A systematic review and meta-analysis on herpes zoster and the risk of cardiac and cerebrovascular events.
Patients who develop herpes zoster or herpes zoster ophthalmicus may be at risk for cerebrovascular and cardiac complications. We systematically reviewed the published literature to determine the association between herpes zoster and its subtypes with the occurrence of cerebrovascular and cardiac events. Systematic searches of PubMed (MEDLINE), SCOPUS (Embase) and Google Scholar were performed in December 2016. Eligible studies were cohort, case-control, and self-controlled case-series examining the association between herpes zoster or subtypes of herpes zoster with the occurrence of cerebrovascular and cardiac events including stroke, transient ischemic attack, coronary heart disease, and myocardial infarction. Data on the occurrence of the examined events were abstracted. Odds ratios and their accompanying confidence intervals were estimated using random and fixed effects models with statistical heterogeneity estimated with the I2 statistic. Twelve studies examining 7.9 million patients up to 28 years after the onset of herpes zoster met our pre-defined eligibility criteria. Random and fixed effects meta-analyses showed that herpes zoster, type unspecified, and herpes zoster ophthalmicus were associated with a significantly increased risk of cerebrovascular events, without any evidence of statistical heterogeneity. Our meta-analysis also found a significantly increased risk of cardiac events associated with herpes zoster, type unspecified. Our results are consistent with the accumulating body of evidence that herpes zoster and herpes zoster ophthalmicus are significantly associated with cerebrovascular and cardiovascular events.


[Cultivation of mammalian postimplantation embryos outside the body].
The possibility is considered to use in vitro cultivation of the embryos of laboratory rodents at the postimplantation developmental stages in experimental embryology and teratology. Different variants of the method are estimated and the optimal conditions of cultivation are described (nutrient medium, gaseous phase, depth of explants' immersion, rate of medium flow, etc). The causes are discussed which limit the duration of in vitro development and enhance the appearance of some defects. The results are given for application of the method when studying the mechanisms of teratogenic effect of chemical drugs.


[The treatment of esophageal achalasia in children by endoscopic pneumatic dilatation. A report on 4 cases].
Four patients underwent pneumatic endoscopic dilatation of achalasia at the La Fe Children's Hospital have been studied. Endoscopic pneumatic dilatation has been performed in only one session with four dilatation maneuvers. In the absence of complications, the patients were only hospitalized for twenty-four hours. The effectiveness of endoscopic pneumatic dilatation and the safety of this method, its ease of application and possibility of repetition make it a useful method in the treatment of achalasia in children.


Cutting edge: CD8+ recent thymic emigrants exhibit increased responses to low-affinity ligands and improved access to peripheral sites of inflammation.
To explore the TCR sensitivity of recent thymic emigrants (RTEs), we triggered T cells with altered peptide ligands (APLs). Upon peptide stimulation in vitro, RTEs exhibited increased TCR signal transduction, and following infection in vivo with APL-expressing bacteria, CD8 RTEs expanded to a greater extent in response to low-affinity Ags than did their mature T cell counterparts. RTEs skewed to short-lived effector cells in response to all APLs but also were characterized by diminished cytokine production. RTEs responding to infection expressed increased levels of VLA-4, with consequent improved entry into inflamed tissue and pathogen clearance. These positive outcomes were offset by the capacity of RTEs to elicit autoimmunity. Overall, salient features of CD8 RTE biology should inform strategies to improve neonatal vaccination and therapies for cancer and HIV, because RTEs make up a large proportion of the T cells in lymphodepleted environments.


Aqueous solvation from the water perspective.
The response of water re-solvating a charge-transfer dye (deprotonated Coumarin 343) after photoexcitation has been measured by means of transient THz spectroscopy. Two steps of increasing THz absorption are observed, a first ∼10 ps step on the time scale of Debye relaxation of bulk water and a much slower step on a 3.9 ns time scale, the latter of which reflecting heating of the bulk solution upon electronic relaxation of the dye molecules from the S1 back into the S0 state. As an additional reference experiment, the hydroxyl vibration of water has been excited directly by a short IR pulse, establishing that the THz signal measures an elevated temperature within ∼1 ps. This result shows that the first step upon dye excitation (10 ps) is not limited by the response time of the THz signal; it rather reflects the reorientation of water molecules in the solvation layer. The apparent discrepancy between the relatively slow reorientation time and the general notion that water is among the fastest solvents with a solvation time in the sub-picosecond regime is discussed. Furthermore, non-equilibrium molecular dynamics simulations have been performed, revealing a close-to-quantitative agreement with experiment, which allows one to disentangle the contribution of heating to the overall THz response from that of water orientation.


Improved oral bioavailability and therapeutic efficacy of erlotinib through molecular complexation with phospholipid.
The current study was aimed to prepare a molecular complex of erlotinib (ERL) with phospholipid (PC) for enhancement of solubility and thus bioavailability, therapeutic efficacy and reducing the toxicity of erlotinib. Phospholipid complex of drug was prepared by solvent evaporation method and characterized by differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FT-IR), proton and phosphorus nuclear magnetic resonance spectroscopy (1H NMR and 31P NMR), powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), which all explained the interactions of two components, validating the complexation phenomenon. In silico study also supported the phase change and molecular interactions for the establishment of ERL-PC. Spherical shaped nanostructures with 183.37±28.61nm size, -19.52±6.94mV potential and 28.59±2.66% loading efficiency were formed following dispersion of ERL-PC in aqueous media. In vitro release study revealed the higher release of ERL-PC due to amorphization and solubilization of drug. Caco-2 cell uptake resulted in ∼2 fold higher uptake of ERL-PC than free drug. In vitro cell culture studies were performed using human pancreatic adenocarcinoma cell lines, which demonstrated the higher cytotoxicity and apoptosis in case of ERL-PC. In vivo pharmacokinetics also supported the in vitro observations and showed ∼1.7 fold higher bioavailability with ERL-PC than ERL. Finally, in vivo efficacy and toxicity studies explained the superiority of ERL-PC over the free drug. Based on the results, phospholipid complex appears to be a promising tool to enhance bioavailability, efficacy, cytotoxicity and safety of erlotinib.


Clinical experience of pelvic radiotherapy or chemoradiotherapy for postoperative uterine cervical cancer using intensity-modulated radiation therapy.
The purpose of this study was to reveal treatment outcomes and toxicity after pelvic intensity-modulated radiotherapy (IMRT) for postoperative uterine cervical cancer of Japanese patients. Consecutive patients who were treated with pelvic IMRT for postoperative cervical cancer in our institute were retrospectively analyzed. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier estimator, and log-rank tests were used to compare differences. From the database, 62 patients were identified. The pathology was squamous cell carcinoma in 44 patients and other pathology in 18 patients. Of the 62 patients, 35 had high-risk prognostic factors and 27 patients had intermediate-risk prognostic factors. The prescribed radiation doses were 50 Gy in 25 fractions for 58 patients and 50.4 Gy in 28 fractions for 4 patients. One patient received a vaginal cuff boost. Chemotherapy was administered in 36 patients. During the median follow-up period of 50.9 months, there was no locoregional failure. Six patients in the high-risk group relapsed, but none of the patients in the intermediate-risk group relapsed (P = 0.02). The 3-year OS and RFS rates were 98.2% and 90.9%, respectively. Significant factors related to RFS were squamous cell carcinoma pathology (P = 0.02), pathological T stage (P = 0.04), surgical margin status (P < 0.01) and multiple lymph nodes metastases (P < 0.01). Grade 3 or more toxicity occurred in 6 patients. Four patients had obstruction of the intestine, and 2 patients had stenosis of the urinary tract. In clinical practice, the use of pelvic IMRT for postoperative cervical cancer of Japanese patients showed a low rate of toxicity without decreasing the efficacy.


Digital Quality Improvement Approach Reduces the Need for Rescue Antiemetics in High-Risk Patients: A Comparative Effectiveness Study Using Interrupted Time Series and Propensity Score Matching Analysis.
Affecting nearly 30% of all surgical patients, postoperative nausea and vomiting (PONV) can lead to patient dissatisfaction, prolonged recovery times, and unanticipated hospital admissions. There are well-established, evidence-based guidelines for the prevention of PONV; yet physicians inconsistently adhere to them. We hypothesized that an electronic medical record-based clinical decision support (CDS) approach that incorporates a new PONV pathway, education initiative, and personalized feedback reporting system can decrease the incidence of PONV. Two years of data, from February 17, 2015 to February 16, 2016, was acquired from our customized University of California Los Angeles Anesthesiology perioperative data warehouse. We queried the entire subpopulation of surgical cases that received general anesthesia with volatile anesthetics, were ≥12 years of age, and spent time recovering in any of the postanesthesia care units (PACUs). We then defined PONV as the administration of an antiemetic medication during the aforementioned PACU recovery. Our CDS system incorporated additional PONV-specific questions to the preoperative evaluation form, creation of a real-time intraoperative pathway compliance indicator, initiation of preoperative PONV risk alerts, and individualized emailed reports sent weekly to clinical providers. The association between the intervention and PONV was assessed by comparing the slopes from the incidence of PONV pre/postintervention as well as comparing observed incidences in the postintervention period to what we expected if the preintervention slope would have continued using interrupted time series analysis regression models after matching the groups on PONV-specific risk factors. After executing the PONV risk-balancing algorithm, the final cohort contained 36,796 cases, down from the 40,831 that met inclusion criteria. The incidence of PONV before the intervention was estimated to be 19.1% (95% confidence interval [CI], 17.9%-20.2%) the week before the intervention. Directly after implementation of the CDS, the total incidence decreased to 16.9% (95% CI, 15.2%-18.5%; P = .007). Within the high-risk population, the decrease in the incidence of PONV went from 29.3% (95% CI, 27.6%-31.1%) to 23.5% (95% CI, 20.5%-26.5%; P < .001). There was no significant difference in the PONV incidence slopes over the entire pre/postintervention periods in the high- or low-risk groups, despite an abrupt decline in the PONV incidence for high-risk patients within the first month of the CDS implementation. We demonstrate an approach to reduce PONV using individualized emails and anesthesia-specific CDS tools integrated directly into a commercial electronic medical record. We found an associated decrease in the PACU administration of rescue antiemetics for our high-risk patient population.


Leptin signaling in breast cancer: an overview.
The adipocyte-derived peptide leptin acts through binding to specific membrane receptors, of which six isoforms (obRa-f) have been identified up to now. Binding of leptin to its receptor induces activation of different signaling pathways, including the JAK/STAT, MAPK, IRS1, and SOCS3 signaling pathways. Since the circulating levels of leptin are elevated in obese individuals, and excess body weight has been shown to increase breast cancer risk in postmenopausal women, several studies addressed the role of leptin in breast cancer. Expression of leptin and its receptors has been demonstrated to occur in breast cancer cell lines and in human primary breast carcinoma. Leptin is able to induce the growth of breast cancer cells through activation of the Jak/STAT3, ERK1/2, and/or PI3K pathways, and can mediate angiogenesis by inducing the expression of vascular endothelial growth factor (VEGF). In addition, leptin induces transactivation of ErbB-2, and interacts in triple negative breast cancer cells with insulin like growth factor-1 (IGF-1) to transactivate the epidermal growth factor receptor (EGFR), thus promoting invasion and migration. Leptin can also affect the growth of estrogen receptor (ER)-positive breast cancer cells, by stimulating aromatase expression and thereby increasing estrogen levels through the aromatization of androgens, and by inducing MAPK-dependent activation of ER. Taken together, these findings suggest that the leptin system might play an important role in breast cancer pathogenesis and progression, and that it might represent a novel target for therapeutic intervention in breast cancer.


The Challenges of Leadership.
Perhaps in no other period in recent times have the challenges leaders face been so profound. In these times of uncertainty and turbulence, we look to leaders who create a sense of purpose, who generate feelings of trust and optimism, and who tap the passion, talent, and efforts of those so essential to the success of the organization and of the people it serves. Our research suggests that becoming the leader whom people look to and admire requires an active commitment to responding to 5 essential leadership challenges. These are (1) creating a sense of purpose, (2) devising means for aligning the actions of the followers with that sense of purpose, (3) establishing a context that enables others to behave in a way that is consistent with the vision and values of the organization, (4) ensuring that the work that is done provides meaning to those engaging in the work activities, and (5) adding to the sum of everyone's knowledge through learning through reflective actions. In this article, we describe these challenges and offer suggestions that you can take to become a more effective and respected leader.


Potential role of platelets in the pathogenesis of tumor metastasis.
Platelet activity may be involved in tumor metastasis. The tumor cells, after detachment from the primary site, adhere to vascular endothelium at distant sites and proliferate. Platelets form aggregates with tumor cells in circulation, facilitating their adhesion to the vascular endothelium. Formation of platelet-tumor cell aggregates and their sequestration in various end-organs may result in thrombocytopenia. Certain tumor cell lines directly stimulate platelet activity, some by releasing platelet-aggregating material, a urea-extractable membrane component, others by release of cathepsin, and still others by undefined mechanisms. The direct effect of platelets on tumor cells may be of pathogenic significance. For example, platelet-derived factors stimulate growth of some tumors, whereas others increase vascular permeability and thus facilitate migration of tumor cells across the vessel wall. Lack of these platelet factors, as in thrombocytopenic animals, may indeed inhibit tumor metastasis. Arachidonic acid metabolism in platelets and the vessel walls may contribute to metastatic process. In particular, thromboxane A2 and prostacyclin generation capabilities appear to be important in modulating platelet-tumor cell deposition and growth. To alter the metastatic process, several preliminary trials of platelet-inhibitory agents have been performed. However, the results of these trials have been equivocal, perhaps related to nonspecific effects of these agents on arachidonic acid metabolism. Studies directed at specific pathways of platelet-vessel wall interaction on some tumors appear promising. These newer agents may be of therapeutic value in man.


Novel MAB phases and insights into their exfoliation into 2D MBenes.
Considering the recent breakthroughs in the synthesis of novel two-dimensional (2D) materials from layered bulk structures, ternary layered transition metal borides, known as MAB phases, have come under scrutiny as a means of obtaining novel 2D transition metal borides, the so-called MBenes. Here, based on a set of phonon calculations, we show the dynamic stability of many Al-containing MAB phases, MAlB (M = Ti, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Tc), M2AlB2 (Sc, Ti, Zr, Hf, V, Cr, Mo, W, Mn, Tc, Fe, Rh, Ni), M3Al2B2 (M = Sc, T, Zr, Hf, Cr, Mn, Tc, Fe, Ru, Ni), M3AlB4 (M = Sc, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Fe), and M4AlB6 (M = Sc, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo). By comparing the formation energies of these MAB phases with those of their available competing binary M-B and M-Al, and ternary M-Al-B phases, we find that some of the Sc-, Ti-, V-, Cr-, Mo-, W-, Mn-, Tc-, and Fe-based MAB phases could be favorably synthesized under appropriate experimental conditions. In addition, by examining the strengths of various bonds in MAB phases via crystal orbital Hamilton population and spring constant calculations, we find that the B-B and then M-B bonds are stiffer than the M-Al and Al-B bonds. The different strengths between these bonds imply the etching possibility of Al atoms from MAB phases, consequently forming various 2D MB, M2B3, and M3B4 MBenes. Furthermore, we employ the nudged elastic band method to investigate the possibility of the structural phase transformation of the 2D MB MBenes into graphene-like boron sheets sandwiched between transition metals and find that the energy barrier of the transformation is less than 0.4 eV per atom.


Determination of an adequate perfusion pressure for continuous dual vessel hypothermic machine perfusion of the rat liver.
Hypothermic machine perfusion (HMP) provides better protection against ischemic damage of the kidney compared to cold-storage. The required perfusion pressures needed for optimal HMP of the liver are, however, unknown. Rat livers were preserved in University of Wisconsin organ preservation solution enriched with acridine orange (AO) to stain viable cells and propidium iodide (PI) to detect dead cells. Perfusion pressures of 12.5%, 25% or 50% of physiologic perfusion pressures were compared. Intravital fluorescence microscopy was used to assess liver perfusion by measuring the percentage of AO staining. After 1-h, the perfusion pressure of 12.5% revealed 72% +/- 3% perfusion of mainly the acinary zones one and two. The perfusion pressure of 25% and 50% showed complete perfusion. Furthermore, 12.5% showed 14.7 +/- 3.6, 25% showed 3.7 +/- 0.9, and 50% showed 11.2 +/- 1.4 PI positive cells. One hour was followed by another series of experiments comprising 24-h preservation. In comparison with 24-h cold-storage, HMP at 25% showed less PI positive cells and HMP at 50% showed more PI positive cells. In summary, perfusion at 25% showed complete perfusion, demonstrated by AO staining, with minimal cellular injury, shown with PI. This study indicates that fine-tuning of the perfusion pressure is crucial to balance (in)complete perfusion and endothelial injury.


STAR particles for enhanced topical drug and vaccine delivery.
Drug delivery to the skin is highly constrained by the stratum corneum barrier layer1. Here, we developed star-shaped particles, termed STAR particles, to dramatically increase skin permeability. STAR particles are millimeter-scale particles made of aluminum oxide or stainless steel with micron-scale projections designed to create microscopic pores across the stratum corneum. After gentle topical application for 10 s to porcine skin ex vivo, delivery of dermatological drugs and macromolecules, including those that cannot be given topically, was increased by 1 to 2 orders of magnitude. In mice treated with topical 5-fluorouracil, use of STAR particles increased the efficacy of the drug in suppressing the growth of subcutaneous melanoma tumors and prolonging survival. Moreover, topical delivery of tetanus toxoid vaccine to mice using STAR particles generated immune responses that were at least as strong as delivery of the vaccine by intramuscular injection, albeit at a higher dose for topical than intramuscular vaccine administration. STAR particles were well tolerated and effective at creating micropores when applied to the skin of human participants. Use of STAR particles provides a simple, low-cost and well-tolerated method for increasing drug and vaccine delivery to the skin and could widen the range of compounds that can be topically administered.


HIV sexual risk behavior by men who use the Internet to seek sex with men: results of the Men's INTernet Sex Study-II (MINTS-II).
This study sought to identify the magnitude of HIV risk in a diverse sample of Men who use the Internet to seek Sex with Men (MISM), and test if specific subpopulations are at sufficiently increased risk to warrant tailored interventions. A sample of 2,716 American MISM, stratified by race/ethnicity, completed an Internet survey of online and offline sex seeking behavior during the last 3 months. Across most demographics, a minority of MISM reported unprotected anal intercourse with male partners (UAIMP). Across all demographics, risk of UAIMP substantially increased with partners met online. Other predictors of increased online partner risk include being 30-39 years old, having children, not living in the Northeast, and low income. HIV-positive men and African Americans reported increased online and offline partner risk. To address higher risk of UAIMP, online HIV interventions should prioritize the needs of MISM, especially HIV-positive men, with content focused on online-mediated liaisons.


The signal functions of early infant crying.
In this article I evaluate recent attempts to illuminate the human infant cry from an evolutionary perspective. Infants are born into an uncertain parenting environment, which can range from indulgent care of offspring to infanticide. Infant cries are in large part adaptations that maintain proximity to and elicit care from caregivers. Although there is not strong evidence for acoustically distinct cry types, infant cries may function as a graded signal. During pain-induced autonomic nervous system arousal, for example, neural input to the vocal cords increases cry pitch. Caregivers may use this acoustic information, together with other cues, to guide caregiving behavior. Serious pathology, on the other hand, results in chronically and severely abnormal cry acoustics. Such abnormal crying may be a proximate cause of adaptive infant maltreatment, in circumstances in which parents cut their losses and reduce or withdraw investment from infants with low survival chances. An increase in the amount of crying during the first few months of life is a human universal, and excessive crying, or colic, represents the upper end of this normal increase. Potential signal functions of excessive crying include manipulation of parents to acquire additional resources, honest signaling of need, and honest signaling of vigor. Current evidence does not strongly support any one of these hypotheses, but the evidence is most consistent with the hypothesis that excessive early infant crying is a signal of vigor that evolved to reduce the risk of a reduction or withdrawal of parental care.


Ecology and diversity in upper respiratory tract microbial population structures from a cross-sectional community swabbing study.
Respiratory tract infections (RTIs) are responsible for over 2.8 million deaths per year worldwide with pathobiont carriage a required precursor to infection. We sought to determine carriage epidemiology for both bacterial and viral respiratory pathogens as part of a large population-based cross-sectional carriage study. Nose self-swab samples were collected in two separate time-points, May to August 2012 (late spring/summer) and February to April 2013 (winter/early spring). The presence of six bacterial species: S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, P. aeruginosa and N. meningitidis in addition to respiratory syncytial virus, influenza viruses A and B, rhinovirus/enterovirus, coronavirus, parainfluenza viruses 1-3 and adenovirus was determined using culture and PCR methods.Results/Key findings. Carriage was shown to vary with age, recent RTI and the presence of other species. Spatial structures of microbial communities were more disordered in the 0-4 age group and those with recent RTI. Species frequency distributions were flatter than random expectation in young individuals (X2=20.42, P=0.002), indicating spatial clumping of species consistent with facilitative relationships. Deviations from a neutral model of ecological niches were observed in summer samples and from older individuals but not in the winter or younger individuals (0-4 years), suggesting the presence of seasonal and age-dependent niche processes in respiratory community assembly. The application of epidemiological methods and ecological theory to respiratory tract samples has yielded novel insights into the factors that drive microbial community composition.


Complete absence of the third component of complement in man.
A 4-yr-old female patient who has recurrent infections with encapsulated bacteria and gramnegative organisms was found to have a complete absence of total hemolytic complement and C3. Total hemolytic complement was reconstituted by the addition of functionally pure C3. With the exception of a moderately reduced homolytic C4, all other C components, measured homolytically and by radial immunodiffusion, were present in normal amounts. By Ouchterlong analysis, the patient's serum contained C3b inactivator and properdin but no antigenic C3. Activation of the alternate pathway was examined by purified cobra venom factor (CVF) and inulin. Neither of these substances led to activation of properdin factor B to B. On addition of partially purified Cordis C3, in four out of four instances and with different preparations of Cordis C3, activation of factor B to B occurred in the inulin-serum-C3 mixture. In contrast, activation of factor B to B occurred only once out of four times with CVF-serum-C3 mixtures. Immune adherence was found to be normal in the patient's serum and could be removed by anti-C4 antiserum of hydrazine treatment. A marked opsonic defect was present against Escherichia coli. Serum bactericidal activity against a rough strain of E. coli was also defective. The ability to mobilize an infalmmatory response was examined by Rebuck skin window technique. A delay in neutrophil migration occurred until the 6th h. In vitro lymphocyte transformation and serum immunoglobulins were normal. The proportion of peripheral blood T cells forming spontaneous sheep erythrocyte rosettes and the percentage of B cells forming EAC rosettes by the C3 receptor were normal. The significance of the absence of C3 in our patient is emphasized by the increased number of infections with encapsulated bacteria and the decreased functional biological activities of the C system, important in host defense mechanism(s).


The Intricate Dance of Infections and Autoimmunity: An Interesting Paradox.
Besides genetic susceptibility, infections due to viruses, bacteria and protozoa have been implicated in the development of autoimmune diseases (AD). AD can be triggered in a genetically susceptible individual by infections that disrupt immunological tolerance towards self-antigens. Pathogens can initiate autoimmunity by way of molecular mimicry, bystander activation, epitope spreading or persistent infection with polyclonal activation. This review covers two main topics: (i) the mechanisms by which an infectious agent can trigger or worsen autoimmunity; and (ii) the correlation between specific infectious agents and AD in humans with special emphasis on multisystem inflammatory syndrome in children (MIS-C).


In-Vitro Growth Kinetics of Mesenchymal Stem Cells in Cytotoxicity Tests Using Low-Diluted Viscum Album.
The use of mesenchymal stem cells (MSC) in cytotoxicity tests is an in-vitro alternative model for predicting initial doses. Homeopathic medicines may stimulate the immune system to combat a pathology effectively and have been used for over two centuries. Viscum album (VA) extracts are widely used in the treatment of cancer, due to their immunomodulatory, cytotoxic and pro-apoptotic properties. This study aimed to evaluate the in-vitro growth kinetics of canine MSC in relation to cytotoxicity, cell differentiation and expression of pluripotentiality markers, using a VA preparation at the D1D2 (1×10-1, 1×10-2 potency (VAD1D2). MSC were obtained from adipose tissue sampled from a healthy dog that was undergoing an elective veterinary procedure and with its owner's permission. The experiments were performed in three groups: MSC treated with VAD1D2 or diluent or untreated (control). The cytotoxicity was evaluated by MTT assay. The differentiation was induced in three lineages, and apoptotic cell labeling was performed by an Annexin-V test. At the concentration of 10 μL/mL of VA, the number of cells after in-vitro culture was maintained when compared with the control (untreated) group. A significant and gradual decrease in cell viability was recorded as VA concentrations increased. The apoptosis analysis showed that VA at 20 μL/mL presented absolute percentages of initial apoptosis twice as high as at 10 μL/mL, which was similar to the control (untreated group). The results suggest that the use of efficient methods to assess the in-vitro cytotoxicity of VA-based homeopathic medicines using MSC lineages may predict the potential action at different concentrations. These findings demonstrated that VAD1D2 interferes with canine MSC growth kinetics.


[Histiocytic necrotizing lymphadenitis: report of 3 cases].
Histiocytic necrotizing lymphadenitis (also known as Kikuchi-Fujimoto's disease) is an uncommon, benign and self-limiting lymph disease. We report three patients aged 14, 22 and 50 years, who presented with fever and cervical lymphadenopathy, accompanied by skin lesions and joint pain in two of the three cases. One of the patient's sister suffered from histiocytic necrotizing lymphadenitis. Laboratory abnormalities varied and findings included leucopenia, relative neutrophilia, elevated C reactive protein, erythrocyte sedimentation rate and ferritin. Basic laboratory screening tests were performed on all patients to rule out autoimmune and infectious diseases. Lymph node biopsy and subsequent pathological examination were essential to establish the diagnosis. All patients received antibiotics at some point of their hospital stay. Two patients required glucocorticoid treatment, while the remaining case experienced a spontaneous recovery. Its pathogenesis is still unknown, but clinical and histopathological studies suggest a connection with autoimmune diseases. There is no established treatment, but apparently the disease responds to the administration of glucocorticoids.


Local Electron Environment Regulation of Spinel CoMn2O4 Induced Effective Reactant Adsorption and Transformation of Lattice Oxygen for Toluene Oxidation.
In contrast to numerous studies on oxygen species, the interaction of volatile organic compounds (VOCs) with oxides is also critical to the catalytic reaction but has hardly been considered. Herein, we develop a highly efficient Pt atom doped spinel CoMn2O4 (Pt-CoMn) for oxidation of toluene at low temperature, and the toluene conversion rate increased by 18.3 times (129.7 versus 7.1 × 10-11 mol/(m2·s)) at 160 °C compared to that of CoMn2O4. Detailed characterizations and density functional theory calculations reveal that the local electron environment of the Co sites is changed after Pt doping, and the formed electron-deficient Co sites in turn strengthen the interaction with toluene. Adsorbed toluene will react with lattice oxygen in Pt-CoMn and CoMn catalysts and convert into benzoate intermediates, and the consumption rate of benzoate is closely related to the activation of gaseous oxygen. Significantly, the abundant bulk defects of Pt-CoMn help to open the reaction channel in the CoMn spinel, which acts as an oxygen pump to promote the transformation of bulk lattice oxygen into surface lattice oxygen at lower temperatures, thus accelerating the conversion rate of benzoate intermediates into CO2 and enhancing low-temperature combustion of toluene. Pt-CoMn developed here emphasizes the regulation of VOCs adsorption strength and lattice oxygen transformation processes on CoMn2O4 by adjusting the local electron environment, which will provide new guidance for the design of efficient oxide catalysts for catalytic oxidation.


Serial beta-hCG measurements in the early detection of ectopic pregnancy.
We investigated the sensitivity and specificity of serial serum hCG assays to diagnose early ectopic pregnancy in 50 asymptomatic women at risk. The initial two hCG values obtained at 2-5-day intervals were used to calculate doubling time and percentage increase. Twenty-five women had a viable intrauterine pregnancy, 14 an ectopic gestation, ten a spontaneous abortion, and one a molar pregnancy. A normal percentage increase and/or doubling time was observed in 64% of women who eventually proved to have an ectopic pregnancy. Ultimately, 85% of our patients demonstrated abnormal values when subsequent hCG pairs were analyzed. The sensitivity of these tests to diagnose asymptomatic ectopic pregnancy was 36%, with a specificity of 63-71%. We conclude that a normal rise in hCG production does not reliably differentiate an ectopic from an intrauterine pregnancy in the asymptomatic patient.


Secondary amine selective Petasis (SASP) bioconjugation.
Selective modification of proteins enables synthesis of antibody-drug conjugates, cellular drug delivery and construction of new materials. Many groups have developed methods for selective N-terminal modification without affecting the side chain of lysine by judicious pH control. This is due to lower basicity of the N-terminus relative to lysine side chains. But none of the methods are capable of selective modification of secondary amines or N-terminal proline, which has similar basicity as lysine. Here, we report a secondary amine selective Petasis (SASP) reaction for selective bioconjugation at N-terminal proline. We exploited the ability of secondary amines to form highly electrophilic iminium ions with aldehydes, which rapidly reacted with nucleophilic organoboronates, resulting in robust labeling of N-terminal proline under biocompatible conditions. This is the first time the Petasis reaction has been utilized for selective modification of secondary amines on completely unprotected peptides and proteins under physiological conditions. Peptide screening results showed that the reaction is highly selective for N-terminal proline. There are no other chemical methods reported in literature that are selective for N-terminal proline in both peptides and proteins. This is a multicomponent reaction leading to the synthesis of doubly functionalized bioconjugates in one step that can be difficult to achieve using other methods. The key advantage of the SASP reaction includes its high chemoselective and stereoselective (>99% de) nature, and it affords dual labeled proteins in one pot. The broad utility of this bioconjugation is highlighted for a variety of peptides and proteins, including aldolase and creatine kinase.


The morphogenesis of the ventricular flow pathways in man.
This work which is based on the study of eight human embryos of 4,5 to 13,6 mm from the Madrid collection, and also on six plastic reconstructions made by the BORN method, and on experiments on chick embryos (ligature of the left vitelline vein in embryos, 3 days of incubation) enables us to reach the following conclusions: no true rotatiorial movements take place during normogensis. Only ventromedial rotation of the right ventricle is observed in stages 12 to 14. This rotation will place the right ventricle, and therefore the vestibulum pulmonalis in front of the aortic infundibulum. We consider that the initiation of cardiac septation is to a great extent due to hemodynamic. causes. During normogenesis in all cases, from the earliest stages of development the presumptive pulmonary outflow tract is always anterior and to the right of the presumptive aortic tract. We do not agree with the statement of GOOR and EDWARDS and VAN PRAAGH R. and VAN PRAAGH S. (1965), that in some stages the presumptive coni of the aorta and pulmonalis are arranged inversely to the way in which they will arranged later.


Who's caring for whom? Differing perspectives between seriously ill patients and their family caregivers.
Although clinicians and researchers often rely on family members 'reports of a wide range of dying patients' symptoms and care preferences, available data indicate divergences between the two. We used a national sample to analyze patient-caregiver pairs to explore areas of concordance and nonconcordance about physical symptoms, communication with physicians, caregiving needs, and future fears. We also assessed whether identifiable patient or caregiver characteristics were associated with nonconcordance. Our data were from a national, random sample of 988 terminally ill patients, of whom 893 had caregivers who were also interviewed. Frequencies and types of nonconcordance were computed for patient-caregiver pairs. Bivariate associations between patient and caregiver reports on each item were tested. Logistic and conditional logistic regression analyses assessed multiple predictors of nonconcordance for each item. Primary diagnoses included cancer (51.1 percent), heart disease (17. 7 percent), chronic obstructive pulmonary disease (10. 7 percent), and other diseases (20.5 percent). The proportion of concordant reports among pairs of patients and caregivers ranged from 53 percent to 66 percent. Among pairs showing nonconcordant responses, caregivers reported higher levels of pain and disability than patients, lower caregiving needs, and different fears about the future. Few demographic or clinical predictors were associated with nonconcordance. Concordance between patients 'and their caregivers' responses ranged widely, and there were important areas of nonconcordant responses. When responses differed, patients were more likely to express concern about domains that might impose on caregivers, while caregivers were more likely to express concern about patients 'physical suffering. Consistent sociodemographic or clinical predictors of nonconcordant responses were not found. These data suggest important ways that patient and caregiver reports of the same experience vary.


Training induced alterations of visual evoked potentials are not related to body temperature.
The purpose of this study was to investigate the effect of mild chronic exercise on visual evoked potentials (VEPs). Twenty male Wistar rats were randomly divided into two groups: Control (C) and Exercise (E) groups. Exercise was performed on a motor-driven treadmill for 8 weeks. After 5 min of exercise, plasma lactic acid levels were determined. At the end of the experimental period, VEPs were recorded from E group twice: Five min (E-5 min) and 24 h (E-24 h) after the last bout of exercise. During visual evoked potential (VEP) recordings body temperature of the animals was kept constant to eliminate the effect of temperature changes. No difference was found between the lactic acid levels of two groups. The mean latencies of VEPs from E-5 min were shortened compared with the control group. The mean latencies of VEP components in E-24 h were observed to have returned to the control levels. Peak to peak amplitudes of VEPs were found to be unaltered among all measurements. We concluded that immediately after exercise, VEPs latencies were shortened independently from body temperature via unknown mechanisms. The latencies of VEPs were returned to control values after 24 h.


Artificial spatiotemporal touch inputs reveal complementary decoding in neocortical neurons.
Investigations of the mechanisms of touch perception and decoding has been hampered by difficulties in achieving invariant patterns of skin sensor activation. To obtain reproducible spatiotemporal patterns of activation of sensory afferents, we used an artificial fingertip equipped with an array of neuromorphic sensors. The artificial fingertip was used to transduce real-world haptic stimuli into spatiotemporal patterns of spikes. These spike patterns were delivered to the skin afferents of the second digit of rats via an array of stimulation electrodes. Combined with low-noise intra- and extracellular recordings from neocortical neurons in vivo, this approach provided a previously inaccessible high resolution analysis of the representation of tactile information in the neocortical neuronal circuitry. The results indicate high information content in individual neurons and reveal multiple novel neuronal tactile coding features such as heterogeneous and complementary spatiotemporal input selectivity also between neighboring neurons. Such neuronal heterogeneity and complementariness can potentially support a very high decoding capacity in a limited population of neurons. Our results also indicate a potential neuroprosthetic approach to communicate with the brain at a very high resolution and provide a potential novel solution for evaluating the degree or state of neurological disease in animal models.


Dietary folate intake in combination with MTHFR C677T genotype and promoter methylation of tumor suppressor and DNA repair genes in sporadic colorectal adenomas.
Methylation of the promoter region of tumor suppressor genes is increasingly recognized to play a role in cancer development through silencing of gene transcription. We examined the associations between dietary folate intake, MTHFR C677T genotype, and promoter methylation of six tumor suppressor and DNA repair genes. Patients with colorectal adenoma (n = 149) and controls (n = 286) with folate intake in the upper or lower tertile with the CC or TT genotype were selected from a case-control study. Methylation-specific PCRs were conducted on colorectal adenoma specimens. The percentages of promoter methylation ranged from 15.7% to 64.2%. In case-case comparisons, folate was inversely associated with promoter methylation, especially among TT homozygotes. Case-control comparisons suggested that folate was not associated with the occurrence of adenomas with promoter methylation, and increased the risk of unmethylated adenomas, especially in TT homozygotes. The interactions between folate and MTHFR genotype were most pronounced for O(6)-MGMT: compared with CC homozygotes with low folate intake, the adjusted odds ratios (95% confidence interval) of having a methylated O(6)-MGMT promoter were 3.39 (0.82-13.93) for TT homozygotes with low folate intake and 0.37 (0.11-1.29) for TT homozygotes with high folate intake (P interaction = 0.02); the odds ratios for the occurrence of adenomas without methylation were 0.57 (0.16-2.11) for TT homozygotes with low folate intake and 3.37 (1.17-9.68) for TT homozygotes with high folate intake (P interaction = 0.03). In conclusion, folate intake seems to be inversely associated with promoter methylation in colorectal adenomas in case-case comparisons, and was positively associated with the occurrence of adenomas without promoter methylation in case-control comparisons, especially for TT homozygotes.


Efficacy of Various Facial Protective Equipment for Infection Control in a Healthcare Setting.
The coronavirus 2019 (COVID-19) pandemic has reinforced the importance of facial protection against droplet transmission of diseases. Healthcare workers wear personal protection equipment (PPE), including face shields and masks. Plastic face shields may have advantages over regular medical masks. Although many designs of face shields exist, there is a paucity of evidence regarding the efficacy of shield designs against droplet transmissions. There is even less published evidence comparing various face shields. Due to the urgency of the pandemic and the health and safety of healthcare workers, we aimed to study the efficacy of various face shields against droplet transmission. We simulated droplet transmission via coughing using a heavy-duty chemical spray bottle filled with fluorescein. A standard-adult sized mannequin head was used. The mannequin head wore various face shields and was positioned to face the spray bottle at either a 0°, 45°, or 90° angle. The spray bottle was positioned at and sprayed from 30 centimeters (cm), 60 cm, or 90 cm away from the head. These steps were repeated for all face shields used. Control was a mannequin that wore no PPE. A basic mask was also tested. We collected data for particle count, total area of particle distribution, average particle size, and percentage area covered by particles. We analyzed percent covered by particles using a repeated measures mixed-model regression with Tukey-Kramer pairwise comparison. We used least square means to estimate the percentage area covered by particles. Wearing PPE regardless of the design reduced particle transmission to the mannequin compared to the control. The LCG mask had the lowest square means of 0.06 of all face-shield designs analyzed. Tukey-Kramer pairwise comparison showed that all PPEs had a decrease in particle contamination compared to the control. LCG shield was found to have the least contamination compared to all other masks (P < 0.05). Results suggest the importance of wearing a protective covering against droplet transmission. The LCG shield was found to decrease facial contamination by droplets the most of any tested protective equipment.


Biocatalysis in the Recycling Landscape for Synthetic Polymers and Plastics towards Circular Textiles.
Although recovery of fibers from used textiles with retained material quality is desired, separation of individual components from polymer blends used in today's complex textile materials is currently not available at viable scale. Biotechnology could provide a solution to this pressing problem by enabling selective depolymerization of recyclable fibers of natural and synthetic origin, to isolate constituents or even recover monomers. We compiled experimental data for biocatalytic polymer degradation with a focus on synthetic polymers with hydrolysable links and calculated conversion rates to explore this path The analysis emphasizes that we urgently need major research efforts: beyond cellulose-based fibers, biotechnological-assisted depolymerization of plastics so far only works for polyethylene terephthalate, with degradation of a few other relevant synthetic polymer chains being reported. In contrast, by analyzing market data and emerging trends for synthetic fibers in the textile industry, in combination with numbers from used garment collection and sorting plants, it was shown that the use of difficult-to-recycle blended materials is rapidly growing. If the lack of recycling technology and production trend for fiber blends remains, a volume of more than 3400 Mt of waste will have been accumulated by 2030. This work highlights the urgent need to transform the textile industry from a biocatalytic perspective.


Cadmium accumulation in sunflower plants influenced by arbuscular mycorrhiza.
In order to investigate the cadmium (Cd) accumulation patterns and possible alleviation of Cd stress by mycorrhization, sunflower plants (Helianthus annuus L.) were grown in the presence or absence of Cd (20 micromol L(-1)) and inoculated or not inoculated with the arbuscular mycorrhizal fungus (AMF) Glomus intraradices. No visual symptoms of Cd phytotoxicity were observed; nevertheless, in non-mycorrhizal plants the presence of Cd decreased plant growth. The addition of Cd had no significant effect on either mycorrhizal colonization or the amount of extra-radical mycelia that was produced by the AMF. Cd accumulated mainly in roots; only 22% of the total Cd absorbed was translocated to the shoots, where it accumulated to an average of 228 mg Cd kg(-1). Although the shoot-to-root ratio of Cd was similar in both the AMF inoculated and non-inoculated plants, the total absorbed Cd was 23% higher in mycorrhizal plants. Cd concentration in AMF extra-radical mycelium was 728 microg g(-1) dry weight. Despite the greater absorption of Cd, mycorrhizal plants showed higher photosynthetic pigment concentrations and shoot P contents. Cd also influenced mineral nutrition, leading to decreased Ca and Cu shoot concentrations; N, Fe and Cu shoot contents; and increased S and K shoot concentrations. Cd induced guaiacol peroxidase activity in roots in both mycorrhizal and non-mycorrhizal plants, but this increase was much more accentuated in non-mycorrhizal roots. In conclusion, sunflower plants associated with G. intraradices were less sensitive to Cd stress than non-mycorrhizal plants. Mycorrhizal sunflowers showed enhanced Cd accumulation and some tolerance to excessive Cd concentrations in plant tissues.


Refinement of the Well-being in Pregnancy (WiP) questionnaire: cognitive interviews with women and healthcare professionals and a validation survey.
Measuring positive and negative aspects of well-being during pregnancy and childbirth is important for both healthy women and women who are living with long-term health conditions (LTCs). This study aimed to further refine the Well-being in Pregnancy (WiP) questionnaire and to incorporate LTC specific items where appropriate. A multi-method study. Cognitive interviews with pregnant or postpartum women (n = 11) and consultations with healthcare professionals (n = 11) and public representatives (n = 4) were conducted to explore the acceptability of existing WiP items and content. Items were refined and subsequently administered on an online survey (n = 768). Item reduction steps and exploratory factor analysis were performed on survey data. Convergent validity was examined using Pearson correlation coefficients to compare relationships with other included validated assessments. Following amendments to three items, the addition of eight core WiP items and five LTC specific items, a total of 25 items were considered relevant and appropriate for use with pregnant women. Analysis of survey data reduced the questionnaire to 12 items measuring three core WiP scales; 1) Concerns over support after birth, 2) Positive pregnancy and, 3) Confidence about motherhood, and a five item standalone LTC specific scale. All scales demonstrated good validity and internal reliability. Scores for the three core scales moderately correlated with established well-being measures indicating that they were measuring similar, yet distinct concepts. Analyses confirmed good psychometric properties of the refined WiP questionnaire. The use of pregnancy specific well-being measures, such as the WiP, provide a route into asking women in more detail about how their care may be tailored to support them and also facilitates positive conversations with women about how care and experience of pregnancy and childbirth may be enhanced further.


Effects of natural environment on reproductive histo-morphometric dynamics of female dromedary camel.
Camel shows a seasonal breeding pattern with enhanced reproductive activity during the period of low climatic temperature, high rainfall and better food conditions. Therefore, the study was conducted to explore the underlying seasonal effects on histological dimensions of reproductive tract in adult female one-humped camel (Camelus dromedarius) kept in the natural environment of Pakistan. A total 25 reproductive tracts were collected during spring, summer, autumn and winter seasons and were analysed for histo-morphometric parameters during different environmental conditions. A significant increase in number (p<0.05) and size (p<0.05) of surface with secondary and tertiary ovarian follicles was observed in winter season. The epithelial height (p<0.05) and luminal diameter (p<0.05) of infundibulum, ampulla and isthmus of uterine tubes were also significantly increased during winter season. Moreover, significantly increased length (p<0.05) and circumference (p<0.05) of uterine cornua, increased number (p<0.001) and diameter (p<0.001) of endometrial glands with enlarged surface and glandular epithelia (p<0.001) were found in winter compared to summer season. Therefore, we concluded that quiescent ovarian follicular and uterine glandular activities are the main reason of camel low breeding during summer season.


Excitatory effects of fentanyl upon the rat electroencephalogram and auditory-evoked potential responses during anaesthesia.
Previous studies have shown existence of inconsistent data concerning the use of auditory-evoked potential (AEP) and electroencephalogram (EEG) changes to measure the depth of anaesthesia in regimens involving the use of opioids. The present studies characterize the effects of fentanyl on those responses in rats. The effects of a bolus of fentanyl (6-10 microg kg(-1) intravenously) alone or following naloxone (100 microg kg(-1) intravenously) were examined using brain responses in rats during light anaesthesia with either propofol (20-30 mg kg(-1) h(-1)) or isoflurane (0.8%). Electrophysiological data were recorded using silver ball electrodes. The rats' tracheas were intubated and a femoral artery cannula was inserted to monitor blood pressure. Body temperature, respiratory and pulse rate, and pedal withdrawal data were also collected. Parameters measured before and following administration of naloxone and fentanyl or of fentanyl alone were compared using repeated-measures ANOVA. Fentanyl significantly increased the latency of the major peak from the AEP during propofol and isoflurane anaesthesia (F = 13.2 and 13.5, respectively; P < 0.05) and the amplitude differential between two waveform complexes, and the second differential index (F = 28.3 and 57.2, respectively; P < 0.01). The spectral edge frequency and median frequency from the EEG tended to increase. These effects were abolished by the prior administration of naloxone. These excitatory effects were inconsistent with the classical concept of brain activity depression indicating a deepening of anaesthesia.


Provider Tools for Advance Care Planning and Goals of Care Discussions: A Systematic Review.
Advance care planning and goals of care discussions involve the exploration of what is most important to a person, including their values and beliefs in preparation for health-care decision-making. Advance care planning conversations focus on planning for future health care, ensuring that an incapable person's wishes are known and can guide the person's substitute decision maker for future decision-making. Goals of care discussions focus on preparing for current decision-making by ensuring the person's goals guide this process. To provide evidence regarding tools and/or practices available for use by health-care providers to effectively facilitate advance care planning conversations and/or goals of care discussions. A systematic review was conducted focusing on guidelines, randomized trials, comparative studies, and noncomparative studies. Databases searched included MEDLINE, EMBASE, and the proceedings of the International Advance Care Planning Conference and the American Society of Clinical Oncology Palliative Care Symposium. Although several studies report positive findings, there is a lack of consistent patient outcome evidence to support any one clinical tool for use in advance care planning or goals of care discussions. Effective advance care planning conversations at both the population and the individual level require provider education and communication skill development, standardized and accessible documentation, quality improvement initiatives, and system-wide coordination to impact the population level. There is a need for research focused on goals of care discussions, to clarify the purpose and expected outcomes of these discussions, and to clearly differentiate goals of care from advance care planning.


Arabidopsis ETHE1 encodes a sulfur dioxygenase that is essential for embryo and endosperm development.
Mutations in human (Homo sapiens) ETHYLMALONIC ENCEPHALOPATHY PROTEIN1 (ETHE1) result in the complex metabolic disease ethylmalonic encephalopathy, which is characterized in part by brain lesions, lactic acidemia, excretion of ethylmalonic acid, and ultimately death. ETHE1-like genes are found in a wide range of organisms; however, the biochemical and physiological role(s) of ETHE1 have not been examined outside the context of ethylmalonic encephalopathy. In this study we characterized Arabidopsis (Arabidopsis thaliana) ETHE1 and determined the effect of an ETHE1 loss-of-function mutation to investigate the role(s) of ETHE1 in plants. Arabidopsis ETHE1 is localized in the mitochondrion and exhibits sulfur dioxygenase activity. Seeds homozygous for a DNA insertion in ETHE1 exhibit alterations in endosperm development that are accompanied by a delay in embryo development followed by embryo arrest by early heart stage. Strong ETHE1 labeling was observed in the peripheral and chalazal endosperm of wild-type seeds prior to cellularization. Therefore, ETHE1 appears to play an essential role in regulating sulfide levels in seeds.


Use of Different Food Image Recognition Platforms in Dietary Assessment: Comparison Study.
In the domain of dietary assessment, there has been an increasing amount of criticism of memory-based techniques such as food frequency questionnaires or 24 hour recalls. One alternative is logging pictures of consumed food followed by an automatic image recognition analysis that provides information on type and amount of food in the picture. However, it is currently unknown how well commercial image recognition platforms perform and whether they could indeed be used for dietary assessment. This is a comparative performance study of commercial image recognition platforms. A variety of foods and beverages were photographed in a range of standardized settings. All pictures (n=185) were uploaded to selected recognition platforms (n=7), and estimates were saved. Accuracy was determined along with totality of the estimate in the case of multiple component dishes. Top 1 accuracies ranged from 63% for the application programming interface (API) of the Calorie Mama app to 9% for the Google Vision API. None of the platforms were capable of estimating the amount of food. These results demonstrate that certain platforms perform poorly while others perform decently. Important obstacles to the accurate estimation of food quantity need to be overcome before these commercial platforms can be used as a real alternative for traditional dietary assessment methods.


Bone marrow-derived mesenchymal stem cells co-cultured with pancreatic islets display β cell plasticity.
The direct co-culturing effect of rat bone-marrow-derived mesenchymal stem cells (rBM-MSCs) on the pancreatic-islets (PIs) was studied to obtain functional islet cells. MSCs were isolated from rat bone marrow and cultivated under standard conditions. Following their characterization, the rBM-MSCs were directly (with cell-islet contact) co-cultured with recovered PIs together with the single cell cultures of those cell cultures as a control. The effect of direct co-cultures of rBM-MSCs with the PIs of normal rats was investigated using immunophenotypical and functional methods. The change in the amount of insulin secretion was evaluated as an indicator for differentiation of rBM-MSCs. One approache for in vitro differentiation to achieve reprogramming for differentiation into suitable cell types by changing the microenvironment of the cells to provide signals that might activate metabolic pathways is to use co-cultures with the microenvironment of the specific cells of the desired cell type, tissue/organ extracts, extracellular matrix compounds or biologically absorbable materials. Differentiated rBM-MSCs were found to be immunopositive for the specific insulin-producing cell marker, insulin, but not in undifferentiated rBM-MSCs. The functionality tests by ELISA confirmed that insulin secretion of co-cultured MSCs with islets was higher than that of islets. These evidences indicated that PIs could be regarded as critical components of the stem cell niche, such that MSCs can be differentiated into insulin-producing cells (IPCs). Moreover, direct cell-to-cell contact might provide additional and independent support. This approach would circumvent the need for PI-stem cell co-culture and could potentially facilitate the production of functional IPCs for future clinical applications.


The influence of body position on Bielschowsky's test.
To investigate the veracity of Jampolsky's statement that Bielschowsky's head tilt test is inverted if performed with the patient in the upside-down position and to interpret its neuromuscular mechanism. We present a series of 10 patients selected from a referred sample who were diagnosed with superior oblique paresis. Hypertropia was measured in the primary position, with the head erect and tilted toward both shoulders with the patient in the erect, supine, and upside-down positions. The last position was achieved by hanging the patient upside-down. As expected, our results showed the veracity of Jampolsky's statement. The forced head tilt difference was inverted or significantly decreased when the test was performed in the upside-down position. Moreover, in all patients, Bielschowsky's phenomenon was neutralized in the supine body position, in which hypertropia with the head erect tended to vanish. In 3 patients, it disappeared completely. This study showed that, in patients with superior oblique paresis, differences in the extent of hypertropia in Bielschowsky's test tended to vanish when the test was performed with the patient in the supine position and invert when it was performed with the patient in the upside-down position.


Deep vein thrombosis in lumbar spinal fusion: a prospective study of antiembolic and pneumatic compression stockings.
We prospectively studied the incidence of deep vein thrombosis (DVT) of the thigh in 117 patients having posterior lumbar spinal fusion with instrumentation and bone grafting for degenerative disk disease or spondylolisthesis. Patients with neoplasm, infection, trauma, or history of DVT were excluded. Patients were randomized into two groups. In the operating room, group 1 patients were placed in thigh-high antiembolic compression stockings (TED hose), and group 2 patients were placed in antiembolic stockings and pneumatic compression stockings. In both groups, the stockings were used until discharge. Postoperatively, patients in both groups received 600 mg buffered aspirin twice daily. Comparative analysis of the two groups showed no difference in operative time, blood loss, number of levels of lumbar vertebrae fused, time to mobilization, weight, age, or sex. All patients had duplex scanning of the thigh postoperatively. No patient in the series was observed to have acute DVT by clinical examination or by ultrasonography.


Oxidation of troglitazone to a quinone-type metabolite catalyzed by cytochrome P-450 2C8 and P-450 3A4 in human liver microsomes.
Troglitazone, a new oral antidiabetic drug, is reported to be mostly metabolized to its conjugates and not to be oxidized by cytochrome P-450 (P-450) enzymes. Of fourteen cDNA-expressed human P-450 enzymes examined, CYP1A1, CYP2C8, CYP2C19, and CYP3A4 were active in catalyzing formation of a quinone-type metabolite at a concentration of 10 microM troglitazone, whereas CYP3A4 had the highest catalytic activity at 100 microM substrate. In human liver microsomes, rates of the quinone-type metabolite formation (at 100 microM) were correlated well with rates of testosterone 6beta-hydroxylation (r = 0.98), but those at 10 microM troglitazone were not correlated with any of several marker activities of P-450 enzymes. Quercetin efficiently inhibited quinone-type metabolite formation (at 10 microM troglitazone) in human samples that contained relatively high levels of CYP2C, whereas ketoconazole affected these activities in liver microsomes in which CYP3A4 levels were relatively high. Anti-CYP2C antibodies strongly inhibited quinone-type metabolite formation (at 10 microM troglitazone) in CYP2C-rich human liver microsomes (by approximately 85%); the intensity of this effect depended on the human samples and their P-450 status. The results suggest that in human liver both CYP2C8 and CYP3A4 have major roles in quinone-type metabolite formation and that the hepatic contents of these two P-450 forms determine which P-450 enzymes play major roles in individual humans. CYP3A4 may be expected to play a role in formation of quinone-type metabolite from troglitazone even at a low concentration in humans.


Hashimoto's thyroiditis.
Goiters were often associated with iodine deficiency in European mountain areas, with some goiters being quite disfiguring. However, some goiters seem not to be related to iodine deficiency. One of the types of goiter that are unrelated to iodine deficiency is the disease described by Hakaru Hashimoto in 1912. Hashimoto described it as a special characteristic of a new type of lymphomatous thyroid tumor in Japan, and this entity was recognized as an autoimmune disease of the thyroid many years later. Hashimoto published his article in a German journal because that was the scientific language of the time, and he thought that writing in German would make the work more widely available around the world. Patients with Hashimoto's thyroiditis are usually asymptomatic, and some patients develop goiters with or without hypothyroidism. The goiters and hypothyroidism usually respond to treatment with thyroid hormone. The dose of thyroid hormone must be carefully titrated because there may be autonomous thyroid function resulting from thyroid-stimulating antibodies despite the hypothyroid state.


Co-trimoxazole and azathioprine: a safe combination.
Ninety-four patients receiving immunosuppressive therapy with azathioprine and prednisone after human cadaver kidney transplantation developed urinary tract infections and were treated with co-trimoxazole or another antibiotic in a controlled randomized prospective trial. The incidence of leucopenia in the group treated with co-trimoxazole (10.6%) was not significantly different from that in the group treated with other antibiotics (23.6%). Leucopenia when it occurred did so soon after transplantation at a time when the function of the renal transplant was poor in relation to the dosage of azathioprine given. In all cases the temporary withdrawal of azathioprine relieved the leucopenia despite continuation of the co-trimoxazole treatment. This study did not provide any evidence that co-trimoxazole plus azathioprine was a more potent cause of leucopenia than azathioprine alone.


Should yeasts in respiratory secretions be identified?
Four hundred forty samples of sputa and bronchial washings were examined microscopically for evidence of pulmonary and oropharyngeal secretions. Most (88%) sputa showed definite evidence of oropharyngeal contamination, whereas bronchial washings showed much less frequent (21%) contamination. Culture results of the same specimens showed that yeasts (excluding dimorphic fungi) were recovered from 74% of the sputa and 25% of the bronchial washings. It seems that microscopic evidence of oropharyngeal contamination is a reliable index for predicting the presence of yeasts in respiratory secretions. Their presence in cultures of respiratory secretions probably represents "normal flora" except for Cryptococcus neoformans, and their routine identification is not warranted.


Differential activity of two non-hr origins during replication of the baculovirus Autographa californica nuclear polyhedrosis virus genome.
The identification of potential baculovirus origins of replication (ori) has involved the generation and characterization of defective interfering particles that contain major genomic deletions yet retain their capability to replicate by testing the replication ability of transiently transfected plasmids carrying viral sequences in infected cells. So far, there has not been any evidence to demonstrate the actual utilization of these putative origins in Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) replication. By using the method of origin mapping by competitive PCR, we have obtained quantitative data for the ori activity of the HindIII-K region and the ie-1 promoter sequence in AcMNPV. We also provide evidence for differential activity of the two ori in the context of the viral genome through the replication phase of viral infection. Comparison of the number of molecules representing the HindIII-K and ie-1 origins vis-à-vis the non-ori polH region in a size-selected nascent DNA preparation revealed that the HindIII-K ori is utilized approximately 14 times more efficiently than the ie-1 region during the late phase of infection. HindIII-K also remains the more active ori through the early and middle replication phases. Our results provide in vivo evidence in support of the view that AcMNPV replication involves multiple ori that are activated with vastly different efficiencies during the viral infection cycle.


Primed antigen-specific CD4+ T cells are required for NK cell activation in vivo upon Leishmania major infection.
The ability of NK cells to rapidly produce IFN-gamma is an important innate mechanism of resistance to many pathogens including Leishmania major. Molecular and cellular components involved in NK cell activation in vivo are still poorly defined, although a central role for dendritic cells has been described. In this study, we demonstrate that Ag-specific CD4(+) T cells are required to initiate NK cell activation early on in draining lymph nodes of L. major-infected mice. We show that early IFN-gamma secretion by NK cells is controlled by IL-2 and IL-12 and is dependent on CD40/CD40L interaction. These findings suggest that newly primed Ag-specific CD4(+) T cells could directly activate NK cells through the secretion of IL-2 but also indirectly through the regulation of IL-12 secretion by dendritic cells. Our results reveal an unappreciated role for Ag-specific CD4(+) T cells in the initiation of NK cell activation in vivo upon L. major infection and demonstrate bidirectional regulations between innate and adaptive immunity.


Smiling reduces masculinity: principal component analysis applied to facial images.
We examined the effect of facial expression on the assignment of gender to facial images. A computational analysis of the facial images was applied to examine whether physical aspects of the face itself induced this effect. Thirty-six observers rated the degree of masculinity of the faces of 48 men, and the degree of femininity of the faces of 48 women. Half of the faces had a neutral facial expression, and the other half was smiling. Smiling significantly reduced the perceived masculinity of men's faces, especially for male observers, whereas no effect of smiling on femininity ratings was obtained for women's faces. A principal component analysis was conducted on the matrix of pixel luminance values for each facial image x all the images. The third principle component explained a relatively high proportion of the variance of both facial expressions and gender of face. These results suggest that the effect of smiling on the assignment of gender is caused, at least in part, by the physical relationship between facial expression and face gender.


Bycatch levies could reconcile trade-offs between blue growth and biodiversity conservation.
Economic activities in the ocean (that is, the 'blue economy') provide value to society, yet also jeopardize marine ecosystems. For example, fisheries are an essential source of income and food security for billions of people, yet bycatch poses a major threat to marine biodiversity, creating trade-offs between economic growth and biodiversity conservation. This Perspective explores bycatch levies as a market-based instrument for reconciling these trade-offs. We outline the theory and practice of bycatch levies to demonstrate how they could incentivize bycatch prevention and raise revenue for compensatory conservation, provided they are well designed, as part of a policy mix for sustainable and equitable ocean governance. We then explore ways forward for mainstreaming bycatch levies into the blue economy. While compensatory bycatch mitigation has been controversial, increasing adoption of net outcome approaches to biodiversity conservation suggests they could become mainstreamed within the next decade. Bycatch levies could raise billions of dollars towards closing global biodiversity financing gaps, delivering net outcomes for biodiversity under the United Nations Post-2020 Global Biodiversity Framework while enabling blue growth, and moving towards win-wins for economic welfare and biodiversity conservation.


Feeding habits of alfonsino Beryx splendens.
The diet of the alfonsino Beryx splendens was determined from examination of stomach contents of 287 specimens of 17 to 48 cm fork length (L(F)) sampled by bottom trawl on the Chatham Rise to the east of New Zealand. Prey items were predominantly crustaceans and mesopelagic fishes. The most important prey species by mass was Sergestes spp. prawns, followed by the myctophid Lampanyctodes hectoris, and then Pasiphaea spp. prawns. Multivariate analyses indicated that small crustaceans (euphausiids and amphipods) were most important in the diet of smaller B. splendens (100-424 g, 17-26.5 cm), with larger prawn species and mesopelagic fishes most important for larger fish (425-2070 g, 27-46 cm). Moon phase and bottom temperature also explained some of the variability in diet, but the moon phase effect was difficult to explain, and the bottom temperature effect may have been confounded, to some extent, with L(F). The results indicated that B. splendens were moderately selective feeders that foraged primarily in the mesopelagic layers. The diet of New Zealand B. splendens is generally similar to those reported from other areas, i.e. dominated by mesopelagic crustaceans and fishes, and with a transition from small crustaceans to fishes with increasing predator size.


The lack of association between dietary antioxidant quality score with handgrip strength and handgrip endurance amongst Tehranian adults: A cross-sectional study from a Middle East country.
The association between dietary antioxidant quality score (DAQS) and handgrip strength (HS) and handgrip endurance (HE) is still unclear. We aimed to investigate whether adherence to dietary antioxidant quality score (DAQS) is associated with handgrip strength (HS) and handgrip endurance (HE) amongst adults in Tehran. This cross-sectional study was conducted on 270 (43.7% males, mean age 37 years and 56.3% females, mean age 35 years) apparently healthy adult subjects (53.2% were married) selected from different parts of Tehran, Iran. Dietary intake was assessed using a 168-item validated food frequency questionnaire. DAQS was calculated using antioxidant-nutrient intake. Body composition was measured using a body composition analyser. Handgrip strength and endurance were measured by a digital handgrip dynamometer. Relative muscle strength was expressed as the ratio of handgrip strength by body mass index (BMI). The results showed that DAQs had no significant association with HS (P = .67, adjusted R2 = .60) and HE (P = .19, adjusted R2 = .08) after adjusting for potential confounders. However, a significant positive association was found between selenium intake and HE even after adjusting for potential confounders (P = .01, adjusted R2 = .10). After controlling for potential confounders no differences in the mean of HS (P = .29) and also HE (P = .61) amongst tertiles of DAQS was found. Positive linear association was found between vitamin C (P = .02, adjusted R2 = .53) and vitamin E (P = .03, adjusted R2 = .55) intake with relative muscle strength. Our results revealed that no significant association between DAQS and HE and HS. It was found that more intake of selenium was positively linked to HE. Dietary intake of vitamin C and vitamin E are associated with higher relative muscle strength. It is evident that more prospective studies are needed to confirm the veracity of our results.


[On perinatal and infant mortality in the Arkhangelsk Region].
Perinatal and infant mortality in the Arkhangelsk Region tends to decline. At the same time, the structure of perinatal mortality shows a significant increase in the proportion of congenital defects, among which multiple forms constitute a major portion. The most common causes of infant death are acute respiratory infections, congenital malformations, and sudden infant death syndrome.


Bacterial lipopolysaccharide causes rapid shedding, followed by inhibition of mRNA expression, of the IL-1 type II receptor, with concomitant up-regulation of the type I receptor and induction of incompletely spliced transcripts.
The IL-1 type I receptor (IL-1RI) is part of a signaling complex together with the IL-1R accessory protein, whereas available information is consistent with a "decoy" model of function for the IL-1 type II receptor (IL-1RII). The present study was designed to investigate the effect of bacterial LPS on IL-1R in human monocytes. LPS causes rapid release of the IL-1RII, an effect blocked by a metalloprotease inhibitor. Subsequently, LPS-treated monocytes showed a drastic reduction of IL-1RII mRNA. In contrast, LPS induced IL-1RI and, to a lesser extent, IL-1AcP expression. LPS-induced augmented expression of the canonical 5-kb IL-1RI mRNA was accompanied by the appearance of 2.4-kb IL-1RI transcripts. The use of probes representative of different regions of the IL-1RI mRNA, as well as cDNA cloning, revealed that the 2.4-kb inducible band includes incompletely spliced, polyadenylated transcripts potentially encoding truncated versions of the receptor. The observation that the prototypic proinflammatory molecule LPS has divergent effects on IL-1Rs, with inhibition of IL-1RII and stimulation of IL-1RI and IL-1R accessory protein, is consistent with the view that these molecules subserve opposite functions in the pathophysiology of the IL-1 system. The rapid shedding of IL-1RII by monocytes early in recruitment may serve to buffer the systemic action of IL-1 leaking from sites of inflammation. This early event, followed by prolonged inhibition of IL-1RII expression and up-regulation of IL-1RI, may render monocytes more responsive to IL-1 at sites of inflammation.


[Size frequency distribution and growth of the crabs Callinectes arcuatus and C. bellicosus (Decapoda: Portunidae) in Las Guásimas coastal lagoon, Mexico].
Information on size frequency distribution, the width-weight relation and growth parameters of the crabs Callinectes arcuatus and C. bellicosus is presented. The data comes from samples taken with a trawl net both day and night on a monthly basis from March 1998 to February 2000 in a coastal lagoon from Gulf of California. C. bellicosus (n=878) was more abundant than C. arcuatus (n=357) and its size frequency distribution presented carapace width CW ranges of 8.4-166 mm and 9-130 mm respectively. Both populations were mainly represented by juveniles (75 mm in CW) ranging from 37 to 75 mm in CW, and adults (>75 mm in CW) between 76 and 90 mm in CW. In both species the width-weight relation showed that males grow more than females, with an isometric growth tendency being observed. The growth parameters for C. arcuatus estimated using the von Bertalanffy Model, were: K = 0.84 year(-1), L infinity = 140 mm to = -0.12 for C. arcuatus, and K= 0.9 year(-1), L infinity = 169 mm to = -0.11 for C. bellicosus. These results showed that the relative age at which maximum growth is attained is between three and four years for both species.


[Apparent life threatening event (ALTE): the role of the training in the follow-up].
The aim of this study was to give a support to the parents of the patients with apparent life threatening event (ALTE), to learn a correct management outside the protective environment of the hospital and a prevention such events. This was the 33rd edition of a training course called "Course of first aid and prevention of the accidents in infants", in which the recommendations of the Italian cardiopulmonary resuscitation's guidelines are treated. The course comprehended a short frontal lesson, a practice training and the compilation of a test to express one's satisfaction about the received training, using a points assessment from 1 to 10. The course included 385 participants (including any kind of person who may be in contact with infants) and 361 questionnaires were returned. Critical parameters were the scheme of teaching, the adequacy of contents, the teachers' technical and behavioral abilities, the adequacy of time and the communicative capacity. The learners demonstrated pleasure in variable percentages from 98% to 100%. The 79% of the learners felt the necessity to have some training again later on. Our positive experience allowed us to reflect about three concepts that we considered essential: communication, training and prevention. In fact, we think that prevention is infinitely potentiated from training and communication is its inalienable instrument.


Adolescent survivors after suicide: Australian young people's bereavement narratives.
While the research literature exploring suicide bereavement has expanded in recent years, this has been primarily quantitative and has focused more on the bereavement experience of parents and siblings. The bereavement experience of young people affected through the suicide death of a friend remains under-conceptualized and not well understood. To develop an understanding of the experiences of young people bereaved by the suicide of a friend. Ten young people participated in a pilot study with in-depth interviews to explore their suicide bereavement experiences. Narrative inquiry methodology was utilized to analyze the qualitative data. The findings indicated multiple grief experiences caused by suicide. Four themes reported are meaning making, feeling guilt, risky coping behavior, and relating to friends following suicide loss. Implications include the need for increased awareness that friends of young people who die by suicide may have significant health and well-being challenges associated with bereavement, and that friends in these circumstances may not readily present at services for assistance.


Solar tracking by plants.
Leaves of many desert and agricultural species have the ability to move diurnally, orienting perpendicular or parallel to the sun's direct rays. This phenomenon is widespread in many plant families and occurs in both C(3) and C(4) photosynthetic pathway plants. In the annual flora of desert communities, solar tracking becomes more frequent as the length of the growing season decreases. Leaves that are perpendicular to the sun's direct rays for tracking appear to have high photosynthetic rates throughout the day, whereas leaves parallel to the sun's rays have reduced leaf temperatures and transpirational water losses.


Recombinant modified vaccinia virus Ankara expressing a soluble form of glycoprotein B causes durable immunity and neutralizing antibodies against multiple strains of human cytomegalovirus.
Human cytomegalovirus (CMV) is a viral pathogen that infects both genders, who remain asymptomatic unless they receive immunosuppressive drugs or acquire infections that cause reactivation of latent virus. CMV infection also causes serious birth defects following primary maternal infection during gestation. A safe and effective vaccine to limit disease in this population continues to be elusive. A well-studied antigen is glycoprotein B (gB), which is the principal target of neutralizing antibodies (NAb) towards CMV in humans and has been implicated as the viral partner in the receptor-mediated infection by CMV in a variety of cell types. Antibody-mediated virus neutralization has been proposed as a mechanism by which host immunity could modify primary infection. Towards this goal, an attenuated poxvirus, modified vaccinia virus Ankara (MVA), has been constructed to express soluble CMV gB (gB680-MVA) to induce CMV NAb. Very high levels of gB-specific CMV NAb were produced after two doses of the viral vaccine. NAb were durable within a twofold range for up to 6 months. Neutralization titers developed in immunized mice are equivalent to titers found clinically after natural infection. This viral vaccine, expressing gB derived from CMV strain AD169, induced antibodies that neutralized CMV strains of three different genotypes. Remarkably, preexisting MVA and vaccinia virus (poxvirus) immunity did not interfere with subsequent immunizations of gB680-MVA. The safety characteristics of MVA, combined with the robust immune response to CMV gB, suggest that this approach could be rapidly translated into the clinic.


Glucocorticoids modulate human gonadotrophin releasing hormone upstream promoter activity in transfected human placental cells (JEG-3).
A human gonadotrophin releasing hormone (GnRH) upstream promoter/luciferase reporter gene construct (H2 construct) was generated by inserting a 1.7 kb XbaI/AflII fragment containing the human GnRH upstream promoter region only into a promoter-less luciferase reporter vector. When JEG-3 cells were transiently transfected with this construct and treated with cortisol or its synthetic analogue dexamethasone, a stimulatory effect on the upstream promoter activity was observed. This stimulation was dependent on the cotransfection of a glucocorticoid receptor (GR) cDNA expression vector due to the low level of GR in JEG-3 cells and could be completely abolished by RU486, a glucocorticoid antagonist. Moreover, the cortisol actions could be modulated to a different extent by oestradiol. Thus, since the human placenta contains GRs and the increase in cortisol metabolism near term is regulated by oestrogen, the current findings suggest that cortisol may be physiologically involved in the regulation of GnRH gene expression in the human placenta.


Bisulfite (sulfur dioxide) is a comutagen in E. coli and in Chinese hamster cells.
The mutagenic and comutagenic effects of bisulfite were investigated. Under moderate exposure conditions (high survival) it was found that bisulfite is not mutagenic to either eukaryotic cells (Chinese hamster V79), or prokaryotic cells (Escherichia coli). However, bisulfite does act as a comutagen with UV irradiation. Bisulfite approximately doubles the mutation frequency in UV-irradiated Chinese hamster V79 cells, and it causes a greater than 8-fold increase in Trp+ revertants in UV-irradiated E. coli. The comutagenic effect occurs whether cells are exposed to bisulfite during or immediately after UV irradiation. Kinetic studies of the comutagenic effect in E. coli shows that it decays in a biphasic manner, with an apparent half-life of 15 min and a persistence of the comutagenic effect for up to 120 min after UV irradiation. Experiments with several strains of E. coli of varying DNA-repair capacities indicate that excision repair is necessary for a comutagenic effect by bisulfite. It is thought that bisulfite acts to inhibit excision repair, perhaps by effects on DNA polymerase I, or DNA ligase.


Symptomatic splenoma (hamartoma) of the spleen. A case report.
Hamartomas of the spleen (splenomas) are very rare benign tumors composed of an aberrant mixture of normal splenic elements. Herein we present a unique case of a symptomatic non-palpable splenoma in a 64-year-old female patient presented with anemia and thrombocytopenia and we describe imaging findings in ultrasound, computed tomography and magnetic resonance imaging. To our knowledge, this is the first case of a relatively small splenic hamartoma (35 mm at histopathology) associated with thrombocytopenia and anemia that resolved completely several months after splenectomy.


[The nerve centers of the emotions].
The participation and the role of the brain formations in the genesis of emotional reactions of higher animals and man are discussed according to E.A. Asratian's concept of the nervous centre as a complex of brain structures, situated in different areas of the central nervous system, comprising the total morpho-functional unity and realizing a definite specific function. The data are given testifying that the frontal and temporal areas of the neocortex, hippocampus, amygdala and hypothalamus are correspondingly connected with reflecting-estimating, compensatory, transferring and reinforcing functions of emotions. The reinforcing function is phylogenetically the most ancient. It is connected with solution of the universal behavioural task of maximization-minimization of the appeared emotion, striving for "to" or "from". Replacing and transferring functions have been formed later, while reflecting-estimating one is the most young. It namely provides the wealth and diversity of emotions, based on complicated vital, social and cognitive needs. Such succession coincides with the evolution of the corresponding brain formations, with their phylogenetic age.


Are total, intensity- and domain-specific physical activity levels associated with life satisfaction among university students?
Thorough information about the relationship between physical activity (PA) and life satisfaction is still lacking. Therefore, this study examined the cross-sectional relationships between life satisfaction and meeting the World Health Organization (WHO) moderate to vigorous-intensity PA recommendations, total volume and duration of PA, intensity-specific PA (walking, moderate- and vigorous-intensity), domain-specific PA (work, transport-related, domestic, and leisure-time), and 11 domain and intensity-specific PA types among university students. Additionally, we examined the associations between life satisfaction and gender, age, disposable income, community size, smoking, alcohol intake, body mass index (BMI), and self-rated health. The study included a random sample of 1750 university students in Zagreb, Croatia (response rate = 71.7%; 62.4% females; mean age 21.5 ± 1.8 years), using the International Physical Activity Questionnaire-long form and the Satisfaction with Life Scale. Higher life satisfaction was associated with female gender (β = 0.13; p = <0.001), younger age (β = -0.07; p = 0.024), higher disposable income (β = 0.10; p = 0.001), and better self-rated health (β = 0.30; p = <0.001). No significant association was found between life satisfaction and size of community (p = 0.567), smoking status (p = 0.056), alcohol consumption (p = 0.058), or BMI (p = 0.508). Among all PA variables, only leisure-time vigorous-intensity PA was significantly associated with life satisfaction after adjustments for socio-demographic characteristics, lifestyle and self-rated general health (β = 0.06; p = 0.045). This study indicated a weak positive relationship between leisure-time vigorous-intensity PA and life satisfaction, whilst no such association was found for other PA variables. These findings underscore the importance of analyzing domain and intensity-specific PA levels in future studies among university students, as drawing conclusions about the relationship between PA and life satisfaction based on total PA levels only may be misleading.


[New viewpoints on the pathogenesis and the treatment of strabismus. First part: pathogenesis of strabismus (author's transl)].
In 1962 the anteroposition of the inferior oblique muscle has been introduced. This surgery enlarges the angle between the muscle and the visual axis favouring the torsional action at the cost of the vertical one. The results of 554 cases with a postoperative follow-up of at least ten years are analysed. The spontaneous recovery of binocular vision and the disappearance of the accommodative component suggest that a sagittalization of the oblique muscles might be an important cause of strabismus. The evolution of the suppression scotoma demonstrates that the position of the eyes depends on the optomotor balance between the nasal and temporal retinal halves. A new concept of the pathogenesis of squint is presented. The sagittalization of the oblique muscles and the hemiretinal suppression are considered to be the keys by means of which the problem of strabismus could be solved.


Lysophosphatidic acid and mesangial cells: implications for renal diseases.
The last decade has witnessed a phenomenal increase in our understanding of the biological role of lysophosphatidic acid (LPA) and has led to an appreciation of this critical serum-derived growth factor released from platelets. We herein summarize recent observations that collectively support the hypothesis that LPA may play a key role in the pathogenesis of initiation and progression of proliferative glomerulonephritis. LPA synergistically stimulates mesangial cell proliferation in combination with platelet-derived growth factor in primary culture. The mechanism of co-mitogenesis is likely to be mediated by the prolonged activation of mitogen-activated protein kinase which is stimulated by platelet-derived growth factor and LPA through different mechanisms. LPA contracts cultured mesangial cells and has properties in common with other pressor molecules including mobilization of intracellular Ca2+ and promotion of Ca2+ entry through dihydropyridine-sensitive calcium channels. LPA receptor mRNA has been identified in isolated glomeruli dissected from renal biopsy samples of patients with IgA nephropathy. All of these facts have led us to postulate that LPA is produced within glomeruli and that LPA's mitogenic as well as haemodynamic action contribute to the pathological process of mesangial proliferative glomerulonephritis. The possible production of LPA as an autocrine factor from mesangial cells themselves has also been discussed.


Microbial volatile emissions as insect semiochemicals.
We provide a synthesis of the literature describing biochemical interactions between microorganisms and insects by way of microbial volatile organic compound (MVOC) production. We evaluated the functionality and ecological context of MVOC signals, and explored important metabolic pathways involved in MVOC production. The cosmopolitan distribution of microorganisms creates a context for frequent, and frequently overlooked, insect responses to microbial emissions. There are numerous instances of MVOCs being closely associated with insect feeding behaviors, but some MVOCs are also powerful repellants. Emissions from microorganisms in situ may signal aspects of habitat suitability or potential exposure to entomopathogens. In some ecosystems, bacterial or fungal volatiles can also incite insect aggregations, or MVOCs can resemble sexual pheromones that elicit mating and oviposition behaviors from responding insects. A single microorganism or MVOC can have different effects on insect behaviors, especially across species, ontogenies, and habitats. There appears to be a multipartite basis for insect responses to MVOCs, and complex tritrophic interactions can result from the production of MVOCs. Many biochemical pathways for behaviorally active volatile production by microbial species are conserved across large taxonomic groupings of microorganisms. In addition, there is substantial functional redundancy in MVOCs: fungal tissues commonly produce polyketides and short-chain alcohols, whereas bacterial tissues tend to be more commonly associated with amines and pyrazines. We hypothesize that insect olfactory responses to emissions from microorganisms inhabiting their sensory environment are much more common than currently recognized, and that these signals represent evolutionarily reliable infochemicals. Insect chemoreception of microbial volatiles may contribute to the formation of neutral, beneficial, or even harmful symbioses and provide considerable insight into the evolution of insect behavioral responses to volatile compounds.


Glycemic Management of Hospitalized Patients Receiving Nutrition Support.
Enteral nutrition (EN) and parenteral nutrition (PN) increase the risk of hyperglycemia and adverse outcomes, including mortality, in patients with and without diabetes. A blood glucose target range of 140-180 mg/dL is recommended for hospitalized patients receiving artificial nutrition. Using a diabetes-specific EN formula, lowering the dextrose content, and using a hypocaloric PN formula have all been shown to prevent hyperglycemia and associated adverse outcomes. Insulin, given either subcutaneously or as a continuous infusion, is the mainstay of treatment for hyperglycemia. However, no subcutaneous insulin regimen has been shown to be superior to others. This review summarizes the evidence on and provides recommendations for the treatment of EN- and PN-associated hyperglycemia and offers strategies for hypoglycemia prevention. The authors also highlight their institution's protocol for the safe use of insulin in the PN bag. Randomized controlled trials evaluating safety and efficacy of targeted insulin therapy synchronized with different types of EN or PN delivery are needed.