Effect of Environmental Enrichment on Aggression in BALB/cJ and BALB/cByJ Mice Monitored by Using an Automated System.
Aggression among mice remains a common undesirable problem in laboratory settings, and animal welfare and scientific outcomes may become compromised depending on the severity of aggression. This study evaluated the effect of cage enrichment comprising a bilevel, mounted 'mezzanine' compared with a cotton square or shelter on intracage male aggression over a 6-wk period. Our first study involved home-cage behavioral challenges to male mice from a high aggression substrain (BALB/cJ) and low-aggression substrain (BALB/cByJ). Aggressive interactions and locomotor activity were scored manually and then compared with measures of activity obtained by using a continuous automated home-cagemonitoring system, the Digital Ventilated Caging (DVC) system. BALB/cJ mice exhibited similar levels of aggression acrosshousing conditions, whereas BALB/cByJ mice had lower aggression when housed with a mezzanine. In the second study,videorecordings and continuous DVC automated measures were collected over 24 h and divided into 12-h light and dark phases. BALB/cByJ mice-but not BALB/cJ-mice had increased aggressive behaviors during the dark phase. However, the DVC detected higher activity levels during the dark phase, compared with the light phase, in both substrains. Elevated activity levels recorded by the DVC correlated with fighting bouts and high levels of locomotion. These results show that a bilevel structural form of enrichment reduces aggression, depending on the BALB/c substrain, and confirms higher aggression levels in the BALB/cJ substrain. In addition, our findings provide evidence that the DVC is effective in identifying mouse cages with patterns of high activity levels, signaling possible aggression incidences, thus potentially allowing for early intervention and consequently improving animal welfare.


Special considerations in the initiation and management of antiretroviral therapy in individuals coinfected with HIV and hepatitis C.
Although hepatitis C (HCV) treatment efficacy has improved in recent years, the majority of HIV/HCV-coinfected individuals may not enjoy the full benefits of these treatments and appropriate HIV management is crucial. Evidence is accumulating regarding the impact of HIV/HCV coinfection on the response to, and safety and tolerability of, antiretroviral therapy (ART) in this population. Computerized, English-language literature searches of MEDLINE and PubMed databases (January 1985 to May 2004) for studies of HIV and HCV infection in humans to examine critically (a) the impact of HCV on the HIV virologic and immunologic response to ART; (b) the safety and tolerability of ART in coinfected individuals; and (c) the relationship between immune suppression and immune restoration on hepatic injury. Three key messages emerged regarding the use of ART in HIV/HCV-coinfected individuals: (a) although HCV appeared to have no impact on HIV virologic response, the data are equivocal regarding immunologic response; (b) morbidities associated with HCV infection, such as insulin resistance, diabetes, mitochondrial dysfunction, and liver inflammation, are also associated toxicities of ART, and (c) both immune suppression and restoration can contribute to the onset and acceleration of HCV-related liver disease. The CD4 cell count threshold for initiating ART in HIV/HCV-coinfected patients may be higher because of the impact of immune suppression and restoration on the onset of HCV-associated liver disease and the possibility of a blunted immune response to ART at lower CD4 cell counts. Further, overlapping morbidity between HCV-related mitochondrial and metabolic disease manifestations and ART toxicities warrant careful attention by clinicians.


Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma.
PPARalpha, beta/delta, and gamma regulate genes involved in the control of lipid metabolism and inflammation and are expressed in all major cell types of atherosclerotic lesions. In vitro studies have suggested that PPARs exert antiatherogenic effects by inhibiting the expression of proinflammatory genes and enhancing cholesterol efflux via activation of the liver X receptor-ABCA1 (LXR-ABCA1) pathway. To investigate the potential importance of these activities in vivo, we performed a systematic analysis of the effects of PPARalpha, beta, and gamma agonists on foam-cell formation and atherosclerosis in male LDL receptor-deficient (LDLR(-/-)) mice. Like the PPARgamma agonist, a PPARalpha-specific agonist strongly inhibited atherosclerosis, whereas a PPARbeta-specific agonist failed to inhibit lesion formation. In concert with their effects on atherosclerosis, PPARalpha and PPARgamma agonists, but not the PPARbeta agonist, inhibited the formation of macrophage foam cells in the peritoneal cavity. Unexpectedly, PPARalpha and PPARgamma agonists inhibited foam-cell formation in vivo through distinct ABCA1-independent pathways. While inhibition of foam-cell formation by PPARalpha required LXRs, activation of PPARgamma reduced cholesterol esterification, induced expression of ABCG1, and stimulated HDL-dependent cholesterol efflux in an LXR-independent manner. In concert, these findings reveal receptor-specific mechanisms by which PPARs influence macrophage cholesterol homeostasis. In the future, these mechanisms may be exploited pharmacologically to inhibit the development of atherosclerosis.


Risk factors for the development of osteoporosis and osteoporotic fractures among older men.
Osteoporotic fractures are associated with significant morbidity and mortality particularly among older men. However, there is little information regarding risk factors among this population. The aims of our study were to determine risk factors for osteoporosis and fragility fractures and the predictive value of bone mineral density (BMD) measurements for development of fragility fractures in a cohort of elderly Caucasian and African American men. We evaluated 257 men aged 70 years or older for risk factors for osteoporosis and fragility fractures using a detailed questionnaire and BMD assessment. Exclusion criteria included conditions known to cause osteoporosis such as hypogonadism and chronic steroid use, current treatment with bisphosphonates, bilateral hip arthroplasties, and inability to ambulate independently. Age, weight, weight loss, androgen deprivation treatment, duration of use of dairy products, exercise, and fracture within 10 years prior to study entry were associated with osteoporosis (p < or = 0.05). Fragility fractures were associated with duration of use of dairy products, androgen deprivation treatment, osteoporosis, and history of fracture within 10 years prior to BMD assessment (p < or = 0.05). There were some differences in risk factors between the Caucasian and African American populations, suggesting that risk factors may vary between ethnic groups. Although men with osteoporosis had a higher rate of fractures, the majority of fractures occurred in men with T-scores > -2.5 standard deviations below the mean, suggesting that factors other than BMD are also important in determining risk.


Influence of ultrasound-to-delivery interval and maternal-fetal characteristics on validity of estimated fetal weight.
To explore the effects of ultrasound-to-delivery interval and maternal-fetal characteristics on the distribution of measurement error in estimated fetal weights (EFWs), and to determine the predictive ability of EFW for diagnosis of small-for-gestational age (SGA) and large-for-gestational age (LGA) among infants delivered within 1 day of an ultrasound examination. Percentage differences between EFW and birth weights were calculated in 3697 pregnancies. Linear regression was used to compare the accuracy of EFW for births on each of the 6 days after an ultrasound scan with the accuracy observed among births on the same day. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value for diagnosis of SGA and LGA according to EFW was assessed. The mean +/- SD percentage difference among deliveries within 1 day of the last ultrasound scan was 0.2 +/- 9.0%. Mean percentage differences were not significantly different from day 0 on days 1, 2 and 3; however, combining the data from these 4 days obscured a slight bias towards an overestimation of weight evident on day 0 and day 1. Among deliveries within 1 day of an ultrasound scan, the PPV was 61% for SGA diagnosis and 54% for LGA diagnosis. Combining data from births > 1 day after the last ultrasound examination may lead to a false conclusion that there is systematic underestimation of weight. EFW tended to underestimate the weight of macrosomic fetuses and overestimate that of small fetuses which limited sensitivity and PPV. Maternal-fetal characteristics are weak predictors of individual errors in EFW.


[Interpretation for the group standard of the General principles of description for pathogenic microorganism collection].
Pathogenic microorganism is an important national strategic resource, whose value is embodied in the physical object and its corresponding information and data resources. At present, China has basically completed the designation of national and provincial preservation centers and professional laboratories, and various preservation institutions have been put into operation and begun to play its role of preservation institutions. In order to standardize the data management of pathogenic microorganism preservation and improve the quality of pathogenic microorganism resources, China CDC took the lead in formulating and issuing the community standard of Chinese Preventive Medicine Association, the General principles of description for pathogenic microorganism collection (T/CPMA 011-2020). The standard puts forward the data fields and description principles of microorganism strain, including general data such as number, name, separation, hazard classification, transmission route, pathogenicity, and characteristic data such as virus, bacteria and fungi. The core of pathogenic microorganism resources lies in quality and the foundation lies in standards. Taking data standards as the starting point, it will play an important supporting role in promoting the transformation of pathogenic microorganism preservation work to quality improvement, improving resource sharing and utilization, and leading the sustainable development of preservation work.


"It's all interconnected… like a spider web": a qualitative study of the meanings of food and healthy eating in an Indigenous community.
Canadian Indigenous populations are disproportionately affected by rising rates of diet-related chronic disease and have been experiencing rapid lifestyle changes affecting diet. In recognition of these issues, this study aimed to obtain greater understanding of attitudes and meanings around healthy eating in a semi-remote community in Eeyou Istchee. A qualitative study design used semi-structured interviews and observational field notes to explore local accounts of food and health. Two distinct versions of "healthy eating" were identified: one relating to traditional food and preparation methods; the other reflecting medicalised accounts of illness and diagnosed conditions. The latter links with "southern" modes of accessing and preparing food, demonstrating local capacity to adapt to the rapid changes in body, lifestyle and environment being experienced. New connections, associating non-native ways with traditional practices, are being formed where traditional ways of living on the land have been severed. These local accounts show how people are continually negotiating different constructs of "healthy eating." These findings expand current understandings of the context of food and healthy eating in Eeyou Istchee, emphasising present-day and historical experiences of the land. Future research and diet-related health interventions must continue to acknowledge and incorporate local understandings of health to help address the broader socio-political factors that shape Indigenous lifestyles, environments and health.


Herbal/Plant Remedies and Supplements Used by Hispanics/Latinxs for Diabetes: Source of Functional Foods?
The purpose of this study was to explore the use of herbal/plant remedies and supplements for type 2 diabetes (T2DM) among Hispanics/Latinxs in North Carolina and identify demographic and diabetes-related factors associated with use of these therapies. Baseline data from a family-based diabetes intervention tailored for Hispanics/Latinxs were analyzed using descriptive statistics, bivariate analyses, and logistic regression. A convenience sample of 186 adults with T2DM and adult family members with and without T2DM was recruited from community-based settings and data obtained from face-to-face interviews conducted in Spanish. Most participants were female (73%) with an average age of 45 years old. Among this predominantly immigrant sample (96%), 78% of participants reported being from Mexico. Sixty percent had T2DM, and average A1C was 8.7% for persons with T2DM. Nearly a third reported using 51 different remedies for diabetes management. Most ingested them concurrently with prescribed medications; however, 11.3% reported altering the dose of medications when using herbal/plant remedies or supplements. Most common items were prickly pear cactus, pineapple, celery, aloe vera, parsley, and spinach. Using herbs/plants was positively correlated with age, A1C, and years with T2DM. The odds of using herbs/plants increased 28% for every 1% increase in A1C (adjusted odds ratio = 1.28, P = .003). Asking about herbal/plant remedy and supplement use is important. Although there is limited efficacy and safety studies for some items, multiple reported remedies are functional foods with biologically active ingredients to promote health. Patient education is needed on safe and unsafe items and use with prescribed medications.


Astrobiology - an opposing view.
The use of quantum computers and Artificial Intelligence (AI) is imperative for use in space exploration and astrobiology investigations. Considerable progress has been made since the commencement of origin of life laboratory and theoretical studies in the mid 20th century. However, the sheer amount of data amassed to date in all these studies including exoplanetary and astrobiological studies is enormous and increasing steadily. Thus, there is the need for AI and quantum computers. As AI develops, it will become crucial in the development of the statistical and database programs that are indispensable to analyze the huge quantity of cumulative data. Diverse biotic and geochemical processes have been shown to produce methane on the Earth. Elsewhere in the solar system, on other planets (e.g. Mars) and moons (e.g. Titan), as well as on exoplanets, abiotic processes are considered the primary sources of methane. Astronomers and astro-biologists infer that the presence of methane supports the possibility of the presence of at least microbial life. In addition, on the Earth, there are also degradative reactions that include smog-related compounds and hazes that are produced as artefacts of intrinsic methane geochemistry as well as due to human footprint. Astronomers and astro-biologists envision life, away from the Earth, elsewhere in the solar system and on exoplanets, to occur under conditions similar or related to terrestrial life (goldilocks zone) conditions. These properties that are compatible with life as we know it on the Earth, include planetary orbits, gravitation, star radiant energy, presence of liquid water, and compatible temperatures and pressures, found on Earth. Generally, extraterrestrial life is also considered to resemble the biochemistry, molecular biology, and physiology of life on Earth - thus the focus on detection of supposed biosignatures of microbial life that resemble the Earth's. Nevertheless a crucial factor is absent in these deliberations - viruses. On the Earth, viruses that infect Archaea and bacteria form local and widespread global ecosystems. These viruses play a crucial role and facilitate the molecular transfer of host genes among various hosts. This essential function is underestimated in evolutionary as well as astrobiological speculations. Thus, it is of substantial importance to consider the roles that viruses may have played during the origin of life as well as in any exobiology.


Detection of gyrA and parC mutations associated with ciprofloxacin resistance in Neisseria gonorrhoeae by use of oligonucleotide biochip technology.
An oligonucleotide biochip that specifically detects point mutations in the gyrA and parC genes of Neisseria gonorrhoeae was designed and subsequently evaluated with 87 untreated clinical specimens. The susceptibilities of the N. gonorrhoeae strains were tested to determine the prevalence of ciprofloxacin-resistant strains in Anhui Province, People's Republic of China. Conventional DNA sequencing was also performed to identify mutations in gyrA and parC and to confirm the biochip data. The study demonstrates that all of the point mutations in the gyrA and parC genes of N. gonorrhoeae were easily discriminated by use of the oligonucleotide biochip. Fifteen different alteration patterns involved in the formation of ciprofloxacin resistance were identified by the biochip assay. Double mutations in both Ser91 and Asp95 of the GyrA protein were seen in all nonsensitive isolates. Double mutations in Ser91 and Asp95 of GyrA plus mutation of Glu91 or Ser87 of the ParC protein lead to significant high-level resistance to ciprofloxacin in N. gonorrhoeae isolates. The results obtained by use of the oligonucleotide biochip were identical to those obtained by use of DNA sequencing. In conclusion, the oligonucleotide biochip technology has potential utility for the rapid and reliable identification of point mutations in the drug resistance genes of N. gonorrhoeae.


Net renal extraction of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine in fasting humans.
Recently, the potential importance of dimethylarginines as endogenously produced inhibitors of nitric oxide synthase has become clearer. Interestingly, elevated levels have been reported in patients with vascular disease, but especially in patients suffering end-stage renal disease. Although the kidney obviously seems to play a key role in the elimination of dimethylarginines, clear insight into the renal handling of these compounds is lacking. Thus, our aim was to investigate the renal extraction of dimethylarginines. Plasma concentrations of dimethylarginines were determined in both arterial and renal venous blood in 20 fasting patients with normal renal function. Renal extraction was calculated as the arteriovenous concentration difference divided by the arterial concentration times 100%. A significant renal extraction was found for both dimethylarginines. Renal extraction was significantly higher for asymmetrical dimethylarginine (ADMA) when compared with symmetrical dimethylarginine (SDMA) (16.2 vs 10.5% respectively, P=0.001). In addition, arterial SDMA concentration, but not ADMA concentration, significantly correlated with arterial creatinine concentration. In healthy humans, the kidney contributes to the regulation of plasma levels of dimethylarginines, since both ADMA and SDMA were significantly extracted from the arterial supply. Interestingly, a higher renal extraction of ADMA was found when compared to SDMA extraction, which strongly suggests the presence of an additional catabolic pathway for ADMA in the kidney.


Left atrial anatomical variations correlate with atrial fibrillation sources near the left atrial ridge.
Anatomical variations and characteristics of the left atrium (LA) may have a previously undescribed effect on source locations in atrial fibrillation (AF). This is the first study aiming to investigate the relationship between anatomical characteristics of the LA and non-PV sources detected by electrographic flow (EGF) mapping in patients with persistent AF. We analyzed cardiac computed tomography (CT) and EGF mapping data in patients who underwent radiofrequency catheter ablation (CA). EGF mapping is a novel method based on Horn-Schunk flow estimation algorithm, used to estimate cardiac action potential flow in the atria that can detect AF sources in patients with persistent AF. By analyzing EGF maps obtained during CA procedures, we localized non-PV sources in the LA. Thirty patients were included in this study (mean age 62.4 ± 6.8 years). Ten patients had AF sources near the LA ridge, while twenty patients had no leading source (source activity > 26%) near the LA ridge. LA anatomical characteristics, left atrial appendage (LAA) length, and ostial diameter showed no correlation with the presence of a leading source. We documented 19 patients with abutting LAA and left superior pulmonary vein (LSPV) (distance < 2 mm), and 11 patients with non-abutting LAA-LSPV (distance > 2 mm). Three out of 19 patients presented with a leading source near ridge in the abutting LAA-LSPV group, while 7 out of 11 patients presented with a leading source near the ridge in the non-abutting LAA-LSPV group (p = 0.01). Our data suggests that non-abutting LAA-LSPV is associated with the presence of AF sources near the LA ridge.


Electrophysiological (CNV) analysis of personality traits under stress.
Contingent negative variation (CNV) recordings were performed in 55 healthy volunteers under stress condition (experimentally induced pain). A total of 20 subjects were included in the control group (no painful administration). In the tested group (n = 35) the painful stimulus was delivered before S1, between S2 and S1, and before S2. In the control group there were no changes in CNV parameters. Conversely, among the tested group a positive correlation was found between CNV values (whenever the painful stimulus was administered before S1 as well as before S2) and the highest scores in the State Trait Anxiety Inventory X 2 test. In addition, all individuals displayed the appearance of a positive deflection with a latency of about 300 ms from S2 when the experimental stress was given before S2. Furthermore, the postimperative negative variation (PINV) appeared in 13 out of 35 subjects. There was a strong correlation between the latter electrophysiological phenomenon and the Nowlis test. Our findings suggest that CNV study is useful for the investigation of personality traits in human beings under stress conditions.


Needlestick-prevention devices. Disposable syringes and injection needles.
Needlestick-prevention devices (NPDs) are an essential tool for protecting healthcare workers from injuries that could result in exposure to bloodborne pathogens. More than a dozen NPD varieties are available. They generally take the same form as conventional (nonsafety) sharps but incorporate some type of safety design--for example, a shield or a needle-retracting mechanism. In this Evaluation, we focus on protective devices that are used in place of conventional syringes and injection needles--namely, disposable protective syringes and needle guards. We tested 14 products from 8 suppliers. We give Preferred ratings to three products, all of which are needle-retracting syringes. When used correctly, these devices provide the best protection available. However, their primary safety advantage--preremoval activation--can be negated if the user chooses to activate the safety mechanism after removing the needle from the patient. For many facilities, one of the seven models we rate Acceptable might be a better choice. We caution that our ratings should not be the sole basis of a purchase decision. Staff members need to conduct a hands-on assessment of the available products to identify those that best meet their needs. We also stress that any NPD--even one we rate Not Recommended--is preferable to using no protective device at all.


Tracker-Based Personal Advice to Support the Baby's Healthy Development in a Novel Parenting App: Data-Driven Innovation.
The current generation of millennial parents prefers digital communications and makes use of apps on a daily basis to find information about child-rearing topics. Given this, an increasing amount of parenting apps have become available. These apps also allow parents to track their baby's development with increasing completeness and precision. The large amounts of data collected in this process provide ample opportunity for data-driven innovation (DDI). Subsequently, apps are increasingly personalized by offering information that is based on the data tracked in the app. In line with this, Philips Avent has developed the uGrow app, a medical-grade app dedicated to new parents for tracking their baby's development. Through so-called insights, the uGrow app seeks to provide a data-driven solution by offering parents personal advice that is sourced from user-tracked behavioral and contextual data. The aim of this study was twofold. First, it aimed to give a description of the development process of the insights for the uGrow app. Second, it aimed to present results from a study about parents' experiences with the insights. The development process comprised 3 phases: a formative phase, development phase, and summative phase. In the formative phase, 3 substudies were executed in series to understand and identify parents' and health care professionals' (HCPs) needs for insights, using qualitative and quantitative methods. After the formative phase, insights were created during the development phase. Subsequently, in the summative phase, these insights were validated against parents' experience using a quantitative approach. As part of the formative phase, parents indicated having a need for smart information based on a data analysis of the data they track in an app. HCPs supported the general concept of insights for the uGrow app, although specific types of insights were considered irrelevant or even risky. After implementing a preliminary set of insights in a prototype version of the uGrow app and testing it with parents, the majority of parents (87%) reported being satisfied with the insights. From these outcomes, a total of 89 insights were implemented in a final version of the uGrow app. In the summative phase, the majority of parents reported experiencing these insights as reassuring and useful (94%), as adding enjoyment (85%), and as motivating for continuing tracking for a longer period of time (77%). Parents experienced the insights in the uGrow app as useful and reassuring and as adding enjoyment to their use of the uGrow app and tracking their baby's development. The insights development process we followed showed how the quality of insights can be guaranteed by ensuring that insights are relevant, appropriate, and evidence based. In this way, insights are an example of meaningful DDI.


HCV testing and treatment initiation in an Italian prison setting: A step-by-step model to micro-eliminate hepatitis C.
HCV infection among vulnerable populations is currently a major issue for HCV elimination program. Incarcerated people and people who inject drugs (PWIDs) are key population groups potentially at high risk for HCV infection. Our aim was to evaluate an extended program of screening, staging and treatment in Italian prison settings. Patients from eight prisons in five different Italian Regions were enrolled. HCV saliva test (QuickOral Test®) was offered. Data on infection awareness and illicit drug use were also collected. Positive patients underwent early HCV RNA evaluation, staging and prescription on DAAs treatment. The definition of PWID was based on self-reported injecting drug use extracted from medical records (injecting drug use during the previous six months). A total of 2,376 out of 2,687 individuals (88%) was tested. The median (IQR) age was 42 (32-50) years. PWIDs were 537out of 2,376 (23%). Prevalence of HCV antibodies was 10.4% (248/2,376). PWIDs had a lower awareness of their HCV-Ab positivity than non-PWIDs (p-value <0.001). Furthermore, PWIDs were less likely to be previously treated than non-PWIDs (78% vs 96%, p-value= 0.017). Active infection was found in 41% of patients (101/248). Overall, 61% HCV-positive were PWIDs, with 44% HCV RNA positive. HCV therapy was prescribed to 83% (84/101) of patients with active HCV infection and 67% of these (56/84) were PWIDs. Prescription for HCV treatment in PWIDs accounted for 84% (56/67) (while for non-PWIDs was 82% (28/34) p-value: 0.88. Seventeen patients were referred to a Specialist in other prisons because they were going to be transferred soon to another prison. EOT, as well as SVR12 were achieved in 98% (82/84) treated patients. Among patients, PWIDs had a lower awareness of their HCV-Ab positivity and had previously received less treatments. Saliva test allowed to achieve a more rapid result, stage, and treatment approach. More than 80% of patients underwent treatment, without differences between PWIDs and non-PWIDs. Linkage to care during prison transfer allowed to avoid unplanned interruptions and offered more chances to reach the end of treatment.


Can statins put the brakes on Alzheimer's disease?
Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which initiates the syntheses of cholesterol and isoprenoid lipids that are needed to provide amyloid peptides for the amyloid cascade. This cascade is believed to induce sporadic or late-onset Alzheimer's disease, which accounts for 90 - 95% of Alzheimer's disease sufferers. Cholesterol is also the prime driver of cerebrovascular disease that (along with amyloid peptides) increasingly appears to be linked to the cognitive deterioration of Alzheimer's disease. Cholesterol is needed to make the lipid rafts that are the platforms for isoprenoid-dependent assembly and activation of raftophilic beta- and gamma-secretases that work in tandem to excise dangerous 40 and 42 amino acid amyloid-beta (Abeta) fragments from amyloid precursor protein, the transmembrane amyloid precursor glycoprotein. When they are excessively produced and can no longer be effectively destroyed or otherwise cleared from the hypoperfused ageing brain, the Abeta42 fragments released from the active synaptic terminals of normally busy neurons (and from stressed neurons unsuccessfully trying to proliferate and producing disruptive tangles of hyperphosphorylated tau-proteins) aggregate into neuritic plaques, which activate glial cells. The pro-inflammatory cytokines and growth factors from the glial cells further damage and kill neurons. As statins strike at several parts of the Alzheimer's disease mechanism (such as the infliction of cholesterol-dependent cerebrovascular damage) by inhibiting HMG-CoA reductase, their long-term use (starting as early as possible during Alzheimer's disease development) should slow or even prevent the progression of Alzheimer's disease. Indeed, there is some evidence of a significantly reduced incidence of Alzheimer's disease among people who have been using statins to reduce hypercholesterolaemia and its cardiovascular effects. To be certain of this, there must be more multi-year trials to specifically assess the effects of statins on sporadic Alzheimer's disease.


[Clinical observations in vascular occlusion of kidney tumors by absolute alcohol].
The results of the occlusion of renal tumors by two different materials-Ethibloc (n = 26) and absolute alcohol (n = 72) are being compared. The kidneys were occluded under equal clinical conditions. The clinical symptoms following embolisation are fewer in the group of alcohol embolized patients than in the group with Ethibloc. On the capillary level, the histological reaction to alcohol corresponds to a histotoxic alteration. This reaction goes beyond the reactive inflammation of the tissue observed after Ethibloc. This intensified reaction of the tissue after alcohol application partially explains the advantage of a fractionated application of alcohol during tumor embolisation.


Does Trypsin Oral Spray (Viruprotect®/ColdZyme®) Protect against COVID-19 and Common Colds or Induce Mutation? Caveats in Medical Device Regulations in the European Union.
nasal or oral sprays are often marketed as medical devices (MDs) in the European Union to prevent common cold (CC), with ColdZyme®/Viruprotect® (trypsin/glycerol) mouth spray claiming to prevent colds and the COVID-19 virus from infecting host cells and to shorten/reduce CC symptoms as an example. We analyzed the published (pre)-clinical evidence. preclinical: comparison of in vitro tests with validated host cell models to determine viral infectivity. Clinical: efficacy, proportion of users protected against virus (compared with non-users) and safety associated with trypsin/glycerol. preclinical data showed that exogenous trypsin enhances SARS-CoV-2 infectivity and syncytia formation in host models, while culture passages in trypsin presence induce spike protein mutants. The manufacturer claims >98% SARS-CoV-2 deactivation, although clinically irrelevant as based on a tryptic viral digest, inserting trypsin inactivation before host cells exposure. Efficacy and safety were not adequately addressed in clinical studies or leaflets (no COVID-19 data). Protection was obtained among 9-39% of users, comparable to or lower than placebo-treated or non-users. Several potential safety risks (tissue digestion, bronchoconstriction) were identified. the current European MD regulations may result in insufficient exploration of (pre)clinical proof of action. Exogenous trypsin exposure even raises concerns (higher SARS-CoV-2 infectivity, mutations), whereas its clinical protective performance against respiratory viruses as published remains poor and substandard.


Fescue-associated oedema of horses grazing on endophyte-inoculated tall fescue grass (Festuca arundinacea) pastures.
A new form of toxicity called equine fescue oedema is described. The clinical signs included inappetence, depression, and subcutaneous oedema of the head, neck, chest and abdomen. Affected horses had very low plasma albumin values. The toxicity affected 48 of 56 horses on six farms in different states of Australia, and 4 horses have died. All horses were grazing pastures that had been sown with varieties of Mediterranean tall fescue (Festuca arundinacea) that carry the endophyte known as Max P or Max Q. It is proposed that a pyrrolizidine alkaloid, N-acetyl norloline, which is produced by the Max P endophyte, may be responsible for this new toxicity in horses.


On the Method of Pulse-Heated Analysis of Solid Reactions (PHASR) for Polyolefin Pyrolysis.
The continued need for plastics necessitates an effective solution for processing and recycling polymer wastes. While pyrolysis is a promising technology for polyolefin recycling, an experimental apparatus must be designed to measure the intrinsic kinetics and elucidate the chemistry of the plastics pyrolysis process. To resolve this issue, a modified Pulse-Heated Analysis of Solid Reactions (PHASR) system was designed, constructed, and evaluated for the purposes of polyolefin pyrolysis. Experimental results demonstrated that the new PHASR system is capable of measuring the millisecond-resolved evolution of plastic [e. g., low-density polyethylene (LDPE)] pyrolysis products at a constant temperature. The PHASR system was shown to be capable of producing a repeatable, fast heating time (20 ms) and cooling time (130-150 ms), and of maintaining a stable temperature during reaction. A second, Visual PHASR system was developed to enable high-speed photography and visualization of the real-time pyrolysis of LDPE.


Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2.
In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells' expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.


Therapeutic Potential of Adipose Stem Cell-Derived Conditioned Medium on Scar Contraction Model.
Scars are composed of stiff collagen fibers, which contract strongly owing to the action of myofibroblasts. To explore the substances that modulate scar contracture, the fibroblast-populated collagen lattice (FPCL) model has been used. However, the molecular signature of the patient-derived FPCL model has not been verified. Here, we examined whether the patient-derived keloid FPCL model reflects scar contraction, analyzing detailed gene expression changes using comprehensive RNA sequencing and histological morphology, and revealed that these models are consistent with the changes during human scar contracture. Moreover, we examined whether conditioned media derived from adipose stem cells (ASC-CM) suppress the scar contracture of the collagen disc. Detailed time-series measurements of changes in disc area showed that the addition of ASC-CM significantly inhibited the shrinkage of collagen discs. In addition, a deep sequencing data analysis revealed that ASC-CM suppressed inflammation-related gene expression in the early phase of contraction; in the later phase, this suppression was gradually replaced by extracellular matrix (ECM)-related gene expression. These lines of data suggested the effectiveness of ASC-CM in suppressing scar contractures. Therefore, the molecular analysis of the ASC-CM actions found in this study will contribute to solving medical problems regarding pathological scarring in wound prognosis.


Electroconvulsive therapy in the presence of a metallic skull plate after meningioma resection.
Electroconvulsive therapy (ECT) is an effective and safe treatment even in the frail and in the medically ill. A case report of ECT being administered to a patient with a history of a recently resected meningioma and the presence of a metallic skull plate is presented here. The patient has a history of bipolar disorder in remission but had an acute manic episode with psychotic features after resection of suprasellar meningioma. He presented with superimposed delirium that complicated the presentation. Because there was no effective resolution with medications, ECT was administered. This case documents the safe administration of ECT in complicated situations such as these. This case also demonstrates that ECT can be successfully administered in the presence of superimposed delirium and after a recent meningioma resection. Clinical skills and expertise are required to safely and effectively administer ECT in such cases.


Workplace smoking ban effects on unhappy smokers.
Economists usually draw a distinction between smokers. They distinguish 'happy addicts' à la Becker-Murphy from 'unhappy addicts' who state that smoking is a mistake and call for some help to quit. When evaluating tobacco control policies, it might be important to distinguish their effects on those two types of population. Indeed, such policies are welfare improving only if they help unhappy addicts to quit. We investigate the effect of the French workplace smoking ban on a sample of presumably 'unhappy addicts', smokers who consult tobacco cessation services. We show that the ban caused an increase in the demand for such services, and that this increase was larger in cold and rainy areas. It also induced an increase in the percentage of successful attempts to quit. Workplace smoking bans might be welfare improving since they seem to help 'unhappy addicts' to reconcile their behavior with their preferences.


Involvement of the dopaminergic and serotonergic systems in the antidepressant-like effect caused by 4-phenyl-1-(phenylselanylmethyl)-1,2,3-triazole.
The study investigated the antidepressant-like effect and acute toxicity of 4-phenyl-1-(phenylselanylmethyl)-1,2,3-triazole (Se-TZ), an organoselenium-containing heterocycle compound in mice. The antidepressant-like effect of Se-TZ (1-50mg/kg) and its mechanism of action, was analyzed in the tail suspension test (TST) in male C57BL/6J mice. Additionally, the levels of the monoamines and their metabolites in cerebral cortex and hippocampus were analyzed by high-performance liquid chromatography. To investigate the potential acute toxicity caused by Se-TZ, the mice received a single oral dose of Se-TZ (1-50mg/kg), and after 72h were performed the assays. The Se-TZ (5-50mg/kg) significantly reduced immobility time in TST without altering locomotor and exploratory activities. The antidepressant-like effect of Se-TZ (25mg/kg) in the TST was prevented by pre-treatment of mice with SCH23390, sulpiride and methysergide, but not with prazosin, yohimbine and propranolol. Se-TZ, increased monoamine neurotransmitters dopamine and serotonin levels in the cerebral cortex and hippocampus, whereas norepinephrine turnover was not changed. This study also demonstrated that the Se-TZ, did not cause the acute toxicity in biochemical markers hepatic and renal investigated. The results evidenced that exposure to Se-TZ caused a significant increase in the catalase (CAT) activity in the cerebral cortex and hippocampus, however the glutathione S-transferase (GST) activity increased only in the cerebral cortex. These results suggest that Se-TZ demonstrated antidepressant-like effect, mediated via the central dopaminergic and serotoninergic neurotransmitter systems which may be of interest as a therapeutic agent for the treatment of depressive disorders.


[Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart].
To explore the effects of ischemic postconditioning on ischemia/reperfusion injury in isolated hypertrophied rat heart and investigate the signal transduction pathway changes induced by ischemia postconditioning. Cardiac hypertrophy was induced in rats by abdominal aortic banding, and isolated hypertrophied rat heart ischemia/reperfusion model was made by Langendorff technique to evaluate the effects of ischemia postconditioning on left ventricular systole pressure, coronary artery flow, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) release, myocardial infarction size, and the level of myocardial phospho-protein kinase B/Akt (Ser473), phospho-glycogen synthase kinase-3beta (Ser9). Following groups were studied (n = 12 each group): IR, 30 min ischemia (I)/60 min Reperfusion (R); Post: 30 min ischemia, 6 circles of 10 s I/10 s R followed by 60 min R; Post Wort: 30 min ischemia, 6 circles of 10 s I/10 s R, wortmannin (10(-7) mol/L) followed by 60 min R; Wort: 30 min ischemia, wortmannin (10(-7) mol/L) followed by 60 min R. Left ventricular systolic pressure and coronary artery flow were significantly increased, myocardial infarction size and the release of CPK, LDH significantly reduced in Post group compared to that in IR group. Phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) levels were also significantly higher in Post group than that in IR group. Phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin prevented the increase of phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) induced by ischemic postconditioning, but only partly abolished the cardioprotection of ischemic postconditioning. Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart. The cardioprotective effects of ischemic postconditioning were partly mediated through PI3K/Akt/GSK-3beta signaling pathway.


Marine Sponge is a Promising Natural Source of Anti-SARS-CoV-2 Scaffold.
The current pandemic caused by SARS-CoV2 and named COVID-19 urgent the need for novel lead antiviral drugs. Recently, United States Food and Drug Administration (FDA) approved the use of remdesivir as anti-SARS-CoV-2. Remdesivir is a natural product-inspired nucleoside analogue with significant broad-spectrum antiviral activity. Nucleosides analogues from marine sponge including spongouridine and spongothymidine have been used as lead for the evolutionary synthesis of various antiviral drugs such as vidarabine and cytarabine. Furthermore, the marine sponge is a rich source of compounds with unique activities. Marine sponge produces classes of compounds that can inhibit the viral cysteine protease (Mpro) such as esculetin and ilimaquinone and human serine protease (TMPRSS2) such as pseudotheonamide C and D and aeruginosin 98B. Additionally, sponge-derived compounds such as dihydrogracilin A and avarol showed immunomodulatory activity that can target the cytokines storm. Here, we reviewed the potential use of sponge-derived compounds as promising therapeutics against SARS-CoV-2. Despite the reported antiviral activity of isolated marine metabolites, structural modifications showed the importance in targeting and efficacy. On that basis, we are proposing a novel structure with bifunctional scaffolds and dual pharmacophores that can be superiorly employed in SARS-CoV-2 infection.


(Not) Home alone: Antigen presenting cell - T Cell communication in barrier tissues.
Priming of T cells by antigen presenting cells (APCs) is essential for T cell fate decisions, enabling T cells to migrate to specific tissues to exert their effector functions. Previously, these interactions were mainly explored using blood-derived cells or animal models. With great advances in single cell RNA-sequencing techniques enabling analysis of tissue-derived cells, it has become clear that subsets of APCs are responsible for priming and modulating heterogeneous T cell effector responses in different tissues. This composition of APCs and T cells in tissues is essential for maintaining homeostasis and is known to be skewed in infection and inflammation, leading to pathological T cell responses. This review highlights the commonalities and differences of T cell priming and subsequent effector function in multiple barrier tissues such as the skin, intestine and female reproductive tract. Further, we provide an overview of how this process is altered during tissue-specific infections which are known to cause chronic inflammation and how this knowledge could be harnessed to modify T cell responses in barrier tissue.


Comparative proteomic analysis of grain development in two spring wheat varieties under drought stress.
Two spring wheat varieties Ningchun 4 and Chinese Spring with good and poor resistance to abiotic stress, respectively, were used to investigate proteomic changes in the developing grains under drought stress by a comparative proteomics approach. A total of 152 protein spots showed at least twofold differences in abundance on two-dimensional electrophoresis (2-DE) maps, of which 28 and 68 protein spots were identified by MALDI-TOF and MALDI-TOF/TOF mass spectrometry, respectively. Of the 96 identified protein spots, six different expression patterns were found and they were involved in stress/defense/detoxification, carbohydrate metabolism, photosynthesis, nitrogen metabolism, storage proteins and some other important functions. Comparative proteomic analysis revealed that under the drought conditions the decreased degree of ascorbate peroxidases was more significant in Chinese Spring than in Ningchun 4 during grain development whereas translationally controlled tumor protein, which was significantly upregulated at 14 DAF, was present in Ningchun 4 and absent in Chinese Spring. The Rubisco large subunit displayed an upregulated expression pattern in Ningchun 4. In addition, two drought-tolerant proteins, triosephosphate isomerase and oxygen-evolving complex showed B and F type expression patterns in Chinese Spring, but D and B types in Ningchun 4, respectively. These differentially expressed proteins might be responsible for the stronger drought resistance of Ningchun 4 compared to Chinese Spring.


Patients with acute lymphoblastic leukaemia allografted with a matched unrelated donor may have a lower survival with a peripheral blood stem cell graft compared to bone marrow.
We analysed data for 213 patients with ALL and AML who received either peripheral blood stem cells (PBSC) (n=74) or bone marrow (BM) (n=139) from an HLA-matched unrelated donor (EBMT acute leukaemia registry; January 1994 to January 1999). The two groups of patients (by cell source) were comparable with respect to age, sex, disease status, year at transplant and graft T cell depletion. Engraftment was achieved in about 90% regardless of stem cell source or leukaemia type. Kinetics of neutrophil and platelet recovery, similar for both sources in ALL patients, were faster for PBSC in AML patients. The incidence of acute graft-versus-host disease was similar for both sources in AML patients, but higher for PBSC in ALL patients (74 vs 54%, P=0.05). The 1-year probability of chronic graft-versus-host disease was 40 and 45% (P=0.66) in ALL patients compared to 49 and 35% (P=0.13) in AML patients (PBSC vs BM). In AML patients, none of the following differed significantly with cell source: transplant-related mortality, relapse incidence, leukaemia-free survival and overall survival. In ALL patients, the transplant-related mortality for PBSC vs BM was 61 vs 47% (P=0.13), the relapse incidence was 47 vs 39% (P=0.17), the leukaemia-free survival was 21 vs 32% (P=0.04) and the overall survival was 24 vs 34% (P=0.04). These data suggest that the short-term outcome of allogeneic PBSC is not significantly different from that of BM in AML patients who underwent a transplant from a matched unrelated donor but, conversely, that survival with PBSC may be decreased in ALL patients. In conclusion, the source of transplant cells needs to be evaluated by disease, especially when dealing with unrelated donors.


Chemoselective ligation in the functionalization of polysaccharide-based particles.
Despite the promise of precisely targeted or otherwise functionalized polymeric particulate drug delivery vehicles, typical biocompatible particles are generally not amenable to facile and selective surface modification. Herein, we report the development of a simple, mild, and chemoselective strategy for the conjugation of biologically active molecules to the surface of dextran-based microparticles. Alkoxyamine-bearing reagents were used to form stable oxime conjugates with latent aldehyde functionality present in reducing carbohydrate chain ends. We demonstrate the functionalization of dextran-based microparticles with a fluorophore as well as a cell-penetrating peptide sequence, which facilitated the delivery of cargo to nonphagocytic cells leading to a 60-fold increase in the expression of a reporter gene when plasmid DNA-loaded particles were used.


Imaging appearance of myelopathy secondary to nitrous oxide abuse: a case report and review of the literature.
Purpose The abuse of nitrous oxide (N2O) can induce Vitamin B12 deficiency that subsequently leads to central nervous demyelination, myelopathy and peripheral neuropathy. Although myelopathy has been reported in the past, the specific locations and prognosis of the disease are still unclear. We report the case of a 22-year-old male who presented with quadriplegia that began after a 3-month history of inhalation of N2O. We summarized the clinical data of this entity and performed a comprehensive literature review of various presentations and MRI features of myelopathy secondary to N2O abuse. In combination with previous reports of 14 cases, we found that the onset of the disease was usually subacute, and the majority of patients (92.85%) were young men. There was no definite relationship between myelopathy and the amount or duration of N2O inhalation. The most common clinical manifestation was sensory ataxia, and the cervical spinal cord was the most frequently impaired area of the whole spinal cord. The spinal cord lesions had a high signal intensity on T2-weighted MRI and usually involved more than three spinal segments and impaired the posterior column more significantly. Most patients recovered well after vitamin B12 supplementation. Myelopathy secondary to N2O abuse is generally seen in young men. The clinical diagnosis mainly depends on a history of N2O inhalation and the characteristic imaging changes in the posterior cervical spinal cord. Early diagnosis and intervention are important for a satisfactory prognosis.


Reducing Inpatient Length of Stay Using a Multicollaborative Protocol for Management of Non-Intensive Care Unit Asthmatics.
Maximizing clinical efficiency through the reduction in inpatient length of stay (LOS) using standardized protocols has been a major objective among hospital administrators, most notably in the context of recent healthcare reimbursement changes at statewide levels. The objective of our project was to determine whether a synchronous change in an inpatient asthma protocol that relied on a respiratory therapist (RT)-driven bronchodilator weaning algorithm and bronchodilator therapy given through a metered dose inhaler (MDI) plus valved holding chamber (VHC) could impact clinical and financial outcomes. A pre-post study assessed patients aged 2-21 years of age admitted with a primary diagnosis of status asthmaticus. The effect of the protocol was measured from October 2014 to July 2015. Outcome variables included patient demographics, hospital LOS, all-patient refined diagnosis-related groups (APR-DRGs), and inpatient charges. Outcomes were compared between the preimplementation and postimplementation time periods. Statistical significance was measured using Wilcoxon signed-rank test and bootstrap logistic regression models. Protocol patients (n = 110) had a similar demographic and clinical profile compared with the matched population from the previous nonprotocol fiscal year (n = 150). Use of the protocol resulted in a significantly reduced LOS that maintained significance after adjusting for APR-DRGs weight (P < 0.05). The protocol did not alter the total hospital billing charges. A nonstatistically significant reduction in 30-day readmission rates was observed among those administered the protocol. An RT-led weaning protocol using a quantitative scoring system and MDI+VHC for bronchodilator administration resulted in a significantly reduced LOS.


Improved methods for estimating abundance and related demographic parameters from mark-resight data.
Over the past decade, there has been much methodological development for the estimation of abundance and related demographic parameters using mark-resight data. Often viewed as a less-invasive and less-expensive alternative to conventional mark recapture, mark-resight methods jointly model marked individual encounters and counts of unmarked individuals, and recent extensions accommodate common challenges associated with imperfect detection. When these challenges include both individual detection heterogeneity and an unknown marked sample size, we demonstrate several deficiencies associated with the most widely used mark-resight models currently implemented in the popular capture-recapture freeware Program MARK. We propose a composite likelihood solution based on a zero-inflated Poisson log-normal model and find the performance of this new estimator to be superior in terms of bias and confidence interval coverage. Under Pollock's robust design, we also extend the models to accommodate individual-level random effects across sampling occasions as a potentially more realistic alternative to models that assume independence. As a motivating example, we revisit a previous analysis of mark-resight data for the New Zealand Robin (Petroica australis) and compare inferences from the proposed estimators. For the all-too-common situation where encounter rates are low, individual detection heterogeneity is non-negligible, and the number of marked individuals is unknown, we recommend practitioners use the zero-inflated Poisson log-normal mark-resight estimator as now implemented in Program MARK.


Visuospatial orientation in Parkinson's disease.
Visuospatial functioning in patients with Parkinson's disease was investigated using neuropsychological measures of basic visual perception, complex perceptual discrimination, and spatial orientation. Three subgroups of patients were described: (a) those with broadly impaired visuospatial abilities, (b) those with generally intact abilities, and (c) those whose performance on a task of spatial orientation was lower than their performance on a task of complex perceptual discrimination. These subgroup differences were also concordant with three other variables: age, duration of disease, and degree of dementia. It is suggested that decreases in spatial orientation functioning in Parkinson's disease may reflect the speed of progression of this disease.


Greatly increased electrical conductivity of PBTTT-C14 thin film via controllable single precursor vapor phase infiltration.
Doping is an important strategy for effectively regulating the charge carrier concentration of semiconducting materials. In this study, the electronic properties of organic-inorganic hybrid semiconducting polymers, synthesized viain situcontrolled vapor phase infiltration (VPI) of poly[2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene] (PBTTT-C14) with the metal precursors molybdenum pentachloride (MoCl5) and titanium tetrachloride (TiCl4), were altered and characterized. The conductivities of the infiltration-doped PBTTT-C14 thin films were enhanced by up to 9 and 4 orders of magnitude, respectively. The significantly improved electrical properties may result from interactions between metal atoms in the metal precursors and sulfur of the thiophene rings, thus forming new chemical bonds. Importantly, VPI doping has little influence on the structure of the PBTTT-C14 thin films. Even if various dopant molecules infiltrate the polymer matrix, the interlayer spacing of the films will inevitably expand, but it has negligible effects on the overall morphology and structure of the film. Also, Lewis acid-doped PBTTT-C14 thin films exhibited excellent environmental stability. Therefore, the VPI-based doping process has great potential for use in processing high-quality conductive polymer films.


Well-Known and Novel Serum Biomarkers for Risk Stratification of Patients with Non-ischemic Dilated Cardiomyopathy.
Non-ischemic dilated cardiomyopathy encompasses a wide spectrum of myocardial disorders, characterized by left ventricular dilatation with systolic impairment and increased risk of sudden cardiac death. In spite of all the therapeutic progress that has been made in recent years, dilated cardiomyopathy continues to be an important cause of cardiac transplant, being associated with an enormous cost burden for health care systems worldwide. Predicting the prognosis of patients with dilated cardiomyopathy is essential to individualize treatment. Late gadolinium enhancement-cardiac magnetic resonance imaging, microvolt T-wave alternans, and genetic testing have emerged as powerful tools in predicting sudden cardiac death occurrence and maximizing patient's selection. Despite all these new diagnostic modalities, additional tests to complement or replace current tools are required for better risk stratification. Therefore, biomarkers are an easy and important tool that can help to detect patients at risk of adverse cardiovascular events. Additionally, identifying potential biomarkers involved in dilated cardiomyopathy can provide us important information regarding the diagnostic, prognostic, risk stratification, and response to treatment for these patients. Many potential biomarkers have been studied in patients with dilated cardiomyopathy, but only a few have been adopted in current practice. Therefore, the aim of our review is to provide the clinicians with an update on the well-known and novel biomarkers that can be useful for risk stratification of patients with non-ischemic dilated cardiomyopathy.


Enhancing Light-Driven 1,3-Propanediol Production by Using Natural Compartmentalization of Differentiated Cells.
Synthetic biology emerges as a powerful approach for unlocking the potential of cyanobacteria to produce various chemicals. However, the highly oxidative intracellular environment of cyanobacteria is incompatible to numerous introduced enzymes from anaerobes. In this study, we explore a strategy based on natural compartmentalization of cyanobacterial heterocysts to overcome the incompatibility. Hence, the oxygen-sensitive 1,3-propanediol (1,3-PDO) biosynthetic pathway was selected as a model and insulated in heterocysts to evaluate the proposed strategy. Thus, the genes from different sources for 1,3-PDO production were tandemly arrayed with promoter, resulting the assembled 1,3-PDO synthetic cassettes. Then the synthetic cassettes were integrated into the chromosome of Anabaena sp. strain PCC7120 by homologous recombination, respectively. The engineered strain P11 containing the genes from facultative anaerobe Klebsiella pneumoniae (cassette KP) accumulated 46.0 mg L-1 of 1,3-PDO when heterocysts were present, which is approximately 1.7-fold higher than that of no heterocysts. As for the strains (P12, P13, and P14) containing the genes from strictly anaerobic bacterium Clostridium butyricum (cassette CB), the product 1,3-PDO could only be detected when heterocysts were present. These results indicate that insulation of the oxygen-sensitive 1,3-PDO pathway with heterocysts is an effective way to protect these enzymes in cyanobacteria. The strategy may have the potential of serving as a universal strategy to overcome the incompatibility of oxygen-sensitivity in synthetic biology.


Dual Inhibition of H3K9me2 and H3K27me3 Promotes Tumor Cell Senescence without Triggering the Secretion of SASP.
Chemotherapy remains the most common cancer treatment. Although chemotherapeutic drugs induce tumor cell senescence, they are often associated with post-therapy tumor recurrence by inducing the senescence-associated secretory phenotype (SASP). Therefore, it is important to identify effective strategies to induce tumor cell senescence without triggering SASP. In this study, we used the small molecule inhibitors, UNC0642 (G9a inhibitor) and UNC1999 (EZH2 inhibitor) alone or in combination, to inhibit H3K9 and H3K27 methylation in different cancer cells. Dual inhibition of H3K9me2 and H3K27me3 in highly metastatic tumor cells had a stronger pro-senescence effect than either inhibitor alone and did not trigger SASP in tumor cells. Dual inhibition of H3K9me2 and H3K27me3 suppressed the formation of cytosolic chromatin fragments, which inhibited the cGAS-STING-SASP pathway. Collectively, these data suggested that dual inhibition of H3K9 and H3K27 methylation induced senescence of highly metastatic tumor cells without triggering SASP by inhibiting the cGAS-STING-SASP pathway, providing a new mechanism for the epigenetics-based therapy targeting H3K9 and H3K27 methylation.


Pathological changes in horses dying with equine influenza in Australia, 2007.
Analysis of pathology results from the 2007 equine influenza (EI) outbreak in Australia indicate that young foals in naïve horse populations are prone to developing broncho-interstitial pneumonia, and that this can be a rare manifestation of EI virus infection in mature horses. All horses may develop secondary bacterial bronchopneumonia, with mature horses more likely to die. EI outbreaks among heavily pregnant mares can result in increased neonatal losses because of premature placental separation and dystocia causing fetal hypoxia.


[Dysmorphophobia in dentistry].
Patients suffering from dysmorphophobia with symptoms involving the masticatory system, i. e. teeth, mouth and jaws, were subjected to comprehensive examinations in close cooperation with the psychiatric profession. In rare cases the problem underlying the urgent desire for treatment in difficult patients is a disease known as dysmorphophobia. The signs of this disease that become evident in the dental office and the specific personality features of the patients affected are described and demonstrated in three typical case reports. Our experience has shown that irreversible and isolated dental manipulations are to be avoided. An interdisciplinary treatment objective (besser: approach?) integrating dental treatment into a greater therapeutic context is proposed.


Identification of the null HLA-A2 allele, A*0232N.
We have identified a null HLA-A*02 allele, HLA-A*0232N, by using a combination of serology, flow cytometry, polymerase chain reaction using sequence-specific primers (PCR-SSP) and full-length sequencing. The null HLA-A2 allele was identified in an Asian individual originally typed by serology as an apparently homozygous HLA-A3, B51. Subsequent genotyping by PCR-SSP identified the genotype as HLA-A*0201, *0301, B*51, Cw*1402. The serological type and lack of detectable HLA-A2 was confirmed using monoclonal antibody typing reagents. Flow cytometry studies failed to identify any cell surface HLA-A2 expression on the patient's peripheral blood lymphocytes. Genotyping using a PCR-SSP set designed to detect null alleles revealed the mutation had not been previously described. Full-length sequencing of the allele identified an allele which was subsequently named HLA-A*0232N. This allele is identical to HLA-A*0201 except for a novel point mutation (T for C) at position 493 which creates a premature stop codon. The sequencing enabled the development of a monospecific A*0232N PCR-SSP reaction which was used to screen 973 DNA samples: no further examples of A*0232N were identified.


On use of the variable connectivity index 1chi(f) in QSAR: toxicity of aliphatic ethers.
The number of non-hydrogen atoms in a molecule, N, appears as a very good molecular descriptor for the toxicity of aliphatic ethers, despite the fact that it does not differentiate among isomers. The regression based on N as a descriptor for the toxicity in mice of 21 alkyl ethers was reported to yield the regression coefficient r = 0.9751. The simple connectivity index 1chi produced for the same data a less satisfactory regression: r = 0.9548. To see if variable connectivity index 1chi(f) can improve the regression characterized by N we examined the same data using the variable connectivity index 1chi(f) as a molecular descriptor. By varying x, y, the variables that discriminate between carbon and oxygen atoms, we obtained regression which approaches in quality the best reported regression using weighted paths as descriptor and which is marginally better than the regression based on N.


Are all multisubunit tethering complexes bona fide tethers?
Since the late 1990s, a number of multisubunit tethering complexes (MTCs) have been described that function in membrane trafficking events: TRAPP I, TRAPP II, TRAPP III, COG, HOPS, CORVET, Dsl1, GARP and exocyst. On the basis of structural and sequence similarities, they have been categorized as complexes associated with tethering containing helical rods (CATCHR) (Dsl1, COG, GARP and exocyst) or non-CATCHR (TRAPP I, II and III, HOPS and CORVET) complexes (Yu IM, Hughson FM. Tethering factors as organizers of intracellular vesicular traffic. Annu Rev Cell Dev Biol 2010;26:137-156). Both acronyms (CATCHR and MTC) imply these complexes tether opposing membranes to facilitate fusion. The main question we will address is: have these complexes been formally demonstrated to function as tethers? If the answer is no, then is it premature or even correct to refer to them as tethers? In this commentary, we will argue that the vast majority of MTCs have not been demonstrated to act as a tether. We propose that a distinction between the terms tether and tethering factor be considered to address this issue.


Modified metasurface Alvarez lens based on the phase compensation in a microwave band.
Alvarez lenses, a kind of passive zoom lenses with reconfigurable focus, have been widely applied in optics but very few at lower frequencies such as in a microwave band, where the phase approximation for Alvarez lenses becomes inaccurate. In this article, we propose a design of a modified Alvarez lens with phase compensation for microwave, which consists of a pair of transmissive metasurfaces with high efficiency. The proposed metasurface consists of miniaturized units with the capability of full 2π phase modulation. We further analyze the phase distribution principle of the Alvarez lens and proposed a phase compensation scheme. The simulation results confirm that the proposed modified Alvarez lens has a very good dynamic focal length with theoretical expectation and can be continuously adjusted from 100 to 200 mm.


Epigenetic reprogramming of H3K27me3 and DNA methylation during leaf-to-callus transition in peach.
Plant tissues are capable of developing unorganized cell masses termed calluses in response to the appropriate combination of auxin and cytokinin. Revealing the potential epigenetic mechanisms involved in callus development can improve our understanding of the regeneration process of plant cells, which will be beneficial for overcoming regeneration recalcitrance in peach. In this study, we report on single-base resolution mapping of DNA methylation and reprogramming of the pattern of trimethylation of histone H3 at lysine 27 (H3K27me3) at the genome-wide level during the leaf-to-callus transition in peach. Overall, mCG and mCHH were predominant at the genome-wide level and mCG was predominant in genic regions. H3K27me3 deposition was mainly detected in the gene body and at the TSS site, and GAGA repetitive sequences were prone to recruit H3K27me3 modification. H3K27me3 methylation was negatively correlated with gene expression. In vitro culture of leaf explants was accompanied by DNA hypomethylation and H3K27me3 demethylation, which could activate auxin- and cytokinin-related regulators to induce callus development. The DNA methylation inhibitor 5-azacytidine could significantly increase callus development, while the H3K27me3 demethylase inhibitor GSK-J4 dramatically reduced callus development. These results demonstrate the roles of DNA methylation and H3K27me3 modification in mediating chromatin status during callus development. Our study provides new insights into the epigenetic mechanisms through which differentiated cells acquire proliferative competence to induce callus development in plants.


Kate o'hanlon 1930-2014.
Former sister of the emergency department at the Royal Victoria Hospital, Belfast, Kate O'Hanlon has died. Described as 'an outstanding nurse and a distinguished member' of the Royal College of Nursing (RCN), Ms O'Hanlon began her general nurse training at the Royal Victoria Hospital in 1958. Once she had completed this training, she moved to Liverpool to train as a midwife and then returned to Belfast to work as a district midwife in the Docklands area of the city.


CPC, a single-repeat R3 MYB, is a negative regulator of anthocyanin biosynthesis in Arabidopsis.
Single-repeat R3 MYB transcription factors like CPC (CAPRICE) are known to play roles in developmental processes such as root hair differentiation and trichome initiation. However, none of the six Arabidopsis single-repeat R3 MYB members has been reported to regulate flavonoid biosynthesis. We show here that CPC is a negative regulator of anthocyanin biosynthesis. In the process of using CPC to test GAL4-dependent driver lines, we observed a repression of anthocyanin synthesis upon GAL4-mediated CPC overexpression. We demonstrated that this is not due to an increase in nutrient uptake because of more root hairs. Rather, CPC expression level tightly controls anthocyanin accumulation. Microarray analysis on the whole genome showed that, of 37 000 features tested, 85 genes are repressed greater than three-fold by CPC overexpression. Of these 85, seven are late anthocyanin biosynthesis genes. Also, anthocyanin synthesis genes were shown to be down-regulated in 35S::CPC overexpression plants. Transient expression results suggest that CPC competes with the R2R3-MYB transcription factor PAP1/2, which is an activator of anthocyanin biosynthesis genes. This report adds anthocyanin biosynthesis to the set of programs that are under CPC control, indicating that this regulator is not only for developmental programs (e.g. root hairs, trichomes), but can influence anthocyanin pigment synthesis.


Outcomes and surgical therapeutic index of Burch colposuspension in stress urinary incontinence.
To apply the new concept of a surgical therapeutic index to patients who suffer from stress urinary incontinence using the cure rate and complication rates of Burch colposuspension and to develop a preoperative counseling tool and objective comparison tool for the many surgical procedures that have been described. We reviewed the case histories of 22 patients between March 1999 and March 2000 who had stress urinary incontinence and underwent Burch colposuspension and in whom the diagnosis of stress urinary incontinence was made using urodynamic studies and the cotton-tipped-swab test. The surgical therapeutic index was then calculated using the median percentage cure rate and complication rate. The surgical cure rates were 81.8%, 81.8%, 90.9%, 90.9%, 95.4% and 95.4% at postoperative 1st, 3rd, 5th, 7th, 9th and 12th month, respectively, and the surgical complication rates were 69%, 36%, 31.5%, 27%, 22.5% and 27%. The surgical therapeutic indices for each postoperative period were 1.19, 2.27, 2.89, 3.37, 4.24 and 3.53, respectively. The surgical cure rate for Burch colposuspension in stress urinary incontinence was 95.4% 1 year after surgery, and the surgical therapeutic index 1 month and 1 year after surgery was 1.19 and 3.53, respectively. Burch colposuspension is a relatively effective and safe surgical procedure for managing stress urinary incontinence.


The N-acetylglutamate synthase/N-acetylglutamate kinase metabolon of Saccharomyces cerevisiae allows co-ordinated feedback regulation of the first two steps in arginine biosynthesis.
In Saccharomyces cerevisiae, which uses the nonlinear pathway of arginine biosynthesis, the first two enzymes, N-acetylglutamate synthase (NAGS) and N-acetylglutamate kinase (NAGK), are controlled by feedback inhibition. We have previously shown that NAGS and NAGK associate in a complex, essential to synthase activity and protein level [Abadjieva, A., Pauwels, K., Hilven, P. & Crabeel, M. (2001) J. Biol. Chem.276, 42869-42880]. The NAGKs of ascomycetes possess, in addition to the catalytic domain that is shared by all other NAGKs and whose structure has been determined, a C-terminal domain of unknown function and structure. Exploring the role of these two domains in the synthase/kinase interaction, we demonstrate that the ascomycete-specific domain is required to maintain synthase activity and protein level. Previous results had suggested a participation of the third enzyme of the pathway, N-acetylglutamylphosphate reductase, in the metabolon. Here, genetic analyses conducted in yeast at physiological level, or in a heterologous background, clearly demonstrate that the reductase is dispensable for synthase activity and protein level. Most importantly, we show that the arginine feedback regulation of the NAGS and NAGK enzymes is mutually interdependent. First, the kinase becomes less sensitive to arginine feedback inhibition in the absence of the synthase. Second, and as in Neurospora crassa, in a yeast kinase mutant resistant to arginine feedback inhibition, the synthase becomes feedback resistant concomitantly. We conclude that the NAGS/NAGK metabolon promotes the co-ordination of the catalytic activities and feedback regulation of the first two, flux controlling, enzymes of the arginine pathway.


Evaluation of the efficacy of gallium maltolate for chemoprophylaxis against pneumonia caused by Rhodococcus equi infection in foals.
To determine the chemoprophylactic effect of gallium maltolate on the cumulative incidence of pneumonia caused by Rhodococcus equi infection in foals. 483 foals born and raised on 12 equine breeding farms with a history of endemic R equi infections. Group 1 foals were treated with a placebo and group 2 foals were treated with gallium maltolate (approx 30 mg/kg, PO, q 24 h) during the first 2 weeks after birth. Foals were monitored for development of pneumonia attributable to R equi infection and for adverse effects of gallium maltolate. There were no significant differences in the cumulative incidence of R equi pneumonia among the 2 groups. Chemoprophylaxis via gallium maltolate administered orally at approximately 30 mg/kg daily for the first 2 weeks after birth failed to reduce the cumulative incidence of pneumonia attributable to R equi infection among foals on breeding farms with endemic R equi infections. Further investigation is needed to identify strategies for control of R equi infections.


[Haemophilus influenzae type b: epidemiological situation in the State of Minas Gerais, Brazil, 1993-1997].
Among Haemophilus influenzae type b (Hib) invasive diseases, pneumonia and meningitis are the most relevant in public health due to their frequency and severity. From 1993 to 1997, there were 720 cases of Hib meningitis in Minas Gerais State, Brazil, representing the most frequent cause of bacterial meningitis in infants (< 1 year) and the second most frequent among all causes of meningitis. The total estimated cases of invasive Hib diseases thus appear to justify the recent inclusion of the vaccine in the basic immunization protocol. The vaccine's high cost reinforces the need for more precise monitoring of the etiological diagnosis of meningitis cases, representing one of the weaknesses in the prevailing epidemiological surveillance system.


Discovery of potent and selective inhibitors of human platelet-type 12- lipoxygenase.
We report the discovery of novel small molecule inhibitors of platelet-type 12-human lipoxygenase, which display nanomolar activity against the purified enzyme, using a quantitative high-throughput screen (qHTS) on a library of 153607 compounds. These compounds also exhibit excellent specificity, >50-fold selectivity vs the paralogues, 5-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity vs ovine cyclooxygenase-1 and human cyclooxygenase-2. Kinetic experiments indicate this chemotype is a noncompetitive inhibitor that does not reduce the active site iron. Moreover, chiral HPLC separation of two of the racemic lead molecules revealed a strong preference for the (-)-enantiomers (IC(50) of 0.43 ± 0.04 and 0.38 ± 0.05 μM) compared to the (+)-enantiomers (IC(50) of >25 μM for both), indicating a fine degree of selectivity in the active site due to chiral geometry. In addition, these compounds demonstrate efficacy in cellular models, which underscores their relevance to disease modification.


Evaluation of the Genetic Association and Expressions of Notch-2 /Jagged-1 in Patients with Type 2 Diabetes Mellitus.
Diabetes mellitus (DM) is the world's most common cause of chronic kidney diseases (CKD), with approximately 1 in 4 adults with DM having CKD and 1 out of 10 to 20% of DM patients die from CKD. The current study aims to investigate the correlation between Notch-2 and Jag-1expressions and specific inflammation biomarkers IL-1β and IL-6 with different stages of diabetic nephropathy. From August 2018 to January 2019, three hundred subjects were recruited for this study. One hundred and fifty subjects were healthy and age-matched to the diabetic group and selected as a control group. Another 150 patients with an established diagnosis of type 2 diabetes (T2DM) according to the criteria of the American Diabetes Association (ADA) were also recruited. Blood specimens were eventually used to identify the expressions Notch-2 and Jagged-1 and the levels of inflammatory biomarkers IL-1β and IL-6. The current study shows a significant increase in gene expression and inflammatory biomarkers in patients with moderate and severe diabetic nephropathy compared to the control group. However, there was no significant difference between healthy control and mild diabetic nephropathy patients. This study shows a close association between the increase in the levels of inflammatory biomarkers IL-1β and IL-6 as well as the gene expressions levels of both Notch-2 and Jag-1 with human diabetic nephropathy. According to our findings, we emphasize the use of Notch-2 and Jag-1 expressions and IL-1β and IL-6 levels as potential biomarkers for different stages of diabetic nephropathy.


A transferrinlike (hemiferrin) mRNA is expressed in the germ cells of rat testis.
In the testis, germ cells which are separated from the serum by the blood-testis barrier rely primarily on the Sertoli cell to obtain nutrients. For example, transferrin synthesized by the Sertoli cell is important in delivering iron from the serum to the developing germ cells. Because of its role in the testis, Sertoli cell transferrin protein and mRNA have been extensively studied. By using RNA blot analysis of rat testicular tissue, we detected a transcript of 2.6 kb which is attributed to transferrin. In addition, we detected a novel mRNA of 0.9 kb which had sequence similarity to the 3' end of transferrin. This 0.9-kb mRNA was present in germ cells, but not Sertoli cells, liver, or brain. The primary source of this mRNA in the testis was round spermatids. Sequence analysis of a cDNA clone showed that this mRNA encoded a protein with sequence similarity to the carboxy terminus of transferrin. Polysome analysis indicated that this transcript was translated and may therefore have importance in the iron metabolism of germ cells. The evolutionary implications between the transferrinlike mRNA germ cells and the gene duplication event which resulted in the diferric binding of transferrin are discussed.


A common supersolid skin covering both water and ice.
Consistency in experimental observations, numerical calculations, and theoretical predictions have revealed that the skins of water and ice share the same attribute of supersolidity characterized by an identical H-O vibration frequency of 3450 cm(-1). Molecular undercoordination and inter-electron-pair repulsion shortens the H-O bond and lengthens the O:H nonbond, leading to a dual process of nonbonding electron polarization. This relaxation-polarization process enhances the dipole moment, elasticity, viscosity, and thermal stability of these skins with a 25% density loss, which is responsible for the hydrophobicity and toughness of the water skin and results in the slippery behavior of ice.


p53 controls choice between apoptotic and non-apoptotic death following DNA damage.
DNA damage can activate apoptotic and non-apoptotic forms of cell death; however, it remains unclear what features dictate which type of cell death is activated. We report that p53 controls the choice between apoptotic and non-apoptotic death following exposure to DNA damage. In contrast to the conventional model, which suggests that p53-deficient cells should be resistant to DNA damage-induced cell death, we find that p53-deficient cells die at high rates following DNA damage, but exclusively using non-apoptotic mechanisms. Our experimental data and computational modeling reveal that non-apoptotic death in p53-deficient cells has not been observed due to use of assays that are either insensitive to cell death, or that specifically score apoptotic cells. Using functional genetic screening - with an analysis that enables computational inference of the drug-induced death rate - we find in p53-deficient cells that DNA damage activates a mitochondrial respiration-dependent form of cell death, called MPT-driven necrosis. Cells deficient for p53 have high basal respiration, which primes MPT-driven necrosis. Finally, using metabolite profiling, we identified mitochondrial activity-dependent metabolic vulnerabilities that can be targeted to potentiate the lethality of DNA damage specifically in p53-deficient cells. Our findings reveal how the dual functions of p53 in regulating mitochondrial activity and the DNA damage response combine to facilitate the choice between apoptotic and non-apoptotic death.


Varying molecular interactions by coverage in supramolecular surface chemistry.
The possibility of modifying the intermolecular interactions of absorbed benzene-carboxylic acids from coordination to hydrogen bonding by changing their surface coverage is demonstrated through a combination of scanning tunnelling microscopy, X-ray photoemission spectroscopy and density functional theory calculations.


Subcorneal pustular dermatosis in the pediatric age.
Subcorneal pustular dermatosis is a rare pustular eruption which occurs mainly in middle-aged women and rarely during childhood. We report a case of a 15-year-old female with a 4-year history of pustular lesions on the proximal region of the upper limbs with subsequent impairment of the trunk. Physical examination revealed small pustules distributed on the trunk and proximal region of the limbs. Histopathology showed a subcorneal pustule and direct immunofluorescence for IgA, IgM, IgG and fibrinogen was negative, confirming the diagnosis of subcorneal pustular dermatosis. The patient was treated with dapsone with good clinical response after one month. Subcorneal pustular dermatosis is a rare condition and there are only isolated cases reported in the literature in pediatric patients. Thus, we discuss the main clinical aspects and treatment response of this condition during childhood.


Long-term performance of untreated fresh autologous pericardium as a valve substitute in pulmonary position.
Pulmonary regurgitation is imminent after transannular patch (TAP). We analyze the long-term performance of untreated autologous pericardium (UAP) as valve substitute at pulmonary position in patients requiring TAP. This cross-sectional study include patients operated between 2007 and 2012 (n = 92). A sample of 19 patients was selected for this study which had a follow-up of more than 3 years. This includes patients with no TAP (n = 4) and with TAP and valve substitute, a monocusp (n = 11) or a tricuspid valve (n = 4) at neopulmonary annulus. Patients underwent echocardiography for assessment of right ventricle function and 18 fluoro-deoxyglucose PET CT scan for measurements of valve substitute at neopulmonary annulus. The target to blood ratio (TBR) of uptake of glucose by monocusp was measured at the cooptation edge of the neopulmonary valve. The median age of the patients is 14 (9 - 37). RV function is preserved (TAPSE 18.9 (10.6 - 22.8)) at a mean follow-up of 4 years (3-9). The measurements of monocusp shows a shrinkage in height of the cusp by 35.5% (70% - 1.0%) and length by 7% (-44% - +104%). There was less shrinkage observed in patients below 15 years of age. The TBR of monocusp was 0.945 (0.17 - 3.35) with a strong correlation between the TBR values of aortic valve leaflet and monocusp leaflet of same patient. The UAP is functional and successful as a valve substitute at neo pulmonary annulus at long-term follow-up. It has resisted calcification and has shown uptake of glucose in physiological limits.


Hemodynamic responses among three tracheal intubation devices in normotensive and hypertensive patients.
We compare hemodynamic responses in normotensive and hypertensive anesthetized paralyzed patients among three intubation devices: the Macintosh laryngoscope (LS), the Trachlight lightwand (LW), and the intubating laryngeal mask airway Fastrach (ILM). Seventy-five normotensive and 75 hypertensive patients were randomly assigned to each intubation device (n = 25). Noninvasive systolic blood pressure (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were recorded immediately preinduction, immediately preintubation, and every minute for the first 5 min after the successful intubation. The number of intubation attempts, the time to successful intubation, and any airway injuries were recorded. Pharyngolaryngeal morbidity was assessed 18-24 h after surgery by a blinded investigator. In all groups, there was a reduction in SBP and DBP but no change in HR immediately preintubation compared with baseline values. In all groups, HR increased, but there were no increases in SBP and DBP other than in DBP in the LS/hypertensive group after intubation compared with baseline values. In normotensive patients, there were no differences in any hemodynamic variables among the three devices. In hypertensive patients, SBP and DBP in the LS group were significantly higher than the ILM and LW groups for 2 min after intubation, but there were no differences in HR among the devices. The number of intubation attempts was similar among groups, but intubation time was longer for the ILM group. The incidence of airway injury was more frequent for the ILM than the LS and LW groups (16% versus 0% versus 0%). There were no differences in pharyngolaryngeal morbidity among groups. We conclude that both the ILM and the LW attenuated the hemodynamic stress response to tracheal intubation compared with the LS in hypertensive, but not in normotensive, anesthetized paralyzed patients. Both the intubating laryngeal mask airway Fastrach and the Trachlight lightwand attenuate the hemodynamic stress response to tracheal intubation compared with the Macintosh laryngoscope in hypertensive, but not in normotensive, anesthetized paralyzed patients.


Low-frequency vibrations in resonance Raman spectra of horse heart myoglobin. Iron-ligand and iron-nitrogen vibrational modes.
The low-frequency regions (150--700 cm-1) of resonance Raman (RR) spectra of various complexes of oxidized and reduced horse heart myoglobin were examined by use of 441.6-nm excitation. In this frequency range, RR spectra show 10 bands common to all myoglobin derivatives (numbered here for convenience from I to X). Relative intensities of bands IV, V, and X constitute good indicators of the doming state of the heme and, consequently, of the spin state of the iron atom. An additional band is present for several complexes (fluorometmyoglobin, hydroxymetmyoglobin, azidometmyoglobin, and oxymyoglobin). Isotopic substitutions on the exogenous ligands and of the iron atom (56Fe leads to 54Fe) allow us to assign these additional lines to the stretching vibrations of the Fe-sixth ligand bond. Similarly, bands II are assigned to stretching vibrations of the Fe-N-(pyrrole) bonds. An assignment of bands VI to stretching vibrations of the Fe-Nepsilon(proximal histidine) bonds is also proposed. Mechanisms for the resonance enhancement of the main low-frequency bands are discussed on the basis of the excitation profiles and of the dispersion curves for depolarization ratios obtained for fluorometmyoglobin and hydroxymetmyoglobin.


Jejunal diverticulosis.
Diverticulosis of the jejunum is an uncommon condition. We found four patients with such diverticula among 40,341 hospital admissions. All four patients presented with acute volvulus of the small bowel. It is suggested that the diverticula bearing segment becomes heavier due to the diverticula and the semisolid jejunal contents consisting of roughage, millet and cereals in the staple diet of our patients. Both factors contribute to small bowel volvulus. Jejunal diverticula may be missed because they are buried between the leaves of mesentery or adherent loops of jejunum. With a patient has vague abdominal symptoms, the possibility of jejunal diverticula should be considered.


1:1 Adduct of (S,S)-4-amino-3,5-bis(1-hydroxyethyl)-1,2,4-triazole with (S,S)-1,2-bis(2-hydroxypropionyl)hydrazine stabilized by eight hydrogen bonds.
The structure of the cocrystallized 1:1 adduct of (S,S)-4-amino-3,5-bis(1-hydroxyethyl)-1,2,4-triazole and (S,S)-1,2-bis(2-hydroxypropionyl)hydrazine, C6H12N4O2.C6H12N2O4, has tetragonal symmetry. All eight O- and N-bound H atoms are involved in intermolecular hydrogen bonds, resulting in infinite zigzag chains of the triazole molecules, with the hydrazine molecules filling the gaps between the chains and completing a three-dimensional hydrogen-bonded array.


Intravenous transplantation of olfactory bulb ensheathing cells for a spinal cord hemisection injury rat model.
Cellular transplantation strategies utilizing intraspinal or intrathecal olfactory ensheathing cells (OECs) have been reported as beneficial for spinal cord injury (SCI). However, there are many disadvantages of these methods, including additional trauma to the spinal cord parenchyma and technical challenges. Therefore, we investigated the feasibility and potential benefits of intravenous transplantation of OECs in a rat hemisection SCI model. OECs derived from olfactory bulb tissue were labeled with quantum dots (QDs), and their biodistribution after intravenous transplantation was tracked using a fluorescence imaging system. Accumulation of the transplanted OECs was observed in the injured spinal cord within 10 min, peaked at seven days after cell transplantation, and decreased gradually thereafter. This time window corresponded to the blood-spinal cord barrier (BSCB) opening time, which was quantitated with the Evans blue leakage assay. Using immunohistochemistry, we examined neuronal growth (GAP-43), remyelination (MBP), and microglia (Iba-1) reactions at the lesion site. Motor function recovery was also measured using a classic open field test (Basso, Beattie and Bresnahan score). Compared with the group injected only with QDs, the rats that received OEC transplantation exhibited a prominent reduction in inflammatory responses, increased neurogenesis and remyelination, and significant improvement in motor function. We suggest that intravenous injection could also be an effective method for delivering OECs and improving functional outcomes after SCI. Moreover, the time course of BSCB disruption provides a clinically relevant therapeutic window for cell-based intervention.


Get the story straight: contextual repetition promotes word learning from storybooks.
Although shared storybook reading is a common activity believed to improve the language skills of preschool children, how children learn new vocabulary from such experiences has been largely neglected in the literature. The current study systematically explores the effects of repeatedly reading the same storybooks on both young children's fast and slow mapping abilities. Specially created storybooks were read to 3-year-old children three times during the course of 1 week. Each of the nine storybooks contained two novel name-object pairs. At each session, children either heard three different stories with the same two novel name-object pairs or the same story three times. Importantly, all children heard each novel name the same number of times. Both immediate recall and retention were tested with a four-alternative forced-choice task with pictures of the novel objects. Children who heard the same stories repeatedly were very accurate on both the immediate recall and retention tasks. In contrast, children who heard different stories were only accurate on immediate recall during the last two sessions and failed to learn any of the new words. Overall, then, we found a dramatic increase in children's ability to both recall and retain novel name-object associations encountered during shared storybook reading when they heard the same stories multiple times in succession. Results are discussed in terms of contextual cueing effects observed in other cognitive domains.


Differentiation between single bladder cancer cells using principal component analysis of time-of-flight secondary ion mass spectrometry.
Time-of-flight-secondary ion mass spectrometry (TOF-SIMS) mass spectra measurements combined with an appropriate sample preparation protocol are the powerful tools to obtain unique information about the chemical composition of biological materials. In our studies, two questions were addressed, i.e., whether it is possible to develop a fixative-based sample preparation protocol and whether it allows one to distinguish between cells originating from various stages of cancer progression. Therefore, four human bladder cancer cell lines (with distinct malignancy degree) have been investigated. A chemical fixation protocol has been used for TOF-SIMS measurements, and mass spectra were obtained using a Bi3(+) primary ion beam. The principal component analysis (PCA) has been applied to analyze the whole range of mass spectra (without preselection of any particular masses) using two approaches of data preprocessing, namely, mean centering and autoscaling. The PC3 versus PC2 plot has showed significant differences between nonmalignant cancer cells and the cancerous ones for both of preprocessing approaches. The analysis of mass spectra of human bladder cells allows one to find a list of mass peaks with intensities significantly larger in cancerous bladder cells compared to nonmalignant cell cancer of the ureter (HCV29 cells). These findings show that TOF-SIMS in combination with PCA can be used to identify reference, human bladder cells from cancerous ones.