Accuracy of frozen section diagnosis at surgery in pre- malignant and malignant lesions of the endometrium.
The purpose of this study was to correlate the histological diagnosis made during intraoperative frozen section examination of hysterectomies with atypical hyperplasia or carcinoma, with the definitive paraffin section histology. Frozen section pathology results of patients with a preoperative biopsy showing atypical hyperplasia or endometrial carcinoma (87 patients) were compared retrospectively with paraffin section pathology findings. Those patients with curettage specimens showing atypical hyperplasia or curettings suspicious of endometrioid carcinoma had intraoperative frozen section to determine whether an invasive lesion was present and whether they required pelvic lymphadenectomy. The purpose of frozen section assessment in those patients who had a preoperative curettage specimen showing endometrial carcinoma was to identify poor prognostic pathological factors related to histological subtype, grade, depth of myometrial invasion and cervical involvement. The correlation between frozen sections and paraffin histology in patients with endometrial carcinoma was 98.6% (69/70) for histological sub-type and 84.3% (59/70) for grade of differentiation. Depth of myometrial invasion was accurately diagnosed in 94.3% (66/70) while cervical involvement was accurately assessed in 86.7% (52/60). Of the 37 patients with atypical hyperplasia or suspicious curettings on preoperative curettage who had intraoperative frozen section, 23 patients had invasive malignancy, which was confirmed in subsequent paraffin sections. Of the remaining 14 patients with a non-malignant frozen section diagnosis, 11 were confirmed with paraffin sections while three had a small well differentiated invasive lesion, two were FIGO Stage 1a and one had microscopic invasion into the myometrium. Intraoperative frozen section is a useful procedure to identify poor prognostic pathological factors as well as to diagnose endometrial cancer in patients undergoing hysterectomy for a preoperative biopsy diagnosis of atypical hyperplasia.


The effects of ethylenediamine in the rat small intestine: a powerful relaxant of the muscularis.
The pharmacology of ethylenediamine (EDA) actions in the rat small intestine was examined using isolated gut-bath preparations of proximal segments of the duodenum, jejunum, and ileum. EDA evoked concentration-dependent tetrodotoxin-insensitive relaxations of the intestine, evidently by direct action on the muscularis. Such actions were simultaneous on the longitudinal and circular muscle layers. Investigation of EDA actions on the circular muscle showed that EDA actions were unrelated to any intrinsic GABAergic mechanisms. Moreover, EDA interacted with muscle sites distinct from ATP, histamine, bradykinin, muscarinic, and adrenergic receptors. The ability of EDA to relax the intestinal musculature was generally greater than the smooth muscle relaxant papaverine and substantially better than nicotinic stimulation of the intrinsic inhibitory neurones. It would appear that EDA may be useful as a direct acting smooth muscle relaxant for the study of the physiology-pharmacology of the rodent small intestine.


Industry-funded positive studies not associated with better design or larger size.
Previous studies have associated commercial funding with positive outcomes in orthopaedic research. Those reports, however, failed to account for potential confounding variables that can lead to a disproportion of positive outcomes, including sample size, study design, and study quality. We tested the hypothesis that nonscientific factors (funding source, orthopaedic subspecialty, and geographic region of origin) are associated with positive study outcomes, but not the result of differences in study design, study quality, or sample size. All 747 abstracts presented at the 2004 American Academy of Orthopaedic Surgeons annual meeting underwent blinded analysis using previously published criteria. Studies that received commercial funding were more likely to conclude with positive outcomes. Subspecialty and country of origin were not associated with positive outcomes. Commercially funded studies were not more likely than non-funded studies to be well-designed. When control groups were used, those in commercially funded studies were not larger than those used in nonfunded studies. Our data suggest commercial funding was associated with positive outcomes, but we found no evidence to suggest commercially funded studies were better designed or larger than non-funded studies.


Strains of Mycobacterium tuberculosis differ in susceptibility to reactive nitrogen intermediates in vitro.
The effects on the viability of Mycobacterium tuberculosis strains and one Mycobacterium bovis strain from exposure to sodium nitrite for 24 h, in both neutral and acidic media, were tested. The in vitro resistance of mycobacteria to reactive nitrogen intermediates, generated at an acidic pH, was found to have a significant (P < 0.05) positive correlation to the virulence of strains in guinea pigs.


c-CBL regulates melanoma proliferation, migration, invasion and the FAK-SRC-GRB2 nexus.
Melanoma is one of the most aggressive and lethal forms of skin cancer. Despite recent improvements in targeted therapies, many patients with advanced disease fail to achieve lasting tumor regression. Therefore, it is important to develop novel druggable targets that can be exploited to improve clinical outcome. Here, we studied the role of Casitas B-lineage lymphoma (c-CBL), an E3 ubiquitin ligase, in human melanoma. Employing quantitative real-time PCR and Western blot analysis in a panel of human melanoma cell lines (A375, G361, Hs-294T, SK-Mel-2, SK-Mel-28 and 451Lu), we found that c-CBL is strongly expressed in human melanoma cells at the mRNA and protein levels. Further, we determined c-CBL levels in clinical samples of melanomas and benign melanocytic nevi, using quantitative Nuance multispectral imaging. Compared to benign nevi, melanomas showed an overlapping range of c-CBL immunoreactivity. Small interfering RNA (siRNA)-mediated knockdown of c-CBL resulted in decreased proliferation, clonogenic survival and migration of melanoma cells. Furthermore, it also resulted in decreased cellular invasion in a 3D spheroid assay system. C-CBL and FAK are regulated by SRC, and FAK binds SRC and GRB2. C-CBL E3 ligase domain regulates receptor tyrosine kinase internalization through ubiquitination and its ring finger domain stabilizes the FAK-SRC-actin cytoskeleton thereby promoting cellular motility. C-CBL knockdown was associated with decreased protein and/or mRNA levels of SRC, FAK and GRB2. Taken together, we have provided evidence that c-CBL plays a role in melanoma cell proliferation, migration and invasion as well as inhibition of the FAK-GRB2-SRC nexus. Our findings indicate that additional studies are warranted to further dissect the role of c-CBL in melanoma and determine the therapeutic potential of its inhibition.


Warts, malnutrition, and sunshine.
Viral warts are common in poor rural settings but their relationship to malnutrition has not been studied. We sought to determine the prevalence of warts in children of two communities in Oaxaca, Mexico, and compared it with their nutritional status. Children from Santa Catarina Yahuio and Santiago Laxopa of the state of Oaxaca were examined. Localization, number, and type of verruca were noted. Date of birth, height, and weight were obtained to determine nutritional status. A total of 213 children (116 girls and 97 boys), 107 in Yahuio and 106 in Laxopa, were studied. Mean age was 10.24 years. Thirty children (14.1%) had warts and 80% (24/30) of these lived in Yahuio (p = 0.0002). Almost half were teenagers. Most lesions were on sun-exposed areas. First degree malnutrition was found in 24.5%; second degree in 23.6% and third degree in 14.2%. A higher frequency of warts than previously reported was found. Malnutrition was prevalent in both groups but did not correlate positively with verruca. Verruca were more frequent in females, adolescents, sun-exposed areas, and higher altitude. We believe that the higher altitude of Yahuio facilitates greater exposure to ultraviolet light-induced immune suppression.


Childhood tuberculosis diagnosed and managed as asthma: case report.
The worldwide incidence of tuberculosis (TB) has been increasing. Although its diagnosis is well established in adults, in children it is difficult due to its particular aspects. We report a 3 years and 8 month-old infant who experienced chronic wheezing, classified as moderate-to-severe asthma, had recurrent pneumonia, and was not responsive to management with beta adrenergic agents. Chest X-rays (CXR) showed heterogeneous condensation in medium lobe and the chest computerized-tomography scan (CCT) a heterogeneous increase in pulmonary transparency, like condensation in the same lobe. After four months of treatment with anti tuberculosis agents, a significant improvement in symptoms, normal CXR, absence of pulmonary medium lobe condensation, and persistence fibro-atelectatic band in lingula were observed.


K2SrP4O12: a deep-UV transparent cyclophosphate as a nonlinear optical crystal.
Benefiting from high transmittance of PO4 tetrahedra in the deep-ultraviolet (deep-UV) region, phosphates have been investigated as deep-UV nonlinear optical (NLO) candidates for years. So far, reported deep-UV NLO phosphates are orthophosphates and polyphosphates while cyclophosphates, important members of the phosphates family, have usually been neglected for use as deep-UV NLO crystals. Here, we first report a novel cyclotetraphosphate K2SrP4O12 (KSPO) as a deep-UV transparent NLO crystal. In its structure, the fundamental building groups are ring [P4O12]4- groups. KSPO exhibits a moderate second-harmonic generation (SHG) response that is 0.5 times that of KH2PO4 (KDP) and a short deep-ultraviolet absorption edge smaller than 200 nm.


Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection.
To compare the effectiveness of radio-frequency (RF) ablation with that of percutaneous ethanol injection in the treatment of small hepatocellular carcinoma (HCC). Eighty-six patients with 112 small (< or = 3-cm-diameter) HCCs underwent RF ablation (42 patients with 52 tumors) or percutaneous ethanol injection (44 patients with 60 tumors). Therapeutic efficacy was evaluated with dual-phase spiral computed tomography performed at least 4 months after treatment. Complete necrosis was achieved in 47 of 52 tumors with RF ablation (90%) and in 48 of 60 tumors with percutaneous ethanol injection (80%). These results were obtained with an average of 1.2 sessions per tumor with RF ablation and 4.8 sessions per tumor with percutaneous ethanol injection. One major complication (hemothorax that required drainage) and four minor complications (intraperitoneal bleeding, hemobilia, pleural effusion, cholecystitis) occurred in patients treated with RF ablation; no complications occurred in patients treated with percutaneous ethanol injection. RF ablation results in a higher rate of complete necrosis and requires fewer treatment sessions than percutaneous ethanol injection. However, the complication rate is higher with RF ablation than with percutaneous ethanol injection. RF ablation is the treatment of choice for most patients with HCC.


Stone bone syndrome--diffuse sclerosis of bone: a newly described clinical disorder.
A 52-year-old man with severe bone pain was found to have diffuse sclerosis of bone and chronic hepatitis C infection. A bone biopsy specimen showed a normal lamellar appearance but dramatically increased bone-forming surfaces. A possible mechanism for this disorder is offered.


Implementing a Universal Cervical Length Screening Program in a Large Hospital System: It Takes Some Time to Achieve Consistent Results.
The aim of the study was to describe changes in the acceptance of transvaginal (TV) cervical length (CL) assessment and in the variance of CL measurements among operators, after implementation of universal TV-CL screening at 18+0 - to 23+6 weeks/days of gestation. Retrospective cohort. This study was performed after universal TV-CL screening was implemented at the University of Texas Health Science Center in Houston, TX, USA, for all women undergoing an anatomy ultrasound (US) between 18 0/6 and 23 6/7 weeks/days of gestation. Pregnant women carrying singletons without prior history of preterm delivery who underwent anatomy US evaluation between September 2017 and March 2020 (30 months) were included. The complete study period was divided into five epochs of 6 months each. Changes in patient's acceptance for the TV scan, in CL distribution, in the prevalence of short cervix defined as ≤15, ≤20, or ≤25 mm, and in the performance of US operators across the five epochs were evaluated. Success rate was defined as the percentage of TV-CL measurements obtained in relation to the number of second-trimester anatomy scans. A total of 22,207 low-risk pregnant women evaluated by 36 trained sonographers (operators) were analyzed. Overall, the acceptance for TV-CL measurement was 82.3% (18,289/22,207), increasing from 76.7% in the first epoch to 82.8% (p < 0.0001) in the last epoch. The mean CL did not significantly change from 38.6 mm in the first epoch to 38.5 mm in the last epoch (p = 0.7); however, the standard deviation decreased from 7.9 mm in the first epoch to 7.04 mm in the last epoch (p = <0.01). The prevalence of a short cervix ≤25 mm was 2.2% (n = 399/18,289), ≤20 mm was 1.2% (224/18,289), and ≤15 mm was 0.9% (162/18,289). This prevalence varied only for CL ≤25 mm from 3.02% (88/2,907) in the first epoch to 1.77% (64/3,615) in the last epoch (p = 0.0009). There was a variation in CL measurements among operators (mean 3.3 mm). Sonographers with less than 1 year of experience had a lower success rate for completing TV-CL examinations than more experienced sonographers (80.8% vs. 85.8%; p < 0.03). In general, 77% (27/35) of operators had a success rate ≥80% for completing TV-CL scans. Characteristics of individuals who accepted versus those who declined TV-CL were not compared; CL values were not correlated with clinical outcomes. During the first 6 months after implementation of a universal CL screening program, there was greater variation in CL measurements, lower acceptance for TV US, and a higher number of women diagnosed with a CL ≤25 mm, as compared to subsequent epochs. After the first 6 months, these metrics improved and remained stable. Most operators improved their performance over time; however, there were a few with a low success rate for TV-CL and others who systematically over- or underestimate CL measurements.


Long-term right ventricular assist device support for congenitally corrected transposition of the great arteries.
With congenitally corrected transposition of the great arteries, the right ventricle (RV) supports the systemic circulation. These patients have an increased risk of developing heart failure. Implantation of a ventricular assist device may be the only therapeutic option for patients who are not transplantation candidates. The technical aspects of implanting a mechanical device into the RV have not been well described, however. We describe our experience with one such case and describe our operative strategy in obtaining optimal placement of the inflow cannula.


[Modulation of granulocyte phagocytosis].
Non-specific complications are encountered relatively often in patients with below normal granulocytic phagocytosis rates. We tested vitamin C, transfer factor, gamma-globulin, BCG, PPD, UV irradiation of the subject's blood (UVB) and hyaluronidase with the aim of stimulating granulocytic phagocytosis with rice starch in autologous serum. In our experiments, only the addition of hyaluronidase caused any increase in phagocytotic activity. The in vitro experiments with hyaluronidase yielded promising results and will be followed up since they may be relevant to practical questions.


Regulation of the KNOX-GA gene module induces heterophyllic alteration in North American lake cress.
Plants show leaf form alteration in response to changes in the surrounding environment, and this phenomenon is called heterophylly. Although heterophylly is seen across plant species, the regulatory mechanisms involved are largely unknown. Here, we investigated the mechanism underlying heterophylly in Rorippa aquatica (Brassicaceae), also known as North American lake cress. R. aquatica develops pinnately dissected leaves in submerged conditions, whereas it forms simple leaves with serrated margins in terrestrial conditions. We found that the expression levels of KNOTTED1-LIKE HOMEOBOX (KNOX1) orthologs changed in response to changes in the surrounding environment (e.g., change of ambient temperature; below or above water) and that the accumulation of gibberellin (GA), which is thought to be regulated by KNOX1 genes, also changed in the leaf primordia. We further demonstrated that exogenous GA affects the complexity of leaf form in this species. Moreover, RNA-seq revealed a relationship between light intensity and leaf form. These results suggest that regulation of GA level via KNOX1 genes is involved in regulating heterophylly in R. aquatica. The mechanism responsible for morphological diversification of leaf form among species may also govern the variation of leaf form within a species in response to environmental changes.


Snakes and ladders: localized solutions of plane Couette flow.
We demonstrate the existence of a large number of exact solutions of plane Couette flow, which share the topology of known periodic solutions but are localized in one spatial dimension. Solutions of different size are organized in a snakes-and-ladders structure strikingly similar to that observed for simpler pattern-forming partial differential equations. These new solutions are a step towards extending the dynamical systems view of transitional turbulence to spatially extended flows.


Neural responses to food stimuli among individuals with eating and weight disorders: a systematic review of event-related potentials.
A systematic review was conducted to investigate event-related potentials (ERPs) in response to food and non-food stimuli among individuals with eating and weight disorders. Limiting the search to studies that have analysed ERPs relating to motivated attention and inhibitory control, 19 research papers were extracted from a systematic search in PubMed, Ovid, and Web of Science (2000-2018). An enhanced attentional bias towards food over non-food images (as indexed by P3(00) and LPP amplitudes) was evident for all populations. Individuals with binge eating disorder showed an enhanced attentional response to food cues compared to healthy controls. Inhibitory control-related ERP components (N2(00) and P3a) increased during food-specific no-go trials, but did not differentiate overweight from 'healthy' weight groups. The N2 amplitude to food pictures were positively correlated with caloric intake and food craving among individuals with obesity and binge eating disorder, respectively, while P3(00) was sensitive to hunger levels among overweight and obese females. The heterogeneity of stimuli/paradigms adopted, component timescales extracted, ERPs analysed, and data presented has challenged this review's ability to produce a robust synthesis of results. Some recommendations for future research are discussed.


Do Javan gibbons (Hylobates moloch) use fruiting synchrony as a foraging strategy?
Tropical rainforests are characterized by a high diversity of plant species. Each plant species presents with differential phenological patterns in fruit production. In some species, all individual trees produce fruit simultaneously within clustered periods; whereas in others, each individual tree fruits at irregular time intervals. By observing this pattern, some primate species use the presence of fruits in one tree as a cue to find fruit in other trees of the same synchronously fruiting tree species. Here, we investigated whether the highly frugivorous Javan gibbons (Hylobates moloch) in Gunung Halimun-Salak National Park in Indonesia have knowledge of synchronous characteristics of fruiting trees and whether they can further distinguish fruit species with different synchrony levels, that is, tree species with highly synchronous fruiting patterns versus tree species with less synchronous fruiting patterns. Across 12 months we collected biweekly phenological data on 250 trees from 10 fruit species and observed Javan gibbons' visits to those species. We found that a fruit discovery in the beginning of fruiting seasons triggered gibbons to visit trees of the same fruit species. However, gibbons' visit rates did not differ between highly synchronous and asynchronous species. Our results suggest that Javan gibbons have knowledge of synchronous characteristics of fruiting trees in general, but they do not differentiate highly synchronous versus asynchronous fruit species. We speculate that Javan gibbons, who live in relatively small ranges with very low tree density of preferred fruit species, are likely able to track and remember fruiting states of individual trees without needing to distinguish fruit species with different synchrony levels. Moreover, gibbons may make little benefit of distinguishing highly synchronous versus asynchronous fruit species, probably due to gibbons' heavy use of asynchronous figs. Our study provides an insight into how gibbon's foraging strategies may have been shaped in response to their ecological environment.


Capillary electrophoresis with electrochemiluminescence detection for simultaneous determination of proline and fleroxacin in human urine.
The content of free proline (Pro) in body fluids is a biological parameter for patients with renal insufficiency and chronic uraemia. Fleroxacin (FLX) must be used cautiously because of adverse reactions. Its dosage must be adjusted according to the degree of renal insufficiency. In a clinical setting the simultaneous determination of Pro and FLX in body fluids is necessary for the rational utilization of FLX. A capillary electrophoresis (CE) method based on electrochemiluminescence (ECL) detection with Ru(bpy)(3) (2+) was developed for the simultaneous determination of Pro and FLX in human urine. Parameters related to separation and detection were investigated and optimized. The most favourable resolution and high sensitivity were obtained using a 15 mM phosphate buffer at pH 9.6 with the detection potential at 1.15 V. Under optimized conditions, the standard curves were linear in the range of 0.1-80 microg/mL for Pro and 0.1-100 microg/mL for FLX. Detection limits(3sigma) of 0.3 ng/mL for FLX and 0.02 microg/mL for Pro were obtained. Relative standard derivations (RSDs) of the ECL intensity and the migration time were 3.2% and 0.9% for 4 microg/mL Pro and 3.7% and 1.2% for 4 microg/mL FLX, respectively. The recoveries were in the range of 94.8-99.6% for Pro with RSDs of 2.8%-3.6% and 94.7-97.8% for FLX with RSDs of 2.9%-3.7%. The proposed method was successfully applied to determine the amounts of Pro and FLX in human urine.


Orthopaedic Snafus: When Adverse Events Happen in Orthopaedics.
The potential for adverse events exists when treating and managing orthopaedic patients in the intraoperative or postoperative environments, especially when it comes to falls, surgical site infections, venous thromboembolism, and injuries to nerves and blood vessels. Orthopaedic nurses play a vital role in the promotion and use of evidence-based interventions to decrease the incidence of these adverse events, improve quality of care, and minimize the financial burden related to these adverse events.


Superiority illusion arises from resting-state brain networks modulated by dopamine.
The majority of individuals evaluate themselves as superior to average. This is a cognitive bias known as the "superiority illusion." This illusion helps us to have hope for the future and is deep-rooted in the process of human evolution. In this study, we examined the default states of neural and molecular systems that generate this illusion, using resting-state functional MRI and PET. Resting-state functional connectivity between the frontal cortex and striatum regulated by inhibitory dopaminergic neurotransmission determines individual levels of the superiority illusion. Our findings help elucidate how this key aspect of the human mind is biologically determined, and identify potential molecular and neural targets for treatment for depressive realism.


Interest in Mindfulness Training for Chronic Low-Back Pain: Results from a Vignette-driven, Web-based Survey of Patients.
Objectives: Mindfulness-based stress reduction (MBSR) has been found effective for improving chronic low-back pain (cLBP). However, little data exist regarding how attractive this technique is to Americans as a therapy for cLBP. Design: Survey of randomly selected persons with cLBP. Settings/Location: Respondents were recruited from Kaiser Permanente Washington and one-time surveys were completed online. Patients: Adults 18-80 years of age with cLBP. Surveys: The study was conducted between December 2019 and August 2020. Outcome measures: The survey described an evidence-based classic MBSR course and then asked respondents about their sociodemographic characteristics, their current back pain, previous back pain treatments, behavioral risk factors for back pain, and four outcomes indicative of intention to engage in MBSR. Results: Four-hundred fifty-seven respondents completed the survey. Respondents were primarily women, white, educated, and with back pain for more than 5 years. About half had previously used a mind-body therapy for their pain. Overall, they reported moderate to high intention to try mindfulness classes and practice at home (median of 5 with 50% of the observations between 4 and 6, and 5.7, 50% of the observations between 4.3 and 6.3, respectively, on a 7-point scale). They reported a willingness to spend a median of 3 h/week learning mindfulness and 3.5 h/week practicing mindfulness techniques (for both outcomes, 50% of the respondents reported between 2 and 5 h). Few patient characteristics predicted intention to engage in MBSR, with no variable predicting all outcomes. The magnitude of the effect associated with significant predictors was small. Conclusion: Classic MBSR appealed to many survey respondents, in that they reported high interest in learning MBSR and intention to practice at home. The amount of time they reported being willing to spend learning MBSR and practicing at home is consistent with the time commitment in the original course.


Midbrain circuits for defensive behaviour.
Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla. In addition, we provide evidence for anatomical and functional interaction of this freezing pathway with long-range and local circuits mediating flight. Our data define the neuronal circuitry underlying the execution of freezing, an evolutionarily conserved defensive behaviour, which is expressed by many species including fish, rodents and primates. In humans, dysregulation of this 'survival circuit' has been implicated in anxiety-related disorders.


[Various features of the hemodynamics of native inhabitants of different mountainous zones of the Mongolian People's Republic].
The native inhabitants of Mongolia living at relatively moderate altitudes (2200-2300 m) showed a statistically decreased heart rate, elevated venous pressure, cardiac output and stroke volume as well as a reduced rate of the blood flow which should be considered as compensatory responses to high altitude and cold hypoxia. In inhabitants of colder zones the systolic pressure was 132 +/- 1.2 mm Hg, the diastolic pressure was 83.8 +/- 0.6 mm Hg as against 122.8 +/- 1.0 and 77.6 +/- 0.6 mm Hg, respectively, in inhabitants of warmer zones (p less than 0.01). The incidence of blood hypertension in 40-69-year-olds in cold zones equaled 19 +/- 2.5% as compared to 8.3 +/- 2.1% (p less than 0.01) in warmer high altitude zones. No correlation was found between the subjects' blood pressure and the altitude of their place of living which suggests that high altitude hypoxia has no decisive effect on the blood pressure and that the significantly higher prevalence of hypertension in cold zones can be explained by the impact of a complex of adverse climate and geographic factors, with low temperatures being especially important.


Autocrine/paracrine TGF-β1 inhibits Langerhans cell migration.
Langerhans cells (LCs) are skin-resident dendritic cells (DC) located in the epidermis that migrate to skin-draining lymph nodes during the steady state and in response to inflammatory stimuli. TGF-β1 is a critical immune regulator that is highly expressed by LCs. The ability to test the functional importance of LC-derived TGF-β1 is complicated by the requirement of TGF-β1 for LC development and by the absence of LCs in mice with an LC-specific ablation of TGF-β1 or its receptor. To overcome these problems, we have engineered transgenic huLangerin-CreER(T2) mice that allow for inducible LC-specific excision. Highly efficient and LC-specific expression was confirmed in mice bred onto a YFP Cre reporter strain. We next generated huLangerin-CreER(T2) × TGF-βRII(fl) and huLangerin-CreER(T2) × TGF-β1(fl) mice. Excision of the TGFβRII or TGFβ1 genes induced mass migration of LCs to the regional lymph node. Expression of costimulatory markers and inflammatory cytokines was unaffected, consistent with homeostatic migration. In addition, levels of p-SMAD2/3 were decreased in LCs from wild-type mice before inflammation-induced migration. We conclude that TGF-β1 acts directly on LCs in an autocrine/paracrine manner to inhibit steady-state and inflammation-induced migration. This is a readily targetable pathway with potential therapeutic implications for skin disease.


Future costs of stroke in the Netherlands: the impact of stroke services.
In the next decades, the number of stroke patients is expected to increase. Furthermore, organizational changes, such as stroke services, are expected to be implemented on a large scale. The purpose of this study is to estimate the future healthcare costs by taking into account the expected increase of stroke patients and a nationwide implementation of stroke services. By means of a dynamic multistate life table, the total number of stroke patients can be projected. The model calculates the annual number of patients by age and gender. The total healthcare costs are calculated by multiplying the average healthcare costs specified by age, gender, and healthcare sector with the total number of stroke patients specified by age and gender. In the year 2000, the healthcare costs for stroke amounted to euro 1.62 billion. This amount is approximately 4.4 percent of the total national healthcare budget. Projections of the total costs of stroke based on current practice result in an increase of 28 percent (euro 2.08 billion) in the year 2020. A nationwide implementation of stroke services in 2020 would result in a substantial reduction of the costs of stroke (euro 1.81 billion: 13 percent cost reduction) compared with the regular care scenario. A nationwide implementation of stroke services is a strong policy tool for cost containment of health care in an aging population like that in the Netherlands. Policy makers should optimize the organization of stroke care.


External electric field induced hydrogen storage/release on calcium-decorated single-layer and bilayer silicene.
Hydrogen storage and release are two essential parameters that define the efficiency of a hydrogen storage medium. Herein, we investigate the effects of the external electric field F on the adsorption-desorption of H2 on a Ca-decorated silicene system (Ca-silicene) based on density functional theory calculations. Our study demonstrates that nine H2 molecules per Ca atom can be adsorbed and 6.4 wt% H2 can be adsorbed on Ca-silicene with an average binding energy of 0.19 eV per H2, while the appropriate F can be used to effectively enhance the hydrogen storage-release on the Ca-silicene system. The high synergetic effect may be attributed to the observation that F induces an enhancement of the charge transfer between H2 molecules and the Ca-silicene system. Thus, the Ca-silicene system together with the synergy of F can efficiently facilitate H2 adsorption-desorption, completing the whole hydrogen storage-release cycle.


Ventricular tachycardia in cardiac sarcoidosis: characterization of ventricular substrate and outcomes of catheter ablation.
Cardiac sarcoid-related ventricular tachycardia (VT) is a rare disorder; the underlying substrate and response to ablation are poorly understood. We sought to examine the ventricular substrate and outcomes of catheter ablation in this population. Of 435 patients with nonischemic cardiomyopathy referred for VT ablation, 21 patients (5%) had cardiac sarcoidosis. Multiple inducible VTs were observed with mechanism consistent with scar-mediated re-entry in all VTs. Voltage maps showed widespread and confluent right ventricular scarring. Left ventricular scarring was patchy with a predilection for the basal septum, anterior wall, and perivalvular regions. Epicardial right ventricular scar overlay and exceeded the region of corresponding endocardial scar. After ≥1 procedures, ablation abolished ≥1 inducible VT in 90% and eliminated VT storm in 78% of patients; however, multiple residual VTs remained inducible. Failure to abolish all inducible VTs was because of septal intramural circuits or extensive right ventricular scarring. Multiple procedure VT-free survival was 37% at 1 year, but VT control was achievable in the majority of patients with fewer antiarrhythmic drugs compared with preablation (2.1±0.8 versus 1.1±0.8; P<0.001). Patients with cardiac sarcoidosis and VT exhibit ventricular substrate characterized by confluent right ventricular scarring and patchy left ventricular scarring capable of sustaining a large number of re-entrant circuits. Catheter ablation is effective in terminating VT storm and eliminating ≥1 inducible VT in the majority of patients, but recurrences are common. Ablation in conjunction with antiarrhythmic drugs can help palliate VT in this high-risk population.


Effects and mechanism of action of terbutaline on diaphragmatic contractility and fatigue.
We studied the effects of intravenously administered terbutaline on diaphragmatic force and fatigue during electrical stimulation of the diaphragm in 17 anesthetized dogs. The diaphragm was stimulated indirectly through the phrenic nerves with electrodes placed around the fifth roots and directly with electrodes surgically implanted in the abdominal side of each hemidiaphragm. Transdiaphragmatic pressure (Pdi) during direct or indirect supramaximal 2-s stimulation applied over a frequency range of 10-100 Hz was measured with balloon catheters during tracheal occlusion at functional residual capacity. In seven dogs the administration of terbutaline (0.5 mg) had no effect on Pdi at any stimulation frequency applied directly or indirectly. The effect of terbutaline (0.5 mg) on diaphragmatic fatigue was then tested in 10 other dogs. Diaphragmatic fatigue was produced by continuous 20-Hz electrical supramaxial stimulation of the phrenic nerves during 30 min. At the end of the fatigue procedure Pdi decreased by 50 +/- 5 and 30 +/- 8% of control values at 10 and 100 Hz, respectively, for either direct or indirect stimulation. The decrease in Pdi for low frequencies of stimulation (10 and 20 Hz) lasted 100 +/- 18 min, whereas it lasted only 40 +/- 10 min for the high frequencies (50 and 100 Hz). When terbutaline (0.5 mg) was administered after the fatiguing procedure, Pdi increased within 15 min by 20 +/- 4% at 10 Hz and by 12 +/- 3% at 100 Hz for either direct or indirect stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Persistent bacterial infections and persister cells.
Many bacteria can infect and persist inside their hosts for long periods of time. This can be due to immunosuppression of the host, immune evasion by the pathogen and/or ineffective killing by antibiotics. Bacteria can survive antibiotic treatment if they are resistant or tolerant to a drug. Persisters are a subpopulation of transiently antibiotic-tolerant bacterial cells that are often slow-growing or growth-arrested, and are able to resume growth after a lethal stress. The formation of persister cells establishes phenotypic heterogeneity within a bacterial population and has been hypothesized to be important for increasing the chances of successfully adapting to environmental change. The presence of persister cells can result in the recalcitrance and relapse of persistent bacterial infections, and it has been linked to an increase in the risk of the emergence of antibiotic resistance during treatment. If the mechanisms of the formation and regrowth of these antibiotic-tolerant cells were better understood, it could lead to the development of new approaches for the eradication of persistent bacterial infections. In this Review, we discuss recent developments in our understanding of bacterial persisters and their potential implications for the treatment of persistent infections.


Bioinspired Diversification Approach Toward the Total Synthesis of Lycodine-Type Alkaloids.
Nitrogen heterocycles (azacycles) are common structural motifs in numerous pharmaceuticals, agrochemicals, and natural products. Many powerful methods have been developed and continue to be advanced for the selective installation and modification of nitrogen heterocycles through C-H functionalization and C-C cleavage approaches, revealing new strategies for the synthesis of targets containing these structural entities. Here, we report the first total syntheses of the lycodine-type Lycopodium alkaloids casuarinine H, lycoplatyrine B, lycoplatyrine A, and lycopladine F as well as the total synthesis of 8,15-dihydrohuperzine A through bioinspired late-stage diversification of a readily accessible common precursor, N-desmethyl-β-obscurine. Key steps in the syntheses include oxidative C-C bond cleavage of a piperidine ring in the core structure of the obscurine intermediate and site-selective C-H borylation of a pyridine nucleus to enable cross-coupling reactions.


A one-year review of craniofacial injuries in amateur soccer players.
The purpose of this study was to investigate the rate of craniofacial injuries in amateur soccer and help us better understand the nature of these injuries. Retrospective study was carried out using records from the patients with craniofacial injuries associated with soccer activities. All data were collected on the basis of sex, age, type and anatomic site of the injury. In the one-year period of this study, 11/53 cases with craniofacial injuries associated with soccer activities have been treated in our clinic. The highest incidence was in the 18 to 24 year age group (mean age 20.7) with male propensity. The majority of the patients suffered from dento-alveolar fractures (36%), followed by temporomandibular joint disorders (27%), mandibular fractures (27%), and nasal fractures (9%). The most common cause of the fractures was impact against another player (63.6%), followed by impact against equipment (18.2%) and impact against the ground (18.2%). These results show that there is a high risk of potential oral and craniofacial injury during soccer activities.


Teleophthalmology Prevents Unnecessary Evacuation from Warzone.
The purpose of this case report is to highlight the benefits of using teleconsultation to diagnose ophthalmologic conditions within the restraints of a combat environment. A previously healthy 49-year-old service member deployed in the Middle East presented with diplopia over the course of 2 weeks. Initial diagnosis by his primary care physician upon partial ophthalmologic exam was a pupil-sparing CN III palsy without ptosis. Initial teleconsultation response from Naval Medical Center Portsmouth was within 6 hours. After an ophthalmologic sensorimotor examination was videotaped and sent to the referred ophthalmologist, teleconsultation was completed and discussed with the patient. The updated diagnosis was CN IV palsy with slight right hypertropia worse on left gaze-most likely congenital in origin. Upon further follow-up stateside, his final diagnosis was diplopia related to thyroid disease. Overall, his diagnosis remained a nonurgent condition that allowed the service member to remain at his duty station and prevent an unnecessary evacuation. Ultimately, teleconsultation provided many benefits for the service member and the U.S. military.


Microbiota-induced peritrophic matrix regulates midgut homeostasis and prevents systemic infection of malaria vector mosquitoes.
Manipulation of the mosquito gut microbiota can lay the foundations for novel methods for disease transmission control. Mosquito blood feeding triggers a significant, transient increase of the gut microbiota, but little is known about the mechanisms by which the mosquito controls this bacterial growth whilst limiting inflammation of the gut epithelium. Here, we investigate the gut epithelial response to the changing microbiota load upon blood feeding in the malaria vector Anopheles coluzzii. We show that the synthesis and integrity of the peritrophic matrix, which physically separates the gut epithelium from its luminal contents, is microbiota dependent. We reveal that the peritrophic matrix limits the growth and persistence of Enterobacteriaceae within the gut, whilst preventing seeding of a systemic infection. Our results demonstrate that the peritrophic matrix is a key regulator of mosquito gut homeostasis and establish functional analogies between this and the mucus layers of the mammalian gastrointestinal tract.


[Hypersensitivity pneumonitis-like disease caused by exposure to Mycobacterium avium complex in bathtub water at home: a case report].
We report here a case of hypersensitivity pneumonitis-like disease in an adult, likely due to exposure to Mycobacterium avium complex (MAC) in his bathtub water at home. A 63-year-old man was referred to our hospital with exertional dyspnea. Chest computed tomography showed bilateral, diffuse, centrilobular ground-glass nodules. Bronchoalveolar lavage showed marked lymphocytosis. Transbronchial biopsy showed epithelioid cell granulomas and lymphocyte alveolitis. Cultures of the patient's sputum and bathtub water yielded MAC. Variable-number tandem repeat analysis of the MAC strains in the sputum and bathtub water samples showed that the strains were genetically identical. The clinical condition of the patient improved at home under chemotherapy by avoiding the use of the bathtub.


[Thoracocervical giant perimedullary arteriovenous fistula treated with transarterial embolization: a case report].
A 43-year-old woman with progressive gait disturbance and dysesthesia of the limbs and trunk visited our hospital. Upon examination, a thoracocervical giant perimedullary arteriovenous fistula(GPMAVF)was detected. The GPMAVF was fed by both of the highest intercostal arteries and the thyrocervical trunk. The dilated drainage vein widely compressed the spinal cord from the upper thoracic to the cervical regions. Transarterial embolization with n-butyl 2-cyanoacrylate was performed, and the fistula was completely obliterated. The dilated drainage vein was thrombosed, and it decreased in size after treatment. The patient's symptoms and magnetic resonance imaging results significantly improved. We suggest that endovascular treatment is effective for GPMAVFs, given sufficient analysis of the anatomical architecture.


Study of Frontal and Temporal Hairline Patterns in Japanese Subjects.
The shape of the hairline is very important in a person's identity and in determining the impression they make. Reports on the morphology of a normal hairline are still scarce. Differences in the shape of male and female hairlines in Japanese subjects are discussed in this study. A questionnaire about hairline type, the presence or absence of a widow's peak, and measurement of the width and height of the forehead was given to 456 healthy subjects, and their responses were recorded. Percentages of frontal hairline types were found to be linear (women 36.1%, men 45.9%), triangular (7.2%, 0.82%), round (38.5%, 10.7%), and M- shaped (18.2%, 42.6%). Temporal hairline types: inverted triangle (20.3%, 65.6%), inverted round (27.8%, 17.2%), straight (24.8%, 10.6%), and convex (27.2%, 6.6%). The incidence of a widow's peak was 29.6% in women and 32.8% in men. The mean length of the mid-frontal line was 6.2 cm in women and 6.65 cm in men. Regarding the hairline morphology of the frontal view, two types (linear and M-shaped) accounted for 88.5% of men. In women, linear accounted for 36.1%, being relatively high, but lower than the frequency in men. Round accounted for 38.5%, being the highest. Regarding the temporal hairline, a hairless region (inverted triangle and inverted round) was noted in 82.8% of men. In women, a hairless region was present in 48.1% and was absent (straight and convex) in 51.9%. A temporal hairline with a hairless region was noted in the majority of men, whereas it was absent in slightly more cases in women.


Cortical spheroid on perfusable microvascular network in a microfluidic device.
Human induced pluripotent stem cell (hiPSC)-derived brain spheroids can recapitulate the complex cytoarchitecture of the brain, as well as the genetic/epigenetic footprint of human brain development. However, hiPSC-derived 3D models such as spheroid and organoids does not have a perfusable microvascular network, which plays a vital role in maintaining homeostasis in vivo. With the critical balance of positive and negative angiogenic modulators, 3D microvascular network can be achieved by angiogenesis. This paper reports on a microfluidic-based three-dimensional, cortical spheroid grafted on the vascular-network. Vascular network was formed by inducing angiogenic sprouting using concentration gradient-driven angiogenic factors in the microfluidic device. We investigate critical factors for angiogenic vascular network formation with spheroid placement, including 1) a PKCα activator, phorbol-12-myristate-13-acetate (PMA); 2) orientation of endothelial cells under perfusion and permeability of vascular network; 3) effect of extracellular matrix (ECM) types and their densities on angiogenesis; and 4) integration with cortical spheroid on vascular network. This paper demonstrates proof of concept for the potential utility of a membrane-free in vitro cortical spheroid tissue construct with perfusable microvascular network that can be scaled up to a high throughput platform. It can provide a cost-effective alternative platform to animal testing by modeling brain diseases and disorders, and screening drugs.


Polyphenols and antioxidant capacity of seed coat and cotyledon from Brazilian and Peruvian bean cultivars (Phaseolus vulgaris L.).
Seed coats and cotyledons from 25 Brazilian and 3 Peruvian bean cultivars were investigated in relation to their phenolic profiles and antioxidant capacity. Condensed tannins, anthocyanins, and flavonols such as kaempferol and quercetin glycosides were mostly found in seed coats. Cotyledons were rich in phenolic acids, such as ferulic, sinapic, chlorogenic, and other hydroxycinnamic acids. In general, the seed coat color pattern and the type of cultivar showed an important influence on the variability of phenolic profiles and levels, respectively. Total phenolics and antioxidant capacity assessed by the DPPH method were higher in seed coats than in cotyledons. The antioxidant capacity had a significant correlation with condensed tannins for all samples and with total anthocyanins in black and red seed coats, whereas in cotyledons, it was more related to the total phenolic content.


Hiatal hernia mimicking ST elevation myocardial infarction.
A 72-year-old man with a history of hypertension, hiatal hernia, prostate cancer and lung cancer was admitted with complaints of abdominal pain, sweating and rigors. An electrocardiogram showed ST elevation in multiple leads. Noninvasive and invasive cardiovascular work-up was performed that was negative for occlusive coronary artery disease. Further studies demonstrated a large hiatal hernia; this was found to be the culprit causing his symptoms. Hiatal hernia is a very rare cause of ST segment elevation and should be considered in the differential diagnosis of disorders that can cause ST elevation.


Halogen-halogen interactions in halomethanes.
We report the study of the electronic structure of CHFI(2), CHBrI(2), CHBr(2)I, CHClI(2), and CHCl(2)I using VUV photoelectron spectroscopy (UPS). The lone pair orbital interactions are discussed on the basis of experimental results and comparisons with other halomethanes.


UCP-mediated free fatty acid uncoupling of isolated cortical mitochondria from fasted animals: correlations to dietary modulations.
Uncoupling proteins (UCP) translocate protons from the mitochondrial intermembrane space to the matrix, thereby "uncoupling" electron transport from the production of ATP. It has been shown that these proteins are highly expressed in animals maintained on the ketogenic diet (KD). Although the exact mechanism remains unclear, it is known that these proteins are activated within a protective antireactive oxygen species (ROS) mechanism by free fatty acids (FFA). In our current studies, mitochondrial samples were probed for the presence of UCP2, which is the most ubiquitously expressed UCP isoform. We found that both traumatic brain injury and fasting upregulated the expression of UCP2, with a synergistic upregulation in fasted injured animals. We then used mitochondria from fasted naive animals to screen a number of FFA for their activation of uncoupling as well as their ability to reduce ROS. We found that arachidonic acid (AA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), palmitoleic acid, myristic acid, and butyric acid increased mitochondrial uncoupling when added after oligomycin. These FFA, along with oleic acid, also reduced ROS in mitochondria incubated with oligomycin. In order to correlate our data to KD and fasting, both of which have been shown to be neuroprotective after neurologic insult, we determined the serum levels of FFA in KD and fasted animals using gas chromatography/mass spectroscopy. We also determined brain and cerebrospinal fluid (CSF) FFA levels from fasted animals.


[Paludism: emergent diagnosis. Descriptive study of 25 cases].
During the last years, the number of patients with paludism in occidental countries has raised, specially due to the increase of immigration from endemic areas and to the augmentation of international journeys to those area. A descriptive and retrospective study of the cases of paludism diagnosed at the Hospital Universitario La Princesa, was performed between January 1995 and December 2002. Twenty-five patients were diagnosed of paludism. More than half of patients (15) were immigrants coming from endemic areas and the rest were Spanish patients who had traveled to endemic places, most of them to Africa. A transfusional case was detected. Twenty-two patients didn't take prophylaxis therapy. The most usual subtype of Plasmodium was P. falciparum. Symptoms were not specific and fever was a constant feature. The period of time between the arrival in spain and the moment of diagnosis range from one to four weeks (21 patients). It is important to search for paludism infection in patients with maintained fever who have arrived from tropic regions. Prophylaxis therapy does not exclude this possibility. Response to treatment is usually satisfactory.


The relationship between self-cohesion and smartphone addiction: the mediating role of rejection sensitivity.
The increasing use of smartphones with attractive applications has yielded concerns over problematic overuse, also called smartphone addiction, thus creating a need to investigate the antecedents and pathways of this addiction. The aim of this study was to investigate the relationships between the self-cohesion dimensions of presence and consistency and smartphone addiction, and the potentially mediating role of rejection sensitivity. A total sample of 910 respondents (58% females, mean age = 34.9, SD = 13.6) participated in the study. They completed a questionnaire including demographic characteristics and queries about frequency and duration of smartphone use, as well as the Self-Cohesion Scale, the Short Version of Smartphone Addiction Scale, and the Rejection Sensitivity RS-Adult Questionnaire. Structural equation modeling was used to examine the relationships in question. The findings indicated that smartphone addiction was positively correlated with rejection sensitivity and negatively correlated with the self-cohesion dimensions of presence and consistency. Further, both presence and consistency were negatively associated with smartphone addiction and rejection sensitivity negatively mediated these relationships. Self-cohesion and rejection sensitivity appear to be important predictors of smartphone addiction. Efforts to counteract smartphone addiction should, therefore, endeavor to increase smartphone users' self-cohesion and reduce their rejection sensitivity.


COVID-19 in-patient hospital mortality by ethnicity.
There is debate about the extent to which COVID-19 affects ethnic groups differently. We explored if there was variation in hospital mortality in patients with COVID. Mortality rates in 1,276 inpatients in Bradford with test results for COVID-19 were analysed by ethnic group. The age-adjusted risk of dying from COVID-19 was slightly lower in South Asian compared to White British patients. (RR =0.87, 95% CI: 0.41 to 1.84).


LncRNA MALAT1/microRNA-30b axis regulates macrophage polarization and function.
Macrophages (Mφ) are long-lived myeloid cells that can polarize towards the proinflammatory M1 or proresolving M2 phenotype to control diverse biological processes such as inflammation, tissue damage, and regeneration. Noncoding RNA are a class of nonprotein-coding transcriptome with numerous interdependent biological roles; however, their functional interaction in the regulation of Mφ polarization and immune responses remain unclear. Here, we show antagonistic relationship between lncRNA (MALAT1) and microRNA (miR-30b) in shaping macrophage polarization and immune functions. MALAT1 expression displays a time-dependent induction during Mφ differentiation and, upon challenge with TLR4 agonist (E. coli LPS). MALAT1 knockdown promoted the expression of M2Mφ markers without affecting M1Mφ markers, suggesting that MALAT1 favors the M1 phenotype by suppressing M2 differentiation. Compared to the control, MALAT1 knockdown resulted in reduced antigen uptake and processing, bacterial phagocytosis, and bactericidal activity, strongly supporting its critical role in regulating innate immune functions in Mφ. Consistent with this, MALAT1 knockdown showed impaired cytokine secretion upon challenge with LPS. Importantly, MALAT1 exhibit an antagonistic expression pattern with all five members of the miR-30 family during M2 Mφ differentiation. Dual-luciferase assays validated a novel sequence on MALAT1 that interacts with miR-30b, a microRNA that promotes the M2 phenotype. Phagocytosis and antigen processing assays unequivocally demonstrated that MALAT1 and miR-30b are functionally antagonistic. Concurrent MALAT1 knockdown and miR-30b overexpression exhibited the most significant attenuation in both assays. In human subjects with periodontal disease and murine model of ligature-induced periodontitis, we observed higher levels of MALAT1, M1Mφ markers and downregulation of miR-30b expression in gingival tissues suggesting a pro-inflammatory function of MALAT1 in vivo. Overall, we unraveled the role of MALAT1 in Mφ polarization and delineated the underlying mechanism of its regulation by involving MALAT-1-driven miR-30b sequestration.


The Complementary and Alternative Medicine for Polycystic Ovary Syndrome: A Review of Clinical Application and Mechanism.
As a reproductive endocrine disease, polycystic ovary syndrome (PCOS) has influenced billions of women during childbearing age worldwide. Owing to its complex etiology and ambiguous pathogenesis, there is still not a specific method to cure it. Clinical treatments, such as hormone therapy and surgical treatment, have side effects. Therefore, it is essential and urgent to seek alternative treatment to solve these problems. The satisfactory efficacy of complementary and alternative medicine (CAM), such as traditional Chinese medicine (TCM), immunotherapy, medicinal foods, vitamin therapy, diet therapy, psychotherapy, spa, and oxygen therapy, in treating PCOS, has aroused an increasing number of medical workers' concern and gradually become the mainstream. This paper reviews the application of CAM in the treatment of PCOS, especially from the perspective of TCM. Meanwhile, the limitations of the literature about CAM in the treatment of PCOS are mentioned and analyzed as well.


High-resolution, on-chip RF photonic signal processor using Brillouin gain shaping and RF interference.
Integrated microwave photonics has strongly emerged as a next-generation technology to address limitations of conventional RF electronics for wireless communications. High-resolution RF signal processing still remains a challenge due to limitations in technology that offer sub-GHz spectral resolution, in particular at high carrier frequencies. In this paper, we present an on-chip high-resolution RF signal processor, capable of providing high-suppression spectral filtering, large phase shifts and ns-scale time delays. This was achieved through tailoring of the Brillouin gain profiles using Stokes and anti-Stokes resonances combined with RF interferometry on a low-loss photonic chip with strong opto-acoustic interactions. Using an optical power of <40 mW, reconfigurable filters with a bandwidth of ~20 MHz and an extinction ratio in excess of 30 dB are synthesized. Through the concept of vector addition of RF signals we demonstrate, almost an order of magnitude amplification in the phase and delay compared to devices purely based upon the slow-light effect of Brillouin scattering. This concept allows for versatile and power-efficient manipulation of the amplitude and phase of RF signals on a photonic chip for applications in wireless communications including software defined radios and beam forming.


Camptocormia induced by atypical antipsychotics and resolved by electroconvulsive therapy.
We present a depressive patient who developed mild parkinsonian signs and camptocormia after the introduction of olanzapine. She had been treated before with other antipsychotic drugs. When camptocormia was diagnosed, olanzapine was withdrawn and levodopa was introduced. Depressive symptoms got worse and electroconvulsive therapy was tried. When the treatment was completed, her depression substantially improved and her posture became completely upright.


Medication comprehension and safety in older adults.
Older adults constitute just 13% of the U.S. population, but consume 35% of all prescription drugs. They are at a particularly high risk of serious adverse events due to errors in medication-taking, but little is known about the instructions community-dwelling elders receive about their medications, or how they organize their medications at home. This Issue Brief summarizes research that describes home-based patterns of medication use in elderly patients, and for one high-risk medication, analyzes the relationship between recall of instructions and subsequent drug-related hospitalizations. These findings may help clinicians better predict and monitor their patients' adherence to prescription drug regimens.


Minoxidil in the treatment of refractory hypertension due to a spectrum of causes.
Minoxidil in combination with propranolol and diuretics was used in the treatment of 41 patients with severe refractory hypertension due to a spectrum of causes. These etiologies included essential hypertension, advanced renal failure, renovascular hypertension, and kidney transplant rejection. All patients had evidence of renal and cardiac damage prior to therapy and had failed to respond to all standard medications. The study included patients treated for periods of 3--42 months. Forty of the 41 patients responded most impressively to this therapy. Minoxidil was given in a dose of 7.5--40 mg daily. No tolerance to minoxidil was observed. Side effects were minimal. Three myocardial infarcts were observed. Two of these patients had had previous infarcts. One patient suffered a fatal cerebrovascular accident after he had deliberately stopped all medications. Nine patients showed sodium retention, which was easily controlled in 8 cases. Mild hirsutism was occasionally seen. Mean serum creatinine levels showed a slight decrease in the essential hypertension group after treatment. Best long-term results were seen in the essential hypertension and renovascular groups, although several cases with advanced renal disease and with kidney transplant rejection hypertension showed very impressive and encouraging outcomes.


Evidence for power-law dominated noise in vacuum deposited CaF2.
We have studied the surface roughness of CaF2 vacuum deposited on glass using atomic force microscopy for film coverages spanning an order of magnitude. We find the roughness exponent alpha=0.88+/-0.03, the growth exponent beta=0.75+/-0.03, and the dynamic exponent z=alpha/beta=1.17+/-0.06. Multifractality is also present, along with power-law behavior in the nearest neighbor height difference probability distribution. The results indicate noise dominated by a power-law distribution with exponent micro+1 approximately 4.6.


Trends in caries experience of 12-year-old children in east European countries.
This paper reviews published data on the caries experience of 12-year-old children in east European countries, including the 14 states of the former Soviet Union. With the exception of the Czech Republic (2.7) all DMFT indices in the east European countries were within the range of 3.1 (Bulgaria) to 5.1 (Poland). For the states of the former Soviet Union the DMFT indices were higher in the northern regions (range 3.3 in Belorussia to 7.7 in Latvia) than in the southern regions (1.2 in Tadzikistan to 3.1 in Kirgizia). Other than in southern states of the former Soviet Union, 'low' or 'moderate' caries experience (by WHO criteria) were found only in countries with developed oral health care systems. In most of the other countries implementation of oral health promotion and prevention at the community level is needed.


Health information sources accessed by college females: differences between body-image distorted and non-body-image distorted.
This study examined and compared sources of health-related information accessed by female college students with and without body image distortions, and the believability of those sources. Survey data from the American College Health Association, National College Health Assessment were studied retrospectively (N = 27,648). Body image distorted (BID) and non-BID students' most frequent health information sources were parents (76.1% BID; 77.1% non-BID) and internet (70.3% BID; 69.5% non-BID). Believability was greatest for health educators (90.6% BID; 91.1% non-BID) and lowest for television (14.4% BID; 14.5% non-BID). Health intervention strategies for college women should market to parents and teach recognition of credible internet sources of health information.


X-ray diagnosis of flat type mucosal carcinoma of the stomach.
The mucosal pattern of the associated IIb on double contrast images was analyzed in order to define the characteristics of minimal cancer invasion. The mucosal surface of the IIb lesion presents an irregular outlined, uneven sized nodular pattern frequently associated with tiny erosions or superficial destructive changes. These minute and delicate abnormalities are demonstrated only on high quality double contrast images. Three typical cases are presented.


Modeling of dielectric properties of complex fluids with an equation of state.
The static permittivity is a key property for describing solutions containing polar and hydrogen bonding compounds. However, the precise relationship between the molecular and dielectric properties is not well-established. Here we show that the relative permittivity at zero frequency (static permittivity) can be modeled simultaneously with thermodynamic properties. The static permittivity is calculated from an extension of the framework developed by Onsager, Kirkwood, and Fröhlich to associating mixtures. The thermodynamic properties are calculated from the cubic-plus-association (CPA) equation of state that includes the Wertheim association model as formulated in the statistical associating fluid theory (SAFT) to account for hydrogen bonding molecules. We show that, by using a simple description of the geometry of the association, we may calculate the Kirkwood g-factor as a function of the probability of hydrogen bond formation. The results show that it is possible to predict the static permittivity of complex mixtures over wide temperature and pressure ranges from simple extensions of well-established theories simultaneously with the calculation of thermodynamic properties.


Effects of heavy resistance/power training on maximal strength, muscle morphology, and hormonal response patterns in 60-75-year-old men and women.
Eleven women (TRW; 64 +/- 4 yrs) and ten men (TRM; 65 +/- 5 yrs) participated in the strength/power training twice a week for 24 weeks. Basal concentrations of serum total and free testosterone, growth hormone (GH), dehydroepiandrosterone sulfate (DHEAS), cortisol and sex hormone binding globulin (SHBG) as well as acute responses of serum total and free testosterone, growth hormone (GH) were measured. Maximal 1RM strength in the squat, chair rise time and muscle fibre distribution and areas of type I and IIa and IIb of the vastus lateralis were also examined. 1RM squat increased in TRW by 26 (SD10)% (p < .001), and in TRM by 35 (7)% (p < .001) and chair rise time improved in both groups (p < .001). Fibre areas increased in type I, (p < .01), IIa (p < .01) and IIb (p < .01) in TRM and type I (p < .05) and IIa (p < .05) in TRW. The proportion of type IIa increased from 31% to 43% (p < .05) in TRW and that of type IIb decreased from 27% to 17% (p < .05) in TRW and from 25% to 17% (p < .05) in TRM. Individual concentrations of testosterone/cortisol ratios correlated (r = 0.63; p < .05) with the individual increases in 1RM strength in TRW. The exercise sessions resulted in acute increases in serum GH in both groups (p < .05) with a further increase (p < .01) up to 10 minutes post-loading in TRM at post-training.


Prospective Evaluation of a Noninvasive Hemoglobin Measurement System in Total Joint Arthroplasty.
We sought to prospectively determine the efficacy of a noninvasive hemoglobin measurement system compared to a traditional blood draw in patients undergoing total joint arthroplasty. One hundred consecutive patients had their hemoglobin level measured by blood draw and the noninvasive device, simultaneously. Results were analyzed for the entire group and further stratified based on race and perfusion index measured by the device. The financial implications and patient satisfaction were compared. Hemoglobin measurements in the entire group and the two sub-groups were similar between the noninvasive device and the traditional blood draw. The noninvasive system was preferred by 100% of patients. Additionally, cost savings per patient using the noninvasive system was $16.50. This correlated to an 86% savings per case over the standard blood draw. The noninvasive hemoglobin monitoring system offers comparable measurements to a standard blood draw, while improving patient satisfaction and lowering costs. (Journal of Surgical Orthopaedic Advances 29(2):94-98, 2020).


Report on Proceedings of the 12th Annual European CME Forum, University of Manchester, November 2019.
The 12th Annual European CME Forum (#12ECF) was held 6-8 November 2019 at the Barnes Wallis building in the University of Manchester, Manchester, UK. An international group of attendees participated in highly interactive learning sessions, ranging from workshops to panel discussions to oral presentations by poster authors. Breakout session themes addressed continuing medical education (CME) from the perspective of the learner (micro-practice); collaborations, partnerships and interprofessional approaches (meso-practice); and consideration of compliance and regulatory issues (macro-practice). Topics covered included standards for accreditation, doctor-patient communication, a framework for CME educators' professional development, capacity building and a futurist viewpoint of continuing professional development (CPD) from a global perspective. The high level of engagement by learners set a solid foundation for further collaboration among stakeholders in European CME.


Synthesis and biological activity of new potential agonists for the human adenosine A2A receptor.
New adenosine derivatives have been synthesized and tested as putative agonists of adenosine receptors. Compounds 2-6 derive from the introduction of several types of substituents (electron donating, electron withdrawing, and halogens) in the para-position of the phenyl ring of the parent compound 1, and compound 7 lacks the hydroxyl group of amino alcohol 1. In radioligand binding assays using recombinant human A(1), A(2A), A(2B), and A(3) receptors, all compounds showed very low or negligible affinity for A(1) and A(2B) receptors but compounds 3, 5, and 7 displayed a remarkably potent affinity for the A(2A) receptor with K(i) values of 1-5 nM. Bromo derivative 3 displayed a selectivity A(1)/A(2A) = 62 and A(3)/A(2A) = 16 whereas the presence of a hydroxyl group (compound 5) improved the selectivity of A(1)/A(2A) and A(3)/A(2A) to 120- and 28-fold, respectively. When the methoxy derivative 4 lacks the hydroxyl group on the side chain (compound 7), the binding affinity for A(2A) is increased to 1 nM, improving selectivity ratios to 356- and 100-fold against A(1) and A(3), respectively. In Chinese hamster ovary cells transfected with human A(2A) and A(2B) receptors, most compounds showed a remarkable activity for the A(2A) receptor, except chloro derivative 2, with EC(50) values ranging from 1.4 to 8.8 nM. The compounds behaved as good A(2A) agonists, and all were more selective than 5'-(N-ethylcarboxamino)adenosine (NECA), with A(2B)/A(2A) ratios of cAMP accumulation ranging from 48 for compound 2 to 666 for compound 7 while the corresponding A(2B)/A(2A) ratio for NECA was only 9. Compounds 1, 3, 5, and 7 also displayed higher selectivities than NECA up to 100-fold in isolated aortas of rat and guinea pig. In guinea pig tracheal rings precontracted by carbachol, compounds 2 and 4 were more potent than adenosine (100-fold) and NECA (10-fold), whereas compounds 1 and 7 displayed similar effects to NECA. Pretreatment of the tracheal rings with A(2), A(2A), and A(2B) receptor antagonists 3,7-dimethyl-l-propargylxanthine, 8-(3-chlorostyryl)caffeine, and alloxazine produced a marked inhibition of the tracheal relaxations induced by compounds 1, 2, and 4, but none of the compounds showed selectivity toward any of the adenosine receptors.


[MoS4]2--Intercalated NiCo-Layered Double Hydroxide Nanospikes: An Efficiently Synergized Material for Urine To Direct H2 Generation.
Substituting the energy-uphill water oxidation half-cell with readily oxidizable urea-rich urine, a ground-breaking bridge is constructed, combining the energy-efficient hydrogen generation and environmental protection. Hence, designing a robust multifunctional electrocatalyst is desirable for widespread implementation of this waste to fuel technology. In this context, here, we report a simple tuning of the electrocatalytically favorable characteristics of NiCo-layered double hydroxide by introducing [MoS4]2- in its interlayer space. The [MoS4]2- insertion as well as its effect on the electronic structure tuning is thoroughly studied via X-ray photoelectron spectroscopy in combination with electrochemical analysis. This insertion induces overall electronic structure tuning of the hydroxide layer in such a way that the designed catalyst exhibited favorable kinetics toward all the required reactions of hydrogen generation. This is why our homemade catalyst, when utilized both as a cathode and anode to fabricate a urea electrolyzer, required a mere ∼1.37 V cell potential to generate sufficient H2 by reaching the benchmark 10 mA cm-2 in 1 M KOH/0.33 M urea along with long-lasting catalytic efficiency. Other indispensable reason of selecting [MoS4]2- is its high-valent nature making the catalyst highly selective and insensitive to common catalyst-poisoning toxins of urine. This is experimentally supported by performing the real urine electrolysis, where the nanospike-covered Ni foam-based catalyst showed a performance similar to that of synthetic urea, offering its industrial value. Other intuition of selecting [MoS4]2- was to provide a ligand-based mechanism for hydrogen evolution half-cell [hydrogen evolution reaction (HER)] to preclude the HER-competing oxygen reduction. Another crucial point of our work is its potential to avoid the mixing of two explosive product gases, that is, H2 and O2.


[Evaluation of the impact of genetic background on islet beta-cell function of normal glucose tolerance and newly diagnosed diabetic patients by L-arginine stimulation test.].
To explore the impact of genetic background on pancreatic beta-cell first-phase secretion function with L-arginine (L-ARG) stimulation test. Plasma insulin level was detected in 201 cases before and after L-ARG stimulation test. Among them, 61 cases were newly diagnosed type 2 diabetic patients with family history of diabetes (FH+DM), 55 newly diagnosed type 2 diabetic patients without family history of diabetes (FH-DM), 31 with normal glucose tolerance and family history of diabetes (FH+) 54 with normal glucose tolerance but without family history of diabetes (FH-). Homeostasis model assessment (HOMA) was used to estimate insulin resistance (HOMA-IR). It was premised that gender, age and BMI were similar among the 4 groups. (1) TC, TG, fasting plasma glucose, 2h plasma glucose, fasting insulin and HOMA-IR in the two groups of newly diagnosed type 2 diabetic patients with or without family history of diabetes were significantly higher than those in the two groups of normal glucose tolerance with or without family history of diabetes. The multiples of the peak level and the base level of insulin secretion in the groups of newly diagnosed diabetes were significantly lower than those in the groups of normal glucose tolerance with and without family history (P < 0.05). (2) Insulin secretion reached a peak in 2 minutes and started to decline in 4 minutes in all the four groups. (3) The multiples of the peak level and the base level of insulin secretion in normal glucose tolerance group with family history of diabetes were 20.8% lower than those in the group without family history, being 7.27 and 9.18 respectively (P < 0.05). (4) Two-minute peak insulin secretion, HOMA-IR and age in the newly diagnosed type 2 diabetic group with family history of diabetes was significantly lower than these in the group without family history (P < 0.05). The multiples of the peak level and the base level of insulin secretion in the newly diagnosed type 2 diabetic group with family history of diabetes and that group without family history were 5.18 and 5.31 respectively and there was no significant difference between the two groups (P > 0.05). (5) When the normal glucose tolerance subjects with family history of diabetes progressed to suffer from diabetes, the multiples of the peak level and the base level of insulin secretion declined 43.6% (P < 0.05) more than those in the subjects still with normal glucose tolerance without family history. In the early course of diabetes, insulin resistance dose not function significantly, but genetic background make the first-phase secretory function of the beta-cell to decline gradually and type 2 diabetes occurs easily. In the absence of genetic background, insulin resistance makes first-phase the secretion of insulin to decline relatively slow.


Can Contrast-Enhanced Multi-Detector Computed Tomography Replace Transesophageal Echocardiography for the Detection of Thrombogenic Milieu and Thrombi in the Left Atrial Appendage: A Prospective Study with 124 Patients.
To assess the diagnostic value of contrast-enhanced multi-detector computed tomography (MD-CT) for identifying patients with left atrial appendage (LAA) thrombus or circulatory stasis. 124 patients with a history of atrial fibrillation and/or cerebral ischemia (83 men, mean age 58.6 ± 12.4 years) and with a clinical indication for MD-CT of the heart and for transesophageal echocardiography (TEE) were included in the study. LAA thrombus or thrombogenic milieu was visually identified in TEE and MD-CT. In addition, MD-CT was analyzed quantitatively measuring the Hounsfield units (HU) of the left atrium (LA), the LAA and the ascending aorta (AA), and calculating the HU ratios LAA/AA (HU [LAA/AA]) und LAA/LA (HU [LAA/LA]). Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated. The prevalence of a thrombus or thrombogenic milieu as assessed by TEE was 21.8 %. The HU ratio was lower in patients with thrombus or thrombogenic milieu (HU [LAA/AA]: 0.590 ± 0.248 vs. 0.909 ± 0.141; p < 0.001 und HU [LAA/LA] 0.689 ± 0.366 vs. 1.082 ± 0.228; p < 0.001). For the diagnosis of thrombus or a thrombogenic milieu, visual analysis yielded a sensitivity of 81.5 %, a specificity of 96.9 %, a PPV of 87.5 % and a NPV of 95.2 %. By combining visual and quantitative analysis with one criterion being positive, the specificity decreased to 91.8 %, the sensitivity to 77.8 %, the PPV to 72.4 %, and the NPV to 94.9 %. Visual analysis of the LAA in the evaluation of thrombus or thrombogenic milieu yields a high NPV of 95.1 % and may especially be useful to rule out LAA thrombi in patients with contraindications for TEE. Additional calculation of HU ratios did not improve the diagnostic performance of MD-CT. • MD-CT can reliably exclude atrial appendage thrombi/thrombogenic milieu. • MD-CT is an alternative method in patients with contraindications to TEE. • Calculation of relative HU ratios does not improve the diagnostic value of MD-CT.


Autologous blood stem cell harvesting and transplantation in patients with advanced ovarian cancer.
We investigated the feasibility of a programme of autologous blood stem cell (ABSC) harvesting and transplantation in 13 patients with advanced ovarian cancer, previously untreated by chemotherapy or radiotherapy and entering a phase II study of high-dose cisplatin, etoposide and carboplatin with haematopoietic stem cell rescue. Prior to high-dose treatment all patients underwent two courses of cisplatin and cyclophosphamide. An 8-fold increase of the peripheral colony forming unit granulocytic-macrophage (CFU-GM) was observed during recovery from myelosuppression after the first chemotherapy course. The second course determined a 2.5-fold increase of peripheral CFU-GM. In 70% of enrolled patients (nine patients) we were able to perform ABSC harvesting by leukaphereses; in the apheresed patients we harvested an average of 20.8 x 10(4)/kg CFU-GM (range 10.9-37.0). Haematopoietic trilineage engraftment, established as the number of days necessary to reach white blood cells (WBC) greater than 1.0 x 10(9)/l, polymorphonuclear leucocytes (PMN) greater than 0.5 x 10(9)/l and platelets (PLT) greater than 50 x 10(9)/l, occurred very promptly and was sustained in the same series after high-dose cisplatin, carboplatin and etoposide, followed by autologous blood stem cell transplantation (ABSCT). In our experience we found a significant correlation (r = 0.77; P less than 0.05) between CFU-GM infused dose and the engraftment speed of PMN. We conclude that the combination of cisplatin and cyclophosphamide is effective in mobilizing haematopoietic progenitors in the peripheral blood of patients with advanced ovarian cancer, previously untreated by chemoradiotherapy. Moreover, ABSCT is capable of rapidly restoring the haematopoietic function after high-dose treatment and for this reason it represents a particularly advisable therapeutic option for the treatment of solid tumours because these patients are commonly older than 50 and can be excluded from bone marrow transplantation.


The effect of CYP2D6 polymorphisms on dextromethorphan metabolism in Mexican Americans.
CYP2D6 is one of the most polymorphic of the cytochrome P450 enzymes. Genetic differences in this enzyme have been reported in whites, blacks, and Asians. However, there is very little information about polymorphisms of this enzyme in Mexican Americans. The objectives of the present study were to assess the metabolic activity of CYP2D6 in a Mexican American population using dextromethorphan and to correlate this metabolic activity with a genotypic analysis. The sample consisted of 50 Mexican American subjects and 25 non-Mexican American controls. Overnight urine samples were collected and analyzed by high-performance liquid chromatography to calculate the metabolic ratio of dextromethorphan to dextrorphan. Blood samples were collected for genotypic analysis of CYP2D6 alleles. The frequency of the poor metabolizer phenotype was the same in the Mexican American group and the non-Mexican American group (6% vs 5.5%). The frequency of alleles in the Mexican American group was similar to frequencies published in other reports for non-Hispanic whites: *4 = 0.17, *5 = 0.02, *10 = 0.01, *17 = 0.02, *xN = 0.03. These results indicate that compared with non-Hispanic whites, Mexican Americans have a similar proportion of poor metabolizer phenotype and similar genetic polymorphisms of CYP2D6.


International aid and natural disasters: a pre- and post-earthquake longitudinal study of the healthcare infrastructure in Leogane, Haiti.
The reconstruction of healthcare systems in developing countries after natural disasters is poorly understood. Using data collected before and after the 2010 Haiti earthquake, we detail the response of aid agencies and their interaction with local healthcare providers in Leogane, the city closest to the epicenter. We find that the period after the earthquake was associated with an increase in the total number of healthcare facilities, inpatient beds, and surgical facilities and that international aid has been a driving force behind this recovery. Aid has funded 12 of 13 new healthcare facilities that have opened since the earthquake as well as the reconstruction of 7 of 8 healthcare facilities that have been rebuilt. Despite increases in free, aid-financed healthcare, private Haitian healthcare facilities have remained at a constant number. The planned phase-out of several aid-financed facilities, however, will leave Leogane with fewer inpatient beds and healthcare services compared with the pre-earthquake period.


Metabolism of the food-borne mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in humans.
The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was investigated in five human volunteers given a dietary equivalent of 14C-labeled MeIQx. The amount of the dose excreted in urine ranged from 20.2% to 58.6%, with unmetabolized MeIQx accounting for 0.7-2.8% of the dose. Five principal metabolites were detected in urine, and four of the derivatives were characterized by on-line UV spectroscopy and by HPLC-MS following immunoaffinity chromatography. Two metabolites were identified as the phase II conjugates N2-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl)sulfamic acid (MeIQx-N2-SO3(-)) and N2-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f ]quinoxaline (MeIQx-N2-Gl). Two other metabolites were the cytochrome P450-mediated (P450) oxidation products 2-amino-8-(hydroxymethyl)-3-methylimidazo[4,5-f]quinoxaline (8-CH2OH-MeIQx), and N2-(beta-1-glucosiduronyl)-N-hydroxy-2-amino-3,8-dimethylimidaz o[4,5-f]quinoxaline (NOH-MeIQx-N2-Gl). The latter product is a conjugate of the genotoxic metabolite 2-(hydroxyamino)-3,8-dimethylimidazo-[4,5-f]quinoxaline (NHOH-MeIQx). A large interindividual variation was observed in the metabolism and disposition of MeIQx; these four metabolites and unchanged MeIQx combined accounted for 6.3-26.7% of the total dose. The remaining principal metabolite found in all subjects accounted for 7.6-28% of the dose. It has not been previously identified in rodents or nonhuman primates, and its structure remains unknown. P450-mediated ring oxidation of MeIQx at the C-5 position, a major pathway of detoxication in rodents, was not detected in humans. Both 8-CH2OH-MeIQx formation and NHOH-MeIQx formation are catalyzed by P450 1A2 and may be useful biomarkers of P450 1A2 activity in humans. The levels of NHOH-MeIQx-N2-Gl found in human urine ranged from 1.4% to 10.0% of the dose, which is significantly higher than that formed in rodents and nonhuman primates undergoing cancer bioassays. Thus, bioactivation of MeIQx by P450-mediated N-oxidation is extensive in humans.


Familiarity and older adults' transcriptions of native and nonnative speech.
24 adults ages 60+ yr. transcribed 60 words and 30 sentences spoken by native speakers of English, Taiwanese, and Spanish to assess whether familiarity with the nonnative English speakers' accents improved transcription scores. The accuracy of listeners' transcription scores on the first half of the stimulus items was compared with accuracy of listeners' scores on the second half. Analysis indicated accuracy of transcriptions declined on words but improved for sentences, so familiarity and length of the stimuli may influence listeners' accurate transcribing of accented speech.


A study of the characteristics of karst groundwater circulation based on multi-isotope approach in the Liulin spring area, North China.
Due to the significance of karst groundwater for water supply in arid and semi-arid regions, the characteristics of the karst groundwater flow system in the Liulin spring area, North China, are analysed through isotopic tracing (δ(2)H, δ(18)O, δ(13)C and (3)H) and dating approaches ((14)C). The results show that the primary recharge source of karst groundwater is precipitation. Evaporation during dropping and infiltration of rainfall results in a certain offset in the values of δ(2)H and δ(18)O in groundwater samples from the global meteoric water line (GMWL) and the local meteoric water line (LMWL). The altitudes of the recharge region calculated by δ(18)O range from 1280 to 2020 m above sea level, which is consistent with the altitudes of the recharge area. The Liulin spring groups could be regarded as the mixing of groundwater with long and short flow paths at a ratio of 4:1. In the upgradient of the Liulin spring, the groundwater represents modern groundwater features and its [Formula: see text] is mainly derived from dissolution of soil CO(2), while in the downgradient of the Liulin spring, the (14)C age of dissolved inorganic carbon (DIC) in groundwater shows an apparent increase and [Formula: see text] is mainly derived from the dissolution of carbonate rocks. The mean flow rate calculated by (14)C ages of DIC between IS10 and IS12 is 1.23 m/year.


Galectin-3 and β-catenin are associated with a poor prognosis in serous epithelial ovarian cancer.
This study was designed to explore the expression levels of Galectin-3 (Gal-3) and β-catenin in serous epithelial ovarian cancer (SEOC), the linkage between their expressions, and the clinicopathological features of SEOC patients. Seventy-four SEOC patients' specimens were detected for Gal-3 and β-Catenin expressions using immunohistochemistry, and the association between β-catenin or Gal-3 protein expressions and clinicopathological features, treatment effects, and prognosis were analyzed using SPSS 19.0. Western blot was used to analyze protein expressions of Wnt/β-catenin pathway in ovarian cancer cell lines. There was a statistically significant positive correlation between Gal-3 and β-catenin expressions in SEOC (r=0.304 and P=0.001). Gal-3 expression was related to the grade (P=0.037), clinical stage (P=0.034), platinum resistance (P=0.030), and recurrence (P=0.001) in SEOC. There was a significant correlation between β-catenin with recurrence in SEOC (P=0.035). Platinum resistance (P=0.003) and Gal-3 expression (P<0.001) were independent risk factors for poorer overall survival (OS). OS of the strongly positive Gal-3 group was significantly lower than that of the negative and weakly positive groups (log-rank test, P=0.001). OS of the positive β-catenin group was lower than that of the negative β-catenin group (log-rank test, P=0.034). Downregulating Gal-3 expression attenuated the protein expressions of Wnt/β-catenin pathway in ovarian cancer cell lines. Gal-3 might activate Wnt/β-catenin signaling pathway in SEOC. Hence, Gal-3 may serve as a prognostic factor for SEOC. Targeting Gal-3 may be a promising new treatment approach for SEOC.


Synaptic acetylcholinesterase of chicken muscle changes during development from a hybrid to a homogeneous enzyme.
The asymmetric (20S) form of acetylcholinesterase (AChE) in 1-day-old chick muscle is a hybrid enzyme containing both AChE (110 kd) and butyrylcholinesterase (BuChE, 72 kd) catalytic subunits. However, we now report that the asymmetric AChE extracted or immunopurified from older adult chicken muscles, where it is the endplate form, shows a progressive developmental loss of the BuChE subunit and its activities, centred around 4 weeks of age, while the AChE and collagenous subunits remain. In confirmation, using differential labelling and co-sedimentation it was shown that the hybrid 20S AChE/BuChE form of 1-day chick muscle is gradually and completely replaced during muscle maturation by a 21.3S form, also collagen-tailed but otherwise homogeneous in AChE catalytic subunits. Two other changes occur concomitantly. Firstly, the AChE catalytic subunit of the adult form has a lower apparent mol. wt in gel electrophoresis, by 5 kd, than the same subunit in the 1-day hybrid enzyme; this difference does not reside in the carbohydrate attachments. Secondly, the collagen tail changes, in that some conformation-dependent epitopes on it disappear in the same period. Hence, a major reorganization of the asymmetric AChE, involving all three types of subunit, occurs in the course of muscle development.


A comparative analysis of cell-type adjustment methods for epigenome-wide association studies based on simulated and real data sets.
Technological advances and reduced costs of high-density methylation arrays have led to an increasing number of association studies on the possible relationship between human disease and epigenetic variability. DNA samples from peripheral blood or other tissue types are analyzed in epigenome-wide association studies (EWAS) to detect methylation differences related to a particular phenotype. Since information on the cell-type composition of the sample is generally not available and methylation profiles are cell-type specific, statistical methods have been developed for adjustment of cell-type heterogeneity in EWAS. In this study we systematically compared five popular adjustment methods: the factored spectrally transformed linear mixed model (FaST-LMM-EWASher), the sparse principal component analysis algorithm ReFACTor, surrogate variable analysis (SVA), independent SVA (ISVA) and an optimized version of SVA (SmartSVA). We used real data and applied a multilayered simulation framework to assess the type I error rate, the statistical power and the quality of estimated methylation differences according to major study characteristics. While all five adjustment methods improved false-positive rates compared with unadjusted analyses, FaST-LMM-EWASher resulted in the lowest type I error rate at the expense of low statistical power. SVA efficiently corrected for cell-type heterogeneity in EWAS up to 200 cases and 200 controls, but did not control type I error rates in larger studies. Results based on real data sets confirmed simulation findings with the strongest control of type I error rates by FaST-LMM-EWASher and SmartSVA. Overall, ReFACTor, ISVA and SmartSVA showed the best comparable statistical power, quality of estimated methylation differences and runtime.


Utilizing the Hofmeister Effect to Induce Hydrogelation of Nonionic Supramolecular Polymers into a Therapeutic Depot.
Nonionic hydrogels are of particular interest for long-term therapeutic implantation due to their minimal immunogenicity relative to their charged counterparts. However, in situ formation of nonionic supramolecular hydrogels under physiological conditions has been a challenging task. In this context, we report on our discovery of salt-triggered hydrogelation of nonionic supramolecular polymers (SPs) formed by self-assembling prodrug hydrogelators (SAPHs) through the Hofmeister effect. The designed SAPHs consist of two SN-38 units, which is an active metabolite of the anticancer drug irinotecan, and a short peptide grafted with two or four oligoethylene glycol (OEG) segments. Upon self-assembly in water, the resultant nonionic SPs can be triggered to gel upon addition of phosphate salts. Our 1 H NMR studies revealed that the added phosphates led to a change in the chemical shift of the methylene protons, suggestive of a disruption of the water-ether hydrogen bonds and consequent reorganization of the hydration shell surrounding the SPs. This deshielding effect, commensurate with the amount of salt added, likely promoted associative interactions among the SAPH filaments to percolate into a 3D network. The formed hydrogels exhibited a sustained release profile of SN-38 hydrogelator that acted potently against cancer cells.


Pathogenic free-living amoebic encephalitis in Japan.
Over 600 cases of amoebic encephalitis caused by pathogenic free-living amoebas (Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri) have been reported worldwide, and in Japan, 24 cases have been reported from the first case in 1976 up to 2018. Among these cases, 18 were caused by B. mandrillaris, four by Acanthamoeba spp., one by N. fowleri, and one was of unknown etiology. Additionally, eight cases were diagnosed with encephalitis due to pathogenic free-living amoebas before death, but only three cases were successfully treated. Unfortunately, all other cases were diagnosed by autopsy. These facts indicate that an adequate diagnosis is difficult, because encephalitis due to pathogenic free-living amoebas does not show typical symptoms or laboratory findings. Moreover, because the number of cases is limited, other cases might have been missed outside of those diagnosed by autopsy. Cases of encephalitis caused by B. mandrillaris have been reported from all over Japan, with B. mandrillaris recently isolated from soil in Aomori prefecture. Therefore, encephalitis caused by pathogenic free-living amoebas should be added to the differential diagnosis of encephalitis patients.


Melting Behavior of Alkaline-Earth Metal Carbodiimides and Their Thermochemistry from First-Principles.
We present a combined experimental and theoretical investigation targeted at the thermochemical properties of a series of alkaline-earth metal carbodiimides. Their Gibbs energies and decomposition temperatures were calculated on the basis of phonons derived from density functional theory. The theoretical decomposition temperatures arrive at 1270, 1224, and 1185 K for CaNCN, α-SrNCN, and tetragonal BaNCN, respectively. Only the melt of tetragonal BaNCN is maintained at ∼1173 K, which is slightly below its calculated decomposition temperature. Experimentally, the melt of BaNCN did not decompose below 1273 K. On the contrary, both CaNCN and α-SrNCN partially decompose by forming a mixture of their carbides, metals, and nitrogen. The calculated Gibbs energies also show that the tetragonal phase of BaNCN is more stable than the rhombohedral one. We conclude that the melt of BaNCN is useful in the crystal growth of oxynitride perovskites such as BaTaO2N.


Not straightforward: modelling non-linearity in training load and injury research.
To determine whether the relationship between training load and injury risk is non-linear and investigate ways of handling non-linearity. We analysed daily training load and injury data from three cohorts: Norwegian elite U-19 football (n=81, 55% male, mean age 17 years (SD 1)), Norwegian Premier League football (n=36, 100% male, mean age 26 years (SD 4)) and elite youth handball (n=205, 36% male, mean age 17 years (SD 1)). The relationship between session rating of perceived exertion (sRPE) and probability of injury was estimated with restricted cubic splines in mixed-effects logistic regression models. Simulations were carried out to compare the ability of seven methods to model non-linear relationships, using visualisations, root-mean-squared error and coverage of prediction intervals as performance metrics. No relationships were identified in the football cohorts; however, a J-shaped relationship was found between sRPE and the probability of injury on the same day for elite youth handball players (p<0.001). In the simulations, the only methods capable of non-linear modelling relationships were the quadratic model, fractional polynomials and restricted cubic splines. The relationship between training load and injury risk should be assumed to be non-linear. Future research should apply appropriate methods to account for non-linearity, such as fractional polynomials or restricted cubic splines. We propose a guide for which method(s) to use in a range of different situations.