Removing the needle from the haystack: Enrichment of Wolbachia endosymbiont transcripts from host nematode RNA by Cappable-seq™.
Efficient transcriptomic sequencing of microbial mRNA derived from host-microbe associations is often compromised by the much lower relative abundance of microbial RNA in the mixed total RNA sample. One solution to this problem is to perform extensive sequencing until an acceptable level of transcriptome coverage is obtained. More cost-effective methods include use of prokaryotic and/or eukaryotic rRNA depletion strategies, sometimes in conjunction with depletion of polyadenylated eukaryotic mRNA. Here, we report use of Cappable-seq™ to specifically enrich, in a single step, Wolbachia endobacterial mRNA transcripts from total RNA prepared from the parasitic filarial nematode, Brugia malayi. The obligate Wolbachia endosymbiont is a proven drug target for many human filarial infections, yet the precise nature of its symbiosis with the nematode host is poorly understood. Insightful analysis of the expression levels of Wolbachia genes predicted to underpin the mutualistic association and of known drug target genes at different life cycle stages or in response to drug treatments is typically challenged by low transcriptomic coverage. Cappable-seq resulted in up to ~ 5-fold increase in the number of reads mapping to Wolbachia. On average, coverage of Wolbachia transcripts from B. malayi microfilariae was enriched ~40-fold by Cappable-seq. Additionally, this method has an additional benefit of selectively removing abundant prokaryotic ribosomal RNAs.The deeper microbial transcriptome sequencing afforded by Cappable-seq facilitates more detailed characterization of gene expression levels of pathogens and symbionts present in animal tissues.


Mechanisms of integral membrane protein insertion and folding.
The biogenesis, folding, and structure of α-helical membrane proteins (MPs) are important to understand because they underlie virtually all physiological processes in cells including key metabolic pathways, such as the respiratory chain and the photosystems, as well as the transport of solutes and signals across membranes. Nearly all MPs require translocons--often referred to as protein-conducting channels--for proper insertion into their target membrane. Remarkable progress toward understanding the structure and functioning of translocons has been made during the past decade. Here, we review and assess this progress critically. All available evidence indicates that MPs are equilibrium structures that achieve their final structural states by folding along thermodynamically controlled pathways. The main challenge for cells is the targeting and membrane insertion of highly hydrophobic amino acid sequences. Targeting and insertion are managed in cells principally by interactions between ribosomes and membrane-embedded translocons. Our review examines the biophysical and biological boundaries of MP insertion and the folding of polytopic MPs in vivo. A theme of the review is the under-appreciated role of basic thermodynamic principles in MP folding and assembly. Thermodynamics not only dictates the final folded structure but also is the driving force for the evolution of the ribosome-translocon system of assembly. We conclude the review with a perspective suggesting a new view of translocon-guided MP insertion.


From knowledge-based potentials to combinatorial lead design in silico.
Computational methods are becoming increasingly used in the drug discovery process. In this Account, we review a novel computational method for lead discovery. This method, called CombiSMoG for "combinatorial small molecule growth", is based on two components: a fast and accurate knowledge-based scoring function used to predict binding affinities of protein-ligand complexes, and a Monte Carlo combinatorial growth algorithm that generates large numbers of low-free-energy ligands in the binding site of a protein. We illustrate the advantages of the method by describing its application in the design of picomolar inhibitors for human carbonic anhydrase.


Juvenile myelomonocytic leukemia: who's the driver at the wheel?
Juvenile myelomonocytic leukemia (JMML) is a unique clonal hematopoietic disorder of early childhood. It is classified as an overlap myeloproliferative/myelodysplastic neoplasm by the World Health Organization and shares some features with chronic myelomonocytic leukemia in adults. JMML pathobiology is characterized by constitutive activation of the Ras signal transduction pathway. About 90% of patients harbor molecular alterations in 1 of 5 genes (PTPN11, NRAS, KRAS, NF1, or CBL), which define genetically and clinically distinct subtypes. Three of these subtypes, PTPN11-, NRAS-, and KRAS-mutated JMML, are characterized by heterozygous somatic gain-of-function mutations in nonsyndromic children, whereas 2 subtypes, JMML in neurofibromatosis type 1 and JMML in children with CBL syndrome, are defined by germline Ras disease and acquired biallelic inactivation of the respective genes in hematopoietic cells. The clinical course of the disease varies widely and can in part be predicted by age, level of hemoglobin F, and platelet count. The majority of children require allogeneic hematopoietic stem cell transplantation for long-term leukemia-free survival, but the disease will eventually resolve spontaneously in ∼15% of patients, rendering the prospective identification of these cases a clinical necessity. Most recently, genome-wide DNA methylation profiles identified distinct methylation signatures correlating with clinical and genetic features and highly predictive for outcome. Understanding the genomic and epigenomic basis of JMML will not only greatly improve precise decision making but also be fundamental for drug development and future collaborative trials.


Global shape information increases but color information decreases the composite face effect.
The separation of visual shape and surface information may be useful for understanding holistic face perception--that is, the perception of a face as a single unit (Jiang, Blanz, & Rossion, 2011, Visual Cognition, 19, 1003-1034). A widely used measure of holistic face perception is the composite face effect (CFE), in which identical top face halves appear different when aligned with bottom face halves from different identities. In the present study the influences of global face shape (ie contour of the face) and color information on the CFE are investigated, with the hypothesis that global face shape supports but color impairs holistic face perception as measured in this paradigm. In experiment 1 the CFE is significantly increased when face stimuli possess natural global shape information than when cropped to a generic (ie oval) global shape; this effect is not found when the stimuli are presented inverted. In experiment 2 the CFE is significantly decreased when face stimuli are presented with color information than when presented in grayscale. These findings indicate that grayscale stimuli maintaining natural global face shape information provide the most adept measure of holistic face perception in the behavioral composite face paradigm. More generally, they show that reducing different types of information diagnostic for individual face perception can have opposite effects on the CFE, illustrating the functional dissociation between shape and surface information in face perception.


An unprecedented {CuTe} core incorporated in a 36-tungsto-4-silicate polyoxometalate with visible light-driven catalytic hydrogen evolution activity.
We report an unprecedented {CuII14TeIV10} core containing the novel μ,μ-/μ6-TeIVO32- mode and TeIVO44- embedded within a 36-tungsto-4-silicate POT shell, which constitutes the first example of a tellurous copper cluster in POMs. The structure-stabilizing and templating effects of tellurite anions are crucial for this assembly. Moreover, its visible light-driven catalytic H2 evolution activity and related quenching mechanism are demonstrated, and extensive stability studies are presented.


Up-regulation of GIPC2 in human gastric cancer.
GIPC1/GIPC, GIPC2, and GIPC3 are a family of central PDZ-domain proteins. GIPC1/GIPC interacts with TGFbeta type III receptor, receptor tyrosine kinase TrkA, integrin alpha6A subunit, and GTPase-activating protein RGS-GAIP, while Xenopus homologue of human GIPCs interacts with Frizzled-3 (FZD3) class of WNT receptor. Here, we investigated expression of GIPC2 mRNA in human gastric, pancreatic, and breast cancer cell lines. GIPC2 mRNA was relatively highly expressed in OKAJIMA, TMK1, MKN45, and KATO-III cells derived from diffuse type of gastric cancer, but was almost undetectable in MKN7, MKN28, and MKN74 cells derived from intestinal type of gastric cancer as well as in other cell lines derived from pancreatic and breast cancer. Tumor necrosis factor alpha and interferon gamma, which are elevated in gastric mucosa with Helicobacter pylori infection, did not affect the expression level of GIPC2 mRNA in MKN45 cells. Up-regulation of GIPC2 mRNA was detected in 7 out of 10 cases of primary gastric cancer by using cDNA-PCR, and in 4 out of another 8 cases of primary gastric cancer by using expression array filter hybridization. GIPC2 might play important roles in human gastric cancer through modulation of growth factor signaling or cell adhesion.


Neurostimulation for childhood epilepsy.
The experience with neurostimulation for childhood epilepsy is far less extensive than for adults. Nevertheless, the implementation of these techniques could be of great value, especially considering the detrimental effects of ongoing seizures on the developing brain. In this review, we discuss the available evidence for neurostimulation for childhood epilepsy. Vagus nerve stimulation (VNS) is the most studied neurostimulation modality in children. Based on mostly retrospective, open-label studies, we can conclude that VNS has a similar safety and efficacy profile in children compared to adults. Although there is little available evidence for deep brain stimulation (DBS) and responsive neurostimulation (RNS) in children, both DBS and RNS show promise in reducing seizure frequency with few complications. The implementation of non-invasive techniques with a more appealing safety profile has gained interest. Small randomized control trials and open-label studies have investigated transcranial direct current simulation for childhood epilepsy, demonstrating promising but inconsistent findings.


The therapeutic validity and effectiveness of physiotherapeutic exercise following total hip arthroplasty for osteoarthritis: A systematic review.
To assess the therapeutic validity and effectiveness of physiotherapeutic exercise interventions following total hip arthroplasty (THA) for osteoarthritis. The databases Embase, MEDLINE, Cochrane Library, CINAHL and AMED were searched from inception up to February 2017. Articles reporting results of randomized controlled trials in which physiotherapeutic exercise was compared with usual care or with a different type of physiotherapeutic exercise were included, with the applied interventions starting within six months after THA. Only articles written in English, German or Dutch were included. Therapeutic validity (using the CONTENT scale) and risk of bias (using both the PEDro scale and the Cochrane Collaboration's tool) were assessed by two researchers independently. Characteristics of the physiotherapeutic exercise interventions and results about joint and muscle function, functional performance and self-reported outcomes were extracted. Of the 1124 unique records retrieved, twenty articles were included. Only one article was considered to be of high therapeutic validity. Description and adequacy of patient selection were the least reported items. The majority of the articles was considered as having potentially high risk of bias, according to both assessment tools. The level of therapeutic validity did not correspond with the risk of bias scores. Because of the wide variety in characteristics of the physiotherapeutic exercise and control interventions, follow-up length and outcome measures, limited evidence was found on the effectiveness of physiotherapeutic exercise following THA. The insufficient therapeutic validity and potentially high risk of bias in studies involving physiotherapeutic exercise interventions limit the ability to assess the effectiveness of these interventions following THA. Researchers are advised to take both quality scores into account when developing and reporting studies involving physiotherapeutic exercise. Uniformity in intervention characteristics and outcome measures is necessary to enhance the comparability of clinical outcomes between trials.


Heterologous Immune Responses of Serum IgG and Secretory IgA Against the Spike Protein of Endemic Coronaviruses During Severe COVID-19.
Defining immune correlates of disease severity is important to better understand the immunopathogenesis in COVID-19. Here we made use of a protein microarray platform to detect IgG- and IgA-reactive antibodies in sera and saliva respectively, and assess cross-reactivity between SARS-CoV-2 and endemic coronaviruses (eCoVs). IgG responses against the full protein of spike, but not the S1 subunit, were significantly higher in convalescent sera of patients with severe disease compared to mild disease and healthy controls. In addition, we detected reactivity of secretory IgA to eCoVs in saliva of patients with severe disease, not present in patients with moderate disease or seropositive healthy controls. These heterologous immune responses are in line with non-protective cross-reactivity, and support a potential role for immune imprinting in the pathogenesis of severe COVID-19.


Cancer Control at the District Hospital Level in Sub-Saharan Africa: An Educational and Resource Needs Assessment of General Practitioners.
The WHO framework for early cancer diagnosis highlights the need to improve health care capacity among primary care providers. In Rwanda, general practitioners (GPs) at district hospitals (DHs) play key roles in diagnosing, initiating management, and referring suspected patients with cancer. We sought to ascertain educational and resource needs of GPs to provide a blueprint that can inform future early cancer diagnosis capacity-building efforts. We administered a cross-sectional survey study to GPs practicing in 42 Rwandan DHs to assess gaps in cancer-focused knowledge, skills, and resources, as well as delays in the referral process. Responses were aggregated and descriptive analysis was performed to identify trends. Survey response rate was 76% (73 of 96 GPs). Most responders were 25 to 29 years of age (n = 64 [88%]) and 100% had been practicing between 3 and 12 months. Significant gaps in cancer knowledge and physical exam skills were identified-88% of respondents were comfortable performing breast exams, but less than 10 (15%) GPs reported confidence in performing pelvic exams. The main educational resource requested by responders (n = 59 [81%]) was algorithms to guide clinical decision-making. Gaps in resource availability were identified, with only 39% of responders reporting breast ultrasound availability and 5.8% reporting core needle biopsy availability in DHs. Radiology and pathology resources were limited, with 52 (71%) reporting no availability of pathology services at the DH level. The current study reveals significant basic oncologic educational and resource gaps in Rwanda, such as physical examination skills and diagnostic tools. Capacity building for GPs in low- and middle-income countries should be a core component of national cancer control plans to improve accurate and timely diagnosis of cancer. Continuing professional development activities should address and focus on context-specific educational gaps, resource availability, and referral practice guidelines.


Pushing the envelope: Advancing Canadian healthcare payment models through evaluation.
When health systems aim to improve, two key considerations tend to be front and centre: cost and quality. On the cost side, health spending in Canada continues to rise. On the quality side, improvement is needed across the country. As the primary funder of healthcare, governments' historical role has focused on managing costs through their powers to set budgets, decide who gets paid, and how. Increasingly, governments are recognizing that the ways in which they choose to pay providers and organizations can also have an impact on the quality of care provided. Using Ontario as an example, we present a Canadian vision for modernizing how healthcare is organized and reimbursed and for using evidence and evaluation as the backbone for iterating new models. Realizing this vision will move Canada closer to international leadership in delivering high-quality, affordable care.


Overweight or obesity in children aged 0 to 6 and the risk of adult metabolic syndrome: A systematic review and meta-analysis.
To identify an association between overweight or obesity in early childhood and metabolic syndrome in adults. Early childhood overweight or obesity is important because it can predict metabolic syndrome in adulthood. A longer period of overweight or obesity leads to the accumulation of more risk factors. However, there are insufficient and inconsistent studies on this issue. A systematic review and meta-analysis. We followed the Meta-Analysis of Observational Studies in Epidemiology guideline, MEDLINE, EMBASE, Cochrane library and CINAHL electronic databases as well as reference lists of included studies were searched, without published date restriction. We used the Newcastle-Ottawa Scale to assess the quality of the observational studies in the systematic review, and the meta-analysis was performed using random-effects models. All of the included studies were published from 2008-2014, and the participants of this study were only Asians or Europeans. A total of 12 results from five studies were included in the meta-analysis. Overweight or obesity in early childhood was associated with a higher risk of adult metabolic syndrome compared with the controls. When confirmed in each age group (at birth, 0-2 and 2-6 years), there was a statistically significant difference before and after the age of 2 years. As a result of the meta-regression, when the age of the children increased, the effect size of adult metabolic syndrome for overweight or obesity also increased. The results confirm that the aetiology of metabolic syndrome includes long-term impacts from the early stage of life and indicate that early intervention for overweight or obesity is needed. these findings could help community and clinical health nurses recognize the risk of overweight or obesity in early life, and provide evidence to develop and implement the preventive intervention for early childhood.


[Application of continuous renal replacement therapy in the treatment of myonephropathic metabolic syndrome caused by acute lower extremity ischemia].
To summarize the experiences of using continuous renal replacement therapy in the treatment of myonephropathic metabolic syndrome caused by acute lower limb ischemia. Retrospective study of patients diagnosed acute lower limb ischemia with surgical treatment between January 2008 and December 2013, among which 22 patients with myonephropathic metabolic syndrome received continuous renal replacement therapy. Summarize the change tendency of myoglobin, urine volume and serum creatinine levels during treatment and analysis the condition changes and prognosis of the patients. Among them, 2 patients were amputated and two died after surgery. The major causes of death were acute renal failure, metabolic acidosis, circulation failure and liver failure, etc. Myoglobin was significantly higher at Day 1 after surgery than that was before surgery (P < 0.05). Urine volume was significantly lower at Day 1 after surgery than that on the day of surgery (P < 0.05). CK was significantly lower at Day 2 after surgery than the day before (P < 0.05). Hemoglobin was significantly lower at Day 1 after surgery than that before surgery (P < 0.05). Serum creatinine levels remained steady. In patients of acute lower limb ischemia with myonephropathic metabolic syndrome, early targeted continuous renal replacement therapy may decrease the serum concentrations of myoglobin and CK, improve urine volume, maintain homeostasis, prevent renal function deterioration and improve the prognosis of patients. And it is highly recommended.


Pigment Epithelial-Derived Factor Peptide Regenerated Limbus Serves as Regeneration Source for Limbal Regeneration in Rabbit Limbal Deficiency.
To demonstrate that a 44-amino acid peptide from pigment epithelial-derived factor (PEDF) induces the regeneration of limbal excision wound, and the regenerated limbus can act as the regeneration source for new limbal excisional injuries in rabbit model of limbal deficiency. Half circumference partial limbal excision was followed by PEDF peptide treatment to achieve limbal wound regeneration. Three months later, a second stage half circumference partial limbal excision removed the remaining native limbal tissue followed by PEDF peptide treatment. The structure and function of the regenerated limbus were analyzed at 3 and 6 months. Conjunctivalization was analyzed by impression cytology. Immunohistochemical analysis was performed with antibodies to corneal epithelium-associated keratin 3 (K3), conjunctival epithelium-associated keratin 13 (K13), ΔNp63α, ABCG2, and BrdU. Extensive limbal excision was performed to examine the regeneration potential of the PEDF peptide. Total limbal stem cell deficiency occurred with severe inflammation and conjunctivalization of the limbal wound and adjacent cornea in vehicle control eyes. In PEDF peptide treated eyes, the regenerated limbus prevented fibrovascular invasion and goblet cell migration into the corneal surface. Immunohistochemical staining of the regenerated limbus showed a wide distribution of cells expressing ΔNp63α and ABCG2 as in the native limbus. BrdU labeling assay revealed the presence of slow-cycling cells in the basal layer of the regenerated limbus. The PEDF peptide can heal extensive limbal excisional wounds and sustain ocular surface integrity. The addition of PEDF peptide has the potential to repair limbal excisional wounds with the recovery of normal limbus-like anatomy and function. The PEDF peptide is a potential remedy for extensive limbal injury.


Redescription of Lernaeenicus stromatei Gnanamuthu, 1953 (Copepoda: Siphonostomatoida: Pennellidae) infesting the Black Pomfret Parastromateus niger (Bloch) from Indian waters.
The parasitic copepod Lernaeenicus stromatei Gnanamuthu, 1953 infecting black pomfret, Parastromateus niger (Bloch) (Carangidae) is redescribed based on a neotype and additional fresh material obtained from hosts collected at different fish landing centers on the Chennai Coast (Tamil Nadu), Malabar Coast (Kerala), and from West Bengal, India. A female L. stromatei obtained from the Chennai Coast has been designated as a neotype and deposited in the National Zoological Collections of Zoological Survey of India (NZC-ZSI). Lernaeenicus stromatei can be identified based on the following features: A long and slender body; head anteriorly rounded, dorso-ventrally flattened and slightly longer than broad; presence of three posterior horns on the head, one median and two lateral, all sub-similar and apically rounded; and an anterior neck with an indistinct partition on the dorsal side, indicating thoracic segments, and a three-jointed antennule.


[Case of juvenile parkinsonism in pregnancy].
A 29-year-old woman with two sons developed a rest tremor and motor slowness in her right limbs. She was diagnosed as Parkinson's disease (PD) and was treated with anti-cholinergic drugs. After three years of taking a dopamine agonist (cabergoline, 4 mg per day), she became pregnant. The patient and her husband decided to have an abortion because they worried that the cabergoline might have harmed the fetus. The patient hoped to prepare for future planned birth, so we canceled the cabergoline and gradually increased her carbidopa/levodopa dose. Her motor disability gradually worsened during the pregnancy, and she developed prominent bradykinesia while taking a high dose of carbidopa/levodopa (1,000 mg per day) and a continuous infusion of levodopa. A cesarean section was performed, and the patient gave birth to a healthy baby. After the delivery, she was treated with pramipexole (2 mg per day), and her bradykinesia decreased. The initial anti-PD medication schedule for fertile female PD patients should be carefully considered to lessen the harm to the fetus, especially during organogenesis. Motor disability may worsen during pregnancy, and appropriate childcare support should be prepared.


Transient splenial lesion due to non-cirrhotic hyperammonaemia in dengue fever.
Transient splenial lesion(TSL) is seen in a variety of conditions and is detectable only on MRI of the brain. Dengue fever (DF) is a common viral infection encountered in the tropics. The affected patients may face neurological complications like encephalopathy and intracranial haemorrhage, or even ischaemic stroke. Non-cirrhotic hyperammonaemia is a rare scenario; and its occurrence in DF is unknown. The patient being described had DF and developed dysarthria. His MRI brain showed splenial hyperintensity. Further evaluation revealed non-cirrhotic hyperammonaemia. To the best of our knowledge, TSL due to non-cirrhotic hyperammonaemia in DF is an unreported scenario.


Syk tyrosine kinase participates in beta1-integrin signaling and inflammatory responses in airway epithelial cells.
The protein tyrosine kinase Syk is critically involved in immunoreceptor signaling in hematopoietic cells. Recent studies demonstrate Syk expression in nonhematopoietic cells, including fibroblasts, endothelial cells, hepatocytes, and breast epithelium. However, the role of Syk in these cells is uncertain. We hypothesized that Syk is expressed in respiratory epithelial cells (EC) and that it functions as a signaling molecule involved in inflammatory responses in the epithelium. With the use of immunohistochemistry, Western blot, PCR, and laser scanning confocal microscopy, Syk was detected in human, rat, and mouse bronchial epithelium in situ and in cultured human bronchial EC in primary cells and the cell lines HS-24 and BEAS-2B. Syk-dependent signaling pathways in EC were initiated by engagement of beta1-integrin receptors. Stimulation of beta1-integrin receptors by fibronectin or antibody cross-linking caused redistribution of Syk from a cytoplasmic to plasma membrane localization. In stimulated cells, Syk and beta1-integrin colocalized. In addition, following beta1-integrin receptor engagement, tyrosine phosphorylation of Syk was observed. Expression of the intercellular adhesion molecule-1 (ICAM-1) and production of IL-6, both important molecules in lung inflammation, was downregulated in EC treated with Syk small interfering RNA or Syk inhibitor piceatannol. We propose that Syk is involved in signaling pathways induced by integrin engagement in airway EC. Syk-mediated signaling regulates IL-6 and ICAM-1 expression and may be important in the pathophysiology of lung inflammation.


[Detection of the IS2404 insertion sequence and ketoreductase produced by Mycobacterium ulcerans in the aquatic Heteroptera in the health districts of Dabou and Tiassalé in Côte d'Ivoire].
Buruli ulcer (BU) disease, caused by Mycobacterium ulcerans, is a major public health problem in Côte d'Ivoire. Until now, the mode of BU transmission was unknown, but recent studies implicate aquatic Heteroptera in the chain of transmission. This study was launched in Côte d'Ivoire to search for specific genetic markers for M. ulcerans in these bugs, including the insertion sequence IS2404 and ketoreductase (Kr), both involved in the synthesis of mycolactone, a toxin produced by these mycobacteria. Samples of aquatic Heteroptera were collected monthly with deep nets from ponds near villages in the health districts of Dabou and Tiassalé. After identification and enumeration of the bugs, batches of the same taxon underwent real-time PCR to search for the IS2404 target and Kr. Saliva of 69 specimens of Diplonychus sp randomly selected in the samples was also analyzed by PCR. In all, 283 single-taxon batches were created. Thus, PCR identified 26 batches belonging to the families of Belostomatidae, Naucoridae, Corixidae, Ranatridae, and Nepidae as positive for both targets. The IS2404 insertion sequence and Kr were present in 6 of the 69 samples analyzed in the saliva of Diplonychus sp. These aquatic Heteroptera suspected of infection by M. ulcerans might release it into the environment because of their ability to fly. They might thus be the source of human contamination.


Rectus femoris muscle atrophy and recovery caused by preoperative pretibial traction in femoral shaft fractures-comparison between traction period.
Skeletal traction is performed to temporarily stabilize fracture sites before surgery in patients with femoral fracture. To date, however, there is no study evaluating the difference in the degree of the recovery, of the muscle strength, as well as muscle atrophy following skeletal traction. The purpose of this study was to compare the degree of recovery of rectus femoris muscle strength after surgery in association with muscle atrophy by analyzing the duration of preoperative tibial traction, age and sex in patients with femoral fracture. Rectus femoris muscle atrophy will progress depending on the duration of preoperative tibial traction, age and sex in patients with femoral fracture. Thirty-one patients who underwent preoperative pretibial skeletal traction and intramedullary nailing were divided into two groups according to the traction period: group A (n=12) with a duration of traction of <7 days (mean: 4.08±1.78 days) and group B (n=19) ≥7 days (mean: 13.63±7.17 days). The degree of muscle atrophy and recovery were compared between the two groups, according to age and gender. The degree of muscle atrophy was measured by the difference in thickness of the rectus femoris between pre- and post-traction using ultrasound. The degree of muscle recovery was evaluated by the Q-setting and heel off time. Clinical outcome was evaluated by the non-union rate and Lysholm score. The degree of muscle atrophy was 0.99±0.14mm in group A and 2.22±0.11mm in group B (P<0.001). The Q-setting time was 4.83±0.94 days in group A and 6.56±1.38 days in group B (P=0.001). Heel off time was also shorter in group A at 2.58±0.90 days, taking 3.72±1.27 days in group B (P=0.012). The recovery rate in the rectus femoris was significantly higher in group A than in group B (P<0.001). There was no significant difference in non-union rate between group A and B (P=0.672) but the mean Lysholm score at the last follow-up was significantly higher in group A than in group B (P=0.006). However, no significant differences were detected in the mean thickness of the rectus femoris, Q-setting, and heel off time between the different age and gender groups (P<0.05). The prolonged duration of preoperative skeletal traction indicates not only that the resulting disuse atrophy would progress further but also that the muscle atrophy would be accelerated more rapidly for shorter periods of time, based on a cut-off value of 7 days. In addition, the rate of rectus femoris muscle recovery and clinical outcomes were lower in patients undergoing traction for longer periods of time. This indicates that it would be effective for increasing the rate of the recovery and minimizing the occurrence of post surgical complications if surgeons could perform surgery at the earliest possible opportunity following traction, within seven days after the onset of trauma. IV, retrospective cohort study.


The chronically critically ill patient: pediatric considerations.
Whether defined as chronically critically ill, long-term mechanical ventilator dependent (or otherwise chronically medically supported), or medically fragile, a population of infants and children with chronic illness clearly exists. Infants and children with chronic healthcare needs are at an increased risk for physical, developmental, behavioral, and/or emotional conditions and generally require healthcare services of a type or amount beyond that of a general pediatric or adult population. This review will focus on the specific management and psychosocial needs associated with the healthcare of this subgroup of infants and children with chronic illness. Attention will be paid to defining the population, describing trends over time, reviewing their special needs, and discussing outcomes. Increased focus and an increasing quantity of resources for this subgroup of infants and children are needed, as the number of such pediatric patients continues to grow.


Pathologist's assistant (PathA) and his/her role in the surgical pathology department: a systematic review and a narrative synthesis.
In recent decades, various highly qualified individuals have increasingly performed tasks that have historically been handled by physicians with the aim of reducing their workload. Over time, however, these "physician assistants" or "physician extenders" have gained more and more responsibilities, showing that specific tasks can be performed equally skilfully by specialised health care professionals. The pathologist's assistant (PathA) is a highly qualified technician who works alongside the pathologist and is responsible for the grossing and autopsies. This profession was developed in the USA, with formal training programmes starting in 1970 when Dr. Kinney, director of the Department of Pathology of Duke University, Durham, NC, started the first dedicated course. Most institutes in the USA and Canada currently employ these technical personnel for grossing, and numerous papers published over the years demonstrate the quality of the assistance provided by the PathA, which is equal to or sometimes even better than the performance of pathologists. The PathA can be employed to carry out a wide range of tasks to assist the pathologist, such as grossing (the description and reduction of surgical specimens), judicial autopsies and administrative and supervisory practices within the laboratory or assistance in research, although the diagnosis is always the pathologist's responsibility. Since this role has already been consolidated in North America, part of the relevant literature is altogether out of date. However, the situation is different in Europe, where there is an increasing interest in PathA, mainly because of the benefits of their inclusion in anatomic pathology laboratories. In the UK, biomedical scientists (BMS, the British equivalent of PathA) are involved in many tasks both in surgical pathology and in cytopathology, which are generally performed by medically trained staff. Several papers have been recently published to highlight the role of BMS with the broader public. This report aimed to conduct a systematic review of all the articles published about the PathA/BMS and to perform a narrative synthesis. The results may contribute to the evidence for including the PAthA/BMS within a surgical pathology laboratory organisation.


Role of the English (H6R) Mutation on the Structural Properties of Aβ40 and Aβ42 Owing to the Histidine Tautomeric Effect.
As an intrinsic origin cause, histidine behaviors play a critical role in protein misfolding processes. Generally, the English (H6R) mutation will disrupt H6 interactions. However, the structural properties of Aβ40 H6R and Aβ42 H6R under the complex influence of a histidine tautomeric effect and an H6R mutation remain unclear. Therefore, we performed a replica exchange molecular dynamics simulation to unveil such structural properties. Our result showed that the H6R substitute could promote the generation of β-sheet structures in comparison to the wild type. Three β-strand structure properties were observed in Aβ40 (rδδ), Aβ42 (rεε), Aβ42 (rεδ), and Aβ42 (rδδ) with β-sheet contents of 47.5%, 37.2%, 46.9%, and 38.6%, respectively, and the dominant conformational properties of Aβ40 (rδδ), Aβ42 (rεε), Aβ42 (rεδ), and Aβ42 (rδδ) had top conformational states of 86.0%, 73.2%, 67.0%, and 56.5%, respectively. Further analysis confirmed that R6 had different mechanisms for controlling the conformational features in Aβ40 H6R and Aβ42 H6R. In the Aβ40 systems, H14 H-bond networks played a critical role in controlling the structural properties. However, in the Aβ42 systems, R6 was more important because it was directly involved in the β-strand formation and maintained the β-sheet between the N-terminus and the central hydrophobic core region. Our current study helps to elucidate the histidine tautomeric behaviors in H6R mutations, which will present opportunities to understand the correlation between with/without H6 and the Aβ40/Aβ42 H6R misfolding mechanisms.


Robocasting and Laser Micromachining of Sol-Gel Derived 3D Silica/Gelatin/β-TCP Scaffolds for Bone Tissue Regeneration.
The design and synthesis of sol-gel silica-based hybrid materials and composites offer significant benefits to obtain innovative biomaterials with controlled porosity at the nanostructure level for applications in bone tissue engineering. In this work, the combination of robocasting with sol-gel ink of suitable viscosity prepared by mixing tetraethoxysilane (TEOS), gelatin and β-tricalcium phosphate (β-TCP) allowed for the manufacture of 3D scaffolds consisting of a 3D square mesh of interpenetrating rods, with macropore size of 354.0 ± 17.0 μm, without the use of chemical additives at room temperature. The silica/gelatin/β-TCP system underwent irreversible gelation, and the resulting gels were also used to fabricate different 3D structures by means of an alternative scaffolding method, involving high-resolution laser micromachining by laser ablation. By this way, 3D scaffolds made of 2 mm thick rectangular prisms presenting a parallel macropore system drilled through the whole thickness and consisting of laser micromachined holes of 350.8 ± 16.6-micrometer diameter, whose centers were spaced 1312.0 ± 23.0 μm, were created. Both sol-gel based 3D scaffold configurations combined compressive strength in the range of 2-3 MPa and the biocompatibility of the hybrid material. In addition, the observed Si, Ca and P biodegradation provided a suitable microenvironment with significant focal adhesion development, maturation and also enhanced in vitro cell growth. In conclusion, this work successfully confirmed the feasibility of both strategies for the fabrication of new sol-gel-based hybrid scaffolds with osteoconductive properties.


Extra Corporeal Shock Wave Therapy Versus Local Corticosteroid Injection in the Treatment of Chronic Plantar Fasciitis, a Single Blinded Randomized Clinical Trial.
Plantar fasciitis is a self-limiting condition, but can be painful and disabling. Among the different treatments which exist, corticosteroid injections are effective and popular. Extracorporeal shock wave therapy (ESWT) is another treatment modality used for resistant conditions. In this study, the authors evaluated the efficacy of radial ESWT versus corticosteroid injections in the treatment of chronic plantar fasciitis. Randomized clinical trial. Physical medicine and rehabilitation research center in a university hospital. Forty patients with plantar fasciitis who did not respond to conservative treatment. Patients were allocated to radial ESWT with 2000 shock waves/session of 0.2 mJ/mm(2) (n = 20) or local methylprednisolone injections (n = 20). Pain in the morning and during the day based on a visual analog scale (VAS), functional abilities using the foot function index (FFI), and satisfaction were evaluated before treatment and at 4 and 8 weeks after treatment. Patients (average age: 42.1± 8.20) received five sessions of ESWT or single steroid injection. Changes in the VAS in morning and during the day and the FFI throughout the study period were significant in both groups (P < 0.001). ESWT group had a higher reduction in VAS in morning and better function in FFI, but these changes were insignificant statistically [FFI decreased to 19.65 ± 21.26 points (67.4% improvement) in ESWT vs 31.50 ± 20.53 points (47.7%) in injection group at week 8, P = 0.072)]. Good or excellent results in the opinions of patients were achieved in 55% of ESWT and 30% of corticosteroid injection groups (P = 0.11). Both interventions caused improvement in pain and functional ability 2 months after treatment. Although inter-group differences were not significant, the FFI was improved more with ESWT and patients were more satisfied with ESWT, thus shockwave therapy seems a safe alternative for management of chronic plantar fasciitis.


Longitudinal Visualization of Viable Cancer Cell Intratumoral Distribution in Mouse Models Using Oatp1a1-Enhanced Magnetic Resonance Imaging.
Multimodality reporter gene imaging provides valuable, noninvasive information on the fate of engineered cell populations. To complement magnetic resonance imaging (MRI) measures of tumor volume and 2-dimensional reporter-based optical measures of cell viability, reporter-based MRI may offer 3-dimensional information on the distribution of viable cancer cells in deep tissues. Here, we engineered human and murine triple-negative breast cancer cells with lentivirus encoding tdTomato and firefly luciferase for fluorescence imaging and bioluminescence imaging (BLI). A subset of these cells was additionally engineered with lentivirus encoding organic anion transporting polypeptide 1a1 (Oatp1a1) for MRI. Oatp1a1 operates by transporting gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) into cells, and it concomitantly improves BLI substrate uptake. After orthotopic implantation of engineered cells expressing or not expressing Oatp1a1, longitudinal fluorescence imaging, BLI, and 3-Tesla MRI were performed. Oatp1a1-expressing tumors displayed significantly increased BLI signals relative to control tumors at all time points (P < 0.05). On MRI, post-Gd-EOB-DTPA T1-weighted images of Oatp1a1-expressing tumors exhibited significantly increased contrast-to-noise ratios compared with control tumors and precontrast images (P < 0.05). At endpoint, tumors expressing Oatp1a1 displayed intratumoral MR signal heterogeneity not present at earlier time points. Pixel-based analysis of matched in vivo MR and ex vivo fluorescence microscopy images revealed a strong, positive correlation between MR intensity and tdTomato intensity for Oatp1a1-expressing tumors (P < 0.05), but not control tumors. These results characterize Oatp1a1 as a sensitive, quantitative, positive contrast MRI reporter gene for 3-dimensional assessment of viable cancer cell intratumoral distribution and concomitant BLI enhancement. This multimodality reporter gene system can provide new insights into the influence of viable cancer cell intratumoral distribution on tumor progression and metastasis, as well as improved assessments of anticancer therapies.


Growth rate of coeliac children is compromised before the onset of the disease.
Growth impairment has often been described in children who develop coeliac disease (CD). Based on data from the multicentre, longitudinal PreventCD study, we analysed the growth patterns of infants at genetic risk of CD, comparing those who developed CD by 6 years of age (CD 'cases', 113 infants) versus those who did not develop CD by 6 years (no CD 'controls', 831 infants). Weight and length/height were measured using a longitudinal protocol. Raw measurements were standardised, computing z-scores for length/height and weight; a linear mixed model was fitted to the data in order to compare the rate of growth in the two cohorts. Neither cases nor controls had significant growth failure. However, when the mean z-scores for weight and height were analysed, there was a difference between the two groups starting at fourth month of life. When the growth pattern in the first year was analysed longitudinally using mixed models, it emerged that children who develop CD had a significantly lower growth rate in weight z-score (-0.028/month; 95% CI -0.038 to -0.017; p<0.001) and in length/height z-score (-0.018/month; 95% CI -0.031 to -0.005; p=0.008) than those who do not develop CD. When the whole follow-up period was analysed (0-6 years), differences between groups in both weight and length/height z-scores were confirmed. The growth of children at risk of CD rarely fell below 'clinical standards'. However, growth rate was significantly lower in cases than in controls. Our data suggest that peculiar pathways of growth are present in children who develop CD, long before any clinical or serological signs of the disease appear.


The soft-tissue shaving procedure for deformity management of chronic tophaceous gout.
Gout is a condition characterized by the deposition of monosodium urate crystals in the joints or soft tissue. A gouty tophus occasionally mimics an infectious or neoplastic process. However, the conventional enucleating procedure might cause complications. In severe cases, skin necrosis and tendon or joint exposure can occur after debridements. In this series, the soft-tissue shaver is used for deformity management of the chronic tophaceous patients and the results are encouraging. From November 2000 to August 2002, 17 patients with chronic tophaceous gout were treated by the shaver technique. Suction and irrigation were performed simultaneously while the shaver was operating, and chalky deposits of sodium urate could be removed efficiently. Skin necrosis was minimized by means of proper incision planning. Also, bedside debridements and wound wet dressing were helpful for improving the outcomes. The families and patients were satisfied with the results. In conclusion, severe chronic tophaceous gout can be a surgical challenge. The soft-tissue shaving technique can be useful for cosmetic debulking of large tophi in patients with advanced chronic tophaceous gouty arthritis.


[Management of bullous pemphigoid and mucous membrane pemphigoid].
Bullous pemphigoid (BP) is the most common blistering autoimmune dermatosis and, as an age-associated disease, is also the bullous dermatosis with the highest increase in incidence in recent years due to demographic developments. Mucous membrane pemphigoid (MMP), which is less common, is a clinically and immunopathologically heterogeneous blistering autoimmune dermatosis characterized by blisters and erosions on mucous membranes. This work summarizes the manifold clinical characteristics of both diseases and provides an up-to-date overview of diagnostics and therapy of BP and SHP. A selective literature search was carried out. While eczematous, urticarial, or bullous lesions on the integument are typical for BP, MMP is characterized by pronounced, erosive mucosal changes orally, ocularly, genitoanally, tracheally or esophageally and, at most, only minor skin involvement. For diagnosis, the combination of histology, direct immunofluorescence microscopy, and serological detection of autoantibodies against the hemidesmosomal proteins BP180 and BP230 and, in MMP, also against laminin 332 is important. New pathophysiological findings and therapeutics have recently significantly expanded the range of treatment options. Due to the comorbidities of the usually elderly BP patients and the often multiple affected mucous membranes in MMP, with the risk of developing irreversible complications such as strictures and synechiae, interdisciplinary diagnosis and therapy is often required.


Occurence of Bordetella bronchiseptica in domestic cats with upper respiratory tract infections.
Bordetella bronchiseptica is a widespread Gram-negative pathogen occurring in different mammal species. It is known to play a role in the etiology of infectious atrophic rhinitis of swine, canine kennel cough, respiratory syndromes of cats, rabbits and guinea pigs, and sporadic human cases have also been reported. The aim of this article is to present the occurrence of infections caused by these bacteria in domestic cats with respiratory symptoms, as well as to conduct a molecular analysis of the flaA gene B. bronchiseptica for the purpose of ascertaining whether cats become infected with one or more bacteria strains. B. bronchiseptica was isolated from the respiratory system of 16 out of 35 domestic cats with symptoms of respiratory tract infections. Polymorphism analysis of polymerase chain reaction products of B. bronchiseptica flaA was performed to reveal the possible differences in nucleotide sequences of the flagellin gene. The phylogenetic analysis of nucleotide sequences obtained during PCR indicated that the isolates of bacteria from our own studies are characterised by 100% homology of the analysed fragment of the flaA gene, which suggests maintenance of a single genotype of these microorganisms in the cat population. Moreover, the bacteria revealed full homology with reference strain B. bronchiseptica ATCC 4617, and 99.4% homology with strain B. parapertussis ATCC 15311. This indicates that the PCR optimised for the Bordetella spp. flaA gene, combined with sequencing of amplicons obtained in PCR, is an effective diagnostic method allowing differentiation of Bordetella spp. type microorganisms.


New Distribution Records of Anopheles darlingi in Quintana Roo, Southeastern Mexico.
Anopheles darlingi is considered the main vector of malaria in the Neotropical region, so knowledge of its distribution in the Americas is highly relevant for the design of strategies for prevention and control of the illness. In Mexico, An. darlingi was recorded for the first time in 1943, and currently its distribution covers the states of Campeche, Chiapas, Quintana Roo, and Tabasco. In this study, new distribution data and observations of the abundance of An. darlingi in 14 localities of Quintana Roo, southeastern Mexico, are presented.


Pharmacological profile of the selective mitochondrial F1F0 ATP hydrolase inhibitor BMS-199264 in myocardial ischemia.
The mitochondrial F1F0 ATP synthase is responsible for the majority of ATP production in mammals and does this through a rotary catalytic mechanism. Studies show that the F1F0 ATP synthase can switch to an ATP hydrolase, and this occurs under conditions seen during myocardial ischemia. This ATP hydrolysis causes wasting of ATP that does not produce work. The degree of ATP inefficiently hydrolyzed during ischemia may be as high as 50-90% of the total. A naturally occurring, reversible inhibitor (IF-1) of the hydrolase activity is in the mitochondria, and it has a pH optimum of 6.8. Based on studies with the nonselective (inhibit both synthase and hydrolase activity) inhibitors aurovertin B and oligomycin B reduce the rate of ATP depletion during ischemia, showing that IF-1 does not completely block hydrolase activity. Oligomycin and aurovertin cannot be used for treating myocardial ischemia as they will reduce ATP production in healthy tissue. We generated a focused structure-activity relationship, and several compounds were identified that selectively inhibited the F1F0 ATP hydrolase activity while having no effect on synthase function. One compound, BMS-199264 had no effect on F1F0 ATP synthase function in submitochondrial particles while inhibiting hydrolase function, unlike oligomycin that inhibits both. BMS-199264 selectively inhibited ATP decline during ischemia while not affecting ATP production in normoxic and reperfused hearts. BMS-191264 also reduced cardiac necrosis and enhanced the recovery of contractile function following reperfusion. These data also suggest that the reversal of the synthase and hydrolase activities is not merely a chemical reaction run in reverse.


Sexuality and textuality.
Post-Freudian theories have been criticized for abandoning what is basic to psychoanalysis: the biological body and sexuality as the source of intrapsychic motivation. Arguably, however, they are more present than ever before-for example, in explanations by theorists who propose therapeutic actions beyond interpretation, presymbolic enactments of procedural memories, or disclosures of the analyst's bodily states as an aspect of intersubjectivity. By contrast, the Freudian body was always a text whose mediated meanings require interpretation, for which Freud provided eloquent guides. It is this textuality, and not sexuality, that distinguishes a psychoanalytic approach: a psycho-logic constructed according to a grammar of desire that mediates experience and creates interpretable behavior, both in action and in speech. Theoretical changes in psychoanalysis are traced historically along the dimension of textuality, the example of perversion is invoked, and the conclusion drawn that any theoretical approach, traditional or post-Freudian, that expands an understanding of textuality contributes to the science of psychoanalysis.


[Urachal patency in neonatal foals - a review of the literature].
Urachal patency is an umbilical disease in newborn foals. Etiologically, either the closure of the urachus remains absent after birth (persistent urachus) or the urachus was already closed and reopens at a later time (patent urachus). The most common causes of patent urachus are congenital defects, tearing of the navel above the predilection site, trauma, increased intravesical or abdominal pressure and umbilical infections. Patent urachus occurs more frequently in premature or weak and immunocompromised foals. Colts are more often affected than fillies. Typical clinical signs are apparent immediately after birth (persistent urachus) or 7-14 days postpartum (patent urachus). These include either dripping or a stream of urine through umbilicus during micturition as well as a moist umbilical area. The diagnosis is usually unambiguous. Typical laboratory findings are not described for patent urachus. Conservative treatment such as obliteration, cauterization or cryosurgery may be employed in cases lacking an inflammation of the urachus or other umbilical structures and when the urachal lumen measures less than 6 mm. Surgical treatment is indicated in foals with large urachal lumen, an umbilical infection or sepsis as well as when no therapeutic success is attained after a conservative treatment of 5-7 days. In most cases, prognosis is good, however complications such as umbilical inflammation, disseminating infections, and secondary joint diseases may significantly impair prognosis.


Polyclonal B cell activator associated with alpha-2-macroglobulin in the serum of patients with rheumatoid arthritis.
We investigated whether patients with rheumatoid arthritis have a polyclonal B cell activator (PBA) in their serum by using three methods: (1) the ability of any PBA to maintain the surface Ig of rabbit or human B cells in vitro; (2) the induction of blast transformation in human B lymphocyte cultures, and (3) stimulation of nude mouse spleen cells in vitro. All three methods indicated that a PBA is present in the serum of patients with rheumatoid arthritis but not in normal individuals or in patients with arthritis in which autoimmune phenomena have not been demonstrated. The entire PBA activity in rheumatoid arthritis patient serum was found associated with the macroglobulin fraction obtained by Sephadex G-200 chromatography and was precipitated by rabbit anti-human alpha 2-macroglobulin, but not by rabbit anti-Ig antibody. When alpha 2-macroglobulin was purified from patient serum the entire PBA activity was recovered in this fraction. Normal alpha 2-macroglobulin prepared by the same procedure had no PBA activity. Thus, the existence of a PBA associated with alpha 2-macroglobulin was demonstrated in serum of patients with rheumatoid arthritis.


Comparison of the effect of live Newcastle disease vaccine Clone 30 in broilers administered at day 1 or at day 7 and the effect of H120 vaccination at 17 days of age: a field experiment.
To analyse the results of a vaccination on the first day of age against Newcastle disease (ND) and on the 17th day of age against Infectious Bronchitis (IB) resp. with spray vaccines with Clone 30 and H120 vaccine. These vaccinations are compared in field circumstances with other vaccination methods. A serological examination and challenge test were used to be informed about the response and protection. From the present study the following conclusions can be drawn: Clear indications are obtained that following a spray vaccination against ND with Clone 30 vaccine of one-day-old broilers which possessed maternal antibodies, birds received a moderately good protection against ND, in spite of very low levels of HI antibodies. A spray vaccination against IB with H120 vaccine of broilers at 17 days of age gave some protection from two weeks after vaccination, however making a good conclusion about the protection is impossible and further investigation is required.


Effect of crosslink torsional stiffness on elastic behavior of semiflexible polymer networks.
Networks of semiflexible filaments are building blocks of different biological and structural materials such as cytoskeleton and extracellular matrix. The mechanical response of these systems when subjected to an applied strain at zero temperature is often investigated numerically using networks composed of filaments, which are either rigidly welded or pinned together at their crosslinks. In the latter, filaments during deformation are free to rotate about their crosslinks while the relative angles between filaments remain constant in the former. The behavior of crosslinks in actual semiflexible networks is different than these idealized models and there exists only partial constraint on torques at crosslinks. The present work develops a numerical model in which two intersecting filaments are connected to each other by torsional springs with arbitrary stiffness. We show that fiber networks composed of rigid and freely rotating crosslinks are the limiting case of the present model. Furthermore, we characterize the effects of stiffness of crosslinks on effective Young's modulus of semiflexible networks as a function of filament flexibility and crosslink density. The effective Young's modulus is determined as a function of the mechanical properties of crosslinks and is found to vanish for networks composed of very weak torsional springs. Independent of the stiffness of crosslinks, it is found that the effective Young's modulus is a function of fiber flexibility and crosslink density. In low density networks, filaments primarily bend and the effective Young's modulus is much lower than the affine estimate. With increasing filament bending stiffness and/or crosslink density, the mechanical behavior of the networks becomes more affine and the stretching of filaments depicts itself as the dominant mode of deformation. The torsional stiffness of the crosslinks significantly affects the effective Young's modulus of the semiflexible random fiber networks.


Peroxynitrite-modified DNA: a better antigen for systemic lupus erythematosus anti-DNA autoantibodies.
Native human DNA was modified by ONOO- (peroxynitrite), generated by the synergistic action of sodium nitroprusside [Na2Fe(CN)5NO], an NO donor, and pyrogallol, a superoxide donor. The modifications were analysed by UV absorption characteristics, fluorescence emission transitions, nuclease S1 digestibility and melting-temperature studies. Modified DNA was found to be highly immunogenic, inducing high-titre immunogen-specific antibodies in experimental animals. A maximum of 85% inhibition of the antibody binding was observed in competition ELISA with immunogen as inhibitor. SLE (systemic lupus erythematosus) anti-DNA autoantibodies recognized modified DNA as a better antigen than the native analogue. Modification of native DNA by ONOO-, forming neo-epitopes on the molecule, may be one of the factors for the induction of the autoimmune response seen in SLE.


Effect of a tunnel barrier on time delay statistics.
We develop a semiclassical approach for the statistics of the time delay in quantum chaotic systems in the presence of a tunnel barrier, for broken time-reversal symmetry. Results are obtained as asymptotic series in powers of the reflectivity of the barrier, with coefficients that are rational functions of the channel number. Exact expressions, valid for arbitrary reflectivity and channel number, are conjectured and numerically verified for specific families of statistical moments.


Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations.
Breast cancer patients frequently report hot flashes. Given that conventional hormone replacement therapy is generally contraindicated for them, other therapeutic modalities must be considered. The purpose of this review was to develop evidence-based recommendations on non-hormonal pharmacological interventions, including natural health products, for managing hot flashes in women undergoing treatment for breast cancer or with a history of breast cancer. A review of the scientific literature published between January 2000 and December 2011 was performed. A total of 26 randomized trials were identified. Studies showed that serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, antihypertensives and anticonvulsants significantly reduced the frequency and severity of hot flashes in breast cancer patients. Considering the evidence available to date, the CEPO recommends the following: (1) for breast cancer patients being treated with tamoxifen: (a) the use of venlafaxine, citalopram, clonidine, gabapentin and pregabalin be considered effective in treating hot flashes and (b) the use of paroxetine and fluoxetine be avoided, given that they may reduce the efficacy of tamoxifen; (2) for breast cancer patients not being treated with tamoxifen: (a) the use of venlafaxine, paroxetine, citalopram, clonidine, gabapentin and pregabalin be considered effective in treating hot flashes and (b) fluoxetine not be used to treat hot flashes, given that there is insufficient evidence for its therapeutic efficacy and (3) for breast cancer survivors, sertraline, phytoestrogens, black cohosh and St. John's wort not be used to treat hot flashes.


Anemia and iron status in the free-living and institutionalized elderly in Kentucky.
A study of the iron status and anemia in 101 elderly persons, age 60 to 95, included 50 free-living and 51 institutionalized subjects. Daily iron intakes and biochemical parameters including hemoglobin, hematocrit, mean corpuscular hemoglobin concentration (MCHC), plasma iron levels and total iron binding capacity (TIBC) were determined. In the free-living group, only 4% male and 8% female subjects had iron-deficiency anemia. Whereas about 40% of the institutionalized group had iron deficiency anemia with low hemoglobin, hematocrit, MCHC, plasma iron levels, and elevated TIBC. Hemoglobin, hematocrit, MCHC and plasma iron levels were significantly higher, and TIBC was significantly lower in the free-living group than the institutionalized group. The lack of correlation between dietary iron intakes and plasma iron levels suggest that iron deficiency anemia in these elderly subjects was not due to lack of iron intakes. The possible causes might be medications and diseases in these elderly subjects.


Expression of amelogenin and effects of cyclosporin A in developing hair follicles in rats.
Amelogenin, an enamel matrix protein has been considered to be exclusively expressed by ameloblasts during odontogenesis. However, burgeoning evidence indicates that amelogenin is also expressed in non-mineralizing tissues. Under the hypothesis that amelogenin may be a functional molecule in developing hair follicles which share developmental features with odontogenesis, this study for the first time elucidated the presence and functional changes of amelogenin and its receptors during rat hair follicle development. Amelogenin was specifically localized in the outer epithelial root sheath of hair follicles. Its expression appeared in the deeper portion of hair follicles, i.e. the bulbar and suprabulbar regions rather than the superficial region. Lamp-1, an amelogenin receptor, was localized in either follicular cells or outer epithelial sheath cells, reflecting functional changes during development. The expression of amelogenin splicing variants increased in a time-dependent manner during postnatal development of hair follicles. Amelogenin expression was increased by treatment with cyclosporin A, which is an inducer of anagen in the hair follicle, whereas the level of Lamp-1 and -2 was decreased by cyclosporin A treatment. These results suggest that amelogenin may be a functional molecule involved in the development of the hair follicle rather than an inert hair shaft matrix protein.


Efficacy and safety of hybrid endoscopic submucosal dissection compared with endoscopic submucosal dissection for rectal neuroendocrine tumors and risk factors associated with incomplete endoscopic resection.
Neuroendocrine tumors (NETs) are rising in prevalence, particularly with the rectal area. This study evaluated and compared the safety and effectiveness of hybrid endoscopic submucosal dissection (ESD) with those of ESD for rectal NETs and risk factors associated with incomplete endoscopic resection. A total of 272 consecutive patients who underwent ESD or hybrid ESD for rectal NETs at the Chinese PLA General Hospital in the period from February 2011 to September 2018 were involved in this study. Data were collected from clinical and endoscopic databases. The procedure time, en bloc resection, complete resection, complication, and recurrence rates were evaluated. In the hybrid ESD group were 111 patients (who had 119 lesions between them), with a further 161 patients (164 lesions) in the ESD group. No significance was found in baseline characteristics between the two groups. Hybrid ESD had a significantly shorter mean procedure time than ESD (13.2±8.3 vs. 18.1±9.7 min, P=0.000). Hybrid ESD showed similar en bloc resection (99.2% vs. 98.2%; P=0.373), complete resection (94.1% vs. 90.9%, P=0.641), and postprocedural bleeding (2.5% vs. 0.6%, P=0.313) rates to ESD. Univariate and multivariate analysis showed that higher histopathological grade was associated with incomplete resection. For rectal NET, both ESD and hybrid ESD are effective and safe forms of treatment. Hybrid ESD provides an alternative option in the treatment of rectal NETs. Further developments are needed to improve the complete resection rate, especially concerning tumors with higher histopathological grade.


Radiation therapy in paediatric gliomas: our institutional experience.
The aim of our retrospective study was to analyze the clinical outcome of paediatric glioma patients treated with radiation therapy (RT) in our institution. We retrieved the case records of all children with gliomas (age < 18 years) who received RT in our department between 2004 and 2007. We analyzed the information regarding patients' demography, clinical details, treatment given, RT details, and survival. The event-free survival (EFS), the period from the date of completion of RT to the date of the event, i.e. death/recurrence, was calculated with respect to age, sex, location of tumour (brainstem vs. non-brainstem), histopathology (low grade vs. high grade), extent of surgical resection, dose and duration of RT, and use of chemotherapy. A total of 70 children with glioma received RT during the above-mentioned period. The 3-year EFS rate for all patients was 44% and the median EFS period was 18 months. The 3-year EFS in patients who underwent surgical decompression and no surgery was 58% and 25%, respectively (p < 0.05). Patients with brainstem lesions had statistically significantly lower 3-year EFS to non-brainstem gliomas (28% vs. 56%, p < 0.01). Chemotherapy use showed no statistically significant trend towards better survival. RT is an effective modality of treatment in paediatric glioma patients in our setup. Early use of RT in incompletely resected low-grade gliomas is worth revisit-ing. Results of chemotherapy in high-grade glioma and brainstem gliomas are encouraging.


[Introduction of new prophylactic technologies at Nalchik health resort].
The introduction of educational programs on prevention of cardiovascular disorders at Nalchik health resort and the experience obtained show that correction of cardiovascular disease risk factors according to the educational programs consolidates positive results of complex sanatorium treatment, reduces risk factors level and promotes compliance of the patients to healthy life style.


Apical ballooning (takotsubo) syndrome with concurrent ST-segment elevation myocardial infarction.
We present the case of a 61-year-old woman admitted with chest pain and an ECG demonstrating ST-segment elevation in the lateral leads. Emergency coronary angiography demonstrated an occluded obtuse marginal branch. Percutaneous intervention was unsuccessful as the lesion could not be crossed with a wire. Left ventriculography and transthoracic echocardiography demonstrated hypokinesis of the entire apex but preserved contractility of the basal segments, consistent with a diagnosis of apical ballooning syndrome (ABS). Cardiac MRI demonstrated myocardial oedema in all mid to apical segments, with a left ventricular ejection fraction (LVEF) of 38%. Repeat study at 5 months demonstrated an infarct in the distribution of the occluded artery with late gadolinium enhancement, consistent with a diagnosis of a lateral wall myocardial infarction and an improvement in the LVEF to 51%. The case illustrates the novel observation that ABS and acute myocardial infarction may rarely occur simultaneously.


Randomised trial of two nicotine patch protocols distributed through a state quitline.
Most telephone quitlines provide free nicotine replacement therapy (NRT). An 8-week course is recommended, but few users complete it. Information is needed to help quitlines distribute NRT cost-effectively. Randomised two-group trial. Colorado QuitLine callers who smoked 16-20 cigarettes per day at enrolment and who were eligible for and agreed to receive free NRT. Provision of 4-week versus 8-week NRT supply; the 8-week supply was shipped in halves and required participants to request the second half (split-shipment protocol). Enrolment occurred during March 2010-February 2011, follow-up concluded in November 2011, and analysis was performed in 2012. Point abstinence (7 and 30 day) and prolonged abstinence (6 month) from tobacco use. Overall, 1495 study participants were enrolled and 57.7% completed follow-up. Abstinence rates did not differ significantly between study conditions: 13.8% versus 12.4% in 4-week versus 8-week arms, respectively, (30-day point abstinence, non-respondents treated as smokers). NRT duration was similar in both groups, due in part to purchase of additional patches in the 4-week group. About one-third of the 8-week group requested the full 8-week supply and had higher abstinence rates. Cost per quit was lower in the 4-week (compared to 8-week) group. A randomised trial did not find worse cessation outcomes among quitline users who received half the minimum recommended course of NRT, but offering the full recommended course using a split-shipment protocol may be reasonably cost-effective and supportive of NRT adherers. NCT01889771.


Essential oil of Eucalyptus gunnii hook. As a novel source of antioxidant, antimutagenic and antibacterial agents.
The present study describes radical scavenging capacity (RSC), antimutagenic and antibacterial properties of the essential oil (EO) of the leaves of Eucalyptus gunnii Hook. (Southern Montenegro). Chemical composition was evaluated by gas chromatography-mass spectrometry (GC-MS). In oil, 1,8-cineole (67.8%) and α-pinene (14.12%) were the major compounds comprising almost 82% of total EO. EO exhibited moderate DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity, with IC50 value of 7.19 µL/mL. The antimutagenic properties were assayed against the spontaneous and t-BOOH-induced mutagenesis in Escherichia coli IC202 oxyR mutant strain, deficient in removing radical oxygen species (ROS). Reduction of the spontaneous mutagenesis in the presence of E. gunnii EO was only slight, up to 12% at the highest concentration tested. However, when the oxidative mutagen was used, EO displayed more significant reduction of mutagenesis (maximum 23%) in a concentration dependent manner. Antibacterial activity was tested against the selected strains from ATTC and NCIB collections: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, Micrococcus flavus, Klebsiella pneumoniae, and the two Escherichia coli strains from our laboratory collection (SY252 and IB112) using both the disk-diffusion and MIC assays. The greatest sensitivity was shown by M. flavus, K. pneumoniae and E. coli lpcA (MIC = 0.83 mg/mL), while the highest resistance was shown by E. coli (ATTC 25922) and S. epidermidis. This study represents the first report on chemical composition and biological activity of the Eucalyptus gunnii in the South Balkan region and beyond.


Letter: influence of experimental parameters on identification of whole cell Rhizobium by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI ToF-MS) has been used to identify bacteria on the basis of its spectral nature. Identification of bacteria using MALDI ToF mass spectra depends on instrumental parameters and sample preparation protocol. Here we have optimized the sample preparation protocol for whole cell Rhizobium and evaluated the effect of its different growth phases to find out specific growth periods superior to the taxonomical approach. Sample preparation integrates the most important step influencing the quality and reproducibility of the spectra. The important factors in sample preparation include selection of matrix, solvent and acid concentration. A maximum numbers of peaks have been observed using 2,4- dihydroxy-phenylazobenzoic acid (HABA) rather than the commonly used alpha-cyano-4-hydroxy cinnamic acid (CHCA) or 3, 5-dimethoxy- 4-hydroxycinnamic acid (sinapinic acid) for whole cell Rhizobium identification. A protocol has been optimized after considering different experimental variables including various phases of bacterial growth and late log to stationary phase has been found to be best for identification of whole cell Rhizobium by this method.


Mobility assessments of geriatric emergency department patients: A systematic review.
We wished to determine the impact of emergency department (ED) mobility assessments for older patients on hospitalization, return visits, future falls, and frailty. We searched MEDLINE, Embase, CINAHL, Cochrane Library, PEDro, and OTseeker (September 2016). Two independent reviewers identified studies of patients ≥65 years with ED physical mobility assessments and outcomes of hospitalization, return to ED, falls, and frailty. Language was not restricted. Only clinical trials and observational studies were included. We identified 1,365 unique citations. Nine studies (six cohort and three cross-sectional) met full inclusion criteria. Patients (n=2,513) with mean age 75-85 years, admitted to hospital and discharged, underwent these ED evaluations: Timed Up and Go (TUG), Get Up and Go, tandem walk, and a gait assessment. Study quality was moderate to poor. Tandem walk did not predict falls at 90 days. TUG was not associated with return to the ED/hospitalization at 90 days. Get Up and Go was associated with hospital admission but not return to ED visits at 1 or 3 months. Due to clinical heterogeneity in study populations and outcomes, a meta-analysis was not undertaken. Despite multiple guidelines recommending a mobility assessment prior to ED discharge for older patients, we found that such assessments were neither associated with nor predictive of adverse outcomes. Robust research is required to guide clinicians on the utility of physical mobility assessments in older ED patients.


Eradicating catastrophic collapse in interdependent networks via reinforced nodes.
In interdependent networks, it is usually assumed, based on percolation theory, that nodes become nonfunctional if they lose connection to the network giant component. However, in reality, some nodes, equipped with alternative resources, together with their connected neighbors can still be functioning after disconnected from the giant component. Here, we propose and study a generalized percolation model that introduces a fraction of reinforced nodes in the interdependent networks that can function and support their neighborhood. We analyze, both analytically and via simulations, the order parameter-the functioning component-comprising both the giant component and smaller components that include at least one reinforced node. Remarkably, it is found that, for interdependent networks, we need to reinforce only a small fraction of nodes to prevent abrupt catastrophic collapses. Moreover, we find that the universal upper bound of this fraction is 0.1756 for two interdependent Erdős-Rényi (ER) networks: regular random (RR) networks and scale-free (SF) networks with large average degrees. We also generalize our theory to interdependent networks of networks (NONs). These findings might yield insight for designing resilient interdependent infrastructure networks.


Concurrent medical conditions among pregnant women - ignore at their peril: report from an antenatal anesthesia clinic.
Care of pregnant women with concurrent medical conditions can be optimized by multidisciplinary antenatal management. In the current study we describe women with concurrent medical conditions who attended our antenatal anesthesia clinic over a 14-year period, 2002-2015 and, based on the findings, we suggest new policies, strategies and practices to improve antenatal care. In 2002, an antenatal anesthesia clinic was established in Hadassah Medical Center. Each consultation focused on the concurrent medical condition. A written anesthesia strategy according to the medical condition and its anesthesia considerations was discussed and given to the patient. Data regarding clinic visits were recorded. A total of 451 clinic women attended the antenatal anesthesia clinic. Maternal age was 31.7 ± 6.0 years (mean ± SD), with gestational age of pregnancy 33.0 ± 5.4 weeks at the clinic visit. Musculoskeletal conditions (23% of all the women seen) were the most frequent concurrent conditions, followed by anesthesia related concerns 20%, neurologic conditions 19%, and cardiac conditions 15%. Women were provided plans that were deliberated carefully rather than being concocted during labor. A wide range of concurrent medical conditions was seen in the antenatal anesthesia clinic, however fewer women attended the clinic than expected according to known population frequencies of concurrent medical conditions. Women with concurrent medical conditions should have labor and anesthesia plans considered during the nine months of pregnancy, prior to delivery, and hospitals should have a means of obtaining this information in a timely manner. Finally, there is a need to develop additional antenatal anesthesia clinics.


Worst-case scenario analysis of physical demands in elite men handball players by playing position through big data analytics.
The physical demands of intermittent sports require a preparation based, by definition, on high-intensity actions and variable recovery periods. Innovative local positioning systems make it possible to track players during matches and collect their distance, speed, and acceleration data. The purpose of this study was to describe the worst-case scenarios of high-performance handball players within 5-minute periods and per playing position. The sample was composed of 180 players (27 goalkeepers, 44 wings, 56 backs, 23 centre backs and 30 line players) belonging to the first eight highest ranked teams participating in the European Men's Handball Championship held in January 2022. They were followed during the 28 matches they played through a local positioning system worn on their upper bodies. Total and high-speed distance covered (m), pace (m/min), player load (a.u.) and high-intensity accelerations and decelerations (n) were recorded for the twelve 5-min periods of each match. Data on full-time player average and peak demands were included in the analysis according to each playing position. A systematic three-phase analysis process was designed: 1) information capture of match activities and context through sensor networks, the LPS system, and WebScraping techniques; 2) information processing based on big data analytics; 3) extraction of results based on a descriptive analytics approach. The descriptive cross-sectional study of worst-case scenarios revealed an ~17% increment in total distance covered and pace, with a distinct ~51% spike in high-intensity actions. Significant differences between playing positions were found, with effect sizes ranging from moderate to very large (0.7-5.1). Line players, in particular, showed a lower running pace peak (~10 m/min) and wings ran longer distances at high speed (> 4.4 m/s) than the rest of the field players (~76 m). The worst-case scenario assessment of handball player locomotion demands will help handball coaches and physical trainers to design tasks that replicate these crucial match moments, thus improving performance based on a position-specific approach.


Blood flow velocity pattern of the anterior cerebral arteries. Before and after drainage of posthemorrhagic hydrocephalus in the newborn.
The blood flow velocity pattern of the anterior cerebral artery (ACA) was investigated using transcutaneous Doppler technique in ten preterm infants with posthemorrhagic hydrocephalus (PHH), before and after drainage of cerebrospinal fluid. The pulsatility index of the ACA was elevated during PHH, mainly due to an increase of peak systolic flow velocity, explained by an increased compliance of the vascular wall. The end diastolic flow velocity and the area under the velocity curve were not different before and after drainage, indicating that cerebrovascular resistance was not changed and blood flow through the ACA was not affected in the studied infants during PHH.


Vitiligo following a combined liver-kidney transplant.
We report an Afro-Caribbean male who developed vitiligo 10 days following a combined liver-kidney transplant from a Caucasian donor. Neither the donor nor the recipient had any previous history of vitiligo, nor of autoimmunity. The depigmentation gradually resolved by 8 weeks post-transplant with topical corticosteroids and standard maintenance immunosuppression. We propose that the skin depigmentation occurred due to the destruction of melanocytes by donor-derived alloreactive cytotoxic T-lymphocytes or antibody transferred during transplantation. Although vitiligo has been described in patients receiving allogeneic bone marrow transplantation for haematological malignancy, there are no previous reports of vitiligo post-solid organ transplantation.


Aldehyde dehydrogenase 2 (ALDH2) genotype affects rectal cancer susceptibility due to alcohol consumption.
Epidemiologic studies have shown the association between alcohol consumption and colorectal cancer, especially for rectal cancer. The alcohol related enzyme encoding gene ALDH2 has polymorphism Glu487Lys, and 487Lys allele is closely linked with phenotypic loss of enzyme activity. A hospital-based case-control study was conducted with 72 colon and 70 rectal cancer cases and 241 non-cancer controls to evaluate the alcohol consumption and ALDH2 Glu487Lys polymorphism. The logistic regression model was applied to estimate the odds ratios (ORs). The crude ORs for Glu/Lys and Lys/Lys genotype relative to Glu/Glu for colon and rectal cancer were not statistically significant. However, with the rectal cancer analysis, the ORs for high alcohol consumption were greater with 487Glu/Lys genotype compared with Glu/Glu, albeit not. These observations suggested rectal cancer risk might be influenced by ALDH2 gene polymorphism. The prevention effect by alcohol reduction might differ by ALDH2 genotype.


Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes.
The process of integrating the reverse-transcribed HIV-1 DNA into the host chromosomal DNA is catalyzed by the virally encoded enzyme integrase (IN). Integration requires two metal-dependent reactions, 3' end processing and strand transfer. Compounds that contain a diketo acid moiety have been shown to selectively inhibit the strand transfer reaction of IN in vitro and in infected cells and are effective as inhibitors of HIV-1 replication. To characterize the molecular basis of inhibition, we used functional assays and binding assays to evaluate a series of structurally related analogs. These studies focused on investigating the role of the conserved carboxylate and metal binding. We demonstrate that an acidic moiety such as a carboxylate or isosteric heterocycle is not required for binding to the enzyme complex but is essential for inhibition and confers distinct metal-dependent properties on the inhibitor. Binding requires divalent metal and resistance is metal dependent with active site mutants displaying resistance only when the enzymes are evaluated in the context of Mg(2+). The mechanism of action of these inhibitors is therefore likely a consequence of the interaction between the acid moiety and metal ion(s) in the IN active site, resulting in a functional sequestration of the critical metal cofactor(s). These studies thus have implications for modeling active site inhibitors of IN, designing and evaluating analogs with improved efficacy, and identifying inhibitors of other metal-dependent phosphotransferases.


Utility of endoscopic ultrasound in the diagnosis of aberrant right subclavian artery.
Aberrant right subclavian artery (ARSA) is the most common congenital anomaly of the aortic arch occurring in 0.4-2.0% of the general population. Instead of arising from the brachiocephalic artery, the ARSA arises as the last branch from the aortic arch. The aim of this study was to determine the prevalence of ARSA in patients undergoing upper endoscopic ultrasound (EUS) and to describe the EUS characteristics of ARSA. A retrospective review was conducted of 7513 upper EUS exams performed from 1 July 2000 to 1 February 2005. In total, 27 (0.36%, 95% CI 0.22-0.50%) of 7513 patients undergoing upper EUS were found to have an ARSA (10 male, 17 female; mean age 58 years, range 23-81 years). Of the 27 patients, 16 had only radial EUS, 10 had radial and linear EUS, and one had only linear EUS. In all 26 patients who underwent radial imaging, a well-defined, anechoic tubular structure was seen originating from the aortic arch and passing between the esophagus and spine. In all 11 patients undergoing linear imaging, the abnormal anatomy was detected and the vascular nature confirmed by Doppler. In one patient, both radial and linear imaging identified unsuspected aneurismal dilatation of the ARSA; a rare condition referred to as Kommerell's diverticulum (KD). None of the other 26 patients had symptoms to suggest an ARSA. Of the 14 patients who had computed tomography (CT) prior to EUS, only four were initially reported to have ARSA. However, later review of the CT scans verified an ARSA in all 14 patients. Of the two patients who underwent a barium swallow, only one had findings suggestive of ARSA. This report highlights the utility of both radial and linear EUS imaging in identifying previously unsuspected ARSA and associated anomalies. This report also suggests the need for careful review of the CT in patients suspected of having ARSA due to the frequent failure of radiologists to identify, or report, this anomaly when particular focus is not given.


Evidence for the maintenance of motoneurone properties by muscle activity.
1. Electrophysiological properties of soleus motoneurones in adult cats were examined with intracellular electrodes following alterations of activity of the soleus muscle induced by transection of the thoracic spinal cord or by conduction block of the muscle nerve with tetrodotoxin (TTX) cuffs. Attempts were also made to maintain muscle activity by daily stimulation of the maintain muscle activity by daily stimulation of the peripheral nerve. 2. Within 8 days after transection of the thoracic cord, soleus motoneurones showed a significant decrease in the duration of afterhyperpolarization following action potentials. This change in motoneurone properties induced by cord transection was prevented by daily stimulation of the sciatic nerve. 3. Soleus motoneurones showed a significant decrease in the duration of after-hyperpolarization within 8 days after conduction block of the soleus nerve with TTX. This change in montoneurone properties was prevented by daily stimulation of the nerve peripheral to the TTX cuff but not central to the cuff. 4. The soleus muscle showed a significant decrease in weight relative to body weight within 8 days after transection of the thoracic cord. This decrease in muscle weight following cord transection was prevented by daily stimulation of the sciatic nerve. 5. No fibrillation was detected in the soleus muscle 8 days after conduction block of the soleus nerve with TTX. The maximum twitch tension of the soleus muscle evoked by nerve stimulation showed no significant difference between the two sides treated and untreated with TTX. Fast axoplasmic transport measured with cholinesterase as a marker was not affected by TTX. Thus, there was no sign of functional although morphological abnormalities were found in some nerve fibres. 6. It is concluded that motoneurone properties in an adult depend partly upon some factors associated with activity of the innervated muscles and that such trophic signals are retrogradely carried by the motor axons.


c-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells.
To further characterize the role of hepatocyte growth factor-scatter factor (HGF-SF) and its receptor (c-Met) in osteosarcoma (OS), human OS cell lines with low (SAOS-2) and high (SAOS-LM2) metastatic potential, and cell lines derived from spontaneous canine OS were studied. All cell lines were evaluated for c-Met and HGF-SF expression and receptor activation using Northern, RT-PCR, and Western blot analyses, respectively. Functional activity of receptor-ligand interaction was measured using c-Met phosphorylation status, proliferation assays (anchorage-dependent and -independent), Matrigel invasion, modulation of urokinase plasminogen activator (uPA) expression, and cell dispersion (scattering). All cell lines exhibited steady-state mRNA expression of c-Met. The canine OS cell lines also expressed HGF-SF mRNA as determined by RT-PCR analysis. Western analysis showed c-Met protein expression and HGF-stimulated (human) or constitutive (canine) receptor autophosphorylation. Treatment with recombinant human HGF resulted in enhanced proliferation in 3 of 5 OS cell lines and enhanced colony formation in 2 of 5 OS cell lines. Matrigel invasion was significantly enhanced in 3 of the cell lines and uPA levels were significantly increased in the SAOS-2 cells following HGF treatment. Scattering was enhanced in both the SAOS-2 and SAOS-LM2 cells. These data support the involvement of c-Met and HGF-SF in the growth and progression of human and canine OS, and may offer new targets for the development of therapeutic strategies for OS.


Termination of tolerance to human gamma globulin in mice by antigen and bacterial lipopolysaccharide (endotoxin).
Bacterial lipopolysaccharides (endotoxin) allowed the circumvention of the thymus-derived (T) cell helper function otherwise required for the antibody response in mice to human gamma globulin (HGG). In an analogous fashion, the state of tolerance to HGG, existing at a time when bone marrow-derived (B) cells had lost their unresponsiveness, could be terminated by the injection of both immunogenic HGG and endotoxin, but by neither given alone. However, no effect on tolerance to HGG could be observed when this regimen was followed at a time when B cells were tolerant. After the spontaneous recovery from tolerance in B cells, it seemed that specific priming was occurring in that population. This phenomenon was observed either by the injection of endotoxin and HGG or by the adoptive transfer of cells into irradiated hosts. These data have been discussed in the light of potential autoimmune manifestations that could theoretically follow a simultaneous gram-negative bacterial infection along with a release of self-antigen.


Synthesis of a cyclic peptide containing norlanthionine: effect of the thioether bridge on peptide conformation.
Two diastereomeric analogues of ring C of nisin incorporating a novel norlanthionine residue have been synthesized via a triply orthogonal protecting group strategy. A full structural study was carried out by NMR, which elucidated the conformational properties of the two peptides and enabled the identity of each diastereoisomer to be proposed.


Crocacin, a new electron transport inhibitor from Chondromyces crocatus (myxobacteria). Production, isolation, physico-chemical and biological properties.
Crocacin was isolated from the biomass of the myxobacterium Chondromyces crocatus, strain Cm c3. It inhibited the growth of a few Gram-positive bacteria and a wide spectrum of yeasts and molds. In beef heart submitochondrial particles, crocacin blocked the electron transport within the bc1-segment (complex III) and caused a red shift in the reduced spectrum of cytochrome b with a maximum at 569 nm.


Increased sensitivity of an enzyme immunoassay for human interferon alpha 1 using a mixture of three monoclonal antibodies.
A sensitive sandwich ELISA for the quantification of human interferon (IFN)-alpha 1 was designed. The assay employed IFN-alpha 1- specific polyclonal antibody for coating and monoclonal antibodies (mAbs) to IFN-alpha 1 as a second antibody. A major increase in sensitivity of the assay could be achieved, when polyclonal antibody was combined with a mixture of three mAbs binding to different regions of IFN-alpha 1, compared to the combination of a polyclonal antibody with a single mAb. The sensitivity of the established ELISA was close to that of an antiviral IFN-bioassay. The ELISA did not cross-react with IFN-alpha 2, beta, tau or omega. The immunoassay allowed to estimate the content of IFN-alpha 1 in leukocyte IFN-alpha to about 25-50% or to 2-6% in Namalwa IFN-alpha, respectively.


Trauma-Informed Care for Youth in Foster Care.
For decades, evidence has shown an undeniable connection between childhood trauma and chronic adverse reactions across the lifespan (Bilchik & Nash, 2008; Perry, 2001; Perry, 2006). Childhood traumatic experiences are associated with serious and persistent, long-term physical, psychological, and substance abuse issues. In addition to adverse effects on physical health, research indicates that early childhood trauma has particularly adverse effects on adolescent self-esteem, coping skills, school performance, self-regulation, critical thinking, self-motivation, and the ability to build healthy relationships (O'Connell, Boat, & Warner, 2009). A traumatic event is a dangerous or distressing experience, outside the range of usual human experience that overwhelms the capacity to cope and frequently results in intense emotional and physical reactions, feelings of helplessness and terror, and threatens serious injury or death (The National Child Traumatic Stress Network [NCTSNET], 2014). Approximately five million children each year in the United States experience some type of traumatic experience (Perry, 2006). Nationwide community studies estimate between 25% and 61% of children and adolescents have a history of at least one exposure to a potentially traumatic event and 38.5% of American adults claim to have experienced at least one traumatic event before the age of 13 (Briggs et al., 2012; Gerson & Rappaport, 2013). According to results of a 2002-2003 survey of 900 New York City adolescents, 24% reported a history of witnessing someone being shot, 12% reported exposure to someone being killed, and 51% reported witnessing someone being beaten or mugged (O'Connell et al., 2009). Each year, 2-3 million children are victims of maltreatment, a type of trauma, including physical and/or sexual abuse (U.S. Department of Health and Human Services, 2014; Perry, 2006). Compared to the general population, youth in foster care are significantly more likely to have experienced violence, specifically abuse and/or neglect (Burns et al., 2004). It is estimated that approximately 90-percent of children in foster care have experienced a traumatic event, with nearly half reporting exposure to four or more types of traumatic events (Stein et al., 2001). Given the widespread prevalence of traumatic exposures, it is important for the mental health professionals working with foster care youth, to be aware of the prevalence and various types of trauma that are most common. Focus in treatment is typically on behavioral and emotional reactions rather than addressing the context of these symptoms, including trauma exposure histories and trauma-specific reactions. Clinicians must maintain awareness of the frequency and impact of childhood traumatic experiences on subsequent behaviors and overall functioning. Clinicians should appreciate the link between how traumatized children understand the world and interact with others differently from other children and how to provide appropriate treatment for children with a history of traumatic exposures. Practitioners must remain alert to symptoms that may suggest a history of trauma and must have an understanding of the difficulties adolescents may face regulating their emotions and behavior, as a symptom of a past traumatic experience. The failure to address trauma through screening, assessment, and treatment has major implications for long-term public health costs and services.


[Hepatitis A: antibody conversion under gamma globulin (author's transl)].
55 soldiers of the Austrian UNO contingent to the Near East, stationed on the Golan Heights for 6 months were examined before and after their period of duty for hepatitis A antibodies and the liver specific enzymes GOT, GTP and gamma-GT were determined. All received prophylactic gamma globulin to prevent infectious hepatitis at a dosage of 0.05 ml/kg body weight before flying out and after three months. No cases of hepatitis occurred, but 4 sero-negative subjects displayed antibody conversion. No concomitant changes in the liver enzyme values were recorded, however. These findings are discussed.