The value of preoperative planning.
"Better to throw your disasters into the waste paper basket than to consign your patients to the scrap heap" has been a proverb of Jeff Mast, one of the greatest fracture and deformity surgeons in the history of our specialty. Stated slightly more scientifically, one of the major values of simulation is that it allows one to make mistakes in a consequence-free environment. Preoperative planning is the focus of this article. The primary goal is not to provide you with a recipe of how to steps. Rather, the primary goal of this article is to explain why preoperative planning should be standard, to clarify what should be included, and to provide examples of what can happen when planning is ignored. At the end of this, we should all feel the need to approach fracture care more intellectually with forethought, both in our own practices and in our educational system.


Thrombosis of the umbilical cord: analysis of 52 cases and literature review.
Fifty-two cases of umbilical cord thrombosis from 3 patients populations are analyzed and compared with 68 cases from the literature. The incidence of cord thrombosis is approximately 1/1300 deliveries, 1/1000 perinatal autopsies, and 1/250 high-risk gestations. There is a slight male predominance. Umbilical vein thrombosis occurs more frequently than thrombosis of one or both umbilical arteries, but poor fetal outcome is more likely with arterial thrombosis. The mechanism of fetal death when only one umbilical artery is thrombosed is illustrated and discussed. The strong association between cord thrombosis and perinatal morbidity and mortality is not noted among prospective cases but, when present, is related to additional umbilical cord abnormalities, obstetrical complications, or systemic fetal conditions that are the likely cause of both the thrombosis and the poor fetal outcome. The pathogenetic relationship between cord thrombosis and these associated conditions is discussed, and it is concluded that cord thrombosis is a marker of both the severity of these conditions and the likelihood of poor fetal outcome.


Social class gradients and serum uric acid in males and females.
The relation between serum uric acid and social class is examined by sex among 910 persons in Wensleydale, Yorkshire, 321 persons in Watford, Hertfordshire, and 1,213 persons in New Haven, Connecticut, all of whom were drawn from the general population. Among the men of Wensleydale there is a tendency of marginal significance at the 5% level for serum uric acid to increase with decreasing social class; in the New Haven women this same trend is significant at the 2.5% level; no trend was found among any of the other four sex-specific groups. Age did not account for the patterns observed. The difference between these findings and those of several studies from the United States is consistent with the view that both serum uric acid levels and gout are under multifactorial control.


Organ donation: attitude and knowledge of nurses in South Africa.
Various factors influence the process of organ donation. As a result, there is a shortage of organs for transplant. Poor communication and cooperation between transplant coordinators and intensive care nursing staff can lead to the non-referral of potential organ donors, which is detrimental to the process. The purpose of this research was to ascertain the attitude and knowledge of the transplant coordinators and intensive care nursing staff that work in intensive care units during organ donation. Contextual descriptive research was carried out by compiling literature-based questionnaires, one each for the transplant coordinators and intensive care nursing staff, and then analysing responses. The indications are that problem areas exist between the role players in the organ transplant process. Guidelines were drawn up for the improvement of communication and cooperation between them in order to promote organ donation.


Telemedical education: teaching spirometry on the Internet.
Advances in portable equipment have led to routine spirometry testing outside of formal pulmonary function laboratories. Practitioners ordering these tests are not formally trained in spirometry interpretation. Providing effective off-site training can be challenging. Our objective was to develop a remotely accessible computer-based tutorial for teaching spirometry interpretation to nonpulmonologists. We designed an educational module that was accessible via the Internet and tested by 65 medical trainees at a major university medical center. In addition, the module was posted within the Virtual Hospital on the World Wide Web. Increases in spirometry interpretative skills were assessed using pre- and post-tests submitted electronically. The spirometry module significantly improved spirometry interpretation by nonspecialist trainees. This improvement included a broad increase in knowledge base and was observed independent of training level and prior spirometry reading experience. We conclude that computer-based tutorials can effectively train off-site practitioners in spirometry interpretation. This technology allows for the dissemination of educational material from a central site of expertise and provides a valuable adjunct to limited teaching resources.


Metallic fragments on the surface of miniplates and screws before insertion.
Particulate metal fragments have been identified histologically within the tissues adjacent to miniplates and screws after they have been removed. These were thought to have been caused by corrosion and degradation of the metal. However, the particles may have originated from rough edges or from protuberances left on the metal surface after cutting and machining during manufacture, and subsequently become detached. This study was undertaken to analyse the incidence and distribution of metal fragments on the surface of miniplates and screws before use. Fifteen miniplates and 60 screws were examined by stereomicroscopy and scanning electron microscopy. Rough metal edges or protuberances were identified on over half the samples, mostly in the countersink area of screw holes on the mini-plates. Fragments were detected within some of the cruciform screw heads and on some screw threads. We conclude that metal protuberances are present on the surface of mini-plate components when they are received from the manufacturer. There is a risk that the fragments might be detached and deposited into the tissues during insertion.


Atomic charges in molecules defined by molecular real space partition into atomic subspaces.
Atomic charge (AC), which is the charge distribution of a molecule, is an important property that is closely associated with structures, reactivities, and intra- and inter-molecular interactions among molecules. Several theoretical models or methods can be used to obtain the magnitudes of AC with different characteristics. These models can be classified into fuzzy-atoms models and models partitioning a molecule into individual atoms with sharp boundaries. The first category includes Mulliken, natural population analysis (NPA), Hirshfeld, Merz-Kollman-Singh (MK), CHELPG, the electronegativity equalization method (EEM), the atom-bond electronegativity equalization method (ABEEM), and atomic polar tensor (APT). The second category is derived from quantum chemical topology (QCT) and includes the quantum theory of atoms in molecules (QTAIM) and QCT analysis based on the potential acting on one electron in a molecule (PAEMQCT). Herein, after giving a bird's-eye view of the population methods of the first category, we specifically describe some features of the second category. We only present the basic framework of QCT for obtaining ACs from QTAIM and PAEMQCT and show their important characteristics. QCT establishes the basis of the following chemical concept: a molecule is spatially partitioned into individual atoms with sharp boundaries. The ACs from QTAIM are close to the atomic valence in chemistry, and ACs from PAEMQCT may be practically suitable for modeling intra- and inter-molecular interactions.


Self-Assembled Pea Protein Isolate Nanoparticles with Various Sizes: Explore the Formation Mechanism.
Pea protein isolate nanoparticles (PPINs) were successfully prepared by potassium metabisulfite (K2S2O5). The disulfide bonds were disrupted by K2S2O5, and then the PPINs were formed through self-assembly. The average diameter of PPINs increased from 124.7 to 297.5 nm as the concentration of K2S2O5 was increased from 2 to 8 mM, and the PPINs showed higher ζ-potentials (-32.2 to -35.8 mV) and unimodal distribution. The content of free sulfhydryl groups first increased and then decreased with the fracture and reformation of disulfide bonds. Subsequently, the increase of the β-sheet, which has considerable hydrophobicity, promoted the formation of PPINs. The formation mechanism of PPINs was explored by dissociation tests: hydrophobic interactions maintained the basic skeleton of PPINs, disulfide bonds stabilized the internal structure, and hydrogen bonds existed on the exterior of the particles. This study provided a simple and economical method to fabricate nanoparticles.


Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy.
Photodynamic therapy (PDT) is a promising treatment strategy for malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is used as a precursor of the photosensitizer, protoporphyrin IX (PpIX), in dermatology and urology. However, the effectiveness of ALA-PDT is limited by the relatively poor bioavailability of ALA and rapid conversion of PpIX to haem. The main goal of this study was to prepare and investigate a library of single conjugates designed to coadminister the bioactive agents ALA and hydroxypyridinone (HPO) iron chelators. A significant increase in intracellular PpIX levels was observed in all cell lines tested when compared to the administration of ALA alone. The higher PpIX levels observed using the conjugates correlated well with the observed phototoxicity following exposure of cells to light. Passive diffusion appears to be the main mechanism for the majority of ALA-HPOs investigated. This study demonstrates that ALA-HPOs significantly enhance phototherapeutic metabolite formation and phototoxicity.


The occurrence of consanguineous marriages in Hungary.
The occurrence of first cousin couples was 2.90/00 in Hungary involving three different population samples (about 2,000, 1,000 and 2,000 women after delivery in the capital, two cities, and a city with agricultural characteristics, respectively).


Overexpression of the coenzyme-F420-dependent N5,N10-methylenetetrahydromethanopterin dehydrogenase gene from the hyperthermophilic Methanopyrus kandleri.
The mtd gene encoding coenzyme-F420-dependent N5,N10-methylenetetrahydromethanopterin dehydrogenase (Mtd) in the hyperthermophilic Methanopyrus kandleri has been cloned, sequenced and functionally overexpressed in Escherichia coli. The overproduced enzyme was purified in a 90% yield to apparent homogeneity by means of only one chromatographic step. Its thermostability properties and most of its catalytic properties were the same as those of the native enzyme purified directly from M. kandleri. Only the dependence of the activity on the concentration of lyotropic salts differed slightly. Northern blot analysis revealed that in M. kandleri the mtd gene is monocistronically transcribed.


Removing lead ions from aqueous solutions by the thiosemicarbazide grafted multi-walled carbon nanotubes.
A novel multi-walled carbon nanotubes (MWCNTs) material functionalized with thiosemicarbazide was synthesized successfully and used to remove lead ions from aqueous solutions. The technologies of Fourier Transform Infrared Spectroscopy, scanning electron microscopy and thermal gravimetric analysis were used to characterize the structure and properties of thiosemicarbazide grafted MWCNTs. The adsorption conditions, such as pH, contact time and temperature, were investigated. The results showed pH affected the adsorption process greatly, and the adsorption process reached equilibrium within 60 min. The maximum adsorption capacity was 42.01 mg/g. The adsorption process fitted well with the pseudo-second-order kinetic model and the Langmuir model. The thermodynamic parameters indicated the adsorption process was endothermic and spontaneous in nature.


Are joint torque models limited by an assumption of monoarticularity?
This study determines whether maximal voluntary ankle plantar flexor torque could be more accurately represented using a torque generator that is a function of both knee and ankle kinematics. Isovelocity and isometric ankle plantar flexor torques were measured on a single participant for knee joint angles of 111° to 169° (approximately full extension) using a Contrex MJ dynamometer. Maximal voluntary torque was represented by a 19-parameter two-joint function of ankle and knee joint angles and angular velocities with the parameters determined by minimizing a weighted root mean square difference between measured torques and the two-joint function. The weighted root mean square difference between the two-joint function and the measured torques was 10 N-m or 3% of maximum torque. The two-joint function was a more accurate representation of maximal voluntary ankle plantar flexor torques than an existing single-joint function where differences of 19% of maximum torque were found. It is concluded that when the knee is flexed by more than 40°, a two-joint representation is necessary.


[Use of RIA (radioimmunoassay) technics in the identification of narcotics in biological fluids].
Radioimmunoassay has been compared with extraction thin-layer chromatography and gas-chromatography for the detection of morphine and barbiturate in urine. Radioimmunoassay has been found to be the most sensitive and rapid method and its use in large scale screening and forensic toxicology is considered.


Full DFT-D description of a nanoporous supramolecular network on a silicon surface.
We present a full density-functional-theory study taking into account the van der Waals interactions of a 2D supramolecular network adsorbed on the Si(111)√3x√3R30°-boron surface denoted SiB. We show that, contrarily to the previous calculations [B. Baris, V. Luzet, E. Duverger, Ph. Sonnet, F. Palmino, and F. Chérioux, Angew. Chem., Int. Ed. 50, 4094 (2011)] molecule-molecule interactions are attractive, thanks to van der Waals corrections which are essential to describe such systems. We confirm the importance of the substrate effect to achieve the molecular network on the boron doped silicon surface without covalent bond. Our simulated STM images, calculated in the framework of the bSKAN code, give better agreement with the experimental STM images than those obtained by the integrated LDOS calculations within the Tersoff-Hamann approximation. The tungsten tip presence is essential to retrieve three paired lobes as observed experimentally. The observed protrusions arise from the phenyl arms located above silicon adatoms.


Genomic and proteomic expression analysis of Leishmania promastigote and amastigote life stages: the Leishmania genome is constitutively expressed.
Leishmania are protozoan parasites that cause a wide spectrum of clinical diseases in humans and are a major public health risk in several countries. Leishmania life cycle consists of an extracellular flagellated promastigote stage within the midgut of a sandfly vector, and a morphological distinct intracellular amastigote stage within macrophages of a mammalian host. This study reports the use of DNA oligonucleotide genome microarrays representing 8160 genes to analyze the mRNA expression profiles of L. major promastigotes and lesion derived amastigotes. Over 94% of the genes were expressed in both life stages. Advanced statistical analysis identified a surprisingly low degree of differential mRNA expression: 1.4% of the total genes in amastigotes and 1.5% in promastigotes. These microarray results demonstrate that the L. major genome is essentially constitutively expressed in both life stages and suggest that Leishmania is constitutively adapted for survival and replication in either the sandfly vector or macrophage host utilizing an appropriate set of genes for each vastly different environment. Quantitative proteomics, using the isotope coded affinity tag (ICAT) technology and mass spectrometry, was used to identify L. infantum promastigote and axenic amastigote differentially expressed proteins. Of the 91 distinct proteins identified, 8% were differentially expressed in the amastigote stage, 20% were differentially expressed in the promastigote stage, and the remaining 72% were considered constitutively expressed. The differential expression was validated by the identification of previously reported stage specific proteins and identified several amastigote and promastigote novel stage specific proteins.


Effect dietary corn starch intake on pancreatic amylase and intestinal maltase and pH in cattle.
The pH optimum of pancreatic alpha-amylase from grain-fed steers was determined to be 6.9, while that of intestinal maltase was established at 5.8. Both assays were found to be linear up to 1 hr of incubation. The V max of pancreatic amylase was determined to be pancreatic amylase was determined to be 1.15 mg of maltose monohydrate produced/hr. Activities of pancreatic and intestinal maltase were not reduced (P greater than .05) during the interval from sample collection from the animal until analysis 4 hr later when tissues were kept on ice. Twenty-four yearling Holstein steers fed either alfalfa hay at a maintenance level of metabolizable energy (ME) intake or corn at one, two or three times the maintenance ME intake level were slaughtered after being fed 106 days. The pancreas was removed alone with sections of the intestine. Specific activity of pancreatic amylase for steers fed the high level of corn was 129% of that for steers fed the alfalfa diet (P greater than .05). Intestinal maltase activity was highest in the jejunum and decreased toward the ileum. Increasing dietary starch intake resulted in no response (P greater than .05) in maltase activity at 10, 30, 50, 70, or 90% of the small intestine length. The effect of dietary starch level on dieesta pH was dependent on sampling location within the small intestine. There were no dietary effects (P greater than .05) on digesta pH for the first 10% segment of intestine distal to the pylorus. However, in all subsequent sections, digesta pH was higher steers fed the alfalfa diet than for those fed the two higher levels of grain. A calculation for estimating th amount of pancreatic amylase needed to hydrolyze starch presented to small intestine is discussed.


The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community: a report from the HCA database.
Diabetics remain a high-risk group for those undergoing percutaneous coronary intervention (PCI) using balloon angioplasty and/or intracoronary stents for myocardial revascularization. The objective of this study is to compare clinical characteristics, demographics, procedure indications, lesion characteristics, and acute and long-term outcomes between diabetic patients and non-diabetic patients in a community based PCI registry. Information on patient demographics, coronary risk factors, lesion characteristics, procedures, and outcomes were derived from an HCA, Inc. database on all patients undergoing a PCI procedure in one of four community cardiac catheterization laboratories (CCL). A total of 3,139 patients who underwent PCI procedures from July 1, 1999 through September 30, 2000 were enrolled in this study. Approximately one-third of these patients completed a follow-up survey one year after their initial encounter. Analysis was limited to those patients undergoing PCI of native vessels with stents or conventional balloon angioplasty; patients with target lesions in bypass grafts or those treated with atherectomy were excluded. Approximately 23.5% of the patients enrolled in the study were diabetic. This study found no significant difference in any acute outcome between diabetic and non-diabetic patients in the hospital episode associated with the index PCI procedure. However, data from the 1-year follow-up survey indicates diabetic patients tended to have more target lesion revascularization (TLR) (13.6% versus 8.9%; p = 0.07) and more target vessel revascularization (TVR) (17.6% versus 12.7%; p = 0.058) than non-diabetic patients. In addition, adjusted odds ratios indicate that diabetic patients were 1.6 times more likely to have a second PCI procedure in another vessel (p = 0.013), 2.4 times more likely to undergo bypass surgery (p = 0.003), 1.9 times more likely to undergo an additional revascularization procedure (p < 0.001) and 1.8 times more likely to experience any major adverse cardiac events (p < 0.001) than non-diabetic patients during the follow-up period. This study indicates that selected diabetic patients can be treated for myocardial revascularization using PCI procedures with acceptable acute outcomes. However, diabetic patients undergoing PCIs have significantly more disease progression and are more likely to experience the need for recurrent revascularization.


The Potentiality of Herbal Remedies in Primary Sclerosing Cholangitis: From In Vitro to Clinical Studies.
Primary sclerosing cholangitis is a complex pathological condition, characterized by chronic inflammation and fibrosis of the biliary epithelium. Without proper clinical management, progressive bile ducts and liver damage lead to cirrhosis and, ultimately, to liver failure. The known limited role of current drugs for treating this cholangiopathy has driven researchers to assess alternative therapeutic options. Some herbal remedies and their phytochemicals have shown anti-fibrotic properties in different experimental models of hepatic diseases and, occasionally, in clinical trials in primary sclerosing cholangitis patients; however their mechanism of action is not completely understood. This review briefly examines relevant studies focusing on the potential anti-fibrotic properties of Silybum marianum, Curcuma longa, Salvia miltiorrhiza, and quercetin. Each natural product is individually reviewed and the possible mechanisms of action discussed.


fMLP induces Hsp27 expression, attenuates NF-kappaB activation, and confers intestinal epithelial cell protection.
Sustained expression of cytoprotective intestinal epithelial heat shock proteins (Hsps), particularly Hsp27, depends on stimuli derived from bacterial flora. In this study, we examined the role of the bacterial chemotactic peptide fMLP in stimulating colonic epithelial Hsp expression at concentrations encountered in a physiological milieu. Treatment of the polarized human intestinal epithelial cell line Caco2bbe with physiological concentrations of fMLP (10-100 nM) induced expression of Hsp27, but not Hsp72, in a time- and concentration-dependent manner. Induction of Hsp27 by fMLP was specific since the fMLP analogs MRP and MLP were not effective. Hsp27 induction by fMLP was blocked by the fMLP-receptor antagonist BOC-FLFLF and was blocked when the dipeptide transporter PepT1, an entry pathway for fMLP, was silenced. fMLP activated both the p38 and ERK1/2 MAP kinase pathways in Caco2bbe cells, but not the SAPK/JNK pathway. The p38 inhibitor SB203580, but not the MEK-1 inhibitor PD98059, blocked Hsp27 induction by fMLP. fMLP treatment inhibited actin depolymerization and decreased transepithelial resistance caused by the oxidant monochloramine, and this inhibition was reversed by silencing Hsp27 expression. fMLP pretreatment also inhibited activation of proinflammatory transcription factor NF-kappaB by TNF-alpha in Caco2bbe cells, reducing induction of NF-kappaB target genes by TNF-alpha both in human intestinal biopsies and Caco2bbe cells. In conclusion, fMLP may contribute to the maintenance of intestinal homeostasis by mediating physiological expression of Hsp27, enhancing cellular protection, and negatively regulating the inflammatory response.


Stress immunity in lymphomas: mesenchymal cells as a target of therapy.
The role of lymphocytes in eliminating lymphoma cells is based on the interaction between activating receptors on lymphocytes and target surface ligands on lymphoma cells. Stress-related immunity can be triggered both in Hodgkin's (HL) and non-Hodgkin lymphomas (NHL), through the activation of the NKG2D receptor on CD8+ T and gammadelta T lymphocytes, by NKG2D-ligands (NKG2D-L), as the MHC class-I related molecules MIC-A/B and the UL16-binding proteins 1-4 (ULBPs), expressed on lymphoma cells. Furthermore, NKG2D-L can be shed and interact with NKG2D on effector lymphocytes affecting the recognition of lymphoma cells. Proteolytic cleavage of MIC-A is known to depend on the thiol isomerase ERp5 and the disintegrins and metalloproteinases ADAM10 and ADAM17, which also cleave ULPBs. Mesenchymal stromal cells (MSC) are relevant in regulating effector T lymphocytes-mediated lymphoma surveillance. Indeed, MSC can be seen as targets of potential new therapeutic schemes acting on lymphoma microenvironment, to redirect the stress immune response and avoid escape strategies, by inducing stress molecules, inhibiting sheddase activity, shifting cytokine production to Th1 pattern and blocking Treg differentiation.


Association of a new Wolbachia strain with, and its effects on, Leptopilina victoriae, a virulent wasp parasitic to Drosophila spp.
Wolbachia bacteria are ubiquitous intracellular bacteria of arthropods. Often considered reproductive parasites, they can benefit certain host species. We describe a new Wolbachia strain from Leptopilina victoriae, a Drosophila wasp. The strain is closely related to Wolbachia from Culex sp. Located to the posterior poles of oocytes, it manipulates its host's reproduction by inducing a male development type of cytoplasmic incompatibility. We also report its diverse effects on the wasp's life history traits.


Anti-metastatic activity of fangchinoline in human gastric cancer AGS cells.
Fangchinoline (FCL) is an active component isolated from the traditional medicinal plant Stephania tetrandra S. Moore, and has been reported to possess anti-cancer functions in several types of cancers; however, the effect of FCL on gastric cancer metastasis and its underlying molecular mechanisms remain unknown. The current study aimed to investigate the effect of FCL on the cell migration and invasion of human metastatic gastric cancer AGS cells and its mechanisms. Our study demonstrates that FCL dosage dependently suppressed the adhesion, migration and invasion capacities of human gastric cancer AGS cells without obvious cytotoxic effects. Reverse transcription-polymerase chain reaction and western blot assays demonstrated that FCL greatly inhibited the expression of matrix metalloproteinase (MMP)-2 and MMP-9 at both the mRNA and protein levels, while it significantly increased the expression of tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP2 messenger RNAs. Our results also indicated that FCL repressed the phosphorylation of AKT in gastric cancer AGS cells. In summary, FCL may exert its anti-metastatic property in human gastric cancer cells in vitro by suppression of MMP-2 and MMP-9, increase of TIMP1 and TIMP2 genes, and inhibition of AKT phosphorylation. FCL may be a drug candidate for the treatment of gastric cancer metastasis.


Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms.
The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs) showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34(+) cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV) and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF) patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET) and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34(+) cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs.


Size-dependent spin structures in iron nanoparticles.
Using photoemission electron microscopy, we study the magnetization orientation in single 5-25 nm iron particles coupled to a ferromagnetic cobalt support. We find a noncollinear alignment between the particle and substrate magnetization above a particle size of approximately 6 nm and a parallel alignment for smaller sizes. Numerical calculations reveal a transition from an exchange-dominated to an anisotropy-dominated regime on increasing the particle height: the smaller particles are in a single-domain collinear state while larger particles exhibit a spin-spiral magnetic structure determined by the magnetic anisotropy energy.


Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997-2003.
To describe trends in utilization and prescribing of statins and other lipid lowering drugs across Europe from data in routine administrative databases. Observational study in EU member states and Norway. Comparison of annual utilization data for lipid lowering agents by class and drug from national administrative databases for reimbursement over the period 1997-2003, measured in DDDs per 1000 inhabitants/day. Prescribed daily doses (PDD) of statins obtained from a commercial database (IMS Health) for 2000 and 2003, and used to calculate numbers of "patient treatment days" (PTD) in each country in each year. Analysis of PTD to explain increased utilization of statins. Use of lipid lowering agents varied among countries (in 2003, highest in Ireland and Norway, and lowest in Italy), but increased in all countries studied (between 2000 and 2003 by 274% in Ireland and by 56% in France). This increase was entirely due to increases in statin use. Prescribed daily doses of statins increased in all countries for which data was available between 2000 and 2003, but still usually fell below the doses used in the major trials of statins. As a result, the numbers of PTDs increased to a lesser extent than suggested by utilization (e.g. by 192% in Ireland and by 35% in France). One-third of the total rise in utilization was explained by increased PDD, and two-thirds by an increase in numbers of PTDs. Statins dominated the markets in all countries, although fibrates remained strong in France and Belgium (approximately 25% of all lipid lowering agents) and to a lesser extent Germany (10%). Use of statins across Europe has increased hugely over the study period. Some of the increase in use is due to higher prescribed daily doses, but two-thirds is due to increases in numbers of patient days of treatment, either due to more patients treated or less likely to better compliance.


Improving Accuracy in Documenting Cardiopulmonary Arrest Events.
Traditional paper documentation of cardiopulmonary arrest (CPA) events is often inaccurate and incomplete. Electronic documentation supports appropriate process improvements and optimal patient care and contributes to greater accuracy in national databases from which national benchmarks are derived. The aim of this quality improvement initiative was to compare the timeliness and accuracy of paper-based versus electronic documentation of live CPA events. Nurses on four medical-surgical pilot units received training on the use of a handheld electronic device with a documentation app (Full Code Pro) to document live CPA events. The data were downloaded into an Excel file and compared for completeness and accuracy with the data downloaded from the LIFEPAK 15 defibrillator using CODE-STAT 10.0 software. Electronic documentation and traditional paper documentation of events from units where the intervention wasn't implemented (control units) were also compared with the CODE-STAT data. There were 26 CPA events: six on the pilot units were documented using the electronic app, 12 on the pilot units were documented using the paper-based method (the latter were excluded from analysis), and eight on the control units were documented using the existing paper forms. Data accuracy was significantly greater in the electronic group compared with the paper-based group for recorded rhythm (100% versus 13%, P = 0.01) and end-tidal carbon dioxide (67% versus 0%, P = 0.02). The electronic method significantly outperformed the paper-based method in legibility (100% versus 13%, P < 0.01). Staff reported increased satisfaction with the electronic documentation method. Using electronic handheld devices to document live resuscitation events demonstrated the inaccuracies of paper-based documentation, supporting the findings of previous studies. Electronic documentation was superior to paper in overall documentation quality and allowed providers to identify and quickly document the initial rhythm of the event. A larger study using electronic documentation to capture more ventricular fibrillation and ventricular tachycardia arrests would show a greater accuracy of timing, which would have large positive effects on overall resuscitation quality.


Graft-host tolerance in bone marrow transplant chimeras. Absence of graft-versus-host disease is associated with unresponsiveness to minor histocompatibility antigens expressed by all tissues.
Because bone marrow (BM) transplantation is used with increasing frequency, it is important to elucidate the mechanisms involved in the establishment of tolerance to host minor histocompatibility antigens (MiHA) in recipients transplanted with T-cell-undepleted marrow grafts. We have previously shown that BM chimeras transplanted across MiHA barriers showed specific unresponsiveness to MiHA expressed on recipient-type concanavalin A blasts. Because expression of many MiHA is tissue-specific, we wanted to determine if chimera T lymphocytes would be tolerant to MiHA expressed by all host tissues and organs. To investigate this issue, we measured in vivo proliferation of lymphoid cells from normal C57BL/10 (B10) mice and (B10-->LP) chimeras in tissues and organs of lethally irradiated syngeneic and allogeneic recipients. Donor B10 cells were either untreated, or depleted with anti-Thy-1.2, anti-CD4, or anti-CD8 antibodies. Transplantation of B10 cells in LP recipients triggered an important T-cell-dependent 125I-dUrd uptake in several organs that involved both CD4+ and CD8+ cells. Using Thy-1-congeneic mice we showed that in long-term chimeras practically all CD4+ and CD8+ T lymphocytes were derived from hematopoietic progenitors and not from mature T cells present in the BM graft. When (B10-->LP) BM chimera cells were injected to secondary recipients, no proliferation was observed in any organ of LP hosts whereas normal proliferation was seen in H-2k allogeneic hosts. Thus, in these BM chimeras, tolerance encompasses MiHA expressed by all organs.


Permeability modes in fluctuating lipid membranes with DNA-translocating pores.
Membrane pores can significantly alter not only the permeation dynamics of biological membranes but also their elasticity. Large membrane pores able to transport macromolecular contents represent an interesting model to test theoretical predictions that assign active-like (non-equilibrium) behavior to the permeability contributions to the enhanced membrane fluctuations existing in permeable membranes [Maneville et al. Phys. Rev. Lett. 82, 4356 (1999)]. Such high-amplitude active contributions arise from the forced transport of solvent and solutes through the open pores, which becomes even dominant at large permeability. In this paper, we present a detailed experimental analysis of the active shape fluctuations that appear in highly permeable lipid vesicles with large macromolecular pores inserted in the lipid membrane, which are a consequence of transport permeability events occurred in an osmotic gradient. The experimental results are found in quantitative agreement with theory, showing a remarkable dependence with the density of membrane pores and giving account of mechanical compliances and permeability rates that are compatible with the large size of the membrane pore considered. The presence of individual permeation events has been detected in the fluctuation time-series, from which a stochastic distribution of the permeation events compatible with a shot-noise has been deduced. The non-equilibrium character of the membrane fluctuations in a permeation field, even if the membrane pores are mere passive transporters, is clearly demonstrated. Finally, a bio-nano-technology outlook of the proposed synthetic concept is given on the context of prospective uses as active membrane DNA-pores exploitable in gen-delivery applications based on lipid vesicles.


Conservation of the α4β7 lymphocyte homing receptor in HIV-infected patients with distinct transmission routes and disease progression profiles.
The α4β7 is a lymphocyte homing receptor to the gut-associated lymphoid tissue (GALT). HIV-1 gp120 binds to α4β7 integrin through a mimetic tripeptide in V2 and ensures successful infection of GALT. In the present report, we investigated the presence of polymorphisms in the α4β7 cytoplasmic and α4 N-terminal binding domains and their potential association with susceptibility to HIV infection or disease progression. Subjects displaying distinct categories of disease progression or transmission routes (HIV-positive adults, vertically infected infants, and seronegative subjects) had their ITGA4 and ITGB7 gene segments corresponding to virus binding sites and C-terminal domains PCR amplified and sequenced. An absolute conservation of the studied regions was observed in all patients and controls. Albeit polymorphisms in α4β7 may exist in other regions not tracked in this study, α4β7 activation and binding domains do not seem to be polymorphic and are not correlated with distinct patterns of HIV transmission or disease progression.


Comparison of ultrasonic scalpel versus argon-beam and conventional electrocautery for internal thoracic artery dissection.
We used an ultrasonic scalpel (USS) and an argon beam coagulator (ABC) to test their effectiveness and feasibility in comparison to conventional electrocautery for Internal Thoracic Artery (ITA) takedown, time for takedown, number of clips, thermal impact, along with morphological integrity assessed by histology. Ninety-three patients undergoing elective coronary bypass surgery were prospectively randomized into three groups. In thirty-one patients, either an ultrasonic scalpel (USS, group A), an argon-beam coagulator (ABC, group B) or conventional electrocautery (CEC, group C) was used for ITA harvesting. Harvest times for ITA takedown using CEC (16.7 +/- 6 min) was significantly faster compared to ABC (21.6 +/- 8.1 min; p = 0.02) and USS (24.1 +/- 8.1 min; p < 0.001). There was no significant difference comparing harvest times of USS and ABC (p = 0.1). The number of hemostatic clips used was significantly lower when using USS (5.5 +/- 4.6 clips) compared to both CEC (16.6 +/- 6.2 clips; p < 0.001) and ABC (20.4 +/- 6.5 clips; p < 0.001) and significantly lower using CEC compared to ABC (p < 0.007). There were no significant differences in bleeding points within the tissue bed among the groups (ABC 11/31 patients, CEC 11/31 patients and USS 12/31 patients). This study demonstrates that dissection of the ITA pedicle can be safely done with USS, ABC, and CEC. However, USS is associated with less hemostatic clip demand but prolonged harvest time compared it to ABC and CEC; histological assessment revealed no significant difference when comparing groups and equipment used. A variety in design of the hooks may probably ease ultracision practicability.


Amelioration of exosome and mesenchymal stem cells in rats infected with diabetic nephropathy by attenuating early markers and aquaporin-1 expression.
Diabetic nephropathy (DN) is a prevalent diabetic microvascular condition. It is the leading cause of kidney disease in the advanced stages. There is no currently effective treatment available. This research aimed to investigate the curative potentials of exosomes isolated from mesenchymal stem cells affecting DN. This study was performed on 70 male adult albino rats. Adult rats were randomized into seven groups: Group I: Negative control group, Group II: DN group, Group III: Balanites treated group, Group IV: MSCs treated group, Group V: Exosome treated group, Group VI: Balanites + MSCs treated group and Group VII: Balanites + exosome treated group. Following the trial period, blood and renal tissues were subjected to biochemical, gene expression analyses, and histopathological examinations. Results showed that MDA was substantially increased, whereas TAC was significantly decreased in the kidney in the DN group compared to normal health rats. Undesired elevated values of MDA levels and a decrease in TAC were substantially ameliorated in groups co-administered Balanites aegyptiacae with MSCs or exosomes compared to the DN group. A substantial elevation in TNF-α and substantially diminished concentration of IGF-1 were noticed in DN rats compared to normal health rats. Compared to the DN group, the co-administration of Balanites aegyptiacae with MSCs or exosomes substantially improved the undesirable elevated values of TNF-α and IGF-1. Furthermore, in the DN group, the mRNA expression of Vanin-1, Nephrin, and collagen IV was significantly higher than in normal healthy rats. Compared with DN rats, Vanin-1, Nephrin, and collagen IV Upregulation were substantially reduced in groups co-administered Balanites aegyptiacae with MSCs or exosomes. In DN rats, AQP1 expression was significantly lower than in normal healthy rats. Furthermore, the groups co-administered Balanites aegyptiacae with MSCs or exosomes demonstrated a substantial increase in AQP1 mRNA expression compared to DN rats.


[Carrot soup analysis (author's transl)].
The sodium and potassium concentration, the osmolality and the carbohydrate content were determined in carrot soups prepared in 4 different children's hospitals and used as oral therapy for infantile diarrhoea. The results were compared with the sugar/electrolyte solutions increasingly recommended for oral rehydration. If adequately prepared (Moro),the carrot soup can replace enteral loss of sodium and potassium and contains sufficient glucose and sucrose as free sugars to ensure optimum sodium and water absorption in the jejunum. The addition of high osmolar glucose in a commercially available carrot food (Hipp) used in the preparation of the soup in two hospitals increases its osmolality, which might provide an extra strain on the affected intestine of these ill infants.


Proteome analysis of camptothecin-treated cortical neurons using isotope-coded affinity tags.
Isotope-coded affinity tags (ICATs) were employed to identify and quantitate changes in protein expression between control and camptothecin-treated mouse cortical neurons. Proteins extracted from control cortical neurons and those treated with camptothecin were labeled with the light and heavy isotopic versions of the ICAT reagents, respectively. ICAT-labeled samples were combined, proteolytically digested, and the derivatized peptides isolated using immobilized avidin chromatography. The peptides thus isolated were analyzed by reversed-phase liquid chromatography coupled directly to either a conventional ion-trap mass spectrometer (IT-MS) or a Fourier transform ion cyclotron resonance mass spectrometer (FTICR). While a majority of the peptide identifications were accomplished using IT-MS, FTICR was used to quantitate the relative abundances of the ICAT-labeled peptides taking advantage of its high resolution, sensitivity, and duty cycle. By using this combination of MS technologies we have thus far identified and quantified the expression of greater than 125 proteins from control and camptothecin-treated mouse cortical neurons. While proteins from most functional classes of proteins were identified, a particularly large percentage of the enzymes involved in glycolysis and the tricarboxylic acid cycle were observed.


Long-term human B cell lines dependent on interleukin-4 and antibody to CD40.
CD40 is a 45- to 50-kilodalton transmembrane glycoprotein expressed on B lymphocytes, epithelial cells, and some carcinoma cell lines. Human resting B lymphocytes entered a state of sustained proliferation when incubated with both the mouse fibroblastic Ltk- cell line that had been transfected with the human Fc receptor (Fc gamma RII/CDw32) and monoclonal antibodies to CD40. In combination with interleukin-4, factor-dependent long-term normal human B cell lines were generated that were consistently negative for Epstein-Barr viral infection. Thus, cross-linking of CD40 is likely to represent an important phenomenon in the clonal expansion of B cells.


[Peculiarities of theophylline therapy in childhood].
Profound knowledge of the pharmacokinetics of theophylline is a prerequisite to successful therapy. In children the clearance of theophylline is considerably greater than in adults. The required higher dosage in relation to body weight results in more pronounced oscillations of drug levels in serum. Investigations in 280 children in the age of 1 to 18 years with bronchial asthma, treated with theophylline compounds, confirm the necessity of individual dosage and surveillance of the drug level in serum. Instead of the determination of the drug level in serum, its measurement in saliva is sufficiently reliable and less molesting. Checks of drug level are also a valuable educational measure to improve patients' compliance with drug intake. The effectivity of asthma therapy in children could be decisively improved by an adequate formulation of a slow release preparation of theophylline.


Dexamethasone and sphingolipids inhibit concanavalin A stimulated glucose uptake in 3T3-L1 fibroblasts.
Studies were carried out in 3T3-L1 fibroblasts to determine the effect of sphingolipids and corticosteroids on concanavalin A stimulated glucose uptake. Sphinganine (40 microM) and sphingosine (40 AND 100 microM) significantly inhibited concanavalin A stimulated glucose uptake (P less than 0.025 & less than 0.005). Prior incubation with 10(-7) M dexamethasone also significantly inhibited concanavalin A stimulated glucose uptake (P less than 0.005). The known effects of corticosteroids on sphingolipid synthesis, degradation, and tissue levels, suggest inhibition by corticosteroids of glucose uptake may be through effects of the steroid on sphingolipid metabolism.


Metformin-clomiphene citrate vs. clomiphene citrate alone: Polycystic ovarian syndrome.
Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women that is associated with reproductive and metabolic disorders. We compared the ovulation and conception rates after the treatment with clomiphene citrate (CC) alone and in combination with metformin in infertile patients presented with polycystic ovarian syndrome (PCOS). This randomized controlled trial of independent cases and controls was conducted at the Department of Obstetrics and Gynecology, Hera General Hospital, Makkah, Saudi Arabia from February 01 to December 31, 2008. The 42 subjects diagnosed as PCOS were divided into group A and B (21 subjects in each) for management with CC + metformin and CC alone, respectively. Group A received 500 mg three times a day of metformin continuously from the first cycle for 6 months or till pregnancy was confirmed. In both groups CC was started at a dose of 50 mg from day-2 till day-6 of the menstrual cycle. The dose of CC was increased to 100 mg in second and 150 mg in third cycle, and then remained 150 mg for the remaining three cycles. With ovulation the dose of CC was unaltered in both groups. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 16. More than 50% females in both groups were had body mass index > 25. Group A achieved high rate of regular cycles, ovulation success, and conception than group B (71.4% vs. 38.1%; P = 0.03), (76.2% vs. 38.1%; P = 0.021), and (66.6% vs. 28.6%; P = 0.01), respectively. Management with metformin + CC increased the ovulation and conception rates.


Role of salivary miRNAs in the diagnosis of gastrointestinal disorders: a mini-review of available evidence.
MiRNAs are short, non-coding RNA molecules, which are involved in the regulation of gene expression and which play an important role in various biological processes, including inflammation and cell cycle regulation. The possibility of detecting their extracellular expression, within body fluids, represented the main background for their potential use as non-invasive biomarkers of various diseases. Salivary miRNAs particularly gained interest recently due to the facile collection of stimulated/unstimulated saliva and their stability among healthy subjects. Furthermore, miRNAs seem to represent biomarker candidates of gastrointestinal disorders, with miRNA-based therapeutics showing great potential in those conditions. This review aimed to highlight available evidence on the role of salivary miRNAs in different gastrointestinal conditions. Most salivary-based miRNA studies available in the literature that focused on pathologies of the gastrointestinal tract have so far been conducted on pancreatic cancer patients and delivered reliable results. A few studies also showed the diagnostic utility of salivary miRNAs in conditions such as esophagitis, esophageal cancer, colorectal cancer, or inflammatory bowel disease. Moreover, several authors showed that salivary miRNAs may confidently be used as biomarkers of gastric cancer, but the use of salivary miRNA candidates in gastric inflammation and pre-malignant lesions, essential stages of Correa's cascade, is still put into question. On the other hand, besides miRNAs, other salivary omics have shown biomarker potential in gastro-intestinal conditions. The limited available data suggest that salivary miRNAs may represent reliable biomarker candidates for gastrointestinal conditions. However, their diagnostic potential requires validation through future research, performed on larger cohorts.


A stochastic differential equation for exposure yields a beta distribution.
This paper presents a stochastic differential equation for exposure based on a modified version of the standard dilution ventilation equation. An equilibrium solution is obtained with the assumption that variability in the rate of change of concentration is proportional to the product of concentration and one minus concentration. Appropriate definitions for concentration are used to ensure a physically consistent model. The probability distribution for exposure that results is the standard beta distribution. This model is supported by several exposure data sets, which fit the beta distribution well. Issues regarding parameter estimation for the beta distribution, and application of the model are presented. Recommendations are made for simultaneously collecting contaminant generation rate information, ventilation rates, and time-dependent breathing-zone tracer concentrations, in addition to the exposure data.


Astrocyte-Microglia Crosstalk: A Novel Target for the Treatment of Migraine.
Migraine is a pervasive neurologic disease closely related to neurogenic inflammation. The astrocytes and microglia in the central nervous system are vital in inducing neurogenic inflammation in migraine. Recently, it has been found that there may be a crosstalk phenomenon between microglia and astrocytes, which plays a crucial part in the pathology and treatment of Alzheimer's disease and other central nervous system diseases closely related to inflammation, thus becoming a novel hotspot in neuroimmune research. However, the role of the crosstalk between microglia and astrocytes in the pathogenesis and treatment of migraine is yet to be discussed. Based on the preliminary literature reports, we have reviewed relevant evidence of the crosstalk between microglia and astrocytes in the pathogenesis of migraine and summarized the crosstalk pathways, thereby hoping to provide novel ideas for future research and treatment.


Thoracoscopic esophagectomy for esophageal carcinoma after peroral endoscopic myotomy for esophageal achalasia: a case report.
Esophageal achalasia causes dysphagia following impaired relaxation of the lower esophageal sphincter due to the degeneration of Auerbach's plexus in the esophageal smooth muscle. Recently, peroral endoscopic myotomy (POEM) has become one of the preferred treatment options for esophageal achalasia. However, pathomorphological changes after POEM have not been well examined. A 65-year-old man with a history of POEM for esophageal achalasia was diagnosed with clinical stage II (cT2-N0-M0) thoracic esophageal squamous cell carcinoma and was consequently treated with neoadjuvant chemotherapy followed by thoracoscopic esophagectomy. Intraoperatively, the esophagus appeared dilated, reflecting esophageal achalasia; however, fairly slight fibrous adhesions were observed between the esophagus and the pericardial surface despite previously performed POEM via an anterior incision. Histopathological examination revealed esophageal wall thickening, edema, and fibrosis extending from the lamina propria to the submucosa. Besides, the majority of the inner layer and some proportion of the outer layer of the muscularis propria were found to be missing or atrophic at the esophagogastric junction (EGJ). No ganglion cells could be detected at the Auerbach's plexus. The previous history of POEM did not affect circumferential mediastinal periesophageal dissection during thoracoscopic esophagectomy. Nevertheless, a large proportion of the inner layer of the muscularis propria at the EGJ level seemed to have become lost or atrophic because of the POEM procedure.


From anilines to isatins: oxidative palladium-catalyzed double carbonylation of C-H bonds.
A novel palladium-catalyzed C-H double carbonylation introduces two adjacent carbonyl groups for the synthesis of isatins from readily available anilines. The reaction proceeds under atmospheric pressure of CO with high regioselectivity and without any additives. Density functional theory investigations indicate that the palladium-catalyzed double carbonylation catalytic cycle is plausible.


Mode scanning: heating pattern synthesis with ultrasound phased arrays.
Modes, the characteristic symmetric focal patterns of an ultrasound phased array, prove especially useful for hyperthermia. Modes cancel the complex pressure fields exactly along the central axis, eliminating axial constructive interference both proximal and distal to the treatment volume. A simple calculation exploits planar or rotational array symmetry and produces the driving signals which generate modal focal patterns. Results show that temporal mode scanning improves heating patterns considerably, expanding the maximum treatable size of the tumour volume.


Manipulation of KLF4 expression generates iPSCs paused at successive stages of reprogramming.
The detailed mechanism of reprogramming somatic cells into induced pluripotent stem cells (iPSCs) remains largely unknown. Partially reprogrammed iPSCs are informative and useful for understanding the mechanism of reprogramming but remain technically difficult to generate in a predictable and reproducible manner. Using replication-defective and persistent Sendai virus (SeVdp) vectors, we analyzed the effect of decreasing the expression levels of OCT4, SOX2, KLF4, and c-MYC and found that low KLF4 expression reproducibly gives rise to a homogeneous population of partially reprogrammed iPSCs. Upregulation of KLF4 allows these cells to resume reprogramming, indicating that they are paused iPSCs that remain on the path toward pluripotency. Paused iPSCs with different KLF4 expression levels remain at distinct intermediate stages of reprogramming. This SeVdp-based stage-specific reprogramming system (3S reprogramming system) is applicable for both mouse and human somatic cells and will facilitate the mechanistic analysis of reprogramming.


Nested Graft for Acral Lichen Sclerosus of the Feet: A Surgical Treatment for an Inflammatory Disease.
The "nested graft" is an innovative and well-defined surgical technique used for chronic wound healing that induces the de-senescence of fibroblasts in the wound bed. We report a case of a 76-year-old man affected by plantar chronic wounds because of acral lichen sclerosus and atrophicus localized at both feet and treated for many years successfully with immunosuppressive agents. For cardiological dysfunction, systemic therapy was reduced to low dosage of steroids with an increase of ulcerations (5 × 2 cm). So we decided to perform the nested graft on the plantar region. After the surgical procedure, all the grafted ulcers healed, and at a 4-month follow-up, no signs of lichen sclerosus were present.


Research on Optimization of Pooling System and Its Application in Drug Supply Chain Based on Big Data Analysis.
Reform of drug procurement is being extensively implemented and expanded in China, especially in today's big data environment. However, the pattern of supply mode innovation lags behind procurement improvement. Problems in financial strain and supply break frequently occur, which affect the stability of drug supply. Drug Pooling System is proposed and applied in a few pilot cities to resolve these problems. From the perspective of supply chain, this study analyzes the process of setting important parameters and sets out the tasks of involved parties in a pooling system according to the issues identified in the pilot run. The approach is based on big data analysis and simulation using system dynamic theory and modeling of Vensim software to optimize system performance. This study proposes a theoretical framework to resolve problems and attempts to provide a valuable reference for future application of pooling systems.


Computer-directed stereotactic biopsy of intrinsic brain stem lesions.
Despite advances in the neuro-imaging of the brain stem, an accurate diagnosis of intrinsic lesions in this region requires tissue sampling and histological verification. We have performed a series of computer-directed stereotactic procedures in 12 patients with intrinsic brain stem lesions. A positive diagnosis was obtained in 11 cases and therapeutic intervention was possible in four. There was no operative mortality. Because of the importance of an accurate diagnosis in order to avoid inappropriate therapy, together with the relative safety of the technique, computer-directed stereotactic biopsy should be considered in all patients harbouring an intrinsic brain stem mass.


Phosphorus Pentachloride Initiated Functionalization of Silicon Nanocrystals.
Phosphorus pentachloride (PCl5) has long been used to chlorinate hydrocarbons. It has also been applied in silicon surface chemistry to facilitate alkylation via a two-step halogenation/Grignard route. Here we report a study of the reaction of PCl5 with hydride-terminated silicon nanocrystals (H-SiNCs). An examination of the reaction mechanism has allowed us to establish a functionalization protocol that uses PCl5 as a surface radical initiator to introduce alkyl and alkenyl moieties to the surface of H-SiNCs. The reaction proceeds quickly in a single step, at room temperature and the functionalized silicon nanocrystals retained their morphology and crystallinity. The resulting materials exhibited size-dependent photoluminescence that was approximately 3× as bright as that observed for thermally hydrosilylated SiNCs. Furthermore, the absolute PL quantum yield (AQY) was more than double. The high AQY is expected to enable SiNCs to compete with chalcogenide-based quantum dots in various applications.


Lamivudine treatment in patients with hepatitis B virus induced liver cirrhosis.
First studies have suggested a beneficial effect of lamivudine in patients with cirrhosis caused by replicating hepatitis B virus. Whether long-term lamivudine therapy is effective in HBV-related liver cirrhosis patients was prospectively evaluated. Thirty-one patients with hepatitis B virus-related compensated/decompensated cirrhosis, all with quantitative DNA +ve by hybridization (10 HBeAg +ve, 21 anti-HBe +ve), received lamivudine 100 mg/day for average 16.3 (4-34) months. At the end of therapy HBeAg seroconversion was observed in one patient. HBV DNA lost in all patients except two. Albumin levels increased (p<0.05). ALT levels and Child-Pugh-Turcotte scores decreased (p<0.05). Any complication related with liver cirrhosis was not observed during treatment period despite spontaneous ascitic infection in one and hepatic coma in two were occurred before therapy. Only one patient had clinical breakthrough presented by increase in ALT levels and reappearing of HBV DNA during therapy. In patients with cirrhosis caused by replicating hepatitis B virus, prolonged therapy with lamivudine is well tolerated and resulted in improved serum biochemical values and loss of HBV DNA. Clinical improvements may also occur.


Private plans in medicare: another look.
Previous efforts by Congress to expand the role of private plans in Medicare have met with limited success. Although the same fate may befall Medicare Advantage (MA), authorized by the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003, the political environment has changed, and powerful political interests now support Medicare privatization. Only time will tell whether these interests--and the policies they are pursuing--will be sufficient to offset the barriers that historically have limited the role of private plans in Medicare.


Histologic assessment of equivocal cytologic smears.
To determine if the conversion of equivocal cytologic smears into histologic sections would provide additional diagnostic information in those cases in which it was difficult to obtain additional cytologic samples. Over a year, eight equivocal cytologic smears were converted to histologic sections by removing the coverslips, rehydrating the smears, scraping off the smears into centrifuge tubes, making cell blocks, and sectioning and staining the blocks. The histologic sections enabled cell patterns to be studied and special staining (including immunoperoxidase studies) to be performed. In the eight cases studied, the additional information provided by histology led to a definitive diagnosis in six (75%). When cytologic findings are equivocal and it is difficult to obtain additional cytologic samples, conversion of the smears into histologic sections may provide additional information for diagnosis.


Proteomics-inspired precision medicine for treating and understanding multiple myeloma.
Remarkable progress in molecular characterization methods has led to significant improvements in how we manage multiple myeloma (MM). The introduction of novel therapies has led to significant improvements in overall survival over the past 10 years. However, MM remains incurable and treatment choice is largely based on outdated risk-adaptive strategies that do not factor in improved treatment outcomes in the context of modern therapies. This review discusses current risk-adaptive strategies in MM and the clinical application of proteomics in the monitoring of treatment response, disease progression, and minimal residual disease (MRD). We also discuss promising biomarkers of disease progression, treatment response, and chemoresistance. Finally, we will discuss an immunomics-based approach to monoclonal antibody (mAb), vaccine, and CAR-T cell development. It is an exciting era in oncology with basic scientific knowledge translating in novel therapeutic approaches to improve patient outcomes. With the advent of effective immunotherapies and targeted therapies, it has become crucial to identify biomarkers to aid in the stratification of patients based on anticipated sensitivity to chemotherapy. As a paradigm of diseases highly dependent on protein homeostasis, multiple myeloma provides the perfect opportunity to investigate the use of proteomics to aid in precision medicine.


Hepatocellular carcinoma (HCC) and diagnostic significance of A-fetoprotein (AFP).
Alpha-fetoprotein (alpha-fetoprotein, AFP) is a Glycoprotein, belonging to the intriguing class of onco-development protein. Generally designated as tumour marker, AFP is recognized as an important blood component, having specific diagnostic utilities Elevation of its level up to pathological range in adults correlate with the appearance of several malignant and chronic conditions, such as hepatocellular carcinoma (HCC) and chronic liver disease, respectively. To evaluate the diagnostic significance of AFP in HCC, a study was carried out for a period of two years (Jan 2004 to Dec 2005) A brief history of Patients was taken with clinical symptoms and signs and initial diagnosis. Patients admitted in wards or visiting OPDs with diagnosis or suspicions of HCC and additional conditions of Chronic Liver disease (CLDs), hepatitis C (HCV) and hepatitis B viral (HBV) infections, were selected and classified according to gender. When confirmed, their HCC status was evaluated and classified according to clinical condition. In 1012 adults including, males 762 (75.3%) and females 250 (24.7%) patients suspected of or diagnosed with HCC and presence of HBV and HCV infections. Out of 480 males, who depicted elevated AFP levels, 39 (8.13%) were diagnosed with HCC. Similarly, 7 (5.34%) females out of 131 with elevated levels of AFP were diagnosed with HCC. Mean elevated AFP levels in all HCC patients were, 421 +/- 59 microg/ml (range 157-4019 microg/ml) in males and 163 +/- 32 microg/ml (range 101-2341 microg/ml) in females. In males, the overall estimated mean AFP elevated values were analyzed to be 514 microg/ml (range 67-4019 +/- 59 microg/ml,), whereas in females it was 396 +/- 42 microg/ml (range 21-2341 microg/ml). It was also noted that 43 (8.96%) males and 7 (5.34%) female patients, exhibited elevated levels of AFP, however, found negative for HCV and HBV infections. It is concluded that AFP is a significant markers for Hepatocellular carcinoma, helpful in assessing problems in management of HCC and monitoring treatment regiments. In addition, AFP is also an indicator of HCC risks mostly in patients with cirrhosis and HCV/HBV infections.


Small simulators for teaching procedural skills in a difficult airway algorithm.
Difficulty with intubation, ventilation or both is a significant issue for anaesthetists. The American Society of Anesthesiologists' Guidelines for the Management of the Difficult Airway is an algorithm widely used when airway difficulties are encountered. Ideally, anaesthetic trainees should have access to simulators suitable for learning and practising how to manage airway difficulties, but most models have been designed primarily for resuscitation training. The aim of this study was to determine which small airway simulators could be used to practise steps in the Difficult Airway Algorithm (DAA). We identified the essential elements of the DAA relating to endotracheal intubation (laryngoscope, Trachlight and Fastrach), external laryngeal manipulation, dedicated airway devices (LMA, Combitube) and trans-tracheal ventilation using the Enk oxygen flow modulator (Cook). Each element was studied in adult airway models sold for airway management training. The DAA elements were studied in 16 different airway models. No single model achieved our criteria of "good/very realistic" for all elements. All elements of the DAA could be used in the Difficult Airway Trainer Deluxe (MPL) and Bill (VBM/Mallinckrodt) but it would be necessary to acquire at least two trainers to achieve "good/very realistic" in all techniques studied. Anaesthetic departments planning to acquire small simulators for airway management training should undertake a training-needs analysis and apply this to the performance characteristics of the simulators. Generally, at least two airway training models will be needed to teach all steps of the DAA effectively.


Empathic perceptions of nursing students: self-reported and actual ability.
Clearly, one of the goals of nursing education is to enhance the empathic functioning of nursing students. In this study we examined one major component of empathic functioning--accuracy of empathic perceptions--in both undergraduate (n = 66) and graduate nursing students (n = 50) We predicted that actual ability (Kagan's Affective Sensitivity Scale) and self-perceived ability would vary as a positive function of educational level. The results supported the first prediction, even when the effects of the subjects' age and amount of prior nursing experience were controlled. Self-perceived ability, however, was not reliably related to educational level, although it did relate to actual ability. Compared with students in other "helping" professions, the students in this study appeared relatively empathic. Finally, students' perceptions of their difficulty in detecting and handling other particular feeling states suggest that nursing needs to take a more "affect-specific" approach to empathic functioning.


Immunobiology of fibrinogen. Emergence of neoantigenic expressions during physiologic cleavage in vitro and in vivo.
Physiological degradation of fibrinogen by plasmin leads to a recognized series of intermediate and stable terminal cleavage fragments and is associated with complex modulation and progressive loss of native antigenic expressions. Early in association with progressive plasmin cleavage, a stable cleavage-associated neoantigen, present in the D-fragment region of the molecule, is exposed in vitro and can be recognized by competitive inhibition radioimmunoassay with specific antiserum. It is demonstrated that there is an approximate equimolar expression of the cleavage-associated neoantigen. fg-D(neo), on the X-, Y-, and D-fragments and no recognizable (< 10(-3)) expression by fibrinogen or by the E-fragment. The X-fragment contains two D regions in respect to total D-fragment-associated antigenic expressions but unitary expression of fg-D(neo) is observed. The Y-fragment appears to contain one D-fragment region in respect to total D-fragment-associated antigens and exhibits close to unitary expression of fg-D(neo). Terminal cleavage digests containing the D- and E-fragments exhibit more than 10-fold greater native fibrinogen antigenic expression than the sum of the constituent fragments. This suggests the presence of a non-covalently associated native complex of the D- and E-fragments, and implies contiguity of the D- and E-fragments in the native fibrinogen molecule. The cleavage-associated neoantigen, fg-D(neo), is also generated in vivo and is generically demonstrable in the plasma of patients with various forms of in vivo fibrinolysis. These studies offer a precise immunochemical system, based upon defined molecular events, for the investigation of physiological and pathophysiological cleavage of fibrinogen. By contrast with other approaches to the assay of in vitro or in vivo cleavage of fibrinogen, assay of the cleavage-associated neoantigen fg-D(neo) is specific, sensitive, directly yields the molar concentration of all cleavage fragments except E, and is directly applicable to plasma.


Agriculture and hot temperatures interactively erode the nest success of habitat generalist birds across the United States.
Habitat conversion and climate change are fundamental drivers of biodiversity loss worldwide but are often analyzed in isolation. We used a continental-scale, decades-long database of more than 150,000 bird nesting attempts to explore how extreme heat affects avian reproduction in forests, grasslands, and agricultural and developed areas across the US. We found that in forests, extreme heat increased nest success, but birds nesting in agricultural settings were much less likely to successfully fledge young when temperatures reached anomalously high levels. Species that build exposed cup nests and species of higher conservation concern were particularly vulnerable to maximum temperature anomalies in agricultural settings. Finally, future projections suggested that ongoing climate change may exacerbate the negative effects of habitat conversion on avian nesting success, thereby compromising conservation efforts in human-dominated landscapes.


Sampling-based real-time motion planning under state uncertainty for autonomous micro-aerial vehicles in GPS-denied environments.
This paper presents a real-time motion planning approach for autonomous vehicles with complex dynamics and state uncertainty. The approach is motivated by the motion planning problem for autonomous vehicles navigating in GPS-denied dynamic environments, which involves non-linear and/or non-holonomic vehicle dynamics, incomplete state estimates, and constraints imposed by uncertain and cluttered environments. To address the above motion planning problem, we propose an extension of the closed-loop rapid belief trees, the closed-loop random belief trees (CL-RBT), which incorporates predictions of the position estimation uncertainty, using a factored form of the covariance provided by the Kalman filter-based estimator. The proposed motion planner operates by incrementally constructing a tree of dynamically feasible trajectories using the closed-loop prediction, while selecting candidate paths with low uncertainty using efficient covariance update and propagation. The algorithm can operate in real-time, continuously providing the controller with feasible paths for execution, enabling the vehicle to account for dynamic and uncertain environments. Simulation results demonstrate that the proposed approach can generate feasible trajectories that reduce the state estimation uncertainty, while handling complex vehicle dynamics and environment constraints.


The diverse effects of a Chinese medicine, Qing Nao Yi Zhi Fang, on the proliferation of human arterial smooth muscle cells and endothelial cells.
Qing Nao Yi Zhi Fang (QNYZ), a Chinese medicine, has been developed as a drug for the prevention and treatment of vascular dementia. We examined the effects of QNYZ-treated serum and QNYZ on the proliferation of human arterial smooth muscle cells (SMCs) and endothelial cells (ECs). SMCs did not grow in a medium containing 10% QNYZ serum. QNYZ also completely inhibited the proliferation of SMCs at higher concentrations (500-1000 microg/ml), although no detectable inhibitory activity on the SMC proliferation was observed at lower concentrations (100-200 microg/ml). In contrast, QNYZ (250-500 microg/ml) significantly stimulated the proliferation of ECs and prostacyclin production in ECs. These results suggest that QNYZ may have suppressive effects on the development of intimal thickening in atherosclerosis and after arterial wall injury.


Challenges in bridging the gap between protein structure prediction and functional interpretation.
The rapid evolution of protein structure prediction tools has significantly broadened access to protein structural data. Although predicted structure models have the potential to accelerate and impact fundamental and translational research significantly, it is essential to note that they are not validated and cannot be considered the ground truth. Thus, challenges persist, particularly in capturing protein dynamics, predicting multi-chain structures, interpreting protein function, and assessing model quality. Interdisciplinary collaborations are crucial to overcoming these obstacles. Databases like the AlphaFold Protein Structure Database, the ESM Metagenomic Atlas, and initiatives like the 3D-Beacons Network provide FAIR access to these data, enabling their interpretation and application across a broader scientific community. Whilst substantial advancements have been made in protein structure prediction, further progress is required to address the remaining challenges. Developing training materials, nurturing collaborations, and ensuring open data sharing will be paramount in this pursuit. The continued evolution of these tools and methodologies will deepen our understanding of protein function and accelerate disease pathogenesis and drug development discoveries.


Functional magnetic resonance imaging of Broca's area during internal speech.
Conventional gradient-echo magnetic resonance imaging (MRI) at 4 Tesla was used successfully to study the activity of Broca's area during internal speech word generation in healthy right-handed volunteers. Activity was demonstrated in the internal gray matter surrounding the ascending ramus of the lateral sulcus, deep to the cortical surface representation of Broca's area, in all the subjects. These studies demonstrate the capability of functional MRI to non-invasively map language related cognitive functions. Such functional mapping has value for both the study of basic neuroscience and neurosurgical planning.


Ultrastructural and immunohistochemical observations of a true malignant mixed tumor (carcinosarcoma) of the tongue.
True malignant mixed tumor (TMMT) of salivary glands, with both carcinomatous and sarcomatous components, is exceedingly rare. We offer a case of TMMT in a 79-yr-old man, which may represent the first report example of this unusual neoplasm arising in the tongue. The carcinomatous component was mainly of solid basaloid carcinoma with focal glandular differentiation, while the sarcomatous component was composed of pleomorphic elements such as chondrosarcoma, myxosarcoma and fibrosarcoma. Carcinoma cells at the periphery of solid nests occasionally merged into these sarcomatous elements. Immunohistochemically, basaloid carcinoma cells showed positive reaction for both low molecular weight cytokeratin and S-100 protein, whereas carcinoma cells lining ductal spaces were positive for a wide spectrum of keratin and EMA. The sarcomatous elements revealed the presence of vimentin and S-100 protein. Ultrastructurally, basal lamina-like material and/or mucoid precipitates often accumulated separating the tumor cells from each other singly or into a few cell group. Some sarcomatous cells assumed the myoepithelial features, such as the presence of microfilament bundles with dense bodies and pinocytotic vesicles along the cell periphery. These findings may indicate that TMMT shares a common histogenesis with pleomorphic adenoma.


Drainage of the subretinal fluid and injection of saline solution into the vitreous body.
In a group of 250 cases operated upon for retinal detachment, drainage of the subretinal fluid was carried out in 96%. Since in 54 cases, i.e. 22%, a large quantity of subretinal fluid was evacuated, saline solution was injected into the vitreous. The following complications due to drainage were noted: intraocular haemorrhages (16%), incarceration of the retina (1%) and temporary iridocyclitis (2%). None of these complications prevented reattachment. In 54 cases in which injection of saline solution into the vitreous was carried out, we have noted: temporary occlusion of the central retinal artery (5 cases), temporary cloudiness in the vitreous body (2 cases) and traumatic cataract (1 case). The injection of saline solution into the vitreous was well tolerated. Although the complications due to drainage are rather numerous (intraocular infection and haemorrhages, incarceration of retina, secondary retinal hole, glial proliferation in the vitreous, dehiscence at the place of drainage), these complications rarely occur if the drainage is carried out in a proper manner. Despite the fact that drainage and injection of saline solution into the vitreous do not cause more severe complications, however, we consider that the method of avoiding drainage and internal tamponage, whenever it is possible, represents a fully justified trend.


The cost of burn care and implications for the future on quality of care.
The high cost of health care has become a nationwide concern and there are several national initiatives under way to reduce the rate of increase of these costs. Among the most recent initiatives has been the introduction of Medicare reimbursement based upon Diagnostic Related Groups (DRGs). This paper presents a retrospective analysis of the costs of care of burned patients admitted to the University of Alabama at Birmingham Burn Center and a profile of the financial impact of DRGs. Costs for burned patients were twice as high as for the average patient in the hospital and increased at a faster rate. Since 1977 the proportion of indigent patients and patients with very poor third-party coverage has greatly increased and those with good or excellent third-party coverage has decreased. If the care for Medicare patients had been reimbursed on the bases of DRG rates in 1982, payments would have exceeded costs by $2,981 but would have been $88,399 less than charges. In 1983, if the care for Medicare patients had been reimbursed on the bases of DRG rates, the payment would have been $409,629 less than costs and $634,583 less than charges. This very unfavorable reimbursement is because DRG reimbursement is essentially a flat rate and for long lengths of stay costs are much greater than reimbursements. Specific policies on methods to correct this discrepancy are suggested.


Analysis by pulsed-field gel electrophoresis of DNA double-strand breakage and repair in Deinococcus radiodurans and a radiosensitive mutant.
Double-strand break (dsb) induction and rejoining after ionizing radiation was analysed in Deinococcus radiodurans and a radiosensitive mutant by pulsed-field gel electrophoresis. Following 2 kGy, migration of genomic DNA (not restriction cleaved) from the plug into the gel was extensive, but was not observed after 90 min postirradiation recovery. By this time D. radiodurans chromosomes were intact, as demonstrated by restoration of the Not I restriction cleavage pattern of 11 bands, which we found to be the characteristic pattern in unirradiated cells. Following the higher exposure of 4 kGy, dsb rejoining took approximately 180 min, twice as long as required following the 2 kGy exposure. Restoration of dsb in the radiosensitive mutant strain 112, which appears to be defective in recombination, was markedly retarded at both 2 and 4 kGy. The Not I restriction fragments of wild-type D. radiodurans and the radiosensitive mutant were identical, totaling 3.58 Mbp, equivalent to 2.36 x 10(9) daltons per chromosome.


Postpartum domperidone use in British Columbia: a retrospective cohort study.
Domperidone is commonly used off-label to stimulate milk production in mothers who have low milk supply. The aim of this study was to describe trends, patterns and determinants of postpartum domperidone use. This is a retrospective, population-based study involving all women with a live birth between Jan. 1, 2002, and Dec. 31, 2011, in the province of British Columbia. We examined administrative data sets containing person-specific information on filled prescriptions and use of medical services, and we used logistic regression to examine associations between domperidone use and maternal characteristics. The study population consisted of 225 532 women with 320 351 live births. The prevalence of postpartum domperidone use more than doubled between 2002 and 2011. In 2011, 1 in 3 women with a preterm birth and 1 in 5 women with a full-term birth were prescribed domperidone in the first 6 months postpartum. Women who were older, had a higher body mass index, had a chronic disease, were first-time mothers, delivered more than 1 baby (multiple pregnancy), had a preterm birth or had a cesarian delivery were more likely to fill a postpartum domperidone prescription. We found an increase in postpartum domperidone use over a 10-year period. More research is needed on maternal and infant health outcomes.


The significance of HPV in the follow-up period after treatment for CIN.
High-risk anogenital human papillomavirus (HPV) infections are causally related to cervical cancer. Successful treatment of cervical intraepithelial neoplasia (CIN) results in complete eradication of HPV in most cases. There is an increasing interest regarding the role of HPV testing in the follow-up period after treatment for CIN. This retrospective study includes 107 women who underwent conization for histologically verified CIN. All of them had HPV testing pre- and postoperatively. HPV testing was carried out using a hybrid capture assay (HC2). The mean follow-up period was 21.4 months (range 2-76 months). The data were analyzed with respect to success of conization, HPV persistence/recurrence and CIN recurrence. Sensitivity, specificity and negative predictive value (NPV) of HPV testing were assessed and compared to the cytological results. Preoperatively, 97 of 107 women were HPV positive. Ninety-seven conizations showed negative resection margins with 86 women becoming HPV negative. In the following months, nine of these HPV negative women became HPV positive again. Out of ten conizations with positive resection margins, six women became HPV negative. Recurrent CIN 2/3 lesions were observed in 11 women, nine of whom had persistent positive HPV testing throughout the entire study period. Regarding CIN recurrence HPV testing showed a sensitivity of 93%, a specificity of 85% and a NPV of 99%. The sensitivity of HPV testing concerning persistent or recurrent CIN as well as the NPV are high. The present data suggest that HPV testing should be integrated in a follow-up algorithm after treatment for CIN by conization.


In vitro activities of 36 antimicrobial agents against clinically isolated Bacteroides fragilis.
Thirty-six antimicrobial agents were evaluated for in vitro activities against 100 clinical isolates of Bacteroides fragilis. The minimal inhibitory concentration (MIC) of each agent for each isolate was determined by the agar dilution method. Among 25 beta-lactam antibiotics, the most active agent was imipenem with an MIC90 and a geometric mean of 1 and 0.15 micrograms/ml, respectively; followed by ticarcillin-clavulanic acid, and amoxicillin-clavulanic acid. Ampicillin-sulbactam, piperacillin-tazobactam, moxalactam, and flomoxef were the next most active agents. Piperacillin, ticarcillin, ceftizoxime, cefotaxime, cefuzonam, cefoxitin, and cefmetazole were equally active with the MIC50s ranging from 4 to 16 micrograms/ml, and MIC90s ranging from 32 to greater than or equal to 256 micrograms/ml. The remaining 10 beta-lactam antibiotics, ampicillin, amoxicillin, cefazolin, cefuroxime, cefoperazone, cefmenoxime, ceftazidime, cefpirome, aztreonam, and carumonam were less active. All isolates were resistant to cefotiam at a low breakpoint. Among 6 quinolones, ciprofloxacin was the most active agent with an MIC50 and an MIC90 of 4 and 16 micrograms/ml, respectively. All isolates were resistant to nalidixic acid, pipemidic acid, cinoxacin, enoxacin, and norfloxacin. Among 5 frequently used agents, chloramphenicol, ornidazole, and metronidazole were the most effective agents which inhibited 100% of the isolates at 8, 2, and 2 micrograms/ml, respectively; while clindamycin and minocycline had less activity.


Use of allogeneic apheresis stem cell products as an interlaboratory proficiency challenge.
AABB Standards requires that laboratories participate in a proficiency test (PT) program for critical analytes. Institutions can purchase commercial PT materials; however, PT can also be performed through interlaboratory exchange. We investigated the utility of allogeneic hematopoietic progenitor cell apheresis (HPC-A) products as an interlaboratory PT challenge for total nucleated cell count (TNC) and CD34 assessment. Three-year retrospective and comparative review of unrelated allogeneic HPC-A products received by the University of Michigan between January 2011 and December 2013. Internal TNC and CD34 count were compared to the external collecting facility by paired t test and linear regression. The absolute and percent difference between external and internal counts and 95% limits of agreeability (95% LA) were determined. Results were analyzed relative to donor center location (international, domestic), time zone (domestic), and calendar year. There was a strong correlation between internal and external TNC, regardless of donor center location or year. For CD34, there was a good correlation between centers (R = 0.88-0.91; slope = 0.95-0.98x) with a median difference of -1% (95% LA, -50%, +47%). This was considerably better than commercial PT challenges, which showed a persistent negative bias for absolute CD34 and CD3 counts. Allogeneic HPC-A products represent an interlaboratory PT exchange for all critical analytes, including TNC and CD34 count, cell viability, and sterility. Allogeneic HPC-A products, which are fresh and transported under validated conditions, are less subject to preanalytical variables that may impact commercial PT samples such as aliquoting and sample homogeneity, commercial additives, and sample stability during manufacturing and transport.


Liquiritin from Radix Glycyrrhizae Protects Cardiac Mitochondria from Hypoxia/Reoxygenation Damage.
The purpose of this study was to evaluate the protective effect of liquiritin (LIQ) from Radix Glycyrrhizae on cardiac mitochondria against hypoxia/reoxygenation (HR) injury. H9C2 cells were subject to the HR model. LIQ purified from Radix Glycyrrhizae (purity > 95%) was administrated to reoxygenation period. Cell viability, mitochondrial mass, mitochondrial membrane potential, reactive oxygen species, and mitochondrial Ca2⁺ level were then assessed by using Cell Counting kit-8 and suitable fluorescence probe kits. LIQ administration remarkably reduced the rate of HR damage via increasing H9C2 cell viability level and preserving mitochondria after HR. Particularly, 60 μM of LIQ posthypoxic treatment markedly reduced cell death in HR-subjected H9C2 cell groups (p < 0.05). Interestingly, posthypoxic treatment of LIQ significantly prevented the loss of mitochondrial membrane potential, the decrease in mitochondrial mass, the increase in reactive oxygen species production, and the elevation of mitochondrial Ca2⁺ level in HR-treated H9C2 cells. The present study provides for the first time the cardioprotective of LIQ posthypoxic treatment via reducing H9C2 cell death and protecting cardiac mitochondria against HR damage.


Application of the Human Intestinal Tract Chip to the non-human primate gut microbiota.
The human intestinal microbiota is responsible for various health-related functions, and its diversity can be readily mapped with the 16S ribosomal RNA targeting Human Intestinal Tract (HIT) Chip. Here we characterise distal gut samples from chimpanzees, gorillas and marmosets, and compare them with human gut samples. Our results indicated applicability of the HITChip platform can be extended to chimpanzee and gorilla faecal samples for analysis of microbiota composition and enterotypes, but not to the evolutionary more distant marmosets.


Intermethod variability in TSH-receptor antibody measurement: implication for the diagnosis of Graves disease and for the follow-up of Graves ophthalmopathy.
We compared the analytical and clinical performance of 3 porcine thyroid receptor antibody (TRAb) methods (1 second- and 2 new third-generation systems) with the conventional TRAb assay based on the human recombinant TSH receptor (hTRAK). We obtained sera from 86 patients with untreated Graves disease (GD) and 71 healthy controls. We measured TRAb concentrations by radioreceptor assay using the hTRAK (Brahms) or the porcine TSH receptor (pRRA) from Beckman-Coulter, by electrochemiluminescence immunoassay (ECLIA) with the Elecsys/Cobas (Roche), and by ELISA using the Medizym TRAb clone (Medipan). Between-run assay imprecision was < or =10% and < or =7.6% for hTRAK and ECLIA, but reached 14% and 14.9% for ELISA and pRRA, respectively. Maximal specificity and sensitivity close to 100% were obtained for hTRAK, ECLIA, and ELISA. pRRA failed to detect positive TRAbs in 5 GD patients. Although calibrated against the same reference standard 90/672, the assays displayed a high intermethod variability. The results were significantly higher by ECLIA and lower by ELISA and pRRA compared with hTRAK. Patients with ophthalmopathy had higher TRAb results by ELISA and pRRA than those without eye disease. Second- and third-generation TRAb assays had similar diagnostic sensitivities in the diagnostic evaluation of GD. Despite the use of the same reference standard for calibration, high intermethod variability in TRAb assay results was seen in untreated GD patients. Assay harmonization is necessary for correct interpretation in the follow-up of Graves ophthalmopathy.


Role of spinal 5-HT receptors in cutaneous hypersensitivity induced by REM sleep deprivation.
Previous studies indicate that rapid eye movement (REM) sleep deprivation facilitates pain sensitivity. Since serotoninergic raphe neurons are involved both in regulation of sleep and descending pain modulation, we studied whether spinal 5-HT receptors have a role in sleep deprivation-induced facilitation of pain-related behavior. REM sleep deprivation of 48h was induced by the flower pot method in the rat. The pain modulatory influence of various serotoninergic compounds administered intrathecally was assessed by determining limb withdrawal response to monofilaments. REM sleep deprivation produced a marked hypersensitivity. Sleep deprivation-induced hypersensitivity and normal sensitivity in controls were reduced both by a 5-HT(1A) receptor antagonist (WAY-100635) and a 5-HT(2C) receptor antagonist (RS-102221). An antagonist of the 5-HT(3) receptor (LY-278584) failed to modulate hypersensitivity in sleep-deprived or control animals. Paradoxically, sensitivity in sleep-deprived and control animals was reduced not only by a 5-HT(1A) receptor antagonist but also by a 5-HT(1A) receptor agonist (8-OHDPAT). The results indicate that serotoninergic receptors in the spinal cord have a complex role in the control of sleep-deprivation induced cutaneous hypersensitivity as well as baseline sensitivity in control conditions. While endogenous serotonin acting on 5-HT(1A) and 5-HT(2C) receptors may facilitate mechanical sensitivity in animals with a sleep deprivation-induced hypersensitivity as well as in controls, increased activation of spinal 5-HT(1A) receptors by an exogenous agonist leads to suppression of mechanical sensitivity in both conditions. Spinal 5-HT(3) receptors do not contribute to cutaneous hypersensitivity induced by sleep deprivation.


Fracture prediction for the femoral neck using finite element models.
Fracture of the femoral neck is an important clinical, social and economic topic. Prediction in subjects who are at risk for this type of fracture has been the object of numerous studies. Nonetheless, the methods of classification based on densitometric indicators alone have shown poor accuracy. It is the purpose of this study to propose a method to obtain an estimate of the resistance of the proximal femur, and to improve accuracy in prediction in subjects who are at risk for fracture. Based on the densitometric dataset alone, a bidimensional finite element model was developed that takes into account the distribution of density together with the femoral anatomy and the typical conditions of trauma. The model was applied to a group of preliminary osteoporotic patients. The statistical classification showed an increase in accuracy by 13%, as compared to a classification based on densitometric indicators alone.


Candidate genes for migration do not distinguish migratory and non-migratory birds.
Migratory traits in birds have been shown to have a strong heritable component and several candidate genes have been suggested to control these migratory traits. To investigate if the genetic makeup of one or a set of these candidate genes can be used to identify a general pattern between migratory and non-migratory birds, we extracted genomic sequence data for 25 hypothesised candidate genes for migration from 70 available genomes across all orders of Aves and characterised sequence divergence between migratory and non-migratory phenotypes. When examining each gene separately across all species, we did not identify any genetic variants in candidate genes that distinguished migrants from non-migrants; any resulting pattern was driven by the phylogenetic signal. This was true for each gene analysed independently, but also for concatenated sequence alignments of all candidate genes combined. We also attempted to distinguish between migrant and non-migrants using structural features at four candidate genes that have previously been reported to show associated with migratory behaviour but did not pick up a signal for migratory phenotype here either. Finally, a screen for dN/dS ratio across all focal candidate genes to probe for putative features of selection did not uncover a pattern, though this might not be expected given the broad phylogenetic scale used here. Our study demonstrates the potential of public genomic data to test for general patterns of migratory gene candidates in a cross-species comparative context, and raise questions on the applicability of candidate gene approaches in a macro-evolutionary context to understand the genetic architecture of migratory behaviour.