Genetic analysis of environmental strains of the plant pathogen Phytophthora capsici reveals heterogeneous repertoire of effectors and possible effector evolution via genomic island.
Phytophthora capsici is a virulent oomycete pathogen of many vegetable crops. Recently, it has been demonstrated that the recognition of the RXLR effector AVR3a1 of P. capsici (PcAVR3a1) triggers a hypersensitive response and plays a critical role in mediating non-host resistance. Here, we analyzed the occurrence of PcAVR3a1 in 57 isolates of P. capsici derived from globe squash, eggplant, tomato and bell pepper cocultivated in a small geographical area. The occurrence of PcAVR3a1 in environmental strains of P. capsici was confirmed by PCR in only 21 of these pathogen isolates. To understand the presence-absence pattern of PcAVR3a1 in environmental strains, the flanking region of this gene was sequenced. PcAVR3a1 was found within a genetic element that we named PcAVR3a1-GI (PcAVR3a1 genomic island). PcAVR3a1-GI was flanked by a 22-bp direct repeat, which is related to its site-specific recombination site. In addition to the PcAVR3a1 gene, PcAVR3a1-GI also encoded a phage integrase probably associated with the excision and integration of this mobile element. Exposure to plant induced the presence of an episomal circular intermediate of PcAVR3a1-GI, indicating that this mobile element is functional. Collectively, these findings provide evidence of PcAVR3a1 evolution via mobile elements in environmental strains of Phytophthora.


[A study of chronic hepatitis B infection superinfected with hepatitis E infection].
To compare the influence of hepatitis E virus (HEV) infection on the replication of hepatitis B virus (HBV) by observing clinical features, the relationship between the number of HBV DNA copies in serum, the degree of hepatic function impairments and prognosis of chronic hepatitis B patients with hepatitis E superinfection. One hundred and fifteen chronic hepatitis B (CHB) patients and 115 CHB patients with hepatitis E (HE) superinfection were studied and compared. 74 liver tissue biopsy samples of the CHB and 51 of the CHB-HE sufferers were obtained. HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HBc-IgG, anti-HBc-IgM, HBV DNA and anti-HEVIgM were detected respectively by enzyme linked immunosorbent assay and polymerase chain reaction. The number of HBV DNA copies in sera in the CHB-HE group and the severity of the clinical features were significantly higher than those in the CHB group. The former group had a poorer prognosis with a 49.6% occurrence rate of severe hepatitis and a 25.2% death rate while in the latter group the corresponding rates were just 4.4% and 1.7%. Re-infection with HEV, in those CHB patients, severely damaged their hepatic functions and increased their mortality; the older the patient and the higher the level of HBV DNA, the poorer the prognosis.


Stability of Gradient Field Corrections for Quantitative Diffusion MRI.
In magnetic resonance diffusion imaging, gradient nonlinearity causes significant bias in the estimation of quantitative diffusion parameters such as diffusivity, anisotropy, and diffusion direction in areas away from the magnet isocenter. This bias can be substantially reduced if the scanner- and coil-specific gradient field nonlinearities are known. Using a set of field map calibration scans on a large (29 cm diameter) phantom combined with a solid harmonic approximation of the gradient fields, we predicted the obtained b-values and applied gradient directions throughout a typical field of view for brain imaging for a typical 32-direction diffusion imaging sequence. We measured the stability of these predictions over time. At 80 mm from scanner isocenter, predicted b-value was 1-6% different than intended due to gradient nonlinearity, and predicted gradient directions were in error by up to 1 degree. Over the course of one month the change in these quantities due to calibration-related factors such as scanner drift and variation in phantom placement was <0.5% for b-values, and <0.5 degrees for angular deviation. The proposed calibration procedure allows the estimation of gradient nonlinearity to correct b-values and gradient directions ahead of advanced diffusion image processing for high angular resolution data, and requires only a five-minute phantom scan that can be included in a weekly or monthly quality assurance protocol.


An Aggregate Measure of Sleep Health Is Associated With Prevalent and Incident Clinically Significant Depression Symptoms Among Community-Dwelling Older Women.
Sleep can be characterized along multiple dimensions. We investigated whether an aggregate measure of sleep health was associated with prevalent and incident clinically significant depression symptoms in a cohort of older women. Participants were older women (mean age 80.1 years) who completed baseline (n = 6485) and follow-up (n = 3806) visits, approximately 6 years apart, in the Study of Osteoporotic Fractures (SOF). Self-reported sleep over the past 12 months was categorized as "good" or "poor" across 5 dimensions: satisfaction with sleep duration, daytime sleepiness, mid-sleep time, sleep onset latency, and sleep duration. An aggregate measure of sleep health was calculated by summing the number of "poor" dimensions. Clinically significant depression symptoms were defined as a score ≥6 on the Geriatric Depression Scale. Relationships between sleep health and depression symptoms were evaluated with multivariate logistic regression, adjusting for health measures and medications. Individual sleep health dimensions of sleep satisfaction, daytime sleepiness, mid-sleep time, and sleep onset latency were significantly associated with prevalent depression symptoms (odds ratios [OR] = 1.26-2.69). Sleep satisfaction, daytime sleepiness, and sleep onset latency were significantly associated with incident depression symptoms (OR = 1.32-1.79). The number of "poor" sleep health dimensions was associated in a gradient fashion with greater odds of prevalent (OR = 1.62-5.41) and incident (OR = 1.47-3.15) depression symptoms. An aggregate, multidimensional measure of sleep health was associated with both prevalent and incident clinically-significant depression symptoms in a gradient fashion. Future studies are warranted to extend these findings in different populations and with different health outcomes.


Cations as switches of amyloid-mediated membrane disruption mechanisms: calcium and IAPP.
Disruption of the integrity of the plasma membrane by amyloidogenic proteins is linked to the pathogenesis of a number of common age-related diseases. Although accumulating evidence suggests that adverse environmental stressors such as unbalanced levels of metal ions may trigger amyloid-mediated membrane damage, many features of the molecular mechanisms underlying these events are unknown. Using human islet amyloid polypeptide (hIAPP, aka amylin), an amyloidogenic peptide associated with β-cell death in type 2 diabetes, we demonstrate that the presence of Ca(2+) ions inhibits membrane damage occurring immediately after the interaction of freshly dissolved hIAPP with the membrane, but significantly enhances fiber-dependent membrane disruption. In particular, dye leakage, quartz crystal microbalance, atomic force microscopy, and NMR experiments show that Ca(2+) ions promote a shallow membrane insertion of hIAPP, which leads to the removal of lipids from the bilayer through a detergent-like mechanism triggered by fiber growth. Because both types of membrane-damage mechanisms are common to amyloid toxicity by most amyloidogenic proteins, it is likely that unregulated ion homeostasis, amyloid aggregation, and membrane disruption are all parts of a self-perpetuating cycle that fuels amyloid cytotoxicity.


Insights into the unexpected chemoselectivity in Brønsted acid catalyzed cyclization of isatins with enaminones: convenient synthesis of pyrrolo[3,4-c]quinolin-1-ones and spirooxindoles.
Divergent cascade syntheses constitute a highly attractive and challenging area in synthetic chemistry, and can exhibit unexpected chemoselectivity. Herein, a Brønsted acid-controlled protocol is described for the efficient catalysis of two different reactions, namely acylation cascade- and [1+2+3]-type cyclization of enaminones and isatins for the concise synthesis of highly functionalized pyrrolo[3,4-c]quinolin-1-ones and spirooxindoles in the presence of carboxylic acids and KHSO4, respectively. The observed chemoselectivity was reasonably explained by trapping the intermediate α,β-unsaturated 2-oxindoles, and the source of the hydroxyl group, carbocation intermediate, and amination reaction were also evaluated.


Assessing future heat stress across China: combined effects of heat and relative humidity on mortality.
This study utilizes China's records of non-accidental mortality along with twenty-five simulations from the NASA Earth Exchange Global Daily Downscaled Projections to evaluate forthcoming heat stress and heat-related mortality across China across four distinct scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The findings demonstrate a projected escalation in the heat stress index (HSI) throughout China from 2031 to 2100. The most substantial increments compared to the baseline (1995-2014) are observed under SSP5-8.5, indicating a rise of 7.96°C by the year 2100, while under SSP1-2.6, the increase is relatively modest at 1.54°C. Disparities in HSI growth are evident among different subregions, with South China encountering the most significant elevation, whereas Northwest China exhibits the lowest increment. Projected future temperatures align closely with HSI patterns, while relative humidity is anticipated to decrease across the majority of areas. The study's projections indicate that China's heat-related mortality is poised to surpass present levels over the forthcoming decades, spanning a range from 215% to 380% from 2031 to 2100. Notably, higher emission scenarios correspond to heightened heat-related mortality. Additionally, the investigation delves into the respective contributions of humidity and temperature to shifts in heat-related mortality. At present, humidity exerts a greater impact on fluctuations in heat-related mortality within China and its subregions. However, with the projected increase in emissions and global warming, temperature is expected to assume a dominant role in shaping these outcomes. In summary, this study underscores the anticipated escalation of heat stress and heat-related mortality across China in the future. It highlights the imperative of emission reduction as a means to mitigate these risks and underscores the variances in susceptibility to heat stress across different regions.


The use of artificial intelligence in interventional cardiology.
Artificial intelligence can be employed in many cardiological applications including image analysis, risk assessment, and patient monitoring. In the catheterization laboratory, it can act as a physician assistant, technician, or co-worker. First, by giving voice commands to the operator of the coronary angiography machine, it can ensure that the C-arm moves to the desired angle. It is able to make recommendations for stent size and type based on the analysis of angiography images which is also possible for peripheral and carotid interventions. For transcatheter aortic valve implantation, it can make recommendations for valve placement and size. Artificial intelligence-based image analysis algorithms can be used to support image analysis during catheter laboratory procedures. The challenges include the need for large, high-quality data sets and the development of accurate, reliable, and interpretable artificial intelligence algorithms.


A preliminary note: campus subgroup membership and football game day attire.
Differences were found in college women's attire at football games by organizational identification, perceived organizational prestige, game day attendance, and fashion opinion leadership. Factors of clothing choice were Fashion Consciousness, Desire for Comfort, Desire for Uniqueness, and Expression of School Spirit.


Sensitive detection of peptide-minicircle DNA interactions by surface plasmon resonance.
Minicircle DNA (mcDNA) is recently becoming an exciting source of genetic material for therapeutic purposes due to its exceptional biocompatibility and efficiency over typical DNA. However, its widespread use is yet restrained because of the absence of an efficient technology that allows its purification. Here, the precise conditions of mcDNA interaction with novel arginine-arginine dipeptide ligands were explored to promote binding and recovery of these biopharmaceuticals. Such interactions were investigated by taking advantage of a highly sensitive method based on surface plasmon resonance (SPR) to screen, in real-time, for ligand-coupled biomolecules, while preserving mcDNA integrity. Through this analytic approach, we detected dynamic binding responses that are dependent on buffer type, mcDNA electrokinetic potential, and temperature conditions. Remarkably, the results obtained revealed that the ligands possess high affinity to mcDNA molecules under low salt buffers, and low affinity in the presence of salt, suggesting that electrostatic interactions mainly govern ligand-analyte coupling. These findings provide important insights for an active manipulation of parameters that promote mcDNA recovery and purification. Above all, this study showed the crucial importance of SPR for future screening of other ligands that, like the one described herein, can be used to design mcDNA recovery platforms which will have significant impact in biopharmaceutical-based therapeutics.


Phosphorylation of S344 in the calmodulin-binding domain negatively affects CCaMK function during bacterial and fungal symbioses.
Calcium and Ca(2+)/calmodulin-dependent protein kinase (CCaMK) plays a critical role in the signaling pathway that establishes root nodule symbiosis and arbuscular mycorrhizal symbiosis. Calcium-dependent autophosphorylation is central to the regulation of CCaMK, and this has been shown to promote calmodulin binding. Here, we report a regulatory mechanism of Medicago truncatula CCaMK (MtCCaMK) through autophosphorylation of S344 in the calmodulin-binding/autoinhibitory domain. The phospho-ablative mutation S344A did not have significant effect on its kinase activities, and supports root nodule symbiosis and arbuscular mycorrhizal symbiosis, indicating that phosphorylation at this position is not required for establishment of symbioses. The phospho-mimic mutation S344D show drastically reduced calmodulin-stimulated substrate phosphorylation, and this coincides with a compromised interaction with calmodulin and its interacting partner, IPD3. Functional complementation tests revealed that the S344D mutation blocked root nodule symbiosis and reduced the mycorrhizal association. Furthermore, S344D was shown to suppress the spontaneous nodulation associated with a gain-of-function mutant of MtCCaMK (T271A), revealing that phosphorylation at S344 of MtCCaMK is adequate for shutting down its activity, and is epistatic over previously identified T271 autophosphorylation. These results reveal a mechanism that enables CCaMK to 'turn off' its function through autophosphorylation.


Influenza A virus PB1-F2 protein expression is regulated in a strain-specific manner by sequences located downstream of the PB1-F2 initiation codon.
Translation of influenza A virus PB1-F2 occurs in a second open reading frame (ORF) of the PB1 gene segment. PB1-F2 has been implicated in regulation of polymerase activity, immunopathology, susceptibility to secondary bacterial infection, and induction of apoptosis. Experimental evidence of PB1-F2 molecular function during infection has been collected primarily from human and avian viral isolates. As the 2009 H1N1 (H1N1pdm09) strain highlighted, some swine-derived influenza viruses have the capacity to infect human hosts and emerge as a pandemic. Understanding the impact that virulence factors from swine isolates have on both human and swine health could aid in early identification of viruses with pandemic potential. Studies examining PB1-F2 from swine isolates have focused primarily on H1N1pdm09, which does not encode PB1-F2 but was engineered to carry a full-length PB1-F2 ORF to assess the impact on viral replication and pathogenicity. However, experimental evidence of PB1-F2 protein expression from swine lineage viruses has not been demonstrated. Here, we reveal that during infection, PB1-F2 expression levels are substantially different in swine and human influenza viruses. We provide evidence that PB1-F2 expression is regulated at the translational level, with very low levels of PB1-F2 expression from swine lineage viruses relative to a human isolate PB1-F2. Translational regulation of PB1-F2 expression was partially mapped to two independent regions within the PB1 mRNA, located downstream of the PB1-F2 start site. Our data suggest that carrying a full-length PB1-F2 ORF may not be predictive of PB1-F2 expression in infected cells for all influenza A viruses.


STEMI patients receiving percutaneous coronary intervention for a culprit lesion with coronary artery bifurcation-efficacy and safety of the jailed semi-inflated balloon.
We aimed to evaluate the efficacy and safety of the 'jailed semi-inflated balloon technique' (JSIBT) for side branch (SB) protection in STEMI patients with a culprit lesion involving a coronary artery bifurcation while undergoing emergent percutaneous coronary intervention (PCI). We treated between Jan, 2011 and Jun, 2020, a total of 264 STEMI patients with a culprit lesion that involved a coronary artery bifurcation using primary PCI. In 30 patients, SB was protected by JSIBT (the JSIBT group). In 234 patients, SB was either protected or not protected by a placed wire (the non-JSIBT group). In both groups, after PCI procedure, TIMI flows of main vessel (MV) and SB were increased significantly compared with their measurements before the procedure. TIMI flows of post-procedural MV were similar between the two groups. In the JSIBT group, TIMI flows of SB both peri-procedure and post-procedure measurements were significantly greater than the non-JSIBT group. Despite a higher incidence of SB dissection in the JSIBT group, no inter-group difference was found in their total SB complications (like SB dissection, SB occlusion, wire entrapment or balloon rupture/entrapment). While JSIBT was an independent predictor for the SB TIMI 3 flow measured at the end of primary PCI, it was not an independent predictor for SB complications. The use of JSIBT as a method of SB protection during primary PCI not only provided better SB protection, but it also had a similar rate of SB complications compared with those with or without prior application of SB wire. This technique may be an effective method of protecting SB for STEMI patients involving coronary artery bifurcation and underwent emergent PCI.


Defective motor behavior and neural gene expression in RIIbeta-protein kinase A mutant mice.
Motor behavior is modulated by dopamine-responsive neurons in the striatum, where dopaminergic signaling uses G-protein-coupled pathways, including those that result in the activation of cAMP-dependent protein kinase (PKA). The RIIbeta isoform of PKA is highly enriched in the striatum, and targeted disruption of the RIIbeta gene in mice leads to a dramatic reduction in total PKA activity in this region. Although the mutant mice show typical locomotor responses after acute administration of dopaminergic drugs, they display abnormalities in two experience-dependent locomotor behaviors: training on the rotarod task and locomotor sensitization to amphetamine. In addition, amphetamine induction of fos is absent, and the basal expression of dynorphin mRNA is reduced in the striatum. These results demonstrate that motor learning and the regulation of neuronal gene expression require RIIbeta PKA, whereas the acute locomotor effects of dopaminergic drugs are relatively unaffected by this PKA deficiency.


Aversive responses by shore crabs to acetic acid but not to capsaicin.
Nociception is the ability to encode and perceive harmful stimuli and allows for a rapid reflexive withdrawal. In some species, nociception might be accompanied by a pain experience, which is a negative feeling that allows for longer-term changes in behaviour. Different types of stimuli may affect nociceptors, but in crustaceans there is conflicting evidence about the ability to respond to chemical stimuli. This study attempts to resolve this situation by testing behavioural responses of the common shore crab, Carcinus maenas, to two chemical irritants frequently used in vertebrate pain studies (acetic acid and capsaicin). In our first experiment acetic acid, water, capsaicin or mineral oil were applied by brush to the mouth, and in a second experiment treatments were applied to the eyes. Application of acetic acid had a marked effect on behaviour that included vigorous movement of mouth parts, scratching at the mouth with the claws and attempts to escape from the enclosure. Acetic acid also caused holding down of the acid-treated eye in the socket. By contrast, capsaicin had no effect and was no different to the control treatment of mineral oil and water. These results demonstrate responsiveness to acetic acid and thus nociceptive capacity for at least some chemicals. Further, the responses that persist after application were consistent with the idea of pain, however, proof of pain is not possible in any animal.


Fluid-structure interaction and structural simulation of high acceleration effects on surgical repaired human mitral valve biomechanics.
Mitral valve dynamics depend on force stability in the mitral leaflets, the mitral annulus, the chordae tendineae, and the papillary muscles. In chordal rupture conditions, the proper function of the valve disrupts, causing mitral regurgitation, the most prevalent valvular disease. In this study, Structural and FSI frameworks were employed to study valve dynamics in healthy, pathologic, and repaired states. Anisotropic, non-linear, hyper-elastic material properties applied to tissues of the valve while the first-order Ogden model reflected the best compatibility with the empirical data. Hemodynamic blood pressure of the cardiovascular system is applied on the leaflets as uniform loads varying by time, and exposure to high acceleration loads imposed on models. Immersed boundary method used for simulation of fluid in a cardiac cycle. In comparison between healthy and pathologic models, stress values and chordal tensions are increased, by nearly threefold and twofold, respectively. Stress concentration on leaflets is reduced by 75% after performing a successful surgical repair on the pathological model. Crash acceleration loads led to more significant stress and chordae tension on models, by 27% and 23%, respectively. It is concluded that a more sophisticated model could lead to a better understanding of human heart valve biomechanics in various conditions. If a preoperative plan is developed based on these modeling methods, the requirement for multiple successive repairs would be eliminated, operative times are shortened, and patient outcomes are improved.


The Austrian Bone Marrow Donor Registry: Providing Patients in Austria with Unrelated Donors for Transplant - a Worldwide Cooperation.
BACKGROUND: The Austrian Bone Marrow Donor Registry is the central search coordinating unit in charge of national and international donor searches in Austria. PATIENTS AND METHODS: Between 1988 and 2010, a worldwide search for an unrelated donor of blood stem cells (URD) was initiated for 2,166 Austrian patients with haematological disorders, 1,671 adults and 495 children, by the Austrian Bone Marrow Donor Registry. RESULTS: An URD was identified for 78.3% of the patients between 2008 and 2010, for 76.7% of the patients between 2004 and 2007, for 71.3% between 1996 and 2003, but only for 53.4% of the patients in the initial period of 1988-1995. Thus, results of international donor searches improve over time. In contrast, search duration decreases steadily: Search times of successful searches decreased from about 8 months in the first period between 1988 and 1996 to 1.84 months in 2010. Overall, 1,558 of the 2,166 patients (71.9%) could be provided with a matching donor. However, not every patient provided with a URD was transplanted. Overall, only 1,141 of 2,166 patients (52.7%) proceeded to transplant. CONCLUSION: Figures have significantly improved for the latest period of donor searches between 2008 and 2010. In this period, a donor could be found for 78.3%, and 58.5% of the patients received a transplant.


Determinants of Stock Theft and Its Implication on Household Dietary Diversity in Semiarid Regions of Zimbabwe: Case of Gwanda District.
Stock theft is a major threat to livestock production in Africa and has been on the rise in recent years. Zimbabwe is no exception. The purpose of this study was to analyze factors that contribute to stock theft in rural areas. The study used a mixed research design. The study was limited to wards 20 and 24 of Gwanda district of Matabeleland South Province. The linear regression model was used to analyze the factors that affected stock theft in rural areas. The majority (57.1%) of the interviewed household heads were males and aged below 50 years (55.8%) with an average household size of 5 members. On average, each household owned 5 cattle, 2 sheep, 17 goats, 4 donkeys, and 5 chicken. The participants kept livestock mainly for income generation, source of school fees, draught power, meat, milk, manure, and eggs. The major causes of livestock loss apart from stock theft were drought, disease outbreaks, trapped in mine holes, and predators. All the respondents practiced livestock identification which includes branding, ear notching, and the use of ear tags. The most vulnerable livestock species to stock theft were goats, cattle, donkeys, sheep, and chicken. Stock theft mostly takes place before midday and on Mondays and Wednesdays. It is at its peak levels in January and November. Goats and donkeys were the main stolen livestock species. The stolen livestock is mostly sold to meat processors. The distance from the border, the use of livestock identification tags, the total number of livestock units owned by the household, and the day of the week were significant in influencing the intensity of stock theft (p < 0.10). Stock theft does not directly affect household dietary diversity (p > 0.05) because rural households do not use livestock for their nutritional benefit, particularly goats, sheep, and cattle. Thus, if dietary diversity is taken as a proxy for food security, it can be concluded that stock theft does not significantly affect the household's food security status. Working in groups through neighborhood watch committees, livestock branding, tending livestock which reduces the time that the livestock roam freely unattended, and assisting the police with investigations whenever there is a case of stock theft were identified as important mitigation strategies. At the service provider level, it was suggested that the law enforcing needed to increase its efficiency to mitigate stock theft.


Homeobox gene Sax2 deficiency causes an imbalance in energy homeostasis.
The brain, in particular the hypothalamus and the brainstem, plays a critical role in the regulation of energy homeostasis by incorporating signals from the periphery and translating them into feeding behavior. Here we show that the homeobox gene Sax2, which is expressed predominantly in the brainstem, in the vicinity of serotonergic neurons, contributes to this physiological balance. Sax2 deficiency results in a decrease of fat and glycogen storage, reduced blood glucose levels, and raised serotonin levels in the hindbrain. Surprisingly, in the brainstem the expression levels of pro-opiomelanocortin and neuropeptide Y were indicative of a fasting condition, opposed to the observed high serotonin levels implying satiation. Furthermore, Sax2-directed lacZ expression reveals a dramatic change of the distribution of Sax2-expressing cells in the null mutant occurring during perinatal development. These data strongly suggest that Sax2 is required for the coordinated crosstalk of factors involved in the maintenance of energy homeostasis.


Dignified Resources and Coping Strategies During the COVID-19 Pandemic: a Qualitative Study of Racially and Economically Marginalized Communities.
Amid the spread of the novel coronavirus (COVID-19), racially and economically marginalized communities experienced a disproportionate burden of disease and social consequences (e.g., unemployment, increased exposure). This study seeks to understand strategies that these communities employed to cope with unequal burdens of the pandemic. We utilized qualitative data collected between 2020 and 2021 from a mobile mapping platform designed to facilitate real-time, geocoded data collection on individual's experiences and perceptions of their neighborhoods. Reports were iteratively coded by an academic researcher and community partner. We employed an inductive approach to analysis, which allowed findings to emerge organically without constraint of researcher hypotheses. A total of 19 respondents (14 under the age of 45, 16 non-White, 15 with less than half a year of emergency savings) provided 236 qualitative reports. Participants described innovative strategies for exchanging resources as a means of informally networking and building community, the importance of tailored programming (e.g., for specific racial/ethnic groups) in fostering belonging and comfort, and the importance of two specific dimensions of services-interactions with service providers and the quality of goods or services-in providing dignified care. Amidst exacerbated racial and economic disparities emerging from the COVID-19 pandemic, our study highlights the need for investment in mutual aid, the importance of tailored services and support, and promoting dignity in social services. As other macro-level social stressors become more prevalent as the pandemic continues, these findings can inform how we examine and address them.


Gas6'ing the innate immune response during experimental asthma.
Growth arrest-specific gene 6 (Gas6) binds Tyro3, Axl, and Mertk (TAM) receptors and exerts prominent effects in many diseases, but little is known about its role in asthma. Herein, we examined the role of Gas6 and TAM receptors differentially in an experimental asthma model driven by Aspergillus fumigatus. A. fumigatus-sensitized mice were challenged with live A. fumigatus conidia, and airway hyperresponsiveness and airway remodeling were determined 28 days later. When administered to mice from Days 14 to 28 after conidia challenge, anti-Axl monoclonal antibody, but not anti-Mertk monoclonal antibody, treatment significantly inhibited airway hyperresponsiveness and airway remodeling compared with the appropriate control IgG group. These results demonstrate that Gas6 has modulatory functions in fungal asthma via Axl receptor activation in immune and nonimmune cells.


[Current views on pathogenesis and treatment of anemia in rheumatoid arthritis].
Anemia, especially anemia of chronic disease (ACD), is a frequent manifestation of rheumatoid arthritis. In the paper the mechanisms involved in the development of ACD and other causes of anemia in this disorder are reviewed. The new aspects in the treatment of anemia associated with rheumatoid arthritis, including erythropoietin, iron and chelation therapy are also discussed.


A dual-process approach to prosocial behavior under COVID-19 uncertainty.
Uncertainty has been shown to reduce the willingness to cooperate in various social dilemmas and negatively affect prosocial behavior. However, some studies showed that uncertainty does not always decrease prosocial behavior, depending on the type of uncertainty. More specifically, recent research has shown that prosocial behavior tends to increase under impact uncertainty-uncertainty about the consequences for others if they become infected. In addition, researchers have argued that intuition favors prosocial behavior while deliberation leads to selfish behavior. Our study explored how intuitive (time pressure) or deliberate mental processing, under outcome, or impact uncertainty affect prosocial behavior in the context of the COVID-19 pandemic. Our sample consists of 496 participants, and we used a 4 (COVID-19 scenario: Control vs. Impact Uncertainty vs. Worst-Case vs. Indirect Transmission) by 2 (decision time: time delay vs. time pressure) between-subjects design. Results suggest that participants are more inclined to stay at home (prosocial intention) when forced to make their decisions intuitively rather than deliberately. Additionally, we found that uncertainty does not always decrease prosocial behavior. It seems that uncertainty does not affect the prosocial intention in a scenario with a real infectious disease. These findings suggest that the distinction between outcome and impact uncertainty may be due to the realism of experimental stimuli interventions.


Hepatotoxicity of commonly used drugs: nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, psychotropic drugs.
Hepatotoxic adverse drug reactions have contributed to the decline of many promising therapies, even among mainstream medication classes (bromfenac and troglitazone are recent examples). The spectrum of nonsteroidal anti-inflammatory drug-related liver toxicity continues to expand, with reports in children, interactive toxicity in persons with hepatitis C, and recognition of the toxicity of both the preferential and selective cyclooxygenase-2 inhibitors. Of the antihypertensive agents, methyldopa is now rarely prescribed and adverse effects are reported infrequently, whereas cases of liver injury associated with the angiotensin receptor and converting enzyme inhibitors are increasingly reported. Of the antidiabetic agents, acarbose, gliclazide, metformin, and human insulin have been implicated in causing liver injury. To date, the newer thiazolidinediones do not appear to share the hepatotoxic potential of troglitazone, although a few reports of acute hepatitis have accrued. Although liver injury has been associated with the "statins," the frequency of such toxicity is lower than that of the background population and the value of biochemical monitoring remains unproved. Newer concepts in anticonvulsant hepatotoxicity have been the recognition of the reactive metabolite syndrome, delineation of the risk factors for valproic acid toxicity, the potential role of carnitine in preventing valproic acid hepatotoxicity, and the toxicity of second-line antiepileptic drugs. Liver injury associated with newer psychotropic agents, particularly the selective serotonin reuptake inhibitors, is also discussed. The focus of the review is the hepatotoxicity of commonly used drugs with particular reference to recent and novel reports of toxicity. Well-known causes of liver injury such as chlorpromazine, phenytoin, and methyldopa are not discussed.


Clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma.
More knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies. We investigated the clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma. One hundred ninety-four patients with curatively resected intrahepatic cholangiocarcinoma were included in this study. Tumor tissue specimens were collected and analyzed for ROS1 gene rearrangement using fluorescence in situ hybridization (FISH) and ROS1 protein expression using immunohistochemistry (IHC). ROS1 immunohistochemistry was positive (moderate or strong staining) in 72 tumors (37.1 %). ROS1 protein expression was significantly correlated with well differentiated tumors, papillary or mucinous histology, oncocytic/hepatoid or intestinal type tumors, and periductal infiltrating or intraductal growing tumors (vs. mass-forming cholangiocarcinoma). ROS-expressing tumors were associated with better disease-free survival (30.1 months for ROS1 expression (+) tumors vs. 9.0 months for ROS1 (-) tumors, p = 0.006). Moreover, ROS1 expression was an independent predictor of better disease-free survival in a multivariate analysis (HR 0.607, 95 % CI 0.377-0.976; p = 0.039). Although break-apart FISH was successfully performed in 102 samples, a split pattern indicative of ROS1 gene rearrangement was not found in the examined samples. ROS1 protein expression was associated with well-differentiated histology and better survival in our patients with resected intrahepatic cholangiocarcinoma. ROS1 gene rearrangement by break-apart FISH was not found in the examined samples.


Autobiographical memories of vomiting in people with a specific phobia of vomiting (emetophobia).
Vomiting is an almost universal phenomenon, but little is known about the aetiology of a specific phobia of vomiting (SPOV). The associations with vomiting during childhood and autobiographical memories may have relevance for our understanding of the development of SPOV and its treatment. Two groups: (a) a group with SPOV (n = 94) and (b) a control group (n = 90) completed a self-report questionnaire assessing their lifetime memories of both their own vomiting and others vomiting. People with SPOV recalled the memories of their own and others vomiting experiences from an earlier age and rated them as significantly more distressing than the control group. There was no difference between the groups in the number of memories of their own vomiting recalled before the age at which vomiting became a problem. However, the SPOV group recalled more memories of others vomiting before the onset of the problem. After the age at which the phobia became a problem they recalled less memories of their own vomiting and more memories of others vomiting than the control group. They recalled significantly more memories of vomiting associated with inter-personal events, health or emotional or unrelated life events. Avoidance and hyper-vigilance for others vomiting after the onset of the phobia may have slightly reduced the risk of vomiting. There is some evidence for associative learning in SPOV with aversive consequences of vomiting and an unrelated life event. It suggests a model of autobiographical memories of vomiting that have lost a time perspective and context, which are being reactivated with cues for vomiting. The limitations of the study are those of memory biases in both groups.


Approaches to imaging unfolded secretory protein stress in living cells.
The endoplasmic reticulum (ER) is the point of entry of proteins into the secretory pathway. Nascent peptides interact with the ER quality control machinery that ensures correct folding of the nascent proteins. Failure to properly fold proteins can lead to loss of protein function and cytotoxic aggregation of misfolded proteins that can lead to cell death. To cope with increases in the ER unfolded secretory protein burden, cells have evolved the Unfolded Protein Response (UPR). The UPR is the primary signaling pathway that monitors the state of the ER folding environment. When the unfolded protein burden overwhelms the capacity of the ER quality control machinery, a state termed ER stress, sensor proteins detect accumulation of misfolded peptides and trigger the UPR transcriptional response. The UPR, which is conserved from yeast to mammals, consists of an ensemble of complex signaling pathways that aims at adapting the ER to the new misfolded protein load. To determine how different factors impact the ER folding environment, various tools and assays have been developed. In this review, we discuss recent advances in live cell imaging reporters and model systems that enable researchers to monitor changes in the unfolded secretory protein burden and activation of the UPR and its associated signaling pathways.


The Serengeti food web: empirical quantification and analysis of topological changes under increasing human impact.
1. To address effects of land use and human overexploitation on wildlife populations, it is essential to better understand how human activities have changed species composition, diversity and functioning. Theoretical studies modelled how network properties change under human-induced, non-random species loss. However, we lack data on realistic species-loss sequences in threatened, real-world food webs to parameterize these models. 2. Here, we present a first size-structured topological food web of one of the most pristine terrestrial ecosystems in the world, the Serengeti ecosystem (Tanzania). The food web consists of 95 grouped nodes and includes both invertebrates and vertebrates ranging from body masses between 10(-7) and 10(4) kg. 3. We study the topological changes in this food web that result from the simulated IUCN-based species-loss sequence representing current species vulnerability to human disturbances in and around this savanna ecosystem. We then compare this realistic extinction scenario with other extinction sequences based on body size and connectance and perform an analysis of robustness of this savanna food web. 4. We demonstrate that real-world species loss in this case starts with the biggest (mega) herbivores and top predators, causing higher predator-prey mass ratios. However, unlike theoretically modelled linear species deletion sequences, this causes poor-connected species to be lost first, while more highly connected species become lost as human impact progresses. This food web shows high robustness to decreasing body size and increasing connectance deletion sequences compared with a high sensitivity to the decreasing connectance deletion scenario. 5. Furthermore, based on the current knowledge of the Serengeti ecosystem, we discuss how the focus on food web topology alone, disregarding nontrophic interactions, may lead to an underestimation of human impacts on wildlife communities, with the number of trophic links affected by a factor of two. 6. This study underlines the importance of integrative efforts between the development of food web theory and basic field work approaches in the quantification of the structure of interaction networks to sustain natural ecosystems in a changing world.


A versatile and reconfigurable setup for all-terahertz time-resolved pump-probe spectroscopy.
A versatile optical setup for all-terahertz (THz) time resolved pump-probe spectroscopy was designed and tested. By utilizing a dual THz pulse generator emitter module, independent and synchronized THz radiation pump and probe pulses were produced, thus eliminating the need for THz beam splitters and the limitations associated with their implementation. The current THz setup allows for precise control of the electric fields splitting ratio between the THz radiation pump and probe pulses, as well as in-phase, out-of-phase, and polarization dependent pump-probe spectroscopy. Since the present THz pump-probe setup does not require specialized THz radiation optical components, such as phase shifters, polarization rotators, or wide bandwidth beam splitters, it can be easily implemented with minimal alterations to a conventional THz time domain spectroscopy system. The present setup is valuable for studying the time dynamics of THz coherent phenomena in solid-state, chemical, and biological systems.


[Short-course kidney-invigorating therapy improves near-term semen quality in asthenozoospermic men with kidney deficiency].
To evaluate the effect of short-course kidney-invigorating therapy on near-term semen quality in asthenozoospermic men with kidney deficiency. Based on the differential types in traditional Chinese medicine, 121 asthenozoospermia patients received at our clinic of andrology were divided into groups A (kidney-yin deficiency), B (kidney-yang deficiency) and C (spleen and kidney deficiency), and treated with Yougui Decoction plus Wuziyanzong Pills, Jinkuishenqi Pills plus Wuziyanzong Pills, and Shizi Decoction plus Liujunzi Decoction, respectively, all given once daily for 4 weeks. Sperm parameters of the patients were analyzed with the computer-assisted sperm analysis system before and after treatment and compared among the three groups. The baseline sperm concentrations in groups A, B and C ([70.4 +/- 38.6], [73.5 +/- 40.2] and [56.0 +/-34.4] x 10(6)/ml) showed no significant differences from those after medication ([74.4 +/- 32.6], [67.0 +/- 30.8] and [58.6 +/- 24.6] x 10(6)/ml) (P > 0.05). The percentages of grade a sperm in the three groups were (12.9 +/- 5.3)%, (13.7 +/- 7.7)% and (12.9 +/- 6.4)% respectively after treatment, significantly higher than (9.9 +/- 6.7)%, (9.3 +/- 5.4)% and (9.0 +/- 6.8)% before treatment (P < 0.05), and so were the percentages of grade a + b sperm ([37.4 +/- 10.2 ]%, [35.7 +/- 13.7]% and [35.9 +/- 12.3]% after treatment versus [29.6 +/- 13.2]%, [27.5 +/- 10.4]% and [28.3 +/- 12.1]% before treatment, P < 0.05). All the three groups showed significantly increased sperm motility after treatment ([53.8 +/- 10.5]%, [52.6 +/- 15.2]% and [51.1 +/- 13.1]%) as compared with the baseline levels ([44.3 +/- 14.0]%, [43.5 +/- 15.0]% and [42.4 +/- 14.9]%) (P < 0.05). The cure rate and total effectiveness rate were significantly higher in group B than in A (P < 0.05), but had no significant differences between either A and C or B and C (P > 0.05). Short-course kidney-invigorating therapy can significantly improve near-term semen quality in asthenozoospermic men with kidney asthenia, especially in those with kidney-yang deficiency, and it has no obvious adverse effects.


Effect of chlorogenic acid on intestinal inflammation, antioxidant status, and microbial community of young hens challenged with acute heat stress.
Heat stress in poultry is deleterious to productive performance. Chlorogenic acid (CGA) exerts antibacterial, anti-inflammatory, and antioxidant properties. This study was conducted to evaluate the effects of dietary supplemental CGA on the intestinal health and cecal microbiota composition of young hens challenged with acute heat stress. 100-day-old Hy-line brown pullets were randomly divided into four groups. The control group (C) and heat stress group (HS) received a basal diet. HS + CGA300 group and HS + CGA600 group received a basal diet supplemented with 300- and 600-mg/kg CGA, respectively, for 2 weeks before heat stress exposure. Pullets of HS, HS + CGA300 , and HS + CGA600 group were exposed to 38°C for 4 h while the control group was maintained at 25°C. In this study, dietary CGA supplementation had effect on mitigate the decreased T-AOC and T-SOD activities and the increasing of IL-1β and TNFα induced by acute heat stress. Dietary supplementation with 600 mg/kg CGA had better effect on increasing the relative abundance of beneficial bacterial genera, such as Rikenellaceae RC9_gut_group, Ruminococcaceae UCG-005, and Christensenellaceae R-7_group, and deceasing bacteria genera involved in inflammation, such as Sutterella species. Therefore, CGA can ameliorate acute heat stress damage through suppressing inflammation and improved antioxidant capacity and cecal microbiota composition.


[Mechanical properties and biocompatibility of nanometer calcium carbonate/poly (L-lactide) composites].
The purpose of this study is to synthesize nanometer calcium carbonate/poly(L-lactide) composites and evaluate its biocompatibility, and mechanical properties. The nanometer calcium carbonate/poly(L-lactide) composites was prepared by the method of solution mixing and cell culture. Its properties were analyzed using, mechanical tests, MTT assay, transmission electron microscope and scanning electron microscope. It was found that the new kind copolymer had good biocompatibility, nanometer calcium carbonate could enhance the strength of the pure poly (L-lactide) matrix. The nanometer calcium carbonate/poly (L-lactide) composites is a promising bioabsorbable material. It is worth further medical research.


Influence of grilling pretreatment and optimization of sous vide processing parameters on the physicochemical and microbiological quality of pirarucu fillet.
The demand for high-quality food products has promoted the study of techniques for its processing and conservation. The present research aimed to evaluate the influence of grilling pretreatment on the physical characteristics of pirarucu fillets and the heat transfer process by a computational modelling, and to optimize the sous vide process parameters. Before and after the sous vide process, the samples were analysed for microbiological, chemical and physical characteristics. There was no significant difference between the total experimental time of grilling and that obtained by computational modelling. Immersion in brine for 300 s in combination with grilling at 200 ℃/120 s was selected because of its water-holding capacity (%) 79.40 ± 0.31, texture (N) 1.91 ± 0.40 and value of L* 74.44 ± 0.38 in the fillets. Cooking at 60 ℃ for 568.8 s were the best sous vide parameters obtained, with highest water-holding capacity (%) 93.60, texture (N) 6.24, ΔE* 7.43, and with microbiological loads below 6 log CFU/g and 7 log MPN/g in the final product. Useful information obtained from this study highlighted the brine and grill pretreatment in combination with sous vide proved it is a potential solution for developing pirarucu products even at an industrial scale.


Serum starvation induces sexual dimorphisms in secreted proteins of human umbilical vein endothelial cells (HUVECs) from twin pairs.
There is growing evidence for sex and gender differences in the clinical manifestation and outcomes of human diseases. Human primary endothelial cells represent a useful cardiovascular model to study sexual dimorphisms at the cellular level. Here, we analyzed sexual dimorphisms of the secretome after serum starvation using human umbilical vein endothelial cells (HUVECs) from twin pairs of the opposite sex to minimize the impact of varying genetic background. HUVECs were starved for 5 and 16 h, respectively, and proteins of the cell culture supernatants were analyzed by tandem mass spectrometry. Altogether, 960 extracellular proteins were identified of which 683 were amendable to stringent quantification. Significant alterations were observed for 455 proteins between long-term and short-term starvation and the majority were similar in both sexes. Only 5 proteins showed significant sex-specific regulation between long-versus short-term starvation. Furthermore, 19 unique proteins with significant sexual dimorphisms at the same time points of serum starvation were observed. A larger number of proteins, for example tissue factor inhibitor 2 (TFPI2), displayed higher levels in the supernatants of females compared to male cells after long term serum starvation that might point to higher adaptation capacity of female cells. The overall results demonstrate that male and female cells differ in their secretome.


Targeting BET bromodomain proteins in solid tumors.
There is increasing interest in inhibitors targeting BET (bromodomain and extra-terminal) proteins because of the association between this family of proteins and cancer progression. BET inhibitors were initially shown to have efficacy in hematologic malignancies; however, a number of studies have now shown that BET inhibitors can also block progression of non-hematologic malignancies. In this Review, we summarize the efficacy of BET inhibitors in select solid tumors; evaluate the role of BET proteins in mediating resistance to current targeted therapies; and consider potential toxicities of BET inhibitors. We also evaluate recently characterized mechanisms of resistance to BET inhibitors; summarize ongoing clinical trials with these inhibitors; and discuss potential future roles of BET inhibitors in patients with solid tumors.


Epigenetic Guardian: A Review of the DNA Methyltransferase DNMT3A in Acute Myeloid Leukaemia and Clonal Haematopoiesis.
Acute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon. These mutations have been associated with poor prognosis and adverse survival outcomes for AML patients. Advances in whole-exome sequencing techniques have recently identified a large number of DNMT3A mutations present in clonal cells in normal elderly individuals with no features of haematological malignancy. Categorically distinct from other preleukaemic conditions, this disorder has been termed clonal haematopoiesis of indeterminate potential (CHIP). Further insight into the mutational landscape of CHIP may illustrate the consequence of particular mutations found in DNMT3A and identify specific "founder" mutations responsible for clonal expansion that may contribute to leukaemogenesis. This review will focus on current research and understanding of DNMT3A mutations in both AML and CHIP.


Myxoid change in nondecidualized cutaneous endometriosis resembling malignancy.
Cutaneous endometriosis infrequently arises in the absence of pelvic disease. Rare features such as myxoid change can resemble malignancy and may pose a challenging histological diagnosis. We are not aware of any previous cases involving nondecidualized cutaneous endometriosis with myxoid change associated with an abdominal surgical scar. We report the first such case in which a 24-year-old woman presented with a steadily growing, firm, tender, painful, subcutaneous cicatrical mass that had appeared shortly after cesarean section 1 year previously. The mass was removed and permanent sections revealed foci of large, irregular endometrial glands embedded within prominent myxoid stroma and acellular mucin pools, with fibrosis and pseudoinfiltration of the fascia. No evidence of malignancy was identified. This case demonstrates that nondecidualized cutaneous endometriosis with myxoid change should be considered in the differential diagnosis of histologically similar malignancies such as mucinous adenocarcinoma and pseudomyxoma peritonei.


Neonatal Pain And Preventive Strategies: An Experience In A Tertiary Care Unit.
Little is known about neonatal pain in Pakistan. So, to know about neonatal pain, its scoring and the effectiveness of oral dextrose in neonatal pain management we carried this study in neonatal intensive care unit (NICU) of military hospital (MH) Rawalpindi. This randomized control trial was carried out in NICU of MH, Rawalpindi from Jan to Dec 2013. Total of 252 babies were enrolled in the study. We assessed neonatal pain by using Modified Behavioural Pain Scale (MBPS). Babies were given 10% dextrose and sterile water two minutes before a painful procedure and pain assessment was done after the procedure. The different painful procedures included, heel prick, nasogastric (NG) tube insertion, cannulation, catheterization and venepuncture for blood sampling. A total of 252 babies were enrolled in the study. Of these 139 (55%) were male and 113 (45%) were female babies. Painful procedures included heel lancing 120 (48%), I/V cannulations 60 (24%), venepuncture 40 (16%), NG insertion 26 (10%) and Foley catheterization 6 (2%). Mean MBPS score with 10% dextrose and sterile water were 4.31 and 6.26 respectively and the difference between two was significant statically. Oral dextrose is a cheap and easily available solution and can be used in neonatal pain management during various painful procedures.


HIV-Associated Cryptococcal Disease in Resource-Limited Settings: A Case for "Prevention Is Better Than Cure"?
Cryptococcal disease remains a significant source of global morbidity and mortality for people living with HIV, especially in resource-limited settings. The recently updated estimate of cryptococcal disease revealed a global incidence of 223,100 cases annually with 73% of these cases being diagnosed in sub-Saharan Africa. Furthermore, 75% of the estimated 181,100 deaths associated with cryptococcal disease occur in sub-Saharan Africa. Point-of-care diagnostic assays have revolutionised the diagnosis of this deadly opportunistic infection. The theory of asymptomatic cryptococcal antigenaemia as a forerunner to symptomatic meningitis and death has been conclusively proven. Thus, cryptococcal antigenaemia screening coupled with pre-emptive antifungal therapy has been demonstrated as a cost-effective strategy with survival benefits and has been incorporated into HIV national guidelines in several countries. However, this is yet to be implemented in a number of other high HIV burden countries. Flucytosine-based combination therapy during the induction phase is associated with improved survival, faster cerebrospinal fluid sterilisation and fewer relapses. Flucytosine, however, is unavailable in many parts of the world. Studies are ongoing on the efficacy of shorter regimens of amphotericin B. Early diagnosis, proactive antifungal therapy with concurrent management of raised intracranial pressure creates the potential to markedly reduce mortality associated with this disease.


The fibrinogen-like domain of FREP1 protein is a broad-spectrum malaria transmission-blocking vaccine antigen.
FREP1 in mosquito midguts facilitates Plasmodium falciparum parasite transmission. The fibrinogen-like (FBG) domain of FREP1 is highly conserved (>90% identical) among Anopheles species from different continents, suggesting that anti-FBG antibodies may block malaria transmission to all anopheline mosquitoes. Using standard membrane-feeding assays, anti-FREP1 polyclonal antibodies significantly blocked transmission of Plasmodium berghei and Plasmodium vivax to Anopheles gambiae and Anopheles dirus, respectively. Furthermore, in vivo studies of mice immunized with FBG achieved >75% blocking efficacy of P. berghei to A. gambiae without triggering immunopathology. Anti-FBG serum also reduced >81% of P. falciparum infection to A. gambiae Finally, we showed that FBG interacts with Plasmodium gametocytes and ookinetes, revealing the molecular mechanism of its antibody transmission-blocking activity. Collectively, our data support that FREP1-mediated Plasmodium transmission to mosquitoes is a conserved pathway and that targeting the FBG domain of FREP1 will limit the transmission of multiple Plasmodium species to multiple Anopheles species.


Influence of Aldo-keto Reductase 1C3 in Prostate Cancer - A Mini Review.
Aldo-keto reductase 1C3 (AKR1C3) is an important oxidoreductase with multiple substrates, that are involved in producing extra-testicular androgens. Its activity is influenced by environmental exposures, as well as by genetic variants. These genetic variants could therefore produce variable testosterone levels and subsequent androgen receptor (AR) activation. This could lead to differential downstream production of the prostate-specific antigen (PSA). As PSA level is used for clinical evaluation of the prostate, these variations could impact prostate cancer (PC) diagnosis, as well as PC management outcomes. This review brings together information with regards to key functions of this enzyme, its relevance in PC, its transcriptional regulation, clinical aspects associated with genetics, differential regulation in cancer and cancer progression, and the types of AKR1C3 inhibitors with future therapeutic value. Based on these discussions, hypotheses are forwarded for future applicability of this enzyme and its genetic variants in transformational medical practices in PC. Options for the use of personalised AKR1C3 inhibitor drugs for late stage PC are also discussed.


Concanavalin A binding of alpha-fetoprotein in amniotic fluid as an aid in the diagnosis of neural tube defects.
Concanavalin A nonreactive alpha-fetoprotein was determined in samples of amniotic fluid from 16 abnormal pregnancies complicated by anencephaly (7), open spina bifida (6), intra-uterine death (1), anencephaly with exomphalos (1), or open spina bifida with exomphalos (1), and in amniotic fluid from 50 normal pregnancies with gestational age between 13 and 24 weeks. In all 16 cases with fetal malformations, the proportion of nonreactive alpha-fetoprotein was significantly decreased (median 5.3%) as compared with amniotic fluid from pregnancies with a normal outcome (median 39.7%). The results confirm that this measurement is useful in the diagnosis of neural tube defects, especially when the concentration of alpha-fetoprotein in amniotic fluid is normal or only slightly above normal and gestational age is uncertain.


Urinary transglutaminase 2 as a potent biomarker to predict interstitial fibrosis and tubular atrophy of kidney allograft during early posttransplant period in deceased donor kidney transplantation.
Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis. We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant. In addition, kidney allograft tissue specimens at 0-day and 6-month posttransplant were sampled to analyze the correlation of urinary TG2 and kidney allograft fibrosis. Thirteen recipients had increased interstitial fibrosis and tubular atrophy (IFTA) scores at the 6-month protocol biopsy (IFTA group). The mean level of urinary TG2 in the IFTA group was higher compared to that of 5 other recipients without IFTA (no IFTA group). Conversely, the mean level of urinary syndecan-4 in the IFTA group was lower than levels in patients without IFTA. In the IFTA group, double immunofluorescent staining revealed that TG2 intensity was significantly upregulated and colocalizations of TG2/heparin sulfate proteoglycan and nuclear syndecan-4 were prominent, usually around tubular structures. Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis.


The effect of tourniquet usage on cement penetration in total knee arthroplasty: A prospective randomized study of 3 methods.
It is a randomized study to compare cement penetration on x-rays after total knee arthroplasty (TKA) among 3 different ways to use tourniquets; application during the surgery, application only with implantation prosthesis and with no tourniquet use. A total 69 knees of 59 patients were included in the study in a quasirandom manner. Each patient had physical exams and standard radiographic evaluations at 6 weeks after the TKA procedure. Outcome evaluations included visual analog scale (VAS) scores, Knee Society Scores (KSS), blood transfusion, and drainage status after surgery for all groups. For radiographic review, the tibial plateau was divided into zones in the anterior-posterior and lateral views, according to the Knee Society Scoring System. The average age of the patients who were eligible for the study was 65.05 (range 46-81) years. All 59 patients included in the study were female patients. Group 1 consisted of 24 patients who had TKA with use of a tourniquet during the entire operation. Group 2 consisted of 20 patients who had TKA with use of tourniquet only at the time of cementing and group 3 consisted of 25 patients with no use tourniquet. There is no significant difference in early cement penetration among the groups (group 1 2.50 mm, group 2 2.28 mm, group 3 2.27 mm; group 1 vs 2 P = .083, group 1 vs 3 P = .091, group 2 vs 3 P = .073). There is no significant difference for postoperative drainage among the 3 groups (group 1 245 mL, group 2 258.76 mL, group 3 175.88 mL; group 1 vs 2 P = .081, group 1 vs 3 P = .072, group 2 vs 3 P = .054). There was no need to transfuse more than 1 unit in any patient. The VAS score was significantly higher (group 1 3.58, group 2 1.55, group 3 1.52; group 1 vs 2 P = .022, group 1 vs 3 P = .018, group 2 vs 3 P = .062) and KSS was significantly lower in the tourniquet group (group 1 63, group 2 79, group 3 82; group 1 vs 2 P = .017, group 1 vs 3 P = .02, group 2 vs 3 P = .082). We do not suggest long-duration tourniquet use, which can lead higher pain scores and reduce functional recovery after total knee arthroplasty.


High dietary zinc and fasting as methods of forced resting: a performance comparison.
A study was conducted to compare fasting and high dietary zinc as procedures to induce a forced rest of laying hens. Five to six replicates (25 hens each) of Single Comb White Leghorn hens laying approximately 60% were fasted for 10 days (fasted) or fed either 10,000 ppm zinc (10 Zn) or 20,000 ppm zinc (20 Zn) for a period of 4 days. A fourth treatment consisted of feeding 20,000 ppm zinc for 8 days (20 Zn-8). During the rest-inducing period, hens consumed little of either high zinc diet. Four-day intake by 20 Zn hens averaged 17.6 +/- .2 g/hen/day compared to 32.6 +/- 1.5 g/hen/day (means +/- SEM) for 10 Zn hens. Those fed 20 Zn-8 consumed the least amount, 12.6 +/- .2 g/hen/day during the 8 days of high zinc feeding. Body weight loss of hens in this last group was comparable to hens fasted for 10 days (fasted), i.e., 24.6 +/- .3% vs. 27.6 +/- .4%. Weight loss of hens in the remaining two groups reflected, to some extent, differences in feed consumption. The 20 Zn hens lost significantly more body weight during the 4-day period when compared with 10 Zn hens (16.2 +/- .4% vs. 11.9 +/- .5%). Each treatment resulted in a sharp drop in egg production. By the 5th day, fasted, 20 Zn, and 20 Zn-8 hens had ceased producing eggs. Egg production by 10 Zn hens declined at a slightly slower rate. There were considerable differences in post-rest egg production among the various treatments.(ABSTRACT TRUNCATED AT 250 WORDS)


Hexagonal pattern instabilities in rotating Rayleigh-Bénard convection of a non-Boussinesq fluid: experimental results.
Motivated by the Küppers-Lortz instability of roll patterns in the presence of rotation, we have investigated the effects of rotation on a hexagonal pattern in Rayleigh-Bénard convection. While several theoretical models have been developed, experimental data cannot be found in the literature. In order to check the validity of the predictions and to study the effects of rotation on the behavior of the system, we present experimental results for a non-Boussinesq Rayleigh-Bénard convection with rotation about the vertical axis. Rotation introduces an additional control parameter, namely the dimensionless rotation rate Omega= 2 pi f d(2)/nu, where f is the rotation rate (in Hz), d is the thickness of the cell, and nu is the kinematic viscosity. We observe that the cell rotation induces a slow rotation of the pattern in the opposite direction (approximately Omega x 10(-4) ) in the rotating frame. Moreover, it tends to destroy the convective pattern. No oscillation of the hexagonal pattern over the range of its existence (Omega< or =6) has been observed.


Child welfare services for the catastrophically ill newborn: Part I--A confusion of responsibility.
The majority of these difficult bioethical decisions should properly be made by parents with input from physician and health care workers, utilizing the resources and guidance of infant ethics committees within the involved hospitals. The child protective service system should have the final authority, however, to assure that the decisions of the "caregivers" do not constitute abuse or neglect. This will require that the child welfare system sometimes walk the razor's edge between protecting the child's best interests and preserving, facilitating, and empowering families in these difficult circumstances. But this is an ethical dilemma the child welfare system negotiates daily, and is perhaps the reason used to justify assigning the child welfare system this responsibility. It will also require that the child welfare field have a consensus bioethical paradigm for treatment decision-making for children born with catastrophic illness. Consistent treatment decisions in the best interests of our most vulnerable children cannot be assured, or even expected, without such standardized guidelines.


Formation and Stability of Pea Proteins Nanoparticles Using Ethanol-Induced Desolvation.
Protein nanoparticles have recently found a lot of interests due to their unique physicochemical properties and structure-functionality compared to the conventional proteins. The aim of this research was to synthesize pea protein nanoparticles (PPN) using ethanol-induced desolvation, to determine the changes in secondary structures and the particle stability in an aqueous dispersion. The nanoparticles were prepared by diluting 3.0 wt% pea protein solutions in 1-5 times ethanol at pH 3 and 10 at different temperatures. Higher ratios of ethanol caused greater extent of desolvation and larger sizes of PPN. After homogenization at 5000 psi for 5 min, PPN displayed uniform size distribution with a smaller size and higher zeta potential at pH 10 compared to pH 3. PPN prepared from a preliminary thermal treatment at 95 °C revealed a smaller size than those synthesized at 25 °C. Electron microscopy showed roughly spherical shape and extensively aggregated state of the nanoparticles. Addition of ethanol caused a reduction in β-sheets and an increase in α-helices and random coil structures of the proteins. When PPN were separated from ethanol and re-dispersed in deionized water (pH 7), they were stable over four weeks, although some solubilization of proteins leading to a loss in particle size was observed.


A single-arm study to evaluate the efficacy, safety and acceptability of pericoital oral contraception with levonorgestrel.
An oral dose of 0.75 mg levonorgestrel (LNG) taken shortly after sex was marketed as a routine, nonemergency contraceptive method until the 1990s. Because a hormonal method used only at the time of intercourse may be desirable for women who have infrequent sex, we conducted a study to reevaluate the potential of pericoital LNG as a primary means of contraception. We enrolled women aged 18-45 years in Brazil and the USA who expected to have sex 1-4 days per month for 6.5 months. Participants were instructed to take one tablet 0.75 mg LNG within 24 h before or after sex, with no more than one dose in any 24-h period. The primary efficacy measure was the Pearl Index among women aged 18-35 years. The study was stopped after 72 of the planned 300 participants were enrolled due to slow recruitment and related feasibility considerations. In the primary analysis, three pregnancies occurred during 13.4 woman-years of follow-up, resulting in a Pearl Index of 22.4 (95% confidence interval, 4.6-65.4). No serious adverse events were reported, and vaginal bleeding patterns were generally acceptable. Our estimated Pearl Index was noticeably higher than expected from previous research of LNG for pericoital contraception. Although the regimen was safe and generally acceptable, the study was challenged by slow enrollment and curtailed person-years of follow-up, resulting in poor precision for the estimated treatment effect. Future research may inform whether our results are symptomatic of the regimen, study design or characteristics of the populations from which we recruited. Our study failed to confirm prior data suggesting that 0.75 mg LNG for pericoital contraception could be more effective than typical use of barrier methods among women having infrequent sex. Characterizing populations most likely to adhere to, and benefit from, pericoital regimens is essential to future research on these methods.


[Research progress of knee meniscal repair techniques].
To review the research progress of meniscus repair in recent years, in order to provide help for the clinical decision-making of meniscus injury treatment. The domestic and foreign literature related to meniscal repair in recent years was extensively reviewed to summarize the reasons for the prevalence of meniscal repair, surgical indications, various repair methods and long-term effectiveness, the need to deal with mechanical structural abnormalities, biological enhancement repair technology, rehabilitation treatment, and so on. In order to delay the occurrence of osteoarthritis, the best treatment of meniscus has undergone an important change from partial meniscectomy to meniscal repair, and the indications for meniscal repair have been expanding. The mid- and long-term effectiveness of different meniscal repair methods are ideal. During meniscus repair, the abnormality of lower limb force line and meniscus protrusion should be corrected at the same time. There are controversies about the biological enhancement technology to promote meniscus healing and rehabilitation programs, which need further study. Meniscal repair can restore the normal mechanical conduction of lower limbs and reduce the incidence of traumatic osteoarthritis, but the poor blood supply and healing ability of meniscal tissue bring difficulties to meniscal repair. Further development of new biological enhanced repair technology and individualized rehabilitation program and verification of its effectiveness will be an important research direction.


Short-term inhalation study of graphene oxide nanoplates.
Graphene oxides possess unique physicochemical properties with important potential applications in electronics, pharmaceuticals, and medicine. However, the toxicity following inhalation exposure to graphene oxide has not yet been clarified. Therefore, this study conducted a short-term graphene oxide inhalation toxicity analysis using a nose-only inhalation exposure system and male Sprague-Dawley rats. A total of four groups (15 rats per group) were exposed: (1) control (fresh air), (2) low concentration (0.76 ± 0.16 mg/m3), (3) moderate concentration (2.60 ± 0.19 mg/m3), and (4) high concentration (9.78 ± 0.29 mg/m3). The rats were exposed to graphene oxide for 6 h/day for 5 days, followed by recovery for 1, 3, and 21 days. No significant body or organ weight changes were noted after the short-term exposure or during the recovery period. Similarly, no significant systemic effects of toxicological importance were noted in the hematological assays, bronchoalveolar lavage fluid (BAL) inflammatory markers, BAL fluid cytokines, or blood biochemical assays following the graphene oxide exposure or during the post-exposure observation period. Moreover, no significant differences were observed in the BAL cell differentials, such as lymphocytes, macrophages, or polymorphonuclear cells. Graphene oxide-ingested alveolar macrophages as a spontaneous clearance reaction were observed in the lungs of all the concentration groups from post 1 day to post 21 days. Histopathological examination of the liver and kidneys did not reveal any significant test-article-relevant histopathological lesions. Importantly, similar to previously reported graphene inhalation data, this short-term nose-only inhalation study found only minimal or unnoticeable graphene oxide toxicity in the lungs and other organs.


Complexing agent and heavy metal removals from metal plating effluent by electrocoagulation with stainless steel electrodes.
In the present study, the treatability of a metal plating wastewater containing complexed metals originating from the nickel and zinc plating process by electrocoagulation using stainless steel electrodes was experimentally investigated. The study focused on the effect of important operation parameters on electrocoagulation process performance in terms of organic complex former, nickel and zinc removals as well as sludge production and specific energy consumption. The results indicated that increasing the applied current density from 2.25 to 9.0 mA/cm(2) appreciably enhanced TOC removal efficiency from 20% to 66%, but a further increase in the applied current density to 56.25 mA/cm(2) did not accelerate TOC removal rates. Electrolyte concentration did not affect the process performance significantly and the highest TOC reduction (66%) accompanied with complete heavy metal removals were achieved at the original chloride content ( approximately 1500 mg Cl/L) of the wastewater sample. Nickel removal performance was adversely affected by the decrease of initial pH from its original value of 6. Optimum working conditions for electrocoagulation of metal plating effluent were established as follows: an applied current density of 9 mA/cm(2), the effluent's original electrolyte concentration and pH of the composite sample. TOC removal rates obtained for all electrocoagulation runs fitted pseudo-first-order kinetics very well (R(2)>92-99).


Otolaryngological manifestation of Gorlin Goltz syndrome.
A 46-year-old Jordanian man was seen in ENT clinic complaining of progressive left nasal obstruction and hearing loss for the last five years with a history of multiple surgical removal of dental cysts. Clinical and radiological investigation revealed a cystic mass occupying the left maxillary sinus protruding to the nasal cavity, calcification of the falx cerebri and bifid ribs. On these findings Gorlin-Goltz syndrome was confirmed. The case is presented and the literature reviewed.


Pluripotent Stem Cell-Derived Pancreatic Progenitors and β-Like Cells for Type 1 Diabetes Treatment.
In this review, we focus on the processes guiding human pancreas development and provide an update on methods to efficiently generate pancreatic progenitors (PPs) and β-like cells in vitro from human pluripotent stem cells (hPSCs). Furthermore, we assess the strengths and weaknesses of using PPs and β-like cell for cell replacement therapy for the treatment of Type 1 diabetes with respect to cell manufacturing, engrafting, functionality, and safety. Finally, we discuss the identification and use of specific cell surface markers to generate safer populations of PPs for clinical translation and to study the development of PPs in vivo and in vitro.


Bayesian joint selection of genes and pathways: applications in multiple myeloma genomics.
It is well-established that the development of a disease, especially cancer, is a complex process that results from the joint effects of multiple genes involved in various molecular signaling pathways. In this article, we propose methods to discover genes and molecular pathways significantly associated with clinical outcomes in cancer samples. We exploit the natural hierarchal structure of genes related to a given pathway as a group of interacting genes to conduct selection of both pathways and genes. We posit the problem in a hierarchical structured variable selection (HSVS) framework to analyze the corresponding gene expression data. HSVS methods conduct simultaneous variable selection at the pathway (group level) and the gene (within-group) level. To adapt to the overlapping group structure present in the pathway-gene hierarchy of the data, we developed an overlap-HSVS method that introduces latent partial effect variables that partition the marginal effect of the covariates and corresponding weights for a proportional shrinkage of the partial effects. Combining gene expression data with prior pathway information from the KEGG databases, we identified several gene-pathway combinations that are significantly associated with clinical outcomes of multiple myeloma. Biological discoveries support this relationship for the pathways and the corresponding genes we identified.


A congenital ichthyosiform syndrome with deafness and elevated serum steroid disulphate levels.
This is a report on a child with a syndrome characterized by an extensive congenital ichthyosiform eruption, neurosensory deafness and abnormally elevated serum steroid disulfates neonatally. When analysed by gas-liquid chromatography (glc) and gas chromatography-mass spectrometry (gc-ms) the following serum steroid disulfates were very high 5 days after birth: 5-androstene-3 beta,17 alpha-diol (56 micrograms/ml), 5-androstene-3 beta,17 beta-diol (25 micrograms/ml) and 5-pregnene-3 beta,20 alpha-diol (26 micrograms/ml). The values are about one hundred times higher than the reference values at this age. At the same time serum steroid monosulphate concentrations were normal. The patient had normal steroid sulfatase activity in skin biopsies, indicating that enzyme deficiency was not the reason for the high steroid disulfate concentrations. When serum steroid disulphatases were next analysed at 16 months of age they were normal. No hepatomegaly was observed but the other laboratory data support the hypothesis that the serum steroid disulphate concentrations were due to neonatal hepatography. Later, no indications of chronic liver disease were observed. These indications have not been described earlier in ichthyosiform erythrodermia and it is possible that the patient represents a new type of this rare disease.


Postnatal overnutrition in mice leads to impaired pulmonary mechanics in response to salbutamol.
Obesity increases the risk of respiratory disease, which is associated with airway hyperresponsiveness. Although the molecular underpinnings of this phenomenon are not well established, lung remodeling is known as an important factor in this process and could potentially explain compromised lung functions. In the present study, the obesity was induced by postnatal overnutrition in Swiss mice and we investigated the pulmonary mechanics after aerosolization of saline, methacholine, and salbutamol. The lungs were prepared for morphometric analysis. Obese animals showed bronchoconstriction in response to methacholine, as evidenced by airway and tissue resistance, tissue elastance, and hysteresivity. Salbutamol was effective at recovering the response only for airway resistance but not for tissue mechanics. We suggest that this impaired response in obese mice is related to collapsed alveolar, to inflammatory cells, and to elevated deposition collagen fibers in parenchymal tissue.


Total Synthesis of Sinensilactam A.
The total synthesis of naturally occurring (±)-sinensilactam A was achieved in 18 steps. The key steps of this work are a rhodium-catalyzed [3 + 2] cycloaddition for construction of the two all-carbon vicinal quaternary centers and a convergent and tandem condensation of the in situ generated N-acyliminium intermediate with aldehyde 20. This enabled implementation of a unified strategy for stereoselective formation of the tetracyclic hemiaminal core of sinensilactam A in a later stage. The total syntheses of applanatumol F and C8- epi-applanatumol D are also achieved using this strategy.


CsF-promoted acetyl dance at the narrow rim of p-tert-butyl[188.8.131.52]homooxacalixarene.
In the acetylation of an oxygenated calix[4]arene homologue in the presence of CsF as a base, relaxation of the reaction system to the equilibrium composition takes place through several intra- and intermolecular steps that can be easily controlled to obtain the various acetyl derivatives. The effect of different bases is also discussed.


The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death.
The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ubiquitin ligase which catalyses the generation of linear ubiquitin linkages de novo LUBAC is a crucial component of various immune receptor signalling pathways. Here, we show that LUBAC forms part of the TRAIL-R-associated complex I as well as of the cytoplasmic TRAIL-induced complex II In both of these complexes, HOIP limits caspase-8 activity and, consequently, apoptosis whilst being itself cleaved in a caspase-8-dependent manner. Yet, by limiting the formation of a RIPK1/RIPK3/MLKL-containing complex, LUBAC also restricts TRAIL-induced necroptosis. We identify RIPK1 and caspase-8 as linearly ubiquitinated targets of LUBAC following TRAIL stimulation. Contrary to its role in preventing TRAIL-induced RIPK1-independent apoptosis, HOIP presence, but not its activity, is required for preventing necroptosis. By promoting recruitment of the IKK complex to complex I, LUBAC also promotes TRAIL-induced activation of NF-κB and, consequently, the production of cytokines, downstream of FADD, caspase-8 and cIAP1/2. Hence, LUBAC controls the TRAIL signalling outcome from complex I and II, two platforms which both trigger cell death and gene activation.


Segregated neural representation of distinct emotion dimensions in the prefrontal cortex-an fMRI study.
Emotions are frequently characterized by distinct dimensions such as valence, intensity, and recognition. However, the exact neural representation of these dimensions in different prefrontal cortical regions remains unclear. One of the problems in revealing prefrontal cortical representation is that the very same regions are also involved in cognitive functions associated with emotion processing. We therefore conducted an fMRI study involving the viewing of emotional pictures (using the International Affective Picture System; IAPS) and controlled for associated cognitive processing like judgment and preceding attention. Functional activation was correlated with subjective post-scanning ratings of valence, intensity, and recognition. Valence significantly correlated with the functional response in ventromedial prefrontal cortex (VMPFC) and dorsolateral prefrontal cortex (DLPFC), intensity with activation in ventrolateral prefrontal cortex (VLPFC) and dorsomedial prefrontal cortex (DMPFC), and recognition with the functional response in perigenual anterior cingulate cortex (PACC). In conclusion, our results indicate segregated neural representation of the different emotion dimensions in different prefrontal cortical regions.


Recreational amitriptyline abuse.
Amitriptyline is a potent anticholinergics, rarely used as a drug of abuse. Two cases of amitriptyline dependency lasting for almost twelve months were described. According to the patients the abuse with amitriptyline guarantee them safety not to be uncovered by parents and doctors who systematically checked their urine with typical narcotic tests. Two patients with a history of abuse with amphetamine and clonazepam were admitted to the Clinic because of intoxication with amitriptyline. They denied the suicidal attempt and explained that they used amitriptyline in a dosage of 100 to 200 mg per day as a drug of abuse. On the day of admission one of the patients had increased the dosage up to 600 mg which caused an acute intoxication. Antidepressants should be treated as a drugs with possible abuse ability.


Beyond clients and servers.
Computer scientists working in medical informatics have to face the problem that software offered by industry is more and more adopted for clinical use by medical professionals. A new challenge arises of how to combine commercial solutions with typical medical software that already exists for some years and proved to be reliable with these off-the-shelf solutions [1]. With the HERMES project, this new challenge was accepted and possible solutions to integrate existing legacy systems with state-of-the-art commercial solutions have been investigated. After a period of prototyping to assess possible alternative solutions, a system based on an indirect client-server model was implemented with help of the industry. In this paper, its architecture is described together with the most important features currently covered. Based on the HERMES architecture, both systems for clinical data analysis and patient care (cardiology) are currently developed.


Nebulized hypertonic saline to prevent ventilator associated pneumonia in premature infants, a randomized trial.
Ventilator associated pneumonia (VAP) is a leading cause of death. Nebulized hypertonic saline solution (HSS) has been used to improve pulmonary clearance and reduce infection in intubated patients. This study examines whether nebulized HSS may reduce VAP in intubated premature infants. We analyzed results of 100 intubated premature infants who completed the study. Infants were divided into: (a) the "Control" group, where VAP prevention protocol was implemented and (b) the "Intervention" group, where nebulized HSS twice daily was added to the package of care. Clinical, radiologic, and laboratory evidence of VAP, endotracheal aspirate and blood cultures, and days on mechanical ventilation were compared between groups. VAP occurred in 18% in the intervention group compared to 52% in the control group, relative risk 0.35 (CI:0.18-0.66, p = .001). VAP incidence density was 16/1000 patient-ventilator days in intervention group versus 30/1000 in control group. There was a significant reduction in the days of mechanical ventilation in the intervention group (10.7 ± 8.6 and 16.9 ± 3.4, p < .001). Nebulized HSS may help preserving lung clearance mechanisms and therefore reduce VAP in premature infants. Multi center, double blinded, randomized, controlled, trial is needed to confirm safety and efficacy of such intervention.


Analysis of public policies in favor of the elderly people in Senegal: state of legal protection.
Senegal will be spared by phenomenon of population ageing, which will surely have socioeconomic and cultural consequences that will not be easy to tackle, as all sectors will be affected. In regard to legal protection, there are not any special legal acts for the elderly as is the case for children and women. They are treated just as responsible adults whose legal status is the same as everyone else. As far as the framework of legal protection of elderly people is concerned, Senegal has ratified all international and regional means and mecanisms for the protection of the rights of the elderly. In addition, the authorities have adopted policies and programs that favor taking charge of old people's interests. At the present, Senegal possesses a legal framework for the protection of its elderly people. So the matter is about creating new rights, because even the existing rights are not known to their beneficiaries. What is important is to ensure that the elderly fully enjoy their rights in the same way as the other members of society. It is wise, therefore, to put in place plan for information, public awareness and communication concerning the legal regulating framework. Thus, Senegal could be regarded as a pioneer in terms of the protection the elderly, and these leading programs can represent models for the countries of the region, whose social, sanitary and economic contexts are similar.


Activin/TGFbeta and BMP crosstalk determines digit chondrogenesis.
The progress zone (PZ) is a specialized area at the distal margin of the developing limb where mesodermal cells are kept in proliferation and undifferentiated, allowing limb outgrowth. At stages of digit morphogenesis the PZ cells can undergo two possible fates, either aggregate initiating chondrogenic differentiation to configure the digit blastemas, or to die by apoptosis if they are incorporated in the interdigital mesenchyme. While both processes are controlled by bone morphogenetic proteins (BMPs) the molecular basis for such contrasting differential behavior of the autopodial mesoderm remains unknown. Here we show that a well-defined crescent domain of high BMP activity located at the tip of the forming digits, which we termed the digit crescent (DC), directs incorporation and differentiation of the PZ mesenchymal cells into the digit aggregates. The presence of this domain does not correlate with an exclusive expression domain of BMP receptors and its abrogation by surgical approaches or by local application of BMP antagonists is followed by digit truncation and cell death. We further show that establishment of the DC is directed by Activin/TGFbeta signaling, which inhibits Smad 6 and Bambi, two specific BMP antagonists expressed in the interdigits and progress zone mesoderm. The interaction between Activin/TGFbeta and BMP pathways at the level of DC promotes the expression of the chondrogenic factor SOX9 accompanied by a local decrease in cell proliferation. Characteristically, the DC domain is asymmetric, it being extended towards the posterior interdigit. The presence of the DC is transitorily dependent of the adjacent posterior interdigit and its maintenance requires also the integrity of the AER.


Operating department support level 2 NVQ: Some perceptions.
New roles for support staff are emerging and registered practitioners are now being asked to devolve key aspects of patient care. This study explores some of the background issues relating to these developments and provides evidence regarding the inevitability but also benefits, if managed well, of these changes. The experience of both support staff who have undertaken the Operating Department Support National Vocational Qualification Level 2 (ODS NVQ) and their managers was examined using a phenomenological approach. Data was obtained on the perceived value of this qualification and training and how it affected the working lives and career development of support staff.


Olanzapine in the management of cancer pain.
In cancer patients, cognitive impairment, psychological distress, and anxiety may accompany and aggravate pain. Neuroleptics are frequently used to control these symptoms and may be used to treat pain that has been unresponsive to more conventional approaches. Because of prominent side effects of traditional neuroleptics and conflicting data regarding their analgesic efficacy, their use in the treatment of pain remains controversial. Olanzapine, an atypical neuroleptic, might offer advantages because of its safer side effect profile. It has also been shown to have an independent antinociceptive activity in animals. The use of olanzapine in the management of cancer pain has not been previously described. We prospectively collected the data on 8 cancer patients with severe pain, uncontrolled in spite of aggressive opioid titration, who received olanzapine to treat severe anxiety and mild cognitive impairment. Patients did not meet criteria for delirium and their cognitive impairment was defined as cognitive disorder not otherwise specified (NOS) according to DSM-IV. Patients received 2.5 to 7.5 mg of olanzapine daily. In all patients, opioid requirements had escalated rapidly prior to starting olanzapine. Levels of pain, sedation, and opioid use were measured 2 days before and 2 days after olanzapine was started. Cognitive state was assessed daily. All 8 patients had marked reduction of the daily pain scores. The average daily opioid use decreased significantly in all patients. Cognitive impairment and anxiety resolved within 24 hours of initiating olanzapine. In these 8 patients, decreased pain scores and opioid requirements may have resulted from improvement in cognitive function and the known anxiolytic effect of olanzapine. Other mechanisms may include independent or adjuvant analgesic effects of olanzapine. We conclude that olanzapine may be useful in the treatment of patients with uncontrolled cancer pain associated with cognitive impairment or anxiety. Further studies to evaluate possible analgesic effect of olanzapine are needed.


Examination of substrate and product inhibition kinetics on the production of ethanol by suspended and immobilized cell reactors.
Kinetic expressions for the fermentative production of relatively high concentrations [12% (w/v)] of ethanol have been examined. Several expressions which account for both substrate and product inhibition have been formulated, and have been applied to suspended cell and immobilized cell reactors. Experimental data have been used to validate the kinetic expressions used, and the impact of combined inhibition on optimal reactor configuration has been assessed. The process implications of combined substrate and product inhibition for suspended and immobilized cell systems have been discussed.


Coexpression of atypical chemokine binders (ACBs) in breast cancer predicts better outcomes.
Some evidence suggests that atypical chemokine binders (ACBs) including DARC, D6, and CCX-CKR play an important role in inhibiting invasion and metastasis of cancer cells; however, their expression in breast cancer has not been well characterized. The purpose of this study was to determine the predictive value of ACBs for relapse-free survival and overall survival in breast cancer. The expressions of the three molecules were analyzed immunohistochemically in a total of 558 consecutive breast specimens comprising 12 normal breast tissues, 29 noninvasive (carcinoma in situ), and 517 invasive breast carcinoma and their relationships to clinicopathological features and survival were investigated in invasive breast cancer. Coexpression of ACBs in invasive breast carcinoma (55.9%) was much lower that of noninvasive breast carcinoma (93.1%) and normal breast tissue (100.0%), P = 0.0004, 0.0096, respectively. Their separate stainings in invasive cancer were significantly conversely correlated with lymph node status and tumor stage. In univariate analysis, the three proteins and their coexpression were significantly associated with higher relapse-free survival and overall survival. In multivariate analysis, each of these molecules was favorable for relapse-free survival, but not overall survival. Surprisingly, their coexpression was not only independently prognostic factor for relapse-free survival (RR = 0.182, 95% CI: 0.101-0.327, P < 0.001), but also for overall survival (RR = 0.271, 95% CI: 0.081-0.910, P = 0.035). These findings highlight that the multiple loss of ACBs may occur during the development of tumorigenesis and their coexpression in breast cancer is predictive of favorable outcomes.