[Adult intestinal no rotation].
90% of cases of intestinal obstruction caused by intestinal malrotation occur in children under 1 year of age, being very uncommon in adults. A female patient of 27 years of age consults with abdominal pain, vomiting, abdominal distention, dehydration and signs of severe malnutrition. After EGDS, CT scan, and 48 hours of clinical expectation, surgical intervention was decided with diagnosis of high intestinal obstruction. Intraoperative finding was no intestinal rotation at all. Ladd´s technique was performed together with prophylactic appendectomy. Postoperative evolution was favorable. The rare presentation in adults motivates the presentation of this case.


Evidence-Based Medicine for Midface/Orbit/Upper Facial Fracture Repair.
The face is one of the most common areas of traumatic injury, making up approximately 25% of all injuries in 2016. Assault, motor vehicle collision (MVC), fall, sports, occupational, and gunshot wounds (GSW) are all common causes of facial fractures, with MVC and GSW leading to significantly higher severity of injuries. Most facial fractures occur in the upper two-thirds of the face. Most facial fractures require timely assessment, diagnosis, and treatment for optimal restoration of facial structures and functions. Without proper initial management, significant complications including immediate complications such as airway compromise, massive bleeding, infection, intracranial hemorrhages, or even death, and long-term complications such as poor functional outcomes and aesthetic setbacks can occur. The goal of this review is to summarize the management of fractures of the upper face, orbit, and midface and provide an update about complications and their management.


A discussion of blood cancers and the MPN landmark survey.
Professor Claire Harrison speaks to Roshaine Wijayatunga, managing commissioning editor: Professor Claire Harrison became a consultant at Guy's and St Thomas' hospital in 2001. She is also deputy clinical director of cancer and hematology. She has influenced major advances in her field, including the description of key mutations and designing/leading global clinical trials, for example, the first JAK inhibitor trial in Europe. She is the chief investigator for several other international and national clinical trials. She has strong international collaborations and authors many papers in peer-reviewed journals such as the New England Journal of Medicine and Blood. She has worked with enthusiastic patients to create a patient charity, MPN Voice. She is an internationally regarded expert in her field as a patient advocate.


[Thinking on methodologies and problems existed in clinical study of acupuncture and moxibustion].
The modernization and internationalization of acupuncture and moxibustion is inevitable trends to develop acupuncture and moxibustion. However, the acupuncture research findings in China are not accepted by the mainstream medicine abroad. The major problems are that the study purposes are not specific and the modern scientific research methods are not rationally used in acupuncture clinical study. Two major issues in acupuncture clinical study in China are the evaluation of the specificity of acupuncture and the overall effect of acupuncture treatment. The core and basis of acupuncture clinical study are the clarity of study purpose, following the law of evidence-based medicine and rational selection of modern scientific methods. On the basis of the characteristics of acupuncture and the specialty of acupuncture clinical study, for instance, the types of trial design, blind methods, the selection of control group and outcome assessment system, the objective of this paper provides research strategies for researchers and to improve the overall level of research in the acupuncture clinical study.


Knockdown of miR-182 promotes apoptosis via regulating RIP1 deubiquitination in TNF-α-treated triple-negative breast cancer cells.
Overexpression of microRNA-182 (miR-182) is found in multiple cancers, but the association of miR-182 expression with the sensitivity of triple-negative breast cancer (TNBC) cells to tumor necrosis factor-alpha (TNF-α) remains unknown. In this study, up-regulation of miR-182 was validated in TNBC patients and cell lines. Knockdown of miR-182 was observed to hinder the proliferation of BT-549 cells. More importantly, knockdown of miR-182 significantly promoted the apoptosis induced by TNF-α treatment in BT-549. JC-1 staining and western blot assays revealed that the K63-linked ubiquitin chains on receptor-interacting protein 1 (RIP1) were removed and the outer mitochondrial membrane potential (MMP) and permeability was altered upon combination of TNF-α with anti-miR-182. We then demonstrated that knockdown of miR-182 up-regulated the expression of cylindromatosis (CYLD) deubiquitinase, which promoted the formation of death-inducing signaling complex (DISC) and subsequent caspase-8 activation in TNF-α-treated BT-549 cells. Collectively, the results of the present study improve our understanding of the role of miR-182 in TNBC, knockdown of which facilitates the degradation of ubiquitin chains on RIP1, leading to the caspase-8 activation and apoptosis in TNF-α-treated TNBC cells. This may be valuable for the development of cancer therapy.


Microvascular abnormalities in patients with rheumatoid arthritis.
Microvascular involvement represents one of the first apparent steps in many autoimmune diseases such as rheumatoid arthritis (RA). Early in the disease, peripheral microangiopathy may be easily recognized and studied by videocapillaroscopy. The aim of this study has been to observe the differences in labial microcirculation between healthy patients and patients suffering from RA. A total of 30 healthy patients and 30 patients suffering from RA were examined. The patients with conditions known to compromise microcirculation, such as diabetes, hypertension, or some pharmacological treatments were not included in the study. All the patients were non-smokers. Labial capillaroscopy was used to investigate the characteristics of microcirculation. Visibility, course, tortuosity, as well as the possible presence of microhemorrhages, the average caliber of the capillary loops and the number of visible capillary loops per square millimeter were evaluated for each patient. The investigation was simple, non-invasive, and repeatable for each patient. In patients suffering from RA, it was possible to observe a reduced caliber of capillaries, as well as greater elongated capillaries, in comparison to controls. This study shows that capillary alterations in patients suffering from RA occur in labial mucosa microcirculation; such evidence could be extremely important in the diagnosis of suspected RA.


Developing Versatile Contactors for Direct Air Capture of CO2 through Amine Grafting onto Alumina Pellets and Alumina Wash-Coated Monoliths.
The optimization of the air-solid contactor is critical to improve the efficiency of the direct air capture (DAC) process. To enable comparison of contactors and therefore a step toward optimization, two contactors are prepared in the form of pellets and wash-coated honeycomb monoliths. The desired amine functionalities are successfully incorporated onto these industrially relevant pellets by means of a procedure developed for powders, providing materials with a CO2 uptake not influenced by the morphology and the structure of the materials according to the sorption measurements. Furthermore, the amine functionalities are incorporated onto alumina wash-coated monoliths that provide a similar CO2 uptake compared to the pellets. Using breakthrough measurements, dry CO2 uptakes of 0.44 and 0.4 mmol gsorbent-1 are measured for pellets and for a monolith, respectively. NMR and IR studies of CO2 uptake show that the CO2 adsorbs mainly in the form of ammonium carbamate. Both contactors are characterized by estimated Toth isotherm parameters and linear driving force (LDF) coefficients to enable an initial comparison and provide information for further studies of the two contactors. LDF coefficients of 1.5 × 10-4 and of 1.2 × 10-3 s-1 are estimated for the pellets and for a monolith, respectively. In comparison to the pellets, the monolith therefore exhibits particularly promising results in terms of adsorption kinetics due to its hierarchical pore structure. This is reflected in the productivity of the adsorption step of 6.48 mol m-3 h-1 for the pellets compared to 7.56 mol m-3 h-1 for the monolith at a pressure drop approximately 1 order of magnitude lower, making the monoliths prime candidates to enhance the efficiency of DAC processes.


Changes in perceived knowledge about childbirth among pregnant women participating in the Senses of Birth intervention in Brazil: a cross-sectional study.
Senses of Birth (SoB) is a health education intervention in Brazil that aims to reduce unnecessary cesareans in the country by providing information on reproductive rights, benefits and risks of childbirth, and use of intrapartum evidence-based practices (EBP) which are recommended by the World Health Organization (WHO) to improve childbirth outcomes and satisfaction. This study evaluates the impact of the SoB on pregnant women's perceived knowledge about normal birth (NB), cesarean, and use of EBP. 1287 pregnant women answered a structured survey immediately after their visit to the intervention, between March 2015 and March 2016. To estimate the potential impact of the intervention on women's perceived knowledge, and possible associations between sociodemographic characteristics and perceived knowledge, statistical analyses were performed, including paired T-tests, ANOVA, and logistic and linear regressions. The mean score (MS) of perceived knowledge after the intervention was higher than the MS before experiencing the intervention for all three knowledge domains: Normal Birth (MS Before = 3.71 x MS After = 4.49), Cesarean (MS Before = 3.54 x MS After = 4.26) and EBPs (MS Before = 3.14 x MS After = 4.14). The results suggest that perceived knowledge increased more for low-income women (B = 0.206; p < 0.001 for EBP), women without private health insurance (OR 2.47, 95% CI: 1.49-4.09 for NB), with private prenatal care (OR 2.42, 95% CI: 1.59-3.66 for NB), experiencing their first pregnancy (OR 1.92, 95% CI: 1.31-2.82 for EBP; OR 1.37, 95% CI: 1.03-1.84 for NB; OR 1.37, 95% CI: 1.03-1.84 for cesarean), and in their first or second trimester (OR 1.64, 95% CI: 1.13-2.39 for EBP; OR 1.48, 95% CI: 1.11-1.97 for NB; OR 1.85, 95% CI: 1.40-2.41 for cesarean). The study showed that participation in the SoB was associated with an increase in perceived knowledge among Brazilian pregnant women. The intervention gains relevance considering the lack of evidence of the impact of non-clinical interventions to reduce unnecessary cesareans in middle and low-income countries.


Occult pneumothoraces truly occult or simply missed: redux.
As utilization of computed tomography (CT) scans in the evaluation of trauma patients increases, pneumothoraces (PTXs) seen on CT but not on chest X-ray (CXR), known as occult PTXs (OPTXs), are becoming more prevalent. The incidence of PTXs simply missed on CXR among OPTXs is unclear. A previous retrospective review of CXRs at our institution generally confirmed the occult versus missed designation, but lower fidelity images may have biased this determination. Thus, we repeated this evaluation using the high-quality images and improved the methodology. The 70 Digital Imaging and Communications in Medicine (DICOM)-quality CXR images were randomly selected from two prospectively collected trauma databases including 22 normal, 5 overt PTX, and 43 study OPTX images. All CXR images were corroborated with multidetector CT imaging. Two blinded fellowship-trained radiologists reviewed and evaluated all the images on an IMPAX viewer. All images were deemed "adequate" except for one CXR by a single reviewer. For PTX diagnosis, agreement was 60% for overt PTXs, 86% for normal CXRs, and 81% for study OPTXs, yielding a kappa statistic of 0.51 (95% confidence interval, 0.22-0.81) indicating moderate agreement. Considering only the cases where the reviewers agreed, 80% of the study OPTXs were truly occult versus missed (95% confidence interval, 63-92%). In the 7 missed PTXs, subcutaneous emphysema (5), pleural line (3), and deep sulcus sign (2) were detected. We estimate that 80% of PTXs considered occult in the trauma room were truly occult. The most common missed sign was subcutaneous emphysema. PTXs are poorly assessed by CXR, and accurate diagnosis should focus on other imaging modalities.


Nonsteroidal anti-inflammatory drugs sensitize epithelial cells to Clostridioides difficile toxin-mediated mitochondrial damage.
Clostridioides difficile damages the colonic mucosa through the action of two potent exotoxins. Factors shaping C. difficile pathogenesis are incompletely understood but are likely due to the ecological factors in the gastrointestinal ecosystem, mucosal immune responses, and environmental factors. Little is known about the role of pharmaceutical drugs during C. difficile infection (CDI), but recent studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) worsen CDI. The mechanism underlying this phenomenon remains unclear. Here, we show that NSAIDs exacerbate CDI by disrupting colonic epithelial cells (CECs) and sensitizing cells to C. difficile toxin-mediated damage independent of their canonical role of inhibiting cyclooxygenase (COX) enzymes. Notably, we find that NSAIDs and C. difficile toxins target the mitochondria of CECs and enhance C. difficile toxin-mediated damage. Our results demonstrate that NSAIDs exacerbate CDI by synergizing with C. difficile toxins to damage host cell mitochondria. Together, this work highlights a role for NSAIDs in exacerbating microbial infection in the colon.


Lateral and feedforward inhibition suppress asynchronous activity in a large, biophysically-detailed computational model of the striatal network.
Striatal medium spiny neurons (MSNs) receive lateral inhibitory projections from other MSNs and feedforward inhibitory projections from fast-spiking, parvalbumin-containing striatal interneurons (FSIs). The functional roles of these connections are unknown, and difficult to study in an experimental preparation. We therefore investigated the functionality of both lateral (MSN-MSN) and feedforward (FSI-MSN) inhibition using a large-scale computational model of the striatal network. The model consists of 2744 MSNs comprised of 189 compartments each and 121 FSIs comprised of 148 compartments each, with dendrites explicitly represented and almost all known ionic currents included and strictly constrained by biological data as appropriate. Our analysis of the model indicates that both lateral inhibition and feedforward inhibition function at the population level to limit non-ensemble MSN spiking while preserving ensemble MSN spiking. Specifically, lateral inhibition enables large ensembles of MSNs firing synchronously to strongly suppress non-ensemble MSNs over a short time-scale (10-30 ms). Feedforward inhibition enables FSIs to strongly inhibit weakly activated, non-ensemble MSNs while moderately inhibiting activated ensemble MSNs. Importantly, FSIs appear to more effectively inhibit MSNs when FSIs fire asynchronously. Both types of inhibition would increase the signal-to-noise ratio of responding MSN ensembles and contribute to the formation and dissolution of MSN ensembles in the striatal network.


Evidence for spare nicotinic acetylcholine receptors and a beta 4 subunit in bovine adrenal chromaffin cells: studies using bromoacetylcholine, epibatidine, cytisine and mAb35.
Relatively little is known about the type and number of nicotinic acetylcholine receptors (nAChRs) that mediate secretion from adrenal chromaffin cells. In these studies, we investigated nAChR reserve pools and their modulation using bromoacetylcholine (brACh) and the anti-nAChR antibody mAb35. By using brACh under acetylating conditions, adrenal catecholamine release was reduced (IC50, approximately 0.3 microM). This effect was slowly reversible. Submaximal concentrations of brACh caused shifts to the right in concentration-response curves of approximately 4-fold, as well as decreases in Emax values for the agonists nicotine and epibatidine. Cytisine is a nAChR agonist (EC50, approximately 46 microM) that was somewhat less efficacious than nicotine (Emax, approximately 85% of 10 microM nicotine) in adrenal chromaffin cells. Submaximal concentrations of brACh caused a small shift to the right in the concentration-response curves for the agonist cytisine, as well as a decrease in the Emax value. mAb35, which causes a slowly developing loss of nAChR-mediated secretion, produced a time-dependent shift to the right in agonist concentration-response curves and a reduction in Emax for nicotine and epibatidine. mAb35 treatment produced only a reduction in the Emax value of cytisine. Finally, we cloned and sequenced a reverse transcription-polymerase chain reaction product from bovine adrenal chromaffin RNA that shares a high degree of homology with beta 4 nAChR subunits. Northern analysis provided evidence for the presence of this transcript in chromaffin cell cultures. Together, these studies support the presence of a nAChR reserve in adrenal chromaffin cells that is down-regulated by mAb35. These studies also support the presence of more than one nAChR population mediating secretion and the presence of beta 4 nAChR subunits.


Five dangers of materialism.
Amidst the boon of medical, scientific, and technological progress, materialism has gained increasing explanatory power in deciphering the enigma of mind. But with the proliferation and acceptance of cognitive science, psychic reality has been largely reduced to a physical ontology. In this article, the author explores the ground, scope, and limits to the materialist framework and shows that although biological-neurochemical physiology is a necessary condition for mental functioning, it is far from a sufficient condition to adequately explain the human being. This situation becomes especially significant when one examines the issues of selfhood, freedom, personal autonomy, and the phenomenal quality of the lived experience.


Pilot study of multi-gene pharmacogenetic testing for pain management in oncology palliative medicine.
Aim: We evaluated the application and clinical impact of multi-gene pharmacogenetic testing in oncology palliative medicine. Patients & methods: In a single-arm pilot trial, cancer patients with uncontrolled pain were assessed in a palliative medicine clinic at baseline and received pharmacogenetic testing. Results were used as applicable up to the final visit (day 30). Pain scores, opioid prescribing, and use of pharmacogenetic test results were collected. Results: In 75 patients, the median baseline pain score was 7/10. Of 54 evaluable at the final visit, 28 required opioid modifications and 19 had actionable genotypes, mostly CYP2D6. Pain improvement (≥2-point reduction) was higher than historical data (56 vs 30%; p < 0.001). There were no differences in pain improvement between those with and without actionable genotypes (61 vs 53%). Conclusion: Multi-gene testing identified actionable genotypes and may improve cancer pain.


Beyond open access: open discourse, the next great equalizer.
The internet is expanding the realm of scientific publishing to include free and open public debate of published papers. Journals are beginning to support web posting of comments on their published articles and independent organizations are providing centralized web sites for posting comments about any published article. The trend promises to give one and all access to read and contribute to cutting edge scientific criticism and debate.


Circularly permutated bioluminescent probes for illuminating ligand-activated protein dynamics.
Engineered bioluminescent enzymes provide a creative approach for illuminating the intracellular molecular events. We demonstrate a new strategy for molecular imaging of bioactive small molecules using circularly permutated luciferases (cpLuc), derived from Gaussia princeps (GLuc), Photinus pyralis (FLuc), and Pyrearinus termitilluminans (CBLuc): (i) the luciferases were first dissected into two fragments, (ii) the original N- and C-termini were linked with a GS linker and the new termini were created in an appropriate site, and (iii) the new ends were correspondingly linked with proteins of interest, e.g., a ligand-binding domain (LBD) and an LBD-recognition protein. When the ends of the cpCBLuc were linked with LBD of estrogen receptor (ER) and Src homology 2 domain of Src (SH2 of Src), the estrogen can trigger an intramolecular ER LBD-Src SH2 binding. This assembly subsequently provokes an approximation of the adjacent fragments of cpCBLuc recovering the enzyme activity. These probes were surprisingly stable in the mammalian cells and largely exhibited a decreased background luminescence (e.g., 1000 times in case of cpGLuc) and improved signal-to-noise ratios, compared with the non-CP indicators. This study offers a new strategy for luciferase-aided probing systems. Our study is the first to fabricate circular permutation (CP) in luciferases for tracing the molecular dynamics of proteins.


Evaluation of threshold response and appropriate electrode placement site for electric pulp testing in fluorosed anterior teeth: An in vivo study.
Accurate diagnosis is key to success. Diagnosing the pulpal status in varied clinical situations poses a challenge to the clinician. Electric pulp test (EPT) is one of the valuable attempts in evaluating the sensibility of pulp tissue. The aim of this study was to find out and compare the threshold levels and optimal electrode placement site for EPT in fluorosed and nonfluorosed anterior teeth. Eighty volunteers recruited for this study were divided into two groups based on the incidence of dental fluorosis. Electric pulp testing was done on either of the central incisors in fluorosed and nonfluorosed group. Four sites on each crown were tested 4 times with digitest electric pulp tester, and the mean of the threshold responses was recorded. The data were analyzed with SPSS, version 11. Means of variables from each location were compared using one-way ANOVA and Tukey's post-hoc test while the critical level of significance was set at P < 0.05. The mean and standard deviation of threshold levels in fluorosed teeth were greater when compared to that of nonfluorosed teeth at all sites with incisal edge showing the least mean threshold levels for both the groups (P > 0.05). Within the limitations of this study, it can be concluded that fluorosed teeth respond to higher threshold levels than the non-fluorosed teeth, and incisal edge was the optimal electrode placement site.


Techniques for estimating on-animal populations of Ctenocephalides felis (Siphonaptera: Pulicidae).
Effectiveness of two sampling techniques to estimate cat flea populations were compared on beagles (short-haired dogs). Overall, 23.5 and 81.6% of known flea populations on the beagles were detected using area and comb counting techniques, respectively. Using comb counts, we were able to differentiate among beagles that were infested experimentally to produce densities of 21.6 (low), 42.2 (medium), and 82.5 (high) fleas per dog. Using the area counting technique, we were able to differentiate between the medium and high flea population groups, but not the low- and medium-density groups. A weighted regression analysis gave prediction intervals for flea densities that provided satisfactory estimates of the actual numbers of fleas on the dogs.


Traumatic optic neuropathy accompanying orbital grease gun injury.
We report a case of traumatic optic neuropathy accompanying a grease gun injury to the orbit. A 48-year-old man with a grease gun injury visited our clinic with decreased visual acuity, proptosis and limited extraocular movement (EOM). Orbital CT revealed a crescent mass of fat in the medial intraconal space. The grease was exuded from a lacerated conjunctival wound. The visual evoked potential (VEP) test demonstrated a decreased response in the left eye. Proptosis and EOM were improved after surgical removal of the grease. Systemic high-dose corticosteroid therapy was administered for suspected traumatic optic neuropathy, after which VEP nearly recovered, while visual acuity was slightly improved. A second surgery for traumatic cataract did not further improve visual acuity.


Apelin-13 Pretreatment Promotes the Cardioprotective Effect of Mesenchymal Stem Cells against Myocardial Infarction by Improving Their Survival.
Although mesenchymal stem cell- (MSC-) based therapy has shown promising results for myocardial infarction (MI), low cell survival heavily limits its beneficial effects. Apelin plays an essential regulatory role in cell proliferation. This study was aimed at determining whether Apelin-13 pretreatment could improve the survival of MSCs in the ischemic heart and enhance their cardioprotective efficacy against MI. MSCs were pretreated with or without Apelin-13 for 24 hours and then exposed to serum deprivation and hypoxia (SD/H) for 48 hours. The mitochondrial morphology of MSCs was assessed by MitoTracker staining. The apoptosis of MSCs was determined by TUNEL staining. The level of mitochondrial reactive oxygen species (ROS) of MSCs was detected by Mito-Sox staining. MSCs and Apelin-13-pretreated MSCs were transplanted into the peri-infarct region in a mouse MI model. Apelin-13 pretreatment protected MSCs against SD/H-induced mitochondrial fragmentation and apoptosis. Apelin-13 pretreatment reduced ROS generation induced by SD/H in MSCs. Furthermore, Apelin-13 pretreatment enhanced the angiogenesis of MSCs under SD/H conditions. Mechanistically, Apelin-13 pretreatment inhibited SD/H-induced MSC apoptosis by downregulating mitochondrial fission via activation of the ERK pathway, and these effects were partially abrogated by ERK inhibitor U0126. Apelin-13 pretreatment promoted the survival of MSCs in the ischemic heart. Moreover, transplantation with Apelin-13-pretreated MSCs improved heart function and increased angiogenesis accompanied by decreased fibrosis compared with MSC transplantation at 28 days following MI. These findings reveal that pretreatment with Apelin-13 improves MSCs survival and enhances their therapeutic efficacy for MI. Our study provides a novel approach to improve MSC-based therapy for cardiovascular disease.


A Review of Cordocentesis: Percutaneous Umbilical Cord Blood Sampling.
We discuss the current indications, technical variation and procedure-related complications of percutaneous umbilical cord blood sampling (PUBS). The term PUBS is commonly used in the United States. Cordocentesis and funipuncture are equivalent terms. A needle guided by ultrasound is introduced into a blood vessel (usually the vein) of the umbilical cord to collect fetal specimen in PUBS. We conducted a literature search in PubMed indexed journals and analyzed all related articles on PUBS and cordocentesis. We chose this subject because it is a relatively new but convenient method that has both diagnostic and therapeutic value in fetal medicine. At present the only procedure that provides direct access to fetal circulation is PUBS. The most common clinical indication for PUBS is suspected fetal anemia. Other major indications for PUBS are the diagnosis of congenital infections, cytogenetic analysis, metabolic disorders, fetal growth restriction and hematologic disorders. Therapeutic applications of cordocentesis or puncture of the umbilical cord are in utero transfusions for rhesus alloimmunization and medication administration. PUBS also provides a direct assessment of fetal thyroid function diagnosing fetal thyroid disorders and helps administer therapy in utero. Literature demonstrates a low incidence of complications associated with percutaneous umbilical blood sampling. For PUBS, the true complication rate related to the method of sampling remains unclear. A few cases reported complications conducted PUBS for therapeutic purposes which naturally has a higher accident rate compared to diagnostic purposes. Although life-threatening complications are rare, there are potential risks that include bleeding from the puncture site, fetal bradycardia, vertical transmission of maternal infection. Therefore, PUBS should be performed at perinatal care centers by experienced physicians and the best time is between 17 to 40 weeks of gestation. There are three methods used to approach the umbilical cord that includes direct, indirect and free puncture. Anteriorly placed placenta allows an easier approach to the umbilical cord. The danger of abruption of placenta must be kept in mind while using this technique. The number of punctures should be limited to a maximum of 3 to reduce complications. According to a case series report, the mean time required for the procedure was 4 minutes with a fall in duration seen with increased experience. In conclusion, percutaneous blood sampling allows direct access to fetal circulation thus opening up new areas of prenatal diagnosis and therapy. PUBS is now a well-codified procedure. It is clear from our literature review that risks directly related to the technique are small. The indication of the procedure must be carefully chosen as the risk of complications of umbilical cord puncture is directly related to the severity of the condition. Complications such as bleeding and hematoma formation are related to duration and number of punctures which are operator-dependent. Thus, only highly trained personnel should conduct the procedure. The list of indications is extensive and growing. Nevertheless, this technique shows potential to open up new realms in the area of fetal medicine.


Assessing prevalence of antimicrobial use and infections using the minimal data set in Finnish long-term care facilities.
Of all residents (n = 12,784) for whom a minimum data set 2.0 form was completed in long-term care facilities (n = 253) using a Resident Assessment Instrument in April and September 2011 in Finland, 16% received antimicrobials, most commonly methenamine (42%) and trimethoprim (24%). The prevalence of urinary tract infections was 8%, wound infection 2%, and pneumonia 2%. Minimum data set form provides a feasible tool for collecting data on antibiotic use and infections in long-term care facilities.


Magnetic resonance imaging of the response of a mouse model of non-small cell lung cancer to tyrosine kinase inhibitor treatment.
Mutational activation of the gene for epidermal growth factor receptor (EGFR) is 1 of the main ways by which this receptor induces non-small cell lung cancers (NSCLC). Variant III EGFR (EGFRvIII) is a potential therapeutic target in NSCLC treatment because of the high frequency of deletion mutations in this protein. This study used noninvasive magnetic resonance imaging (MRI) to investigate the role of an EGFRvIII mutant in lung tumorigenesis and tumor maintenance as well as its response to the EGFR small molecule inhibitor erlotinib (Tarceva) on bitransgenic mice. Both spin-echo and gradient-echo sequences with and without cardiac and respiratory gating were performed to image the invasive mouse lung tumor driven by EGFRvIII mutation. Tumor volumes were measured based on 2-dimensional axial MRI; 3-dimensional rendering of the images were obtained to demonstrate the spatial location and distribution of the tumor in the lung. The MRI results indicated that the tumor driven by the EGFRvIII mutation was generated and maintained in the bitransgenic mice with the use of doxycycline. Tumor monitoring via MRI showed that Erlotinib can significantly inhibit the growth of tumor in vivo. MRI has the ability to image mouse lung tumor with different sequences focusing on tissue contrasts between tumor and surroundings. The MRI approaches in this work can be applied on other antitumor drug treatment evaluation in vivo when appropriate sequences are chosen.


Three validation studies of the personality assessment inventory short form.
We examined the psychometric properties of the Personality Assessment Inventory-Short Form (PAI-SF). Study 1 compared single-session short and full form PAI profiles of 200 outpatients, Study 2 examined PAI forms of 107 nonclinical adults across two administrations, and Study 3 compared correlations between full and short form scales and extratest variables. Study 1 correlations between short and full form scales ranged from 0.85 to 0.95 (Mdn = 0.91), with lower correlations, ranging from 0.59 to 0.86 for clinical scales (Mdn = 0.82), in Study 2. In Study 3 only 4 of 34 correlations differed significantly between extratest variables and the PAI versus the PAI-SF. These results indicate favorable psychometric properties of the PAI-SF.


Ethics is everybody's business, especially in regard to confidentiality.
... Every hospital needs a policy statement devoted to confidentiality. This task is a good assignment for a hospital ethics committee. In drafting such a statement, one area that should not be overlooked is respect for confidentiality in cases used for teaching, patient conferences, and interdisciplinary meetings, including the teaching of clinical ethics! The University of Virginia's (UVA) Hospital Ethics Committee is considering a new policy statement on confidentiality....


CT Scan in Subaxial Cervical Facet Injury: Is It Enough for Decision-Making?
Cross-sectional survey. Assessment of subaxial cervical facet injuries using the AO Spine Subaxial Cervical Spine Injury Classification System is based on CT scan findings. However, additional radiological evaluations are not directly considered. The aim of this study is to determine situations in which spine surgeons request additional radiological exams after a facet fracture. A survey was sent to AO Spine members from Latin America. The evaluation considered demographic variables, routine use of the Classification, as well as the timepoint at which surgeons requested a cervical MRI, a vascular study, and/ or dynamic radiographs before treatment of facet fractures. There was 229 participants, mean age 42.9 ± 10.2 years; 93.4% were men. Orthopedic surgeons 57.6% with 10.7 ± 8.7 years of experience in spine surgery. A total of 86% used the Classification in daily practice. An additional study (MRI/vascular study/and dynamic radiographs) was requested in 53.3%/9.6%/43.7% in F1 facet injuries; 76.0%/20.1%/50.2% in F2; 89.1%/65.1%/28.4% in F3; and 94.8%/66.4%/16.6% in F4. An additional study was frequently required: F1 72.5%, F2 86.9%, F3 94.7%, and F4 96.1%. Spine surgeons generally requested additional radiological evaluations in facet injuries, and MRI was the most common. Dynamic radiographs had a higher prevalence for F1/F2 fractures; vascular studies were more common for F3/F4 especially among surgeons with fewer years of experience. Private hospitals had a lower spine trauma cases/year and requested more MRI and more dynamic radiographs in F1/F2. Neurosurgeons had more vascular studies and dynamic radiographs than orthopedic surgeons in all facet fractures.


Structure and sum-frequency generation spectra of water on neutral hydroxylated silica surfaces.
Structural organization and vibrational sum-frequency generation (VSFG) spectra of water on crystalline and amorphous neutral silica surfaces were investigated by classical molecular dynamics simulations. The liquid phase represented with neat water and 1 M NaCl solution was analysed in terms of bonded interfacial layer (BIL), diffuse layer (DL) and bulk region. The simulations show that the structure of BIL depends on the surface morphology and density of surface OH groups. The water-silanol H-bond network and BIL structure are mainly insensitive to the presence of ions in the liquid phase. Molecules in DL of SiO2/neat water interfaces preferentially orient their OH bonds towards the surfaces. This effect is directly related to an effective negative charge of formally neutral surfaces. Ions of the electrolyte solution affect the intermolecular structure in DL by screening the surface electric field and by the chaotropic effect. Calculated phase-sensitive VSFG (Im[χ(2)]) spectrum of BIL features low-frequency negative and high-frequency positive bands. Characteristics of the positive band reflect the strength of water-surface interactions and surface crystallinity, while the position and shape of the negative band are common to all interfaces. The Im[χ(2)] spectrum of DL is dominated by a contribution from the third-order χ(3) susceptibility with the sign of the contribution directly related to the sign of electrostatic potential in the interfacial region. The DL spectrum is strongly affected by the presence of solvated ions. The computed intensity and Im[χ(2)] spectra of the amorphous silica/NaCl solution interface are in a good agreement with the conventional and phase-sensitive experimental VSFG spectra of fused SiO2/water system at low pH, in contrast to the spectra of the amorphous silica/neat water interface. Origins of the discrepancy are discussed.


Epilepsy in Sri Lanka: public awareness and attitudes.
Public awareness and attitudes toward epilepsy were surveyed in Sri Lanka using a self-administered questionnaire. The respondents belonged to seven different occupational categories--school children, teachers, university students, medical students, student nurses, army personnel and adult education participants. The results showed that the knowledge was deficient in many aspects among all the groups and the attitudes towards epilepsy and epileptics were marginally positive. The knowledge appeared to be most widespread with regards to symptomatology and least in the areas of aetiology and treatment. A significant proportion of the respondents seemed to harbour mythical beliefs about the disease. The study indicates the need for better utilization of the health and educational infrastructure of the country in educating the public and special groups.


Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells.
Interactions between lymphoma cells and stromal cells play a key role in promoting tumor survival and development of drug resistance. We identified differences in key signaling pathways between the JeKo-1 and REC-1 mantle cell lymphoma (MCL) cell lines, displaying different patterns of stromal cell adhesion and chemotaxis towards stroma-conditioned medium. The identified adhesion-regulated genes reciprocated important aspects of microenvironment-mediated gene modulation in MCL patients. Five-hundred and ninety genes were differently regulated between the cell lines upon adhesion to stromal cells, while 32 genes were similarly regulated in both cell lines. Regulation of B-cell Receptor (BCR) signature genes in adherent cells was specific for JeKo-1. Inhibition of BCR using siRNA or clinically approved inhibitors, Ibrutinib and Acalabrutinib, decreased adhesion of JeKo-1, but not REC-1 cells. Cell surface levels of chemokine receptor CXCR4 were higher in JeKo-1, facilitating migration and adhesion of JeKo-1 but not REC-1 cells. Surface levels of ICAM1 adhesion protein differ for REC-1 and JeKo-1. While ICAM1 played a positive role in adherence of both cell lines to stromal cells, S1PR1 had an inhibitory effect. Our results provide a model framework for further investigation of mechanistic differences in patient-response to new pathway-specific drugs.


Wound-healing effects of low-level laser therapy in diabetic rats involve the modulation of MMP-2 and MMP-9 and the redistribution of collagen types I and III.
The present study aimed to determine if LLLT restores the balance between mRNA expression of matrix metalloproteinases (MMP-2 and MMP-9) and also the balance between collagen types I and III during the healing process of diabetic wounds. One hundred and twenty male Wistar rats were distributed in Control (untreated non-diabetic rats: UND); Laser (laser treated in non-diabetic rats: LTND); Diabetic (diabetic rats non-laser treated rats: UD); and Diabetic+ Laser (diabetic rats laser treated: DLT) groups. The diabetes model using streptozotocin efficiently induced diabetes, as demonstrated through increased levels of blood glucose. Diode laser (50 mW, 660 nm, 4 J/cm(2), 80 s) was applied a single time after scare induction. Twenty-four hours after LLLT application, rats were euthanized, the scarred areas were collected for MMP-2 and MMP-9 mRNA analysis and also for histological analysis (inflammation and types I and III collagen). The results demonstrated that scare in untreated diabetic rats significantly increased the MMP-2 and MMP-9 expression compared with that in non-diabetic rats (p < 0.05), while LLLT significantly reduced MMP-2 and MMP-9 expression compared with that in untreated diabetic rats (p < 0.05). To conclude, the results also showed that LLLT was able to alter the expression of MMP-9 as well as accelerate the production of collagen and increase the total percentage of collagen type III in diabetic animals.


Thyroid hormone and leptin in the testis.
Leptin is primarily expressed in white adipose tissue; however, it is expressed in the hypothalamus and reproductive tissues as well. Leptin acts by activating the leptin receptors (Ob-Rs). Additionally, the regulation of several neuroendocrine and reproductive functions, including the inhibition of glucocorticoids and enhancement of thyroxine and sex hormone concentrations in human beings and mice are leptin functions. It has been suggested that thyroid hormones (TH) could directly regulate leptin expression. Additionally, hypothyroidism compromises the intracellular integration of leptin signaling specifically in the arcuate nucleus. Two TH receptor isoforms are expressed in the testis, TRa and TRb, with TRa being the predominant one that is present in all stages of development. The effects of TH involve the proliferation and differentiation of Sertoli and Leydig cells during development, spermatogenesis, and steroidogenesis. In this context, TH disorders are associated with sexual dysfunction. An endocrine and/or direct paracrine effect of leptin on the gonads inhibits testosterone production in Leydig cells. Further studies are necessary to clarify the effects of both hormones in the testis during hypothyroidism. The goal of this review is to highlight the current knowledge regarding leptin and TH in the testis.


Mechanism of action of polymeric aurintricarboxylic acid, a potent inhibitor of protein--nucleic acid interactions.
The mechanism of inhibition of protein--nucleic acid complex formation by polymeric aurintricarboxylic acid (ATA) was investigated by proton magnetic resonance spectroscopy. The approach was the synthesis of totally deuterated ATA, followed by a 100-MHz proton magnetic resonance study of its interaction with bovine pancreatic ribonuclease A (RNase), a model nucleic acid binding protein. The binding of ATA to RNase elicited chemical shift changes and line broadening in the C(2)--H resonances of histidyl residues 12 and 119, both of which are located in the active site, whereas that of histidyl residue 105, which resides on the exterior of the protein structure, is unaffected. (Histidyl residue 48 is not observed under our conditions except at high pH.) The epsilon-methylene protons of the lysyl side chains were also broadened upon the binding of ATA. Polymeric ATA displaces cytidine 2'-monophosphate and cytidine 3'-monophosphate from the active site of the enzyme as revealed by nuclear magnetic resonance spectroscopy. These observations suggest that the mechanism of action of ATA involves competition between the nucleic acid and the polymeric ATA for binding in the active site of the protein. Electron spin resonance spectroscopy reveals that polymeric ATA is a stable free radical, thus accounting for the major line broadening effect upon binding to protein. This finding may provide a powerful means of probing the nucleic acid binding site of proteins by proton magnetic resonance spectroscopy.


A Single-Port Robotic Platform for Laparoscopic Surgery with a Large Central Channel for Additional Instrument.
A new approach to a surgical robotic platform for single incision laparoscopic or natural orifice transluminal endoscopic surgery is presented in this paper This platform allows insertion of up to four instruments including the robotic arms and the camera through a single cannula at the same footprint. After insertion of all instruments, a large central channel of 15 mm diameter is kept clear for the passage of additional laparoscopic instruments, such as passage or retrieval of suture needles, and/or suction irrigators which greatly facilitates the performance of complex surgical procedures. Phantom and animal trials have been performed to evaluate the insertion and retrieval sequences. These important features were made possible by internally-motorized robotic arms with 7 degrees of freedom and with no external mechanical device connections. The whole platform, together with the 3 degrees of freedom from the swivel system that support the cannula, has altogether 10 degrees of freedom to allow the operation of complex surgeries and access to all quadrants of the abdominal cavity. This new single-port robotic platform paves a new development direction for future non-invasive surgery.


[Study of Functional Magnetic Resonance Imaging at Resting State for Patients in Sub-health Status].
This study sought to reveal the difference of brain functions at resting-state between subjects with sub-health and normal controls by using the functional magnetic resonance imaging (fMRI) technology. Resting-state fMRI scans were performed on 24 subjects of sub-health and on 24 healthy controls with gender, age and education matched with the sub-health persons. Compared to the healthy controls, the sub-health group showed significantly higher regional homogeneity (ReHo) in the left post-central gyrus and the right post-central gyrus. On the other hand, the sub-health group showed significantly lower ReHo in the left superior frontal gyrus, in the right anterior cingulated cortex and ventra anterior cingulate gyrus, in the left dorsolateral frontal gyrus, and in the right middle temporal gyrus. The Significant difference in ReHo suggests that the sub-health persons have abnormalities in certain brain regions. It is proved that its specific action and meaning deserves further assessment.


The effects of captopril on rat aortic angiotensin-converting enzyme.
Angiotensin -converting enzyme (ACE) activity was found to be present within the rat aorta using radioenzymatic techniques. Forty-two percent of the enzyme activity was localized within the tunica media. Using an equilibrium dialysis cell system that insured equal free captopril concentrations in both plasma and aorta, converting enzyme in both tissues was observed to possess similar dissociation constants for the inhibitor. Four daily intraperitoneal doses, but not a single dose, of captopril led to a persistent inhibition of aortic-converting enzyme 24 h after final drug administration. Plasma-converting enzyme activity was changed at this time. These results suggest that different pools of converting enzyme recover form captopril inhibition at different rates. The prolonged inhibition of aortic ACE is discussed in terms of drug accumulation within the vessel wall, and the effect of such accumulation on the persistent antihypertensive actions of captopril are also discussed.


Critical role for Stat3 in T-dependent terminal differentiation of IgG B cells.
Stat proteins are latent cytoplasmic transcription factors that are crucial in many aspects of mammalian development. In the immune system, Stat3 has distinct roles in T-cell, neutrophil, and macrophage function, but a role for Stat3 in B-cell development, particularly in the terminal differentiation of B cells into antibody-secreting plasma cells, has never been directly tested. In this study, we used the Cre/lox system to generate a mouse strain in which Stat3 was conditionally deleted in the B-cell lineage (Stat3(fl/fl)CD19(Cre/+)). B-cell development, establishment of the peripheral B-cell compartment, and baseline serum antibody levels were unperturbed in Stat3(fl/fl)CD19(Cre/+) mice. Strikingly, Stat3(fl/fl)CD19(Cre/+) mice displayed profound defects in T-dependent (TD) IgG responses, but normal TD IgM, IgE, and IgA responses and T-independent (TI) IgM and IgG3 responses. In addition, germinal center (GC) formation, isotype switching, and generation of memory B cells, including IgG+ memory cells, were all intact in Stat3(fl/fl)CD19(Cre/+) mice, indicating that the requirement for Stat3 was limited to plasma cell differentiation. These results demonstrate a profound yet highly selective role for Stat3 in TD IgG plasma cell differentiation, and therefore represent a unique example of a transcription factor regulating isotype-specific terminal B-cell differentiation.


A role for Yip1p in COPII vesicle biogenesis.
Yeast Ypt1p-interacting protein (Yip1p) belongs to a conserved family of transmembrane proteins that interact with Rab GTPases. We encountered Yip1p as a constituent of ER-derived transport vesicles, leading us to hypothesize a direct role for this protein in transport through the early secretory pathway. Using a cell-free assay that recapitulates protein transport from the ER to the Golgi complex, we find that affinity-purified antibodies directed against the hydrophilic amino terminus of Yip1p potently inhibit transport. Surprisingly, inhibition is specific to the COPII-dependent budding stage. In support of this in vitro observation, strains bearing the temperature-sensitive yip1-4 allele accumulate ER membranes at a nonpermissive temperature, with no apparent accumulation of vesicle intermediates. Genetic interaction analyses of the yip1-4 mutation corroborate a function in ER budding. Finally, ordering experiments show that preincubation of ER membranes with COPII proteins decreases sensitivity to anti-Yip1p antibodies, indicating an early requirement for Yip1p in vesicle formation. We propose that Yip1p has a previously unappreciated role in COPII vesicle biogenesis.


Forearm haemodynamics and blood pressure variability in hypertensive patients.
Ambulatory blood pressure variability and forearm haemodynamics were measured in 23 untreated hypertensive patients with a mean casual blood pressure of 162/102(11/9) mmHg (without target organ damage). There was a good inverse correlation between blood pressure variability and the ability of the forearm resistance vessels to dilate after a period of venous occlusion. Previous work has shown that this vasodilatory component of the response to forearm venous occlusion is significantly reduced in hypertensive patients compared with normotensive controls and is probably an indicator of the compliance properties of these vessels. The present results suggest that blood pressure variability is greater when resistance vessels are stiffer and emphasise the need to account for this vascular factor in studies of blood pressure behaviour.


The effects of smoking and silica exposure on pulmonary epithelial permeability: a radioaerosol study with 99mTc-DTPA.
1. Pulmonary epithelial permeability (PEP) as evaluated by the clearance rate (K, %/min) of 99mTc-DTPA from lung to blood was measured in 4 groups of individuals: 10 normal controls; 10 smokers; 15 silica dust-exposed ceramic workers, 7 without chest X-ray alternations; and 8 with mild radiographic alterations, consistent with silicosis (small opacities of up to 1.5 mm diameter). 2. All subjects had normal pulmonary function tests. The mean clearance rates of smokers (3.0 %/min) and silica-exposed workers with X-ray changes (2.9 %/min) were accelerated compared to controls (1.2%/min) (P less than 0.05). Ceramic workers with normal X-rays had mean clearance rates (2.0 %/min) similar to controls. However, 3 of 7 (43%) had K values higher than the upper limit of the 95% confidence interval for the control mean. 3. Comparison of regional K (%/min) values with controls indicated faster clearance of 99mTc-DTPA in the upper lung regions of smokers. There was also increased clearance in the silicotic workers although of more uniform distribution over the lung regions analyzed. 4. Both smokers and ceramic workers exposed to a silica dust environment, with or without chest X-ray alterations, may show increased PEP compared to controls. As measurement of this parameter appears to be a sensitive index of lung injury, follow-up studies involving workers exposed to noxious dust are proposed to relate alterations in PEP to early silicosis and to the extent of lung injury.


A rare case of interstitial pneumonitis after tandem high-dose melphalan conditioning and autologous stem cell transplantation in multiple myeloma.
A 57-yr-old woman with multiple myeloma received an autologous tandem transplant at a 4-month interval. She was conditioned twice with 225 mg/m2 melphalan. After the second transplant, interstitial pneumonitis (IP) ensued. The clinical course was life threatening and mechanical ventilation was required for 32 d. All attempts to identify an infectious agent failed. A presumptive diagnosis of idiopathic IP, possibly related to melphalan toxicity, was made. High-dose methylprednisolone administration led to rapid and durable improvement. Melphalan was employed for conditioning in the tandem setting with an interval of only 3-4 months between two courses or a dose elevation to 225 instead of 200 mg/m2, may have induced IP which responded favorably to methylprednisolone.


Expression of metalloproteinase-9 in patients with mild and severe forms of gastroesophageal reflux disease.
Gastroesophageal reflux disease develops when the stomach contents causes troublesome symptoms and complications. Mild forms are non-erosive and erosive esophagitis, and severe forms are Barrett's esophagus and Esophageal adenocarcinoma. Matrix metalloproteinases are endopeptidases that can degrade components of the extracellular matrix, they play an important role in tumor invasion as well as in metastasis. To correlate the expression of metalloproteinase 9 (MMP-9) in esophageal biopsies from patients with mild and severe forms of Gastroesophageal reflux disease. Cross-sectional study. The expression of MMP-9 was determined in biopsies of esophageal tissue of patients with mild and severe GRD. The included variables were age, sex, diagnosis, smoking and alcoholic habits, body mass index (BMI) and expression of MMP-9. Descriptive statistics was performed, Kappa for concordance in diagnosis as well as X2. There were 50 patients, 32 (64%) men and 18 (36%) women, mean age 52.13 ± 14.75 years of age. 12 (24%) with smoking and 7 (14%) with alcoholism. Average BMI was 26.71 ± 4.07 kg/m2 (15 to 33); 40 (80%) with obesity. The inter observer concordance for histopathological diagnosis was 1.0 and 0.84 for esophagitis degrees. 27 (54%) patients had esophagitis, 16 (32%) Barrett's esophagus and 7 (14%) esophageal cancer. There was expression of MMP-9 in four patients with esophagitis, five with Barrett's esophagus and five with esophageal cancer. Statistical significance was found between the expression of MMP-9 and smoking (p = 0.011) and histopathological diagnosis (p = 0.052). The expression of MMP-9 is most common in severe forms compared to the mild forms of GRD.


The diagnosis of depression and the DSMs.
The classification of depression in DSM-III and DSM-III-R is radically changed from that of DSM-I and DSM-II. To understand the many changes, this paper explores early diagnostic systems, newer research studies, DSM-I, DSM-II, DSM-III, and DSM-III-R. A conclusion is reached that DSM-III and DSM-III-R offer both advantages and disadvantages to DSM-I and DSM-II. These are detailed in the paper.


Endothelial apoptosis initiates acute blood-brain barrier disruption after ionizing radiation.
Acute disruption of blood-brain barrier (BBB) is well recognized after radiation therapy to the central nervous system (CNS). We assessed the genetic regulation of acute BBB disruption and its relationship to vascular endothelial cell death in the CNS after irradiation. Adult rats were given graded single doses of X-ray to the cervical spinal cord. At different time intervals after irradiation, the irradiated spinal cord was processed for histological and immunohistochemical analysis. Disruption of blood-spinal cord barrier was assessed using albumin immunohistochemistry, i.v. injection of Evans blue dye, and (99m)Tc-diethylenetriamine pentaacetic acid. In the rat spinal cord, there was a dose-dependent apoptotic response during the first 24 h after irradiation, and apoptotic cells consisted of both endothelial and glial cells, as described previously (1, 2). A dose-dependent reduction in endothelial cell density was observed at 24 h after irradiation. This was associated with a similar dose-dependent disruption in blood-spinal cord barrier as demonstrated by albumin immunohistochemistry. Radiation-induced apoptosis in endothelial cells has been shown to be dependent on the acid sphingomyelinase (ASMase) pathway. After a single 50-Gy dose to the cervical spinal cord of ASMase +/+ mice, there was a 47.7% reduction in endothelial cell density at 24 h compared with nonirradiated controls. No decrease in endothelial cell density was observed in irradiated ASMase -/- mice. In the irradiated spinal cord of ASMase +/+ mice, there was evidence of albumin immunoreactivity and Evans blue dye staining around microvessels, and (99m)Tc-diethylenetriamine pentaacetic acid uptake increased at 24 h. Nonirradiated controls and the irradiated spinal cord of ASMase -/- mice demonstrated no evidence of leakage. We conclude that apoptosis of endothelial cells initiates acute BBB disruption in the CNS after irradiation and that acute BBB disruption after irradiation is mediated by the ASMase pathway.


Immunological function of the blood-cerebrospinal fluid barrier.
Because the brain lacks a true lymphatic system, it is unclear how peripheral lymphocytes recognize foreign antigens present in the central nervous system. This report demonstrates that the choroid plexus, which constitutes the blood-cerebrospinal fluid barrier, is able to present foreign antigen to, and stimulate the proliferation of, peripheral helper T lymphocytes through an Ia-dependent, major histocompatibility complex-restricted mechanism. Furthermore, in vivo, choroid plexus epithelial cells have access to, and are capable of taking up, virus-sized particles injected elsewhere into the cerebrospinal fluid. Thus these data suggest that the blood-cerebrospinal fluid barrier may play a role in immunological communication between the central nervous system and periphery, a function relevant to the initiation of immunological responses to central nervous system infections and autoimmune processes and for the surveillance of tumor cells in the cerebrospinal fluid.


Biodecolourisation of reactive red an industrial dye by Phlebia spp. .
Four white rot fungi namely Phanerochaete chrysosporium, Phlebia floridensis, P. radiata and P. brevispora were selected for their ligninolytic enzymes viz., lignin peroxidase, manganese peroxidase and laccase. Cell free enzyme extracts (as such and concentrated) obtained from these fungi were tested for their ability to decolourise reactive red 28 (Congo red), an industrial dye. The use of cell free enzyme extracts helped to overcome the problem of adsorption of dye to mycelia. Laccase production was best expressed in P. brevispora. Increase in decolourisation percentage by concentrated culture extract was comparable to increase in enzyme activity. P. floridensis proved to be a better dye decolouriser in comparison to Pha. chrysosporium, thus showing its potential for biocleaning of industrial wastes and wastewaters.


Clinical Applications of In Vivo Confocal Microscopy in Keratorefractive Surgery.
To review the contribution of in vivo confocal microscopy (IVCM) to the understanding of corneal wound healing following refractive surgery, and its role in the diagnosis and management of complications arising from keratorefractive procedures. Review of the basic science and clinical literature relating to the study of keratorefractive surgical procedures using IVCM. Extensive research using IVCM has generated a comprehensive understanding of tissue responses after corneal refractive surgery. Epithelial thickness and stromal keratocyte density can be quantified postoperatively and studied longitudinally. Corneal nerve loss and subsequent reinnervation has been characterized and differs significantly between laser refractive techniques. IVCM has also been used to study complications arising from postoperative inflammation (diffuse lamellar keratitis, central toxic keratopathy, ring keratitis, and ectasia), infection (microbial keratitis), and neuropathy (dry eye and neuralgia). This imaging technique can have a critical role in the diagnosis of these complications and subsequent monitoring of treatment response. Manual processing of IVCM images is time-consuming and there may be significant interobserver and intraobserver variability with poor repeatability. However, increasing automation and the use of artificial intelligence is improving the speed and accuracy of image analysis. IVCM has historically been confined to a research setting because image capture and subsequent processing was extremely labor intensive. However, advances in both hardware and software capabilities promise to allow the use of IVCM in routine clinical practice. Real-time evaluation of the cornea at a cellular level will be particularly useful in patients with inflammatory, infectious, or neuropathic complications of keratorefractive surgery. [J Refract Surg. 2021;37(7):493-503.].


[Advances in basic and clinical research on hepatocellular carcinoma in 2016].
Hepatocellular carcinoma (HCC) is still one of common malignant cancers worldwide, with increasing incidence and mortality rates. Early diagnosis and effective treatment for HCC remain to be explored. This article introduces the research advances in the early specific diagnosis and effective therapies for HCC in 2016, such as molecular markers in the specific diagnosis and targeted therapy for HCC, main therapeutic regimens, robot-assisted liver resection, and no-touch radiofrequency ablation.


[Immunohistochemical studies of hemangioblastoma with glial fibrillary acidic protein].
Sixteen cases of CNS hemangioblastoma were examined for glial fibrillary acidic protein (GFAP) using the immunoperoxidase method. In 13 cases GFAP-positive cells were found in the tumor. In all positive cases reactive gliosis in the form of trapped reactive astrocytes and their cytoplasmic processes penetrated the margin of the tumor. In 4 of the positive cases GFAP-positive cells were present deep in the tumor. Aggregates of GFAP-positive cells and fibrils were especially prominent in a recurrent case. Because hemangioblastomas grow without capsule into the cerebellar tissue, it is considered that reactive astrocytes and their fibrils are easily included and trapped within the tumor. In two cases GFAP-positive plump stromal cells, which were definitely different from the reactive astrocytes, were seen. They were neighbored with the dense gliotic foci or on and around the microcyst wall. This may be interpreted as that the stromal cells have a capacity to incorporate the extracellular GFAP derived from the intratumoral gliotic foci or cysts.


Torsional Profiles of Thiophene and Furan Oligomers: Probing the Effects of Heterogeneity and Chain Length.
A systematic analysis of the torsional profiles of 55 unique oligomers composed of two to four thiophene and/or furan rings (n = 2 to 4) has been conducted using three density functional theory (DFT) methods along with MP2 and three different coupled-cluster methods. Two planar or quasi-planar minima were identified for each n = 2 oligomer system. In every case, the torsional angle (τ) between the heteroatoms about the carbon-carbon bond connecting the two rings is at or near 180° for the global minimum and 0° for the local minimum, referred to as anti and syn conformations, respectively. These oligomers have rotational barrier heights ranging from ca. 2 kcal mol-1 for 2,2'-bithiophene to 4 kcal mol-1 for 2,2'-bifuran, based on electronic energies computed near the CCSD(T) complete basis set (CBS) limit. The corresponding rotational barrier for the heterogeneous 2-(2-thienyl)furan counterpart falls approximately halfway between those values. The energy differences between the minima are approximately 2 and 0.4 kcal mol-1 for the homogeneous 2,2'-bifuran and 2,2'-bithiophene, respectively, whereas the energy difference between the planar local and global minima (at τ = 0 and 180°, respectively) is only 0.3 kcal mol-1 for 2-(2-thienyl)furan. Extending these three oligomers by adding one or two additional thiophene and/or furan rings resulted in only minor changes to the torsional profiles when rotating around the same carbon-carbon bond as the two-ring profiles. Relative energy differences between the syn and anti conformations were changed by no more than 0.4 kcal mol-1 for the corresponding n = 3 and 4 oligomers, while the rotational barrier height increased by no more than 0.8 kcal mol-1.


Septal extension graft in "closed" revision rhinoplasty: A simplified technique.
The septal extension graft (SEG) is widely used in secondary rhinoplasty for correction of a short nose with loss of tip support and projection, columellar retraction, and hyper-rotated tip secondary to an overresection of the caudal septum. Although SEG precise fixation can be relatively easy in the external approach, the difficulties of SEG placement in "closed" rhinoplasty can be discouraging. To describe an easy surgical technique for SEG placement in endonasal revision rhinoplasty and to analyze the aesthetic results of the procedure. Thirty-eight patients were submitted to an endonasal approach revision rhinoplasty with endonasal placement of SEG for the correction of a short nose with a hypoprojected and hyper-rotated nasal tip. Pre- and postoperative nasal length, tip projection, and tip rotation (nasolabial and lobulocolumellar angles) were measured for each patient. An increase (mean ± standard deviation) of nasal length by 15.02 ± 3.91% and an augmentation of tip projection by 11.34 ± 2.26% were noticed after surgery with respect to preoperative conditions. A significant (p < 0.001) decrease in the columellar-labial angle was recorded on postoperative (91.23 ± 3.85°) examination with respect to preoperative (99.81 ± 6.49°) conditions. A decrease (p < 0.001) in the columellar-lobular angle was noted on postoperative assessment (34.02 ± 5.28°) with respect to preoperative examination (50.02 ± 0.36°). No relevant postoperative complication was recorded. The "endonasal" approach described for SEG placement was an easy and reliable procedure to treat a short nose with loss of tip support and projection, columellar retraction, and hyper-rotated tip, especially in revision surgery. The advantages of our technique over previously described approaches were reported.


Fluorescence detector for capillary separations fabricated by 3D printing.
A simple inexpensive light-emitting diode (LED)-based fluorescence detector for detection in capillary separations is described. The modular design includes a separate high power LED source, detector head, designed in the epifluorescence arrangement, and capillary detection cells. The detector head and detection cells were printed using a 3D printer and assembled with commercially available optical components. Optical fibers were used for connecting the detector head to the LED excitation source and the photodetector module. Microscope objective or high numerical aperture optical fiber were used for collection of the fluorescence emission from the fused silica separation capillary. As an example, mixture of oligosaccharides labeled by 8-aminopyrene-1,3,6-trisulfonate (APTS) was separated by capillary zone electrophoresis and detected by the described detector. The performance of the detector was compared with both a semiconductor photodiode and photomultiplier as light sensing elements. The main advantages of the 3D printed parts, compared to the more expensive alternatives from the optic component suppliers, include not only cost reduction, but also easy customization of the spatial arrangement, modularity, miniaturization, and sharing of information between laboratories for easy replication or further modifications of the detector. All information and files necessary for printing the presented detector are enclosed in the Supporting Information.


Abdominal wall recurrence after laparoscopic colectomy for colon cancer.
Although rare, abdominal wall recurrences after laparoscopic surgery for cancer have been increasing at an alarming rate as the range and sheer number of laparoscopic surgical procedures have increased. Overall, 13 case reports of abdominal wall cancer recurrence after laparoscopic surgery have been published. We present the fourth known case of abdominal wall recurrence after laparoscopic colectomy involving a patient with a TNM stage III (T3, N2, M0) colon cancer. Recurrent cancer was located in the abdominal wall incision and also in all four port sites 9 months after surgery. These four cases have all involved patients with advanced cancers of the right side of the colon who underwent a laparoscopic-assisted right hemicolectomy. These cases of abdominal wall cancer recurrence carry ominous implications for the future of laparoscopic surgical procedures involving colorectal malignancy. Recurrent cancer in minilaparotomy incisions may simply be due to local spread of cancerous cells. However, remote port site recurrence may be due to the liberation of cancer cells throughout the abdomen from advanced colorectal cancer no longer confined to the bowel wall facilitated by intraperitoneal carbon dioxide insufflation during laparoscopy. Abdominal wall cancer recurrence is enhanced by the laparoscopic approach to colectomy for colorectal cancer. Except for controlled, clinical studies, laparoscopic colectomy for malignancy should be abandoned.


Temporal stability of the transcendent actualization inventory.
This paper describes a study of the temporal stability of a new inventory, the Transcendent Actualization Inventory, which aims to estimate actualization of psychospiritual potential. For 200 subjects, the test-retest reliability was .84 for Time 1 vs Time 2. Cronbach coefficient alpha was .81 at Times 1 and 2, as previously reported (N=478).


Severe bleeding from submucosal lipoma of the duodenum.
Two patients with a duodenal lipoma had severe gastrointestinal bleeding. Duodenal lipoma is relatively rare and an even rarer source of severe gastrointestinal bleeding. Endoscopy and routine radiological examination of the gastrointestinal tract may suggest the diagnosis, but computed tomography allows a definitive preoperative diagnosis. Surgery is indicated in order to avoid complications.


Temporal lobe arachnoid cyst-attention deficit disorder syndrome: role of the electroencephalogram in diagnosis.
I report three childhood cases of temporal lobe arachnoid cyst in association with attention deficit hyperactivity disorder (ADHD). The cysts were identical in location, situated in the left middle cranial fossa, and involved the medial aspect of the temporal lobe. The diagnosis by MRI was determined following EEGs obtained because of headaches, episodes suggestive of partial seizures or tremors, and abnormal neurologic signs. The etiology of the cysts appeared to be developmental and not related to trauma or hemorrhage. EEGs showed focal epileptiform or slow wave abnormalities involving the left temporal region and correlating with the location of the structural temporal fossa lesions. Surgery was not advised, and headaches resolved after dietary modification or when methylphenidate medication for ADHD was discontinued. The relation of the arachnoid cyst to the headaches is not definitely determined, but a causal association with the ADHD is considered plausible because of coincidental learning and language disabilities that might be explained by temporal lobe and sylvian region pathology. This appears to be the first report of the association of ADHD and temporal fossa arachnoid cyst in children. The EEG is a valuable diagnostic test in patients with ADHD complicated by headaches, seizures, or focal neurologic signs. Future cases of arachnoid cyst involving the temporal lobe and diagnosed because of headache or seizures should be investigated psychologically for associated attention deficits and learning disabilities.


BIRD PREDATION AS A SELECTIVE AGENT IN A BUTTERFLY POPULATION.
In a population of the checkerspot butterfly, Euphydryas chalcedona, the detached wings of 309 individuals that had been attacked and eaten by birds were collected during a single flight season. During this time period a representative sample of 296 live butterflies in this population was photographed. Comparison of sex ratio and coloration of those butterflies that had been attacked with those that had not showed, first, that birds attacked slightly more females than males; and second, that among males, which are extremely variable in the amount of red on the forewing, birds attacked the less red individuals.


Providing nursing care for erectile dysfunction.
Erectile dysfunction may affect one in 10 men as they age. The publicity surrounding the introduction of Viagra has led to more men coming forward for treatment for ED. Specialist urology nurses have the communication and counselling skills necessary to provide quality care to this patient group.


Organocatalytic Para-Selective Amination of Phenols with Iminoquinone Monoacetals.
A highly selective para C-H amination of unprotected phenols with iminoquinone acetals was realized, giving the functional phenols in good to excellent yields. Overall, this transformation is operationally simple, proceeds with readily available phenols, and has wide substrate scope and low catalyst loading. The biarylamine product is stochastically formed via [5,5]-sigmatropic rearrangement of a mixed acetal species which is generated in situ under the reaction conditions.


Left Inferior Pulmonary Vein-related Reentry Identified Using High-density Activation and Voltage Mapping in Combination with Entrainment Mapping.
A 61-year-old man with highly symptomatic palpitations presented 13 months after undergoing pulmonary vein isolation for paroxysmal atrial fibrillation. A 12-lead electrocardiogram revealed atrial tachycardia, and the patient was scheduled for mapping, which revealed two regions of reconnection along the posterior part of the region of the left inferior pulmonary vein.


Improving Detection of Multiple Sclerosis Lesions in the Posterior Fossa Using an Optimized 3D-FLAIR Sequence at 3T.
There is no consensus regarding the best MR imaging sequence for detecting MS lesions. The aim of our study was to assess the diagnostic value of optimized 3D-FLAIR in the detection of infratentorial MS lesions compared with an axial T2-weighted imaging, a 3D-FLAIR with factory settings, and a 3D double inversion recovery sequence. In this prospective study, 27 patients with confirmed MS were included. Two radiologists blinded to clinical data independently read the following sequences: axial T2WI, 3D double inversion recovery, standard 3D-FLAIR with factory settings, and optimized 3D-FLAIR. The main judgment criterion was the overall number of high-signal-intensity lesions in the posterior fossa; secondary objectives were the assessment of the reading confidence and the measurement of the contrast. A nonparametric Wilcoxon test was used to compare the MR images. Twenty-two patients had at least 1 lesion in the posterior fossa. The optimized FLAIR sequence detected significantly more posterior fossa lesions than any other sequence: 7.5 versus 5.8, 4.8, and 4.1 (P values of .04, .03, and .03) with the T2WI, the double inversion recovery, and the standard FLAIR, respectively. The reading confidence index was significantly higher with the optimized FLAIR, and the contrast was significantly higher with the optimized FLAIR than with the standard FLAIR and the double inversion recovery. An optimized 3D-FLAIR sequence improved posterior fossa lesion detection in patients with MS.


Osteonecrosis of the jaw associated with everolimus: A case report.
Everolimus, a mammalian target of rapamycin inhibitor, has recently been approved for the treatment of metastatic estrogen receptor-positive breast cancer, at a daily dose of 10 mg in combination with exemestane. Osteonecrosis of the jaw (ONJ) is a rare but severe condition, characterized by exposed necrotic bone, and is associated with various drugs that are often used to treat advanced malignancies. We herein report the case of a patient with breast cancer who developed ONJ during treatment with everolimus, which improved after discontinuation of the drug. To the best of our knowledge, this is the first reported case of everolimus-associated ONJ in a patient receiving everolimus for metastatic breast cancer. In 2014, an 80-year-old woman was started on treatment with everolimus and exemestane for stage IIB estrogen receptor-positive breast cancer. Within 2 months, the left side of her face became edematous, with localized heat and tenderness of the left mandibular region and a 3-mm round area of exposed bone. There was purulent discharge and the surrounding gingiva was edematous and erythematous. The left mandible exhibited a low signal intensity area on T1-weighted magnetic resonance imaging. Treatment was discontinued and ONJ showed improvement after 2 months. Therefore, when prescribing everolimus for metastatic breast cancer, oncologists should be aware of the possibility of ONJ as a complication.


Seasonal impact of blending oxygenated organics with gasoline on motor vehicle tailpipe and evaporative emissions.
Emissions from a 1988 GM Corsica with adaptive learning closed loop control were measured with 4 fuels at 40, 75, and 90 degrees F. Evaporative and exhaust emissions were examined from each fuel at each test temperature. Test fuels were unleaded summer grade gasoline; a blend of this gasoline containing 8.1 percent ethanol; a refiner's blend stock; and the blend stock containing 16.2 percent methyl tertiary butyl ether. The ethanol and MTBE blends contained 3.0 percent oxygen by weight. Regulated emissions (total hydrocarbons, carbon monoxide, and oxides of nitrogen), detailed aldehydes, detailed hydrocarbons, ethanol, MTBE, benzene, and 1,3-butadiene were determined. The highest levels of regulated emissions were produced at the lower temperature. Blended fuels produced almost twice the evaporative hydrocarbon emissions at high temperatures as did the base fuels. Benzene emissions varied with fuels and operating temperatures, while 1,3-butadiene emissions decreased slightly with increasing temperatures. Formaldehyde emissions were not sensitive to fuel or temperature changes. Ethanol fuel blend total aldehyde emissions increased by 40 percent due to increased acetaldehyde emissions. Fuel blends had approximately a 3 percent economy decrease. The MTBE fuel blend appeared to offer the most reduction in total hydrocarbon, carbon monoxide, and oxides of nitrogen for the fuels and temperatures tested.


Pulsed laser assisted high-throughput intracellular delivery in hanging drop based three dimensional cancer spheroids.
Targeted intracellular delivery of biomolecules and therapeutic cargo enables the controlled manipulation of cellular processes. Laser-based optoporation has emerged as a versatile, non-invasive technique that employs light-based transient physical disruption of the cell membrane and achieves high transfection efficiency with low cell damage. Testing of the delivery efficiency of optoporation-based techniques has been conducted on single cells in monolayers, but its applicability in three-dimensional (3D) cell clusters/spheroids has not been explored. Cancer cells grown as 3D tumor spheroids are widely used in anti-cancer drug screening and can be potentially employed for testing delivery efficiency. Towards this goal, we demonstrated the optoporation-based high-throughput intracellular delivery of a model fluorescent cargo (propidium iodide, PI) within 3D SiHa human cervical cancer spheroids. To enable this technique, nano-spiked core-shell gold-coated polystyrene nanoparticles (ns-AuNPs) with a high surface-to-volume ratio were fabricated. ns-AuNPs exhibited high electric field enhancement and highly localized heating at an excitation wavelength of 680 nm. ns-AuNPs were co-incubated with cancer cells within hanging droplets to enable the rapid aggregation and assembly of spheroids. Nanosecond pulsed-laser excitation at the optimized values of laser fluence (45 mJ cm-2), pulse frequency (10 Hz), laser exposure time (30 s), and ns-AuNP concentration (5 × 1010 particles per ml) resulted in the successful delivery of PI dye into cancer cells. This technique ensured high delivery efficiency (89.6 ± 2.8%) while maintaining high cellular viability (97.4 ± 0.4%), thereby validating the applicability of this technique for intracellular delivery. The optoporation-based strategy can enable high-throughput single cell manipulation, is scalable towards larger 3D tissue constructs, and may provide translational benefits for the delivery of anti-cancer therapeutics to tumors.


A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.
Pompe disease is a recessively inherited and often fatal disorder caused by the deficiency of acid α-glucosidase, an enzyme encoded by the GAA gene and needed to break down glycogen in lysosomes. This glycogen storage disease type II has been reported also in Swedish Lapphund dogs. Here we describe the genetic defect in canine Pompe disease and show that three related breeds from Scandinavia carry the same mutation. The affected dogs are homozygous for the GAA c.2237G>A mutation leading to a premature stop codon at amino acid position 746. The corresponding mutation has previously been reported in humans and causes infantile Pompe disease in combination with a second fully deleterious mutation. The affected dogs from both the Finnish as well as the Swedish breed mimic infantile-onset Pompe disease genetically, but also clinico-pathologically. Therefore this canine model provides a valuable tool for preclinical studies aimed at the development of gene therapy in Pompe disease.


Chimeric antigen receptor-modified T-cell therapy for bone marrow and skin relapse Philadelphia chromosome-like acute lymphoblastic leukemia: A case report.
Chimeric antigen receptor-modified T-cell (CART) therapy has revolutionized the treatment of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). However, the capacity of CART therapy has not yet been fully elucidated. An 18-year-old Chinese male patient presented with multiple firm masses on the skin all over his body following regular chemotherapy. Bone marrow smear and skin biopsy confirmed that it was a bone marrow and skin relapse from the initial B-cell ALL. CD19 CART-cell therapy was performed to manage the bone marrow and skin of the relapsed B-cell ALL. During CART-cell therapy, cytokine release syndrome and central nervous encephalopathy occurred. Eventually, the lesions disappeared, and the bone marrow and skin tested minimal residual disease (MRD) negative. The patient achieved complete remission (CR). Fourteen days after testing MRD negative, he received allogeneic hematopoietic stem-cell transplantation and has remained disease free to date. The CR of this patient with leukemia cutis demonstrated that CART exhibited efficacy in this case. While further research is still required, this treatment could potentially be used as a therapy for skin leukemia, lymphoma, and other primary skin cancers.


LGBTQ+ in STEM: Visibility and Beyond.
Lesbian, gay, bisexual, trans, queer (LGBTQ+, "+"=plus other sexes, gender identities, and sexual orientation) people in the STEM fields (STEM=science, technology, engineering, and mathematics) continue to experience discrimination in their workplace. In the last decade, the clamor for safe and diverse spaces continue to rise. Indeed, social media plays a huge part on increasing visibility of the LGBTQ+ community in STEM. LGBTQ+ scientists have not only promoted discourse and raised concerns to the online community, but more importantly, supported each other in platforms such as Twitter. Beyond social media, work at the institutes by LGBTQ+ individuals are also bearing fruit. This piece explores the grassroots work of scientists as they work hand-in-hand with their institute staff and leadership to promote diversity and inclusivity within and beyond their community.


Offspring sex ratios among male tobacco smokers in Khartoum, Sudan.
To explore any association between paternal tobacco smoking and the offspring secondary sex ratio, as well as the effect of duration and intensity of smoking on gender ratio. The cross-sectional study was conducted around major public areas within Khartoum, Sudan, between August and September 2008 and involved 458 married Sudanese males with offsprings. The sample consisted of 111 (24.2%) smokers and 347 (75.8%) non-smokers who were evaluated using a questionnaire on their offspring gender. Data on duration and intensity of smoking was also collected from the smokers' group. SPSS 16 was used for statistical purposes. Chi-square test was used to test for significance of associations between variables. Analysis of variance (ANOVA) was used to test for significance between ratios. The number of cigarettes smoked in males increases the likelihood of having a male offspring. The gender ratio in non-smokers was 1.11, while it was 1.15 in smokers. Paternal smoking increases the offspring sex ratio.


Solenoxyphus Reuter, 1875 (Hemiptera: Heteroptera: Miridae: Phylinae): revised diagnosis, a new species and new generic synonym.
Solenoxyphus kazakhstanicus sp. n. is described from the vicinity of Dzhezkazgan, Western Kazakhstan. The generic name Voruchia Reuter, 1879 is synonymized with Solenoxyphus Reuter, 1875. Illustrations of the male and female genitalia, photographs of the dorsal habitus, host, and distributional records are given for the new species and S. vittiger comb. nov., the type species of Voruchia. Female genitalia of Solenoxyphus and Boopidocoris spp. are studied for the first time and an updated generic diagnosis of the former genus is provided. The placement of both genera within the tribe Nasocorini sensu Schuh & Menard (2013) is briefly discussed.


CMOS-compatible compact optical isolator based on space-time modulated coupled resonators.
This work shows how phase-shifted time-modulations applied to two or more near-field coupled resonators can be engineered to achieve magnet-free optical isolation in a compact footprint. Because of the strong light-matter interaction afforded by high quality factor resonant cavities, only modest modulation amplitudes are required. A coupled mode theory model is developed which is subject to simulated annealing to optimize device performance. Then it is shown via finite-difference time-domain simulation how the device may be implemented in a one dimensional photonic crystal geometry etched in a silicon ridge waveguide. These devices can be implemented in native silicon with standard electrical contacts thereby maintaining CMOS-compatible fabrication without the need for additional specialized materials. Isolation ratios of over 40 dB with insertion loss less than 1 dB using modulation frequencies under 25 GHz are achievable in this device platform.


Synthesis of Highly Substituted Biaryls by the Construction of a Benzene Ring via In Situ Formed Acetals.
Herein, we present an interesting method for the construction of a benzene ring using propargylic alcohols and 1,3-dicarbonyls, which involves three new C-C bond formations via cascade alkylation, formylation, annulation, and aromatization to make substituted biaryls. This one-pot Brønsted acid-promoted protocol utilizes the unique reactivity of the acetal formed under the reaction conditions. Alkynyl methyl ketones could be employed instead of 1,3-dicarbonyls as they are converted to 1,3-dicarbonyls by hydration under the reaction conditions.


Microfluorometric immunoassays with antigens bound to sepharose beads.
Sepharose beads, to which protein had been coupled, were used in the development of two types of microfluorometric immunoassays. The first is an inhibition assay: a fixed amount of antiserum was absorbed with different amounts of antigen. This was accomplished in both direct and indirect incubation schemes. The system has been studied with human IgG and mouse IgM as an example. The second is a competition assay: fluorescein-labeled ovalbumin competea with unlabeled unlabeled ovalbumin for the binding sites of a rabbit antiovalbumin. This antiovalbumin was not bound directly to Sepharose but to Sepharose-coupled ovalbumin. In the indirect fluorescence inhibition and the competition assay, the sensitivity levels were determined. They proved to be the same, namely, 25 ng. This means that these fluorescence immunoassays are 10 times less sensitive than conventional radioimmunoassays and 10 times more sensitive than conventional single radial immunodiffusion.


Analysis of Friction Noise Mechanism in Lead Screw System of Autonomous Vehicle Seats and Dynamic Instability Prediction Based on Deep Neural Network.
This study investigated the squeal mechanism induced by friction in a lead screw system. The dynamic instability in the friction noise model of the lead screw was derived through a complex eigenvalue analysis via a finite element model. A two degree of freedom model was described to analyze the closed solutions generated in the lead screw, and the friction noise sensitivity was examined. The analysis showed that the main source of friction noise in the lead screw was the bending mode pair, and friction-induced instability occurred when the ratio of the stiffness of the bending pair modes was 0.9-1. We also built an architecture to predict multiple outputs from a single model using deep neural networks and demonstrated that friction-induced instability can be predicted by deep neural networks. In particular, instability with nonlinearity was predicted very accurately by deep neural networks with a maximum absolute difference of about 0.035.


The neutrophil dynamic mass redistribution assay as a medium throughput primary cell screening assay.
In a typical GPCR drug discovery campaign, an in vitro primary functional screening assay is often established in a recombinant system over-expressing the target of interest which offers advantages with respect to overall throughput and robustness of compound testing. Subsequently, compounds are then progressed into more physiologically relevant but lower throughput ex vivo primary cell assays and finally in vivo studies. Here we describe a dynamic mass redistribution (DMR) assay which has been developed in a format suitable to support medium throughput drug screening in primary human neutrophils. Neutrophils are known to express both CXCR1 and CXCR2 chemokine receptors that are thought to play significant roles in various inflammatory disorders and cancer. Using multiple relevant chemokine ligands and a range of selective and non-selective small and large molecule antagonists that block CXCR1 and CXCR2 responses, we demonstrate distinct pharmacological profiles in neutrophil DMR from those observed in recombinant assays but predictive of activity in neutrophil chemotaxis and CD11b upregulation, a validated target engagement marker previously utilized in clinical studies of CXCR2 antagonists. The primary human neutrophil DMR cell system is highly reproducible, robust, and less prone to donor variability observed in CD11b and chemotaxis assays and thus provides a unique, more physiologically relevant, and higher throughput assay to support drug discovery and translation to early clinical trials. Significance Statement Neutrophil dynamic mass redistribution assays provide a higher throughput screening assay to profile compounds in primary cells earlier in the screening cascade enabling a higher level of confidence in progressing the development of compounds towards the clinic. This is particularly important for chemokine receptors where redundancy contributes to a lack of correlation between recombinant screening assays and primary cells, with the co-expression of related receptors confounding results.


3D Printing Assisted Fabrication of Copper-Silver Mesoporous Bioactive Glass Nanoparticles Reinforced Sodium Alginate/Poly(vinyl alcohol) Based Composite Scaffolds: Designed for Skin Tissue Engineering.
Additive manufacturing (also known as 3D printing) is a promising method for producing patient-specific implants. In the present study, sodium alginate (Na-ALG)/poly(vinyl alcohol) (PVA) polymer blends of varying ratios (1:0, 3:1, 1:1, and 1:3) were used to produce tailored-designed skin scaffolds using a 3D bioprinter. Samples of skin scaffolds were printed at 20 layers with a layer height of 0.15 mm using a needle with an inner diameter of 330 μm while maintaining the extrusion speed, extrusion width, and fill density at 10 mm/s, 0.2 mm, and 85%, respectively. The Na-ALG/PVA blend with a 3:1 ratio showed the best printability due to its good viscosity and minimal nozzle leakage, allowing for the fabrication of skin scaffolds with high fidelity and the desired morphological characteristics. Then, copper-silver doped mesoporous bioactive glass nanoparticles (Cu-Ag MBGNs) were incorporated into the Na-ALG/PVA blend (which had already been prepared by using a Na-ALG:PVA ratio of 3:1) in order to obtain therapeutic (angiogenic and antibacterial) effects. The fabricated Na-ALG/PVA/Cu-Ag MBGNs biocomposite scaffolds with dimensions of 20 mm× 20 × 3 mm3 and pore size of 400 ± 60 μm exhibited a promising fidelity. The presence of chemical bonds attributed to Na-ALG, PVA, and Cu-Ag MBGNs and the uniform distribution of Na, C, and O elements within the microstructure of the scaffolds were confirmed by EDX, SEM, and FTIR analyses. The scaffolds were hydrophilic and exhibited proper swelling and degradation behavior for skin tissue engineering. According to the inhibition halo test, the scaffolds exhibited strong antibacterial activity against Staphylococcus aureus and Escherichia coli. The cytocompatibility to human-derived fibroblast cells was confirmed by the WST-8 assay and in vivo Chorioallantoic Membrane Assay. In addition, Na-ALG/PVA/Cu-Ag MBGNs showed angiogenic potential, exhibiting favorable wound healing properties.


Aptamer-facilitated cryoprotection of viruses.
Global vaccination and gene therapy programs have an urgent demand for stabilization of viral vectors at low temperature. We used a quadramer, a bridge-connected DNA tetra-aptamer to antivesicular stomatitis virus (VSV), as a viral cryoprotectant. Results showed that the tetravalent antivirus DNA aptamers protect viral activity during multiple freeze-thaw cycles, shield from neutralizing antibodies, and decrease aggregation of viral particles.


OUTCROSSING RATE AND INBREEDING DEPRESSION IN TWO ANNUAL MONOECIOUS HERBS, BEGONIA HIRSUTA AND B. SEMIOVATA.
Most models of mating-system evolution predict inbreeding depression to be low in inbred populations due to the purging of deleterious recessive alleles. This paper presents estimates of outcrossing rates and inbreeding depression for two highly selfing, monoecious annuals Begonia hirsuta and B. semiovata. Outcrossing rates were estimated using isozyme polymorphisms, and the magnitude of inbreeding depression was quantified by growing progeny in the greenhouse produced through controlled selfing and outcrossing. The estimated single-locus outcrossing rate was 0.03 ± 0.01 (SE) for B. hirsuta and 0.05 ± 0.02 for B. semiovata. In both species, the seed production of selfed flowers was on average 12% lower than that of outcrossed flowers (B. hirsuta P = 0.07, B. semiovata P < 0.05, mixed model ANOVAs). There was no significant effect of crosstype on germination rate or survival, but selfed offspring had a lower dry mass than outcrossed offspring 18 weeks after planting in both species (on average 18% lower in B. hirsuta and 31% lower in B. semiovata). Plants that were the products of selfing began flowering later than plants produced through outcrossing in B. semiovata, but not in B. hirsuta. The effects of crosstype on seed production (B. semiovata), days to first flower and offspring dry mass (both species) varied among maternal parents, as indicated by significant crosstype x maternal parent interactions for these characters. Both species showed significant inbreeding depression for total fitness (estimated as the product of seed production, germination rate, survival and dry mass at 18 weeks). In B. hirsuta, the average total inbreeding depression was 22% (range -57%-98%; N = 23 maternal parents), and in B. semiovata, it was 42% (-11%-84%; N = 21). This study demonstrates that highly selfing populations can harbor substantial inbreeding depression. Our findings are consistent with the hypothesis that a high mutation rate to mildly deleterious alleles contributes to the maintenance of inbreeding depression in selfing populations.


Psychotherapy for depression: a randomized clinical trial comparing schema therapy and cognitive behavior therapy.
The efficacy of Cognitive Behavior Therapy (CBT) for depression has been robustly supported, however, up to fifty percent of individuals do not respond fully. A growing body of research indicates Schema Therapy (ST) is an effective treatment for difficult and entrenched problems, and as such, may be an effective therapy for depression. In this randomized clinical trial the comparative efficacy of CBT and ST for depression was examined. 100 participants with major depression received weekly cognitive behavioral therapy or schema therapy sessions for 6 months, followed by monthly therapy sessions for 6 months. Key outcomes were comparisons over the weekly and monthly sessions of therapy along with remission and recovery rates. Additional analyses examined outcome for those with chronic depression and comorbid personality disorders. ST was not significantly better (nor worse) than CBT for the treatment of depression. The therapies were of comparable efficacy on all key outcomes. There were no differential treatment effects for those with chronic depression or comorbid personality disorders. This study needs replication. This preliminary research indicates that ST may provide an effective alternative therapy for depression.