Phylogenetic and pathogenic characterization of lumpy skin disease virus circulating in China.
The genomic characterization of emerging pathogens is critical for unraveling their origin and tracking their dissemination. Lumpy skin disease virus (LSDV) is a rapidly emerging pathogen in Asia including China. Although the first Lumpy skin disease (LSD) outbreak was reported in 2019, the origin, transmission, and evolutionary trajectory of LSDV in China have remained obscure. The viral genome of a circulating LSDV strain in China, abbreviated LSDV/FJ/CHA/2021, was sequenced using the next-generation sequencing technique. The morphology and cytoplasmic viral factory of these LSDV isolates were observed using transmission electron microscopy. Subsequently, the genomic characterization of this LSDV isolate was systematically analyzed for the first time using the bioinformatics software. The current study revealed that several mutations in the genome of LSDV isolates circulating in China were identified using single nucleotide polymorphisms (SNPs) analysis, an instrument to evaluate for continuous adaptive evaluation of a virus. Furthermore, phylogenomic analysis was used to identify the lineage using the whole genome sequences of 44 LSDV isolates. The result revealed that the isolates from China were closely similar to that of the LSDV isolates from Vietnam, which are divided into a monophyletic lineage sub-group I. The SNPs and Simplot analysis indicate no significant occurrence of the recombinant event on the genome of LSDV isolates in China. Notably, the live virus challenge experiment demonstrated that the pathogenic characterization of this LSDV isolate belongs to a virulent strain. Collectively, we gain the first insight into the evolutionary trajectory, spatiotemporal transmission, and pathogenic characterization of circulating LSDV in China. This study provides a unique reference for risk assessment, guiding diagnostics, and prevention in epizootic and non-epizootic areas.


[Clinical and experimental studies on composite divitriol infusion in treating tinea manum].
To investigate the effect of Composite Divitriol Infusion (CDI) in treating tinea manum and studying its antimycotic action. CDI was used to treat 139 patients with tinea manum. The experimental study in vivo was done, scanning electron microscopy (SEM) was used to observe the therapeutical effect of CDI. One hundred and four cases among the 139 patients were cured, 21 were markedly effective, 10 improved and 4 ineffective, the effective rate being 89.9%. Between CDI group and the control group, there was a very significant difference (chi 2 > 12.84, P < 0.005). The antimycotic action of CDI was studied in vitro. Its minimum inhibitory concentrations (MIC) of CDI were about 0.25% for Trichophyton rubrum, and 0.5% for Trichophyton gypseum and Microsporum gypseum. Trichophyton rubrum immersed with CDI show that the mycelia became roughened, deformed and macroconidum became smaller under SEM. CDI is valuable in treating tinea manum.


Plasma histamine concentrations in horses administered sodium penicillin, guaifenesin-xylazine-ketamine and isoflurane with morphine or butorphanol.
Various drugs administered to horses undergoing surgical procedures can release histamine. Histamine concentrations were evaluated in horses prepared for surgery and administered butorphanol or morphine intraoperative infusions. Prospective studies with one randomized. A total of 44 client-owned horses. In one study, anesthesia was induced with xylazine followed by ketamine-diazepam. Anesthesia was maintained with guaifenesin-xylazine-ketamine (GXK) during surgical preparation. For surgery, isoflurane was administered with intravenous (IV) morphine (group M: 0.15 mg kg-1 and 0.1 mg kg-1 hour-1; 15 horses) or butorphanol (group B: 0.05 mg kg-1 and 0.01 mg kg-1 hour-1; 15 horses). Histamine and morphine concentrations were measured using enzyme-linked immunoassay before opioid injection (time 0), and after 1, 2, 5, 30, 60 and 90 minutes. In a subsequent study, plasma histamine concentrations were measured in 14 horses before drug administration (baseline), 15 minutes after IV sodium penicillin and 15 minutes after starting GXK IV infusion. Statistical comparison was performed using anova for repeated measures. Pearson correlation compared morphine and histamine concentrations. Data are presented as mean ± standard deviation. Significance was assumed when p ≤ 0.05. With histamine, differences occurred between baseline (3.2 ± 2.4 ng mL-1) and GXK (5.2 ± 7.1 ng mL-1) and between baseline and time 0 in group B (11.9 ± 13.4 ng mL-1) and group M (11.1 ± 12.4 ng mL-1). No differences occurred between baseline and after penicillin or between groups M and B. Morphine concentrations were higher at 1 minute following injection (8.1 ± 5.1 ng mL-1) than at 30 minutes (4.9 ± 3.1 ng mL-1) and 60 minutes (4.0 ± 2.5 ng mL-1). Histamine correlated with morphine at 2, 30 and 60 minutes. GXK increased histamine concentration, but concentrations were similar with morphine and butorphanol.


Momentum-dependent multiple gaps in magnesium diboride probed by electron tunnelling spectroscopy.
The energy gap is the most fundamental property of a superconductor. MgB(2), a superconductor discovered in 2001, exhibits two different superconducting gaps caused by the different electron-phonon interactions in two weakly interacting bands. Theoretical calculations predict that the gap values should also vary across the Fermi surface sheets of MgB(2). However, until now, no such variation has been observed. It has been suggested that two gap values were sufficient to describe real MgB(2) samples. Here we present an electron tunnelling spectroscopy study on MgB(2)/native oxide/Pb tunnel junctions that clearly shows a distribution of gap values, confirming the importance of the anisotropic electron-phonon interaction. The gap values, and their spreads found from the tunnel junction measurements, provide valuable experimental tests for various theoretical approaches to the multi-band superconductivity in MgB(2).


Coffee drinking among Finnish youth.
The suggestion that coffee may have negative health effects has made coffee-drinking habits medically interesting. This paper reports upon coffee use among young people and describes how coffee-users differ from non-users. Data comes from questionnaires from representative nationwide samples of 12-18-year-old Finnish youth in 1977-1985. Their coffee use decreased from 1977 to 1985, and the decrease could be seen in all age and socio-demographic groups studied. In 1981, 35% of the girls and 45% of the 12-year-old boys drank coffee daily. For 18-year-olds the corresponding percentages were 67 and 75, and the mean number of cups consumed per day was 2.3 and 3.1. Compared to the non-users, the coffee-users were from lower social classes, lived more often in the countryside, and had poorer school achievement. Health-damaging habits such as smoking were more common among the coffee-users, their perceived health was somewhat poorer, and they seemed to mature earlier. The difference in regard to health disappeared after adjusting for differences in socio-demographic background and health habits. The heavy users (four cups or more a day) usually differed more from the non-users than did the moderate users (one to three cups daily).


A psychological pulse train: how young children use this cognitive framework to structure simple rhythms.
This paper examines the reproduction of both regular rhythms and irregular sequences by 5- and 7-year-old children, concentrating on the important role played by their organization around a pulse train. It is shown that: (a) the closer rhythms are to a regular beat the easier they are to reproduce and the greater are the improvements with age; (b) memory capacity is limited by the number of pulses around which the rhythm is organized rather than by the number of elements it contains; (c) all the children's productions contain two interval lengths that are in a ratio close to 1:2 and arranged in preferential sequences which we have called "stereotypes"; (d) arrhythmic sequences can only be reproduced if the intervals undergo a systematic distortion towards regularity. These results are interpreted in relation to a pulse-train hypothesis which states that on hearing a rhythm an "internal clock" or "time base" is evoked around which the rhythm is structured.


Rapid separation of phosphopeptides by microchip electrophoresis-electrospray ionization mass spectrometry.
Protein phosphorylation is a significant biological process, but separation of phosphorylated peptide isomers is often challenging for many analytical techniques. We developed a microchip electrophoresis (MCE) method for rapid separation of phosphopeptides with on-chip electrospray ionization (ESI) facilitating online sample introduction to the mass spectrometer (MS). With the method, two monophosphorylated positional isomers of insulin receptor peptide (IR1A and IR1B) and a triply phosphorylated insulin receptor peptide (IR3), all with the same amino acid sequence, were separated from the nonphosphorylated peptide (IR0) in less than one minute. For efficient separation of the positional peptide isomers from each other derivatization with 9-fluorenylmethyl reagents (either chloroformate, Fmoc-Cl, or N-succinimidyl carbonate, Fmoc-OSu) was required before the analysis. The derivatization improved not only the separation of the monophosphorylated positional peptide isomers in MCE, but also identification of the phosphorylation site based on MS/MS.


Serial Versus Direct Dilation of Small Diameter Stents Results in a More Predictable and Complete Intentional Transcatheter Stent Fracture: A PICES Bench Testing Study.
Balloon-expandable stents, implanted in infants and children with congenital heart disease (CHD), often require redilation to match somatic growth. Small diameter stents may eventually require longitudinal surgical transection to prevent iatrogenic vascular stenosis. Intentional transcatheter stent fracture (TSF) is an emerging alternative approach to stent transection, but little is known about the optimal stent substrate and best protocol to improve the likelihood of successful TSF. Bench testing was performed with a stent dilation protocol. After recording baseline characteristics, stents were serially or directly dilated using ultra-high-pressure balloons (UHPB) until fracture occurred or further stent dilation was not possible. Stent characteristics recorded were as follows: cell design, metallurgy, mechanism, and uniformity of fracture. Stents tested included bare-metal coronary stents, premounted small diameter stents, and ePTFE-covered small diameter premounted stents. Ninety-four stents representing 9 distinct models were maximally dilated, with 80 (85%) demonstrating evidence of fracture. Comprehensive fracture details were recorded in 64 stents: linear and complete in 34/64 stents (53.1%), linear and incomplete in 9/64 stents (14.1%), transverse/complex and complete in 6/64 stents (9.4%), and transverse/complex and incomplete in 15/64 stents (23.4%). Stent fracture was not accomplished in some stent models secondary to significant shortening, i.e., "napkin-ring" formation. Serial dilation resulted in evidence of fracture in 62/67 (92.5%) stents compared with 18/27 (66.7%) stents in the direct dilation group (p = 0.003). Intentional TSF is feasible in an ex vivo model. Serial dilation more reliably expanded the stent and allowed for ultimate stent fracture, whereas direct large diameter dilation of stents was more likely to generate a "napkin-ring" configuration, which may be more resistant to fracture. In vivo animal and human testing is necessary to better understand the response to attempted TSF for newly developed stents as well as those currently in use.


Antimicrobial Stewardship from Policy to Practice: Experiences from UK Antimicrobial Pharmacists.
Antimicrobial stewardship in the UK has evolved dramatically in the last 15 years. Factors driving this include initial central funding for specialist pharmacists and mandatory reductions in healthcare-associated infections (particularly Clostridium difficile infection). More recently, the introduction of national stewardship guidelines, and an increased focus on stewardship as part of the UK five-year antimicrobial resistance strategy, have accelerated and embedded developments. Antimicrobial pharmacists have been instrumental in effecting changes at an organizational and national level. This article describes the evolution of the antimicrobial pharmacist role, its impact, the progress toward the actions listed in the five-year resistance strategy, and novel emerging areas in stewardship in the UK.


Clinical profiles of cerebrovascular disorders in a population-based patient sample.
Clinical features of different types of stroke were investigated in a sample of 409 patients representative of all cases admitted for acute stroke, except subarachnoidal hemorrhages, within a well defined population. A specific cerebrovascular diagnosis was obtained by detailed clinical investigation, including CT scan. In people greater than 50 years old, men/women risk for stroke was estimated to be 1.40:1. The risk was higher in men up to the age of 80; above this age similar risk for the two genders was observed. Eleven per cent had intracerebral hemorrhage, 13% TIA, 51% non-embolic and 25% embolic brain infarction. In all diagnostic categories there were similar proportions of patients who had a history of hypertension and previous stroke, neither did hemoglobin and hematocrit levels differ between the different stroke disorders. TIA preceded intracerebral hemorrhage in 11% and brain infarction in 15-20%. As opposed to patients with ischemic lesions, subjects with intracerebral hemorrhage had higher systolic blood pressure levels and more severe symptoms on admission to hospital. Ischemic stroke was associated with male predominance, different ischemic manifestations of heart diseases and diabetes.


Questioning the "big assumptions". Part II: recognizing organizational contradictions that impede institutional change.
Well-designed medical curriculum reforms can fall short of their primary objectives during implementation when unanticipated or unaddressed organizational resistance surfaces. This typically occurs if the agents for change ignore faculty concerns during the planning stage or when the provision of essential institutional safeguards to support new behaviors are neglected. Disappointing outcomes in curriculum reforms then result in the perpetuation of or reversion to the status quo despite the loftiest of goals. Institutional resistance to change, much like that observed during personal development, does not necessarily indicate a communal lack of commitment to the organization's newly stated goals. It may reflect the existence of competing organizational objectives that must be addressed before substantive advances in a new direction can be accomplished. The authors describe how the Big Assumptions process (see previous article) was adapted and applied at the institutional level during a school of medicine's curriculum reform. Reform leaders encouraged faculty participants to articulate their reservations about considered changes to provided insights into the organization's competing commitments. The line of discussion provided an opportunity for faculty to appreciate the gridlock that existed until appropriate test of the school's long held Big Assumptions could be conducted. The Big Assumptions process proved useful in moving faculty groups to recognize and questions the validity of unchallenged institutional beliefs that were likely to undermine efforts toward change. The process also allowed the organization to put essential institutional safeguards in place that ultimately insured that substantive reforms could be sustained.


A new enantiomerization mechanism for tripodal penta-coordinate Zn(II)(nta) complexes. Theoretical clarification of the observed 1H NMR spectrum.
Based on DFT calculations (RB3LYP/LANL2DZp), the unexpected single-line 1H NMR spectrum of Zn(II)(nta), nta = 2,2',2''-nitrilotriacetate, can be ascribed to a non-dissociative enantiomerization process (deltadeltadelta<=>lambdalambdalambda) from C3viaC3v to C3 symmetry. The energy barrier is rather low and depends to a lesser extent on the nature of the co-ligand in [Zn(nta)X]2- (X: H-, CH3- NH2-, OCH3-, F-, Cl-, Br-, I-) and [Zn(nta)Y]- (Y: NCH, CO, N2, O(CH3)2), but more so on the overall charge of the complex. The energy barrier for enantiomerization of [Zn(nta)X]2- is between 5.7 and 6.7 kcal mol-1, and for [Zn(nta)Y]- between 2.2 and 3.1 kcal mol-1.


Dual aminoquinolate diarylboron and nickel catalysed metallaphotoredox platform for carbon-oxygen bond construction.
Herein, aminoquinolate diarylboron complexes are utilized as photocatalysts in dual Ni/photoredox catalyzed carbon-oxygen construction reactions. Via this unified metallaphotoredox platform, diverse (hetero)aryl halides can be conveniently coupled with acids, alcohols and water. This method features operational simplicity, broad substrate scope and good compatibility with functional groups.


Selection of a spectral analysis method for the assessment of velocity distribution based on the spectral distribution of ultrasonic Doppler signals.
The direct Fourier transform method, autoregressive modelling, the maximum likelihood method and the Wigner-Ville distribution were applied to the Doppler signal obtained from a fully insonated laminar model flow. The appreciation of the spectral method was based on the properties of the ratio variance/(fmean)2 (INT) of the spectrum. The basic criterion was the sensitivity of INT to the analysis parameters, especially the data window. The results of spectral analysis, as well as the properties of INT, were strongly affected by the method applied. The maximum likelihood method appeared best suited for the purpose of assessment of velocity distribution and is expected to give the best results in the case of in vivo blood flow. The performances of other discussed methods were inferior, due to their stronger incompatibility with the signal properties.


Combining reverse-transcription multiplex PCR and microfluidic electrophoresis to simultaneously detect seven mosquito-transmitted zoonotic encephalomyelitis viruses.
Several mosquito-transmitted viruses are causative agents for zoonotic encephalomyelitis. Rapid identification of these viruses in mosquito populations is an effective method for surveying these diseases. To detect multiple mosquito-transmitted viral agents, including West Nile virus, Saint Louis encephalitis virus, Venezuelan equine encephalomyelitis virus, Western equine encephalomyelitis virus, Eastern equine encephalomyelitis virus, Highlands J virus and Japanese encephalitis virus, an assay using multiplex reverse-transcription PCR combined with microfluidic electrophoresis was developed and evaluated. Tailed nested primers were used in the assay to amplify specific viral genomic segments, and products with specific length were further analyzed by using a microfluidic electrophoresis chip. The assay exhibited good specificity and analytical sensitivity (10(2) copies/µL). This technology can be helpful in the quarantine and surveillance of exotic encephalomyelitis viruses which are transmitted by mosquitoes.


[Surgical therapy of the kinking of the internal carotid artery. Indications and limitations].
Surgical treatment of a case of symptomatic kinking of the internal carotid suggested a review of the problem on the basis of the national and international literature. Opinions are not only extremely distant but not infrequently antithetical. In such a heterogeneous subjects that is often difficult to interpret, the most interesting approaches are examined in the light of new experimental and clinical findings.


[Preliminary study on extensive amplification of human dendritic cells differentiated from cord blood CD34+ progenitor cells by two-step culture].
To Explore a two-step culture system to generate a large number of dendritic cells (DC) differentiated from cord blood (CB) CD(34)(+) cells. Enriched CB CD(34)(+) cells with immunoadsorption were primarily cultured in the presence of stem cell factor (SCF), Flt-3 ligand (FL), thrombopoietin (Tpo) and interleukin-3 (IL-3) for 7 (group I), 10 (group II) or 14 days (group III) respectively, and then further cultured with GM-CSF, IL-4 and TNF-alpha for 5 - 8 days to induce DC. The expansion and cell function were evaluated by flow cytometry (FCM) and mix-lymphocyte reaction (MLR), and detection of IL-12 in the supernatant by using ELISA. The total nucleated cells with 53.39 +/- 20.59-, 307.17 +/- 119.59- and 1117.25 +/- 335.49-folds expansion could be respectively obtained after 7 - 14 days of expansion culture. After DC induction, CD(1a)(+) cells were 21.40 +/- 16.70-, 143.2 +/- 60.35- and 150.8 +/- 42.16-fold increase as compared to the initial nucleated cells. Comparing with that in group I, the CD(1a)(+) cells were much more in groups II and III; but there was no difference between the latter two groups (P > 0.05). The cultured cells in the three groups showed almost the same allo-stimulatory capability and IL-12 excretion when the second culture duration maintained 8 days, while the capability and excretion were greatly decreased when the duration shortened to 5 days (P < 0.05). A plenty of functionally mature DC could be obtained from the CD(34)(+) cells in the two-step culture system of 7 - 10 days HSC expansion followed by 8 days DC induction.


Mode of action of antiprotozoan agents. Electron transfer and oxy radicals.
Cyclic voltammetry data were obtained for most of the main classes of antiprotozoan agents, specifically, nitroheterocycles, quinones, metal complexes and derivatives, iminium-type ions, and azo compounds. The reductions were generally reversible in the range of -0.3 to -0.9 V. Catalytic production of oxidative pressure from redox cycling involving oxygen is believed to be an important mode of action by the medicinal agents. Literature data contribute support.


[Fluorescence microscopic studies of prostate cells treated with Extract. radicis urticae].
Homogeneous granules detected by fluorescent microscopy which are irregularly but diffusely superimposed on the sheets of prostate cell shows a relevant decrease in ERU-induced (Bazoton) cell areas. These results verify a reduction of biologic activity in these cells.


Microperimetry in diabetic retinopathy.
Diabetic retinopathy has an enormous impact on visual function, even before permanent visual acuity loss. Moreover, adequate functional tests are mandatory to diagnose and follow diabetic patients treated for diabetic macular edema (DME). More precisely, the visual function safety profile of any therapy for DME should be accurately investigated. Microperimetry offers the possibility to obtain an exact fundus-related quantification of retinal sensitivity, and it is changing the current approach to the functional investigation of diabetic retinopathy.


Risk factors analysis of surgical complications of hepatic hemangioma: a modified Clavien-Dindo classification-based study.
There are few studies on the risk factors of postoperative complications after surgical treatment of hepatic hemangioma (HH). This study aims to provide a more scientific reference for clinical treatment. The clinical characteristics and operation data of HH patients undergoing surgical treatment in the First Affiliated Hospital of Air Force Medical University from January 2011 to December 2020 were retrospectively collected. All enrolled patients were divided into two groups based on the modified Clavien-Dindo classification: Major group (Grade II/III/IV/V) and Minor group (Grade I and no complications). Univariate and multivariate regression analysis was used to explore the risk factors for massive intraoperative blood loss (IBL) and postoperative Grade II and above complications. A total of 596 patients were enrolled, with a median age of 46.0 years (range, 22-75 years). Patients with Grade II/III/IV/V complications were included in the Major group (n = 119, 20%), and patients with Grade I and no complications were included in the Minor group (n = 477, 80%). The results of multivariate analysis of Grade II/III/IV/V complications showed that operative duration, IBL, and tumor size increased the risk of Grade II/III/IV/V complications. Conversely, serum creatinine (sCRE) decreased the risk. The results of multivariate analysis of IBL showed that tumor size, surgical method, and operative duration increased the risk of IBL. Operative duration, IBL, tumor size, and surgical method are independent risk factors that should be paid attention to in HH surgery. In addition, as an independent protective factor for HH surgery, sCRE should attract more attention from scholars.


Carboxymethylation of (1 → 6)-α-dextran from Leuconostoc spp.: Effects on microstructural, thermal and antioxidant properties.
The carboxymethylated (1 → 6)-α-dextran (CM-dex) was synthesized by introducing carboxymethyl groups at different degrees of substitution (DS). The resulting dex1-1, dex2-1, dex3-1, and dex4-1 products had degrees of substitution of 0.57, 0.78, 1.13, and 1.25, respectively. The dex3-1 showed the highest glass transition temperature (Tg) of 215.96 °C, whereas Tg of pure dextran was 149.83 °C. TGA results indicated that the residual loss was reduced along with the increase of DS in the high-temperature region (450-600 °C). Besides, the CM-dex had stronger scavenging capacity against OH radicals but lower scavenging capacity for DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals compared to that of pure dextran. The carboxymethylation of (1 → 6)-α-dextran will extend the applications for modified dextran.


The impact of environmental parameters on microcystin production in dialysis bag experiments.
It is important to understand what environmental parameters may regulate microcystin (MC) production and congener type. To determine if environmental conditions in two hydraulically connected lakes can influence MC production and congener ratios, we incubated dialysis bags containing phytoplankton from mesotrophic/eutrophic Muskegon Lake into hypereutrophic Bear Lake (Michigan, USA) and vice versa. Strong cyanobacteria growth was observed in all dialysis bags with Bear Lake phytoplankton in July and August. Phytoplankton communities were dominated by Aphanizomenon aphanizomenoides, Microcystis wesenbergii, Limnothrix redekei. MC concentrations were correlated with M. wesenbergii and A. aphanizomenoides biovolume. MC concentrations in bags incubated in the Muskegon Lake with Bear Lake water were significantly higher than the other bags. The higher light intensity and total nitrogen concentration may have caused the increase of MC production. The MC-LR/MC-RR ratios varied with sample origin but not with lake of incubation, indicating that physical environmental factors (water temperature and turbidity) were not the reasons for different toxin production ratios. Differences in total phosphorus concentrations might be one reason for the dissimilarity of the MC-LR/MC-RR ratio between the two lakes. The higher light intensity and NO3-N concentration in Muskegon Lake are two factors contributing to an increase of MC production.


Isolation of carrot Argonaute1 from subtractive somatic embryogenesis cDNA library.
Carrot Argonaute1 (C-Ago1) was isolated from a subtractive cDNA library to obtain somatic embryogenesis related genes. C-Ago1 has three conserved domains, which are found in all other Argonautes. C-Ago1 has specific expression during somatic embryogenesis, which indicates that microRNA gene expression controlling system is required for somatic embryogenesis.


Associations of postoperative delirium with activities of daily living in older people after major surgery: A prospective cohort study.
To assess the association of postoperative delirium developed in the post-anaesthetic care unit (PACU) with older patients' ability to perform activities of daily living (ADL) during the first five postoperative days. Previous studies have focused on the association between postoperative delirium and long-term function decline, however the association between postoperative delirium and the ability to perform ADL, particularly in the immediate postoperative period, needs further investigation. A prospective cohort study. A total of 271 older patients who underwent elective or emergency surgery at a tertiary care hospital in Victoria, Australia, participated in the study. Data were collected between July 2021 and December 2021. Delirium was assessed using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The Katz Index of Independence in Activities of Daily Living (KATZ ADL) scale was used to measure ADL. ADL was assessed preoperatively and daily during the first five postoperative days. The STROBE checklist was used to report this study. Results showed that 44 (16.2%) patients developed new episode of delirium. Postoperative delirium was independently associated with decline in ADL (RR = 2.83, 95% CI = 2.71-2.97; p < 0.001). Postoperative delirium was associated with a decline in ADL among older people during the first five postoperative days. Screening for delirium in the PACU is essential to identify delirium during the early stages of postoperative period and implement a timely comprehensive plan. Delirium assessment of older patients in the PACU, and for at least the first five postoperative days, is strongly recommended. We also recommend engagement of patients in a focused physical and cognitive daily activity plan, particularly for older patients undergoing major surgery. Patients and nurses helped in data collection at a tertiary care hospital.


Silencing of LRP1 Exacerbates Inflammatory Response Via TLR4/NF-κB/MAPKs Signaling Pathways in APP/PS1 Transgenic Mice.
Activation of glial cells (including microglia and astrocytes) appears central to the initiation and progression of neuroinflammation in Alzheimer's disease (AD). The low-density lipoprotein receptor-related protein 1 (LRP1) is a major receptor for amyloid-β (Aβ), which plays a critical role in AD pathogenesis. LRP1 regulates inflammatory response by modulating the release of pro-inflammatory cytokines and phagocytosis. However, the effects of LRP1 on microglia- and astrocytic cell-mediated neuroinflammation and their underlying mechanisms in AD remain unclear. Therefore, using APP/PS1 transgenic mice, we found that LRP1 is downregulated during disease progression. Silencing of brain LRP1 markedly exacerbated AD-related neuropathology including Aβ deposition, neuroinflammation, and synaptic and neuronal loss, which was accompanied by a decline in spatial cognitive ability. Further mechanistic study revealed that silencing of LRP1 initiated neuroinflammation by increasing microgliosis and astrogliosis, enhancing pro-inflammatory cytokine production, and regulating toll-like receptor 4 (TLR4)-mediated activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Taken together, these findings indicated that LRP1 suppresses microglia and astrocytic cell activation by modulating TLR4/NF-κB/MAPK signaling pathways. Our results further provide insights into the role of LRP1 in AD pathogenesis and highlight LRP1 as a potential therapeutic target for the treatment of AD.


Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial.
Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4-6 in the per protocol (PP) population, ii) patients with GT1,2,4-6 in the intention-to-treat (ITT) population, iii) patients with GT1-6 in the PP population, and iv) patients with GT1-6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1-6 was 99.7% (n/N = 334/335; 95%CI 98.3-99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1-99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1-6 infection and compensated cirrhosis. ClinicalTrials.gov, NCT03089944. This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1-6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.


Point of care testing: transcutaneous bilirubinometry in neonates.
Physicians taking care of infants in the first days of life are often faced with neonatal jaundice, especially in an era where post-partum discharge occurs earlier and assessment of newborn bilirubinemia status is required prior to discharge. The Canadian Pediatric Society and the American Academy of Pediatrics have developed and published guidelines for the diagnosis and management of hyperbilirubinemia in newborns. Point of care testing refers to any test performed outside of laboratory by clinical personnel and close to the site of patient care. Based on a summary of multiple reports during the last twenty years, we realize that devices which provide a non-invasive transcutaneous bilirubin (TcB) measurement have proven to be very useful as screening tools and provide a valid estimate of the total serum bilirubin level (TSB). Published data suggest that these devices provide measurements within 30-50 micromol/L of the TSB levels and can replace laboratory measurement particularly when TSB levels are less than 260 micromol/L. At the present time, in the literature, evidence is insufficient to abandon neonatal serum bilirubin testing and replace it with TcB. Any measurement, TSB or TcB, has potential for error. However, we have evidence that TcB, can help avoiding potential errors associated with even visual assessment of jaundice and may be useful as screening device to detect significant jaundice and decrease a large number of unnecessary skin punctures. The current manuscript is based on a careful comprehensive literature review concerning neonatal hyperbilirubinemia. We consider that this manuscript will help clinicians and laboratory professionals in the management of neonatal jaundice.


Phenytoin binding to human albumin.
Binding of phenytoin to human plasma proteins and to human serum albumin is studied using equilibrium dialysis method at pH 7.4 and 37 degrees C. Phenytoin is mainly bound to albumin, the percentage of bound drug being constant over a wide range of total drug concentrations. Calculation of the drug binding parameters show a low affinity, k = 745 M-1, and a high number of binding sites, n = 8. Palmitic acid and some acidic drugs, warfarin and phenylbutazone added to human serum albumin, decreased phenytoin binding in a non competitive way. Basic and non-ionizable drugs, on the other hand, did not modify phenytoin binding.


Evolution equation for a disclination line located between the uniaxial and isotropic phases of a nematic liquid crystal.
We derive a supplemental evolution equation for a disclination line located on an interface between the uniaxial and isotropic phases of a nematic liquid crystal. This equation provides an additional kinetic relation accounting for the motion of an interfacial disclination line. In our treatment of the problem we neglect fluid motion. Our approach is based on the notion of configurational forces. To illustrate the role of our additional evolution equation, we consider two simple examples. We also identify an expression for the configurational force exerted by the uniaxial phase at the defect located on the phase interface.


Hostile interpretation bias in depression.
Research suggests an important relationship between interpretation bias, hostility and Major Depressive Disorder (MDD). Extant literature has yet to examine hostile interpretation bias in clinically depressed samples; the current studies sought to fill this gap. Study 1 participants included undergraduates who met criteria for MDD (n=36) or no anxiety or mood diagnosis (n=35). Each participant completed a structured clinical interview along with measures of depression, hostile interpretation bias, and trait hostility. In Study 2, a sample of treatment-seeking individuals with elevated trait anger completed measures of depression, hostile interpretation bias, and trait anger. Study 1 demonstrated that, relative to the non-depressed group, individuals with depression displayed greater hostile interpretation bias but comparable levels of trait hostility. In Study 2, greater hostile interpretation bias was associated with greater depressive symptoms, and this relationship was independent of co-occurring trait anger. The correlational nature of these studies precludes interpretation of causal relationships between constructs. Additionally, replication of these results should be sought in a larger, more diverse sample. Overall, the findings suggest hostile interpretation bias may play a unique role in depression and could be a treatable feature of interpersonal mechanisms maintaining MDD.


Hypoacetylation of acetyl-histone H3 (H3K9ac) as marker of poor prognosis in oral cancer.
Epigenetics refers to changes in cell characteristics that occur independently of modifications to the DNA sequence. Oral carcinogenesis is influenced by modifications in epigenetic mechanisms, including changes in histones, which are proteins that support chromatin remodelling for the dynamic regulation of gene expression and silencing. The dysregulation of histone acetylation can lead to the uncontrolled activity of different genes, thereby triggering events associated with malignant transformation. The aim of this study was to analyse the expression of acetyl-histone H3 at lys9 (H3K9ac) in oral leucoplakia (OL) and oral squamous cell carcinoma (OSCC) in addition to its association with cell proliferation, epithelial-mesenchymal transition (EMT) and clinical-pathological findings. Samples of normal oral mucosa (NOM), OL and OSCC were submitted to immunohistochemical analysis using anti-H3K9ac, Ki67 and vimentin. Slides were submitted to quantitative analysis regarding the percentage of positive cells. OSCC presented less expression of H3K9ac in comparison to OL (P < 0.01), whereas Ki67 and vimentin levels increased from OL to OSCC (P < 0.001 and P = 0.03, respectively). OSCC patients with poor prognosis had less H3K9ac expression (P = 0.04). The Kaplan-Meier cumulative survival curves also revealed lower survival rates in patients with less H3K9ac expression (P < 0.01). The present findings suggest that changes in H3K9ac occur during the process of oral carcinogenesis along with an increase in cell proliferation and EMT. The results demonstrate that H3K9ac may be a useful novel prognostic marker for OSCC.


Influence of amine-modified poly(vinyl alcohol)s on vibrating-membrane nebulizer performance and lung toxicity.
A suitable aerosol droplet size and formulation output rate is essential for the therapy of lung diseases under application of nebulizers. The current study investigated the potential of amine-modified poly(vinyl alcohol)s as excipients for inhalation delivery. A change of conductivity (effective at <0.1mg/ml) and viscosity (effective at >0.1mg/ml) of samples that were supplemented with charge-modified polymers had a significant influence on the generated droplet size (shift from ~8 to ~4 μm) and formulation throughput rate (shift from ~0.2 to ~1.0 g/min), where polymers with a higher amine density (and molecular weight) showed an elevated activity. Biocompatibility assessment of polymers in A549 cells and an isolated lung model resulted in cell lysis and lung edema formation dependent on the type (degree of amine substitution) and dose of polymer applied. Suitable compositions and concentrations of amine-modified poly(vinyl alcohol)s were identified with respect to an optimized nebulizer performance and acceptable biocompatibility. Charge-modified polymers represent novel excipients with potential to improve inhalation therapy.


Inhibition of human periodontal prostaglandin E2 synthesis with selected agents.
Considerable evidence has demonstrated the importance of PGE2 synthesis in the pathogenesis of periodontal disease. Although various cyclooxygenase inhibitors have been known to block periodontal PGE2 synthesis and prevent disease progression in animal models, there are few reports comparing relative efficacies of various inhibitors of arachidonic acid (ARA) metabolism. We have developed a sensitive in vitro assay to measure PGE2 synthesis in periodontal tissues. The apparent IC50 values (i.e. the concentration of drug which causes 50% inhibition of maximum PGE2 synthesis) have been determined for a series of arachidonic acid analogues as well as competitive and non-competitive cyclooxygenase inhibitors. Periodontal tissue homogenates were incubated in the presence of 3H-arachidonic acid for 45 min at 37 degrees C. Inhibitors were tested at 10(-10)-10(-4) M and at zero concentration to measure conversion of 3H-arachidonate to 3H-PGE2. Log or half log dilutions of inhibitors were tested in triplicate for each assay. Radiolabeled PGE2 was extracted from homogenates, purified by reverse phase chromatography and quantitated by double antibody capture. RIA was performed on each homogenate to determine the amount of endogenous unlabeled PGE2 present in the sample to correct for antibody capture recovery. The apparent IC50 values were determined for each drug by averaging two or more replicate assays. Specific total enzymatic activity of periodontal tissue homogenates was typically 5-11 pg PGE2/min/mg tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


Conditional expression of microRNA against E-selectin inhibits leukocyte-endothelial adhesive interaction under inflammatory condition.
Human E-selectin, an endothelial adhesion molecule, is induced in the brain arteries by cerebral ischemia and participates in the infiltration of leukocytes that cause inflammatory reaction leading to brain damage. To prevent leukocyte infiltration in the brain, we designed gene therapeutic constructs to suppress E-selectin expression. The constructs were composed of microRNAs (miR-E1 and miR-E2) complementary to the human E-selectin cDNA, which were directed by a minimum cis-element of the human E-selectin promoter. Transfection in human aorta endothelial cells (HAECs) with these constructs revealed that the E-selectin promoter was sufficiently activated in response to tumor necrosis factor-alpha (TNF-alpha), and miR-E1 and miR-E2 could suppress E-selectin expression resulting in the significant inhibition of leukocyte adhesion. These results suggested that the combination of the E-selectin promoter and microRNAs could allow the restricted expression of transgenes in activated endothelial cells and diminish leukocyte recruitment.


Elective surgery in times of COVID-19: A two-centre analysis of postponed operations and disease-related morbidity and mortality.
COVID-19 had an impact on the whole range of worldwide medical services. Due to the high risk of in-hospital transmission and disproportionate perioperative rates of morbidity and mortality in occult COVID-19 patients surgeons were faced with the challenging triage of surgeries into emergency, urgent and elective. The present study investigates postponed elective surgery and its impact on the medical condition of patients in two high-volume departments of general, visceral, thoracic, transplant and vascular surgery. Operations that have been postponed due to COVID-19 were recorded in the Departments of General-, Visceral-, Thoracic- and Vascular Surgery at the University Hospitals of Leipzig and Greifs-wald. Data was analysed descriptively concerning patient outcomes as well as emergency admissions and surgeries. In the Leipzig and Greifswald University Hospitals 89 and 92 elective surgeries were postponed, respectively. No patient needed an extension of surgical procedure when eventually operated. One patient with extensive obesity died early during the suspension period due to cardiac complications. Four patients needed emergency admission to hospital one of whom required urgent surgery. In neither of the two surgical departments did a patient acquire a nosocomial infection with COVID-19. While medical consequences of COVID-19 seem multidimensional and severe, our data indicate that the short-term postponement of elective surgery did not cause an unproportional increase of morbidity and mortality. Although the restrictions may have been fear-driven, given no confirmed cases and thus no concrete risk of infection, the early and well-coordinated action may have provided protection from uncontrolled interruption of medical services by loss of medical workforce or capacity. Well-organized and early suspension of elective surgery had no disproportionate impact on patient outcomes while averting nosocomial transmission of COVID-19.


Validation of a method for collecting annual, population-based oral health data for the MCH Title V Block Grant.
This study sought to determine whether estimates of oral health-related indicators generated using a relatively small purposive sample of schools were reasonable. We collected and analyzed data from two open-mouth school oral health surveys conducted in Ohio in 2004-2005. In each survey, data were gathered for nine indicators using direct observation and a questionnaire. The first survey used unweighted data from 23 sentinel schools purposively selected to represent the state based on the findings of a large 1998-1999 oral health survey (337 schools). The second survey used weighted data aggregated from 374 schools randomly selected to represent each of Ohio's 88 counties. The point estimates from the first data set were compared with 95% confidence intervals (CIs) from the second and Chi-square measures were estimated to determine statistically significant differences. For six of nine indicators, point estimates for the sentinel schools fell within the relatively narrow 95% CIs generated for the 374 schools sampled at the county level. Only one indicator (history of tooth decay) was found to be significantly different according to Chi-square analysis. Ohio's sentinel schools approach provided reasonable estimates suitable for annual reporting as required for the Title V Maternal and Child Health Block Grant. Data collected in this manner are likely to be reasonable population estimates and less costly than larger surveys.


Unsteady nanofluid flow over a cone featuring mixed convection and variable viscosity.
This article addresses unsteady nanofluid flow over a cone with MHD and mixed convection effects. Effects of variable viscosity and viscous dissipation are also considered. The resulting system of equations is tackled through the Homotopy Analysis Method (HAM). The impact of different influential variables on skin friction coefficient, heat and mass flux are discovered through numerical tables and graphs. It is noted that the surface drag force in x and y directions increases against the buoyancy force parameter. Also, it is observed that the tangential and azimuthal velocity decrease against the variable viscosity parameter. Furthermore, the temperature of fluid is observed to decay against the unsteady parameter but it increases against the Eckert number.


Identification of HIV-1 genitourinary tract compartmentalization by analyzing the env gene sequences in urine.
HIV-1 persists indefinitely in memory CD4 T cells and other long-lived cellular reservoirs despite antiretroviral therapy. Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that the kidney represents a separate compartment for HIV-1 replication. Here, to better understand the viruses in this unique site, we genetically characterized and compared the viruses in blood and urine specimens from 24 HIV-1 infected patients with detectable viremia. Blood and urine samples were obtained from 35 HIV-1 positive patients. Single-genome amplification was performed on HIV-1 env RNA and DNA isolated from urine supernatants and urine-derived cell pellets, respectively, as well as from plasma and peripheral blood mononuclear cell from the same individuals. Neighbor-joining trees were constructed under the Kimura 2-parameter model. We amplified and sequenced the full-length HIV-1 envelope (env) gene from 12 of the 24 individuals, indicating that 50% of the viremic HIV-1-positive patients had viral RNA in their urine. Phylogenetic analysis of the env sequences from four individuals with more than 15 urine-derived env sequences showed that the majority of the sequences from urine formed distinct cluster(s) independent of those peripheral blood mononuclear cell and plasma-derived sequences, consistent with viral compartmentalization in the urine. Our results suggest the presence of a distinct HIV compartment in the genitourinary tract.


Exploring disease interrelationships in older inpatients: a single-centre, retrospective study.
Comorbidity is a common phenomenon in the older population; it causes a heavy burden on societies and individuals. However, the relevant evidence, especially in the southwestern region of China, is insufficient. We aimed to examine current comorbidity characteristics as well as correlations among diseases in individuals aged >60 years. Retrospective study. We included records of 2,995 inpatients treated at the Gerontological Department of Sichuan Geriatric Hospital from January 2018 to February 2022. The patients were divided into groups according to sex and age. Diseases were categorised based on the International Classification of Diseases and their Chinese names. We calculated the age-adjusted Charlson Comorbidity Index (ACCI), categorised diseases using the China Health and Retirement Longitudinal Study questionnaire, and visualised comorbidity using web graphs and the Apriori algorithm. The ACCI was generally high, and it increased with age. There were significant differences in the frequency of all diseases across age groups, especially in individuals aged ≥90 years. The most common comorbid diseases were liver diseases, stomach or other digestive diseases, and hypertension. Strong correlations between the most common digestive diseases and hypertension were observed. Our findings provide insights into the current situation regarding comorbidity and the correlations among diseases in the older population. We expect our findings to inform future research directions as well as policies regarding general clinical practice and public health, especially for medical consortiums.


Contractions induced by sodium withdrawal in crab (Callinectes danae) muscle fibres.
A study was made of the effects of Na removal on the resting tension of single muscle fibres of the crab Callinectes danae. Reduction of [Na]o (replacement with Li, Tris or choline) below a threshold value, typical for each fibre, induced spontaneous, local contractions randomly dispersed along the fibres; this was followed by propagated contractile waves and tension oscillations. Sustained contractures were occasionally seen at threshold [Na]o and were consistently observed when [Na]o was further reduced. The Na withdrawal contractions depended on [Ca]o and were abolished in Ca-free media; they were restored within seconds after the addition of Ca (3-12 mM) or Sr (15-25 mM), but not Ba (10-100 mM), to the media. Caffeine (0.2-1.0 mM) facilitated, whereas La (2-5 mM), procaine (1 mM) or lidocaine (10 mM) inhibited the Na-withdrawal contractions. It is concluded that increased Ca influx across the sarcolemma and release of stored Ca from the sarcoplasmic reticulum are involved in the contractions induced by Na-deficient solutions in crab fibres.


CD166-specific CAR-T cells potently target colorectal cancer cells.
Chimeric antigen receptor (CAR) T-cell therapy is emerging as an effective cancer treatment, such as for hematological malignancies, however its effectiveness as an approach to treat solid tumors, such as in colorectal cancer (CRC), remains to be better developed. One area of intense development has been in the identification and characterization of novel cancer-related ligand receptors for CAR design and evaluation. It is known that the CD6 receptors CD166 and CD318 are highly expressed in CRC, and several CAR-Ts have also been explored in preclinical and clinical studies for the treatment of CRC, with promising safety and efficacy findings. Here, we constructed a CAR based on the extracellular domain of CD6 and demonstrate its cytotoxic effect in target positive human CRC cell lines. Unexpectedly, we found that CD6-CAR-T cells targeted CD166 instead of CD318. Furthermore, CD6-CAR-T cells show robust cytotoxicity to CD166-positive cell lines in a dose-dependent manner with cytokine IFN-γ significantly released. Particularly, CD6-CAR-T cells show potent cytotoxicity targeting CRC cancer stem cells (CSCs), highlighting that CD6-CAR-T is a promising approach for the therapy of CRC.


Isolation and characterization of a resistant core peptide of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF); confirmation of the GM-CSF amino acid sequence by mass spectrometry.
A trypsin-resistant core peptide of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was isolated and analyzed by high-energy Cs+ liquid secondary-ion (LSI) mass spectrometric analysis. This analysis provided successful detection of the high-mass disulfide-linked core peptide as well as information confirming the existence of disulfide pairing. Similarly, LSI mass spectrometric analysis of the peptide fragments isolated chromatographically from a Staphylococcus aureus V8 protease digest of rhGM-CSF provided rapid confirmation of the cDNA-derived sequence and determination of the existing disulfide bonds between cysteine residues 54-96 and 88-121. Electrospray ionization mass spectrometry was employed to measure the molecular weight of the intact protein and to determine the number of the disulfide bonds in the protein molecule by comparative analysis of the protein before and after reduction with beta-mercaptoethanol.


Structural basis of nucleosome-dependent cGAS inhibition.
Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory diseases, and cancer. By contrast, cGAS reactivity against self-DNA in the nucleus is suppressed by chromatin tethering. We report a 3.3-angstrom-resolution cryo-electron microscopy structure of cGAS in complex with the nucleosome core particle. The structure reveals that cGAS uses two conserved arginines to anchor to the nucleosome acidic patch. The nucleosome-binding interface exclusively occupies the strong double-stranded DNA (dsDNA)-binding surface on cGAS and sterically prevents cGAS from oligomerizing into the functionally active 2:2 cGAS-dsDNA state. These findings provide a structural basis for how cGAS maintains an inhibited state in the nucleus and further exemplify the role of the nucleosome in regulating diverse nuclear protein functions.


Outcome of monochorionic diamniotic twin pregnancies followed at a single center.
We aim to evaluate the outcome of a cohort of monochorionic diamniotic twin pregnancies followed from the first trimester onwards at a single center. This was a retrospective analysis of prospectively collected data from a series of 300 monochorionic diamniotic twin pregnancies referred to our twin clinic between 2001 and 2012. Pregnancies were followed from the first trimester and fortnightly after 16 weeks of gestation. Data on pregnancy and neonatal outcome were analyzed. There were two surviving infants in 259/300 (86.4%) pregnancies, one survivor in 22/300 (7.3%) and no survivors in 19/300 (6.3%) with an overall mortality of 60/600 (10%). Twin-twin transfusion syndrome was diagnosed in 33 cases (11%), isolated intertwin weight discordance ≥ 25% in 35 (11.6%) and major congenital structural anomalies in ten (3.3%). After 32 weeks, the prospective risk of spontaneous fetal intrauterine death was one in 248 (0.4%) per pregnancy. Despite specific prenatal fetal monitoring and management, monochorionic diamniotic twin pregnancies have still to be considered at high risk of mortality, although the prospective risk of intrauterine death after 32 weeks is low. Twin-twin transfusion syndrome and congenital anomalies were the main risk factors for mortality.


[Prevalence of contact sensitization in the general population and in patch tested patients].
Contact sensitization is a common condition. The spectrum of the most important allergens may change over the course of time owing to changes in exposure. Using the so-called baseline series, a collection of the most important and frequent allergens, both population-related and clinical epidemiological studies have been performed. Basic epidemiological concepts and special aspects regarding the epidemiology of contact allergies are presented. A concise adaptation of textbook knowledge and a selective literature search were performed. On the population level, about 25% of people are sensitized to at least one substance included in the baseline series, by far most often to nickel. In view of a prevalence of around 4%, fragrances are important contact allergens, too, along with preservatives. Among patients patch tested for suspected allergic contact dermatitis, the ranking of the most important allergen groups is similar, but the prevalences are (much) higher. Short-term changes in exposure and subsequently in the spectrum of major contact allergens can best be illustrated by clinical surveillance based on routinely collected data and, if needed, preventive measures can be initiated. In addition to time trend analyses, subgroup analyses may offer important clues regarding the identification of sensitizing and eliciting exposures, respectively.


Strong modulation of plasmons in Graphene with the use of an Inverted pyramid array diffraction grating.
An optical device configuration allowing efficient electrical tuning of surface plasmon wavelength and absorption in a suspended/conformal graphene film is reported. An underlying 2-dimensional array of inverted rectangular pyramids greatly enhances optical coupling to the graphene film. In contrast to devices utilising 1D grating or Kretchman prism coupling configurations, both s and p polarization can excite plasmons due to symmetry of the grating structure. Additionally, the excited high frequency plasmon mode has a wavelength independent of incident photon angle allowing multidirectional coupling. By combining analytical methods with Rigorous Coupled-Wave Analysis, absorption of plasmons is mapped over near infrared spectral range as a function of chemical potential. Strong control over both plasmon wavelength and strength is provided by an ionic gel gate configuration. 0.04eV change in chemical potential increases plasmon energy by 0.05 eV shifting plasmon wavelength towards the visible, and providing enhancement in plasmon absorption. Most importantly, plasmon excitation can be dynamically switched off by lowering the chemical potential and moving from the intra-band to the inter-band transition region. Ability to electrically tune plasmon properties can be utilized in applications such as on-chip light modulation, photonic logic gates, optical interconnect and sensing applications.


Skp2 expression is associated with high risk and elevated Ki67 expression in gastrointestinal stromal tumours.
Gastrointestinal stromal tumors (GIST) exhibit an unpredictable clinical course and can rapidly progress to lethality. Predictions about the biological behavior of GIST are based on a number of canonical clinical and pathologic parameters whose validity in distinguishing between a benign and a malignant tumour is still imperfect. The aim of our study was to investigate the role of morphologic parameters and expression of cells cycle regulators as prognosticators in GIST. We performed an immunohistochemical analysis for Ki67, p27Kip1, Jab1, and Skp2, on a Tissue Microarray (TMA) containing 94 GIST. Expression of the above proteins was correlated to classically used prognosticators, as well as to risk groups. Clinical significance of histologic and immunohistochemical features were evaluated in 59 patients for whom follow-up information was available. Overexpression of Ki67 and Skp2, and p27Kip1 loss directly correlated with the high risk group (p = 0.03 for Ki67 and Skp2, p = 0.05 for p27Kip1). Jab1 expression did not exhibit correlation with risk. In 59 cases provided with clinical follow-up, high cellularity, presence of necrosis, and Ki67 overexpression were predictive of a reduced overall survival in a univariate model. The same parameters, as well as mitotic rate, tumour size, and p27Kip1 loss were indicative of a shortened relapse free survival interval. High cellularity, and high mitotic rate retained their prognostic significance by multivariate analysis. Our data suggest that a number of histologic parameters in combination with immunohistochemical expression of cell cycle regulators can facilitate risk categorization and predict biologic behavior in GIST. Importantly this study demonstrates, for the first time, that Skp2 expression correlates with Ki67 expression and high risk in GIST.


Bridging the gap: linking morpho-functional traits' plasticity with hyperaccumulation.
Plant species exhibiting heavy metal tolerance are instrumental in phytoremediation of metalliferous sites. Most of the time, variations in plant functional traits (PFTs) are overlooked while identifying hyperaccumulators. However, investigating morphological, physiological, and phenological variations can contribute to our knowledge about stress tolerance, and aid in identifying potential hyperaccumulators. In the present study, we investigated variation in morpho-functional traits in Solanum nigrum, a known hyperaccumulator, under lead (Pb) stress. Twenty-one PFTs including 9 above-ground (leaf count, leaf area, specific leaf area, leaf dry matter content, leaf thickness, leaf dry mass, shoot length, stem dry mass, stem diameter), 3 below-ground (root length, root dry mass, and root diameter), 4 reproductive (flower bud count, fruit count, flower count, and fruit dry mass), and 5 photosynthetic traits (total chlorophyll, total carotenoid, chlorophyll a, chlorophyll b, and photosynthetic efficiency) under varying Pb concentrations (500-2000 mg kg-1) were assessed. Pillai's trace test (MANOVA) depicted significant variations in above-ground, below-ground, and photosynthetic traits, whereas reproductive traits did not vary significantly with progressive metal concentration. However, most of the studied traits except flower count, fruit dry mass, and chlorophyll b varied significantly under Pb stress. The study depicts that enhanced PFT's plasticity enables S. nigrum to grow in Pb-contaminated soil effectively without impacting plant fitness. Plasticity of morpho-functional traits, therefore, establishes itself as a resourceful approach in successful identification of phytoremediation capacity of a plant.


Uptake of Plasmodium chabaudi hemozoin drives Kupffer cell death and fuels superinfections.
Kupffer cells (KCs) are self-maintained tissue-resident macrophages that line liver sinusoids and play an important role on host defense. It has been demonstrated that upon infection or intense liver inflammation, KCs might be severely depleted and replaced by immature monocytic cells; however, the mechanisms of cell death and the alterations on liver immunity against infections deserves further investigation. We explored the impact of acute Plasmodium infection on KC biology and on the hepatic immune response against secondary infections. Similar to patients, infection with Plasmodium chabaudi induced acute liver damage as determined by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. This was associated with accumulation of hemozoin, increased of proinflammatory response and impaired bacterial and viral clearance, which led to pathogen spread to other organs. In line with this, mice infected with Plasmodium had enhanced mortality during secondary infections, which was associated with increased production of mitochondrial superoxide, lipid peroxidation and increased free iron within KCs-hallmarks of cell death by ferroptosis. Therefore, we revealed that accumulation of iron with KCs, triggered by uptake of circulating hemozoin, is a novel mechanism of macrophage depletion and liver inflammation during malaria, providing novel insights on host susceptibility to secondary infections. Malaria can cause severe liver damage, along with depletion of liver macrophages, which can predispose individuals to secondary infections and enhance the chances of death.


Prescribing patterns of antihypertensive medications: A systematic review of literature between 2010 and 2020.
Hypertension has affected over 1.13 billion people worldwide in 2015 and it's one of the most preventable risk-factors for morbidity and mortality. Antihypertensives significantly reduce cardiovascular risks. Several studies on antihypertensives' prescribing patterns were conducted worldwide, and guidelines were developed on hypertension management. However, no systematic reviews were conducted globally to synthesize the evidence from these studies. This review aims to evaluate antihypertensives' prescription patterns, and adherence to international guidelines for hypertension management worldwide. Full-text antihypertensives' prescribing patterns evaluation studies were included. Reviews, commentaries, guidelines, and editorials were excluded. Various databases were searched including PubMed, Embase, and others. Studies were limited to English only and to articles published from (01/01/2010) to (20/03/2020). Crowe Critical Appraisal Tool (CCAT) was used for quality assessment. The most commonly prescribed antihypertensives as monotherapy in adult patients with no comorbidities were ACEIs/ARBs (Angiotensin converting enzyme inhibitors/Angiotensin receptor blockers), followed by CCBs (Calcium channel blockers), and BBs (Beta Blockers). Most commonly prescribed dual combinations were thiazide diuretics+ACEIs/ARBs, BBs + CCBs and CCBs+ACEIs/ARBs. Among diabetic patients, the most common agents were ACEIs/ARBs. Among patients with heart diseases, CCBs were prescribed frequently. While patients with kidney diseases, CCBs and ARBs were most prescribed. Of the 40 studies included in the review, only four studies directly assessed the prescribing patterns of antihypertensives in adherence to clinical practice guidelines. And only two studies confirmed adherence to guidelines. Furthermore, the quality of the majority of studies was moderate (50%), while 25% of articles were reported as either high or low quality. This review revealed that there are areas for improvement for prescribing practices of antihypertensives in concordance with the latest evidence and with clinical practice guidelines.


Hemodynamic significance of the length of a coronary arterial narrowing.
The hemodynamic significance of the length of a coronary arterial narrowing is unclear. Accordingly, the influence of the length of a given coronary narrowing on coronary hemodynamic responses was studied in 14 dogs. Recordings were made as short fixed diameter reductions were progressivley lengthened to 5, 10 and 15 mm by the addition of plastic occluders. Resting coronary blood flow decreased and pressure gradients developed across short (snare) narrowings greater than 80 percent (critical stenosis). Short 40 to 60 percent narrowings had no significant resting hemodynamic influence, but increasing their length to 10 and 15 mm consistently resulted in significant pressure gradients and flow reductions. Reactive hyperemic coronary blood flow expressed as repayment of flow debt (after 10 seconds of coronary occlusion) decreased progressively as these narrowings were lengthed. The effect of 15 mm long narrowings on resting and reactive hyperemic flows was similar to that of short 90 percent narrowings. These data indicate that there is uncertainty about the significance of coronary diameter reductions previously considered hemodynamically unimportant. In our studies, significant changes in resting and reactive hyperemic coronary flows and resting pressure gradients occurred as the length of a given degree of narrowing was increased.


Asymptotic behavior of an epidemic model with infinitely many variants.
We investigate the long-time dynamics of a SIR epidemic model with infinitely many pathogen variants infecting a homogeneous host population. We show that the basic reproduction number [Formula: see text] of the pathogen can be defined in that case and corresponds to a threshold between the persistence ([Formula: see text]) and the extinction ([Formula: see text]) of the pathogen population. When [Formula: see text] and the maximal fitness is attained by at least one variant, we show that the systems reaches an endemic equilibrium state that can be explicitly determined from the initial data. When [Formula: see text] but none of the variants attain the maximal fitness, the situation is more intricate. We show that, in general, the pathogen is uniformly persistent and any family of variants that have a fitness which is uniformly lower than the optimal fitness, eventually gets extinct. We derive a condition under which the total pathogen population converges to a limit which can be computed explicitly. We also find counterexamples that show that, when our condition is not met, the total pathogen population may converge to an unexpected value, or the system can even reach an eternally transient behavior where the total pathogen population between several values. We illustrate our results with numerical simulations that emphasize the wide variety of possible dynamics.


The mechanism of low-dose radiation-induced upregulation of immune checkpoint molecule expression in lung cancer cells.
This study explored the effect of low-dose radiation on the expression of immune checkpoint molecules in lung cancer cells and its mechanism, as well as the antitumour effect of combined low-dose radiation and immune checkpoint inhibitors. Western blot analysis was used to assess the expression of the immune checkpoint molecules CD47, PD-L1, FGL-1 and CD155 in lung cancer cells after radiation. Western blotting was also used to explore changes in the JAK2/STAT3 pathway. CD8+ T lymphocyte infiltration in tumour tissues were assessed by immunohistochemistry in a mouse model. The inhibitory effect of low-dose radiation combined with PD-L1 or CD47 inhibitors on tumor growth was evaluated by measuring tumor volume. In response to low-dose irradiation, the expression of CD47 and PD-L1 in A549 and LLC cells was increased, the expression of p-JAK2 and p-STAT3 was also increased. AG490-mediated inhibition of the JAK2/STAT3 pathway before irradiation significantly reduced the expression of p-JAK2 and p-STAT3 in lung cancer cells, in the meantime, expression of CD47 and PD-L1 was also reduced. Conventional dose exposure exhibited the same trend. PD-L1 and CD47 protein levels increased after low-dose irradiation in an LLC tumour-bearing mouse model. Low-dose irradiation combined with PD-L1 or CD47 inhibitor treatment reduced levels of PD-L1 or CD47 in tumour tissues, increased the proportion of CD8+ T lymphocytes, and significantly inhibited tumour growth. Both low-dose and regular-dose irradiation upregulate expression of the immune checkpoint molecules CD47 and PD-L1 in lung cancer cells, and the mechanism may be related to the JAK2/STAT3 pathway. Furthermore, low-dose irradiation combined with PD-L1 or CD47 inhibitors significantly inhibits tumour growth.


Objective measurement of knee laxity and stiffness with reference to knee injury diagnosis. Part 1: Design considerations and apparatus.
Apparatus capable of objectively evaluating the laxity of the knee in vivo has been developed. The equipment consisted of a microcomputer-controlled machine, into which the leg was firmly clamped. The mechanical properties of the knee were measured by slowly applying a load to the tibia, while the femur was held stationary, and monitoring the resulting displacement of the tibia. Three separate tests could be performed: anterior-posterior drawing, varus-valgus rotation and tibial rotation. The tests were carried out on both legs of each subject, making six tests in all. The forces versus displacement (or torque versus rotation) took the form of a hysteresis loop. From these a total of 24 variables describing the stiffness, laxity and visco-elastic properties of the knee were calculated.


A ratiometric fluorescent probe for sensing hypochlorite in physiological saline, bovine serum albumin and fetal bovine/calf serum.
HClO/ClO-, as one of important reactive oxygen species, is a highly reactive unavoidable by-product generated from normal cell metabolism. In recent years, efficient method for detectiing HClO/ClO- is of great important to research its pathological or physiological function in bio-systems. In this work, we have constructed a fluorescent probe (P-Hc) with ratiometric signal for sensing HClO/ClO- in aqueous solution, physiological saline and different serums based on 2-(benzo[d]thiazol-2-yl)phenol dye. The structure of P-Hc was characterized by NMR and HRMS spectrum. The sensing mechanism has also been verified by 1H NMR spectrum. The P-Hc displays good sensitivity and selectivity for HClO/ClO- with a limit of detection (LOD) of 2.03 × 10-6 M. Furthermore, P-Hc has been applied for sensing HClO/ClO- in physiological saline and different serums. Thus, P-Hc may provide a novel method for ratiometric fluorescent sensing HClO/ClO- in bio-samples.


Labeling of non poly(A) associated RNA in the rabbit cerebral cortex 24 hours after a single electroconvulsive shock.
The labeling pattern of non poly(A) associated (poly(A)-)RNA of rabbit cerebral cortex was studied 24 hr after a single electroconvulsive shock (ECS). The animals were injected subarachnoidally with [3H]uridine and sacrificed 1 hr later. The fractionation pattern of labeled nuclear poly(A)-RNA in the cerebral cortex of ECS treated animals was identical to that of the controls. However, microsomal poly(A)-RNA from the treated animals showed an increased labeling of 18S ribosomal RNA. Also 28S RNA displayed a higher labeling but the effect was not statistically significant. These results indicate a more efficient production of ribosomal RNA in the late post-ECS period which might be in relationship with an increased activity of brain protein synthesis machinery.


Haematopoiesis in the aged as studied by in vitro colony assay.
Changes occurring in human haematopoiesis with advancing age were studied using an in vitro haematopoietic colony assay in 22 elderly subjects with unexplained anaemia, and in 15 elderly and 15 young subjects without anaemia. Both elderly groups were found to have significantly lower numbers of bone marrow early erythroid-committed progenitors (BFU-E) than the young controls. The elderly anaemic group also showed significantly lower numbers of granulocyte/macrophage progenitors (CFU-GM) than the young controls. However, the responses of the erythroid-committed progenitors in the elderly groups to erythropoietin and burst-promoting activity were similar to those observed in the young controls. Therefore, it is probable that anaemia tends to occur easily in elderly individuals as a result of reduction of reserves of haematopoietic progenitors with advancing age.


2-[1-(4-tert-Butyl-phen-yl)-4,5-diphenyl-1H-imid-azol-2-yl]-4,6-di-chloro-phenol.
In the title compound, C31H26Cl2N2O, the 4,6-di-chloro-phenol and the imidazole rings are almost coplanar, with a dihedral angle of 8.89 (6)° between them and an intra-molecular O-H⋯N hydrogen bond occurs between the rings. The dihedral angles subtended by the tert-butyl-phenyl ring and the two phenyl rings with the imidazole ring are 85.18 (9), 81.22 (9) and 19.00 (8)°, respectively. The methyl groups of the tert-butyl grouping are disordered over two sets of sites in 0.589 (5):0.411 (5) ratio. In the crystal, inversion dimers linked by pairs of weak C-H⋯Cl inter-actions generate R 2 2(24) loops.


GC-MS and spectrophotometric analysis of biodegradation of new disazo dye by Trametes versicolor.
In this study; sub-tropical white rot fungi, Trametes versicolor was investigated for its ability to degrade 4-(3'-methyl-4'-(4"-nitrophenyl)azo- 1'H-pyrazol-5'-ylazo)-3-methyl- H-pyrazol-5-on in the mediums containing glucose and different concentrations of degrade dye in batch systems. This dye was synthetized at Pamukkale Universtiy of Organic Chemistry research laboratory. Samples were collected on 10 days, and was detected by Shimadzu UV-1600A spectrophotometry. Decolorization study showed that this disazo dye was removed by more than 70% in 10 days. Laccase enzyme activity was detected in samples and then last sample was analyzed by GC-MS. Metabolites weren't showed in GC-MS result. It was concluded that T. versicolor could achieve the biodegradation of this new disazo dye.


Optimal dosing of piperacillin-tazobactam for the treatment of Pseudomonas aeruginosa infections: prolonged or continuous infusion?
To compare conventional intermittent dosing regimens of piperacillin-tazobactam with prolonged and continuous infusions to determine the optimal dosing scheme against a local Pseudomonas aeruginosa population. Pharmacodynamic Monte Carlo simulation model. Microbiologic data from 470 consecutive non duplicate P. aeruginosa isolates collected from a single institution over 6 months in 2006. Five thousand simulated surgical patients and patients with neutropenia. We simulated serum concentration-time profiles at steady state for several piperacillin-tazobactam dosing regimens, including intermittent, prolonged, and continuous infusions. The probability of achieving 50% free time above the MIC against 470 P. aeruginosa isolates was calculated. The cumulative fractions of response for the intermittent-infusion regimens were 74.7% (3.375 g every 6 hrs), 79.9% (4.5 g every 6 hrs), and 85.6% (3.375 g every 4 hrs). For prolonged infusion regimens, the cumulative fractions of response were 83.3% (3.375 g every 8 hrs, 4-hr infusion), 87.1% (4.5 g every 8 hrs, 4-hr infusion), and 89.6% (4.5 g every 6 hrs, 3-hr infusion). For continuous-infusion regimens, the cumulative fractions of response were 82.3% (10.125 g), 86.5% (13.5 g), 89.2% (18 g), 90.0% (20.25 g), and 90.6% (22.5 g). Both prolonged- and continuous-infusion strategies improved the pharmacodynamics of piperacillin-tazobactam over those of traditional 30-minute intermittent-infusion regimens. Prolonged- and continuous infusion regimens that contained the same daily doses of piperacillin had similar likelihoods of bactericidal exposure. Thus, the selection of dosing strategy depends on the availability of intravenous access versus the convenience of once-daily administration.


Ecology: engineered food webs.
An important new study shows that, in a food web, the strengths and arrangement of the interactions between species are determining factors of stability of the system.


Role for mitogen-activated protein kinases in phenobarbital-induced expression of cytochrome P450 2B in primary cultures of rat hepatocytes.
Phenobarbital (PB) alters expression of numerous hepatic genes, including genes of cytochrome P450 2B1 and 2B2 (CYP2B). However, the intracellular mechanisms remain to be fully elucidated. The present study investigated the involvement of mitogen-activated protein kinases (MAPKs) in rat hepatocytes in primary culture. We showed that PB induced an early, dose-dependent activation of ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase) and p38 MAPKs. Regarding the PB (1mM) induction of CYP2B mRNA expression, while chemically inhibiting JNK had no effect, specific inhibitors of the ERK (U0-126) and p38 (SB-203580) pathways up- and down-regulated this expression, respectively. However, although such a regulation was confirmed when testing the effect of a dominant negative mutant of the ERK pathway on the CYP2B2 enhancer-promoter activity, no such transcriptional role was found with the p38 pathway. Moreover, upon arrest of transcription, the stability of CYP2B mRNA remained unaffected by SB-203580. In conclusion, we show that the ERK pathway negatively regulates CYP2B2 enhancer-promoter activity and that, despite p38 activation upon PB exposure, the sensitivity of CYP2B mRNA expression to SB-203580 appears to be unrelated to this kinase.


Surface electrodes are not sufficient to detect neurotonic discharges: observations in a porcine model and clinical review of deltoid electromyographic monitoring using multiple electrodes.
In order to define the preferred electromyographic monitoring method during spine surgery, (1) a porcine model of neurotonic generation after lumbar root compression was developed and (2) intraoperative use of deltoid muscle intramuscular needle, subdermal needle, and surface electrodes was retrospectively reviewed. In pigs, an array of intramuscular needle, subdermal needle, and surface electrode derivations was differentially amplified at identical gain and filter settings. Nerve root compression generated neurotonic discharges whose amplitudes were compared at each derivation. Clinically, 25 deltoid muscles in 13 patients were simultaneously monitored (during cervical spine surgery at the C4-C5 level) with surface, subdermal needle, and intramuscular needle electrode pairs, differentially amplified at identical gain and filter settings. Non-repeating neurotonic discharges were assigned, by amplitude and morphology, to best derivation (intramuscular, subdermal, surface or combination); coincident amplitudes were measured at the maximum deflection among the three derivations. Actual voltage detected between clinical methods was analyzed with Friedman's test and any detection versus none by general estimating equations(GEE) using SAS. The advantage of two needles over one in detection of any voltage was assessed using McNemar's test. Compressed porcine lumbar roots generated neurotonics which were identifiable at intramuscular sites only. Clinically, 31 neurotonics were identified: 20/31 at intramuscular, 5/31 at subdermal, and 6/31 equally well at intramuscular and subdermal derivations. Intramuscular detected neurotonics better than subdermal derivations (z = 2.9, P < .004). No voltage was recorded at the surface in 16/31 neurotonics. For detection of any voltage, intramuscular was better than subdermal (z = -1.5, P = .04) or surface electrodes (z = -2.7, P < .001). Electromyographic moni- toring of spine surgery should not be done by surface electrodes. Because sensitive neurotonic detection requires near field recording, intramuscular electrodes are preferred. Monitoring of a myotome at particularly increased risk may suggest multiple intramuscular electrodes.


Genetic association between the cyclin-dependent kinase inhibitor gene p27/Kip1 polymorphism (rs34330) and cancer susceptibility: a meta-analysis.
The p27 rs34330 (-79C/T) polymorphism has been widely studied for human cancer susceptibility. The current findings, however, still remained controversial. Therefore, we performed the meta-analysis to provide a more accurate result. Eligible studies were identified from PubMed database up to June 2015. The association of p27 rs34330 polymorphism and cancer susceptibility was estimated with odds ratios and corresponding 95% confidence intervals. The meta-analysis was performed with Stata 12. A total of ten studies with 11,214 cases and more than 8,776 controls were included in the meta-analysis (including breast, lung, thyroid, endometrial, and hepatocellular cancer). In pooled analysis, p27 gene rs34330 polymorphism significantly increased the cancer susceptibility. Subgroup analysis indicated that the elevated risk was observed under all the genetic models for Asians and under three genetic models for Caucasians. Results of sensitivity analysis were similar to the overall results. The results suggested that the p27 rs34330 polymorphism increased the cancer susceptibility, especially in Asians. Further well-designed and large sample size studies are warranted to verify the conclusion.


Case report: retroperitoneoscopic pheochromocytoma removal in an adult with Eisenmenger's syndrome.
Patients with uncorrected or palliated, complex congenital heart lesions requiring surgery can benefit from laparoscopic techniques, but retroperitoneal insufflation may render them hemodynamically unstable. Alterations in cardiopulmonary physiology during retroperitoneal insufflation have been studied, yet there are no cases detailing this approach in patients with congenital heart lesions. We present a case of a pheochromocytoma removal via retroperitoneoscopy in a patient with a palliated, complex heart lesion. A 28-yr-old woman was admitted for removal of a pheochromocytoma through retroperitoneoscopy. The main feature of her heart disease was a complete atrioventricular canal defect. She eventually developed Eisenmenger's syndrome and became chronically cyanotic. Retroperitoneal insufflation with CO2 gas did not change hemodynamic variables. Significant increases in peak airway pressures were encountered, possibly due to the distending effects of insufflation, or due to increasing the minute ventilation to reduce exogenous CO2. Arterial CO2 remained stable, but a significant increase between end-tidal and arterial levels became apparent with insufflation. Tumour manipulation led to systemic (and possibly pulmonary) hypertension, which exacerbated ventricular dysfunction. This condition resulted in atrioventricular valve regurgitation, as seen on transesophageal echocardiography, and diminished pulmonary blood flow with subsequent desaturation. These changes resolved with antihypertensive medications. The patient's trachea was extubated four hours postoperatively, and she recovered uneventfully. Patients with altered cardiopulmonary physiology may tolerate retroperitoneoscopic insufflation with relative hemodynamic stability. Appropriate use of short-acting, vasoactive drugs and aggressive monitoring of PaCO2 and hemodynamic variables is required.


Comparing the efficacy of plasma exeresis and cryotherapy for the treatment of seborrheic keratosis: A randomized controlled trial.
Seborrheic keratoses (SK) is a benign epithelial skin tumor and plasma exeresis is a new technique. To compare the efficacy and safety of plasma exeresis and cryotherapy for treating SK. This study is a randomized controlled trial (RCT). One side of each patient was randomly treated with plasma exeresis (peak-to-peak voltage of 3.44 kV and a frequency of 62.5 kHz) and the other side with cryotherapy. Thirty-five males were enrolled. At week 3, 37.1 % (N = 13) of lesions treated by plasma exeresis were clear, which was higher than those treated by cryotherapy 17.1% (N = 6). However, this difference was not significant (p-value: 0.06). At week 6, 16 (57.1 %) out of 28 remaining lesions, treated by plasma exeresis were clear, which was significantly higher (p-value: 0.005) than those completely cleared by cryotherapy in 6 out of 29 remaining lesions (20.7%). The mean physician assessment scale score was significantly reduced in both groups in the second follow-up (plasma group first follow-up 0.91 ± 0.89 vs. second follow-up 0.5 ± 0.64 and p-value: 0.0031; cryo group first follow-up 1.4 ± 0.84 vs. second follow-up 1.1 ± 0.72 and p-value: 0.0002). Regarding side effects, no significant difference was seen (p = 0.438). The most common complications in the plasma and cryotherapy groups were erythema (10/19, 52.63%) and hypo pigmentation (5/13, 38.46%). Both cryotherapy and plasma exeresis are effective. We observed a significantly higher cleared lesions treated with plasma exeresis in 6 weeks and after two sessions.


Hair mercury content among residents of Cumana, Venezuela.
Mercury in scalp hair of 135 individuals (65 males, 70 females) between the ages of 6 and 61 residing in Cumaná, Venezuela, were determined by cold vapour atomic absorption. The average hair mercury content was 2.01 +/- 0.51 ppm, with a range of 0.42-6.08 ppm. The differences in the distribution of Hg in the hair of male and female subjects were insignificant. Hair mercury content was not correlated with age.


Hemispheric functioning in children with subtypes of attention-deficit/hyperactivity disorder.
The authors investigated line bisection performance in children with Attention-Deficit/Hyperactivity Disorder (AD/HD) subtypes. Previous research with neurotypical children found a rightward bias with right-hand use and a leftward bias with left-hand use; however, research with AD/HD participants has failed to similarly measure the effects of hand use, which was the focus of this study. Line bisection was used to measure differences in right hemisphere functioning in children (7 to 12 years) with AD/HD-I and AD/HD-C. Initial AD/HD group findings (without subtype differentiation) replicated previous research. However, further subtype analyses showed that the ADHD-I and ADHD-C groups perform significantly differently. Specifically, the ADHD-I group showed a leftward bias, irrespective of hand use, and the ADHD-C group showed a rightward bias, irrespective of hand use. These findings suggest that the subtypes represent two distinct disorders and that, unlike ADHD-C, ADHD-I may not be the result of right hemisphere dysfunction.


Association of reactive oxygen and nitrogen intermediate and complement levels with apoptosis of peripheral blood mononuclear cells in lupus patients.
Both increased production of reactive oxygen and nitrogen intermediates (RONI) and reduced levels of complement may play a role in the increased apoptosis and reduced clearance of apoptotic cells in systemic lupus erythematosus (SLE). The objective of this study was to evaluate both processes in a parallel, prospective, longitudinal manner. Sixty-seven SLE patients were evaluated during multiple visits, and 31 healthy control subjects were evaluated once or twice. Clinical and laboratory features of SLE disease activity were determined, and blood was collected for measurement of serum nitrate plus nitrite (NOx) levels and for isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were cultured with a nitric oxide (NO) donor and SLE or control plasma, with or without heat inactivation, cobra venom factor (CVF), or lipopolysaccharide plus interferon-gamma treatment. Cells were analyzed for apoptotic index (AI), cellular subsets, and RONI production. The PBMC AI was associated with SLE and was inversely associated with complement levels over time. Changes in the AI with addition of a NO donor was longitudinally associated with serum NOx levels, and stimulation of SLE PBMCs led to parallel increases in RONI production and apoptosis. Addition of SLE plasma resulted in a greater PBMC AI, an effect that was increased with heat inactivation and was corrected with CVF treatment. These data suggest that the greater AI observed in SLE PBMCs relates to increased PBMC RONI production and reduced complement levels. The longitudinal nature of these parallel associations within individuals suggests that these processes are dynamic and additive.


"Two route infusion chemotherapy" using cis-Diamminedichloroplatinum (II) and its antidote, sodium thiosulfate, for metastatic liver tumors in rats.
We studied the effects of combination chemotherapy of an antitumor drug cis-diamminedichloroplatinum (II) (DDP) and its potent antidote, sodium thiosulfate (STS) in rat liver tumor systems. This therapy was given to female WKA rats with metastatic liver tumors 13 days after inoculation of syngeneic hepatoma cells through the mesenteric vein. DDP and STS were administered via two different routes, hepatic artery and femoral vein, respectively (we call this treatment "two route infusion chemotherapy"). The antitumor effects were evaluated 21 days after the treatment by calculating the tumor weight from the total weight of the liver. Tumor weights of rats treated with 20 mg/kg of intra-arterial DDP plus 1,054 mg/kg of systemic STS (group A), 5 mg/kg of intra-arterial DDP alone (group B), and 5 mg/kg of systemic DDP alone (group C) were, about one fifth, two fifths and three fifths of the tumor weights in the untreated controls, respectively. In group A, no rats died despite administration of a 4-fold higher DDP dose than in the latter two groups B and C in which 14-18 per cent of the rats died, due to DDP-induced toxicity. The patterns of body weight gain in the three groups after the chemotherapy were much the same. Our results clearly indicate that the antitumor effect of DDP on metastatic liver tumors in rats can remarkably be enhanced by the "two route infusion chemotherapy" of DDP and STS.


HPV immunisation and cervical screening--confirmation of changed performance of cytology as a screening test in immunised women: a retrospective population-based cohort study.
To document the effect of bivalent HPV immunisation on cervical cytology as a screening test and assess the implications of any change, using a retrospective analysis of routinely collected data from the Scottish Cervical Screening Programme (SCSP). Data were extracted from the Scottish Cervical Call Recall System (SCCRS), the Scottish Population Register and the Scottish Index of Multiple Deprivation. A total of 95 876 cytology records with 2226 linked histology records from women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. The performance of cervical cytology as a screening test was evaluated using the key performance indicators used routinely in the English and Scottish Cervical Screening Programmes (NHSCSP and SCSP), and related to vaccination status. Significant reductions in positive predictive value (16%) and abnormal predictive value (63%) for CIN2+ and the mean colposcopy score (18%) were observed. A significant increase (38%) in the number of women who had to be referred to colposcopy to detect one case of CIN2+ was shown. The negative predictive value of negative- or low-grade cytology for CIN2+ increased significantly (12%). Sensitivity and specificity, as used by the UK cervical screening programmes, were maintained. The lower incidence of disease in vaccinated women alters the key performance indicators of cervical cytology used to monitor the quality of the screening programme. These findings have implications for screening, colposcopy referral criteria, colposcopy practice and histology reporting.


Interactions between iron availability, aluminium toxicity and fungal siderophores.
The influence of iron, aluminium and of the combined application of both metals on microbial biomass and production of siderophores by three fungi (Aspergillus nidulans, Neurospora crassa and Hymenoscyphus ericae) were investigated. All three species showed a strong iron regulation and Al-sensitivity of siderophore biosynthesis although several differences remained species dependent. Inhibitory effects of Fe and Al on siderophore-production were additive and the higher binding capacity of siderophores towards iron could be compensated by a higher Al-availability. Although pH itself is also important for regulation of siderophore biosynthesis, an indirect effect of Al on siderophore production via an Al-induced pH decrease could be outlined. The toxic effects of Al resulting in a reduced biomass production were compensated by high Fe-availability, whereas the addition of DFAM, a bacterial siderophore, enhanced Al-toxicity.


[Observations on the accent-method of Smith in the management of voice and speech disturbances. Part II (author's transl)].
In an earlier paper [HNO 25, 102 (1977)], the accent-method for the treatment of voice disorders has been described in detail. The rhythmical pronunciation of stressed ("accentuated") syllables with a physiologically correct phonatory respiration and a loose articulation form the basis for this method, and allow treatment of voice disorders as well as problems related to abnormal speech behavior. Further discussion is based on present theories of the physics and the physiology of voice function as well as on concepts from modern psychology and pedagogics.