The representation of periodic sounds in simulated sustained chopper units of the ventral cochlear nucleus.
The nature of the neural processing underlying the extraction of pitch information from harmonic complex sounds is still unclear. Electrophysiological studies in the auditory nerve and many psychophysical and modeling studies suggest that pitch might be extracted successfully by applying a mechanism like autocorrelation to the temporal discharge patterns of auditory-nerve fibers. The current modeling study investigates the possible role of populations of sustained chopper (Chop-S) units located in the mammalian ventral cochlear nucleus (VCN) in this process. First, it is shown that computer simulations can predict responses to periodic and quasiperiodic sounds of individual Chop-S units recorded in the guinea-pig VCN. Second, it is shown that the fundamental period of a periodic or quasiperiodic sound is represented in the first-order, interspike interval statistics of a population of simulated Chop-S units. This is true across a wide range of characteristic frequencies when the chopping rate is equal to the f0 of the sound. The model was able to simulate the results of psychophysical studies involving the pitch height and pitch strength of iterated ripple noise, the dominance region of pitch, the effect of phase on pitch height and pitch strength, pitch of inharmonic stimuli, and of sinusoidally amplitude modulated noise. Simulation results indicate that changes in the interspike interval statistics of populations of Chop-S units compare well with changes in the pitch perceived by humans. It is proposed that Chop-S units in the ventral cochlear nucleus may play an important role in pitch extraction: They can convert a purely temporal pitch code as observed in the auditory nerve into a temporal place code of pitch in populations of cochlear-nucleus, Chop-S with different characteristic frequencies, and chopping rates. Thus, populations of cochlear-nucleus Chop-S units, together with their target units presumably located in the inferior colliculus, may serve to establish a stable rate-place code of pitch at the level of the auditory cortex.


Differential targeting of beta -adrenergic receptor subtypes and adenylyl cyclase to cardiomyocyte caveolae. A mechanism to functionally regulate the cAMP signaling pathway.
Differential modes for beta(1)- and beta(2)-adrenergic receptor (AR) regulation of adenylyl cyclase in cardiomyocytes is most consistent with spatial regulation in microdomains of the plasma membrane. This study examines whether caveolae represent specialized subdomains that concentrate and organize these moieties in cardiomyocytes. Caveolae from quiescent rat ventricular cardiomyocytes are highly enriched in beta(2)-ARs, Galpha(i), protein kinase A RIIalpha subunits, caveolin-3, and flotillins (caveolin functional homologues); beta(1)-ARs, m(2)-muscarinic cholinergic receptors, Galpha(s), and cardiac types V/VI adenylyl cyclase distribute between caveolae and other cell fractions, whereas protein kinase A RIalpha subunits, G protein-coupled receptor kinase-2, and clathrin are largely excluded from caveolae. Cell surface beta(2)-ARs localize to caveolae in cardiomyocytes and cardiac fibroblasts (with markedly different beta(2)-AR expression levels), indicating that the fidelity of beta(2)-AR targeting to caveolae is maintained over a physiologic range of beta(2)-AR expression. In cardiomyocytes, agonist stimulation leads to a marked decline in the abundance of beta(2)-ARs (but not beta(1)-ARs) in caveolae. Other studies show co-immunoprecipitation of cardiomyocytes adenylyl cyclase V/VI and caveolin-3, suggesting their in vivo association. However, caveolin is not required for adenylyl cyclase targeting to low density membranes, since adenylyl cyclase targets to low buoyant density membrane fractions of HEK cells that lack prototypical caveolins. Nevertheless, cholesterol depletion with cyclodextrin augments agonist-stimulated cAMP accumulation, indicating that caveolae function as negative regulators of cAMP accumulation. The inhibitory interaction between caveolae and the cAMP signaling pathway as well as domain-specific differences in the stoichiometry of individual elements in the beta-AR signaling cascade represent important modifiers of cAMP-dependent signaling in the heart.


Solid-phase extractors based on 8-aminoquinoline and 2-aminopyridine covalently bonded to silica gel for the selective separation and determination of calcium in natural water and pharmaceutical samples.
Two new silica-gel phases were produced directly via the chemical interaction of 3-chloropropyltrimethoxysilane modified silica gel with 8-aminoquioline, phase I and 2-aminopyridine, phase II under reflux conditions. The selectivity properties exhibited by the phases under investigation for the uptake of Ca(II), Mg(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Pb(II) were determined at different pH values and shaking times under static conditions. The immobilization process and binding of metal ions to the phases were proved via infrared spectra. The phases showed high performance towards Ca(II) extraction at pH 10.00. The equilibrium data were better fitted with a Langmuir model (r(2) = 0.985). The adsorption kinetics data were best fitted with the pseudo-second-order type. Good validation was obtained on applications of the two phases for the separation and determination of Ca(II) in natural water and pharmaceutical samples with no matrix interferences at pH 10.00 under dynamic conditions prior to determination by AAS.


Nongastrointestinal symptoms of irritable bowel syndrome: an office-based clinical survey.
Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal problem faced by practicing gastroenterologists. For many years, nongastrointestinal symptoms have been documented in IBS patients, but the medical literature does not emphasize them. The present study explored how IBS and inflammatory bowel disease patients differ in their reporting of nongastrointestinal symptoms. Information from 200 consecutive patients with IBS and a similar number of patients with Crohn's disease (in a single gastroenterology practice) was obtained at the initial visit using a simple questionnaire. Comparison of the data revealed that IBS patients describe certain nongastrointestinal symptoms far more frequently than do those with inflammatory bowel disease. It is recommended that these symptoms be considered along with the generally accepted criteria for making a positive diagnosis of IBS.


Agrobacterium-mediated transient transformation of sorghum leaves for accelerating functional genomics and genome editing studies.
Sorghum is one of the most recalcitrant species for transformation. Considering the time and effort required for stable transformation in sorghum, establishing a transient system to screen the efficiency and full functionality of vector constructs is highly desirable. Here, we report an Agrobacterium-mediated transient transformation assay with intact sorghum leaves using green fluorescent protein as marker. It also provides a good monocot alternative to tobacco and protoplast assays with a direct, native and more reliable system for testing single guide RNA (sgRNA) expression construct efficiency. Given the simplicity and ease of transformation, high reproducibility, and ability to test large constructs, this method can be widely adopted to speed up functional genomic and genome editing studies.


Aggregate formation of hepatitis B virus X protein affects cell cycle and apoptosis.
To investigate whether the formation of aggregated HBx has a potential linking with its cellular responses. Recombinant HBx was expressed in Escherichia coli and purified by Ni-NTA metal-affinity chromatography. Anti-HBx monoclonal antibody was developed for immunocytochemical detection. Bicistronic expression vector harboring full-length DNA of HBx was employed for transfection of human HepG2 cells. Immunocytochemical staining was used to examine the intracellular HBx aggregates in cells. The effects of HBx aggregation on cell cycle and apoptosis were assessed by flow cytometry. Immunocytochemical staining revealed most of the HBx was formed intracellular aggregate in cytoplasm and frequently accumulated in large granules. Flow cytometry analysis showed that HepG2 cells transfected with vector harboring HBx significantly increased apoptosis and largely accumulated in the G0-G1 phase by maintenance in serum medium for 36 hours. Control cells without HBx aggregates in the presence of serum entered S phase and proliferated more rapidly at the same time. EGFP fluorescence in HBx expression cells was significantly decreased. Our observations show that cells with HBx aggregate undergo growth arrest and apoptosis, whereas control cells without HBx remain in growth and progression into S phase. Our data may provide helpful information to understand the biological effects of HBx aggregates on cells.


Depressive Symptoms and Their Relation to Age and Chronic Diseases Among Middle-Aged and Older Adults in Rural South Africa.
Understanding how depression is associated with chronic conditions and sociodemographic characteristics can inform the design and effective targeting of depression screening and care interventions. In this study, we present some of the first evidence from sub-Saharan Africa on the association between depressive symptoms and a range of chronic conditions (diabetes, HIV, hypertension, and obesity) as well as sociodemographic characteristics. A questionnaire was administered to a population-based simple random sample of 5,059 adults aged 40 years and older in Agincourt, South Africa. Depressive symptoms were measured using a modified version of the eight-item Center for Epidemiological Studies-Depression screening tool. Diabetes was assessed using a capillary blood glucose measurement and HIV using a dried blood spot. 17.0% (95% confidence interval: 15.9%-18.1%) of participants had at least three depressive symptoms. None of the chronic conditions were significantly associated with depressive symptoms in multivariable regressions. Older age was the strongest correlate of depressive symptoms with those aged 80 years and older having on average 0.63 (95% confidence interval: 0.40-0.86; p < .001) more depressive symptoms than those aged 40-49 years. Household wealth quintile and education were not significant correlates. This study provides some evidence that the positive associations of depression with diabetes, HIV, hypertension, and obesity that are commonly reported in high-income settings might not exist in rural South Africa. Our finding that increasing age is strongly associated with depressive symptoms suggests that there is a particularly high need for depression screening and treatment among the elderly adults in rural South Africa.


Polyploid amphibians: three more diploid-tetraploid cryptic species of frogs.
The nominal African species Pyxicephalus delalandii and Dicroglossus occipitalis have diploid and tetraploid populations. There are also cryptic tetraploid and diploid species similar to Bufo kerinyagae. These represent the first bisexual polyploid "species" so far encountered in the major frog families Ranidae and Bufonidae. The contention that polyploidy is a widespread and important evolutionary phenomenon in anuran amphibians is supported.


Dynamic right ventricular dimension. Relation to chamber volume during the cardiac cycle.
Whereas the left ventricle has been analyzed extensively, the apparent complexity of right ventricular geometry and contraction has hindered analysis of right ventricular performance by an assessment of instantaneous ventricular dimensions and volume during the cardiac cycle. To address this issue, we examined the temporal and quantitative relation between dynamic right ventricular free wall dimension, rate of pressure development (dP/dt), and pulmonary artery flow in the open-chest dog. Right ventricular free wall chord dimension was recorded by sonomicrometry, right ventricular pressure by micromanometer-tipped catheter, and pulmonary flow by electromagnetic probe. The point of peak positive right ventricular dP/dt closely correlated with the end of isovolumic contraction and initiation of ejection, occurring within 10 +/- 25 msec of initiation of pulmonary flow. Right ventricular dimension at peak positive dP/dt differed from dimension at initiation of chord shortening by less than 3%. Peak negative dP/dt correlated with end ejection, occurring within 10 +/- 25 msec of cessation of pulmonary flow. Right ventricular dimension at peak negative dP/dt differed from minimal dimension by less than 1%. In all dogs, volume ejected from the right ventricular chamber during each cardiac cycle was directly related to the change in right ventricular dimension during the same period (mean r = 0.969). This relationship between right ventricular stroke volume and dimensional change remained linear and was not changed (p = NS) by increases in right or left ventricular afterload induced by constricting the pulmonary artery or descending aorta. Right ventricular stroke work, calculated as the integral of instantaneous right ventricular pressure and dimension, correlated well (mean r = 0.980) with directly measured global right ventricular stroke work over a wide range; it was also not changed (p = NS) by changes in afterload. Accurate assessments of beat-to-beat right ventricular chamber volume and stroke work can be obtained by analysis of dynamic right ventricular chord dimension.


Quantitative parameters determining whitefly (Bemisia tabaci) transmission of Lettuce infectious yellows virus and an engineered defective RNA.
In this study, quantitative parameters affecting in vitro acquisition and whitefly (Bemisia tabaci) transmission of Lettuce infectious yellows virus (LIYV) were examined and B. tabaci transmission of an engineered defective RNA (D-RNA) was demonstrated. Virions purified from virus- and virion RNA-inoculated Chenopodium murale plants and protoplasts of Nicotiana tabacum, respectively, were consistently transmitted to plants by B. tabaci when virion concentrations were 0.1 ng microl(-1) or greater. Transmission efficiency increased with increasing virion concentration and number of whiteflies used for inoculation. When in vitro-derived transcripts of the M5gfp D-RNA (engineered to express the green fluorescent protein, GFP) were co-inoculated to protoplasts with wild-type LIYV virion RNAs, the resulting virions were transmissible to plants. LIYV and the M5gfp D-RNA systemically invaded inoculated plants; however, GFP expression was not detected in these plants. Unlike LIYV, the M5gfp D-RNA was not subsequently transmitted by B. tabaci from the initially infected plants, but, when high concentrations of virions from plants infected by LIYV and the M5gfp D-RNA were used for in vitro acquisition by whiteflies, both were transmitted to plants. Quantitative and qualitative analyses showed that, although the M5gfp D-RNA replicated within and systemically invaded plants along with LIYV, compared with LIYV RNA 2 it was not as abundant in plants or in the resulting virions, and concentration of encapsidated RNAs is an important factor affecting transmission efficiency.


Inhibitory receptors CD85j, LAIR-1, and CD152 down-regulate immunoglobulin and cytokine production by human B lymphocytes.
Class switching consists in the substitution of the heavy-chain constant region of immunoglobulin M (IgM) with that of IgG, IgA, or IgE. This enables antibodies to acquire new effector functions that are crucial to combat invading pathogens. Class switching usually requires engagement of CD40 on B cells by CD40 ligand (CD40L) on antigen-activated CD4(+) T cells and the production of cytokines. The process must be regulated tightly because abnormal IgG and IgA production favors the onset of autoimmunity, whereas increased switching to IgE leads to atopy. These inflammatory disorders can be triggered or exacerbated by costimulatory signals. Although thoroughly investigated on T cells, the roles of the inhibitory receptors CD85j, LAIR-1, and CD152 on B-cell functions have not been fully elucidated. In this study we show that cross-linking of the B-cell inhibitory receptors by specific monoclonal antibodies inhibits IgG and IgE production, reduces the percentage of IgG- and IgE-expressing B cells, and down-regulates interleukin 8 (IL-8), IL-10, and tumor necrosis factor alpha production. These effects were demonstrated using different B-cell stimulatory pathways (recall antigens, CD40L-transfected cells plus IL-4, and lipopolysaccharide plus IL-4). It thus appears that CD85j, LAIR-1, and CD152 play a central role for the control of IL-4-driven isotype switching.


Examining Predictors of Myocardial Infarction.
Cardiovascular diseases are the leading cause of death in the United States. This study analyzed predictors of myocardial infarction (MI) for those aged 35 and older based on demographic, socioeconomic, geographic, behavioral, and risk factors, as well as access to healthcare variables using the Center for Disease (CDC) Control Behavioral Risk Factor Surveillance System (BRFSS) survey for the year 2019. Multiple quasibinomial models were generated on an 80% training set hierarchically and then used to forecast the 20% test set. The final training model proved somewhat capable of prediction with a weighted F1-Score = 0.898. A complete model based on statistically significant variables using the entirety of the dataset was compared to the same model built on the training set. Models demonstrated coefficient stability. Similar to previous studies, age, gender, marital status, veteran status, income, home ownership, employment status, and education level were important demographic and socioeconomic predictors. The only geographic variable that remained in the model was associated with the West North Central Census Division (in-creased risk). Statistically important behavioral and risk factors as well as comorbidities included health status, smoking, alcohol consumption frequency, cholesterol, blood pressure, diabetes, stroke, chronic obstructive pulmonary disorder (COPD), kidney disease, and arthritis. Three access to healthcare variables proved statistically significant: lack of a primary care provider (Odds Ratio, OR = 0.853, p < 0.001), cost considerations prevented some care (OR = 1.232, p < 0.001), and lack of an annual checkup (OR = 0.807, p < 0.001). The directionality of these odds ratios is congruent with a marginal effects model and implies that those without MI are more likely not to have a primary provider or annual checkup, but those with MI are more likely to have missed care due to the cost of that care. Cost of healthcare for MI patients is associated with not receiving care after accounting for all other variables.


Trichomonas vaginalis in a perinephric abscess. A case report.
A patient with chronic vulvo-vaginitis due to Trichomonas vaginalis, and obstructive uropathy associated with renal calculi, developed a perinephric abscess following trauma incurred in a motorcycle accident. T. vaginalis was seen on smear and cultured from the purulent drainage from the perinephric abscess. Although T. vaginalis is commonly pathogenic only to the lower genito-urinary system, the upper urinary tract may very rarely be involved by ascending infection. If this protozoan spreads to extraluminal sites the inflammatory potential is marked, as has been found in animals with experimental infection. Examination of a fresh smear of pus may be critically important in the diagnosis of closed-space infections of unknown etiology.


A role for spleen monocytes in post-ischemic brain inflammation and injury.
Although infiltration of peripheral monocytes/macrophages is implicated in stroke pathology, in vivo data regarding the deployment of monocytes and their mobilization to the infarct area is scarce. Recent literature showed that mouse monocytes exhibit two distinct populations that represent pro-inflammatory (Ly-6Chi/CCR2+) and anti-inflammatory (Ly-6Clow/CCR2-) subsets and that spleen is a major source for monocyte deployment upon injury. By reducing post-ischemic infection with antibacterial moxifloxacin (MFX) treatment, the present study investigates the effect of the treatment on Ly-6C and CCR2 expression in the spleen following ischemia and the extent to which the effect is associated with attenuation of post-ischemic inflammation and injury. Mice subjected to a middle cerebral artery occlusion (MCAO) showed a significant reduction in their spleen weights compared to sham animals. Compared to vehicle controls, splenocytes obtained from daily MFX-treated mice 7 days after ischemia exhibited significantly reduced mean Ly-6C expression within pro-inflammatory subsets, whereas the distribution of pro- and anti-inflammatory subsets was not different between the treatment groups. Additionally, MFX treatment significantly reduced CCR2 expression in the spleen tissue and in the post-ischemic brain and attenuated infarct size. The study suggests a potential contributing role of spleen monocytes in post-ischemic inflammation and injury. The influence of peripheral inflammatory status on the primary injury in the CNS further implies that the attenuation of post-stroke infection may be beneficial in mitigating stroke-induced brain injury.


Refining Current Scientific Priorities and Identifying New Scientific Gaps in HIV-Related Heart, Lung, Blood, and Sleep Research.
The National Heart, Lung, and Blood Institute (NHLBI) AIDS Program's goal is to provide direction and support for research and training programs in areas of HIV-related heart, lung, blood, and sleep (HLBS) diseases. To better define NHLBI current HIV-related scientific priorities and with the goal of identifying new scientific priorities and gaps in HIV-related HLBS research, a wide group of investigators gathered for a scientific NHLBI HIV Working Group on December 14-15, 2015, in Bethesda, MD. The core objectives of the Working Group included discussions on: (1) HIV-related HLBS comorbidities in the antiretroviral era; (2) HIV cure; (3) HIV prevention; and (4) mechanisms to implement new scientific discoveries in an efficient and timely manner so as to have the most impact on people living with HIV. The 2015 Working Group represented an opportunity for the NHLBI to obtain expert advice on HIV/AIDS scientific priorities and approaches over the next decade.


A new species of Brasilotyphlus (Gymnophiona: Siphonopidae) and a contribution to the knowledge of the relationship between Microcaecilia and Brasilotyphlus.
A third species of Brasilotyphlus, a siphonopid caecilian, is described based on six specimens from two twin mountains in Roraima state, northern Brazil. Brasilotyphlus dubium sp. nov. differs from all other congeners in having a combination of 123-129 primary annuli and 9-16 secondary annular grooves. The first molecular data were generated and analyzed for Brasilotyphlus, and the genus was recovered as monophyletic and nested within a paraphyletic Microcaecilia. The extent of genetic and taxonomic sampling, and moderate phylogenetic support are not considered sufficient enough to place Brasilotyphlus in the synonymy of Microcaecilia.


Donepezil medicated memory improvement in traumatic brain injury during post acute rehabilitation.
Memory dysfunction is a recognized and difficult to treat complication of traumatic brain injury (TBI). Since medial-temporal lobe injury is a frequent contributor to memory dysfunction in TBI, it is likely that an acetylcholine deficit contributes to memory dysfunction in this population. Recently, Donepezil, an acetylcholine-esterase inhibitor which has demonstrated a high selectivity for neural Ach-esterase (with minimal side effects), was approved for use in dementia in Alzheimer's patients. Due to its promising results in Alzheimer's patients, and reports in the literature describing the use of physostigmine (an anti-cholinesterase with significant cardiovascular and autonomic side effects) to treat memory deficits in closed head injury, we decided to begin a trial of Donepezil in two patients with TBI who were experiencing long term static memory dysfunction refractory to conventional treatment. Both patients were admitted to our facility for physical and cognitive rehabilitation, and were started on a trial of Donepezil. Modified memory tests and subjective observations by both family and staff pointed to an improvement in memory within three weeks of starting Donepezil. Should these initial results be supported in larger trials, Donepezil may prove to be a valuable tool for the treatment of memory dysfunction in TBI.


Signal processing system to extract serum bilirubin concentration from diffuse reflectance spectrum of human skin.
Neonatal jaundice is a medical condition which occurs in newborns as a result of an imbalance between the production and elimination of bilirubin. Excess bilirubin in the blood stream diffuses into the surrounding tissue leading to a yellowing of the skin. The extra-vascular bilirubin act as interfering signal that limits the estimation of serum bilirubin from reflectance spectrum of human skin. This is particularly an issue for neonates who are being subjected to phototherapy (a common treatment for neonatal jaundice). Unfortunately, analytical models developed to study the light transport in human skin do not consider the effects of extra-vascular bilirubin (and other absorbing chromophores). A biomedical signal processing method that estimates serum bilirubin in presence of confounding signals such as melanin and extra-vascular bilirubin concentrations is presented. The new system model and nonlinear solver have been successful in estimating the serum bilirubin concentration on simulated spectral databases within an average error of 15%.


Effective adsorption of Pb(II) ion from aqueous solution onto ZSM-5 zeolite synthesized from Vietnamese bentonite clay.
ZSM-5 zeolite was successfully synthesized from bentonite clay sourced from Lam Dong Province, Vietnam, using the hydrothermal method at 170 °C for 18 h. The synthesized ZSM-5 (SiO2/Al2O3 ratio ~ 34) exhibited a single phase with high crystallinity (91.8%), and a clear and uniform shape. In a detailed examination of the synthesized material's Pb(II) adsorptive capacity, various factors were taken into account, including pH, interaction time, ionic strength, and the amount of adsorbent. Isotherms and kinetics were examined to elucidate the uptake behavior. Study results suggested that Pb(II) ion uptake by ZSM-5 was most appropriately described by the Sips isotherm and intraparticle diffusion kinetic models. The calculated maximum monolayer adsorption capacity according to the Langmuir isotherm model was 48.36 mg/g. Furthermore, the adsorption mechanisms of Pb(II) on ZSM-5 involving electrostatic interactions, ion exchange, and diffusion into pores were demonstrated using the analytical techniques before and after Pb(II) adsorption. These findings demonstrate that ZSM-5 synthesized from bentonite clay exhibits an excellent adsorption capacity for Pb(II), resulting in promising applications for treating drinking water or aqueous industrial waste containing Pb(II) ions.


Conditionally expressed missense mutations: the basis for the unusual phenotype of an apparent trpD nonsense mutant of Salmonella typhimurium.
Tryptophan auxotroph trpo-28 is anomalous since preliminary mapping and suppression studies indicate the presence of a single amber nonsense mutation either late in trpE or early in trpD, but enzymological tests indicate the complete inactivation of both genes in this strain. Since the trpE and trpD genes are contiguous and encode the two subunits of a multifunctional enzyme complex, it was of interest to learn the mechanism of action of this apparent pleiotropic nonsense mutation. Our study has revealed that the phenotype of this strain derives not from a single mutation, but from the presenc and interaction of multiple mutations. Besides the recognized amber mutation (designated trpD28), this strain carries two additional, conditionally expressed missense mutations (designated trpE1651 and trpD1652). The trpD28 amber codon maps in the promoter-proximal region 1 of trpD and eliminates the glutamine amidotransferase activity of the bifunctional trpD polypeptide. The trpD1652 mutation maps in the promoter-distal region 2 of trpD and severely reduces (but does not eliminate) the phosphoribosyl transferase activity of the trpD polypeptide. The trpE1651 mutation maps in the anterior part of trpE and causes a rapid loss of activity of the trpE polypeptide, but only when it exists as an umcomplexed subunit. The existence of the two missense mutations escaped prior notice in standard recombinational tests since the nature of ech mutation is such that neither is detectable by the nutritional screens normally used in such tests unless an unsuppressed chain-terminating mutation, such as trpD28, is also present.


Trustworthy and Reliable Deep Learning-based Cyberattack Detection in Industrial IoT.
A fundamental expectation of the stakeholders from the Industrial Internet of Things (IIoT) is its trustworthiness and sustainability to avoid the loss of human lives in performing a critical task. A trustworthy IIoT-enabled network encompasses fundamental security characteristics such as trust, privacy, security, reliability, resilience and safety. The traditional security mechanisms and procedures are insufficient to protect these networks owing to protocol differences, limited update options, and older adaptations of the security mechanisms. As a result, these networks require novel approaches to increase trust-level and enhance security and privacy mechanisms. Therefore, in this paper, we propose a novel approach to improve the trustworthiness of IIoT-enabled networks. We propose an accurate and reliable supervisory control and data acquisition (SCADA) network-based cyberattack detection in these networks. The proposed scheme combines the deep learning-based Pyramidal Recurrent Units (PRU) and Decision Tree (DT) with SCADA-based IIoT networks. We also use an ensemble-learning method to detect cyberattacks in SCADA-based IIoT networks. The non-linear learning ability of PRU and the ensemble DT address the sensitivity of irrelevant features, allowing high detection rates. The proposed scheme is evaluated on fifteen datasets generated from SCADA-based networks. The experimental results show that the proposed scheme outperforms traditional methods and machine learning-based detection approaches. The proposed scheme improves the security and associated measure of trustworthiness in IIoT-enabled networks.


A new P450 involved in the furanocoumarin pathway underlies a recent case of convergent evolution.
Furanocoumarins are phytoalexins often cited as an example to illustrate the arms race between plants and herbivorous insects. They are distributed in a limited number of phylogenetically distant plant lineages, but synthesized through a similar pathway, which raised the question of a unique or multiple emergence in higher plants. The furanocoumarin pathway was investigated in the fig tree (Ficus carica, Moraceae). Transcriptomic and metabolomic approaches led to the identification of CYP76F112, a cytochrome P450 catalyzing an original reaction. CYP76F112 emergence was inquired using phylogenetics combined with in silico modeling and site-directed mutagenesis. CYP76F112 was found to convert demethylsuberosin into marmesin with a very high affinity. This atypical cyclization reaction represents a key step within the polyphenol biosynthesis pathway. CYP76F112 evolutionary patterns suggests that the marmesin synthase activity appeared recently in the Moraceae family, through a lineage-specific expansion and diversification. The characterization of CYP76F112 as the first known marmesin synthase opens new prospects for the use of the furanocoumarin pathway. It also supports the multiple acquisition of furanocoumarin in angiosperms by convergent evolution, and opens new perspectives regarding the ability of cytochromes P450 to evolve new functions related to plant adaptation to their environment.


Do variants associated with susceptibility to pancreatic cancer and type 2 diabetes reciprocally affect risk?
Although type 2 diabetes mellitus is a known risk factor for pancreatic cancer, the existence of shared genetic susceptibility is largely unknown. We evaluated whether any reported genetic risk variants of either disease found by genome-wide association studies reciprocally confer susceptibility. Data that were generated in previous genome-wide association studies (GENEVA Type 2 Diabetes; PanScan) were obtained through the National Institutes of Health database of Genotypes and Phenotypes (dbGaP). Using the PanScan datasets, we tested for association of 38 variants within 37 genomic regions known to be susceptibility factors for type 2 diabetes. We further examined whether type 2 diabetes variants predispose to pancreatic cancer risk stratified by diabetes status. Correspondingly, we examined the association of fourteen pancreatic cancer susceptibility variants within eight genomic regions in the GENEVA Type 2 Diabetes dataset. Four plausible associations of diabetes variants and pancreatic cancer risk were detected at a significance threshold of p = 0.05, and one pancreatic cancer susceptibility variant was associated with diabetes risk at threshold of p = 0.05, but none remained significant after correction for multiple comparisons. Currently identified GWAS susceptibility variants are unlikely to explain the potential shared genetic etiology between Type 2 diabetes and pancreatic cancer.


Are You Your Friends' Friend? Poor Perception of Friendship Ties Limits the Ability to Promote Behavioral Change.
Persuasion is at the core of norm creation, emergence of collective action, and solutions to 'tragedy of the commons' problems. In this paper, we show that the directionality of friendship ties affect the extent to which individuals can influence the behavior of each other. Moreover, we find that people are typically poor at perceiving the directionality of their friendship ties and that this can significantly limit their ability to engage in cooperative arrangements. This could lead to failures in establishing compatible norms, acting together, finding compromise solutions, and persuading others to act. We then suggest strategies to overcome this limitation by using two topological characteristics of the perceived friendship network. The findings of this paper have significant consequences for designing interventions that seek to harness social influence for collective action.


Induction and partial purification of bacteriophages from Desulfovibrio vulgaris (Hildenborough) and Desulfovibrio desulfuricans ATCC 13541.
Bacteriophages were induced from cultures of Desulfovibrio vulgaris NCIMB 8303 and Desulfovibrio desulfuricans ATCC 13541 by UV light. The optimum time of UV exposure was 1 min and the maximum yield of phage was obtained 9-10 h after UV treatment. The two phage preparations were compared by restriction enzyme analysis and Southern blot hybridization. The nucleic acid from both phages was cut by restriction endonucleases specific for double-stranded DNA. The phage DNAs from D. vulgaris and D. desulfuricans showed different restriction enzyme cleavage patterns. No homology was observed between a 25 kb probe from the D. vulgaris phage DNA and the phage DNA from D. desulfuricans. Protein profiles of the phages from both sources were also studied; the D. vulgaris phage contained two major bands corresponding to Mr values of 37 000 and 56 000 while the D. desulfuricans phage contained only one major band, of Mr 38 000.


Pharmacologicaltreatment of COVID-19: lights and shadows.
At the end of December 2019, a novel coronavirus, the severe acute respiratory syndrome coronavirus 2, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China and then the entire world, forcing the World Health Organization to make the assessment that the coronavirus disease (COVID-19) can be characterized as a pandemic, the first ever caused by a coronavirus. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments for COVID-19 are currently being evaluated and tested worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. The basic treatments are mainly represented by antiviral drugs, even if the evidence is not satisfactory. Among the antivirals, the most promising appears to be remdesivir. Corticosteroids and tocilizumab seem to guarantee positive results in selected patients so far, although the timing of starting therapy and the most appropriate therapeutic schemes remain to be clarified. Efficacy of the other drugs is still uncertain, and they are currently used as a cocktail of treatments in the absence of definitive guidelines. What will represent the real solution to the enormous problem taking place worldwide is the identification of a safe and effective vaccine, for which enormous efforts and investments are underway.


A comparative study of epidural catheter colonization and infection in Intensive Care Unit and wards in a Tertiary Care Public Hospital.
Infection is a potentially serious complication of epidural analgesia and with an increase in its use in wards there is a necessity to demonstrate its safety. We aimed to compare the incidence of colonization of epidural catheters retained for short duration (for 48 h) postoperative analgesia in postanesthesia care unit and wards. It was a prospective observational study done in a tertiary care teaching public hospital over a period of 2 years and included 400 patients with 200 each belonged to two groups PACU and ward. We also studied epidural tip culture pattern, skin swab culture at the entry point of the catheter, their relation to each other and whether colonization is equivalent to infection. Data were analyzed using statistical software GraphPad. Overall positive tip culture was 6% (24), of them 7% (14) were from PACU and 5% (10) were from ward (P = 0.5285). Positive skin swab culture was 38% (150), of them 20% (80) were from PACU and 18% (70) were from ward (P = 0.3526). The relation between positive tip culture and positive skin swab culture in same patients is extremely significant showing a strong linear relationship (95% confidence interval = 0.1053-0.2289). The most common microorganism isolated was Staphylococcus epidermidis. No patient had signs of local or epidural infection. There is no difference in the incidence of epidural catheter tip culture and skin swab culture of patients from the general ward and PACU. Epidural analgesia can be administered safely for 48 h in general wards without added risk of infection. The presence of positive tip culture is not a predictor of epidural space infection, and colonization is not equivalent to infection; hence, routine culture is not needed. Bacterial migration from the skin along the epidural track is the most common mode of bacterial colonization; hence, strict asepsis is necessary.


Target-dependent hormonal control of neuron size in the rat spinal nucleus of the bulbocavernosus.
The spinal nucleus of the bulbocavernosus (SNB) in the rat is a cluster of sexually dimorphic motoneurons that innervate perineal muscles. In adult male rats, the size of SNB neurons is reduced following castration, and this effect is reversed by treatment with testosterone. However, androgen receptors are present in the perineal muscles as well as in SNB neurons. Therefore, it is not clear whether the neuronal size is regulated by direct action of the hormone on SNB neurons or by a target-derived factor that may be controlled via hormonal action on the innervated muscle. To address this question, the peripheral (pudendal) nerve of SNB neurons on one side was cut and united to the grafted soleus muscle, which lacks androgen sensitivity. On the control side, the pudendal nerve was similarly cut but was allowed to reinnervate the perineal muscles. The size of SNB neurons was measured on both sides after a postoperative period of 10 weeks, during which the animal had been castrated or treated with testosterone after castration. The size of SNB neurons that had reinnervated perineal muscles was reduced following castration and enlarged by testosterone treatment. In contrast, the size of SNB neurons that had innervated the soleus muscle remained unaltered in response to testosterone manipulation. It is concluded that hormonal regulation of the size of SNB neurons in adult rats is mediated by their target muscles.


Quality Assurance. Historical perspective and critical issues.
Quality assurance in dentistry traces its roots to the experience of medicine. Emerging challenges to the traditional practice of dentistry have created a more receptive environment for the introduction of quality assurance systems. This article underscores some of the historical perspectives as well as the critical issues facing dentistry with regard to quality assurance.


[EFFECTIVENESS OF CYTOFLAVIN FOR THE CORRECTION OF COGNITIVE IMPAIRMENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS].
Authors studied the efficacy of cytoflavin in the correction of cognitive impairment in patients with type 2 diabetes mellitus and the drug influence on the level of brain-derived neurotrophic factor (BDNF) in blood serum. The results of treatment and examination of 60 patients with type 2 diabetes diagnosis have been analyzed. The majority (49-81.6%) of patients initially exhibited light (35-71.4%) and moderate (14-28.6%) cognitive impairments. All patients received standard treatment with oral antidiabetic drugs: metformin monotherapy (26 patients or 43.3%) and combined therapy (metformin + gliclazide, 34 patients or 56.6%). In addition, 30 patients (main group) received a complex metabolic drug cytoflavin daily intravenously (10 mL in 200 mL of 0.9% sodium chloride) for 10 days with transition to the tablet form in a dose of 2 tablets (with 0.6 succinic acid, 0.1 riboxin, 0:05 nicotinamide, 0.01 riboflavin) two times a day for 25 days. The control group (n = 30) consisted of patients who received only basic hypoglycemic therapy. The inclusion of cytoflavin in the scheme of complex treatment of patients with type 2 diabetes ensured a more effective correction of cognitive impairments as compared to the group receiving basic therapy. This is confirmed by the results of neuropsychological testing (MoCA test) and improved optical and spatial activity, attention, abstract thinking, and memory on the average by 14.2% compared to the value before treatment (p < 0.01) in patients of standard treatment group. Patients in the control group showed positive dynamics of same parameters amounted on the average to 7.9%. The study of BDNF in the blood serum showed a significant increase in this index over time in patients who have received cytoflavin (from 1475.13 + 421.26 pg/ml to 1839.44 + 494.78 pg/mL, p < 0.01) in contrast to the control group (1625.41 + 322.53 pg/mL to 1592.04 + 373.47 pg/mL) and revealed positive correlation between the MoCA test and BDNF level in the blood serum for optico-spatial activity (r = 0.589, p < 0.01), naming (animals) (r = 0.346, p < 0.01), attention (r = 0.401, p < 0.01), memory (r=0.595, p< 0.01) and total rating in the test (r = 0.708, p < 0.01). In addition, a negative correlation was revealed between the level of carbohydrate metabolism (HbA1c) and BDNF levels in the blood serum (r = -0.494, p < 0.01) in both groups.


Implementation of two novel schemes for patients on dialysis as a response to the COVID-19 surge in Tokyo.
The Japanese government recommended hospitalization of patients on dialysis once they tested positive because of their high COVID-19 mortality rate and definite need for periodic dialysis. However, after experiencing the Delta variant surge, strategic changes towards outpatient care for mild or asymptomatic cases, along with strengthening emergency preparedness were needed. Facing the Omicron surge, the Tokyo Metropolitan Government introduced two novel schemes: i) a temporary medical facility with a dialysis center for infected patients on hemodialysis, which started admitting patients on dialysis on January 20, 2022, to provide additional bed capacity and access to hemodialysis and ii) a transportation scheme for patients who need travel to maintenance dialysis facilities from their homes, which was introduced on February 5. The Tokyo Metropolitan Government, cooperating with some nephrology experts, announced these schemes and urged local dialysis facilities to change strategies, providing information regarding infection prevention measures and treatments in online seminars on February 3 and 7. Consequently, promoting outpatient care did not lead to an increase in the case fatality ratio (CFR) in patients on dialysis with COVID-19 in Tokyo during the first Omicron surge (January 7 to February 10, 8.2%; February 11 to March 31, 5.5%). Furthermore, after an additional online seminar on July 20, the CFR dramatically declined in the second Omicron surge (July 8 to September 8, 1.2%). Implementation of public health intervention and careful communication with local dialysis facilities were both crucial to the strategic changes. To maintain essential health services, emergency preparedness should be cultivated during regular times.


The Association between the Percentage of Female Law Enforcement Officers and Rape Report, Clearance, and Arrest Rates: A Spatiotemporal Analysis of California.
Rape is an underreported violent crime that frequently remains uncleared (open) in the legal system. Rape disproportionately affects women, with 91% of rape victim-survivors estimated to be female. However, law enforcement agencies, the entry point into the criminal justice system, are predominantly comprised of male officers. According to the theory of representative bureaucracy, groups with greater representation in a bureaucratic system are more likely to have their interests protected. This study aims to determine if California law enforcement agencies with a higher percentage of female officers are more likely to have higher rates of rape reporting, clearances, and arrests. No previous study has examined this relationship using statewide data. Crimes and Clearances, Monthly Arrest and Citation Register, and Uniform Crime Reporting data for California (2013-2016) were aggregated into 499 Law Enforcement Reporting Areas (LERA). Bayesian space-time Poisson regressions controlling for LERA demographics and crime produced scaled relative rates for three outcomes: (a) rape report rate: number of reports relative to population ages 18+; (b) rape clearance rate: number of clearances relative to reports; and (c) rape arrest rate: number of arrests for rape relative to reports. A 5% increase in the percentage of female officers within an agency was associated with a 6.2% increase in the rape report rate (ARR: 1.062, 95% credible interval (CI) [1.048, 1.077]), a 2.9% decrease in the clearance rate (ARR: 0.971 95% CI [0.950, 0.993]), and no change in the rape arrest rates (ARR: 1.010; 95% CI [0.981, 1.039]) across all LERA. Thus, increased female officer representation was associated with an increase in rape reporting rates but associated with a decrease in rape clearance rates. The theory of representative bureaucracy was only partially supported, and these relationships may not be causal. The quantity of rape reports received by an agency, employment and promotion practices of agencies, and victim-survivor's attitudes toward officer's gender should also be considered.


Could successful cryoballoon ablation of paroxysmal atrial fibrillation prevent progressive left atrial remodeling?
Radiofrequency catheter ablation of atrial fibrillation (AF) has been proved to be effective and to prevent progressive left atrial (LA) remodeling. Cryoballoon catheter ablation (CCA), using a different energy source, was developed to simplify the ablation procedure. Our hypothesis was that successful CCA can also prevent progressive LA remodeling. 36 patients selected for their first CCA because of nonvalvular paroxysmal AF had echocardiography before and 3, 6 and 12 months after CCA. LA diameters, volumes (LAV) and LA volume index (LAVI) were evaluated. LA function was assessed by: early diastolic velocities of the mitral annulus (Aa(sept), Aa(lat)), LA filling fraction (LAFF), LA emptying fraction (LAEF) and the systolic fraction of pulmonary venous flow (PVSF). Detailed left ventricular diastolic function assessment was also performed. Excluding recurrences in the first 3-month blanking period, the clinical success rate was 64%. During one-year of follow-up, recurrent atrial arrhythmia was found in 21 patients (58%). In the recurrent group at 12 months after ablation, minimal LAV (38 ± 19 to 44 ± 20 ml; p < 0.05), maximal LAV (73 ± 23 to 81 ± 24 ml; p < 0.05), LAVI (35 ± 10 to 39 ± 11 ml/m2; p = 0.01) and the maximal LA longitudinal diameter (55 ± 5 to 59 ± 6 mm; p < 0.01) had all increased. PVSF (58 ± 9 to 50 ± 10%; p = 0.01) and LAFF (36 ± 7 to 33 ± 8%; p = 0.03) had decreased. In contrast, after successful cryoballoon ablation LA size had not increased and LA function had not declined. In the recurrent group LAEF was significantly lower at baseline and at follow-up visits. In patients whose paroxysmal atrial fibrillation recurred within one year after cryoballoon catheter ablation left atrial size had increased and left atrial function had declined. In contrast, successful cryoballoon catheter ablation prevented progressive left atrial remodeling.


[A comprehensive analysis of incidence of myocardial infarction in Vladikavkaz depending on solar and geomagnetic activity].
The data on myocardial infarction morbidity in Vladikavkaz for 2007-2010 were analysed with reference to solar and geomagnetic activity. Time series of morbidity in men and women were constructed and their seasonal constituent was distinguished. It was found that the number of myocardial infarctions increases on day with enhanced geomagnetic activity especially among subjects aged 50-69 years. Regression analysis of the relationship between the number of sunspots and myocardial infarctions yielded the equation of piecewise linear regression showing that 42% of the cases were due to the changes in the number of sunspots. Medium strength negative correlation was found between the number of myocardial infarctions and the recurrence index of Bz-component of the interplanetary magnetic field. It suggests an important role of chaotic dynamics of external factors in the development of myocardial infarction.


Distribution and characterization of Listeria monocytogenes clinical isolates in Portugal, 1994-2007.
In recent years, the number of cases of listeriosis has increased worldwide. Ninety-five isolates of Listeria monocytogenes recovered from Portuguese human cases of listeriosis have been characterized by biotyping (cadmium and arsenic sensitivity), polymerase chain reaction (PCR) grouping, and by pulsed-field gel electrophoresis (PFGE) applying the enzymes AscI and ApaI. Isolates were classified into one of three PCR groups; IVb (71.6%), IIb (17.9%), and IIa (10.5%). Four biotypes were differentiated: sensitive to arsenic/cadmium (48.4%), arsenic-sensitive and cadmium-resistant (25.3%), resistant to arsenic and sensitive to cadmium (18.9%), and resistant to both heavy metals (7.4%). Combined analyses of AscI and ApaI patterns yielded a total of 58 PFGE types with five sets (G, Jb, KKa, Me, and U) of Portuguese strains, each of which were indistinguishable by PFGE typing. In the present study, it was demonstrated that there are recurrent pulsotypes and that some were the same pulsotypes linked to outbreaks in France. In addition, there are some pulsotypes spread throughout the country, while others only appear in a restricted region. This study allowed the assembly of a first large pulsotype database of Portuguese clinical strains.


Molecular Accessibility and Diffusion of Resorufin in Zeolite Crystals.
Invited for the cover of this issue is the group of Professor Bert Weckhuysen at Utrecht University. The image depicts the change in fluorescence color of a resorufin dye molecule when it is protonated and confined inside the micropores of zeolite-β. Read the full text of the article at 10.1002/chem.202302553.


Amelioration of Ischemic Brain Injury in Rats With Human Umbilical Cord Blood Stem Cells: Mechanisms of Action.
Despite the high prevalence and devastating outcome, there remain a few options for treatment of ischemic stroke. Currently available treatments are limited by a short time window for treatment and marginal efficacy when used. We have tested a human umbilical cord blood-derived stem cell line that has been shown to result in a significant reduction in stroke infarct volume as well as improved functional recovery following stroke in the rat. In the present study we address the mechanism of action and compared the therapeutic efficacy of high- versus low-passage nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs). Using the middle cerebral arterial occlusion (MCAo) model of stroke in Sprague-Dawley rats, we administered nh-UCBSC by intravenous (IV) injection 2 days following stroke induction. These human cells were injected into rats without any immune suppression, and no adverse reactions were detected. Both behavioral and histological analyses have shown that the administration of these cells reduces the infarct volume by 50% as well as improves the functional outcome of these rats following stroke for both high- and low-passaged nh-UCBSCs. Flow cytometry analysis of immune cells present in the brains of normal rats, rats with ischemic brain injury, and ischemic animals with nh-UCBSC treatment confirmed infiltration of macrophages and T cells consequent to ischemia and reduction to normal levels with nh-UCBSC treatment. Flow cytometry also revealed a restoration of normal levels of microglia in the brain following treatment. These data suggest that nh-UCBSCs may act by inhibiting immune cell migration into the brain from the periphery and possibly by inhibition of immune cell activation within the brain. nh-UCBSCs exhibit great potential for treatment of stroke, including the fact that they are associated with an increased therapeutic time window, no known ill-effects, and that they can be expanded to high numbers for, and stored for, treatment.


Cosmesis in segmental mastectomy.
The controversy about the best treatment for primary breast cancer will be settled only when properly designed clinical trials are completed. Most surgeons would rather await the results of such trials than participate in them. Prominent among the reasons for this view is the belief that an adequate cancer operation can seldom be performed with appropriate cosmetic preservation of the breast and, therefore, the trial of an unproven operation is not justified, because nothing can be gained. The poor cosmetic result is often owing to lack of experience with segmental mastectomy. From experience with 400 patients in the National Surgical Adjuvant Breast Project (NSABP) protocol has emerged an appreciation of the technical points that permit adequately wide local excision with minimal cosmetic loss. The results should stimulate both patients and surgeons to consider appropriate clinical trials for primary breast cancer surgery. This paper considers the causes of cosmetic failure and suggests the means of overcoming them.


[Transcranial magnetic stimulation].
Transcranial magnetic stimulation is a non-invasive tool for the electrical stimulation of the cerebral cortex, and for evaluation of the excitability of the motor cortex and pathways. Transcranial magnetic stimulation can be applied as single pulses of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. Single stimuli can depolarize neurons and evoke measurable effects. Series of stimuli (repetitive transcranial magnetic stimulation) can modify the excitability of the cerebral cortex at the stimulated site and also at remote areas along functional anatomical connections. TMS might provide novel insights into the pathophysiology of the neural circuitry underlying neurological and psychiatric disorders, but more work is needed to establish the role of transcranial magnetic stimulation in clinical neurology.


Handling of Ventricular Fibrillation in the Emergency Setting.
Ventricular fibrillation (VF) and sudden cardiac death (SCD) are predominantly caused by channelopathies and cardiomyopathies in youngsters and coronary heart disease in the elderly. Temporary factors, e.g., electrolyte imbalance, drug interactions, and substance abuses may play an additive role in arrhythmogenesis. Ectopic automaticity, triggered activity, and reentry mechanisms are known as important electrophysiological substrates for VF determining the antiarrhythmic therapies at the same time. Emergency need for electrical cardioversion is supported by the fact that every minute without defibrillation decreases survival rates by approximately 7%-10%. Thus, early defibrillation is an essential part of antiarrhythmic emergency management. Drug therapy has its relevance rather in the prevention of sudden cardiac death, where early recognition and treatment of the underlying disease has significant importance. Cardioprotective and antiarrhythmic effects of beta blockers in patients predisposed to sudden cardiac death were highlighted in numerous studies, hence nowadays these drugs are considered to be the cornerstones of the prevention and treatment of life-threatening ventricular arrhythmias. Nevertheless, other medical therapies have not been proven to be useful in the prevention of VF. Although amiodarone has shown positive results occasionally, this was not demonstrated to be consistent. Furthermore, the potential proarrhythmic effects of drugs may also limit their applicability. Based on these unfavorable observations we highlight the importance of arrhythmia prevention, where echocardiography, electrocardiography and laboratory testing play a significant role even in the emergency setting. In the following we provide a summary on the latest developments on cardiopulmonary resuscitation, and the evaluation and preventive treatment possibilities of patients with increased susceptibility to VF and SCD.


A glucose derivative as natural alternative to the cyclohexane-1,2-diamine ligand in the anticancer drug oxaliplatin?
Having oxaliplatin as archetype, several platinum complexes with a carbohydrate moiety resembling the cyclohexane-1,2-diamine ligand of oxaliplatin have been prepared. As leaving groups, the anionic ligands iodide, oxalate, and malonate were utilized, and for comparison purposes the chloro complex was employed. All compounds were characterized by elemental analysis, nuclear magnetic resonance spectroscopy, and electrospray mass spectrometry. The crystal structure of (SP-4-3)-diiodo(2,3-diamino-2,3-dideoxy-D-glucose-kappa(2)N,N')platinum(II) was determined by X-ray diffraction. The affinity toward dGMP was assayed by capillary electrophoresis, revealing that the chloro complex shows the highest reactivity, followed by the iodo complex. In contrast, the binding kinetics of the dicarboxylato complexes are slower, with the malonato complex being the least reactive. Reactivity to dGMP in the cell-free system correlates with cytotoxicity in two of four human cancer cell lines as determined by means of the MTT assay. In three of the four cell lines, the chloro and the malonato complex are the most and the least active of the carbohydrate-Pt complexes, respectively, with IC(50) values differing only by factors of up to 3.2. Cytotoxicity of the chloro complex is one to two orders of magnitude lower than that of oxaliplatin, but still comparable to that of carboplatin in two of the four cell lines.


[Determination of vitamin C in selected fruit and vegetable products].
A simple method was described to determine vitamin C as L-ascorbic acid (after reduction of dehydroascorbic acid by means of dithiothreitol) in fruit juices, fruit and vegetable-fruit nectars. Ascorbic acid was analyzed by RP-HPLC technique with UV detection (254 nm). The average recovery of ascorbic acid was 92-103% and limits of identification and detection were 0.003 and 0.009 mg/ml of products respectively.


Extra long imaging range swept source optical coherence tomography using re-circulation loops.
One of the main drawbacks of the swept source optical coherence tomography (SS-OCT) is its limited axial range. A novel interferometer configuration is proposed, equipped in each arm with an adjustable path length ring. By compensating the losses in the rings using semiconductor optical amplifiers, multiple paths A-scans can be obtained which when combined axially, can lead to an extremely long overall axial range. The effect of the re-circulation loops is equivalent with extending the coherence length of the swept source. In this way, the axial imaging range in SS-OCT can be pushed well beyond the limit imposed by the coherence length of the laser, to exceed in principle many centimeters.


Personal black carbon exposure influences ambulatory blood pressure: air pollution and cardiometabolic disease (AIRCMD-China) study.
Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia's megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four-hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) μg/m(3). Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17-0.89 and 0.10-0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of -0.06 (95% confidence interval, 0.62-9.60 and -0.11 to -0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution.


Effects of electroacupuncture at BL33 on detrusor smooth muscle activity in a rat model of urinary retention.
Detrusor smooth muscle (DSM) underactivity may lead to urinary retention (UR). Electroacupuncture (EA) at BL33 may be effective in improving DSM contractions. This study aimed to investigate: (1) the effect of EA at BL33; and (2) the effect of different manipulation methods at BL33 on the modulation of DSM contractions in UR rats. 30 male Sprague-Dawley rats were anaesthetised with urethane and modelled by urethral outlet obstruction. First, 2 Hz EA at BL33, SP6 and LI4 wasrandomly applied to the UR rats for 5 min to observe the immediate effects (n=10); second, manual acupuncture (MA) (n=10) and 100 Hz EA (n=10) were applied with the same programme. DSM electromyography (EMG) and cystometrogram data were evaluated. (1) 2 Hz EA at BL33 and SP6 significantly increased DSM discharging frequency (0.80±0.10 Hz, P<0.001, and 0.22±0.14 Hz, P=0.038), shortened micturation intervals (65.67±20.65 s, P=0.008, and 35.62±15.84 s, P=0.042), prolonged the duration of voiding (2.13±0.61 s, P=0.005, and 0.47±0.16 s, P=0.015), and reduced residual pressure (-0.91±0.31 mmHg, P=0.019, and -0.66±0.27 mmHg, P=0.046). EA at LI4 was not associated with any functional effects (P>0.05). Compared with SP6, EA at BL33 had greater positive effects on DSM discharging frequency, duration of discharging, and duration of voiding (all P<0.05). (2) No statistically significant differences were shown between MA, 2 Hz EA and 100 Hz EA interventions when stimulating at BL33, SP6 or LI4. EA at BL33 improved DSM contractions to a greater degree than EA at SP6 or LI4. There were no differences in effect when stimulating using 2 Hz EA, 100 Hz EA and MA.


The effect of exacerbation history on outcomes in the IMPACT trial.
IMPACT, a 52-week, randomised, double-blind trial, assessed the efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI or UMEC/VI in patients with symptomatic COPD and a history of exacerbations.Subgroup analyses assessed whether the efficacy of FF/UMEC/VI versus FF/VI or UMEC/VI and UMEC/VI versus FF/VI varies according to prior exacerbation history, and the combined effects of exacerbation history and blood eosinophil counts. Three subgroups were defined: single moderate (1 moderate/no severe; n=3056 (30%)), frequent moderate (≥2 moderate/no severe; n=4628 (45%)) and severe (≥1 severe/any moderate; n=2671 (26%)). End-points included annual on-treatment moderate/severe exacerbation rate (pre-specified), lung function and health status (both post-hoc).Moderate/severe exacerbation rates (reduction % (95% CI)) were reduced in the FF/UMEC/VI group versus FF/VI (single moderate 20% (10-29), frequent moderate 11% (2-19), severe 17% (7-26)) and versus UMEC/VI (single moderate 18% (5-29), frequent moderate 29% (21-37), severe 26% (14-35)). Moderate/severe exacerbation rates were reduced in the FF/VI group versus UMEC/VI in the frequent moderate subgroup; a numerical reduction was observed in the severe subgroup (single moderate 2% (-12-18), frequent moderate 21% (11-29), severe 11% (-3-22)). Moderate/severe exacerbation rates were lower in the FF/VI group compared with UMEC/VI in patients with higher eosinophil counts. FF/UMEC/VI improved lung function and health status versus both dual therapies irrespective of exacerbation subgroup. UMEC/VI improved lung function versus FF/VI in all subgroups.Triple therapy was more effective than dual regardless of exacerbation history, consistent with results in the intent-to-treat population. Comparisons between dual therapies were influenced by prior exacerbation history and eosinophil counts.


Weight-length relationships of wild-caught and captive Atlantic bottlenose dolphins.
Length and weight measurements were obtained on 144 Atlantic bottlenose dolphins (Tursiops truncatus). Data were compared for wild-caught dolphins (n = 124), dolphins in training (n = 34), and dolphins that had died in an emaciated condition (n = 15). The purpose of the study was to establish guidelines for use in estimating when a dolphin is over- or underweight. Regression lines were plotted to give the minimal acceptable weight for any length from 185 to 265 cm.


The Value of Activated Ion Electron Transfer Dissociation for High-Throughput Top-Down Characterization of Intact Proteins.
High-throughput top-down proteomic experiments directly identify proteoforms in complex mixtures, making high quality tandem mass spectra necessary to deeply characterize proteins with many sources of variation. Collision-based dissociation methods offer expedient data acquisition but often fail to extensively fragment proteoforms for thorough analysis. Electron-driven dissociation methods are a popular alternative approach, especially for precursor ions with high charge density. Combining infrared photoactivation concurrent with electron transfer dissociation (ETD) reactions, i.e., activated ion ETD (AI-ETD), can significantly improve ETD characterization of intact proteins, but benefits of AI-ETD have yet to be quantified in high-throughput top-down proteomics. Here, we report the first application of AI-ETD to LC-MS/MS characterization of intact proteins (<20 kDa), highlighting improved proteoform identification the method offers over higher energy-collisional dissociation (HCD), standard ETD, and ETD followed by supplemental HCD activation (EThcD). We identified 935 proteoforms from 295 proteins from human colorectal cancer cell line HCT116 using AI-ETD compared to 1014 proteoforms, 915 proteoforms, and 871 proteoforms with HCD, ETD, and EThcD, respectively. Importantly, AI-ETD outperformed each of the three other methods in MS/MS success rates and spectral quality metrics (e.g., sequence coverage achieved and proteoform characterization scores). In all, this four-method analysis offers the most extensive comparisons to date and demonstrates that AI-ETD both increases identifications over other ETD methods and improves proteoform characterization via higher sequence coverage, positioning it as a premier method for high-throughput top-down proteomics.


Differential expression of immunophilins FKBP51 and FKBP52 in the frontal cortex of HIV-infected patients with major depressive disorder.
Patients infected with human immunodeficiency virus (HIV) have a higher risk of developing major depressive disorder (MDD) than the general population. Immunophilins FKBP51 and FKBP52 are expressed in cortical neurons and regulate the function of the glucocorticoid receptor (GR). Previous reports have shown that genetic variants in the FKBP5 gene encoding FKBP51 are linked to psychiatric disorders. We sought to determine whether immunophilins are upregulated in HIV infection. To determine whether FKBP52 and FKBP51 are associated with MDD and/or HIV, we compared protein and gene expression in autopsy tissues from the frontal cortical gray matter. The study cases were divided into five groups: control, MDD, MDD with psychosis, HIV(+), and HIV(+) with MDD. Gene expression and protein levels were determined by real-time PCR and Western blot analysis of fresh frozen tissues. Genotyping of previously published alleles of the FKBP5 gene was also performed. We found correlation of upregulation of both immunophilins in the HIV-infected groups. In the HIV(+) population with MDD, FKBP4 expression is significantly higher while FKBP5 is more variable. After analyzing the FKBP5 gene for single nucleotide polymorphisms, we found that rs3800373 CC genotype is more frequent in the MDD and MDD/Psychosis groups. We hypothesized that the levels of FKBP51, as modulator of the nuclear translocation of GR, would be lower in MDD. Instead, an increase in FKBP51 at both the transcript (FKBP5) and protein level correlated with MDD. Increased FKBP4 expression of correlated to HIV(+)MDD but not to HIV without MDD.


Patient controlled analgesia with remifentanil versus epidural analgesia in labour: randomised multicentre equivalence trial.
To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. Multicentre randomised controlled equivalence trial. 15 hospitals in the Netherlands. Women with an intermediate to high obstetric risk with an intention to deliver vaginally. To exclude a clinically relevant difference in satisfaction with pain relief of more than 10%, we needed to include 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation to correct for missing data. Before the onset of active labour consenting women were randomised to a pain relief strategy with patient controlled remifentanil or epidural analgesia if they requested pain relief during labour. Primary outcome was satisfaction with pain relief, measured hourly on a visual analogue scale and expressed as area under the curve (AUC), thus providing a time weighted measure of total satisfaction with pain relief. A higher AUC represents higher satisfaction with pain relief. Secondary outcomes were pain intensity scores, mode of delivery, and maternal and neonatal outcomes. Analysis was done by intention to treat. The study was defined as an equivalence study for the primary outcome. 1414 women were randomised, of whom 709 were allocated to patient controlled remifentanil and 705 to epidural analgesia. Baseline characteristics were comparable. Pain relief was ultimately used in 65% (447/687) in the remifentanil group and 52% (347/671) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48). Cross over occurred in 7% (45/687) and 8% (51/671) of women, respectively. Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The area under the curve for total satisfaction with pain relief was 30.9 in the remifentanil group versus 33.7 in the epidural analgesia group (mean difference -2.8, 95% confidence interval -6.9 to 1.3). For who actually received pain relief the area under the curve for satisfaction with pain relief after the start of pain relief was 25.6 in the remifentanil group versus 36.1 in the epidural analgesia group (mean difference -10.4, -13.9 to -7.0). The rate of caesarean section was 15% in both groups. Oxygen saturation was significantly lower (SpO2 <92%) in women who used remifentanil (relative risk 1.5, 1.4 to 1.7). Maternal and neonatal outcomes were comparable between both groups. In women in labour, patient controlled analgesia with remifentanil is not equivalent to epidural analgesia with respect to scores on satisfaction with pain relief. Satisfaction with pain relief was significantly higher in women who were allocated to and received epidural analgesia. Netherlands Trial Register NTR2551.


Xanthomonas oryzae pathovars: model pathogens of a model crop.
SUMMARY Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola cause bacterial blight and bacterial leaf streak of rice (Oryza sativa), which constrain production of this staple crop in much of Asia and parts of Africa. Tremendous progress has been made in characterizing the diseases and breeding for resistance. X. oryzae pv. oryzae causes bacterial blight by invading the vascular tissue, while X. oryzae pv. oryzicola causes bacterial leaf streak by colonizing the parenchyma. In rice there are 29 major genes for resistance to bacterial blight, but so far only a few quantitative resistance loci for bacterial leaf streak. Over 30 races of X. oryzae pv. oryzae have been reported. Both pathogens exhibit genetic variation among isolates. Mechanisms of pathogenesis and resistance have begun to be elucidated. Members of the AvrBs3/PthA family of transcription activator-like effectors play a major role in the virulence of X. oryzae pv. oryzae and possibly X. oryzae pv. oryzicola. Cloning of six rice resistance genes for bacterial blight and one from maize effective against bacterial leaf streak has uncovered a diversity of structure and function, some shared by genes involved in defence in animals. This article reviews research that spans a century. It also presents a perspective on challenges for sustainable control, and opportunities that interactions of X. oryzae pathovars with rice present as models for understanding fundamental aspects of bacterial pathogenesis of plants and plant disease resistance, as well as other aspects of plant and microbial biology, with implications also for animal innate immunity.


Performance evaluation of occupational therapy students: a reliability study.
The Performance Evaluation of Occupational Therapy Students (PEOTS) is an instrument designed to evaluate the clinical competence of occupational therapy students. The purpose of this study was to carry out a preliminary evaluation of the inter-rater and test-retest reliability of the PEOTS. Thirteen occupational therapy students, completed a one week placement at one of four facilities. Two occupational therapists supervised each student and evaluated performance using the PEOTS on day three and day five of this placement. The results indicated that the instrument has good inter-rater reliability. Test-retest reliability was difficult to evaluate since learning was a confounding factor. These preliminary findings support the use of the PEOTS as an evaluation tool. Further research, however, is needed to establish test-retest reliability and internal consistency of the PEOTS.


Factors Driving Changes in the Design, Implementation, and Scaling-Up of the Contracting of Health Services in Rural Cambodia, 1997-2015.
Abstract-Contracting approaches have been used in various forms to improve the delivery of public health services in low- and middle-income countries. Cambodia has embarked on a public-sector reform that includes a model of internal contracting of health care through the Ministry of Health, supported by incentive payments for staff and facilities. Contracting for health care in Cambodia has evolved through three phases during 1997-2015, each with particular design features, arrangements, and structures; different levels of involvement of local and international stakeholders; and modifications based on evidence from operational research. Based on a review of published and gray literature and interviews with 29 local and international key informants, we identify national ownership, financial sustainability, and the need to strengthen service delivery institutions as the major forces that have shaped contracting in Cambodia, culminating in the move to internal contracting arrangements for public health care delivery. There remains a need to strengthen contracting governance arrangements.


[Glaucoma dynamics in patients who followed monitoring and treatment instructions and in those who didn't].
Clinical course of different stages of primary open-angle glaucoma (POAG) is studied in 216 patients (432 eyes) who followed monitoring and treatment instructions during 13 years and in those who didn't. In patients who did not follow recommendations glaucoma progression was found in 99,4% of patients with initial disease, in 48,7% of cases with advanced stage and in 50% of patients with the end stage of the disease. Patients who followed recommendations of general ophthalmologists and glaucomatologists showed stable course of glaucoma process in 1 patient (0,6%) with initial stage, in 51,3% of patients with advanced stage and in 50% of patients with the end stage of the disease.


"Some sort of fantasy land": A qualitative investigation of appropriate prescribing in cancer care.
Increasing the appropriateness of prescribing has long been a focus of government, non-government, and professional organizations. Progress towards this is made difficult by the fact appropriate prescribing remains inconsistently defined and is the subject of ongoing intense disagreement. In this study, we attempted to understand why this is the case within the context of oncology and haematology. We performed a qualitative empirical analysis of semi-structured interviews with 16 Australian oncologists and haematologists. We found that oncologists framed appropriate prescribing in terms of the following inter-related, and at times opposed, values: civic mindedness, hope and compassion, realism, and virtue in motivation. These values cannot be ranked a priori, and therefore, any definition of appropriate prescribing must be aligned with what communities want from their health system. When one value is privileged over another in any specific context, a compelling argument must be provided to justify the choice. In an era of shared decision making, patient rights, and high-cost medicines, we need to reassess what we mean by appropriate prescribing in cancer care.


Long-term iron deficiency: Tracing changes in the proteome of different pea (Pisum sativum L.) cultivars.
Iron deficiency (-Fe) is one of the major problems in crop production. Dicots, like pea (Pisum sativum L.), are Strategy I plants, which induce a group of specific enzymes such as Fe(III)-chelate reductase (FRO), Fe responsive transporter (IRT) and H(+)-ATPase (HA) at the root plasma membrane under -Fe. Different species and cultivars have been shown to react diversely to -Fe. Furthermore, different kinds of experimental set-ups for -Fe have to be distinguished: i) short-term vs. long-term, ii) constant vs. acute alteration and iii) buffered vs. unbuffered systems. The presented work compares the effects of constant long-term -Fe in an unbuffered system on roots of four different pea cultivars in a timely manner (12, 19 and 25days). To differentiate the effects of -Fe and plant development, control plants (+Fe) were analyzed in comparison to -Fe plants. Besides physiological measurements, an integrative study was conducted using a comprehensive proteome analysis. Proteins, related to stress adaptation (e.g. HSP), reactive oxygen species related proteins and proteins of the mitochondrial electron transport were identified to be changed in their abundance. Regulations and possible functions of identified proteins are discussed. Pea (Pisum sativum L.) belongs to the legume family (Fabaceae) and is an important crop plant due to high Fe, starch and protein contents. According to FAOSTAT data (September 2015), world production of the garden pea quadrupled from 1970 to 2012. Since the initial studies by Gregor Mendel, the garden pea became the most-characterized legume and has been used in numerous investigations in plant biochemistry and physiology, but is not well represented in the "omics"-related fields. A major limitation in pea production is the Fe availability from soils. Adaption mechanisms to Fe deficiency vary between species, and even cultivars have been shown to react diversely. A label-free proteomic approach, in combination with physiological measurements, was chosen to observe four different pea cultivars for 5 to 25days. Physiological and proteome data showed that cultivar Blauwschokker and Vroege were more susceptible to -Fe than cultivar Kelvedon (highly efficient) and GftR (semi-efficient). Proteomic data hint that the adaptation process to long-term -Fe takes place between days 19 and 25. Results show that adaptation processes of efficient cultivars are able to postpone secondary negative effects of long-term -Fe, possibly by stabilizing the protein metabolic processing and the mitochondrial electron transport components. This maintains the cellular energy proliferation, keeps ROS production low and postpones the mitochondrial cell death signal.


Direct excitation of inhibitory interneurons by extracellular ATP mediated by P2Y1 receptors in the hippocampal slice.
ATP is an important cell-to-cell signaling molecule mediating the interactions between astrocytes and neurons in the CNS. In the hippocampal slices, ATP suppresses excitatory transmission mostly through activation of adenosine A1 receptors, because the ectoenzyme activity for the extracellular breakdown of ATP to adenosine is high in slice preparations in contrast to culture environments. Because the hippocampus is also rich in the expression of P2 receptors activated specifically by ATP, we examined whether ATP modulates neuronal excitability in the acute slice preparations independently of adenosine receptors. Although ATP decreased the frequency of spontaneously occurring EPSCs in the CA3 pyramidal neurons through activation of adenosine A1 receptors, ATP concurrently increased the frequency of IPSCs in a manner dependent on action potential generation. This effect was mediated by P2Y1 receptors because (1) 2-methylthio-ATP (2meSATP) was the most potent agonist, (2) 2'-deoxy-N6-methyladenosine-3',5'-bisphosphate diammonium (MRS2179) abolished this effect, and (3) this increase in IPSC frequency was not observed in the transgenic mice lacking P2Y1 receptor proteins. Application of 2meSATP elicited MRS2179-sensitive time- and voltage-dependent inward currents in the interneurons, which depolarized the cell to firing threshold. Also, it increased [Ca2+]i in both astrocytes and interneurons, but, unlike the former effect, the latter was entirely dependent on Ca2+ entry. Thus, in hippocampal slices, in addition to activating A1 receptors of the excitatory terminals after being converted to adenosine, ATP activates P2Y1 receptors in the interneurons, which is linked to activation of unidentified excitatory conductance, through mechanisms distinct from those in the astrocytes.


Biochemical, molecular, and genetic analyses of the acetone carboxylases from Xanthobacter autotrophicus strain Py2 and Rhodobacter capsulatus strain B10.
Acetone carboxylase is the key enzyme of bacterial acetone metabolism, catalyzing the condensation of acetone and CO(2) to form acetoacetate. In this study, the acetone carboxylase of the purple nonsulfur photosynthetic bacterium Rhodobacter capsulatus was purified to homogeneity and compared to that of Xanthobacter autotrophicus strain Py2, the only other organism from which an acetone carboxylase has been purified. The biochemical properties of the enzymes were virtually indistinguishable, with identical subunit compositions (alpha(2)beta(2)gamma(2) multimers of 85-, 78-, and 20-kDa subunits), reaction stoichiometries (CH(3)COCH(3) + CO(2) + ATP-->CH(3)COCH(2)COO(-) + H(+) + AMP + 2P(i)), and kinetic properties (K(m) for acetone, 8 microM; k(cat) = 45 min(-1)). Both enzymes were expressed to high levels (17 to 25% of soluble protein) in cells grown with acetone as the carbon source but were not present at detectable levels in cells grown with other carbon sources. The genes encoding the acetone carboxylase subunits were identified by transposon mutagenesis of X. autotrophicus and sequence analysis of the R. capsulatus genome and were found to be clustered in similar operons consisting of the genes acxA (beta subunit), acxB (alpha subunit), and acxC (gamma subunit). Transposon mutagenesis of X. autotrophicus revealed a requirement of sigma(54) and a sigma(54)-dependent transcriptional activator (AcxR) for acetone-dependent growth and acetone carboxylase gene expression. A potential sigma(54)-dependent promoter 122 bp upstream of X. autotrophicus acxABC was identified. An AcxR gene homolog was identified 127 bp upstream of acxA in R. capsulatus, but this activator lacked key features of sigma(54)-dependent activators, and the associated acxABC lacked an apparent sigma(54)-dependent promoter, suggesting that sigma(54) is not required for expression of acxABC in R. capsulatus. These studies reveal a conserved strategy of ATP-dependent acetone carboxylation and the involvement of transcriptional enhancers in acetone carboxylase gene expression in gram-negative acetone-utilizing bacteria.


Physical, psychological and ethical issues in caring for individuals with genetic skin disease.
Some forms of genetic skin disease are highly prevalent and others are exceedingly rare, but collectively, genetic skin disorders (or genodermatoses) are often poorly understood. The purpose of this article, therefore, is to increase nurses' awareness and understanding of some of the physical, psychological, social, and ethical issues facing patients with inherited skin disorders. This article offers an overview of genetic skin diseases; highlights the complexity and prevalence of the genodermatoses; describes inheritance patterns, genetics, and treatment for six genodermatoses; and reviews some of the ethical, privacy, technological, and resource issues nurses should consider when caring for patients with genetic skin disorders. Because genodermatoses are found in all age groups, across all populations, and within all healthcare settings, nurses are uniquely positioned to address the educational and healthcare needs of patients and families with inherited skin disorders. Over the past two decades, genetics has evolved from a niche specialty into general practice. To ensure that patients and their families receive appropriate services and resources, nurses must have a working knowledge of genetic concepts. This article reinforces key genetic concepts while discussing many of the issues and concerns important to caring for patients with genetic skin disease.


Nutrition and breast cancer risk by age 50: a population-based case-control study in Germany.
Diet is recognized to play a role in the occurrence of breast cancer; however, the data are inconsistent. The goal of this study was to determine the influence of dietary factors on breast cancer risk among women up to 50 yr of age in a German population. A population-based case-control study was conducted including 706 cases and 1,381 controls. In addition to a risk factor questionnaire, a subgroup of 355 cases and 838 controls completed a food frequency questionnaire. Breast cancer risk was inversely associated with vegetable consumption (P for trend = 0.034). The odds ratio for the fourth quartile of vegetable intake compared with the first quartile was 0.64 (95% confidence interval = 0.43-0.96). Breast cancer risk increased with a higher consumption of red meat (P for trend = 0.016); women with the highest consumption level had an 85% elevated breast cancer risk compared with the lowest quartile (95% confidence interval = 1.23-2.78). When only premenopausal women were considered, the protective effect of vegetable intake and the positive association with meat intake were even stronger. These results are compatible with the international recommendations for a breast cancer preventive diet and suggest that the favorable effect of a diet high in vegetables and low in red meat, especially beef, may be stronger in premenopausal women.


Reductions in circulating anabolic hormones induced by sustained sleep deprivation in rats.
The main systemic disorders resulting from prolonged sleep deprivation in laboratory animals are a negative energy balance, low circulating thyroid hormones, and host defense impairments. Low thyroid hormones previously have been found caused by altered regulation at the level of the hypothalamus with possible pituitary involvement. The present studies investigated the effects of sleep deprivation on other major anabolic hormonal systems. Plasma growth hormone (GH) concentrations and major secretory bursts were characterized. Insulin-like growth factor I (IGF-I) was evaluated as an integrative marker of peripheral GH effector activity. Prolactin (PRL) was assessed by basal concentrations and by stimulating the pituitary with exogenous thyrotropin-releasing hormone. Leptin was studied for its linkage to metabolic signs of sleep loss and its correspondence to altered neuroendocrine regulation in other disease states. Last, plasma corticosterone was measured to investigate the degree of hypothalamic-pituitary-adrenal activation. Sleep deprivation was produced by the disk-over-water method, a well-established means of selective deprivation of sleep and noninterference with normal waking behaviors. Hormone concentrations were determined in sham comparisons and at intervals during baseline and experimental periods lasting at least 15 days in partially and totally sleep-deprived rats. The results indicate that high-amplitude pulses of GH were nearly abolished and that concentrations of GH, IGF-I, PRL, and leptin all were suppressed by sleep deprivation. Corticosterone concentration was relatively unaffected. Features of these results, such as low GH and low IGF-I, indicate failed negative feedback and point to hypothalamic mechanisms as containing the foci responsible for peripheral signs.


In vitro myelopoiesis stimulated by rapid medium exchange and supplementation with hematopoietic growth factors.
We studied the effect of the combination of rapid culture medium exchange with the addition of the human hematopoietic growth factors interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (Epo) on the proliferation and differentiation of human long-term bone marrow cultures (LTBMCs). Individually and in combinations, IL-3, GM-CSF, and Epo were added to the culture medium of LTBMCs that were maintained with 50% medium volume exchange per day. The combination of IL-3 + GM-CSF + Epo generated the most prolific cultures with an order of magnitude increase in nonadherent cell production from weeks 2 through 8 in culture as compared with unsupplemented controls. Under these conditions, the cultures produced as many cells as were inoculated every 2 weeks and led to a greater than 2.5-fold expansion in terms of the number of nonadherent cells produced over a 6- to 8-week period. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. The rapid medium exchange combined with the addition of human hematopoietic CSFs significantly enhances the proliferation and differentiation of LTBMCs. These results indicate that addition of combinations of hematopoietic CSFs, together with a rapid medium exchange rate, can provide culture conditions that are suitable for the expansion of the progenitor cell pool and perhaps for the increased survival of hematopoietic stem cells in culture. Although these culture conditions still fall short of full reconstitution of functional human bone marrow, they provide an improved approach to hematopoietic cell culture that may permit the expansion and manipulation of progenitor cells in vitro.


Effect of ether inhalation by adrenalectomized pregnant rats on the adrenal corticosterone concentration in norma, decapitated, and encephalectomized fetuses.
The influence of decapitation or encephalectomy (total removal of the brain leaving the pituitary in place) on the adrenal corticosterone concentration of the 20-day-old rat fetus has been studied in normal pregnant rats, in adrenalectomized pregnant rats, and in adrenalectomized pregnant rats subjected to the stress conditions of inhalation of ether for 40 min. Decapitation or encephalectomy of the fetus always results in a drop in adrenal corticosterone concentration within 4 h which is prevented in 15 min by injecting 3.2 mU of hog ACTH into the decapitated fetus. In mothers adrenalectomized in order to avoid a negative feedback reaction of maternal corticosteroids on the fetal pituitary-adrenal system, ether inhalation causes an important rise in adrenal corticosterone concentration in normal fetuses but not in decapitated or encephalectomized ones. Thus ether, which crosses the placental barrier, is a stressor agent for the fetal rat.


The subcellular localization of ubiquinone in human neutrophils.
Ubiquinone-10 has recently been proposed as a component of the microbicidal oxidase system of neutrophil leukocytes [Crawford & Schneider (1982) J. Biol. Chem. 257, 6662-6668]. We have determined the subcellular localization of ubiquinone and could detect it only in the mitochondrial fractions. It was not enriched in phagolysosomes which were enriched in O2-. generating activity and cytochrome b-245. It is proposed that ubiquinone is unlikely to play a direct role in the electron transport chain located in the plasma membrane which functions to produce microbicidal oxygen radicals.


Antimicrobial susceptibility testing: special needs for fastidious organisms and difficult-to-detect resistance mechanisms.
Clinical microbiology laboratories are faced with the challenge of accurately detecting emerging antibiotic resistance among a number of bacterial pathogens. In recent years, vancomycin resistance among enterococci has become prevalent, as has penicillin resistance and multidrug resistance in pneumococci. More recently, strains of methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin have been encountered. In addition, molecular techniques have demonstrated that there are still problems detecting methicillin resistance in staphylococci, especially in coagulase-negative species. Among members of the family Enterobacteriaceae, mutated beta-lactamase enzymes may confer difficult-to-detect resistance to later-generation penicillins and cephalosporins. Anaerobic bacteria are no longer entirely predictable in their susceptibility to agents that might be selected for empiric therapy. Therefore, clinical microbiology laboratories may not be able to rely on a single susceptibility testing method or system to detect all those emerging resistant or fastidious organisms. For reliable detection, laboratories may need to employ conventional, quantitative susceptibility testing methods or use specially developed, single concentration agar screening tests for some resistant species. Certain of these screening tests are highly specific, while others may require additional confirmatory testing for definitive results. Therefore, laboratories must retain the versatility to apply several different approaches to detect resistance in both common and infrequently encountered bacterial pathogens.