[Return-to-Work - The Transition after Psychiatric Inpatient Treatment].
Workers on sick-leave due to a mental illness have enormous problems to return to work. The main objective of the present study is to examine, how individuals experience the transition from the mental health system to their workplace. A qualitative research design guided by a grounded theory approach was used. Narrative interviews with ten workers on sick leave and four semi-structured interviews with return-to-work-experts were conducted. Relevant for returning to work is the interplay between the involved persons. Essential is the interpretation of the transition and as a result, which calls for action are made to the participants. Clinical interventions for returning to work should focus the support on the expectations of the participants and stimulate a common interpretation.


Effect of radial high-speed ultrasonic vibration cutting on machining performance during finish turning of hardened steel.
Hardened steel has been widely used in the aviation and automotive fields owing to its unique properties. However, the poor machining performance for finishing hardened steel owing to low attainable cutting speeds and rapid tool wear has become a bottleneck in the functional performance and range of applications. In this study, a radial high-speed ultrasonic vibration cutting (R-HUVC) process was adopted for improving the machining performance of finishing hardened steel. R-HUVC involves the use of radial ultrasonic vibrations which ensure the separation of the tool and workpiece. The kinematics of R-HUVC were analyzed through a theoretical model, and its surface generation mechanisms in the intermittent cutting mode were studied. Then, finish turning experiments were conducted on the cutting force, surface roughness, and tool life to validate its machining performance compared to that of conventional cutting (CC) for a wide range of finishing conditions. The experimental results showed that R-HUVC can realize a lower cutting force, longer tool life, and better surface roughness compared to CC. It was verified that R-HUVC can be applied to high-speed machining for the finish turning of hardened steel because it improves the machining performance.


Multicompartment pharmacokinetic analysis and simulations using a programmable calculator.
This paper describes the use of a programmable calculator (HP-97), for fitting plasma concentration profiles to 1 and 2 compartment open models and calculating fitted and derived parameters together with estimates of steady state plasma drug levels following various dosage regimens in clinical settings.


Interaction of deformable solid and hollow particles with rough surface morphology in colloidal systems.
A majority of natural particles have deformable and rough surfaces. Past research indicated a lack of information for a numerical model to simulate the potential non-contact interaction between two deformable particles with uneven surfaces. The simulation of deformable particles is critical to better understanding the interaction of deformable particles in colloidal systems. We hypothesized that numerical models could simulate the deformation process of solid and hollow particles, and the constructed models could predict the impact of deformation on the interaction of rough-surfaced solid or hollow deformable particles. This work modeled the deformable solid and hollow particles with rough surface morphologies following a fractal geometry theory. Their non-contact interaction was simulated following the three-stages deformation model. Also, the impacts of surface tension, particle size, and surface roughness on the interaction of the particles were investigated. It was observed that the total potential energy of deformable solid and hollow particles followed a similar pattern under different conditions. The difference in the energy profile between solid and hollow particles is that the hollow particles generate a deeper primary minimum, and the energy barrier disappears, indicating that the hollow particles have better attachment affinity. The results show that the increased particle size will strengthen the deformability of deformable solid and hollow particles and their potential interaction, and particle size will be the most influential parameter in affecting the deformability of particles. When the particle size increased from 10 nm to 1000 nm, the deformation region of solid particles was enlarged from 5 nm to 90 nm. Nevertheless, increased surface tension would weaken the deformability of deformable solid and hollow particles, which would significantly reduce particle aggregation. The increase in the fractal dimension would reduce solid and hollow particles' deformability but increase the potential interaction energy. The controversial results could be found by increasing fractal roughness, which would improve the deformability of particles and reduce the interaction energy. The results of this study could be applied for foreseeing the deformation and interaction of deformable particles with potential applications in suspension systems, such as biological cell suspensions.


Fusiform P1 segment artery aneurysm in a pediatric patient: technical case report.
We present an unusual aneurysm in a pediatric patient. Due to the fusiform nature of the aneurysm and the small size of the patient, a unique surgical solution was applied. One year of clinical follow-up is also provided.


Snatching the Crown from SARS-CoV-2.
In this issue of Cell Host & Microbe, three papers describe the pseudotyping of vesicular stomatitis virus (VSV) with the SARS-CoV-2 spike. This VSV-CoV-2-S platform allows virus neutralization assays to be performed at BSL-2 and also has applications as a candidate vectored vaccine to elicit protective immunity against SARS-CoV-2.


Narrowing of the dental pulp chamber in patients with renal diseases.
Narrowing of the dental pulp chamber was studied radiologically in fifty one patients with renal diseases. Two thirds of the patients were suffering from terminal uremia and were treated either by renal transplantation or with hemodialysis. The remaining patients were nonuremic and were treated with immunosuppressants because of progressive renal disease. There were significantly more patients with narrowing of the dental pulp chamber among the transplant patients than among the other patients. The transplantations included the use of higher doses of corticosteroids than the other treatments. As the median dose of corticosteroids was higher and total plasma steroid clearance was lower in the patients with narrowing of the dental pulp chamber than in the other patients, the amount of this drug received and its pharmacokinetics seemed to be an essential factor in the initiation of narrowing of the dental pulp chamber.


Hepatic artery administration of degradable starch microspheres: II. Effects on incorporation of uridine and uracil into RNA of an adenocarcinoma transplanted to rat liver.
Effects of degradable starch microspheres administered via the hepatic artery were examined in rats in which an adenocarcinoma was transplanted into the liver. 3H-uridine or 3H-uracil with cold uridine and uracil, respectively, in amounts corresponding to therapeutic doses of these two pyrimidines as fluoro compounds, were administered with or without microspheres. Labeling of the acid-soluble fraction and RNA of tumor, liver, small intestine, spleen, kidney, and bone marrow was examined after 3 and 60 min after injection. When microspheres were added, the specific radioactivity of tumor RNA was significantly higher at both 3 min (P less than 0.05) and 60 min (P less than 0.01) in the rats given uridine, and in rats given uracil it was higher at 60 min after injection (P less than 0.05). There were no such differences in the labeling of the normal tissues. The results indicate that arterial administration of cytostatic drugs, such as 5-fluoropyrimidines, together with degradable starch microspheres might increase the cytotoxic effect on tumors nourished by the artery.


T-cell tracking, safety, and effect of low-dose donor memory T-cell infusions after αβ T cell-depleted hematopoietic stem cell transplantation.
The delayed recovery of adaptive immunity underlies transplant-related mortality (TRM) after αβ T cell-depleted hematopoietic stem cell transplantation (HSCT). We tested the use of low-dose memory donor lymphocyte infusions (mDLIs) after engraftment of αβ T cell-depleted grafts.A cohort of 131 pediatric patients (median age 9 years) were grafted with αβ T cell-depleted products from either haplo (n = 79) or unrelated donors (n = 52). After engraftment, patients received mDLIs prepared by CD45RA depletion. Cell dose was escalated monthly from 25 × 103 to 100 × 103/kg (haplo) and from 100 × 103 to 300 × 103 /kg (MUD). In a subcohort of 16 patients, T-cell receptor (TCR) repertoire profiling with deep sequencing was used to track T-cell clones and to evaluate the contribution of mDLI to the immune repertoire.In total, 343 mDLIs were administered. The cumulative incidence (CI) of grades II and III de novo acute graft-versus-host disease (aGVHD) was 5% and 2%, respectively, and the CI of chronic graft-versus-host disease was 7%. Half of the patients with undetectable CMV-specific T cells before mDLI recovered CMV-specific T cells. TCR repertoire profiling confirmed that mDLI-derived T cells significantly contribute to the TCR repertoire up to 1 year after HSCT and include persistent, CMV-specific T-cell clones.


[Uterine rupture during second trimester abortion induced with misoprostol].
A 27-year-old woman with one prior cesarean section and one vaginal delivery was seen with a request for termination of pregnancy in her 17th week of pregnancy. Using vaginal misoprostol for two days the vaginal delivery failed. The fetus was giving way of previous scar resulting in rupture of the uterus, loss of blood and suture of uterus by laparotomy.


Goals, preferences, and concerns of patients with acute myeloid leukemia at time of treatment decision.
Current cancer value-based models require documentation of patient goals of care and an evidence-based treatment course commensurate with patient goals. This feasibility study assessed the utility of an electronic tablet-based questionnaire to elicit patient goals, preferences, and concerns at a treatment decision making time point in patients with acute myeloid leukemia. Seventy-seven patients were recruited from three institutions prior to seeing the physician for treatment decision-making visit. Questionnaires included demographics, patient beliefs, and decision-making preferences. Analyses included standard descriptive statistics appropriate for the level of measurement. Median age was 71 (range = 61-88), 64.9% female, 87.0% white, and 48.6% college educated. On average, patients completed the surveys unassisted in 16.24 min and providers reviewed the dashboard in 3.5 min. All but one patient completed the survey prior to starting treatment (98.7%). Providers reviewed the survey results prior to seeing the patient 97.4% of the time. When asked their goals of care, 57 (74.0%) patients agreed with the statement "my cancer is curable" and 75 (97.4%) agreed that the treatment goal was to get rid of all cancer. Seventy-seven (100%) agreed the goal of care is to feel better and 76 (98.7%) agreed the goal of care is live longer. Forty-one (53.9%) indicated they wanted to make treatment decisions together with the provider. The top two concerns were understanding treatment options (n = 24; 31.2%) and making the right decision (n = 22; 28.6%). This pilot demonstrated the feasibility of using technology for decision-making at the point of care. Eliciting patient goals of care, treatment outcomes expectations, decision-making preferences, and top concerns may provide clinicians with information to inform the treatment discussion. A simple electronic tool may provide valuable insight into patient understanding of disease to better tailor patient-provider discussion and treatment decision-making.


Maternal obesity is not associated with placental lipid accumulation in women with high omega-3 fatty acid levels.
Placentas of obese women have higher lipid content compared to lean women. We have previously shown that supplementation of overweight and obese women with omega-3 fatty acids decreases placental esterification pathways and total lipid content in a mid-western population (Ohio). We hypothesized that placental lipid accumulation and inflammation would be similar between lean and obese women living in a region of high omega-3 intake, such as Hawaii. Fifty-five healthy, normal glucose tolerant women from Honolulu Hawaii, dichotomized based on pre-pregnancy BMI into lean (BMI <25 kg/m2, n = 29) and obese (BMI >30 kg/m2, n = 26), were recruited at scheduled term cesarean delivery. Maternal plasma DHA levels were analyzed by mass spectrometry. Expression of key genes involved in fatty acid oxidation and esterification were measured in placental tissue using qPCR. Total lipids were extracted from placental tissue via the Folch method. TNF-α concentration was measured by enzyme-linked immunosorbent assay in placental lysates. DHA levels were higher in lean women compared to obese women (P = 0.02). However, DHA levels in obese women in Hawaii were eight times higher compared to obese Ohioan women (P=<0.0001). Placental lipid content and expression of key genes involved in fatty acid oxidation and esterification were similar (P > 0.05) between lean and obese women in Hawaii. Furthermore, TNF-α placental lysates were not different between lean and obese women. Though obese women in Hawaii have lower DHA levels compared to their lean counterparts, these levels remain over eight times as high as obese Ohioan women. These relatively high plasma omega-3 levels in obese women in Hawaii may suppress placental lipid esterification/storage and inflammation to the same levels of lean women, as seen previously in vitro.


Playfulness and Interaction: An Exploratory Study of Past and Current Exposure to Domestic Violence.
Violence against women affects mother-child interactions, which may in turn affect their children's playfulness. We examined the effect of a history of violence against mothers on mother-child interactions and children's playfulness. This cross-sectional pilot study consisted of 36 mother-child dyads residing in family crisis shelters due to serious violence from an intimate partner. One subgroup had experienced violence during childhood, another had posttraumatic stress disorder (PTSD). Instruments included Posttraumatic Diagnostic Scale, Test of Playfulness, and Coding Interactive Behavior System. Mann-Whitney test and Spearman's rank correlation coefficients were calculated. Results indicated that children of mothers without PTSD were more playful than children of mothers with PTSD. Mothers who had not reported of childhood exposure to violence and who did not have PTSD had better interactions with more playful children.


35 mM K(+)-stimulated 45Ca2+ uptake in cerebellar granule cell cultures mainly results from NMDA receptor activation.
In primary cultures of cerebellar granule cells, the Ca2+ influx resulting from K+ depolarization (35 mM) was equal to one-third of that observed with 100 microM N-methyl-D-aspartate (NMDA) and was reduced in a major part (90%) by NMDA receptor antagonists. The rank order of potency of these competitive and non-competitive NMDA receptor antagonists was very close to their affinity for the NMDA and phencyclidine sites respectively. Granular cell depolarization with 35 mM K+ also induced a large increase in the extracellular glutamate concentration. Repeated washes of the culture wells, addition of glutamate pyruvate transaminase (+2 mM pyruvate), or pretreatment of the cells with tetanus toxin resulted in a parallel reduction of the extracellular glutamate concentration and 45Ca2+ uptake measured after a 35 mM K+ stimulation. Dihydropyridine (BAY K-8644) stimulated the release of glutamate in a nifedipine-sensitive manner in the presence of 15 mM K+. However, nifedipine (1 microM), which decreased by 60% the K(+)-induced 45Ca2+ uptake, did not reduce the 35 mM K(+)-evoked glutamate release. Taken together, these results demonstrated that in cerebellar granule cell cultures, 90% of the 35 mM K(+)-stimulated 45Ca2+ influx resulted from the release of glutamate and the consecutive activation of NMDA receptors. Activation of these glutamate receptors then allows Ca2+ influx to occur through L-type voltage-operated Ca2+ channels.


Monoamines as mediators of the antinociceptive effect of baclofen.
The antinociceptive activity of baclofen was evaluated in rats using the tail flick and hot plate tests. When baclofen was administered intraperitoneally, pretreatment with depletors of monoamines and catecholamines (reserpine, alpha-MPT) produced a marked increase in antinociceptive activity in both tests. Blockade of noradrenergic and dopaminergic receptors with phentolamine, chlorpromazine and haloperidol produced similar increases. These agents were without intrinsic effect in these tests except for alpha-MPT which increased the tail flick latency slightly. Alterations in serotonergic function did not consistently alter the action of baclofen. When baclofen was administered intrathecally, pretreatment with reserpine and alpha-MPT produced minimal alterations in antinociceptive activity. It is likely that interactions between baclofen and monoamines occur at supraspinal sites.


Measures to control blood activation during assisted circulation.
Major improvements in heart assist devices have allowed prolonged mechanical circulatory support with successful subsequent weaning or heart transplantation. The contact of blood with biomaterials used in life-sustaining devices and numerous biomaterial-independent factors elicit a systemic inflammatory response, which involves activation of various plasma protein systems and blood cells. Prolonged mechanical circulatory support elicits a systemic inflammatory response and hemostatic perturbations similar to that reported during cardiopulmonary bypass. However, in the setting of prolonged assistance, time has a complex and ill-known influence on blood activation. Methods to reduce blood activation during prolonged assisted circulation are derived from cardiopulmonary bypass investigations. Improving the biocompatibility of artificial devices can be achieved either by biomaterial surface modifications, by inhibition of biologic cascades leading to blood activation, or by controlling end points of biologic cascades. However, the necessity to respect the integrity of the organism during prolonged assistance precludes most systemic interventions and limits the control of blood activation to the area of the device.


Obstructive sleep apnea and pregnancy: the effect on perinatal outcomes.
Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper airway obstruction, resulting in hypoxemia, hypercapnia and sleep fragmentation. Pathophysiological sequelae include sympathetic activation, increased oxidative stress and a generalized inflammatory response, culminating in endothelial dysfunction. These are the proposed mechanisms that mediate the increased risk of hypertension and cardiovascular disease among patients with OSA outside of pregnancy. It is intriguing to consider the consequences of these events on pregnancy outcomes. There is a growing literature on the impact of maternal OSA on hypertensive disorders of pregnancy, gestational diabetes and impaired fetal growth. The data, while promising, require confirmation with larger numbers to verify the findings. OSA may be an important mediator of the poor perinatal outcomes associated with maternal obesity; moreover, one which may be amenable to treatment. This review discusses OSA and summarizes the current literature linking OSA with adverse perinatal outcomes.


Density of outdoor advertising of consumable products in NYC by neighborhood poverty level.
To determine if outdoor advertising density for non-alcoholic drinks, food, tobacco products, and alcohol, is associated with neighborhood poverty or other Census-level characteristics in New York City (NYC). From June - July of 2015, photographs were taken of all street-level, stationary outdoor advertising (posters, stickers, decals, etc.) for consumable products in a sample of 953 NYC retail-dense street segments. Density of product images was analyzed by neighborhood poverty level and other characteristics using multivariate negative-binomial regression. A total of 16,305 discrete advertisements displaying 50,673 product images were photographed. Total product image prevalence relative to retail density was not significantly higher in high- vs. low-poverty neighborhoods, as hypothesized (OR: 1.31; 95% CI: 0.98, 1.77). However, total product image prevalence was higher in neighborhoods with a higher percentage of Black residents (OR: 1.08; 95% CI: 1.04, 1.12), and for sugary drinks in areas with a higher percentage of adults with <HS diploma (OR: 1.32; 95% CI: 1.11, 1.58). Product images were abundant throughout NYC's retail-dense areas, with marginally greater prevalence by some Census-level demographics, irrespective of the content displayed.


Neodymium:YAG laser ablation of posterior urethral valves.
We report successful neodymium:YAG laser ablation of posterior urethral valves in 6 boys. No strictures or incontinence resulted.


The Role of Green Gram Plant Volatile Blends in the Behavior of Arctiid Moth, Spilosoma obliqua.
This study investigated effects of volatile blends released from undamaged (UD), insect-damaged [ID, plants fed by larvae of Spilosoma obliqua Walker (Lepidoptera: Arctiidae)] and mechanically-damaged (MD) plants of three green gram cultivars [PDM 54, Pusa Baisakhi and Samrat] including synthetic blends on the behavior of conspecific adult moths in Y-tube olfactometer bioassays. Females showed attraction towards volatile blends of UD, ID and MD plants of these green gram cultivars against the control solvent (CH2Cl2). The components of volatile blends in UD plants of three green gram cultivars are not similar, but no any difference was found among three cultivars in term of the attractive effect on the insect moths when volatile blends from UD plants of these three cultivars were tested against one another. Females were more attracted towards volatile blends of ID plants of a particular cultivar compared to UD plants of the same cultivar. Total amount of volatiles was higher in ID plants than UD plants. Some herbivore-induced plant volatiles - (Z)-3-hexenal, 1-hexanol, (Z)-3-hexenyl acetate, 2-octanol and ocimene were attractive to the insect moths. Females were attracted towards three synthetic blends resembling amounts present in natural volatile blends of ID plants of these three cultivars in Y-tube olfactometer and wind tunnel bioassays, suggesting that involvement of host-specific chemical cues in long-range host location by S. obliqua females. If attraction of adult S. obliqua to these synthetic volatile blends is upheld by field trials then these blends may find practical application in detection and monitoring of S. obliqua populations.


mBAND analysis of chromosome aberrations in lymphocytes exposed in vitro to alpha-particles and gamma-rays.
To investigate the profiles of chromosome damage induced in vitro by exposure to alpha-particles and gamma-rays. Human peripheral blood lymphocytes were exposed to three dose regimes: alpha-particle doses of 0.2 and 0.5 Gy and a gamma-ray dose of 1.5 Gy. After culturing for 47 hours, chromosome aberrations involving the number 5 chromosomes were identified using a multi-coloured banding (mBAND) technique. Analysis of the frequencies of chromosome 5 breaks within aberrant cells and within aberrant number 5 chromosomes demonstrated that alpha-particle irradiation is more likely to result in multiple breaks in a chromosome than gamma-irradiation. Additionally, overdispersion was observed for all doses for the distribution of breaks amongst all cells analysed and breaks amongst total number 5 chromosomes, with this being greatest for the 0.2 Gy alpha-particle dose. The ratio of interchanges to intrachanges (F ratio) was 1.4 and 2.4 for 0.2 and 0.5 Gy alpha-particles respectively and 5.5 for 1.5 Gy gamma-rays. Evaluation of simple versus complex exchanges indicated ratios of 1.9 and 2.7 for 0.2 and 0.5 Gy alpha-particles respectively and 10.6 for 1.5 Gy gamma-rays. The majority of the intrachanges involving chromosomes 5 induced by alpha-particle radiation were associated with more complex exchanges. This study has confirmed that exchanges induced by exposure to high linear energy transfer (LET) alpha-particle radiation comprise a greater proportion of intrachanges than those induced by exposure to low LET gamma-rays. However, since the majority of these are associated with complex rearrangements and likely to be non-transmissible, this limits their applicability as a marker of past in vivo exposure.


Is the risk of small for gestational age influenced by maternal body composition in young Japanese women?
Background: We aimed to investigate whether there was a high incidence of young Japanese mothers being underweight (pregravid body mass index [BMI] < 18.5 kg/m2) and if they delivered infants who were small for gestational age (SGA).Materials and methods: Our study was carried out from 2013 to 2017 and included adolescent women (maternal age at delivery: <20 years old; n = 94), women in their early twenties (maternal age at delivery: 20-24 years; n = 479), and controls (maternal age at delivery: 25-34 years; n = 2061).Results: In both the adolescent and early twenties groups, the incidence of being underweight, based on prepregnancy BMI, was significantly higher than controls (p < .0001 and p < .05, respectively). In both groups, gestational weight gain (GWG) was significantly higher than controls (p < .0001). There were no notable group differences in the incidences of SGA.Conclusion: The incidence of being underweight was higher in younger mothers than in controls. However, the risk of SGA did not increase in younger mothers, possibly because their GWG overcame the influence of their pre-pregnancy body composition.


The Adaptation of the Substance Use Stigma Mechanism Scale (SU-SMS) Into Turkish: A Validity and Reliability Study.
Substance users are among the most highly stigmatized individuals by both the public and health care providers. However, no multidimensional scale for measuring substance use stigma for substance use disorders (SUDs) currently exists in Turkey. The aim of this study was to determine the validity and reliability of the Turkish version of the Substance Use Stigma Mechanism Scale (SU-SMS). The study was conducted at the AMATEM (Alcohol and Substance Addiction Treatment Center Clinic). The sample group of this methodological study consisted of 156 participants with SUDs who met the inclusion criteria. "Social-demographics Questionnaire," "The Substance Use Stigma Mechanism Scale," and "Internalized Stigma of Mental Illness Scale" were used for data collection. In the validity-reliability analysis of the scale, language and content validity, explanatory and confirmatory factor analysis, criterion-concurrent validity, Cronbach's alpha coefficient, item-total score correlation, split-half reliability analysis, and test-retest reliability methods were used. Using exploratory factor analysis, it was found that the SU-SMS has five factors. Its five-factor structure was confirmed using confirmatory factor analysis. Its Cronbach's alpha coefficient was .828, and factor loading was between .402 and .971. Analyses indicated that each of the factors of the Turkish version of the scale had high internal consistency. The test-retest correlation value was .752, p = .000. It was concluded that the Turkish version of the SU-SMS is a reliable and valid instrument for assessing substance use-related stigma in individuals with SUDs.


An Experimental and Numerical Investigation of Cardiac Tissue-Patch Interrelation.
Tissue engineered cardiac patches have great potential as a regenerative therapy for myocardial infarction. Yet, the mutual interaction of cardiac patches with healthy tissue has not been completely understood. Here, we investigated the impact of acellular and cellular patches on a beating two-dimensional (2D) cardiac cell layer, and the effect of the beating of this layer on the cells encapsulated in the patch. We cultured human-induced pluripotent stem cell-derived cardiomyocytes (iCMs) on a coverslip and placed gelatin methacryloyl hydrogel alone or with encapsulated iCMs to create acellular and cellular patches, respectively. When the acellular patch was placed on the cardiac cell layer, the beating characteristics and Ca+2 handling properties reduced, whereas placing the cellular patch restored these characteristics. To better understand the effects of the cyclic contraction and relaxation induced by the beating cardiac cell layer on the patch placed on top of it, a simulation model was developed, and the calculated strain values were in agreement with the values measured experimentally. Moreover, this dynamic culture induced by the beating 2D iCM layer on the iCMs encapsulated in the cellular patch improved their beating velocity and frequency. Additionally, the encapsulated iCMs were observed to be coupled with the underlying beating 2D iCM layer. Overall, this study provides a detailed investigation on the mutual relationship of acellular/cellular patches with the beating 2D iCM layer, understanding of which would be valuable for developing more advanced cardiac patches.


Transcription signals in a region essential for replication of plasmid R6K.
A DNA fragment encoding for the enzyme chloramphenicol acetyltransferase (CAT) but lacking the CAT promoter sequence was used to probe transcription signals in a DNA fragment (640 base pairs) from plasmid R6K that plays a central role in R6K DNA replication. The R6K DNA fragment analyzed contains the seven 22-bp direct repeats which express R6K incompatibility and are required in cis for activity of all three of the R6K origins of replication. In addition to the previously identified promoter sequences for the R6K initiation protein pi (P pi), a relatively weak transcriptional promoter upstream to P pi was detected. On the opposite strand an efficient (94%) transcriptional terminator was identified. This terminator is located upstream to nucleotide sequences active in the repression of R6K DNA replication.


Radiofrequency catheter ablation for intra-atrial reentrant tachycardia after surgery of atrial septal defect: use of isopotential mapping (QMS system) to demonstrate bidirectional complete block.
A 51 year-old Japanese man who had undergone surgical correction of an atrial septal defect at the age of 18 years old was referred to our institute for evaluation of his atrial arrhythmia. The conventional electrophysiological study was combined with a new technique utilizing an isopotential and isochronal mapping system (QMS) to visualize the electrical signals recorded with a 64-electrode basket catheter. Using this system, an intra-atrial reentrant tachycardia (IART) was demonstrated. The isopotential map recorded with the QMS (QMS-isoP) rapidly revealed a clockwise global reentrant circuit in the mid free wall of the right atrium and a narrowest activation isthmus between the lower end of the atriotomy scar and the inferior vena cava (IVC). After confirming entrainment with concealed fusion at the lower end of the atriotomy scar, radiofrequency energy was delivered linearly from this site to the IVC by slowly dragging the catheter. The elimination of the IART was defined by the QMS-isoP which demonstrated bidirectional block during pacing from both sides of the ablated linear lesion. The conventional technique of entrainment with concealed fusion combined with the QMS-isoP may result in a highly sophisticated method for identifying global reentrant circuits and for defining bidirectional block after eliminating the IART.


Malnutrition assessed by phase angle determines outcomes in low-risk cardiac surgery patients.
Phase angle (PA), which is obtained from bioelectrical impedance analysis (BIA), is a non-invasive method for measuring altered electrical properties of biological tissues. It has been recognised as an objective prognostic marker of disease severity and frailty. The aim of this study is to determine whether PA is a marker of malnutrition and postoperative morbidity in low operative risk patients undergoing cardiac surgery. A prospective study was conducted in a tertiary hospital. The nutritional state of the cardiac surgery patients was evaluated using BIA the day before the scheduled surgery. After applying selection criteria, 342 low operative risk patients were selected and classified into two groups in accordance with the PA value: a low PA group and a normal PA group. The correlation between low PA and low fat-free mass index (FFMI), a marker of malnutrition, was assessed. Associations between low PA and adverse postoperative outcomes, defined by the Society of Thoracic Surgeons postoperative risk evaluation model, were analysed. The impact of low PA on length of stay in an ICU and hospital was evaluated. Low PA was detected in 61 (17.8%) patients in the selected group, which consisted of low operative risk patients with a median Euroscore II value of 1.46 (IQR: 0.97-2.03) and was associated with FFMI with Pearson's R of 0.515 (p < 0.001). Low PA was associated with higher rates (13 [21.3%] vs. 30 [10.7%] p = 0.023) and risk of postoperative morbidity in univariate regression analysis (OR = 2.27, Cl 95% = 1.10-4.66, p = 0.026). Furthermore, low PA persisted as an independent factor in multivariate regression analysis (OR = 2.50, CI 95% 1.18-5.29, p = 0.016) adjusted for preoperative risk factors of postoperative morbidity. Evaluation of hospitalisation length revealed a tendency of a prolonged hospitalisation (>14 days) rate (31 [50.8%] vs. 105 [37.8%], p = 0.063) in the group with low PA. A low preoperative PA is an indicator of malnutrition and determines adverse outcomes after cardiac surgery. Further research is needed to evaluate clinical applications of the PA, such as a more accurate identification of malnourished cardiac surgery patients.


Scholastic psychological well-being and irrational thoughts in students of primary and secondary school: An Italian study.
The period of pre-adolescence is a period of age transition during which undesirable feelings such as anxiety, shyness, guilt, depression and anger are experienced accompanied by physical and hormonal changes experienced during puberty. Therefore, during early adolescence the psychological well-being is a critical issue. This period of transition coincides to the passage from the primary to the secondary school in Italy. This transition could have some effects on the psychological well-being on children, in particular on their scholastic well-being. In addition, during early adolescence children develop irrational thoughts. We tested, therefore, the variation of scholastic well-being and irrational thoughts in children of the primary (n = 50; mean age 10.5; 56 % females) and secondary school (n = 61; mean age 11.5; 49 % females). Results showed that children of the secondary school have lower scholastic well-being and higher level of irrational thoughts than children of primary school. In particular, during the transition from the primary to the secondary school, children showed a lower level of satisfaction with academic results and the perception of a low support from their teachers. In addition, there was also a stronger reduction of self-esteem and an increment of distrust in achieving scholastic success. A scholastic psychological support, with particular attention to the emotional development of early-adolescents, is suggested.


Molecular dynamics simulation of dipalmitoylphosphatidylcholine modified with a MTSL nitroxide spin label in a lipid membrane.
We investigate the interaction between dipalmitoylphosphatidylcholine (DPPC) and a nitroxide spin label in order to understand its influences on lipid structure and dynamics using molecular dynamics simulations. The system was modified by covalently attaching nitroxide spin labels to the headgroups of two DPPC molecules. (S-(2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl methanesulfonothioate) (MTSL) was used as the spin label. The label position and dynamics were analyzed as was the impact of the modified DPPC on the structure of the surrounding lipids. The modified DPPC molecules locate closer to the center of the membrane than unmodified DPPC molecules. The rotation of the spin label is unrestricted, but there are favored orientations. MTSL depresses the deuterium order parameters of the carbon atoms close to the headgroup in surrounding DPPC molecules. The spin label has no impact on order parameters of carbon atoms at the end of the lipid tails. The lateral diffusion constant of the modified DPPC is indistinguishable from unmodified DPPC molecules. These novel computational results suggest an experimental validation.


The reduction of methemerythrin by e-aq and CO2- from pulse radiolysis studies.
The rate constants for reduction of methemerythrin from Phascolopsis gouldii and Themiste pyroides by hydrated electrons are 2.0 and 3.9 x 10(9) M(-1)s(-1), respectively, at pH 8.2, I = 0.03 M, and 25 degrees C. There is only a small increase in rate when the pH is lowered to 6.3 and a very small decrease when the ionic strength is raised to 0.1 M. Adding azide ion (to form the met-azide adduct) has little effect on the reactivity towards e-aq. For the monomer form, metmyohemerythrin from T. pyroides, the reaction rate constant is 4.5 x 10(9) M(-1)s(-1). Methemerythrin from T. pyroides reacts with CO2- with a rate constant 6.8 x 10(7) M(-1)s(-1). The reactivity sequence e-aq greater than CO2- greater than SO2- (from dithionite reduction) towards methemerythrin is the same as that observed with reduction of heme proteins but the rate constants are some 10 to 100 times smaller for the former. Only 10 to 20% of the e-aq or CO2- radicals generated effect reduction of the iron centers in methemerythrin.


Development of synaptic ultrastructure at neuromuscular contacts in an amphibian cell culture system.
Cultures of dissociated myotomal muscle and spinal cord derived from embryos of Xenopus laevis were grown in the presence of curare in order to abolish neuromuscular activity and were examined by electron microscopy. In one-day-old cultures a few of the neuromuscular contacts already displayed several synaptic specializations including 500 A vesicles clustered against the axolemma, increased axolemmal densities, basal lamina in the cleft, an increased sarcolemmal density and subsarcolemmal filamentous material. Contacts with these specializations were observed more frequently in two and three-day-old cultures. Throughout the three-day culture period nerve fibres and neuromuscular contacts were devoid of Schwann cells. Isolated patches of basal lamina were relatively scarce and were usually accompanied by an increase in sarcolemmal density and subsarcolemmal filamentous material even in cultures in which spinal cord cells were not included. These observations indicate that the myotomal neuromuscular synapse differentiates in culture in much the same way as it does in vivo, that muscle contractions are not required for its differentiation, and that apparent postsynaptic specializations can develop in the absence of innervation.


Psychometric validation and clinical validity of the Minor Melancholia Mood Checklist (MMCL-32).
The Minor Melancholia Mood Checklist (MMCL-32) was developed to identify sub-threshold states of major depression. The MMCL-32 can be considered as the counterpole to the Hypomanic Check List (HCL-32). Principal component analysis (PCA) without rotation was used to identify a bidirectorial principal component. To evaluate the clinical validity of the bidirectorial factors, with reference to brief recurrent depression, the Bech-Rafaelsen Melancholia Scale was used. We included 59 patients with bipolar I disorder (SCID criteria) and 57 patients with unipolar depression (more than one major depressive episode without hypomanic or manic episodes). They were all outpatients, but had recently been discharged from inpatient treatment. The PCA identified two contrasting factors: 17 items with negative loadings (psychasthenic depression factor) and 15 items with positive loadings (cognitive depression factor). When PCA was applied exclusively to the bipolar patients, 5 items within the cognitive factor were identified. When applied exclusively to the unipolar patients, 5 items within the psychasthenic factor were identified. The non-remitted bipolar patients scored higher on the cognitive factor (P=0.01) than the remitted. On the psychasthenic factor (P=0.06), the non-remitted unipolar patients scored higher than the remitted patients. The MMCL-32 was found psychometrically valid in measuring sub-threshold states of major depression with rather specific factors for bipolar and unipolar depression. Focusing on these factors could be a clinical aid to distinguish patients at risk of developing a bipolar course.


Determination of aflatoxins with state-of-the-art chromatographic methods: Problems to overcome.
Methods for wide acceptance should be environmental friendly, robust and rapid, and based on regulatory and guidline limits, recommendations of standardization organisations, economical and ecological aspects and accuracy. Methods following such proposals are described for determination of aflatoxins in peanut butter, pistachio paste, figs, paprika powder and baby food.


Verbal associative memory outcomes in pediatric surgical temporal lobe epilepsy: Exploring the impact of mesial structures.
We examined verbal associative memory outcomes in children with left- or right-sided temporal lobe epilepsy (TLE) who received combined lateral and mesial resections versus lateral resections sparing mesial structures. We hypothesized that children who underwent left-sided resections including mesial structures would show the greatest verbal associative memory declines following surgery. We retrospectively analyzed neuropsychology assessment results from a sample of 65 children with TLE who completed pre- and postoperative evaluation at the Hospital for Sick Children in Toronto, Canada. We examined verbal associative memory score changes between groups by laterality (left versus right) and resection type (lateral only versus lateral and mesial resection). We also explored potential associations between certain epilepsy-related characteristics and verbal associative memory changes. Postoperative decline was found in children with left-sided resections, but not those with right-sided resections. In children who received left-sided resections, there was some suggestion of verbal associative memory decline in those who had both lateral and mesial tissues excised, but not in those with lateral resections only. Notably, there was also a language dominance (typical versus atypical) by resection type interaction. Specifically, for the typical language group, children with left lateral plus mesial resections (but not mesial sparing resections) showed postoperative verbal associative memory declines, whereas the opposite was true for the atypical language group. These data contribute to our growing understanding of verbal memory outcomes following TLE in childhood, with consideration of the extent of resection to mesial structures. Our findings also highlight the importance of language laterality when interpreting neuropsychological assessment findings and making predictions regarding risk of functional loss following surgery.


Colonoscopy using a small-caliber colonoscope with passive-bending after incomplete colonoscopy due to sharp angulation or pain.
We evaluated the performance of a newly developed small-caliber (SC) colonoscope (PCF-PQ260L). This colonoscope (diameter 9.2 mm) is designed with passive-bending and high-force transmission. The SC colonoscope was used for rescue colonoscopy following incomplete colonoscopy with a standard (SD) colonoscope caused by sharp angulation, loop formation, or pain. Records of SC colonoscopy given to patients following an incomplete colonoscopy with the SD colonoscope and in the same session were analyzed. Cecal intubation rate, pain using a visual analog scale (0 = none, 100 = extremely painful) in the first and second colonoscopy, total time, new lesions detected with the SC colonoscopy, dosage of sedation used, and any complications were assessed. Examinations that could not be completed, because the colonoscope was not long enough to reach the cecum due to a redundant colon were excluded. The records of 43 patients who were given SC colonoscopy following incomplete examinations using the SD colonoscope were reviewed. In 97.7 % of cases (42/43), cecal intubation was achieved with the SC colonoscope in the same session. The mean pain score during colonoscopy was significantly lower for the second SC colonoscopy than for the first SD colonoscopy (40.6 ± 14.1 vs. 74.5 ± 10.8, P < 0.001). Lesions were detected with the SC colonoscope in 41.8 % of cases (18/43). When a colonoscopy with SD colonoscope failed due to sharp angulations, loop formation, or pain, subsequent colonoscopy with a SC colonoscope increased cecal intubation and lesion detection rates and decreased severity of reported pain.


Complete kinetic mechanism of elongation factor Tu-dependent binding of aminoacyl-tRNA to the A site of the E. coli ribosome.
The kinetic mechanism of elongation factor Tu (EF-Tu)-dependent binding of Phe-tRNAPhe to the A site of poly(U)-programmed Escherichia coli ribosomes has been established by pre-steady-state kinetic experiments. Six steps were distinguished kinetically, and their elemental rate constants were determined either by global fitting, or directly by dissociation experiments. Initial binding to the ribosome of the ternary complex EF-Tu.GTP.Phe-tRNAPhe is rapid (k1 = 110 and 60/micromM/s at 10 and 5 mM Mg2+, 20 degreesC) and readily reversible (k-1 = 25 and 30/s). Subsequent codon recognition (k2 = 100 and 80/s) stabilizes the complex in an Mg2+-dependent manner (k-2 = 0.2 and 2/s). It induces the GTPase conformation of EF-Tu (k3 = 500 and 55/s), instantaneously followed by GTP hydrolysis. Subsequent steps are independent of Mg2+. The EF-Tu conformation switches from the GTP- to the GDP-bound form (k4 = 60/s), and Phe-tRNAPhe is released from EF-Tu.GDP. The accommodation of Phe-tRNAPhe in the A site (k5 = 8/s) takes place independently of EF-Tu and is followed instantaneously by peptide bond formation. The slowest step is dissociation of EF-Tu.GDP from the ribosome (k6 = 4/s). A characteristic feature of the mechanism is the existence of two conformational rearrangements which limit the rates of the subsequent chemical steps of A-site binding.


Effect of graded mechanical ischemia on oxygen tension and electrical potential in the canine gastric mucosa. A new experimental model.
Oxygen tension and potential difference were measured in the gastric mucosa of anesthetized dogs with an ultramicroelectrode technqiue while total blood flow and arteriovenous oxygen content difference were measured. In the control period, measurements were: gastric blood flow, 102.4 +/- 3.0 ml per min per 100 g of tissue; calculated oxygen consumption, 2.4 +/- 0.1 ml per min per 100 g of tissue; intracellular oxygen tension, 15.0 +/- 0.6 mm Hg; and intracellular potential difference, -50.8 +/- 1.5 mv. When gastric blood flow was reduced 50% by tourniquet ischemia, oxygen tension decreased 20% (P less than 0.05) but electrical potential and oxygen consumption did not change. When blood flow was reduced 75%, oxygen tension and potential difference decreased significantly, 60% and 35%, respectively, but oxygen consumption was unchanged. Zero blood flow reduced oxygen tension, electrical potential, and total oxygen consumption to zero; release of the arterial tourniquet allowed them to return to control levels. The critical oxygen tension at which the electromotive force generated by the gastric mucosal cells was reduced averaged 9 mm Hg. This suggests that safety factors exist in the gastric circulation which permit a 60% reduction in total gastric blood flow to occur before an insufficiency of intracellular oxygen begins to limit cellular metabolism within the mucosa.


Increased resolution of lipopolysaccharides and lipooligosaccharides utilizing tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
We utilized the recently described tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (TSDS-PAGE) system to study the lipooligosaccharides (LOS) and lipopolysaccharides (LPS) of gram negative bacteria. TSDS-PAGE resulted in a high degree of resolution of LOS and LPS in the 'mini-gel' format. TSDS-PAGE resulted in the LOS and LPS migrating as a function of their Mr during electrophoresis and allowed estimation of Mr from a protein standard. Several species of LOS were analyzed. The newly described procedure allowed a more rapid and accurate analysis of LOS and the core region of LPS.


A Call for Eminence Obstetrics Care by Way of "Neonatal Near Miss" Events (NNM): A Hospital-Based Case-Control Study.
A neonatal near miss (NNM) case would refer to an infant who nearly died but survived during birth or within 28 days of extra-uterine life. The near miss concept is being increasingly used as a tool to evaluate and improve the quality of care, especially obstetric care. All "near miss" should be inferred as free lesson and opportunities to improve the quality of service endowment. A hospital based case control study was conducted in a tertiary care hospital of central Gujarat to measure factors associated with NNM events. Mothers of those newborns, who had been admitted for critical care, and survived, were included as cases, after their discharge. Controls were selected from same settings who were not falling into defined criteria of NNM. Various antenatal factors were compared among the two groups. The number of neonatal near miss events were 291 (109 newborns with birth weight less than 1500 g, 169 APGAR score <7 and 13 with gestational age <30 weeks). The neonatal near miss rate was 86.7 per 1000 live births. Less number of antenatal visits, history of referral and hospitalisation during ante natal period were adversely associated with near miss events. Incorporation of near miss events into the confidential enquiry system is worthwhile for corrective interventions like quality antenatal care, timely screening and referral of pregnant women into the primary health care system.


Sexual function with localized prostate cancer: active surveillance vs radical therapy.
Study Type - Outcomes (cohort sample) Level of Evidence 2b. What's known on the subject? and What does the study add? The study compares the sexual function of men with low-risk prostate cancer who chose active surveillance (expectant management) with similar men who received radiation therapy or radical prostatectomy. The first group appeared to be sexually active more frequently and had less erectile dysfunction. The study was non-randomized. No other studies exist on the effect of active surveillance on sexual function vs other treatment methods. To compare sexual function of men with localized prostate cancer (PCa) on active surveillance (AS) with similar patients who received radical therapy. Two groups of men with screening-detected localized PCa were compared. The first were men on AS within the prospective protocol-based Prostate Cancer Research International: Active Surveillance study. The second were men participating in the European Randomized Study of Screening for Prostate Cancer study who had received radical prostatectomy (RP) or radiation therapy (RT). • Questionnaires were completed at two different timepoints after diagnosis or treatment (6 and 12-18 months). These contained 10 items on sexual function, the mental and physical component summary from the Short-Form 12-item health survey, the Center for Epidemiologic Studies Depression scale depression measure and the State Trait Anxiety Inventory general anxiety measure. • Sexual function was compared between groups, and determinants were analysed in multivariable analysis, adjusting for baseline differences. A total of 65-68% of men on AS, 35-36% of those who underwent RP, 36-37% of those who underwent RT and 36% of men in the RP and RT groups combined (combined Tx) were sexually active. • A total of 20-30% of men in the AS group, 86-91% of men in the RP group, 56-60% of men in the RT group and 71-76% of men in the combined Tx group were sexually inactive as a result of erectile dysfunction. • A total of 44-51% of men in the AS group, 96% of men in the RP group, 73-76% of men in the RT group and 84-85% of men in the combined Tx group who were sexually active had problems getting or keeping an erection. • In multivariable analysis these differences were significant, except for AS vs RT. Men with localized PCa on AS were more often sexually active than similar men who received radical therapy, especially RP. If not sexually active, this was less often attributable to erectile dysfunction for those on AS. If sexually active, this was less often associated with problems getting or keeping an erection for those on AS. • The study was non-randomized; the latest advances in RP and RT might impact results.


Sero-survey for Legionella pneumophila antibodies--Singapore experience.
One hundred and fifty blood bank donors were sero-surveyed for legionella antibodies by indirect immunofluorescence test using a polyvalent antigen group (1 to 4). 20% of the group surveyed had an antibody titre greater than or equal to 16 to the organism. This paper also reports a study on 166 hospitalised acute pneumonia patients. The sera from these patients were screened for L. pneumophila antibodies; 5 of the patients had significant antibody titre greater than or equal to 256 which is diagnostic of legionellosis.


Prevalence of silent myocardial ischaemia in new-onset middle-aged Type 2 diabetic patients without other cardiovascular risk factors.
Coronary artery disease (CAD) is the leading cause of death in patients with Type 2 diabetes and is often asymptomatic. Silent myocardial ischaemia (SMI) is frequent in diabetic subjects and is responsible for a late diagnosis of CAD; its early detection is important. There are some data about the prevalence of SMI in Type 2 diabetic patients at high risk for cardiovascular disease, while no data are available in subjects at the onset of diabetes without other cardiovascular risk factors. We screened 274 consecutive patients (mean age 64.3 +/- 8.4 years, 66% male) at the time of diagnosis of Type 2 diabetes; we enrolled 111 subjects without other cardiovascular disease risk factors (dyslipidaemia, hypertension, peripheral vascular disease, retinopathy, microalbuminuria, history of heart disease) and with normal resting electrocardiogram (ECG). Participants performed a maximal ECG exercise protocol and, if positive, underwent coronary angiography. The ECG exercise test was positive in 19 patients (17.1%); of those 14 (13%) had angiographic coronary disease (one with three-vessel disease, three with two vessels and 10 with one vessel involved). The positive predictive value of the exercise ECG for predicting angiographic coronary disease was 73%. The prevalence of SMI was 17% and angiographic coronary disease was found in 13% of middle-aged subjects with new-onset Type 2 diabetes without other cardiovascular risk factors. This prevalence is similar to that observed in studies of subjects with long duration diabetes who have additional cardiovascular risk factors.


QUARTIC: QUick pArallel algoRithms for high-Throughput sequencIng data proCessing.
Life science has entered the so-called 'big data era' where biologists, clinicians and bioinformaticians are overwhelmed with unprecedented amount of data. High-throughput sequencing has revolutionized genomics and offers new insights to decipher the genome structure. However, using these data for daily clinical practice care and diagnosis purposes is challenging as the data are bigger and bigger. Therefore, we implemented software using Message Passing Interface such that the alignment and sorting of sequencing reads can easily scale on high-performance computing architecture. Our implementation makes it possible to reduce the time to delivery to few minutes, even on large whole-genome data using several hundreds of cores.


Ultrasound detection of unusual spontaneous portosystemic shunts associated with uncomplicated portal hypertension.
Seven cases of unusual spontaneous portosystemic shunts observed by ultrasonography in the last 8 months are reported, including cases of coronary vein varicocele and patent umbilical vein; two cases of spleno-retroperitoneal anastomosis; omphalo-ilio-caval anastomosis; superior mesenteric vein-inferior vena cava anastomosis; spleno-renal anastomosis; and spleno-portal anastomosis and anastomosis from the splenic vein to the abdominal wall. One of these collateral vessels was also analyzed by pulsed Doppler flowmetry. The patients were either cirrhotic or had pre-hepatic portal hypertension (resulting from chronic pancreatitis) and gave no history of gastrointestinal bleeding or ascites. Two of these patients had previously undergone surgery for problems associated with cholestasis. In both cases, presurgical sonographic studies were used to guide the surgical procedures in the hope of preserving the anomalous connections. Furthermore, ultrasound detection of spontaneous portosystemic shunts was an important factor in interpreting the clinical symptoms of these patients.


Prototypic Lightweight Alloy Design for Stellar-Radiation Environments.
The existing literature data shows that conventional aluminium alloys may not be suitable for use in stellar-radiation environments as their hardening phases are prone to dissolve upon exposure to energetic irradiation, resulting in alloy softening which may reduce the lifetime of such materials impairing future human-based space missions. The innovative methodology of crossover alloying is herein used to synthesize an aluminium alloy with a radiation resistant hardening phase. This alloy-a crossover of 5xxx and 7xxx series Al-alloys-is subjected to extreme heavy ion irradiations in situ within a TEM up to a dose of 1 dpa and major experimental observations are made: the Mg32(Zn,Al)49 hardening precipitates (denoted as T-phase) for this alloy system surprisingly survive the extreme irradiation conditions, no cavities are found to nucleate and displacement damage is observed to develop in the form of black-spots. This discovery indicates that a high phase fraction of hardening precipitates is a crucial parameter for achieving superior radiation tolerance. Based on such observations, this current work sets new guidelines for the design of metallic alloys for space exploration.


Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration.
The pharmacokinetics of orphenadrine (ORPH) following a single intravenous (i.v.) dose was investigated in six camels (Camelus dormedarius). Orphenadrine was extracted from the plasma using a simple sensitive liquid-liquid extraction method and determined by gas chromatography/mass spectrometry (GC/MS). Following i.v. administration plasma concentrations of ORPH decline bi-exponentially with distribution half-life (t(1/2)(alpha)) of 0.50+/-0.07h, elimination half-life (t(1/2)(beta)) of 3.57+/-0.55h, area under the time concentration curve (AUC) of 1.03+/-0.10g/hl(-1). The volume of distribution at steady state (Vd(ss)) 1.92+/-0.22lkg(-1), volume of the central compartment of the two compartment pharmacokinetic model (V(c)) 0.87+/-0.09lkg(-1), and total body clearance (Cl(T)) of 0.60+/-0.09l/hkg(-1). Three orphenadrine metabolites were identified in urine samples of camels. The first metabolite N-desmethyl-orphenadrine resulted from N-dealkylation of ORPH with molecular ion m/z 255. The second N,N-didesmethyl-orphenadrine, resulted from N-didesmethylation with molecular ion m/z 241. The third metabolite, hydroxyl-orphenadrine, resulted from the hydroxylation of ORPH with molecular ion m/z 285. ORPH and its metabolites in camel were extensively eliminated in conjugated form. ORPH remains detectable in camel urine for three days after i.v. administration of a single dose of 350mg orphenadrine aspartate.


Recent developments, challenges, and prospects of ultrasound-assisted oil technologies.
There has been consistent drive towards research and innovation in oil production technologies in order to achieve improved effectiveness and efficiency in their operation. This drive has resulted in breakthrough in technologies such as the application of ultrasound (US) in demulsification and enhanced oil recovery (EOR), and usage of high-volume hydraulic fracturing and special horizontal well for shale oil and gas extraction. These can be observed in the increment in the number of commercial oil technologies such as EOR projects that rose from 237 in 1996 to 375 in 2017. This sustained expansion in EOR resulted in their total oil production rising from 1.5 million barrels per day in 2005 to 2.3 million barrels per day in 2020. And this is predicted to increase to about 4.7 million barrels per day in 2040, which represent about 4% of total production. Consequently, in this review, the developments in the utilization of US either as standalone or integrated with other technologies in EOR and dehydration of water in oil emulsions were analyzed. The studies include the optimization of fluid and US properties in EOR and demulsification. Reports on the treatment of formation damage resulting from inorganic salts, organic scales, drilling fluid plugs, condensate, paraffin wax and colloidal particle with US-assisted EOR were also highlighted. Moreover, the mechanisms were examined in order to gain insightful understanding and to aid research investigations in these areas. Technologies such as US assisted green demulsification, high intensity focused ultrasound, and potential pathways in field studies were assessed for their feasibilities. It is essential to evaluate these technologies due to the significant accrued benefits in them. The usage of green demulsifiers such as deep eutectic solvents, ionic liquids and bio-demulsifiers has promising future outlook and US could enhance their technical advancement. HiFU has been applied successfully in clinical research and developments in this area can potentiality improve demulsification and interfacial studies (fluid-fluid and solid-fluid interactions). As regards field studies, there is need to increase actual well investigations because present reports have few on-site measurements with most studies being in laboratory scale. Furthermore, there is need for more detailed modeling of these technologies as it would assist in conserving resources, saving research time and fast-tracking oil production. Additional evaluative studies of conditions such as the usage of Raschig rings, crude oil salinity and high temperature which have improved demulsification of crude oil emulsions should be pursued.


Acute and late disease induced by murine coronavirus, strain JHM, in a series of recombinant inbred strains between BALB/cHeA and STS/A mice.
To examine the genetic control of acute and late disease induced by a murine coronavirus, strain JHM (JHMV), BALB/cHeA, STS/A, F1 hybrids and 13 recombinant inbred (RI) strains between BALB/cHeA and STS/A mouse strains were inoculated intracerebrally with 100 pfu of JHMV. All the BALB/cHeA mice died within 2 weeks from acute encephalitis. In contrast, STS/A mice were shown to be partially resistant, with a mortality rate of 30%, longer survival times and lower rates of viral production. The mortality rates, survival times and viral titers of F1 hybrids and the RI strains varied, suggesting involvement of multiple genes. STS/A, F1 hybrid and RI mice surviving the acute infection occasionally developed severe paraparesis about 1 month post-infection. In these mice, vacuolar degeneration, astrocytosis, the absence of perivascular cuffing and minimal demyelination were found in the central nervous system. No infectious virus could be recovered from these mice. Although the paralysis of delayed onset was limited to STS/A, F1 hybrid and eight of the 13 RI strains, the incidence varied significantly among the RI strains. These results may suggest that JHMV-induced late disease is also under multifactorial control. The pathogenesis of JHMV infection is discussed.


Pathogenesis of persistent truncus arteriosus in light of observations made in a dog embryo with the anomaly.
Among 36 embryos obtained from a strain of Keeshond dogs in which there is a large incidence of spontaneously occurring conotruncal anomalies, a specimen with persistent truncus arteriosus, type 1 was found. The embryo had a crown-rump length of 20 mm. The specimen was serially sectioned and a wax plate reconstruction was made of the heart and proximal great vessels at a magnification of X100. The truncal valve was quadricuspid and dysplastic; associated anomalies were a right subclavian artery arising anomalously from the descending aorta, a single coronary artery, an absent ductus arteriosus and a small persistent left cranial (superior) vena cava. The truncus cushions were hypoplastic, had failed to fuse and each had simply produced an arterial cusp. The observations made on this embryo support the view that in persistent truncus arteriosus there is failure of septation of the truncus arteriosus. No evidence was found in favor of the concept that persistent truncus arteriosus represents a form of tetralogy of Fallot with atresia of the subpulmonary infundibulum and partial or complete absence of the aorticopulmonary septum.


DNA gyrase activities from Rhodobacter capsulatus: analysis of target(s) of coumarins and cloning of the gyrB locus.
Bacterial DNA gyrase is composed of two subunits, gyrase A and B, and is responsible for negatively supercoiling DNA in an ATP-dependent manner. The coumarin antibiotics novobiocin and coumermycin are known inhibitors of bacterial DNA gyrase in vivo and in vitro. We have cloned, mapped, and partially sequenced Rhodobacter capsulatus gyrB which encodes the gyrase B subunit that is presumably involved in binding to coumarins. DNA gyrase activities from crude extracts of R. capsulatus were detected and it was shown that the R. capsulatus activity is (1) inhibited by novobiocin and coumermycin, (2) ATP-dependent and, (3) present in highly aerated and anaerobically grown cells. We previously observed that when R. capsulatus coumermycin-resistant strains are continuously recultured on media containing coumermycin they sometimes acquired mutations in hel genes (i.e., cytochromes c biogenesis mutations). We discuss the possibility that coumarins may inhibit cytochromes c biogenesis as a second target in R. capsulatus via hel (i.e., a putative ATP-dependent heme exporter).


Generalized blind delayed source separation model for online non-invasive twin-fetal sound separation: a phantom study.
The fetal phonocardiogram, which is the acoustic recording of mechanical activity of the fetal heart, facilitates the measurement of the instantaneous fetal heart rate, beat-to-beat differences and duration of systolic and diastolic phases. These measures are sensitive indicators of cardiac function, reflecting fetal well-being. This paper provides an algorithm to non-invasively estimate the phonocardiogram of an individual fetus in a multiple fetus pregnancy. A mixture of fetal phonocardiograms is modeled by a generalized pure delayed mixing model. Mutual independence of fetal phonocardiograms is assumed to apply blind source separation based techniques to extract the fetal phonocardiograms from their mixtures. The performance of the algorithm is verified through simulation results and on experimental data obtained from a phantom that is used to simulate a twin pregnancy.


Interplay between persistent activity and activity-silent dynamics in the prefrontal cortex underlies serial biases in working memory.
Persistent neuronal spiking has long been considered the mechanism underlying working memory, but recent proposals argue for alternative 'activity-silent' substrates. Using monkey and human electrophysiology data, we show here that attractor dynamics that control neural spiking during mnemonic periods interact with activity-silent mechanisms in the prefrontal cortex (PFC). This interaction allows memory reactivations, which enhance serial biases in spatial working memory. Stimulus information was not decodable between trials, but remained present in activity-silent traces inferred from spiking synchrony in the PFC. Just before the new stimulus, this latent trace was reignited into activity that recapitulated the previous stimulus representation. Importantly, the reactivation strength correlated with the strength of serial biases in both monkeys and humans, as predicted by a computational model that integrates activity-based and activity-silent mechanisms. Finally, single-pulse transcranial magnetic stimulation applied to the human PFC between successive trials enhanced serial biases, thus demonstrating the causal role of prefrontal reactivations in determining working-memory behavior.


Risk predictors for adverse outcomes after percutaneous coronary interventions and their related costs.
During recent years, numerous clinical and procedural risk factors for adverse outcomes after percutaneous coronary interventions (PCI) have been identified. Due to the high economic pressure in many national health care systems, it is of some interest whether these predictors of clinical risks represent also the main cost drivers. Data of 770 patients undergoing PCI were retrospectively analyzed. Risk factors for PCI as well as angiographic classifications were adopted from the ACC/AHA Guidelines. In-hospital costs for each patient were obtained from thoroughly performed calculations for the national Diagnosis Related Groups database in Germany. Creatinine >2 mg/dl (192% of average costs, P < 0.0001), EF <or= 35% (146%, P < 0.0001), presence of a thrombus (146%, P < 0.0001), PCI of a venous bypass (143%, P < 0.0001), CCS class IV (123%, P < 0.0001), coronary three-vessel disease (119%, P < 0.0001) and age (112%, P = 0.014) were associated with both higher in-hospital mortality and costs. Furthermore, in patients with acute coronary syndromes the time delay from onset of symptoms until PCI had marked impact on costs. Most predictors for adverse outcome after PCI were also found to be major cost drivers. Moreover, time delay from onset of ACS to PCI had marked impact on costs and should be implemented in the reimbursement systems.


Ionic channels of nerve: questions for theoretical chemists.
Ionic channels are the voltage-dependent, ion-selective pores of nerve membranes. They are probably macromolecules which change their conformation as the electric field is changed. One conformation makes the membrane permeable to ions. Physiologists need the help of physical chemists and theoretical chemists to understand channels better.


Trichodysplasia spinulosa: a benign adnexal proliferation with follicular differentiation associated with polyomavirus.
Trichodysplasia spinulosa is a rare polyomavirus-associated cutaneous eruption occurring in the setting of immunosuppression. Clinically it is characterised by multiple centrofacial folliculocentric papules with spinous protuberances. The histopathology is distinct and treatment with antiviral agents appears to be the most effective.


Multicenter comparison of the nifedipine gastrointestinal therapeutic system and long-acting propranolol in patients with mild to moderate systemic hypertension receiving diuretics. A preliminary experience.
The efficacy and safety of nifedipine in a gastrointestinal therapeutic system (GITS) push-pull osmotic pump formulation was compared with long-acting propranolol in 49 patients with mild to moderate hypertension already receiving diuretics. Using a two-week placebo run-in, double-blind study design, patients were randomly assigned to receive nifedipine GITS (n = 24) in doses of 30 mg, 60 mg, or 90 mg once daily; or long-acting propranolol (n = 25) in doses of 80, 160, or 240 mg once daily. Previous diuretic therapy was continued. Sitting and five-minute standing blood pressure and heart rate measurements were made 24 hours after dosing. At the endpoint of treatment, both nifedipine GITS and sustained-release propranolol reduced blood pressure compared with placebo (p less than 0.001) in the sitting and standing positions. Nifedipine GITS was more effective in lowering standing systolic blood pressure than was propranolol (p less than 0.02). Propranolol caused a greater reduction in resting heart rate than did nifedipine GITS (p less than 0.003). Both drugs were well tolerated. Nifedipine GITS is an effective and safe once-daily drug for use in patients with hypertension who are already receiving diuretics, may be more effective than sustained-release propranolol, and may be better tolerated than conventional nifedipine capsules.


Paternal factors contributing to embryo quality.
Advancing maternal and paternal age leads to a decrease in fertility, and hence, many infertile couples opt for assisted reproductive technologies [ART] to achieve biological parenthood. One of the key determinants of achieving a live outcome of ART, embryo quality, depends on both the quality of the oocyte and sperm that have created the embryo. Several studies have explored the effect of oocyte parameters on embryo quality, but the effects of sperm quality on the embryo have not been comprehensively evaluated. In this review, we assess the effect of various genetic factors of paternal origin on the quality and development of the embryo. The effects of sperm aneuploidy, sperm chromatin structure, deoxyribonucleic acid [DNA] fragmentation, role of protamines and histones, sperm epigenetic profile, and Y chromosome microdeletions were explored and found to negatively affect embryo quality. We propose that careful assessment of spermatozoal parameters is essential to achieve embryo development and a healthy live birth. However, the heterogeneity in test results and the different approaches of assessing a single sperm parameter highlight the need for more research and the development of standardized protocols to assess the role of sperm factors affecting embryo quality.


On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat.
1. The mechanism of action of picrotoxin on GABA receptor channels in rat sympathetic neurones has been investigated with whole-cell clamp. In addition, the action of picrotoxin on single GABA channels has been examined in outside-out membrane patches from these cells. 2. Picrotoxin, at concentrations which dramatically reduced the amplitude of whole-cell GABA currents, did not alter the spectral time constants or single-channel conductance estimated by analysis of GABA-activated current noise. This was observed at potentials both negative and positive to the GABA reversal potential (i.e. for both inward and outward GABA currents). In control conditions, the slow and fast time constants from GABA noise were 40 +/- 14 ms and 2 +/- 0.4 ms, while the estimated single-channel conductance was 14 +/- 2 pS. In the presence of picrotoxin, the time constants and estimated single-channel conductance were 41 +/- 5 ms, 2.7 +/- 0.6 ms and 15 +/- 2.3 pS. 3. Picrotoxin did not alter the shape of the whole-cell GABA current-voltage relationship, indicating that the steady-state block was not voltage dependent. The lack of effect of picrotoxin on the GABA noise spectra and the lack of outward rectification makes it unlikely that picrotoxin acts by a simple voltage-dependent (or voltage-independent) channel blocking mechanism. In the presence of picrotoxin the reversal potential for GABA remained at approximately 0 mV in symmetrical chloride. 4. Distributions of total burst durations, obtained from single-channel records with low concentrations of GABA, were fitted with three or four exponential components. Picrotoxin had no consistent effect on the time constants of the total burst length distributions. It also did not alter the amplitude of the main conductance state. However, picrotoxin did reduce the frequency of channel openings. 5. The application of brief ionophoretic pulses of GABA, to cells under whole-cell voltage clamp, revealed that the rate of onset of block by picrotoxin was accelerated in the presence of GABA. In the absence of agonist, picrotoxin produced a more slowly equilibrating block. 6. Our data are consistent with a mechanism whereby picrotoxin binds preferentially to an agonist bound form of the receptor and stabilizes an agonist-bound shut state. This could, for example, mean that picrotoxin enhances the occurrence of a desensitized state or an allosterically blocked state.


Increased expression of high mobility group box 1 (HMGB1) in the cytoplasm of placental syncytiotrophoblast from preeclamptic placentae.
Preeclampsia is a pregnancy-specific disorder characterised by an inappropriate maternal inflammatory response during pregnancy. High mobility group box 1 (HMGB1) was originally characterised as a nuclear protein but when released into the extracellular environment following necrotic cell death, it is proinflammatory. HMGB1 is expressed in the syncytiotrophoblast of human placenta. Higher levels of uric acid are reported in preeclampsia. The aim of this study was to investigate whether the expression of HMGB1differed between early onset and late onset preeclampsia or severe and mild preeclampsia and whether its expression correlated with the levels of uric acid. 74 preeclamptic placentae and 110 normotensive placentae were included in this study. The levels of uric acid in women with preeclampsia were measured. The expression of HMGB1 in preeclamptic placentae or in first trimester and term placentae that had been treated with uric acid was measured. HMGB1 was expressed predominantly in the syncytiotrophoblast of the placenta and the expression of HMGB1 in the cytoplasm of the syncytiotrophoblast was significantly increased in both severe preeclampsia and early onset preeclampsia compared to normotensive pregnancies. The circulating levels of uric acid were significantly increased in preeclampsia and correlated with the expression of HMGB1. Increased levels of HMGB1 were significantly correlated with the severity and the time of onset of preeclampsia, but pathologic levels of uric acid did not increase the expression of HMGB1. Our data provides a better understanding of the function of HMGB1, a danger molecule in the pathogenesis of preeclampsia.


The Value of Diversity, Equity, and Inclusion: Race and Ethnicity Affecting Patients.
Patient race and ethnicity are important factors in health-care inequity, including care for the patient with hand and upper extremity pathologic condition. Physician diversity has been shown to promote better access, improve health-care quality, and improve satisfaction for underserved populations. Concordance, most often defined as a similarity or shared identity between physician and patient, has been shown to have a positive influence on health-care disparities. Although diversity among Hand surgeons is increasing, it is not matching the diversity of the population as a whole. It is imperative that we work to increase and maintain diversity in order to provide the best care for our patients.


Fluorescent probes for adenosine receptors: synthesis and biology of N6-dansylaminoalkyl-substituted NECA derivatives.
New fluorescent ligands for adenosine receptors are described; these compounds were obtained by the insertion, in the N6 position of NECA (a potent adenosine agonist), of dansylaminoalkyl moieties with alkyl spacers of increasing carbon chain length (from 3 to 12). Among them, the compound with a C6 alkyl spacer proved to be the most interesting one, showing a marked selectivity for the A1 receptor subtype; furthermore, in fluorescence microscopy assays it proved to be able to visualize and localize this receptor subtype at the level of the molecular layer of the rate cerebellar cortex.


Stereoselective synthesis of 11Z-9-demethyl-9-benzyl- and 9-phenyl-retinals and their interaction with bovine opsin.
11Z-9-Demethyl-9-benzyl- and 9-phenyl-retinals were synthesized stereoselectively from the beta-ionone analog-tricarbonyliron complexes and their interaction with bovine opsin was investigated.


Predictor factors affecting emotional and behavioral problems in school-aged (6-12 years) children during the COVID-19 pandemic: a cross-sectional study.
The prolonged outbreak of COVID-19 has caused psychological problems in the community, especially in children. Given that limited studies have been conducted on this vulnerable group in Iran, we conducted this study to determine the predictor factors affecting emotional and behavioral problems in school-aged (6-12 years) children during the COVID-19 pandemic. We conducted a cross-sectional study on 322 mothers of elementary school-aged children (6-12 years) from April 21 to June 21, 2021, in Karaj, Alborz, Iran. Sociodemographic checklist, socioeconomic status scale (SES), Depression, Anxiety, and Stress Scale (DASS-21), Corona Disease Anxiety Scale (CDAS), and the Rutter Children's Behavior Questionnaire (RCBQ) were used to evaluate the children's behavioral symptoms, the mental health of their mothers, and sociodemographic factors. In total, 17.7% of children (male = 27.0%, female = 11.7%) had behavioral problems. Results showed income (p-value = 0.007, 95%CI (-3.85- -0.607)), and physical activity of the child (p-value = 0.026, 95%CI (-1.03- -0.067)), were indirectly associated with children's behavioral symptoms. Having underlying disease (p-value = 0.00, 95%CI (1.712-5.949)), breastfeeding (p-value = 0.027, 95%CI (0.335-5.61)), corona-related anxiety (p-value = 0.00, 95%CI (0.158-0.318)), and DASS score (p-value = 0.00, 95%CI (0.149-0.334)) in the mothers, as well as male gender (p-value = 0.003, 95%CI (0.724-3.471)) were directly associated with children's behavioral symptoms. The most factors involved in the behavioral symptom score of children were corona-related anxiety (β = .298), DASS (β = 0.273), underlying disease of mothers (β = 0.163), income (β = -0.154), child's gender (β = 0.142) and physical activity (β = -0.101), and breastfeeding (β = 0.099) respectively. Study findings showed that some factors affect the emotional and behavioral problems of school-aged (6-12 years) children during the COVID-19 pandemic. These data may help future researchers and policymakers with early intervention.


COPD burden on sexual well-being.
Sexual function is often affected in patients suffering from chronic diseases especially chronic obstructive pulmonary disease (COPD). However, the effect of COPD on sexual satisfaction is underappreciated in clinical practice. The aim of this study is to evaluate the impact of COPD on patient's sexuality and the explanatory variables of sexual dissatisfaction. Questionnaires were emailed to participants and they submitted their responses on the Santé Respiratoire France website. Data about sexual well-being (Arizona Sexual Experience Scale, ASEX), Quality of life (VQ11), anxiety, depression (Hospitalized anxiety and depression, HAD) and self-declared COPD grade were collected. Seven hundred and fifty one subjects were included and were characterized as follows: women-51%, mean age-61 years, in a couple-62% and 70%-retired. Every grade of COPD was represented. Out of 751 participants, 301 participants (40%) had no sexual activity and 450 (60%) had sexual activity. From the 450 participants, 60% needed to change their sexual life because of their disease (rhythm, frequency and position). Subjects often used medications to improve sexual performance (43% used short-acting bronchodilator and 13% -specific erectile dysfunction drugs). ASEX questionnaire confirmed patients' dissatisfaction (diminution of sexual appetite for 68% and sexual desire for 60%) because of breathlessness and fatigue. Eighty one percent of the responders had an altered quality of life (VQ11 mean score 35) and frequent suspected anxiety or depression (HAD mean score 10.8). Ninety percent declared that sexual dysfunction had never been discussed by their doctors, while 36% of patients would have preferred to undergo a specialized consultation. Sexual dysfunction is frequent among COPD patients and leads to an altered well-being, however being a cultural taboo, it remains frequently neglected. Sexual guidance should be a part of patient's consultations improve quality of sexual life.


Recombinant human erythropoietin has little influence on megakaryocytopoiesis in mice.
The availability of a preparation of recombinant human erythropoietin (rEp) prompted us to investigate the role of Ep in the regulation of megakaryocytopoiesis in mice, using experimental procedures by which the effects on the mitotic and post-mitotic compartment of megakaryocytes could be evaluated separately. In agar cultures of murine bone marrow cells, either serum-depleted or serum-supplemented, rEp (0.1-2 U/ml) did not stimulate megakaryocyte colony formation and when it was added to suboptimal amount of spleen cell-conditioned medium (SCM), it failed to show a significant synergistic activity. On the contrary, rEp increased the number of megakaryocytic colonies developed from splenic precursors in the presence of suboptimal amounts of SCM, although it was unable per se to stimulate colony formation. The effects of rEps on megakaryocyte maturation and platelet production were studied in vivo evaluating the incorporation of 75Se-selenomethionine into platelets, the platelet count and platelet size, and the number of megakaryocyte precursors (small acetylcholinesterase positive cells, sAchE) in the bone marrow of mice injected with 1-8 U of rEp. No modification of these parameters was found in comparison with control mice. On the other hand, rEp increased the number of recognizable splenic megakaryocytes in a dose-dependent fashion. These data suggest that rEp has little influence on megakaryocytopoiesis, at least at the doses we used and which are known to elicit a maximal response of erythropoiesis. However, a subset of megakaryocytes with particular kinetic properties, such as those in the spleen of mice, may be responsive to relatively high doses of rEp. The significance of this observation in the overall regulation of megakaryocytopoiesis remains to be determined.


Individual or combinational use of phytase, protease, and xylanase for the impacts on total tract digestibility of corn, soybean meal, and distillers dried grains with soluble fed to pigs.
This study was to evaluate the effects of individual or combinational use of phytase, protease, and xylanase on total tract digestibility of corn, soybean meal, and distillers dried grains with soluble (DDGS) fed to pigs. Each experiment had four 4×4 Latin squares using 16 barrows. Each period had 5-d adaptation and 3-d collection. All experiments had: CON (no enzyme); Phy (CON+phytase); Xyl (CON+xylanase); Pro (CON+protease); Phy+Xyl; Phy+Pro, Xyl+Pro, Phy+Xyl+Pro. Each Latin square had 'CON, Phy, Xyl, and Phy+Xyl'; 'CON, Phy, Pro, and Phy+Pro'; 'CON, Pro, Xyl, and Xyl+Pro'; and 'Phy+Xyl, Phy+Pro, Xyl+Pro, Phy+Xyl+Pro'. The digestible energy (DE), metabolizable energy (ME), and nitrogen retention (NR) of corn were not affected by enzymes but the apparent total tract digestibility (ATTD) of phosphorus (P) was improved (p<0.01) by Phy. The DE and ATTD dry matter (DM) in soybean meal were increased (p<0.05) by Phy+Pro and the ATTD P was improved (p<0.01) by Phy, Phy+Pro, and Phy+Xyl. The DE, ME, and ATTD DM in DDGS were improved (p<0.05) by Phy+Xyl and the ATTD P was improved (p<0.01) by Phy, Phy+Pro, and Phy+Xyl. Phytase individually or in combination with xylanase and protease improved the Ca and P digestibility of corn, soybean meal, and DDGS, from the hydrolysis of phytic acid. The supplementation of protease was more effective when combined with phytase and xylanase in the soybean meal and DDGS possibly due to a higher protein content in these feedstuffs. Xylanase was more effective in DDGS diets due to the elevated levels of non-starch polysaccharides in these feedstuffs. However, when xylanase was combined with phytase, it demonstrated a higher efficacy improving the nutrient digestibility of pigs. Overall, combinational uses of feed enzymes can be more efficient for nutrient utilization in soybean meal and DDGS than single enzymes.


Novel Mechanistic Insights into the Anti-cancer Mode of Arsenic Trioxide.
Arsenic, a naturally-occurring toxic element, and a traditionally-used drug, has received a great deal of attention worldwide due to its curative anti-cancer properties in patients with acute promyelocytic leukemia. Among the arsenicals, arsenic trioxide has been most widely used as an anti-cancer drug. Recent advances in cancer therapeutics have led to a paradigm shift away from traditional cytotoxic drugs towards the targeting of proteins closely associated with driving the cancer phenotype. Due to the diverse anti-cancer effects of ATO on different types of malignancies, numerous studies have made efforts to uncover the mechanisms of ATO-induced tumor suppression. From in vitro cellular models to studies in clinical settings, ATO has been extensively studied. The outcomes of these studies have opened doors to establishing improved molecular-targeted therapies for cancer treatment. The efficacy of ATO has been augmented by combination with other drugs. In this review, we discuss recent arsenic-based cancer therapies and summarize the novel underlying molecular mechanisms of the anti-cancer effects of ATO.


The contribution of a murine CNS-TB model for the understanding of the host-pathogen interactions in the formation of granulomas.
Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB, characterized morphologically by brain granulomas and tuberculous meningitis (TBM). Experimental strategies for the study of the host-pathogen interaction through the analysis of granulomas and its intrinsic molecular mechanisms could provide new insights into the neuropathology of TB. To verify whether cerebellar mycobacterial infection induces the main features of the disease in human CNS and better understand the physiological mechanisms underlying the disease, we injected bacillus Calmette-Guerin (BCG) into the mouse cerebellum. BCG-induced CNS-TB is characterized by the formation of granulomas and TBM, a build up of bacterial loads in these lesions, and microglial recruitment into the lesion sites. In addition, there is an enhanced expression of signaling molecules such as nuclear factor-κB (NF-κB) and there is a presence of inducible nitric oxide synthase (iNOS) in the lesions and surrounding areas. This murine model of cerebellar CNS-TB was characterized by cellular and biochemical immune responses typically found in the human disease. This model could expand our knowledge about granulomas in TB infection of the cerebellum, and help characterize the physiological mechanisms involved with the progression of this serious illness that is responsible for killing millions people every year.


Do proton pump inhibitors increase the risk of dementia? A systematic review, meta-analysis and bias analysis.
Previous studies on the association between proton pump inhibitor (PPI) intake and the increased risk of dementia has shown discrepancies in their conclusions. We aimed to provide updated evidence based on extensive bias assessments and quantitative sensitivity analyses. We searched the databases PubMed, EMBASE, SCOPUS, CENTRAL and clinicaltrials.gov for prospective studies that examined an association between PPI use and dementia, up to February 2022. Each study was assessed using the Cochrane risk of bias assessment tools for non-randomized studies of interventions (ROBINS-I) or randomized trials (RoB2). Pooled risk ratios (RRs) and 95% prediction intervals were computed using random-effects models. Sensitivity analyses were adjusted for small-study bias. We included nine observational studies with 204 108 dementia cases in the primary analysis on the association between PPI use vs. non-use and dementia, and the RR was 1.16 (95% CI = 1.00; 1.35). After adjusting for small-study bias by Copas selection model and Rücker's shrinkage procedure, the RR was 1.16 (1.02; 1.32) and 1.15 (1.13; 1.17), respectively. A subgroup analysis of PPI use vs. non-use regarding Alzheimer's disease risk yielded an RR of 1.15 (0.89; 1.50). The secondary analysis on the risk of dementia by use of PPI vs. histamine-2 receptor antagonist showed an RR of 1.03 (0.66; 1.62). This meta-analysis provided no clear evidence for an association between PPI intake and the risk of dementia. Due to discrepancies in sensitivity analyses, however, some risk of dementia by PPI use cannot be ruled out. Since an unequivocal conclusion is still pending, further research is warranted.


High-output soft-contact fiber-structure triboelectric nanogenerator and its sterilization application.
Infectious diseases are spreading rapidly with the flow of the world's population, and the prevention of epidemic diseases is particularly important for public and personal health. Therefore, there is an urgent need to develop a simple, efficient and non-toxic method to control the spread of bacteria and viruses. The newly developed triboelectric nanogenerator (TENG) can generate a high voltage, which inhibits bacterial reproduction. However, the output performance is the main factor limiting real-world applications of TENGs. Herein, we report a soft-contact fiber-structure TENG to avoid insufficient friction states and to improve the output, especially at a high rotation speed. Rabbit hair, carbon nanotubes, polyvinylidene difluoride film and paper all contain fiber structures that are used to guarantee soft contact between the friction layers and improve the contact state and abrasion problem. Compared with a direct-contact triboelectric nanogenerator, the outputs of this soft-contact fiber-structure TENG are improved by about 350%. Meanwhile, the open-circuit voltage can be enhanced to 3440 V, which solves the matching problems when driving high-voltage devices. A TENG-driven ultraviolet sterilization system is then developed. The bactericidal rate of this sterilization system can reach 91%, which significantly reduces the risk of disease spread. This work improves a forward-looking strategy to improve the output and service life of the TENG. It also expands the applications of self-powered TENG sterilization systems.


Person-centered care for family caregivers of people living with dementia: Co-designing an education program for the healthcare workforce.
Recent research recommends the healthcare workforce receive competency-based education to identify, assess, support and partner with family-caregivers [FCGs} across the care trajectory.[1 2] Although the risk of FCG anxiety, burden, and loneliness to FCG's wellbeing is widely documented, typically education has been targeted towards FCG's to increase their care skills rather to educate healthcare providers to support FCG's caregiving and wellbeing.[3] OBJECTIVES: We will present the co-design process used to create a competency-based education program for the healthcare workforce that ensures a person-centered focus on FCGs and introduce our Health Workforce Caregiver-Centered Care Education focused on dementia. Co-design is the act of creating with stakeholders to ensure the results meet their needs and are usable. We began by coining the concept "caregiver-centered care," defining it as: a collaborative working relationship between families and healthcare providers aimed at supporting FCGs in their caregiving role, decisions about services, care management, and advocacy [4 5] . From this definition, and working with multi-level interdisciplinary stakeholders we designed[6] and validated[7] a Caregiver-Centered Care Competency Framework in a Modified Delphi Process. Stakeholders (n= 101) including FCGs, health providers, policy makers, community organizations, research team, script writer, and educational designers then used effective practices for dementia education for the health workforce [8-11] to co-design the first or 'foundational' level of a Caregiver Centered Care education program. Teaching and learning resources include six competency-aligned educational modules with videos and interactive exercises that encourage reflection. With the COVID-19 pandemic, we moved the education online (caregivercare.ca). In the first two months online, November 9, 2020-January 9, 2021, 352 healthcare providers completed the education. To date, learners' qualitative evaluations have been positive, "Very good information for professionals working with caregivers; especially relevant to homecare, geriatricians, allied health, and others working within the Seniors' Health realm. Engaging format that really evokes empathy for caregivers." We continue to use mixed methods to evaluate the Caregiver-Centered Care Education, for acceptability and effectiveness, in five care contexts (primary, acute, home, supportive living, long-term care). We expect that our education will support caregiver-centered care in all settings providing dementia-related care.