Therapeutic approaches in the prevention of cardiovascular disease in metabolic syndrome and in patients with type 2 diabetes.
The metabolic syndrome is commonly encountered in the United States. It has been estimated from a survey conducted nearly a decade ago that one in four American adults fulfill the criteria for the metabolic syndrome. As obesity has become more common, the prevalence of type 2 diabetes has increased, and these trends can be expected to translate into more cardiovascular disease in future years. The high cardiovascular risk that accompanies the metabolic syndrome and type 2 diabetes mandates comprehensive and aggressive preventive care. This article reviews evidence that treatments directed at the individual components of the metabolic syndrome will delay the progression to type 2 diabetes and will reduce the incidence of cardiovascular disease. In overweight individuals with the metabolic syndrome, the onset of type 2 diabetes can be delayed by therapeutic lifestyle changes (weight loss and exercise), insulin sensitizers (metformin, troglitazone), angiotensin converting enzyme inhibitors (captopril, fosinopril, ramipril), and angiotensin receptor blockers (losartan, candesartan). Lipid altering therapies (statins, fibrates, and niacin) are especially efficacious for reducing cardiovascular events in metabolic syndrome and type 2 diabetes patients. An aggressive multifactorial approach to cardiovascular risk factor modification facilitates a delay in the onset of type 2 diabetes and cardiovascular events among individuals with the metabolic syndrome.


Bidirectional promoters are the major source of gene activation-associated non-coding RNAs in mammals.
The majority of non-coding RNAs (ncRNAs) involved in mRNA metabolism in mammals have been believed to downregulate the corresponding mRNA expression level in a pre- or post-transcriptional manner by forming short or long ncRNA-mRNA duplex structures. Information on non-duplex-forming long ncRNAs is now also rapidly accumulating. To examine the directional properties of transcription at the whole-genome level, we performed directional RNA-seq analysis of mouse and chimpanzee tissue samples. We found that there is only about 1% of the genome where both the top and bottom strands are utilized for transcription, suggesting that RNA-RNA duplexes are not abundantly formed. Focusing on transcription start sites (TSSs) of protein-coding genes revealed that a significant fraction of them contain switching-points that separate antisense- and sense-biased transcription, suggesting that head-to-head transcription is more prevalent than previously thought. More than 90% of head-to-head type promoters contain CpG islands. Moreover, CCG and CGG repeats are significantly enriched in the upstream regions and downstream regions, respectively, of TSSs located in head-to-head type promoters. Genes with tissue-specific promoter-associated ncRNAs (pancRNAs) show a positive correlation between the expression of their pancRNA and mRNA, which is in accord with the proposed role of pancRNA in facultative gene activation, whereas genes with constitutive expression generally lack pancRNAs. We propose that single-stranded ncRNA resulting from head-to-head transcription at GC-rich sequences regulates tissue-specific gene expression.


Functional non-coding RNAs derived from the flavivirus 3' untranslated region.
Flaviviruses are single-stranded positive sense RNA enveloped viruses. The flavivirus genus includes important human pathogens such as dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Murray Valley encephalitis virus (MVEV). In addition to the viral proteins and viral genomic RNA, flaviviruses produce at least two functional non-coding RNAs derived from the 3' untranslated region (3'UTR), the subgenomic flavivirus RNA (sfRNA) and a putative WNV miRNA (KUN-miR-1). In this review we summarize published data from studies with WNV, YFV, DENV, JEV, and MVEV on sfRNA production following incomplete degradation of the viral genomic RNA by the cellular 5'-3' exoribonuclease 1 (XRN1), RNA structural elements involved in stalling XRN1 to generate sfRNA, and functions of sfRNA in modulating cellular mRNA decay and RNAi pathways as well as in modulating anti-viral type I interferon response. In addition, we also summarize data on the mechanisms of biogenesis of 3'UTR-derived KUN-miR-1 and its function in WNV replication in mosquito host, along with recent findings on a discovery of a second potential flaviviral miRNA vsRNA5, derived from the 3'UTR of DENV. This review thus summarizes the known mechanisms of generation and the functions of flaviviral 3'UTR-derived non-coding RNAs.


Two mid-pregnancy interventions to increase the initiation and duration of breastfeeding: a randomized controlled trial.
Despite high levels of breastfeeding initiation in Australia, only 46 percent of women are still breastfeeding (exclusively or partially) 6 months later, with marked differences between social groups. This study aimed to determine the influence of mid-pregnancy breastfeeding education on the proportions of women breastfeeding at hospital discharge, and on the duration of breastfeeding. A randomized controlled trial to compare two strategies for increasing the initiation and duration of breastfeeding was conducted, in which 981 primiparas who attended a public, tertiary women's hospital in Melbourne, Australia, were randomized to one of two interventions or to standard care (327 in each group). The interventions were a 1.5-hour class on practical aspects of breastfeeding using a previously tested tool (Practical Skills), and two 1-hour classes exploring family and community attitudes toward, and experiences of, breastfeeding (Attitudes). Both interventions took place in interactive small groups when women were in mid-pregnancy. Breastfeeding initiation was ascertained by interview 2 to 4 days after birth, and breastfeeding duration was assessed by telephone interview 6 months after birth. Neither intervention increased breastfeeding initiation or duration compared with standard care. Rates at initiation were 97 percent (296/306) for the Practical Skills intervention, 95 percent (291/308) for the Attitudes intervention, and 96 percent (297/310) for standard care. Rates at 6 months were, respectively, 55 percent (162/297), 50 percent (146/293), and 54 percent (162/299). In settings where breastfeeding initiation is already high, neither study intervention could be recommended as an effective strategy to increase breastfeeding initiation or duration.


Exploratory Investigation of Infrared Thermography for Measuring Gorilla Emotional Responses to Interactions with Familiar Humans.
Interactions between zoo professionals and animals occur regularly and are believed to be enriching for animals. Little empirical information exists on how animals perceive these interactions, and particularly how the interactions affect the emotional states of animals. Infrared thermography (IRT) has shown some promise in the assessment of emotions in a variety of species, but further research is needed to determine if this method is useful in a zoo setting. We conducted a pilot study to determine if IRT is a valid measure of the emotional responses to routine interactions (positive reinforcement training and cognitive tasks, compared to a control condition) with familiar humans on three western lowland gorillas at the Detroit Zoo. We measured nasal temperatures associated with emotional change using IRT. To examine the validity of the IRT data, we collected saliva samples for hormone analysis before and after each condition, in addition to behavioral data during the interactions and control condition. Decreases in nasal temperatures for two gorillas and an increase in the third indicate that arousal changed consistently within individuals following the interactions but not the control condition. Pre-post cortisol levels and oxytocin concentrations decreased for all conditions, but the decreases seen did not differ among the conditions. The gorillas were highly engaged in the interactions, and two produced more grumble vocalizations during the human-animal interactions (HAIs) compared to the control condition. Additionally, the gorillas performed self-directed behaviors more often during the control condition, also suggesting HAIs were not a negative experience. In summary, we were able to measure changes in arousal using IRT, but we were unable to determine the emotional valence of these changes based on the additional indicators employed. Additionally, the inconsistency across these measures precluded firm conclusions about either the validity of IRT for measuring emotion in this context or how the interactions impacted these gorillas. These findings highlight the challenges of using IRT to measure emotional states in non-human animals, and we discuss further steps necessary to apply this method in future studies.


Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia.
Ghrelin is a strong physiologic growth hormone secretagogue that exhibits endocrine and non-endocrine actions. In this study, ghrelin expression in humans and rats was evaluated throughout development of normal and hypoplastic lungs associated with congenital diaphragmatic hernia (CDH). Additionally, the effect of antenatal treatment with ghrelin in the nitrofen-induced CDH rat model was tested. In normal lungs, ghrelin was expressed in the primitive epithelium at early stages of development and decreased in levels of expression with gestational age. In hypoplastic lungs ghrelin was overexpressed in both human and rat CDH fetuses when compared with controls. Exogenous administration of ghrelin to nitrofen-treated dams led to an attenuation of pulmonary hypoplasia of CDH pups. Furthermore, the growth hormone, secretagogue receptor (GHSR1a), could not be amplified from human or rat fetal lungs by RT-PCR. In conclusion, of all the lungs studied so far, the fetal lung is one of the first to express ghrelin during development and might be considered a new source of circulating fetal ghrelin. Overexpression of ghrelin in hypoplastic lungs and the effect of exogenous administration of ghrelin to nitrofen-treated dams strongly suggest a role for ghrelin in mechanisms involved in attenuation of fetal lung hypoplasia, most likely through a GHSR1a-independent pathway.


The 5S and 5.8S ribosomal RNA sequences of Tetrahymena thermophila and T. pyriformis.
The nucleotide sequences of the 5S rRNAs of Tetrahymena thermophila and two strains of T. pyriformis have been determined to be identical. The 5.8S rRNA sequences have also been determined; these sequences correct several errors in an earlier report. The 5.8S rRNAs of the two species differ at a single position. The sequencing results indicate that the species are of recent common ancestry. Molecular evidence that has been interpreted in the past as suggestive of an ancient divergence has been reviewed and found to be consistent with a T. pyriformis complex radiation beginning approximately 30-40 million years ago.


Membrane nanodomains: contribution of curvature and interaction with proteins and cytoskeleton.
The understanding of lipid membranes and their organization has undergone significant development with better techniques and therefore more resolved experiments. Many new factors and organizing principles have been discovered, and interplay between these factors is expected to result in rich functional behaviours. The major factors regulating the lateral membrane heterogeneity, apart from the well-studied phase separation, are cytoskeleton pinning, clustering of lipids and curvature. These factors are effective means to create membrane domains that provide rich biological functionality. We review the recent advances and concepts of membrane heterogeneity organization by curvature, cytoskeleton and clustering proteins.


A new method of DNA sequencing using deoxynucleoside alpha-thiotriphosphates.
A new procedure for determining DNA nucleotide sequences is reported. In the first step of the method, four DNAs, each separately substituted with a different deoxynucleoside phosphorothioate in place of the corresponding monophosphate, are prepared by template-directed polymerization catalyzed by DNA polymerase. In the second step, these DNAs are subjected to stringent exonuclease III treatment, which produces only fragments terminating with a phosphorothioate internucleotide linkage. These can then be separated by standard gel electrophoresis techniques and the sequence can be read directly as in presently used sequencing methods.


Macular corneal dystrophy. Lack of keratan sulfate in serum and cornea.
An ELISA assay using a monoclonal antibody (ET-4-A-4) that recognizes a sulfated carbohydrate epitope in both keratan sulfate type I (corneal) and type II (skeletal) was employed to quantify keratan sulfate in serum and corneal tissue from patients with macular corneal dystrophy (MCD). This assay disclosed significant quantities of keratan sulfate in the serum in 45 healthy individuals (251 +/- 78 ng/ml), and in 66 patients with various corneal diseases (273 +/- 101 ng/ml). In contrast keratan sulfate was not detected (less than 2 ng/ml) in the serum of 16 patients with histopathologically confirmed MCD. Keratan sulfate was also detected in extracts of normal corneas and corneal tissue with a variety of pathologic conditions, but was virtually absent in corneal tissue from five patients with MCD. In corneas with MCD the chondroitin sulfate/keratan sulfate ratio was considerably higher than that of all normal and pathologic corneas studied. Since keratan sulfate in the serum appears to be derived predominantly from the normal turnover of cartilage these studies strongly suggest that the defect in keratan sulfate synthesis in MCD is not restricted to corneal cells and that MCD is one manifestation of a systemic disorder of keratan sulfate. The cartilage changes, however, do not have clinical significance. Moreover, since keratan sulfate can be detected in the blood of newborns it should be possible to diagnose MCD prior to corneal opacification.


Serum albumin: accuracy and clinical use.
Albumin is the major plasma protein and its determination is used for the prognostic assessment of several diseases. Clinical guidelines call for monitoring of serum albumin with specific target cut-offs that are independent of the assay used. This requires accurate and equivalent results among different commercially available methods (i.e., result standardization) through a consistent definition and application of a reference measurement system. This should be associated with the definition of measurement uncertainty goals based on medical relevance of serum albumin to make results reliable for patient management. In this paper, we show that, in the current situation, if one applies analytical goals for serum albumin measurement derived from its biologic variation, the uncertainty budget derived from each step of the albumin traceability chain is probably too high to fulfil established quality levels for albumin measurement and to guarantee the accuracy needed for clinical usefulness of the test. The situation is further worsened if non-specific colorimetric methods are used for albumin measurement as they represent an additional random source of uncertainty.


Engineering a de novo-designed coiled-coil heterodimerization domain off the rapid detection, purification and characterization of recombinantly expressed peptides and proteins.
Using the techniques of genetic engineering and the principles of protein de novo design, we have developed a unique affinity matrix protein tag system as a rapid, convenient and sensitive method to detect, purify and characterize newly expressed recombinant peptides or proteins from cell extracts. The method utilizes two de novo-designed linear peptide sequences that can selectively dimerize to form the stable protein motif, the two-stranded alpha-helical coiled-coil. In this method, a recombinant bacterial expression vector pRLDE has been engineered so that one of the dimerization strands (E-coil) is expressed as a C-terminal fusion tag on newly expressed peptides or proteins, while the other (K-coil) is either biotin-labeled for detection in a Western blot-type format or immobilized on an insoluble silica support for selective dimerization affinity chromatography. Recombinantly expressed peptides from Escherichia coli containing the dimerization tag have been produced, detected and purified using this method. The recombinant peptides were easily and clearly identified using the biotin-labeled coil, while the single-step affinity purification results indicated the purity of the affinity purified expressed peptides to be > 95%, as assessed by reversed-phase chromatography. The stability of the dimerization domain also allows for the purified peptide to be left attached to the matrix, thus creating a new peptide-bound column that can be used to study peptide-protein or peptide-ligand interactions. Therefore this system offers a new alternative to existing peptide or protein fusion tags and demonstrates the utility of a de novo-designed system.


Triazine dyes, a new class of affinity labels for nucleotide-dependent enzymes.
A number of reactive dichlorotriazine dyes specifically and irreversibly inactivate pig heart lactate dehydrogenase, yeast glucose 6-phosphate dehydrogenase and yeast hexokinase at sites competitive with NAD+, NADP+, and ATP respectively. Monochlorotriazine dyes, including Cibacron Blue F3G-A, do not inactivate lactate dehydrogenase but display high affinity and thus inhibit the inactivation by dichlorotriazine dyes. These data are interpreted in terms of the ability of nucleotide-binding enzymes to bind polysulphonated aromatic chromophores.


Maintenance of cell fates and regulation of the histone variant H3.3 by TLK kinase in Caenorhabditis elegans.
Cell-fate maintenance is important to preserve the variety of cell types that are essential for the formation and function of tissues. We previously showed that the acetylated histone-binding protein BET-1 maintains cell fate by recruiting the histone variant H2A.z. Here, we report that Caenorhabditis elegans TLK-1 and the histone H3 chaperone CAF1 prevent the accumulation of histone variant H3.3. In addition, TLK-1 and CAF1 maintain cell fate by repressing ectopic expression of transcription factors that induce cell-fate specification. Genetic analyses suggested that TLK-1 and BET-1 act in parallel pathways. In tlk-1 mutants, the loss of SIN-3, which promotes histone acetylation, suppressed a defect in cell-fate maintenance in a manner dependent on MYST family histone acetyltransferase MYS-2 and BET-1. sin-3 mutation also suppressed abnormal H3.3 incorporation. Thus, we propose a hypothesis that the regulation and interaction of histone variants play crucial roles in cell-fate maintenance through the regulation of selector genes.


Shape invariance and a universal form for the Gouy phase.
It is shown that Hermite-Gaussian beams, Laguerre-Gaussian beams, and certain linear combinations thereof are the only finite-energy coherent beams that propagate, on free propagation, in a shape-invariant manner. All shape-invariant beams have Gouy phase of the universal c arctan(z/zR) form, with quantized values for the prefactor c. It is also shown that, as limiting cases, even two- and three-dimensional nondiffracting beams belong to this class when the Rayleigh distance goes to infinity. The results are deduced from the transport-of-intensity equations, by elementary means as well as by use of the Iwasawa decomposition. A pivotal role in the analysis is the finding that the only possible change in the phase front of a shape-invariant beam from one transverse plane to another is quadratic.


Inflation targeting: A time-frequency causal investigation.
The enduring discourse regarding the effectiveness of interest rate policy in mitigating inflation within developing economies is characterized by the interplay of structural and supply-side determinants. Moreover, extant academic literature fails to resolve the direction of causality between inflation and interest rates. Nevertheless, the prevalent adoption of interest rate-based monetary policies in numerous developing economies raises a fundamental inquiry: What motivates central banks in these nations to consistently espouse this strategy? To address this inquiry, our study leverages wavelet transformation to dissect interest rate and inflation data across a spectrum of frequency scales. This innovative methodology paves the way for a meticulous exploration of the intricate causal interplay between these pivotal macroeconomic variables for twenty-two developing economies using monthly data from 1992 to 2022. Traditional literature on causality tends to focus on short- and long-run timescales, yet our study posits that numerous uncharted time and frequency scales exist between these extremes. These intermediate scales may wield substantial influence over the causal relationship and its direction. Our research thus extends the boundaries of existing causality literature and presents fresh insights into the complexities of monetary policy in developing economies. Traditional wisdom suggests that central banks should raise interest rates to combat inflation. However, our study uncovers a contrasting reality in developing economies. It demonstrates a positive causal link between the policy rate and inflation, where an increase in the central bank's interest rates leads to an upsurge in price levels. Paradoxically, in response to escalating prices, the central bank continues to heighten the policy rate, thereby perpetuating this cyclical pattern. Given this observed positive causal relationship in developing economies, central banks must explore structural and supply-side factors to break this cycle and regain control over inflation.


Apocryphal FADS2 activity promotes fatty acid diversification in cancer.
Canonical fatty acid metabolism describes specific enzyme-substrate interactions that result in products with well-defined chain lengths, degree(s), and positions of unsaturation. Deep profiling of lipids across a range of prostate cancer cell lines reveals a variety of fatty acids with unusual site(s) of unsaturation that are not described by canonical pathways. The structure and abundance of these unusual lipids correlate with changes in desaturase expression and are strong indicators of cellular phenotype. Gene silencing and stable isotope tracing demonstrate that direct Δ6 and Δ8 desaturation of 14:0 (myristic), 16:0 (palmitic), and 18:0 (stearic) acids by FADS2 generate new families of unsaturated fatty acids (including n-8, n-10, and n-12) that have rarely-if ever-been reported in human-derived cells. Isomer-resolved lipidomics reveals the selective incorporation of these unusual fatty acids into complex structural lipids and identifies their presence in cancer tissues, indicating functional roles in membrane structure and signaling.


Effects of ethanol and tobacco on time judgment.
To determine the effects of the joint administration of tobacco and ethanol on short-interval time production and to search for differences between the ascending, the peak and the descending limb of the blood alcohol curve, two groups of 6 male subjects were tested on intervals of 1.5, 4.0 and 9.0 sec. Ethanol at 0.06% and 0.08% blood alcohol significantly lengthened the scores and one cigarette produced lower scores. The relationship between level of blood alcohol and time scores reversed in the latter part of the test session. The results are discussed in terms of effects of drugs on arousal systems.


HA14-1 is able to reconstitute the impaired mitochondrial pathway of apoptosis in renal cell carcinoma cell lines.
Renal cell carcinomas (RCCs) exhibit a marked resistance towards apoptosis. Although most apoptotic stimuli converge at the level of the mitochondria, little is known about the mitochondrial apoptosis pathway in renal cell carcinomas. The aim of the present study, therefore, was to investigate the functionality of the mitochondrial apoptosis pathway in renal cell carcinoma cell lines by exposure to TRAIL, etoposide, HA14-1 and betulinic acid activating the mitochondria by different mechanisms. Sensitivity to TRAIL-induced apoptosis correlated with cleavage of the initiator caspase-8, but the mitochondrial apoptosis pathway was not induced. Similarly, etoposide and betulinic acid could not induce mitochondrial damage. In contrast, HA14-1 was able to activate mitochondrial apoptosis, thereby demonstrating functionally inducible signalling pathways downstream of the mitochondria. The intactness of the pathways upstream of the mitochondria was shown by pretreatment of TRAIL-sensitive cell lines with HA14-1, which could reconstitute TRAIL-induced mitochondrial damage and resulted in a synergistic apoptosis induction. Our results demonstrate that the apoptotic pathways upstream and downstream of the mitochondria are intact and inducible in renal cell carcinoma cell lines. However, resistance towards mitochondrial apoptosis is located on the level of the mitochondria themselves.


Prevalence and duration of asymptomatic Clostridium difficile carriage among healthy subjects in Pittsburgh, Pennsylvania.
Previous studies suggested that 7 to 15% of healthy adults are colonized with toxigenic Clostridium difficile. To investigate the epidemiology, genetic diversity, and duration of C. difficile colonization in asymptomatic persons, we recruited healthy adults from the general population in Allegheny County, Pennsylvania. Participants provided epidemiological and dietary intake data and submitted stool specimens. The presence of C. difficile in stool specimens was determined by anaerobic culture. Stool specimens yielding C. difficile underwent nucleic acid testing of the tcdA gene segment with a commercial assay; tcdC genotyping was performed on C. difficile isolates. Subjects positive for C. difficile by toxigenic anaerobic culture were asked to submit additional specimens. One hundred six (81%) of 130 subjects submitted specimens, and 7 (6.6%) of those subjects were colonized with C. difficile. Seven distinct tcdC genotypes were observed among the 7 C. difficile-colonized individuals, including tcdC genotype 20, which has been found in uncooked ground pork in this region. Two (33%) out of 6 C. difficile-colonized subjects who submitted additional specimens tested positive for identical C. difficile strains on successive occasions, 1 month apart. The prevalence of C. difficile carriage in this healthy cohort is concordant with prior estimates. C. difficile-colonized individuals may be important reservoirs for C. difficile and may falsely test positive for infections due to C. difficile when evaluated for community-acquired diarrhea caused by other enteric pathogens.


Blood fatty acid composition in relation to allergy in children aged 2-9 years: results from the European IDEFICS study.
Blood polyunsaturated fatty acids (PUFA) are involved in allergy development, but the etiological role of n-6 and n-3 PUFA is still controversial. A European multicenter study of children (IDEFICS) provided the opportunity to explore the cross-sectional association between fatty acids (FA) and allergy. Blood FA levels were measured in 2600 children aged 2-9 years and were recorded as the percentage of weight of all FA detected. Logistic regression of allergy status on FA components was adjusted for age, sex, country, body mass index, family history of allergic disease, breast-feeding, and number of siblings. The results were given as odds ratios (OR) for current vs no allergy ever and an increase in FA by 1 s.d. Overall, higher proportions of n-6 PUFA were associated with higher odds of allergy (OR=1.21 (1.05, 1.40)). Monounsaturated FA (MUFA) were associated with reduced risk for allergy (OR=0.75 (0.65, 0.87)), whereas saturated FA did not differ by allergy status. The strongest associations were observed in children <4 years old, with ORs of allergy given as 1.62 (1.15, 2.29) for n-3 PUFA and 0.63 (0.42, 0.95) for MUFA. With regard to individual FA, these associations were independently observed for docosapentaenoic acid (22:5 n-3) and oleic acid (18:1 n-9). Both PUFA subtypes were positively associated with allergy in an age-dependent manner, whereas MUFA was associated with less allergy. The observation of high proportions of n-3 PUFA in allergic children younger than 4 years might help to understand the nature of early onset of atopic disease.


Cardiac resynchronization therapy in patients with mild heart failure: a systematic review and meta-analysis.
Cardiac resynchronization therapy (CRT) reduces symptoms and improves survival in patients with advanced heart failure (New York Heart Association (NYHA) functional class III-IV), reduced ejection fraction, and wide QRS complex. Whether CRT has the same benefit also in asymptomatic or mildly symptomatic heart failure patients is controversial. Our objective is to summarize the available evidence on the effects of CRT in asymptomatic or mildly symptomatic (NYHA I-II) heart failure patients. We searched major web databases for randomized controlled trials of CRT in patients with mild heart failure (NYHA functional class I-II). Data regarding all-cause mortality, heart failure events, left ventricular (LV) volumes and ejection fraction, and worsening of NYHA functional class were extracted. We identified five trials (CONTAK-CD, MIRACLE ICD-II, REVERSE, MADIT-CRT, and RAFT) that enrolled 4,213 patients (91% with NYHA II functional class). Primary analysis excluded the CONTAK-CD, which was not specifically conducted on patients with mild heart failure. At pooled analysis, CRT decreased mortality (odds ratio (OR), 0.78 [95% confidence interval (CI)], 0.63 to 0.97; p = 0.024) and heart failure events (OR, 0.63 [95% CI, 0.52 to 0.76], p < 0.001), induced a significant LV reverse remodeling (weighted mean difference (WMD) of LV ejection fraction [Formula: see text], p = 0.015 and WMD of LV end-systolic volume index [Formula: see text], p < 0.001) and prevented the progression of heart failure symptoms (OR for worsening of NYHA functional class = 0.54 [95% CI, 0.31 to 0.93], p = 0.026). Inclusion of the CONTAK-CD did not change the results. Among patients with mild (NYHA II) heart failure, CRT reduces mortality and the risk of heart failure events, induces a favorable LV reverse remodeling and slows the progression of heart failure symptoms.


Enhancement of cytokine-driven NK cell IFN-γ production after vaccination of HCMV infected Africans.
Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine-induced responses, we studied NK-cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure. In contrast to populations with lower prevalence of HCMV infection, no significant enhancement of NK-cell responses (IFN-γ, CD107a, CD25) occurred after in vitro re-stimulation of post-vaccination NK cells with TIV or DTPiP antigens compared to pre-vaccination baseline cells. However, both vaccinations resulted in higher frequencies of NK cells producing IFN-γ in response to exogenous IL-12 with IL-18, which persisted for up to 6 months. Enhanced cytokine responsiveness was restricted to less differentiated NK cells, with increased frequencies of IFN-γ+ cells observed within CD56bright CD57- , CD56dim CD57- NKG2C- and CD56dim CD57- NKG2C+ NK-cell subsets. These data suggest a common mechanism whereby different vaccines enhance NK cell IFN-γ function in HCMV infected donors and raise the potential for further exploitation of NK cell "pre-activation" to improve vaccine effectiveness.


Frequencies of specific antibody-producing cells for sheep red blood cells and for phosphorylcholine in human tonsillar B lymphocytes transformed by Epstein-Barr virus.
The frequencies of transformed B cells and of transformed specific antibody-producing cells in human tonsillar lymphocytes infected with Epstein-Barr virus (EBV) were determined by limiting dilution analyses. The latter was corrected by the former and the frequencies of specific antibody-producing cells in EBV-transformed B cell populations were obtained. The frequencies of specific B cells for sheep red blood cells were calculated to be one in 500 to 2,000 EBV-transformed tonsillar B cells obtained from four donors, while those of specific B cells for a hapten, phosphorylcholine, were one in 700 to 5,000. The method may be useful to define the repertoire of specificities in the human B cell populations.


Transcriptome analysis reveals the defense mechanism of cotton against Verticillium dahliae in the presence of the biocontrol fungus Chaetomium globosum CEF-082.
Verticillium wilt of cotton is a serious soil-borne disease that causes a substantial reduction in cotton yields. A previous study showed that the endophytic fungus Chaetomium globosum CEF-082 could control Verticillium wilt of cotton, and induce a defense response in cotton plants. However, the comprehensive molecular mechanism governing this response is not yet clear. To study the signalling mechanism induced by CEF-082, the transcriptome of cotton seedlings pretreated with CEF-082 was sequenced. The results revealed 5638 DEGs at 24 h post inoculation with CEF-082, and 2921 and 2153 DEGs at 12 and 48 h post inoculation with Verticillium dahliae, respectively. At 24 h post inoculation with CEF-082, KEGG enrichment analysis indicated that the DEGs were enriched mainly in the plant-pathogen interaction, MAPK signalling pathway-plant, flavonoid biosynthesis, and phenylpropanoid biosynthesis pathways. There were 1209 DEGs specifically induced only in cotton plants inoculated with V. dahliae in the presence of the biocontrol fungus CEF-082, and not when cotton plants were only inoculated with V. dahliae. GO analysis revealed that these DEGs were enriched mainly in the following terms: ROS metabolic process, H2O2 metabolic process, defense response, superoxide dismutase activity, and antioxidant activity. Moreover, many genes, such as ERF, CNGC, FLS2, MYB, GST and CML, that regulate crucial points in defense-related pathways were identified and may contribute to V. dahliae resistance in cotton. These results provide a basis for understanding the molecular mechanism by which the biocontrol fungus CEF-082 increases the resistance of cotton to Verticillium wilt. The results of this study showed that CEF-082 could regulate multiple metabolic pathways in cotton. After treatment with V. dahliae, the defense response of cotton plants preinoculated with CEF-082 was strengthened.


Review of Bruton tyrosine kinase inhibitors for the treatment of relapsed or refractory mantle cell lymphoma.
Mantle cell lymphoma (mcl) is a rare subtype of aggressive B-cell non-Hodgkin lymphoma that remains incurable with standard therapy. Patients typically require multiple lines of therapy, and those with relapsed or refractory (r/r) disease have a very poor prognosis. The Bruton tyrosine kinase (btk) inhibitor ibrutinib has proven to be an effective agent for patients with r/r mcl. Although usually well tolerated, ibrutinib can be associated with unique toxicities, requiring discontinuation in some patients. Effective and well-tolerated alternatives to ibrutinib for patients with r/r mcl are therefore needed. Novel btk inhibitors such as acalabrutinib, zanubrutinib, and tirabrutinib are designed to improve on the safety and efficacy of first-generation btk inhibitors such as ibrutinib. Data from single-arm clinical trials suggest that, compared with ibrutinib, second-generation btk inhibitors have comparable efficacy and might have a more favourable toxicity profile. Those newer btk inhibitors might therefore provide a viable treatment option for patients with r/r mcl.


Tumor-infiltrating lymphocyte response in cutaneous melanoma in the elderly predicts clinical outcomes.
Tumor-infiltrating lymphocytes (TILs) and regression are manifestations of the host immune response to tumor, but their influence on outcome remains undefined. There is a paucity of data on the elderly who represent a growing proportion of melanoma patients. The aim of this study was to evaluate the influence of TILs and regression as an indirect measure of immunity on outcome in elderly patients with melanoma. From a prospective database, we identified 250 consecutive cutaneous melanoma patients aged at least 65 years at the time of diagnosis. Data were verified by record review. Within the primary melanoma, a brisk TIL response was present in 66 (31%), nonbrisk TILs in 36 (17%), and absent in 111 (52%). The presence of a brisk infiltrate conferred a three-fold increased risk of sentinel lymph node (SLN) metastasis (P=0.02). Despite this, nonbrisk or absent TILs were associated with a five-fold increased risk of recurrence (P=0.0001). In multivariate analysis, nonbrisk or absent TILs were independently associated with recurrence (P<0.0001), diminished 5-year disease-free survival (76 vs. 91%, P=0.0006), and 5-year melanoma-specific survival (82 vs. 95%, P=0.0008). Regression was not an independent predictor of SLN metastasis, disease-free survival, or melanoma-specific survival. Our study demonstrates that an active antitumor immune response exists in elderly melanoma patients that, paradoxically, predicts both SLN metastasis and improved melanoma-specific outcomes. Further investigation to characterize this lymphocytic infiltrate and to confirm its clinical significance as a predictor of nodal status, patient outcome, and response to immunotherapy in elderly melanoma patients appears warranted.


Preventing L5-S1 discitis associated with sacrocolpopexy.
To further characterize the anatomy of the fifth lumbar to first sacral (L5-S1) disc space and to provide anatomic landmarks that can be used to predict the locations of the disc, sacral promontory, and surrounding structures during sacrocolpopexy. The lumbosacral anatomy was examined in 25 female cadavers and 100 computed tomography (CT) studies. Measurements were obtained using the midpoint of the sacral promontory as a reference. Data were analyzed using Pearson χ, unpaired Student's t test, and analysis of covariance. The average height of the L5-S1 disc was 1.8±0.3 cm (range 1.3-2.8 cm) in cadavers and 1.4±0.4 cm (0.3-2.3) on CT (P<.001). The average angle of descent between the anterior surfaces of L5 and S1 was 60.5±9 degrees (39.5-80.5 degrees) in cadavers and 65.3±8 degrees (42.6-88.6 degrees) on CT (P=.016). The average shortest distance between the S1 foramina was 3.4±0.4 cm in cadavers and 3.0±0.4 cm on CT (P<.001). The average height of the first sacral vertebra (S1) was 3.0±0.2 cm in cadavers and 3.0±0.3 on CT (P=.269). In the supine position, the most prominent structure in the presacral space is the L5-S1 disc, which extends approximately 1.5 cm cephalad to the "true" sacral promontory. During sacrocolpopexy, awareness of a 60-degree average drop between the anterior surfaces of L5 and S1 vertebra should assist with intraoperative localization of the sacral promontory and avoidance of the L5-S1 disc. The first sacral nerve can be expected approximately 3 cm from the upper surface of the sacrum and 1.5 cm from the midline. II.


[Protective effect of soyasaponins on acute liver injury induced by D-galactosamine and lipopolysaccharide in mice].
To investigate the protective effect of soyasaponins on acute liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in mice. The mice were randomly divided into five groups: the normal control, the model group, the silymarin (positive control) group, and soyasaponins high and low-dose groups. They were administered with drugs once every day for 7 days. At the end of the experiment, GalN and LPS were injected intraperitoneally to all of the groups except for the normal group to establish the acute liver injury model. The pathological changes were detected with hematoxylin & eosin (HE) staining, tumor necrosis factor-alpha (TNF-alpha) was detected by ELISA method, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and the activation of Caspase-3 and Caspase-8 were detected by the colorimetric method. Soyasaponins could reduce the activities of serum ALT and AST, the acute hepatic injury induced by GalN/LPS, serum TNF-alpha level, hepatic NO and MDA contents, and the Caspase-3 and Caspase-8 activations of liver tissues, and increase the hepatic CAT, GPx, GST and GSH levels. Soyasaponins shows the protective effect on acute liver injury induced by GalN and LPS in mice, which may be related to its antioxidative ability and anti-liver apoptosis.


Thermodynamic study of the complexation of protactinium(V) with diethylenetriaminepentaacetic acid.
The complex formation of protactinium(V) with DTPA was studied at different temperatures (25-50 °C) and ionic strengths (0.1-1 M) with the element at tracer scale. Irrespective of the temperature and ionic strength studied, only one neutral complex with (1:1) stoichiometry was identified from solvent extraction and capillary electrophoresis coupled to ICP-MS (CE-ICP-MS) experiments. Density Functional Theory (DFT) calculations revealed that two complexes can be considered: Pa(DTPA) and PaO(H2DTPA). The associated formation constants were determined from solvent extraction data at different ionic strengths and temperatures and then extrapolated to zero ionic strength by SIT methodology. These constants are valid, regardless of complex form, Pa(DTPA) or PaO(H2DTPA). The standard thermodynamic data determined with these extrapolated constants revealed a very stable complex formed energetically by an endothermic contribution which is counter balanced by a strong entropic contribution. Both, the positive enthalpy and entropy energy terms suggest the formation of an inner sphere complex.


Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma.
Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.


[Late results of cranioplasty using explants in children].
The work is based on the analysis of 101 clinical cases in 91 of which children were subjected to cranioplasty in different periods after operation for craniocerebral injury, which terminated in the formation of a bone defect. In 5 children cranioplasty was conducted because the bone in the area of the linear fracture had resorbed, and in another 5 children it was carried out as a final stage of operation for anterior craniocerebral herniations. The children's age ranged from 3 months to 16 years. The late results of treatment were studied in 79 of 101 patients in follow-up periods of 12 months to 25 years, in 31 of them in periods of 10 to 25 years after cranioplasty. Cranioplasty must be undertaken in children as early as possible. Primary and early cranioplasty are conductive to the prevention of the formation of a meningocerebral cicatrix and a coarse adhesive process in the meninges and brain matter and are more effective than late cranioplasty.


Thiol-ene Michael-type formation of gelatin/poly(ethylene glycol) biomatrices for three-dimensional mesenchymal stromal/stem cell administration to cutaneous wounds.
Mesenchymal stromal/stem cells (MSCs) are considered promising cellular therapeutics in the fields of tissue engineering and regenerative medicine. MSCs secrete high concentrations of immunomodulatory cytokines and growth factors, which exert paracrine effects on infiltrating immune and resident cells in the wound microenvironment that could favorably promote healing after acute injury. However, better spatial delivery and improved retention at the site of injury are two factors that could improve the clinical application of MSCs. In this study, we utilized thiol-ene Michael-type addition for rapid encapsulation of MSCs within a gelatin/poly(ethylene glycol) biomatrix. This biomatrix was also applied as a provisional dressing to full thickness wounds in Sprague-Dawley rats. The three-way interaction of MSCs, gelatin/poly(ethylene glycol) biomatrices, and host immune cells and adjacent resident cells in the wound microenvironment favorably modulated wound progression and host response. In this model we observed attenuated immune cell infiltration, lack of foreign giant cell (FBGC) formation, accelerated wound closure and re-epithelialization, as well as enhanced neovascularization and granulation tissue formation by 7 days. The MSC entrapped in the gelatin/poly(ethylene glycol) biomatrix localized cell presentation adjacent to the wound microenvironment and thus mediated the early resolution of inflammatory events and facilitated the proliferative phases in wound healing.


Unusual Evolution of Cephalopod Tryptophan Indole-Lyases.
Tryptophan indole-lyase (TIL), a pyridoxal-5-phosphate-dependent enzyme, catalyzes the hydrolysis of L-tryptophan (L-Trp) to indole and ammonium pyruvate. TIL is widely distributed among bacteria and bacterial TILs consist of a D2-symmetric homotetramer. On the other hand, TIL genes are also present in several metazoans. Cephalopods have two TILs, TILα and TILβ, which are believed to be derived from a gene duplication that occurred before octopus and squid diverged. However, both TILα and TILβ individually contain disruptive amino acid substitutions for TIL activity, and neither was active when expressed alone. When TILα and TILβ were coexpressed, however, they formed a heterotetramer that exhibited low TIL activity. The loss of TIL activity of the heterotetramer following site-directed mutagenesis strongly suggests that the active heterotetramer contains the TILα/TILβ heterodimer. Metazoan TILs generally have lower kcat values for L-Trp than those of bacterial TILs, but such low TIL activity may be rather suitable for metazoan physiology, where L-Trp is in high demand. Therefore, reduced activity may have been a less likely target for purifying selection in the evolution of cephalopod TILs. Meanwhile, the unusual evolution of cephalopod TILs may indicate the difficulty of post-gene duplication evolution of enzymes with catalytic sites contributed by multiple subunits, such as TIL.


Complex aortic valve surgery for endocarditis using the beating-heart technique.
: Surgical outcomes of aortic valve surgery for endocarditis are poor. Postoperative deterioration of left ventricular (LV) function may contribute to this process. To enhance preservation of myocardial function during aortic valve surgery, we have used a beating-heart technique of myocardial protection without cardioplegic arrest. The aim of this article is to report our initial clinical experience with this technique. : We identified 30 consecutive patients with endocarditis who underwent aortic valve repair (one patient) or replacement using either a mechanical prosthesis (four patients) or a biologic prosthesis (25 patients) with beating-heart technique. There were 22 men and eight women (mean age 52.8 ± 16.1 years). There were one elective, 22 urgent/emergent, and seven "salvage" operations. Two patients had preoperative stroke, five respiratory failure, three renal failure, 12 congestive heart failure, eight septic shock, and one previous coronary artery bypass grafting. The etiology of the infection was identified in 15 patients (50%). Ten patients had severe, seven moderate, and four mild aortic insufficiency. All patients had vegetations, four had annular abscesses, and two had intracardiac fistulas. : Eight patients (26.6%) had redo procedures. Concomitant procedures included aortic and mitral valve procedure (14 patients), tricuspid valve procedure (two patients), and coronary artery bypass grafting (one patient). Aortic annular reconstruction was required in four patients (13.2%). Total CPB time was 125 ± 67 minutes. Intra-aortic balloon pump was needed in one patient. Two patients (6.6%) had a stroke unrelated to air embolism. Mean follow-up was 7.9 ± 12 months. Early mortality (30 days) was 13.3% (four patients), and late mortality was 10% (three patients). Total mortality was 18% in urgent/emergent cases, and 42% in salvage operations. There was no statistical difference between preoperative and postoperative echocardiographic values of LV function (ejection fraction and fractional shortening). LV end-diastolic dimension decreased postoperatively (P = 0.03), whereas LV end-systolic dimension and left atrial size were unchanged. : Our study did not show improved survival benefits of beating-heart aortic valve surgery compared with historical series in which conventional myocardial protection was used. However, our findings suggest that beating-heart technique is an alternative strategy of myocardial protection that may contribute to preservation of LV function in patients undergoing complex operations for aortic valve endocarditis.


Organization of the gymnotiform fish pallium in relation to learning and memory: I. Cytoarchitectonics and cellular morphology.
The present article examines the anatomical organization of the dorsal telencephalon of two gymnotiform fish: Gymnotus sp. and Apteronotus leptorhynchus. These electric fish use elaborate electrical displays for agonistic and sexual communication. Our study emphasizes mainly pallial divisions: dorsolateral (DL), dorsodorsal (DD), and dorsocentral (DC), previously implicated in social learning dependent on electric signals. We found that the pallial cytoarchitectonics of gymnotiformes are similar to those reported for the commonly studied goldfish, except that DC is larger and better differentiated in gymnotiformes. We identified a new telencephalic region (Dx), located between DL and DC, and describe the morphological and some biochemical properties of its neurons. Most neurons in DL, DD, and DC are glutamatergic with spiny dendrites. However, the size of these cells as well as the orientation and extent of their dendrites vary systematically across these regions. In addition, both DD and DL contained numerous small GABAergic interneurons as well as well-developed GABAergic plexuses. One important and novel observation is that the dendrites of the spiny neurons within all three regions remain confined to their respective territories. We confirm that DL and DC express very high levels of NMDA receptor subunits as well as CaMKIIα, a key downstream effector of this receptor. In contrast, this enzyme is nearly absent in DD, while NMDA receptors are robustly expressed, suggesting different rules for synaptic plasticity across these regions. Remarkably, GABAergic pallial neurons do not express CaMKIIα, in agreement with previously reported results in the cortex of rats.


Tuberculosis in Sudan: a study of Mycobacterium tuberculosis strain genotype and susceptibility to anti-tuberculosis drugs.
Sudan is a large country with a diverse population and history of civil conflict. Poverty levels are high with a gross national income per capita of less than two thousand dollars. The country has a high burden of tuberculosis (TB) with an estimated 50,000 incident cases during 2009, when the estimated prevalence was 209 cases per 100,000 of the population. Few studies have been undertaken on TB in Sudan and the prevalence of drug resistant disease is not known. In this study Mycobacterium tuberculosis isolates from 235 patients attending three treatment centers in Sudan were screened for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by spoligotyping. Demographic details of patients were recorded using a structured questionnaire. Statistical analyses were conducted to examine the associations between drug resistance with risk ratios computed for a set of risk factors (gender, age, case status--new or relapse, geographic origin of the patient, spoligotype, number of people per room, marital status and type of housing). Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95% CI: 14,34) of previously treated patients. Drug resistance was associated with previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB. Resistance was also associated with the geographic region of origin of the patient, being most frequently observed in patients from the Northern region and least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: < 0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR-TB. The major genotype observed was of the Central Asia spoligotype family (CAS1_Delhi), representing 49% of the 232 isolates examined. We conclude that emergence of drug resistant tuberculosis has the potential to be a serious public health problem in Sudan and that strengthened tuberculosis control and improved monitoring of therapy is needed. Further surveillance is required to fully ascertain the extent of the problem.


How to diagnose spondyloarthritis early? Accuracy of peripheral enthesitis detection by power Doppler ultrasonography.
Early diagnosis of spondyloarthritis (SpA) is sometimes difficult owing to the lack of reliable diagnostic criteria. The objective of this study was to determine the diagnostic accuracy of detecting enthesitis by power Doppler ultrasonography (PDUS) in patients with suspected SpA. A prospective single-centre cohort study was performed in patients with symptoms suggestive of SpA (inflammatory back pain, arthritis, enthesitis or dactylitis, HLAB27+ uveitis) who underwent clinical examination, pelvic x-ray, MRI of lumbar spine/sacroiliac joints, HLA-B typing and other tests judged useful for diagnosis. Blinded PDUS examination of seven sites of enthesitis was performed at baseline. The gold standard was the diagnosis made by the referring rheumatologist according to the development of symptoms and findings, blinded to PDUS results, during routine follow-up for up to 2 years. Between November 2002 and October 2004, 118 patients were included in the study. After 2 years a definite diagnosis was retained for 99 patients (51 SpA and 48 non-SpA). PDUS detection of at least one vascularised enthesis provided good predictive value for diagnosing SpA (sensitivity 76.5%; specificity 81.3%; positive likelihood ratio 4.1; OR 14.1; p<0.0001). Vascularised enthesitis detected by PDUS and Amor's criteria were the only independent contributors to a diagnosis of SpA in multivariate logistic regression (c-index=0.87). Alternatively, CART analysis resulted in a highly sensitive and specific diagnostic tree by combining PDUS with Amor's criteria. PDUS appears to be a valuable first-line diagnostic tool to confirm a diagnosis of SpA.


Pulmonary fibrotic response to inhalation of ZnO nanoparticles and toluene co-exposure through directed flow nose only exposure chamber.
The increasing use of Zinc Oxide nanoparticles (ZnONPs) in paint industry is not supplemented with adequate toxicology data. This report focuses on the fibrogenic toxicity caused due to co-exposure of ZnONPs and toluene in male Wistar rats, exposed for 28 days, through directed flow nose only exposure chamber. The rats were grouped as air control, toluene control (200 ppm), zinc oxide control (10 mg/m(3)), low dose co-exposed (5 mg/m(3) ZnO and 200 ppm of toluene) and high dose co-exposed (10 mg/m(3) of ZnO and 200 ppm of toluene). Our study demonstrates that co-exposure of ZnONPs and toluene (as in paint industry), even at their respective permissible exposure level (5 mg/m(3) for ZnO and 200 ppm for toluene) have the potential to produce a progressive inflammatory and fibrotic response in the alveolar tissues of the lungs. We observed a significant increase in inflammatory markers in BAL fluid and elevated malondialdehyde (MDA) levels with lower levels of intracellular reduced glutathione (GSH) in lungs of rats of co-exposed group. Significant increase in the levels of pro-inflammatory mediators (IL-6, Ikβα, Cox-II, p-NF-κB) in lung tissues also indicated pulmonary damage. To best of our knowledge this is the first study which highlights the toxicity of co-exposed ZnO NPs and toluene.


Sperm parameters and testicular volumes in Saguinus mystax.
Adult male Saguinus mystax tamarins were evaluated for sperm parameters and testicular volumes. Sperm concentrations average 195.5 X 10(6)/cc with 41.7% motile sperm. Semen specimens were classified as normal, relative to sperm morphology, when 95% or more of the sperm in the specimen had normal morphology; 76% of the animals evaluated had normal semen specimens using this criterion. Testicular volumes averaged 726.9 mm3. A total of 50 infants were sired by 16 of these males during the period covered by this report.


Relationships among food label use, motivation, and dietary quality.
Nutrition information on packaged foods supplies information that aids consumers in meeting the recommendations put forth in the US Dietary Guidelines for Americans such as reducing intake of solid fats and added sugars. It is important to understand how food label use is related to dietary intake. However, prior work is based only on self-reported use of food labels, making it unclear if subjective assessments are biased toward motivational influences. We assessed food label use using both self-reported and objective measures, the stage of change, and dietary quality in a sample of 392 stratified by income. Self-reported food label use was assessed using a questionnaire. Objective use was assessed using a mock shopping task in which participants viewed food labels and decided which foods to purchase. Eye movements were monitored to assess attention to nutrition information on the food labels. Individuals paid attention to nutrition information when selecting foods to buy. Self-reported and objective measures of label use showed some overlap with each other (r=0.29, p<0.001), and both predicted dietary quality (p<0.001 for both). The stage of change diminished the predictive power of subjective (p<0.09), but not objective (p<0.01), food label use. These data show both self-reported and objective measures of food label use are positively associated with dietary quality. However, self-reported measures appear to capture a greater motivational component of food label use than do more objective measures.


Commentary: Embracing innovation is necessary to improve assessment and care for individuals with ASD: a reflection on Kanne and Bishop (2020).
This commentary is offered in response to Kanne and Bishop (2020) who urge caution in adopting new devices and processes for ASD assessment and advocate that that comprehensive, expert-driven, diagnostic models for ASD remain essential to maintain quality standards. While we agree that there is a critical shortage in current care, we propose that developing suites of tools and innovative approaches for screening, risk-classification, formal diagnosis, and rich assessment of abilities and challenges may be of great value to families and necessary to improve current systems of care. As well, the evaluation of 'assessment quality' should take into consideration both content and process, with a focus on achieving meaningful outcomes and optimizing family experience.


Encapsulated nitrate replacing soybean meal changes in vitro ruminal fermentation and methane production in diets differing in concentrate to forage ratio.
The objective of this study was to evaluate the effects of using encapsulated nitrate product (ENP) replacing soybean meal in diets differing in concentrate to forage ratio on ruminal fermentation and methane production in vitro using a semi-automatic gas production technique. Eight treatments were used in a randomized complete design with a 2 × 4 factorial arrangement: two diet (20C:80F and 80C:20F concentrate to forage ratio) and four levels of ENP addition (0%, 1.5%, 3.0%, and 4.5% of DM) replacing soybean meal. There was a diet × ENP interaction (p = 0.02) for methane production. According to ENP addition, diets with 80C:20F showed more intense reduction on methane production that 20C:80F. A negative linear effect was observed for propionate production with ENP addition in diet with 80C:20F and to the relative abundance of methanogens Archaea, in both diet. The replacement of soybean meal by ENP in levels up to 3% of DM inhibited methane production due to a reduction in the methanogens community without affecting the organic matter degradability. However, ENP at 4.5% of DM level affected fiber degradability, abundance of cellulolytic bacteria, and propionic acid production, indicating that this level of inclusion is not recommended for ruminant production.


Corneal ring infiltration in contact lens wearers.
To report a case of atypical sterile ring infiltrates during wearing soft silicone hydrogel contact lens due to poor lens care. A 29-year-old woman presented with complaints of pain, redness, and morning discharge. She was wearing soft silicone hydrogel contact lens previously; her current symptoms began 1 week before presentation. On examination, best-corrected visual acuity was 20/40 in that eye. Slit-lamp examination revealed dense, ring-shaped infiltrate involving both the superficial and deep stromal layers with lucid interval to the limbus, edema of the epithelium, epithelial defect, and vascularization of the superior limbus. Cornea-specific in vivo laser confocal microscopy (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT 2-RCM, Heidelberg Engineering GmbH, Dossenheim, Germany) revealed Langerhans cells and no sign of Acanthamoeba or fungal features, using lid scraping and anti-inflammatory drops; her vision completely recovered. We reported an atypical case of a sterile corneal ring infiltrate associated with soft contact lens wearing; smear, culture, and confocal microscopy confirmed a sterile inflammatory reaction.


Parent-of-origin in individuals with familial neurofibromatosis type 1 and optic pathway gliomas.
Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant cancer syndromes worldwide. Individuals with NF1 have a wide variety of clinical features including a strongly increased risk for pediatric brain tumors. The etiology of pediatric brain tumor development in NF1 is largely unknown. Recent studies have highlighted the contribution of parent-of-origin effects to tumorigenesis in sporadic cancers and cancer predisposition syndromes; however, there is limited data on this effect for cancers arising in NF1. To increase our understanding of brain tumor development in NF1, we conducted a multi-center retrospective chart review of 240 individuals with familial NF1 who were diagnosed with a pediatric brain tumor (optic pathway glioma; OPG) to determine whether a parent-of-origin effect exists overall or by the patient's sex. Overall, 50 % of individuals with familial NF1 and an OPG inherited the NF1 gene from their mother. Similarly, by sex, both males and females were as likely to inherit the NF1 gene from their mother as from their father, with 52 % and 48 % of females and males with OPGs inheriting the NF1 gene from their mother. In conclusion, in contrast to findings from other studies of sporadic cancers and cancer predisposition syndromes, our results indicate no parent-of-origin effect overall or by patient sex for OPGs in NF1.


Small EUS-suspected gastrointestinal stromal tumors of the stomach: An overview for the current state of management.
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors found in the gastrointestinal (GI) tract, with the stomach being the most common site. They represent a distinct group of GI tumors originating from the interstitial cells of Cajal and are characterized by gain-of-function mutations of KIT. KIT oncoprotein serves as both diagnostic and therapeutic targets. Prognosis is related to size, mitotic activity, and site of the tumor. Asymptomatic, small endoscopic ultrasonography (EUS)-suspected GISTs are increasingly encountered with the wide availability of endoscopic/endosonographic examination. The majority of small GISTs are biologically indolent, albeit possibly harboring c-KIT gene mutations. An ongoing controversy exists regarding the management and surveillance policy for small gastric GISTs. A number of reports on the management of GISTs have been published, not confidently addressing the issue of gastric GISTs of small size. This work provides an overview on the current state of management considerations, specifically focusing on small EUS-suspected gastric GISTs, which are increasingly encountered by clinicians.


Topical cidofovir for plantar warts.
Plantar warts are a common reason for dermatological consultations and their treatment can occasionally be a challenge. Plantar warts are benign lesions produced by the human papillomavirus (HPV) that often fail to respond to habitual treatment. Cidofovir is a potent antiviral drug that acts competitively, inhibiting viral DNA polymerase. Our aim was to assess the efficacy and safety of cidofovir cream for the treatment of viral plantar warts. We undertook a retrospective observational study of patients with plantar warts who received treatment with topical cidofovir between July 2008 and July 2011 at the Dermatology Service of the Hospital Costa del Sol, Marbella, Spain. Data about the rate of treatment response, the adverse effects, and recurrences, as well as the characteristics of the patient cohort, were recorded. We identified 35 patients who had received some previous treatment. The usual concentration was 3% (in 33 of 35 cases), applied twice a day (in 31 of 35 cases). A greater or lesser response was noted in 28 cases. There were two recurrences. Topical cidofovir seems to be a useful alternative for the therapeutic management of recalcitrant plantar common warts that fail to respond to usual treatment.


Evaluating the feasibility of performing window of opportunity trials in breast cancer.
The waiting period to surgery represents a valuable "window of opportunity" to evaluate novel therapeutic strategies. Interventional studies performed during this period require significant multidisciplinary collaboration to overcome logistical hurdles. We undertook a one-year prospective window of opportunity study to assess feasibility. Eligible newly diagnosed postmenopausal, estrogen receptor positive breast cancer patients awaiting primary surgery received anastrozole daily until surgery. Feasibility was assessed by (a) the proportion of patients who consented and (b) completed the study. Comparison of pre- and poststudy Ki67 labelling index and cleaved caspase 3 scores (CC3) was performed. 22/131 (16.8%) patients were confirmed eligible and 20/22 (91%) patients completed the study. 19/20 (95%) patients agreed to undergo optional additional tissue biopsies. The mean duration of anastrozole use was 24.7 (15-44) days. There were a statistically significant decline in mean Ki67 indices of 48.8% (p < 0.001) and a trend towards significance in the decline of CC3 (p = 0.17) when comparing pre- with posttreatment values. window of opportunity trials in breast cancer are a feasible way of assessing the biologic efficacy of different therapies in the presurgical setting. The majority of eligible women were willing to participate including undergoing additional tissue biopsies.


Optical frequency domain imaging with a rapidly swept laser in the 815-870 nm range.
Optical frequency domain imaging (OFDI) in the 800-nm biological imaging window is demonstrated by using a novel wavelength-swept laser source. The laser output is tuned continuously from 815 to 870 nm at a 43.2-kHz repetition rate with 7-mW average power. Axial resolution of 10-mum in biological tissue and peak sensitivity of 96 dB are achieved. In vivo imaging of Xenopus laevis is demonstrated with an acquisition speed of 84 frames per second (512 axial lines per frame). This new imaging technique may prove useful in comprehensive retinal screening for medical diagnosis and contrast-agent-based imaging for biological investigations.


Phenolic Compounds Content and Genetic Diversity at Population Level across the Natural Distribution Range of Bearberry (Arctostaphylos uva-ursi, Ericaceae) in the Iberian Peninsula.
Bearberry (Arctostaphylos uva-ursi) is a medicinal plant traditionally employed for the treatment of urinary tract infections due to high contents of arbutin (hydroquinone β-D-glucoside), which is now mainly used as a natural skin-whitening agent in cosmetics. Bearberry has also been proposed as a natural antioxidant additive due to the high contents of phenolic compounds in leaves. We studied the variation on phenolic compounds in 42 wild populations of bearberry, aiming to elucidate if intrinsic biological, climatic, and/or geographic factors affect phenolic contents across its natural distribution in the Iberian Peninsula. Bearberry leaves were collected during autumn over a three-year period (2014-2016) in populations across a latitude and altitude gradient. Methanolic extracts showed a wide range of variation in total phenols content, and different phenolic profiles regarding arbutin (levels of this major constituent varied from 87 to 232 mg/g dr wt), but also catechin and myricetin contents, which were affected by geographic and climatic factors. Moderate levels of variation on genome size-assessed by flow cytometry-and on two plastid DNA regions were also detected among populations. Genetic and cytogenetic differentiation of populations was weakly but significantly associated to phytochemical diversity. Elite bearberry genotypes with higher antioxidant capacity were subsequently identified.


O-GlcNAc-specific antibody CTD110.6 cross-reacts with N-GlcNAc2-modified proteins induced under glucose deprivation.
Modification of serine and threonine residues in proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is a feature of many cellular responses to the nutritional state and to stress. O-GlcNAc modification is reversibly regulated by O-linked β-N-acetylglucosamine transferase (OGT) and β-D-N-acetylglucosaminase (O-GlcNAcase). O-GlcNAc modification of proteins is dependent on the concentration of uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc), which is a substrate of OGT and is synthesized via the hexosamine biosynthetic pathway. Immunoblot analysis using the O-GlcNAc-specific antibody CTD110.6 has indicated that glucose deprivation increases protein O-GlcNAcylation in some cancer cells. The mechanism of this paradoxical phenomenon has remained unclear. Here we show that the increased glycosylation induced by glucose deprivation and detected by CTD110.6 antibodies is actually modification by N-GlcNAc(2), rather than by O-GlcNAc. We found that this induced glycosylation was not regulated by OGT and O-GlcNAcase, unlike typical O-GlcNAcylation, and it was inhibited by treatment with tunicamycin, an N-glycosylation inhibitor. Proteomics analysis showed that proteins modified by this induced glycosylation were N-GlcNAc(2)-modified glycoproteins. Furthermore, CTD110.6 antibodies reacted with N-GlcNAc(2)-modified glycoproteins produced by a yeast strain with a ts-mutant of ALG1 that could not add a mannose residue to dolichol-PP-GlcNAc(2). Our results demonstrated that N-GlcNAc(2)-modified glycoproteins were induced under glucose deprivation and that they cross-reacted with the O-GlcNAc-specific antibody CTD110.6. We therefore propose that the glycosylation status of proteins previously classified as O-GlcNAc-modified proteins according to their reactivity with CTD110.6 antibodies must be re-examined. We also suggest that the repression of mature N-linked glycoproteins due to increased levels of N-GlcNAc(2)-modified proteins is a newly recognized pathway for effective use of sugar under stress and deprivation conditions. Further research is needed to clarify the physiological and pathological roles of N-GlcNAc(2)-modified proteins.


Integrating single-cell transcriptomic data across different conditions, technologies, and species.
Computational single-cell RNA-seq (scRNA-seq) methods have been successfully applied to experiments representing a single condition, technology, or species to discover and define cellular phenotypes. However, identifying subpopulations of cells that are present across multiple data sets remains challenging. Here, we introduce an analytical strategy for integrating scRNA-seq data sets based on common sources of variation, enabling the identification of shared populations across data sets and downstream comparative analysis. We apply this approach, implemented in our R toolkit Seurat (http://satijalab.org/seurat/), to align scRNA-seq data sets of peripheral blood mononuclear cells under resting and stimulated conditions, hematopoietic progenitors sequenced using two profiling technologies, and pancreatic cell 'atlases' generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across data sets, while boosting statistical power through integrated analysis. Our approach facilitates general comparisons of scRNA-seq data sets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution.


Can UV radiation affect benthic deposit-feeders through biochemical alteration of food resources? An experimental study with juveniles of the benthic polychaete Eupolymnia nebulosa.
The growth, tentacle development and feeding activity of the benthic polychaete Eupolymnia nebulosa were examined to determine whether UV might affect marine deposit-feeders indirectly through the modification of the nutritional quality of their resources. Since marine invertebrates have higher nutritional requirements during the period following settlement, we tested the effect of UV-altered phytodetritus on freshly settled juveniles of E. nebulosa. Phytodetritus was prepared from cultures of the diatom Skeletonema costatum either grown under or sheltered from UVB radiation. Sterol content of phytodetritus was unmodified by UV radiation. Conversely, phytodetritus was noticeably depleted in polyunsaturated fatty acids. Growth and tentacle development of juveniles fed on altered phytodetritus were reduced by 35% and 15% respectively, suggesting potential deficiencies in essential nutrients. In response to the lower quality of the phytodetritus, juveniles explored a wider area as they search for food, a strategy that could compensate for low food quality.


Developing a professional-practice-model-based nursing organizational informatics competency model.
The development of nursing informatics started late in China. There is an urgent need to develop a clinical practice model that can guide nursing managers in constructing an organizational nursing informatics competency. The objective of this study was to develop a nursing organizational informatics competency model based on the Professional Practice Model (PPM) and to provide a reference for training in clinical nursing informatics in hospitals. A multidisciplinary team in the hospital was first formed as the working group, consisting of nurses trained with the TIGER (Technology Informatics Guiding Education Reform) Taiwan model and had practical experience in system development. We used an exploration map to help build the prototype of the hospital nursing informatics competency model. Then, a final model was constructed by experienced out-of-hospital experts using the Delphi method. The final model was determined according to the validity analysis. Ten hospital stakeholders were invited to form the multidisciplinary working team to develop the prototype organizational PPM model. Two rounds of Delphi were conducted to twelve experienced nurses' informatics experts outside the hospital by e-mail. The results showed that the questionnaire return rate was 100 %, the expert authority coefficient was 0.84, the general validity of the two rounds of content was 92.46 % and 100 %, respectively, and the coefficient of variation of all items was < 0.3. The final model included five categories, including management strategy and leadership, organizational structure and operation, improvement of the environment for nursing information practice, cultivation of core competence in nursing information, and project management of the nursing information system, with 61 elements in total. We propose this model to help hospital nursing managers to establish a plan of action to build up organizational clinical informatics competency.


Cascade and Fusion: A Deep Learning Approach for Camouflaged Object Sensing.
The demand for the sensor-based detection of camouflage objects widely exists in biological research, remote sensing, and military applications. However, the performance of traditional object detection algorithms is limited, as they are incapable of extracting informative parts from low signal-to-noise ratio features. To address this problem, we propose Camouflaged Object Detection with Cascade and Feedback Fusion (CODCEF), a deep learning framework based on an RGB optical sensor that leverages a cascaded structure with Feedback Partial Decoders (FPD) instead of a traditional encoder-decoder structure. Through a selective fusion strategy and feedback loop, FPD reduces the loss of information and the interference of noises in the process of feature interweaving. Furthermore, we introduce Pixel Perception Fusion (PPF) loss, which aims to pay more attention to local pixels that might become the edges of an object. Experimental results on an edge device show that CODCEF achieved competitive results compared with 10 state-of-the-art methods.


Label-free voltammetric detection of single-nucleotide mismatches recognized by the protein MutS.
MutS, a protein involved in DNA mismatch repair, recognizes mispaired and unpaired bases in duplex DNA. We have previously used MutS in an electrochemical double-surface technique (DST) for in-vitro detection of point mutations in DNA. The DST involved binding of unlabeled MutS to DNA heteroduplexes at the surface of magnetic beads followed by a highly sensitive electrochemical determination of the protein by measurement of a catalytic protein signal (peak H) at mercury electrodes. Detection of MutS using a peak resulting from oxidation of tyrosine and tryptophan residues of the protein at a carbon-paste electrode (CPE) was also possible but was approximately three orders of magnitude less sensitive. In this work we present an optimized technique for ex-situ voltammetric determination of MutS at a CPE. Choice of optimum experimental conditions (pH of supporting electrolyte, square-wave voltammetry settings, etc.) resulted in substantial improvement of the sensitivity of the assay, enabling detection of approximately 140 pg (1.6 fmol protein monomer) MutS in a 5-microL sample. The sensitivity was increased further by acid hydrolysis of the protein before measurement. The hydrolyzed protein was detectable down to 5 pg (approx. 56 amol) MutS in 5 microL solution. By using the DST combined with determination of the bound unlabeled MutS at the CPE we demonstrated selective interactions of the protein with single-base mismatches and discrimination among different base mispairs in 30-mer or 95-mer DNA duplexes. In agreement with previous studies, binding of the protein to the 30-mer substrates followed the trend G:T>>C:A>A:A>C:T>homoduplex. The electrochemical data were confirmed by use of an independent technique-a quartz-crystal microbalance for real-time monitoring of MutS interactions with DNA duplexes containing different base mispairs. By using the electrochemical DST a G:T mismatch was detectable in up to 1000-fold excess of homoduplex DNA.


Can race really be erased? A pre-registered replication study.
WHEN ENCOUNTERING AN UNKNOWN INDIVIDUAL, SOCIAL CATEGORIZATION OF THE INDIVIDUAL HAS BEEN SHOWN TO AUTOMATICALLY PROCEED ON THE BASIS OF THREE FUNDAMENTAL DIMENSIONS: People seem to mandatorily encode race, sex and age. In contradiction to this general finding, Kurzban et al. (2001) showed that race encoding is not automatic and inevitable, but rather a byproduct of categorization in terms of coalitions. In particular, they argue and empirically support that when other coalitional information is present, the encoding of race is spectacularly reduced. In the present contribution, we present a replication of the race-erased effect reported by Kurzban et al. First, we give a detailed overview of the hypotheses, the experimental methodology, the derivation of the sample size required to achieve a power of 95%, and the criteria that need to be met for a successful replication. Then we present the findings of an empirical test that met the requirements of our power analyses. Our results indicate that the encoding of race is indeed reduced when another coalitional cue is available, yet this reduction is less marked than in the original study. This experiment was preregistered before data collection at Open Science Framework, osf.io/vnhrm/.


Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands.
One of the major reasons for failure of radiotherapeutic cancer treatment is the limitation in dose that can be applied to the tumor because of coirradiation of the normal healthy tissue. Late radiation-induced damage reduces the quality of life of the patient and may even be life threatening. Replacement of the radiation-sterilized stem cells with unirradiated autologous stem cells may restore the tissue function. Here, we assessed the potential of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow-derived cells (BMC) to regenerate and functionally restore irradiated salivary glands used as a model for normal tissue damage. Male-eGFP+ bone marrow chimeric female C57BL/6 mice were treated with G-CSF, 10 to 60 days after local salivary gland irradiation. Four months after irradiation, salivary gland morphology and flow rate were assessed. G-CSF treatment induced homing of large number of labeled BMCs to the submandibular glands after irradiation. These animals showed significant increased gland weight, number of acinar cells, and salivary flow rates. Donor cells expressed surface markers specific for hematopoietic or endothelial/mesenchymal cells. However, salivary gland acinar cells neither express the G-CSF receptor nor contained the GFP/Y chromosome donor cell label. The results show that BMCs home to damaged salivary glands after mobilization and induce repair processes, which improve function and morphology. This process does not involve transdifferentiation of BMCs to salivary gland cells. Mobilization of BMCs could become a promising modality to ameliorate radiation-induced complications after radiotherapy.


Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly.
Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ~80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices.


Contingent gambling-drinking patterns and problem drinking severity moderate implicit gambling-alcohol associations in problem gamblers.
Although problem gambling and problem drinking often co-occur, the processes underlying this association are not well understood. This study investigated the effects of contingent gambling-drinking patterns and problem drinking severity on implicit gambling-alcohol associations. Participants were 144 (34 female) problem gamblers. The South Oaks Gambling Screen (SOGS) measured severity of problem gambling. The Brief Michigan Alcohol Screening Test (BMAST) measured severity of problem drinking. The Implicit Association Test (Greenwald, McGhee, & Schwartz, 1998, Journal of Personality and Social Psychology, 74, 1464-1480) measured gambling-alcohol associations. Participants who reported drinking when they won displayed faster response time (i.e., priming) on trials where alcohol words were paired with gambling win (e.g., jackpot) vs. gambling loss (e.g., forfeit) words. The tendency to drink in response to losses did not influence the priming effect of win cues or moderate the effects of Win-Drinking Pattern on priming. Severity of problem drinking on the BMAST also correlated positively the priming effects of win cues. These findings indicate that a tendency to drink in response to gambling wins and more severe alcohol problems each coincide with stronger associations between gambling win and alcohol concepts in memory. Such associations can promote drinking and its attendant effects (e.g., poor decision-making) in problem gamblers, and thus, may contribute to co-morbid gambling and alcohol use disorders.


Sufficient Volume Ablation with Photoselective Vaporization of the Prostate Delivers 5-Year Durability and Improves Symptom Relief for Larger Prostates.
To assess the long-term durability of photoselective vaporization of the prostate (PVP) for symptomatic benign prostatic enlargement (BPE) or benign prostatic obstruction (BPO) and treatment efficacy for large BPE. Four hundred fifty-seven patients with symptomatic BPE underwent PVP between January 2006 and April 2009. Efficacy was evaluated with the International Prostate Symptoms Score (IPSS), Quality of Life (QOL) score, urinary peak flow (Qmax), postvoid residual volume (PVR), and prostate volume. Parameters were checked preoperatively, and at 1, 3, and 5 years postoperatively. One hundred fifty-three patients completed 5-year follow-up. To assess treatment effects, patients were divided into two groups according to the preoperative prostate volume: group A (<60 mL, n=104) and group B (>60 mL, n=49). Mean IPSS, QOL score, Qmax, and PVR improved significantly and were maintained for 5 years with no significant differences; at year 1, prostate volume had decreased significantly from 54.0 mL to 30.6 mL (43% of volume ablation) and remained at that level until year 5. Investigations according to prostate size demonstrate that IPSS and QOL scores in group B remained at significantly lower levels, and Qmax in group B improved more than in group A. 1.1% of patients needed transurethral resection of the prostate due to BPO recurrence. PVP is effective and provides durable results for 5 years, with sustained symptom relief and improved urinary flow rate, as well as a 43% volume reduction of prostate volume. Our data indicate PVP is more efficacious for larger prostates under sufficient volume ablation.


Pool walking may improve renal function by suppressing the renin-angiotensin-aldosterone system in healthy pregnant women.
This study aimed to examine the effect of pool walking on renal function in pregnant women. Fifteen pregnant women (mean gestational age, 37.8 weeks) walked in a pool (depth 1.3 m) for 1 h. A few days later, they walked on a street for 1 h. Within each activity, the starting and ending levels of plasma renin activity were measured. The total urine volume, creatinine clearance, and change in plasma renin activity levels between each activity were compared by Wilcoxon rank-sum test. The renin-angiotensin-aldosterone level was suppressed during pool walking: the mean starting and ending values of plasma renin activity and serum aldosterone were 6.8 vs. 5.5 ng/mL/h (p = 0.002) and 654 vs. 473 pg/mL (p = 0.01), respectively. The decreases in plasma renin activity and serum aldosterone levels were more evident in pool walking than in land walking (plasma renin activity, -1.27 vs. 0.81 ng/mL/h, p = 0.002; serum aldosterone, -180.9 vs. 3.1 ng/mL/h, p = 0.03), resulting in higher total urine volume (299 vs. 80 mL, p < 0.001) and creatinine clearance (161.4 vs. 123.4 mL/min, p = 0.03) in pool walking. Pool walking may improve renal function in pregnant women partly through the suppressed renin-angiotensin-aldosterone system.


The laminar profile of sleep spindles in humans.
Sleep spindles are functionally important NREM sleep EEG oscillations which are generated in thalamocortical, corticothalamic and possibly cortico-cortical circuits. Previous hypotheses suggested that slow and fast spindles or spindles with various spatial extent may be generated in different circuits with various cortical laminar innervation patterns. We used NREM sleep EEG data recorded from four human epileptic patients undergoing presurgical electrophysiological monitoring with subdural electrocorticographic grids (ECoG) and implanted laminar microelectrodes penetrating the cortex (IME). The position of IMEs within cortical layers was confirmed using postsurgical histological reconstructions. Many spindles detected on the IME occurred only in one layer and were absent from the ECoG, but with increasing amplitude simultaneous detection in other layers and on the ECoG became more likely. ECoG spindles were in contrast usually accompanied by IME spindles. Neither IME nor ECoG spindle cortical profiles were strongly associated with sleep spindle frequency or globality. Multiple-unit and single-unit activity during spindles, however, was heterogeneous across spindle types, but also across layers and patients. Our results indicate that extremely local spindles may occur in any cortical layer, but co-occurrence at other locations becomes likelier with increasing amplitude and the relatively large spindles detected on ECoG channels have a stereotypical laminar profile. We found no compelling evidence that different spindle types are associated with different laminar profiles, suggesting that they are generated in cortical and thalamic circuits with similar cortical innervation patterns. Local neuronal activity is a stronger candidate mechanism for driving functional differences between spindles subtypes.


Women's health and hygiene experiences during deployment to the Iraq and Afghanistan wars, 2003 through 2010.
The purpose of this study was to describe women's health and hygiene experiences during their deployment to Iraq and Afghanistan during the war years, 2003 through 2010. A phenomenological method described the essential structures embedded in the women's health and hygiene experiences. Colaizzi's method of data analysis was used to guide the discovery of themes. Interview data were gathered from 24 interviews with military nurses who served in the war zones. Female military nurses were specifically selected for this study because of their insight, awareness, and knowledge base. Seven themes emerged from the data and captured the essence of the women's experiences: 1) bathroom trips and facilities: a walk on the wild side; 2) shower challenges: lack of privacy, water problems, and location issues; 3) menstruation: to suppress or not to suppress; 4) staying clean: a monumental task; 5) various infections: annoying distractions; 6) unintended pregnancies: wartime surprises; and 7) safety issues: enemy attacks and sexual assaults. In the current military structure, more women are being deployed to combat zones and will endure the challenges and hardships described in this study. The health and hygiene experiences of deployed women are an important part of their daily lives in combat zones. Educational programs and clinical services need to be tailored to this cadre of women, with focused attention on preparation and anticipatory guidance prior to deployment. Access to health promotion and appropriate clinical services during deployment is critical. Finally, as these women return home as veterans, it is important for all providers to understand the contextual framework of their service and its impact on their lives.


Expression of an exogenous isopentenyl diphosphate isomerase gene enhances isoprenoid biosynthesis in Escherichia coli.
Escherichia coli expressing the Erwinia carotenoid biosynthesis genes, crtE, crtB, crtI and crtY, form yellow-coloured colonies due to the presence of beta-carotene. This host was used as a visible marker for evaluating regulatory systems operating in isoprenoid biosynthesis of E. coli. cDNAs enhancing carotenoid levels were isolated from the yeast Phaffia rhodozyma and the green alga Haematococcus pluvialis. Nucleotide sequence analysis indicated that they coded for proteins similar to isopentenyl diphosphate (IPP) isomerase of the yeast Saccharomyces cerevisiae. Determination of enzymic activity confirmed the identity of the gene products as IPP isomerases. The corresponding gene was isolated from the genomic library of S. cerevisiae based on its nucleotide sequence, and was confirmed to have the same effect as the above two IPP isomerase genes when introduced into the E. coli transformant accumulating beta-carotene. In the three E. coli strains carrying the individual exogenous IPP isomerase genes, the increases in carotenoid levels are comparable to the increases in IPP isomerase enzyme activity with reference to control strains possessing the endogenous gene alone. These results imply that IPP isomerase forms an influential step in isoprenoid biosynthesis of the prokaryote E. coli, with potential for the efficient production of industrially useful isoprenoids by metabolic engineering.


'Fit to fly': overcoming barriers to preoperative haemoglobin optimization in surgical patients.
In major surgery, the implementation of multidisciplinary, multimodal and individualized strategies, collectively termed Patient Blood Management, aims to identify modifiable risks and optimise patients' own physiology with the ultimate goal of improving outcomes. Among the various strategies utilized in Patient Blood Management, timely detection and management of preoperative anaemia is most important, as it is in itself a risk factor for worse clinical outcome, but also one of the strongest predisposing factors for perioperative allogeneic blood transfusion, which in turn increases postoperative morbidity, mortality and costs. However, preoperative anaemia is still frequently ignored, with indiscriminate allogeneic blood transfusion used as a 'quick fix'. Consistent with reported evidence from other medical specialties, this imprudent practice continues to be endorsed by non-evidence based misconceptions, which constitute serious barriers for a wider implementation of preoperative haemoglobin optimisation. We have reviewed a number of these misconceptions, which we unanimously consider should be promptly abandoned by health care providers and replaced by evidence-based strategies such as detection, diagnosis and proper treatment of preoperative anaemia. We believe that this approach to preoperative anaemia management may be a viable, cost-effective strategy that is beneficial both for patients, with improved clinical outcomes, and for health systems, with more efficient use of finite health care resources.