Spectral and Angle-Resolved Magneto-Optical Characterization of Photonic Nanostructures.
Photonic crystals are periodic nanostructures that can support a variety of confined electromagnetic modes. Such confined modes are usually accompanied by local enhancement of electric field intensity that strengthens light-matter interactions, enabling applications such as surface-enhanced Raman scattering (SERS) and surface plasmon enhanced sensing. In the presence of magneto-optically active materials, the local field enhancement gives rise to anomalous magneto-optical activity. Typically, the confined modes of a given photonic crystal depend strongly on the wavelength and incidence angle of the incident electromagnetic radiation. Thus, spectral and angular-resolved measurements are needed to fully identify them as well as to establish their relationship with the magneto-optical activity of the crystal. In this article, we describe how to use a Fourier-plane (back focal plane) microscope to characterize magneto-optically active samples. As a model system, here we use a plasmonic grating built out of magneto-optically active Au/Co/Au multilayer. In the experiments, we apply a magnetic field on the grating in situ and measure its reciprocal space response, obtaining the magneto-optical response of the grating over a range of wavelengths and incident angles. This information enables us to build a complete map of the plasmonic band structure of the grating and the angle and wavelength dependent magneto-optical activity. These two images allow us to pinpoint the effect that the plasmon resonances have on the magneto-optical response of the grating. The relatively small magnitude of magneto-optical effects requires a careful treatment of the acquired optical signals. To this end, an image processing protocol for obtaining magneto-optical response from the acquired raw data is laid out.


Migration stopover ecology of Cinnamon Teal in western North America.
Identifying migration routes and fall stopover sites of Cinnamon Teal (Spatula cyanoptera septentrionalium) can provide a spatial guide to management and conservation efforts, and address vulnerabilities in wetland networks that support migratory waterbirds. Using high spatiotemporal resolution GPS-GSM transmitters, we analyzed 61 fall migration tracks across western North America during our three-year study (2017-2019). We marked Cinnamon Teal primarily during spring/summer in important breeding and molting regions across seven states (California, Oregon, Washington, Idaho, Utah, Colorado, and Nevada). We assessed fall migration routes and timing, detected 186 fall stopover sites, and identified specific North American ecoregions where sites were located. We classified underlying land cover for each stopover site and measured habitat selection for 12 land cover types within each ecoregion. Cinnamon Teal selected a variety of flooded habitats including natural, riparian, tidal, and managed wetlands; wet agriculture (including irrigation ditches, flooded fields, and stock ponds); wastewater sites; and golf and urban ponds. Wet agriculture was the most used habitat type (29.8% of stopover locations), and over 72% of stopover locations were on private land. Relatively scarce habitats such as wastewater ponds, tidal marsh, and golf and urban ponds were highly selected in specific ecoregions. In contrast, dry non-habitat across all ecoregions, and dry agriculture in the Cold Deserts and Mediterranean California ecoregions, was consistently avoided. Resources used by Cinnamon Teal often reflected wetland availability across the west and emphasize their adaptability to dynamic resource conditions in arid landscapes. Our results provide much needed information on spatial and temporal resource use by Cinnamon Teal during migration and indicate important wetland habitats for migrating waterfowl in the western United States.


Cholesterol and triglyceride concentrations in lipoproteins as related to carotid intima-media thickness.
Since distinct cholesterol and triglyceride concentrations in major lipoproteins and their subclasses may be related to atherosclerosis, we investigated the relationship of cholesterol and triglyceride concentrations in lipoprotein subclasses and the severity of carotid intima-media thickness (IMT), a surrogate marker of subclinical atherosclerosis. We studied 116 apparently healthy Japanese men (53 ± 9 years) without a history of cardiovascular diseases who were not taking any medication. Carotid IMT was measured by means of high-resolution vascular ultrasound. Plasma cholesterol and triglyceride concentrations in major lipoproteins and their subclasses were determined by HPLC with gel permeation columns. By univariate analyses, carotid IMT was the most closely related to age (r = 0.528, P < 0.001), followed by smoking habit expressed as pack-year cigarette consumption (r = 0.409, P < 0.001). In addition to total cholesterol and LDL cholesterol, carotid IMT was significantly associated with cholesterol and triglyceride concentrations in several LDL and VLDL subclasses. Stepwise multiple linear regression analysis revealed that age (β = 0.436, P < 0.001), smoking (pack-years) (β = 0.225, P = 0.007), and large LDL cholesterol (β = 0.175, P = 0.023) were independent predictors of determining carotid IMT (adjusted R(2) = 0.347, P < 0.001). These results indicate that large LDL cholesterol is an important, independent determinant of carotid IMT in healthy men.


Radioimmunoassay for phencyclidine.
A sensitive and specific radioimmunoassay has been developed for the drug phencyclidine (PCP). Levels as low as 50 pg (200 femto-moles) of PCP can be detected. The specificity of the antisera has been investigated by inhibiting the [3H]PCP-anti PCP reaction with the parent drug, metabolites, and other related compounds. Three urinary metabolites, 4-phenyl-4-piperidinocyclohexanol, 1-(1-phenylcyclohexyl)-4-hydroxypiperidine and 1-phenylcyclohexylamine inhibit 2,5, and 0.002% as effectively as PCP respectively. Plasma samples supplemented with PCP (1.2 to 10,000 ng/ml) can be analyzed directly by this procedure.


The correlation of histologic features with a panoramic radiography pattern and a computed tomography pattern of bone destruction in carcinoma of the mandibular gingiva.
We sought to clarify the correlation among a computed tomography (CT) or a panoramic radiography (PR) pattern of bone destruction, a histologic pattern of bone destruction, and a mode of invasion in carcinoma of the mandibular gingiva. CT images, panoramic radiographs, and decalcified, hematoxylin-eosin-stained preparations of the excised mandibular bone of 62 patients with carcinoma of the mandibular gingiva were retrospectively evaluated. Each computed tomograph, panoramic radiograph, and the histologic pattern of bone destruction was classified as 1 of 5 types: erosive, erosive and partly mixed, mixed, mixed and partly invasive, or invasive. The mode of invasion of the tumor was also assessed with a hematoxylin-eosin-stained preparation of the initial biopsy specimen. The relationships among the CT pattern, the PR pattern, the histologic pattern of bone destruction, and the mode of invasion of the tumor were statistically analyzed by using the Spearman rank correlation test. The CT pattern (P =.005) and the PR pattern (P =.003) were significantly correlated with the histologic pattern with respect to the bone destruction. The CT pattern (P =.996), the PR pattern (P =.997), and the histologic pattern (P =.521) of bone destruction were not correlated with the mode of invasion seen in the biopsy specimen. The CT pattern and the PR pattern of bone destruction reflect the histologic pattern of bone destruction caused by carcinoma of the mandibular gingiva but are not associated with the mode of invasion of the tumor.


Effectiveness of Faradic and Russian currents on plantar flexor muscle spasticity, ankle motor recovery, and functional gait in stroke patients.
Spasticity is a major disabling symptom in patients post stroke. Though studies have demonstrated that electrical stimulation (ES) can reduce spasticity and improve passive ankle range of motion (ROM), not many studies have evaluated the effectiveness of ES on active ankle ROM. The purpose of this study was to determine the effectiveness of Faradic and Russian currents in the reduction of ankle plantar-flexor spasticity and improving motor recovery in patients post stroke. Eighty-three patients (29 females and 54 males; mean age of 57.12 years) were randomly assigned to Group 1 (task-oriented exercises), Group 2 (Faradic current for 10 min and task-oriented exercises), and Group 3 (Russian current for 10 min and task-oriented exercises) for a period of 5 sessions per week for 6 weeks. All patients were assessed for soleus and gastrocnemius muscles spasticity measured by modified modified Ashworth scale; active and passive range ROM measured by goniometer; and functional ambulation measured by modified Emory Functional Ambulation Profile at the time of recruitment to study and after 6 weeks. Both the types of stimulation and exercises were not associated with improvements in modified Emory Functional Ambulation Profile (p > 0.05). The results showed that all the groups are effective in improving passive ankle ROM (p < 0.05) and reducing soleus and gastrocnemius muscles spasticity (p < 0.05). Though all the groups were effective in improving active ankle ROM, no group was found to be superior to another after treatment CONCLUSION: Adding ES to exercises are associated with low to medium effect sizes (<0.5) in reducing spasticity and improving ankle ROM.


Structure Activity Relationship for Fumonisin Phytotoxicity.
Fumonisins are mycotoxins produced by a number of species of Fusarium and Aspergillus. They are polyketides that possess a linear polyol structure with two tricarballylic acid side chains and an amine moiety. Toxicity results from their inhibition of Ceramide Synthase (CerS), which perturbs sphingolipid concentrations. The tricarballylic side chains and amine group of fumonisins are key molecular features responsible for inhibiting CerS, however their individual contributions toward overall toxicity are not fully understood. We have recently reported novel, deaminated fumonisins produced by A. niger and have identified an enzyme (AnFAO) responsible for their synthesis. Here we performed a structure/function activity assay to investigate the individual contributions of the tricarballylic acid and amine toward overall fumonisin toxicity. Lemna minor was treated at 40 μM against FB1, hydrolyzed FB1 (hFB1), deaminated FB1 (FPy1), or hydrolyzed/deaminated (hFPy1). Four end points were monitored: plant dry weight, frond surface area, lipidomics, and metabolomics. Overall, hFB1 was less toxic than FB1 and FPy1 was less toxic than hFB1. hFPy1 which lacks both the amine group and tricarballylic side chains was also less toxic than FB1 and hFB1, however it was not significantly less toxic than FPy1. Lipidomic analysis showed that FB1 treatment significantly increased levels of phosphotidylcholines, ceramides, and pheophorbide A, while significantly decreasing the levels of diacylglycerides, sulfoquinovosyl diacylglycerides, and chlorophyll. Metabolomic profiling revealed a number of significantly increased compounds that were unique to FB1 treatment including phenylalanine, asymmetric dimethylarginine (ADMA), S-methylmethionine, saccharopine, and tyrosine. Conversely, citrulline, N-acetylornithine and ornithine were significantly elevated in the presence of hFB1 but not any of the other fumonisin analogues. These data provide evidence that although removal of the tricarballylic side chains significantly reduces toxicity of fumonisins, the amine functional group is a key contributor to fumonisin toxicity in L. minor and justify future toxicity studies in mammalian systems.


Extent of use of artificial intelligence & machine learning protocols in cancer diagnosis: A scoping review.
Artificial intelligence (AI) and machine learning (ML) have shown promising results in cancer diagnosis in validation tests involving retrospective patient databases. This study was aimed to explore the extent of actual use of AI/ML protocols for diagnosing cancer in prospective settings. PubMed was searched for studies reporting usage of AI/ML protocols for cancer diagnosis in prospective (clinical trial/real world) setting with the AI/ML diagnosis aiding clinical decision-making, from inception till May 17, 2021. Data pertaining to the cancer, patients and the AI/ML protocol were extracted. Comparison of AI/ML protocol diagnosis with human diagnosis was recorded. Through a post hoc analysis, data from studies describing validation of various AI/ML protocols were extracted. Only 18/960 initial hits (1.88%) utilized AI/ML protocols for diagnostic decision-making. Most protocols used artificial neural network and deep learning. AI/ML protocols were utilized for cancer screening, pre-operative diagnosis and staging and intra-operative diagnosis of surgical specimens. The reference standard for 17/18 studies was histology. AI/ML protocols were used to diagnose cancers of the colorectum, skin, uterine cervix, oral cavity, ovaries, prostate, lungs and brain. AI/ML protocols were found to improve human diagnosis, and had either similar or better performance than the human diagnosis, especially made by the less experienced clinician. Validation of AI/ML protocols was described by 223 studies of which only four studies were from India. Also there was a huge variation in the number of items used for validation. The findings of this review suggest that a meaningful translation from the validation of AI/ML protocols to their actual usage in cancer diagnosis is lacking. Development of regulatory framework specific for AI/ML usage in healthcare is essential.


Rapid assembly of photosystem I monolayers on gold electrodes.
Photosystem I (PSI) has drawn widespread interest for use in biomimetically inspired energy conversion devices upon extracting it from plants or cyanobacteria and assembling it at surfaces. Here, we demonstrate that a critically dense monolayer of spinach-derived PSI must be formed on an electrode surface to achieve optimal photocurrents, and we introduce a new method for preparing these dense PSI monolayers that reduces the time required for assembly by approximately 80-fold in comparison to that for adsorption from solution. This method consists of applying a vacuum above the aqueous PSI solution during assembly to concentrate PSI and precipitate it into a thick layer onto the surface of various self-assembled monolayers or directly onto the electrode surface. Rinsing with water yields a dense monolayer of PSI that draws approximately 100 nA/cm2 of light-induced current from the gold electrode in the presence of appropriate mediators.


Submonolayer Uniformity of Type II InAs/GaInSb W-shaped Quantum Wells Probed by Full-Wafer Photoluminescence Mapping in the Mid-infrared Spectral Range.
The spatial uniformity of GaSb- and InAs substrate-based structures containing type II quantum wells was probed by means of large-scale photoluminescence (PL) mapping realized utilizing a Fourier transform infrared spectrometer. The active region was designed and grown in a form of a W-shaped structure with InAs and GaInSb layers for confinement of electrons and holes, respectively. The PL spectra were recorded over the entire 2-in. wafers, and the parameters extracted from each spectrum, such as PL peak energy position, its linewidth and integrated intensity, were collected in a form of two-dimensional spatial maps. Throughout the analysis of these maps, the wafers' homogeneity and precision of the growth procedure were investigated. A very small variation of PL peak energy over the wafer indicates InAs quantum well width fluctuation of only a fraction of a monolayer and hence extraordinary thickness accuracy, a conclusion further supported by high uniformity of both the emission intensity and PL linewidth.


A novel homeobox gene mediates the Dpp signal to establish functional specificity within target cells.
Morphogen gradients of secreted molecules play critical roles in the establishment of the spatial pattern of gene expression. During midgut development in Drosophila, secreted molecules of Decapentaplegic (Dpp) and Wingless (Wg) establish unique transcriptional regulation within target cells to specify the resultant cell types. Here we report the identification of a novel homeobox gene, defective proventriculus (dve), which is required for the midgut specification under the control of Dpp and Wg. In dve mutants, two distinct parts of the midgut, the proventriculus and middle midgut, are abnormally organized. The Wg signal regulates dve expression during proventriculus development. On the other hand, dve is a downstream target of Dpp in the middle midgut and defines the functional specificity of copper cells along with another Dpp target gene, labial. Thus, the dve gene acts under the two distinct extracellular signals at distant parts of the midgut primordia.


Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer.
The toxicity and effectivity of intravenous paclitaxel and cisplatin as neoadjuvant chemotherapy were assessed in cervical cancer patients. Patients and methods. Forty-three consecutive patients affected by International Federation of Gynecology and Obstetrics (FIGO) stage IB2 to IIB were treated with paclitaxel 60 mg/m(2) that was administered intravenously over a 3-h period, followed by cisplatin 60 mg/m(2), also administered intravenously. The chemotherapy was administered every 10 days and for three courses. The toxicity of the regimen in each cycle was determined according to the WHO toxicity criteria and in cases with grade 3 or 4 toxicity, chemotherapy was postponed until the toxicity was disappeared. Before the neoadjuvant chemotherapy, the lesion was pathologically confirmed by punch biopsy, and the size of the tumor mass was measured by pelvic examination and pelvic magnetic resonance imaging (MRI). The response to the treatment was determined 10 days after three cycles of chemotherapy by pelvic examination and pelvic MRI. Two weeks after the neoadjuvant chemotherapy was completed, the patients were either given an operation or radiation therapy, depending on their overall condition, the operational risks, and personal willingness for an operation. A total of 43 patients were enrolled in this study and all of them were given an operation. Hematologic toxicity was seen in 17 patients. But most of them were anemia and there was no grade 3 or 4. Grade 1 neurotoxicities developed in 29 patients and all of them were peripheral neurotoxicity. Clinical responses occurred in 90.7% (39/43) of patients, including 39.5% (17/43) with a complete response (CR), 11.6% (5/43) with a pathologically determined complete response, 51.2% (22/43) with a partial response (PR), and 9.3% (4/43) showed stable disease (ST). A down-staging response was seen in 72.1% (31/43) of those patients showing a response. The combination of paclitaxel with cisplatin for use in neoadjuvnant chemotherapy seems to be tolerated and very active in cervical cancer. Especially, every 10 days treatment did not delay the optimal time of main treatment. A larger number of cases need to be studied to confirm the efficacy of the treatment.


What has comprehensive HIV/AIDS knowledge got to do with HIV testing among men in Kenya and Mozambique? Evidence from Demographic and Health Surveys.
People living with undiagnosed HIV are big contributors to the transmission of the virus. Although measures have been made to scale up HIV prevention and voluntary counselling and testing in sub-Saharan Africa, testing coverage remains low in many sub-Saharan African countries, including Mozambique and Kenya, where most people live with HIV/AIDS. Studies have shown that, in most countries in sub-Saharan Africa, men are less likely to test for HIV compared with women. This study examined the relationship between comprehensive HIV/AIDS knowledge and HIV testing among men in Kenya and Mozambique. Data were from the men's re-code file of the Demographic and Health Surveys of Mozambique and Kenya. Binary logistic regression models were generated and the results presented as crude odds ratios (cOR) and adjusted odds ratios (aOR). The prevalences of HIV testing in Kenya and Mozambique were 80.1% and 46.7%, respectively. Men in Mozambique who had comprehensive HIV/AIDS knowledge (aOR=1.26, CI: 1.07-1.47) were more likely to test for HIV compared with their counterparts who had no comprehensive HIV/AIDS knowledge. In Kenya, men who had comprehensive HIV/AIDS knowledge (aOR=1.23, CI: 1.09-1.39) were more likely to test for HIV compared with their counterparts who had no comprehensive HIV/AIDS knowledge. This study found a statistically strong significant association between comprehensive HIV/AIDS knowledge and HIV testing among men in Kenya and Mozambique. To improve HIV testing rate among men, it is important that interventions are geared towards improving men's comprehensive HIV/AIDS knowledge, perhaps by expanding HIV/AIDS education programmes and campaigns. This could improve HIV testing rates and ensure the realization of the global HIV/AIDS target of 95-95-95 by the year 2030.


The antipsychotic agent quetiapine is increasingly not used as such: dispensed prescriptions in Norway 2004-2015.
The antipsychotic agent quetiapine was introduced in Norway in 2003. We have assessed changes in dispensed prescriptions, including dosing, of quetiapine in Norway from 2004 to 2015. Data on the sales of antipsychotics and antidepressants were drawn from the Norwegian Prescription Database. A total of 47,474 outpatients filled 195,622 prescriptions of quetiapine. Reimbursement codes, use of antipsychotics or antidepressants 12 months prior to the first prescription of quetiapine and estimated mean volume used measured as defined daily doses (DDDs) per day were used as proxies for diagnoses. We conducted a regression analysis with DDD per day as a function of possible explanatory variables. The number of users filling at least two prescriptions of quetiapine per year increased from 584 in 2004 to 8506 in 2015 and the mean dose declined from 1.58 DDD per day (SD 8.00) to 0.48 DDD per day (SD 2.27). The latter is much lower than recommended for treatment of psychoses. In 2015, 60.1% of the 8506 quetiapine users did not seek reimbursement for the treatment of a major psychiatric disorder and only 2.6% of the patients were prescribed 1 DDD or more per day and reimbursed in accordance with the drug's primary indication, psychosis. A reported diagnosis of psychosis was not associated with higher quetiapine doses. In 2015, the pattern of quetiapine dispensing in Norway most likely reflects predominant off-label use. This is unsettling considering poorly documented effects in non-psychotic disorders, profound side effects, significant toxicity and growing concern regarding abuse.


Effects of streptozotocin-induced diabetes on rat liver sulfotransferase gene expression.
The effects of streptozotocin (STZ)-induced diabetes on rat hepatic hydroxysteroid sulfotransferase-a (HST-a) and aryl sulfotransferase IV (ASTIV) gene expression were characterized. Female Sprague-Dawley rats (aged approximately 55 days) were treated with increasing doses of STZ (65, 120, or 175 mg/kg ip) and killed 48 hr later. In some groups, diabetic rats were rendered normoglycemic with insulin before killing. STZ produced a dose-dependent increase in serum glucose levels and a dose-dependent suppression (of up to approximately 65%) of hepatic HST-a mRNA expression. Treatment with STZ (120 mg/kg ip) also significantly suppressed HST-a immunoreactive protein levels by approximately 31% relative to vehicle-treated controls. Reversal of STZ-induced diabetes with insulin significantly reduced the level of HST-a mRNA suppression associated with STZ treatment. The induction of diabetes with STZ (120 mg/kg ip) resulted in a approximately 63% suppression of HST-a mRNA expression, whereas insulin reversal of STZ-induced diabetes resulted in a approximately 34% suppression of HST-a mRNA levels. ASTIV mRNA levels displayed a significant level of suppression (approximately 35%) after treatment with STZ (65 mg/kg ip). However, unlike HST-a, treatment with higher doses of STZ (120 or 175 mg/kg) did not result in significant changes in ASTIV mRNA expression. These results suggest that, in mature female rats, the major hepatic sulfotransferase genes important to xenobiotic metabolism, HST-a and ASTIV, seem to be differentially regulated in response to STZ-induced diabetes. Moreover, negative regulation, possibly at the level of transcription, may be responsible for the changes in HST-a gene expression that accompany the development of STZ-induced diabetes.


A small number of early introductions seeded widespread transmission of SARS-CoV-2 in Québec, Canada.
Québec was the Canadian province most impacted by COVID-19, with 401,462 cases as of September 24th, 2021, and 11,347 deaths due mostly to a very severe first pandemic wave. In April 2020, we assembled the Coronavirus Sequencing in Québec (CoVSeQ) consortium to sequence SARS-CoV-2 genomes in Québec to track viral introduction events and transmission within the province. Using genomic epidemiology, we investigated the arrival of SARS-CoV-2 to Québec. We report 2921 high-quality SARS-CoV-2 genomes in the context of > 12,000 publicly available genomes sampled globally over the first pandemic wave (up to June 1st, 2020). By combining phylogenetic and phylodynamic analyses with epidemiological data, we quantify the number of introduction events into Québec, identify their origins, and characterize the spatiotemporal spread of the virus. Conservatively, we estimated approximately 600 independent introduction events, the majority of which happened from spring break until 2 weeks after the Canadian border closed for non-essential travel. Subsequent mass repatriations did not generate large transmission lineages (> 50 sequenced cases), likely due to mandatory quarantine measures in place at the time. Consistent with common spring break and "snowbird" destinations, most of the introductions were inferred to have originated from Europe via the Americas. Once introduced into Québec, viral lineage sizes were overdispersed, with a few lineages giving rise to most infections. Consistent with founder effects, the earliest lineages to arrive tended to spread most successfully. Fewer than 100 viral introductions arrived during spring break, of which 7-12 led to the largest transmission lineages of the first wave (accounting for 52-75% of all sequenced infections). These successful transmission lineages dispersed widely across the province. Transmission lineage size was greatly reduced after March 11th, when a quarantine order for returning travellers was enacted. While this suggests the effectiveness of early public health measures, the biggest transmission lineages had already been ignited prior to this order. Combined, our results reinforce how, in the absence of tight travel restrictions or quarantine measures, fewer than 100 viral introductions in a week can ensure the establishment of extended transmission chains.


Biomolecular events involved in anticryptococcal resistance in the brain.
We have recently shown that intracerebral (i.c.) administration of heat-killed Cryptococcus neoformans (HCN) enhances mouse resistance to a subsequent local challenge with lethal doses of viable yeast cells. Here we show that i.c. administration of HCN is also effective in significantly delaying brain colonization of mice intravenously infected with viable C. neoformans. PCR analysis revealed that interleukin 6 (IL-6) and IL-1 beta gene expression occurs in brain of HCN-treated mice but not in brains of saline-treated controls. In contrast, no differences are observed in terms of tumor necrosis factor alpha and IL-1 alpha gene transcripts, which are slightly and highly detectable, respectively, in saline-treated mice and which remain such also following HCN treatment. Furthermore, i.c. administration of exogenous IL-6 or IL-1 beta, but not tumor necrosis factor alpha, before local challenge with viable C. neoformans results in significantly reduced microbial counts in the brain and blood and in increased mouse survival. Taken together, these observations provide initial evidence that brain anticryptococcal resistance involves elicitation of a local cytokine response, involving primarily IL-6 and IL-1 beta.


Spectroscopic identification of reactive porphyrin motions.
Nuclear resonance vibrational spectroscopy (NRVS) reveals the vibrational dynamics of a Mössbauer probe nucleus. Here, (57)Fe NRVS measurements yield the complete spectrum of Fe vibrations in halide complexes of iron porphyrins. Iron porphine serves as a useful symmetric model for the more complex spectrum of asymmetric heme molecules that contribute to numerous essential biological processes. Quantitative comparison with the vibrational density of states (VDOS) predicted for the Fe atom by density functional theory calculations unambiguously identifies the correct sextet ground state in each case. These experimentally authenticated calculations then provide detailed normal mode descriptions for each observed vibration. All Fe-ligand vibrations are clearly identified despite the high symmetry of the Fe environment. Low frequency molecular distortions and acoustic lattice modes also contribute to the experimental signal. Correlation matrices compare vibrations between different molecules and yield a detailed picture of how heme vibrations evolve in response to (a) halide binding and (b) asymmetric placement of porphyrin side chains. The side chains strongly influence the energetics of heme doming motions that control Fe reactivity, which are easily observed in the experimental signal.


Cell differentiation during fruiting body formation in polysphondylium pallidum.
The spatial pattern of cellular differentiation was studied during fruiting body formation in Polysphondylium pallidum using 3 different staining methods: Calcofluor fluorescence (cellulose accumulation), neutral red (prestalk cells) and immunofluorescence (prespore cells). Neutral-red staining revealed the existence of a clear prestalk region which becomes evident during aggregation and continues throughout culmination. Immunofluorescent staining demonstrated that cells in the prestalk region gradually lose their presporeness (fluorescence) as they are transformed into differentiated stalk cells. Calcofluor staining revealed that stalk cell differentiation begins during the mid-aggregation phase and that the mode of formation of the main stalk and the side branches differs slightly in morphology. Calcofluor staining also demonstrated the development, during aggregation, of a thick cellulosic girdle with lateral tubular extensions which surround the aggregation streams. The above results are discussed in terms of our present knowledge about differentiation and morphogenesis in cellular slime moulds.


Arterial hypertension induced by femoral lengthening. A canine model.
In a canine experimental model, femora were lengthened 2.5 to 3.0 centimeters over a one-minute period. Systolic blood-pressure elevation averaged forty millimeters of mercury and diastolic blood-pressure elevation, twenty-two millimeters of mercury. The average peak arterial pressure was 193/115 millimeters of mercury. The effects of sympatholytic agents on the experimental model were tested. Alpha-adrenergic blockade by phenoxybenzamine, total-body catecholamine depletion by reserpine, and sympathetic ganglionic blockade by trimethaphan camphorsulfonate all inhibited the rise in arterial pressure, but beta-adrenergic blockade by propranolol did not. A differential spinal anesthetic with Xylocaine solution dramatically decreased the elevation in arterial pressure.


Status of sex reassignment surgery for gender identity disorder in Japan.
An incongruence between one's physiological sex and the gender identity that is one's basic sense of self as a man or a woman is known as gender identity disorder. In general, the conditions of physiological men having female gender identity and physiological women having male gender identity are called male-to-female and female-to-male gender identity disorder, respectively. Although the precise pathogenesis of gender identity disorder remains unclear, the prevalence of gender identity disorder is quite high, with the rates calculated for male-to-female to be 1:25,000 and female-to-male to be 1:12,000 in Hokkaido, Japan. The diagnosis and treatment of gender identity disorder in Japan are based on the Diagnostic and Therapeutic Guidelines for Patients with Gender Identity Disorder, 4th edition. Although gender identity disorder was previously thought to be a psychiatric condition, it is extremely difficult to assign gender identity to physiological sex by psychiatric and psychological treatments. To adapt the figure of the body to the native gender identity, physical treatments such as administration of cross-sex steroids and sex reassignment surgery are considered. However, there are very few institutions that routinely carry out sex reassignment surgery in Japan, even though it is mandatory for changing sex on the census register at the present time. Sex reassignment surgery for male-to-female and female-to-male patients includes orchiectomy, penectomy, clitoroplasty, vaginoplasty and vulvoplasty, and hysterectomy, ovariectomy, metoidioplasty and phalloplasty, respectively. To provide accurate information about physical treatment for patients with gender identity disorder, even urologists who are not actively involved in the diagnosis and treatment of gender identity disorder should understand the fundamental aspects and contemporary problems of gender identity disorder.


Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the Second REVEAL Trial.
Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Digital image analysis of rosacea facial erythema was evaluated as a secondary efficacy outcome measure. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal tolerability. Patients were followed for 28 days posttreatment to assess worsening of erythema (1-grade increase in severity from baseline on composite CEA/SSA in patients with moderate erythema at baseline; rebound effect). The study included 445 patients (mean age: 50.3 years; 78.7% female); most had moderate erythema at baseline (84.0% on CEA; 91.5% on SSA). The proportion of patients achieving the primary efficacy outcome was significantly greater with oxymetazoline versus vehicle (P=0.001). Similar results favoring oxymetazoline over vehicle were observed for the individual CEA and SSA scores (P less than 0.001 and P=0.011, respectively). Median reduction in rosacea facial erythema on day 29 as assessed by digital image analysis also favored oxymetazoline over vehicle (P less than 0.001). Safety results were similar between oxymetazoline and vehicle; discontinuations due to TEAEs were low (2.7% vs 0.5%). Following cessation of treatment, 2 (1.2%) patients in the oxymetazoline group and no patient in the vehicle group had rebound effect compared with their day 1 baseline score. Topical oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in the treatment of moderate to severe persistent facial erythema of rosacea.
J Drugs Dermatol. 2018;17(3):290-298.
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Colour stability of three esthetic laminate materials against to different staining agents.
The purpose of the present study was to evaluate the colour stability of three laminate veneer materials against to tea, coffee and cigarette smoke. 72 discs prepared by using two different type composite materials and a dental porcelain were divided into groups and immersed into distilled water, tea, Turkish coffee solutions. The last group was exposed to cigarette smoke. Colour differences were measured by colorimeter at the beginning and then in the period of 1 day, 1 week and 1 month respectively. As a result, it was found that cigarette smoke was the most staining agent, porcelain material was the most colour stable material, and indirect composite material was more colour stable than the direct one.


A method for the quantification of benzodiazepine receptors by using 123I-iomazenil and SPECT with one scan and one blood sampling.
Iodine-123-iomazenil (Iomazenil) is a ligand of central type benzodiazepine receptors for single photon emission computed tomography (SPECT). Previously we reported a simple, table look-up method for quantification of its binding potential (BP) by using two SPECT scans and calibrated standard input function with one blood sampling. This method is based on a two-compartment model (K1: influx rate constant; k2: efflux rate constant; Vd (= K1/k2): the total distribution volume corresponding BP), and requires two SPECT scans for calculating both K1 and Vd values. If the K1 value in the two-compartment model can be assumed to be constant, the radioactivity of one SPECT scan at 180 min after injection can be considered to tabulate as a function of Vd for a given K1 value and a given input function, and a table look-up procedure provides the corresponding Vd value. The purpose of this study was to develop a simple, autoradiographic method for quantification of BP by using one SPECT scan and calibrated standard input function with one blood sampling. SPECT studies were performed on 14 patients. A dynamic SPECT scan was initiated following an intravenous bolus injection of Iomazenil. A static SPECT scan was performed at 180 min after the injection. Frequent blood sampling from the brachial artery was performed on all subjects to determine the arterial input function. Simulation studies revealed that errors in calculated Vd values were around +/-10-15% for varied K1 values. A good correlation was observed between total distribution volume values calculated by three-compartment model analysis and those calculated by the present method (r = 0.90), supporting the validity of this method. The present method is simple and applicable for clinical use, and will be able to provide images of BP.


A Method for Reducing Secondary Field Effects in Asymmetric MRI Gradient Coil Design.
This research introduces an original method for the design of MRI gradient coils that reduces secondary field effects created by eddy current coupling. The method is able to deal with asymmetric coils and provides a new way to ensure a reduction in the magnitude of the eddy current induced fields. New constraints are introduced at the surface of passive objects to bind the normal field component below a given value. This value is determined by first treating the passive surface as an active surface, and then, calculating the ideal stream function on that surface to produce the desired secondary field. Two coils were designed, one to image the knee and the other to image the head and neck. The secondary field was analyzed using linear regression and was found to improve the secondary field from 10.41 to 0.498 mT/m and from 7.84 to 0.286 mT/m in the examples used. The power loss in the passive structure also decreased to below 1% of the original value using the new method. The method shows the ability to constrain the field to values below the minimum seen under the traditional approaches. This will allow the design of asymmetric systems with highly linear, reduced magnitude of secondary fields and may lead to better image quality.


Biochemical biomarker responses to pollution in selected sentinel organisms across the Eastern Mediterranean and the Black Sea.
Pollution effects were assessed by means of biochemical biomarkers (catalase, glutathione S-transferase and acetylcholinesterase activities, and metallothioneins content) in five species at selected coastal sites across the Eastern Mediterranean and the Black Sea. The mussel Mytilus galloprovincialis, a well-established sentinel species, was investigated in the Adriatic Sea, Aegean Sea, and Black Sea. The mussel Brachidontes pharaonis and the striped red mullet Mullus surmuletus were used in the Levantine Sea where M. galloprovincialis is not present. The white seabream Diplodus sargus sargus and the gastropod Rapana venosa were additionally sampled in the Adriatic and the Black Sea, respectively. Mussels showed catalase, glutathione S-transferase, and acetylcholinesterase responses to pollution in most geographical areas while the response of metallothioneins was restricted to a few sites. R. venosa showed marked responses of catalase and metallothioneins whereas both fish species did not generally exhibit variations in biomarker values among sites. The approach based on the reference deviation concept using the "Integrated Biological Responses version 2" index was useful for the interpretation of overall biomarker responses.


The Role of Glucagon in Glycemic Variability in Type 1 Diabetes: A Narrative Review.
Type 1 diabetes mellitus (T1DM) is a progressive disease as a result of the severe destruction of islet β-cell function, which leads to high glucose variability in patients. However, α-cell function is also compromised in patients with T1DM, characterized by aberrant fasting and postprandial glucagon secretion. According to recent studies, this aberrant glucagon secretion plays an increasing role in hyperglycemia, insulin-induced hypoglycemia and exercise-associated hypoglycemia in patients with T1DM. With application of continuous glucose monitoring system, dozens of metrics enable the assessment of glycemic variability, which is an integral component of glycemic control for patients with T1DM. There is growing evidences to illustrate the contribution of glucagon secretion to the glycemic variability in patients with T1DM, which may promote the development of new treatment strategies aiming to mitigate glycemic variability associated with aberrant glucagon secretion.


Concentrations of polycyclic aromatic hydrocarbons in Vietnamese takeaway coffee: effects of coffee variety, roasting temperature and time.
The research goal was to estimate the level of risk to human health posed by polycyclic aromatic hydrocarbons (PAHs) in Vietnamese takeaway coffee. A variety of roasted coffee beans were collected and tested for the presence of PAHs in various takeaway locations throughout Vietnam. Furthermore, the effect of roasting conditions on PAH concentrations in Vietnamese Robusta coffee was also studied and demonstrated. Gas chromatography-mass spectrometry, a modern, accurate, and fast method, was used to determine the research results. Six PAHs, namely naphthalene, anthracene, pyrene, fluorene, phenanthrene, and benz[a]anthracene, were found in the 100 collected samples, with average concentrations (μg/kg dry weight) of 943.7 ± 40.3, 195.1 ± 4.9, 36.1 ± 1.1, 33.3 ± 2.2, 28.2 ± 1.7, and 2.0 ± 0.1, respectively. It was found that the tested samples were almost free of PAH4 contamination. The research showed that the total value of PAH quantifications in Robusta coffee increased with increasing roasting temperature and decreased with increasing roasting time. In addition, the calculated value of the total hazard quotient (THQ) was less than 1, and the obtained value of the incremental lifetime carcinogenic risk (ILCR) did not exceed 1·10-5, meaning that coffee consumers in Vietnam are safe from exposure to PAHs present in the investigated coffee beans.


Mortality in hospitalised older patients: the WHALES short-term predictive score.
To develop and validate the WHALES screening tool predicting short-term mortality (3 months) in older patients hospitalised in an acute geriatric unit. Older patients transferred to an acute geriatric ward from June 2017 to December 2018 were included. The cohort was divided into two groups: derivation (n=664) and validation (n=332) cohorts. Cause for admission in emergency room, hospitalisation history within the previous year, ongoing medical conditions, cognitive impairment, frailty status, living conditions, presence of proteinuria on a urine strip or urine albumin-to-creatinine ratio and abnormalities on an ECG were collected at baseline. Multiple logistic regressions were performed to identify independent variables associated with mortality at 3 months in the derivation cohort. The prediction score was then validated in the validation cohort. Five independent variables available from medical history and clinical data were strongly predictive of short-term mortality in older adults including age, sex, living in a nursing home, unintentional weight loss and self-reported exhaustion. The screening tool was discriminative (C-statistic=0.74 (95% CI: 0.67 to 0.82)) and had a good fit (Hosmer-Lemeshow goodness-of-fit test (X2 (3)=0.55, p=0.908)). The area under the curve value for the final model was 0.74 (95% CI: 0.67 to 0.82). The WHALES screening tool is a short and rapid tool predicting 3-month mortality among hospitalised older patients. Early identification of end of life may help appropriate timing and implementation of palliative care.


Mammography utilization among Turkish women.
In Turkey, breast cancer is the leading type of cancer and cause of cancer-related deaths among women, but information is limited on mammography practices. The objectives of the present study were to identify associations between attitudes and knowledge about mammography and socio-demographic indicators and having a mammogram. The participants of this cross-sectional and descriptive study were 1,208 women who attended the primary health care unit serving as a training unit of the medical faculty or the outpatient clinic for breast diseases of the same medical faculty's hospital between October and December 2007. A printed questionnaire covering socio-demographic variables, family history of breast cancer, mammography practices, and attitudes and knowledge of mammography was filled out in face-to-face interviews with the authors. Women with previously diagnosed breast cancer were excluded from the study. We performed chi square and logistic regression analyses. We found that 12.7% of the women had no knowledge of mammography, and 57.3 % had never had a mammogram. Fifty point six percent of our study group reported that they had had a clinical breast examination at least once, and 51.1% were aware of breast self examination (BSE). Need factors such as age and health-system-related factors such as awareness of BSE and having CBE were found to be more important than the socio-economic factors in mammography use. Mammography was accepted by 92.3% as a useful screening method for early detection of breast cancer and as a necessity for women of 50 years and over by the 90.6% of the study group. We found a positive attitude towards mammography and its importance but limited usage.


Bioinspired Squid Peptides─A Tale of Curiosity-Driven Research Leading to Unforeseen Biomedical Applications.
ConspectusThe molecular design of many peptide-based materials originates from structural proteins identified in living organisms. Prominent examples that have garnered broad interdisciplinary research interest (chemistry, materials science, bioengineering, etc.) include elastin, silk, or mussel adhesive proteins. The critical first steps in this type of research are to identify a convenient model system of interest followed by sequencing the prevailing proteins from which these biological structures are assembled. In our laboratory, the main model systems for many years have been the hard biotools of cephalopods, particularly their parrot-like tough beak and their sucker ring teeth (SRT) embedded within the sucker cuptions that line the interior surfaces of their arms and tentacles. Unlike the majority of biological hard tissues, these structures are devoid of biominerals and consist of protein/polysaccharide biomolecular composites (the beak) or, in the case of SRT, are entirely made of proteins that are assembled by supramolecular interactions.In this Account, we chronicle our journey into the discovery of these intriguing biological materials. We initially focus on their excellent mechanical robustness followed by the identification and sequencing of the structural proteins from which they are built, using the latest "omics" techniques including next-generation sequencing and high-throughput proteomics. A common feature of these proteins is their modular architecture at the molecular level consisting of short peptide repeats. We describe the molecular design of these peptide building blocks, highlighting the consensus motifs identified to play a key role in biofabrication and in regulating the mechanical properties of the macroscopic biological material. Structure/property relationships unveiled through advanced spectroscopic and scattering techniques, including Raman, infrared, circular dichroism, and NMR spectroscopies as well as wide-angle and small-angle X-ray scattering, are also discussed.We then present recent developments in exploiting the discovered molecular designs to engineer peptides and their conjugates for promising biomedical applications. One example includes short peptide hydrogels that self-assemble entirely under aqueous conditions and simultaneously encapsulate large macromolecules during the gelation process. A second example involves peptide coacervate microdroplets produced by liquid-liquid phase separation. These microdroplets are capable of recruiting and delivering large macromolecular therapeutics (genes, mRNA, proteins, peptides, CRISPR/Cas 9 modalities, etc.) into mammalian cells, which introduces exciting prospects in cancer, gene, and immune therapies.This Account also serves as a testament to how curiosity-driven explorations, which may lack an obvious practical goal initially, can lead to discoveries with unexpected and promising translational potential.


Handwriting: three-dimensional kinetic synergies in circle drawing movements.
The purpose of this study was to investigate central nervous system (CNS) strategies for controlling multifinger forces during a circle-drawing task. Subjects drew 30 concentric, discontinuous clockwise and counter clockwise circles, at self and experimenter-set paces. The three-dimensional trajectory of the pen's center of mass and the three-dimensional forces and moments of force at each contact between the hand and the pen were recorded. Uncontrolled Manifold Analysis was used to quantify the synergies between pen-hand contact forces in radial, tangential and vertical directions. Results showed that synergies in the radial and tangential components were significantly stronger than in the vertical component. Synergies in the clockwise direction were significantly stronger than the counterclockwise direction in the radial and vertical components. Pace was found to be insignificant under any condition.


Drivers of Variability in 90-Day Cost for Elective Anterior Cervical Discectomy and Fusion for Cervical Degenerative Disease.
Value-based episode of care reimbursement models is being investigated to curb unsustainable health care costs. Any variation in the cost of index spine surgery can affect the payment bundling during the 90-d global period. To determine the drivers of variability in cost for patients undergoing elective anterior cervical discectomy and fusion (ACDF) for degenerative cervical spine disease. Four hundred forty-five patients undergoing elective ACDF for cervical spine degenerative diagnoses were included in the study. The direct 90-d cost was derived as sum of cost of surgery, cost associated with postdischarge utilization. Multiple variable linear regression models were built for total 90-d cost. The mean 90-d direct cost was $17685 ± $5731. In a multiple variable linear regression model, the length of surgery, number of levels involved, length of hospital stay, preoperative history of anticoagulation medication, health-care resource utilization including number of imaging, any complications and readmission encounter were the significant contributor to the 90-d cost. The model performance as measured by R2 was 0.616. There was considerable variation in total 90-d cost for elective ACDF surgery. Our model can explain about 62% of these variations in 90-d cost. The episode of care reimbursement models needs to take into account these variations and be inclusive of the factors that drive the variation in cost to develop a sustainable payment model. The generalized applicability should take in to account the differences in patient population, surgeons' and institution-specific differences.


Host immune response to Plasmodium.
Malaria is the most widely spread infectious disease of man affecting almost half of the world's population. Control of malaria remains one of the world's biggest health challenges. Development of vaccines has been considered a valid and necessary complement to control malaria in addition to the control measures of the vectors. The Plasmodium parasites that cause the disease have many stages in their cycle, each with distinct morphology and antigenicity. Understanding the activation, interaction and effector function of the different components of the immune system in relation to target antigens on different stages of malaria parasites is necessary to achieve complete protection by vaccination.


Intrathecal Drug Delivery (ITDD) systems for cancer pain.
Intrathecal drug delivery is an effective pain management option for patients with chronic and cancer pain. The delivery of drugs into the intrathecal space provides superior analgesia with smaller doses of analgesics to minimize side effects while significantly improving quality of life. This article aims to provide a general overview of the use of intrathecal drug delivery to manage pain, dosing recommendations, potential risks and complications, and growing trends in the field.


Medical comorbidities predict mortality in women with a history of early stage breast cancer.
This analysis was conducted to determine whether comorbid medical conditions predict additional breast cancer events and all-cause mortality in women with a history of early stage breast cancer. Women (n = 2,542) participating in a randomized diet trial completed a self-administered questionnaire regarding whether they were currently being treated for a wide variety of diseases (cardiovascular, diabetes, gallbladder, gastrointestinal, arthritis, and osteoporosis) and conditions (high blood pressure, elevated cholesterol level). Height and weight were measured at baseline. Participants were followed for a median of 7.3 years (range 0.8-15.0). Cox regression analysis was performed to assess whether comorbidities predicted disease-free and overall survival; hazard ratio (HR) was the measure of association. Overall, there were 406 additional breast cancer events and 242 deaths. Participants with diabetes had over twofold the risk of additional breast cancer events (HR 2.1, 95% CI: 1.3, 3.4) and mortality (HR 2.5, 95% CI: 1.4, 4.4). The presence of multiple comorbidities did not statistically significantly predict additional breast cancer events. However, compared to no comorbidities, participants with 3 or more comorbidities had a HR of 2.1, 95% CI: 1.3, 3.3 for mortality. In conclusion, type 2 diabetes is associated with poor breast cancer prognosis. Given that 85% of deaths were caused by breast cancer, these findings suggest that multiple comorbidities may reduce the likelihood of surviving additional breast cancer events.


Barrett's Epithelial Thickness, Assessed by Volumetric Laser Endomicroscopy, Is Associated With Response to Radiofrequency Ablation.
Radiofrequency ablation (RFA) is the most common treatment for flat Barrett's esophagus (BE), but reasons for varying outcomes are poorly understood. A recently developed contrast-enhancement algorithm allows reliable measurement of Barrett's epithelial thickness (BET) from volumetric laser endomicroscopy (VLE) images and correlation with response to RFA. Using this algorithm, we investigated whether patients with thicker Barrett's mucosa are less likely to respond to RFA. In the future, this algorithm may guide choice of RFA dosing or endoscopic resection. We performed a retrospective analysis on all patients with BE who received a baseline VLE scan between May 2015 and October 2016, followed by RFA and 1 follow-up exam, from 14 institutions participating in the United States VLE registry. We measured BET on equidistant locations by estimating the distance between the esophageal surface and the superficial edge of the deepest lamina propria. The primary outcome variable was the percentage reduction in Prague length; secondary outcome variables were complete remission of intestinal metaplasia (CRIM) and presence of strictures after 12 months. Images from 61 patients were included in our final analysis. Mean BET per patient ranged from 224 μm to 705 μm. A 100 μm thicker mean BET per patient resulted in a 12% lower response to treatment, measured by a reduction of Prague length (P = .03), after adjustment for confounders. We found an association between mean BET and CRIM, but not with stricture formation. Based on measurements on contrast-enhanced VLE images, we found that BET correlates with response to RFA. For clinical implementation, larger studies with a standardized follow-up and development of computer-aided image analysis systems are needed.


Molecular control of the induction of alcohol dehydrogenase by ethanol in Drosophila melanogaster larvae.
The activity of alcohol dehydrogenase (ADH:EC 18.104.22.168), the initial enzyme in the major pathway for ethanol degradation, is induced in Drosophila melanogaster larvae by low concentrations of dietary ethanol. Two lines of evidence indicate that the metabolic products of the ADH pathway for ethanol degradation are not directly involved in the induction of Adh. First, the accumulation of the proximal transcript in Adhn2 larvae was increased when the intracellular level of ethanol was elevated. In addition, the ADH activity, the proximal Adh mRNA, and the intracellular concentration of ethanol were elevated coordinately in wild-type larvae fed hexadeuterated-ethanol, which is metabolized more slowly than normal ethanol. An examination of P element transformant lines with specific deletions in the 5' regulatory DNA of the Adh gene showed that a DNA sequence between +527 and +604 of the distal transcript start site is essential for the induction of the Adh gene [corrected]. The DNA sequence between -660 and about -5000 of the distal transcript start site was important for the down-regulation of the induction response.


Nuclear localization of bacterial Streptoalloteichus hindustanus bleomycin resistance protein in mammalian cells.
Prokaryotes produce a variety of toxins that affect genomic function of both eukaryotes and prokaryotes. The 375-base pair bacterial gene Streptoalloteichus hindustanus (Sh) ble encodes a small protein, Streptoalloteichus hindustanus bleomycin resistance protein (BRP), that inhibits in vitro DNA cleavage by the prokaryotic glycopeptide bleomycin, which is a clinically used anticancer drug. NIH/3T3 cells infected with a retroviral vector containing Sh ble (SH-9 cells) were highly resistant to the cytotoxicity of bleomycin-like drugs but not to the cytotoxicity of other, structurally unrelated, DNA-cleaving agents. Expression of BRP did not markedly alter total cellular content or distribution of bleomycin-like compounds. Fluorescently labeled bleomycin was primarily localized in cytoplasmic vesicles in NIH/3T3 and SH-9 cells, whereas BRP, which has no established nuclear localization sequence, was segregated to the nucleus and more specifically to euchromatin. This karyophilic BRP may intercept bleomycin in the nucleus.


Angiotensin-converting enzyme inhibitors, inhibition of brain and peripheral angiotensin-converting enzymes, and left ventricular dysfunction in rats after myocardial infarction.
The brain renin-angiotensin system contributes significantly to progressive left ventricular (LV) dysfunction in rats after myocardial infarction (MI). The present study evaluated the effects of central versus peripheral plus central angiotensin-converting enzyme (ACE) blockade on sympathetic activity, and LV anatomy and function after MI. Wistar rats were treated for 4 weeks after MI with the lipophilic ACE inhibitor trandolapril at 5 mg/kg/day or the hydrophilic blocker lisinopril at 50 mg/kg/day by once daily subcutaneous injection, or with a central infusion of lisinopril at 0.1 mg/kg/day. At 24 hours after the last dose, subcutaneous trandolapril caused 70% to 80% ACE inhibition in both brain and kidneys; lisinopril caused 10% to 20% less. Central infusion of lisinopril caused 70% inhibition of brain ACE and minimal (6%) inhibition in the kidneys. All three treatments similarly improved sympathetic reactivity and arterial baroreflex function. All three treatments lowered cardiac Ang I and II, and similarly attenuated the increases in LV end diastolic pressure, circumference, and fibrosis. Both subcutaneous treatments further decreased LV peak systolic pressure and dP/dt max, whereas icv lisinopril caused no change. Despite marked differences in the extent of peripheral blockade, all three treatments similarly affected sympathetic activity and decreased cardiac Ang II, preload and remodeling after MI. One may speculate that central and peripheral ACE-mediated mechanisms are sequential and therefore only minor additional effects of peripheral ACE blockade are noted.


The effects of plyometric exercise on unilateral balance performance.
The purpose of this study was to determine the effects of plyometric exercise on unilateral balance performance. Nine healthy adults performed baseline measurements on the dominant limb that consisted of: a 20-s unilateral stability test on a tilt balance board, where a higher stability index represented deterioration in balance performance; isokinetic plantar flexion torque at 0.52 and 3.14 rad s(-1); muscle soreness in the calf region; and resting plantar flexion angle. Plyometric exercise consisted of 200 counter-movement jumps designed to elicit symptoms of muscle damage, after which baseline measurements were repeated at 30 min, 24, 48, and 72 h. Perceived muscle soreness of the calf region increased significantly following the plyometric exercise protocol (F(4,32) = 17.24, P < 0.01). Peak torque was significantly reduced after the plyometric exercise protocol (F(4,32) = 7.49, P < 0.05), with greater loss of force at the lower angular velocity (F(4,32) = 3.46, P < 0.05), while resting plantar flexion angle was not significantly altered compared with baseline values (P > 0.05). The stability index was significantly increased (F(4,32) = 3.10, P < 0.05) above baseline (mean 2.3, s = 0.3) at 24 h (3.3, s = 0.4), after which values recovered. These results indicate that there is a latent impairment of balance performance following a bout of plyometric exercise, which has implications for both the use of skill-based activities and for increased injury risk following high-intensity plyometric training.


Interpretation of volumetric laser endomicroscopy in Barrett's esophagus using image enhancement software.
Image interpretation of Barrett's esophagus (BE) with volumetric laser endomicroscopy (VLE) can be enhanced by image processing software that highlights established features using a color-graded scale (intelligent real-time image segmentation, IRIS). This study aims to provide a description of IRIS features of various gastroesophageal tissue types using histologic correlation. A database of 80 VLE laser-marked targets with histologic correlation was reviewed for various tissue types. IRIS was applied off-line to the VLE scans, laser-marked targets were identified, and feature review was performed. Squamous epithelium targets (N = 7) showed IRIS layered architecture with lack of surface hyper-reflectivity and epithelial glands. Gastric cardia targets (N = 10) showed absent layering (100%) and surface hyper-reflectivity with epithelial glands (40%). Nondysplastic BE targets (N = 39) showed surface hyper-reflectivity (64%), epithelial glands (51%), and lack of layering (74%). Targets of BE with early neoplasia (N = 24), showed surface hyper-reflectivity (96%), epithelial glands (67%), and lack of layering (96%). IRIS features that characterize each tissue type appear to mirror the nonenhanced VLE counterparts that define them.


Globus hystericus or depressivus?
Globus hystericus has been often classified as a conversion disorder. More than half of the sufferers are overtly depressed and only a handful have hysterical personality. It is argued that it might be more appropriately viewed as a psychophysiological symptom of depression that responds to antidepressant treatment.


[Multivariate analysis of relationship between breast feeding and infant physical development].
Longitudinal analysis with generalized estimating equation (GEE) revealed breast feeding can promote infant physical development and growth, and cross-sectional analysis with canonical correlation showed protein intake with breast milk as its main source brought about infants to develop physically tall and lean at first, which might support the theory that protein intake affects more on their development and growth. The extent of infant physical development and growth varied with the amount of breast milk of his or her mother, which should be caught attention in comparison of infant physical development with different feeding patterns. It is suggested that intervention of breast feeding should be implemented during perinatal period and 1-2 months after delivery with emphasis on health education.


COVID-19-Associated Pulmonary Aspergillosis: A Single-Center Experience in Central Valley, California, January 2020-March 2021.
Reports of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) have been widely published across the world since the onset of the pandemic with varying incidence rates. We retrospectively studied all patients with severe COVID-19 infection who were admitted to our tertiary care center's intensive care units between January 2020 and March 2021, who also had respiratory cultures positive for Aspergillus species. Among a large cohort of 970 patients admitted to the ICU with severe COVID-19 infections during our study period, 48 patients had Aspergillus species growing in respiratory cultures. Based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus criteria, 2 patients in the study had proven CAPA, 9 had probable CAPA, and 37 had possible CAPA. The incidence of CAPA was 5%. The mean duration from a positive COVID-19 test to Aspergillus spp. being recovered from the respiratory cultures was 16 days, and more than half of the patients had preceding fever or worsening respiratory failure despite adequate support and management. Antifungals were given for treatment in 44% of the patients for a mean duration of 13 days. The overall mortality rate in our study population was extremely high with death occurring in 40/48 patients (83%).


A systematic review and meta-analysis of hyperbaric oxygen therapy for diabetic foot ulcers with arterial insufficiency.
Diabetic foot ulcers (DFUs) are frequently associated with peripheral arterial occlusive disease (PAOD) and may ultimately lead to amputations of the lower extremity. Adjuvant hyperbaric oxygen treatment (HBOT) might foster better wound healing and lower amputation rates in patients with DFU and PAOD. A systematic review was conducted to assess the effects of HBOT as an adjunctive therapy to standard treatment for patients with DFUs with PAOD. Systematic review using the MEDLINE, EMBASE, and Cochrane CENTRAL databases (from inception to October 2018). All original, comparative studies on the effect of HBOT on DFUs with PAOD were eligible. The primary outcome measures were amputation rate, amputation-free survival, complete ulcer healing, and mortality. Eleven studies, totaling 729 patients, were included for analysis, including 7 randomized clinical trials, 2 controlled clinical trials, and 2 retrospective cohorts. Four were used for quantitative synthesis. Meta-analysis showed a significantly fewer major amputations in the HBOT group (10.7% vs 26.0%; risk difference, -15%; 95% confidence interval [CI], -25 to -6; P = .002; number needed to treat, 7; 95% CI, 4-20). No difference was found for minor amputations (risk difference, 8%; 95% CI, -13 to 30; P = .46). Three studies reporting on complete wound healing showed contrasting results. No significant difference was found for mortality or amputation-free survival. Current evidence shows that adjuvant HBOT improves major amputation rate, but not wound healing, in patients with DFUs and PAOD. Given the wide range of patients included in the trials, better patient selection may help define which patients with DFUs and PAOD benefit most from HBOT as standard adjunctive treatment.


UAE population reference standard charts for body mass index and skinfold thickness, at ages 0-18 years.
To determine a range of anthropometric measurements including skinfold thickness measurements in four different areas of the body, to construct population growth charts for body mass index (BMI), skinfolds, and to compare these with growth charts from other countries. One aim was also to validate body fat charts derived from skinfold thickness. A national cross-sectional growth survey of children, 0-18 years old, was conducted using multistage stratified random sampling. The sample size included at least 200 children in each age-sex group. Height, weight, biceps skinfold, triceps skinfold, subscapular skinfold, suprailiac skinfold, and mid-upper-arm circumference were measured in each child. We describe correlation, standard deviation scores relative to the other standards, and calculation of body density in the United Arab Emirates population. We determined whether any of the above is a good indicator of fatness in children. BMI, upper-arm circumference, sum of four skinfolds, and percentage body fat charts were constructed using the LMS method of smoothing. BMI was very significantly correlated with sum of skinfold thicknesses, and mid-upper-arm circumference. Prevalence of obesity and overweight in ages 13-17 years was respectively 9.94% and 15.16% in females and 6.08% and 14.16% in males. Derived body fat charts were found not to be accurate. A national BMI, upper-arm circumference, and sum of four skinfolds chart has been constructed that can be used as a reference standard for the United Arab Emirates. Sum of four skinfold thickness charts can be used as crude determinants of adiposity in children, but derived body fat charts were shown to be inaccurate.


Soft Poly(N-vinylcaprolactam) Based Aqueous Particles.
Soft nanoparticles are an important class of material with potential to be used as carriers of active compounds. Swollen, penetrable particles can act as a host for the active ingredients and provide stability, stimuli-responsiveness and recyclability for the guest. Thermoresponsive colloidal gel particles are especially attractive for such applications due to the extremely soft structure, size and responsiveness. Poly(N-vinylcaprolactam) (PNVCL) is a much studied, popular thermoresponsive polymer. The polymer has low toxicity and the phase transition temperature is close to body temperature. During the phase transition, the polymer becomes less soluble, the particle expels a large part of water and the particle collapses to a more compact form. The diffusion of material in and from the particles is largely affected by this transition. As the solubility of the polymer changes, so do the interactions with the loaded compound. This feature article focuses on the synthetic methods, properties and applications of soft PNVCL particles.


An analysis of prognostic factors in early stage Hodgkin's disease.
An analysis of prognostic factors has been carried out in 398 patients presenting with clinical Stage I and II Hodgkin's disease treated between 1963 and 1979. By life table analysis older age, lymphocyte depletion histology, systemic symptoms, mediastinal node bulk, and erythrocyte sedimentation rate (ESR) greater than 40 mm/h were associated with a significantly worse survival probability. On multiple factor regression analysis only age and stage were independent prognostic variables for survival, with systemic symptoms having borderline significance. Using this information, together with other analyses of prognosis in early Hodgkin's disease three groups of patients are defined. The first with a predicted 5-year survival of 78% would include patients possessing at least one of the following features; age greater than 60, lymphocyte depletion, greater than 3 sites involved, systemic symptoms, mediastinal/thoracic ratio of greater than 1/3. The second groups present with at least two of the following factors; ESR greater than 40 mm/h, male sex, 3 involved sites, or mixed cellularity histology, and the 5 year survival probability is 84%. The remaining Stage I and II patients would constitute a good prognosis group with a predicted 5-year survival of 92%.


Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells.
Bacillus anthracis secretes two critical virulence factors, lethal toxin (LT) and edema toxin (ET). In this study, we show that murine bone marrow-derived dendritic cells (DC) infected with B. anthracis strains secreting ET exhibit a very different cytokine secretion pattern than DC infected with B. anthracis strains secreting LT, both toxins, or a nontoxinogenic strain. ET produced during infection selectively inhibits the production of IL-12p70 and TNF-alpha, whereas LT targets IL-10 and TNF-alpha production. To confirm the direct role of the toxins, we show that purified ET and LT similarly disrupt cytokine secretion by DC infected with a nontoxinogenic strain. These effects can be reversed by specific inhibitors of each toxin. Furthermore, ET inhibits in vivo IL-12p70 and IFN-gamma secretion induced by LPS. These results suggest that ET produced during infection impairs DC functions and cooperates with LT to suppress the innate immune response. This may represent a new strategy developed by B. anthracis to escape the host immune response.


Luminescent platinum(II) complexes with functionalized N-heterocyclic carbene or diphosphine selectively probe mismatched and abasic DNA.
The selective targeting of mismatched DNA overexpressed in cancer cells is an appealing strategy in designing cancer diagnosis and therapy protocols. Few luminescent probes that specifically detect intracellular mismatched DNA have been reported. Here we used Pt(II) complexes with luminescence sensitive to subtle changes in the local environment and report several Pt(II) complexes that selectively bind to and identify DNA mismatches. We evaluated the complexes' DNA-binding characteristics by ultraviolet/visible absorption titration, isothermal titration calorimetry, nuclear magnetic resonance and quantum mechanics/molecular mechanics calculations. These Pt(II) complexes show up to 15-fold higher emission intensities upon binding to mismatched DNA over matched DNA and can be utilized for both detecting DNA abasic sites and identifying cancer cells and human tissue samples with different levels of mismatch repair. Our work highlights the potential of luminescent Pt(II) complexes to differentiate between normal cells and cancer cells which generally possess more aberrant DNA structures.


Nanoparticle adsorption dynamics at fluid interfaces.
Understanding the dynamic adsorption of nanoparticles (NPs) at fluid interfaces is important for stabilizing emulsions and for the preparation of 2D NP-based materials. Here we show that the Ward-Tordai equations commonly employed to describe the dynamics of surfactant adsorption at a fluid interface combined with a Frumkin adsorption isotherm can be employed to model the diffusion-limited adsorption of NPs onto a fluid interface. In contrast to surfactants, an additional wetting equation of state (EOS) must be incorporated to characterize the dynamic interfacial tension during the adsorption of NPs to the oil-water interface. Our results show agreement between the model and experiments with NP area fractions <0.3. Slower dynamics are observed at larger area fractions, which are speculated to arise from polydispersity or re-organization at the interface. We show the model can be extended to the competitive adsorption between the NPs and a surface active species.


Intra-individual methylomics detects the impact of early-life adversity.
Genetic and environmental factors interact during sensitive periods early in life to influence mental health and disease via epigenetic processes such as DNA methylation. However, it is not known if DNA methylation changes outside the brain provide an "epigenetic signature" of early-life experiences. Here, we used a novel intra-individual approach by testing DNA methylation from buccal cells of individual rats before and immediately after exposure to one week of typical or adverse life experience. We find that whereas inter-individual changes in DNA methylation reflect the effect of age, DNA methylation changes within paired DNA samples from the same individual reflect the impact of diverse neonatal experiences. Genes coding for critical cellular metabolic enzymes, ion channels, and receptors were more methylated in pups exposed to the adverse environment, predictive of their repression. In contrast, the adverse experience was associated with less methylation on genes involved in pathways of death and inflammation as well as cell-fate-related transcription factors, indicating their potential up-regulation. Thus, intra-individual methylome signatures indicate large-scale transcription-driven alterations of cellular fate, growth, and function.


Pentoxifylline in the treatment of refractory nephrotic syndrome secondary to lupus nephritis.
To evaluate the efficacy of pentoxifylline in the treatment of refractory nephrotic syndrome secondary to lupus nephritis. We studied 11 patients who met the following inclusion criteria: (1) systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria; (2) lupus nephritis class III, IV, or V according to the World Health Organization; (3) proteinuria in the nephrotic range (> or = 3 g/24 h) for at least 6 months despite treatment. All patients received pentoxifylline 800-1600 mg/day. Clinical and laboratory data, including creatinine, urine test, creatinine clearance, and 24-h urinary protein, were collected monthly for 6 months. No changes in treatment were allowed, except for alterations in the dose of prednisone. All patients had received corticosteroids and immunosuppressants for at least 6 months. All patients showed a decrease in proteinuria concentrations after use of pentoxifylline from a median of 5.5 to 2.0 (p = 0.003). No patient discontinued the drug due to side effects. One patient had nausea and one had anxiety that disappeared after decreasing the dosage. Pentoxifylline seems to be effective in the treatment of refractory nephrotic syndrome secondary to lupus nephritis.


Effects of acepromazine on the stress response in Southern chamois (Rupicapra pyrenaica) captured by means of drive-nets.
This study was conducted to assess the stress response of Southern chamois (Rupicapra pyrenaica) to capture and physical restraint and the effects of acepromazine (a short-acting neuroleptic) on this response. Forty free-ranging Southern chamois were captured, injected intramuscularly with acepromazine (19 animals, randomly selected) or saline (the other 21 animals), and physically restrained for 3 h. Heart rate and body temperature were monitored with telemetric devices, and blood samples were obtained at capture and every hour thereafter to determine hematologic and serum biochemical parameters. The lower heart-rate variability, temperature, erythrocyte count, hemoglobin concentration, packed cell volume (PCV), and serum creatine kinase activity in the animals treated with acepromazine indicated that this agent reduced the adverse effects of stress. According to the differences in heart rate, erythrocyte count, hemoglobin concentration, PCV, lymphocyte count, and serum concentrations of glucose, creatinine, chloride, and potassium, alpha-adrenergic stimulation by catecholamines seemed to be stronger in females, whereas the adrenal-cortex reaction seemed to be stronger in males. The differences in erythrocyte parameters, temperature, serum creatine kinase activity, and serum concentrations of potassium and chloride indicated that acepromazine's beneficial effects were greater in females.


Transduced Tat-alpha-synuclein protects against oxidative stress in vitro and in vivo.
Parkinson's disease (PD) is a common neurodegenerative disorder and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although many studies showed that the aggregation of alpha-synuclein might be involved in the pathogenesis of PD, its protective properties against oxidative stress remain to be elucidated. In this study, human wild type and mutant alpha-synuclein genes were fused with a gene fragment encoding the nine amino acid transactivator of transcription (Tat) protein transduction domain of HIV-1 in a bacterial expression vector to produce a genetic in-frame WT Tat-alpha-synuclein (wild type) and mutant Tat-alpha-synucleins (mutants; A30P and A53T), respectively, and we investigated the protective effects of wild type and mutant Tat-alpha-synucleins in vitro and in vivo. WT Tat-alpha-synuclein rapidly transduced into an astrocyte cells and protected the cells against paraquat induced cell death. However, mutant Tat-alpha-synucleins did not protect at all. In the mice models exposed to the herbicide paraquat, the WT Tat-alpha-synuclein completely protected against dopaminergic neuronal cell death, whereas mutants failed in protecting against oxidative stress. We found that these protective effects were characterized by increasing the expression level of heat shock protein 70 (HSP70) in the neuronal cells and this expression level was dependent on the concentration of transduced WT Tat-alpha-synuclein. These results suggest that transduced Tat-alpha-synuclein might protect cell death from oxidative stress by increasing the expression level of HSP70 in vitro and in vivo and this may be of potential therapeutic benefit in the pathogenesis of PD.


Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes.
The crystal structure of human alpha class glutathione transferase A1-1 has been determined and refined to a resolution of 2.6 A. There are two copies of the dimeric enzyme in the asymmetric unit. Each monomer is built from two domains. A bound inhibitor, S-benzyl-glutathione, is primarily associated with one of these domains via a network of hydrogen bonds and salt-links. In particular, the sulphur atom of the inhibitor forms a hydrogen bond to the hydroxyl group of Tyr9 and the guanido group of Arg15. The benzyl group of the inhibitor is completely buried in a hydrophobic pocket. The structure shows an overall similarity to the mu and pi class enzymes particularly in the glutathione-binding domain". The main difference concerns the extended C terminus of the alpha class enzyme which forms an extra alpha-helix that blocks one entrance to the active site and makes up part of the substrate binding site.


Prevention, Monitoring, and Management of Cardiac Dysfunction in Patients with Metastatic Breast Cancer.
Cardiac monitoring is becoming an important part of breast cancer care. Breast cancer and cardiovascular disease (CVD) share many common risk factors, and it is estimated that by the median age of diagnosis, many patients with breast cancer will have established or subclinical CVD. In addition, a number of treatments for metastatic breast cancer are known to have cardiac effects. As such, there is a clear need to prevent, identify, and effectively manage cardiovascular events in patients with breast cancer. Current clinical practice for patients with metastatic breast cancer involves a comprehensive set of assessments to ensure efficacy and safety of treatment. Adding cardiac monitoring to the assessments already required for patients with breast cancer may improve survival and quality of life. Currently, cardiac monitoring is recommended for several breast cancer treatments, and guidelines related to cardiac monitoring are available. Here, we review the risk of CVD in patients with breast cancer, providing an overview of the cardiac events associated with standard therapies for metastatic breast cancer. We also assess the current clinical recommendations relating to cardiac monitoring, and practical management strategies for oncologists. Cardio-oncology is a growing medical subspecialty that promotes the need for effective cancer therapy while minimizing cardiac effects. Integrating cardiac monitoring into routine clinical practice may safeguard patients with metastatic breast cancer against adverse cardiac effects. IMPLICATIONS FOR PRACTICE: This review details the common risk factors associated with cardiovascular disease that are frequently observed in patients with metastatic breast cancer, as well as the adverse cardiac effects of many therapies that are commonly prescribed. The review also provides a rationale for routine and comprehensive cardiovascular assessment of all patients at baseline, and during and after therapy depending on the treatment and presence of risk factors for cardiovascular disease. The medical discipline of cardio-oncology is increasingly being recognized as an important part of clinical practice to ensure effective cancer therapy while maintaining cardiac health.


Pediatric Clinicians' Use of Telemedicine: Qualitative Interview Study.
Bedside manner describes how clinicians relate to patients in person. Telemedicine allows clinicians to connect virtually with patients using digital tools. Effective virtual communication or webside manner may require modifications to traditional bedside manner. This study aims to understand the experiences of telemedicine providers with patient-to-provider virtual visits and communication with families at a single large-volume children's hospital to inform program development and training for future clinicians. A total of 2 focus groups of pediatric clinicians (N=11) performing virtual visits before the COVID-19 pandemic, with a range of experiences and specialties, were engaged to discuss experiential, implementation, and practice-related issues. Focus groups were facilitated using a semistructured guide covering general experience, preparedness, rapport strategies, and suggestions. Sessions were digitally recorded, and the corresponding transcripts were reviewed for data analysis. The transcripts were coded based on the identified main themes and subthemes. On the basis of a higher-level analysis of these codes, the study authors generated a final set of key themes to describe the collected data. Theme consistency was identified across diverse participants, although individual clinician experiences were influenced by their specialties and practices. A total of 3 key themes emerged regarding the development of best practices, barriers to scalability, and establishing patient rapport. Issues and concerns related to privacy were salient across all themes. Clinicians felt that telemedicine required new skills for patient interaction, and not all were comfortable with their training. Telemedicine provides benefits as well as challenges to health care delivery. In interprofessional focus groups, pediatric clinicians emphasized the importance of considering safety and privacy to promote rapport and webside manner when conducting virtual visits. The inclusion of webside manner instructions within training curricula is crucial as telemedicine becomes an established modality for providing health care.


Theoretical convergence guarantees for cooperative coevolutionary algorithms.
Cooperative coevolutionary algorithms have the potential to significantly speed up the search process by dividing the space into parts that can each be conquered separately. However, recent research presented theoretical and empirical arguments that these algorithms tend to converge to suboptimal solutions in the search space, and are thus not fit for optimization tasks. This paper details an extended formal model for cooperative coevolutionary algorithms, and uses it to explore possible reasons these algorithms converge to optimal or suboptimal solutions. We demonstrate that, under specific conditions, this theoretical model will converge to the globally optimal solution. The proofs provide the underlying theoretical foundation for a better application of cooperative coevolutionary algorithms. We demonstrate the practical advantages of applying ideas from this theoretical work to a simple problem domain.


Negative immunoregulatory effects of noradrenaline through alpha2-adrenoceptor activation.
BACKGROUND: There are some reports that catecholamines and beta-adrenoceptor agonists may suppress some immune functions. OBJECTIVES: The present study was carried out in order to examine the effects of noradrenaline (10-5 M, 10-6 M and 10-7 M), yohimbine (10-5 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor antagonist, and clonidine (105 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor agonist, on the stimulated production of interferon-gamma (IFNgamma), a pro-inflammatory cytokine, and interleukin-10 (IL-10), an immuno-inhibitory cytokine. DESIGN: We measured the in vitro production of IFNgamma and IL-10 by stimulated, diluted whole blood of 16 normal volunteers. The IFNgamma/IL-10 production ratio was computed since this ratio reflects the pro- versus anti-inflammatory capacity of the cultured whole blood. RESULTS: We found that 1) noradrenaline, 10-5 M, 10-6 M, and 10-7 M, significantly suppressed the production of IFNgamma and that noradrenaline, 10-5 M, significantly enhanced the production of IL-10. Clonidine, 10-5 M and 10-7 M, significantly suppressed the production of IFNgamma. Noradrenaline, 10-5 M and 10-6 M, and clonidine, 10-5 M, significantly suppressed the IFNgamma/IL-10 production ratio. There were no significant effects of yohimbine on IFNgamma or IL-10 production. CONCLUSIONS: 1) noradrenaline has significant negative immunoregulatory effects in humans through enhancing the production of IL-10 and suppressing that of IFNgamma; and 2) the suppression of the production of IFNgamma is in part related to alpha2-adrenoceptor activation.


How do Adolescents Learn Cyber-victimization Coping Skills? An Examination of Parent and Peer Coping Socialization.
Recently, cyber-victimization has become an ever increasing concern for adolescents. Given the negative consequences of cyber-victimization, it is important to understand how adolescents learn strategies to cope (i.e., "coping socialization") with cyber-victimization. The purpose of this study is to understand common coping strategies reported by adolescents, identify from whom youth learn cyber-victimization coping strategies (coaching), and explore how coaching is associated with adolescents' self-reported use of coping. In a sample of 329 adolescents (49% male; 70% white), we found that positive coping strategies (e.g., problem solving, seeking social support) are used most frequently, and adolescents' perceptions of both parent and peer coping socialization is associated with self-reported use of coping. Interventionists can use this information to adapt interventions to include influential positive socializers.


[Neurophysiological analysis of the central mechanisms of glossalgia].
Bioelectrical activity of the brain was studied in 20 patients with glossalgia characterized by a most severe clinical symptomatology. Neurophysiological analysis has shown a marked imbalance of the leading neuromediator cerebral systems, namely, deficiency of ascending activating reticular effects, tense functioning of syncronizing systems, and involvement into the chain of impaired relationships of the limbic-reticular complex and inhibitory systems of the brain. It has been established that general disorganization of the activity of the cerebral mechanisms is attended by impaired control of ascending afferentation. As a result, any type of chronic stimulation of the peripheral receptors is no longer blocked when entering the central nervous system and manifests in a clinically marked syndrome of glossalgia. On the basis of clinico-physiological correlations the authors draw a conclusion that the syndrome of glossalgia should be considered as one of the links in the chain of chronic emotional stress manifestations.


Psychological morbidity and quality of life of ethnic minority patients with cancer: a systematic review and meta-analysis.
Ethnic minority is associated with higher cancer incidence and poorer survival than is being in the majority group. We did a systematic review and meta-analysis to assess whether psychological morbidity and health-related quality of life (HRQoL) were affected by minority status. We searched Medline, AMED, PsycINFO, Embase, CENTRAL, CINAHL, PubMed, Sociological Abstracts, and Web of Science for English-language articles published between Jan 1, 1995, and October, 2009. Articles were eligible if they reported original data on anxiety, depression, distress (for psychological morbidity), or HRQoL in minority and majority cancer patients or survivors. Minority status was defined as being an immigrant or having an ethnic, linguistic, or religious background different to the majority of the population in the country where the research was done. We excluded African Americans and indigenous groups. Eligible articles were rated for quality of reporting, external validity, internal validity, sample size, and power. Each quality criterion was rated independently by two reviewers until inter-rater reliability was achieved. In a meta-analysis we compared mean scores adjusted for socioeconomic status and other sociodemographic and clinical variables, where available. Effect sizes greater than 0·5 and 95% CI that included 0·5 or -0·5 were deemed clinically important, with negative values indicating worse outcomes in minority patients. We assessed publication bias by estimating the number of potential unpublished studies and the number of non-signficant studies with p=0·05 required to produce a non-significant overall result. We identified 21 eligible articles that included 18 datasets collected in the USA and one in each of Canada, Romania, and the UK. Ethnic minority groups were Hispanic, Asian or Pacific Islander, or Hungarian (one dataset). Overall, we found minority versus majority groups to have significantly worse distress (mean difference -0·37, 95% CI -0·46 to -0·28; p<0·0001), depression (-0·23, -0·36 to -0·11; p=0·0003), and overall HRQoL (-0·33, -0·58 to -0·07; p=0·013). Further analyses found disparities to be specific to Hispanic patients in the USA, in whom poorer outcomes were consistent with potentially clinically important differences for distress (effect size -0·37, 95% CI -0·54 to -0·20; p<0·0001), social HRQoL (-0·45, -0·87 to -0·03; p=0·035), and overall HRQoL (-0·49, -0·78 to -0.20; p=0·0008). Results were significantly heterogeneous for overall HRQoL and all domains. Tests for interaction, for adjusted versus unadjusted and comparisons of high-quality, medium-quality, and low-quality articles, were generally non-significant, which suggests no bias. We found no evidence of any substantive publication bias. Hispanic cancer patients in the USA, but not other ethnic minority groups, report significantly worse distress, depression, social HRQoL, and overall HRQoL than do majority patients, of which all but depression might be clinically important. Heterogeneous results might, however, have limited the interpretation. Data for other minority groups and for anxiety are scarce. More studies are needed from outside the USA. Future reports should more clearly describe their minority group samples and analyses should control for clinical and sociodemographic variables known to predict outcomes. Understanding of why outcomes are poor in US Hispanic patients is needed to inform the targeting of interventions. Prince of Wales Hospital, Sydney, Australia.


Vaginal fluid human chorionic gonadotropin for detection of rupture of membranes.
To evaluate the accuracy of qualitative and quantitative human chorionic gonadotropin (hCG) assays to detect ruptured amniotic membranes (ROM) in term patients. We conducted a prospective cohort study enrolling 100 term pregnancies with intact membranes. Samples were collected before and immediately following ROM, and at 2 and 4 hours post-ROM. Quantitative and qualitative hCG assays were performed on all samples. Outcome measures included the detection and measured amount of hCG before and after ROM. Sensitivity, specificity and positive predictive values for the qualitative assays were determined. A total of 98% pre-ROM and 100% post-ROM qualitative assays tested positive with mean quantitative hCG levels of 181.30 mIU/mL and 208.24 mIU/mL, respectively. The qualitative post-ROM sensitivity was 100%; however, the pre-ROM specificity was only 2%. The positive predictive value for detecting ROM was 50%. Qualitative and quantitative hCG assays are not useful for determining ROM in term pregnancies.