The VGF-derived peptide TLQP-21: a new modulatory peptide for inflammatory pain.
Vgf, is a neuro-endocrine specific gene encoding for a large protein precursor of different peptides. A role for VGF in pain modulation has been suggested from immunohistochemical studies showing VGF mRNA widely expressed in primary sensory neurons. In this study, the presence of VGF on the primary sensory afferents in mice was confirmed by showing its immunostaining in cultured neurons of dorsal root ganglia in secretory granule varicosities colocalized with Substance P. Moreover, the functional role of a C-terminal internal VGF-derived peptide, i.e. TLQP-21, was assessed by investigating its peripheral (1, 2, 4, 8mM) and central (1, 2, 4 mM) effects on inflammatory pain in the formalin test. A significant increase of pain-related licking response following peripheral injection of TLQP-21 (4 and 8mM) was observed in the second inflammatory phase of the test. In addition, an increase in licking response was detected when 4 mM of the peptide was injected alone without formalin. On the other hand, the central administration of TLQP-21 induced an U-shaped curve, with the dose of 2 mM being analgesic during the second phase. This study shows for the first time that a VGF-derived peptide may be involved in inflammatory pain in vivo and demonstrates a different action for TLQP21 at the peripheral and central levels of the nociceptive pathways.


Age, subjective life expectancy, and the sense of control: the horizon hypothesis.
This article reports a test of the horizon hypothesis, which states that greater subjective life expectancy increases the sense of control over one's own life and in part accounts for the negative association between age and the sense of control. Results of a U.S. survey of 2,029 respondents aged 18 and older (934 aged 50 and older) support the hypothesis. Subjective life expectancy has a significant positive association with the sense of control that does not vanish with adjustment for race, sex, education, income, widowhood, inability to work because of a disability, physical impairment, and physical fitness. Adjustment for subjective life expectancy explains the part of the negative association between age and the sense of control that remains after adjustment for education and physical impairment. Adjusting the three factors together explains 93.1 percent of the total association between age and the sense of control, and renders the remaining association insignificant.


The learning environment of four undergraduate health professional schools: Lessons learned.
Learning is an interplay between cognition and environmental factors. Any learning environment, that fulfills the intrinsic and extrinsic needs of the students will probably lead to better and more promising learning outcomes. This study aimed to investigate the student perceptions of Learning Environment (LE) in four health schools of a large university and compare between schools, years of study, and gender. Dundee Ready Education Environment Measure (DREEM) questionnaire and a socio-demographic questionnaire were completed by 1185 undergraduate students enrolled in the school of Medicine, Dentistry, Nursing and Applied Medical Sciences (AMS) of a large university during the academic year 2012-2013. Chi-square test was used to compare categorical variables. Independent student t-test or ANOVA (with Tukey post-hoc test) was used for continuous variables at a significance level of p≤0.05. The mean total DREEM score was 89.23±33.3. The total DREEM mean scores for Dentistry (120.54±23.45) and Medicine (110.72±19.33) were higher compared with AMS (63.48±21.36) and Nursing (57.48±22.80) (p=0.000) (Post hoc Tukey p=0.000). First year students gave significantly higher positive perceptions ratings than the rest of the years (p=0.000). Total scores were significantly higher for male (92.78±33.86) than female students (84.70±32.25) p=0.000. The LE significantly differed by year and gender. The students from non-integrated curricula (nursing and AMS) perceived the LE less positively than their integrated curriculum counterparts (medicine and dentistry). A qualitative study is needed to investigate the variation in the perception of LE among these groups.


Chemically induced growth inhibition and cell cycle perturbations in cultures of differentiating rodent embryonic cells.
Ethylnitrosourea (ENU) is a proven animal teratogen, although the mechanism of its developmental toxicity is unknown. The micromass rat embryo midbrain (CNS) and limb bud (LB) cultures were used in an effort to determine potential mechanisms by which ENU may exert its teratogenic effect. When cultured at high cell densities, both cell types undergo several rounds of replication while differentiating into discrete foci of neuronal cells and chondrocytes, respectively. Differentiation was monitored after 5 days by staining with hematoxylin (CNS) and alcian blue (LB). Our objectives were to (1) apply flow cytometry technology to the micromass cultures and (2) determine how ENU disrupts the normal growth, differentiation, and cell cycling of these cultures. Dose-dependent decreases in cell attachment and viability were observed in the first 24 hr after ENU exposure. Exposed cultures also exhibited dose-dependent growth inhibition over 5 days in culture as determined by cell counts. Flow cytometric cell cycle analysis of treated cultures revealed a dose-related accumulation of CNS cells in late G1/early S. Treated LB cells also displayed dose-related cell cycle changes with cells accumulating throughout the S phase. The concentration-dependent changes in both the CNS and the LB cell cycle profiles were observed in the attached cell populations which had greater than 94 +/- 3% viability at all ENU concentrations tested. This suggests that flow cytometric analysis allowed description of cellular alterations that would have been overlooked if only cell viability had been examined. Our examinations suggest that the effects of ENU on cell differentiation are related to its early effects on cell attachment, cell cycling, and cell proliferation.


A CO(2)-Flux Mechanism Operating via pH-Polarity in Hydrilla verticillata Leaves With C(3) and C(4) Photosynthesis.
The aquatic angiosperm Hydrilla verticillata lacks Kranz anatomy, but has an inducible, C(4)-based, CO(2) concentrating mechanism (CCM) that concentrates CO(2) in the chloroplasts. Both C(3) and C(4) Hydrilla leaves showed light-dependent pH polarity that was suppressed by high dissolved inorganic carbon (DIC). At low DIC (0.25 mol m(-3)), pH values in the unstirred water layer on the abaxial and adaxial sides of the leaf were 4.2 and10.3, respectively. Abaxial apoplastic acidification served as a CO(2) flux mechanism (CFM), making HCO (3) (-) available for photosynthesis by conversion to CO(2). DIC at 10 mol m(-3) completely suppressed acidification and alkalization. The data, along with previous results, indicated that inhibition was specific to DIC, and not a buffer effect. Acidification and alkalization did not necessarily show 1:1 stoichiometry; their kinetics for the apolar induction phase differed, and alkalization was less inhibited by 2.5 mol m(-3) DIC. At low irradiance (50 mumol photons m(-2) s(-1)), where CCM activity in C(4) leaves is minimized, both leaf types had similar DIC inhibition of pH polarity. However, as irradiance increased, DIC inhibition of C(3) leaves decreased. In C(4) leaves the CFM and CCM seemed to compete for photosynthetic ATP and/or reducing power. The CFM may require less, as at low irradiance it still operated maximally, if [DIC] was low. Iodoacetamide (IA), which inhibits CO(2) fixation in Hydrilla, also suppressed acidification and alkalization, especially in C(4) leaves. IA does not inhibit the C(4) CCM, which suggests that the CFM and CCM can operate independently. It has been hypothesized that irradiance and DIC regulate pH polarity by altering the chloroplastic [DIC], which effects the chloroplast redox state and subsequently redox regulation of a plasma-membrane H(+)-ATPase. The results lend partial support to a down-regulatory role for high chloroplastic [DIC], but do not exclude other sites of DIC action. IA inhibition of pH polarity seems inconsistent with the chloroplast NADPH/NADP(+) ratio being the redox transducer. The possibility that malate and oxaloacetate shuttling plays a role in CFM regulation requires further investigation.


Modelling of phospholipid translocation in the erythrocyte membrane: a combined kinetic and thermodynamic approach.
A mathematical model for the dynamics of transbilayer movements of lipids in the erythrocyte plasma membrane is presented. It takes into account an active carrier which mediates the ATP-dependent translocation of phosphatidylserine and phosphatidylethanolamine from the outer to the cytoplasmic leaflet of the membrane and passive fluxes of these lipids as well as of phosphatidylcholine, sphingomyelin and cholesterol between both layers. It is assumed that the passive fluxes are driven by concentration gradients of the lipids and by mechanical forces which result from area limitation for lipid occupation in both leaflets. Compared with a previous mathematical treatment of lipid translocation processes in the erythrocyte membrane the present model is much closer to realistic conditions, e.g. concerning the number of lipid species involved. Furthermore, the use of linear flux-force relationships as known from irreversible thermodynamics allows a simpler treatment of the passive fluxes than before and provides a relevant framework to study the coupling between the various processes. The model allows to simulate the time dependent changes of lipid concentrations which take place after activation or inhibition of ATP-dependent translocation. Using realistic parameter values it explains in quantitative terms the stationary asymmetric distribution of lipids under in vivo conditions. Using principles of metabolic control analysis we are able to quantify the role of the various active and passive processes in determining the asymmetric distribution for each lipid species.


A case of successful hormone therapy for refractory hypotension following viral encephalitis: Case report.
Refractory hypotension is a life-threatening condition that can result from various causes. We report a rare case of refractory hypotension following herpes simplex virus type 1 encephalitis that was successfully treated with hormone therapy. The patient was a 66-year-old male who was admitted to the hospital because of fever, chills, convulsions, and impaired consciousness. He developed respiratory failure and was intubated. Cerebrospinal fluid metagenomic sequencing confirmed herpes simplex virus type 1 infection. He received piperacillin-tazobactam for anti-infection, acyclovir for antiviral therapy, and dexamethasone for anti-inflammatory therapy. He had repeated episodes of hypotension despite fluid resuscitation and vasopressor therapy. The diagnosis of herpes simplex virus type 1 encephalitis complicated by refractory hypotension was based on the patient's epidemiological history, clinical manifestations, laboratory tests, and imaging studies. Cerebrospinal fluid examination was the most important diagnostic method, which could detect viral nucleic acids. Head magnetic resonance imaging showed a large recent lesion in the right temporal-parietal and insular lobes. The treatment of refractory hypotension mainly included anti-infection, antiviral, anti-inflammatory, and hormone therapy. Hormone therapy used methylprednisolone shock treatment until tapering withdrawal. Other treatments included fluid resuscitation, vasopressors, anticonvulsants, etc. The patient's blood pressure stabilized after receiving methylprednisolone shock treatment, and his mean arterial pressure increased from 73 mm Hg to 92 mm Hg within 24 hours. Three months later, the patient's blood pressure was normal without medication, and he had a good social and physical recovery. This case illustrates the possible role of hormone therapy in restoring blood pressure in patients with refractory hypotension following viral encephalitis. It suggests that adrenal insufficiency or autonomic dysfunction may be involved in the pathophysiology of this condition. Further studies are needed to confirm the efficacy and safety of hormone therapy in this setting.


Incidence of moral hazards among health care providers in the implementation of social health insurance toward universal health coverage: evidence from rural province hospitals in Indonesia.
To identify the incidence of moral hazards among health care providers and its determinant factors in the implementation of national health insurance in Indonesia. Data were derived from 360 inpatient medical records from six types C public and private hospitals in an Indonesian rural province. These data were accumulated from inpatient medical records from four major disciplines: medicine, surgery, obstetrics and gynecology, and pediatrics. The dependent variable was provider moral hazards, which included indicators of up-coding, readmission, and unnecessary admission. The independent variables are Physicians' characteristics (age, gender, and specialization), coders' characteristics (age, gender, education level, number of training, and length of service), and patients' characteristics (age, birth weight, length of stay, the discharge status, and the severity of patient's illness). We use logistic regression to investigate the determinants of moral hazard. We found that the incidences of possible unnecessary admissions, up-coding, and readmissions were 17.8%, 11.9%, and 2.8%, respectively. Senior physicians, medical specialists, coders with shorter lengths of service, and patients with longer lengths of stay had a significant relationship with the incidence of moral hazard. Unnecessary admission is the most common form of a provider's moral hazard. The characteristics of physicians and coders significantly contribute to the incidence of moral hazard. Hospitals should implement reward and punishment systems for doctors and coders in order to control moral hazards among the providers.


Relationship between clinical outcomes and vessel size in endovascular therapy for femoropopliteal lesions.
We investigated the relationship between the outcomes of endovascular therapy (EVT) for femoropopliteal (FP) lesions and vessel diameter. Several studies have reported a relationship between the outcome of EVT for FP lesions and lesion characteristics. However, the relationship with vessel diameter has not been explored. We retrospectively analyzed 2656 patients with 3340 de novo FP lesions (mean age, 73.9 ± 9 years; 70% male) who underwent EVT from January 2004 to December 2011. We classified the lesions into four groups according to the vessel diameter: group 1, ≤4 mm; group 2, 4 to 5 mm; group 3, 5 to 6 mm; and group 4, >6 mm. We investigated the relationship between the outcomes of EVT and vessel diameter. The primary outcome measure was restenosis, and the secondary outcome measures were target lesion revascularization and major adverse limb events. The restenosis rate at 3 years in group 1 was significantly higher compared with the other groups (62.2%, 35.7%, 37.1%, and 41.0% for groups 1, 2, 3, and 4, respectively; log-rank, P < .0001). The outcome among small vessels was significantly worse in the stent group, and the outcomes for target lesion revascularization and major adverse limb events were similar. After adjustment, a small vessel ≤4 mm remained an independent predictor of restenosis (hazard ratio, 1.69; 95% confidence interval, 1.44-1.98; P < .0001). This study suggested that vessel diameter, especially a small vessel ≤4 mm, was associated with poor EVT outcomes. The tendency was particularly evident in the stent group, which suggested that primary stenting should not necessarily be recommended for small vessels.


Inhibitory effects of histamine H1 receptor blocking drugs on metabolic activations of neutrophils.
Inhibitory effects of various histamine receptor-blocking agents including antiallergic agents on metabolic activations of neutrophils were examined by measuring leukotrienes (C4, D4 and E4) formation, arachidonic acid release and superoxide generation. The stimulation of neutrophils by calcium ionophore (A23187) causes the production of leukotrienes concomitantly with the release of arachidonic acid from the cells and these were effectively diminished with a variety of antihistaminic agents. Almost all the histamine H1 receptor-blocking drugs studied here showed as inhibitors of the metabolic activations of neutrophils, although the degree was dependent on the drug concentrations. The order of potency of the inhibitory effects on the arachidonic acid release were: homochlorcyclizine, clemastine, and azelastine (IC50 less than 20 microM) greater than oxatomide (IC50 less than 60 microM) and diphenylpyraline greater than triprolidine, meclizine, diphenhydramine (IC50 greater than 100 microM). The superoxide generation from neutrophils activated by phorbol 12-myristate 13-acetate was also effectively inhibited by these agents, but generally lower concentrations were required to obtain the same degrees of effects. These results indicated that some of the histamine H1 receptor-blocking drugs, such as clemastine and homochlorcyclizine, may act as inhibitors of formation of leukotrienes at the locus of inflammation.


Incidence of dental trauma among obese adolescents--a 3-year-prospective study.
The main objective of the present investigation was to estimate the incidence of traumatic dental injuries (TDI), in particular crown fractures in a 3-year follow-up of obese adolescents. Seven hundred and eighty-five 13-year-old school children were selected randomly. The crown fracture was classified according to Andreasen's criteria by visual examination without radiographs. Body mass index of the study subjects was determined. Increased overjet was considered as a risk factor when it presented values higher than 3 mm, while lip coverage was classified as adequate or inadequate. With appropriate sample weighting, relationships between TDI and other variables were assessed using the chi-squared test, Kruskal-Wallis H-test and multivariable logistic regression. At baseline, 131 (17.15%) adolescents presented with TDI. The accumulated incidence of TDI during the 3-year period of study was 9.03%. Children with obesity and overweight were 2.78 times greater chance suffering TDI after adjusting for socioeconomic status, lip coverage, incisal overjet and previous history of trauma. Both at baseline and follow-up examination, most frequently affected tooth is right maxillary central incisor and most frequent type of TDI was enamel fracture (44.68%). Adolescents with obesity and overweight were a greater chance of TDI in a 3-year follow-up.


Cross cultural adaptation, reliability and validity of the Polish version of the Cumberland Ankle Instability Tool.
Purpose: The aim of this study was to develop a Polish version of the Cumberland Ankle Instability Tool (CAIT-PL) questionnaire and perform CAIT-PL cultural adaptation with assessment of its psychometric properties.Methods: The original CAIT was translated into the Polish language using standard guidelines. The CAIT-PL was completed on 2 occasions by 105 participants both with and without a history of ankle sprains. Psychometric evaluation of CAIT-PL included an assessment of internal consistency, test-retest reliability, standard error of measurement, convergent and construct validity.Results: The CAIT-PL was successfully translated and adapted into Polish culture with satisfactory internal consistency (Cronbach's α = 0.83) and adequate test-retest reliability resulting in ICC2,1 = 0.89 (95% CI: 0.84-0.92). Measurement error was low (SEM = 0.76 and MDC = 2.10). Convergent validity of the CAIT-PL ranged from weak to strong using Spearman's correlation coefficient between CAIT-PL and FAOS subscales (r = 0.39-0.67; p < 0.05). Construct validity was confirmed.Conclusion: The Polish version of the Cumberland Ankle Instability Tool is a valid and reliable questionnaire for assessment of functional ankle instability among the Polish population.


An Ergonomic Assessment of Hospital Linen Bag Handling.
The Joint Commission provides accreditation standards for staging hospital waste, but there are no federal lifting safety standards for linen bags. We evaluated hospital laundry bag lifting using the Revised National Institute for Occupational Safety and Health (NIOSH) Lifting Equation. We hypothesized that the permitted 32-gallon linen container capacity might allow filling to weights above our calculated Recommended Weight Limit (RWL) for some lifting positions and contents. We found that 30- and 40-gallon bags filled with loose dry linen had predicted weights within estimated RWLs only for lifts close to the body. Thirty- and 40-gallon bags filled more than halfway with dry compact linen had predicted weights above estimated RWLs for all lifting positions. Thirty- and 40-gallon bags filled with wet compact linen exceeded estimated RWLs for all positions when less than one-quarter full. Bag volume and filling controls may be considered to ensure linen bags are not excessively heavy.


[French scientific contributions to anesthesia. Curares and the neuromuscular junction].
In France, a number of scientists from the fields of chemistry, physiology and surgery have been interested in anaesthesiology. Claude Bernard, who published in 1872 the most exhaustive studies on anaesthesia, was also interested from 1844 in drug curare. He created a methodology, studied pharmacology, including pharmacokinetics and demonstrated the specific action on motor nerves while muscle retained its irritability. It was however A. Vulpian who put forward the idea that curare does not affect the nerve itself but may act on a "linking substance" between nerve and muscle. In these times (1862), Rouget described the end apparatus at the nerve-muscle junction in a way which was finally accepted by German authors. Fifty years later, Couteaux achieved the microanatomic study of the end plate (1909). More recently (1972), Changeux and his team isolated the acetylcholine receptor from the electric organ of the torpedo fish.


Importance of nondiffusive transport for soil CO2 efflux in a temperate mountain grassland.
Soil respiration and its biotic and abiotic drivers have been an important research topic in recent years. While the bulk of these efforts has focused on the emission of CO2 from soils, the production and subsequent transport of CO2 from soil to atmosphere received far less attention. However, to understand processes underlying emissions of CO2 from terrestrial ecosystems, both processes need to be fully evaluated. In this study, we tested to what extent the transport of CO2 in a grassland site in the Austrian Alps could be modeled based on the common assumption that diffusion is the main transport mechanism for trace gases in soils. Therefore, we compared the CO2 efflux calculated from the soil CO2 concentration gradient with the CO2 efflux from chamber measurements. We used four commonly used diffusion-driven models for the flux-gradient approach. Models generally underestimated the soil chamber effluxes and their amplitudes, indicating that processes other than diffusion were responsible for the transport of CO2. We further observed that transport rates correlated well with irradiation and, below a soil moisture content of 33%, with wind speed. This suggests that mechanisms such as bulk soil air transport, due to pressure pumping or thermal expansion of soil air due to local surface heating, considerably influence soil CO2 transport at this site. Our results suggest that nondiffusive transport may be an important mechanism influencing diel and day-to-day dynamics of soil CO2 emissions, leading to a significant mismatch (10-87% depending on the model used) between the two approaches at short time scales.


Antimicrobial effect and shelf-life extension by combined thermal and pulsed electric field treatment of milk.
The impact of a combined hurdle treatment of heat and pulsed electric fields (PEF) was studied on native microbiota used for the inoculation of low-fat ultra-high temperature (UHT) milk and whole raw milk. Microbiological shelf-life of the latter following hurdle treatment or thermal pasteurization was also investigated. UHT milk was preheated to 30 degrees C, 40 degrees C or 50 degrees C over a 60-s period, pulsed for 50 micros or 60 micros at a field strength of 40 kV cm(-1) or for 33 micros at 50 kV cm(-1). Heat and PEF reduced the microbial count by a maximum of 6.4 log in UHT milk (50 degrees C; 50 kV cm(-1), 33 micros) compared to 6.0 log (P > or = 0.05) obtained by thermal pasteurization (26 s, 72 degrees C). When raw milk was treated with a combination of hurdles (50 degrees C; 40 kV cm(-1), 60 micros) a 6.0 log inactivation of microbiota was achieved and microbiological milk shelf-life was extended to 21 days under refrigeration (4 degrees C) vs 14 days in thermally pasteurized milk. Native microbiota was decreased by 6.7 log following conventional pasteurization. The findings suggest that heat and PEF achieved similar inactivation of native microbiota in milk and longer stabilization of microbiological shelf-life than thermal pasteurization. A hurdle approach of heat and PEF could represent a valid milk processing alternative to conventional pasteurization. Hurdle treatment might also preserve native milk quality better due to less thermal exposure.


Suppressed Mobility of Negative Charges in Polymer Electrolytes with an Ether-Functionalized Anion.
Suppressing the mobility of anionic species in polymer electrolytes (PEs) is essential for mitigating the concentration gradient and internal cell polarization, and thereby improving the stability and cycle life of rechargeable alkali metal batteries. Now, an ether-functionalized anion (EFA) is used as a counter-charge in a lithium salt. As the salt component in PEs, it achieves low anionic diffusivity but sufficient Li-ion conductivity. The ethylene oxide unit in EFA endows nanosized self-agglomeration of anions and trapping interactions between the anions and its structurally homologous matrix, poly(ethylene oxide), thus suppressing the mobility of negative charges. In contrast to previous strategies of using anion traps or tethering anions to a polymer/inorganic backbone, this work offers a facile and elegant methodology on accessing selective and efficient Li-ion transport in PEs and related electrolyte materials (for example, composites and hybrid electrolytes).


Web Platform for Gathering and Analyzing Data from the Neurogame Mobile Application.
Today's cell phones are now smartphones, providing a wide range of possibilities for their use, much more than just simple phones. The custom application for the Android operating system, based on an open-source platform for mobile devices is intended for the examination of cognitive functions: attention, concentration and fine motor skills in children of different age groups. The Neurogame application for mobile devices and web platform development is used for retrieving and analyzing mobile application data, providing relevant indicators for the executive functions of the respondents. Material and methods: The research included 50 children with the developmental disorders ADHD and dyslexia (study group) and 50 healthy children (control group), randomly selected, evenly represented by gender and age. Using the application, we determine attention, concentration and motor skills (reaction speed) as part of the executive functions of the respondents. The web platform has the purpose of gathering and processing the data from the mobile application, as well as their automatic visual representation. Results: The ANOVA test showed that there are no gender differences in all the studied groups. A statistical correlation analysis showed that age does not affect the results in healthy school children. In children with dyslexia, age affects positively for total hits and negatively for total misses. In children with ADHD, there is a positive correlation with age for all variables except total hits (t H). Student's T-test showed that there were significant differences for the variables' total hits (t H) and total reaction time (t h) in milliseconds between healthy school children and children with dyslexia. Additionally, Student's t-test indicated that there were significant differences for the variables' total tries (t T) and total hits (t H) between healthy school children and children with ADHD. Finally, Student's t-test indicated that there were significant differences for the variable total tries (t T) between children with dyslexia and children with ADHD. Multiple Regression Results showed a significant difference between healthy school children, children with ADHD and children with dyslexia for all variables (total tries (t T), total hits (t H), total misses (t M) and total reaction time in milliseconds (t h)). Conclusion: The Neurogame application provides a opportunity to assess the motor skills and concentration level, as well as the focus of the target population by measuring the total number of tries, the total number of hits, the total number of misses and the reaction time expressed in milliseconds which are defined as monitoring variables. The development of the web platform and the connection to the application enabled easier access and distribution of the analyzed results to the stakeholders (parents, teachers, therapists or health professionals) in order to further treat the ascertained condition.


X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle.
Stretch activation is important in the mechanical properties of vertebrate cardiac muscle and essential to the flight muscles of most insects. Despite decades of investigation, the underlying molecular mechanism of stretch activation is unknown. We investigated the role of recently observed connections between myosin and troponin, called "troponin bridges," by analyzing real-time X-ray diffraction "movies" from sinusoidally stretch-activated Lethocerus muscles. Observed changes in X-ray reflections arising from myosin heads, actin filaments, troponin, and tropomyosin were consistent with the hypothesis that troponin bridges are the key agent of mechanical signal transduction. The time-resolved sequence of molecular changes suggests a mechanism for stretch activation, in which troponin bridges mechanically tug tropomyosin aside to relieve tropomyosin's steric blocking of myosin-actin binding. This enables subsequent force production, with cross-bridge targeting further enhanced by stretch-induced lattice compression and thick-filament twisting. Similar linkages may operate in other muscle systems, such as mammalian cardiac muscle, where stretch activation is thought to aid in cardiac ejection.


Hypercortisolism due to a Pituitary Adenoma Associated with Beckwith-Wiedemann Syndrome.
Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome with an increased risk of cancer. Most BWS patients show a molecular defect in the 11p15 region that contains imprinted genes. BWS has been associated with malignant neoplasms during infancy. Descriptions of benign tumors, especially in adult patients, are rarer. We report the case of a BWS patient with pituitary adenoma caused by loss of methylation (LOM) at ICR2 (locus CDKN1C/KCNQ1OT1). The patient was referred to an endocrinology unit for suspicion of Cushing's disease due to a history of macroglossia and hemihyperplasia. Biological tests led to the diagnosis of ACTH-dependent hypercortisolism. MRI showed a microadenoma of the pituitary gland, confirming the diagnosis of Cushing's disease. DNA methylation analysis revealed LOM at ICR2 that was in a mosaic state in the patient's leukocytes, but was present in nearly all cells of the pituitary adenoma. The epigenetic defect was associated with a somatic USP8 mutation in the adenoma. Pituitary adenoma rarely occurs in patients with BWS. However, BWS should be considered in cases of pituitary adenoma with minor and/or major signs of BWS. The association between ICR2 LOM and USP8 mutation in the adenoma is questionable. © 2016 S. Karger AG, Basel.


Articulation inspired by nature: a review of biomimetic and biologically active 3D printed scaffolds for cartilage tissue engineering.
In the human body, articular cartilage facilitates the frictionless movement of synovial joints. However, due to its avascular and aneural nature, it has a limited ability to self-repair when damaged due to injury or wear and tear over time. Current surgical treatment options for cartilage defects often lead to the formation of fibrous, non-durable tissue and thus a new solution is required. Nature is the best innovator and so recent advances in the field of tissue engineering have aimed to recreate the microenvironment of native articular cartilage using biomaterial scaffolds. However, the inability to mirror the complexity of native tissue has hindered the clinical translation of many products thus far. Fortunately, the advent of 3D printing has provided a potential solution. 3D printed scaffolds, fabricated using biomimetic biomaterials, can be designed to mimic the complex zonal architecture and composition of articular cartilage. The bioinks used to fabricate these scaffolds can also be further functionalised with cells and/or bioactive factors or gene therapeutics to mirror the cellular composition of the native tissue. Thus, this review investigates how the architecture and composition of native articular cartilage is inspiring the design of biomimetic bioinks for 3D printing of scaffolds for cartilage repair. Subsequently, we discuss how these 3D printed scaffolds can be further functionalised with cells and bioactive factors, as well as looking at future prospects in this field.


Enteritis in cattle due to Yersinia pseudotuberculosis infection.
A selective medium was used to isolate Yersinia sp from the intestinal tract of 222 scouring cattle in Gippsland during 1985 and 1986. Intestinal infection with Y. pseudotuberculosis, particularly of serotype III, was found to be especially prevalent in weaned calves, yearlings and young adult cattle. Clinically affected cattle had a profuse liquid diarrhoea and many were systemically ill. Haematological changes suggestive of infection were present in 38 of 49 of these cattle. At least 35 cattle died and characteristic microabscesses were demonstrated in the intestinal mucosa of 20 of 26 examined histologically. Y. pseudotuberculosis was sensitive to tetracyclines in vitro and this drug produced a rapid bacteriological cure. Yersiniosis occurred during the winter, spring and early summer. Challenge of adult cattle with Y. pseudotuberculosis serotype III did not result in intestinal colonisation or clinical disease. Intestinal infection was, however, established in 4 weaned calves and haematological changes and antibody production were demonstrated in them. Intestinal microabscesses were seen in three calves killed on days 8, 14 and 18 after challenge. The fourth calf eliminated infection by day 18 and no lesions were demonstrated when it was killed on day 72. There is a very high prevalence of antibodies reacting with Y. pseudotuberculosis serotype III in adult cattle. It is concluded that cattle are a common host for this bacterium, infection being frequent, with clinical and fatal disease occurring occasionally. The factors leading to clinical disease are unknown.


Prognostic analysis of different therapeutic regimens in patients with acute cardiogenic cerebral embolism.
Few studies focused on the functional outcomes of patients at 3 months after receiving intravenous thrombolysis, anticoagulation, or antiplatelet therapy within 4.5 h of onset of the cardiogenic cerebral embolism (CCE) subtype. The purpose of this retrospective study was to analyse the clinical data of patients with acute CCE and compare the 3-month functional prognoses of patients after administration of different antithrombotic therapies within 4.5 h of stroke onset. A total of 335 patients with CCE hospitalized in our institution were included in this study. The patients were stratified according to the hyperacute treatment received, and baseline clinical and laboratory data were analysed. A 3-month modified Rankin scale (mRS) score of 0-2 was defined as an excellent functional outcome. A total of 335 patients were divided into thrombolytic (n = 78), anticoagulant (n = 88), and antiplatelet therapy groups (n = 169). A total of 164 patients had a good prognosis at 3 months (mRS ≤ 2). After adjustments were made for age and National Institute of Health Stroke Scale (NIHSS) score, each group comprised 38 patients, and there were no significant differences in sex composition, complications, lesion characteristics, or Oxfordshire Community Stroke Project (OSCP) classification among the three groups. The plasma D-dimer level (µg/ml) in the thrombolytic group was significantly higher than those in the anticoagulant and antiplatelet groups [3.07 (1.50,5.62), 1.33 (0.95,1.89), 1.61 (0.76,2.96), P < 0.001]. After one week of treatment, the reduction in NIHSS in the thrombolytic group was significantly greater than those in the other two groups [3.00 (1.00, 8.00), 1.00 (0.00, 5.00), 1.00 (0.00, 2.00), P = 0.025]. A total of 47 patients (41.2 %) had an mRS score of ≤ 2 at 3 months, and 23 patients died (20.2 %). There was no significant difference in the proportion of patients with a good prognosis or the mortality rate among the three groups (P = 0.363, P = 0.683). Thrombolytic therapy is effective at improving short-term and 3-month prognoses. Anticoagulant therapy may be a safe and effective treatment option for patients with the cardiac stroke subtype who fail to receive intravenous recombinant tissue plasminogen activator (r-tPA) thrombolysis within 4.5 h in addition to antiplatelet therapy, as recommended by the guidelines.


Laparoscopic and endoscopic cooperative surgery for early gastric cancer: Perspective for actual practice.
Early gastric cancer (EGC) has a desirable prognosis compared with advanced gastric cancer (AGC). The surgical concept of EGC has altered from simply emphasizing radical resection to both radical resection and functional preservation. As the mainstream surgical methods for EGC, both endoscopic resection and laparoscopic resection have certain inherent limitations, while the advent of laparoscopic and endoscopic cooperative surgery (LECS) has overcome these limitations to a considerable extent. LECS not only expands the surgical indications for endoscopic resection, but greatly improves the quality of life (QOL) in EGC patients. This minireview elaborates on the research status of LECS for EGC, from the conception and development of LECS, to the tentative application of LECS in animal experiments, then to case reports and retrospective clinical studies. Finally, the challenges and prospects of LECS in the field of EGC are prospected and expounded, hoping to provide some references for relevant researchers. With the in-depth understanding of minimally invasive technology, LECS remains a promising option in the management of EGC. Carrying out more related multicenter prospective clinical researches is the top priority of promoting the development of this field in the future.


Structure and properties of the phosphoenolpyruvate: glucose phosphotransferase system of oral streptococci.
The presence of three distinct enzymes II that catalysed the phosphoenolpyruvate-dependent phosphorylation of glucose, fructose, and mannose was established in membranes of glucose-grown cells of Streptococcus salivarius 25975 and various strains of Streptococcus mutans. The enzyme II mannose phosphorylated mainly mannose, glucose, and 2-deoxyglucose, and the enzyme II glucose phosphorylated glucose, alpha-methylglucoside, and 2-deoxyglucose. The phosphoenolpyruvate-dependent phosphorylation of glucose and alpha-methylglucoside by isolated membrane of wild-type or EII mannose negative mutant cells did not require the presence of any soluble protein other than enzyme I and the phosphocarrier protein HPr. This result suggested that oral streptococci do not possess a soluble factor III glucose. The enzyme II activities varied as a function of the growth sugar but were not coordinately regulated. The variation elicited by specific sugars was not identical for all the strains tested. Nevertheless, in the case of the S. mutans strains, growth at the expense of lactose always caused a significant decrease in the level of enzyme II activities. Finally, experiments conducted with EII mannose negative mutants and also with a pseudorevertant isolated from one of these mutants indicated that the preferential utilization of glucose over lactose by cells growing in mixtures depended on the presence of the EII mannose, but not on glucose-derived metabolites.


Reactive astrocytes in neural repair and protection.
Reactive astrocytosis occurs prominently in response to all forms of CNS injury or disease. The functions of reactive astrocytes are not well understood, and both harmful and beneficial activities have been attributed to these cells. The basic process of reactive astrocytosis is conserved in vertebrate evolution, suggesting fitness-enhancing benefits, but scar-forming reactive astrocytes are often regarded as uniformly detrimental to clinical outcome, in particular, when implicated as inhibitors of axon regeneration. Transgenic mouse models are providing new means to study the activities of reactive astrocytes after CNS insults in vivo. Recent studies point toward roles for reactive astrocytes in restricting inflammation and protecting neurons and oligodendrocytes, thereby helping to limit tissue degeneration and preserve function after CNS injury.


Regulation of striatal dopamine neurotransmission by nitric oxide: effector pathways and signaling mechanisms.
An important role for the reactive gas nitric oxide (NO) in regulating striatal dopaminergic neurotransmission was identified shortly after initial observations indicated that this unorthodox neurotransmitter mediates many of the influences of glutamatergic neurotransmission in the cerebellum, cortex, and hippocampus. While the precise actions of NO on striatal presynaptic and postsynaptic elements remain to be fully characterized, the recent application of sophisticated anatomical, neurochemical, and electrophysiological approaches to the study of nitrergic signaling has revealed that NO exerts a powerful influence both on tonic extracellular dopamine (DA) levels and phasic DA neuron spike activity via the modulation of intrinsic striatal mechanisms and striatonigral feedback loops. Although the nature of the NO-mediated modulatory influence on DA neurotransmission was initially clouded by seemingly conflicting neurochemical observations, a growing body of literature and understanding of the diverse signaling mechanisms and effector pathways utilized by NO indicates that NO exerts a primary facilitatory influence over tonic and phasic dopaminergic neurotransmission under physiological conditions. A review of neurochemical and electrophysiological studies examining the influence of endogenous and exogenous NO on DA neurotransmission indicates that NO signaling exerts multiple effects on local striatal circuits and projection neurons involved in regulating basal ganglia output and nigrostriatal DA neuron activity. In addition to summarizing these influences, the current review focuses on the mechanisms utilized by striatal NO signaling pathways involved in modulating DA transmission at the level of the terminal and cell body and attempts to integrate these observations into a functional model of NO-dependent regulation of basal ganglia systems.


2,2'-Biphosphinines and 2,2'-bipyridines in homoleptic dianionic Group 4 complexes and neutral 2,2'-biphosphinine Group 6 d(6) metal complexes: octahedral versus trigonal-prismatic geometries.
The geometric and electronic structure of formally d(6) tris-biphosphinine [M(bp)(3)](q) and tris-bipyridine [M(bpy)(3)](q) complexes were studied by means of DFT calculations with the B3LYP functional. In agreement with the available experimental data, Group 4 dianionic [M(bp)(3)](2-) complexes (1P-3P for M=Ti, Zr, and Hf, respectively) adopt a trigonal-prismatic (TP) structure, whereas the geometry of their nitrogen analogues [M(bpy)(3)](2-) (1N-3N) is nearly octahedral (OC), although a secondary minimum was found for the TP structures (1N'-3N'). The electronic factors at work in these systems are discussed by means of an MO analysis of the minima, MO correlation diagrams, and thermodynamic cycles connecting the octahedral and trigonal-prismatic limits. In all these complexes, pronounced electron transfer from the metal center to the lowest lying pi* ligand orbitals makes the d(6) electron count purely formal. However, it is shown that the bp and bpy ligands accommodate the release of electron density from the metal in different ways because of a change in the localization of the HOMO, which is a mainly metal-centered orbital in bp complexes and a pure pi* ligand orbital in bpy complexes. The energetic evolution of the HOMO allows a simple rationalization of the progressive change from the TP to the OC structure on successive oxidation of the [Zr(bp)(3)](2-) complex, a trend in agreement with the experimental structure of the monoanionic complex. The geometry of Group 6 neutral complexes [M(bp)(3)] (4P and 5P for M=Mo and W, respectively) is found to be intermediate between the TP and OC limits, as previously shown experimentally for the tungsten complex. The electron transfer from the metal center to the lowest lying pi* ligand orbitals is found to be significantly smaller than for the Group 4 dianionic analogues. The geometrical change between [Zr(bp)(3)](2-) and [W(bp)(3)] is analyzed by means of a thermodynamic cycle and it is shown that a larger ligand-ligand repulsion plays an important role in favoring the distortion of the tungsten complex away from the TP structure.


Switching Protein Localization by Site-Directed RNA Editing under Control of Light.
Site directed RNA editing is an engineered tool for the posttranscriptional manipulation of RNA and proteins. Here, we demonstrate the inclusion of additional N- and C-terminal protein domains in an RNA editing-dependent manner to switch between protein isoforms in mammalian cell culture. By inclusion of localization signals, a switch of the subcellular protein localization was achieved. This included the shift from the cytoplasm to the outer-membrane, which typically is inaccessible at the protein-level. Furthermore, the strategy allows to implement photocaging to achieve spatiotemporal control of isoform switching. The strategy does not require substantial genetic engineering, and might well complement current optogenetic and optochemical approaches.


Sexual Orientation and Gender Identity Reporting in Highly Cited Current Alcohol Research.
Purpose: This study aimed to measure the frequency of high-quality and transparent sexual orientation and gender identity (SOGI) data collection and reporting in highly cited current alcohol use research, using the extant literature to identify community-informed priorities for the measurement of these variables. Methods: A single search to identify alcohol use literature was conducted on PubMed with results restricted to primary research articles published between 2015 and 2022. The 200 most highly cited studies from each year were identified and their titles and abstracts reviewed against inclusion criteria after deduplication. After full-text review, study characteristics and data indicating quality of SOGI reporting were extracted. The fidelity of the results was verified with a random sample before analyses. Results: The final sample comprised 580 records. Few studies reported gender identity (n = 194; 33.4%) and, of these, 7.2% reported the associated gender identity measure. A two-stage approach to measure gender was adopted in 3 studies, one study used an open-ended question with a free-text response option, and 13 studies recorded nonbinary gender identities (reported by 0.9% of the whole sample). Nineteen (3.3%) studies reported sexual orientation and more than half of these provided the sexual orientation measure. Eight of the 20 studies that reported sexual orientation and/or gender identity measures were classified as sexual and gender minority specialist research. Conclusions: Culturally competent SOGI reporting is lacking in highly cited current alcohol research. SOGI measures should be disclosed in future research and should provide free-text response options.


Diminishing Interfacial Turbulence by Colloid-Polymer Electrolyte to Stabilize Zinc Ion Flux for Deep-Cycling Zn Metal Batteries.
The fluidity of aqueous electrolytes and undesired H2 evolution reaction (HER) can cause severe interfacial turbulence in aqueous Zn metal batteries (ZMBs) at deep cycling with high capacities and current densities, which would further perturb ion flux and aggravate Zn dendrite growth. In this study, a colloid-polymer electrolyte (CPE) with special colloidal phase and suppressed HER is designed to diminish interfacial turbulence and boost deep Zn electrochemistry. Density functional theory calculations confirm that the quantitative migratory barriers of Zn2+ along the transport pathway in CPE demonstrate much smaller fluctuations compared with normal aqueous electrolyte, indicating that CPE can effectively diminish interfacial disturbance. Benefitting from this, the Zn2+ ion flux can be homogenized and deposited evenly on the electrode, which is confirmed by finite element simulation and in situ Raman measurements. Consequently, CPE enables stable operation of Zn//Cu cells even with high capacity (up to 20 mAh cm-2 ) and current density (up to 100 mA cm-2 ) and Zn//Na5 V12 O32 full-cell with N/P ratio as low as 1 (i.e., 100% Zn utilization). It is believed that this strategy opens a brand-new avenue based on CPE toward boosting deep-cycling electrochemistry in ZMBs and even other aqueous energy-storage applications.


Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with Leber hereditary optic neuropathy.
Leber hereditary optic neuropathy (LHON) is a maternally inherited eye disease most commonly caused by mitochondrial DNA (mtDNA) point mutation at position 11778, 3460, or 14484. Approximately 14% of families show heteroplasmy for the pathogenic mutations but little is known about the mutational burden in different tissues of these heteroplasmic individuals. Consequently, estimating the risks of visual loss is difficult. This study presents quantitative mutation analyses of tissues representing all embryonal layers in two families heteroplasmic for the 11778 mutation. These analyses show that a high amount of mutated mtDNA in leukocytes is correlated with a high proportion of mutated mtDNA in other tissues.


Long-Acting Antiretrovirals: Where Are We now?
Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.


Adverse effects of chronic opioid therapy for chronic musculoskeletal pain.
The use of opioids for the treatment of chronic pain has increased dramatically over the past decade. Whether these drugs provide considerable benefits in terms of pain reduction and improved function to balance the risks associated with their use, however, is unclear. Of particular importance to clinicians treating chronic musculoskeletal pain is opioid-induced hyperalgesia, the activation of pronociceptive pathways by exogenous opioids that results in central sensitization to pain. This phenomenon results in an increase in pain sensitivity and can potentially exacerbate pre-existing pain. Opioids also have powerful positive effects on the reward and reinforcing circuits of the brain that might lead to continued drug use, even if there is no abuse or misuse. The societal risk of increased opioid prescription is associated with increased nonmedical use, serious adverse events and death. Patients with chronic musculoskeletal pain should avoid the long-term use of opioids unless the benefits are determined to outweigh risks, in which case, the use of chronic opioids should be regularly re-evaluated.


A comparison of gemeprost (Cervagem) pessaries and Lamicel tents for cervical preparation for abortion by dilatation and suction.
In a randomized, single-blind trial, 78 women having vaginal termination of pregnancy were treated with either a 1-mg gemeprost (Cervagem) pessary or a Lamicel tent inserted 3-4 h before operation. Both agents produced satisfactory cervical softening but dilatation was significantly easier after gemeprost. Pre-operative side-effects were more frequent after gemeprost but did not increase the need for analgesia. There were no differences between the two groups with regard to either postoperative symptoms and analgesic requirements or pre-operative and postoperative temperature, pulse rate and blood pressure. Gemeprost pessaries are easier, faster and less uncomfortable to administer.


Fixational eye movement: a negligible source of dynamic aberration.
To evaluate the contribution of fixational eye movements to dynamic aberration, 50 healthy eyes were examined with an original custom-built Shack-Hartmann aberrometer, running at a temporal frequency of 236Hz, with 22 lenslets across a 5mm pupil, synchronized with a 236Hz pupil tracker. A comparison of the dynamic behavior of the first 21 Zernike modes (starting from defocus) with and without digital pupil stabilization, on a 3.4s sequence between blinks, showed that the contribution of fixational eye movements to dynamic aberration is negligible. Therefore we highlighted the fact that a pupil tracker coupled to an Adaptive Optics Ophthalmoscope is not essential to achieve diffraction-limited resolution.


Clinical Effects of Subgingivally Delivered Achyranthes Aspera Gel in Chronic Periodontitis: A Clinical and Microbiological Study.
Periodontitis is an inflammatory disease of microbial origin. Local drug delivery agents help reduce subgingival microflora. Achyranthes aspera is a medicinal herb with antimicrobial, antioxidant, anti-inflammatory, and wound-healing properties. A split-mouth study was conducted, in which 60 sites were included. Clinical parameters included measurements of probing depth (PD), gingival index, and clinical attachment level (CAL). Gingival crevicular fluid (GCF) samples were collected, followed by microbiological analysis of Porphyromonas Gingivalis. Clinical and microbiological parameters were recorded at baseline and after 3 months. Statistical analysis was done using the Statistical Package of Social Science (SPSS Version 22; Chicago Inc., USA). At 3 months, Group A resulted in greater mean reductions in clinical parameters: PD (3.77) as compared to Group B (5.23), and also greater mean CAL gain (3.18) in group A as compared to Group B (5.16). Group A also showed a significant reduction in the number of sites harboring periodontopathogens as compared to Group B. A. aspera gel can be used as a nonsurgical local drug delivery agent in patients with chronic periodontitis as an effective adjunct to SRP.


Transforming Growth Factor β Acts as a Regulatory Molecule for Lipogenic Pathways among Hepatitis C Virus Genotype-Specific Infections.
Hepatitis C virus (HCV) infection promotes metabolic disorders, and the severity of lipogenic disease depends upon the infecting virus genotype. Here, we have examined HCV genotype 1-, 2-, or 3-specific regulation of lipid metabolism, involving transforming growth factor β (TGF-β)-regulated phospho-Akt (p-Akt) and peroxisome proliferator-activated receptor alpha (PPARα) axes. Since HCV core protein is one of the key players in metabolic regulation, we also examined its contribution in lipid metabolic pathways. The expression of regulatory molecules, TGF-β1/2, phospho-Akt (Ser473), PPARα, sterol regulatory element-binding protein 1 (SREBP-1), fatty acid synthase (FASN), hormone-sensitive lipase (HSL), and acyl dehydrogenases was analyzed in virus-infected hepatocytes. Interestingly, HCV genotype 3a exhibited much higher activation of TGF-β and p-Akt, with a concurrent decrease in PPARα expression and fatty acid oxidation. A significant and similar decrease in HSL, unlike in HCV genotype 1a, was observed with both genotypes 2a and 3a. Similar observations were made from ectopic expression of the core genomic region from each genotype. The key role of TGF-β was further verified using specific small interfering RNA (siRNA). Together, our results highlight a significant difference in TGF-β-induced activity for the HCV genotype 2a- or 3a-induced lipogenic pathway, exhibiting higher triglyceride synthesis and a decreased lipolytic mechanism. These results may help in therapeutic modalities for early treatment of HCV genotype-associated lipid metabolic disorders.IMPORTANCE Hepatic steatosis is a frequent complication associated with chronic hepatitis C virus (HCV) infection and is a key prognostic indicator for progression to fibrosis and cirrhosis. Several mechanisms are proposed for the development of steatosis, especially with HCV genotype 3a. Our observations suggest that transforming growth factor β (TGF-β) and peroxisome proliferator-activated receptor alpha (PPARα)-associated mechanistic pathways in hepatocytes infected with HCV genotype 2a and 3a differ from those in cells infected with genotype 1a. The results suggest that a targeted therapeutic approach for enhanced PPARα and lipolysis may reduce HCV genotype-associated lipid metabolic disorder in liver disease.


Phosphatidylinositol 3,4,5-Trisphosphate Phosphatase SKIP Links Endoplasmic Reticulum Stress in Skeletal Muscle to Insulin Resistance.
Insulin resistance is critical in the pathogenesis of type 2 diabetes. Endoplasmic reticulum (ER) stress in liver and adipose tissues plays an important role in the development of insulin resistance. Although skeletal muscle is a primary site for insulin-dependent glucose disposal, it is unclear if ER stress in those tissues contributes to insulin resistance. In this study, we show that skeletal muscle kidney-enriched inositol polyphosphate phosphatase (SKIP), a PIP3 (phosphatidylinositol-3,4,5-trisphosphate) phosphatase, links ER stress to insulin resistance in skeletal muscle. SKIP expression was increased due to ER stress and was higher in the skeletal muscle isolated from high-fat-diet-fed mice and db/db mice than in that from wild-type mice. Mechanistically, ER stress promotes activating transcription factor 6 (ATF6) and X-box binding protein 1 (XBP1)-dependent expression of SKIP. These findings underscore the specific and prominent role of SKIP in the development of insulin resistance in skeletal muscle.


Pediatric Tui Na for Feeding Intolerance in Premature Infants: Protocol for a Systematic Review and Meta-Analysis.
Feeding intolerance (FI), frequently resulting from gastrointestinal immaturity, is prevalent among premature infants. Current practices are gradually prioritizing nonpharmacological treatments, such as massage or "Tui na," considering the potential side effects of prolonged medication use. Pediatric Tui na, a specialized massage therapy based on traditional Chinese medicine, has been widely studied for treating FI in premature infants. However, to our knowledge, no systematic review specifically focusing on the effectiveness and safety of traditional Chinese medicine-based pediatric Tui na for FI in premature infants has been published yet. This study aims to develop a protocol for a systematic review and meta-analysis for evaluating the safety and efficacy of pediatric Tui na for premature infants with FI. We will perform a comprehensive search in the following databases: Springer, Cochrane Library, Embase, MEDLINE, Clarivate Analytics, Physiotherapy Evidence Database (PEDro), CINAHL, PubMed, Scopus, World Health Organization (WHO) International Clinical Trials Registry Platform, and Chinese biomedical databases (Wanfang database, the China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Chinese Biomedical Literature Databases), limited to studies published in Chinese and English languages between January 2000 and January 2023. The search strategy will use MeSH (Medical Subject Headings) terms and database-specific keywords. A total of 2 independent reviewers will initially screen the studies based on titles and abstracts, followed by a full-text evaluation of the eligible studies. Studies will include any nonrandomized controlled trials, nonrandomized clinical studies, randomized controlled trials, and quasi-experimental studies wherein the treatment group involves premature infants with FI given pediatric Tui na. Primary outcomes will be necrotizing enterocolitis, gastric residual volume, emesis, and stool blood. Secondary outcomes will be abdominal distension weight gain, time to achieve full enteral feeding, any adverse effects associated with pediatric Tui na, and length of hospital stay. The Cochrane Collaboration Risk of Bias Tool will be used to assess the risk of bias and methodological quality. Funnel plots will be used for evaluating publication bias. Meta-analysis will be conducted using the Review Manager software (version 5.4; Cochrane Collaboration). Subgroup analyses will be considered according to treatment received, country or setting, sex, and birth weight of premature infants (if heterogeneity is high, I2≥50%). This is a systematic review and meta-analysis protocol, so the results are not yet available. The protocol has been registered with PROSPERO (CRD42023390021). We are currently in the study selection phase. Results are expected to be completed by the end of 2023. Following this protocol, a comprehensive and rigorous literature synthesis will be developed to assess the impact of pediatric Tui na treatment on premature infants with FI, enabling the determination of its efficacy and safety. PROSPERO CRD42023390021; https://tinyurl.com/bdf4kn23. PRR1-10.2196/46375.


Monitoring fetal growth in settings with limited ultrasound access.
Abnormal fetal growth significantly increases neonatal mortality and the risk of stillbirth. This creates the need for accurately monitoring fetal growth in all pregnancies regardless of the risk status. Several methods used in clinical practice include abdominal palpation, symphysio-fundal height measurements, and obstetric ultrasound. Of these, obstetric ultrasound remains the most reliable and objective way to monitor fetal growth. However, in most low-resource areas, access to obstetric ultrasound remains poor and this leaves the two as the only options available. This not only has effect on fetal growth monitoring but more importantly on the accuracy of pregnancy dating. To improve the current situation, we propose strategies for training of health workers, educating the public on importance of obstetric ultrasound, and improving access to basic equipment. However, interim solutions have to be implemented hand in hand with other strategies to ensure universal access to ultrasound technology for fetal growth monitoring.


A 22-kd protein (sorcin/V19) encoded by an amplified gene in multidrug-resistant cells, is homologous to the calcium-binding light chain of calpain.
We have previously shown that at least five linked genes are co-amplified and overexpressed in the multi-drug resistant (MDR) Chinese hamster ovary cell line CHRC5. We show here that one of these genes (class 4) codes for a small phosphorylated, cytosolic protein, sorcin/V19, known to be overproduced by many MDR cell lines. The class 4 gene codes for a nested set of mRNAs, varying in size between 1000 and 2500 nucleotides. Sequence analysis of complementary DNAs shows that these mRNAs encode a protein of 198 amino acids. The identity of this protein with sorcin was established by comparison with the amino acid sequence of two peptides from mouse sorcin. Hamster sorcin is a 22-kd protein with four 'E-F hand' structures typical of calcium-binding sites and it has substantial homology with the light chain of calpain. Two of the calcium-binding sites contain putative recognition sites for cAMP-dependent protein kinase. These may account for the known phosphorylation of sorcin. The unknown function of sorcin might therefore be controlled by both calcium and cAMP levels. The contribution of sorcin to multidrug resistance, if any, remains to be tested.


Utilizing the Discrete Element Method for the Modeling of Viscosity in Concentrated Suspensions.
The rheological behavior of concentrated suspensions is a complicated problem because it originates in the collective motion of particles and their interaction with the surrounding fluid. For this reason, it is difficult to accurately model the effect of various system parameters on the viscosity even for highly simplified systems. We model the viscosity of a hard-sphere suspension subjected to high shear rates using the dynamic discrete element method (DEM) in three spatial dimensions. The contact interaction between particles was described by the Hertz model of elastic spheres (soft-sphere model), and the interaction of particles with flow was accounted for by the two-way coupling approach. The hydrodynamic interaction between particles was described by the lubrication theory accounting for the slip on particle surfaces. The viscosity in a simple-shear model was evaluated from the force balance on the wall. The obtained results are in close agreement with literature data for systems with hard spheres. Namely, the viscosity is shown to be independent of shear rate and primary particle size for monodisperse suspensions. In accordance with theory and experimental data, the viscosity grows rapidly with particle volume fraction. We show that this rheological behavior is predominantly caused by the lubrication forces. A novel approach based on the slip of water on a particle surface was developed to overcome the divergent behavior of lubrication forces. This approach was qualitatively validated with literature data from AFM measurements using a colloidal probe. The model presented in this work represents a new, robust, and versatile approach to the modeling of viscosity in suspensions with the possibility to include various interaction models and study their effect on viscosity.


Three-dimensional models for beta-adrenergic receptor complexes with agonists and antagonists.
Molecular modeling methods have been used to construct three-dimensional models for agonist and antagonist complexes with beta-adrenergic receptors. The recent rhodopsin crystal structure was used as a template in standard homology modeling methods. The rhodopsin-based homology models were assessed for agreement with experimental results for beta-adrenergic receptors, and compared with receptor models developed using de novo modeling techniques. While the de novo and homology-derived receptor models are generally quite similar, there are some localized structural differences that impact the putative ligand-binding site significantly. The de novo receptor models appear to provide much better agreement with experimental data, particularly for receptor complexes with agonist ligands. The de novo receptor models also yield some interesting and testable hypotheses for the structural basis of beta-adrenergic receptor subtype ligand selectivity.


The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium "The Intelligent Intestine," held in Paris, June 14, 2002.
The intestine is an extremely complex living system that participates in the protection of the host through a strong defense against aggressions from the external environment. This defensive task is based on 3 constituents that are in permanent contact and dialog with each other: the microflora, mucosal barrier, and local immune system. We review herein current knowledge about these important functions. The gut microflora play a major role against exogenous bacteria through colonization resistance, but the mechanism of action is not yet established, although it is linked to the bacteria colonizing the gut. This colonization involves bacteria-bacteria dialog, bacteria-mucins interactions, and bacteria-colonocytes cross-talk associated with environmental factors. The intestinal mucosa is a cellular barrier and the main site of interaction with foreign substances and exogenous microorganisms. It is a complex physicochemical structure consisting of a mucous layer linked to cellular and stromal components that participate in the defense of the host through mucosal blood flow, mucosal secretions, epithelial cell functionals, surface hydrophobicity, and defensin production. The intestine is the primary immune organ of the body represented by the gut-associated lymphoid tissue through innate and acquired immunity. This immune system can tolerate dietary antigens and the gut-colonizing bacteria and recognizes and rejects enteropathogenic microorganisms that may challenge the body's defenses. In cooperation with these endogenous barriers, some in-transit bacteria, such as probiotics, can act as partners of the defense system of the intestine.


The oncogene Nup98-HOXA9 induces gene transcription in myeloid cells.
The nucleoporin Nup98 gene is frequently rearranged in acute myelogenous leukemia (AML). In most cases this results in fusion of the N terminus of Nup98 to the DNA binding domain of a homeodomain transcription factor. The prototype of these fusions, Nup98-HOXA9, is associated with human AML and induces AML in mouse models. To understand the mechanisms by which Nup98-HOXA9 causes AML, we expressed it in myeloid cells and identified its target genes using high density oligonucleotide microarrays. The analysis was performed in triplicate and was confirmed by quantitative real time PCR. Of the 102 Nup98-HOXA9 target genes identified, 92 were up-regulated, and only 10 were down-regulated, suggesting a transcriptional activation function. A similar analysis of wild-type HOXA9 revealed 13 target genes, 12 of which were up-regulated, and 1 was down-regulated. In contrast, wild-type Nup98 had no effect on gene expression, demonstrating that the HOXA9 DNA binding domain is required for gene regulation. Co-transfection experiments using a luciferase reporter linked to the promoter of one of the Nup98-HOXA9 target genes confirmed up-regulation at the transcriptional level by Nup98-HOXA9 but not by either HOXA9 or Nup98. These data indicate that Nup98-HOXA9 is an aberrant transcription factor whose activity depends on the HOXA9 DNA binding domain but has a stronger and wider transcriptional effect than HOXA9. Several of the genes regulated by Nup98-HOXA9 are associated with increased cell proliferation and survival as well as drug metabolism, providing insights into the pathogenesis and epidemiology of Nup98-HOXA9-induced AML.


cDNA cloning, expression and homology modeling of a luciferase from the firefly Lampyroidea maculata.
The cDNA of a firefly luciferase from lantern mRNA of Lampyroidea maculata has been cloned, sequenced and functionally expressed. The cDNA has an open reading frame of 1647 bp and codes for a 548-residue-long polypeptide. Noteworthy, sequence comparison as well as homology modeling showed the highest degree of similarity with H. unmunsana and L. mingrelica luciferases, suggesting a close phylogenetic relationship despite the geographical distance separation. The deduced amino acid sequence of the luciferase gene of firefly L. maculata showed 93% identity to H. unmunsana. Superposition of the three-dimensional model of L. maculata luciferase (generated by homology modeling) and three dimensional structure of Photinus pyralis luciferase revealed that the spatial arrangements of Luciferin and ATP-binding residues are very similar. Putative signature of AMPbinding domain among the various firefly species and Lampyroidea maculata was compared and a striking similarity was found. Different motifs and sites have been identified in Lampyroidea maculata by sequence analysis. Expression and purification of luciferase from Lampyroidea maculata was carried out using Ni-NTA Sepharose. Bioluminescence emission spectrum was similar to Photinus pyralis luciferase.


[Dependency of heart rate on contrast medium temperature and coronary angiographic severity in coronary angiography].
The influence of temperature (24 degrees C, 34 degrees C) of contrast medium (Urografin 76) on sinus frequency was studied during diagnostic coronary arteriographies in patients with different degree of coronary heart disease. 1. Injection of contrast medium in both coronary arteries was associated with a decrease of heart rate by 4.1-12.8%. There was no significant difference between the decrease in heart rate when injecting the contrast medium into the right or into the left coronary artery. 2. The change in heart rate during left and right coronary arteriography was independent from the temperature of the contrast medium (24 degrees C, 34 degrees C). Therefore, coronary arteriography made at 25 degrees C does not produce significant changes in heart rate when compared to coronary arteriography performed with contrast medium which has been warmed by 10 degrees C (34 degrees C). 3. Heart rate was decreased parallel to the increase in severity of coronary artery stenosis. The possible underlying mechanisms (changes in coronary artery perfusion pressure, hypoxic bradycardia) are being discussed.


When Nordic neurosurgery was still in its infancy.
Olof af Acrel, the father of Swedish Surgery, operated in 1768 upon a young nobleman who had experienced an increasing swelling on the skull, due to a tumour which also turned out to be growing deep into the brain parenchyma. The patient survived the operation for 3 days. Edvard Bull in 1877, after diagnosing a ruptured internal carotid artery aneurysm in a young female who temporarily recovered after her first hemorrhage, emphasised that the risk of a second, fatal haemorrhage--which in fact occurred--was immediate. He predicted that carotid ligation might be a way to reduce the risk of repeated haemorrhage from such aneurysms. Virtually unknown to modern neurosurgeons are many remarkable Nordic pioneers who, in the 1800's and early 1900's, rendered major contributions to the birth of modern neurological surgery. Thus early neurosurgical operations were performed by Carl Daniel von Haartman in Finland and by Christopher Withusen and Gundelach Møller in Denmark. von Haartman and Withusen had both visited Sir Astley Cooper in London in 1816. Vilhelm Magnus of Oslo was a neurosurgical giant, who had been trained by Victor Horsley during visits to London in 1903 and 1904. Magnus performed his first two-stage operation for a tumour located deep in the left cerebral hemisphere in 1903. By 1921, he had operated upon 112 cases of intracranial tumour with an 8.1% surgical mortality. His results were certainly fully comparable with those of his contemporary American pioneer--Harvey Cushing. Vilhelm Magnus, who worked alone under primitive conditions in small private hospitals, published altogether 70 scientific papers. In 1925 his series comprised 189 patients operated upon for brain tumours with 7.7% surgical mortality in supratentorial, and 17.8% mortality in infratentorial tumours. Magnus was congratulated on his brilliant achievements by a Swedish colleague 20 years his junior, Herbert Olivecrona, the man who was to carry on his pioneering work in Sweden.


Human mucus proteinase inhibitor (human MPI). Human seminal inhibitor I (HUSI-I), antileukoprotease (ALP), secretory leukocyte protease inhibitor (SLPI).
Human mucous secretions contain a proteinase inhibitor which is produced locally and inhibits, besides trypsin and chymotrypsin, granulocytic elastase and cathepsin G as well as mast cell chymase and tryptase. The various inhibitors isolated from different sources (bronchial mucus, parotid secretion, seminal plasma, cervical mucus, etc.) and named accordingly (bronchial mucus inhibitor, BMI; human seminal inhibitor I, HUSI-I; cervical mucus inhibitors, CUSI; antileukoprotease, ALP; secretory leukocyte protease inhibitor, SLPI) proved to be identical or derived from a mature inhibitory protein encoded by a single gene of the human genom. Therefore, this inhibitor should be named mucus proteinase inhibitor, MPI. Such a neutral terminus would help to avoid misleading interpretations of already published data and also of the biological role of this inhibitory protein because the MPI may serve several and different physiological functions.


New approach for spinal cord stimulation trial.
Spinal cord stimulation trial phase has remained unchanged for years. The common practice to connect a lead to an external transmitter is not optimal. The operational mode of transmitter is different from implanted system and external bulky device interferes with patient's daily routine. Optimization in the trial period may increase patient's satisfaction and improve outcome of upcoming permanent implantation. The proposed new trial design can be a simple and logical solution of the problem.


Isolation and characterization of Yersinia enterocolitica from swine feces recovered during the National Animal Health Monitoring System Swine 2000 study.
A national study was conducted for the isolation of pathogenic Yersinia enterocolitica in pig feces in the United States as part of the National Animal Health Monitoring System's Swine 2000 study. Fecal samples collected from swine operations from September 2000 to March 2001 from 77 production sites in 15 of the top 17 swine-producing states were tested for the presence of pathogenic Y. enterocolitica. After enrichment of swine fecal samples in irgasan-ticarcillin-potassium chlorate broth, the enriched cultures were plated on cefsulodin-irgasan-novobiocin agar for isolation of presumptive Y. enterocolitica. The isolates were confirmed as pathogenic Y. enterocolitica by the fluorogenic 5' nuclease PCR assay targeting the chromosomal attachment invasion ail gene. Of 2793 fecal samples tested, 106 (3.80%) ail-positive strains of Y. enterocolitica were isolated. These 106 ail-positive isolates originated from 7 of the 15 participating states. The predominant serotype O:3 (n = 79 of 106) was distributed in five states (n = 5 of 7). Serotype O:5 (n = 27 of 106) was also found in five states (n = 5 of 7). All isolates contained the virulence plasmid and expressed virulence-associated phenotypic characteristics. These results indicate that swine in the United Stares harbor Y. enterocolitica that can potentially cause human illness.


Downregulation of microRNA-138 enhances the proliferation, migration and invasion of cholangiocarcinoma cells through the upregulation of RhoC/p-ERK/MMP-2/MMP-9.
microRNAs (miRs) play an important role in tumor initiation and progression in many types of cancer, including cholangiocarcinoma (CC). miR-138 dysregulation is frequently observed in a variety of tumors. In the present study, miR-138 was found to be downregulated in CC tissues by quantitative real-time RT-PCR. Furthermore, its potential target molecule, Ras homolog gene family, member C (RhoC) protein, was found to be highly expressed in CC tissues examined by western blot analysis. Luciferase reporter assay further demonstrated that miR-138 directly targeted RhoC. We found that the introduction of miR-138 mimics to RBE and QBC939 CC cells could reduced RhoC mRNA and protein expression, and suppressed the proliferation, G1/S transition, migration and invasion of CC cells. However, transfection with a miR-138 inhibitor induced an inverse effect in CC cells. The expression of phosphorylated extracellular signal-regulated kinase (p-ERK), matrix metalloproteinase (MMP)-2 and MMP-9 decreased following transfection with miR-138, and increased following transfection with miR-138 inhibitor in CC cells. In conclusion, RhoC upregulation induced by miR-138 downregulation promotes the malignant progression of CC cells and the underlying mechanisms of this effect involve the increase in the expression of p-ERK/MMP-2/MMP-9. Consequently, miR-138/RhoC is a potential target for the clinical diagnosis and treatment of CC.


Acute neurological events associated with influenza vaccination: are the WHO criteria for assessing causality adequate?
We identified neurological admissions temporally associated with influenza vaccine to determine the likelihood of causality using World Health Organization (WHO) criteria. Although all cases were categorized as possibly related to the vaccine, most had a compelling alternative explanation. This observation suggests that the current WHO criteria may not be sufficient in determining if an adverse event is truly vaccine related.


Acute renal failure caused by nontraumatic rhabdomyolysis.
Nontraumatic rhabdomyolysis may be associated with severe metabolic disturbances. In particular, previous literature has described a 8-20% incidence of acute renal failure in rhabdomyolysis. The aim of this study was to evaluate our experience on 11 patients with acute renal failure treated by high-efficiency daily hemodialysis.


Application of Fused Reality Holographic Image and Navigation Technology in the Puncture Treatment of Hypertensive Intracerebral Hemorrhage.
Minimally invasive puncture and drainage (MIPD) of hematomas was the preferred option for appropriate patients with hypertensive intracerebral hemorrhage (HICH). The goal of our research was to introduce the MIPD surgery using mixed reality holographic navigation technology (MRHNT). We provided the complete workflow for hematoma puncture using MRHNT included three-dimensional model reconstruction by preoperative CT examination, puncture trajectory design, immersive presentation of model, and real environment and hematoma puncture using dual-plane navigation by wearing special equipment. We collected clinical data on eight patients with HICH who underwent MIPD using MRHNT from March 2021 to August 2021, including the hematoma evacuation rate, operation time, deviation in drainage tube target, postoperative complications, and 2-week postoperative GCS. The workflow for hematoma puncture using MRHNT were performed in all eight cases, in which the average hematoma evacuation rate was 47.36±9.16%, the average operation time was 82.14±15.74 min, and the average deviation of the drainage tube target was 5.76±0.80 mm. There was no delayed bleeding, acute ischemic stroke, intracranial infection, or epilepsy 2 weeks after surgery. The 2-week postoperative GCS was improved compared with the preoperative GCS. The research concluded it was feasible to perform the MIPD by MRHNT on patients with HICH. The risk of general anesthesia and highly professional holographic information processing restricted the promotion of the technology, it was necessary for technical innovation and the accumulation of more case experience and verification of its superiority.


Probing Retroviral and Retrotransposon Genome Structures: The "SHAPE" of Things to Come.
Understanding the nuances of RNA structure as they pertain to biological function remains a formidable challenge for retrovirus research and development of RNA-based therapeutics, an area of particular importance with respect to combating HIV infection. Although a variety of chemical and enzymatic RNA probing techniques have been successfully employed for more than 30 years, they primarily interrogate small (100-500 nt) RNAs that have been removed from their biological context, potentially eliminating long-range tertiary interactions (such as kissing loops and pseudoknots) that may play a critical regulatory role. Selective 2' hydroxyl acylation analyzed by primer extension (SHAPE), pioneered recently by Merino and colleagues, represents a facile, user-friendly technology capable of interrogating RNA structure with a single reagent and, combined with automated capillary electrophoresis, can analyze an entire 10,000-nucleotide RNA genome in a matter of weeks. Despite these obvious advantages, SHAPE essentially provides a nucleotide "connectivity map," conversion of which into a 3-D structure requires a variety of complementary approaches. This paper summarizes contributions from SHAPE towards our understanding of the structure of retroviral genomes, modifications to which technology that have been developed to address some of its limitations, and future challenges.


Bariatric Space, Technology, and Design: A Round Table.
Planning and executing healthcare for the patient or resident living with obesity can be a challenging task that has implications to the occupational health professional. Leading global experts in the areas of occupational health, ergonomics, bariatrics, technology, and patient care were identified and invited to participate in a round table discussion. Questions posed to experts were based on literature that addressed patient handling and mobility, architectural design recommendations, clinical care of the person with obesity, and ergonomic guidelines. Experts agreed that special considerations must be in place to care for the person who is obese. These special considerations should address not only clinical care of the patient, but ways to protect workers from occupational injury associated with clinical care. Experts suggested that, in some situations, a bariatric training suit may be helpful in better understanding space and design challenges, as well as a better understanding of the physical limitations associated with a larger body habitus (although simulated). Further, experts agreed that insensitivities often stem from failure to have proper space, technology and design accommodations in place. Conclusions/Application to Practice: The occupational health professional is a key resource to teams charged with planning and executing healthcare for the patient or resident living with obesity. Interprofessional understanding and communication can lead to a more comprehensive approach to space, design and technology that not only addresses the patient, but the worker providing direct care.


Can CD200R1 Agonists Slow the Progression of Osteoarthritis Secondary to Injury?
Post-traumatic knee osteoarthritis is characterized by cartilage degeneration, subchondral bone remodeling, osteophyte formation, and synovial changes. Therapeutic targeting of inflammatory activity in the knee immediately post injury may alter the course of osteoarthritis development. This study aimed to determine whether CD200R1 agonists, namely the protein therapeutic CD200Fc or the synthetic DNA aptamer CCS13, both known to act as anti-inflammatory agents, are able to delay the pathogenesis of injury-associated knee osteoarthritis in a murine model. Ten week old male C57BL/6 mice were randomized and surgical destabilization of the medial meniscus (DMM) to induce knee arthritis or sham surgery as a control were performed. CCS13 was evaluated as a therapeutic treatment along with CD200Fc and a phosphate-buffered saline vehicle control. Oligonucleotides were injected intra-articularly beginning one week after surgery, with a total of six injections administered prior to sacrifice at 12 weeks post-surgery. Histopathological assessment was used as the primary outcome measure to assess cartilage and synovial changes, while µCT imaging was used to compare the changes to the subchondral bone between untreated and treated arthritic groups. We did not find any attenuation of cartilage degeneration or synovitis in DMM mice with CD200Fc or CCS13 at 12 weeks post-surgery, nor stereological differences in the properties of subchondral bone. The use of CD200R1 agonists to blunt the inflammatory response in the knee are insufficient to prevent disease progression in the mouse DMM model of OA without anatomical restoration of the normal joint biomechanics.


CONTRASTING CONCURRENT AND CHILDHOOD SOCIOECONOMIC PREDICTORS OF SELF-RATED HEALTH AMONG OLDER EUROPEAN MEN AND WOMEN.
This study aimed to assess the relative importance of childhood and adulthood socioeconomic position (SEP) on the self-rated health (SRH) of men and women aged 50 or higher in Europe, controlling for a substantial number of mediators and health conditions. Data from Wave 2 (current data) and Wave 3 (retrospective material) of the Survey of Health, Ageing and Retirement in Europe (SHARE) were combined (N=20,829) and logistic regression models applied; the analysis was carried out for males and females separately. The findings indicate that concurrent and past SEP, when considered separately, are both very significant predictors of SRH. When all factors were included in a comprehensive model most childhood and adult SEP variables retained their significance, implying that both types of socioeconomic circumstances have a strong and independent effect on SRH. However, the relative importance of several childhood indicators was reduced, signifying that their effect on SRH is mediated by adult SEP and, especially, educational attainment. Some childhood predictors, such as having experienced a period of hunger, remained very significant. Though these findings roughly hold for both sexes, the relative effects differentiate by sex. Current SEP is more important among women, with the exception of income and 'making ends meet in the household'. Childhood SEP indicators are more significant among men.


Analysis of personal care products on model skin surfaces using DESI and PADI ambient mass spectrometry.
Two ambient ionisation techniques, desorption electrospray ionisation (DESI) and plasma assisted desorption ionisation (PADI), have been used to analyse personal care products (PCPs) on fixed fibroblast cell surfaces. The similarities and differences between the two techniques for this type of analysis have been explored in various ways. Here, we show the results of DESI and PADI analysis of individual PCP ingredients as well as the analysis of these as complex creams on model skin surfaces, with minimal sample preparation. Typically, organosiloxanes and small molecules were detected from the creams. A study of the morphological damage of the fibroblast cells by the two ionisation techniques showed that for a less than 10% reduction in cell number, acquisition times should be limited to 5 s for PADI, which gives good signal levels; with DESI, the morphological damage was negligible. The operating parameters for the plasma source were optimised, and it was also found that the parameters could be modified to vary the relative intensity of different ions in the mass spectrum.


Collagen characteristics affect the texture of pork Longissimus and Biceps femoris.
Connective tissue is considered to influence the toughness of pork, but most studies on connective tissue focus on the loin muscle. Cooking loss, Warner-Bratzler shear force (WBSF), texture profile analysis (hardness, springiness, chewiness, resilience, and cohesiveness), total and insoluble collagen content, the percentage of type III collagen relative to the total of type I and III collagen, proteoglycan content and intramuscular fat (IMF) content were measured for pork Biceps femoris (BF) and Longissimus thoracis et lumborum (LTL) and Pearson's correlation was performed. The results showed that BF had higher WBSF, resilience, total, and insoluble collagen content than LTL (P < 0.05). When considering both muscles, total and insoluble collagen content were positively correlated (P < 0.05) with WBSF (r = 0.47 and 0.49, respectively), hardness (r = 0.49 and 0.50, respectively), cohesiveness (r = 0.50 and 0.50, respectively), chewiness (r = 0.58 and 0.59, respectively) and resilience (r = 0.63 and 0.63, respectively). The percentage of type III collagen content was negatively correlated (P < 0.05) with WBSF (r = -0.68) and hardness (r = -0.58). Collagen content was correlated (P < 0.05) with WBSF (r = 0.75) and hardness (r = 0.61) in LTL and with cohesiveness (r = 0.74) and resilience (r = 0.63) in BF. Collagen characteristics differ between muscles and contribute to pork texture in both LTL and BF.


Measurement of visual channels by contrast adaptation.
Inspection of a high-contrast grating pattern affects our ability to detect patterns that are similar. This technique can be used to infer the underlying mechanisms of the visual system. By using this technique, measurements of the bandwidth of orientation channels are taken for different levels of adapting contrast and adapting duration. If the threshold elevation is plotted as the difference between the unadapted and adapted threshold in decibels, then the orientation bandwidth is invariant if taken at some fraction of the maximum elevation. This results from the fact that, as the orientation difference between the adapting and test patterns increases, the function relating threshold elevation to adapting contrast reduces in slope. These data contradict the often-used 'equivalent contrast transformation' (in which the fall off in the adaptation effect with respect to orientation is expressed in terms of an equivalent reduction in adapting contrast) as this would produce quite different bandwidths at different adapting contrasts. The data also address the issue of the neuronal mechanisms of adaptation.


Erythrocyte lysis and angle-resolved light scattering measured by scanning flow cytometry result to 48 indices quantifying a gas exchange function of the human organism.
Molecular/cell level of gas exchange function assumes the accurate measurement of erythrocyte characteristics and rate constants concerning to molecules involved into the CO2 /O2 transport. Unfortunately, common hematology analyzers provide the measurement of eight indices of erythrocytes only and say little about erythrocyte morphology and nothing about rate constants of cellular function. The aim of this study is to demonstrate the ability of the Scanning Flow Cytometer (SFC) in the complete morphological analysis of mature erythrocytes and characterization of erythrocyte function via measurement of lysing kinetics. With this study we are introducing 48 erythrocyte indices. To provide the usability of application of the SFC in clinical diagnosis, we formed four categories of indices which are as follows: content/concentration (9 indices), morphology (26 indices), age (5 indices), and function (8 indices). The erythrocytes of 39 healthy volunteers were analyzed with the SFC to fix the first-ever reference intervals for the new indices introduced. The essential measurable reliability of the presented method is expressed in terms of errors of characteristics of single erythrocytes retrieved from the solution of the inverse light-scattering problem and errors of parameters retrieved from the fitting of the experimental kinetics by molecular-kinetics model of erythrocyte lysis.


[A peculiar form of anemia in patients operated on for cancer of the oral cavity].
The authors related about a peculiar form of anemia found in some patients operated on oral cancer; these patients had an almost normal hematic situation before their operation. 63 patients, operated in the course of a year for oral cancer, have been studied by the authors; they have found in 14 cases (22.2%) a light anemia which regressed after a self blood transfusion, during the first week after the operation; in other 8 cases (12.7%) the anemia, which was more serious, persisted beyond the 7th day after the operation. Those 8 patients, suffering from more serious and persistent anemia, were treated from 7th to 21st day after the operation with iron, vitamin B12 and folic acid without any improvement. The hematic situation improved about 10 days after the end of treatment, probably as a result of spontaneous renewal of medullar haemopoietic activity. This anemia, is characterized by normochromia, normocytosis, reduced response of reticulocytes, sideropenia and hyperferritinaemia. The authors think that the pathogenesis of anemia after operation in neoplastic patients is caused by medullary insufficiency existing before the operation, connected with reduced erythropoietin production and emphasized by an operation that sometimes cause bleeding. Consequently the authors hypothesis the use of erythropoietin in the therapy of most severe anemia in neoplastic operated patients.