[Ectodermal dysplasia and familial ectrodactyly].
The purpose of this report is to describe a familial observation of EEC syndrome (ectrodactyly, ectodermal dysplasia, cleft palate). The two cases, a boy and his mother, had no cleft palate but the teeth malformations were typical of this affection. The variability of the syndrome is discussed.


Expanding the role of photoselective vaporization of the prostate.
The use of the potassium-titanyl-phosphate (KTP) laser for the ablative treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) has gained wide acceptance in the urologic community. The efficacy and safety of photoselective vaporization of the prostate using 60-W or 80-W KTP have been demonstrated in multiple trials, with significant impact on special high-risk surgical populations (ie, patients with large prostates and anticoagulated patients with multiple comorbidities) with symptomatic BPH. The high-power KTP laser technique has also shown encouraging results in the management of urethral strictures. With catheter removal, improvement in voiding may not immediately occur; however, with the efficient vaporization and limited coagulation necrosis that are routinely noted with high-power KTP applications, improvement may occur in as early as a few days to 1 week. Because of the superior surgical hemostasis associated with laser prostatectomy, no restrictions on physical activity are required after the procedure, even in the immediate postoperative period.


Monte Carlo calculation of the sensitivity of a commercial dose calibrator to gamma and beta radiation.
The detection process used in a commercial dose calibrator was modeled using the GEANT 3 Monte Carlo code. Dose calibrator efficiency for gamma and beta emitters, and the response to monoenergetic photons and electrons was calculated. The model shows that beta emitters below 2.5 MeV deposit energy indirectly in the detector through bremsstrahlung produced in the chamber wall or in the source itself. Higher energy beta emitters (E > 2.5 MeV) deposit energy directly in the chamber sensitive volume, and dose calibrator sensitivity increases abruptly for these radionuclides. The Monte Carlo calculations were compared with gamma and beta emitter measurements. The calculations show that the variation in dose calibrator efficiency with measuring conditions (source volume, container diameter, container wall thickness and material, position of the source within the calibrator) is relatively small and can be considered insignificant for routine measurement applications. However, dose calibrator efficiency depends strongly on the inner-wall thickness of the detector.


Modification of the Nuss Procedure: The Single-incision Technique.
The Nuss procedure is a prevalent minimally invasive surgery for pectus excavatum. Although the Nuss procedure has the advantage of leaving less obtrusive scars, the standard technique requires at least 3 skin incisions to insert several instruments. We experienced 7 cases of the modified Nuss procedure using a single incision during a 7-year period. To facilitate passing of the bar, a traction guide was created according to our unique method. There was no need for a bar stabilizer, and no severe intraoperative complications occurred. All patients exhibited satisfactory short-term results; however, 1 patient suffered from bar rotation and required repeat surgery for fixation. Two patients underwent bar removal via the same single incision without any difficulties.


Visuo-Haptic Discrimination of Viscoelastic Materials.
In our daily lives, we interact with different types of deformable materials. Regarding their mechanical behavior, some of those materials lie in a range that is between purely elastic and purely viscous. This range of mechanical behavior is described as viscoelasticity. In certain types of haptic interactions, such as assessment of ripeness of fruit, firmness of cheese, and consistency of organ tissue, we rely heavily on our haptic perception of viscoelastic materials. The relationship between the mechanical behavior of viscoelastic materials and our perception of them has been investigated in the field of psychorheology. However, our knowledge on how we perceive viscoelastic materials is still quite limited though some research work has already been done on purely elastic and purely viscous materials. History- and frequency-dependent behavior of viscoelastic materials result in a complex time-dependent response, which requires relatively more sophisticated models to investigate their behavior than those of purely elastic and viscous materials. In this study, we model viscoelasticity using a "springpot" (i.e., fractional-order derivative element) and express its behavior in the frequency domain using two physical parameters-"magnitude" and "phase" of complex stiffness. In the frequency domain, we are able to devise signal detection experiments where we can investigate the perception of viscoelastic materials using the perceptual terms of "firmness" and "bounciness," corresponding to the physical parameters of "magnitude" and "phase." The results of our experiments show that the just-noticeable difference (JND) for bounciness increases linearly with increasing "phase," following Weber's law, while the JND for firmness is surprisingly independent of the level of "phase."


Glucose-6-phosphate dehydrogenase deficiency: a preventable cause of mental retardation.
Over two years cord blood from 27 879 babies was screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency. The overall incidence was 3.1% in boys and 1.6% in girls. Sixty nine babies had severe jaundice (bilirubin concentration greater than 380 mmol/l (20 mg/100 ml], and exchange transfusion was performed. Parents were given written and verbal instructions to avoid herbs and drugs that trigger kernicterus, which reduced the incidence of kernicterus and thereby prevented mental retardation. G6PD deficiency is common in all three ethnic groups (Malays, Chinese, and Indians) in Malaysia and screening is recommended.


Trends and drivers of marine debris on the Atlantic coast of the United States 1997-2007.
For the first time, we documented regional differences in amounts and long-term trends of marine debris along the US Atlantic coast. The Southeast Atlantic had low land-based and general-source debris loads as well as no increases despite a 19% increase in coastal population. The Northeast (8% population increase) also had low land-based and general-source debris loads and no increases. The Mid-Atlantic (10% population increase) fared the worst, with heavy land-based and general-source debris loads that increased over time. Ocean-based debris did not change in the Northeast where the fishery is relatively stable; it declined over the Mid-Atlantic and Southeast and was correlated with declining regional fisheries. Drivers, including human population, land use status, fishing activity, and oceanic current systems, had complex relationships with debris loads at local and regional scales. Management challenges remain undeniably large but solid information from long-term programs is one key to addressing this pressing pollution issue.


'Right' for publication: strategies for supporting novice writers across health and medical disciplines.
The idea that scholarly writing is an integral part of academic and clinical work is not new; however, increasing expectations that health professionals contribute to research output through publication, regardless of level of employment or experience, creates anxiety and dissonance for many novice and sometimes not-so-novice writers. Publications and the impact of scholarly work have become the key indicators not only of the performance of individual health academics, but also of health disciplines and universities more broadly. In Australia, as in many other countries, publications as the measure of research impact and outputs are expected in professional disciplines, universities and schools. Research impact is assessed and rated against other institutions and used as a means of allocating scarce research funding. Publishing has become a matter of professional reputation and sustainability. This paper reports on a project designed to enhance publication rates across health disciplines based at a rural university, where many staff members combine academic work with ongoing clinical roles. Without deliberate and focused support to enhance skills and confidence in writing it was unlikely that these academics and clinical staff members would be able to develop the kind of track record required for a successful academic career or promotion. This paper outlines the development, delivery and outcomes of this university-funded project, which drew on evidence in the literature to increase the publication rates across two Schools (Health and Medicine) at a rural university.


Electrochemical DNA-Based Immunoassay That Employs Steric Hindrance To Detect Small Molecules Directly in Whole Blood.
The development of a universal sensing mechanism for the rapid and quantitative detection of small molecules directly in whole blood would drastically impact global health by enabling disease diagnostics, monitoring, and treatment at home. We have previously shown that hybridization between a free DNA strand and its complementary surface-bound strand can be sterically hindered when the former is bound to large antibodies. Here, we exploit this effect to design a competitive antibody-based electrochemical assay, called CeSHHA, that enables the quantitative detection of small molecules directly in complex matrices, such as whole blood or soil. We discuss the importance of this inexpensive assay for point-of-care diagnosis and for treatment monitoring applications.


Eruptive disseminated superficial basal cell carcinomas 24 years after bone marrow transplantation.
Secondary cutaneous malignancies are often reported after treatment of malignant haemopathies using allogeneic bone marrow transplantation (BMT). Within the spectrum of such secondary skin carcinomas, basal cell carcinomas (BCC) appear the most frequent. We report here the case of a 67- year-old male patient who developed 24 years after BMT more than 40 superficial BCC as well as a few nodular BCC. These tumours were mainly found on the lower limbs at sites without sun exposure. The patient was treated with surgical excision of nodular BCC while photodynamic therapy was used for the superficial BCC. No recurrences were reported at 5-year follow-up. To our knowledge, this is the first case of a patient presenting eruptive and non-recurring BCC so long after BMT. Only two similar cases have been reported in other circumstances. There is no clear explanation to this peculiar non-recurrence. We speculate that repair of DNA mutations may have occurred.


Propeller-type parallel-stranded G-quadruplexes in the human c-myc promoter.
The nuclease-hypersensitivity element III1 in the c-myc promoter is a good anticancer target since it largely controls transcriptional activation of the important c-myc oncogene. Recently, the guanine-rich strand of this element has been shown to form an equilibrium between G-quadruplex structures built from two different sets of G-stretches; two models of intramolecular fold-back antiparallel-stranded G-quadruplexes, called "basket" and "chair" forms, were proposed. Here, we show by NMR that two sequences containing these two sets of G-stretches form intramolecular propeller-type parallel-stranded G-quadruplexes in K(+)-containing solution. The two structures involve a core of three stacked G-tetrads formed by four parallel G-stretches with all anti guanines and three double-chain-reversal loops bridging three G-tetrad layers. The central loop contains two or six residues, while the two other loops contain only one residue.


The relationship of affective and bodily states with goals and plans to increase physical activity: An 8-day study in students.
Planning is an important tool to translate intentions into physical activity (PA) behavior. Affective and bodily states are known to influence how much PA individuals perform, but their impact on to formulation of PA plans is not yet known. The aim of the current study is to explore the effect of within- and between-subject variations in affective and bodily states on the content of PA goals and plans. Over eight consecutive days, 362 students created action and coping plans to achieve their daily PA goals. They also reported their affective and bodily states. Generalized linear mixed effect models were used to analyze the associations between these states and the content of the goals and plans. The results showed that both between- and within-subject variations in affective and bodily states were associated with goals formulated in terms of minutes, the intensity and context of planned activities, and anticipated barriers, though more effects were found for within-subject differences. Affective and bodily states impact daily PA goals and plans, highlighting the dynamic nature of planning. Our findings can be a first step toward personalized suggestions for goals, action plans, and coping strategies that are based on individual affective and bodily states.


Multiple Organ Dysfunction: The Defining Syndrome of Sepsis.
Sepsis as a process has been recognized since the time of the Ancient Greeks. The concept has evolved recently to reflect a disease process of a severe, systemic response to infection. Acute, life-threatening but potentially reversible organ dysfunction is its hallmark, and unresolving organ dysfunction is the dominant cause of death in critical illness. Its evolution, persistence, and resolution reflect a complex interplay of factors originating in the initial inciting insult, the innate immune and metabolic response of the host, and the beneficial and harmful consequences of intensive care unit (ICU) supportive care. We describe the common clinical manifestations of the six prototypic organ system dysfunction syndromes of severe sepsis and review the associated epidemiology and suspected pathophysiology.


Do real time 'flu spotter rates warn us about impending emergency admissions and deaths?
This study aimed to determine how general practice influenza surveillance ('flu spotter) data related to hospital admissions and deaths in Scotland during the winter period. 'Flu spotter rates correlated well with influenza-related emergency admissions and deaths, and deaths from all causes, particularly during 'peak' influenza years. They may be used in a predictive model for influenza-related hospital admissions and deaths.


Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue.
Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue, and sheds light on new mechanisms of platelet activation and platelet-mediated immune and inflammatory responses.


Direct volatilization of naphthalene to the atmosphere at a phytoremediation site.
Phytoremediation systems are known to reduce groundwater contamination by at least three major mechanisms: plant uptake, phytovolatilization, and enhanced rhizosphere bioremediation. The potential for such systems to enhance a fourth remediation pathway--direct surface volatilization of contaminants through the subsurface and into the atmosphere-has not yet been investigated in the field. A vertical flux chamber was used to measure direct surface volatilization of naphthalene over nine months at a creosote-contaminated site in Oneida, Tennessee, where a phytoremediation system of poplar trees was installed in 1997. A maximum flux of 23 microg m(-2) h(-1) was measured in August 2004, and naphthalene removal by the direct volatilization pathway is estimated to be 50 g yr(-1) at this site. Results suggest that direct volatilization fluxes are most strongly affected by the groundwater level (thickness of the saturated zone), soil moisture, and changes in atmospheric pressure. At this site, transpiration and canopy interception resulting from the phytoremediation system significantly reduce the saturated thickness, increasing the vertical concentration gradient of naphthalene in the groundwater and thus increasing the upward diffusive flux of naphthalene through the subsurface. The presence of the trees, therefore, promotes direct volatilization into the atmosphere. This research represents the first known measurement of naphthalene attenuation by the direct volatilization pathway.


Idiopathic external apical root resorption: clinical report of 2 cases.
External root resorptions are characterized by progressive destruction of hard tissue due to clastic activity. This article reports 2 cases that involved the nonsurgical treatment of mandibular molars with idiopathic external root resorption. In the first case, clinical and radiographic examination showed irreversible inflammation of the pulp tissue and resorption of the distal root. Chronic inflammatory infiltrate and necrosis were identified by histopathologic examination of the pulp tissue. In the second case, inadequate endodontic treatment and a resorptive process were observed in the mesial and distal roots. In both cases, mineral trioxide aggregate (MTA) was used as the filling material. Clinical and radiographic follow-ups of 1 and 7 years, respectively, showed a favorable trend, including interruption of the resorptive process and periradicular normality. More longitudinal studies are necessary to analyze the performance of MTA in treating external root resorptions.


Process parameter effects on material removal in magnetorheological finishing of borosilicate glass.
We investigate the effects of processing parameters on material removal for borosilicate glass. Data are collected on a magnetorheological finishing (MRF) spot taking machine (STM) with a standard aqueous magnetorheological (MR) fluid. Normal and shear forces are measured simultaneously, in situ, with a dynamic dual load cell. Shear stress is found to be independent of nanodiamond concentration, penetration depth, magnetic field strength, and the relative velocity between the part and the rotating MR fluid ribbon. Shear stress, determined primarily by the material mechanical properties, dominates removal in MRF. The addition of nanodiamond abrasives greatly enhances the material removal efficiency, with the removal rate saturating at a high abrasive concentration. The volumetric removal rate (VRR) increases with penetration depth but is insensitive to magnetic field strength. The VRR is strongly correlated with the relative velocity between the ribbon and the part, as expected by the Preston equation. A modified removal rate model for MRF offers a better estimation of MRF removal capability by including nanodiamond concentration and penetration depth.


Immuno-Efficacy of a T. gondii Secreted Protein with an Altered Thrombospondin Repeat (TgSPATR) As a Novel DNA Vaccine Candidate against Acute Toxoplasmosis in BALB/c Mice.
Toxoplasma gondii (T.gondii) is distributed worldwide and infects most species of warm-blooded animals, including humans. Toxoplasmosis has serious consequences, especially in people with an impaired or immature immune system. Thus, an effective vaccine is urgently required. Secretory microneme proteins are essential for the adhesion and invasion of T. gondii. The gene encoding the microneme protein, T. gondii secreted protein with an altered thrombospondin repeat (TgSPATR), we constructed a recombinant eukaryotic plasmid, pVAX1-TgSPATR, as a DNA vaccine, injected it intramuscularly into BALB/c mice and evaluated the induced immune response. Lymphocyte proliferation assays, cytokine (IFN-γ, IL-2, IL-4, IL-10), and antibody determinations showed that mice immunized with pVAX1-TgSPATR produced humoral and mixed Th1/Th2 type cellular immune responses. The survival times of mice immunized with pVAX1-TgSPATR were also significantly prolonged (15.7 ± 1.42 days) compared with control groups, which died within 7 days of challenge (p < 0.05). The current study indicated that pVAX1-TgSPATR induce a T. gondii specific immune response and might be a promising vaccine candidate against toxoplasmosis. To the best of our knowledge, this is the first report to evaluate the immunoprotective value of TgSPATR against T. gondii.


[Morphology and clinic of ovarial teratomas (author's transl)].
This analysis covers 170 patients with teratomas from 1965-1978 in the Department of Obstetrics and Gynaecology of Heidelberg University. Malignant teratomas were found in two patients; in a special case, a "gliomatosis peritonei" was identified. The histological composition, the degree of maturity, grading and clinical staging were compared with regard to the prognosis and for obtaining an optimal therapeutic approach and procedure. Under the condition that an accurate and extensive histological diagnosis is obtained, "conservative surgery" seems to be the optimal therapy in fertile patients. In case of malignant teratoma, radical surgery followed by chemotherapy is imperative.


Characteristics of Schools with Youth Sports Concussion-Related Educational Policies and Practices.
School policies and practices designed to educate athletes, parents, and coaches about youth sports concussions may be a way to reduce concussion risk and improve both the recognition and management of concussions. Nationally representative data from the 2014 School Health Policies and Practices Study (SHPPS) were used to assess associations between school demographic characteristics (eg, school level, metropolitan status, and school type) and school policies and practices addressing youth sports concussion-related education for athletes, parents, and coaches. Overall, many schools had policies and practices that addressed youth sports concussion-related education for athletes, parents, and coaches. There was significant variability in the adoption of policies and practices by some school demographic characteristics. Middle schools, private schools, and urban schools were less likely to adopt many of the policies and practices than high schools, public schools, and rural schools, respectively. For other school characteristics, no consistent patterns of associations emerged. These findings suggest that middle, private, and urban schools, in particular, are more likely to lack youth sports concussion-related educational policies and practices and may need information or resources about the importance of education related to preventing, recognizing, and responding to concussions.


Treatment of the first tonic-clonic seizure does not affect long-term remission of epilepsy.
We followed 419 patients with a first, unprovoked, primarily or secondarily generalized tonic-clonic seizure, randomized to immediate antiepileptic treatment or to treatment only in the event of seizure recurrence. The probability of achieving a 2-year remission was 72 vs 57% at 3 months, 84 to 79% at 3 years, and 85 to 86% at 10 years (p = NS). The probability of entering 5-year remission was 47 to 40, 58 to 58, and 64 to 64% (p = NS). Early treatment does not affect the long-term prognosis of epilepsy.


Quantification and localization of kainic acid-induced neurotoxicity employing a new biomarker of cell death: cleaved microtubule-associated protein-tau (C-tau).
Previous studies of neuronal degeneration induced by the neurotoxin, kainic acid, employed silver stain techniques that are non-quantitative or ELISA measurement of the non-neuronal protein, glial fibrillary acidic protein. As previous studies employed biomarkers that were either non-quantitative or non-neuronal, the present study employed a new neuronally localized biomaker of neuronal damage, cleaved microtubule-associated protein (MAP)-tau (C-tau). The time course of kainate neurotoxicity was quantitatively determined in several brain regions in the present study employing a C-tau specific ELISA. Differences in ELISA determined regional brain levels of C-tau were compared with the density of somatodendritic C-tau labeling qualitatively determined in immunohistochemical anatomical mapping studies of kainic acid-treated animals. Immunoblot studies revealed that the C-tau antibodies employed in the present study were highly specific for proteolytic cleaved C-tau. Immunolabeling of 45 kD-50 kD C-tau proteins was observed only in brain samples from kainic acid-treated but not vehicle-treated rats. Time course studies revealed that C-tau levels determined by ELISA were maximal 3 days after kainic acid with C-tau levels increasing 26-fold in hippocampus, 16-fold in cortex and four-fold in both striatum and hypothalamus. These statistical differences in maximal C-tau levels observed in the ELISA studies were similar to differences qualitatively observed in C-tau immunohistochemical studies. C-tau immunohistochemistry revealed extensive damage in hippocampal regions CA1 and 3, moderate damage in several cortical regions and mild damage in striatum and hypothalamus. Similar cleavage of rat MAP-tau to C-tau has been reported after neuronal degeneration induced by neurotoxic doses of methamphetamine and neuronal degeneration resulting from bacterial meningitis. In humans, C-tau proteolysis has been demonstrated to be a reliable biomarker of neuronal damage in traumatic brain injury and stroke where cerebrospinal C-tau levels are correlated with patient clinical outcome. These data suggest that C-tau proteolysis may prove a reliable species independent biomarker of neuronal degeneration regardless of source of injury.


A taxonomic review of the parasitoid wasp genera Furcidentia Zettel and Pseudophanerotoma Zettel (Hymenoptera: Braconidae: Cheloninae) from the Neotropics with the description of four new species.
Furcidentia Zettel, 1990 (Braconidae: Cheloninae) from the New World has been recently recognised as a genus separate from Pseudophanerotoma Zettel, 1990. Previously known from three species, three additional new species of Furcidentia are described here from the Neotropical region: F. jenningsi sp. nov. (French Guiana), F. llama sp. nov. (Guatemala), and F. tikalensis sp. nov. (Guatemala). The species F. clypeata Zettel (Ecuador) comb. nov., F. pulchra Zettel (Costa Rica) comb. nov., and F. sharkeyi Zettel (Ecuador) comb. nov. are transferred to Furcidentia. Additionally, one new species of Pseudophanerotoma is described: P. austini sp. nov. (Guatemala), while P. paranaensis (Costa Lima) (Brazil) and P. thapsina (Walley) (Texas, USA) are redescribed and are here recorded from French Guiana for the first time, thus considerably expanding their known distribution. Redescriptions include the description of the male of P. thapsina (Walley) for the first time and of the female of P. paranaensis (Costa Lima). Identification keys to the Neotropical genera of Phanerotomini and the species of Furcidentia and Pseudophanerotoma are provided.


Factors influencing dental decision making.
In clinical decision making, dentists routinely choose between alternative treatments such as crown vs amalgam/composite buildup, root canal vs extraction, fixed bridge vs removable partial denture, and prophylaxis vs subgingival curettage or periodontal scaling. A number of technical and patient factors can influence dentists' choice of treatment in these situations; however, little is known about their relative importance. To address this issue, a list of technical (e.g., periodontal status and caries rate) and patient (e.g., cost and patient preference) factors possibly influencing choice of treatment was developed for each pair of services. Responding to a mail questionnaire, 156 general dentists in Washington State listed the top three factors influencing their choice of service in each pair. Results revealed that dentists took different factors into account in choosing among alternative treatments. Technical factors dominated over patient concerns; only about 33 percent of the dentists considered patient factors important in choosing alternative therapies. The latter group was less preventively oriented, were solo practitioners, worked longer hours, and had lower prices. Results suggest patients may have little influence on prescriptions of therapy among experienced general dentists.


Note: Improved heater design for high-temperature hollow cathodes.
We present an improved heater design for thermionic cathodes using a rhenium filament encased in a boron nitride ceramic sleeve. This heater is relatively simple to fabricate, yet has been successfully used to reliably and repeatably light a lanthanum hexaboride (LaB6) hollow cathode based on a previously published design without noticeable filament degradation over hundreds of hours of operation. The high decomposition temperature of boron nitride (2800 C for inert environments) and melting point for rhenium (3180 C) make this heater especially attractive for use with LaB6, which may require operating temperatures upwards of 1700 C. While boron nitride decomposes in air above 1000 C, the heater was used only at vacuum with an inert gas discharge, and no degradation was observed. Limitations of current state of the art cathode heaters are also discussed and compared with the rhenium-boron nitride combination.


Simultaneous Recordings of Cortical Local Field Potentials and Electrocorticograms in Response to Nociceptive Laser Stimuli from Freely Moving Rats.
Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and human studies to investigate the cortical processing of nociceptive information. These laser-evoked brain potentials (LEPs) consist of several transient responses that are time-locked to the onset of laser stimuli. However, the functional properties of the LEP responses are still largely unknown, due to the lack of a sampling technique that can simultaneously record neural activities at the surface of the cortex (i.e., electrocorticogram [ECoG] and scalp electroencephalogram [scalp EEG]) and inside the brain (i.e., local field potential [LFP]). To address this issue, we present here an animal protocol using freely moving rats. This protocol is composed of three main procedures: (1) animal preparation and surgical procedures, (2) a simultaneous recording of ECoG and LFP in response to nociceptive laser stimuli, and (3) data analysis and feature extraction. Specifically, with the help of a 3D-printed protective shell, both ECoG and LFP electrodes implanted on the rat's skull were securely held together. During data collection, laser pulses were delivered on the rat's forepaws through gaps in the bottom of the chamber when the animal was in spontaneous stillness. Ongoing white noise was played to avoid the activation of the auditory system by the laser-generated ultrasounds. As a consequence, only nociceptive responses were selectively recorded. Using the standard analytical procedures (e.g., band-pass filtering, epoch extraction, and baseline correction) to extract stimulus-related brain responses, we obtained results showing that LEPs with a high signal-to-noise ratio were simultaneously recorded from ECoG and LFP electrodes. This methodology makes the simultaneous recording of ECoG and LFP activities possible, which provides a bridge of electrocortical signals at the mesoscopic and macroscopic levels, thereby facilitating the investigation of nociceptive information processing in the brain.


Association of prostate cancer with vitamin D receptor haplotypes in African-Americans.
In previous studies, allelic variation in the 3' end of the vitamin D receptor gene was associated with increased risk of prostate cancer in white men. Several polymorphisms, including a BsmI restriction site and a poly(A) microsatellite, can be used interchangeably to mark the unidentified locus in whites. In African-Americans, however, these markers are not interchangeable, due to weaker linkage disequilibrium in this genomic region in this population. Here, we genotyped both the BsmI and poly(A) markers for 151 African-American prostate cancer cases (102 localized and 49 advanced) and 174 African-American male controls from a large epidemiological cohort. A direct haplotyping procedure was devised to determine BsmI/poly(A) haplotypes for double heterozygotes so that haplotypes could be used as allelic markers in standard logistic regression analyses. Using BsmI alone, b alleles were associated with a 2-fold decrease in risk of advanced prostate cancer. The association was, however, confined to haplotypes carrying a long (L) allele of the poly(A) microsatellite. BL and bL haplotypes were associated with increased and decreased risk, respectively, whereas neither BS nor bS haplotypes were associated with prostate cancer risk. An allelic variant that confers increased risk of advanced prostate cancer appears to be associated with the BsmI/poly(A) BL haplotype in African-Americans.


Literacy Skill Differences between Adult Native English and Native Spanish Speakers.
The goal of this study was to compare the literacy skills of adult native English and native Spanish ABE speakers. Participants were 169 native English speakers and 124 native Spanish speakers recruited from five prior research projects. The results showed that the native Spanish speakers were less skilled on morphology and passage comprehension tasks but were equally skilled on the phonology and vocabulary tasks. Morphology, coupled with phonology, was a stronger predictor of vocabulary and comprehension abilities for the native Spanish speakers, which suggests that instruction focused on morphology is likely to have a greater impact on this group.


Relationship between plasma iron concentration and gastric pH in captive adult bottlenose dolphins (Tursiops truncatus).
To determine the correlation between plasma iron concentrations and gastric pH in a population of captive Atlantic bottlenose dolphins (Tursiops truncatus). 6 adult female dolphins that ranged from 16 to 30 years of age. Blood and gastric samples were collected from each dolphin to allow measurement of plasma iron concentrations and gastric pH, respectively. Samples were collected each month for 12 months. Within each dolphin, plasma iron concentrations and gastric pH did not differ significantly over time. There was a strong negative correlation (r = -0.85) between plasma iron concentration and gastric pH, which suggested that dolphins with a lower gastric pH had a higher plasma iron concentration. Analysis of results reported here suggested that gastric pH may play an important role in iron absorption in dolphins.


[Renal effects of captopril in chronic heart failure].
The effect of captopril on renal function, central hemodynamics and the hormonal status was studied in 14 patients with chronic congestive heart failure in single administration of the drug at a dose of 25 mg and during short-term course therapy at a daily dose of 75 mg for 7 days. Captopril single administration was shown to cause an increase in natriuresis by 121% and diuresis by 120%. Correlation analysis showed that the natriuretic effect of captopril resulted from a decrease in tubular sodium reabsorption which, in its turn, was determined by a decrease in the production of angiotensin II and changes of pritubular circulation. Seven-day course therapy was accompanied by the patients' improved general status, improved indices of hemodynamics, and better tolerance to physical exercise. At the same time diuresis and renal excretion of sodium were above the basal level by 113 and 86%, respectively. It can be assumed that this natriuretic effect was determined by the suppression of angiotensin II, aldosterone and probably norepinephrine and vasopressin production. The analysis has shown that a favorable captopril renal effect is not mediated through improved central hemodynamics but results from changes of the hormonal and neurohumoral status.


Common metabolic profile in infants indicating impaired cobalamin status responds to cobalamin supplementation.
A metabolic profile consistent with impaired cobalamin status is prevalent in breastfed infants. We investigated whether this profile reflects immature organ systems or impaired cobalamin status. In a single-center, randomized, placebo-controlled trial, we studied 107 six-week-old infants. The infants were randomly assigned to receive either an intramuscular injection of 400 mug of cobalamin or no intervention. Concentrations of cobalamin and folate in serum and total homocysteine, methylmalonic acid, and cystathionine in plasma were determined at enrollment and at the age of 4 months. There were no significant differences between the intervention group (n = 54) and the control group (n = 53) in the concentrations of any vitamin marker at baseline (6 weeks). At 4 months, the supplement-treated infants had a 75% higher median serum cobalamin level and remarkable reductions in median plasma total homocysteine (from 7.46 to 4.57 micromol/L) and methylmalonic acid (from 0.58 to 0.20 micromol/L) levels, whereas levels of both metabolites were essentially unchanged during the follow-up period in the control group. Cobalamin supplementation changed all markers of impaired cobalamin status (low cobalamin, high total homocysteine, and high methylmalonic acid levels) toward a profile observed in cobalamin-replete older children and adults. Therefore, the high total homocysteine and methylmalonic acid levels reported for a large fraction of infants reflect not immature metabolism but rather insufficient cobalamin levels to fully sustain cobalamin-dependent reactions fully.


Genomic analyses of multidrug-resistant Salmonella Indiana, Typhimurium, and Enteritidis isolates using MinION and MiSeq sequencing technologies.
We sequenced 25 isolates of phenotypically multidrug-resistant Salmonella Indiana (n = 11), Typhimurium (n = 8), and Enteritidis (n = 6) using both MinION long-read [SQK-LSK109 and flow cell (R9.4.1)] and MiSeq short-read (Nextera XT and MiSeq Reagent Kit v2) sequencing technologies to determine the advantages of each approach in terms of the characteristics of genome structure, antimicrobial resistance (AMR), virulence potential, whole-genome phylogeny, and pan-genome. The MinION reads were base-called in real-time using MinKnow 3.4.8 integrated with Guppy 3.0.7. The long-read-only assembly, Illumina-only assembly, and hybrid assembly pipelines of Unicycler 0.4.8 were used to generate the MinION, MiSeq, and hybrid assemblies, respectively. The MinION assemblies were highly contiguous compared to the MiSeq assemblies but lacked accuracy, a deficiency that was mitigated by adding the MiSeq short reads through the Unicycler hybrid assembly which corrected erroneous single nucleotide polymorphisms (SNPs). The MinION assemblies provided similar predictions of AMR and virulence potential compared to the MiSeq and hybrid assemblies, although they produced more total false negatives of AMR genotypes, primarily due to failure in identifying tetracycline resistance genes in 11 of the 19 MinION assemblies of tetracycline-resistant isolates. The MinION assemblies displayed a large genetic distance from their corresponding MiSeq and hybrid assemblies on the whole-genome phylogenetic tree, indicating that the lower read accuracy of MinION sequencing caused incorrect clustering. The pan-genome of the MinION assemblies contained significantly more accessory genes and less core genes compared to the MiSeq and hybrid assemblies, suggesting that although these assemblies were more contiguous, their sequencing errors reduced accurate genome annotations. Our research demonstrates that MinION sequencing by itself provides an efficient assessment of the genome structure, antimicrobial resistance, and virulence potential of Salmonella; however, it is not sufficient for whole-genome phylogenetic and pan-genome analyses. MinION in combination with MiSeq facilitated the most accurate genomic analyses.


Interpretable Topic Features for Post-ICU Mortality Prediction.
Electronic health records provide valuable resources for understanding the correlation between various diseases and mortality. The analysis of post-discharge mortality is critical for healthcare professionals to follow up potential causes of death after a patient is discharged from the hospital and give prompt treatment. Moreover, it may reduce the cost derived from readmissions and improve the quality of healthcare. Our work focused on post-discharge ICU mortality prediction. In addition to features derived from physiological measurements, we incorporated ICD-9-CM hierarchy into Bayesian topic model learning and extracted topic features from medical notes. We achieved highest AUCs of 0.835 and 0.829 for 30-day and 6-month post-discharge mortality prediction using baseline and topic proportions derived from Labeled-LDA. Moreover, our work emphasized the interpretability of topic features derived from topic model which may facilitates the understanding and investigation of the complexity between mortality and diseases.


Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds.
Many naturally occurring substances, traditionally used in popular medicines around the world, contain the coumarin moiety. Coumarin represents a privileged scaffold for medicinal chemists, because of its peculiar physicochemical features, and the versatile and easy synthetic transformation into a large variety of functionalized coumarins. As a consequence, a huge number of coumarin derivatives have been designed, synthesized, and tested to address many pharmacological targets in a selective way, e.g., selective enzyme inhibitors, and more recently, a number of selected targets (multitarget ligands) involved in multifactorial diseases, such as Alzheimer's and Parkinson's diseases. In this review an overview of the most recent synthetic pathways leading to mono- and polyfunctionalized coumarins will be presented, along with the main biological pathways of their biosynthesis and metabolic transformations. The many existing and recent reviews in the field prompted us to make some drastic selections, and therefore, the review is focused on monoamine oxidase, cholinesterase, and aromatase inhibitors, and on multitarget coumarins acting on selected targets of neurodegenerative diseases.


Health impacts due to particulate air pollution in Volos City, Greece.
There is great consensus among the scientific community that suspended particulate matter is considered as one of the most harmful pollutants, particularly the inhalable particulate matter with aerodynamic diameter less than 10 μm (PM10) causing respiratory health problems and heart disorders. Average daily concentrations exceeding established standard values appear, among other cases, to be the main cause of such episodes, especially during Saharan dust episodes, a natural phenomenon that degrades air quality in the urban area of Volos. In this study the AirQ2.2.3 model, developed by the World Health Organization (WHO) European Center for Environment and Health, was used to evaluate adverse health effects by PM10 pollution in the city of Volos during a 5-year period (2007-2011). Volos is a coastal medium size city in the Thessaly region. The city is located on the northern side of the Gulf of Pagassitikos, on the east coast of Central Greece. Air pollution data were obtained by a fully automated monitoring station, which was established by the Municipal Water Supply and Sewage Department in the Greater Area of Volos, located in the centre of the city. The results of the current study indicate that when the mean annual PM10 concentration exceeds the corresponding European Union (EU) threshold value, the number of hospital admissions for respiratory disease (HARD) is increased by 25% on average. There is also an estimated increase of about 2.5% in HARD compared to the expected annual HARD cases for Volos. Finally, a strong correlation was found between the number of days exceeding the EU daily threshold concentration ([PM10] ≥ 50 μg m(-3)) and the annual HARD cases.


Antiretroviral medication support practices among partners of men who have sex with men: a qualitative study.
The aim of this qualitative study is to describe the practical support for antiretroviral therapy (ART) adherence offered by partners of men with HIV. Twenty couples in which at least one partner was HIV positive and on ART were interviewed separately about their involvement in their partners' ART adherence. The interview elicited narratives of specific recent events around taking medication, as well as accounts of what the participants usually did to support their partners' adherence. Three members of the qualitative team coded and verified the interviews for adherence support practices. Partners offered a wide range of kinds of practical support. Reminding included (1) regular reminding that was habitually offered, (2) situational reminding adapted to changing circumstances, and (3) intensive reminding, either regular (i.e., nagging) or situational. Instrumental helping involved monitoring medication adherence, bringing or setting out medications at the dose time, organizing the pills, and requesting and/or picking up refills. Coaching involved situational problem-solving and shaping behavior by reinforcing incremental gains and offering affirmations. Findings demonstrate a range of support practices for ART adherence, often tailored to partners' styles or to the changing process of adherence. By examining narratives of support transactions as they occurred, the study discriminated among the different dimensions, forms, sources and contexts of social support. These distinctions, often neglected in social support research, have implications for HIV care and research.


Atlantoaxial rotatory fixation in a case of tubercular lymphadenitis.
Atlantoaxial fixation is a relatively rare cause of torticollis which may be easily missed in practice. Early diagnosis is important as this indicates a compromised atlantoaxial complex with the potential to cause neural damage or even death. Here, we report a case of atlantoaxial rotatory fixation in a 13 yr old male with torticollis for two years and history of defaulting treatment for tubercular lymphadenitis. In this case, the odontoid peg view revealed asymmetric distance between the odontoid and lateral mass of atlas which was confirmed with Fluoroscopy and Computed Tomography (CT) scan. Magnetic Resonance Imaging (MRI) was also done which showed hyperintensity in alar ligaments with posterior inclination of the odontoid peg along with cervical lymphadenopathy.


(18)O/(16)O isotope effect on miscibility of isobutyric acid with water.
The miscibility of isobutyric acid with water and the influence of the isotope substitution of oxygen (16O/18O) in water over a broad concentration range are reported. The system exhibits a phase diagram with an upper critical solution temperature (UCST) and a visible isotope effect thereon. The oxygen isotope substitution decreases the UCST, leading to better miscibility of isobutyric acid with water. The isotope shift, DeltaTc = Tc(18O) - Tc(16O), extrapolated to the 100% enrichment in 18O, is equal to -1.15 K; hence it is much smaller and opposite to that found for deuterium substitution. The origin of the observed miscibility isotope effect has been qualitatively discussed in terms of the condensed-phase isotope effect theory.


Improved methodology to compute the intrinsic friction coefficient at solid-liquid interfaces.
In this work, we propose an improved methodology to compute the intrinsic friction coefficient at the liquid-solid (L-S) interface based on the theoretical model developed by Hansen et al. [Phys. Rev. E 84, 016313 (2011)]. Using equilibrium molecular dynamics, we apply our method to estimate the interfacial friction for a simple Lennard-Jones system of argon confined between graphene sheets and a system of water confined between graphene sheets. Our new method shows smaller statistical errors for the friction coefficient than the previous procedure suggested by Hansen et al. Since we only use the interfacial particles, the interfacial friction calculated using our method is solely due to the wall-fluid interactions and is devoid of bulk fluid contributions. The intrinsic nature of the friction coefficient has been validated by measuring the friction coefficient at different interfaces and channel sizes and against direct non-equilibrium molecular dynamics measurements. Our improved methodology is found to be more reliable than the existing equilibrium and non-equilibrium methods and does not suffer from the well-known convergence and correlation-time ambiguities in the methods formulated along Green-Kubo-like ideas.


Bioscore: A Staging System for Breast Cancer Patients that Reflects the Prognostic Significance of Underlying Tumor Biology.
Biologic factors guide treatment decisions and have a significant impact on prognosis for breast cancer patients. This study was undertaken to develop a staging system incorporating biologic factors in addition to standard anatomic factors in the American Joint Committee on Cancer (AJCC) pathologic stage (PS) to assess disease-specific survival (DSS). Overall, 3327 patients treated with surgery as an initial intervention at MD Anderson Cancer Center from 2007 to 2013 were identified. Multivariate analyses of factors, including PS, T stage (T), nodal stage (N), grade (G), estrogen receptor (ER) status (E) and human epidermal growth factor receptor (HER2) status (H) were performed to identify associations with DSS. A score of 0-4 was assigned for each factor by considering the hazard ratio magnitude. Multiple staging system models were then constructed: PS, PS + G, PS + G + E, PS + G + E + H, T + N, T + N + G, T + N + G + E, and T + N + G + E + H. Model performance was quantified using Harrell's concordance index, and the Akaike Information Criterion (AIC) was used to compare model fits. Comparable cases from California (n = 67,944) were used for validation. Median follow-up was 5.0 years (range 0.1-8.8) and 5-year DSS was 97.9% (95% confidence interval 97.3-98.4). Models incorporating grade, ER status, and HER2 status were most precise with identical C-index (0.81) and comparable AIC (994.9 for PS + G + E + H and 987.8 for T + N + G + E + H). Both models were externally validated. These results confirm the importance of biologic factors in determining prognosis for breast cancer patients. We propose the Bioscore, which incorporates grade, ER and HER2 status with AJCC PS, to provide more refined stratification of breast cancer patients undergoing surgery as an initial intervention with respect to DSS.


Intestinal concentrations of pancreatic enzymes following pancreatic replacement therapy.
The activities of amylase, lipase, phospholipase, and trypsin in four commercially available preparations of pancreatin with different galenic and adjunctive protective properties were estimated in vitro, using human small-intestinal juice as the incubation medium. These preparations were administered to healthy subjects and to patients with severe pancreatic insufficiency, and their ability to increase the intestinal concentrations of pancreatic enzymes was evaluated. The relations between in vitro and in vivo activities were also studied. In vitro testing showed that the preparations contained high but varying activities of enzymes, with the greatest variations in lipase and trypsin. Pancreatin in the form of tablets, with or without protective measures against acid, did not cause any apparent increase in the activities of pancreatic enzymes in the upper part of the gut in patients with pancreatic insufficiency. Granulated pancreatin, on the other hand, brought about an increase in the activities of amylase, phospholipase, lipase, and trypsin. Relatively higher activities of the enzymes in granulated form reached the small intestine as compared with those of the tablets.


[Influence of cefoperazone on the fecal flora in children].
A differential quantitative study was used to evaluate the effects of parenteral cefoperazone upon children's fecal flora. Fecal specimens were obtained from 16 patients, before, during and after therapy. Cefoperazone therapy was associated with major changes in fecal flora. There was marked reduction or suppression to undetectable levels of Enterobacteria, Staphylococci and Streptococci in 13 patients. During therapy, yeasts were selected or acquired in 7 cases. 5 to 10 days after cefoperazone was discontinued, the fecal flora was virtually the same as before treatment. Thus, cefoperazone should prove very useful in the treatment of septicemia due to intestinal overgrowth.


Mechanisms of fever production and lysis: lessons from experimental LPS fever.
Fever is a cardinal symptom of infectious or inflammatory insults, but it can also arise from noninfectious causes. The fever-inducing agent that has been used most frequently in experimental studies designed to characterize the physiological, immunological and neuroendocrine processes and to identify the neuronal circuits that underlie the manifestation of the febrile response is lipopolysaccharide (LPS). Our knowledge of the mechanisms of fever production and lysis is largely based on this model. Fever is usually initiated in the periphery of the challenged host by the immediate activation of the innate immune system by LPS, specifically of the complement (C) cascade and Toll-like receptors. The first results in the immediate generation of the C component C5a and the subsequent rapid production of prostaglandin E2 (PGE2). The second, occurring after some delay, induces the further production of PGE2 by induction of its synthesizing enzymes and transcription and translation of proinflammatory cytokines. The Kupffer cells (Kc) of the liver seem to be essential for these initial processes. The subsequent transfer of the pyrogenic message from the periphery to the brain is achieved by neuronal and humoral mechanisms. These pathways subserve the genesis of early (neuronal signals) and late (humoral signals) phases of the characteristically biphasic febrile response to LPS. During the course of fever, counterinflammatory factors, "endogenous antipyretics," are elaborated peripherally and centrally to limit fever in strength and duration. The multiple interacting pro- and antipyretic signals and their mechanistic effects that underlie endotoxic fever are the subjects of this review.


The role of triage in the prevention and control of COVID-19.
To prevent and control public health emergencies, we set up a prescreening and triage workflow and analyzed the effects on coronavirus disease 2019 (COVID-19). In accordance with the requirements of the level 1 emergency response of public health emergencies in Shaanxi Province, China, a triage process for COVID-19 was established to guide patients through a 4-level triage process during their hospital visits. The diagnosis of COVID-19 was based on positive COVID-19 nucleic acid testing according to the unified triage standards of the Guidelines for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (Trial version 4),4 issued by the National Health Commission of the People's Republic of China. The screened rate of suspected COVID-19 was 1.63% (4 of 246) in the general fever outpatient clinic and 8.28% (13 of 157) in the COVID-19 outpatient clinic, and they showed a significant difference (P = .00). The triage procedure effectively screened the patients and identified the high-risk population.


Acute kidney injury: prevention and recognition.
Acute kidney injury (AKI) is common and often preventable. Nurses should be able to recognise it and respond when it occurs. Through prevention or early detection, nurses can help to reduce morbidity and mortality associated with AKI, improving patients' quality of life and reducing the financial impact of AKI on the NHS.


ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup.
The commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. We genotyped 64 PanNETs and found 58% carry ATRX, DAXX, and MEN1 mutations (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis to reveal two distinct subgroups with one consisting entirely of A-D-M mutant PanNETs. Two genes differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha-cells (FDR q-value < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells.


Charge equilibration between two distinct sites in double helical DNA.
DNA assemblies containing a pendant dipyridophenazine complex of Ru(II) along with two oxidative traps, a site containing the nucleoside analog methylindole (5'-GMG-3') and a 5'-GGG-3' site, have been constructed to explore long-range charge transport through the base pair stack. With these chemically well defined assemblies, in combination with the flash/quench technique, formation of the methylindole cation radical and the neutral guanine radical is monitored directly by using transient absorption spectroscopy, and yields of oxidative damage are quantitated biochemically by gel electrophoresis. In these assemblies the base radicals form with a rate of > or =10(7) s(-1). The rate of base radical formation does not change upon the addition of a second radical trap, the 5'-GGG-3' site; however, the yield of methylindole oxidation is significantly lower. This observation indicates that the 5'-GGG-3' site is effective in competing for the migrating charge and provides a second trapping site. Switching the orientation of the two trapping sites does not affect the yield of oxidized products at either site. Therefore, in DNA both forward and reverse charge transport occur so as to provide equilibration across the duplex on a timescale that is fast compared with trapping at a particular site. Further evidence of charge equilibration results from incorporating an intervening base-stacking perturbation and monitoring the fate of the injected charge. These experiments underscore the dynamic nature of DNA charge transport and reveal the importance of considering radical propagation in both directions along the DNA duplex.


LCD Monitors as an Alternative for Precision Demanding Visual Psychophysical Experiments.
Precise timing and presentation of stimuli is critical in vision research, still, the limiting factor in successful recognition is often the monitor itself that is used to present the stimuli. The most widespread method is the use of monitors controlled by personal computers. Traditionally, most experiments used cathode-ray tubes but they are more and more difficult to access, and instead, liquid-crystal displays are getting more and more popular. The two types have fundamentally different working principles and limitations in displaying the stimulus.In our experiments, the temporal precision of the stimulus presentation was in focus. We investigated whether liquid-crystal displays, which are not considered to be fit to display fast successive stimuli, can represent an alternative choice for cathode-ray tubes. We used the double flash and the flicker illusion to compare the technical capabilities of the two monitor types. These illusions not only do require a precise timing but also a very short exposure to the stimuli. At the same time, the interstimulus interval is also of extreme importance. In addition, these illusions require peripheral stimulation of the retina, which is more sensitive to the temporal aspects of the visual stimulus. On the basis of previous studies and our own psychophysical results, we suggest that liquid-crystal displays might be a good alternative for precise, frame-to-frame stimulus presentation even if parts of the stimuli are projected on the peripheral retina.


Long-term outcomes and dynamics of mutants associated with lamivudine-adefovir rescue therapy in patients with lamivudine-resistant chronic hepatitis B.
To investigate the association between the baseline profiles and dynamics of hepatitis B virus (HBV) DNA polymerase gene mutations and the long-term virological response of lamivudine (LAM)-adefovir (ADV) combination therapy in patients with LAM-resistant chronic hepatitis B. Seventy-five patients who received LAM-ADV combination therapy for more than 12 months were analyzed. Restriction fragment mass polymorphism assays were used to detect and monitor the dynamics of LAM- and ADV-resistant mutations. The median duration of LAMADV combination therapy was 26 months (range, 12 to 58 months). The baseline mutation profiles, rtM204I (p=0.992), rtM204I/V (p=0.177), and rtL180M (p=0.051), were not correlated with the cumulative virological response, and the baseline HBV DNA level (p=0.032) was the only independent predictive factor for cumulative virological response. Tests for LAM- and ADV-resistant mutations were performed in 12 suboptimal responders in weeks 48 and 96. The population of rtM204 mutants persisted or increased in 8 of 12 patients, and rtA181T mutants newly emerged as a minor population in four patients until 96 weeks. Nevertheless, the viral loads progressively decreased during rescue therapy, and these dynamics did not correlate with virological response. The baseline profile and dynamics of LAM-resistant mutations during LAM-ADV combination therapy are not associated with a virological response.


Photofragmentation dynamics of N,N-dimethylformamide following excitation at 193 nm.
N,N-dimethylformamide, HCON(CH3)2, is a useful model compound for investigating the peptide bond photofragmentation dynamics. We report data from a comprehensive experimental and theoretical study into the photofragmentation dynamics of N,N-dimethylformamide in the gas phase at 193 nm. Through a combination of velocity-map imaging and hydrogen atom Rydberg tagging photofragment translational spectroscopy we have identified two primary fragmentation channels, namely, fission of the N-CO "peptide" bond and N-CH3 bond fission leading to the loss of CH3. The possible fragmentation channels leading to the observed products are rationalised with recourse to CASPT2 calculations of the ground and first few excited-state potential energy curves along the relevant dissociation coordinates, and the results are compared with the data from previous experimental and theoretical studies on the same system.


Transthyretin Cardiac Amyloidosis and Novel Therapies to Treat This Not-so-rare Cause of Cardiomyopathy.
Transthyretin cardiac amyloidosis (ATTR-CA) is typically a late-onset disease caused by the deposit of transthyretin amyloid fibrils throughout the heart. When this occurs, various cardiac sequelae can develop, including hypotension, conduction abnormalities, and valvular lesions. The cardiomyopathy caused by ATTR-CA (ATTR-CM) has proven difficult to treat. Until recently, symptomatic management was the only therapeutic option, and many therapies used to treat congestive heart failure were ineffective or even detrimental to patients with ATTR-CM. In addition, treatment was limited to heart and liver transplantation. As a result, prognosis was poor. Recently, a few drug therapies have come to light as potential treatment modalities for ATTR-CM, most notably tafamidis, sold under the brand names Vyndaqel and Vyndamax. After the phase III Transthyretin Amyloidosis Cardiomyopathy trial displayed the drug's efficacy, it was given breakthrough therapy designation and was approved by the Food and Drug Administration on May 6, 2019, for the treatment of ATTR-CA. This novel therapy, as well as various other therapies in the pipeline, such as inotersen and patisiran, provide hope where, until recently, there was little. Unfortunately, the exorbitant cost of these new therapies may present a barrier to long-term treatment for some patients. However, by further improving diagnostic algorithms and incorporating these new treatments into our existing therapeutic modalities, patients with ATTR-CA should be able to live far longer than previously expected. Finally, further research combining these novel treatment modalities must be done, as they may prove to be additive or even synergistic in their treatment of ATTR amyloidosis.


Rotational Motion of a Solute Molecule in a Highly Viscous Liquid Studied by 13C NMR: 1,3-Dibromoadamantane in Polymeric Chlorotrifluoroethene
The viscosity-dependent retarding effect of a polymeric solvent on the rotation of small solute molecules is investigated by 13C NMR relaxation measurements. It is found that the relaxation data of 1,3-dibromoadamantane in highly viscous polymeric chlorotrifluoroethene can be explained neither by isotropic nor by realistic anisotropic tumbling in a single environment. The experimental data are rationalized in terms of fast exchange between at least two environments with correlation times differing by up to two orders of magnitude. The study shows that a uniform retardation of molecular tumbling by a polymeric solvent, desirable for shifting the NMR observation window in studies of intramolecular mobility, is not always feasible. Copyright 1998 Academic Press.


Negative trans-acting mechanisms controlling expression of platelet-derived growth factor A and B MRNA in somatic cell hybrids.
We have studied a human malignant melanoma cell line (WM115) which expresses high levels of PDGFA and PDGFB mRNAs, a hamster fibroblast cell line (Wq3H) which lacks PDGFB and has a very low expression of PDGFA mRNA, and hybrids between these cell lines. The PDGFA and PDGFB mRNA expression in the hybrid cells was markedly suppressed, indicating that the melanoma PDGF genes are controlled in the hybrid cells by negative factors/mechanisms contributed by the fibroblast genome. The melanoma but not the fibroblast PDGFB mRNA was induced by cycloheximide in the hybrid cells, indicating that the fibroblast and the melanoma PDGFB genes are regulated differently despite their presence in the same intracellular environment.


[Incidence of adverse medical events in the neonatal intensive care unit with the help of a global trigger tool].
Identification and monitoring of the frequency of adverse medical events are important in the organization of the patient's safety system in the intensive care units (ICU). The consistent and accurate identification of adverse events remains a problem for most medical institutions, even in developed countries of the world. To determine the frequency of adverse medical events in the NICU by using Global and Pediatric Trigger Instruments. To achieve the goal, the cross-sectional study was conducted in which in retrospect analyzed 160 newborn development records which were treated in the ICU of the newborn in the perinatal center of the M.V. Sklifosovsky Poltava Regional Clinical Hospital in 2016 to identify in them certain neonatal triggers. In 21.3% of newborns, after detecting the triggers of the "Care" module, the hospital infection was confirmed, which we regarded as medical adverse event. The trigger "Infiltration / extravasation" of the same module was detected in 1.9% medical records. Triggers "Glucose less than 3.0 mmol / L after 48 hours from birth", "Increase in creatinine" and trigger "deviation of electrolytes" of the module "Laboratory" were accordingly found in 21.9%, 6.3% and 11.3% medical records of newborns. Trigger tool is an effective way to identify adverse events that cause to patient harm. Our results can form the basis for the development of a national neonatal trigger instrument that will effectively monitor the frequency of such events in the ICU of newborn.


Effects of exercise interventions during different treatments in breast cancer.
Previous findings suggest that exercise is a safe and efficacious means of improving physiological and psychosocial outcomes in female breast cancer survivors. To date, most research has focused on post-treatment interventions. However, given that the type and severity of treatment-related adverse effects may be dependent on the type of treatment, and that the effects are substantially more pronounced during treatment, an assessment of the safety and efficacy of exercise during treatment is warranted. In this review, we present and evaluate the results of randomized controlled trials (RCTs) conducted during breast cancer treatment. We conducted literature searches to identify studies examining exercise interventions in breast cancer patients who were undergoing chemotherapy or radiation. Data were extracted on physiological and psychosocial outcomes. Cohen's d effect sizes were calculated for each outcome. A total of 17 studies involving 1,175 participants undergoing active cancer therapy met the inclusion criteria. Findings revealed that, on average, exercise interventions resulted in moderate to large improvements in muscular strength: resistance exercise (RE, 𝑑 = 0.86), aerobic exercise (AE, 𝑑 = 0.55), small to moderate improvements in cardiovascular functioning (RE, 𝑑 = 0.45; AE, 𝑑 = 0.17, combination exercise (COMB, 𝑑 = 0.31) and quality of life (QoL; RE, 𝑑 = 0.30; AE, 𝑑 = 0.50; COMB, 𝑑 = 0.63). The results of this review suggest that exercise is a safe, feasible, and efficacious intervention in breast cancer patients who are undergoing different types of treatment. Additional research addressing the different modes of exercise during each type of treatment is warranted to assess the comparable efficacy of the various exercise modes during established breast cancer treatments.


CINI's approaches to intervention: an innovative strategy to combat malnutrition in India.
The Child in Need Institute (CINI) has been working toward sustainable health and nutrition development for women and children for the last twenty-six years. During the initial stages, the Institute focused on treatment and prevention of malnutrition in children under five years of age. Over the years, the program strategies have shifted to a more holistic lifecycle approach. This approach targets individuals during crucial periods of their lives--pregnant women, children (0-2 years of age) and adolescents (10-19 years of age)--as well as other vulnerable segments of the population. To reach out to these target groups, the Institute uses a three-pronged strategy that includes case management, behavior change communication, and linkage formation. Programs are either community- or center-based depending upon the need of the populations. CINI's current strategy has shown positive trends in improving the health and nutrition status of women, children, and adolescents in the community. Results include reduction of low birth weight babies, increase in proper antenatal care, reduction of severely malnourished children, decrease in maternal and infant mortality and morbidity rates, and improvement in community involvement in all reproductive and child health programs. CINI is currently monitoring its performance and activities to carry out operations research for providing further evidence for the effectiveness of its interventions.


Rapid determination of alkaline phosphatase reactivation.
A study was conducted to determine the feasibility of using the qualitative screening method specifying phenolphthalein monophosphate for differentiating reactivated and residual alkaline phosphatase activity. The relative increase in activity of the enzyme in the presence of MgCl2 serves to distinguish reactivated and residual alkaline phosphatase activity. Ten samples each of pasteurized (172 degrees F for 24 sec), sterilized (about 300 degrees F for a minimum of 2 sec) half-and-half and heavy cream were analyzed. Most samples yielded negative results initially but demonstrated activity after incubation 1 hr at 34 degrees C. The average values in terms of + marks, for the half and half and heavy cream in samples without MgCl2 were less than 1 and 2.4, respectively; for samples treated with MgCl2, the values were 2.18 and 4.6, respectively, indicating reactivated phosphatase activity. In samples containing various levels of raw milk, the activity observed in the diluted, Mg2+-containing samples was less than in the undiluted samples containing no Mg, indicating residual phosphatase activity.


Identification of a glycine-like fragment on the strychnine molecule.
Strychnine, a complex molecule, antagonizes in some unknown manner the action of glycine, an important inhibitory neurotransmitter in the spinal cord and brainstem of many vertebrates. To help understand the mechanism of this antagonism, we have employed modern computational methods to assess the similarities between these seemingly different molecules. An exhaustive comparison of topological and electronic features of both molecules was made. We have successfully located a glycine-like fragment in the strychnine molecule that, when compared to glycine, exhibits both topological and electronic charge congruence. The successful location of this glycine-like fragment allows us to speculate how the large strychnine molecule assumes its role as an antagonist against the inhibitory action of glycine, the simplest amino acid.


Stat3 activation by Src induces specific gene regulation and is required for cell transformation.
While signal transducers and activators of transcription (STATs) were originally discovered as intracellular effectors of normal signaling by cytokines, increasing evidence also points to a role for STAT transcription factors in oncogenesis. Previous studies have demonstrated that one STAT family member, Stat3, possesses constitutively elevated tyrosine phosphorylation and DNA-binding activity in fibroblasts stably transformed by the Src oncoprotein. To determine if this Stat3 activation by Src could induce Stat3-mediated gene expression, luciferase reporter constructs based on synthetic and authentic promoters were transfected into NIH 3T3 cells. Activation of endogenous cellular Stat3 by the Src oncoprotein induced gene expression through a Stat3-specific binding element (TTCCCGAA) of the C-reactive protein gene promoter. A naturally occurring splice variant of human Stat3 protein, Stat3beta, with a deletion in the C-terminal transactivation domain abolished this gene induction in a dominant negative manner. Expression of Stat3beta did not have any effect on a reporter construct based on the c-fos serum response element, which is not dependent on Stat3 signaling, indicating that Stat3beta does not nonspecifically inhibit other signaling pathways or Src function. Transfection of vectors expressing Stat3beta together with Src blocked cell transformation by Src as measured in a quantitative focus formation assay using NIH 3T3 cells. By contrast, Stat3beta had a much less pronounced effect on focus formation induced by the Ras oncoprotein, which does not activate Stat3 signaling. In addition, three independent clones of NIH 3T3 cells stably overexpressing Stat3beta were generated and characterized, demonstrating that Stat3beta overexpression does not have a toxic effect on cell viability. These Stat3beta-overexpressing clones were shown to be deficient in Stat3-mediated signaling and refractory to Src-induced cell transformation. We conclude that Stat3 activation by the Src oncoprotein leads to specific gene regulation and that Stat3 is one of the critical signaling pathways involved in Src oncogenesis. Our findings provide evidence that oncogenesis-associated activation of Stat3 signaling is part of the process of malignant transformation.


Predictive value of combining leucocyte and platelet counts for mortality in ST-segment elevation myocardial infarction patients after percutaneous coronary intervention treatment in Chinese population: a retrospective cohort study.
Risk stratification is challenging in patients with acute ST segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). We investigated the prognostic value of a novel score system combining leucocyte and platelet counts (COL-P) scores for in-hospital and long-term adverse outcomes. This was a retrospective cohort study of patients with STEMI. First Affiliated Hospital of Xinjiang Medical University. A total of 854 STEMI patients with primary PCI were included in this study from November 2009 and December 2015. Major adverse cardiovascular events (MACEs). The patients were divided into three groups according to the COL-P scores (0, 1 and 2). Cox regression analysis was used to investigate the relation between adverse outcomes and the COL-P score in patients with STEMI. A total of 44 patients died in hospital, and 99 within 3-year follow-up after discharge. The in-hospital and 3-year mortality and MACEs were higher in patients with higher COL-P score. Multivariable Cox regression indicated COL-P score was independently associated with long-term mortality (COL-P 1 vs COL-P 0: HR 2.07, 95% CI 1.016 to 5.567, p=0.005; COL-P 2 vs COL-P 0: HR 5.02, 95% CI 1.990 to 9.041, p<0.001). The COL-P score was a useful risk system for stratifying high-risk patients with STEMI after primary PCI.


Experimental evidence for anisotropic double exchange interaction driven anisotropic transport in manganite heterostructures.
An anisotropic double exchange interaction driven giant transport anisotropy is demonstrated in a canonic double exchange system of La2/3Sr1/3MnO3 ultrathin films epitaxially grown on NdGaO3 (110) substrates. The oxygen octahedral coupling at the La2/3Sr1/3MnO3/NdGaO3 interface induces a planar anisotropic Mn-O-Mn bond bending, which causes a significant anisotropic overlap of neighboring Mn orbitals. Due to the anisotropic double exchange interaction, it is found that the conductivity of the La2/3Sr1/3MnO3 film is enhanced when current is applied along the in-plane short crystalline axis. However, the anisotropic behavior is absent in the high temperature paramagnetic phase. Our results demonstrate anisotropic transport in the clean limit where phase separation is absent and the role of anisotropic phase percolation can be excluded.


Effects of prostaglandins on [Ca2+]i and adenylate cyclase activity in isolated porcine gastric mucous cells.
In porcine gastric mucous cells, isolated enzymatically from the fundic mucosa and enriched by counterflow centrifugation, PGE2 (1 microM) increased adenylate cyclase activity to 225% and, distinct from that documented for other species, also [Ca2+]i, measured fluorimetrically with Fura2/AM, in Ca(2+)-containing and Ca(2+)-free incubation medium to 182% and 165% of control values, respectively. PGF2 alpha, PGD2, the stable prostacyclin analogue iloprost and the thromboxane-mimetic U46619 had no significant effects on adenylate cyclase activity and [Ca2+]i. Histamine (10 microM) stimulated adenylate cyclase activity to 236% of control value, an effect which could be blocked by the H2-receptor antagonist ranitidine. However, histamine and the activators of the cAMP system forskolin and dibutyryl cAMP had no significant effect on [Ca2+]i, indicating that an activation of the adenylate cyclase/cAMP system per se does not result in an increase in [Ca2+]i. These data suggest that prostanoids stimulate adenylate cyclase activity and [Ca2+]i in gastric mucous cells via activation of EP-receptors linked to both second messenger systems.


Neuronal precursors within the adult rat subventricular zone differentiate into dopaminergic neurons after substantia nigra lesion and chromaffin cell transplant.
Neurogenesis in the adult mammalian brain continues in the subventricular zone (SVZ). Neuronal precursors from the SVZ migrate along the rostral migratory stream to replace olfactory bulb interneurons. After the destruction of the nigro-striatal pathway (SN-lesion), some SVZ precursors begin to express tyrosine hydroxylase (TH) and neuronal markers (NeuN). Grafting of chromaffin cells (CCs) into the denervated striatum increases the number of TH+ cells (SVZ TH+ cells; Arias-Carrión et al., 2004). This study examines the functional properties of these newly differentiating TH+ cells. Under whole-cell patch-clamp, most SVZ cells recorded from lesioned and grafted animals (either TH+ or TH-) were non-excitable. Nevertheless, a small percentage of SVZ TH+ cells had the electrophysiologic phenotype of mature dopaminergic neurons and showed spontaneous postsynaptic potentials. Dopamine (DA) release was measured in SVZ and striatum from both control and SN-lesioned rats. As expected, 12 weeks after SN lesion, DA release decreased drastically. Nevertheless, 8 weeks after CCs graft, release from the SVZ of SN-lesioned rats recovered, and even surpassed that from control SVZ, suggesting that newly formed SVZ TH+ cells release DA. This study shows for the first time that in response to SN-lesions and CC grafts neural precursors within the SVZ change their developmental program, by not only expressing TH, but more importantly by acquiring excitable properties of mature dopaminergic neurons. Additionally, the release of DA in a Ca(2+)-dependent manner and the attraction of synaptic afferents from neighboring neuronal networks gives further significance to the overall findings, whose potential importance is discussed.


Rapid processing of fetal skin for prenatal diagnosis by light and electron microscopy.
A method has been developed for rapid processing of fetal skin for prenatal diagnosis of hereditary skin diseases by light and electron microscopy. Fixation, dehydration, embedding, and polymerisation can be achieved in about 5 h. The quality of tissue preservation compares favourably with that produced by slower conventional techniques. This procedure may provoke a wider interest in the potential use of fetal skin biopsy in prenatal diagnosis, especially if identification of structural abnormalities is a feasible alternative to more time consuming biochemical analysis.


Relating psychological and social factors to academic performance: A longitudinal investigation of high-poverty middle school students.
We investigated the relations between middle school students' psychological factors (academic commitment and emotional control), social perceptions (family involvement and school climate), and academic performance over time. Gender differences in these relations were also examined. Based on a two-year longitudinal data set of 942 middle-school students from a high-poverty district in the United States, we found that all four factors measured in 6th grade were predictive of GPA at the end of the 7th grade above and beyond gender, race, and home intellectual materials. Among these factors, emotional control had the strongest relation with GPA, and the importance of family involvement increased over time, especially for female students. The results also revealed the indirect effects of the social factors on GPA through the psychological factors, and mostly through emotional control. These findings highlight the complex relation between the social-emotional factors and academic outcomes in early adolescence.


Course of intoxications due to concurrent ethylene glycol and ethanol ingestion.
Antidote ethanol is the basic treatment in ethylene glycol (EG) poisoning. EG ingestion is occasionally combined with ethanol. The objective was to evaluate the course of intoxications due to concurrent EG and ethanol ingestion. Data about clinical course of EG poisonings with coincidental ethanol ingestion reported to the Czech Toxicological Information Centre in the years 2000-2002 were analysed, and they were completed by data from discharge records from the hospitals and by toxicological analyses. We evaluated the clinical course of seven persons with EG and ethanol ingestion. There were six males (age 28-52 years) and one female (age 17 years). Ingested dose of EG was known in six men (mean value 517 ml, range 100-1000 ml), two of them had EG blood level measured (1.09 and 5.00 g/l) and their ethanol in blood on admission was 0.55 and 2.46% per hundred. In a woman EG blood level on admission (2.10 g/l) confirmed the ingested lethal dose. Four patients developed metabolic acidosis. Four patients had substantially increased laboratory markers of nephrotoxicity. Four patients had also mildly increased markers of hepatotoxicity. All patients were treated with the antidote ethanol. Because of high-ingested dose six patients received haemodialysis. All seven patients from our study survived. The course and outcome of EG intoxication in this group of patients was very probably positively influenced by concurrent ingestion of EG and ethanol.


[Application of mixed reality real-time navigation combined with 3D visualization in complicated hepatectomy].
Objective: To explore the application value of mixed-reality (MR) navigation combined with three-dimensional visualization technique in complicated hepatectomy. Methods: A retrospective analysis of the clinical data of fifty patients with complex liver cancer who underwent liver resection in the Department of hepatobiliary surgery of Nantong Tumor Hospital during September 2015 to October 2017 was conducted. These patients were randomly divided into control group and experimental group, including 22 cases in the experimental group, using three-dimensional visualization technique for preoperative assessment, and MR surgery intraoperative navigation technology, and 28 cases in the control group, in which the three-dimensional visualization technique and the MR navigation were not performed. The surgeons of the two groups were the same. The preoperative, intraoperative and postoperative indexes of the two groups were compared and analyzed. Results: There was no significant difference in preoperative indexes. But in the intraoperative indexes, the operation time [(82.3±10.4) min vs (96.6±22.7) min] and hepatic portal blocking time [(12.2±3.8) min VS (15.8±4.2) min] of the experimental group were significantly shorter than those of the control group, meanwhile, the amount of intraoperative bleeding [(486.4±118.5) ml vs (567.2±142.8) ml] and the volume of intraoperative blood transfusion of [(1.8±0.2) U vs (2.5±0.6) U] were significantly decreased. These differences were statistically significant. In the postoperatively, the total incidence of postoperative complications (4/22 vs 13/28) of the experimental group was lower than that of the control group, and the difference was statistically significant. Conclusion: In complicated hepatectomy, MR intraoperative navigation combined with three-dimensional visualization technique which used for preoperative assessment can significantly shorten operation time, hepatic portal blocking time, significantly reduce intraoperative blood loss and transfusion volume, and significantly reduce the incidence of postoperative total complications, which is of clinical value.


Mode of action of 5-fluorocytosine and mechanisms of resistance.
Mode of action of 5-fluorocytosine (5-FC) and mechanisms of resistance to the drug are discussed on the basis of experiments performed with Candida albicans ATCC 26790 and with 50 selected clinical isolates of C. albicans belonging to serological type A or B and representing various degrees and models of 5-FC resistance (sensitivity). Incorporation of 5-fluorouridylic acid into RNA appeared as a prerequisite to antifungal activity, although at a given incorporation rate, growth inhibition varied considerably from one strain to the other. The amino acid pool was unbalanced, and there was evidence for disturbance of protein synthesis. These dysfunctions of RNA probably account for growth inhibition and cell death, whereas up to the present, there was no proof of formation of 5-fluorodeoxyuridylic acid nor of subsequent inhibition of thymidylate synthetase. Incorporation of fluorinated pyrimidine into RNA was lower in normally sensitive type B strains than in normally sensitive ones of type A, whereas the frequency of 5-FC-resistant mutants was the same. The two serological types did not differ in the activity of cytosine permease nor in that of cytosine deaminase. Among 29 clinical isolates with 6-FC resistance (or impaired sensitivity) no instance of cytosine permease deficiency was found. Two isolates (belonging to the serological type A) were deficient in cytosine deaminase, whereas the majority was probably deficient in uridine monophosphate pyrophosphorylase or had a surplus of de novo synthesis of pyrimidines. Relative 5-FC resistance was more common than complete resistance.


Stability of oxaliplatin in infusion bags containing 5% dextrose injection.
The stability of oxaliplatin in infusion bags containing 5% dextrose injection was studied. Solutions of oxaliplatin 0.7 mg/mL were prepared in polyolefin infusion bags containing 5% dextrose injection and stored at 3-7 degrees C in a lightproof bag, at 20-24 degrees C with continuous exposure to artificial light, and at 20-24 degrees C with continuous exposure to fluorescent light in a lightproof bag. Samples were analyzed at 1, 2, 3, 4, 5, 7, 14, and 30 days and assayed in duplicate. Stability was measured using a stability-indicating high-performance liquid chromatographic method. Samples were also examined for changes in color and pH and for the presence of particulate matter. All samples retained over 90% of their initial concentration over the study period. No color changes or visible precipitation was observed, and the pH of all samples remained stable. Neither temperature nor artificial light had any significant effect on the stability of oxaliplatin. Oxaliplatin 0.7 mg/mL in infusion bags containing 5% dextrose injection was chemically stable for at least 30 days at both 3-7 degrees C and 20-24 degrees C without regard to light exposure.


Frequency-domain multiscale quantum mechanics/electromagnetics simulation method.
A frequency-domain quantum mechanics and electromagnetics (QM∕EM) method is developed. Compared with the time-domain QM/EM method [Meng et al., J. Chem. Theory Comput. 8, 1190-1199 (2012)], the newly developed frequency-domain QM∕EM method could effectively capture the dynamic properties of electronic devices over a broader range of operating frequencies. The system is divided into QM and EM regions and solved in a self-consistent manner via updating the boundary conditions at the QM and EM interface. The calculated potential distributions and current densities at the interface are taken as the boundary conditions for the QM and EM calculations, respectively, which facilitate the information exchange between the QM and EM calculations and ensure that the potential, charge, and current distributions are continuous across the QM/EM interface. Via Fourier transformation, the dynamic admittance calculated from the time-domain and frequency-domain QM/EM methods is compared for a carbon nanotube based molecular device.


The Effect of Panax ginseng on Genitourinary Syndrome in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Menopause and estrogen deprivation cause a rise in the number of urogenital tract complaints. This study was conducted to assess the effectiveness of ginseng on genitourinary syndrome. This randomized trial was conducted on 60 postmenopausal women with genitourinary syndrome. The participants were randomly allocated to ginseng and placebo groups twice daily for 4 weeks. Vaginal maturation index and vaginal pH were evaluated before and 4 weeks after intervention as the primary outcomes. Also, the atrophic vaginitis and incontinence questionnaires were completed before and after intervention as the secondary outcomes. The safety of intervention was assessed by the side effects checklist. No significant differences were observed between the 2 groups in objective symptoms after the intervention, but the difference was statistically significant (p < 0.001) in terms of subjective symptoms of atrophic vaginitis. One case of insomnia and palpitation and 2 cases of hot flashes were reported in the intervention group, and 1 case of gastric discomfort and change in urine appearance was reported in the placebo group. Ginseng only improved the patient-assessed symptoms and had no significant effect on the clinician-assessed outcomes. Further studies are required to determine the precise pharmacological mechanisms of ginseng on genitourinary syndrome.


Retinitis pigmentosa and hypogammaglobulinemia.
This report describes a family demonstrating an unusual association of retinitis pigmentosa and hypogammaglobulinemia. The proband in this family suffered from another rare illness, ie, Sertoli cell only syndrome. The incidence of retinitis pigmentosa is 1 in 5,000 and that of common variable immunodeficiency state is 1 in 100,000, making a chance association of these illnesses very unlikely.


Absolute lymphocyte count as a predictor of Pneumocystis pneumonia in patients previously unknown to have HIV.
This is a retrospective review of patients admitted to an inner city community hospital with community-acquired pneumonia who were ultimately diagnosed with AIDS and Pneumocystis. Absolute lymphocyte count in our hospital is available immediately. In contrast, it can take 48 hours or longer to obtain more specific CD-4 counts and AIDS enzyme-linked immunosorbent assay (ELISA) serology. The association of lymphopenia with ultimate diagnosis of AIDS and Pneumocystis supports immediate empiric treatment for pneumocystis carinii pneumonia (PCP) in our highly HIV prevalent hospital.


The Peripubertal Decline in Makorin Ring Finger Protein 3 Expression is Independent of Leptin Action.
A critical body weight is necessary for pubertal development, an effect mediated in part by leptin. The potential regulation by leptin of Makorin Ring Finger Protein 3 (MKRN3), in which loss-of-function mutations are the most common genetic cause of central precocious puberty, has not been previously explored. In mice, expression of Mkrn3 in the hypothalamic arcuate nucleus is high early in life and declines before the onset of puberty. Therefore, we aimed to explore if leptin contributes to the decrease in hypothalamic Mkrn3 mRNA levels observed in mice during pubertal development. We first used a leptin-deficient (ob/ob) mouse model. Mkrn3 mRNA levels in the mediobasal hypothalamus (MBH), which includes the arcuate nucleus, and in the preoptic area (POA), both showed a significant decrease with age from postnatal day (PND) 12 to PND30 in ob/ob mice in both males and females, similar to that observed in wild-type mice. To further explore the effects of leptin on Mkrn3 expression, we exposed prepubertal wild-type mice to high levels of leptin from age PND9-12, which did not result in any significant difference in Mkrn3 expression levels in either the MBH or POA. In summary, regulation of Mkrn3 expression by leptin was not observed in either the MBH or the POA, 2 hypothalamic sites important for pubertal maturation. These data suggest that the decline in Mkrn3 at the onset of puberty may occur independently of leptin and support our hypothesis that MKRN3 is a bona fide controller of puberty initiation.


Anti-Mullerian hormone in the diagnosis of polycystic ovary syndrome: can morphologic description be replaced?
Can anti-Müllerian hormone (AMH) level replace the morphologic description in the diagnosis of polycystic ovary syndrome (PCOS) and what is the relationship between AMH and different diagnostic criteria of PCOS? AMH may be a good substitute for polycystic ovarian morphology (PCOM) in diagnosing PCOS. AMH has been suggested as an alternative to antral follicle count (AFC) in diagnosing PCOS. Cut-off values for AMH studied so far show an acceptable specificity but a rather poor sensitivity, leaving up to one-third of PCOS women undiagnosed. We used data from a cross-sectional, case-control study on women with prior preterm birth and their controls, i.e. women with prior full-term birth. Among 262 women, 56 met the Rotterdam criteria (PCOS-R) and 44 the Androgen Excess-PCOS Society (PCOS-AES) criteria of PCOS. Fasting blood samples were collected, a transvaginal ultrasound investigation and a clinical examination were performed. PCOS-R and PCOS-AES were re-diagnosed by replacing PCOM with AMH. Main outcome measures were the prevalence of PCOS, PCOM, hirsutism, oligoamenorrhoea and serum levels of AMH and androgens. When replacing PCOM with AMH, the specificity and sensitivity for identifying PCOS were 97.1 and 94.6% according to the PCOS-R criteria and 97.2 and 95.5% according to the PCOS-AES criteria, respectively, at an AMH cut-off value of 20 pmol/l. The results need to be confirmed when international standards and methods for AMH measurements are established. AMH may be a good substitute for PCOM in diagnosing PCOS. This study was financed by the Cooperative of Central Norway Regional Health Authority and Norwegian University of Science and Technology. The authors have no interests to disclose. This study is registered at www.clinicaltrials.gov as NCT01355536.