High-efficiency hybrid computer-generated holograms.
A hybrid hologram is constructed which combines the flexibility of a computer-generated hologram (CGH) with the high-diffraction efficiency of volume phase holograms. The new hologram is constructed by using a spatially filtered wave front from a conventional 246- x 256-cell CGH as the object wave for the recording of a volume hologram. Theoretical and experimental results show that simultaneous high-diffraction efficiency and reconstruction fidelity are possible.


Highly potent, synthetically accessible prostratin analogs induce latent HIV expression in vitro and ex vivo.
Highly active antiretroviral therapy (HAART) decreases plasma viremia below the limits of detection in the majority of HIV-infected individuals, thus serving to slow disease progression. However, HAART targets only actively replicating virus and is unable to eliminate latently infected, resting CD4(+) T cells. Such infected cells are potentially capable of reinitiating virus replication upon cessation of HAART, thus leading to viral rebound. Agents that would eliminate these reservoirs, when used in combination with HAART, could thus provide a strategy for the eradication of HIV. Prostratin is a preclinical candidate that induces HIV expression from latently infected CD4(+) T cells, potentially leading to their elimination through a virus-induced cytopathic effect or host anti-HIV immunity. Here, we report the synthesis of a series of designed prostratin analogs and report in vitro and ex vivo studies of their activity relevant to induction of HIV expression. Members of this series are up to 100-fold more potent than the preclinical lead (prostratin) in binding to cell-free PKC, and in inducing HIV expression in a latently infected cell line and prostratin-like modulation of cell surface receptor expression in primary cells from HIV-negative donors. Significantly, selected members were also tested for HIV induction in resting CD4(+) T cells isolated from infected individuals receiving HAART and were found to exhibit potent induction activity. These more potent agents and by extension related tunable analogs now accessible through the studies described herein should facilitate research and preclinical advancement of this strategy for HIV/AIDS eradication.


Transcriptional profiling in Candida albicans reveals new adaptive responses to extracellular pH and functions for Rim101p.
The human pathogen Candida albicans grows and colonizes sites that can vary markedly in pH. The pH response in C. albicans is governed in part by the Rim101p pathway. In Saccharomyces cerevisiae, Rim101p promotes alkaline responses by repressing expression of NRG1, itself a transcriptional repressor. Our studies reveal that in C. albicans, Rim101p-mediated alkaline adaptation is not through repression of CaNRG1. Furthermore, our studies suggest that Rim101p and Nrg1p act in parallel pathways to regulate hyphal morphogenesis, an important contributor to virulence. To determine the wild-type C. albicans transcriptional response to acidic and alkaline pH, we utilized microarrays and identified 514 pH-responsive genes. Of these, several genes involved in iron acquisition were upregulated at pH 8, suggesting that alkaline pH induces iron starvation. Microarray analysis of rim101-/- cells indicated that Rim101p does not govern transcriptional responses at acidic pH, but does regulate a subset of transcriptional responses at alkaline pH, including the iron acquisition genes. We found that rim101-/- cells are sensitive to iron starvation, which suggests that one important aspect of the Rim101p-dependent alkaline pH response is to adapt to iron starvation conditions.


Detection of codeine and fentanyl in saliva, blood plasma and whole blood in 5-minutes using a SERS flow-separation strip.
A simple-to-use device to measure drugs in saliva, blood plasma, and whole blood for point-of-care analysis and treatment of overdose patients has been investigated. A rudimentary flow strip has been developed to separate opioids from these biofluids for analysis by surface-enhanced Raman spectroscopy (SERS). The strips are based on lateral flow assays, in which the antibodies have been substituted by SERS-active pads for detection. Samples of codeine and fentanyl, artificially added to these biofluids, were measured using the strips by a field-usable Raman spectrometer. We report measurement of these drugs in these biofluids from 0.5 to 5 μg mL-1 in 5 minutes. Calculated limits of detection for the spectra suggest that these drugs could be measured at 5 to 20 ng mL-1 with improvements in the strips' separation capability.


Health insurance coverage of immigrants living in the United States: differences by citizenship status and country of origin.
This study examined health insurance coverage among immigrants who are not US citizens and among individuals from the 16 countries with the largest number of immigrants living in the United States. We analyzed data from the 1998 Current Population Survey, using logistic regression to standardize rates of employer-sponsored coverage by country of origin. In 1997, 16.7 million immigrants were not US citizens. Among non-citizens, 43% of children and 12% of elders lacked health insurance, compared with 14% of non-immigrant children and 1% of non-immigrant elders. Approximately 50% of non-citizen full-time workers had employer-sponsored coverage, compared with 81% of non-immigrant full-time workers. Immigrants from Guatemala, Mexico, El Salvador, Haiti, Korea, and Vietnam were the most likely to be uninsured. Among immigrants who worked full-time, sociodemographic and employment characteristics accounted for most of the variation in employer health insurance. For Central American immigrants, legal status may play a role in high un-insurance rates. Immigrants who are not US citizens are much less likely to receive employer-sponsored health insurance or government coverage; 44% are uninsured. Ongoing debates on health insurance reform and efforts to improve coverage will need to focus attention on this group.


Liver Matrix in Benign and Malignant Biliary Tract Disease.
The extracellular matrix is a highly reactive scaffold formed by a wide array of multifunctional molecules, encompassing collagens and noncollagenous glycoproteins, proteoglycans, glycosaminoglycans, and polysaccharides. Besides outlining the tissue borders, the extracellular matrix profoundly regulates the behavior of resident cells by transducing mechanical signals, and by integrating multiple cues derived from the microenvironment. Evidence is mounting that changes in the biostructure of the extracellular matrix are instrumental for biliary repair. Following biliary damage and eventually, malignant transformation, the extracellular matrix undergoes several quantitative and qualitative modifications, which direct interactions among hepatic progenitor cells, reactive ductular cells, activated myofibroblasts and macrophages, to generate the ductular reaction. Herein, we will give an overview of the main molecular factors contributing to extracellular matrix remodeling in cholangiopathies. Then, we will discuss the structural alterations in terms of biochemical composition and physical stiffness featuring the "desmoplastic matrix" of cholangiocarcinoma along with their pro-oncogenic effects.


In vivo phosphorylation and protein analysis of hepatitis B virus core antigen.
The C open reading frame of the hepatitis B virus contains two in-frame ATG codons that are separated by the precore region and encodes two major polypeptides that are antigenically distinct and that are probably synthesized from individual mRNAs. The precore region directs the secretion of the e antigen, whereas the core antigen can be expressed in the absence of these sequences. In this report a transient expression system was used to study the hepatitis B virus core antigen. By using a chimeric complex of adenovirus major late promoter-simian virus 40 enhancer sequences, we were able to achieve high levels of core antigen expression in transfected cells, permitting characterization of this protein and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The core polypeptide is a 20.9-kilodalton protein, and we show in this study that it is phosphorylated in vivo. Cell fractionation studies, the results of which are supported by indirect immunofluorescence, localized the phosphocore in the cytosol and the nucleus and indicated that it is associated with the membrane of transfected cells. Results of Triton X-114 solubilization studies indicated that the phosphocore is peripherally associated with cytoplasmic membranes. Expression of the membrane-associated phosphocore occurred in the absence of the precore sequences. The phosphocore also assembled into particles in the absence of other viral gene products or intact DNA.


Progenitor cell isolation from muscle-derived cells based on adhesion properties.
Adult skeletal muscle possesses remarkable regenerative capacity that has conventionally been attributed to the satellite cells. These precursor cells were thought to contain distinct populations with varying myogenic potential. Recently, the identification of multipotent stem cells capable of new myofiber formation has expanded the general view on the muscle regenerative process. Here we examined the characteristics of turkey skeletal muscle-derived cell (MDC) populations that were separated according to their adhesion abilities. We sought to determine whether these abilities could be a potential tool for separating cells with different myogenic commitment. Using the preplate technique, we showed that MDCs display a wide range of adhesion ability, allowing us to isolate a marginal fraction with initial adhesion defect. Methodological investigations revealed that this defect represents an intrinsic and well-established biological feature for these cells. In vitro behavioral and morphological analyses showed that late adherent cells (LACs) share several primitive cell characteristics. Phenotypic assessment indicated that LACs contain early stage myogenic cells and immature progenitors of satellite cells, whereas early adherent cells consist mainly of fully committed precursors. Overall, our findings demonstrate for the first time in an avian model that differential MDC adhesion properties could be used to efficiently purify cells with varying myogenic commitment, including immature progenitor cells. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.


Metastatic esophageal carcinoma to the eye masquerading as inflammatory vitreo-retinitis: A case report and literature review.
We report an unusual case of metastatic esophageal carcinoma to the vitreous associated with focal retinitis in a 44-year-old male. A 44-year-old male patient, known case of locally advanced esophageal carcinoma, presented with a 3-day history of left eye floaters. The initial diagnosis was inflammatory vitreo-retinitis that responded to systemic steroids. Four months later, the patient presented with relapsed intraocular inflammation, vitreous biopsy using a 25G needle was performed, and cytology confirmed the presence of metastatic carcinoma consistent with his primary esophageal cancer. The patient received external beam radiotherapy to his ocular and brain metastasis, and his eye examination was stable. Five months later, the patient passed away due to progressive brain metastasis.


elPrep: High-Performance Preparation of Sequence Alignment/Map Files for Variant Calling.
elPrep is a high-performance tool for preparing sequence alignment/map files for variant calling in sequencing pipelines. It can be used as a replacement for SAMtools and Picard for preparation steps such as filtering, sorting, marking duplicates, reordering contigs, and so on, while producing identical results. What sets elPrep apart is its software architecture that allows executing preparation pipelines by making only a single pass through the data, no matter how many preparation steps are used in the pipeline. elPrep is designed as a multithreaded application that runs entirely in memory, avoids repeated file I/O, and merges the computation of several preparation steps to significantly speed up the execution time. For example, for a preparation pipeline of five steps on a whole-exome BAM file (NA12878), we reduce the execution time from about 1:40 hours, when using a combination of SAMtools and Picard, to about 15 minutes when using elPrep, while utilising the same server resources, here 48 threads and 23GB of RAM. For the same pipeline on whole-genome data (NA12878), elPrep reduces the runtime from 24 hours to less than 5 hours. As a typical clinical study may contain sequencing data for hundreds of patients, elPrep can remove several hundreds of hours of computing time, and thus substantially reduce analysis time and cost.


[End of the use of masks in public spaces during the COVID-19 pandemic: impact on the mental health of pregnant women].
COVID-19 has affected the entire population, generating a greater impact on certain vulnerable groups, such as pregnant women. The aim of this study was to evaluate the levels of fear and anxiety regarding the COVID-19 disease in pregnant women, using the AMICO_Pregnant scale, in the final phase of the health crisis caused by the disease, marked by the relaxation of isolation measures in public spaces. A descriptive cross-sectional study using the self-reported questionnaire AMICO_Pregnant was developed between March 24 and April 18, 2022. This was followed by a univariate and bivariate statistical analysis of the data collected. A total of 479 surveys of pregnant women of different gestational ages were obtained. The bivariate analysis showed statistical significance in the AMICO_Pregnant scale score about several variables over the previous year: contact with the disease (p=0.025); number of previous pregnancies (p=0.019); changes in the birth plan (p=0.001); and vaccination status (p=0.01). The COVID-19 pandemic has impacted pregnant women's mental health, producing a negative effect on emotions. The research carried out shows a statistically significant relationship between the levels of fear and anxiety in pregnant women and factors such as the number of previous pregnancies, contact with the previous disease, vaccination level or expectations regarding the delivery or birth plan.


Characterization of the complete fiber network topology of planar fibrous tissues and scaffolds.
Understanding how engineered tissue scaffold architecture affects cell morphology, metabolism, phenotypic expression, as well as predicting material mechanical behavior has recently received increased attention. In the present study, an image-based analysis approach that provides an automated tool to characterize engineered tissue fiber network topology is presented. Micro-architectural features that fully defined fiber network topology were detected and quantified, which include fiber orientation, connectivity, intersection spatial density, and diameter. Algorithm performance was tested using scanning electron microscopy (SEM) images of electrospun poly(ester urethane)urea (ES-PEUU) scaffolds. SEM images of rabbit mesenchymal stem cell (MSC) seeded collagen gel scaffolds and decellularized rat carotid arteries were also analyzed to further evaluate the ability of the algorithm to capture fiber network morphology regardless of scaffold type and the evaluated size scale. The image analysis procedure was validated qualitatively and quantitatively, comparing fiber network topology manually detected by human operators (n = 5) with that automatically detected by the algorithm. Correlation values between manual detected and algorithm detected results for the fiber angle distribution and for the fiber connectivity distribution were 0.86 and 0.93 respectively. Algorithm detected fiber intersections and fiber diameter values were comparable (within the mean +/- standard deviation) with those detected by human operators. This automated approach identifies and quantifies fiber network morphology as demonstrated for three relevant scaffold types and provides a means to: (1) guarantee objectivity, (2) significantly reduce analysis time, and (3) potentiate broader analysis of scaffold architecture effects on cell behavior and tissue development both in vitro and in vivo.


Photoinhibition in vivo and in vitro involves weakly coupled chlorophyll-protein complexes.
In the present study the analysis of the relation between the excited state population in the photosystem II (PSII) antenna and photoinactivation has been extended from an in vitro system, isolated thylakoids, to an in vivo system, Chlamydomonas reinhardtii cells. The results indicate that the excited state quenching by an added singlet quencher induces maximal protection against photoinhibition of about 30% of that expected on the basis of the observed light intensity-treatment time reciprocity rule. Similar results, obtained previously with thylakoids, have been interpreted in terms of damaged or incorrectly assembled complexes that play an important role in photoinhibition in the thylakoid membranes (Santabarbara, S., K. Neverov, F. M. Garlaschi, G. Zucchelli and R. C. Jennings [2001] Involvement of uncoupled antenna chlorophylls in photoinhibition in thylakoids. FEBS Lett. 491, 109-113.). In an attempt to better define this aspect, the photoinhibition action spectra were determined for mutant barley thylakoids, lacking the chlorophyll (Chl) a-b complexes of the outer antenna, and for its wild type. The results indicate that in both systems the action spectra are significantly blueshifted (2-4 nm) and are broader than the PSII absorption in the membranes. These data are interpreted in terms of a heterogeneous population of outer and inner antenna pigment-protein complexes that contain significant levels of uncoupled Chl.


Expectations of life and health among spinal cord injured adults.
While our understanding of aging and mortality in spinal cord injury is evolving, precise estimates are still not available for expectations of life and health following a spinal cord injury. In order to derive these estimates, information about mortality and health must be combined into a single estimate. Health expectancy estimates have been widely used in the literature of the last decade to try to understand the relationship between population health and survival, both in the general population and in special populations. This study brought the benefit of this methodology to the question of long-term survival following spinal cord injury. Specifically, the study aimed to calculate life and health expectancy in a population of spinal cord injured individuals; and to estimate the effect of factors associated with survival and health. The study involved a retrospective cohort, all of whom sustained a spinal cord injury between the ages of 25 and 34 years, and between 1945 and 1990. The study predicted a median survival time of 38 years post-injury, with 43% surviving at least 40 years. These findings suggest an increase in life expectancy of about 5 years over previous research on the same cohort. Factors affecting survival were age at injury, level and completeness of lesion. Expectations of health found in the present study are similar to those found in studies of the general population. This study showed seven remaining years of poor health expected at injury, and five remaining years expected at 40 years post injury, presumably occurring at the end of life.


[Egg ultrastructure in two Chilean moths: Ormiscodes socialis and Polythysana cinerascens (Lepidoptera: Saturniidae)].
The structure and ultra-structure of the eggs from Ormiscodes socialis (Feisthamel) and Polythysana cinerascens (Philippi) are described, considering shape, size, coloring when recently laid, oviposition type and aeropiles (quantity, distribution and proportion) in the micropilar area, among others. The ultra-structure is shown for primary cells, secondary cells, aeropiles and micropiles. A comparative table of the eggs of these species is presented and includes the previously described eggs of Adetomeris microphthalma (Philippi). Myoschilos oblonga Ruiz y Pavón (Santalaceae) is recorded as a new host for P. cinerascens.


Type II Secretion Promotes Bacterial Growth within the Legionella-Containing Vacuole in Infected Amoebae.
It was previously determined that the type II secretion system (T2SS) promotes the ability of Legionella pneumophila to grow in coculture with amoebae. Here, we discerned the stage of intracellular infection that is potentiated by comparing the wild-type and T2SS mutant legionellae for their capacity to parasitize Acanthamoeba castellanii Whereas the mutant behaved normally for entry into the host cells and subsequent evasion of degradative lysosomes, it was impaired in the ability to replicate, with that defect being first evident at approximately 9 h postentry. The replication defect was initially documented in three ways: by determining the numbers of CFU recovered from the lysates of the infected monolayers, by monitoring the levels of fluorescence associated with amoebal monolayers infected with green fluorescent protein (GFP)-expressing bacteria, and by utilizing flow cytometry to quantitate the amounts of GFP-expressing bacteria in individual amoebae. By employing confocal microscopy and newer imaging techniques, we further determined the progression in volume and shape of the bacterial vacuoles and found that the T2SS mutant grows at a decreased rate and does not attain maximally sized phagosomes. Overall, the entire infection cycle (i.e., entry to egress) was considerably slower for the T2SS mutant than it was for the wild-type strain, and the mutant's defect was maintained over multiple rounds of infection. Thus, the T2SS is absolutely required for L. pneumophila to grow to larger numbers in its intravacuolar niche within amoebae. Combining these results with those of our recent analysis of macrophage infection, T2SS is clearly a major component of L. pneumophila intracellular infection.


Extreme multistability in symmetrically coupled clocks.
Extreme multistability (EM) is characterized by the emergence of infinitely many coexisting attractors or continuous families of stable states in dynamical systems. EM implies complex and hardly predictable asymptotic dynamical behavior. We analyze a model for pendulum clocks coupled by springs and suspended on an oscillating base and show how EM can be induced in this system by specifically designed coupling. First, we uncover that symmetric coupling can increase the dynamical complexity. In particular, the coexistence of multiple isolated attractors and continuous families of stable periodic states is generated in a symmetric cross-coupling scheme of four pendulums. These coexisting infinitely many states are characterized by different levels of phase synchronization between the pendulums, including anti-phase and in-phase states. Some of the states are characterized by splitting of the pendulums into groups with silent sub-threshold and oscillating behavior, respectively. The analysis of the basins of attraction further reveals the complex dependence of EM on initial conditions.


Unusual osseous presentation of blastomycosis in an immigrant child: a challenge for European pediatricians.
Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitidis is a systemic pyogranulomatous infection, endemic in United States and Canada, with few reported cases in Africa and Asia. It is uncommon among children and adolescents, ranging from 3% to 10%. Clinical features vary from asymptomatic spontaneously healing pneumonia, through acute or chronic pneumonia, to a malignant appearing lung mass. Blastomycosis can originate a "metastatic disease" in the skin, bones, genitourinary tract and central nervous system. Bone is the third most common site of blastomycotic lesions, after lung and skin. Bones may be involved in 14-60% of cases of blastomycosis. Direct visualization of single broadbased budding yeast with specific stains in sputum or tissue samples at microscopy is the primary method for diagnosis, while culture is timeconsuming and other methods are unreliable. We report a case of severe osteoarticular Blastomycosis occurring in a 3-years-old presented to our Emergency Department with pain and swelling of the left knee, successfully treated with surgical curettage and antifungal therapy. To our knowledge this is the first case reported in Europe. Blastomycosis represents a challenge for European physicians, and it should be included in the differential diagnosis of unexplained infections in patients coming from endemic areas.


Predictors of rational management of diarrhea in an endemic setting: observation from India.
Decades after the establishment of clear guidelines for management, mostly due to irrational approach, diarrhea is still a major concern in the developing world, including India. The scenario is even worse in urban slums owing to poor health-seeking and socio-environmental vulnerability. Determining the distribution of rational diarrhea management by practitioners and identification of its important predictors seemed urgent to minimize the potential for antibiotic resistance, diarrhea-related mortality and morbidity in these areas. Between May 2011 and January 2012, 264 consenting, randomly selected qualified and non-qualified practitioners (including pharmacists) were interviewed in the slums of Kolkata, a populous city in eastern India, regarding their characteristics, diarrhea-related knowledge (overall and in six separate domains: signs/symptoms, occurrence/spread, management, prevention/control, cholera and ORS), prescribed antibiotics, intravenous fluid (IVF) and laboratory investigations. Rationality was established based on standard textbooks. Among participants, 53.03% had no medical qualifications, 6.06% were attached to Governmental hospitals, 19.32% had best knowledge regarding diarrhea. While treating diarrhea, 7.20%, 17.80% and 20.08% respectively advised antibiotics, IVF and laboratory tests rationally. Logistic regression revealed that qualified and Governmental-sector practitioners managed diarrhea more rationally. Having best diarrhea-related knowledge regarding signs/symptoms (OR=5.49, p value=0.020), occurrence/spread (OR=3.26, p value=0.035) and overall (OR=6.82, p value=0.006) were associated with rational antibiotic prescription. Rational IVF administration was associated with best knowledge regarding diarrheal signs/symptoms (OR=3.00, p value=0.017), occurrence/spread (OR=3.57, p value=0.004), prevention/control (OR=4.89, p value=0.037), ORS (OR=2.55, p value=0.029) and overall (OR=4.57, p value<0.001). Best overall (OR=2.68, p value=0.020) and cholera-related knowledge (OR=2.34, p value=0.019) were associated with rational laboratory testing strategy. Diarrheal management practices were unsatisfactory in urban slums where practitioners' knowledge was a strong predictor for rational management. Interventions targeting non-qualified, independent practitioners to improve their diarrhea-related knowledge seemed to be required urgently to ensure efficient management of diarrhea in these endemic settings.


Use of cleansing agents at the peritoneal catheter exit site.
Heavy bacterial colonization results in exit-site infection. Antiseptic and non antiseptic agents have both been used for exit-site cleansing. An ideal cleansing agent should not only reduce the number of microorganisms, but should also be harmless to the body's defenses and should not interfere with wound healing. In vitro studies using animal cells have demonstrated that some antiseptic agents have adverse effects on wound healing. Strong cytotoxic antiseptics should be discouraged in exit-site cleansing. In choosing an appropriate cleansing agent for exitsite care, the phase of wound healing, the condition of the exit site, and the goal of cleansing should be taken into consideration. Antimicrobial soap is recommended for cleansing a healed exit site, but biocompatible solution is preferred for the postoperative, infected, or traumatized exit site. In vivo studies on the effectiveness of some cleansing agents are still lacking, and clinical study of exit-site cleansing is needed to determine the most effective agents for the task.


What are the health benefits of physical activity in type 1 diabetes mellitus? A literature review.
Physical activity improves well-being and reduces the risk of heart disease, cancer and type 2 diabetes mellitus in the general population. In individuals with established type 2 diabetes, physical activity improves glucose and lipid levels, reduces weight and improves insulin resistance. In type 1 diabetes mellitus, however, the benefits of physical activity are less clear. There is poor evidence for a beneficial effect of physical activity on glycaemic control and microvascular complications, and significant risk of harm through hypoglycaemia. Here we review the literature relating to physical activity and health in type 1 diabetes. We examine its effect on a number of outcomes, including glycaemic control, lipids, blood pressure, diabetic complications, well-being and overall mortality. We conclude that whilst there is sufficient evidence to recommend physical activity in the management of type 1 diabetes, it is still unclear as to what form, duration and intensity should be recommended and whether there is benefit for many of the outcomes examined.


Comparison between the ASSET EZ4 NCO and Impinger Sampling Devices for Aerosol Sampling of 4,4'-Methylene Diphenyl Diisocyanate in Spray Foam Application.
4,4'-methylene diphenyl diisocyanate (MDI) aerosol exposure evaluation in spray foam insulation application is known to be a challenge. Current available techniques are either not user-friendly or are inaccurate or are not validated for this application. A new sampler has recently been developed to address the user-friendliness issues with other samplers: the ASSET EZ4-NCO, but the use of this sampler in spray foam insulation applications has not been demonstrated or validated. Because of this, the current work was undertaken to provide a comparison of the ASSET sampler with an impinger method, considered to be the best available method in the context of spray foam insulation, and hence the pertinence of comparing this sampler to an impinger method, considered to be the best available method for measuring MDI monomer and oligomers for this particular application. Liquid chromatography coupled with tandem mass spectrometry method for MDI monomer and oligomer analysis was implemented based on the Supelco literature. It allows the analysis of MDI-dibutylamine (DBA) and MDI 3-ring-DBA with a minimum reported value of 5ng ml(-1), a dynamic range of 5-140ng ml(-1), precision <15% and accuracy >80%. This method was used to quantify MDI aerosols collected with the ASSET sampler in an MDI spray foam environment in parallel with the toluene/MOPIP impinger reference method. The ASSET sampler significantly underestimated the levels of MDI monomer and oligomers when compared to the reference method. The estimated bias was 72% (95% confidence interval [CI] 54-89%) for the monomer and 96% (95% CI 76-115%) for the oligomers. These results demonstrate the importance of evaluating each new sampler for each isocyanate application prior to a formal worker exposure evaluation.


[Clinical trial of aromatherapy on postpartum mother's perineal healing].
This study was designed to verify the effect of aromatherapy on a postpartum mother's perineal healing. The research design was a clinical trial. The methods of aromatherapy were applied sitz bath or soap application using essential oils with Lavender, Myrrh, Neroli, Rose, Grapefruit, Mandarin, Orange, and Roman Chamomile. The subjects of this experiment were postpartum mothers who delivered vaginally with an episiotomy. They were allocated to one of three groups; the aroma-sitz bath group, aroma-soap application group or control group. To evaluate the effect of aromatherapy, the perineal healing status was measured using the REEDA scale and smears of episiotomy wound were obtained. The data were analyzed by repeated measures of ANOVA, ANCOVA, chi2-test, and multiple response analysis via SPSS program. The REEDA scale was significantly low in the experimental group at postpartum 5th and 7th days (P=.009, P=.003), respectively. Most were observed 'few'(5-10 bacteria per field) bacteria in the smears of episiotomy wound. The one bacteria was identified in the 50.8% of subjects in pretest and two bacteria in the 60.3% in posttest. Most frequently identified bacteria were Escherichia coli and Enterococcus faecalis. In conclusion, these findings indicate that postpartum aromatherapy for perineal care could be effective in healing the perineum perineal care could be effective in healing the perineum.


Action of mibefradil and lacidipine on the isolated human anterior tibial artery.
In isolated human anterior tibial artery the effects of two different types of calcium channel antagonists, mibefradil (a selective T-type Ca2+ channel antagonist) and lacidipine (a 1,4 dihydropyridine Ca2+ channel antagonist, acting at L- and T-type, but binds preferentially at L-type Ca2+ channels) were compared. Both drugs reduced the contractions of isolated arteries induced by 60 mM KCl. The potency (IC50) of mibefradil was 6.5 microM and of lacidipine 82.4 nM. The potencies of both Ca2+ channel antagonists differed significantly (p<0.001 at 0.1 and 1 microM; p<0.01 at 10 microM). Lacidipine was 79-times more effective than mibefradil in reducing the vasoconstriction in isolated human anterior tibial artery. One of the reasons for higher potency of lacidipine could be a higher density of L-type than of T-type Ca2+ channels in tissue of the human anterior tibial artery.


Methyl violet: a selective agent for differentiation of Klebsiella pneumoniae from Enterobacter aerogenes and other gram-negative organisms.
Three selective media for differentiation of Klebsiella pneumoniae from Enterobacter aerogenes on the basis of colonial morphology were evaluated. Using methyl violet 2B as a selective agent, strains of K. pneumoniae isolated from urine, fresh water, and fresh produce were tested against other members of Enterobacteriaceae in addition to strains of Aeromonas hydrophila and Pseudomonas aeruginosa. Comparison of colonial morphology showed K. pneumoniae produced larger, smoother colonies than other bacteria tested. These media were developed to aid in presumptive separation of K. pneumoniae from E. aerogenes in the monitoring of bacterial quality of water.


[Soil respiration and carbon balance in wheat field under conservation tillage].
In order to study the characteristics of carbon sources and sinks in the winter wheat farmland ecosystem in southwest hilly region of China, the LI6400-09 respiratory chamber was adopted in the experiment conducted in the experimental field in Southwest University in Chongqing. The soil respiration and plant growth dynamics were analyzed during the growth period of wheat in the triple intercropping system of wheat-maize-soybean. Four treatments including T (traditional tillage), R (ridge tillage), TS (traditional tillage + straw mulching), and RS (ridge tillage + straw mulching) were designed. Root biomass regression (RR) and root exclusion (RE) were used to compare the contribution of root respiration to total soil respiration. The results showed that the average soil respiration rate was 1.71 micromol x (m2 x s)(-1) with a variation of 0.62-2.91 micromol x (m2 x s)(-1). Significant differences in soil respiration rate were detected among different treatments. The average soil respiration rate of T, R, TS and RS were 1.29, 1.59, 1.99 and 1.96 micromol x (m2 x s)(-1), respectively. R treatment did not increase the soil respiration rate significantly until the jointing stage. Straw mulching treatment significantly increased soil respiration, with a steadily high rate during the whole growth period. During the 169 days of growth, the total soil respiration was 2 266.82, 2799.52, 3 483.73 and 3 443.89 kg x hm(-2) while the cumulative aboveground biomasses were 51 800.84, 59 563.20, 66 015.37 and 7 1331.63 kg x hm(-2). Compared with the control, the yield of R, TS and RS increased by 14.99%, 27.44% and 37.70%, respectively. The contribution of root respiration to total soil respiration was 47.05% by RBR, while it was 53.97% by RE. In the early growth period, the carbon source was weak. The capacity of carbon sink started to increase at the jointing stage and reached the maximum during the filling stage. The carbon budget of wheat field was 5 924.512, 6743.807, 8350.741, 8 876.115 kg x hm(-2), respectively. The results indicated that ridge tillage and straw mulching conservation tillage significantly improved the carbon sink in the wheat farmland ecosystem.


Pharmacokinetics of potassium bromide in adult horses.
To determine the pharmacokinetics of potassium bromide (KBr) in horses after a single and multiple oral doses. Twelve adult Standardbred and Thoroughbred mares. Horses were randomly assigned into two treatment groups. In Part 1 of the study, horses were given a single oral dose of 120 mg/kg KBr. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of bromide were determined by colorimetric spectrophotometry following drug administration to permit determination of concentration versus time curves from which pharmacokinetic parameters could be calculated. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. Maximum mean serum bromide concentration following a single dose of KBr (120 mg/kg) was 284 +/- 15 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 days) gave a maximum serum bromide concentration of 1098 +/- 105 microg/mL. The administration of lower, maintenance doses of KBr (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 700 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. A loading dose of 120 mg/kg daily over 5 days and maintenance doses of approximately 90-100 mg/kg of KBr administered once daily are predicted to result in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.


Influenza surveillance in England and Wales: October 1995 to June 1996.
This report summarises information collected for the surveillance of influenza virus infection in England and Wales from October 1995 to June 1996 (weeks 40/95 to 25/96). Total respiratory disease' activity, as reported by the Birmingham Research Unit of the Royal College of General Practitioners, rose to peaks in weeks 48/95, 51/95, and 01/96. The first peak coincided with a peak in "influenza and flu-like illness'. The subsequent peaks were accounted for by an increase in reports of acute bronchitis, including bronchiolitis, and may have been associated with the annual rise in infections with respiratory syncytial virus. Influenza A virus was responsible for most infections, with moderate activity occurring in the early part of the winter, peaking in December (week 48/95). Influenza A subtype H3N2 predominated until week 07/96, after which subtype H1N1 accounted for most infections. Influenza activity was first seen in central and northern England, followed by the south of England, Wales, and Scotland. Circulating influenza viruses were antigenically similar to the components of the 1995/96 vaccine. International surveillance during 1995/96 has led to a different H3N2 component being included in the influenza vaccine recommended for 1996/97.


Biological effects of electromagnetic fields on insects: a systematic review and meta-analysis.
Worldwide, insects are declining at an alarming rate. Among other causes, the use of pesticides and modern agricultural practices play a major role in this. Cumulative effects of multiple low-dose toxins and the distribution of toxicants in nature have only started to be investigated in a methodical way. Existing research indicates another factor of anthropogenic origin that could have subtle harmful effects: the increasingly frequent use of electromagnetic fields (EMF) from man-made technologies. This systematic review summarizes the results of studies investigating the toxicity of electromagnetic fields in insects. The main objective of this review is to weigh the evidence regarding detrimental effects on insects from the increasing technological infrastructure, with a particular focus on power lines and the cellular network. The next generation of mobile communication technologies, 5G, is being deployed - without having been tested in respect of potential toxic effects. With humanity's quest for pervasiveness of technology, even modest effects of electromagnetic fields on organisms could eventually reach a saturation level that can no longer be ignored. An overview of reported effects and biological mechanisms of exposure to electromagnetic fields, which addresses new findings in cell biology, is included. Biological effects of non-thermal EMF on insects are clearly proven in the laboratory, but only partly in the field, thus the wider ecological implications are still unknown. There is a need for more field studies, but extrapolating from the laboratory, as is common practice in ecotoxicology, already warrants increasing the threat level of environmental EMF impact on insects.


Detecting Congestive Heart Failure by Extracting Multimodal Features and Employing Machine Learning Techniques.
The adaptability of heart to external and internal stimuli is reflected by the heart rate variability (HRV). Reduced HRV can be a predictor of negative cardiovascular outcomes. Based on the nonlinear, nonstationary, and highly complex dynamics of the controlling mechanism of the cardiovascular system, linear HRV measures have limited capability to accurately analyze the underlying dynamics. In this study, we propose an automated system to analyze HRV signals by extracting multimodal features to capture temporal, spectral, and complex dynamics. Robust machine learning techniques, such as support vector machine (SVM) with its kernel (linear, Gaussian, radial base function, and polynomial), decision tree (DT), k-nearest neighbor (KNN), and ensemble classifiers, were employed to evaluate the detection performance. Performance was evaluated in terms of specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). The highest performance was obtained using SVM linear kernel (TA = 93.1%, AUC = 0.97, 95% CI [lower bound = 0.04, upper bound = 0.89]), followed by ensemble subspace discriminant (TA = 91.4%, AUC = 0.96, 95% CI [lower bound 0.07, upper bound = 0.81]) and SVM medium Gaussian kernel (TA = 90.5%, AUC = 0.95, 95% CI [lower bound = 0.07, upper bound = 0.86]). The results reveal that the proposed approach can provide an effective and computationally efficient tool for automatic detection of congestive heart failure patients.


Comparison of characteristics of opioid-using pregnant women in rural and urban settings.
Historically, research on opioid use during pregnancy has occurred in urban settings and it is unclear how urban and rural populations compare. We examined socio-demographic and other variables in opioid-using pregnant women seeking treatment and screened for participation in a multi-site randomized controlled trial. Women screened in rural Burlington, Vermont (n = 54), were compared to those screened in urban Baltimore, Maryland (n = 305). Rural opioid-using pregnant women appear to have some characteristics associated with better treatment outcomes (e.g., less severe drug use, greater employment). However, they may face additional barriers in accessing treatment (e.g., greater distance from treatment clinic).


Octogenarians develop infrapopliteal arterial occlusive disease in the absence of traditional risk factors.
With increasing longevity, a growing proportion of patients who present with lower extremity peripheral arterial disease (LE-PAD) are ≥80 years old. While smoking and diabetes mellitus (DM) have traditionally been the main risk factors associated with PAD, we noted a pattern of severe infrapopliteal PAD in patients ≥80 years old in the absence of these traditional risk factors. As recognition of patterns of disease affects decisions regarding diagnostic and therapeutic approach, we sought to confirm this observation. A single-center retrospective review was performed on all patients who underwent lower extremity arteriography between March 2007 and September 2009. Arteriograms were scored in a blinded fashion. Any infrapopliteal PAD was defined as one or more infrapopliteal arteries with either >50% stenosis or total occlusion. Severe infrapopliteal PAD was defined as 2 or more infrapopliteal arteries with >50% stenosis or total occlusion. Fisher's exact test and 2-sample t-test or Wilcoxon rank-sum test were used for analysis. Two hundred ninety-seven patients comprised the study population. Eighty-two percent (= 145/176) of those ≤70 years old versus 96% (= 46/48) of those ≥80 years old had any infrapopliteal PAD (P = 0.02). Thirty percent of patients ≥80 years old with infrapopliteal PAD had no history of DM or smoking, while only 5% of younger patients had infrapopliteal PAD in the absence of DM or smoking (P < 0.0001). A similar pattern was seen for severe infrapopliteal PAD. Tissue loss was an indication for lower extremity arteriography in 45% of those ≤70 years of age versus 65% of those ≥80 (P = 0.022). A significant proportion of patients ≥80 years of age with PAD develop arterial disease in the infrapopliteal pattern in the absence of the traditional risk factors of smoking and DM. Our data also showed that this pattern of disease is significantly associated with tissue loss and critical limb ischemia, particularly in patients ≥80 years of age. Primary care providers need to be educated to suspect ischemic etiology for foot pain and ulcers in elderly patients not otherwise thought to have risk factors associated with PAD. Vascular specialists need to anticipate this pattern of disease when planning interventions. As smoking becomes less prevalent and as the population ages, octogenarians with severe infrapopliteal arterial occlusive disease will become a larger proportion of the patients treated by vascular specialists.


An approach to probe some neural systems interaction by functional MRI at neural time scale down to milliseconds.
In this paper, we demonstrate an approach by which some evoked neuronal events can be probed by functional MRI (fMRI) signal with temporal resolution at the time scale of tens of milliseconds. The approach is based on the close relationship between neuronal electrical events and fMRI signal that is experimentally demonstrated in concurrent fMRI and electroencephalographic (EEG) studies conducted in a rat model with forepaw electrical stimulation. We observed a refractory period of neuronal origin in a two-stimuli paradigm: the first stimulation pulse suppressed the evoked activity in both EEG and fMRI signal responding to the subsequent stimulus for a period of several hundred milliseconds. When there was an apparent site-site interaction detected in the evoked EEG signal induced by two stimuli that were primarily targeted to activate two different sites in the brain, fMRI also displayed signal amplitude modulation because of the interactive event. With visual stimulation using two short pulses in the human brain, a similar refractory phenomenon was observed in activated fMRI signals in the primary visual cortex. In addition, for interstimulus intervals shorter than the known latency time of the evoked potential induced by the first stimulus ( approximately 100 ms) in the primary visual cortex of the human brain, the suppression was not present. Thus, by controlling the temporal relation of input tasks, it is possible to study temporal evolution of certain neural events at the time scale of their evoked electrical activity by noninvasive fMRI methodology.


Sky island bird populations isolated by ancient genetic barriers are characterized by different song traits than those isolated by recent deforestation.
Various mechanisms of isolation can structure populations and result in cultural and genetic differentiation. Similar to genetic markers, for songbirds, culturally transmitted sexual signals such as breeding song can be used as a measure of differentiation as songs can also be impacted by geographic isolation resulting in population-level differences in song structure. Several studies have found differences in song structure either across ancient geographic barriers or across contemporary habitat barriers owing to deforestation. However, very few studies have examined the effect of both ancient barriers and recent deforestation in the same system. In this study, we examined the geographic variation in song structure across six populations of the White-bellied Shortwing, a threatened and endemic songbird species complex found on isolated mountaintops or "sky islands" of the Western Ghats. While some sky islands in the system are isolated by ancient valleys, others are separated by deforestation. We examined 14 frequency and temporal spectral traits and two syntax traits from 835 songs of 38 individuals across the six populations. We identified three major song clusters based on a discriminant model of spectral traits, degree of similarity of syntax features, as well as responses of birds to opportunistic playback. However, some traits like complex vocal mechanisms (CVM), relating to the use of syrinxes, clearly differentiated both ancient and recently fragmented populations. We suggest that CVMs may have a cultural basis and can be used to identify culturally isolated populations that cannot be differentiated using genetic markers or commonly used frequency-based song traits. Our results demonstrate the use of bird songs to reconstruct phylogenetic groups and impacts of habitat fragmentation even in complex scenarios of historic and contemporary isolation.


Single-file electrophoretic transport and counting of individual DNA molecules in surfactant nanotubes.
We demonstrate a complete nanotube electrophoresis system (nanotube radii in the range of 50 to 150 nm) based on lipid membranes, comprising DNA injection, single-molecule transport, and single-molecule detection. Using gel-capped electrodes, electrophoretic single-file transport of fluorescently labeled dsDNA molecules is observed inside nanotubes. The strong confinement to a channel of molecular dimensions ensures a detection efficiency close to unity and identification of DNA size from its linear relation to the integrated peak intensity. In addition to constituting a nanotechnological device for identification and quantification of single macromolecules or biopolymers, this system provides a method to study their conformational dynamics, reaction kinetics, and transport in cell-like environments.


Efficacy of combined liman peloid baths and heliotherapy in the treatment of psoriasis at Cervia spa, Emilia, Italy.
This study assessed the effects of liman peloid, followed by bath and heliotherapy in psoriatic patients at Cervia, Emilia, Italy. The psoriatic patients were randomized into two groups: group 1 with 56 patients, treated with liman applications, bath, and heliotherapy, and group 2 with 35 subjects, treated with mud-bath therapy using a clay peloid mixed with tap water and heliotherapy. Data was collected for the following: psoriasis area and severity index (PASI); delta-PASI (difference between post- and pre-treatment PASI); delta-PASI3 and delta-PASI6, 3 and 6 months after the end of treatment, respectively; psoriasis recurrences; and the use of both topical and systemic drugs. Although not significant, a decrease in PASI was recorded in group 1 at the end of treatment and after 3 and 6 months. Compared with group 2, there was a significant change in delta-PASI, delta-PASI3, and psoriasis recurrences in group 1 as well as a significant reduction in the topical use of drugs, both cortisone and nonsteroid drugs. This is the first and preliminary study which documented the efficacy of a specific protocol of liman bath heliotherapy in psoriatic patients as documented by a reduction in delta-PASI and delta-PASI3, a decrease in psoriasis recurrences, and use of topical drugs.


Inferring genes that escape X-Chromosome inactivation reveals important contribution of variable escape genes to sex-biased diseases.
The X Chromosome plays an important role in human development and disease. However, functional genomic and disease association studies of X genes greatly lag behind autosomal gene studies, in part owing to the unique biology of X-Chromosome inactivation (XCI). Because of XCI, most genes are only expressed from one allele. Yet, ∼30% of X genes "escape" XCI and are transcribed from both alleles, many only in a proportion of the population. Such interindividual differences are likely to be disease relevant, particularly for sex-biased disorders. To understand the functional biology for X-linked genes, we developed X-Chromosome inactivation for RNA-seq (XCIR), a novel approach to identify escape genes using bulk RNA-seq data. Our method, available as an R package, is more powerful than alternative approaches and is computationally efficient to handle large population-scale data sets. Using annotated XCI states, we examined the contribution of X-linked genes to the disease heritability in the United Kingdom Biobank data set. We show that escape and variable escape genes explain the largest proportion of X heritability, which is in large part attributable to X genes with Y homology. Finally, we investigated the role of each XCI state in sex-biased diseases and found that although XY homologous gene pairs have a larger overall effect size, enrichment for variable escape genes is significantly increased in female-biased diseases. Our results, for the first time, quantitate the importance of variable escape genes for the etiology of sex-biased disease, and our pipeline allows analysis of larger data sets for a broad range of phenotypes.


Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis.
Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown. To explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema. This prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022. Duration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death. Incidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score-weighted Cox proportional hazards regression models. Of 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78). In this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.


Joint Associations of Maternal Gestational Diabetes and Hypertensive Disorders of Pregnancy With Overweight in Offspring.
Objectives: Either maternal gestational diabetes mellitus (GDM) or hypertensive disorder of pregnancy (HDP) is associated with an increased risk of obesity in the offspring. However, their joint associations with obesity in offspring remain unclear. We investigated the joint associations of maternal GDM and HDP with childhood overweight in offspring. Methods: We performed a large study in 1967 mother-child pairs. Maternal GDM was diagnosed according to the 1999 World Health Organization (WHO) criteria. HDP was defined as self-reported doctor-diagnosed hypertension or treatment of hypertension (including gestational hypertension, preeclampsia, sever preeclampsia or eclampsia) after 20 weeks of gestation on the questionnaire. Body mass index (BMI) for age Z-score and childhood overweight were evaluated according to WHO growth reference. We used the general linear models to compare children's Z score for BMI and logistic regression models to estimate odds ratios of childhood overweight according to maternal different status of GDM and HDP. Results: Offspring of mothers with both GDM and HDP had a higher BMI for age Z-score (0.63 vs. 0.03, P < 0.001) than children born to normotensive and normoglycemic pregnancy. After adjustment for maternal and children's major confounding factors, joint GDM and HDP were associated with increased odds ratios of offspring's overweight compared with normotensive and normoglycemic pregnancy (2.97, 95% confidence intervals [CIs] 1.65-5.34) and GDM alone (2.06, 95% CIs 1.20-3.54), respectively. After additional adjustment for maternal pre-pregnancy BMI and gestational weight gain, joint maternal GDM, and HDP was still associated with an increased risk of offspring's overweight compared with the maternal normotensive, and normoglycemic group but became to have a borderline increased risk compared with the maternal GDM alone group. Conclusions: Maternal GDM alone or joint GDM and HDP were associated with increased ratios of offspring's overweight.


STAT1 signaling in CD8 T cells is required for their clonal expansion and memory formation following viral infection in vivo.
Recent advances have shown that direct type I IFN signaling on T cells is required for their efficient expansion in response to viral infections in vivo. It is not clear which intracellular signaling molecule is responsible for this effect. Although STAT1 has been shown to mediate many of the type I IFN-dependent biological effects, its role in T cells remains uncertain in vivo. In this study, we demonstrated that STAT1 signaling in CD8 T cells was required for their efficient expansion by promoting the survival of activated CD8 T cells upon vaccinia viral infection in vivo, suggesting that the direct effect of type I IFNs on CD8 T cells is mediated by STAT1. Furthermore, effector CD8 T cells that lack STAT1 signaling did not survive the contraction phase to differentiate into long-lived memory cells. These results identify a critical role for type I IFN-STAT1 signaling in multiple stages of CD8 T cell response in vivo and suggest that strategies to activate type I IFN-STAT1 signaling pathway may enhance vaccine potency.


Disrupted tRNA Genes and tRNA Fragments: A Perspective on tRNA Gene Evolution.
Transfer RNAs (tRNAs) are small non-coding RNAs with lengths of approximately 70-100 nt. They are directly involved in protein synthesis by carrying amino acids to the ribosome. In this sense, tRNAs are key molecules that connect the RNA world and the protein world. Thus, study of the evolution of tRNA molecules may reveal the processes that led to the establishment of the central dogma: genetic information flows from DNA to RNA to protein. Thanks to the development of DNA sequencers in this century, we have determined a huge number of nucleotide sequences from complete genomes as well as from transcriptomes in many species. Recent analyses of these large data sets have shown that particular tRNA genes, especially in Archaea, are disrupted in unique ways: some tRNA genes contain multiple introns and some are split genes. Even tRNA molecules themselves are fragmented post-transcriptionally in many species. These fragmented small RNAs are known as tRNA-derived fragments (tRFs). In this review, I summarize the progress of research into the disrupted tRNA genes and the tRFs, and propose a possible model for the molecular evolution of tRNAs based on the concept of the combination of fragmented tRNA halves.


Oxidation of the cyclic ethers 1,4-dioxane and tetrahydrofuran by a monooxygenase in two Pseudonocardia species.
The bacterium Pseudonocardia dioxanivorans CB1190 grows on the cyclic ethers 1,4-dioxane (dioxane) and tetrahydrofuran (THF) as sole carbon and energy sources. Prior transcriptional studies indicated that an annotated THF monooxygenase (THF MO) gene cluster, thmADBC, located on a plasmid in CB1190 is upregulated during growth on dioxane. In this work, transcriptional analysis demonstrates that upregulation of thmADBC occurs during growth on the dioxane metabolite β-hydroxyethoxyacetic acid (HEAA) and on THF. Comparison of the transcriptomes of CB1190 grown on THF and succinate (an intermediate of THF degradation) permitted the identification of other genes involved in THF metabolism. Dioxane and THF oxidation activity of the THF MO was verified in Rhodococcus jostii RHA1 cells heterologously expressing the CB1190 thmADBC gene cluster. Interestingly, these thmADBC expression clones accumulated HEAA as a dead-end product of dioxane transformation, indicating that despite its genes being transcriptionally upregulated during growth on HEAA, the THF MO enzyme is not responsible for degradation of HEAA in CB1190. Similar activities were also observed in RHA1 cells heterologously expressing the thmADBC gene cluster from Pseudonocardia tetrahydrofuranoxydans K1.


How Are Obesity and Body Composition Related to Patellar Cartilage? A Systematic Review.
The aim of this review was to systematically examine the evidence for an association between measures of obesity [weight and body mass index (BMI)] and body composition (fat mass and fat-free mass) and patellar cartilage, assessed using magnetic resonance imaging. Three electronic databases (MEDLINE, EMBASE, and CINAHL) were searched up to April 2016 using full text and MeSH terms to identify studies examining the associations between obesity and body composition, and patellar cartilage. Two independent reviewers extracted the data and assessed the methodological quality of included studies. Seventeen studies were included: 5 cross-sectional, 10 cohort studies measuring outcomes at 2 timepoints, and 2 longitudinal studies assessing outcome only at the timepoint. Eleven studies were of high or moderate quality. In asymptomatic middle-aged adults, elevated body weight and BMI were systematically associated with worse patellofemoral cartilage scores. There was more consistent evidence for patellar cartilage defects than patellar cartilage volume, particularly in women. Increased BMI was also consistently associated with increased cartilage loss in longitudinal studies, although not all attained statistical significance. There is a need for more high-quality research to confirm these findings and to better explain the relative contributions of metabolic and biomechanical factors to the initiation of patellofemoral osteoarthritis, to devise effective strategies to manage this common and disabling condition.


Studies on variants of Bacillus stearothermophilus strain NCA 1518.
The heat resistance, fermentation reactions, nutritional requirements, and phage sensitivity of 18 selected morphological variants of Bacillus stearothermophilus NCA 1518 were studied. It was found that when smooth variants mutated to rough colonial morphology, there was no concurrent change in fermentation reactions, nutritional requirements, or heat resistance. The smooth variant, and the rough mutants derived directly from it, presented a uniform pattern of biochemical capabilities which differed from the pattern presented by the rough variants isolated from the same stock culture. This led to the conclusion that the smooth and rough types previously observed in stocks of B. stearothermophilus NCA 1518 either were carried in the stock since the original isolation or represent a very profound and uncommon mutation, or that one of the variants has been introduced into the stock culture from an extraneous source sometime in the past.


High rates of albuminuria but not of low eGFR in urban indigenous Australians: the DRUID study.
Indigenous Australians have an incidence of end stage kidney disease 8-10 times higher than non-Indigenous Australians. The majority of research studies concerning Indigenous Australians have been performed in rural or remote regions, whilst the majority of Indigenous Australians actually live in urban settings. We studied prevalence and factors associated with markers of kidney disease in an urban Indigenous Australian cohort, and compared results with those for the general Australian population. 860 Indigenous adult participants of the Darwin Region Urban Indigenous Diabetes (DRUID) Study were assessed for albuminuria (urine albumin-creatinine ratio≥2.5 mg/mmol males, ≥3.5 mg/mmol females) and low eGFR (estimated glomular filtration rate < 60 mls/min/1.73 m(2)). Associations between risk factors and kidney disease markers were explored. Comparison was made with the AusDiab cohort (n = 8,936 aged 25-64 years), representative of the general Australian adult population. A high prevalence of albuminuria (14.8%) was found in DRUID, whilst prevalence of low eGFR was 2.4%. Older age, higher HbA1c, hypertension, higher C-reactive protein and current smoking were independently associated with albuminuria on multiple regression. Low eGFR was independently associated with older age, hypertension, albuminuria and higher triglycerides. Compared to AusDiab participants, DRUID participants had a 3-fold higher adjusted risk of albuminuria but not of low eGFR. Given the significant excess of ESKD observed in Indigenous versus non-Indigenous Australians, these findings could suggest either: albuminuria may be a better prognostic marker of kidney disease than low eGFR; that eGFR equations may be inaccurate in the Indigenous population; a less marked differential between Indigenous and non-Indigenous Australians for ESKD rates in urban compared to remote regions; or that differences in the pathophysiology of chronic kidney disease exist between Indigenous and non-Indigenous populations.


Epilepsy and mental retardation limited to females: an under-recognized disorder.
Epilepsy and Mental Retardation limited to Females (EFMR) which links to Xq22 has been reported in only one family. We aimed to determine if there was a distinctive phenotype that would enhance recognition of this disorder. We ascertained four unrelated families (two Australian, two Israeli) where seizures in females were transmitted through carrier males. Detailed clinical assessment was performed on 58 individuals, using a validated seizure questionnaire, neurological examination and review of EEG and imaging studies. Gene localization was examined using Xq22 microsatellite markers. Twenty-seven affected females had a mean seizure onset of 14 months (range 6-36) typically presenting with convulsions. All had convulsive attacks at some stage, associated with fever in 17 out of 27 (63%). Multiple seizure types occurred including tonic-clonic (26), tonic (4), partial (11), absence (5), atonic (3) and myoclonic (4). Seizures ceased at mean 12 years. Developmental progress varied from normal (7), to always delayed (4) to normal followed by regression (12). Intellect ranged from normal to severe intellectual disability (ID), with 67% of females having ID or being of borderline intellect. Autistic (6), obsessive (9) and aggressive (7) features were prominent. EEGs showed generalized and focal epileptiform abnormalities. Five obligate male carriers had obsessional tendencies. Linkage to Xq22 was confirmed (maximum lod 3.5 at = 0). We conclude that EFMR is a distinctive, under-recognized familial syndrome where girls present with convulsions in infancy, often associated with intellectual impairment and autistic features. The unique inheritance pattern with transmission by males is perplexing. Clinical recognition is straightforward in multiplex families due to the unique inheritance pattern; however, this disorder should be considered in smaller families where females alone have seizures beginning in infancy, particularly in the setting of developmental delay. In single cases, diagnosis will depend on identification of the molecular basis.


Micronutrient supplemented probiotic yogurt for HIV-infected adults taking HAART in London, Canada.
The Human Immunodeficiency Virus has devastating effects worldwide. The burden is less pronounced, but still present in Canada where approximately 64,000 men and women are HIV positive. The virus and the life-saving antiretroviral therapies often contribute to diarrhea and other gastrointestinal disturbances. Certain probiotic organisms, such as Lactobacillus rhamnosus GR-1, have been shown to alleviate diarrhea as well as delay the decline of CD4 lymphocytes in some subjects. In addition, micronutrient formulae have been used extensively among HIV positive persons as a cost-effective method for improving quality of life and immune function. The objective of the present study was to combine probiotics and micronutrients into an affordable and highly palatable nutritional supplement and assess outcomes in 21 HIV-positive participants receiving highly active antiretroviral therapy in London, Ontario, Canada. The design was a randomized, double blind, three-period, cross-over controlled trial with three different formulations of supplemented yogurt; micronutrient and probiotic (A), micronutrient alone (B) and probiotic alone (C). The period of intake for each of the types was 30 days with a 14 day wash-out period between the intervention types. The mean increase in CD4 was greatest with B (41 cells/µL, SD 221). Supplement A showed a mean change of +19 cells/µL (SD 142) and supplement C a mean change of - 7 cells/µL (SD 154). All yogurt types caused an increase in subjective energy and ability to perform daily activity scores. According to the safety measures taken to assess the tolerance of the yogurt, there were no adverse events and the yogurt was well-tolerated. These preliminary findings suggest that micronutrient supplemented probiotic yogurt may support immune function among people living with HIV.


Ten-day sequential treatment for Helicobacter pylori eradication in clinical practice.
Cure rates of Helicobacter pylori infection with standard triple therapy are disappointingly low. A very effective, new sequential treatment schedule has recently been described. However, all studies published to date were performed in Italy; it is mandatory to confirm these results in other settings. To assess the cure rate and the acceptability of a new sequential treatment regimen through a pilot study. A hundred and thirty-nine patients (60% men, mean age 49.6 +/- 15.7 yr) were recruited from six centers. H. pylori status was assessed by histology, urease test or urea breath test. Sequential regime consisted of a 10-day treatment including a proton pump inhibitor (PPI) b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by a PPI b.d. clarithromycin 500 mg b.d. and metronidazole 500 mg b.d for the next 5 days. Eradication was determined 8 wk after the end of treatment by urea breath test or histology. Eradication rates were calculated both per protocol and by intention-to-treat. Eradication was achieved in 117 out of 129 patients who returned for a follow-up test. The intention-to-treat eradication rate was thus 84.2% (95%CI: 77%-90%) and the per-protocol cure rate 90.7% (95%CI: 84%-95%). The treatment was well tolerated. Only 14 patients complained of mild side effects. Sequential treatment seems highly effective for eradicating H. pylori.


Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.
Pazopanib has shown clinical activity against multiple tumour types and is generally well tolerated. However, isolated elevations in transaminases and bilirubin have been observed. This study examined polymorphisms in molecules involved in pharmacokinetic and pharmacodynamic pathways of pazopanib and their association with hepatic dysfunction. Twenty-eight polymorphisms in 11 genes were evaluated in pazopanib-treated renal cell carcinoma patients. An exploratory analysis was conducted in 116 patients from a phase II study; a replication study was conducted in 130 patients from a phase III study. No polymorphisms were associated with alanine aminotransferase elevation. The Gilbert's uridine-diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1) TA-repeat polymorphism was significantly associated with pazopanib-induced hyperbilirubinemia in the phase II study. This association was replicated in the phase III study (P<0.01). Patients with TA6/TA6, TA6/TA7, and TA7/TA7 genotypes experienced median bilirubin increases of 0.31, 0.37, and 0.71 x upper limit of the normal range (ULN), respectively. Of the 38 patients with hyperbilirubinemia (> or = 1.5 x ULN), 32 (84%) were either TA7 homozygotes (n=18) or TA7 heterozygotes (n=14). For TA7 homozygotes, the odds ratio (95% CI) for developing hyperbilirubinemia was 13.1 (5.3-32.2) compared with other genotypes. The UGT1A1 polymorphism is frequently associated with pazopanib-induced hyperbilirubinemia. These data suggest that some instances of isolated hyperbilirubinemia in pazopanib-treated patients are benign manifestations of Gilbert's syndrome, thus supporting continuation of pazopanib monotherapy in this setting.


Validity of Estimated Acrylamide Intake by the Dietary Record Method and Food Frequency Questionnaire in Comparison with a Duplicate Method: A Pilot Study.
Acrylamide, classified as a probable carcinogen to humans, forms during high- temperature cooking. Dietary exposure among the Japanese is unknown. To evaluate the validity of estimated acrylamide intake using a dietary record (DR) and the food frequency questionnaire (FFQ) in comparison with the duplicate diet method (DM) in a Japanese population. Design: A validation study was performed with 14 participants (age, 32-50 y; 11 women) from 11 households. Food samples were simultaneously collected for the DM and DR on the same day over 2 consecutive days. The FFQ was administered after collecting samples for the DM and DR. For the DM, dietary acrylamide was calculated from chemical analyses of each food. For the DR and FFQ, acrylamide intake for each food was calculated using the database of acrylamide contents of foods. Correlation coefficients were calculated using the Spearman rank method. Average acrylamide intake values calculated using the DM, DR, and FFQ were 0.106, 0.233, and 0.128 μg/kg body weight/d, respectively; these values showed a marginally positive correlation between the DM and DR (r=0.52), but a low correlation between the DM and FFQ (r=-0.011). For the DR, non-alcoholic drinks had the highest contribution, followed by confectionery and vegetables. For the DM, the contribution of confectionery was the highest, followed by vegetables and non-alcoholic drinks. In conclusion, the validity of acrylamide intake estimation using the DR was reasonably high when compared to the analytical value of the simultaneous DM. However, further improvement is required for estimating acrylamide intake using the FFQ.


LncRNA SNHG11 induces ferroptosis in liver injury cells through miR-324-3p/GPX4 axis-mediated sepsis.
Sepsis is a kind of systemic inflammatory response syndrome caused by infection, which has high morbidity and mortality. Studies have shown that reducing sepsis-related liver injury and restoring liver function can reduce the morbidity and mortality of it. Current clinical treatment methods for sepsis have many disadvantages. Our study aimed to investigate the mechanism of sepsis-induced liver injury and to find a proper therapeutic target for sepsis. In this paper, we have found that when miR-324-3p was overexpressed, the inflammatory infiltration and and ferroptosis in liver injury cells aggravated. Further studies showed that overexpression of miR-324-3p could bind to the 3'-UTR of SNHG11 directly so as to decrease the expression level of SNHG11. Our study indicated that LncRNA SNGH11 can mediate the ferroptosis of liver injury cells induced by sepsis through the miR-324-3p/GPX4 axis. Suggesting that it is a new drug target for clinical treatment of sepsis and sepsis-associated liver injury, then we can improve the survival rate for sepsis patients.


Magnopyramidal neurons in the anterior motor speech region. Dendritic features and interhemispheric comparisons.
To test the hypothesis that the larger somal size of layer III magnopyramidal neurons in left than in right Brodmann area 45 is associated with greater measures of dendritic arborization in the left hemisphere neurons. A case series involving postmortem human brain specimens was used to compare dendritic parameters of Golgi-impregnated layer III pyramidal neurons in Brodmann area 45 in the left and right hemispheres. A convenience sample consisting of 9 subjects with no known neurologic or psychiatric disorders was obtained at autopsy. Dendritic parameters of the 10 largest Golgi-impregnated layer III pyramidal neurons were measured in each hemisphere of each brain using a eutectic neuron tracing system. The measures examined were somal size, neuron depth, mean segment length, number of branch points, maximal branch order, combined dendritic diameter, total dendritic length, horizontal extent of the dendritic field, and spine density. The Golgi-impregnated slides were also compared with Nissl-stained slides from adjacent blocks to determine the laminar location of the sampled neurons. Although the mean somal size was greater in the left than in the right hemisphere, none of the dendritic parameters examined was larger for the left hemisphere neurons. As expected, total dendritic length was positively correlated to somal size (r = 0.43, P < 001) in the left hemisphere. However, there was no correlation between these parameters in the right hemisphere (r = 0.02, P = .76). The difference between left and right Brodmann area 45 magnopyramidal neurons in the correlation of somal size and dendritic length provides additional evidence of anatomical differences between these 2 populations of neurons. However, the lack of interhemispheric differences in measures of dendritic arborization suggests that additional factors contribute significantly to the marked difference in somal size between the large magnopyramidal neurons in the left and right hemispheres.


High capacity hydrogen storage materials: attributes for automotive applications and techniques for materials discovery.
Widespread adoption of hydrogen as a vehicular fuel depends critically upon the ability to store hydrogen on-board at high volumetric and gravimetric densities, as well as on the ability to extract/insert it at sufficiently rapid rates. As current storage methods based on physical means--high-pressure gas or (cryogenic) liquefaction--are unlikely to satisfy targets for performance and cost, a global research effort focusing on the development of chemical means for storing hydrogen in condensed phases has recently emerged. At present, no known material exhibits a combination of properties that would enable high-volume automotive applications. Thus new materials with improved performance, or new approaches to the synthesis and/or processing of existing materials, are highly desirable. In this critical review we provide a practical introduction to the field of hydrogen storage materials research, with an emphasis on (i) the properties necessary for a viable storage material, (ii) the computational and experimental techniques commonly employed in determining these attributes, and (iii) the classes of materials being pursued as candidate storage compounds. Starting from the general requirements of a fuel cell vehicle, we summarize how these requirements translate into desired characteristics for the hydrogen storage material. Key amongst these are: (a) high gravimetric and volumetric hydrogen density, (b) thermodynamics that allow for reversible hydrogen uptake/release under near-ambient conditions, and (c) fast reaction kinetics. To further illustrate these attributes, the four major classes of candidate storage materials--conventional metal hydrides, chemical hydrides, complex hydrides, and sorbent systems--are introduced and their respective performance and prospects for improvement in each of these areas is discussed. Finally, we review the most valuable experimental and computational techniques for determining these attributes, highlighting how an approach that couples computational modeling with experiments can significantly accelerate the discovery of novel storage materials (155 references).


Eye movement-invariant representations in the human visual system.
During natural vision, humans make frequent eye movements but perceive a stable visual world. It is therefore likely that the human visual system contains representations of the visual world that are invariant to eye movements. Here we present an experiment designed to identify visual areas that might contain eye-movement-invariant representations. We used functional MRI to record brain activity from four human subjects who watched natural movies. In one condition subjects were required to fixate steadily, and in the other they were allowed to freely make voluntary eye movements. The movies used in each condition were identical. We reasoned that the brain activity recorded in a visual area that is invariant to eye movement should be similar under fixation and free viewing conditions. In contrast, activity in a visual area that is sensitive to eye movement should differ between fixation and free viewing. We therefore measured the similarity of brain activity across repeated presentations of the same movie within the fixation condition, and separately between the fixation and free viewing conditions. The ratio of these measures was used to determine which brain areas are most likely to contain eye movement-invariant representations. We found that voxels located in early visual areas are strongly affected by eye movements, while voxels in ventral temporal areas are only weakly affected by eye movements. These results suggest that the ventral temporal visual areas contain a stable representation of the visual world that is invariant to eye movements made during natural vision.


Relationships between adenosine and coronary resistance in conscious exercising dogs.
The relation between myocardial adenosine content, coronary sinus plasma concentration, and coronary vascular resistance was studied in conscious dogs during rest or treadmill exercise. Exercise at 5 mi/h for 7 min on a 20% slope had a significant threefold increase in cardiac work over that of dogs at rest. Exercise increased myocardial adenosine content from 1.35 +/- 0.54 to 8.18 +/- 0.60 nmol/g and decreased coronary vascular resistance from 1.07 +/- 0.13 to 0.69 +/- 0.08 mmHg.ml-1.min.100 g; the former correlated negatively with the latter (r = -0.74, P less than 0.01). The adenosine concentration in coronary sinus plasma increased from 108 +/- 16 to 184 +/- 18 nmol/l plasma and correlated negatively with coronary vascular resistance (r = -0.83, P less than 0.01). Myocardial adenosine content correlated positively with coronary sinus plasma adenosine concentration (r = 0.77, P less than 0.05). Low myocardial lactate content, continued lactate uptake, lack of change in the lactate-pyruvate ratio, and stable coronary sinus oxygen tension values indicated no myocardial hypoxia. These findings demonstrate the release of adenosine into coronary sinus blood and show significant correlations between myocardial adenosine content, coronary sinus adenosine concentration, and coronary vascular resistance during physiological exercise in the dog. The results support the hypothesis that adenosine regulates coronary blood flow during increased metabolic activity.


Effect of reductones on glyoxalase I1.
The effect of some reductones on glyoxalase I prepared from animal and microbial origins has been studied. The enzyme was extracted from ox liver or baker's yeast and partially purified by ammonium sulfate fractionation, gel filtration and ion exchange chromatography. Aliphatic reductones such as ascorbic acid, ascorbic acid 3-phosphate and triose reductone showed strong to medium inhibition, while dehydroascorbic acid showed no inhibition. Kinetic analysis indicated that the inhibition mechanism of ascorbic acid was uncompetitive. Varying extents of inhibition were observed among three kinds of diphenols belonging to aromatic reductones. They were in the order of increasing inhibitory power resorcinol, hydroquinone and catechol for the ox liver enzyme, and catechol, resorcinol and hydroquinone for the yeast enzyme. p-Benzoquinone, an oxidized reductone, exhibited marked inhibition on both enzymes. Its action seemed due to reaction with amino and/or sulfhydryl functions of enzyme protein and those of glutathione, one of the substrates.


Progression of gait disorder and rigidity and risk of death in older persons.
Bradykinesia, gait disturbance, rigidity, and tremor are common motor signs in old age. All of these signs are associated with increased morbidity and mortality, but the extent to which they are progressive is unknown. Study participants were 787 older Catholic clergy members without clinically diagnosed PD, related conditions, or dementia at baseline. They were evaluated annually for up to 7 years, with >95% follow-up participation by survivors. Evaluations included administration of a modified version of the motor portion of the Unified PD Rating Scale (UPDRS), from which previously established measures of the global UPDRS and four specific motor signs were derived. Scores represent the percent of the total possible UPDRS score obtained. At baseline, the global UPDRS score ranged from 0 to 36.3 (mean +/- SD, 7.3 +/- 6.4). It increased by an average of 0.69 unit per year during follow-up, with more rapid progression in older persons, but there was wide variability with no progression in 21% of subjects and annual increases of up to 8.23 units in the remaining 79%. Of 129 persons who died, 106 had follow-up UPDRS data. In a proportional hazards model, risk of death was associated with both the level of the global UPDRS score at baseline and the annual rate of progression (both p < 0.001). Overall, risk of death in subjects who had some worsening of the global UPDRS score was 2.93 times the rate among those without progression (95% CI, 1.32-6.50). Gait disorder/postural reflex impairment and rigidity worsened, but bradykinesia and tremor did not. Risk of death was associated with worsening of gait/posture but not with the other signs. Gait disorder and rigidity, as assessed with the modified UPDRS, are usually progressive in old age. Both the severity of the gait disorder and its rate of progression are strongly associated with risk of death.


Multiple myeloma exploits Jagged1 and Jagged2 to promote intrinsic and bone marrow-dependent drug resistance.
Multiple myeloma is still incurable due to an intrinsic aggressiveness or, more frequently, to the interactions of malignant plasma cells with the bone marrow (BM) microenvironment. Myeloma cells educate BM cells to support neoplastic cell growth, survival, acquisition of drug resistance resulting in disease relapse. Myeloma microenvironment is characterized by Notch signaling hyperactivation due to the increased expression of Notch1 and 2 and the ligands Jagged1 and 2 in tumor cells. Notch activation influences myeloma cell biology and promotes the reprogramming of BM stromal cells. In this work we demonstrate, in vitro, ex vivo and by using a zebrafish multiple myeloma model, that Jagged inhibition causes a decrease in both myeloma-intrinsic and stromal cell-induced resistance to currently used drugs, i.e. bortezomib, lenalidomide and melphalan. The molecular mechanism of drug resistance involves the chemokine system CXCR4/SDF1α. Myeloma cell-derived Jagged ligands trigger Notch activity in BM stromal cells. These, in turn, secrete higher levels of SDF1α in the BM microenvironment increasing CXCR4 activation in myeloma cells, which is further potentiated by the concomitant increased expression of this receptor induced by Notch activation. Consistently with the augmented pharmacological resistance, SDF1α boosts the expression of BCL2, Survivin and ABCC1. These results indicate that a Jagged-tailored approach may contribute to disrupting the pharmacological resistance due to intrinsic myeloma cell features or to the pathological interplay with BM stromal cells and, conceivably, improve patients' response to standard-of-care therapies.


Msx1 and Msx2 in limb mesenchyme modulate digit number and identity.
Msx1 and Msx2 encode homeodomain transcription factors that play a crucial role in limb development. However, the limb phenotype of the double Msx1(null/null) Msx2(null/null) mutant is difficult to analyze, particularly along the anteroposterior axis, because of the complex effects of the double mutation on both ectoderm- and mesoderm-derived structures. Namely, in the mutant, formation of the apical ectodermal ridge (AER) is impaired anteriorly and, consequently, the subjacent mesenchyme does not form. Using the Cre/loxP system, we investigated the respective roles of Msx genes in ectoderm and mesoderm by generating conditional mutant embryos with no Msx activity solely in the mesoderm. In these mutants, the integrity of the ectoderm-derived AER was maintained, allowing formation of the anterior mesenchyme. With this strategy, we demonstrate that mesenchymal expression of Msx1 and Msx2 is required for proper Shh and Bmp4 signaling to specify digit number and identity.


Socio-cultural factors affecting the spread of HIV/AIDS in Africa: a case study.
There is a disproportionate share of AIDS cases over the years in Africa. This has occurred in racial and ethnic minority populations, a finding likely related to social, economic and cultural factors. Certain socio-cultural and religious practices such as polygamy and giving a daughter away in marriage without considering the social life of the man are likely contributory factors to the higher prevalence of HIV/AIDS in women in this part of the world. This is illustrated with a case of Mr. M. S. who married two wives within four months interval, having lived a promiscuous life before marriage. One of the wives was a virgin at the time of marriage. Neither of wives had any symptoms suggestive of STD or HIV before marriage, however, the three of them tested positive to HIV-1 following a visit to the special treatment clinic. He had genital herpes and his two wives also had vulvovaginal candidiasis, genital herpes and condyloma accuminata (genital warts). The husband would not want his HIV status declared to the wives. There is therefore a need to enact law on pre-marriage HIV screening for intending couples. Couple Pre-and post-test counseling must be encouraged and promoted. In addition, women should be empowered to negotiate safer sex.


Giving Voice to Silence: Empowerment and Disempowerment in the Developmental Shift from Trauma 'Victim' to 'Survivor-Advocate'.
In the past several years, a public conversation in the United States about interpersonal violence has flourished, sustained by the work of advocates who are themselves survivors. This surge in public sharing of trauma stories is a rhetorical form of resistance to ideologies in mainstream American culture that impose silence on survivors (e.g., the "just world" belief). However, the developmental progression from trauma 'victim' to empowered public 'survivor/advocate' accommodates to dominant American cultural preferences that stories of adversity have a redemptive story line. In a redemptive story, negative experiences are followed by something positive (e.g., personal growth, lessons learned, strength gained). In this paper, we draw from theory and the sparse relevant literature across multiple disciplines to conceptualize when and for whom the redemptive storying of trauma (or, redemptive master narrative) is available, advantageous, and systemically encouraged. Among the proposed advantages of redemptive storying are its psychological health benefits; potential to empower self and others; promotion of meaning-making, mission, and communal solidarity; and the larger social/political changes that can emerge from giving voice to silenced experiences. Proposed challenges to redemptive storying include layers of societal oppression and marginalization that shape the redemption stories of many survivor-advocates; ongoing connection to or dependence on relationships and communities that enable abuse; and the reality of historical trauma and other forms of intergenerational trauma, which complicate the linear, individualistic story of redemption. With this theory-driven framework, we wish to promote compassion for survivors, along with interdisciplinary, inclusive, and intersectional research in this understudied area.


The Association of Emotional Support, HIV Stigma, and Home Environment With Disclosure Efficacy and Perceived Disclosure Outcomes in Young People Living With HIV in Zambia: A Cross-Sectional Study.
This study examined the association of various forms of social support, attitudes toward living at home, and HIV stigma experiences with HIV self-disclosure efficacy and perceived negative disclosure outcomes. We analyzed cross-sectional data from 120 young people with HIV (YPWH) aged 18-21 years receiving outpatient care in Eastern Province, Zambia. Perceived negative disclosure outcomes and disclosure self-efficacy were measured using an adapted version of the Adolescent HIV Disclosure Cognitions and Affect Scale. Explanatory variables included parental or caregiver support, emotional support, instrumental support, HIV stigma experiences, and attitudes toward living at home. Findings suggest that YPWH's confidence in their ability to self-disclose their HIV status and their assessment of negative outcomes associated with HIV disclosure are influenced by emotional support, experiences of HIV stigma, and the quality of the home environment.


Mortality in an insured population with atrial fibrillation.
In a cooperative study of 3,099 life insurance applicants with atrial fibrillation (AF), 71 deaths over an average duration of 3.3 years were observed and compared with deaths expected and derived from standard insurance mortality tables. A normal mortality was observed in cases of paroxysmal AF with no other identified cardiovascular impairment. Paroxysmal AF with associated mitral stenosis or coronary disease was found to have a significantly increased mortality. Chronic AF with or without other impairments entails a much higher risk than paroxysmal AF, those cases associated with mitral stenosis showing very high excess mortality.


[Not Available].
S. Gouy, C. Uzan, Y. Zafrani, C. Lhommé, P. Pautier, P. Duvillard, C. Haie-Meder, P. Morice Uterine cancer can metastasize to both the pelvic and para-aortic levels. No one questions the diagnostic and prognostic value of lymphadenectomy, but its therapeutic value is still open to debate. In early cervical cancer (<4 cm.), pelvic lymphadenectomy is a routine part of radical hysterectomy. If pelvic lymph nodes show involvement, one can propose an extension of the lymphadenectomy to the para-aortic level. Studies of sentinel lymph node identification and biopsy at this level are currently under way. The standard treatment of cervical cancer > 4 cm is radiotherapy. A pre-radiation laparoscopy to investigate lymph node involvement at the lumbo-aortic level may help to define the extent of the radiation field. For endometrial cancer, the role and benefit of lymphadenectomy are much less clear since these patients often have major co-morbidities which increase the risk of complications from an extended lymph node dissection.