Word learning deficit among Chinese dyslexic children.
The present study examined word learning difficulties in Chinese dyslexic children, readers of a nonalphabetic script. A total of 105 Hong Kong Chinese children were recruited and divided into three groups: Dyslexic (mean age 8;8), CA control (mean age 8;9), and RL control (mean age 6; 11). They were given a word learning task and a familiar word writing task. It was found that the Dyslexic group performed less well than the RL group in learning irregular words over trials but not the regular ones. Error analyses showed that the Dyslexic group made more orthographic and word association errors but less intra-wordlist interference errors than the RL control group. The Dyslexic group also performed significantly less well than both control groups in writing familiar words (e.g. their own name). These findings suggest that Chinese dyslexic children have difficulty learning new words, especially irregular ones, and retaining overlearned words in long-term memory. We conclude that Chinese dyslexic children have a specific impairment in word learning like their alphabetic counterparts.


Planning the transition of children with complex needs from hospital to home.
Planning and facilitating a high quality transition from hospital to home for children and young people with complex health needs is an important part of enabling them, and their families, to enjoy a good quality of life. This includes: identifying their health, social and education needs; what aspects of these needs their family can meet and what they will need assistance with; who should be involved in supporting them; the practicalities of what support and assistance they will need; how the funding required to meet their needs will be organised; and how their needs can be met in the context of their whole family.


Heavy Particle Impact Vibrational Excitation and Dissociation Processes in CO2.
A heavy particle impact vibrational excitation and dissociation model for CO2 is presented. This state-to-state model is based on the forced harmonic oscillator (FHO) theory, which is more accurate than current state-of-the-art kinetic models of CO2 based on first-order perturbation theory. The first excited triplet state 3B2 of CO2, including its vibrational structure, is considered in our model, and a more consistent approach to CO2 dissociation is also proposed. The model is benchmarked against a few academic zero-dimensional (0D) cases and compared to decomposition time measurements in a shock tube. Our model is shown to have reasonable predictive capabilities, and the CO2 + O ↔ CO + O2 reaction is found to have a key influence on the dissociation dynamics of CO2 shocked flows, warranting further theoretical studies. We conclude this study with a discussion on the theoretical improvements that are still required for a more consistent analysis of the vibrational/dissociation dynamics of CO2.


[Giant dedifferenciated liposarcoma of the spermatic cord].
To describe a patient with dedifferentiated liposarcoma of the spermatic cord and to perform a bibliographic review. We describe the case of a patient with dedifferentiated liposarcoma of the spermatic cord, and conducted an extensive search of literature in different databases that support the discussion of the case. A 65 years old male presented a right scrotal mass with progressive growth, and underwent excision of the mass (measured 34 x 22 x 17 cm and weighed 5786 grams). Pathology reported dedifferentiated liposarcoma of the spermatic cord. This patient draws attention to the reoccurrence of papillary thyroid cancer. Paratesticular tumors are rare entities, derived from mesenchymal tissue. Most of them are benign, but up to 30% could be of sarcomatoid type. Their treatment is based on the extraction of the mass along with radical orchiectomy, but being a very rare disease is not clear whether the benefit of adjuvant chemotherapy and radiotherapy in these patients is beneficial.


Evaluation of methods to sample fecal indicator bacteria in foreshore sand and pore water at freshwater beaches.
Fecal indicator bacteria (FIB) are known to accumulate in foreshore beach sand and pore water (referred to as foreshore reservoir) where they act as a non-point source for contaminating adjacent surface waters. While guidelines exist for sampling surface waters at recreational beaches, there is no widely-accepted method to collect sand/sediment or pore water samples for FIB enumeration. The effect of different sampling strategies in quantifying the abundance of FIB in the foreshore reservoir is unclear. Sampling was conducted at six freshwater beaches with different sand types to evaluate sampling methods for characterizing the abundance of E. coli in the foreshore reservoir as well as the partitioning of E. coli between different components in the foreshore reservoir (pore water, saturated sand, unsaturated sand). Methods were evaluated for collection of pore water (drive point, shovel, and careful excavation), unsaturated sand (top 1 cm, top 5 cm), and saturated sand (sediment core, shovel, and careful excavation). Ankle-depth surface water samples were also collected for comparison. Pore water sampled with a shovel resulted in the highest observed E. coli concentrations (only statistically significant at fine sand beaches) and lowest variability compared to other sampling methods. Collection of the top 1 cm of unsaturated sand resulted in higher and more variable concentrations than the top 5 cm of sand. There were no statistical differences in E. coli concentrations when using different methods to sample the saturated sand. Overall, the unsaturated sand had the highest amount of E. coli when compared to saturated sand and pore water (considered on a bulk volumetric basis). The findings presented will help determine the appropriate sampling strategy for characterizing FIB abundance in the foreshore reservoir as a means of predicting its potential impact on nearshore surface water quality and public health risk.


Critical care in the austere environment: providing exceptional care in unusual places.
War and other disasters are inexorably linked to illness and injury. As a consequence of this, healthcare providers will be challenged to provide advanced physiological support to preserve human life. Given the mobility and modularity of modern medical systems, the ability to provide critical care outside of the confines of traditional hospitals under such circumstances has become not only a reality and periodic necessity, but an expectation. Austerity amplifies the complexity of providing high-level critical care, because resources are frequently limited, providers are asked to fill unexpected roles determined by necessity, security may be threatened, and the population at risk and their afflictions can be highly diverse. Our current deployed military medical experience and a review of published literature pertaining to civilian medical disaster response efforts support these stated challenges. The fundamentals of successful critical care practice in unusual settings include proper planning with an emphasis on attention to detail, the careful management of all resources, using the proper equipment, leveraging aeromedical evacuation assets, and employing the right people with the right skills. Adherence to sound, evidence-based, routine practice, within bounds of the circumstances, must underscore everything.


The p. N103K mutation of leptin (LEP) gene and severe early onset obesity in Pakistan.
Obesity is a complex disorder and has been increasing globally at alarming rates including Pakistan. However, there is scarce research on understanding obesity genetics in Pakistan. Leptin is a hormone secreted by adipocytes in response to satiety and correlates with body weight. Any mutations in the LEP gene have an adverse effect on energy regulation pathway and lead to severe, early onset obesity. To date, only eight mutations have been described in the LEP gene of which p. N103K is one. We aimed to analyze the prevalence of this mutation in Pakistani subjects. A total of 475 subjects were genotyped by PCR-RFLP analysis and their serum profiling was done. Results showed that this mutation was present only in one male child with early onset obesity (10 year). He had very low serum leptin levels suggestive of functional impact of the mutation. The prevalence of such mutations is, however, low due to the drastic effects on the energy regulation. In conclusion, LEP gene mutations contribute significantly to the monogenic forms of obesity and are important due to the availability of treatment options. Such mutations may exert their effect by directly affecting energy regulation pathway and are more prominent in the early stages of life only.


Bayesian Inference of Allele-Specific Gene Expression Indicates Abundant Cis-Regulatory Variation in Natural Flycatcher Populations.
Polymorphism in cis-regulatory sequences can lead to different levels of expression for the two alleles of a gene, providing a starting point for the evolution of gene expression. Little is known about the genome-wide abundance of genetic variation in gene regulation in natural populations but analysis of allele-specific expression (ASE) provides a means for investigating such variation. We performed RNA-seq of multiple tissues from population samples of two closely related flycatcher species and developed a Bayesian algorithm that maximizes data usage by borrowing information from the whole data set and combines several SNPs per transcript to detect ASE. Of 2,576 transcripts analyzed in collared flycatcher, ASE was detected in 185 (7.2%) and a similar frequency was seen in the pied flycatcher. Transcripts with statistically significant ASE commonly showed the major allele in >90% of the reads, reflecting that power was highest when expression was heavily biased toward one of the alleles. This would suggest that the observed frequencies of ASE likely are underestimates. The proportion of ASE transcripts varied among tissues, being lowest in testis and highest in muscle. Individuals often showed ASE of particular transcripts in more than one tissue (73.4%), consistent with a genetic basis for regulation of gene expression. The results suggest that genetic variation in regulatory sequences commonly affects gene expression in natural populations and that it provides a seedbed for phenotypic evolution via divergence in gene expression.


Unveiled electric profiles within hydrogen bonds suggest DNA base pairs with similar bond strengths.
Electrical forces are the background of all the interactions occurring in biochemical systems. From here and by using a combination of ab-initio and ad-hoc models, we introduce the first description of electric field profiles with intrabond resolution to support a characterization of single bond forces attending to its electrical origin. This fundamental issue has eluded a physical description so far. Our method is applied to describe hydrogen bonds (HB) in DNA base pairs. Numerical results reveal that base pairs in DNA could be equivalent considering HB strength contributions, which challenges previous interpretations of thermodynamic properties of DNA based on the assumption that Adenine/Thymine pairs are weaker than Guanine/Cytosine pairs due to the sole difference in the number of HB. Thus, our methodology provides solid foundations to support the development of extended models intended to go deeper into the molecular mechanisms of DNA functioning.


Augmentation in depression: Esketamine, a new standard?
While new add-on treatments have been developed for augmentation in depression with benefits demonstrated compared to placebo, none have demonstrated superiority compared to previously available interventions until now. In a phase IIIb, randomized, active-controlled trial (ESCAPE-TRD), Reif et al.1 demonstrate the superiority of esketamine compared to quetiapine augmentation (the current standard-of-care).


Conductive carbon tape used for support and mounting of both whole animal and fragile heat-treated tissue sections for MALDI MS imaging and quantitation.
Analysis of whole animal tissue sections by MALDI MS imaging (MSI) requires effective sample collection and transfer methods to allow the highest quality of in situ analysis of small or hard to dissect tissues. We report on the use of double-sided adhesive conductive carbon tape during whole adult rat tissue sectioning of carboxymethyl cellulose (CMC) embedded animals, with samples mounted onto large format conductive glass and conductive plastic MALDI targets, enabling MSI analysis to be performed on both TOF and FT-ICR MALDI mass spectrometers. We show that mounting does not unduly affect small molecule MSI detection by analyzing tiotropium abundance and distribution in rat lung tissues, with direct on-tissue quantitation achieved. Significantly, we use the adhesive tape to provide support to embedded delicate heat-stabilized tissues, enabling sectioning and mounting to be performed that maintained tissue integrity on samples that had previously been impossible to adequately prepare section for MSI analysis. The mapping of larger peptidomic molecules was not hindered by tape mounting samples and we demonstrate this by mapping the distribution of PEP-19 in both native and heat-stabilized rat brains. Furthermore, we show that without heat stabilization PEP-19 degradation fragments can detected and identified directly by MALDI MSI analysis.


Emergency drug kits at the Danish hospital pharmacies: varying management and challenges.
Access to emergency drug kits (EDK) during medical emergencies can be life-saving; however, recent doubts about the quality of the kits have been expressed. Procurements of pharmaceuticals to the five regional authorities in Denmark are serviced by Amgros, a public sector organisation owned by the regions and established to create economies of scale and achieve administrative savings by centralisation. This means that Amgros calls for tenders for the supply of pharmaceuticals to the hospital pharmacies. The Hospital Pharmacy in the North Denmark Region does not currently have an effective method to manage Amgros procurements in relation to EDKs. Thus, the objectives were to explore how quality in the management and packing of EDKs is assured and maintained at different hospital pharmacies in Denmark and how this is affected by Amgros procurements. The hospital pharmacies in Denmark were enrolled in a cross-sectional study. Information about the management and challenges of the EDKs was inquired by means of a questionnaire. Responses were analysed by simple statistics. All eight hospital pharmacies in Denmark completed the questionnaire, and the distribution between single-use and reusable packaging was nearly equal. The hospital pharmacies comply with a variation of regulations of which good distribution practice is the most common. Six hospital pharmacies experience challenges with drug replacements in the EDKs and only one hospital pharmacy complies completely with the Amgros procurement. The majority of the hospital pharmacies use parameters such as price of the new drug and potential expense for new packaging in their decision of whether to comply with the Amgros procurement. The management of the EDKs varies greatly among the hospital pharmacies in Denmark, and national requirements are therefore encouraged to ensure the quality. The challenges experienced with drug replacements reflect that complying with the Amgros procurement can be troublesome.


Verification of an alternative sludge treatment process for pathogen reduction at two wastewater treatment plants in Victoria, Australia.
At South East Water wastewater treatment plants (WwTPs) in Victoria, Australia, biosolids are stockpiled for three years in compliance with the State guidelines to achieve the highest pathogen reduction grade (T1), suitable for unrestricted use in agriculture and landscaping. However, extended stockpiling is costly, may increase odour nuisance and greenhouse gas emissions, and reduces the fertiliser value of the biosolids. A verification programme of sampling and analysis for enteric pathogens was conducted at two WwTPs where sludge is treated by aerobic and anaerobic digestion, air drying (in drying pans or solar drying sheds) and stockpiling, to enumerate and, if present, monitor the decay of a range of enteric pathogens and parasites. The sludge treatment processes at both WwTPs achieved T1 grade biosolids with respect to prescribed pathogenic bacterial numbers (<1 Salmonella spp. 50 g-1 dry solids (DS) and <100 Escherichia coli g-1 DS) and >3 log10 enteric virus reduction after a storage period of one year. No Ascaris eggs were detected in the influent to the WwTPs, confirming previous studies that the presence of helminth infections in Victoria is extremely low and that Ascaris is not applicable as a control criterion for the microbiological quality of biosolids in the region.


Amine functionalised silicon nanocrystals with bright red and long-lived emission.
When functionalised with amines, silicon nanocrystals (SiNCs) are known to have surface-state emission with loss of colour tunability, low quantum yield and short nanosecond lifetimes. These changes in optical properties are produced by direct amine bonding on the silicon surface. In this article, secondary amine functionalised SiNCs with bright, red (λmax = 750 nm) and long-lived emission (τ ca. 50 μs) are reported for the first time via a three-step synthetic approach. These SiNCs are colloidally stable in several polar solvents and can be further functionalised by reaction with carboxylic acid groups. We proved the feasibility of further functionalization with pyrene butyric acid: ca. 40 pyrene units per nanoparticle were attached via amide bond formation. The resulting hybrid system works as a light-harvesting antenna: excitation of pyrene units at 345 nm results in sensitised emission at 700 nm by the silicon core.


Spike-based population coding and working memory.
Compelling behavioral evidence suggests that humans can make optimal decisions despite the uncertainty inherent in perceptual or motor tasks. A key question in neuroscience is how populations of spiking neurons can implement such probabilistic computations. In this article, we develop a comprehensive framework for optimal, spike-based sensory integration and working memory in a dynamic environment. We propose that probability distributions are inferred spike-per-spike in recurrently connected networks of integrate-and-fire neurons. As a result, these networks can combine sensory cues optimally, track the state of a time-varying stimulus and memorize accumulated evidence over periods much longer than the time constant of single neurons. Importantly, we propose that population responses and persistent working memory states represent entire probability distributions and not only single stimulus values. These memories are reflected by sustained, asynchronous patterns of activity which make relevant information available to downstream neurons within their short time window of integration. Model neurons act as predictive encoders, only firing spikes which account for new information that has not yet been signaled. Thus, spike times signal deterministically a prediction error, contrary to rate codes in which spike times are considered to be random samples of an underlying firing rate. As a consequence of this coding scheme, a multitude of spike patterns can reliably encode the same information. This results in weakly correlated, Poisson-like spike trains that are sensitive to initial conditions but robust to even high levels of external neural noise. This spike train variability reproduces the one observed in cortical sensory spike trains, but cannot be equated to noise. On the contrary, it is a consequence of optimal spike-based inference. In contrast, we show that rate-based models perform poorly when implemented with stochastically spiking neurons.


The ribosome-bound quality control complex: from aberrant peptide clearance to proteostasis maintenance.
Proteostasis in eukaryotes is maintained by compartment-specific quality control pathways, which enable the refolding or the degradation of defective polypeptides to prevent the toxicity that may arise from their aggregation. Among these processes, translational protein quality control is performed by the Ribosome-bound Quality Control complex (RQC), which recognizes nascent peptides translated from aberrant mRNAs, polyubiquitylates these aberrant peptides, extracts them from the stalled 60S subunit and finally escorts them to the proteasome for degradation. In this review, we focus on the mechanism of action of the RQC complex from stalled 60S binding to aberrant peptide delivery to the proteasome and describe the cellular consequences of a deficiency in the RQC pathway, such as aberrant protein aggregation. In addition, this review covers the recent discoveries concerning the role of cytosolic chaperones, as well as Tom1, to prevent the accumulation of aberrant protein aggregates in case of a deficiency in the RQC pathway.


Pineal N-acetyltransferase is inactivated by disulfide-containing peptides: insulin is the most potent.
Pineal N-acetyltransferase can be inactivated in broken cell preparations by cystamine through a mechanism of thiol-disulfide exchange. Some, but not all, disulfide-containing peptides can inactivate this enzyme; the most potent inactivator is insulin. These findings suggest that a disulfide-containing peptide with high reactivity toward N-acetyltransferase may participate in the intracellular regulation of this enzyme.


Electrospun micro- and nanofibers for sustained delivery of paclitaxel to treat C6 glioma in vitro.
The present study aims to develop electrospun PLGA-based micro- and nanofibers as implants for the sustained delivery of anticancer drug to treat C6 glioma in vitro. PLGA and an anticancer drug--paclitaxel-loaded PLGA micro- and nanofibers were fabricated by electrospinning and the key processing parameters were investigated. The physical and chemical properties of the micro- and nanofibers were characterized by various state-of-the-art techniques, such as scanning electron microscope and field emission scanning electron microscope for morphology, X-ray photoelectron spectroscopy for surface chemistry, gel permeation chromatogram for molecular weight measurements and differential scanning calorimeter for drug physical status. The encapsulation efficiency and in vitro release profile were measured by high performance liquid chromatography. In addition, the cytotoxicity of paclitaxel-loaded PLGA nanofibers was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide MTT) assay on C6 glioma cell lines. PLGA fibers with diameters of around several tens nanometers to 10 microm were successfully obtained by electrospinning. Ultrafine fibers of around 30 nm were achieved after addition of organic salts to dilute polymer solution. The encapsulation efficiency for paclitaxel-loaded PLGA micro- and nanofibers was more than 90%. DSC results suggest that the drug was in the solid solution state in the polymeric micro- and nanofibers. In vitro release profiles suggest that paclitaxel sustained release was achieved for more than 60 days. Cytotoxicity test results suggest that IC50 value of paclitaxel-loaded PLGA nanofibers (36 microg/ml, calculated based on the amount of paclitaxel) is comparable to the commercial paclitaxel formulation-Taxol. Electrospun paclitaxel-loaded biodegradable micro- and nanofibers may be promising for the treatment of brain tumour as alternative drug delivery devices.


'A Home to the Lie': The Contemporary (Per)version of Truth.
This paper explores the contemporary trend towards relativization and perversion of truth increasingly prominent in American culture, which, in Bion's terminology (1970), has become an ever more hospitable "home to the lie." The anti-COVID vaccine movement emerging in the United States in 2021, and its related network of conspiracy theories, is presented as an example. To make sense of these phenomena the author presents clinical vignettes illustrating (1) Bion's (1970) notions of catastrophic change, the lie/thinker relation, and the messianic idea; (2) Freud's (1921) thinking on group leaders; and (3) Matte-Blanco's (1975) bi-logical theory of mind. According to Bion, the lie is mobilized to avoid the psychological upheaval associated with catastrophic change. The author suggests that developments in American life experienced as threatening catastrophic change provide a hospitable environment for the lie, making the recognition of truth more elusive. In line with Matte-Blanco's bi-logical theory, the author suggests that creation of opportunities for dialogue giving weight to both conscious and unconscious ways of thinking is necessary for re-establishing a culture of truth.


A sodium zinc exchange mechanism is mediating extrusion of zinc in mammalian cells.
Zinc influx, driven by a steep inward electrochemical gradient, plays a fundamental role in zinc signaling and in pathophysiologies linked to intracellular accumulation of toxic zinc. Yet, the cellular transport mechanisms that actively generate or maintain the transmembrane gradients are not well understood. We monitored Na+-dependent Zn2+ transport in HEK293 cells and cortical neurons, using fluorescent imaging. Treatment of the HEK293 cells with CaPO4 precipitates induced Na+-dependent Zn2+ extrusion, against a 500-fold transmembrane zinc gradient, or zinc influx upon reversal of Na+ gradient, thus indicating that Na+/Zn2+ exchange is catalyzing active Zn2+ transport. Depletion of intracellular ATP did not inhibit the Na+-dependent Zn2+ extrusion, consistent with a mechanism involving a secondary active transporter. Inhibitors of the Na+/Ca2+ exchanger failed to inhibit Na+-dependent Zn2+ efflux. In addition, zinc transport was unchanged in HEK293 cells heterologously expressing functional cardiac or neuronal Na+/Ca2+ exchangers, thus indicating that the Na+/Zn2+ exchange activity is not mediated by the Na+/Ca2+ exchanger. Sodium-dependent zinc exchange, facilitating the removal of intracellular zinc, was also monitored in neurons. To our knowledge, the Na+/Zn2+ exchanger described here is the first example of a mammalian transport mechanism capable of Na+-dependent active extrusion of zinc. Such mechanism is likely to play an important role, not only in generating the transmembrane zinc gradients, but also in protecting cells from the potentially toxic effects of permeation of this ion.


Environmental photochemistry of tylosin: efficient, reversible photoisomerization to a less-active isomer, followed by photolysis.
The environmental photochemical kinetics of tylosin, a common veterinary macrolide antibiotic and growth promoter, were investigated under simulated sunlight. An efficient, reversible photoisomerization was characterized using kinetic, mass spectrometry, and proton nuclear magnetic resonance data. The photoisomerization was confirmed to occur by a rotation about the distal alkene of the ketodiene functionality. Concurrent forward (quantum yield = 0.39 +/- 0.09) and back (quantum yield = 0.32 +/- 0.08) reactions lead to a photochemical equilibrium near a tylosin/photoisomer ratio of 50:50, completed in less than 2 min under a spectrum equivalent to noontime, summer sunlight. The activity of the isomer for the inhibition of Escherichia coli DH5alpha growth was observed to be less than that of tylosin. On a longer time scale than that of isomerization, the isomer mixture undergoes photolysis with a quantum yield of (1.4 +/- 0.3) x 10(-3). The observed quantum yields and UV-vis absorbance data allow for the prediction of the photochemical behavior of tylosin in most environmental systems. Indirect photosensitization was not a significant loss process in solutions of Suwannee River fulvic acid with concentrations from 1 to 20 mg L(-1).


Implantation depth of balloon-expandable transcatheter heart valves and risks for permanent pacemaker implantation and midterm adverse events.
Permanent pacemaker implantation (PPI) remains a relevant complication after transcatheter aortic valve implantation (TAVI) and its impact on outcome remains controversial. This study aimed to analyze the effects of implantation depth on PPI at 30 days and assess its impact on outcome with the balloon-expandable Sapien 3 (S3) prosthesis. Between 2014 and 2018, 849 patients without previous pacemaker undergoing transfemoral TAVI with the S3 were included. Prosthesis implantation depth was measured and divided into Quintiles. An ordinal logistic regression was used to assess its association with PPI, while a multivariate logistic regression was performed to identify predictors of PPI. Survival analyses were performed with the Kaplan-Meier method and a multivariable Cox regression was performed to ascertain the impact of PPI on mortality. Overall, incidence of PPI at 30 days was 9.7%. Implantation depth decreased consistently from a median of 6.7 mm [5.55-8.00] in 2014 to 2.7 mm [2.30-3.50] in 2018 (p < 0.001). When considering Quintiles of implantation depth, incidence of PPI was significantly higher in upper Quintiles and risk for PPI was significantly lower for the 1. Quintile compared to the 5. Quintile (OR: 0.34, 95% CI: [0.16-0.73]; p = 0.003). In the adjusted multivariable logistic regression implantation depth persisted ad independent predictor of PPI at 30 days. Patients requiring PPI at 30 days displayed significantly higher mortality at 4 years compared to patients without PPI (49.5% vs. 40.0%; log-rank = 0.022). In a multivariate analysis, increased logistic EuroScore, diabetes mellitus, and history of atrial fibrillation, were independent predictors of all-cause mortality at 2 years. Higher prosthesis implantation relative to the virtual aortic annulus was significantly associated with reduced risk for PPI at 30 days. Patients with PPI at 30 days exhibited higher mortality during follow-up, however, only logistic EuroScore, diabetes mellitus, and history of atrial fibrillation were identified as independent predictors of mortality at 2 years.


The Dynamics of Deformed Wing Virus Concentration and Host Defensive Gene Expression after Varroa Mite Parasitism in Honey Bees, Apis mellifera.
The synergistic interactions between the ectoparasitic mite Varroa destructor and Deformed wing virus (DWV) lead to the reduction in lifespan of the European honey bee Apis mellifera and often have been implicated in colony losses worldwide. However, to date, the underlying processes and mechanisms that form the multipartite interaction between the bee, mite, and virus have not been fully explained. To gain a better understanding of honey bees' defense response to Varroa mite infestation and DWV infection, the DWV titers and transcription profiles of genes originating from RNAi, immunity, wound response, and homeostatic signaling pathways were monitored over a period of eight days. With respect to DWV, we observed low viral titers at early timepoints that coincided with high levels of Toll pathway transcription factor Dorsal, and its downstream immune effector molecules Hymenoptaecin, Apidaecin, Abaecin, and Defensin 1. However, we observed a striking increase in viral titers beginning after two days that coincided with a decrease in Dorsal levels and its corresponding immune effector molecules, and the small ubiquitin-like modifier (SUMO) ligase repressor of Dorsal, PIAS3. We observed a similar expression pattern for genes expressing transcripts for the RNA interference (Dicer/Argonaute), wound/homeostatic (Janus Kinase), and tissue growth (Map kinase/Wnt) pathways. Our results demonstrate that on a whole, honey bees are able to mount an immediate, albeit, temporally limited, immune and homeostatic response to Varroa and DWV infections, after which downregulation of these pathways leaves the bee vulnerable to expansive viral replication. The critical insights into the defense response upon Varroa and DWV challenges generated in this study may serve as a solid base for future research on the development of effective and efficient disease management strategies in honey bees.


Enantioselective Diels-Alder reactions with N-hydroxy-N-phenylacrylamide.
[reaction: see text] The use of hydroxamic acids as templates for Lewis acid catalyzed enantioselective Diels-Alder reactions has been examined. A very simple chiral Lewis acid, prepared by mixing optically pure binaphthol with 3 equiv of trimethylaluminum, catalyzes the [4 + 2] cycloaddition of N-hydroxy-N-phenylacrylamide with cyclopentadiene at 0 degrees C in high yield (>96%) and with a fairly good level of enantioselectivity (91% ee). Facile conversion of the products to the corresponding alcohols or aldehydes makes the hydroxamic acid intermediates particularly useful.


[Mechanisms regulating the macrorheologic properties of the blood].
Macro-rheological features of human blood (the limit of fluidity, seeming viscosity in low shift velocities), cohesion power among erythrocytes, and hematocrit in pregnancy (36-38 weeks), in neonatal period, in acute and chronic heart disease, and in dogs with experimental hemorrhagic shock, were studied. Reduction of the cohesion power among erythrocytes was shown to occur in increase of hematocrit value. If the cohesion power increases it is followed by physiological hemodilution. The organism tries to prevent the increase of the macro-rheological parameters up to the level entailing irreversible disorders of microcirculation.


In Situ Representations and Access Consciousness in Neural Blackboard or Workspace Architectures.
Phenomenal theories of consciousness assert that consciousness is based on specific neural correlates in the brain, which can be separated from all cognitive functions we can perform. If so, the search for robot consciousness seems to be doomed. By contrast, theories of functional or access consciousness assert that consciousness can be studied only with forms of cognitive access, given by cognitive processes. Consequently, consciousness and cognitive access cannot be fully dissociated. Here, the global features of cognitive access of consciousness are discussed based on neural blackboard or (global) workspace architectures, combined with content addressable or "in situ" representations as found in the brain. These representations allow continuous cognitive access in the form of a process of covert or overt queries and answers that could underlie forms of access consciousness. A crucial aspect of this process is that it is controlled by the activity of the in situ representations themselves and the relations they can initiate, not by an external controller like a CPU that runs a particular program. Although the resulting process of access consciousness is indeed based on specific features of the brain, there are no principled reasons to assume that this process cannot be achieved in robots either.


Management of oral mucosal dysplasia with beta-carotene retinoic acid: a pilot cross-over study.
Mucosal dysplasia in the head and neck region is recognized to be a precancerous lesion. Between January 1983 and December 1987, a pilot study was conducted at the Manitoba Cancer Treatment and Research Foundation to determine the effects of beta-carotene and cis-retinoic acid on mucosal dysplasias. Eighteen patients were treated with a "cross-over" regimen. The overall response to treatment was 61%, with 33.3% complete responses. Patients who smoked had a significantly better response than nonsmokers. The response rate for 9 of 11 smokers was 81.2%, and 2 of 7 nonsmokers or 28.6% responded to this protocol. The beneficial effect of these drugs should be established by prospective, randomized trial in high risk populations.


[Effect of an increased content of oxygen and carbon dioxide on vestibular resistance].
Forty-two experiments on 21 test subjects, aged 20 to 40, were carried out to study possibilities of increasing vestibular resistance. This was achieved by improving the cerebral blood supply of the subjects who used the breathing air of 40-43% oxygen, 2% carbon dioxide and nitrogen. The results were treated statistically. This breathing air proved to increase the resistance of the vestibular analyzer to adequate stimuli. It is recommended to use this breathing air consisting of 40-43% oxygen, 2% carbon dioxide and nitrogen to prevent motion sickness and to discontinue vestibulo-vegetative disturbances that may appear in people using different flying and ground vehicles.


Media multitasking and implicit learning.
Media multitasking refers to the simultaneous use of different forms of media. Previous research comparing heavy media multitaskers and light media multitaskers suggests that heavy media multitaskers have a broader scope of attention. The present study explored whether these differences in attentional scope would lead to a greater degree of implicit learning for heavy media multitaskers. The study also examined whether media multitasking behaviour is associated with differences in visual working memory, and whether visual working memory differentially affects the ability to process contextual information. In addition to comparing extreme groups (heavy and light media multitaskers) the study included analysis of people who media multitask in moderation (intermediate media multitaskers). Ninety-four participants were divided into groups based on responses to the media use questionnaire, and completed the contextual cueing and n-back tasks. Results indicated that the speed at which implicit learning occurred was slower in heavy media multitaskers relative to both light and intermediate media multitaskers. There was no relationship between working memory performance and media multitasking group, and no relationship between working memory and implicit learning. There was also no evidence for superior performance of intermediate media multitaskers. A deficit in implicit learning observed in heavy media multitaskers is consistent with previous literature, which suggests that heavy media multitaskers perform more poorly than light media multitaskers in attentional tasks due to their wider attentional scope.


The Mental Health Parity and Addiction Equity Act Evaluation Study: Impact on Specialty Behavioral Health Care Utilization and Spending Among Carve-In Enrollees.
The federal Mental Health Parity and Addiction Equity Act (MHPAEA) sought to eliminate historical disparities between insurance coverage for behavioral health (BH) treatment and coverage for medical treatment. Our objective was to evaluate MHPAEA's impact on BH expenditures and utilization among "carve-in" enrollees. We received specialty BH insurance claims and eligibility data from Optum, sampling 5,987,776 adults enrolled in self-insured plans from large employers. An interrupted time series study design with segmented regression analysis estimated monthly time trends of per-member spending and use before (2008-2009), during (2010), and after (2011-2013) MHPAEA compliance (N=179,506,951 member-month observations). Outcomes included: total, plan, patient out-of-pocket spending; outpatient utilization (assessment/diagnostic evaluation visits, medication management, individual and family psychotherapy); intermediate care utilization (structured outpatient, day treatment, residential); and inpatient utilization. MHPAEA was associated with increases in monthly per-member total spending, plan spending, assessment/diagnostic evaluation visits [respective immediate increases of: $1.05 (P=0.02); $0.88 (P=0.04); 0.00045 visits (P=0.00)], and individual psychotherapy visits [immediate increase of 0.00578 visits (P=0.00) and additional increases of 0.00017 visits/mo (P=0.03)]. MHPAEA was associated with modest increases in total and plan spending and outpatient utilization; for example, in July 2012 predicted per-enrollee plan spending was $4.92 without MHPAEA and $6.14 with MHPAEA. Efforts should focus on understanding how other barriers to BH care unaddressed by MHPAEA may affect access/utilization. Future research should evaluate effects produced by the Affordable Care Act's inclusion of BH care as an essential health benefit and expansion of MHPAEA protections to the individual and small group markets.


Multi-omics characterization of molecular features of gastric cancer correlated with response to neoadjuvant chemotherapy.
Neoadjuvant chemotherapy is a common treatment for patients with gastric cancer. Although its benefits have been demonstrated, neoadjuvant chemotherapy is underutilized in gastric cancer management, because of the lack of biomarkers for patient selection and a limited understanding of resistance mechanisms. Here, we performed whole-genome, whole-exome, and RNA sequencing on 84 clinical samples (including matched pre- and posttreatment tumors) from 35 patients whose responses to neoadjuvant chemotherapy were rigorously defined. We observed increased microsatellite instability and mutation burden in nonresponse tumors. Through comparisons of response versus nonresponse tumors and pre- versus posttreatment samples, we found that C10orf71 mutations were associated with treatment resistance, which was supported by drug response data and potentially through inhibition of cell cycle, and that MYC amplification correlated with treatment sensitivity, whereas MDM2 amplification showed the opposite pattern. Neoadjuvant chemotherapy also reshapes tumor-immune signaling and microenvironment. Our study provides a critical basis for developing precision neoadjuvant regimens.


Challenges of applying the SHEA/HICPAC metrics for multidrug-resistant organisms to a real-world setting.
To test in a real-world setting the recommendations for measuring infection with multidrug-resistant organisms (MDRO) from the Society for Healthcare Epidemiology of America (SHEA) and the Centers for Disease Control and Prevention's Healthcare Infection Control Practices Advisory Committee (HICPAC). Using data from 3 hospital settings within a healthcare network, we applied the SHEA/HICPAC recommendations to measure methicillin-resistant Staphylococcus aureus (MRSA) infection and colonization. Data were obtained from the hospitals' electronic surveillance system and were supplemented by manual medical record review as necessary. Additionally, we tested (1) different definitions for nosocomial incidence, (2) the effect of excluding patients not at risk from the denominator for hospital-onset incidence, and (3) the appropriate time period to use when including or excluding patients with a prior history of MRSA infection or colonization from nosocomial rates. Negative binomial regression models were used to test for differences between rate definitions. A rating scale was created for each metric, assessing the extent to which manual or electronic data elements were required. There was no statistically significant difference between using 72 hours or 3 calendar days as the cutoff to define hospital-onset incidence. Excluding patients not at risk from the denominator when calculating hospital-onset incidence led to statistically significant increases in rates. When excluding patients with a prior history of MRSA infection or colonization from nosocomial incidence rates, rates were similar regardless of whether we looked at 1, 2, or 3 years' worth of prior data. The SHEA/HICPAC MDRO metrics are useful but can be challenging to implement. We include in our description of the data sources and processes required to calculate these metrics information that may simplify the process for institutions.


Influence of antipsychotic profile on cost of treatment of schizophrenia: A decision analysis approach.
Schizophrenia affects around 1% of the population but accounts for a much larger proportion of healthcare costs. New atypical antipsychotics are perceived as expensive because of higher drug costs, even though such drug costs account for only a small percentage of the total cost of care. However, if these agents reduce other types of treatment costs they could prove to be highly cost-effective. This paper presents a health economic model for the treatment of an acute episode of chronic schizophrenia and its subsequent control through maintenance treatment. Simulation experiments, using cost data reported for England, indicate that the most important treatment cost is care setting: treatments enabling patients to move from expensive inpatient and sheltered accommodation to less expensive settings represent the largest potential cost saving. Atypical antipsychotics with improved efficacy in negative symptoms and/or cognitive function may facilitate this and thus lead to substantial savings. Enhanced efficacy in positive symptoms, and improvements in compliance and relapse rates also have an influence on the cost of treating schizophrenia. Model predictions suggest that reported clinical profiles of atypical antipsychotics could lead to significant savings and large improvements in effectiveness over conventional therapy. Prospective studies are required to confirm these findings.


Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome.
DNA methylation is the most studied epigenetic mark and CpG methylation is central to many biological processes and human diseases. Since cancer has highlighted the contribution to disease of aberrant DNA methylation patterns, such as the presence of promoter CpG island hypermethylation-associated silencing of tumor suppressor genes and global DNA hypomethylation defects, their importance will surely become apparent in other pathologies. However, advances in obtaining comprehensive DNA methylomes are hampered by the high cost and time-consuming aspects of the single nucleotide methods currently available for whole genome DNA methylation analyses. Following the success of the standard CpG methylation microarrays for 1,505 CpG sites and 27,000 CpG sites, we have validated in vivo the newly developed 450,000 (450K) cytosine microarray (Illumina). The 450K microarray includes CpG and CNG sites, CpG islands/shores/shelves/open sea, non-coding RNA (microRNAs and long non-coding RNAs) and sites surrounding the transcription start sites (-200 bp to -1,500 bp, 5'-UTRs and exons 1) for coding genes, but also for the corresponding gene bodies and 3'-UTRs, in addition to intergenic regions derived from GWAS studies. Herein, we demonstrate that the 450K DNA methylation array can consistently and significantly detect CpG methylation changes in the HCT-116 colorectal cancer cell line in comparison with normal colon mucosa or HCT-116 cells with defective DNA methyltransferases (DKO). The provided validation highlights the potential use of the 450K DNA methylation microarray as a useful tool for ongoing and newly designed epigenome projects.


Thrombin stimulates tissue plasminogen activator release from cultured human endothelial cells.
The effect of thrombin on the release of tissue plasminogen activator from endothelial cells was studied in primary cultures of human umbilical vein endothelial cells. Tissue plasminogen activator concentration in conditioned medium was measured by a two-site radioimmunometric assay. The addition of increasing concentrations (0.01 to 10 U/ml) of thrombin to confluent cultures produced a saturable, dose-dependent increase in the rate of release of tissue plasminogen activator. A sixfold increase in tissue plasminogen activator concentration (from 2 to 12 ng/ml) occurred after the addition of 1 U/ml thrombin (8 X 10(-9) M) to cultures containing 5 X 10(4) cells/cm2. Enhanced release was not observed until 6 h after thrombin addition, reached a maximum rate of 1.3 ng/ml per h between 8 and 16 h, and then declined to 0.52 ng/ml per h after 16 h. The 6-h lag period before increased tPA release was reproducible and independent of thrombin concentration. Thrombin inactivated with diisopropylfluorophosphate or hirudin did not induce an increase in tissue plasminogen activator levels. A 50-fold excess of diisopropylfluorophosphate-treated thrombin, which inhibits binding of active thrombin to endothelial cell high affinity binding sites, did not inhibit the thrombin-induced increase. It is concluded that proteolitically active thrombin causes an increase in the rate of release of tissue plasminogen activator from cultured human endothelial cells. The 6-h interval between thrombin treatment and enhanced tissue plasminogen activator release may reflect a delaying mechanism that transiently protects hemostatic plugs from the sudden increase in the local concentration of this fibrinolytic enzyme.


Promising TMDC-like optical and excitonic properties of the TiBr2 2H monolayer.
The presented simulation protocol provides a solid foundation for exploring two-dimensional materials. Taking the TiBr2 2H monolayer as an example, this material displays promising TMDC-like optical and excitonic properties, making it an excellent candidate for optoelectronic and valleytronic applications. The direct band gap semiconductor (1.19 eV) is both structurally and thermodynamically stable, with spin-orbit coupling effects revealing a broken mirror symmetry in the K and K' valleys of the band structure, as confirmed by opposite values of the Berry curvature. A direct and bright exciton ground state was found, with an exciton binding energy of 0.56 eV. The study also revealed an optical helicity selection rule, suggesting selectivity in the valley excitation by specific circular light polarizations.


Development of schooling behaviour during the downstream migration of Atlantic salmon Salmo salar smolts in a chalk stream.
The downstream migratory behaviour of wild Atlantic salmon Salmo salar smolts was monitored using passive integrated transponder (PIT) antennae systems over 10 years in the lower reaches of a small chalk stream in southern England, U.K. The timing of smolt movements and the likely occurrence of schooling were investigated and compared to previous studies. In nine of the 10 consecutive years of study, the observed diel downstream patterns of S. salar smolt migration appeared to be synchronized with the onset of darkness. The distribution of time intervals between successive nocturnal detections of PIT-tagged smolts was as expected if generated randomly from observed hourly rates. There were, however, significantly more short intervals than expected for smolts detected migrating during the day. For each year from 2006 to 2011, the observed 10th percentile of the daytime intervals was <4 s, compared to ≥55 s for the simulated random times, indicating greater incidence of groups of smolts. Groups with the shortest time intervals between successive PIT tag detections originated from numerous parr tagging sites (used as a proxy for relatedness). The results suggest that the ecological drivers influencing daily smolt movements in the lower reaches of chalk stream catchments are similar to those previously reported at the onset of migration for smolts leaving their natal tributaries; that smolts detected migrating during the night are moving independently following initiation by a common environmental factor (presumably darkness), whereas those detected migrating during the day often move in groups, and that such schools may not be site (kin)-structured. The importance of understanding smolt migratory behaviour is considered with reference to stock monitoring programmes and enhancing downstream passage past barriers.


The impact of antenatal care on neonatal mortality in sub-Saharan Africa: A systematic review and meta-analysis.
Newborns are at greatest risk of dying at and shortly after the time of birth. Newborn mortality remains an urgent concern and is an important indicator of child health, development and well-being. Studies examining the effectiveness of antenatal care on maternal and newborn health outcomes have provided conflicting results. The aim of this review and meta-analysis was to determine the pooled effect of antenatal care on neonatal mortality in sub-Saharan Africa. We searched PubMed, Medline, EMBASE, CINAHL and Google Scholar from September to November 2016 and then updated our search on April 13, 2019. Two independent reviewers extracted data from eligible studies. The quality of each included study was assessed using the Risk of Bias Assessment tool for Non-Randomized Studies (RoBANS). The results were reported based on risk ratio (RR) with 95% confidence intervals (CI) using a random-effects model. Eight hundred and ninety eight studies were initially identified. During screening, 23 studies were found to be relevant for data extraction. Of these, only twelve studies fulfilled the inclusion criteria and were included in the analysis. In five of the twelve studies included in the analysis, antenatal care service utilization had a significant association with neonatal mortality. The pooled risk ratio by the random-effects model was 0.61 (95% CI: 0.43, 0.86) for neonates born to women who received at least one antenatal care visit by a skilled provider as compared to neonates born to women who did not receive antenatal care. This review indicates that utilization of at least one antenatal care visit by a skilled provider during pregnancy reduces the risk of neonatal mortality by 39% in sub-Saharan African countries. Thus, in order to accelerate progress towards the reduction of newborn deaths, all pregnant women should receive antenatal care during pregnancy.


[Increase in the number of repeating sequences of DNA in transcriptionally active sites of rat genome induced by cortisol and phenobarbital].
The effects of transcription inducers, e. g. cortisol, phenobarbital and 3-acetate-16 alpha (beta)-isothiocyano-pregnenolone (AIP), which, similar to phenobarbital, activates the multifunctional oxidase system, on the nucleotide sequence arrangement in the DNA fractions corresponding to functionally different sites of the genome, were investigated. Three DNA fractions were isolated from rat liver cells, using different concentrations of NaCl and different pH values of aqueous solutions of phenol used for deproteination. The DNA fraction I extracted with 1 M NaCl and phenol (pH 6.4) down to the water phase contains 12-14% of non-hydrolyzed by hybrid RNA RNAase, is rich in unique sequences, makes up to about 20% of the genome and probably corresponds to the transcriptionally active sites of chromatin DNA. The DNA fraction II extracted by 0.14 M NaCl and "alkaline" phenol (pH 8.5) makes up to 70% of total cellular DNA, in which the hybrid RNA content does not exceed 2%. The amount of weakly extractable and, possibly, membrane-bound DNA III does not exceed 10% of total DNA content. During induction of transcription the number of repeating sequences is increased by about 10% in DNA I and is simultaneously decreased in DNA III. This can both be due to the arrangement of sequences between chromatin fractions corresponding to membrane DNA and the transcriptionally active sites of the genome. Hybridization of [3H]rRNA demonstrated that the contribution of ribosomal genes to the above changes in the arrangement of sequences in DNA fractions under study is insignificant.


Effect of hyperbaric oxygen on certain growth features of Candida albicans.
Candida albicans (Robin) Berkhout, isolated from an adult female with recurring candidiasis, was tested in vitro for macroscopic and microscopic growth features at varying hyperbaric oxygen levels and at various exposure times and intervals. The organism was found to be inhibited within a pressure/time range well tolerated by human subjects, suggesting that hyperbaric oxygen might be used successfully in treating human candidiasis. Overall experimental results provide an in vitro basis for use of compression chamber therapy in candidiasis treatment.


Fate of Biodegradable Engineered Nanoparticles Used in Veterinary Medicine as Delivery Systems from a One Health Perspective.
The field of veterinary medicine needs new solutions to address the current challenges of antibiotic resistance and the need for increased animal production. In response, a multitude of delivery systems have been developed in the last 20 years in the form of engineered nanoparticles (ENPs), a subclass of which are polymeric, biodegradable ENPs, that are biocompatible and biodegradable (pbENPs). These platforms have been developed to deliver cargo, such as antibiotics, vaccines, and hormones, and in general, have been shown to be beneficial in many regards, particularly when comparing the efficacy of the delivered drugs to that of the conventional drug applications. However, the fate of pbENPs developed for veterinary applications is poorly understood. pbENPs undergo biotransformation as they are transferred from one ecosystem to another, and these transformations greatly affect their impact on health and the environment. This review addresses nanoparticle fate and impact on animals, the environment, and humans from a One Health perspective.


Identification and mutation analysis of DOC-1R, a DOC-1 growth suppressor-related gene.
The tumor suppressor gene MEN1 and several oncogenes including CCND1/cyclin D1/PRAD1 map to chromosome 11q13. However, molecular and cytogenetic analysis suggests the presence of a second tumor suppressor locus at this chromosome region. We have identified a novel gene from chromosome 11q13, which encodes a protein of 126 amino acids sharing an overall 57% identity with the p12(DOC-1) protein encoded by the DOC-1 gene, the human homolog of hamster putative tumor suppressor doc-1 (deleted in oral cancer-1). We therefore designated the novel gene as DOC-1R for DOC-1-related. The cytogenetic location was confirmed by chromosome fluorescent in situ hybridization. Northern blot analysis indicated that it was expressed in all the tissues examined. DOC-1R protein showed heterogeneous subcellular localization. RT-PCR-SSCP analysis failed to detect deleterious mutations of the DOC-1R transcript in four premalignant oral keratinocyte lines and 20 different cancer cell lines from tumor types which frequently harbor LOH at chromosome 11q13.


Ketogenic Diet in Alzheimer's Disease.
At present, the prevalence of Alzheimer's disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid β-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrial function, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer's disease. This review aims to examine the role of the ketogenic diet in Alzheimer's disease progression and to outline specific aspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer's disease.


Characterization of leukocyte subsets in buffalo (Bubalus bubalis) with cross-reactive monoclonal antibodies specific for bovine MHC class I and class II molecules and leukocyte differentiation molecules.
Although buffaloes (Bubalus bubalis) are a major component of the livestock industry worldwide, limited progress has been made in the study of the mechanisms regulating the immune response to pathogens and parasites affecting their health and productivity. This has been, in part, attributable to the limited availability of reagents to study immune responses in buffalo. As reported here, a set of cross-reactive monoclonal antibodies (mAbs), developed against bovine, ovine and caprine leukocyte differentiation molecules (LDM) and major histocompatibility complex (MHC) molecules, were identified and used to compare expression of LDM in Italian and Egyptian buffalo. The results show most of the epitopes identified with the mAbs are conserved on LDM and MHC I and II molecules in both lineages of buffalo. Comparison of the composition of lymphocyte subsets between buffalo and cattle revealed they are similar except for expression of CD2 and CD8 on workshop cluster one (WC1) positive γδ T cells. In cattle, CD8 is expressed on a subset of CD2+/WC1- γδ T cells that are present in low frequency in blood of young and old animals, whereas, CD8-/CD2-/WC1+ γδ T cells are present in high frequency in young animals, decreasing with age. In the buffalo, CD2 is expressed on a subset of WC1+ γδ T cells and CD8 is expressed on all WC1+ γδ T cells. The availability of this extensive set of mAbs provides opportunities to study the immunopathogenesis of pathogens and parasites affecting the health of buffalo.


Step-wise isolation of RNA and DNA from mycobacteria.
Mycobacterium phlei and M. smegmatis were lysed at -15 degrees C in the presence of guanidinium salts and poly(A)+-RNA. Nonpolyadenylated RNA (mainly rRNA) and DNA were isolated in successive steps from the same lysate. DNA isolated by this procedure was sufficient to yield distinct bands on treatment with restriction endonucleases as shown by hybridization to 125I-labeled rRNA. The successive isolation of poly(A)+-RNA, nonpolyadenylated RNA, and high molecular weight DNA from the same lysate by this procedure, which is being reported for the first time, provides a very economical approach for isolation and purification of nucleic acids from mycobacteria and other organisms. This could be of special value for various genetic recombination studies, particularly in the case of mycobacteria which are available in very limited quantities, e.g., noncultivable or difficult-to-grow mycobacteria, especially M. leprae.


Antiprismatic Coordination about Xenon: The Structure of Nitrosonium Octafluoroxenate(VI).
The structure of nitrosonium octafluoroxenate(VI), 2NOF . XeF(6), has been determined by means of single-crystal x-ray counter methods (R-index = 0.046, weighted R-index = 0.042). The space group is Pnma, with a = 8.914(10) angstroms, b = 5.945(10) angstroms, and c = 12.83(2) angstroms (the numbers in parentheses are the standard deviations to the least significant digit or digits); the calculated density (rho) is 3.354 grams per cubic centimeter, and there are four formula units per unit cell. The material consists of well-separated NO(+) and (XeF(8))(2-) ions; the structural formula is thus (NO)(2) (XeF(8)). The anion configuration is that of a slightly distorted Archimedean antiprism. The observed distortion appears incompatible with a lone-pair repulsion model. Xenon-fluorine bond lengths of 1.971(7), 1.946(5), 1.958(7), 2.052(5), and 2.099(5) angstroms were found.


Activation of protein kinase C inhibits human keratinocyte migration.
The involvement of protein kinase C (PKC) in epidermal growth factor (EGF)-induced human keratinocyte migration was studied with the phagokinetic assay. It was concluded that PKC activation does not mediate, but rather inhibits, EGF-induced keratinocyte migration. The following experimental observations support these conclusions: 1) The PKC inhibitor H-7 did not inhibit EGF-induced migration but instead led to a modest enhancement. 2) PKC activators such as phorbol-12-myristate-13-acetate (PMA), phorbol-12,13-dibutyrate (PDBu), and 1,2-dioctanoly-sn-glycerol inhibited migration, but biologically inactive 4 alpha-PMA had no effect. 3) PMA did not inhibit keratinocyte attachment and spreading but blocked migration almost immediately after addition. 4) Migration of PKC-depleted cells, which were produced by prolonged treatment with PDBu, was enhanced similarly to normal cells by EGF. 5) PKC-depleted cells were not susceptible to the inhibitory effects of phorbol esters on migration. Additional experiments, in which cells were preactivated with EGF, suggested that PKC inhibits the EGF effect at a post-receptor level. The inhibitory effect of PKC on keratinocyte migration was not restricted to EGF-induced migration; PKC activation also inhibited keratinocyte migration induced by bovine pituitary extract, insulin, insulin-like growth factor-1, and keratinocyte growth factor.


Diet-Related Risk Factors for Incident Hypertension During an 11-Year Follow-Up: The Korean Genome Epidemiology Study.
Using long-term follow-up cohort data from the Korean Genome Epidemiology Study, we assessed the dietary risk factors for incident hypertension (HTN). In total, 6792 subjects (3300 males and 3492 females) aged 40⁻69 years were included in the study. Physician-diagnosed HTN self-reported by the participants was used as the outcome. Daily intake of 20 food groups was assessed while using a dish-based semi-quantitative food-frequency questionnaire. After controlling for known risk factors, the food groups that were most closely associated with HTN were identified by forward stepwise selection while using the Cox proportional hazards model. The median follow-up period was 11.5 years (interquartile range, 6.0⁻11.7 years) and the incidence of HTN was 20 per 1000 person-years. Older age, obesity, lower education level, high alcohol intake, and having at least one parent with HTN were associated with the risk for HTN. In addition, a high intake of salted seafood and a low intake of eggs and meat were independently associated with the incidence of HTN after controlling for the known risk factors. Those in the top quartile of salted seafood intake had a 28% greater risk for incident HTN than those in the bottom quartile. The population-attributable fraction of three dietary factors accounted for 29.0% of the incidence of HTN. A high intake of salted seafood and a low intake of eggs and meat were associated with a greater risk for HTN.


Characterization of newly synthesized proteoglycans from rabbit menisci in organ culture.
Rabbit menisci were incubated with Na2 35SO4 in short-term organ culture to label newly synthesized proteoglycans. The radioactive products present in both tissue and culture medium were characterized separately with respect to distribution after ultracentrifugation in CsCl isopycnic density gradients, hydrodynamic size, interaction with hyaluronic acid, and glycosaminoglycan composition (types, size and content). Analysis of proteoglycan size by gel-filtration chromatography of the most-dense CsCl fractions (A1) on Sephacryl S-500 (associative conditions) resolved three species. A peak with Kav. approx. 0.7 was present in each chromatogram, and constituted the principal component in tissue extracts. Two other peaks with Kav. values of approx. 0.2 and 0.45 were also found. When the A1 fraction from tissue was subjected to CsCl-density-gradient ultracentrifugation under dissociative conditions, 71% of the recovered radioactivity was present in the most dense (A1D1) fraction. Incubation with hyaluronic acid of either A1 or A1D1 fraction from associative extract did not alter the apparent size of the labelled product, indicating a lack of aggregate formation. Meniscal proteoglycans showed an unusual and marked tendency to adsorb irreversibly to agarose and agarose-containing gel-filtration-chromatography media. High-pressure liquid-chromatographic analyses indicated that the sulphated glycosaminoglycans consisted of chondroitin 6-sulphate (72%), chondroitin 4-sulphate (19%) and dermatan sulphate (5%). Endo-beta-galactosidase (keratanase) digestion of the material failed to detect the presence of keratan sulphate. Of the labelled glycosaminoglycans, 95% was eluted from Sephacryl S-400 as a single symmetrical peak with a Kav. of 0.5. The results of studies with tissue extracts and culture medium were similar.


The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.
Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.


Radiation-induced DNA repair foci: spatio-temporal aspects of formation, application for assessment of radiosensitivity and biological dosimetry.
Several proteins involved in DNA repair and DNA damage signaling have been shown to produce discrete foci in response to ionizing radiation. These foci are believed to co-localize to DSB and referred to as ionizing radiation-induced foci (IRIF) or DNA repair foci. Recent studies have revealed that some residual IRIF remain in cells for a relatively long time after irradiation, and have indicated a possible correlation between radiosensitivity of cells and residual IRIF. Remarkably, residual foci are significantly larger in size than the initial foci. Increase in the size of IRIF with time upon irradiation has been found in various cell types and has partially been correlated with dynamics and fusion of initial foci. Although it is admitted that the number of IRIF reflect that of DSB, several studies report a lack of correlation between kinetics for IRIF and DSB and a lack of co-localization between DSB repair proteins. These studies suggest that some proportion of residual IRIF that depend on cell type, dose, and post-irradiation time may represent alternations in chromatin structure after DSB have been repaired or misrepaired. While precise functions of residual foci are presently unknown, their possible link to remaining chromatin alternations, nuclear matrix, apoptosis, delayed repair and misrejoining of DSB, activity of several kinases, phosphatases, and checkpoint signaling has been suggested. Another intriguing possibility is that some of DNA repair foci may mark break-points at chromosomal aberrations (CA). While this possibility has not been confirmed substantially, the residual foci seem to be useful for biological dosimetry and estimation of individual radiosensitivity in radiotherapy of cancer.


Disability and Self-care Living Strategies Among Adults Living With HIV During the COVID-19 Pandemic.
BackgroundEvents associated with the COVID-19 pandemic, such as physical distancing, closure of community services, postponement of health appointments, and loss of employment can lead to social isolation, financial uncertainty, and interruption of antiretroviral adherence, resulting in additional health-related challenges (disability) experienced among adults living with chronic illness such as HIV. 'Living strategies' is a concept derived from the perspective of people living with HIV, defined as behaviors, attitudes and beliefs adopted by people living with HIV to help deal with disability associated with HIV and multi-morbidity. Our aim was to describe disability among adults living with HIV and self-care living strategies used during the COVID-19 pandemic. MethodsAdults living with HIV in Toronto, Ontario, Canada, including some with pre-pandemic HIV Disability Questionnaire (HDQ) data, completed a cross-sectional web-based survey between June-August 2020. The survey included the HDQ and questions about self-care living strategy use during the pandemic. We compared disability (HDQ) scores prior to versus during the pandemic using paired t-tests. We reported the proportion of participants who engaged in various living strategies at least 'a few times a week' or 'everyday' during the pandemic. ResultsOf the 63 respondents, 84% were men, median age 57 years, and 62% lived alone. During the pandemic the greatest disability severity was in the uncertainty (median 30; Interquartile range (IQR): 16, 43) and mental-emotional (25; IQR: 14, 41) domains. Among the 51 participants with pre-pandemic data, HDQ severity scores were significantly greater (worse) during the pandemic (vs prior) in all domains. Greatest change from prior to during the pandemic was in the mental-emotional domain for presence (17.7; p<0.001), severity (11.4; p<0.001), and episodic nature (9.3; p<0.05) of disability. Most participants (>60%) reported engaging a 'few times a week' or 'everyday' in self-care strategies associated with maintaining sense of control and adopting positive attitudes and beliefs. ConclusionsPeople living with HIV reported high levels of uncertainty and mental-emotional health challenges during the pandemic. Disability increased across all HDQ dimensions, with the greatest worsening in the mental-emotional health domain. Results provide an understanding of disability and self-care strategy use during the COVID-19 pandemic.


Human immunodeficiency virus type 1 NL4-3 replication in four T-cell lines: rate and efficiency of entry, a major determinant of permissiveness.
Single-cycle infections have been used to study the human immunodeficiency virus type 1 (HIV-1) life cycle in CD4+ T-cell lines that differ in their permissiveness for infection. In single-cycle infections of highly permissive C8166 cells, 50% of the infectious units escaped being blocked by a monoclonal antibody against the virus binding site on CD4 (leu3a) within 30 min. In contrast, 50% of the infectious units for three less permissive cell lines (H9, A3.01, and Jurkat) required 4 h to escape the leu3a block. Entry was also more efficient in the highly permissive cells, with NL4-3 stocks having three times more infectious units for C8166 cells than for H9, A3.01, or Jurkat cells. Postentry steps up through reverse transcription required approximately 3.5 h in each of the cell lines. The times lapsing between reverse transcription and the expression of reverse transcripts ranged from 17 to 25 h in the different cell lines. Virus production per cell was also similar in the different cell lines (within 1.5-fold of each other). These results indicate that a major determinant of the permissiveness of growing T cells for HIV-1 is the rate and efficiency of virus entry.


Hemodynamic benefit of rest and exercise optimization of cardiac resynchronization therapy.
The optimal method of cardiac resynchronization therapy (CRT) optimization is as yet unknown. We sought to investigate the responses of optimization at rest and on exercise. This 2 stage study involved 59 patients (age 65 ± 10, 75% male), who had all recently undergone successful CRT implantation. In the first stage, the 6-month response was compared between 30 individuals who underwent resting echocardiographic optimization of CRT [atrioventricular (AV delay) plus ventriculo-ventricular delays (VV delay)], compared with the 29 who did not. In the second stage, a subset of 37 patients from the original cohort were randomized (double-blind) to either resting echocardiographic optimization (n = 20) or exercise echocardiographic optimization (n = 17) and followed for a further 6 months. Clinical and echocardiographic data were collected at each stage. Patients undergoing rest optimization demonstrated improvement in almost all variables and significantly in B-type natriuretic peptide (BNP) in contrast to those without optimization. In a linear regression model, the only significant predictor of BNP change was whether an individual underwent resting optimization or not (β = 0.38, P = 0.04). In those undergoing resting optimization, the degree of change in AV delay was correlated with improvement in left ventricle (LV) end-diastolic volume (r(2) = 0.33, P < 0.01). Optimization on exercise was associated with a significant decrease in 6-minute walk test compared to those randomized to rest optimization possibly due to inducing nonoptimization at rest. In conclusion, echocardiographic optimization of CRT at rest is superior to no optimization or optimization on exercise. Patients with the greatest change in AV delay to reach optimal may undergo greater LV remodeling.


Pools versus Queues: The Variable Dynamics of Stochastic "Steady States".
Mathematical models in ecology and epidemiology often consider populations "at equilibrium", where in-flows, such as births, equal out-flows, such as death. For stochastic models, what is meant by equilibrium is less clear--should the population size be fixed or growing and shrinking with equal probability? Two different mechanisms to implement a stochastic steady state are considered. Under these mechanisms, both a predator-prey model and an epidemic model have vastly different outcomes, including the median population values for both predators and prey and the median levels of infection within a hospital (P < 0.001 for all comparisons). These results suggest that the question of how a stochastic steady state is modeled, and what it implies for the dynamics of the system, should be carefully considered.


Familial breast cancer: Genetic counseling over time, including patients´ expectations and initiators considering the Angelina Jolie effect.
The German Consortium for hereditary breast/ovarian cancer (GC-HBOC) aims for nationwide access to professional, individualized yet structured care for families at high risk. The identification of such families remains key for optimal care. Our study evaluates counselees' characteristics, referral practices, expectations and motivations in respect to their first genetic consultation. The impact of the Angelina Jolie Effect (AJE) was prospectively assessed. All counselees could participate through a questionnaire. Groups were built in respect to neoadjuvant chemotherapy (FT) and before/after AJE. The 917 (88.5%) counselees (FT: 8.2%) were on average female (97.3%), with a mean age of 44.6, had children (71.9%), higher education (88%), personal (46.4%) or at least one first-degree relative (74.6%) with BC/OC or known BRCA1/2 mutation (11.8%), were in a relationship (76.1%), and living in a village (40.7%). The AJE is associated with significantly fewer cancelations (p = 0.005), more attendance among men (4.2% vs. 0.8%, p = 0.002), and people with familial BRCA1/2 (14.8% vs. 7.5%, p = 0.003). The majority seek information regarding their cancer risk (83%) or relatives' risk (74.8%), HBOC (69.1%), and surveillance programs for themselves (66.6%) or relatives (60.6%). Enhanced media awareness of genetic cancer motivates patients, including other patient groups. A higher number of participants, including more men, are attending GC due to the AJE. In terms of the rising complexity of genetic testing, the analysis of patients' expectations and initiators for GC suggests that there is an urgent need to develop to participate motivation analysis. The factors revealed as impediments to accessing GC-HBOC guide recommendations to optimize access to genetic counseling. Medical educational programs for primary gynecologists and families at risk might be options to reach more participants.


Classification of coronary artery bifurcation lesions and treatments: time for a consensus!
Percutaneous coronary intervention (PCI) of coronary bifurcation lesions remains a subject of debate. Many studies have been published in this setting. They are often small scale and display methodological flaws and other shortcomings such as inaccurate designation of lesions, heterogeneity, and inadequate description of techniques implemented. The aim is to propose a consensus established by the European Bifurcation Club (EBC), on the definition and classification of bifurcation lesions and treatments implemented with the purpose of allowing comparisons between techniques in various anatomical and clinical settings. A bifurcation lesion is a coronary artery narrowing occurring adjacent to, and/or involving, the origin of a significant side branch. The simple lesion classification proposed by Medina has been adopted. To analyze the outcomes of different techniques by intention to treat, it is necessary to clearly define which vessel is the distal main branch and which is (are) the side branche(s) and give each branch a distinct name. Each segment of the bifurcation has been named following the same pattern as the Medina classification. The classification of the techniques (MADS: Main, Across, Distal, Side) is based on the manner in which the first stent has been implanted. A visual presentation of PCI techniques and devices used should allow the development of a software describing quickly and accurately the procedure performed. The EBC proposes a new classification of bifurcation lesions and their treatments to permit accurate comparisons of well described techniques in homogeneous lesion groups.


CT angiography of the celiac trunk: anatomy, variants and pathologic findings.
Celiac trunk variants and pathologies are relatively common occurrences. With the advent of computed tomography (CT) technology, these conditions are being diagnosed with an increased frequency even among asymptomatic patients. CT angiography is used noninvasively for preoperative staging and vascular mapping in patients with pancreatic and hepatobiliary neoplasm. Multidetector-row CT (MDCT) also allows the accurate depiction of the abdominal splanchnic vessels for stenosis, collateral vessels and atherosclerotic plaques. In this study, we describe the normal anatomy and variants of the celiac trunk as well as associated pathologic conditions, such as stenosis, occlusion, aneurysm and median arcuate ligament compression syndrome. The overall aim of this study was to emphasize the clinical importance of these abnormalities.


A single point mutation in a TssB/VipA homolog disrupts sheath formation in the type VI secretion system of Proteus mirabilis.
The type VI secretion (T6S) system is a molecular device for the delivery of proteins from one cell into another. T6S function depends on the contractile sheath comprised of TssB/VipA and TssC/VipB proteins. We previously reported on a mutant variant of TssB that disrupts T6S-dependent export of the self-identity protein, IdsD, in the bacterium Proteus mirabilis. Here we determined the mechanism underlying that initial observation. We show that T6S-dependent export of multiple self-recognition proteins is abrogated in this mutant strain. We have mapped the mutation, which is a single amino acid change, to a region predicted to be involved in the formation of the TssB-TssC sheath. We have demonstrated that this mutation does indeed inhibit sheath formation, thereby explaining the global disruption of T6S activity. We propose that this mutation could be utilized as an important tool for studying functions and behaviors associated with T6S systems.


Autotaxin inhibitors: a patent review (2012-2016).
Autotaxin (ATX) is a secreted enzyme that hydrolyzes lysophosphatidylcholine to lysophosphatidic acid (LPA) and choline. The ATX/LPA axis has received increasing interest in recent years because both the enzyme ATX and the bioactive lipid LPA are involved in various pathological conditions such as tumor progression and metastasis, fibrotic diseases, autoimmune diseases, arthritis, chronic hepatitis, obesity and impaired glucose homeostasis. Thus, a great effort has been devotd in developing synthetic ATX inhibitors as new agents to treat various diseases including cancer and fibrotic diseases. Areas covered: This review article summarizes the autotaxin inhibitors presented in patent literature from October 2012 to August 2016 and their biological evaluation, discussing their activities in vitro and in vivo. Expert opinion: During the recent years, there has been an intensive effort on the discovery of potent and selective ATX inhibitors. Although various synthetic inhibitors have been developed, only limited studies for their in vivo activity have been reported so far. A decade after the first claim of synthetic ATX inhibitors in 2006, one inhibitor has been in clinical trials for idiopapthic pulmonary fibrosis. The use of ATX inhibitors seems an attractive strategy to produce novel medicinal agents, for example anticancer agents.


Australia's deep-water octocoral fauna: historical account and checklist, distributions and regional affinities of recent collections.
The number of deep-water (>80 m) octocoral species recorded from Australian waters has more than tripled from 135 to 457 following six surveys undertaken between 1997 and 2008 on the deep continental margin of south-eastern, western and north-western Australia and the Tasman Sea. This rapid increase in knowledge follows a slow accumulation of records since the earliest collections were made by vessels such as the Géographe and the Naturaliste in the early years of the 19 century. Consistent identification and alpha-labelling of the octocoral fauna between surveys has permitted a multi-region description and comparison. We detail the identities, distributions and regional affinities of 457 octocoral species in 131 genera and 28 families from the orders Alcyonacea and Pennatulacea, including 69 new species, 17 new genera and 43 first records for Australia. Five of the more common genera were widely distributed (present at 35 and 66 sampling stations spanning all of the 4 survey regions), but two were restricted to south-eastern Australia-Pleurogorgia Versluys, 1902 and Tokoprymno Bayer, 1996-and were only sampled from depths below 700 m. The great majority of species (81%) and nearly half of all genera (47%) were only sampled once or twice. The highest average number of species per sampling station (3.2) was reported from the outer shelf. The proportion of new species was highest (22%) on the upper and lower slope bathomes, intermediate (13-15%) on the mid-slope bathome and lowest (8%) on the outer shelf bathome. Species overlap between bathomes was low, but all families were shared across bathomes. Most described species (55 of 69) have an Indo-West Pacific affinity, 20 have an Indian Ocean affinity, while three were previously recorded from the Atlantic Ocean only; 20 appear to be Australian endemics. Octocorals can now be added to an emerging set of taxon-specific data sets-including fishes, ophiuroids and galatheids-that permit regional-scale analysis of biodiversity distributions to support Australia's efforts in marine conservation management. However, because so much of the world octocoral literature is inadequate for accurate identifications to species level, there is a pressing need for taxonomic revisions using modern morphological and molecular techniques to fine-tune the current use of octocorals as indicators of vulnerable marine ecosystems in many national and high seas conservation initiatives.


Infections and treatment of patients with rheumatic diseases.
Glucocorticoids (GCs) have many complex quantitative and qualitative immunosuppressive effects which induce cellular immunodeficiency and increase host susceptibility to various viral, bacterial, fungal and parasitic infections. As cortisol secretion is inadequate in chronic immune/inflammatory conditions, and current therapies have the aim of providing adequate (low) compensatory doses, the timing of GC administration, such as during the nocturnal turning-on phase of tumour necrosis factor (TNF) secretion, can be extremely important. The use of the lowest possible GC dose, at night, and for the shortest possible time should therefore greatly reduce the risk of infections. Infection is a major co-morbidity in rheumatoid arthritis (RA), and conventional disease-modifying anti-rheumatic drugs (DMARDs) can increase the risk of their occurrence, including tuberculosis. TNF-alpha plays a key role in the pathogenesis of RA, and the data concerning infections in RA patients treated with anti-TNF agents are controversial. Patients and physicians should vigilantly monitor for signs of infection when using anti-TNF agents. Recombinant gene technologies now make it possible to produce protein drugs that are almost identical to naturally occurring human polypeptides, including antibody (Ab) constructs; unfortunately, all human biological agents are potentially immunogenic. An increasing number of recent studies have demonstrated the safety of influenza and pneumococcal vaccines administered to patients with systemic lupus erythematosus (SLE) or RA. These vaccinations are generally immunogenic (i.e., capable of inducing a protective level of specific antibodies) but may not induce an adequate response in a substantial proportion of patients.


Fine-structural studies of the gametes and embryo of Fucus vesiculosus L. (Phaeophyta). I. Fertilization and pronuclear fusion.
In the marine brown alga, Fucus vesiculosus L., the sperm pronucleus is delimited by an envelope following penetration of the eff by the sperm. This envelope disintegrates as the pronucleus begins its migration through the cytoplasm of the egg. The highly condensed chromatin of the sperm pronucleus disperses slightly following disintegration of the envelope. Microtubules of unknown origin are associated with the sperm pronucleus during its migration. The flagellar microtubules remain in the peripheral cytoplasm but lose their tight 9 + 2 configuration. The sperm eyespot and mitochondria follow the pronucleus through the cytoplasm toward the egg pronucleus. The mitochondria of the sperm are distinguished from those of the egg by their longitudinally oriented cristae and by electron-opaque material in the intracristal space. The pronucleus of the egg becomes convoluted along the surface nearest to the advancing sperm pronucleus. Immediately prior to pronuclear fusion, many egg mitochondria aggregate in the vicinity of the sperm pronucleus. At this time, only the portion of the sperm pronucleus facing the egg pronucleus is surrounded by an envelope. The egg mitochondria disperse rapidly after pronuclear fusion. The sperm mitochondria and eyespot are still in the perinuclear region in 16-h-old embryos. At this time, the osmiophilia of the sperm eyespot has increased, and the sperm mitochondrial membranes are less distinct than in earlier stages. The fine-structural features of fertilization in Fucus are discussed in relation to the fertilization patterns in other cryptogams and marine invertebrates and to polar axis determination in the Fucaceae.


Does patient history and physical examination predict MRI proven cauda equina syndrome?
Systematic review. While magnetic resonance imaging (MRI) is used as the diagnostic gold standard for cauda equina syndrome (CES), many MRI scans obtained from patients presenting with signs and/or symptoms of CES do not reveal concordant pathology. As a result, the role of the history and physical examination remains unclear when determining which patients require emergent MRI.Objective or clinical question: Are there elements from the history or physical examination that are associated with CES as established by MRI? A systematic review of the literature was undertaken for articles published through April 13, 2011. PubMed, Cochrane, National Guideline Clearinghouse Databases, and bibliographies of key articles were searched. Two independent reviewers reviewed articles. Inclusion and exclusion criteria were set and each article was subject to a predefined quality-rating scheme. We identified four articles meeting our inclusion criteria. All studies evaluated patients with symptoms suggestive of CES and compared symptoms and/or signs with findings at MRI. The mean prevalence of CES as diagnosed by MRI ranged from 14%-48% of patients. No symptoms or signs reported by more than one study showed high sensitivity and specificity, and all likelihood ratios were low. Symptoms included back/low back pain, bilateral sciatica, bladder retention, bladder incontinence, frequent urination, decreased urinary sensation, and bowel incontinence; signs included saddle numbness and reduced anal tone. There is low evidence that individual symptoms or signs from the patient history or clinical examination, respectively, can be used to diagnose CES. Additional prospective studies are needed to evaluate whether any single and/or combination of symptoms are associated with a positive diagnosis of CES.


Pancreatic carcinosarcoma: case report of a rare type of pancreatic neoplasia.
Carcinosarcoma of the pancreas is a rare entity comprising a small subset of all pancreatic neoplasms. Diagnosis is usually established by immunohistochemical examination of the resected specimen. Prognosis is limited to several months after resection. We review the current literature on this rare type of neoplasia, considering histopathological and clinical features. The pathologic findings revealed areas of both adenocarcinoma and sarcoma of the pancreas. The adenocarcinomatous areas localized to the tumor within the head of the pancreas whereas the sarcomatous areas localized to regions of the intraductal component. Carcinosarcoma of the pancreas is a rare disease having a dismal prognosis. To our knowledge, this carcinosarcoma is the very rare reported case of a primary pancreatic neoplasm with mixed carcinomatous and sarcomatous components.


The evaluation of the effects of renal failure on erectile dysfunction in a rabbit model of chronic renal failure.
To determine whether chronic renal failure (CRF) reduces nitrergic relaxant responses in a rabbit model. Ten rabbits underwent surgery to induce uraemia (CRF rabbits) and a further 10 a sham operation (controls). Corpus cavernosal tissue was prepared and used in organ-chamber experiments, with relaxation assessed against a background of pre-contraction with phenylephrine. At the plateau of contraction, relaxation responses to cumulative concentrations of carbachol or sodium nitroprusside (SNP), to test endothelium-dependent and -independent relaxations, respectively, were assessed. Before electrical-field stimulation (EFS), the tissue was treated with an adrenergic nerve blocker and a muscarinic receptor blocker to eliminate the adrenergic and cholinergic components, and to determine the relaxation responses to the stimulation of nonadrenergic, noncholinergic (NANC) nerves. The relaxation responses in corporal strips obtained from CRF rabbits were compared with those from controls. When tissues were contracted with KCl, tensions were similar in all groups. The impairment in concentration-dependent relaxation with carbachol was significant in CRF rabbits, but SNP- and papaverine-induced concentration-dependent relaxation responses were no different among the groups. EFS-induced frequency-dependent relaxations were significantly lower in CRF rabbits than in controls. CRF inhibits the NANC-mediated relaxation of rabbit corpus cavernosum smooth muscle. Changes in NANC-mediated and carbachol-induced (endothelium-dependent) relaxation of corporal smooth muscle in the rabbit are probably caused by uraemia and subsequently, hyperthyroidism, hyperparathyroidism or low testosterone levels in CRF. These results also suggest that if vasoactive agents are to be used for treating erectile dysfunction in uraemic patients, direct-acting vasodilators and phosphodiesterase inhibitors will be useful.


Characterization of complexes containing protein A and rabbit immunoglobulin G or Fc gamma fragments.
Soluble complexes prepared over a range of molar ratios of [125I] protein A (SpA) and rabbit [131I]immunoglobulin G (IgG) or [131I]Fc gamma fragments were separated by ultracentrifugation in a sucrose gradient and selectively radioimmunoprecipitated with chicken antibodies that bind free or complexed SpA. With excess [125I]SpA the only complexes formed were composed of one molecule of labeled ligand and one molecule of [125I]SpA (1:1 complexes). With excess ligand the only complexes formed corresponded to [(IgG)2SpA]2 or [(Fc gamma)2SpA]2 (4:2 complexes). The 4:2 complex likely is responsible for several of the biological activities associated with SpA, including activation of humoral and cellular immune mechanisms, which are optimal under conditions of excess IgG.