An ALPHA7 Nicotinic Acetylcholine Receptor Agonist (GTS-21) Promotes C2C12 Myonuclear Accretion in Association with Release of Interleukin-6 (IL-6) and Improves Survival in Burned Mice.
The role of interleukin-6 (IL-6) in physiological processes and disease is poorly understood. The hypothesis tested in this study was that selective alpha7 acetylcholine receptor (α7AChR) agonist, GTS-21, releases IL-6 in association with myonuclear accretion and enhances insulin signaling in muscle cells, and improves survival of burn injured (BI) mice. The in vitro effects of GTS-21 were determined in C2C12 myoblasts and 7-day differentiated myotubes (myotubes). The in vivo effects of GTS-21 were tested in BI wild-type (WT) and IL-6 knockout (IL6KO) mice. GTS-21 dose-dependently (0 μM, 100 μM, and 200 μM) significantly increased IL-6 levels in myoblasts and myotubes at 6 and 9 h. GTS-21-induced IL-6 release in myotubes was attenuated by methyllycaconitine (α7AChR antagonist), and by Stat-3 or Stat-5 inhibitors. GTS-21 increased MyoD and Pax7 protein expression, myonuclear accretion, and insulin-induced phosphorylation of Akt, GSK-3β, and Glut4 in myotubes. The glucose levels of burned IL6KO mice receiving GTS-21 decreased significantly compared with sham-burn IL6KO mice. Superimposition of BI on IL6KO mice caused 100% mortality; GTS-21 reduced mortality to 75% in the IL6KO mice. The 75% mortality in burned WT mice was reduced to 0% with GTS-21. The in vitro findings suggest that GTS-21-induced IL-6 release from muscle is mediated via α7AChRs upstream of Stat-3 and -5 pathways and is associated with myonuclear accretion, possibly via MyoD and Pax7 expression. GTS-21 in vivo improves survival in burned WT mice and IL6KO mice, suggesting a potential therapeutic application of α7AChR agonists in the treatment of BI.


Spinal tumors: Trends from Northern India.
We retrospectively analyzed 111 patients with spinal tumors operated over a period of 9 years to observe the relative frequency of different lesions, their clinical profile, functional outcome and prognostic factors. 30/111 (27%) were extradural, 40/111 (36.1%) were intradural extramedullary (IDEM) and 41/111 (36.9%) were intramedullary spinal cord tumors (IMSCTs). Mean age at surgery was 30.81 years (range 1-73 years). The average preoperative duration of symptoms was 16.17 months (15 days to 15 years). Major diagnoses were ependymomas and astrocytomas in IMSCT group, schwanommas and neurofibromas in IDEM group, and metastasis, lymphoma in extradural group. The common clinical features were motor weakness in 78/111 (70.27%), sensory loss in 55/111 (49.54%), pain 46/111 (41.44%), and sphincter involvement in 47/111 (42.43%) cases. Totally, 88/111 (79.27%) patients had improvement in their functional status, 17/111 (15.31%) remained same, and 6/111 (5.4%) were worse at time of their last follow-up. The mean follow-up was 15.64 months (1.5 m(-10) years). Totally, 59 out of 79 patients, who were dependent initially, were ambulatory with or without the aid. Most common complication was persistent pain in 10/111 (9%) patients and nonimprovement of bladder/bowel symptoms in 7/111 (6.3%). One patient died 3 months after surgery. (1) Congenital malformative tumors like epidermoids/dermoids (unrelated to spina bifida) occur more frequently, whereas the incidence of spinal meningioma is less in developing countries than western populations. (2) The incidence of intramedullary tumors approaches to that of IDEM tumors. Intramedullary tumors present at a younger age in developing countries. (3) Rare histological variants like primitive neuroectodermal tumors should also be considered for histological differential diagnosis of spinal tumors. (4) Preoperative neurologic status is the most important factor related to outcome in spinal tumors.


Teaching Observation as a Faculty Development Tool in Medical Education: A Scoping Review.
Health professions education often includes teaching observation to inform faculty development (FD) and indirectly improve student performance. Although these FD approaches are well received by faculty, they remain underused and/or underreported, with limited opportunities to receive feedback in workplace contexts. The goal of our study was to map the depth and breadth of education literature on the use of observation of teaching as a tool of professional development in medical education. Following the methodology by Arksey and O'Malley, we conducted a scoping review and searched four databases for articles published in English (final searches in April 2022). Of 2080 articles identified, 45 met the inclusion criteria. All observation activities were associated with one of the following FD approaches: peer observation of teaching (23 articles, 51%), peer coaching (12, 27%), peer review (9, 20%), and the critical friends approach (1, 2%). Thirty-three articles (73%) concerned formative versions of the observation model that took place in clinical settings (21, 47%), and they tended to be a voluntary (27, 60%), one-off (18, 40%), in-person intervention (29, 65%), characterized by limited institutional support (13, 29%). Both barriers and challenges of teaching observation were identified. This review identified several challenges and shortcomings associated with teaching observation, such as inadequate methodological quality of research articles, inconsistent terminology, and limited understanding of the factors that promote long-term sustainability within FD programs. Practical strategies to consider when designing an FD program that incorporates teaching observation are outlined.


Elective transcervical superior mediastinal lymph node dissection for advanced laryngeal and level 4 N3 squamous cell carcinoma.
To review our results with elective superior mediastinal lymph node dissections in patients with advanced laryngeal squamous cell carcinoma (SCCA) and overt level 4 adenopathy. Retrospective review. We searched operative case logs for all patients treated with an elective superior mediastinal dissection by the senior author (Y.D.) during a 7-year period. Charts were reviewed for demographic information, prior treatment with chemotherapy or radiotherapy, and pathologic results. Fifty-six patients who underwent elective superior mediastinal lymph node dissection for advanced laryngeal SCCA and overt level 4 adenopathy were reviewed, and superior mediastinal disease was present in 15 of 56 (26.8%) patients. Superior mediastinal nodes were positive in 11 of 42 (26.2%) patients with advanced laryngeal SCCA and 4 of 14 (28.6%) patients with N3 SCCA involving level 4. Patients with SCCA receiving prior chemotherapy and radiotherapy had a significantly higher rate of positive superior mediastinal nodes (10/21 patients, 47.6%) compared with patients without prior therapy (5/35 patients, 14.3%, P = .01, Fisher's exact test). There were no stomal recurrences in 42 patients treated for advanced laryngeal cancer. Elective transcervical superior mediastinal dissection was positive in 26.8% of patients with advanced laryngeal cancer or N3 disease in level 4. A transcervical superior mediastinal dissection may be safely performed without a sternotomy.


Nonequilibrium Full Counting Statistics and Symmetry-Resolved Entanglement from Space-Time Duality.
Owing to its probabilistic nature, a measurement process in quantum mechanics produces a distribution of possible outcomes. This distribution-or its Fourier transform known as full counting statistics (FCS)-contains much more information than say the mean value of the measured observable, and accessing it is sometimes the only way to obtain relevant information about the system. In fact, the FCS is the limit of an even more general family of observables-the charged moments-that characterize how quantum entanglement is split in different symmetry sectors in the presence of a global symmetry. Here we consider the evolution of the FCS and of the charged moments of a U(1) charge truncated to a finite region after a global quantum quench. For large scales these quantities take a simple large-deviation form, showing two different regimes as functions of time: while for times much larger than the size of the region they approach a stationary value set by the local equilibrium state, for times shorter than region size they show a nontrivial dependence on time. We show that, whenever the initial state is also U(1) symmetric, the leading order in time of FCS and charged moments in the out-of-equilibrium regime can be determined by means of a space-time duality. Namely, it coincides with the stationary value in the system where the roles of time and space are exchanged. We use this observation to find some general properties of FCS and charged moments out of equilibrium, and to derive an exact expression for these quantities in interacting integrable models. We test this expression against exact results in the Rule 54 quantum cellular automaton and exact numerics in the XXZ spin-1/2 chain.


Two-Dimensional Self-Assembly of Au@Ag Core-Shell Nanocubes with Different Permutations for Ultrasensitive SERS Measurements.
Different self-assembly methods not only directly change the arrangement of noble metal particles on the substrate but also indirectly affect the local electromagnetic field distribution and intensity of the substrate under specific optical excitation conditions, which leads to distinguished different enhancement effects of the structure on molecular Raman signals. In this paper, first, the gold species growth method was used to prepare the silver-coated gold nanocubes (Au@Ag NCs) with regular morphology and uniform size, and then the two-phase and three-phase liquid-liquid self-assembly and evaporation-induced self-assembly methods were used to obtain the substrate structure with different NC arrangement patterns. The optimal arrangement of NCs was found by transverse comparison of Raman signal detection of probe molecules with the same concentration. Subsequently, surface-enhanced Raman scattering (SERS) measurements of Rhodamine (Rh6G) and aspartame (APM) were carried out. Furthermore, the finite element method (FEM) was employed to calculate the local electromagnetic fields of the substrates with different Au@Ag NC arrangements, and the calculated results were in agreement with the experimental results. The experimental results show that the SERS-active substrate was largely associated with the different arrangements of Au@Ag NCs, and the island membrane Au@Ag NCs array substrate obtained by evaporation-induced self-assembly can generate a strong local electromagnetic field due to the edge and corner bonding gap between the tightly arranged NCs; this endows the substrate with benign sensitivity and reproducibility and has great potential in molecular detection, biosensing, and food safety monitoring.


Ethical issues in nursing research: the wider picture.
You think you've finished writing that research proposal. It simply needs to be submitted for funding. But haven't you overlooked something? Are there not some questions still to be answered like: 'Will this research actually help patients or am I just doing this to increase my research rating, or finish this degree or to enhance my CV?'; 'Will this research project have any lasting effects on the participants?'; 'Have I been completely honest with the participants about what happens to their responses or with the exact nature of the intervention?'; 'What about those only receiving placebos, is it morally wrong to deny them the chance of improvement by placing them in the control group?'; and 'Who answers these questions anyway?'


Spatiotemporal characteristics of cerebral blood volume changes in rat somatosensory cortex evoked by sciatic nerve stimulation and obtained by optical imaging.
The spatiotemporal characteristics of changes in cerebral blood volume associated with neuronal activity were investigated in the hindlimb somatosensory cortex of alpha-chloralose-urethane anesthetized rats (n=10) with optical imaging at 570 nm through a thinned skull. Activation of the cortex was carried out by electrical stimulation of the contralateral sciatic nerve with 5-Hz, 0.3-V pulses (0.5 ms) for 2 s. The stimulation evoked a monophasic decrease in optical reflectance at the cortical parenchyma and arterial sites soon after the onset of stimulation, whereas no similar response was observed at vein compartments. The optical signal changes reached 10% of the peak response 0.70 +/- 0.32 s after the start of stimulation, and no significant time lag in this 10% start latency time was observed between the response at the cortical parenchyma and artery compartments. The decrease in optical reflectance reached a peak (0.25 +/- 0.047%) 2.66 +/- 0.61 s after stimulus onset at parenchymal sites, which is 0.40 +/- 0.20 s earlier (P<0.05) than that at arterial sites (0.50 +/- 0.068% 3.06 +/- 0.70 s). Varying the locations within the cortical parenchyma and arterial compartments did not significantly affect the temporal characteristics of the evoked signal. These results suggest that stimulation of the sciatic nerve evokes an increase in local blood volume in both capillaries (cortical parenchyma) and arterioles soon after the onset of a stimulus, but the blood volume increase evoked in capillaries could not be entirely accounted for by the dilation of arterioles.


Distribution of radioactive octacosanol in response to exercise in rats.
To study the mechanism of action of octacosanol in rats the biodistribution of radioactivity of octacosanol was investigated in response to exercise. The amount of voluntary exercise was significantly higher in octacosanol fed rats than in the control. After ingestion of 14C-octacosanol, the accumulation of radioactivity of octacosanol in the muscle of exercised group given octacosanol was significantly higher in comparison with that of the exercised control group given no octacosanol and also the non-exercised groups irrespective of whether they were given octacosanol or not. The muscle thus seemed to be able to store a considerable amount of octacosanol in response to exercise. Although the exact mechanism of increase in physical exercise caused by octacosanol is not known, it is possible that octacosanol increases the mobilization of free fatty acids from fat cells within muscle. The results indicate that octacosanol possesses an adipokinetic activity, which might affect the lipolysis process of muscle.


Satisfaction with career choice among U.S. plastic surgeons: results from a national survey.
The authors' purpose was to describe patterns and correlates of satisfaction with career choice among U.S. plastic surgeons. A mailed, self-administered survey was sent to 708 U.S. plastic surgeons who were randomly sampled from the American Society of Plastic Surgeons registry (71 percent response rate, n = 505). The dependent variable was satisfaction with the decision to become a plastic surgeon, which was created from a scale of four validated questions measuring decisional satisfaction and decisional regret. The independent variables included surgeon and practice characteristics. Logistic regression was used to evaluate associations between satisfaction with the decision to become a plastic surgeon and independent factors. Few respondents (4 percent) regretted becoming plastic surgeons. Factors independently associated with greater satisfaction with the decision to become a plastic surgeon included group practice compared with solo practice (odds ratio, 1.65; 95 percent confidence interval, 1.0 to 2.71), resident educator (odds ratio, 1.88; 95 percent confidence interval, 1.06 to 3.31), and a highly cosmetic practice mix: primarily cosmetic versus primarily reconstructive (odds ratio, 2.42; 95 percent confidence interval, 1.25 to 4.66) and mixed versus primarily reconstructive (odds ratio, 1.59, 95 percent confidence interval, 0.92 to 2.76). Demographic factors such as age and gender were not associated with surgeon satisfaction. Overall, the majority of plastic surgeons are satisfied with their career choice despite the current health care and economic environment. Factors significantly associated with greater satisfaction with career choice included group practice, involvement in resident education, and a highly elective cosmetic practice.


Towards a framework to assess, compare and develop monitoring and evaluation of climate change adaptation in Europe.
Adaptation is increasingly recognised as essential when dealing with the adverse impacts of climate change on societies, economies and the environment. However, there is insufficient information about the effectiveness of adaption policies, measures and actions. For this reason, the establishment of monitoring programmes is considered to be necessary. Such programmes can contribute to knowledge, learning and data to support adaptation governance. In the European Union (EU), member states are encouraged to develop National Adaptation Strategies (NASs). The NASs developed so far vary widely because of differing views, approaches and policies. A number of member states have progressed to monitoring and evaluating the implementation of their NAS. It is possible to identify key elements in these monitoring programmes that can inform the wider policy learning process. In this paper, four generic building blocks for creating a monitoring and evaluation programme are proposed: (1) definition of the system of interest, (2) selection of a set of indicators, (3) identification of the organisations responsible for monitoring and (4) definition of monitoring and evaluation procedures. The monitoring programmes for NAS in three member states-Finland, the UK and Germany-were analysed to show how these elements have been used in practice, taking into account their specific contexts. It is asserted that the provision of a common framework incorporating these elements will help other member states and organisations within them in setting up and improving their adaptation monitoring programmes.


Stability and compatibility assessment techniques for total parenteral nutrition admixtures: setting the bar according to pharmacopeial standards.
The stability and compatibility of total parenteral nutrition mixtures compounded for patients requiring nutritional support is paramount to their safety on intravenous infusion. The most significant pharmaceutical issues associated with mixing total parenteral nutrition formulations affecting their safety involve the stability of lipid-injectable emulsions and the compatibility of calcium and phosphate salts. Methods of analysis for stability and compatibility have varied, and the assessments have mostly been largely qualitative. Although pharmacopeial standards have been primarily applicable to pharmaceutical manufacturers, recent efforts by the United States Pharmacopeia have been directed at standardizing pharmacy practices involved in the safe mixing of compounded sterile preparations. The adoption of chapter 797 entitled 'Pharmaceutical compounding - sterile preparations' on 1 January 2004 has had a dramatic impact on pharmacy practice in the United States. More recently, the United States Pharmacopeia has also proposed a new chapter 729 entitled 'Globule size distribution in lipid-injectable emulsions', setting specific limits on the sizes and concentrations of lipid droplets in the formulation, which may have implications for all-in-one mixtures. Finally, new efforts are under way to establish limits on the level of acceptable amounts of particulates intrinsically introduced by the manufacturer, and thus may have ramifications for particulates extrinsically introduced or initiated during compounding by the pharmacist. With careful monitoring and the development of appropriate pharmacopeial-based specifications that limit the size and concentration of large-diameter fat globules and eliminate the possibility of dibasic calcium phosphate precipitates, improved patient outcomes may be achieved.


Changes in the determinants of fertility in Korea: analyses of pregnancy intervals and outcomes.
Korea completed the whole process of what is called the demographic transition to a low fertility and mortality level with the successful implementation of the national family planning program in 1962, and this has been accompanied by rapid socioeconomic development. Most of the fertility decline was due to a rising age at marriage and to lower marital fertility. The national family planning program, combined with the widespread practice of induced abortion, has placed an important role in reducing marital fertility, particularly among older women. This paper aims, therefore, to examine the determinants of fertility and their changes over time in an effort to suggest future population policy directions for Korea. The analysis is divided into 2 parts-estimation of pregnancy intervals by applying the proportional hazards model, and estimation of the determinants of fertility by adopting the logistic regression model to find out whether a pregnancy terminates in a live birth or in an abortion. In both analyses, the sex was included as the main explanatory variable. A woman's education has been shown to have a significant effect on delaying the timing or on the wife's age at first pregnancy, but its effect on the pace of subsequent pregnancies is much smaller and often positive. On the other hand, the woman's education has a consistently positive effect on the probability of a pregnancy ending in an abortion although the effect shows a steady decline over time. Form first parity, the sex composition of previous children stands out consistently as the most important factor in deciding both the pace of pregnancy and its outcome. The pregnancy risks of the women with sons are reduced by almost 50% at the second and third parities. The probability of a pregnancy ending in an abortion also increases substantially when parents already have a son. The decline of the desired family size but the sustained strong son preference has made the sex of children a more important factor in the determination of Korean fertility. The woman's education, on the other hand, has become a less important factor.


Clinical impact of whole-body 68Ga-PSMA I&T PET/CT: lesion frequency and added benefit in lower extremities.
Few small-scaled studies performed systematic analysis of the benefits of extending prostate specific membrane antigen positron-emission tomography/ computed tomography (68Ga-PSMA I&T PET/CT) to the lower extremities in prostate cancer (PCa) patients. We hypothesized that 68Ga-PSMA I&T PET/CT positive lesions are rare in lower extremities of prostate cancer (PCa) patients, the clinical implication is negligible and may therefore be omitted. We retrospectively analyzed 1,068 PCa patients who received 68Ga-PSMA I&T PET/CT in a single institution (2016-2018). Of those, 285 (26.7%) were newly diagnosed, 529 (49.5%) had biochemical recurrence (BCR) and 254 (23.8%) were castration-resistant prostate cancer (CRPC) patients. Of 1,068 68Ga-PSMA I&T PET/CTs, positive lesions in the lower extremities were identified in 6.9% patients (n=74). Positive lesions in the lower extremities were most common in CRPC patients (19.7%; n=50), followed by newly diagnosed (3.2%; n=9) and BCR (2.8%; n=15) PCa patients. Only 3 patients presented with exclusive lesions in the lower extremities, respectively 0.8% (n=2) in CRPC and 0.4% (n=1) in newly diagnosed PCa. Both CRPC (94.1%, n=47) and BCR (80.0%, n=12) patients with PSMA-positive lesions predominantly received systemic therapy. Identification of lower extremities lesions with PSMA PET/CT is uncommon and exclusive lesions are rare. PSMA PET/CT findings of the lower extremities did not change therapy management. Thus, scanning of the lower extremities can be omitted in standard protocols.


Something's "Fishy" With That Sore Throat...
A 9-year old male presented to the emergency department for the evaluation of a sore throat. Initial history of present illness stated in the triage note was that "the child complained of a sore throat," suggesting possible pharyngitis. There was no evidence of stridor, sialorrhea, hypoxia, or aphonia. Further investigation of the history of present illness identified the concern for a possible esophageal foreign body. Imaging studies of the neck identified a fishbone in the esophagus. This case presentation discusses an atypical presentation of an esophageal foreign body and the subtle findings on assessment and imaging. This case highlights the importance of illiciting a history of present illness and the subtleties of esophageal foreign body identification.


The relationship between fetal breathing movements and prostaglandin E2 during ACTH-induced labour in sheep.
We measured fetal breathing movements and fetal carotid arterial prostaglandin E concentrations during adrenocorticotrophin-induced labour in 6 pregnant sheep and in 6 control animals starting at day 127. The 6 ACTH-treated animals went into labour on average 97 h after the onset of infusion and the incidence of fetal breathing movements diminished during the last 12h before the onset of labour. There was a significant negative relationship between the incidence of fetal breathing movements and fetal carotid arterial prostaglandin E concentrations (r = -0.88; P less than 0.001) in ACTH treated animals. These data suggest a role for prostaglandin E in the diminution of fetal breathing movements prior to the onset of labour.


Five immune-related genes as diagnostic markers for endometriosis and their correlation with immune infiltration.
Endometriosis (EMS) is a chronic disease that can cause dysmenorrhea, chronic pelvic pain, and infertility, among other symptoms. EMS diagnosis is often delayed compared to other chronic diseases, and there are currently no accurate, easily accessible, and non-invasive diagnostic tools. Therefore, it is important to elucidate the mechanism of EMS and explore potential biomarkers and diagnostic tools for its accurate diagnosis and treatment. In the present study, we comprehensively analyzed the differential expression, immune infiltration, and interactions of EMS-related genes in three Homo sapiens datasets. Our results identified 332 differentially expressed genes (DEGs) associated with EMS. Gene ontology analysis showed that these changes mainly focused on the positive regulation of endometrial cell proliferation, cell metabolism, and extracellular space, and EMS involved the integrin, complement activation, folic acid metabolism, interleukin, and lipid signaling pathways. The LASSO regression model was established using immune DEGs with an area under the curve of 0.783 for the internal dataset and 0.656 for the external dataset. Five genes with diagnostic value, ACKR1, LMNB1, MFAP4, NMU, and SEMA3C, were screened from M1 and M2 macrophages, activated mast cells, neutrophils, natural killer cells, follicular T helper cells, CD8+, and CD4+ cells. A protein-protein interaction network based on the immune DEGs was constructed, and ten hub genes with the highest scores were identified. Our results may provide a framework for the development of pathological molecular networks in EMS.


Group B arbovirus structural and nonstructural antigens. II. Purification of Saint Louis encephalitis virus intracellular antigens.
Three serologically distinct antigens were identified in homogenates of Saint Louis encephalitis (SLE) virus-infected cells after Brij-58 solubilization and diethylaminoethyl (DEAE)-cellulose chromatography. These antigens were designated as antigen I, II, and III. Immunodiffusion analyses showed that all antigen peaks which eluted from the DEAE-cellulose column contained the intracellular major envelope protein, antigen I. This protein was the only viral antigen which eluted at 0.125 M KCl in DEAE-cellulose column peak C. Optical density peak D, which eluted at 0.2 M KCl, contained both antigens I and III. Antigen III was purified from this column fraction approximately 200-fold by organic solvent extraction and chromatography on hydroxylapatite and Sepharose 6B. Purified antigen III had a molecular weight of 80,000 to 85,000 and contained only one antigenic determinant as judged by immunodiffusion analysis.


Distal Revascularization And Interval Ligation Procedure For The Treatment Of Dialysis Access Induced Steal Syndrome.
We aim to share our experience of the efficacy of Distal Revascularization and Interval Ligation (DRIL) in alleviating ischemic symptoms of dialysis access induced steal syndrome (DAISS) while preserving the original access. In this multicentre study, all consecutive patients with DAISS undergoing DRIL over a period of 3 years were included. A total of 25 DRILs were included. Mean age was 37.8±SD 7.8 years and 52% (n=13) were females. Out of 25 patients; 88% (n=22) had more than one of the following ischemic symptoms: coolness (96%), pain (88%), paresthesia (80%), and discoloration (44%). Significant improvement following DRIL was noted in paraesthesia (86%, p-value 0.00), pain (85%, P value 0.00), coolness (83%, p-value 0.00). There was significant improvement in distal blood flow following DRIL, reflected by increase in the Aggregate Peak Systolic Velocities (PSV) in forearm vessels (PSV aggregate pre-op 39cm/s: PSV aggregate post-op 58 cm/s; p-value 0.01). The cumulative patency of DRIL graft was 96% at 3 months, 84% at 6 months and 76% at 1 year. Distal Revascularization and Interval Ligation significantly improves circulation to the distal limb and reduce ischemic symptoms thus making it a procedure of choice for treatment of DAISS.


Management of localized gingival recession by two-stage surgical procedure - Double pedicle flap with CTG and coronally advanced flap: A novel technique.
Cosmetic treatments have become an integral part of periodontal treatment. One of the commonly used esthetic periodontal procedures is coverage of denuded root surface. While considering the elimination of these defects two criteria should be considered, the esthetic aspects and the functional aspects. This case report has describes a two stage surgical technique using double pedicle flap with connective tissue graft followed by coronally advanced flap for the treatment of a severe localized gingival recession measuring 15 mm. The recession measurement at the end of 12 months was 1 mm. It showed a predictable result at the end of one year. The advantages of this technique are excellent colour matching, dual blood supply to graft and very predictable results. The promising result suggest that this technique can be used in severe gingival recession cases with minimum amount of keratinized tissue.


Cancer prevention by phytochemicals.
Information has been accumulated indicating that diets rich in vegetables and fruits can reduce the risk of a number of chronic diseases, including cancer, cardiovascular disease, diabetes and age-related macular degeneration. Phytochemicals (various factors in plant foods), such as carotenoids, antioxidative vitamins, phenolic compounds, terpenoids, steroids, indoles and fibers, have been considered responsible for the risk reduction. Among them, a mixture of natural carotenoids has been studied extensively and proven to show beneficial effects on human cancer prevention.


Multi-Target Intense Human Motion Analysis and Detection Using Channel State Information.
Intense human motion, such as hitting, kicking, and falling, in some particular scenes indicates the occurrence of abnormal events like violence and school bullying. Camera-based human motion detection is an effective way to analyze human behavior and detect intense human motion. However, even if the camera is properly deployed, it will still generate blind spots. Moreover, camera-based methods cannot be used in places such as restrooms and dressing rooms due to privacy issues. In this paper, we propose a multi-target intense human motion detection scheme using commercial Wi-Fi infrastructures. Compared with human daily activities, intense human motion usually has the characteristics of intensity, rapid change, irregularity, large amplitude, and continuity. We studied the changing pattern of Channel State Information (CSI) influenced by intense human motion, and extracted features in the pattern by conducting a large number of experiments. Considering occlusion exists in some complex scenarios, we distinguished the Line-of-Sight (LOS) and Non-Line-of-Sight (NLOS) conditions in the case of obstacles appearing between the transmitter and the receiver, which further improves the overall performance. We implemented the intense human motion detection system using single commercial Wi-Fi devices, and evaluated it in real indoor environments. The experimental results show that our system can achieve intense human motion detection rate of 90%.


Optogenetic control of the guard cell membrane potential and stomatal movement by the light-gated anion channel GtACR1.
Guard cells control the aperture of plant stomata, which are crucial for global fluxes of CO2 and water. In turn, guard cell anion channels are seen as key players for stomatal closure, but is activation of these channels sufficient to limit plant water loss? To answer this open question, we used an optogenetic approach based on the light-gated anion channelrhodopsin 1 (GtACR1). In tobacco guard cells that express GtACR1, blue- and green-light pulses elicit Cl- and NO3 - currents of -1 to -2 nA. The anion currents depolarize the plasma membrane by 60 to 80 mV, which causes opening of voltage-gated K+ channels and the extrusion of K+ As a result, continuous stimulation with green light leads to loss of guard cell turgor and closure of stomata at conditions that provoke stomatal opening in wild type. GtACR1 optogenetics thus provides unequivocal evidence that opening of anion channels is sufficient to close stomata.


A brief introduction to cell-penetrating peptides.
Cell membranes act as protective walls to exclude most molecules that are not actively imported by living cells. This is an efficient way for a cell to prevent uncontrolled influx or efflux of solutes, which otherwise would be harmful to it. Only compounds within a narrow range of molecular size, polarity and net charge are able to diffuse effectively through cell membranes. In order to overcome this barrier for effective delivery of membrane-impermeable molecules, several chemical and physical methods have been developed. These methods, e.g. electroporation, and more recent methods as cationic lipids/liposomes, have been shown to be effective for delivering hydrophobic macromolecules. The drawbacks of these harsh methods are, primarily, the unwanted cellular effects exerted by them, and, secondly, their limitation to in vitro applications. The last decade's discovery of cell-penetrating peptides translocating themselves across cell membranes of various cell lines, along with a cargo 100-fold their own size, via a seemingly energy-independent process, opens up the possibility for efficient delivery of DNA, antisense peptide nucleic acids, oligonucleotides, proteins and small molecules into cells both in vitro and in vivo.


Catabolite repression in the facultative chemoautotroph Thiobacillus novellus.
Several fermentable carbon sources were found to give rise to catabolite repression of all enzymes implicated in thiosulfate oxidation in the facultative chemoautotroph, Thiobacillus novellus. Glucose was found to elicit a strong repression. Glycerol, lactate, lactose, ribose, and pyruvate caused marked repression. In all cases, the repression could be relieved only by returning the cells to a medium devoid of such fermentable substrates. On the other hand, carbon compounds (amino acids and organic acids) that are metabolizable only aerobically caused transient or no repression of the thiosulfate oxidative system. All of the enzymes believed to participate in thiosulfate oxidation, except tetrathionase, were found to be simultaneously induced and repressed. This would suggest that tetrathionate may not be a necessary intermediate in the thiosulfate-oxidation pathway of T. novellus.


Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab.
In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.


Mechanism of action and determinants of sensitivity to the proteasome inhibitor bortezomib in multiple myeloma therapy.
Bortezomib (BTZ), a proteasome inhibitor, has been widely used for the treatment of multiple myeloma (MM), including newly diagnosed as well as relapsed and refractory cases, and is considered to be a key drug in the induction therapy for MM. However, the precise mechanism underlying the action of this agent has yet to be fully elucidated. Predicting sensitivity to BTZ treatment by using adequate biomarkers would aid in the development of individual targeted therapies for MM. Herein, by reviewing preclinical studies using MM cell lines and other investigations that have analyzed primary MM samples from patients, we describe in detail the induction of MM cell death by proteasome inhibition and the factors that regulate the sensitivity of the proteasome inhibitor BTZ in MM cells.


Post biphosphonate mandible osteonecrosis: A case study and literature review.
Bisphosphonates have proven effective in reducing pain and skeletal events in bone metastases treatment. However, there is a long-term complication called osteonecrosis of the jaw, which has been reported for more than a decade. Despite various professional recommendations, there is no international consensus on the best therapeutic strategy. Prevention is crucial, and a multidisciplinary approach must be tailored to each stage of the condition. We present a case of osteonecrosis of the jaw in a patient with metastatic breast cancer who was receiving 4 mg injectable zoledronic acid. The patient stopped treatment with zoledronic acid and received systemic treatment (analgesics, antibiotics), with the resolution of symptoms. ONJ is a serious condition associated with taking BP that can impact oral health and quality of life. Our study highlights the effectiveness of systematic treatment in managing ONJ with BP-related alterations. Preventative measures, such as regular dental consultations, play a vital role in reducing the risk of ONJ. Multidisciplinary management is essential to addressing the different stages of the condition.


A Dynamic Endonasal Columellar Strut Placement.
The dynamic retrograde intercrural columellar strut graft placement is a novel technique for a columellar strut insertion via a hemi-transfixion incision in patients undergoing endonasal functional or cosmetic surgery. It has a maximally concealed incision and does not disrupt major or minor tip support mechanisms. In our article, we give a detailed description of this unique surgical technique. Laryngoscope, 2023.


Chemical composition of essential oils of Litsea cubeba harvested from its distribution areas in China.
Litsea cubeba (Lour.) Pers. is a promising industrial crop with fruits rich in essential oils. The chemical composition of essential oils of L. cubeba (EOLC) were determined for fruits harvested from eight regions in China. The overall essential oil content, obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS), ranged from 3.04% to 4.56%. In total, 59 compounds were identified, the dominant components being monoterpenes (94.4-98.4%), represented mainly by neral and geranial (78.7-87.4%). D-Limonene was unexpectedly a lesser constituent (0.7-5.3%) in fruits, which differed from previous reports (6.0-14.6%). Several components were only detected in certain regions and compounds such as o-cymene and eremophilene have never before been reported in EOLC. These results demonstrate significant regional variation in the chemical composition of EOLC. This investigation provides important information with regard to the bioactivity, breeding work and industrial applications of L. cubeba.


Do not be scared of the genome's 5th base-Explaining phenotypic variability and evolutionary dynamics through DNA methylation analysis.
Epigenetic processes have taken center stage for the investigation of many biological processes, and epigenetic modifications have shown to influence phenotype, morphology and behavioural traits such as stress resistance by affecting gene regulation and expression without altering the underlying genomic sequence. The multiple molecular layers of epigenetics synergistically construct the cell type-specific gene regulatory networks, characterized by a high degree of plasticity and redundancy to create cell-type-specific morphology and function. DNA methylation occurring on the 5' carbon of cytosines in different genomic sequence contexts is the most studied epigenetic modification. DNA methylation has been shown to provide a molecular record of the exposure to a large variety of environmental factors, which might be persistent through the entire lifetime of an organism and even be passed onto the offspring. Animals might display altered phenotypes mediated by epigenetic modifications depending on the developmental stage or the environmental conditions as well as during evolution. Therefore, the analysis of DNA methylation patterns might allow deciphering previous exposures, explaining ecologically relevant phenotypic diversity and predicting evolutionary trajectories enabling accelerated adaption to changing environmental conditions. Despite the explanatory potential of DNA methylation integrating genetic and environmental factors to shape phenotypic variation and contribute significantly to evolutionary dynamics, studies of DNA methylation are still scarce in the field of ecology. This might be at least partly due to the complexity of DNA methylation analysis and the interpretation of the acquired data. In the current issue of Molecular Ecology Resources, Laine and colleagues (Molecular Ecology Resources, 2022) provide a detailed summary of guidelines and valuable recommendations for researchers in the field of ecology to avoid common pitfalls and perform interpretable genome-wide DNA methylation analyses.


Carcinoma of bronchus and the smoking habit in Rhodesian Africans.
Comparison of the smoking habits of 32 adult male Africans with carcinoma of the bronchus and 32 controls showed that 87.5% of the patients with lung cancer were cigarette smokers compared with only 22% of the controls. The distribution of histological types of growth confirmed findings by other workers.The absence of atmospheric pollution in Rhodesia makes it likely that cigarette-smoking is the most important causative factor in the aetiology of lung cancer among Rhodesian Africans. Further work is needed to determine the level of consumption of cigarettes and type of smoking habits which lead to a serious risk of cancer.


Antidiarrhoeal effects of methanolic root extract of Hemidesmus indicus (Indian sarsaparilla)--an in vitro and in vivo study.
Methanolic extract of H. indicus root (MHI) was screened for its antimicrobial activity against S. typhimurium, E. coli and S. flexneri, in vitro and in experimentally induced diarrhoea in albino rats, in vivo. MHI had an anti enterobacteriae effect as evident from agar well diffusion method and decrease in CFU/ml in MHI treated LB broth culture. MHI inhibited the castor oil induced diarrhoea in rats as judged by a decrease in the amount of wet faeces in MHI-pretreated rats at a dose of 500-1500 mg/kg. The results indicated that MHI was more active than standard antidiarrhoeal drug, lomotil. Phytochemical tests revealed the main constituents as tannins, steroids, triterpenoids and carbohydrates. Present findings suggested that MHI might elicit an antidiarrhoeal effect by inhibition of intestinal motility and by its bacteriocidal activity.


[The quantitative determination of vitamin D3 and its metabolites in plasma].
A method is described which enables determination of vitamin D3 and its physiologically most important metabolites, i.e. 25-OHD3, 24,25-(OH)2D3, 25,26-(OH)2D3 and 1,25-(OH)2D3 in a plasma sample of about 2 to 4 ml. The whole procedure involves two preparative and one analytical steps: Extraction with methanol/methylene chloride (2:1), chromatographic separation on Lipidex 5000 using a stepwise gradient of n-hexane and chloroform and finally HPLC separation on Zorbax-Sil columns with n-hexane isopropanol mixtures and subsequently reversed phase separation on RP 18-columns and mixtures of methanol and water. Except for 1,25-(OH)2D3 all D compounds were quantified by UV-detection with 1.4 ng of substance being the lowest detectable amount. 1,25-(OH)2D3 was measured by radioimmunoassay. Prior to HPLC analysis the extract was separated into three fractions on Lipidex 5000 which contained 1) vitamin D3, 2) 25-OHD3 and 3) the dihydroxy metabolites. The three fractions were separated by HPLC using different mixtures of isopropanol/n-hexane and methanol/water, respectively. Retention times of the individual D-components longer than 10 min appeared to be essential to separate these compounds from accompanying material. Overall recoveries of the individual metabolites were for vitamin D3 48.9%, for 25-OHD3 54.2%, for 24,25-(OH)2D3 50.9% and for 1,25-(OH)2D3 52.5%. Application of the methods to plasma samples from pigs with pseudovitamin D deficiency rickets, typ I, revealed a reduced concentration of 1,25-(OH)2D3 and 24,25-(OH)2D3 and an elevated level of 25-OHD3 in these animals. The results obtained by this method contributed substantially to a better understanding of the aetiological factors associated with this disease.


Forced nonlinear Schrödinger equation with arbitrary nonlinearity.
We consider the nonlinear Schrödinger equation (NLSE) in 1+1 dimension with scalar-scalar self-interaction g(2)/κ+1(ψ*ψ)(κ+1) in the presence of the external forcing terms of the form re(-i(kx+θ))-δψ. We find new exact solutions for this problem and show that the solitary wave momentum is conserved in a moving frame where v(k)=2k. These new exact solutions reduce to the constant phase solutions of the unforced problem when r→0. In particular we study the behavior of solitary wave solutions in the presence of these external forces in a variational approximation which allows the position, momentum, width, and phase of these waves to vary in time. We show that the stationary solutions of the variational equations include a solution close to the exact one and we study small oscillations around all the stationary solutions. We postulate that the dynamical condition for instability is that dp(t)/dq ̇(t)<0, where p(t) is the normalized canonical momentum p(t)=1/M(t)∂L/∂q ̇, and q ̇(t) is the solitary wave velocity. Here M(t)=∫dxψ*(x,t)ψ(x,t). Stability is also studied using a "phase portrait" of the soliton, where its dynamics is represented by two-dimensional projections of its trajectory in the four-dimensional space of collective coordinates. The criterion for stability of a soliton is that its trajectory is a closed single curve with a positive sense of rotation around a fixed point. We investigate the accuracy of our variational approximation and these criteria using numerical simulations of the NLSE. We find that our criteria work quite well when the magnitude of the forcing term is small compared to the amplitude of the unforced solitary wave. In this regime the variational approximation captures quite well the behavior of the solitary wave.


Hospital mortality in acute myocardial infarction.
All 757 patients with acute myocardial infarction admitted to the three public hospitals in Auckland during one year were studied. About 7% died from cardiac arrhythmia four days or more after the onset of infarction. These patients had severe infarcts with circulatory failure on or shortly after admission to hospital. Late death from arrhythmia in patients recovering from circulatory failure may in many cases be preventable with anti-arrhythmic drugs.


Anti-phospholipid antibodies and reproductive failures.
Anti-phospholipid syndrome (APS) recapitulates the link between autoimmunity and pregnancy failure: Acquired anti-phospholipid antibodies (aPL) play a pathogenic role in pregnancy complications. The diagnosis of obstetric APS can easily be pursued when women present with laboratory and clinical features fulfilling the international classification criteria. Standard therapeutic approach to obstetric APS consists in the association of anti-platelet agents and anticoagulants. Most patients achieve a live birth thanks to conventional treatment; however, approximately 20% fail to respond and are managed with additional therapeutic tools added on the top of conventional treatment. Surely, a refinement of risk stratification tools would allow early identification of high-risk pregnancies that warrant tailored treatment. In real life, obstetricians and rheumatologists face complex diagnostic scenarios including women with pregnancy morbidities other than those mentioned in classification criteria such as one or two early losses and premature birth after 34 weeks due to preeclampsia or placental insufficiency, women with low-titer aPL not fulfilling criteria laboratory requirements, women with positive non-criteria aPL, asymptomatic aPL carriers, and infertile women found to be aPL-positive. This review focuses on some of the several unanswered questions related to diagnostic, prognostic, and therapeutic aspects in obstetric APS.


Top-down and bottom-up proteomics of SDS-containing solutions following mass-based separation.
SDS has recognized benefits for protein sample preparation, including solubilization and imparting molecular weight separation (e.g., SDS-PAGE). Here, we compare two proteome workflows which incorporate SDS for protein separation, namely, SDS-PAGE coupled to LC/MS (GeLC MS), along with a solution separation platform, GELFrEE, for intact proteome prefractionation and identification. Despite the clear importance of SDS in these and other proteome analysis workflows, the affect of SDS on an LC/MS proteome experiment has not been quantified. We first examined the influence of SDS on both a bottom-up as well as a top-down (intact protein) MS workflow. Surprisingly, at levels up to 0.01% SDS in the injected sample, reliable MS characterization is obtained. We subsequently explored organic precipitation protocols (chloroform/methanol/water and acetone) as a means of lowering SDS, and present a simple modified acetone precipitation protocol which consistently enables MS proteome characterizations from samples initially containing 2% SDS. With this effective strategy for SDS reduction, the GELFrEE MS workflow for bottom-up proteome analysis was characterized relative to GeLC MS. Remarkable agreement in the number and type of identified proteins was obtained from these two separation platforms, validating the use of SDS in solution-phase proteome analysis.


Amended safety assessment of Hypericum perforatum-derived ingredients as used in cosmetics.
The Cosmetic Ingredient Review Expert Panel (Panel) has issued an amended safety assessment of 7 Hypericum perforatum-derived ingredients as used in cosmetics. A common name for this plant is St John wort. These ingredients function in cosmetics as skin-conditioning agents-miscellaneous and antimicrobial agents. The Panel reviewed relevant animal and human data related to the H perforatum-derived ingredients. Because formulators may use more than 1 botanical ingredient in a formulation, caution was urged to avoid levels of toxicological concern for constituent chemicals and impurities. The Panel concluded that H perforatum-derived ingredients were safe as cosmetic ingredients in the practices of use and concentration as described in this safety assessment.


[In vitro effect of interferon alpha on proliferation of human marrow fibroblast].
To explore the effect of interferon alpha (IFN-alpha) on proliferation of human marrow fibroblasts. Marrow fibroblasts were isolated from patients with iron deficiency anemia. Platelet derived growth factor-AB (PDGF-AB), transforming growth factor-beta1 (TGF-beta1) or INF-alpha2b was added in the cell cultures each alone or in combinations. Cell proliferation and cell cycle of fibroblasts were detected by MTT and flow cytometry, respectively. PDGF-ABqa (1 approximately 50 ng/ml) or TGF-beta1 (0.01 approximately 1 ng/ml) could stimulate the proliferation of the fibroblasts, while PDGF-AB was more effective (P < 0.01). IFN-alpha2b partially suppressed PDGF-AB induced proliferation of fibroblasts,the inhibition rate was 7.62%. IFN-alpha2b and TGF-beta1 combination suppressed synergistically not only the proliferation of the fibroblasts (P < 0.01) but also the PDGF-AB induced-proliferation (P < 0.01) at S phase. IFN-alpha2b combined with TGF-beta1 could synergistically suppress the PDGF-AB induced proliferation of fibroblasts at S phase in vitro.


Immunological findings in psychotic syndromes: a tertiary care hospital's CSF sample of 180 patients.
Immunological mechanisms and therapy approaches in psychotic syndromes were recently supported by the discovery of autoantibody-associated limbic and non-limbic encephalitis. However, how clinical diagnostic procedures in psychiatry should be adapted to these new insights is still unclear. In this study, we analyzed the cerebrospinal fluid (CSF) and neuroimmunological alterations and their association with cerebral MRI (cMRI) and electroencephalographic (EEG) findings. From 2006 to 2013, we acquired 180 CSF samples from psychotic patients. Between 2006 and 2009, CSF examinations were only performed in cases in which organic brain disease was suspected. Since then, this procedure has been integrated into our routine diagnostic workup. CSF basic diagnostics were supplemented by measuring antineuronal antibodies against intracellular synaptic antigens, antibodies against intracellular onconeural antigens, antibodies against neuronal cell surface antigens and thyroid antibodies. In addition, cMRIs and EEGs were conducted. We found white cell counts elevated in 3.4% of the cases, albumin quotient elevated in 21.8%, and protein concentration elevated in 42.2%. Evidence of intrathecal immunoglobulin synthesis was found in 7.2% of the cases. Antibodies measured against neuronal cell surface antigens were positive in 3.2%. Reactivity on antibodies against intracellular onconeural antigens were detected in 3.5%. Serum thyroid antibodies were elevated in 24.7%. Abnormalities were found in 39.5% of cMRIs and in 34.3% of EEGs. The main finding of our study was the high prevalence of CSF and autoantibody abnormalities in 54.4% of psychotic patients. In combination with cMRIs and EEGs, 75.6% showed abnormal findings. Our results are discussed with regard to the concept of immunological encephalopathy. Future studies should analyze the efficacy of immunomodulatory therapies.


(1-Beta-mercaptopropionic acid, 2-(3,5-dibromo-L-tyrosine))oxytocin, a potent inhibitor of oxytocin.
[1-Beta-Mercaptopropionic acid,2-(3,5-dibromo-L-tyrosine)]oxytocin was synthesized from a protected polypeptide intermediate that had been prepared by the condensation of S-ethylcarbamoyl-beta-mercaptopropionyl-3,5-dibromotyrosine with H-Ile-Gln-Asn-Cys(Ec)-Pro-Leu-Gly-NH2, using dicyclohexylcarbodiimide in dimethylformamide. The ethylcarbamoyl (Ec) protecting groups were removed by refluxing NH3, and the resulting disulfhydryl peptide was oxidatively cyclized to the corresponding disulfide by ICH2CH2I. Purification of the analog was effected by partition chromatography and gel filtration. The analog possesses antioxytocic (pA2 = 7.05) and antiavian vasodepressor (pA2 = 7.44) activities but has neither agonist nor antagonist activity in the rat pressor assay.


[Smoking cessation--a central role for physicians].
Physicians are in a unique position to advice smokers to quit by the ability to integrate the various aspects of nicotine dependence. This review provides an overview of intervention with smokers presenting in a primary care setting. Strategies used for smoking cessation counseling differed according to patient's readiness to quit. For smokers who do not intend to quit smoking, physicians should inform and sensitize patients about tobacco use and cessation, especially by personalizing benefits to quit and challenging smokers 'beliefs. For smokers who are dissonant, physicians should use motivational strategies, such as discussing barriers to cessation and their solutions. For smokers ready to quit, the physician should show strong support, help set a quit date, prescribe pharmaceutical therapies for nicotine dependence, such as replacement therapy and/or bupropion, with instructions for use, and suggest behavioral strategies to prevent relapse.


Retrieving the Talbot length of arbitrary 2D gratings.
The Talbot effect has been revived in many fields of modern optics. As a key number of self-imaging, the fundamental Talbot length plays a crucial role in many applications. However, the inspection of the Talbot carpet for determining the Talbot length is applicable only if the 2D field distribution behind the grating is represented by a 1D cross section. In this Letter, we show an effective way to overcome this limitation to explore the self-imaging of gratings with complex 2D periodicities. For that purpose, the near-field diffraction is analyzed using the Pearson correlation coefficient of the intensity distribution in Fourier space. We report results on linear, ring, and spiral gratings.


Hospital-based epidemiological and clinical characterisation of the malignant transformation of oral leukoplakia in a Chinese population.
The aim of this review was to analyse, systematically, hospital-based epidemiological information concerning the malignant transformation rate (MTR) of oral leukoplakia (OL) in a Chinese population, as well as the associated risk factors. Four electronic databases were searched for studies dealing with OL and related risk factors, including age, gender, type of lesion, site, and smoking and drinking habits. The MTR of OL in the hospital-based Chinese population ranged from 4% to 13%, based on the studies analysed. Regarding risk factors, we found that female patients had a higher MTR than male patients, and that patients older than 50 years of age also had a higher MTR. Patients who smoked had a lower MTR, while alcohol consumption seemed to have no association with MTR. Malignant transformation occurred most commonly on the tongue. Regarding lesion type, non-homogeneous OL had a higher MTR, with the granular type having the highest MTR. Our results regarding the epidemiology of OL showed a similar trend to those reported in western populations and provided preliminary epidemiological information on the Chinese population. Our findings show that female gender, age >50 years and non-homogeneous OL are risk factors for malignant transformation. It is important to develop clinical strategies to educate, diagnose and treat patients with OL and to minimise the MTR of OL.


Comparison of norepinephrine- and veratrine-induced phosphoinositide hydrolysis in rat brain.
Stimulation of phosphoinositide hydrolysis by depolarization with veratrine was compared to that produced by stimulation of alpha-1 adrenoceptors by norepinephrine. The phosphoinositides in rat cerebral cortex were labeled with [myo-3H]inositol and the effects of the drugs on the formation of the following inositol phosphates were determined: inositol 1-phosphate (IP); inositol 1,4-bisphosphate (IP2); mixture of inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate (IP3). Termination of the hydrolysis by trichloroacetic acid resulted in lower basal levels and more reproducible results than termination by water lysis or a chloroform-methanol mixture (CHCl3-MeOH). The amounts of IP and IP2 formed by a maximal concentration of veratrine were about one half of that formed by a maximal concentration of norepinephrine although the amount of IP3 formed after stimulation by veratrine was only about 10% of that produced by norepinephrine. The increase in IP was linear with time (30 min) for both norepinephrine and veratrine. Stimulation of IP2 and IP3 formation by veratrine reached a maximum at 5 min whereas that produced by norepinephrine continued to increase for 30 min. Blockade of voltage-dependent calcium channels with manganese produced nearly complete antagonism of the veratrine response while only partially antagonizing the norepinephrine response. Norepinephrine-induced IP2 formation was less sensitive to manganese than was formation of IP or IP3. These data suggest that either veratrine and norepinephrine cause hydrolysis of different pools of phosphoinositide or that the hydrolysis occurs by different mechanisms. The data also suggest that IP and IP2 may be produced directly from phosphatidylinositol and phosphatidylinositol 4-phosphate rather than solely as a metabolite of IP3.


The CNN model aided the study of the clinical value hidden in the implant images.
This article aims to construct a new method to evaluate radiographic image identification results based on artificial intelligence, which can complement the limited vision of researchers when studying the effect of various factors on clinical implantation outcomes. We constructed a convolutional neural network (CNN) model using the clinical implant radiographic images. Moreover, we used gradient-weighted class activation mapping (Grad-CAM) to obtain thermal maps to present identification differences before performing statistical analyses. Subsequently, to verify whether these differences presented by the Grad-CAM algorithm would be of value to clinical practices, we measured the bone thickness around the identified sites. Finally, we analyzed the influence of the implant type on the implantation according to the measurement results. The thermal maps showed that the sites with significant differences between Straumann BL and Bicon implants as identified by the CNN model were mainly the thread and neck area. (2) The heights of the mesial, distal, buccal, and lingual bone of the Bicon implant post-op were greater than those of Straumann BL (P < 0.05). (3) Between the first and second stages of surgery, the amount of bone thickness variation at the buccal and lingual sides of the Bicon implant platform was greater than that of the Straumann BL implant (P < 0.05). According to the results of this study, we found that the identified-neck-area of the Bicon implant was placed deeper than the Straumann BL implant, and there was more bone resorption on the buccal and lingual sides at the Bicon implant platform between the first and second stages of surgery. In summary, this study proves that using the CNN classification model can identify differences that complement our limited vision.


[Leishmaniasis diagnosis: going from microscopic observation of parasite to DNA detection].
Leishmaniasis is a disease caused by several species from Leishmania genus, which has been increasingly reported in the last few years. Several genetic, immunological factors and others related to this parasite have been associated to the outcome of the infection, and the occurrence of illness in varied clinical forms. All the aforementioned has an impact on the diagnostic method that should be used. A basic and recent literature review was made, mainly focused on general aspects of leishmaniasis as epidemiological situation of disease, life cycle and transmission, vectors, clinical presentation and diagnosis; the latter shows information about the main methods used at present. The procedure followed by the Leishmania group at "Pedro Kourí" Institute of Tropical Medicine to support the diagnostic activities was presented as well. Updated practical information about the chosen topics was presented, with a practical guiding approach aimed at the health personnel that must face suspected leishmaniasis cases. Tables and figures summarized relevant aspects in an organized form, as well as the working algorithm of Institute concerning diagnosis was presented. The application of molecular diagnosis by this working team was particularly underlined. As leishmaniasis is still out of control, opportune diagnosis remains a must. All the methods provide useful information for taking decisions on clinical management, treatment and epidemiology of this parasitosis; hence, a working algorithm was submitted in our lab based on the most useful methods under our present conditions and experience.


Cl@Si20X20 cages: evaluation of encapsulation nature, structural rigidity, and 29Si-NMR patterns using relativistic DFT calculations.
The experimental characterization of Cl@Si20 endohedral clusters, featuring different ligands such as [Cl@Si20H20]- (1) [Cl@Si20H12Cl8]- (2), and [Cl@Si20Cl20]- (3), provides insight into the variable encapsulation environment for chloride anions. The favorable formation of such species enables the evaluation of the encapsulation nature and the role of the inner anion in the rigidity of the overall cluster. Our results show a sizable interaction which increases as -66.7, -100.8, and -130.3 kcal mol-1 from 1 to 3, respectively, featuring electrostatic character. The orbital interaction involves 3p-Cl → Si20X20 and 3s-Cl → Si20X20 charge transfer channels and a slight contribution from London dispersion-type interactions. These results show that the inner bonding environment can be modified by the choice of exobonded ligands. Moreover, 29Si-NMR parameters are depicted in terms of the chemical shift anisotropy (CSA), leading to a strong variation of the three principal tensor components (δ11, δ22, δ33), unraveling the origin of the experimental 29Si-NMR chemical shift (δiso) differences along the given series. Thus, the Si20 cage is a useful template to further evaluate different environments for encapsulating atomic species.


LCTree-Based Approach for Mining Frequent Items in Real-Time.
With the increase of real-time stream data, knowledge discovery from stream data becomes more and more important, which requires an efficient data structure to store transactions and scan sliding windows once to discover frequent itemsets. We present a new method named Linking Compact Tree (LCTree). We designed an algorithm by using an improved data structure to create objective tree, which can find frequent itemsets with linear complexity. Secondly, we can merge items in sliding windows by one scan with Head Linking List data structure. Third, by implementing data structure of Tail Linking List, we can locate the obsolete nodes and remove them easily. Finally, LCTree is able to find all exact frequent items in data stream with reduced time and space complexity by using such a linear data structure. Experiments on datasets with different sizes and types were conducted to compare the proposed LCTree technique with well-known frequent item mining methods including Cantree, FP-tree, DSTree, CPSTree, and Gtree. The results of experiments show presented algorithm has better performance than other methods, and also confirm that it is a promising solution for detecting frequent item sets in real time applications.


Factor structure and invariance test of the alcohol use disorder identification test (AUDIT): Comparison and further validation in a U.S. and Philippines college student sample.
The Alcohol Use Disorder Identification Test's factor structure varies depending on population and culture. Because of this inconsistency, this article examined the factor structure of the test and conducted a factorial invariance test between a U.S. and a Philippines college sample. Confirmatory factor analyses indicated that a three-factor solution outperforms the one- and two-factor solution in both samples. Factorial invariance analyses further supports the confirmatory findings by showing that factor loadings were generally invariant across groups; however, item intercepts show non-invariance. Country differences between factors show that Filipino consumption factor mean scores were significantly lower than their U.S. counterparts.


Aggregation of silver nanoplates in the presence of L-cysteine and the application for separation.
A facile method was investigated to fabricate the aggregated silver nanoplates as products for separation materials. Initially, ageing of L-cysteine capped silver nanoplates in ethanol solvent led to fast aggregation. Then, the as-formed aggregates were easily prepared as powder due to the highly volatile properties of ethanol. Interestingly, the aggregated powder would be soluble again after the dispersion in water and the re-dispersed nanoplates could be obtained. Furthermore, the heavy metal ions such as Cu2+, Pb2+ and Hg2+ would soon accelerate the aggregation of the dispersed silver nanoplates again. The reversible aggregation process could be employed for separation applications in the future.


Association between levobupivacaine and pancuronium. Interference in neuromuscular transmission and blockade in rats.
To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro. Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP). Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs. Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.


Sequential reactions with Grubbs catalyst and AD-mix-alpha/beta using PDMS thimbles.
Incompatible Grubbs catalyst and an osmium dihydroxylation catalyst were site-isolated from each other using polydimethylsiloxane thimbles. The Grubbs catalyst was added to the interior of the thimbles, and AD-mix-alpha/beta was added to the exterior. Organic substrates readily fluxed through the walls of the thimbles and reacted with each catalyst. A series of cascade reactions were developed including those with intermediates possessing low boiling points or that were foul smelling.


Guidelines for the management and treatment of periodic fever syndromes familial Mediterranean fever.
To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints. 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene. 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment. 4. The therapy of choice is colchicine; this drug has proven its effectiveness in preventing acute inflammatory episodes and progression toward amyloidosis in adults. 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.


Controlled Growth of Vertically Aligned Nanocomposites through a Au Seeding-Assisted Method.
Heteroepitaxial metal-oxide vertically aligned nanocomposites (VAN) have piqued significant interest due to their remarkable vertical interfacial coupling effects, strong structural and property anisotropy, and potential applications in magnetoelectrics, photocatalysts, and optical metamaterials. VANs present a unique pillar-in-matrix structure with uniform but rather random pillar distributions. Achieving a well-controlled pillar growth remains a major challenge in this field. Here, we use BaTiO3 (BTO)-Au as a model VAN system to demonstrate the effects of Au seedings on achieving such pillar-growth control with enhanced ordering and morphology tuning. The Au seedings are introduced using an anodic aluminum oxide (AAO) template through pulsed laser deposition (PLD). TEM characterization reveals that the Au seedings result in straighter and more evenly distributed Au pillars in the BTO matrix compared to those without seeding, with the diameter of the Au seedings increasing with the number of pulses. Additionally, spectroscopic ellipsometry demonstrates distinct permittivity dispersion for all samples. This demonstration lays a foundation for future controlled and selective growth of VAN systems for on-chip integration.


A Systematic Review of Qualitative Research Literature and a Thematic Synthesis of Older LGBTQ People's Experiences of Quality of Life, Minority Joy, Resilience, Minority Stress, Discrimination, and Stigmatization in Japan and Sweden.
There is a lack of research on older lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) adults. This systematic review aimed to synthesize Japanese and Swedish qualitative research on LGBTQ adults aged 60 years or older following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Japanese and Swedish articles, published in English, were searched across ASSIA, CINAHL, Medline, PsychINFO, PubMed, Scopus, and Sociological Abstracts databases. Additional searches were conducted to include studies in Japanese or Swedish. There were no papers from Japan, whereas five from Sweden were reviewed. One article was excluded due to the wrong phenomenon. Four articles were included, involving 48 participants aged 60-94 years. We summarized the findings using a deductive thematic synthesis. Two major themes emerged: (a) quality of life, minority joy, and resilience (positive aspects), and (b) discrimination, stigmatization, and minority stress (negative aspects). The participants wished to be acknowledged for their own assets and unique life histories, and to be treated as everyone else. They emphasized the importance of knowledge of LGBTQ issues among nursing staff, so that older LGBTQ people are treated in a competent and affirmative way. The study revealed several important topics for understanding older LGBTQ adults' life circumstances and the severe lack of qualitative studies in Japan and Sweden.


Scientific rationale for management of diabetes in pregnancy. Recent approaches with innovative computer-based technology.
A series of recent studies in women with gestational diabetes mellitus is reviewed. During the studies, which were designed to gain a better understanding of the etiology of perinatal morbidity, a novel means of collecting ambulatory blood glucose values was employed. Subjects used specially modified reflectance meters with onboard memories to record each value with corresponding time and date. The data were transmitted to a microcomputer and rapidly analyzed to permit effective follow-up in the study population. The system enabled the investigators to characterize metabolic control, evaluate different treatment modalities, and measure the association between glycemic control and fetal outcome. These studies indicate that patients with one elevated blood glucose value during formal glucose tolerance testings have higher blood glucose values under ambulatory conditions. Furthermore, these elevated ambulatory glucose values were significantly correlated with fetal macrosomia. Treatment regimens designed to lower verified ambulatory blood glucose measurements may help reduce fetal macrosomia in women with milder forms of gestational diabetes or in women with relative glucose intolerance without a substantial increase in severe hypoglycemia.


Application of functionalized lanthanide-based nanoparticles for the detection of okadaic acid-specific immunoglobulin G.
Marine biotoxins are widespread in the environment and impact human health via contaminated shellfish, causing diarrhetic, amnesic, paralytic, or neurotoxic poisoning. In spite of this, methods for determining if poisoning has occurred are limited. We show the development of a simple and sensitive luminescence resonance energy transfer (LRET)-based concept which allows the detection of anti-okadaic acid rabbit polyclonal IgG (mouse monoclonal IgG1) using functionalized lanthanide-based nanoparticles. Upon UV excitation, the functionalized nanoparticles were shown to undergo LRET with fluorophore-labeled anti-okadaic acid antibodies which had been captured and bound by okadaic acid-decorated nanoparticles. The linear dependence of fluorescence emission intensity with antigen-antibody binding events was recorded in the nanomolar to micromolar range, while essentially no LRET signal was detected in the absence of antibody. These results may find applications in new, cheap, and robust sensors for detecting not only immune responses to biotoxins but also a wide range of biomolecules based on antigen-antibody recognition systems. Further, as the system is based on solution chemistry it may be sufficiently simple and versatile to be applied at point-of-care.


Utilization of computer processed high definition video imaging for measuring motility of microscopic nematode stages on a quantitative scale: "The Worminator".
A major hindrance to evaluating nematode populations for anthelmintic resistance, as well as for screening existing drugs, new compounds, or bioactive plant extracts for anthelmintic properties, is the lack of an efficient, objective, and reproducible in vitro assay that is adaptable to multiple life stages and parasite genera. To address this need we have developed the "Worminator" system, which objectively and quantitatively measures the motility of microscopic stages of parasitic nematodes. The system is built around the computer application "WormAssay", developed at the Center for Discovery and Innovation in Parasitic Diseases at the University of California, San Francisco. WormAssay was designed to assess motility of macroscopic parasites for the purpose of high throughput screening of potential anthelmintic compounds, utilizing high definition video as an input to assess motion of adult stage (macroscopic) parasites (e.g. Brugia malayi). We adapted this assay for use with microscopic parasites by modifying the software to support a full frame analysis mode that applies the motion algorithm to the entire video frame. Thus, the motility of all parasites in a given well are recorded and measured simultaneously. Assays performed on third-stage larvae (L3) of the bovine intestinal nematode Cooperia spp., as well as microfilariae (mf) of the filarioid nematodes B. malayi and Dirofilaria immitis, yielded reproducible dose responses using the macrocyclic lactones ivermectin, doramectin, and moxidectin, as well as the nicotinic agonists, pyrantel, oxantel, morantel, and tribendimidine. This new computer based-assay is simple to use, requires minimal new investment in equipment, is robust across nematode genera and developmental stage, and does not require subjective scoring of motility by an observer. Thus, the "Worminator" provides a relatively low-cost platform for developing genera- and stage-specific assays with high efficiency and reproducibility, low labor input, and yields objective motility data that is not subject to scorer bias.


Acute myocarditis after massive phenelzine overdose.
Monoamine oxidase inhibitors (MAOIs) are uncommonly used due to their high frequency of adverse effects, including tachycardia and hypertension. Recently, there has been renewed interest in the role of this class of drugs in treating a variety of psychiatric disorders. The clinical features of MAOI overdose are poorly characterised. This paper describes a novel cardiac complication of phenelzine toxicity in a previously healthy young adult with no history of cardiovascular disease. A 23-year-old woman presented to hospital after massive phenelzine overdose, and the clinical features and pathological findings are discussed in light of existing literature. Clinical features of phenelzine toxicity included reduced consciousness level, seizures, and tachycardia, in keeping with previous reports. Unexpectedly, the patient developed severe and unexplained hypotension and impaired left ventricular function, and died 3 days after initial presentation. Post-mortem examination confirmed high serum phenelzine concentrations (4.1 mg/L) and histopathological features that were consistent with drug-induced acute myocarditis. Acute myocarditis was attributed to phenelzine in the absence of any plausible alternative explanation. This possible complication should be considered in patients who develop unexplained hypotension after phenelzine overdose.


Antiproliferative, Apoptotic, and Autophagic Activity of Ranibizumab, Bevacizumab, Pegaptanib, and Aflibercept on Fibroblasts: Implication for Choroidal Neovascularization.
Purpose. Choroidal neovascularization (CNV) is one of the most common complications of retinal diseases accompanied by elevated secretion of vascular endothelial growth factor (VEGF). Intravitreal anti-VEGFs (ranibizumab, bevacizumab, pegaptanib, and aflibercept) can suppress neovascularization, decrease vascular permeability and CNV size, and, thereby, improve visual function. The antiproliferative, apoptotic, and autophagic effect of anti-VEGF drugs on fibroblasts found in CNVs has not been yet explored. Methods. Concentration-dependent cellular effects of the four anti-VEGFs were examined in L929 fibroblasts over a 5-day period. The cell survival, mitotic and polykaryocytic indices, the level of apoptosis and autophagy, and the cellular growth kinetics were all assessed. Results. The anti-VEGFs could inhibit the survival, mitotic activity, and proliferation as well as increase the cellular heterogeneity, apoptosis, and autophagy of the fibroblasts in a dose-dependent manner. Cellular growth kinetics showed ranibizumab to be less aggressive, but three other anti-VEGFs showed higher antiproliferative and apoptotic activity and expressed negative cellular growth kinetics. Conclusions. The antiproliferative, apoptotic, and autophagic activity of anti-VEGFs upon fibroblasts may explain the cellular response and the etiology of CNV involution in vivo and serve as a good study model for CNV in vitro.


Azelnidipine, Not Amlodipine, Induces Secretion of Vascular Endothelial Growth Factor From Smooth Muscle Cells and Promotes Endothelial Tube Formation.
We previously reported that the calcium channel blocker (CCB) nifedipine-induced secretion of vascular endothelial growth factor (VEGF) from human coronary smooth muscle cells (HCSMCs) promoted human coronary endothelial cell (HCEC) tube formation. Therefore, we analyzed whether other CCBs, azelnidipine and amlodipine, also induced the secretion of VEGF and promoted HCEC tube formation, and the underlying molecular mechanisms. To evaluate the tube formation, HCECs were grown on Matrigel for 18 hours in the supernatants from HCSMCs that had been treated with different kinds of reagents. Concentrations of VEGF in cultured HCSMCs were determined by specific enzyme immunoassays. Nuclear extracts from HCSMCs were prepared, and nuclear factor-kappa B (NF-κB) activation was measured by EZ-DetectTM Transcription Factor Kits for NF-κB p50 or p65. Although azelnidipine dose-dependently stimulated the significant secretion of VEGF from HCSMCs and this stimulation was abolished by a protein kinase C inhibitor, amlodipine-induced secretion of VEGF was significantly lower than that induced by azelnidipine. The medium derived from azelnidipine (at up to 2 μM)-treated HCSMCs led to HCEC tube formation, whereas that obtained with amlodipine did not. Azelnidipine-induced tube formation was blocked by an inhibitor of kinase insert domain-containing receptor/fetal liver kinase-1 tyrosine kinase. Azelnidipine at up to 2 μM induced NF-κB activation. Azelnidipine, but not amlodipine, stimulated the secretion of VEGF from HCSMCs and induced HCEC tube formation. This secretion is mediated at least in part via the activation of NF-κB. Azelnidipine may have a novel beneficial effect in improving coronary microvascular blood flow in addition to its main effect of lowering blood pressure.


Interpenetration of a 3D Icosahedral M@Ni12 (M=Al, Ga) Framework with Porphyrin-Reminiscent Boron Layers in MNi9 B8.
Two ternary borides MNi9 B8 (M=Al, Ga) were synthesized by thermal treatment of mixtures of the elements. Single-crystal X-ray diffraction data reveal AlNi9 B8 and GaNi9 B8 crystallizing in a new type of structure within the space group Cmcm and the lattice parameters a=7.0896(3) Å, b=8.1181(3) Å, c=10.6497(4) Å and a=7.0897(5) Å, b=8.1579(4) Å, c=10.6648(7) Å, respectively. The boron atoms build up two-dimensional layers, which consist of puckered [B16 ] rings with two tailing B atoms, whereas the M atoms reside in distorted vertices-condensed [Ni12 ] icosahedra, which form a three-dimensional framework interpenetrated by boron porphyrin-reminiscent layers. An unusual local arrangement resembling a giant metallo-porphyrin entity is formed by the [B16 ] rings, which, due to their large annular size of approximately 8 Å, chelate four of the twelve icosahedral Ni atoms. An analysis of the chemical bonding by means of the electron localizability approach reveals strong covalent B-B interactions and weak Ni-Ni interactions. Multi-center dative B-Ni interaction occurs between the Al-Ni framework and the boron layers. In agreement with the chemical bonding analysis and band structure calculations, AlNi9 B8 is a Pauli-paramagnetic metal.


Closing the gaps in the continuum of depression care for persons with HIV: modeling the impact on viral suppression in the United States.
Depression is prevalent among persons with HIV (PWH) and is associated with poorer adherence and lack of viral load suppression (VLS). When treated for depression, PWH are more likely to stay in HIV care and adhere to medications; however, for many PWH, depression is not adequately diagnosed or treated. We adapted Progression and Transmission of HIV (PATH 3.0), a U.S. agent-based dynamic stochastic simulation model, by incorporating a continuum of depression care and estimating the impact on VLS of an enhanced depression diagnosis and care scenario (EDC). We compared EDC - whereby every PWH is assessed for depression, gets treatment if diagnosed, and of those, half achieve remission - to a status quo scenario (SQ) on VLS. Based on published findings, assumptions for SQ were: 34.7% depressed, 45% diagnosed, 55.3% treated and 33% of treated achieving remission. Compared to PWH without depression, we assumed the probability of being non-virally suppressed increased by 1.57 times for PWH with depression (PWH-D), and by 0.95 times for PWH with remitted depression. There was an average increase of 14.6% (11.5-18.5) in the proportion of PWH-D who achieved VLS in EDC compared to SQ. Among all PWH, there was a 4.7% (3.4-6.0) increase in the proportion who achieved VLS in EDC compared to SQ. Fully diagnosing and adequately treating depression would improve health and quality of life for a substantial proportion of PWH-D and result in a nearly 5% increase in expected rates of VLS in the United States, supporting national prevention goals.


Clinical and Cognitive Characteristics Associated with Mathematics Problem Solving in Adolescents with Autism Spectrum Disorder.
Mathematics achievement in autism spectrum disorder (ASD) has been understudied. However, the ability to solve applied math problems is associated with academic achievement, everyday problem-solving abilities, and vocational outcomes. The paucity of research on math achievement in ASD may be partly explained by the widely-held belief that most individuals with ASD are mathematically gifted, despite emerging evidence to the contrary. The purpose of the study was twofold: to assess the relative proportions of youth with ASD who demonstrate giftedness versus disability on applied math problems, and to examine which cognitive (i.e., perceptual reasoning, verbal ability, working memory) and clinical (i.e., test anxiety) characteristics best predict achievement on applied math problems in ASD relative to typically developing peers. Twenty-seven high-functioning adolescents with ASD and 27 age- and Full Scale IQ-matched typically developing controls were assessed on standardized measures of math problem solving, perceptual reasoning, verbal ability, and test anxiety. Results indicated that 22% of the ASD sample evidenced a mathematics learning disability, while only 4% exhibited mathematical giftedness. The parsimonious linear regression model revealed that the strongest predictor of math problem solving was perceptual reasoning, followed by verbal ability and test anxiety, then diagnosis of ASD. These results inform our theories of math ability in ASD and highlight possible targets of intervention for students with ASD struggling with mathematics.


Enhanced oligodendrogenesis and recovery of neurological function by erythropoietin after neonatal hypoxic/ischemic brain injury.
Neuronal replacement has recently gained attention as a potential therapeutic target under ischemic conditions. However, the oligodendrogenic infrastructure is equally critical for restoration of brain function and is also sensitive to ischemic injury. Erythropoietin (EPO) is a neuroprotective molecule that stimulates neuronal replacement after neonatal hypoxia/ischemia (H/I) when delivered soon after the onset of reperfusion. Because EPO can improve recovery of neurological function in the absence of tissue protection, we hypothesize that EPO may improve neurological function via enhancement of white matter recovery after H/I. Thus, we sought to determine the effects of delayed administration of EPO on white matter injury and recovery of neurological function after neonatal H/I. EPO (1000 U/kg) was injected intraperitoneally at multiple time points beginning 48 hours after H/I in postnatal day 7 rats. The effects of EPO on oligodendrogenesis, white matter injury, and neurogenesis were evaluated using bromodeoxyuridine incorporation and cell-specific immunohistochemistry. Neurological function was assessed by sensorimotor behavioral tests. Delayed administration of EPO was incapable of reducing brain volume loss but significantly increased oligodendrogenesis and maturation of oligodendrocytes and attenuated white matter injury after H/I. These effects occurred concurrently with enhanced neurogenesis. Delayed EPO treatment improved behavioral neurological outcomes 14 days after H/I injury. Our study demonstrates that delayed administration of EPO promotes oligodendrogenesis and attenuates white matter injury concurrently with increased neurogenesis. These effects likely contribute to the observed improvement in neurological functional outcomes.


Previous exposure to simulated microgravity does not exacerbate bone loss during subsequent exposure in the proximal tibia of adult rats.
Extended periods of inactivity cause severe bone loss and concomitant deterioration of the musculoskeletal system. Considerable research has been aimed at better understanding the mechanisms and consequences of bone loss due to unloading and the associated effects on strength and fracture risk. One factor that has not been studied extensively but is of great interest, particularly for human spaceflight, is how multiple or repeated exposures to unloading and reloading affect the skeleton. Space agencies worldwide anticipate increased usage of repeat-flier crewmembers, and major thrust of research has focused on better understanding of microgravity effects on loss of bone density at weightbearing skeletal sites; however there is limited data available on repeat microgravity exposure. The adult hindlimb unloaded (HU) rat model was used to determine how an initial unloading cycle will affect a subsequent exposure to disuse and recovery thereafter. Animals underwent 28 days of HU starting at 6 months of age followed by 56 days of recovery, and then another 28 days of HU with 56 days of recovery. In vivo longitudinal pQCT was used to quantify bone morphological changes, and ex vivo μCT was used to quantify trabecular microarchitecture and cortical shell geometry at the proximal tibia metaphysis (PTM). The mechanical properties of trabecular bone were examined by the reduced platen compression mechanical test. The hypothesis that the initial HU exposure will mitigate decrements in bone mass and density for the second HU exposure was supported as pre- to post-HU declines in total BMC, total vBMD, and cortical area by in vivo pQCT at the proximal tibia metaphysis were milder for the second HU (and not significant) compared to an age-matched single HU (3% vs. 6%, 2% vs. 6%, and 2% vs. 6%, respectively). In contrast, the hypothesis was not supported at the microarchitectural level as losses in BV/TV and Tb.Th. were similar during 2nd HU exposure and age-matched single HU. Recovery with respect to post-HU values and compared to aging controls for total BMC, vBMD and cortical area were slower in older animals exposed to single or double HU cycles compared to recovery of younger animals exposed to a single HU bout. Despite milder recovery at the older age, there was no difference between unloaded animals and controls at the end of second recovery period. Therefore, the data did not support the hypothesis that two cycles of HU exposure with recovery would have a net negative effect. Mechanical properties of trabecular bone were affected more severely than densitometric measures (35% loss in trabecular bone ultimate stress vs. 9% loss in trabecular vBMD), which can be attributed most prominently to reductions in trabecular bone density and tissue mineral density. Together, our data demonstrate that initial exposure to mechanical unloading does not exacerbate bone loss during a subsequent unloading period and two cycles of unloading followed by recovery do not have a cumulative net negative effect on total bone mineral content and density as measured by pQCT at the proximal tibia metaphysis.


Corticobasal ganglionic degeneration and progressive supranuclear palsy presenting with cognitive decline.
Corticobasal ganglionic degeneration (CBGD) and progressive supranuclear palsy (PSP) were originally described in the sixties as predominantly motor syndromes. Over the years, the detailed study of additional cases of CBGD has shown that it is a distinctive histological entity which can often present as dementia or aphasia. Although some pathological features of CBGD overlap with those of other forms of non-Alzheimer non-Lewy body dementia, the distribution and relative number of these abnormalities and the distinctive pattern of tau immunodeposits allows the distinction of CBGD from Pick's disease and fronto-temporal dementia. In contrast, PSP only rarely presents with prominent dementia or behavioral changes. In these unusual PSP cases, care must be taken to exclude the diagnoses of CBGD and familial tangle-only dementia.


WAFER-SCALE, SOLID FREEFORM FABRICATION OF FULLY-ASSEMBLED METAL MICRO-MECHANISMS FOR MINIMALLY-INVASIVE MEDICAL DEVICES.
The EFAB process was first presented at the SFF Symposium in 1998, at a very early stage of its development. Currently, the technology is able to produce complex 3-D devices-including mechanisms built pre-assembled-in production volumes, using a three-step process of selective electrodeposition of one metal, blanket electrodeposition of another metal, and planarization. Layer thickness is as small as 4 μm, minimum feature size is down to 10 μm, and linear tolerances are ~2 μm. Metals are biocompatible materials with mechanical properties similar to stainless steel. The technology enables new instruments for minimally-invasive surgical and interventional procedures.