Bloch Surface Wave-Coupled Emission at Ultra-Violet Wavelengths.
The interaction of fluorophores with nearby metallic structures is now an active area of research. Dielectric photonic structures offer some advantages over plasmonic structures, namely small energy losses and less quenching. We describe a dielectric one-dimensional photonic crystal (1DPC), which supports Bloch surface waves (BSWs) from 280 to 440 nm. This BSW structure is a quartz slide coated with alternating layers of SiO2 and Si3N4. We show that this structure displays BSWs and that the near-UV fluorophore, 2-aminopurine (2-AP), on the top surface of the structure couples with the BSWs. Fluorophores do not have to be inside the structure for coupling and show a narrow angular distribution, with an angular separation of wavelengths. The Bloch wave-coupled emission (BWCE) radiates through the dielectric layer. These BSW structures, with useful wavelength range for detection of intrinsic protein and cofactor fluorescence, provide opportunities for novel optical configurations for bioassays with surface-localized biomolecules and for optical imaging using the coupled emission.


Update on distance and velocity requirements for community ambulation.
The purposes of this study were to provide an update to the ambulatory distance requirements for community ambulation and to update gait speed performance and requirements at intersections. Distances were measured at 9 types of sites using a rolling measuring device in accordance with the protocol set forth by Lerner-Frankiel and associates. The 9 types of sites were supermarkets, drug stores, banks, department stores, post offices, medical offices, superstores, club warehouses, and hardware stores. Gait speed allotted by crosswalk signals as well as the gait speeds of individuals through crosswalks were recorded. Qualitative observations of the pedestrians' age (older - 65 years; younger < 65 years) and sex were also noted. Distances were measured at 141 different establishments. The shortest mean distance requirement was found in the medical offices at 65.82 (32.28) m. Club warehouses had the longest mean distance requirement at 676.82 (159.36) m. The mean gait speed used by the pedestrians (N = 139) was 1.32 (0.31) m/s while the mean speed necessary as set by the crosswalk signals was 0.49 (0.20) m/s. All of the individuals observed were able to cross the street within the allotted time and with adequate speed. The gait speeds met the normative data established for age and sex as well as data reported for slower older adults and some with incomplete spinal cord injury. Distance requirements for full community ambulation may need to be increased to 600 m or more. Gait speed requirements at crosswalks in the communities measured are set to accommodate the gait speed capabilities of older pedestrians who attempt crossing at controlled intersections.


The Gene Variants of Maternal/Fetal Renin-Angiotensin System in Preeclampsia: A Hybrid Case-Parent/Mother-Control Study.
Preeclampsia (PE) is a common pregnancy-related complication, and polymorphisms in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) are believed to contribute to PE development. We implemented a hybrid study to investigate the influence of maternal and fetal ACE I/D, ACE G2350A, AGT M235T, AGT T174M, and AT1R A1166C polymorphisms on PE in Han Chinese women. Polymorphisms were genotyped in 1,488 subjects (256 patients experiencing PE, along with their fetuses and partners, and 360 normotensive controls with their fetuses). Transmission disequilibrium tests revealed that ACE I/D (P = 0.041), ACE G2350A (P = 0.035), and AT1R A1166C (P = 0.018) were associated with maternal PE. The log-linear analyses revealed that mothers whose offspring carried the MM genotype of AGT M235T had a higher risk of PE (OR = 1.54, P = 0.010), whereas mothers whose offspring carried the II genotype of ACE I/D or the GG genotype of ACE G2350A had a reduced risk (OR = 0.58, P = 0.039; OR = 0.47, P = 0.045, respectively). Our findings demonstrate that fetal ACE I/D, ACE G2350A, AGT M235T, and AT1R A1166C polymorphisms may play significant roles in PE development among pregnant Han Chinese women.


The role of maternal nutrition, metabolic function and the placenta in developmental programming of renal dysfunction.
The intrauterine environment is critical for the development of the foetus. Barker and colleagues were the first to identify that adverse perturbations during foetal development are associated with an increased risk of developing diseases in adulthood, including cardiorenal disease. Specifically for the kidney, perturbations in utero can lead to nephron deficits and renal dysfunction by a number of mechanisms. Altered programming of nephron number is associated with an increased risk of developing kidney disease via glomerular hypertrophy and reduced vasodilative capacity of the renal blood vessels; both of which would contribute to hypertension in adulthood, with males being more susceptible to disease outcomes. Additionally, alterations in the renin-angiotensin system (RAS) such as an upregulation or downregulation of specific receptors, depending on the nature of the insult, have also been implicated in the development of renal dysfunction. Sex-specific differences in the expression of the RAS during late gestation and in the early postnatal environment have also been identified. Extensive research has demonstrated that both uteroplacental insufficiency and maternal malnutrition alter renal development in utero. Equally, exposure to maternal diabetes and maternal obesity during development are also associated with an increased risk of developing renal disease, however, the mechanism behind this association is poorly understood. Therefore, identifying the link between an adverse intrauterine environment and the programmed kidney disease risk in adulthood may facilitate the development of strategies to alleviate the epidemics of cardiorenal disease worldwide, in addition to understanding why males are more susceptible to adult-onset cardiovascular diseases.


Mention effect in information diffusion on a micro-blogging network.
Micro-blogging systems have become one of the most important ways for information sharing. Network structure and users' interactions such as forwarding behaviors have aroused considerable research attention, while mention, as a key feature in micro-blogging platforms which can improve the visibility of a message and direct it to a particular user beyond the underlying social structure, is seldom studied in previous works. In this paper, we empirically study the mention effect in information diffusion, using the dataset from a population-scale social media website. We find that users with high number of followers would receive much more mentions than others. We further investigate the effect of mention in information diffusion by examining the response probability with respect to the number of mentions in a message and observe a saturation at around 5 mentions. Furthermore, we find that the response probability is the highest when a reciprocal followship exists between users, and one is more likely to receive a target user's response if they have similar social status. To illustrate these findings, we propose the response prediction task and formulate it as a binary classification problem. Extensive evaluation demonstrates the effectiveness of discovered factors. Our results have consequences for the understanding of human dynamics on the social network, and potential implications for viral marketing and public opinion monitoring.


Enantioselective Synthesis of Polysubstituted Spiro-nitroprolinates Mediated by a (R,R)-Me-DuPhos·AgF-Catalyzed 1,3-Dipolar Cycloaddition.
The synthesis of constrained spirocycles is achieved effectively by means of 1,3-dipolar cyclodditions employing α-imino γ-lactones as azomethine ylide precursors and nitroalkenes as dipolarophiles. The complex formed by (R,R)-Me-DuPhos 18 and AgF is the most efficient bifunctional catalyst. Final spiro-nitroprolinates cycloadducts are obtained in good to moderate yields and both high diastereo- and enantioselectivities. Density functional theory (DFT) calculations supported the expected absolute configuration as well as other stereochemical parameters.


Gold(iii)-catalyzed azide-yne cyclization/O-H insertion cascade reaction for the expeditious construction of 3-alkoxy-4-quinolinone frameworks.
A gold-catalyzed 6-endo-dig azide-yne cyclization/O-H insertion cascade reaction of azide-tethered alkynes with alcohols has been developed, and it provides an expeditious access to 3-alkoxy-4-quinoline derivatives in good to high yields under mild and neutral reaction conditions with broad substrate generality. The utility of this method is emphasized by a scalable experiment and concise total synthesis of a bioactive natural product Leiokinine A, and other bioactive quinoline analogs.


The beginnings of long QT syndrome.
The purpose of this study is to update the perinatal cardiologist and obstetrical care provider on the presentation and management of the fetus with long QT syndrome (LQTS). LQTS is a known cause of sudden death in childhood, adolescence and young adulthood that presents during fetal life, but is often not recognized. Torsades de pointes (TdP) ±2° atrioventricular block (AVB) are not always attributed to LQTS, although the most common LQTS rhythm, a fetal heart rate of less than third percentile for gestational age (GA), is not recognized as abnormal because it does not meet the standard obstetrical criteria for bradycardia. Early recognition and appropriate treatment can be life saving for the fetus and unsuspecting LQTS family members. Fetal rhythm phenotype and postnatal QTc can predict postnatal rhythm and suggest genotype: bradycardic fetuses usually have KCNQ1 mutation, while those with TdP and/or a postnatal QTc more than 500 ms have SCN5A, KCNH2 or uncharacterized mutations. The fetus with repeated heart rates of less than third percentile of GA and those with TdP ±2° AVB are likely to manifest the same rhythm after birth and have an LQTS mutation.


Epidemiological verification of the mechanism of occurrence of atypical L-type bovine spongiform encephalopathy.
Since 2004, a novel bovine spongiform encephalopathy (BSE), distinct from the conventional 'classical BSE' (C-BSE), has been reported as an atypical BSE. Atypical BSE is detected mostly in aged cattle, and it is suggested that atypical BSE may occur spontaneously. Relaxation of the relevant countermeasures such as feed ban, which prevents the use of bovine meat-and-bone meal as feed, has been discussed in recent years owing to the decrease in C-BSE cases. If atypical BSE occurs spontaneously without exposure to an agent called abnormal prion protein (PrPSc ), complete removal of these measures will be difficult. In this study, we verified the possibility that L-BSE, which is a subtype of atypical BSE, occurs spontaneously. We first hypothesized that L-BSE occurs only through the process of infection via oral exposure. If the hypothesis was true, the infection of L-BSE would be mostly limited to calves under 1 year of age due to their high susceptibility, and the feed ban would effectively reduce the number of infected calves by birth cohort. Thus, we created a mathematical model to estimate the number of infected calves by birth cohort and compared the effectiveness of the feed ban on C-BSE and L-BSE. The number of tested animals and detected cases in nine European countries were used for this analysis. Our results showed that the estimated number of infected calves in the birth cohort indicated that feed ban was less effective on L-BSE. This result supports the alternative hypothesis that at least a part of the L-BSE can occur without infection via oral exposure. Our results suggest that the complete abolition of countermeasures, such as feed ban, should be discussed carefully. As for the occurrence mechanism, although there remains uncertainty to reach conclusions, it is reasonable to assume that L-BSE can occur spontaneously at present.


Tetramesityldisilene, a stable compound containing a silicon-silicon double bond.
Irradiation of 2,2-bis(2,4,6-trimethylphenyl)hexamethyltrisilane in hydrocarbon solution produces tetramesityldisilene, which can be isolated as a yellow-orange solid stable to room temperature and above in the absence of air. Like the olefins of carbon chemistry, tetramesityldisilene undergoes addition reactions across the silicon-silicon double bond.


Stability of Spironolactone Oral Suspension in PCCA Base, SuspendIt.
Spironolactone (Aldactone) is a potassium-sparing diuretic used to treat hypertension and heart failure and may also be used to treat edema resulting from kidney disease, low potassium levels, or excess aldosterone. No commercial liquid dosage form of spironolactone exists. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide an alternative option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of spironolactone in the PCCA base SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. It thickens upon standing to minimize settling of any insoluble drug particles and becomes fluid upon shaking to allow convenient pouring during administration to the patient. A robust stability-indicating highperformance liquid chromatographic assay for the determination of spironolactone in PCCA base SuspendIt was developed and validated. This assay was used to determine the chemical stability of the drug in SuspendIt. Samples were prepared and stored under three different temperature conditions (5°C, 25°C, 40°C) and assayed using the high-performance liquid chromatographic assay at pre-determined intervals over an extended period of time as follows: 0, 7, 14, 29, 46, 60, 90, 120, and 180 days at each designated temperature. Physical data such as pH, viscosity, and appearance were also monitored. The study showed that drug concentration did not go below 90% of the label claim (initial drug concentration) at all three temperatures studied. Viscosity and pH values also did not change significantly. This study demonstrates that spironolactone is physically and chemically stable in SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for spironolactone in a liquid dosage form, with an extended beyond-use date to meet patient needs.


Neuronal polarity and trafficking.
Among the most morphologically complex cells, neurons are masters of membrane specialization. Nowhere is this more striking than in the division of cellular labor between the axon and the dendrites. In morphology, signaling properties, cytoskeletal organization, and physiological function, axons and dendrites (or more properly, the somatodendritic compartment) are radically different. Such polarization of neurons into domains specialized for either receiving (dendrites) or transmitting (axons) cellular signals provides the underpinning for all neural circuitry. The initial specification of axonal and dendritic identity occurs early in neuronal life, persists for decades, and is manifested by the presence of very different sets of cell surface proteins. Yet, how neuronal polarity is established, how distinct axonal and somatodendritic domains are maintained, and how integral membrane proteins are directed to dendrites or accumulate in axons remain enduring and formidable questions in neuronal cell biology.


Nanosponges - a completely new nano-horizon: pharmaceutical applications and recent advances.
In recent years, nanosponges (NS) have gained tremendous impetus in drug delivery through nanotechnology. Nanosponges are capable of providing solutions for several formulation related problems. Through this review, scientists working in the field of nanotechnology can have an insight into the techniques of preparation, characterization and applications of NS. Owing to their small size and porous nature they can bind poorly-soluble drugs within their matrix and improve their bioavailability. They can be crafted for targeting drugs to specific sites, prevent drug and protein degradation and prolong drug release in a controlled manner. This review attempts to elaborate different schemes of synthesis of NS and their characterization. Factors affecting drug loading and release have been enumerated. Due to their advantages, NS have not only been explored for their pharmaceutical applications but also have large popularity in allied sciences, especially in water purification.


First Report of Stemphylium lycopersici Causing Leaf spot on Sedum plumbizincicola in Hunan Province of China.
Sedum plumbizincicola is a perennial succulent herb that can hyperaccumulate high concentrations of cadmium and zinc (Liu et al. 2017). In October 2021, a leaf spot disease occurred on S. plumbizincicola seedlings in a nursery in Changsha (28°13' N; 112°56'E), the Hunan Province of China. Almost 30% of the nearly 1 million seedlings were infected. Symptoms initially appeared as small brown spots on the leaf surface or edges, gradually enlarged, becoming oval, and bearing chlorotic lesions with dark brown borders. Eventually, the center of the lesions became sunken and then fell off. Eight symptomatic plant samples were collected by five-point sampling method (Zheng et al. 2018). Small pieces of 5×5 mm were excised from the lesion margins, sterilized with 70% ethanol for 10 s, 0.1% HgCl2 for 40 s, rinsed with sterile distilled water three times, and then cultured on potato dextrose agar (PDA) at 26 °C for 5 days in the dark. Fungal colonies showing similar morphology were observed from all the isolated samples and, in total, eight fungal strains were obtained. On PDA, fungal colonies were initially white, and later become light gray. After cultured on V8 juice agar (V8A, each litre of medium contains 200 mL of V8 juice, 3 g of CaCO3 and 15 g of agarose) for 14 days (Hyowon et al. 2016), conidia of a representative isolate SY-1 were produced, which were oblong, muriform, with blunt ends and conical apex, pale to light brown, and constricted at the 1 to 3 major transverse septa, 38.34-46.68 μm×11.67-18.34 μm (n=50). These morphological characteristics were consistent with that of Stemphylium lycopersici (Nasehi et al. 2016). The internal transcribed spacer (ITS) region of rDNA and the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene of representative isolates SY-1 to SY-3 were amplified and sequenced using the primer pairs ITS4/ITS5 and gpd1/gpd2 as described previously (Woudenberg et al. 2017). BLASTn analysis showed that ITS sequences of isolates SY-1, SY-2 and SY-3 (accession nos. OP317641, OQ852042 and OQ852043) had more than 99% identity with Stemphylium sp, while GAPDH sequences (OP331223, OQ858620 and OQ858621) had 100% identity with S. lycopersici KR911813 (Sun et al. 2016). A concatenated ITS-GAPDH phylogenetic tree grouped our isolates within the S. lycopersici clade. For the pathogenicity test, one-month-old potted S. plumbizincicola seedlings were inoculated with conidia suspension (105 conidia/ml), which was induced on V8A. Four sites of each leaf of the potted S. plumbizincicola plants were dropped with a conidia suspension of strain SY-1, with 10 μL per site. Leaves treated with sterile water were served as controls. All of the inoculated seedlings were placed in a growth chamber at 26°C with a photoperiod of 12 h. The pathogenicity tests were repeated twice, with each had three replicative plants. After 7 days, all the inoculated leaves developed brown spots resembling those observed in the nursery, whereas the control plants remained symptomless. Stemphylium lycopersici was specifically re-isolated and identified by morphological and molecular methods (accession nos. OQ852045 for ITS and OQ858622 for GAPDH, respectively), thus fulfilling Koch's postulates. To our knowledge, this is the first report of S. lycopersici causing leaf spot on S. plumbizincicola in China. Since S. plumbizincicola played an important role and widely planted for heavy metal pollution treatment (Jiang et al. 2010), and this disease might seriously influence the S. plumbizincicola seedling breeding, identification of the pathogen might provide a foundation for the diagnosis and control of the disease.


Associations between childhood polyvictimization, intimate partner violence victimization and substance use among college students.
Objectives: Intimate partner violence (IPV) is associated with an elevated risk of substance use, but few studies have simultaneously examined other aspects of victimization history that may contribute to substance use. The current study examined the direct and moderating effects of childhood polyvictimization (i.e., multiple experiences of violence victimization before age 18) on the association between IPV subtypes (physical, sexual, psychological, and injury) and alcohol/drug use. Methods: A sample of 256 college students ages 18-25 (72% female, 68% white) completed a survey assessing past-year IPV, childhood polyvictimization, and past three-month substance use. Results: There were no direct or joint associations between IPV, childhood polyvictimization, and alcohol use. There were direct associations between psychological IPV, childhood polyvictimization, and drug use. No other forms of IPV were significantly associated with drug use. Conclusions: Results highlight unique direct associations between violence victimization and drug use risk compared to alcohol use risk in this context.


Serum urate, metabolic syndrome, and cardiovascular risk factors. A population-based study.
We studied the associations between serum urate levels (determined in 503 subjects from a population of 1,344 subjects living in northern Madrid) and both the metabolic syndrome (MS) (defined by the Adult Treatment Panel III criteria) and C-reactive protein (CRP, determined in 382 subjects). MS was diagnosed in 25% (95%CI, 21-28%) and was associated with hyperuricemia (p<0.001). There was a graded increase in serum urate levels with increasing number of MS components. Urate concentrations significantly correlated with waist circumference (r=0,455, p<0.01). Serum urate was not independently associated with CRP levels. This study shows that serum urate levels are associated with the presence of MS and each of its features.


Supramolecular Guest-Host Interactions for the Preparation of Biomedical Materials.
Supramolecular chemistry has emerged as an important technique for the formation of biomaterials, including nano- and microparticles and hydrogels. One specific class of supramolecular chemistry is the direct association of guest-host pairs, which involves host macrocycles such as cyclodextrins and cucurbit[n]urils and a wide range of guest molecules, where association is typically driven by molecule size and hydrophobicity. These systems are of particular interest in the biomedical field due to their dynamic nature, chemical diversity, relative ease of synthesis, and ability to interact with biological or synthetic molecules. In this review, we discuss aspects of polymeric material assembly mediated by guest-host interactions, including the fundamentals of assembly into functional biomedical materials. Additionally, applications of biomaterials that utilize guest-host interactions are discussed with a focus on injectable material formulations, the sequestration and delivery of encapsulated cargo (i.e., drugs, biomolecules), and the investigation of cell-material interactions (i.e., adhesion, differentiation, and delivery). While methodologies for guest-host mediated assembly and biological interaction have rapidly evolved in recent years, they remain far from realizing their full potential in the biomaterials field.


Moving Closer to the 2020 BSN-Prepared Workforce Goal.
: One of the recommendations of the landmark Future of Nursing: Leading Change, Advancing Health report was to increase the proportion of nurses with a bachelor of science in nursing or higher degree to 80% by 2020. In 2012, the American Organization of Nurse Executives was selected by the Robert Wood Johnson Foundation as the National Program Office for a new initiative-the Academic Progression in Nursing (APIN) program-with the goal of identifying and developing the most promising strategies for creating a more highly educated nursing workforce. This article discusses the findings of APIN's four-year project.


Intrathecal Baclofen Therapy for the Treatment of Spasticity in Sjögren-Larsson Syndrome.
Intrathecal baclofen therapy is widely accepted as a treatment option for patients with severe spasticity. The current treatment of spasticity in patients with Sjögren-Larsson syndrome is largely symptomatic, given that no effective causal therapy treatments are available. We report the outcome of 2 patients with Sjögren-Larsson syndrome who had pump implantation for intrathecal baclofen. We observed a positive response, with a decrease of spasticity, reflecting in the Modified Ashworth Scale, and parents and caregivers observed a functional improvement in both patients. One patient experienced skin irritation 15 months after surgery, necessitating pump repositioning. No infection occurred. Our report shows that intrathecal baclofen therapy can have a positive therapeutic effect on spasticity in patients with Sjögren-Larsson syndrome, and therefore may be a promising addition to current treatments.


Growing Clinical and Academic Nursing Leaders: Building the Pipeline.
Nursing faces a crisis because there exists a dearth of qualified nurse academicians and administrators willing to step up to high-level leadership positions such as deanships and chief nursing operators. This article critically appraises the available literature regarding succession planning in the nursing profession and offers pragmatic suggestions to the profession to engage in succession planning in a deliberate and thoughtful manner.


CT findings associated with survival in chronic hypersensitivity pneumonitis.
To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. • A substantial proportion of subjects with chronic HP have a UIP-like pattern. • A UIP pattern in HP may be potentiated by smoking. • A diagnosis of HP should not be excluded based solely on CT appearance. • CT fibrosis and increased PA/aorta ratio signal worse survival.


[Lymphocyte depletion after irradiation of the chest region dependent on irradiation technics].
In a prospective alternating study, the mediastinum of patients with bronchial carcinomas was preoperatively irradiated with 2000 cGy in ten fractions for an isodose of 80% by Co-60 stationary field or pendulum therapy. The leucocyte and lymphocyte blood count was determined every day. It was found out that the lymphocyte depression was significantly higher after pendulum therapy than after stationary field therapy. This is explained by the fact that the lymphocyte depression is caused rather by the irradiation of lymphocytes in the blood stream than by the irradiation of bone marrow.


Unique Location and Origin of a Ganglion Cyst.
Ganglion cysts usually occur around the wrist. Occasionally, they can also occur around the shoulder in the spinoglenoid and suprascapular notches. Rarely they can be found on the long head of biceps as it traverses the glenohumeral joint. Such lesions are usually diagnosed on MRI and might need minor surgery. We present the case of a young athlete with a rare location of ganglion cyst, successfully diagnosed and managed non-invasively by using sonography. This represents a time and cost-conscious approach as compared to traditional methods.


Cyclooxygenase-2 inhibition protects cultured cerebellar granule neurons from glutamate-mediated cell death.
Primary insults to the brain can initiate glutamate release that may result in excitotoxicity followed by neuronal cell death. This secondary process is mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA receptors in vivo and requires new gene expression. Neuronal cyclooxygenase-2 (COX2) expression is upregulated following brain insults, via glutamatergic and inflammatory mechanisms. The products of COX2 are bioactive prostanoids and reactive oxygen species that may play a role in neuronal survival. This study explores the role of neuronal COX2 in glutamate excitotoxicity using cultured cerebellar granule neurons (day 8 in vitro). Treatment with excitotoxic concentrations of glutamate or kainate transiently induced COX2 mRNA (two- and threefold at 6 h, respectively, p < 0.05, Dunnett) and prostaglandin production (five- and sixfold at 30 min, respectively, p < 0.05, Dunnett). COX2 induction peaked at toxic concentrations of these excitatory amino acids. Surprisingly, NMDA, L-quisqualate, and trans-ACPD did not induce COX2 mRNA at any concentration tested. The glutamate receptor antagonist NBQX (5 microM, AMPA/kainate receptor) completely inhibited kainate-induced COX2 mRNA and partially inhibited glutamate-induced COX2 (p < 0.05, Dunnett). Other glutamate receptor antagonists, such as MK-801 (1 microM, NMDA receptor) or MCPG (500 microM, class 1 metabotropic receptors), partially attenuated glutamate-induced COX2 mRNA. These antagonists all reduced steady-state COX2 mRNA (p < 0.05, Dunnett). To determine whether COX2 might be an effector of excitotoxic cell death, cerebellar granule cells were pretreated (24 h) with the COX2-specific enzyme inhibitor, DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2((5)H)-furanone) prior to glutamate challenge. DFU (1 to 1000 nM) completely protected cultured neurons from glutamate-mediated neurotoxicity. Approximately 50% protection from NMDA-mediated neurotoxicity, and no protection from kainate-mediated neurotoxicity was observed. Therefore, glutamate-mediated COX2 induction contributes to excitotoxic neuronal death. These results suggest that glutamate, NMDA, and kainate neurotoxicity involve distinct excitotoxic pathways, and that the glutamate and NMDA pathways may intersect at the level of COX2.


Atom probe tomographic assessment of the distribution of germanium atoms implanted in a silicon matrix through nano-apertures.
Ion implantation through nanometer-scale apertures (nano-apertures) is a promising method to precisely position ions in silicon matrices, which is a requirement for next generation electronic and quantum computing devices. This paper reports the application of atom probe tomography (APT) to investigate the three-dimensional distribution of germanium atoms in silicon after implantation through nano-aperture of 10 nm in diameter, for evaluation of the amount and spatial distribution of implanted dopants. The experimental results obtained by APT are consistent with a simple simulation with consideration of several effects during lithography and ion implantation, such as channeling and resist flow.


The place of IVF in infertility care.
In vitro fertilization has become standard treatment for infertility without the benefit of thorough evaluation. Today, the effectiveness of IVF is the subject of ongoing debate, the medical and non-medical risks of treatment are not adequately understood, and there is great concern about the true costs of care both for individuals and society. Added to this debate are ethical dilemmas which have changed the way we think about reproductive rights, the family, parenthood, intergenerational responsibilities, and the legal status of children and embryos. In order to address these issues, the World Health Organization Regional Office for Europe held a meeting in June 1990 on the Place of In Vitro Fertilization in Infertility Care. The recommendations from the meeting are presented.


A case of Whipple's disease complicated by fatal hepatitis.
Whipple's disease was diagnosed in a 42-year-old woman by the histological examination of a mesenteric lymph node taken at laparotomy, and the electron microscopic examination of a peroral intestinal biopsy specimen. She responded well to tetracycline therapy, but succumbed to fatal hepatitis ten weeks after the diagnosis of Whipple's disease


Visual complications following irradiation for pituitary adenomas and craniopharyngiomas.
Of 55 patients with pituitary adenomas or craniopharyngiomas treated with irradiation, a retrospective study revealed that 5 sustained a visual loss compatible with radiation damage to the optic nerve. No patient who received less than 250 rads/day fractions showed such visual loss. Within the range of total dosages used in this series, total dose was not an important determinant of this complication. The time to occurrence of visual disturbance ranged from 5 to 34 months following therapy.


In vivo significance of the G2 restriction point.
Loss of activity of the retinoblastoma pathway is a common event in human cancer. Mouse models have revealed that tumorigenesis by loss of Rb was accelerated by concomitant loss of the cell cycle inhibitor p27KIP1. This has been attributed to reduced apoptosis and weakening of the G1 checkpoint. However, the role of p27KIP1 in a recently identified G2 restriction point may offer an alternative explanation for this synergy. Here, we have investigated the significance of the G2 restriction point in Rb-deficient pituitaries. We show that Rb loss in the pituitary gland activated the G2 restriction point, as evidenced by the appearance of cyclin B1-p27KIP1 complexes. Somewhat unexpectedly, these complexes remained present in Rb-deficient tumors. These results indicate that the G2 restriction point does operate in vivo. However, in the pituitary gland, this mechanism seems to retard rather than to prevent tumor growth.


Neoadjuvant photodynamic therapy augments immediate and prolonged oxaliplatin efficacy in metastatic pancreatic cancer organoids.
Effective treatment of advanced metastatic disease remains the primary challenge in the management of inoperable pancreatic cancer. Current therapies such as oxaliplatin (OxPt)-based chemotherapy regimens (FOLFIRINOX) provide modest short-term survival improvements, yet with significant toxicity. Photodynamic therapy (PDT), a light-activated cancer therapy, demonstrated clinical promise for pancreatic cancer treatment and enhances conventional chemotherapies with non-overlapping toxicities. This study investigates the capacity of neoadjuvant PDT using a clinically-approved photosensitizer, benzoporphyrin derivative (BPD, verteporfin), to enhance OxPt efficacy in metastatic pancreatic cancer. Treatment effects were evaluated in organotypic three-dimensional (3D) cultures, clinically representative models that bridge the gap between conventional cell cultures and in vivo models. The temporally-spaced, multiparametric analyses demonstrated a superior efficacy for combined PDT+OxPt compared to each monotherapy alone, which was recapitulated on different organotypic pancreatic cancer cultures. The therapeutic benefit of neoadjuvant PDT to OxPt chemotherapy materialized in a time-dependent manner, reducing residual viable tissue and tumor viability in a manner not achievable with OxPt or PDT alone. These findings emphasize the need for intelligent combination therapies and relevant models to evaluate the temporal kinetics of interactions between mechanistically-distinct treatments and highlight the promise of PDT as a neoadjuvant treatment for disseminated pancreatic cancer.


Chimeric Superficial Circumflex Iliac Perforator Flap Including External Oblique Fascia: A Refinement of Conventional Harvesting.
The superficial circumflex iliac perforator (SCIP) flap is one of the most suitable flaps to cover distal extremity defects due to its lack of bulkiness and donor site concealment. However, it is less popular than other perforator flaps due to its anatomical variations, short pedicle length, and small caliber vessels. We describe a novel design for the SCIP flap, consisting of a chimeric flap with a piece of the external oblique muscle fascia. The purpose of this design is to cover and protect the vascular anastomosis in distal lower limb defects where recipient vessels are superficial and skin coverage is poor. In addition, lengthening the pedicle with this design makes the flap more versatile. The addition of a cuff of fascia in harvesting of the SCIP flap lengthens the pedicle, allowing easier insetting of the skin paddle and providing complete protection and coverage of the vessels. This procedure allows greater versatility in inset of the skin paddle and is particularly suitable in cases where recipient vessels are superficial or when skin coverage is poor.


The association between job strain and atrial fibrillation in Swedish men.
The purpose of this study was to investigate whether psychosocial stress defined as high strain based on the job demand-control model increases risk for atrial fibrillation. The present study comprised 6035 men born between 1915 and 1925 and free from previous coronary heart disease, atrial fibrillation and stroke at baseline (1974-1977). Work-related psychosocial stress was measured using a job-exposure matrix for the job demand-control model based on occupation at baseline. The participants were followed from baseline examination until death, hospital discharge or 75 years of age, using the Swedish national register on cause of death and the Swedish hospital discharge register for any registration for atrial fibrillation, resulting in the identification of 436 cases. Data were analysed with Cox regression models with atrial fibrillation as the outcome using high strain as the explanatory variable adjusted for age, smoking, body mass index, hypertension, diabetes and socioeconomic status. There was an increased risk for atrial fibrillation in relation to high strain (HR 1.32, 95% CI 1.003 to 1.75). When the four categories of the job-strain model were included and low strain was used as reference, the risk for high strain decreased (HR 1.23, 95% CI 0.84 to 1.82). Exposure to occupational psychosocial stress defined as high strain may be associated with increased risk for atrial fibrillation. The observed increase in risk is small and residual confounding may also be present.


During development, 17alpha-estradiol is a potent estrogen and carcinogen.
Neonatal administration of estradiol-17beta (E2-17beta) increases the nuclear DNA content in the mouse reproductive tract. Similar responses have been demonstrated for synthetic estrogens such as diethylstilbestrol. One of the questions raised regarding environmental estrogens such as organochlorines is whether they are potent enough to result in abnormal changes such as those demonstrated by both natural and synthetic estrogens. To test this hypothesis, female BALB/c mice were treated neonatally (days 1-5) with either E2-17beta or estradiol-17alpha (E2-17alpha), an inactive stereoisomer in adult reproductive tissues. We also proposed whether neonatal administration of (E2-17alpha) was tumorigenic and whether the effects were age dependent. To answer these questions, one set each of 10 day-old treated and control mice received short-term secondary administration of E2-17beta, E2-17alpha, or cholesterol. Cervicovaginal tracts from intact BALB/c mice were examined histologically and by flow cytometry at 70 days of age and by histology alone at 18 to 22 months of age. The results include several important findings: a) like E2-17beta, neonatal E2-17alpha treatment induced persistent vaginal cornification, hypospadias, vaginal concretions, and hyperproliferation in nearly 100% of the animals regardless of the secondary treatment for most groups; b) neonatal E2-17alpha treatment increased the nuclear DNA content of cervicovaginal epithelium at one-half both the level (mean DNA index of 1.02 vs 1.04) and incidence (22 vs 46% of the animals) of E2-17beta; c) short-term secondary treatment with E2-17alpha, unlike E2-17beta, did not significantly augment the increase in DNA content (13% for E2-17alpha vs 37 and 56% for control and E2-17beta, respectively); and d) neonatal administration with E2-17alpha induced adenosquamous tumors in the reproductive tract in 25% of the animals. Therefore, the biological effects (estrogenic potency) of E2-17alpha may be age dependent.


A Longitudinal Study of Determinants of Career Satisfaction in Medical Students.
There is evidence of significant career dissatisfaction among practicing physicians and those considering medicine as a profession. Most research on career satisfaction has examined practicing physicians. This study was undertaken to look at determinants of satisfaction in those at the earliest stage of their medical careers - medical students. As part of a larger study, students comprising one class at the University of Washington School of Medicine were surveyed three times over the course of their medical education. For the present study we examined measures specifically related to determinants of career satisfaction. Over time, students' sense of the importance of most measured determinants of satisfaction showed significant change, the majority of which were in the direction of decreased importance. However, most of the change was relative. That is, factors that students considered to be most important at the start of medical school continued to be most important throughout the educational experience and those factors students considered to be least important at Year 1 continued to be least important at Years 2 and 4. These findings have implications for medical education, a time when students are forming expectations that will impact their career satisfaction. In addition to information on career satisfaction, students should understand the professional values of medicine, their own values and expectations, current practice patterns, economics, and the role of advocacy.


Regulation of Protein Degradation by Proteasomes in Cancer.
Imbalance of protein homeostasis (proteostasis) is known to cause cellular malfunction, cell death, and diseases. Elaborate regulation of protein synthesis and degradation is one of the important processes in maintaining normal cellular functions. Protein degradation pathways in eukaryotes are largely divided into proteasome-mediated degradation and lysosome-mediated degradation. Proteasome is a multisubunit complex that selectively degrades 80% to 90% of cellular proteins. Proteasome-mediated degradation can be divided into 26S proteasome (20S proteasome + 19S regulatory particle) and free 20S proteasome degradation. In 1980, it was discovered that during ubiquitination process, wherein ubiquitin binds to a substrate protein in an ATP-dependent manner, ubiquitin acts as a degrading signal to degrade the substrate protein via proteasome. Conversely, 20S proteasome degrades the substrate protein without using ATP or ubiquitin because it recognizes the oxidized and structurally modified hydrophobic patch of the substrate protein. To date, most studies have focused on protein degradation via 26S proteasome. This review describes the 26S/20S proteasomal pathway of protein degradation and discusses the potential of proteasome as therapeutic targets for cancer treatment as well as against diseases caused by abnormalities in the proteolytic system.


Single-atom infrared emission in doped silicon nanocrystals.
Silicon luminescence, due to silicon being abundant, non-toxic and harmless, is a topic of pivotal importance in optoelectronics and biological imaging. However, a major challenge in developing high-efficiency silicon light sources is the relatively weak allowable transitions. This study focuses on single atom-doped silicon nanocrystals (Si NCs) and theoretically investigates the emission behavior of single atoms within a tetrahedral coordination field. Doping a single atom in Si NCs can result in a ∼102 times improvement at least in the squared transition dipole moment (TDM2), and induce a spectral shift towards near- and mid-infrared wavelengths. These findings offer a strong foundation for designing Si NCs for on-chip optical communication and single photon emitters.