Concordance of Alzheimer's Disease-Related Biomarkers Between Intraventricular and Lumbar Cerebrospinal Fluid in Idiopathic Normal Pressure Hydrocephalus.
Alzheimer's disease cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau 181 (P-tau181) are widely used. However, concentration gradient of these biomarkers between intraventricular (V-CSF) and lumbar CSF (L-CSF) has been demonstrated in idiopathic normal pressure hydrocephalus (iNPH), potentially affecting clinical utility. Here we aim to provide conversion factors for clinical and research use between V-CSF and L-CSF. Altogether 138 iNPH patients participated. L-CSF samples were obtained prior to shunt surgery. Intraoperative V-CSF samples were obtained from 97 patients. Post-operative follow-up L- and V-CSF (shunt reservoir) samples of 41 patients were obtained 1-73 months after surgery and then after 3, 6, and 18 months. CSF concentrations of Aβ42, T-tau, and P-tau181 were analyzed using commercial ELISA assays. Preoperative L-CSF Aβ42, T-tau, and P-tau181 correlated to intraoperative V-CSF (ρ= 0.34-0.55, p < 0.001). Strong correlations were seen between postoperative L- and V-CSF for all biomarkers in every follow-up sampling point (ρs Aβ42: 0.77-0.88, T-tau: 0.91-0.94, P-tau181: 0.94-0.96, p < 0.0001). Regression equations were determined for intraoperative V- and preoperative L-CSF (Aβ42: V-CSF = 185+0.34*L-CSF, T-tau: Ln(V-CSF) = 3.11+0.49*Ln(L-CSF), P-tau181: V-CSF = 8.2+0.51*L-CSF), and for postoperative V- and L-CSF (Aβ42: V-CSF = 86.7+0.75*L-CSF, T-tau: V-CSF = 86.9+0.62*L-CSF, P-tau181: V-CSF = 2.6+0.74*L-CSF). Aβ42, T-tau, and P-tau181 correlate linearly in-between V- and L-CSF, even stronger after CSF shunt surgery. Equations presented here, provide a novel tool to use V-CSF for diagnostic and prognostic entities relying on the L-CSF concentrations and can be applicable to clinical use when L-CSF samples are not available or less invasively obtained shunt reservoir samples should be interpreted.


On speeding up stochastic simulations by parallelization of random number generation.
This paper adds to the tool kit of stochastic simulations based on a very simple idea. Applicable to both SSA and Tau-leap algorithms, it can notably reduce computational times. Stochastic simulations are based on computing sample paths based on the generation of random numbers with either exactly stipulated distribution functions as in SSA (Gillespie, 1977) or in the method of interval of quiescence (Shah et al., 1977) or distribution functions featuring approximations designed to promote efficiency (as in Tau-leap algorithms (Cao et al., 2006; Tian and Burrage, 2004; Peng et al., 2007; Gillespie, 2001; Ramkrishna et al., 2014) where a leap condition with the parameter epsilon is used). The usual strategy involves sequential computation of a large number of sample paths over a bounded time interval which is covered by a set of discrete time subintervals obtained by random number generation. The strategy here departs from the foregoing by parallelizing the generation of random subintervals for the set of sample paths until all sample paths have been computed for the stated time interval. The advantage of this procedure lies in the fact that the time for initiation of the random number generator has been notably reduced. Many examples are demonstrated from SSA as well as Tau-leap algorithms to establish that the advantage of the approach is much more than conceptual.


Correlation between the Leaflet-Annulus Index and Echocardiographic Indices in Maltese Dogs with Myxomatous Mitral Valve Disease.
Myxomatous mitral valve disease (MMVD) is the most common chronic heart valve disease, leading to left-sided cardiomegaly in dogs. The leaflet-annulus index (LAI) was originally used in humans as a predictor of mitral regurgitation (MR) after mitral valve repair surgery. This index represents the quantity and severity of MR since it is affected by annular dilation. Recently, LAI was adapted to veterinary medicine, and its usefulness as an indicator of annular dilation on 2D transthoracic echocardiography in MMVD dogs was suggested. For this study, 135 Maltese dogs were selected and divided into groups of control, B1, and B2, according to the American College of Veterinary Internal Medicine consensus statement. The following data were collected: radiographic indices including the vertebral heart score and vertebral left atrial size, echocardiographic indices including the left-atrium-to-aortic-root ratio (LA:Ao), left ventricular internal diameter at diastole, normalized for body weight, and anteroposterior length and LAI measured on right parasternal long-axis view. The results showed a significant difference in LAI between each group, becoming smaller as the disease progressed. Also, there was a significant correlation between LAI and each index, showing the strongest correlation with LA:Ao. LAI could be helpful as a new indicator used for the determination of severity and prognosis in Maltese dogs with MMVD.


Minimally invasive presacral approach for revision of an Axial Lumbar Interbody Fusion rod due to fall-related lumbosacral instability: a case report.
The purpose of this study was to describe procedural details of a minimally invasive presacral approach for revision of an L5-S1 Axial Lumbar Interbody Fusion rod. A 70-year-old Caucasian man presented to our facility with marked thoracolumbar scoliosis, osteoarthritic changes characterized by high-grade osteophytes, and significant intervertebral disc collapse and calcification. Our patient required crutches during ambulation and reported intractable axial and radicular pain. Multi-level reconstruction of L1-4 was accomplished with extreme lateral interbody fusion, although focal lumbosacral symptoms persisted due to disc space collapse at L5-S1.Lumbosacral interbody distraction and stabilization was achieved four weeks later with the Axial Lumbar Interbody Fusion System (TranS1 Inc., Wilmington, NC, USA) and rod implantation via an axial presacral approach.Despite symptom resolution following this procedure, our patient suffered a fall six weeks postoperatively with direct sacral impaction resulting in symptom recurrence and loss of L5-S1 distraction. Following seven months of unsuccessful conservative care, a revision of the Axial Lumbar Interbody Fusion rod was performed that utilized the same presacral approach and used a larger diameter implant. Minimal adhesions were encountered upon presacral re-entry. A precise operative trajectory to the base of the previously implanted rod was achieved using fluoroscopic guidance. Surgical removal of the implant was successful with minimal bone resection required. A larger diameter Axial Lumbar Interbody Fusion rod was then implanted and joint distraction was re-established. The radicular symptoms resolved following revision surgery and our patient was ambulating without assistance on post-operative day one. No adverse events were reported. The Axial Lumbar Interbody Fusion distraction rod may be revised and replaced with a larger diameter rod using the same presacral approach.


Impaired lower limb muscle mass, quality and function in end stage liver disease: A cross-sectional study.
What is the central question of this study? To what extent does musculoskeletal impairment occur (i.e., muscle mass, quality and function) in patients with end stage liver disease (ESLD) by comparison to a healthy age/sex-matched control group? What is the main finding and its importance? Muscle mass, quality and function are impaired in patients with ESLD (compared to age/sex matched controls). Importantly, greater impairments were seen in lower limb compared to arm and trunk muscle groups. These findings may suggest that there should be greater consideration of muscle health in functionally relevant lower limb muscle groups. Sarcopenia is associated with reduced quality of life and increased mortality in patients with end stage liver disease (ESLD). Historically, sarcopenia identification in ESLD utilised L3 skeletal muscle index (SMI). There are few data on muscle quality and function within lower limb muscle groups with high functional relevance. The aim of this prospective case-control study was to evaluate the quadriceps muscle in patients with ESLD. Muscle mass and quality were evaluated using MRI (quadriceps anatomical cross sectional area (ACSA), quadriceps volume index, L3 SMI, quadriceps intermuscular adipose tissue (IMAT)), mid-arm muscle circumference (MAMC) and ultrasonography (vastus lateralis (VL) thickness and quadriceps ACSA). Muscle strength/function was assessed by handgrip strength, peak quadriceps isokinetic torque and chair rise time. Thirty-nine patients with ESLD (55 years, 61% male, 48% alcoholic related liver disease (ArLD), 71% Child-Pugh B/C) and 18 age/sex-matched healthy control participants (HC) were studied. Quadriceps mass was significantly reduced in ESLD versus HC (-17%), but L3 SMI and MAMC were unchanged. Quadriceps IMAT percentage was increased in ESLD (+103%). Handgrip strength (-15%), peak isokinetic torque (-29%), and chair rise time (+56%) were impaired in ESLD. Ultrasound measures of VL thickness (r = 0.56, r = 0.57, r = 0.42) and quadriceps ACSA (r = 0.98, r = 0.86, r = 0.67) correlated to MRI quadriceps ACSA, quadriceps volume and L3 SMI, respectively. Quadriceps muscle mass, quality, and function were impaired in patients with ESLD, whereas conventional assessments of muscle (L3 SMI and MAMC) highlighted no differences between ESLD and HC. Full evaluation of lower limb muscle health is essential in ESLD in order to accurately assess sarcopenia and target future interventions.


Intracellular versus cell surface assembly of retroviral pseudotypes is determined by the cellular localization of the viral glycoprotein, its capacity to interact with Gag, and the expression of the Nef protein.
Retroviral Gag and Env glycoproteins (GPs) are expressed from distinct cellular areas and need to encounter to interact and assemble infectious particles. Retroviral particles may also incorporate GPs derived from other enveloped viruses via active or passive mechanisms, a process known as "pseudotyping." To further understand the mechanisms of pseudotyping, we have investigated the capacity of murine leukemia virus (MLV) or lentivirus core particles to recruit GPs derived from different virus families: the G protein of vesicular stomatitis virus (VSV-G), the hemagglutinin from an influenza virus, the E1E2 glycoproteins of hepatitis C virus (HCV-E1E2), and the retroviral Env glycoproteins of MLV and RD114 cat endogenous virus. The parameters that influenced the incorporation of viral GPs onto retroviral core particles were (i) the intrinsic cell localization properties of both viral GP and retroviral core proteins, (ii) the ability of the viral GP to interact with the retroviral core, and (iii) the expression of the lentiviral Nef protein. Whereas the hemagglutinin and VSV-G glycoproteins were recruited by MLV and lentivirus core proteins at the cell surface, the HCV and MLV GPs were most likely recruited in late endosomes. In addition, whereas these glycoproteins could be passively incorporated on either retrovirus type, the MLV GP was also actively recruited by MLV core proteins, which, through interactions with the cytoplasmic tail of the latter GP, induced its localization to late endosomal vesicles. Finally, the expression of Nef proteins specifically enhanced the incorporation of the retroviral GPs by increasing their localization in late endosomes.


Favorable response to immunotherapy in a pancreatic neuroendocrine tumor with temozolomide-induced high tumor mutational burden.
Neuroendocrine neoplasm of the pancreas is a rare tumor with limited treatment options. Among such tumors, treatment for pancreatic neuroendocrine tumor (PanNET) G3 is the most difficult. Temozolomide (TMZ) is commonly used to treat PanNET. However, TMZ may cause tumor gene alkylation, which induces drug resistance and rapid disease progression. Herein, we present a case of a female who was diagnosed with PanNET G3 and achieved a partial response to toripalimab, an anti-programmed cell death-ligand 1 (anti-PD-L1) monoclonal antibody, after multiple cycles of TMZ treatment. Genomic profiling revealed that compared with the patient's samples collected at baseline, the post-TMZ-treatment samples had markedly higher levels of tumor mutational burden (TMB) associated with characteristic alkylating mutational signature representing a positive correlation with favorable response to anti-PD-1 treatment. In addition, we observed a germline truncating mutation of MUTYH (W156*) that was considered to be pathogenic and potentially conferred to genomic instability. This case suggests that anti-PD-1 therapy could be a treatment option for PanNET patients with increased TMB after TMZ-based treatment.


A Metal-Organic Framework Derived Porous Cobalt Manganese Oxide Bifunctional Electrocatalyst for Hybrid Na-Air/Seawater Batteries.
Spinel-structured transition metal oxides are promising non-precious-metal electrocatalysts for oxygen electrocatalysis in rechargeable metal-air batteries. We applied porous cobalt manganese oxide (CMO) nanocubes as the cathode electrocatalyst in rechargeable seawater batteries, which are a hybrid-type Na-air battery with an open-structured cathode and a seawater catholyte. The porous CMO nanocubes were synthesized by the pyrolysis of a Prussian blue analogue, Mn3[Co(CN)6]2·nH2O, during air-annealing, which generated numerous pores between the final spinel-type CMO nanoparticles. The porous CMO electrocatalyst improved the redox reactions, such as the oxygen evolution/reduction reactions, at the cathode in the seawater batteries. The battery that used CMO displayed a voltage gap of ∼0.53 V, relatively small compared to that of the batteries employing commercial Pt/C (∼0.64 V) and Ir/C (∼0.73 V) nanoparticles and without any catalyst (∼1.05 V) at the initial cycle. This improved performance was due to the large surface area (catalytically active sites) and the high oxidation states of the randomly distributed Co and Mn cations in the CMO. Using a hard carbon anode, the Na-metal-free seawater battery exhibited a good cycle performance with an average discharge voltage of ∼2.7 V and a discharge capacity of ∼190 mAh g-1hard carbon during 100 cycles (energy efficiencies of 74-79%).


Effectiveness of the self-regulation educational program in increasing knowledge about COVID-19 in Peruvian soldiers.
To determine the effectiveness of the educational program based on self-regulation of learning in the level of knowledge about COVID-19 in the soldiers. Pre-experimental study with a pre-test and post-test design with a single group, carried out in 2020. 179 soldiers from Puno, Peru participated. Two expository-participatory sessions and a demonstrative workshop were developed. A valid (Aiken's V = 0.69) and reliable (McDonald's Omega = 0.81) questionnaire was used. The Friedman's test was used to compare the results pre and post-test. The level of knowledge about COVID-19 and in two of its dimensions changed from poor (pre-test) to regular (post-test). However, in the preventive measures dimension, it changed from poor (pre-test) to excellent (post-test). The proposed educational intervention was effective in increasing knowledge about COVID-19 in the soldiers, mainly in terms of preventive measures.


Optimization and field demonstration of the Lygus pratensis (Hemiptera: Miridae) sex pheromone.
The plant bug Lygus pratensis Linnaeus is a widely distributed polyphagous herbivore that increasingly attains outbreak population levels on cotton in northwestern China. Although the sex pheromone of L. pratensis from the United Kingdom has been identified as hexyl butyrate, (E)-2-hexenyl butyrate and (E)-4-oxo-2-hexenal, at a ratio of 100:25:24, this volatile blend does not prove attractive to Chinese field populations. In this study, we identified and optimized the sex pheromone of L. pratensis strains from northwestern China. In coupled gas chromatography and electro-antennogram detection (GC-EAD) assays, three compounds within whole-body extracts of virgin L. pratensis females elicited antennal responses: hexyl butyrate, (E)-2-hexenyl butyrate and (E)-4-oxo-2-hexenal. In field trials, a 20:1:30 ratio blend was the most attractive to L. pratensis males. Traps baited with this synthetic pheromone blend present considerable advantages over traditional sweep-net sampling for L. pratensis population monitoring. It can readily be incorporated into monitoring schemes and integrated pest management packages.


Cardiac Pressure Overload Decreases ETV1 Expression in the Left Atrium, Contributing to Atrial Electrical and Structural Remodeling.
Elevated intracardiac pressure attributable to heart failure induces electrical and structural remodeling in the left atrium (LA) that begets atrial myopathy and arrhythmias. The underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. The purpose of this study is to characterize the response of the ETV1 (ETS translocation variant 1) signaling axis in the LA during cardiac pressure overload in humans and mouse models and explore the role of ETV1 in atrial electrical and structural remodeling. We performed gene expression profiling in 265 left atrial samples from patients who underwent cardiac surgery. Comparative gene expression profiling was performed between 2 murine models of cardiac pressure overload, transverse aortic constriction banding and angiotensin II infusion, and a genetic model of Etv1 cardiomyocyte-selective knockout (Etv1f/fMlc2aCre/+). Using the Cleveland Clinic biobank of human LA specimens, we found that ETV1 expression is decreased in patients with reduced ejection fraction. Consistent with its role as an important mediator of the NRG1 (Neuregulin 1) signaling pathway and activator of rapid conduction gene programming, we identified a direct correlation between ETV1 expression level and NRG1, ERBB4, SCN5A, and GJA5 levels in human LA samples. In a similar fashion to patients with heart failure, we showed that left atrial ETV1 expression is downregulated at the RNA and protein levels in murine pressure overload models. Comparative analysis of LA RNA sequencing datasets from transverse aortic constriction and angiotensin II-treated mice showed a high Pearson correlation, reflecting a highly ordered process by which the LA undergoes electrical and structural remodeling. Cardiac pressure overload produced a consistent downregulation of ErbB4, Etv1, Scn5a, and Gja5 and upregulation of profibrotic gene programming, which includes Tgfbr1/2, Igf1, and numerous collagen genes. Etv1f/fMlc2aCre/+ mice displayed atrial conduction disease and arrhythmias. Correspondingly, the LA from Etv1f/fMlc2aCre/+ mice showed downregulation of rapid conduction genes and upregulation of profibrotic gene programming, whereas analysis of a gain-of-function ETV1 RNA sequencing dataset from neonatal rat ventricular myocytes transduced with Etv1 showed reciprocal changes. ETV1 is downregulated in the LA during cardiac pressure overload, contributing to both electrical and structural remodeling.


Acute biventricular failure as a sequela of multiple autoimmune disorders.
In this case, uncharacteristic clinical and laboratory findings led to an unanticipated diagnosis for a 24-year-old woman admitted for new-onset heart failure with features suggesting cardiac tamponade. Concomitant diagnosis of progressive mixed connective tissue disease associated with severe hypothyroidism was made. Despite early recognition (based on clinical and pathologic features) and rapid management (with glucocorticoids, thyroxine, metoprolol, lisinopril, furosemide, and milrinone), she deteriorated and died within 4 weeks.


Is enhanced platelet activation the missing link leading to increased cardiovascular risk in psoriasis?
Psoriasis is an immune mediated inflammatory skin disease associated with systemic inflammation resulting in increased risk for associated cardiovascular co-morbidities. The role of platelet activation in the pathophysiology of this condition has not been clearly studied. We undertook to study the platelet activation markers in psoriasis, as compared to controls and to identify its association with disease severity in psoriasis. Sixty-two patients with psoriasis and 62 age and gender matched healthy controls were enrolled in this cross-sectional study. The severity of the disease was assessed using the psoriasis area severity index (PASI) scoring. The platelet indices [mean platelet volume (MPV) and platelet distribution width (PDW)] were estimated by an automated haematological laser optical analyzer. Plasma soluble P-selectin and platelet derived microparticle (PDMP) concentrations, serum high sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 concentrations were estimated in all study participants. Platelet aggregation was assessed using adenosine diphosphate (ADP) as aggregating agent. We observed that there was significantly higher platelet indices (MPV and PDW) in patients with psoriasis, when compared to controls. Plasma soluble P-selectin concentrations, PDMP and platelet aggregation were significantly elevated in patients with psoriasis, as compared to controls. We also found significantly higher concentrations of hs-CRP and IL-6 in patients with psoriasis, as compared to controls. Platelet activation and systemic inflammation markers correlated positively with PASI, except PDW. We also observed significant positive correlation between platelet activation and systemic inflammation in psoriasis. Significant platelet activation and systemic inflammation were observed in patients with psoriasis, especially when associated with severe disease. The increased platelet activation might be the missing link between the persistent inflammation and the development of atherosclerotic plaque leading onto cardiovascular co-morbidities seen associated with psoriasis.


[Total reconstruction of the lower lip: Lip suspension technique by double nasolabial rigging and review of the literature].
Total lower lip defect is rare and its reconstruction difficult. The challenges are both aesthetic and functional. Suspension of the lower lip is essential for restoring oral competence. We report an original and simple technique of suspension by double nasolabial rigging. Two upper base orbitonasolabial flaps, extended over several centimeters below the lip commissures are raised. The epidermis is completely removed. Then, the flaps are tunneled under the skin and fixed to the reconstructed lower lip in order to provide it with effective suspension to the maxillary. In our experience, we used the nasolabial rigging associated with a total reconstruction of the lower lip for three patients. Lip continence is effective in the long term. The review of literature shows that the use of conventional locoregional flaps restores a good labial competence but is limited to subtotal lower lip defect. Distant pedicled flaps or free flaps made without suspension of the lower lip don't restore the labial competence. Several procedures to suspend the lower lip with strips of fascia lata or tendon of palmaris longus, associated or not with a free flap, seem to provide satisfactory oral competence. All these techniques are poorly standardized and technically difficult. The technique of the double nasolabial rigging that we describe seems to be an effective and interesting alternative by its simplicity, its reproducibility and its adaptability. It allows to obtain a perfectly fixed posterior plane, able to receive any reconstruction of the lower lip.


Comment on "The promise of microfluidic artificial lungs" by J. A. Potkay, Lab Chip, 2014, 14, 4122-4138.
This comment on an article that appeared in this journal (Potkay, Lab Chip, 2014, 14, 4122-4138) presents an alternative view on the feasibility and clinical application of current microfluidic artificial lungs.


Regeneration potential of bone marrow derived mesenchymal stem cells and platelet rich plasma (PRP) on irradiation-induced damage of submandibular salivary gland in albino rats.
Radiation-induced damage to salivary glands (SG) is a consequence of radiotherapy for head and neck cancers. Recovery of the irradiated SG has been studied using various regenerative approaches. This study aims to compare the regenerative potentials of platelet-rich plasma (PRP) and bone marrow mononuclear cells (BMMCs) on irradiated rat submandibular salivary glands (SMD). 32 healthy male albino rats were irradiated with a single dose of 6 Gy then classified into four groups. Group A received no treatment while the other 3 groups were injected 24 h post-radiation with a single dose of either; BMMCs (Group B), PRP (Group C), or BMMCs suspended in PRP (Group D). SMD regeneration was assessed in terms of histological changes and TGF- β1 gene expression. The results showed that compared to the untreated group all groups showed successful regeneration with group D showing the best results. A statistically significant increase in the surface area of acini and TGF- β1 gene expression was observed in group D, followed by group C, then B. Our results prove that using PRP and BMMCs could be promising in decreasing irradiation side effects on SG. Moreover, combining PRP and BMMCs gives better effects compared to each therapy alone.


A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study.
Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing.


Body mass index and efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes.
The efficacy and safety of ticagrelor vs prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unstudied. We assessed the efficacy and safety of ticagrelor vs prasugrel in patients with ACS according to BMI. Patients (n=3987) were grouped into 3 categories: normal weight (BMI <25kg/m2; n=1084), overweight (BMI ≥ 25 to <30kg/m2; n=1890), and obesity (BMI ≥ 30kg/m2; n=1013). The primary efficacy endpoint was the 1 year incidence of all-cause death, myocardial infarction, or stroke. The secondary safety endpoint was the 1 year incidence of Bleeding Academic Research Consortium type 3 to 5 bleeding. The primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the normal weight group (11.7% vs 7.5%; HR, 1.62; 95%CI, 1.09-2.42; P=.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the overweight group (8.3% vs 6.2%; HR, 1.36; 95%CI, 0.97-1.91; P=.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the obesity group (8.6% vs 7.3%; HR, 1.18; 95%CI, 0.76-1.84; P=.451). The 1-year incidence of bleeding events did not differ between ticagrelor and prasugrel in patients with normal weight (6.5% vs 6.6%; P=.990), overweight (5.6% vs 5.0%; P=.566) or obesity (4.4% vs 2.8%; P=.219). There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (Pint=.578) or secondary endpoint (Pint=.596). In patients with ACS, BMI did not significantly impact the treatment effect of ticagrelor vs prasugrel in terms of efficacy or safety. NCT01944800.


Possible relationship between micronucleated and binucleated cells induced by cisplatin in cultured CHO cells.
Chinese hamster ovary (CHO) cells were treated with a single dose (10 micrograms/ml) of cis-diamminodichloroplatinum (II) (cisplatin) for 1 h and the effect of the drug on the kinetics of proliferation of the cultures was studied. It was found that the drug produces a delay in the proliferation rates of the treated cultures. The induction of micronuclei and binucleated cells (BC) at different times after treatment have also been studied, and the ability of these cells to undergo DNA synthesis (measured as the ability to incorporate [3H]thymidine) is shown. It was also found that cisplatin induced a particular type of BC that contains one or more micronuclei rather than a pure population of BC. The results obtained show a possible relationship between micronuclei and BC. The possibility that some of the micronucleated cells evolve in subsequent cell divisions to BC with micronuclei is suggested.


Exploring the degrees of distortion in simulated human bite marks.
The properties of the skin and the posture of the body during photographic recording are factors that cause distortion in the bite mark injury. This study aimed to explore the degree of distortion between a 'touch mark' (method 1) and a 'bite mark' (method 2) on the left upper arm at three different positions (arm relaxed; arm flexed in two different positions). A pair of dental casts with biting edges coated in ink was used to create a mark in 30 subjects (6 ♂, 24 ♀) aged 20-50 years old. Photographs were taken using a Nikon DX digital camera (D5000). The mesiodistal widths and angle of rotations of both upper right central incisor and lower right central incisor and the inter-canine distances were analysed and compared with the true measurements using Adobe Photoshop CC 2017. Statistical analysis was carried out using SPSS Statistics 22 applying a 2 (mark type) × 3 (position) repeated measures ANOVA. For all measures studied, there was a statistically significant difference between mark types and positions. In the case of bite marks, a great degree of distortion was detected, and this increased further when changing the position of the arm. The findings demonstrated that skin properties and posture influence distortion. This could lead to inaccurate measurements and misleading pattern interpretation of bite mark injuries.


Genomic evaluation with multibreed and crossbred data.
Several types of multibreed genomic evaluation are in use. These include evaluation of crossbreds based on purebred SNP effects, joint evaluation of all purebreds and crossbreds with a single additive effect, and treating each purebred and crossbred group as a separate trait. Additionally, putative quantitative trait nucleotides can be exploited to increase the accuracy of prediction. Existing studies indicate that the prediction of crossbreds based on purebred data has low accuracy, that a joint evaluation can potentially provide accurate evaluations for crossbreds but could lower accuracy for purebreds compared with single-breed evaluations, and that the use of putative quantitative trait nucleotides only marginally increases the accuracy. One hypothesis is that genomic selection is based on estimation of clusters of independent chromosome segments. Subsequently, predicting a particular group type would require a reference population of the same type, and crosses with same breed percentage but different type (F1 vs. F2) would, at best, use separate reference populations. The genomic selection of multibreed population is still an active research topic.


Patients with Non-response to Neoadjuvant Chemoradiation for Esophageal Cancer Have No Survival Advantage over Patients Undergoing Primary Esophagectomy.
Survival for patients with locally advanced esophageal cancer remains dismal. Non-response to neoadjuvant chemoradiation (nCRT) portends worse survival. We hypothesized that patients undergoing up-front esophagectomy may have better survival than those who do not respond to nCRT. We identified all patients undergoing esophagectomy with a pathologic stage of II or greater at our institution between 1994 and 2015 and separated them into two groups: those who received nCRT and those undergoing up-front esophagectomy. The neoadjuvant group was further separated into patients downstaged to pathologic stage 0 or I (responders) and patients with either the same or higher pathologic stage after nCRT, or with pathologic stage II disease or greater (non-responders). Overall survival was compared between groups using Kaplan-Meier statistics. Covariate-adjusted Cox modeling was used to estimate hazard ratios (HR) for mortality associated with non-response. Overall, 287 patients met inclusion criteria. Fifty-nine percent of the responders had pathologic complete response (pCR). The majority of non-responders and primary esophagectomy patients had stage II or III disease (94%). Median survival was 58.3 months in responders, 23.9 months in non-responders, and 29.1 months in primary esophagectomy patients (p < 0.01). The HR for mortality associated with non-response was 1.82 compared to response to nCRT (p < 0.01) and 1.09 compared to primary esophagectomy (p = 0.71). In patients with esophageal cancer who do not respond to nCRT, neoadjuvant therapy may represent a toxic and costly treatment modality that does not improve survival and may delay potentially curative resection. Further research is needed to identify potential non-responders with advanced resectable disease and allow individual tailoring of pre-surgical decision-making.


Effects of probiotic administration on overweight or obese children: a meta-analysis and systematic review.
This paper aimed to examine the effects of probiotics on eight factors in overweight or obese children by meta-analysis, namely, body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), adiponectin, leptin and tumor necrosis factor-α (TNF-α) and summarize the mechanisms of action of probiotics based on the existing researches. Six databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed and CNKI) were searched until March 2023. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model or random effect model to observe the effects of probiotic administration on the included indicators. Four publications with a total of 206 overweight or obesity children were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HDL-C (MD, 0.06; 95% CI 0.03, 0.09; P = 0.0001), LDL-C (MD, - 0.06; 95% CI - 0.12, - 0.00; P = 0.04), adiponectin (MD, 1.39; 95% CI 1.19, 1.59; P < 0.00001), leptin (MD, - 2.72; 95% CI - 2.9, - 2.54; P < 0.00001) and TNF-α (MD, - 4.91; 95% CI - 7.15, - 2.67; P < 0.0001) compared to those in the placebo group. Still, for BMI, the palcebo group seemed to be better than the probiotic group (MD, 0.85; 95% CI 0.04, 1.66; P = 0.04). TC (MD, - 0.05; 95% CI - 0.12, 0.02; P = 0.14) and TG (MD, - 0.16; 95% CI - 0.36, 0.05; P = 0.14) were not different between two groups. This review drew that probiotics might act as a role in regulating HDL-C, LDL-C, adiponectin, leptin and TNF-α in overweight or obesity children. Additionally, our systematic review yielded that probiotics might regulate lipid metabolism and improve obese associated symptoms by some paths. This meta-analysis has been registered at PROSPERO with ID: CRD42023408359.


Long-term prognosis of giant coronary aneurysm in Kawasaki disease: an angiographic study.
The incidence of coronary obstruction subsequent to giant coronary aneurysm in Kawasaki disease was studied. In 20 cases, aneurysms with a maximal diameter greater than 8 mm were identified by coronary angiography 2 to 120 months (mean 16.9 months) after onset. There were 25 giant aneurysms among these 20 patients, all of whom underwent coronary angiography between 12 and 134 months (mean 31.7 months) after initial examination. Coronary obstruction occurred in six cases (30.0%), all within 4 years of onset of disease. There were five obstructive aneurysms in the right coronary artery (5/12; 41.7%) and two in the left coronary artery (2/13; 15.4%). One of these patients developed symptomatic myocardial infarction. Two had abnormal electrocardiographic findings suggesting myocardial infarction. In five cases, persistent perfusion defects were found by myocardial imaging. On the other hand, in two patients giant aneurysms persisted without obstructive changes for greater than 10 years. In both cases the aneurysm was in the left coronary artery and obstruction of the right coronary artery was found at initial angiography. These results seem to indicate the limited efficacy of antiplatelet therapy for giant coronary aneurysms in Kawasaki disease and that giant aneurysms are likely to progress to become obstructive within a few years even if antiplatelet therapy is given. Other forms of treatment, including surgery, should therefore be considered in such patients.


Echocardiography-Based Hemodynamic Monitoring Use on Inpatients Listed for Heart Transplantation Under 2018 Allocation Policy in United States.
One notable change to the 2018 United Network for Organ Sharing listing criteria was to allow for the use of noninvasive hemodynamic monitoring for inpatients listed as status 3 for heart transplantation. We wanted to explore the feasibility of performing daily focused echocardiograms in place of invasive monitoring in this population. On retrospective chart review of inpatients listed for transplantation at our institution, 8 patients in the invasive monitoring group listed as status 1A (October 2016 to October 2018) and 9 patients in the echocardiographic group listed as status 3 (October 2018 to February 2020) were identified. There were no significant differences between the 2 cohorts in the average measured/estimated right atrial, pulmonary artery systolic, and wedge pressures, although the echo cohort had lower cardiac index (P = .001). There were 2 patients with positive blood cultures treated with Swan exchange in Swan cohort and a total of 14 Swan exchanges. There were no infections in the noninvasive group. We present our experience with the use of noninvasive daily hemodynamic assessment using focused echocardiograms to manage patients undergoing heart transplantation listing as status 3 under the new United Network for Organ Sharing allocation system. This approach appears safe and feasible; however, it requires validation in larger cohorts.


A turn-on fluorescent probe based on ESIPT and AIEE mechanisms for the detection of butyrylcholinesterase activity in living cells and in non-alcoholic fatty liver of zebrafish.
Butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are two important cholinesterase enzymes in human metabolism which are closely related to various diseases of the liver. BChE and AChE are difficult to be distinguished due to their similarity in biochemical properties. Therefore, developing BChE-specific probes with high sensitivity and low background reading is desirable for the relevant biological applications. Herein, we reported the design and synthesis of a fluorescent probe HBT-BChE for biological detection and imaging of BChE. The probe is triggered by BChE-mediated hydrolysis, releasing a fluorophore that holds AIEE and ESIPT properties with large Stokes shift (>100 nm), rendering the probe features of low background interference and high sensitivity. The probe can also distinguish BChE from AChE with a low detection limit of 7.540 × 10-4 U/mL. Further in vitro studies have shown the ability of HBT-BChE to detect intracellular BChE activity, as well as to evaluate the efficiency of the BChE inhibitor. More importantly, the in vivo studies of imaging the BChE activity level in liver tissues using zebrafish as the model animal demonstrated the potential of HBT-BChE as a powerful tool for non-alcoholic fatty liver disease.


[Treatment of a partial avascular necrosis of a metacarpal head (Morbus Mauclaire Dieterich's Disease) utilizing the ostechondral autograft transfer system (OATS) technique].
The OATS (osteochondral autograft transfer system) is a standardized technique for the treatment of aseptic osteonecrosis of the knee and ankle. We show the first use and successful course of the OAT System for the treatment of a partial aseptic necrosis of a metacarpal head.


Association of hypoxia-inducible factor-1 expression with histology in epithelial ovarian tumors: a quantitative analysis of HIF-1.
Hypoxia-inducible factor-1 (HIF-1) is an essential transcription factor that mediates cellular and systemic homeostatic responses to reduced oxygen availability in mammals. So far, using immunohistochemistry we have analyzed the association of HIF-1alpha expression with histological type among epithelial ovarian tumors. In the present study, quantitative analyses of activated HIF-1 level in the nucleus and of accumulated HIF-1alpha level in the cytoplasm were performed to clarify whether or not the hypoxic state would be correlated to histology, malignancy, and tumor size in epithelial ovarian tumors. HIF-1 level in the nucleus was analyzed using DNA binding assay, and HIF-1alpha level in the cytoplasm was measured by ELISA for a total of 36 epithelial ovarian tumors as follows: 5 serous adenocarcinomas (SEAs), 7 clear cell adenocarcinomas (CLAs), 7 endometrioid adenocarcinomas (ENAs), 4 mucinous adenocarcinomas (MUAs), 2 mucinous borderline tumors (MBTs), and 11 mucinous adenomas. HIF-1 level (mg/ml) in the nucleus and HIF-1alpha level (mg/ml) in the cytoplasm were on average 0.116 and 0.178 for SEAs, 0.328 and 0.306 for CLAs, 0.171 and 0.305 for ENAs, 0.097 and 0.176 for MUAs, 0.224 and 0.180 for mucinous borderline tumors, 0.152 and 0.154 for mucinous adenomas. CLAs showed the highest levels for both of HIF-1 and HIF-1alpha, while MUAs showed the lowest levels of both. Mucinous adenomas were higher in HIF-1 than MUAs. Hypoxic state was considered to be closely related to histological type of epithelial ovarian tumors, suggesting that CLAs may be most hypoxic. In the comparison of mucinous tumors, malignancies would not always become most hypoxic. Tumor size may not be strongly associated with hypoxic state.


Platelet protection by low-dose aprotinin in cardiopulmonary bypass: electron microscopic study.
To evaluate the effect of low-dose aprotinin during cardiopulmonary bypass on platelet function and clinical hemostasis, 30 patients undergoing various cardiopulmonary bypass procedures employing bubble oxygenators were randomized to receive either low-dose aprotinin (2 x 10(6) KIU in the cardiopulmonary bypass priming solution, 15 patients [group A]) or placebo (15 patients [group B]). Blood samples were collected before and after cardiopulmonary bypass to assess platelet count and aggregation on extracellular matrix, which was studied by a scanning electron microscope. On a scale of 1 to 4 preoperative mean platelet aggregation grades were similar in both groups (3.8 +/- 0.5 and 3.5 +/- 0.5 for groups A and B, respectively). Postoperatively, platelet aggregation on extracellular matrix decreased slightly in group A (2.8 +/- 1.3; p < 0.01) and significantly in group B (1.3 +/- 0.5; p < 0.001). Eleven of the 15 patients in group A remained in aggregation grade 3 or 4 compared with none of the group B patients. Platelet count was similar in both groups preoperatively and postoperatively. Total 24-hour postoperative bleeding and blood requirement were lower in the aprotinin group (487 +/- 121 mL and 2.3 +/- 1.0 units) than in the placebo group (752 +/- 404 mL and 6.8 +/- 5.1 units; p < 0.01). These results show that the use of low-dose aprotinin during cardiopulmonary bypass provides improved postoperative hemostasis, which might be related to the protection of the platelet aggregating capacity.


Analysis of imaging axes significance in motion artifact suppression technique (MAST): MRI of turbulent flow and motion.
Recently, a new technique has been demonstrated which effectively refocusses the dephasing effects of spins moving during application of MR imaging gradients. This paper presents an analysis of imaging axes significance in spin dephasing for motion occurring along the slice select, read and phase-encoding directions. A flow phantom under constant flow conditions in all experiments was used to provide complete spin dephasing when "traditional" imaging gradients were used. The MAST technique was used to refocus along various combinations of imaging axes, and variable number of terms from the Taylor expansion of motion along them. Results indicate that motion along any imaging axis can be refocussed effectively when MAST gradients are used along only the slice select and read axis.


The effect of drug consultation center guidance on contraceptive use among women using isotretinoin: a randomized, controlled study.
Women of reproductive age treated with isotretinoin are required to use two forms of contraceptives, yet adherence to the recommendations is limited. Our objective was to determine if an active intervention by a drug consultation center (DCC) will increase contraceptive use among women taking isotretinoin. In a randomized, controlled study, women of reproductive age who called the DCC seeking advice regarding isotretinoin were randomly assigned to an intervention group (information by phone during initial interview, by mailed written form, and by text messages sent to their cellular phones) and a control group (information given once). A follow-up call was made to all women 3 months after the first interview. One hundred eight women (50 in the intervention group and 58 control) were enrolled. Most women do not adhere to the recommended contraceptive use. After 3 months, 50% of the study group and 40% of the control group were using a contraceptive (p = 0.41), and only 2 women in each group used two methods of contraception. Strategies to increase adherence to contraceptive use among women treated with isotretinoin are needed.


Long-Term Epidemiology and Evolution of Swine Influenza Viruses, Vietnam.
Influenza A viruses are a One Health threat because they can spill over between host populations, including among humans, swine, and birds. Surveillance of swine influenza virus in Hanoi, Vietnam, during 2013-2019 revealed gene pool enrichment from imported swine from Asia and North America and showed long-term maintenance, persistence, and reassortment of virus lineages. Genome sequencing showed continuous enrichment of H1 and H3 diversity through repeat introduction of human virus variants and swine influenza viruses endemic in other countries. In particular, the North American H1-δ1a strain, which has a triple-reassortant backbone that potentially results in increased human adaptation, emerged as a virus that could pose a zoonotic threat. Co-circulation of H1-δ1a viruses with other swine influenza virus genotypes raises concerns for both human and animal health.


A new approach to the synthesis of chiral blocks for cyclopentanoids.
A microreview is presented of the development by the authors of the original preparation of enantiomerically pure cyclopentane blocks from the racemic [2+2]-cycloadducts of 1,3-cyclopentadiene and its derivatives with dichloroketene.


The pharmacokinetics of volatile anesthetic agent elimination: a theoretical study.
The theoretical groundwork for a rate constant formulation of inhaled anesthetic elimination kinetics is discussed. In an effort to simulate recent experimental results a linear flow-limited five-compartment model was used comprising lung, vessel-rich tissue, muscle, nonvisceral fat, and an additional compartment, marrow-visceral fat whose functional existence recently has been experimentally demonstrated. Hypothetical but plausible parameters for the marrow-visceral fat compartment were used. The theoretically predicted values were in good agreement with experimental results suggesting that this model is appropriate for the elimination kinetics of agents that are not metabolized to any significant degree. Simple approximate expressions for the rate constants were also derived and were in reasonable agreement with experimental results. The model was also employed to clarify the effect of anesthetic duration on subsequent elimination kinetics.


Oral health status and dental care behaviours of head and neck cancer patients: a cross-sectional study in an Austrian tertiary hospital.
This study aimed to assess the oral health status and dental care behaviours of patients treated for head and neck squamous cell carcinoma (HNSCC) in an Austrian tertiary hospital. Dental care behaviours, oral hygiene level, caries, and periodontal parameters were assessed in 48 patients treated for HNSCC >6 months ago. Only 52 % requested a dental check-up after HNSCC diagnosis and prior to treatment, and of those, 80 % received some type of dental treatment. At time-point of clinical examination, 69 % of the patients had consulted a dentist within the last year, but 88 % still needed dental treatment; 75 % had at least one tooth with caries and 78 % had moderate to severe periodontitis. Although it was recommended, only half of the patients did consult a dentist prior to HNSCC treatment and oral health appeared, in general, low prioritized. About 90 % of the current group of head and neck squamous cell carcinoma cancer patients presented large treatment needs, both in regard with caries and periodontal disease, about 20 months after cancer treatment.


Paediatric Trauma Presentations in a Teaching Hospital in Lagos, Nigeria: Epidemiology and Predictor of Mortality.
Paediatric trauma remains a major health challenge worldwide. It remains a major reason for hospitalization among children and adolescents around the world, with resultant death or disability. This study was aimed to determine the epidemiology, pattern and outcomes of paediatric injuries presenting at a teaching hospital in Lagos, South-west Nigeria. This was a prospective observational hospital based study conducted on all paediatric trauma patients below 18 years, who presented at the accident and emergency room of the Lagos University Teaching Hospital (LUTH) over a period of thirteen months. Data analysis was done with Stata v13 (StataCorp. Texas. USA). A total of 154 patients sustained 250 documented injuries. The mean age was 6.8 ± 4.6 years. Male to female ratio was 1.5:1. Children aged 8 years were mostly affected. There was significant statistical association between age of child at injury and the place of injury. (p = 0.021) Most injuries (51.3%) occurred at home followed by the road. Falls accounted for 72 cases (46.8%). Traumatic brain injury was the most common injury sustained. Injuries at home peaked at 5pm and extended to 7pm while injuries from road traffic accidents peaked at two periods; between 7am and 8am and 4pm. Paediatric trauma score predicted death accurately. The crude mortality rate was 5.8%. Paediatric trauma scourge is still a health concern. School age children are mostly affected by trauma. Falls were the most common cause of trauma in children and most falls occurred in the home environment. Injuries from road traffic accidents accounted for majority of deaths. The paediatric trauma score predicts mortality in injured children and should be routinely used.


A comparative study of anatomical single-bundle anterior cruciate ligament reconstruction using femoral offset aimer versus freehand technique for femoral tunnel preparation.
ACL reconstruction is one of the commonest orthopaedic procedures performed. There has been a shift in techniques from single bundle to double bundle to anatomic single-bundle reconstruction and also from transtibial to anteromedial method. Anteromedial technique results in more anatomic femoral tunnel with graft positioned at the native insertion site. The tunnel position is crucial for better outcome after ACL reconstruction. To compare the femoral tunnel position made by anatomic single-bundle ACL reconstruction using femoral offset aimer device versus freehand drilling with 3D computed tomography. A prospective case series involving 60 patients with ACL tear who underwent anteromedial single-bundle ACL reconstruction. Computed tomography scans were performed on 60 knees that underwent single-bundle anteromedial ACL reconstruction with 30 cases involving femoral drilling through aimer device and another 30 cases involving freehand drilling of the tunnel. Three-dimensional models were created, and the data were analysed according to the co-ordinate axes method. Femoral tunnel position was measured in proximal-to-distal and posterior-to-anterior directions. Data from both the groups were compared with each other and already published reference data on anatomical tunnel position. In the aimer group, the femoral tunnel centre on the medial wall of lateral femoral condyle was located at 35 ± 9% in the posterior-to-anterior direction and at 30 ± 12% in the proximal-to-distal direction. In the freehand group, tunnel was placed at 37 ± 10% in posterior-to-anterior and 28 ± 7% in proximal-to-distal directions. There was no significant difference in tunnel position in both the groups. This study shows there is no significant difference between both the drilling techniques of femoral tunnel, i.e. freehand drilling and drilling with aimer device. Also, it reiterates the efficacy and utility of computed tomography and three-dimensional reconstruction in the analysis of femoral tunnel in ACL reconstruction.


"Underwater" EMR without submucosal injection for large sessile colorectal polyps (with video).
Submucosal injection is widely performed before EMR of large sessile colorectal polyps to facilitate resection and decrease perforation risk. We developed a novel method of water immersion ("underwater") EMR (UEMR) that eliminates submucosal injection. To evaluate the feasibility and outcomes of UEMR without submucosal injection for large sessile colorectal polyps. Prospective, observational study. Single, tertiary-care referral center. The standardized EMR technique involves full water immersion for the entire procedure and piecemeal resection with a 15-mm "duck bill" snare. Complete resection, bleeding, perforation, postpolypectomy syndrome, residual or recurrence adenoma. Sixty patients with 62 large sessile colorectal polyps underwent UEMR. The mean/median polyp size was 34/30 mm, and the mean/median resection time was 21/18 minutes. Histology revealed the following: tubular adenoma (n = 22), tubulovillous adenoma (n = 19), villous adenoma (n = 4), serrated adenoma (n = 11), and high-grade dysplasia/carcinoma in situ (n = 6). The mean/median interval until a follow-up colonoscopy in 54 patients (90%) was 20.4/15.2 weeks. One of 54 patients (2%) had an adenoma smaller than 5 mm outside of the postresection scar, consistent with a residual lesion missed on index UEMR. There was no perforation or postpolypectomy syndrome. Delayed bleeding occurred in 3 patients and was managed conservatively. Limited follow-up; single-center, single-endoscopist, uncontrolled study. The underwater resection technique enables complete removal of large sessile colorectal polyps without submucosal injection. The technique was safe in a large patient cohort, and the early recurrence rate appears low. Use of a water interface for UEMR has potential advantages that deserve further study.


Citrate levels in fresh tomato juice: a possible dietary alternative to traditional citrate supplementation in stone-forming patients.
To detect citrate levels in fresh tomato juice, to reveal whether it can be studied for prevention of recurrent hypocitraturic nephrolithiasis. Juices of tomato, orange, lemon, and mandarin were extracted and blended with a hand blender, and 10 samples of 100 mL were taken from each. Citrate, oxalate, calcium, phosphorus, magnesium, sodium, potassium, chloride, and pH levels were examined in these. The same variables were re-evaluated after the samples were stored at +4 degrees C for 1 week. In fresh tomato juice, higher citrate and magnesium levels as well as lower sodium and oxalate levels were detected as compared with the other juices. No differences were observed with regard to all variables among fresh orange, lemon, and mandarin juices. The level of citrate in the fresh tomato juice was higher at a statistically significant level than that in tomato juice that was stored for 1 week. The amount of oxalate increased in stored tomato juice. Fresh tomato juice is considered a rich source of citrate. Furthermore, a high level of magnesium and a low level of sodium and oxalate content were detected in fresh tomato juice, the usability of which in recurrent hypocitraturic nephrolithiasis can be investigated in clinical studies.


Fast sequential determination of antimony and lead in pewter alloys using high-resolution continuum source flame atomic absorption spectrometry.
A simple method has been developed to determine antimony and lead in pewter alloy cups produced in Brazil, using fast sequential determination by high-resolution continuum source flame atomic absorption spectrometry. The samples were dissolved in HCl and H(2)O(2), employing a cold finger system in order to avoid analyte losses. The main resonance line of lead at 217.001 nm and a secondary line of antimony at 212.739 nm were used. The limits of detection for lead and antimony were 0.02 and 5.7 mg L(-1), respectively. The trueness of the method was established by recovery tests and comparing the results obtained by the proposed method with those obtained by inductively coupled plasma optical emission spectrometry. The results were compared using a student's t-test and there was no significant difference at a 95% confidence interval. With the developed methods, it was possible to determine accurately antimony and lead in pewter samples. The lead concentration found in the analysed samples was around 1 mg g(-1), which means that they are not lead free; however, the content was below the maximum allowed level of 5 mg g(-1). The antimony content, which was found to be between 40 and 46 mg g(-1), is actually of greater concern, as antimony is known to be potentially toxic already at very low concentrations, although there is no legislation yet for this element.


A new population-based reference curve for symphysis-fundus height.
To present a new gestational-age-specific percentile curve for symphysis-fundus (SF) height and to determine the effects of maternal and fetal covariates. A population-based register study. Antenatal clinics in Västra Götaland County, Sweden, between 2005 and 2010. A total of 42 018 women with ultrasound-dated singleton pregnancies who delivered at Sahlgrenska University Hospital. Measurement of SF height. A non-linear regression of SF height on day of pregnancy was used to construct a reference chart for the median and other percentiles of SF height. The new reference curve for SF height showed almost linear growth until term. The median value was considerably larger at each gestational age compared with the curves for SF height used in Norway and Denmark. Compared with the curve currently used in Sweden, higher median values were observed only at gestational ages >34 weeks, accompanied by an upward shift in all percentiles. The only notably influential covariates were maternal pre-pregnancy weight and height. The new reference curve for SF height shows a pattern that is different from the Scandinavian reference curves of older origin, reflecting changes in the pregnant population, as well as methodological differences. The new curve can be adjusted for maternal and fetal covariates to suit individual pregnancies.


ML323, a USP1 inhibitor triggers cell cycle arrest, apoptosis and autophagy in esophageal squamous cell carcinoma cells.
Esophageal squamous cell carcinoma (ESCC) is a common digestive cancer with high mortality rate due to late diagnosis and drug resistance. It is important to identify new molecular target and develop new anticancer strategy. ML323 is a novel USP1 inhibitor and exhibits anticancer activity against several cancers. Herein, we investigated whether ML323 has some cytotoxity effect on ESCC cells and explored the underlying mechanisms. Results revealed that ML323 impeded esophageal cancer cell viability and colony formation. Meanwhile, ML323 blocked cells at G0/G1 phase concomitant with the reduced protein level of c-Myc, cyclin D1, CDK4 and CDK6. ML323 treatment also triggered DNA damage and active p53. Then, ML323 induced apoptosis by p53-Noxa. Additionally, it stimulated protective autophagy. Co-treatment with CQ or BafA1, two classical autophagy inhibitors, enhanced the cytotoxity of ML323. These findings suggested that USP1 inhibitor (ML323) could be used as a viable anti-ESCC approach.


Effects of fresh bone marrow mononuclear cell therapy in rat model of retinopathy of prematurity.
Retinopathy of prematurity (ROP) is a vasoproliferative disease that alters retinal vascular patterns in preterm neonates with immature retinal vasculature. This study was conducted to investigate the effects of cell therapy by bone marrow mononuclear cells (BMMNC) on neurological and vascular damages in a rat model of ROP. Ten newborn Wistar rats were divided randomly into the control and the oxygen-induced retinopathy (OIR) groups. Animals in the OIR group were incubated in an oxygen chamber to induce retinopathy. One eye of animals in the OIR group received BMMNC suspension (treated eyes), and the contralateral eye received the same volume of saline injection. Then, all animals underwent funduscopy, angiography, electroretinography, histopathology and immunohistochemical assessments. Compared to the saline injection group, eyes treated with BMMNC had less vascular tortuosity while veins and arteries had relatively the same caliber, as revealed by fundus examinations. Eyes in the treatment group showed significantly elevated photopic and scotopic B waves amplitude. Neovascularization in the inner retinal layer and apoptosis of neural retina cells in the treatment group was significantly lower compared to untreated eyes. Also, BMMNC transplantation decreased glial cell activation and VEGF expression in ischemic retina. Our results indicate that intravitreal injection of BMMNC reduces neural and vascular damages and results in recovered retinal function in rat model of ROP. Ease of extraction without in vitro processing, besides the therapeutic effects of BMMNCs, make this source of cells as a new choice of therapy for ROP or other retinal ischemic diseases.


Sensitivity enhancement of graphene/zinc oxide nanocomposite-based electrochemical impedance genosensor for single stranded RNA detection.
An efficient electrochemical impedance genosensing platform has been constructed based on graphene/zinc oxide nanocomposite produced via a facile and green approach. Highly pristine graphene was synthesised from graphite through liquid phase sonication and then mixed with zinc acetate hexahydrate for the synthesis of graphene/zinc oxide nanocomposite by solvothermal growth. The as-synthesised graphene/zinc oxide nanocomposite was characterised with scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy and X-ray diffractometry (XRD) to evaluate its morphology, crystallinity, composition and purity. An amino-modified single stranded DNA oligonucleotide probe synthesised based on complementary Coconut Cadang-Cadang Viroid (CCCVd) RNA sequence, was covalently bonded onto the surface of graphene/zinc oxide nanocomposite by the bio-linker 1-pyrenebutyric acid N-hydroxysuccinimide ester. The hybridisation events were monitored by electrochemical impedance spectroscopy (EIS). Under optimised sensing conditions, the single stranded CCCVd RNA oligonucleotide target could be quantified in a wide range of 1.0×10-11M to 1.0×10-6 with good linearity (R =0.9927), high sensitivity with low detection limit of 4.3×10-12M. Differential pulse voltammetry (DPV) was also performed for the estimation of nucleic acid density on the graphene/zinc oxide nanocomposite-modified sensing platform. The current work demonstrates an important advancement towards the development of a sensitive detection assay for various diseases involving RNA agents such as CCCVd in the future.


Background modelling of diffraction data in the presence of ice rings.
An algorithm for modelling the background for each Bragg reflection in a series of X-ray diffraction images containing Debye-Scherrer diffraction from ice in the sample is presented. The method involves the use of a global background model which is generated from the complete X-ray diffraction data set. Fitting of this model to the background pixels is then performed for each reflection independently. The algorithm uses a static background model that does not vary over the course of the scan. The greatest improvement can be expected for data where ice rings are present throughout the data set and the local background shape at the size of a spot on the detector does not exhibit large time-dependent variation. However, the algorithm has been applied to data sets whose background showed large pixel variations (variance/mean > 2) and has been shown to improve the results of processing for these data sets. It is shown that the use of a simple flat-background model as in traditional integration programs causes systematic bias in the background determination at ice-ring resolutions, resulting in an overestimation of reflection intensities at the peaks of the ice rings and an underestimation of reflection intensities either side of the ice ring. The new global background-model algorithm presented here corrects for this bias, resulting in a noticeable improvement in R factors following refinement.


Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro.
Vascular endothelial growth factor (VEGF)-mediated angiogenesis mediates tumour growth and metastasis. Meningiomas are primarily benign, slow-growing, highly vascularised tumours. Aside from VEGF, there is little data on the function of major angiogenic proteins in meningiomas. The VEGFA, platelet-derived growth factor B (PDGFB), and their respective receptors - VEGF receptor 2 (KDR) and PDGF receptor β (PDGFRβ) - were quantified using real-time PCR and a TaqMan Protein Assay in meningiomas in vivo and in vitro. The effect of VEGFA and PDGFB on cell proliferation and the tyrosine phosphorylation of PDGFRβ were examined. Most meningiomas displayed no KDR protein expression but elevated PDGFRβ levels. Exogenous VEGFA stimulation significantly increased cell proliferation. The PDGFRβ inhibition before stimulation with VEGFA abolished the proliferative stimuli. The VEGFA induced concentration-dependent PDGFRβ tyrosine phosphorylation comparable to PDGFB-induced PDGFRβ tyrosine phosphorylation. The PDGFRβ inhibitors gambogic acid, sunitinib, and tandutinib equally impaired the migration of meningioma cells. In addition, gambogic acid suppressed the VEGFA-induced PDGFRβ tyrosine phosphorylation. Collectively, our data suggest that VEGFA primarily regulates VEGF-mediated migration through PDGFRβ in meningiomas. The inhibitory effect of gambogic acid and tandutinib against meningioma growth in vitro suggests that selective PDGFRβ inhibitors, in combination with VEGF inhibitors, should be evaluated further as potential therapies for recurrent and malignant meningiomas.


Tutorial dialogues and gist explanations of genetic breast cancer risk.
The intelligent tutoring system (ITS) BRCA Gist is a Web-based tutor developed using the Shareable Knowledge Objects (SKO) platform that uses latent semantic analysis to engage women in natural-language dialogues to teach about breast cancer risk. BRCA Gist appears to be the first ITS designed to assist patients' health decision making. Two studies provide fine-grained analyses of the verbal interactions between BRCA Gist and women responding to five questions pertaining to breast cancer and genetic risk. We examined how "gist explanations" generated by participants during natural-language dialogues related to outcomes. Using reliable rubrics, scripts of the participants' verbal interactions with BRCA Gist were rated for content and for the appropriateness of the tutor's responses. Human researchers' scores for the content covered by the participants were strongly correlated with the coverage scores generated by BRCA Gist, indicating that BRCA Gist accurately assesses the extent to which people respond appropriately. In Study 1, participants' performance during the dialogues was consistently associated with learning outcomes about breast cancer risk. Study 2 was a field study with a more diverse population. Participants with an undergraduate degree or less education who were randomly assigned to BRCA Gist scored higher on tests of knowledge than those assigned to the National Cancer Institute website or than a control group. We replicated findings that the more expected content that participants included in their gist explanations, the better they performed on outcome measures. As fuzzy-trace theory suggests, encouraging people to develop and elaborate upon gist explanations appears to improve learning, comprehension, and decision making.


Surface vs. solution hybridization: effects of salt, temperature, and probe type.
Hybridization thermodynamics on solid supports are compared with those in solution for two types of hybridization probe, DNA and uncharged morpholino oligonucleotides of identical sequences. Trends in hybridization affinity are discussed with respect to ionic strength, temperature, and surface behavior.


Cloning and expression of a Trichinella spiralis putative glutathione S-transferase and its elicited protective immunity against challenge infections.
Glutathione-S-transferase (GST) is a widespread multigene family of detoxification enzymes. The vaccination of mice with recombinant GST of 24 kDa from Trichinella spiralis elicited a low immune protection against challenge infection. The objective of this study was to characterize the T. spiralis putative GST gene (TspGST) encoding a 30.8 kDa protein and to evaluate its potential as a candidate antigen for anti-Trichinella vaccine. The full-length cDNA sequence of TspGST from T. spiralis muscle larvae (ML) was expressed in E. coli. The enzymatic activity and antigenicity of the rTspGST were identified by spectrophotometry, Western blot, and ELISA. The expression of TspGST at T. spiralis various stages was investigated by RT-PCR and indirect immunofluorescent test (IIFT). Serum level of total IgG, IgG1, and IgG2a antibodies against rTspGST were measured by ELISA. The immune protection produced by vaccination with rTspGST against T. spiralis was evaluated. The sequencing results showed that the cDNA of TspGST was 840 bp, and encoded a protein of 279 amino acids, which had a molecular size of 30.8 kDa and a pI of 5.21. Its amino acid sequence shares 37% similarity with TsGST. The rTspGST protein had enzymatic activity of GST. On Western blot and ELISA analysis, the native TspGST protein with 30.8 kDa in crude antigens derived from adult worms (AW), newborn larvae (NBL), infective intestinal larvae (IIL) and ML was recognized by anti-rTspGST sera, but the ML ES antigens could be not recognized by anti-rTspGST sera. Expression of TspGST was found in all of T. spiralis various stages (AW, NBL, ML, and IIL). An immunolocalization analysis identified TspGST in different stages (mainly in cuticles) of the nematode. The mice vaccinated with the rTspGST elicited Th2-predominant immune responses, showed a 34.38% reduction of adult worms and a 43.70% reduction of muscle larvae. Immunization with rTspGST produced a partial immune protection, and the rTspGST could be regarded as a potential candidate target for an anti-Trichinella vaccine.


Influence of imaging on the negative appendectomy rate in pregnancy.
Appendectomy is the most common non-gynecologic surgery performed during pregnancy. Little data exist on the accuracy of imaging studies in the diagnosis of appendicitis in pregnancy. The objective of this study was to evaluate the probability of ultrasound and computed tomography (CT) scan in diagnosing appendicitis in pregnancy, as reflected in the negative appendectomy rate. We retrospectively reviewed the charts of 86 pregnant women who underwent an appendectomy between January 1, 1997 and January 1, 2006. Patients were divided into three groups: clinical evaluation, ultrasound, and ultrasound followed by a CT scan. The clinical evaluation group had 13 patients, with a negative appendectomy rate of 54% (7/13). Fifty-five patients underwent an ultrasound alone, with a negative appendectomy rate 36% (20/55). In the ultrasound/CT group (n=13), the negative appendectomy rate was 8% (1/13). There was a significant reduction in the negative appendectomy rate in the ultrasound/CT scan group compared to clinical evaluation group (54 vs 8%, p<0.05). This reduction was not achieved in the ultrasound group when compared to the clinical evaluation group or the ultrasound/CT group (p=0.05). A significant reduction was achieved when the ultrasound/CT group was compared to the patients in the ultrasound only group who had a normal or inconclusive ultrasound (p<0.05). Our data documents a very high negative appendectomy rate in the pregnant patient. We recommend an ultrasound followed by a CT scan in patients with a normal or inconclusive ultrasound.


Human adenosine deaminase and chromosome 20.
In patients exhibiting in marrow cells deletion of the long arm of chromosome 20, the specific activities of adenosine deaminase in cells of the peripheral blood are normal. This suggests that the gene for adenosine deaminase is not localized to the distal segment of the long arm of this chromosome.


Peptidoglycan precursor synthesis along the sidewall of pole-growing mycobacteria.
Rod-shaped mycobacteria expand from their poles, yet d-amino acid probes label cell wall peptidoglycan in this genus at both the poles and sidewall. We sought to clarify the metabolic fates of these probes. Monopeptide incorporation was decreased by antibiotics that block peptidoglycan synthesis or l,d-transpeptidation and in an l,d-transpeptidase mutant. Dipeptides complemented defects in d-alanine synthesis or ligation and were present in lipid-linked peptidoglycan precursors. Characterizing probe uptake pathways allowed us to localize peptidoglycan metabolism with precision: monopeptide-marked l,d-transpeptidase remodeling and dipeptide-marked synthesis were coincident with mycomembrane metabolism at the poles, septum and sidewall. Fluorescent pencillin-marked d,d-transpeptidation around the cell perimeter further suggested that the mycobacterial sidewall is a site of cell wall assembly. While polar peptidoglycan synthesis was associated with cell elongation, sidewall synthesis responded to cell wall damage. Peptidoglycan editing along the sidewall may support cell wall robustness in pole-growing mycobacteria.


One-pot synthesis of 5-hydroxymethylfurfural directly from starch over SO(4)(2-)/ZrO2-Al2O3 solid catalyst.
The synthesis of 5-hydroxymethylfurfural (HMF) directly from starch was studied in dimethyl sulfoxide-water. The effects of catalyst variation, reaction time, water content, catalyst loading and temperature on the reaction were investigated. The SO(4)(2-)/ZrO(2)-Al(2)O(3) catalyst was found to act as a bifunctional catalyst with high activity for both hydrolysis and dehydration of starch. HMF yield of 55% was obtained after 6h at 423K for the reaction of starch (the molar ratio of water to glucose in starch is 44/1) over the SO(4)(2-)/ZrO(2)-Al(2)O(3) catalyst, which bears high acidity and moderate basicity with Zr/Al molar ratio of 1:1.


Perioperative factors associated with aneurysm sac size changes after endovascular aneurysm repair.
To identify the perioperative factors associated with aneurysm size changes after endovascular aortic aneurysm repair (EVAR). Between August, 2008 and December, 2014, 187 patients underwent EVAR treatment in our institution. The subjects of this study were 135 of these patients without peripheral artery disease, who were followed up with computed tomography (CT) for 3 years. Significant aneurysm size change was defined as sac size change of more than 5 mm from the baseline. Sac enlargement was identified in 25 patients (18.5%) and sac shrinkage was identified in 59 (43.7%) patients. The factors associated with sac enlargement were postoperative pulse wave velocity (OR: odds ratio 3.80, p = 0.047), prevalence of a type 2 endoleak 1 week after surgery (OR 4.26, p = 0.022), inner diameter (OR 1.10, p = 0.005), and distance from the lower renal artery to the terminal aorta (OR 1.05, p = 0.017). The factors associated with sac shrinkage were prevalence of a type 2 endoleak (OR 0.09, p < 0.001) and preoperative pulse wave velocity (OR 0.32, p = 0.022). The factors independently associated with type 2 endoleak were the use of an Excluder device (OR 3.99, p = 0.002) and the length of the aneurysm (OR 1.02, p = 0.027). Inner diameter, treatment length, perioperative pulse wave velocity, and type 2 endoleak were associated with sac size changes after EVAR.


A Novel Universal Detection Agent for Time-Gated Luminescence Bioimaging.
Luminescent lanthanide chelates have been used to label antibodies in time-gated luminescence (TGL) bioimaging. However, it is a challenging task to label directly an antibody with lanthanide-binding ligands and achieve control of the target ligand/protein ratios whilst ensuring that affinity and avidity of the antibody remain uncompromised. We report the development of a new indirect detection reagent to label antibodies with detectable luminescence that circumvents this problem by labelling available lysine residues in the linker portion of the recombinant fusion protein Linker-Protein G (LPG). Succinimide-activated lanthanide chelating ligands were attached to lysine residues in LPG and Protein G (without Linker) and the resulting Luminescence-Activating (LA-) conjugates were compared for total incorporation and conjugation efficiency. A higher and more efficient incorporation of ligands at three different molar ratios was observed for LPG and this effect was attributed to the presence of eight readily available lysine residues in the linker region of LPG. These Luminescence-Activating (LA-) complexes were subsequently shown to impart luminescence (upon formation of europium(III) complexes) to cell-specific antibodies within seconds and without the need for any complicated bioconjugation procedures. The potential of this technology was demonstrated by direct labelling of Giardia cysts and Cryptosporidium oocysts in TGL bioimaging.


Adrenal depletion during hypoglycemia without participation of the Golgi apparatus.
Adrenal depletion in rats due to hypoglycemia was effected by prolonged administration of adrenaline, without artificial increase in insulin levels. In spite of significantly enhanced catecholamine turnover in this stadium Golgi complexes - which are usually reported to develop hypertrophy during adrenal depletion using insulin induced hypoglycaemia - could never be observed. This leads to the conclusions, that firstly the presence of hypertrophic Golgi complexes is not necessarily linked with increased catecholamine turnover and secondly that permanent adrenalin application suppresses and insulin application promotes the formation of Golgi systems. Moreover, our electromicrographs do strongly suggest, that catecholamine turnover is linked with the rough endoplasmatic reticulum.


Adolescent female with withdrawal psychosis following abrupt termination of ziprasidone.
It is widely known that discontinuation reactions can occur after neuroleptics are stopped resulting in dyskinesia through its effect on the nigrostriatal pathway. Less discussed is the concept of "supersensitivity psychosis" which has been described as a rapid onset of psychosis after a neuroleptic medication has been withdrawn. Although the concept of supersensitivity psychosis has been described with the discontinuation of some neuroleptics, it has not been described with ziprasidone. Furthermore, the following case report is the first time that this phenomenon has been described in an adolescent patient who has discontinued ziprasidone. Reasons for supersensitivity psychosis are explored in addition to suggestions about precautions about prescribing neuroleptics in young people.


Profile of free and conjugated quercetin content in different Italian wines.
Quercetin and its structural derivatives are natural compounds belonging to the flavonoid class, widely distributed in plants. Beneficial physiological activities have been attributed to them, but some require deeper investigation. In this paper the content of quercetin and five analogues (quercetin-3-glucoside, quercetin-3-rutinoside, quercetin-3-ramnoside, quercetin-3-arabinoglucoside, 4'-O-methylquercetin) were determined by HPLC-ESI-MS/MS in wines made of different varieties of red and white vines. The aim was a comparative study focusing on quercetin and on the contribution of related compounds in twenty wines coming from different part of Italy. Wines produced from Sangiovese and Nero d'Avola, monovarietal grapes, were richest in quercetin compounds and our results were compared to our previous study and to other investigations. The proposed method resulted simple, fast, economical, and suitable for the analysis of quercetin analogues without the need of hydrolysis and falls in the optic of a 360° characterization of active wine compounds, with nutraceutical properties.


Salvage of the mandibular staple bone plate following bone infection.
Two cases of previously unreported complications associated with implantation of a mandibular staple bone plate are presented. One was a proven case of chronic osteomyelitis, and the other had a close clinical and radiographic resemblance to osteomyelitis. It is suspected in both cases that complications were due to the use of a dull twist drill that caused local tissue injury. Differences in the clinical courses are believed to be related to the degree of oral hygiene after surgery, with a more severe infection occurring in the patient who maintained extremely poor home care. There is the possibility that some degree of osteoporosis was present in the same patient that may also have influenced the clinical course. While the salvage of implants in areas of osteomyelitis is controversial, it was shown to be justifiable in these cases. Crucial to such salvage is the selection of an antibiotic that is effective against the organisms involved and safe for prolonged use. Cefotaxime and clindamycin were used in the cases reported and proved to be effective and without adverse effect. Although it will take time to see to what degree bone refills the affected areas, it appears at present that the resorptive process has ceased and that bone regeneration is in progress. Prevention of the complications reported here is believed to be possible with the use of sharp drills, slow drilling speed, copious cool irrigation, appropriate antibiotic prophylaxis, and meticulous oral hygiene.


Efficient purification of His-tagged protein by superparamagnetic Fe3O4/Au-ANTA-Co2+ nanoparticles.
Superparamagnetic Fe3O4/Au nanoparticles were synthesized and surface modified with mercaptopropionic acid (MPA), followed by conjugating Nα,Nα-Bis(carboxymethyl)-l-lysine hydrate (ANTA) and subsequently chelating Co(2+). The resulting Fe3O4/Au-ANTA-Co(2+) nanoparticles have an average size of 210 nm in aqueous solution, and a magnetization of 36 emu/g, endowing the magnetic nanoparticles with excellent magnetic responsivity and dispersity. The Co(2+) ions in the magnetic nanoparticle shell provide docking site for histidine, and the Fe3O4/Au-ANTA-Co(2+) nanoparticles exhibit excellent performance in binding of a His-tagged protein with a binding capacity of 74 μg/mg. The magnetic nanoparticles show highly selective purification of the His-tagged protein from Escherichia coli lysate. Therefore, the obtained Fe3O4/Au-ANTA-Co(2+) nanoparticles exhibited excellent performance in the direct separation of His-tagged protein from cell lysate.


Glare disability devices for cataractous eyes: a consumer's guide.
We evaluated five commercially available glare testers to determine how accurately each device predicted outdoor Snellen acuity in cataract patients. Predicted outdoor Snellen acuity was compared to actual Snellen outdoor acuity for the Miller-Nadler glare tester, the brightness acuity tester (BAT), the InnoMed true vision analyzer (TVA), the VisTech VCT 8000, and the EyeCon 5. All five devices were evaluated in a single series of eyes. We ranked the five glare testers as follows based upon their ability to predict outdoor Snellen acuity within one Snellen line: (1) BAT (73%), (2) TVA (69%), (3) VisTech VCT 8000 (56%), (4) Miller-Nadler (47%), and (5) EyeCon 5 (15%). All five devices were also evaluated for their capacity to provide false negative or false positive results and for testing time per eye, test difficulty level for the patient, versatility, upgrading capacity, examining room adaptability, and price. We concluded that glare testing of cataract patients is necessary to measure visual disability and that glare testing devices vary in their ability to predict outdoor vision.


Further studies on the environmental capabilities of fungi: interactions of salinity, ultraviolet irradiation, and temperature in Penicillium.
A strain of Penicillium currently under study in this laboratory has revealed some unexpected features in response to salts and UV-radiation. These responses include: (a) stimulation of growth by one molar NaCl and KCl at 23 degrees but not at 5 degrees C, (b) total inhibition by LiCl and RbCl at 5 degrees but not at 23 degrees C, (c) stimulation by 254 nm radiation (2 x 10(6) erg cm-2 min-1, 30-90 minutes) at 23 degrees and 5 degrees C, and (d) very elevated growth rates at 23 degrees after incubation at 5 degrees C.


Low-frequency motion in membranes. The effect of cholesterol and proteins.
Nuclear magnetic resonance (NMR) relaxation techniques have been used to study the effect of lipid-protein interactions on the dynamics of membrane lipids. Proton enhanced (PE) 13C-NMR measurements are reported for the methylene chain resonances in red blood cell membranes and their lipid extracts. For comparison similar measurements have been made of phospholipid dispersions containing cholesterol and the polypeptide gramicidin A+. It is found that the spin-lattice relaxation time in the rotating reference frame (T1 rho) is far more sensitive to protein, gramicidin A+ or cholesterol content than is the laboratory frame relaxation time (T1). Based on this data it is concluded that the addition of the second component to a lipid bilayer produces a low-frequency motion in the region of 10(5) to 10(7) Hz within the membrane lipid. The T1 rho for the superimposed resonance peaks derived from all parts of the phospholipid chain are all influenced in the same manner suggesting that the low frequency motion involves collective movements of large segments of the hydrocarbon chain. Because of the molecular co-operativity implied in this type of motion and the greater sensitivity of T1 rho to the effects of lipid-protein interactions generally, it is proposed that these low-frequency perturbations are felt at a greater distance from the protein than those at higher frequencies which dominate T1.


Long-Term Cardiovascular Risk in Women With Hypertension During Pregnancy.
History of a hypertensive disorder of pregnancy (HDP) among women may be useful to refine atherosclerotic cardiovascular disease risk assessments. However, future risk of diverse cardiovascular conditions in asymptomatic middle-aged women with prior HDP remains unknown. The purpose of this study was to examine the long-term incidence of diverse cardiovascular conditions among middle-aged women with and without prior HDP. Women in the prospective, observational UK Biobank age 40 to 69 years who reported ≥1 live birth were included. Noninvasive arterial stiffness measurement was performed in a subset of women. Cox models were fitted to associate HDP with incident cardiovascular diseases. Causal mediation analyses estimated the contribution of conventional risk factors to observed associations. Of 220,024 women included, 2,808 (1.3%) had prior HDP. The mean age at baseline was 57.4 ± 7.8 years, and women were followed for median 7 years (interquartile range: 6.3 to 7.7 years). Women with HDP had elevated arterial stiffness indexes and greater prevalence of chronic hypertension compared with women without HDP. Overall, 7.0 versus 5.3 age-adjusted incident cardiovascular conditions occurred per 1,000 women-years for women with versus without prior HDP, respectively (p = 0.001). In analysis of time-to-first incident cardiovascular diagnosis, prior HDP was associated with a hazard ratio (HR) of 1.3 (95% CI: 1.04 to 1.60; p = 0.02). HDP was associated with greater incidence of CAD (HR: 1.8; 95% CI: 1.3 to 2.6; p < 0.001), heart failure (HR: 1.7; 95% CI: 1.04 to 2.60; p = 0.03), aortic stenosis (HR: 2.9; 95% CI: 1.5 to 5.4; p < 0.001), and mitral regurgitation (HR: 5.0; 95% CI: 1.5 to 17.1; p = 0.01). In causal mediation analyses, chronic hypertension explained 64% of HDP's association with CAD and 49% of HDP's association with heart failure. Hypertensive disorders of pregnancy are associated with accelerated cardiovascular aging and more diverse cardiovascular conditions than previously appreciated, including valvular heart disease. Cardiovascular risk after HDP is largely but incompletely mediated by development of chronic hypertension.


A survey of expectations and understanding of palliative radiotherapy from patients with advanced cancer.
To assess patients' understanding of their illness and expectations of palliative radiotherapy for symptomatic metastases before and after consultation and to explore the relationship between response and demographics/Edmonton Symptom Assessment Scale (ESAS) scores. In total, 100 participants completed a survey before and after consultation from March to October 2009. Descriptive statistics and statistical analyses were conducted to compare responses and to determine any relationship between responses and demographics or ESAS variables. Up to 25% believed their cancer was curable; there was no change in belief that radiotherapy would cure their cancer (17% before and 15% after) or prolong their life (40% before and 45% after). There were significant differences in radiotherapy expectation for symptom relief (P=0.0094) and for patients who did not know the role of radiotherapy (P=0.0025). Patient anxiety was reduced after consultation on questions about radiotherapy (P<0.001), concerns on effectiveness (P<0.0001) and side-effects of treatment (P<0.0001); 96, 24 and 46% said after consultation that they were satisfied with information from the team, better understood their diagnosis of cancer and the role of radiotherapy, respectively. A significant proportion of patients with advanced disease believe their cancer is curable, expect that radiotherapy will cure their cancer and prolong their life despite understanding the intent of radiotherapy is for symptom relief. After consultation, patients say they have a better understanding of their cancer and feel more confident about treatment. More work is needed to improve patients' understanding of their illness and expectations of the role of palliative radiotherapy.


[The analysis of polycyclics in vegetable samples].
PAH analyses in vegetables are often difficult to carry out; therefore two different clean-up methods, which allow elimination of interfering matrix components such as essential oils, waxes, carotinoids and chlorophylls were developed. Clean-up of 32 different vegetables samples consisted of either Bio-Beads S-X3 chromatography or semi-preparative HPLC on silica gel Si-60. PAH were determined by capillary GC-MS, which allowed the application of deuterium-labeled internal standards. The results are presented; higher PAH contamination was detected in kale and parsley.


HLA alleles associated with asparaginase hypersensitivity in Chinese children.
Asparaginase is an important drug to treat childhood haematological malignancies. Data on the association between human leukocyte antigens (HLA) and asparaginase hypersensitivity among Chinese are lacking. We conducted a retrospective study to identify HLA alleles associated with asparaginase hypersensitivity among Chinese children with acute lymphoblastic leukaemia (ALL), mixed phenotype leukaemia and non-Hodgkin lymphoma (NHL), who received asparaginases with HLA typing performed between 2009 and 2019. 107 Chinese patients were analysed. 66.3% (71/107) developed hypersensitivity to at least one of the asparaginases. HLA-B*46:01 (OR 3.8, 95% CI 1.4-10.1, p < 0.01) and DRB1*09:01 (OR 4.3, 95% CI 1.6-11.4, p < 0.01) were significantly associated with L-asparaginase hypersensitivities, which remained significant after adjustment for age, gender and B cell ALL [HLA-B*46:01 (adjusted OR 3.5, 95% 1.3-10.5, p = 0.02) and DRB1*09:01 (OR 4.4, 95% CI 1.6-13.3, p < 0.01)].


DNA-mediated genetic transformation of mouse embryos and bone marrow--a review.
In recent years, new gene transfer systems have been developed which allow molecularly cloned genetic material to be introduced into whole organisms. These systems include the microinjection of DNA into mammalian embryos, transfection of DNA into mouse bone marrow cells, and the infection of early embryos with retroviruses. Exogenous DNA appears to integrate randomly into the host genome. The production of transgenic mice by injection of DNA into mouse embryos has rapidly gained importance as an experimental tool for the study of gene regulation during development. Through this technique, recombinant molecules of any type can be introduced into one-celled embryos, and thus can be used to study development from its earliest stages. DNA sequences have been shown to integrate and transmit through the germ line to subsequent generations as mendelian traits. Transgenic mice carrying various gene constructs have been successfully exploited for the elucidation of factors which determine tissue specificity of gene expression as well as the level of gene control. Phenotypic changes related to expression of foreign genes have also been observed. This experimental approach thus promises to rapidly solve many of the heretofore most challenging problems in developmental genetics. Insertion of foreign genes has also made possible the creation of insertional mutants which manifest themselves most frequently as recessives. Such mutations can be readily studied at the molecular level by using the transferred material as a probe for recovery of the affected host sequence from genomic libraries. Many of these same problems have been addressed by introducing retroviral DNA into mouse embryos. Here, the sequences used for transfer have been limited to retroviral genes, but nonetheless these experiments have been profitably exploited for studies both of gene regulation and mutagenesis. Gene transfer systems are being developed allowing the experimenter to transfer DNA into bone marrow cells of mice, after which the recipient cells can be reintroduced into lethally irradiated histocompatible animals. This system has the advantage that selection can be applied during the gene transfer process such that the expression of the foreign material is assured. In addition, these experiments have created a model system for production of animals carrying a subpopulation of cells which is highly resistant to a toxic agent. This system has the potential for therapeutic application to man.


Paternal Smoking Before Conception and During Pregnancy Is Associated With an Increased Risk of Childhood Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis of 17 Case-Control Studies.
Current evidence regarding the association between paternal smoking before conception or during pregnancy and the risk of childhood acute lymphoblastic leukemia (ALL) are inconsistent. We aimed to systematically summarize the current evidence regarding this potential association. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE), we systematically retrieved PubMed, Embase, Web of Science, and Scopus, screened relevant literature, and assessed the methodologic quality of the included studies. We calculated the pooled estimates using random-effects models. We assessed statistical heterogeneity by I values and χ tests for the Cochrane Q statistic. We further investigate the dose-response relation using 2-stage nonlinear models. A total of 17 case-control studies were identified, and the synthesized risk ratios (RRs) for smoking before conception (RR=1.15, 95% confidence interval: 1.04-1.27) and during pregnancy (RR=1.20, 95% confidence interval: 1.12-1.28) were both statistically significant. Moreover, the dose-response analysis showed a positive association as well. Current evidence from observational studies suggests the association between paternal smoking before conception or during pregnancy and the increased risk of childhood ALL, which needs to be confirmed in prospective studies.