Characterization of grade 2 commercially pure Trabecular Titanium structures.
In this work, two different cellular solid structures, obtained by EBM using grade 2 Titanium powders, were investigated. Relative density was evaluated comparing different methods, the mean diameter of the singular open porosity was calculated by SEM image post-processing; the chemical composition was evaluated using Energy Dispersive X-Ray Spectroscopy (EDXS); the microstructure and grain dimension were investigated using chemical etching and, the mechanical properties were investigated using UMTS 810 Materials Test System. The mean porosity values resulted to be similar to spongy bone (around 77% for sample A and 89% for sample B). The mean diameter of the single porosity resulted to be 640 μm for A and 1250 μm for B. The Vickers microhardness results were homogeneous among the structure and the chemical etching showed a complex microstructure characterized by irregular shaped grains. Sample A, as expected, is more resistant than sample B, while sample B shows a lower elastic modulus.


Differences in the binding of drugs to plasma proteins from newborn and adult man. II.
The binding of certain drugs to isolated fractions of plasma proteins obtained from newborn and adult man has been studied by equilibrium dialysis. For thiopental, desipramine, nitrofurantoin, sulfamethoxydiazine, meticillin and salicylic acid no difference was found between binding to the albumin fraction from newborns and adults. However, for thiopental, desipramine and promethazine binding to the globulin fraction was smaller in the newborns than in adults. Addition of bilirubin to the albumin fraction decreased the binding of nitrofurantoin, sulfamethoxydiazine and meticillin. No difference in the binding of meticillin to the albumin or globulin fractions from newborns and adults was found. The binding decreased, however, if both fractions were combined. Four mechanisms to explain the difference in binding between newborns and adults are discussed: (1) Displacement of drugs by bilirubin, (2) different binding properties of cord and adult albumin, (3) different properties of the globulins and (4) interaction of albumin with globulins in the newborn.


De novo nucleotide biosynthetic pathway and cancer.
De novo nucleotide biosynthetic pathway is a highly conserved and essential biochemical pathway in almost all organisms. Both purine nucleotides and pyrimidine nucleotides are necessary for cell metabolism and proliferation. Thus, the dysregulation of the de novo nucleotide biosynthetic pathway contributes to the development of many human diseases, such as cancer. It has been shown that many enzymes in this pathway are overactivated in different cancers. In this review, we summarize and update the current knowledge on the de novo nucleotide biosynthetic pathway, regulatory mechanisms, its role in tumorigenesis, and potential targeting opportunities.


Memantine protects against amphetamine derivatives-induced neurotoxic damage in rodents.
We hypothesize that 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) interact with alpha-7 nicotinic receptors (nAChR). Here we examine whether memantine (MEM), an antagonist of NMDAR and alpha-7 nAChR, prevents MDMA and METH neurotoxicity. MEM prevented both serotonergic injury induced by MDMA in rat and dopaminergic lesion by METH in mice. MEM has a better protective effect in front of MDMA- and METH-induced neurotoxicity than methyllycaconitine (MLA), a specific alpha-7 nAChR antagonist. The double antagonism that MEM exerts on NMDA receptor and on alpha-7 nAChR, probably contributes to its effectiveness. MEM inhibited reactive oxygen species production induced by MDMA or METH in synaptosomes. This effect was not modified by NMDA receptor antagonists, but reversed by alpha-7 nAChR agonist (PNU 282987), demonstrating a preventive effect of MEM as a result of it blocking alpha-7 nAChR. In synaptosomes, MDMA decreased 5-HT uptake by about 40%. This decrease was prevented by MEM and by MLA but enhanced by PNU 282987. A similar pattern was observed when we measured the dopamine transport inhibited by METH. The inhibition of both transporters by amphetamine derivatives seems to be regulated by the calcium incorporation after activation of alpha-7 nAChR. MDMA competitively displaces [(3)H]MLA from rat brain membranes. MEM and METH also displace [(3)H]MLA with non-competitive displacement profiles that fit a two-site model. We conclude that MEM prevents MDMA and METH effects in rodents. MEM may offer neuroprotection against neurotoxicity induced by MDMA and METH by preventing the deleterious effects of these amphetamine derivatives on their respective transporters.


Characterization of a rabbit reticulocyte supernatant factor that reverses the translational inhibition of hemin deficiency.
The control of protein synthesis by hemin in rabbit reticulocyte lysate is mediated by the formation of a high molecular weight protein inhibitor (or translational repressor) of polypeptide chain initiation from a precursor (prorepressor), which acts by phosphorylating the Mr 35,000 (alpha) subunit of eIF-2. We originally isolated a post-ribosomal supernatant factor from reticulocyte lysate, distinct from soluble eIF-2, that could completely reverse the inhibition of protein synthesis that occurs when reticulocyte lysate is incubated in the absence of hemin. We have found that this supernatant factor promotes the inactivation of the intermediate form of the translational repressor (generated within 1 h of incubation of the prorepressor in the absence of hemin), but only in the presence of GTP. This inactivation is not seen with the irreversible form of the translational repressor (generated after prolonged incubation of the prorepressor) and does not occur with other nucleoside triphosphates, dGTP or GDP. In addition, the inactivation reaction is not dependent upon Mg2+ and is not mediated by cyclic GMP. When lysate samples were pulsed with [gamma-32P]ATP at 15 min of incubation, the addition of the supernatant factor at zero time or after 7 min was associated with preventing or reversing the phosphorylation of eIF-2 alpha. In contrast, another soluble reticulocyte protein termed reversing factor can be separated from the supernatant factor on phosphocellulose, partly overcomes the effect of the irreversible translational repressor, and is associated with increased phosphorylation of eIF-2 alpha.


Incidence of neuraxial haematoma after total hip or knee surgery: RECORD programme (rivaroxaban vs. enoxaparin).
Patients receiving anticoagulants could be at higher risk of compressive haematoma with neuraxial anaesthesia use. The phase III RECORD programme compared rivaroxaban with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement surgery in more than 12,500 patients. This observational analysis evaluated the risk of neuraxial haematoma after neuraxial anaesthesia in patients receiving rivaroxaban or enoxaparin using pooled RECORD1-4 data. The incidences of intraspinal bleeding or haemorrhagic puncture were recorded as part of the criteria for major bleeding (the primary safety outcome in the RECORD studies). Incidences of allogeneic transfusion and venous thromboembolism by type of anaesthesia were also recorded. No compressive haematomas occurred in rivaroxaban-treated patients (10 mg once daily started 6-8 h after surgery) who underwent neuraxial anaesthesia (n = 4086). Among enoxaparin-treated patients (n = 4090), one compressive spinal haematoma requiring laminectomy occurred after epidural catheter removal in an elderly female patient with renal insufficiency undergoing total knee replacement. Total venous thromboembolism rates did not differ according to type of anaesthesia. Although no issues were observed with the use of neuraxial anaesthesia in this population of 4086 patients receiving rivaroxaban after total hip or knee replacement, it is important to remain aware of the risk of compressive haematoma. This may be of particular concern in elderly patients with renal insufficiency receiving an anticoagulant predominantly eliminated via the kidneys.


Variability of pharmacokinetic parameters for contraceptive steroids.
Studies of the pharmacokinetics of three contraceptive steroids, ethynyloestradiol, norethisterone and norethisterone oenanthate, in large groups of women are reviewed. Extremely wide variations were observed between women in the various calculated pharmacokinetic parameters. Studies carried out in small groups of subjects may give misleading results. It is difficult to ascribe any meaning and interpretation to most of the derived values but they do provide a means of comparing aspects of the metabolism of the various steroids. It is difficult to relate the pharmacokinetic values to the various biological actions of the steroids. However, the wide variations between subjects in the pharmacokinetic parameters must indicate equally wide variations in the biological activity of the steroids. Subjects in whom the bio-availability is low or where the rate of metabolism is rapid might be expected to respond differently, both in terms of efficacy and side-effects, from subjects with high values for bio-availability and a slow metabolism.


Protective adaptive immunity to Chlamydophila abortus infection and control of ovine enzootic abortion (OEA).
Ovine enzootic abortion (OEA) remains a major problem in sheep-rearing countries despite the availability of protective vaccines. The causative agent, Chlamydophila abortus, is a Gram-negative bacterium that can induce a persistent, subclinical infection in non-pregnant sheep. The development of a new safe, effective and practical vaccine requires a detailed understanding of host-pathogen interactions and the identification of clear correlates of protection. Since disease (abortion) is only observed during pregnancy, the nature of host immunity to C. abortus and the specialised immunological features that permit maternal acceptance of the semi-allogeneic fetus are central to the pathogenesis of OEA. We review the current literature on persistence of C. abortus, host immunity to infection and mechanisms of abortion. We identify the key outstanding questions surrounding OEA and discuss the current knowledge gaps with a view to developing improved control strategies.


Extraction of the GVS electrical artifact from EEG recordings of the motor related cortical potential.
Galvanic vestibular stimulation (GVS) involves the administration of low-amplitude trans-mastoidal current which induces a dense electrical field across the scalp that is difficult to remove from the EEG record. In two proof-of-concept experiments, we designed a paradigm to evaluate functional limb movement, and tested a method of blind source separation to remove the scalp artifact induced by low-amplitude, alternating current GVS to allow measurement of the motor-related cortical response (MRCP) during voluntary movement. Off-line Extended Infomax Independent Component Analysis (ICA) was applied to the concatenated dataset to identify and remove core characteristics of the artifact induced by a trans-mastoidal current (Experiment 1: 0.01 Hz, 0.2-3 mA; Experiment 2: 0.01 Hz, 0.3-0.4 mA) during finger (Experiments 1 and 2) and foot tapping (Experiment 2). In Experiment 1, a GVS-related independent component was identified and successfully removed without compromising measurement of the MRCP. This success was replicated in Experiment 2 which included both finger and foot tapping, and a higher GVS amplitude, which resulted in the identification of additional GVS-related artifacts. Existing methods of artifact rejection typically use an offline bandpass filter that overlaps with the frequency range of the MRCP. Even when similar ICA-based approaches have been employed, they have been applied during rest rather than active movement, have not been described in sufficient detail to enable replication, and require significant expertise and bespoke software to implement. The ICA-based approach described here provides a relatively simple and accessible means by which MRCPs can be measured during alternating current GVS. This provides opportunity to identify new biomarkers associated with the therapeutic effects of GVS in people with Parkinson's disease and other disorders of voluntary movement.


Using different matrix factorization approaches to identify muscle synergy in stroke survivors.
Over the past several decades, many scholars have investigated muscle synergy as a promising tool for evaluating motor function. However, it is challenging to obtain favorable robustness using the general muscle synergy identification algorithms, namely non-negative matrix factorization (NMF), independent component analysis (ICA), and factor analysis (FA). Some scholars have proposed improved muscle synergy identification algorithms to overcome the shortcomings of these approaches, such as singular value decomposition NMF (SVD-NMF), sparse NMF (S-NMF), and multivariate curve resolution-alternating least squares (MCR-ALS). However, performance comparisons of these algorithms are seldom conducted. In this study, experimental electromyography (EMG) data collected from healthy individuals and stroke survivors were applied to assess the repeatability and intra-subject consistency of NMF, SVD-NMF, S-NMF, ICA, FA, and MCR-ALS. MCR-ALS presented higher repeatability and intra-subject consistencies than the other algorithms. More synergies and lower intra-subject consistencies were observed in stroke survivors than in healthy individuals. Thus, MCR-ALS is considered a favorable muscle synergy identification algorithm for patients with neural system disorders.


Avoiding exposure to air pollution by using filtering facemask respirators: An application of the health action process approach.
Adherence to the use of filtering facemask respirators on hazy days to reduce exposure to air pollution is examined with the aim of uncovering psychological mechanisms that may be responsible for individual differences in motivation and behavior. In a longitudinal survey, 164 young adults from Beijing, China, completed assessments at baseline (Time 1), 2 weeks (Time 2), and 4 weeks later (Time 3). Self-efficacy, risk perception, and outcome expectancies were measured along with intention at Time 1, planning and action control at Time 2, and facemask use at Time 3. A structural equation model was specified to test theory-implied pathways of influence. Self-efficacy and risk perception jointly predicted behavioral intention at Time 1. Planning and action control at Time 2 jointly predicted behavior at Time 3, serving as parallel mediators between intention (Time 1) and facemask use (Time 3). The model explained 19.5% and 30.2% of the variance in intention and behavior, respectively. Results support theory-based psychological mechanisms, with a focus on planning and action control, which might be influential in the adoption and maintenance of self-protective facemask wearing.


Fast and reversible response of thylakoid-associated polyamines during and after UV-B stress: a comparative study of the wild type and a mutant lacking chlorophyll b of unicellular green alga Scenedesmus obliquus.
The functional and biochemical aspects of the photosynthetic apparatus in response to UV-B radiation were examined in unicellular oxygenic algae Scenedesmus obliquus. The wild type (Wt) and a chlorophyll b-less mutant (Wt-lhc) were used as a specific tool for the understanding of antenna role. Photosynthesis was monitored during and after UV-B stress by time resolved fluorescence spectroscopy and polarography. Carotenoids, such as neoxanthin, loroxanthin, lutein, violaxanthin, antheraxanthin, zeaxanthin, alpha- and beta-carotene, cellular and thylakoid-associated putrescine, spermidine, spermine and subcomplexes of light-harvesting complex (LHCII) of photosystem II (PSII) were investigated to assess their possible involvement in response to UV-B. Oxygen evolution depression by UV-B was higher in the Wt-lhc mutant than in the Wt. Photosynthesis recovery occurred in the Wt, but not in the mutant. The dissipation of excess excitation energy during UV-B stress was accompanied by changes in the thylakoid-associated polyamines which were much higher than changes in xanthophylls. We conclude that, at least in the unicellular green alga S. obliquus, mutants lacking chlorophyll b have significant lower capacity for recovery after UV-B stress. In addition, the comparison of xanthophylls and thylakoid-associated polyamines reveals that the latter are more responsive to UV-B stress and in a reversible manner.


Textbook Outcomes After Open Live Donor Right Hepatectomy and Open Right Hepatic Lobectomy for Cancer in 686 patients: Redefining the Benchmark.
To compare textbook outcomes (TO) of open live donor right hepatectomy (RH) versus open right hepatic lobectomy for cancer in a single Western center and to identify clinical factors associated with failure to achieve a TO. TO, a composite quality measure that captures multiple aspects of perioperative care, has not been thoroughly studied in open RH. We hypothesized that TO rates after RH for live donor transplant could represent the "best-achievable" results of this operation and could serve as the benchmark for RH performed for an oncologic indication. A prospective database was reviewed to compare TO rates after RH for live donor purposes versus RH for cancer at a single center from 2010 to 2020. A TO was defined as achieving 7 metrics: no perioperative transfusion, no major postoperative complications, no significant bile leak, no unplanned transfer to the ICU, no 30-day mortality, no 30-day readmission, and no R1 margins for cancer cases. Among 686 RH patients (371 live donor and 315 cancer cases), a TO was achieved in 92.2% of RH donors and 53.7% of RH cancer cases. Live donor patients tended to be younger, healthier, and thinner. Among donors, increased intraoperative blood loss, and in cancer cases, male sex, tumor size, and increased intraoperative blood loss were associated with TO failure. A TO can be achieved in over 90% of patients undergoing living donor RH and in approximately half of RH cancer cases. These metrics represent a new benchmark for "real-world" TO after open RH.


IL1RAP expression and the enrichment of IL-33 activation signatures in severe neutrophilic asthma.
Interleukin (IL)-33 is an upstream regulator of type 2 (T2) eosinophilic inflammation and has been proposed as a key driver of some asthma phenotypes. To derive gene signatures from in vitro studies of IL-33-stimulated cells and use these to determine IL-33-associated enrichment patterns in asthma. Signatures downstream of IL-33 stimulation were derived from our in vitro study of human mast cells and from public datasets of in vitro stimulated human basophils, type 2 innate lymphoid cells (ILC2), regulatory T cells (Treg) and endothelial cells. Gene Set Variation Analysis (GSVA) was used to probe U-BIOPRED and ADEPT sputum transcriptomics to determine enrichment scores (ES) for each signature according to asthma severity, sputum granulocyte status and previously defined molecular phenotypes. IL-33-activated gene signatures were cell-specific with little gene overlap. Individual signatures, however, were associated with similar signalling pathways (TNF, NF-κB, IL-17 and JAK/STAT signalling) and immune cell differentiation pathways (Th17, Th1 and Th2 differentiation). ES for IL-33-activated gene signatures were significantly enriched in asthmatic sputum, particularly in patients with neutrophilic and mixed granulocytic phenotypes. IL-33 mRNA expression was not elevated in asthma whereas the expression of mRNA for IL1RL1, the IL-33 receptor, was up-regulated in the sputum of severe eosinophilic asthma. The mRNA expression for IL1RAP, the IL1RL1 co-receptor, was greatest in severe neutrophilic and mixed granulocytic asthma. IL-33-activated gene signatures are elevated in neutrophilic and mixed granulocytic asthma corresponding with IL1RAP co-receptor expression. This suggests incorporating T2-low asthma in anti-IL-33 trials.


1H and 13C NMR assignments of new methoxylated furanoflavonoids from Lonchocarpus araripensis.
Two new polymethoxylated flavonoids, 2',5',6'-trimethoxy-[2'',3'' : 3',4']furano dihydrochalcone and 2,4',4,5-tetramethoxy-[2'',3'' : 6,7]-furanodihydroaurone, were isolated from the root barks of Lonchocarpus araripensis, along with the known compounds 3,4,5,6-tetramethoxy-[2'',3'' : 7,8]-furanoflavan, 3,6-dimethoxy-1'',1''-dimethylcromene-[2'',3'' : 7,8]-flavone, 3',4'-methylenodioxy-5,6-dimethoxy-[2'',3'' : 7,8]-furanoflavone, 3,5,6-trimethoxy-[2'',3'' : 7,8]-furanoflavanone, 3,5,6-trimethoxy-[2'',3'' : 7,8]-furanoflavone, and 6alpha-hydroxy-medicarpin. The complete (1)H and (13)C NMR assignments of the new furan flavonoids were performed using 1D and 2D pulse sequences, including COSY, HSQC, and HMBC experiments, and comparison with spectral data for analog compounds from the literature, particularly for the new furanodihydroaurone because of several inconsistencies on the carbonyl chemical shifts from the literature.


Current status and practical considerations of artificial intelligence use in screening and diagnosing retinal diseases: Vision Academy retinal expert consensus.
The application of artificial intelligence (AI) technologies in screening and diagnosing retinal diseases may play an important role in telemedicine and has potential to shape modern healthcare ecosystems, including within ophthalmology. In this article, we examine the latest publications relevant to AI in retinal disease and discuss the currently available algorithms. We summarize four key requirements underlining the successful application of AI algorithms in real-world practice: processing massive data; practicability of an AI model in ophthalmology; policy compliance and the regulatory environment; and balancing profit and cost when developing and maintaining AI models. The Vision Academy recognizes the advantages and disadvantages of AI-based technologies and gives insightful recommendations for future directions.


Effect of antineoplastic agents on the expression of human telomerase reverse transcriptase beta plus transcript in MCF-7 cells.
To evaluate the effect of antineoplastic agents on the expression of human telomerase reverse transcriptase (hTERT) splice variants in MCF-7 cells. We have developed a luminometric hybridization assay for hTERT beta plus transcript. MCF-7 cells were isolated before and after treatment with antineoplastic agents. A combination of nested RT-PCR and the developed luminometric hybridization assay was used for the specific detection of hTERT beta plus transcript in treated and untreated MCF-7 cells. Amplification of all hTERT splicing variants by nested PCR in the same samples was also performed. MCF-7 cells treated with taxol and etoposide were found positive for all hTERT splicing variants, while the expression of hTERT beta plus transcript did not differ significantly before and after exposure. MCF-7 cells treated with doxorubicin and 5-fluorouracil did not express any of hTERT splicing variants. In the presence of cisplatin, three splicing variants of hTERT were detected. The developed hybridization assay is highly sensitive and specific for the detection of hTERT beta plus transcript in clinical samples.


Epidemiology of bovine cysticercosis and associated economic losses in the state of Rio Grande do Sul, Brazil.
Bovine cysticercosis (BCC) is the most frequently detected zoonosis in Brazilian slaughterhouses and is considered a problem for public health and beef production chain, requiring epidemiological studies focusing on evaluating its prevalence, spatial distribution, and economic losses in order to improve and adopt specific strategies for BCC control. Thus, this study focused to establish BCC prevalence and spatial distribution in the state of Rio Grande do Sul, Brazil, and estimate the economic losses for cattle farmers suppliers of one exporter slaughterhouse. A set of 70,591 bovine carcasses were postmortem inspected from 2019 to 2020, which came from 134 municipalities located in eight distinct regions in the state of Rio Grande do Sul. The prevalence found was 3.44% (C.I. 95% 3.30-3.57%), and animals infected with unviable cysticerci were more frequently detected (70.56%) than those carrying viable ones (29.44%). The most frequent destination of carcasses and viscera was non-export (65.48%), followed by freezing/salting (25.41%), heat treatment (8.74%), and rendering (0.37%), resulting in a total economic burden of at least US$ 167,868.53 for cattle farmers. Some regions had higher risk for BCC occurrence, such as Porto Alegre, Caxias do Sul, Santa Maria, Ijuí, and Passo Fundo (OR > 1, p < 0.05), respectively. These results highlight the need of adopting prophylactic measures, mainly in specific areas, in order to control BCC and reduce the economic losses for beef production chain.


Ulnar dimelia.
Ulnar dimelia ("mirror hand") is a rare congenital anomaly of the upper extremity characterized by duplication of the ulna, absence of the radial ray, and polydactyly. A case report is presented in which the patient had seven triphalangeal digits arranged in a radial cluster of three and an ulnar cluster of four. Emphasis is placed on the technique of one-stage thumb reconstruction with the use of the principles described by Buck-Gramcko.


Accelerated vertebral bone loss in relation to the menopause: a cross-sectional study on lumbar bone density in 286 women of 46 to 55 years of age.
Bone mineral density (BMD) of the lumbar spine was measured in 286 women (46-55 years of age) using dual photon absorptiometry. The women were classified in three categories: premenopausal, perimenopausal and postmenopausal. The postmenopausal group was subdivided according to the number of years since the last uterine bleeding. With multiple linear regression analysis of lumbar BMD on age and menopausal status, an acceleration of bone loss was observed during the perimenopausal period and the following first two postmenopausal years. No significant bone loss was detected in relation to age or during the later postmenopausal years. Applying both an additive and a multiplicative model of bone loss, the mean perimenopausal bone loss was 0.061 gram-equivalents hydroxyapatite (geqHA)/cm2 and 6.4%, respectively. In the first 2 postmenopausal years the mean bone loss was 0.044 geqHA/cm2 and 5.1% per year. These results suggest a substantial menopause related acceleration of lumbar bone loss in a relatively short time span with its onset in the perimenopausal period.


Measuring nestedness: A comparative study of the performance of different metrics.
Nestedness is a property of interaction networks widely observed in natural mutualistic communities, among other systems. A perfectly nested network is characterized by the peculiarity that the interactions of any node form a subset of the interactions of all nodes with higher degree. Despite a widespread interest on this pattern, no general consensus exists on how to measure it. Instead, several nestedness metrics, based on different but not necessarily independent properties of the networks, coexist in the literature, blurring the comparison between ecosystems. In this work, we present a detailed critical study of the behavior of six nestedness metrics and the variants of two of them. In order to evaluate their performance, we compare the obtained values of the nestedness of a large set of real networks among them and against a maximum-entropy and maximum-likelihood null model. We also analyze the dependencies of each metrics on different network parameters, as size, fill, and eccentricity. Our results point out, first, that the metrics do not rank networks universally in terms of their degree of nestedness. Furthermore, several metrics show significant dependencies on the network properties considered. The study of these dependencies allows us to understand some of the observed systematic shifts against the null model. Altogether, this paper intends to provide readers with a critical guide on how to measure nestedness patterns, by explaining the functioning of several metrics and disclosing their qualities and flaws. Besides, we also aim to extend the application of null models based on maximum entropy to the scarcely explored area of ecological networks. Finally, we provide a fully documented repository that allows constructing the null model and calculating the studied nestedness indexes. In addition, it provides the probability matrices to build the null model for a large dataset of more than 200 bipartite networks.


Fast Science and Sluggish Policy: The Herculean Task of Regulating Biodiscovery.
New rules for access and benefit sharing (ABS) of genetic resources and associated traditional knowledge have been established by the Nagoya Protocol but have not kept up with rapid scientific and technological advances in biodiscovery. This suggests the need for innovative, transdisciplinary approaches to regulate ABS and emerging technologies.


Activation of pre-supplementary motor area (SMA) and SMA proper during unimanual and bimanual complex sequences: an analysis using functional magnetic resonance imaging.
Several functional imaging studies have shown that the extent of activation and percentage change in cerebral blood flow in the supplementary motor area (SMA) during a bimanual mirror performance of a simple repetitive movement are almost identical to those during a unimanual movement. The aim of this study was to investigate whether this finding was also applicable to a more complex movement. Eight right-handed, healthy volunteers performed unimanually (with their right and left hands) and bimanually (in a mirror fashion) thumb-finger opposition in a nonconsecutive order (index-middle-index-ring-index-little-index-middle ... fingers). The SMA proper was more activated during the bimanual movement than the unimanual movement with either hand. This is in accordance with the hypothesis that bimanual movement, even in a mirror fashion, is more difficult than unimanual movement when the task is complex but not when the task is simple. Pre-SMA was inconsistently activated. The results suggest that the SMA proper plays an active role in executive processing during bimanual mirror performance of complex movements.


Protozoan and helminth infections in pregnancy. Short-term and long-term implications of transmission of infection from mother to foetus.
This review of protozoan and helminth infections in pregnancy focuses on the impact on the immune response in the newborn infant to maternal infection. Studies of protozoan and helminth infections in pregnant women and in their offspring have shown that children exposed to antigens or microorganisms during pregnancy often have a reduced immune response to these infections. The most common finding is a reduced IFN gamma response to specific antigens regardless of specific infection studied. In some studies the impaired immune response disappeared before the age of one year, while in other studies the impaired immune response was present as much as two decades after birth. Data from chronic viral infections like Rubella, cytomegalovirus and hepatitis B also show that congenital or perinatal infections may result in a life-long inability to control the infections. Studies of both helminth and protozoan infections show that children exposed to antigens during gestation have a microorganism-specific impaired immune response which is characterized by reduced IFN-gamma and stimulation of responses to specific antigens.


The hemizona assay (HZA): a predictor of human sperm fertilizing potential in in vitro fertilization (IVF) treatment.
The hemizona assay (HZA) was developed to assess human sperm fertilizing potential. This blinded study investigated the relationship between sperm binding to the hemizona and in vitro fertilization (IVF) success (36 patients). Nonliving human oocytes were recovered from excised ovaries and stored. Each zona pellucida was cut into equal hemispheres by micromanipulation. For the HZA, one droplet exposed a hemizona to abnormal spermatozoa, while the control droplet contained the matching hemizona and spermatozoa from normal semen. After 4 hr, the number of tightly bound spermatozoa was counted. Binding to the hemizona was significantly higher for those having IVF success (mean of 36.1 +/- 7, versus 10.4 +/- 4 from the failure group; P less than 0.05). Fewer sperm from the failure group had a strictly normal morphology (3.2 versus 12.7%; P less than 0.05, Kruger method). Tight zona binding was significantly correlated with the percentage motile sperm, percentage normal morphology, and seminal sperm concentration. These results enhanced our confidence that the HZA is diagnostic for identification of patients at high risk of failing to achieve fertilization in vitro.


Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer.
Prompt detection of colorectal cancer (CRC) among individuals younger than age 50 years (early-onset CRC) is a clinical priority because of its alarming rise. We conducted a matched case-control study of 5075 incident early-onset CRC among US commercial insurance beneficiaries (113 million adults aged 18-64 years) with 2 or more years of continuous enrollment (2006-2015) to identify red-flag signs and symptoms between 3 months to 2 years before the index date among 17 prespecified signs and symptoms. We assessed diagnostic intervals according to the presence of these signs and symptoms before and within 3 months of diagnosis. Between 3 months and 2 years before the index date, 4 red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) were associated with an increased risk of early-onset CRC, with odds ratios (ORs) ranging from 1.34 to 5.13. Having 1, 2, or at least 3 of these signs and symptoms were associated with a 1.94-fold (95% confidence interval [CI] = 1.76 to 2.14), 3.59-fold (95% CI = 2.89 to 4.44), and 6.52-fold (95% CI = 3.78 to 11.23) risk (Ptrend < .001), respectively, with stronger associations for younger ages (Pinteraction < .001) and rectal cancer (Pheterogenity = .012). The number of different signs and symptoms was predictive of early-onset CRC beginning 18 months before diagnosis. Approximately 19.3% of patients had their first sign or symptom occur between 3 months and 2 years before diagnosis (median diagnostic interval = 8.7 months), and approximately 49.3% had the first sign or symptom within 3 months of diagnosis (median diagnostic interval = 0.53 month). Early recognition of red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia) may improve early detection and timely diagnosis of early-onset CRC.


Oxidation and degradation of native wheat starch by acidic bromate in water at room temperature.
Native wheat starch was oxidized by benign acidic bromate in water at room temperature. HPLC-ELSD study indicated that starch degraded in the course of oxidation but it still had a polymeric structure characterized by (1)H, (13)C, HSQC and HMBC NMR measurements. Products were generally water-soluble fragments but the use of a short reaction time and dilute reaction mixture yielded water-insoluble products. Titration of the products showed, that the increase of the starch content and reaction time increased the content of carbonyl and carboxyl groups in the range of 0.5-2.5% and 1.7-17.2%, respectively, in the product fragments. A mechanism for the oxidation reaction was proposed.


Cut umbilical cord milking (C-UCM) as a mode of placental transfusion in non-vigorous preterm neonates: a randomized controlled trial.
Routine practice of delayed cord clamping (DCC) is the standard of care in vigorous neonates. However there is no consensus on the recommended approach to placental transfusion in non-vigorous neonates. In this trial, we tried to examine the effect of cut umbilical cord milking (C-UCM) as compared to early cord clamping (ECC) on hematological and clinical hemodynamic parameters in non-vigorous preterm neonates of 30-35 weeks gestation. The primary outcome assessed was venous hematocrit (Hct) at 48 (± 4) hours of postnatal age. The important secondary outcomes assessed were serum ferritin at 6 weeks of age, mean blood pressure in the initial transitional phase along with important neonatal morbidities and potential complications. In this single centre randomized controlled trial, 134 non vigorous neonates of 30-35 weeks gestation were allocated in a 1:1 ratio to either C-UCM (n = 67) or ECC (n = 67). For statistical analysis, unpaired Student t and Chi square or Fisher's exact test were used. The mean Hct at 48 h was higher in the C-UCM group as compared to the control group, 50.24(4.200) vs 46.16(2.957), p < .0001. Also significantly higher was the mean Hct at 12 h, 6 weeks and mean serum ferritin at 6 weeks of age in the milked group (p < .0001). Mean blood pressure at 1 h and 6 h was also significantly higher in the milked arm. Need for transfusion and inotropes was less in the milked group but not statistically significant. No significant difference in potential complications was observed between the groups. Conclusion: C-UCM stabilizes initial blood pressure and results in higher hematocrit and improved iron stores. It can be an alternative to DCC in non-vigorous preterm neonates of 30-35 weeks' gestation. Further large multicentric studies are needed to fully establish its efficacy and safety. Trial registration: CTRI/2021/12/038606; registration date December 14, 2021. What is Known: • DCC is the routinely recommended method of placental transfusion for vigorous neonates but no consensus exist for neonates requiring resuscitation at birth. • C-UCM is easier to perform in non-vigorous neonates but there is paucity of studies in the preterm population. What is New: • C-UCM is effective as well as safe in non-vigorous preterm neonates of 30-35 weeks gestational age. • C-UCM holds promise as an alternative to DCC, especially in resource limited settings and in situations where the later is not feasible.


Dietary Intake and Nutritional Status among Refugees in Host Countries: A Systematic Review.
Refugees remain vulnerable to acute food insecurity, malnutrition, and critically inadequate food and nutrient intake after migration, regardless of the economic level of the host country. We conducted this systematic review to summarize and evaluate the dietary intake and nutritional status among refugees resettled in non-camp settings worldwide. We searched PubMed and Web of Science databases to review relevant studies published between 2009 and 2020 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We also conducted an additional manual search through PubMed and Google Scholar. Studies that evaluated both dietary intake and nutritional status of refugees in host countries were included. A total of 15 articles from 10 countries were included and assessed for study quality and outcomes. Poor dietary diversity and insufficient intake of specific food groups were reported. In addition to these dietary patterns, a high prevalence of stunting, underweight, and anemia was reported, particularly among children. A double burden of malnutrition was also observed across and within studies. Post-resettlement dietary intake and nutritional status of refugees are both influenced by factors at the pre- and post-resettlement stages as refugees transition to their host countries. Those factors, including pre-resettlement experiences, host country resources, socioeconomic status, acculturation, and food security, were summarized and presented in a conceptual model. There is a need for comprehensive dietary and health screening as well as culturally appropriate and sustainable nutrition education resources and interventions for refugees to improve their diet and nutrition. Longitudinal studies and novel methodological approaches are also suggested to measure changes in refugees' food intake and nutritional status as well as to further investigate factors associated with these 2 components.


Associations of active and passive smartphone use with measures of youth mental health during the COVID-19 pandemic.
Smartphone use provides a significant amount of screen-time for youth, and there have been growing concerns regarding its impact on their mental health. While time spent in a passive manner on the device is frequently considered deleterious, more active engagement with the phone might be protective for mental health. Recent developments in mobile sensing technology provide a unique opportunity to examine behaviour in a naturalistic manner. The present study sought to investigate, in a sample of 451 individuals (mean age 20.97 years old, 83% female), whether the amount of time spent on the device, an indicator of passive smartphone use, would be associated with worse mental health in youth and whether an active form of smartphone use, namely frequent checking of the device, would be associated with better outcomes. The findings highlight that overall time spent on the smartphone was associated with more pronounced internalizing and externalizing symptoms in youth, while the number of unlocks was associated with fewer internalizing symptoms. For externalizing symptoms, there was also a significant interaction between the two types of smartphone use observed. Using objective measures, our results suggest interventions targeting passive smartphone use may contribute to improving the mental health of youth.


Detection and Management of Obstructive Azoospermia.
Obstructive azoospermia represents a treatable form of male factor infertility. With greater demand for assisted reproductive technologies the general urologist may be tasked with initiating the infertility evaluation and providing counsel for treatment options. In this review we discuss appropriate laboratory, radiographic and genetic testing for the patient with obstructive azoospermia. We also outline surgical treatment options. The Medline® database was searched for relevant studies of the evaluation and treatment of men with obstructive azoospermia. Key words included obstructive azoospermia, vasovasostomy, vasoepididymostomy, testicular sperm extraction, sperm aspiration and sperm retrieval. Most published reports were based on small cohorts followed at single institutions. There were sufficient data to characterize the current state of the art and review the standard of practice. The initial evaluation of azoospermia is primarily based on differentiating obstructive from nonobstructive etiologies with a substantial reliance on history, physical examination and screening laboratory studies. Various treatment options exist for obstructive azoospermia, including reproductive tract reconstruction (vasovasostomy or vasoepididymostomy) or numerous surgical sperm extraction approaches.


[A rare cause of postoperative acute respiratory insufficiency: diaphragmatic hernia].
A case of postoperative failure after total hip replacement is described. A gastric tube was passed and the stomach was seen to be within the right hemithorax on the chest X-ray. Aspiration of gastric gas and juice relieved the respiratory symptoms.


Estimating the Cost per Clinical Outcome of Second-Line Liso-Cel Versus Autologous Stem Cell Transplantation in Patients with Transplantation-Intended Relapsed/Refractory Large B Cell Lymphoma.
It is important to consider the total cost of care (TCOC) associated with a therapy and clinical benefit for relapsed or refractory (R/R) large B cell lymphoma (LBCL). We estimated the 1-year TCOC and cost per clinical outcome for patients with R/R LBCL treated with second-line lisocabtagene maraleucel (liso-cel) versus autologous stem cell transplantation (ASCT) using data from the TRANSFORM study (ClinicalTrials.gov NCT03575351). A cost per clinical outcome analysis using a Monte Carlo simulation approach was conducted. Cost inputs were generated from a retrospective microcosting analysis of healthcare resource utilization (HCRU). Patient-level data from an interim analysis (March 2021) were used to derive HCRU and clinical inputs. Clinical inputs included median event-free survival (EFS), median progression-free survival (PFS), objective response rate, and complete response (CR) rate. In the intention-to-treat analysis, the mean (standard deviation) TCOC per patient was $550,864 ($173,087) for liso-cel and $413,200 ($290,802) for ASCT. The cost per clinical outcome model estimated a mean cost for liso-cel versus ASCT per EFS month of $57,295 versus $186,369, per PFS month of $40,949 versus $78,797, per overall responder of $653,965 versus $881,804, and per complete responder of $828,045 versus $1,063,822. This economic model shows reductions in mean estimated TCOC per EFS month, PFS month, overall responder, and complete responder with liso-cel versus ASCT owing to the superior efficacy of liso-cel. Although liso-cel-treated patients incurred greater upfront costs, fewer required subsequent therapy, and they accumulated less downstream costs. These results underscore the importance of considering the durability of response and clinical benefit when assessing total costs.


New lead discovery of insect growth regulators based on the scaffold hopping strategy.
Insect growth regulators (IGRs), which can interrupt or inhibit pest life cycles, are low-toxicity pesticides widely used in integrated pest management (IPM). Ecdysone analogues and chitinase inhibitors are familiar IGRs that have attracted considerable attention because of their unique modes of action and low toxicity to non-target organisms. To find new and highly effective candidate IGRs with novel mechanisms, D-08 (N-(4-(tert-butyl)phenyl)-2-phenyl-2,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-5-carboxamide) was chosen as a lead compound, and a series of novel heptacyclic pyrazolamide derivatives were designed and synthesized using the scaffold hopping strategy. The bioassay showed that III-27 (N-(2-methylphenethyl)-1-phenyl-1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-5-carboxamide) had excellent activity against Plutella xylostella. Protein verification and molecular docking indicated that III-27 could act on both the ecdysone receptor (EcR) and Ostrinia furnacalis chitinase (Of ChtI) and is a promising new lead IGRs. The interaction mechanism of III-27 with EcR and Of ChtI was then studied by molecular docking. These results provide important guidance for the study of new dual-target IGRs.


Clinical impact of endoscopic submucosal dissection for gastric neuroendocrine tumors: a retrospective study from mainland China.
As a minimally invasive technique, endoscopic resection may benefit patients diagnosed with early stage gastrointestinal neuroendocrine tumors (NETs). However, no studies have yet been published in which endoscopic submucosal dissection (ESD) has been applied for gastric NETs. For the first time a research group in China applied ESD to remove gastric NETs, and indicated that ESD should be considered for treatment of eligible gastric NETs because the technique shows a high histologically complete resection rate, provides accurate histopathological evaluation, has a low complication rate, and can be performed within a reasonable timeframe.


An epithelial-derived factor inhibits contraction in canine perfused bronchial segments.
We have previously reported, using a novel preparation of canine airway segments, that the sensitivity of acetylcholine was greater when applied to the adventitial (outside) surface than the epithelial (inside) surface. The present study investigated if this "barrier-effect" was partly the result of pharmacological modulation by the epithelium. As previously demonstrated, canine airway segments were less sensitive to inside than outside application of acetylcholine (pD(2) 3.0+/-0.4 and 4.5+/-0.4, respectively, P<0.001, n=5). The addition of donor bronchi significantly decreased the sensitivity of the airway segment to outside application of acetylcholine (pD(2) 4.3+/-0.2 and 3.6+/-0.2, respectively, P<0.002, n=4). Indomethacin (2.5 microM) treatment of both the donor bronchi and the airway segment and removal of donor epithelium abolished the rightward shift in the acetylcholine-response curves. In addition, inhibition of cyclooxygenase within the airway segments themselves, but not the donor bronchi, also inhibited the rightward shift in the curves. These results indicate that the donor epithelium is capable of pharmacologically modulating responses of the airway segment to outside applied acetylcholine by producing an epithelial-derived factor, which in turn causes the release of a downstream cyclooxygenase product from within the airway segment.


Enzyme immobilization: an overview on techniques and support materials.
The current demands of the world's biotechnological industries are enhancement in enzyme productivity and development of novel techniques for increasing their shelf life. These requirements are inevitable to facilitate large-scale and economic formulation. Enzyme immobilization provides an excellent base for increasing availability of enzyme to the substrate with greater turnover over a considerable period of time. Several natural and synthetic supports have been assessed for their efficiency for enzyme immobilization. Nowadays, immobilized enzymes are preferred over their free counterpart due to their prolonged availability that curtails redundant downstream and purification processes. Future investigations should endeavor at adopting logistic and sensible entrapment techniques along with innovatively modified supports to improve the state of enzyme immobilization and provide new perspectives to the industrial sector.


Modification of enzymatic activity and difference spectra of cytochrome P-450 from various sources by cholesterol side chain cleavage inhibitors.
Several groups of compounds were tested for their ability to inhibit cholesterol side chain cleavage and induce spectral change in cytochrome P-450 from bovine corpus luteum, bovine adrenal cortex, and human placental mitochondria. The substances tested include: steroids, pyridines, glutarimides, anilines and imidazoles. Good correlation was found between spectral change and enzymatic inhibition, especially in the corpus luteum which has only a single P-450-linked steroid hydroxylase. The cholesterol side chain cleavage enzyme systems from each of the three sources appear to have similar affinities for the inhibitors, which adds further support to the concept that these cytochrome P-450s are functionally identical.


Draft Genome Sequence of Tokyovirus, a Member of the Family Marseilleviridae Isolated from the Arakawa River of Tokyo, Japan.
Members of the Marseilleviridae family are large DNA viruses with icosahedral particles that infect Acanthamoeba cells. This report presents a new Marseilleviridae family member discovered in a water/soil sample from a river in Tokyo, named Tokyovirus, with genome size of 370 to 380 kb.


Abnormalities of leukotaxis in atopic dermatitis.
Leukocyte chemotaxis studies were performed in 14 patients with atopic dermatitis. Monocyte chemotactic responsiveness (MCR), polymorphonuclear leukocyte (PMN) chemotactic responsiveness (PCR), and patient serum inhibition of normal monocyte chemotaxis were evaluated. The most common defect noted was depressed MCR. This was found in 8 of the 14 patients and was associated with a chemotactic inhibitor in the serum of 5 of 6 of the 8 with depressed MCR whose sera were so tested. Depressed PCR was found in 3 of 10 patients studied. Ten of the 14 patients had depressed chemotaxis of at least one cell type. Depressed chemotaxis was not related to the presence of infection, to the serum IgE level, or to the severity of the eczema, and it could not be produced in vitro by incubating normal cells with histamine or IgE myeloma. These studies demonstrate a high frequency of leukocyte chemotactic abnormalities in patients with severe atopic dermatitis. Elucidation of the clinical significance of the leukotactic abnormalities observed and determination of whether they are basic or secondary to the disease process must await further study.


Case series on high grade appendiceal cancer with peritoneal and liver carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).
Pseudomyxoma Peritonei (PMP) is a mucin producing cancer with appendix as primary site. Cytoreductive Surgery (CRS) combined with hyper-thermic intraperitoneal chemotherapy (HIPEC) is an established form of therapy known to prolong survival in patients with PMP and peritoneal carcinomatosis. Methods/patients In our case series, we present five cases of PMP with synchronous liver and peritoneal metastasis treated with CRS and HIPEC. It is a very rare condition which needs more research to be able to comment on overall survival. However, in our study, we found lower age, female gender and complete cytoreduction in surgery to be favourable predictors for improved morbidity. In our experience, CRS/HIPEC seem to be feasible for patients with PMP with synchronous liver and peritoneal metastasis.


Ultrafast Long-Range Charge Separation in Organic Photovoltaics: Promotion by Off-Diagonal Vibronic Couplings and Entropy Increase.
The exciton dissociation in a model donor/acceptor heterojunction with electron-phonon couplings is simulated by a full quantum dynamical method, in which ultrafast long-range charge separation is observed. Such a novel scenario does not undergo short-range interfacial (pinned) charge transfer states, but can be mainly ascribed to the quantum resonance between local Frenkel excited states and a broad array of long-range charge transfer (LRCT) states assisted by the moderate off-diagonal vibronic couplings. The entropy-increasing effect associated with the very dense density of states for LRCT states is also found to be beneficial for lowering the free energy barrier for charge generation in organic solar cells.


General features in the stoichiometry and stability of ionophore A23187-cation complexes in homogeneous solution.
Existing literature describing the stoichiometry and stability of complexes between A23187 and divalent cations in solution has been extended to include additional transition series cations, the heavy-metal cations Cd2+ and Pb2+, plus seven lanthanide series trivalent cations. Stability constants of 1:1 complexes between the ionophore and the divalent cations vary by 6.2 orders of magnitude between Cu2+ and Ba2+ which are the strongest and weakest complexes, respectively. Considering alkaline-earth and first-series transition cations together, the pattern of stability constants obeys the extended Irving-Williams series as is seen with many nonionophorous liganding agents. Cd2+ and Pb2+ are bound with an affinity similar to those of Mn2+ and Zn2+, whereas the lanthanides are bound with little selectivity and slightly higher stability. Titration of the ionophore in the 10(-5) M concentration range with di- and trivalent cations gives rise first to complexes of stoichiometry MA2 and subsequently to MA as the metal concentration is increased. The second stepwise stability constants for formation of the MA2 species exceeds the first constant by approximately 10-fold. With lanthanides, heavy metals, and transition-metal cations, OH-, at near physiological concentrations, competes significantly with free ionophore for binding to the 1:1 complexes. This competition is not apparent when Ca2+ or Mg2+ are the central cations. Possible implications of the 1:1 complex selectivity pattern, the ionophore-hydroxide competitive binding equilibria, and potential ternary complexes involving 1:1 ionophore:cation complexes and other anions present in biological systems are discussed with respect to the ionophore's transport selectivity and biological actions.


Hydration shells of molecules in molecular association: A mechanism for biomolecular recognition.
It has become clear that water should not be treated as an inert environment, but rather as an integral and active component of molecules. Here, we consider molecules and their hydration shells together as single entities. We show that: (1) the rate of association of molecules should be determined by the energetic barriers arising from interactions between their hydration shells; (2) replacing non-polar atoms of molecular surfaces with polar atoms increases these barriers; (3) reduction of the hydration shells during molecular association is the driving force for association not only of non-polar, but of polar molecules as well; (4) in most cases the dehydration of polar atoms during molecular association thermodynamically counteracts association; (5) on balance the thermodynamic stability of associated complexes is basically determined by the action of these two opposing factors: reduction of the hydration shells and dehydration of polar atoms; (6) molecular crowding reduces the energetic barriers counteracting association and changes the thermodynamic stability of associated complexes. These results lead to a mechanism for biomolecular recognition in the context of which the formation of unique structures is provided by rapidly forming kinetic traps with a biologically necessary lifetime but with a marginal thermodynamic stability. The mechanism gives definitive answers to questions concerning the heart of specific interactions between biomolecules, their folding and intracellular organization. Predictions are given that can be subjected to direct experimental tests.


Intracerebroventricular administration of bombesin inhibits biliary and gastric secretion in the rat.
The effect of intracerebroventricular (ICV) bombesin on bile and gastric acid secretion was examined in the rat. ICV bombesin (10 micrograms in 10 microliters) inhibited basal biliary volume by 27% and bile bicarbonate by 52% of control values, while gastric acid secretion was decreased by 75%. These results provide evidence for central mechanisms for the control of gastrointestinal function.


Diagnostic accuracy of Panbio™ rapid antigen test for SARS-CoV-2 in paediatric population.
Rapid antigen-detection tests (Ag-RDTs) are used to diagnose SARS-CoV-2 infection. Real-world studies of Ag-RDTs are necessary to evaluate their diagnostic yield in paediatric patients. Our aim was to evaluate the accuracy of the Panbio™ Rapid Antigen Test for SARS-CoV-2 in the setting of a primary health care centre (PHC), with use of the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) as gold standard. This prospective diagnostic study was conducted at PHCs in Mallorca, Spain. Patients were ≤ 18 years-old that attended sites for RT-PCR testing due to symptoms suggestive of infection (fever, headache, nasal congestion and dry cough, among others) or epidemiological exposure (close contacts). Two samples were collected: a nasal mid-turbinate sample for Ag-RDTs and a nasopharyngeal swab for RT-PCR testing. The sensitivity, specificity, and predictive values of the AgRDT were calculated using the RT-PCR results as the reference. We examined 1142 participants from 0 to 18 years (47.5% female, mean age 8.9 ± 4.8 years, median 9.0 [5.0-13.0]). There were 84 positive RT-PCR results (pre-test probability of 7.3%) and 52 positive Ag-RDT results. The sensitivity of the Ag-RDT was 59.5% (95% Confidence Interval (CI): 48.2-69.9%), the specificity was 99.8% (95%CI: 99.2-99.9%), the positive predictive value was 96.1% (95%CI: 85.6-99.4%), and the negative predictive value was 96.8% (95%CI: 95.6-97.7%). The sensitivity for individuals referred by a general practitioner (GP) or paediatrician due to symptoms was 71.4% (95%CI: 51.5-86.0%) and for asymptomatic individuals was 50.0% (95%CI: 9.1-90.8%). The specificity was greater than 98.9% overall and in all subgroups. The sensitivity was 73.0% (95%CI: 52.0-87.5%) for referred patients due to symptoms and who were tested within 5 days since symptom onset. No significant statistical differences between any groups were found. There were 34 false-negative Ag-RDT results (40.5%) and 2 false-positive Ag-RDT results (0.2%). The sensitivity of the Panbio™ Test in paediatric individuals is below the minimum of 80% recommended by the World Health Organization for Ag-RDTs. This test had better accuracy in individuals referred by a GP or paediatrician due to symptoms, rather than those who were asymptomatic or referred due to epidemiological exposure. The RT-PCR test using a nasopharyngeal swab is accurate, but a less invasive alternative that has better sensitivity than the Panbio™ Test is needed for paediatric populations.


3D micro-environment regulates NF-κβ dependent adhesion to induce monocyte differentiation.
Differentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signaling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.


Supramolecular structure organization and rheological properties modulate the performance of hyaluronic acid-loaded thermosensitive hydrogels as drug-delivery systems.
The challenges for developing new pharmaceutical formulations based on natural and synthetic polymers has led to innovation into the design of systems responsive environmental stimuli such as temperature. However, the presence of hydrophilic or hydrophobic molecules, charged groups, or metallic elements can affect their structural behavior and their biopharmaceutical performance This work aims to study and characterize the morphology and structure of polymeric formulations based on Poloxamer (PL) 407 (15 % and 30 % m/v) and its binary with PL 338 (15 % PL 407 + 15 % PL 338) and hyaluronic acid (0.5 % m/v), as drug delivery systems of local anesthetic bupivacaine (0.5 % m/v) and ropivacaine (0.5 % m/v) hydrochloride. For this, it was performed SANS analysis for determination of supramolecular organization and lattice parameters; calorimetry was done to characterize their thermodynamic parameters; rheological analysis flow curve, consistency and adhesion calculation, Maxwell model study. Also, it was performed drug release profiles and calculation of diffusion coefficients. It was identified lamellar structures in PL 407 15 % formulations, and coexistence of cubic and hexagonal phases in PL 407 30 % and binary formulations, however hyaluronic acid, bupivacaine or ropivacaine seem do not affect the type of supramolecular structure. In addition, these additives can modulate viscosity among poloxamers chains, increasing micelle-micelle interactions as it happens in presence of bupivacaine. On the other hand, addition of hyaluronic acid can promote increased structural stabilization by hydrophilic interactions between hyaluronic and micellar corona. It reflects the ability how to control the drug release, as in case of binary system that retained bupivacaine for longer time than other systems, as well it happens when hyaluronic acid is added in PL 407 15 % and PL 407 30 %.


Recovery expectations of hip resurfacing compared to total hip arthroplasty: a matched pairs study.
Expectations of higher activity levels associated with hip resurfacing arthroplasty (HRA) may be driving better outcomes in this group compared to total hip arthroplasty (THA). Previous studies evaluated patient expectations before consulting with the surgeon, although these expectations were likely unrealistic and would change after the consultation. We compared HRA and THA patient expectations after consultation with the surgeon. In a prospective registry setting, patients awaiting HRA were matched to THA patients by age, sex, and a preoperative Lower Extremity Activity Scale score (range 1-18, with 18 indicating levels of highest activity). Patients completed preoperatively a validated 18-item expectations survey. Mean overall expectation scores were first compared. Exploratory factor analysis (EFA) was then performed to determine if the grouping of individual expectations items represented meaningfully different underlying factors in the 2 groups. We matched 123 pairs. The mean ± SD expectation scores were similar (85.2 ± 15.5 for HRA and 87.3 ± 13.9 for THA; P = 0.249). The EFA showed that HRA and THA patients shared the common expectations of pain relief and improvement in daily activities (9 items) and eliminating pain medications, the need for a cane, and improving sexual activity (3 items). THA patients perceived the remaining 6 items as an overall third expectation of participation in higher-level activities. However, HRA patients perceived a fourth expectation of normal range of motion (2 items) independent of the other higher-level activities (4 items). Even after consulting with a surgeon, patients' expectations differed between HRA and THA patients regarding higher-level activities. More counseling for patients seeking hip arthroplasty is therefore needed.


Medial and lateral wall decompression for thyroid ophthalmopathy.
A two-wall decompression of the orbit, consisting of removal of the medial and lateral walls, was successful in eight patients with thyroid ophthalmopathy. The lateral wall was by removed by using the standard orbitotomy technique in addition to enlarging the space with a pneumatic burr, and the medial wall was removed through a direct medial canthal incision. Two patients had optic neuropathy, one had intermittent subluxation of the globe, and five had symptoms of exposure or increased pressure in the orbital area. In our eight patients, the two with optic neuropathy improved, the patient with subluxation of the globe became asymptomatic, and the other five had less exposure and were more comfortable. The amount of decompression ranged between 4 and 7 mm. The lacrimal sac was injured in one patient; temporary silicone intubation avoided any permanent sequela.


Emerging molecular functions and novel roles for the DEAD-box protein Dbp5/DDX19 in gene expression.
The DEAD-box protein (DBP) Dbp5, a member of the superfamily II (SFII) helicases, has multiple reported roles in gene expression. First identified as an essential regulator of mRNA export in Saccharomyces cerevisiae, the enzyme now has reported functions in non-coding RNA export, translation, transcription, and DNA metabolism. Localization of the protein to various cellular compartments (nucleoplasm, nuclear envelope, and cytoplasm) highlights the ability of Dbp5 to modulate different stages of the RNA lifecycle. While Dbp5 has been well studied for > 20 years, several critical questions remain regarding the mechanistic principles that govern Dbp5 localization, substrate selection, and functions in gene expression. This review aims to take a holistic view of the proposed functions of Dbp5 and evaluate models that accommodate current published data.


Transcatheter closure of patent ductus arteriosus in infantile form of Scimitar syndrome with a type II Amplatzer Ductal Occluder.
We report a unique case of infantile form of Scimitar syndrome with a patent ductus arteriosus and pulmonary hypertension. The PDA was closed percutaneously using the new Amplatzer Ductal Occluder device type II.


[Structural and functional organization of the cerebral cortex neurons in rats with various resistance to emotional stress following administration of delta-sleep-inducing peptide].
In Wistar rats with different resistance to emotional stress (ES), subjected to stress exposure (SE), the structural organization of neurons in layer V of sensomotor cortex was studied quantitatively in brain sections stained using Nissl's cresyl violet method. One group of animals was injected with delta sleep-inducing peptide (DSIP) 1 hr before SE. In rats of control group predisposed to ES, the amount of normochromatic and moderately hypochromatic neurons was decreased as compared to the rats resistant to ES. After SE, normochromatic neurons were not demonstrated. In rats predisposed to ES, the contents of moderately hypo- and hyperchromatic neurons was found to fall dramatically with a simultaneous increase in the number of extremely hypo- and hyperchromatic neurons, ghost cells and ischemically changed cells. After DSIP infusion before SE, ischemically damaged cells were not found in any group, while the degree of shrinkage of extremely hyperchromatic neurons was lower in rats predisposed to ES as compared to rats resistant to ES. It is suggested that brain hypoxia plays an important role in cortex disorganization during ES, whereas DSIP, possesses both antistress and antihypoxic effects.


Effect of autogenous bone grafts on healing following Le Fort I maxillary osteotomies.
The healing of Le Fort I maxillary osteotomies was studied histologically in 12 adult rhesus monkeys to determine the effect of split autogenous rib grafts overlaying the osteotomy cuts on the lateral maxillary walls. The maxilla was advanced 8 mm in each animal, and examined at varying intervals up to 24 weeks after surgery. The results indicated that there were no obvious differences between the monkeys with and without the rib grafts. Both groups healed with good osseous union. It is concluded that autogenous rib grafts did not enhance bony healing.


Fatal Acute Intracranial Subdural Hematoma After Spinal Anesthesia for Cesarean Delivery: Case Report and Review of the Literature.
The authors report on the autopsy case of a 40-year-old primigravida without either coagulation disorders or anticoagulant/antiplatelet therapy, who developed a fatal intracranial subdural hematoma after spinal anesthesia (SA) for elective cesarean delivery for tocophobia.Intracranial subdural hematoma is the most dreaded complication of SA and is often misdiagnosed with postdural puncture headache.In this article, the authors discuss pathophysiological mechanisms and risk factors for the development of an intracranial subdural hematoma after SA and review the pertinent literature.


Movement for multiple sclerosis: a multi-site partnership for practice and research.
While dance programs for people with Parkinson's disease (PD) have been developed globally over the past two decades, dance programs for people with multiple sclerosis (MS) are just emerging. This article introduces three dance for MS programs and a multi-site partnership that was developed to evaluate and advance a model for dance for MS programs. The program partners convened over 2 days to share program models, consider current and planned program evaluations, and identify unique challenges and promising practices for delivering safe and effective dance for MS programs. This paper presents the findings of this convening and recommendations for dance for MS programs.Background:While dance programs for people with Parkinson's disease (PD) have been developed globally over the past two decades, dance programs for people with multiple sclerosis (MS) are just emerging. This article introduces three dance for MS programs and a multi-site partnership that was developed to evaluate and advance a model for dance for MS programs.Methods: The program partners convened over 2 days to share program models, consider current and planned program evaluations, and identify unique challenges and promising practices for delivering safe and effective dance for MS programs.Results:A set of promising practices for dance for MS programs, including recommendations for partnership, dance and movement approaches, and environmental, physical and psychosocial considerations, was developed by the program partners.Conclusions: These programs suggest that dance may be a useful modality for people with MS. Recommendations are offered to guide safe and evidence-based dance for MS practices.


Interrupted processing of paired somatosensory stimuli in short interstimulus intervals: role of thalamo-cortical oscillations.
Discrimination of consecutive sensory stimuli is imperative for proper sensory perception and behavioral response. We aimed to investigate the emergence of paired somatosensory responses in relation to the interstimulus interval (ISI) change. Paired stimulus with 35 ms, 50 ms, 80 ms, 140 ms, and 500 ms ISI was applied to the median nerve and evoked responses were recorded from the primary somatosensory cortex in rats. Early and late components of both responses were analyzed in different frequency bands. The amplitudes were comparable for the 1st responses (S1), while the amplitude of the 2nd responses (S2), and S2/S1 sensory gating ratio were significantly lower at 35 and 50 ms ISI values. S2/S1 ratio was close to 1 at 500 ms ISI. The duration and latency of the 2nd response was also different at 35 ms ISI. In the 2nd responses, area of early high-frequency oscillations (150-400 Hz) was significantly lower at 35 ms ISI values. The shaping of 2nd somatosensory response is dependent on ISIs. Early high-frequency oscillations changes without accompanying late high-frequency oscillations alterations, may indicate that reduced thalamo-cortical drive to the cortex take a part in determining the 2nd response at short ISI. Further research is required by using neuropsychiatric disorder models where somatosensory perception is impaired.


Teaching internal medicine residents to care for reproductive-age and pregnant women: an effective Web-based curriculum.
We sought to determine whether a Web-based curriculum could improve internal medicine residents' perceived preparedness and knowledge in the areas of preconception care, infertility evaluation, and management of medical conditions during pregnancy. Training in these areas has been previously identified as inadequate. Three Web-based modules were developed to teach these topics. Seventy residents at one institution were invited to complete the modules and to participate in the curriculum's evaluation over 6 months. Paper questionnaires assessed preparedness and comfort level among all participants. Web-based surveys that assessed pre/postknowledge and satisfaction among module completers accompanied each module. Ninety-seven percent completed paper questionnaires, and 59% completed 1 or more modules. At the end of the study period, module completers felt significantly more prepared than noncompleters, and improvement in comfort level was strongly associated with the number of modules completed. Knowledge improved significantly with module completion and curricular satisfaction was high. A Web-based approach to teaching these topics to internal medicine residents increased knowledge and perceived preparedness and was well received.


Neuromuscular fatigue during dynamic maximal strength and hypertrophic resistance loadings.
The purpose of this study was to compare the acute neuromuscular fatigue during dynamic maximal strength and hypertrophic loadings, known to cause different adaptations underlying strength gain during training. Thirteen healthy, untrained males performed two leg press loadings, one week apart, consisting of 15 sets of 1 repetition maximum (MAX) and 5 sets of 10 repetition maximums (HYP). Concentric load and muscle activity, electromyography (EMG) amplitude and median frequency, was assessed throughout each set. Additionally, maximal bilateral isometric force and muscle activity was assessed pre-, mid-, and up to 30 min post-loading. Concentric load during MAX was decreased after set 10 (P<0.05), while the load was maintained throughout HYP. Both loadings caused large reductions in maximal isometric force (MAX=-30±6.4% vs. HYP=-48±9.7%, P<0.001). The decreased concentric and isometric strength during MAX loading was accompanied by reduced EMG amplitude (P<0.05). Conversely, hypertrophic loading caused decreased median frequency only during isometric contractions (P<0.01). During concentric contractions, EMG amplitude increased and median frequency decreased in HYP (P<0.01). Our results indicate reduced neural drive during MAX loading and more complex changes in muscle activity during HYP loading.


Interaction between des-Tyr1-gamma-endorphin and HLA class I molecules: serological detection of an HLA-A2 subtype.
Preincubation of lymphocytes with des-Tyr1-gamma-endorphin (DT gamma E) inhibits the reaction between some HLA alloantisera and their corresponding antigens. One HLA-A2-specific antiserum was found which could detect a subtype of the HLA-A2 antigen on DT gamma E-treated lymphocytes from some donors. Comparison with the HLA-A2 subtypes as defined by a combination of cytotoxic T lymphocyte typing and biochemistry showed a complete correlation with the previously described HLA-A2.3 subtype.


Developmental continuity of oppositional defiant disorder subdimensions at ages 8, 10, and 13 years and their distinct psychiatric outcomes at age 16 years.
To test the developmental continuity, interrelationships, and predictive associations of the oppositional defiant disorder (ODD) subdimensions of irritable, headstrong, and hurtful. Data were collected from 6,328 mother-child pairs participating in the Avon Longitudinal Study of Parents and Children (United Kingdom). Developmental continuity for each subdimension was strong and interrelationships indicated that headstrong was associated mainly with irritable, whereas irritable did not cross associate with other ODD subdimensions; and hurtful was associated with lower levels of headstrong. With regard to associations at age 16 years, irritable at age 13 years was associated with depression, whereas headstrong at 13 was associated with delinquency and callous attitude; at age 13, hurtful failed to associate with any of the 3 age 16 outcomes. The results suggest that the ODD headstrong and irritable subdimensions are developmentally distinct, with small cross-over (i.e., headstrong to irritable), and are associated with unique outcomes. Hurtful does not appear to be associated with future maladjustment in children.


Identification of novel pyrazole acid antagonists for the EP1 receptor.
The discovery, synthesis and structure-activity relationship (SAR) of a novel series of EP1 receptor antagonists is described. Pyrazole acid 4, identified from a chemical array, had desirable physicochemical properties, an excellent in vitro microsomal inhibition and cytochrome P450 (CYP450) profile and good exposure levels in blood. This compound had an ED50 of 1.3 mg/kg in a rat pain model. A range of more potent analogues in the in vitro assay was identified using efficient array chemistry. These EP1 antagonists have potential as agents in the treatment of PGE2 mediated pain.


Effect of local restaurant smoking regulations on progression to established smoking among youths.
While smoke-free restaurant laws are intended to protect the public from secondhand smoke exposure, they may also discourage smoking among adolescents. There is no evidence from longitudinal studies to test this hypothesis. To examine the effect of local restaurant smoking regulations on progression to established smoking among adolescents. A cohort of 2623 Massachusetts youths, ages 12-17 years at baseline, was interviewed via random digit dial telephone survey in 2001-2002 and followed up two years later. A generalised estimating equations (GEE) logistic regression analysis was used and controlled for potential individual, household, and town level confounding factors. Progression to established smoking during the two year follow up period (defined as having smoked 100 or more cigarettes in one's life). Compared to youths living in towns with weak regulations, those living in towns with strong regulations (complete restaurant smoking bans) had less than half the odds of progression to established smoking (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.24 to 0.66). The association was stronger for youths in towns with strong regulations in effect for two or more years (OR 0.11, 95% CI 0.03 to 0.37), although it was still present for those in towns with strong regulations in effect for less than two years (OR 0.55, 95% CI 0.33 to 0.90). No relationship was found between living in a town with a medium restaurant smoking regulation (restriction of smoking to enclosed, separately ventilated areas) and rates of progression to established smoking. Local restaurant smoking bans may be an effective intervention to prevent youth smoking.


S14G-Humanin ameliorates Abeta25-35-induced behavioral deficits by reducing neuroinflammatory responses and apoptosis in mice.
Cerebral amyloid-beta protein (Abeta) deposition and associated neuroinflammation and apoptosis are increasingly recognized as an important component leading to cognitive impairment in Alzheimer's disease (AD). Humanin (HN) and its derivative, S14G-HN (HNG), are best known for their ability to suppress neuronal death induced by AD-related insults in vitro. Furthermore, limited in vivo studies show that HNG can ameliorate memory impairment induced by intracerebroventricular injection of anti-cholinergic drugs or Abeta25-35. However, the mechanism underlying the in vivo effect remains unclear. In this study, we sought to determine the effects of HNG on neuroinflammatory responses and apoptosis associated with behavioral deficits induced by Abeta25-35 in vivo. Our results indicate that intracerebroventricular injection of aggregated Abeta25-35 induced impairment of learning and memory, markedly elevated numbers of reactive astrocytes, activated microglia, and apoptotic cells, as well as remarkable increased levels of IL-6 and TNFalpha. Moreover, intraperitoneal HNG treatment ameliorated behavioral deficits, and reduced neuroinflammatory responses and apoptotic cells in the brain. Cumulatively, these finding demonstrate for the first time that HNG may have the potential for attenuating Abeta-induced cognitive deficits by reducing inflammatory responses and apoptosis in vivo, which may add to the novel evidence for anti-inflammatory and antiapoptosis properties of HNG in AD treatment.


Negative co-receptors on lymphocytes.
The past year has seen significant advances in our understanding of critical roles of negative immunoregulatory signals delivered through the B7-CD28 superfamily in regulating T cell activation and tolerance. Structural data on CTLA-4 have provided novel insights into the inhibitory functions of CTLA-4. Initial characterization of the PD-1-PD-1-ligand pathway has revealed that this pathway can downregulate TCR- and CD28-mediated signals. Recent studies indicate that ICOS exerts distinct effects at different phases of an immune response: ICOS can inhibit as well as stimulate T cell responses.


Functions of lysin motif (LysM)-containing protein in antibacterial responses of sea cucumbers, Apostichopus japonicus.
The lysin motif (LysM)-containing protein is one of widespread pattern-recognition receptors in prokaryotes and eukaryotes. Numerous LysM-containing gene sequences are present in gene databases; however, few have been well characterized, especially in echinoderms. In this study, the full-length cDNA of a novel LysM-containing gene was obtained from the sea cucumber Apostichopus japonicus, named AjLysM-1, using polymerase chain reaction (PCR) combined with rapid amplification of cDNA ends. We prepared and expressed recombinant AjLysM-1 protein (rAjLysM-1) and determined its pathogen-recognition ability by enzyme-linked immunosorbent and immunofluorescence assays. We also analyzed the tissue expression pattern and response to immune challenges of AjLysM-1 using quantitative real-time reverse transcription-PCR and in situ hybridization. The AjLysM-1 protein was predicted to be an intracellular non-secreted LysM-containing protein, highly homologous to the same protein in other marine echinoderms. AjLysM-1 transcripts were highest expressed in coelomocytes and were strikingly induced by challenge with representative bacterial and fungal polysaccharides. rAjLysM-1 showed weak binding to mannan, Pseudoalteromonas nigrifaciens, and Shewanella baltica, implying that AjLysM-1 might provide inadequate defense against Gram-negative bacteria and fungi. Notably, rAjLysM-1 also interacted with tyrosine protein kinase and filamin-B, indicating that it could be involved in focal adhesion in A. japonicus. These findings improve our understanding of the functions of LysM-containing proteins in marine echinoderms.


Neurodevelopment, vision and auditory outcomes at age 2 years in offspring of participants in the 'Women First' maternal preconception nutrition randomised controlled trial.
Maternal nutrition in preconception and early pregnancy influences fetal growth. Evidence for effects of prenatal maternal nutrition on early child development (ECD) in low-income and middle-income countries is limited. To examine impact of maternal nutrition supplementation initiated prior to or during pregnancy on ECD, and to examine potential association of postnatal growth with ECD domains. Secondary analysis regarding the offspring of participants of a maternal multicountry, individually randomised trial. Rural Democratic Republic of the Congo, Guatemala, India and Pakistan. 667 offspring of Women First trial participants, aged 24 months. Maternal lipid-based nutrient supplement initiated preconceptionally (arm 1, n=217), 12 weeks gestation (arm 2, n=230) or not (arm 3, n=220); intervention stopped at delivery. The INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) cognitive, language, gross motor, fine motor, positive and negative behaviour scores; visual acuity and contrast sensitivity scores and auditory evoked response potentials (ERP). Anthropometric z-scores, family care indicators (FCI) and sociodemographic variables were examined as covariates. No significant differences were detected among the intervention arms for any INTER-NDA scores across domains, vision scores or ERP potentials. After adjusting for covariates, length-for-age z-score at 24 months (LAZ24), socio-economic status, maternal education and FCI significantly predicted vision and INTER-NDA scores (R2=0.11-0.38, p<0.01). Prenatal maternal nutrition supplementation was not associated with any neurodevelopmental outcomes at age 2 years. Maternal education, family environment and LAZ24 predicted ECD. Interventions addressing multiple components of the nurturing care model may offer greatest impact on children's developmental potential. NCT01883193.


Early out-of-hospital experience with an impedance-compensating low-energy biphasic waveform automatic external defibrillator.
Impedance-compensating low-energy biphasic truncated exponential (BTE) waveforms are effective in transthoracic defibrillation of short-duration ventricular fibrillation (VF). However, the BTE waveform has not been examined in out-of-hospital cardiac arrest (OHCA) with patients in prolonged VF often associated with myocardial ischemia. The objective of this study was to evaluate the BTE waveform automatic external defibrillator (AED) in the out-of-hospital setting with long-duration VF. AEDs incorporating a 150-J BTE waveform were placed in 12 police squad cars and 4 paramedic-staffed advanced life support ambulances. AEDs were applied to arrested patients by first-arriving personnel, whether police or paramedics. Data were obtained from PC Data Cards within the AED. Defibrillation was defined as at least transient termination of VF. Ten patients, 64 +/- 14 years, were treated for VF with BTE shocks. Another 8 patients were in nonshockable rhythms and the AEDs, appropriately, did not advise a shock. Five of the 10 VF arrests were witnessed with a 911 call-to-shock time of 6.6 +/- 1.7 minutes. VF detection and defibrillation occurred in all 10 patients. Spontaneous circulation was restored in 3 of 5 witnessed arrest patients and 1 survived to discharge home. Fifty-one VF episodes were converted with 62 shocks. Presenting VF amplitude and rate were 0.43 +/- 0.22 (0.13-0.86) mV and 232 +/- 62 (122-353) beats/min, respectively, and defibrillation was achieved with the first shock in 7 of 10 patients. Including transient conversions, defibrillation occurred in 42 of 51 VF episodes (82%) with one BTE shock. Shock impedance was 85 +/- 10 (39-138) ohms. Delivered energy and peak voltage were 152 +/- 2 J and 1754 +/- 4 V, respectively. The average number of shocks per VF episode was 1.2 +/- 0.5 (1-3). More than one shock was needed in only 9 episodes; none required > 3 shocks to defibrillate. Impedance-compensating low-energy BTE waveforms terminated VF in OHCA patients with a conversion rate exceeding that of higher energy monophasic waveforms. VF was terminated in all patients, including those with high impedance.


P2X7 receptor knockout mice display less aggressive biting behaviour correlating with increased brain activation in the piriform cortex.
P2X7 receptors are implicated in the pathophysiology of psychiatric conditions such as depression and bipolar disorder. P2X7 receptors regulate the release of pro-inflammatory cytokines from microglia, and gain-of-function P2X7 mutations may contribute to the neuroinflammation found in affective disorders. However, the role of this receptor in mediating other mental health conditions and aberrant behaviours requires further examination. The current study we investigated the effects of germline genetic deletion of P2xr7 on social and marble burying behaviours in mice throughout the critical adolescent developmental period. Marble burying behaviour is thought to provide a mouse model of obsessive-compulsive disorder (OCD). We also characterised the effects of P2rx7 deletion on aggressive attack behaviour in adult mice and subsequently quantifieded microglial cell densities and c-Fos expression, a marker of neuronal activation. P2rx7 knockout mice displayed reduced OCD-related marble burying behaviour which was most pronounced in late adolescence/early adulthood. P2rx7 knockout mice also exhibited reduced aggressive attack behaviours in adulthood in the resident-intruder test. Reduced aggression in P2xr7 knockout mice did not coincide with changes to microglial cell densities, however c-Fos expression was elevated in the piriform cortex of P2rx7 knockout mice compared to wildtype mice. This study suggests that the P2X7 receptor might serve as a novel target for serenic or anti-OCD therapeutics.


Small bowel obstruction due to adhesive disease observed after uterine fibroid embolization.
After uterine fibroid embolization (UFE), the development of intra-abdominal adhesions, especially those involving the bowel, is a very rare complication. Seven months after UFE, a patient had a complete small bowel obstruction develop that was caused by an adhesive band between the posterior fibroid and cul-de-sac. She underwent an exploratory laparotomy, lysis of adhesion, and myomectomy. No bowel resection was needed. Inflammation after UFE may cause the development of intraperitoneal adhesions. We report an unanticipated case of a complete small bowel obstruction caused by an adhesion observed after UFE.


Prognostic factors of revitrectomy for complications in eyes with proliferative diabetic retinopathy: a retrospective multicentre study.
To identify prognostic factors for revitrectomy in patients who underwent vitrectomy for complications with proliferative diabetic retinopathy (PDR) in multicentre study. Consecutive 452 eyes of 452 patients with PDR undergoing 25-gauge microincision vitrectomy system (MIVS) in seven centres were retrospectivity reviewed. Preoperative ocular factors (baseline visual acuity [VA], vitreous haemorrhage [VH], tractional retinal detachment [TRD] and retinal photocoagulation), general factors (sex, age, diabetes duration, HbA1c level, hypertension, anti-coagulant medication and estimated glomerular filtration rate), surgical procedures (preoperative anti-vascular endothelial growth factor injection, internal limiting membrane peeling, combined cataract surgery, retinal break, and tamponade), postoperative complications for revitrectomy and postoperative VA at 6 months were evaluated. In the follow-up period of 6 months, revitrectomy was performed in 56 eyes (26.3%), and postoperative complications for revitrectomy were VH in 31 eyes (15%), TRD in 13 eyes (6.2%) and membrane proliferation in 12 eyes (5.2%). The mean LogMAR improvement from baseline to 6 months in revitrectomy group (0.39) was significantly worse than in single vitrectomy group (0.74). Diabetic duration, low baseline VA, less simple VH, TRD and air tamponade were statistical risk factors of revitrectomy, and logistic regression analysis identified low baseline VA and air tamponade also as prognostic factors of revitrectomy. Our results indicated that prognosis of VA was worse in PDR patients with revitrectomy and low baseline VA and air as the tamponade material were the potential prognostic factors of revitrectomy.


Videolaryngoscopy vs. flexible fibrescopy for tracheal intubation in patients with cervical spine immobilisation: a randomised controlled trial.
In patients with cervical spine immobilisation, tracheal intubation devices other than a direct laryngoscope are frequently used to facilitate tracheal intubation and avoid related complications. In this randomised controlled trial, we compared videolaryngoscopic and fibrescopic tracheal intubation in patients with a cervical collar. Tracheal intubation was performed using either a videolaryngoscope with a non-channelled Macintosh blade (n = 166) or a flexible fibrescope (n = 164) in patients having elective cervical spine surgery whose neck was immobilised with a cervical collar to simulate a difficult airway. The primary outcome was the first attempt success rate of tracheal intubation. Secondary outcomes were the overall success rate of tracheal intubation; time to tracheal intubation; use of additional airway manoeuvres; and incidence and severity of tracheal intubation-related airway complications. First attempt success rate was higher in the videolaryngoscope group than in the fibrescope group (164/166 (98.8%) vs. 149/164 (90.9%), p = 0.003). Tracheal intubation was successful within three attempts in all patients. Median (IQR [range]) time to tracheal intubation was shorter (50.0 (41.0-72.0 [25.0-170.0]) s vs. 81.0 (65.0-107.0 [24.0-178.0]) s, p < 0.001) and additional airway manoeuvres were less frequent (30/166 (18.1%) vs. 91/164 (55.5%), p < 0.001) in the videolaryngoscope group compared with the fibrescope group. The incidence and severity of intubation-related airway complications were not different between the two groups. When performing tracheal intubation in patients with a cervical collar, videolaryngoscopy with a non-channelled Macintosh blade was superior to flexible fibrescopy.


Draft Genome Sequence of the Protozoan Parasite Leishmania braziliensis Strain BA788, Isolated from a Clinical Case in Bahia State, Brazil.
The draft genome of the parasite Leishmania braziliensis strain BA788, which was isolated from a patient from Bahia state, Brazil, was sequenced using Illumina paired-end technology. The assembled genome is 33.5 Mb long and contains 7,603 genes. This genome will contribute to studies aimed at understanding the pathogenesis caused by this parasite strain.


Free radical generation and coupled thiol oxidation by lactoperoxidase/SCN-/H2O2.
The lactoperoxidase-catalyzed oxidation of glutathione (GSH) and thiocyanate (SCN-) was studied. Oxidation of SCN- was recorded by ultraviolet spectroscopy and by electron spin resonance (ESR). Consumption of GSH was measured by amperometric titration. One or two moles of GSH was oxidized per mole of H2O2 added, depending on the reaction conditions. Omission of SCN- prevented the oxidation of GSH. The oxidation of GSH required only catalytic amounts of SCN-, which was therefore recycled. Iodide (I-) could replace SCN-, while chloride or bromide were ineffective. The apparent Michaelis constant for SCN- was 17 microM. Oxidation of SCN- gave rise to two reactive intermediates, one stable and one unstable. The stable intermediate (-OSC. = N-(?)) decayed by a second-order reaction with a rate constant of 1.1 M-1 s-1. The decay of the unstable radical was very fast. The data (a) explain the short- and long-term antibacterial effects of lactoperoxidase-halide-H2O2 system, (b) point to possible deleterious effects due to glutathione depletion, (c) are of relevance for free radical diseases involving sulphur-centered free radicals, and (d) support previous observations on lipid peroxidation/halogenation in biological membranes, liposomes, and unsaturated fatty acids.


Skin cancer in patients with chronic radiation dermatitis.
The cases of 76 patients with chronic radiation dermatitis resulting from low-dose ionizing radiation for benign disease were reviewed retrospectively for risk factors leading to the development of neoplasia. The patients were studied with respect to original hair color, eye color, sun reactive skin type, benign disease treated, area treated, age at treatment, and age at development of first skin cancer. Analysis of data showed 37% of patients had sun-reactive skin type I, 27% had type II, and 36% had type III. Types IV through VI were not represented. There appeared to be an overrepresentation of types I and II. Increased melanin pigmentation may therefore be either directly or indirectly protective against the development of skin cancers in patients who have received low-dose superficial ionizing radiation for benign disease. The sun-reactive skin type of patients with chronic radiation dermatitis may be used as a predictor of skin cancer risk when the total dose of ionizing radiation is not known.


[A 19-year-old woman with palpitations and mitral regurgitation].
A young woman presented with palpitations. Holter monitoring revealed frequent premature ventricular complexes; echocardiography showed high-degree mitral regurgitation due to mitral valve prolapse. While mitral valve replacement or repair were being discussed, a different therapy was applied after further diagnostic work-up of the patient which in retrospect appears even more efficient.