Early life events, sex, and arterial blood pressure in critically ill infants.
To determine whether photo-protecting total parenteral nutrition in preterm infants influences arterial blood pressure differently according to gender. Blood pressure is influenced by complex mechanisms of vasomodulation. Oxidants are mediators and effectors in such reactions. Shielding total parenteral nutrition from light contributes to decrease the generation of peroxides. Girls may be better protected against an oxidant load than boys. We questioned whether shielding total parenteral nutrition may have cardiovascular effects that are influenced by gender. A post hoc subgroup analysis of the effect of shielding parenteral nutrition from light. Neonatal intensive care unit. Preterm infants <1000 g with indwelling arterial catheters who received light exposed (n = 20) or light protected (n = 20) parenteral nutrition. Invasive monitoring, total parenteral nutrition. Arterial blood pressure was recorded hourly and compared between light exposed and light protected over the first week of life; timed average maximum velocity (m/s) was measured in the superior mesenteric artery by Doppler; presence of ductus arteriosus was documented by cardiac ultrasound. Data were analyzed by analysis of variance. No differences were noted between light exposed and light protected in clinical determinants that may influence blood pressure. There was an interaction (p < .01) between gender and total parenteral nutrition on blood pressure. In girls (n = 17), systolic and diastolic blood pressures were higher (p < .01) and heart rate lower (p < .01) during light exposed. There was no effect on BP observed in boys (n = 23). The linear correlation between timed average maximum velocity and systolic blood pressure was positive (p < .05). There was no echocardographic difference in hemodynamic variables between boys (n = 21) and girls (n = 9) who had a patent ductus. Failure to shield total parenteral nutrition from light results in higher blood pressure in a selected population of critically ill female infants. This information adds to our understanding of the multiple determinants involved in optimizing arterial blood pressure in a critical care environment.


Mixture-modelling-based Bayesian MH-RM algorithm for the multidimensional 4PLM.
Several recent works have tackled the estimation issue for the unidimensional four-parameter logistic model (4PLM). Despite these efforts, the issue remains a challenge for the multidimensional 4PLM (M4PLM). Fu et al. (2021) proposed a Gibbs sampler for the M4PLM, but it is time-consuming. In this paper, a mixture-modelling-based Bayesian MH-RM (MM-MH-RM) algorithm is proposed for the M4PLM to obtain the maximum a posteriori (MAP) estimates. In a comparison of the MM-MH-RM algorithm to the original MH-RM algorithm, two simulation studies and an empirical example demonstrated that the MM-MH-RM algorithm possessed the benefits of the mixture-modelling approach and could produce more robust estimates with guaranteed convergence rates and fast computation. The MATLAB codes for the MM-MH-RM algorithm are available in the online appendix.


Health Behavior Differences Between Male and Female U.S. Military Personnel by Sexual Orientation: The Importance of Disaggregating Lesbian, Gay, and Bisexual Groups.
The aims of the study are to identify health-related behaviors associated with sexual orientation among active duty military personnel and to compare those behaviors when lesbian, gay, and bisexual (LGB) groups are aggregated and disaggregated. We used public data from the 2015 Health-Related Behavior Survey of Active Duty Military Personnel. Binomial logistic regression analyses were used to examine differences between and within heterosexual, same-sex, and bisexual groups as predicted by the following correlates: demographic characteristics, physical activity, substance use, probable mood disorders, unwanted sexual contact, physical abuse, suicidal behaviors, and sexually transmitted infection (STI). In univariate analyses, rates of lifetime unwanted sexual contact and lifetime suicidal ideation were significantly higher for bisexual females compared to other groups. The results of regression analyses differed depending on whether LGB groups were aggregated or disaggregated. Aggregated LGB versus heterosexual model found significant differences with respect to unwanted sexual contact, lifetime suicide attempt, STI, smoking, and marijuana use. Disaggregated models found different patterns of significant correlates, e.g., correlates comparing gays to heterosexual males were STI, sexual contact, lifetime suicide attempt, and age; correlates comparing lesbians to heterosexual females were heavy drinking, probable post-traumatic stress disorder, ever used marijuana, lifetime suicide attempt, lifetime physical abuse, and smoking. The findings are consistent with those of previous research showing highest risk for suicidal behaviors and substance abuse among bisexual individuals. We recommend that future studies and clinical care consider LGB sexual identities as heterogeneous groups; otherwise, risks for adverse health behaviors may be overlooked.


Solubility and stability enhancement of atorvastatin by cyclodextrin complexation.
The objective of the study was to increase the solubility, stability, and dissolution rate of atorvastatin calcium (ATN Ca), a poorly water-soluble 3-hydroxy 3-methyl glutaryl CoA (HMG-CoA) reductase inhibitor through inclusion complexation with beta-cyclodextrin (beta-CD). The phase solubility profile indicated that the solubility of ATN Ca was significantly increased in the presence of beta-CD and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by physical mixing, kneading, co-evaporation, and freeze-drying methods were characterized using differential scanning calorimetry, fourier transform infrared spectroscopy, and powder X-ray diffractometry. In vitro studies showed that the solubility and dissolution rate of ATN Ca were significantly improved by complexation with beta-CD with respect to the drug alone. In contrast, freeze-dried product showed higher solubility and dissolution rates than the other complexes. ATN Ca unit dosage form was developed and evaluated for physico-chemical properties, stability, and dissolution rate. The stability of tablets was studied and no significant changes were detected in the dissolution profile of tablets after 1 month.


16-Detector multislice CT-skeletal scintigraphy image co-registration.
Co-registration of bone scintigrams with radiographs has been used in the diagnosis of wrist injuries, although co-registration of tomographic bone scintigraphy with computed tomography (CT) has not been widely reported. We describe a co-registration technique in patients with possible wrist fracture. The technique was used on three patients and involved placing the wrist on a Perspex board and tracing the outline of the forearm and hand with a pen to try and ensure accurate repositioning on the board for the two sets of imaging. Four point source markers were attached to the board during both examinations. Single photon emission computed tomography (SPECT) was performed 4 h after injection Tc-methylenediphosphonate (MDP), using a dual-headed gamma camera. CT images were acquired on a 16-detector CT unit. The SPECT and CT images were co-registered with commercially available image fusion software. The centre of the four markers was identified in both sets of images and a rigid body point match algorithm was used. Before patient studies, the technique was tested using a phantom. In all the phantom and clinical studies it was possible to identify the positions of all the markers. There were varying degrees of success in patient repositioning. We describe a technique that may aid the fusion of functional images from skeletal scintigraphy with the exquisite anatomical detail from the latest CT technology, in the detection of occult wrist fractures. The technique may aid fracture localization and/or detection and might help distinguish the clinically important scaphoid fractures from other benign carpal lesions.


CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt.
The permeability-glycoprotein efflux-transporter encoded by the multidrug resistance 1 (ABCB1) gene and the cytochromes P450 3A4/5 encoded by the CYP3A4/5 genes are known to interact in the transport and metabolism of many drugs. Recent data have shown that the CYP3A5 genotypes influence blood pressure and that permeability-glycoprotein activity might influence the activity of the renin-angiotensin system. Hence, these 2 genes may contribute to blood pressure regulation in humans. We analyzed the association of variants of the ABCB1 and CYP3A5 genes with ambulatory blood pressure, plasma renin activity, plasma aldosterone, endogenous lithium clearance, and blood pressure response to treatment in 72 families (373 individuals; 55% women; mean age: 46 years) of East African descent. The ABCB1 and CYP3A5 genes interact with urinary sodium excretion in their effect on ambulatory blood pressure (daytime systolic: P=0.05; nighttime systolic and diastolic: P<0.01), suggesting a gene-gene-environment interaction. The combined action of these genes is also associated with postproximal tubular sodium reabsorption, plasma renin activity, plasma aldosterone, and with an altered blood pressure response to the angiotensin-converting enzyme inhibitor lisinopril (P<0.05). This is the first reported association of the ABCB1 gene with blood pressure in humans and demonstration that genes encoding for proteins metabolizing and transporting drugs and endogenous substrates contribute to blood pressure regulation.


Pathophysiology of artificial aqueous drainage in primate eyes with molteno implants.
Single-plate Molteno implants were installed in two stages in glaucomatous monkey eyes. This device shunts aqueous from the anterior chamber to periocular orbital tissues. The mechanism of aqueous filtration and absorption was explored using flow studies, fluorescently labeled microspheres and histological examination of tissues. Flow studies indicated that the capsule around the explant functions by a passive mechanism, shunting aqueous into the extracellular space. Outflow is proportional to capsule surface area. Latex microspheres (0.2 mum and smaller) passed freely through the capsule, giving the impression of an open sieve. The presence of microspheres in the episcleral wall of the capsule indicates that all surfaces contribute to filtration. A concentration gradient of particles in the extracapsular space, away from the bleb surface, suggests that the capsule itself limits filtration rate.


Is Anterior Rotation of the Acetabulum Necessary to Normalize Joint Contact Pressure in Periacetabular Osteotomy? A Finite-element Analysis Study.
Inappropriate sagittal plane correction can result in an increased risk of osteoarthritis progression after periacetabular osteotomy (PAO). Individual and postural variations in sagittal pelvic tilt, along with acetabular deformity, affect joint contact mechanics in dysplastic hips and may impact the direction and degree of acetabular correction. Finite-element analyses that account for physiologic pelvic tilt may provide valuable insight into the effect of PAO on the contact mechanics of dysplastic hips, which may lead to improved acetabular correction during PAO. We performed virtual PAO using finite-element models with reference to the standing pelvic position to clarify (1) whether lateral rotation of the acetabulum normalizes the joint contact pressure, (2) risk factors for abnormal contact pressure after lateral rotation of the acetabulum, and (3) whether additional anterior rotation of the acetabulum further reduces contact pressure. Between 2016 and 2020, 85 patients (92 hips) underwent PAO to treat hip dysplasia. Eighty-two patients with hip dysplasia (lateral center-edge angle < 20°) were included. Patients with advanced osteoarthritis, femoral head deformity, prior hip or spine surgery, or poor-quality images were excluded. Thirty-eight patients (38 hips) were eligible to participate in this study. All patients were women, with a mean age of 39 ± 10 years. Thirty-three women volunteers without a history of hip disease were reviewed as control participants. Individuals with a lateral center-edge angle < 25° or poor-quality images were excluded. Sixteen individuals (16 hips) with a mean age of 36 ± 7 years were eligible as controls. Using CT images, we developed patient-specific three-dimensional surface hip models with the standing pelvic position as a reference. The loading scenario was based on single-leg stance. Four patterns of virtual PAO were performed in the models. First, the acetabular fragment was rotated laterally in the coronal plane so that the lateral center-edge angle was 30°; then, anterior rotation in the sagittal plane was added by 0°, 5°, 10°, and 15°. We developed finite-element models for each acetabular position and performed a nonlinear contact analysis to calculate the joint contact pressure of the acetabular cartilage. The normal range of the maximum joint contact pressure was calculated to be < 4.1 MPa using a receiver operating characteristic curve. A paired t-test or Wilcoxon signed rank test with Bonferroni correction was used to compare joint contact pressures among acetabular positions. We evaluated the association of joint contact pressure with the patient-specific sagittal pelvic tilt and acetabular version and coverage using Pearson or Spearman correlation coefficients. An exploratory univariate logistic regression analysis was performed to identify which of the preoperative factors (CT measurement parameters and sagittal pelvic tilt) were associated with abnormal contact pressure after lateral rotation of the acetabulum. Variables with p values < 0.05 (anterior center-edge angle and sagittal pelvic tilt) were included in a multivariable model to identify the independent influence of each factor. Lateral rotation of the acetabulum decreased the median maximum contact pressure compared with that before virtual PAO (3.7 MPa [range 2.2-6.7] versus 7.2 MPa [range 4.1-14 MPa], difference of medians 3.5 MPa; p < 0.001). The resulting maximum contact pressures were within the normal range (< 4.1 MPa) in 63% of the hips (24 of 38 hips). The maximum contact pressure after lateral acetabular rotation was negatively correlated with the standing pelvic tilt (anterior pelvic plane angle) (ρ = -0.52; p < 0.001) and anterior center-edge angle (ρ = -0.47; p = 0.003). After controlling for confounding variables such as the lateral center-edge angle and sagittal pelvic tilt, we found that a decreased preoperative anterior center-edge angle (per 1°; odds ratio 1.14 [95% CI 1.01-1.28]; p = 0.01) was independently associated with elevated contact pressure (≥ 4.1 MPa) after lateral rotation; a preoperative anterior center-edge angle < 32° in the standing pelvic position was associated with elevated contact pressure (sensitivity 57%, specificity 96%, area under the curve 0.77). Additional anterior rotation further decreased the joint contact pressure; the maximum contact pressures were within the normal range in 74% (28 of 38 hips), 76% (29 of 38 hips), and 84% (32 of 38 hips) of the hips when the acetabulum was rotated anteriorly by 5°, 10°, and 15°, respectively. Via virtual PAO, normal joint contact pressure was achieved in 63% of patients by normalizing the lateral acetabular coverage. However, lateral acetabular rotation was insufficient to normalize the joint contact pressure in patients with more posteriorly tilted pelvises and anterior acetabular deficiency. In patients with a preoperative anterior center-edge angle < 32° in the standing pelvic position, additional anterior rotation is expected to be a useful guide to normalize the joint contact pressure. This virtual PAO study suggests that biomechanics-based planning for PAO should incorporate not only the morphology of the hip but also the physiologic pelvic tilt in the weightbearing position in order to customize acetabular reorientation for each patient.


Effect of spray-dried mannitol on the performance of microcrystalline cellulose-based wet granulated tablet formulation.
The purpose of this study was to evaluate mannitol as filler along with microcrystalline cellulose (MCC) in wet granulated tablet formulation, in situations where lactose cannot be included in the formulation due to chemical incompatibility with the active drug. A two-level full factorial design with two center points was used to study the effect of three variables: mannitol: MCC ratio (mannitol weight fraction of the filler; low 0 (no mannitol) and high 0.5), water to intragranular solids ratio (low 0.25 and high 0.4) and magnesium stearate concentration, w/w (0.6% low and 1.2% high). The response variables evaluated were granulation compactibility, ejection force, normalized granule size, % fines, flowability index, compression speed sensitivity and hardness loss upon storage. Addition of mannitol in the MCC formulation increased compactibility of the final granulation as it decreased the susceptibility of the formulation to compaction loss upon wet granulation. Presence of mannitol in the formulation reduced the compression speed sensitivity and also decreased the susceptibility of the formulation to hardness loss upon storage.


Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development.
Although the knowledge that nuclear and cytoplasmic proteins are modified with N-acetylglucosamine has existed for decades, little has been shown as to its function until recently. There are now substantial data highlighting the significance of proper regulation of this modification in multiple cellular processes. Currently, only two enzymes are known that regulate this modification. O-GlcNAc transferase (OGT) modifies protein substrates posttranslationally by adding the N-acetylglucosamine. Bifunctional nuclear/cytoplasmic O-GlcNAcase and acetyl transferase (NCOAT) is responsible for cleaving the modification from target proteins. Here, we demonstrate for the first time an unusual association of these two opposing enzymes into a single O-GlcNAczyme complex. NCOAT and OGT associate strongly through specific domains such that NCOAT accompanies OGT, with histone deacetylases (HDACs), into transcription corepression complexes. Exclusion of NCOAT activities from OGT association blocks proper estrogen-dependent cell signaling as well as mammary development in transgenic mice. This demonstrates that NCOAT is in a strategic position to rapidly counteract OGT and HDAC without requiring its recruitment.


Total body irradiation versus busulfan based intermediate intensity conditioning for stem cell transplantation in ALL patients >45 years-a registry-based study by the Acute Leukemia Working Party of the EBMT.
Allogeneic hematopoietic cell transplantation is a potentially curative treatment in high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens based on ≥12 Gray total body irradiation (TBI) represent the current standard in patients ≤45 years, whereas elderly patients frequently receive intermediate intensity conditioning (IIC) to reduce toxicity. To evaluate the role of TBI as a backbone of IIC in ALL, a retrospective, registry-based study included patients >45 years transplanted from matched donors in first complete remission, who had received either fludarabine/TBI 8 Gy (FluTBI8, n = 262), or the most popular, irradiation-free alternative fludarabine/busulfan, comprising busulfan 6.4 mg/kg (FluBu6.4, n = 188) or 9.6 mg/kg (FluBu9.6, n = 51). At two years, overall survival (OS) was 68.5%, 57%, and 62.2%, leukemia-free survival (LFS) was 58%, 42.7%, and 45%, relapse incidence (RI) was 27.2%, 40%, and 30.9%, and non-relapse-mortality (NRM) was 23.1%, 20.7%, and 26.8% for patients receiving FluTBI8Gy, FluBu6.4, and FluBu9.6, respectively. In multivariate analysis, the risk of NRM, acute and chronic graft-versus-host disease was not influenced by conditioning. However, RI was higher after FluBu6.4 (hazard ratio [HR] [95% CI]: 1.85 [1.16-2.95]), and LFS was lower after both FluBu6.4 (HR: 1.56 [1.09-2.23]) and FluBu9.6 (HR: 1.63 [1.02-2.58]) as compared to FluTBI8. Although only resulting in a non-significant advantage in OS, this observation indicates a stronger anti-leukemic efficacy of TBI-based intermediate intensity conditioning.


Catalase-mimetic gold nanoparticles inhibit the antagonistic action of Lactobacillus gasseri toward foodborne enteric pathogens in associative cultures.
Gold nanoparticles (AuNPs) have been previously shown to induce gut dysbiosis during colitis in mice, but the underlying mechanism is not clear yet. Here, we evaluated the effects of AuNPs (5 nm diameter, coated with tannic acid, polyvinylpyrrolidone or citrate) on H2O2 accumulation and pathogen antagonization by an intestinal strain of Lactobacillus gasseri under aerobic cultural conditions. AuNPs (0.65 μg/mL) reduced over 50% of H2O2 accumulation by L. gasseri, and significantly inhibited the antagonistic action of L. gasseri on growth of four foodborne enteric pathogens, i.e. Salmonella enterica serovar Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus in associative cultures.


Prevalence and characteristics of restless legs syndrome (RLS) in the elderly and the relation of serum ferritin levels with disease severity: hospital-based study from Istanbul, Turkey.
The RLS is an underdiagnosed condition, characterized by unpleasant sensations in the legs. Pathophysiological mechanisms may include iron deficiency as reflected by low serum ferritin levels and dopaminergic system dysfunction. The purpose of our study was to investigate the prevalence and characteristics of RLS in the elderly and the relation of serum ferritin levels with disease severity. Ambulatory 1012 (621 women, 391 men, mean age: 73.51 ± 7.12 years) consecutive patients above 65 years who admitted to our clinic for any reason were evaluated according to the International RLS Study Group (IRLSSG) criteria: 103 patients (74 women, 29 men, mean age: 72.43 ± 6.31) (10.18%) had RLS diagnosis. Only 9 of them had known RLS. The duration of symptoms was 4.80 ± 4.65 years and 27 patients (26.2%) had positive family history. The average of serum ferritin levels was 39.13 ± 23.74 ng/ml and 71 patients (68.9%) had serum ferritin levels ≤ 50 ng/ml. The disease severity was evaluated with IRLSSG rating scale. Patients were classified as severe-very severe group (n=49) and mild-moderate group (n=54). The ferritin levels of severe-very severe disease group were lower than those of mild-moderate disease group (26.01 ± 15.82 ng/ml versus 49.87 ± 23.24 ng/ml, p<0.001). Our data show that RLS is very common in the elderly and the disease is more severe in patients with lower ferritin levels.


[Inhibitory effects of matrix metalloproteinase (MMP) inhibitor LY52 on expression of MMP-2 and MMP-9 and invasive ability of human ovarian carcinoma cell line SKOV3].
Enhanced expression and activation of matrix metalloproteinase-2 (MMP-2) and MMP-9 are associated with tumor progression, invasion, and metastasis. Using synthetic MMP inhibitors to block the proteolytic activity of these enzymes is a potential strategy of treating cancer. This study was to observe the inhibitory effects of LY52, a synthetic specific MMP inhibitor, on the expression of MMP-2 and MMP-9 and invasive ability of human ovarian carcinoma cell line SKOV3. The inhibitory effect of LY52 on growth of SKOV3 cells was measured by MTT and clonogenic assays. The inhibitory effect of LY52 on the activity of gelatin was evaluated by spectrophotometry using succinylated gelatin as substrate. The inhibitory effect of LY52 on the expression of MMP-2 and MMP-9 was analyzed using SDS-PAGE zymography. The adhesive ability of SKOV3 cells to fibronectin (FN), laminin (LN), and matrigel was measured using MTT assay. The invasive ability of SKOV3 cells was assessed with a transwell cell culture chamber. LY52 had weak cytostatic effect on SKOV3 cells, the inhibitory rates were 10.54%-37.66% within 120 h incubation when the concentration was 10 microg/ml. LY52 inhibited gelatin degradation via suppressing the activities of gelatinases, the 50% inhibitory concentration (IC50) was 11.9 microg/ml. When treated with 0.1, 1, 10, 100, or 1,000 microg/ml LY52 for 24 h, the expression of MMP-2 in SKOV3 cells was suppressed by 10.66%-31.47%, and the expression of MMP-9 was suppressed by 22.56%-56.71%. When treated with LY52 for 1 h, the maximum inhibitory rates of adhesion of SKOV3 cells to FN, LN, and matrigel were 29.79%, 48.94%, and 50.92%, respectively. When treated with 0.1, 1, 10, 100, and 1,000 microg/ml LY52 for 24 h, the inhibitory rates of invasion of SKOV3 cells were 7.5%, 42.07%, 66.54%, 72.15%, and 82.84%, respectively. LY52 suppresses the invasion of SKOV3 cells via inhibiting the expression of MMP-2 and MMP-9.


Endophthalmitis Following Strabismus Surgery: IPOSC Global Study.
To examine the characteristics of patients with endophthalmitis after strabismus surgery (PSSE), the characteristics of the strabismus surgery, treatment, and prognosis as reported by pediatric ophthalmologists who are members of the American Association for Pediatric Ophthalmology and Strabismus (AAOPS) around the world. An email communication was sent to all members of AAPOS. The email included a web link to a survey that included 34 questions that examined the characteristics of patients with endophthalmitis after strabismus surgery. Three hundred forty-nine ophthalmologists responded to the questionnaire. Two hundred sixty four (76%) had practiced pediatric ophthalmology for over 10 years. Twenty-seven cases of endophthalmitis were reported. The medial rectus muscle (MR) was the most common muscle undergoing surgery (55%). In 5 patients (21%), perforation was observed at the time of surgery. In all cases, endophthalmitis was diagnosed 3-7 days after surgery. The final visual acuity of 34% was no light perception (NLP). This series is the largest existing series on PSSE. Our data suggest that PSSE can occur also in healthy patients and in patients without a visualized scleral perforation. The majority of PSSE occurs during the first week after surgery. Therefore, we believe that all patients that underwent strabismus surgery should be examined in this time frame. The prognosis was poor with 48% demonstrating a visual acuity of LP or NLP at the final follow-up.


A hydrothermally grown CdS nanograin-sensitized 1D Zr:α-Fe2O3/FTO photoanode for efficient solar-light-driven photoelectrochemical performance.
Well-defined CdS nanograin-sensitized one-dimensional (1D) Zr:α-Fe2O3 nanostructured arrays with enhanced photoelectrochemical performance are synthesized directly on F-doped SnO2 (FTO) using the hydrothermal method. Owing predominantly to the appropriate photogenerated electron-hole separation and charge collection in 1D Zr:α-Fe2O3 nanorods, hydrothermally deposited CdS/1D Zr:α-Fe2O3 samples exhibit improved photocurrent density over CdS/Fe2O3 nanosheets prepared by other methods. In our work, compared with 1D Zr:α-Fe2O3, the CdS-sensitized 1D Zr:α-Fe2O3 nanorod arrays show 1.9 times improved photoelectrochemical performance. Unfortunately, CdS nanograin-sensitized 1D Zr:α-Fe2O3 nanorod arrays suffer from instability problem. Nickel hydroxide loading, however, can boost the photoelectrochemical performance of the heterojunction and also act as a protective layer that improves the stability of the Ni(OH)2/CdS/1D Zr:α-Fe2O3 electrode compared to CdS/1D Zr:α-Fe2O3. This enhanced PEC activity may be ascribed to the strong heterojunctions between CdS nanograins and 1D Zr:α-Fe2O3 nanorod arrays as well as effective charge separation. This work will provide a new insight into the fabrication and protection of many new photosensitive electrode materials to engineer photoelectrochemical and photocatalytic devices in the near future.


Environmental correlates of temporal variation in the prey species of Australian fur seals inferred from scat analysis.
Marine ecosystems in southeastern Australia are responding rapidly to climate change. We monitored the diet of the Australian fur seal (Arctocephalus pusillus doriferus), a key marine predator, over 17 years (1998-2014) to examine temporal changes. Frequency of occurrence (FO) of prey was used as a proxy for ecosystem change. Hard part analysis identified 71 prey taxa, with eight dominant taxa in greater than 70% of samples and predominantly included benthic and small pelagic fish. FO changed over time, e.g. redbait (Emmelichthys nitidus) reduced after 2005 when jack mackerel (Trachurus declivis) increased, and pilchard (Sardinops sajax) increased after 2009. Using generalized additive models, correlations between FO and environmental variables were evident at both the local (e.g. wind, sea surface temperature (SST)) and regional (e.g. El Niño-Southern Oscillation Index (SOI), Southern Annular Mode (SAM)) scales, with redbait and pilchard showing the best model fits (greater than 75% deviance explained). Positive SAM was correlated to FO for both species, and wind and season were important for redbait, while SOI and SST were important for pilchard. Both large-scale and regional processes influenced prey taxa in variable ways. We predict that the diverse and adaptable diet of the Australian fur seal will be advantageous in a rapidly changing ecosystem.


Development of construction materials using nano-silica and aggregates recycled from construction and demolition waste.
The present work addresses the development of novel construction materials utilising commercial grade nano-silica and recycled aggregates retrieved from construction and demolition waste. For this, experimental work has been carried out to examine the influence of nano-silica and recycled aggregates on compressive strength, modulus of elasticity, water absorption, density and volume of voids of concrete. Fully natural and recycled aggregate concrete mixes are designed by replacing cement with three levels (0.75%, 1.5% and 3%) of nano-silica. The results of the present investigation depict that improvement in early days compressive strength is achieved with the incorporation of nano-silica in addition to the restoration of reduction in compressive strength of recycled aggregate concrete mixes caused owing to the replacement of natural aggregates by recycled aggregates. Moreover, the increase in water absorption and volume of voids with a reduction of bulk density was detected with the incorporation of recycled aggregates in place of natural aggregates. However, enhancement in density and reduction in water absorption and volume of voids of recycled aggregate concrete resulted from the addition of nano-silica. In addition, the results of the study reveal that nano-silica has no significant effect on elastic modulus of concrete.


Bacteriology of selective decontamination: efficacy and rebound colonization.
In earlier studies concerning the use of selective decontamination (SD) we recognized some patients to have an incomplete or failed decontamination which had negative consequences for their outcome. We also experienced patients to have a rebound colonization with potentially pathogenic microorganisms (PPM) after the withdrawal of SD medication, thereby endangering the hospital environment as sources of possibly resistant microorganisms. In a prospective observational cohort-study, we have studied 135 patients on a surgical ICU in a University hospital. On admission 51% of all patients harboured PPM, of which 64% and 79% were eliminated form the oropharynx and gut, respectively. A total of 49 episodes of SD (32%) had to be defined as ineffective, partly due to late or inadequate administration of medication. Rebound colonization with nosocomial aerobic PPM was seen in 20 of 90 successfully decontaminated episodes, but there were no infections. Eighty-four of 123 surveillance cultures (68%) revealed a complete recolonization with flora in a composition not different from the pre-admission flora. Withdrawal of SD medication 5 days after extubation proved satisfactory because no infections ensued. Surveillance cultures are obligatory to determine whether SD is effective as one third of patients receiving SD experienced bacterial colonization with PPM and therefore had no benefit from this prophylaxis. In addition, these results indicate that an intact and functional colonization resistance develops in patients after cessation of effective SD medication, but only when physiological defence mechanisms are presumably restored. In the seven years of experience with SD, increasing antibiotic resistance has not been in the study hospital.


Frequency and diversity of use of statistical techniques in oncology journals.
We describe the frequency with which various statistical techniques are reported in almost 5,000 articles published in five major American oncology journals during 1983 and 1984. A reader familiar with about a dozen techniques can expect to understand approximately 90% of the quantitative concepts cited in these journals. With the exception of survival analysis, these were typically the techniques encountered in many introductory statistical texts. Oncology training program preceptors concerned about making their graduates more effective consumers of the literature can use these findings in structuring exposure to quantitative skills. In four of the five journals reviewed, failure to identify the statistical methodology was among the ten most commonly encountered "techniques." This made it impossible to identify the analytical procedures used in many articles, and hence to judge their scientific validity. We encourage more editorial boards to adopt guidelines requiring a standardized format for presenting results based on a statistical analysis.


Pulmonary vein activation in atrial fibrillation and sinus rhythm.
The purpose of this study was to determine the relationship between pulmonary vein (PV) electrical activation during atrial fibrillation (AF) and after cardioversion into sinus rhythm. Electrograms were recorded using a circular mapping catheter during AF and after cardioversion in 53 PVs from 41 patients. Two activation patterns were observed in AF. Group 1 had fixed, consistent, uniform activation sequences most (>70%) of the recording time. Group 2 had no fixed activation sequence. In Group 1, a constant single activation sequence pattern was seen in 22 PVs (Group 1a). The earliest PV activation sites were the same during AF and after cardioversion to sinus rhythm in 17 (77%) PVs from Group 1a. Fourteen of these 17 (82%) cases also had a common site of electrogram polarity reversal. In Group 2, a relationship between PV activation before and after cardioversion was not found. Segmental radio frequency (RF) ablation was performed during sinus rhythm after cardioversion. There was no difference in the number of atriovenous breakthroughs between the two groups (1.9+/-0.7 vs. 2.0+/-0.6 breakthroughs, P=NS). PV disconnection was achieved in all PVs with a mean RF duration of 13.5+/-4.5 min per vein in Group 1 and 14.0+/-4.9 min per vein in Group 2 (P=NS). A uniform PV electrogram pattern recorded during AF usually predicts the activation sequence and/or the polarity reversal sites during sinus rhythm. This pattern does not necessarily suggest a single atriovenous breakthrough point.


How Has COVID-19 Changed the Way We Do Virtual Care? A Scoping Review Protocol.
The coronavirus disease (COVID-19) pandemic created worldwide interest and use of virtual care to support public health measures and reduce the spread of infection. While some forms of virtual care have been used prior to COVID-19 such as telemedicine, little is known about other virtual modalities such as video conferencing, wearables and other digital technologies. The COVID-19 pandemic has presented an opportunity to question the efficacy and safety of virtual care, especially in terms of patient outcomes among those self-isolating. The purpose of this scoping review is to examine the safety of virtual care among active COVID-19 patients in the community and examine the types and dose of virtual care. Finally, this review will examine what patient outcomes are identified from interventions delivered virtually to treat COVID-19. We followed a systematic process guided by the PRISMA checklist for scoping reviews with a comprehensive search strategy across four bibliographic databases and handsearching reference lists. We undertook a blinded, two-stage screening process with eligibility criteria. All citations and screening were managed using the DistillerSR software. Data were extracted using a data extraction tool developed for this project. The conclusions from this review will offer greater understanding for how virtual care can be used among community-based COVID-19 patients.


Association between Precipitation and Diarrheal Disease in Mozambique.
Diarrheal diseases are a leading cause of morbidity and mortality in Africa. Although research documents the magnitude and pattern of diarrheal diseases are associated with weather in particular locations, there is limited quantification of this association in sub-Saharan Africa and no studies conducted in Mozambique. Our study aimed to determine whether variation in diarrheal disease was associated with precipitation in Mozambique. In secondary analyses we investigated the associations between temperature and diarrheal disease. We obtained weekly time series data for weather and diarrheal disease aggregated at the administrative district level for 1997-2014. Weather data include modeled estimates of precipitation and temperature. Diarrheal disease counts are confirmed clinical episodes reported to the Mozambique Ministry of Health (n = 7,315,738). We estimated the association between disease counts and precipitation, defined as the number of wet days (precipitation > 1 mm) per week, for the entire country and for Mozambique's four regions. We conducted time series regression analyses using an unconstrained distributed lag Poisson model adjusted for time, maximum temperature, and district. Temperature was similarly estimated with adjusted covariates. Using a four-week lag, chosen a priori, precipitation was associated with diarrheal disease. One additional wet day per week was associated with a 1.86% (95% CI: 1.05-2.67%), 1.37% (95% CI: 0.70-2.04%), 2.09% (95% CI: 1.01-3.18%), and 0.63% (95% CI: 0.11-1.14%) increase in diarrheal disease in Mozambique's northern, central, southern, and coastal regions, respectively. Our study indicates a strong association between diarrheal disease and precipitation. Diarrheal disease prevention efforts should target areas forecast to experience increased rainfall. The burden of diarrheal disease may increase with increased precipitation associated with climate change, unless additional health system interventions are undertaken.


Ultrasound analysis of the relationship between right internal jugular vein and common carotid artery in the left head-rotation and head-flexion position.
Common carotid artery (CCA) injury is a serious complication of internal jugular vein (IJV) cannulation. To minimize unintentional CCA puncture, the anatomic relationship between the IJV and the CCA and the size of IJV were compared under different head positions. Ultrasound analyses of the IJV and the CCA were performed in 103 consecutive patients. Overlapping angle (OA), real puncture angle (RPA) and diameter of IJV (D IJV) were evaluated with 30° and 60° left rotation and with 30° left flexion. When the head position was changed from 30° left rotation to 60° left rotation, OA increased significantly from 6.5° ± 7.7° to 14.5° ± 7.4° at the cricoid cartilage level (Cricoid-level) and from 14.4° ± 8.4° to 20.6° ± 6.9° at the middle triangle level (Triangle-level), whereas RPA decreased significantly at these levels (from 49.7° ± 11.9° to 43.5° ± 13.1° and from 51.1° ± 14.4° to 44.3° ± 13.9°, respectively; P < 0.01 for both). When the head position was changed from 30° left rotation to 30° left flexion, neither OA nor RPA significantly changed (OA: 6.3° ± 6.1° and 15.0° ± 7.2°, RPA: 48.5° ± 12.4° and 51.8° ± 13.6°, P not significant vs 30° left rotation). There was no difference in D IJV when comparing 30° left rotation and 30° left flexion, although D IJV was largest at 60° left rotation. RPA positively correlated with age, and D IJV positively correlated with body mass index. In conclusion, excessive left rotation should be avoided to minimize the probability of unintentional CCA puncture during IJV cannulation. When 30° left rotation is not feasible, the head-flexion position should be utilized.


[Cocaine and cerebrovascular disease in young adults].
The use of cocaine has been increasingly associated with cerebrovascular disease specially in young adults. We review the cases of stroke related to cocaine abuse in this group. We performed a retrospective study between 1989-1998. Data were obtained from the Young Adults Stroke Registry. To investigate the etiology of stroke all patients underwent cardiologic examination, coagulation and neuroimaging tests. We identified 13 patients under 45 years of age with stroke related to cocaine abuse (0.39% of all strokes and 7.60% of the ones in young adults). Mean age in this group was 28.30 years. Eight developed ischemic manifestations (5 infarcts, 2 TIAs and 1 encephalopathy with multiple ischemic lesions), 4 had intraparenchymal hemorrhages and 1 had a subarachnoid hemorrhage. The principal route of administration was intranasal and the time course from cocaine use to stroke ranged from several hours to several years. 61.53% had history of other drug abuse and in 84.61% other risk factors were identified. Angiographic studies demonstrated: arterial occlusions (3 cases), changes consistent with vasospasm (1), segmental narrowing (1) and arterial wall irregularities (1). No aneurysms or arterio-venous malformations were found. The frequency of cocaine-related stroke in young adults has decreased from 8.33% in 1989 to 5% in 1998. Cocaine is a well known cause of stroke, specially in young adults. In most cases other risk factors can be identified. Multiple overlapping mechanisms may be involved (vasospasm-thrombosis, high blood pressure, embolism.


Characterization and Comparative Analysis of Chloroplast Genomes in Five Uncaria Species Endemic to China.
Uncaria, a perennial vine from the Rubiaceae family, is a typical Chinese traditional medicine. Currently, uncertainty exists over the Uncaria genus' evolutionary relationships and germplasm identification. The complete chloroplast genomes of four Uncaria species mentioned in the Chinese Pharmacopoeia and Uncaria scandens (an easily confused counterfeit) were sequenced and annotated. The findings demonstrated that the whole chloroplast genome of Uncaria genus is 153,780-155,138 bp in full length, encoding a total of 128-131 genes, containing 83-86 protein-coding genes, eight rRNAs and 37 tRNAs. These regions, which include eleven highly variable loci and 31-49 SSRs, can be used to create significant molecular markers for the Uncaria genus. The phylogenetic tree was constructed according to protein-coding genes and the whole chloroplast genome sequences of five Uncaria species using four methods. The topology of the two phylogenetic trees showed no difference. The sequences of U. rhynchophylla and U. scandens are clustered in one group, while the U. hirsuta and U. macrophylla are clustered in another group. U. sessilifructus is clustered together with the above two small clades. New insights on the relationship were revealed via phylogenetic research in five Uncaria species. This study will provide a theoretical basis for identifying U. rhynchophylla and its counterfeits, as well as the species of the Uncaria genus. This research provides the initial chloroplast genome report of Uncaria, contributes to elucidating the chloroplast genome evolution of Uncaria in China.


Upregulation of lncRNA HAGLROS enhances the development of nasopharyngeal carcinoma via modulating miR-100/ATG14 axis-mediated PI3K/AKT/mTOR signals.
We planned to dig the significant role of long noncoding RNA HAGLROS in nasopharyngeal carcinoma (NPC) and the latent mechanism. The levels of HAGLROS in NPC tissues and cells were determined, followed by correlation analysis of HAGLROS level and clinicopathological features of patients suffered with NPC. The impacts of HAGLROS dysregulation on NPC cell viability, apoptosis, and the expression of apoptotic proteins and autophagy-related symbols were investigated. Moreover, we explored whether HAGLROS modulated the expression of autophagy-related gene 14 (ATG14) by competitively sponging miR-100, and then regulated the briskness of PI3K/AKT/mTOR signals in NPC development. HAGLROS level in NPC tissues and cell was very high. High level of HAGLROS indicated a short overall survival in NPC patients. Depressing of HAGLROS lessened NPC cell viability, enhanced apoptosis and reduced autophagy. Besides, HAGLROS negative controlled miR-100 and consequently targeted ATG14 expression, thus modulating NPC cell viability, apoptosis, and autophagy. Besides, dysregulation of HAGLROS/miR-100/ATG14 axis was correlated to the briskness of PI3K/AKT/mTOR signals in NPC cells. Our results indicate that of the augment of HAGLROS contributes to NPC development via modulating miR-100/ATG14 axis-mediated PI3K/AKT/mTOR signals. Our study will offer a comprehensive basis for better illustrating the pathogenesis of NPC. Highlights HAGLROS expression was upregulated in NPC tissues and cells. High expression of HAGLROS indicated a short overall survival in NPC patients. Silencing of HAGLROS promoted apoptosis and inhibited autophagy of NPC cells. HAGLROS regulated ATG14 expression in NPC cells via sponging miR-100. HAGLROS/miR-100/ATG14 axis regulated NPC development via PI3K/AKT/mTOR pathway.


Sudden cardiac arrest in a patient with an anomalous left main coronary artery originating from the pulmonary artery.
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is an uncommon cardiac abnormality. The clinical picture of ALCAPA may range from asymptomatic course with normal life span to sudden cardiac death. Moreover, from the standpoint of resuscitation science, it constitutes a disadvantageous anatomy for coronary perfusion pressure, generated by chest compressions, which is critical for the return of spontaneous circulation. Here, we report an ALCAPA case diagnosed after out-of-hospital cardiac arrest and successful cardiopulmonary resuscitation.


Developmental lessons of seasoned marital and family therapists: a qualitative investigation.
Little has been published regarding the development of therapists during their professional careers. This qualitative research study explored the development of seasoned marriage and family therapists (MFTs) in order to identify important events and themes in their personal and professional lives. The main developmental theme that emerged was the integration of their personal and professional selves. Information gained from this study might be useful in understanding the self of the therapist within training and supervision and might partially provide a map of the possible transitions facing MFTs along their developmental journey.


Disturbances in body ownership in schizophrenia: evidence from the rubber hand illusion and case study of a spontaneous out-of-body experience.
A weakened sense of self may contribute to psychotic experiences. Body ownership, one component of self-awareness, can be studied with the rubber hand illusion (RHI). Watching a rubber hand being stroked while one's unseen hand is stroked synchronously can lead to a sense of ownership over the rubber hand, a shift in perceived position of the real hand, and a limb-specific drop in stimulated hand temperature. We aimed to assess the RHI in schizophrenia using quantifiable measures: proprioceptive drift and stimulation-dependent changes in hand temperature. The RHI was elicited in 24 schizophrenia patients and 21 matched controls by placing their unseen hand adjacent to a visible rubber hand and brushing real and rubber hands synchronously or asynchronously. Perceived finger location was measured before and after stimulation. Hand temperature was taken before and during stimulation. Subjective strength of the illusion was assessed by a questionnaire. Across groups, the RHI was stronger during synchronous stimulation, indicated by self-report and proprioceptive drift. Patients reported a stronger RHI than controls. Self-reported strength of RHI was associated with schizotypy in controls Proprioceptive drift was larger in patients, but only following synchronous stimulation. Further, we observed stimulation-dependent changes in skin temperature. During right hand stimulation, temperature dropped in the stimulated hand and rose in the unstimulated hand. Interestingly, induction of RHI led to an out-of-body experience in one patient, linking body disownership and psychotic experiences. The RHI is quantitatively and qualitatively stronger in schizophrenia. These findings suggest that patients have a more flexible body representation and weakened sense of self, and potentially indicate abnormalities in temporo-parietal networks implicated in body ownership. Further, results suggest that these body ownership disturbances might be at the heart of a subset of the pathognomonic delusions of passivity.


Chromatin-Accessible miRNA Regulons Driving Thyroid Tumorigenesis and Progression.
Although papillary thyroid cancer can remain indolent, associated lymph node metastases and recurrence rates are approximately 50% and 20%, respectively. Omics-based medicine has led to the discovery of predictive biomarkers that can be used to predict tumor progression and clinical outcomes. We aimed to develop a noninvasive omics-driven blood test to allow accurate risk stratification and help tailor individual patient treatment plans. RNA sequencing (seq) and microRNA analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets were employed to identify an epigenetic prognostic panel. Integrated bulk assay for transposase-accessible chromatin-seq and RNA-seq experiments confirmed the results. Sixty-two paired tumor and adjacent control thyroid tissues and 67 blood samples (62 papillary thyroid cancer and 5 controls) were analyzed for validation using sequencing and real-time polymerase chain reaction and correlated to clinical outcomes. A liposome-exosome fusion clustered regularly interspaced short palindromic repeats (CRISPR)-fluorescent detection system miRNA assay was developed. A predictive risk nomogram was generated and tested for performance. Our miRNA panel (miR-146b-5p and miR-221-3p) from tissue and blood was associated with aggressive features and was located within accessible chromatin regions. The miRNA risk score and prognostic nomogram showed higher accuracy in predicting lymph node metastases (miR-146b: area under the curve [AUC] 0.816, sensitivity 76.9%; miR-221: AUC 0.740, sensitivity 79.5%) and recurrence (miR-146b: AUC 0.921, sensitivity 75.0%; miR-221: AUC 0.756, sensitivity 70.0%; p < 0.001) than staging and American Thyroid Association risk stratification. CRISPR-based miRNA assays showed upregulation in the blood of cancer cohorts. CRISPR-based detection of miR-146b and miR-221 in the blood of thyroid cancer patients is a reliable and noninvasive tool for real-time assessment and prognostication that has great potential to provide a direct impact on the care of these patients.


Effect of dietary protein content on ileal amino acid digestibility, growth performance, and formation of microbial metabolites in ileal and cecal digesta of early-weaned pigs.
Diarrhea incidence in weaned pigs may be associated with the concentration of intestinal microbial metabolites (ammonia, amines, and VFA) that are influenced by dietary CP content. Three experiments were conducted to determine effects of a low-protein, AA-supplemented diet on ileal AA digestibility, growth performance, diarrhea incidence, and concentration of microbial metabolites in ileal and cecal digesta of pigs weaned at 14 d of age. In Exp. 1, 8 pigs fitted with a simple T-cannula at the distal ileum were assigned in a crossover design to 2 diets containing 24 or 20% CP using wheat, corn, full-fat soybeans, whey powder, fish meal, and blood plasma as the main ingredients. Supplemental AA were added to the diets to meet the AA standards according to the 1998 NRC recommendations. Chromic oxide was used as an indigestible marker. Diets were fed at 2.5 times the ME requirement for maintenance. The reduction of dietary CP decreased (P < 0.05) the apparent ileal digestibility of most AA, except Lys, Met, Thr, Val, and Pro. Dietary CP content did not affect the pH of ileal digesta or ileal concentrations of ammonia N, cadaverine, putrescine, or VFA. In Exp. 2, 8 pigs fitted with a simple T-cannula in the cecum were assigned to 2 diets, similar to Exp. 1. Dietary CP content did not affect the pH of cecal digesta. The reduction in CP content decreased (P < 0.05) cecal ammonia N, acetic acid, isobutyric acid, isovaleric acid, total VFA, and putrescine concentrations by 28 to 39%. In Exp. 3, 32 pigs were assigned to 2 diets, similar to Exp. 1, according to a randomized complete block design. Pigs had free access to feed and water. Dietary CP content did not affect growth performance or fecal consistency scores during the 3-wk study, and diarrhea was not observed. The results of these experiments indicate that lowering the dietary CP content combined with supplementation of AA markedly reduced the production of potentially harmful microbial metabolites in cecal digesta of early-weaned pigs without affecting growth performance.


Intensive integrated therapy of type 2 diabetes: implications for long-term prognosis.
The macro- and microvascular burden of type 2 diabetes is well established. A number of recent single risk factor intervention trials targeting hyperglycemia, dyslipidemia, hypertension, procoagulation, microalbumuria, and existing cardiovascular disorders have, however, shown major beneficial effects on long-term outcome. The results from these studies are anticipated to change the future management of type 2 diabetes, and most of the updated national guidelines for the treatment of type 2 diabetes recommend a multipronged approach driven by ambitious treatment targets. The outcome of this intensive integrated therapy has, however, only been investigated in a few studies of patients with type 2 diabetes. One of these trials, the Steno-2 Study, showed that intensive intervention for an average of 7.8 years cuts cardiovascular events as well as nephropathy, retinopathy, and autonomic neuropathy by about half when compared with a conventional multifactorial treatment. The challenge for now is to ensure that the trial experiences are widely adopted in daily clinical practice.


Enhancement of the Mechanical, Self-Healing and Pollutant Adsorption Properties of Mortar Reinforced with Empty Fruit Bunches and Shell Chars of Oil Palm.
This study aims to produce mortar through the addition of oil palm shells (OPS)-activated charcoal and oil palm empty fruit bunch (OPEFB) hydrochar, which has high mechanical properties, self-healing crack capabilities, and pollutant adsorption abilities. The cracking of mortar and other cementitious materials is essential in anticipating and reducing building damages and ages due to various reasons, such as chemical reactions, foundation movements, climatic changes, and environmental stresses. This leads to the creation of self-healing mortar, which is produced by adding reductive crack size materials to form calcium carbonate (CaCO3) and silicate hydrate (3CaO.2SiO2.2H2O, CSH). One of these materials is known as activated charcoal, which is obtained from oil palm shells (OPS) and oil palm empty fruit bunches (OPEFB) fibres. This is because the OPS-activated charcoal minimizes crack sizes and functions as a gaseous pollutant absorber. In this study, activated charcoal was used as fine aggregate to substitute a part of the utilized sand. This indicated that the utilized content varied between 1-3 wt.% cement. Also, the mortar samples were tested after 28 days of cure, including the mechanical properties and gaseous pollutant adsorption abilities. Based on this study, the crack recovery test was also performed at specific forces and wet/dry cycles, respectively, indicating that the mortar with the addition of 3% activated charcoal showed the best characteristics. Using 3% of the cement weight, OPEFB hydrochar subsequently varied at 1, 2, and 3% of the mortar volume, respectively. Therefore, the mortar with 3 and 1% of OPS-activated charcoal and OPEFB hydrochar had the best properties, based on mechanical, self-healing, and pollutant adsorption abilities.


Emerging Enteroviruses Causing Hand, Foot and Mouth Disease, China, 2010-2016.
Coxsackievirus A6 emerged as one of the predominant causative agents of hand, foot and mouth disease epidemics in many provinces of China in 2013 and 2015. This virus strain accounted for 25.9% of mild and 15.2% of severe cases in 2013 and 25.8% of mild and 16.9% of severe cases in 2015.


Spin conserving natural orbital functional theory.
The natural orbital functional theory is considered for spin uncompensated systems, i.e., systems that have one or more unpaired electrons. The well-known cumulant expansion is used to reconstruct the two-particle reduced density matrix. A new condition to ensure the conservation of the total spin is obtained for the two-particle cumulant matrix. An extension of the Piris natural orbital functional 1 (PNOF1), based on an explicit form for the cumulant, to spin uncompensated systems is also considered. The theory is applied to the calculation of energy differences between the ground state and the lowest lying excited state with different spins for first-row atoms (Li, Be, B, C, N, O, and F) and diatomic oxygen molecule (O(2)). The values we obtained are very accurate results as compared to the CCSD(T) method and the experimental data.


Species identification within Acinetobacter calcoaceticus-baumannii complex using MALDI-TOF MS.
Acinetobacter baumannii, one of the more clinically relevant species in the Acinetobacter genus is well known to be multi-drug resistant and associated with bacteremia, urinary tract infection, pneumonia, wound infection and meningitis. However, it cannot be differentiated from closely related species such as Acinetobacter calcoaceticus, Acinetobacter pittii and Acinetobacter nosocomialis by most phenotypic tests and can only be differentiated by specific, time consuming genotypic tests with very limited use in clinical microbiological laboratories. As a result, these species are grouped into the A. calcoaceticus-A. baumannii (Acb) complex. Herein we investigated the mass spectra of 73 Acinetobacter spp., representing ten different species, using an AB SCIEX 5800 MALDI-TOF MS to differentiate members of the Acinetobacter genus, including the species of the Acb complex. RpoB gene sequencing, 16S rRNA sequencing, and gyrB multiplex PCR were also evaluated as orthogonal methods to identify the organisms used in this study. We found that whilst 16S rRNA and rpoB gene sequencing could not differentiate A. pittii or A. calcoaceticus, they can be differentiated using gyrB multiplex PCR and MALDI-TOF MS. All ten Acinetobacter species investigated could be differentiated by their MALDI-TOF mass spectra.


Rigorous coupled wave analysis upgraded with combined boundary conditions method for 2D metamaterials in microwave.
We combine rigorous coupled wave analysis (RCWA) and combined boundary conditions method (CBCM) to analyze optical properties of two-dimensional periodic metamaterial grating with arbitrary shapes in microwave domain, and the adaptive spatial resolution (ASR) function is introduced to increase convergence especially for the crossed metamaterial gratings. The numerical results show that RCWA with CBCM can get the correct convergence result and distinguish the contribution of the grating lobes to the total transmission and reflection. The ASR technique improves dramatically the convergence speed of crossed grating. This method provides a more effective computational tool for the design of metamaterial grating in microwave domain.


Shelf Life and Efficacy of Diagnostic Eye Drops.
Pharmaceutical companies recommend discarding ophthalmic drugs 28 days after opening. This study shows that diagnostic eye drops have a low risk of contamination over a 7-month period in a controlled clinical setup. The diagnostic efficiency seems to be preserved over this period. The aim of this study was to evaluate the preservation period and the efficacy of ophthalmic preparations, such as 0.5% proparacaine hydrochloride, 1% tropicamide, 2.5% phenylephrine hydrochloride, and 1% cyclopentolate hydrochloride ophthalmic solution in a clinical and controlled setting. Thirty-eight primary eye care students were recruited to participate in the study. They used 25 bottles of each diagnostic drop at the Clinique Universitaire de la Vision for a 7-month period. An analysis of the bacterial contamination was repeated 10 times using both an agar plate and a nutrient broth at 0, 2, 4, 6, and 8 weeks and at 3, 4, 5, 6, and 7 months. The anesthetic, mydriatic, and cycloplegic effects were tested after 7 months of use and compared with nonopened ophthalmic bottles. During the 7-month period, 4971 drops of proparacaine, 3219 drops of tropicamide and phenylephrine, and 1896 drops of cyclopentolate were administered to the patients. A total of 226 contacts between bottles and biological tissues were reported. After the 10 inoculation sessions on the agar medium at the predetermined times, no bacterial and fungal contamination was noted. No patient reported eye infections for 2 weeks after the drop instillation. Moreover, there was no difference in the efficacy when compared with new drops. According to the results of the current study, diagnostic eye drops can be used with a low contamination risk beyond the recommendation date of 28 days up to 7 months, with the same efficacy, in a controlled clinical context.


Radical cystectomy for bladder cancer after definitive prostate cancer treatment.
To review our perioperative experience with patients presenting with high-risk bladder cancer who had undergone prior therapy for prostate cancer. With the increase in diagnosis and subsequent treatment of prostate cancer, more patients presenting with high-risk bladder cancer have undergone prior therapy for prostate cancer. Radical cystectomy in these patients can be technically challenging and may be associated with added morbidity. A retrospective review of 458 patients treated with radical cystectomy between January 1993 and January 2002 revealed 29 patients (mean age 72 years) who had received definitive treatment for prostate cancer prior to cystectomy for bladder carcinoma. The initial treatment in this cohort was radical prostatectomy or external beam radiotherapy in 12 (41%) and 17 (59%) men, respectively. Cystectomy was performed for transitional cell carcinoma in 25 (86%), small cell carcinoma in 2 (6%), and sarcoma in 2 (6%) patients. At the time of cystectomy, the mean blood loss was 1175 mL (range 275 to 3500), and the median length of hospitalization was 8 days (range 4 to 23). No intraoperative or perioperative deaths occurred in this cohort. Twenty-seven early complications were identified in 16 (55%) of 29 patients; no rectal injuries occurred. Patients with prior radiotherapy had a higher rate of extravesical bladder carcinoma (60%) than those patients treated with prior prostatectomy (33%). An orthotopic neobladder diversion was created in 5 patients (17%). Patients with bladder cancer previously treated for prostate cancer with external beam radiotherapy or radical prostatectomy have an increased risk of perioperative complications compared with patients undergoing cystectomy without prior therapy. This risk is not prohibitive, and radical cystectomy should remain the treatment of choice for high-risk bladder cancer in this population. Furthermore, orthotopic urinary diversion may be a reasonable option and should be considered in select patients.


"Migrant-friendly hospitals": a European initiative in an age of increasing mobility.
European cities are characterized by increasing numbers of foreign-born and foreign-language speaking inhabitants. The resulting cultural and linguistic diversity presents a number of challenges to health-care services. This paper describes a European initiative aimed at improving hospitals' responses to the health-care needs of migrants and ethnic minorities. We summarise the current health situation of these groups, describe how the EU initiative began and how it led to the Amsterdam declaration, and conclude by outlining current developments.


Genetic variance of Derzsy's disease strains isolated in Poland.
The aim of this study was the assessment of the genetic variance of Derzy's disease (GPV) strains isolated from cases occurring in Poland. The nucleotide and predicted aminoacid sequences of VP2 and VP3 surface proteins of the Polish GPV strains were compared with other strains previously isolated in Hungary, France, Germany, China and Taiwan. The observed genetic variance of the aminoacid sequence within the group of Polish strains was low and reached 5% of the overall analysed sequence. Considerable differences in aminoacid sequence were found in the case of Polish field GPV strains and Muscovy duck parvovirus strain MDPV FM which was also analysed in this study. The conducted investigations confirmed the presupposition that Polish GPV strains and strains previously isolated in Hungary and France share a common origin.


Single-Cycle Atomic Layer Deposition on Bulk Wood Lumber for Managing Moisture Content, Mold Growth, and Thermal Conductivity.
Wood is a universal building material. While highly versatile, many of its critical properties vary with water content (e.g., dimensionality, mechanical strength, and thermal insulation). Treatments to control the water content in wood have many technological applications. This study investigates the use of single-cycle atomic layer deposition (1cy-ALD) to apply <1 nm Al2O3, ZnO, or TiO2 coatings to various bulk lumber species (pine, cedar, and poplar) to alter their wettability, fungicidal, and thermal transport properties. Because the 1cy-ALD process only requires a single exposure to the precursors, it is potentially scalable for commodity product manufacturing. While all ALD chemistries are found to make the wood's surface hydrophobic, wood treated with TiO2 (TiCl4 + H2O) shows the greatest bulk water repellency upon full immersion in water. In situ monitoring of the chamber reaction pressure suggests that the TiCl4 + H2O chemistry follows reaction-rate-limited processing kinetics that enables deeper diffusion of the precursors into the wood's fibrous structure. Consequently, in humid or moist environments, 1cy-ALD (TiCl4 + H2O) treated lumber shows a 4 times smaller increase in thermal conductivity and improved resistance to mold growth compared to untreated lumber.


Combination of Machine Learning and Analytical Correlations for Establishing Quantitative Compliance between the Trolox Equivalent Antioxidant Capacity Values Obtained via Electron Paramagnetic Resonance and Ultraviolet-Visible Spectroscopies.
Recent interest in the antioxidant capacity of foods and beverages is based on the established medical knowledge that antioxidants play an essential role in counteracting the damaging effects of free radicals, preventing human neurodegenerative diseases, cardiovascular disorders, and even cancer. At the same time, there is no "the method" that uniquely defines the antioxidant capacity of substances; moreover, the question of interrelation between results obtained by different experimental techniques is still open. In this work, we consider the trolox equivalent antioxidant capacity (TEAC) values obtained by electron paramagnetic resonance (EPR) spectroscopy and ultraviolet-visible (UV-vis) spectroscopy using the classic objects for such studies as an example: red, rosé, and white wine samples. Based on entirely different physical principles, these two methods give values that are not so simply interrelated; this creates a demand for machine learning as a suitable tool for revealing quantitative correspondence between them. The consideration consists of an approximate correlation-based analytical model for the key argument (i.e., TEACEPR) with subsequent adjustment by machine learning-based processing utilizing the CatBoost algorithm with the usage of auxiliary chemical data, such as the total phenolic content and color index, which cannot be accurately described by analytical expressions.


Estimating hydraulic properties using a moving-model approach and multiple aquifer tests.
A new method was developed for characterizing geohydrologic columns that extended >600 m deep at sites with as many as six discrete aquifers. This method was applied at 12 sites within the Southwest Florida Water Management District. Sites typically were equipped with multiple production wells, one for each aquifer and one or more observation wells per aquifer. The average hydraulic properties of the aquifers and confining units within radii of 30 to >300 m were characterized at each site. Aquifers were pumped individually and water levels were monitored in stressed and adjacent aquifers during each pumping event. Drawdowns at a site were interpreted using a radial numerical model that extended from land surface to the base of the geohydrologic column and simulated all pumping events. Conceptually, the radial model moves between stress periods and recenters on the production well during each test. Hydraulic conductivity was assumed homogeneous and isotropic within each aquifer and confining unit. Hydraulic property estimates for all of the aquifers and confining units were consistent and reasonable because results from multiple aquifers and pumping events were analyzed simultaneously.


A feasibility study for a pragmatic randomised controlled trial comparing cast immobilisation versus no immobilisation for patients following first-time patellar dislocation.
The purpose of this feasibility study was to begin to determine the efficacy of cylinder cast immobilisation compared to no form of immobilisation for patients following first-time patellar dislocation (FTPD). Participants were patients who attended a National Health Service Accident and Emergency department following a FTPD. Patients were randomised to receive immobilisation for four weeks in a cylinder cast followed by rehabilitation, versus no immobilisation and early rehabilitation. All patients were followed-up over a three month period, assessed using the Visual analogue scale for pain, Short Form-36, the Lysholm knee score and the Modified Functional Index. Forty-one patients were approached to participate. Eight satisfied the pre-defined eligibility criteria and were randomised between the two groups. Whilst the results indicated a trend for superior short-term functional outcomes for those patients not immobilised compared to those immobilised following a FTPD, the small sample and baseline imbalances between the groups may have had a substantial influence on the results. This feasibility study has indicated that the outcome measurements adopted were appropriate to answer this research question, but the assessment of return to normal activity, recurrent instability and dislocation and cost-effectiveness over a longer follow-up period is recommended. Similarly, defining a more pragmatic eligibility criteria and recruiting from multiple centres would be recommended for the definitive trial requiring a sample of 348 patients to demonstrate a statistical significant treatment effect.


Induction and metal speciation of metallothionein in wood mice (Apodemus sylvaticus) along a metal pollution gradient.
We investigated the binding of Cd, Cu, and Zn to metallothionein (MT) and other metal-binding proteins in free-living wood mice (Apodemus sylvaticus L.) captured in four areas along a metal pollution gradient. We measured total and cytosolic Cd, Cu, and Zn concentrations in mouse liver and kidney by means of inductively coupled plasma-mass spectrometry (ICP-MS). Total (Cu, Cd, Zn)-MT levels were determined in the same tissues by means of the cadmium thiomolybdate saturation assay. Metal speciation of metalloproteins was studied by means of size-exclusion high-performance liquid chromatography-ICP-MS. Liver and kidney of wood mice from the site adjacent to the pollution source showed the highest Cd and Zn concentrations (total and cytosolic) and (Cu, Cd, Zn)-MT levels compared to the other sites farther away from the pollution source. No or only small site differences in tissue Cu concentrations were observed. Almost all the variation (85-95%) in hepatic and renal (Cu, Cd, Zn)-MT levels was explained by the total or cytosolic hepatic Zn and Cd concentration or the renal Cd concentration, respectively. An analysis of the cytosolic metal speciation showed that the Cd-MT, Cu-MT, and Zn-MT fractions in liver and kidney increased significantly with increasing cytosolic metal concentrations. Metals associated with the other cytosolic protein fractions did not increase with increasing exposure. These results illustrate the important role of MT in metal homeostasis and detoxification processes. We conclude that MT is a useful biomarker for environmental metal contamination in free-living wood mice.


Recommendations for the use of rotavirus vaccines in infants.
Rotavirus infection occurs in the majority of healthy children before five years of age, and is the most common diarrheal illness associated with hospitalization. The majority of children present with symptoms of vomiting, diarrhea and fever. As a result, rotavirus gastroenteritis is responsible for greater morbidity than other common childhood diarrheal illnesses. The highest risk of severe disease is in children younger than two years of age. It is estimated that one in 20 children will require an emergency department visit. In addition to community-acquired infections, hospital-acquired infections are also significant. There are currently two licensed rotavirus vaccines in Canada. Both vaccines are administered orally and are highly effective against severe disease and hospitalization. Large pre- and postmarketing studies have shown no increased risk of intussusception with the current rotavirus vaccines. The present statement provides information concerning the clinical disease and rotavirus vaccines in Canada.


Evidence-Based Reviews: Trends in Nephrology Nursing.
Evidence-based practice (EBP) is one of the essential components of nephrology nursing. Reviews of such evidence are important as a means to synthesize research findings into one meaningful form of data. Publication trends of evidence reviews in nephrology nursing are unknown. The purpose of this systematic review was to identify trends in publications of evidence reviews in the Nephrology Nursing Journal. Titles of all publications in the Nephrology Nursing Journal from January 2003 to September/October 2018 were reviewed. A total of 23 evidence reviews were identified and formed the basis of this systematic review. Narrative analysis and concept mapping were used to synthesize data. There was a trend toward systematic reviews of quantitative studies, as well as evidence reviews that focused on the topics of quality of life and access to health services. The need for systematic rigorous reporting is recommended for EBP, as well as future reviews on identified priority areas of research.


Influence of low back pain characteristics on the healthcare procedures prescribed by general practitioners for adult patients: ancillary analysis of the French ECOGEN study.
Non-specific low back pain is a frequent reason for consultation, yet little is known about how general practitioners manage it in France. To describe the healthcare procedures general practitioners prescribe for low back pain in France. This is an ancillary analysis of an observational, cross-sectional study (ECOGEN) conducted between November 2011 and April 2012 among 128 general practitioners. Adults younger than 65 years consulting for low back pain were included. Patient and general practitioner characteristics, consultation results (diagnosis) and healthcare procedures were collected and coded using the International Classification in Primary Care. Analyses focused on the initial or follow-up consultation, adjusting on age, gender, and socio-occupational category. Out of 11510 consultations, 845 (7.3%) were for low back pain. Of these, 776 (79.5%) resulted in a clinical examination, 634 (73.4%) in medication prescription, and 203 (23.9%) were prescribed sick leave, but imaging and specialist referral were rare. Imaging was more frequent with radiating pain (adjusted odds ratio (aOR) = 1.61; 95% CI [1.07, 2.42]), as were specialist referrals (OR = 2.92; 95% CI [1.40, 6.09]) and sick leave prescription (aOR = 1.52; 95% CI [1.10, 2.09]), but physiotherapist referral was less frequent (aOR = 0.55; 95% CI [0.38, 0.82]). Clinical examinations (aOR = 2.75; 95% CI [1.98, 3.80]), imaging (aOR = 1.61; 95% CI [1.02, 2.31]) and medication prescriptions (aOR = 2.34; 95% CI [1.65, 3.30]) were more common in initial consultations, but specialist referral (aOR = 0.16; 95% CI [0.05, 0.47]) or sick leave prescription (aOR = 0.68; 95% CI [0.48, 0.97]) were rarer. Low back pain characteristics could influence healthcare procedures more markedly than patient or general practitioner characteristics.


Midlife CAIDE dementia risk score and dementia-related brain changes up to 30 years later on magnetic resonance imaging.
CAIDE Dementia Risk Score is a validated tool for estimating 20-year dementia risk in the general population based on a midlife risk profile. To investigate the associations between CAIDE score and dementia-related brain changes up to 30 years later on magnetic resonance imaging (MRI). Participants in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study were derived from random, population-based samples surveyed in 1972, 1977, 1982, or 1987. A first re-examination was conducted in 1998, and a second re-examination in 2005-2008 (total follow-up time up to 30 years). The MRI study population included 112 individuals with MRIs from the first re-examination, and a different group of 69 individuals with MRIs from the second re-examination. MRIs from 1998 were used to determine gray matter volume, and to visually rate white matter hyperintensities (WMH) of presumed vascular origin and medial temporal lobe atrophy (MTA). MRIs from 2005-2008 were used to assess cortical thickness, gray matter and WMH volume, and to visually rate MTA. CAIDE scores were calculated for participants in both re-examinations based on midlife sociodemographic and vascular factors and additionally apolipoprotein E status. Higher midlife CAIDE score was associated with more severe WMH 20 years later: RR (95% CI) was 1.69 (1.15-2.08); and with higher WMH volume (β 0.27, p = 0.036) and higher MTA score (RR 1.91, 95% CI 1.16-2.34) up to 30 years later. CAIDE Dementia Risk Score in midlife was most consistently associated with WMH later in life. A relation with MTA was observed in individuals with longer follow-up time.


Developmental competence of equine oocytes and embryos obtained by in vitro procedures ranging from in vitro maturation and ICSI to embryo culture, cryopreservation and somatic cell nuclear transfer.
Development of assisted reproductive technologies in horses has been relatively slow compared to other domestic species, namely ruminants and pigs. The scarce availability of abattoir ovaries and the lack of interest from horse breeders and breed associations have been the main reasons for this delay. Progressively though, the technology of oocyte maturation in vitro has been established followed by the application of ICSI to achieve fertilization in vitro. Embryo culture was initially performed in vivo, in the mare oviduct or in the surrogate sheep oviduct, to achieve the highest embryo development, in the range of 18-36% of the fertilised oocytes. Subsequently, the parallel improvement of in vitro oocyte maturation conditions and embryo culture media has permitted high rates of embryo development from in vitro matured and in vitro cultured ICSI embryos, ranging from 5 to 10% in the early studies to up to 38% in the latest ones. From 2003, with the birth of the first cloned equids, the technology of somatic cell nuclear transfer has also become established due to improvement of the basic steps of embryo production in vitro, including cryopreservation. Pregnancy and foaling rates are still estimated based on a small number of in vitro produced equine embryos transferred to recipients. The largest set of data on non-surgical embryo transfer of in vitro produced embryos, from ICSI of both abattoir and in vitro-matured Ovum Pick Up (OPU) oocytes, and from somatic cell nuclear transfer, has been obtained in our laboratory. The data demonstrate that equine embryos produced by OPU and then cryopreserved can achieve up to 69% pregnancy rate with a foaling rate of 83%. These percentages are reduced to 11 and 23%, respectively, for cloned embryos. In conclusion, extensive evidence exists that in vitro matured equine oocytes can efficiently develop into viable embryos and offspring.


The experiences of violence and occupational health risks of sex workers working in brothels in ankara.
The aim of this study was to reveal and discuss occupational health risks, violence against sex workers working in brothels and their working conditions in Ankara. The study included 138 sex workers. Data were collected at face to face interviews with a questionnaire composed of 40 questions about socio-demographic features, familial characteristics, reasons for becoming a sex worker, experiences of violence and occupational health risks. Twenty-two point five percent of the women were aged 21-30 years and 39.9% were aged 31-40 years. The mean time of education was 5.9±3.5 (0-14) years. Forty-eight point five percent of the women were exposed to physical abuse and 13% of the women had been exposed to sexual abuse in their childhood. Fifty-five point eight percent of the women reported that their clients always used condoms, but 97.1% of the women noted that their clients insisted on not using a condom. Fourteen point five percent and 70.3% of the women were exposed to physical and verbal violence respectively from their clients. Ten point one percent of the women suffered sexual assault while working. Sex workers, like other people, should have human rights, all types of violence that they face should be eliminated and the social conditions they are exposed to should be improved. Sexually transmitted diseases, the most important health risk of sex workers, should be considered as occupational diseases in the new regulations.


Effective method to control catastrophic hemorrhage during redo sternotomy.
Redo sternotomy is a challenging surgical procedure performed with increasing frequency; catastrophic hemorrhage is a rare but highly lethal complication. We report our experience in treating this complication in 3 cases of 307 reoperations and propose a simple method to control catastrophic hemorrhage during sternal reentry.


[The levels of nitrites and medium molecular-weight molecules in the blood of neonatal infants with posthypoxic cardiopathy].
A hundred and four neonatal infants underwent clinical and functional studies in early neonatality. The levels of nitrites and medium molecular-weight molecules were determined in cardiologically healthy neonatal infants and children with posthypoxic cardiopathy. The magnitude of increases in biochemical parameters was found to be associated with clinical type of cardiopathy: their level significantly elevates in transient myocardial ischemia, their values achieve the maximum level in neonatal pulmonary hypertension and in the presence of functioning fetal communications.


Timing of cervical spine stabilisation and outcome in patients with rheumatoid arthritis.
One complication of rheumatoid arthritis (RA) is the involvement of the cervical spine (CS). Although prophylactic stabilisation is recommended, the timing at which this should occur is poorly defined. The aim of our study was to evaluate the course of neurological symptoms in terms of the timing of surgery. A total of 34 patients with RA and CS involvement were surgically stabilised. These patients were classified using the Ranawat (RW) score both preoperatively and at an average of 54 months post-operatively. For each patient, the presence of atlantoaxial and subaxial subluxation as well as vertical migration of the odontoid was recorded. The anterior atlantodental interval was also assessed pre- and post-operatively. Improvement was obtained in 20 patients, the clinical situation remained unchanged in three patients and three patients manifested disease progression. In terms of the RW score, the 16 patients with pre-operative RW grades I-II showed no deterioration at the post-operative follow-up, with 13 of these patients showing an improvement; the 12 patients with pre-operative RW grades IIIA-IIIB did not show any improvement of neurological symptoms at follow-up, although seven of these patients subjectively assessed the symptoms to be less severe after surgery; three other patients showed a worsening of symptoms. Our results suggest that preventive stabilisation of CS in RA leads to acceptable results, although the complications of the surgery are obvious. However, early operative treatment may delay the detrimental course of cervical myelopathy in RA.


Diversity among high-level aminoglycoside-resistant enterococci.
A total of 55 Enterococcus faecalis and 21 Enterococcus faecium non-replicate isolates were obtained from routine clinical specimens, during a 1 year period, in a tertiary care hospital in Athens, Greece. The most common isolation site was the urinary tract (44% of E. faecalis and 33% of E. faecium isolates). No vancomycin resistance was detected. Ampicillin-resistant isolates did not produce beta-lactamase. High-level gentamicin resistance was detected in 22% and 0% of E. faecalis and E. faecium isolates, respectively. The corresponding figures for high-level streptomycin resistance were 40% and 33%. The aminoglycoside-modifying enzyme gene aac(6')+aph(2") was detected by PCR in 10 of 12 high-level gentamicin-resistant E. faecalis isolates, and the ant(6)-I gene in all high-level streptomycin-resistant isolates of both species. DNA fingerprinting by PFGE grouped 31 of 55 E. faecalis isolates into 10 clusters, and 10 of 21 E. faecium isolates into two clusters, containing two to seven isolates each. Two E. faecalis PFGE types, comprising isolates expressing high-level aminoglycoside resistance, and not observed among non-high-level aminoglycoside-resistant strains, were disseminated in building A of the hospital. In contrast, high-level aminoglycoside resistance seemed to have been acquired nosocomially by a number of genotypically different E. faecium types. Molecular typing was therefore instrumental in understanding the differences in the mode of spread and acquisition of high-level aminoglycoside resistance among these two different enterococcal species.


Mechanisms of platelet activation by cultured human cancer cells and cells freshly isolated from tumor tissues.
We studied the effects on platelet function of cells isolated from freshly dissociated human tumor tissues (11 breast carcinomas, 9 colon carcinomas and 1 lymph node metastasis from melanoma) obtained at surgery as compared with cultured human tumor cells: namely, human melanoma 1402 cell line derived from a primary tumor and two lines derived from lymph node metastases (ME 7110/2 and Me 665/1) as well as a human hepatoma cell line (Hep G2). The three melanoma cell lines activated platelets by producing ADP, as evidenced by the inhibitory effect of apyrase and by the direct measurement of the agonist in the supernatants of tumor cell suspensions; this production was much greater by the cells derived from metastases than by the cells derived from the primary tumor. On the other hand, aggregation induced by Hep G2 hepatoma cells was unaffected by apyrase and was inhibited by hirudin or concanavalin A, suggesting that the cells aggregate platelets by producing thrombin, probably through tissue factor activity of the cells themselves. Cells isolated from 16 of the 21 human tumor tissues possessed a potent platelet-aggregating effect, which was not inhibited by apyrase, hirudin or concanavalin A, but was virtually abolished by the cysteine protease inhibitors iodoacetic acid or p-hydroxymercuri-phenylsulfonate. Collectively, our data demonstrate that cells isolated from freshly dissociated tumor tissues activate platelets through tumor-associated cysteine proteinases rather than by the ADP- or thrombin-dependent mechanisms characteristic of cultured human tumor cell lines.


Do Autism Spectrum and Autoimmune Disorders Share Predisposition Gene Signature Due to mTOR Signaling Pathway Controlling Expression?
Autism spectrum disorder (ASD) is characterized by uncommon genetic heterogeneity and a high heritability concurrently. Most autoimmune disorders (AID), similarly to ASD, are characterized by impressive genetic heterogeneity and heritability. We conducted gene-set analyses and revealed that 584 out of 992 genes (59%) included in a new release of the SFARI Gene database and 439 out of 871 AID-associated genes (50%) could be attributed to one of four groups: 1. FMRP (fragile X mental retardation protein) target genes, 2. mTOR signaling network genes, 3. mTOR-modulated genes, and 4. vitamin D3-sensitive genes. With the exception of FMRP targets, which are obviously associated with the direct involvement of local translation disturbance in the pathological mechanisms of ASD, the remaining categories are represented among AID genes in a very similar percentage as among ASD predisposition genes. Thus, mTOR signaling pathway genes make up 4% of ASD and 3% of AID genes, mTOR-modulated genes-31% of both ASD and AID genes, and vitamin D-sensitive genes-20% of ASD and 23% of AID genes. The network analysis revealed 3124 interactions between 528 out of 729 AID genes for the 0.7 cutoff, so the great majority (up to 67%) of AID genes are related to the mTOR signaling pathway directly or indirectly. Our present research and available published data allow us to hypothesize that both a certain part of ASD and AID comprise a connected set of disorders sharing a common aberrant pathway (mTOR signaling) rather than a vast set of different disorders. Furthermore, an immune subtype of the autism spectrum might be a specific type of autoimmune disorder with an early manifestation of a unique set of predominantly behavioral symptoms.


Matrix-Based Formulation of Heterogeneous Individual-Based Models of Infectious Diseases: Using SARS Epidemic as a Case Study.
Heterogeneities of individual attributes and behaviors play an important role in the complex process of epidemic spreading. Compared to differential equation-based system dynamical models of infectious disease transmission, individual-based epidemic models exhibit the advantage of providing a more detailed description of realities to capture heterogeneities across a population. However, the higher granularity and resolution of individual-based epidemic models comes with the cost of increased computational complexities, which result in difficulty in formulating individual-based epidemic models with mathematics. Furthermore, it requires great effort to understand and reproduce existing individual-based epidemic models presented by previous researchers. We proposed a mathematical formulation of heterogeneous individual-based epidemic models using matrices. Matrices and vectors were applied to represent individual attributes and behaviors. We derived analytical results from the matrix-based formulations of individual epidemic models, and then designed algorithms to force the computation of matrix-based individual epidemic models. Finally, we used a SARS epidemic control as a case study to verify the matrix-based formulation of heterogeneous individual-based epidemic models.


Cognitive control over unconscious cognition: flexibility and generalizability of task set influences on subsequent masked semantic priming.
Recent studies using an induction task paradigm indicated that unconscious automatic processes underlying masked semantic priming are susceptible to cognitive control influences. In this paradigm, participants first perform different induction tasks (semantic decision vs. perceptual decision), which serve to activate a corresponding task set. Thereafter, the masked prime and the target for the lexical decision task is presented. Previously, perceptual and semantic induction tasks were presented in separate blocks, and the response to the induction task was given immediately after the inducing stimulus. The present study, therefore, tested two possible boundary conditions, flexibility of cognitive control and completeness of task set execution, for the emergence of task set effects on masked semantic priming. In the first experiment, perceptual and semantic induction tasks were presented in a randomized fashion, to assess whether task set influences on masked semantic priming can occur on a trial-by-trial basis. The other two experiments tested whether task set effects on masked priming survive, when the response to the induction task is delayed. The present study yielded the same pattern of results irrespective of the variations in the induction task paradigm: When the masked prime was shortly presented after the induction task, masked semantic priming was larger subsequent to the semantic than subsequent to the perceptual induction task. The present study shows that task sets can configure unconscious processing streams rapidly on a trial-by-trial basis and demonstrates the generalizability of cognitive control effects on masked semantic priming across variations of the induction task paradigm.


Extensive marine-terminating ice sheets in Europe from 2.5 million years ago.
Geometries of Early Pleistocene [2.58 to 0.78 million years (Ma) ago] ice sheets in northwest Europe are poorly constrained but are required to improve our understanding of past ocean-atmosphere-cryosphere coupling. Ice sheets are believed to have changed in their response to orbital forcing, becoming, from about 1.2 Ma ago, volumetrically larger and longer-lived. We present a multiproxy data set for the North Sea, extending to over a kilometer below the present-day seafloor, which demonstrates spatially extensive glaciation of the basin from the earliest Pleistocene. Ice sheets repeatedly entered the North Sea, south of 60°N, in water depths of up to ~250 m from 2.53 Ma ago and subsequently grounded in the center of the basin, in deeper water, from 1.87 Ma ago. Despite lower global ice volumes, these ice sheets were near comparable in spatial extent to those of the Middle and Late Pleistocene but possibly thinner and moving over slippery (low basal resistance) beds.


Alterations in Brain Structure and Amplitude of Low-frequency after 8 weeks of Mindfulness Meditation Training in Meditation-Naïve Subjects.
Increasing neuroimaging evidence suggests that mindfulness meditation expertise is related to different functional and structural configurations of the default mode network (DMN), the salience network (SN) and the executive network at rest. However, longitudinal studies observing resting network plasticity effects in brains of novices who started to practice meditation are scarce and generally related to one dimension, such as structural or functional effects. The purpose of this study was to investigate structural and functional brain network changes (e.g. DMN) after 40 days of mindfulness meditation training in novices and set these in the context of potentially altered depression symptomatology and anxiety. We found overlapping structural and functional effects in precuneus, a posterior DMN region, where cortical thickness increased and low-frequency amplitudes (ALFF) decreased, while decreased ALFF in left precuneus/posterior cingulate cortex correlates with the reduction of (CES-D) depression scores. In conclusion, regional overlapping of structural and functional changes in precuneus may capture different components of the complex changes of mindfulness meditation training.


Health economic implications of irbesartan plus conventional antihypertensive medications versus conventional blood pressure control alone in patients with type 2 diabetes, hypertension, and renal disease in Switzerland.
The aim of this health economic modelling study was to investigate the effect of irbesartan combined with conventional antihypertensive medications compared to conventional antihypertensive therapy alone on the progression of nephropathy in patients with hypertension, type 2 diabetes and microalbuminuria in a Swiss setting. In simulated patients with hypertension and type 2 diabetes, treatment of microalbuminuria with irbesartan 300 mg daily plus conventional antihypertensive medications was compared to a control regimen (conventional medications excluding angiotensin converting enzyme inhibitors, other angiotensin-2-receptor antagonist and dihydropyridine calcium channel blockers). Progression from microalbuminuria to nephropathy, doubling of serum creatinine, ESRD, and all-cause mortality was simulated over a 25-year time horizon using a published Markov model adapted to a Swiss setting. Transition probabilities were based on the Irbesartan in Reduction of Microalbuminuria-2 Study, Irbesartan in Diabetic Nephropathy Trial and other sources. Costs and clinical outcomes were discounted at 5% annually according to Swiss guidelines, and a third party payer perspective was taken. Treatment with irbesartan was projected to improve mean life expectancy by 0.57 years compared to conventional antihypertension treatment (undiscounted 1.22 years). Irbesartan treatment was associated with cost savings of CHF 21,488 per patient over the 25-year time horizon. Sensitivity analysis showed that irbesartan therapy remained dominant to conventional antihypertension treatment over a range of plausible assumptions. Addition of irbesartan to conventional antihypertension therapy was projected to improve life expectancy and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria in a Swiss setting.