Biosynthesis of silver nanoparticles by a new strain of Streptomyces sp. compared with Aspergillus fumigatus.
Locally isolated strains of a thermoalkalotolerant Streptomyces sp. and Aspergillus fumigatus were used for the in vitro biosynthesis of silver nanoparticles from AgNO(3) solutions. An autolysed cell-free culture filtrate from each strain was used, indicating that the formation mechanism depends on intra-cellular components for both organisms, since culture broths had no significant nanoparticle formation potential. Nanoparticle formation was indicated by a change of the solution from colourless or light brown to dark brown after 24 h or more, and UV-visible spectroscopy and x-ray diffraction analysis confirmed the formation by both organisms. The initial formation kinetics were faster with Aspergillus, but formation continued for a longer period with Streptomyces, resulting in higher concentrations after 48 h. Transmission electron microscope images revealed well dispersed nanoparticles with diameters ranging from 15 to 45 nm from A. fumigatus, while those from Streptomyces sp. had a narrower size distribution of 15-25 nm. The higher productivity and preferred narrower size distribution of Streptomyces, together with its well established industrial use, may make it the preferred choice for further optimization studies.


Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response.
Proliferation of vascular smooth muscle cells (VSMCs) in response to injury plays a key role in the pathogenesis of vascular disorders. Fas ligand (FasL) induces apoptosis in Fas-bearing cells, and its expression on activated T cells contributes to the regulation of the immune response and physiological cell turnover. Here, we show that a replication-defective adenovirus encoding FasL (Ad-FasL) induced apoptosis in Fas-bearing VSMCs. When introduced locally to balloon-injured rat carotid arteries, a well characterized model of a VSMC-derived lesion, Ad-FasL functioned as a potent inhibitor of neointima formation. In rats immunized with an empty adenoviral vector, robust T cell infiltration of the vessel wall was detected after local delivery of a beta-galactosidase-expressing virus (Ad-betagal), whereas T cell infiltrates were not detected after local delivery of Ad-FasL. Prior immunization prevented beta-galactosidase expression from Ad-betagal, whereas the expression of the FasL transgene was unaffected. When Ad-betagal and Ad-FasL were delivered together to preimmunized animals, T cell infiltration was reduced and beta-galactosidase expression was restored. These data demonstrate that Fas ligand gene transfer can effectively inhibit injury-induced vessel lesion formation and can allow adenovirus-harboring cells to evade immune destruction.


[Interaction of SV40 T-antigen with homologous and heterologous DNA].
Using the DNA filter binding assay, the effects of ionic strength and pH on SV40 T-antigen interaction with viral DNA were studied. The apparent association constants for T-antigen binding to SV40 DNA in Scatchard coordinates in the presence of 40 mM NaCl are equal to 0.67 . 10(6) M-1 (pH 6.0) and 0.86 x 10(7) M-1 (pH 7.4). These data indicate that the interaction between T-antigen and SV40 DNA is more specific at pH 7.4. The coincident values of association constants for T-antigen binding to viral and cellular DNAs (Ka = 0.9 x 10(7) M-1 for cellular DNA) at pH 7.4 and the absence of competition between the two DNA species upon binding with T-antigen suggest that viral and cellular DNAs possess similar sites for T-antigen binding. Denatured DNA competes with viral DNA only at pH 6.0, when the T-antigen--SV40 DNA interaction is less specific.


K-ras p21 expression and activity in lung and lung tumors.
Although K-ras is mutated in many human and mouse lung adenocarcinomas, the function of K-ras p21 in lung is not known. We sought evidence for the prevalent hypothesis that K-ras p21 activates raf, which in turn passes the signal through the extracellular signal regulated kinases (Erks) to stimulate cell division, and that this pathway is upregulated when K-ras is mutated. Results from both mouse lung tumors and immortalized cultured E10 and C10 lung type II cells failed to substantiate this hypothesis. Lung tumors did not have more total K-ras p21 or K-ras p21 GTP than normal lung tissue, nor were high levels of these proteins found in tumors with mutant K-ras. Activated K-ras p21-GTP levels did not correlate with proliferating cell nuclear antigen. Special features of tumors with mutant K-ras included small size of carcinomas compared with carcinomas lacking this mutation, and correlation of proliferating cell nuclear antigen with raf-1. In nontransformed type II cells in culture, both total and activated K-ras p21 increased markedly at confluence but not after serum stimulation, whereas both Erk1/2 and the protein kinase Akt were rapidly activated by the serum treatment. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays of K-ras mRNA indicated an increase in confluent and especially in postconfluent cells. Together the findings indicate that normal K-ras p21 activity is associated with growth arrest of lung type II cells, and that the exact contribution of mutated K-ras p21 to tumor development remains to be discovered.


Implementation and Impact of an Antimicrobial Stewardship Program at a Tertiary Care Center in South India.
Antimicrobial resistance is a major public health threat internationally but, particularly in India. A primary contributing factor to this rise in resistance includes unregulated access to antimicrobials. Implementing antimicrobial stewardship programs (ASPs) in the acute hospital setting will help curb inappropriate antibiotic use in India. Currently, ASPs are rare in India but are gaining momentum. This study describes ASP implementation in a large, academic, private, tertiary care center in India. An ASP was established in February 2016 consisting of an administrative champion, hospitalist, microbiologist, intensivist, and pharmacists. Antimicrobial stewardship program interventions included postprescriptive audit and establishment of institutional guidelines. The ASP tracked appropriate drug selection including loading dose, maintenance dose, frequency, route, duration of therapy, de-escalation, and compliance with ASP recommendations. Defined daily dose (DDD) of drugs and cost of antimicrobials were compared between the pre-implementation phase (February 2015-January 2016) and post-implementation phase (February 2016-January 2017). Of 48 555 patients admitted during the post-implementation phase, 1020 received 1326 prescriptions for restricted antibiotics. Antibiotic therapy was appropriate in 56% (742) of the total patient prescriptions. A total of 2776 instances of "inappropriate" antimicrobial prescriptions were intervened upon by the ASP. Duration (806, 29%) was the most common reason for inappropriate therapy. Compliance with ASP recommendations was 54% (318). For all major restricted drugs, the DDD/1000 patient days declined, and there was a significant reduction in mean monthly cost by 14.4% in the post-implementation phase. Implementation of a multidisciplinary antibiotic stewardship program in this academic, large, Indian hospital demonstrated feasibility and economic benefits.


Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fast- and slow-twitch skeletal muscles of calorie-restricted rats.
Calorie restriction [CR; ~65% of ad libitum (AL) intake] improves insulin-stimulated glucose uptake (GU) and Akt phosphorylation in skeletal muscle. We aimed to elucidate the effects of CR on 1) processes that regulate Akt phosphorylation [insulin receptor (IR) tyrosine phosphorylation, IR substrate 1-phosphatidylinositol 3-kinase (IRS-PI3K) activity, and Akt binding to regulatory proteins (heat shock protein 90, Appl1, protein phosphatase 2A)]; 2) Akt substrate of 160-kDa (AS160) phosphorylation on key phosphorylation sites; and 3) atypical PKC (aPKC) activity. Isolated epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles from AL or CR (6 mo duration) 9-mo-old male F344BN rats were incubated with 0, 1.2, or 30 nM insulin and 2-deoxy-[(3)H]glucose. Some CR effects were independent of insulin dose or muscle type: CR caused activation of Akt (Thr(308) and Ser(473)) and GU in both muscles at both insulin doses without CR effects on IRS1-PI3K, Akt-PP2A, or Akt-Appl1. Several muscle- and insulin dose-specific CR effects were revealed. Akt-HSP90 binding was increased in the epitrochlearis; AS160 phosphorylation (Ser(588) and Thr(642)) was greater for CR epitrochlearis at 1.2 nM insulin; and IR phosphorylation and aPKC activity were greater for CR in both muscles with 30 nM insulin. On the basis of these data, our working hypothesis for improved insulin-stimulated GU with CR is as follows: 1) elevated Akt phosphorylation is fundamental, regardless of muscle or insulin dose; 2) altered Akt binding to regulatory proteins (HSP90 and unidentified Akt partners) is involved in the effects of CR on Akt phosphorylation; 3) Akt effects on GU depend on muscle- and insulin dose-specific elevation in phosphorylation of Akt substrates, including, but not limited to, AS160; and 4) greater IR phosphorylation and aPKC activity may contribute at higher insulin doses.


Community structure of rare methanogenic archaea: insight from a single functional group.
The rare biosphere, the low abundant microbial populations, is suggested to be a conserved way of microbial life. Here we conducted a molecular survey of rare methanogenic archaea in the environment targeting the mcrA gene in order to test if general concepts associated with the structure of the rare bacterial biosphere also apply to single functional groups. Similar to what is known about rare bacterial communities, the contribution of rare methanogens to the alpha diversity is much larger than to Bray-Curtis measures. Moreover, a similar core group of methanogens harbored by the abundant and rare communities suggests similar sources and environmental controls of both groups. Among the communities of different levels of rarity, the conditionally rare methanogenic taxa largely account for the overall community dynamics of the rare biosphere and likely enter the dominant community under favorable environmental conditions. In addition, we observed a positive correlation between the alpha diversity and the production of methane when the rare taxa were taken into account. This supports the concept that increasing microbial biodiversity enhances ecological function. The composition and environmental associations of the rare methanogenic biosphere allow us to conclude that rarity is a conserved way also for single functional groups.


Diagnosis of SARS-CoV-2: A Review on the Current Scenario and Future Outlook.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undoubtedly created an emerging disease of topmost public health priority spilling throughout the globe. The diagnosis currently relies on a multiplex of criteria including the epidemiology, clinical manifestations and in vitro diagnostics. Presently, the real-time reverse transcriptase-PCR (rRT-PCR) is considered as the most reliable assay for the detection of SARS-CoV-2 and is being supplemented by other auxiliary tests, including serology and radiology. Many of these molecular and immunological tests have been validated by the Indian Council of Medical Research (ICMR) and the Food and Drug Administration (FDA) and commercial kits have been introduced in the field. But, considering the sensitivity and specificity based shortcomings and the lacunae in monitoring the spread of the virus, there is an immense need to develop integrated smart devices based on novel, safe, rapid and accurate diagnostic techniques and implement them on a large scale to curb this outbreak in the country and the world as a whole. Keywords: clinical manifestations; COVID-19; diagnosis; PCR; SARS-COV-2; serology.


The creation and implementation of an outpatient pulmonary embolism treatment protocol.
The ability to rapidly and accurately risk-stratify patients with venous thromboembolism (VTE), and the availability of direct acting oral anticoagulants have reduced the need for intravenous anticoagulation for patients with deep vein thrombosis (DVT) and pulmonary embolism (PE). Emergency physicians are generally reluctant to discharge patients with VTE without defined and reliable follow up in place, and VTE patients treated with anticoagulants can be at risk for complications related to recurrent VTE and bleeding. In addition, screening for associated diseases (e.g. cancer, hypercoagulable states) may be indicated. Therefore, the outpatient treatment of low risk VTE requires coordinated effort and reliable follow up. By leveraging detailed outcome data and collaborative relationships, we have created a protocol for the safe outpatient treatment of patients with low risk DVT and PE. Our protocol is data driven and designed to address barriers to outpatient VTE management. We expect our protocol to result in improved patient satisfaction, more efficient emergency department (ED) throughput, and decreased cost. Applied nationally, the outpatient treatment of select patients with DVT and PE could have major public health and economic impact.


The role of a labial salivary gland biopsy in the diagnostic procedure for Sjögren's syndrome; a study of 94 cases.
The purpose of the present study is to examine the role of the outcome of the labial salivary gland biopsy (LSGB) in the diagnostic procedure of patients suspected of suffering from Sjögren's syndrome (SS). In a retrospective study the result of histopathological assessment of 94 consecutively taken labial salivary gland biopsies has been examined. For the diagnosis of SS the American-European Consensus Group classification (AECG, 2002) have been used. The outcome of the assessment has been discussed in relation to a recently reported classification provided by the American College of Rheumatology (ACR, 2012). In the 94 LSGBs support for a diagnosis of SS has been encountered in 24 out of 26 patients with SS. In the 68 patients with a negative diagnosis of SS only six positive LSGBs were observed. The sensitivity of the labial biopsy amounted 0.92; the specificity was 0.91, while the positive predictive value and the negative predictive value amounted 0.80 and 0.97 respectively. LSGBs taken by or on the request of the departments of Rheumatology or Internal Medicine had a significant higher yield compared to LSGBs taken in other clinical departments. The LSGB may play a role in the diagnostic procedure of Sjögren's syndrome when using either the AECG classification or the ACR classification. A LSGB should preferably taken after counseling for the possible presence of SS by a department of Rheumatology or Internal Medicine since the yield of such biopsies is much higher than in patients who have not been counseled by these departments prior to the taking of a LSGB. When using the ACR classification, a positive serologic result and a positive ocular test make the taking of a LSGB redundant. Only in case of a negative serologic outcome or a negative result of the ocular test a LSGB is indicated. Since both the serologic test and the ocular test carry hardly any morbidity, these tests should, indeed, be performed first before considering to take a LSGB.


Neuroleptic malignant syndrome in children and adolescents.
Neuroleptic malignant syndrome is a rare but potentially fatal complication of treatment with antipsychotic medications. Prior to 1994, there was no accepted set of diagnostic criteria. This article presents four adolescents admitted at Cleveland Clinic Foundation from 1985 to 1998, illustrating the broad spectrum of neuroleptic malignant syndrome. A review of the pediatric literature is discussed as to the current risk factors, pathogenesis, management, and outcome. Early recognition and supportive and specific treatment of neuroleptic malignant syndrome reduced the morbidity and mortality.


The development of various generations of nephrons during postnatal ontogenesis in the rat.
The structural development of individual nephrons has been investigated in the kidneys of young rats by microdissection. Superficial, intercortical and juxtamedullary nephrons in Wistar-Konarovice rats aged 2 to 60 days have been followed. At two and five days of age the superficial nephrons were in an early stage of anatomical development. At this time intercortical and juxtamedullary nephrons were more developed, and basically resembled similar structures in adult animals with the exception that the loops of Henle did not have a thin ascending limb. At ten days of age all three types of nephrons were differentiated with the exception that the intercortical nephrons did not possess a thin ascending limb of Henle's loop. At selected stages of development there appears to be a direct relation between the length of the superficial nephrons and the weight of the kidney. Since individual segments of these nephrons do not grow at the same proportional rate, this relationship does not hold when compared to kidney weight.


[Using a new generation of classification system of antineoplastic drugs to guide Chinese medicine research].
A new generation of classification system of antineoplastic drugs was put forward based on comparing the first with the second generation classification system of antineoplastic drugs. Antineoplastic drugs are divided into cytotoxic drug, cells biological behavior regulator, biological response modifier and biochemical modulator. The using of biological response modifier (immune modulator for instance) and biochemical modulator are supplementary methods for Western medicine treatment in tumor, because the cytotoxic effects of Chinese herbs are lower than those of chemotherapeutic drugs. For the new breakthrough of Chinese medicine oncology research, new idea, new technology and new target should be used, the Chinese medicine mechanism should be studied from a new view. Reversing abnormal biological behavior of tumor cells by Chinese medicine could be an important breakthrough of Chinese medicine oncology research.


Experiences of primary caregivers of children with cerebral palsy across the trajectory of diagnoses in Ghana.
Cerebral palsy (CP) is a non-progressive disorder of posture or movement caused by a lesion to the developing brain that results in functional limitations. The diagnosis of CP can vary from one child to another, causing family stress because of vague and unknown outcomes of the disorder. Although there are negative attitudes in Ghanaian societies towards primary caregivers and children with disabilities, fewer attempts have been made to understand their experiences. The main aim of this study was to explore the experiences of primary caregivers across the trajectory of the diagnosis (before, during and after) of CP in the setting of a tertiary hospital. Using Social Capital Theory as framework, 40 primary caregivers of children with CP, who were receiving treatment at a major referral hospital in Ghana, were interviewed about their experiences before, during and after diagnosis. The results that emerged from the thematic analysis were discussed as follows: experiences before diagnosis, experiences during the diagnosis and experiences after the diagnosis. Particularly, participants discussed their inability to access essential services such as education for their children with CP. In light of systemic challenges faced by participants and their children with CP, the need for health policymakers to prioritise the public education about CP, promoting the well-being of caregivers and other implications of the study have been discussed.


Genetic structure and demographic history of Colletotrichum gloeosporioides sensu lato and C. truncatum isolates from Trinidad and Mexico.
C. gloeosporioides sensu lato is one of the most economically important post-harvest diseases affecting papaya production worldwide. There is currently no information concerning the genetic structure or demographic history of this pathogen in any of the affected countries. Knowledge of molecular demographic parameters for different populations will improve our understanding of the biogeographic history as well as the evolutionary and adaptive potential of these pathogens. In this study, sequence data for ACT, GPDH, β-TUB and ITS gene regions were analyzed for C. gloeosporioides sensu lato and C. truncatum isolates infecting papaya in Trinidad and Mexico in order to determine the genetic structure and demographic history of these populations. The data indicated that Mexico is the ancestral C. gloeosporioides sensu lato population with asymmetrical migration to Trinidad. Mexico also had the larger effective population size but, both Mexico and Trinidad populations exhibited population expansion. Mexico also had greater nucleotide diversity and high levels of diversity for each gene. There was significant sub-division of the Trinidad and Mexico populations and low levels of genetic divergence among populations for three of the four gene regions; β-TUB was shown to be under positive selection. There were also dissimilar haplotype characteristics for both populations. Mutation may play a role in shaping the population structure of C. gloeosporioides sensu lato isolates from Trinidad and from Mexico, especially with respect to the ACT and GPDH gene regions. There was no evidence of gene flow between the C. truncatum populations and it is possible that the Mexico and Trinidad populations emerged independently of each other. The study revealed relevant information based on the genetic structure as well as the demographic history of two fungal pathogens infecting papaya, C. gloeosporioides sensu lato and C. truncatum, in Trinidad and Mexico. Understanding the genetic structure of pathogen populations will assist in determining the evolutionary potential of the pathogen and in identifying which evolutionary forces may have the greatest impact on durability of resistance. Intervention strategies that target these evolutionary forces would prove to be the most practical.


The differential expression of PilY1 proteins by the HsfBA phosphorelay allows twitching motility in the absence of exopolysaccharides.
Type Four Pili (T4P) are extracellular appendages mediating several bacterial functions such as motility, biofilm formation and infection. The ability to adhere to substrates is essential for all these functions. In Myxococcus xanthus, during twitching motility, the binding of polar T4P to exopolysaccharides (EPS), induces pilus retraction and the forward cell movement. EPS are produced, secreted and weakly associated to the M. xanthus cell surface or deposited on the substrate. In this study, a genetic screen allowed us to identify two factors involved in EPS-independent T4P-dependent twitching motility: the PilY1.1 protein and the HsfBA phosphorelay. Transcriptomic analyses show that HsfBA differentially regulates the expression of PilY1 proteins and that the down-regulation of pilY1.1 together with the accumulation of its homologue pilY1.3, allows twitching motility in the absence of EPS. The genetic and bioinformatic dissection of the PilY1.1 domains shows that PilY1.1 might be a bi-functional protein with a role in priming T4P extension mediated by its conserved N-terminal domain and roles in EPS-dependent motility mediated by an N-terminal DUF4114 domain activated upon binding to Ca2+. We speculate that the differential transcriptional regulation of PilY1 homologs by HsfBA in response to unknown signals, might allow accessorizing T4P tips with different modules allowing twitching motility in the presence of alternative substrates and environmental conditions.


[Immediate recovery from acute renal insufficiency after abdominal decompression].
A 61-year-old man received an aorto-iliac reconstruction after he was admitted because of a ruptured abdominal aortic aneurysm. Postoperatively, he developed cardiopulmonary insufficiency with anuria. After the intra-abdominal pressure had risen to 40 cmH2O (measured by a urinary bladder catheter), it was decided to perform a relaparotomy. Immediately after abdominal decompression--without correction of any other intra-abdominal pathology--the diuresis increased and several other cardiopulmonary parameters improved significantly. When a critically ill patient shows a rapid increase of the intra-abdominal pressure above a critical level an acute abdominal compartment syndrome may develop. This syndrome consists mainly of potentially fatal cardiopulmonary and renal insufficiency, for which (re)laparotomy with abdominal decompression is the only correct treatment.


Transfer Learning for the Detection and Diagnosis of Types of Pneumonia including Pneumonia Induced by COVID-19 from Chest X-ray Images.
Accurate early diagnosis of COVID-19 viral pneumonia, primarily in asymptomatic people, is essential to reduce the spread of the disease, the burden on healthcare capacity, and the overall death rate. It is essential to design affordable and accessible solutions to distinguish pneumonia caused by COVID-19 from other types of pneumonia. In this work, we propose a reliable approach based on deep transfer learning that requires few computations and converges faster. Experimental results demonstrate that our proposed framework for transfer learning is a potential and effective approach to detect and diagnose types of pneumonia from chest X-ray images with a test accuracy of 94.0%.


Social and structural aspects of the overdose risk environment in St. Petersburg, Russia.
While overdose is a common cause of mortality among opioid injectors worldwide, little information exists on opioid overdoses or how context may influence overdose risk in Russia. This study sought to uncover social and structural aspects contributing to fatal overdose risk in St. Petersburg and assess prevention intervention feasibility. Twenty-one key informant interviews were conducted with drug users, treatment providers, toxicologists, police, and ambulance staff. Thematic coding of interview content was conducted to elucidate elements of the overdose risk environment. Several factors within St. Petersburg's environment were identified as shaping illicit drug users' risk behaviours and contributing to conditions of suboptimal response to overdose in the community. Most drug users live and experience overdoses at home, where family and home environment may mediate or moderate risk behaviours. The overdose risk environment is also worsened by inefficient emergency response infrastructure, insufficient cardiopulmonary or naloxone training resources, and the preponderance of abstinence-based treatment approaches to the exclusion of other treatment modalities. However, attitudes of drug users and law enforcement officials generally support overdose prevention intervention feasibility. Modifiable aspects of the risk environment suggest community-based and structural interventions, including overdose response training for drug users and professionals that encompasses naloxone distribution to the users and equipping more ambulances with naloxone. Local social and structural elements influence risk environments for overdose. Interventions at the community and structural levels to prevent and respond to opioid overdoses are needed for and integral to reducing overdose mortality in St. Petersburg.


Radiation damage during in situ electron microscopy of DNA-mediated nanoparticle assemblies in solution.
Oligonucleotide-nanoparticle conjugates, also called programmable atom equivalents, carry promise as building blocks for self-assembled colloidal crystals, reconfigurable or stimuli responsive functional materials, as well as bio-inspired hierarchical architectures in wet environments. In situ studies of the DNA-mediated self-assembly of nanoparticles have so far been limited to reciprocal space techniques. Liquid-cell electron microscopy could enable imaging such systems with high resolution in their native environment but to realize this potential, radiation damage to the oligonucleotide linkages needs to be understood and conditions for damage-free electron microscopy identified. Here, we analyze in situ observations of DNA-linked two-dimensional nanoparticle arrays, along with control experiments for different oligonucleotide configurations, to identify the mechanisms of radiation damage for ordered superlattices of DNA-nanoparticle conjugates. In a biological context, the results point to new avenues for studying direct and indirect radiation effects for small ensembles of DNA in solution by tracking conjugated nanoparticles. By establishing low-dose conditions suitable for extended in situ imaging of programmable atom equivalents, our work paves the way for real-space observations of DNA-mediated self-assembly processes.


A Program Aimed at Reducing Anxiety in Pregnant Women Diagnosed With a Small-for-Gestational-Age Fetus: Evaluative Findings From a Spanish Study.
The objective of this study was to evaluate the effect of anxiety-reducing techniques including music therapy, sophrology, and creative visualization in pregnant women with a fetus diagnosed as small for gestational age and improved fetal and neonatal weight. This was a quasi-experimental study with a nonrandomized clinical trial design. We compared 2 groups of pregnant women with a fetus diagnosed as small for gestational age with no abnormalities on Doppler studies. The control group (n = 93) received standard care, and the intervention group (n = 65), in addition to standard care, underwent a program of 6 sessions led by a midwife or nurse who taught anxiety-reduction techniques. The State-Trait Anxiety Inventory (STAI) including trait and state subscales were completed by both groups at the start of the study, and only the STAI-State subscale was completed again at the end of the study. Comparisons between the 2 groups regarding fetal weight and centile and maternal STAI scores were performed using the t test and the χ test. There were no significant differences in the STAI-Trait scores between the 2 groups. There were statistically significant differences in the intervention group's STAI-State score percentiles between the start and the end of the study, being lower at the end of the study (P < .001). There were significant differences between the 2 groups in fetal weight trajectory on the basis of fetal weight: the intervention group had a larger weight gain (P < .005). The program designed to reduce anxiety in pregnant women was effective at reducing anxiety in the women in the intervention group, leading to a favorable fetal weight trajectory in this group.


The protective effects of wine pomace products on the vascular endothelial barrier function.
Endothelial dysfunction is associated with cardiovascular diseases and involves a chronic inflammatory process that together with oxidative stress increases the permeability of the vascular endothelium. The aim of this study was to evaluate the role of red and white wine pomace products (rWPPs and wWPPs) in the maintenance of endothelial integrity in hyperglycemia of EA.hy926 endothelial cells. EA.hy926 endothelial cells exposed to hyperglycemia were treated with the in vitro digested fractions of rWPPs and wWPPs. A Real Time Cellular Analysis (RTCA) system was used to evaluate the endothelial monolayer integrity after INF-γ stimulation of pre-treated endothelial cells with the digested fractions. The changes in cell viability, NO, ROS and NOX4 were recorded and actin cytoskeleton and E-cadherin junctions were evaluated by immunofluorescence. All digested fractions prevent the hyperglycemic actions in the cell viability and NO/ROS balance. The inflammatory mediator INF-γ and hyperglycemia caused a decrease in RTCA adhesion of the EA.hy926 endothelial cell monolayer. Pre-treatment with all digested fractions enhanced the EA.hy926 endothelial monolayer integrity and maintained actin cytoskeleton and E-cadherin junctions. These in vitro studies elucidate that the anti-hyperglycemic and anti-inflammatory actions of wine pomace products involve a decrease in ROS production and the stabilization of junction proteins via modulation of VE-cadherin and actin cytoskeleton suggesting a potential prevention of endothelial damage by these natural products.


Interferon-induced revertants of ras-transformed cells: resistance to transformation by specific oncogenes and retransformation by 5-azacytidine.
Prolonged alpha/beta interferon (IFN-alpha/beta) treatment of NIH 3T3 cells transformed by a long terminal repeat-activated Ha-ras proto-oncogene resulted in revertants that maintained a nontransformed phenotype long after IFN treatment had been discontinued. Cloned persistent revertants (PRs) produced large amounts of the ras-encoded p21 and were refractile to transformation by EJras DNA and by transforming retroviruses which carried the v-Ha-ras, v-Ki-ras, v-abl, or v-fes oncogene. Transient treatment either in vitro or in vivo with cytidine analogs that alter gene expression by inhibiting DNA methylation resulted in transformation of PR, but not of NIH 3T3, cells. The PR retransformants reverted again with IFN, suggesting that DNA methylation is involved in IFN-induced persistent reversion.


A case of congenital leukemia cutis.
Congenital leukemia is a rare disease that develops from birth to 6 weeks of life. Leukemia cutis involves cutaneous infiltration by leukemic cells and is an unusual manifestation of leukemia, and has been documented in 25~30% of patients with congenital leukemia. The authors report a case of congenital leukemia cutis. A newborn male presented with widespread firm dusky red papules and nodules on almost his entire body surface. Skin biopsy specimens confirmed the presence of leukemic infiltrations, and bone marrow cytology was consistent with acute myeloid leukemia of the FAB M5 type.


Method for Extraction and Quantification of Metal-Based Nanoparticles in Biological Media: Number-Based Biodistribution and Bioconcentration.
A multistep sample preparation method was developed to separate metal-based engineered nanoparticles (ENPs) from biological samples. The method was developed using spiked zebrafish tissues and standard titanium dioxide (TiO2) and cerium dioxide (CeO2) ENPs. Single-particle inductively coupled plasma mass spectrometry was used to quantify the separated particles in terms of number concentration. This method demonstrated mass recoveries of more than 90% and did not strikingly alter the median particles size. High number recoveries were calculated for CeO2 ENPs (>84%). Particle number recoveries were poor for TiO2 ENPs (<25%), which could be due to the interference of 48Ca with the measured isotope 48Ti. The method was verified using zebrafish exposed to CeO2 ENPs to test its applicability for nanotoxicokinetic investigations. Total mass of Ce and particle number concentration of CeO2 ENPs were measured in different tissues. Notably, the mass-based biodistribution of Ce in the tissues did not follow the number-based biodistribution of CeO2. Moreover, the calculated mass-based bioconcentration factors showed a different pattern in comparison to the number-based bioconcentration factors. Our findings suggest that considering mass as the sole dose-metric may not provide sufficient information to investigate toxicity and toxicokinetics of ENPs.


Diagnosing intrinsic sphincteric deficiency: comparing urethral closure pressure, urethral axis, and Valsalva leak point pressures.
Our purpose was to compare three measures proposed to diagnose intrinsic sphincteric deficiency: maximum urethral closure pressure, Valsalva leak point pressure, and straining urethral axis. A total of 159 women with pure genuine stress incontinence had the three measures determined in a standardized fashion. Critical cutoff values for the Valsalva leak point pressure (52 cm) and urethral axis (22 degrees) were established by examining relative frequency distribution curves, using closure pressure of 20 as the arbitrary benchmark value for the prevalence of intrinsic sphincteric deficiency. The distribution of cutoff values is described and differences among the measures with respect to risk factors for intrinsic sphincteric deficiency and incontinence severity were determined. Half the subjects fell below at least one cutoff value, but only 10% fell below all three. Sixty-four percent of subjects with either low closure pressure or leak point pressure had low values for the other, whereas 21% had discordance between them. Only 53% of subjects with low closure pressure and 40% with low leak point pressure had an axis < or = 22 degrees. Conversely, a substantial portion (36%) of subjects with pure genuine stress incontinence without urethral hypermobility had neither low urethral or leak point pressures. All three cutoff-values were associated with risk factors for intrinsic sphincteric deficiency, but only low closure and leak point pressures had significant associations with the severity of incontinence. Intrinsic sphincteric deficiency should be diagnosed by a composite of historic, urodynamic, anatomic, and clinical severity criteria. We would include a maximum urethral closure pressure < or = 20, a Valsalva leak point pressure < or = 50, and a stress urethral axis < or = 20 in this composite.


PEEP-induced changes in lung volume in acute respiratory distress syndrome. Two methods to estimate alveolar recruitment.
Lung volumes, especially functional residual capacity (FRC), are decreased in acute respiratory distress syndrome (ARDS). Positive end-expiratory pressure (PEEP) contributes to increased end-expiratory lung volume (EELV) and to improved oxygenation, but differentiating recruitment of previously nonaerated lung units from distension of previously open lung units remains difficult. This study evaluated simple methods derived from bedside EELV measurements to assess PEEP-induced lung recruitment while monitoring strain. Prospective multicenter study in 30 mechanically ventilated patients with ARDS in five university hospital ICUs. Two PEEP levels were studied, each for 45 min, and EELV (nitrogen washout/washin technique) was measured at both levels, with the difference (Δ) reflecting PEEP-induced lung volume changes. Alveolar recruitment was measured using pressure-volume (PV) curves. High and low recruiters were separated based on median recruitment at high PEEP. Minimum predicted increase in lung volume computed as the product of ΔPEEP by static compliance was subtracted from ΔEELV as an independent estimate of recruitment. Estimated and measured recruitments were compared. Strain induced by PEEP was also calculated from the same measurements. FRC was 31 ± 11% of predicted. Median [25th-75th percentiles] PEEP-induced recruitment was 272 [187-355] mL. Estimated recruitment correlated with recruited volume measured on PV curves (ρ = 0.68), with a slope close to identity. The ΔEELV/FRC ratio differentiated high from low recruiters (110 [76-135] vs. 55 [23-70]%, p = 0.001). Strain increase due to PEEP was larger in high recruiters (p = 0.002). PEEP-induced recruitment and strain can be assessed at the bedside using EELV measurement. We describe two bedside methods for predicting low or high alveolar recruitment during ARDS.


Who benefits from allogeneic transplantation for myelodysplastic syndromes?: new insights.
Recently, a refined cytogenetic and molecular classification fundamentally changed the prognostication of patients with myelodysplastic syndromes (MDS). The increasingly complex heterogeneity of this disease entity is mirrored by life expectancy rates ranging from almost a decade for very low-risk disease down to several months in higher-risk patients, even with conventional treatments. Intensive treatment approaches are hampered by the older age of most of the patients, potentially leading to an unacceptable adverse event rate. This is especially true for allogeneic hematopoietic stem cell transplantation (HCT), which, albeit of curative intent, can lead to considerable morbidity and mortality mostly as a result of organ toxicity, infectious complications, and GVHD. Furthermore, innovative drug developments, including hypomethylating agents, have broadened the therapeutic armamentarium and, although not curative, can lead to durable responses in subgroups of patients with higher-risk MDS. In fact, there is still no prospective randomized trial available that formally demonstrates the benefit of allogeneic HCT compared with standard treatments in MDS patients. In the absence of randomized data, when considering allogeneic HCT, emphasis should be put on patient selection and optimization of the pre- and posttransplantation treatment period. In these patients, a thorough comorbidity evaluation is mandatory and stratification according to age, cytogenetics, cytopenias, disease-related quality of life, and available alternative treatments should be performed in deciding whether, when, and how to perform allogeneic HCT.


Cu2+ inhibition of gel secretion in the xylem and its potential implications for water uptake of cut Acacia holosericea stems.
Maintaining a high rate of water uptake is crucial for maximum longevity of cut stems. Physiological gel/tylosis formation decreases water transport efficiency in the xylem. The primary mechanism of action for post-harvest Cu(2+) treatments in improving cut flower and foliage longevity has been elusive. The effect of Cu(2+) on wound-induced xylem vessel occlusion was investigated for Acacia holosericea A. Cunn. ex G. Don. Experiments were conducted using a Cu(2+) pulse (5 h, 2.2 mM) and a Cu(2+) vase solution (0.5 mM) vs a deionized water (DIW) control. Development of xylem blockage in the stem-end region 10 mm proximal to the wounded stem surface was examined over 21 days by light and transmission electron microscopy. Xylem vessels of stems stood into DIW were occluded with gels secreted into vessel lumens via pits from surrounding axial parenchyma cells. Gel secretion was initiated within 1-2 days post-wounding and gels were detected in the xylem from day 3. In contrast, Cu(2+) treatments disrupted the surrounding parenchyma cells, thereby inhibiting gel secretion and maintaining the vessel lumens devoid of occlusions. The Cu(2+) treatments significantly improved water uptake by the cut stems as compared to the control.


Bacillus anthracis comparative genome analysis in support of the Amerithrax investigation.
Before the anthrax letter attacks of 2001, the developing field of microbial forensics relied on microbial genotyping schemes based on a small portion of a genome sequence. Amerithrax, the investigation into the anthrax letter attacks, applied high-resolution whole-genome sequencing and comparative genomics to identify key genetic features of the letters' Bacillus anthracis Ames strain. During systematic microbiological analysis of the spore material from the letters, we identified a number of morphological variants based on phenotypic characteristics and the ability to sporulate. The genomes of these morphological variants were sequenced and compared with that of the B. anthracis Ames ancestor, the progenitor of all B. anthracis Ames strains. Through comparative genomics, we identified four distinct loci with verifiable genetic mutations. Three of the four mutations could be directly linked to sporulation pathways in B. anthracis and more specifically to the regulation of the phosphorylation state of Spo0F, a key regulatory protein in the initiation of the sporulation cascade, thus linking phenotype to genotype. None of these variant genotypes were identified in single-colony environmental B. anthracis Ames isolates associated with the investigation. These genotypes were identified only in B. anthracis morphotypes isolated from the letters, indicating that the variants were not prevalent in the environment, not even the environments associated with the investigation. This study demonstrates the forensic value of systematic microbiological analysis combined with whole-genome sequencing and comparative genomics.


The role of negative affects as mediators in the relationship between stress and mental health in Ecuadorian adolescents.
Stress and negative emotions have adverse consequences for the mental health of adolescents, an area that deserves further examination. These attributes are associated with each other and regularly interact in different ways. The way they exert an influence can be both direct and indirect, so the general objective is to elucidate the potential mediating effect of negative affects in the relationship between stress and mental health in Ecuadorian adolescents. An explanatory and mediation design based on structural equation modeling (SEM) was applied with 1154 high school students from Ecuador (67.7% women) aged 14 to 19 years (M = 15.69). In our sample, the presence of stress and negative affect is moderate, while that of mental health problems is low. According to our final model, these variables covary with and influence each other in the following way: stress (X) has a direct effect on mental health (Y) and also an indirect effect mediated by negative affect (M). The structural regression model proposed explains 63.0% of the variance in mental health. Stress exerts a relevant impact on mental health, both through direct and indirect pathways. The indirect pathway, mediated by negative affect, opens the door to novel interventional strategies to foster mental health.


Na-Pi cotransport in LLC-PK1 cells: fast adaptive response to Pi deprivation.
A short-term regulation of the Na-dependent transport of Pi in LLC-PK1 cells by the extracellular concentration of Pi is described. Pi deprivation of the cells for 10 min led to an increase (30%) of the Na-Pi cotransport activity, whereas the Na-dependent D-glucose transport system was not affected. This regulatory phenomenon was not affected by the presence of cycloheximide. The same adaptive response was observed in apical membrane vesicles isolated from rapidly adapted cells. In the isolated membranes, increased Na-Pi cotransport is characterized by an increase of the maximal rate of uptake (control: 193 +/- 15; adapted: 306 +/- 51 pmol X mg-1 X 15 s-1), whereas the apparent Km for Pi remained constant. The results suggest that LLC-PK1 cells possess a mechanism or mechanisms that allow a rapid "activation" and "inactivation" of Na-dependent Pi transport systems as a function of the concentration of the extracellular Pi.


Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models.
Liver metastasis is a clinically significant contributor to the mortality associated with melanoma, colon, and breast cancer. Preclinical mouse models are essential to the study of liver metastasis, yet their utility has been limited by the inability to study this dynamic process in a noninvasive and longitudinal manner. This study shows that three-dimensional high-frequency ultrasound can be used to noninvasively track the growth of liver metastases and evaluate potential chemotherapeutics in experimental liver metastasis models. Liver metastases produced by mesenteric vein injection of B16F1 (murine melanoma), PAP2 (murine H-ras-transformed fibroblast), HT-29 (human colon carcinoma), and MDA-MB-435/HAL (human breast carcinoma) cells were identified and tracked longitudinally. Tumor size and location were verified by histologic evaluation. Tumor volumes were calculated from the three-dimensional volumetric data, with individual liver metastases showing exponential growth. The importance of volumetric imaging to reduce uncertainty in tumor volume measurement was shown by comparing three-dimensional segmented volumes with volumes estimated from diameter measurements and the assumption of an ellipsoid shape. The utility of high-frequency ultrasound imaging in the evaluation of therapeutic interventions was established with a doxorubicin treatment trial. These results show that three-dimensional high-frequency ultrasound imaging may be particularly well suited for the quantitative assessment of metastatic progression and the evaluation of chemotherapeutics in preclinical liver metastasis models.


IoT Based Smart Monitoring of Patients' with Acute Heart Failure.
The prediction of heart failure survivors is a challenging task and helps medical professionals to make the right decisions about patients. Expertise and experience of medical professionals are required to care for heart failure patients. Machine Learning models can help with understanding symptoms of cardiac disease. However, manual feature engineering is challenging and requires expertise to select the appropriate technique. This study proposes a smart healthcare framework using the Internet-of-Things (IoT) and cloud technologies that improve heart failure patients' survival prediction without considering manual feature engineering. The smart IoT-based framework monitors patients on the basis of real-time data and provides timely, effective, and quality healthcare services to heart failure patients. The proposed model also investigates deep learning models in classifying heart failure patients as alive or deceased. The framework employs IoT-based sensors to obtain signals and send them to the cloud web server for processing. These signals are further processed by deep learning models to determine the state of patients. Patients' health records and processing results are shared with a medical professional who will provide emergency help if required. The dataset used in this study contains 13 features and was attained from the UCI repository known as Heart Failure Clinical Records. The experimental results revealed that the CNN model is superior to other deep learning and machine learning models with a 0.9289 accuracy value.


Altered patterns of gene expression distinguishing ascending aortic aneurysms from abdominal aortic aneurysms: complementary DNA expression profiling in the molecular characterization of aortic disease.
The purpose of this study was to profile altered patterns of gene expression that characterize degenerative ascending thoracic aortic aneurysms and to compare these patterns with those observed for infrarenal abdominal aortic aneurysms. Full-thickness aortic wall tissues were obtained during surgical repair of degenerative thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms (n = 4 each), with normal thoracic and abdominal aortas from organ transplant donors used as control preparations. Radiolabeled complementary DNA was prepared for each specimen and hybridized to complementary DNA microarrays, and differential levels of gene expression between aneurysmal and normal aortic tissues at each site were assessed by parametric statistics. Of 1185 genes examined, 112 (9.5%) were differentially expressed (P <.05) between thoracic aortic aneurysms and normal thoracic aorta, with 105 increased and 7 decreased. There were 104 genes (8.8%) differentially expressed between infrarenal abdominal aortic aneurysms and normal abdominal aorta (65 increased and 39 decreased). Quantitative increases in expression for 97 genes were unique to thoracic aortic aneurysms, whereas increases for 61 genes were unique to infrarenal abdominal aortic aneurysms. Although 8 gene products were significantly altered in both thoracic and infrarenal abdominal aortic aneurysms, these changes were directionally concordant for only 4 (matrix metalloproteinase 9/gelatinase B, v-yes-1 oncogene, mitogen-activated protein kinase 9, and intercellular adhesion molecule 1/CD54). Results for 9 genes were independently confirmed by quantitative reverse transcriptase-polymerase chain reaction. Thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms exhibit distinct patterns of gene expression relative to normal aorta from the same sites, with most alterations being unique to each disease. Degenerative aneurysms arising in different locations are thus characterized by a high degree of molecular heterogeneity, reflecting different pathophysiologic mechanisms.


Protein intrinsic disorder toolbox for comparative analysis of viral proteins.
To examine the usefulness of protein disorder predictions as a tool for the comparative analysis of viral proteins, a relational database has been constructed. The database includes proteins from influenza A and HIV-related viruses. Annotations include viral protein sequence, disorder prediction, structure, and function. Location of each protein within a virion, if known, is also denoted. Our analysis reveals a clear relationship between proximity to the RNA core and the percentage of predicted disordered residues for a set of influenza A virus proteins. Neuraminidases (NA) and hemagglutinin (HA) of major influenza A pandemics tend to pair in such a way that both proteins tend to be either ordered-ordered or disordered-disordered by prediction. This may be the result of these proteins evolving from being lipid-associated. High abundance of intrinsic disorder in envelope and matrix proteins from HIV-related viruses likely represents a mechanism where HIV virions can escape immune response despite the availability of antibodies for the HIV-related proteins. This exercise provides an example showing how the combined use of intrinsic disorder predictions and relational databases provides an improved understanding of the functional and structural behaviour of viral proteins.


Tuning lanthanide reactivity towards small molecules with electron-rich siloxide ligands.
The synthesis, structure, and reactivity of stable homoleptic heterometallic LnL4K2 complexes of divalent lanthanide ions with electron-rich tris(tert-butoxy)siloxide ligands are reported. The [Ln(OSi(OtBu)3)4K2] complexes (Ln=Eu, Yb) are stable at room temperature, but they promote the reduction of azobenzene to yield the KPhNNPh radical anion as well as the reductive cleavage of CS2 to yield CS3(2-) as the major product. The Eu(III) complex of the radical anion PhNNPh is structurally characterized. Moreover, [Yb(OSi(OtBu)3)4K2] can reduce CO2 at room temperature. Release of the reduction products in D2O shows the quantitative formation of both oxalate and carbonate in a 1:2.2 ratio. The bulky siloxide ligands enforce the labile binding of the reduction products providing the opportunity to establish a closed synthetic cycle for the Yb(II)-mediated CO2 reduction. These studies show that the presence of four electron-rich siloxide ligands renders their Eu(II) and Yb(II) complexes highly reactive.


A pilot study of the safety and tolerability of etanercept in patients with alcoholic hepatitis.
Alcoholic hepatitis is a cause of major morbidity and mortality, and effective therapeutic regimens to treat this condition are lacking. Both experimental and clinical evidence indicates that tumor necrosis factor alpha (TNF), and the downstream cytokine interleukin-6 (IL-6), correlate with disease severity and may contribute to the pathogenesis and clinical sequelae of alcoholic hepatitis, thereby implicating a possible role for inhibition of TNF in the treatment of alcoholic hepatitis. The aim of the current study was to assess the safety and tolerability of a p75-soluble TNF receptor:FC fusion protein (etanercept), an agent that binds and neutralizes soluble TNF in patients with alcoholic hepatitis in the form of an open-label pilot trial. Etanercept administration was targeted for 2 wk duration in 13 patients with moderate or severe alcoholic hepatitis as assessed by a discriminant function value greater than 15 and/or the presence of spontaneous hepatic encephalopathy. On an intention-to-treat basis, the 30-day survival rate of patients receiving etanercept was 92% (12/13). Adverse events that were encountered included infection, hepatorenal decompensation, and GI bleeding, which required premature discontinuation of etanercept in 23% of patients (3/13). This is the first study to examine TNF inhibition with etanercept in patients with alcoholic hepatitis and the results of this study support the rationale for larger controlled studies to further assess safety and efficacy.


Tracheal ultrasonography and ultrasonographic lung sliding for confirming endotracheal tube placement: Speed and Reliability.
In this study we aimed to evaluate the success of ultrasonography (USG) for confirming the tube placement and timeliness by tracheal USG and ultrasonographic lung sliding in resuscitation and rapid sequence intubation. This study was a prospective, single-center, observational study conducted in the emergency department of a tertiary care hospital. Patients were prospectively enrolled in the study. Patients who went under emergency intubation because of respiratory failure, cardiac arrest or severe trauma included in the study. Patients with severe neck trauma, neck tumors, history of neck operation or tracheotomy and under 18years old were excluded from the study. A total of 115 patients included in the study. The mean age was 67.2±17.1 with age 16-95years old. Among 115 patients 30 were cardiac arrest patients other 85 patients were non-cardiac arrest patients intubated with rapid sequence intubation. The overall accuracy of the ultrasonography was 97.18% (95% CI, 90.19-99.66%), and the value of kappa was 0.869 (95% CI, 0.77-0.96), indicating a high degree of agreement between the ultrasonography and capnography. The ulrasonography took significantly less time than capnography in total. Ultrasonography achieved high sensitivity and specificity for confirming tube placement and results faster than end-tidal carbon dioxide. Ultrasonography is a good alternative for confirming the endotracheal tube placement. Future studies should examine the use of ultrasonography as a method for real-time assessment of endotracheal tube placement by emergency physicians with only basic ultrasonographic training.


Self-assembly of organic monolayers onto hydrogen-terminated silicon: 1-alkynes are better than 1-alkenes.
Recently, a new method for the preparation of high-quality organic monolayers with 1-alkynes at room temperature in the dark (i.e., without any external activation) was reported. To pinpoint the precise origin of this self-assembly process and to compare the reactivity of 1-alkenes and 1-alkynes toward hydrogen-terminated Si(111) [H-Si(111)], we followed the gradual formation of both monolayers at room temperature by static water contact angle measurements. Subsequently, attenuated total reflection infrared spectroscopy (ATR-IR) and X-ray photoelectron spectroscopy (XPS) were used to obtain detailed information about the structure and quality of the resulting monolayers. Our data clearly demonstrate that 1-alkynes are considerably more reactive toward H-Si(111) than 1-alkenes. 1-Alkynes are able to self-assemble into densely packed hydrophobic monolayers without any external activation (i.e., at room temperature under ambient light and even in the dark) whereas for 1-alkenes under the same conditions hardly any reactivity toward H-Si(111) was observed. The self-assembly of 1-alkynes on H-Si(111) at room temperature is explained by three factors: the higher nucleophilicity of 1-alkynes, which results in a facile attack at the electron-hole pairs at the H-Si surface and easy Si-C bond formation, the stabilization of the beta radical by delocalization over the double bond, and the lower-energy barrier encountered for H abstractions.


Myopathy and fatal cardiopathy due to cytochrome c oxidase deficiency.
A 3-day-old girl had a syndrome of lethargy and lactic acidosis. Pregnancy and delivery had been normal; there was no consanguinity or family history of neuromuscular disease. At age 4 1/2 months, she had generalized weakness, hypotonia, areflexia, and macroglossia. She developed cyanosis and respiratory failure, and marked cardiomegaly was noted. She died at age 8 1/2 months of cardiac arrest. Results from a muscle biopsy specimen obtained at age 4 1/2 months showed ragged-red fibers and increased glycogen and lipid droplets. With the cytochrome c oxidase reaction, only 5% of the fibers stained positively in the biopsy specimen. Cytochrome c oxidase activity was 7.3% of normal in muscle mitochondria and 12.2% of normal in heart mitochondria. Reduced-minus-oxidized cytochrome spectra showed lack of the cytochrome aa3 peak. Immunotitration using antibodies against purified human heart cytochrome c oxidase showed normal amount of cross-reacting material in both heart and muscle. The genetic error could have involved a cytochrome c oxidase isozyme common to heart and muscle.


Locus encoding a family of small heat shock genes in Caenorhabditis elegans: two genes duplicated to form a 3.8-kilobase inverted repeat.
The genes coding for hsp 16-48, previously identified by cDNA cloning, and for another 16-kilodalton heat shock protein designated hsp16-1 were characterized by DNA sequencing. The two genes were arranged in a head-to-head orientation. Both the coding and flanking regions were located within a 1.9-kilobase module which was duplicated exactly to form a 3.8-kilobase inverted repeat structure. The inverted repeat structure ended in an unusual guanine-plus-cytosine-rich sequence 24 nucleotides in length. The identity of the two modules at the nucleotide sequence level implies that the duplication event may have occurred recently. Alternatively, gene conversion between the two modules could also maintain homology of the two gene pairs. The small heat shock genes of Caenorhabditis elegans contained TATA boxes and heat-inducible promoters, the latter agreeing closely with the Drosophila melanogaster consensus sequence described by Pelham (Cell 30:517-528, 1982). Unlike the homologous D. melanogaster genes, each of these C. elegans genes contained a short intron, the position of which has been conserved in a related murine alpha-crystallin gene. The intron separated variable and conserved regions within the amino acid sequences of the encoded heat shock polypeptides.


Routine parathyroid autotransplantation during total thyroidectomy: a procedure with predictable outcome.
To compare parathyroid gland autotransplantation with parathyroid gland preservation in situ with respect to the preservation of parathyroid gland function in patients undergoing total thyroidectomy. The quasi-experimental study was performed from July 1998 to June 2009 at the Khyber Teaching Hospital, Peshawar, Pakistan. A total of 388 patients underwent total thyroidectomy for a variety of thyroid gland disorders. They were divided into two groups; 97 patients in Group A had parathyroid glands preserved in situ, while 291 patients in Group B had at least one parathyroid gland autotransplanted in ipsilateral sternocleidomastoid muscle. Both groups were followed for six months for the assessment of parathyroid function. Fisher's exact test was used for comparison between the two groups. The mean age of Group A was 42.46 +/- 15.30 years, while in Group B it was 39.16 +/- 18.91 years. Overall male-to-female ratio was 1:3.5. In Group A, 3 (3.09%) patients developed permanent hypocalcaemia while in Group B only 1 (0.34%) patient developed permanent hypocalcaemia. Autotransplantation of at least one parathyroid gland after total thyroidectomy is a procedure with predictable outcome associated with minimal risk of permanent hypoparathyroidism.


Alteration of hepatic glycogen synthase phosphatase activity by insulin deficiency.
Perfused livers from normal and alloxan-diabetic rats were studied to determine whether the diabetes-related decrease in glycogen synthase phosphatase was due to an alteration of the synthase molecule, an increase in synthase phosphatase activity inhibition by phosphorylase a, or generation of inhibitor of the phosphatase. With purified rat liver synthase as substrate for the phosphatase, the diabetic tissue remained 90-95% deficient in the ability to catalyze synthase D to I conversion, showing that the defect cannot be solely due to an altered substrate. When synthase phosphatase assays were carried out in the presence of rat liver glycogen phosphorylase antiserum, phosphatase activity remained 70-75% deficient in diabetic tissue. Therefore, the defect cannot be attributed to increased inhibition of synthase phosphatase by increased amounts of phosphorylase a. When synthase phosphatase assays were run by mixing extracts from normal and diabetic livers, phosphatase activity was additive, indicating that a phosphatase inhibitor was probably not involved in the phosphatase deficiency in the diabetic. These data are consistent with the hypothesis that the diabetes-related defect in glucose regulation of hepatic glycogen synthase is due to a molecular alteration or a deficiency of a specific glycogen synthase phosphatase.


[Hashimoto encephalopathy--a difficult differential diagnosis. A case report of reversible dementia and psychosis].
Hashimoto encephalopathy is a rare disease that is associated with Hashimoto thyreoiditis. Dementia, disturbances of consciousness and epileptic seizures are the most common features. We report a case of Hashimoto encephalopathy in a 74-year-old woman who presented with psychotic episodes, visual hallucinations, dementia, tremor, rigidity and fluctuation of consciousness. After treatment with steroids, cognitive function became normal and other symptoms improved significantly. Hashimoto encephalopathy should be considered as a differential diagnosis of psychosis in combination with dementia and other neurological symptoms to dementia with Lewy bodies and Creutzfeldt-Jakob disease.


Maintenance IV immunoglobulin treatment in chronic inflammatory demyelinating polyradiculoneuropathy.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients treated with intravenous immunoglobulin (IVIg) usually start with a standard dosage of 2 g/kg bodyweight. Only a minority of patients has a sustained improvement, and most require ongoing maintenance treatment. Preferred IVIg regimens, however, vary considerably between doctors and at present it is unknown which is optimal. As there are also large differences in IVIg dosage and interval requirements between patients, optimal IVIg maintenance treatment of CIDP is even more complex. The lack of evidence-based guidelines on how IVIg maintenance treatment should be administered may potentially lead to under- or overtreatment of this expensive therapy. We provide an overview of published practical IVIg maintenance treatment regimens, IVIg maintenance schedules used in randomized controlled trials and one based upon our own long-term experience on how this treatment could be given in CIDP.


Multicentre validation of a EUCAST method for the antifungal susceptibility testing of microconidia-forming dermatophytes.
Terbinafine resistance is increasingly reported in Trichophyton, rendering susceptibility testing particularly important in non-responding cases. We performed a multicentre evaluation of six EUCAST-based methods. Ten laboratories susceptibility tested terbinafine, itraconazole, voriconazole and amorolfine against a blinded panel of 38 terbinafine WT and target gene mutant isolates. E.Def 9.3.1 modifications included: medium with/without addition of chloramphenicol and cycloheximide (CC), incubation at 25°C to 28°C for 5-7 days and three MIC endpoints [visually and spectrophotometrically (90%/50% inhibition)], generating 7829 MICs. Quality control (QC) strains were Aspergillus flavus ATCC 204304 and CNM-CM1813. Eyeball, ECOFFinder (where ECOFF stands for epidemiological cut-off) and derivatization WT upper limits (WT-ULs), very major errors (VMEs; mutants with MICs ≤WT-ULs) and major errors (MEs; WT isolates with MICs >WT-ULs) were determined. MICs fell within the QC ranges for ATCC 204304/CNM-CM1813 for 100%/96% (voriconazole) and 84%/84% (itraconazole), respectively. Terbinafine MICs fell within 0.25-1 mg/L for 96%/92%, suggesting high reproducibility. Across the six methods, the number of terbinafine MEs varied from 2 to 4 (2.6%-5.2%) for Trichophyton rubrum and from 0 to 2 (0%-2.0%) for Trichophyton interdigitale. Modes for WT and mutant populations were at least seven 2-fold dilutions apart in all cases. Excluding one I121M/V237I T. rubrum mutant and two mixed WT/mutant T. interdigitale specimens, the numbers of VMEs were as follows: T. rubrum: CC visual, 1/67 (1.5%); CC spectrophotometric 90% inhibition, 3/59 (5.1%); and CC spectrophotometric 50% inhibition, 1/67 (1.5%); and T. interdigitale: none. Voriconazole and amorolfine MICs were quite uniform, but trailing growth complicated determination of itraconazole visual and spectrophotometric 90% inhibition MIC. Although none of the laboratories was experienced in dermatophyte testing, error rates were low. We recommend the CC spectrophotometric 50% inhibition method and provide QC ranges and WT-ULs for WT/non-WT classification.


Numerical analysis of hip fracture due to a sideways fall.
The primary purpose of this paper is to outline a methodology for evaluating the likelihood of cortical bone fracture in the proximal femur in the event of a sideways fall. The approach includes conducting finite element (FE) analysis in which the cortical bone is treated as an anisotropic material, and the admissibility of the stress field is validated both in tension and compression regime. In assessing the onset of fracture, two methodologies are used, namely the Critical Plane approach and the Microstructure Tensor approach. The former is employed in the tension regime, while the latter governs the conditions at failure in compression. The propagation of localized damage is modeled using a constitutive law with embedded discontinuity (CLED). In this approach, the localized deformation is described by a homogenization procedure in which the average properties of cortical tissue intercepted by a macrocrack are established. The key material properties governing the conditions at failure are specified from a series of independent material tests conducted on cortical bone samples tested at different orientations relative to the loading direction. The numerical analysis deals with simulations of experiments involving the sideways fall, and the results are compared with the experimental data. This includes both the evolution of fracture pattern and the local load-displacement characteristics. The proposed approach is numerically efficient, and the results do not display a pathological mesh-dependency. Also, in contrast to the XFEM approach, the analysis does not require any extra degrees of freedom.


[Assessment of Nanophyetus salmincola schikhobalowl (Skrjiabin et Podjiapolskaja, 1931) infestation of salmonlike fishes in the rivers of the Khabarovsk Territory].
Parasitological investigations of 529 specimens of 7 fish species from the water basins of the Khabarovsk Territory in 2009-2013 revealed the high extensity (11.7 to 100%) and intensity (as many as 9341 larvae per fish) of invasion with N. s. schikhobalowi metacercaria in salmonlike fishes from the mountain tributaries (Khor, Anyui, and Manoma) of the Amur river. The examined specimens of four salmonlike fish species (Thymallus tugarinae, Hucho taimen, Brachymystax tumensis and B. lenok) showed an increase in all indicators of infestation: invasion extensity (IE), invasion intensity (II), and abundance index (AI) with age. Moreover, IE peaked just in a 3-4-year-old fish (and in 1-year-old B. lenok) and further remained virtually unchanged. N. s. schikhobalowi metacercaria accumulated in the fish trunk with age, by maintaining their viability. With very high II, practically 100% infestation in B. lenok makes the population run the maximum risk of Nanophyetus infection with the dietary intake of this fish species if it is not disinfected. Examination of the distribution of N. s. schikhobalowi metacercaria in the trunk of Thymallus tugarinae showed that over 50% of larvae were detectable in the kidneys. This peculiarity of their localization could propose a simple method to determine II for Nanophyetus larvae in salmonlike fishes. Recommendations for reducing the risk of human infection with trematodes are given.


Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia.
Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. An adult female proband with hypoalphalipoproteinemia, corneal opacity and mild anemia, as well as her first-degree relatives, were recruited for clinical, biochemical, genetic, in-silico and in-vitro LCAT analysis. Sequencing of exons and intron-exon boundaries was performed to identify mutations. Site-directed mutagenesis was carried out to generate plasmids containing cDNA with wild type or mutant sequences. Such expression vectors were transfected to HEK-239 T cells to asses the effect of LCAT variants in expression, synthesis, secretion and enzyme activity. In-silico prediction analysis and molecular modeling was also used to evaluate the effect of LCAT variants. LCAT sequencing identified rare p.V333 M and p.M404 V missense mutations in compound heterozygous state in the proband, as well the common synonymous p.L363 L variant. LCAT protein was detected in proband's plasma, but with undetectable enzyme activity compared to control relatives. HEK-293 T transfected cells with vector expression plasmids containing either p.M404 V or p.V333 M cDNA showed detectable LCAT protein expression both in supernatants and lysates from cultured cells, but with much lower enzyme activity compared to cells transfected with the wild-type sequence. Bioinformatic analyses also supported a causal role of such rare variations in LCAT lack of function. Additionally, the proband carried the minor allele of the synonymous p.L363 L variant. However, this variant is unlikely to affect the clinical phenotype of the proband given its relatively high frequency in the Chilean population (4%) and its small putative effect on plasma HDL-cholesterol levels. Genetic, biochemical, in vitro and in silico analyses indicate that the rare mutations p.M404 V and p.V333 M in LCAT gene lead to suppression of LCAT enzyme activity and cause clinical features of familial LCAT deficiency.


Adenosine and hypoxia effects on atrioventricular node of adult and neonatal rabbit hearts.
An isolated perfused heart model was used to assess the effects of hypoxia and adenosine on the adult and neonatal (1-5 days) rabbit atrioventricular (AV) node. The AV nodal function was assessed by the A-H interval at a constant atrial pacing cycle length and by the longest pacing cycle length resulting in Wenckebach periodicity. We defined the pacing cycle length at or below which the AV node demonstrated Wenckebach periodicity as the Wenckebach cycle length. Adenosine produced a smaller dose-dependent increase in A-H interval in neonates than in adults, but the increase in Wenckebach cycle length was similar in the two age groups. When the hearts were exposed to 5 min of hypoxia the increase of Wenckebach cycle length was greater for adults than for neonates. The change in Wenckebach cycle length in adults caused by hypoxia was significantly greater than that caused by 1 mM adenosine. In addition, in adults aminophylline could partially attenuate the increase in Wenckebach periodicity caused by adenosine, but aminophylline could not attenuate the increase in Wenckebach cycle length caused by hypoxia. We conclude that in the rabbit AV node 1) the adenosine effect in neonates is similar to that in adults; 2) neonates are relatively resistant to acute hypoxia compared with adults; and 3) the response to acute hypoxia in adults cannot be totally explained by the adenosine release theory.


Identification of diverse modulators of central and peripheral circadian clocks by high-throughput chemical screening.
The circadian clock coordinates daily oscillations of essential physiological and behavioral processes. Conversely, aberrant clocks with damped amplitude and/or abnormal period have been associated with chronic diseases and aging. To search for small molecules that perturb or enhance circadian rhythms, we conducted a high-throughput screen of approximately 200,000 synthetic compounds using Per2lucSV reporter fibroblast cells and validated 11 independent classes of molecules with Bmal1:luciferase reporter cells as well as with suprachiasmatic nucleus and peripheral tissue explants. Four compounds were found to lengthen the period in both central and peripheral clocks, including three compounds that inhibited casein kinase Iε in vitro and a unique benzodiazepine derivative acting through a non-GABA(A) receptor target. In addition, two compounds acutely induced Per2lucSV reporter bioluminescence, delayed the rhythm, and increased intracellular cAMP levels, but caused rhythm damping. Importantly, five compounds shortened the period of peripheral clocks; among them, four compounds also enhanced the amplitude of central and/or peripheral reporter rhythms. Taken together, these studies highlight diverse activities of drug-like small molecules in manipulating the central and peripheral clocks. These small molecules constitute a toolbox for probing clock regulatory mechanisms and may provide putative lead compounds for treatment of clock-associated diseases.


Preparation of iron oxide nanoparticles by microwave synthesis and their characterization.
In this study production of fine particle Fe2O3 via microwave processing of Fe(NO3)3.nH2O followed by low temperature annealing was reported. XRD was used to characterize the structural properties of nanoparticles. Approximate particle sizes were between 3-13 nm according to Scherrer's equation. Single point BET measurement results also show that samples have large surface area and they are nanometer sized particles. TEM study was conducted to examine the structure of the nanoparticles. TEM figure is in good agreement with the results obtained from Scherrer's equation using XRD spectra. In order to characterize the magnetic properties of the nanoparticles VSM (Vibrating Sample Magnetometer) was used. From these results it can be concluded that the sample containing only maghemite phase exhibits superparamagnetic behaviour, on the other hand sample containing both hematite and maghemite phases shows paramagnetic behaviour above 300 K, superparamagnetic behavior at lower temperatures.


Reduction of methane and nitrogen emission and improvement of feed efficiency, rumen fermentation, and milk production through strategic supplementation of eucalyptus (Eucalyptus citriodora) leaf meal in the diet of lactating buffalo (Bubalus bubalis).
Buffalo plays a compelling role in reducing malnutrition and ensuring food to the people of Asian countries by its major contribution to milk and meat pool of the livestock agriculture farming system in the region. As Asia is the home for more than 90% of world buffalo population, they are also one of the largest emitters of greenhouse gasses. Eucalyptus (Eucalyptus sp.) leaves are rich sources of naturally occurring essential oils and phenolic compounds, which could modulate rumen fermentation through mitigation of methanogenesis and nitrogen excretion along with stimulation of immune system and production performances of animals. Therefore, the present study investigated the impact of dietary inclusion of eucalyptus (Eucalyptus citriodora) leaf meal (ELM) on voluntary feed intake, rumen functions, methane emission, nutrient utilization, milk yield and fatty acids profile, and immune response in lactating buffalo (Bubalus bubalis). An in vitro experiment conducted with graded dose (10-40 g/kg) inclusion of ELM into the total mixed ration to select ideal level for feeding to lactating buffaloes, an improvement (P < 0.05) in feed degradability (IVDMD), microbial biomass and ruminal volatile fatty acids concentration with reduced (P < 0.05) methane and ammonia-N production were evidenced when ELM was added at 10-20 g/kg DM, beyond which negative effects on rumen fermentation were pronounced. An in vivo experimentation was conducted with sixteen Murrah (Bubalus bubalis) buffaloes of mean live weight, 544.23 ± 10.02 kg; parity, 2-4 at initial stage (~60 days) of lactation with average milk yield of 11.43 ± 1.32 kg and were divided into two groups (CON, ELM) of eight each in a completely randomized design. All the animals were kept individually on wheat straw-based diet with required quantity of concentrate mixture and green fodder. The control group buffaloes were fed a total mixed ration; however, the treatment group (ELM) was supplemented with 10 g/kg DM diet of dry grounded eucalyptus (Eucalyptus citriodora) leaves by mixing with the concentrate mixture. The feeding experiment was conducted for 120 days, including 15 days for adaptation to the experimental diets and 105 days for data recording. The nutrient digestibility (DM, OM, CP, and EE) was improved (P < 0.05) without affecting feed intake (P > 0.05) and fiber digestibility (NDF and ADF) in ELM supplemented buffaloes. Increased (P < 0.05) milk production and rumenic acid concentration (cis 9 trans 11 C18:2 CLA) were demonstrated with comparable (P > 0.05) milk composition and major fatty acids profile of milk in the supplemented buffaloes. Dietary inclusion of ELM reduced (P < 0.05) enteric methane production and fecal excretion of nitrogen. The health status of buffaloes fed ELM improved throughout the experimental period was improved by enhancing cell mediated (P = 0.09) and humoral (P < 0.01) immune responses without affecting (P > 0.05) major blood metabolites. The study described feeding ELM at 10 g/kg diet to lactating Murrah buffaloes as a natural source of phenols and essential oils to increase milk production and CLA content, reduce methane and nitrogen emissions, and improve health status. Thus, feeding of ELM could be beneficial for climate smart buffalo production system for enhancing milk production with lesser impact on environment.


A model explaining declining rate in hydrolysis of lignocellulose substrates with cellobiohydrolase I (cel7A) and endoglucanase I (cel7B) of Trichoderma reesei.
It is commonly observed that the rate of enzymatic hydrolysis of solid cellulose substrates declines markedly with time. In this work the mechanism behind the rate reduction was investigated using two dominant cellulases of Trichoderma reesei: exoglucanase Cel7A (formerly known as CBHI) and endoglucanase Cel7B (formerly EGI). Hydrolysis of steam-pretreated spruce (SPS) was performed with Cel7A and Cel7B alone, and in reconstituted mixtures. Throughout the 48-h hydrolysis, soluble products, hydrolysis rates, and enzyme adsorption to the substrate were measured. The hydrolysis rate for both enzymes decreases rapidly with hydrolysis time. Both enzymes adsorbed rapidly to the substrate during hydrolysis. Cel7A and Cel7B cooperate synergistically, and synergism was approximately constant during the SPS hydrolysis. Thermal instability of the enzymes and product inhibition was not the main cause of reduced hydrolysis rates. Adding fresh substrate to substrate previously hydrolyzed for 24 h with Cel7A slightly increased the hydrolysis of SPS; however, the rate increased even more by adding fresh Cel7A. This suggests that enzymes become inactivated while adsorbed to the substrate and that unproductive binding is the main cause of hydrolysis rate reduction. The strongest increase in hydrolysis rate was achieved by adding Cel7B. An improved model is proposed that extends the standard endo-exo synergy model and explains the rapid decrease in hydrolysis rate. It appears that the processive action of Cel7A becomes hindered by obstacles in the lignocellulose substrate. Obstacles created by disordered cellulose chains can be removed by the endo activity of Cel7B, which explains some of the observed synergism between Cel7A and Cel7B. The improved model is supported by adsorption studies during hydrolysis.


[Asymptomatic chronic intrahepatic cholestasis and multiple hypodense nodules in the liver and the spleen: manifestations of a case of sarcoidosis].
Sarcoidosis is a systemic granulomatous disease of unknown etiology which may present multiple clinical manifestations. Liver involvement is observed among 21-79% of the cases. Nonetheless, hepatic sarcoidosis is usually asymptomatic and the finding of cholestasis is an infrequent complication. In the last few years, the presence of multiple hypodense nodules in the liver and spleen has been described in 5-15% of these patients following the application of dynamic intravenous techniques in abdominal CT scan. Although the histopathologic study of these nodules suggests that their formation is due to the coalescence of the microscopic granulomas, the cause of this aggregation remains unknown. A case of hepatic sarcoidosis presenting chronic cholestasis and whose abdominal tomographic study with intravenous contrast demonstrated the existence of hypodense lesions in the liver and spleen suggesting malignant disseminated disease is reported.


Active control of transmission loss with smart foams.
Smart foams combine the complimentary advantages of passive foam material and spatially distributed piezoelectric actuator embedded in it for active noise control applications. In this paper, the problem of improving the transmission loss of smart foams using active control strategies has been investigated both numerically and experimentally inside a waveguide under the condition of plane wave propagation. The finite element simulation of a coupled noise control system has been undertaken with three different smart foam designs and their effectiveness in cancelling the transmitted wave downstream of the smart foam have been studied. The simulation results provide insight into the physical phenomenon of active noise cancellation and explain the impact of the smart foam designs on the optimal active control results. Experimental studies aimed at implementing the real-time control for transmission loss optimization have been performed using the classical single input/single output filtered-reference least mean squares algorithm. The active control results with broadband and single frequency primary source inputs demonstrate a good improvement in the transmission loss of the smart foams. The study gives a comparative description of the transmission and absorption control problems in light of the modification of the vibration response of the piezoelectric actuator under active control.


Precision metrology.
This article is a summary of the Satellite Meeting, which followed on from the Discussion Meeting at the Royal Society on 'Ultra-precision engineering: from physics to manufacture', held at the Kavli Royal Society International Centre, Chicheley Hall, Buckinghamshire, UK. The meeting was restricted to 18 invited experts in various aspects of precision metrology from academics from the UK and Sweden, Government Institutes from the UK and Germany and global aerospace industries. It examined and identified metrology problem areas that are, or may be, limiting future developments in precision engineering and, in particular, metrology. The Satellite Meeting was intended to produce a vision that will inspire academia and industry to address the solutions of those open-ended problems identified. The discussion covered three areas, namely the function of engineering parts, their measurement and their manufacture, as well as their interactions.


Local structural and functional MRI markers of compulsive behaviors and obsessive-compulsive disorder diagnosis within striatum-based circuits.
Obsessive-compulsive disorder (OCD) is a classic disorder on the compulsivity spectrum, with diverse comorbidities. In the current study, we sought to understand OCD from a dimensional perspective by identifying multimodal neuroimaging patterns correlated with multiple phenotypic characteristics within the striatum-based circuits known to be affected by OCD. Neuroimaging measurements of local functional and structural features and clinical information were collected from 110 subjects, including 51 patients with OCD and 59 healthy control subjects. Linked independent component analysis (LICA) and correlation analysis were applied to identify associations between local neuroimaging patterns across modalities (including gray matter volume, white matter integrity, and spontaneous functional activity) and clinical factors. LICA identified eight multimodal neuroimaging patterns related to phenotypic variations, including three related to symptoms and diagnosis. One imaging pattern (IC9) that included both the amplitude of low-frequency fluctuation measure of spontaneous functional activity and white matter integrity measures correlated negatively with OCD diagnosis and diagnostic scales. Two imaging patterns (IC10 and IC27) correlated with compulsion symptoms: IC10 included primarily anatomical measures and IC27 included primarily functional measures. In addition, we identified imaging patterns associated with age, gender, and emotional expression across subjects. We established that data fusion techniques can identify local multimodal neuroimaging patterns associated with OCD phenotypes. The results inform our understanding of the neurobiological underpinnings of compulsive behaviors and OCD diagnosis.


Effects of resistive breathing on exercise capacity and diaphragm function in patients with ischaemic heart disease.
Muscle weakness has been suggested to result from the deconditioning that accompanies decreased activity levels in chronic cardiopulmonary diseases. The benefits of standard exercise programmes on exercise capacity and muscular strength in disease and health are well documented and exercise capacity is a significant predictor of survival in patients with chronic heart failure (CHF). Selective respiratory muscle training has been shown to improve exercise tolerance in CHF and such observations have been cited to support the suggestion that respiratory muscle weakness contributes to a reduced exercise capacity (despite biopsies showing the metabolic profile of a well trained muscle). This study aimed to determine the effects of selective inspiratory muscle training on patients with chronic coronary artery disease to establish if an improved exercise capacity can be obtained in patients that are not limited in their daily activities. Nine male patients performed three exercise tests (with respiratory and diaphragm function assessed before the third test) then undertook a 4-week programme of inspiratory muscle training. Exercise tolerance, respiratory and diaphragmatic function were re-assessed after training. Exercise capacity improved from 812+/-42 to 864+/-49 s, P<0.05, and velocity of diaphragm shortening increased (during quiet breathing from 12.8+/-1.6 to 19.4+/-1.1 mm s(-1), P<0.005, and sniffing from 71.9+/-9.4 to 110.0+/-12.3 mm s(-1), P<0.005). In addition, five from nine patients were stopped by breathlessness before training; whereas only one patient was stopped by breathlessness after training. The major findings in this study were that a non-intensive 4-week training programme of resistive breathing in patients with chronic coronary artery disease led to an increase in exercise capacity and a decrease in dyspnoea when assessed by symptom limited exercise testing. These changes were associated with significant increases in the velocity of diaphragmatic excursions during quiet breathing and sniffing. Patients that exhibited small diaphragmatic excursions during quiet breathing were most likely to improve their exercise capacity after the training programme. However, the inspiratory muscle-training programme was not associated with any significant changes in respiratory mechanics when peak flow rate, forced expiratory volume and forced vital capacity were measured. The resistive breathing programme used here resulted in a significant increase in the velocity of diaphragm movement during quiet breathing and sniffing. In other skeletal muscles, speed of contraction can be determined by the relative proportion of fibre types and muscle length (Jones, Round, Skeletal Muscle in Health and Disease. Manchester: University Press, 1990). The intensity of the training programme used here, however, is unlikely to significantly alter muscle morphology or biochemistry. Short-term training studies have shown that there can be increases in strength and velocity of shortening that do not relate to changes in muscle biochemistry or morphology. These changes are attributed to the neural adaptations that occur early in training (Northridge et al., Br. Heart J. 1990; 64: 313-316). Independent of the mechanisms involved, this small, uncontrolled study suggests that inspiratory muscle training may improve exercise capacity, diaphragm function and symptoms of breathlessness in patients with chronic coronary artery disease even in the absence of heart failure.


Effect of bile acid conjugation pattern on bile acid metabolism in normal humans.
Six male subjects were fed taurine 0.5 g six times daily for 2 wk to determine the effect of a shift in bile acid conjugation pattern upon bile acid metabolism. Duodenal bile acids were analyzed, and bile acid pool size, daily fecal excretion, and biliary excretion rate were quantified. In addition, daily biliary excretion rate of cholesterol and phospholipid were quantified, and biliary saturation with cholesterol was estimated. The dose of taurine caused reversal of the bile acid glycine-to-taurine conjugation ratio. Total bile acid pool size decreased, as did the pool size of chenodeoxycholic acid. Pool sizes of cholic and deoxycholic acids did not change. Daily fecal bile acid excretion decreased slightly. Biliary secretion rates of cholesterol, phospholipid, and bile acids did not change, nor did biliary cholesterol saturation. Pool size can decrease because of increased bile acid catabolism or decreased synthesis. The fact that bile acid excretion failed to increase, and actually decreased slightly, suggests that the effect is upon bile acid synthesis. In normal humans, the effect is small and probably physiologically unimportant. In special cases, however, such as during ursodeoxycholic acid therapy, the effect of shifting conjugation pattern may become important.


Tumors about the knee misdiagnosed as athletic injuries.
Musculoskeletal tumors may originally mimic a traumatic condition, and, on the basis of an erroneous diagnosis of an athletic injury, an invasive diagnostic or therapeutic procedure may be performed. We determined the number of such cases treated at our institution, and we analyzed the initial and final diagnoses as well as the changes in the indicated oncologic surgical technique due to the initial erroneous diagnosis. Twenty-five patients who had a bone or soft-tissue tumor about the knee that originally had been diagnosed as an athletic injury were referred to our institution. The complete clinical, radiographic, and pathological records were reviewed. Studies that had been performed prior to the invasive procedure and at the time of admission to our institution were evaluated to determine differences in the tumor stage and the oncologic treatment that was indicated at each time. Of 667 knee tumors diagnosed in our institution, twenty-five (3.7%) previously had been treated with an intra-articular procedure as a result of a misdiagnosis of an athletic injury. The final diagnoses made at our institution were a benign tumor in eleven patients and a malignant tumor in fourteen. Oncologic surgical treatment was affected in fifteen of the twenty-five patients. When a knee tumor is initially misdiagnosed as an athletic injury, treatment may be adversely affected by the delay in diagnosis or an inappropriate invasive procedure that results in extension of the tumor. Initial poor-quality radiographs and an unquestioned original diagnosis despite persistent symptoms were the most frequent causes of an erroneous diagnosis.


Evidence-based Recommendations for the Management of Comorbidities in Rheumatoid Arthritis, Psoriasis, and Psoriatic Arthritis: Expert Opinion of the Canadian Dermatology-Rheumatology Comorbidity Initiative.
Comorbidities such as cardiovascular diseases (CVD), cancer, osteoporosis, and depression are often underrecognized in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis (PsO). Recommendations may improve identification and treatment of comorbidities. The Canadian Dermatology-Rheumatology Comorbidity Initiative reviewed the literature to develop practical evidence-based recommendations for management of comorbidities in patients with RA, PsA, and PsO. Eight main topics regarding comorbidities in RA, PsA, and PsO were developed. MEDLINE, EMBASE, and the Cochrane Library (1960-12/2012), together with abstracts from major rheumatology and dermatology congresses (2010-2012), were searched for relevant publications. Selected articles were analyzed and metaanalyses performed whenever possible. A meeting including rheumatologists, dermatologists, trainees/fellows, and invited experts was held to develop consensus-based recommendations using a Delphi process with prespecified cutoff agreement. Level of agreement was measured using a 10-point Likert scale (1 = no agreement, 10 = full agreement) and the potential effect of recommendations on daily clinical practice was considered. Grade of recommendation (ranging from A to D) was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels. A total of 17,575 articles were identified, of which 407 were reviewed. Recommendations were synthesized into 19 final recommendations ranging mainly from grade C to D, and relating to a large spectrum of comorbidities observed in clinical practice: CVD, obesity, osteoporosis, depression, infections, and cancer. Level of agreement ranged from 80.9% to 95.8%. These practical evidence-based recommendations can guide management of comorbidities in patients with RA, PsA, and PsO and optimize outcomes.