Modified technique of BMV for severe submitral stenosis.
We present a case where difficulty was encountered during balloon mitral valvotomy (BMV) because of severe submitral stenosis. As the orifice was 0.4 cm² at submitral level the BMV balloon catheter could not enter the left ventricle. We used a modified technique of liberating the submitral apparatus that facilitated successful BMV.


Effects of both a melatonin agonist and antagonist on seasonal changes in body mass and energy intake in the garden dormouse.
Many physiological functions including nycthemeral rhythm, reproductive cycles, body temperature and body mass are controlled by photoperiodic changes in different species. In the hibernating garden dormouse, both energy intake and body mass increase with the duration of the night. This seasonal mass gain is spontaneous and reversible. We have studied the occurrence of the increase of body mass by taking into account the endogenous variations of melatonin due to changing photoperiod or to pharmacological treatment. A single daily administration of either a melatonin agonist or antagonist just before night mimics the short day and long day effects, respectively. Compared to the control animals (natural photoperiod), the mass gain was greater and occurred earlier in animals under short days (6 h light (L)/18 h dark (D)) and in those receiving the melatonin agonist (S 20304). The animals treated with the antagonist (S 20928) during the same period exhibited no mass gain and their response was similar to that of the long-day group (16L/8D). Solely agonist treatment acted on metabolic rate. These results demonstrate that the duration of melatonin-receptor exposure per day determines the onset of seasonal obesity in garden dormice and, on the other hand, that restriction of melatonin-receptor exposure by pharmacological treatment prevents it.


Paralumbar muscle activity in chronic low back pain.
Muscle spasm is often considered to be a prominent feature operating in chronic low back spin syndrome (LBP). The present study compared levels of paralumbar muscle activity, determined by an electromyogram (EMG), for LBP patients and normal subjects during periods of rest and voluntary muscular contraction. The resting state EMG measure did not differ in the 2 groups. However, when attempting to relax the low back while contracting other muscle groups, LBP patients exhibited higher mean levels of low back muscle activity as compared to the non-pain group. These results would suggest that such "cocontraction relaxation" procedures may provide a viable behavioral technique for assessing and possibly treating functional backache thought to be symptomatic of muscle spasm. Previous studies employing feedback and progressive relaxation techniques have trained subjects to reduce muscle tension in the resting state. Results of the present study suggest that the acquisition of "resting level" relaxation may be of little benefit to patients who exhibit excessive muscular tension while performing daily tasks. Rather, to maximize the likelihood of beneficial results, training would be better directed at relaxation of the low back during activity of other muscle groups.


Mechanisms of capsaicin- and lactic acid-induced bronchoconstriction in the newborn dog.
1. Capsaicin activation of the pulmonary C fibre vanilloid receptor (VR1) evokes the pulmonary chemoreflex and reflex bronchoconstriction. Among potential endogenous ligands of C fibre afferents, lactic acid has been suggested as a promising candidate. We tested the hypotheses that (a) lactic acid behaves as a stimulant of C fibre receptors in the newborn dog to cause reflex bronchoconstriction, and (b) lactic acid causes reflex bronchoconstriction via the same pulmonary C fibre receptor mechanism as capsaicin using the competitive capsaicin/VR1 receptor antagonist capsazepine. 2. Right heart injection of lactic acid caused a significant increase (47 +/- 8.0 %) in lung resistance (RL) that was atropine sensitive (reduced by 75 %; P < 0.05), consistent with reflex activation of muscarinic efferents by stimulation of C fibre afferents. 3. Infusion of the competitive capsaicin antagonist capsazepine caused an 80 % reduction (P < 0.01) in the control bronchoconstrictor response (41 +/- 8.5 % increase in RL) to right heart injections of capsaicin. The effects of capsazepine are consistent with reversible blockade of the VR1 receptor to abolish C fibre-mediated reflex bronchoconstriction. 4. Lactic acid-evoked increases in RL were unaffected by VR1 blockade with capsazepine, consistent with a separate lactic acid-induced reflex mechanism. 5. We conclude that (a) putative stimulation of C fibres with lactic acid causes reflex bronchoconstriction in the newborn dog, (b) capsazepine reversibly antagonizes reflex bronchoconstriction elicited by right heart injection of capsaicin, presumably by attenuating capsaicin-induced activation of the C fibre 'capsaicin' receptor (VR1), and (c) capsazepine resistance of lactic acid-induced bronchoconstriction indicates that lactic acid evokes reflex bronchoconstriction by a separate mechanism, possibly via the acid-sensing ionic channel.


Real-time detection of somatic hybrid cells during electrofusion of carrot protoplasts with stably labelled mitochondria.
Somatic hybridisation in the carrot, as in other plant species, enables the development of novel plants with unique characteristics. This process can be induced by the application of electric current to isolated protoplasts, but such electrofusion requires an effective hybrid cell identification method. This paper describes the non-toxic fluorescent protein (FP) tagging of protoplasts which allows discrimination of fusion components and identification of hybrids in real-time during electrofusion. One of four FPs: cyan (eCFP), green (sGFP), yellow (eYFP) or the mCherry variant of red FP (RFP), with a fused mitochondrial targeting sequence, was introduced to carrot cell lines of three varieties using Agrobacterium-mediated transformation. After selection, a set of carrot callus lines with either GFP, YFP or RFP-labelled mitochondria that showed stable fluorescence served as protoplast sources. Various combinations of direct current (DC) parameters on protoplast integrity and their ability to form hybrid cells were assessed during electrofusion. The protoplast response and hybrid cell formation depended on DC voltage and pulse time, and varied among protoplast sources. Heterofusants (GFP + RFP or YFP + RFP) were identified by detection of a dual-colour fluorescence. This approach enabled, for the first time, a comprehensive assessment of the carrot protoplast response to the applied electric field conditions as well as identification of the DC parameters suitable for hybrid formation, and an estimation of the electrofusion success rate by performing real-time observations of protoplast fluorescence.


First data on the structure of tubes formed by phoronids.
Phoronids are marine benthic animals that live in tubes in soft sediment or hard substrata; the phoronids form the tubes by digging or boring. Epidermal glands produce much of the material of the tube, which is completely imbedded in the soft sediment or hard substrata. The structure of phoronid tubes has not been previously studied in detail. In the current research, the morphology and microstructure of the tubes were studied by light microscopy, histology, and scanning electron microscopy for the following species: Phoronis ijimai, Phoronis svetlanae, Phoronis hipporcrepia, Phoronis australis, and Phoronopsis harmeri. In most of these species, the tube consists of an inner organic cylinder and an external layer. The inner organic cylinder is formed by three layers (inner, middle, and outer) of thin films. Each film is formed by fibers, whose thickness differs in different species. These fibers form a net, whose density is higher in digging phoronids than in boring phoronids. The middle layer is formed by highly compressed thin films. The outer layer is the densest portion of the inner cylinder and is associated with the external layer. The external layer is absent in some species (P. australis) but is well developed in digging phoronids. The differences in the organization of tube are consistent with the biology of each species and depend on the type of substrata and on the life style of the animal. Tube organization substantially differs between phoronids and sedentary annelids: the inner organic cylinder is much thicker in phoronid than in annelid tubes, and the fibers that form films are randomly oriented in phoronids but regularly oriented in annelids. In annelids but not in phoronids, inorganic particles in the external layer are usually surrounded and glued together by organic material. These differences may be used to distinguish phoronid tubes from annelid tubes in present-day benthic samples and also in fossil samples.


Phylogenetic analysis of different breeds of domestic chickens in selected area of Peninsular Malaysia inferred from partial cytochrome b gene information and RAPD markers.
The present investigation was carried out in an attempt to study the phylogenetic analysis of different breeds of domestic chickens in Peninsular Malaysia inferred from partial cytochrome b gene information and random amplified polymorphic DNA (RAPD) markers. Phylogenetic analysis using both neighbor-joining (NJ) and maximum parsimony (MP) methods produced three clusters that encompassed Type-I village chickens, the red jungle fowl subspecies and the Japanese Chunky broilers. The phylogenetic analysis also revealed that majority of the Malaysian commercial chickens were randomly assembled with the Type-II village chickens. In RAPD assay, phylogenetic analysis using neighbor-joining produced six clusters that were completely distinguished based on the locality of chickens. High levels of genetic variations were observed among the village chickens, the commercial broilers, and between the commercial broilers and layer chickens. In this study, it was found that Type-I village chickens could be distinguished from the commercial chickens and Type-II village chickens at the position of the 27th nucleotide of the 351 bp cytochrome b gene. This study also revealed that RAPD markers were unable to differentiate the type of chickens, but it showed the effectiveness of RAPD in evaluating the genetic variation and the genetic relationships between chicken lines and populations.


New concepts in the treatment of rheumatoid arthritis.
Recent advances have made rheumatoid arthritis (RA) amenable to treatment. Clinical studies in patients with early and established RA have broadened understanding of its pathogenesis and have fundamentally changed the therapeutic approach to this disease. Quantum leaps in therapy-including the use of early, aggressive therapy, combination therapy, and the introduction of anti-cytokine agents-have improved patients' quality of life, eased clinical symptoms, retarded the progression of joint destruction, and delayed disability. We review clinical evidence supporting these therapeutic approaches. Diagnostic and therapeutic challenges are highlighted, and a decision tree to guide treatment in patients with early or established RA is provided.


Internet of Things for Mental Health: Open Issues in Data Acquisition, Self-Organization, Service Level Agreement, and Identity Management.
The increase of mental illness cases around the world can be described as an urgent and serious global health threat. Around 500 million people suffer from mental disorders, among which depression, schizophrenia, and dementia are the most prevalent. Revolutionary technological paradigms such as the Internet of Things (IoT) provide us with new capabilities to detect, assess, and care for patients early. This paper comprehensively survey works done at the intersection between IoT and mental health disorders. We evaluate multiple computational platforms, methods and devices, as well as study results and potential open issues for the effective use of IoT systems in mental health. We particularly elaborate on relevant open challenges in the use of existing IoT solutions for mental health care, which can be relevant given the potential impairments in some mental health patients such as data acquisition issues, lack of self-organization of devices and service level agreement, and security, privacy and consent issues, among others. We aim at opening the conversation for future research in this rather emerging area by outlining possible new paths based on the results and conclusions of this work.


Link atom bond length effect in ONIOM excited state calculations.
We investigate how the choice of the link atom bond length affects an electronic transition energy calculation with the so-called our own N-layer integrated molecular orbital molecular mechanics (ONIOM) hybrid method. This follows our previous paper [M. Caricato et al., J. Chem. Phys. 131, 134105 (2009)], where we showed that ONIOM is able to accurately approximate electronic transition energies computed at a high level of theory such as the equation of motion coupled cluster singles and doubles (EOM-CCSD) method. In this study we show that the same guidelines used in ONIOM ground state calculations can also be followed in excited state calculations, and that the link atom bond length has little effect on the ONIOM energy when a sensible model system is chosen. We also suggest further guidelines for excited state calculations which can help in checking the effectiveness of the definition of the model system and controlling the noise in the calculation.


The assessment of Proteus mirabilis susceptibility to ceftazidime and ciprofloxacin and the impact of these antibiotics at subinhibitory concentrations on Proteus mirabilis biofilms.
Rods of the Proteus genus are commonly isolated from patients, especially from the urinary tracts of the catheterised patients. The infections associated with biomaterials are crucial therapeutic obstacles, due to the bactericidal resistance of the biofilm. The aim of this study was to assess the susceptibility of P. mirabilis planktonic forms to ciprofloxacin and ceftazidime, the ability to form biofilm, and the impact of chosen sub-MIC concentrations of these antibiotics on biofilm at different stages of its formation. The research included 50 P. mirabilis strains isolated from wounds and the urinary tracts from patients of the University Hospital No. 1 in Bydgoszcz. The assessment of susceptibility to ciprofloxacin and ceftazidime was conducted using micromethods. The impact of sub-MIC concentrations of the chosen antibiotics on the biofilm was measured using the TTC method. The resistance to ciprofloxacin was confirmed for 20 strains (40.0%) while to ceftazidime for 32 (64.0%) of the tested P. mirabilis strains. All of the tested strains formed biofilm: 24.0% weakly, 26.0% moderately, and 50.0% strongly. It was determined that ciprofloxacin and ceftazidime caused eradication of the biofilm. Moreover, the connection between origin of the strains, biofilm maturity level, and resistance to antibiotics was proved.


HER2 status in pure ductal carcinoma in situ and in the intraductal and invasive components of invasive ductal carcinoma determined by fluorescence in situ hybridization and immunohistochemistry.
To determine the HER2 status of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. The increased prevalence of HER2 amplification and overexpression in DCIS is considered to be maintained in the intraductal component of IDC; however, HER2 amplification and overexpression are detected much less in IDC. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed to detect HER2 in 270 IDCs with an intraductal component and in 50 pure DCIS samples; IHC was also performed in 116 metastatic nodes. HER2 was found to be amplified in 77 cases (28.5%) and overexpressed in 79 (29.3%) of the 270 IDCs. HER2 amplification was similar between intraductal and invasive components of the same tumour. The concordance for HER2 status between invasive and intraductal components of individual tumours was 98.5% and 99.3% by FISH and IHC, respectively. HER2 was amplified in 25 (50%) of the 50 pure DCIS samples. HER2 overexpression in metastatic nodes resembled the HER2 status in the primary tumour for 108 (93.1%) of 116 cases (kappa =0.831). Our study indicates that the intraductal component of IDC may differ biologically when compared with pure DCIS. HER2 appears to lack a critical role in the progression from DCIS to IDC and HER2 status is maintained in metastatic lesions.


Induction of protective immunity to Theileria annulata using two major merozoite surface antigens presented by different delivery systems.
Allelic forms (Tams1-1 and Tams1-2) of the major merozoite surface antigen gene of Theileria annulata have recently been expressed in Escherichia coli and in Salmonella typhimurium aroA vaccine strain SL3261. To test the potential of subunit vaccines against T. annulata infection, we immunized four groups of three calves with either recombinant (re-) (Tams1-1 and Tams1-2) proteins or naked DNA encoding these antigens. Group I was immunized intramuscularly with both re-proteins incorporated into immunostimulating complexes (ISCOMs). Group II was inoculated intramuscularly with naked plasmid DNA encoding Tams1-1 and Tams1-2. Groups III and IV received S. typhimurium SL3261 [pSTams1-1][pIP5] and SL3261 [pSTams1-2] [pIP5] subcutaneously and orally, respectively. A final group of three animals (Group V) served as an unimmunized control group. Four weeks after the last immunization all calves were challenged with a T. annulata stabilate generated from blood of an infected animal with 30% piroplasm parasitaemia. All calves vaccinated with ISCOMs proved to be protected from T. annulata infection and had generated antibodies against both re-(Tams1-1 and Tams1-2) at the time of challenge. In two of these animals the antibody had a surface binding profile by IFAT. Two of three calves immunized with naked DNA also proved to be protected, but none of the animals had generated any detectable antibodies against the recombinants. Salmonella-based delivery of the recombinants did not induce any protection; two of six animals died of theileriosis and there was no difference between subcutaneous or oral administration. These preliminary results show that re-(Tams1-1 and/or Tams1-2) may elicit protective immune responses in cattle, depending on the antigen delivery system.


Regulatory triangle of neurodegeneration, adult neurogenesis and microRNAs.
MicroRNAs (miRNAs) have emerged as a new class of RNA molecules which are short in length, less in number but play bigger role in regulation of cellular events. miRNAs keep cellular homeostasis in tight control by fine tuning expression of protein coding genes at post-transcriptional level. Neurogenesis and neurodegeneration are two complex processes which are regulated by dynamic expression of regulatory proteins like transcription factors and signaling proteins. Evidences are accumulating that expression of miRNAs play major role in fate determination of neuronal cells undergoing neurogenesis or neurodegeneration. Neurodegeneration either induced by genetic factors or environmental chemicals results in development of neurodegenerative disorders like Parkinson's or Alzheimer's. With increasing acceptance of adult neurogenesis, it seems possible that inducing neurogenesis in adult brain can help in fighting with neurodegenerative disorders. Regulatory RNA molecules, like miRNAs are presenting them as potential therapeutic targets for inducing neurogenesis and controlling neurodegeneration. In the current review, we are exploring the link between neurodegeneration and adult neurogenesis regulation by focusing on miRNAs.


Targeting RSK2 in human malignancies.
p90 ribosomal S6 kinase 2 (RSK2) belongs to a Ser/Thr kinase family containing four members, RSK1 - 4, which play an essential role in a number of cellular functions including cell cycle, survival and proliferation. Recent advances reveal a crucial role of RSK2 in oncogenesis and tumor progression, making RSK2 an attractive therapeutic target for cancer treatment. Recent findings identifying the role of RSK2 in human cancers, including hematopoietic malignancies and solid tumors. Therapeutic implications of targeting RSK2 are also discussed with regard to clinical circumstance. A better understanding of molecular mechanisms underlying RSK2 activation and its contribution to human cancers and also insight into the development of novel targeted cancer therapy. The significance of RSK2 in cancer cell survival, proliferation, invasion and tumor metastasis varies amongst human malignancies and depends on the signaling properties of the oncogenes and cellular microenvironment of the transformed cells. Thus, further exploitation of RSK2 signaling and its dynamic interaction with other crucial oncogenic and pro-metastatic pathways in different human malignancies is needed for more effective therapeutic interventions.


Molecular cloning and evolutionary analysis of the GJA1 (connexin43) gene from bats (Chiroptera).
Gap junction protein connexin43 (Cx43), encoded by the GJA1 gene, is the most abundant connexin in the cardiovascular system and was reported as a crucial factor maintaining cardiac electrical conduction, as well as having a very important function in facilitating the recycling of potassium ions from hair cells in the cochlea back into the cochlear endolymph during auditory transduction processes. In mammals, bats are the only taxon possessing powered flight, placing exceptional demand on many organismal processes. To meet the demands of flying, the hearts of bats show many specialties. Moreover, ultrasonic echolocation allows bat species to orientate and often detect and locate food in darkness. In this study, we cloned the full-length coding region of GJA1 gene from 12 different species of bats and obtained orthologous sequences from other mammals. We used the maximum likelihood method to analyse the evolution of GJA1 gene in mammals and the lineage of bats. Our results showed this gene is much conserved in mammals, as well as in bats' lineage. Compared with other mammals, we found one private amino acid substitution shared by bats, which is located on the inner loop domain, as well as some species-specific amino acid substitutions. The evolution rate analyses showed the signature of purifying selection on not only different classification level lineages but also the different domains and amino acid residue sites of this gene. Also, we suggested that GJA1 gene could be used as a good molecular marker to do the phylogenetic reconstruction.


Developmental profile and tissue distribution of Drosophila alcohol dehydrogenase: an immunochemical analysis with monoclonal antibodies.
To analyze Drosophila alcohol dehydrogenase gene (Adh) expression and tissue distribution at various developmental stages, we devised several immunochemical techniques making use of monoclonal antibodies against Drosophila alcohol dehydrogenase (ADH), which had been obtained previously. We here report their application to analyze the expression of Adh in a wild-type strain of D. melanogaster. s-ELISA tests were performed to evaluate fluctuations in ADH content and specific activity during development in individual organs as well as in whole individuals. In all cases, ADH specific activity appeared to be quite constant, which implies that variations in enzyme activity reflect differences in protein content. Immunoblottings of crude homogenates revealed immunoreactive low relative molecular mass peptides in addition to the 27 KD monomeric band, showing a conserved banding pattern in different organs and developmental stages. Immunohistochemical assays on whole organs were used to analyze the general pattern of ADH distribution. Immunoperoxidase staining of cryosections proved to be of crucial relevance, as it yielded full details of the tissue localization of ADH within the ADH-positive organs. We have shown not only that ADH displays a specific distribution in some organs but also that the enzyme is restricted to certain cell types.


Prevalence and impact of body physical changes in HIV patients treated with highly active antiretroviral therapy: results from a study on patient and physician perceptions.
Patients infected with HIV treated with highly active antiretroviral therapy (HAART) frequently develop body physical changes (BPC) that have an important psychosocial burden. The purpose of this study was to determine the prevalence of BPC observed by HIV-infected patients and their attending physicians and to assess the impact BPC had on daily life. In this epidemiologic multicenter study, patients with HIV infection and their treating physicians filled out parallel questionnaires about their perceptions of specific BPC and their impact on daily activities. A total of 965 patient-physician questionnaires were collected across 98 health centers. Patient's mean age was 43.7 +/- 8.5 years and 72.6% were men. Adjusted prevalence of perceived BPC by patients and physicians was 55.1% (95% confidence interval [CI]: 52.0-58.1) and 55.2% (95% CI: 52.1-58.2), respectively (p = 1.000). Overall patient-physician agreement concerning perception of BPC was 83% (p < 0.0005). The most common BPC was lipoatrophy, described by 46.8% (95% CI: 43.7-49.8) of patients and 49.4% (95% CI: 46.3-52.5) of physicians (p = 0.033) followed by lipohypertrophy. No gender differences were observed in the global prevalence of BPC (p = 0.649). However, significantly more women reported lipoatrophy of the lower limbs (p = 0.009) and buttocks (p = 0.007), as well as lipohypertrophy (p = 0.007), than men; 58.2% (95% CI: 54.0-62.4) patients noted that BPC negatively affected their daily activities. This study reflects the high prevalence of patient and physician-perceived BPC in the HIV population, and the adverse impact on daily life. Physicians should be aware of the psychosocial consequences of BPC in HIV patients in order to improve patient well-being.


Doxorubicin-induced senescence promotes stemness and tumorigenicity in EpCAM-/CD133- nonstem cell population in hepatocellular carcinoma cell line, HuH-7.
The therapeutic induction of senescence is a potential means to treat cancer, primarily acting through the induction of a persistent growth-arrested state in tumors. However, recent studies have indicated that therapy-induced senescence (TIS) in tumor cells allows for the prolonged survival of a subgroup of cells in a dormant state, with the potential to re-enter the cell cycle along with an increased stemness gene expression. Residual cells after TIS with increased cancer stem cell phenotype may have profound implications for tumor aggressiveness and disease recurrence. Herein, we investigated senescence-associated stemness in EpCAM+/CD133+ liver cancer stem cell and EpCAM-/CD133- nonstem cell populations in HuH7 cell line. We demonstrated that treatment with doxorubicin induces senescence in both cell populations, accompanied by a significant increase in the expression of reprogramming genes SOX2, KLF4, and c-MYC as well as liver stemness-related genes EpCAM, CK19, and ANXA3 and the multidrug resistance-related gene ABCG2. Moreover, doxorubicin treatment significantly increased EpCAM + population in nonstem cells indicating senescence-associated reprogramming of nonstem cell population. Also, Wnt/β-catenin target genes were increased in these cells, while inhibition of this signaling pathway decreased stem cell gene expression. Importantly, Dox-treated EpCAM-/CD133- nonstem cells had increased in vivo tumor-forming ability. In addition, when SASP-CM from Dox-treated cells were applied onto hİPSC-derived hepatocytes, senescence was induced in hepatocytes along with an increased expression of TGF-β, KLF4, and AXIN2. Importantly, SASP-CM was not able to induce senescence in Hep3B-TR cells, a derivative line rendered resistant to TGF-β signaling. Furthermore, ELISA experiments revealed that the SASP-CM of Dox-treated cells contain inflammatory cytokines IL8 and IP10. In summary, our findings further emphasize the importance of carefully dissecting the beneficial and detrimental aspects of prosenescence therapy in HCC and support the potential use of senolytic drugs in HCC treatment in order to eliminate adverse effects of TIS.


Effects of thoracotomy on respiratory system, lung, and chest wall mechanics.
Nineteen rats were sedated, anesthetized, paralyzed, and mechanically ventilated. The respiratory, lung, and chest wall elastances (Est-rs, Est-L, Est-w); respiratory system, pulmonary, and chest wall total resistances (Rtot-rs, Rtot-L, Rtot-w); respiratory system, pulmonary, and chest wall initial resistances (Rinit-rs, Rinit-L, Rinit-w); and respiratory system, pulmonary, and chest wall difference resistances (Rdiff-rs, Rdiff-L, Rdiff-w) were determined before and after thoracotomy using the end-inflation occlusion method. Rinit reflects the Newtonian resistances and Rdiff represents the viscoelastic/inhomogeneous pressure dissipations in the system. Rtot = Rinit+Rdiff, ie, total resistance. The animals were submitted to either anterolateral thoracotomy (group A, n = 7), median sternotomy (group B, n = 6), or median sternotomy under PEEP while the lungs were exposed (group C, n = 6). In groups A and B, statistically significant increases in Rdiff-rs significantly augmented Rtot-rs. The former results were entirely secondary to significant increases in Rdiff-L, which naturally raised Rtot, L. Resistance was not altered in group C rats. Thus, anterolateral thoracotomy and median sternotomy increases Rtot-rs as a consequence of augmented Rdiff-L, but this finding could be prevented by the use of PEEP. Est-rs and Est-L increased in the three groups after surgery. Groups D and E were comprised of four animals each. Both underwent median sternotomy and in group E, PEEP was applied. Histopathologic examination of the lungs demonstrated a higher degree of lung collapse in group D.


Filamentary crystal growth associated with impact craters from hypervelocity microparticles.
A filamentary crystal growth is associated with impacts of hypervelocity microparticles upon copper foil. They are copper whiskers formed by the condensation of the target material vaporzied by the impact.


A role for fibroblast growth factor in oligodendrocyte development.
The differentiation of oligodendrocyte-type 2 astrocyte (O-2A) glial progenitor cells into myelin-forming oligodendrocytes is influenced by several polypeptide growth factors. Exposure of O-2A progenitors to basic fibroblast growth factor (bFGF) promotes their sustained proliferation, blocks their differentiation, and maintains both a high level of platelet-derived growth factor (PDGF) alpha-receptors and PDGF sensitivity. Exposure to PDGF, in contrast, promotes only a limited number of cell divisions prior to their differentiation and triggers progenitor cell migration. In the continued presence of bFGF the cells have a stellate morphology with short processes. Upon addition of PDGF these stellate cells become bipolar with long processes, and on removal of PDGF their morphology reverts back to stellate. Thus the phenotype of O-2A progenitor cells in response to these growth factors is plastic. Our studies suggest that bFGF (or a related ligand) in the CNS may sensitize O-2A progenitors to PDGF and thereby initiate their ability to migrate into white matter tracts prior to the onset of myelination.


Antidepressant therapies inhibit inflammation and microglial M1-polarization.
Macrophages and their counterparts in the central nervous system, the microglia, detect and subsequently clear microbial pathogens and injured tissue. These phagocytic cells alter and adapt their phenotype depending on their prime activity, i.e., whether they participate in acute defence against pathogenic organisms ('M1'-phenotype) or in clearing damaged tissues and performing repair activities ('M2'-phenotype). Stimulation of pattern recognition receptors by viruses (vaccines), bacterial membrane components (e.g., LPS), alcohol, or long-chain saturated fatty acids promotes M1-polarization. Vaccine or LPS administration to healthy human subjects can result in sickness symptoms and low mood. Alcohol abuse and abdominal obesity are recognized as risk factors for depression. In the M1-polarized form, microglia and macrophages generate reactive oxygen and nitrogen radicals to eradicate microbial pathogens. Inadvertently, also tetrahydrobiopterin (BH4) may become oxidized. This is an irreversible reaction that generates neopterin, a recognized biomarker for depression. BH4 is a critical cofactor for the synthesis of dopamine, noradrenaline, and serotonin, and its loss could explain some of the symptoms of depression. Based on these aspects, the suppression of M1-polarization would limit the inadvertent catabolism of BH4. In the current review, we evaluate the evidence that antidepressant treatments (monoamine reuptake inhibitors, PDE4 inhibitors, lithium, valproate, agomelatine, tianeptine, electroconvulsive shock, and vagus nerve stimulation) inhibit LPS-induced microglia/macrophage M1-polarization. Consequently, we propose that supplementation with BH4 could limit the reduction in central monoamine synthesis and might represent an effective treatment for depressed mood.


Combining nilotinib and PD-L1 blockade reverses CD4+ T-cell dysfunction and prevents relapse in acute B-cell leukemia.
Patients with acute lymphoblastic leukemia have experienced significantly improved outcomes due to the advent of chimeric antigen receptor (CAR) T cells and bispecific T-cell engagers, although a proportion of patients still relapse despite these advances. T-cell exhaustion has been recently suggested to be an important driver of relapse in these patients. Indeed, phenotypic exhaustion of CD4+ T cells is predictive of relapse and poor overall survival in B-cell acute lymphoblastic leukemia (B-ALL). Thus, therapies that counter T-cell exhaustion, such as immune checkpoint blockade, may improve leukemia immunosurveillance and prevent relapse. Here, we used a murine model of Ph+ B-ALL as well as human bone marrow biopsy samples to assess the fundamental nature of CD4+ T-cell exhaustion and the preclinical therapeutic potential for combining anti-PD-L1 based checkpoint blockade with tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein. Single-cell RNA-sequence analysis revealed that B-ALL induces a unique subset of CD4+ T cells with both cytotoxic and helper functions. Combination treatment with the tyrosine kinase inhibitor nilotinib and anti-PD-L1 dramatically improves long-term survival of leukemic mice. Depletion of CD4+ T cells prior to therapy completely abrogates the survival benefit, implicating CD4+ T cells as key drivers of the protective anti-leukemia immune response. Indeed, treatment with anti-PD-L1 leads to clonal expansion of leukemia-specific CD4+ T cells with the aforementioned helper/cytotoxic phenotype as well as reduced expression of exhaustion markers. These findings support efforts to use PD1/PD-L1 checkpoint blockade in clinical trials and highlight the importance of CD4+ T-cell dysfunction in limiting the endogenous anti-leukemia response.


Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B.
Streptococcal exotoxins have been implicated in the pathogenesis of a toxic shock-like syndrome and scarlet fever. Previous studies have demonstrated that these toxins are potent stimulators of human T cells and have structural homology to staphylococcal enterotoxins. In the current study, we investigated the mechanism by which streptococcal erythrogenic toxins type A (SPEA) and B (SPEB) activate T cells and compared it with anti-CD3 and the known "superantigen" staphylococcal enterotoxin B. SPEA was found to selectively activate T cells bearing V beta 8, V beta 12, and V beta 14, whereas SPEB selectively activated T cells bearing V beta 2 and V beta 8. Furthermore, fibroblasts transfected with MHC class II molecules were capable of presenting SPEA and SPEB to purified T cells. The T cell response to these toxins, however, was not MHC-restricted. Although the streptococcal exotoxins stimulated both CD4+ and CD8+ T cells, SPEA but not SPEB stimulated the CD4+ T cell subset proportionately more than the CD8+ T cell subset. Our results indicate that SPEA and SPEB, like the staphylococcal enterotoxins, are superantigens and suggest a mechanism by which they may mediate particular systemic syndromes associated with streptococcal infections.


A new synthetic approach to (+)-lactacystin based on radical cyclisation of enantiopure alpha-ethynyl substituted serine derivatives to 4-methylenepyrrolidinones.
Treatment of the acetylenic bromoamide 42c, derived from the enantiopure alpha-amino alcohol 40, with Bu(3)SnH-AlBN results in an efficient 5-exo dig radical cyclisation to the 4-methylenepyrrolidinone 43/44 (2:1). Cleavage of the alkene bond in 43/44, using O(3)-Me(2)S, next gave the corresponding 4-ketopyrrolidinone 45/46. Alpha-phenylsulfanylation of 45/46, using S-methyl-p-toluenethiosulfonate-Et(3)N, proceeded in a stereoselective manner and led to the methylsulfanyl derivative 48 (ca. 9:1 selectivity). Manipulation of the functionality in 48, using two separate sequences, then led to the substituted pyrrolidinones 49b, 50 and 53 which are advanced intermediates in a previous synthesis of (+)-lactacystin 1. In related studies, the acetylenic bromoamide 28a containing all the carbon atoms in lactacystin was synthesised, but this substrate failed to undergo an anticipated radical cyclisation to the 4-methylenepyrrolidinone 30, analogous to 43/44. Instead, only the product of reduction of 28a, i.e. 28b, was produced, possibly resulting from adventitious intramolecular hydrogen-abstraction processes from the carbon centred radical intermediate 29, i.e. 32 to 33 and/or 31 to 34.


A few shared up-regulated genes may influence conidia to yeast transformation in dimorphic fungal pathogens.
The small number of fungi that commonly cause disease in normal people share the capacity to grow as mycelia in the soil at 25°C and as yeast (or spherules) in mammals at 37°C. This remarkable conversion has long been a topic of interest in medical mycology. The conidia to yeast conversion has been studied by transcription profiling in several fungal species, including Histoplasma capsulatum, Paracoccidioides brasiliensis, Coccidioides spp., Blastomyces dermatitidis, and Talaromyces marneffei One limitation of transcriptional profiling is determining which genes are involved in the process of conversion to yeast as opposed to a result of conversion to yeast. If there are genes that are up-regulated in the yeast phase of more than one dimorphic, pathogenic fungus they might be required for conversion to yeast (or spherules). To address this issue, 24 up-regulated genes common to Coccidioides spp spherules and H. capsulatum yeasts were identified. Four homologs of these genes were also found in P. brasiliensis, B. dermatitidis or T. marneffei genes that were up-regulated in yeast. 4-hydroxyphenylpurvate dioxygenase, a gene involved in tyrosine metabolism and melanin synthesis that has been shown to be required for yeast conversion, is conserved and up-regulated in yeast in all five species. Another up-regulated gene that is conserved in all five species is a MFS sugar porter. These results suggest that a minority of up-regulated yeast (or spherule) genes are conserved across species and raises the possibility that conserved up-regulated genes may be of special interest for differentiation of mycelium into yeast.


Novel hyperbranched dendron for gene transfer in vitro and in vivo.
Novel hyperbranched dendron (HD) polymers were synthesized using a low molecular weight poly(ethyleneimine) core (BPEI). Using successive attachment of ethyleneimine moieties to the PEI core, the relative ratio of linear-to-branched structures was lowered from 1.17 to 0.70. We found that the more extensive branching of PEI enables the condensation of plasmid DNA into nanostructures with a size of 70-100 nm. The obtained complexes were stable at least for 3 weeks at 4 degrees C. The HD-DNA complexes prepared using secondary and tertiary amine-containing dendrons exerted a very low cytotoxicity in vitro during a coincubation with cells for 48 h. Using firefly luciferase as a marker of protein expression, we established that HD complexes were efficient in transfecting cells in the presence of serum. Under optimized conditions, the transfection activity at a nitrogen-to-phosphate (N/P) ratio of 6 was approximately six times higher than that of the commercially available polycationic transfection reagent. Bioluminescent imaging of in vivo gene expression using a luciferase reporter gene showed the increase of the signal in the liver and in submandibular lymph nodes in live mice. Our preliminary in vivo gene expression data demonstrates the potential of HD polymers as in vivo transfection agents that could be potentially useful for lymph node gene delivery.


Internal state conversion in ultracold gases.
We consider an ultracold gas of (noncondensed) bosons or fermions with two internal states, and we study the effect of a gradient of the transition frequency between these states. When a pi/2 rf pulse is applied to the sample, exchange effects during collisions transfer the atoms into internal states which depend on the direction of their velocity. This results, after a short time, in a spatial separation between the two states. A kinetic equation is solved analytically and numerically; the results agree well with the recent observations of Lewandowski et al.


60Co-γ radiation induces differential acetylation and phosphorylation of histones H3 and H4 in wheat.
Histone modifications occur during DNA damage and repair in eukaryotes. These modifications were analysed in wheat seedlings exposed to (60) Co-γ radiation. Seedling height was not significantly affected in the first 2 days after irradiation up to 150 Gy. Subsequently, in the next 2 weeks, there was 30-40% reduction in seedling height, indicating that there were late effects of irradiation. The histones isolated from irradiated seedlings were analysed in the initial stages for modifications of H3 and H4 using antibodies. Global acetylation of H3 decreased and H4 increased in a dose-dependent manner till 100 Gy. The time course of individual modifications showed that for H3K4 and H3K9, acetylation decreased, whereas for H3S10 phosphorylation increased. There were fluctuations in acetylation of H4K5, H4K12 and H4K16, whereas H4K8 showed hyper-acetylation. The results indicate that γ radiation induced DNA damage and repair in wheat seedlings and initiated differential acetylation of H3 and H4. This is the first report in plants on site-specific H3 and H4 modifications in response to exposure to ionizing radiation.


The role perception questionnaire (RPQ): a tool for assessing undergraduate students' perceptions of the role of other professions.
A systematic review of interprofessional education (Freeth et al., 2002) revealed that there were many weaknesses in the current body of knowledge of interprofessional education outcomes. One reason for this was the lack of good quality study designs for evaluating the outcomes of interprofessional education. This paper discusses the range of tools that were found in the literature and describes the production and validation of two questionnaires that can be used as part of an interprofessional evaluation strategy. Firstly, a Generic Role Perception Questionnaire which can be used for measuring the perception of the role of a range of professions and a Nursing Role Perception Questionnaire used specifically for measuring the perception of the role of a nurse. Repertory grid technique was selected to elicit constructs from a multiprofessional group of final year undergraduate students. This pool was then used to develop the two questionnaires. Factor analysis, internal consistency and test re-test measures are used along with evidence of validity. The questionnaires were found to have acceptable validity and reliability and could be used as part of an IPE evaluation strategy to measure changes in professional role perception in an undergraduate population.


Hydrogen-bond-assisted epoxidation of homoallylic and allylic alcohols with hydrogen peroxide catalyzed by selenium-containing dinuclear peroxotungstate.
The reaction of peroxotungstates (H(2)WO(4) + H(2)O(2)) with H(2)SeO(4) gave the novel selenium-containing dinuclear tungsten species, (TBA)(2)[SeO(4){WO(O(2))(2)}(2)] (I, TBA = [(n-C(4)H(9))(4)N](+)), which was characterized by elemental analysis, IR, Raman, UV-vis, (77)Se NMR, (183)W NMR, and CSI-MS. Various kinds of homoallylic and allylic alcohols were efficiently epoxidized to the corresponding epoxy alcohols in high yields with 1 equiv. H(2)O(2) with respect to the substrates. Compound I showed the highest catalytic activity for H(2)O(2)-based epoxidation of homoallylic and allylic alcohols among selenium and tungsten complexes. The turnover frequency reached up to 150 h(-1) in a 10 mmol-scale epoxidation of cis-3-hexen-1-ol and this value was the highest among those reported for the transition-metal catalyzed epoxidation of homoallylic alcohols with H(2)O(2). The kinetic, mechanistic, computational studies showed that the stabilization of the transition-state by the hydrogen bonding between I and the substrates results in the high reactivity for the I-catalyzed epoxidation of homoallylic and allylic alcohols. The nature of the hetero atoms in the di- and tetranuclear peroxotungstates with XO(4)(n-) ligands (X = As(V), P(V), S(VI), Si(IV), etc.) was crucial in controlling the Lewis acidity of the peroxotungstates, which significantly affects their electrophilic oxygen transfer reactivity. All the data of the structural, kinetic, spectroscopic, and computational comparison show that the dimeric peroxotungstate unit, {WO(O(2))(2)}(2), in I is activated by the SeO(4)(2-) ligand.


Unique monocistronic operon (ptsH) in Mycoplasma capricolum encoding the phosphocarrier protein, HPr, of the phosphoenolpyruvate:sugar phosphotransferase system. Cloning, sequencing, and characterization of ptsH.
The region of the genome of Mycoplasma capricolum encompassing the gene (ptsH) encoding HPr, a general energy-coupling protein of the phosphoenolpyruvate:sugar phosphotransferase system, was cloned and sequenced. Examination of the sequence revealed a unique arrangement of the ptsH gene. In all other bacterial species characterized thus far, the ptsH gene is part of a polycistronic operon that includes the gene (ptsI) encoding Enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system; the M. capricolum ptsH gene is part of a monocistronic operon that is situated between two open reading frames unrelated to phosphoenolpyruvate:sugar phosphotransferase system function. The gene immediately upstream of ptsH codes for a helicase, and the open reading frame immediately downstream of ptsH, although not homologous to any previously identified protein, contains a signature sequence characteristic of [C-5] cytosine-specific DNA methylases. The product of the ptsH gene has characteristics similar to the HPr protein produced by Gram-positive organisms: it has a greater sequence similarity to HPrs of Gram-positive bacteria than to those of Gram-negative organisms, it is phosphorylated by a protein kinase derived from Gram-positive organisms, and it complements sugar phosphorylation activity in Gram-positive extracts. The high calculated isoelectric point (pI = 9.18) and the absence of glutamate residues in the C-terminal region distinguish the M. capricolum HPr from all previously described HPrs.


Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.
Hypoglossal (XII) motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of mu-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s). We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity. A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the mu-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717) alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons. The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract mu-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced suppression of XII motoneuron activity and resultant impairment of airway patency.


The Role of Transient Receptor Potential A1 and G Protein-Coupled Receptor 39 in Zinc-Mediated Acute and Chronic Itch in Mice.
Itching is a common symptom of many skin or systemic diseases and has a negative impact on the quality of life. Zinc, one of the most important trace elements in an organism, plays an important role in the regulation of pain. Whether and how zinc regulates itching is largely unclear. Herein, we explored the role of Zn2+ in the regulation of acute and chronic itch in mice. It is found that intradermal injection (i.d.) of Zn2+ dose-dependently induced acute itch and transient receptor potential A1 (TRPA1) participated in Zn2+-induced acute itch in mice. Moreover, the pharmacological analysis showed the involvement of histamine, mast cells, opioid receptors, and capsaicin-sensitive C-fibers in Zn2+-induced acute itch in mice. Systemic administration of Zn2+ chelators, such as N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), pyrithione, and clioquinol were able to attenuate both acute itch and dry skin-induced chronic itch in mice. Quantitative polymerase chain reaction (Q-PCR) analysis showed that the messenger RNA (mRNA) expression levels of zinc transporters (ZIPs and ZnTs) significantly changed in the dorsal root ganglia (DRG) under dry skin-induced chronic itch condition in mice. Activation of extracellular signal-regulated kinase (ERK) pathway was induced in the DRG and skin by the administration of zinc or under dry skin condition, which was inhibited by systemic administration of Zn2+ chelators. Finally, we found that the expression of GPR39 (a zinc-sensing GPCR) was significantly upregulated in the dry skin mice model and involved in the pathogenesis of chronic itch. Together, these results indicated that the TRPA1/GPR39/ERK axis mediated the zinc-induced itch and, thus, targeting zinc signaling may be a promising strategy for anti-itch therapy.


The conformation formed by the domain after alanine-155 induces inversion of aspartic acid-151 in alpha A-crystallin from aged human lenses.
A new cleavage site, which is a post-translational modification, was found between residues His-154 and Ala-155 in alpha A-crystallin from the aged human lens. After trypsin digestion of alpha A-crystallin two peptides that include Asp-151 were obtained and have remarkable differences. That is, the stereo-configuration of the Asp-151 in the normal length peptide was predominately inverted to the D-isomer of beta-aspartyl form (D/L of 5.7). However, the stereoconfiguration of the Asp-151 in the cleavage peptide, that lacks the sequence following Ala-155 to the C-terminus, remained predominately in the L-isomer form as indicated by a D/L value of 0.3. The results suggest that the secondary structure in the region of Ala-155 to the C-terminus may constitute a field that causes the inversion of the Asp-151 to the D-isomer form. Since this kind of cleavage was not found in alpha A-crystallin from young lens, the cleavage between His-154 and Ala-155 is probably the result of aging.


Chryseobacterium indologenes Ventilator-Associated Pneumonia in an Elderly Patient: A Case Report.
Chryseobacterium indologenes is a rare non-fermenting gram-negative pathogen that can cause opportunistic infections in humans. Most infections are nosocomial and acquired through contaminated devices such as ventilators, endotracheal tubes, and indwelling catheters. An increasing number of infections have been reported in recent years after the first reported case of ventilator-associated pneumonia in 1993. Blood, lung, ocular, and peritoneal infections, among others, have been reported. The high rate of intrinsic resistance to broad-spectrum antibiotics is a matter of concern since there are no standard guidelines for the management and treatment of this infection. Here, we present the case of a 94-year-old female who was admitted and intubated after a cerebral vascular accident. During her stay, she developed a fever. The deep tracheal aspirate culture was positive for gram-negative bacilli with smooth, circular, and yellow-pigmented colonies that were later identified as C. indologenes. Antimicrobial susceptibility tests done with VITEK 2 and by the Kirby-Bauer disc diffusion method showed susceptibility to ciprofloxacin, minocycline, and trimethoprim-sulfamethoxazole and resistance to all other tested antimicrobials. The infection was successfully treated with ciprofloxacin antibiotic. To the best of our knowledge, this is the first reported case of C. indologenes infection in Lebanon.


Isolation, Solitude and Social Distancing for People Who Use Drugs: An Ethnographic Perspective.
COVID-19 has resulted in deepened states of crisis and vulnerability for people who use drugs throughout Europe and across the world, with social distancing measures having far-reaching implications for everyday life. Prolonged periods of isolation and solitude are acknowledged within much addiction literature as negatively impacting the experiences of those in recovery, while also causing harm to active users - many of whom depend on social contact for the purchasing and taking of substances, as well as myriad forms of support. Solitude, however, is proposed by the authors as inherent within some aspects of substance use, far from particular to the current pandemic. Certain forms of substance use engender solitary experience, even where use is predicated upon the presence of others. Adopting a cross-disciplinary perspective, this paper takes as its focus the urgent changes wrought by the pandemic upon everyday life for people who use drugs, drawing on recent ethnographic fieldwork with substance users in Scotland. Beyond the current crises, the paper proposes solitude, and by extension isolation, as an analytical framework for better apprehending lived experiences of substance use.


Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease.
Exendin-4 is a naturally occurring more potent and stable analog of glucagon-like peptide-1 (GLP-1) that selectively binds at the GLP-1 receptor. It has been recently demonstrated that GLP-1 receptor stimulation preserves dopaminergic neurons in cellular and rodent models of Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of PD neurodegeneration. However, the role of microglia in the neuroprotective properties of exendin-4 is still unknown. Here, we show that, in the mouse MPTP PD model, systemic administration of exendin-4 significantly attenuates the loss of substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic fibers. Exendin-4 prevents MPTP-induced microglial activation in the SNpc and striatum, and the expression of matrix metalloproteinase-3. In addition, exendin-4 also suppressed MPTP-induced expression of pro-inflammatory molecules and tumor necrosis factor alpha and interleukin-1 beta. Our data indicate that exendin-4 may act as a survival factor for dopaminergic neurons by functioning as a microglia-deactivating factor and suggest that exendin-4 may be a valuable therapeutic agent for neurodegenerative diseases such as PD.


A comparison of leg length and femoral offset discrepancies in hip resurfacing, large head metal-on- metal and conventional total hip replacement: a case series.
A discrepancy in leg length and femoral offset restoration is the leading cause of patient dissatisfaction in hip replacement surgery and has profound implications on patient quality of life. The aim of this study is to compare biomechanical hip reconstruction in hip resurfacing, large-diameter femoral head hip arthroplasty and conventional total hip replacement. Sixty patient's post-operative radiographs were reviewed; 20 patients had a hip resurfacing (HR), 20 patients had a Large Head Metal-on-metal (LHM) hip replacement and 20 patients had a conventional small head Total Hip Replacement (THR). The leg length and femoral offset of the operated and unoperated hips were measured and compared. Hip resurfacing accurately restored hip biomechanics with no statistical difference in leg length (P = 0.07) or femoral offset (P = 0.95) between the operated and non-operative hips. Overall HR was superior for reducing femoral offset discrepancies where it had the smallest bilateral difference (-0.2%, P = 0.9). The traditional total hip replacement was least effective at restoring the hip anatomy. The use of a larger-diameter femoral head in hip resurfacing does not fully account for the superior biomechanical restoration, as LHM did not restore femoral offset as accurately. We conclude that restoration of normal hip biomechanics is best achieved with hip resurfacing.


[Spontaneous rectus sheath hematoma: a rare condition with uneasy diagnosis and multidisciplinary treatment. Report of 5 cases and review of literature].
Spontaneous rectus sheath hematoma is a rare condition. It encompasses a wide spectrum of severity (self-limiting to fatal) depending of its size, etiology, and the development of complications. It enters into the differential diagnosis of abdominal pain but it's frequently difficult to diagnose and often radiologic imaging is required. Authors report a series of five patients admitted at emergency room within a 2-year period. Patient were between 63 to 78 years old. One of them was in therapy with warfarin, one was in therapy with acetilsalicililate and clopidogrel and in an another patient a coagulation disorder was detected. Diagnosis was suspected in all cases by clinical exam and ultrasonography, but CT-scan was necessary in three cases. All patients underwent conservative treatment, mainly pain relief and rest. In two cases blood transfusion was performed and in two cases clotting abnormalities were corrected with vitamin K and fresh frozen plasma. Average ospedalization was 10 days (range 5-17). One patient developed late seroma and was treated with ultrasound-guided aspiration. Rectus sheath hematoma is a rare but important entity in the differential diagnosis of abdominal pain. The difficulties in the correct diagnosis frequently lead to delay in treatment or unneeded surgery. CT-scan is the gold-standard investigation. Treatment options are variable and include conservative treatment, intravascular embolization and surgery Frequently an interdisciplinary team approach is needed.


Comparison of techniques for stent assisted coil embolization of aneurysms.
Stent assisted coiling (SAC) of aneurysms has been adopted with potential mechanical, hemodynamic and biologic properties imparting an advantage over coil embolization alone. The purpose of this investigation is to compare the various techniques of SAC at a single institution with regards to clinical, technical and angiographic complications and success. Patients who underwent SAC between 2003 and 2010 were identified. Clinical charts, procedures, angiographic and non-invasive radiological images were analyzed to determine the anatomical and procedural details and adverse events. Immediate post-procedural angiograms as well as follow-up imaging were studied to assess the degree of aneurysm occlusion. 260 aneurysms were identified. The 'coil through' technique was employed in 37.3%, 'balloon stent' in 36.2%, 'jailing' in 10.8% and the 'coil stent' technique in 7.7%. Overall rate of adverse events was higher with the 'coil stent' and 'jailing' techniques compared with the 'balloon stent' technique. The 'coil through' technique was associated with a significantly lower packing density (31.4±20%) than all other techniques ('coil stent' 45.4±22%, 'jailing' 42.2±20%, 'balloon stent' 44.3±22%). Among 'coil stent' patients, an initial Raymond class 1 was achieved in 40%, compared with 57% of 'jailing', 28% of 'coil through' and 63% of 'balloon stent' cases. Balloon assisted coil embolization followed by adjunctive stent deployment across the aneurysm neck appears to be the superior technique among stent assisted coiling methods at our institution. It combines a lower rate of thrombotic and coil related complications with a high rate of complete occlusion on initial and follow-up imaging.


Effect of genetically modified poplars on soil microbial communities during the phytoremediation of waste mine tailings.
The application of transgenic plants to clean up environmental pollution caused by the wastes of heavy metal mining is a promising method for removing metal pollutants from soils. However, the effect of using genetically modified organisms for phytoremediation is a poorly researched topic in terms of microbial community structures, despite the important role of microorganisms in the health of soil. In this study, a comparative analysis of the bacterial and archaeal communities found in the rhizosphere of genetically modified (GM) versus wild-type (WT) poplar was conducted on trees at different growth stages (i.e., the rhizospheres of 1.5-, 2.5-, and 3-year-old poplars) that were cultivated on contaminated soils together with nonplanted control soil. Based on the results of DNA pyrosequencing, poplar type and growth stages were associated with directional changes in the structure of the microbial community. The rate of change was faster in GM poplars than in WT poplars, but the microbial communities were identical in the 3-year-old poplars. This phenomenon may arise because of a higher rate and greater extent of metal accumulation in GM poplars than in naturally occurring plants, which resulted in greater changes in soil environments and hence the microbial habitat.


Expression of extracellular matrix proteoglycans perlecan and decorin in carbon-tetrachloride-injured rat liver and in isolated liver cells.
Proteoglycans are important components of the extracellular matrix. They are involved in liver regeneration as well as in liver fibrosis. The distribution and cellular source of proteoglycans under normal as well as pathological conditions is still under debate. Localization of decorin and perlecan was studied in normal, acutely damaged, and cirrhotic liver by histochemistry. Furthermore, their synthesis was analyzed in different liver cell populations isolated from normal rat liver. In normal liver, decorin positivity was observed in the perisinusoidal space and in the portal area. Perlecan was clearly detectable in the portal area (blood vessels and bile ducts); a moderate reaction was also seen along the sinusoids. Strong positivity for both proteoglycans was detectable in the necrotic areas of acutely damaged liver. Chronic liver damage was characterized by the deposition of decorin and perlecan in the fibrotic septa. Immunocytochemical reactions were positive for perlecan and decorin in cultured Ito and endothelial cells but not in hepatocytes and Kupffer cells. Northern hybridization confirmed the capacity of Ito cells and endothelial cells to express the two genes. Interestingly, although rat skin fibroblasts expressed strong messages for both proteoglycans, rat aortic smooth muscle cells did not synthesize decorin.


BDE-47 induces oxidative stress, activates MAPK signaling pathway, and elevates de novo lipogenesis in the copepod Paracyclopina nana.
Brominated flame retardant, 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47), has received grave concerns as a persistent organic pollutant, which is toxic to marine organisms, and a suspected link to endocrine abnormalities. Despite the wide distribution in the marine ecosystem, very little is known about the toxic impairments on marine organisms, particularly on invertebrates. Thus, we examined the adverse effects of BDE-47 on life history trait (development), oxidative markers, fatty acid composition, and lipid accumulation in response to BDE-47-induced stress in the marine copepod Paracyclopina nana. Also, activation level of mitogen-activated protein kinase (MAPK) signaling pathways along with the gene expression profile of de novo lipogenesis (DNL) pathways were addressed. As a result, BDE-47 induced oxidative stress (e.g. reactive oxygen species, ROS) mediated activation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK) signaling cascades in MAPK pathways. Activated MAPK pathways, in turn, induced signal molecules that bind to the transcription factors (TFs) responsible for lipogenesis to EcR, SREBP, ChREBP promoters. Also, the stress stimulated the conversion of saturated fatty acids (SFAs) to polyunsaturated fatty acids (PUFAs), a preparedness of the organism to adapt the observed stress, which could be correlated with the elongase and desaturase gene (e.g. ELO3, Δ5-DES, Δ9-DES) expressions, and then extended to the delayed early post-embryonic development and increased accumulation of lipid droplets in P. nana. This study will provide a better understanding of how BDE-47 effects on marine invertebrates particularly on the copepods, an important link in the marine food chain.


Developing a New Dimension for Fourier Domain Optical Coherence Tomography Images by Simultaneous Measurement of the Refractive Index and Thickness.
Introduction: Fourier domain Optical coherence tomography (OCT) is a widely used high-resolution optical imaging technique. It is useful for various applications in medical imaging, such as ophthalmology (e.g. retinal imaging for diagnosing complications like glaucoma or macular degeneration), dermatology, oncology, and cardiology. The ability to noninvasively measure both the refractive index and thickness of biological tissues could have various medical applications and enable earlier disease detection. For example, observing changes in the refractive index can help distinguish between tissues with normal or abnormal function. Methods: In this study, the theoretical framework for simultaneous measurement of the refractive index and physical thickness of multilayer systems is proposed and tested for two different samples, each having three layers, a glass/NaCl solution/glass sample and a glass/sugar solution/glass sample. The whole signal processing procedure and the experimental setup are described. Results: The refractive index and thickness of salt water and sugar water samples in the Fourier-domain OCT (FD-OCT) system were obtained. The resulting data were compared with reference measurements and showed a deviation of about 1% for the samples. Conclusion: We tested the proposed framework for the simultaneous extraction of the refractive index and thickness of multilayer systems of salt water and sugar water from its FD-OCT data. We showed that the measured parameters were in agreement with reference amounts.


Structure, Activity and Function of the PRMT2 Protein Arginine Methyltransferase.
PRMT2 belongs to the protein arginine methyltransferase (PRMT) family, which catalyzes the arginine methylation of target proteins. As a type I enzyme, PRMT2 produces asymmetric dimethyl arginine and has been shown to have weak methyltransferase activity on histone substrates in vitro, suggesting that its authentic substrates have not yet been found. PRMT2 contains the canonical PRMT methylation core and a unique Src homology 3 domain. Studies have demonstrated its clear implication in many different cellular processes. PRMT2 acts as a coactivator of several nuclear hormone receptors and is known to interact with a multitude of splicing-related proteins. Furthermore, PRMT2 is aberrantly expressed in several cancer types, including breast cancer and glioblastoma. These reports highlight the crucial role played by PRMT2 and the need for a better characterization of its activity and cellular functions.


Decreased nitric oxide synthesis in human endothelial cells cultured on type I collagen.
Endothelial dysfunction, considered as a defective vascular dilatation after certain stimuli, is characteristic of different pathological conditions, such as hypertension, atherosclerosis, or diabetes. A decreased synthesis or an increased degradation of nitric oxide (NO) has been postulated as the mechanism responsible for this alteration. The present experiments were designed to test the hypothesis that the presence of an abnormal extracellular matrix in vessel walls could be responsible for the decreased NO synthesis observed in these pathological conditions. Experiments were performed in cultured human umbilical vein endothelial cells (HUVECs) grown on type IV (Col. IV) or type I (Col. I) collagen. Cells seeded on Col. I showed decreased nitrite synthesis, nitric oxide synthase activity, eNOS protein content, and eNOS mRNA expression when compared with cells grown on Col. IV. Moreover, cells grown on Col. I failed to respond to glucose oxidase activation of the eNOS system. In both cases, the changes in the eNOS mRNA expression seemed to depend on the modulation of eNOS promoter activity. The downregulation of eNOS induced by Col. I was blocked by D6Y, a peptide that interferes with the Col. I-dependent signals through integrins, as well as by specific anti-integrin antibodies. Moreover, a decreased activation of integrin-linked kinase (ILK) may explain the effects observed in Col. I-cultured cells because the activity of this kinase was decreased in these cells and ILK modulation prevented the Col. I-induced changes in HUVECs. Taken together, these findings may contribute to explaining the basis of endothelial dysfunction in some vascular diseases.


Immune cell functional assay in monitoring of adult liver transplantation recipients with infection.
To identify the levels of functional immunity measured by the ImmuKnow assay in Chinese liver transplantation recipients and its application in monitoring the risk of posttransplant infection. Forty-five apparent healthy Chinese and 106 adult liver transplant (LT) recipients were under investigation. LTs were grouped in stable status or infection according to their clinical diagnosis. Whole blood samples were collected freshly and cultured within 6 hr, the CD4(+) T cells were selected, and their adenosine triphosphate (ATP) value was assayed the next day. Before stimulation, we also examined the percentage of T-helper (Th; CD3(+) CD4(+)) and T-suppress (Ts; CD3(+) CD8(+)) lymphocyte subpopulations and the ratio of Th/Ts. The average ImmuKnow assay in infectious LT recipients was 128 + or - 84 ng/mL, significantly lower (P<0.05) than that in stable LTs (305 + or - 149 ng/mL) or in normal adults (301+ or - 101 ng/mL). The ImmuKnow values in LTs had a good negative correlation to infection clinically (r = -0.6217, P<0.001). Infectious risk was high when the ImmuKnow value was less than 130 ng/mL (odds ratio=13, 95% confidence interval 6.0-29.4, P<0.01). The sensitivity of low ImmuKnow values in posttransplant infection was 85.2%, significantly higher than those of Th/Ts ratio and immunosuppressant trough levels (P<0.01); specificity was 76.3%, comparable with that of Th/Ts ratio (75.5%), but greatly higher than immunosuppressant trough levels (P<0.01). ImmuKnow ATP values had no correlation with Th/Ts ratio or immunosuppressant trough levels. ImmuKnow ATP levels are lower in LT recipients with infection, which provides a new tool in monitoring posttransplant infection, and an index of tailoring immunosuppression clinically.


Distraction test of the posterior superior iliac spine (PSIS) in the diagnosis of sacroiliac joint arthropathy.
The sacroiliac joint (SIJ) is a frequently underestimated cause of lower back (LBP). A simple clinical test of sufficient validity would be desirable. The aim of this study was to evaluate the diagnostic value of a new PSIS distraction test for the clinical detection of SIJ arthropathy and to compare it to several commonly used clinical tests. Consecutive patients, where a SIJ pathology had been confirmed by an SIJ infiltration were enrolled (case group, 61 SIJs in 46 patients). Before infiltration, patients were tested for pain with PSIS distraction by a punctual force on the PSIS in medial-to-lateral direction (PSIS distraction test), pain with pelvic compression, pelvic distraction, Gaenslen test, Thigh Thrust, and Faber (or Patrick's) test. In addition, these clinical tests were applied to both SIJs of a population of individuals without history of LBP (control group, 64 SIJs in 32 patients). Within the investigated cohort, the PSIS distraction test showed a sensitivity of 100% and a specificity of 89% for SIJ pathology. The accuracy of the test was 94%, the positive predictive value (PPV) was 90% and the negative predictive value (NPV) was 100%. Pelvic compression, pelvic distraction, Gaenslen test, Thigh Thrust, and Faber test were associated with a good specificity (> 90%) but a poor sensitivity (< 35%). Within our population of patients with confirmed SIJ arthropathy the PSIS distraction test was found to be of high sensitivity, specificity and accuracy. In contrast, common clinical tests showed a poor sensitivity. The PSIS distraction test seems to be an easy-to-perform and clinically valuable test for SIJ arthropathy.


Median cleft of the lower lip: report of two new cases and review of the literature.
Median clefts of the lower lip and mandible are rare craniofacial clefts. Couronné in 1819 was the first to describe the condition. The midline cleft of the lower lip was classified by Tessier as a type 30 craniofacial cleft. Recently, the total number of the reported cases had increased to about 66 in the world literature. In addition, 2 more patients are presented here. The first case involves only a small notch in the vermilion; the deformity was treated by Z-plasty. In the second case, a midline incomplete cleft of the lower lip, a sublingual abnormal frenulum, a complete cleft in the mandible, a bifid sternum, a presternal skin tag, and a ventricular septal defect in the heart were present. At operation, Z-plasty of the lingual frenulum released the normal-sized tongue. The lip cleft was corrected by a simple V excision followed by closure in 3 layers. The mandibular segments were "vitalized" with a bone rongeur and immobilized in the predetermined position with an interosseous stainless steel wire. Because the bone fusion was complete, the stainless steel wire was taken out after 3 months so that it would not prevent mandibular development. Our treatment methods and others are discussed.


Recurrent Respiratory Papillomatosis (RRP)-Juvenile Onset.
In this article, we describe the treatment of long standing juvenile-onset recurrent respiratory papillomatosis (JORRP) with eventual transformation to carcinoma in a patient who lived to the age of 73. Treatment modalities consisted of bronchoscopy and local excision initially. Later, YAG and CO2 laser debulking were used. Radiotherapy, chemotherapy with carboplatin (300 mg/m2) and 5-FU (600 mg/m2), oral methotrexate (5-7.5 mg/week), pegylated Interferon, indole-3-carbamide, and intralesional cidofovir were also utilized in the treatment of this patient. Except for methotrexate, each of the treatment regimens used in this patient, initially decreased growth of the papillomas and improved symptoms experienced by the patient. Interestingly, we found that this patient's long standing JORRP initially responded to a chemotherapy regimen of 4 cycles of carboplatin (300 mg/m2) and 5-FU (600 mg/m2) as well. Ultimately, the disease became resistant to all forms of treatment and progressed. The patient eventually succumbed to the disease after an approximate 77 year course.


Innovations in coaching and mentoring: implications for nurse leadership development.
This longitudinal study sought to examine ways in which coaching and mentoring relationships impact on the professional development of nurses in terms of career and leadership behaviours, and evaluating the differences and similarities between those coaching and mentoring relationships. According to the UK government, leadership in nursing is essential to the improvement of service delivery, and the development and training of all nurses is vital in achieving effective change. A coaching and mentoring programme was used to explore the comparative advantages of these two approaches for the leadership development of nurses in acute, primary care and mental health settings. A longitudinal in-depth study was conducted to measure differences and similarities between the mentoring and coaching process as a result of a six-month coaching/mentoring programme. Five nurses from six UK Health Care Trusts were allocated to a coaching group (n = 15) or a mentoring group (n = 15), these were coached or mentored by a member of the senior directorate from their own Trust. Qualitative and quantitative data were collected at three time points (T1 = baseline, T2 = 4 months and T3 = 9 months) using semi-structured interviews and questionnaires. While mentoring was perceived to be 'support' and coaching was described as 'action', descriptions of the actual process and content were quite similar. However, while both groups reported significant development in terms of career development, leadership skills and capabilities, mentees reported the highest level of development with significantly higher scores in eight areas of leadership and management and in three areas of career impact. Implications for nurses and health services are discussed.


The Munich Wistar Frömter rat: proteinuria and blood pressure in correlation to the number of superficial glomeruli.
Rats with a high number of superficial nephrons (MWF/Ztm) also show an elevated urinary protein excretion and a high systolic blood pressure. To investigate a possible correlation between the number of superficial glomeruli and these physiological changes, MWF/Ztm rats were crossed and backcrossed to Wistar cryptorchic (WC/Ztm) animals with no superficial nephrons in order to produce genotypes with differing numbers of superficial glomeruli. In the parental strains, the F1 hybrids and the 8 possible backcrosses, the number of superficial glomeruli, the distance of the 10 most superficial glomeruli to the renal surface, and the diameter of Bowman's capsules were determined by morphometric analysis. The excretion of total protein, in detail low molecular weight proteins, albumin, and high molecular weight proteins were measured quantitatively in 5 males of each genotype. Systolic blood pressure was determined by a tail-cuff method in conscious rats. Means of each variate of the 12 available genotypes were linearly correlated and demonstrate a close correlation between the amount of superficial nephrons and the observed physiological changes, i.e. the more superficial the glomeruli the higher the urinary protein excretion, especially albumin, and the higher the systolic blood pressure.


Spatial fluctuations affect the dynamics of motor proteins.
Motor proteins are active biological molecules that perform their functions by converting chemical energy into mechanical work. They move unidirectionally along rigid protein filaments or DNA and RNA molecules in discrete steps by hydrolyzing ATP (adenosine triphsophate) or related energy-rich compounds. Recent single-molecule experiments have shown that motor proteins experience significant spatial fluctuations during its motion, leading to broad step-size distributions. The effect of these spatial fluctuations is analyzed explicitly by considering discrete-state stochastic models that allow us to compute exactly all dynamic properties. It is shown that for symmetric spatial fluctuations there is no change in mean velocities for weak external forces, while dispersions and stall forces are strongly affected at all conditions. These results are illustrated by several simple examples. Our method is also applied to analyze the effect of step-size fluctuations on dynamics of myosin V motor proteins. It is argued that spatial fluctuations might be used to control and regulate the dynamics of motor proteins.


Modified one-day etoposide and cisplatin combination for previously untreated extensive-disease small-cell lung cancer: A retrospective evaluation of 36 cases.
The combination of etoposide and cisplatin (EP) remains one of the standard first-line treatments for extensive-disease small-cell lung cancer (ED-SCLC) We devised a one-day modified EP regimen for better tolerance and convenience by modifying the dose and schedule of conventional EP with administration over 3-5 consecutive days. The modified EP consists of two infusions of etoposide (120 mg/m2 each) and 60 mg/m2 of cisplatin on day 1 of a 21-day cycle and a maximum of 6 cycles of treatment. A total of 36 consecutive ED-SCLC patients were treated with the modified EP as first-line therapy and retrospectively reviewed to assess the efficacy and safety of this regimen. Of the 36 patients, 24 exhibited confirmed objective tumor response (overall response rate of 66%, with a complete response rate of 3% and a partial response rate of 63%). The median overall survival (OS) was 11.8 months [95% confidence interval (CI): 7.9-15.3] and the progression-free survival (PFS) was 7.3 months (95% CI: 5.2-9.7). The survival estimates at 1 year were 35 and 17% for OS and PFS, respectively. The chemotherapy treatment was well tolerated, with only one case of grade 4 non-hematological adverse events, no grade 4 hematological toxicities and no treatment-related deaths. The mean relative dose intensity of etoposide and cisplatin was measured to be 94.7 and 98.5% of the planned dose, respectively. Therefore, the modified EP warrants further clinical research regarding its effectiveness, toxicity profile and convenience of administration. Prospective randomized clinical trials are required to determine the therapeutic role of the modified EP as first-line treatment in patients with ED-SCLC.


Prophylactic use of a standardized botanical extract for the prevention of naturally occurring diarrhea in newborn Holstein calves.
The objectives of this study were to evaluate the prophylactic use of SB-300 (Jaguar Animal Health, San Francisco, CA), a standardized botanical extract isolated from the bark latex of Croton lechleri, on reducing fecal water losses and diarrhea events in Holstein bull calves individually housed under a restricted whole-milk feeding regimen (6 L/d) from 1 to 25 d of life. Fluid therapy administration due to dehydration, average weight gain, and the fecal microbiome were also evaluated. Bull calves used in this study were born from normal parturition, fed 4 L of pooled pasteurized colostrum by esophageal feeder, and moved to a research facility at Cornell University (Ithaca, NY). A double-blinded randomized clinical trial was designed to allocate a total of 40 newborn calves into 1 of 2 treatment groups: calves receiving (twice daily) a solution containing 500 mg of SB-300 added to the whole milk for the first 15 d of life (SB-300, n = 20) or a control group receiving sterile water added to whole milk for the same period (CTR, n = 20). Treatment solutions had a total volume of 10 mL per treatment. Data regarding fecal dry matter were collected to precisely measure water content in fecal samples and to define diarrhea events; the SB-300 group had significantly increased fecal dry matter during the study period. Additionally, significantly fewer events of diarrhea were observed for calves in the SB-300 group (16.9%) compared with calves in the CTR group (46.5%). Dehydration status was evaluated and treated accordingly; calves with moderate dehydration were offered oral electrolytes, and calves with severe dehydration were rescued with intravenous fluid therapy. Calves in the SB-300 group had fewer intravenous fluid therapies administered during the study period (1.6%) compared with the CTR group (3.1%). Overall fluid therapy administered (oral electrolytes plus intravenous fluids) was significantly higher for the CTR group (9.2%) compared with the SB-300 group (6.1%) during the study period. No differences in milk consumption, calf starter intake, or weight gain were observed between treatment groups. A single time increase in Bifidobacterium was observed on d 20 of life for the SB-300 group; otherwise, no differences in fecal microbiome profile were detected between treatment groups. These results suggest that 500 mg of SB-300 added to the milk for 15 d can reduce the incidence of diarrhea and reduce severe dehydration in milk-fed calves.


ERADICATION OF BRUCELLA MELITENSIS FROM TWO CAPTIVE GAZELLE POPULATIONS IN SAUDI ARABIA.
An outbreak of brucellosis occurred in a group of 726 sand gazelles (Gazella marica) at the Prince Mohammed Al-Sudairi Gazelle Breeding Center and in a group of 47 putative "Neumann's gazelles" (Gazella erlangeri) housed at the King Khalid Wildlife Research Center in Saudi Arabia. Clinical signs of anorexia, poor body condition, enlarged testes, reluctance to walk, swollen carpal joints, and suppurative arthritis were present in 16 sand gazelles and 14 Neumann's gazelles. All clinical cases were evaluated using a card agglutination test, complement fixation, and enzyme-linked immunosorbent assay. All cases were serologically positive for Brucella melitensis, confirmed through culture and isolation of the microorganism. DNA was extracted from the isolated organisms, and polymerase chain reaction (PCR) was used for sequencing. Evaluation focused on tracking the source of infection, the management of the two outbreaks, and the subsequent diagnosis, treatments, and success, including the successful eradication of Brucella from both populations.


Deep-Learning-Based Automated Neuron Reconstruction From 3D Microscopy Images Using Synthetic Training Images.
Digital reconstruction of neuronal structures from 3D microscopy images is critical for the quantitative investigation of brain circuits and functions. It is a challenging task that would greatly benefit from automatic neuron reconstruction methods. In this paper, we propose a novel method called SPE-DNR that combines spherical-patches extraction (SPE) and deep-learning for neuron reconstruction (DNR). Based on 2D Convolutional Neural Networks (CNNs) and the intensity distribution features extracted by SPE, it determines the tracing directions and classifies voxels into foreground or background. This way, starting from a set of seed points, it automatically traces the neurite centerlines and determines when to stop tracing. To avoid errors caused by imperfect manual reconstructions, we develop an image synthesizing scheme to generate synthetic training images with exact reconstructions. This scheme simulates 3D microscopy imaging conditions as well as structural defects, such as gaps and abrupt radii changes, to improve the visual realism of the synthetic images. To demonstrate the applicability and generalizability of SPE-DNR, we test it on 67 real 3D neuron microscopy images from three datasets. The experimental results show that the proposed SPE-DNR method is robust and competitive compared with other state-of-the-art neuron reconstruction methods.


Wound Healing Studies Using Punica granatum Peel: An Animal Experimental Study.
The goal of the present study was to evaluate the effects of hydroalcoholic extract-based carboxy methyl cellulose (CMC) gel of Punica granatum peel (PCMC) and CMC on healing of full-thickness skin wounds. Forty-two rats were studied. Each rat had 3 wounds that were treated topically with PCMC as the case, CMC as the positive control, and sterile saline as the negative control. All 3 wounds of each rat were photographed during the wound healing period at days 0 (onset of wound surgery), 3, 6, 9, and 12.The wound area was calculated using Adobe Photoshop CS (version 5) software (Adobe Systems Inc, San Jose, California). Electrocardiogram paper was used for reference scale. The results of this study show that macroscopic and microscopic wound healing took a significantly longer time in wounds treated with normal saline than those treated with PCMC (grossly) and CMC gel (grossly and significantly). The authors' findings show that anti-inflammatory, antihemorrhagic, and antinecrotic effects of CMC lead to early healing of skin wounds.


Prevalence and most common causes of disability among adults--United States, 2005.
Since 1994, disability-related costs for medical care and lost productivity have exceeded an estimated $300 billion annually in the United States. To update previous reports on the prevalence and most common causes of disability among adults, CDC and the U.S. Census Bureau analyzed the most recent data from the Survey of Income and Program Participation (SIPP). This report summarizes the findings of that analysis, which indicated that the prevalence of disability in 2005 (21.8%) remained unchanged from 1999 (22.0%); however, because of the aging of the population, particularly the large group born during 1946-1964 ("baby boomers"), the estimated absolute number of persons reporting a disability increased 7.7%, from 44.1 to 47.5 million. The three most common causes of disability continued to be arthritis or rheumatism (affecting an estimated 8.6 million persons), back or spine problems (7.6 million), and heart trouble (3.0 million). Women (24.4%) had a significantly higher prevalence of disability compared with men (19.1%) at all ages. For both sexes, the prevalence of disability doubled in successive age groups (18-44 years, 11.0%; 45-64 years, 23.9%; and >/=65 years, 51.8%). The number of adults reporting a disability likely will increase, along with the need for appropriate medical and public health services, as more persons enter the highest risk age group (>/=65 years). To accommodate the expected increase in demand for disability-related medical and public health services, expanding the reach of effective strategies and interventions aimed at preventing progression to disability and improving disability management in the population is necessary.


A case of Bonneau syndrome associated with multiple renal cortical cysts.
We describe a 2-month-old girl with congenital anomalies including facial anomalies, complex cardiac anomalies, polysyndactyly, dysgenesis of distal extremities and bilateral multiple renal cysts. The proband was the child of first-cousin parents. Clinical synopsis in Bonneau syndrome (OMIM: 263630) is polysyndactyly and cardiac malformation. In addition, liver anomalies were reported in two patients. We discuss polysyndactyly and cardiac malformation with bilateral multiple renal cysts, a combination not reported previously.


Understanding Ligand-Exchange Reactions on Thiolate-Protected Gold Clusters by Probing Isomer Distributions Using Reversed-Phase High-Performance Liquid Chromatography.
Thiolate-protected gold clusters (Aun(SR)m) have attracted considerable attention as functional nanomaterials in a wide range of fields. A ligand-exchange reaction has long been used to functionalize these clusters. In this study, we separated products from a ligand-exchange reaction of phenylethanethiolate-protected Au24Pd clusters (Au24Pd(SC2H4Ph)18), in which Au25(SR)18 is doped with palladium, into each coordination isomer with high resolution by reversed-phase high-performance liquid chromatography. This success has enabled isomer distributions of the products to be quantitatively evaluated. We evaluated quantitatively the isomer distributions of products obtained by the reaction of Au24Pd(SC2H4Ph)18 with thiol, disulfide, or diselenide. The results revealed that the exchange reaction starts to occur preferentially at thiolates that are bound directly to the metal core (thiolates of a core site) in all reactions. Further study on the isomer-separated Au24Pd(SC2H4Ph)17(SC12H25) revealed that clusters vary the coordination isomer distribution in solution by the ligand-exchange reaction between clusters and that control of the coordination isomer distribution of the starting clusters enables control of the coordination isomer distribution of the products generated by ligand-exchange reactions between clusters. Au24Pd(SC2H4Ph)18 used in this study has a similar framework structure to Au25(SR)18, which is one of the most studied compounds in the Aun(SR)m clusters. Knowledge gained in this study is expected to enable further understanding of ligand-exchange reactions on Au25(SR)18 and other Aun(SR)m clusters.


Mental well-being among patients with congenital heart disease and heart failure during the COVID-19 pandemic.
Patients with congenital heart disease (CHD) show increasing survival. We evaluated the influence of COVID-19 confinement on the mental well-being of patients with CHD. Descriptive, cross-sectional, observational epidemiological study in a cohort of 242 patients with CHD over 14 years old recruited consecutively from a single adolescent and adult CHD outpatient unit. Patients were sent an online questionnaire to determine clinical, demographic and the 12-element general health questionnaire (GHQ-12) data during the COVID-19 quarantine. 242 out of 407 (59%) patients with CHD, to whom the questionnaire was sent, responded to the survey. 98 (42%) patients were between 14 and 24 years old and 133 (58%) were over 25 years old. Of the total, 119 (51%) were male. 123 (51%), 88 (36%) and 31 (13%) patients with CHD had mild, moderate, and severe anatomical complexity respectively. 11 (4.5%) out of 242 patients with CC presented heart failure (HF) symptoms, requiring 18% of them admission to the hospital emergency department during the pandemic (P=0.002). In relation to the GHQ-12 questionnaire, patients with CHD and HF enjoyed less their daily activities (81% vs. 51%, P=0.043) and had less self-confidence (46% vs. 18%, P=0.041) than those without HF symptoms. In conclusion, patients with CHD and HF, during the COVID-19 quarantine, presented a lower capacity to enjoy daily activities and self-confidence than CHD without HF symptoms.


Application and Evaluation of Novel Chromatographic Techniques to Detect and Quantitate 108 Pesticides and Metabolites in Muscle Samples From Wild Birds of Prey.
The application and evaluation of highly efficient chromatographic techniques with tandem mass spectrometry for the detection and quantitation of 108 pesticides and metabolites, some considered persistent organic pollutants, was performed in muscle samples obtained from 25 birds of prey belonging to the families Accipitridae, Falconidae, and Strigidae presented dead in 2013 to Grupo de Rehabilitación de la Fauna Autóctona y su Hábitat, in Madrid, Spain. Pesticides with prohibited use were detected at high concentrations in the muscle samples analyzed. Based on its high sensitivity to detect pesticides in muscle, the described chromatographic techniques with tandem mass spectrometry should be considered an alternative testing methodology to those commonly used for routine application in ecotoxicological forensic research.


Physical nature of ethidium and proflavine interactions with nucleic acid bases in the intercalation plane.
On the basis of the crystallographic structures of three nucleic acid intercalation complexes involving ethidium and proflavine, we have analyzed the interaction energies between intercalator chromophores and their four nearest bases, using a hybrid variation-perturbation method at the second-order Møller-Plesset theory level (MP2) with a 6-31G(d,p) basis set. A total MP2 interaction energy minimum precisely reproduces the crystallographic position of the ethidium chromophore in the intercalation plane between UA/AU bases. The electrostatic component constitutes the same fraction of the total energy for all three studied structures. The multipole electrostatic interaction energy, calculated from cumulative atomic multipole moments (CAMMs), was found to converge only after including components above the fifth order. CAMM interaction surfaces, calculated on grids in the intercalation planes of these structures, reasonably reproduce the alignment of intercalators in crystal structures; they exhibit additional minima in the direction of the DNA grooves, however, which also need to be examined at higher theory levels if no crystallographic data are given.