Effect of logarithmic perturbations in ohmic like spectral densities in dynamics of electronic excitation using variational polaron transformation approach.
Electronic excitation energy transfer is a ubiquitous process that has generated prime research interest since its discovery. Recently developed variational polaron transformation-based second-order master equation is capable of interpolating between Förster and Redfield limits with exceptional accuracy. Forms of spectral density functions studied so far through the variational approach provide theoretical support for various experiments. Recently introduced ohmic like spectral density function that can account for logarithmic perturbations provides generality and exposition to a unique and practical set of environments. In this paper, we exploit the energy transfer dynamics of a two-level system attached to an ohmic like spectral density function with logarithmic perturbations using a variational polaron transformed master equation. Our results demonstrate that even for a relatively large bath coupling strength, quantum coherence effects can be increased by introducing logarithmic perturbations of the order of one and two in super-ohmic environments. Moreover, for particular values of the ohmicity parameter, the effect of logarithmic perturbations is observed to be insignificant for the overall dynamics. In regard to ohmic environments, as logarithmic perturbations increase, damping characteristics of the coherent transient dynamics also increase in general. It is also shown that, having logarithmic perturbations of the order of one in an ohmic environment can result in a less efficient energy transfer for relatively larger system bath coupling strengths.


Biomechanical effects of unipedicular vertebroplasty on intact vertebrae.
To assess the biomechanical effects of unipedicular vertebroplasty on nonfractured vertebrae. To evaluate the potential benefits of vertebroplasty as a preventative treatment. To evaluate the effects of cement volume and bone mineral density on the mechanics of augmented intact vertebral bodies. Many studies have been undertaken to examine the effects of augmentation procedures such as vertebroplasty or kyphoplasty on fractured vertebral bodies. However, the role of such procedures as a prophylactic or interventional tool has not been well studied. This approach may be of clinical interest due to the high occurrence of secondary compression fractures and potentially altered biomechanics following an isolated vertebroplasty procedure. Nonfractured osteoporotic vertebrae were measured to calculate volume and DEXA scanned to obtain bone mineral density information. Randomly selected specimens were injected with 10% and 20% bone cement by volume or left unfilled to serve as controls. After radiographs and noted cement leakage, specimens were subjected to destructive compression testing. It was found that the injection of 20% bone cement by volume in the lumbar levels resulted in a statistically significant 36% strength increase as compared with the unfilled controls regardless of density levels. However, in the upper thoracic vertebrae there was no significant difference between the strengths of the three groups. Additionally, injection of 20% bone cement frequently resulted in extravasation through vascular channels or into the spinal canal. The introduction of 20% bone cement by volume results in a significant increase in the compressive strength of intact lumbar vertebrae, however upper thoracic vertebrae do not demonstrate a similar strength improvement. There was no difference in the stiffness of the vertebrae injected with cement regardless of location. Bone mineral density (BMD) may play a role in the magnitude of the strength increase, with lower BMD specimens realizing a relatively greater strength improvement. Cement leakage was frequently noted with 20% cement injection, especially in the specimens with higher BMD. The location of the cement did not appear to have an effect on the loading behavior of the bone but should be controlled to minimize the chance of cement escaping into the spinal canal.


Preoperative accelerated radiotherapy combined with chemotherapy in a defined cohort of patients with high risk soft tissue sarcoma: a Scandinavian Sarcoma Group study.
We recently reported outcomes from a Scandinavian Sarcoma Group adjuvant study (SSG XX group A) conducted on localized and operable high risk soft tissue sarcoma (STS) of the extremities and trunk wall. SSG XX, group B, comprised of patients in a defined cohort with locally advanced STS considered at high risk for intralesional surgery. These patients received preoperative accelerated radiotherapy, together with neoadjuvant and adjuvant chemotherapy. Herein we report the results of this group B. Twenty patients with high-grade, locally advanced and deep STS located in lower extremities (n = 12), upper extremities (5) or trunk wall (3) were included. The median age was 59 years and 14 patients were males. The treatment regimen consisted of 6 cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2), with three cycles given neoadjuvantly, and preoperative radiotherapy (1, 8 Gyx2/daily to 36 Gy) between cycles 2 and 3. After a repeated MRI surgery was then conducted, and the remaining 3 chemotherapy cycles were given postoperatively at 3 weeks intervals. Survival data, local control, toxicity of chemotherapy and postoperative complications are presented. Median follow-up time for metastasis-free survival (MFS) was 2.8 years (range 0.3-10.4). The 5-year MFS was 49.5% (95% confidence interval [CI] 31.7-77.4). The median follow-up time was 5.4 years (range 0.3-10.4) for overall survival (OS). The 5-year OS was 64.0% (95% CI 45.8-89.4). The median tumour size was 13 cm, with undifferentiated pleomorphic sarcoma (n = 10) and synovial sarcoma (n = 6) diagnosed most frequently. All patients completed surgery. Resection margins were R0 in 19 patients and R1 in 1 patient. No patients had evidence of disease progression preoperatively. Three patients experienced a local recurrence, in 2 after lung metastases had already been diagnosed. Eleven patients (55%) had postoperative wound problems (temporary in 8 and persistent in 3). Preoperative chemotherapy and radiotherapy were associated with temporary wound-healing problems. Survival outcomes, local control and toxicities were deemed satisfactory when considering the locally advanced sarcoma disease status at primary diagnosis. Trial registration This study was registered at ClinicalTrials.gov Identifier NCT00790244 and with European Union Drug Regulating Authorities Clinical Trials No. EUDRACT 2007-001152-39.


Alteration of floral organ identity by over-expression of IbMADS3-1 in tobacco.
The MADS-box genes have been studied mainly in flower development by researching flower homeotic mutants. Most of the MADS-box genes isolated from plants are expressed exclusively in floral tissues, and some of their transcripts have been found in various vegetative tissues. The genes in the STMADS subfamily are important in the development of whole plants including roots, stems, leaves, and the plant vascular system. IbMADS3-1, which is in the STMADS subfamily, and which has been cloned in Ipomoea batatas (L.) Lam., is expressed in all vegetative tissues of the plant, particularly in white fibrous roots. Sequence similarity, besides the spatial and temporal expression patterns, enabled the definition of a novel MADS-box subfamily comprising STMADS16 and the other MADS-box genes in STMADS subfamily expressed specifically in vegetative tissues. Expression of IbMADS3-1 was manifest by the appearance of chlorophyll-containing petals and production of characteristic changes in organ identity carpel structure alterations and sepaloidy of the petals. In reverse transcription-polymerase chain reaction analysis with a number of genes known to be key regulators of floral organ development, the flowering promoter NFL1 was clearly reduced at the RNA level compared with wild type in transgenic line backgrounds. Moreover, NtMADS5 showed slight down-regulation compared with wild-type plants in transgenic lines. These results suggest that IbMADS3-1 could be a repressor of NFL1 located upstream of NtMADS5. IbMADS3-1 ectopic expression is suggested as a possible means during vegetative development by which the IbMADS3-1 gene may interfere with the floral developmental pathway.


Relocation facilitates the acquisition of short cis-regulatory regions that drive the expression of retrogenes during spermatogenesis in Drosophila.
Retrogenes are functional processed copies of genes that originate via the retrotranscription of an mRNA intermediate and often exhibit testis-specific expression. Although this expression pattern appears to be favored by selection, the origin of such expression bias remains unexplained. Here, we study the regulation of two young testis-specific Drosophila retrogenes, Dntf-2r and Pros28.1A, using genetic transformation and the enhanced green fluorescent protein reporter gene in Drosophila melanogaster. We show that two different short (<24 bp) regions upstream of the transcription start sites (TSSs) act as testis-specific regulatory motifs in these genes. The Dntf-2r regulatory region is similar to the known β2 tubulin 14-bp testis motif (β2-tubulin gene upstream element 1 [β2-UE1]). Comparative sequence analyses reveal that this motif was already present before the Dntf-2r insertion and was likely driving the transcription of a noncoding RNA. We also show that the β2-UE1 occurs in the regulatory regions of other testis-specific retrogenes, and is functional in either orientation. In contrast, the Pros28.1A testes regulatory region in D. melanogaster appears to be novel. Only Pros28.1B, an older paralog of the Pros28.1 gene family, seems to carry a similar regulatory sequence. It is unclear how the Pros28.1A regulatory region was acquired in D. melanogaster, but it might have evolved de novo from within a region that may have been preprimed for testes expression. We conclude that relocation is critical for the evolutionary origin of male germline-specific cis-regulatory regions of retrogenes because expression depends on either the site of the retrogene insertion or the sequence changes close to the TSS thereafter. As a consequence we infer that positive selection will play a role in the evolution of these regulatory regions and can often act from the moment of the retrocopy insertion.


Enhancing effect of polysaccharides from an edible brown alga, Hijikia fusiforme (Hijiki), on release of tumor necrosis factor-alpha from macrophages of endotoxin-nonresponder C3H/HeJ mice.
An enhancing activity for the release of tumor necrosis factor-alpha from macrophages of C3H/HeJ mice was detected in the hot water-soluble extract of an edible brown alga, Hijikia fusiforme (Hijiki in Japanese). This activity was divided into the polysaccharide and nonpolysaccharide fractions, with the former showing much higher activity than the latter. The active components in the polysaccharide fraction were further purified by ion-exchange column chromatography and gel permeation system of high-performance liquid chromatography; they were identified as polysaccharides with apparent molecular mass of about 2,000 and 70 kDa and were designated Hijiki-derived polysaccharides I and II (HPS-I and HPS-II), respectively. They also enhanced macrophage-dependent suppression against the growth of EL-4 tumor cells in an in vitro culture experiment, with HPS-I exhibiting much higher immunologic activity than HPS-II. Furthermore, other comparative experiments confirmed that the immunoenhancing activities of polysaccharides from H. fusiforme are associated with the functions of polysaccharides themselves, but not with the artificial activity induced by contaminated endotoxins. Some biochemical properties of immunoenhancing polysaccharides were partially characterized, and the significance of this finding is discussed from the viewpoint of the protective role of edible seaweeds against carcinogenesis.


Feature selection methods in QSAR studies.
A quantitative structure-activity relationship (QSAR) relates quantitative chemical structure attributes (molecular descriptors) to a biological activity. QSAR studies have now become attractive in drug discovery and development because their application can save substantial time and human resources. Several parameters are important in the prediction ability of a QSAR model. On the one hand, different statistical methods may be applied to check the linear or nonlinear behavior of a data set. On the other hand, feature selection techniques are applied to decrease the model complexity, to decrease the overfitting/overtraining risk, and to select the most important descriptors from the often more than 1000 calculated. The selected descriptors are then linked to a biological activity of the corresponding compound by means of a mathematical model. Different modeling techniques can be applied, some of which explicitly require a feature selection. A QSAR model can be useful in the design of new compounds with improved potency in the class under study. Only molecules with a predicted interesting activity will be synthesized. In the feature selection problem, a learning algorithm is faced with the problem of selecting a relevant subset of features upon which to focus attention, while ignoring the rest. Up to now, many feature selection techniques, such as genetic algorithms, forward selection, backward elimination, stepwise regression, and simulated annealing have been used extensively. Swarm intelligence optimizations, such as ant colony optimization and partial swarm optimization, which are feature selection techniques usually simulated based on animal and insect life behavior to find the shortest path between a food source and their nests, recently are also involved in QSAR studies. This review paper provides an overview of different feature selection techniques applied in QSAR modeling.


Outstanding insecurities concerning the use of an Ov16-based ELISA in the Amazonia onchocerciasis focus.
In a recent issue of Memórias do Instituto Oswaldo Cruz, published in Rio de Janeiro in February 2014 (109: 87-92), Adami et al. have published a survey reporting Mansonella parasite prevalence in the Amazon Region. This report makes a useful contribution to the existing knowledge of filarial parasite distribution within the Amazon area, parasite prevalence rates in relation to age and occupation and provides observations on the possible clinical impact of Mansonella ozzardi. Their publication also provides an account of what appears to be a novel ELISA that has recently been used in the Simuliidae and Onchocerciasis Laboratory of the Oswaldo Cruz Institute, Rio de Janeiro, Brazil. We are concerned that the publication of this ELISA may have created an excessively positive impression of the effectiveness of the onchocerciasis recrudescence serological surveillance tools that are presently available for use in the Amazonia onchocerciasis focus. In this letter we have, thus, sought to highlight some of the limitations of this ELISA and suggest how continuing insecurities concerning the detection of antibodies to Onchocerca volvulus within the Amazonia onchocerciasis focus might be minimised.


Fouling control of a membrane coupled photocatalytic process treating greywater.
Fouling in membrane coupled photocatalytic reactors was investigated in the case of greywater treatment by establishing the link between product type, dose, irradiation time and fouling rates in a cross flow membrane cell fitted with a 0.4 microm pore sized polyethylene membrane. Rapid fouling occurred only with shower gels and conditioners and was linked to changes in the organo-TiO(2) aggregate size postulated to be caused by polymers within the products. Fouling was reduced to a negligible level when sufficient irradiation was applied demonstrating that the membrane component of the process is not the issue and that scale up and implementation of the process relates to effective design of the UV reactor.


Comparison of fecal glucocorticoid metabolite concentrations in hand- versus parent-reared whooping cranes (Grus americana).
Endangered whooping cranes (Grus americana) have been produced in captivity for reintroduction programs since the 1980s, using techniques such as artificial insemination, multiple clutching, and captive-rearing to speed recovery efforts. Chicks are often hand-reared (HR) by caretakers in crane costumes, socialized into groups and released together, unlike parent-reared (PR) cranes that are raised individually by a male/female crane pair and released singly. HR cranes historically exhibit greater morbidity rates during development than PR cranes, involving musculoskeletal and respiratory system disease, among others. We hypothesized that HR crane chicks exhibit a higher baseline fecal glucocorticoid metabolite (FGM) concentrations during the development compared with PR chicks. Fecal samples were collected between 15 and 70 days of age from HR (n = 15) and PR (n = 8) chicks to test for differences in FGM concentrations using a radioimmunoassay technique following ethanol extraction for steroids. Linear mixed model analysis suggests increasing age of the chick was associated with an increase in FGM (p < .001). Analysis also supported the interaction between rearing strategy and sex of the crane chick (p < .01). Female PR chicks had greater FGM concentrations than all other groups (PR male, p < .01; HR female, p < .001; and HR male, p < .001). This result suggests that there may be an effect of rearing strategy on stress physiology of whooping crane chicks, especially among females. Further research is needed to investigate whether the FGM concentrations are reflective of true differences in stress physiology of young cranes and whether this may impact health and conservation success.


Drosophila models of Alzheimer's disease: advances, limits, and perspectives.
Amyloid-β protein precursor (AβPP) and the microtubule-associated protein tau (MAPT) are the two key players involved in Alzheimer's disease (AD) and are associated with amyloid plaques and neurofibrillary tangles respectively, two key hallmarks of the disease. Besides vertebrate models, Drosophila models have been widely used to understand the complex events leading to AD in relation to aging. Drosophila benefits from the low redundancy of the genome which greatly simplifies the analysis of single gene disruption, sophisticated molecular genetic tools, and reduced cost compared to mammals. The aim of this review is to describe the recent advances in modeling AD using fly and to emphasize some limits of these models. Genetic studies in Drosophila have revealed some key aspects of the normal function of Appl and Tau, the fly homologues of AβPP and MAPT that may be disrupted during AD. Drosophila models have also been useful to uncover or validate several pathological pathways or susceptibility genes, and have been readily implemented in drug screening pipelines. We discuss some limitations of the current models that may arise from differences in structure of Appl and Tau compared to their human counterparts or from missing AβPP or MAPT protein interactors in flies. The advent of new genome modification technologies should allow the development of more realistic fly models and to better understand the relationship between AD and aging, taking advantage of the fly's short lifespan.


Fluoride containing bioactive glass composite for orthodontic adhesives - ion release properties.
Dental materials that release calcium, phosphate and fluoride ions could prevent demineralisation and/or enhance remineralisation of enamel. The objective was to develop a novel bioactive glass (BAG) resin and investigate pH changes and ion release in 3 immersion media. Quench melt derived BAG (35.25% SiO2, 6% Na2O, 43% CaO, 5.75% P2O5, and 10% CaF2) was incorporated into a resin (42.25% BisEMA, 55% TEGDMA, 0.25% DMAEM, 0.5% camphorquinone and 2% 4-Meta), with a filler load of 80% by weight. Ninety composite disks for each BAG loading of 80%, 60%, 50%, 40%, 20%, and 0% were made and each disk was immersed in 10ml of either tris buffer (TB), or artificial saliva at pH=7 (AS7) or pH=4 (AS4), n=30 for each solution. Three disks of each loading were taken from each of the solutions, at ten time points (6h-6months), for measurement of pH, fluoride, calcium and phosphate. The BAG adhesive raised the pH in all the solutions, release Ca, PO4 and F ions especially in AS4. The rise in pH and the release of Ca and F are directly related to the BAG loading and the time of immersion. The pH and the ion releases were maintained and continued over 6months. Unlike glass ionomer resins, favourable ions F, Ca and PO4 releases were maintained over a long time period especially in acidic condition for this novel BAG-resin composite. This indicates the resin has the potential to prevent formation and progression of early caries lesions.


Comparison of structure and organization of cutaneous lipids in a reconstructed skin model and human skin: spectroscopic imaging and chromatographic profiling.
The use of animals for scientific research is increasingly restricted by legislation, increasing the demand for human skin models. These constructs present comparable bulk lipid content to human skin. However, their permeability is significantly higher, limiting their applicability as models of barrier function, although the molecular origins of this reduced barrier function remain unclear. This study analyses the stratum corneum (SC) of one such commercially available reconstructed skin model (RSM) compared with human SC by spectroscopic imaging and chromatographic profiling. Total lipid composition was compared by chromatographic analysis (HPLC). Raman spectroscopy was used to evaluate the conformational order, lateral packing and distribution of lipids in the surface and skin/RSM sections. Although HPLC indicates that all SC lipid classes are present, significant differences are observed in ceramide profiles. Raman imaging demonstrated that the RSM lipids are distributed in a non-continuous matrix, providing a better understanding of the limited barrier function.


Serum neopterin and beta 2-microglobulin concentrations in monoclonal gammopathies.
Serum neopterin and beta 2-microglobulin concentrations were investigated in 46 patients with multiple myeloma and in 28 patients with asymptomatic monoclonal gammopathy followed for long periods (median 9.6 years) and showing an absence of evolution. Seventy-two per cent of the patients with multiple myeloma showed beta 2-microglobulin concentrations higher than 3 mg/l with a mean of 6.84 mg/l, whereas all the patients with asymptomatic monoclonal gammopathies had concentrations lower than 3 mg/l with a mean of 1.64 mg/l. Concerning serum neopterin concentrations, 91% of the patients with multiple myeloma had values with in pathological limits (greater than 8 nmol/l) with a mean of 34 nmol/l, whereas all but one of the patients with asymptomatic monoclonal gammopathy had normal values with a mean of 5.19 nmol/l. The differences thus observed in these two groups of patients are highly significant (p less than 0.001). Serum neopterin concentration, unrelated to renal insufficiency, seems to be useful in the differentiation of malignant or benign asymptomatic monoclonal gammopathies.


[The structure of type 2 diabetes risk-factors in people with normal weight].
In the current study we have presented the analyzed data of screening materials of type 2 diabetes patients aged 45 and above carried out in Kharkov (n=535) and Kharkov district villages (n=1052). It has been established, that the data of cohort people with normal body mass index were practically the same and accounted approximately one fourth of the analyzed patients. At the same time, it appeared that the patients living in the city were more susceptible to metabolic obesity (enlargement of abdominal fat tissue), arterial hypertension, myocardial infarction, insult and heavy family history. Metabolic obesity prevalent in city cohorts practically did not have any effect on the frequency of the above mentioned risk-factors. However, it definitely affected the cardio-vascular component in village cohorts.


The Prevalence of Sleep Apnea in Type B Aortic Dissection: Implications for False Lumen Thrombosis.
Obstructive sleep apnea (OSA) has been implicated in aortic dissection. Thrombosis of the false lumen is associated with a prognosis of type B aortic dissection (AoD), and partial thrombosis has been reported to be an independent predictor of mortality. This study sought to explore whether the severity of OSA is associated with false lumen thrombosis. In this observational study, 151 type B AoD patients were recruited consecutively from 2013 to 2015. The status of the false lumen was classified as patent, partially thrombosed, or completely thrombosed based on a computer tomography angiography image. Patients were divided into non-OSA group (apnea-hypopnea index [AHI] < 5), and mild (5 ≤ AHI ≤ 15), moderate (15 < AHI ≤ 30), and severe OSA groups (AHI > 30) using the AHI. The prevalence of OSA in type B dissection was 66.2%. Among 151 cases, 51 patients (33.8%) were in the non-OSA group, 56 (37.1%) were in the mild group, 21 (13.9%) were in the moderate group, and 23 (15.2%) were in the severe group. Additionally, a partially thrombosed false lumen was observed in 88 patients (58.3%). Multivariable analysis revealed that OSA severity was positively associated with partial thrombosis (odds ratio, 1.784, 95% confidence interval: 1.182-2.691, P = .006) after adjusting for other confounding factors. OSA was present in two-thirds of patients with type B AoD. The severity of OSA was significantly associated with an increased risk of partial false lumen thrombosis. OSA may therefore be implicated in both the etiology and prognosis of AoD.


Palm oil supply chain factors impacting chlorinated precursors of 3-MCPD esters.
Chlorinated compounds such as sphingolipid-based organochlorine compounds are precursors for the formation of 3-monochlororopanediol (3-MCPD) esters in palm oil. This study evaluates the effects of several factors within the palm oil supply chain on the levels of sphingolipid-based organochlorine, which in turn may influence the formation of 3-MCPD esters during refining. These factors include application of inorganic chlorinated fertiliser in the oil palm plantation, bruising and degradation of oil palm fruits after harvest, recycling of steriliser condensate as water for dilution of crude oil during oil palm milling, water washing of palm oil and different refining conditions. It was observed that bruised and degraded oil palm fruits showed higher content of sphingolipid-based organochlorine than control. In addition, recycling steriliser condensate during milling resulted in elevated content of sphingolipid-based organochlorine in palm oil. However, the content of sphingolipid-based organochlorine compounds was reduced by neutralisation, degumming and bleaching steps during refining. Although water washing of crude palm oils (CPO) prior to refining did not reduce the content of sphingolipid-based organochlorine, it did reduce the formation of 3-MCPD esters through the removal of water-soluble chlorinated compounds. It was found that the use of inorganic chlorinated fertiliser in plantations did not increase the content of chlorinated compounds in oil palm fruits and extracted oil, and hence chlorinated fertiliser does not seem to play a role in the formation of 3-MCPD esters in palm oil. Overall, this study concluded that lack of freshness and damage to the fruits during transport to mills, combined with water and oil recycling in mills are the major contributors of chlorinated precursor for 3-MCPD esters formation in palm oil.


[Translocation of transposons Tn10 and Tn5 in the Yersinia pestis chromosome].
The possibility of translocation of the transposons Tn5 and Tn10 into the genome of Yersinia pestis, with the subsequent mutagenic effect was demonstrated. We revealed transposon harbouring clones at frequency 10(-4) to 10(-2). Derivatives of P1cml clr100ts phage served as vectors. Insertion of Tn10 transposon induced mutations in ilv, ser, arg, pur, pro, leu, nic, tyr, gua genes. The number of the insertion sites on the chromosome obtained for Tn5 was the same, these being arg, ade, pyr, leu, gua, trp, his, pan, ilv. The majority of auxotrophs did not revert. Occasionally, revertants were observed at frequencies 10(-8) to 10(-6). Unlike Escherichia coli, reversion was not accompanied by the loss of transposons. The rearrangements induced by transposons, presumably, near the insertion site, as well as duplications of transposons followed by incorporation of copies into novel sites, led to the appearance of additional defective genes, which made it possible to select various types of polyauxotrophs. Based on reiteration of coinciding double and triple mutant markers, we proposed a linkage group of genes within a segment of Y. pestis chromosome: lys ... tyr - ser - arg - ilv - leu - gua - ade(pur) - pro ... his ... pyr ... trp. The reasons for peculiarities of the behaviour of transposons in Y. pestis bacteria are discussed.


Cardiac structure and function in fetuses of mothers infected with HIV: the prospective PCHIV multicenter study.
This study was designed to determine if vertically transmitted HIV infection and maternal infection with HIV are associated with altered cardiovascular structure and function in utero. Fetal echocardiography was performed in 173 fetuses of 169 HIV-infected mothers (mean gestational age, 33.0 weeks; SD = 3.7 weeks) at 5 centers. Biparietal diameter, femur length, cardiovascular dimensions, and Doppler velocities through atrioventricular and semilunar valves and the umbilical artery were measured. Measurements were converted to z scores based on published normal data. Fetuses determined after birth to be HIV-infected had similar echocardiographic findings as fetuses later determined to be HIV-uninfected except for slightly smaller left ventricular diastolic dimensions (P =.01). The femur length (P =.03) was also smaller in the fetuses postnatally identified as HIV-infected. Differences in cardiovascular dimensions and Doppler velocities were identified between fetuses of HIV-infected women and previously published normal fetal data. The reason for the differences may be a result of maternal HIV infection, maternal risk factors, or selection bias in the external control data. Vertically transmitted HIV infection may be associated with reduced left ventricular size but not with altered cardiac function in utero. Fetuses of HIV-infected mothers may have abnormal cardiovascular structure and function and increased placental vascular resistance, regardless of whether the fetuses are subsequently found to be infected with HIV.


Posterior malleolus fractures: worth fixing.
The posterior malleolus component of a fracture of the ankle is important, yet often overlooked. Pre-operative CT scans to identify and classify the pattern of the fracture are not used enough. Posterior malleolus fractures are not difficult to fix. After reduction and fixation of the posterior malleolus, the articular surface of the tibia is restored; the fibula is out to length; the syndesmosis is more stable and the patient can rehabilitate faster. There is therefore considerable merit in fixing most posterior malleolus fractures. An early post-operative CT scan to ensure that accurate reduction has been achieved should also be considered. Cite this article: Bone Joint J 2017;99-B:1413-19.


A role for platelet TRPC channels in the Ca2+ response that induces procoagulant activity.
After vascular injury, platelets are rapidly activated by collagen and other agonists, causing them to adhere and aggregate to prevent blood loss. In addition, phosphatidylserine (PS) exposure on the platelet surface accelerates thrombin formation by the coagulation pathway. Thrombin is a potent platelet agonist and converts fibrinogen to fibrin, thereby stabilizing the platelet plug. PS exposure during hemostasis and thrombosis results from a sustained cytosolic Ca(2+) increase; however, the underlying Ca(2+) mobilization pathways have remained unclear. Store-operated Orai1 channels provide substantial, prolonged Ca(2+) influx after inositol trisphosphate-dependent release, and anoctamin 6 (TMEM16F) may operate as a Ca(2+)-activated, Ca(2+)-permeable channel in addition to its scramblase activity that exteriorizes PS. A new study shows that Na(+) entry, resulting from coactivation of the transient receptor potential (TRP) nonselective cation channels TRPC3 and TRPC6, followed by reverse-mode operation of Na(+)/Ca(2+) exchangers, is an important mechanism for the increase in cytosolic Ca(2+) that triggers PS exposure, particularly during combined thrombin and collagen stimulation.


Necessary role for ventral tegmental area adenylate cyclase and protein kinase A in induction of behavioral sensitization to intraventral tegmental area amphetamine.
In the present study, we investigated the effects of selective activation or inhibition of ventral tegmental area (VTA) adenylate cyclase (AC) and protein kinase A (PKA) on long-term sensitization induced by repeated intra-VTA or peripheral amphetamine (AMPH). Selective inhibition of AC by SQ 22,536 (9-(tetrahydro-2-furanyl)-9H-purin-6-amine; 100 nmol/side bilateral into VTA) had no effect on acute basal locomotion but attenuated the locomotor stimulation induced by acute i.p. AMPH (1.5 mg/kg). Coinjection of SQ 22,536 (100 nmol/side) fully blocked the sensitization induced by repeated intra-VTA AMPH (15 nmol/side) but had no detectable effect on the sensitization induced by repeated i. p. AMPH. Persistent activation of AC by intra-VTA cholera toxin (500 ng/side) modestly increased acute locomotion and induced a robust sensitization to i.p. AMPH challenge 10 days after the last of three repeated VTA microinjections. Selective inhibition of PKA by Rp-adenosine-3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPS; 25 nmol/side) had no effect on acute basal or AMPH-stimulated locomotion. Coinjection of Rp-cAMPS (25 nmol/side) fully blocked the sensitization induced by repeated intra-VTA AMPH but had no effect on sensitization induced by repeated i.p. AMPH. Intra-VTA microinjection of the selective PKA activator Sp-adenosine-3',5'-cyclic monophosphothioate triethylamine (Sp-cAMPS; 25-100 nmol/side) dose-dependently stimulated acute locomotion and exerted synergistic effects on locomotor activity when coinfused into the VTA with AMPH but had no detectable effect on acute i.p. AMPH-induced locomotion. Repeated intra-VTA Sp-cAMPS did not induce sensitization to AMPH challenge but potentiated the sensitization induced by repeated i.p. AMPH. These results suggest that VTA cAMP signal transduction is necessary for the induction of persistent sensitization to intra-VTA amphetamine and that peripheral and intra-VTA AMPH may not induce behavioral sensitization by identical mechanisms.


C-reactive protein response to a vegan lifestyle intervention.
This brief lifestyle intervention, including a vegan diet rich in fresh fruits and vegetables, whole grains and various legumes, nuts and seeds, significantly improved health risk factors and reduced systemic inflammation as measured by circulating CRP. The degree of improvement was associated with baseline CRP such that higher levels predicted greater decreases. The interaction between gender and baseline CRP was significant and showed that males with higher baseline CRP levels appeared to have a more robust decrease in CRP due to the intervention than did their female counterparts. It is likely that the vegetable and high fiber content of a vegan diet reduces CRP in the presences of obesity. Neither the quantity of exercise nor the length of stay was significant predictors of CRP reduction. Additionally, those participants who had a vegan diet prior to the intervention had the lowest CRP risk coming into the program. Direct measure of body fat composition, estrogen and other inflammatory mediators such as IL-6 and TNF-alpha would enhance current understanding of the specific mechanisms of CRP reduction related to lifestyle interventions.


[Fast spin echo imaging of vertebral metastasis: comparison of fat suppression techniques (FSE-CHESS, STIR-FSE)].
To investigate the capabilities of fast spin echo (FSE) sequences in diagnosing spinal metastases and to compare two fat-suppression techniques: CHESS (chemical shift selective saturation) and STIR (short T1 inversion recovery). Fat suppression is recommended with FSE sequences because on them, different from conventional spin echo (SE) sequences, fat has high signal intensity in both T1 and T2 weighting, masking such high-signal bone lesions as metastases. Ninety metastatic lesions in 32 patients were studied with T1-weighted SE and T2-weighted FSE sequences with and without fat suppression (FSE-CHESS and STIR-FSE). Quantitative analyses (metastasis size, signal intensity, margins and conspicuity) and qualitative analyses (artifacts and fat saturation homogeneity) were carried out of both fat-suppression sequences. Signal-to-noise (S/N) and contrast-to-noise (C/N) ratios were calculated in 20 metastatic lesions. The results were analyzed with the chi 2 method and the paired t-test. Both fat-suppression FSE sequences were more sensitive to focal lesions (100%) than T1-weighted SE sequences (96.6%). Lesion signal was higher than that of surrounding bone in 95.5% of fat-suppressed images, which facilitated the recognition of spinal metastases. On the contrary, conspicuity was higher (73.3%) and the margins more definite (68.8%) on T1-weighted SE than on T2-weighted FSE sequences. Fat suppression was more apparent on STIR-FSE than on FSE-CHESS sequences, even with no significant difference in C/N ratio. Both STIR-FSE and FSE-CHESS sequences are rapid and useful techniques to obtain fat saturation in FSE images. CHESS saturation is selective on fat signal, while STIR suppresses the signal of all the substances with the same short T1 as fat.


Species diversity in the immunogenetic relationship between mother and fetus: is trophoblast insusceptibility to immunological destruction the only essential common feature for the maintenance of allogeneic pregnancy?
Maternal-fetal immune interactions in pregnancy have been examined in a number of different species using a wide range of experimental procedures, many of which have been incapable of providing information on the specificity of the immunological parameters measured. As a result, data have often been unconvincing, unsubstantiated or conflicting. It is clear that considerable species diversity exists in the precise nature of the maternal immune responses elicited against the genetically dissimilar fetus. These may, however, be an irrelevant consequence of fetomaternal genetic incompatibilities. A feature common to all eutherian mammalian species, that could alone be responsible for the maintenance of allogeneic pregnancy, is the apparent insusceptibility of the fetal trophoblast to immune destruction. This is effected in some species by an absence of appropriate target molecules, particularly classical class I MHC antigens, on the trophoblast cell surface, and in others possessing these (and possibly other) target structures, by the local trophoblastic secretion of soluble factors, not yet fully characterised, that appear to be capable of inhibiting binding and interaction with cells of the maternal immune system. As there is no convincing evidence for transplacental transfer of significant numbers of maternal lymphocytes, the survival of the allogeneic fetus is likely to be ensured by the impenetrability of the trophoblastic tissue barrier and its resistance to maternal immunologically mediated attack. Should this be firmly established, it would not be necessary to invoke any of the immunoregulatory mechanisms that have been claimed to be essential for successful implantation and development of the mammalian embryo. This would in turn negate the concept of an alloimmune aetiology for pregnancy failure and hence also the rationale for those therapeutic procedures intended to restore the assumed inadequate maternal alloimmune protective responses.


1H nuclear magnetic resonance studies on the structure and mechanism of the HPr protein of Staphylococcus aureus.
1H NMR studies of the phosphocarrier protein HPr and its three nitrotyrosyl derivatives revealed some structural features which may finally lead to an explanation of the mechanism of the phospho-transfer reaction. Titration studies on mononitrated, dinitrated, and trinitrated derivatives--i.e., derivatives with Tyr-56, Tyr-56 and Tyr-37, and Tyr-56, Tyr-37, and Tyr-6 modified--have been performed. The three tyrosyl residues seem to be in positions completely different from each other with respect to their solvent accessibility; Tyr-56 seems to be located near the surface of the protein, Tyr-6 seems to be completely buried, and Tyr-37 takes an intermediate position. Tyr-6 contributes to the core structure of the protein. A resonance at -0.18 ppm could be shown to correspond to a CH3 group of a valine. Nuclear Overhauser experiments revealed its being close to Tyr-6. One of the resonances tentatively assigned to methionine SCH3 groups titrates in the dinitrated derivative with the same pK as nitrotyrosyl residue 37. The titration behavior of the active-center histidyl residue suggests a hydrogen bond to the imidazole ring, possibly from Tyr-56 or Arg-17.


Intratumor heterogeneity of k-ras and p53 mutations among human colorectal adenomas containing early cancer.
The molecular pathways and the timing of genetic events during human colorectal carcinogenesis are still not fully understood. We have addressed the intratumor heterogeneity of the mutational status of the k-ras oncogene and of the p53 oncosuppressor gene during the adenoma-carcinoma sequence by investigating 26 human colorectal adenomas containing early cancer. An intratumor comparative analysis was obtained among the adenomatous and carcinomatous component pairs. Additionally, we have analyzed 17 adenomas having cancer in the near vicinity. The adenomatous components of the adenomas containing early cancer and the adenomas having cancer in the near vicinity had comparable frequencies for k-ras mutations (28 and 47%) but different for p53 mutations (52 and 7%, p-value = 0.01). Interestingly, the adenomatous and carcinomatous components of the adenomas containing early cancer were rarely heterogeneous for the k-ras mutational status (only in 13% of the cases) but were characterized by heterogeneity of the p53 status in 59% of the cases (p-value < 0.01). In addition, the mutations of p53 for the adenomatous components of the adenomas containing early cancer were statistically significantly associated with severe dysplasia (p-value = 0.01). Intratumor homogeneity of k-ras status during the human colorectal adenoma-carcinoma sequence suggests that the role of k-ras is more related to tumor initiation than to tumor progression. On the contrary, intratumor heterogeneity of p53 mutations indicates that the type of the p53 mutations may also be relevant for selection and expansion of new subclones leading to tumor progression.


Place and summation coding for canonical and non-canonical finger numeral representations.
Fingers can be used to express numerical magnitudes, and cultural habits about the fixed order in which fingers are raised determine which configurations become canonical and which non-canonical. Although both types of configuration carry magnitude information, it has been shown that the canonical ones are recognized faster and directly linked to number semantics. Here we tested whether this difference is a consequence of differences in the qualitative way of processing the two types of configurations. When participants named Arabic digits (Experiment 1) or verbal numerals (Experiment 2) primed by canonical and non-canonical finger configurations, qualitatively different priming patterns were observed for the two types of configurations. Canonical configurations activated a place coding representation, with priming spreading to close smaller and larger magnitudes as a function of the prime-target distance. Conversely, non-canonical configurations activated a summation coding representation priming smaller and equal magnitudes independently of the prime-target distance, and larger targets depending on this distance.


Recent advances in immunopathophysiology of interleukin-6: an innovative therapeutic drug, tocilizumab (recombinant humanized anti-human interleukin-6 receptor antibody), unveils the mysterious etiology of immune-mediated inflammatory diseases.
Interleukin (IL)-6 cDNA was originally cloned as a terminal B cell differentiation factor into antibody-producing plasma cells. This revealed that it is a multifunctional cytokine that acts on a variety of cells. From the clinical viewpoint, it is especially important that IL-6 acts on hepatocytes to induce acute-phase reactants, including C-reactive protein, serum amyloid A protein, and fibrinogen, and to decrease serum albumin levels. Very recently, this cytokine has been found to enhance the synthesis of a peptide called hepcidin in the liver which regulates iron recycling, resulting in anemia due to hypofferemia. It has also been shown that IL-6 is responsible for various clinical symptoms, including the appearance of autoantibodies, fatigue, anemia, anorexia, fever, and increases in the erythrocyte sedimentation rate, all of which develop in patients with various chronic autoimmune inflammatory diseases. In practice, blocking the IL-6 signaling pathway with a recombinant humanized anti-IL-6 receptor antibody, tocilizumab (TCZ), has dramatically improved all the signs and symptoms of these patients. A study in mice demonstrated that IL-6 promotes the development of a new type of T-helper cells called Th17 cells that impact the pathogenesis of autoimmune diseases. This suggests that TCZ is not only an antiinflammatory agent but also might affect basic autoimmunity. In this review, recent advances in the immunobiology of interleukin-6 related to immune-mediated diseases are discussed.


Deciphering phenotypic diversity of Ralstonia solanacearum strains pathogenic to potato.
Based on the phylotype classification, we questioned how genetically and phenotypically diverse strains of Ralstonia solanacearum pathogenic to potato may be. We studied 129 European and Mediterranean strains along with 57 reference strains known to cover genetic diversity in this species. Phylogeny analysis was done on endoglucanase gene sequences. Pathogenicity to potato, tomato, and eggplant was established at 24 to 30°C and 15 to 24°C, whereas tests on banana were conducted at 24 to 30°C. The ability to cause wilt on species of Solanaceae was shared by strains in all four phylotypes. Brown rot phylotypes IIB-1 and IIB-2 and phylotype IIB-27 established latent infections in banana, and Moko disease-causing phylotypes IIA-6, IIB-3, and IIB-4 were virulent to susceptible potato and tomato, addressing the question of host adaptation mechanisms, which may have undergone a similar bottleneck evolution. Cold-tolerance ability is only shared on species of Solanaceae among brown rot phylotype IIB-1, which gathered the majority of European and Mediterranean strains. We surveyed strain LNPV24.25 as the first report of an emerging phylotype IIB-4NPB strain in France. These findings showed that pathogenicity traits of genetically identified strains still need to be understood, especially in the perspective of post-genomics comparative analysis, to understand bacterial speciation in the R. solanacearum species complex.


Monte Carlo calculations of the dose backscatter factor for monoenergetic electrons.
Recently, there has been growing interest in beta emitters for therapeutic uses, especially in connection with so-called endovascular (or intravascular) brachytherapy. Since accurate dose estimation is necessary for the success of such applications, some problems in beta-ray dosimetry need further study. Among these problems, we have investigated the effect of electron backscattering on dose, which has significance not only for accurate dose estimation but also for new source design. In this study, an empirical measure of electron backscattering, known as the dose backscatter factor, was calculated using EGS4 Monte Carlo calculations for monoenergetic electrons and various scattering materials. Electron energies were 0.1, 0.5, 1.0, 2.0 and 3.0 MeV in combination with Al (Z = 13), Ti (Z = 22), Sr (Z = 38), Ag (Z = 47) and Pt (Z = 78) scatterers. The dose backscatter factor ranged from 10% to 60%, depending on electron energy and material, and was found to increase with the atomic number Z by a log(Z + 1) relationship. A method is presented for calculating the beta-ray dose backscatter factors using the results of this study. To demonstrate the efficacy of this method, a dose backscatter factor depth profile for 32P near a water/aluminium interface was calculated and these calculated results were found to generally reproduce the depth profile obtained from direct EGS4 calculations using the 32P spectrum. The data presented in this study can be used to calculate dose backscatter factors for any combination of beta emitter/scatterer whose atomic number ranges from 13 to 78.


Structural investigations of anthranilimide derivatives by CoMFA and CoMSIA 3D-QSAR studies reveal novel insight into their structures toward glycogen phosphorylase inhibition.
In the present work, three-dimensional quantitative structure-activity relationship (3-D QSAR) studies on a set of 70 anthranilimide compounds has been performed using docking-based as well as substructure-based molecular alignments. This resulted in the selection of more statistically relevant substructure-based alignment for further studies. Further, molecular models with good predictive power were derived using CoMFA (r² = 0.997; Q² = 0.578) and CoMSIA (r² = 0.976; Q² = 0.506), for predicting the biological activity of new compounds. The so-developed contour plots identified several key features of the compounds explaining wide activity ranges. Based on the information derived from the CoMFA contour maps, novel leads were proposed which showed better predicted activity with respect to the already reported systems. Thus, the present study not only offers a highly significant predictive QSAR model for anthranilimide derivatives as glycogen phosphorylase (GP) inhibitors which can eventually assist and complement the rational drug-design attempts, but also proposes a highly predictive pharmacophore model as a guide for further development of selective and more potent GP inhibitors as anti-diabetic agents.


Aesthetic Evaluation and Validation: Umbilicus Reconstruction after DIEP Flap.
The most common method for autologous breast reconstruction is the deep inferior epigastric perforator (DIEP) flap. The umbilicus can be managed in various ways, including re-inset, neo-umbilicus, and umbilectomy without reconstruction. This study evaluated the aesthetic differences in umbilicus reconstruction choice and variation in patients' post-operative satisfaction with their abdomen. A retrospective review of 1019 patients treated with DIEP flap breast reconstruction between August 2009 and January 2022 was conducted. Patients were stratified by management of the umbilicus: preservation and re-inset of the native umbilicus, umbilectomy with delayed reconstruction, and umbilectomy with no reconstruction. A crowd-sourced survey was created to assess the aesthetic preference of each photo using a Likert scale. There were 1063 responses to the umbilicus preference crowdsource survey. Patients who had delayed umbilicus reconstruction after umbilectomy were rated significantly more attractive (4.397 ± 1.697) than both preservation of the native umbilicus (4.176 ± 1.669) and the lack of umbilicus (3.994 ± 1.733) (p < 0.001, p < 0.001, respectively). In an analysis of Breast-Q scores, delayed reconstruction patients had a similar change across measures when compared to the re-inset group. The delayed group had a significantly higher change in overall satisfaction and well-being with abdomen when compared to the no reconstruction group (p = 0.006, p = 0.027, respectively). This study demonstrates that umbilectomy with delayed reconstruction yields a significantly higher aesthetic rating and comparable patient satisfaction when compared to re-inset of the umbilicus.


[Incidence of severe rotavirus gastroenteritis among Chilean children under three years of age].
Rotavirus infections account every year in Chile, for approximately 53,000 emergency consultations and 8,000 hospital admissions among children under three years of age. To estimate incidence rates of severe rotavirus gastroenteritis in children <3 years of age, living in the V and VIII Regions and to identify the predominant viral serotypes. A prospective hospital-based surveillance for severe gastroenteritis was implemented in public and private hospitals of Viña del Mar and Valparaiso (Region V) and of Chiguayante, Concepción, Penco, San Pedro de la Paz, Talcahuano and Tomé (Region VIII). All children <3 years of age residing in the districts, who consulted for severe gastroenteritis requiring oral or intravenous rehydration (equivalent to WHO plan B or C), or who were admitted to the hospital, were enrolled. Demographic and clinical information and a stool sample were obtained. Rotavirus was detected by ELISA and positive samples were serotyped by ELISA or real time PCR. Between January 23 and June 30, 2003, a total of 760 children were recruited. Among these, 343 (45%) were admitted to the hospital. Stool samples were collected from 433 children. Among these, 214 were positive for rotavirus (49.4%). Overall, monthly disease incidence rates were 124/100,000 in V Region, and 114/100,000 in VIII Region. The predominant serotype was G4. Rotavirus was responsible for nearly half of the severe gastroenteritis episodes among children <3 years, during a predominantly G4 serotype season. Every year, approximately one every 70 children <3 years will have a severe rotavirus gastroenteritis episode.


Diagnostic Accuracy of Laryngeal Ultrasound for Evaluating Vocal Fold Movement Impairment in Children.
Vocal fold movement impairment (VFMI) secondary to recurrent laryngeal nerve (RLN) injury is a common source of morbidity after pediatric cervical, thoracic, and cardiac procedures. Flexible laryngoscopy (FL) is the gold standard to diagnose VFMI yet can be challenging to perform and/or risks possible clinical decompensation in some children and is an aerosolizing procedure. Laryngeal ultrasound (LUS) is a potential non-invasive alternative, but limited data exists in the pediatric surgical population regarding its efficacy. We aimed to investigate the diagnostic accuracy of LUS compared to FL in evaluating VFMI. A prospective, single-center, single-blinded (rater) cohort study was undertaken on perioperative pediatric patients at risk for RLN injury. Patients underwent FL and LUS. Cohen's kappa was used to determine chance-corrected agreement. Between 2021 and 2023, 85 paired evaluations were performed with patients having a median (IQR) age of 10 (4, 42) months and weight of 7.5 (5.4, 13.4) kilograms. The prevalence of VFMI was 27.1%. Absolute agreement between evaluations was 98.8% (kappa 0.97, 95% CI: 0.91-1.00, P < 0.001). The sensitivity and specificity of LUS in detecting VFMI was 95.7% and 100%, yielding a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 98.4% (95% CI: 90-100%). Diagnostic accuracy was 98.8% (95% CI: 93-100%). LUS is a highly accurate modality in evaluating VFMI in children. While FL remains the gold standard for diagnosis, LUS offers a low-risk screening modality for children at risk for VFMI such that only those with an abnormal LUS or presence of clinical symptoms discordant with LUS findings should undergo FL. Prospective, single-center, single blinded (rater), cohort study. Level II.


The Edwin Smith papyrus: a clinical reappraisal of the oldest known document on spinal injuries.
Dating from the seventeenth century B.C: . the Edwin Smith papyrus is a unique treatise containing the oldest known descriptions of signs and symptoms of injuries of the spinal column and spinal cord. Based on a recent "medically based translation" of the Smith papyrus, its enclosed treasures in diagnostic, prognostic and therapeutic reasoning are revisited. Although patient demographics, diagnostic techniques and therapeutic options considerably changed over time, the documented rationale on spinal injuries can still be regarded as the state-of-the-art reasoning for modern clinical practice.


Synthesis and biological investigations of some novel thiazolylbenzimidazoles, and benzimidazolyl-thiazolo[4,5-d]pyrimidines.
Several thiazolyl-benzimidazoles 2, 4a-c were synthesized through the reaction of 2-cyanomethyl-1 H-benzimidazole with isothiocyanates followed by cyclization of the produced intermediates 1a-b with either ethyl bormocetate or phenacyl bromides. When the cyclization was performed in alkaline medium, thiophenyl-benzimidazoles 5, 6a, b were produced. Another series of thiazolyl-benzimidazoles 8 a-d was obtained from 2,3-dihydrothiazole-2-(3 H)-thiones 7a-d and 2-cyanomethyl-1 H-benzimidazole, then cyclized to the corresponding thiazolo[4,5-d]pyrimidine 10a-d. Most of the prepared compounds were evaluated for their in-vitro antibacterial, antifungal, anti-HIV and anti-cancer activities. They showed promising antifungal activity.


Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases.
Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment.


The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats.
Zinc compounds have been shown to antagonize various types of gastric ulceration in rats. Zinc carnosine (Z-103), a newly developed agent was, therefore, examined for its antiulcer effect in stress-induced ulceration and also its membrane stabilizing action in rat stomachs. Cold-restraint (restrained at 4 degrees C for 2 h) stress induced severe hemorrhagic lesions together with increased mast cell degranulation and beta-glucuronidase release in the gastric glandular mucosa. Z-103 pretreatment with a single oral dose (3, 10 or 30 mg/kg) reversed these actions in a dose-dependent manner. When the compound was incubated in concentrations of 10(-7, 10(-6), 10(-5) or 10(-4) M, with isolated hepatic lysosomes, it significantly reduced the spontaneous release of beta-glucuronidase in the medium. The present study not only demonstrates the antiulcer effect of Z-103 but also indicates that the protective action is likely to be mediated by its membrane-stabilizing action on mast cells and lysosomes in the gastric glandular mucosa.


Complete nucleotide sequence of a soybean actin gene.
Soybean contains a small multigene family of actin-related sequences. We have determined the complete nucleotide sequence of a soybean actin gene carried on the recombinant plasmid pSAc3. As deduced from the nucleotide sequence, this soybean actin is composed of 376 amino acids. Compared to other eukaryotic actins, pSAc3 actin has a deletion of one amino acid between residues 118 and 122. The initiator methionine is followed by alanine, which is not found at this position in other eukaryotic actins. pSAc3 actin differs, in primary sequence, more from fungal and animal actins than any of the known nonplant actins differ from each other. pSAc3 actin appears to be related to both cytoplasmic and muscle specific actins in the location of specific NH(2)-terminal amino acids. The coding sequence is interrupted by three small introns, each less than 90 base pairs long. The splice junctions are similar to those found in other eukaryotic genes, suggesting the presence of a similar splicing apparatus in higher plants. Introns 1 and 3 interrupt the reading frame after codons 20 and 355, respectively. Intron 2 splits a glycine codon at position 151. None of these intron positions is conserved relative to the positions of introns in other actin genes examined.


Meropenem +/- granulocyte colony stimulating factor in the treatment of febrile neutropenic patients with cancer: prospective randomized study.
The purpose of this study was to evaluate the impact of granulocyte-colony stimulating factor (G-CSF) on the therapy for febrile neutropenia (FN). Our patient population differed significantly from those of previous studies as no patients received antimicrobial or CSF prophylaxis before randomization and all were solid tumor patients. When the diagnosis of FN was established, patients were started on intravenous meropenem 1 g every 8 hours and randomly assigned to receive G-CSF (5 microg/kg body weight per day subcutaneously) or not. Twenty-eight patients with 30 FN episodes received G-CSF and 25 patients with 30 FN episodes did not receive G-CSF according to randomization. The time to resolution of fever, recovery of neutrophil count over 1000/mm3, duration of hospitalization, need for erythrocyte and platelet transfusion and mortality rate were similar in both study groups. Side effects of therapy were mild. These results provide preliminary evidence that G-CSF administration, in addition to effective antibiotic therapy as treatment of febrile neutropenic patients with solid tumor, does not help improve infection-related morbidity and mortality.


A mathematical method for the 3D analysis of rotating deformable systems applied on lumen-forming MDCK cell aggregates.
Cell motility contributes to the formation of organs and tissues, into which multiple cells self-organize. However such mammalian cellular motilities are not characterized in a quantitative manner and the systemic consequences are thus unknown. A mathematical tool to decipher cell motility, accounting for changes in cell shape, within a three-dimensional (3D) cell system was missing. We report here such a tool, usable on segmented images reporting the outline of clusters (cells) and allowing the time-resolved 3D analysis of circular motility of these as parts of a system (cell aggregate). Our method can analyze circular motility in sub-cellular, cellular, multi-cellular, and also non-cellular systems for which time-resolved segmented cluster outlines are available. To exemplify, we characterized the circular motility of lumen-initiating MDCK cell aggregates, embedded in extracellular matrix. We show that the organization of the major surrounding matrix fibers was not significantly affected during this cohort rotation. Using our developed tool, we discovered two classes of circular motion, rotation and random walk, organized in three behavior patterns during lumen initiation. As rotational movements were more rapid than random walk and as both could continue during lumen initiation, we conclude that neither the class nor the rate of motion regulates lumen initiation. We thus reveal a high degree of plasticity during a developmentally critical cell polarization step, indicating that lumen initiation is a robust process. However, motility rates decreased with increasing cell number, previously shown to correlate with epithelial polarization, suggesting that migratory polarization is converted into epithelial polarization during aggregate development.


Upper cervical anterior fusion with a particular focus on superior laryngeal nerve and hypoglossal nerve.
During upper cervical anterior fusion involving C2, the branches of the superior laryngeal and hypoglossal nerves traversing the operative field are at risk for injury, mainly from excessive retraction and/or incidental ligation. These injuries would cause postoperative dysphagia and/or dysphonia that are often transient but might sometimes persist for several months. The aim of this study was to describe our modified approach for upper cervical anterior fusion and to examine the surgical outcomes and postoperative complications in a small case series. Four patients underwent upper cervical anterior fusion at our institution. Detaching the omohyoid and sternohyoid muscles from the hyoid bone increased the mobility of the hyoid bone and enabled visualization of the thyrohyoid membrane. This maneuver facilitated access to C2 without excessive retraction to the larynx and the hypoglossal nerve traversing above the hyoid bone. Moreover, this maneuver enabled easy identification and dissection of the internal branch of the superior laryngeal nerve piercing the thyrohyoid membrane. Three patients underwent C2-3 fusion and one patient underwent C2-5 fusion followed by instrumentation. In all patients, wide, adequate exposure of C2 and proper instrumentation was achieved, and both the internal branch of the superior laryngeal nerve and the hypoglossal nerve were identified and preserved. No patient experienced remarkable postoperative dysphagia, dyspnea, and dysphonia. Solid union was achieved in all patients. The technique of detaching the infrahyoid muscles from the hyoid bone during upper cervical anterior fusion involving C2 reduced the traction force to the larynx and the hypoglossal nerve, enabled easy identification of the internal branch of the superior laryngeal nerve, and prevented postoperative complications, such as dysphagia.


The Plasma Oxylipin Signature Provides a Deep Phenotyping of Metabolic Syndrome Complementary to the Clinical Criteria.
Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Oxylipins are a superfamily of lipid mediators regulating many cardiometabolic functions. Plasma oxylipin signature could provide a new clinical tool to enhance the phenotyping of MetS pathophysiology. A high-throughput validated mass spectrometry method, allowing for the quantitative profiling of over 130 oxylipins, was applied to identify and validate the oxylipin signature of MetS in two independent nested case/control studies involving 476 participants. We identified an oxylipin signature of MetS (coined OxyScore), including 23 oxylipins and having high performances in classification and replicability (cross-validated AUCROC of 89%, 95% CI: 85-93% and 78%, 95% CI: 72-85% in the Discovery and Replication studies, respectively). Correlation analysis and comparison with a classification model incorporating the MetS criteria showed that the oxylipin signature brings consistent and complementary information to the clinical criteria. Being linked with the regulation of various biological processes, the candidate oxylipins provide an integrative phenotyping of MetS regarding the activation and/or negative feedback regulation of crucial molecular pathways. This may help identify patients at higher risk of cardiometabolic diseases. The oxylipin signature of patients with metabolic syndrome enhances MetS phenotyping and may ultimately help to better stratify the risk of cardiometabolic diseases.


Tissue-engineered bone repair of goat-femur defects with osteogenically induced bone marrow stromal cells.
Tissue engineering can generate bone tissue and has been shown to provide a better means of repairing weight-bearing bone defect. Previous studies, however, have heretofore been limited to the use of nonosteogenically induced bone marrow stromal cells (BMSCs) or the application of slow-degradation scaffolds. In this study, weight-bearing bone was engineered using osteogenically induced BMSCs. In addition, coral was used as a scaffold material, due to its proper degradation rate for the engineering and repair of a goat femur defect. A 25 mm long defect was created at the middle of the right femur in each of 10 goats. The rates of defect repair were compared in an experimental group of ten goats receiving implants containing osteogenically induced BMSCs and in the control group of goats (n = 10) receiving just coral cylinders. In the experimental group, bony union was observed by radiographic and gross view at 4 months, and engineered bone was further remodeled into newly formed cortexed bone at 8 months. There was increased gray density of radiographic rays in the repaired area, which was significantly different (p < 0.05) from that of the control group. H&E staining demonstrated that trabecular bone was formed at 4 months. Moreover, irregular osteon was observed at 8 months. Most importantly, the tissue-engineered bone segment revealed a similarity to the left-side normal femur in terms of bend load strength and bend rigidity, showing no significant difference (p > 0.05). In contrast, the coral cylinders of the control group showed no bone formation. Furthermore, almost complete resorption of the carrier had occurred, being evident at 2 months in the control group. H&E staining demonstrated that a small amount of residual coral particle was surrounded by fibrous tissue at 4 months whereas the residues disappeared at 8 months. Based on these results, we conclude that engineered bone from osteogenically induced BMSCs and coral can ideally heal critical-sized segmental bone defects in the weight-bearing area of goats.


NAG-thiazoline is a potent inhibitor of the Vibrio campbellii GH20 β-N-Acetylglucosaminidase.
Vibrio spp. play a vital role in the recycling of chitin in oceans, but several Vibrio strains are highly infectious to aquatic animals and humans. These bacteria require chitin for growth; thus, potent inhibitors of chitin-degrading enzymes could serve as candidate drugs against Vibrio infections. This study examined NAG-thiazoline (NGT)-mediated inhibition of a recombinantly expressed GH20 β-N-acetylglucosaminidase, namely VhGlcNAcase from Vibrio campbellii (formerly V. harveyi) ATCC BAA-1116. NGT strongly inhibited VhGlcNAcase with an IC50 of 11.9 ± 1.0 μm and Ki 62 ± 3 µm, respectively. NGT was also found to completely inhibit the growth of V. campbellii strain 650 with an minimal inhibitory concentration value of 0.5 µm. ITC data analysis showed direct binding of NGT to VhGlcNAcase with a Kd of 32 ± 1.2 μm. The observed ΔG°binding of -7.56 kcal·mol-1 is the result of a large negative enthalpy change and a small positive entropic compensation, suggesting that NGT binding is enthalpy-driven. The structural complex shows that NGT fully occupies the substrate-binding pocket of VhGlcNAcase and makes an exclusive hydrogen bond network, as well as hydrophobic interactions with the conserved residues around the -1 subsite. Our results strongly suggest that NGT could serve as an excellent scaffold for further development of antimicrobial agents against Vibrio infections. DATABASE: Structural data are available in PDB database under the accession number 6K35.


Caring for persons with Dementia: a qualitative study of the needs of carers following care recipient discharge from hospital.
A randomised clinical trial titled the Carer End of Life Planning Intervention (CELPI) in people dying with dementia evaluated the effect of carer education and support about palliative care on care recipient outcomes. We present a pre-planned qualitative analysis of data collected during the CELPI trial in which needs of carers randomised to the study intervention group were assessed using a novel instrument (Carer Needs Directed Assessment in Dementia (CANDID). This tool aimed to identify carers' perceptions of their own and their care-recipients' needs and is an important step in identifying support provision for dementia-specific, palliative cares services upon hospital discharge. The CANDID tool was designed to identify the needs and experiences of primary carers and of their care recipients during the last twelve months of the care recipient's life. The tool consisted of 33 open-ended questions evaluating: symptom management, emergency contacts, advance care planning, carer's perception of the care recipient's future needs, carer's current needs, and a proposed current and future care plan. The researcher's philosophical assumption of interpretative phenomenology informed the study and approach to data collection and analysis. Qualitative data collected during interviews using this tool were thematically analysed in five steps: compiling, disassembling, reassembling, interpreting and concluding. An interpretation of participants' reality emerged from their common experiences and the subjective meanings assigned to actions attached to the phenomena studied. Thirty carer participants were included. Analysis identified three major themes: Carers' perceived stressors, systemic barriers to care provision, and future planning. Issues identified included barriers to accessing supports, carer health and division between roles, financial burden, familial conflicts, adquate care in hospital and aged care facilities, concern about future needs, and end-of-life discussions. The CANDID tool enabled an evaluation of carer needs and concerns. Identifying those needs may inform a referral to palliative care services where the level of management required may be benenficial for both the person living with dementia and their primary carer. Australian Clinical Trials Registration: (ACTRN12619001187134).


Mood Sensitive Stocks and Sustainable Cross-Sectional Returns During the COVID-19 Pandemic: An Analysis of Day of the Week Effect in the Chinese A-Share Market.
This study examines two stock market anomalies and provides strong evidence of the day-of-the-week effect in the Chinese A-share market during the COVID-19 pandemic. Specifically, we examined the Quality minus Junk (QMJ) strategy return on Monday and FridayQuality stocks mean portfolio deciles that earn higher excess returns. As historical evidences suggest that less distressed/safe stocks earn higher excess returns (Dichev, 1998).. The QMJ factor is similar to the division of speculative and non-speculative stocks described by Birru (2018). Our findings provide evidence that the QMJ strategy gains negative returns on Fridays for both anomalies because the junk side is sensitive to an elevated mood and, thus, performs better than the quality side of portfolios on Friday. Our findings are also consistent with the theory of investor sentiment which asserts that investors are more optimistic when their mood is elevated, and generally individual mood is better on Friday than on other days of the week. Therefore, the speculative stocks earned higher sustainable stock returns during higher volatility in Chinese market due to COVID-19. Intrinsically, new evidence emerges on an inclined strategy to invest in speculative stocks on Fridays during the COVID-19 pandemic to gain sustainable excess returns in the Chinese A-share market.


Encoding Molecular Docking for Quantum Computers.
Molecular docking is important in drug discovery but is burdensome for classical computers. Here, we introduce Grid Point Matching (GPM) and Feature Atom Matching (FAM) to accelerate pose sampling in molecular docking by encoding the problem into quadratic unconstrained binary optimization (QUBO) models so that it could be solved by quantum computers like the coherent Ising machine (CIM). As a result, GPM shows a sampling power close to that of Glide SP, a method performing an extensive search. Moreover, it is estimated to be 1000 times faster on the CIM than on classical computers. Our methods could boost virtual drug screening of small molecules and peptides in future.


Arginine modification of lycosin-I to improve inhibitory activity against cancer cells.
Lycosin-I is a linear amphipathic α-helical anticancer peptide (ACP) extracted from the spider Lycosa singoriensis, which can activate the mitochondrial death pathway to induce apoptosis in tumor cells and up-regulate p27 to inhibit cell proliferation. However, the applicability of lycosin-I as a novel anticancer drug is limited by its low cellular entry and efficacy in solid tumors. Amino acid substitution presents an effective and modest strategy to improve the anticancer activity and bioavailability of ACPs. Herein, an arginine-modified lycosin-I (named R-lycosin-I) was designed and synthesized by substituting lysine (Lys) with arginine (Arg). This peptide exhibited higher anticancer activity and penetrability against solid tumor cells than lycosin-I. They displayed noticeable differences in their physicochemical properties including the secondary structure, hydrodynamic size, and zeta potential. Fluorescence analyses have confirmed that R-lycosin-I exhibits increased cellular uptake and improved intracellular distribution. Due to its superior physical and chemical properties and high serum stability, R-lycosin-I could penetrate deeply into tumor spheroids and produce strong toxicity in the 3D tumor model. Overall, these findings suggest that arginine modification may provide an effective strategy for improving the anticancer activity of lycosin-I, and R-lycosin-I may be a useful lead for developing anticancer drugs.


Radio stars.
Up to the present time six classes of radio stars have been established. The signals are almost always very faint and drastically variable. Hence their discovery has owed as much to serendipity as to the highly sophisticated equipment and techniques that have been used. When the variations are regular, as with the pulsars, this characteristic can be exploited very successfully in the search for new objects as well as in the detailed study of those that are already known. The detection of the most erratically variable radio stars, the flare stars and the x-ray stars, is primarily a matter of luck and patience. In the case of the novas, one at least knows where and oughly when to look for radio emission. A very sensitive interferometer is clearly the best instrument to use in the initial detection of a radio star. The fact that weak background sources are frequently present makes it essential to prove that the position of a radio source agrees with that of a star to within a few arc seconds. The potential of radio astronomy for the study of radio stars will not be realized until more powerful instruments than those that are available today can be utilized. So far, we have been able to see only the most luminous of the radio stars.


Carcinogenic activity of the flame retardant, 2,2-bis(bromomethyl)-1,3-propanediol in rodents, and comparison with the carcinogenicity of other NTP brominated chemicals.
Several brominated chemicals have been shown to be multisite-multispecies carcinogens in laboratory animals, and in this paper we report that the flame retardant, 2,2-bis(bromomethyl)-1,3-propanediol (BMP) is also a multisite carcinogen in both sexes of Fischer 344 rats and B6C3F1 mice. BMP was administered continuously in the diet for up to 2 yr to rats at doses of 0, 2,500, 5,000, or 10,000 ppm and to mice at doses of 0, 312, 625, or 1,250 ppm. Interim groups of rats were examined at 15 mo. An additional recovery group of male rats received the chemical for 3 mo at 20,000 ppm in the feed, and then the control diet for the remainder of the study. Chemical exposure caused neoplasms of the skin, subcutaneous tissue, mammary gland, Zymbal's gland, oral cavity, esophagus, forestomach, small intestine, large intestine, mesothelium, kidney, urinary bladder, lung, thyroid gland, seminal vesicle, hematopoietic system, and pancreas in the male rat; mammary gland, oral cavity, esophagus, and thyroid gland in the female rat; lung, kidney, and Harderian gland in male mice; and subcutaneous tissue, lung, and Harderian gland in the female mouse. The recovery group of male rats presented with the same spectrum of treatment-related neoplasms as in the core study. In this recovery group, BMP (at 20,000 ppm) caused irreversible effects at numerous sites after 90 days of exposure that was not detectable by histologic examination, but without further exposure resulted in carcinogenic responses at 2 yr. BMP is mutagenic in the salmonella test, but it was not determined if the BMP-induced effects that eventually lead to development of neoplasms at multiple sites are the same in both species and in all organ systems affected.


[Diagnostic difficulties in lower-lobe tuberculosis].
Lower lobe tuberculosis is diagnosed more frequently than tuberculosis of the superior lobe in subjects seeking medical advice. Clinical improvement achieved by nonspecific antibacterial therapy should not diminish the alertness of the physicians to tuberculosis. When making diagnosis it is necessary to take into consideration: duration of the disease, relatively satisfactory condition in advanced process, negative x-ray picture, contact with tuberculosis patients. Multiple examinations of the sputum for M. tuberculosis are recommended.


Periprosthetic joint infection with streptococcus dysgalactiae subspecies equisimilis: Case report.
Streptococcus dysgalactiae (SD) is a common pathogen among elderly population. However, to our knowledge, there is no periprosthetic joint infection case reported that is infected with Streptococcus dysgalactiae subspecies equisimilis (SDSE) in the English literature. In this article, we report a 77-year-old male patient who had undergone total knee arthroplasty three years ago and had the diagnosis of cellulitis at his leg followed by swelling, pain and hyperemia localized at his knee. Three knee aspirations were performed and the SDSE was identified. There was no direct contact of patient to animals.


Focus on mTOR inhibitors and tacrolimus in renal transplantation: pharmacokinetics, exposure-response relationships, and clinical outcomes.
Mammalian target of rapamycin (mTOR)-inhibitor-containing immunosuppressive regimens have been developed as part of calcineurin inhibitor (CNI) minimization/withdrawal strategies for renal transplant recipients, with the goal of avoiding CNI-associated nephrotoxicity. This review focuses on the pharmacokinetic interactions and exposure-response relationships of mTOR inhibitors and tacrolimus (TAC), the most widely used CNI. We also discuss key randomized clinical studies that have evaluated use of this combination in renal transplantation. Pharmacokinetic studies have shown that mTOR inhibitors, everolimus (EVR) and sirolimus (SRL), have a large intra- and inter-patient variability in drug exposure, and narrow therapeutic windows (trough levels [C0] 3-8 ng/mL and 5-15 ng/mL, respectively). Consequently, routine therapeutic drug monitoring of EVR and SRL is recommended to optimize efficacy and minimize toxicity in individual patients. As there is a good correlation between C0 and area under the curve (AUC), C0 can be used as a convenient and reliable measure of mTOR drug exposure. Clinical data on the use of EVR or SRL in TAC minimization strategies in renal transplantation are limited. Available evidence suggests that treatment with EVR allows early and substantial TAC minimization when used with basiliximab induction and corticosteroids, to achieve good renal function without compromising efficacy or safety. However, data comparing this combination with other regimens are lacking. Results with SRL are more mixed. SRL in combination with reduced TAC has been shown to provide less nephrotoxicity than the SRL/standard TAC combination, with comparable efficacy and safety. However, this approach has been shown to be inferior to other regimens in terms of patient/graft survival and biopsy-proven acute rejection (vs MMF/TAC) as well as renal function (vs MMF/TAC and SRL/MMF). Further studies are needed to define the therapeutic window for TAC when used in combination with mTOR inhibitors, evaluate EVR/reduced TAC versus other regimens, assess long-term outcomes, and determine efficacy and safety in high-risk patients.


Evolution of host life-history traits in a spatially structured host-parasite system.
Most models for the evolution of host defense against parasites assume that host populations are not spatially structured. Yet local interactions and limited dispersal can strongly affect the evolutionary outcome, because they significantly alter epidemiological feedbacks and the spatial genetic structuring of the host and pathogen populations. We provide a general framework to study the evolution of a number of host life-history traits in a spatially structured host population infected by a horizontally transmitted parasite. Our analysis teases apart the selective pressures on hosts and helps disentangle the direct fitness effect of mutations and their indirect effects via the influence of spatial structure on the genetic, demographic, and epidemiological structure of the host population. We then illustrate the evolutionary consequences of spatial structure by focusing on the evolution of two host defense strategies against parasitism: suicide upon infection and reduced transmission. Because they bring no direct fitness benefit, these strategies are counterselected or selectively neutral in a nonspatial setting, but we show that they can be selected for in a spatially structured environment. Our study thus sheds light on the evolution of altruistic defense mechanisms that have been observed in various biological systems.


A morphometric study of foramen ovale.
To note the morphological variations and morphometric details of foramina ovale in dry adult skulls of Indian origin. 82 dry adult human skulls of unknown sex and of Indian origin were obtained and variations in appearance and number of foramen ovale were noted. The length and width of the foramina ovale of both sides were determined using digital Vernier calipers and area (A) was also calculated and analyzed. Out of 82 adult skulls, the values for the right side was 7.64 ± 1.194 mm, 5.128 ± 0.827 mm and 30.808 ± 7.545 mm2 and for the left side the values was 7.561 ± 1.123 mm, 5.244 ± 0.950 mm and 31.310 ± 8.262 mm2 respectively, for the mean length, width and area of the foramen ovale. The shape of foramen was typically ovale in most of the skulls (56.70%) with some bony variations such as spine, tubercles etc. There was no statistically significant difference between the two sides in length, width and area of foramen ovale and there was a positive correlation between lengths and areas of both sides.


Spatial Soundscapes and Virtual Worlds: Challenges and Opportunities.
There is increasing effort to characterize the soundscapes around us so that we can design more compelling and immersive experiences. This review paper focuses on the challenges and opportunities around sound perception, with a particular focus on spatial sound perception in a virtual reality (VR) cityscape. We review how research on temporal aspects has recently been extended to evaluating spatial factors when designing soundscapes. In particular, we discuss key findings on the human capability of localizing and distinguishing spatial sound cues for different technical setups. We highlight studies carried out in both real-world and virtual reality settings to evaluate spatial sound perception. We conclude this review by highlighting the opportunities offered by VR technology and the remaining open questions for virtual soundscape designers, especially with the advances in spatial sound stimulation.


Sexual behaviour, knowledge and awareness of related reproductive health issues among single youth in Ethiopia.
This nationally representative study, encompassing all single youth (15-24 years), was carried out on the subpopulation of Ethiopia DHS 2000 to determine the influences of socio-demographic characteristics on sexual behaviour, and assess the knowledge and awareness of HIV/AIDS and other STIs. There were a total of 890 male and 3,988 female youth. 25.5% of males and 16.1% of females ever had sexual intercourse. Among these, 65.8% males and 24.6% females had two or more sexual partners in the last 12 months. Condom use in the last sexual act was reported by 22.7% and 10% of male and female youth. 19.4% of male and 22.2% of female youth who ever had sexual intercourse ever used family planning method. Although the majority of youth is aware of HIV/AIDS, awareness about other STIs is low. On binary logistic regression analysis, the odds of ever having sexual intercourse were higher for the employed and older youth. Male urban youth was more likely to ever have sexual intercourse than male rural youth (Adjusted OR 4.2; 95% CI 1.8-9.5). Male youth with some form of education were more likely to use condom (Adjusted OR 4.9; 95% CI 1.01-24.7). Female youth with some form of education, the risk of ever having sexual intercourse was reduced by 50% but they were more likely to report having 2 sexual partners in the last 12 months (Adjusted OR 2.1; 95% CI 1.1-4.1). Female youth who had media exposure were more likely to report having 2 sexual partners in the last 12 months (Adjusted OR 2.9; 95% CI 1.3-6.8) but more likely to use condom during last sexual intercourse (Adjusted OR 15.7; 95% CI2.2-117). Among single Ethiopian youth the overall sexual activity is relatively lower than reported from other African countries but high risk sexual behaviour is common. Socio-demographic factors influence youth sexual behaviour.


Establishment of Monoclonal Antibody Standards for Quantitative Serological Diagnosis of SARS-CoV-2 in Low-Incidence Settings.
Serological confirmation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for understanding the dynamics of the pandemic and determining seroprevalence rates within afflicted communities. Common challenges with SARS-CoV-2 serological assays include poor analytical specificity and sensitivity and lack of a serological standard for quantitative assessment of antibody titers. To overcome these obstacles, we developed a quantitative enzyme-linked immunosorbent assay based on an optimized 2-dimensional screening assay that utilizes SARS-CoV-2 receptor binding domain (RBD) of spike protein and SARS-CoV-2 spike S1 subunit. A total of 4 SARS-CoV-2-reactive monoclonal antibodies were evaluated for use as serum standards for calibrating assays performed on different days or by different laboratories. This approach provided quantitative analysis of hospitalized reverse transcription polymerase chain reaction-confirmed COVID-19 cases that in some cases reached >100 μg/mL. The assay demonstrated 72% sensitivity based on time points ranging from 2 to 52 days post-symptom onset, with 100% sensitivity at time points measured ≥13 days post-symptom onset and 100% specificity. Using these optimized reagents and serological standards, we believe this approach will be useful for sensitive and specific determination of seroconversion rates and quantitatively measuring the durability of antiviral antibody responses following SARS-CoV-2 infection or vaccination.


Role of nociceptin/orphanin FQ in age-dependent cerebral hemodynamic effects of brain injury.
This study was designed to compare the role of the newly described endogenous opioid nociceptin/orphanin FQ (NOC/oFQ) in the reductions of cerebral blood flow (CBF) and pial artery diameter observed following fluid percussion brain injury (FPI) in chloralose anesthetized newborn and juvenile pigs as a function of time postinsult. FPI elevated CSF NOC/oFQ concentration from 70 +/- 3 to 444 +/- 51 within 1 h and to 1,931 +/- 112 pg/mL (n = 7) within 8 h, whereas concentrations returned to control value within 168 h in the newborn. In contrast, FPI elevated CSF NOC/oFQ from 77 +/- 4 to 202 +/- 16 pg/mL (n = 7) within 1 h, while values returned to control value within 8 h in the juvenile. Topical NOC/oFQ (10(-8), 10(-6) M) induced vasodilation was reversed to vasoconstriction by FPI in the newborn while such responses were only attenuated in the juvenile at 1 h post insult (control, 9 +/- 1 and 16 +/- 1%; FPI newborn, -8 +/- 1 and -14 +/- 1%; FPI juvenile, 2 +/- 1 and 5 +/- 1%, n = 7). Such altered dilation returned to control value within 168 h in newborns and 8 h in juveniles. Blood flow in the cerebrum was reduced from 57 +/- 4 to 23 +/- 3 mL x min(-1) x 100 g(-1) (n = 7) within 1 h and returned to control value with 168 h post FPI in newborns. In animals pretreated with [F/G] NOC/oFQ (1-13) NH2 (1 mg/kg, i.v.), a NOC/oFQ antagonist, however, CBF only fell to 39 +/- 4 mL x min(-1) x 100 g(-1) (n = 7) at 1 h post insult in newborns. In contrast, CBF was only reduced from 57 +/- 6 to 32 +/- 2 in untreated and to 39 +/- 3 mL/min(-1) x 100 g(-1) (n = 7) in treated juveniles within 1 h post FPI. Similar observations for reductions in pial artery diameter were made in untreated and treated newborns and juveniles. These data suggest that an elevated CSF NOC/oFQ concentration and altered vascular responsiveness to this opioid contribute to reductions in CBF and pial artery diameter observed following FPI. Because such NOC/oFQ changes were greater in newborns versus juveniles, these data further suggest that NOC/oFQ contributes to age-related cerebral hemodynamic differences in the effects of FPI.


[Prophylaxis of hypoparathyroidism after operations on the thyroid gland].
An analysis of results of surgical treatment of 50 patients aged from 16 to 75 years with different diseases of the thyroid has shown that the frequency of decrease of the level of calcium and parathormone becomes less in the row: diffuse toxic goiter, cancer of the thyroid gland, polynodous euthyroid goiter. Decrease of the calcium and parathormone level is associated with deterioration of blood circulation and functional activity of parathyroid glands after operation on the thyroid gland. The patients after operation on the thyroid gland need prophylactic administration of calcium preparations.


[Investigation of reduction of exposure dose in digital mammography: relationship between exposure dose and image processing].
In digital mammograms, granularity is an important image property for the detection of microcalcifications and masses. Therefore, we investigated the relationship between the conditions of various exposure doses and the detectability of RMI156 phantom images with and without image processing for the reduction of exposure dose. The images are processed with Gaussian filter and unsharp-masking filters to evaluate the effects on image properties by using the digital Wiener spectrum (WS) presampled modulation transfer function (MTF). In addition, observer performance tests for the detectability of microcalcifications and masses are performed. With Gaussian filtering, the WS value decreased to 50% at 2.0 cycles/mm and the detectability score of masses increased 80% and 12%, on 1.34 mGy and 2.62 mGy, respectively (p<0.05). With unsharp-masking (7 x 7 pixels), the MTF value increased to 126% at 2.0 cycles/mm, and the detectability of microcalcification to 32% and 5%, on 1.34 mGy and 5.28 mGy, respectively (p<0.05) compared with the original image. The optimal dose of simulated lesions with unsharp masking became 5.25 mGy. The unsharp masking could reduce 37% of the exposure dose without a loss of detectability of microcalcifications and masses.


Accelerating language emergence by functional pressures.
In language emergence, neural agents acquire communication skills by interacting with one another and the environment. Through these interactions, agents learn to connect or ground their observations to the messages they utter, forming a shared consensus about the meaning of the messages. Such connections form what we refer to as a grounding map. However, these maps can often be complicated, unstructured, and contain redundant connections. In this paper, we introduce two novel functional pressures, modeled as differentiable auxiliary losses, to simplify and structure the grounding maps. The first pressure enforces compositionality via topological similarity, which has been previously discussed but has not been modeled or utilized as a differentiable auxiliary loss. The second functional pressure, which is conceptually novel, imposes sparsity in the grounding map by pruning weaker connections while strengthening the stronger ones. We conduct experiments in multiple value-attribute environments with varying communication channels. Our methods achieve improved out-of-domain regularization and rapid convergence over baseline approaches. Furthermore, introduced functional pressures are robust to the changes in experimental conditions and able to operate with minimum training data. We note that functional pressures cause simpler and more structured emergent languages showing distinct characteristics depending on the functional pressure employed. Enhancing grounding map sparsity yields the best performance and the languages with the most compressible grammar. In summary, our novel functional pressures, focusing on compositionality and sparse groundings, expedite the development of simpler, more structured languages while enhancing their generalization capabilities. Exploring alternative types of functional pressures and combining them in agent training may be beneficial in the ongoing quest for improved emergent languages.