation and actions and (3) how DTC decisions could be prioritised for action. This is a study of DTCs conducted in the Australian health care setting. A semi-structured questionnaire was sent to Directors of Pharmacies or Chief Pharmacists in Australian hospitals. Questionnaires could be returned by email or by fax. Two weeks after initial mail-out, non-responders were followed-up. Responses were collated and analysed using descriptive statistics. Free-text responses were collated. QSR NVivo was used as a data management tool. The response rate was 61%. All respondents indicated that "patient safety" was a domain of importance for a decision. Other domains of important DTC decisions include: "ensuring the practice of evidence based medicine within their institution" (94%), "cost" (93%), "ensure practice according to legislative requirements" (87%). Most respondents agreed that some DTC decisions were more important than others. Given constraints on time and resources, the majority agreed that DTC decisions should be prioritised for implementation, although most had no suggestions about how this could be done. Some suggested that the domains of importance could be the basis for priority assignment. Currently DTC decisions and policies are implemented in an ad hoc manner. As a result implementation may be incomplete and ineffective, and may pose a risk of serious consequences in patient care. This study identifies the domains or criteria of DTC decisions so that DTCs may allocate scarce resources to the systematic implementation of important decisions.


Impacted gutkha presenting as an intrabronchial mass lesion leading to post-obstructive pneumonia.
A 66-year-old man presented with a chief complaint of difficulty breathing and productive cough. CT scan of the chest revealed an endobronchial mass with associated "tree-in-bud" opacities. A bronchoscopic biopsy of the mass was performed due to clinical suspicion of malignancy. Microscopic examination revealed inflamed endobronchial mucosa, granulation tissue and abundant fragments of uncharacterized organic material, compatible with aspiration. Detailed history revealed a history of chewing "gutkha", a form of smokeless tobacco comprising a mixture of betel nut and other condiments. Microscopic sections of a betel nut and the "gutkha mix" processed subsequently in the histology laboratory were found to be similar to the organic material found in the mass. Thus, a diagnosis of impacted betel nut mixture leading to post-obstructive pneumonia was rendered.


Preliminary evaluation of a fuzzy logic-based automatic quantitative analysis in myocardial SPECT.
This study validates a new quantitative myocardial perfusion SPECT software. The processing starts with the extraction of the morphologic skeleton of the left ventricular myocardium from reconstructed transverse sections. Fuzzy logic is used to decide whether a pixel belongs to the myocardium and any perfusion defect is filled according to a truncated bullet model. The resulting image is partitioned in 18 isovolumetric sectors. Sex-matched normal limits, criteria of abnormality for rest (201)Tl and (99m)Tc-labeled perfusion tracers, reproducibility studies, and detection of coronary artery disease were developed and validated in an overall population of 343 patients. The sex- and tracer-matched means and SDs of a normal response were calculated in 93 male and 93 female patients with a <5% likelihood of coronary artery disease. Reproducibility measurements and assignment of different sectors of the myocardium to a specific coronary were performed from data collected in 49 and 60 patients, respectively. The accuracy of the detection of a coronary artery occlusion was assessed in 48 patients who also underwent coronary angiography. The intra- and interoperator reproducibility of the sectorial activity was high with a linear regression coefficient of 0.97 and a SD of the difference measurement at 4.4% and 3.8%, respectively. Overall sensitivity and specificity for the detection of occluded coronary artery were 90% and 80%, respectively. For the detection of left anterior descending, left circumflex, and right artery coronary occlusion, sensitivity was 92%, 75%, and 92.5%, respectively, and specificity was 75%, 78%, and 90%, respectively. The new quantitative myocardial perfusion SPECT software appears to be a very helpful program for the objective analysis of perfusion tracer distribution in myocardial SPECT and a very accurate tool in the detection and localization of coronary artery occlusion.


Quantum Smoluchowski equation: a systematic study.
The strong-friction regime at low temperatures is analyzed systematically starting from the formally exact path-integral expression for the reduced dynamics. This quantum Smoluchowski regime allows for a type of semiclassical treatment in the inverse friction strength so that higher-order quantum corrections to the original quantum Smoluchowski equation [J. Ankerhold, P. Pechukas, and H. Grabert, Phys. Rev. Lett. 87, 086802 (2001); J. Ankerhold and H. Grabert, Phys. Rev. Lett. 101, 119903 (2008)] can be derived. Drift and diffusion coefficients are determined by the equilibrium distribution in position and are directly related to the corresponding action of extremal paths and fluctuations around them. It is shown that the inclusion of higher-order corrections reproduces the quantum enhancement above crossover for the decay rate out of a metastable well exactly.


Trifocal intraocular lenses versus bifocal intraocular lenses after cataract extraction among participants with presbyopia.
Presbyopia occurs when the lens of the eyes loses its elasticity leading to loss of accommodation. The lens may also progress to develop cataract, affecting visual acuity and contrast sensitivity. One option of care for individuals with presbyopia and cataract is the use of multifocal or extended depth of focus intraocular lens (IOL) after cataract surgery. Although trifocal and bifocal IOLs are designed to restore three and two focal points respectively, trifocal lens may be preferable because it restores near, intermediate, and far vision, and may also provide a greater range of useful vision and allow for greater spectacle independence in individuals with presbyopia. To assess the effectiveness and safety of implantation with trifocal versus bifocal IOLs during cataract surgery among participants with presbyopia. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 9); Ovid MEDLINE; Embase.com; PubMed; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 26 September 2019. We searched the reference lists of the retrieved articles and the abstracts from the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) for the years 2005 to 2015. We included randomized controlled trials that compared trifocal and bifocal IOLs among participants 30 years or older with presbyopia undergoing cataract surgery. We used standard Cochrane methodology. We identified five studies conducted in Europe with a total of 175 participants. All five studies assessed uncorrected distance visual acuity (primary outcome of the review), while some also examined our secondary outcomes including uncorrected near, intermediate, and best-corrected distance visual acuity, as well as contrast sensitivity. Study characteristics All participants had bilateral cataracts with no pre-existing ocular pathologies or ocular surgery. Participants' mean age ranged from 58 to 64 years. Only one study reported on gender of participants, and they were mostly women. We assessed all the included studies as being at unclear risk of bias for most domains. Two studies received financial support from manufacturers of lenses evaluated in this review, and at least one author of another study reported receiving payments for delivering lectures with lens manufacturers. Findings All studies compared trifocal versus bifocal IOL implantation on visual acuity outcomes measured on a LogMAR scale. At one year, trifocal IOL showed no evidence of effect on uncorrected distance visual acuity (mean difference (MD) 0.00, 95% confidence interval (CI) -0.04 to 0.04; I2 = 0%; 2 studies, 107 participants; low-certainty evidence) and uncorrected near visual acuity (MD 0.01, 95% CI -0.04 to 0.06; I2 = 0%; 2 studies, 107 participants; low-certainty evidence). Trifocal IOL implantation may improve uncorrected intermediate visual acuity at one year (MD -0.16, 95% CI -0.22 to -0.10; I2= 0%; 2 studies, 107 participants; low-certainty evidence), but showed no evidence of effect on best-corrected distance visual acuity at one year (MD 0.00, 95% CI -0.03 to 0.04; I2= 0%; 2 studies, 107 participants; low-certainty evidence). No study reported on contrast sensitivity or quality of life at one-year follow-up. Data from one study at three months suggest that contrast sensitivity did not differ between groups under photopic conditions, but may be worse in the trifocal group in one of the four frequencies under mesopic conditions (MD -0.19, 95% CI -0.33 to -0.05; 1 study; I2 = 0%, 25 participants; low-certainty evidence). In two studies, the investigators observed that participants' satisfaction or spectacle independence may be higher in the trifocal group at six months, although another study found no evidence of a difference in participant satisfaction or spectacle independence between groups. Adverse events Adverse events reporting varied among studies. Two studies reported information on adverse events at one year. One study reported that participants showed no intraoperative or postoperative complications, while the other study reported that four eyes (11.4%) in the bifocal and three eyes (7.5%) in the trifocal group developed significant posterior capsular opacification requiring YAG capsulotomy. The certainty of the evidence was low. There is low-certainty of evidence that compared to bifocal IOL, implantation of trifocal IOL may improve uncorrected intermediate visual acuity at one year. However, there is no evidence of a difference between trifocal and bifocal IOL for uncorrected distance visual acuity, uncorrected near visual acuity, and best-corrected visual acuity at one year. Future research should include the comparison of both trifocal IOL and specific bifocal IOLs that correct intermediate visual acuity to evaluate important outcomes such as contrast sensitivity and quality of life.


Morphological characteristics of conjunctival squamous papillomas in relation to human papillomavirus infection.
To determine the prevalence of a broad spectrum of human papillomavirus (HPV) types in conjunctival papillomas and a possible difference in clinical and histopathological presentation of HPV-positive and HPV-negative papillomas. Formalin-fixed, paraffin-embedded papilloma tissue specimens obtained from 25 patients were analysed using six different PCR-based methods targeting 87 HPV types from four different papillomavirus (PV) genera: α-PV, β-PV, γ-PV and µ-PV, and in situ hybridisation for HPV-6/HPV-11. Slides were reviewed for pedunculated or sessile growth, the presence of goblet cells, keratinising or non-keratinising epithelium, elastosis, atypia and koilocytes. α-PV types HPV-6 and HPV-11 were detected in 19/25 (76%) conjunctival papilloma tissue specimens, 9 (47%) of which were also HPV-6/HPV-11 positive with in situ hybridisation. Six different β-PV types-HPV-9, HPV-12, HPV-20, HPV-21, HPV-22, HPV-24-were additionally detected in four cases, all of which were also HPV-6/HPV-11 positive. No γ-PVs or µ-PVs were found in any of the tested tissues samples. Extralimbal location (p=0.021), presence of goblet cells (p=0.005), non-keratinising squamous epithelium (p=0.005), and absence of elastosis (p=0.005) were associated with the presence of HPV-6/HPV-11. We demonstrated that certain clinical and histological features are more frequently associated with HPV infection and that HPV genera other than α-PV are most probably not significant factors in conjunctival papilloma occurrence.


Trichinellosis during pregnancy: a case control study in the Lao Peoples' Democratic Republic.
Transmission of Trichinella to humans is still a global public health concern. Although theoretically possible, vertical transmission of Trichinella has rarely been investigated. In June 2005 an outbreak of trichinellosis was reported in Udomxay province, the Northern Lao Peoples' Democratic Republic (PDR). In February and March 2006 we performed a study of all pregnant and lactating mothers and infants in the location of this outbreak to assess the possible occurrence of vertical transmission. The study used questionnaires, mother and child clinical examinations, and serology (Western blot) and, based on the results, women were classified as suspect, possible, or confirmed cases. A control group included unexposed pregnant women and their children. Among 200 women from 21 villages, 8 were confirmed positive for trichinellosis by serology; 4 of these were symptomatic. Among their children, one died in utero at 26 weeks gestation due to maternal hepatitis of unknown etiology and a second child had Trichinella-specific IgG antibodies but was clinically normal. A third child, with negative serology had an inter-ventricular cardiac communication. The remaining children did not differ from controls. Our results cannot prove that transmission of trichinellosis occurs from mother to child.


Sustained Sub-60 mV/decade Switching via the Negative Capacitance Effect in MoS2 Transistors.
It has been shown that a ferroelectric material integrated into the gate stack of a transistor can create an effective negative capacitance (NC) that allows the device to overcome "Boltzmann tyranny". While this switching below the thermal limit has been observed with Si-based NC field-effect transistors (NC-FETs), the adaptation to 2D materials would enable a device that is scalable in operating voltage as well as size. In this work, we demonstrate sustained sub-60 mV/dec switching, with a minimum subthreshold swing (SS) of 6.07 mV/dec (average of 8.03 mV/dec over 4 orders of magnitude in drain current), by incorporating hafnium zirconium oxide (HfZrO2 or HZO) ferroelectric into the gate stack of a MoS2 2D-FET. By first fabricating and characterizing metal-ferroelectric-metal capacitors, the MoS2 is able to be transferred directly on top and characterized with both a standard and a negative capacitance gate stack. The 2D NC-FET exhibited marked enhancement in low-voltage switching behavior compared to the 2D-FET on the same MoS2 channel, reducing the SS by 2 orders of magnitude. A maximum internal voltage gain of ∼28× was realized with ∼12 nm thick HZO. Several unique dependencies were observed, including threshold voltage (Vth) shifts in the 2D NC-FET (compared to the 2D-FET) that correlate with source/drain overlap capacitance and changes in HZO (ferroelectric) and HfO2 (dielectric) thicknesses. Remarkable sub-60 mV/dec switching was obtained from 2D NC-FETs of various sizes and gate stack thicknesses, demonstrating great potential for enabling size- and voltage-scalable transistors.


Cognitive-behavioral group therapy for patients with irritable bowel syndrome.
This article is divided into two parts, the first of which focuses on a general overview of irritable bowel syndrome (IBS) and provides a rationale for the use of cognitive-behavioral therapy (CBT) for IBS based on both theoretical and research perspectives. This section includes a critical review of CBT therapies for IBS and provides a model of CBT for IBS. The second section provides the clinician with practical information concerning the application of cognitive-behavioral group therapy for IBS. Possible scripts and case examples are incorporated into this section to highlight factors that may arise in working with IBS patients relative to other clinical groups. The second section also contains themes that are suggested content areas for group sessions. Contingent on the formulation of the presenting or emerging issues and goals, the order and inclusion of themes can be changed to fit the particular needs of a given group. Finally, this section provides initial preliminary data from a randomized controlled study that is suggestive of the efficacy of cognitive-behavioral therapy for IBS.