Self-guided propagation of ultrashort laser pulses in the anomalous dispersion region of transparent solids: a new regime of filamentation.
We report measurements concerning the propagation of femtosecond laser pulses in fused silica with a wavelength at 1.9 μm falling in the negative group velocity dispersion region. Under sub-GW excitation power, stable filaments are observed over several cm showing the emergence of nonspreading pulses both in space and time. At higher excitation powers, one observes first multiple pulse splitting followed by the emergence of the quasispatiotemporal solitary filament. These results are well reproduced by numerical simulations.


Significance of reservoir length in the endorectal ileal pullthrough with ileal reservoir.
Ileal reservoirs have been used almost routinely in conjunction with total colectomy and the endorectal ileal pullthrough procedure for ulcerative colitis and familial polyposis. Of 153 patients who underwent surgery at UCLA Medical Center during the past seven years, a comparison was made between 14 patients with an initial reservoir length of greater than 30 cm (large) and 54 patients with a short reservoir (14 to 20 cm). Although patients with long reservoirs had a low stool frequency in the first postoperative year, there was a subsequent increase. During the first two postoperative years, six (43%) of 14 patients developed reservoir enlargement with secondary pouchitis and diarrhea, which severely limited their activities, finally requiring partial resection. Only one of the 14 patients with short reservoirs who underwent surgery more than two years previously had a resection. Complications requiring operative treatment were more than five times greater in patients with long reservoirs. All patients with shortened reservoirs experienced dramatic improvement in their clinical course within one month. Ileal reservoirs of 14 to 16 cm in length appear to provide long-term, excellent clinical function, with an incidence of pouchitis of less than 5%. Symptoms in patients with large reservoirs may be greatly improved by reservoir shortening.


Sampling Performance of Multiple Independent Molecular Dynamics Simulations of an RNA Aptamer.
Using multiple independent simulations instead of one long simulation has been shown to improve the sampling performance attained with the molecular dynamics (MD) simulation method. However, it is generally not known how long each independent simulation should be, how many independent simulations should be used, or to what extent either of these factors affects the overall sampling performance achieved for a given system. The goal of the present study was to assess the sampling performance of multiple independent MD simulations, where each independent simulation begins from a different initial molecular conformation. For this purpose, we used an RNA aptamer that is 25 nucleotides long as a case study. The initial conformations of the aptamer are derived from six de novo predicted 3D structures. Each of the six de novo predicted structures is energy minimized in solution and equilibrated with MD simulations at high temperature. Ten conformations from these six high-temperature equilibration runs are selected as initial conformations for further simulations at ambient temperature. In total, we conducted 60 independent MD simulations, each with a duration of 100 ns, to study the conformation and dynamics of the aptamer. For each group of 10 independent simulations that originated from a particular de novo predicted structure, we evaluated the potential energy distribution of the RNA and used recurrence quantification analysis to examine the sampling of RNA conformational transitions. To assess the impact of starting from different de novo predicted structures, we computed the density of structure projection on principal components to compare the regions sampled by the different groups of ten independent simulations. The recurrence rate and dependence of initial conformation among the groups were also compared. We stress the necessity of using different initial configurations as simulation starting points by showing long simulations from different initial structures suffer from being trapped in different states. Finally, we summarized the sampling efficiency for the complete set of 60 independent simulations and determined regions of under-sampling on the potential energy landscape. The results suggest that conducting multiple independent simulations using a diverse set of de novo predicted structures is a promising approach to achieve sufficient sampling. This approach avoids undesirable outcomes, such as the problem of the RNA aptamer being trapped in a local minimum. For others wishing to conduct multiple independent simulations, the analysis protocol presented in this study is a guide for examining overall sampling and determining if more simulations are necessary for sufficient sampling.


Serum cholesterol levels and the risk of multiple system atrophy: a case-control study.
Cholesterol in brain membranes may modulate the conformational state and accumulation of alpha-synuclein in alpha-synucleinopathies.We examined the association between serum cholesterol and the risk of multiple system atrophy (MSA), one of the alpha-synucleinopathies. We enrolled 142 patients with probable MSA from two tertiary referral hospitals and 155 age- and gender-matched healthy people with no neurological disease. The levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were significantly lower in MSA patients than in controls (total cholesterol: 172.7 vs. 196.3 mg/dL, P < 0.001; LDL-C: 104.0 vs. 115.3 mg/dL, P = 0.001; HDL-C: 47.3 vs. 54.2 mg/dL, P < 0.001). After adjusting for age, gender, use of cholesterol-lowering drugs, and histories of hypertension, diabetes mellitus, and smoking, the odds ratios was 5.9 (95% CI = 2.3-11.5, P < 0.001) for MSA patients in the lowest quartile of total cholesterol and 2.6 (95% CI = 1.2-5.5, P = 0.016) for those in the lowest quartile of HDL-C, compared with the highest quartiles. Levels of serum cholesterol did not significantly correlate with disease duration or severity. Our data suggest that lower levels of total cholesterol and HDL may be associated with an increased risk of MSA.


Cost-effectiveness of an HPV self-collection campaign in Uganda: comparing models for delivery of cervical cancer screening in a low-income setting.
With the availability of a low-cost HPV DNA test that can be administered by either a healthcare provider or a woman herself, programme planners require information on the costs and cost-effectiveness of implementing cervical cancer screening programmes in low-resource settings under different models of healthcare delivery. Using data from the START-UP demonstration project and a micro-costing approach, we estimated the health and economic impact of once-in-a-lifetime HPV self-collection campaign relative to clinic-based provider-collection of HPV specimens in Uganda. We used an individual-based Monte Carlo simulation model of the natural history of HPV and cervical cancer to estimate lifetime health and economic outcomes associated with screening with HPV DNA testing once in a lifetime (clinic-based provider-collection vs a self-collection campaign). Test performance and cost data were obtained from the START-UP demonstration project using a micro-costing approach. Model outcomes included lifetime risk of cervical cancer, total lifetime costs (in 2011 international dollars [I$]), and life expectancy. Cost-effectiveness ratios were expressed using incremental cost-effectiveness ratios (ICERs). When both strategies achieved 75% population coverage, ICERs were below Uganda's per capita GDP (self-collection: I$80 per year of life saved [YLS]; provider-collection: I$120 per YLS). When the self-collection campaign achieved coverage gains of 15-20%, it was more effective than provider-collection, and had a lower ICER unless coverage with both strategies was 50% or less. Findings were sensitive to cryotherapy compliance among screen-positive women and relative HPV test performance. The primary limitation of this analysis is that self-collection costs are based on a hypothetical campaign but are based on unit costs from Uganda. Once-in-a-lifetime screening with HPV self-collection may be very cost-effective and reduce cervical cancer risk by > 20% if coverage is high. Demonstration projects will be needed to confirm the validity of our logistical, costing and compliance assumptions.


Pulmonary Function in HIV-Infected Recreational Drug Users in the Era of Anti-Retroviral Therapy.
Individuals with HIV infection commonly have pulmonary function abnormalities, including airflow obstruction and diffusion impairment, which may be more prevalent among recreational drug users. To date, the relationship between drug use and pulmonary function abnormalities among those with HIV remains unclear. To determine associations between recreational drug use and airflow obstruction, diffusion impairment, and radiographic emphysema in men and women with HIV. Cross-sectional analysis of pulmonary function and self-reported recreational drug use data from a cohort of 121 men and 63 women with HIV. Primary outcomes were the presence (yes/no) of: 1) airflow obstruction, (pre- or post-bronchodilator forced expiratory volume in 1 second/forced vital capacity<0.70); 2) moderate diffusion impairment (diffusing capacity for carbon monoxide <60% predicted); and 3) radiographic emphysema (>1% of lung voxels <-950 Hounsfield units). Exposures of interest were frequency of recreational drug use, recent (since last study visit) drug use, and any lifetime drug use. We used logistic regression to determine associations between recreational drug use and the primary outcomes. HIV-infected men and women reported recent recreational drug use at 56.0% and 31.0% of their study visits, respectively, and 48.8% of men and 39.7% of women reported drug use since their last study visit. Drug use was not associated with airway obstruction or radiographic emphysema in men or women. Recent crack cocaine use was independently associated with moderate diffusion impairment in women (odds ratio 17.6; 95% confidence interval 1.3-249.6, p=0.03). In this cross-sectional analysis, we found that recreational drug use was common among HIV-infected men and women and recent crack cocaine use was associated with moderate diffusion impairment in women. Given the increasing prevalence of HIV infection, any relationship between drug use and prevalence or severity of chronic pulmonary diseases could have a significant impact on HIV and chronic disease management.


Phosphorylation of the 27-kDa heat shock protein via p38 MAP kinase and MAPKAP kinase in smooth muscle.
The 27-kDa heat shock protein (HSP27) is expressed in a variety of tissues in the absence of stress and is thought to regulate actin filament dynamics, possibly by a phosphorylation/dephosphorylation mechanism. HSP27 has also been suggested to be involved in contraction of intestinal smooth muscle. We have investigated phosphorylation of HSP27 in airway smooth muscle in response to the muscarinic agonist carbachol. Carbachol increased 32P incorporation into canine tracheal HSP27 and induced a shift in the distribution of charge isoforms on two-dimensional gels to more acidic, phosphorylated forms. The canine HSP27 amino acid sequence includes three serine residues corresponding to sites in human HSP27 known to be phosphorylated by mitogen-activated protein kinase-activated protein (MAPKAP) kinase-2. To determine whether muscarinic receptors are coupled to a "stress response" pathway in smooth muscle culminating in phosphorylation of HSP27, we assayed MAPKAP kinase-2 activity and tyrosine phosphorylation of p38 mitogen-activated protein (MAP) kinase, the enzyme thought to activate MAPKAP kinase-2. Recombinant canine HSP27 expressed in Escherichia coli was a substrate for MAPKAP kinase-2 in vitro as well as a substrate for endogenous smooth muscle HSP27 kinase, which was activated by carbachol. Carbachol also increased tyrosine phosphorylation of p38 MAP kinase. SB-203580, an inhibitor of p38 MAP kinases, reduced activation of endogenous HSP27 kinase activity and blocked the shift in HSP27 charge isoforms to acidic forms. We suggest that HSP27 in airway smooth muscle, in addition to being a stress response protein, is phosphorylated by a receptor-initiated signaling cascade involving muscarinic receptors, tyrosine phosphorylation of p38 MAP kinase, and activation of MAPKAP kinase-2.


COPD Underdiagnosis and Misdiagnosis in a High-Risk Primary Care Population in Four Latin American Countries. A Key to Enhance Disease Diagnosis: The PUMA Study.
Acknowledgement of COPD underdiagnosis and misdiagnosis in primary care can contribute to improved disease diagnosis. PUMA is an international primary care study in Argentina, Colombia, Venezuela and Uruguay. To assess COPD underdiagnosis and misdiagnosis in primary care and identify factors associated with COPD underdiagnosis in this setting. COPD was defined as post-bronchodilator (post-BD) forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <0.70 and the lower limit of normal (LLN). Prior diagnosis was self-reported physician diagnosis of emphysema, chronic bronchitis, or COPD. Those patients with spirometric COPD were considered to have correct prior diagnosis, while those without spirometric criteria had misdiagnosis. Individuals with spirometric criteria without previous diagnosis were considered as underdiagnosed. 1,743 patients were interviewed, 1,540 completed spirometry, 309 (post-BD FEV1/FVC <0.70) and 226 (LLN) had COPD. Underdiagnosis using post-BD FEV1/FVC <0.70 was 77% and 73% by LLN. Overall, 102 patients had a prior COPD diagnosis, 71/102 patients (69.6%) had a prior correct diagnosis and 31/102 (30.4%) had a misdiagnosis defined by post-BD FEV1/FVC ≥0.70. Underdiagnosis was associated with higher body mass index (≥30 kg/m2), milder airway obstruction (GOLD I-II), black skin color, absence of dyspnea, wheezing, no history of exacerbations or hospitalizations in the past-year. Those not visiting a doctor in the last year or only visiting a GP had more risk of underdiagnosis. COPD underdiagnosis (65.8%) and misdiagnosis (26.4%) were less prevalent in those with previous spirometry. COPD underdiagnosis is a major problem in primary care. Availability of spirometry should be a priority in this setting.


Transformation of odor selectivity from projection neurons to single mushroom body neurons mapped with dual-color calcium imaging.
Although the response properties of most neurons are, to a large extent, determined by the presynaptic inputs that they receive, comprehensive functional characterization of the presynaptic inputs of a single neuron remains elusive. Toward this goal, we introduce a dual-color calcium imaging approach that simultaneously monitors the responses of a single postsynaptic neuron together with its presynaptic axon terminal inputs in vivo. As a model system, we applied the strategy to the feed-forward connections from the projection neurons (PNs) to the Kenyon cells (KCs) in the mushroom body of Drosophila and functionally mapped essentially all PN inputs for some of the KCs. We found that the output of single KCs could be well predicted by a linear summation of the PN input signals, indicating that excitatory PN inputs play the major role in generating odor-selective responses in KCs. When odors failed to activate KC output, local calcium transients restricted to individual postsynaptic sites could be observed in the KC dendrites. The response amplitudes of the local transients often correlated linearly with the presynaptic response amplitudes, allowing direct assay of the strength of single synaptic sites. Furthermore, we found a scaling relationship between the total number of PN terminals that a single KC received and the average synaptic strength of these PN-KC synapses. Our strategy provides a unique perspective on the process of information transmission and integration in a model neural circuit and may be broadly applicable for the study of the origin of neuronal response properties.


Biopersistence of rock wool in lungs after short-term inhalation in rats.
To evaluate the safety of rock wool (RW), an asbestos substitute, we examined the biopersistence of RW fibers in rat lungs based on the changes of fiber number and fiber size (length and diameter) by a nose-only inhalation exposure study. Twenty-four male Fischer 344 rats were exposed to RW fibers at a concentration of 30 mg/m(3) continuously for 3 h daily for 5 consecutive days. Six rats each were sacrificed shortly and at 1, 2, and 4 wk after exposure, and their lung tissues were ashed by a low-temperature plasma asher. Then the fiber numbers and fiber sizes in lungs were determined using a phase-contrast microscope and computed image analyzer. During the study period, the arithmetic mean (SD) values of fiber and weight concentrations were 78.5 (35.7) fibers/cm(3), and 29.9 (28.3) mg/m(3), respectively. The fiber number in lungs 4 wk after exposure significantly decreased from the baseline value (shortly after exposure) (p < .05). The half-life of fibers calculated from the approximate curve was 28 days for all fibers and 16 days for fibers with L > 20 microm, and the rate of decrease in fiber number was 46.3% at 4 wk after exposure (shortly-after group = 100%). Likewise, both length and diameter significantly decreased at 4 wk after exposure (p < .05), probably because fibers were phagosytosed and digested by alveolar macrophages, discharged to outside of the body by mucociliary movement, or dissolved by body fluid. It will be necessary in the future to further confirm the safety of RW fibers by assessing the biopersistence of fibers in the lungs and their pathological effects in our ongoing study performed in accordance with the guidelines established in the "Methods for Determination of Hazardous Properties for Human Health of Man Made Mineral Fibers" (EC protocol).


Determinants of diabetes and hypertension control in ambulatory healthcare in Al ain, United arab emirates.
This study aims to study determinants for the control of diabetes and hypertension in Al Ain Ambulatory Healthcare patients. This is a cross sectional observational study of patients attending ambulatory healthcare centers in Al Ain, United Arab Emirates in 2009. From a yearly audit evaluating the care of patients with diabetes and hypertension, the determinants for improved diabetes and hypertension outcomes were identified from a total of 512 patients and its association with glycemic and blood pressure control were studied. From all variables studied, only the clinic where the patient was treated helped predict both improved blood sugar and blood pressure control. For patients with diabetes, poor control the year before (p<0.001), the number of chronic disease clinic visits (p=0.042) and triglyceride levels (p=0.007) predicted worse control of diabetes. A predictor of poor control of blood pressure (p<0.001) for patients with hypertension was poor control of blood pressure in the year before. In this population, the healthcare system and the team played major roles as determinants in the control of patient's diabetes and blood pressure more than any of the other factors examined.


Flexible C6BN Monolayers As Promising Anode Materials for High-Performance K-Ion Batteries.
K-ion batteries attract extensive attention and research efforts because of the high energy density, low cost, and high abundance of K. Although they are considered suitable alternatives to Li-ion batteries, the absence of high-performance electrode materials is a major obstacle to implementation. On the basis of density functional theory, we systematically study the feasibility of a recently synthesized C6BN monolayer as anode material for K-ion batteries. The specific capacity is calculated to be 553 mAh/g (K2C6BN), i.e., about twice that of graphite. The C6BN monolayer is characterized by high strength (in-plane stiffness of 309 N/m), excellent flexibility (bending strength of 1.30 eV), low output voltage (average open circuit voltage of 0.16 V), and excellent rate performance (diffusion barrier of 0.09 eV). We also propose two new C6BN monolayers. One has a slightly higher total energy (0.10 eV) than the synthesized C6BN monolayer, exhibiting enhanced electronic properties and affinity to K. The other is even energetically favorable due to B-N bonding. All three C6BN monolayers show good dynamical, thermal, and mechanical stabilities. We demonstrate excellent cyclability and improved conductivity by K adsorption, suggesting great potential in flexible energy-storage devices.


ATP-binding cassette transporter A1 expression and apolipoprotein A-I binding are impaired in intima-type arterial smooth muscle cells.
Accumulation of excess cholesterol by intimal arterial smooth muscle cells (SMCs) contributes to the formation of foam cells in atherosclerotic lesions. The purpose of this study was to examine the expression and activity of ATP-binding cassette transporter A1 (ABCA1) in model intimal and medial arterial SMCs, in human atherosclerotic coronary artery intimal and medial layers, and in human intimal and medial SMCs. Model intimal arterial SMCs showed increased cholesteryl ester accumulation, absence of apolipoprotein A-I-mediated lipid efflux, markedly diminished ABCA1 expression, and poor apoA-I binding compared with medial-layer SMCs. Total ABCA1 mRNA and SMC-specific ABCA1 protein levels were diminished in the intimal layer compared with the medial layer of atherosclerotic human coronary arteries. Increased expression of ABCA1 by liver X receptor agonist treatment or gene transfection failed to correct apolipoprotein A-I binding, lipid efflux, or high-density lipoprotein particle formation by intima-type SMCs. In addition to impaired ABCA1 expression, intima-type SMCs appear to lack a critical binding factor or factors required for the apolipoprotein A-I-ABCA1 interaction, cholesterol efflux, and high-density lipoprotein particle formation. ABCA1 expression is reduced in cultured model intimal and human atherosclerotic lesion SMCs, suggesting that reduced ABCA1 activity contributes to smooth muscle foam cell formation in the intima.


Temperature representation in the Drosophila brain.
In Drosophila, rapid temperature changes are detected at the periphery by dedicated receptors forming a simple sensory map for hot and cold in the brain. However, flies show a host of complex innate and learned responses to temperature, indicating that they are able to extract a range of information from this simple input. Here we define the anatomical and physiological repertoire for temperature representation in the Drosophila brain. First, we use a photolabelling strategy to trace the connections that relay peripheral thermosensory information to higher brain centres, and show that they largely converge onto three target regions: the mushroom body, the lateral horn (both of which are well known centres for sensory processing) and the posterior lateral protocerebrum, a region we now define as a major site of thermosensory representation. Next, using in vivo calcium imaging, we describe the thermosensory projection neurons selectively activated by hot or cold stimuli. Fast-adapting neurons display transient ON and OFF responses and track rapid temperature shifts remarkably well, while slow-adapting cell responses better reflect the magnitude of simple thermal changes. Unexpectedly, we also find a population of broadly tuned cells that respond to both heating and cooling, and show that they are required for normal behavioural avoidance of both hot and cold in a simple two-choice temperature preference assay. Taken together, our results uncover a coordinated ensemble of neural responses to temperature in the Drosophila brain, demonstrate that a broadly tuned thermal line contributes to rapid avoidance behaviour, and illustrate how stimulus quality, temporal structure, and intensity can be extracted from a simple glomerular map at a single synaptic station.


[Ependymoma with cervical lymph node metastases].
The authors report a case of an ependymoma in which metastases in cervical lymph nodes appeared four and a half years after diagnosis and operation. The primary tumor, an ependymoma grade I (WHO) in the left occipital region, had been completely resected and irradiated. Beside metastases in the cervical lymph nodes, several recurrences in the primary region and multiple metastases to the spinal canal had occurred.


TASIC: determining branching models from time series single cell data.
Single cell RNA-Seq analysis holds great promise for elucidating the networks and pathways controlling cellular differentiation and disease. However, the analysis of time series single cell RNA-Seq data raises several new computational challenges. Cells at each time point are often sampled from a mixture of cell types, each of which may be a progenitor of one, or several, specific fates making it hard to determine which cells should be used to reconstruct temporal trajectories. In addition, cells, even from the same time point, may be unsynchronized making it hard to rely on the measured time for determining these trajectories. We present TASIC a new method for determining temporal trajectories, branching and cell assignments in single cell time series experiments. Unlike prior approaches TASIC uses on a probabilistic graphical model to integrate expression and time information making it more robust to noise and stochastic variations. Applying TASIC to in vitro myoblast differentiation and in-vivo lung development data we show that it accurately reconstructs developmental trajectories from single cell experiments. The reconstructed models enabled us to identify key genes involved in cell fate determination and to obtain new insights about a specific type of lung cells and its role in development. The TASIC software package is posted in the supporting website. The datasets used in the paper are publicly available. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Coat colours in the Massese sheep breed are associated with mutations in the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes.
Massese is an Italian dairy sheep breed characterized by animals with black skin and horns and black or apparent grey hairs. Owing to the presence of these two coat colour types, this breed can be considered an interesting model to evaluate the effects of coat colour gene polymorphisms on this phenotypic trait. Two main loci have been already shown to affect coat colour in sheep: Agouti and Extension coding for the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes, respectively. The Agouti locus is affected by a large duplication including the ASIP gene that may determine the Agouti white and tan allele (A(Wt)). Other disrupting or partially inactivating mutations have been identified in exon 2 (a deletion of 5 bp, D(5); and a deletion of 9 bp, D(9)) and in exon 4 (g.5172T>A, p.C126S) of the ASIP gene. Three missense mutations in the sheep MC1R gene cause the dominant black E(D) allele (p.M73K and p.D121N) and the putative recessive e allele (p.R67C). Here, we analysed these ASIP and MC1R mutations in 161 Massese sheep collected from four flocks. The presence of one duplicated copy allele including the ASIP gene was associated with grey coat colour (P = 9.4E-30). Almost all animals with a duplicated copy allele (37 out of 41) showed uniform apparent grey hair and almost all animals without a duplicated allele (117 out of 120) were completely black. Different forms of duplicated alleles were identified in Massese sheep including, in almost all cases, copies with exon 2 disrupting or partially inactivating mutations making these alleles different from the A(Wt) allele. A few exceptions were observed in the association between ASIP polymorphisms and coat colour: three grey sheep did not carry any duplicated copy allele and four black animals carried a duplicated copy allele. Of the latter four sheep, two carried the E(D) allele of the MC1R gene that may be the cause of their black coat colour. The coat colour of all other black animals may be determined by non-functional ASIP alleles (non-agouti alleles, A(a)) and in a few cases by the E(D) Extension allele. At least three frequent ASIP haplotypes ([D(5):g.5172T], [N:g.5172A] and [D(5):g.5172A]) were detected (organized into six different diplotypes). In conclusion, the results indicated that coat colours in the Massese sheep breed are mainly derived by combining ASIP and MC1R mutations.


Sentan: a novel specific component of the apical structure of vertebrate motile cilia.
Human respiratory and oviductal cilia have specific apical structures characterized by a narrowed distal portion and a ciliary crown. These structures are conserved among vertebrates that have air respiration systems; however, the molecular components of these structures have not been defined, and their functions are unknown. To identify the molecular component(s) of the cilia apical structure, we screened EST libraries to identify gene(s) that are exclusively expressed in ciliated tissues, are transcriptionally up-regulated during in vitro ciliogenesis, and are not expressed in testis (because sperm flagella have no such apical structures). One of the identified gene products, named sentan, was localized to the distal tip region of motile cilia. Using anti-sentan polyclonal antibodies and electron microscopy, sentan was shown to localize exclusively to the bridging structure between the cell membrane and peripheral singlet microtubules, which specifically exists in the narrowed distal portion of cilia. Exogenously expressed sentan showed affinity for the membrane protrusions, and a protein-lipid binding assay revealed that sentan bound to phosphatidylserine. These findings suggest that sentan is the first molecular component of the ciliary tip to bridge the cell membrane and peripheral singlet microtubules, making the distal portion of the cilia narrow and stiff to allow for better airway clearance or ovum transport.


Services and information for sexually compulsive students on college counseling center websites: results from a national sample.
One factor that may prevent a small but significant percentage of college students from achieving sexual health is sexual compulsivity, a problem of sexual control that is associated with a number of negative health outcomes, including high HIV risk behavior. In this study we content analyzed a randomly selected stratified national sample of 203 4-year U.S. colleges' counseling center websites to assess the degree to which such sites feature information and reference services for sexually compulsive students. Results revealed that sexual compulsivity communications were rare, especially in comparison with communications for other mental health issues. For instance, less than 5% of counseling centers spoke of individual counseling opportunities for students struggling with sexual compulsivity, while between 60% and 80% of counseling centers advertised their capacity to provide individual counseling for students struggling with alcohol and substance abuse, depression, stress/anxiety, and pathological eating. Possible explanations for the paucity of sexual compulsivity messages are discussed.


Single-dose rituximab plus glucocorticoid versus cyclophosphamide plus glucocorticoid in patients with newly diagnosed acquired hemophilia A: A multicenter, open-label, randomized noninferiority trial.
Acquired hemophilia A (AHA) is a rare but serious bleeding disorder. Randomized controlled trial (RCT) comparing the efficacy of immunosuppression therapy for AHA lacks. We conducted the first multicenter RCT aiming to establish whether the single-dose rituximab combination regimen was noninferior to the cyclophosphamide combination regimen. From 2017 to 2022, 63 patients with newly diagnosed AHA from five centers were randomly assigned 1:1 to receive glucocorticoid (methylprednisolone 0.8 mg/kg per day for the first 3 weeks and then tapered) plus single-dose rituximab (375 mg/m2 ; n = 31) or plus cyclophosphamide (2 mg/kg per day until inhibitor becomes negative, for a maximum of 5 weeks; n = 32). The primary outcome was complete remission (CR, defined as FVIII activity ≥50 IU/dL, FVIII inhibitor undetectable, immunosuppression tapered and no bleeding for 24 h without bypassing agents) rate measured within 8 weeks. The noninferiority margin was an absolute difference of 20%. Twenty-four (77.4%) patients in the rituximab group and 22 (68.8%) patients in the cyclophosphamide group achieved CR, which showed the noninferiority of the single-dose rituximab-based regimen (absolute difference = -8.67%, lower limit of the 95% confidence interval = -13.11%; Pnoninferiority = 0.005). No difference was found in the incidence of treatment-related adverse events. Single-dose rituximab plus glucocorticoid regimen showed similar efficacy and safety, without a reported risk of secondary malignancies or reproductive toxicity seen in cyclophosphamide, it might be recommended as a first-line therapy for AHA, especially in China where there is a young age trend in AHA patients. This trial was registered at ClinicalTrials.gov as #NCT03384277.


Synthesis of Realistic Simultaneous Positron Emission Tomography and Magnetic Resonance Imaging Data.
The investigation of the performance of different positron emission tomography (PET) reconstruction and motion compensation methods requires accurate and realistic representation of the anatomy and motion trajectories as observed in real subjects during acquisitions. The generation of well-controlled clinical datasets is difficult due to the many different clinical protocols, scanner specifications, patient sizes, and physiological variations. Alternatively, computational phantoms can be used to generate large data sets for different disease states, providing a ground truth. Several studies use registration of dynamic images to derive voxel deformations to create moving computational phantoms. These phantoms together with simulation software generate raw data. This paper proposes a method for the synthesis of dynamic PET data using a fast analytic method. This is achieved by incorporating realistic models of respiratory motion into a numerical phantom to generate datasets with continuous and variable motion with magnetic resonance imaging (MRI)-derived motion modeling and high resolution MRI images. In this paper, data sets for two different clinical traces are presented, 18F-FDG and 68Ga-PSMA. This approach incorporates realistic models of respiratory motion to generate temporally and spatially correlated MRI and PET data sets, as those expected to be obtained from simultaneous PET-MRI acquisitions.


The use of sentinel node biopsy and selective lymphadenectomy in squamous cell carcinoma of the upper limb. Usefulness of sentinel node biopsy to avoid useless lymphadenectomies in high-risk upper limb SCC.
Squamous cell carcinoma (SCC) is the second most common skin cancer in humans. Because the incidence of metastasis from SCC of the skin is rare, regional lymphadenectomy is generally not recommended for the patients with clinically node-negative disease. However, in patients with an intermediate and high risk of metastasis, evaluation of the lymph nodes to detect the absence of metastatic nodal disease is a difficult task. The authors reviewed the pertinent demographic and surgical data in a consecutive series of six patients with squamous cell carcinoma who underwent sentinel lymph node staging. The tumour size was greater than 2 cm (T2) and the patients had clinically non-palpable regional lymph nodes (N0). All nodes were examined using haematoxylin-eosin staining. Sentinel Lymph Node Biopsy (SLNB) and Selective Lymphadenectomy (SL) using preoperative lymphoscintigraphy and intraoperative radiolymphoscintigraphy and vital dye injections was used to identify the sentinel lymph node avoiding complete axillary node dissection. No false-negative results were observed. At a median follow-up of 10 months (mean 15 months), neither local or regional recurrences in sentinel node-negative basins have been noted. Sentinel node biopsy is a minimally invasive staging procedure useful in identifying occult regional lymph node disease in selected patients with squamous cutaneous malignancies of the arm. Furthermore sentinel lymph node histology is possibly the most important negative predictor of early recurrence and survival in patients with American Joint Committee on Cancer stage I and II squamous cell carcinoma. Although sentinel node-negative patients are a prognostically favourable group, this small series of patients demonstrates that further studies to verify these findings and develop formal guidelines are indicated


Evaluating the Ecological Benefits of Management Actions to Complement Environmental Flows in River Systems.
Globally, many river systems are under stress due to overconsumption of water. Governments have responded with programmes to deliver environmental water to improve environmental outcomes. Although such programmes are essential, they may not be sufficient to achieve all desired environmental outcomes. The benefits of environmental water allocation may be improved using 'complementary measures', which are non-flow-based actions, such as infrastructure works, vegetation management and pest control. The value of complementary measures is recognised globally, but their ecological benefits are rarely well understood, either because there is limited experience with their application, or the importance of context- and location-specific factors make it difficult to generalise benefits. In this study, we developed an approach to evaluate complementary measures at different levels of detail as a mechanism to aid decision-making. For systems that require a rapid, high-level evaluation, we propose a score-based multi-criteria benefit assessment module. If more ecological detail is necessary, we outline a method based on conceptual models, expert elicitation and probability assessment. These results are used to populate a cumulative benefit assessment tool. The tool evaluates the benefits of proposed measures in the wider context by including variables such as flow, dependence on ongoing maintenance and additional ecological values. We illustrate our approach through application to the Murray-Darling Basin, Australia. As many water recovery programmes mature into their evaluation phases, there is an increasing need to evaluate the ecological benefits of including complementary measures in the toolkit available to policy makers.


FOXP1 and KLF2 reciprocally regulate checkpoints of stem-like to effector transition in CAR T cells.
In cancer and infections, self-renewing stem-like CD8+ T cells mediate the response of immunotherapies and replenish terminally exhausted T cells and effector-like T cells. However, the programs governing the lineage choice in chimeric antigen receptor (CAR) T cells are unclear. Here, by simultaneously profiling single-cell chromatin accessibility and transcriptome in the same CAR T cells, we identified heterogeneous chromatin states within CD8+ T cell subsets that foreshadowed transcriptional changes and were primed for regulation by distinct transcription factors. Transcription factors that controlled each CD8+ T cell subset were regulated by high numbers of enhancers and positioned as hubs of gene networks. FOXP1, a hub in the stem-like network, promoted expansion and stemness of CAR T cells and limited excessive effector differentiation. In the effector network, KLF2 enhanced effector CD8+ T cell differentiation and prevented terminal exhaustion. Thus, we identified gene networks and hub transcription factors that controlled the differentiation of stem-like CD8+ CAR T cells into effector or exhausted CD8+ CAR T cells.


Health coaching provided by registered nurses described: a systematic review and narrative synthesis.
The aim of this systematic review and narrative synthesis was to identify how and why health coaching is delivered by Registered Nurses. Systematic review and narrative synthesis. Articles were identified through a search of CINAHL, Medline, Scopus, and PsychINFO databases. Articles published in English between 2010 and 2021 were included. Quality appraisal of relevant literature was independently undertaken by two authors to assess for risk of bias. The Critical Appraisal Skills Program (CASP) was used to appraise quality of potential papers. A main purpose of coaching by Registered Nurses is to optimise patient self-care. How coaching was conducted varied across studies, with the most common coaching approaches via telephone or online. Majority of studies highlight some effectiveness of coaching by nurses; however, some results were inconclusive. Health coaching generally reduced mental distress. Other benefits reported by patients included reduced pain and fatigue. Outcomes for changing lifestyle behaviours were mixed. However, for health coaching to be efficient greater evidence is needed to determine length of time to use coaching, number of habits to focus on to produce change, and to determine best training for coaches. Registered Nurses are most suitable for implementing health coaching for self-care, including preventing and managing chronic illness and recovering from situations like post-surgical needs. Nurses already promote health, and therefore, are skilled in educating people in self-care. Coaching is an additional strategy for motivating, targeting and assessing progress of self-care. Extending the scope of nursing practice to routinely coach in self-care would be ideal.


A stem-loop motif formed by the immediate 5' terminus of the bovine viral diarrhea virus genome modulates translation as well as replication of the viral RNA.
Bovine viral diarrhea virus (BVDV), a Pestivirus member of the Flaviviridae family, has a positive-stranded RNA genome which consists of a single open reading frame (ORF) and untranslated regions (UTRs) at the 5' and 3' ends. The 5' UTR harbors extensive RNA structure motifs; most of them were shown to contribute to an internal ribosomal entry site (IRES), which mediates cap-independent translation of the ORF. The extreme 5'-terminal region of the BVDV genome had so far been believed not to be required for IRES function. By structure probing techniques, we initially verified the existence of a computer-predicted stem-loop motif at the 5' end of the viral genome (hairpin Ia) as well as at the 3' end of the complementary negative-strand replication intermediate [termed hairpin Ia (-)]. While the stem of this structure is mainly constituted of nucleotides that are conserved among pestiviruses, the loop region is predominantly composed of variable residues. Taking a reverse genetics approach to a subgenomic BVDV replicon RNA (DI9c) which could be equally employed in a translation as well as replication assay system based on BHK-21 cells, we obtained the following results. (i) Proper folding of the Ia stem was found to be crucial for efficient translation. Thus, in the context of an authentic replication-competent viral RNA, the 5'-terminal motif operates apparently as an integral functional part of the ribosome entry. (ii) An intact loop structure and a stretch of nucleotide residues that constitute a portion of the stem of the Ia or the Ia (-) motif, respectively, were defined to represent important determinants of the RNA replication pathway. (iii) Formation of the stem structure of the Ia (-) motif was determined to be not critical for RNA replication. In summary, our findings affirmed that the 5'-terminal region of the BVDV genome encodes a bifunctional secondary structure motif which may enable the viral RNA to switch from the translation to the replicative cycle and vice versa.


Comparison of serum phospholipid fatty acids among fishing and farming Japanese populations and American inlanders.
Fatty acid compositions of phospholipids in serum were analyzed in three different populations in seaside fishing and mountain farming villages in Japan and in inland inhabitants of the United States of America. The percentage of omega-3 polyunsaturated fatty acids, i.e., eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) was significantly low in United States inlanders with a high coronary heart disease morbidity compared with both populations in Japan with low morbidity. The level of arachidonic acid (20:4) was the same among these three inhabitant population groups. However, omega-3 polyunsaturated fatty acid levels were significantly higher in the inhabitants of fishing villages with relatively low stroke morbidity than in those of farming villages with extremely high stroke morbidity in Japan.


Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy.
Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved. To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM. Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope. Appropriate ICD intervention terminating ventricular tachycardia or fibrillation. The 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P = .77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%). In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.


Consumption of soymilk lowers atherogenic lipid fraction in healthy individuals.
The effect of soy-based products on lipid profile has not been well established. Whereas some investigators have reported that soy is hypocholesterolemic, others could only demonstrate this in hypercholesterolemic subjects, while a few have not found any marked association between soy and cholesterol levels. This study was therefore aimed at investigating the effect of soymilk on lipid and lipoprotein profile of normocholesterolemic, apparently healthy Nigerian Africans. Five hundred milliliters of soymilk preparation was consumed daily by 42 apparently healthy young to middle-aged subjects for a period of 21 days. Forty-two other volunteers with similar characteristics, who did not drink the soymilk over this time frame, were randomly selected as controls. Plasma total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and triglyceride (TG) concentrations were determined twice by standard spectrophotometric methods (at the initial visit and after 3 weeks). Low-density lipoprotein-cholesterol (LDL-C) was calculated from the TC, TG, and HDL-C concentrations. After 21 days, regulated soymilk consumption significantly reduced mean plasma TC by 11% and LDL-C by 25% (P < .001 and P < .001, respectively) and increased mean plasma HDL-C by 20% (P < .05) in the test population. Plasma TG was not significantly altered. In control subjects, no significant differences were observed in mean TC, LDL-C, HDL-C, and TG. Daily consumption of soymilk significantly decreased atherogenic plasma cholesterol concentration. This suggests that soy drink could be an important non-pharmacological cholesterol-reducing agent.


Alzheimer's disease: recent advances and future perspectives.
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory deficits and other cognitive disturbances. Neuropathologically, AD is characterized by the progressive loss of basal forebrain cholinergic neurons that innervate the hippocampus and cortex and the abnormal extracellular accumulation of amyloid-β and intracellular tau protein. Current research on AD is focused on the mechanisms underlying the abnormal oligomerization, fibrillation, and accumulation of the amyloid-β and tau proteins, mechanisms that may alter the dynamics of this accumulation and on experimental therapeutics approaches aimed at the clearance of the abnormally folded proteins and other potentially neuroprotective interventions. This review will summarize the main areas of investigation in AD and present ways forward for future work.


A construct-first approach to consciousness science.
We propose a new approach to consciousness science that instead of comparing complex theoretical positions deconstructs existing theories, takes their central assumptions while disregarding their auxiliary hypotheses, and focuses its investigations on the main constructs that these central assumptions rely on (like global workspace, recurrent processing, metarepresentation). Studying how these main constructs are anchored in lower-level constructs characterizing underlying neural processing will not just offer an alternative to theory comparisons but will also take us one step closer to empirical resolutions. Moreover, exploring the compatibility and possible combinations of the lower-level constructs will allow for new theoretical syntheses. This construct-first approach will improve our ability to understand the commitments of existing theories and pave the way for moving beyond them.


mTOR and Aging: An Old Fashioned Dress.
Aging is a physiologic/pathologic process characterized by a progressive impairment of cellular functions, supported by the alterations of several molecular pathways, leading to an increased cell susceptibility to injury. This deterioration is the primary risk factor for several major human pathologies. Numerous cellular processes, including genomic instability, telomere erosion, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, stem cell exhaustion, and altered intercellular signal transduction represent common denominators of aging in different organisms. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved nutrient sensing protein kinase that regulates growth and metabolism in all eukaryotic cells. Studies in flies, worms, yeast, and mice support the hypothesis that the mTOR signalling network plays a pivotal role in modulating aging. mTOR is emerging as the most robust mediator of the protective effects of various forms of dietary restriction, which has been shown to extend lifespan and slow the onset of age-related diseases across species. Herein we discuss the role of mTor signalling network in the development of classic age-related diseases, focused on cardiovascular system, immune response, and cancer.


Super-Selective Transarterial Chemoembolization with Doxorubicin-Loaded Drug-Eluting Beads Sized Below and Above 100 Microns in Hepatocellular Carcinoma: A Comparative Study.
Objectives To compare efficacy and safety of super-selective DEB-TACE with doxorubicin-loaded microspheres sized below and above 100 microns for treatment of hepatocellular carcinoma (HCC). Material and methods All consecutive patients with HCC who underwent DEB-TACE were included in this retrospective study. Regarding to microsphere size (>100 microns or <100 microns), patients were determined as Group A (n = 28) and Group B (n = 30), respectively. Results Of the 58 patients (78% males), no statistically significant difference was found between the two groups in terms of age and gender (P = 0.388, P = 0.888, respectively). There were no significant differences between the two groups in terms of BCLC stages, presence of chronic liver disease, and Child-Pugh classes (P = 0.593, P = 0.081, P = 0.391, respectively). Although statistically insignificant, median overall survival (19 months vs 32 months, P = 0.190) and median progression-free survival (13 months vs 20 months (P = 0.574) were longer and 1-3-years objective response rates (7.40% vs 23.33%, P = 0.330) were higher in Group B than in Group A, respectively. No mortality or major complications were observed. Grade I/ II adverse events were detected in all patients. Transient elevations in liver function tests (Grade III adverse events) were similar in both groups (3.57% vs 3.33%; P = 0.980). Conclusion Super-selective DEB-TACE with doxorubicin-loaded microspheres sized <100 microns is an effective and safe method for the HCC treatment. Objective response rates are higher and survival durations are longer after DEB-TACE performed with doxorubicin-loaded microspheres sized below 100 microns. Keywords Chemoembolization Doxorubicin Microspheres Drug-eluting beads Hepatocellular carcinoma.


General cross-coupling reactions with adaptive dynamic homogeneous catalysis.
Cross-coupling reactions are among the most important transformations in modern organic synthesis1-3. Although the range of reported (het)aryl halides and nucleophile coupling partners is very large considering various protocols, the reaction conditions vary considerably between compound classes, necessitating renewed case-by-case optimization of the reaction conditions4. Here we introduce adaptive dynamic homogeneous catalysis (AD-HoC) with nickel under visible-light-driven redox reaction conditions for general C(sp2)-(hetero)atom coupling reactions. The self-adjustive nature of the catalytic system allowed the simple classification of dozens of various classes of nucleophiles in cross-coupling reactions. This is synthetically demonstrated in nine different bond-forming reactions (in this case, C(sp2)-S, Se, N, P, B, O, C(sp3, sp2, sp), Si, Cl) with hundreds of synthetic examples under predictable reaction conditions. The catalytic reaction centre(s) and conditions differ from one another by the added nucleophile, or if required, a commercially available inexpensive amine base.


Preparation and characterization of polyclonal and monoclonal antibodies against human aromatase cytochrome P-450 (P-450AROM), and their use in its purification.
Aromatase cytochrome P-450 (P-450AROM) was partially purified from human placental microsomes by hydrophobic affinity chromatography using Phenyl-Sepharose and ion-exchange chromatography on DEAE-cellulose. The resulting preparation had a specific activity of 2 nmol/mg protein with respect to cytochrome P-450 content and displayed a type I difference spectrum upon addition of the substrate androstenedione. When the cytochrome P-450-enriched fractions were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and stained with Coomassie blue, there was an enrichment of two proteins having apparent molecular weights of 50,000 and 55,000. The bands containing these proteins were removed from unstained polyacrylamide gels and injected separately or together into three rabbits. An aliquot of the serum or an immunoglobulin (IgG) fraction prepared from the serum of the rabbit injected with the 55-kDa band or with both the 50- and 55-kDa bands inhibited aromatase activity of human placental microsomes by 80%; this IgG had no effect on 17 alpha-hydroxylase or 21-hydroxylase activities of human fetal adrenal microsomes. In contrast, the serum of the rabbit injected with the 50-kDa band had little capacity to inhibit placental aromatase activity. By immunoblot analysis, it was found that the IgG from the serum of the rabbit immunized with the 55-kDa protein bound specifically to a protein of 55 kDa in human placental microsomes. Monoclonal antibodies were prepared from a hybridoma cell line derived from the spleen cells of mice immunized against the 55-kDa protein. The monoclonal IgG was covalently linked to a Sepharose 4B column and was used for immunoaffinity chromatography of cytochrome P-450AROM. The finding that cytochrome P-450 and the 55-kDa protein were selectively retained by the affinity column and eluted with NaCl (2 M) and glycine (0.2 M, pH 3.0) and that this fraction contained aromatase activity upon reconstitution with purified NADPH-cytochrome P-450 reductase and phospholipid, is indicative that the 55-kDa protein is indeed cytochrome P-450AROM. These findings are also indicative that both the monoclonal and polyclonal IgGs are specific for human cytochrome P-450AROM.


Multinetwork of international trade: a commodity-specific analysis.
We study the topological properties of the multinetwork of commodity-specific trade relations among world countries over the 1992-2003 period, comparing them with those of the aggregate-trade network, known in the literature as the international-trade network (ITN). We show that link-weight distributions of commodity-specific networks are extremely heterogeneous and (quasi) log normality of aggregate link-weight distribution is generated as a sheer outcome of aggregation. Commodity-specific networks also display average connectivity, clustering, and centrality levels very different from their aggregate counterpart. We also find that ITN complete connectivity is mainly achieved through the presence of many weak links that keep commodity-specific networks together and that the correlation structure existing between topological statistics within each single network is fairly robust and mimics that of the aggregate network. Finally, we employ cross-commodity correlations between link weights to build hierarchies of commodities. Our results suggest that on the top of a relatively time-invariant "intrinsic" taxonomy (based on inherent between-commodity similarities), the roles played by different commodities in the ITN have become more and more dissimilar, possibly as the result of an increased trade specialization. Our approach is general and can be used to characterize any multinetwork emerging as a nontrivial aggregation of several interdependent layers.


A novel molecule "shati" is involved in methamphetamine-induced hyperlocomotion, sensitization, and conditioned place preference.
Drug addiction places an enormous burden on society through its repercussions on crime rate and healthcare. Repeated exposure to drugs of abuse causes cellular adaptations in specific neuronal populations that ultimately can lead to a state of addiction. In the present study, we have identified a novel molecule "shati" from the nucleus accumbens (NAc) of mice treated with methamphetamine (METH) using the PCR-select complementary DNA subtraction method. Moreover, we investigated whether shati is involved in METH-induced hyperlocomotion, sensitization, and conditioned place preference (CPP). METH induced expression of shati mRNA dose dependently via dopamine (DA) receptors. We prepared antibodies against shati and, using them, found shati to be expressed in neuronal cells of the mouse brain. Treatment with the shati antisense oligonucleotide (shati-AS), which significantly inhibited the expression of shati mRNA, enhanced the acute METH response, METH-induced behavioral sensitization, and CPP. Blockage of shati mRNA by shati-AS potentiated the METH-induced increase of DA overflow in the NAc and the METH-induced decrease in synaptosomal and vesicular DA uptake in the midbrain. These results suggest that a novel molecule shati is involved in the development of METH-induced hyperlocomotion, sensitization, and CPP. The functional roles of shati in METH-regulated behavioral alternations are likely to be mediated by its inhibitory effects on the METH-induced increase of DA overflow in the NAc and the METH-induced decrease in DA uptake in the midbrain.


Correlation between Work Engagement and Burnout among Registered Nurses: an Italian hospital survey.
To investigate the correlation between work engagement and burnout among Italian nurses. Work engagement is a protective factor against burnout. Both of them may be affected by the cultural and organizational features of the investigated population, which means that results cannot be generalized. In Italy studies to measure how they correlate have never been performed. Monocentric and quantitative observational study. The Maslach Burnout Inventory and the Utrecht Work Engagement Scale were used on a convenience sample of 318 nurses from an Italian hospital to assess the burnout and work engagement levels and to measure the existing correlation between the two conditions. Work engagement assessment highlighted average values of vigor (57.2%) and absorption (48%), while data referring to burnout demonstrated high levels of emotional exhaustion (55%) and depersonalization (41,5%). The three burnout dimensions and the three work engagement dimensions showed a close and meaningful correlation (p ≤0,01). A correlation between work engagement and burnout has been found. The correlation between Work Engagement and Burnout highlighted in Italian nurses should encourage the implementation of strategies which may enhance work engagement levels to limit burnout, improving the well-being of healthcare workers and significantly influencing the quality of the care process.


Human papilloma virus and survival of oropharyngeal cancer patients treated with surgery and adjuvant radiotherapy.
Impact of p16 protein, a surrogate marker for human papilloma virus induced cancer, p53 and EGFR as well as clinical factors on survival in a patient cohort with oropharyngeal squamous cell carcinoma (OPSCC) treated by surgical resection and adjuvant radiotherapy (RT) ± concomitant chemotherapy (CT). This is a retrospective analysis of patient's charts and tumor tissue. 57 patients were consecutively included and their tumor tissue assembled on a tissue microarray following immunohistochemical analysis. Survival times were estimated by means of Kaplan-Meier analysis. The importance of clinical and immunohistochemical factors for outcome was estimated by cox proportional hazard models. With 88% 5-year overall survival, 91% 5-year disease-specific survival and 91% 5-year disease-free survival, respectively, we found excellent survival rates in this surgically treated patient cohort of mainly advanced OPSCC (93% AJCC stage III or IV). The only factors positively influencing survival were p16 overexpression as well as p53 negativity and even more pronounced the combination of those biomarkers. Survival analysis of patients classified into three risk categories according to an algorithm based on p16, smoking, T- and N-category revealed a low, intermediate and high-risk group with significant survival differences between the low and the high-risk group. Patients with OPSCC can be successfully treated by surgery and adjuvant RT ± CT with a clear survival benefit of p16 positive, p53 negative patients. We recommend considering a combination of immunohistochemical (p16, p53) and clinical factors (smoking, T- and N-category) for risk stratification.


Helicobacter muridarum sp. nov., a microaerophilic helical bacterium with a novel ultrastructure isolated from the intestinal mucosa of rodents.
Helical organisms with novel ultrastructural characteristics were isolated from the intestinal mucosa of rats and mice. These bacteria were characterized by the presence of 9 to 11 periplasmic fibers which appeared as concentric helical ridges on the surface of each cell. The cells were motile with a rapid corkscrewlike motion and had bipolar tufts of 10 to 14 sheathed flagella. The bacteria were microaerophilic, nutritionally fastidious, and physiologically similar to Helicobacter species and Wolinella succinogenes but could be differentiated from these organisms by their unique cellular ultrastructure. Using 16S rRNA sequencing, we found that strain ST1T (T = type strain) was related to previously described Helicobacter species, "Flexispira rappini," and W. succinogenes. The closest relatives of strain ST1T were Helicobacter mustelae and "F. rappini" (average similarity value, 96%). On the basis of phylogenetic data, strain ST1T (= ATCC 49282T) represents a new species of the genus Helicobacter, for which we propose the name Helicobacter muridarum.


Intra-operative events during cardiac surgery are risk factors for the development of delirium in the ICU.
Risk factors for delirium following cardiac surgery are incompletely understood. The aim of this study was to investigate whether intra-operative pathophysiological alterations and therapeutic interventions influence the risk of post-operative delirium. This retrospective cohort study was performed in a 12-bed cardiosurgical intensive care unit (ICU) of a university hospital and included patients consecutively admitted after cardiac surgery during a 2-month period. The diagnosis of delirium was made clinically using validated scores. Comparisons between patients with and without delirium were performed with non-parametric tests. Logistic regression was applied to identify independent risk factors. Results are given as number (percent) or median (range). Of the 194 consecutive post-cardiac surgery patients, 50 (26 %) developed delirium during their ICU stay. Univariate analysis revealed that significant differences between patients with and without delirium occurred in the following intra-operative variables: duration of cardiopulmonary bypass (184 [72-299] vs 113 (37-717) minutes, p < 0.001), lowest mean arterial pressure (50 [30-70] vs 55 [30-75] mmHg, p = 0.004), lowest haemoglobin level (85 [56-133] vs 98 [53-150] g/L, p = 0.005), lowest body temperature (34.5 [24.4-37.2] vs 35.1 [23.9-37.2] °C, p = 0.035), highest noradrenaline support (0.11 [0.00-0.69] vs 0.07 [0.00-0.42] μg/kg/minute, p = 0.001), and frequency of red blood cell transfusions (18 [36 %] vs 26 [18 %], p = 0.018) and platelet transfusions (23 [46 %] vs 24 [17 %], p < 0.001). Only platelet transfusions remained an independent risk factor in the multivariate analysis (p < 0.001). In patients undergoing cardiac surgery, various intra-operative events, such as transfusion of platelets, were risk factors for the development of a post-operative delirium in the ICU. Further research is needed to unravel the underlying mechanisms.


Psychological, social, and behavioral issues for young adults with cancer.
Theories of human development suggest that, although all cancer patients experience a common set of life disruptions, they experience them differently, focus on different issues, and attach different levels of importance to different aspects of the experience depending on the time in life at which they were diagnosed. During the critical developmental transition from childhood to adulthood, older adolescents and young adults in particular have typical concerns with establishing identity, developing a positive body image and sexual identity, separating from parents, increasing involvement with peers and dating, and beginning to make decisions about careers or employment, higher education, and/or family. Accordingly, cancer-related issues such as premature confrontation with mortality, changes in physical appearance, increased dependence on parents, disruptions in social life and school/employment because of treatment, loss of reproductive capacity, and health-related concerns about the future may be particularly distressing for adolescents and young adults. Psychosocial and behavioral interventions for young adult cancer patients and survivors often involve assisting these individuals in retaining or returning to function in significant social roles, such as spouse, parent, student, worker, or friend. Successful interventions will enable these young people to overcome the detrimental impact of a health crisis and strengthen the internal and external coping resources available to them.


[Effectiveness of precautionary chemotherapy in gastric cancer].
Gastric cancer is a very aggressive disease. Surgery is the treatment of choice, with less than 30% 5-year survival for patients with complete resection. Although the incidence of gastric cancer in Western countries has declined progressively in recent decades, the prognosis of the disease has not changed in the last 30 years, with 5-year global survival rates between 7 and 15%. The achievement of an increase in the rate of cure would be therefore an important goal, but the efficacy of adjuvant chemotherapy in this disease is still controversial. The aim of this overview is to document that postoperative chemotherapy may be effective in patients operated with curative intent for gastric cancer. We reviewed the results of randomized trials comparing adjuvant chemotherapy versus surgery alone, divided into those performed in the West and those performed in Asia, and according to publication period. We also reported the preliminary results of an intergroup randomized study of postoperative chemoradiation versus follow-up. Then, we summarized and discussed the results of the 3 meta-analyses, published respectively in 1993, 1999, and 2000, that evaluated the combined results from the over mentioned trials. Singular studies reported conflicting results and failed to show a clear indication for chemotherapy, but they were open to criticisms, due to methodological and therapeutical limitations. The meta-analysis published by Hermans showed a non-significant trend in favor of adjuvant treatment. This analysis was later criticized, and, in response, the author published an update in 1994 in which he recalculated a significant odds ratio. Meta-analyses by Earle and Mari indicated that postoperative chemotherapy produces a small survival benefit in patients with curatively resected gastric carcinoma. Subgroup analyses produced some interesting findings. There was a partial evidence of better results with chemotherapy regimens containing anthracyclines, but it is possible that the results of the ongoing trials testing regimens including cisplatin will add more reliable information about the new regimens. Studies with longer follow-up maintained a trend towards benefit from adjuvant therapy, indicating that long-term survival may be afforded by treatment, as opposed to simply delaying relapse. Finally, there was a trend towards a larger magnitude of the effect when analyses were restricted to trials which included higher risk patients. In conclusion, the results of the 3 meta-analyses suggest that adjuvant chemotherapy may be effective. However, other studies to confirm an effective treatment and to find new therapeutic combination or strategies in the field of adjuvant therapy for gastric carcinoma are warranted.


Comparing effects of tobacco use prevention modalities: need for complex system models.
Many modalities of tobacco use prevention programming have been implemented including various policy regulations (tax increases, warning labels, limits on access, smoke-free policies, and restrictions on marketing), mass media programming, school-based classroom education, family involvement, and involvement of community agents (i.e., medical, social, political). The present manuscript provides a glance at these modalities to compare relative and combined impact of them on youth tobacco use. In a majority of trials, community-wide programming, which includes multiple modalities, has not been found to achieve impacts greater than single modality programming. Possibly, the most effective means of prevention involves a careful selection of program type combinations. Also, it is likely that a mechanism for coordinating maximally across program types (e.g., staging of programming) is needed to encourage a synergistic impact. Studying tobacco use prevention as a complex system is considered as a means to maximize effects from combinations of prevention types. Future studies will need to more systematically consider the role of combined programming.


Clock genes regulate the feeding schedule-dependent diurnal rhythm changes in hexose transporter gene expressions through the binding of BMAL1 to the promoter/enhancer and transcribed regions.
The expression of hexose transporter genes (SGLT1, GLUT5 and GLUT2) in mice with ad libitum feeding under light (7:00-19:00)-dark (19:00-7:00) cycle gradually increased from a basal level at 7:00 and reached a maximum at 19:00, coinciding with the start of dark phase feeding. The peaks of these gene expressions were shifted to 7:00 in mice that were subjected to a restricted feeding schedule from 9:00 to 17:00. The expression of BMAL1, a transcription factor driving the central feedback loop of the clock genes, was followed by the increase of hexose transporter gene expressions. The expressions of Per1-3, genes related to negative regulation of BMAL1, were the highest at or just after the time of maximal expression of the hexose transporter genes in both the group fed ad libitum and the restricted feeding group. Furthermore, chromatin immunoprecipitation assays revealed that the binding of BMAL1 to the promoter and/or transcribed regions of hexose transporters and Per 2 genes was associated with changes in their expressions. These results suggest that diurnal changes in expression of hexose transporter genes depend on the feeding schedule and are directly regulated by a feedback loop of clock genes.


Access to innovation: is there a difference in the use of expensive anticancer drugs between French hospitals?
In DRG-based hospital payment systems, expensive drugs are often funded separately. In France, specific expensive drugs (including a large proportion of anticancer drugs) are fully reimbursed up to national reimbursement tariffs to ensure equity of access. Our objective was to analyse the use of expensive anticancer drugs in public and private hospitals, and between regions. We had access to sales per anticancer drug and per hospital in the year 2008. We used a multilevel model to study the variation in the mean expenditure of expensive anticancer drugs per course of chemotherapy and per hospital. The mean expenditure per course of chemotherapy was €922 [95% CI: 890-954]. At the hospital level, specialisation in chemotherapies for breast cancers was associated with a higher expenditure of anticancer drugs per course for those hospitals with the highest proportion of cancers at this site. There were no differences in the use of expensive drugs between the private and the public hospital sector after controlling for case mix. There were no differences between the mean expenditures per region. The absence of disparities in the use of expensive anticancer drugs between hospitals and regions may indicate that exempting chemotherapies from DRG-based payments and providing additional reimbursement for these drugs has been successful at ensuring equal access to care.


Endoscopic endonasal removal of an intra-suprasellar Rathke's cleft cyst: case report and surgical considerations.
An endoscopic endonasal approach was performed to remove an intra-suprasellar Rathke's cleft cyst. Rathke's cleft cyst are benign lesions, rarely diagnosed because they are often asymptomatic. To the best of our knowledge, at least 475 cases of Rathke's cleft cysts have been reported. They seem to arise from remnants of Rathke's pouch, an invagination of the stomodeum. A 52-year-old woman, complaining of bilateral frontal headaches, was operated on by using an endoscopic endonasal approach, for an intra-suprasellar tumor. The pre-operative diagnosis was non-functioning pituitary adenoma. Intra-operatively a creamy-coloured viscous tissue was found. After the removal of the cyst contents and of the capsule, the suprasellar structures were seen well. The chiasmatic cistern, the chiasm, the pituitary stalk and the pituitary gland were visualized with 0 and 30 degree endoscopes. The pathological findings showed a well-differentiated cuboidal epithelium. The diagnosis was Rathke's cleft cyst. No post-operative complications were observed. The endoscopic technique was particularly suitable in this case, both for the Rathke's cleft features and for an excellent outcome. The Rathke's cleft cyst was easily removed by suction and the cyst wall was entirely removed with curettes and pituitary punches. The hypophysis was distinguished from the cyst and was preserved. The surgical manoeuvres were all done under direct visual control. The absence of nasal packing and of breathing difficulties made comfortable the post-operative outcome. Thus, the endoscopic endonasal approach can be considered the favourite technique in case of either intra- and/or suprasellar Rathke's cleft cysts.


Do Zwicker Tones Evoke a Musical Pitch?
It has been argued that musical pitch, i.e. pitch in its strictest sense, requires phase locking at the level of the auditory nerve. The aim of the present study was to assess whether a musical pitch can be heard in the absence of peripheral phase locking, using Zwicker tones (ZTs). A ZT is a faint, decaying tonal percept that arises after listening to a band-stop (notched) broadband noise. The pitch is within the frequency range of the notch. Several findings indicate that ZTs are unlikely to be produced mechanically at the level of the cochlea and, therefore, there is unlikely to be phase locking to ZTs in the auditory periphery. In stage I of the experiment, musically trained subjects adjusted the frequency, level, and decay time of an exponentially decaying sinusoid so that it sounded similar to the ZT they perceived following a broadband noise, for various notch positions. In stage II, subjects adjusted the frequency of a sinusoid so that its pitch was a specified musical interval below that of either a preceding ZT or a preceding sinusoid (as determined in stage I). Subjects selected appropriate frequency ratios for ZTs, although the standard deviations of the adjustments were larger for the ZTs than for the equally salient sinusoids by a factor of 1.1-2.2. The results suggest that a musical pitch may exist in the absence of peripheral phase locking.


Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Endovascular Thrombectomy.
To determine whether pretreatment cerebral microbleeds (CMBs) presence and burden are correlated with an increased risk of intracranial hemorrhage (ICH) or poor functional outcome following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Consecutive patients treated by EVT for anterior circulation AIS were retrospectively analyzed. Experienced neuroradiologists blinded to functional outcomes rated CMBs on T2*-MRI using a validated scale. We investigated associations of CMB presence and burden with ICH and poor clinical outcome at 3 months (modified Rankin Scale score >2). Among 513 patients, 281 (54.8%) had a poor outcome and 89 (17.3%) had ≥1 CMBs. A total of 190 (37%) patients experienced ICH; 66 (12.9%) were symptomatic. CMB burden was associated with poor outcome in a univariable analysis (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.03-1.36 per 1-CMB increase; p = 0.02), but significance was lost after adjustment for sex, age, stroke severity, hypertension, diabetes mellitus, atrial fibrillation, prior antithrombotic medication, IV thrombolysis, and reperfusion status (OR, 1.05; 95% CI, 0.92-1.20 per 1-CMB increase; p = 0.50). Results remained nonsignificant when taking into account CMB location or presumed underlying pathogenesis. CMB presence, burden, location, or presumed pathogenesis were not independently correlated with ICH. Poor functional outcome or ICH were not correlated with CMB presence or burden on pre-EVT MRI after adjustment for confounding factors. Excluding such patients from reperfusion therapies is unwarranted. This study provides Class II evidence that in patients with AIS undergoing EVT, after adjustment for confounding factors, the presence of CMBs is not significantly associated with clinical outcome or the risk of ICH.


On longitudinal compressive failure of carbon-fibre-reinforced polymer: from unidirectional to woven, and from virgin to recycled.
Modelling the longitudinal compressive failure of carbon-fibre-reinforced composites has been attempted for decades. Despite many developments, no single model has surfaced to provide simultaneously a definitive explanation for the micromechanics of failure as well as validated predictions for a generic stress state. This paper explores the reasons for this, by presenting experimental data (including scanning electron microscopic observations of loaded kink bands during propagation, and brittle shear fracture at 45° to the fibres) and reviewing previously proposed micromechanical analytical and numerical models. The paper focuses mainly on virgin unidirectional (UD) composites, but studies for woven and recycled composites are also presented, highlighting similarities and differences between these cases. It is found that, while kink-band formation (also referred to in the literature as microbuckling) is predominant in UD composites under longitudinal compression, another failure mode related to the failure of the fibres can be observed experimentally. It is also shown that the micromechanics of the failure process observed in UD composites is similar to that in other fibre architectures, hence encouraging the adaptation and application of models developed for the former to the latter.


The effect of ethanolic extract of propolis on radiation-induced mucositis in rats.
To assess the efficacy of ethanolic extract of propolis in radiation-induced mucositis in rats. This study was performed in the Dental Faculty, Shahid Rajaee Hospital of Babol University of Medical Sciences, Babol, Mazandaran, Iran from August 2008 to September 2009, It was carried out on 21 male Wistar rats, age 7-11 weeks, and weighing 16020 g. They were divided into 3 groups. Group A received intraperitoneal (ip) injections of 100 mg/kg ethanolic extract of propolis (EEP), group B received ip injections of 200 mg/kg EEP, and the control group (group C) received 10% ethanol (10 ml/kg [ip]) just before x-ray irradiation. All rats were irradiated in the head and neck region by an x-ray device at a dose rate of 15 gray (Gy) for 9 minutes and 39 seconds. The daily injection continued for the next 10 days, and the lips and tongues of the rats were examined daily to assess the intensity of lesions induced by irradiation. In group C, the first signs of ulcers appeared on the first day, while they appeared on the fourth day in group B, and third day in group A. The severity of ulcers was greatest in group C, and least in group B. Propolis is effective in reducing and delaying radiation-induced mucositis in an animal model, however, further study and evaluation is required.


Hazelnut Allergy: evidence that hazelnut can directly elicit specific IgE antibody response via activating type 2 cytokines in mice.
Hazelnut is one of the major tree nuts that causes potentially fatal food allergy, with underlying mechanisms that are unclear at present. One suggestion is that hazelnut allergy results from immune crossreactivity of IgE antibodies produced against certain aeroallergens. We tested the hypothesis that hazelnut is intrinsically capable of eliciting an allergic response using a mouse model. Groups of mice were injected intraperitoneally with hazelnut/filbert protein extract with or without alum as an adjuvant, and hazelnut-specific antibody (IgE, IgG1) responses were examined using optimized enzyme-linked immunosorbent assay. Hazelnut-specific type 2 and type 1 cytokine responses were evaluated by ex vivo antigen-mediated activation of spleen cells. Hazelnut elicited robust IgE and IgG1 antibody responses. Timecourse and dose-response analyses further provided evidence for memory type 2-dependent antibody responses to hazelnuts. Hazelnut-specific IgE response in two strains of mice with different MHC haplotypes and IgE response to hazelnut without the use of alum adjuvant asserted that hazelnut is intrinsically an allergenic food. The type 2 cytokine analyses revealed that hazelnut sensitization results from activation of IL-4 and IL-5, thus providing a mechanistic basis for hazelnut-specific IgE response. Our data argue that hazelnut - a widely consumed food - is intrinsically an allergenic food capable of directly eliciting hazelnut-binding specific IgE antibodies viaactivation of type 2 cytokines in mice.


AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor.
Pancreatic cancer is one of the leading causes of cancer deaths, with pancreatic ductal adenocarcinoma (PDAC) being the most common subtype. Advanced stage diagnosis of PDAC is common, causing limited treatment opportunities. Gemcitabine is a frequently used chemotherapeutic agent which can be used as a monotherapy or in combination. However, tumors often develop resistance to gemcitabine. Previous studies show that the proto-oncogene PIM kinases (PIM1 and PIM3) are upregulated in PDAC compared to matched normal tissue and are related to chemoresistance and PDAC cell growth. The PIM kinases are also involved in the PI3K/AKT/mTOR pathway to promote cell survival. In this study, we evaluate the effect of the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, and commercially available PIM inhibitor, TP-3654. Using five human PDAC cell lines, we found AUM302 to be a potent inhibitor of cell proliferation, cell viability, cell cycle progression, and phosphoprotein expression, while TP-3654 was less effective. Significantly, AUM302 had a strong impact on the viability of gemcitabine-resistant PDAC cells. Taken together, these results demonstrate that AUM302 exhibits antitumor activity in human PDAC cells and thus has the potential to be an effective drug for PDAC therapy.


Safety climate and injuries: an examination of theoretical and empirical relationships.
Our purpose in this study was to meta-analytically address several theoretical and empirical issues regarding the relationships between safety climate and injuries. First, we distinguished between extant safety climate-->injury and injury-->safety climate relationships for both organizational and psychological safety climates. Second, we examined several potential moderators of these relationships. Meta-analyses revealed that injuries were more predictive of organizational safety climate than safety climate was predictive of injuries. Additionally, the injury-->safety climate relationship was stronger for organizational climate than for psychological climate. Moderator analyses revealed that the degree of content contamination in safety climate measures inflated effects, whereas measurement deficiency attenuated effects. Additionally, moderator analyses showed that as the time period over which injuries were assessed lengthened, the safety climate-->injury relationship was attenuated. Supplemental meta-analyses of specific safety climate dimensions also revealed that perceived management commitment to safety is the most robust predictor of occupational injuries. Contrary to expectations, the operationalization of injuries did not meaningfully moderate safety climate-injury relationships. Implications and recommendations for future research and practice are discussed.


Multicenter evaluation of a topical antioxidant serum.
A new antioxidant serum has been formulated with sodium ascorbate, a sodium salt of Vit C, which aims to address facial photodamage while maintaining a low irritation profile and preserving elastin. Detailed background science has been submitted in a previous publication. This open-label study was conducted to validate the science by demonstrating product efficacy and tolerability in patients with moderate to severe facial photodamage. A multicenter, open-label clinical study was undertaken over 5 months from March 2023 to July 2023. Thirty six eligible participants (35 female, 1 male), aged 38-69 years, and Fitzpatrick skin types II-V were enrolled into and completed the study following 12 weeks of the topical antioxidant serum use twice daily, along with the following supporting products (gentle cleanser, moisturizer, and sunscreen for as needed use). Follow-up visits were conducted in Weeks 2, 4, 8, and 12. At every visit, participants were evaluated for facial photodamage severity and test product tolerability. Additionally, study participants underwent subject assessments and satisfaction questionnaires, investigator assessments, biopsy collection, and photography. Significant improvements in all evaluated facial photodamage parameters were observed at 12 weeks together with excellent tolerability and subject satisfaction persisting to Week 12 at study completion. Histology most notably revealed increased elastin fibers in 5 out of 5 post 12-week treatment biopsies on Movat staining, while Herovici stains revealed stimulation of collagen and early formation of new fibers. A novel antioxidant serum has demonstrated to be safe and effective for addressing facial photodamage, while stimulating the production of both elastin and collagen in the extracellular matrix (ECM).


Cellular Auxetic Structures for Mechanical Metamaterials: A Review.
Recent advances in lithography technology and the spread of 3D printers allow us a facile fabrication of special materials with complicated microstructures. The materials are called "designed materials" or "architectured materials" and provide new opportunities for material development. These materials, which owing to their rationally designed architectures exhibit unusual properties at the micro- and nano-scales, are being widely exploited in the development of modern materials with customized and improved performance. Meta-materials are found to possess superior and unusual properties as regards static modulus (axial stress divided by axial strain), density, energy absorption, smart functionality, and negative Poisson's ratio (NPR). However, in spite of recent developments, it has only been feasible to fabricate a few such meta-materials and to implement them in practical applications. Against such a backdrop, a broad review of the wide range of cellular auxetic structures for mechanical metamaterials available at our disposal and their potential application areas is important. Classified according to their geometrical configuration, this paper provides a review of cellular auxetic structures. The structures are presented with a view to tap into their potential abilities and leverage multidimensional fabrication advances to facilitate their application in industry. In this review, there is a special emphasis on state-of-the-art applications of these structures in important domains such as sensors and actuators, the medical industry, and defense while touching upon ways to accelerate the material development process.


Molecular and biochemical characterization of dehydroascorbate reductase from a stress adapted C4 plant, pearl millet [Pennisetum glaucum (L.) R. Br].
PgDHAR was isolated from Pennisetum glaucum. PgDHAR responded to abiotic stress and exhibited enzyme activity at broad ranges of temperature, pH and substrate concentrations suggesting its role in stress tolerance. Dehydroascorbate reductase (EC 22.214.171.124) is a crucial enzyme actively involved in the recycling of ascorbate redox pool in the cellular environment. In this study, the full-length cDNA coding for DHAR polypeptide and its corresponding gene was isolated from Pennisetum glaucum (PgDHAR). PgDHAR encodes a polypeptide of 213 amino acids with a predicted molecular mass of 23.4 kDa and shares 80-75 % sequence homology with DHAR from other plants. The heterologously expressed recombinant PgDHAR protein exhibited activity in a wide range of substrate concentrations. The recombinant PgDHAR is thermostable and retains its activity over a broad pH range. Furthermore, transcript level of PgDHAR is quantitatively up-regulated in response to temperature. On the whole, PgDHAR alone or in combination with other genes of ascorbate-glutathione cycle can be used for the development of stress tolerant as well as nutritionally improved food crop with enhanced ascorbic acid content.


Acute progesterone and 17 beta-estradiol modulation of luteinizing hormone secretion by pituitaries of cycling rats superfused in vitro.
During the rat estrous cycle there are marked changes in the concentrations of serum 17 beta-estradiol (E2) and progesterone. The objective of the present study was to examine the acute effects of E2 and progesterone on isolated pituitaries obtained at 1230 h at each stage of the 4-day cycle. At time zero, single quartered anterior pituitaries were placed in a chamber and superfused at 0.5 ml/min with medium 199 with or without steroids for 360 min; sequential 10-min effluent samples were collected. LHRH (10 ng/ml) was administered as two successive 10-min pulses at 120 and 240 min. The proestrous and the diestrous-II pituitaries in vitro exhibited the characteristic LHRH self-priming response: an increased LH secretory response to a second pulse of LHRH in both the absence and presence of steroids in the superfusion medium; however, the magnitude of the response to the initial pulse of LHRH was reduced significantly when E2 (50 pg/ml) was present. The presence of progesterone (50 ng/ml) resulted in a marked augmentation of the LH secretory response to the first pulse of LHRH; when both E2 and progesterone were included in the superfusion medium, the stimulatory effect of progesterone was reduced. The progesterone augmentation of LHRH-induced LH secretion was present after 60 min of steroid exposure in vitro but was not demonstrable after only 10 min of exposure. Cycloheximide inhibited the progesterone augmentation and the LHRH self-priming without affecting the LH secretory response to the initial LHRH pulse in the absence of steroid. Progesterone augmentation was not observed on estrus and diestrous-I. The presence of E2 in the medium, however, resulted in a significant decrease in the response to the first pulse of LHRH for pituitaries from either estrus or diestrous-I. These data 1) demonstrate that E2 by itself suppresses LHRH-induced LH secretion by the proestrous pituitary and 2) provide proof for a direct stimulatory action of progesterone, in the absence of E2, on the proestrous pituitary and suggest a positive feedback role for progesterone during the preovulatory LH surge. (Endocrinology 108: 413, 1981)


The assessment of the serum C-peptide and plasma glucose levels by orally administered whey proteins in type 2 diabetes mellitus.
A personalized antidiabetic therapy is not yet part of the official guidelines of professional societies for clinical practice. The aim of this study was to evaluate the serum C-peptide and plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) after oral administration of whey proteins. Sixteen overweight T2DM Caucasians with good glycemic control and with preserved fasting serum C-peptide levels (>200 nmol/l) were enrolled in this study. Two oral stimulation tests - one with 75 g of glucose (OGTT) and the other with 75 g of whey proteins (OWIST) - were administered for assessing serum C-peptide and plasma glucose levels in each participant. Both oral tests induced similar pattern of C-peptide secretion, with a peak at 90 min. The serum C-peptide peak concentration was 2.91+/-0.27 nmol/l in OWIST, which was 22 % lower than in OGTT. Similarly, the C-peptide iAUC(0-180) were 32 % lower in the OWIST than in the OGTT (p<0.01). Contrary to OGTT the OWIST did not cause a significant increase of glycemia (p<0.01). Our study showed that the OWIST represents a useful tool in estimation of stimulated serum C-peptide levels in patients with T2DM.


A community partnership to respond to an outbreak: a model that can be replicated for future events.
Nassau County Department of Health (NCDOH) found itself in the midst of the initial U.S. outbreak of the H1N1 influenza global pandemic. A coordinated, collaborative approach to address the outbreak was needed. Yet, a description of a multisector community partnership during an influenza pandemic has not been described in the literature. This article reports the efforts taken by a local health department to partner with the community utilizing a three-phase model to communicate, plan, and implement a strategy to ease the fear that existed and to minimize the illness in the region. This article describes in detail critical components of the community wide partnership. Lessons learned from this event are highlighted which have implications for future public health policy. The key points to the article are that there are three critical phases to successful community partnership during an influenza outbreak: Communication, planning, and implementation. The learning points include that communication is paramount, creation of partnerships is vital to a successful implementation phase, and public health funds are leveraged more effectively by collaborating with community partners. The NCDOH's multisector partnership with hospitals, physicians, and community organizations to address the H1N1influenza pandemic was nontraditional and allowed for leveraging of public health resources. The three-phase model can be replicated for future infectious disease outbreaks.