Diminished hypotensive response to isoproterenol in streptozotocin-diabetic rats.
1. The cardiovascular reactivity of streptozotocin-diabetic rats has been evaluated with isoproterenol (ISO), a strong beta-adrenergic agonist able to produce, at large dose, myocardial infarction. 2. In the basal state, diabetic rats presented significantly lower heart rate (P less than 0.001), a decreased systolic (P less than 0.05) and an unaltered diastolic blood pressure compared to non-diabetics. 3. Following ISO stimulation, the chronotropic response was similar in both groups of rats, while the fall in systolic and diastolic pressure was markedly reduced compared to those of non-diabetic rats (P less than 0.001). 4. These results suggest that the vasodilation capacity of diabetic rats is diminished.


A painful purgatory: grief and the Nicaraguan mothers of the disappeared.
In Latin America the past two decades have been marked by low-intensity conflicts, state-sponsored violence, and the creations of 'cultures of terror'. This research, conducted in Managua, Nicaragua during 1991-92 examines the impact of political violence on a small group of women whose relatives were 'disappeared' during the Contra War. I discuss the lack of discourse about the disappeared and suggest possible reasons for this silence in the body politic, the community and the family. The historical routinization of violence against the Nicaraguan poor and the continuing socio-political instability within the country present specific challenges to the healing processes of the Nicaraguan Mothers of the Disappeared. This article discusses some of the ways that these mothers challenge the collective silence and confront the public amnesia about what happened during the decade of war.


The specificity of somatic and metabolic Taenia taeniaeformis preparations in murine metacestode infections.
Excretory-secretory and somatic preparations of Taenia taeniaeformis contained shared immunologically-active components although immunoelectrophoresis indicated that the major antigen present in the excretory-secretory preparation was only a minor component of the somatic preparation. Both antigens gave similar immunoelectrophoretic reactions with sera from mice infected with either T. taeniaeformis or Taenia crassiceps, but there was evidence from the results using the ELISA technique that the excretory-secretory components showed more species specificity than those of somatic origin.


Letter to the Editor Re: Andrew Turner, Emily R. Kearl, Kevin R. Solman Lead and other toxic metals in playground paints from South West England Science of the Total Environment 544 (2016) 460-466.
Turner's paper emphasizes "oral bioaccessibility" instead of focusing solely on total lead content. There is no evidence that solubility testing for lead levels in paint correlates with absorption or blood lead levels in exposed children. There are many considerations in determining exposure hazards to paint that are not evaluated in assessing solubility. Although we strongly support the conclusions and recommendations of the study, we are concerned that by reporting "oral bioaccessibility" others will focus on solubility in developing regulatory standards for lead levels in paint or in conducting exposure assessments. Standards for lead in paint should continue to be based on total lead content, not "oral bioaccessibility."


Long-term results of esotropia surgery in children with developmental delay.
To assess the long-term results of esotropia surgery in children with developmental delay who were operated on with reduced surgical dosages. This was a retrospective analysis of children with developmental delay who had undergone surgery for esotropia during a 16-year period. The pre- and postoperative angle of deviation was calculated for each subject as the mean of distant and near angles measured by a cover test or the Krimsky measurement. The main outcome measure was surgical success, categorized as esotropia or exotropia of ≤ 10(Δ). The chart review identified 24 children who met inclusion criteria, with a mean age of 2.8 ± 2.5 years (range, 0.8-10 years). The mean angle of preoperative esotropia was 49.8(Δ) ± 13.3(Δ). All patients had bilateral medial rectus muscle recessions, with a mean surgical dosage of 5.1 ± 0.7 mm per muscle, on average 0.75 mm less than the standard amount. The average postoperative follow-up was 5.3 ± 3 years (range, 1-13 years). Surgical success was achieved in 9 of 24 children (37.5%) after one operation. Among the 15 failures, 10 (66.6%) were undercorrected, and 5 (33.3%) developed consecutive exotropia. Of these, 8 (53%) agreed to a second procedure. The overall surgical success rate for all patients after all procedures was 63%. Although the initial success rate is low with reduced surgical amounts in children with developmental delays, and some children become exotropic on long-term follow-up, satisfactory results may be achieved with additional procedures.


Guideline - Adherence in advanced stage head and neck cancer is associated with improved survival - A National study.
Understanding the prevalence of guideline non-adherence among patients with advanced head and neck cancer (HNC) and its impact on survival may facilitate increased adherence. Our objective was to perform a detailed analysis of overall National Comprehensive Care Network (NCCN) guideline adherence in a national cohort. Using the National Cancer Database, we analyzed site-specific NCCN guideline adherence for treatment of 100,074 overall stage III and IVA HNC patients from 2004 to 2013. Main outcomes were guideline adherence rates and overall survival (OS). Adherence was categorized by treatment: surgery/ radiation. Reasons were categorized as: (1) high risk; (2) refusal; (3) not planned. After exclusion, the care of 25,620 patients was defined as non-adherent (25.6%), yet adherence rates significantly improved across the study's years. After multivariate analysis, non-adherence was associated with age ≥ 65, female gender, black race, comorbidity score ≥ 1, insurance status, clinical staging, primary site, and facility type. Patients not managed according to NCCN guidelines had a significantly reduced OS compared with patients treated on-guideline (hazard ratio (HR) = 1.51 (95 %CI 1.48-1.54), p < 0.001). 'Not planned' patients had reduced OS when compared to adherent patients (HR = 1.27 (95 %CI 1.23-1.30), p < 0.001). Off-guideline treated patients due to 'risk factors' had a decrease in overall survival (OS) compared with other reasons (p < 0.001 for all). Despite improvement over time, non-adherence to NCCN guidelines for advanced stage HNC remains high. Non-adherence is associated with decreased OS, regardless of the reason. Despite concerns from both patient and physician, efforts should be made to increase guideline awareness and adherence.


Impaired fetal thymic growth precedes clinical preeclampsia: a case-control study.
In preeclampsia the maternal adaptive immune system undergoes specific changes, which are different from the physiological processes associated with healthy pregnancy. Whether preeclampsia also affects the fetal immune system is difficult to investigate, due to limited access to the fetus. We hypothesized that if preeclampsia affects the fetal adaptive immune system this might be associated with early changes in thymic growth. In this case-control study, 53 preeclamptic and 120 healthy control pregnancies were matched for maternal age, gestational age and smoking. Fetal thymus diameter was measured as the greatest width perpendicular to a line connecting sternum and spine based on ultrasound images taken at 17-21 weeks gestation. Independent of fetal and maternal anthropometric measures, thymuses were found to be smaller in preeclamptic pregnancies than healthy controls (16.2 mm versus 18.3 mm, respectively, mean difference=2.1 mm, 95% CI: 0.8-3.3, p<0.001), and the odds of developing preeclampsia was estimated to be 0.72 (95% CI: 0.60-0.86, p<0.001) lower for each 1 mm increase in thymus diameter. There was no correlation between the onset of preeclampsia and fetal thymus size. This is the first study to suggest that fetal thymus growth is reduced before the clinical onset of preeclampsia and precedes any described fetal anomalies or maternal immunological changes associated with preeclampsia. We propose that the fetal adaptive immune system is either passively affected by maternal processes preceding clinical preeclampsia or is actively involved in initiating preeclampsia in later pregnancy.


High poly ε-caprolactone biodegradation activity by a new Acinetobacter seifertii isolate.
Poly(ε-caprolactone; PCL) is an attractive biodegradable polymer that has been increasingly used to solve environmental problems caused by plastic wastes. In the present study, 468 bacterial isolates were recovered from soil samples and screened for PCL degradation activity. Of the isolates, 37 (7.9%) showed PCL depolymerase activity on PCL agar medium, with the highest activity being by isolate S22 which was identified using 16S rRNA and rpoB gene sequencing as Acinetobacter seifertii. Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed the degradation of PCL films after treatment with A. seifertii S22. The PCL depolymerase activity of A. seifertii S22 relied on the activity of esterase which occurred at an optimum temperature of 30-40 °C. The highest PCL depolymerase activity (35.5 ± 0.7 U/mL) was achieved after culturing A. seifertii S22 for 6 h in mineral salt medium (MSM) containing 0.1% Tween 20 and 0.02% ammonium sulfate as the carbon and nitrogen sources, respectively, which was approximately 20-fold higher than for cultivation in MSM supplemented with 0.1% PCL as sole carbon source. The results suggested that A. seifertii S22 or its enzymes could be used for PCL bioplastic degradation.


Identification of three new HLA class I alleles: HLA-B*50:73, -C*08:218 and -C*15:229.
Characterization of three new HLA class I alleles, B*50:73, C*08:218 and C*15:229.


Implant supported fixed partial dentures survival rate high, but biological and technical complications common.
PubMed (1966-April 2004) provided the primary data source along with the bibliographies from identified articles and reviews. Manual search of eight relevant journals (published 2001-2003) provided a further source of data. As there were no randomised controlled trials comparing implant therapy with conventional reconstructive dentistry, English language prospective and retrospective cohort studies were selected if; they had a mean follow-up of >/=5 years; included patients who were clinically examined at follow-up; reported details on suprastructures and described at least one-third of reconstructions as fixed partial dentures (FPDs). Two independent reviewers screened articles for inclusion. Disagreements were resolved by discussion and agreement determined by kappa. Data were extracted on the survival proportions of the reconstructions and on biological and technical complications. Biological complications included disturbances in the function of the implant characterized by a biological process affecting the supporting tissues. Technical complications denoted mechanical damage of implants, implant components, or the suprastructures. The number of events for all categories was identified and the corresponding total exposure time of the reconstruction calculated. Failure and complication rates were calculated by dividing the number of events by the total exposure time. Twenty-one studies of implant supported FPDs, reporting on 16 patient cohorts were included. Of the studies, 16 were prospective and five retrospective. A total of 1336 FPDs supported by 3578 oral implants were involved. Meta-analyses gave an estimated implant survival of 95.4% (95% CI 93.9-96.5) after 5 years and 92.8% (95% CI 90-94.8) after 10 years. Implant failure rate was 48% lower (P=0.006) in the more recent studies. The estimated survival for the FPDs was 95% (95% CI 92.2-96.8) after 5 years and 86.7% (95% CI 82.8-89.8) after 10 years. Four studies provided information on the number of patients free from complications - after 5 years 61.3% (95% CI 55.3-66.8) had suffered no minor or major complications. A random effects Poisson model revealed the rate of biological complications for patients treated with implant supported FPDs to be 8.6% (95% CI 5.1-14.1) after 5 years. For technical complications the cumulative 5 year complication rate varied from 0.4% for implant fracture to 13.2% for veneer fracture. Although survival rate for implant supported FPDs is high, biological and technical complications are relatively common.


K-wire assisted split-thickness skin graft harvesting from the anterior trunk.
Split thickness skin graft (STSG) harvesting from the anterior chest and abdominal wall skin is quite a difficult process. The main reason for the difficulty to perform this process is the unsuitable anatomic characteristics of the anterior trunk, such as irregular wavy-like surface over the ribs and lax abdominal wall skin resulting in collapse due to lack of adequate underneath supporting structures when a downward force is applied by the skin graft dermatome. Lower extremity and especially the thigh are generally chosen as the donor site where the STSGs are easily harvested from. However, extensive lower extremity burns, with or without other region burns, preclude harvesting auto STSGs from this invaluable anatomic site. We harvested K-wire assisted STSGs from the anterior chest and abdominal wall skin of 7 patients with lower extremity burns and also a patient that sustained motor vehicle collision. We encountered no problems in any of our patients both intra and postoperatively by using K-wire assisted STSG harvesting. All of the STSGs donor sites healed uneventfully without complications. In our opinion, K-wire assisted STSG harvesting must always be in the tool-box of any surgeon who deals with extensive burns with or without lower extremity burns and extensive traumas of lower extremities.


Neurotrophin-3 reduces apoptosis induced by 6-OHDA in PC12 cells through Akt signaling pathway.
Previous work has demonstrated that 6-hydroxydopamine (6-OHDA) induces apoptosis in PC12 cells. The goal of the present study was to investigate the mechanisms underlying the protection by neurotrophin-3 (NT-3) against 6-OHDA-induced apoptosis in PC12 cells. Treatment of PC12 cells with 6-OHDA resulted in activation of caspase-3 and subsequent apoptosis, as detected by TUNEL staining. In addition, Akt phosphorylation was decreased following 6-OHDA treatment. Pretreatment with NT-3 reduced the percentage of apoptotic cells and caspase-3 activity induced by 6-OHDA and suppressed the cleavage of caspase-3 and Poly(ADP-ribose) polymerase (PARP) with a significant decrease in cell viability. Moreover, Akt phosphorylation was enhanced and 6-OHDA-induced chromatin condensation was suppressed by NT-3. Such NT-3-evoked suppression in chromatin condensation was reversed by anti-TrkA antibody receptor blockade. Further study revealed that LY294002, an inhibitor of PI3-kinase (a molecule upstream of Akt), enhanced 6-OHDA-induced apoptosis. These data indicate that NT-3 prevents 6-OHDA-induced apoptosis in PC12 cells via activation of PI3-kinase/Akt pathway.


An investigation of machine learning algorithms for prediction of lumbar disc herniation.
The prevalence of lumbar disc herniation (LDH), which makes patients' daily activities more difficult and reduces their quality of life, has tended to increase recently. Many risk factors associated with LDH have been reported. In this study, LDH was predicted using machine learning techniques using measures of the lumbar paraspinal muscles, lumbar vessels cross-sectional area (CSA), and lumbar sagittal curve. Three hundred and forty-four individuals' MR scans were prospectively enrolled (264 with LDH and 80 healthy). Predictive factors were the lumbar sagittal curve and the cross-sectional areas of the lumbar paraspinal muscles and vessels from sagittal and axial MR images. The measurements have been analyzed via ten different and most common machine learning algorithms by considering a comprehensive parameter tuning and cross-validation process. The variable importance results have been also presented. XGBoost algorithm among all algorithms has provided the best results in terms of different classification metrics including f-score ([Formula: see text]), AUC ([Formula: see text]), accuracy ([Formula: see text]), and kappa ([Formula: see text]). The findings of this study demonstrated that cross-sectional areas of the quadratus lumborum and abdominal aorta can be utilized as a reliable indicator of LDH. Consequently, the developed model and the variables found to be important may guide to healthcare professionals to make more accurate and effective decisions in terms of prediction the LDH.


Photoreduction of the fluorescent dye 2'-7'-dichlorofluorescein: a spin trapping and direct electron spin resonance study with implications for oxidative stress measurements.
The photoreduction of 2'-7'-dichlorofluorescein (DCF) was investigated in buffer solution using direct electron spin resonance (ESR) and the ESR spin-trapping technique. Anaerobic studies of the reaction of DCF in the presence of reducing agents demonstrated that during visible irradiation (lambda > 300 nm) 2'-7'-dichlorofluorescein undergoes one-electron reduction to produce a semiquinone-type free radical as demonstrated by direct ESR. Spin-trapping studies of incubations containing DCF, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and either reduced glutathione (GSH) or reduced NADH demonstrate, under irradiation with visible light, the production of the superoxide dismutase-sensitive DMPO/*OOH adduct. In the absence of DMPO, measurements with a Clark-type oxygen electrode show that molecular oxygen is consumed in a light-dependent process. The semiquinone radical of DCF, when formed in an aerobic system, is immediately oxidized by oxygen, which regenerates the dye and forms superoxide.


Inhibition of morphine tolerance by spinal melanocortin receptor blockade.
Chronic use of morphine is accompanied by the development of morphine tolerance, which is one of the major problems associated with opiate treatment. Possible modulation of opioid effects by melanocortin receptor ligands has been recently demonstrated. Therefore, we investigated the influence of repeated intrathecal injection of a melanocortin receptor antagonist (SHU9119, JKC-363) on the development of morphine tolerance as measured by tail-flick test. It was also examined whether a single i.t. SHU9119 and JKC-363 administration could counteract the loss of analgesic potency of morphine in morphine tolerant rats. We examined also the influence of chronic morphine administration on mu-opioid receptor (MOR) and melanocortin 4 receptor (MC4-R) mRNAs in the rat spinal cord and dorsal root ganglia (DRG) during morphine tolerance. Morphine treatment (10mg/kg, i.p. twice daily) over 8 days induced tolerance as reflected by a significant reduction of withdrawal latency from 181 to 25% above baseline in the tail-flick test. Repeated co-administration of morphine and SHU9119 or JKC-363, significantly prevented the development of morphine tolerance. A single administration of an MC4-R antagonist restored morphine analgesic potency in morphine tolerant rats. Using RT-PCR we demonstrated no changes in the spinal cord but there was a decrease in MOR and increase in MC4-R gene expression in the DRG of rats tolerant to morphine. These results suggest that MC4-R may be involved in the mechanisms of opioid tolerance and antagonists of this receptor may be a possible new target in the search for strategies preventing the development of opioid tolerance.


[The potential for enhancing the therapeutic efficacy of antitumor preparations].
Joint introduction of cytostatic antitumor drugs and dogfish liver extract into animals with experimental tumors was shown to increase the efficacy of drugs as revealed by the increase in life span of experimental animals.


End-user perspectives of two mHealth decision support tools: Electronic Community Case Management in Northern Malawi.
The introduction of a paper-based Community Case Management (CCM) in Malawi has contributed to a reduction of child morbidity and mortality rates. In addition, the introduction of electronic Community Case Management (eCCM) (smartphones with built in CCM apps) may help to reduce the under-five mortality rates even further. It is not uncommon for Apps with a similar area of interest to develop different features to assist the end users. Such differences between Apps may have a significant role to play in its overall adoption and integration. The purpose of this research was to explore end users perspectives of two eCCM decision support tools developed and implemented by the Supporting LIFE project (SL eCCM App) and D-Tree International's (Mangologic eCCM App)in Northern Malawi. A mixed methods approach was applied, involving a survey of 109 users (106 Health Surveillance Assistants (HSAs), and 3 Integrated Management of Childhood Il6lnesses (IMCI) coordinators). This was followed up with semi-structured interviews with 34 respondents (31 HSAs, and 3 IMCI coordinators). Quantitative data was analyzed using SPSS version 20 where descriptive statistics and Chi-Squared tests were generated. Qualitative data were analyzed based on thematic analysis. Participants reported that both Apps could assist the HSAs in the management of childhood illnesses. However, usability differed between the two apps where the Supporting LIFE eCCM App was found to be easier to use (61%) compared to the Mangologic eCCM App (4%). Both Apps were perceived to provide credible and accurate information. It is essential that the quality of the data within Mobile Health (mHealth) Apps is high, however even Apps with excellent levels of data quality may not succeed if the overall usability of the App is low. Therefore it is essential that the Apps has high levels of data quality, usability and credibility. The results of this study will help inform mobile Health (mHealth) App designers in developing future eCCM Apps as well as researchers and policy makers when considering the adoption of mHealth solutions in the future in Malawi and other LMICs.


Preparative chromatography of xylanase using expanded bed adsorption.
Expanded bed adsorption was used to purify a marketable xylanase often used in the kraft pulp bleaching process. Experiments in packed and expanded beds were carried out mainly to study the adsorption of xylanase on to a cationic adsorbent (Streamline SP) in the presence of cells. In order to study the presence of cells, a Bacillus pumilus mass (5% wet mass) was mixed with the enzyme extract and submitted to an expanded bed adsorption system. One xylanase was purified to homogeneity in the packed bed. However, the 5% cell content hampered purification.


Early Short Stimulation Modified Natural Cycle IVF With GnRH Agonist Trigger and In Vitro Maturation in a Woman with Polycystic Ovary Syndrome: A Case Report.
Gonadotropin-releasing hormone agonist (GnRHa) triggering of final oocyte maturation has been used successfully in GnRH antagonist IVF cycles. It has not been used to date in cycles in which immature oocytes are matured in vitro. We report here for the first time that GnRHa triggering in a variation on the modified natural IVF cycle can be used as a strategy in the treatment of infertility secondary to polycystic ovary syndrome. In this approach, follicles were stimulated with gonadotropins for three to five days when they were small, and triggering of ovulation occurred when the largest follicles were 10 to 12 mm in diameter. This was followed by retrieval of many immature oocytes that were matured in vitro and subsequently developed to form blastocysts that resulted in a live birth. This is the first human evidence that GnRHa triggering of ovulation can be used successfully when the aim is in vitro maturation of oocytes.


Ambulatory computer system for recording and controlling locomotion.
Description of an original miniature computer system capable of recording biomechanical parameters during locomotion, providing auditory signals which can be used in biofeedback locomotor learning, and triggering functional electrical stimulation of nerves and muscles at preselected moments in the locomotor cycle. The system, which is worn on the patient's back, is connected to appropriate gauges with which it is possible to measure knee angle and to record the time of heel contact with the ground. The relevant data are stored in the system memory and can be transferred to a microcassette and later displayed as a function of time on a video screen or printed on paper. The same data can be used on-line to provide a patient with a sound signal as a basis for biofeedback training. This kind of training has been successfully used to correct knee hyperextension during locomotion in hemiplegic patients. The system can also be used to trigger a stimulator and thus constitutes a valuable tool for investigations and treatments involving functional electrical stimulation. Many other applications may be developed, both in basic research and in various fields where motor training is required.


Dupilumab: A Review in Moderate to Severe Asthma.
Dupilumab (Dupixent®) is a fully human monoclonal antibody against the interleukin (IL)-4 receptor α subunit of IL-4 and IL-4/IL-13 receptor complexes. IL-4 and IL-13 are key cytokines in driving type 2 inflammation, a dominant and largely eosinophilic inflammatory pathway in asthma. Trials evaluating the efficacy of dupilumab in asthma include three pivotal, placebo-controlled, phase 3 or 2b trials of 24-52 weeks' treatment duration in patients aged ≥ 12 years with moderate-to-severe asthma (inadequately controlled with medium-to-high dose inhaled corticosteroids) or severe asthma [dependent on oral corticosteroids (OCS) for control]. In these studies, adding subcutaneous dupilumab (200 or 300 mg every 2 weeks) to background therapy was generally well tolerated and reduced the rate of severe asthma exacerbations, improved lung function, as well as asthma control and, where specified, health-related quality of life (HR-QOL), and enabled OCS maintenance doses to be reduced without impacting asthma control. Dupilumab displayed efficacy across various patient subgroups, although those with heightened type 2 immune activity, including elevated eosinophils and fractional exhaled nitric oxide, tended to have a more prominent treatment benefit. Dupilumab is consequently widely indicated (and a valuable treatment option) as an add-on therapy in patients aged ≥ 12 years who have severe/moderate-to-severe asthma with a type 2 inflammation/eosinophilic phenotype despite conventional treatments or have OCS-dependent asthma.


Neurophysiological profiles of responders and nonresponders to hypoglossal nerve stimulation: a single-institution study.
Hypoglossal nerve stimulation (HGNS) is an effective alternative treatment for obstructive sleep apnea that acts by opening the airway via selective stimulation of nerve fibers that innervate tongue muscles that protrude (genioglossus) and stiffen the tongue (transverse and vertical) while avoiding nerve fibers that innervate tongue muscles that retract the tongue (styloglossus and hyoglossus). There remains a subset of postoperative patients who fail to adequately respond to HGNS, in some cases due to mixed activation of muscles that simultaneously protrude and retract the tongue. This study aims to characterize the relationship between neurophysiological data from individual tongue muscle activation during intraoperative electromyographic recordings and postoperative apnea-hypopnea index responses to HGNS. A single-institution review of 46 patients undergoing unilateral HGNS implantation for obstructive sleep apnea. Patients were separated into responders and nonresponders through comparison of pre and postoperative apnea-hypopnea index. Neurophysiological data included electromyographic responses of the genioglossus, styloglossus/hyoglossus, intrinsic/vertical, and hyoglossus (neck) muscles to intraoperative stimulation using unipolar (- to - and o to o) and bipolar (+ to +) settings. The overall treatment success rate was 61% as determined by a postoperative apnea-hypopnea index < 20 events/h with a greater than 50% AHI reduction. We observed no statistically significant relationships between treatment response and individual muscle responses. However, we did note that increasing body mass index was correlated with worse postoperative responses. Although we noted a significant subgroup of clinical nonresponders to HGNS postoperatively, these patients were not found to exhibit significant inclusion of tongue retractors intraoperatively on neurophysiological analysis. Further research is needed to delineate additional phenotypic factors that may contribute to HGNS treatment responses. Wang D, Modik O, Sturm JJ, et al. Neurophysiological profiles of responders and nonresponders to hypoglossal nerve stimulation: a single-institution study. J Clin Sleep Med. 2022;18(5):1327-1333.


Computer simulation and modeling the metal to insulating transition of liquid mercury via pair, empirical, and many-body potentials.
In this study, Monte Carlo simulations were carried out to detect the metal-insulator transition in liquid mercury by changing the static properties at the microscopic scale. In the simulations pair, empirical, and many-body potentials govern metal-metal interactions in the canonical ensemble. The structural and thermodynamic changes over a wide temperature range from 773 to 1773 K are described in the first coordination shell and residual internal energy, respectively. The results reveal that during the simulated heating process, the properties undergo significant change at 1673 K, which is in connection with the metal-nonmetal transition in the liquid. These findings coincide with the experimental observations of this thermodynamic phenomenon. Notably, the free energy of association that renders the system to this thermodynamic state is estimated.


Finite element modeling mesh quality, energy balance and validation methods: a review with recommendations associated with the modeling of bone tissue.
The use of finite element models as research tools in biomechanics and orthopedics has grown exponentially over the last 20 years. However, the attention to mesh quality, model validation and appropriate energy balance methods and the reporting of these metrics has not kept pace with the general use of finite element modeling. Therefore, the purpose of this review was to summarize the current state of finite element modeling validation practices from the literature in biomechanics and orthopedics and to present specific methods and criteria limits that can be used as guidelines to assess mesh quality, validate simulation results and address energy balance issues. Of the finite element models reviewed from the literature, approximately 42% of them were not adequately validated, while 95% and 98% of the models did not assess the quality of the mesh or energy balance, respectively. A review of the methods that can be used to assess the quality of a mesh (e.g., aspect ratios, angle idealization and element Jacobians), measure the balance of energies (e.g., hour glass energy and mass scaling), and quantify the accuracy of the simulations (e.g., validation metrics, corridors, statistical techniques) are presented.


ICV vs. VMH injection of leptin: comparative effects on hypothalamic gene expression.
Leptin regulates feeding behavior and body weight by binding to its receptors localized in specific areas of the hypothalamus. Leptin injected twice daily for 4 days either into the right ventromedial hypothalamus (VMH) or into the right lateral cerebral ventricle (ICV) and using Real-Time Taqman RT-PCR, mRNA expression levels of selected genes in the arcuate nucleus-median eminence (ARC-ME) complex were quantitatively measured. Expression of selected genes from the ipsi- vs. contralateral VMH areas in rats injected with leptin into the VMH was also compared. VMH injections of leptin increased ARC-ME mRNAs of proopiomelanocortin (POMC), 27.3% (p<0.05); gamma-aminobutyric acid A receptor (GABRD), 89.3% (p<0.01); and thyrotropin-releasing hormone (TRH), 57.7% (p<0.01); and decreased janus kinase 2 (JAK2), 44.4% (p<0.001); suppressor of cytokine signaling 3 (SOCS3), 86.6% (p<0.001); signal transducer and activator of transcription 3 (STAT3), 46.8% (p<0.01); tyrosine hydroxylase (TH), 51.1% (p<0.001); prostaglandin E synthase (PTGES), 96.5% (p<0.001); tumor necrosis factor-alpha (TNF-alpha), 47% (p<0.01); and secretin, 55.4% (p<0.001). Only GABRD, 76.6% (p<0.01) and SCT, 64.9% (p<0.01) were up-regulated in the hypothalamic ARC-ME of rats with ICV leptin injections. VMH injections of leptin induced identical reductions in expression levels of CART, SOCS3, PTGES, and TNF-alpha in both VMH areas; except TH mRNA, whose expression was lowered ipsilaterally. Food intake, body and fat pad weights and serum insulin and leptin were also decreased in rats given leptin through VMH. This study suggests that leptin either unilateral exposure through VMH or bilateral exposure through ICV injections induces divergent ARC-ME gene profiles.


Successful management of breast cancer with liver metastases with medroxyprogesterone acetate treatment.
A 38-year-old woman with cancer in the left breast underwent standard radical mastectomy. The estrogen receptor and progesterone receptor status of the primary tumor was unknown. Ten years after the surgery, a metastatic liver tumor was detected, and chemoendocrine therapy, consisting of cyclophosphamide, epirubicin, 5-fluorouracil (CEF) and medroxyprogesterone acetate (MPA) was initiated. The metastatic liver tumor showed a partial response after 11 cycles of such chemoendocrine therapy. Subsequently, MPA alone was given daily as maintenance therapy, and the disease has remained stable for 6 years. For women with metastatic breast cancer, complete remission is uncommon, and stable disease is a reasonable goal of successful therapy. In this respect, chemoendocrine therapy with CEF and MPA, followed by MPA alone as maintenance therapy, was successful in the patient reported here. Importantly, the patient's quality of life has remained favorable for several years after the partial response was achieved.


Effectiveness of Combining Bevacizumab With First-Line Chemotherapy Regimens for Metastatic Colorectal Cancer in Real-World Practice.
Anti-vascular endothelial growth factor (VEGF) agents have shown clinical benefits against metastatic colorectal cancer (mCRC) when combined with cytotoxic chemotherapeutic drugs. Because randomized controlled trials have restrictive enrollment criteria, and because the participants typically do not resemble actual patients, we here investigated the efficacy of bevacizumab as part of a combination therapy for mCRC in a Korean real-world practice setting. We retrospectively evaluated 3748 patients with an initial diagnosis of mCRC or recurrent colorectal cancer with distant metastasis who received first-line chemotherapy in a tertiary cancer center. The primary study endpoint was overall survival. We used multivariate analysis using the Cox regression hazard model and propensity score matching (PSM) methods to adjust for any confounding clinicopathologic factors. Subgroup analysis was also performed for patients who did not receive local treatments for metastatic lesions before receipt of first-line chemotherapy. In an initial crude analysis, patients who received first-line FOLFOX or FOLFIRI showed better survival outcomes if these regimens were combined with bevacizumab (median overall survival, 3.5 vs. 2.3 years; hazard ratio [HR] = 0.66; 95% confidence interval [CI], 0.59-0.73; P < .001). However, Cox regression hazard model adjusted analysis using PSM methods revealed no significant survival differences between these groups (3.0 vs. 2.6 years; HR = 0.92; 95% CI, 0.79-1.07; P = .2612). We performed further survival analysis of 2814 patients with unresectable disease without metastasectomy who received metastatic radiofrequency ablation before chemotherapy. Cox regression and PSM analysis indicated that bevacizumab group showed better survival (HR = 0.82; 95% CI, 0.71-0.94; P = .005; and HR = 0.84; 95% CI, 0.71-0.99; P = .018). The addition of bevacizumab to a first-line chemotherapeutic regimen provides survival benefits in a real-world setting for mCRC patients who cannot undergo curative-intent local treatment for metastatic lesions.


Measuring influenza hemagglutinin (HA) stem-specific antibody-dependent cellular cytotoxicity (ADCC) in human sera using novel stabilized stem nanoparticle probes.
Generating vaccine that confers a complete protection is a major goal in designing a universal influenza vaccine. Currently, there is a considerable interest in the broadly neutralizing antibodies (bnAb) targeting the conserved HA stem region. These antibodies have been shown to activate cellular immune responses, such as ADCC, in addition to their neutralization activity. We had previously demonstrated that immunization with H1-based stabilized stem (SS) nanoparticles (np) protects against heterosubtypic lethal H5N1 challenge, despite the absence of detectable neutralizing activity. Utilizing these novel SS probes to develop an ADCC assay would help in understanding the mechanism of action of stem-specific antibodies, as well as evaluating future influenza vaccines. To develop a new protocol to assess the ADCC activity mediated by stem-directed antibodies in human sera using novel SS np probes. Human sera samples were screened for binding and ADCC activities to different influenza group 1 SS probes (H1, H2, and H5) using trimeric SS or multivalent SS-np (n = 8 trimers) formats. Initial screening revealed 63% (57/90) seroprevalence of anti-HA (H1) stem-epitope antibodies, as determined by the differential binding to HA SS and its corresponding epitope-mutant (Ile45Arg/Thr49Arg) probe. Using equimolar amounts, the multivalent presentation of HA SS on np induced significantly higher ADCC activity compared to the monovalent (trimer) SS probes (2-6 fold increase). Further, ADCC activity was similarly reported against different group 1 influenza subtypes: H1, H2, and H5. Importantly, ADCC was mediated mainly by antibodies targeting the bnAb-epitope on the HA stem. We report on an assay to measure stem-specific ADCC activity using SS np probes. Our results indicate high prevalence of HA-stem antibodies with cross-reactive ADCC activity. Such assay could be utilized in the assessment of next generation influenza vaccines.


[Treatment of the infected wound with exposed silver-ring vascular graft and delayed Thiersch method of skin transplant covering ].
Although the incidence of prosthetic infection is low (1%-6%), the consequences (limb loss or death) are dramatic for a patient, with high mortality rate (25%-75%) and limb loss in 40%-75% of cases. In case of Szilagyi's grade III infection, standard procedure consists of the excision of prosthesis and wound debridement. Alternative method is medical treatment. This is a case report of a patient with prosthetic infection of Silver-ring graft, used for femoropopliteal reconstruction, in whom an extreme skin necrosis developed in early postoperative period. This complication was successfully treated medically. After repeated debridement and wound-packing, the wound was covered using Thiersch skin graft.


Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates.
A widely applicable three-dimensional QSAR pharmacophore model for antimalarial activity was developed from a set of 17 substituted antimalarial indolo[2,1-b]quinazoline-6,12-diones (tryptanthrins) that exhibited remarkable in vitro activity (below 100 ng/mL) against sensitive and multidrug-resistant Plasmodium falciparum malaria. The pharmacophore, which contains two hydrogen bond acceptors (lipid) and two hydrophobic (aromatic) features, was found to map well onto many well-known antimalarial drug classes including quinolines, chalcones, rhodamine dyes, Pfmrk cyclin dependent kinase inhibitors, malarial FabH inhibitors, and plasmepsin inhibitors. The phamacophore allowed searches for new antimalarial candidates from multiconformer 3D databases and enabled custom designed synthesis of new potent analogues.


Therapeutic Effectiveness of Needle Injection Versus Needle-Free Jet Injector System for Botulinum Toxin Type A in Palmar Hyperhidrosis.
The most important problem with local injections of botulinum toxin type A (BTX-A) in palmar hyperhidrosis is pain during the injections. We evaluated therapeutic effectiveness and pain of local injections of BTX-A using needle-free direct administration system. We performed BTX-A local injection therapy using a conventional injection needle in the left hand and a needle-free direct administration system in the right hand. A reduction in the quantity of perspiration was observed 4 weeks after administration of both Needle and Needle-free BTX-A, and reduction was maintained throughout 28 weeks observation period. Both hyperhidrosis Disease Severity Scale scores and Dermatology Life Quality Index for hands treated with Needle BTX-A and hands treated with Needle-free BTX-A had decreased significantly by 4 weeks after treatment. Pain visual analog scale scores and the degree of pain were significantly lower in hands treated with Needle-free BTX-A than in hands treated with Needle BTX-A. When the trigger of the pressurized needle-free injector device is activated, the gas powered driving pressure propels BTX-A through an orifice (0.13 mm) about four times narrower than a 30 G needle at very high speed. As most pain occurs during the needle prick itself, the advantage of a small orifice coupled with high-speed penetration of BTX-A through the pressurized device results in reduced pain during administration. The needle-free direct administration system administers the injectate under the skin without a visible needle.


Anin vitro model for chick embryonic notochords.
A two step method to obtain mesenchymal free 3.5 day old chick embryonic notochordsin vitro is presented. 1.) Notochords are isolated by mechanical microdissection from the embryos below the head and above the leg-buds. 2.) The dissected notochords are trypsinized to eliminate contaminating mesenchymal cells, while the perinotochordal sheath (PNS) is retained. After isolation and trypsinization, notochords are cut in standard 8mm lengths, explantedin vitro and incubated at 37°C. Immediately before incubation and after 3 and 6 daysin vitro, notochords are fixed and stained to follow the morphological changes. The total DNA content of notochords is measured before and during maintenancein vitro to evaluate their metabolic activities. Results show that during thein vitro period, the isolated mesenchymal free notochordal fragments can conserve their characteristic architecture. The total DNA content measurements indicate proliferative activity and a high viability of the notochords in ourin vitro system. In the present study, an isolation andin vitro method is offered which might be an effective tool to study the metabolic activities of chick embryonic notochordsin vitro in comparison toin vivo behaviour, in order to study the underlying mechanism of notochord regression.


Effectiveness of intensive residential treatment (IRT) for severe, refractory obsessive-compulsive disorder.
The aim of this study was to determine the effectiveness of an innovative Intensive Residential Treatment (IRT) program for severe refractory Obsessive-Compulsive Disorder (OCD). No formalized OCD IRT outcome studies have been completed to date in North America. Subjects admitted to the Massachusetts General Hospital/McLean OCD Institute (OCDI) between February 1997 and June 2003 comprised the intent-to-treat sample. Measures of OCD severity, depression severity and psychosocial well-being were determined at admission, interim and discharge points, and were subsequently compared via t-tests using a last-observation-carried-forward approach. Initial OCD severity subgroups and treatment length subgroups were created and analyzed. Correlations and stepwise linear regressions were conducted to determine treatment length predictors. The sample of 403 individuals (58.7% male) had an average 66 day treatment length. Mean YBOCS scores decreased by 30.1%, from 26.6 (SD 6.1) at admission to 18.6 (SD 7.2) at discharge, reflecting a clinically meaningful improvement (p<0.001). Psychosocial functioning, depression severity scores and self-report global functioning ratings also indicated significant improvement. Subgroups with longer treatment lengths tended to have earlier ages of OCD onset and increased OCD severity scores at admission. IRT deserves recognition as a therapeutic approach for severe, refractory OCD. In the largest study to date for IRT significant improvements of OCD severity, depression severity and quality of life were determined. IRT should be considered prior to more invasive approaches for severe refractory OCD.


Dynamics of PEGylated-dextran-spermine nanoparticles for gene delivery to leukemic cells.
Leukemic cells are hard-to-transfect cell lines. Many transfection reagents which can provide high gene transfer efficiency in common adherent cell lines are not effective to transfect established blood cell lines or primary leukemic cells. This study aims to examine a new class of cationic polymer non-viral vector, PEGylated-dextran-spermine (PEG-D-SPM), to determine its ability to transfect the leukemic cells. Here, the optimal conditions of the complex preparation (PEG-D-SPM/plasmid DNA (pDNA)) were examined. Different weight-mixing (w/w) ratios of PEG-D-SPM/pDNA complex were prepared to obtain an ideal mixing ratio to protect encapsulated pDNA from DNase degradation and to determine the optimal transfection efficiency of the complex. Strong complexation between polymer and pDNA in agarose gel electrophoresis and protection of pDNA from DNase were detected at ratios from 25 to 15. Highest gene expression was detected at w/w ratio of 18 in HL60 and K562 cells. However, gene expression from both leukemic cell lines was lower than the control MCF-7 cells. The cytotoxicity of PEG-D-SPM/pDNA complex at the most optimal mixing ratios was tested in HL60 and K562 cells using MTS assay and the results showed that the PEG-D-SPM/pDNA complex had no cytotoxic effect on these cell lines. Spherical shape and nano-nature of PEG-D-SPM/pDNA complex at ratio 18 was observed using transmission electron microscopy. As PEG-D-SPM showed modest transfection efficiency in the leukemic cell lines, we conclude that further work is needed to improve the delivery efficiency of the PEG-D-SPM.


Food competition and social experience effects on V1a receptor binding in the forebrain of male Long-Evans hooded rats.
The present study investigated the effect of social status in Long-Evans hooded rats established during food competition on V(1a) vasopressin receptor (V(1a)R) binding in the lateral septum (LS), medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST), anterior hypothalamus (AH), and central/basolateral amygdala (CeB). Serum concentration of testosterone (T) and corticosterone (CORT) was also measured. In Experiment 1, thirty-two lever-trained weight-matched rat pairs were placed in operant chambers where a single bar press provided access to milk reinforcement. A dominant-subordinate relationship, determined by the duration of drinking, was evident in 88% of the pairs. Sixteen rats were lever-trained but did not interact and served as no-treatment (NT) controls. In the LS, V(1a)R binding in the subordinate (SUB) group was significantly higher than in the dominant (DOM) group. V(1a)R binding was significantly higher in the LS, BNST, CeB, and AH in the NT group than in the other groups. The levels of CORT and T were not affected significantly by group membership. Experiment 2 investigated whether the binding effect in the LS was related to differences in fluid consumption. The results did not indicate a significant effect of fluid consumption. In the rat, V(1a)R binding in several forebrain areas seems to be affected by brief periods of social interactions, and, in the LS, it also appears to be related to dominance status.


Oral and maxillofacial surgical services amid COVID-19 pandemic: perspective from Tanzania.
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 is a global pandemic that affects individuals from all walks of life. Considering that the virus can be passed on directly from person to person through respiratory droplets, contact, fomites, and saliva, the oral and maxillofacial surgeons are exposed to COVID-19 in their daily clinical duties. This is because of the nature of their work, which entails working within a short distance from patients' oral cavity and upper airway. As such, there is a need for having locally tailored standard guidelines for managing patients with oral and maxillofacial conditions during the COVID 19 pandemic in Tanzania.


Analysis of MYO7A in a Moroccan family with Usher syndrome type 1B: novel loss-of-function mutation and non-pathogenicity of p.Y1719C.
Mutations in the MYO7A gene are responsible for Usher syndrome type 1B (USH1B), the most common USH1 subtype, which accounts for the largest proportion of USH1 cases in most populations. Molecular genetic diagnosis in Usher syndrome is well established and identification of the underlying mutations in Usher patients is important for confirmation of the clinical diagnosis and genetic counseling. We analyzed a large consanguineous USH1 family from Morocco and linked the disease in this family to the MYO7A/USH1B locus. We identified the frequently described missense change p.Y1719C. In addition, we found the homozygous c.1687G>A mutation in the last nucleotide of exon 14, which is predicted to result in aberrant splicing and may lead to loss of MYO7A transcript. We further showed that p.Y1719C is not disease-causing but does represent a frequent polymorphism in the Moroccan population, with an estimated carrier frequency of 0.07. This finding has an important impact for molecular diagnosis and genetic counseling in USH1B families.


A novel beta-site amyloid precursor protein cleaving enzyme (BACE) isoform regulated by nonsense-mediated mRNA decay and proteasome-dependent degradation.
Proteolytic cleavage of amyloid beta-peptide (Abeta) from amyloid precursor protein (APP) is a key event in the pathogenesis of Alzheimer's disease. Beta-site amyloid precursor protein cleaving enzyme (BACE) cleaves the APP at the N-terminus of Abeta. We investigated whether particular stress conditions modify the expression and activity of BACE, and found that treatment of human neuroblastoma cells with protein synthesis inhibitors induced expression of a novel splice variant of BACE. This unusual transcript, I-127, is produced by usage of an internal splicing donor site in exon 3. The splicing event leads to a premature termination codon, as well as elimination of one of two conserved aspartic protease active sites, a transmembrane domain, and a C-terminal cytoplasmic tail from BACE. Low levels of this mRNA were found in the human brain. When expressed in cells, I-127 had no effect on Abeta secretion and was retained in the endoplasmic reticulum without propeptide removal. It was also unstable with a turnover t(1/2) of approximately 2h; normal BACE had a turnover t(1/2) of approximately 8h. Finally, I-127 was degraded in a proteasome-dependent manner. Thus, I-127 is regulated by both nonsense-mediated mRNA decay (NMD) and proteasome-dependent degradation.


Late gadolinium enhancement cardiac imaging on a 3T scanner with parallel RF transmission technique: prospective comparison of 3D-PSIR and 3D-IR.
To qualitatively and quantitatively compare different late gadolinium enhancement (LGE) sequences acquired at 3T with a parallel RF transmission technique. One hundred and sixty participants prospectively enrolled underwent a 3T cardiac MRI with 3 different LGE sequences: 3D Phase-Sensitive Inversion-Recovery (3D-PSIR) acquired 5 minutes after injection, 3D Inversion-Recovery (3D-IR) at 9 minutes and 3D-PSIR at 13 minutes. All LGE-positive patients were qualitatively evaluated both independently and blindly by two radiologists using a 4-level scale, and quantitatively assessed with measurement of contrast-to-noise ratio and LGE maximal surface. Statistical analyses were calculated under a Bayesian paradigm using MCMC methods. Fifty patients (70 % men, 56yo ± 19) exhibited LGE (62 % were post-ischemic, 30 % related to cardiomyopathy and 8 % post-myocarditis). Early and late 3D-PSIR were superior to 3D-IR sequences (global quality, estimated coefficient IR > early-PSIR : -2.37 CI = [-3.46 ; -1.38], prob(coef > 0) = 0 % and late-PSIR > IR : 3.12 CI = [0.62 ; 4.41], prob(coef > 0) = 100 %), LGE surface estimated coefficient IR > early-PSIR: -0.09 CI = [-1.11; -0.74], prob(coef > 0) = 0 % and late-PSIR > IR : 0.96 CI = [0.77; 1.15], prob(coef > 0) = 100 %). Probabilities for late PSIR being superior to early PSIR concerning global quality and CNR were over 90 %, regardless of the aetiological subgroup. In 3T cardiac MRI acquired with parallel RF transmission technique, 3D-PSIR is qualitatively and quantitatively superior to 3D-IR. • Late gadolinium enhancement is an essential part of a cardiac MRI examination • PSIR and IR sequences are the two possible options for LGE imaging • At 3T with parallel RF transmission, PSIR sequences are significantly better • One LGE sequence is sufficient, allowing an optimization of the acquisition time.


The effect of glucagon, norepinephrine, and dibutyryl cyclic AMP on cholesterol efflux and on the activity of 3-hydroxy-3-methylglutaryl CoA reductase in rat hepatocytes.
Incubation of rat hepatocytes for 3 hours in a sterol-free medium containing 1.5% albumin resulted in efflux of cellular sterol into the medium and an increased activity of 3-hydroxy-3-methylglutaryl CoA reductase. The secretion of cholesterol was inhibited when cells were incubated with glucagon, norepinephrine, or dibutyryl cyclic AMP. Glucagon and dibutyryl cyclic AMP also inhibited the induction of HMG-CoA reductase. Norepinephrine treatment resulted in a decrease in the synthesis and secretion of proteins but caused an increase in reductase activity. Insulin treatment had no effect either on reductase activity or on sterol efflux from rat hepatocytes.


The influence of tonsillectomy on obstructive sleep apnea children with malocclusion.
Adeno-tonsillar hypertrophy is the most common cause of obstructive sleep apnea syndrome (OSAS) in childhood and may also play a role in the development of craniofacial abnormalities. The mode of breathing and the morphology of the dental arch are very closely connected. Most of the children who came to the ENT clinic had malocclusions. The early performance of surgical treatment on hypertrophied tonsils and/or adenoids influenced greatly the state of health and morphology of the dental arch. In the process of diagnosis and treatment of children with OSAS it is necessary to have multidisciplinary cooperation, especially between the otolaryngologist and the orthodontist.


One-step immunoassay for measuring protein concentrations in plasma, based on precipitate-enhanced ellipsometry.
Standard enzyme immunoassays (EIAs) require washing steps to remove excess enzyme-antibody complexes. Such washing is laborious, lengthens assay time, and increases assay scatter. Recently, so-called precipitate-enhanced immunoassays (PEIAs) were introduced. Instead of color formation due to enzymatic conversion of a chromogenic substrate, this technique measures the rate of precipitate formation due to conversion of a substrate with a precipitating product. Such precipitation can be measured in the presence of active enzyme-antibody complexes in the buffer and no washing is required. In the present study this technique was used in a one-step PEIA, without washing steps, for the measurement of plasma concentrations of fatty-acid-binding protein. Horseradish peroxidase was used as tagging enzyme and diaminobenzidine as precipitating substrate. Precipitate formation was measured by ellipsometry. Assay time of the one-step PEIA was much shorter than that for an existing standard EIA. Test results can be obtained within minutes, depending on the sensitivity required. Assay precision of the one-step PEIA was better than that of the standard EIA. In the one-step assay, loss of surface-bound conjugate due to washing is prevented, which could explain part of the improved sensitivity compared to that of the two-step PEIA. More importantly, the presence of substrate-converting enzyme-antibody complexes in the buffer caused a large enhancement of precipitation.


Laparoscopic pancreaticoduodenectomy is effective in a porcine model.
Laparoscopic pancreatic surgery is rapidly evolving due to improving instrumentation and surgical techniques. The challenges confronting laparoscopic pancreaticoduodenectomy (LPD), however, are its technical difficulty and its appropriateness for oncologic treatment. This study sought to develop a novel technique for LPD in an acute porcine model and to evaluate the safety and feasibility of LPD before clinical trials are undertaken. The LPD procedure was performed in 10 pigs. Modified Child's reconstruction was performed intracorporeally. After the animals were killed, anastomotic sites were investigated by laparotomy. All the animals underwent LPD. The median operation time was 5 h, with minimal blood loss. One choledochojejunostomy had a small leak. The study proved LPD to be technically safe and feasible in an acute porcine model. Further studies and technical advances are necessary for transition of this clinical application of LPD to humans.


Computed tomography imaging of a leopard tortoise (Geochelone pardalis pardalis) with confirmed pulmonary fibrosis: a case report.
An approximately 20-year-old, female Leopard tortoise (Geochelone pardalis pardalis) was presented with dypsnea, wheezing, anorexia and depression. Whole body radiographs revealed generalized diffuse unstructured 'interstitial lung pattern' with thickened pulmonary septae while computed tomography (CT) showed emphysematous lung parenchyma and thickened pulmonary septae bordered by irregular ground-glass opacity with smaller areas of 'honeycombing'. These imaging findings together with histopathologic findings were compatible with chronic, extensive 'interstitial' pulmonary fibrosis.


The fetal-maternal interface of the nine-banded armadillo: endothelial cells of maternal sinus are partially replaced by trophoblast.
The evolution of invasive placentation in the stem lineage of eutherian mammals entailed resolution of the incompatibility between a semi-allogenic fetus and the maternal immune system. The haemochorial placenta of nine-banded armadillo (Dasypus novemcinctus) is thought to conceal itself from the maternal immune system to some degree by developing inside a preformed blood sinus, with minimal contact with the uterine connective tissue. In the present study, we elucidate the micro-anatomical relationship between fetal and maternal tissue of the nine-banded armadillo using histochemical and immunohistochemical tools. We conclude that the chorio-allantoic villi are separated from the myometrium by a vascular endothelial layer, as previously proposed. However, we also observe that the trophoblast cells establish direct contact with the endometrial stroma on the luminal side of the endometrium by partially replacing the endothelial lining of the sinus. Further, we demonstrate the presence of leukocytes, perhaps entrapped, in the placental fibrinoids at the interface between the intervillous space and the endometrial arcade. The trophoblast of the armadillo invades the uterine tissue to a greater extent than was previously believed. We discuss the implications of this finding for the fetal-maternal immune tolerance.


Management of distal humerus fractures with minifragment fixation.
Minifragment implants provide several advantages for the stabilization of distal humerus fractures. Compared with small fragment implants, minifragment implants may provide enhanced fracture fixation because a greater number of screws can be placed into the distal fragments. In addition, minifragment plates are easier to contour and less prominent. We describe the surgical technique of minifragment fixation.


International application of a new probability algorithm for the diagnosis of coronary artery disease.
A new discriminant function model for estimating probabilities of angiographic coronary disease was tested for reliability and clinical utility in 3 patient test groups. This model, derived from the clinical and noninvasive test results of 303 patients undergoing angiography at the Cleveland Clinic in Cleveland, Ohio, was applied to a group of 425 patients undergoing angiography at the Hungarian Institute of Cardiology in Budapest, Hungary (disease prevalence 38%); 200 patients undergoing angiography at the Veterans Administration Medical Center in Long Beach, California (disease prevalence 75%); and 143 such patients from the University Hospitals in Zurich and Basel, Switzerland (disease prevalence 84%). The probabilities that resulted from the application of the Cleveland algorithm were compared with those derived by applying a Bayesian algorithm derived from published medical studies called CADENZA to the same 3 patient test groups. Both algorithms overpredicted the probability of disease at the Hungarian and American centers. Overprediction was more pronounced with the use of CADENZA (average overestimation 16 vs 10% and 11 vs 5%, p less than 0.001). In the Swiss group, the discriminant function underestimated (by 7%) and CADENZA slightly overestimated (by 2%) disease probability. Clinical utility, assessed as the percentage of patients correctly classified, was modestly superior for the new discriminant function as compared with CADENZA in the Hungarian group and similar in the American and Swiss groups. It was concluded that coronary disease probabilities derived from discriminant functions are reliable and clinically useful when applied to patients with chest pain syndromes and intermediate disease prevalence.


Knowledge and Attitude of Patients, and Practice of the Arrest of Breast Cancer in Outpatient Consultations in Mastology at the General Hospital of Huambo, Angola.
This work aims to understand the knowledge and perceptions of women aged over 40 years with breast cancer seen in mastology outpatients at the Maternity Hospital of Huambo, central Angola, from February to August 2010. It also examines the clinical practice of prevention and detection of breast cancer. The research consisted of a collection of descriptive, cross-sectional data through a questionnaire. Statistical analysis of the data was performed using Epi Info, version 6.04b. In our sample, half of the women were single, all had history of breast cancer in the family, and most had heard of breast self-examination, with the primary source of information being the mass media. Almost all women reported that it was important to perform self-examination and that they were aware of the seriousness of breast cancer, and although most of them had not been taught how to do breast self-examination, almost all knew the basics of how to do it. Some 17.6% had heard of mammography, but none had ever had a mammogram.


Non-linguistic effects of language switching training.
What is the relationship between bilingual language control (BLC) mechanisms and domain-general executive control (EC) processes? Do these two domains share some of their mechanisms? Here, we take a novel approach to this question, investigating whether short-term language switching training improves non-linguistic task switching performance. Two groups of bilinguals were assigned to two different protocols; one group was trained in language switching (switching-task training group) another group was trained in blocked language picture naming (single-block training group). Both groups performed a non-linguistic and linguistic switching task before (pre-training) and after training (post-training). Non-linguistic and linguistic switch costs decreased to a greater extent for the switching-task training than for the single-block training group from pre- to post-training. In contrast, mixing costs showed similar reductions for both groups. This suggests short-term language switching training can transfer to the non-linguistic domain for certain sub-mechanisms (i.e., switch cost). Thus, there is some overlap of the control mechanisms across domains.


Method 300: a complementary teaching methodology in Dentistry.
This study evaluated Method 300, a complementary teaching methodology in Dentistry. Thirty participants were divided into 6 groups according to the scores obtained in a placement test ranging from 0 to 10. Students with scores lower than 6 were classified as having poor academic performance; students with scores equal to or greater than 6 were considered as having good academic performance. Each group included at least one student with good performance. Our methodology consisted of two application cycles, each including one different test; however, only students with low performance could undergo the second testing. Students held meetings twice a week for one hour and thirty minutes. Of the 54 students initially enrolled in the subject, 24 dropped out, leaving 30 students who completed all the proposed activities. In cycle 1, 24 (80%) students showed poor academic performance and 6 (20%) good. Students with poor performance in P1 significantly improved after P1 300 test application (P < 0.001). After cycle 1 activities, all 30 participants showed significant improvement. In cycle 2, the number of students with good performance tripled when compared to cycle 1, resulting in a decrease in the number of students with poor performance (P = 0.205). Results show that the Method 300 is an important teaching-learning resource in Dentistry, to be used as a complementary methodology to lectures.


A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO.
Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO) and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility. We expanded the existing framework for PANCPRO and BRCAPRO to jointly model risk of pancreatic, breast, and ovarian cancer and validated this new model, BRCAPANCPRO on three data sets each reflecting the common target populations. BRCAPANCPRO outperformed the prior BRCAPRO and PANCPRO models and yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUCs 0.79, 95% CI: 0.73-0.84 and 0.70, 95% CI: 0.60-0.80) in families seen in high-risk clinics and pancreatic cancer family registries, respectively. In addition, BRCAPANCPRO was reasonably well calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.81 [0.69, 0.94]). The BRCAPANCPRO model provides improved risk assessment over our previous risk models, particularly for pedigrees with a co-occurrence of pancreatic cancer and breast and/or ovarian cancer.


Characterization and algicidal activity of bacteria from the phycosphere of the harmful alga Karenia mikimotoi.
Harmful algal blooms (HABs) are detrimental to aquatic ecosystems; thus, economical and practical HAB control methods are needed. We analyzed a microbial community closely related to the alga Karenia mikimotoi, which has HABs that can be toxic to aquatic environments. We studied the relationship between algicidal bacteria and the microbial community of K. mikimotoi culture using culture-dependent and culture-independent methods. Bacterial strains Marinobacter sp. (O-7) and Pseudomonas sp. (D-2) were isolated from a K. mikimotoi seawater culture containing a mixed microbial community and determined to have algicidal activity. Both strains produced alga-lysing substances that were toxic to K. mikimotoi. The algicidal extracellular substances produced by D-2 were stable at temperatures ranging from - 80 to 120 °C but sensitive to strong acidic/alkaline conditions. The substances produced by O-7 were inactivated at high temperatures and strong alkaline conditions. Extracellular substances produced by O-7 and D-2 caused K. mikimotoi and Prorocentrum donghaiense cell lysis, but no changes or inhibitory effects occurred in two other chlorophyta groups. O-7 and D-2 exhibited significantly greater algicidal activity during the logarithmic growth phase of K. mikimotoi growth compared to the stationary phase. Culture-independent analysis of the microbial community in association with K. mikimotoi was made using Illumina MiSeq sequencing. Phylogenetic analysis showed that Proteobacteria was the dominant bacterial population in the phycosphere of K. mikimotoi, containing Marinobacter sp. and Pseudomonas sp.. The Marinobacter was abundant and accounted for 5.3% of the total. Our results indicate that certain bacterial species from K. mikimotoi culture might be effective for removal of HABs.


Novel applications of monoclonal antibodies.
The ability to "engineer" antibodies, using the techniques of somatic cell genetics and cell fusion, has opened a new era in immunochemistry. No longer are immunologists, limited by the vagaries of polyclonal antibody production. Using hybridoma technology, consistent preparations of precisely defined monoclonal antibodies are now available. Immunochemists are free to pick and choose those precisely defined characteristics of a homogeneous species of antibody that are best suited for a given application. To date, monoclonal antibodies have been used primarily as research chemicals. However, the implications of this new technology for diagnostic, therapeutic, and separation systems are rapidly becoming apparent.


Atypical "Sclerosing" Osteoblastic Neoplasm: A Tumor of Intermediate Biological Potential Between Usual Osteoblastoma and Conventional Osteosarcoma.
The existence of "aggressive" osteoblastoma (OB) or malignant transformation of OB is controversial. Over a few decades, we have encountered a group of "borderline" sclerosing osteoblastic lesions that are difficult to classify, tending toward local recurrence, especially following curettage. A search of the consultative and institutional files from 3 co-authors for atypical OB, malignant transformation of OB, well-differentiated osteosarcoma (OS), and OB-like OS diagnoses revealed 8 similar cases. There were 6 males and 2 females, ages 11 to 55 years (mean, 26 y). Three arose in metatarsals, 2 in the fibula, and 1 each in the humerus, tibia, and femur. Radiologically, most were expansile, lytic to sclerotic, with circumscribed and at least partially sclerotic borders. Pathologically, all displayed a predominant, sclerosing sheet-like neoplastic bone growth pattern, associated with minor components of conventional OB. No solid sheets of osteoblasts or permeation of surrounding bone were identified. Six cases were reviewed by >1 expert orthopedic pathologist, often with divergent opinions. Four were initially diagnosed as OB, 2 as low-grade OS, 1 as high-grade OS, and 1 as atypical sclerosing osteoblastic neoplasm. Clinical follow-up for 7 patients ranged from 12 to 138 months (mean, 71 mo). Four underwent curettage only; 2, curettage and en bloc resection with negative margins; 1, en bloc intralesional resection, and 1 amputation. 5 locally recurred, with 3 "reclassified" as OSs. One local recurrence was considered dedifferentiation. Whether these tumors represent low-grade OSs or aggressive forms of OB remains unclear. We recommend classifying these neoplasms as "atypical sclerosing osteoblastic neoplasm" and performing complete resection with negative margins.


Virome of crab-eating (Cerdocyon thous) and pampas foxes (Lycalopex gymnocercus) from southern Brazil and Uruguay.
Crab-eating (Cerdocyon thous) and Pampas foxes (Lycalopex gymnocercus) are wild canids distributed in South America. Domestic dogs (Canis lupus familiaris) and wild canids may share viral pathogens, including rabies virus (RABV), canine distemper virus (CDV), and canine parvovirus 2 (CPV-2). To characterize the virome of these wild canid species, the present work evaluated the spleen and mesenteric lymph node virome of 17 crab-eating and five Pampas foxes using high-throughput sequencing (HTS). Organ samples were pooled and sequenced using an Illumina MiSeq platform. Additional PCR analyses were performed to identify the frequencies and host origin for each virus detected by HTS. Sequences more closely related to the Paramyxoviridae, Parvoviridae and Anelloviridae families were detected, as well as circular Rep-encoding single-stranded (CRESS) DNA viruses. CDV was found only in crab-eating foxes, whereas CPV-2 was found in both canid species; both viruses were closely related to sequences reported in domestic dogs from southern Brazil. Moreover, the present work reported the detection of canine bocavirus (CBoV) strains that were genetically divergent from CBoV-1 and 2 lineages. Finally, we also characterized CRESS DNA viruses and anelloviruses with marked diversity. The results of this study contribute to the body of knowledge regarding wild canid viruses that can potentially be shared with domestic canids or other species.


Aerobic decolorization and degradation of azo dyes by growing cells of a newly isolated yeast Candida tropicalis TL-F1.
The aim of this work was to investigate the decolorization and degradation of azo dyes by growing cells of a new yeast strain TL-F1 which was isolated from the sea mud. Strain TL-F1 was identified as Candida tropicalis on the basis of 28S rDNA analysis. Various azo dyes (20mg/L) were efficiently decolorized through aerobic degradation. Meantime, the effects of different parameters on both decolorization of Acid Brilliant Scarlet GR and growth of strain TL-F1 were investigated. Furthermore, possible degradation pathway of the dye GR was proposed through analysis of metabolic products using UV-Vis spectroscopy and HPLC-MS methods. As far as it is known, it is the first systematic research on a C. tropicalis strain which is capable of efficiently decolorizing various azo dyes under aerobic condition. This work provides a potentially useful microbial strain TL-F1 for treatment of azo dye contaminated wastewater.


Design considerations for array CGH to oligonucleotide arrays.
Representational oligonucleotide microarray analysis has been developed for detection of single nucleotide polymorphisms and/or for genome copy number changes. In this process, the intensity of hybridization to oligonucleotides arrays is increased by hybridizing a polymerase chain reaction (PCR)-amplified representation of reduced genomic complexity. However, hybridization to some oligonucleotides is not sufficiently high to allow precise analysis of that portion of the genome. In an effort to identify aspects of oligonucleotide hybridization affecting signal intensity, we explored the importance of the PCR product strand to which each oligonucleotide is homologous and the sequence of the array oligonucleotides. We accomplished this by hybridizing multiple PCR-amplified products to oligonucleotide arrays carrying two sense and two antisense 50-mer oligonucleotides for each PCR amplicon. In some cases, hybridization intensity depended more strongly on the PCR amplicon strand (i.e., sense vs. antisense) than on the detection oligonucleotide sequence. In other cases, the oligonucleotide sequence seemed to dominate. Oligonucleotide arrays for analysis of DNA copy number or for single nucleotide polymorphism content should be designed to carry probes to sense and antisense strands of each PCR amplicon to ensure sufficient hybridization and signal intensity.


Blanking period antiarrhythmic drugs after catheter ablation for atrial fibrillation: a meta-analysis of randomized controlled trials.
Antiarrhythmic drugs (AADs) are frequently prescribed following catheter ablation (CA) for atrial fibrillation (AF). However, to date, there is a lack of large-scale, multicenter controlled studies that have confirmed the efficacy of AADs in reducing the incidence of late recurrence of AF after CA. Furthermore, the optimal duration of short-term use of AADs after CA remains a controversial topic. PubMed, Embase, Cochrane Library, CNKI, and ClinicalTrials.gov were searched until April 25, 2022. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of blanking period AADs in predicting both early and late recurrence of AF. In addition, Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the quality of evidence in this meta-analysis. 12 RCTs with 3,625 patients were included in this meta-analysis. Short-term use of AADs after AF ablation reduced the risk of early recurrence of AF compared with the no-AADs group. In the subgroup analysis of AADs use time, it was found that only using AADs for more than 2 months can reduce the early recurrence of AF after CA. However, when compared with the no-AADs group, short-term use of AADs after CA did not reduce the incidence of late recurrence of AF. Short-term use of AADs (more than 2 months) can reduce the early recurrence but not the late recurrence of AF after CA.


One-pot hard template synthesis of mesoporous spinel nanoparticles as efficient catalysts for low temperature CO oxidation.
Co-Fe, Cu-Cr, and Co-Mn mixed oxide catalysts were prepared using a one-pot hard template synthesis method, and their catalytic performance was investigated before and after the rearrangement of the template. To evaluate the structural properties of the catalysts, various analyses were employed, including the BET, XRD, H2-TPR, FE-SEM, EDX, and X-ray digital mapping of the elements. The results indicated that the rearrangement of the catalyst structure had a profound effect on the structural and catalytic properties, so that in all three synthesized catalysts, the specific surface and the reducibility increased significantly, and the crystalline structure and morphology of the catalysts changed remarkably. The specific surface area of the CoFe, CuCr, and CoMn catalysts increased from 3.5, 1.1, and 72.9 m2/g to 151.3, 52.8, and 108.0 m2/g, respectively. These structural changes significantly increased the catalytic performance. The results indicated that the 100% conversion temperature of the CoMn catalyst as the optimal sample after rearrangement was reduced from 250 to 125 °C. Also, the stability of the CoMn catalyst in dry and wet conditions was investigated and the results indicated that the presence of water vapor reduced the activity and stability of the catalyst. The activation energy was also calculated on Co-Mn catalyst (59.5 kJ/mol) and the results confirmed that the most probable mechanism for this reaction was the MVK mechanism.


A moderated-mediation analysis of pathways in the association between Veterans' health and their spouse's relationship satisfaction: The importance of social support.
Military personnel and Veterans are at increased risk of mental and physical health conditions, which can impact their families. Spouses often perform a vital role in caring for service members and Veterans facing illness or injury, which can lead to caregiver burden. In turn, this may contribute to relationship issues. Research suggests that ensuring that spouses are well supported can alleviate some of these negative effects. The current study examined whether social support received by spouses of newly released Veterans buffers the impact of Veterans' health on caregiver burden, subsequently impacting spouses' relationship satisfaction. Data were collected as part of the Canadian Armed Forces Transition and Well-being Survey. The sample included N = 595 spouses of Regular Force Veterans who released in 2016 with at least 2 years of service. We examined Veterans' mental and physical health and spouses' caregiver burden, social support, and relationship satisfaction. A moderated mediation model was tested using structural equation modeling. There was a significant indirect association between Veterans' health (both physical and mental) and spouses' relationship satisfaction through caregiver burden. Furthermore, social support moderated the association, as evidenced by a weaker association between Veterans' health and caregiver burden at low levels (-1SD) of social support compared to high levels (+1SD). Findings suggest additional efforts should be made to ensure sufficient support is provided to spouses, especially when they are caring for a service member or Veteran facing illness or injury, to strengthen their families' well-being.


Id proteins in cell cycle control and cellular senescence.
The Id family of helix-loop-helix (HLH) proteins are thought to affect the balance between cell growth and differentiation by negatively regulating the function of basic-helix-loop-helix (bHLH) transcription factors. Although it has been suggested for some time that Id is involved in cell cycle regulation, little is known about the molecular mechanism of this control. Recent studies, however, have revealed that Id binds to important cell cycle regulatory proteins other than bHLH proteins. Two such proteins, pRB (retinoblastoma tumour suppressor protein) family proteins and Ets-family transcription factors are known to play key roles in cell cycle regulation, transformation and tumour suppression. Through the characterization of these pathways we will begin to understand the mechanisms by which Id controls normal and abnormal cell cycle progression.


Impacts of local circulations on the wintertime air pollution in the Guanzhong Basin, China.
Urbanization and industrialization in the recent 30years have caused frequent heavy haze pollution in the Guanzhong basin, China during wintertime. Based on the categorized large-scale synoptic situations, the local circulation and its impact on the air pollution in the basin have been investigated using observational data analyses and model simulations with the WRF-CHEM model. The simulated mountain-valley breeze circulations are well established under most of the large-scale synoptic situations in the south-north direction. The downward mountain-breeze not only causes the convergence zone in the basin but also tends to bring the pollutants back from the mountain areas to the basin and enhance pollutants concentrations in the evening. The intensity of the mountain-valley breeze circulations may be different under different synoptic situations, but in general, aside emissions, every pollution event is the synthetic result of the synoptic situation at the large scale and the local circulation at the small scale in the Guanzhong basin.


The effect of zinc on the dithiocarbamate-induced mobilization of cadmium deposits in mice.
In comparison with similar experiments in which no zinc acetate was used, the addition of small amounts of zinc acetate to sodium N-methyl-N-dithiocarboxyglucamine produces a significant increase in the amount of cadmium mobilized from the liver and kidneys of mice loaded ip with 10 mg CdCl2.2.5H2O/kg 2 wk prior to the initiation of treatment. Neither treatment results in the transport of significant amounts of cadmium to the brain. The injection of zinc acetate alone did not produce this effect. Experiments in which zinc acetate in drinking water was administered to cadmium-loaded animals showed that the liver and kidney cadmium levels were significantly increased, presumably via zinc-mediated processes in which cadmium from other organs was mobilized to the liver and kidneys.


Effect of cysteine modifications on the activity of the 'small' Clostridium perfringens sialidase.
The 'small' (43 kDa) sialidase of Clostridium perfringens is inhibited by low concentrations of mercury ions. For the investigation of possible functional roles of the enzyme's four cysteine residues at the amino acid positions 2, 282, 333 and 349, they were separately altered to serine by site-directed mutagenesis. The four mutant sialidases expressed in E. coli and purified by metal chelate chromatography were markedly reduced in specific activity when compared to the wild-type enzyme but with the exception of C282S exhibited similar K(M)-values indicating an unchanged mode of substrate binding. The substrate specificity was also conserved for C2S, C282S, and C333S. Only the C349S sialidase exhibited a higher relative activity with colominic acid and the alpha2,6-linked sialic acid of sialyllactose compared to the alpha2,3-linked isomer than the other mutants. Chemical modifications with the thiol-blocking reagents N-ethylmaleimide (NEM), p-chloromercuribenzoate (pCMB) and HgCl2 had little effect on the C282S sialidase, e.g., 6% inhibition by 5 mM NEM compared to reductions in activity between 65 and 90% for the wild-type and other mutant enzymes, supporting the idea that among the enzyme's cysteines, Cys-282 has the highest structural or functional significance. The results also explain the higher mercury tolerance of Salmonella typhimurium and Clostridium tertium sialidases, which have the positions equivalent to Cys-282 altered to Val and Thr, respectively, indicating that the thiol group of Cys-282, despite being situated near the active site, is not involved in catalysis.


Multivariate optimization of an analytical method for the analysis of dog and cat foods by ICP OES.
Experimental design methodology was used to optimize an analytical method for determination of the mineral element composition (Al, Ca, Cd, Cr, Cu, Ba, Fe, K, Mg, Mn, P, S, Sr and Zn) of dog and cat foods. Two-level full factorial design was applied to define the optimal proportions of the reagents used for microwave-assisted sample digestion (2.0 mol L(-1) HNO3 and 6% m/v H2O2). A three-level factorial design for two variables was used to optimize the operational conditions of the inductively coupled plasma optical emission spectrometer, employed for analysis of the extracts. A radiofrequency power of 1.2 kW and a nebulizer argon flow of 1.0 L min(-1) were selected. The limits of quantification (LOQ) were between 0.03 μg g(-1) (Cr, 267.716 nm) and 87 μg g(-1) (Ca, 373.690 nm). The trueness of the optimized method was evaluated by analysis of five certified reference materials (CRMs): wheat flour (NIST 1567a), bovine liver (NIST 1577), peach leaves (NIST 1547), oyster tissue (NIST 1566b), and fish protein (DORM-3). The recovery values obtained for the CRMs were between 80 ± 4% (Cr) and 117 ± 5% (Cd), with relative standard deviations (RSDs) better than 5%, demonstrating that the proposed method offered good trueness and precision. Ten samples of pet food (five each of cat and dog food) were acquired at supermarkets in Aracaju city (Sergipe State, Brazil). Concentrations in the dog food ranged between 7.1 mg kg(-1) (Ba) and 2.7 g kg(-1) (Ca), while for cat food the values were between 3.7 mg kg(-1) (Ba) and 3.0 g kg(-1) (Ca). The concentrations of Ca, K, Mg, P, Cu, Fe, Mn, and Zn in the food were compared with the guidelines of the United States' Association of American Feed Control Officials (AAFCO) and the Brazilian Ministry of Agriculture, Livestock, and Food Supply (Ministério da Agricultura, Pecuária e Abastecimento-MAPA).


Metabolism of N-nitrosomorpholine by the rat in vivo and by rat liver microsomes and its oxidation by the Fenton system.
N-Nitrosomorpholine is converted into N-nitroso-2-hydroxymorpholine by rat liver microsomes and by the Fenton oxidation system. The hydroxy derivative was also synthesised by the oxidation of N-nitrosodiethanolamine with permanganate and characterized as the methoxime and the 2,4-dinitrophenylhydrazone. The Fenton system also afforded products believed to be N-nitroso-2-morpholone, and the 2-hydroperoxy- and 2-peroxy-derivatives of N-nitrosomorpholine. The only urinary metabolite definitely identified was N-nitrosodiethanolamine. The significance of metabolic 2-hydroxylation in relation to the carcinogenic action of N-nitrosomorpholine is discussed.


Degradation products of streptozotocin do not induce hyperglycemia in rats.
The present study was conducted to determine whether degradation products of streptozotocin formed under various conditions induce hyperglycemia in rats. Streptozotocin is completely degraded in pH 7.4 buffer in 4 hr and even more rapidly in plasma. Streptozotocin degradation products resulting from incubation in pH 7.4 phosphate buffer or in plasma were not diabetogenic in rats.


The monoculture of cord-blood-derived CD34+ cells by an automated, membrane-based dynamic perfusion system with a novel cytokine cocktail.
Human leukocyte antigen (HLA)-matched cord blood (CB) transplantation is a procedure for the treatment of certain hematological malignancies, hemoglobinopathies, and autoimmune disorders. However, one of the challenges is to provide a sufficient number of T cell-depleted hematopoietic stem and progenitor cells. Currently, only 4%-5% of the CB units stored in CB banks contain enough CD34+ cells for engrafting 70-kg patients. To support this clinical need, we have developed an automated expansion protocol for CB-derived CD34+ cells in the Quantum system's dynamic perfusion bioreactor using a novel cytokine cocktail comprised of stem cell factor (SCF), thrombopoietin (TPO), fms-like tyrosine kinase 3 ligand (Flt-3L), interleukin-3 (IL-3), IL-6, glial cell line-derived neurotrophic factor (GDNF), StemRegenin 1 (SR-1), and a fibronectin-stromal-cell-derived factor-1 (SDF-1)-coated membrane. In an 8-day expansion of a 2 × 106 positively selected CD34+ cell inoculum from 3 donor lineages, the mean cell harvest and cell viability were 1.02 × 108 cells and 95.5%, respectively, and the mean frequency of the CD45+CD34+ immunophenotype was 54.3%. The mean differentiated cell frequencies were 0.5% for lymphocytes, 15.8% for neutrophils, and 15.4% for platelets. These results demonstrate that the automated monoculture protocol can support the expansion of CD34+ cells with minimal lymphocyte residual.


Are habitually barefoot children compelled to wear ill-fitting school shoes? A cross-sectional study.
Research shows that ill-fitting shoes can negatively impact the development of the pediatric foot, in a very direct manner. The primary aim of the study was to determine if the dimensions of available prescribed school shoes fit the foot dimensions of habitually barefoot South African children and adolescents. A cross-sectional observational study was conducted where static standing foot measurements of children and adolescents from urban and rural schools were obtained with a mobile caliper. The maximum heel-toe-length and foot width with an added 10 mm toe- and width fit allowance to each participant, were compared to the corresponding school shoe length and shoe width available in retail. A mixed model ANOVA was used to compare foot dimensions between gender, age and side. Six hundred and ninety-eight school children (N = 698) (431 girls; 267 boys; average age 10.86 years, SD = 2.55) were participants. A total of seventy-seven (N = 77) black coloured prescribed school shoes currently available in retail ranging from different styles and brands were measured. Results show that, comparing the shoe length and maximum heel-toe-length of participants, as well as taking 10 mm toe allowance into account, fifty-nine percent (59%) of children wore shoes that were not the correct length. With regards to the shoe width and the added 10 mm of width fit allowance, ninety-eight percent (98%) of the shoes worn by participants were too narrow for their feet. Results confirmed that school shoes currently available in retail, are not suited for the habitually barefoot population studied. It is recommended that the shoe manufacturing industry should consider the shoe width of school shoes for children and adolescents in habitually barefoot populations to avoid the long-term negative effect of ill-fitting shoes on the pediatric foot.


ALOBAR HOLOPROSENCEPHALY, CLEFT LIP/PALATE, URORECTAL SEPTUM MALFORMATION SEQUENCE AND CONGENITAL PERINEAL HERNIA IN A FETUS.
We report on a fetus with alobar holoprosencephaly, complete cleft lip and palate, urorectal septum malformation sequence and perineal hernia. To our knowledge this appears to be a novel fetal malformation syndrome.


Behavioral Strategies in Diagnostic Stewardship.
Diagnostic stewardship refers to the responsible and judicious use of diagnostic tests to reduce low value care and improve patient outcomes. This article provides an overview of behavioral strategies, their relevance to diagnostic stewardship and highlights behavioral determinants that drive diagnostic testing behavior, drawing on theoretic frameworks. Additionally, we provide concrete examples of evidence-based behavioral strategies for promoting appropriate diagnostic testing while acknowledging associated challenges. Finally, we highlight the significance of evaluating these strategies and provide an overview of evaluation frameworks and methods.


An Economic Analysis of Transjugular Intrahepatic Portosystemic Covered Stent Shunt for Variceal Bleeding and Refractory Ascites in a Spanish Setting.
The primary aim is to estimate the cost-effectiveness of transjugular intrahepatic portosystemic stent shunt (TIPSS) in two indications from a Spanish perspective. Firstly, as pre-emptive treatment for patients with acute variceal bleeding (indication 1) compared with endoscopic band ligation plus drug therapy. Secondly, to treat refractory ascites (indication 2) compared with large volume paracentesis. A two-state (alive and dead) Markov model was developed to capture the costs and health impact for the two indications over a 2-year time horizon with monthly cycles. In the alive state, patients could experience adverse event(s), associated with costs and disutility, such as recurrent variceal bleeding, ascites, and hepatic encephalopathy. Discount rates of 3% for utilities and costs and a cost-effectiveness threshold of €25,000 per QALY were applied. In the base case analysis, TIPSS was estimated to be cost-effective as a pre-emptive treatment for indication 1 (incremental cost and QALYs of - €230 and 0.211, respectively). TIPSS also remained cost-effective (€16,819/QALY) in a conservative scenario analysis, conducted with an alternate source for clinical parameters. The key drivers of the outcomes were survival for the comparator arm, mean band ligation outpatient procedures, and TIPSS treatment costs. TIPSS was estimated to dominate the comparator for indication 2 (incremental cost and QALYs of - €25,687 and 0.531, respectively). The key drivers of the outcomes were monthly paracentesis sessions and cost per inpatient stay for those undergoing paracentesis. TIPSS is likely to be a cost-effective and a cost-saving treatment in patients with cirrhosis in indications 1 and 2, compared with standard treatments. The analyses estimate clinical benefits along with reduced healthcare costs from avoided downstream resource consumption.


The crystal structure of the dimeric colicin M immunity protein displays a 3D domain swap.
Bacteriocins are proteins secreted by many bacterial cells to kill related bacteria of the same niche. To avoid their own suicide through reuptake of secreted bacteriocins, these bacteria protect themselves by co-expression of immunity proteins in the compartment of colicin destination. In Escherichia coli the colicin M (Cma) is inactivated by the interaction with the Cma immunity protein (Cmi). We have crystallized and solved the structure of Cmi at a resolution of 1.95Å by the recently developed ab initio phasing program ARCIMBOLDO. The monomeric structure of the mature 10kDa protein comprises a long N-terminal α-helix and a four-stranded C-terminal β-sheet. Dimerization of this fold is mediated by an extended interface of hydrogen bond interactions between the α-helix and the four-stranded β-sheet of the symmetry related molecule. Two intermolecular disulfide bridges covalently connect this dimer to further lock this complex. The Cmi protein resembles an example of a 3D domain swapping being stalled through physical linkage. The dimer is a highly charged complex with a significant surplus of negative charges presumably responsible for interactions with Cma. Dimerization of Cmi was also demonstrated to occur in vivo. Although the Cmi-Cma complex is unique among bacteria, the general fold of Cmi is representative for a class of YebF-like proteins which are known to be secreted into the external medium by some Gram-negative bacteria.


SENP3-mediated deSUMOylation of c-Jun facilitates microglia-induced neuroinflammation after cerebral ischemia and reperfusion injury.
Recent evidences have implicated that SENP3 is a deSUMOylase which possesses neuronal damage effects in cerebral ischemia. However, its role in microglia remains poorly understood. Here, we found that SENP3 was upregulated in the peri-infarct areas of mice following ischemic stroke. Furthermore, knockdown of SENP3 significantly inhibits the expression of proinflammatory cytokines and chemokines in microglial cells. Mechanistically, SENP3 can bind and then mediated the deSUMOylation of c-Jun, which activated its transcriptional activity, ultimately followed by the activation of MAPK/AP-1 signaling pathway. In addition, microglia-specific SENP3 knockdown alleviated ischemia-induced neuronal damage, and markedly diminished infract volume, ameliorated sensorimotor and cognitive function in animals subjected to ischemic stroke. These results indicated SENP3 functions as a novel regulator of microglia-induced neuroinflammation by activating the MAPK/AP-1 signaling pathway via mediating the deSUMOylation of c-Jun. Interventions of SENP3 expression or its interaction with c-Jun would be a new and promising therapeutic strategy for ischemic stroke.