The immediate effects of insulin and fructose on the metabolism of the perfused liver. Changes in lipoprotein secretion, fatty acid oxidation and esterification, lipogenesis and carbohydrate metabolism.
1. When livers from fed rats were perfused with blood containing elevated concentrations of rat insulin or blood to which fructose was added, the oxidation of free fatty acids was depressed and their esterification was increased. 2. Raised concentrations of insulin or addition of fructose increased secretion of triglyceride in very-low-density lipoproteins, but only insulin caused more of the free fatty acids taken up by the liver to be incorporated into very-low-density lipoproteins. 3. When insulin and fructose were added together the combined effect on oxidation and esterification of free fatty acids and on secretion of very-low-density lipoproteins was equal to the sum of the effects of either alone. No statistically significant interaction between the effects of fructose and insulin was found for any of the parameters investigated. 4. Bovine insulin had similar effects, in most respects, to comparable studies with raised concentrations of rat insulin. 5. Lipogenesis was increased in the livers treated with fructose plus bovine insulin. 6. A significant proportion of the fatty acids in very-low-density lipoproteins were derived either from the liver triglyceride pool or from lipogenesis. This fraction was increased both by treatment with insulin or fructose, and was augmented further when both insulin and fructose were present together. 7. The uptake of fructose by the perfused liver was similar to that found in vivo. It was unaffected by the presence of insulin. 8. Addition of fructose to the perfused liver caused perfusate lactate concentrations to increase, as a result of diminished hepatic uptake of lactate. 9. The uptake of free fatty acids by the perfused liver was unaffected by the addition of either insulin or fructose. 10. The distribution among the various lipid classes in plasma lipoproteins of label arising from the hepatic uptake of [(14)C]oleate was unaltered by the addition of either fructose or insulin. 11. It is suggested that the effects described are due principally to control of the balance between esterification of fatty acids and lipolysis of the ensuing triglyceride, fructose enhancing esterification and insulin inhibiting lipolysis.


Exploring the influences of geographical variation on sequence signatures in the human gut microbiome.
Geography shapes the structure and function of human gut microbiomes. In this study, we have explored the available human gut microbiome 16S rRNA sequence datasets of cohorts representing large geographical gradients. The 16S rRNA sequences representing V3-V4 as well as V4 regions generated using Illumina sequencing chemistry in the MiSeq platform encompassing the United States of America, Chile, South Africa, Kuwait, and Malaysia were subjected to in-depth computational biology analyses. Firmicutes and Bacteroidetes were the most dominant phyla present in all studied cohorts but Actinobacteria was exclusively present in high abundance in cohorts from Malaysia (15.99%). The relative abundance of five families, namely Bacteroidaceae, Ruminococcaceae, Prevotellaceae, Clostridiaceae, and Eubacteriaceae were highest representing the studied cohorts. The permutational multivariate analysis of variance (PERMANOVA) showed that the dissimilarity in the gut microbiome structure of cohorts representing studied countries was significant (R2 = 0.28, P<0.001). The calculated Firmicutes to Bacteroidetes (F : B) ratio was found to be lowest in cohorts from South Africa (1.11) and Chile (0.95). The cohorts from South Africa exhibited the highest alpha diversity based on Hill numbers at q=0, whereas at q=1 and 2, cohorts from Malaysia had the highest alpha diversity. The beta diversity analysis revealed that cohorts from Chile formed a distinct cluster among all the studied geographical locations. For the first time, the study also showed that cohorts from Malaysia representing short geographical distances exhibited distinct intrapopulation differences in the gut microbiome and may not be influenced by cultural and genetic factors.


Tracking of physical activity and aerobic power from childhood through adolescence.
To evaluate the tracking of physical activity levels (PA) and aerobic power (VO2max) in African-American (AA) and Caucasian (CA) youth as they age from 8 to 16 yr. Subjects were 529 girls and 535 boys for whom data were obtained at least three times over 7 yr and a subset of 387 girls and 404 boys who participated in all years. PA levels were obtained from a survey. VO2max was predicted from a cycle ergometer test. Spearman correlation for VO2max for years 1-7 for AA boys and girls were similar (rho approximately 0.53). Year 1-7 correlations for VO2max for the CA boys and girls were similar (rho approximately 0.50-0.53). The year 2-7 correlations for PA were similar for the AA and CA girls but higher for the AA than the CA boys. The kappa (kappa) statistics for VO2max indicated substantial year-to-year agreement on categorization (high, moderate, and low), with AA girls having the highest agreement and AA boys the lowest. The kappa statistic for high, moderate, and low PA groupings in girls of either ethnicity was quite low, whereas the kappa statistics for the boys were somewhat better. The general estimating equation (GEE) stability coefficients for tracking of VO2max were similar between the sexes and ethnicities (P<0.0001). The GEE stability coefficient for PA was better for the boys than girls and slightly better for the AA than CA. Although aerobic power and physical activity levels decline from childhood through adolescence, aerobic power tracks better than physical activity levels. Because tracking within the cohort is only moderate, change is possible if we intervene early in these youth.


Anatomic Structures at Risk When Utilizing an Intramedullary Nail for Distal Fibular Fractures: A Cadaveric Study.
Retrograde intramedullary fibular nail fixation is being utilized with increasing frequency, particularly in patients at higher risk of wound complications. The purpose of this anatomic study was to assess the relative risk to nearby anatomic structures when implanting a contemporary retrograde locked intramedullary fibular nail. Ten human cadaveric lower extremities were instrumented with a fibular nail. The cadavers were dissected. The shortest distance, in millimeters (mm), between the site of procedural steps and nearby named structures of interest (ie, sural nerve, superficial peroneal nerve, and the peroneal tendons) was measured and recorded. Levels of risk were assigned based on observed distances as high (0 to 5 mm), moderate (5.1-10 mm), and low (greater than 10 mm). The peroneus brevis (PB) tendon was found to be less than 5.0 mm from the distal skin incision in all specimens. When reaming and inserting the nail through the distal fibula aperture, the PB was less than 5.0 mm in 6 specimens. The peroneus longus tendon was at moderate to high risk when inserting both the proximal and distal syndesmotic screws in 9 specimens. The superficial peroneal nerve was at high risk when inserting an anterior to posterior distal locking screw in 7 specimens. The sural nerve was at low risk for all procedural steps. No structures were violated or damaged during any portion of the fibular nail instrumentation. The peroneal tendons and superficial peroneal nerve were at the highest risk; however, no structures were injured during instrumentation. The current findings indicate that strict adherence to sound percutaneous technique is needed in order to minimize iatrogenic damage to neighboring structures when performing retrograde locked intramedullary fibular nail insertion. This includes making skin-only incisions, blunt dissection down to bone, and maintaining close approximation between tissue protection sleeves and bone at all times.


Immunoglobulins M and G to varicella-zoster virus measured by solid-phase radioimmunoassay: antibody responses to varicella and herpes zoster infections.
Both immunoglobulin M (IgM) and IgG antibodies to varicella-zoster virus (VZV) were detectable in a solid-phase radioimmunoassay with 125I-labeled goat antisera to human immunoglobulins. Primary infection with VZV was associated with early production of IgM and IgG antibodies and rapid development of lymphocyte transformation to VZV antigen. Among eight subjects with varicella tested 1 to 4 days after onset, seven patients had IgG and six patients had IgM antibodies; all patients had both IgG and IgM antibodies within 7 days. An IgM response was documented by radioimmunoassay in 18 of 26 patients with herpes zoster. VZV antibodies could be assayed by radioimmunoassay in unfractionated serum with commercial goat antisera to human immunoglobulins and commercial VZV antigen. VZV-specific IgG binding was present in all sera from 42 subjects with a VZB antibody titer of greater than or equal to 1:8 as determined by indirect immunofluorescence and cellular immunity to VZV as determined by lymphocyte transformation and who had had varicella at least 20 years before testing. The geometric mean titer was 1:6,309, and titers were greater than or equal to 1:16,384 in 20 subjects. Antibody was present as determined by radioimmunoassay in 14 samples negative by complement fixation and in five samples negative by complement fixation and immune adherence hemagglutination. No specific binding was observed in 21 sera from subjects who were not immune to VZV as determined by indirect immunofluorescence or lymphocyte transformation despite the presence of herpes simplex or cytomegalovirus antibody indicated by complement fixation in 15 sera. High titers of VZV IgM antibody were detected in unfractionated sera despite the presence of high titers of VZV IgG antibody. The VZV radioimmunoassay provided a sensitive and practical method for measuring VZV IgG and IgM antibodies.


Structure and Dimension Effects on the Performance of Layered Triboelectric Nanogenerators in Contact-Separation Mode.
A triboelectric nanogenerator (TENG) is a potential solution for providing high output power by continuously harvesting ambient energy, which is expected to sustainably charge a battery for the new era-the era of the Internet of things and sensor networks. Generally, the existence of parasitic capacitance has been considered to be harmful in its output performance. Here, we systematically investigate the effects of structure and dimension of a TENG on its performance from the point view of parasitic capacitance by fabricating two types of layered TENGs with considering the dissimilarity of the two dielectric materials, symmetrical (ABBA) and alternate (ABAB) layered structure (SYM-TENG and ALT-TENG). Theoretical models of the two types of layered TENGs are proposed for illustrating their differences in parasitic capacitances and output characteristics. Larger parasitic capacitance enables the TENG to accommodate higher triboelectric charge density while reducing the internal impedance and maximum power density. Furthermore, the parasitic capacitance will be enhanced with the decreasing dimension of the devices. The effect of parasitic capacitance on output characteristics of the two kinds of structures are verified in vacuum. Our findings not only establish an optimization methodology for the output performance of TENGs but also provide an insight into the process of triboelectrification.


Glucagon like peptide-1 (GLP-1) dynamics following bariatric surgery: a Signpost to a new frontier.
Glucagon like peptide-1 (GLP-1) is one of the gastrointestinal peptides implicated in glycaemic homeostasis. In non-obese individuals with normal glucose tolerance GLP-1 is secreted in response to nutrient intake. However, this GLP- 1 response is generally accepted to be significantly diminished in those with diabetes, obesity or both. Given that GLP-1 is secreted from enteroendocrine L cells in the intestine, it is not surprising that manipulation of the gastro- intestinal tract has been shown to alter GLP-1 secretion; particularly when this intestinal manipulation is designed to aid weight reduction. GLP-1 dynamics are altered by bariatric surgery, with an improved secretory response to nutrient intake. However, there remains debate on the mechanisms responsible for the alterations in GLP-1 dynamics. Here we review the evidence for GLP-1 dynamics after Roux-en-Y gastric bpyass (RYGB), adjustable gastric banding (AGB), biliopancreatic diversion (BPD) and sleeve gastrectomy (SG), and make comparisons between modalities. In addition, we review the potential mechanisms underlying these dynamics, other molecules that may add to the "incretin effect" and other possible roles for GLP-1 following bariatric surgery. Finally, we will offer our critique of the evidence base.


CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge.
The transmembrane glycoprotein CD38 in airway smooth muscle is the source of cyclic-ADP ribose, an intracellular calcium-releasing molecule, and is subject to regulatory effects of cytokines such as interleukin (IL)-13, a cytokine implicated in asthma. We investigated the role of CD38 in airway hyperresponsiveness using a mouse model of IL-13-induced airway disease. Wild-type (WT) and CD38-deficient (CD38KO) mice were intranasally challenged with 5 microg of IL-13 three times on alternate days under isoflurane anesthesia. Lung resistance (R(L)) in response to inhaled methacholine was measured 24 h after the last challenge in pentobarbital-anesthetized, tracheostomized, and mechanically ventilated mice. Bronchoalveolar cytokines, bronchoalveolar and parenchymal inflammation, and smooth muscle contractility and relaxation using tracheal segments were also evaluated. Changes in methacholine-induced R(L) were significantly greater in the WT than in the CD38KO mice following intranasal IL-13 challenges. Airway reactivity after IL-13 exposure, as measured by the slope of the methacholine dose-response curve, was significantly higher in the WT than in the CD38KO mice. The rate of isometric force generation in tracheal segments (e.g., smooth muscle reactivity) was greater in the WT than in the CD38KO mice following incubation with IL-13. IL-13 treatment reduced isoproterenol-induced relaxations to similar magnitudes in tracheal segments obtained from WT and CD38KO mice. Both WT and CD38KO mice developed significant bronchoalveolar and parenchymal inflammation after IL-13 challenges compared with naïve controls. The results indicate that CD38 contributes to airway hyperresponsiveness in lungs exposed to IL-13 at least partly by increasing airway smooth muscle reactivity to contractile agonists.


Personality, burnout, and longevity among professional music therapists.
The purpose of this study was to examine possible relationships between personality, burnout level, longevity, and demographic variables among professional music therapists. The Sixteen Personality Factor Questionnaire (16PF) and the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) were used to test personality and burnout. Subjects were 137 professional music therapists from all seven American Music Therapy Association (AMTA) regions with an overall average longevity of 17.85 years. The 16PF showed the personality traits that most describe music therapists are emotional sensitivity, reasoning, apprehension, warmth, openness to change, self-reliance, extraversion, anxiety, abstractedness, rule-consciousness, and self-control. Logistic regressions showed that the personality factor of anxiety (p < .007) significantly predicts the MBI-HSS subscale of emotional exhaustion and the personality factor of dominance (p < .01) significantly predicts the MBI-HSS subscale of personal accomplishment. While no personality factor significantly predicts the MBI-HSS subscales of depersonalization, social boldness (p < 0.07) and vigilance (p < .09) strongly contributed to this relationship. Logistic regressions also showed that highest degree earned is significantly (p < .000) predictive of longevity. Since the overall burnout level was in the average range, in essence this study described the profile of music therapists who are staying and thriving in the profession.


Particulate composition characteristics under different ambient air quality conditions.
Particulate compositions including elemental carbon (EC), organic carbon (OC), water-soluble ionic species, and elemental compositions were investigated during the period from 2004 to 2006 in southern Taiwan. The correlation between the pollutant standard index (PSI) of ambient air quality and the various particle compositions was also addressed in this study. PSI revealed a correlation with fine (r = 0.74) and coarse (r = 0.80) particulate matter (PM). PSI manifested a significant correlation with the amount of analyzed ionic species (r approximately 0.80) in coarse and fine particles and a moderate correlation with carbon content (r = 0.63) in fine particles; however, it showed no correlation with elemental content. Although the ambient air quality ranged from good to moderate, the ionic species including chloride (Cl-), nitrate (NO3-), sulfate (SO4(2-)), sodium (Na+), ammonium (NH4+), magnesium (Mg2+), and calcium (Ca2+) increased significantly (1.5-3.7 times for Daliao and 1.8-6.9 times for Tzouying) in coarse PM. For fine particles, NO3-, SO4(2-), NH4+, and potassium (K+) also increased significantly (1.3-2.4 times for Daliao and 2.8-9.6 times for Tzouying) when the air quality went from good to moderate. For meteorological parameters, temperature evidenced a slightly negative correlation with PM concentration and PSI value, which implied a high PM concentration in the low-temperature condition. This reflects the high frequency of PM episodes in winter and spring in southern Taiwan. In addition, the mixing height increase from 980 to 1450 m corresponds to the air quality condition changing from unhealthy to good.


Neoplastic transformation of mouse fibroblasts by murine sarcoma virus: a multi-step process.
Infection of cultures of three different normal rodent cell lines with murine sarcoma virus (MSV) resulted in very rapid loss of contact inhibition of growth and morphological transformation. In the case of two of these lines, anchorage dependence of growth was also rapidly lost but with the 3rd, C3H10T1/2 C1.8, an established line of mouse embryo fibroblasts, there was a delay of many cell generations before the cells became anchorage independent. This was despite 100% successful infection, as assessed by focus assays of the infected cells. The acquisition of anchorage independence was correlated with a substantial increase in tumorigenicity. A number of MSV-infected clones, isolated at random from C3H10T1/2 C1.8 cultures immediately after infection with MSV, also showed a progressive increase in anchorage independence and tumorigenicity, indicating that the progressive transformation of the uncloned cells could not be entirely due to selection of rare anchorage-independent, tumorigenic clones. It was concluded that neoplastic transformation of C3H10T1/2 C1.8 cells by MSV is a multi-step process.


Development of a Novel Lung Slice Methodology for Profiling of Inhaled Compounds.
The challenge of defining the concentration of unbound drug at the lung target site after inhalation limits the possibility to optimize target exposure by compound design. In this study, a novel rat lung slice methodology has been developed and applied to study drug uptake in lung tissue, and the mechanisms by which this occurs. Freshly prepared lung slices (500 μm) from drug-naive rats were incubated with drugs followed by determination of the unbound drug volume of distribution in lung (Vu,lung), as the total concentration of drug in slices divided by the buffer (unbound) concentration. Vu,lung determined for a set of inhaled drug compounds ranged from 2.21 mL/g for salbutamol to 2970 mL/g for dibasic compound A. Co-incubation with monensin, a modulator of lysosomal pH, resulted in inhibition of tissue uptake of basic propranolol to 13%, indicating extensive lysosomal trapping. Partitioning into cells was particularly high for the cation MPP+ and the dibasic compound A, likely because of the carrier-mediated transport and lysosomal trapping. The results show that different factors are important for tissue uptake and the presented method can be used for profiling of inhaled compounds, leading to a greater understanding of distribution and exposure of drug in the lung.


Addressing comprehensive primary healthcare in Gujarat through mHealth intervention: Early implementation experience with TeCHO+ programme.
The Health and Family Welfare Department of Gujarat implemented a mHealth Programme called TeCHO+ (Technology for Community Health Operations) in 2018. TeCHO+ is aimed at making progress across all dimensions of the comprehensive primary healthcare services. The objective of this study is to record the document rollout and early implementation experience of TeCHO+ programme in Gujarat. The present participatory process documentation exercise was undertaken in Gujarat. The various steps for process documentation were decided after participation in multiple task force meetings and state/district- and taluka-level action seminars and reviewing the TeCHO+ programme data and progress reports. The perceptions of the health officials and field staff were gathered using key informant interviews from five districts of Gujarat: Bharuch, Narmada, Gandhinagar, Mahisagar, and The Dangs. In addition, stakeholders involved with TeCHO+ Programme were interviewed to understand the process of rollout, implementation challenges, and success. In the initial phase, the TeCHO+ application focussed only on updating the Family Health Survey to improve the quality of data captured in the system. FHWs log-in the mobile application daily to access their daily work plan for which SMS alerts were are also generated. Most FHWs were in their 50s and were first-time smartphone users. Although, they were enthusiastic and open to the new technology, initially they faced certain difficulties in operating the application. The programme had a strong troubleshooting mechanism in terms of the use of WhatsApp group, helpline numbers, and voice calls in addition to supportive supervision. TeCHO+ showed the potential to enhance the quality of the collected data and also service coverage. However, poor technology literacy of old FHWs, the launch of multiple programme memes at the same time, and target-driven task assignments pose major challenges.


Consent, wantedness, and pleasure: Three dimensions affecting the perceived stress of and judgements of rape in sexual encounters.
Participants conflate consent and wantedness when judging situations as rape (Peterson & Muehlenhard, 2007). Pleasure might also affect how such situations might be appraised by victims, perpetrators, and jurors. In four experiments, participants read vignettes describing sexual encounters that were consensual or not, wanted or unwanted, and pleasurable or not pleasurable. Participants judged whether they thought each situation described rape and how distressing they thought the encounter would be. Wantedness affected perceived distress when consent was given. Wantedness and pleasure also influenced whether participants considered the situation rape in nonconsensual scenarios. In additional experiments, we analyzed the results by gender, manipulated perspective (being the subject or initiator of the encounter), levels of aggression, and compared the results to a group of participants who had viewed an antiabuse campaign. Male participants and those higher in benevolent sexism were more likely than women to utilize pleasure and wantedness in judging whether situations described rape. Perspective and viewing the media campaign did not significantly affect judgments of rape. Our results have implications for models of the consequences of consent, wantedness, and pleasure of sex, and important implications for educational programs aimed at reducing sexual assault and training for those involved in criminal justice. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Short- and long-term effects of tactile massage on salivary cortisol concentrations in Parkinson's disease: a randomised controlled pilot study.
Parkinson's disease (PD) is a chronic neurodegenerative disorder with limited knowledge about the normal function and effects of non-pharmacological therapies on the hypothalamic-pituitary-adrenal (HPA) axis. The aim of the study was to analyse the basal diurnal and total secretion of salivary cortisol in short- and long-term aspects of tactile massage (TM). Prospective, Controlled and Randomised Multicentre Trial. Forty-five women and men, aged 50-79 years, were recruited. Twenty-nine of them were blindly randomised to tactile massage (TM) and 16 of them to the control group, rest to music (RTM). Ten interventions were given during 8 weeks followed by a 26 weeks of follow up. Salivary cortisol was collected at 8 am, 1 pm, 8 pm, and 8 am the next day, on five occasions. With the first and eighth interventions, it was collected immediately before and after intervention. The primary aim was to assess and compare cortisol concentrations before and immediately after intervention and also during the follow-up period. The secondary aim was to assess the impact of age, gender, body mass index (BMI), duration and severity of PD, effects of interventional time-point of the day, and levodopa doses on cortisol concentration. The median cortisol concentrations for all participants were 16.0, 5.8, 2.8, and 14.0 nmol/L at baseline, later reproduced four times without significant differences. Cortisol concentrations decreased significantly after TM intervention but no change in diurnal salivary cortisol pattern was found. The findings of reduced salivary cortisol concentrations immediately after the interventions are in agreement with previous studies. However, there was no significant difference between the TM and control groups. There were no significant correlations between cortisol concentrations and age, gender, BMI, time-point for intervention, time interval between anti-parkinson pharmacy intake and sampling, levodopa doses, duration, or severity of PD. Diurnal salivary cortisol rhythm was normal. Salivary cortisol concentrations were significantly reduced after the TM intervention and after RTM, but there were no significant differences between the groups and no sustained long-term effect. No associations were seen between salivary cortisol concentration and clinical and/or pharmacological characteristics. ClinicalTrial.gov, NCT01734876 and FoU Sweden 108881.


[Prevalence of physical abuse in childhood and exposure to parental violence in a Brazilian sample].
The aim of this study was to investigate the prevalence of physical abuse and exposure to parental violence during childhood, in relation to socio-demographic characteristics. Multi-stage sampling was used to select 3,007 individuals 14 years or older in 2005-2006, from all regions of the country. The study detected cases of physical abuse (beating, striking with objects, burning or scalding, threatening and/or using knives or firearms) and exposure to parental violence (witnessing parental threats and/or actual physical aggression) during childhood. Analyses were performed with the Pearson chi-square test. Prevalence of history of physical abuse in childhood was 44.1% (33.8% moderate, 10.3% severe). Prevalence of exposure to parental violence was 26.1% (7.5% witnessed moderate parental violence and 18.6% severe). Combined analyses of these two types of violence showed significant associations between them. The findings may help implement intervention strategies to call the attention of health professionals to the high prevalence of this type of violence.


High-dose cisplatin in patients with advanced malignancies.
A study was conducted to determine if cisplatin (CDDP) can be given at higher doses than usual, utilizing aggressive supportive measures. Twelve patients were entered into three dose levels of CDDP: level I, 180 mg/m2 given as a short infusion; level II, 220 mg/m2 also given as a short infusion; level III, 200 mg/m2 divided in five daily doses, each infused over 6 hours. In all cases, CDDP was dissolved and given in 250 ml of a 5% saline solution. For levels I and II, intravenous hydration with 200 to 250 ml/hour D5 1/2NS with potassium and magnesium supplements, was started 24 hours before therapy and continued for 3 to 4 days after, longer if nausea persisted. Mannitol was given before (25% solution, 50 ml bolus) and after (20% solution, 500 ml over 3 hours) CDDP. At level III hydration with the same intravenous (IV) fluids was begun the day before therapy and continued without interruption at 200 to 250 ml/hour for a minimum of 24 hours after the completion of the 5 days of chemotherapy. Each daily dose of CDDP was preceded by injection of mannitol (25% solution, 50 ml bolus) and accompanied by a 6-hour infusion of 1000 ml 20% mannitol. Three patients received five CDDP courses at level I; 4 patients, seven courses at level II; and 5 patients, seven courses at level III. Ototoxicity was dose-limiting in three patients at level II. Transient elevation of serum creatinine was seen following two courses at level I and two courses at level II. The renal impairment was asymptomatic in all cases; dialysis was not needed. At level II, leukocyte nadir counts between 1.0 and 2.0 X 10(3)/mm3 were seen following two courses and between 2.0 and 3.0 X 10(3)/mm3 following three courses. Platelet nadir counts below 50 X 10(3)/mm3 were recorded after four courses and between 50 and 100 X 10(3)/mm3 after one course. Nausea and vomiting occurred frequently, but were tolerable. At level III, myelosuppression was dose-limiting. Nadir leukocyte counts between 1.0 and 2.0 X 10(3)/mm3 followed four courses and between 2.0 and 3.0 followed one course. Nadir platelet counts below 50 X 10(3)/mm3 were seen after three courses; two patients required prophylactic platelet transfusions. Nadirs between 50 and 100 X 10(3) platelets/mm3 followed three further courses. Ototoxicity and nephrotoxicity did not occur at level III.(ABSTRACT TRUNCATED AT 400 WORDS)


Treatment of a cracked tooth with a resin-ionomer restoration and a connective tissue graft: a case report.
Treatment of a cracked tooth can be difficult and unpredictable. Quite often, the most predictable treatment possible is simply extraction. This is a case report of the treatment of a cracked tooth with a resin-ionomer restoration and a connective tissue with partial-thickness double pedicle graft. The crack was detected during a routine root coverage procedure using this type of graft. A resin-ionomer was used to repair the crack. Then, the root coverage procedure was completed. Complete root coverage was obtained, including the portion of the root that was repaired. The results remained stable and the tooth treated remained asymptomatic. Clinically, the treatment was a success.


Barriers to physical activity among working mothers.
Working mothers experience several barriers to physical activity. If these barriers can be identified by occupational health nurses and they can partner with working mothers to reduce these perceived barriers, the health of these workers can be improved and chronic disease risk prevented. The purpose of this study was to measure the effect of self-regulatory efficacy on physical activity among working mothers and to describe specific barriers to physical activity. The Barriers Specific Self-Efficacy Scale (BARSE) and the Kaiser Physical Activity Survey (KPAS) were used to measure the variables. Self-regulatory efficacy was found to be a strong predictor of physical activity in a diverse sample of working mothers who did not meet current recommendations for physical activity. Occupational health nurses can use these findings to design programs for groups and for counseling individuals.


Decomposition of three-dimensional objects into spheres.
Algorithms are presented for converting between different three-dimensional object representations: from a collection of cross section outlines to surface points, and from surface points to a collection of overlapping spheres. The algorithms effect a conversion from surface representations (outlines or surface points) to a volume representation (spheres). The spherical representation can be useful for graphical display, and perhaps as an intermediate representation for conversions to representations with other primitives. The spherical decomposition also permits the computation of points on the symmetric surface of an object, the three-dimensional analog of Blum's symmetric axis. The algorithms work in real coordinates rather than in a discrete space, and so avoid error introduced by the quantization of the space.


Incorporation of label from(1- 14 C)ethanol into the glutamate-glutamine pools of rat brain in vivo.
Glutamate and glutamine were isolated from the brains of rats given [1-(14)C]ethanol by three different routes of injection with and without carrier ethanol or acetate. Without exception, the specific radioactivity of brain glutamine was 3- to 5-fold that of brain glutamate. The route of injection had no consistent effect on the results. These results indicate that small amounts of ethanol are oxidized by rat brain in the compartment responsible for the so-called ;small metabolic pool' of brain glutamate.


Influences of the aging process on acute perioperative pain management in elderly and cognitively impaired patients.
The aging process results in physiological deterioration and compromise along with a reduction in the reserve capacity of the human body. Because of the reduced reserves of mammalian organ systems, perioperative stressors may result in compromise of physiologic function or clinical evidence of organ insult secondary to surgery and anesthesia. The purpose of this review is to present evidence-based indications and best practice techniques for perioperative pain management in elderly surgical patients. In addition to pain, cognitive dysfunction in elderly surgical patients is a common occurrence that can often be attenuated with appropriate drug therapy. Modalities for pain management must be synthesized with intraoperative anesthesia and the type of surgical intervention and not simply considered a separate entity. Pain in elderly surgical patients continues to challenge physicians and healthcare providers. Current studies show improved surgical outcomes for geriatric patients who receive multimodal therapy for pain control.


Assessing the capacity of the health services research community in Australia and New Zealand.
BACKGROUND: In order to profile the health services research community in Australia and New Zealand and describe its capacity, a web-based survey was administered to members of the Health Services Research Association of Australia and New Zealand (HSRAANZ) and delegates of the HSRAANZ's Third Health Services Research and Policy Conference. RESULTS: Responses were received from 191 individuals (68%). The responses of the 165 (86%) who conducted or managed health services research indicated that the health services research community in Australia and New Zealand is characterised by highly qualified professionals who have come to health services research via a range of academic and professional routes (including clinical backgrounds), the majority of whom are women aged between 35 and 54 who have mid- to senior- level appointments. They are primarily employed in universities and, to a lesser extent, government departments and health services. Although most are employed in full time positions, many are only able to devote part of their time to health services research, often juggling this with other professional roles. They rely heavily on external funding, as only half have core funding from their employing institution and around one third have employment contracts of one year or less. Many view issues around building the capacity of the health services research community and addressing funding deficits as crucial if health services research is to be translated into policy and practice. Despite the difficulties they face, most are positive about the support and advice available from peers in their work settings, and many are actively contributing to knowledge through academic and other written outputs. CONCLUSION: If health services research is to achieve its potential in Australia and New Zealand, policy-makers and funders must take the concerns of the health services research community seriously, foster its development, and contribute to maximising its capacity through a sustainable approach to funding. There is a clear need for a strategic approach, where the health services research community collaborates with competitive granting bodies and government departments to define and fund a research agenda that balances priority-driven and investigator-driven research and which provides support for training and career development.


Clinical Application of Anomalous Muscles for Tendon Transfer in the Upper Limb: A Systematic Review of the Literature.
Numerous anomalous muscles of the forearm and hand have been reported in the literature. The majority were encountered in cadaver dissections and some were incidentally detected during tendon transfer surgery. Because of the limited number of motors available for transfer, it may be advantageous if an anomalous muscle with favorable anatomy can function as a potential donor in a suitable clinical environment. Although several authors have illustrated various anomalies and their functional significance, the reports of actual utilization of such muscles as donors for tendon reconstructions are sparse. The aim of the study is to conduct a systematic review of the clinical applications of anomalous muscles in the upper extremity. After a thorough search of PubMed, Web of Science, Scopus, and Cochrane Library databases, only three out of 106 studies were found to be relevant. Two of them discussed the anomalous radial wrist extensor tendon transfer for thumb flexion. The third study described the usage of anomalous flexor carpi ulnaris (FCU) for thumb opposition and index finger flexion, and also proposed a classification. This is the first systematic review of the clinical application of anomalous muscles as donors in the upper extremity tendon transfer surgical procedures. Knowledge of the above classification helps in intraoperative evaluation of the type of the anomaly and the possible consideration of anomalous muscle as a source of transplant material in an appropriate clinical setting.


Quantitative measurement of oxygen extraction fraction by MRI in patients with cerebrovascular disease: pre- and post-surgery.
We aimed to evaluate cerebral hemodynamic status of preoperative and postoperative revascularization treatment by oxygen extraction fraction (OEF)-magnetic resonance imaging (MRI) in patients with severe cerebrovascular stenosis or occlusive disease. This study enrolled 9 symptomatic patients with severe cerebrovascular disease and 9 age-matched normal volunteers. Cerebral blood flow (CBF) and OEF were determined in all subjects by functional MRI. Brain regions with elevated OEF above normal range were defined in the patients preoperatively. The values of pre- and postoperative OEF in these regions were compared. A total of 16 regions of interest (ROIs) had elevated OEF before the vascular surgery, with relative CBF (rCBF) values ranging from 0.2 to 1.0. OEF decreased to normal range in 15 ROIs postoperatively, which indicated hemodynamic improvement in these regions. The OEF value of the high-OEF group (preoperative OEF value ranged from 0.365 to 0.400) had a significant decrease compared with those of the low-OEF group (preoperative OEF value ranged from 0.350 to 0.365), which showed an a statistical difference (p = 0.001). OEF was elevated in patients with severe ischemic cerebrovascular disease, and decreased after successful revascularization. OEFMRI can provide quantitative information for evaluating the hemodynamic status and selecting the candidates suitable for revascularization.


A Japanese Case of Esophageal Lichen Planus that Was Successfully Treated with Systemic Corticosteroids.
Esophageal lichen planus (ELP) is rare and only about 80 cases have been reported in the literature. An 85-year-old woman presented with dysphagia and odynophagia. Endoscopy revealed a severe stricture in the proximal esophagus. Oral examinations at two years after the first endoscopy revealed erosions around the gingiva, and an examination of biopsy specimens taken from the site of erosion led to a diagnosis of oral lichen planus. Esophageal endoscopy was performed again, and biopsy specimens showed spongiosis and necrotic keratinocytes in the epithelium (civatte bodies). The patient was diagnosed with ELP and was treated with systemic corticosteroids, which resulted in clinical relief.


Insulin stimulates volume absorption in the rabbit proximal convoluted tubule.
The present in vitro microperfusion study examined whether insulin affects volume absorption (Jv) in the proximal convoluted tubule (PCT). PCT were perfused with an ultrafiltrate-like solution and were bathed in a serum-like albumin solution. Addition of a physiologic concentration of 10(-10) M insulin to the bathing solution resulted in a stimulation of Jv and a more negative transepithelial potential difference (PD). There was a progressive stimulation of the lumen negative PD and Jv with higher insulin concentrations. Maximal stimulation occurred at 10(-8) M bath insulin. The insulin-induced stimulation of volume reabsorption was also observed when glucose and amino acids were removed from the luminal perfusate. Direct examination of the effect of insulin on glucose, chloride, and bicarbonate absorption demonstrated that the transport of all these solutes was stimulated by insulin. Addition of insulin to the luminal perfusate had no affect on Jv. These data show that insulin has a direct effect to stimulate Jv in the proximal tubule.


Clofazimine, a Promising Drug for the Treatment of Babesia microti Infection in Severely Immunocompromised Hosts.
Persistent and relapsing babesiosis caused by Babesia microti often occurs in immunocompromised patients, and has been associated with resistance to antimicrobial agents such as atovaquone. Given the rising incidence of babesiosis in the United States, novel drugs are urgently needed. In the current study, we tested whether clofazimine (CFZ), an antibiotic used to treat leprosy and drug-resistant tuberculosis, is effective against B. microti. Mice with severe combined immunodeficiency were infected with 107B. microti-infected erythrocytes. Parasites were detected by means of microscopic examination of Giemsa-stained blood smears or nested polymerase chain reaction. CFZ was administered orally. Uninterrupted monotherapy with CFZ curtailed the rise of parasitemia and achieved radical cure. B. microti parasites and B. microti DNA were cleared by days 10 and 50 of therapy, respectively. A 7-day administration of CFZ delayed the rise of parasitemia by 22 days. This rise was caused by B. microti isolates that did not carry mutations in the cytochrome b gene. Accordingly, a 14-day administration of CFZ was sufficient to resolve high-grade parasitemia caused by atovaquone-resistant B. microti parasites. Clofazimine is effective against B. microti infection in the immunocompromised host. Additional preclinical studies are required to identify the minimal dose and dosage of CFZ for babesiosis.


Fat Grafting after Invasive Breast Cancer: A Matched Case-Control Study.
Fat grafting has been widely indicated for postmastectomy and postlumpectomy breast reconstruction. The literature emphasizes the clinical efficacy of fat grafting, but experimental studies raise important questions about the recurrence risk because of the stimulation of remaining cancer cells by progenitor or adult adipocytes. Because breast conservative treatment provides a higher risk of residual cancer cells in the breast tissue compared with mastectomy, the authors set up a matched case-control study of fat grafting versus no fat grafting after breast conservative treatment. The authors collected data from 322 consecutive patients operated on for a primary invasive breast cancer who subsequently underwent fat grafting for breast reshaping from 2006 to 2013. All patients were free of recurrence before fat grafting. For each patient, the authors selected one patient with similar characteristics who did not undergo fat grafting. After a mean follow-up of 4.6 years (range, 0.1 to 10.2 years) after fat grafting, or a corresponding time for controls, the authors observed no difference in the incidence of local events (fat grafting, n = 14; controls, n = 16; p = 0.49), axillary nodes metastasis (fat grafting, n = 3; controls, n = 6; p = 0.23), distant metastases (fat grafting, n = 14; controls, n = 15; p = 0.67), or contralateral breast cancer (fat grafting, n = 4; controls, n = 4; p = 0.51). Fat grafting seems to be a safe procedure after breast conservative treatment for breast cancer patients. Therapeutic, III.


From {Au(I)···Au(I)}-coupled cages to the cage-built 2-D {Au(I)···Au(I)} arrays: Au(I)···Au(I) bonding interaction driven self-assembly and their Ag(I) sensing and photo-switchable behavior.
Metal-metal bonding interactions have been used to generate a number of unique supramolecular assemblies with fascinating functions. We presented here a new class of gold(I)-containing metallosupramolecular cages and cage-built two-dimensional (2-D) arrays of {Au8L2}n (n = 1 or ∞, L = tetrakis-dithiocarbamato-calix[4]arene, TDCC), 1-3, which are constructed from the self-assembly of deep-cavitand calix[4]arene-based supramolecular cages consisting of octanuclear Au(I) motifs. Synchrotron radiation X-ray diffraction structural analyses of 1-3 revealed their quadruple-stranded helicate dimeric cage structure and the presence of 2-D arrays of cages linked together by inter- and intramolecular Au(I)···Au(I) interactions. Electronic absorption and emission studies of complexes 1-3 indicated the occurrence of a programmable self-assembly process in a concentration-dependent stepwise manner with the links built via aurophilic interactions. These novel gold(I) supramolecular cages exhibited green phosphorescence and have been shown to serve as highly selective proof-of-concept luminescent sensors toward Ag(I) cation among various competitive transition-metal ions.


Free-running 5D coronary MR angiography at 1.5T using LIBRE water excitation pulses.
To implement, optimize, and characterize lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses for fat-suppressed fully self-gated free-running 5D cardiac MRI. Bloch equation simulations were used to optimize LIBRE parameter settings in non-interrupted bSSFP prior to in vitro validation. Thus, optimized LIBRE pulses were subsequently applied to free-running coronary MRA in 20 human adult subjects, where resulting images were quantitatively compared to those obtained with non-fat-suppressing excitation (SP), conventional 1-2-1 water excitation (WE), and a previously published interrupted free-running (IFR) sequence. SAR and scan times were recorded. Respiratory-and-cardiac-motion-resolved images were reconstructed with XD-GRASP, and contrast ratios, coronary artery detection rate, vessel length, and vessel sharpness were computed. The numerically optimized LIBRE parameters were successfully validated in vitro. In vivo, LIBRE had the lowest SAR and a scan time that was similar to that of WE yet 18% shorter than that of IFR. LIBRE improved blood-fat contrast when compared to SP, WE, and IFR, vessel detection relative to SP and IFR, and vessel sharpness when compared to WE and IFR (for example, for the left main and anterior descending coronary artery, 51.5% ± 10.2% [LIBRE] versus 42.1% ± 6.8% [IFR]). Vessel length measurements remained unchanged for all investigated methods. LIBRE enabled fully self-gated non-interrupted free-running 5D bSSFP imaging of the heart at 1.5T with suppressed fat signal. Measures of image quality, vessel conspicuity, and scan time compared favorably to those obtained with the more conventional non-interrupted WE and the previously published IFR, while SAR reduction offers added flexibility.


Plastic additives: challenges in ecotox hazard assessment.
The risk of plastic debris, and specifically micro(nano)plastic particles, to ecosystems remains to be fully characterized. One particular issue that warrants further characterization is the hazards associated with chemical additives within micro(nano)plastic as they are not chemically bound within the polymers and can be persistent and biologically active. Most plastics contain additives and are therefore potential vectors for the introduction of these chemicals into the environment as they leach from plastic, a process that can be accelerated through degradation and weathering processes. There are knowledge gaps on the ecotoxicological effects of plastic additives and how they are released from parent plastic materials as they progressively fragment from the meso to micro and nano scale. This review summarizes the current state of knowledge of the ecotoxicity of plastic additives and identifies research needs to characterize the hazard they present to exposed biota. The potential ecological risk of chemical additives is of international concern so key differences in governance between the European Union and New Zealand to appropriately characterize their risk are highlighted.


Norwich terriers possess a greater vertebral heart scale than the canine reference value.
Previous studies have demonstrated evidence that normal reference ranges for radiographic vertebral heart scale values can vary among dog breeds. The purpose of this retrospective, observational study was to determine whether the normal vertebral heart scale values published by Buchanan and Bücheler for lateral radiographs are applicable to the Norwich terrier. Secondary objectives were to determine if clinical signs of respiratory disease, age, sex, weight, body condition score, recumbency, or thoracic depth-to-width ratio had any influence on vertebral heart scale measurements in this breed. The electronic medical record systems of two universities were reviewed and Norwich terriers were included in the study if they had orthogonal thoracic radiographs performed and no historical or radiographic evidence of cardiopulmonary disease. A vertebral heart scale was calculated for each patient. Sixty-one client-owned, Norwich terrier dogs with no clinical signs of cardiovascular disease were evaluated. The vertebral heart scale for Norwich terriers without evidence of cardiac disease (10.6 ± 0.6) was found to be significantly greater than the canine reference value of 9.7 ± 0.5 initially established by Buchanan and Bücheler. No significant correlation was found between clinical signs of respiratory disease, sex, age, thoracic depth-to-width ratio or lateral recumbency, and vertebral heart scale. Norwich terriers with a body condition score ≥6 had a significantly higher vertebral heart scale than those with a body condition score ≤5. Breed-specific ranges and body condition scores need to be considered when interpreting vertebral heart scale values for Norwich terriers.


An estimation of traffic related CO2 emissions from motor vehicles in the capital city of, Iran.
Vehicle exhaust is a major source of anthropogenic carbon dioxide (CO2) in metropolitan cities. Popular community mode (buses and taxies) and about 2.4 million private cars are the main emission sources of air pollution in Tehran. A case survey has conducted to measure CO2 in four popular vehicles, bus, taxi, private car and motorcycle, which moved in the city with respectively 7800, 82358, 560000 and 2.4 million per day in 2012. Results indicated that the contribution of CO2 emissions increased in the following order: private car, motorcycle, bus and taxi. The overall average for the contribution of CO2 emissions in the private car, motorcycle, bus, and taxi were 26372, 1648, 1433 and 374 tons per day, respectively. Our results also showed that the urban transport operation consume an estimated 178 and 4224 million liter diesel and petrol per year, respectively, that have released about 10 million tons of CO2. The average contribution of CO2 emissions of private cars in Tehran was higher (88%) than other vehicles. It was concluded that high volume of traffic, transport consumption of fossil fuels and shortage of adequate public transport system are responsible for the high CO2 level in environment in Tehran. Thus, it is to be expected that CO2 as a greenhouse gas has risen in Tehran more than ever in the following years and this would be a matter of concern for the authorities to have a comprehensive plan to mitigate this phenomena.


Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program.
Avelumab, a human anti-programmed death-ligand 1 immunoglobulin G1 monoclonal antibody, showed favorable efficacy and safety in patients with metastatic Merkel cell carcinoma (mMCC) in the phase II JAVELIN Merkel 200 trial, leading to approval in multiple countries. We describe real-world experience with avelumab in patients with mMCC from an expanded access program. Eligible patients had mMCC and progressive disease during or after chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received an initial 3-month supply of avelumab (administered as 10 mg/kg intravenously every 2 weeks until progressive disease or unacceptable toxicity); resupply was allowed following complete response, partial response, stable disease, or clinical benefit per physician assessment. Between December 15, 2015, and March 4, 2019, 558 of 620 requests from 38 countries were medically approved, and 494 patients received avelumab. Among 240 evaluable patients, the objective response rate was 46.7% (complete response in 22.9%, including 3 of 16 potentially immunocompromised patients), and the disease control rate was 71.2%. The median duration of treatment in evaluable patients with response was 7.9 months (range, 1.0-41.7) overall and 5.2 months (range, 3.0-13.9) in immunocompromised patients. No new safety signals were identified. The expanded access program closed for new requests on December 31, 2018, as required after regulatory approval; benefitting patients continued to receive avelumab. The avelumab expanded access program for patients with mMCC demonstrated efficacy and safety in a real-world setting, consistent with the results from JAVELIN Merkel 200, and provided a treatment for patients with limited options.


[The treatment of patients with the anococcygeal pain syndrome].
Results are reported of a two-year rehabilitative treatment of 17 patients with anococcygeal pain syndrome. The I stage of treatment consisted of intrarectal administration of anti-inflammatory reparative anesthetic aerosols "Olasol" and "Cimesol" in association with phonophoresis on the lumbosacral zone. At the 11 stage prophylaxis of recurrences was carried out by dietary and physiotherapeutic correction of constipation as well as short repeat courses of "soft" aerosols "Livian", "Levovinisol" or "Vinisol" in association with phonophoresis every 4-6 months. The medical and economic efficacy of the method is emphasized. Recurrences were 3.5 times less frequent.


Isolation and characterization of an extracellular lipase from the conidia of Neurospora crassa.
A triacylglycerol lipase (EC 126.96.36.199) from the conidia of Neurospora crassa was purified and characterized. The enzyme was purified by Sephadex G-100 column chromatography. Homogeneity was checked by PAGE, and isoelectric focusing gave a single band corresponding to a pI of 6.4. The enzyme had an apparent Mr 54000 +/- 1000 as determined by gel filtration. SDS-PAGE gave a single band of Mr 27000, suggesting the presence of two identical subunits. This lipase preferred triglycerides with C16- and C18-fatty acyl chains. It cleaved only the primary groups of triglycerides. The lipase also exhibited a marked preference for substrates containing endogenously occurring fatty acids and so may prove useful in detailed studies on the physiological relevance of fatty acyl specificity of lipases. The enzyme was not affected by detergents, or thiol-binding agents. Modification of free amino groups caused 90% inhibition, suggesting a role of these groups in the maintenance of lipase activity.


Echinococcosis in Libya. IV. Prevalence of hydatidosis (Echinococcus granulosus) in goats, cattle and camels.
During a survey of 14 Libyan abattoirs in 1985-1987 the carcasses of 4316 locally-bred goats, cattle and camels were inspected for cysts of Echinococcus granulosus. Of 2295 goats, 35 adults (1.5%) had cysts; no kids were infected. Thirty-one adult goats had infected livers, 28 had lung infections, and four each had cysts in their kidneys and spleens. Most (59.7%) of the infections were light, with medium infections in 31.3% and heavy infections in 8.9%; 85.7% of the cysts in the lungs and 38.7% of those in the livers were fertile; three of the four kidney infections and two of the four spleen infections were fertile. Of the 1023 cattle carcasses, mild infections with E. granulosus were seen in 55 (5.4%); all the cysts were sterile and confined to the liver. Of 998 camels, 358 (35.9%) had hydatid cysts. These involved the lungs in 96.9%, either as the sole site (74.3%) or jointly with the liver (22.6%). Lung cysts (57.6%) and liver cysts (41.2%) were fertile.


Relationships of contextual and relational factors to health empowerment in women.
The purpose of this study was to determine the relationships of contextual and relational factors to health empowerment in women with children. This study used a descriptive, correlational design to answer the basic research question: "What contextual and relational factors explain health empowerment in women?" The theoretical framework of health empowerment was based upon a synthesis of social and developmental perspectives and guided by a Rogerian view of the person-environment process. The analytic approach included bivariate correlations and a series of multiple regressions to identify factors explaining health empowerment. The contextual (demographic) and relational (social and professional support) factors explained 38% of the variance in health empowerment measured as knowing participation in change. For health empowerment, measured as lifestyle behaviors, the contextual and relational factors explained 43% of the variance. The results of this study offer partial empirical support for theoretical relationships. Findings provide a basis to generate additional nursing research focusing on the continuous mutual process of human beings and the environment, leading to theory-based interventions.


Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population: the Takahata study.
A cluster of proinflammatory cytokines plays an important role in the development of various renal diseases, and the expression of these cytokines is genetically modified. To examine the association between polymorphisms of proinflammatory cytokine genes and albuminuria, a cross-sectional study was conducted in the general population. Single nucleotide polymorphisms (SNPs) in six proinflammatory cytokine genes, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, CC chemokine ligand 1 (CCL1) and monocyte chemoattractant protein-1 (MCP-1), were genotyped in 2927 Japanese subjects. Urine albumin-creatinine ratio (UACR) was measured in morning spot urine samples. Albuminuria (UACR ≥ 30 mg/g) was significantly associated with the A/A + A/G genotype at rs2069852 in the IL-6 gene (P = 0.01) and the A/A genotype at rs228269 in the CCL1 gene (P = 0.002). Multivariate analysis with adjustment for traditional risk factors showed that these genotypes independently predicted albuminuria [odds ratio (OR) 1.782, 95% confidence interval (CI) 1.171-2.712, P = 0.007 for the A/A + A/G genotype at rs2069852 in IL-6, and OR 1.432, 95% CI 1.128-1.770, P = 0.003 for the A/A genotype at rs228269 in CCL1]. The prevalence of albuminuria and the UACR were increased along with the increase of risk genotypes. This study revealed that SNPs in the IL-6 and CCL1 genes were associated with albuminuria, and the combination of these genotypes had an additive effect on the prevalence and severity of albuminuria. This indicates that genetic factors influencing inflammatory responses may affect the development of renal injury in the Japanese general population.


Protein-selective adsorbers by molecular imprinting via a novel two-step surface grafting method.
Molecularly imprinted polymers (MIP) offer in principle a robust, cost-efficient alternative to antibodies, but it is still a challenge to develop such materials for protein recognition. Here, we report the molecular imprinting of a functional polymeric hydrogel layer with lysozyme as the template in a two-step grafting procedure by a novel initiation approach on track-etched polyethylene terephthalate membrane surface. This is based on surface functionalization with aliphatic C-Br groups which can be used as an initiator for surface-initiated atom transfer radical polymerization (SI-ATRP) and photo-initiated copolymerization. At first, the scaffold poly(methacrylic acid) (PMAA) was obtained through SI-ATRP of poly(tert-butyl methacrylate) and subsequent hydrolysis. Thereafter, it was assembled with the template to form a stable PMAA/lysozyme complex. In the second step, a polyacrylamide (PAAm) hydrogel was synthesized via UV-initiated surface grafting/crosslinking copolymerization around the scaffold/protein complex. Finally, the template was eluted to yield the grafted hydrogel layer with binding sites having complementary size, shape and appropriate arrangement of the functional groups to rebind lysozyme. The selectivity of lysozyme recognition, relative to cytochrome C with a similar size and isoelectric point, was increased by optimization of the scaffold chain length, UV grafting/crosslinking time and the chemical crosslinking degree of the PAAm-based hydrogel. The feasibility for the development of protein MIP in a straightforward way by independent optimization of crucial parameters - structures of scaffold with functional groups and of the crosslinked hydrogel matrix - have been demonstrated.


Membrane fluidity determines sensitivity of filamentous fungi to chitosan.
The antifungal mode of action of chitosan has been studied for the last 30 years, but is still little understood. We have found that the plasma membrane forms a barrier to chitosan in chitosan-resistant but not chitosan-sensitive fungi. The plasma membranes of chitosan-sensitive fungi were shown to have more polyunsaturated fatty acids than chitosan-resistant fungi, suggesting that their permeabilization by chitosan may be dependent on membrane fluidity. A fatty acid desaturase mutant of Neurospora crassa with reduced plasma membrane fluidity exhibited increased resistance to chitosan. Steady-state fluorescence anisotropy measurements on artificial membranes showed that chitosan binds to negatively charged phospholipids that alter plasma membrane fluidity and induces membrane permeabilization, which was greatest in membranes containing more polyunsaturated lipids. Phylogenetic analysis of fungi with known sensitivity to chitosan suggests that chitosan resistance may have evolved in nematophagous and entomopathogenic fungi, which naturally encounter chitosan during infection of arthropods and nematodes. Our findings provide a method to predict the sensitivity of a fungus to chitosan based on its plasma membrane composition, and suggests a new strategy for antifungal therapy, which involves treatments that increase plasma membrane fluidity to make fungi more sensitive to fungicides such as chitosan.


Microbial flora in orodental infections.
The present study was carried out to compare the normal aerobic and anaerobic bacterial oral flora with flora from deep seated dental caries, gingivitis and adult periodontitis. All the samples belonging to both the control and study groups yielded microbes. Aerobe / Anaerobe ratio was high in normal flora (1.48) as compared to dental caries (0.9), gingivitis (0.72) and periodontitis (0.56). Ninety seven percent of orodental infections were polymicrobial and three or more microbes were found in 84% cases of study group as compared to 28% in controls. Streptococcus mutans and anaerobic lactobacilli were common in dental caries, Actinomyces and Peptostreptococcus spp. in gingivitis, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in periodontitis.


Evaluating the Ecological Footprint of Landfills: A Framework and Case Study of Fargo, North Dakota.
There is growing interest in better understanding the environmental impacts of landfills and optimizing their operation. Accordingly, we developed a holistic framework to calculate a landfill's Ecological Footprint (EF) and applied that to the Fargo, North Dakota, landfill. Parallelly, the carbon footprint and biocapacity of the landfill were calculated. We calculated the EF for six scenarios (i.e., cropland, grazing land, marine land, inland fishing ground, forest land, and built land as land types) and six operational strategies typical for landfills. Operational strategies were selected based on the variations of landfill equipment, the gas collection system, efficiency, the occurrence of fugitive emissions, and flaring. The annual EF values range from 124 to 213,717 global hectares depending on land type and operational strategy. Carbon footprints constituted 28.01-99.98% of total EF, mainly driven by fugitive emissions and landfill equipment. For example, each percent increase in Fargo landfill's fugitive emissions caused the carbon footprint to rise by 2130 global hectares (4460 tons CO2e). While the landfill has biocapacity as grazing grass in open spaces, it remains unused/inaccessible. By leveraging the EF framework for landfills, operators can identify the primary elements contributing to a landfill's environmental impact, thereby minimizing it.


The Arabic version of the ABILOCO-Kids scale is valid and reliable in children with cerebral palsy.
Background: The ABILOCO-Kids is a parent-reported outcome measure that quantifies locomotion ability and has been reported to have satisfactory measurement properties. An Arabic version of the scale is needed for Arabic-speaking population.Objective: To cross-culturally adapt the ABILOCO-Kids into Arabic and to examine its measurement properties in children with cerebral palsy.Methods: Forward and backward translations, then expert committee followed by preliminary testing were conducted to produce the Arabic ABILOCO-Kids. Structural validity of the scale as a unidimensional measure was examined using Rasch analysis. Internal consistency, test-retest reliability, and construct validity of the adapted scale were examined in children with cerebral palsy (N = 154).Results: Rasch analysis supported the structural validity of the Arabic ABILOCO-Kids after combining two items (χ2 = 18.17, p = .44). The scale had excellent internal consistency (person separation index = 0.88), excellent test-retest reliability (intraclass correlation coefficient = 0.98) but had a floor effect (24% reaching the minimum score). Eighty percent of the predefined hypotheses regarding the correlation between the Arabic ABILOCO-Kids and the Gross Motor Function Classification System (GMFCS) (r = -0.65) and the Functional Independence Measure for Children (WeeFIM) subscales (r = 0.34 to 0.70) were supported by the results.Conclusion: The Arabic ABILOCO-Kids is a unidimensional interval-level measure of walking ability in children with cerebral palsy with evidence supporting its structural validity, internal consistency, test-retest reliability and construct validity.


Predictors and mode of death over 5 years amongst patients admitted to the emergency department with acute chest pain or other symptoms raising suspicion of acute myocardial infarction.
To describe the mortality and mode of death over 5 years, and factors associated with death amongst patients with acute chest pain. All patients who came to the emergency department at Sahlgrenska Hospital in Göteborg with acute chest pain or other symptoms raising suspicion of acute myocardial infarction (AMI) during a 21-month period. In all, 5241 patients were evaluated, of whom 1345 (26%) died during the 5 years of follow-up. The following factors were independent predictors male sex (P < 0.001); symptoms of acute congestive heart failure (P < 0.001) or unspecific symptoms on admission (P < 0.05); smoking (P < 0.001); a history of either congestive heart failure (P < 0.001), diabetes mellitus (P < 0.001), previous myocardial infarction (P < 0.001) or hypertension (P < 0.05); initial degree of suspicion of AMI (P < 0.001) and presence of pathological electrocardiogram (P < 0.001) on admission to hospital. Amongst patients who died, 66% died a cardiac death and 35% died in association with a myocardial infarction. Amongst patients admitted to the emergency department due to chest pain or other symptoms raising suspicion of AMI, several predictors based on clinical history and clinical presentation can be defined, which are strongly related to the long-term prognosis.


Online learning: enhancing nurse education?
The need to integrate information technology into nursing education has been recognized and well documented. In spite of this, information technology remains a neglected subject in many nursing programmes. Strategies have been considered for increasing the integration of information technology in nursing education. One of the key issues identified is the need for research into the factors that contribute to optimal learning with information technology, specifically the need to explore issues that contribute to student frustration and satisfaction with learning. Within Australia, the incorporation of information technology as a core subject in nursing education is still relatively new. This article describes how one university used 'online' learning to expose students to conceptual and experiential opportunities that enabled them to develop skills in the management of information technology. Twenty-one students participated in this qualitative study. Individual interviews were used to develop insights into student perceptions. Thematic analysis enabled refined themes to emerge. These themes formed the basis of focus group discussions. Focus groups were used to enhance and validate the information from one-to-one interviews by using group dynamics to add experiential richness to the data. Four major themes emerged: computer confidence, flexibility, active learning and practicalities of teaching. The integration of information technology into nursing education requires a dramatic change in thinking. The 'learning curve' is steep for both student and educator and there are many issues that need to be considered. This research does not aim to provide solutions to the issues highlighted but rather offers recommendations for enhancing the teaching and learning experience.


Preventing Diabetes Distress in Adolescents With Type 1 Diabetes: Results 1 Year After Participation in the STePS Program.
The aim is to report 1-year outcomes of the Supporting Teens Problem Solving (STePS) study, a randomized controlled trial comparing a distress and depression prevention program with a diabetes education program for adolescents with type 1 diabetes. With 264 adolescents in two locations (Chicago and San Francisco Bay Area), a randomized controlled trial was conducted comparing the Penn Resilience Program for type 1 diabetes (PRP T1D) to Advanced Diabetes Education. Interventions lasted 4.5 months, and assessments were conducted at baseline, and 4.5, 8, 12, and 16 months. Outcomes of interest were diabetes distress (DD), depressive symptoms, resilience, diabetes self-management, and glycemic control. Latent growth curve modeling was used to test between-group differences over time. Results indicate that there was acceptable randomization and exposure to interventions, and that exposure to PRP T1D was associated with substantial reductions in DD. In addition, stable glycemic control, resilience characteristics, and depressive symptoms were observed 1 year post-treatment. Diabetes management deteriorated in both groups. Intervening before symptoms of psychological distress start can prevent the development of the DD commonly seen in adolescents with type 1 diabetes. The STePS program represents a promising prevention program, and future reports on 2- and 3-year outcomes will explore benefits over longer periods of time.


Selective immediate hypersensitivity to cefepime.
Cefepime is a fourth-generation cephalosporin with a broad antimicrobial spectrum and good activity against both gram-positive and gram-negative organisms. We present the case of a 61-year-old man who developed an immediate urticarial reaction after receiving a single dose of cefepime. Skin tests were positive to cefepime and negative to the other beta-lactam antibiotics. Controlled administration of amoxicillin-clavulanic acid and ceftazidime was well tolerated by the patient. To the best of our knowledge, this is the first report of selective hypersensitivity to cefepime demonstrated by skin and challenge tests. Complete allergological studies, including challenge tests with other beta-lactam antibiotics that produce a negative result in skin tests, should be considered in these patients.


Trends of Bloodstream Infections in a University Greek Hospital during a Three-Year Period: Incidence of Multidrug-Resistant Bacteria and Seasonality in Gram-negative Predominance.
The aim of the study was to assess the epidemiology, the incidence of multidrug-resistant bacteria and bloodstream infections' (BSIs) seasonality in a university hospital. This retrospective study was carried out in the University General Hospital of Patras, Greece, during 2011-13 y. Blood cultures from patients with clinical presentation suggestive of bloodstream infection were performed by the BacT/ALERT System. Isolates were identified by Vitek 2 Advanced Expert System. Antibiotic susceptibility testing was performed by the disk diffusion method and E-test. Resistance genes (mecA in staphylococci; vanA/vanB/vanC in enterococci; blaKPC/blaVIM/blaNDM in Klebsiella spp.) were detected by PCR. In total, 4607 (9.7%) blood cultures were positive from 47451 sets sent to Department of Microbiology, representing 1732 BSIs. Gram-negative bacteria (52.3%) were the most commonly isolated, followed by Gram-positive (39.5%), fungi (6.6%) and anaerobes bacteria (1.8%). The highest contamination rate was observed among Gram-positive bacteria (42.3%). Among 330 CNS and 150 Staphylococcus aureus, 281 (85.2%) and 60 (40.0%) were mecA-positive, respectively. From 113 enterococci, eight were vanA, two vanB and two vanC-positives. Of the total 207 carbapenem-resistant Klebsiella pneumoniae (73.4%), 202 carried blaKPC, four blaKPC and blaVIM and one blaVIM. A significant increase in monthly BSIs' incidence was shown (R2: 0.449), which may be attributed to a rise of Gram-positive BSIs (R2: 0.337). Gram-positive BSIs were less frequent in spring (P < 0.001), summer (P < 0.001), and autumn (P < 0.001), as compared to winter months, while Gram-negative bacteria (P < 0.001) and fungi (P < 0.001) were more frequent in summer months. BSIs due to methicillin resistant S. aureus and carbapenem-resistant Gram-negative bacteria increased during the study period. The increasing incidence of BSIs can be attributed to an increase of Gram-positive BSI incidence, even though Gram-negative bacteria remained the predominant ones. Seasonality may play a role in the predominance of Gram-negative's BSI.


Linear piezoresistive strain sensor based on graphene/g-C3N4/PDMS heterostructure.
Here we report a novel hybrid material consists of 2D graphitic carbon nitride (g-C3N4) and graphene heterostructure that exhibits piezoresistivity superior to graphene and potentially being used as a strain sensor. The g-C3N4 that contains periodically spaced triangular nanopores is used for improving the piezoresistivity of the sensor imparting change in the polarization upon application of strain. In this work, we have investigated graphene/g-C3N4 interfaced materials and quantified its piezoresistive effects through experimental analysis and density functional theory (DFT) based computational studies provide insights into the electronic structures of the hybrid interfaces. We have observed a linear response in electrical resistance for a wide range of uniaxial strains up to ∼25%. The observed increase in resistance upon application of strain corroborates with our computational finding of strain-dependent band gap opening. Further, it has been realized that band-gap opening occurs exclusively in the graphitic layer of the composite materials under strain. However, the g-C3N4 bands remain intact at the interface. The linearity and a considerably small gauge factor (1.89) make graphene/g-C3N4 a promising heterostructure material unlike conventional metal gauge sensor in wide strain pressure sensor devices.


Down-regulation of CD20 on B cells upon CD40 activation.
CD20 is a B cell-specific surface antigen that is thought to play an important role in B cell activation and proliferation, possibly by functioning as a calcium channel or interacting with other cell surface molecules important in B cell signal transduction, such as CD40. In this study, it was found that stimulation through CD40 caused a dramatic decrease in the expression of surface CD20 in normal human B lymphocytes. Down-regulation of CD20 was time and ligand concentration dependent, beginning as early as 15 min after incubation with CD40 ligand-transfected fibroblasts. The rapid onset of this effect in the presence of stable steady-state mRNA levels suggests that CD20 down-regulation occurs at a nontranscriptional level. Confocal fluorescent microscopy indicates that CD20 and CD40 are internalized upon CD40 activation. Specifically, CD20 translocates into lipid rafts and is internalized into cytoplasmic vesicles, in a process that is inhibited by cytochalasin B and protein kinase C antagonists. Paradoxically, one functional consequence of CD20 down-regulation was enhanced calcium signaling upon CD20 cross-linking. These observations support the notion that CD20 engages downstream signaling pathways that alter calcium homeostasis rather than functioning as a calcium channel itself, such signal transduction is enhanced upon CD20 internalization, and CD40 is a regulator of CD20-mediated signaling.


Biosurfactants: A Covid-19 Perspective.
The recent outbreak in severe acute respiratory syndrome - coronavirus-2 (SARS-CoV-2) has demonstrated the complete inability of nations across the world to cope with the pressures of a global pandemic, especially one in which the only current feasible treatments are those which deal with the symptoms alone and not the viral cause. As the death toll rises, scientists begin to fall toward new avenues of research, with novelty showing itself to be an incredible and so far, underrated resource. In this case, the use of biosurfactants in dealing with this pandemic justifies extensive study with their potential applications being in the prevention of viral spread; dealing with the symptoms that develop after the incubation period; directly targeting viral infected cells and preventing the spread of the virus throughout the host, all in addition to also acting as potential drug delivery systems and cleaning agents. This extensive avenue of biosurfactants owes to the simplicity in their amphiphilic structure which permits them to interact directly with the lipid membrane of the coronavirus, in a way which wouldn't be of significant threat to the host. Although it could possibly interact and affect the virus, it could also affect human internal organs/cells by interacting with lipid membrane, if (biosurfactant is) ingested, and it still needs further studies in human models. The structure of the coronavirus, in this case SARS-CoV-2, is detrimentally dependent on the integrity of its lipid membrane which encloses its vital proteins and RNA. Biosurfactants possess the innate ability to threaten this membrane, a result of their own hydrophobic domains across their amphiphilic structure. With biosurfactants additionally being both natural and sustainable, while also possessing a remarkably low cytotoxicity, it is of no doubt that they are going to be of increasing significance in dealing with the current pandemic.


Intraoperative tap test for coronal syndesmotic instability: A cadaveric study.
Precise diagnosis of distal tibiofibular syndesmotic injury is challenging, and a gold standard diagnostic test has still not been established. Tibiofibular clear space identified on radiographic imaging is considered the most reliable indicator of the injury. The Cotton test is the most widely used intraoperative technique to evaluate the syndesmotic integrity although it has its limitations. We advocate for a novel intra operative test using a 3.5 mm blunt cortical tap. Tibiofibular clear space was assessed in nine cadaveric specimens using three sequential fluoroscopic images. The first image was taken prior to the application of the tap test (intact, non-stressed). Then, a 2.5 mm hole was drilled distally on the lateral fibula, and a 3.5 mm cortical tap was then threaded in the hole. The tap test involved gradually advancing the blunt tip against the lateral tibia, providing a tibiofibular separation force (intact, stressed). This same stress was then applied after all syndesmotic ligaments were released (injured, stressed). Measurements were compared by one-way ANOVA and paired Student's t-test. Intra and inter-observer agreements were evaluated by intraclass correlation coefficient (ICC). P-values <.05 were considered significant. We found excellent intra-observer (0.97) and inter-observer (0.98) agreement following the imaging assessment. Significant differences were found in the paired comparison between the groups (p < .05). When using an absolute value for TFCS >6 mm as diagnostic for coronal syndesmotic instability, the tap test demonstrated a 96.3% sensitivity and specificity, a 96.3% PPV and NPV and a 96.3% accuracy in diagnosing coronal syndesmotic instability. Our cadaveric study demonstrated that this novel coronal syndesmotic instability test using a 3.5 mm blunt cortical tap is a simple, accurate and reliable technique able to demonstrate significant differences in the tibiofibular clear space when injury was present. It could represent a more controlled and stable alternative to the most used Cotton test.


Melittin Increases Cisplatin Sensitivity and Kills KM-H2 and L-428 Hodgkin Lymphoma Cells.
Hodgkin lymphoma (HL) is neoplasia with high cure rates. However, not all patients can be cured with the current treatment. Chemo-resistance of tumor cells is one factor involved in treatment failure. In addition to its pore-forming activity on lipid bilayer membranes, the toxin melittin from bee venom is an inhibitor of several cancer-related signaling pathways. Moreover, melittin analogs have been shown to inhibit the activity of ATP binding cassette (ABC) transporters which are known to play important roles in the chemo-resistance of tumor cells. Therefore, we tested the toxicity of melittin for HL cell lines KM-H2 and L-428 and whether melittin can increase the chemo-sensitivity of cisplatin-resistant HL cells. We found high toxicity of melittin for KM-H2 and L-428 cells. In co-cultures with normal blood cells, melittin preferentially killed KM-H2 and L-428 cells. In addition, we observed increased cisplatin sensitivity of chemo-resistant L-428 cells after treatment with melittin. ABC transporter activity was not reduced after treatment with melittin. Our data suggest that melittin or melittin analogs might be promising agents for the future development of treatment strategies for HL patients with resistant disease.


Carbonic acid: an important intermediate in the surface chemistry of calcium carbonate.
Calcium carbonate is an important and ubiquitous component of biological and geochemical systems. In this study, the surface chemistry of calcium carbonate with several trace atmospheric gases including HNO3, SO2, HCOOH, and CH3COOH is investigated with infrared spectroscopy. Adsorbed carbonic acid, H2CO3, is found to be an intermediate in these reactions. In the absence of adsorbed water, carbonic acid is stable on the surface at room temperature. However, upon water adsorption, carbonic acid dissociates as indicated by the evolution of gaseous CO2 and the disappearance of infrared absorption bands associated with adsorbed carbonic acid. Thus, it is postulated that under ambient conditions, carbonic acid may be an important albeit short-lived intermediate in the surface chemistry of calcium carbonate.


Phase I trial of panobinostat in children with diffuse intrinsic pontine glioma: A report from the Pediatric Brain Tumor Consortium (PBTC-047).
Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood cancer with median survival of less than 1 year. Panobinostat is an oral multihistone deacetylase inhibitor with preclinical activity in DIPG models. Study objectives were to determine safety, tolerability, maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics of panobinostat in children with DIPG. In stratum 1, panobinostat was administered 3 days per week for 3 weeks on, 1 week off to children with progressive DIPG, with dose escalation following a two-stage continual reassessment method. After this MTD was determined, the study was amended to evaluate the MTD in children with nonprogressive DIPG/Diffuse midline glioma (DMG) (stratum 2) on an alternate schedule, 3 days a week every other week in an effort to escalate the dose. For stratum 1, 19 subjects enrolled with 17/19 evaluable for dose-finding. The MTD was 10 mg/m2/dose. Dose-limiting toxicities included thrombocytopenia and neutropenia. Posterior reversible encephalopathy syndrome was reported in 1 patient. For stratum 2, 34 eligible subjects enrolled with 29/34 evaluable for dose finding. The MTD on this schedule was 22 mg/m2/dose. DLTs included thrombocytopenia, neutropenia, neutropenia with grade 4 thrombocytopenia, prolonged intolerable nausea, and increased ALT. The MTD of panobinostat is 10 mg/m2/dose administered 3 times per week for 3 weeks on/1 week off in children with progressive DIPG/DMG and 22 mg/m2/dose administered 3 times per week for 1 week on/1 week off when administered in a similar population preprogression. The most common toxicity for both schedules was myelosuppression.


SLE: management overview.
Patients with systemic lupus erythematosus can often benefit from cooperative and collaborative interventions prescribed by both physicians and other arthritis health care professionals.


H3K9 and H4K20 methyltransferases are directly involved in the heterochromatinization of the paternal chromosomes in male Planococcus citri embryos.
Using a new method for bulk preparation of early stage embryos, we have investigated the role played by putative Planococcus citri H3K9 and H4K20 histone methyl transferases (HMTases) in regulating heterochromatinization of the imprinted paternal chromosomal set in male embryos. We found that H3K9 and H420 HMTases are required for heterochromatinization of the paternal chromosomes. We present evidence that both HMTases maintain the paternal "imprint" during the cleavage divisions when both parental chromosome sets are euchromatic. A testable model that accommodates our findings is proposed.


[Sex hormone receptors in the gastric mucosa in gastric precancer and cancer].
Sex hormones receptors from 240 patients with stomach cancer and precancer were studied using an immunoperoxidase method. Reception of steroid hormones was shown to influence stomach cancer development while the "perversion" of this reaction may determine unfavourable prognosis.


Effect of chemoprophylaxis with an ivermectin sustained-release bolus on acquired resistance to gastrointestinal parasites in cattle.
The influence of chemoprophylaxis with an ivermectin sustained-release bolus in the first grazing season on the resistance of cattle to gastrointestinal nematodes during the following grazing season was investigated. In 1993 and 1994 dairy replacement calves were either given one bolus at the start of their first grazing season or left untreated. The two groups were grazed separately on a pasture that was divided into two similar sized paddocks. Faecal egg counts, serum pepsinogen and antibody levels were measured to evaluate host-parasite contact. Pasture infection levels were estimated by pasture larval counts and worm counts in tracer calves. After winter housing the animals were monitored during their second grazing season on a pasture that was also divided into two similar sized paddocks. Acquired resistance to gastrointestinal nematodes was evaluated by faecal egg counts and weight gains. Again, pasture infection levels were determined and pepsinogen and antibody levels were measured. During the first grazing seasons gastrointestinal nematode infections were controlled very effectively by the bolus, as shown by the greater weight gains, the negligible faecal egg counts and the low serum pepsinogen and antibody levels in the treated calves. In contrast, all parameters showed extensive parasite-host contact in the untreated animals. The efficient prophylaxis in the treated groups resulted in low levels of larval contamination on the paddocks grazed by the treated animals, compared to moderate infection levels at the end of both first grazing seasons on the paddocks grazed by the untreated animals. During the second grazing seasons (1994 and 1995) the faecal egg output was low in all groups. Although in the previously treated animals faecal egg counts were consistently higher, the differences were minimal, resulting in comparable levels of larval contamination on both paddocks. Serum pepsinogen and antibody levels were not significantly different between the groups and indicated a similar level of larval uptake on both paddocks. No negative effect of the previous chemoprophylaxis on the clinical condition and the weight gain of the second season grazing animals was observed.


Catatonia in Adolescence: First Onset Psychosis or Anti-NMDAr Encephalitis?
Catatonia is a rare condition that can occur in developmental disorders, but it is more frequently seen in schizophrenia. Recently, a high prevalence of cerebrospinal fluid abnormalities including the detection of antineuronal autoantibodies has been observed in psychotic patients. Among these autoimmune encephalopathies associated with a psychiatric condition, a great deal of attention has been paid to anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis, which may present, among other things, symptoms such as catatonia, which therefore imposes a differential diagnosis with respect to the early psychosis. The aim of our study was to describe the clinical characteristics of 4 cases with catatonic symptoms to understand the differences between the psychotic symptoms due to a type of encephalitis anti-NMDAr and the psychotic symptoms without anti-NMDAr.


PEDAGOGICAL ASPECTS OF THE IMPACT OF SMOKING ON THE HUMAN BODY BASED ON RADIOGRAPHIC DENSITY INDICATORS OF MAXILLARY SINUS BONE WALLS.
The most effective process of quitting smoking can be achieved through precise and complete identification of the adverse effects on the human body. The aim was to examine the influence of smoking on the density of the walls of the paranasal sinuses. 80 individuals of the young age and both genders were included into the research. Depending on the presence of pathological changes in the sinuses and smoking habits, all participants were divided into four groups. It was found that in the group of smokers without any paranasal sinus pathology, the density is 2.66% lower than the intact group. This figure is significantly higher in patients suffering from rhinosinusitis but not smoking, where it is 45.18%. The maximum difference from the control group is observed in individuals suffering from chronic rhinosinusitis and being smokers, with a difference of 81.03%. Pedagogical aspects of the impact of smoking on the human body based on radiographic density indicators of maxillary sinus bone walls were detected. It has been observed that smoking can exacerbate the negative impact of inflammatory processes in the paranasal sinuses.


Pregnancy smoking in context: the influence of multiple levels of stress.
Pregnancy smoking remains a major public health concern in the United States. Approximately 10.2% of women smoke during pregnancy, placing their offspring at increased risk for adverse perinatal and childhood outcomes. However, little is known about contextual influences on pregnancy smoking. This study examines the intimate social context, broader social context, and socioeconomic context as predictors of smoking in a sample of 113 pregnant women (M (age) = 29.7 years; 90.3% White, non-Hispanic). We developed latent variables at each contextual level comprising indicators of stress and resources measured during the first and second trimesters, to serve as predictors of both persistent pregnancy smoking and smoking intensity during the third trimester in a single comprehensive structural equation model. Results indicate that stressful socioeconomic context was positively associated with the probability of being a persistent pregnancy smoker (probit regression coefficient = .70, p<.05). Broader social context was the only significant predictor of smoking rate, with greater stress and fewer resources associated with a greater number of cigarettes smoked during the third trimester (standardized regression coefficient = .81, p<.05). Results suggest that pregnancy smoking is a complex phenomenon that may be influenced by psychosocial context at multiple levels. Elucidating mechanisms by which contextual influences affect pregnant women's smoking patterns may inform smoking cessation and reduction interventions with this population.


Porphyromonas gingivalis lipopolysaccharide-stimulated bone resorption via CD14 is inhibited by broad-spectrum antibiotics.
In the present study, we examined mechanisms of Porphyromonas gingivalis lipopolysaccharide (P-LPS)-stimulated bone resorption via CD14, one of the lipopolysaccharide (LPS) receptors, and also assessed the inhibitory action of several kinds of antibiotics on the LPS-induced stimulation. First, we observed by using mouse embryonic calvarial cells that P-LPS stimulated bone resorption through the action of endogenous interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) via CD14 because (i) P-LPS-stimulated expression of IL-1beta and IL-6 genes in calvarial cells was inhibited by an anti-mouse CD14 antibody, (ii) stimulated bone resorption was markedly inhibited by both IL-1beta and IL-6 antibodies, and (iii) P-LPS-stimulated bone resorption was clearly neutralized by an anti-mouse CD14 antibody. Next, we examined the effects of several kinds of antibiotics on P-LPS-stimulated bone resorption via CD14. Two of them, chloramphenicol and erythromycin, inhibited P-LPS-stimulated bone resorption in a dose-dependent manner. In an additional experiment, we observed that chloramphenicol clearly inhibited P-LPS-stimulated expression of the CD14, IL-1beta, and IL-6 genes in calvarial cells. These results suggest that chloramphenicol might be a useful antibiotic as an anti-inflammatory agent against P-LPS-stimulated periodontal destruction occurring via CD14 in periodontal disease.


Contribution of ABCC4-mediated gastric transport to the absorption and efficacy of dasatinib.
Several oral multikinase inhibitors are known to interact in vitro with the human ATP-binding cassette transporter ABCC4 (MRP4), but the in vivo relevance of this interaction remains poorly understood. We hypothesized that host ABCC4 activity may influence the pharmacokinetic profile of dasatinib and subsequently affect its antitumor properties. Transport of dasatinib was studied in cells transfected with human ABCC4 or the ortholog mouse transporter, Abcc4. Pharmacokinetic studies were done in wild-type and Abcc4-null mice. The influence of Abcc4 deficiency on dasatinib efficacy was evaluated in a model of Ph(+) acute lymphoblastic leukemia by injection of luciferase-positive, p185(BCR-ABL)-expressing Arf(-/-) pre-B cells. Dasatinib accumulation was significantly changed in cells overexpressing ABCC4 or Abcc4 compared with control cells (P < 0.001). Deficiency of Abcc4 in vivo was associated with a 1.75-fold decrease in systemic exposure to oral dasatinib, but had no influence on the pharmacokinetics of intravenous dasatinib. Abcc4 was found to be highly expressed in the stomach, and dasatinib efflux from isolated mouse stomachs ex vivo was impaired by Abcc4 deficiency (P < 0.01), without any detectable changes in gastric pH. Abcc4-null mice receiving dasatinib had an increase in leukemic burden, based on bioluminescence imaging, and decreased overall survival compared with wild-type mice (P = 0.048). This study suggests that Abcc4 in the stomach facilitates the oral absorption of dasatinib, and it possibly plays a similar role for other orally administered substrates, such as acetylsalicylic acid. This phenomenon also provides a mechanistic explanation for the malabsorption of certain drugs following gastric resection.