The effect of dimethylnitrosamine on the synthesis of high-mobility group non-histone proteins in regenerating rat liver.
A single injection of dimethylnitrosamine (DMN) given to adult rats induces hepatocellular carcinoma if given during the period of restorative hyperplasia following partial hepatectomy. The effect of DMN on the sequence of biochemical events in regenerating liver is therefore of interest. As carcinogenesis is likely to involve a change in control of gene expression, and as evidence suggests that non-histone chromosomal proteins (NHP) are involved in gene control, the effect of DMN on synthesis of NHP in regenerating liver was studied. A well-defined group of NHP, the high mobility group (HMG), known to be specifically associated with DNA active in transcription, were investigated. Partial hepatectomy was found to cause a large increase in incorporation of [3H]lysine into HMG proteins; this did not occur immediately, but was apparent at the time of DNA synthesis and of mitosis. DMN did not alter the relative amounts of different HMG proteins in relation to histone H1, but the carcinogen caused a considerable reduction in incorporation of [3H]lysine. This decreased synthesis of the proteins which may function as gene derepressors may well be relevant in carcinogenesis.


Evaluation of the Antimicrobial Properties of the Essential Oil of Myrtus communis L. against Clinical Strains of Mycobacterium spp.
Mycobacterium tuberculosis is the etiological agent of tuberculosis. The World Health Organization has estimated that 8 million of people develop active TB every year and the situation is complicated by an increase of Mycobacterium tuberculosis strains resistant to drugs used in antitubercular therapy: MDR and XDR-TB. Myrtle leaf extracts, used as an antiseptic in Sardinian traditional medicine, have strong antibacterial activity as several investigations showed. In this study we investigated the antimicrobial properties of the essential oil of Myrtus communis against clinical strains of M. tuberculosis and M. paratuberculosis.


Comparison of efficacy in adjuvant chemotherapy regimens in patients with radically resected gastric cancer : a propensity-matched analysis.
We conducted the retrospective study to compare the efficacy of monotherapies versus two-drug regimens as postoperative chemotherapy for patients with radically resected gastric cancer. At a median follow-up of 5.3 years, no significant difference in terms of OS was observed between two groups, neither before nor after matching. After matching, median DFS was statistically significant between group A and B (median, 67.5 vs 101.0 months, respectively; hazard ratio [HR], 0.65; 95% CI, 0.45 to 0.95; P=0.027), which meant doublets prolonged DFS. In subgroup analysis, the patients of stage III receiving doublet achieved better OS than those receiving monotherapy. People who received doublet and were less than 65 years old, or male patients, or in T4 stage, or in N2 stage, or receiving subtotal gastrectomy had better DFS than those with monotherapy. A data set including 501 patients (monotherapy, n=107; doublet, n=394) was matched between the two groups (n=107 patients per group) using the propensity-matched study. The primary and secondary endpoint was overall survival(OS) and disease-free survival(DFS), respectively. Survival data was compared using the Kaplan-Meier method and Cox proportion hazards models for univariate and multivariate analyses. The dual regimens seemed not to add overall survival benefits to patients receiving curative gastrectomy, compared with single-agent fluoropyrimidine as postoperative chemotherapy. However, dual regimens showed better disease-free survival.


Risk Score based on microRNA expression signature is independent prognostic classifier of glioblastoma patients.
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.


The impact of pneumococcal conjugate vaccines on carriage of and disease caused by Streptococcus pneumoniae serotypes 6C and 6D in southern Israel.
The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) followed by PCV13 resulted in a dramatic reduction in carriage and disease rates of Streptococcus pneumoniae (Sp) serotype 6B (Sp6B) and Sp6A. The structural modifications of the capsule of Sp6A and Sp6B to become Sp6C and Sp6D, respectively, raised a concern that eradication of Sp6A/Sp6B by PCV could be accompanied by an increase in Sp6C/Sp6D. This study examines the dynamics and clonal distribution of Sp6C/Sp6D relative to Sp6A/Sp6B during 1999-2014, pre- and post-PCV implementation. Sp were cultured from Blood/CSF and MEF of children <2 years, and from conjunctiva and nasopharynx of children <5 years. PCR was applied for Sp6C and Sp6D identification. Clonality was determined by PFGE and MLST. PCV introduction resulted in decreased carriage rates and conjunctivitis caused by serogroup 6 serotypes. Incidence of Sp6A, Sp6B and Sp6D in otitis media dropped gradually along with PCV7/13 introduction, whereas Sp6C rates increased in the PCV7 period and then decreased following PCV13 implementation. In invasive pneumococcal disease, complete elimination of serogroup 6 was found in the PCV era. Similar clonal composition was found for Sp6C and Sp6D pre- and post-PCV. We conclude that Sp6C and Sp6D do not act as replacement serotypes for Sp6A and Sp6B following vaccination with PCV13. The major Sp6C and Sp6D clones present pre-PCV persisted also post-PCV implementation, suggesting that these clones possess an advantage retained post-vaccination.


Targeting Angiogenesis in Squamous Cell Carcinoma of the Head and Neck: Opportunities in the Immunotherapy Era.
Despite the lack of approved anti-angiogenic therapies in squamous cell carcinoma of the head and neck (SCCHN), preclinical and more recent clinical evidence support the role of targeting the vascular endothelial growth factor (VEGF) in this disease. Targeting VEGF has gained even greater interest following the recent evidence supporting the role of immunotherapy in the management of advanced SCCHN. Preclinical evidence strongly suggests that VEGF plays a role in promoting the growth and progression of SCCHN, and clinical evidence exists as to the value of combining this strategy with immunotherapeutic agents. Close to 90% of SCCHNs express VEGF, which has been correlated with a worse clinical prognosis and an increased resistance to chemotherapeutic agents. As immunotherapy is currently at the forefront of the management of advanced SCCHN, revisiting the rationale for targeting angiogenesis in this disease has become an even more attractive proposition.


Usefulness of the Universal Adapter for Smartphones® in a Mannequin Study.
Because of the shape of a double-lumen tube (DLT), it is more difficult to use for intubation than an ordinary endotracheal tube. We prospectively investigated the usefulness of the Airtraq DL® attached to the Universal Adapter for Smartphones® for DLT intubation. At Tokai University Hachioji Hospital, anesthesiologists with ≥ 5 years' clinical experience intubated a tracheal intubation training mannequin with DLTs using the Airtraq DL® (Airtraq-alone phase) and the Airtraq DL® attached to the Universal Adapter for Smartphones® (adapter phase), and the time required was measured. The mean time required for intubation was shorter in the adapter phase than in the Airtraq-alone phase for all anesthesiologists (adapter phase, 9.05±2.48 seconds; Airtraq-alone phase, 10.67±2.19 seconds). The use of Airtraq DL® a ttached to t he Universal Adapter for Smartphones® significantly reduced the time required for DLT intubation. Furthermore, the combination of these devices was found to be useful and safe for DLT intubation because they provide a significant amount of information on the area from the oral cavity to the opening of the trachea and have high educational value because their combined use allows several physicians to share imaging information.


Silica gel-catalyzed one-pot syntheses in water and fluorescence properties studies of 5-amino-2-aryl-3H-chromeno[4,3,2-de][1,6]naphthyridine-4-carbonitriles and 5-amino-2-aryl-3H-quinolino[4,3,2-de][1,6]naphthyridine-4-carbonitriles.
The silica gel-catalyzed synthesis of 5-amino-2-aryl-3H-chromeno[4,3,2-de][1,6]naphthyridine-4-carbonitriles and 5-amino-2-aryl-3H-quinolino[4,3,2-de][1,6]naphthyridine-4-carbonitriles were simply achieved upon the one-pot cascade reaction of malononitrile with substituted 2-hydroxyacetophenone (or 2-aminoacetophenone) and aromatic aldehyde in aqueous media. The mechanistic investigation results based on electrospray ionization mass spectrometry (ESI-MS) indicated that malononitrile displayed a dual role during this transformation. Thirteen bonds were cleaved and 12 new bonds were constructed in the formation of 5-amino-2-aryl-3H-chromeno[4,3,2-de][1,6]naphthyridine-4-carbonitriles, while only 2 H(2)O molecules were removed. The fluorescence properties screening showed five new compounds have high fluorescence quantum yields.


Tip60 acetyltransferase activity is controlled by phosphorylation.
Here we show that the phosphorylation of histone acetyltransferase Tip60, a target of human immunodeficiency virus, type 1-encoded transactivator Tat, plays a crucial role in the control of its catalytic activity. Baculovirus-based expression and purification of Tip60 combined with mass spectrometry allowed the identification of serines 86 and 90 as two major sites of phosphorylation in vivo. The phosphorylation of Tip60 was found to modulate its histone acetyltransferase activity. One of the identified phosphorylated serines, Ser-90, was within a consensus cyclin B/Cdc2 site. Ser-90 was specifically phosphorylated in vitro by the cyclin B/Cdc2 complex. Accordingly, the phosphorylation of Tip60 was enhanced after drug-induced arrest of cells in G(2)/M. This G(2)/M-dependent phosphorylation of Tip60 was abolished by treating cells with a specific inhibitor of the cyclin-dependent kinase, roscovitin. All together, these results strongly suggest a G(2)/M-dependent control of Tip60 activity.


Pharmacology and therapeutic applications of enediyne antitumor antibiotics.
The natural compounds that interfere with cellular DNA such as enediyne antitumor antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the enediyne antitumor agents that are approved for clinical use and undergoing pre-clinical or clinical evaluation are reviewed. Most enediyne compounds have shown potent activity against the proliferation of various cancer cells, including cells that display resistance to other chemotherapeutic drugs. Enediyne derivatives, such as an immunoconjugate composed of an enediyne compound and monoclonal antibody, reveal stronger activity and selectivity for human cancer cells. The mechanism underlying the anticancer activity of these enediyne antitumor agents may mainly lie in their generation of DNA double-strand breaks. Increasing evidence shows that the enediyne-induced DNA double-strand breaks can engage the activation of DNA damage response proteins, arresting cell cycle progression and eventually leading to apoptotic cell death. Continued investigation of the mechanisms of action and development of new enediyne derivatives and conjugates may provide more effective therapeutics for cancer treatments.


Maladaptive aortic properties in children after palliation of hypoplastic left heart syndrome assessed by cardiovascular magnetic resonance imaging.
The status of the reconstructed aorta in hypoplastic left heart syndrome is considered an important determinant of long-term prognosis. Therefore, we assessed the anatomy, elastic properties, and viability of the aorta and right ventricular function in patients with hypoplastic left heart syndrome by cardiovascular magnetic resonance imaging. Cardiovascular magnetic resonance imaging was performed in 40 patients with hypoplastic left heart syndrome (age, 6.0±2.2 years) and 13 control subjects (age, 6.6±2.2 years). Aortic dimensions and distensibility were calculated at different locations of the aorta using gradient-echo cine imaging at 3.0 T. Additionally, pulse-wave velocity, right ventricular ejection fraction, and aortic late gadolinium enhancement for viability assessment were measured. Compared with control subjects, patients with hypoplastic left heart syndrome had increased axial diameters of the aortic root (36.0±5.5 versus 24.1±2.7 mm/m(2); P<0.01), ascending aorta (32.0±5.0 versus 21.3±1.5 mm/m(2); P<0.01), and transverse aortic arch (22.7±5.2 versus 18.7±2.5 mm/m(2); P<0.01). Wall distensibility was reduced in the ascending aorta (4.1±2.4 versus 13.5±7.2 10(-3) mm Hg(-1); P<0.01) and transverse aortic arch (5.4±3.6 versus 10.3±3.5 10(-3) mm Hg(-1); P<0.01). Pulse-wave velocity trended higher in patients (P=0.06). Reduced distensibility in the ascending aorta correlated with the amount of late gadolinium enhancement in a volume that included the aortic root and the ascending aorta (r=-0.72, P<0.01), and both parameters correlated with decreased right ventricular ejection fraction. Adverse aortic properties post palliation of hypoplastic left heart syndrome manifest themselves by aortic dilatation, decreased distensibility, and increased volume of nonviable aortic wall tissue. The negative association between aortic late gadolinium enhancement and right ventricular ejection fraction suggests unfavorable aortic-ventricular coupling. The potential impact of these findings on long-term right ventricular function should be evaluated in future studies.


Chiral Recognition of Self-Assembled Peptides on MoS2 via Lattice Matching.
Chiral recognition of peptides on solid surfaces has been studied for a better understanding of their assembly mechanism toward its applications in stereochemistry and enantioselective catalysis. However, moving from small peptides such as dipeptides, understanding the chiral recognition of larger biomolecules such as oligopeptides or peptides with a larger sequence is challenging. Furthermore, their intrinsic mechanism for chiral recognition in liquid conditions was poorly investigated experimentally. Here, we used in/ex situ atomic force microscopy (AFM) to investigate the chiral recognition of self-assembled structures of l/d-type peptides on molybdenum disulfide (MoS2). We chose single-layer MoS2 with a triangular shape as a substrate for the self-assembly of peptides. The facet edges of MoS2 were utilized as a landmark to identify the crystallographic orientation of their ordered structures. We found both peptide enantiomers formed nanowires on MoS2 with a mirror symmetry according to the facet edges of MoS2. From in situ AFM measurements, we found a dimension of a unit cell in the self-assembled structure and proposed a model of lattice matching between peptides and MoS2 lattice. The lattice matching for chiral recognition was further investigated by changing peptide sequences and surface lattice from MoS2 to graphite. This work further deepened the understanding of biomolecular chiral recognition and will lead us to rationally design specific morphologies and conformations of chiral self-assembled structures of peptides with expected functions in the future.


Modeling the spread of capripoxvirus among livestock and optimal vaccination strategies.
Capripox is an important transboundary animal disease that is endemic across Africa, the Middle East, and some parts of Asia. The disease is highly contagious and considered to be a major obstacle causing significant economic loses in many agricultural areas. In this study, a mathematical model is developed to describe the transmission dynamics of capripoxvirus (CaPV) among livestock. This proposed model incorporates direct and indirect transmission of CaPV, together with two vaccination strategies, to investigate their effects on the severity of outbreaks and the prevalence of CaPV among the livestock population. The results suggest that ratio of potential vectors to livestock, successful probability of infection, vaccination rates, waning rate of vaccine-conferred protection, and virus introduction time play crucial roles in determining the outbreak severity and the prevalence level. The results also show that it is optimal to vaccinate newborns at the maximum effort throughout the control program and moderately increase vaccination rate for a susceptible pool to reach its maximum level after the outbreak.


Extended producer responsibility for packaging wastes and WEEE - a comparison of implementation and the role of local authorities across Europe.
A comparison of the implementation of extended producer responsibility (EPR) to packaging waste and waste electrical and electronic equipment (WEEE) is presented for a representative sample of eleven European Union countries based on five indicators: stakeholders and responsibilities; compliance mechanisms; role of local authorities; financing mechanisms and merits and limitations, with four countries selected for more detailed case study analysis. Similarities, trends and differences in national systems are highlighted with particular focus on the role of local authorities and their relationship with obligated producers and the effect on the operation and success of each system. The national systems vary considerably in design, in terms of influence of pre-existing policy and systems, methods of achieving producer compliance (multiple or single collective schemes), fee structures, targets, waste stream prioritization and local authority involvement. Differing approaches are evident across all member states with respect to the role played by local authorities, responsibility apportioned to them, and the evolution of working relationships between obligated producers and municipalities. On the whole, EPR for packaging and WEEE has been successfully implemented throughout Europe in terms of Directive targets. It is, however, clear that the EPR systems currently in application across Europe differ primarily due to contrasting opinion on the legitimacy of local authorities as stakeholders and, in some cases, a fear on the part of industry of associated costs. Where local authorities have been engaged in the design and implementation of national systems, existing infrastructure used and defined roles established for producers and local authorities, results have been significantly more positive than in the cases where local authorities have had limited engagement.


Electrophilicity of Hoveyda-Grubbs Olefin Metathesis Catalysts as the Driving Force that Controls Initiation Rates.
The dissociative mechanism of initiation for a series of Hoveyda-Grubbs type metathesis catalysts modified at the para and meta positions in the isopropoxybenzylidene ligand is investigated by means of DFT calculations. The electron donating/withdrawing capacity of the ligand was screened through the incorporation of various substituents such as halogens, nitro, alkoxides, ketones, esters, amines, and amides. Variations in structural parameters, energy barriers for the Ru-O bond dissociation, and Ru-O bond strength were examined as a function of the Hammett constant. It was found that electronic properties of the catalysts such as chemical potential, hardness, and electrophilicity correlate linearly with the dissociative energy barriers. These findings enable a systematic rationalization and prediction of rate of precatalyst initiation through the calculation of only the HOMO-LUMO gap of catalysts, as the faster the initiation, the more electrophilic the catalyst.


Effects of arm exercise on serum glucose response in type 2 DM patients.
The aims of the study were to examine the influence of upper extremity exercise on glucose response and to establish a predictive model of changes in serum glucose under different exercise intensities and durations. Thirty-three type 2 DM patients who met the selection criteria were selected. An arm cycle ergometer exercise test was conducted, and then 12 arm exercise sessions were arranged based on different exercise intensities (40%, 60%, and 80% of maximal workload) and exercise durations (10, 20, 30, and 40 min). Serum glucose levels were measured before and after each exercise session. Serum glucose levels significantly decreased after arm exercise regardless of different intensities or durations. However, no interaction effect (intensity x duration) or main effect in exercise intensity was observed, but a significant main effect in exercise duration was observed (F = 11.756, p <.0001). Also exercise duration was a significant predictor of serum glucose changes after arm exercise. These results suggest that arm exercise can play a useful role in glycemic control for type 2 DM patients and exercise duration is a key factor in determining serum glucose response under upper-extremity exercise.


An international cross-sectional investigation on social media, fitspiration content exposure, and related risks during the COVID-19 self-isolation period.
With the global COVID-19 pandemic, governments from many countries in the world implemented various restrictions to prevent the SARS-Cov-2 virus's spread, including social distancing measures, quarantine, in-home lockdown, and the closure of services and public spaces. This led to an in-creased use of social media platforms to make people feel more connected, but also to maintain physical activity while self-isolating. Concerns about physical appearance and the desire to keep or reach a muscular and toned ideal body, might have further reinforced the engagement in fitness-related social media activities, like sharing progresses in training achievements or following more fitness contents on popular profiles. To better understand the underlying relation among these factors, the present study investigates 729 responses to the Exercise Addiction Inventory (EAI), the Appearance Anxiety Inventory (AAI), the Self-Compassion Scale (SCS) and their association to social media usage and compares the results cross-culturally in five countries (Spain, Lithuania, United Kingdom, Japan, and Hungary). Findings highlight significant differences between males and females, espe-cially in regard to the time spent online (U = 477.5, p = 0.036). Greater levels of appearance anxiety were associated with the exposure to fitness-related contents on social media. These results strongly confirm the previously highlighted association between fitspiration media and body image anxiety predominantly in females. Clinical implications and future considerations in terms of prevention and treatment in a situation of global emergency are also discussed.


Causation and space-time.
This paper considers the physical accounts of causation in terms of conserved quantities in the light of the theory of general relativity. As it is rather well-known among physicists, there are several difficulties with the notions of conservation and localization of the (gravitational) energy-momentum within general relativity. We first begin to review the so-called conserved quantity theory of causation mainly due to Dowe and Salmon, then we discuss some consequences of these difficulties for this physical account of causation. We argue that these difficulties are due to the fundamental nature of the space-time structure as described by GR, which the conserved quantity theory of causation does not account for.


Decline in air pollution and change in prevalence in respiratory symptoms and chronic obstructive pulmonary disease in elderly women.
While adverse effects of exposure to air pollutants on respiratory health are well studied, little is known about the effect of a reduction in air pollutants on chronic respiratory symptoms and diseases. We investigated whether different declines in air pollution levels in industrialised and rural areas in Germany were associated with changes in respiratory health over a period of about 20 years. We used data from the SALIA cohort study in Germany (Study on the influence of Air pollution on Lung function, Inflammation and Aging) to assess the association between the prevalence of chronic obstructive pulmonary disease (COPD) and chronic respiratory symptoms and the decline in air pollution exposure. In 1985-1994, 4874 women aged 55-years took part in the baseline investigation. Of these, 2116 participated in a questionnaire follow-up in 2006 and in a subgroup of 402 women lung function was tested in 2008-2009. Generalized estimating equation (GEE) models were used to estimate the effect of a reduction in air pollution on respiratory symptoms and diseases. Ambient air concentrations of particulate matter with aerodynamic size < 10 microm (PM10) declined in average by 20 microg/m3. Prevalence of chronic cough with phlegm production and mild COPD at baseline investigation compared to follow-up was 9.5% vs. 13.3% and 8.6% vs. 18.2%, respectively. A steeper decline of PM10 was observed in the industrialized areas in comparison to the rural area, this was associated with a weaker increase in prevalence of respiratory symptoms and COPD. Among women who never smoked, the prevalence of chronic cough with phlegm and mild COPD was estimated at 21.4% and 39.5%, respectively, if no air pollution reduction was assumed, and at 13.3% and 17.5%, respectively, if air pollution reduction was assumed. We concluded that parallel to the decline of ambient air pollution over the last 20 years in the Ruhr area the age-related increase in chronic respiratory diseases and symptoms appears to attenuate in the population of elderly women.


The subperiosteal implant as a viable long-term treatment modality in the severely atrophied mandible: a patient's 40-year case history.
Subperiosteal implants have been a treatment modality for atrophied edentulous mandibles for almost 50 years. A case is presented tracing a patient's 40-year history with treatment of his severely atrophied fully edentulous mandible with a subperiosteal implant and removable implant-borne prosthesis. The subperiosteal implant should be considered as a long-term treatment option in those patients who are unable to wear a lower full denture due to resorption of the ridge and osseous defects that provide inadequate bone for placement of endosseous blade- or root-form implants. This case demonstrates the long-term viability of the subperiosteal implant.


Neural differentiation of patient specific iPS cells as a novel approach to study the pathophysiology of multiple sclerosis.
The recent introduction of technologies capable of reprogramming human somatic cells into induced pluripotent stem (iPS) cells offers a unique opportunity to study many aspects of neurodegenerative diseases in vitro that could ultimately lead to novel drug development and testing. Here, we report for the first time that human dermal fibroblasts from a patient with relapsing-remitting Multiple Sclerosis (MS) were reprogrammed to pluripotency by retroviral transduction using defined factors (OCT4, SOX2, KLF4, and c-MYC). The MSiPS cell lines resembled human embryonic stem (hES) cell-like colonies in morphology and gene expression and exhibited silencing of the retroviral transgenes after four passages. MSiPS cells formed embryoid bodies that expressed markers of all three germ layers by immunostaining and Reverse Transcriptase (RT)-PCR. The injection of undifferentiated iPS cell colonies into immunodeficient mice formed teratomas, thereby demonstrating pluripotency. The MSiPS cells were successfully differentiated into mature astrocytes, oligodendrocytes and neurons with normal karyotypes. Although MSiPS-derived neurons displayed some differences in their electrophysiological characteristics as compared to the control cell line, they exhibit properties of functional neurons, with robust resting membrane potentials, large fast tetrodotoxin-sensitive action potentials and voltage-gated sodium currents. This study provides for the first time proof of concept that disease cell lines derived from skin cells obtained from an MS patient can be generated and successfully differentiated into mature neural lineages. This represents an important step in a novel approach for the study of MS pathophysiology and potential drug discovery.


Glomerular filtration rate and 10-year mortality in a 70-year-old community-dwelling Japanese population.
The equation for Japanese estimated glomerular filtration rate (eGFR) was revised by measuring GFR by inulin clearance. The association of the new eGFR with all-cause mortality and mortality from cardiovascular disease (CVD) was assessed in an elderly Japanese population. Seventy-year-old subjects, residents of Niigata, Japan, participated. Baseline examinations were carried out in June 1998. The new eGFR measure, 194 × (serum creatinine)-1.094 × Age-0.287 × (0.739 if female), was calculated. According to eGFR results, subjects were classified into normal or slightly impaired (≥60 mL/min/1.73 m2), moderately impaired (40-59 mL/min/1.73 m2) and severely impaired (<40 mL/min/1.73 m2). Participants were under survey for 10 years. The overall survival rate with the Kaplan-Meier method was shorter in subjects with severely impaired eGFR than in those with normal, slightly or moderately impaired eGFR. Similarly, mortality from CVD was higher for individuals with severely impaired eGFR than those with normal or slightly impaired eGFR. There were no associations of mortality from cancer or pneumonia with eGFR. The hazard ratio by the Cox proportional regression model for total mortality was 3.9 times higher in the severely impaired group than in normal or slightly impaired groups, with adjustment for confounding factors. Mortality from CVD was 13.6 times higher in the former than in the latter, with adjustment. There is an association of the new Japanese eGFR with total mortality and CVD mortality, suggesting that the new equation may be independently predictive of all-cause mortality and mortality from CVD in the general 70- year-old Japanese population.


The effects of smoking and nicotine ingestion on exercise heat tolerance.
Smoking has a thermogenic effect and is associated with low physical performance. Nevertheless, a direct, quantitative effect of acute smoking on exercise heat tolerance has not been reported. Sixteen healthy young male volunteers, eight cigarette smokers, and eight non-smokers participated in the study. All subjects performed a maximal oxygen consumption test (VO2max) and a standardized heat tolerance test (HTT) after at least 12 h without smoking under the following conditions: no nicotine exposure, 10 min after nicotine exposure (2 mg nicotine lozenge), and 10 min after smoking two cigarettes (0.8 mg nicotine in each cigarette, smokers only). There was no significant effect of nicotine exposure on physiological performance and heat tolerance in the non-smokers group. In the smokers group, cigarette smoking, but not nicotine ingestion, resulted with higher heart rate (by 9±9 bpm) at the end of the HTT (p<0.05). Moreover, both smoking and nicotine ingestion increased smokers' rectal temperature at the end of the HTT (by 0.24±0.16°C and 0.21±0.26°C, respectively, p<0.05) and were associated with higher sweat rate during the HTT (by 0.08±0.07 g/h and 0.06±0.08 g/h, respectively, p<0.05). Heart rate variability (HRV) analysis also revealed a higher LF/HF (low frequency/high frequency) ratio after exposure to nicotine and smoking in the smokers group compared with no exposure (2.13±2.57 and 2.48±2.76, respectively, p<0.05), indicating a higher sympathetic tone. According to this preliminary study, cigarette smoking and nicotine ingestion increase the physiological strain during a HTT in smokers. Acute smoking may, therefore, increase heat intolerance and the risk to heat injuries.


Large modulation of zero-dimensional electronic states in quantum dots by electric-double-layer gating.
Electrical manipulation and read-out of quantum states in zero-dimensional nanostructures by nano-gap metal electrodes is expected to bring about innovation in quantum information processing. However, electrical tunability of the quantum states in zero-dimensional nanostructures is limited by the screening of gate electric fields. Here we demonstrate a new way to realize wide-range electrical modulation of quantum states of single self-assembled InAs quantum dots (QDs) with a liquid-gated electric-double-layer (EDL) transistor geometry. The efficiency of EDL gating is 6-90 times higher than that of the conventional solid gating. The quantized energy level spacing is modulated from ~15 to ~25 meV, and the electron g-factor is electrically tuned over a wide range. Such a field effect tuning can be explained by the modulation in the confinement potential of electrons in the QDs. The EDL gating on the QDs also provides potential compatibility with optical manipulation of single-electron charge/spin states.


Light microscopic, cytochemical and ultrastructural studies of a rat odontogenic epithelial cell line.
An odontogenic epithelial cell line, ROE-2B, was established by propagating disaggregated immature, unmineralized maxillary third molar tooth germs from 11-day old Sprague-Dawley rats on a feeder layer of Mitomycin-C treated NIH 3T3 embryonic mouse fibroblasts. The cell line has been maintained for more than 6 months and through 7 passages. Light microscopic examination of cells revealed colonies with epithelial morphology. Electron microscopic examination confirmed the epithelial nature by the demonstration of tonofilaments, desmosomes and basal lamina. Cells were also shown to have secretory vacuoles, an abundance of granular endoplasmic reticulum, free ribosomes, Golgi complex and mitochondria. Surface activity in the form of pseudopodia-like projections and micropinocytosis were noted. Epithelial cells forming keratin were demonstrated by a positive histochemical reaction with Rhodanile Blue. Immunohistochemical studies showed a positive reaction for CAM 5.2 indicating that the ROE-2B cells express the cytokeratins of simple or glandular epithelia. The ROE-2B cell line will be useful for studies on in vitro biological behaviour of odontogenic epithelial cells, and may allow the establishment of in vitro models of odontogenic tumours.


Does Mandated Treatment Benefit Youth? A Prospective Investigation of Adolescent Justice System Involvement, Treatment Motivation, and Substance Use Outcomes.
The majority of adolescents treated for substance use disorder (SUD) in the United States are now referred by the criminal justice system. Little is known, however, regarding how justice-system involvement relates to adolescent community treatment outcomes. Controversy exists, also, over the extent to which justice system involvement reflects a lack of intrinsic motivation for treatment. This study examined the relation between justice system referral and reported reason for treatment entry and tested the extent to which each predicted treatment response and outcome. Adolescent outpatients (N = 127; M age = 16.7, 24% female) with varying levels of justice-system involvement (i.e., no justice system involvement [No-JSI; n = 63], justice-system involved [JSI; n = 40], justice system involved-mandated [JSI-M; n = 24]) and motivation levels (i.e., self-motivated [n = 40], externally-motivated [n = 87]) were compared at treatment intake. Multilevel mixed models tested these groups' effects on percent days abstinent (PDA) and odds of heavy drinking (HD) over 12 months. JSI-M were less likely to be self-motivated compared to No-JSI or JSI (p = 0.009). JSI-M had higher PDA overall, but with significant declines over time, relative to no-JSI. Self-motivated patients did not differ from externally-motivated patients on PDA or HD. Mandated adolescent outpatients were substantially less likely to report self-motivated treatment entry. Despite the notion that self-motivated treatment entry would be likely to produce better outcomes, a judicial mandate appears to predict an initially stronger treatment response, although this diminishes over time. Ongoing monitoring and/or treatment may be necessary to help maintain treatment gains for justice system-involved adolescents.


Use of multiple monoclonal antibodies to characterize the major microtubule-associated protein in sea urchin eggs.
Microtubules assembled from sea urchin eggs with the use of taxol contain a 77,000-dalton protein as the major nontubulin component [Vallee and Bloom (1983): Proc Natl. Acad. Sci. U.S.A. 80:6259-6263]. We have raised five monoclonal antibodies to this protein to aid in its characterization. Immunoblot analysis of the sea urchin microtubule purification fractions indicated that the protein copurified quantitatively with microtubules. All five antibodies stained the mitotic spindle of dividing sea urchin eggs by immunofluorescence microscopy, indicating that the protein was a component of the mitotic spindle and suggesting that it was actually localized on microtubules in vivo. Immunofluorescent staining of higher resolution was observed in a subpopulation of the coelomic cells found in adult sea urchins, confirming that the 77,000-dalton protein is indeed present on microtubules in vivo. Because taxol was not used for the immunofluorescence experiments, we conclude that the microtubule-associated protein (MAP)-like behavior of the 77,000-dalton protein in vitro was not induced artifactually by taxol. To determine whether this protein is a component of sea urchin microtubules in general, cilia obtained from blastula stage embryos and sperm tail flagella were analyzed with the antibodies. The protein was undetectable by both immunoblot analysis and immunofluorescence microscopy in both preparations of axonemal microtubules. These results indicated that the 77,000-dalton MAP is restricted to cytoplasmic and mitotic microtubules in the sea urchin. Furthermore, in view of its particular abundance in embryos, whose microtubules are devoted substantially to mitosis, the 77,000-dalton MAP is likely to play an important role in regulating the activity of mitotic spindle microtubules in the sea urchin.


Strategies for maximizing growth in puberty in children with short stature.
The approach to the child with growth retardation who is in puberty remains an important clinical challenge. The use of high-dose growth hormone (GH), suppression of puberty with GnRH analogs in combination with GH, and the use of selective inhibitors of the aromatase enzyme with aromatase inhibitors (also in combination with GH) are all therapeutic choices that have been studied. Aromatase blockade effectively blocks estrogen production in males with a reciprocal increase in testosterone, and a new generation of aromatase inhibitors, including anastrozole, letrozole and exemestane, is under investigation in adolescent subjects with severe growth retardation. This class of drugs, if judiciously used for a window of time, offers promise as an adjunct treatment of growth delay in pubertal patients with GH deficiency, idiopathic short stature, testotoxicosis, and other disorders of growth. These evolving uses of aromatase inhibitors, however, represent off-label use of the product, and definitive data on their efficacy are not available for each of the conditions mentioned. Safety issues regarding bone health also require further study.


Direct Intercellular Communications and Cancer: A Snapshot of the Biological Roles of Connexins in Prostate Cancer.
Tissue homeostasis is the result of a complex intercellular network controlling the behavior of every cell for the survival of the whole organism. In mammalian tissues, cells do communicate via diverse long- and short-range communication mechanisms. While long-range communication involves hormones through blood circulation and neural transmission, short-range communication mechanisms include either paracrine diffusible factors or direct interactions (e.g., gap junctions, intercellular bridges and tunneling nanotubes) or a mixture of both (e.g., exosomes). Tumor growth represents an alteration of tissue homeostasis and could be the consequence of intercellular network disruption. In this network, direct short-range intercellular communication seems to be particularly involved. The first type of these intercellular communications thought to be involved in cancer progression were gap junctions and their protein subunits, the connexins. From these studies came the general assumption that global decreased connexin expression is correlated to tumor progression and increased cell proliferation. However, this assumption appeared more complicated by the fact that connexins may act also as pro-tumorigenic. Then, the concept that direct intercellular communication could be involved in cancer has been expanded to include new forms of intercellular communication such as tunneling nanotubes (TNTs) and exosomes. TNTs are intercellular bridges that allow free exchange of small molecules or even mitochondria depending on the presence of gap junctions. The majority of current research shows that such exchanges promote cancer progression by increasing resistance to hypoxia and chemotherapy. If exosomes are also involved in these mechanisms, more studies are needed to understand their precise role. Prostate cancer (PCa) represents a type of malignancy with one of the highest incidence rates worldwide. The precise role of these types of direct short-range intercellular communication has been considered in the progression of PCa. However, even though data are in favor of connexins playing a key role in PCa progression, a clear understanding of the role of TNTs and exosomes is needed to define their precise role in this malignancy. This review article summarizes the current view of the main mechanisms involved in short-range intercellular communication and their implications in cancer and delves into the biological, predictive and therapeutic role of connexins in PCa.


Comparison of active and electrostimulated recovery strategies after fatiguing exercise.
The purpose of this study was to compare an electrostimulated to an active recovery strategy after a submaximal isometric fatiguing exercise. Nineteen healthy men completed three sessions (separated by at least 4 weeks) which included a knee extensors provocation exercise consisting of 3 sets of 25 isometric contractions. Contraction intensity level was fixed respectively at 60%, 55% and 50% of previously determined maximal voluntary contraction for the first, second and third sets. This provocation exercise was followed by either an active (AR) recovery (25 min pedaling on a cycle ergometer), an electrostimulated (ESR) recovery (25-min continuous and non-tetanic (5 Hz) stimulation of the quadriceps) or a strictly passive recovery (PR). Peak torques of knee extensors and subjective perception of muscle pain (VAS, 0-10) were evaluated before (pre-ex), immediately after the provocation exercise (post-ex), after the recovery period (post-rec), as well as 75 minutes (1h15) and one day (24h) after the exercise bout. Time course of peak torque was similar among the different recovery modes: ~ 75% of initial values at post-ex, ~ 90% at post-rec and at 1h15. At 24h, peak torque reached a level close to baseline values (PR: 99.1 ± 10.7%, AR: 105.3 ± 12.2%, ESR: 104.4 ± 10.5%). VAS muscle pain scores decreased rapidly between post-ex and post-rec (p < 0.001); there were no significant differences between the three recovery modes (p = 0.64). In conclusion, following a submaximal isometric knee extension exercise, neither electrostimulated nor active recovery strategies significantly improved the time course of muscle function recovery. Key pointsThree sets of submaximal isometric contractions at 60%, 55% and 50% of MVC induced an early fatigue without DOMS but did not lead to exhaustion.In comparison with passive recovery, active and electrostimulated recovery did not lead to significantly higher MVC torques 24h after the exercise bout.No significant differences were demonstrated between the effects of passive, active and electrostimulated recoveries on muscle pain after repeated submaximal isometric contractions.


Methadone for Opioid Use Treatment during Pregnancy: Trends in Postpartum Dose Adjustments.
Objective This study examines methadone dose adjustment postpartum. Methods A retrospective study of women with methadone for opioid use treatment (OUT) during pregnancy was performed. Patient charts were reviewed and data were extracted. Methadone doses from five temporal data points for each patient were used: starting dose, day of delivery, and 1, 2, and 6 months postpartum. Results Over 26 months, 49 pregnancies to women using methadone for OUT were evaluated and 20 (41%) were included. The mean methadone starting dose was 47 mg, compared with 86 mg at the time of delivery. The mean dose postpartum remained unchanged from delivery and 75% of pregnancies required the same dose or higher 1 month postpartum. By 2 months postpartum, only 33% were able to decrease their methadone dose. Twelve pregnancies completed follow-up until 6 months postpartum; only 17% of patients were able to decrease their dose, with an overall mean dose decrease was 12%. There was no difference between the mean dose at delivery and the 6-month postpartum dose. Conclusion Patients using methadone for OUT during pregnancy achieved minimal dose decreases postpartum. Patients should be counseled that postpartum dose tapers may be challenging and about alternatives to methadone for OUT.


Cell killing and division delay in asynchronous and synchronized HeLa cells irradiated with alpha particles or X rays.
HeLa cells irradiated with a single or two split doses of alpha particles or X rays were observed with time-lapse photography or examined for their colony-forming ability. The cell cycle-dependent variation of cell killing and division delay were compared in synchronous and asynchronous cell populations. Cellular damage by alpha particles was manifested in the form of cessation of division, or death, rather than partial division which was predominant for X irradiation. Furthermore, an increased number of interrupted divisions leading to death following split doses correlated with the lack of production of reparable damage from alpha particles. As to the cell cycle-dependent variation of radiosensitivity, a somewhat different pattern was noted with alpha particles, especially for division delay. The pattern of cell killing with alpha particles was similar to that found with X rays, in that high sensitivity was noted at or close to mitosis, while a resistant peak remained at late S but not in early G1. The pattern of division delay was similar for X rays and alpha particles during G2-M, with a maximum delay at mid G2 and no delay past the transition point, but differed during G1-S. During this period, division delay increased with cell age, whereas it showed a broad peak at G1-S boundary and a trough at late S for X rays. There was a reverse correlation between division delay and cell killing except for G2-M in the case of X rays. However, such was not the case for alpha particles.


Melanoma of unknown primary.
Formally described in the 1960s, melanoma of unknown primary (MUP) is characterized by the finding of metastatic melanoma within the lymph nodes, subcutaneous tissues, and other distant sites without an evident primary lesion. The most likely hypothesis of its etiology is an immune-mediated regression of the primary after metastasis has occurred. In addition, patients with MUP appear to have equivalent or better outcomes compared with patients with known primaries of a similar stage.


Adult stem cell-based apexogenesis.
Generally, the dental pulp needs to be removed when it is infected, and root canal therapy (RCT) is usually required in which infected dental pulp is replaced with inorganic materials (paste and gutta percha). This treatment approach ultimately brings about a dead tooth. However, pulp vitality is extremely important to the tooth itself, since it provides nutrition and acts as a biosensor to detect the potential pathogenic stimuli. Despite the reported clinical success rate, RCT-treated teeth are destined to be devitalized, brittle and susceptible to postoperative fracture. Recently, the advances and achievements in the field of stem cell biology and regenerative medicine have inspired novel biological approaches to apexogenesis in young patients suffering from pulpitis or periapical periodontitis. This review mainly focuses on the benchtop and clinical regeneration of root apex mediated by adult stem cells. Moreover, current strategies for infected pulp therapy are also discussed here.


Multi-Frame Star Image Denoising Algorithm Based on Deep Reinforcement Learning and Mixed Poisson-Gaussian Likelihood.
Mixed Poisson-Gaussian noise exists in the star images and is difficult to be effectively suppressed via maximum likelihood estimation (MLE) method due to its complicated likelihood function. In this article, the MLE method is incorporated with a state-of-the-art machine learning algorithm in order to achieve accurate restoration results. By applying the mixed Poisson-Gaussian likelihood function as the reward function of a reinforcement learning algorithm, an agent is able to form the restored image that achieves the maximum value of the complex likelihood function through the Markov Decision Process (MDP). In order to provide the appropriate parameter settings of the denoising model, the key hyperparameters of the model and their influences on denoising results are tested through simulated experiments. The model is then compared with two existing star image denoising methods so as to verify its performance. The experiment results indicate that this algorithm based on reinforcement learning is able to suppress the mixed Poisson-Gaussian noise in the star image more accurately than the traditional MLE method, as well as the method based on the deep convolutional neural network (DCNN).


[The niche for hematopoietic stem and progenitor cells in bone marrow].
It has been hypothesized that the special microenvironments known as niches in the bone marrow play an essential role in maintaining hematopoietic stem and progenitor cells(HSPCs), and the identification of the HSPC niche has been a subject of long-standing argument. Recent studies identified candidate cells meeting the criteria for HSPC niches and the critical transcription factor of their development and maintenance.


The Potential of Cannabinoid-Based Treatments in Tourette Syndrome.
Novel pharmacological treatments are needed for Tourette syndrome. Our goal was to examine the current evidence base and biological rationale for the use of cannabis-derived medications or medications that act on the cannabinoid system in Tourette syndrome. We conducted a comprehensive literature search of PubMed for randomized controlled trials or clinical trials of cannabis-derived medications in Tourette syndrome. Data regarding the population, intervention, safety profile, and outcomes for each trial were extracted and reported and the evidence supporting use of individual cannabis-derived medications was critiqued. There is a strong biological rationale regarding how cannabis-derived medications could affect tic severity. Anecdotal case reports and series have noted that many patients report that their tics improve after using cannabis. However, only two small randomized, placebo-controlled trials of Δ9-tetrahydrocannabinol have been published; these suggested possible benefits of cannabis-derived agents for the treatment of tics. Trials examining other agents active on the cannabinoid system for tic disorders are currently ongoing. Cannabinoid-based treatments are a promising avenue of new research for medications that may help the Tourette syndrome population. However, given the limited research available, the overall efficacy and safety of cannabinoid-based treatments is largely unknown. Further trials are needed to examine dosing, active ingredients, and optimal mode of administration of cannabis-derived compounds, assuming initial trials suggest efficacy. Clinical use for refractory patients should at the very least be restricted to adult populations, given the uncertain efficacy and risk of developmental adverse effects that cannabinoids may have in children. Even in adult populations, cannabis-derived medications are associated with significant issues such as the effects they have on driving safety and the fact that they cause positive urine drug screens that can affect employment.


Corticotropin-Releasing Factor Receptors and Their Interacting Proteins: Functional Consequences.
The corticotropin-releasing factor (CRF) system, which is involved in stress, addiction, and anxiety disorders such as depression, acts through G-protein-coupled receptors (GPCRs) known as type-1 and type-2 CRF receptors. The purpose of this review is to highlight recent advances in the interactions of CRF receptors with other GPCRs and non-GPCR proteins and their associated functional consequences. A better understanding of these interactions may generate new pharmacological alternatives for the treatment of addiction and stress-related disorders.


The long-wavelength limit of the structure factor of amorphous silicon and vitreous silica.
Liquids are in thermal equilibrium and have a non-zero structure factor S(Q --> 0) = [<N(2)>-<N>(2)]/<N> = rho(0)k(B)Tchi(T) in the long-wavelength limit where rho(0) is the number density, T is the temperature, Q is the scattering vector and chi(T) is the isothermal compressibility. The first part of this result involving the number N (or density) fluctuations is a purely geometrical result and does not involve any assumptions about thermal equilibrium or ergodicity, so is obeyed by all materials. From a large computer model of amorphous silicon, local number fluctuations extrapolate to give S(0) = 0.035 +/- 0.001. The same computation on a large model of vitreous silica using only the silicon atoms and rescaling the distances gives S(0) = 0.039 +/- 0.001, which suggests that this numerical result is robust and perhaps similar for all amorphous tetrahedral networks. For vitreous silica, it is found that S(0) = 0.116 +/- 0.003, close to the experimental value of S(0) = 0.0900 +/- 0.0048 obtained recently by small-angle neutron scattering. Further experimental and modeling studies are needed to determine the relationship between the fictive temperature and structure.


Foucault imaging and small-angle electron diffraction in controlled external magnetic fields.
We report a method for acquiring Foucault images and small-angle electron diffraction patterns in external magnetic fields using a conventional transmission electron microscope without any modification. In the electron optical system that we have constructed, external magnetic fields parallel to the optical axis can be controlled using the objective lens pole piece under weak excitation conditions in the Foucault mode and the diffraction mode. We observe two ferromagnetic perovskite-type manganese oxides, La0.7Sr0.3MnO3 (LSMO) and Nd0.5Sr0.5MnO3, in order to visualize magnetic domains and their magnetic responses to external magnetic fields. In rhombohedral-structured LSMO, pinning of magnetic domain walls at crystallographic twin boundaries was found to have a strong influence on the generation of new magnetic domains in external applied magnetic fields.


Identification of candidate genes for drought tolerance in coffee by high-throughput sequencing in the shoot apex of different Coffea arabica cultivars.
Drought is a widespread limiting factor in coffee plants. It affects plant development, fruit production, bean development and consequently beverage quality. Genetic diversity for drought tolerance exists within the coffee genus. However, the molecular mechanisms underlying the adaptation of coffee plants to drought are largely unknown. In this study, we compared the molecular responses to drought in two commercial cultivars (IAPAR59, drought-tolerant and Rubi, drought-susceptible) of Coffea arabica grown in the field under control (irrigation) and drought conditions using the pyrosequencing of RNA extracted from shoot apices and analysing the expression of 38 candidate genes. Pyrosequencing from shoot apices generated a total of 34.7 Mbp and 535,544 reads enabling the identification of 43,087 clusters (41,512 contigs and 1,575 singletons). These data included 17,719 clusters (16,238 contigs and 1,575 singletons) exclusively from 454 sequencing reads, along with 25,368 hybrid clusters assembled with 454 sequences. The comparison of DNA libraries identified new candidate genes (n = 20) presenting differential expression between IAPAR59 and Rubi and/or drought conditions. Their expression was monitored in plagiotropic buds, together with those of other (n = 18) candidates genes. Under drought conditions, up-regulated expression was observed in IAPAR59 but not in Rubi for CaSTK1 (protein kinase), CaSAMT1 (SAM-dependent methyltransferase), CaSLP1 (plant development) and CaMAS1 (ABA biosynthesis). Interestingly, the expression of lipid-transfer protein (nsLTP) genes was also highly up-regulated under drought conditions in IAPAR59. This may have been related to the thicker cuticle observed on the abaxial leaf surface in IAPAR59 compared to Rubi. The full transcriptome assembly of C. arabica, followed by functional annotation, enabled us to identify differentially expressed genes related to drought conditions. Using these data, candidate genes were selected and their differential expression profiles were confirmed by qPCR experiments in plagiotropic buds of IAPAR59 and Rubi under drought conditions. As regards the genes up-regulated under drought conditions, specifically in the drought-tolerant IAPAR59, several corresponded to orphan genes but also to genes coding proteins involved in signal transduction pathways, as well as ABA and lipid metabolism, for example. The identification of these genes should help advance our understanding of the genetic determinism of drought tolerance in coffee.


[Toxicity of atrazine and its metabolite deethylatrazine in Thamnocephalus platyurus and Dugesia gonocephala].
The toxicity of Atrazine and that of its Desethylatrazine metabolite has been defined employing two organisms already tested in our labs the Dugesia gonocephala, belonging to a scissiparous strain coming from the island of Tavolara (Sardinia) and the Thamnocephalus platyurus, crustacean anostracan produced under form of quiescent cysts from Creasel Ltd. (Deinze, Belgium). It has been defined the lethal concentrations at 50% of Atrazine and of Desethylatrazine, of which it has been studied also the report dose-effect in the comparisons of the rectilinear motility. The results highlight that in the comparisons of the T. platyurus Atrazine expounds a toxicity of around three times that of its metabolite; this is not seen with the Planarians that are equally sensitive to both the compounds. The use of these two experimental models for the evaluation of the contamination of bodies of water is shown to be particularly useful given their great sensitivity to pollutants.


Effects of intravenous caffeine on fractional flow reserve measurements in coronary artery disease.
Intravenous adenosine is used to minimise the coronary micro-resistance to achieve maximal hyperaemia along with nitrates for optimal fractional flow reserve (FFR) measurements. We hypothesise that caffeine, being a competitive inhibitor of adenosine, would influence adenosine-mediated FFR readings. Consecutive patients undergoing angiogram and FFR measurements were enrolled after abstaining from caffeine for 24 h. Patients with any contraindications to intravenous adenosine or caffeine were excluded. FFR measurements were taken using nitrates and adenosine pre and post 4 mg/kg intravenous caffeine administration and results were compared. 10 patients were analysed (80% men, age 59.9±9.4, weight 87.5±15.6). Baseline caffeine levels were undetectable in all patients and increased significantly postintravenous caffeine administration (16.4±5.5 μg/mL). Baseline preadenosine FFR values were similar before and after caffeine administration (0.91±0.06 vs 0.91±0.07; p=0.41). Postadenosine FFR readings were 0.79±0.07, which increased non-significantly to 0.82±0.11 postcaffeine (p=0.15). Two significant FFR readings (≤0.8) changed to non-significant after caffeine administration (0.77-0.93 and 0.8-0.91). Caffeine may affect FFR results in some patients. Larger studies are warranted to clarify the extent and magnitude of caffeine/adenosine interaction particularly due to ubiquitous nature of caffeine and increasing importance of FFR in clinical practice.


Canadian paediatric asthma action plans and their correlation with current consensus guidelines.
While written action plans are standard in the treatment and management of asthma, significant variability exists in the content and format among plans. This variability results in inconsistent educational messages that lend themselves to patient confusion and suboptimal health outcomes. To assess the content of Canadian paediatric written action plans for consistency in format, layout, zone-defining symptoms, suggested treatment options and adherence to current Canadian asthma care guidelines. Written action plans were sought from Canadian paediatric hospitals, major teaching hospitals associated with academic centres and three national organizations, for a total of 17 plans. An analysis was performed to assess the similarities and differences among plans. Of all the Canadian paediatric written action plans, 76% were found to consist of three zones and 82% incorporated a traffic light-style design. The plans were divided between symptom-based (59%) and combined symptom- and peak-flow rate approaches (41%). Nominal concordance with the 2012 Canadian Thoracic Society guidelines existed with respect to inhaled corticosteroid and oral corticosteroid therapy. Considerable variability existed among the symptom descriptors that defined each zone. Greater consistency existed among treatment strategies, although the suggested treatment was often difficult to ascertain from the plan templates. Canadian written action plans would be improved by nationally clarifying the symptom descriptors for each zone, adding asthma trigger information to the plans, increasing the emphasis of the common cold as a potential harbinger of worsening asthma symptoms and further incorporating national guideline recommendations.


Educational disadvantage impairs functional recovery after hospitalization in older persons.
To determine whether low educational level is associated with poor functional recovery after hospitalization in older adults. We followed 862 patients (374 with low education, defined as <high school) for 6 months after hospitalization. Poor functional recovery was defined as an Activities of Daily Living score that was lower 6 months after hospitalization than 1 month before hospitalization. People who died were also considered to have poor recovery. Of the 862 participants, 351 (41%) experienced poor functional recovery: 124 died and 227 had declines in activities of daily living. There was a graded, statistically significant relation between level of education and poor functional recovery, regardless of impairment of activities of daily living at baseline. Poor functional recovery was more common in subjects with baseline impairment (50% [147/296]) than in those without baseline impairment (36% [204/566]). Independent predictors of poor functional recovery were low education, cognitive impairment, lack of social support, poor self-rated health, and high comorbidity. Sequential addition of demographic, economic, functional, psychosocial, and clinical factors to low education only modestly affected the association between low education and poor functional recovery. Educational disadvantage impairs functional recovery after hospitalization in older persons.


[The etiology research progress of oculo-auriculo-vertebral spectrum].
Oculo-auriculo-vertebral spectrum (OAVS), also known as Goldenhar syndrome, hemifacial microsomia, oculo-auriculo-vertebral dysplasia and facio-auriculo-vertebral spectrum, is a developmental disorder associated with the first and second branchial arches. Most cases are sporadic, while some familial instances observed suggested that the etiology of OAVS heterogeneous. In this review, we summarize the OAVS epidemiology, classification and mainlyheterogeneous etiology.


Titration of intravenous anesthetics for cardioversion: a comparison of propofol, methohexital, and midazolam.
To compare propofol, methohexital, and midazolam administered as titrated infusions for sedation during electrical cardioversion. A prospective, randomized, single-blind comparative study. Coronary care unit in a military teaching hospital. Thirty adult patients with atrial fibrillation, atrial flutter, or paroxysmal supraventricular tachycardia. Each patient required electrical cardioversion. Patients were randomized to receive one of the three study drugs. Ten patients composed one drug group. Demographic variables were similar between groups. Patients were randomized to receive propofol (10 mg/mL), methohexital (5 mg/mL), or midazolam (0.5 mg/mL) administered at 10 mL/min until the patients failed to follow verbal commands and demonstrated a degradation of the lid response to stimulation. Dose requirements (mean +/- SD) were propofol 1.69 +/- 0.46 mg/kg, methohexital 1.07 +/- 0.34 mg/kg, and midazolam 0.16 +/- 0.06 mg/kg. Hemodynamic assessment at baseline, after induction, after cardioversion, and at recovery demonstrated no difference in mean arterial pressure between the three groups. The time to awakening was significantly prolonged in the group that received midazolam (33 +/- 11 mins, p < .05) as compared with the times of the groups that received propofol (11 +/- 4 mins) and methohexital (9 +/- 3 min). Side-effects were similar between groups, with the exception of an increase in pain on injection with propofol and an increased frequency of confusion in those patients receiving midazolam. Recall of the electrical discharges at one hour after the procedure occurred in two patients in the propofol group. In both cases, there were technical problems which caused the duration of the procedure to extend into the anticipated recovery period. Unit dose costs at our institution for a 70-kg patient are: methohexitol, $3.14 (500-mg bottle); medazolam, $14.88 (5-mg vials x 3); and propofol, $6.60 (200-mg ampule). All three drugs are acceptable choices for use during elective direct-current cardioversion. Titration of the agent results in a total drug dose which is usually less than the typical induction dose. There were no significant differences in the hemodynamic actions of these drugs at any time interval. Both propofol and methohexital proved superior in their ability to provide a more rapid anesthetic onset and recovery as compared with midazolam. Propofol offers the advantage of requiring no premixing or dilution, and it is not a controlled substance, although it does result in more pain on injection.


The relation between polychlorinated biphenyls and population metrics of 4 species of fish from the upper Hudson River, New York, USA.
In the upper Hudson River, New York, USA, fish were exposed to polychlorinated biphenyls (PCBs) from the 1940s to 1977, and PCBs still persist in this environment. Yellow perch (Perca flavescens), brown bullhead (Ameiurus nebulosus), smallmouth bass (Micropterus dolomieu), and largemouth bass (M. salmoides) were collected annually from 2003 to 2009 from 1 control site upstream of the PCB discharge locations and from 2 sites downstream from where PCBs were released. Fish PCB concentrations were estimated, and 3 population metrics were examined: 1) relative abundance, 2) weight-to-length ratio, and 3) growth. Normalized lipid-based PCB concentrations at the 2 PCB exposure pools averaged approximately 100 to 600 μg/g. Estimated relative abundances with electrofishing were higher for largemouth bass, smallmouth bass, and brown bullhead at PCB exposure sites compared to the control site; but yellow perch were more abundant at the control site. Weight to length ratios varied among sites and species, but no consistent pattern was evident in relation to PCBs at the population level or for individual fish. Growth rates for yellow perch and brown bullhead were similar among sites. Largemouth bass growth was slightly higher at the control site compared to the 2 PCB sites, but smallmouth bass growth was much higher at the PCB sites compared to the control site. We could not detect any relation or influence of PCBs on the 3 population metrics that we examined. the present results corroborated those of previous investigations concerning the effects of PCBs on fishes. We recommend stronger consideration of the biological impacts of PCBs at the population level when conducting risk assessments. Environ Toxicol Chem 2019;38:329-339. © 2018 SETAC.


Degradation of curcuminoids by in vitro pure culture fermentation.
Colonic bacteria may mediate the transformation of curcuminoids, but studies of this metabolism are limited. Here, the metabolism of curcuminoids by Escherichia fergusonii (ATCC 35469) and two Escherichia coli strains (ATCC 8739 and DH10B) was examined in modified medium for colon bacteria (mMCB) with or without pig cecal fluid. LC-MS analysis showed that 16-37% of curcumin, 6-16% of demethoxycurcumin (DMC) and 7-15% of bis-demethoxycurcumin (Bis-DMC), and 7-15% of bis-demethoxycurcumin (Bis-DMC) were converted following 36 h of fermentation, with the amount of curcuminoids degraded varying depending on the bacterial strain and medium used. Three metabolites (dihydrocurcumin (DHC), tetrahydrocurcumin (THC), and ferulic acid (FA)) were found in fermentation cultures with all strains used. In addition, a compound with m/z [M - H](-) 470 was found and identified to be a curcumin adduct (curcumin-l-cysteine), using accurate mass FT-ICR-MS. This study provides insights into the bacterial metabolism of curcuminoids.


Adaptive digital filter for the processing of atmospheric lidar signals measured by imaging lidar techniques.
The lidar signal measured by the atmospheric imaging lidar technique is subject to sunlight background noise, dark current noise, and fixed pattern noise (FPN) of the image sensor, etc., which presents quite different characteristics compared to the lidar signal measured by the pulsed lidar technique based on the time-of-flight principle. Enhancing the signal-to-noise ratio (SNR) of the measured lidar signal is of great importance for improving the performance of imaging lidar techniques. By carefully investigating the signal and noise characteristics of the lidar signal measured by a Scheimpflug lidar (SLidar) based on the Scheimpflug imaging principle, we have demonstrated an adaptive digital filter based on the Savitzky-Golay (S-G) filter and the Fourier analysis. The window length of the polynomial of the S-G filter is automatically optimized by iteratively examining the Fourier domain frequency characteristics of the residual signal between the filtered lidar signal and the raw lidar signal. The performance of the adaptive digital filter has been carefully investigated for lidar signals measured by a SLidar system under various atmospheric conditions. It has been found that the optimal window length for near horizontal measurements is concentrated in the region of 90-150, while it varies mainly in the region of 40-100 for slant measurements due to the frequent presence of the peak echoes from clouds, aerosol layers, etc. The promising result has demonstrated great potential for utilizing the proposed adaptive digital filter for the lidar signal processing of imaging lidar techniques in the future.


The interaction of Clostridium perfringens enterotoxin with receptor claudins.
Clostridium perfringens enterotoxin (CPE) has significant medical importance due to its involvement in several common human gastrointestinal diseases. This 35 kDa single polypeptide toxin consists of two domains: a C-terminal domain involved in receptor binding and an N-terminal domain involved in oligomerization, membrane insertion and pore formation. The action of CPE starts with its binding to receptors, which include certain members of the claudin tight junction protein family; bound CPE then forms a series of complexes, one of which is a pore that causes the calcium influx responsible for host cell death. Recent studies have revealed that CPE binding to claudin receptors involves interactions between the C-terminal CPE domain and both the 1st and 2nd extracellular loops (ECL-1 and ECL-2) of claudin receptors. Of particular importance for this binding is the docking of ECL-2 into a pocket present in the C-terminal domain of the toxin. This increased understanding of CPE interactions with claudin receptors is now fostering the development of receptor decoy therapeutics for CPE-mediated gastrointestinal disease, reagents for cancer therapy/diagnoses and enhancers of drug delivery.


Mutations dissociating the inhibitory activity of the pokeweed antiviral protein on eukaryote translation and Escherichia coli growth.
The pokeweed antiviral protein is a ribosome inactivating protein acting on eukaryotic as well as on prokaryotic ribosomes thus is toxic for both cell types. Using the PCR technique to clone the PAP open reading frame, we characterized two cDNAs coding for proteins inhibiting eukaryotic translation process and which are not toxic for Escherichia coli, unlike the wild type protein. The sequence of the two cDNAs showed that the proteins contain only one and two point mutations. This result suggest that the wild type amino acids in the mutated positions participate in the prokaryotic ribosome recognition. These mutants might be useful for the construction of immunotoxins containing the pokeweed antiviral protein as toxin.


The impact of metalloestrogens on the physiology of male reproductive health as a current problem of the XXI century.
In the XXIst century in highly developed countries, progressively decreasing male reproductive potential is indicated. In recent years epidemiological studies indicate the deterioration of semen parameters: reduction of ejaculate volume, sperm count, and mobility, as well as abnormalities in their morphology. Male infertility can result from many different agents, such as: anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies and lifestyle (especially obesity, heat and tobacco smoking). It is well documented that adverse changes in male fertility also seem to be associated with environmental exposure to different substances, especially endocrine active factors, known as xenoestrogens, and among these metal ions, known as metalloestrogens, are very important. The role of some metalloestrogens in various diseases, both in women and men, is known and particularly well-proven in women, but still little is known about their role in the regulation of male reproductive potential. Thus we decided to analyse the available information exploring this problem. The review was carried out using the Medline and Google Scholar databases, using the keywords: xenoestrogens, metalloestrogens, male fertility, semen quality, male reproductive potential, mechanisms of metalloestrogen action, environmental pollution and the name of the particular metal. Articles published between 2000 - 2019 have been taken into account, including human and vertebrate animal studies and cell lines. The aim of this review is to discuss the role and mechanisms of action of fifteen metalloestrogens in the human organism, as well as in animal models, and cell cultures, paying special attention to their influence on the physiology of male reproductive health, according to the current state of knowledge. The role of certain metals in human reproduction is still poorly investigated and for some of them only single studies are available. Many factors in our daily lives have a significant impact on male fertility, therefore education is necessary on the threats and how they may be eliminated as far as possible.


Antiangiogenic-induced hypertension: the molecular basis of signaling network.
Preeclampsia, a pregnancy-related hypertensive disorder, is one of the leading causes of fetal and maternal death globally. Angiogenic factors including vascular endothelial growth factor (VEGF) are involved in the formation of new blood vessels required for placental development and function. The hallmark of preeclampsia is similar to the toxicities related to antiangiogenesis therapy. VEGF inhibitors or antagonists promote vasoconstriction, hypertension and proteinuria. VEGF plays a role in attenuating hypertension and improving kidney damage in an animal model; however, the mechanisms underlying this effect remain poorly defined. The aim of this paper is to summarize recent advances in VEGF-mediated signaling and the target molecules, and provide new insights into treatment strategies for preeclampsia. This article reviews the English-language literature for pathogenesis of preeclampsia based on VEGF signaling and hypertension. VEGF activates downstream signaling molecules, including Ca(2+)/CAMKK, Rac1/NOX, ROS/ERK, Ezrin/Calpain/PI3K/Akt, PLCγ/PKC and Src/HSP90. Among these signalings, important pathways for receptor-triggered intracellular signaling are (1) the PI3K/Akt-dependent, (2) the PLCγ-dependent and (3) the ERK/Egr-1-dependent pathway. VEGF is closely involved in receptor-activated signaling events, leading to eNOS-dependent NO synthesis and eNOS-independent endothelial cell proliferation, respectively, and thus modulates vasoactive function and angiogenic response. This review highlights the potential role of NO in vasodilation, while stress-related ERK activation might act to strengthen angiogenesis, migration and proliferation. We discuss the similarity between preeclampsia and VEGF-targeted therapy-induced hypertension.


pH-Sensitive Micelles Based on Star Copolymer Ad-(PCL-b-PDEAEMA-b-PPEGMA)₄ for Controlled Drug Delivery.
Enhancing drug loading efficacy and stability of polymeric micelles remains a grand challenge. Here we develop adamantane-based star copolymers adamantane-[poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate)]₄ (Ad-(PCL-b-PDEAEMA-b-PPEGMA)₄) and their self-assembled micelles for controlled drug delivery. Results show that the polymers have excellent stability in solution with low critical micelle concentration (CMC) (0.0025⁻0.0034 mg/mL) and the apparent base dissociation constant (pKb) of the polymers is from 5.31 to 6.05. Dynamic light scattering analysis exhibits the great environmental response capability of the pH-sensitive micelles according to particle sizes and zeta potentials. With the synergy effect of the adamantane and hydrophobic block, the micelles display the high Doxorubicin (DOX) loading efficacy (up to 22.4%). The DOX release study shows that the micelles are capable of controlled release for drug. This work indicates the Ad-(PCL-b-PDEAEMA-b-PPEGMA)₄ micelles may provide new guidelines for drug control and release system in overcoming cancer treatment.


Trevor's disease: mimicking anterior ankle impingement syndrome: case report.
This report concerns an unusual cause of anterior ankle impingement. The case of a young male with Trevor's disease mimicking an anterior spur of the ankle that resulted in anterior impingement and treated with ankle arthroscopy is presented. The aim of this study is to explain the different diagnostic properties of Trevor's disease from a classic anterior spur. Level of evidence IV.


Enzymatic phosphorylation of streptomycin by extracts of streptomycin-producing strains of Streptomyces.
Extracts of post-exponential phase mycelia of Streptomyces bikiniensis ATCC 11062, and other streptomycin-producers, catalyze phosphorylation of streptomycin and dihydrostreptomycin with adenosine-5'-triphosphate. The phosphate is esterified with an -OH group of the streptidine moiety. It is suggested that O-phosphoryl-streptomycin might serve as an intracellular precursor of extracellular streptomycin or as a detoxification product of streptomycin or that it might serve an unknown physiological function in the producing organism.


All-Inorganic Luminescent Ternary Cadmium Halide Cs7Cd3Br13 with Two Types of Cd-Centered Polyhedrons.
All-inorganic metal halides comprise a class of semiconductor material with a wide range of applications. In these materials, cadmium-related materials have excellent optical properties in the field of binary quantum dots. However, ternary cadmium halides have not attracted much attention until now. Here, we successfully synthesize a ternary all-inorganic cesium cadmium bromide, Cs7Cd3Br13, and obtained its acicular single crystals through a simple solvent evaporation method. Cadmium atoms are found to be coordinated with bromine atoms in two different polyhedrons including isolated [CdBr4]2- tetrahedrons and corner-shared [CdBr6]4- octahedral chains in the unit cells of Cs7Cd3Br13. Optical properties are then measured and the needlelike single crystals are found to have an orange emission at 630 nm upon 365 nm UV light with a photoluminescence quantum yield (PLQY) of 9.85%. The orange luminescence with large Stokes shift (255 nm) and broad full width at half-maximum (fwhm = 147 nm) is derived from self-trapped excitons, and it is further evidenced by temperature-variable photoluminescence spectra. The PL decay spectrum shows the lifetime of Cs7Cd3Br13 is 1.26 μs. Finally, DFT calculation reveals that Cs7Cd3Br13 has a direct band gap with a value of 3.09 eV.


[Neurotransmitters and modulators in the cerebellum].
It is well-known that anatomically, the cerebellum has a very uniform and stereotyped structure with geometrical precision. The Purkinje cell, which provides the unique output from the cerebellum, receives two excitatory inputs: one is from parallel fibers, axons of the granule cells, and the other is from climbing fibers which originate at the inferior live. In order to characterize the neurotransmitter of the climbing fibers, the electrophysiological properties of Purkinje cells were first studied by intradendritic as well as intrasomatic recordings from Purkinje cells of guinea pig cerebellar slices. Comparison of the reversal properties, ionic dependency and the sensitivity to various antagonists of the climbing fiber responses with those of responses to L-glutamate and L-aspartate supports the previous suggestion based on the bio- and histochemical observations that L-aspartate is more likely than L-glutamate to be the neurotransmitter of the climbing fiber synapses. The Purkinje cell is also reported to contain a relatively high activity of NADP-linked prostaglandin (PG)D2 dehydrogenase and abundant PGD2 binding sites. PGs potentiate the actions of both excitatory and inhibitory neurotransmitter candidates in our experimental system. In this article, the role of prostaglandins in the neuronal transmission in the cerebellum is also described.


Effect of silver nanoparticles on gene transcription of land snail Helix aspersa.
Silver nanoparticles (Ag-NPs) are extremely useful in a diverse range of consumer goods. However, their impact on the environment is still under research, especially regarding the mechanisms involved in their effect. Aiming to provide some insight, the present work analyzes the transcriptional activity of six genes (Hsp83, Hsp17.2, Hsp19.8, SOD Cu-Zn, Mn-SOD, and BPI) in the terrestrial snail Helix aspersa in the presence of different concentrations of Ag-NPs. The animals were exposed for seven days to Lactuca sativa soaked for one hour in different concentrations of Ag-NPs (20, 50, 100 mg/L). The results revealed that the highest concentration tested of Ag-NPs (100 mg/L) led to a statistically significant induction of the Hsp83 and BPI expression in the digestive gland compared to the control group. However, a trend to upregulation with no statistical significance was observed for all the genes in the digestive gland and the foot, while in the hemolymph, the trend was to downregulation. Ag-NPs affected the stress response and immunity under the tested conditions, although the impact was weak. It is necessary to explore longer exposure times to confirm that the effect can be maintained and impact on health. Our results highlight the usefulness of the terrestrial snail Helix aspersa as a bioindicator organism for silver nanoparticle pollution biomonitoring and, in particular, the use of molecular biomarkers of pollutant effect as candidates to be included in a multi-biomarker strategy.


Cataract development in sand and galactosemic rats fed a natural tomato extract.
This study investigated the effect of a natural tomato extract (TE) on cataract formation in two animal models. A TE containing 5% lycopene was included in the diet of diabetic sand rats at 0.2%, and Sprague Dawley rats were fed a high-galactose diet (30 g/100 g of diet), supplemented with either the lycopene-rich extract at concentrations of 0.2, 0.4, and 0.8% or BHT (0.2%). TE had no significant effect on plasma glucose levels or cataract development in sand rats; however, in rats maintained on a diet rich in galactose, both BHT and TE decreased cataract incidence, and grades were lower than in control animals. In addition, lens protein and reduced glutathione levels were higher and aldose reductase activity was lower than in the control group. The results suggest that antioxidants act as protective agents when oxidative stress is a primary cause of cataract formation but may be less effective in preventing cataracts in hyperglycemic animals.


[Preparation of carbon nanoparticle paclitaxel suspension and pharmacokinetic study of intraperitoneal chemotherapy].
To prepare carbon nanoparticle-paclitaxel suspension(CNPS) and to study the pharmacokinetics of intraperitoneal chemotherapy with CNPS. Saturated absorption capacity of carbon nanoparticle suspension (CNS) and paclitaxel were detected by high performance liquid chromatography in order to prepare the above suspension. Wistar rats were randomly divided into the experimental group (A) and the control group (B), to which intraperitoneal injections of CNPS and paclitaxel were given respectively. At different time points, measure the blood samples, mesenteric lymph nodes, and intraperitoneal lavage fluid were collected to measure the concentration of paclitaxel. One ml CNS could absorb 7 mg paclitaxel by maximum. The ratio of area under the curve (AUC) in the plasma of group A to group B was 0.63. The ratio of AUC in lymph nodes of group A to group B was 0.75 and that in intraperitoneal lavage fluid was 1.25. The metabolic half-life (t1/2) of paclitaxel in the plasma of group A was 1.61 times as long as that of group B. The t1/2 of paclitaxel in intraperitoneal lavage fluid of group A was 0.88 as long as that of Group B. The t1/2 of paclitaxel in lymph nodes of group A was 1.10 as long as that of Group B. CNS has a high absorption capacity with paclitaxel. Intraperitoneal chemotherapy by CNPS is characterized by low drug concentration in the blood, high drug concentration in the peritoneal cavity and high safety. However, the targeting and lymphatic retention effect are not significant. The mechanism warrants further investigation.


Islam and Mental Disorders of the Older Adults: Religious Text, Belief System and Caregiving Practices.
This paper illustrates the impact of Islamic religious texts on dementia care in the Middle East. It examines how old age and older adults mental disorders are framed in the Quran and Hadith, and how these texts are transformed to belief ideologies and caregiving practices. The study uses a qualitative research methods, which include a review of all Islamic holy texts that address mental and cognitive changes associated with ageing, along with interviews with eight Sharia scholars and 37-Arab-Muslim families living in Qatar. Islamic texts command compassion and honouring of elderly parents and give care instructions. These texts are transformed into social practices and used as diagnostic and treatment tools.


[Close-of-the-century trends in Mexican urbanization].
"This article reviews the main characteristics of Mexican urban development during the eighties through the study of its spatial-demographic aspects and the changes in the space-sector structure of [the] economy, and suggests a prospect of national urbanization for the nineties.... The main point is to illustrate and explain why the eighties can be considered a milestone in urban development, [introducing] a new trend in Mexican urbanization which will consolidate during the nineties." (SUMMARY IN ENG)


A retrospective study of 21 cases of malignant odontogenic tumours from two tertiary health centres in Nigeria.
Malignant odontogenic tumours (MOTs) are relatively rare tumours and only few cases have been reported in the sub-Sahara African literature. The aim of this study was to describe the demographic distribution of malignant odontogenic tumours in two tertiary health centres based on the current WHO 2005 classification scheme. We reviewed 21 malignant odontogenic tumours out of a total of 374 odontogenic tumours from two Tertiary Health Centres. Information regarding histology, location, patients age and gender for MOTs were analysed using SPSS for Windows (version 20.0; SPSS Inc. Chicago, IL). Twenty one (5.6%) MOTs out of a total of 374 odontogenic tumours were seen from the two institutions over the study period. The median age for MOTs was 42.0 (± 19.0) years (range = 16-66 years). The male: female ratio was 2.5:1 and 85.7% occurred in the mandible. Ameloblastic carcinoma (AC) with 13 (61.9%) cases was the most common MOT. AC had a mean age of 37.5 (± 11.9) years. AC had a mandible: maxilla ratio of 5.5:1 with majority (84.6%) occurring in the posterior mandible. This study showed that MOTs are rare lesions. AC was the most common MOT and majority of MOTs occurred in the posterior mandible of male patients. The study helps to better elucidate the demography of MOTs in sub-Sahara Africans.


Incontinentia Pigmenti presenting as a newborn eruption: two case presentations.
Linear vesicles or papules in a newborn can be a presenting sign of incontinentia pigmenti (IP). In this report, we present two cases of neonates with cutaneous manifestations of incontinentia pigmenti. In one case, mild peripheral eosinophilia was noted. No extra-cutaneous manifestations were noted otherwise in both cases after complete ophthalmological and neurological evaluations. These cases serve as a reminder for clinicians to consider IP in newborns presenting with linear vesicles or papules.


Hybridization underlies localized trait evolution in cavefish.
Introgressive hybridization may play an integral role in local adaptation and speciation (Taylor and Larson, 2019). In the Mexican tetra Astyanax mexicanus, cave populations have repeatedly evolved traits including eye loss, sleep loss, and albinism. Of the 30 caves inhabited by A. mexicanus, Chica cave is unique because it contains multiple pools inhabited by putative hybrids between surface and cave populations (Mitchell et al., 1977), providing an opportunity to investigate the impact of hybridization on complex trait evolution. We show that hybridization between cave and surface populations may contribute to localized variation in traits associated with cave evolution, including pigmentation, eye development, and sleep. We also uncover an example of convergent evolution in a circadian clock gene in multiple cavefish lineages and burrowing mammals, suggesting a shared genetic mechanism underlying circadian disruption in subterranean vertebrates. Our results provide insight into the role of hybridization in facilitating phenotypic evolution.


Growth slowdown and arrest lines.
Transversely oriented lines within the metaphyses and proximate diaphyses were studied in multiple specimens from cadavers and amputation specimens from skeletally immature individuals. These lines, evident as transverse trabecular bands of increased radiodensity, proved histologically to be thickened, transversely interconnected trabecular networks, with more typical, longitudinally oriented trabecular bone on either side. They appeared following a temporary slowdown or cessation of rapid longitudinal bone formation in the primary spongiosa and were parallel to the contours of the contiguous physis. When growth rates were normal, longitudinally oriented trabeculae with interspersed marrow elements predominated at the zone of transformation of cartilage to bone. However, when growth rates slowed down or were temporarily arrested, the trabeculae thickened and fused with each other transversely. When the abnormal process (e.g., fracture or systemic illness) responsible for growth retardation subsided, more rapid rates of endochondral growth and transformation resumed, forming the more characteristic normal longitudinal trabecular orientation. As the bone elongated, these transverse lines were progressively displaced from the physis. As the metaphyseal bone was remodeled to diaphyseal bone, these trabecular lines were gradually remodeled and usually disappeared completely by the time skeletal maturity was reached.


Nanodiamond uptake in colon cancer cells: the influence of direction and trypsin-EDTA treatment.
Nanoparticles are routinely used in cell biology. They deliver drugs or function as labels or sensors. For many of these applications it is essential that the nanoparticles enter the cells. While some cell types readily ingest all kinds of particles, others just don't. We report that uptake can be enhanced for some cells if the particles are administered from the basolateral side of the cells (in this case from below). Compared to apical uptake (from above), we report an 8-fold increase in the number of fluorescent nanodiamonds internalized by the colon cancer cell line HT29. Up to 96% of the cells treated by a modified protocol contain at least one nanodiamond, whereas in the control group we could observe nanodiamonds in less than half of the cells. We were also able to show that simple treatment of cell clusters with trypsin-EDTA leads to the same enhancement of the nanodiamond uptake as seeding the cells on top of the nanoparticles. Although our study is focused on nanodiamonds in HT29 cells, we believe that this method could also be applicable for other nanoparticles and cells with a specific directionality.


The vtc4 gene influences polyphosphate storage, morphogenesis, and virulence in the maize pathogen Ustilago maydis.
The maize pathogen Ustilago maydis switches from budding to filamentous, dikaryotic growth in response to environmental signals including nutrient status, growth in the host, and the presence of mating pheromones. The filamentous dikaryon is capable of proliferating within host tissue to cause disease symptoms including tumors. The transition from yeast cells to hyphal filaments is regulated by a mitogen-activated protein kinase cascade and a cyclic-AMP-protein kinase A (PKA) pathway. Serial analysis of gene expression with PKA mutants identified orthologs of components of the PHO phosphate acquisition pathway as transcriptional targets of the PKA pathway, and these included genes for Pho84, an acid phosphatase, and the vacuolar transport chaperones Vtc1 and Vtc4. In Saccharomyces cerevisiae, Vtc4p is required during the fusion of inorganic-phosphate-containing vesicles to the vacuolar membrane and the consequent accumulation of phosphate stored as polyphosphate (polyP) in the vacuole. We found that deletion of vtc4 in U. maydis also reduced polyP stored in vacuoles. Intriguingly, Deltavtc4 mutants possessed a filamentous cellular morphology, in contrast to the budding, yeast-like growth of the wild-type parent. The Deltavtc4 mutants also displayed decreased symptom development and reduced proliferation in planta. The interaction with PKA signaling was further investigated by the generation of Deltavtc4 ubc1 double mutants. Deletion of vtc4 completely suppressed the multiple-budded phenotype of a Deltaubc1 mutant, indicating that polyP stores are essential for this PKA-induced trait. Overall, this study reveals a novel role for PKA-regulated polyP accumulation in the control of fungal morphogenesis and virulence.