Chemical Structure Diversity and Extensive Biological Functions of Specialized Metabolites in Rice.
Rice (Oryza sativa L.) is thought to have been domesticated many times independently in China and India, and many modern cultivars are available. All rice tissues are rich in specialized metabolites (SPMs). To date, a total of 181 terpenoids, 199 phenolics, 41 alkaloids, and 26 other types of compounds have been detected in rice. Some volatile sesquiterpenoids released by rice are known to attract the natural enemies of rice herbivores, and play an indirect role in defense. Momilactone, phytocassane, and oryzalic acid are the most common diterpenoids found in rice, and are found at all growth stages. Indolamides, including serotonin, tryptamine, and N-benzoylserotonin, are the main rice alkaloids. The SPMs mainly exhibit defense functions with direct roles in resisting herbivory and pathogenic infections. In addition, phenolics are also important in indirect defense, and enhance wax deposition in leaves and promote the lignification of stems. Meanwhile, rice SPMs also have allelopathic effects and are crucial in the regulation of the relationships between different plants or between plants and microorganisms. In this study, we reviewed the various structures and functions of rice SPMs. This paper will provide useful information and methodological resources to inform the improvement of rice resistance and the promotion of the rice industry.


Peripheral Lipopolyssacharide Rapidly Silences REM-Active LHGABA Neurons.
Immune factors (e.g., cytokines, chemokines) can alter the activity of neuronal circuits to promote "sickness behavior," a suite of adaptive actions that organisms exhibit in response to infection/injury in order to maximize their chances of recovery (i.e., return to homeostasis). This includes drastic alterations in sleep/wake states, locomotor activity, and food intake, among other behaviors. Despite the ample evidence highlighting interactions between the brain and systemic immunity, studies on how immune challenges alter the activity of genetically defined cell populations controlling arousal states are scarce. As the lateral hypothalamus (LH) serves a major integrative function in behavioral arousal, food intake, and monitoring and responding to changes in systemic physiology, we investigated how GABAergic neurons within this brain region alter their activity across normal sleep/wake states and in response to a peripheral immune challenge with bacterial endotoxin [lipopolysaccharides (LPS)]. Using fiber photometry (GCaMP6s Ca2+ signal) in tandem with electroencephalogram (EEG)/EMG recordings to determine arousal states, we observed that population activity of GABAergic neurons in the lateral hypothalamus (LHGABA) is highest during rapid-eye-movement sleep (REM), and this activity changes drastically across spontaneous arousal state transitions, with the lowest activity observed during non-REM sleep. Upon intraperitoneal LPS challenge, LHGABA neurons rapidly decrease their activity in tandem with elimination of REM sleep behavior (characteristic of cytokine-induced sickness). Together, these data suggest that peripheral immune challenges can rapidly (in < 40 min) alter subcortical neuronal circuits controlling arousal states. Additionally, we demonstrate that fiber photometry offers a sensitive and cell-type specific tool that can be applied to study the neuronal substrates of sickness behavior.


RAB-6.1 and RAB-6.2 Promote Retrograde Transport in C. elegans.
Retrograde transport is a critical mechanism for recycling certain membrane cargo. Following endocytosis from the plasma membrane, retrograde cargo is moved from early endosomes to Golgi followed by transport (recycling) back to the plasma membrane. The complete molecular and cellular mechanisms of retrograde transport remain unclear. The small GTPase RAB-6.2 mediates the retrograde recycling of the AMPA-type glutamate receptor (AMPAR) subunit GLR-1 in C. elegans neurons. Here we show that RAB-6.2 and a close paralog, RAB-6.1, together regulate retrograde transport in both neurons and non-neuronal tissue. Mutants for rab-6.1 or rab-6.2 fail to recycle GLR-1 receptors, resulting in GLR-1 turnover and behavioral defects indicative of diminished GLR-1 function. Loss of both rab-6.1 and rab-6.2 results in an additive effect on GLR-1 retrograde recycling, indicating that these two C. elegans Rab6 isoforms have overlapping functions. MIG-14 (Wntless) protein, which undergoes retrograde recycling, undergoes a similar degradation in intestinal epithelia in both rab-6.1 and rab-6.2 mutants, suggesting a broader role for these proteins in retrograde transport. Surprisingly, MIG-14 is localized to separate, spatially segregated endosomal compartments in rab-6.1 mutants compared to rab-6.2 mutants. Our results indicate that RAB-6.1 and RAB-6.2 have partially redundant functions in overall retrograde transport, but also have their own unique cellular- and subcellular functions.


Replication of Relevant SNPs Associated with Cardiovascular Disease Susceptibility Obtained from GWAs in a Case-Control Study in a Canarian Population.
Recent genome-wide single nucleotide polymorphism (SNP) association studies (GWAS) have identified a number of SNPs that were significantly associated with coronary artery disease (CAD) and myocardial infarction (MI). We tested for replication of the previously described association with CAD in our case-control datasets of SNPs variants located at 1p13.1, 2q33.1, 10q11.1, 9p21, and 21q22. We observed a small significant risk associated of the SNP rs10757274 with CAD in the PROCAGENE study. Besides, the multilocus combination rs10757274 and rs1333048 gave a near significant result. We confirmed that the SNP rs10757274 showed association with CAD in the PROCAGENE study, although after applying the Bonferroni correction was not longer significant. Independent replication studies in other populations are needed to unequivocally confirm the association.


Flow cytometric determination of ploidy in prostatic adenocarcinoma: a comparison with seminal vesicle involvement and histopathological grading as a predictor of clinical recurrence.
Flow cytometry was used to evaluate 88 deparaffinized radical prostatectomy specimens to compare deoxyribonucleic acid ploidy in prostatic adenocarcinoma as a predictor of disease progression with other well documented predictors of clinical recurrence. Aneuploidy, Gleason grade and seminal vesicle involvement were nonindependent variables, and all correlated to statistical significance with disease recurrence. The incidence of aneuploidy in the total population was 51 of 88 (58 per cent). Aneuploidy was found in 25 of 28 primary tumors (89 per cent) from patients who subsequently had recurrent disease. Aneuploidy was noted in 40 of 59 specimens (68 per cent) exhibiting seminal vesicle involvement, compared to 11 of 29 (38 per cent) without seminal vesicle involvement (p less than 0.01). The probability of an interval free of disease of 60 months was calculated by Kaplan-Meier analysis to be 85 per cent in diploid specimens compared to 9 per cent in aneuploid specimens (p less than 0.001), and 87 per cent in the absence of seminal vesicle involvement compared to 28 per cent in the presence of seminal vesicle involvement (p less than 0.003). The probability of remaining free of disease in patients exhibiting concomitant diploidy and seminal vesicle involvement (17) was 73 per cent compared to 8 per cent in those with aneuploid specimens and seminal vesicle involvement (p less than 0.004). The incidence of recurrence in patients with Gleason sums of 7 or less was 22 per cent compared to 62 per cent in patients with Gleason sums of greater than 7. There was a 29 per cent incidence of recurrence in intermediate grade tumors (Gleason sum 5 to 7) but only 5 per cent of the patients with intermediate grade diploid tumors had recurrent disease. In conclusion, the recognition of a deoxyribonucleic acid aneuploid stem line in a primary prostatic adenocarcinoma is correlated statistically with a greater likelihood of seminal vesicle invasion and subsequent development of recurrent disease. The markedly increased probability of remaining free of disease in diploid patients, even in the presence of seminal vesicle involvement, suggests that routine flow cytometric analysis in prostatic adenocarcinoma would significantly enhance prognostic stratification.


[Guideline 'Chronic heart failure'].
A new Dutch clinical practice guideline has been developed for the diagnosis, treatment and supportive care of patients with chronic heart failure. This has been formulated by a multidisciplinary working group, set up by the Netherlands Heart Foundation and the Netherlands Society of Cardiology, in cooperation with the Dutch Institute for Healthcare Improvement. Heart failure is defined as: 'a complex of complaints and symptoms resulting from an inadequate pumping function of the heart'. Indications for heart failure are dyspnoea on exertion, reduced exertion tolerance and oedema. By using data from the medical history, case history, physical examination and simple additional tests (laboratory tests, ECG, chest X-ray photos) it is possible to demonstrate or exclude heart failure in clear-cut cases. Doppler ultrasonography should be performed in all patients where heart failure is suspected but cannot be clearly demonstrated. The initial treatment for patients with heart failure with reduced systolic LV function generally consists of the administration of a thiazide or loop diuretic together with an angiotensin-converting enzyme inhibitor and a beta-blocker, to which digoxin and/or spironolactone may be added. For very old patients extra attention should be given to the comorbidity and the medication and dosing scheme should be as simple as possible. The worse the cardiac function, the more the salt and fluid intake should be limited and the more strictly the weight should be monitored.


Oxidative stress by the mitochondrial monoamine oxidase B mediates calcium pyrophosphate crystal-induced arthritis.
Calcium pyrophosphate (CPP) crystal deposition in the joints is associated with a heterogeneous set of debilitating syndromes characterized by inflammation and pain, for which no effective therapies are currently available. As we found that the mitochondrial enzyme monoamine oxidase B (MAO-B) plays a fundamental role in promoting inflammatory pathways, this study aims at assessing the efficacy of two clinical-grade inhibitors (iMAO-Bs) in preclinical models of this disease, to pave the way for a novel treatment. We tested our hypothesis in two murine models of CPP-induced arthritis, by measuring cytokine and chemokine levels, along with immune cell recruitment. iMAO-Bs (rasagiline and safinamide) were administered either before or after crystal injection. To elucidate the molecular mechanism, we challenged in vitro primed macrophages with CPP crystals and assessed the impact of iMAO-Bs in dampening proinflammatory cytokines and in preserving mitochondrial function. Both in preventive and therapeutic in vivo protocols, iMAO-Bs blunted the release of proinflammatory cytokines (interleukin (IL)-6 and IL1-β) and chemokines (CXCL10, CXCL1, CCL2 and CCL5) (n>6 mice/group). Importantly, they also significantly reduced ankle swelling (50.3% vs 17.1% [P<0.001] and 23.1% [P=0.005] for rasagiline and safinamide, respectively). Mechanistically, iMAO-Bs dampened the burst of reactive oxygen species (ROS) and the mitochondrial dysfunction triggered by CPP crystals in isolated macrophages. Moreover, iMAO-Bs blunted cytokine secretion and NLRP3 inflammasome activation through inhibition of the NF-κB and STAT3 pathways. iMAO-Bs dampen inflammation in murine models of crystal-induced arthropathy, thereby uncovering MAO-B as a promising target to treat these diseases.


Using phylogenetics to detect pollinator-mediated floral evolution.
The development of comparative phylogenetic methods has provided a powerful toolkit for addressing adaptive hypotheses, and researchers have begun to apply these methods to test the role of pollinators in floral evolution and diversification. One approach is to reconstruct the history of both floral traits and pollination systems to determine if floral trait change is spurred by shifts in pollinators. Looking across multiple shifts, it is also possible to test for significant correlations between floral evolution and pollinators using parsimony, likelihood and Bayesian methods for discrete characters or using statistical comparative methods for continuous characters. Evolutionary shifts in pollinators and floral traits may cause changes in diversification rates, and new methods are available for simultaneously studying character evolution and diversification rates. Relatively few studies have yet used formal comparative methods to elucidate how pollinators affect floral evolution across the phylogeny, and fruitful directions for future applications are discussed.


Designing Thin, Ultrastretchable Electronics with Stacked Circuits and Elastomeric Encapsulation Materials.
Many recently developed soft, skin-like electronics with high performance circuits and low modulus encapsulation materials can accommodate large bending, stretching, and twisting deformations. Their compliant mechanics also allows for intimate, nonintrusive integration to the curvilinear surfaces of soft biological tissues. By introducing a stacked circuit construct, the functional density of these systems can be greatly improved, yet their desirable mechanics may be compromised due to the increased overall thickness. To address this issue, the results presented here establish design guidelines for optimizing the deformable properties of stretchable electronics with stacked circuit layers. The effects of three contributing factors (i.e., the silicone inter-layer, the composite encapsulation, and the deformable interconnects) on the stretchability of a multilayer system are explored in detail via combined experimental observation, finite element modeling, and theoretical analysis. Finally, an electronic module with optimized design is demonstrated. This highly deformable system can be repetitively folded, twisted, or stretched without observable influences to its electrical functionality. The ultrasoft, thin nature of the module makes it suitable for conformal biointegration.


The role of central and peripheral vision in expert decision making.
The purpose of this study was to investigate the role of central and peripheral vision in expert decision making. A gaze-contingent display was used to selectively present information to the central and peripheral areas of the visual field while participants performed a decision-making task. Eleven skilled and eleven less-skilled male basketball players watched video clips of basketball scenarios in three different viewing conditions: full-image control, moving window (central vision only), and moving mask (peripheral vision only). At the conclusion of each clip participants were required to decide whether it was more appropriate for the ball-carrier to pass the ball or to drive to the basket. The skilled players showed significantly higher response accuracy and faster response times compared with their lesser-skilled counterparts in all three viewing conditions, demonstrating superiority in information extraction that held irrespective of whether they were using central or peripheral vision. The gaze behaviour of the skilled players was less influenced by the gaze-contingent manipulations, suggesting they were better able to use the remaining information to sustain their normal gaze behaviour. The superior capacity of experts to interpret dynamic visual information is evident regardless of whether the visual information is presented across the whole visual field or selectively to either central or peripheral vision alone.


A new case of holoprosencephaly-polydactyly syndrome with alobar holoprosencephaly, preaxial polydactyly and congenital glaucoma.
We report a case of a female baby born at 34 weeks of gestation. Birth weight was 1760 g (10th-25th centile), length 41cm (10th-25th centile) and head circumference 27cm (< 10th centile). Clinical examination revealed microcephaly, hypotelorism, micrognathia, a flat rudimentary nose, high palate, thick dysplastic low-set ears, a short neck, preaxial polydactyly of the right hand, and overriding toes. Investigations showed bilateral congenital glaucoma, alobar holoprosencephaly, severe ventriculomegaly and absence midline structures of the brain, a large atrial septal defect. The karyotype was 46,XX. The case was also diagnosed as having holoprosencephaly-polydactyly syndrome (pseudotrisomy 13) because she had alobar holoprosencephaly, preaxial polydactyly, facial dysmorfism (hypotelorism, micrognathia, a flat rudimentary nose, high palate, thick dysplastic low-set ears) and normal karyotype.


European ancestry and resting metabolic rate in older African Americans.
Resting metabolic rate (RMR) contributes 60-80% of total energy expenditure and is consistently lower in populations of African descent compared with populations of European populations. Determination of European ancestry (EA) through single nucleotide polymorphism (SNP) analysis would provide an initial step for identifying genetic associations that contribute to low RMR. We sought to evaluate the association between RMR and EA in African Americans. RMR was measured by indirect calorimetry in 141 African American men and women (aged 74.7±3.0 years) enrolled in a substudy of the Health, Aging and Body Composition Study. Ancestry informative markers were used to estimate individual percent EA. Multivariate regression was used to assess the association between RMR and EA after adjustments for soft tissue fat-free mass (STFFM), fat mass, age, study site, physical activity level and sex. Mean EA was 23.8±16% (range: 0.1-70.7%) and there were no differences by sex. Following adjustments, each percent EA was associated with a 1.6 kcal/day (95% Confidence interval: 0.42, 2.7 kcal/day) higher RMR (P=0.008). This equates to a 160 kcal/day lower RMR in a population of completely African ancestry, with one of completely European ancestry. Additional adjustment for trunk STFFM that partially accounts for high-metabolic rate organs did not affect this association. EA in African Americans is strongly associated with higher RMR. The data suggest that population differences in RMR may be due to genetic variants.


Post-imprinting modification based on multilevel mesoporous silica for highly sensitive molecularly imprinted fluorescent sensors.
When molecularly imprinted fluorescent polymers (MIFPs) are prepared by the doping method (d-MIFPs), the fluorescent nanoparticles are quenched and passivated during the polymerization and elution process, and their detection sensitivity would be reduced. In this study, to overcome this drawback, MIFPs were synthesized by post-imprinting modification based on multilevel mesoporous structured silica. Briefly, multilevel mesoporous-structured BPA-imprinted polymers (MIPs) were prepared at first, and then, CdTe quantum dots were anchored onto the large pores of the MIPs to form p-MIFPs. Due to the well-maintained fluorescence intensity and low background, the sensitivity of the p-MIFPs was two orders of magnitude higher than that of the d-MIFPs. The F0/F- 1 of p-MIFPs was linear with BPA in the range of 0.005 to 4.0 μM with an LOD of 0.57 nM. Furthermore, post-imprinting modification was adopted to achieve ratiometric fluorescent MIPs (p-r-MIFPs) by simultaneously anchoring carbon dots and quantum dots onto the MIPs. The p-MIFPs and p-r-MIFPs were successfully applied to determine BPA in water samples with average recoveries ranging from 96.4% to 102.0% and an RSD below 4.1%. The results prove that post-imprinting modification is an effective method to construct MIFPs with conspicuous sensitivity, and multilevel mesoporous silica is an ideal matrix for the post-imprinting modification.


Novel dermaseptins from Phyllomedusa hypochondrialis (Amphibia).
Six new antimicrobial peptides structurally related to the dermaseptin family have been isolated from the skin secretion of the amphibian Phyllomedusa hypochondrialis. The primary structures of these molecules named as DShypo 01, 02, 03, 04, 06, and 07 were determined by de novo MS/MS experiments, Edman degradation, and cDNA sequencing. The fifth peptide was found to be precisely the same DS 01 from Phyllomedusa oreades previously described by our group. The majority of the peptides purified from the crude skin secretion could be directly localized and mapped onto a freshly dissected dorsal skin fragment using mass spectrometry-imaging techniques. Comparisons between peptides and commercial drugs on their antibacterial and anti-Leishmania amazonensis efficiencies, associated with peptide lytic effects on mammalian blood cells and surface plasmon resonance interaction studies on immobilized DMPC vesicles, were also performed.


Ongoing clinical trials of the pleiotropic effects of statins.
The multiple effects (ie, pleiotropic effects of statins) have received increasing recognition and may have clinical applicability across a broad range of cardiovascular and noncardiovascular conditions. To determine the relevance and significance of ongoing clinical trials of the pleiotropic effects of statins, focusing on nonlipid effects. Ongoing trials were identified through personal communication, reports presented at scientific meetings (2000-2004), and queries made to AstraZeneca, Bristol-Myers Squibb Co, Merck & Co, Novartis, and Pfizer, manufacturers of the currently marketed statins. Published trials and other source material were identified through electronic searches on MEDLINE (1990-2003), abstract books, and references identified from bibliographies of pertinent articles. Eligible studies were the clinical trials of statins currently under way in which primary or secondary outcomes included the statins' nonlipid (ie, pleiotropic) effect(s). Data were extracted and trial quality was assessed by the authors. Of the 22 ongoing trials of the nonlipid effects of statins identified, 10 assessed inflammatory markers and plaque stabilization, 4 assessed oxidized low density lipoprotein/vascular oxidant stress, 3 assessed end-stage renal disease, 3 assessed fibrinogen/viscosity, 2 assessed endothelial function, 2 assessed acute coronary syndrome, 2 assessed aortic stenosis progression, and 1 each assessed hypertension, osteoporosis, ischemic burden, Alzheimer's disease, multiple sclerosis, and stroke (outcomes often overlapped). Given the excellent safety and tolerability of statins as a class, full exploration of their pleiotropic effects has the potential to provide additional benefits to many patients.


A Multi-Class Proportional Myocontrol Algorithm for Upper Limb Prosthesis Control: Validation in Real-Life Scenarios on Amputees.
Functional replacement of upper limbs by means of dexterous prosthetic devices remains a technological challenge. While the mechanical design of prosthetic hands has advanced rapidly, the human-machine interfacing and the control strategies needed for the activation of multiple degrees of freedom are not reliable enough for restoring hand function successfully. Machine learning methods capable of inferring the user intent from EMG signals generated by the activation of the remnant muscles are regarded as a promising solution to this problem. However, the lack of robustness of the current methods impedes their routine clinical application. In this study, we propose a novel algorithm for controlling multiple degrees of freedom sequentially, inherently proportionally and with high robustness, allowing a good level of prosthetic hand function. The control algorithm is based on the spatial linear combinations of amplitude-related EMG signal features. The weighting coefficients in this combination are derived from the optimization criterion of the common spatial patterns filters which allow for maximal discriminability between movements. An important component of the study is the validation of the method which was performed on both able-bodied and amputee subjects who used physical prostheses with customized sockets and performed three standardized functional tests mimicking daily-life activities of varying difficulty. Moreover, the new method was compared in the same conditions with one clinical/industrial and one academic state-of-the-art method. The novel algorithm outperformed significantly the state-of-the-art techniques in both subject groups for tests that required the activation of more than one degree of freedom. Because of the evaluation in real time control on both able-bodied subjects and final users (amputees) wearing physical prostheses, the results obtained allow for the direct extrapolation of the benefits of the proposed method for the end users. In conclusion, the method proposed and validated in real-life use scenarios, allows the practical usability of multifunctional hand prostheses in an intuitive way, with significant advantages with respect to previous systems.


Immunological detection of hCG-like substances in aerobic bacteria of both tumour and non-tumour origin.
Production of hormone-like substances by prokaryotes and unicellular eukaryotes, as well as the presence of a human chorionic gonadotropin-like substance in the serum of individuals with malignancies, have been previously established. To determine the presence and distribution of the production of human chorionic gonadotropin (hCG) among aerobic bacteria, fourteen strains of bacteria of both tumour and non-tumour origin were examined using enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and indirect immunoperoxidase techniques. Of the six bacterial strains tested, half of the tumour-isolates produced an hCG-like substance while non-tumour associated strains of the same species did not do so. Virulent strains of two mycobacterial species also gave high positive values while avirulent Mycobacterium tuberculosis strains (H37Ra) yielded low or negative values. The production of hCG-like substances by mycobacteria, for which no tumour association is known, indicates that tumour association is neither a prerequisite nor a requirement for production of hCG. It appears that the presence of hCG-like substances is a variable character among bacterial species, suggesting that it may have been conserved throughout evolutionary history.


Early experience with multiparametric magnetic resonance imaging-targeted biopsies under visual transrectal ultrasound guidance in patients suspicious for prostate cancer undergoing repeated biopsy.
The purpose of this study was to investigate the detection rate of prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted biopsies (mp-MRI-bx) in patients with prior negative transrectal ultrasound biopsy (TRUS-bx) sessions without previous experience of this. Eighty-three patients with prior negative TRUS-bx scheduled for repeated biopsies due to persistent suspicion of PCa were prospectively enrolled. mp-MRI was performed before biopsy and all lesions were scored according to the Prostate Imaging Reporting and Data System (PI-RADS) and Likert classification. All underwent repeated TRUS-bx (10 cores) and mp-MRI-bx under visual TRUS guidance of any mp-MRI-suspicious lesion not targeted by systematic TRUS-bx. PCa was found in 39 out of 83 patients (47%) and mp-MRI identified at least one lesion with some degree of suspicion in all 39 patients. Both PI-RADS and Likert scoring showed a high correlation between suspicion of malignancy and biopsy results (p < 0.0001). Five patients (13%) had cancer detected only on mp-MRI-bx outside the TRUS-bx areas (p = 0.025) and another seven patients (21%) had an overall Gleason score upgrade of at least one grade based on the mp-MRI-bx. Secondary PCa lesions not visible on mp-MRI were detected by TRUS-bx in six out of 39 PCa patients. The secondary foci were all Gleason 6 (3 + 3) in 5-10% of the biopsy core. According to the Epstein criteria, 37 out of 39 cancer patients were classified as clinically significant. Using mp-MRI, even without previous experience, can improve the detection rate of significant PCa at repeated biopsy and allows more accurate Gleason grading.


Lip morphological changes in orthodontic treatment. Class II division 1: malocclusion and normal occlusion at rest and on smiling.
To evaluate the morphological changes in the lips and to determine the degree of improvement in the smile after orthodontic treatment for Class II division 1 malocclusion. The sample subjects were divided into two groups: a group that consisted of 20 adult female patients with Angle Class II division 1 malocclusion and a control group that consisted of 28 adult female volunteers with normal occlusion. Frontal photographs were taken before and after orthodontic treatment, and 35 landmarks were placed on each tracing made from the photograph. Thereafter, landmarks were digitized into an x- and y-coordinate system with the subnasal point as the origin. The comparisons between pretreatment and posttreatment at rest and on smiling, and the comparisons between Class II division 1 and control group were made using Student's t-test. Both the upper and lower lips in the smile of patients in the Class II division 1 pretreatment group were positioned downward, and the upward movement of the upper lip and mouth corners was smaller in comparison with the control group. These characteristics of the Class II smile improved after orthodontic treatment, but the differences with the control group remained unchanged immediately after treatment. The soft tissue morphology shows a relative improvement after orthodontic treatment.


The ameliorative effect of the Pyracantha fortuneana (Maxim.) H. L. Li extract on intestinal barrier dysfunction through modulating glycolipid digestion and gut microbiota in high fat diet-fed rats.
Pyracantha fortuneana fruits are consumed as a dietary supplement in China and attenuate obesity and metabolic disorders. Obesity is known to be associated with intestinal barrier dysfunction driven by hyperglycemia and gut dysbiosis. However, whether the health benefits of P. fortuneana fruits are linked with the intestinal barrier function (IBF) remains unknown. This study aimed to evaluate the restorative effects of P. fortuneana fruit extract (PFE) on the IBF. Sprague Dawley rats were fed with a chow, a high-fat diet (HFD), or a PFE-supplemented diet for 8 weeks. Results showed that PFE intervention ameliorated HFD-induced intestinal barrier dysfunction by attenuating impaired structural integrity, reducing the elevated lactulose/mannitol ratio, and improving the mRNA and protein expression levels of tight junction proteins in HFD-fed rats. The ameliorations were associated with a beneficial effect on glycolipid homeostasis, as evidenced from the PFE decreasing intestinal absorptive capacity based on the d-xylose excretory rate, lowering the expression of GLUT2 and inhibiting digestive enzyme activities. The proanthocyanidins in the PFE showed greater in vitro inhibition on α-amylase, α-glucosidase, and lipase compared with triterpenoid saponins. Furthermore, the ameliorations on the IBF were also associated with effects on the microbial composition based on 16S rRNA gene sequence analysis. Several bacterial groups, which were linked with gut barrier integrity, were modulated after PFE administration, that is, Actinobacteria, Bacteroidaceae, Corynebacteriaceae, Lactobacillaceae, and S24-7 were elevated and the HFD-induced increase in Clostridia, Ruminococcaceae, Oscillospira, and Flexispira was restored. These data provide evidence for the ameliorative effect of the PFE on diet-induced intestinal barrier functional alternations in association with its capacity to modulate glycolipid digestion and gut microbiota in HFD-fed obese rats.


Influenza is a major contributor to childhood pneumonia in a tropical developing country.
Pneumonia is the leading cause of child mortality worldwide. The role of influenza in childhood pneumonia in tropical developing countries is poorly understood. We undertook population-based surveillance among low-income urban preschool children to determine its role in childhood pneumonia. Longitudinal prospective active surveillance was conducted among randomly selected households in a poor urban area of Dhaka. Nasopharyngeal washes were collected from 1 in 5 children for influenza culture isolation. Clinical data were collected at clinical presentation and through the illness course. From April 1, 2004 through December 31, 2007, 12,062 children presented in clinic with eligible febrile and respiratory illnesses, from whom 321 influenza isolates were obtained from 2370 nasopharyngeal washes (13.5%), representing 16,043 child-years of observation (adjusted influenza incidence 102 episodes/1000 child-years). There were 8198 pneumonia episodes during the period (pneumonia incidence 511 episodes/1000 child-years). Ninety influenza-positive children (28%) developed pneumonia during their illness. Among influenza culture-positive children, those with pneumonia were younger than those without (23.4 vs. 29.7 months, ANOVA: P < 0.001). Pneumonia was more commonly associated with Influenza A (H3N2) than either A (H1N1) or B infections (age-adjusted relative odds (RO) 2.98, [95% CI: 1.56, 5.71] and 2.75, [95% CI: 1.52, 4.98], respectively). Influenza was associated with 10% all childhood pneumonia. Influenza is a major contributor to childhood pneumonia both through high influenza infection incidence and high pneumonia prevalence among infected children. Its contribution to early childhood pneumonia appears under-appreciated in high pneumonia-endemic tropical settings. Influenza vaccine trials against childhood pneumonia are warranted.


Hypertension. Update on use of angiotensin II receptor blockers.
Hypertension is the most common of the cardiovascular risk factors. Although its risks have been known for decades, hypertension remains inadequately diagnosed and undertreated. Better understanding of the pathophysiology of hypertension, including the role of the renin-angiotensin system, has led to the development of new approaches for patient management. Compared with traditional antihypertension treatments, angiotensin II receptor antagonists may offer more effective treatment and an improved side effect profile. These agents also may have an important treatment role in other cardiovascular conditions for which ACE inhibitors are commonly prescribed. As clinical trial data are showing, the full potential of these drugs has yet to be determined.


Sensitivity thresholds of groundwater parameters for detecting CO2 leakage at a geologic carbon sequestration site.
Geologic carbon sequestration (GCS) projects in the USA are required to monitor groundwater quality for geochemical changes above the injection area that may be a result of CO2 or brine leakage from the storage reservoir. Should CO2 migrate into the groundwater around the compliance wells monitoring the shallower hydrologic units, each compliance parameter could react differently depending on its sensitivity to CO2. Statistically determined limits (SDLs) for detection of CO2 leakage into groundwater were calculated using background water quality data from the Illinois Basin Decatur Project (IBDP) sequestration site and prediction and tolerance intervals for specific compliance parameters. If the parameter concentrations varied outside of these ranges during the injection and post injection periods of a GCS project, then additional actions would be required to determine the reason for the changes in groundwater concentrations. Geochemical modeling can simulate the amount of CO2 needed to alter water quality parameters a statistically significant amount. This information can then inform GCS operators and regulators as to which compliance parameters are relevant (sensitive) to CO2 leakage for a given setting. For the system studied in here, Fe, Ca, K, Mg, CO2, and pH were sensitive to CO2 addition while Al, Cl, Na, and Si were not.


Palliation of Thirst in Intensive Care Unit Patients: Translating Research Into Practice.
Thirst is prevalent among patients in intensive care units. A research-based "thirst bundle" was shown to significantly decrease thirst in these patients. To implement a research-based thirst intervention performed by intensive care unit nurses and patients' family members. Nurses and family members were taught the thirst intervention through video training and project team reinforcement. The intervention was performed by nurses for 123 patients and by family members for 13 patients. Thirst was measured with a numeric rating scale of 0 to 10, a word scale of 0 to 3, or "yes/no" answers, whichever was easiest for the patient. Inferential statistics were used to assess changes in thirst scores over time. Also assessed were nurse and family member burden levels, family level of satisfaction, and patient enjoyment. Thirst scores on the numeric rating scale decreased significantly: from a mean (SD) of 7.9 (2.0) before to 3.9 (2.7) after the intervention for nurses (P < .001); and from 9.2 (1.5) to 5.3 (2.6) for family members (n = 13; P = .002). Word scale scores also decreased significantly, from a median (interquartile range) of 3 (3-3) before to 2 (1-2) after the intervention for nurses (P < .001). Most patients (96%) reported enjoying the procedure. Median burden levels were less than 2 on a numeric rating scale of 0 to 10. The palliative "thirst bundle" significantly alleviated patients' thirst and resulted in little caregiver burden. Further efforts are warranted to incorporate this intervention into intensive care unit practice.


Effect of hyperoxic exposure on protein synthesis in the rat.
Rates of protein synthesis were measured in vivo [corrected] in the lung and heart from fed rats exposed to hyperoxia (less than or equal to 95% O2) for either 6 or 24 h. Protein synthesis rates were depressed by 16-32% compared with normoxic controls in these tissues. The inhibition in both tissues was greatest after 24 h hyperoxic exposure. The decreased fractional rates of synthesis in both tissues were related to changes in ribosomal activity rather than capacity. The fall in synthesis rate per ribosome was greatest in both tissues when the exposure period was increased to 24 h. The possible mechanism(s) involved in hyperoxia-induced depression of protein synthesis are discussed.


Use of sewage sludge compost as the restoration agent on the degraded soil of Tatarstan.
One of the characteristics of soils in Tatarstan is their low organic matter content. The decrease in soil organic matter is paralleled by declines in soil fertility. One method to reverse this degradation in soil quality is the addition of organic matter. The use of sewage sludge on soils intended for growing of plant seedlings provides an alternative for sewage sludge disposal. Therefore, the evaluation of the feasibility of using compost from the municipal sewage sludge produced in Kazan for the soil restoration and growth of Pinus silvestris seedlings was carried out. The grey forest soil (Haplic Greyzem) was amended with compost at application rate 30, 60 and 90 Mg ha(-1) on a dry matter basis. Organic matter content increased with the increase in sludge amendment. The concentrations of individual heavy metal were below the current limits established for Russia and European countries. Sludge amendments enhanced the germination and the number of the seedlings and the increase were more obvious for the soil with highest sludge treatment. The application of composted sludge to soil was followed by the increase in microbial biomass and basal respiration.


Psychiatry Residency Directors' Attitudes Toward and Uses of the Medical Student Performance Evaluation and Other Potential Tools for Residency Selection.
A survey was conducted to determine US psychiatry residency directors' attitudes regarding current measures of medical student performance and their preferences for the future. A team of psychiatry medical student educators and residency program directors developed a 23-question survey. In July 2021, links to the survey were sent out to all program directors registered with the American Association of Directors of Psychiatric Residency Training. Seventy program directors out of 223 initiated the survey, resulting in a response rate of 31.4%. Forty percent of respondents reported that the most important use of the Medical Student Performance Evaluation (MSPE) is in screening out applicants for interviews, and only 26.1% reported that the MSPE in its current form could be trusted to provide a valid and reliable assessment of a student's medical school performance. Most respondents agreed that in the absence of United States Medical Licensing Examination (USMLE) step 1 numerical scores, the existing MSPE format/content requirements should be modified, use a set of ranking categories that are uniform across all medical schools, and be supplemented with additional measures of the student's character and ability specific to psychiatry. US psychiatry program directors are eager for change when it comes to the MSPE and how it reports rankings, grades, and professionalism. The transition of the USMLE step 1 score reporting to pass/fail presents an opportunity to pursue this change and for stakeholders from all medical specialties to work together toward a shared goal of an improved residency selection process.


Ultraviolet radiation and skin carcinogenesis.
The incidence of skin cancer has increased over the last 30 years. Although the role of ultraviolet radiation in human skin carcinogenesis has been supported by a wealth of epidemiological data, the mechanisms by which it leads to skin cancer are still poorly understood. This article reviews recent developments in understanding of the epidemiology and molecular biology of skin carcinogenesis.


Purification and characterization of two phospho-β-galactosidases, LacG1 and LacG2, from Lactobacillus gasseri ATCC33323(T).
Lactobacillus gasseri ATCC33323(T) expresses four enzymes showing phospho-β-galactosidase activity (LacG1, LacG2, Pbg1 and Pbg2). We previously reported the purification and characterization of two phospho-β-galactosidases (Pbg1 and Pbg2) from Lactobacillus gasseri JCM1031 cultured in lactose medium. Here we aimed to characterize LacG1 and LacG2, and classify the four enzymes into 'phospho-β-galactosidase' or 'phospho-β-glucosidase.' LacG1 and recombinant LacG2 (rLacG2), from Lb. gasseri ATCC33323(T), were purified to homogeneity using column chromatography. Kinetic experiments were performed using sugar substrates, o-nitrophenyl-β-D-galactopyranoside 6-phosphate (ONPGal-6P) and o-nitrophenyl-β-D-glucopyranoside 6-phosphate (ONPGlc-6P), synthesized in our laboratory. LacG1 and rLacG2 exhibited high k(cat)/K(m) values for ONPGal-6P as compared with Pbg1 and Pbg2. The V(max) values for ONPGal-6P were higher than phospho-β-galactosidases previously purified and characterized from several lactic acid bacteria. A phylogenetic tree analysis showed that LacG1 and LacG2 belong to the phospho-β-galactosidase cluster and Pbg1 and Pbg2 belong to the phospho-β-glucosidase cluster. Our data suggest two phospho-β-galactosidase, LacG1 and LacG2, are the primary enzymes for lactose utilization in Lb. gasseri ATCC33323(T). We propose a reclassification of Pbg1 and Pbg2 as phospho-β-glucosidase.


Continuous measurement of cardiac output by inert gas throughflow: comparison with thermodilution.
The throughflow method is a new technique for continuous and minimally invasive measurement of cardiac output by the Fick principle, which uses ventilation of the 2 lungs with unequal inspired gas concentrations by means of a double-lumen endobronchial tube. It exploits steady-state gas exchange and thus permits rapid repetition of measurement. Comparison of paired measurements by the throughflow method using N(2)O exchange with bolus thermodilution. Departments of anesthesiology in 2 university teaching hospitals. Nine patients undergoing cardiac surgery in the precardiopulmonary bypass period. Patients intubated with a double-lumen endobronchial tube were ventilated with 45% nitrous oxide (N(2)O) to the left lung (zero to the right lung). Arterial blood gas samples were taken to measure alveolar deadspace to allow correction for the alveolar-arterial N(2)O difference and to correct for the presence of unmeasured shunt perfusion. Throughflow measurements correlated with thermodilution (r = 0.719, p < 0.05) with a mean bias of -0.208 L/min (-5.2%). The standard error of the bias was 0.060 L/min, with 95% confidence limits for the bias of -0.088 L/min and -0.328 L/min. The limits of agreement between the 2 methods were +0.960 L/min and -1.376 L/min. The throughflow method showed good agreement with thermodilution. It permits continuous cardiac output measurement without the need for sampling of mixed venous blood, using techniques of lung isolation, which are readily available in clinical anesthetic practice.


Calcium currents in the A7r5 smooth muscle-derived cell line. Calcium-dependent and voltage-dependent inactivation.
Inactivation of a dihydropyridine-sensitive calcium current was studied in a cell line (A7r5) derived from smooth muscle of the rat thoracic aorta. Inactivation is faster with extracellular Ca2+ than with Ba2+. In Ba2+, inactivation increases monotonically with depolarization. In Ca2+, inactivation is related to the amount of inward current, so that little inactivation is seen in Ca2+ for brief depolarizations approaching the reversal potential. Longer depolarizations in Ca2+ reveal two components of inactivation, the slower component behaving like that observed in Ba2+. Furthermore, lowering extracellular Ca2+ slows inactivation. These results are consistent with the coexistence of two inactivation processes, a slow voltage-dependent inactivation, and a more rapid current-dependent inactivation which is observable only with Ca2+. Ca(2+)-dependent inactivation is decreased but not eliminated when intracellular Ca2+ is buffered by 10 mM BAPTA, suggesting that Ca2+ acts at a site on or near the channel. We also studied recovery from inactivation after either a short pulse (able to produce significant inactivation only in Ca2+) or a long pulse (giving similar inactivation with either cation). Surprisingly, recovery from Ca(2+)-dependent inactivation was voltage dependent. This suggests that the pathways for recovery from inactivation are similar regardless of how inactivation is generated. We propose a model where Ca(2+)- and voltage-dependent inactivation occur independently.


The origin and evolution of G protein-coupled receptor kinases.
G protein-coupled receptor (GPCR) kinases (GRKs) play key role in homologous desensitization of GPCRs. GRKs phosphorylate activated receptors, promoting high affinity binding of arrestins, which precludes G protein coupling. Direct binding to active GPCRs activates GRKs, so that they selectively phosphorylate only the activated form of the receptor regardless of the accessibility of the substrate peptides within it and their Ser/Thr-containing sequence. Mammalian GRKs were classified into three main lineages, but earlier GRK evolution has not been studied. Here we show that GRKs emerged at the early stages of eukaryotic evolution via an insertion of a kinase similar to ribosomal protein S6 kinase into a loop in RGS domain. GRKs in Metazoa fall into two clades, one including GRK2 and GRK3, and the other consisting of all remaining GRKs, split into GRK1-GRK7 lineage and GRK4-GRK5-GRK6 lineage in vertebrates. One representative of each of the two ancient clades is found as early as placozoan Trichoplax adhaerens. Several protists, two oomycetes and unicellular brown algae have one GRK-like protein, suggesting that the insertion of a kinase domain into the RGS domain preceded the origin of Metazoa. The two GRK families acquired distinct structural units in the N- and C-termini responsible for membrane recruitment and receptor association. Thus, GRKs apparently emerged before animals and rapidly expanded in true Metazoa, most likely due to the need for rapid signalling adjustments in fast-moving animals.


Cell-mediated immunity during syphilis.
Evidence is presented which reinforces the complexity of the host-parasite interaction during the course of syphilis. Infection with Treponema pallidum evokes a complicated antibody response and an assortment of cell-mediated immune reactions in the host. It appears that humoral immunity plays a minor role towards the complete elimination of syphilitic infection while the cellular limb of the immune response may be an important host defence mechanism. Information now available indicates that a state of anergy, or immunosuppression, exists in the early stages of human and experimental rabbit syphilis based upon negative skin reactions to T. pallidum antigen(s), the abnormal histological appearance of lymphoid organs, and impaired in vitro lymphocyte reactivity. It is also evident that in the later stages of the disease cellular immunity becomes activated as delayed type skin reactions can normally be elicited in tertiary syphilitics and lymphocyte behaviour in cell culture appears normal. Several mechanisms have been invoked to explain the delay in an effective immune response against syphilitic infection and the duration of the disease: (1) a capsule-like substance on the outer surface of virulant T. pallidum may act as a barrier against treponemicidal antibody; (2) this material and other biological properties of virulent treponemes could enable spirochaetes to escape being engulfed by macrophages and other phagocytic cells; (3) antigenic competition among different treponemal antigens causing partial tolerance; (4) T. pallidum infection may bring about the elaboration of immunosuppressive substances of host or treponemal origin which inhibit the proper function of lymphocytes, macrophages, and other cell types.


Comparison of changes in heart rate variability and sacral skin perfusion in response to postural changes in people with spinal cord injury.
The current clinical practice has established guidelines to assess influences of severity of autonomic injury on the control of heart and blood pressure following spinal cord injury (SCI). However, the influences of SCI-induced autonomic impairment on microvascular dysfunction have not yet been established. Heart rate variability (HRV) has been shown to be a potential tool for quantifying residual sympathovagal regulation of the cardiovascular system following SCI and may be used to assess the effect of autonomic injury on skin microvascular dysfunction. A total of 26 people were recruited into the study, including 12 people with SCI and 14 nondisabled controls. HRV and sacral skin intervals and sacral skin perfusion were continually recorded during 10 min upright and 10 min prone postures. The sympathovagal balance was defined as the ratio of the power of the low frequency to the high frequency of HRV. The results showed that postural changes of nondisabled people produced significant changes in the sympathovagal balance; lower sympathovagal balance was associated with higher skin perfusion (p < 0.05). People with SCI did not show a significant change of HRV and skin perfusion in response to postural changes. In this study, we have demonstrated that the sympathovagal balance assessed by HRV was associated with the skin vasoconstrictive response to postural changes.


The coexistence of traditional medicine and biomedicine: A study with local health experts in two Brazilian regions.
This study investigated the combined use of traditional medicine and biomedicine by local experts in Chapada do Araripe communities (Ceará State) and maroon communities (Santa Catarina State), Brazil. The objective was to understand the perception of local health specialists regarding the number of healers, demand for healers and use of medicinal plants, and the dependence of different environments to obtain such plants. We also aimed to understand the role of medicinal plants to treat different categories of diseases and if there is a complementary use of medicinal plants and allopathic biomedicine, according to the context of each group. The research was conducted with local health specialists that answered structured interviews, created free lists and participated in guided tours to collect cited plants. Sixty-six local health specialists were identified in the Araripe communities and 22 specialists in the maroon communities. In the maroon communities, a greater number of specialists thought there was a decrease in the number and demand for healers, as well as the use of medicinal plants, due to changes in traditional livelihoods, since they are located in a region where the effects of the modernization were more intense. In the Chapada do Araripe communities the specialists knew more plants extracted from native vegetation, whereas in the maroon communities cultivated plants were better known, which may reflect the environmental conditions and the history of each region. Medicinal plants are preferred to treat simpler health problems that do not require medical care, such as gastrointestinal problems, general pain, flues and colds. The biomedicine is used principally for problems with blood pressure, general pains and endocrine and nutritional diseases. Even with the particularities of each region, in general the use of medicinal plants and biomedicines occurred in a complementary form in both regions; however, this coexistence may result from these different contexts. This study also found that there was knowledge and appreciation for traditional health practices in both regions.


Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis.
To assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy. Orthotopic bladder tumours were established in nude mice with KU7 and 253J B-V cells expressing luciferase. BLI and MRI were performed weekly. Tumour volume was calculated from MR images at each time point. Autopsy was performed 4 weeks after inoculation and 45 min after injection of piminidazole. haematoxylin and eosin staining and immunohistochemical analysis of piminidazole adduct formation were performed on 1-mm step-sections through frozen whole bladder specimens to assess necrosis and hypoxia, respectively. CD31 staining was used to evaluate vascularity. Relative volumes of each specimen containing total tumour, hypoxic tumour and necrotic tumour were quantified. The correlation between MRI volume and BLI was weak in KU7 xenografts (R(2) < 0.1) but strong in 253J B-V (R(2) = 0.93 at 4 weeks). KU7 xenografts had vasculature only peripherally and showed extensive hypoxic and necrotic areas. After subtraction of necrotic areas, the correlation of BLI to viable tumour volume improved (R(2) = 0.42). The correlation between tumour BLI and tumour size varies by cell line and is poor in xenografts that rapidly outgrow their vascular supply and develop broad areas of hypoxia and necrosis. However, in these cases BLI does yield information about the amount of viable tumour, and should therefore still be considered as a useful imaging method.


Perfringolysin O Theta Toxin as a Tool to Monitor the Distribution and Inhomogeneity of Cholesterol in Cellular Membranes.
Cholesterol is an essential structural component of cellular membranes in eukaryotes. Cholesterol in the exofacial leaflet of the plasma membrane is thought to form membrane nanodomains with sphingolipids and specific proteins. Additionally, cholesterol is found in the intracellular membranes of endosomes and has crucial functions in membrane trafficking. Furthermore, cellular cholesterol homeostasis and regulation of de novo synthesis rely on transport via both vesicular and non-vesicular pathways. Thus, the ability to visualize and detect intracellular cholesterol, especially in the plasma membrane, is critical to understanding the complex biology associated with cholesterol and the nanodomains. Perfringolysin O (PFO) theta toxin is one of the toxins secreted by the anaerobic bacteria Clostridium perfringens and this toxin forms pores in the plasma membrane that causes cell lysis. It is well understood that PFO recognizes and binds to cholesterol in the exofacial leaflets of the plasma membrane, and domain 4 of PFO (D4) is sufficient for the binding of cholesterol. Recent studies have taken advantage of this high-affinity cholesterol-binding domain to create a variety of cholesterol biosensors by using a non-toxic PFO or the D4 in isolation. This review highlights the characteristics and usefulness of, and the principal findings related to, these PFO-derived cholesterol biosensors.


Spo13 protects meiotic cohesin at centromeres in meiosis I.
In the absence of Spo13, budding yeast cells complete a single meiotic division during which sister chromatids often separate. We investigated the function of Spo13 by following chromosomes tagged with green fluorescent protein. The occurrence of a single division in spo13Delta homozygous diploids depends on the spindle checkpoint. Eliminating the checkpoint accelerates meiosis I in spo13Delta cells and allows them to undergo two divisions in which sister chromatids often separate in meiosis I and segregate randomly in meiosis II. Overexpression of Spo13 and the meiosis-specific cohesin Rec8 in mitotic cells prevents separation of sister chromatids despite destruction of Pds1 and activation of Esp1. This phenotype depends on the combined overexpression of both proteins and mimics one aspect of meiosis I chromosome behavior. Overexpressing the mitotic cohesin, Scc1/Mcd1, does not substitute for Rec8, suggesting that the combined actions of Spo13 and Rec8 are important for preventing sister centromere separation in meiosis I.


Parenting an infant during alcohol recovery.
This qualitative study explored women's concurrent experiences of alcohol/drug recovery while parenting an infant. The study explored women's experiences of recovery from alcohol/drug dependence during the first year after their infant's birth. Balancing emerged as the process that explained how women successfully integrated the recovery and motherhood processes into their identity. Understanding the balancing process will increase sensitivity of care.


Ulcerative colitis and HLA phenotype.
The distribution of HLA A, B, C, DR antigens was investigated in a British population with ulcerative colitis. Fifty six patients were typed for HLA, A, B, C and 46 additionally for DR. No association was found between the HLA phenotype and the presence or absence of ulcerative colitis. Serum from 52 patients was tested for the presence of the anticolon antibody. There was no relation between the presence of the antibody and the HLA phenotype. Finally, no correlation was found between the HLA phenotypes, the age of onset of the disease, the extent and the clinical course.


Infrapatellar fat pad osteochondroma: three cases and a systematic review.
Extraskeletal para-articular osteochondromas of the infrapatellar fat pad are unique soft-tissue tumors whose etiology and clinical history remain poorly understood. We report three cases and a systematic review of the literature. Three females, aged 47, 54, and 70 years, presented with pain and a parapatellar knee mass. All three underwent marginal excision with no complications and no recurrence. In the literature, 32 reports describing 42 cases were identified. Mean age at presentation was 51.1 years (range: 12-75). There were 25 females and 20 males. Seven patients (15.6%) had a history of antecedent trauma. Mean duration of presenting symptoms was 63.9 months (range: 2-300). All patients except for one underwent open excision. Mean follow-up was 14.9 months (range: 3-96). There were no reports of recurrence or malignant transformation. Para-articular extraskeletal osteochondromas of the infrapatellar fat pad have a benign clinical history regardless of whether they are managed by arthroscopic or open marginal excision.


Properties of channels reconstituted from the major intrinsic protein of lens fiber membranes.
Detergent-solubilized plasma membrane protein of either adult bovine or calf lens and high-performance liquid chromatography-purified major intrinsic protein (MIP) of the lens were reconstituted into unilamellar vesicles and planar lipid bilayers. Freeze-fracture studies showed that the density of intramembrane particles in the vesicles was proportional to the protein/lipid ratio. At high ratios, these particles crystallized into tetragonal arrays as does MIP in lens fibers. Channels induced by either purified MIP or detergent-solubilized protein had essentially identical properties. The conductance of multichannel membranes was maximal near 0 mV and decreased to 0.49 +/- 0.08 of the maximum value at voltages greater than 80 mV. The dependence of the conductance on voltage was well fit by a two-state Boltzmann distribution. Voltage steps greater than 30 mV elicited an ohmic current step followed by a slow (seconds) biexponential decrease. The amplitudes and time constants depended on the magnitude but not the sign of the voltage. Steps from 100 mV to voltages less than 30 mV caused the channels to open exponentially with a millisecond time constant. Analysis of latency to first closure after a voltage step gave nearly the same time constants as multichannel kinetics. Single-channel conductance is proportional to salt concentration from 0.1 to 1.0 M in KCl. In 0.1M KCl, the channel had two preferred conductance states with amplitudes of 380 and 160 pS, as well as three additional substates. Multi- and single-channel data suggest that the channel has two kinetically important open states. The channel is slightly anion selective. The properties of the channel do not vary appreciably from pH 7.4 to 5.8 or from pCa 7 to 2. We propose that a channel with these properties could contribute to maintenance of lens transparency and fluid balance.


Ecotoxicity of microplastics to freshwater biota: Considering exposure and hazard across trophic levels.
In contrast to marine ecosystems, the toxicity impact of microplastics in freshwater environments is poorly understood. This contribution reviews the literature on the range of effects of microplastics across and between trophic levels within the freshwater environment, including biofilms, macrophytes, phytoplankton, invertebrates, fish and amphibians. While there is supporting evidence for toxicity in some species e.g. growth reduction for photoautotrophs, increased mortality for some invertebrates, genetic changes in amphibians, and cell internalization of microplastics and nanoplastics in fish; other studies show that it is uncertain whether microplastics can have detrimental long-term impacts on ecosystems. Some taxa have yet to be studied e.g. benthic diatoms, while only 12% of publications on microplastics in freshwater, demonstrate trophic transfer in foodwebs. The fact that just 2% of publications focus on microplastics colonized by biofilms is hugely concerning given the cascading detrimental effects this could have on freshwater ecosystem function. Multiple additional stressors including environmental change (temperature rises and invasive species) and contaminants of anthropogenic origin (antibiotics, metals, pesticides and endocrine disruptors) will likely exacerbate negative interactions between microplastics and freshwater organisms, with potentially significant damaging consequences to freshwater ecosystems and foodwebs.


Enzymatic synthesis of oligosaccharides: product removal during a kinetically controlled reaction.
In this article, the enzymatic production of oligosaccharides, which is an example of a kinetically controlled reaction, is studied. The aim is to show that the product yield can be enhanced by continuous removal of oligosaccharides from the reaction mixture. The oligosaccharides were removed by adsorption on activated carbon. The absorption could be described by the multicomponent Langmuir isotherm with different maximum saturation constants for mono-, di-, and trisaccharides. The affinity for trisaccharides was larger (k(tri) = 3.52 l/g) than for di- (k(di) = 0.94 l/g) and monosaccharides (k(mono) = 0.11 l/g). A model combining kinetics, adsorption on activated carbon, and mass transfer in an adsorption column was developed. Model calculations for the batch process with removal showed a yield improvement of 23% compared to the batch process without removal. Experimentally, a yield improvement of 30% was obtained. Model calculations for the continuous process studied did not result in an increase of the yield. The advantages of removal were masked by the negative influence of recirculation and the relative large time between formation and removal.


Give science and peace a chance: Speeches by Nobel laureates in the sciences, 1901-2018.
The paper presents the results of a quantitative analysis of speeches by Nobel laureates in the sciences (Physics, Chemistry, Medicine) at the Prize gala dinner throughout the whole history of the Prize, 1901-2018. The results outline key themes and historical trends. A dominant theme, common to most speeches, is the exaltation of science as a profession by the laureate. Since the 1970s, especially in chemistry, this element becomes more domain-specific and less related to science in general. One could speculate whether this happens chiefly in chemistry because its area of activity has been perceived to be at risk of erosion from competing fields (e.g. physics, biology). Over time, speeches become more technical, less ceremonial and more lecture-oriented. Emphasis on broad, beneficial impact of science for humanity and mankind (as emphasised in Nobel's will) is more present in laureates' speeches during the first half of the XXth century, while its relevance clearly declines during the last decades. Politics and its relationship with science is also a relevant topic in Nobel speeches. Particularly between the two World Wars, science is seen as terrain where nationalistic stances and fights among nations could actually find a context for peaceful competition and even cooperation.


Home Environment as a Predictor of Long-Term Executive Functioning following Early Childhood Traumatic Brain Injury.
This study examined the relationship of the home environment to long-term executive functioning (EF) following early childhood traumatic brain injury (TBI). Participants (N=134) were drawn from a larger parent study of 3- to 6-year-old children hospitalized for severe TBI (n=16), complicated mild/moderate TBI (n=44), or orthopedic injury (OI; n=74), recruited prospectively at four tertiary care hospitals in the United States and followed for an average of 6.8 years post-injury. Quality of the home environment, caregiver psychological distress, and general family functioning were assessed shortly after injury (i.e., early home) and again at follow-up (i.e., late home). Participants completed several performance-based measures of EF at follow-up. Hierarchical regression analyses examined the early and late home environment measures as predictors of EF, both as main effects and as moderators of group differences. The early and late home environment were inconsistent predictors of long-term EF across groups. Group differences in EF were significant for only the TEA-Ch Walk/Don't Walk subtest, with poorer performance in the severe TBI group. However, several significant interactions suggested that the home environment moderated group differences in EF, particularly after complicated mild/moderate TBI. The home environment is not a consistent predictor of long-term EF in children with early TBI and OI, but may moderate the effects of TBI on EF. The findings suggest that interventions designed to improve the quality of stimulation in children's home environments might reduce the long-term effects of early childhood TBI on EF. (JINS, 2018, 24, 11-21).


Eyelid botulinum toxin injections for the dry eye.
The injection of botulinum toxin into the medial lower eyelid causes a local paralysis of the orbicularis oculi muscle. The paralysis leads to a decreased action of the lacrimal pump and an improved lubrication of the ocular surface. The injection reduces the discomfort in eyes of patients with Sjögren's syndrome.


U.S. Military Medical Evacuation and Prehospital Care of Pediatric Trauma Casualties in Iraq and Afghanistan.
Background: Traumatic injuries were the most common reason for pediatric admission to military hospitals during the recent wars in the Middle East. We describe injury characteristics and prehospital interventions performed on wartime pediatric trauma casualties in Afghanistan and Iraq, stratified by medical evacuation platform. Methods: We queried the Department of Defense Trauma Registry (DODTR) for all pediatric (age < 18 years) encounters from January 2007 to January 2016. The DODTR is the data repository for all trauma-related injuries managed by deployed US military medical treatment facilities with surgical capabilities. We requested all documented prehospital care, which may have been delivered anywhere from the point-of-injury until a fixed-facility with surgical capabilities. We stratified subjects according to Centers for Disease Control age groupings: <1 year, 1-4 years, 5-9 years, 10-14 years, and 15-17 years. Results: Of the 3,493 pediatric encounters in the DODTR, 1,004 underwent military evacuation from the point of injury: 911 (90.7%) by standard medical evacuation platforms and 93 (9.3%) by nonstandard, improvised evacuation assets. Six hundred seventy-five of the 1004 pediatric trauma casualties were between 5 and 14 years of age. Over 75% were male, over 80% were in Afghanistan, and most were injured by explosives. Across all age groups, serious injuries to the head/neck and extremities were most common. Subjects transported by standard evacuation platforms underwent tourniquet application (12.2% vs 5.3%, p < 0.05) and intraosseous access (12.2% vs 4.3%; p = 0.02) more frequently than those on nonstandard platforms. Casualties evacuated by nonstandard platforms underwent airway adjunct emplacement more frequently those on standard evacuation assets (3.2% vs 0.3%; p = 0.01). IV access and opiate administration were the most commonly performed interventions on both standard and nonstandard assets. Subject survival to hospital discharge was 88.1% on standard platforms and 89.2% on nonstandard platforms (p = 0.75). Conclusions: Approximately 30% of pediatric trauma casualties in Afghanistan and Iraq underwent medical evacuation from the point of injury directly to a military treatment facility with surgical capabilities. Most of those children did not undergo the prehospital interventions studied. Future investigations evaluating pediatric medical evacuation and prehospital care, medical staffing, pediatric-specific training, and equipping of pediatric-specific materials may be beneficial.


Analysis of CpG suppression in methylated and nonmethylated species.
The development of nearest-neighbor analysis led to the finding that the frequency of the dinucleotide CpG is markedly depressed in vertebrates. One explanation of this suppression is that methylation of CpG found in vertebrates represents a mutational hot spot through deamination of methylcytidine to thymidine. We have examined the role of methylated CpG as a factor in CpG suppression by comparing CpG distributions in coding regions of 121 genes from six species, three with methylated DNA and three with nonmethylated DNA. Overall base composition shows that all species exhibit CpG suppression, with the methylated forms showing significantly greater suppression than nonmethylated forms. When the data are analyzed by CpG position, the mean values of the methylated forms exhibit greater suppression than nonmethylated forms at positions I-II and II-III, but there is considerable overlap of suppression scores for individual species. At position III-I, CpG suppression is marked in all methylated species, and it is reversed in all nonmethylated species. Our analysis supports the hypothesis that CpG patterns at positions II-III and III-I in methylated forms are affected by mutation acting through deamination of methylcytidine to thymidine. We speculate that the excess of CpGs at position III-I in nonmethylated forms may be related to a requirement for minimal thermal stability of the DNA.


[Family expenses caused by pediatric hospitalization in Niamey (Niger)].
In Niger, 54.4% of the population live below the poverty level (less than 750 FF per year per person). The government is currently implementing a policy to reduce medical costs, including those of hospitals. We carried out a study during the rainy and dry seasons of 1994-1995, of 80 children, randomly selected, who had been admitted to the pediatric ward of Niamey National Hospital. The total expenditure of their families, due to their hospitalization, was recorded and analyzed. The total expenses of the family were 151.8 (+/- 100.0) to 185.5 (+/- 118.9) FF depending on where the drugs were purchased (wholesale or private). Medical expenses accounted for 98.0 (+/- 48.3) to 119.8 (+/- 57.2) FF, that is 60.0 to 64.5% of total expenses. Non-medical expenses (transport, food, presents) accounted for 61.7 to 65.7 FF, 35.4 to 39.9%. Total daily expenses were 23 to 41.7 FF for the five main diseases. In 66 cases, the costs were paid by the father (82.5%), with the mother or another person paying in 7 cases (8.8%). Only 24 families (30%) paid the hospital fee (10.5 FF). Twenty-seven families were exempted and 22 avoided payment. The cost of medical analysis was 32.6 (+/- 31.3) FF and this was paid by the hospital. The total cost (total family expenditure + hospital expenditure) of a stay in a pediatric unit was 316.5 to 350.4 FF, which is equivalent to 8 to 10 times the mean annual individual expenditure on health in urban areas of Niger. Measures have already been introduced to encourage the prescription of generic drugs and a number of measures are currently under discussion for lowering the cost to families of hospital and health center care and for improving the cost effectiveness of treatment.


The Significance of Antibodies against Domain I of Beta-2 Glycoprotein I in Antiphospholipid Syndrome.
The antiphospholipid syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPLs). Progress is being made in understanding the pathogenesis of the syndrome, but difficulties persist in the identification of patients at risk for thrombosis and/or pregnancy morbidity. Beta-2 glycoprotein I (β2GPI), a plasma protein consisting of five sushi domains, is thought to be the main antigenic target of aPLs. Antibodies recognizing domain I of β2GPI are predominantly present in patients with an elevated risk of thrombosis, whereas antidomain IV/V antibodies are found in nonthrombotic autoimmune diseases. Indeed, domain I antibodies proved to be pathogenic in multiple studies. Retrospective studies have provided evidence for an added clinical value of antidomain I antibodies in the risk stratification of patients with APS. Still, wide ranges of odds ratio exist between studies, probably due to differences in the study and control population, and detection methods used. Despite the proven pathogenicity of antidomain I antibodies and their correlations with clinical manifestations of APS, heterogeneity of the current studies has prohibited their acceptance in the official diagnostic criteria. Well-designed large longitudinal prospective studies with available and new, preferentially functional, assays for the risk stratification of patients with APS are required.


Quality of reporting randomized controlled trials (RCTs) in the nursing literature: application of the consolidated standards of reporting trials (CONSORT).
In the era of evidence-based practice (EBP), Randomized Controlled Trials (RCTs) may provide the best evidence of the efficacy of nursing interventions and yet the quality of RCT reporting in nursing literature has not been evaluated. The purposes of this study were to apply the Consolidated Standards of Reporting Trials (CONSORT) statement to published reports of nursing science, examine how adequately the published reports adhere to the statement, and examine the effect of the adoption of CONSORT on the quality of the RCT published reports. One hundred RCTs from 2002-2005 were identified from 4 nursing journals. Articles were randomly assigned to 4 reviewers and the quality of the published reports was evaluated using a modified CONSORT checklist. There was no difference between the 4 journals in the quality of the published reports of RCTs based on the modified CONSORT checklist employed (F = 1.27, P =.29). The quality of reporting of RCTs improved significantly in the only journal, Nursing Research, to adopt the CONSORT statement during the study period (t =-2.70, P =.01). Adoption of CONSORT is recommended as it may lead to an overall improvement in quality of reporting of RCTs in nursing journals. The profession may also wish to explore the use or development of standards similar to CONSORT but ones more appropriate for the types of research typical of that published by nurse scientists.


Exploring the Abnormal Modulation of the Autonomic Systems during Nasal Flow Limitation in Upper Airway Resistance Syndrome by Hilbert-Huang Transform.
Patients with nasal flow limitation and upper airway resistance syndrome (UARS) during sleep can present with low blood pressure and disturbing symptoms associated with hypervagotony. We hypothesized that the dynamic changes of the autonomic system related to inspiratory flow limitation can be quantified by the developed analytic technique applied on beat-to-beat heart rate (RR intervals) and finger photoplethysmography (PPG). A breath-by-breath investigation based on the Hilbert-Huang transform was performed to explore autonomic nervous system changes observed during inspiratory flow limitation. Autonomic status was quantified from beat-to-beat heart rate analysis by high frequency (RRHF; 0.15-0.4 Hz), low frequency (RRLF; 0.04-0.15 Hz), and LF/HF ratio of each respiratory cycle. Based on respiratory-related mechanisms contained in the PPG signal, we further quantified the respiratory-related oscillations (PPGres). Based on esophageal pressure and nasal flow measurements, each respiratory cycle was identified and breathing patterns were classified into one of four groups: normal, inspiratory flow limitation cycles without increased effort [FL(-)], minimal inspiratory flow limitation with effort, and inspiratory flow limitation cycles with increased effort [FL(+)]. The resulting quantitative parameters of the identified cycles were calculated. 49 UARS patients (12 males; aged 26.8 ± 5.8 years) with apnea-hypopnea index (AHI) 3.1 ± 1.5 per hour and nine aged matched control subjects (3 males; aged 27.8 ± 4.0 years) with AHI 0.8 ± 1.1 per hour were retrospectively identified. Compared to the control group, hyperactivation of the parasympathetic system was noted during stage 2 NREM sleep by RRHF (27.8 ± 18.2 vs 22.5 ± 11.12, p < 0.05) in 49 UARS patients. Analysis of the different classifications of respiratory cycles indicated that during "high" (increased) respiratory efforts, the RRHF and PPGres were significantly higher compared to "normal cycle" and "FL(-)" groups. The RRLF/RRHF (an index of sympathetic activity) was significantly lower in the "FL(+)" group (1.66 ± 0.80) than in the "normal cycle" (1.93 ± 0.97, p < 0.05) and "FL(-)" groups (2.01 ± 1.01, p < 0.05). The proposed algorithm allows quantifying the temporal changes of specific mechanisms of the autonomic system on breath-by-breath basis. With no or very limited impact on oxygen saturation, the hyperactivation of parasympathetic system in associated with inspiratory flow limitation or increased respiratory efforts during stage 2 NREM sleep has been presented in this study.


Psychosocial aspects of hereditary cancer (PAHC) questionnaire: development and testing of a screening questionnaire for use in clinical cancer genetics.
Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific psychosocial problems related to cancer genetic counseling. We adopted the European Organisation for Research and Treatment of Cancer Quality of Life Group guidelines to develop the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, a 26-item questionnaire organized into six problem domains: genetics, practical issues, family, living with cancer, emotions, and children. The Distress Thermometer and a question per domain on the perceived need for extra psychosocial services were included as well. We administered the questionnaire and the Hospital Anxiety and Depression Scale to 127 counselees at the time of genetic counseling and 3 weeks after DNA test disclosure. As a gold standard to evaluate the screening properties of the questionnaire, participants underwent a semi-structured interview with an experienced social worker who assessed the presence and severity of problems per domain. A cutoff score representing responses of 'quite a bit' or 'very much' to one or more items within a given problem domain yielded moderate to high sensitivity across domains. A cutoff of 4 on the Distress Thermometer yielded high sensitivity. The questions regarding the perceived need for extra psychosocial services yielded high specificity and negative predictive values. The Psychosocial Aspects of Hereditary Cancer questionnaire in combination with the Distress Thermometer can be used as a first-line screener for psychosocial problems within the cancer genetic counseling setting.


[The treatment of immunological infertility].
In 6 cases antisperm antibodies were demonstrated in the serum of patients. Other causes of infertility were excluded. The patients were treated with corticosteroids; in 5 cases prednisone 5 mg three times daily for 3 months was used, while in 1 case methylprednisolone 96 mg daily for 7 days was used. In 5 patients the antibody titre declined. Three pregnancies resulted.


Reconstruction of propagated electrical activity with a two-dimensional model of anisotropic heart muscle.
The propagated electrical activity in normal anisotropic cardiac muscle is characterized by directionally dependent variations in the rising phase of the action potential. An important question concerns the relation between such variations and the propagation velocity and extracellular potentials. This problem was studied here in a sheet of cells, under conditions of uniform intracellular anisotropic resistivity and constant electrical membrane properties, through a numerical solution of the two-dimensional propagation equation. The numerical solution implies a lumping of the cytoplasmic and intercellular resistances into an equivalent junctional resistance to form a distributed resistive network representing the intracellular domain. The interstitial space is assumed isotropic and unbounded, with a resistivity of 100 omega X cm. The electrical properties of the cell membrane are represented by a Beeler-Reuter model. The stimulus current is applied to a small area of the sheet, and attention is focussed on the stable propagated events occurring some 5 or 6 length constants away from the stimulation site. The numerical solution is a good approximation of a continuous uniform structure when the cell size is less than 10% of the length constant along both major axes. Conditions of non-uniform propagation, with directionally dependent variations in the maximum rate of rise and time constant of the foot of the action potential were simulated by increasing the cell size to 30% of the length constant in the transverse direction of the sheet. Our results indicate that the directional changes in the maximum rate of rise correspond to small modifications of the extracellular potentials, while the directional changes in time constant of the foot are associated with the propagation velocity. The maximum effects are observed along the transverse direction as follows: a 19% increase in maximum rate of rise corresponds to a decrease of about 6% in the peak-to-peak amplitude of the extracellular potential, and a 24% increase in time constant of the foot is associated with a decrease of about 7% in the propagation velocity. Under the conditions of the present study, however, the simulated directional changes in maximum rate of rise are smaller than those experimentally observed so the corresponding changes in the extracellular potentials are probably underestimated.


Disclosure of Sexual Identities Across Social-Relational Contexts: Findings from a National Sample of Black Sexual Minority Men.
Black sexual minority men (BSMM) in the USA navigate a range of factors that may influence the extent to which they disclose or conceal their sexual identity in various social contexts. To date, few studies have investigated the correlates of sexual identity disclosure or concealment among BSMM across multiple life domains. Guided by a minority stress perspective and intersectionality, we analyzed data from N = 809 BSMM who participated in the Social Justice Sexuality Survey. We conducted ordinary least squares regression to examine the relative weight of perceptions of homophobia, religiosity, LGBT community connectedness, racial identity salience, and sexual identity salience on disclosure of sexual identity in six social-relational contexts: (1) family, (2) friends, (3) neighbors, (4) religious community, (5) work, and (6) online. Findings indicate that BSMM disclosed their sexual identity unevenly across social-relational contexts. Notably, LGBTQ community connectedness and sexual identity importance were consistent predictors of sexual identity disclosure across contexts. In contrast, perceptions of homophobia were not related to sexual identity disclosure, suggesting that other factors may be more salient for BSMM when deciding to disclose their sexual identity. Finally, bisexual men consistently reported lower levels of sexual identity disclosure relative to gay men in all six contexts. Study findings have important implications for future research on sexual identity disclosure with diverse samples of BSMM.


Urinary Bisphenols and Obesity Prevalence Among U.S. Children and Adolescents.
Bisphenol A (BPA) has been recognized as an endocrine disrupting chemical and identified as an obesogen. Although once ubiquitous, human exposure to BPA has been declining owing to its substitution with other bisphenols. Two structurally similar substitutes, bisphenol S (BPS) and bisphenol F (BPF), have raised similar concerns, although fewer studies have been conducted on these newer derivatives. We used data from the US National Health and Nutrition Examination Surveys from 2013 to 2016 to evaluate associations between BPA, BPS, and BPF and body mass outcomes among children and adolescents aged 6 to 19 years. Concentrations of BPA, BPS, and BPF were measured in spot urine samples using HPLC with tandem mass spectrometry. General obesity was defined as ≥95th percentile of the age- and sex-standardized body mass index (BMI) z-scores according to the 2000 US norms. Abdominal obesity was defined as a waist circumference/height ratio of ≥0.5. BPA, BPS, and BPF were detected in 97.5%, 87.8%, and 55.2% of urine samples, respectively. Log-transformed urinary BPS concentrations were associated with an increased prevalence of general obesity (OR, 1.16; 95% CI, 1.02 to 1.32) and abdominal obesity (OR, 1.13; 95% CI, 1.02 to 1.27). BPF detection (vs not detected) was associated with an increased prevalence of abdominal obesity (OR, 1.29; 95% CI, 1.01 to 1.64) and continuous BMI z-score (β = 0.10; 95% CI, 0.01 to 0.20). BPA and total bisphenols were not statistically significantly associated with general obesity, abdominal obesity, or any body mass outcome. These results suggest that BPA substitute chemicals are correlated with obesity in contemporary children.


[Can extrachromosomal genetic elements be recognized as inventions?].
The legal bases for acknowledgement of plasmids (vectors) as inventions, in particular within the classes of the "substance" and "microbial strain" are discussed. There is a definite similarity in a number of features between phages recognized as inventions and plasmids. Therefore, in principle their acknowledgement as inventions may be considered possible, since it raises no new problems as those occurring in legal protection of microbial strains. At the same time there is no pressing need in acknowledgement of plasmids (vectors) as inventions and their legal protection should be rather of the prestige character.


Ethics in the absence of truth.
Nurses are passionate about patients' rights; especially the right of all patients to full disclosure, autonomy, and decision making. When these patient rights have been violated by an absence of truth, by deception, or by lies, nurses become unwilling actors in a part they find neither wise nor ethical. This discomfort can negatively impact patient care and contributes to job dissatisfaction. This article examines real-life situations where the principle of veracity has been abused. Suggestions for resolving ethical concerns can help readers to approach similar situations in a new light.


The synthesis, stability and biological activity of bis-intercalating bis-daunomycin hydrazones.
The synthesis of a series of bis-daunomycin hydrazones (5a-g)--all moderately stable at 37 degrees C, pH 6.8, with a half-life of approximately 30 h--is reported. Under a pulse exposure of 2 h they exhibited growth inhibition of mouse L1210 cells, and were 2-3 fold more active than daunomycin. Under continuous exposure growth inhibition conditions with human colon cell lines (HT-29 and HCT-8) they hydrolysed to daunomycin and a partially hydrolysed mono-derivative of daunomycin, and there was no apparent increase in activity over that of the parent anthracycline. Their rate of hydrolysis was observed to increase rapidly with decreasing pH.


Atypical signaling and functional desensitization response of MAS receptor to peptide ligands.
MAS is a G protein-coupled receptor (GPCR) implicated in multiple physiological processes. Several physiological peptide ligands such as angiotensin-(1-7), angiotensin fragments and neuropeptide FF (NPFF) are reported to act on MAS. Studies of conventional G protein signaling and receptor desensitization upon stimulation of MAS with the peptide ligands are limited so far. Therefore, we systematically analyzed G protein signals activated by the peptide ligands. MAS-selective non-peptide ligands that were previously shown to activate G proteins were used as controls for comparison on a common cell based assay platform. Activation of MAS by the non-peptide agonist (1) increased intracellular calcium and D-myo-inositol-1-phosphate (IP1) levels which are indicative of the activation of classical Gαq-phospholipase C signaling pathways, (2) decreased Gαi mediated cAMP levels and (3) stimulated Gα12-dependent expression of luciferase reporter. In all these assays, MAS exhibited strong constitutive activity that was inhibited by the non-peptide inverse agonist. Further, in the calcium response assay, MAS was resistant to stimulation by a second dose of the non-peptide agonist after the first activation has waned suggesting functional desensitization. In contrast, activation of MAS by the peptide ligand NPFF initiated a rapid rise in intracellular calcium with very weak IP1 accumulation which is unlike classical Gαq-phospholipase C signaling pathway. NPFF only weakly stimulated MAS-mediated activation of Gα12 and Gαi signaling pathways. Furthermore, unlike non-peptide agonist-activated MAS, NPFF-activated MAS could be readily re-stimulated the second time by the agonists. Functional assays with key ligand binding MAS mutants suggest that NPFF and non-peptide ligands bind to overlapping regions. Angiotensin-(1-7) and other angiotensin fragments weakly potentiated an NPFF-like calcium response at non-physiological concentrations (≥100 µM). Overall, our data suggest that peptide ligands induce atypical signaling and functional desensitization of MAS.


Arthritis prevalence and activity limitations in older adults.
To evaluate the prevalence of arthritis and activity limitations among older Americans by assessing their demographic, ethnic, and economic characteristics. Data from the Asset and Health Dynamic Survey Among the Oldest Old (AHEAD), a national probability sample of community-dwelling adults born before 1924, were analyzed cross-sectionally. Arthritis that resulted in a physician's visit or a joint replacement not associated with a hip fracture was ascertained by self-report. The prevalence of arthritis in older adults ranged from 25% in non-Hispanic whites to 40% in non-Hispanic blacks to 44% in Hispanics. A higher prevalence of arthritis was associated with less education as well as lower income and less wealth. The prevalence of limitations in activities of daily living (ADL) among non-Hispanic white, non-Hispanic black, and Hispanic adults who reported arthritis only was 29%, 30%, and 37%, respectively, and increased to 48%, 57%, and 56%, respectively, among those reporting arthritis plus other chronic conditions, after adjustment for age and sex. Non-Hispanic black and Hispanic older adults reported having arthritis at a substantially higher frequency than did non-Hispanic whites. In addition, Hispanics reported higher rates of ADL limitations than did non-Hispanic whites with comparable disease burden. Further study is needed to confirm and elucidate the reasons for these racial and economic disparities in older populations.


Estimation of the macromolecular proton fraction and bound pool T2 in multiple sclerosis.
This study used a model for magnetization transfer (MT) to estimate two underlying parameters: the macromolecular proton fraction (f) and the bound pool T2 (T2b) in patients with multiple sclerosis (MS). Sixty patients with clinically definite MS and 27 healthy controls were imaged using: (1) a dual echo fast spin echo sequence, (2) a MT sequence (with ten MT power and offset frequency combinations) and (3) proton density and T1 weighted sequences (for T1 relaxation time estimation). Fourteen normal-appearing white matter (NAWM) regions of interest (ROI) and six normal-appearing gray matter (NAGM) ROIs were outlined in all subjects. Lesions were also contoured in subjects affected by MS. The model was fitted to the data leading to estimates of T2b and f. Results showed that T2b was increased in lesions whereas f was reduced. In NAWM, f was decreased while T2b was only increased in secondary progressive MS. NAWM f correlated modestly with disability. Further studies are needed to investigate the pathological basis of the abnormalities observed.


Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2.
PTEN is a tumor suppressor gene mutated in human cancers. Although many mutations target the phosphatase domain, others create a truncated protein lacking the C-terminal PDZ-binding motif or a protein that extends beyond the PDZ-binding motif. Using the yeast two-hybrid system, we isolated a membrane-associated guanylate kinase family protein with multiple PDZ domains [AIP-1 (atrophin interacting protein 1), renamed MAGI-2 (membrane associated guanylate kinase inverted-2)]. MAGI-2 contains eight potential protein-protein interaction domains and is localized to tight junctions in the membrane of epithelial cells. PTEN binds to MAGI-2 through an interaction between the PDZ-binding motif of PTEN and the second PDZ domain of MAGI-2. MAGI-2 enhances the ability of PTEN to suppress Akt activation. Furthermore, certain PTEN mutants have reduced stability, which is restored by adding the minimal PDZ-binding motif back to the truncated protein. We propose that MAGI-2 improves the efficiency of PTEN signaling through assembly of a multiprotein complex at the cell membrane.


Digital Implant Impression Technique Accuracy: A Systematic Review.
The objective was to provide a comprehensive systematic review about the accuracy of digital implant impression in comparison with the conventional implant impression approach. PubMed, Google Scholar and Cochrane databases were used to classify the related articles with no year limitation in 3 stages by 2 reviewers. Finally, 10 articles were included based on inclusion and exclusion criteria. Five articles supported the use of intraoral scanners in implant dentistry. The two in vivo pilot studies showed that digital scanning is not reliable and could not be used in clinical routine. Because each study included in this review has its unique methodology and design, it is therefore early to conclude whether to use digital scanners for clinical practice or not. More well-conducted in vitro and clinical trials studies are recommended to investigate the accuracy of intraoral scanners.


Muscle force estimation during gait using Angle-EMG-Force relationship.
Measuring the muscle force during gait can provide crucial knowledge for clarifying the walking mechanism and preventing injuries. However, non-invasive muscle force measurement is a major challenge in biomechanics. Previous research has investigated the relationship between the amplitude of electromyography (EMG) and muscle force. By examining the EMG-force relationship of each muscle, the generated muscle force can be measured on the basis of the EMG amplitude during gait. This study aimed to investigate the angle-EMG-force relationship of lower limb muscles and estimate the muscle force during gait. The EMG and muscle force were measured in a static muscle force measurement task, and the angle-EMG-force relationship was analyzed based on these data. The results indicate that the muscle force can be estimated using the angle-EMG-force relationship during gait.Clinical Relevance-This study contributes to a more correct analysis of the muscle force during gait.