Association of obesity, visceral adiposity, and sarcopenia with an increased risk of metabolic syndrome: A retrospective study.
Metabolic syndrome (MS) is a global health problem associated with an increased risk of diabetes mellitus (DM), cardiovascular disease (CVD), and cancer. Body composition parameters, including obesity, visceral adiposity, and sarcopenia contribute to the development of MS and CVD. Previous studies have investigated the association of individual body composition parameters with MS. Studies analyzing the association between multiple body composition parameters and MS have been rare. We aimed to investigate the association between MS and multiple body composition parameters, including obesity, visceral adiposity, and sarcopenia. A total of 13,620 subjects who underwent voluntary routine checkups at the Health Care Center of our institution between October 2014 and December 2019 were enrolled. Only data from the first examination of subjects who underwent repeated checkups were included. Clinical and laboratory data were collected. Skeletal muscle mass and visceral fat area (VFA) were measured using bioelectrical impedance analysis. Appendicular skeletal muscle mass (ASM) was divided by body weight (in kg) and expressed as a percentage (calculated as, ASM% = ASM × 100/Weight). Data were compared between the groups based on obesity, VFA, and ASM%. Logistic regression analysis was performed to determine the risk of MS in each group. Body mass index and VFA were significantly higher in subjects with MS than in those without MS. ASM% was significantly lower in subjects with MS than in those without MS. Subjects with obesity, visceral adiposity, or sarcopenia had a higher prevalence of MS than those without. As the number of metabolic components increased from 0 to 5, we identified a decreasing trend of ASM% and an increasing trend of VFA and BMI (P for trend < 0.001 for all). In the paired analyses, all the three body composition parameters showed additive effects in predicting MS. In the logistic regression analysis, the three parameters were associated with an increased risk of MS after adjustment for age, sex, hypertension, DM, dyslipidemia, smoking, alcohol intake, and C-reactive protein. Obesity, visceral adiposity, and sarcopenia showed additive effects on MS prediction. Subjects with obesity, visceral adiposity, or sarcopenia were significantly associated with the increased risk of MS after adjustment for multiple confounders. Increasing skeletal muscle and reducing visceral fat may be strategies for the prevention or treatment of MS.


Effects of albuterol enantiomers on ciliary beat frequency in ovine tracheal epithelial cells.
beta(2)-Adrenergic agonists stimulate ciliary beat frequency (CBF), an integral part of mucociliary clearance. To evaluate the differential effects of albuterol enantiomers and their racemic mixture on ciliary function, CBF and intracellular calcium were measured at room temperature from single ovine airway epithelial cells with use of digital videomicroscopy. Baseline CBF was 7.2 +/- 0.2 (SE) Hz (n = 80 measurements). R-albuterol (10 microM to 1 mM) stimulated CBF in a dose-dependent manner to maximally 24.4 +/- 5.4% above baseline. Racemic albuterol stimulated CBF to maximally 12.8 +/- 3.6% above baseline, a significantly lower increase compared with R-albuterol alone, despite identical R-enantiomer amounts in both groups. Simultaneous recordings of intracellular calcium concentration and CBF from single cells indicated that the CBF increase in response to R-albuterol was mediated through beta-receptors and stimulation of protein kinase A, in a calcium-dependent and -independent fashion. S-albuterol had a negligible effect on CBF and did not change intracellular calcium. Together, these results suggest that R-albuterol is more efficacious than racemic albuterol in stimulating CBF. Thus S-albuterol may interfere with the ability of R-albuterol to increase CBF.


Glutamine uptake contributes to central sensitization in the medullary dorsal horn.
Mustard oil application to tooth pulp produces central sensitization in rat medullary dorsal horn (MDH) nociceptive neurons, which has been implicated in persistent pain mechanisms. We found that superfusion onto MDH of methylaminoisobutyric acid, a competitive inhibitor of the neuronal system A transporter for presynaptic uptake of glutamine (a glutamate precursor released from astroglia), significantly depressed development of mustard oil-induced central sensitization in rat MDH nociceptive neurons. This finding indicates that the system A transporter is required for the expression of central sensitization and confirms the important roles of astroglia, glutamine and presynaptic modulation of glutamate release in the development of central sensitization.


The Link between Activities of Daily Living and Cortisol in Late-Life Depression.
Dysregulated cortisol in older individuals is associated with neurodegeneration and executive dysfunction, among other negative health outcomes. Executive functioning deficits are believed to underlie declines in functioning among older adults. Despite these associations, there is limited research examining the relationship between cortisol and impaired functional status. The present study examined the relationship between cortisol and functional status in a community sample of 51 older adults with depression. Pearson correlations and ordinal regressions were used to determine whether greater cortisol dysregulation was associated with ADL and IADL impairment. Results indicated that individuals who had higher levels of cortisol also tended to demonstrate greater functional deficits. These findings remained true when functional status was measured by either a clinician-rated tool or a self-report measure. The results of this study provide preliminary support for the hypothesis that elevated cortisol, in the context of depression, is associated with functional status deficits in older adults. Findings from this study begin to fill the gap in research examining the relationship between cortisol and functional impairment in older adults and suggest that unique information can be gathered with the use of different functional status measures.


Migration of mineral oil from party plates of recycled paperboard into foods: 1. Is recycled paperboard fit for the purpose? 2. Adequate testing procedure.
Party plates made of recycled paperboard with a polyolefin film on the food contact surface (more often polypropylene than polyethylene) were tested for migration of mineral oil into various foods applying reasonable worst case conditions. The worst case was identified as a slice of fried meat placed onto the plate while hot and allowed to cool for 1 h. As it caused the acceptable daily intake (ADI) specified by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) to be exceeded, it is concluded that recycled paperboard is generally acceptable for party plates only when separated from the food by a functional barrier. Migration data obtained with oil as simulant at 70°C was compared to the migration into foods. A contact time of 30 min was found to reasonably cover the worst case determined in food.


A quantitative electron microscopic analysis of the membrana granulosa of rat preovulatory follicles.
The ultrastructure of the membrana granulosa (MG) of rat preovulatory follicles was examined using stereological techniques. Organelles studied were nuclei, mitochondria, lipid droplets (LD), lysosomes, and smooth and rough endoplasmic reticulum (SER, RER). The peripheral region of the MG contained the greatest volume of mitochondria, LD and SER, organelles associated with steroidogenesis. The volume of RER, an organelle associated with protein production, was greatest in the cumulus oophorus. These results corroborate previous analyses and demonstrate that the rat MG is composed of discrete subregions.


Pulmonary langerhans cell histiocytosis: case series and literature review.
Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease with insidious onset and nonspecific manifestations. The objective of this article was to characterize the clinical manifestations and features of PLCH by retrospectively analyzing clinical data of patients with PLCH in addition to simultaneous review of literature.A retrospective analysis was conducted on clinical data of patients with PLCH (n = 7), whose conditions were diagnosed by biopsy from pulmonary tissue (n = 6) or enlarged lymph nodes in the neck (n = 1) and confirmed by PLCH typical radiological features on computed tomography (CT) scan, between January 2001 and September 2012 at the Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. The review of published reports was made to further emphasize the clinical manifestation and radiological features of PLCH.Long history of cigarette smoking was found in 6 patients. Two patients had recurrent pneumothorax and the other 2 had pulmonary arterial hypertension (World Health Organization group 5 pulmonary hypertension), diagnosed through ultrasonic cardiogram. The nodular shadows were revealed by chest CT scan in 5 patients, cystic shadows in 5 patients, and reticular shadows in 2 patients, as major manifestations, respectively; most of the lesions were located in the middle or upper segments of the lung. The obvious shrank of lesion was found in 1 patient after completely quitting smoking.The pathogenesis of PLCH might be closely associated with smoking. The cystic or nodular lesion was the typical radiological features. Further prospective studies with large sample size are required to further validate the study results and understand the clinical characteristics of PLCH to avoid misdiagnosis.


Epidemiology of gastrointestinal infections: lessons learned from syndromic testing, Region Zealand, Denmark.
The aim of this study was to investigate the value of syndromic diagnostic testing for a better understanding of the epidemiology of gastrointestinal infections in Denmark. Here we evaluated the QIAstat-Dx® Gastrointestinal (GI) Panel 1 assay on 18,610 fecal samples requested for analysis for enteric pathogens in Region Zealand, Denmark, in 1 year (October 1, 2021, to September 30, 2022). In total, 6905 (37%) samples were detected positive for one or more diarrhoeal bacteria, viruses, and protozoa. The most common bacterial, viral, and parasitic pathogens detected with the QIAstat-Dx® Gastrointestinal Panel 1 were EPEC (in patients ≥ 2 years of age) (n = 1420 (20.6%)), rotavirus (n = 948 (13.7%)), and Cryptosporidium spp. (n = 196 (2.84%)). We identified a large diversity in infections likely reflecting substantial differences in the epidemiology including origin of infections, mode of transmission, seasonality, age-dependent susceptibility to disease, severity, and travel history. All pathogens were detected as both single and coinfections. Viral infections peaked in March with a positive rate of 31.6%, and bacterial infections peaked in August with a positive rate of 35.3%. ETEC, Shigella/EIEC, EAEC, and P. shigelloides were most related to travel activity, and coinfections were frequent. The distribution of Ct values varied significantly between the pathogens, with the lowest Ct values (median 17-18) observed in astrovirus, adenovirus, and rotavirus. Our results highlight the value of providing extensive diagnostic testing on fecal samples for sufficient detection of relevant diarrhoeal pathogens for optimal clinical care.


Laboratory Evaluation of Optical Performance of Aspheric Monofocal Intraocular Lenses With Various Anti-misalignment Designs Under the Influence of Decentration and Tilt.
To assess the effectiveness and characteristics of aspheric monofocal intraocular lenses (IOLs) with different anti-misalignment designs. Three types of anti-misalignment IOLs (with aspheric balance curve design, ZO optic design, and high-order optical aspheric surface design) and no anti-misalignment IOLs were involved. From each type of these IOLs, +8.00, +17.00, and +26.00 diopter (D) lenses were used for detection at the 3- and 4.5-mm apertures. The modulation transfer function (MTF) and 50% of the maximum value of the MTF (MTF50) were measured while IOLs were centered, decentered by 0.3, 0.5, and 0.7 mm, and tilted by 3, 5, and 7 degrees. Within the average clinical range of IOL malpositions (0.3-mm decentration or 3.00-D tilt), the anti-misalignment design slightly reduced the negative effect of decentration and tilt (P = .1845 and .6495, t test) on the optical performance of IOLs. Beyond the average range, the anti-misalignment design narrowed the reductions of MTF50 from 23.18% to 8.60% for decentration and from 40.31% to 27.96% for tilt (P = .0010, two-factor analysis of variance). The optical performance varied in anti-misalignment IOLs with different diopters, types, and degrees of malpositions at different aperture sizes. In both photopic and mesopic conditions and all probable misalignments, from the perspective of MTF50, better sharpness generally may be achieved with the 8.00-D ZO optic designed lens and 17.00-D high-order optical aspheric surface designed lens. For 26.00-D IOLs with different misalignments, the ABC design was more resistant to decentrations, whereas the high-order optical aspheric surface design was more resistant to tilts. Aspheric monofocal IOLs with an anti-misalignment design can effectively resist decentration and tilt. Anti-misalignment IOLs for complicated cataract could be selected according to diopter of IOL and types and degrees of probable IOL malpositions. [J Refract Surg. 2023;39(7):446-455.].


Relationship between throwing mechanics and elbow valgus in professional baseball pitchers.
Valgus elbow stress leads to medial tension and lateral compression injuries in baseball pitchers of all ages. This study was undertaken to investigate the relationship between elbow stress in professional baseball pitchers and the kinematic parameters of pitching mechanics. This was done in an attempt to understand valgus extension overload better and in an effort to improve preventive and rehabilitative protocols. High-speed video data were collected on 40 professional pitchers in game situations during the 1998 and 1999 Cactus League season in Arizona, as part of Major League Baseball Spring Training. A multiple linear regression analysis was used to relate elbow valgus to kinematic parameters of pitching mechanics. The resulting analysis produced an adjusted multiple R2 value of 0.974, indicating that nearly 100% of the variance in valgus stress on the elbow was explained by the parameters in the regression equation. This ability to explain over 97% of the variance in valgus stress is significant. The parameters of pitching mechanics related to elbow valgus may be assessed and optimized, if necessary, in order to decrease the magnitude of elbow stress in pitching.


Comparison of Two Massively Parallel Sequencing Platforms using 83 Single Nucleotide Polymorphisms for Human Identification.
The potential of Massively Parallel Sequencing (MPS) technology to vastly expand the capabilities of human identification led to the emergence of different MPS platforms that use forensically relevant genetic markers. Two of the MPS platforms that are currently available are the MiSeq® FGx™ Forensic Genomics System (Illumina) and the HID-Ion Personal Genome Machine (PGM)™ (Thermo Fisher Scientific). These are coupled with the ForenSeq™ DNA Signature Prep kit (Illumina) and the HID-Ion AmpliSeq™ Identity Panel (Thermo Fisher Scientific), respectively. In this study, we compared the genotyping performance of the two MPS systems based on 83 SNP markers that are present in both MPS marker panels. Results show that MiSeq® FGx™ has greater sample-to-sample variation than the HID-Ion PGM™ in terms of read counts for all the 83 SNP markers. Allele coverage ratio (ACR) values show generally balanced heterozygous reads for both platforms. Two and four SNP markers from the MiSeq® FGx™ and HID-Ion PGM™, respectively, have average ACR values lower than the recommended value of 0.67. Comparison of genotype calls showed 99.7% concordance between the two platforms.


Nuclear changes in cytologic specimens obtained by CT-guided fine needle aspiration biopsies.
A light and electron microscopic study was conducted to investigate nuclear changes observed in specimens obtained from various sites by computed tomographic (CT)-guided fine needle aspiration (FNA) biopsy. These changes, which consisted of a disappearance of the nuclear chromatin and a disruption of the nuclear membrane, were found in 70% of 10 FNA specimens obtained with CT guidance, in 26% of 15 specimens obtained with fluoroscopic guidance and in 0% of 10 specimens obtained without x-ray imaging techniques. Although the number of cases studied was small and the mechanisms responsible for these changes are not clear, cytopathologists should be aware of alterations in evaluating FNA specimens obtained with the guidance of x-ray imaging techniques.


Acute phase proteins in tuberculous patients.
The serum concentrations of some acute phase proteins were determined on admission, during treatment, at the end of treatment and at 12 months after stopping treatment in 20 patients with pulmonary tuberculosis. Measurements were also made, on admission and at the end of treatment, in 19 patients with abdominal tuberculosis, and 11 children with tuberculous meningitis. All 20 patients with pulmonary TB had quiescent disease by the end of treatment and none had a bacteriological relapse during the follow-up period of 12 months. The response to treatment was considered favourable in 18 of the 19 patients with abdominal TB, and the CSF findings had returned to normal in 9 of 11 patients with TB meningitis. There was a significant decrease with treatment in the concentrations of C-reactive protein, ceruloplasmin, haptoglobin and alpha-1-acid glycoprotein in all 3 groups of patients. While there was an increase in the concentrations of transferrin in patients with pulmonary and abdominal TB, there was a significant decrease in those with TB meningitis; alpha 2-macroglobulin did not appear to function as an acute phase reactant in any of the 3 groups. Amalgamating the findings in all 3 groups of tuberculous patients, the proportions of patients with abnormal values on admission and at the end of treatment were 62% and 14% for C-reactive protein, 78% and 50% for ceruloplasmin, 86% and 26% for haptoglobin and 92% and 6% for alpha 1-acid glycoprotein, respectively.


Decompressive craniectomy for the encephalopathy of Reye's syndrome.
Report of the successful use of a decompressive craniectomy for the encephalopathy of Reye's syndrome with increased intracranial pressure. The patient had failed to respond to all medical management.


Medical marijuana for cancer.
Answer questions and earn CME/CNE Marijuana has been used for centuries, and interest in its medicinal properties has been increasing in recent years. Investigations into these medicinal properties has led to the development of cannabinoid pharmaceuticals such as dronabinol, nabilone, and nabiximols. Dronabinol is best studied in the treatment of nausea secondary to cancer chemotherapy and anorexia associated with weight loss in patients with acquired immune deficiency syndrome, and is approved by the US Food and Drug Administration for those indications. Nabilone has been best studied for the treatment of nausea secondary to cancer chemotherapy. There are also limited studies of these drugs for other conditions. Nabiximols is only available in the United States through clinical trials, but is used in Canada and the United Kingdom for the treatment of spasticity secondary to multiple sclerosis and pain. Studies of marijuana have concentrated on nausea, appetite, and pain. This article will review the literature regarding the medical use of marijuana and these cannabinoid pharmaceuticals (with emphasis on indications relevant to oncology), as well as available information regarding adverse effects of marijuana use.


Ferromagnetic fractional quantum Hall states in a valley-degenerate two-dimensional electron system.
We study a two-dimensional electron system where the electrons occupy two conduction band valleys with anisotropic Fermi contours and strain-tunable occupation. We observe persistent quantum Hall states at filling factors nu=1/3 and 5/3 even at zero strain when the two valleys are degenerate. This is reminiscent of the quantum Hall ferromagnet formed at nu=1 in the same system at zero strain. In the absence of a theory for a system with anisotropic valleys, we compare the energy gaps measured at nu=1/3 and 5/3 to the available theory developed for single-valley, two-spin systems, and find that the gaps and their rates of rise with strain are much smaller than predicted.


Influence of ERK activation on decreased chemotaxis of mature human cord blood monocyte-derived dendritic cells to CCL19 and CXCL12.
Dendritic cells (DCs) are important regulators in graft-versus-host disease (GVHD). To gain insight into cord blood (CB) DC immunology, we compared chemotactic responses of mature monocyte-derived DCs and maturation agent lipopolysaccharide (LPS)-induced signaling between CB and adult blood (AB). Mature CB DCs expressed reduced CCR7, but increased CXCR4. This was associated with reduced migratory efficiency toward both CCR7 ligand CCL19 and CXCR4 ligand CXCL12. LPS induced higher extracellular signal-regulated kinase (ERK) phosphorylation in CB than in AB DCs. Specific inhibition of ERK during CB DC maturation enhanced LPS-induced up-regulation of CCR7 and CXCR4 on CB DCs and their chemotaxis toward CCL19 and CXCL12, to a level similar to that of mature AB DCs. Overall, monocyte-derived CB DCs responded to LPS with stronger and sustained ERK activation, which negatively correlated with LPS-induced up-regulation of CCR7 and CXCR4 on CB DCs and their migratory responses. These findings may have potential relevance to better understanding DC function in CB transplantation.


A new modified Duckett urethroplasty for repair of proximal hypospadias with severe chordee: outcomes of 133 patients.
Despite the continuous development and evolution of surgical methods and techniques, proximal hypospadias remains one of the most challenging issues for pediatric urologists. This study aims to evaluate the indications and postoperative complications of our new modified Duckett urethroplasty. A total of 133 patients with proximal hypospadias who underwent repair of the modified Duckett urethroplasty from February 2016 to February 2021 were reviewed. The median age of patients was 3 years (range 1-16). All patients had severe chordee. One senior experienced pediatric urologist performed all the surgeries. Catheter was removed 14 days after the surgery. The location of the urethral meatus was proximal penile in 26 patients (19.5%), penoscrotal in 60 (45.1%), scrotal in 31 (23.3%), and perineal in 16 (12.0%). The mean length of the urethral defect was 4.5 cm (range 2.5-10). The median duration of follow-up was 46 months (range 8-67). Complications occurred in 31 patients (23.3%), including urethra-cutaneous fistula in 22 (16.5%), urethral stenosis in 7 (5.3%), and urethral diverticulum in 2 (1.5%). No recurrent chordee were found in all cases. All patients who developed complications were treated successfully at our hospital. Our modified Duckett urethroplasty showed functionally and cosmetically favorable outcomes, with a lower incidence of postoperative complications. To the best of our knowledge, the novel Duckett technique is a feasible and suitable option for patients who suffer from proximal hypospadias with severe chordee and dysplasia of the urethral plate.


Nonsteroidal antiinflammatory drugs for postoperative pain management after lumbar spine surgery: a meta-analysis of randomized controlled trials.
The authors undertook this meta-analysis to assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in addition to opioid analgesics on perioperative pain management in lumbar spine surgery. The authors searched MEDLINE, Excerpta Medica (EMBASE), The Cochrane Library, CINAHL, PsycINFO, Allied and Complementary Medicine (AMED), and Science Citation Index Expanded databases. In addition, they manually searched key journals and their references. They included randomized trials comparing the use of NSAIDs in addition to opioid analgesics versus opioid analgesics alone after posterior lumbar discectomy, laminectomy, or spinal fusion. Two independent reviewers performed an assessment of the quality of the methods. Seventeen studies comprising 400 patients who received NSAIDs in addition to opioid analgesics and 389 patients receiving opioid analgesics alone were included. Patients receiving NSAIDs in addition to opioid analgesics had lower pain scores and consumed fewer opioids than the group receiving opioid analgesics alone. There was no difference in the incidence of adverse effects. This meta-analysis provides evidence that the addition of NSAIDs to opioid analgesics in lumbar spine surgery provided better pain control than opioid analgesics alone.


Mapping the sevoflurane-binding sites of calmodulin.
General anesthetics, with sevoflurane (SF) being the first choice inhalational anesthetic agent, provide reversible, broad depressor effects on the nervous system yet have a narrow margin of safety. As characterization of low-affinity binding interactions of volatile substances is exceptionally challenging with the existing methods, none of the numerous cellular targets proposed as chief protagonists in anesthesia could yet be confirmed. The recognition that most critical functions modulated by volatile anesthetics are under the control of intracellular Ca(2+) concentration, which in turn is primarily regulated by calmodulin (CaM), motivated us for characterization of the SF-CaM interaction. Solution NMR (Nuclear Magnetic Resonance) spectroscopy was used to identify SF-binding sites using chemical shift displacement, NOESY and heteronuclear Overhauser enhancement spectroscopy (HOESY) experiments. Binding affinities were measured using ITC (isothermal titration calorimetry). SF binds to both lobes of (Ca(2+))4-CaM with low mmol/L affinity whereas no interaction was observed in the absence of Ca(2+). SF does not affect the calcium binding of CaM. The structurally closely related SF and isoflurane are shown to bind to the same clefts. The SF-binding clefts overlap with the binding sites of physiologically relevant ion channels and bioactive small molecules, but the binding affinity suggests it could only interfere with very weak CaM targets.


The impact of guest compounds on cyclodextrin aggregation behavior: A series of structurally related parabens.
Several studies have demonstrated the presence of aggregates in aqueous cyclodextrin containing solutions. The presence of guest compounds has been shown to influence this cyclodextrin aggregation process. In an attempt to gain insight into the effect of the physicochemical properties of the guest compound on 2-hydroxypropyl-β-cyclodextrin aggregation formation, a series of structurally related parabens was selected as model compounds. Using nuclear magnetic resonance spectroscopy and phase solubility studies, these parabens, differing only in side chain length, were demonstrated to form inclusion complexes with 2-hydroxypropyl-β-cyclodextrin. Additional techniques were subsequently applied to evaluate the aggregation behavior of this cyclodextrin in presence of the selected parabens. Solutions containing a broad range of 2-hydroxypropyl-β-cyclodextrin concentrations were saturated with the guest compounds and were used as test media. Results obtained from dialysis experiments, dynamic light scattering and mass spectrometry revealed a positive effect of the side chain length of the parabens on aggregate formation: in presence of heptylparaben, more and larger aggregates were observed than in presence of parabens with shorter side chains such as methyl- and butylparaben. No clear connection could be demonstrated between the cyclodextrin concentration and the extent of aggregate formation in presence of the guest compound.


Vasospasms of the radial artery after the transradial approach for coronary angiography and angioplasty.
We examined vasospasms of the radial artery after a transradial approach was used for coronary angiography or angioplasty. In forty-eight patients (39 males and 9 females), arteriography of the radial artery was initially performed just after the transradial approach was used for coronary angiography and/or angioplasty. Then, five months later, a second arteriography of the radial artery was obtained after a transbrachial approach was used for coronary angiography. First and second arteriographies were compared to evaluate vaso-spasms of the radial artery. In the present study, more than 75% stenosis in the radial artery, 25-75% stenosis, and less than 25% stenosis were tentatively defined as severe spasms, moderate spasms, and mild spasms, respectively. In arteriographic studies on the radial artery, twenty-four patients (50%) had severe radial artery spasms, eleven patients (23%) had moderate spasms, and thirteen patients (27%) had mild spasms. The diameters of both the proximal and distal radial arteries in the severe spasm group were significantly smaller than those in the mild and moderate spasm groups (proximal site: severe group 2.39 +/- 0.70 mm versus mild group 2.98 +/- 0.46 mm, P < 0.05, and moderate group 2.96 +/- 0.77 mm, P < 0.05, distal site: severe group 2.26 +/- 0.60 mm versus mild group 2.73 +/- 0.47 mm, P < 0.05, and moderate group 2.86 +/- 0.71 mm, P < 0.05). We concluded that vasospasms of the radial artery occurred in most patients after the transradial approach. Furthermore, severe radial spasms were strongly correlated with the size of the diameter of the artery.


Physiological activation of Akt by PHLPP1 deletion protects against pathological hypertrophy.
To examine the role of physiological Akt signalling in pathological hypertrophy through analysis of PHLPP1 (PH domain leucine-rich repeat protein phosphatase) knock-out (KO) mice. To investigate the in vivo requirement for 'physiological' control of Akt activation in cardiac growth, we examined the effect of deleting the Akt phosphatase, PHLPP, on the induction of cardiac hypertrophy. Basal Akt phosphorylation increased nearly two-fold in the cardiomyocytes from PHLPP1 KO mice and physiological hypertrophy induced by swimming exercise was accentuated as assessed by increased heart size and myocyte cell area. In contrast, the development of pathophysiological hypertrophy induced by pressure overload and assessed by increases in heart size, myocyte cell area, and hypertrophic gene expression was attenuated. This attenuation coincided with decreased fibrosis and cell death in the KO mice. Cast moulding revealed increased capillary density basally in the KO hearts, which was further elevated relative to wild-type mouse hearts in response to pressure overload. In vitro studies with isolated myocytes in co-culture also demonstrated that PHLPP1 deletion in cardiomyocytes can enhance endothelial tube formation. Expression of the pro-angiogenic factor VEGF was also elevated basally and accentuated in response to transverse aortic constriction in hearts from KO mice. Our data suggest that enhancing Akt activity by inhibiting its PHLPP1-mediated dephosphorylation promotes processes associated with physiological hypertrophy that may be beneficial in attenuating the development of pathological hypertrophy.


Opioid Receptor Modulators with a Cinnamyl Group.
To obtain selective and potent opioid receptor ligands, we synthesized dehydro derivatives of alvimopan and found compound (28f), a selective but modest affinity MOR antagonist weaker than alvimopan (1). We replaced the arylpiperidine unit by an arylpiperazine to obtain the 1-(α-carboxycinnamyl)-4-arylpiperazines like 13h, which to our surprise had no MOR or DOR activity but was a KOR agonist with moderate affinity. In contrast, literature examples of arylpiperazines 4 and 5 were reported to be pan opioid receptor antagonists, while 6 was a MOR agonist. Two compounds (13l and 11b) showed analgesic response in tail flick test which was blocked by pretreatment with norbinaltorphimine (norBNI). Among 10 1-(α-carboxycinnamyl)-4-arylpiperidines, compound 28g and five others were specific MOR antagonists. Interestingly, compound 26b of this series was found to be more potent than naloxone but weaker than 1. Docking studies have explained differential activities of the above piperazines and piperidines.


[Regional Differences and Determinants of Self-rated Health in Elderly].
To determine differences of self-rated health in elderly people across geographic regions of China, and to identify factors influencing self-rated health of elderly. Ordered logistic modeling was performed using the China Health and Retirement Longitudinal Study (CHARLS) data in 2013. Elderly people resided in Eastern China had better self-rated health than their counterparts residing in Middle (partial regression coefficient 0.252, P < 0.01) and Western (partial regression coefficient 0.338, P < 0.001) China. Sex, residency, education, per capita consumption expenditure, smoking and drinking, social participation, chronic diseases, and life satisfaction were identified as associated with self-rated health of elderly. There are regional differences in self-rated health of elderly. Policy priorities should be given to Middle and Western China, with more health resources being allocated to those regions. Regional economic and educational inequalities need to be addressed. Healthy lifestyle should be promoted.


Whirling in the late Permian: ancestral Gyrinidae show early radiation of beetles before Permian-Triassic mass extinction.
Gyrinidae are a charismatic group of highly specialized beetles, adapted for a unique lifestyle of swimming on the water surface. They prey on drowning insects and other small arthropods caught in the surface film. Studies based on morphological and molecular data suggest that gyrinids were the first branch splitting off in Adephaga, the second largest suborder of beetles. Despite its basal position within this lineage and a very peculiar morphology, earliest Gyrinidae were recorded not earlier than from the Upper Triassic. Tunguskagyrus. with the single species Tunguskagyrus planus is described from Late Permian deposits of the Anakit area in Middle Siberia. The genus is assigned to the stemgroup of Gyrinidae, thus shifting back the minimum age of this taxon considerably: Tunguskagyrus demonstrates 250 million years of evolutionary stability for a very specialized lifestyle, with a number of key apomorphies characteristic for these epineuston predators and scavengers, but also with some preserved ancestral features not found in extant members of the family. It also implies that major splitting events in this suborder and in crown group Coleoptera had already occurred in the Permian. Gyrinidae and especially aquatic groups of Dytiscoidea flourished in the Mesozoic (for example Coptoclavidae and Dytiscidae) and most survive until the present day, despite the dramatic "Great Dying" - Permian-Triassic mass extinction, which took place shortly (in geological terms) after the time when Tunguskagyrus lived. Tunguskagyrus confirms a Permian origin of Adephaga, which was recently suggested by phylogenetic "tip-dating" analysis including both fossil and Recent gyrinids. This also confirms that main splitting events leading to the "modern" lineages of beetles took place before the Permian-Triassic mass extinction. Tunguskagyrus shows that Gyrinidae became adapted to swimming on the water surface long before Mesozoic invasions of the aquatic environment took place (Dytiscoidea). The Permian origin of Gyrinidae is consistent with a placement of this highly derived family as the sister group of all remaining adephagan groups, as suggested based on morphological features of larvae and adults and recent analyses of molecular data.


Prevalence of congenital heart defects associated with Down syndrome in Korea.
Congenital heart defect (CHD) is common in infants with Down syndrome (DS), which is the principle cause of mortality. However, there is no data available for the frequency and types of CHD in infants with DS in Korea. We investigated the frequency of CHD in infants with DS in Korea. After the survey on birth defects was conducted throughout the country, the prevalence of CHD in DS in 2005-2006 was calculated. This study was conducted based on the medical insurance claims database of the National Health Insurance Corporation. The number of total births in Korea was 888,263 in 2005-2006; of them, 25,975 cases of birth defects were identified. The prevalence of DS was 4.4 per 10,000 total births, accounting for 1.5% of all birth defects. Of the 394 infants with DS, 224 (56.9%) had a CHD. Atrial septal defect was the most common defect accounting for 30.5% of DS followed by ventricular septal defect (19.3%), patent duct arteriosus (17.5%), and atrioventricular septal defect (9.4%). Our study will be helpful to demonstrate the current status of DS and to identify the distribution of CHD in infants with DS in Korea.


Evaluating a GPS-based transportation device to support independent bus travel by people with intellectual disability.
We examined the utility of a PDA-based software system with integrated GPS technology for providing location-aware visual and auditory prompts to enable people with intellectual disability to successfully navigate a downtown bus route. Participants using the system were significantly more successful at completing a bus route than were people in a control group, who used a map and verbal directions. Further, when using the GPS-based system, 73% of participants successfully rang the bell and exited the bus at the right stop compared with only 8% of the control group. This finding was observed for individuals attempting to follow a new bus route for the first time and get off the bus at a previously unknown location.


Correlation Study of the Most Important Environmental Influencing Factors on the Razi MMR Vaccine.
Measles, mumps, and rubella (MMR) are among the most important viral infectious diseases in Iran and neighboring countries. After using a trivalent vaccine for these three diseases for a long time, in recent years, these diseases have been significantly controlled in Iran. One of the important points of storing the vaccine is that the vaccine strains are highly temperature-sensitive viruses. Due to tropical climatic conditions in Iran, the cold chain may not be achievable during the storage and transmission of the MMR vaccine. Therefore, the efficacy of the vaccine may be affected. This study aimed to evaluate the MMR vaccine potency at different temperatures (stress tests) and frequent light exposures. All quality control tests in the form of stability studies were performed on the samples from three consecutive batches produced during a full-scale Razi production. The samples were stored at 2-8, 22-25, 35-37, and 42-45°C in specific time intervals, exposed to frequent light, and underwent freezing/thawing conditions. According to the results, the storage of the vaccine at high temperatures caused a decrease in potency and increased moisture content in the vaccine vials. The best temperature for maintenance and transportation of MMR is 2-8°C. The time and frequency of light exposure may affect the vaccine potency. Based on the sensitivity of the vaccine strains to environmental conditions, the development of plans for storage and transportation of vaccines in different situations and training the vaccine injection staff seem necessary.


Human Sco1 functional studies and pathological implications of the P174L mutant.
The pathogenic mutant (P174L) of human Sco1 produces respiratory chain deficiency associated with cytochrome c oxidase (CcO) assembly defects. The solution structure of the mutant in its Cu(I) form shows that Leu-174 prevents the formation of a well packed hydrophobic region around the metal-binding site and causes a reduction of the affinity of copper(I) for the protein. K(D) values for Cu(I)WT-HSco1 and Cu(I)P174L-HSco1 are approximately 10(-17) and approximately 10(-13), respectively. The reduction potentials of the two apo proteins are similar, but slower reduction/oxidation rates are found for the mutant with respect to the WT. The mitochondrial metallochaperone in the partially oxidized Cu(1)(I)Cox17(2S-S) form, at variance with the fully reduced Cu(4)(I)Cox17, interacts transiently with both WT-HSco1 and the mutant, forming the Cox17/Cu(I)/HSco1 complex, but copper is efficiently transferred only in the case of WT protein. Cu(1)(I)Cox17(2S-S) indeed has an affinity for copper(I) (K(D) approximately 10(-15)) higher than that of the P174L-HSco1 mutant but lower than that of WT-HSco1. We propose that HSco1 mutation, altering the structure around the metal-binding site, affects both copper(I) binding and redox properties of the protein, thus impairing the efficiency of copper transfer to CcO. The pathogenic mutation therefore could (i) lessen the Sco1 affinity for copper(I) and hence copper supply for CcO or (ii) decrease the efficiency of reduction of CcO thiols involved in copper binding, or both effects could be produced by the mutation.


Molecular Orientation and Energy Transfer Dynamics of a Metal Oxide Bound Self-Assembled Trilayer.
Self-assembly of molecular multilayers via metal ion linkages has become an important strategy for interfacial engineering of metalloid and metal oxide (MOx) substrates, with applications in numerous areas, including energy harvesting, catalysis, and chemical sensing. An important aspect for the rational design of these multilayers is knowledge of the molecular structure-function relationships. For example, in a multilayer composed of different chromophores in each layer, the molecular orientation of each layer, both relative to the adjacent layers and the substrate, influences the efficiency of vectorial energy and electron transfer. Here, we describe an approach using UV-vis attenuated total reflection (ATR) spectroscopy to determine the mean dipole tilt angle of chromophores in each layer in a metal ion-linked trilayer self-assembled on indium-tin oxide. To our knowledge, this is the first report demonstrating the measurement of the orientation of three different chromophores in a single assembly. The ATR approach allows the adsorption of each layer to be monitored in real-time, and any changes in the orientation of an underlying layer arising from the adsorption of an overlying layer can be detected. We also performed transient absorption spectroscopy to monitor interlayer energy transfer dynamics in order to relate structure to function. We found that near unity efficiency, sub-nanosecond energy transfer between the third and second layer was primarily dictated by the distance between the chromophores. Thus, in this case, the orientation had minimal impact at such proximity.


[Kinetics of the appearance of HLA-DR antigens on human alloactivated T lymphocytes and the demonstration of new antigenic determinants].
By studying serologically the appearance of HLA-DR determinants on T lymphocytes activated by a mixed lymphocyte culture, we have been able to demonstrate the existence of a new class of antigenic determinants distinct from classical HLA-DR antigens. Indeed, some monospecific anti-DR sera were cytotoxic from some alloactivated T cells, though not directed against their HLA-DR specificity. The absorption of these anti-sera on B lymphocytes bearing the HLA-DR antigen against which they were directed, did not remove their reactivity on alloactivated T lymphocytes. The absorption of the same anti-sera on activated T lymphocytes did not affect their anti-DR reactivity. This study shows the existence of new antigenic determinants expressed by T lymphocytes during their activation: alloactivated T lymphocyte antigens (AATL).


Attachment of the PSGL-1 cytoplasmic domain to the actin cytoskeleton is essential for leukocyte rolling on P-selectin.
P-selectin glycoprotein ligand-1 (PSGL-1) serves as the leukocyte ligand for P-selectin, and many of the structural features of its ectodomain required for interactions with P-selectin have been uncovered. In contrast, the function of the highly conserved PSGL-1 cytoplasmic domain has not been explored. Stable transfectants expressing similar levels of either wild-type PSGL-1 or truncated PSGL-1 in which only 4 cytoplasmic residues were retained (designated PSGL-1 Delta cyto), were analyzed. Transfectants expressing full-length PSGL-1 rolled well on P-selectin. In contrast, rolling was almost completely absent in cells transfected with PSGL-1 Delta cyto, even at low shear. Importantly, cells expressing truncated PSGL-1 were able to bind soluble P-selectin and to bind COS cells overexpressing P-selectin, demonstrating that the P-selectin binding site on the PSGL-1 Delta cyto transfectants was intact and was capable of recognizing P-selectin. Impaired rolling by PSGL-1 Delta cyto transfectants was not due to alterations in subcellular localization because both wild-type and truncated PSGL-1 had similar surface distributions on K562 transfectants. Treatment of cells expressing native PSGL-1 with actin cytoskeletal toxins inhibited adhesion in a dose-dependent way. PSGL-1 was associated with the actin cytoskeleton, and this interaction was greatly impaired in PSGL-1 Delta cyto- expressing cells. The PSGL-1 cytoplasmic domain interacted selectively with the ezrin/radixin/moesin (ERM) protein moesin, but not with other ERM proteins or several other cytoskeletal linker proteins. Pharmacologic disruption of interactions between moesin and F-actin in cells expressing PSGL-1 resulted in a dose-dependent inhibition of rolling on P-selectin. Thus, attachment of PSGL-1 to the leukocyte cortical cytoskeleton is essential for leukocyte rolling on P-selectin.


Development and validation of the medication regimen complexity index.
Medication regimen attributes, such as the number of drugs, dosage frequency, administration instructions, and the prescribed dosage forms, have been shown to influence patient outcomes. No single tool for quantifying the complexity of general medication regimens has been published in the medical literature. To develop and validate a tool to quantify the complexity of prescribed medication regimens. Literature findings and the expertise of the authors were used for developing the tool. Eight pharmacy researchers helped in establishing the tool's face and content validity. The new tool was tested on 134 medication regimens from patients with moderate to severe chronic obstructive pulmonary disease. Six regimens with a spread of scores on the tool were presented to a 5-member expert panel that subjectively ranked these regimens to confirm the tool's criterion-related validity. The relationships between scores on the tool and various independent variables were tested to judge the tool's construct validity. Two raters scored 25 regimens using the tool to test its inter-rater and test-retest reliabilities. A 65-item Medication Regimen Complexity Index (MRCI) was developed. The expert panel had strong agreement (Kendall's W = 0.8; p = 0.001) on their individual rankings of the 6 regimens. The panel's consensus ranking had perfect correlation with the MRCI ranking. The total MRCI score had significant correlation with the number of drugs in the regimen (Spearman's Rho = 0.9; p < 0.0001), but not with the age and gender of the patients. Inter-rater and test-retest reliabilities for the total score and scores for individual sections on the MRCI were > or = 0.9. The MRCI is a reliable and valid tool for quantifying drug regimen complexity with potential applications in both practice and research.


A randomized controlled behavioral intervention trial to improve medication adherence in adult stroke patients with prescription tailored Short Messaging Service (SMS)-SMS4Stroke study.
The effectiveness of mobile technology to improve medication adherence via customized Short Messaging Service (SMS) reminders for stroke has not been tested in resource poor areas. We designed a randomized controlled trial to test the effectiveness of SMS on improving medication adherence in stroke survivors in Pakistan. This was a parallel group, assessor-blinded, randomized, controlled, superiority trial. Participants were centrally randomized in fixed block sizes. Adult participants on multiple medications with access to a cell phone and stroke at least 4 weeks from onset (Onset as defined by last seen normal) were eligible. The intervention group, in addition to usual care, received reminder SMS for 2 months that contained a) Personalized, prescription tailored daily medication reminder(s) b) Twice weekly health information SMS. The Health Belief Model and Social Cognitive theory were used to design the language and content of messages. Frontline SMS software was used for SMS delivery. Medication adherence was self-reported and measured on the validated Urdu version of Morisky Medication Adherence Questionnaire. Multiple linear regression was used to model the outcome against intervention and other covariates. Analysis was conducted by intention-to-treat principle. Two hundred participants were enrolled. 38 participants were lost to follow-up. After 2 months, the mean medication score was 7.4 (95 % CI: 7.2-7.6) in the intervention group while 6.7 (95 % CI: 6.4-7.02) in the control group. The adjusted mean difference (Δ) was 0.54 (95 % CI: 0.22-0.85). The mean diastolic blood pressure in the intervention group was 2.6 mmHg (95 % CI; -5.5 to 0.15) lower compared to the usual care group. A short intervention of customized SMS can improve medication adherence and effect stroke risk factors like diastolic blood pressure in stroke survivors with complex medication regimens living in resource poor areas. Clinicaltrials.gov NCT01986023 last accessed at https://clinicaltrials.gov/ct2/show/NCT01986023.


Self-reported health following percutaneous coronary intervention: results from a cohort followed for 3 years with multiple measurements.
Improvements in the treatment of coronary heart disease have increased the number of patients living with a chronic heart disease. Patient-reported outcomes are required to adequately describe prognosis. We report self-rated health in a population-based cohort of patients with coronary heart disease treated with percutaneous coronary intervention (PCI). Over 3 years, we followed 1,726 patients under 65 years treated with PCI with eight repetitive questionnaires. With the use of multiple imputation, we described the course of self-rated health using the short form 12-item survey's mental component summary (MCS) and physical component summary (PCS) and analyzed adjusted differences by sex, age, educational level, indication for PCI, and left ventricular ejection fraction along with an analysis of decrease in health status. MCS scores increased during follow-up, while PCS scores were stable over time. Men rated higher in MCS and PCS than women, and older patients rated higher in MCS than younger. Other differences were negligible. Younger age was identified as a risk factor for marked decrease in mental health over time. In a complete population-based cohort of PCI patients with multiple measurements, we found improvements in mental, but not physical health over time. Demographic differences in health were larger than disease-related differences.


[Contents and spatial distribution patterns of heavy metals in fFarmland soils of Fuxin City].
A total of 180 farmland soil samples were collected from the suburbs of Fuxin City, Liaoning Province, to investigate the contents and spatial distribution patterns of Cu, Zn, As and Ni, with the effects of mining on their accumulation and spatial distribution in test farmland soils discussed. The results indicated that in study area, farmland soils had an accumulation of Cu, Zn and Ni, with the geometric mean concentrations higher than the background values. Among the soils planted with different crops, vegetable soil had significantly higher contents of Cu, Zn and As than grain crop soil. The spatial distribution of four test metals showed the same pattern of urban > suburban, and the regions with high concentrations of heavy metals were well overlapped with mining areas, suggesting that mining activities might be one of the most important source of heavy metals in the farmland soils. The rapid increase of animal manure also contributed to the import of pollutants to farmland soils to some degree. The potential risks of soil heavy metals pollution should be considered in the arrangement of local agricultural and animal husbandry productions.


Influence of day of oestrus on egg viability and comparative efficiency of in vitro fertilization in domestic cats in natural or gonadotrophin-induced oestrus.
Thirty-six domestic cats received 100 iu hCG (i.m.) on day 1, 2 or 3 of a natural, behavioural oestrus. Twenty-two anoestrous cats were injected with 150 iu pregnant mares' serum gonadotrophin (PMSG; i.m.) followed 84 h later by 100 iu hCG. Twenty-four to 26 h after hCG, all cats were examined laparoscopically to determine the number of ovarian follicles and to recover follicular eggs. Mature eggs were cultured with conspecific spermatozoa and examined 30 h later for cleavage. Within the natural oestrus group, cats on day 1 produced fewer (P < 0.05) follicles and total eggs than females on day 2 or 3, and 88.9% of the day 1 eggs were degenerate or immature and unsuitable for in vitro fertilization (IVF). Although only 54.5% of the cats in the PMSG/hCG group exhibited overt oestrus, mean (+/- SEM) numbers of follicles (9.7 +/- 0.8) and oocytes recovered (8.7 +/- 0.8) were at least twofold greater (P < 0.001) than those measured in the natural oestrus group (3.7 +/- 0.6; 3.4 +/- 0.6, respectively) or subgroups on day 2 (3.7 +/- 0.4; 3.3 +/- 0.4) and day 3 (5.7 +/- 0.8; 5.3 +/- 0.8). Overall, the proportion of eggs cleaving in vitro was similar (P > 0.05) between the natural oestrus group (48.3%) and the PMSG/hCG group (50.9%), but the latter group produced more than twice the number of embryos per donor. Embryo quality was unaffected (P > 0.05) by day of hormone treatment, and more than 80% of all two-cell embryos were rated good-to-excellent quality.(ABSTRACT TRUNCATED AT 250 WORDS)


Plasmacytoid dendritic cells (pDCs) from HIV controllers produce interferon-α and differentiate into functional killer pDCs under HIV activation.
Human immunodeficiency virus (HIV) controllers spontaneously control viremia and CD4 T-cell depletion in contrast to viremic patients. After HIV exposure, plasmacytoid dendritic cells (pDCs) produce high levels of interferon alpha (IFN-α) and express the apoptotic ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand). Simian models have shown that prolonged high levels of IFN-α production could be responsible for AIDS progression. We studied pDC activation in response to human immunodeficiency virus (HIV) using flow cytometry and 3D microscopy. We show here that pDCs from controller patients produced higher levels of IFN-α in response to HIV than pDCs from viremic patients but similar levels to pDCs from healthy donors. Because binding of HIV to CD4 is essential for pDC activation, the low CD4 expression by pDCs from viremic patients may explain the weak IFN-α response to HIV. Three-dimensional microscopy revealed that pDCs from controllers and healthy donors expressed intracellular TRAIL that is relocalized to the membrane after HIV exposure. In contrast, pDCs from viremic patients expressed membrane TRAIL without any stimulation. We demonstrate that, in response to HIV, pDCs from controller patients produce IFN-α, express membrane TRAIL, and induce apoptosis of T-cell lines.


The Relationship Between Knowledge, Attitude, Practice, and Fall Prevention for Childhood in Shanghai, China.
Early childhood fall is a pressing global public health problem and one of the leading causes of child injury. China has a high proportion of children and a high burden of illness from falls. Therefore, educational interventions to prevent childhood fall would be beneficial. We used the outcome of knowledge, attitude and practice questionnaire, which was conducted by Pudong New District of Shanghai Municipal Government, to summarize demographic and baseline characteristics grouped by intervention or not, and analyzed descriptive statistics of continuous and categorical variables. A logistic stepwise function model was established to study the influence of different covariables on the degree of injury, and AIC/BIC/AICC was used to select the optimal model. Finally, we carried out single-factor analysis and established a multifactor model by the stepwise function method. Attitude and actual behavior scores had significant differences. The intervention and control groups had 20.79 ± 3.20 and 20.39 ± 2.89 attitude scores, respectively. Compared to the control group (5.97 ± 1.32), the intervention group had higher actual behavior scores (5.75 ± 1.50). In the univariate analysis results, fathers' education level, mothers' education level, actual behavior and what cares for children had a significant influence on whether children got injured. In multivariate analysis, attitude had a positive influence on whether injured [odds ratio: 1.13 (1.05-1.21), P < 0.001]. Educational intervention for children and their guardians can effectively reduce the risk of childhood falls, and changes in behavior and attitude are the result of educational influence. Education of childhood fall prevention can be used as a public health intervention to improve children's health.


Purification and characterization of calcium-binding soybean protein hydrolysates by Ca2+/Fe3+ immobilized metal affinity chromatography (IMAC).
Soybean protein hydrolysates (SPHs) can bind calcium in order to form soluble peptide-calcium complexes. However, amino acid composition and structural characteristics of the calcium chelating SPHs are still unclear. This study separated SPHs with calcium and iron immobilized metal affinity chromatography (IMAC), and examined the effects of SPHs with different amino acid composition on calcium binding capacity. Three fractions (FFe-1, FFe-2 and FFe-3) isolated with IMAC-Fe(3+) were shown possessing increased Glu, Gln, Lys and Pro content from FFe-1 to FFe-3, and improved amount of bound calcium. Furthermore, the fractions adsorbed on IMAC-Ca(2+) (Fe(3+)) were separated and identified with reverse-phase (RP)-HPLC and MALDI-TOF MS/MS. The results showed that the sequence of peptides from FCa-2 and FFe-3 fractions was DEGEQPRPFPFP.


Agreement between adolescents and parents/caregivers in rating the impact of malocclusion on adolescents' quality of life.
To assess the agreement between adolescents and their parents/caregivers regarding the impact of malocclusion on adolescents' oral health-related quality of life (OHRQoL). A consecutive sample of 141 adolescent and parent/caregiver pairs was selected. Adolescents answered the short version of the Child Perceptions Questionnaire (CPQ11-14), while parents answered the Parental-Caregiver Perceptions Questionnaire (P-CPQ). The CPQ11-14 and the P-CPQ have 14 items in common that are organized through four subscales: oral symptoms (OS), functional limitations (FL), emotional well-being (EW), and social well-being (SW). Agreement on the overall score and agreement on the subscales were determined using comparison and correlation analysis. The comparison analysis was carried out by comparing the mean directional and absolute differences, and the correlation analysis was performed using the intraclass correlation coefficient (ICC). A total of 135 pairs of adolescents and parents/caregivers agreed to answer the questionnaires, providing a response rate of 95.7%. The mean age of the adolescents was 11.50 years. The mean directional difference was significant for the OS (P < .001) and FL (P = .040) subscales as well as for the overall score (P = .007). Adolescents' reports were higher than parents/caregivers' reports. The mean absolute difference for the overall score was 7.26, representing 12.9% of the maximum possible overall score. The ICC was 0.16 for the overall score, indicating poor agreement. Poor agreement was observed between adolescents and their parents/caregivers in rating the impact of malocclusion on adolescents' OHRQoL.


Suicidal ideation and suicide attempts among human immunodeficiency virus-infected adults: differences in risk factors and their implications.
Many studies have investigated risk factors for suicidal ideation and suicide attempt; however, most have failed to show differences in risk factors between suicidal ideation and suicide attempt among the human immunodeficiency virus (HIV)-infected population. This study was designed to identify differences in risk factors between suicidal ideation and suicide attempts among HIV-infected adults in Seoul. A face-to-face survey of 457 HIV-infected adults was conducted by the Seoul Metropolitan Government in 2013. Multivariate logistic regression analysis was used to identify factors associated with suicidal ideation and suicide attempt. Among 422 participants, 44% had suicidal ideation, and 11% had suicide attempts. The independent risk factors for suicidal ideation were young and middle age, living with someone, history of AIDS-defining opportunistic disease, history of treatment for depression, lower social support, and psychological status. Beneficiaries of National Medical Aid, economic barriers to treatment, history of treatment for depression, and lower psychological status were independently associated with suicide attempts. Patients with HIV in Korea were treated without cost in some centers. Thus, experiencing an economic barrier to treatment might be due in part to ignorance of HIV care policies. Our findings indicate that suicide attempts are associated with socioeconomic factors and information inequality regarding medical care. In conclusion, suicidal ideation closely associated with the psychosocial factors, whereas suicide attempt demonstrates a stronger association with socioeconomic factors. Suicide prevention measures should be implemented to provide information to help HIV-infected patients.


Effects of monascin on anti-inflammation mediated by Nrf2 activation in advanced glycation end product-treated THP-1 monocytes and methylglyoxal-treated wistar rats.
Hyperglycemia is associated with advanced glycation end products (AGEs). This study was designed to evaluate the inhibitory effects of monascin on receptor for advanced glycation end product (RAGE) signal and THP-1 monocyte inflammation after treatment with S100b, a specific ligand of RAGE. Monascin inhibited cytokine production by S100b-treated THP-1 monocytes via up-regulation of nuclear factor-erythroid 2-related factor-2 (Nrf2) and alleviated p47phox translocation to the membrane. Methylglyoxal (MG, 600 mg/kg bw) was used to induce diabetes in Wistar rats. Inhibitions of RAGE and p47phox by monascin were confirmed by peripheral blood mononuclear cells (PBMCs) of MG-induced rats. Silymarin (SM) was used as a positive control group. It was found that monascin promoted heme oxygenase-1 (HO-1) expression mediated by Nrf2. Suppressions of AGEs, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-β) in serum of MG-induced rats were attenuated in the monascin administration group treated with retinoic acid (RA). RA treatment resulted in Nrf2 inactivation by increasing RA receptor-α (RARα) activity, suggesting that RA acts as an inhibitor of Nrf2. The results showed that monascin exerted anti-inflammatory and antioxidative effects mediated by Nrf2 to prevent the development of diseases such as type 2 diabetes caused by inflammation.


The neural regions sustaining episodic encoding and recognition of objects.
In this functional MRI experiment, encoding of objects was associated with activation in left ventrolateral prefrontal/insular and right dorsolateral prefrontal and fusiform regions as well as in the left putamen. By contrast, correct recognition of previously learned objects (R judgments) produced activation in left superior frontal, bilateral inferior frontal, and right cerebellar regions, whereas correct rejection of distractor objects (N judgments) was associated with activation in bilateral prefrontal and anterior cingulate cortices, in right parietal and cerebellar regions, in the left putamen, and in the right caudate nucleus. The R minus N comparison showed activation in the left lateral prefrontal cortex and in bilateral cingulate cortices and precunei, while the N minus R comparison did not reveal any positive signal change. These results support the view that similar regions of the frontal lobe are involved in episodic encoding and retrieval processes, and that the successful episodic retrieval of newly learned objects is mainly based on a frontoparietal network.


Second Axillary Sentinel Lymph Node Biopsy for Breast Tumor Recurrence: Experience of the European Institute of Oncology.
This retrospective study aimed to determine the feasibility, accuracy, and recurrence rates of lymphoscintigraphy and the new sentinel lymph node biopsy (SLNB) for patients with ipsilateral breast tumor recurrences who were treated previously with conservative surgery and had negative SLNB results. The study was conducted at the European Institute of Oncology in Milan and included 212 patients with the diagnosis of operable local breast cancer recurrence. They had been treated previously with conservative surgery and showed negative SLNB results. They subsequently underwent additional breast surgery and a second SLNB between May 2001 and December 2011. Preoperative lymphoscintigraphy demonstrated at least one new axillary sentinel lymph node (SLN) in 207 patients (97.7 %), whereas no drainage was observed in five patients (2.3 %). One or more SLNs were surgically removed from 196 of the 207 patients. Isolation of SLNs from the remaining 11 patients could not be accomplished. The success rate for the SLNB was 92.5 %. Extra-axillary drainage pathways were visualized in 17 patients (8 %). The annual axillary recurrence rate after a median follow-up period of 48 months was 0.8 %, and the cumulative incidence of axillary recurrence at 5 years was 3.9 %. A second SLNB should be considered for patients with operable local breast tumor recurrence who underwent conservative surgery and had negative SLNB results. The procedure is technically feasible and accurate for selected patients.


Ischemic stroke in young adults.
Although the clinical approach to the young adult stroke patient is similar to that of an older adult, several important differences exist. The purpose of this article is to concisely review the epidemiology, pathophysiology, risk factors, clinical manifestations, diagnostic methods and current treatment options for the young adult ischemic stroke patient. Evidence clearly indicates that the incidence ischemic stroke in young adults is on the rise. A variety of factors are implicated, including an increased burden of classic and emerging vascular risk factors, and improved stroke detection, among other causes. Improved awareness, prevention and successful treatment of the young adult stroke patient is of great importance, particularly given the major long-term socioeconomic impact strokes have on the patient, their family and society at large. In this review, we focus on the latest epidemiologic, diagnostic and treatment paradigms to improve physician awareness and optimize outcomes in young adult ischemic stroke patients. An overview of the clinical presentations of various stroke syndromes is described, emphasizing key causes physicians should consider, as well as providing recommendations regarding evaluation and treatment. Important causes including dissection and inflammatory and noninflammatory vasculopathies are emphasized. The diagnoses of cerebral venous thromboses, cardioembolic stroke and paradoxical emboli are also discussed. The effects of established and emerging risk factors on large and small vessel disease, as well as genetic contributions, are also highlighted.


Lack of effect of percutaneous transluminal renal angioplasty on nocturnal hypotension in renovascular hypertensive patients.
To investigate whether nocturnal blood pressure fall is blunted in renovascular hypertension and can therefore be used as a diagnostic criterion for this condition. In 14 renovascular hypertensive patients (age 43.8+/-2.1 years, mean+/-SEM, clinic blood pressure 173.6+/-3.7 mmHg systolic and 109.0+/-2.0 mmHg diastolic) and in 14 age- and blood pressure-matched essential hypertensive controls 24 h ambulatory blood pressure was measured after washout from drug treatment, during angiotensin converting enzyme inhibitor treatment and, in renovascular hypertension, also after percutaneous transluminal renal angioplasty. The 24 h average systolic and diastolic blood pressures were 146.4+/-5.7 and 97.5+/-3.6 mmHg in renovascular and 144.3+/-1.2 and 98.0+/-2.2 mmHg in essential hypertensive patients. The angiotensin converting enzyme inhibitor treatment reduced 24 h average systolic and diastolic blood pressures by 8.5% and 9.7% in the renovascular and by 8.3% and 10.8% in the essential hypertensive group. Greater systolic and diastolic blood pressure reductions (-18.2% and -18.1%) were observed in renovascular hypertensive patients after percutaneous transluminal renal angioplasty. Blood pressure fell by about 10% during the night and the fall was similar in renovascular and in essential hypertensive patients. In the former group, nocturnal hypotension was similar after washout, during angiotensin converting enzyme inhibitor treatment and after percutaneous transluminal renal angioplasty. Similar results were obtained for nocturnal bradycardia. Nocturnal blood pressure fall is equally manifest in renovascular and essential hypertension. The removal of the renal artery stenosis and blood pressure normalization do not enhance this phenomenon. Nocturnal hypotension seems therefore to be unaffected by renovascular hypertension.


Safeguarding health care workers.
Editor's note: The International Council of Nurses (ICN) is a federation of more than 130 international nursing organizations. We invited the ICN to contribute a periodic column highlighting some of its initiatives to address global nursing issues. For more information, see the ICN Web site at www.icn.ch.


Asthma and rhinitis in schoolchildren: the impact of allergic sensitization to aeroallergens.
This study aimed to evaluate the prevalence of asthma and rhinitis in schoolchildren living in the Genoa area by using a validated questionnaire and to investigate the prevalence of sensitizations using skin prick tests. An ATS modified questionnaire was given to 781 schoolchildren (all of them aged between 11 and 14 years) resident in the Genoa area. The main outcome of the present survey demonstrates a high prevalence of sensitized children (40.7%). Asthma and rhinitis prevalences are very high, mainly concerning the lifetime diagnosis. Actual asthma prevalence is about 6%, confirming ISAAC results, but rhinitis prevalence is notably higher and there is no difference between seasonal and perennial forms. Mites are the most important cause of sensitization and pollens are more frequently the cause of polysensitization. A distinct percentage of the asthmatic children and a higher percentage of rhinitic children are nonallergic. On the other hand, about one third of the sensitized children are without symptoms: They may be considered as subjects at risk of developing clinical respiratory diseases later. In conclusion, this study shows the importance of evaluating the existence of atopy, since there are many subjects with asthma and rhinitis who are nonallergic, and subjects at risk of developing respiratory allergies may be detected.


Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis.
A significant need for reliable and accurate cancer diagnostics and prognosis compels the search for novel biomarkers that would be able to discriminate between indolent and aggressive tumors at the early stages of disease. The aim of this work was identification of potential diagnostic biomarkers for characterization of different types of prostate tumors. NotI-microarrays with 180 clones associated with chromosome 3 genes/loci were applied to determine genetic and epigenetic alterations in 33 prostate tumors. For 88 clones, aberrations were detected in more than 10% of tumors. The major types of alterations were DNA methylation and/or deletions. Frequent methylation of the discovered loci was confirmed by bisulfite sequencing on selective sampling of genes: FGF12, GATA2, and LMCD1. Three genes (BHLHE40, BCL6, and ITGA9) were tested for expression level alterations using qPCR, and downregulation associated with hypermethylation was shown in the majority of tumors. Based on these data, we proposed the set of potential biomarkers for detection of prostate cancer and discrimination between prostate tumors with different malignancy and aggressiveness: BHLHE40, FOXP1, LOC285205, ITGA9, CTDSPL, FGF12, LOC440944/SETD5, VHL, CLCN2, OSBPL10/ZNF860, LMCD1, FAM19A4, CAND2, MAP4, KY, and LRRC58. Moreover, we probabilistically estimated putative functional relations between the genes within each set using the network enrichment analysis.


Disparities in mammography use among US women aged 40-64 years, by race, ethnicity, income, and health insurance status, 1993 and 2005.
To examine current disparities in mammography use, and changes in disparities over time by race, ethnicity, income, insurance, and combinations of these characteristics. Comparison of cross-sectional surveys of mammography use using the 1993 and 2005 National Health Interview Survey. Women aged 40-64 (1993, n = 4167; 2005, n = 7434). Mammogram within prior 2 years. In 2005, uninsured women reported the lowest mammography use (38.3%). Though screening increased 6.9 percentage points among low-income, uninsured women, the overall disparity between insured and uninsured women did not change significantly between 1993 and 2005. Screening seems to have declined among middle-income, uninsured women, increasing the gap compared with middle-income, insured women. The lower mammography use in 1993 among American Indian/Alaska Native compared with white women was not present in 2005; however, lower use among Asian compared with white women emerged in 2005. We found no differences between African American and white women. Hispanic women were less likely than non-Hispanic women to report screening in 2005 (58.1% vs. 69.0%). Although mammography use increased for some groups between 1993 and 2005, low-income, uninsured women continued to have the lowest screening rates in 2005 and the disparity for this group was not reduced. The gap in screening use for middle-income, uninsured women increased, resulting from possible declines in mammography even for uninsured women not in poverty. Asian women became less likely to receive screening in 2005. Continuing efforts are needed to eliminate disparities. Increased efforts are especially needed to address the large persistent disparity for uninsured women, including middle-income uninsured women.


History of Cardiothoracic Surgery at Columbia University: A Century at the Vanguard of Clinical Care, Education, and Innovation.
The Columbia University Cardiothoracic Surgery Program dates back to the earliest days of the specialty itself, when the first pioneers ventured into the chest, and eventually the heart, to treat diseases previously believed to be beyond the reach of medicine. This spirit of innovation, creativity, and vision has grown over the ensuing century and has driven the development of advances that have defined the specialty and saved countless lives. From novel techniques for the repair of complex congenital cardiac defects and acquired cardiovascular diseases, to comprehensive management of lung and esophageal maladies, and to the marvel of minimally invasive and percutaneous interventions, the march of progress has never been stronger, more dramatic, or more consequential that it is at Columbia today. Fueled by people who -- as descendants of those early pioneers -- have been raised in the "Columbia culture," the commitment to innovation and education has never been greater.


Ginsenoside Rg3 inhibits the migration and invasion of liver cancer cells by increasing the protein expression of ARHGAP9.
Ginsenoside Rg3, a naturally occurring phytochemical, serves an important role in the prevention and treatment of cancer. In the present study, with the aim to reveal the molecular mechanism of Rg3 in liver cancer cell metastasis, the anti-migration and anti-invasion effects of Rg3 on liver cancer cells were investigated. It was demonstrated that Rg3 caused marked inhibition of cell migration and invasion of human liver cancer cells, HepG2 and MHCC-97L, in vitro, and the growth of HepG2 and MHCC-97L tumors in BABL/c nude mice. The protein expression of Rho GTPase activating protein 9 (ARHGAP9) was increased both in HepG2 and MHCC-97L cells. Following ARHGAP9 knockdown, the results of Transwell and tumorigenesis assays revealed that the anti-migration, anti-invasion and anti-tumor growth effects of Rg3 were impaired significantly. The increased expression of ARHGAP9 protein induced by Rg3 was remarkably suppressed. All results suggested that ARHGAP9 protein may be a vital regulator in the anti-metastatic role of Rg3. To the best of our knowledge, the present study is the first to report that Rg3 effectively suppressed the migration and invasion of liver cancer cells by upregulating the protein expression of ARHGAP9, indicating a novel natural therapeutic agent and a therapeutic target for the treatment of liver cancer.


The importance of loading frequency, rate and vibration for enhancing bone adaptation and implant osseointegration.
Mechanical loading is one of the key factors that influence bone mass and the osseointegration of bone-anchored implants. From a clinical point of view, mechanical stimulation may be used to enhance bone strength and implant osseointegration. Among the many loading parameters that influence the response to mechanical loading, the effects of loading frequency and rate have been investigated in many studies. In this paper the most relevant animal studies that have addressed the effect of loading frequency, rate, and vibration on either bone adaptation or implant osseointegration are systematically reviewed. Apparently contradictory results are discussed and interpreted within the context of mechanotransduction and mechanoregulation of bone. A combined experimental and computational approach is suggested to address some of the remaining research questions.


Overproduction of antiplatelet antibody against glycoprotein IIb after splenectomy in a patient with Evans syndrome resulting in acquired thrombasthenia.
We treated a 33-year-old female with Evans syndrome. She received high dose gamma globulin, prednisolone, and azathioprine, and her platelet count transiently increased. After splenectomy, the platelet count markedly increased. However, the bleeding tendency worsened and the bleeding time was prolonged. A platelet defect, characteristic of thrombasthenia, was found. Antigen-captured ELISA and Western blotting revealed that the patient's serum had an IgG autoantibody against platelet membrane glycoprotein IIb and the patient's plasma inhibited normal platelet aggregation. These findings suggest that overproduction of the antiplatelet antibody is triggered by platelet recovery due to splenectomy and affects platelet function resulting in acquired thrombasthenia.


Ring-opening homo- and co-polymerization of lactides and ε-caprolactone by salalen aluminum complexes.
Aluminum complexes of non-chiral-salalen ligands were investigated in the catalysis of ring-opening polymerization (ROP) of lactide and ε-caprolactone and in their copolymerization. The aluminum-salalen complexes were found to polymerize all varieties of lactide, namely: l-, d-, rac- and meso-lactide, and showed moderate productivities. rac-LA gave rise to isotactic polylactides (with Pm up to 72%), while meso-LA gave rise to heterotactic polylactides (with a Pm of 79%). An experiment was designed for distinguishing between chain-end control and enantiomorphic-site control combined with polymeryl exchange for the isotactic stereoblock microstructure observed for the PLA produced from rac-LA; it gave strong evidence for polymeryl exchange between propagating species. Finally, this class of catalysts promoted the copolymerization of ε-caprolactone and lactides. In particular, compound allowed controlled random copolymerization of ε-caprolactone and l-lactide.


Done good.
How did bioethics manage to grow, flourish and ultimately do so well from a very unpromising birth in the 1970s? Many explanations have been advanced. Some ascribe the field's growth to a puzzling, voluntary abnegation of moral authority by medicine to non-physicians. Some think bioethics survived by selling out to the biomedical establishment-public and private. This transaction involved bestowing moral approbation on all manner of biomedicine's doings for a seat at a well-stocked funding table. Some see a sort of clever intellectual bamboozlement at work wherein bioethicists pitched a moral elixir of objective expertise that the morally needy but unsophisticated in medicine and the biological sciences were eager to swallow. While each of these reasons has its defenders, I think the main reason that bioethics did well was that it did good. By using the media to move into the public arena, the field engaged the public imagination, provoked dialogue and debate, and contributed to policy changes that benefitted patients and healthcare providers.


Human Cochlear Histopathology Reflects Clinical Signatures of Primary Neural Degeneration.
Auditory neuropathy is a significant and understudied cause of human hearing loss, diagnosed in patients who demonstrate abnormal function of the cochlear nerve despite typical function of sensory cells. Because the human inner ear cannot be visualized during life, histopathological analysis of autopsy specimens is critical to understanding the cellular mechanisms underlying this pathology. Here we present statistical models of severe primary neuronal degeneration and its relationship to pure tone audiometric thresholds and word recognition scores in comparison to age-matched control patients, spanning every decade of life. Analysis of 30 ears from 23 patients shows that severe neuronal loss correlates with elevated audiometric thresholds and poor word recognition. For each ten percent increase in total neuronal loss, average thresholds across patients at each audiometric test frequency increase by 6.0 dB hearing level (HL). As neuronal loss increases, threshold elevation proceeds more rapidly in low audiometric test frequencies than in high frequencies. Pure tone average closely agrees with word recognition scores in the case of severe neural pathology. Histopathologic study of the human inner ear continues to emphasize the need for non- or minimally invasive clinical tools capable of establishing cellular-level diagnoses.


Validation of prospective portion size and latency to eat as measures of reactivity to snack foods.
In experimental studies that investigate reactivity to the sight and smell of highly palatable snack foods, ad libitum food intake is commonly used as a behavioural outcome measure. However, this measure has several drawbacks. The current study investigated two intake-related measures not yet validated for food cue exposure research involving common snack foods: prospective portion size and latency to eat. We aimed to validate these measures by assessing prospective portion size and eating latencies in female undergraduate students who either underwent snack food exposure or a control exposure. Furthermore, we correlated prospective portion size and latency to eat with commonly used measures of food cue reactivity, i.e., self-reported desire to eat, salivation, and ad libitum food intake. Results showed increases in prospective portion size after food cue exposure but not after control exposure. Latency to eat did not differ between the two conditions. Prospective portion size correlated positively with desire to eat and food intake, and negatively with latency to eat. Latency to eat was also negatively correlated with desire to eat and food intake. It is concluded that the current study provides initial evidence for the prospective portion size task as a valid measure of reactivity to snack foods in a Dutch female and mostly healthy weight student population.


Characterization of BiP Genes from Pepper (Capsicum annuum L.) and the Role of CaBiP1 in Response to Endoplasmic Reticulum and Multiple Abiotic Stresses.
Adverse environmental conditions have a detrimental impact on crop growth and development, and cause protein denaturation or misfolding. The binding protein (BiP) plays an important protective role by alleviating endoplasmic reticulum (ER) stress induced by misfolded proteins. In this study, we characterized three BiP genes (CaBiP1, CaBiP2, and CaBiP3) in pepper, an economically important vegetable and spice species. The role of CaBiP1 in plant tolerance to ER stress and adverse environmental conditions (including heat, salinity, osmotic and drought stress) were investigated. All the expected functional and signaling domains were detected in three BiP proteins, but the motifs and exon-intron distribution differed slightly in CaBiP3. CaBiP1 and CaBiP2 were constitutively expressed in all the tested tissues under both normal and stressed conditions, whereas CaBiP3 was mainly expressed following stress. Silencing of CaBiP1 reduced pepper tolerance to ER stress and various environment stresses, and was accompanied by increased H2O2 accumulation, MDA content, relative electric leakage (REL), water loss rate, and a reduction in soluble protein content and relative water content (RWC) in the leaves. Conversely, overexpression of CaBiP1 in Arabidopsis enhanced tolerance to ER stress and multiple environment stresses, as demonstrated by an increase in germination rate, root length, survival rate, RWC, the unfolded protein response (UPR) pathway, and a decrease in water loss rate. Our results suggest that CaBiP1 may contribute to plant tolerance to abiotic stresses by reducing ROS accumulation, increasing the water-retention ability, and stimulating UPR pathways and expression of stress-related genes.


Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan.
The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of doses remain uncertain. In this study, we examined the long-term cellular and humoral immune responses following the fifth administration of the mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis. To our knowledge, this is the first study to monitor long-term data on humoral and cellular immunity dynamics in high-risk populations after five doses of mRNA vaccination, including the bivalent mRNA vaccine. Whereas most patients maintained humoral immunity throughout the observation period, we observed reduced cellular immune reactivity as measured by the ancestral-strain-stimulated ELISpot assay in a subset of patients. Half of the individuals (50%; 14/28) maintained cellular immunity three months after the fifth dose, despite acquiring humoral immunity. The absence of a relationship between positive controls and T-Spot reactivity suggests that these immune alterations were specific to SARS-CoV-2. In multivariable analysis, participants aged ≥70 years showed a marginally significant lower likelihood of having reactive results. Notably, among the 14 individuals who received heterologous vaccines, 13 successfully acquired cellular immunity, supporting the effectiveness of this administration strategy. These findings provide valuable insights for future vaccination strategies in vulnerable populations. However, further research is needed to evaluate the involvement of immune tolerance and exhaustion through repeated vaccination to optimize immunization strategies.


A novel kinin-generating protease (kininogenase) in the porcine anterior pituitary.
The purpose of the present study was to determine whether porcine pituitary tissue contains kininogenase activity. Porcine anterior and posterior pituitaries were homogenized in 0.25 M sucrose containing 10 mM Tris/HCl (pH 7.5) and the homogenate subjected to differential centrifugation (10,000 x g for 20 min, then 105,000 x g for 60 min). Fractions were examined for kininogenase activity using canine plasma kininogen as the substrate; kinins were measured by bioassay or radioimmunoassay. The anterior pituitary was found to have kininogenase activity highly concentrated in the 105,000 x g particulate pellet (376 ng of bradykinin generated/mg of protein/h) with little or no activity detectable in other fractions. The porcine posterior pituitary 105,000 x g pellet contained 22% of the kininogenase activity of the anterior pituitary. Anterior pituitary kininogenase activity had a broad pH optimum (pH 7.5-9.0), was heat-sensitive, was inhibited by dithiothreitol, soybean trypsin inhibitor, aprotinin, and diisopropyl fluorophosphate, and was resistant to lima bean trypsin inhibitor, pepstatin, and hirudin. Bradykinin was found to be the principal kinin generated by the anterior pituitary kininogenase as determined by high performance liquid chromatography. The anterior pituitary kininogenase differed from other kininogenases in its sensitivity to inhibitors and substrate specificity.


[Study on fabrication of controllable microchannel structure scaffolds and rotating dynamic culture].
It is the critical technology for bone tissue engineering to fabricate scaffolds, especially to fabricate the internal microchannel of scaffolds. Utilizing stereolithography rapid prototyping indirect fabrication approach, suitable size microchannel structure scaffolds with orientation, branching, and interconnectivity under control was manufactured. Observation under light microscope showed that the arrange of microchannel size was 200-600 microm, the orientation and branching were accorded with designed structure, and all the microchannels were completely interconnected. Scaffolds seeded with osteoblast cells were put into 6-well plate and rotating 3D dynamic culture system which was developed in our lab. The morphology of osteoblasts and the development on the surface and internal microchannel of scaffolds were observed under scanning electron microscope (SEM). The results indicated that the dynamic culture permited an even distribution of cells across the surface of scaffolds, besides, a few cells grew into the lumen of microchannels.


Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling.
Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis.


[Comparison and improvement in the methods of establishing animals model of experimental chronic sinusitis in rabbits].
To compare and improve the methods of establishing animal model of experimental chronic sinusitis in rabbits . Sixty-six New Zealand white rabbits were divided into seven groups: control group, sham-operation group I, sham-operation group II, bacteria inoculation group, ostia-blocked group, ostia-blocked and bacteria inoculation group, incomplete ostium blocked and set-cotton group. The animals were examined by the methods of histology and bacteriology after 42 days. The positive rate of chronic inflammation in ostium blocked group was 80%, inoculated staphylococcus group was 100%, incomplete ostium blocked and set-cotton group was 100%, and the other groups were 0%. All infected sinuses displayed signs of moderate or severe chronic inflammation. The cultivated bacteria were mainly opportunistic pathogens. The probability of having abscess in maxillary sinus was high in ostia-blocked and bacteria inoculation group. The method of incomplete ostium blockage and set cotton can establish stable chronic sinusitis model, it is a simple and perfect method.


Developing a dynamic simulation model to support the nationwide implementation of whole genome sequencing in lung cancer.
This study shows how dynamic simulation modeling can be applied in the context of the nationwide implementation of Whole Genome Sequencing (WGS) for non-small cell lung cancer (NSCLC) to inform organizational decisions regarding the use of complex and disruptive health technologies and how these decisions affect their potential value. Using the case of the nationwide implementation of WGS into clinical practice in lung cancer in the Dutch healthcare system, we developed a simulation model to show that including service delivery features across the diagnostic pathway can provide essential insight into the affordability and accessibility of care at the systems level. The model was implemented as a hybrid Agent-Based Model and Discrete-Event Simulation model in AnyLogic and included 78 hospital agents, 7 molecular tumor board agents, 1 WGS facility agent, and 5313 patient agents each year in simulation time. The model included patient and provider heterogeneity, including referral patterns, capacity constraints, and diagnostic workflows. Patient preference and adoption by healthcare professionals were also modeled. The model was used to analyze a scenario in which only academic hospitals have implemented WGS. To prevent delays in the diagnostic pathway, the capacity to sequence at least 1600 biopsies yearly should be present. There is a two-fold increase in mean diagnostic pathway duration between no patients referred or all patients referred for further diagnostics. The systems model can complement conventional health economic evaluations to investigate how the organization of the workflow can influence the actual use and impact of WGS. Insufficient capacity to provide WGS and referral patterns can substantially impact the duration of the diagnostic pathway and thus should be considered in the implementation of WGS.


Total fatty acid composition of duck fatty tissues.
Total lipids extracted from duck fatty tissues were fractionated on thin layer plates into polar lipids and neutral lipids. Neutral lipids were similarly fractionated into their components. Fatty acid methyl esters from total lipids were fractionated by gas-liquid-chromatography. Results indicated that duck fatty tissues are mostly formed by neutral lipids and that triglycerides comprise the vast majority of neutral lipids. Results also indicated that the major fatty acids in duck lipids are: oleic greater than linoleic greater than stearic greater than palmitoleic. About 73% of all fatty acids present belong to the C-18 series. The unsaturation level for duck lipids is about 73%.


Artificial Intelligence in Digital Pathology to Advance Cancer Immunotherapy.
Immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of many malignancies. For instance, in lung cancer, however, only 20~30% of patients can achieve durable clinical benefits from ICI monotherapy. Histopathologic and molecular features such as histological type, PD-L1 expression, and tumor mutation burden (TMB), play a paramount role in selecting appropriate regimens for cancer treatment in the era of immunotherapy. Unfortunately, none of the existing features are exclusive predictive biomarkers. Thus, there is an imperative need to pinpoint more effective biomarkers to identify patients who may achieve the most benefit from ICIs. The adoption of digital pathology in clinical flow, as being powered by artificial intelligence (AI) especially deep learning, has catalyzed the automated analysis of tissue slides. With the breakthrough of multiplex bioimaging technology, researchers can comprehensively characterize the tumor microenvironment, including the different immune cells' distribution, function, and interaction. Here, we briefly summarize recent AI studies in digital pathology and share our perspective on emerging paradigms and directions to advance the development of immunotherapy biomarkers.


Learning of the conditioned eye-blink response is impaired by an antisense insulin-like growth factor I oligonucleotide.
The cerebellum is thought to be critically involved in learning and retention of several types of classically conditioned motor responses. We investigated whether insulin-like growth factor I (IGF-I) may constitute an intercellular mediator of a motor learning task because previous findings indicated that IGF-I from the inferior olive modulates glutamate-induced gamma-aminobutyric acid release by Purkinje cells in the cerebellar cortex. Synaptic plasticity of the Purkinje cell is thought to be instrumental in motor learning. We found that injection of an IGF-I antisense oligonucleotide in the inferior olive elicited a complete inhibition of conditioned eye-blink learning in freely moving rats. This blockage was reversible and recovered when the levels of cerebellar IGF-I returned to normal values. Injection of a sense oligonucleotide did not interfere with the acquisition of the conditioned response. On the other hand, retention of the conditioned response was not impaired by subsequent injection of the IGF-I antisense oligonucleotide, indicating that olivocerebellar IGF-I is essential for the acquisition of the conditioned eye-blink response but is not essential for its retention.