Cyclic changes in genital organs and vaginal cytology in cynomolgus monkeys (Macaca fascicularis).
Vaginal cytology was evaluated weekly over 12 months in 20 adult female Cynomolgus monkeys (Macaca fascicularis). After sacrifice of the animals the histology of the ovaries, uterus and vagina were studied in different phases of the menstrual cycle. The cytological examination of the vaginal smears showed that the superficial cells increased in number towards the middle of the cycle and the number of intermediate cells declined gradually. Parabasal cells were observed mainly at the beginning of the cycle; they disappeared towards the middle of the menstrual cycle. During the early follicular phase, the cells were moderately separated from each other, and during the second half of the proliferative or follicular phase, the superficial cells appeared clumped together. Leucocytes were usually absent except for at the beginning of the cycle and in the last few days of the late secretory or luteal phase. The maturation index of the vaginal smears can be considered as a tool for distinguishing the different phases of the menstrual cycle. The microscopic examination of the genital organs showed that during the proliferative or follicular phase of the cycle, which corresponds to the development of the ovarian follicles, the uterus showed growth of endometrial glands, stroma and endothelial cell proliferation with capillary sprouts. Shortly after ovulation and parallel to the formation of the corpora lutea, the endometrium enters the secretory or luteal phase, which is characterized by coiling of endometrial glands, glandular secretion and the differentiation of the spiral artery. The most striking changes in the vagina, is the marked basal cell proliferation and thickening of the stratum granulosum during the follicular phase of the menstrual cycle. The histological changes observed in the vagina demonstrated a good correlation with the observation on cytological examination of the smears. The present study demonstrated that the process of angiogenesis in the uterus during the different phases of the menstrual cycle is a multiple phenomenon involving proliferation, maturation and differentiation.


BRACHYURY confers cancer stem cell characteristics on colorectal cancer cells.
Cancer stem cells (CSCs) are initiating cells in colorectal cancer (CRC). Colorectal tumours undergo epithelial to mesenchymal transition (EMT)-like processes at the invasive front, enabling invasion and metastasis, and recent studies have linked this process to the acquisition of stem cell-like properties. It is of fundamental importance to understand the molecular events leading to the establishment of cancer initiating cells and how these mechanisms relate to cellular transitions during tumourigenesis. We use an in vitro system to recapitulate changes in CRC cells at the invasive front (mesenchymal-like cells) and central mass (epithelial-like cells) of tumours. We show that the mesoderm inducer BRACHYURY is expressed in a subpopulation of CRC cells that resemble invasive front mesenchymal-like cells, where it acts to impose characteristics of CSCs in a fully reversible manner, suggesting reversible formation and modulation of such cells. BRACHYURY, itself regulated by the oncogene β-catenin, influences NANOG and other 'stemness' markers including a panel of markers defining CRC-CSC whose presence has been linked to poor patient prognosis. Similar regulation of NANOG through BRACHYURY was observed in other cells lines, suggesting this might be a pathway common to cancer cells undergoing mesenchymal transition. We suggest that BRACHYURY may regulate NANOG in mesenchymal-like CRC cells to impose a 'plastic-state', allowing competence of cells to respond to signals prompting invasion or metastasis.


Health-related utility values of patients with primary Sjögren's syndrome and its predictors.
EuroQoL-5 dimension (EQ-5D) is a standardised preference-based tool for measurement of health-related quality of life and EQ-5D utility values can be converted to quality-adjusted life years (QALYs) to aid cost-utility analysis. This study aimed to evaluate the EQ-5D utility values of 639 patients with primary Sjögren's syndrome (PSS) in the UK. Prospective data collected using a standardised pro forma were compared with UK normative data. Relationships between utility values and the clinical and laboratory features of PSS were explored. The proportion of patients with PSS reporting any problem in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 42.2%, 16.7%, 56.6%, 80.6% and 49.4%, respectively, compared with 5.4%, 1.6%, 7.9%, 30.2% and 15.7% for the UK general population. The median EQ-5D utility value was 0.691 (IQR 0.587-0.796, range -0.239 to 1.000) with a bimodal distribution. Bivariate correlation analysis revealed significant correlations between EQ-5D utility values and many clinical features of PSS, but most strongly with pain, depression and fatigue (R values>0.5). After adjusting for age and sex differences, multiple regression analysis identified pain and depression as the two most important predictors of EQ-5D utility values, accounting for 48% of the variability. Anxiety, fatigue and body mass index were other statistically significant predictors, but they accounted for <5% in variability. This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.


Assessment of vacuum cleaners and vacuum cleaner bags recommended for allergic subjects.
High-quality vacuum cleaners and vacuum cleaner bags are often recommended to allergic patients as a means of reducing indoor allergen exposure. A number of vacuum cleaners on the market today claim to capture 99.9% of particles 0.3 microm or larger entering the vacuum cleaner, and many vacuum cleaner bags are now being sold as microfiltration bags. The purpose of this study was to compare the allergen-trapping abilities of vacuum cleaners and to use a new technique for testing vacuum cleaner bags that are recommended for allergic patients. Vacuum cleaners were tested in an 18-m(3) laboratory room permeated with dust containing high levels of cat allergen by using techniques previously described. Air was sampled with parallel filters in conjunction with a particle counter. The filters were assayed by ELISA for cat allergen (Fel d 1). Vacuum cleaner bags were tested by using a modified dust trap to pull sieved house dust containing a known amount of Fel d 1 across the material used for the bag. Allergen passing through the bag was trapped on a filter covering the exit of the trap and analyzed for Fel d 1. In general, vacuum cleaners designed for allergic patients leaked lower amounts of allergen (<0.5-4.04 ng/m(3)) than that found in our previous studies (<0.5-100 ng/m(3)). Single-layer vacuum cleaner bags performed poorly (1250-2640 ng recovered) compared with most of the 2- and 3-layer microfiltration bags (0.53-2450 ng recovered). The range of allergen recovered from the 2-layer bags (0.93-2450 ng recovered) highlighted the variability found between manufacturers. The results suggest that although allergen leakage has been reduced, there is still room for improvement. A method of testing allergen leakage by using Fel d 1 should be applied to vacuum cleaners and bags recommended for allergic patients.


Biological adaptations for functional features of language in the face of cultural evolution.
Although there may be no true language universals, it is nonetheless possible to discern several family resemblance patterns across the languages of the world. Recent work on the cultural evolution of language indicates the source of these patterns is unlikely to be an innate universal grammar evolved through biological adaptations for arbitrary linguistic features. Instead, it has been suggested that the patterns of resemblance emerge because language has been shaped by the brain, with individual languages representing different but partially overlapping solutions to the same set of nonlinguistic constraints. Here, we use computational simulations to investigate whether biological adaptation for functional features of language, deriving from cognitive and communicative constraints, may nonetheless be possible alongside rapid cultural evolution. Specifically, we focus on the Baldwin effect as an evolutionary mechanism by which previously learned linguistic features might become innate through natural selection across many generations of language users. The results indicate that cultural evolution of language does not necessarily prevent functional features of language from becoming genetically fixed, thus potentially providing a particularly informative source of constraints on cross-linguistic resemblance patterns.


Self resistance to the atypical cationic antimicrobial peptide edeine of Brevibacillus brevis Vm4 by the N-acetyltransferase EdeQ.
Edeines are atypical cationic peptides produced by Brevibacillus brevis Vm4 with broad-spectrum antimicrobial activity. These linear nonribosomal peptides bind to the 30S ribosomal subunit and block t-RNA binding to the P-site. To identify the mechanism of high-level self-resistance in the producing organism, the B. brevis Vm4 genome was sequenced and the edeine biosynthetic cluster discovered. A potential edeine-modifying enzyme, EdeQ, showed similarity to spermidine N-acetyltransferases. EdeQ was purified and shown to convert edeine to N-acetyledeine, which is inactive against cells in vivo and against cell-free extracts. Unexpectedly, tandem mass spectroscopy and nuclear magnetic resonance demonstrate that N-acylation occurs on the free amine of the internal diaminopropionic acid rather than the N-terminal spermidine polyamine. Acetylation of edeine by EdeQ abolishes its ability to inhibit translation, thus conferring resistance to the antibiotic in the producing organism.


Changing epidemiology of cancer.
At current rates, approximately one in three Canadians will develop cancer, and one in four will die from it. For each sex, three cancer sites account for more than 50% of all new diagnoses and cancer deaths, these being lung, prostate, and colorectum in men and breast, colorectum, and lung in women. Although the total numbers of new cases and cancer deaths have risen, the overall cancer incidence and mortality rates have increased only slightly. The ranking of specific sites have changed, however; most notably, lung cancer has moved from the fifth to the second most common site of cancer death in women since 1970. The authors review trends in cancer incidence and mortality in Canada. Changes in lifestyle and behaviour could reduce cancer incidence and mortality.


Prevention of bacterial adhesion.
Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation. As such, adhesion represents the Achilles heel of crucial pathogenic functions. It follows that interference with adhesion can reduce bacterial virulence. Here, we illustrate this important topic with examples of techniques being developed that can inhibit bacterial adhesion. Some of these will become valuable weapons for preventing pathogen contamination and fighting infectious diseases in the future.


Role of cardiovascular magnetic resonance imaging in arrhythmogenic right ventricular dysplasia.
Arrhythmogenic right ventricular dysplasia (ARVD) is a genetic cardiomyopathy characterized clinically by ventricular arrhythmias and progressive right ventricular (RV) dysfunction. The histopathologic hallmark is fibro-fatty replacement of RV myocardium. It is inherited in an autosomal pattern with variable penetrance. ARVD is unique in that it most commonly presents in young, otherwise healthy and highly athletic individuals. The cause of ARVD is not well-known but recent evidence suggests strongly that it is a disease of desmosomal dysfunction. The disease involvement is not limited only to the RV as left ventricle (LV) has also been reportedly affected. Diagnosis of ARVD is challenging and is currently based upon a multi-disciplinary work-up of the patient as defined by the Task Force. Currently, implanted cardioverter defibrillators (ICD) are routinely used to prevent sudden death in patients with ARVD. Cardiovascular MR is an important non-invasive diagnostic modality that allows both qualitative and quantitative evaluation of RV. This article reviews the genetics of ARVD, current status and role of CMR in the diagnosis of ARVD and LV involvement in ARVD.


Cultural Engagement Is a Risk-Reducing Factor for Frailty Incidence and Progression.
Given that frailty is a multifaceted health condition of increasing importance to policy-makers and care providers, it is relevant to consider whether multimodal interventions could provide combined psychophysiological support. As studies have demonstrated the beneficial effects of cultural engagement (including visiting museums/theatre/cinema) for many of the components of frailty, this study sought to explore whether community cultural engagement is associated both with a reduced risk of becoming frail and a slower trajectory of frailty progression in older adults. We used data from the English Longitudinal Study of Ageing to measure frequency of cultural engagement and both incident frailty and frailty progression over the following 10 years in 4,575 adults. Our analyses used competing risks regression models and multilevel growth curve models adjusting for socioeconomic, health behaviors, social confounders, and subthreshold symptoms of frailty. There was a dose-response relationship between increasing frequency of cultural engagement and both incidence and progression of frailty (attendance every few months or more: incidence subhazard ratio = 0.79, 95% confidence interval [CI] = 0.63 to 0.996; trajectory coefficient = -0.0039, 95% CI = -0.0059 to -0.0019). Older adults who engaged in cultural activities every few months or more had a reduced risk of becoming frail and a slower progression of frailty over time. Findings are in line with current calls for multimodal, multifactor, community approaches to support health in older age.


A Rare Case of Hepatic Sinusoidal Occlusive Syndrome in a Premature Neonate with Trisomy 21.
Trisomy 21 (Down Syndrome) may lead to multiple hematological and hepatobiliary manifestations including the development of transient abnormal myelopoiesis. While many cases resolve, transient abnormal myelopoiesis may lead to significant morbidity and mortality in a small percentage of patients. This condition may present a diagnostic challenge for physicians and currently there is only limited data on effective treatments, particularly with low blast percent transient abnormal myelopoiesis. We present a case of a neonate with trisomy 21 and multiple congenital anomalies who consequently developed hepatic failure with evidence of non-cirrhotic portal hypertension likely due to transient abnormal myelopoiesis. This clinical scenario highlights the need for additional evaluation for transient abnormal myelopoiesis associated hepatic disorder and possibly hepatic sinusoidal occlusive syndrome among trisomy 21 neonates particularly with low blast percentage.


The effects of mating status and time since mating on female sex pheromone levels in the rice leaf bug, Trigonotylus caelestialium.
Although mating status affects future mating opportunities, the biochemical changes that occur in response to mating are not well understood. This study investigated the effects of mating status on the quantities of sex pheromone components found in whole-body extracts and volatile emissions of females of the rice leaf bug, Trigonotylus caelestialium. When sampled at one of four time points within a 4-day postmating period, females that had copulated with a male had greater whole-body quantities of sex pheromone components than those of virgin females sampled at the same times. The quantities of sex pheromone components emitted by virgin females over a 24-h period were initially high but then steadily decreased, whereas 24-h emissions were persistently low among mated females when measured at three time points within the 4 days after mating. As a result, soon after mating, the mated females emitted less sex pheromones than virgin females, but there were no significant differences between mated and virgin females at the end of the experiment. Thus, postmating reduction in the rate of emission of sex pheromones could explain previously observed changes in female attractiveness to male T. caelestialium.


Design and characterization of a microchannel optical interconnect for optical backplanes.
The design, modeling, and experimental characterization of a microchannel-based free-space optical interconnect is described. The microchannel interconnect was used to implement a representative portion of an optical backplane that was based on field-effect transistor, self-electro-optic device smart-pixel transceivers. Telecentric relays were used to form the optical interconnect, and two modes based on two different optical window clusterings were implemented. The optical system design, including the optical geometry for different degrees of clustering of windows supported by a lenslet relay and the image mapping associated with a free-space optical system, is described. A comparison of the optical beam properties at the device planes, including the spot size and power uniformity of the spot array, as well as the effects of clipping and misalignment for the different operating modes, is presented. In addition, the effects of beam clipping and misalignment for the different operating modes is presented. We show that microchannel free-space optical interconnects based on a window-clustering scheme significantly increase the connection density. A connection density of 2222 connections/cm(2) was achieved for this prototype system with 2 x 2 window clustering.


"Recommendations for uniform reporting of data following major trauma--the Utstein style" (as of July 17, 1999). An International Trauma Anaesthesia and Critical Care Society (ITACCS).
Basic and advanced care of trauma patients has always been an important aspect of prehospital and immediate in-hospital emergency medicine, involving a broad spectrum of disciplines, specialties and skills delivered through Emergency Medical Services Systems which, however, may differ significantly in structure, resources and operation. This complex background has, at least in part, hindered the development of a uniform pattern or set of criteria and definitions. This in turn has hitherto rendered data incompatible, with the consequence that such differing systems or protocols of care cannot be readily evaluated or compared with acceptable validity. Guided by previous consensus processes evolved by the ERC, the AHA and other International Organizations--represented in ILCOR--on 'Uniform reporting of data following out-of-hospital and in-hospital cardiac arrest--the Utstein style' an international working group of ITACCS has drafted a document, 'Recommendations for uniform reporting of data following major trauma--the Utstein style'. The reporting system is based on the following considerations: A structured reporting system based on an "Utstein style template" which would permit the compilation of data and statistics on major trauma care, facilitating and validating independent or comparative audit of performance and quality of care (and enable groups to challenge performance statistics which did not take account of all relevant information). The recommendations and template should encompass both out-of-hospital and in-hospital trauma care. The recommendations and template should further permit intra- and inter-system evaluation to improve the quality of delivered care and identification of the relative benefits of different systems and innovative initiatives. The template should facilitate studies setting out to improve epidemiological understanding of trauma; for example such studies might focus on the factors that determine survival. The document is structured along the lines of the original Utstein Style Guidelines publication on 'prehospital cardiac arrest'. It includes a glossary of terms used in the prehospital and early hospital phase and definitions, time points and intervals. The document uses an almost identical scheme for illustrating the different process time clocks--one for the patient, one for the dispatch centre, one for the ambulance and, finally, one for the hospital. For clarity, data should be reported as core data (i.e. always obtained) and optional data (obtained under specific circumstances). In contrast to the graphic approach used for the Utstein template for pre- or in-hospital cardiac arrest, respectively, the present template introduces, for the time being, at least, a number of terms and definitions and a semantic rather than a graphic report form. The document includes the following sections: The Section Introduction and background The Section on Trauma Data Structure Development: presents a general outline of the development of structured data using object-orientated modelling (which will be discussed in due course) and includes a set of explanatory illustrations. The Section on Terms and Definitions: outlines terms and definitions in trauma care, describing different types of trauma (blunt, penetrating, long bone, major/combined, multiple/polytrauma and predominant trauma). The Section on Factors relating to the circumstances of the injury describes the following items: cause of injury (e.g. type of injury (blunt or penetrating), burns, cold, crush, laceration, amputation, radiation, multiple, etc. Severity of Injury e.g. prehospital basic abbreviated injury score developed by the working group. The score contains anatomical and physiological disability data, with the anatomical scale ranging ordinally from 1. Head to 9. External; the physiological disability scale ranging ordinally from 0--unsurvivable. Mechanism of injury recording for transportation incidents etc. e.g. the type of impact, po


Space representation for eye movements is more contralateral in monkeys than in humans.
Contralateral hemispheric representation of sensory inputs (the right visual hemifield in the left hemisphere and vice versa) is a fundamental feature of primate sensorimotor organization, in particular the visuomotor system. However, many higher-order cognitive functions in humans show an asymmetric hemispheric lateralization--e.g., right brain specialization for spatial processing--necessitating a convergence of information from both hemifields. Electrophysiological studies in monkeys and functional imaging in humans have investigated space and action representations at different stages of visuospatial processing, but the transition from contralateral to unified global spatial encoding and the relationship between these encoding schemes and functional lateralization are not fully understood. Moreover, the integration of data across monkeys and humans and elucidation of interspecies homologies is hindered, because divergent findings may reflect actual species differences or arise from discrepancies in techniques and measured signals (electrophysiology vs. imaging). Here, we directly compared spatial cue and memory representations for action planning in monkeys and humans using event-related functional MRI during a working-memory oculomotor task. In monkeys, cue and memory-delay period activity in the frontal, parietal, and temporal regions was strongly contralateral. In putative human functional homologs, the contralaterality was significantly weaker, and the asymmetry between the hemispheres was stronger. These results suggest an inverse relationship between contralaterality and lateralization and elucidate similarities and differences in human and macaque cortical circuits subserving spatial awareness and oculomotor goal-directed actions.


Novel role of the renin-angiotensin system in preeclampsia superimposed on chronic hypertension and the effects of exercise in a mouse model.
Gestational hypertensive disorders, such as preeclampsia, affect 6% to 8% of all pregnancies in North America, and they are the leading cause of maternal mortality in industrialized countries, accounting for 16% of deaths. Women with hypertension have an increased risk (15% to 25%) of developing preeclampsia. Our aim was to investigate the mechanisms implicated in preeclampsia superimposed on chronic hypertension and in the protective effects of exercise in a mouse model. Female mice overexpressing human angiotensinogen and human renin were used as a model of preeclampsia superimposed on chronic hypertension. In the trained group, mothers were placed in cages with access to a wheel before mating, and they remained within these throughout gestation. Blood pressure was measured by telemetry. We found that angiotensin II type I receptor was increased, whereas the Mas receptor was decreased in the placenta and the aorta of pregnant sedentary transgenic mice. This would produce a decrease in angiotensin-(1-7) effects in favor of angiotensin II. Supporting the functional contribution of this modulation, we found that the prevention of most pathological features in trained transgenic mice was associated with a normalization of placental angiotensin II type 1 and Mas receptors and an increase in aortic Mas receptor. We also found reduced circulating and placental soluble Fms-like tyrosine kinase-1 in trained transgenic mice compared with sedentary mice. This study demonstrates that modulation of the renin-angiotensin system is a key mechanism in the development of preeclampsia superimposed on chronic hypertension, which can be altered by exercise training to prevent disease features in an animal model.


Effect of lamivudine in HIV-infected persons with prior exposure to zidovudine/didanosine or zidovudine/zalcitabine.
Nucleoside analog-based regimens remain an integral component of combination therapy for use in both antiretroviral treatment-naive and experienced HIV-infected patients. To further define treatment responses to new antiretroviral therapy in patients with long-term experience to dual nucleoside analog therapy (zidovudine [ZDV] plus didanosine [ddI] or ZDV plus zalcitabine [ddC]), 325 subjects derived from the AIDS Clinical Trials Group (ACTG) 175 trial were randomized to three different combination regimens: (1) continuation of ZDV + ddI or ZDV + ddC (continuation arm), (2) addition of 3TC to ZDV + ddI or ZDV + ddC (addition arm), or (3) a switch to ZDV + 3TC therapy (switch arm). Both the addition and switch arms sustained significantly greater short-term (baseline to week 4) mean CD4+ cell count increases compared with the continuation arm (+36, +28 versus -4 cells/mm3; p = 0.012) and long-term CD4+ cell count responses (baseline to weeks 40/48: +32, +19 versus -9 cells/mm3; p = 0.003). Superior short-term (baseline to week 8) mean decreases in plasma HIV RNA (p < 0.001) were achieved by both the addition and switch arms (0.53 log10 and 0.54 log10 copies/ml, respectively) compared with the continuation arm (0.13 copies/ml) whereas no differences in long-term virologic suppression were observed (p = 0.30). At week 48, no differences were observed in the proportions of subjects who had HIV RNA levels below 500 copies/mL: 18% of subjects in each treatment arm (3-way p = 1.0). Overall, the treatments were well tolerated and only nine subjects (3%) died or developed one or more AIDS-defining events. While this study confirms the intrinsic antiretroviral activity of 3TC, only modest marker changes and limited short-term viral suppression are seen with incremental addition of the drug. The current approach of using 3TC in maximally suppressive regimens is preferred.


The hypertrophic cardiomyopathy mutations R403Q and R663H increase the number of myosin heads available to interact with actin.
Hypertrophic cardiomyopathy (HCM) mutations in β-cardiac myosin and myosin binding protein-C (MyBP-C) lead to hypercontractility of the heart, an early hallmark of HCM. We show that hypercontractility caused by the HCM-causing mutation R663H cannot be explained by changes in fundamental myosin contractile parameters, much like the HCM-causing mutation R403Q. Using enzymatic assays with purified human β-cardiac myosin, we provide evidence that both mutations cause hypercontractility by increasing the number of functionally accessible myosin heads. We also demonstrate that the myosin mutation R403Q, but not R663H, ablates the binding of myosin with the C0-C7 fragment of MyBP-C. Furthermore, addition of C0-C7 decreases the wild-type myosin basal ATPase single turnover rate, while the mutants do not show a similar reduction. These data suggest that a primary mechanism of action for these mutations is to increase the number of myosin heads functionally available for interaction with actin, which could contribute to hypercontractility.


Effect of girdling at various positions of 'Huang Zhi Xiang' tea tree (Camellia sinensis) on the contents of catechins and starch in fresh leaf.
The contents of starch and catechins in the fresh leaf of 'Huang Zhi Xiang' Oolong tea trees girdled at the bottom, middle (on the big branches) and top (on the small branches) were determined. The study demonstrated that the starch contents from girdled trees were significantly higher (p<0.05) than that from non-girdled ones. Furthermore, the contents of (-)-epicatechin (EC), (-)-epigallocatechin (EGC), total catechins (TC) and simple catechins (SC) from girdled trees were significantly higher (p<0.05) than those from non-girdled ones. Especially, the contents of (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG) and catechin gallate (CG) from girdled at the middle were also significantly higher (p<0.05) than those from the non-girdled. The starch contents were negatively correlated with the contents of (-)-gallocatechin (GC), EC, SC, TC and EGC, while positively correlated with the contents of EGCG and CG in fresh shoots.


Athletes with a clinical rating of good and poor lumbopelvic stability have different kinematic variables during single leg squat and dip test.
To examine the kinematics of athletes with good and poor lumbopelvic stability (LPS) based on clinical rating criteria of single leg squat (SLS) and dip test (DT) The aim was to establish if good and poor LPS categorization is supported by differences in kinematic variables. Sixty-two recreational athletes had their LPS categorized using clinical rating criteria for SLS and DT as good, poor or neither good nor poor. Kinematic measures were examined in those with good (N = 8) or poor (N = 14) LPS and results compared to the rating criteria. Multiple clinical rating criteria for good and poor LPS groups were distinguished by kinematic measures. Smoothness of motion for both SLS and DT distinguished good and poor LPS. Minimal (good) or discernible movement (poor) out of the starting plane was confirmed with kinematic measures. For SLS these movements were: weight-bearing hip adduction, non-weightbearing hip abduction, pelvic rotation, and trunk sideflexion, and for DT: weightbearing hip adduction, non-weightbearing hip abduction and pelvic obliquity. Additionally, hip dissociation (SLS) distinguished good and poor LPS. Athletes with good and poor LPS have different kinematic measures in single leg squat and dip test. Multiple clinical rating criteria of LPS that distinguish good and poor stability were confirmed by kinematic measures.


Using a Critical Safety Behavior Scoring Tool for Just-in-Time Training for N95 Respirator Use.
Historically, health care workers (HCWs) have exhibited marginal adherence to proper N95 respirator use. During the COVID-19 pandemic, HCWs with little to no prior training on N95 respirator use are relying on N95s as their primary respiratory protection. There is a need for simple, effective, and easily implementable just-in-time training (JITT) interventions to improve N95 respirator-related safety behavior. This study investigated two JITT interventions. A pilot experimental pretest posttest study design was used to evaluate two training interventions for N95 respirator donning/doffing performance at a Midwestern hospital system. HCW participants were randomly assigned to an intervention: one used a 4-minute instructional video alone, while the other used the same video but added a video reflection intervention (participant watched and scored a video of their own performance). All performances were scored using a 10-point Critical Safety Behavior Scoring Tool (CSBST). Sixty-two HCWs participated (32 video alone, 30 video reflection). The two groups' CSBST scores were not significantly different at pretest. Averaged participant scores on the CSBST improved immediately following both interventions. Scores were significantly higher on the posttest for the reflective practice intervention (p<.05). Years of experience and frequency of N95 respirator use did not predict pre or post scores. We provide evidence to support the use of a time-efficient JITT intervention to improve HCW N95 respirator donning/doffing practices during the COVID-19 pandemic and beyond. Hospital safety professionals should consider this type of training for HCWs required to wear respiratory protection.


Information and participation preferences of dental patients.
Dutch dentists have a moral and legal obligation to inform their patients and involve them in the decision-making process. It is unclear, though, to what extent patients prefer information and involvement in decision-making. Therefore, the aim of this study was to determine levels of preference for information and participation in decision-making among emergency patients (n = 96) and regular patients (n = 245). It was hypothesized that female gender, higher education, younger age, and a monitoring coping style are positively associated with higher preferences for information and participation. The results demonstrated that emergency and regular patients have high preferences for information, but that their preferences for actual involvement are significantly lower. Only weak associations were found between the antecedent variables and patients' preferences. It is concluded that, in the study of the etiology of patients' preferences for information and participation, future research should incorporate factors such as dental anxiety and seriousness of the dental condition.


[Alternative nutrition and glutathione levels].
Low protein quality and quantity is reported to be a possible risk of alternative nutrition. Pulses contain 18-41% of methionine in relation to reference protein, moreover, its content in cereals is by one half lower. Therefore vegetarians and vegans may have an insufficient intake of sulphur-containing amino acids that may subsequently affect glutathione values (precursors of its synthesis). In groups of adults on an alternative diet--lactoovovegetarians (n = 47) and vegans (n = 44) aged 19-62 years with average duration on a vegetarian or vegan diet of 7.6 and 4.9 years, respectively, glutathione levels (GSH) were measured in erythrocytes (spectrophotometrically), as well as the activity of GSH-dependent enzymes. As nutritional control (n = 42) served an average sample of omnivores selected from a group of 489 examined, apparently healthy subjects of the same age range living in the same region. One to low protein intake (56% of RDA) exclusively of plant origin significantly lower levels of total proteins were observed in vegans with a 16% frequency of hypoproteinaemia (vs 0% in omnivores). In comparison to omnivores a significantly lower glutathione level was found (4.28 +/- 0.12 vs 4.84 +/- 0.14 mumol/g Hb, P < 0.01). Lactoovovegetarians because of their protein intake in adequate amounts with a 27% proportion of animal proteins (dairy products, eggs) consume a balanced mixture of amino acids, which is reflected in total protein levels similar to omnivores and significantly higher values of glutathione -5.26 +/- 0.12 mumol/g Hb, P < 0.05 (intake of glutathione in diet, higher consumption of fruit and vegetable in comparison to omnivores). A sufficient supply of glutathione as the substrate for enzymatic reactions of hydrogen peroxide or lipid hydroperoxide catabolism, as well as for detoxication of xenobiotics, was reflected in lactoovovegetarians in a significantly higher activity of glutathione-peroxidase and glutathione-S-transferase in erythrocytes. Low protein intake exclusively of plant origin, significantly lower protein levels with 16% frequency of hypoproteinaemia, significantly lower glutathione values in blood in comparison to omnivores and lactoovovegetarians confirm the risk of a vegan diet also in adult age.


Adnexal torsion. A clinical dilemma.
We retrospectively reviewed 33 cases of surgically managed adnexal torsion at the University of Tennessee Medical Center, Knoxville. Our interest was to observe any trends in age, parity, side involved, size, previous surgery, pathologic diagnosis or preoperative diagnosis. We found that there was no dominance in the side involved, as hypothesized by others. The most common previous surgery was bilateral tubal ligation, and the most common preoperative diagnosis was a pelvic mass. There is no absolute profile for the patient with adnexal torsion, and the clinician must be suspicious in all cases involving abdominal pain.


Rapid stimulatory effect of insulin on binding of glycolytic enzymes to cytoskeleton of C-6 glial cells, and the antagonistic action of calmodulin inhibitors.
Insulin was shown in our previous experiments to induce an increase in binding of glycolytic enzymes to muscle cytoskeleton. We show here the same stimulatory effect of insulin in C-6 glial cells in culture. In these cells, like in muscle, a short time of incubation with insulin (1-10 min) induced an increase in cytoskeleton bound phosphofructokinase and aldolase. This stimulatory effect of insulin could be prevented by treatment with calmodulin antagonists trifluoperazine, thioridazine or CGS 9343 B (a potent and selective inhibitor of calmodulin activity), which strongly suggests that calmodulin is involved in this action of insulin. Our previous experiments have shown that growth factors and Ca(2+) also induce a rapid, calmodulin-mediated stimulation of binding of glycolytic enzymes to cytoskeleton. The present and previous results suggest that the rapid binding of glycolytic enzymes to cytoskeleton, may be a general mechanism, in different cells, in signal transduction of insulin, growth factors and other Ca(2+) -mobilizing hormones. The accelerated cytoskeletal glycolysis will supply local ATP, which is required for the rapid cytoskeletal-membrane rearrangements following the binding of hormone to its receptor.


[Novel trends in pharmacotherapy of chronic obstructive pulmonary disease--prevention of exacerbations (focus on roflumilast)].
This report summarizes results of controlled clinical studies designed to evaluate the effectiveness and safety of roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor in patients with COPD and to identify the main groups of patients to whom prescription of this medication is indicated and results in reduction of repeated exacerbations. Generally speaking, roflumilast therapy appears justified for patients with symptoms of chronic bronchitis, severe or very severe bronchial obstruction (forced expiratory volume below 50%) and/or frequent exacerbations of the disease (= > 2/12 mo). Manifestations of symptomatic COPD (dyspnea, cough, expectoration, tolerance of physical exercises, etc.) are immaterial for taking decision to introduce roflumilast in combined therapy of COPD.


Response characteristics of esophageal balloon catheters handmade using latex and nonlatex materials.
The measurement of esophageal pressure allows for the calculation of several important and clinically useful parameters of respiratory mechanics. Esophageal pressure is often measured with balloon-tipped catheters. These catheters may be handmade from natural latex condoms and polyethylene tubing. Given the potential of natural latex to cause allergic reaction, it is important to determine whether esophageal catheter balloons can be fabricated, by hand, using nonlatex condoms as construction materials. To determine the static and dynamic response characteristics of esophageal balloon catheters handmade from latex and nonlatex materials, six esophageal catheter balloons were constructed from each of the following condom materials: natural latex, synthetic polyisoprene, and polyurethane (18 total). Static compliance and working volume range of each balloon catheter was obtained from their pressure-volume characteristics in water. The dynamic response of balloon catheters were measured via a pressure "step" test, from which a third-order underdamped transfer function was modeled. The dynamic ranges of balloon catheters were characterized by the frequencies corresponding to ±5% amplitude- and phase-distortion (fA5% and fφ5%). Balloon catheters handmade from polyurethane condoms displayed the smallest working volume range and lowest static balloon compliance. Despite this lower compliance, fA 5% and fφ5% were remarkably similar between all balloon materials. Our findings suggest that polyisoprene condoms are an ideal nonlatex construction material to use when fabricating esophageal catheter balloons by hand.


Targeting both rs12979860 and rs8099917 polymorphisms with a single-tube high-resolution melting assay for IL28b genotyping.
A rapid, duplex, high-resolution melting interleukin-28B gene (IL28B) genotyping assay, targeting both rs12979860 and rs8099917 polymorphisms, was developed and validated using 30 DNA samples from healthy volunteers. A linkage study on 300 healthy Singaporeans showed variable haplotypes. When the assay was applied to plasma DNA from 50 hepatitis C virus genotype-1 (HCV-1)-infected patients, five compound heterozygous types were detected.


Use of clinical and neuroimaging characteristics to distinguish temporal lobe herpes simplex encephalitis from its mimics.
We describe the spectrum of etiologies associated with temporal lobe (TL) encephalitis and identify clinical and radiologic features that distinguish herpes simplex encephalitis (HSE) from its mimics. We reviewed all adult cases of encephalitis with TL abnormalities on magnetic resonance imaging (MRI) from the California Encephalitis Project. We evaluated the association between specific clinical and MRI characteristics and HSE compared with other causes of TL encephalitis and used multivariate logistic modeling to identify radiologic predictors of HSE. Of 251 cases of TL encephalitis, 43% had an infectious etiology compared with 16% with a noninfectious etiology. Of infectious etiologies, herpes simplex virus was the most commonly identified agent (n = 60), followed by tuberculosis (n = 8) and varicella zoster virus (n = 7). Of noninfectious etiologies, more than half (n = 21) were due to autoimmune disease. Patients with HSE were older (56.8 vs 50.2 years; P = .012), more likely to be white (53% vs 35%; P = .013), more likely to present acutely (88% vs 64%; P = .001) and with a fever (80% vs 49%; P < .001), and less likely to present with a rash (2% vs 15%; P = .010). In a multivariate model, bilateral TL involvement (odds ratio [OR], 0.38; 95% confidence interval [CI], .18-.79; P = .010) and lesions outside the TL, insula, or cingulate (OR, 0.37; 95% CI, .18-.74; P = .005) were associated with lower odds of HSE. In addition to HSE, other infectious and noninfectious etiologies should be considered in the differential diagnosis for TL encephalitis, depending on the presentation. Specific clinical and imaging features may aid in distinguishing HSE from non-HSE causes of TL encephalitis.


Short-Term Findings From Testing EPIO, a Digital Self-Management Program for People Living With Chronic Pain: Randomized Controlled Trial.
Chronic pain conditions involve numerous physical and psychological challenges, and while psychosocial self-management interventions can be of benefit for people living with chronic pain, such in-person treatment is not always accessible. Digital self-management approaches could improve this disparity, potentially bolstering outreach and providing easy, relatively low-cost access to pain self-management interventions. This randomized controlled trial aimed to evaluate the short-term efficacy of EPIO (ie, inspired by the Greek goddess for the soothing of pain, Epione), a digital self-management intervention, for people living with chronic pain. Patients (N=266) were randomly assigned to either the EPIO intervention (n=132) or a care-as-usual control group (n=134). Outcome measures included pain interference (Brief Pain Inventory; primary outcome measure), anxiety and depression (Hospital Anxiety and Depression Scale), self-regulatory fatigue (Self-Regulatory Fatigue 18 scale), health-related quality of life (SF-36 Short Form Health Survey), pain catastrophizing (Pain Catastrophizing Scale), and pain acceptance (Chronic Pain Acceptance Questionnaire). Linear regression models used change scores as the dependent variables. The participants were primarily female (210/259, 81.1%), with a median age of 49 (range 22-78) years and a variety of pain conditions. Analyses (n=229) after 3 months revealed no statistically significant changes for the primary outcome of pain interference (P=.84), but significant reductions in the secondary outcomes of depression (mean difference -0.90; P=.03) and self-regulatory fatigue (mean difference -2.76; P=.008) in favor of the intervention group. No other statistically significant changes were observed at 3 months (all P>.05). Participants described EPIO as useful (ie, totally agree or agree; 95/109, 87.2%) and easy to use (101/109, 92.7%), with easily understandable exercises (106/109, 97.2%). Evidence-informed, user-centered digital pain self-management interventions such as EPIO may have the potential to effectively support self-management and improve psychological functioning in the form of reduced symptoms of depression and improved capacity to regulate thoughts, feelings, and behavior for people living with chronic pain. ClinicalTrials.gov NCT03705104; https://clinicaltrials.gov/ct2/show/NCT03705104.


[The role of surgery in acute epididymitis].
One third of the acute épididymitis (A.E.) admitted in the Military Hospital in Marseilles have been operated, i.e. 33 cases; out of them the last 12 cases have been systematically monitored by ultrasonography. Twice out of three times, clinical picture suggested a possible twisting that led to an emergency surgical exploration. Interest of ultrasonography of the scrotum is underlined as far as diagnosis is concerned but also in monitoring A.E. Indeed, despite medical treatment (antibiotics + anti-inflammatory drugs), it is possible that some A.E. are evolving either to abscess or to their "vascular" form; The ultimate form of the acute epididymo-orchitis is necrosis of the testis. This is due to, or amplified by, vascular compression linked up with edema. Surgical intervention has therefore to investigate by inguinal path the entire spermatic cord and the épididymis-testis system, and to apply the "decompression technique" requested.


What are the drugs of the future?
Are small molecules or biologics the drugs of the future? Small-molecule drugs have historically been the pillars of traditional medicine. However, recently, we seem to be amidst a scientific revolution with the rise of many FDA-approved biologic drugs. This opinion article looks at the current state of small molecules and biologics and assesses what the future holds for these two broad classes of drugs.


Cancer immunotherapy takes a multi-faceted approach to kick the immune system into gear.
Cancer accounts for about every fourth death in the United States, with approximately 1,500 people dying each day as a result of this disease. Despite some progress in the last decades, these numbers alone undoubtedly demonstrate the urgent need for new and more efficient treatments. Immunotherapy aims to activate an efficient immune response against tumors or even prevent cancers from occurring in the first place. It is a growing field currently flourishing with several successful trials, some of which have led to the recent approval of new anti-cancer drugs by the Food and Drug Administration (FDA). This review addresses the manifold strategies that immunotherapy has taken in the past and discusses the most recent achievements in the field.


Endosomes and Golgi vesicles in adsorptive and fluid phase endocytosis.
We studied with morphometric methods the endocytosis by pheochromocytoma cells of a conjugate of wheat germ agglutinin with ferritin (WGA-Ft) and of horseradish peroxidase (HRP). Quantitative studies indicated that WGA-Ft was cleared slowly from cell surfaces and that it was not recycled to the surface. Cells labeled with WGA-Ft for 15 min at room temperature were washed and incubated in medium containing HRP for 15 or 30 min at 37 degrees C. The greatest proportion of labeled vesicles and tubules contained only WGA-Ft (83.4% at 15 min and 85.3% at 30 min). A very small fraction of labeled vesicles and tubules contained only HRP (0.2% at 15 min and 0.9% at 30 min). Vesicles and tubules at the Golgi apparatus were labeled almost exclusively with WGA-Ft (97% at 15 min and 30 min); the rest had both labels. Most labeled lysosomes contained both labels (80.1% at 15 min and 80.8% at 30 min). Of the remainder more contained WGA-Ft alone (20% at 15 min and 10.9% at 30 min), then HRP alone (none at 15 min and 8.2% at 30 min). In contrast to the various and varying patterns of labeling with WGA-Ft and HRP of the other organelles studied, the vast majority of endosomes contained both markers (94.1% at 15 min and 100% at 30 min); the rest contained WGA-Ft only. These results demonstrate that endosomes are recipients of both fluid phase and adsorptive endocytosis markers; these findings are consistent with the hypothesis that endosomes mediate the sorting out and subsequent intracellular traffic of membrane bound and fluid phase markers. Cisterns of the Golgi apparatus did not contain WGA-Ft; in sharp contrast, when WGA-HRP was used, the cisterns of the Golgi apparatus consistently contained HRP.


Tooth shape reconstruction from dental CT images with the region-growing method.
The three-dimensional shape information of teeth provides useful information. However, obtaining accurate three-dimensional shapes of teeth is difficult without extracting them physically. In this study, we aimed to develop a method for automatically extracting accurate three-dimensional shapes of teeth from dental CT images. The proposed method includes pre-processing and region extraction. Pre-processing is a combination of image-processing techniques that enhances tooth regions. In the region-extraction process, the region-growing method is introduced for extracting a region of each tooth. Constraint conditions determined by considering the characteristics of the structure of teeth are introduced for accurate extraction. Finally, morphological image processing is applied for eliminating discontinuous points. We carried out an experiment in which the three-dimensional shapes of teeth were reconstructed from dental CT images. Quantitative evaluation was performed by measuring the three-dimensional spatial accordance rates between the region obtained by the proposed method and the manually extracted region. The proposed method was significantly more accurate than an existing method at the 5% level. The experimental results showed that the proposed method reconstructs the shapes of teeth with high precision. However, an unextracted region remained at the surface of the enamel. Solving this problem and improving the extraction accuracy are important topics for future work.


CD109 Overexpression in Pancreatic Cancer Identified by Cell-Surface Glycoprotein Capture.
The development of novel targeted cancer therapies and/or diagnostic tools is dependent upon an understanding of the differential expression of molecular targets between normal tissues and tumors. Many of these potential targets are cell-surface receptors; however, our knowledge of the cell-surface proteins upregulated in pancreatic tumors is limited, thus impeding the development of targeted therapies for pancreatic cancer. To develop new diagnostic and therapeutic tools to specifically target pancreatic tumors, we sought to identify cell-surface proteins that may serve as potential tumor-specfic targets. Membrane glycoproteins on the pancreatic cancer cell lines BxPC-3 were labeled with the bifunctional linker biocytin hydrazide. Following proteolytic digestion, biotinylated glycopeptides were captured with streptavidin-coupled beads then released by PNGaseF-mediated endoglycosidase cleavage and identified by liquid chromatography-tandem mass spectrometry (MS). A protein identified by the cell-surface glycoprotein capture procedure, CD109, was evaluated by western analysis of lysates of pancreatic cancer cell lines and by immunohistochemistry in sections of pancreatic ductal adenocarcinoma and non- neoplastic pancreatic tissues. MS/MS analysis of glycopeptides captured from BxPC-3 cells revealed 18 proteins predicted or known to be associated with the plasma membrane, including CD109, which has not been reported in pancreatic cancer. Western analysis of CD109 in lysates prepared from pancreatic cancer cell lines revealed it was expressed in 6 of 8 cell lines, with a high level of expression in BxPC-3, MIAPaCa-2, and Panc-1 cells. Immunohistochemical analyses of human pancreatic tissues indicate CD109 is significantly overexpressed in pancreatic tumors compared to normal pancreas. The selective capture of glycopeptides from the surface of pancreatic cancer cell lines can reveal novel cell-surface glycoproteins expressed in pancreatic ductal adenocarcinomas.


Cardiac Home Education and Support Trial (CHEST): a pilot study.
Coronary artery bypass graft (CABG) surgery is performed more frequently in individuals who are older and sicker than in previous years. Increased patient acuity and reduced hospital length of stays leave individuals ill prepared for their recovery. To test the feasibility of a peer support program and determine indicators of the effects of peer support on recovery outcomes of individuals following CABG surgery. A pre-post test pilot randomized clinical trial design enrolled men and women undergoing first-time nonemergency CABG surgery at a single site in Ontario. Patients were randomly assigned to either usual care or peer support. Patients allocated to usual care (n=50) received standard preoperative and postoperative education. Patients in the peer support group (n=45) received individualized education and support via telephone from trained cardiac surgery peer volunteers for eight weeks following hospital discharge. Most (93%) peer volunteers believed they were prepared for their role, with 98% of peer volunteers initiating calls within 72 h of the patient's discharge. Peer volunteers made an average of 12 calls, less than 30 min in duration over the eight-week recovery period. Patients were satisfied with their peer support (n=45, 98%). The intervention group reported statistical trends toward improved physical function (physical component score) (t [89]=-1.6; P=0.12) role function (t [93]=-1.9; P=0.06), less pain (t [93]=1.30; P=0.20) and improved cardiac rehabilitation enrollment (chi2=2.50, P=0.11). These preliminary results suggest that peer support may improve recovery outcomes following CABG. Data from the present pilot trial also indicate that a home-based peer support intervention is feasible and an adequately powered trial should be conducted.


Linguistic input, electronic media, and communication outcomes of toddlers with hearing loss.
The objectives of this study were to examine the quantity of adult words, adult-child conversational turns, and electronic media in the auditory environments of toddlers who are hard of hearing (HH) and to examine whether these factors contributed to variability in children's communication outcomes. Participants were 28 children with mild to severe hearing loss. Full-day recordings of children's auditory environments were collected within 6 months of their second birthdays by using Language ENvironment Analysis technology. The system analyzes full-day acoustic recordings, yielding estimates of the quantity of adult words, conversational turns, and electronic media exposure in the recordings. Children's communication outcomes were assessed via the receptive and expressive scales of the Mullen Scales of Early Learning at 2 years of age and the Comprehensive Assessment of Spoken Language at 3 years of age. On average, the HH toddlers were exposed to approximately 1400 adult words per hour and participated in approximately 60 conversational turns per hour. An average of 8% of each recording was classified as electronic media. However, there was considerable within-group variability on all three measures. Frequency of conversational turns, but not adult words, was positively associated with children's communication outcomes at 2 and 3 years of age. Amount of electronic media exposure was negatively associated with 2-year-old receptive language abilities; however, regression results indicate that the relationship was fully mediated by the quantity of conversational turns. HH toddlers who were engaged in more conversational turns demonstrated stronger linguistic outcomes than HH toddlers who were engaged in fewer conversational turns. The frequency of these interactions was found to be decreased in households with high rates of electronic media exposure. Optimal language-learning environments for HH toddlers include frequent linguistic interactions between parents and children. To support this goal, parents should be encouraged to reduce their children's exposure to electronic media.


Chemical modifications of PhTX-I myotoxin from Porthidium hyoprora snake venom: effects on structural, enzymatic, and pharmacological properties.
We recently described the isolation of a basic PLA2 (PhTX-I) from Porthidium hyoprora snake venom. This toxin exhibits high catalytic activity, induces in vivo myotoxicity, moderates footpad edema, and causes in vitro neuromuscular blockade. Here, we describe the chemical modifications of specific amino acid residues (His, Tyr, Lys, and Trp), performed in PhTX-I, to study their effects on the structural, enzymatic, and pharmacological properties of this myotoxin. After chemical treatment, a single His, 4 Tyr, 7 Lys, and one Trp residues were modified. The secondary structure of the protein remained unchanged as measured by circular dichroism; however other results indicated the critical role played by Lys and Tyr residues in myotoxic, neurotoxic activities and mainly in the cytotoxicity displayed by PhTX-I. His residue and therefore catalytic activity of PhTX-I are relevant for edematogenic, neurotoxic, and myotoxic effects, but not for its cytotoxic activity. This dissociation observed between enzymatic activity and some pharmacological effects suggests that other molecular regions distinct from the catalytic site may also play a role in the toxic activities exerted by this myotoxin. Our observations supported the hypothesis that both the catalytic sites as the hypothetical pharmacological sites are relevant to the pharmacological profile of PhTX-I.


Maintenance and regulation of asymmetric phospholipid distribution in human erythrocyte membranes: implications for erythrocyte functions.
The article summarizes new insights into the molecular mechanisms for the maintenance and regulation of the asymmetric distribution of phospholipids in human erythrocyte membranes. We focus on phosphatidylserine, which is primarily found in the inner leaflet of the membrane lipid bilayer under low Ca conditions (<1 μmol/l) and is exposed to the outer leaflet under elevated Ca concentrations (>1 μmol/l), when cells become senescent. Clarification of the molecular basis of phosphatidylserine flipping and scrambling is important for addressing long-standing questions regarding phosphatidylserine functions. ATP11C, a P-IV ATPase, has been identified as a major flippase in analyses of patient erythrocytes with a 90% reduction in flippase activity. Phospholipid scramblase 1 (PLSCR1) has been defined as a Ca-activated scramblase that is completely suppressed by membrane cholesterol under low Ca concentrations. For survival, phosphatidylserine surface exposure is prevented by cholesterol-mediated suppression of PLSCR1 under low Ca concentrations, irrespective of flipping by ATP11C. In senescent erythrocytes, PLSCR1 is activated by elevated Ca, resulting in phosphatidylserine exposure, allowing macrophage phagocytosis. These recent molecular findings establish the importance of the maintenance and regulation of phosphatidylserine distribution for both the survival and death of human erythrocytes.


Design of the WHIP-PD study: a phase II, twelve-month, dual-site, randomized controlled trial evaluating the effects of a cognitive-behavioral approach for promoting enhanced walking activity using mobile health technology in people with Parkinson-disease.
Parkinson disease (PD) is a debilitating and chronic neurodegenerative disease resulting in ambulation difficulties. Natural walking activity often declines early in disease progression despite the relative stability of motor impairments. In this study, we propose a paradigm shift with a "connected behavioral approach" that targets real-world walking using cognitive-behavioral training and mobile health (mHealth) technology. The Walking and mHealth to Increase Participation in Parkinson Disease (WHIP-PD) study is a twelve-month, dual site, two-arm, randomized controlled trial recruiting 148 participants with early to mid-stage PD. Participants will be randomly assigned to connected behavioral or active control conditions. Both conditions will include a customized program of goal-oriented walking, walking-enhancing strengthening exercises, and eight in-person visits with a physical therapist. Participants in the connected behavioral condition also will (1) receive cognitive-behavioral training to promote self-efficacy for routine walking behavior and (2) use a mHealth software application to manage their program and communicate remotely with their physical therapist. Active control participants will receive no cognitive-behavioral training and manage their program on paper. Evaluations will occur at baseline, three-, six-, and twelve-months and include walking assessments, self-efficacy questionnaires, and seven days of activity monitoring. Primary outcomes will include the change between baseline and twelve months in overall amount of walking activity (mean number of steps per day) and amount of moderate intensity walking activity (mean number of minutes per day in which > 100 steps were accumulated). Secondary outcomes will include change in walking capacity as measured by the six-minute walk test and ten-meter walk test. We also will examine if self-efficacy mediates change in amount of walking activity and if change in amount of walking activity mediates change in walking capacity. We expect this study to show the connected behavioral approach will be more effective than the active control condition in increasing the amount and intensity of real-world walking activity and improving walking capacity. Determining effective physical activity interventions for persons with PD is important for preserving mobility and essential for maintaining quality of life. Clinical trials registration NCT03517371, May 7, 2018. ClinicalTrials.gov: NCT03517371. Date of registration: May 7, 2018. Protocol version: Original.


Prostaglandin E2 metabolite levels during diabetic ketoacidosis.
Insulin therapy was withdrawn from 15 well-controlled type I diabetic subjects for no longer than 18 h to examine the sequence with which 13,14-dihydro-15-keto-PGE2 (PGE-m), glucagon, norepinephrine, and epinephrine increased in circulating blood in diabetic subjects becoming ketoacidotic. Fourteen of 15 patients had increments in PGE-m; 12/12, 12/15, and 13/15 had increments in glucagon, norepinephrine, and epinephrine, respectively. Six of the 15 patients developed mild diabetic ketoacidosis (DKA) by 12-18 h; all had nonmeasurable C-peptide levels. This DKA group had significantly greater increments of PGE-m (835 +/- 130 versus 276 +/- 111 pg/ml, mean +/- SEM, P less than 0.01) but not glucagon, norepinephrine, or epinephrine compared with the 9 non-DKA patients. In the DKA group, there were significant PGE-m and glucagon increments in the circulation by 3 h, significant norepinephrine increments by 9 h, and epinephrine increments in 5/6 patients by 12 h (not statistically significant) of insulin withdrawal. These studies document that (1) PGE-m accumulates in the circulation during DKA, (2) PGE-m and glucagon increase before catecholamines, and (3) PGE-m, glucagon, and catecholamine levels promptly return to normal levels when insulin therapy is reinstituted. It is suggested that elevated PGE-m levels early in the onset of DKA may represent a host-defense mechanism.


High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice.
Dietary fibers are mainly fermented by the gut microbiota, but their roles in colorectal cancer (CRC) are largely unclear. Here, we investigated the associations of different fibers with colorectal tumorigenesis in mice. Apcmin/+ mice and C57BL/6 mice with azoxymethane (AOM) injection were used as CRC mouse models. Mice were fed with mixed high-fiber diet (20% soluble fiber and 20% insoluble fiber), high-inulin diet, high-guar gum diet, high-cellulose diet, or diets with different inulin dose. Germ-free mice were used for validation. Fecal microbiota and metabolites were profiled by shotgun metagenomic sequencing and liquid chromatography-mass spectrometry, respectively. Mixed high-fiber diet promoted colorectal tumorigenesis with increased tumor number and tumor load in AOM-treated and Apcmin/+ mice. Antibiotics use abolished the pro-tumorigenic effect of mixed high-fiber diet, while transplanting stools from mice fed with mixed high-fiber diet accelerated tumor growth in AOM-treated germ-free mice. We therefore characterized the contribution of soluble and insoluble fiber in CRC separately. Our results revealed that soluble fiber inulin or guar gum, but not insoluble fiber cellulose, promoted colorectal tumorigenesis in AOM-treated and Apcmin/+ mice. Soluble fiber induced gut dysbiosis with Bacteroides uniformis enrichment and Bifidobacterium pseudolongum depletion, accompanied by increased fecal butyrate and serum bile acids and decreased inosine. We also identified a positive correlation between inulin dosage and colorectal tumorigenesis. Moreover, transplanting stools from mice fed with high-inulin diet increased colonic cell proliferation and oncogene expressions in germ-free mice. High-dose soluble but not insoluble fiber potentiates colorectal tumorigenesis in a dose-dependent manner by dysregulating gut microbiota and metabolites in mice.


In Situ Monitoring of Transiently Formed Molecular Chaperone Assemblies in Bacteria, Yeast, and Human Cells.
J-domain proteins (JDPs) form the largest and the most diverse co-chaperone family in eukaryotic cells. Recent findings show that specific members of the JDP family could form transient heterocomplexes in eukaryotes to fine-tune substrate selection for the 70 kDa heat shock protein (Hsp70) chaperone-based protein disaggregases. The JDP complexes target acute/chronic stress induced aggregated proteins and presumably help assemble the disaggregases by recruiting multiple Hsp70s to the surface of protein aggregates. The extent of the protein quality control (PQC) network formed by these physically interacting JDPs remains largely uncharacterized in vivo. Here, we describe a microscopy-based in situ protein interaction assay named the proximity ligation assay (PLA), which is able to robustly capture these transiently formed chaperone complexes in distinct cellular compartments of eukaryotic cells. Our work expands the employment of PLA from human cells to yeast (Saccharomyces cerevisiae) and bacteria (Escherichia coli), thus rendering an important tool to monitor the dynamics of transiently formed protein assemblies in both prokaryotic and eukaryotic cells.


Analysis of Prefrontal Single-Channel EEG Data for Portable Auditory ERP-Based Brain-Computer Interfaces.
An electroencephalogram (EEG)-based brain-computer interface (BCI) is a tool to non-invasively control computers by translating the electrical activity of the brain. This technology has the potential to provide patients who have severe generalized myopathy, such as those suffering from amyotrophic lateral sclerosis (ALS), with the ability to communicate. Recently, auditory oddball paradigms have been developed to implement more practical event-related potential (ERP)-based BCIs because they can operate without ocular activities. These paradigms generally make use of clinical (over 16-channel) EEG devices and natural sound stimuli to maintain the user's motivation during the BCI operation; however, most ALS patients who have taken part in auditory ERP-based BCIs tend to complain about the following factors: (i) total device cost and (ii) setup time. The development of a portable auditory ERP-based BCI could overcome considerable obstacles that prevent the use of this technology in communication in everyday life. To address this issue, we analyzed prefrontal single-channel EEG data acquired from a consumer-grade single-channel EEG device using a natural sound-based auditory oddball paradigm. In our experiments, EEG data was gathered from nine healthy subjects and one ALS patient. The performance of auditory ERP-based BCI was quantified under an offline condition and two online conditions. The offline analysis indicated that our paradigm maintained a high level of detection accuracy (%) and ITR (bits/min) across all subjects through a cross-validation procedure (for five commands: 70.0 ± 16.1 and 1.29 ± 0.93, for four commands: 73.8 ± 14.2 and 1.16 ± 0.78, for three commands: 78.7 ± 11.8 and 0.95 ± 0.61, and for two commands: 85.7 ± 8.6 and 0.63 ± 0.38). Furthermore, the first online analysis demonstrated that our paradigm also achieved high performance for new data in an online data acquisition stream (for three commands: 80.0 ± 19.4 and 1.16 ± 0.83). The second online analysis measured online performances on the different day of offline and first online analyses on a different day (for three commands: 62.5 ± 14.3 and 0.43 ± 0.36). These results indicate that prefrontal single-channel EEGs have the potential to contribute to the development of a user-friendly portable auditory ERP-based BCI.


A hypomorphic mutation of the gamma-1 adaptin gene (Ap1g1) causes inner ear, retina, thyroid, and testes abnormalities in mice.
Adaptor protein (AP) complexes function in the intracellular sorting and vesicular transport of membrane proteins. The clathrin-associated AP-1 complex functions at the trans-Golgi network and endosomes, and some forms of this complex are thought to mediate the sorting of proteins in plasma membranes of polarized epithelial cells. A null mutation of the mouse Ap1g1 gene, which encodes the gamma-1 subunit of the AP-1 complex, causes embryonic lethality when homozygous, indicating its critical importance in early development but precluding studies of its possible roles during later stages. Here, we describe our analyses of a new spontaneous mutation of Ap1g1 named "figure eight" (symbol fgt) and show that it is an in-frame deletion of 6 bp, which results in the elimination of two amino acids of the encoded protein. In contrast to Ap1g1 (-/-) null mice, mice homozygous for the recessive fgt mutation are viable with adult survival similar to controls. Although Ap1g1 is ubiquitously expressed, the phenotype of Ap1g1 (fgt) mutant mice is primarily restricted to abnormalities in sensory epithelial cells of the inner ear, pigmented epithelial cells of the retina, follicular epithelial cells of the thyroid gland, and the germinal epithelium of the testis, suggesting that impaired AP-1 sorting and targeting of membrane proteins in these polarized cells may underlie the observed pathologies. Ap1g1 (fgt) mutant mice provide a new animal model to study the in vivo roles of gamma-1 adaptin and the AP-1 complex throughout development and to investigate factors that underlie its associated phenotypic abnormalities.


De novo transcriptome analysis of the excretory tubules of Carausius morosus (Phasmatodea) and possible functions of the midgut 'appendices'.
The Malpighian tubules are the insect excretory organs, responsible for ion and water homeostasis and elimination of nitrogenous wastes. Post-genomic assays suggest they also metabolize and detoxify xenobiotic compounds and have antimicrobial properties. The Phasmatodea have an additional, unique set of excretory organs referred to predominantly as midgut appendices. Their function and how it compares to phasmid and other insect Malpighian tubules is unknown. Hypotheses include carbonic anhydrase activity, calcium and metal cation sequestration, and xenobiotic transport. This work presents the first comparative transcriptomic analysis of the Phasmatodean excretory organs, using the model insect Carausius morosus. I produced de novo transcriptomes of the midgut appendices, midgut wall, and Malpighian tubules, and looked for differentially expressed genes associated with putative organ functions. The appendices differentially and highly express lipid transport and metabolism proteins, and the biomineralization gene otopetrin. The Malpighian tubules differentially and highly express acid phosphatases and multiple transporter types, while appendices express fat-soluble vitamin and peptide transporters. Many defense proteins such as multidrug resistance proteins, ABC transporters, cytochrome P450's, and glutathione-S-transferases were differentially expressed in specific excretory organs. I hypothesize that the appendices and Malpighian tubules both have defensive / xenobiotic metabolism functions, but each likely target different substrates. Phasmid Malpighian tubules excrete as in other insects, while the appendices may predominantly regulate amino acids, fats, and fat-soluble compounds. Lipid metabolism in insects is poorly understood, and the Phasmatodea may thus serve as a model for studying this further.


Thirst following water deprivation in humans.
The effect of 24-h water deprivation and subsequent drinking on systemic fluid balance and subjective sensations has been determined in human beings. The deprivation caused significant intracellular and extracellular depletions, thirst, and a dry unpleasant tasting mouth. During rehydration, subjects drank 65% of their total intake within 2.5 min. The marked decrease in drinking rate thereafter, and the alleviation of thirst, occurred before plasma dilution had become significant. This attenuation of drinking was subjectively attributed to stomach fullness. Presystemic factors may therefore be important for drinking termination in humans. Within 20 min systemic deficits were removed, but intermittent drinking continued at a low rate, reportedly to alleviate unpleasant oral sensations, Following rehydration, the concentrated urine of hydropenia had disappeared. However, the excretion of solute-free water varied between subjects. Plasma renin activity was significantly elevated by water deprivation, while after rehydration this activity had decreased to levels not significantly different from predeprivation values.


[The establishment of the presence of sperm in stains by an agar gel electrophoretic method].
Comparative investigation of seminal stains and other secretions from human body and blood as well as objects of plant origin by gel electrophoresis using alkaline values of pH buffer solutions and subsequent enzymography for acid phosphatase made it possible to develop optimal conditions for detection of seminal presence in stains. Good preservation of seminal acid phosphatase in stains during several years is shown.


[Parameters of heart rate variability during bicycle ergometry test].
Short-term (5 min) heart rate variability (HRV) was studied before and during submaximal bicycle exercise tests in 27 patients with ischemic heart disease, 23 patients with hypertension and 9 healthy subjects. Low-frequency (0.04 to 0.15 Hz) and high-frequency (0.15 to 0.40 Hz) power components of HRV were significantly decreased during submaximal exercise. The level of load at which abrupt decrease of low-frequency components below 40 ms(2) occurred possibly reflected individual exercise tolerance. Episodes of myocardial ischemia were associated with pronounced decreases of low - frequency HRV components.


Robotic-assisted Navigation Bronchoscopy: A Meta-Analysis of Diagnostic Yield and Complications.
Robotic-assisted navigation bronchoscopy (RANB) is a novel method to biopsy lung nodules, with initial reports demonstrating excellent accuracy. We aimed to evaluate pooled estimates of diagnostic yields and complication rates with RANB by performing a meta-analysis of the available literature. We searched 3 databases, including PubMed, EmBase, and Web of Science. The resulting abstracts were reviewed by 2 investigators. Analyses were performed using random effects models, and diagnostic yield and complication rates were estimated after the Freeman-Tukey transformation. A total of 23 articles, comprising 1409 patients and 1541 nodules, were included in the final analysis. Mean ages ranged from 63.2 to 69.3 years. The average size of the nodules ranged between 5.9 and 25.0 mm. Most patients (54.0% to 92.0%) had a current or prior smoking history in studies that reported them (n=8). The pooled diagnostic yield was 81.9% (12 studies, 838 nodules, 95% CI: 83.4%-91.0%), and the pooled sensitivity for malignancy was 87.6% (8 studies, 699 nodules, 95% CI: 81.3%-89.5%). The pooled incidence of pneumothorax rates was 0.60% (95% CI: 0.11%-1.35%). The pooled incidence of major bleeding was <0.01%. Diagnostic yield for patients with pulmonary nodules undergoing RANB is high, though may be impacted by the prevalence of malignancy, participant selection, and publication bias. Complication rates, including pneumothoraces and bleeding rates, appear low across all studies. If RANB is available, clinicians should consider utilizing this platform to biopsy pulmonary nodules.


The Possible Impact of Obesity on Androgen, Progesterone and Estrogen Receptors (ERα and ERβ) Gene Expression in Breast Cancer Patients.
Obesity has been associated with increased mortality from hormone dependant cancers such as breast cancer which is the most prevalent cancer in women. The link between obesity and breast cancer can be attributed to excess estrogen produced through aromatization in adipose tissue. The role of steroid hormone receptors in breast cancer development is well studied but how obesity can affect the expression pattern of steroid hormones in patients with different grades of breast cancer was the aim of this study. In this case-control study, 70 women with breast cancer participated with different grades of obesity (36 none obese, BMI < 25 kg/m(2) and 34 obese, BMI ≥ 25 kg/m(2)). The mean age of participants was 44.53 ± 1.79 yr (21-70 yr). The serum level of estrogen, progesterone and androgen determined by ELISA. Following quantitative expression of steroid hormone receptors mRNA in tumor tissues evaluated by Real-time PCR. Patients with previous history of radiotherapy or chemotherapy were excluded. SPSS 16 was used for data analysis and P < 0.05 considered statistically significant. The difference in ERα, ERβ and PR mRNA level between normal and obese patients was significant (P < 0.001). In addition, the expression of AR mRNA was found to be higher than other steroid receptors. There was no significant relation between ERβ gene expression in two groups (P = 0.68). We observed a significant relationship between ERα and AR mRNA with tumor stage and tumor grade, respectively (P = 0.023, P = 0.015). According to the obtained results, it is speculated that obesity could paly a significant role in estrogen receptors gene expression and also could affect progression and proliferation of breast cancer cells.


Comorbidity and subgroups in childhood autism.
The objective of this study was to identify clinical subgroups in children with childhood autism and to examine comorbidity in each subgroup. The study was based on medical records of 30 inpatients referred to a specialist ward for children with pervasive developmental disorders. Eighteen consecutive patients with an IQ above 50 and fulfilling research criteria for childhood autism were grouped in accordance with the Wing's social subgroups of autism (aloof, passive, and active but odd). Comorbidity, in terms of deficits in attention, motor control, visuo-motor and visuo-spatial function, as well as epilepsy, was described in each of the three groups. The aloof and passive groups produced a pure autistic triad of deficits, while the active but odd group was characterized by strong comorbidity.


Quantifying Sweet Taste Liker Phenotypes: Time for Some Consistency in the Classification Criteria.
Taste hedonics is a well-documented driver of food consumption. The role of sweetness in directing ingestive behavior is largely rooted in biology. One can then intuit that individual differences in sweet-liking may constitute an indicator of variations in the susceptibility to diet-related health outcomes. Despite half a century of research on sweet-liking, the best method to identify the distinct responses to sweet taste is still debated. To help resolve this issue, liking and intensity ratings for eight sucrose solutions ranging from 0 to 1 M were collected from 148 young adults (29% men). Hierarchical cluster analysis (HCA) revealed three response patterns: a sweet-liker (SL) phenotype characterized by a rise in liking as concentration increased, an inverted U-shaped phenotype with maximum liking at 0.25 M, and a sweet-disliker (SD) phenotype characterized by a decline in liking as a function of concentration. Based on sensitivity and specificity analyses, present data suggest the clearest discrimination between phenotypes is seen with 1.0 M sucrose, where a liking rating between -15 and +15 on a -50/+50 scale reliably distinguished individuals with an inverted U-shaped response from the SLs and the SDs. If the efficacy of this approach is confirmed in other populations, the discrimination criteria identified here can serve as the basis for a standard method for classifying sweet taste liker phenotypes in adults.


Human Neural Stem Cell Therapy for Chronic Ischemic Stroke: Charting Progress from Laboratory to Patients.
Chronic disability after stroke represents a major unmet neurologic need. ReNeuron's development of a human neural stem cell (hNSC) therapy for chronic disability after stroke is progressing through early clinical studies. A Phase I trial has recently been published, showing no safety concerns and some promising signs of efficacy. A single-arm Phase II multicenter trial in patients with stable upper-limb paresis has recently completed recruitment. The hNSCs administrated are from a manufactured, conditionally immortalized hNSC line (ReNeuron's CTX0E03 or CTX), generated with c-mycERTAM technology. This technology has enabled CTX to be manufactured at large scale under cGMP conditions, ensuring sufficient supply to meets the demands of research, clinical development, and, eventually, the market. CTX has key pro-angiogenic, pro-neurogenic, and immunomodulatory characteristics that are mechanistically important in functional recovery poststroke. This review covers the progress of CTX cell therapy from its laboratory origins to the clinic, concluding with a look into the late stage clinical future.


Short cardiac iodine-123-metaiodobenzylguanidine imaging protocol in heart failure.
For assessment of cardiac sympathetic nervous activity, the conventional protocol for iodine-123-metaiodobenzylguanidine ((123)I-MIBG) imaging requires several hours. To establish whether it is possible to shorten the conventional (123)I-MIBG imaging protocol, anterior planar imaging was performed in 42 heart failure (HF) patients at 5, 15 and 180 min. The washout rate of (123)I-MIBG from 5 to 15 min (WR5-15 min) was calculated as a novel index. WR5-15 min closely correlated with the conventional washout rate and inversely correlated with the heart to mediastinum ratio. Univariate Cox analysis revealed that rapid WR5-15 min, augmented plasma B-type natriuretic peptide level, and decreased left ventricular ejection fraction (LVEF) were predictors for cardiac events. Multivariate analysis showed WR5-15 min and LVEF were independent predictors. The cardiac event rate was markedly higher (73%) in patients when both WR5-15 min and LVEF were abnormal. WR5-15 min obtained from anterior planar imaging is useful for evaluating the severity of HF and clinical outcome, and may shorten the cardiac (123)I-MIBG scintigraphy protocol.


Synthetic cannabinoid use in psychiatric patients and relationship to hospitalisation: A retrospective electronic case register study.
Cannabis use has been associated with psychosis and with poor outcome in patients with mental illness. Synthetic cannabinoids (SCs) have been suggested to pose an even greater risk to mental health, but the effect on clinical outcome has not been directly measured. In this study, we aimed to investigate the demographics and hospitalisation of psychiatric patients who were SC users. We searched the Biomedical Research Centre Clinical Record Interactive Search register for SC users and age- and sex-matched SC non-users who had been psychiatric patients under the South London and Maudsley NHS Trust. We recorded diagnosis, homelessness, cannabis use and the total number of days admitted as an inpatient to secondary and tertiary mental-health services. We identified 635 SC users and 635 age- and sex-matched SC non-users. SC users were significantly more likely to be homeless (χ2=138.0; p<0.0001) and to use cannabis (χ2=257.3; p<0.0001) than SC non-users. SC users had significantly more inpatient days after their first recorded use of SCs than controls (M (SD)=85.5 (199.7) vs. 25.4 (92.32); p<0.0001). Post hoc tests revealed that SC non-users who used cannabis had fewer inpatient days than SC users (p<0.0001), and that non-users of both SC and cannabis had fewer inpatient days than SC non-using cannabis users (p=0.02). SC use may lead to an increase in the number of days spent in hospital in patients with psychiatric illness. This highlights the need for clinicians to ask specifically about SC use.


The role of anaesthetists in the Darwin response to the Bali bombing.
The bombing of nightclubs in Bali on the night of October 12, 2002 was one of the worst peacetime disasters affecting Australians. This paper examines the unique role of anaesthetists in helping manage the victims, with the main emphasis on events in Darwin. Anaesthetists were involved in the multiple stages of patient care; from the hospital in Bali, evacuation to Darwin, resuscitation and onward evacuation to burns units around Australia as well as definitive surgical management. We discuss the role of anaesthetists in disaster management.


Axillary lymph node dissection on the run?
The standard approach of performing a completion axillary lymph node dissection (cALND) after a positive sentinel node for breast cancer patients is no longer generally accepted. This study applied the criterion of a 27% risk of having residual positive lymph nodes calculated by the MD Anderson nomogram to perform a cALND. This 27% cut-off is based on the number of positive non-sentinels in the Z0011 trial. A cohort of 166 cN0, sentinel positive breast cancer patients was used to validate the MD Anderson nomogram. ROC (Receiver Operating Characteristic) analysis shows an AUC (Area Under the Curve) of 0.76 and an optimal cut-off at 34% risk of positive non- SLNs (sensitivity 86%, specificity 57%). The 27% cut-off has a sensitivity of 88% and a specificity of 41% to detect positive non-sentinels. In a second cohort (N= 114) the 27% cut-off criterion was prospectively applied and appeared to be practice changing. Although we take minimal risk to leave disease behind (2/166 patients >3 positive nodes), 30.7 % in the first cohort and 54.4 % of the patients in the second cohort could be spared a cALND. The Z0011 criteria would have had more impact, omitting 90% of the cALND, but leaves more disease behind. The impact of leaving disease behind on survival remains unanswered but is awaited by long term follow up of large prospective cohort studies.


Preoperative Nomograms for Predicting Renal Function at 1 Year After Partial Nephrectomy.
Partial nephrectomy (PN) reduces the risk of postoperative chronic renal insufficiency (CRI). However, some patients still develop CRI after PN, and may eventually require dialysis. Being able to predict renal function before PN helps in counseling patients and managing expectations. We aimed to construct nomograms that predict estimated glomerular filtration rates (eGFRs), defined by the modification of diet in renal disease (MDRD) and the chronic kidney disease epidemiology collaboration (CKD-EPI) formulae, at 1 year after PN, using only preoperative covariates as predictors. We identified patients who underwent PN in our institution between 2004 and 2016, with known postoperative serum creatinine levels at 1 year. The preoperative covariates included patients' demographics, chronic comorbid conditions, tumor characteristics, and preoperative renal status. The endpoints were eGFRs at 1 year after PN, calculated using the MDRD and the CKD-EPI formulae. We first identified preoperative covariates with significant associations with the endpoints by Pearson correlation and independent samples t-test. Suitable covariates were then included in two multivariate linear regression models, for constructing and internally validating two nomograms. 461 patients were eligible for analysis. The percentage of patients with eGFR below 60 mL/min/1.73 m2 increased from 25% before PN to 35% at 1 year after PN. We included age, gender, African American race, body mass index, preoperative creatinine level, ipsilateral renal volume, solitary kidney status, tumor diameter, hypertension, diabetes, ischemic heart disease, and previous stroke in the multivariate linear regression models for nomogram construction. Internal validation showed bootstrap-corrected coefficients of determination of 0.61 and 0.70, for predicting eGFRs defined by the MDRD and CKD-EPI formulae, respectively. We constructed and internally validated two nomograms to predict eGFRs at 1 year after PN, using only preoperative covariates as predictors.


Functional characterization of a UDP-glucose:flavonoid 3-O-glucosyltransferase from the seed coat of black soybean (Glycine max (L.) Merr.).
The seed coats of black soybean (Glycine max (L.) Merr.) accumulate red (cyanidin-), blue (delphinidin-), purple (petunidin-), and orange (pelargonidin-based) anthocyanins almost exclusively as 3-O-glucosides; however, the responsible enzyme has not been identified. In this study, the full-length cDNA which encodes the enzyme that catalyzes the final step in anthocyanin biosynthesis, namely UDP-glucose:flavonoid 3-O-glucosyltransferase (UGT78K1), was isolated from the seed coat tissue of black soybean using rapid amplification of cDNA ends (RACE). Of the 28 flavonoid substrates tested, the purified recombinant protein glucosylated only anthocyanidins and flavonols, and demonstrated strict 3-OH regiospecificity. Galactose could also be transferred with relatively low activity to the 3-position of cyanidin or delphinidin in vitro. These findings are consistent with previous reports of mainly 3-O-glucosylated and minor amounts of 3-O-galactosylated anthocyanins in the seed coat of black soybean. The recombinant enzyme exhibited pronounced substrate inhibition by cyanidin at 100 microM acceptor concentration. Transfer of UGT78K1 into the Arabidopsis T-DNA mutant (ugt78d2) deficient in anthocyanidin and flavonol 3-O-glucosyltransferase activity, restored the accumulation of anthocyanins and flavonols, suggesting the in vivo function of the enzyme as a flavonoid 3-O-glucosyltransferase. Genomic and phylogenetic analyses suggest the existence of three additional soybean sequences with high similarity to UGT78K1. RT-PCR confirmed the co-expression of one of these genes (Glyma08g07130) with UGT78K1 in the seed coat of black soybean, suggesting possible functional redundancies in anthocyanin biosynthesis in this tissue.


Modified insulator semiconductor electrode with functionalized nanoparticles for Proteus mirabilis bacteria biosensor development.
The development of enzymatic sensors for biological purposes such as biomedicine, pharmacy, food industry, and environmental toxicity requires the purification step of the enzyme. To prevent the loss of the enzyme activity, a new strategy is held in order to immobilize the bacteria. It will constitute the biological sensing element leading to a high operational stability and multiple adaptations to various conditions such as temperature, pH and ionic strength changes. In this work we describe the development of a urea biosensor by immobilizing Proteus mirabilis bacteria onto an insulator-semiconductor electrode on functionalized Fe3O4 nanoparticles (NPs), using cationic, Poly (allylamine hydrochloride) then anionic, Poly (sodium 4-styrenesulfonate) polyelectrolytes, BSA (serum bovin albumin), and glutaraldehyde as a cross-linking agent. The response of P. mirabilis to urea addition is evaluated in homogeneous and heterogeneous phases. Before the immobilization step, the activity of urease produced from the P. mirabilis bacteria was attempted using the ion ammonium selective electrodes (ISEs). Adhesion of the bacteria cells on IS electrodes have been studied using contact angle measurements. After immobilization of the bacteria, on the (Si/SiO2/Si3N4) and (Si/SiO2) substrates, the relationship between the evolution of the flat band potential ∆VFB and the urea concentration is found to be linear for values ranging from 10(-2)M to 10(-5)M.


Utilization of oral anticoagulants in Korean nonvalvular atrial fibrillation patients.
Background Although the majority of clinical guidelines indicate the use of NOAC (nonvitamin K antagonist oral anticoagulant) over vitamin K antagonist in nonvalvular atrial fibrillation patients, there is no information on real-world prescription factors that lead to a specific type of oral anticoagulant selection. Objective To evaluate the prescription factors for choosing a specific oral anticoagulant for nonvalvular atrial fibrillation patients in Korea. Setting Nationwide sampled database in South Korea. Methods In this study, we defined nonvalvular atrial fibrillation patients as having one or more hospitalizations or two or more out-patient visits with a stroke risk score (CHA2DS2-VASc scores) ≥ 2 eligible for oral anticoagulant therapy from Jan 1st, 2016 to Dec 31st, 2016. Baseline characteristics were analyzed, including sex, age, comorbidities, CHA2DS2-VASc, bleeding risk score (mHAS-BLED), prescribing specialty, insurance type, medical institution type and location. Univariate and multivariate logistic regression analyses were conducted for being prescribed NOAC compared with vitamin K antagonist. Main outcome measure Adjusted odds ratio of the NOAC group and vitamin K antagonist group. Results Of 9,226 patients eligible for oral anticoagulant therapy, 4999 patients (54.2%) received oral anticoagulant therapy, and 4517 patients took NOAC or vitamin K antagonist only during the study period. Prior stroke, transient ischemic attack, thromboembolism, thyroid disease, dyslipidemia, cancer, mHAS-BLED ≥ 5, in-patient care, and specialty in internal medicine and neurology were positive predictors of NOAC use over vitamin K antagonist, whereas young age (≤64), renal dysfunction, and secondary care institution were negative predictors of NOAC use over vitamin K antagonist. Conclusions The presence of comorbidities was linked to NOAC use over vitamin K antagonist, which is different from prescription factor studies in other countries and requires further study.


Side effects of atypical antipsychotics: a brief overview.
This paper reviews the available evidence concerning the side effects of atypical antipsychotics, including weight gain, type II diabetes mellitus, hyperlipidemia, QTc interval prolongation, myocarditis, sexual side effects, extrapyramidal side effects and cataract. Some recommendations about how to prevent and manage these side effects are also provided. It is concluded that atypical antipsychotics do not represent a homogeneous class, and that differences in side effects should be taken into account by clinicians when choosing an antipsychotic for an individual patient.