A preliminary study of the phycological degradation of natural stone masonry.
For many years it has been realised that the weathering of stone is not merely determined by physical and chemical factors but also by biological agents. When the stone in question is a historic building or monument, the damage done constitutes an irretrievable loss of our heritage and history. Laboratory studies have commenced in Paisley to study the effect of photoautotrophs on the major sedimentary rock forming minerals, with a view to expanding this work to study the overall effect of these micro-organisms on heritage masonry. Tests were carried out on Albite, Calcite, Dolomite, Orthoclase, Siderite and Quartz, using axenic cultures of the following: Chlorella vulgaris, Chlorococcum tetrasporum, Scenedesmus obliquus, Oocystis marsonii, Stichococcus bacillaris. The rock chips were immersed in either water or bolds basal media and exposed to a mix of the micro-organisms listed above and then tested weekly for their pH, fortnightly for the waters chemical composition using inductively coupled plasma-atomic emission spectrometry (ICP-AES) and visually utilising the university's SEM facilities. Work so far has revealed biologically mediated etching of minerals, a well-defined pH profile over a period of 90 days, as well as a variety of elemental release patterns for the different minerals.


Surgical Management of Adrenocortical Carcinoma: An Evidence-Based Approach.
Adrenocortical carcinoma frequently presents with sequelae of steroid precursor overproduction and has a proclivity for aggressive local growth, early metastasis, and recurrence. En bloc surgical resection with negative margins is the cornerstone of therapy for localized disease, and re-resection has a role in selected recurrent cases. Presence of occult micrometastatic disease at the time of presentation is confirmed by frequent distant failure after apparent negative margin resection. Data for many aspects of therapy are limited or nonexistent. This review critically considers existing evidence with a particular focus on surgical management.


[Prevalence and factors associated with abdominal obesity and excess weight among adults from Maranhão, Brazil].
To determine the prevalence of excess body weight and abdominal obesity and assess the association with socioeconomic, demographic and behavioral factors among adults of Maranhão, Brazil. Multistage cluster sample investigated through a household survey on 1,005 adults aged 20 to 59 years (393 men and 612 women). Anthropometric measures: weight, height and waist circumference (WC) were assessed. Abdominal obesity was defined as WC > 80 for women and WC > 94 for men. Body mass index (BMI), weight in kilograms divided by the square of height in meters, > 25 kg/m² was considered excess body weight. The dependent variable was divided into four categories: normal BMI and WC, excess body weight only (EBW), abdominal obesity only (AO) and abdominal obesity with excess body weight (AOEBW). Multinomial logistic regression was used for statistical analysis and estimates took the complex sampling design into account. Among men the prevalence of AO was 1.3%, EBW 20.3% and AOEBW 27.5%. Among women 15.5% presented AO, 1.3% EBW and 42.0% AOEBW. There was a significant statistical difference among sexes (p value < 0.001). In the multivariable analysis, among men, schooling > 9 years and living with a partner were factors associated with higher prevalence of EBW. Age > 35 years, family income > two minimum wages and living with a partner were associated with higher prevalence of AOEBW. Among women, age > 35 and living with a partner were factors associated with AO. Age > 35 years, living with a partner and schooling < 9 years were associated with a higher prevalence of AOEBW. the prevalence of EBW was higher among men whereas AO prevailed among women. Factors associated with excess body weight, abdominal obesity and both excess body weight and abdominal obesity varied.


Transition Metal Complexes with Flufenamic Acid for Pharmaceutical Applications-A Novel Three-Centered Coordination Polymer of Mn(II) Flufenamate.
Five complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) with non-steroidal anti-inflammatory drug, flufenamic acid were synthesized: (1) [Mn3(fluf)6EtOH)(H2O)]·3EtOH; (2) [Co(fluf)2(EtOH)(H2O)]·H2O; (3) [Ni(fluf)2(EtOH)(H2O)]·H2O; (4) [Cu(fluf)2·H2O]; (5) [Zn(fluf)2·H2O]. All complexes were characterized by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The crystal structure of 1 was determined by the single crystal X-ray diffraction technique. It crystallizes in the triclinic space group P with three independent Mn(II) cations, six coordinated flufenamato ligands augmented with water and ethanol molecules in the inner coordination sphere. In this crystal, manganese atoms are multiplied by symmetry and form infinite, polymeric chains which extend along the [001] dimension. The Hirshfeld Surface analysis revealed changes in interaction assemblies around all metal centers. The antioxidant and antimicrobial activities were established for all complexes and free ligand for comparison. All compounds exhibit good or moderate bioactivity against Gram-positive bacteria and yeasts.


Total cutaneous harvesting from an amputated foot--two free flaps used for acute reconstruction.
Loss of weight-bearing skin of the foot produces a difficult reconstructive problem. A case is presented of severe bilateral lower limb trauma in which the right leg was amputated below the knee and two free flaps taken from the amputated foot were used for cover of the damaged left foot and the amputation stump.


Cycloreversion of azetidines via oxidative electron transfer. steady-state and time-resolved studies.
Cycloreversion of cis- and trans-1,2,3-triphenylazetidine (c-2 and t-2) is achieved by electron transfer to (tris(4-bromophenyl)aminium radical cation (5 (*+)). Stepwise C-N and C-C bond cleavage of azetidine radical cations leads to cis- and trans-stilbene, together with N-benzylideneaniline, as final products. Mechanistic evidence is provided by quenching studies, using laser flash photolysis to generate 5 (*+) from its neutral precursor.


Effects of topically applied antiandrogenic compounds on sebaceous glands of hamster ears and flank organs.
Growth of sebaceous glands in the ears and flank organs of castrated male hamsters is dependent on androgen substitution. Taking this for granted, a study was done to compare the effects of topical antiandrogenic treatment in vivo on the morphology and size of sebaceous glands with the concomitant changes in in vitro metabolism of 3H-testosterone. The role of dihydrotestosterone in sebaceous gland stimulation was thereby investigated. Topical treatment was carried out with the androgen antagonist 17 alpha-propylmesterolone (PM), with 4-androsten-3-one-17 beta-carboxylic acid (17 beta-C), and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), both described as specific 4-steroid-5 alpha-reductase inhibitors, and with progesterone (PRO), which is an androgen receptor antagonist with 5 alpha-reductase inhibiting properties. Regrowth of sebaceous glands after castration and substitution with testosterone propionate or dihydrotestosterone could be inhibited by topical PM and PRO. This occurred irrespective of the influence on testosterone metabolism and irrespective of the mode of substitution. 4-MA, on the other hand, while exhibiting strong 5 alpha-reductase inhibition in vitro, was ineffective in reducing sebaceous gland sizes in vivo. The compound 17 beta-C was ineffective in every respect. In no case were systemic antiandrogenic effects on prostates and seminal vesicles observed. Our results support the view that the DHT formation rate has no regulatory function for growth of sebaceous glands in hamsters and that PM and PRO counteract the androgenic stimulus by their competitive antagonistic binding to the androgen receptor, but not by their influence on testosterone metabolism.


A potential influence of rhizobium activity on the availability of nitrogen to legume herbivores.
Evidence is presented which supports the hypothesis that allantoin, a ureide that is a major storage form of nitrogen (N) in legumes whose N is derived from N-fixation, is not utilizable by at least some insect herbivores. We suggest that the nutritive quality of soybean foliage for Mexican bean beetles is influenced by soil nitrogen level through its impact on rhizobial activity which indirectly alters the proportion of ureide-nitrogen to amino acid-nitrogen without affecting total Kjeldahl-nitrogen. This may provide a basic mechanism for protecting the nitrogen stores of legumes from herbivory while avoiding the metabolic burden of secondary compound production.


Cathodic trypsin-like immunoreactivity in serum: influence of sex, age, renal function, food and diurnal variation.
Radioimmunologically determined cathodic trypsin-like immunoreactivity (TLI) in serum was positively correlated with age (Spearman's rho = 0.40, p less than 0.001) and negatively correlated with estimated creatinine clearance (Spearman's rho = -0.31, p less than 0.01) in healthy adults (37 women, 27 men) under standard conditions. Women had higher TLI concentrations than men (median value 358 micrograms trypsin standard/l compared with 283 micrograms trypsin standard/l, p less than 0.02). A clinically significant uptake of cathodic trypsin from the intestine to the blood is not likely because no change was found in serum concentrations of TLI and the two major protease inhibitors (alpha 1-antitrypsin and alpha 2-macroglobulin) one hour after a standard meal. No diurnal variation of TLI in serum was found in a group of 12 healthy subjects. The results indicate that due consideration must be given to sex, age and renal function of the persons used in reference groups for TLI determination.


[3H]MK-801 binding to well-washed rat brain membranes following cessation of chronic phencyclidine treatment.
Rats were implanted with osmotic minipumps SC that infused either saline or 10 mg/kg/day phencyclidine (PCP) for 10 days, a regimen that produces dependence to PCP. At the end of this 10-day infusion period, the pumps were removed and the rats were sacrificed either immediately or at various time points (12 h, 1, 2, and 7 days) after pump removal. The saturation binding parameters of [3H]MK-801 were then determined in well-washed cortical/hippocampal membranes prepared from these rats. Neither the Bmax nor the Kd of [3H]MK-801 binding in membranes of PCP-treated rats differed from that determined using membranes from saline-treated rats at any time point studied. These results suggest that alterations in PCP receptors do not play a major role in the production of PCP dependence.


Assessment of kidney function in children by enzymatic determination of 2- or 24-h creatinine clearance: comparison with inulin clearance.
Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients.


The Hemodynamic Effects of Aortic Regurgitation in Patients Supported by a HeartMate 3 Left Ventricular Assist Device.
Aortic regurgitation (AR) is a common complication following left ventricular assist device (LVAD) implantation. We evaluated the hemodynamic implications of AR in patients with HeartMate 3 (HM3) LVAD at baseline and in response to speed changes. Clinically stable outpatients supported by HM3 who underwent a routine hemodynamic ramp test were retrospectively enrolled in this analysis. Patients were stratified based on the presence of at least mild AR at baseline speed. Hemodynamic and echocardiographic parameters were compared between the AR and non-AR groups. Sixty-two patients were identified. At the baseline LVAD speed, 29 patients (47%) had AR, while 33 patients (53%) did not. Patients with AR were older and supported on HM3 for a longer duration. At baseline speed, all hemodynamic parameters were similar between the groups including central venous pressure, pulmonary capillary wedge pressure, pulmonary arterial pressures, cardiac output and index, and pulmonary artery pulsatility index (p > 0.05 for all). During the subacute assessment, AR worsened in some, but not all, patients, with increases in LVAD speed. There were no significant differences in 1-year mortality or hospitalization rates between the groups, however, at 1-year, ≥ moderate AR and right ventricular failure (RVF) were detected in higher rates among the AR group compared to the non-AR group (45% vs. 0%; p < 0.01, and 75% vs. 36.8%; p = 0.02, respectively). In a cohort of stable outpatients supported with HM3 who underwent a routine hemodynamic ramp test, the presence of mild or greater AR did not impact the ability of HM3 LVADs to effectively unload the left ventricle during early subacute assessment. Although the presence of AR did not affect mortality and hospitalization rates, it resulted in higher rates of late hemodynamic-related events in the form of progressive AR and RVF.


Arginine kinetics are altered in a pilot sample of adolescents and young adults with Barth syndrome.
Barth syndrome (BTHS) is a rare, X-linked cardiomyopathy that is characterized by abnormalities in glucose and lipid metabolism, with less known regarding amino acid metabolism. This pilot study characterized whole-body arginine kinetics and found lower arginine rate of appearance into plasma (0.69 ± 0.09 vs. 0.88 ± 0.06 μmol/kgFFM/min, p < 0.01) and arginine non-oxidative disposal rate (0.64 ± 0.11 vs. 0.80 ± 0.03 μmol/kgFFM/min, p < 0.02) in adolescents and young adults with BTHS compared to Controls. This study provides a foundation for more in-depth studies on how arginine and potentially other amino acid abnormalities contribute to the pathology and clinical manifestations of BTHS.


miR-146a-5p Modulates Adult Hippocampal Neurogenesis Deficits Through Klf4/p-Stat3 Signaling in APP/PS1 Mice.
Alzheimer's disease (AD) is the most common neurodegenerative disease, and currently, no effective treatment strategies exist for this condition. MicroRNAs (miRNAs) have emerged as promising therapeutic targets of AD. Previous studies have highlighted the significant role of miR-146a-5p in regulating adult hippocampal neurogenesis (AHN). Here, we aimed to investigate whether miR-146a-5p plays a role in the mechanisms of AD. We employed quantitative real-time PCR (qRT-PCR) to assess the expression of miR-146a-5p. Additionally, we examined the expression of Krüppel-like factor 4 (Klf4), Signal transducer and activator of transcription 3 (Stat3), and phosphorylated Stat3 (p-Stat3) using western blot analysis. Furthermore, we validated the interaction between miR-146a-5p and Klf4 using a dual-luciferase reporter assay. Immunofluorescence staining was employed to evaluate AHN. And Contextual fear conditioning discrimination learning (CFC-DL) experiment was used to detect pattern separation. Our findings in the hippocampus of APP/PS1 mice revealed upregulated levels of miR-146a-5p and p-Stat3, while Klf4 levels were downregulated. Interestingly, both miR-146a-5p antagomir and p-Stat3 inhibitor obviously rescued neurogenesis and pattern separation in APP/PS1 mice. Moreover, application of miR-146a-5p agomir reversed the protective effects of Klf4 upregulation. These findings open new avenues for protection against AD through the modulation of neurogenesis and cognitive decline via the miR-146a-5p/Klf4/p-Stat3 pathway.


Ambulatory mental health liaison research: a review and preview.
Mental health liaison in primary care is a complex technology requiring scientific study and validation if we are to know when, where, and how to utilize it. Earlier studies have raised as many questions as they have resolved. Recommendations for future research are presented in relation to such issues as: How should mental health consultation/liaison be defined? How should consultation/liaison studies be prioritized? What aspects of consultation/liaison should be studied? What methodologies are appropriate?


Activation mechanisms of endothelial NF-kappaB, IKK, and MAP kinase by tert-butyl hydroperoxide.
Lipid peroxidation plays a major role in vascular dysfunction and age-related cardiovascular diseases. A major product of lipid peroxidation, tert-butyl hydroperoxide (t-BHP), has been reported to modulate vascular reactivity and cellular signaling. To better understand vascular abnormality, we set out to delineate the activation mechanism of nuclear factor kappa B (NF-kappaB) by t-BHP and the regulation of MAPK in endothelial cells. The results showed that t-BHP induces NF-kappaB activation by an inhibitor of kappaB (IkappaB) phosphorylation through IkappaB kinase (IKK) activation. Our data from this t-BHP study also showed increased p38 MAP kinase and ERK activity; however, interestingly, t-BHP showed no influence on JNK. Pretreatment with the p38 MAP kinase inhibitor, SB203580 and the ERK1/2 inhibitor, PD98059, prevented t-BHP-induced increases in p65 translocation, NF-kappaB luciferase activity, and phospho-IKKalpha/beta. Data suggested that t-BHP induces NF-kappaB activation through the IKK pathway, which involves p38 MAPK and ERK activation. This study illustrates a role of t-BHP in NF-kappaB activation and MAPK related-signaling pathways. The t-BHP-induced activation of NF-kappaB and MAPK could be a major player in vascular dysfunctions, as seen in oxidative stressed responses and the vascular inflammatory process.


[Functional results of an operation for forming an "artificial stomach" after gastrectomy and subtotal distal resection of the stomach].
The operations of plastic substitution of the resected stomach with a transplant of the jejunum were fulfilled in 81 patients. The aim of the operations was to establish the natural passage through the duodenum. Of 55 able-bodied patients 31 returned to their regular work, 14 patients changed their work to easier. An investigation of the main parameters of metabolism and of the questionnaires distributed among the patients have shown a high level of the "quality of life" of the patients operated upon at later terms after operations. The involvement of the duodenum in digestion due to the jejunal plasty of the resected stomach made the disorders of digestion rarer, improved the quality of life of the patients at later terms after operation, thus promoting their social and labor rehabilitation.


[2+4] Cycloaddition Product of an Amidinate Substituted Dialumene with Toluene.
Reduction of LAlI2 (L=PhC(Ni Pr2 C6 H3 )2 ) with two equivalents of KC8 in toluene affords the [2+4]cycloaddition product of a dialumene with toluene. The mechanism for the formation of product complex was investigated using density functional theory (DFT) methods.


Training proprioception with sound: effects of real-time auditory feedback on intermodal learning.
Our study analyzed the effects of real-time auditory feedback on intermodal learning during a bilateral knee repositioning task. Thirty healthy participants were randomly allocated to control and experimental groups. Participants performed an active knee joint repositioning task for the four target angles (20°, 40°, 60°, and 80°) bilaterally, with or without additional real-time auditory feedback. Here, the frequency of auditory feedback was mapped to the knee's angle range (0-90°). Retention measurements were performed on the same four angles, without auditory feedback, after 15 min and 24 hours. A generalized knee proprioception test was performed after the 24-h retention measurement on three untrained knee angles (15°, 35°, and 55°). Statistical analysis revealed a significant enhancement of knee proprioception, shown as a lower knee repositioning error with auditory feedback. This enhancement of proprioception also persisted in tests performed between the 5th and 6th auditory-motor training blocks (without auditory feedback). Enhancement in proprioception also remained stable during retention measurements (after 15 min and 24 h). Similarly, enhancement in the generalized proprioception on untrained knee angles was evident in the experimental group. This study extends our previous findings and demonstrates the beneficial effects of real-time auditory feedback to facilitate intermodal learning by enhancing knee proprioception in a persisting and generalized manner.


Visualization of the glomerular endothelial glycocalyx by electron microscopy using cationic colloidal thorium dioxide.
Biological material itself appears with poor contrast in electron microscopy (EM), due to its composition mostly of light elements. Classical staining agents such as osmium tetroxide, uranyl acetate, and lead citrate preserve and/or stain cellular structures such as membranes, cytoplasm, and organelles well for EM. However, extracellular polymeric substances (EPS) show no or only poor contrast with these staining agents. The endothelial glycocalyx in blood vessels consists mainly of proteoglycans. It can be visualized by EM only by additional staining with heavy metal ions such as copper (Alcian blue, cupromeronic blue), ruthenium (ruthenium red), or lanthanum. Best results are achieved by combined perfusion of fixative and stain. Cationic hydrous thorium dioxide colloids (named here cThO2) trace acidic groups in EPS. We describe here the use of cThO2 to visualize the glomerular endothelial glycocalyx in the mouse kidney. cThO2 shows high electron density and binds to a continuous layer of up to a few hundred nanometers thickness on the glomerular endothelium, as well as on epithelia in other blood vessels in perfused animals. The observed staining pattern gives rise to periodic densities, with a spacing varying between 50 and 200 nm, depending on the overall layer thickness, which varies between below 50 up to 300 nm. Due to high electron density of the used cThO2 particles, the introduced method allows distinct imaging and precise fine structural analysis of the endothelial glycocalyx.


Time-resolved molecular transport across living cell membranes.
It is shown that the nonlinear optical phenomenon known as second-harmonic generation can be used for label-free, time-resolved study of the transport of molecules through living cell membranes. The adsorption and transport of a 300-Da molecular-mass hydrophobic ion at the Escherichia coli membrane is observed. Remarkably, at low ion concentrations, the second-harmonic generation technique clearly exposes a multistep molecular transport process: Transport of the molecular ion across the outer and cytoplasmic membranes of the Gram-negative bacteria is recorded, in sequence, in time. Fitting of the data to a multiprocess kinematic model reveals that the transport of this hydrophobic ion through the outer membrane is much faster than through the cytoplasmic membrane, likely reflecting the effectiveness of ion transport porins. The observations illustrate an experimental means for studying the interactions of small molecules with cell membranes.


Odontoplasty associated with clinical crown lengthening in management of extensive crown destruction.
The aim of this study was to evaluate the clinical outcome of teeth submitted to odontoplasty during clinical crown lengthening surgery (CCLS), when compared to their contralateral non-operated teeth. Fourteen patients submitted to odontoplasty during CCLS were evaluated according to plaque index, bleeding on probing, probing depth and final restoration outcome (total success, relative success and failure). The mean follow-up period was 13.57 (± 8.00) months, and ranged from 6 to 24 months. Twelve cases presented total success of the final rehabilitation and 2 cases presented relative success. The cases of relative success were due to the necessity for a new periodontal intervention (scalling). No differences were observed with respect to periodontal parameters (P>0.05) and the patients that showed relative success presented generalized poor oral hygiene. The odontoplasty during clinical crown lengthening surgery is a feasible procedure in the management of extensive crown destruction.


Performance Measurement Part I: Foundational Knowledge for Measure Development.
As medicine is moving towards performance and outcome-based payment, and is transitioning away from productivity-based systems, value is now being appraised in healthcare through "performance measures." Over the past few decades, assessment of clinical performance in healthcare has been essential in ensuring safe and cost-effective patient care. The Centers for Medicare & Medicaid Services (CMS) is further driving this change with measurable, outcomes-based national payer incentive payment systems. With the continually evolving requirements in healthcare reform focused on value-based care, there is a growing concern that clinicians, particularly dermatologists, may not understand the scientific rationale of healthcare quality measurement. As such, in order to help dermatologists understand the healthcare measurement science landscape to empower them to engage in the performance measure development and implementation process, the first article in this 2-part continuing medical education series reviews the value equation, historic and evolving policy issues, and the American Academy of Dermatology's (AAD) approach to performance measurement development to provide the required foundational knowledge for performance measure developers.


Effect of hydrostatic pressure on spectra of heme compounds.
Increase in hydrostatic pressure shifts the absorption bands of oxy-, carboxy-, and deoxyhemoglobin and myoglobin toward the red by 0.4 to 0.7 nm corresponding to a change in extinction coefficient of from 4 to 8% at the peak of the difference spectrum. The pressure difference spectrum for oxyhemoglobin closely resembles the difference spectrum described by Adams and Schuster ((1974) Biochem. Biophys. Res. Commun. 58, 528-533) following addition of inositol hexaphosphate to oxyhemoglobin. A similar shift was observed for derivatives of dimethyl-deuterohemedisulfonate in both Fe2+ and Fe3+ forms indicating that the protein is not required for this effect, in contrast to earlier reports of T. L. Fabry and J. W. Hunt ((1968) Arch. Biochem. Biophys. R3, 428-429) and Q.H. Gibson and F.G. Carey ((1975) Biochem. Biophys. Res. Commun. 67, 747-571) who were unable to observe changes in aqueous solutions of protoheme derivatives.


A method for increasing permeability in O2/N2 separation with mixed-matrix membranes made of water-stable MIL-101 and polysulfone.
Water-stable MIL-101 microcrystals adhere well to polysulfone (PSF) and yield a very robust mixed-matrix MIL-101-PSF membrane for the O(2)/N(2) separation with a selectivity of 5-6 and an unsurpassed O(2) permeability increase by a factor of four to above 6 barrer for MIL-101 loadings of 24%.


Aluminium and lead abnormalities in children on haemodialysis: relationship with some medications.
The determination of toxic elements in the biological samples of human beings is an important clinical procedure. This study was performed to investigate the prevalence of abnormal blood contents of 2 trace elements (TEs), aluminum (Al),and lead (Pb) in hemodialysis (HD) patients and to analyze their relationship with the medications, such as CaCO(3), Ca acetate, 1,25-dihydroxy vit. D(3), and erythropoietin (EPO), as well as hematocrit level. We included 43 patients on maintenance HD and they had continued the previously mentioned medications for at least 3 months. None of the patients were on Al containing phosphate binding agents. Serum aluminum and lead levels were significantly increased than in the healthy controls, but levels of both of them were far below toxic values. Male patients had higher mean levels of lead than did females. A strong positive correlation was found between serum Al and serum Pb levels among patients (r = 0.075, p = 0.0001).The serum level of Pb was positively correlated with the serum albumin in HD patients (r = 0.45, p = 0.03). Both serum aluminium and lead levels positively correlated with the EPO dose taken by the patients (r = 0.77, p = 0.0001 and r = 0.67, p = 0.0001 respectively). The blood level of trace metals of these HD patients was not related to their medications except for the EPO dose. However, caution must be exercised in interpreting this result as dose and duration of medication may play an important role. Al and Pb over load may be considered from the causes of inadequate response to epoetin therapy.


A transcriptomic analysis of serial-cultured, tonsil-derived mesenchymal stem cells reveals decreased integrin α3 protein as a potential biomarker of senescent cells.
Mesenchymal stem cells (MSCs) have been widely used for stem cell therapy, and serial passage of stem cells is often required to obtain sufficient cell numbers for practical applications in regenerative medicine. A long-term serial cell expansion can potentially induce replicative senescence, which leads to a progressive decline in stem cell function and stemness, losing multipotent characteristics. To improve the therapeutic efficiency of stem cell therapy, it would be important to identify specific biomarkers for senescent cells. Tonsil-derived mesenchymal stem cells (TMSCs) with 20-25 passages were designated as culture-aged TMSCs, and their mesodermal differentiation potentials as well as markers of senescence and stemness were compared with the control TMSCs passaged up to 8 times at the most (designated as young). A whole-genome analysis was used to identify novel regulatory factors that distinguish between the culture-aged and control TMSCs. The identified markers of replicative senescence were validated using Western blot analyses. The culture-aged TMSCs showed longer doubling time compared to control TMSCs and had higher expression of senescence-associated (SA)-β-gal staining but lower expression of the stemness protein markers, including Nanog, Oct4, and Sox2 with decreased adipogenic, osteogenic, and chondrogenic differentiation potentials. Microarray analyses identified a total of 18,614 differentially expressed genes between the culture-aged and control TMSCs. The differentially expressed genes were classified into the Gene Ontology categories of cellular component (CC), functional component (FC), and biological process (BP) using KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis. This analysis revealed that those genes associated with CC and BP showed the most significant difference between the culture-aged and control TMSCs. The genes related to extracellular matrix-receptor interactions were also shown to be significantly different (p < 0.001). We also found that culture-aged TMSCs had decreased expressions of integrin α3 (ITGA3) and phosphorylated AKT protein (p-AKT-Ser473) compared to the control TMSCs. Our data suggest that activation of ECM-receptor signaling, specifically involved with integrin family-mediated activation of the intracellular cell survival-signaling molecule AKT, can regulate stem cell senescence in TMSCs. Among these identified factors, ITGA3 was found to be a representative biomarker of the senescent TMSCs. Exclusion of the TMSCs with the senescent TMSC markers in this study could potentially increase the therapeutic efficacy of TMSCs in clinical applications.


Medial and anterior-posterior ligament stability of the human knee, measured with a stress apparatus.
The five ligaments studied act with a symphonic harmony to provide stability to the knee. The SMCL was of major importance in medial knee stability. The other ligament which provided the most dramatic contribution to knee stability was the PC. It was the only ligament which when sectioned resulted in a significant posterior anterior drawer instability and on three occasions produced a jerk test.


Agonist-induced cytosolic calcium oscillations originate from a specific locus in single hepatocytes.
Digital imaging fluorescence microscopy of fura-2-loaded hepatocytes in primary culture has been used to examine the changes of cytosolic free Ca2+ ([Ca2+]i) in response to receptor activation by alpha 1-adrenergic agonists and vasopressin at the subcellular level. Agonist-induced Ca2+ oscillations did not occur synchronously within the cell but originated from a specific region adjacent to the cell membrane and then propagated throughout the rest of the cell, with each oscillation within a series originating from the same locus. Furthermore, hormones acting through different receptors produced Ca2+ waves with similar rates of progress (20-25 microns.s-1) which originated from the same subcellular locus. For a given cell, the rate of progress and amplitude of the Ca2+ waves were independent of applied agonist concentration and were unaffected by depletion of extracellular Ca2+. The kinetics of Ca2+ increase at different points within the cell indicated that the Ca2+ waves were not driven by diffusion but were characteristic of a self-propagating mechanism. Significantly, when cells were treated with A1F-4 to directly activate the G-protein which couples receptor occupancy to [Ca2+]i mobilization, the origin and kinetics of the Ca2+ waves were identical to those observed with hormonal stimulation. It is proposed that the spatial organization of the intracellular Ca2+ release mechanisms may have significance in the regulation of the asymmetric metabolic functions of hepatocytes and other functionally polarized cells.


Impact of a restriction in the number of embryos transferred on the multiple pregnancy rate.
To study the impact of the introduction of reimbursement of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) laboratory costs in Belgium which is linked to an embryo transfer strategy leading to prevention of multiple pregnancies. The impact on the incidence of multiple and twin pregnancy rate as well as on ongoing pregnancy rate in our centre is calculated. Observational cohort study of all patients in the first year (July 1, 2003-June 30, 2004) since the implementation of the law and comparison of ongoing pregnancy rate and multiple pregnancy rate of our centre with Belgian data. Our results of one year of IVF/ICSI since reimbursement of laboratory costs show a total conception rate of 42.2% with 29.7% ongoing pregnancies beyond 25 weeks amenorrhea. The multiple pregnancy rate was 8.5% including five monozygotic twin pregnancies. These data show an important decline of multiple pregnancy rate when compared to Belgian data (2002) with 24.4% multiple pregnancy rate in the year prior to reimbursement. The introduction of reimbursement of IVF/ICSI laboratory costs coupled to a restriction in the number of embryos for transfer has reached the goal of halving the multiple pregnancy rate since its introduction while maintaining an optimal ongoing pregnancy rate.


Thermochemistry of aqueous solutions of alkylated nucleic acid bases. VI. Enthalpies of hydration of 2-alkyl-9-methyladenines.
Enthalpies of solution in water, delta H0sol, and vant'Hoff enthalpies of sublimation, delta H0subl, were determined experimentally for a number of crystalline 2-alkyl derivatives of 9-methyladenine: m2(2,9)Ade, e2m9Ade, pr2m9Ade and but2m9Ade. Standard enthalpies of hydration, delta H0hydr derived from these data were corrected for the calculated cavity terms, delta H0cav, to yield enthalpies of interaction, delta H0int, of the solutes with their hydration shells. The apparent residual contribution of alkyl groups, R, to the enthalpy of interaction delta delta H0int (R) was found to increase linearly with the number of CH2 groups added upon alkyl substitution, whereas this contribution calculated per unit area of the water-accessible molecular surface, SB, of alkyl residues delta delta H0int (R): delta SB(R) appeared constant over the whole series of the compounds investigated. This indicates that alkyl groups substituted at the C(2) carbon atom of the adenine contribute additively to the van der Waals' part of the enthalpy of interaction and do not affect the electrostatic part of the energy of interaction of the solutes with their hydration shells.


[A histologic observation of bone formation induced by subperiosteal implantation of resorbable porous block beta-tricalcium phosphate on calvarial surface in rabbits].
By the histologic observation of samples, understanding the osteoconductive histologic behaviour and resorbable mechanism of beta-tricalcium phosphate (beta-TCP). Porous block beta-TCP samples were implanted into calvarial surface. Tissue slices dyed with methods of HE and Masson's were observed by microscope and compared with hydroxyapatite(HA). Beta-TCP had the osteoconductivity,as well as HA, plentiful new bone penetrated into materials from the calvarial surface. There was no new bone under the periost obviously. A large number of rhagiorine cells swallowing beta-TCP had been observed. Beta-TCP has osteoconductivity, can be used as a substitution for atrophic alveolar ridge augmentation. The function of rhagiorine cell swallowing beta-TCP is the essential resorbable mechanism of beta-TCP.


Photocatalytic overall water splitting under visible light by TaON and WO3 with an IO3-/I- shuttle redox mediator.
Photocatalytic water splitting into H2 and O2 under visible-light irradiation (lambda > 420 nm) is demonstrated using the oxynitride Pt-TaON for H2 evolution and a Pt-WO3 catalyst for O2 evolution in an IO3-/I- shuttle redox-mediated system.


The conjugated auxin indole-3-acetic acid-aspartic acid promotes plant disease development.
Auxin is a pivotal plant hormone that regulates many aspects of plant growth and development. Auxin signaling is also known to promote plant disease caused by plant pathogens. However, the mechanism by which this hormone confers susceptibility to pathogens is not well understood. Here, we present evidence that fungal and bacterial plant pathogens hijack the host auxin metabolism in Arabidopsis thaliana, leading to the accumulation of a conjugated form of the hormone, indole-3-acetic acid (IAA)-Asp, to promote disease development. We also show that IAA-Asp increases pathogen progression in the plant by regulating the transcription of virulence genes. These data highlight a novel mechanism to promote plant susceptibility to pathogens through auxin conjugation.


Giving wings to logic: Mary Everest Boole's propagation and fulfilment of a legacy.
In his influential Laws of Thought (1854), the mathematician George Boole presented a formulation of logic using algebraic expressions and manipulations. His widow, Mary Everest Boole, undertook an ambitious project of disseminating his ideas by introducing lay audiences to the law of pulsation, a prescription for correct reasoning that incorporates two of his fundamental insights. Contemporary scholarship presents a fragmented picture of Mary Boole, regarding her largely as a source of information on the religio-psychological impetus for her husband's contributions to logic, among other matters. Some studies rightly acknowledge that her better-known commentary on educational reform relates to a promotion of the Laws of Thought, yet these typically fail to expand on how she articulated such relationships for readers. This paper provides a more complete understanding of her efforts by examining texts on various subjects motivated by a dedication to propagating as much as fulfilling the intellectual legacy she associated with her husband. In doing so it considers her interventions - like those undertaken by other Victorian women who sought to cultivate scientific enterprises - within a contextual framework broad enough to include strategic responses to cultural realities and possibilities.


Radioimmunoassay of plasma progesterone, testosterone, total estrogen and immunoreactive gonadotropin in the nesting and non-nesting green sea turtle, Chelonia mydas (L.).
Plasma progesterone, testosterone, total estrogens and immunoreactive gonadotropin were measured in nesting and non-nesting sea turtles, Chelonia mydas. Progesterone and gonadotropin concentrations were significantly higher in nesting than in non-nesting turtles, testosterone was not significantly different in either group and total estrogens appeared to be slightly in the nesting group.


"Such Behaviors Are Not in My Home Village, I Got Them Here": A Qualitative Study of the Influence of Contextual Factors on Alcohol and HIV Risk Behaviors in a Fishing Community on Lake Victoria, Uganda.
In Uganda, elevated HIV prevalence in fishing communities along Lake Victoria have been attributed in part to heavy alcohol use, but qualitative research is needed to understand the contextual factors influencing alcohol and sexual risk. Eight focus group discussions were conducted (n = 50; 23 male, 27 female) in Gerenge, Uganda with five occupational groups: fishermen, fishmongers, alcohol-sellers, commercial sex workers, and restaurant owners. Data was analyzed using content analysis. Alcohol use was prevalent and said to influence risky sex. Sex-related alcohol expectancies and occupational factors influenced individuals to drink during sex and structural factors related to the built environment, economy, and policy were identified as key contributors to both alcohol use and sexual risk in general. The findings highlight alcohol reduction as an important component of HIV/AIDS prevention and suggest structural interventions should be prioritized in this context.


Mesonephric hyperplasia can cause abnormal cervical smears: report of three cases with review of literature.
Hyperplastic mesonephric remnants are an incidental finding in occasional uterine or cervical surgical specimens. We describe three cases in which such remnants were postulated to be the source of abnormal glandular cells in cervical smears. In all three cases abnormal glandular cells were seen in cervical smears. Subsequent histology showed the presence of hyperplastic mesonephric remnants that communicated with the endocervical canal and were likely to be the source of the abnormal glandular cells. We believe that the key features of these cells, which may aid their distinction from other causes of glandular abnormalities, are their loose clustering, lack of significant anisocytosis and cuboidal outlines. We aim to document mesonephric hyperplasia as a possible source for abnormal glandular cells in cervical smears.


Patterns of ICU admissions and outcomes in patients with solid malignancies over the revolution of cancer treatment.
Major therapeutic advances including immunotherapy and targeted therapies have been changing the face of oncology and resulted in improved prognosis as well as in new toxic complications. The aim of this study is to appraise the trends in intensive care unit (ICU) admissions and outcomes of critically ill patients with solid malignancies. We performed a retrospective single-centre study over a 12-year period (2007-2018) including adult patients with solid malignancies requiring unplanned ICU admission. Admission patterns were classified as: (i) specific if directly related to the underlying cancer; (ii) non-specific; (iii) drug-related or procedural adverse events. 1525 patients were analysed. Lung and gastro-intestinal tract accounted for the two main tumour sites. The proportion of patients with metastatic diseases increased from 48.6% in 2007-2008 to 60.2% in 2017-2018 (p = 0.004). Critical conditions were increasingly related to drug- or procedure-related adverse events, from 8.8% of ICU admissions in 2007-2008 to 16% in 2017-2018 (p = 0.01). The crude severity of critical illness at ICU admission did not change over time. The ICU survival rate was 77.4%, without any significant changes over the study period. Among the 1279 patients with complete follow-up, the 1-year survival rate was 33.2%. Independent determinants of ICU mortality were metastatic disease, cancer in progression under treatment, admission for specific complications and the extent of organ failures (invasive and non-invasive ventilation, inotropes/vasopressors, renal replacement therapy and SOFA score). One-year mortality in ICU-survivors was independently associated with lung cancer, metastatic disease, cancer in progression under treatment, admission for specific complications and decision to forgo life-sustaining therapies. Advances in the management and the prognosis of solid malignancies substantially modified the ICU admission patterns of cancer patients. Despite underlying advanced and often metastatic malignancies, encouraging short-term and long-term outcomes should help changing the dismal perception of critically ill cancer patients.


Time use of stroke patients in three rehabilitation hospitals.
The active role of the patient in the rehabilitation hospital requires the efficient use of patient time. Previous work has found that such patients spend a relatively small portion of their day in treatment. In this study 63 stroke patients in three hospitals were observed for two work days each. Fifty observations were made during each day of the patient's location, activity and whom the patient was with. Treatment occupied an average of 31% of the day. Passive behavior took up 42% of patients' time. Discriminant analysis showed that patients in the hospital with a separate stroke unit spent more time in treatment. In spite of quantitative differences, the three hospitals had similar patterns of treatment activity and deployment of staff. Clinical norms for the treatment of stoke across the three hospitals resulted in similar treatment experiences for patients. A system of prospective payment which did not require specific billed treatment hours might allow more flexibility and efficiency in this type of specialty hospital.


Development of a multi-locus typing scheme for an Enterobacteriaceae linear plasmid that mediates inter-species transfer of flagella.
Due to the public health importance of flagellar genes for typing, it is important to understand mechanisms that could alter their expression or presence. Phenotypic novelty in flagellar genes arise predominately through accumulation of mutations but horizontal transfer is known to occur. A linear plasmid termed pBSSB1 previously identified in Salmonella Typhi, was found to encode a flagellar operon that can mediate phase variation, which results in the rare z66 flagella phenotype. The identification and tracking of homologs of pBSSB1 is limited because it falls outside the normal replicon typing schemes for plasmids. Here we report the generation of nine new pBSSB1-family sequences using Illumina and Nanopore sequence data. Homologs of pBSSB1 were identified in 154 genomes representing 25 distinct serotypes from 67,758 Salmonella public genomes. Pangenome analysis of pBSSB1-family contigs was performed using roary and we identified three core genes amenable to a minimal pMLST scheme. Population structure analysis based on the newly developed pMLST scheme identified three major lineages representing 35 sequence types, and the distribution of these sequence types was found to span multiple serovars across the globe. This in silico pMLST scheme has shown utility in tracking and subtyping pBSSB1-family plasmids and it has been incorporated into the plasmid MLST database under the name "pBSSB1-family".


Plasma and vitreous homocysteine concentrations in patients with proliferative diabetic retinopathy.
An increase in plasma concentrations of homocysteine (Hcy) in proliferative diabetic retinopathy (PDR) has been described. The aim of this study was to investigate vitreous Hcy levels in patients with PDR. Plasma and vitreous samples were obtained simultaneously at the time of vitreoretinal surgery from 20 patients with PDR and 12 nondiabetic patients with nonproliferative ocular diseases. Hcy levels were determined by high-performance liquid chromatography. The mean vitreous and plasma Hcy concentrations for the diabetic group were 3.64 +/- 0.65 micromol/L and 16.04 +/- 2.75 micromol/L, respectively. The mean intravitreal and plasma Hcy concentrations for the control group were 1.08 +/- 0.45 micromol/L and 9.18 +/- 3.91 micromol/L, respectively. Both plasma and vitreous Hcy concentrations for the diabetic group were significantly higher than those for the control group (P < 0.001). A statistically significant correlation between vitreous and plasma Hcy concentrations was present only for the diabetic group (r = 0.525; P = 0.017). Vitreous Hcy concentrations were elevated in patients with PDR probably due to breakdown of the blood-retina barrier.


Transformation of glucocorticoid-receptor complexes is accompanied by dissociation of oligomers in intact cells.
The association of glucocorticoid-receptor complexes with other components in vivo has been evaluated by chemical crosslinking of hormone-treated cells. When cells were incubated with hormone at 2 degrees C, before being subjected to crosslinking, most glucocorticoid-receptor complexes were found untransformed, as judged by DEAE-cellulose chromatography, and sedimented as 11-6 S oligomers in sucrose gradients containing 0.3 M NaCl. If crosslinking was performed after cells were treated with hormone at 37 degrees C, about 60% of cytosolic glucocorticoid-receptor complexes were found transformed, and sedimented as 4 S monomers.


Inherited eye disease: cause and late effect.
Molecular genetics has provided relatively few insights into late-onset eye disorders, but epidemiological data indicate that genetic factors are important in some late-onset eye disorders that cause major health burdens. Much clinical genetic research is based on the belief that developmental and late-onset disorders are not necessarily the result of defects in different genes, but are often caused by different mutations in the same collection of genes. Thus, mutations that either abolish or radically change gene function might cause early-onset disorders, whereas more-subtle changes in gene expression might underlie late-onset diseases. We present arguments and examples that indicate that this principle might be a fruitful guide to investigating the causes of late-onset eye disorders.


Anticoagulant activity of synthetic hirudin peptides.
Synthetic peptides based on the COOH-terminal 21 residues of hirudin were prepared in order to 1) evaluate the role of this segment in hirudin action toward thrombin, 2) define the shortest peptide derivative with anticoagulant activity, and 3) investigate the role of tyrosine sulfation in the peptides' inhibitory activities. A hirudin derivative of 20 amino acids, Hir45-64 (derived from residues 45-64 of the hirudin polypeptide), was found to effect a dose-dependent increase in the activated partial thromboplastin time (APTT) of normal human plasma but to have no measurable inhibitory activity toward thrombin cleavage of a tripeptidyl p-nitroanilide substrate. Anticoagulant activity in hirudin derivatives was comparable in peptides of 20, 16, and 12 residues truncated from the NH2 terminus. Additional truncated peptides prepared by synthesis and carboxypeptidase treatment reveal that the minimal sequence of a hirudin peptide fragment with maximal anticoagulant activity is contained within the sequence: NH2-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-COOH. The 12-residue derivative thus identified was reacted with dicyclohexylcarbodiimide in the presence of sulfuric acid to yield a Tyr-sulfated peptide, S-Hir53-64. By comparison to unsulfated peptide, S-Hir53-64 was found to contain a specific inhibitory activity enhanced by one order of magnitude toward increase in APTT and to effect a dose-dependent increase in thrombin time of normal human plasma to yield a 4-fold increase in thrombin time with 2.5 micrograms/ml peptide using 0.8 units/ml alpha-thrombin. Comparison of S-Hir53-64 to hirudin in thrombin time and APTT assays reveals a 50-fold difference in molar specific activities toward inhibition of thrombin. Comparison of antithrombin activities of S-Hir53-64 using a variety of animal thrombins demonstrates greatest inhibitory activity toward murine, rat, and human enzymes and a 10-fold reduced activity toward bovine thrombin.


Gastrin/CCK-like immunoreactivity in endocrine cells and nerves in the gastrointestinal tract of the cod, Gadus morhua, and the effect of peptides of the gastrin/CCK family on cod gastrointestinal smooth muscle.
Immunohistochemistry shows the presence of one or several gastrin/cholecystokinin (CCK)-like peptides in the gastrointestinal tract of the Atlantic cod, Gadus morhua. Immunoreactive (IR) endocrine cells are present mainly in the lower part of the cardiac and in the pyloric stomach, with a concentration to the inner curvature, and in the proximal part of the intestine, especially in the area of the pyloric caeca, after which the population density of IR cells decreases anally. IR nerve fibers are found in the myenteric plexus and muscle layers of the stomach only. Radioimmunoassays, performed with two C-terminal specific gastrin/CCK antisera, confirm the immunohistochemical findings. The highest levels of IR material are found in the mucosa of the pyloric caeca, the proximal intestine, and the pyloric part of the stomach. The smooth muscle layers contain IR material in a decreasing gradient toward the rectum. The excitatory effect of gastrin/CCK-related peptides on gut smooth muscle is investigated in isolated strip preparations of the gut wall. Of the peptides tested, cerulein is the most potent, followed by CCK 8 and gastrin 17, while gastrin 5 is the least effective. Sulphated CCK 8 gives a higher amplitude of the response but in the same concentration range as nonsulphated CCK 8. It is concluded that one or several gastrin/CCK-like peptides are present in the gut of the cod and may be involved in the nervous and endocrine control of the cod gut motility.


Regional and whole-body dual-energy X-ray absorptiometry to guide treatment and monitor disease progression in neuromuscular disease.
Dual-energy x-ray absorptiometry (DEXA) is a safe, noninvasive, inexpensive tool for managing patients with neuromuscular diseases. Regional and whole-body DEXA can be used to guide clinical treatments, such as determining body composition to guide nutritional recommendations, as well as to monitor disease progression by assessing regional and whole-body lean tissue mass. DEXA can also be used as an outcome measure for clinical trials.


New neo-lignan from Acanthopanax senticosus with protein tyrosine phosphatase 1B inhibitory activity.
New neo-lignan, (7S, 8R)-3-hydroxyl-4-methoxyl-balanophonin (1), together with seven known compounds (2-8) were isolated from the EtOAc-soluble extract of Acanthopanax senticosus. The structure of the new neo-lignan was elucidated with spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against PTP1B, VHR and PP1. Among them, the new compound (1) was found to exhibit selective inhibitory activity on PTP1B with IC50 value 15.2 ± 1.4 µM.


Author Correction: Bidirectional regulatory potentials of short-chain fatty acids and their G-protein-coupled receptors in autoimmune neuroinflammation.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Optimal implementation of the 2019 ESC/EAS dyslipidaemia guidelines in patients with and without atherosclerotic cardiovascular disease across Europe: a simulation based on the DA VINCI study.
The impact of the stepwise implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) treatment algorithm on low-density lipoprotein cholesterol (LDL-C) goal attainment was simulated in patients from the DA VINCI study. Monte Carlo simulation was used to evaluate treatment optimisation scenarios, based on a patient's risk category: statin intensification (step 1), addition of ezetimibe (step 2), and addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (step 3). Residual cardiovascular risk and predicted relative and absolute risk reduction (RRR and ARR) in cardiovascular events were assessed. In DA VINCI, 2482 patients did not achieve their 2019 ESC/EAS LDL-C goals and were included in the simulation. In patients without atherosclerotic cardiovascular disease (ASCVD) (n = 962), 27.0% (n = 259) and 57.0% (n = 548) are likely to achieve their LDL-C goals at step 1 and step 2, respectively. Of those at very high risk without ASCVD (n = 74), 88.1% (n = 65) are likely to achieve their LDL-C goals at step 3. In patients with ASCVD (n = 1520), 12.0% (n = 183), 42.1% (n = 641) and 93.2% (n = 1416) are likely to achieve their LDL-C goals at steps 1, 2 and 3, respectively. In patients with and without ASCVD, treatment optimisation may result in mean simulated RRR of 24.0% and 17.7%, respectively, and ARR of 8.1% and 2.6%, respectively. Most patients at high cardiovascular risk are unlikely to achieve LDL-C goals through statin optimisation and ezetimibe, and will require a PCSK9 inhibitor, leading to greater reduction in cardiovascular risk. Amgen.


The case for change: aviation worker wellbeing during the COVID 19 pandemic, and the need for an integrated health and safety culture.
The workplace is an important setting for health protection, health promotion and disease prevention. Currently, health and wellbeing approaches at an aviation organisational level are not addressing both human and safety needs. This issue has been intensified since the COVID 19 pandemic. This paper reports on the findings of a survey pertaining to aviation worker wellbeing and organisational approaches to managing wellbeing and mental health. The survey was administered at two different time periods during the COVID 19 pandemic (2020 and 2021). Collectively, feedback was obtained from over 3000 aviation workers. Survey feedback indicates that aviation workers are experiencing considerable challenges in relation to their health and wellbeing. These challenges are not being adequately addressed at an organisational level, which creates risk both from an individual and flight safety perspective. The descriptive findings of both surveys along with a regression analysis is used to make a principled case for augmenting the existing approach to managing aviation worker wellbeing (including mental health), at both an organisational and regulatory level. It is argued that aviation organisations, with the support of the regulator should implement a preventative, ethical and evidence-based strategy to managing wellbeing and mental health risk. Critically, aviation organisations need to advance and integrated health, wellbeing, and safety culture. This necessitates an alignment of human, business, and safety objectives, as articulated in concepts of corporate social responsibility (CSR) and responsible work. Critically, this approach depends on trust and the specification of appropriate protections, so that aviation workers feel safe to routinely report wellbeing levels and challenges, and their impact on operational safety.


Accelerated Pulsed High-Fluence Corneal Cross-Linking for Progressive Keratoconus.
To report on 2-year results of accelerated corneal collagen cross-linking (CXL) in progressive ectasia using the Avedro KXL system. Prospective interventional case series. A total of 870 patients (1,192 eyes) attending Moorfields Eye Hospital after CXL were included. All patients undergoing CXL had progressive keratoconus. Corneas with a minimum stromal thickness <375 μm were excluded. Riboflavin 0.1% soak duration was 10 minutes. High-fluence pulsed UVA was delivered at 30 mW/cm2 for 4 minutes, with a 1.5-second on/off cycle (total energy 7.2 J/cm2). Subjective refractive, corneal tomography, and specular microscopy were performed at baseline, 6, 12, and 24 months postoperatively. The primary outcome measure was a change in maximum keratometry (Kmax) at 24 months. Twelve- and 24-month follow-up data were available on 543 and 213 patients, respectively (mean age 25.4 ± 6.6 years). In mild cones (Kmax < 55 diopter [D]), mean keratometry remained unchanged at 24 months. In more advanced disease, we observed modest corneal flattening compared to baseline (Kmax 63.2 ± 6.5 D vs 61.9 ± 8.1 D, P = .02), but no significant changes in central keratometry (K1 or K2). Keratometric stabilization was confirmed in 98.3% of eyes. Mean CDVA, manifest refraction and endothelial cell density did not change. Overall, 2.7% of eyes lost more than 2 lines of CDVA. Accelerated pulsed CXL is a safe, effective, and refractively neutral intervention (at 2 years) to halt disease progression in keratoconus.


Study on the effects of alcohol-enhanced air sparging remediation in a benzene-contaminated aquifer: a new insight.
In this study, the effects of medium carbon chain alcohol (1-heptanol)-enhanced air sparging (AS) on the remediation of benzene-contaminated aquifers in different media (medium sand, channelized flow; gravel, bubbly flow) were investigated by comparison with a commonly used surfactant (sodium dodecylbenzene sulfonate (SDBS)). The results showed that the addition of 1-heptanol and SDBS significantly increased the air saturation in AS process under different airflow modes. Combined with water retention curves, 1-heptanol had the same effect on reducing the surface tension of groundwater and stabilizing bubbles as SDBS. In the study of benzene pollution removal, when the removal efficiency of the benzene pollutant exceeded 95%, the time required for surfactant-enhanced AS (SEAS) and alcohol-enhanced AS (AEAS) in medium sand was shortened by 28.6% and 52.4%, respectively, and the time required for SEAS and AEAS in gravel media was shortened by 16.7% and 58.3%, respectively, compared with the time required for AS. This finding indicated that the addition of SDBS or 1-heptanol could significantly increase the removal rate of benzene pollutants. Under the same surface tension conditions, the removal effect of 1-heptanol on the benzene pollutant was better than that of SDBS. This difference was due to the disturbance of the flow field during AEAS process causing the 1-heptanol on the gas-liquid interface to volatilize in the carrying gas, thereby inducing Marangoni convection on the interface, enhancing the gas-liquid mass transfer rate, and increasing the removal rate of benzene on the interface. Therefore, 1-heptanol is promising as a new reagent to enhance AS to remediate groundwater pollution.


Mesocercaria in the skin of man in Louisiana.
Two areas of intradermal swelling removed from the upper thigh and iliac crest of a 43-year-old man in Louisiana were each found to contain a larval trematode about 0.5 mm in length. Based on morphology reconstructed from serial sections, the two worms were identified as a mesocercaria of an undescribed species belonging to the subfamily Alariinae.


3D Muography for the Search of Hidden Cavities.
Muography (or muon radiography) is a technique that exploits the penetration capability of muons, elementary particles similar to electrons but with a mass about 200 times larger. High energy muons are naturally produced in the interactions of cosmic rays with the Earth atmosphere. The measurement of their absorption in matter allows the imaging of the inner structure of large bodies. The technological developments in the detection of elementary particles have opened the way to its application in various fields, such as archaeology, studies of geological structures, civil engineering and security issues. We have developed a new approach to the three-dimensional muography of underground structures, capable of directly localising hidden cavities and of reconstructing their shape in space. Our measurements at Mt. Echia, the site of the earliest settlement of the city of Naples in the 8th century BC, have led us to the discovery of a hidden underground cavity, whose existence was not evident with the usual two-dimensional muography graphs. We demonstrate here that our original approach definitely enhances muography discovery potential, especially in case of complex underground systems.


Mode of action of DL-norgestrel and ethinylestradiol combination in postcoital contraception.
Possible mechanisms of action of a combination of ethinylestradiol (EE) and dl-norgestrel as a postcoital contraceptive agent were studied in 12 healthy female volunteers. An oral dose of 0.1 mg of EE and 1.0 mg of dl-norgestrel was given at the predicted time of ovulation and again 12 hours later. Serum luteinizing hormone, prolactin, progesterone, 17 alpha-hydroxyprogesterone, and estradiol were measured by specific radioimmunoassays in blood samples obtained daily from the 8th day of the menstrual cycle to the 1st day of menses. Hormone profiles suggested that the medication elicited a range of individual variations in pituitary and/or ovarian responses. Histologic examination of the endometrium consistently showed significant alteration in endometrial development with a dissociation in maturation of glandular and stomal components. This postcoital contraceptive acts either by (1) suppressing ovulation or (2) disrupting luteal function by acting directly on the corpus luteum or by interfering with appropriate endometrial responses to ovarian steroids.


Effects of cold adaptation and starvation on sciatic nerve fibers in the frog.
The conditions under which frogs are kept prior to experimentation were found to have a measurable effect on peripheral nerve structure. Frogs kept for 12 weeks at 4 degree C had markedly shrunken sciatic nerve fibers compared with frogs kept at 19 degrees C. Intermediate fiber shrinkage was found for frogs kept at 19 degrees C without feeding. Counts of neurofilaments and microtubules showed that fiber shrinkage was from a preferential loss of filaments, indicating cold- or starvation-induced atrophy of the axon's cyto-skeleton. This effect, however, was superimposed with additional osmotic axonal shrinkage, causing filament densities to increase per area. There were no changes in myelin sheath thickness due to cold adaptation or fasting.


The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: A systematic review and meta-analysis.
Recent epidemiological studies have suggested that there is an association between glycemic control and sleep disturbances in patients with type 2 diabetes, but the extent is unclear. A systematic literature search was performed in nine electronic databases from inception until August 2015 without any language restriction. The search identified 20 studies (eight studies reporting duration of sleep and 15 studies evaluating sleep quality), and 15 were included in the meta-analysis. Short and long sleep durations were associated with an increased hemoglobin A1c (HbA1c) (weighted mean difference (WMD): 0.23% [0.10-0.36], short sleep; WMD: 0.13% [0.02-0.25], long sleep) compared to normal sleep, suggesting a U-shaped dose-response relationship. Similarly, poor sleep quality was associated with an increased HbA1c (WMD: 0.35% [0.12-0.58]). Results of this study suggest that amount of sleep as well as quality of sleep is important in the metabolic function of type 2 diabetes patients. Further studies are needed to identify for the potential causal role between sleep and altered glucose metabolism.


Reconstruction of congenital stenosis of external auditory canal with a postauricular chondrocutaneous flap.
We describe here a new surgical technique for treatment of congenital stenosis of the external auditory canal using a postauricular chondrocutaneous flap. Our technique prevents recurring stenosis by cartilage support and provides a sufficient extension of the canal. The chondrocutaneous flap is safely elevated, easily reaches the canal, and has ample blood supply. It is beneficial for its self-cleaning function that the remnant canal, which contains cerumen glands, is used as part of the reconstructed canal. Six patients with congenital stenosis of the external auditory canal were treated by our procedure. In these patients, three patients were treated by a postauricular approach and the others were treated by an endaural approach. All patients had very satisfactory results.


Development of the Home based Virtual Rehabilitation System (HoVRS) to remotely deliver an intense and customized upper extremity training.
After stroke, sustained hand rehabilitation training is required for continuous improvement and maintenance of distal function. In this paper, we present a system designed and implemented in our lab: the Home based Virtual Rehabilitation System (HoVRS). Fifteen subjects with chronic stroke were recruited to test the feasibility of the system as well as to refine the design and training protocol to prepare for a future efficacy study. HoVRS was placed in subjects' homes, and subjects were asked to use the system at least 15 min every weekday for 3 months (12 weeks) with limited technical support and remote clinical monitoring. All subjects completed the study without any adverse events. Subjects on average spent 13.5 h using the system. Clinical and kinematic data were collected pre and post study in the subject's home. Subjects demonstrated a mean increase of 5.2 (SEM = 0.69) on the Upper Extremity Fugl-Meyer Assessment (UEFMA). They also demonstrated improvements in six measurements of hand kinematics. In addition, a combination of these kinematic measures was able to predict a substantial portion of the variability in the subjects' UEFMA score. Persons with chronic stroke were able to use the system safely and productively with minimal supervision resulting in measurable improvements in upper extremity function.


Immunomodulation by topical particle-mediated administration of cytokine plasmid DNA suppresses herpetic stromal keratitis without impairment of antiviral defense.
We investigated whether the course of herpetic stromal keratitis (HSK) in BALB/c mice could be altered by topical gene-gun-mediated administration of interleukin (IL)-4 or IL-10 plasmid DNA. Corneas of BALB/c mice were transfected with plasmids expressing beta-galactosidase (beta-gal), IL-4, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and pCR3.1 (control) 2 days before Herpes simplex virus-1 (HSV-1; KOS) infection. Development of keratitis and cell infiltration were studied. HSV-1 replication was monitored by plaque assay. Expression of cytokines was detected by enzyme-linked immunosorbent assay. HSV-specific proliferation in the regional lymph nodes and spleens was measured. HSV-1 neutralizing antibody titers and IgG2A/IgG1 ratios were determined. Expression of beta-gal was found in the treated corneas, but not in other tissues. IL-4 or IL-10 plasmid administration induced cytokine production in the corneas. After treatment with 300 psi, the severity of HSK was attenuated (each P<0.05), and the numbers of infiltrating inflammatory cells were lower than in the pCR3.1-treated controls (P<0.001). IL-6, but not IL-1alpha, expression in the cornea was reduced after treatment with IL-4 or IL-10 plasmid DNA. The HSV-1-specific DTH response, corneal Th1 cytokine profile, IgG/IgG2a/IgG1 ratio, neutralizing antibody titers, and virus clearance did not differ between the groups. Thus, topically administered IL-4 and IL-10 plasmid DNA can lead to a milder course of HSK without impeding viral clearance. The gene gun technique for corneal delivery of plasmid cytokine DNA may be useful for modulating local immune responses without affecting antiviral defense.


The radiology corner. Segmental lymphangiectasia of the small bowel.
A case of intestinal lymphangiectasia, limited to a small segment of jejunum, is reported. This finding reflects part of the spectrum of generalized dysplasia of the lymphatic system. A discussion of the pathogenesis, pathophysiology and roentgen features of intestinal lymphangiectasia as part of a systemic disorder is presented.


Le Fort III osteotomy: a new internal positioned distractor.
The treatment of midfacial retrusion, due to congenital midfacial hypoplasia or trauma, is a challenging problem. Conventional Le Fort III osteotomies, with the surgical mobilisation of the entire midface, offers one solution. Distraction osteogenesis has become an accepted, and often preferred, technique for the treatment of severe midfacial hypoplasia. Existing distraction devices have several disadvantages. To overcome some of these disadvantages, an internal and temporal positioned distraction device was developed. The new, internal positioned distractor device was used in 5 patients (age range, 8 to 15 years). Nine distractors were used in 4 patients with midfacial retrusion and 1 patient with hemifacial microsomia. The preoperative planned position of the osteotomized Le Fort III segment was obtained without any complications in all cases. Midface advancement, measured as the anterior displacement of the infraorbital rim, ranged from 14 to 20 mm. The distractor was almost invisible and did not disturb daily activities of the patient. Activation of the distractor was performed by rotation of a small lateral activation rod. These preliminary results encourage the further use of the new distractor device in a larger series of patients.


[Soave operation in congenital and idiopathic megacolon (author's transl)].
70 infants and children (1,5 to 10 years of age) underwent a Soave-operation, 3 deaths. bad 1, satisfying 4, good 62.


The topless plant developmental phenotype explained!
The molecular-genetic cues that regulate plant embryo pattern formation are the subject of intense scrutiny at present. Recent work in Arabidopsis implicates the TOPLESS protein in auxin-dependent transcriptional repression, highlighting once again the crucial role of auxin signaling during embryogenesis.


Beyond LGMD1A: myotilin is a component of central core lesions and nemaline rods.
Myotilin is a Z-disc protein that binds alpha-actinin, gamma-filamin and F-actin. The essential role of myotilin in skeletal muscle is highlighted by the recent observation that autosomal dominant limb girdle muscular dystrophy type 1A is caused by mutations in the human myotilin gene. We studied the expression and subcellular distribution of myotilin in nemaline myopathy, central core disease, centronuclear myopathy, and myopathies with tubular aggregates. A prominent myotilin immunostaining of nemaline rods and core lesions was detected in all ten cases of nemaline myopathy and five cases of central core disease. This renders myotilin a sensitive, though non-specific marker for these structural lesions. Western blot analysis did not indicate an increased myotilin expression in nemaline myopathy muscle. However, the analysis indicated upregulation of a 75 kDa immunoreactive band, very weak in control muscle but previously detected in limb girdle muscular dystrophy 1A samples. Our findings indicate that myotilin is a core structural molecule in nemaline rods and central core lesions and suggest modification of myotilin in nemaline myopathy, and further support the notion that myotilin may have a key role in the dynamic molecular events mediating myofibril assembly in normal and diseased human skeletal muscle.


Functional inactivation of Cdk9 through oligomerization chain reaction.
The oligomerization chain reaction (OCR) strategy is a recently described technique for inactivation of target proteins that function as homoassociate complexes. This novel strategy is based on the fusion of self-associating coiled-coil (CC) domain of the nuclear factor promyelocytic leukemia (PML) to target proteins. Here, we present the successful application of the OCR strategy for inactivation of the heterodimeric Cdk9/cyclin T1 complex. Cyclin T1/Cdk9 (P-TEFb) complex is a positive regulator of gene transcription, whose function is underlined by the ability to phosphorylate the carboxyl-terminal domain (CTD) of the RNA polymerase II conferring productive transcript elongation. Fusion of the CC domain to Cdk9 leads to the formation of high molecular complexes to which the endogenous cyclin T1 is recruited. The CC-Cdk9 chimera effectively inhibits HIV-1 Tat activation, whose transcription activity is exquisitely dependent upon cyclin T1/Cdk9 function. Furthermore, expression of CC-Cdk9 protein inhibits cell proliferation, as shown by colony-formation assay. Collectively, our findings add further support to the OCR strategy for functional inactivation of hetero-associated factors such as the Cdk9/cyclin T1 complex, and highlight a putative function of Cdk9 in cell growth control.


Rapid kinetics of Ca2+-induced fusion of phosphatidylserine/phosphatidylethanolamine vesicles. The effect of bilayer curvature on leakage.
We have employed both small unilamellar vesicles (SUV) and large unilamellar vesicles formed by the reverse phase evaporation technique (REV) to study the initial kinetics of membrane aggregation and fusion. Stopped flow measurements of the calcium-induced changes in the turbidity of SUV and REV, formed from 1:1 (mol/mol) mixtures of bovine phosphatidylserine (PS) and Escherichia coli phosphatidylethanolamine (PE), were used to follow particle aggregation. Simultaneous measurements of the fluorescence resonance energy transfer from N-(7-nitro2,1,3-benzoxadiazol-4-yl) (NBD)-PE to rhodamine (Rho)-PE incorporated into the vesicle bilayers established that 1) both initial aggregation and fusion can be described as a bimolecular process and 2) the rate-limiting step of membrane fusion is aggregation. Thus fusion takes place in the microsecond time domain. Parallel experiments, which simultaneously measured aggregation and the dequenching of encapsulated carboxyfluorescein (CF) in the presence and absence of antifluorescein antibodies in the suspension medium, established that the small unilamellar vesicles rapidly lose their contents of CF as they fuse. On the other hand, the first few cycles of fusion of the large unilamellar vesicles are nonleaky, but leakage develops within 1-2 s as the particles grow in size. Thus the results demonstrate that the SUV are poor models for the study of nonleaky fusion, while the REV must be carefully tested before unambiguous interpretation of fusion assays involving the formation of tight complexes (such as the terbium-dipicolinic assay) can be made. NBD-PE undergoes very rapid, Ca2+-promoted changes in quantum yield which can obscure the resonance energy transfer signals. Thus data from the NBD-PE/Rho-PE energy transfer pair must be carefully scrutinized for artifacts.


Synthesis of 3-Substituted-clavams: Antifungal Properties, DD-Peptidase and beta-Lactamase Inhibition.
The [2+2]cycloaddition of chlorosulfonyl isocyanate to vinyl and (Z)-propenyl ethers derived from the 2-O-sulfonylated (R)- and (S)-1-(furyl-2')-1,2-ethanediols furnished the 4-alkoxy-azetidin-2-ones with a good to moderate stereoselectivity. The intramolecular alkylation of the beta-lactam nitrogen atom led to the corresponding 3-(furyl-2')- and 6-methyl-3-(furyl-2')-clavams. The transformation of the furyl residue into an alkoxycarbonyl group led to clavams related to the natural compounds. The synthesized clavams exhibited moderate inhibitory activities against DD-peptidase 64-575 and beta-lactamase (penase) as well as antifungal activities.


Natural history of arteriosclerotic thoracic aortic aneurysms.
Out of 28 patients with arteriosclerotic aortic aneurysm seen between 1965 and 1975, 22 were not surgically repaired. Of these 22 patients, 9 subsequently died of rupture and 7 of unrelated cardiovascular disease, and 6 are living at the time of this study. Mean survival for the group is less than 3 years. All but 1 rupture occurred in aneurysms larger than 10 cm, and recent increase in size preceded rupture in all patients for whom serial roentgenograms were available. This study documents the high risk of rupture of arteriosclerotic aortic aneurysms of the descending thoracic aorta and suggests a more uniform use of surgical management depending on the patient's age and underlying state of health.


Vesicular cholesterol in bile. Relationship to protein concentration and nucleation time.
A study was done to determine whether the nucleation time was related to the amount of cholesterol carried in vesicles. Bile was obtained from cholesterol gallstone patients and controls. Gel-exclusion chromatography was used to separate vesicles and micelles in the native bile using an eluting buffer containing 10 mM sodium cholate. The percent of total cholesterol carried in vesicles in gallbladder bile of stone patients was significantly greater than that in control patients. Total cholesterol concentration in gallbladder bile of stone patients was significantly greater than in controls. This difference was due to the fact that vesicular cholesterol concentration was significantly greater in the gallbladder bile of stone patients compared to controls. Micellar cholesterol concentrations were similar in the two groups. Nucleation time was related significantly to vesicular cholesterol concentration in correlation analysis and, as previously shown, so was total protein concentration. This study supports the importance of vesicular cholesterol in solid crystal formation and demonstrates for the first time that the rate of cholesterol monohydrate crystal formation is directly related to the amount of cholesterol transported in vesicles.


Phenylalanyl-tRNA synthetase from E. coli MRE-600: analysis of the active site distribution on the enzyme subunits by affinity labelling.
Affinity labelling has been employed to localize the substrate-binding sites on the enzyme subunits of phenylalanyl-tRNA synthetase (L-phenylalanine:tRNAPhe-ligase, EC 126.96.36.199) of Escherichia coli MRE-600 (alpha 2 beta 2-type). N-Chlorambucilylphenylalanyl-tRNA, N-bromoacetylphenylalanyl-tRNA, tRNAPhe containing an azido group at the eighth position of the molecule (S4U), tRNAPhe containing azido groups at different points of the molecule, p-azidoanilidate of phenylalanine, adenosine 5'-trimethaphosphate and N-bromoacetyl-L-phenylalaninyladenylate were used in experiments. It has been shown that tRNA-binding sites are formed on heavy beta-subunits of the enzyme. Phenylalanyl-tRNA is also localized on beta-subunits, while the aminoacyl moiety of aminoacyl-tRNA is localized near the contact region of subunits. The phenylalanine-binding site is located on light alpha-subunits of the enzyme. Adenosine 5'-trimethaphosphate and the analogue of phenylalanyladenylate modify both types of enzyme subunits. In our opinion, the catalytic center of tRNA aminoacylation is formed in the contact region of subunits, and the aminoacyl moiety is transferred into tRNA (from the alpha- into beta-subunit in the region of their contact).


[Subgaleal hematoma in 2 neonates].
Subgaleal hematoma in the newborn infant is rare, occurs early, and often bears serious consequences. We report on 2 subacute cases of bruising of the scalp that occurred following the use of a suction cup. Emergency treatment consisted of a transfusion of packed red blood cells and fresh frozen plasma. Children born by use of vacuum extractor or forceps require careful monitoring by the nursing staff throughout their stay in the maternity unit.


IgA-induced chemokinesis of human polymorphonuclear neutrophils: requirement of their Fc-alpha receptor.
The influence of purified human immunoglobulins on the migration of human neutrophils (PMN) was measured in a 48-well micro chemotaxis chamber, with results expressed as percentages of maximal formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated chemotaxis. Both monomeric and polymeric IgA, of both subclasses, in monoclonal and polyclonal form, as well as secretory IgA and Fc-alpha, but not Fab-alpha fragments, enhanced PMN migration when present either in the lower or in both compartments of the chamber (chemokinesis) at concns as low as 0.1 mg/ml. IgM and IgE had no such effect. In contrast, IgG was chemotactic at low concn (0.1 mg/ml). Both monomeric and polymeric IgA decreased the maximally induced FMLP-chemotaxis, but IgA increased chemotaxis induced by suboptimal levels of FMLP. Binding of 3[H]-FMLP to PMN was not affected. Cytofluorographic analysis revealed that, under the conditions of the assay, IgA did bind to 93% of PMN. Thus, the various forms of IgA have a dual effect on human PMN mobility: (1) increase PMN random migration (chemokinesis); and (2) decrease the maximal FMLP-induced chemotaxis. Our data support the requirement of binding of IgA to the Fc-alpha receptor of PMN for expression of these activities. This effect of IgA on PMN mobility may be relevant in IgA deficiency states.


Undergraduate plastic surgery in the United Kingdom: The students' perspective.
Plastic Surgery is consistently ranked as one of the most competitive for higher surgical training in the United Kingdom. With falling rates of undergraduate Plastic Surgery education there is a danger that potentially excellent candidates will be deterred from applying for training positions. We sought to investigate a cohort of UK medical students with an established interest in Plastic Surgery regarding the factors that influence their interest in the specialty. A cross-sectional study design was used with questionnaires distributed to medical students attending the BAPRAS Undergraduate Day in London and Glasgow University Plastics Undergraduate National Conference in 2019. The questionnaire included factors attracting and deterring them from a career in Plastic Surgery, alongside their undergraduate exposure to the specialty and suggestions on how it could be improved. The most common factors attracting students to a career in Plastic Surgery were variety (25%), surgical intricacy (15%) and immediate effect on patient quality of life (12%). The most common factors deterring students from a Plastic Surgery career were a competitive national selection process (41%), work-life balance (15%) and length of training (12%). As 47% of students had not received undergraduate education in Plastic Surgery, their perceptions of the specialty will be likely be influenced from external, often negative, sources such as television and other media. To safeguard the future Plastic Surgery workforce, universities should collaborate with local departments and professional bodies to meet the needs of medical students for undergraduate exposure through mentorship, workshops, taster days and clinical placements.


IGF2BP1 silencing inhibits proliferation and induces apoptosis of high glucose-induced non-small cell lung cancer cells by regulating Netrin-1.
Non-small cell lung cancer (NSCLC) accompanied by diabetes is an important risk factor affecting the prognosis of patients with NSCLC in clinical practice. However, the effect of high glucose (HG) in the pathogenesis of NSCLC remains elusive. It has been found that the RNA-binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) plays important roles in various diseases, including NSCLC and diabetes. The aim of this study was to explore the role of IGF2BP1 in HG-treated NSCLC cells, and further investigate its underlying molecular mechanism. Results showed that IGF2BP1 was highly expressed in HG-treated NSCLC cells. Knockdown of IGF2BP1 inhibited cancer cell proliferation, migration and invasion, as well as induced cell cycle arrest and apoptosis. Besides, IGF2BP1 silencing decreased the Netrin-1 level in HG-treated NSCLC cells. Reintroduction of Netrin-1 expression rescued IGF2BP1 deficiency-induced cell proliferation reduction, migration suppression, cell cycle arrest and apoptosis. These findings suggest that IGF2BP1 silencing inhibits the occurrence of tumor events through down-regulating Netrin-1 expression, indicating that the IGF2BP1/Netrin-1 axis exerts an oncogenic role in HG-treated NSCLC cells.


Reversible total esophageal exclusion.
A 23-year-old man with miliary tuberculosis had severe esophageal hemorrhage secondary to eroding tuberculous nodes. Balloon tamponade and packing with gauze did not alter the profuse bleeding. Empyema of the right thorax, massive mediastinal nodes, an unknown site of bleeding in the esophagus, and diffuse pulmonary involvement with tuberculosis precluded a thoracotomy. Because of widespread peritoneal tuberculosis, permanent esophageal exclusion by ligation was rejected as bowel interposition would have been extremely difficult at a later time. Reversible total esophageal exclusion was successfully utilized.


Neuro-anaesthesia: the present position.
Over the years the basic principles underlying the practice of neuroanaesthesia have not changed, but introduction of new anaesthetic agents and associated techniques have improved the ability of the neuroanaesthetist to "fine tune" the patients physiological state. This has improved the capacity of the neuroanaesthetist to mitigate the inevitable fluctuations which occur and prevent their ill effects. Further improvement is still desirable and possible. It takes years for the correct plan of usage of new drugs to be formulated for the clinical situation, and their relationships established to new techniques of patient monitoring. Like neurosurgery itself neuroanaesthesia shows no signs of approaching a final definitive state in the forseeable future.


Case Report: Erythema Nodosum and Melioidosis: An Unreported Association.
We report two cases of pediatric melioidosis. Both presented with erythema nodosum (EN) on the lower limbs. They both resided in an endemic region for this condition, and a presumptive diagnosis was made by high indirect hemagglutination assay titers of > 5,120 in both. Before this, there has been no recorded association between melioidosis and EN.


Clinicopathological characteristics of pleomorphic adenoma from the labial gland: A 20-year experience with 173 cases in one single institution.
Pleomorphic adenoma (PA) of the lip is not a common phenomenon, and existing literature provides limited information on the clinicopathological features of labial PA. Patients diagnosed with labial PA at our single institution over the past 20 years (2001-2020) was retrospectively screened and analyzed to investigate the epidemiologic and clinicopathological features of these tumors. A total of 173 cases were screened out, and the average age was 44.3 (range 7-82) years, with a peak incidence rate during the third decade. A slight predilection for men (52%) was observed, and PA occurs more frequently in the upper lip than in the lower lip, with a ratio of 14.7:1. On clinical examination, labial PAs usually present as painless masses that develop slowly with no systemic symptoms. Histologically, labial PAs contain myoepithelial and polygonal epithelial cells in myxoid, hyaline, fibrous, chondroid, and even osseous tissues, similar to those in other sites. Specifically, 15 of 173 patients with labial PA presented with cutaneous PA. Labial PA presents over a wide age range and dominantly occurs at the upper lip. Surgical resection is the major treatment strategy, and postoperative recurrence or malignant transformation of labial PA was extremely rare.


Assessment of the bioaccessibility of polycyclic aromatic hydrocarbons in soils from Beijing using an in vitro test.
As an important human exposure pathway of contaminants, soil ingestion is of increasing concern for assessing health risk from polycyclic aromatic hydrocarbons (PAHs) in soils. A wide range of total PAH concentrations ranging from 0.112 microg g(-1) to 27.8 microg g(-1) in soils collected from different public sites, including gas stations, roadsides, bus stops, a kindergarten, primary and middle schools, a university and residential area, was detected. In general, total PAHs concentrations in soils from traffic areas were significantly higher than that from the other sites, indicating a dominant contribution from motor vehicles. Physiologically based in vitro tests were used to evaluate the oral bioaccessibility of PAHs in surface soil under different land uses in Beijing regarding both gastric and small intestinal conditions. It was found that the oral bioaccessibility of total PAHs in small intestinal condition, ranging from 9.2% to 60.5% of total PAHs in soil, was significantly higher than gastric condition, ranging from 3.9% to 54.9%. The bioaccessibility of individual PAHs in soils generally decreased with the increasing ring number of PAHs in both gastric and small intestinal conditions. However, the ratio of bioaccessibility of individual PAHs in gastric condition to that in small intestinal condition, generally increased with increasing ring number, indicating the relatively pronounced effect of bile extract on improving bioaccessibility of PAHs with relatively high ring numbers characterized by their high K(ow) values. The observation that bile extract at a level higher than critical micelle concentration could reduce the surface tension of digestive juice substantially, which may cause PAHs to be available for intestinal absorption, calls for more careful establishment of reliable soil criteria for PAHs, especially concerning the health of children who may ingest a considerable amount of PAH-contaminated soil via outdoor hand-mouth activities.


Electronic Characteristics of MoSe2 and MoTe2 for Nanoelectronic Applications.
Single-crystalline MoSe2 and MoTe2 platelets were grown by Chemical Vapor Transport (CVT), followed by exfoliation, device fabrication, optical and electrical characterization. We observed that for the field-effect-transistor (FET) channel thickness in range of 5.5 nm to 8.5 nm, MoTe2 shows p-type, whereas MoSe2 with channel thickness range of 1.6 nm to 10.5 nm, shows n-type conductivity behavior. At room temperature, both MoSe2 and MoTe2 FETs have high ON/OFF current ratio and low contact resistance. Controlling charge carrier type and mobility in MoSe2 and MoTe2 layers can pave a way for utilizing these materials for heterojunction nanoelctronic devices with superior performance.


Imaging of striatal dopamine transporters in rat brain with single pinhole SPECT and co-aligned MRI is highly reproducible.
A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand (123)I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clinical MRI scanner using a specially developed surface coil. The SPECT images showed clear striatal uptake. On the MR images, cerebral and extra-cerebral structures could be easily delineated. The mean striatal to non-specific [(123)I]FP-CIT binding ratios of the test/retest studies were 1.7 +/- 0.2 and 1.6 +/- 0.2, respectively. The test/retest variability was approximately 9%. We conclude that the assessment of striatal [(123)I]FP-CIT binding ratios in rats is highly reproducible.


Patient and Surgeon Risk-Taking Regarding Total Joint Arthroplasty.
Decisions regarding care for osteoarthritis involve physicians helping patients understand likely benefits and harms of treatment. Little work has directly compared patient and surgeon risk-taking attitudes, which may help inform strategies for shared decision-making and improve patient satisfaction. We surveyed patients contemplating total joint arthroplasty visiting a high-volume specialty hospital regarding general questions about risk-taking, as well as willingness to undergo surgery under hypothetical likelihoods of moderate improvement and complications. We compared responses from surgeons answering similar questions about willingness to recommend surgery. Altogether 82% (162/197) of patients responded, as did 65% (30/46) of joint replacement surgeons. Mean age among patients was 66.4 years; 58% were female. Surgeons averaged 399 surgeries in 2019. Responses were similar between groups for general, health, career, financial, and sports/leisure risk-taking (P > .20); surgeons were marginally more risk-taking in driving (P = .05). For willingness to have or recommend surgery, as the chance of benefit decreased, or the chance of harm increased, the percentage willing to have or recommend surgery decreased. Between a 70% and 95% chance of moderate improvement (for a 2% complication risk), as well as between a 90% and 95% chance of moderate improvement (for 4% and 6% complication risks), the percentage willing to have or recommend surgery was indistinguishable between patients and surgeons. However, for lower likelihoods of improvement, a higher percentage of patients were willing to undergo surgery than surgeons recommended. Patients were also more often indifferent between complication risks. Although patients and surgeons were often willing to have or recommend joint replacement surgery at similar rates, they diverged for lower-benefit higher-harm scenarios.