Microdilution and agar replica identification test systems.
A number of microdilution and agar-replicating systems are currently available for the rapid, accurate identification of common bacterial pathogens. These systems can be highly automated for large clinical laboratories or used manually for small laboratories.


Component-specific surface and physiological activity in bovine-derived lung surfactants.
Composition, surface activity and effects on pressure-volume (P-V) mechanics are examined for lavaged calf lung surfactant (LS) and the clinical exogenous surfactants Infasurf and Survanta. Lavaged LS and Infasurf had closely-matching compositions of phospholipids and neutral lipids. Survanta had higher levels of free fatty acids and triglycerides consistent with its content of added synthetic palmitic acid and tripalmitin. Infasurf and Survanta both contained less total protein than LS because of extraction with hydrophobic solvents, but the total protein content relative to phospholipid in Survanta was about 45% lower than in Infasurf. This difference was primarily due to surfactant protein (SP)-B, which was present by ELISA at a mean weight percent relative to phospholipid of 1.04% in LS, 0.90% in Infasurf, and 0.044% in Survanta. Studies on component fractions separated by gel permeation chromatography showed that SP-B was a major contributor to the adsorption, dynamic surface activity, and P-V mechanical effects of Infasurf, which approached whole LS in magnitude. Survanta had lower adsorption, higher minimum surface tension, and a smaller effect on surfactant-deficient P-V mechanics consistent with minimal contributions from SP-B. Addition of 0.05% by weight of purified bovine SP-B to Survanta did not improve surface or physiological activity, but added 0.7% SP-B improved adsorption, dynamic surface tension lowering, and P-V activity to levels similar to Infasurf. The SP-B content of lung surfactants appears to be a crucial factor in their surface activity and efficacy in improving surfactant-deficient pulmonary P-V mechanics.


CD79A work as a potential target for the prognosis of patients with OSCC: analysis of immune cell infiltration in oral squamous cell carcinoma based on the CIBERSORTx deconvolution algorithm.
To analyze the abundance of infiltrating tumor immune cells in patients with oral squamous cell carcinoma (OSCC) and to search for potential targets that can predict patient prognosis. A total of 400 samples from 210 patients with OSCC were collected using The Cancer Genome Atlas (TCGA) database. CIBERSORTx was used to evaluate the infiltration abundance of tumor immune cells. Potential target genes were searched to predict patient prognosis through case grouping, differential analysis, and enrichment analysis. Surgical excisional tissue sections of patients with oral squamous cell carcinoma admitted to the Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital of Shantou University Medical College, from 2015 to 2018 were collected and followed up. The CIBERSORTx deconvolution algorithm was used to analyze the infiltration abundance of immune cells in the samples. Cases with a high infiltration abundance of naive and memory B lymphocytes improved the prognosis of OSCC patients. The prognosis of patients with low CD79A expression was significantly better than that of patients with high CD79A expression. CD79A can predict the infiltration abundance of B lymphocytes in the tumor microenvironment of patients with OSCC. CD79A is a potential target for predicting the prognosis of patients with OSCC. This study provides novel ideas for the treatment of OSCC and for predicting patient prognosis.


The effect of distal radius fractures involving the distal radioulnar articular joint on forearm rotation.
The objective of this study was to predict the function of the forearm rotation on the basis of the articular surface of the sigmoid notch from three-dimensional reconstruction images. We retrospectively reviewed patients who underwent volar plate fixation for intra-articular distal radius fractures (DRFs) in our institution between January 2017 and July 2019. The 3D image of the sigmoid notch on the fractured distal radius was reconstructed and looked up from the ulnar view to determine the existence of gaps or steps. Patients with or without gaps/steps on the sigmoid notch were included in the case group or control group, respectively. The patients' basic data and postoperative data were collected and compared. A total of 81 patients were included. There were 33 patients in the case group, and 48 patients in the control group. There was no significant difference between the two groups at baseline. The total range of motion (ROM) of rotation in the case group and control group was 130.3 ± 6.2° and 145.3 ± 6.7°, respectively (P < 0.001). The percentage of rotation ROM of contralateral limb in the case group and control group was 72.3 ± 3.1% and 80.7 ± 3.6%, respectively (P < 0.001). VAS during forearm rotation was 2.1 ± 0.7 in the case group, which is significantly higher than that in the control group (1.5 ± 0.5, P < 0.001). This study proposed a new method to assess the articular surface of the sigmoid notch which is based on 3D reconstruction images. With the assistance of this method, we found that gaps or steps on the sigmoid notch not only limit forearm pronation rotation and supination rotation, but also cause apparent wrist pain during forearm rotation movement and poor wrist ability.


Expert consensus on relevant risk predictors for the occurrence of osteoporotic fractures in specific clinical subgroups - Delphi survey.
There is an ongoing discussion about incorporating additional risk factors to established WHO fracture risk assessment tool (FRAX) to improve the prediction accuracy in clinical subgroups. We aimed to reach an expert consensus on possible additional predictive parameters for specific clinical subgroups. Two-round modified Delphi survey: We generated a shortlist of experts from the authors' lists of the pertinent literature and complemented the list with experts known to the authors. Participants were asked to name possible relevant risk factors besides the FRAX-parameters for the occurrence of osteoporotic fractures. Experts specified these possible predictors for specific subgroups of patients. In the second round the expert panel was asked to weight each parameter of every subgroup assigning a number between one (not important) to ten (very important). We defined the threshold for an expert consensus if the interquartile range (IQR) of a predictor was ≤2. The cut-off value of the median attributed weights for a relevant predictor was set at ≥7. Eleven experts of seven countries completed both rounds of the Delphi. The participants agreed on nine additional parameters for seven categories. For the category "secondary osteoporosis", "older adults" and "nursing home patients", there was a consensus that history of previous falls was relevant, while for men and postmenopausal women, there was a consensus that the spine fracture status was important. For the group "primary and secondary osteoporosis" the experts agreed on the parameters "high risk of falls", "lumbar spine bone mineral density (BMD)" and "sarcopenia". This Delphi survey reached a consensus on various parameters that could be used to refine the currently existing FRAX for specific clinical situations or patient groups. The results may be useful for studies aiming at improving the predictive properties of instruments for fracture prediction.


The association between maternal anemia during pregnancy and preterm birth.
Maternal anemia is one of the most serious health problems during pregnancy. The causes of anemia include iron deficiency, parasitic diseases, micronutrient deficiencies, and hereditary hemoglobinopathies. Because the reported association between maternal anemia and preterm labor in different studies is varied depending on the month of pregnancy this study aims to determine this relationship after adjustment for potential confounders. A case-control study was conducted among 801 pregnant women (267 cases and 534 controls) in Sardashat, Iran from October 2012 to October 2013. Hemoglobin (Hb) values were measured for all women participating in the study during the first and second trimesters of pregnancy, and the average Hb values were presented. Statistical analyzes were performed with logistic regression. The mean age of participants was 26.4 ± 5.25 years for the case group and 27.2 ± 6.51 years for the control group. Preterm birth was associated with maternal anemia during pregnancy [aOR = 2.69 (95% CI; 1.46 to 4.95)] even after adjusting for confounding effects including maternal age, history of abortion [aOR = 2.41 (95% CI; 1.42 to 4.08)], history of preterm birth [aOR = 11.38 (95% CI; 3.48 to 37.22)], obesity (aOR: 3.441; CI95%: 1.18-10.06), parity [aOR = 0.42 (95% CI; 0.25 to 0.69)], preeclampsia/eclampsia [aOR = 6.08 (95% CI; 2.64 to 14)], and GDM [aOR = 4.80 (95% CI; 2.02 to 11.41)]). Early detection and adequate treatment of anemia during pregnancy can help reduce the prevalence of preterm birth.


Determination of monoamines in brain nuclei by high performance liquid chromatography with electrochemical detection: young vs. middle aged rats.
A previously described high performance liquid chromatographic method for simultaneously measuring norepinephrine, dopamine, serotonin and 5-hydroxyindole acetic acid has been modified to permit analysis of the monoamines in microdissected brain nuclei from a single rat. Results of measurements in 12 nuclei of young and middle aged male rats are presented.


Investigation of Cerebellar Abiotrophy (CA), Lavender Foal Syndrome (LFS), and Severe Combined Immunodeficiency (SCID) Variants in a Cohort of Three MENA Region Horse Breeds.
Genetic disorders in horses are mostly fatal or usually cause significant economic losses for breeders and owners. Here we studied a total of 177 Arabian, Barb and Arab-Barb horses from the Middle East and North Africa (MENA) using Sanger Sequencing and PCR-ACRS (polymerase chain reaction-artificially created restriction site) approaches to examine the genetic disorders in the studied horse breeds. We identified the genetic variations related to Cerebellar Abiotrophy (CA), Severe Combined Immunodeficiency (SCID) occurrence, and the studied population was free of the mutant allele determined Lavender Foal Syndrome (LFS). Overall, presented data showed that 15 of the studied horses are carriers of two genetic disorders; the investigated horse population showed that five Arabian horses were heterozygous for the CA-associated SNP (rs397160943). The SCID-deletion TCTCA within PRKDC was detected in ten horses (nine Arabian horses and one Arab-Barb horse). This investigation shows the importance of testing these breeds for genetic disorders to avoid further spread of deleterious variants.


Low relapse with oral antibiotics and two-stage exchange for late arthroplasty infections in 40 patients after 2-9 years.
Exchange surgery in late arthroplasty infection is directed against bacteria adhering to implants. Therapies based on antibiotics that are effective intracellularly have been proposed recently. We have combined both strategies to improve the cure rate. 40 consecutive patients (16 hips, 24 knees) were diagnosed with late arthroplasty infection. The organisms isolated were 35 Staphylococcus, 19 of which were methicillin-resistant, 4 Enterococcus, 6 Gram-negative bacilli, and 4 Corynebacterium. The infections were managed by a combined therapy consisting of two-stage exchange surgery and two oral intracellularly-effective antibiotics. The antibiotics were selected according to bacterial sensitivity and intracellular and biofilm effectiveness. Second re-implantation surgery was delayed until clinical and analytical normalization. Patients were in hospital for only 1 week after each surgery, and were followed up prospectively on an outpatient basis (2-9 years). Cure of the infection was defined as absence of clinical, serological, and radiographic signs of infection during the whole follow-up. The infection was resolved in 38/40 patients (15/16 hips and 23/24 knees). Oral antibiotics that are effective intracellularly in combination with two-stage exchange surgery is a promising alternative for treating late arthroplasty infections. Oral antibiotics shorten hospitalization and reduce patient discomfort.


[The diagnosis of myocardial infarction in the presence of disorders of ventricular activation for right endoventricular pacing and left bundle branch block (author's transl)].
The Authors have studied the vectocardiogram in left bundle branch block, right endoventricular pacing, myocardial infarction and right endoventricular pacing, myocardial infarction and left bundle branch block. Vectocardiographic loop analysis allows the diagnosis of myocardial infarction both in the presence of endoventricular pacing and in the presence of left bundle branch block.


Severe Leg Pain Following Spinal Cord Stimulator Implantation - A Case Report.
Following spinal cord stimulator (SCS) implantation, postoperative pain is commonly incisional or neuropathic from neurological damage. Occasionally, this new pain may mimic symptoms caused by preexisting pathology. This article presents a case of immediate, severe, postoperative leg pain secondary to a lower extremity deep vein thrombosis (DVT) and subsequent pulmonary embolism after percutaneous SCS implantation for failed back syndrome. The risk factors of DVT after spine surgery and perioperative prophylaxis are further discussed with a brief literature review. LEVEL OF EVIDENCE: V.


An autopsy case of disseminated mucormycosis in a neutropenic patient receiving chemotherapy for the underlying solid malignancy.
Mucormycosis is a rare, opportunistic infection caused by fungi of the order Mucorales, class Zygomycetes. These fungi produce fatal opportunistic infections in immunocompromised patients, especially in those with severe neutropenia. Recently, mucormycosis has become more widespread, because potent, myelosuppressive chemotherapies are performed more often than before. Nevertheless, this infection rarely occurs in patients with solid malignancies. Here, we describe an autopsy case of disseminated mucormycosis in a neutropenic patient who was receiving chemotherapy for an underlying solid malignancy. A 31-year-old Japanese man received cytotoxic chemotherapy with etoposide for the pulmonary metastasis of a secondary malignant fibrous histiocytoma. This patient had long been treated with chemotherapeutic agents for this solid cancer and for the preceding eosinophilic granuloma, both of which were highly resistant to the therapy. During the treatment with etoposide, his neutrophil count declined to less than 100/microl. He presented with high fever and severe dyspnea. Pneumonia was highly suspected. The chemotherapy was discontinued, and granulocyte colony-stimulating factor was administered. Although the neutrophil count recovered, the pneumonia progressed. The patient experienced respiratory failure and died 17 days after the onset of this episode. An autopsy revealed dissemination of mucormycosis not only in the lungs but also in the liver, the spleen, the kidney, and in the digestive tract. The therapy-related severe neutropenia, and the probable impairment of the immune system, because of the previous chemotherapies, would have been responsible for this fatal infection.


Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor.
Despite broad appreciation of their clinical utility, it has been unclear how vitamin B12 and folic acid (FA) function at the molecular level to directly prevent their hallmark symptoms of deficiency like anemia or birth defects. To this point, B12 and FA have largely been studied as cofactors for enzymes in the one-carbon (1C) cycle in facilitating the de novo generation of nucleotides and methylation of DNA and protein. Here, we report that B12 and FA function as natural antagonists of aryl hydrocarbon receptor (AhR). Our studies indicate that B12 and FA bind AhR directly as competitive antagonists, blocking AhR nuclear localization, XRE binding, and target gene induction mediated by AhR agonists like 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 6-formylindolo[3,2-b]carbazole (FICZ). In mice, TCDD treatment replicated many of the hallmark symptoms of B12/FA deficiency and cotreatment with aryl hydrocarbon portions of B12/FA rescued mice from these toxic effects. Moreover, we found that B12/FA deficiency in mice induces AhR transcriptional activity and accumulation of erythroid progenitors and that it may do so in an AhR-dependent fashion. Consistent with these results, we observed that human cancer samples with deficient B12/FA uptake demonstrated higher transcription of AhR target genes and lower transcription of pathways implicated in birth defects. In contrast, there was no significant difference observed between samples with mutated and intact 1C cycle proteins. Thus, we propose a model in which B12 and FA blunt the effect of natural AhR agonists at baseline to prevent the symptoms that arise with AhR overactivation.


Immunological evaluation of the entirely carbohydrate-based Thomsen-Friedenreich - PS B conjugate.
PS B, a naturally occurring CD4(+) T-cell simulating zwitterionic polysaccharide from Bacteroides fragilis ATCC 25285/NCTC 9343, was conjugated with aminooxy Thomsen Friedenreich (TF or T) [α-d-Gal-(1,3)-β-d-GalNAc-ONH2] tumor antigen. Immunization in Jax C57BL/6, followed by ELISA revealed IgM and IgG antibody TF specificity. FACS data noted preferential binding to TF-laced MCF-7 cells but not to HCT-116 cells.


Dissociation-recombination of sunflower seed acid phosphatase.
Formal genetic studies of sunflower (Helianthus annuus) seed acid phosphatase (ACP, E.C. 188.8.131.52) had suggested that the functional enzyme consists of two polypeptide subunits. The dimeric quaternary structure was demonstrated by dissociation-recombination procedures. Dissociation of electrophoretically distinct homodimers was effected upon freezing of extracts in a pH 8-9 buffer containing 1 M NaCl and 0.1 M 2-mercaptoethanol. Reassociation, as indicated by the formation of the hybrid isozyme, occurred during 12 hr dialysis against a pH 7.0 buffer.


Charge and salt-driven reentrant order-disorder and gas-solid transitions in charged colloids.
Monte Carlo simulations have been performed for aqueous charged colloidal suspensions as a function of effective charge density (sigma) on the particles and salt concentration C(s). We vary the effective charge density in our simulations over a range where a reentrant solid-liquid transition in suspensions of silica and polymer latex particles has been reported by Yamanaka et al. (Phys. Rev. Lett. 80 (1998) 5806). We show that at low ionic strengths a homogeneous liquid-like ordered suspension undergoes crystallization upon increasing sigma. Further increase in sigma resulted once again in a disordered state, which is in agreement with experimental observations. In addition to this reentrant order-disorder transition, we observe an inhomogeneous-to-homogeneous transition in our simulations when salt is added to the disordered inhomogeneous state. This inhomogeneous-to-homogeneous disordered transition is analogous to the solid-gas transition of atomic systems and has not yet been observed in charged colloids. The reported experimental observations on charged colloidal suspensions are discussed in the light of present simulation results.


Membrane interactions in nerve myelin: II. Determination of surface charge from biochemical data.
In our accompanying paper (Inouye and Kirschner, 1988) we calculated the surface charge density at the extracellular surfaces in peripheral and central nervous system (PNS; CNS) myelins from observations on the dependency of the width of the extracellular space on pH and ionic strength. Here, we have determined the surface charge density of the membrane surfaces in myelin from its chemical composition and the localization of some of its molecular components. We then analyzed the attractive and repulsive forces between the apposed surfaces and calculated equilibrium periods for comparison with the measured values. The biochemical model accounts for the observed isoelectric range of the myelin period and, with the surface charge reduced (possibly by divalent cation binding or a space charge approximation), the model also accounts for the dependency of period on pH above the isoelectric range. At the extracellular (and cytoplasmic) surfaces the contribution of lipid (with pI approximately 2) to the net surface charge is about the same in both PNS and CNS myelin, whereas the contribution of protein depends on which ones are exposed at the two surfaces. The protein conformation and localization modulate the surface charge of the lipid, resulting in positively-charged cytoplasmic surfaces (pI approximately 9) and negatively-charged extracellular surfaces (pI approximately 2-4). The net negative charge at the extracellular surface is due in CNS myelin to lipid, and in PNS myelin to both lipid and (PO) glycoprotein. The net positive charge at the cytoplasmic surface is due in CNS myelin mostly to basic protein, and in PNS myelin to PO glycoprotein and basic protein. The invariance of the cytoplasmic packing may be due to specific short-range interactions. Our models demonstrate how the particular myelin proteins and their localization and conformation can account for the differences in inter-membrane interactions in CNS and PNS myelins.


Insulin stimulates incorporation of 32Pi into nuclear lamins A and C in quiescent BHK-21 cells.
The in vivo effect of insulin upon the incorporation of 32Pi into nuclear proteins was investigated in quiescent baby hamster kidney fibroblasts (BHK-21). Insulin has previously been shown to be mitogenic in these cells (Richman, R. A., Johnson, R. A., and Friedman, D. L. (1981) Proc. Soc. Exp. Biol. Med. 168, 196-203). Incorporation into two proteins (Mr = 62,000 and 72,000) in the 0.4 M salt-resistant nuclear fraction was enhanced 2-6-fold by insulin. The effect of insulin (20 nM) was observable within 5 min of treatment, reached a maximum at 15 min, and continued for at least 90 min. The half-maximal effect of insulin was obtained at a concentration of approximately 1 nM. Analysis of nuclear matrix preparations indicated that the two insulin-sensitive proteins were prominent nuclear matrix proteins and suggested that they were lamins A and C. This was confirmed by immunostaining with lamin antibodies and by two-dimensional electrophoresis. These studies indicate that insulin rapidly stimulates the incorporation of phosphate into nuclear lamins A and C in quiescent BHK-21 fibroblasts.


Older people with severe loneliness have an atrophied thalamus, hippocampus, and entorhinal cortex.
Loneliness has been shown to increase the risk of dementia. However, it is unclear why greater loneliness is associated with greater susceptibility to dementia. Herein, we aimed to examine the morphological characteristics of the brain associated with loneliness in older people concerned about cognitive dysfunction. In this retrospective study, 110 participants (80 with amnestic mild cognitive impairment, and 30 cognitively healthy individuals) were included. Participants were assessed using the revised University of California at Los Angeles (UCLA) loneliness scale and had undergone magnetic resonance imaging. Spearman correlation analysis and Mann-Whitney U tests were used to examine the clinical factors associated with loneliness. Multiple regression was performed to examine the relationship between the revised UCLA loneliness scale score and regional gray matter (GM) volume on voxel-based morphometry. The revised UCLA loneliness scale scores were not significantly correlated with age, sex, or mini-mental state examination (MMSE) scores. Multiple regression using age, sex, MMSE score, and total brain volume as covariates showed negative correlations of the revised UCLA loneliness scale scores with the grey matter volume in regions centered on the bilateral thalamus, left hippocampus and left parahippocampal gyrus, and left entorhinal area. Subjective loneliness was associated with decreased GM volume in the bilateral thalamus, left hippocampus, and left entorhinal cortex of the brain in the older people, thereby providing a morphological basis for the increased risk of dementia associated with greater loneliness.


Epidemiology, Risk Factors, and Clinical Outcomes of Bloodstream Infection due to Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in Hematologic Malignancy: A Retrospective Study from Central South China.
Objective: To determine the epidemiology, risk factors, and prognosis of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections (BSIs) among hematology malignancy (HM) patients in China. Method: From January 2010 to June 2018, we retrospectively collected and analyzed the 449 HM patients with E. coli or K. pneumoniae BSIs from three leading hospitals in Hunan Province, China. Results: Two hundred four (45.4%) patients harbored ESBL-producing bacteremia. The proportion of ESBL-producing bacteremia increased significantly with the growth of the year, with a ratio of 34.47% in 2010-2014 to 54.7% in 2015-2018. Comparing with non-ESBL groups in HM patients, central venous catheter (odds ratio [OR] 1.717, p = 0.009), previous antibiotic exposure (OR 1.559, p = 0.035), and E. coli (OR 2.561, p ≤ 0.001) among ESBL groups were independent risk factors. No significant differences in 30-day mortality were tested in patients with BSI caused by ESBL-producing or non-ESBL-producing E. coli and K. pneumoniae (17.1% vs. 16.7%; p = 0. 893). The proportion of carbapenem used within 72 hours after the onset of bacteremia in two groups was high, which was routinely used as "last-resort drugs" in Gram-negative bacterial infections. Risk factors associated with 30-day mortality in HM patients with E. coli or K. pneumoniae bacteremia were myelodysplastic syndrome, incomplete remission of the disease, Multinational Association of Supportive Care in Cancer score <21, Pitt bacteremia score ≥4, Charlson comorbidity score >3, catheter insertion, use of vasopressors, and inappropriate antibiotics within 72 hours of BSI onset. Conclusions: The results of this study may provide some references for the whole process management of HM patients with BSIs.


Correction to: Long-term results achieved by guideline-based stage-dependent management of anal cancer in a non-HIV population.
The authors of the article mentioned above found out errors on the Table 4 concerning the number and survival rates of patients with incomplete radiotherapy.


The art of measuring steroids: Principles and practice of current hormonal steroid analysis.
Steroids are small and highly important structural or signalling molecules in living organisms and their metabolism is complex. Due to the multiplicity of enzymes involved there are many different steroid related disorders. E.g., an individual enzyme defect is rather rare but can share various clinical symptoms and can thus be hardly diagnosed clinically. Therefore, reliable hormonal determination still presents the most reasonable initial diagnostic approach and helps to avoid uncritical and expensive attempts at molecular diagnostic testing. It also presents a backbone of monitoring these complex patients. In science, reliable hormone measurement is indispensable for the elucidation of new mechanisms of steroid hormone actions. Steroid analytics is highly challenging and should never be considered trivial. Most common methods for steroid determination comprise traditionally immunoassay, or more recently, mass spectrometry based methods. It is absolutely necessary that clinicians and scientists know the methods they are applying by heart. With the introduction of automated direct assays, a loss of quality could be observed over the last two decades in the field of steroid immunoassays. This review wants to meet the need for profound information and orientation in the field of steroid analysis. The pros and cons of the most important methods, such as immunoassays and mass spectrometry based methods will be discussed. The focus of the latter will lie on gas chromatography-mass spectrometry (GC-MS) as well as liquid chromatography-mass spectrometry (LC-MS). Selected analytical applications from our Deutsche Forschungsgemeinschaft Research Group FOR 1369 "Sulfated Steroids in Reproduction" will illustrate the contents. In brief, immunoassays have for long presented the traditional technique for steroid analysis. They are easy to set up. Only one analyte can be measured per immunoassay. Specificity problems can arise and caution has to be exerted especially regarding direct assays lacking purification steps. Mass spectrometry based methods provide structural information on the analyte and thus higher specificity. In combination with chromatographic techniques, they permit the simultaneous determination of a multitude of analytes. Highest specificity can be obtained using GC-MS, a sophisticated but most powerful tool for characterizing steroid metabolomes. LC-MS is a true high throughput technique and highly suited for detecting complex steroids. GC-MS and LC-MS are not competing but complementary techniques. Since reliable steroid determination requires extremely high expertise in the field of analytics as well as steroid biochemistry, it is recommended that collaborations and networking with highly specialized centers of expertise are developed.


A new radiopharmaceutical: 99mTc DMP for renal scanning.
99mTc-Dimercaptopropionic acid (DMP), a new renal scanning agent was synthesized, and the optimum preparative conditions and stability of this compound were determined. It was demonstrated that scans performed with this agent in rats showed highly selective renal images which may be of promise in future clinical use. The relationships between chemical structure and renal affinity are discussed based on the present results.


Antinociceptive effects of supraspinal rat cart (55-102) peptide in mice.
We investigated the effects of rat cocaine- and amphetamine-regulated transcript CART (55-102) after i.c.v. administration in mouse models of acute and persistent pain. CART was not active in the tail-flick or PPQ tests. It increased the latency to paw licking in the hot-plate test but only at doses that impaired motor function. CART produces antinociception in the formalin test in both phases. Our results suggest that CART is involved in supraspinal pain transmission.


Investigating science teachers' intention to adopt virtual reality through the integration of diffusion of innovation theory and theory of planned behaviour: the moderating role of perceived skills readiness.
This study contributes to the extant literature on instructional technology by investigating the relationships between the social and personal factors and behavioral intention to use virtual reality. Moreover, the current study examined the links between perceived characteristics of virtual reality and attitude and the moderating role that can be played by perceived skills readiness between those links. Inspired by the Theory of Planned Behaviour and Diffusion of Innovation Theory, a set of hypotheses was formed to test the proposed relationships using structural equation modeling partial least square to a sample of 171 science teachers in Oman. The results showed that attitude, social norms and perceived behavioral control can predict behavioral Intention to use virtual reality with attitude as the strongest predictor. Furthermore, the results indicated that relative advantage could predict attitude towards using virtual reality while compatibility and observability cannot. Finally, perceived skills readiness can strengthen the relationship between the perceived characteristics of virtual reality applications (relative advantage, compatibility and observability) and attitude towards using the virtual reality in the science classroom. Thus, this study highlights the importance of focussing on science teachers' skills readiness to use virtual reality so that they can use it confidently. Implications and future research studies are discussed.


[Clinical and electromyographic characteristics of syndromes of pathologic muscular fatigue of the myasthenic type].
On the basis of the follow-up study of more than 2000 patients with different forms of pathological muscular fatiguability of the myasthenic type, the authors emphasize the heterogeneity of this group of patients. The detailed study of clinical and electromyographic picture permitted them to distinguish the following clinical forms; myasthenia, myasthenic syndrome in terminal polyneuropathy, the myastheniapolymyositis complex, myasthenic syndrome of Lambert--Etone type.


Integrated decision making: definitions for a new discipline.
The birth and early growth of a new discipline from the union of evidence-based medicine (EBM) and the theoretical foundations of human psychology and behaviour has led to a plethora of new terms to define and redefine a paradigm shift in clinical decision making. This paper provides a short glossary of (1) terms to describe the practitioner-patient relationship in decision making and (2) terms describing some of the tools for facilitating evidence-based decision making. In addition, it is proposed that a more acceptable name for this discipline may be 'integrated decision making' (IDM). A case is argued for the fact that this term better addresses many of the concerns raised by practitioners and consumers about barriers to the integration of evidence and patient preferences in clinical practice and the changing nature of the practitioner-patient relationship in healthcare today.


Orange juice substantially reduces the bioavailability of the beta-adrenergic-blocking agent celiprolol.
Grapefruit juice was recently found to decrease plasma concentrations of the beta-adrenergic receptor-blocking agent celiprolol. Our objective was to investigate the effect of orange juice on the pharmacokinetics of celiprolol in healthy subjects. In a randomized crossover study with 2 phases and a washout of 2 weeks, 10 healthy volunteers ingested either 200 mL normal-strength orange juice or water 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of 200 mL orange juice or water, each subject ingested 100 mg celiprolol with either 200 mL orange juice or water. In addition, 200 mL orange juice or water was ingested at 4, 10, 22, and 27 hours after celiprolol intake. The concentrations of celiprolol in plasma and its excretion into urine were measured up to 33 hours after its dosing. Systolic and diastolic blood pressures and heart rate were recorded up to 10 hours. Orange juice reduced the mean peak plasma concentration of celiprolol by 89% (P <.01) and the mean area under the plasma celiprolol concentration-time curve by 83% (P <.01). The time to peak concentration of celiprolol increased from 4 to 6 hours (P <.05), and the half-life was prolonged from 4.6 to 10.8 hours (P =.05) after ingestion of orange juice. Orange juice reduced the urinary excretion of celiprolol by 77% (P <.01). No significant differences were observed in the hemodynamic variables between the phases. Orange juice substantially reduces the bioavailability of celiprolol, but the mechanism of this interaction remains to be resolved. For example, modulation of intestinal pH and of function of transporters implicated in the absorption of celiprolol may be involved. Because of the great extent of the orange juice-celiprolol interaction and a wide use of orange juice, this interaction is likely to have clinical importance in some patients, although hemodynamic consequences were not seen in young healthy subjects.


New insight into ZnO@ZIFs composite: an efficient photocatalyst with boosted light response ability and stability for CO2 reduction.
One of the main causes of climate change and energy exhaustion is the excessive use of fossil fuels. Photocatalytic carbon dioxide (CO2) reduction technology uses inexhaustible sunlight to directly convert CO2 into value-added chemicals or fuels not only solving the problem of greenhouse effect but also alleviating the shortage of fossil energy. In this work, a well-integrated photocatalyst is synthesized through growing zeolitic imidazolate frameworks (ZIFs) with different metal nodes on ZnO nanofiber (NFs) for CO2 reduction. One-dimensional (1D) ZnO NFs have better CO2 conversion efficiency due to the high surface-to-volume ratio and low light reflectivity. 1D nanomaterials with superior aspect ratios can be assembled into free-standing flexible membranes. In addition, it has been found that ZIFs nanomaterials with bimetallic nodes not only have better CO2 reduction capabilities but also exhibit superior thermal and water stability. The photocatalytic CO2 conversion efficiency and selectivity of ZnO@ZCZIF are shown to be significantly enhanced which can be attribute to the strong CO2 adsorption/activation, efficient light capture, excellent electron-hole pair separation efficiency, and specific metal Lewis sites. This work provides insights into the rational construction of well-integrated composite materials to improve the photocatalytic carbon dioxide reduction performance.


Heat-resistant, extended-spectrum β-lactamase-producing Klebsiella pneumoniae in endoscope-mediated outbreak.
We describe an outbreak with an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain in an intensive care unit in a secondary care hospital in Norway. The outbreak source was a fibreoptic intubation endoscope in which the outbreak strain survived despite chemothermal disinfection in a decontaminator designated for such use. The genetic marker clpK, which increases microbial heat resistance, has previously been described in K. pneumoniae outbreak strains. To investigate the role of clpK in biofilm formation and heat-shock stability in the outbreak strain. The outbreak investigation was done by review of clinical records, screening of patients and culture from intubation endoscopes and bronchoscopes. Amplified fragment length polymorphism was used to identify the outbreak strain. clpK detection was performed by polymerase chain reaction, followed by mutant construction and heat-shock assays. Five patients and one intubation endoscope contained K. pneumoniae with the same amplified fragment length polymorphism pattern. The outbreak strain contained the clpK genetic marker, which rendered the strain its increased heat resistance. The survival rate of the strain grown as biofilm following heat treatment was also strongly dependent on clpK. Although clpK has been associated with clinical isolates of K. pneumoniae in earlier outbreaks, this is the first time that a ClpK-producing strain has been isolated from an environmental outbreak source. Heat resistance of certain K. pneumoniae strains may facilitate survival in biofilms on medical equipment and hence increase the potential of those strains to persist and disperse in the hospital environment.


Sensitive determination of As (III) and As (V) by magnetic solid phase extraction with Fe@polyethyleneimine in combination with hydride generation atomic fluorescence spectrometry.
The magnetic nanomaterial Fe@polyethyleneimine (Fe@PEI) was successfully synthesized and used as an effective adsorbent material for magnetic solid phase extraction(MSPE) of As(III) and As(V) from water samples. Fe@SiO2 nanoparticles were prepared by one pot synthetic method using a borohydride reduction method, then modified with (3-chloropropyl)trimethoxysilane to obtain Fe@SiO2-Cl by chloropropylation, which was reacted with PEI to achieve Fe@polyethyleneimine (Fe@PEI). The microstructure and morphology of Fe@PEI were characterized by transmission electron microscoscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). The experimental results showed that Fe@PEI demonstrated excellent adsorption for As(III) and As(V). Based on this fact, the determination method for these two arsenic species earned good limits of detection (LODs) of 0.002μgL(-1) and wide calibration curves in the concentration range from 0.008 to 0.2μgL(-1). The precisions of As (III) and As (V)were 1.95% and 2.55% (RSD, n=6), respectively. The proposed method was validated with real samples and the spiked recoveries were in the range of 82.7-98.3% and the accuracies were in the range of 2-13.3%. The results demonstrated that the developed MSPE method had good advantages such as simplicity, rapid separation, low cost, easy to reuse and high-quality analytical performances, which made it attractive for rapid and efficient extraction of inorganic arsenic species in the environmental water samples.


Diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy.
Breast cancer is a leading cause of cancer-related death worldwide, and chemoresistance often leads to poor patient outcomes. In this study, we investigated the anticancer activity of synthetic diphenyl disulfide (DPDS) in breast cancer cell lines. DPDS inhibited cellular proliferation and viability in a dose-dependent manner and reduced colony formation, an index of clonogenicity. Annexin-V and 7-AAD double staining showed that DPDS could induce the apoptosis of breast cancer cells. Western blotting of the expression of Bax p21 and its cleaved form p18 suggested the activation of p18 Bax-induced apoptosis. Furthermore, the increased expression of the autophagy marker LC3B-II indicated autophagic lysosome accumulation induced by DPDS. Our findings suggest that DPDS has potential as a candidate for treating breast cancer, and further modifications and optimizations are warranted.


Interaction of factors associated with cancer of the nasopharynx.
A retrospective study of nasopharyngeal carcinoma (NPC) revealed that smoking, working under poor ventilation, use of nasal balms or oil for nasal and throat troubles, use of herbal drugs, and anti-EBV antibody titer were found statistically associated. The dural interactions of these factors to the risk of NPC were presented. Except in work conditions with poor ventilation and when herbal drugs are used, all the combinations were synergistic. The synergistic actions were especially remarkable with smoking and other factors. The possible etiological mechanisms of NPC are discussed.


Research participants' perceptions and views on consent for biobank research: a review of empirical data and ethical analysis.
Appropriate information and consent has been one of the most intensely discussed topics within the context of biobank research. In parallel to the normative debate, many socio-empirical studies have been conducted to gather experiences, preferences and views of patients, healthy research participants and further stakeholders. However, there is scarcity of literature which connects the normative debate about justifications for different consent models with findings gained in empirical research. In this paper we discuss findings of a limited review of socio-empirical research on patients' and healthy research participants' experiences and views regarding consent to biobank research in light of ethical principles for appropriate information and consent. Review question: Which empirical data are available on research participants' perceptions and views regarding information and elicitation of consent for biobank research? Search of articles published till March 1st 2014 in Pubmed. Review of abstracts and potentially relevant full text articles by two authors independently. As categories for content analysis we defined (i) understanding or recall of information, (ii) preferences regarding information or consent, and (iii) research participants' concerns. The search in Pubmed yielded 337 abstracts of which 10 articles were included in this study. Approaches to information and consent varied considerably across the selected studies. The majority of research participants opted for some version of limited consent when being informed about such possibility. Among the factors influencing the type of preferred consent were information about sponsoring of biobank research by pharmaceutical industry and participants' trade-off between privacy and perceived utility. Studies investigating research participants' understanding and recall regarding the consent procedure indicated considerable lack of both aspects. Research participants' perceptions of benefits and harms differ across those studies. The knowledge, perceptions and views of research participants who have undergone a consent procedure within the context of biobank research raise several questions on the issue of how to inform and elicit consent in an ethically acceptable way. In our empirical-ethical analysis we develop suggestions on how the practice of eliciting consent in the biobank context should be improved.


Neurodevelopmental outcome in 7-year-old children is not affected by exercise during pregnancy: follow up of a multicentre randomised controlled trial.
To investigate whether regular moderate intensity exercise during pregnancy had adverse effect on neurodevelopment of offspring at 7 years of age. Follow up of a multicentre randomised controlled trial. St Olavs Hospital, Trondheim University Hospital and Stavanger University Hospital, Norway (2007-09). Women randomised to follow a 12-week structured exercise protocol or standard antenatal care during pregnancy. At 7 years of age, neurodevelopmental outcome was assessed by the parent questionnaire Five-To-Fifteen (FTF), including motor skills, executive functions, perception, memory, language, social skills and possible emotional/behavioural problems. Continuous and dichotomised (cut-off 90th centile) FTF scores. A total of 855 women were randomised to exercise (n = 429) or standard antenatal care (n = 426) during pregnancy. At follow up, 164 (38.2%) children born to mothers in the intervention group and 115 (27.0%) children born to mothers in the control group participated. We found no group differences in FTF scores or in the proportion of children with scores ≥90th centile. Stratified analyses by sex, subgroup analyses of women who adhered to the exercise protocol or sensitivity analyses excluding preterm children and/or children who had been admitted to the neonatal intensive care unit did not change the results. In the present randomised controlled trial follow-up study, regular moderate intensity exercise during pregnancy did not have adverse effect on neurodevelopment of offspring at 7 years of age. Moderate intensity exercise during pregnancy had no adverse effect on neurodevelopment of offspring at 7 years of age.


Proton beam output measurement with an extrapolation chamber.
A variable air-volume, parallel-plate extrapolation chamber forming an integral part of a polystyrene phantom was used in measurement of dose rate in a 250 MeV clinical proton beam. The sensitive air-volume of the extrapolation chamber is controlled through the movement of the chamber piston by means of a micrometer mounted on the phantom body. The relative displacement of the piston is monitored by a calibrated mechanical distance travel indicator. The proton beam dose rate determined with the uncalibrated extrapolation chamber was 5% lower than the dose rate determined with a calibrated Farmer-type thimble chamber at the same depth in the polystyrene phantom. Despite the current 5% discrepancy, uncalibrated extrapolation chambers may offer a simple and practical alternative to current techniques used in output measurements of proton beam machines.


Environmental chemicals as thyroid hormone analogues: new studies indicate that thyroid hormone receptors are targets of industrial chemicals?
Thyroid hormone (TH) is essential for normal brain development, but the specific actions of TH differ across developmental time and brain region. These actions of TH are mediated largely by a combination of thyroid hormone receptor (TR) isoforms that exhibit specific temporal and spatial patterns of expression during animal and human brain development. In addition, TR action is influenced by different co-factors, proteins that directly link the TR protein to functional changes in gene expression. Several recent studies now show that TRs may be unintended targets of chemicals manufactured for industrial purposes, and to which humans and wildlife are routinely exposed. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and bisphenol-A (BPA), and specific halogenated derivatives and metabolites of these compounds, have been shown to bind to TRs and perhaps have selective effects on TR functions. A number of common chemicals including polybrominated biphenyls (PBBs) and phthalates may also exert such effects. Considering the importance of TH in brain development, it will be important to pursue the possibilities that these chemicals - or interactions among chemical classes - are affecting children's health by influencing TH signaling in the developing brain.


The density-dependency of dark- and low-background radiation effects on water and water solution properties.
The effects of dark -(Ev=0 lux) and low-background radiation (BGR), where R<1μRongen/h, on physicochemical properties (specific electrical conductivity, heat fusion, hydrogen peroxide (H2O2), and oxygen contents) of distilled water (DW) and physiological solution (PS) at 4°C and 18°C were studied. The incubation of DW and PS samples in dark and in low BGR (under dark) medium at 4°C and 18°C brings to changes of their physicochemical properties compared with DW and PS samples incubated in light and normal BGR condition (Ev=500-550 lux and R=17 μRoentgen/h). The observed changes of DW and PS properties depended on their initial temperature, density and ionic composition. It is suggested that water molecules dissociation and ions hydration are sensitive to illumination and BGR. Therefore, the cell-bathing medium can be considered as a messenger through which direct and non direct (by modulating of others factors-induced effects) influences of illumination and BGR on cell metabolism are realized.


Co-ordination between localized wound-induced Ca2+ signals and pre-wound serum signals is required for proliferation after mechanical injury.
The signals which initiate proliferation of endothelial cells after injury are important for selective blood vessel growth during wound healing or tumour growth. Upon mechanically wounding quiescent cells, a transient [Ca2+]i increase was induced in cells at the wound edge. These same cells proliferated 18-24 h post wounding, as measured by bromodeoxyuridine incorporation. The localized Ca2+ signal was required specifically during wounding since blocking Ca2+ influx reduced proliferation by 40-50%. Proliferation also required serum since starvation reduced proliferation by 80%. Serum-starved cells proliferated if briefly primed with serum prior to wounding. The signals derived from serum and [Ca2+]i combined at least additively to induce proliferation. Therefore, serum priming followed by a single, transient Ca2+ signal induced by mechanical injury must occur in a temporally and spatially regulated manner for normal proliferation. Co-ordination between signalling cascades induced by growth factors and release from contact inhibition might be obligatory for localized re-endothelialization after injury.


Hollows on Mercury: MESSENGER evidence for geologically recent volatile-related activity.
High-resolution images of Mercury's surface from orbit reveal that many bright deposits within impact craters exhibit fresh-appearing, irregular, shallow, rimless depressions. The depressions, or hollows, range from tens of meters to a few kilometers across, and many have high-reflectance interiors and halos. The host rocks, which are associated with crater central peaks, peak rings, floors, and walls, are interpreted to have been excavated from depth by the crater-forming process. The most likely formation mechanisms for the hollows involve recent loss of volatiles through some combination of sublimation, space weathering, outgassing, or pyroclastic volcanism. These features support the inference that Mercury's interior contains higher abundances of volatile materials than predicted by most scenarios for the formation of the solar system's innermost planet.


Serum Fetuin-A and Pentraxin3 in hemodialysis and renal transplant patients.
The aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients. Serum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods. In the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09-20.36) ng/mL vs. 1.65(0.24-7.89) ng/mL, p ≤ 0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75-81.48) ng/mL vs. 38.76(22.26-89.07) ng/mL, p=0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1-8.50) mg/L vs. 1.1(0.1-7.9) mg/L, p=0.003]. Although our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future.


Polyethylenglycol-co-poly-D,L-lactide copolymer based microspheres: preparation, characterization and delivery of a model protein.
To prepare and characterize polyethylenglycol-co-poly-D,L-lactide (PEG-D,L-PLA) multiblock copolymer microspheres containing ovalbumin. Microsphere batches made of Poly-D,L-lactide (PLA) homopolymers were prepared in order to evaluate how the presence of PEG segments into PEG-D,L-PLA copolymer could affect the behaviour of microspheres as carrier of protein drugs. The PEG-D,L-PLA and PLA microspheres, loaded with the model protein ovalbumin, were prepared using double emulsion solvent evaporation method. The effect of PEG segments in the microparticles matrix, on the morphology, size distribution, encapsulation efficiency and release behaviour was studied. According to the results, PEG-D,L-PLA microspheres were more hydrophilic than PLA microparticles and with lower glass transition temperature. The surface of PEG-D,L-PLA microspheres was not as smooth as that of PLA microparticles, the mean diameter of PEG-D,L-PLA microparticles was bigger than that of PLA microspheres. Protein release from the microspheres was affected by the morphological structure of PEG-D,L-PLA microspheres and properties of PEG-D,L-PLA copolymer. This study suggests that PEG-D,L-PLA multiblock copolymer may be used as carrier in protein delivery systems for different purposes.


Human cytomegalovirus infection and antiviral immunity in septic patients without canonical immunosuppression.
The human cytomegalovirus (HCMV) is a relevant pathogen in patients with immunosuppressive therapy; however, reactivation and subsequent recurrence occurs also in individuals without canonical immunosuppression as e.g., in patients with septic shock. Analyzing the impact of NK- and T-cell immunity on the natural course of HCMV infection in patients with septic shock, it became clear that the presence of HCMV reactive T-helper cells did not prevent the development of reactivation but, the control of active infection was achieved mostly by specific T-cells. NK-cells seemed to be dispensable for clearance of active infection in this patient group with long-lasting NK-cell anergy.


"This is a Titanic song": the effect of familiarity on children's learning affective meaning in music.
Usage-based theories of language acquisition are thought to rely on domain-general learning mechanisms, such as mastering familiar routines by rote before generalizing to novel unfamiliar instances. If so, then the role of familiarity should extend to non-linguistic domains, like music. The purpose of the present study was to test the role of familiarity in children's learning of affective meaning of music. Music carries an affective meaning that is relayed through its elements, such as mode, rhythm, and tempo. The previous research has found differences between children and adults in their understanding of music's affective meaning, suggesting that this meaning is learned. We predicted that children would initially learn the affective meaning of familiar musical pieces before generalizing to unfamiliar pieces. Children between 3 and 5 years of age heard 16 musical segments, one for each emotion (i.e., anger, sadness, and happiness), and their accuracy in pairing music-emotion was measured. For younger children, their familiarity with the piece was positively associated with their accuracy. These results suggest that familiarity plays a role in learning affective meaning in music, providing support for the claim that this learning mechanism is domain-general.


Complete Genome Sequence of Stenotrophomonas sp. Strain WZN-1, Which Is Capable of Degrading Polybrominated Diphenyl Ethers.
Stenotrophomonas sp. strain WZN-1, isolated from an e-waste recycling area in Tianjin, China, is capable of degrading polybrominated diphenyl ethers (PBDEs). The complete genome of strain WZN-1 consists of 4,512,703 bp. This genome information will provide important information about the biodegradation pathways and mechanisms of PBDEs.


Ecophysiology of constitutive and facultative CAM photosynthesis.
In plants exhibiting crassulacean acid metabolism (CAM), CAM photosynthesis almost always occurs together with C3 photosynthesis, and occasionally with C4 photosynthesis. Depending on species, ontogeny, and environment, CAM input to total carbon gain can vary from values of <1% to 100%. The wide range of CAM phenotypes between and within species is a fascinating example of functional diversity and plasticity, but poses a significant challenge when attempting to define CAM. CO2 gas exchange experiments designed for this review illustrate key patterns of CAM expression and highlight distinguishing features of constitutive and facultative CAM. Furthermore, they help to address frequently recurring questions on CAM terminology. The functional and evolutionary significance of contrasting CAM phenotypes and of intermediate states between extremes is discussed. Results from a study on nocturnal malate accumulation in 50 species of Aizoaceae exposed to drought and salinity stress suggest that facultative CAM is more widespread amongst vascular plants than previously thought.


Female-specific neuroprotection against transient brain ischemia observed in mice devoid of prion protein is abolished by ectopic expression of prion protein-like protein.
This study was designed to examine the function of cellular prion protein and prion protein-like protein/Doppel, in transient ischemia-related neuronal death in the hippocampus. Two different lines of mice devoid of cellular prion protein, Zrch I Prnp(0/0) and Ngsk Prnp(0/0), were used. The former lacks cellular prion protein whereas the latter ectopically expresses prion protein-like protein/Doppel in the brain in the absence of cellular prion protein. Mice were subjected to 10 min-occlusion of the bilateral common carotid arteries with recovery for 14 days. Less than 10% of the pyramidal neurons in the CA1 subfield were degenerated in male and female wild-type mice. In contrast, more than half of the neurons were lost in male Zrch I Prnp(0/0) and Ngsk Prnp(0/0) mice. Such severe neuronal loss was also observed in female Ngsk Prnp(0/0) mice. However, female Zrch I Prnp(0/0) mice showed mild neuronal loss similar to wild-type mice. Flunarizine, a T- and L-type Ca(2+)-channel antagonist, significantly reduced the neuronal loss in female but not in male Ngsk Prnp(0/0) mice. These results indicate that loss of cellular prion protein renders hippocampal neurons susceptible to ischemic insult specifically in male but not female mice and the ectopic expression of prion protein-like protein/Doppel aggravates the ischemic neuronal death in female prion protein-null mice probably via overloading of Ca(2+)-dependent signaling.


Application of low-level laser therapy for noninvasive body contouring.
Low-level laser therapy (LLLT) is a noninvasive treatment for a wide-assortment of medical ailments. A recent application is for noninvasive body slimming. A Level 1 clinical study was completed and recorded a significant reduction in circumferential measurements across waist, hips, and thighs compared to placebo subjects. Questions remain unanswered to whether the result observed was based upon simple fluid redistribution. The purpose of this retrospective study was to evaluate the efficacy of LLLT for noninvasive body slimming and determine if the loss was attributable to fluid or fat relocation. Data from 689 participants were obtained to evaluate the circumferential reduction demonstrated across the treatment site of the waist, hips, and thighs as well as nontreated systemic regions. Patient data were not pre-selected; all reports provided by clinics using LLLT for body contouring were used to evaluate the efficacy of this treatment. Participants received a total of six LLLT treatments across 2-weeks having baseline and post-procedure circumferential measurements recorded. Measurement sites included waist, hips, thighs, arms, knees, neck, and chest. The mean circumferential reduction reported for the waist, hips, and thighs 1 week after the treatment regimen was 3.27 in. (P < 0.0001). Furthermore, participants demonstrated an overall mean reduction of 5.17 in. across all measurement points 5.17 in. (P < 0.0001). Each anatomical region measured exhibited a significant circumferential reduction. These data reveal that the circumferential reduction exhibited following LLLT is not attributable to fluid or fat relocation as all measurement points, including nontreated regions, reported an inch loss.


MiR-1908 promotes scar formation post-burn wound healing by suppressing Ski-mediated inflammation and fibroblast proliferation.
The cell biological basis for scar formation is mainly via excessive fibroblast proliferation accompanied by hypernomic Col I accumulation and inflammation. The role of miR-1908 in scar formation has not been investigated. In this study, we found that miR-1908 expression was inversely associated with the scar suppressor Ski in normal, burn-wounded, healing and scar dermal tissues in humans. Bioinformatics and luciferase reporter gene assays confirmed that miR-1908 targeted the 3'UTR region of Ski mRNA and suppressed Ski expression. Next, human scar epidermal fibroblasts were isolated and the miR-1908 oligonucleotide mimic and inhibitor were respectively transfected into the cells. Western blot analysis proved that Ski expression was sharply reduced by the miR-1908 mimic. MTT and Cell Counting Kit-8 analyses showed that miR-1908 mimic transfection promoted cell proliferation. Simultaneously, data on real-time qPCR analysis indicated that expression of the fibrotic master gene TGF-β1, Ski-suppressing gene Meox2, Col I and proinflammatory markers IL-1α and TNF-α, were all significantly upregulated. In contrast, the miR-1908 inhibitor had a completely opposite effect on cell proliferation and gene expression. The mimic and inhibitor were locally injected into rats with abdominal burn-wounded scars during a 180-day, post-healing experiment. The miR-1908 mimic injection significantly reduced Ski expression, as well as the area, volume and fibrosis of scars in vivo. And, in contrast, the miR-1908 inhibitor injection had an opposite effect to that of the miR-1908 mimic injection. In conclusion, miR-1908 had a positive role in scar formation by suppressing Ski-mediated inflammation and fibroblast proliferation in vitro and in vivo.


Detection and assessment of infectivity of hepatitis E virus in urine.
Hepatitis E virus (HEV) is known to be excreted in the stool but there has been no report of its presence in urine. This study investigated the presence of HEV RNA and antigen (HEV-Ag) in urine and its possible transmission. Serum and urine samples from patients with chronic or acute HEV infection and HEV infected monkeys were tested for viral and biochemical markers. Liver and kidney biopsies from the infected monkeys were analyzed by histopathology and immunohistochemistry. The infectivity of HEV from urine was assessed by inoculation into monkeys. HEV RNA and HEV-Ag were detected persistently in the urine of a patient with chronic HEV infection. Subsequently, HEV RNA was detected in the urine of three of the eight (37.5%) acute patients, all of whom had detectable HEV-Ag in their urine. HEV RNA and HEV-Ag were also detectable in the urine of HEV infected monkeys. The ratio of HEV-Ag to RNA in the urine of the infected monkeys was significantly higher than in their sera and feces. The parameters of routine urinalysis remained within the normal ranges in the hepatitis E patients and infected monkeys, however, pathological changes and HEV-Ag were observed in the kidneys of the infected monkeys. Furthermore, one of two monkeys became infected with HEV after inoculation with urine from another infected monkey. HEV infection may result in kidney injury and the urine may pose a risk of transmission. HEV-Ag detection in urine may be valuable for diagnosis of ongoing HEV infection.


[Clinical manifestations of Lyme disease in pediatric neurology].
The most important characteristics of Lyme disease in childhood age are presented. Difficulties in diagnostics and the most important possibilities in differential diagnosis are stressed. It is believed that some cases of lyme disease remain unrecognized as the result of poor knowledge about the disease--a not unexpected fact considering that lyme disease is described only in the newest editions of pediatric neurology.


Selectively Depopulating Valley-Polarized Excitons in Monolayer MoS2 by Local Chirality in Single Plasmonic Nanocavity.
Transition metal dichalcogenides, whose valley degrees of freedom are characterized by the degree of circular polarization (DCP) of the photoluminescence, draw broad interests due to their potential applications in information storage and processing. However, this DCP is usually low at room temperature due to the phonon-assisted intervalley scattering, severely degrading the fidelity of the valley-stored signals. Therefore, achieving high DCP at room temperature is vital for valley-encoded nanophotonic devices. In this work, we demonstrate a high DCP of 48.7% at room temperature by embedding monolayer MoS2 into a compact plasmonic nanocavity. Such a high DCP is proven to originate from the prominent chiral Purcell effect owing to the degeneracy-lifted circularly polarized local density of states in the nanocavity. In addition, the DCP can be further manipulated by an in situ plasmon-scanned technique. This highly compact system provides possibilities for developing versatile valley-encoded light-emitting devices at room temperature.


High-performance liquid affinity chromatography of liver plasma membrane proteins.
Plasma membrane proteins from liver were analysed by concanavalin A affinity and immunoaffinity high-performance liquid chromatography. In the method, four peptide bands with apparent molecular weights of 140,000, 120,000, 80,000 and 60,000 could be isolated. In the second method, with two immobilized monoclonal antibodies, two corresponding antigens--the membrane proteins dipeptidyl-peptidase IV and GP 110--could be highly purified from plasma membrane extract with good yield in only one step.


Adaptations of immature trabecular bone to moderate exercise: geometrical, biochemical, and biomechanical correlates.
Strenuous endurance exercise can adversely affect the mechanical integrity of immature bone, but it is unclear whether a more moderate exercise regimen would have a positive effect. Thus, to investigate the response of immature trabecular bone to moderate exercise, we randomly assigned female Sprague-Dawley rats (8 weeks old) to either a basal-control, exercise, or age-matched control group. The basal-control rats were killed at 8 weeks of age, while the other two groups were killed at 18 weeks of age. Between 8 and 18 weeks, one group remained sedentary, while another group was trained progressively on a motor-driven treadmill at a moderate level of intensity. Rat femoral necks (FN) were tested in cantilever bending to failure, and the sixth lumbar vertebral bodies (L6) were compressed to 50% of their initial height. Both tissues were analyzed for calcium, hydroxyproline, and collagen-crosslinking concentrations, and for changes in geometry. The adrenal mass per unit body mass was significantly greater in the exercised group, compared to the age-matched controls. L6 calcium content, compressional stress, and elastic modulus were significantly less in the exercise group as compared to the age-matched control group. Nonreducible collagen crosslinks (hydroxylysylpyridinoline [HP] and lysylpyridinoline [LP]) were significantly greater in the older exercise and age-matched control L6 and FN. In the weightbearing FN--but not L6--the LP concentration of the exercise group was significantly greater than the age-matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Autoregulation in Infants with Neonatal Encephalopathy.
Researchers from Johns Hopkins School of Medicine report a pilot observational study investigating the influence of hemodynamic management in 28 neonates with hypoxic ischemic injury (HIE).


Reverse correlation of Jab1 and Smad4 in PANC-1 cells involved in the pathogenesis of pancreatic cancer.
Steps in the genetic basis of pancreatic cancer (PC) have been recently identified, however, Studies focusing on the relationship between Jab1 and Smad4 in PC are rarely reported. This study was performed to examine the expression patterns and association of Jab1 and Smad4 in PC cells for gaining a further understanding of PC pathogenesis. Human pancreatic cancer cell line PANC-1 cells were infected with retrovirus vector containing GFP, HA-Jab1, siGFP, and siJab1 respectively. The expression of Jab1 and Smad4 in PANC-1 cells was analyzed by Western blot and immunocytochemistry. Subsequently, the effect of overexpression of Jab1 on cell proliferation inhibition mediated by TGF-β was examined with MTT colorimetry. The expression of Smad4 in PANC-1 cells was inhibited after the overexpression of Jab1. Inversely, the expression of Smad4 was increased after the down-regulation of Jab1 silenced by SiRNA. Smad4 expression in PANC-1 cells was negatively correlated with Jab1 expression. In addition, the cell proliferation inhibitory effect induced by TGF-β in PANC-1 cells was attenuated after the overexpression of Jab1. The reverse correlation of Jab1 and Smad4 in PANC-1 cells may be involved in the Pathogenesis of PC. Jab1 can cause degradation of Smad4 via TGF-β signal pathway, consequently contributing to the proliferation of PC cells.


Tuning the electrical transport of type II Weyl semimetal WTe2 nanodevices by Ga+ ion implantation.
Here we introduce lattice defects in WTe2 by Ga+ implantation (GI), and study the effects of defects on the transport properties and electronic structures of the samples. Theoretical calculation shows that Te Frenkel defects is the dominant defect type, and Raman characterization results agree with this. Electrical transport measurements show that, after GI, significant changes are observed in magnetoresistance and Hall resistance. The classical two-band model analysis shows that both electron and hole concentration are significantly reduced. According to the calculated results, ion implantation leads to significant changes in the band structure and the Fermi surface of the WTe2. Our results indicate that defect engineering is an effective route of controlling the electronic properties of WTe2 devices.


Three cases in Japan occurred by natural hazards and lessons for Natech disaster management.
Due to recent climate change, highly-connected society, and the centralization of hazardous materials, Natech is a matter of the growing concern. As Natech disasters occur with low frequency, those in charge of facilities should learn lessons from past cases to prepare for situations in the future in which they may have to respond to a potentially catastrophic event for the first time. This paper describes three Natech cases triggered by the heavy rainfall in Japan in 2018. One resulted in violent explosions, one showed consequences half a year later, and the other managed to avoid a catastrophic situation by preparation based on prior analysis of possible damage. The lessons which can be learnt are as follows: Undertake measures based on the hazardous conditions of materials and possible reactions; Avoid normalcy bias for improved decision-making; Identify slow developing and lagging Natech consequences; Prepare and intensify safeguards to avoid possible damage based on risk analysis; Consider employees' safety in returning to their homes; Collect micro information and aggregate it; Provide current information about the situation to stakeholders; Plan resources required for recovery activities.


Malignant Leydig cell tumour in a Tupaia belangeri: case report and literature review of male genital tumours in non-human primates.
After a short summary of the few reported tumours of the male genital system in non-human primates, a malignant Leydig cell tumour is described in an adult male Tupaia belangeri. The tumour had metastasized in the omentum probably by haematogenous spread enabled by the peculiar perivascular growth pattern of the tumour cells. Its differential diagnosis versus seminomas and Sertoli cell tumours is discussed.


Evaluation of persistent coarctation of aorta after surgery with blood pressure measurement and exercise testing.
In 16 patients with coarctation of the aorta blood pressure in the arms and legs was measured before and after exercise using a treadmill and the Bruce protocol to achieve a standardized level of exercise. Three patients had had no previous operation; 13 had had a previous surgical repair of the coarctation. Three patients were studied both before and after operation. Two of the 13 patients studied postoperatively were found to have significant residual coarctation on the basis of a postexercise arm to leg pressure gradient that had not been appreciated on routine postoperative examination, and one of these patients was found to have residual coarctation after his second operation. One patient not operated on was believed to have mild coarctation of no clinical significance. Eleven of the 13 patients previously operated on (85%) were found to have had a satisfactory repair. A postexercise arm to leg systolic blood pressure gradient of more than 35 mm Hg after repair of coarctation of the aorta is suggested as an indication for recatheterization.


[Surgical management of retrosternal goitre: experience of a Moroccan centre].
This was a retrospective study reviewing 93 cases of retrosternal goitre (RG) operated in our department, with the aim of describing epidemiological and clinical data and discussing the surgical challenges of RG. From January 2004 to December 2012, 35 men and 58 women presenting with RG had surgery. Eighty-nine cases (95.7%) underwent cervicotomy, and a sternotomy was mandatory in 4 cases (4.3%). Laryngoscopy was performed in all cases. A second preoperative laryngoscopy by a senior was mandatory for patients with hoarseness or dyspnea even if the initial laryngeal exam was normal. A cervical mass was noted in 81 cases (87.1%), dyspnea in 17 cases (18.3%), dysphagia in 2 cases (2.1%), hoarseness in 7 cases (7.5%), partial vena cava syndrome in 2 cases and recurrent goitre was noted in 2 cases (2.1%) after previous thyroid resection. Mediastinal extension was on the left side in 47 cases (50.5%), on the right side in 29 cases (31.2%) and bilateral in 17 cases (18.3%). A total thyroidectomy was performed in 86 cases (92.5%) and a unilateral isthmo-lobectomy was performed in 7 cases (7.5%). Mean goitre size was 9.3 cm. Postoperative complications were present in 9 cases (9.7%), 3 cases with hypoparathyroidism (3.2%) and 4 cases (4.3%) of recurrent nerve injury. There was no postoperative death. The histological study objectified 88 cases of multiheteronodular goitre, 4 cases of Basedow thyroid, and 1 case of thyroid carcinoma (papillary carcinoma). Our experience confirms that cervicotomy often allows removing goitre with a mediastinal extension. However, intraoperative enlargement may be necessary, with increased operating time, hospital stay and morbidity.


An enzyme-linked double antibody immunoassay to measure murine immunoglobulins--its application to determine the specific activity of radiolabeled monoclonal antibodies.
A sensitive, simple and reproducible biotin-avidin amplified double antibody immunoassay to quantitate low concentrations of mouse immunoglobulins is described. The assay is a useful technique to measure trace levels of murine monoclonal antibodies in culture supernatants of hybridoma cells metabolically labeled with radioactive isotopes. A combination of radioactive counting and measurement of the absorbance of a peroxidase catalyzed reaction permits accurate determination of the specific radioactivity of labeled monoclonal antibodies.


Yeasts from Chinese strong flavour Daqu samples: isolation and evaluation of their potential for fortified Daqu production.
In total, 16 yeast were isolated from Chinese strong flavour Daqu samples and underwent RAPD analysis and identification. Totally, 11 different species were identified among these isolates including Saccharomyces cerevisiae, Hanseniaspora vineae, Pichia kluyveri, Trichosporon asahii, Wickerhamomyces anomalus, Kluyveromyces lactis, Yarrowia lipolytica, Wickerhamomyces mori, Galactomyces geotrichum, Dabaryomyces hansenii, and Saccharomyces kudriavzevii. To understand the impact of these yeast strains on the quality and flavour of Daqu, we then assessed volatile compounds associated with Daqu samples fermented with corresponding strains. These analyses revealed strain YE006 exhibited the most robust ability to produce ethanol via fermentation but yielded relatively low quantities of volatile compounds, whereas strain YE010 exhibited relatively poor fermentation efficiency but produced the greatest quantity of volatile compounds. These two yeast strains were then utilized in a mixed culture to produce fortified Daqu, with the optimal inoculum size being assessed experimentally. These analyses revealed that maximal fermentation, saccharifying, liquefying, and esterifying power as well as high levels of volatile compounds were achieved when using a 2% inoculum composed of YE006/YE010 at a 1:2 (v/v) ratio. When the liquor prepared using this optimized fortified Daqu was compared to unfortified control Daqu, the former was found to exhibit significantly higher levels of flavour compounds and better sensory scores. Overall, our findings may provide a reliable approach to ensuring Daqu quality and improving the consistency and flavour of Chinese strong-flavour liquor through bioaugmentation.


[Gas-chromatographic determination of insecticidal chlorinated hydrocarbons using the GCHF 18.3-6 gas chromatograph with an attached electron detector].
The authors describe the gas chromatographic determination of residues of insecticidal chlorinated hydrocarbons in foods by means of the GCHF 18.3-6 gas chromatograph with electron attachment detector of the VEB Chromatron Berlin which is most frequently available in the GDR for routine work. Furthermore, the authors deal with possibilities of identifying and confirming residues of chlorinated hydrocarbons with the aid of chemical reactions.


Fractures in previously abnormal parts.
This paper discussed fractures in defective or deformed bones, in stiff, wasted or anaesthetic limbs and at the ends of metal implants. Suggestions are made as to how treatment should be modified in these situations.


Conformation, thermodynamics and stoichiometry of HSA adsorbed to colloidal CdSe/ZnS quantum dots.
Water-soluble luminescent colloidal quantum dots (QDs) have attracted great attention in biological and medical applications. In particular, for any potential in vivo application, the interaction of QDs with human serum albumin (HSA) is crucial. As a step toward the elucidation of the fate of QDs introduced to organism, the interactions between QDs and HSA were systematically investigated by various spectroscopic techniques under the physiological conditions. It was proved that binding of QDs and HSA is a result of the formation of QDs-HSA complex and electrostatic interactions play a major role in stabilizing the complex. The modified Stern-Volmer quenching constant K(a) at different temperatures and corresponding thermodynamic parameters DeltaH, DeltaG and DeltaS were calculated. Furthermore, the site marker competitive experiments revealed that the binding location of QDs with HSA is around site I, centered at Lys199. The conformational changes of HSA induced by QDs have been analyzed by means of CD and FT-IR. The results suggested that HSA underwent substantial conformational changes at both secondary and tertiary structure levels. The stoichiometry of HSA attached to QDs was obtained by dynamic light scattering (DLS) and zeta-potential.


Autologous fat transplantation for the temporalis muscle flap donor site: our experience with 45 cases.
Temporal depression after temporalis muscle flap transposition is characterized by a concavity of the soft tissue and associated with the relief of the orbital rim and zygomatic arch. The purpose of this study was to describe the use of autologous fat grafting for the treatment of postsurgical temporal contour deformities. Between March 2008 and April 2011, 45 patients were treated with lipofilling. A virtual 3-dimensional preoperative assessment was used to objectively quantify the loss of volume of the affected side. Two different methods were used to evaluate the surgical outcomes. A noticeable soft tissue augmentation of the temporal region was noted in all cases. In 35 patients, a second procedure was required and in 1 patient, a third procedure was required. The final result was assessed as fully satisfactory by 39 patients (86.6%), as satisfactory by 5 patients (11.1%), and as unsatisfactory by 1 patient (2.2%). We believe that structural fat grafting at the temporalis muscle flap donor site is an effective technique that provides a high satisfaction rate and only a few complications.


Wave solutions for the deterministic non-reducible n-type epidemic.
A model is formulated to describe the spatial spread of an epidemic involving n types of individual. This encompasses the measles, host-vector and carrier-borne epidemics, and in addition rabies involving several species of animal. The existence, uniqueness and non-existence of wave solutions for different speeds are established for this model.


Electrophysiologic spectrum of atrioventricular nodal behavior in patients with atrioventricular nodal reentrant tachycardia undergoing selective fast or slow pathway ablation.
The objective of this report is to delineate the atrioventricular (AV) nodal electrophysiologic behavior in patients undergoing fast or slow pathway ablation for control of their AV nodal reentrant tachycardia (AVNRT). One hundred sixteen consecutive patients with symptomatic AVNRT were included. Twenty-two patients underwent fast pathway ablation with complete abolition of AVNRT in all and development of complete AV block in five patients. Of 17 patients with intact AV conduction postablation, 12 had demonstrated antegrade dual pathway physiology during baseline study, which was maintained in three and lost in nine patients postablation. Two patients with successful fast pathway ablation developed uncommon AVNRT necessitating a slow pathway ablation. Twenty-one patients demonstrated both common and uncommon forms of AV nodal reentry during baseline study. The earliest site of atrial activation was close to the His-bundle recording site (anterior interatrial septum) during common variety and the coronary sinus ostium (posterior interatrial septum) during the uncommon AV nodal reentry in all 21 patients. Ninety-six patients underwent successful slow pathway ablation. Among these, the antegrade dual pathway physiology demonstrable during baseline study (60 patients) was maintained in 25 and lost in 35 patients postablation. These data suggest that: (1) dual pathway physiology may persist after successful ablation, which might be a reflection of multiple reentrant pathways in patients with AVNRT; and (2) the retrograde pathways during common and uncommon AVNRT have anatomically separate atrial breakthroughs. These findings have important electrophysiologic implications regarding the prevailing concept of the AV nodal physiology in patients with AVNRT.


Neocortical transplants grafted into the newborn rat brain demonstrate a blood-brain barrier to macromolecules.
Vascular permeability was examined in fetal neocortical transplants grafted into the cerebral cortex of newborn rats. Methods based on the histochemical labeling of intravenously administered horseradish peroxidase or on the immunocytochemical demonstration of endogenous immunoglobulin showed the presence of a blood barrier within the transplants.


Community vision screening in preschoolers: initial experience using the Plusoptix S12C automated photoscreening camera.
Amblyopia is the leading cause of monocular vision impairment in children. Early intervention is critical to prevent permanent vision impairment. Preschool vision screening programs in Canada are limited. This study reports the initial results of a community-wide vision screening program for preschoolers using the Plusoptix S12C Photoscreener (Plusoptix Inc, Nuremburg, Germany). Cross-sectional. For this study, 1443 children aged 18-59 months were recruited and screened in various community settings in London, Ontario. Participants were screened with the Plusoptix S12C device from September 2015 to May 2016. Data were analyzed for percentage of children referred for amblyogenic risk factors using the Arnold 2012 referral criteria. Referral, inconclusive results, follow-up rate, and positive predictive value were reported. Data from 1321 children were analyzed. Mean age of children meeting the inclusion criteria was 34.1 ± 9.6 (18-58) months. One hundred and nineteen children were referred to an optometrist for a comprehensive eye exam; 39 (3.0%) were inconclusive screens. The referral rate for children detected with amblyogenic risk factors was 6.1%. Forty (50.0%) children were documented as complying with the follow-up examination. The positive predictive value was 81.8%. Our community-wide vision screening program identified in a timely, manner, 80 preschoolers with amblyogenic risk factors previously unknown to be present. Results identified children with amblyogenic risk factors that may have gone undetected. This program could serve as a model for consideration by policy makers.


Chemoprevention and modern cancer prevention.
Chemoprevention is a new area of research emphasis in cancer control. The rationale is based on the accumulation of laboratory and epidemiological data indicating that various agents may halt or reverse cancer progression in animals and may reduce risks in humans. For planning purposes, research leads are submitted to a strategic system of staging with defined criteria and decision points. A research lead that enters an intervention stage must evolve through a series of phases of testing and evaluation. Human intervention clinical trials have begun to test the hypothesis that certain agents can lower cancer incidence.


Curcumin, the main active constituent of turmeric (Curcuma longa L.), induces apoptosis in hepatic stellate cells by modulating the abundance of apoptosis-related growth factors.
In order to elucidate the mechanism of action of curcumin against hepatic fibrosis, cultured rat hepatic stellate cells (HSC) (HSC-T6) were incubated with curcumin for 24 h, after which apoptosis was measured by flow-cytometry. The protein levels of the pro-apoptotic factors Fas and p53b as well as of the anti-apoptotic factor Bcl-2 were monitored by immunocytochemical ABC staining after incubation with curcumin for 24 h. In the case of 20 μM curcumin, not only was the respective apoptosis index increased, but also the abundance of the pro-apoptotic factors Fas and p53 were amplified, whereas that of the anti-apoptotic factor Bcl-2 decreased. All these effects were highly reproducible (P<0.05). Consequently, curcumin has an up-regulating effect on pro-apoptotic factors like Fas and p53 as well as a down-regulating effect of the anti-apoptotic factor Bcl-2, thus inducing apoptosis in HSC.


Evidence for hunter-gatherer impacts on raven diet and ecology in the Gravettian of Southern Moravia.
The earlier Gravettian of Southern Moravia-the Pavlovian-is notable for the many raven bones (Corvus corax) documented in its faunal assemblages. On the basis of the rich zooarchaeological and settlement data from the Pavlovian, previous work suggested that common ravens were attracted by human domestic activities and subsequently captured by Pavlovian people, presumably for feathers and perhaps food. Here, we report independent δ15N, δ13C and δ34S stable isotope data obtained from 12 adult ravens from the Pavlovian key sites of Předmostí I, Pavlov I and Dolní Věstonice I to test this idea. We show that Pavlovian ravens regularly fed on larger herbivores and especially mammoths, aligning in feeding preferences with contemporaneous Gravettian foragers. We argue that opportunistic-generalist ravens were encouraged by human settlement and carcass provisioning. Our data may thus provide surprisingly early evidence for incipient synanthropism among Palaeolithic ravens. We suggest that anthropogenic manipulation of carrion supply dynamics furnished unique contexts for the emergence of human-oriented animal behaviours, in turn promoting novel human foraging opportunities-dynamics which are therefore important for understanding early hunter-gatherer ecosystem impacts.


Staphylococcal cassette chromosome mec: recent advances and new insights.
Staphylococcal cassette chromosome (SCC) elements are complex mobile genetic elements that often carry antimicrobial resistance and in some cases virulence-associated genes. In addition to SCCmec, which harbours the methicillin resistance gene mec, many different SCC elements have been identified in staphylococci. Recent findings have significantly enhanced our understanding of the diversity of SCCmec elements and their contribution to the evolution of MRSA and are the focus of this short review. This includes the identification of (i) novel mec genes and allelic variants, (ii) an extensive array of ccr and mec complex genes as well as SCCmec, SCC and pseudo SCC/SCCmec elements and composite islands (CIs) in staphylococci, (iii) potential mec, SCC and SCCmec precursors among distinct coagulase-negative staphylococcal species, and (iv) SCC encoded virulence-associated genes. Due to their complex nature and increasing diversity, detailed characterisation of SCC and SCCmec elements and CIs represents a unique challenge but is vital for effective epidemiological typing and tracking of MRSA and other staphylococci and to enhance our understanding of the origins and evolution of MRSA.


A technique of extensile exposure for total hip arthroplasty.
A technique of trochanteric osteotomy that allows extensile exposure of the hip and wide exposure of the proximal femoral diaphysis for total joint replacement is described. Pathologic conditions of the shaft encountered during arthroplasty can therefore be addressed. The approach is based on the preservation of an intact musculoosseous-muscular sleeve comprised of the gluteus medius, greater trochanter, and vastus lateralis and allows physiologic reconstruction of the hip's soft tissue envelope. This versatile approach is particularly useful in revision surgery and in difficult primary interventions where leg length is adjusted. The surgical technique, indications, and advantages are described. Early clinical results of 90 cases are presented.


[Polymorphisms of IL-23 receptor gene are associated with susceptibility to pulmonary tuberculosis and drug-resistant pulmonary tuberculosis].
To explore the associations of interleukin-23 (IL-23) receptor gene polymorphisms, susceptibility to pulmonary tuberculosis and drug-resistant pulmonary tuberculosis (TB). For this paired case-control study, 13 single nucleotide polymorphisms (SNPs) in IL-23R gene were genotyped by multiplex SNaPshot with samples from 250 pairs of culture positive pulmonary TB patients and healthy controls. And the relationship between genotype, allele, haplotype and susceptibility to pulmonary tuberculosis was analyzed. Two SNPs of IL-23R gene (rs10889677 and rs7518660) (OR = 1.53, 95% CI: 1.01-2.31; OR = 6.25, 95% CI: 3.85-10.00) were significantly associated with susceptibility to pulmonary TB and one SNP (rs11465802) (OR = 2.90; 95% CI: 1.69-4.98) was associated with drug-resistant pulmonary TB in the Chinese Uygur population. Two SNPs of IL-23R gene, rs10889677 and rs7518660, may be the risk factors of pulmonary tuberculosis. And rs11465802 may be a risk factor of drug-resistant pulmonary tuberculosis in Chinese Uygur population.


Supramolecular One-Dimensional n/p-Nanofibers.
Currently, there is a broad interest in the control over creating ordered electroactive nanostructures, in which electron donors and acceptors are organized at similar length scales. In this article, a simple and efficient procedure is reported en-route towards the construction of 1D arrays of crystalline pristine C60 and phenyl-C61-butyric acid methyl ester (PCBM) coated onto supramolecular fibers based on exTTF-pentapeptides. The resulting n/p-nanohybrids have been fully characterized by a variety of spectroscopic (FTIR, UV-Vis, circular dichroism, Raman and transient absorption), microscopic (AFM, TEM, and SEM), and powder diffraction (X-ray) techniques. Our experimental findings document the tendency of electroactive exTTF-fibers to induce the crystallization of C60 and PCBM, on one hand, and to afford 1D n/p-nanohybrids, on the other hand. Furthermore, photogenerated radical ion pairs, formed upon visible light irradiation of the n/p-nanohybrids, feature lifetimes on the range of 0.9-1.2 ns.


Robustness analysis of cellular memory in an autoactivating positive feedback system.
Cellular memory is a ubiquitous phenomenon in cell biology. Using numerical simulation and theoretical analysis, we explored the robustness of cellular memory to intrinsic noise in a transcriptional positive feedback system. Without noise, the system could create two stable steady states and function as a memory module. Memory robustness index and mean first-passage time were used to quantify the robustness of memory. Large cell size and strong cooperativity in binding enhanced memory storage remarkably. Adding a second positive feedback loop improved persistent memory significantly, whereas including a negative one destabilized memory storage. These are consistent with experimental observations. We interpret why positive feedback loops are actively involved in epigenetic memory from a dynamical systems perspective.


Biodistribution and predictive hepatic gene expression of intravenous iron sucrose.
We have examined iron biodistribution and hepatic gene expression in rats following administration of the generic Iron Sucrose Azad (ISA) or the reference iron sucrose drug Venofer®. ISA and Venofer® were administered intravenously to normal, non-anemic, male rats at 15 mg/kg (a supra-therapeutic dose-level). To evaluate biodistribution, tissue iron levels were determined over 28 days for plasma, liver, spleen, bone marrow, heart, kidney, lung and stomach using a validated ICP-MS method. Hepatic gene expression was evaluated by microarray analysis of mRNA from samples taken 24 h after drug administration. Iron concentration/time profiles for plasma and tissues were quantitatively similar for ISA and Venofer. Following administration, circulating iron levels briefly exceeded transferrin binding capacity and there was a transient increase in hepatic iron. Bone marrow iron levels remained elevated throughout the study. No increases in tissue iron levels were observed in the heart, stomach or lungs. Spleen iron levels increased over the course of the study in treated and control rats. Small, transient increases were recorded in the kidneys of treated rats. The effects of ISA and Venofer® on hepatic gene transcription were similar. Principal components analysis showed that there was no systematic effect of either treatment on transcriptional profiles. Only a small number of genes showed significant modulation of expression. No transcriptional pattern matches with toxicity pathways were found in the ToxFX database for either treatment. No modulation of key genes in apoptosis, inflammation or oxidative stress pathways was detected. These findings demonstrated that the biodistribution of administered iron is essentially similar for Iron Sucrose Azad and Venofer®, that iron sucrose partitions predominantly into the liver, spleen and bone marrow, and that hepatic gene expression studies did not provide any evidence of toxicity in animals treated at a supra-therapeutic dose-level.


[Radiomics-AI-based image analysis].
Radiomics deals with the statistical analysis of radiologic image data. In this article, radiomics is introduced and some of its applications are presented. In particular, an example is used to demonstrate that pathology and radiology can work together for better diagnoses. There is no denying that artificial intelligence will find its place in radiology (and pathology). Deep learning in particular will increasingly find applications. However, the impact on clinical routine is more long term and probably gradual, so AI will initially only be used in the form of specialized tools to support everyday clinical practice until methods and programs improve to the extent that AI can also take on more general diagnoses. However, this will not replace pathologists and radiologists in the long term, but rather turn them into "information specialists" who interpret the results obtained and integrate them into clinical contours.