Percutaneous Endoscopic Interlaminar Discectomy for L5-S1 Adolescent Lumbar Disc Herniation.
L5/S1 Adolescent lumbar disc herniation (ALDH) is usually ignored for its low incidence. Recently, percutaneous endoscopic procedures have been widely used. To investigate the surgical techniques and clinical outcomes of percutaneous endoscopic interlaminar discectomy (PEID) in the treatment of adolescent L5-S1 disc herniation (ALDH). A retrospective study was performed between May 2012 and September 2014, which included 23 adolescent patients who underwent PEID for L5/S1 lumbar disc herniation. Ten females and 13 males were included, with a mean age of 15.4 years and a mean BMI of 25.1 kg/m2. The pre- and postoperative visual analogue scale (VAS), Japanese Orthopaedic Association (JOA), and modified MacNab scores, as well as perioperative data, were collected. The mean follow-up period was 19.7 months. The average operation time and hospital stay were 80.9 ± 7.3 minutes and 5.8 ± 1.2 days, respectively. During the follow-up period, the VAS for back and leg pain decreased significantly, and JOA scores greatly increased (p < 0.05). In terms of modified MacNab criteria, 86.9% of patients showed excellent or good results. After surgery, two patients complained of leg numbness, and another patient underwent a subsequent open discectomy due to recurrent disc herniation. Considering specific anatomical peculiarities and expectation for rapid recovery, PEID is a safe and effective minimally invasive technique for ALDH at the L5-S1 level.


Color and luminance increment thresholds in poor readers.
The hypotheses of a visual basis to reading disabilities in some children have centered around deficits in the visual processes displaying more transient responses to stimuli although hyperactivity in the visual processes displaying sustained responses to stimuli has also been proposed as a mechanism. In addition, there is clear evidence that colored lenses and/or colored overlays and/or colored backgrounds can influence performance in reading and/or may assist in providing comfortable vision for reading and, as a consequence, the ability to maintain reading for longer. As a consequence, it is surprising that the color vision of poor readers is relatively little studied. We assessed luminance increment thresholds and equi-luminous red-green and blue-yellow increment thresholds using a computer based test in central vision and at 10 degrees nasally employing the paradigm pioneered by King-Smith. We examined 35 poor readers (based on the Neale Analysis of Reading) and compared their performance with 35 normal readers matched for age and IQ. Poor readers produced similar luminance contrast thresholds for both foveal and peripheral presentation compared with normals. Similarly, chromatic contrast discrimination for the red/green stimuli was the same in normal and poor readers. However, poor readers had significantly lower thresholds/higher sensitivity for the blue/yellow stimuli, for both foveal and peripheral presentation, compared with normal readers. This hypersensitivity in blue-yellow discrimination may point to why colored lenses and overlays are often found to be effective in assisting many poor readers.


Exploring the experiences of mental health professionals engaged in the adoption of mobile health technology in Irish mental health services.
The World Health Organization report that an estimated 793,000 people died by suicide in 2016 globally. The use of digital technology has been found to be beneficial in the delivery of Web-based suicide prevention interventions. Research on the integration of digital technology within mental health services has indicated that despite the proliferation of technology, engagement by patients and professionals in adopting such technology can be poor. The current study aims to explore the experiences of 15 mental health professionals involved in integrating mobile health technology into their practice. A secondary aim was to identify the drivers and barriers to the adoption of such technology by mental health professionals, and to consider what theoretical models could best account for the data. Semi-structured interviews, conducted from July to October 2019, were used to explore the experiences of mental health professionals engaged in the adoption of mobile health technology within mental health services. Mental Health professionals and clinician managers working in HSE Child and Adolescent Mental Health, Adult Mental Health, and Primary Care Psychology services were recruited for the study. Qualitative interview data was transcribed and analysed using NVivo. Thematic Analysis was used to identify themes. Four major themes were identified: Accessibility, 'Transitional Object', Integration, and Trust. Within these 4 major themes, a total of 9 subthemes were identified: Service Accessibility, Immediate Access, Client Engagement, Adjunct-to-therapy, Therapeutic Relationship, Infrastructural Support, Enhancing Treatment, Trust in the Technology, Trust in the Organisation. Overall, Diffusion of Innovation Theory provides a useful theoretical framework which is consistent with and can adequately account for many of the Major and Subthemes identified in the data. In addition, 'Transitional Objects', a key concept within Object Relations Theory, could offer a means of better understanding how patients and professionals engage with digital technology within mental health services particularly.


Between the idea and the reality: GP liaison in a rural setting.
To describe the organisational, clinical and pragmatic features of a GP liaison service established by the Division of Mental Health in the Darling Downs Hospital and Health Service catchment to facilitate the care of rural patients and improve communication between primary and specialist care. The GP liaison service was created using funding from the Commonwealth STP initiative to provide weekly registrar clinics to primary care providers in the Darling Downs. The service was eagerly accepted by providers who saw patient benefits outweighing financial considerations. Expectations of a greater level of care than the assessment and advice provided reflects the large unmet need for mental health services in rural areas. GPs expressed enthusiasm for true collaborative care, such as case management overseen by the public mental health service but based at GP offices.


CHIP Decline Is Associated With Isoflurane-Induced Neurodegeneration in Aged Mice.
Perioperative neurocognitive disorders (PND) commonly occur in elderly patients, and isoflurane could be a risk factor. During the pathogenesis of neurodegeneration, the ubiquitin-proteasome system (UPS) participates in the process of aging, which affects synaptic plasticity and synaptic function. However, whether UPS is involved in the etiology of PND is unclear. In this study, we examined the expression change of ubiquitin E3 ligase protein carboxyl-terminus of Hsc70-interacting protein (CHIP) and the function turbulence of UPS in isoflurane-exposed aged mouse to illustrate the role of UPS in PND. Neurodegenerative behavioral changes were shown in isoflurane-exposed aged mice and correlated with neuropathological changes manifested with reduced number of intersections and spine density in the cortex. Ubiquitin function was decreased while the apoptosis was activated, and CHIP protein expression decline altered synapsin expression and phosphorylation associated with the neurodegeneration in isoflurane-induced PND. Aging was the big important factor. And it remained consistent with the synapsin phosphorylation/dephosphorylation level changes in CHIP knock-down N2a cells. Per our observation, the decline in CHIP protein expression and synaptic degeneration might reveal the reason for synaptic degeneration in the underlying pathogenesis of PND caused by isoflurane.


A review of thin layer drying of foods: theory, modeling, and experimental results.
Drying is a complicated process with simultaneous heat and mass transfer, and food drying is especially very complex because of the differential structure of products. In practice, a food dryer is considerably more complex than a device that merely removes moisture, and effective models are necessary for process design, optimization, energy integration, and control. Although modeling studies in food drying are important, there is no theoretical model which neither is practical nor can it unify the calculations. Therefore the experimental studies prevent their importance in drying and thin layer drying equations are important tools in mathematical modeling of food drying. They are practical and give sufficiently good results. In this study first, the theory of drying was given briefly. Next, general modeling approaches for food drying were explained. Then, commonly used or newly developed thin layer drying equations were shown, and determination of the appropriate model was explained. Afterwards, effective moisture diffusivity and activation energy calculations were expressed. Finally, experimental studies conducted in the last 10 years were reviewed, tabulated, and discussed. It is expected that this comprehensive study will be beneficial to those involved or interested in modeling, design, optimization, and analysis of food drying.


Challenges of smokeless tobacco use in Myanmar.
Myanmar Tobacco Control Law of 2006 covers the control of all forms of tobacco use. After 7-year, tobacco use among adults did not see a decrease. The paper aimed to study the prevalence, details of the products, trade, legislation, tax, marketing, advertising and evidence on morbidity and mortality, and to make recommendations for policy options. Personal communications by authors and colleagues, and searches by keywords in PubMed and on Google, literature review and research from published reports, and various studies and surveys conducted in Myanmar and other countries. Smokeless tobacco use in Myanmar is the highest among ASEAN countries. A variety of SLT products used together with betel chewing poses a challenge; betel quid chewing has been accepted as a cultural norm in both rural and urban areas. Betel quid chewing usually starts at younger ages. Sale, marketing, and advertising of SLT are not under control and thus, road-side kiosks selling betel quid with SLT are mushrooming. Considerable trade of SLT products by illegal and legal means created an increase in access and availability. Low cost of SLT product enables high volume of use, even for the poor families. Taxation for raw tobacco and tobacco products is half the values of the tax for cigarettes. Effective enforcement, amendment of the law, and action for social change are needed.


Availability of primary care team members can improve teamwork and readiness for change.
Early experiences of patient-centered medical home implementation indicate that redesigning primary care is an intensive organizational change that is most effectively undertaken by high-functioning interdisciplinary teams. Team effectiveness research indicates that consistent availability of team members and other aspects of team structure can impact teamwork and organizational outcomes. We conducted a survey of 766 adult primary care providers and staff in 34 California safety net practices to assess primary care team structure (team size, team member availability, and access to interdisciplinary expertise), teamwork, and readiness for change. We used path models with robust standard errors for clustering of respondents within practices to examine relationships between team member availability and readiness for change. Using path analysis, we examined the extent to which better teamwork mediated relationships between team member availability and readiness for change. We received 628 completed surveys (response rate = 82%). Greater team member availability was associated with greater readiness for change, but the relationship was stronger for staff than for primary care providers. Contrary to our hypothesis, path analyses revealed that the relationship of team member availability and greater readiness for change was only partially mediated (21%) by better teamwork. The direct effect of teamwork on readiness for change is approximately 2.9 times larger than the direct effect of team member availability on greater readiness for change. Ensuring that members perceive that their teammates are routinely available to them may improve readiness for implementing organizational changes like adopting patient-centered medical home models. Given that better teamwork only partially explained the availability-readiness relationship, additional research to identify the mechanisms through which consistent team member availability increases change readiness could lend insight into how to more effectively support clinicians and staff undergoing complex organizational changes.


Effect of skin fibroblast-derived allogeneic feeder cells on porcine ES-like cell establishment.
In the present study, the effect of two types of allogeneic-derived feeder cells [porcine ear and tail skin fibroblasts (PESF, PTSF)] and three types of xenogeneic-derived feeder cells [human foreskin fibroblasts (HFK), mouse embryonic fibroblasts (MEF) and immortalized mouse embryonic fibroblasts (STO)] on the isolation and cultivation of putative porcine embryonic stem cells (pESCs) was evaluated. In vivo derived zona pellucida (ZP)-free blastocysts were cultured on different mitotically inactivated feeder layers. The rates of ICM outgrowth and primary colony formation were observed, and further passage onto new feeders was performed. The characteristics of pESCs, including alkaline phosphatase (AP) activity, and pluripotent-related markers (OCT3/4, NANOG, SSEA-4) and genes were examined. Attached blastocysts cultured on HFK and STO feeders showed a higher percentage of ICM outgrowths than those cultured on PESF (76.7, 72.9 and 38.9%, respectively; P<0.05). The rates of primary ES-like colony formation and the number of putative ESC lines were significantly decreased when ICM outgrowths were cultured on PESF, compared with those cultured on HFK (30.6 vs. 76.7%, respectively; P<0.05). Only ES-like colonies from one (25%) and three (50%) cell lines developed on PTSF and STO feeders, respectively, were further maintained in an undifferentiated morphology associated with the presence of all ES characteristics; however, these characteristics disappeared when colonies were continued to the 8th and 6th passages, respectively. The present study indicated that feeder cell types affect the success of pESC establishment and maintenance of their pluripotency.


Allostatic Load and Effort-Reward Imbalance: Associations over the Working-Career.
Although associations between work stressors and stress-related biomarkers have been reported in cross-sectional studies, the use of single time measurements of work stressors could be one of the reasons for inconsistent associations. This study examines whether repeated reports of work stress towards the end of the working career predicts allostatic load, a measure of chronic stress related physiological processes. Data from waves 2 to 6 of the English Longitudinal Study of Ageing (ELSA) were analysed, with a main analytical sample of 2663 older adults (aged 50+) who had at least one measurement of effort-reward imbalance between waves 2-6 and a measurement of allostatic load at wave 6. Cumulative work stress over waves 2-6 were measured by the effort-reward imbalance model. ELSA respondents who had reported two or more occasions of imbalance had a higher (0.3) estimate of the allostatic load index than those who did not report any imbalance, controlling for a range of health and socio-demographic factors, as well as allostatic load at baseline. More recent reports of imbalance were significantly associated with a higher allostatic load index, whereas reports of imbalance from earlier waves of ELSA were not. The accumulation of work related stressors could have adverse effects on chronic stress biological processes.


Revisiting mechanisms of resistance to immunotherapies in metastatic clear-cell renal-cell carcinoma.
Renal-cell carcinoma (RCC) remains a leading cause of cancer-related mortality worldwide. Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes, resistance to these therapies is becoming a challenge for long-term control. Mechanisms of resistance have been explored in a variety of solid tumors, including RCC. Based upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas (mccRCC), the ensuing conclusions have been made: The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies, alone and/or in combination. Nevertheless, innate or developed resistance to these therapies remains an ongoing challenge, particularly to immune checkpoint inhibitors (ICIs). Several of the known mechanisms of resistance have been well defined, but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal disease. In the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC, we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.


Postpartum Spinal Epidural Lipomatosis With Epidural Venous Engorgement.
Spinal epidural lipomatosis (SEL) refers to a condition characterized by the abnormal growth of fatty tissue within the vertebral canal, situated outside the spinal canal itself. This expansion of fat can result in symptoms such as back pain and radiculopathy. The majority of cases remain without noticeable symptoms. However, when SEL does cause symptoms, it is frequently linked to using external steroids. The contributing factors to SEL include obesity and Cushing's syndrome. The presentation of SEL can mimic other spinal disorders such as epidural hematoma, spinal stenosis, and degenerative joint disease. Patients might present with gradually progressing and long-standing complaints of back pain, muscle weakness, numbness, loss of bladder or bowel control, lack of coordination, abnormal reflexes, and, in rare instances, paralysis. We are reporting a case involving a 34-year-old female with obesity, who experienced sudden weakness in her left lower extremity shortly after a recent uncomplicated vaginal delivery using epidural analgesia. A magnetic resonance imaging (MRI) of her thoracic (T) and lumbar spine revealed spinal cord compression secondary to extensive posterior epidural lipomatosis associated with epidural venous engorgement. The patient underwent an immediate laminectomy procedure at the T3, T5, T7, and T9 levels to alleviate the compression. Postoperatively, she underwent a course of physiotherapy and gradually regained her normal muscle strength. She was discharged in stable condition on the sixth day after the surgery.


Epithelioid Inflammatory Myofibroblastic Sarcoma With Poor Response to Crizotinib: A Case Report.
Epithelioid type inflammatory myofibroblastic sarcoma (EIMS) is a subtype of inflammatory myofibroblastic tumor (IMT). It consists of round or epithelioid cells, and almost all types of EIMS contain rearrangements of the anaplastic lymphoma kinase (ALK) gene. We describe a 20-year-old female presenting with abdominal pain and a rapidly growing intraabdominal mass who underwent surgical tumor resection. She was diagnosed with EIMS. ALK and ki-67 expressions were detected in immunohistochemistry assessment. She was started with Crizotinib 200 mg twice a day, and chemotherapy was also initiated due to the recurrence of the disease 4 months after the initial treatment. She was unresponsive to all the medical regimens and died in 8 months. Approach to patients with EIMS is really challenging in terms of both diagnosis and treatment. Patients with combined surgical and non-surgical treatment regimen were seen to have a more favorable outcome in some EIMS cases. Therefore, it is essential to implement a multidisciplinary approach to diagnose and treat patients suspicious of EIMS.


Attachment Theory and Psychotherapy Research - Editor's Introduction to a Special Section.
This article introduces the special section dealing with research on attachment and psychotherapy. Although John Bowlby conceptualized his theory as a tool for clinicians to acquire a better understanding of the development of psychopathology and emotional distress, it took a long time until clinical researchers started to make use of Bowlby's theory. During the last decade, a large number of studies have been published showing that attachment theory could be very useful within different fields of psychotherapy research, such as differentiating psychopathology, therapist characteristics, and aspects of the therapeutic alliance. These fields are briefly stressed and related to the articles in the special section emphasizing some future directions of attachment response within psychotherapy.


Clostridium difficile infection in a French university hospital: Eight years of prospective surveillance study.
The epidemiology of Clostridium difficile infection (CDI) has changed with an increase in incidence and severity. Prospective surveillance was therefore implemented in a French university hospital to monitor the characteristics of patients at risk and to recognize local trends. Between 2007 and 2014, all hospitalized patients (≥18 years) with CDI were included. During the survey, the mean incidence rate of CDI was 2.9 per 10,000 hospital-days. In all, 590 patients were included. Most of the episodes were healthcare-associated (76.1%). The remaining cases were community-acquired (18.1%) and unknown (5.9%). The comparison with healthcare-associated cases showed that the community-acquired group had a lower rate of antimicrobial exposure (P < 0.001), proton pump inhibitor (P < 0.001), and immunosuppressive drugs (P = 0.02). Over the study period, death occurred in 61 patients (10.3%), with 18 (29.5%) being related to CDI according to the physician in charge of the patient. Active surveillance of CDI is required to obtain an accurate picture of the real dimensions of CDI.


Coupling specificity between somatostatin receptor sst2A and G proteins: isolation of the receptor-G protein complex with a receptor antibody.
Somatostatin initiates its actions via a family of seven-transmembrane domain receptors. Of the five somatostatin receptor genes cloned, sst2 exists as two splice variants with the sst2A isoform being predominantly expressed. This receptor is widely distributed in endocrine, exocrine, and neuronal cells, as well as in hormonally responsive tumors, and leads to inhibition of secretion, electrical excitability, and cell proliferation. To investigate the specificity of signal transduction by the sst2A receptor, we developed antibodies against two overlapping peptides located within the C terminus of the receptor protein: peptide 2C(SG), containing amino acids 334-348, and peptide 2C(ER), containing amino acids 339-359. Although antibodies to both peptides bound the inducing antigen with high affinity, only the antibodies against peptide 2C(ER) precipitated the receptor. The best antibody, R2-88, precipitated about 80% of the sst2A receptor-ligand complex solubilized from transfected CHO cells and was specific for the sst2A receptor isotype. Addition of GTPgammaS (10 microM) to the immunoprecipitated ligand-sst2A receptor complex markedly accelerated ligand dissociation, indicating that G proteins remained functionally associated with the receptor in the immunoprecipitate. Analysis of the G proteins coprecipitated with the sst2A receptor by immunoblotting with G protein antibodies showed that both G(alpha) and G(beta) subunits were bound to the hormone-receptor complex. Immunoprecipitation of the receptor was not affected by the presence of bound ligand. However, G protein subunits were coprecipitated only with the hormone-occupied receptor. Thus, the unoccupied receptor has low affinity for G proteins, and hormone binding stabilizes the receptor-G protein complex. Use of subtype-specific G protein antisera further showed that G alpha(i1), G alpha(i2), and G alpha(i3) were complexed with the sst2A receptor whereas Galpha(o), G alpha(z), and G alpha(q) were not. Together, these studies demonstrate that the sst2A receptor interacts selectively with G alpha(i) proteins in a hormone-dependent manner. The finding that this receptor couples to all three G alpha(i) subunits may help explain how somatostatin can regulate multiple signaling pathways.


Crystal structure and functional characterization of an isoaspartyl dipeptidase (CpsIadA) from Colwellia psychrerythraea strain 34H.
Isoaspartyl dipeptidase (IadA) is an enzyme that catalyzes the hydrolysis of an isoaspartyl dipeptide-like moiety, which can be inappropriately formed in proteins, between the β-carboxyl group side chain of Asp and the amino group of the following amino acid. Here, we have determined the structures of an isoaspartyl dipeptidase (CpsIadA) from Colwellia psychrerythraea, both ligand-free and that complexed with β-isoaspartyl lysine, at 1.85-Å and 2.33-Å resolution, respectively. In both structures, CpsIadA formed an octamer with two Zn ions in the active site. A structural comparison with Escherichia coli isoaspartyl dipeptidase (EcoIadA) revealed a major difference in the structure of the active site. For metal ion coordination, CpsIadA has a Glu166 residue in the active site, whereas EcoIadA has a post-translationally carbamylated-lysine 162 residue. Site-directed mutagenesis studies confirmed that the Glu166 residue is critical for CpsIadA enzymatic activity. This residue substitution from lysine to glutamate induces the protrusion of the β12-α8 loop into the active site to compensate for the loss of length of the side chain. In addition, the α3-β9 loop of CpsIadA adopts a different conformation compared to EcoIadA, which induces a change in the structure of the substrate-binding pocket. Despite CpsIadA having a different active-site residue composition and substrate-binding pocket, there is only a slight difference in CpsIadA substrate specificity compared with EcoIadA. Comparative sequence analysis classified IadA-containing bacteria and archaea into two groups based on the active-site residue composition, with Type I IadAs having a glutamate residue and Type II IadAs having a carbamylated-lysine residue. CpsIadA has maximal activity at pH 8-8.5 and 45°C, and was completely inactivated at 60°C. Despite being isolated from a psychrophilic bacteria, CpsIadA is thermostable probably owing to its octameric structure. This is the first conclusive description of the structure and properties of a Type I IadA.


Amylolysis of a chromogenic substrate, Cibachron Blue F3GA-amylose: kinetics and mechanism.
We compared the modes of action of human pancreatic, human salivary, and porcine pancreatic amylases on Cibachron Blue F3GA-amylose. Both human enzymes showed similar catalytic activity with almost equal Vmax but dissimilar apparent Km's. The ratios of soluble dyed oligosaccharides to reducing substances were identical. Porcine pancreatic amylase exhibited less than half the Vmax of the human enzymes and a smaller apparent Km. Reducing substances were formed faster than were the soluble dyed products. These differences in amylolytic action can be explained by differences in the degree of the "multiple attack" mechanism. Introduction of dye substituents into the amylose molecule did not alter the substrate characteristics of amylose toward human serum amylase.


Chromium Morpho-Phytotoxicity.
Chromium (Cr) is considered as one of the chronic pollutants that cause damage to all living forms, including plants. Various industries release an excessive amount of Cr into the environment. The increasing accumulation of Cr in agricultural land causes a significant decrease in the yield and quality of economically important crops. The Cr-induced biochemical, molecule, cytotoxic, genotoxic, and hormonal impairments cause the inhibition of plant growth and development. In the current study, we reviewed Cr morpho-phytotoxicity related scientific reports published between 2009 to 2019. We mainly focused on the Cr-induced inhibition of seed germination and total biomass production. Furthermore, Cr-mediated reduction in the root, branches, and leave growth and development were separately discussed. The Cr uptake mechanism and interference with the macro and micro-nutrient uptake were also discussed and visualized via a functional model. Moreover, a comprehensive functional model has been presented for the Cr release from the industries, its accumulation in the agricultural land, and ultimate morpho-phytotoxicity. It is concluded that Cr-reduces plant growth and development via its excess accumulation in the plant different parts and/or disruption of nutrient uptake.


The Association Between Political Violence and the Connection Between Bullying and Suicidality Among Palestinian Youth.
We examined the association between protracted political violence and the connection between bullying and suicidality among Palestinian adolescents. Data were collected from a representative sample of Palestinian students (N = 5,713) from 100 schools in the West Bank and East Jerusalem who completed an in-class survey. Students who were victims of bullying or bully victims who were exposed to political violence were at higher risk for suicide attempts compared to students who were victims of bullying or bully victims but not exposed to political violence. Political violence moderated the association between bullying and suicide attempts after controlling for socio demographic and other mental health variables.


Right occipital transtentorial approach for a pineal malignant germ cell tumor.
Germ cell tumors account for up to 53% of the malignant lesions found in the pineal region and are typically managed with a combination of radiation therapy and chemotherapy. Malignant somatic transformation of intracranial germ cell tumors is exceedingly rare and has only been reported on two other occasions. Here the authors present the case of a pineal yolk sac tumor that failed optimum first-line treatment and underwent malignant somatic transformation to an enteric mucinous adenocarcinoma requiring surgical intervention. This video demonstrates the technical nuances of the occipital transtentorial approach and the safe microsurgical dissection of lesions within the pineal region. The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID2151.


Intertrochanteric varus osteotomy for osteoarthritis in patients with hip dysplasia: 6 to 28 years followup.
There have been few reports regarding midterm to long-term results of intertrochanteric varus osteotomy for treatment of hip dysplasia. We investigated 55 hips in 46 patients, with an average age at surgery of 32 years (range, 12-55 years), for an average followup of 17 years (range, 6-28 years). Preoperative osteoarthritis was Tonnis Grade 0 in seven hips, Grade 1 in 23 hips, Grade 2 in 21 hips, and Grade 3 in four hips. Preoperative anteroposterior radiographs of the 55 hips showed almost perfect congruency between the acetabulum and the femoral head with the hip in an abducted position. Excellent or good clinical results were obtained in 23 hips (42%). Using a Harris hip score less than 70 points or the time until additional surgery as the end point, the cumulative rates of survival were 81% at 10 years, 60% at 20 years, and 50% at 25 years. The clinical results of patients with Grade 0, 1, or 2 osteoarthritis, with good spherical femoral head and mild dysplasia, were acceptable; however, this osteotomy might not be indicated for patients with Grade 3 osteoarthritis or for those with severe acetabular dysplasia. Therapeutic study, Level IV (case series--no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.


Complexation of lysozyme with adsorbed PtBS-b-SCPI block polyelectrolyte micelles on silver surface.
We present a study of the interaction of the positively charged model protein lysozyme with the negatively charged amphiphilic diblock polyelectrolyte micelles of poly(tert-butylstyrene-b-sodium (sulfamate/carboxylate)isoprene) (PtBS-b-SCPI) on the silver/water interface. The adsorption kinetics are monitored by surface plasmon resonance, and the surface morphology is probed by atomic force microscopy. The micellar adsorption is described by stretched-exponential kinetics, and the micellar layer morphology shows that the micelles do not lose their integrity upon adsorption. The complexation of lysozyme with the adsorbed micellar layers depends on the micelles arrangement and density in the underlying layer, and lysozyme follows the local morphology of the underlying roughness. When the micellar adsorbed amount is small, the layers show low capacity in protein complexation and low resistance in loading. When the micellar adsorbed amount is high, the situation is reversed. The adsorbed layers both with or without added protein are found to be irreversibly adsorbed on the Ag surface.


Artificial intelligence to identify genetic alterations in conventional histopathology.
Precision oncology relies on the identification of targetable molecular alterations in tumor tissues. In many tumor types, a limited set of molecular tests is currently part of standard diagnostic workflows. However, universal testing for all targetable alterations, especially rare ones, is limited by the cost and availability of molecular assays. From 2017 to 2021, multiple studies have shown that artificial intelligence (AI) methods can predict the probability of specific genetic alterations directly from conventional hematoxylin and eosin (H&E) tissue slides. Although these methods are currently less accurate than gold standard testing (e.g. immunohistochemistry, polymerase chain reaction or next-generation sequencing), they could be used as pre-screening tools to reduce the workload of genetic analyses. In this systematic literature review, we summarize the state of the art in predicting molecular alterations from H&E using AI. We found that AI methods perform reasonably well across multiple tumor types, although few algorithms have been broadly validated. In addition, we found that genetic alterations in FGFR, IDH, PIK3CA, BRAF, TP53, and DNA repair pathways are predictable from H&E in multiple tumor types, while many other genetic alterations have rarely been investigated or were only poorly predictable. Finally, we discuss the next steps for the implementation of AI-based surrogate tests in diagnostic workflows. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Increase of thiopental concentration in tissues of the rat due to an anesthesia with halothane.
In rats anesthetized with halothane (CAS 151-67-7) (1.5 vol%) and rats without any further treatment (control) the early distribution phase of thiopental (CAS 76-75-5) (i.v. 30 mg/kg) was studied. In serum and 8 tissues thiopental concentration (T) was determined using ultraviolet detection at 305 nm after extraction and TLC. In rats anesthetized with halothane, T in serum was significantly higher during the 30 min following the thiopental injection (at least +27% and maximally +51%) as compared to the control (same dose), and several pharmacokinetic parameters (e.g. central volume of distribution) were found to be changed thereby; furthermore, at 3, 10 and 30 min T was significantly increased in liver, brain, heart, lung and spleen; in kidney and skeletal muscle a rise of T was also seen, however, it occurred later (after 10 and 30 min). T in fat tissue increased time-dependently; a T-difference in adipose tissue between both groups was not observed. Thiopental was "trapped" during the early distribution phase to a considerable extent in the vessel-rich tissues of rats simultaneously anesthetized with halothane; this pharmacokinetic interaction might be explained hemodynamically: in many tissues regional blood flow is reduced by halothane; thereby a delayed "washout" of thiopental from the vessel-rich tissues could take place and redistribution would be delayed; additional factors as e.g. an increased binding of thiopental at tissue proteins could also play a role. An unusually high T was found at least temporarily in myocardial tissue due to this interaction between the two anesthetics.


[Advances in microbial production of alkaline polygalacturonate lyase and its application in clean production of textile industry].
We reviewed the microbial production of alkaline polygalacturonate lyase (PGL) and its application in the clean production of textile industry. Currently PGL is mainly produced by microbial fermentation and Bacillus sp. is an ideal wild strain for PGL production. Microbial PGL production was affected by many factors including the concentration and feeding mode of substrate, cell concentration, agitation speed, aeration rate, pH and temperature. Constructing the recombinant strain provided an effective alternative for PGL production, and the concentration of PGL produced by the recombinant Pichia pastoris reached 1305 U/mL in 10 m3 fermentor. The recombinant Pichia pastoris had the potential to reach the industrial production of PGL. PGL can be applied in bio-scouring process in the pre-treatment of cotton. Compared with the traditional alkaline cooking process, the application of PGL can protect fiber, improve the bio-scouring efficiency, decrease energy consumption and alleviate the environmental pollution. The future research focus will be the molecular directed evolution of PGL to make PGL more suitable for the application of PGL in bio-scouring process to realize the clean production of textile industry.


Validity of Simulation-Based Assessment for Accreditation Council for Graduate Medical Education Milestone Achievement.
The Accreditation Council for Graduate Medical Education requires biannual evaluation of anesthesiology residents on 25 subcompetency milestones. Some milestone domains are particularly challenging to repeatedly and reliably observe during clinical care. Simulation-Based Milestones Assessment (SBMA) may help overcome these challenges. However, few studies have examined the external validation of simulation assessment scores (ie, the relationships between simulation-based assessment scores and other standard measures of ability) for milestones. This study analyzed whether SBMA scores (1) discriminate by postgraduate year, (2) improve over time, and (3) correlate with traditional measures of performance. This is a retrospective analysis of 55 residents' SBMA data from 30 scenarios for two academic years. Each scenario was evaluated for time-in-training discrimination. Scenarios were then analyzed for SBMA scoring trends over time, and SBMA scores were compared with residents' clinical evaluations. Twenty-four SBMA scenarios discriminated by postgraduate year. Repeated measure analysis of variance showed statistically significant between-session score improvements (F (3, 54) = 17.79, P < 0.001). Pearson correlation coefficients demonstrated moderate to strong correlation between SBMA and clinical evaluations: January 2015 r = 0.67, P < 0.01 (n = 27); May 2015 r = 0.43, P = 0.09 (n = 17); November 2015 r = 0.70, P < 0.01 (n = 24); and April 2016 r = 70, P < 0.01 (n = 27). The associations between SBMA scores and experience level, time-in-training, and clinical performance evaluations provide evidence that SBMA may be used as metrics of residents' Accreditation Council for Graduate Medical Education milestone competencies.


A Case of Subclavian Artery Aneurysm with History of Ischemic Heart Disease Operated Under Cervical Epidural Anesthesia.
Subclavian artery aneurysm is usually operated under general anesthesia (GA), but in specific situations, it can also be conducted under regional anesthesia (RA) such as cervical epidural anesthesia (CEA). A 48-year-old male presented with chief complaint of progressive swelling in the right side of the neck for the past 3 months following trauma. He was diagnosed as subclavian artery aneurysm, and surgical intervention was advised. He had previous history of angina 4 months back for which tablet aspirin 75 mg and tablet clopidogrel 75 mg once daily was prescribed. Cardiological evaluation revealed of an ejection fraction of around 30% with mild left ventricular hypokinesia and grade 2 diastolic dysfunction. Due to the poor cardiac functional status of the patient, RA with CEA was planned. The risk with GA in cases with a history of myocardial ischemia is more than RA, hence, it is better to use CEA which is equally efficacious in such high-risk cases.


Incidences of Unfavorable Events in the Management of Low-Risk Papillary Microcarcinoma of the Thyroid by Active Surveillance Versus Immediate Surgery.
The incidence of papillary microcarcinoma (PMC) of the thyroid is rapidly increasing globally, making the management of PMC an important clinical issue. Excellent oncological outcomes of active surveillance for low-risk PMC have been reported previously. Here, unfavorable events following active surveillance and surgical treatment for PMC were studied. From February 2005 to August 2013, 2153 patients were diagnosed with low-risk PMC. Of these, 1179 patients chose active surveillance and 974 patients chose immediate surgery. The oncological outcomes and the incidences of unfavorable events of these groups were analyzed. In the active surveillance group, 94 patients underwent surgery for various reasons; tumor enlargement and the appearance of novel lymph node metastases were the reasons in 27 (2.3%) and six patients (0.5%), respectively. One of the patients with conversion to surgery had nodal recurrence, and five patients in the immediate surgery group had a recurrence in a cervical node or unresected thyroid lobe. All of these recurrences were successfully treated. None of the patients had distant metastases, and none died of the disease. The immediate surgery group had significantly higher incidences of transient vocal cord paralysis (VCP), transient hypoparathyroidism, and permanent hypoparathyroidism than the active-surveillance group did (4.1% vs. 0.6%, p < 0.0001; 16.7% vs. 2.8%, p < 0.0001; and 1.6% vs. 0.08%, p < 0.0001, respectively). Permanent VCP occurred only in two patients (0.2%) in the immediate surgery group. The proportion of patients on L-thyroxine for supplemental or thyrotropin (TSH)-suppressive purposes was significantly larger in the immediate surgery group than in the active surveillance group (66.1% vs. 20.7%, p < 0.0001). The immediate surgery group had significantly higher incidences of postsurgical hematoma and surgical scar in the neck compared with the active surveillance group (0.5% vs. 0%, p < 0.05; and 8.0% vs. 100%, p < 0.0001, respectively). The oncological outcomes of the immediate surgery and active surveillance groups were similarly excellent, but the incidences of unfavorable events were definitely higher in the immediate surgery group. Thus, active surveillance is now recommended as the best choice for patients with low-risk PMC.


The putative high-affinity nitrate transporter NRT2.1 represses lateral root initiation in response to nutritional cues.
Lateral root initiation is strongly repressed in Arabidopsis by the combination of high external sucrose and low external nitrate. A previously isolated mutant, lin1, can overcome this repression. Here, we show that lin1 carries a missense mutation in the NRT2.1 gene. Several allelic mutants, including one in which the NRT2.1 gene is completely deleted, show similar phenotypes to lin1 and fail to complement lin1. NRT2.1 encodes a putative high-affinity nitrate transporter that functions at low external nitrate concentrations. Direct measurement of nitrate uptake and nitrate content in the lin1 mutant seedlings established that both are indeed reduced. Because repression of lateral root initiation in WT plants can be relieved by increased concentrations of external nitrate, it is surprising to find that repression is also relieved by a defect in a component of the high-affinity nitrate uptake system. Furthermore, lateral root initiation is increased in lin1 relative to WT even when seedlings are grown on nitrate-free media, suggesting that the mutant phenotype is nitrate-independent. These results indicate that NRT2.1 is a repressor of lateral root initiation and that this role is independent of nitrate uptake. We propose that Arabidopsis NRT2.1 acts either as a nitrate sensor or signal transducer to coordinate the development of the root system with nutritional cues.


Dual-basis analytic gradients. 1. Self-consistent field theory.
Analytic gradients of dual-basis Hartree-Fock and density functional theory energies have been derived and implemented, which provide the opportunity for capturing large basis-set gradient effects at reduced cost. Suggested pairings for gradient calculations are 6-31G/6-31G**, dual[-f,-d]/cc-pVTZ, and 6-311G*/6-311 + +G(3df,3pd). Equilibrium geometries are produced within 0.0005 A of large-basis results for the latter two pairings. Though a single, iterative SCF response equation must be solved (unlike standard SCF gradients), it may be obtained in the smaller basis set, and integral screening further reduces the cost for well-chosen subsets. Total nuclear force calculations exhibit up to 75% savings, relative to large-basis calculations.


Period locking due to delayed feedback in a laser with saturable absorber.
We consider laser with saturable absorber operating in the pulsating regime that is subject to delayed feedback. Alone, both the saturable absorber and delayed feedback cause the clockwise output to become unstable to periodic output via Hopf bifurcations. The delay feedback causes the laser pulse period to lock to an integer fraction of the feedback time. We derive a map from the original model to describe the periodic pulsations of the laser. Equations for the period of the laser predict the occurrence of the different locking states as well as the value of the pump when there is a switch between the locked states.


Pro-Inflammatory Cytokine TNF-α Attenuates BMP9-Induced Osteo/ Odontoblastic Differentiation of the Stem Cells of Dental Apical Papilla (SCAPs).
Periapical periodontitis is a common oral disease caused by bacterial invasion of the tooth pulp, which usually leads to local release of pro-inflammatory cytokines and osteolytic lesion. This study is intended to examine the effect of TNF-α on BMP9-induced osteogenic differentiation of the stem cells of dental apical papilla (SCAPs). Rat model of periapical periodontitis was established. TNF-α expression was assessed. Osteogenic markers and ectopic bone formation in iSCAPs were analyzed upon BMP9 and TNF-α treatment. Periapical periodontitis was successfully established in rat immature permanent teeth with periapical lesions, in which TNF-α was shown to release during the inflammatory phase. BMP9-induced alkaline phosphatase activity, the expression of osteocalcin and osteopontin, and matrix mineralization in iSCAPs were inhibited by TNF-α in a dose-dependent fashion, although increased AdBMP9 partially overcame TNF-α inhibition. Furthermore, high concentration of TNF-α effectively inhibited BMP9-induced ectopic bone formation in vivo. TNF-α plays an important role in periapical bone defect during the inflammatory phase and inhibits BMP9-induced osteoblastic differentiation of iSCAPs, which can be partially reversed by high levels of BMP9. Therefore, BMP9 may be further explored as a potent osteogenic factor to improve osteo/odontogenic differentiation in tooth regeneration in chronic inflammation conditions.


Drug-drug Interaction between Losartan and Paclitaxel in Human Liver Microsomes with Different CYP2C8 Genotypes.
The cytochrome P450 (CYP) 2C8*3 allele is associated with reduced metabolic activity of paclitaxel. This study was aimed to investigate the inhibitory effect of losartan on paclitaxel metabolism in human liver microsomes (HLMs) and to determine the impact of the CYP2C8*3 polymorphism. HLMs that contained the CYP2C8*1 homozygote (HL60) or CYP2C8*3 heterozygote (HL54) genotype were used for the inhibition study. Losartan, at a concentration of 50 μmol/L, significantly inhibited paclitaxel metabolism by 29% and 57% in the HL60 (p < 0.001) and HL54 (p < 0.01), respectively. When using HL60, losartan and the CYP3A4-selective inhibitors, erythromycin and ketoconazole, caused a greater inhibition of the paclitaxel metabolism than quercetin, a CYP2C8-selective inhibitor. This demonstrated that the paclitaxel metabolism was mainly catalysed by CYP3A4 in HL60. There were no significant differences found for the inhibitory effects caused by the four inhibitors of the paclitaxel metabolism in HL54, indicating that both CYP2C8 and CYP3A4 play important roles in paclitaxel metabolism in HL54. These findings suggest that 50 μmol/L of losartan inhibits both CYP2C8 and CYP3A4 in HLMs. In summary, losartan inhibited paclitaxel metabolism, with concentrations over 50 μmol/L in HLMs. The CYP2C8*3 allele carriers are likely susceptible to the interactions of losartan and CYP3A4 inhibitors to paclitaxel metabolism.


Keratoplasty in Hungary.
The first keratoplasty was performed in Hungary in 1909, but the transplantations were started in large numbers after the Second World War in Debrecen. Since 1992 a National Keratoplasty Register is functioning at the Department of Ophthalmology Debrecen. The present paper gives an overview on the current status of keratoplasty in Hungary based on the data of this Register. The number of corneal transplantations more than doubled in the past two decades. In the past 3 years (2005 to 2008) the number of transplantation seemed to stabilize around a bit more than 700. The ratio of preserved corneas disclosed a constant increase. The turning point was 1997, few years after the establishment of the Debrecen Eye Bank in 1994, when more preserved corneas were transplanted than fresh ones. The law regulating the procurement and the transplantation of corneas in our country is based on presumed consent and explicit objection which is the better type of regulation for the performance of keratoplasties in large numbers. The number of corneal transplantations in Hungary in the past decades was similar to the figures of industrial countries.


Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols.
Epidemiological studies have revealed an increased risk of cancer, notably soft-tissue sarcomas and non-Hodgkin's lymphomas, in people occupationally exposed to chlorophenoxy herbicides, including those contaminated by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). We report here a historical cohort study of mortality in an international register of 18,910 production workers or sprayers from ten countries. Exposure was reconstructed through questionnaires, factory or spraying records, and job histories. Cause-specific national death rates were used as reference. No excess was observed in all-cause mortality, for all neoplasms, for the most common epithelial cancers, or for lymphomas. A statistically non-significant two-fold excess risk, based on 4 observed deaths, was noted for soft-tissue sarcoma with a standardised mortality ratio (SMR) of 196 and 95% confidence interval (Cl) 53-502; this was concentrated as a six-fold statistically significant excess, occurring 10-19 years from first exposure in the cohort as a whole (SMR = 606 [165-1552]) and, for the same time period, as a nine-fold excess among sprayers (SMR = 882 [182-2579]). Risks appeared to be increased for cancers of the testicle, thyroid, other endocrine glands, and nose and nasal cavity, based on small numbers of deaths. The excess of soft-tissue sarcomas among sprayers is compatible with a causal role of chlorophenoxy herbicides but the excess does not seem to be specifically associated with those herbicides probably contaminated by TCDD.


Communal peace in Bangladesh after Rohingya crisis: An assessment of different approaches to community development.
The recent persecution of Rohingyas, a Muslim ethnic minority group of Western Rakhine state, by state military has forced more than half a million people to take refuge in Bangladesh. It has sparked tension between Muslims and Buddhists in Bangladesh as different research and mass media reports illustrated the role of Buddhist nationalist groups in the massacre of Rohingyas. Thus, Bangladesh is vulnerable to communal violence not only based on religion but also based on ethnic, class, race, and national identity. This paper reviews existing community development theories to assess potential approaches' capability of ensuring communal peace in Bangladesh. The assessment includes the analysis of major community development theories and approaches and their applicability to a given context. The analysis argues that due to the scarcity of assets and resources community development approaches in a humanitarian crisis need some external intervention and bureaucratic supervision. Otherwise, it would be difficult to deploy any community development approach to ensure communal peace leading to sustainable development.


A JAK Inhibitor for Treatment of Rheumatoid Arthritis: The Baricitinib Experience.
Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved as monotherapy or in combination with methotrexate for treating adults with moderate-to-severe active rheumatoid arthritis (RA) and provides improvements in clinical signs, symptoms and patient-reported outcomes. Currently, baricitinib is approved for treating RA in more than 75 countries. In several pivotal Phase II and III RA trials (RA-BALANCE, RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BEYOND), up to seven years of baricitinib treatment was well tolerated and provided rapid and sustained efficacy, which was confirmed in real-world settings. Safety signals for another JAK inhibitor, tofacitinib, have emerged, as observed in the post-marketing Phase IIIb/IV trial Oral Rheumatoid Arthritis Trial (ORAL) Surveillance; safety signals were subsequently highlighted in a retrospective study of baricitinib and consequently new recommendations and warnings and precautions for all JAK inhibitors have been issued. Ongoing studies to further characterise and clarify the benefit:risk of JAK inhibitors include registries and controlled trials. This capstone review summarises clinical and real-world data outlining the benefit:risk profile of baricitinib, confirming that the improved disease activity and physical function of patients with RA treated with this JAK inhibitor observed in clinical trials is translated into effectiveness in clinical practice, with a low rate of discontinuations.


Horseback riding therapy for a deafblind individual enabled by a haptic interface.
We present a haptic interface to help deafblind people to practice horseback riding as a recreational and therapeutic activity. Horseback riding is a form of therapy which can improve self-esteem and sensation of independence. It has been shown to benefit people with various medical conditions-including autism. However, in the case of deafblind riders, an interpreter must stand by at all times to communicate with the rider by touch. We developed a simple interface that enables deafblind people to enjoy horseback riding while the instructor is remotely providing cues, which improves their independence. Experiments demonstrated that an autistic deafblind individual exhibits similar responses to navigational cues as an unimpaired rider. Motivation is an important factor in therapy, and is frequently determinant of its outcome; therefore, the user attitude toward the therapy methods is key. The answers to questionnaires filled by the rider, family, and the instructor show that our technique gives the rider a greater sense of independence and more joy compared to standard riding where the instructor is walking along with the horse.


A molecular genetic model of astrocytoma histopathology.
As the molecular events responsible for astrocytoma formation and progression are being clarified, it is becoming possible to correlate these alterations with the specific histopathological and biological features of astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. In WHO grade II astrocytomas, autocrine stimulation by the plateletderived growth factor system coupled with inactivation of the p53 gene may lead to a growth stimulus in the face of decreased cell death with slow net growth ensuing. Such cells would also have defective responses to DNA damage and impaired DNA repair, setting the stage for future malignant change. Such biological scenarios recapitulate many of the clinicopathological features of WHO grade II astrocytomas. Anaplastic astrocytomas further display release of a critical cell cycle brake that involves the CDKN2/p16, RB and CDK4 genes. This results in mitoses seen histologically; clinically, there is more conspicuous, rapid growth. Finally, glioblastomas may emerge from the microenvironmental outgrowth of more malignant clones in a complex vicious cycle that involves necrosis, hypoxia, growth factor release, angiogenesis and clonal selection; growth signals mediated by activation of epidermal growth factor receptors may precipitate glioblastomas. It is clear as well that glioblastoma multiforme can arise via a number of independent genetic pathways, although the clinical significance of these distinctions remains unclear.


Post-translational modification in microviridin biosynthesis.
Cyanobacteria are prolific producers of bioactive natural products that mostly belong to the nonribosomal peptide and polyketide classes. We show here how a linear precursor peptide of microviridin K, a new member of the microviridin class of peptidase inhibitors, is processed to become the mature tricyclic peptidase inhibitor. The microviridin (mvd) biosynthetic gene cluster of P. agardhii comprises six genes encoding microviridin K, an apparently unexpressed second microviridin, two RimK homologues, an acetyltransferase, and an ABC transporter. We have over-expressed three enzymes of this pathway and have demonstrated their biochemical function in vitro through chemical degradation and mass spectrometry. We show that a prepeptide undergoes post-translational modification through cross-linking by ester and amide bond formation by the RimK homologues MvdD and MvdC, respectively. In silico analysis of the mvd gene cluster suggests the potential for widespread occurrence of microviridin-like compounds in a broad range of bacteria.


4-(4-Nitro-benz-yl)morpholine.
In the title compound, C(11)H(14)N(2)O(3), an inter-molecular inter-action between a nitro group O atom and a neighboring benzene ring helps to stabilize the crystal structure [N⋯centroid = 3.933 (2) Å]. No classical hydrogen bonds are observed in the crystal packing.


Bromocriptine in augmentation of antipsychotic response in chronic schizophrenia: a negative pilot report.
To further assess the usefulness of bromocriptine in treatment of schizophrenia seven inpatient chronic schizophrenics with acute exacerbation who had failed to respond to four weeks of antipsychotic therapy were treated with bromocriptine 2.5 mg daily for a treatment duration varying from one dose to four weeks while their antipsychotic dose was continued unchanged. Mean age of patients was 38.9 +/- 11.6 years and mean number of prior psychiatric hospitalizations was 12.0 +/- 7.2. Patients were rated with the Brief Psychiatric Rating Scale prior to the first bromocriptine dose, at 24 hours after dosage initiation, and at weekly intervals. One patient showed clinically significant improvement in both positive and negative schizophrenic symptoms. One patient showed slight improvement in unusual thought content, and four patients were clinically unchanged. One patient significantly worsened after the first dose. Factors possibly contributing to response and non-response are discussed. This is a report of an open study in 7 patients. It is the only report of bromocriptine treatment in patients previously shown unresponsive to antipsychotics and whose antipsychotics dose was held constant throughout the study. Addition of bromocriptine to the antipsychotic regimen remains an unproven treatment approach which may be considered only in patients refractory to or inadequately controlled with antipsychotics.


Mesoporous MnCeOx solid solutions for low temperature and selective oxidation of hydrocarbons.
The development of noble-metal-free heterogeneous catalysts that can realize the aerobic oxidation of C-H bonds at low temperature is a profound challenge in the catalysis community. Here we report the synthesis of a mesoporous Mn0.5Ce0.5Ox solid solution that is highly active for the selective oxidation of hydrocarbons under mild conditions (100-120 °C). Notably, the catalytic performance achieved in the oxidation of cyclohexane to cyclohexanone/cyclohexanol (100 °C, conversion: 17.7%) is superior to those by the state-of-art commercial catalysts (140-160 °C, conversion: 3-5%). The high activity can be attributed to the formation of a Mn0.5Ce0.5Ox solid solution with an ultrahigh manganese doping concentration in the CeO2 cubic fluorite lattice, leading to maximum active surface oxygens for the activation of C-H bonds and highly reducible Mn(4+) ions for the rapid migration of oxygen vacancies from the bulk to the surface.


Short-term quality of life change perceived by patients after transition to mandibular overdentures
The aim of this longitudinal observational study was to evaluate the oral health-related quality of life (OHRQoL) following patient rehabilitation with implant-retained mandibular overdentures (IMO) and to identify the contribution of the different domains to OHRQoL. The Oral Health Impact Profile (OHIP-EDENT), Dental Impact on Daily Living (DIDL), and Geriatric Oral Health Assessment Index (GOHAI) questionnaires were completed twice by 25 patients: after 3 months of rehabilitation with complete dentures (CD) and after 3 months of IMO loading using stud abutments. The evaluation after IMO rehabilitation showed significant improvement in three DIDL domains: appearance (p = 0.011), eating and chewing (p = 0.003), and general performance (p = 0.003). The GOHAI results showed significant differences in two domains: psychosocial (p = 0.005) and pain and discomfort (p = 0.0004). The OHIP-EDENT outcomes showed significant improvements in five domains: functional limitation (p = 0.0001), physical pain (p = 0.0002), physical disability (p = 0.0010), and psychological disability and handicap (p = 0.032). The largest observed effect sizes were close to one standard deviation and were observed in the eating and chewing domain (0.93) of the DIDL; the pain and discomfort domain (0.83) of the GOHAI, and the functional limitation (0.89), physical pain (1.02), physical disability (0.84) domains of the OHIP-EDENT. The percentage of satisfied patients increased in all domains. Self-reported OHRQoL of CD wearers was significantly improved after 3 months of treatment with IMO, especially concerning the functional and pain-related aspects.


Ground squirrel hepatitis virus (GSHV) infection and hepatocellular carcinoma in the Canadian Richardson ground squirrel (Spermophilus richardsonii).
Sera and livers from 40 Richardson ground squirrels were examined for evidence of ground squirrel hepatitis virus (GSHV) infection and hepatocellular carcinoma. Twenty-five sera were obtained from fully grown adult ground squirrels and 15 from young ground squirrels estimated to be between 6-8 weeks of age. All animals had been caught in the wild and had spent less than 1 month in captivity. Sixteen sera (40%) had at least one serologic marker of GSHV (2 with GSHV surface antigen, 3 GSHV core antigen, 5 GSHV antibody to core antigen and 11 GSHV antibody to surface antigen). Two cases of hepatocellular carcinoma were detected, both in adult ground squirrels. Tumour tissue and adjacent normal liver tissue were negative for GSHV surface and core antigen by direct immunofluorescence in both livers and negative for GSHV-DNA by molecular hybridization in the one tumour examined. These results indicate that: A) GSHV is geographically more widespread than previously considered; B) viral transmission occurs early in life, probably via the vertical route; and C) hepatocellular carcinoma is a relatively common finding in these animals while still in their wild state. Any causal relationship between hepatocellular carcinoma and GSHV infection in these animals, however, has yet to be demonstrated.


Switchable dual-band to broadband terahertz metamaterial absorber incorporating a VO2 phase transition.
We design and demonstrate a thermally switchable terahertz metamaterial absorber consisting of an array of orthogonal coupled split-ring metal resonators involving a VO2 phase transition. Numerical results indicate that the active metamaterial always absorbs the TE wave in dual-band regardless of insulating and metallic VO2, while the insulator-to-metal phase transition enables a switchable effect between dual-band and broadband absorption of the TM wave with the resonant frequency tunability of 33%. Especially under the metallic VO2 state, the absorption properties are polarization-dependent and exhibit a switching effect between dual-band and broadband absorption with the increase of the polarization angle. The tunable absorption mechanism can be explained by effective impedance theory and electric energy density distributions. The proposed dual-band to broadband metamaterial switching absorber may have broad applications in sensors, imaging and emitters.


Analysis of precision in tumor tracking based on optical positioning system during radiotherapy.
Tumor tracking is performed during patient set-up and monitoring of respiratory motion in radiotherapy. In the clinical setting, there are several types of equipment for this set-up such as the Electronic Portal imaging Device (EPID) and Cone Beam CT (CBCT). Technically, an optical positioning system tracks the difference between the infra ball reflected from body and machine isocenter. Our objective is to compare the clinical positioning error of patient setup between Cone Beam CT (CBCT) with the Optical Positioning System (OPS), and to evaluate the traditional positioning systems and OPS based on our proposed approach of patient positioning. In our experiments, a phantom was used, and we measured its setup errors in three directions. Specifically, the deviations in the left-to-right (LR), anterior-to-posterior (AP) and inferior-to-superior (IS) directions were measured by vernier caliper on a graph paper using the Varian Linear accelerator. Then, we verified the accuracy of OPS based on this experimental study. In order to verify the accuracy of phantom experiment, 40 patients were selected in our radiotherapy experiment. To illustrate the precise of optical positioning system, we designed clinical trials using EPID. From our radiotherapy procedure, we can conclude that OPS has higher precise than conventional positioning methods, and is a comparatively fast and efficient positioning method with respect to the CBCT guidance system.


Correction of Large Oro-antral Communications From Previously Failed Implant Treatment: Reconstruction of Hard and Soft Tissues.
As dental implants become more popular for the treatment of partial and total edentulism and treatment of "terminal dentitions," techniques for the management of the atrophic posterior maxillae continue to evolve. Although dental implants carry a high success rate long term, attention must be given to the growing numbers of revisions or retreatment of cases that have had previous dental implant treatment and/or advanced bone replacement procedures that, due to either poor patient compliance, iatrogenic error, or poor quality of the pre-existing alveolar and/or soft tissues, have led to large osseous defects, possibly with deficient soft-tissue volume. In the posterior maxillae, where the poorest quality of bone in the oral cavity exists, achieving regeneration of the alveolar bone and adequate volume of soft tissue remains a complex procedure. This is made even more difficult when dealing with loss of dental implants previously placed, aggressive bone reduction required in various implant procedures, and/or residual sinus infections precluding proper closure of the oral wound margins. The purpose of this article is to outline a technique for the total closure of large oro-antral communications, with underlying osseous defects greater than 15 mm in width and 30 mm in length, for which multiple previous attempts at closure had failed, to achieve not only the reconstruction of adequate volume and quality of soft tissues in the area of the previous fistula, but also total regeneration of the osseous structures in the area of the large void.


The Charlotte Large artery occlusion Endovascular therapy Outcome Score predicts independent outcome after thrombectomy.
Predicting functional outcomes after endovascular thrombectomy (EVT) is of interest to patients and families as they navigate hospital and post-acute care decision-making. We evaluated the prognostic ability of several scales to predict good neurological function after EVT. We retrospectively analyzed records from a health system's code stroke registry, including consecutive successful thrombectomy patients from August 2020 to February 2023 presenting with an anterior circulation large vessel occlusion who were evaluated with pre-EVT CT perfusion. Primary and secondary outcomes were 90-day modified Rankin Scale (mRS) scores 0-2 and 0-1, respectively. Logistic regression was performed to evaluate the ability of each scale to predict the outcomes. Scales were compared by calculating the area under the curve (AUC). A total of 465 patients (mean age 68.1 [±14.9] years, median National Institutes of Health Stroke Scale [NIHSS] 16 [11-21]) met inclusion criteria. In the logistic regression, the Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS), Totaled Health Risks in Vascular Events, Houston Intra-Arterial Therapy-2, Pittsburgh Response to Endovascular therapy, and Stroke Prognostication using Age and NIHSS were significant in predicting the primary and secondary outcomes. CLEOS was superior to all other scales in predicting 90-day mRS 0-2 (AUC .75, 95% confidence interval [CI] .70-.80) and mRS 0-1 (AUC .74, 95% CI .69-.78). Twenty of 22 patients (90.9%) with CLEOS <315 had 90-day mRS 0-2. CLEOS predicts independent and excellent neurological function after anterior circulation EVT.


Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells.
NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose 6-phosphate dehydrogenase (G6PD), malic enzyme, and the cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc). Little information is available about the role of IDPc in antioxidant defense. In this study we investigated the role of IDPc against cytotoxicity induced by oxidative stress by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 3-4-fold higher and 35% lower, respectively, than that in the parental cells carrying the vector alone. Although the activities of other antioxidant enzymes, such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and G6PD, were comparable in all transformed cells, the ratio of GSSG to total glutathione was significantly higher in the cells expressing the lower level of IDPc. This finding indicates that IDPc is essential for the efficient glutathione recycling. Upon transient exposure to increasing concentrations of H(2)O(2) or menadione, an intracellular source of free radicals and reactive oxygen species, the cells with low levels of IDPc became more sensitive to oxidative damage by H(2)O(2) or menadione. Lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against oxidative stress, compared to the control cells. This study provides direct evidence correlating the activities of IDPc and the maintenance of the cellular redox state, suggesting that IDPc plays an important role in cellular defense against oxidative stress.


Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy.
Metformin is under evaluation as a potential anticancer agent. Expression of total and phospho(Thr172)-adenosine monophosphate-activated kinase-α (AMPKα and pAMPKα(Thr172) respectively), a main metformin target, was examined in radiotherapy treated breast cancers and metformin's ability to modulate Trx system expression and breast cancer radiosensitivity evaluated in vitro. AMPKα and pAMPKα(Thr172) expression was assessed using a discovery (n=166) and validation cohort (n=609). Metformin's role in regulating radioresponse, and Trx family expression, was examined via clonogenic assays and Western blots. Intracellular reactive oxygen species (ROS) levels, cell cycle progression and apoptosis were assessed by flow cytometry. High AMPKα expression associated with improved local recurrence-free (P=0.019), relapse-free (P=0.016) and breast cancer-specific survival (P=0.000065) and was, from multivariate analysis, an independent prognostic factor from the discovery cohort. From the validation cases AMPKα expression associated with relapse-free and breast cancer-specific survival in luminal breast cancers. Metformin substantially increased radiosensitivity, intracellular ROS levels and reduced Trx expression, in luminal breast cancer cells, but had little effect on basal phenotype cells. In conclusion, high AMPKα expression associates with improved prognosis, especially in luminal breast cancer. Metformin preferentially radiosensitises luminal breast cancer cells, potentially due to alterations to intracellular ROS levels via modulation of Trx family protein expression.


Dried blood spots sampling in case samples deprived of hematocrit level information - Investigation and calculation strategy.
The application of a new calculation strategy for the psychotropic drug concentration in blood and bone marrow samples in the form of dried blood spots (DBS) was the main aim of the study. The standard DBS method consists of the deposition of the capillary blood onto the dedicated paper cards. Nowadays, the DBS technique is seen as a fast and partly superior microsampling alternative methodology replacing the conventional venous blood and plasma collection. The calculation approach to drug concentration in the limited volume of the case sample, where the hematocrit level cannot be determined, constitutes an important step of this method. The method has been validated and the results of the determination of alprazolam and diazepam previously spiked in the post-mortem blood and bone marrow sample have been satisfactory.


Elevated serum PIIINP and laminin in inflammatory bowel disease indicate hepatobiliary and pancreatic dysfunction.
Levels of S-PIIINP (serum aminoterminal propeptide of type III procollagen) have been shown to be increased in patients with primary sclerosing cholangitis and inflammatory bowel disease. The aim of the study was to investigate the serum concentrations of PIIINP and laminin in inflammatory bowel disease patients, their relationship with inflammatory bowel disease-associated hepatobiliary and pancreatic dysfunction, and to correlate them with clinical, endoscopic, and histologic variables. S-PIIINP and S-laminin were measured in 222 consecutive inflammatory bowel disease patients, who were screened for abnormal liver and pancreatic enzymes and for pancreatic exocrine hypofunction with the p-aminobenzoic acid test (215 patients). The patients with abnormal screening results were further scheduled for endoscopic retrograde cholangiopancreatography, liver biopsy, secretin test and ultrasound. S-PIIINP and S-laminin were abnormally high in 19% and 40% of all inflammatory bowel disease patients, respectively. The elevated levels of the fibrosis markers were associated with laboratory signs of either hepatobiliary or pancreatic disease. Hepatobiliary disease was found in 37 (17%) of inflammatory bowel disease patients, 15 of whom had primary sclerosing cholangitis. The median levels of S-PIIINP and S-laminin were significantly higher in patients with hepatobiliary disease than in those without (P < 0.0001 and P < 0.001, respectively), being most strikingly elevated in primary sclerosing cholangitis. Abnormal pancreatic screening tests were found in 67 (30%) patients. High levels of S-PIIINP and S-laminin were also significantly associated with low values in p-aminobenzoic acid (P < 0.001 and P < 0.005) and secretin (P < 0.01 and P < 0.05) tests, but not with inflammatory bowel disease category, endoscopic or histological disease extent, frequency of bowel resection or actual clinical activity. In inflammatory bowel disease, increased S-PIIINP and S-laminin are associated with hepatobiliary and pancreatic disorders.


Modulating DNA Repair Pathways to Diversify Genomic Alterations in Saccharomyces cerevisiae.
Nuclease based genome editing systems have emerged as powerful tools to drive genomic alterations and enhance genome evolution via precise engineering in the various human and microbial cells. However, error-prone DNA repair has not been well studied previously to generate diverse genomic alterations and novel phenotypes. Here, we systematically investigated the potential interplay between DNA double strand break (DSB) repair and genome editing tools, and found that modulating the DSB end resection proteins could significantly improve mutational efficiency and diversity without exogenous DNA template in yeast. Deleting SAE2, EXO1, or FUN30, or overexpressing MRE11-H125N (nuclease-dead allele of MRE11), for DSB end resection markedly increased the efficiency of CRISPR/SpCas9 (more than 22-fold) and CRISPR/AsCpf1 (more than 30-fold)-induced mutagenesis. Deleting SAE2 or overexpressing MRE11-H125N substantially diversified CRISPR/SpCas9 or AsCpf1-induced mutation 2-3-fold at URA3 locus, and 3-5-fold at ADE2 locus. Thus, the error-prone DNA repair protein was employed to develop a novel mutagenic genome editing (mGE) strategy, which can increase the mutation numbers and effectively improve the ethanol/glycerol ratio of Saccharomyces cerevisiae through modulating the expression of FPS1 and GPD1. This study highlighted the feasibility of potentially reshaping the capability of genome editing by regulating the different DSB repair proteins and can thus expand the application of genome editing in diversifying gene expression and enhancing genome evolution. IMPORTANCE Most of the published papers about nuclease-assisted genome editing focused on precision engineering in human cells. However, the topic of inducing mutagenesis via error-prone repair has often been ignored in yeast. In this study, we reported that perturbing DNA repair, especially modifications of the various DSB end resection-related proteins, could greatly improve the mutational efficiency and diversity, and thus functionally reshape the capability of the different genome editing tools without requiring an exogenous DNA template in yeast. Specifically, mutagenic genome editing (mGE) was developed based on CRISPR/AsCpf1 and MRE11-H125N overexpression, and used to generate promoters of different strengths more efficiently. Thus, this work provides a novel method to diversify gene expression and enhance genome evolution.


STRUCTURE OF AN ASYMMETRIC HYBRID ZONE BETWEEN TWO WATER STRIDER SPECIES (HEMIPTERA: GERRIDAE: LIMNOPORUS).
The water stricter species Limnoporus dissortis and L. notabilis hybridize across a broad zone in western Canada. Body length and alleles at four allozyme loci show a steep cline along the east slope of the Rocky Mountains in western Alberta, while in central British Columbia the parental phenotypes coexist without merging fully. One sex-linked locus shows little introgression, while there is apparently considerable gene flow at three autosomal loci. Although the hybrid zone has characteristics of a broad tension zone, the spatial distribution of introgression suggests that habitat patchiness and differential habitat associations of the two species also contribute to the pattern of hybridization. Asymmetry in interspecific mating success and incompatibilities of sex chromosomes with each other or with cytoplasmic factors appear to account for the occurrence of L. dissortis genotypes within the range of L. notabilis, and the lack of L. notabilis genotypes within the range of L. dissortis. The genetic structure of this hybrid zone supports the importance of sex-linked traits in maintaining the integrity of species, while its spatial structure suggests that extrinsic habitat features can combine with intrinsic genetic incompatibilities to produce complex hybrid interactions.


Platelet Factor 4 Interactions with Short Heparin Oligomers: Implications for Folding and Assembly.
Association of platelet factor 4 (PF4) with heparin is a first step in formation of aggregates implicated in the development of heparin-induced thrombocytopenia (HIT), a potentially fatal immune disorder affecting 1-5% of patients receiving heparin. Despite being a critically important element in HIT etiology, relatively little is known about the specific molecular mechanism of PF4-heparin interactions. This work uses native mass spectrometry to investigate PF4 interactions with relatively short heparin chains (up to decasaccharides). The protein is shown to be remarkably unstable at physiological ionic strength in the absence of polyanions; only monomeric species are observed, and the extent of multiple charging of corresponding ions indicates a partial loss of conformational integrity. The tetramer signal remains at or below the detection threshold in the mass spectra until the solution's ionic strength is elevated well above the physiological level, highlighting the destabilizing role played by electrostatic interactions vis-à-vis quaternary structure of this high-pI protein. The tetramer assembly is dramatically facilitated by relatively short polyanions (synthetic heparin-mimetic pentasaccharide), with the majority of the protein molecules existing in the tetrameric state even at physiological ionic strength. Each tetramer accommodates up to six pentasaccharides, with at least three such ligands required to guarantee the higher-order structure integrity. Similar results are obtained for PF4 association with longer and structurally heterogeneous heparin oligomers (decamers). These longer polyanions can also induce PF4 dimer assembly when bound to the protein in relatively low numbers, lending support to a model of PF4/heparin interaction in which the latter wraps around the protein, making contacts with multiple subunits. Taken together, these results provide a more nuanced picture of PF4-glycosaminoglycan interactions leading to complex formation. This work also advocates for a greater utilization of native mass spectrometry in elucidating molecular mechanisms underlying HIT, as well as other physiological processes driven by electrostatic interactions.


Function of children with myelodysplasia and lower extremity amputations.
This is a retrospective study of the functional status of children who underwent a lower extremity amputation for complications of myelodysplasia. With a computerized surgical database, 12 children with myelodysplasia who underwent an amputation at the Boyd level or above at a single children's referral hospital between 1983 and 2001 were identified. Four patients could not be contacted, but the remaining 8 patients were evaluated through chart review and interview to assess the impact of the amputation on their function. With a mean follow-up time of 9 years (range, 5-15 years), all 6 of the patients with a below-knee or Boyd amputation continued to ambulate using a prosthesis. Most patients occasionally reported having ulcers on their residual limb, but these cases were easily managed and did not result in amputation revisions.The only patient in this series with an above-knee amputation and the only patient with a knee disarticulation were exclusively wheelchair ambulators and no longer owned a prosthesis. This study supports the notion that children with myelodysplasia can have amputations and successfully wear a prosthesis to maintain their ambulation.


Modulation by recombinant DNA leukocyte (alpha) and fibroblast (beta) interferons of the expression and shedding of HLA- and tumor-associated antigens by human melanoma cells.
With a panel of monoclonal antibodies, the effect of recombinant human leukocyte interferons (i.e., IFN-alpha A, IFN-alpha D), of a hybrid leukocyte IFN (i.e., IFN-alpha A/D (Bg1)), and of recombinant fibroblast (beta) IFN on the expression and shedding of four types of melanoma-associated antigens (MAA) and of HLA antigens by the cultured melanoma cell line Colo 38 was investigated. None of the IFN affected the expression of the high m.w. melanoma-associated antigen (HMW-MAA), but all of them increased its shedding. The expression and shedding of the 115,000 MAA and of the 100,000 MAA were increased by IFN; the magnitude of the effect as well as the kinetics were different for the various IFN preparations. The cytoplasmic MAA was the most sensitive to modulation by IFN, because all four types increased its surface expression, its total content, and its shedding. The three types of leukocyte IFN, as well as the fibroblast IFN, were all effective in increasing the expression of HLA-A,B,C antigens, the effect being more marked on the free heavy chain than on the HLA-A,B,C complex. However, only leukocyte IFN enhanced the shedding of the HLA-A,B,C molecular complex. The three types of leukocyte IFN and especially fibroblast IFN enhanced the expression of the gene products of the HLA-D region, the effect being more marked on DC-1 antigens than on HLA-DR antigens. No effect on the shedding of HLA-DR and DC-1 antigens was detected.


Genetic and environmental contributions to serum ascorbic acid concentrations: the Stanislas Family Study.
Although numerous environmental factors are documented to influence serum ascorbic concentrations, little is known about the genetic versus environmental contributions to variation of this trait. The aim of this study was to estimate family correlation and, additive genetic heritability and household effects in a variance component analysis for serum ascorbic acid concentrations. In a sample of ninety French families, information was obtained regarding serum ascorbic acid concentrations, usual dietary intake, lifestyle, and other related covariates. Spouse, parent-offspring and offspring-offspring significant correlation coefficients for serum ascorbic acid concentrations, adjusted for age, cigarette consumption and oral contraceptive use, were 0.432, 0.298 and 0.485, respectively, and for adjusted values for additional diet covariates (vitamin C intake and fruit and vegetable consumption), were 0.362, 0.154 and 0.348, respectively. Variance component analysis for serum ascorbic concentrations showed no significant genetic contribution to variability of this trait. Conversely, household common environment accounted for 27.7 and 42.6% in parents and offspring, respectively, after adjustment for age, cigarette consumption and oral contraceptive use. After adjustment for the two additional diet covariates (vitamin C intake and fruit and vegetable consumption) household common variance decreased to 13.6 and 30.5% in parents and offspring, respectively. These results show that serum ascorbic acid concentrations aggregate within healthy families partly due to diet intake but without a significant genetic component.


Comparison of the protective antigen variabilities of prevalent Newcastle disease viruses in response to homologous/heterologous genotype vaccines.
The genotype VII Newcastle disease virus (NDV) vaccine has begun to replace the traditional genotype II NDV vaccine and is widely used in the commercial poultry of China. However, the effect of homologous and heterogeneous anti-NDV serum on the evolution of prevalent NDV is unknown. To understand the effect of genotype II and VII anti-NDV serum on the evolution of genotype VII NDV strains, ZJ1 (waterfowl origin) and CH/SD/2008/128 (ND128; chicken origin) were used for serial passage of 30 generations in DF-1 cells without anti-NDV serum or with genotype II and VII anti-NDV serum independently. The F and HN genes of the 2 viruses were amplified for the 10th, 20th, and 30th generations of each serial passage group and compared with their respective original viruses. We found that there was only one mutation at position 248 in the F gene of ZJ1 due to the serum pressure of genotype VII anti-NDV. Similarly, mutations at residue 527 of the F gene, and position 9 and 319 of the HN gene of ND128 were noted in both anti-NDV serum groups. The results show that the nonsynonymous (NS)-to-synonymous (S) ratio of the F gene of ZJ1 virus was 1.6, and for the HN gene, it was 2.5 in the anti-II serum group. In the anti-VII serum group, the NS/S ratio for the F gene was 2.1, and for the HN gene, it was 2.5. The NS/S ratio of the F gene of the ND128 virus was 0.8, and for the HN gene, it was 3 in the anti-II serum group. Furthermore, the NS/S ratio of the F gene was 0.8, and the HN gene was 2.3 in the anti-VII group. Taken together, our findings highlight that there was no significant difference in the variation of protective antigens in genotype VII NDV under the selection pressure of homologous and heterogeneous genotype NDV inactivated vaccines.


Three-dimensional surface reconstruction and panoramic optical mapping of large hearts.
Optical mapping of electrical activity from the surface of the heart is a powerful tool for studying complex arrhythmias. However, a limitation of traditional optical mapping is that the mapped region is restricted to the field of view of the sensor, which makes it difficult to track electrical waves as they drift in and out of view. To address this, we developed an optical system that panoramically maps epicardial electrical activity in three dimensions. The system was engineered to accomodate hearts comparable in size to human hearts. It is comprised of a surface scanner that measures epicardial geometry and a panoramic fluorescence imaging system that records electrical activity. Custom software texture maps the electrical data onto a reconstructed epicardial surface. The result is a high resolution, spatially contiguous, mapping dataset. In addition, the three-dimensional positions of the recording sites are known, making it possible to accurately measure parameters that require geometric information, such as propagation velocity. In this paper, we describe the system and demonstrate it by mapping a swine heart.


The association of lower extremity peripheral vascular disease in patients undergoing coronary bypass surgery.
The association of lower extremity peripheral vascular disease (PVD) in patients undergoing coronary artery bypass (CAB) has been studied in two groups of patients who have been operated upon between January and May 1987. Group 1 consists of 125 cases in which only resting ankle-arm pressure index (AAPI) were evaluated. Group 2 consists of 50 cases where both resting and after exercise AAPI were recorded. In total, 17 cases of one extremity and in 10 both lower extremity resting AAPI were below 0.9 (15.4%). In Group 2 comparison of resting and after exercise AAPI on both sides showed no statistically significant difference. However in Group 2, 13 cases (26%) had after exercise AAPI below 0.9 and in 26 (52%) cases after exercise AAPI were lower than the resting AAPI. This study showed that, although the coexistence of PVD in patients undergoing CAB is not as high as the coexistence of CAD in patients undergoing peripheral vascular procedures, this percentage can increase when the presence of PVD is evaluated with an exercise test whenever possible.


Endoscopy-based management decreases the risk of postoperative recurrences in Crohn's disease.
To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence. From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn's disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. From 205 patients who underwent surgery, 161 patients (follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence (HR = 0.30, 95%CI: 0.13-0.70, P = 0.006). Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.


Allergenic activity of a major grass pollen allergen is elevated in the presence of nasal secretion.
Phl p5 is a major allergen of timothy grass and causes rhinitis and bronchial asthma in nearly all patients allergic to grass pollen. The biochemical processing of this molecule by the nasal mucosa at its first encounter and possible changes of its biologic activity are unknown. Two isoforms of the allergen were expressed in Escherichia coli and subsequently purified. Conversion of these preparations to various forms with molecular size between 10 and 20 kD in the presence of nasal secretion was observed. Surprisingly, in skin prick test assays with allergic patients the mixture of converted peptides caused significantly higher allergic response when compared with the parent protein. Allergenic activity of the recombinant N-terminal Phl p5a and the C-terminal Phl p5b as measured by skin prick test and histamine release assays was significantly higher than that of the respective parent molecules. Using pancreatic rather than nasal secretion, Phl p5b was completely degraded and its allergenicity was almost completely reduced. Proteolytic degradation converts Phl p5 to defined fragments with increased allergenicity. Complete degradation of Phl p5 on the mucosa could be a preventive strategy to destroy its potency for the induction of an allergic response.


[Effects of different acupuncture manipulation on plasma estradiol, testosterone and cortisol in patients with kidney deficiency].
Observation was made on the effect of different acupuncture manipulation on plasma estradiol (E2), testosterone (T), E2/T and cortisol (C) in 78 patients with kidney deficiency. The results showed that the level of E2 and T in women was lowered by both reinforcing manipulation (RFM) and reducing manipulation (RDM). E2/T index was lowered by RDM but not by RFM, and there was significance (P < 0.05) between the RDM group and RDM group in E2/T, but no significance between the man's groups. The level of C was decreased by RDM but not by RFM. The results suggest that the different manipulation effects are different on the level of sex hormones in women and the C content in patients with kidney deficiency.


Spectroscopic Studies of the Chan-Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity.
We report an investigation of the Chan-Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of competing oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) → Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan-Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.