Broxaterol: a double-blind clinical trial comparing broxaterol and salbutamol.
10 patients with reversible bronchospasm received by the oral route in a double-blind fashion broxaterol, Z. 1170, 0.250 and 0.500 mg in comparison with salbutamol 4 mg as base and a placebo. Measurements of FEV1, heart rate and arterial pressure were performed before and 0.5, 1, 2, 4, 6 h after each treatment. Z. 1170 was followed by increases in FEV1 over the baseline and the placebo values that were significant up to the 4th hour with the 0.500 mg dose, up to the 2nd hour with the 0.250 mg dose. The difference between the effects of the two dose levels of Z. 1170 was significant, and the effect of the 0.500 mg dose was not significantly different from that of salbutamol 4 mg. The maximum increments in FEV1 following Z. 1170 averaged 15.8% for the 0.250 mg dose, 24.3% for 0.500 mg dose, and they were recorded at the 2nd hour. At this time point the mean increment in FEV1 following salbutamol was 18.0%. The maximum increments in FEV1 with salbutamol averaged 18.7% and were recorded at the 1st hour. At this time the mean increments for Z. 1170 0.250 and 0.500 mg were 13.8 and 20.0%, respectively. Heart rate and arterial pressure did not show any changes of clinical significance.


Catheterization of Pulmonary and Carotid Arteries for Concurrent Measurement of Mean Pulmonary and Systemic Arterial Pressure in Rat Models of Pulmonary Arterial Hypertension.
Pulmonary hypertension (PH) is a group of pulmonary vascular disorders in which mean pulmonary arterial pressure (mPAP) becomes abnormally high because of various pathological conditions, including remodeling of the pulmonary arteries, lung and heart disorders, or congenital conditions. Various animal models, including mouse and rat models, have been used to recapitulate elevated mPAP observed in PH patients. However, the measurement and recording of mPAP and mean systemic arterial pressure (mSAP) in small animals require microsurgical procedures and a sophisticated data acquisition system. In this paper, we describe the surgical procedures for right heart catheterizations (RHC) to measure mPAP in rats. We also explain the catheterization of the carotid artery for simultaneous measurement of mPAP and mSAP using the PowerLab Data Acquisition system. We enumerate the surgical steps involved in exposing the jugular vein and the carotid artery for catheterizing these two blood vessels. We list the tools used for microsurgery in rats, describe the methods for preparing catheters, and illustrate the process for inserting the catheters in the pulmonary and carotid arteries. Finally, we delineate the steps involved in the calibration and setup of the PowerLab system for recording both mPAP and mSAP. This is the first protocol wherein we meticulously explain the surgical procedures for RHC in rats and the recording of mPAP and mSAP. We believe this protocol will be essential for PH research. Investigators with little training in animal handling can reproduce this microsurgical procedure for RHC in rats and measure mPAP and mSAP in rat models of PH. Further, this protocol is likely to help master RHC in rats that are performed for other conditions, such as heart failure, congenital heart disease, heart valve disorders, and heart transplantation.


A Systematic Review of Systematic Reviews on the COVID-19 Pandemic.
COVID-19 a systemic inflammation involving multiple organs, affecting all age groups, with high mortality rate, severe adverse outcomes, and high economic burden need to be described. A systematic review of systematic reviews conducted. We searched PubMed, OVID Medline, Cochrane library, COVID-19 resource centers of N Engl. J Med, AHA, and LITCOVID. Certainty of evidences was evaluated by GRADE approach. Meta-analysis according to random effects model was conducted. Seventy-one eligible systematic reviews are included in the study. A total of 86.5% of them had high quality, and 13.5% had medium quality. Meta-analysis results are presented in tabular format, and the remaining results are presented in narration fashion. COVID-19 involves blood vessels, lung, heart, nervous system, liver, gastrointestinal system, kidney, eyes, and other organs and infects adult and children, neonates, pregnant women, and elderly, transmitted via air born and droplet. Comorbidities associated with COVID-19 are HTN 20.7%, CVD 9.6%, DM 9.55%, respiratory diseases 7%, and 9% of cigarette smoking. Prognostic factors for mortality among COVID-19 cases are acute cardiac injury, diagnosed CVD, DM, respiratory disease, and HTN. Prognostic factors for disease severity are CVD and HTN. Prognostic factors for disease progression were fever, shortness of breath, and smoking. There is no specific antiviral treatment. Preventive measures including physical distancing of 2 m and more, using PPE, avoiding social gatherings, quarantine, and isolation have been recommended. Encouraging telemedicine, online training, and homeschooling are highly recommended. Vaccine is approaching, and concerns exist about vaccine with a high efficacy. Modification of CVD and cardiometabolic risk became the cornerstone for sustainable control of pandemic.


[A case of suspected pulmonary thrombosis in a patient with reactive thrombocytemia who underwent liver subsegmentectomy].
A 68-year-old man with reactive thrombocytemia (platelet count: 97.2 x 10(4).mm-3) underwent liver subsegmentectomy for hepatocellular carcinoma. Thoracic epidural combined with general anesthesia was carried out for the surgery. Platelet aggregability was monitored during the operation. At the beginning of the operation, platelet aggregability to aggregating factor ADP showed an abnormal pattern without dose dependency. In spite of continuous administration of gabexate mesilate for inhibition of thrombosis, the patient developed hypercapnia with low end tidal CO2 pressure (PETCO2) and hypoxia, suggesting pulmonary embolism. PETCO2 and SPO2 recovered soon after heparin administration. The patient recovered without any neurologic complications. This case demonstrated that hyperaggregability is possible in patients with thrombocytemia and suggests that monitoring of platelet function in patients with thrombocytemia is difficult.


Effects of substitutive therapy on right ventricular systolic and diastolic functions in patients with idiopathic hypogonadotropic hypogonadism.
There have been controversial studies evaluating ventricular functions in patients with idiopathic hypogonadotropic hypogonadism (IHH). A recent study has demonstrated that low serum testosterone levels are associated with increased cardiovascular mortality. We aimed to investigate ventricular functions by standard echocardiography and examine the effects of substitutive therapy on right ventricular (RV) functions in patients with IHH by means of pulsed wave tissue Doppler imaging (PWTDI). Twenty-three patients with IHH and 31 controls were evaluated by standard echocardiography and PWTDI. Isovolumic acceleration (IVA), myocardial systolic wave (Sm) velocity, myocardial precontraction time (PCTm), and PCTm to contraction time (CTm) ratio were determined as systolic indices. Myocardial relaxation time (RTm), early (Em) velocity, late (Am) velocity, and Em to Am ratio were determined as diastolic indices. Peak pulmonary artery pressure (PAP) was significantly higher in control subjects (p=0.008). IVA and Sm values were similar in patients and controls. Em, Am velocities, and their ratios did not differ. PCTm was significantly longer (p=0.001) and PCTm to CTm ratio was significantly higher in patients (p=0.001). These parameters also decreased after replacement therapy, albeit not statistically significantly (p>0.05). PAP was significantly higher after substitutive therapy (p=0.009). Ventricular functions are normal in patients with IHH. Substitutive therapy has no effects on RV functions. However, substitutive therapy may increase PAP in small amounts, which has no immediate clinical implication with short-term use.


Adsorption Behaviors of L-Histidine and DL-Tryptophan on Cholesterol, Silica, Alumina, and Graphite.
The adsorption of L-histidine (L-His) and DL-tryptophan (DL-Trp) on cholesterol, silica, alumina, and graphite surfaces from aqueous solution at pH 9.2 has been studied in the temperature range of 25 to 50 degrees C. The data have been analyzed, wherever applicable, by Langmuir and Hill equations to obtain (1) the monolayer adsorption capacity (x(m)) and the equilibrium constant (k') for the adsorption and desorption processes and (2) the Hill coefficient (n) at different temperatures. The results of adsorption on different kinds of adsorbents have been compared. The energetic parameters for the adsorption process have also been evaluated and compared. Copyright 2001 Academic Press.


Reptile adenoviruses in cattle?
This paper describes a hypothesis on the origin of the members of the recently established adenovirus genus, Atadenovirus, invading cattle, sheep, deer, duck and poultry. Comparison of the phylogenetic trees of adenoviruses and their hosts suggests a very ancient but common origin for the atadenoviruses. The surprisingly large difference between these virus types and other adenoviruses infecting the same host can be easily understood by assuming their separate evolution in different hosts (e.g., in reptiles versus a coevolution with mammals and birds, respectively) followed by a later host switch.


Differential relationship of observer-rated and self-rated depression and anxiety scales with heart rate variability features.
Heart rate variability (HRV) is a known psychophysiological marker for diverse psychiatric symptoms. In this study, we aimed to explore the potential for clinical use of HRV by investigating the interrelationship between HRV indices and clinical measures mainly used to assess depressive and anxious symptoms. Participants who reported depressive and anxious symptoms were designated into the following groups: group 1, clinician-rated and self-rated depression; group 2, only self-rated depression; group 3, clinician-rated and self-rated anxiety; group 4, only self-rated anxiety. Statistical comparisons were performed between these groups to investigate the association between HRV and clinical measures. As a result, HRV variables showed significant correlations only with the clinician-rated assessments. Moreover, both time and frequency domain HRV indices were significantly different between groups 1 and 2, but groups 3 and 4 showed significant differences only in frequency domain HRV indices. Our study showed that HRV is an objective indicator for depressive or anxious symptoms. Additionally, it is considered a potential indicator for predicting the severity or state of depressive symptoms rather than of anxious symptoms. This study will contribute to increasing the diagnostic utility of discriminating those symptoms based on HRV in the future.


Phenotypic Assay Leads to Discovery of Mitophagy Inducers with Therapeutic Potential for Parkinson's Disease.
Mitophagy, the selective degradation of mitochondria by autophagy, involved in important physiological processes and defects in pathways has been reported in pathological conditions, such as neurodegeneration. Thus, mitophagy is an interesting target for drug discovery programs. In this investigation, we used robust phenotypic assay to screen a set of 50 small heterocyclic compounds to identify inducers of mitophagy. We identified two compounds, VP07 and JAR1.39, that induce Parkin-dependent mitophagy. Based on structure-activity relationship studies, we proposed the ability of the compounds to act as light chain 3 (LC3) interactors, similar to cardiolipin or ceramide, triggering mitophagy via Pink1/Parkin. Finally, we show promising therapeutic applicability in a cellular model of Parkinson's disease.


[THE SELF-ASSESSMENT OF PHYSICIANS THEIR QUALIFICATION AND SOCIAL STATUS].
The 103 medical organizations of the Tverskaia oblast were involved as study base to carry out questionnaire survey of physicians of different specialties concerning issues of self-assessment of qualification and social status. The most of the respondents (66.8 ± 1.98%) assessed themselves as good specialists, 20.8 ± 1.71% as fair specialists and 11.9 ± 1.36%--as perfect specialists. The own social status respondents assessed in general as not too high. So, 53.1 ± 2.10% of physicians refer themselves to middle class of society and 30 ± 1.93%--to below middle class of society. Among respondents, 3 ± 0.71% referred themselves to high class of society and 3.2 ± 0.74%--to the lowest class of society. The low incomes and overwork were noted by respondents as main problems of their life. The study results testify the necessity of correction of programs of medical education at all levels, actuality of activities of increasing social status of physician and development of benevolent conditions of work and rest.


Pulmonary Function of Young Muslim Males During the Month of Ramadan.
During the month of Ramadan intermittent fasting (RIF), both dietary and sleep patterns are adversely affected to cope with the rituals of Ramadan. Literature suggests that sleep deprivation and alteration of dietary pattern and nutritional impairment affect the pulmonary structure and function. Pulmonary function during RIF was not explored earlier. The present study aimed to investigate the effects of RIF on pulmonary function tests (PFTs) in healthy young Muslim males. Fifty sedentary nonsmoking healthy young Muslim male individuals of 20 to 25 years of age without any history of pulmonary or other major diseases were recruited by simple random sampling from different parts of Kolkata, India. Participants completed the American Thoracic Society questionnaire to record their personal demographic data, health status, and consent to participate in the study. Expirograph and peak flow meter were used to record the pulmonary function parameters (PFTs). PFTs were within the normal range and did not show any significant variation during the RIF. Body height and body mass depicted significant correlation ( p < .05, p < .001) with PFTs. Tidal volume, vital capacity, and peak expiratory flow rate had significant correlation ( p < .05, p < .01, p < .001) with age. Simple and multiple regression equations were computed to predict PFTs in the studies population. RIF did not affect the normal range of PFTs in young Muslim males of Kolkata, India. Standard errors of estimate of the computed regression equations were substantially small enough to recommend these equations as norms to predict the PFTs in the studied population.


Important players in carcinogenesis as potential targets in cancer therapy: an update.
The development of cancer is a problem that has accompanied mankind for years. The growing number of cases, emerging drug resistance, and the need to reduce the serious side effects of pharmacotherapy are forcing scientists to better understand the complex mechanisms responsible for the initiation, promotion, and progression of the disease. This paper discusses the modulation of the particular stages of carcinogenesis by selected physiological factors, including: acetylcholine (ACh), peroxisome proliferator-activated receptors (PPAR), fatty acid-binding proteins (FABPs), Bruton's tyrosine kinase (Btk), aquaporins (AQPs), insulin-like growth factor-2 (IGF-2), and exosomes. Understanding their role may contribute to the development of more effective and safer therapies based on new binding sites.


Resolution of tinea pedis with imiquimod cream 5% in a patient with nodular basal cell carcinoma.
A 73-year-old white man with nodular basal cell carcinoma (nBCC) of the toe and interdigital tinea pedis was treated with imiquimod cream 5% once daily for 4 weeks and twice daily for 10 weeks. Results of a posttreatment potassium hydroxide (KOH) preparation and biopsy confirmed clearance of both tinea pedis and nBCC, respectively.


Crystal structure of an acidic phospholipase A2 from the venom of Agkistrodon halys pallas at 2.0 A resolution.
The crystal structure of acidic phospholipase A2 from the venom of Agkistrodon halys pallas has been determined by molecular replacement at 2.0 A resolution to a crystallographic R-factor of 0.157. The overall structure of the molecule is very similar to those of other phospholipase A2 species of known structure. The catalytic site, the hydrophobic channel and the N-terminal region show greatest structural conservation. The Ca(2+)-binding region has a conformation that resembles closely that of bovine PLA2 rather than Crotalus atrox PLA2. Compared with other PLA2 species, the conformation of the C-terminal ridge shows significant difference due to the insertion of two residues. A unique aromatic patch appears on one face of the molecules, surrounded by two acidic residues, the relevant features of this structure and their possible biological implications are discussed.


Noise-induced hearing loss among U.S. Air Force cryptolinguists.
Occupational noise-induced hearing loss remains epidemic in the U.S. Air Force (USAF) and aircrew members continue to be affected. This study examines noise-induced hearing loss (NIHL) observed among USAF cryptolinguists that is attributable to radio noise and attempts to determine whether the current USAF Hearing Conservation Program (HCP) adequately identifies NIHL. Audiograms from 120 ground-based cryptolinguists were examined. Comparisons were made between 1998 audiograms and either the reference audiogram or the enlistment audiogram. To determine HCP effectiveness, results were compared with the USAF standard of 3% or fewer permanent threshold shifts (PTS) per year. Some 13.3% of the cryptolinguists experienced standard threshold shifts (STS) between their enlistment audiogram and their initial occupational (reference) audiogram; 9.2% experienced STS in 1998 as compared with their initial enlistment audiogram but only 6 of the 11 (54%) were detectable using the reference audiogram as the baseline. The frequency pattern of changes in hearing thresholds was characteristic for NIHL. The NIHL that occurs among cryptolinguists prior to performance of the reference audiogram, and the hearing threshold shifts that occur between the enlistment audiogram and the reference audiogram, may obscure future hearing loss in the population. The incidence of PTS appeared to exceed 3% when the enlistment audiogram was used. While this result was not significantly different from 3%, sample size limitations and data accuracy concerns warrant that this population be closely watched in the future.


[Mitochondrial DNA copy number of leucocytes as ageing marker and risk factors for age-related diseases in human.]
We used quantitative real-time PCR method to analyse mtDNA copy number in a random subsample (n=996; 358 men aged 66,31±7,24 years; 468 women aged 67,62±7,1 years) selected from a population cohort (n=9 630) examined at baseline in international project HAPIEE in Novosibirsk, Russia, in 2003-2005. The participants were re-examined after 12 years in 2015-2017. The average relative number of mtDNA copies in peripheral blood leukocytes was greater in women than in men, independently of age and smoking (p=0,001). mtDNA copy number was inversely correlated with age both in men (p=0,005) and women (p<0,001). In age adjusted analysis, mtDNA copy number was inversely associated with waist, hip and heart rate in both sexes. In addition, mtDNA copy number in women was inversely associated with triglycerides and glucose, aterogenity index and positively with HDL cholesterol. In men, mtDNA copy number was positively associated with physical activity. The age-adjusted mean of mtDNA copy number among male never-smokers was greater than in smokers (p=0,003), and the mean mtDNA copy number was lower in women with diabetes than in women without diabetes (p=0,005). In both sexes, subjects with baseline history of hypertension had lower mtDNA copy number after 12-year follow-up than those without hypertension (p=0,05). This broadly supports the hypothesis that mtDNA copy number may act as biomarker of ageing.


Dependence on material choice of degradation of organic solar cells following exposure to humid air.
Electron microscopy has been used to study the degradation of organic solar cells when exposed to humid air. Devices with various different combinations of commonly used organic solar cell hole transport layers and cathode materials have been investigated. In this way the ingress of water and the effect it has on devices could be studied. It was found that calcium and aluminum in the cathode both react with water, causing voids and delamination within the device. The use of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) was found to increase the degradation by easing water ingress into the device. Replacing these materials removed these degradation features. © 2015 The Authors. Journal of Polymer Science Part B: Polymer Physics published by Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 216-224.


Hydrogen peroxide removal with magnetically responsive Saccharomyces cerevisiae cells.
Hydrogen peroxide (HP) is a promising chemical sanitizer for use in the food industry. Its residues have to be decomposed, usually using an enzyme process employing catalase. In order to offer an inexpensive biocatalyst and to simplify subsequent manipulation, we have prepared magnetically responsive alginate beads containing entrapped Saccharomyces cerevisiae cells and magnetite microparticles. Larger beads (2-3 mm in diameter) were prepared by dropping the mixture into calcium chloride solution, while microbeads (the diameter of majority of particles ranged between 50 and 100 microm) were prepared using the water in oil emulsification process. In general, microbeads enabled more efficient HP decomposition. The prepared microparticulate biocatalyst caused efficient decomposition of HP in water solutions (up to 2% concentration), leaving very low residual HP concentration after treatment (below 0.001% under appropriate conditions). The biocatalyst was stable; the same catalytic activity was observed after one month storage at 4 degrees C, and the microbeads could be used at least five times.


[The medical sociological analysis of the factors affecting the mortality with taking into consideration the gender and age differences].
The issue of various factors affecting the mortality rate of population in the light of the gender and age differences is considered. The medical demographic and medical sociological statistical data of mortality is presented in its ontogenesis and is differentiated according time periods. The issue of death-rate among the mentally ill patients depending on their gender characteristics is discussed. The focal point in the article is the evaluation of association between the age of parents and the longevity of posterity. The data revealing the relationship between mother's age and the risk of mental disease development is provided.


Confirming the species-sensitivity distribution concept for endosulfan using laboratory, mesocosm, and field data.
In Australia, water-quality trigger values for toxicants are derived using protective concentration values based on species-sensitivity distribution (SSD) curves. SSD curves are generally derived from laboratory data with an emphasis on using local or site-specific data. In this study, Australian and non-Australian laboratory-species based SSD curves were compared and the concept of species protection confirmed by comparison of laboratory-based SSD curves with local mesocosm experiments and field monitoring data. Acute LC50 data for the organochlorine pesticide endosulfan were used for these comparisons; SSD curves were fitted using the Burr type III distribution. SSD curves indicated that the sensitivities of Australian fish and arthropods were not significantly different from those of corresponding non-Australian taxa. Arthropod taxa in the mesocosm were less sensitive than taxa in laboratory tests, which suggests that laboratory-generated single-species data may be used to predict concentrations protective of semifield (mesocosm) systems. SSDs based on laboratory data were also protective of field populations.


Pre-resonance-stimulated Raman scattering for water bilayer structure on laser-induced plasma bubble surface.
Pre-resonance-stimulated Raman scattering (PSRS) from water molecules in the air/water interfacial regions was studied when the laser-induced plasma bubble was generated at the interfaces. A characteristically lower Raman shift of OH-stretching vibrational modes of water molecules at around 3000 cm(-1) (370 meV) was observed, in which the mechanisms were possibly attributed to the strong hydrogen bond in a well-ordered water bilayer structure that was formed on a laser-induced plasma bubble surface. Simultaneously, the PSRS of ice Ih at about 3100 cm(-1) was obtained, which also belonged to the strong hydrogen bond effect in ice Ih structure.


Refractive index of soybean leaf cell walls.
The refractive index of soybean (Glycine max [L.] Merr.) leaf cell walls was measured by two methods. The refractive index of fully hydrated walls in the living leaf was about 1.415, while that of dried cell walls was about 1.53. The refractive index of the external surface of the living leaf hair was 1.48.


Cultural changes in ICU sedation management.
The aim of this study was to explore physicians' views and perceptions of sedation, and offer a new approach to the understanding of issues of sedation. I used a qualitative, descriptive, and explorative multicenter design. Data were generated by seven key-informant interviews using a semistructured interview guide. One experienced doctor was selected at each of the seven largest intensive care units in Denmark. Interpretational analysis was performed by comprehensive overview, individual case analysis, cross-case analysis, and integrated thematic analysis and identification of emerging themes. The following themes emerged: a paradigm shift from sedated to more awake and comfortable patients, cultural changes toward intracollegial openness, increased interdisciplinary and staff/patient/family collaboration, patient and environmental normalization, and humanization. The study findings provide an understanding of contextual issues of sedation, safety, and comfort, and suggest that a cultural change in sedation strategies might reduce the duration of sedation and mechanical ventilation while containing cost and improving the well-being of the patients.


[Enteroinsular hormones in chronic gastritis with secretory insufficiency].
The blood serum content of secretin, vasointestinal peptide (VIP), glucagon and insulin was studied in 112 patients with chronic gastritis presenting with secretory deficiency, and 12 essentially healthy subjects. It was established that in surface, fundal and pangastritis the levels of secretin and VIP did not differ from the values in healthy individuals. The secretin concentration tended to be the lowest in atrophic fundal and atrophic pangastritis. They also had significantly elevated concentrations of VIP and glucagon, with insulin decreased. Caused by different exo- and endogenous factors phenomena characteristic of gastritis, such as disturbances in acid-producing function of the stomach, to mention but one of its manifestations, result in changes of stimulatory effects of acidification on enterinic elements of the small intestine, which circumstance leads to discoordination in output of intestinal and pancreatic hormones particularly pronounced in atrophic gastritis.


7 habits of highly effective.
There is a pressing need for psychiatric nurse authors to write about their professional image as well as issues they face in clinical practice. In this article, two psychiatric nurses describe how using Covey's The 7 Habits of Highly Effective People: Powerful Lessons in Personal Change can serve as a framework for increasing writing productivity. In addition, the Myers-Briggs Type Indicator can increase awareness of and appreciation for the strengths and differences in each author's writing style. Using these tools, writing can become a process of discovery.


Curare-induced transformation of myosin pattern in developing skeletal muscle fibers.
The effects of neuromuscular block on the pattern of distribution of myosin isozymes in developing skeletal muscle fibers was examined by immunocytochemistry. The homogeneous population of fibers in the anterior latissimus dorsi (ALD) of the 18-day chick embryo was converted by curare to a mosaic of at least two categories of fibers. Normally all fibers in this slow muscle reacted with antibodies against slow myosin (anti-ALD). They also reacted with an antibody specific for the alkali 1 light chain (anti-delta 1) but not the alkali 2 light chain (anti-delta 2) of fast myosin. After treatment with curare, which inhibits neuronal cell death and increases the number of axonal endings, ALD muscle fibers continued to react with anti-delta 1, but many now reacted with anti-delta 2 as well. The same fibers failed to react with anti-ALD. From this it can be concluded that the myosin in this population was converted to a type not normally present. The changes, therefore, are not merely a result of the preferential loss of a slow type of fiber, nor are they a result of delayed maturation. In contrast, curare had no apparent effect on the fast posterior latissimus dorsi (PLD). As in the normal muscle at 18 days, all fibers reacted strongly with anti-delta 1 and to variable degrees with anti-delta 2, and very few fibers reacted with anti-ALD. Our observations suggest that the dual response to antibodies against fast and slow myosin during development is not a necessary consequence of multiple axon terminals. We present evidence that curare induces the expression of a different myosin in the embryonic ALD, and we suggest that the selective transformation of the fiber population may be a manifestation of a change in composition of the motoneuron pool.


[The morphologic and functional state of the kidneys exposed to focused waves during remote nephro-lithotripsy].
Clinical and experimental research has shown that complications connected with negative influence of focused waves in distant lithotripsy in litotripters with an electrohydravlic system of focused waves generation depend on many factors, including the regime of wave generator work, an electrode interval, defocusing the wave as a result of an electrode interval center displacement, the amplitude of pressure and the length of a wave impulse in positive and negative phases. The wave impulse is distorted, which leads to kidney tissue damage.


Gas detection by structural variations of fluorescent guest molecules in a flexible porous coordination polymer.
The development of a new methodology for visualizing and detecting gases is imperative for various applications. Here, we report a novel strategy in which gas molecules are detected by signals from a reporter guest that can read out a host structural transformation. A composite between a flexible porous coordination polymer and fluorescent reporter distyrylbenzene (DSB) selectively adsorbed CO₂ over other atmospheric gases. This adsorption induced a host transformation, which was accompanied by conformational variations of the included DSB. This read-out process resulted in a critical change in DSB fluorescence at a specific threshold pressure. The composite shows different fluorescence responses to CO₂ and acetylene, compounds that have similar physicochemical properties. Our system showed, for the first time, that fluorescent molecules can detect gases without any chemical interaction or energy transfer. The host-guest coupled transformations play a pivotal role in converting the gas adsorption events into detectable output signals.


Women with posterior tibial tendon dysfunction have diminished ankle and hip muscle performance.
Controlled laboratory study using a cross-sectional design. To characterize ankle and hip muscle performance in women with posterior tibial tendon dysfunction (PTTD) and compare them to matched controls. We hypothesized that ankle plantar flexor strength, and hip extensor and abductor strength and endurance, would be diminished in women with PTTD and this impairment would be on the side of dysfunction. Individuals with PTTD demonstrate impaired walking abilities. Walking gait is strongly dependent on the performance of calf and hip musculature. Thirty-four middle-aged women (17 with PTTD) participated. Ankle plantar flexor strength was assessed with the single-leg heel raise test. Hip muscle performance, including strength and endurance, were dynamometrically measured. Differences between groups and sides were assessed with a mixed-model analysis of variance. Females with PTTD performed significantly fewer single-leg heel raises and repeated sagittal and frontal plane non-weight-bearing leg lifts, and also had lower hip extensor and abductor torques than age-matched controls. There were no differences between sides for hip strength and endurance measures for either group, but differences between sides in ankle strength measures were noted in both groups. Women with PTTD demonstrated decreased ankle and hip muscle performance bilaterally.


The tomato xylem sap protein XSP10 is required for full susceptibility to Fusarium wilt disease.
XSP10 is an abundant 10 kDa protein found in the xylem sap of tomato. The protein displays structural similarity to plant lipid transfer proteins (LTPs). LTPs are involved in various physiological processes, including disease resistance, and some are able to bind and transfer diverse lipid molecules. XSP10 abundance in xylem sap declines upon infection with Fusarium oxysporum f. sp. lycopersici (Fol), implying involvement of XSP10 in the plant-pathogen interaction. Here, the biochemical characterization of XSP10 with respect to fatty acid-binding properties is reported; a weak but significant binding to saturated fatty acids was found. Furthermore, XSP10-silenced tomato plants were engineered and it was found that these plants exhibited reduced disease symptom development upon infection with a virulent strain of Fol. Interestingly, the reduced symptoms observed did not correlate with an altered expression profile for known reporter genes of plant defence (PR-1 and WIPI). This work demonstrates that XSP10 has lipid-binding properties and is required for full susceptibility of tomato to Fusarium wilt.


Development of a biomarker to monitor target engagement after treatment with dihydroorotate dehydrogenase inhibitors.
Dihydroorotate dehydrogenase (DHODH) catalyzes a key step in pyrimidine biosynthesis and has recently been validated as a therapeutic target for malaria through clinical studies on the triazolopyrimidine-based Plasmodium DHODH inhibitor DSM265. Selective toxicity towards Plasmodium species could be achieved because malaria parasites lack pyrimidine salvage pathways, and DSM265 selectively inhibits Plasmodium DHODH over the human enzyme. However, while DSM265 does not inhibit human DHODH, it inhibits DHODH from several preclinical species, including mice, suggesting that toxicity could result from on-target DHODH inhibition in those species. We describe here the use of dihydroorotate (DHO) as a biomarker of DHODH inhibition. Treatment of mammalian cells with DSM265 or the mammalian DHODH inhibitor teriflunomide led to increases in DHO where the extent of biomarker buildup correlated with both dose and inhibitor potency on DHODH. Treatment of mice with leflunomide (teriflunomide prodrug) caused a large dose-dependent buildup of DHO in blood (up to 16-fold) and urine (up to 5,400-fold) that was not observed for mice treated with DSM265. Unbound plasma teriflunomide levels reached 20-85-fold above the mouse DHODH IC50, while free DSM265 levels were only 1.6-4.2-fold above, barely achieving ∼ IC90 concentrations, suggesting that unbound DSM265 plasma levels are not sufficient to block the pathway in vivo. Thus, any toxicity associated with DSM265 treatment in mice is likely caused by off-target mechanisms. The identification of a robust biomarker for mammalian DHODH inhibition represents an important advance to generally monitor for on-target effects in preclinical and clinical applications of DHODH inhibitors used to treat human disease.


Gas composition of the human nose and nasopharyngeal space.
Since it was established that middle ear (ME) gas composition is closer to venous gas composition than to air, the question arose regarding the composition of gas which enters the ME from the nasopharynx. Using a mass spectrometer, gaseous partial pressure was measured at three locations in the nose and nasopharynx of 6 volunteers. All three locations showed similar gas composition (O2 = 15.7%, CO2 = 4.5%, N2 + Ar = 79.8%) which is similar to expired air. The gas that enters the ME via the Eustachian tube is a mixture closer to the final ME gas equilibrium than is air. This minimizes the changes in steady state ME gas composition incurred by gas influx into the ME.


Hydrogen-Bonding-Driven Ion-Pair Formation in Protic Ionic Liquid Aqueous Solution.
Protic ionic liquids (PILs) in solution especially in water have attracted more and more attention due to their unique properties. The solvation of PILs in water is important to their properties and applications. To explore the solvation of bio-based PILs in water, acidity of 49 [AA]X amino acid ionic liquids (AAILs) consisting of 7 different cations and 7 different anions was studied as a favorable probe. The pKa values for [AA]X PILs containing same cations were obtained and discussed. The acidity strength of the [AA]X PILs varies with both cation and anion which does not follow the conventional assumption that the acidity for PILs is independent of anions. The acidic discrepancy of [AA]X PILs aqueous solution is probably mediated by the formation of ion pairs according to a revised solvation model of PILs. Quantum-chemistry calculation was employed to unpuzzle anion's different effects on the acid balance of cations where cation-anion hydrogen bonds play an important role. Such difference in acidity allows us to understand the formation of solvated ion pairs. This work provides an insight into the fundamental solvation of PILs from acid perspective and their influence on acidity properties for the first time.


Increment of the extinction illusion by long stimulation.
We quantitatively examined the effect of stimulus duration on the extinction illusion. A white disc was presented or not presented at an intersection of a grey grid (intersection configuration) or on a homogeneous background (background configuration). The extinction illusion was quantified as the subtraction of no-disc responses in the background configuration (ie baseline) from no-disc responses in the intersection configuration, when the disc was presented. Experiment 1 showed a temporal effect: the extinction illusion increased as stimulus duration increased; this temporal effect was observed when the disc was presented at 9 deg from the fixation point and when the stimulus duration was 1000-6000 ms. Experiment 2 showed a visual field anisotropy: the extinction illusion occurred more frequently in the upper visual field than in the lower visual field, when the stimulus duration was 200 ms; the anisotropy was not observed when the stimulus duration was 6000 ms. Experiment 3 showed an alley-length effect: when the grid alley was long, the extinction illusion occurred more frequently in the 6000 ms condition than in the 200 ms condition; the temporal effect was not observed when the grid alley was short. These results suggest that the temporal effect of the extinction illusion might be due to perceptual filling-in of luminance information of the grid alley.


Hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons: histochemical relationship to thyrotropin-releasing hormone, melanin-concentrating hormone, orexin/hypocretin and neuropeptide Y.
Recent demonstrations of the feeding-inhibitory properties of putative peptides derived from cocaine- and amphetamine-regulated transcript (CART) raise the question of interactions between CART peptides and other messenger molecules implicated in the control of food intake. The present study investigated the histochemical relationship of CART to the neuropeptides thyrotropin-releasing hormone (TRH), melanin-concentrating hormone (MCH), orexin/hypocretin and neuropeptide Y (NPY) in the hypothalamus. Double-label in situ hybridization showed that CART to a great extent is co-expressed with TRH in hypothalamic paraventricular nucleus neurons. This technique was also used to demonstrate that MCH, but not orexin/hypocretin, mRNA colocalized with CART in neurons of the dorsomedial hypothalamic nucleus/lateral hypothalamic area. CART-peptide immunoreactive cell bodies in this region, as well as in the arcuate nucleus and the medial posterodorsal nucleus of the amygdala, were all seen to have close appositions formed by NPY-immunoreactive nerve terminals. Lastly, in a study of mice treated with the neurotoxin, monosodium glutamate, which targets the arcuate nucleus, a near-total ablation of CART peptide immunoreactive cell bodies in this nucleus was accompanied by decreased terminal staining for CART peptide in the paraventricular hypothalamic nucleus, the arcuate nucleus itself and in the dorsomedial hypothalamic nucleus. These findings further define the position of hypothalamic CART neurons within the hierarchy of brain circuitries regulating energy balance, demonstrating the presence of CART peptide in several cell populations that form putative down-stream targets of NPY terminals, including hypophysiotropic TRH neurons and lateral hypothalamic MCH neurons.


Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors.
Angiotensin-converting enzyme-related carboxypeptidase (ACE2) is a recently identified zinc metalloprotease with carboxypeptidase activity that was identified using our genomics platform. We implemented a rational design approach to identify potent and selective ACE2 inhibitors. To this end, picomolar inhibitors of ACE2 were designed and synthesized.


The effects of Islam and traditional practices on women's health and reproduction.
The aim of this study was to investigate the effects of Islam as a religion and culture on Turkish women's health. The study included 138 household members residing in the territory of three primary health care centers in Turkey: Güzelbahçe, Fahrettin Altay and Esentepe. Data were collected by means of a questionnaire prepared by a multidisciplinary team that included specialists from the departments of public health, psychiatric nursing and sociology. We found that the women's health behavior changed from traditional to rational as education levels increased, and that religious and traditional attitudes and behaviors were predominant in the countryside, especially practices related to pregnancy, delivery, the postpartum period, induced abortion and family planning. One of the most important prerequisites for the improvement of women's health is that nurses should know the religious practices and culture of the society for which they provide care, so that their efforts to protect and improve women's health will be effective.


Estradiol hypersensitivity and mitogen-activated protein kinase expression in long-term estrogen deprived human breast cancer cells in vivo.
Women with breast cancer who have responded to initial hormonal therapy frequently experience additional remissions upon further endocrine manipulation. We postulate that hypersensitivity to estradiol (E2) may serve as a mechanistic explanation for these secondary responses. We previously provided evidence of hypersensitivity using an in vitro breast cancer model system and demonstrated the role of mitogen-activated protein kinase (MAP kinase) in the process of adaptation to long-term estradiol deprivation. In the present study, we wished to demonstrate that hypersensitivity to E2 could occur under more complex in vivo conditions and that MAP kinase activation is enhanced under these circumstances. We used an MCF-7 breast cancer model system involving long-term estradiol deprived (LTED) cells to produce xenografts in nude mice and an E2 clamp method to precisely control sex steroid levels. The E2 clamp was designed to maintain plasma E2 at a series of doubling doses from 1.25 pg/ml to 20.0 pg/ml in oophorectomized nude mice. As evidence of the validity of the clamp method, a uterine weight bioassay revealed an excellent, linear dose-response relationship between the predicted level of plasma E2 and stimulation of uterine weight. As evidence of hypersensitivity, we found that LTED xenograft tumors grew to a greater extent than wild-type in response to E2 concentrations of 1.25 pg/ml (P = 0.003) and 2.5 pg/ml (P = 0.0002). At the 10.0 and 20.0 pg/ml plasma concentrations, the LTED tumors were stimulated to a lesser extent than the wild-type. This pattern of increased growth at lower concentrations and reduced growth vs. the wild-type at higher concentrations mimics closely the pattern seen for LTED cells in vitro. All LTED cell tumors exhibited enhanced activation of MAP kinase ranging from 18 to 25%, and E2 did not increase this further. In contrast, E2 caused a linear increase in the percentage of activated MAP kinase positive cells (P < 0.0001) in wild-type tumors from basal levels of 2.66% to maximal levels of 6.40%. These observations suggest a dynamic interplay whereby activation of MAP kinase renders cells more sensitive to the proliferative effects of E2. The precise mechanisms for this interplay are unknown but, when further understood, could potentially provide insight into approaches to prevent the evolution of tumors to a hormone insensitive state.


First transfemoral percutaneous edge-to-edge repair of the tricuspid valve using the MitraClip system.
While severe tricuspid regurgitation contributes significantly to morbidity and a poor prognosis in heart failure patients, isolated surgical repair of the tricuspid valve is associated with a high mortality, especially in patients with prior surgery. Percutaneous tricuspid valve repair could contribute to the solution of this dilemma. A recently published report demonstrated the feasibility of tricuspid edge-to-edge repair with the MitraClip® system (Abbott Vascular, Santa Clara, CA, USA) using a transjugular route. In a highly symptomatic patient with severe functional tricuspid regurgitation unsuitable for surgery, we aimed to reduce tricuspid regurgitation using a modified deployment technique for the MitraClip system using a femoral access. A 78-year-old male patient with dilated cardiomyopathy was admitted for his fifth episode of acutely decompensated, predominantly right-sided, heart failure in ten months. Echocardiography showed a moderately to severely reduced left ventricular function and severe functional tricuspid regurgitation. Two clips were deployed in the anterior-septal and posterior-septal commissure of the tricuspid valve, resulting in a significant reduction of the effective regurgitant orifice area. The midterm clinical state of the patient improved. In our patient with severe functional tricuspid regurgitation and suitable anatomy, transfemoral percutaneous tricuspid valve repair was technically feasible and safe by using a modified deployment technique of a widely used repair system developed for the mitral valve. The procedure can be performed without technical modification of the device via a transfemoral route and under echocardiographic guidance. However, particular anatomic and technical aspects can compromise an initial procedural success and demand specific considerations in the future.


Two Kunitz-type inhibitors with activity against trypsin and papain from Pithecellobium dumosum seeds: purification, characterization, and activity towards pest insect digestive enzyme.
Two trypsin inhibitors (called PdKI-3.1 and PdKI-3.2) were purified from the seeds of the Pithecellobium dumosum tree. Inhibitors were obtained by TCA precipitation, affinity chromatography on Trypsin-Sepharose and reversed-phase-HPLC. SDS-PAGE analysis with or without reducing agent showed that they are a single polypeptide chain, and MALDI-TOF analysis determined molecular masses of 19696.96 and 19696.36 Da, respectively. The N-terminal sequence of both inhibitors showed strong identity to the Kunitz family trypsin inhibitors. They were stable over a wide pH (2-9) and temperature (37 to 100 degrees C) range. These inhibitors reduced over 84% of trypsin activity with inhibition constant (Ki) of 4.20 x 10(-8) and 2.88 x 10(-8) M, and also moderately inhibited papain activity, a cysteine proteinase. PdKI-3.1 and PdKI-3.2 mainly inhibited digestive enzymes from Plodia interpunctella, Zabrotes subfasciatus and Ceratitis capitata guts. Results show that both inhibitors are members of the Kunitz-inhibitor family and that they affect the digestive enzyme larvae of diverse orders, indicating a potential insect antifeedant.


Association of HIV neutralizing antibody with lower viral load after treatment interruption in a prospective trial (A5170).
We investigated the impact of neutralizing antibodies (NAbs) on CD4 T-cell count and viral load in a cohort of HAART recipients who underwent extended structured treatment interruption. Substudy of NAb in the AIDS Clinical Trials Group 5170 trial. Early plasma samples from 50 volunteers who discontinued HAART were evaluated in a peripheral blood mononuclear cell-based neutralization assay against a panel of four subtype B primary isolates. We found that high-titer (90% inhibitory dose > 500) NAb against two or more isolates was associated with reduced viral load (P = 0.003 at 12-week posttreatment interruption). This effect faded with time, losing significance (P = 0.161) by study conclusion. Participants possessing the highest NAb levels against individual isolates appeared more likely to have lower viral loads with the association gaining significance against the R5-tropic primary isolate US1 (P = 0.005). There was no association between broader neutralization and CD4 T-cell slope over time. The data suggest that high-titer NAb responses at the time of treatment interruption are associated with reduced viral load over time, but not CD4(+) T-cell decline.


Leadership in Zeiten von Corona: Die Perspektive von Pflegenden und Hebammen in einem Universitätsspital.
Leadership in the time of Corona: The perspective of nurses and midwives at a University Hospital - A quality assessment Abstract. Background: The high number of predicted patients arising from the COVID-19 pandemic presents several challenges to hospitals. Data is available on psychological stress in caregivers during pandemics. To date, there are no known studies regarding the impact of leadership on nursing and midwifery practice. Aim: Evaluation of leadership during the COVID-19 pandemic at a Swiss University Hospital. Methods: The approach to this study was based on action research. The authors defined quality indicators and "values of excellence" on the impact of leadership. In May 2020 140 nurses and midwives of different departments were interviewed using one-time questionnaires. The quantitative data was analyzed descriptively and the open questions evaluated by thematic analysis. Results: The results showed that through the combination of different interventions, a mostly positive working situation could be created for the interviewees. Uncertainty existed about the safety measures. The interviewees were highly stressed by their own private situations, the frequent changes in guidelines and the flood of information. However, the staff felt well supported by the leadership teams. Improvements were described in teamwork and decision-making. Conclusions: The results indicate an impact on leadership and demonstrate as well the need for adequate support. The framework of transformational leadership methods, practice development and Lean management empowers the organization to work in a focused manner, effectively and safely during challenging situations.


Prevention of venous thromboembolism in general surgery.
Venous thromboembolism continues to be an important cause of death in hospitalized patients undergoing major elective surgery. A study of autopsy-proven pulmonary embolism in hospital patients showed that venous thromboembolism accounted for 10% of deaths and that recognition of non-fatal thromboembolism continues to be a problem. The incidence of deep vein thrombosis increases with ageing, the annual rate per 1000 being one to three for those aged between 65 and 69 years and from two to eight for those aged between 85 and 89 years. The introduction of low-molecular-weight heparins has resulted in important changes in the management and prophylaxis of venous thromboembolism. Low-molecular-weight heparin preparations reduce the overall incidence of deep vein thrombosis in general surgery by at least 70%. Furthermore, the effect of low-molecular-weight heparin against pulmonary embolism is at least as great as that of low-dose unfractionated heparin. The incidence of serious and minor haemorrhagic events with low-molecular-weight heparin is similar to that with low-dose unfractionated heparin. Prophylaxis is started pre-operatively, and the usual duration for the post-operative period has been 7 days, or until the patient is discharged from the hospital. In conclusion, low-molecular-weight heparin is highly effective in preventing post-operative venous thromboembolism.


Particle size distribution in commercial pig compound feeds in Switzerland: survey and methodological considerations.
The grinding intensity of pig feed is considered one potential predisposing factor for gastric ulcers, and a variety of particle size recommendations have been published for pig feeds. We subjected 51 different commercial compound feeds for pigs (38 meals, 13 pellets/granulates) to dry and/or wet sieve analysis. The amount of particles passing the finest sieve (or being soluble) was estimated by the difference to the total dry matter weighed prior to sieving. Mean particle size was calculated based on the weighted average of the material retained on the sieves (MPSsieves), and additionally with accounting for this lost material (MPStotal). Dry sieve analysis of the meals yielded MPSsieves of 0,58-2,90 mm and MPStotal of 0,58-2,89 mm; only 0,02 to 2,71 % of the dry matter passed all sieves. Wet sieve analysis of all meals and pellets yielded similar MPSsieves of 0,63-1,66 mm, but dramatically lower MPStotal of 0,26-1,04 mm; between 35 and 66 % of the dry matter was not retained on the sieves. Pellets had smaller MPS, and a higher proportion of particles passing all sieves than meals. Depending on the reference used, a maximum of 26 % of meals conformed to recommendations for pig feed particle size. None of the pelleted feeds met these criteria, irrespective of the source consulted for the recommendation. Wet sieving should be considered the standard analysis, because in dry sieving, very fine particles adhering to larger particles may not be registered separately but contribute erroneously to larger particle weight. In addition, the MPS calculation should account for material lost through the finest sieve. Reasons why Swiss pig feed does not meet particle size recommendations should be further investigated.


[Special aspects of diagnosis and therapy of diabetes in liver diseases].
The core of this review are questions dealing with links between diabetes mellitus and liver diseases. Based on the literature and on their own observations the authors conclude that a liver disease may induce and/or worsen the development of type-2 diabetes mellitus (so called hepatogenic diabetes) and vice versa, a diabetes may result in a liver damage, e.g. simple steatosis or even non-alcoholic-steatohepatitis. The diagnosis of diabetes in hepatopathy is defined according to the same criteria as in patients without any hepatic involvement. The treatment is based on adequate food intake without alcohol and on restricted physical activity. Complementary insulin treatment is recommended whenever the BG-concentrations in a daily profile exceed 10.0 mmol/l. Oral antidiabetic drugs should be used only if they result in a marked improvement of diabetes control and no signs of liver damage appear.


A patent searcher's personal chronicle: 40 years in the evolution of a profession.
Forty years have passed since this chemist elected to attempt to become an information chemist, thus pursuing a career path he had not heard of during his undergraduate and graduate education. Much has changed during that period. Punched cards, microfilm and microfiche, coordinated term indexes, and more have come and gone. The US Patent and Trademark Office has issued more than 3 million patents, exceeding its total output in all the years that came before. Online database searching replaced prior reliance on printed indexes and classified card files, and now seeks to redefine itself to stand up against the juggernaut of the Internet. In the face of all that change the traditional abstracting and indexing function is still with us, though not without considerable reshaping. This paper surveys this landscape of change and suggests that if we are wise, we will nurture this intellectual activity far into the future.


Proinflammatory Mediators Enhance the Osteogenesis of Human Mesenchymal Stem Cells after Lineage Commitment.
Several inflammatory processes underlie excessive bone formation, including chronic inflammation of the spine, acute infections, or periarticular ossifications after trauma. This suggests that local factors in these conditions have osteogenic properties. Mesenchymal stem cells (MSCs) and their differentiated progeny contribute to bone healing by synthesizing extracellular matrix and inducing mineralization. Due to the variation in experimental designs used in vitro, there is controversy about the osteogenic potential of proinflammatory factors on MSCs. Our goal was to determine the specific conditions allowing the pro-osteogenic effects of distinct inflammatory stimuli. Human bone marrow MSCs were exposed to tumor necrosis factor alpha (TNF-α) and lipopolysaccharide (LPS). Cells were cultured in growth medium or osteogenic differentiation medium. Alternatively, bone morphogenetic protein 2 (BMP-2) was used as osteogenic supplement to simulate the conditions in vivo. Alkaline phosphatase activity and calcium deposition were indicators of osteogenicity. To elucidate lineage commitment-dependent effects, MSCs were pre-differentiated prior treatment. Our results show that TNF-α and LPS do not affect the expression of osteogenic markers by MSCs in the absence of an osteogenic supplement. In osteogenic differentiation medium or together with BMP-2 however, these mediators highly stimulated their alkaline phosphatase activity and subsequent matrix mineralization. In pre-osteoblasts, matrix mineralization was significantly increased by these mediators, but irrespective of the culture conditions. Our study shows that inflammatory factors potently enhance the osteogenic capacity of MSCs. These properties may be harnessed in bone regenerative strategies. Importantly, the commitment of MSCs to the osteogenic lineage greatly enhances their responsiveness to inflammatory signals.


Reaction between peroxynitrite and hydrogen peroxide: formation of oxygen and slowing of peroxynitrite decomposition.
Peroxynitrite, the reaction product of nitric oxide and superoxide, is a potent and versatile oxidant that can attack a wide range of targets. In this work, we studied the oxidation of hydrogen peroxide by peroxynitrite, which led to oxygen evolution. Oxygen yields increased at alkaline pH with an apparent pKa of 7.05 +/- 0.04. The maximum yields were 16% and 32% of added peroxynitrite at pH 5.9 and 7.4, respectively, assuming that two molecules of peroxynitrite are needed to produce one of oxygen. Hydroxyl radical scavengers (dimethyl sulfoxide, mannitol, ethanol, formate, and acetate) inhibited oxygen evolution to a similar extent to that predicted from their rate constants with hydroxyl radical. The apparent rate constant of peroxynitrite decomposition was zero-order in hydrogen peroxide at acidic pH. At neutral and alkaline pH, the rate of peroxynitrite disappearance decreased in the presence of millimolar concentrations of hydrogen peroxide by up to 50%. The apparent activation enthalpy and entropy for peroxynitrite decomposition increased by 1.7 kcal mol-1 and 4.7 cal mol-1 K-1, respectively, in the presence of hydrogen peroxide. We propose that an activated intermediate of peroxynitrous acid is responsible for hydrogen peroxide oxidation at acidic pH, while at more alkaline pH the formation of a stabilizing complex between hydrogen peroxide and transperoxynitrite anion is involved.


Metabolomics as a potential new approach for investigating human reproductive disorders.
Metabolomics has been emerging for several years as a global chemical phenotyping approach offering fascinating descriptive capabilities for addressing life complexity. It facilitates the understanding of the mechanisms of biological and biochemical processes in complex systems and promises new insights into specific research questions. The objective of this study was to use for the first time a metabolomic approach based on liquid chromatography high resolution mass spectrometry for characterizing an alteration of the testicular function, namely impaired semen quality. Metabolomic fingerprints were generated from serum samples collected from Danish young men presenting low, intermediate, or high sperm concentrations. Serum metabolic profiles were found to be significantly different among the three groups of volunteers. The developed methodology permitted to correlate the studied clinical parameter (i.e., sperm concentration) with the metabolite profiles generated. Peptides related to the Protein Complement C3f were identified as putative markers associated with this clinical parameter. The biological interpretation and further robustness linked to this observation remain to be further investigated, in particular to address the inter- and intraindividual variabilities.


Gulf War illness: a view from Australia.
Australia sent a small, mostly naval, deployment to the 1991 Gulf War. When papers and media concerns arose about unexplained Gulf War illnesses in Gulf War troops from other countries, Australia decided to undertake its own study of Australian veterans. Undertaking a later study, more than 10 years after the Gulf War, allowed us to incorporate some methodological improvements on previous research, such as the inclusion of a face-to-face health assessment where more objective health data could be collected in addition to using a postal questionnaire. Despite the different Gulf War experience for the mostly naval Australian group, there were remarkable consistencies in the patterns of multiple symptom reporting found in overseas studies, including the fact that no unique symptom clusters were identified. In general, this excess symptom reporting was not found to occur with excesses in more objective measures of physical health. These objective physical measures included a wide range of haematological, biochemical and serological markers, a physical examination, spirometry and a step test of fatigability. In contrast, several psychological disorders, including anxiety, post-traumatic stress disorder, depression and substance abuse, were found to occur in excess in the Australian Gulf War group and were associated with Gulf War psychological stressors. These findings have helped raise awareness in Australia of psychological health problems in deployed military personnel.


PM10 concentration and microbiological assessment of air in relation to the number of acute cases of type 1 diabetes mellitus in the Lubelskie Voivodeship. Preliminary report.
The aim of our study was to evaluate the relation between the concentration of particulate matter of less than 10 μm in diameter (PM10) in air and the effect of psychrophilic bacteria, mesophilic bacteria and mould fungi on the number of new cases of type 1 diabetes mellitus in children and adolescents in the Lubelskie Voivodeship in the years 2015-2016. Epidemiological data on the number of new cases of T1DM was obtained from the Department of Paediatric Endocrinology and Diabetology of the Medical University in Lublin. The number of births for the year 2015 and 2016 in the Lublin Voivodeship was acquired from the statistical yearbook by the Polish Central Statistical Office (GUS). Data on PM10 concentration in the Lubelskie Voivodeship was obtained from the report and annual evaluations of air quality prepared by the Voivodeship Inspectorate of Environmental Protection (WIOŚ) in Lublin. The analysis of psychrophilic bacteria, mesophilic bacteria and mould fungi in air was performed with use of the impact method and an air sampler. In the years 2015-2016 in the Lubelskie Voivodeship the number of births was 39 381 and 152 new cases of type 1 diabetes mellitus were recorded. The annual and 24-hour concentration of PM10 in air in 2015 was higher compared to 2016; however, the difference was not statistically significant. Moreover, we detected a higher number of psychrophilic bacteria 2739 vs 1000 CFU/m3 and a significantly higher number of mesophilic bacteria 92493 vs 1000 CFU/m3 than the norm specified in the Polish standard PN-89/Z-04111/02. A further analysis of air samples collected in the Lubelskie Voivodeship revealed lower a concentration of mould fungi compared to the Polish standard PN-89/Z-04111/02 (3840 vs 5000 CFU/m3, respectively). We isolated 9 types of mould fungi and 1 type of yeast-like fungus that are thought to have a negative effect on people's health. The statistical analysis revealed a relation between the number of new cases of T1DM and the number of psychrophilic bacteria (β= 2.86; p<0.05), mesophilic bacteria (β = 2.824; p<0.05) and the number of mould fungi (β=2.923; p<0.001). The analysis of linear regression revealed a relation between the number of new T1DM cases and mean annual concentration of PM10 for the year 2016 (p<0.001). However, there was no relation observed between the number of new cases of T1DM and the mean annual concentration of PM10 in air in the Lubelskie Voivodeship in 2015. Our preliminary results confirm the not yet fully explored relation between air pollution and the risk of type 1 DM in children and adolescents.


Immunogenic determinants of a neuropathogenic murine leukemia virus.
Previous studies of Cas-Br-M murine leukemia virus (MuLV) (Cas-MuLV) infection demonstrated that cytotoxic T cells (CTL) of the CD8+ phenotype play a role in resistance to the neuropathogenic effects of the virus in NFS/N mice. In the current study, we sought to identify the Cas-MuLV epitopes that are immunogenic for the CTL response. Infection of adult NFS/N mice with a well-characterized neuropathogenic variant of Friend MuLV, PVC-211 MuLV (PVC-MuLV), was not immunogenic for MuLV-specific CTL. Therefore, we constructed chimeric viruses between Cas-MuLV and PVC-MuLV. Infectious chimeras contained the Cas-MuLV env gene on a PVC-MuLV background (PVC-CasenvMuLV) and the PVC-MuLV env gene on a Cas-MuLV background (Cas-PVCenvMuLV). Cas-MuLV-specific CTL were found following inoculation of both the chimeric viruses and the parental Cas-MuLV but not the parental PVC-MuLV, despite evidence of antibody responses to both parental and chimeric MuLV. CTL generated in response to infection with PVC-CasenvMuLV and Cas-PVCenvMuLV were exclusively of the CD8+ phenotype. These results indicate that both the env and gag-pol regions of Cas-MuLV express epitopes that are immunogenic for CTL.


Microplastics in vacuum packages of frozen and glazed icefish (Neosalanx spp.): A freshwater fish intended for human consumption.
It is widely accepted that human is exposed to microplastics through food consumption, however data occurrence in foodstuffs are still little and basically limited to seafood. In this study, the presence of microplastics was investigated in icefish (Neosalanx spp.) samples sourced from various mass-market retailers in Italy, supplied as frozen, glazed and vacuum-packed product. Icefish is a small freshwater fish widely imported in Europe from China as surrogate of other fish species subjected to commercial restriction, consumed whole after cooking in several culinary preparation. The samples (~10 g of icefish from each of the 40 packs tested) were digested using a solution of 10% potassium hydroxide and filtered through a 5 μm pore-size filter. Filters of the samples were observed under a stereomicroscope and the chemical composition of the items detected were analysed by FTIR spectroscopy. A total of 163 items were counted in 37 (92.5%) samples with a mean value of 0.42±0.28 items/g w.w. Fibers were the most detected morphotype and several plastic polymers, such as polypropylene, polyethylene, polyethylene terephthalate and polystyrene, were identified by FT-IR analysis. As store-bought samples, the sources of microplastics could be substantially related to contamination during food processing. However, an intravital exposure to microplastics present in the surroundings waters cannot be ruled out. More foodstuffs need to be investigated for microplastic presence. In this study, microplastic occurrence was reported in freshwater biota intended for human consumption sampled directly from supermarket contributing to the risk assessment of human exposure to microplastics via food consumption.


Latent class analysis of eating and impulsive behavioral symptoms in Taiwanese women with bulimia nervosa.
The implications of impulsivity in its relationship with binge-eating or purging behaviors remain unclear. This study examined the patterns of eating behaviors and co-morbid impulsive behaviors in individuals with bulimia nervosa n optimally homogeneous classes using latent class analysis (LCA). All participants (n=180) were asked to complete a series of self-reported inventories of impulsive behaviors and other psychological measures. Information regarding the lifetime presence of symptoms of eating disorder was assessed by clinical interviews. LCA was conducted using eating disorder symptoms, impulsive behaviors, and the number of purging methods. Three latent classes of bulimic women were identified. These were women who exhibited relatively higher rates of purging, symptoms of impulsive behavior, and multiple purging methods (17.8%), women who used no more than one purging method with a low occurrence of impulsive behavior (41.7%), and women who showed higher rates of purging behaviors and the use of multiple purging methods with a low rate of impulsive behavior (41.7%). The impulsive sub-group had comparable severity of eating-related measures, frequency of binge-eating, and higher levels of general psychopathology than that of the other two sub-groups. This study provides empirical support for the existence of an impulsive subgroup with distinctive features among a non-Western group of BN patients. This study also suggests that mechanisms other than impulse dysregulation may exist for the development of binge-eating and purging behaviors in bulimia nervosa patients, or the mechanisms contributing to binge-eating and impulsive behaviors may be different.


Single nanotube Raman spectroscopy.
A review is presented on the observation of the resonant Raman spectra from one isolated single wall carbon nanotube, focusing on the important structural information that is provided by single nanotube spectroscopy including the (n, m) determination of the individual tubes. The special sensitivity of the radial breathing mode to the (n, m) determination is emphasized, and the corroboration of this (n, m) assignment by diameter- and chirality-dependent phenomena in other Raman modes, such as the G-band, D-band, and G'-band features is also discussed. The significance of single nanotube spectroscopy for future nanotube research in general is briefly reviewed.


Building capacity in the Mongolian health sector: a training methodology based on identified needs assessments.
Mongolian health care is moving from a centrally planned hierarchical basis towards greater decentralisation as part of overall sector wide reform. To identify key needs of health personnel to help to build capacity, we undertook research aimed at assessing priority training areas. The research results indicated gaps and weaknesses in many technical areas, but also significant problems in terms of how Mongolian health organizations function, including rigid structures, isolated management, and little internal communication. These features militate against optimal agency effectiveness. This paper discusses how specific training programs were developed based on quantitative research and an overarching organisation improvement theme emphasizing openness; communication; and participation to maximize the benefits of skills transfer and capacity development.


Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging.
Mo-MLV infection of E mu-myc transgenic mice results in a dramatic acceleration of pre-B cell lymphomagenesis. We have used provirus tagging to identify genes that cooperate with the E mu-myc transgene in B cell transformation. Here we report on the identification of four loci, pim-1, bmi-1, pal-1, and bla-1, which are occupied by proviruses in 35%, 35%, 28%, and 14% of the tumors, respectively. bmi-1, pal-1, and bla-1 represent novel common proviral insertion sites. The bmi-1 gene encodes a 324 amino acid protein with a predominantly nuclear localization. bmi-1 is highly conserved in evolution and contains several motifs frequently found in transcriptional regulators, including a new putative zinc finger motif. No genes have yet been assigned to pal-1 and bla-1. The distribution of proviruses over the four common insertion sites suggests that provirus tagging can be used not only to identify the cooperating oncogenes but also to assign these genes to distinct complementation groups in tumorigenesis.


Carcinoid metastasis to the brain.
Carcinoid tumors rarely metastasize to the brain. The objectives of the current study were to assess the frequency of brain metastasis from carcinoid tumors, determine correlates of survival, and describe treatment modalities and their outcomes. Between January 1977 and December 2003, 1633 patients with a carcinoid tumor were registered at The University of Texas M. D. Anderson Cancer Center. Of those, 24 patients (1.5%) had a diagnosis of brain metastasis. The authors collected demographic and clinical data and performed a statistical analysis. The median age at the time patients were diagnosed with brain metastasis was 60 years. The metastases were treated with whole-brain radiotherapy (WBRT) alone in 7 patients (29%), and 12 patients (50%) underwent surgical resection, 7 of whom (29%) also received WBRT. The median survival time for the entire cohort after diagnosis of the primary tumor was 2.3 years (95% confidence interval [CI], 0.5-4.1 years), and the median survival time after the diagnosis of brain metastasis was 10.0 months (95% CI, 4.0-16.0 months). The longest median survival observed after the diagnosis of brain metastasis (3.2 years) occurred in patients who underwent resection and received WBRT. In the multivariate analysis, the adjusted rate ratio for comparison of all treatments versus combination of neurosurgical intervention and WBRT was 5.7 (95% CI, 1.3-26.1; P = 0.024). A positive effect of surgery followed by WBRT on the duration of survival was detected in patients with a single metastasis (P = 0.084) as well as in those with multiple metastases (P = 0.018). Prolonged survival was observed in patients < 65 years old as well as in those who underwent surgery and received WBRT in comparison with other treatments. Whenever feasible, neurosurgical resection followed by WBRT seems to be the indicated treatment in patients with brain metastases from carcinoid tumors.


[Immigration and the relative earnings of female, young, and poorly educated workers in Canada].
"The purpose of this paper is to examine the impact of immigration on the market of some disadvantaged groups of Canadian workers, i.e., women, younger workers, and workers with low levels of schooling. The analysis is done with the micro-data from the 1981 and 1986 Canadian Censuses. Based on their distribution by industry and occupation, recent immigrants are more likely to compete with the disadvantaged groups of Canadian workers than with advantaged ones. However, an analysis of relative earnings by region shows that the relationship between the earnings differentials and the proportion of immigrants is not the same for all the disadvantaged groups. In particular, earnings differentials between men and women tend to be lower in the regions with a high proportion of immigrants than in those with a low proportion." (SUMMARY IN ENG)


Chloroquine sensitivity of Plasmodium falciparum in Shankargarh block of Allahabad district (U.P.).
Chloroquine sensitivity of Plasmodium falciparum was carried out in Shankargarh block of Allahabad district, U.P. to confirm the presence of resistant strain in the area. A total of 47 cases were subjected to in vivo extended test, of which resistance was detected in 11 cases at R-II/R-III level and in 9 cases at R-I level. One case out of 18 subjected to standard 7-day in vivo test showed resistance at R-III level. Micro in vitro test was done for 24 cases, of which growth was seen in 21 control samples. Out of these 7 cases were found to be resistant. The significance of the findings are discussed.


[Iodine 123-labeled meta-iodobenzylguanidine myocardial scintigraphy in the cases of idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy].
A 20-25% rate of antemortem misdiagnosis of idiopathic Parkinson's disease (PD) suggests that it may be difficult to clinically differentiate PD from other degenerative diseases of the central nervous system, such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA). Iodine-123 meta-iodobenzylguanidine ([123I] MIBG), an analogue of norepinephrine, is a tracer for functioning of sympathetic neurons. To investigate cardiac sympathetic function in PD, MSA, and PSP, [123I] MIBG myocardial scintigraphy was performed in 25 patients with PD, 25 patients with MSA, 14 patients with PSP, and 20 control subjects. In planar imaging studies, the heart-to-mediastinum average count ratio (H/M) was calculated for both early and delayed images. The mean value of H/M in patients with PD was significantly lower than in those with MSA, PSP, or no disease (p < 0.0001). Regardless of disease severity or intensity of anti-parkinsonian pharmacotherapy, mean values for H/M were always low in patients with PD. The mean values of H/M in patients with MSA and PSP were significantly lower than in controls (p < 0.01). There was no significant difference between the mean value of H/M in MSA with orthostatic hypotension (OH) and that in MSA without OH, and also there was no significant difference between the mean value of H/M in MSA with striatonigral degeneration and that in MSA with olivopontocerebellar atrophy. Although the mean value of H/M in PSP with amitriptyline treatment was significantly lower than that in PSP patients without amitriptyline treatment (p < 0.005), there was no significant difference between the mean value of H/M in PSP patients without amitriptyline treatment and that in controls. There was no correlation between H/M and disease duration in those three akinetic-rigid disorders that we have studied here. Thus, PD may have an abnormality of cardiac sympathetic function which has not been detected by previous cardiovascular autonomic studies. Particularly in early stages, [123I] MIBG myocardial scintigraphy may help to differentiate PD from MSA and PSP.


Dose assessment for inhalation intakes in complex, energetic environments: experience from the US Capstone study.
Because of the lack of existing information needed to evaluate the risks from inhalation exposures to depleted uranium (DU) aerosols of US soldiers during the 1991 Persian Gulf War, the US Department of Defense funded an experimental study to measure the characteristics of DU aerosols created when Abrams tanks and Bradley fighting vehicles are struck with large-caliber DU penetrators, and a dose and risk assessment for individuals present in such vehicles. This paper describes some of the difficulties experienced in dose assessment modelling of the very complex DU aerosols created in the Capstone studies, e.g. high concentrations, heterogeneous aerosol properties, non-lognormal particle size distributions, triphasic in vitro dissolution and rapid time-varying functions of both DU air concentration and particle size. The approaches used to solve these problems along with example results are presented.


Willingness to donate organs - an anonymised survey in the emergency department.
In Switzerland, 519 patients received an organ in 2020. In total, 2124 patients were on the donor organ waiting list in 2020. There are many more people who need an organ than people willing to donate one. Therefore, 43 organs had to be imported from outside of Switzerland and this number was still not sufficient. This disproportion of patients needing an organ and available donor organs is the subject of ongoing discussion. A solution to this problem might be provided by a popular initiative proposing that every single resident of Switzerland should be an organ donor, unless a person explicitly rejects organ donation. We surveyed the patients in a single tertiary care emergency department (ED) to determine whether they had an organ donor card or were registered in the Swiss National Organ Donor Registry (NODR), the frequency of willingness to donate organs and which factors were associated with being an organ donor. In a prospective anonymised survey during July 2019, we enrolled patients who visited a Swiss tertiary care ED, during one week from 8:00 to 18:00, two weeks from 14:00 to 23:00 and one week from 23:00 to 8:00. The patients completed a written, standardised and self-administrated questionnaire during the waiting time in the ED. Descriptive, uni- and multivariable logistic regression analysis were performed. We enrolled 307 ED patients, of whom 62 (20.2%) were donor card holders or were registered in the Swiss NODR. Of these, 53 (85.5%) would be willing to donate organs. The remaining nine (14.5%) were not willed to donate an organ; the reasons for this were very heterogeneous. In contrast, the two leading reasons for willingness to donate organs were: to help after death (94.3%) and to free relatives from the task of making the decision (43.4%). From the 245 (79.8%) participants who did not have an organ donor card or were not registered, 84 respondents (34.3%) lacked knowledge of this topic, 65 (26.5%) had not yet thought about the topic and 51 (20.8%) had not yet had time to take care of this issue. Blood donation (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.1-3.9; p = 0.018) or receiving a transplant in the past (OR 6.1, 95% CI 1.3-29.1; p = 0.023) and having a university degree (OR 1.8, 95% CI 1.0-3.2; p = 0.049) were factors associated with being an organ donor card holder. Only one in five ED patients had a fully completed organ donor card or were registered in the Swiss NODR. Of these, the great majority were willing to donate organs. Most of the ED patients who did not have an organ donor card or were not registered in the NODR lacked knowledge and information about the topic, had not yet thought about it or had not had time to deal with this issue. Factors such as a positive history of blood donation, organ transplantation in the past or having a university degree were associated with having an organ donor card. In order to increase the willingness to donate organs in the future, it is of immense importance to provide better information and more details and knowledge about this important topic.


Carbohydrate deposits on the surfaces of worn extended-wear soft contact lenses.
Three different commercial extended-wear soft contact lenses worn continuously by patients for at least 28 days were stained with fluorescein isothiocyanate-labeled lectins. These lectins detected the presence of alpha-linked or beta-linked D-mannose, D-glucose, D-galactose, L-fucose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, and N-acetyl neuraminic acid (sialic acid) on the surfaces of the contact lenses. These saccharides are bound to other sugars that likely account for an integral part of glycoprotein and/or glycolipid deposits on lens surfaces. These tear deposits may contribute to the chemical spoilage of the lens and, furthermore, may serve as specific receptors for pathogenic microorganisms commonly implicated in extended-wear soft contact lens-associated infectious keratitis.


Effect of repeated low-dose organophosphorothionate pesticide exposure on digoxin pharmacokinetics in rats; a possible interaction involving p-glycoprotein.
ABSTRACT Aside from acute occupational exposure, an important part of the population may be chronically exposed to the trace amounts of organophosphorothionate pesticides (OPTs) via residues in nutrients and drinking water. P-glycoprotein (P-gp) is a transmembrane protein responsible for the efflux of numerous drugs. OPTs were shown to inhibit P-gp function in vitro and increase its expression in vivo. Digoxin is a probe drug for the investigation of P-gp. To evaluate the effect of repeated low-dose OPT exposure on P-gp, commercial formulations of diluted OPT or tap water were administered to female Wistar rats for 8 consecutive days. On the ninth day each group was further divided into two groups and digoxin was administered either intraduodenally (ID) or intravenously (IV). Blood sampling and bile and urine collection were taken during 6 h at various intervals. The peak concentration in serum (C(max)) of digoxin was found to be decreased and the mean absorption time (MAT) was significantly increased in the digoxin OPT group. The mean residence time was significantly elevated in the digoxin(ID) OPT group. The biliary excretion% digoxin was significantly increased in the digoxin OPT group, while the renal excretion% digoxin rose only in the digoxin(ID) OPT group. No significant differences in time to reach C(max) (t(max)), area under the plasma concentration-time curve (AUC)(0-360), area under the moment curve (AUMC)(0-360), and bioavailability (F) were detected. In our study, repeated low-dose OPT exposure reduced the absorption and increased the excretion% digoxin, which may be related to enhanced P-gp expression. However, alterations of digoxin pharmacokinetic parameters did not change the systemic availability of digoxin.


Effectiveness of laser-assisted irrigation and passive ultrasonic irrigation techniques on smear layer removal in middle and apical thirds.
The purpose of this study was to investigate the evaluation of laser-assisted irrigation (LAI) on the removal of the smear layer as compared to passive ultrasonic irrigation (PUI). Forty-eight single-rooted, upper-central incisor teeth were selected and prepared with ProTaper rotary instruments up to size #40 (F4) at the working lengths. Specimens were divided into four groups, as follows: (a) PUI with 5 mL of 2.5% NaOCl for 60 s; (b) PUI with 2.5 mL of 17% EDTA and 2.5 mL of 2.5% NaOCl each for 30 s; (c) LAI with 5 mL of 2.5% NaOCl for 60 s; and (d) LAI with 2.5 mL of 17% EDTA and 2.5 mL of 2.5% NaOCl each for 30 s. In the PUI groups, the ultrasonically activated file was inserted 1 mm short of the working length, but in the LAI groups, the fiber tip was applied into the pulp chamber. LAI in the pulp chamber with the combination of 17% EDTA and 2.5% NaOCl removed more of the smear layer than the other groups (p < 0.018). LAI in the pulp chamber with the combination of 2.5% NaOCl and 17% EDTA better removed the smear layer than LAI applied similarly but without EDTA or PUI with the same NaOCl and EDTA combinations using an ultrasonically activated file inserted 1 mm short of the working length.


[Kcnq1ot1 promotes osteogenic differentiation and suppresses osteoclast differentiation].
To investigate the regulatory role of long non-coding RNA Kcnq1ot1 in osteoclast differentiation, osteogenic differentiation and osteoporosis. The expression of lnc-Kcnq1ot1, Bglap, Runx2, Alp, Bsp, Nfatc1, Mmp9, Ctsk and Oscar were detected by real-time quantitative PCR (qRT-PCR) in the femoral bones from mouse models of postmenopausal osteoporosis (ovariectomized mice, n=8), disuse osteoporosis (induced by tail suspension, n=14) and agerelated osteoporosis (18-month-old mice, n=8), and also in MC3T3-E1 cells during osteoblast differentiation and in murine bone marrow-derived macrophages (BMMs) and RAW264.7 cells during osteoclast differentiation. MC3T3-E1 cells with lncKcnq1ot1 knockdown by lentivirus infection were induced to differentiate into osteoblasts using osteogenic induction medium, and the expression of lnc-Kcnq1ot1, Alp and Bglap was detected with qRT-PCR and ALP activity was assessed with ALP staining. BMMs and RAW264.7 cells were transfected with siRNAs targeting lnc-Kcnq1ot1 and stimulated with RANKL and/or M-CSF, and the expression of lnc-Kcnq1ot1, Ctsk and Oscar was detected by qRT-PCR, and TRAP activity was assessed by TRAP staining. The subcellular localization of lnc-Kcnq1ot1 in MC3T3-E1 and RAW264.7 cells was determined using cell fractionation followed by qRT-PCR. The expression of lnc-Kcnq1ot1 was significantly upregulated during osteoblast differentiation but downregulated in the bone tissues of osteoporotic mice and during osteoclast differentiation (P < 0.05). Silencing lnc-Kcnq1ot1 obviously decreased the expression of Bglap and Alp (P < 0.05) and attenuated osteogenic medium-induced osteoblast differentiation. Knockdown of lnc-Kcnq1ot1 also promoted the expression of Ctsk and Oscar (P < 0.05) and aggravated RANKL-induced osteoclast differentiation. The results of cell fractionation and qRT-PCR demonstrated that lnc-Kcnq1ot1 was located mainly in the nuclei of MC3T3-E1 and RAW264.7 cells. Our data demonstrate that lnc-Kcnq1ot1 promotes osteogenic differentiation and alleviates osteoclast differentiation, suggesting the potential of lnc-Kcnq1ot1 as a therapeutic target against osteoporosis.


Synthesis and Electrochemical, Photophysical, and Self-Assembly Studies on Water-Soluble pH-Responsive Alkynylplatinum(II) Terpyridine Complexes.
A series of water-soluble pH-responsive alkynylplatinum(II) terpyridine complexes have been synthesized and characterized. The electronic absorption, emission, and electrochemical properties of the complexes have been studied. The self-assembly processes of representative complexes in aqueous media, presumably through Pt···Pt and/or π-π interactions, have been investigated by concentration- and temperature-dependent UV-vis absorption measurements and dynamic light scattering experiments. Interestingly, some of the complexes have been found to undergo induced self-assembly and disassembly in aqueous media through modulation of the pH value of the solutions, resulting in remarkable UV-vis absorption and emission spectral changes. The emission spectral changes have been rationalized by the change in the hydrophilicity of the complexes, electrostatic repulsion among the complex molecules, and/or the extent of photoinduced electron transfer (PET) quenching upon protonation/deprotonation of the pH-responsive groups on the complexes. By simple modifications of the chemical structures of the complexes, induced self-assembly/disassembly of the complexes can occur at different and/or multiple pH regions, thus allowing the probing of changes at the desired pH region by triplet metal-metal-to-ligand charge-transfer emission of the complexes in the near-infrared (NIR) region. Fixed-cell imaging experiments have further demonstrated the potential of this class of complexes as pH-responsive NIR luminescent probes in vitro, while the NIR emissions of the complexes from live cells have been found to show good differentiation of acidic organelles such as lysosomes from other cellular compartments.


Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure.
The clinical relevance of detecting minority drug-resistant human immunodeficiency virus type 1 (HIV-1) variants is uncertain. To determine the effect of pre-existing minority nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistant variants on the risk of virologic failure, we reanalyzed a case-cohort substudy of efavirenz recipients in AIDS Clinical Trials Group protocol A5095. Minority K103N or Y181C populations were determined by allele-specific polymerase chain reaction in subjects without NNRTI resistance by population sequencing. Weighted Cox proportional hazards models adjusted for recent treatment adherence estimated the relative risk of virologic failure in the presence of NNRTI-resistant minority variants. The evaluable case-cohort sample included 195 subjects from the randomly selected subcohort (51 with virologic failure, 144 without virologic failure), plus 127 of the remaining subjects who experienced virologic failure. Presence of minority K103N or Y181C mutations, or both, was detected in 8 (4.4%), 54 (29.5%), and 11 (6%), respectively, of 183 evaluable subjects in the random subcohort. Detection of minority Y181C mutants was associated with an increased risk of virologic failure in the setting of recent treatment adherence (hazard ratio, 3.45 [95% confidence interval, 1.90-6.26]) but not in nonadherent subjects (hazard ratio, 1.39 [95% confidence interval, 0.58-3.29]). Of note, 70% of subjects with minority Y181C variants achieved long-term viral suppression. In adherent patients, pre-existing minority Y181C mutants more than tripled the risk of virologic failure of first-line efavirenz-based antiretroviral therapy. NCT00013520.


Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma.
Germline mutations of the STK11/LKB1 tumour suppressor gene (19p13.3) are responsible for Peutz-Jeghers syndrome (PJS), a rare genetic disorder, which is dominantly inherited. In addition to the typical hamartomatous gastrointestinal polyps and perioral pigmented lesions, PJS is also associated with the development of tumours in various sites. No specific follow up has yet been evaluated for gene carriers. Furthermore, genetic heterogeneity has been reported, which makes genetic counselling difficult. We report here the analysis of the STK11/LKB1 locus in a series of 34 PJS families, combining the search for mutations and rearrangements in the coding sequence, allele specific expression tests, and linkage studies. Germline deleterious mutation of the STK11/LKB1 gene were identified in 70% of cases. The hypothesis of a second PJS locus was reinforced and PJS families could be divided into two groups on the basis of the presence or absence of an identified STK11/LKB1 alteration. Analysis of clinical data indicates that the cancer associated risk is markedly different in the two groups. PJS patients with no identified STK11/LKB1 mutation are at major risk for proximal biliary adenocarcinoma, an infrequent tumour in the general population. Up to 30% of PJS patients are caused by mutation in an unidentified gene that confers high susceptibility to cancer development.


Mitochondrial developmental encephalopathy with bilateral optic neuropathy related to homozygous variants in IMMT gene.
IMMT gene codes for mitofilin, a mitochondrial inner membrane protein that regulates the morphology of mitochondrial cristae. The phenotype associated with mutations in this gene has not been yet established, but functional studies carried out show that its loss causes a mitochondrial alteration, both in the morphology of the mitochondrial crests and in their function. We present two cousins from an extended highly consanguineous family with developmental encephalopathy, hypotonia, nystagmus due to optic neuropathy. The likely pathogenic homozygous c.895A>G (p.Lys299Glu) variant in the IMMT gene co-segregates with the disease and associates altered mitochondrial cristae observed by electron microscopy.


Glycine receptor is differentially expressed in the rat retina at early stages of streptozotocin-induced diabetes.
Diabetes mellitus is a metabolic disease that leads to several complications which include retinopathy. Neuronal abnormalities have been reported to appear before microvasculature alterations. We analyzed the expression levels of GlyR subunits in the retina at 7, 20, and 45 days after streptozotocin-induced diabetes to gain insight into the pathogenesis of diabetic retinopathy. We determined the mRNA and protein expression by qPCR and western blot, respectively. The mRNA and protein expression of the α1 subunit was not altered over the study period; however, they were slightly reduced in α2 yet statistically significant. While protein expression of α3 subunit was only reduced at 45 days diabetes. The mRNA and protein expression of the α4 subunit was remarkably decreased since day 7 of diabetes, remaining only ∼20% on day 45 of diabetes. Surprisingly, the mRNA of the β subunit was highly increased, while its protein levels were not changed. The decrease in GlyR α subunits expression in the retina from diabetic animals suggest a perturbation in the inhibitory glycine signaling pathway, which might be related to the visual alterations observed in diabetes.


Turning points in international labor migration: a case study of Thailand.
"This article describes the dynamics of the structural transformation of the Thai economy, labor migration and direct foreign investment and proposes an econometric model to explain the migration phenomenon. Though migration shifts have been significantly influenced by political factors such as the Gulf crisis and tensions with Saudi Arabia, economic factors such as the Thai government's liberalization of markets and the expansion of trade and direct foreign investment have contributed to changes in labor market needs. The economic conditions of a shift from net exporter to net importer for labor are posited in the model. The empirical results reveal a turning point in labor migration from Thailand and also confirm the contribution of commodity export in place of labor export in creating employment and income."