Parallel two-step phase-shifting point-diffraction interferometry for microscopy based on a pair of cube beamsplitters.
Parallel two-step phase-shifting point-diffraction interferometry for microscopy based on a pair of cube beamsplitters is proposed. The first 45°-tilted cube beamsplitter splits object wave into two parallel copies: one copy is filtered by a pinhole in its Fourier plane to behave as reference wave, while the other one remains unchanged as object wave. The second cube beamsplitter combines the object and reference waves, and then split them together into two beams. Along with the two beams, two parallel phase-shifting interferograms are obtained in aid of polarization elements. Based on the proposed configuration, slightly-off-axis interferometry for microscopy is performed, which suppresses dc term by subtracting the two phase-shifting holograms from each other. The setup is highly stable due to its common-path configuration, and has been demonstrated to be suitable for measuring moving objects or dynamic processes.


Decreased cortisol secretion by adrenal glands perfused with the P-glycoprotein inhibitor valspodar and mitotane or doxorubicin.
The aim of this study was to investigate the role of P-glycoprotein (P-gp) in the adrenal gland. It has been presumed that P-gp, rather than being involved in physiological cortisol secretion, plays a role in protecting the adrenacortical cells from xenobiotics. To explore this a study was performed on perfused bovine adrenal glands. Individual experimental groups were perfused with either a selective P-gp blocker (valspodar) alone, with a xenobiotic (mitotane or doxorubicin) alone or with both valspodar and a xenobiotic. The cumulative amounts of cortisol secreted in each individual group were calculated and the two-sample t-test was used to compare the mean values of cumulative amounts. The mean value of cortisol secreted from the group of adrenals perfused with the P-gp blocker was not significantly different from that of the control group. Treatment with either mitotane or doxorubicin decreased the amount of cortisol secreted but not significantly when compared to the amount of cortisol secreted in basal conditions. However, treatment with the P-gp blocker valspodar in addition to either mitotane or doxorubicin significantly decreased cortisol secreted compared to the amount of cortisol secreted by the glands treated with either mitotane (p=0.009) or doxorubicin (p=0.017) alone. The regressive changes discovered in all experimental groups were most prominent when valspodar was used with either mitotane or doxorubicin. We found that P-gp blockade increases by xenobiotic (mitotane and doxorubicin)-induced damage of adrenocortical cells, which points to a role of P-gp in the protection of adrenal gland from xenobiotics.


Protective Effects of Sodium Para-aminosalicylic Acid on Manganese-Induced Damage in Rat Pancreas.
Sodium p-aminosalicylic acid (PAS-Na) has been previously shown to protect the brain from manganese (Mn)-induced toxicity. However, the efficacy of PAS-Na in protecting other organs from Mn toxicity and the mechanisms associated with this protection have yet to be addressed. Therefore, here, we assessed pancreatic damage in response to Mn treatment and the efficacy of PAS-Na in limiting this effect, along with specific mechanisms that mediate PAS-Na's protection. Mn exposure led to increased blood Mn content in dose- and time-dependent manner. Furthermore, subchronic Mn exposure (20 mg/kg for 8 weeks) led to pancreatic damage in a dose-dependent manner. In addition, the elevated Mn levels increased iron and decreased zinc and magnesium content in the pancreas. These effects were noted even 8 weeks after Mn exposure cessation. Mn exposure also affected the levels of amylase, lipase, and inflammatory factors such as tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1β). PAS-Na significantly inhibited the increase in Mn concentration in both blood and pancreas, restored Mn-induced pancreatic damage, reversed the Mn-induced alterations in metal levels, and restored amylase and lipase concentrations. Taken together, we conclude that in rats, PAS-Na shows pharmacological efficacy in protecting the pancreas from Mn-induced damage.


Millimetric sky opacity measurements from the South Pole.
The opacity of the sky above the South Pole was measured in the millimetric atmospheric windows. We found the opacity to range from 0.1 to 0.2 implying very low water vapor column density. The low water vapor content makes the South Pole ideal for astrophysical observations in the infrared and millimetric windows.


Urinary mutagenicity and colorectal adenoma risk.
We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenicity was determined in Salmonella YG1024 +S9 (Ames test). Adenoma risk was 2.4-fold higher in subjects in the highest versus the lowest quintile of urinary mutagenicity (95% confidence interval = 1.1-5.1). Combining urinary mutagenicity with intake of meat-derived mutagenicity (from our earlier analysis) resulted in a 5.6-fold increase in adenoma risk (95% confidence interval = 2.2-13.9, comparing the highest with the lowest quintile). In our study population, diet may have contributed to mutagenic exposure, which was positively associated with colorectal adenoma risk.


RbAp48 regulates cytoskeletal organization and morphology by increasing K-Ras activity and signaling through mitogen-activated protein kinase.
RbAp48 is a WD-40 protein that plays an important role in chromatin metabolism and regulates Ras signaling. Here, we report that RbAp48 is involved in the regulation of cytoskeletal organization, a novel function. First, we show that transfection of RbAp48 into Hs-578T breast cancer cells (Hs-RbAp48-hi) leads to cell size reduction, a rounded cell shape, decreased cellular protrusions, and a higher nuclear/cytoplasmic ratio. Furthermore, we observed cytoskeletal F-actin organization disruption with loss of actin stress fibers and formation of membranous F-actin rings in Hs-RbAp48-hi cells. These morphologic changes were partially reversed by RbAp48 knockdown. Interestingly, mitogen-activated protein kinase (MAPK) was activated in Hs-RbAp48-hi cells, and this activity was also partly reversed by RbAp48 down-regulation. Furthermore, pharmacologic inhibition of MAPK led to the reappearance of organized actin fibers and focal contacts, suggesting MAPK as the effector pathway. Moreover, we show an increase in total Ras activity in Hs-RbAp48-hi cells with K-Ras-GTP becoming the dominant isoform. This reverted to baseline activity levels on RbAp48 small interfering RNA transfection, thus suggesting a direct role for RbAp48 in Ras regulation. Finally, we tested the model in transformed 3T3-K-Ras-G12V fibroblasts. As expected, RbAp48 knockdown in 3T3-K-Ras-hi fibroblasts resulted in reappearance of an organized cytoskeleton and shutdown of K-Ras activity. In conclusion, our data support a model whereby RbAp48 regulates cellular morphology and cytoskeletal organization by increasing K-Ras activity and signaling through MAPK.


Accurate K-edge X-ray photoelectron and absorption spectra of g-C3N4 nanosheets by first-principles simulations and reinterpretations.
We performed a density functional theory (DFT) study on X-ray photoelectron (XPS) and absorption (XAS) spectra of graphitic carbon nitride (g-C3N4) nanosheets at the N and C K-edges. A combined cluster-periodic approach was employed to calculate XPS spectra, in which the core ionic potential (IP) of the solid 2D material was computed by subtracting the work function (obtained with periodic conditions) from the gas phase IP (obtained with large cluster models). With amino-terminated supermolecules of different sizes, we obtained convergent spectra and provide new assignments for 5 nitrogen [1 sp2; 4 sp3 (bridging, tertiary, and primary/secondary amino nitrogens)] and 4 carbon (all bonded with three nitrogens) local structures. A good agreement with experiments was obtained, with the N1s (C1s) main peak position differing by 0.1-0.2 eV (0.5-0.8 eV). Our simulations show that N1s XPS of pure g-C3N4 contains only two major features at 398.6 and 401.2 eV, contributed from sp2-N and sp3-N, respectively. The chemical shifts of all sp3-N are so close (deviating by 0.3-0.6 eV) that terminal amino groups -NHx (x = 1, 2) will only be distinguished in high-resolution measurements. In C1s XPS, all carbons show similar (deviation < 0.2 eV) IPs, as determined by the same nearest neighbors. We further excluded the effect of shake-up satellites that may change our XPS interpretations by equivalent core hole time-dependent DFT (ECH-TDDFT) simulations. The effect of vibronic coupling is small (redistribution is only 0.1-0.3 eV to the higher-energy region) in the N1s edge as estimated from the asymmetric main peak shape, and negligible in the C1s edge. Quicker size convergence was found in XAS than XPS. In N1s XAS, we identified a weak π* spectral feature at 400-401 eV for both -NHx and tertiary nitrogens. Our study provides a clear theoretical reference for X-ray spectral fingerprints of different local structures, which is useful for analysis of g-C3N4 based materials with various designed or unavoidable structural modifications. We also highlight our combined cluster-periodic approach in calculating the K-edge XPS spectra of general 2D materials which predicts accurate absolute values.


Preparation and chromatographic properties of a multimodal chiral stationary phase based on phenyl-carbamate-propyl-beta-CD for HPLC.
A phenylcarbamate derivative of 2-hydroxypropyl-beta-CD bonded stationary phase was prepared by a previously described method. Its enantiomeric recognition abilities were evaluated as chiral stationary phase (CSP) in normal, polar organic and RP conditions by HPLC. The relevant structural features of the prepared stationary phase which make it an effective chiral selector are discussed. This material seems to have an excellent enantioselectivity for a variety of racemic analytes in the three modes. Hence it can be considered a highly effective multimodal column. Retention factor (k), selectivity (alpha) and resolution (R(s)) were the chosen parameters to describe the column performance. Optimization of these separations was discussed in terms of mobile phase composition, flow rate and structural patterns of the injected analytes.


Society of Pediatric Psychology Workforce Survey: Factors Related to Compensation of Pediatric Psychologists.
To summarize compensation results from the 2015 Society of Pediatric Psychology (SPP) Workforce Survey and identify factors related to compensation of pediatric psychologists. All full members of SPP ( n = 1,314) received the online Workforce Survey; 404 (32%) were returned with usable data. The survey assessed salary, benefits, and other income sources. The relationship between demographic and employment-related factors and overall compensation was explored. Academic rank, level of administrative responsibility, and cost of living index of employment location were associated with compensation. Compensation did not vary by gender; however, women were disproportionately represented at the assistant and associate professor level. Compensation of pediatric psychologists is related to multiple factors. Longitudinal administration of the Workforce Survey is needed to determine changes in compensation and career advancement for this profession over time. Strategies to increase the response rate of future Workforce Surveys are discussed.


Nanoscale metal-organic frameworks coated with poly(vinyl alcohol) for ratiometric peroxynitrite sensing through FRET.
This work describes a facile yet powerful approach to energy-transfer NMOF (nanoscale metal-organic framework) fabrication for ratiometric peroxynitrite (ONOO-) sensing. Poly(vinyl alcohol) (PVA) is chosen to organize the energy donor (NMOF) and acceptor (molecular probes). PVA can conveniently graft onto the NMOF surface and bind to the molecular probes bearing the arylboronic acid group through multiple weak coordination interactions. Due to efficient Förster resonance energy transfer (FRET), the bright blue fluorescence of the NMOF is quenched while the green or red emission from the acceptor is enhanced. Upon reacting with ONOO-, the ONOO- sensors depart from the NMOF and the FRET is interrupted and the fluorescence of the NMOF recovered. Based on this strategy, we developed two ratiometric ONOO- nanosensors for the detection of ONOO- in solutions and living cells. This work is the first report of NMOF ONOO- sensors through FRET and could inspire the design of other NMOF based chemical sensors and biosensors.


Senses of responsibility. A challenge for occupational and physical therapists in the context of ongoing professionalization.
The aim of this paper was to delineate different senses of responsibility in the therapeutic relationship between occupational and physical therapists and their patients, in the context of ongoing professionalization. To assist the analysis of the therapists' responsibilities, Ozar's guild and interactive relationship models were employed. The questions with regard to each model asked how the model might be used in order to describe the therapists' professional development in general, and specifically their professional responsibilities. Based on earlier findings, the professional development of the therapy groups has developed in line with both the guild and interactive models, i.e. some therapists have adopted the former and others the latter. Whether therapists in general, in recent years, have shifted their paradigm, and consequently also their choice of relationship model, is a question that necessitates further research. However, based on the results from the analysis here, it seems relevant to propose that therapists, with a renewed sense of urgency, should use Ozar's models as tools for reflection on the development of their professional responsibilities in the therapist-patient relationship, in the frame of a rehabilitation paradigm.


Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.
Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. To evaluate the safety and efficacy of tezacaftor monotherapy and of tezacaftor/ivacaftor combination therapy in subjects with cystic fibrosis homozygous for F508del or compound heterozygous for F508del and G551D. This was a randomized, placebo-controlled, double-blind, multicenter, phase 2 study (NCT01531673). Subjects homozygous for F508del received tezacaftor (10 to 150 mg) every day alone or in combination with ivacaftor (150 mg every 12 h) in a dose escalation phase, as well as in a dosage regimen testing phase. Subjects compound heterozygous for F508del and G551D, taking physician-prescribed ivacaftor, received tezacaftor (100 mg every day). Primary endpoints were safety through Day 56 and change in sweat chloride from baseline through Day 28. Secondary endpoints included change in percent predicted FEV1 (ppFEV1) from baseline through Day 28 and pharmacokinetics. The incidence of adverse events was similar across treatment arms. Tezacaftor (100 mg every day)/ivacaftor (150 mg every 12 h) resulted in a 6.04 mmol/L decrease in sweat chloride and 3.75 percentage point increase in ppFEV1 in subjects homozygous for F508del, and a 7.02 mmol/L decrease in sweat chloride and 4.60 percentage point increase in ppFEV1 in subjects compound heterozygous for F508del and G551D from baseline through Day 28 (P < 0.05 for all). These results support continued clinical development of tezacaftor (100 mg every day) in combination with ivacaftor (150 mg every 12 h) in subjects with cystic fibrosis. Clinical trial registered with www.clinicaltrials.gov (NCT01531673).


Chinese Hospitalized Cardiovascular Patients' Attitudes Towards Self-Management: A Qualitative Study.
This study is aiming to investigate cardiovascular patients' attitudes towards self-management during hospitalization in China. Twenty-nine individuals living with cardiovascular disease from one designated Cardiology Department in Hangzhou, China, were recruited through a purposive sampling procedure. A qualitative descriptive methodology was used. Semi-structured interviews were also used to gain attitudes toward self-management. The interviews were audio-recorded, transcribed and analyzed by thematic analysis to develop the results. Four themes were identified from the qualitative data: (1): Responsibilities of self-management; (2): Reflections on self-management; (3): Acknowledgement of self-management support; (4): Challenges in implementing and adherence to self-management. Additionally, interview data were also given to illustrate these main themes emerging during the analysis. Patients gradually took their responsibilities to manage chronic symptoms. During their self-management process, they did reflections to help correct their regiments through supportive interactions. Health system responsiveness, health disparities, social capital, and cultural setting were the main external factors influencing better self-management implementation and adherence. This study revealed the hospitalized cardiovascular patients' attitudes towards self-management in China. These findings emphasized the importance of patients' responsibility, reflections, and various social support receiving and pointed out specific external factors influencing the health outcomes and their quality of life. This study also proves the guide for the policymakers and health system better instructions to develop individually and culturally tailored advanced self-management interventions and programs.


Metastatic trophoblastic disease presenting as a subarachnoid hemorrhage: report of two cases and review of the literature.
Trophoblastic tumors may present as subarachnoid or intracerebral hemorrhages in women of childbearing age. Although uncommon in Western countries, they constitute a significant percentage of metastatic lesions to the nervous system among Oriental women and usually follow molar pregnancies. Malignant transformation may occur at any time, but most frequently within a year of pregnancy. For this reason, close follow-up of women with molar pregnancies and subsequent prevention of pregnancy for one year is mandatory. Persistent serum human chorionic gonadotropin elevations are seen at some stage. Eighty percent of hydatidiform moles remit spontaneously, and the prognosis for persistent molar disease treated with chemotherapy and irradiation is good. The prognosis for choriocarcinoma, however, is less favorable. Subarachnoid hemorrhage may be the first and only sign of intracerebral bleeding into a metastatic lesion or leakage from a damaged vessel in which trophoblastic tissue has lodged. The triad of menstrual abnormalities, recent or remote pregnancy or abortion, and an acute cerebrovascular event with evidence of a mass lesion should suggest the diagnosis of metastatic trophoblastic disease in a woman of childbearing age.


Case management can reduce costs and protect revenues.
In order to reduce costs, improve quality, and protect revenues, an integrated healthcare system should depend heavily on a case management program that provides continuity of care across all clinical settings for an entire episode of illness or injury. In addition, such a program should move homogeneous, uncomplicated groups of patients quickly and cost effectively through the healthcare delivery system and determine why other patients are not able to move through the system as quickly and effectively.


Substrate specificity of Schizosaccharomyces pombe Nth protein for products of oxidative DNA damage.
A gene from Schizosaccharomyces pombe, which encodes a protein with a strong sequence similarity to the Nth protein of Escherichia coli, has recently been identified [Roldán-Arjona, T., Anselmino, C., and Lindahl, T. (1996) Nucleic Acids Res. 24, 3307-3312]. The functional analysis of this eukaryotic enzyme indicated that it is a homologue of E. coli Nth protein. The gene has been subcloned and the protein (Nth-Spo) purified to apparent homogeneity. We investigated the substrate specificity of this eukaryotic enzyme for modified bases in oxidatively damaged DNA, using the technique of gas chromatography/isotope-dilution mass spectrometry (GC/IDMS). DNA substrates containing up to 17 types of modified bases were prepared by gamma-irradiation or by treatment with H2O2 in the presence of Fe(III)-EDTA or Cu(II). The results revealed an efficient excision of five pyrimidine-derived lesions, 5-hydroxycytosine, thymine glycol, 5-hydroxy-6-hydrothymine, 5,6-dihydroxycytosine, and 5-hydroxyuracil. None of the other pyrimidine or purine lesions was excised. Excision was measured as a function of enzyme concentration, time, substrate concentration, and temperature. Kinetic constants were determined. Although some DNA base lesions removed by Nth-Spo protein were similar to those previously described for E. coli Nth protein, differences between substrate specificities of these two enzymes were noted.


Valorizing the Unexplored Filtration Waste of Brewing Industry for Green Silver Nanocomposite Synthesis.
The brewing industry generates a substantial amount of by-products rich in polyphenols, carbohydrates, sugars, sulfates, nitrogen compounds, organic carbon, and several elements, including chlorine, magnesium, and phosphorus. Although limited quantities of these by-products are used in fertilizers and composts, a large amount is discarded as waste. Therefore, it is crucial to identify different ways of valorizing the by-products. Research regarding the valorization of the brewery by-products is still in its nascent stage; therefore, it still has high potential. Herein, we report the valorization of the brewery by-product from the filtration stage of the brewing process (BW9) to synthesize silver nanocomposites as this waste has remained largely unexplored. The BW9 nanocomposites have been compared to those obtained from the brewery product B. The chemical composition analysis of BW9 and B revealed several organic moieties capable of reducing metal salts and capping the formed nanoparticles. Therefore, the brewery waste from stage 9 was valorized as a precursor and added to silver-based precursor at various temperatures (25, 50, and 80 °C) and for various time periods (10, 30, and 120 min) to synthesize silver nanocomposites. The nanocomposites obtained using BW9 were compared to those obtained using the main product of the brewing industry, beer (B). Synthesized nanocomposites composed of AgCl as a major phase and silver metal (Agmet) was incorporated in minor quantities. In addition, Ag3PO4 was also found in B nanocomposites in minor quantities (up to 34 wt.%). The surface morphology depicted globular nanoparticles with layered structures. Small ball-like aggregates on the layer representative of Ag3PO4 were observed in B nanocomposites. The surface of nanocomposites was capped with organic content and functional groups present in the brewery products. The nanocomposites demonstrated high antibacterial activity against Escherichia coli (E. coli), with BW9 nanocomposites exhibiting a higher activity than B nanocomposites.


Antibacterial and antioxidant activities of endophytic fungi and nettle (Urtica dioica L.) leaves as their host.
Nettle (Urtica dioica L), as a plant rich in biologically active compounds, is one of the most important plants used in herbal medicine. Studies have shown that this plant has antioxidant, antiplatelet, hypoglycemic and hypocholesterolemia effects. In this study, we characterized three Alternaria endophytic fungi isolated from their host U. dioica. We hypothesized that these endophytic fungi can produce new bioactive metabolites, which may possess the bioactive property with potential application in the medical and pharmaceutical industries. The antibacterial activity was evaluated against reference and isolated strains, including Methicillin-Resistant Staphylococcus aureus. A wide range of antimicrobial activities similar to those measured in nettle leaves was detected especially for Alternaria sorghi. Furthermore, the highest antioxidant activity detected with DPPH free radical scavenging was measured for A. sorghi and nettle leaves ethyl acetate extracts. In addition, whereas catalase activity was similar in the three isolated fungi and nettle leaves, total thiol content and superoxide dismutase activity were significantly higher in leaves. A. sorghi showed the best activities compared to other isolated fungi. The characterization and further production of bioactive compounds produced by this endophyte should be investigated to fight bacteria and especially those that develop drug multi-resistance.


Crystallization and preliminary crystallographic analysis of the extracellular fragment of FcalphaRI/CD89.
Crystals of the extracellular fragment of FcalphaRI/CD89 have been grown at 291 K using PEG 8000 as precipitant. The diffraction pattern of the selenomethionine (SeMet) derivative crystal extended to 2.1 A resolution at SPring-8, Japan. The crystals belong to space group C222(1), with unit-cell parameters a = 59.0, b = 69.4, c = 106.3 A, alpha = beta = gamma = 90 degrees. The presence of one molecule per asymmetric unit gives a crystal volume per protein mass (V(M)) of 3.12 A(3) Da(-1) and a solvent content of 60.2% by volume. A full set of X-ray diffraction data were collected to 2.1 A from an SeMet-derivative crystal.


Identification of the genetic basis for clinical menadione-auxotrophic small-colony variant isolates of Staphylococcus aureus.
Small-colony variants (SCVs) of Staphylococcus aureus are associated with persistent infections and may be selectively enriched during antibiotic therapy. Three pairs of clonally related S. aureus isolates were recovered from patients receiving systemic antibiotic therapy. Each pair consisted of an isolate with a normal phenotype and an isolate with an SCV phenotype. These SCVs were characterized by reduced susceptibility to gentamicin, reduced hemolytic activity, slow growth, and menadione auxotrophy. Sequencing of the genes involved in menadione biosynthesis revealed mutations in menB, the gene encoding naphthoate synthase, in all three strains with the SCV phenotype. The menB mutations were (i) a 9-bp deletion from nucleotides 55 to 63, (ii) a frameshift mutation that resulted in a premature stop codon at position 230, and (iii) a point mutation that caused the amino acid substitution Gly to Val at codon 233. Fluctuation tests showed that growth-compensated mutants arose in the SCV population of one strain, strain OM1b, at a rate of 1.8 x 10(-8) per cell per generation. Sequence analyses of 23 independently isolated growth-compensated mutants of this strain revealed alterations in the menB sequence in every case. These alterations included reversions to the wild-type sequence and intragenic second-site mutations. Each of the growth-compensated mutants showed a restoration of normal growth and a loss of menadione auxotrophy, increased susceptibility to gentamicin, and restored hemolytic activity. These data show that mutations in menB cause the SCV phenotype in these clinical isolates. This is the first report on the genetic basis of menadione-auxotrophic SCVs determined in clinical S. aureus isolates.


Effect of dietary phytase transgenic corn on physiological characteristics and the fate of recombinant plant DNA in laying hens.
The study aimed to evaluate the potential effects of feeding with phytase transgenic corn (PTC) on organ weight, serum biochemical parameters and nutrient digestibility, and to determine the fate of the transgenic DNA in laying hens. A total of 144 50-week-old laying hens were grouped randomly into 2 treatments, with 8 replicates per treatment and 9 hens per replicate. Each treatment group of hens was fed with diets containing 62.4% non-transgenic conventional corn (CC) or PTC for 16 weeks. The phytase activity for CC was 37 FTU/kg of DM, whereas the phytase activity for PTC was 8,980 FTU/kg of DM. We observed that feeding PTC to laying hens had no adverse effect on organ weight or serum biochemical parameters (p>0.05). A fragment of a poultry-specific ovalbumin gene (ov) was amplified from all tissues of hens showing that the DNA preparations were amenable to PCR amplification. Neither the corn-specific invertase gene (ivr) nor the transgenic phyA2 gene was detected in the breast muscle, leg muscle, ovary, oviduct and eggs. The digestibility data revealed no significant differences between the hens that received the CC- and PTC-based diets in the digestibility of DM, energy, nitrogen and calcium (p>0.05). Phosphorus digestibility of hens fed the PTC-based diet was greater than that of hens fed the CC-based diet (58.03% vs 47.42%, p<0.01). Based on these results, it was concluded that the PTC had no deleterious effects on the organ weight or serum biochemical parameters of the laying hens. No recombinant phyA2 gene was detected in muscle tissues and reproductive organs of laying hens. The novel plant phytase was efficacious in improving the phosphorus digestibility of laying hens.


An energy tunable continuous 23S1 positronium beam.
We describe the experimental production of a beam of 23S1 positronium (Ps) atoms obtained from charge-exchange collisions between a positron beam and Xe held in a gas cell. The angular divergence of the emitted Ps beam was recorded using two position sensitive detectors located at different distances from the gas cell. The fraction of the Ps beam produced in the 23S1 level was measured via the change in the Ps count rate after driving the 23S1 → 23P2 transition with microwave radiation; with optimal experimental parameters, we estimate that up to 10% of the Ps beam is formed in the 23S1 state. The measured properties of the beam were used to evaluate the feasibility of using the system for precision spectroscopy of the n = 2 Ps fine structure using Ramsey interferometry.


Complete Genome Sequence of Turicibacter sp. Strain H121, Isolated from the Feces of a Contaminated Germ-Free Mouse.
Turicibacterbacteria are commonly detected in the gastrointestinal tracts and feces of humans and animals, but their phylogeny, ecological role, and pathogenic potential remain unclear. We present here the first complete genome sequence ofTuricibactersp. strain H121, which was isolated from the feces of a mouse line contaminated following germ-free derivation.


Advance Care Directive Preferences in Women Veterans: A Snapshot.
Prior research characterizes mainly male veteran preferences at end of life using the Veterans Administration Advance Directive (VA AD), there has been no specific studies focusing on women veteran's preferences concerning whether the AD is to be strictly (S) followed or to serve as a general guide (G). The purpose of this study was to describe women veteran preferences for life-sustaining treatments (LSTs) in various illness situations to assist providers in discussing end-of-life decisions. Additionally, we compared previously published LST preferences of male veterans with the study's sample. Using a descriptive retrospective approach, data was collected from 484 women veterans ADs between January 2010 and December 2019. Findings revealed that women tended to trend in the same direction as men, preferring to have advance directives serve as general guidance over being strictly followed. Unconscious/Coma/Vegetative was the only factor that was statistically significant for affecting the choice of following the AD.


Leading and trailing cells cooperate in collective migration of the zebrafish posterior lateral line primordium.
Collective migration of cells in the zebrafish posterior lateral line primordium (PLLp) along a path defined by Cxcl12a expression depends on Cxcr4b receptors in leading cells and on Cxcr7b in trailing cells. Cxcr7b-mediated degradation of Cxcl12a by trailing cells generates a local gradient of Cxcl12a that guides PLLp migration. Agent-based computer models were built to explore how a polarized response to Cxcl12a, mediated by Cxcr4b in leading cells and prevented by Cxcr7b in trailing cells, determines unidirectional migration of the PLLp. These chemokine signaling-based models effectively recapitulate many behaviors of the PLLp and provide potential explanations for the characteristic behaviors that emerge when the PLLp is severed by laser to generate leading and trailing fragments. As predicted by our models, the bilateral stretching of the leading fragment is lost when chemokine signaling is blocked in the PLLp. However, movement of the trailing fragment toward the leading cells, which was also thought to be chemokine dependent, persists. This suggested that a chemokine-independent mechanism, not accounted for in our models, is responsible for this behavior. Further investigation of trailing cell behavior shows that their movement toward leading cells depends on FGF signaling and it can be re-oriented by exogenous FGF sources. Together, our observations reveal the simple yet elegant manner in which leading and trailing cells coordinate migration; while leading cells steer PLLp migration by following chemokine cues, cells further back play follow-the-leader as they migrate toward FGFs produced by leading cells.


CT measurements of the proximal femoral medullary cavity in healthy adults: a cross-sectional study.
To analyse the proximal femoral morphology on three-dimensional reconstructed imagery to explore the factors influencing the relevant parameters. The cross-sectional study was conducted at Peking University Third Hospital in northern China from January 2019 to August 2020, and comprised healthy adults who underwent computed tomography scanning. Three-dimensional computed tomography reconstruction of the proximal femoral medullary cavity was performed using Mimics 22. The anatomical parameters related to total hip arthroplasty were measured to examine the relationship among gender, age and femoral length. Data was analysed using SPSS 20. Of the 63 adults, meaning 126 hips, 21(33.3%) were males, meaning 42 (33.3%) hips, and 42(66.6%) were females, meaning 84(66.6%) hips. The overall mean age was 51.5±23.1 years (range: 23-68 years). The inflection point of the medullary cavity curved at 5-10mm distal to the lesser trochanteric line. Most horizontal plane parameters significantly differed between men and women (p<0.05), with the mean medullary cavity being wider in men than women. There was a significant difference between the genders in the sagittal anterior-posterior diameter of the canal flare index (p<0.05). Age was negatively correlated with the coronal medial-lateral diameter and coronal lateral diameter of canal flare index. In the coronal and sagittal planes, there was a positive correlation between the metaphysis and diaphysis, and the coronal and sagittal planes were positively correlated with the orthogonal plane. Femoral morphology could be influenced by gender and age. Morphological changes of the proximal femoral medullary cavity were not present in a single plane, but were affected by multiple planes. When the diameter of one plane became larger, its orthogonal plane concomitantly increased.


Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution.
Patients with posterior cortical atrophy (PCA) often have Alzheimer disease (AD) at autopsy, yet are cognitively and anatomically distinct from patients with clinical AD. We sought to compare the distribution of β-amyloid and glucose metabolism in PCA and AD in vivo using Pittsburgh compound B (PiB) and FDG-PET. Patients with PCA (n = 12, age 57.5 ± 7.4, Mini-Mental State Examination [MMSE] 22.2 ± 5.1), AD (n = 14, age 58.8 ± 9.6, MMSE 23.8 ± 6.7), and cognitively normal controls (NC, n = 30, age 73.6 ± 6.4) underwent PiB and FDG-PET. Group differences in PiB distribution volume ratios (DVR, cerebellar reference) and FDG uptake (pons-averaged) were assessed on a voxel-wise basis and by comparing binding in regions of interest (ROIs). Compared to NC, both patients with AD and patients with PCA showed diffuse PiB uptake throughout frontal, temporoparietal, and occipital cortex (p < 0.0001). There were no regional differences in PiB binding between PCA and AD even after correcting for atrophy. FDG patterns in PCA and AD were distinct: while both groups showed hypometabolism compared to NC in temporoparietal cortex and precuneus/posterior cingulate, patients with PCA further showed hypometabolism in inferior occipitotemporal cortex compared to both NC and patients with AD (p < 0.05). Patients with AD did not show areas of relative hypometabolism compared to PCA. Fibrillar amyloid deposition in PCA is diffuse and similar to AD, while glucose hypometabolism extends more posteriorly into occipital cortex. Further studies are needed to determine the mechanisms of selective network degeneration in focal variants of AD.


Microscopic magnetic resonance elastography of traumatic brain injury model.
Traumatic brain injury (TBI) is a major cause of death and disability for which there is no cure. One of the issues inhibiting clinical trial success is the lack of targeting specific patient populations due to inconsistencies between clinical diagnostic tools and underlying pathophysiology. The development of reliable, noninvasive markers of TBI severity and injury mechanisms may better identify these populations, thereby improving clinical trial design. Magnetic resonance elastography (MRE), by assessing tissue mechanical properties, can potentially provide such marker. MRE synchronizes mechanical excitations with a phase contrast imaging pulse sequence to noninvasively register shear wave propagation, from which local values of tissue viscoelastic properties can be deduced. The working hypothesis of this study is that TBI involves a compression of brain tissue large enough to bring the material out of its elastic range, sufficiently altering mechanical properties to generate contrast on MRE measurements. To test this hypothesis, we combined microscopic MRE with brain tissue collected from adult male rats subjected to a controlled cortical impact injury. Measurements were made in different regions of interest (somatosensory cortex, hippocampus, and thalamus), and at different time points following the injury (immediate, 24 h, 7 days, 28 days). Values of stiffness in the somatosensory cortex were found to be 23-32% lower in the injured hemisphere than in the healthy one, when no significant difference was observed in the case of sham brains. A preliminary in vivo experiment is also presented, as well as alternatives to improve the faithfulness of stiffness recovery.


Attitudes and beliefs associated with leisure-time physical activity among African American adults.
More than 60% of African American adults do not meet recommendations for moderate physical activity. We sought to discover the extent to which health attitudes and beliefs are associated with leisure-time physical activity in this population. Cross-sectional study. African American adults were asked about their health attitudes and beliefs during a national survey. Participants were 807 African American men and women aged 18 years and older. Random-digit dialing was employed, sampling telephone numbers by geographical region, area code, and population size. Participants were asked six health belief questions on the importance of exercise and body weight in health. Logistic regression was used to determine which of these factors were associated with physical activity participation. The percent of respondents participating in some form of physical activity during the past month was 87.1% in men and 82.9% in women. Factors associated with previous month physical activity in men were perceived personal importance of exercise (P < .001) and necessity of exercise for health (P = .018). In women, perceived personal importance of exercise (P < .001), necessity of exercise for health (P = .006), and having enough activity space (P = .017) were associated with physical activity participation. Though the direction of causation is unknown, having the attitude that it is important to exercise or be physically active for health predicts physical activity participation in both African American men and women. Creating a sense of importance of physical activity to relieve stress and foster good health may stimulate physical activity participation in African American adults.


Why patients with heart failure die: hemodynamic and functional determinants of survival.
The high mortality of heart failure is associated with hemodynamic abnormalities, depressed cardiac function, and reduced exercise capacity. That these factors can be modified by drug treatment is of potential prognostic significance. Hemodynamic variables are related to survival, and long-term prognosis is better in patients with only midly abnormal cardiac output or ventricular filling pressures. Indexes of left ventricular function such as ejection or shortening fraction tend to be higher in patients who survive for longer periods. The relation between exercise capacity and survival, however, is unclear. Those patients with severe exercise intolerance (maximal oxygen uptake below 10 ml/min/kg) or with severe symptoms are at great risk of dying. However, exercise capacity and functional class are not related to prognosis when all classes of patients are considered together, especially if class IV patients are excluded. Most of the available data derive from retrospective analyses of trials involving heterogeneous patient populations and aimed at improving left ventricular performance or functional capacity. Large prospective trials aimed primarily at affecting mortality in a broad spectrum of patients are needed to learn more about determinants of survival in heart failure.


Biliary drainage method and temporal trends in patients admitted with cholangitis: a national audit.
In patients presenting with ascending cholangitis, better outcomes are reported in those undergoing endoscopic retrograde cholangiopancreatography (ERCP) compared with surgical drainage. To identify factors associated with the type of intervention, and to examine temporal trends in the treatment of ascending cholangitis. Data were extracted from the Nationwide Inpatient Sample. Patients ≥18 years of age with a diagnosis of cholangitis between 1998 and 2009 were selected. Temporal trends were assessed using Poisson regression models. Multivariable models were fitted to predict the likelihood of a patient undergoing ERCP, percutaneous or surgical drainage, or no drainage. A weighted estimate of 248,942 patients admitted for cholangitis was identified. Overall, 131,052 patients were treated with ERCP (52.6%), 10,486 with percutaneous drainage (4.2%) and 12,460 with surgical drainage (5.0%); 43.0% did not receive drainage during the admission. Temporal trends between 1998 and 2009 showed a decline in surgical and percutaneous drainage, and a rise in ERCP. In multivariable analyses adjusted for clustering, ERCP and percutaneous drainage were more often performed in institutions with a high volume of admissions for cholangitis, those with a greater bed number and hospitals located in urban areas. Over the past decade, the use of surgical and percutaneous drainage has decreased while that of ERCP has risen. Patients treated at institutions with a low volume of admissions for cholangitis, small bed number and in rural areas were less likely to undergo ERCP or percutaneous drainage.


Hepatoprotective role of Nicotiana plumbaginifolia Linn. against carbon tetrachloride-induced injuries.
Nicotiana plumbignifolia (Linn) is used as folk medicine in the treatment of liver dysfunction in Pakistan. The present study was designed to investigate the hepatoprotective role of N. plumbignifolia methanolice extract (NPME) against carbon tetrachloride (CCl4)-induced oxidative damage in liver of chicks. Methanolic extract of N. plumbignifolia was obtained and was further evaluated as a hepatoprotective agent against CCl4-induced oxidative damage in liver of chicks. For this study, 60-day-old 50 male chicks were divided into five groups. Chicks of group 1 (control) had free access to food and water. Group II received 1 mL/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route thrice a week for 4 weeks. Group III received 100 mg/kg body weight (b.w.) of silymarin via gavage after 48 h of CCl4 treatment, whereas group IV were given 200 mg/kg b.w. NPME after 48 h of CCl4 treatment. Hepatoprotective activity was assessed by measuring the activities of the antioxidant enzymes: catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)). Serum was analyzed for various biochemical parameters. The results revealed that CCl4 induced oxidative stress as evidenced by the significant decrease in the activity levels of antioxidant enzymes, while an increase in the levels of TBARS in liver samples is compared with the control group. Serum levels lactate dehydrogenase, triglycerides, total cholesterol, and low-density lipoprotein was elevated while reducing high-density lipoprotein compared to controls. Cotreatment of NPME treatment reversed these alterations, which seems likely that NPME can protect the liver tissues against CCl4-mediated oxidative damage.


Mycobacterium tuberculosis lacking all mycolic acid cyclopropanation is viable but highly attenuated and hyperinflammatory in mice.
Mycolic acids, the major lipid of the Mycobacterium tuberculosis cell wall, are modified by cyclopropane rings, methyl branches, and oxygenation through the action of eight S-adenosylmethionine (SAM)-dependent mycolic acid methyltransferases (MAMTs), encoded at four genetic loci. Mycolic acid modification has been shown to be important for M. tuberculosis pathogenesis, in part through effects on the inflammatory activity of trehalose dimycolate (cord factor). Studies using the MAMT inhibitor dioctylamine have suggested that the MAMT enzyme class is essential for M. tuberculosis viability. However, it is unknown whether a cyclopropane-deficient strain of M. tuberculosis would be viable and what the effect of cyclopropane deficiency on virulence would be. We addressed these questions by creating and characterizing M. tuberculosis strains lacking all functional MAMTs. Our results show that M. tuberculosis is viable either without cyclopropanation or without cyclopropanation and any oxygenated mycolates. Characterization of these strains revealed that MAMTs are required for acid fastness and resistance to detergent stress. Complete lack of cyclopropanation confers severe attenuation during the first week after aerosol infection of the mouse, whereas complete loss of MAMTs confers attenuation in the second week of infection. Characterization of immune responses to the cyclopropane- and MAMT-deficient strains indicated that the net effect of mycolate cyclopropanation is to dampen host immunity. Taken together, our findings establish the immunomodulatory function of the mycolic acid modification pathway in pathogenesis and buttress this enzyme class as an attractive target for antimycobacterial drug development.


Simultaneous Measurement and Distribution Analysis of Urinary Nicotine, Cotinine, Trans-3'-Hydroxycotinine, Nornicotine, Anabasine, and Total Nicotine Equivalents in a Large Korean Population.
Measurement of multiple nicotine metabolites and total nicotine equivalents (TNE) might be a more reliable strategy for tobacco exposure verification than measuring single urinary cotinine alone. We simultaneously measured nicotine, cotinine, 3-OH cotinine, nornicotine, and anabasine using 19,874 urine samples collected from the Korean National Health and Nutrition Examination Survey. Of all samples, 18.6% were positive for cotinine, 17.4% for nicotine, 17.3% for nornicotine, 17.6% for 3-OH cotinine, and 13.2% for anabasine. Of the cotinine negative samples, less than 0.3% were positive for all nicotine metabolites, but not for anabasine (5.7%). The agreement of the classification of smoking status by cotinine combined with nicotine metabolites was 0.982-0.994 (Cohen's kappa). TNE3 (the molar sum of urinary nicotine, cotinine, and 3-OH cotinine) was most strongly correlated with cotinine compared to the other nicotine metabolites; however, anabasine was less strongly correlated with other biomarkers. Among anabasine-positive samples, 30% were negative for nicotine or its metabolites, and 25% were undetectable. Our study shows that the single measurement of urinary cotinine is simple and has a comparable classification of smoking status to differentiate between current smokers and non-smokers relative to the measurement of multiple nicotine metabolites. However, measurement of multiple nicotine metabolites and TNE3 could be useful for monitoring exposure to low-level or secondhand smoke exposure and for determining individual differences in nicotine metabolism. Geometric or cultural factors should be considered for the differentiation of tobacco use from patients with nicotine replacement therapy by anabasine.


[Peculiarities of the action of protein positively reacting in the sedimentation test for cancer on the activity of glycolytic enzymes].
Blood serum of oncologic patients due to immunoglobulin involved in its composition, activates glycolysis in the soluble fraction of muscles when using starch, glycogen and glucose as substrates. The activation is registered under both aerobic and anaerobic conditions. When elucidating the immunoglobulin effect in a glycolytic chain under aerobic conditions it is shown that its activating effect in the incomplete incubation system is manifested with such glycolysis substrates as fructose-6-phosphate and 2-phosphoglyceric acid. Glycolysis activation with serum is insignificant or absent at all with the presence of glucose-6-phosphate, fructose-1,6-diphosphate, 3-phosphoglyceric aldehide, 3-phosphoglyceric acid, phosphoenolpyruvic acid, sodium pyruvate. Immunoglobulin isolated from the blood serum of oncologic patients does not affect the activity of purified preparations of hexokinase, glycerinaldehydephosphate dehydrogenase, lactate dehydrogenase under aerobic and anaerobic conditions. When using the air as a gas medium lactate dehydrogenase is activated by immunoglobulin. Lactate dehydrogenase activity under aerobic and anaerobic conditions is essentially lower than in the case when the air serves as a gas medium.


Anatomic Assessment of L1-S1 Neuroforaminal Dimensions Using Computed Tomography in 1,000 Patients: A Follow-Up Study.
While the radiographic criteria for diagnosing central lumbar stenosis are well described, criteria for diagnosing neuroforaminal stenosis (NFS) are unclear. Prior research has utilized magnetic resonance imaging (MRI) to characterize neuroforaminal dimensions (NFDs). However, this approach has inherent limitations that can adversely impact measurement accuracy. Existing literature on the use of computed tomography (CT) to investigate normal NFDs is limited. The purpose of the present study was to describe normal lumbar NFDs that would aid in the establishment of objective quantitative criteria for the diagnosis of NFS. This study evaluated CT imaging of 494 female and 506 male subjects between 18 and 35 years of age to determine normal NFDs, specifically the sagittal anteroposterior width, craniocaudal height, and area. Statistical analyses were performed to assess differences in NFDs according to variables including sex, height, weight, body mass index, and ethnicity. Without differentiating between sides or disc levels, mean NFDs were 8.71 mm for sagittal anteroposterior width, 17.73 mm for craniocaudal height, and 133.26 mm2 for area (n = 10,000 measurements each). Male subjects had larger NFDs than females at multiple levels. Asian and Caucasian subjects had larger NFDs than Hispanic and African American subjects at multiple levels. There were no associations between NFDs and anthropometric factors. The present study describes normal lumbar NFDs in young, healthy patients. NFDs were influenced by sex and ethnicity but not by anthropometric factors.


Factors influencing survival in head and neck patients with giant cervical lymph node metastasis.
Giant cervical lymph node metastasis originating from head and neck epidermoid carcinoma has traditionally indicated a poor prognosis. However, some patients with stage IV disease may live many years. In order to identify factors which might contribute to long-term survival, a retrospective analysis of 94 patients with head and neck squamous cell carcinoma and metastatic cervical lymph nodes greater than 4 cm was performed. At the time of study, 15 patients were alive; 62 of the remaining 79 patients had died due to related causes. Of the 15 survivors, mean survival time was 10.3 years, and the determinate five-year or greater survival rate was 20%. In contrast, mean survival of the 62 determinate nonsurvivors was 1.4 years. Recommended treatment for stage IV head and neck cancer patients with giant cervical lymph nodes consists of preoperative radiation therapy followed by wide-field en bloc resection.


N1s and O1s double ionization of the NO and N2O molecules.
Single-site N1s and O1s double core ionisation of the NO and N2O molecules has been studied using a magnetic bottle many-electron coincidence time-of-flight spectrometer at photon energies of 1100 eV and 1300 eV. The double core hole energies obtained for NO are 904.8 eV (N1s(-2)) and 1179.4 eV (O1s(-2)). The corresponding energies obtained for N2O are 896.9 eV (terminal N1s(-2)), 906.5 eV (central N1s(-2)), and 1174.1 eV (O1s(-2)). The ratio between the double and single ionisation energies are in all cases close or equal to 2.20. Large chemical shifts are observed in some cases which suggest that reorganisation of the electrons upon the double ionization is significant. Δ-self-consistent field and complete active space self-consistent field (CASSCF) calculations were performed for both molecules and they are in good agreement with these results. Auger spectra of N2O, associated with the decay of the terminal and central N1s(-2) as well as with the O1s(-2) dicationic states, were extracted showing the two electrons emitted as a result of filling the double core holes. The spectra, which are interpreted using CASSCF and complete active space configuration interaction calculations, show atomic-like character. The cross section ratio between double and single core hole creation was estimated as 1.6 × 10(-3) for nitrogen at 1100 eV and as 1.3 × 10(-3) for oxygen at 1300 eV.


Persistent renal damage following pre-eclampsia: a renal biopsy study of 13 patients.
Renal biopsy material was examined from 13 patients who had a history of pre-eclampsia and who were biopsied after delivery. The characteristic 'endotheliosis' associated with pre-eclampsia appeared to resolve at varying rates and was not seen in biopsies taken more than 1 month after delivery. Four of the biopsies showed residual focal segmental glomerular lesions which are described. Focal global glomerular sclerosis (eight biopsies), focal interstitial scarring (seven biopsies) and arteriolo-sclerosis (nine biopsies) were also identified. These findings support those earlier reports which indicated that pre-eclampsia is capable of producing persistent renal damage in a small but significant percentage of cases.


Sub-oxycline methane oxidation can fully uptake CH4 produced in sediments: case study of a lake in Siberia.
It is commonly assumed that methane (CH4) released by lakes into the atmosphere is mainly produced in anoxic sediment and transported by diffusion or ebullition through the water column to the surface of the lake. In contrast to that prevailing idea, it has been gradually established that the epilimnetic CH4 does not originate exclusively from sediments but is also locally produced or laterally transported from the littoral zone. Therefore, CH4 cycling in the epilimnion and the hypolimnion might not be as closely linked as previously thought. We utilized a high-resolution method used to determine dissolved CH4 concentration to analyze a Siberian lake in which epilimnetic and hypolimnetic CH4 cycles were fully segregated by a section of the water column where CH4 was not detected. This layer, with no detected CH4, was well below the oxycline and the photic zone and thus assumed to be anaerobic. However, on the basis of a diffusion-reaction model, molecular biology, and stable isotope analyses, we determined that this layer takes up all the CH4 produced in the sediments and the deepest section of the hypolimnion. We concluded that there was no CH4 exchange between the hypolimnion (dominated by methanotrophy and methanogenesis) and the epilimnion (dominated by methane lateral transport and/or oxic production), resulting in a vertically segregated lake internal CH4 cycle.


Resource partitioning between ungulate populations in arid environments.
Herbivores are major drivers of ecosystem structure, diversity, and function. Resilient ecosystems therefore require viable herbivore populations in a sustainable balance with environmental resource availability. This balance is becoming harder to achieve, with increasingly threatened species reliant on small protected areas in increasingly harsh and unpredictable environments. Arid environments in North Africa exemplify this situation, featuring a biologically distinct species assemblage exposed to extreme and volatile conditions, including habitat loss and climate change-associated threats. Here, we implement an integrated likelihood approach to relate scimitar-horned oryx (Oryx dammah) and dorcas gazelle (Gazella dorcas) density, via dung distance sampling, to habitat, predator, and geographic correlates in Dghoumes National Park, Tunisia. We show how two threatened sympatric ungulates partition resources on the habitat axis, exhibiting nonuniform responses to the same vegetation gradient. Scimitar-horned oryx were positively associated with plant species richness, selecting for vegetated ephemeral watercourses (wadis) dominated by herbaceous cover. Conversely, dorcas gazelle were negatively associated with vegetation density (herbaceous height, litter cover, and herbaceous cover), selecting instead for rocky plains with sparse vegetation. We suggest that adequate plant species richness should be a prerequisite for areas proposed for future ungulate reintroductions in arid and semi-arid environments. This evidence will inform adaptive management of reintroduced ungulates in protected environments, helping managers and planners design sustainable ecosystems and effective conservation programs.


The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release.
Humans carrying the CORD7 (cone-rod dystrophy 7) mutation possess increased verbal IQ and working memory. This autosomal dominant syndrome is caused by the single-amino acid R844H exchange (human numbering) located in the 310 helix of the C2A domain of RIMS1/RIM1 (Rab3-interacting molecule 1). RIM is an evolutionarily conserved multi-domain protein and essential component of presynaptic active zones, which is centrally involved in fast, Ca2+-triggered neurotransmitter release. How the CORD7 mutation affects synaptic function has remained unclear thus far. Here, we established Drosophila melanogaster as a disease model for clarifying the effects of the CORD7 mutation on RIM function and synaptic vesicle release. To this end, using protein expression and X-ray crystallography, we solved the molecular structure of the Drosophila C2A domain at 1.92 Å resolution and by comparison to its mammalian homologue ascertained that the location of the CORD7 mutation is structurally conserved in fly RIM. Further, CRISPR/Cas9-assisted genomic engineering was employed for the generation of rim alleles encoding the R915H CORD7 exchange or R915E, R916E substitutions (fly numbering) to effect local charge reversal at the 310 helix. Through electrophysiological characterization by two-electrode voltage clamp and focal recordings we determined that the CORD7 mutation exerts a semi-dominant rather than a dominant effect on synaptic transmission resulting in faster, more efficient synaptic release and increased size of the readily releasable pool but decreased sensitivity for the fast calcium chelator BAPTA. In addition, the rim CORD7 allele increased the number of presynaptic active zones but left their nanoscopic organization unperturbed as revealed by super-resolution microscopy of the presynaptic scaffold protein Bruchpilot/ELKS/CAST. We conclude that the CORD7 mutation leads to tighter release coupling, an increased readily releasable pool size and more release sites thereby promoting more efficient synaptic transmitter release. These results strongly suggest that similar mechanisms may underlie the CORD7 disease phenotype in patients and that enhanced synaptic transmission may contribute to their increased cognitive abilities.


Cell Surface Properties of Lactococcus lactis Reveal Milk Protein Binding Specifically Evolved in Dairy Isolates.
Surface properties of bacteria are determined by the molecular composition of the cell wall and they are important for interactions of cells with their environment. Well-known examples of bacterial interactions with surfaces are biofilm formation and the fermentation of solid materials like food and feed. Lactococcus lactis is broadly used for the fermentation of cheese and buttermilk and it is primarily isolated from either plant material or the dairy environment. In this study, we characterized surface hydrophobicity, charge, emulsification properties, and the attachment to milk proteins of 55 L. lactis strains in stationary and exponential growth phases. The attachment to milk protein was assessed through a newly developed flow cytometry-based protocol. Besides finding a high degree of biodiversity, phenotype-genotype matching allowed the identification of candidate genes involved in the modification of the cell surface. Overexpression and gene deletion analysis allowed to verify the predictions for three identified proteins that altered surface hydrophobicity and attachment of milk proteins. The data also showed that lactococci isolated from a dairy environment bind higher amounts of milk proteins when compared to plant isolates. It remains to be determined whether the alteration of surface properties also has potential to alter starter culture functionalities.


[Glucose-6-phosphate dehydrogenase deficiency, neonatal hyperbilirubinemia and Gilbert syndrome].
The aim of this work was to evaluate the influence of abnormal UDP-glucoronosyltransferase-1 (UGT1A1) gene variant, on the incidence and severity of neonatal hyperbilirubinemia, in glucose-6-phosphate dehydrogenase (G6PD) deficient newborns. The A(TA)nTAA region in the promoter of the UGT1A1 gene was analysed in 20 children with G6PD deficiency. Fourteen of these children had the African type variant (G6PDA-) and 6 had different variants (G6PDNara, G6PDGuadalajara, G6PDDurham, G6PDTomah, G6PDAveiro e G6PDNashville) related to chronic nonspherocytic haemolytic anaemia (CNSHA). The existence of a positive history of neonatal hyperbilirubinemia, as well as its severity was registered. The incidence of neonatal hyperbilirubinemia was increased in this group of children (90%) and was not associated with abnormal alleles of the UGT1A1 gene. It was not possible to assess the influence of abnormal alleles in the severity of the neonatal hyperbilirubinemia. However, these abnormal alleles did not account for the severity of jaundice in children who presented variants related to CNSHA, since 5 were treated with an exchange transfusion and none presented abnormal alleles.


Complete Dehydrogenation of Hydrazine Borane on Manganese Oxide Nanorod-Supported Ni@Ir Core-Shell Nanoparticles.
Hydrazine borane (HB; N2H4BH3) has been considered to be one of the most promising solid chemical hydrogen storage materials owing to its high hydrogen capacity and stability under ambient conditions. Despite that, the high purity of hydrogen production from the complete dehydrogenation of HB stands as a major problem that needs to be solved for the convenient use of HB in on-demand hydrogen production systems. In this study, we describe the development of a new catalytic material comprised of bimetallic Ni@Ir core-shell nanoparticles (NPs) supported on OMS-2-type manganese oxide octahedral molecular sieve nanorods (Ni@Ir/OMS-2), which can reproducibly be prepared by following a synthesis protocol including (i) the oleylamine-mediated preparation of colloidal Ni@Ir NPs and (ii) wet impregnation of these ex situ synthesized Ni@Ir NPs onto the OMS-2 surface. The characterization of Ni@Ir/OMS-2 has been done by using various spectroscopic and visualization techniques, and their results have revealed the formation of well-dispersed Ni@Ir core-shell NPs on the surface of OMS-2. The catalytic employment of Ni@Ir/OMS-2 in the dehydrogenation of HB showed that firstname.lastname@example.com/OMS-2 exhibited high dehydrogenation selectivity (>99%) at complete conversion with a turnover frequency (TOF) value of 2590 h-1 at 323 K, which is the highest activity value among all reported catalysts for the complete dehydrogenation of HB. Furthermore, the firstname.lastname@example.com/OMS-2 catalyst enables facile recovery and high stability against agglomeration and leaching, which make it a reusable catalyst in the complete dehydrogenation of HB. The studies reported herein also include the collection of wealthy kinetic data to determine the activation parameters for firstname.lastname@example.com/OMS-2-catalyzed dehydrogenation of HB.


General practitioner management related to skin cancer prevention and screening during standard medical encounters: a French cross-sectional study based on the International Classification of Primary Care.
The aim of this study was to assess general practitioner (GP) management practices related to skin cancer prevention and screening during standard medical encounters. Data on medical encounters addressing skin cancer issues were obtained from a French database containing information from 17 019 standard primary care consultations. Data were collected between December 2011 and April 2012 by 54 trainees who reported the regular practice of 128 GPs using the International Classification of Primary Care. Reasons for encounters and the following care processes were recorded: counselling, clinical examinations and referral to a specialist. Medical encounters addressing skin cancer issues were compared with medical encounters that addressed other health problems using a multivariate analysis. Only 0.7% of medical encounters addressed skin cancer issues. When patients did require management of a skin cancer-related issue, this was more likely initiated by the doctor than the patient (70.7% vs 29.3%; p<0.001). Compared with medical encounters addressing other health problems, encounters that addressed skin cancer problems required more tasks (3.7 vs 2.5; p<0.001) and lasted 1 min and 20 s longer (p=0.003). GPs were less involved in clinical examinations (67.5% vs 97.1%; p<0.001), both complete (7.3% vs 22.3%, p<0.001) and partial examinations (60.2% vs 74.9%), and were less involved in counselling (5.7% vs 16.9%; p<0.001). Patients presenting skin cancer issues were referred to a specialist more often than patients consulting for other health problems (39.0% vs 12.1%; p<0.001). GPs performed a biopsy in 6.7% of all skin cancer-related encounters. This study demonstrates discrepancies between the high prevalence of skin cancer and the low rate of medical encounters addressing these issues in general practice. Our findings should be followed by qualitative interviews to better understand the observed practices in this field.


Sources of error in direct radionuclide cystography in children and the need for a standardized, manometric apparatus.
Direct radionuclide cystography (DRC) is a safe and reliable method for the detection and follow-up of vesico-ureteral reflux (VUR). Since the first DRC was performed, during the early 60s, the method has undergone many refinements. Themanometric approach, which was first introduced in 1984, provides a correlation between the bladder pressure and VUR visualization. In this study the sources of error that may alter the results of DRC are discussed and a novel, standardized low costmanometric apparatus is suggested.


Moiré technique for spatial coherence measurements of soft-x-ray lasers.
We present a novel moiré diagnostic that allows the time-averaged spatial coherence properties of soft-x-ray lasers to be measured. The technique is an extension of the theoretical work in a recent paper [J. Opt. Soc. Am. A 16, 323 (1999)] and is based on the concept of decompositions of the far-field divergence for partially coherent beams. An appealing feature of the approach is that the spatial coherence width at other planes can be evaluated from the measured one at a given plane on the assumption of shape-invariant beams.


Full-face laser resurfacing using a supplemented topical anesthesia protocol.
Laser resurfacing has become a popular modality for the treatment of photodamaged skin, rhytids, and acne scarring. In many cases, this procedure is performed under general anesthesia or intravenous sedation in conjunction with nerve blocks and local infiltration. To evaluate the safety and efficacy of facial carbon dioxide laser resurfacing using a supplemented topical anesthesia protocol. Nonrandomized case series of patients observed for 1 year. Outpatient surgery center. Two hundred consecutive patients undergoing treatment for facial rhytids or acne scarring. Intervention Full-face carbon dioxide laser resurfacing procedures were performed using a supplemented topical anesthesia protocol. Pretreatment medications included diazepam, oral analgesics, and intramuscular ketorolac tromethamine. Tolerability of procedure, healing times, and adverse effects. Topical anesthesia provided effective and sufficient anesthesia in most cases. Only 10 of 200 patients required additional anesthesia (regional nerve blocks and/or local infiltration). Substantial improvement of rhytids, photodamage, and acne scarring was observed. Posttreatment hypopigmentation was seen in 1 patient. Scarring was not observed. Conclusion A supplemented topical anesthesia protocol for full-face laser resurfacing is a safe and effective alternative to traditional anesthesia strategies.


Ceramidase activity in bacterial skin flora as a possible cause of ceramide deficiency in atopic dermatitis.
A marked decrease in the content of ceramide has been reported in the horny layer of the epidermis in atopic dermatitis (AD). This decrease impairs the permeability barrier of the epidermis, resulting in the characteristic dry and easily antigen-permeable skin of AD, since ceramide serves as the major water-holding molecule in the extracellular space of the horny layer. On the other hand, the skin of such patients is frequently colonized by bacteria, most typically by Staphylococcus aureus, possessing genes such as those for sphingomyelinase, which are related to sphingolipid metabolism. We therefore tried to identify a possible correlation between the ceramide content and the bacterial flora obtained from the skin of 25 patients with AD versus that of 24 healthy subjects, using a thin-layer chromatographic assay of the sphingomyelin-associated enzyme activities secreted from the bacteria. The findings of the assay demonstrated that ceramidase, which breaks ceramide down into sphingosine and fatty acid, was secreted significantly more from the bacterial flora obtained from both the lesional and the nonlesional skin of patients with AD than from the skin of healthy subjects; sphingomyelinase, which breaks sphingomyelin down into ceramide and phosphorylcholine, was secreted from the bacterial flora obtained from all types of skin at similar levels for the patients with AD and the healthy controls. The finding that the skin of patients with AD is colonized by ceramidase-secreting bacteria thus suggests that microorganisms are related to the deficiency of ceramide in the horny layer of the epidermis, which increases the hypersensitivity of skin in AD patients by impairing the permeability barrier.


Cu(i) complex bearing a PNP-pincer-type phosphaalkene ligand with a bulky fused-ring Eind group: properties and applications to FLP-type bond activation and catalytic CO2 reduction.
Herein, we report the synthesis of [Cu(Eind2-BPEP)][PF6] (2) (Eind2-BPEP = 2,6-bis(2-Eind-2-phosphaethenyl)pyridine, Eind = 1,1,3,3,5,5,7,7-octaethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl), a three-coordinated Cu(i) complex bearing a PNP-pincer-type phosphaalkene ligand with bulky fused-ring Eind groups. The Gutmann-Beckett test revealed that complex 2 is highly Lewis acidic and comparable in strength to B(C6F5)3, which is a relatively strong Lewis acid. In addition, 2 is more Lewis acidic than [Cu(Mes*2-BPEP)][PF6] (3), the analogous complex with less-bulky Mes* instead of Eind groups. DFT calculations using model compounds revealed that the higher Lewis acidity of 2 compared to 3 is not due to the electronic effects of the ligand, but due to a reduction in the LUMO energy caused by the steric effect of the bulky Eind groups. When combined with a tertiary amine, the highly Lewis acidic and bulky 2 exhibits the reactivity of a frustrated Lewis pair (FLP) and can activate hydrogen and phenylacetylene. Complexes 2 and 3 were found to catalyze the hydrogenation and hydrosilylation of CO2 in the presence of DBU under relatively mild conditions.


Practical approaches to pedagogically rich online tutorials in health professions education.
Health professions education in tertiary, industrial and other contexts often entails face-to-face small group learning through tutorials. The current novel coronavirus, COVID-19, has reduced face-to-face contact, and this has challenged how health professionals and clinical students can access training, accreditation and development. Online and other remote mechanisms are available to tutors and course designers; however, they might not feel comfortable with such affordances, in light of expectations to so rapidly change familiar teaching and delivery styles. This may result in the loss of interaction and disruption of peer learning, which are hallmarks of the small group tutorial. Collaborative learning is essential to develop and refine an emerging sense of belonging to a professional community through formal studies, and interactive learning is a requirement for some registered health professions to satisfy ongoing professional accreditation. Online media has been used to promote social learning in regional, rural and remote communities for some time. Strategies for learning activity design and tutor training are proposed to equip course designers and educators to support health professions education remotely, through the synchronous, online small group. This may herald a new era of increased access to training and professional development for non-urban learners, beyond COVID-19.


Anaesthetic management of acute blunt thoracic trauma.
Sunnybrook Health Science Centre is an adult regional trauma unit serving metropolitan Toronto and environs. We undertook a two-year retrospective review of patients admitted to our institution with blunt thoracic trauma. Three hundred and thirty-three patients with blunt trauma and an injury severity score (ISS) greater than 17 required emergency surgery. Of these, 208 had blunt thoracic injuries while 125 did not have chest injuries. Both groups were similar with respect to age but patients with thoracic trauma had a greater ISS. (P less than 0.05) and greater intraoperative mortality (P less than 0.01). The aetiology of the intraoperative deaths with one exception was exsanguination. Emergency thoracotomy or sternotomy indicated a poor prognosis with a mortality rate of 80%. The most common intraoperative problem was an elevated airway pressure. Awake intubation was undertaken in 77.5% of patients requiring anaesthesia and surgery because of the potentially compromised airways and difficult intubations due to the nature of the associated injuries. Finally, 74% of patients undergoing urgent surgery required mechanical postoperative ventilation. The presence of blunt chest trauma should be considered a marker of the severity of injury sustained by the patient.


[Permanent education in an outsourced cleaning service at a university hospital].
Permanent education has been a source of constant reflections due to a rapid technological evolution, which brings about changes in work organization, and requires updated knowledge from workers. In the context of this new technological paradigm in production relations and work organization, we analyzed the permanent education activities involving outsourced workers in the cleaning sector of a university hospital and evaluated their knowledge about work environment contamination risks and the importance of their work for health maintenance. Six semi-structured interviews were carried out with the outsourced workers in the cleaning sector and two with the persons in charge of permanent education for these workers, besides four activity observation periods and the field diary. All workers considered permanent education essential because they had no previous experience in relation to hospital cleaning.


Preterm Infant Outcomes Following COVID-19 Lockdowns in Melbourne, Australia.
Background Community lockdowns during the coronavirus disease 2019 (COVID-19) pandemic may influence preterm birth rates, but mechanisms are unclear. Methods We compared neonatal outcomes of preterm infants born to mothers exposed to community lockdowns in 2020 (exposed group) to those born in 2019 (control group). Main outcome studied was composite of significant neonatal morbidity or death. Results Median gestational age was 35 + 4 weeks (295 infants, exposed group) vs. 35 + 0 weeks (347 infants, control group) (p = 0.108). The main outcome occurred in 36/295 (12.2%) infants in exposed group vs. 46/347 (13.3%) in control group (p = 0.69). Continuous positive airway pressure (CPAP) use, jaundice requiring phototherapy, hypoglycaemia requiring treatment, early neonatal white cell and neutrophil counts were significantly reduced in the exposed group. Conclusions COVID-19 community lockdowns did not alter composite neonatal outcomes in preterm infants, but reduced rates of some common outcomes as well as early neonatal inflammatory markers.


Leiomyosarcoma of the spermatic cord with scalp metastasis: case report and literature review.
Herein we present 82-year-old man with leiomyosarcoma arising from the spermatic cord with scalp metastasis, five years after primary surgical treatment. Complete surgical excision is required in such cases, as well as precise evaluation of further therapy. Paratesticular leiomyosarcoma is a rare entity, malignant mesenchimal tumor of smooth muscle differentiation. Although leiomyosarcomas of different localizations have well-known metastatic potential, cutaneous metastases are extremely rare with only 16 cases described in the literature. To our knowledge there are no reported cases of the paratesticular leiomyosarcoma metastatic to the skin. This article reviews the literature regarding paratesticular leiomyosarcoma presentation, diagnosis and treatment.


Glycemic control in patients undergoing coronary artery bypass graft surgery: Clinical features, predictors, and outcomes.
Critically ill patients with hyperglycemia have worse prognosis. The degree to which glycemic control is achieved following CABG surgery and the association with clinical outcomes is not well understood. We studied patients undergoing higher risk CABG surgery at 55 US hospitals. Good glycemic control was defined as 70-180mg/dL in the first 24h postoperatively. Generalized estimating equations logistic regression models were used to assess the relationship between glycemic control and clinical outcomes after adjusting for baseline characteristics. Among 2032 patients only 297 (15%) had good glycemic control in the perioperative period, with 2% having at least one BS below 70, 63% having at least one BS above 180, and 9% having both. Patients with good glycemic control had lower rates of the risk-adjusted composite outcome of mortality and major complications (OR=0.66; 95% CI 0.46-0.93, p=0.02). Hypoglycemic events occurred in 250 (12%) patients, ranging among hospitals from 2% to 58%, p<0.001 and was not associated with hospitals' overall rate of good glucose control. Achieving glycemic control following high risk CABG was associated with lower operative mortality and morbidity, yet achieved in only 15% of patients. Hospitals varied considerably in their ability to achieve good glycemic control.


Developmental Pathoconnectomics and Advanced Fetal MRI.
Developmental pathoconnectomics is an emerging field that aims to unravel the events leading to and outcome from disrupted brain connectivity development. Advanced magnetic resonance imaging (MRI) technology enables the portrayal of human brain connectivity before birth and has the potential to offer novel insights into normal and pathological human brain development. This review gives an overview of the currently used MRI techniques for connectomic imaging, with a particular focus on recent studies that have successfully translated these to the in utero or postmortem fetal setting. Possible mechanisms of how pathologies, maternal, or environmental factors may interfere with the emergence of the connectome are considered. The review highlights the importance of advanced image post processing and the need for reproducibility studies for connectomic imaging. Further work and novel data-sharing efforts would be required to validate or disprove recent observations from in utero connectomic studies, which are typically limited by low case numbers and high data drop out. Novel knowledge with regard to the ontogenesis, architecture, and temporal dynamics of the human brain connectome would lead to the more precise understanding of the etiological background of neurodevelopmental and mental disorders. To achieve this goal, this review considers the growing evidence from advanced fetal connectomic imaging for the increased vulnerability of the human brain during late gestation for pathologies that might lead to impaired connectome development and subsequently interfere with the development of neural substrates serving higher cognition.


High-frequency ultrasound imaging to assess fetal pancreas: a promising application.
Objectives: The purpose of this study is to establish a comprehensive reference range of quantitative characteristics of the fetal pancreas using a high-frequency transducer, and assess the growth and development of the fetal pancreas.Methods: Pregnant women referred to a tertiary center were recruited to undergo a detailed fetal scan from 16 to 37 weeks. We evaluated the visualization rate of the fetal pancreas with high-frequency and low-frequency transducers and measured the head, neck, body, tail, circumference, area, and abdominal circumference(AC) of the fetal pancreas at different gestational ages(GA) with the high-frequency transducer. Regression analysis was used to analyze the relationship between biological parameters and GA and AC.Results: During the time periods of 16+1∼21+6 weeks and 22+1∼27+6 weeks, the visualization rate of high-frequency transducers was higher compared to low-frequency transducers (83.33% vs 45% and 95.65% vs 70%, respectively). However, in the third trimester of pregnancy, the performance of the two transducers was similar (70.37% vs 74.07% for 28+1∼33+6 weeks and 41.67% vs 53.85% for 34+1∼37+6 weeks). The head, neck, body, and tail as well as the circumference and area of the pancreas were significantly positively correlated with GA (R2=0.87, 0.94, 0.92, 0.92,0.96, and 0.92) and AC (R2=0.87, 0.93, 0.91, 0.93,0.96, and 0.92).Conclusions: The high-frequency transducer was utilized to establish the normal reference, which can be used to evaluate normal pancreatic development and may help in the accurate diagnosis of fetal pancreatic abnormalities.


The Temporal Effect of Uncertain Context on the Perceptual Processing of Painful and Non-Painful Stimulation.
Uncertainty has been demonstrated to influence the perception of noxious stimuli, but little is known about the effects of prolonged uncertain contexts on the perception of painful and non-painful stimuli. To address this knowledge gap, the present study utilized a cue-based NPU-threat task, where uncertain and certain trials were separated into distinct blocks. The objective was to investigate the impact of uncertain contexts on the temporal dynamics of electroencephalogram (EEG) activity during the processing of painful and non-painful stimuli. The results revealed that the influence of uncertain contexts on neural responses extends beyond painful trials and is also evident in non-painful trials. In uncertain contexts, it has been observed that painful stimuli elicit larger P2 amplitudes and late beta band (13-30Hz) event-related desynchronization (ERD) around 500-700 ms. However, in certain contexts, painful stimuli evoke stronger late gamma band (50-70Hz) event-related synchronization (ERS) around 600-700 ms. For non-painful trials, in uncertain contexts, significantly higher amplitudes of the late positive potential (LPP) component and delta-theta band (2-7Hz) ERS were observed compared to certain non-painful stimuli. These findings demonstrate that uncertain contexts exert a significant impact on the processing of both painful and non-painful stimuli, and this influence is mediated by distinct neural mechanisms.


Transvenous Renal Transplant Biopsy via a Transfemoral Approach.
Percutaneous renal biopsy (PRB) of kidney transplants might be prevented by an elevated risk of bleeding or limited access to the allograft. In the following, we describe our initial experience with 71 transvenous renal transplant biopsies in 53 consecutive patients with unexplained reduced graft function who were considered unsuitable candidates for PRB (4.2% of all renal transplant biopsies at our institution). Biopsies were performed via the ipsilateral femoral vein with a renal biopsy set designed for transjugular renal biopsy (TJRB) of native kidneys. Positioning of the biopsy system within the transplant vein was achievable in 58 of 71 (81.7%) procedures. The specimen contained a median of 10 glomeruli (range 0-38). Tissue was considered as adequate for diagnosis in 56 of 57 (98.2%) biopsies. With respect to BANFF 50.9% of the specimen were adequate (>10 glomeruli), 47.4% marginally adequate (1-9 glomeruli) and 1.8% inadequate (no glomeruli). After implementation of real-time assessment all specimen contained glomeruli. One of the fifty-eight (1.8%) procedure-related major complications occurred (hydronephrosis requiring nephrostomy due to gross hematuria). Transfemoral renal transplant biopsy (TFRTB) is feasible and appears to be safe compared to PRB. It offers a useful new alternative for histological evaluation of graft dysfunction in selected patients with contraindications to PRB.


An update on immunologic mechanisms in the respiratory mucosa in response to air pollutants.
Every day, we breathe in more than 10,000 L of air that contains a variety of air pollutants that can pose negative consequences to lung health. The respiratory mucosa formed by the airway epithelium is the first point of contact for air pollution in the lung, functioning as a mechanical and immunologic barrier. Under normal circumstances, airway epithelial cells connected by tight junctions secrete mucus, airway surface lining fluid, host defense peptides, and antioxidants and express innate immune pattern recognition receptors to respond to inhaled foreign substances and pathogens. Under conditions of air pollution exposure, the defenses of the airway epithelium are compromised by reductions in barrier function, impaired host defense to pathogens, and exaggerated inflammatory responses. Central to the mechanical and immunologic changes induced by air pollution are activation of redox-sensitive pathways and a role for antioxidants in normalizing these negative effects. Genetic variants in genes important in epithelial cell function and phenotype contribute to a diversity of responses to air pollution in the population at the individual and group levels and suggest a need for personalized approaches to attenuate the respiratory mucosal immune responses to air pollution.


The general practice formulary--its role in rational therapeutics.
This paper describes a project in which a voluntary preferred prescribing list (general practice formulary), analogous to those already in use in some hospitals, was created, implemented and monitored. Cooperation between a pharmacist with knowledge of drug information, access to specialist advice and back-up in the form of evaluated information from drug information centres and a group of five general practitioners and their trainees was necessary.The formulary was well accepted with between 68.2% and 89.6% compliance in therapeutic classes corresponding to the recent National Health Service restricted groups. This method enhances the critical appraisal of prescribing rationale, takes into account the needs of doctors and patients, and reduces costs. Such work highlights the value and scope of interdisciplinary liaison between pharmacists, general practitioners and clinical pharmacologists and it could prove beneficial on a national scale.


Lactitol, a new hydrogenated lactose derivative: intestinal absorption and laxative threshold in normal human subjects.
In the first part of the study, the absorption of lactitol, a new disaccharide analogue of lactose, was studied using an in vivo jejunal perfusion technique in man. Intestinal uptake of lactitol from isotonic solutions containing 10, 30, 60, and 100 mmol lactitol/l was insignificant. In the second part of the study the laxative threshold of lactitol was determined and compared with that of sorbitol in a double-blind, randomized, cross-over study on twenty-one normal subjects. Laxative threshold was considered to be either the maximum dose tolerated without unacceptable diarrhoea or gastrointestinal side effects, or when the maximum dose in the study was reached. Increasing amounts of lactitol, sorbitol or placebo were administered in two divided doses each day until subjects developed diarrhoea or severe gastrointestinal side effects. The laxative threshold of lactitol (74 (SE 5) g/d) was similar to that of sorbitol (71 (SE 5) g/d). These findings indicate that lactitol is not absorbed by the human small intestine. Although diarrhoea or other gastrointestinal side effects occurred as the dose was increased, 40 g lactitol/d was well tolerated.


Short-term fasting suppresses leptin and (conversely) activates disorderly growth hormone secretion in midluteal phase women--a clinical research center study.
Short term fasting activates the corticotropic and somatotropic, and suppresses the reproductive, axis in men. Analogous neuroendocrine responses are less well characterized in women. Recently, we identified a negative association between the adipocyte-derived nutritional signaling peptide, leptin, and pulsatile GH secretion in older fed women. In the present study, we investigated the impact of acute nutrient deprivation on pulsatile GH and LH secretion and mean leptin concentrations in eight healthy young women in the sex-steroid replete milieu of the midluteal phase of the normal menstrual cycle. Volunteers underwent 24-h blood sampling during randomly ordered, short term (2.5-day), fasting vs. fed sessions in separate menstrual cycles. Pulsatile GH and LH secretion over 24 h was quantified by deconvolution analysis, nyctohemeral rhythmicity was quantified by cosinor analysis, and the orderliness of the GH or LH release process was quantified by the approximate entropy statistic. By paired statistical analysis, a 2.5-day fast failed to alter mean (pooled) 24-h serum concentrations of LH, progesterone, estradiol, or PRL, but increased cortisol levels more than 1.5-fold (P = 0.0003). Concurrently, mean (pooled) serum leptin concentrations fell by 75% (P = 0.0003), and insulin-like growth factor I (IGF-I; P < 0.05) and insulin decreased significantly (P = 0.0018). In contrast, the daily pulsatile GH secretion rate rose 3-fold (P < 0.001). Amplified daily GH secretion was attributable mechanistically to a 2.3-fold rise in GH secretory burst mass, reflecting an increased GH secretory burst amplitude (P < 0.01). The GH half-life, duration of GH secretory bursts, and GH pulse frequency did not vary during short term fasting. The disorderliness of GH release increased significantly with nutrient restriction (P = 0.005). The mesor and amplitude of the nyctohemeral serum GH concentration rhythm also rose with fasting (P < 0.01), but the timing of maximal serum GH concentrations did not change. Thus, short-term (2.5-day) fasting during the sex steroid-replete midluteal phase of the menstrual cycle in healthy young women profoundly suppresses 24-h serum leptin and insulin (and to a lesser degree, IGF-I) concentrations, augments cortisol release, but fails to alter daily LH, estradiol, or progesterone concentrations. In contrast, the GH axis exhibits strikingly amplified pulsatile secretion, increased nyctohemeral rhythmicity, and marked disorderliness of the release process. We conclude that the somatotropic axis is more evidently vulnerable to short-term nutrient restriction than the reproductive axis in steroidogenically sufficient midluteal phase women. This study invites the question of whether normal (nutritionally replete) GH secretory dynamics can be restored in fasting women by human leptin, insulin, or IGF-I infusions.


Neck Circumference and its Correlation to Other Anthropometric Parameters and Finnish Diabetes Risk Score (FINDRISC).
The Neck Circumference (NC) is an anthropometric measure to evaluate obesity. The FINDRISC predicts the risk of developing type 2 diabetes mellitus. Our aims were to identify the mean value of NC in individuals with higher (≥15 points) and lower FINDRISC and to establish cutoff values that indicate individuals with higher FINDRISC. It is a population-based, cross-sectional study representative of the city of Curitiba, Brazil. We studied individuals (>18 years), without diabetes mellitus, between August 2013 and August 2014. We evaluated anthropometric parameters, glycaemia, socioeconomic situation, chronic conditions, and their risk factors. In a sex-specific analysis, data are presented as mean and standard deviation. We performed Pearson's and Spearman's correlation between NC and the waist circumference, body mass index and FINDRISC. Receiver Operating Characteristic curves were estimated for NC and higher FINDRISC. Logistic regression models were built to analyze the association between higher FINDRISC and 1-SD increase in NC. We studied 950 individuals (621 women) with a mean age of 47.4 ± 17.6 years and body mass index of 26.2 ± 5.6 kg/m2. The mean NCs were 34.1 ± 3.1 cm in women and 38.2 ± 3.5 cm in men. Mean NC was lower in women (33.7 ± 2.9 cm vs. 35.8 ± 3.2 cm) and men (37.7 ± 3.4 cm vs. 41 ± 3.6 cm) with lower FINDRISC (p <0.001). All the correlations with NC were significant (p ≤ 0.001). The area under the curve for NC and the higher FINDRISC was 0.702 (95% CI 0.653 - 0.752) for women and 0.762 for men (95% CI 0.679 - 0.845), determining the best cutoff value of 34.5 cm for women and 39.5 cm for men to discriminate individuals with higher FINDRISC. Fully adjusted odds ratios for higher FINDRISC per 1-SD increase in NC in women and men were, respectively 1.89 (95% CI 1.53 - 2.33) and 2.86 (95% CI 1.91 - 4.29). NC is positively correlated to the body mass index, waist circumference, glycaemia, and FINDRISC scores in a population-based sample of adults. We identified the mean values of NC in higher and lower FINDRISC and established cutoff values for NC and higher FINDRISC.


Ethical considerations in providing an upper limb exoskeleton device for stroke patients.
The health care system needs to face new and advanced medical technologies that can improve the patients' quality of life by replacing lost or decreased functions. In stroke patients, the disabilities that follow cerebral lesions may impair the mandatory daily activities of an independent life. These activities are dependent mostly on the patient's upper limb function so that they can carry out most of the common activities associated with a normal life. Therefore, an upper limb exoskeleton device for stroke patients can contribute a real improvement of quality of their life. The ethical problems that need to be considered are linked to the correct adjustment of the upper limb skills in order to satisfy the patient's expectations, but within physiological limits. The debate regarding the medical devices dedicated to neurorehabilitation is focused on their ability to be beneficial to the patient's life, keeping away damages, injustice, and risks.


Cox2A/Cox2B subunit interaction in Polytomella sp. cytochrome c oxidase: role of the Cox2B subunit extension.
Subunit II of cytochrome c oxidase (Cox2) is usually encoded in the mitochondrial genome, synthesized in the organelle, inserted co-translationally into the inner mitochondrial membrane, and assembled into the respiratory complex. In chlorophycean algae however, the cox2 gene was split into the cox2a and cox2b genes, and in some algal species like Chlamydomonas reinhardtii and Polytomella sp. both fragmented genes migrated to the nucleus. The corresponding Cox2A and Cox2B subunits are imported into mitochondria forming a heterodimeric Cox2 subunit. When comparing the sequences of chlorophycean Cox2A and Cox2B proteins with orthodox Cox2 subunits, a C-terminal extension in Cox2A and an N-terminal extension in Cox2B were identified. It was proposed that these extensions favor the Cox2A/Cox2B interaction. In vitro studies carried out in this work suggest that the removal of the Cox2B extension only partially affects binding of Cox2B to Cox2A. We conclude that this extension is dispensable, but when present it weakly reinforces the Cox2A/Cox2B interaction.