[Comparison of Laccase Activity of Different Strains of Ganoderma spp.].
To explore the relationship between the laccase activity and growth of Ganoderma spp.,to screen the highproducing laccase strains. The mycelium was cultured in PDA solid medium,and the laccase activity was measured by ABTS+method. The content of polysaccharide was determined by phenol sulfuric acid method. Ganoderma gibbosum grew more rapidly in the early stage,and the laccase activity reached maximum( 1 476. 64 U/g) in the 4th day,which was 11. 37 times larger than that of sweet Ganoderma lucidum. Ganoderma gibbosum had the significant advantage after a comprehensive analysis. The polysaccharide content of Ganoderma lucidum of Shinshu was lower; the growth rate of Ganoderma lucidum strain S3 was stable, and the content of polysaccharide was medium. There are some differences in the growth rate of Ganoderma spp., and there is a certain correlation between the laccase activity and growth. Ganoderma gibbosum is the highest-producing laccase strain among the screening strains.


A critical review of the "enculturation hypothesis": the effects of human rearing on great ape social cognition.
Numerous investigators have argued that early ontogenetic immersion in sociocultural environments facilitates cognitive developmental change in human-reared great apes more characteristic of Homo sapiens than of their own species. Such revamping of core, species-typical psychological systems might be manifest, according to this argument, in the emergence of mental representational competencies, a set of social cognitive skills theoretically consigned to humans alone. Human-reared great apes' capacity to engage in "true imitation," in which both the means and ends of demonstrated actions are reproduced with fairly high rates of fidelity, and laboratory great apes' failure to do so, has frequently been interpreted as reflecting an emergent understanding of intentionality in the former. Although this epigenetic model of the effects of enculturation on social cognitive systems may be well-founded and theoretically justified in the biological literature, alternative models stressing behavioral as opposed to representational change have been largely overlooked. Here I review some of the controversy surrounding enculturation in great apes, and present an alternative nonmentalistic version of the enculturation hypothesis that can also account for enhanced imitative performance on object-oriented problem-solving tasks in human-reared animals.


Inhibition of DNA synthesis and IL-2 bioactivity in MLR by splenic pregnancy-associated natural suppressor cells involves the production of a TGF-beta 1-like molecule and a second distinct inhibitory factor.
Natural suppressor cells exhibiting a double-negative, immature T cell phenotype have been identified in maternal spleen during syngeneic murine pregnancy. In the present study, splenic pregnancy-associated natural suppressor (SPANS) cells are shown to express alpha/beta T cell receptors. SPANS cell-mediated inhibition of DNA synthesis by spleen cells responding in mixed lymphocyte reactions (MLR) is associated with a reduction in interleukin (IL)-2 bioactivity beginning after 96 h of culture. Although culture supernatants from suppressed MLR exhibit diminished ability to support the growth of IL-2-dependent CTLL-2 cells, SPANS cells themselves are unable to inhibit IL-2-driven CTLL-2 proliferation, suggesting that SPANS cells down-regulate IL-2 synthesis in MLR. IL-2 utilization in MLR is also inhibited by SPANS cells, since the addition of exogenous IL-2 fails to relieve the inhibitory effect of SPANS cells on lymphoproliferative responses in MLR. Flow cytofluorometric analysis reveals that MLR performed in the presence of SPANS cells contain normal percentages of CD4 and IL-2 receptor-bearing spleen cells. Thus, SPANS cells do not inhibit cellular proliferation in MLR by selectively interfering with clonal expansion of IL-2-producing helper T cells or by down-regulating IL-2 receptor expression. We have determined that SPANS cells inhibit DNA synthesis in MLR via the production of a transforming growth factor (TGF)-beta 1-like suppressor factor, since cellular proliferation in MLR is restored to normal levels in the presence of anti-TGF-beta 1 neutralizing antibody. However, IL-2 bioactivity in these cultures remains low in comparison to control MLR, suggesting the presence of a second distinct suppressor factor. Although the identity of this second inhibitory molecule has yet to be determined, neutralizing antibody studies have ruled out IL-10.


Perioperative Atrial Fibrillation in Noncardiac Surgeries for Malignancies and One-Year Recurrence.
Perioperative atrial fibrillation (POAF) in noncardiac surgeries is common. However, it is unclear whether such atrial fibrillation (AF) recurs in the long term. This study was a prospective, single-center, observational study that included patients who underwent noncardiac surgeries for malignancies. Patients were followed up for 1 year to evaluate the incidence of AF, ischemic stroke, and mortality. An event-triggered recorder was used in patients with POAF. The incidences were compared according to the presence of POAF. Of 752 consecutive patients, 77 (10.2%) developed POAF and wore an event recorder for 19 (12-30) days. AF and ischemic stroke at 1 year were observed in 24 patients (31.1%) and 2 patients (2.6%) with POAF and 4 patients (0.6%) and 3 patients (0.4%) without POAF, respectively. Of the 24 patients with POAF and AF recurrence, 22 (92%) were asymptomatic. Anticoagulation was prescribed in 67 patients (87%) with POAF. Multivariate Cox regression analysis demonstrated that a higher AF recurrence rate in patients with POAF was associated with hypertension (hazard ratio, 2.79; 95% confidence interval, 1.06-7.38) and serum creatinine level (hazard ratio for 20 μmol/L increase, 2.32; 95% confidence interval, 1.16-4.62). AF recurs in approximately 30% of patients with POAF with malignancy in the subsequent year; most recurrences are asymptomatic.


Myocarditis in Adult-Onset Still's Disease: Case-Based Review.
Cardiac involvement in adult-onset Still's disease (AOSD) usually manifests as a pericardial disease. Myocarditis is uncommon (prevalence of 7%). However, the cardiocirculatory failure is the second cause of life-threatening AOSD. Herein, we report the case of a 38-year-old man who was diagnosed with myocarditis caused by AOSD. He was treated medically with steroids and methotrexate, and his course was favorable. A literature search in PubMed/MEDLINE and Scopus databases from 1971 to 2019 identified 47 additional cases of myocarditis and AOSD. The main features found in these reports were reviewed and are the following: (i) myocarditis is a rare complication of AOSD manifested by fever, chest pain, dyspnea, and tachycardia; (ii) cardiac biomarkers, electrocardiogram (ECG), transthroracic echocardiography (ECHO), and cardiac magnetic resonance imaging (MRI) are useful noninvasive diagnostic tools; and (iii) myocarditis is a potentially life-threatening complication of AOSD but responds positively to steroids and other immunomodulatory drugs. This review suggests that this entity should be suspected in cases of acute febrile myocarditis after ruling out other causes since a prompt treatment results in a good prognosis.


Effects of Qi-therapy (external Qigong) on cardiac autonomic tone: a randomized placebo controlled study.
Heart-rate variability (HRV) was compared in 40 subjects receiving external Qi-therapy (QT) or placebo control therapy, in a randomized placebo controlled design experiment. There were significant time, and group x time interactions in heart rate (HR), low frequency (LF), high frequency (HF), and LF/HF. These suggest that QT reduced the HR and increased HRV as indicated by a reduced LF/HF power ratio of HRV. These findings suggest that QT stabilizes the sympathovagal function more than placebo therapy.


A novel lable-free electrochemical immunosensor for carcinoembryonic antigen based on gold nanoparticles-thionine-reduced graphene oxide nanocomposite film modified glassy carbon electrode.
In this paper, gold nanoparticle-thionine-reduced graphene oxide (GNP-THi-GR) nanocomposites were prepared to design a label-free immunosensor for the sensitive detection of carcinoembryonic antigen (CEA). The nanocomposites with good biocompatibility, excellent redox electrochemical activity and large surface area were coated onto the glassy carbon electrode (GCE) surface and then CEA antibody (anti-CEA) was immobilized on the electrode to construct the immunosensor. The morphologies and electrochemistry of the formed nanocomposites were investigated by using scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrometry, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). CV and differential pulse voltammetry (DPV) studies demonstrated that the formation of antibody-antigen complexes decreased the peak current of THi in the GNP-THi-GR nanocomposites. The decreased currents were proportional to the CEA concentration in the range of 10-500 pg/mL with a detection limit of 4 pg/mL. The proposed method was simple, fast and inexpensive for the determination of CEA at very low levels.


Protein microarrays identify disease-specific anti-cytokine autoantibody profiles in the landscape of immunodeficiency.
Anti-cytokine autoantibodies (ACAAs) are pathogenic in a handful of rare immunodeficiencies. However, the prevalence and significance of other ACAAs across immunodeficiencies have not yet been described. We profiled ACAAs in a diverse cohort of serum samples from patients with immunodeficiency and assessed the sensitivity and specificity of protein microarrays for ACAA identification and discovery. Highly multiplexed protein microarrays were designed and fabricated. Blinded serum samples from a cohort of 58 immunodeficiency patients and healthy control subjects were used to probe microarrays. Unsupervised hierarchical clustering was used to identify clusters of reactivity, and after unblinding, significance analysis of microarrays was used to identify disease-specific autoantibodies. A bead-based assay was used to validate protein microarray results. Blocking activity of serum containing ACAAs was measured in vitro. Protein microarrays were highly sensitive and specific for the detection of ACAAs in patients with autoimmune polyendocrine syndrome type I and pulmonary alveolar proteinosis, detecting ACAA levels consistent with those reported in the published literature. Protein microarray results were validated by using an independent bead-based assay. To confirm the functional significance of these ACAAs, we tested and confirmed the blocking activity of select ACAAs in vitro. Protein microarrays are a powerful tool for ACAA detection and discovery, and they hold promise as a diagnostic for the evaluation and monitoring of clinical immunodeficiency.


Chromosome banding studies in the Bateleur (Terathopius ecaudatus, Aves, Accipitridae).
The karyotype of the Bateleur (Terathopius ecaudatus) was studied with conventional and Ag-NOR staining, and using GTG and CBG banding. The karyotype organization is typically accipitrid, with satellites and few microchromosomes, close to the karyotypes of true vultures.


Effectiveness of Work, Activities of Daily Living, Education, and Sleep Interventions for People With Autism Spectrum Disorder: A Systematic Review.
To examine interventions addressing work, activities of daily living (ADLs), instrumental activities of daily living (IADLs), education, and sleep for people with autism spectrum disorder. A total of 23 studies were identified, and 9 work-, 11 ADL/IADL-, and 3 education-related interventions were examined. No sleep studies were identified. Use of mobile and tablet technologies for vocational skills was supported. Support for ADL/IADL intervention is variable, with indications that Cognitive Orientation to Occupational Performance, sensory integration, and contextual interventions may increase occupational performance. Preliminary evidence suggests that daily yoga and brief exercise may improve classroom performance and behavior; group physical activities may assist with school readiness variables. Evidence for using technologies for IADLs was limited, as was evidence determining effective interventions for feeding and eating issues. Studies investigating interventions related to sleep are lacking. More studies are needed in all areas, presenting opportunities for the expansion of science-driven occupational therapy practice and research for people with ASD.


Bioresorbable vascular scaffold for very late stent thrombosis resulting from ruptured neoatherosclerosis.
Very late stent thrombosis is a rare but devastating complication after percutaneous coronary revascularization. Pathological studies have demonstrated that neoatherosclerosis plays a major role in certain patients with very late stent thrombosis. Optical coherence tomography is able to unravel the underlying pathophysiology and may be used to select the best treatment option. This case report describes the use of a bioresorbable vascular scaffold (BVS) in a patient suffering from very late stent thrombosis due to a complicated plaque in the setting of intrastent neoatherosclerosis. To our knowledge, this therapeutic strategy has not been previously reported in patients suffering from very late stent thrombosis. In this scenario, BVS implantation might represent an attractive strategy in selected patients.


Facile electrochemical determination of tetrabromobisphenol A based on modified glassy carbon electrode.
In this study, surface-functionalized nitrogen-doped graphene was prepared with 1, 3, 6, 8-pyrenetetrasulfonic acid tetrasodium salt in a simple way. The characteristics of the material were demonstrated by UV-vis absorption spectra, X-ray photoelectron spectroscopy, and electrochemical experiments. Then, the glassy carbon electrode was modified by the functionalized nitrogen-doped graphene and hexadecyltrimethylammonium bromide for tetrabromobisphenol A (TBBPA) determination. The oxidation current response of TBBPA was enhanced at the modified electrode and the mechanism was investigated. Upon the optimization of assay parameters, including pH value, accumulation potential and time, the oxidation current was linearly related to the concentration of TBBPA in the range of 0.01-1μM with a detection limit of 9nM. Moreover, the modified electrode was applied to detect TBBPA in water samples with simple, low cost, and high efficiency.


Phenotypic Characterization and Transformation Attempts Reveal Peculiar Traits of Xylella fastidiosa Subspecies pauca Strain De Donno.
Xylella fastidiosa subsp. pauca strain De Donno has been recently identified as the causal agent of a severe disease affecting olive trees in a wide area of the Apulia Region (Italy). While insights on the genetics and epidemiology of this virulent strain have been gained, its phenotypic and biological traits remained to be explored. We investigated in vitro behavior of the strain and compare its relevant biological features (growth rate, biofilm formation, cell-cell aggregation, and twitching motility) with those of the type strain Temecula1. The experiments clearly showed that the strain De Donno did not show fringe on the agar plates, produced larger amounts of biofilm and had a more aggregative behavior than the strain Temecula1. Repeated attempts to transform, by natural competence, the strain De Donno failed to produce a GFP-expressing and a knockout mutant for the rpfF gene. Computational prediction allowed us to identify potentially deleterious sequence variations most likely affecting the natural competence and the lack of fringe formation. GFP and rpfF- mutants were successfully obtained by co-electroporation in the presence of an inhibitor of the type I restriction-modification system. The availability of De Donno mutant strains will open for new explorations of its interactions with hosts and insect vectors.


Significant effects of Z-Gln-Val-Val-OME, common sequences of thiol proteinase inhibitors on thiol proteinases.
The first studies on a series of the small synthetic thiol proteinase inhibitors, conservative common sequences in several thiol proteinase inhibitors, are described. Among the many interesting findings with synthetic thiol proteinase inhibitors was the observation that the most effective analogue, Z-Gln-Val-Val-Ala-Gly-OMe, whose amino and carboxyl groups were protected with Z and OMe, respectively, showed inhibitory activity on papain and cathepsin B and protected papain from egg cystatin, human low-molecular-weight kininogen and T-kininogen-induced inhibition but not from leupeptin-induced inhibition. Moreover, it was revealed that Z-Gln-Val-Val-OMe was the smallest peptide to exhibit a protective effect on papain.


Early adjustments in mitochondrial structure and function in skeletal muscle to high altitude: design and rationale of the first study from the Kilimanjaro Biobank.
The physiological acclimatisation and adaptation processes in skeletal muscle at high altitude are of high medical and social relevance not only to understand limitations in physical performance at high altitude but also to understand the consequences of hypoxemia and tissue hypoxia in critically ill patients. Of particular importance in these processes are the alterations in content and function of mitochondria and myoglobin. The majority of studies on oxygen delivery to the tissues and utilisation by the cellular metabolism at high altitude were performed after prolonged stay at high altitude and in altitude-adapted highlanders. However, these studies do not provide insight in the sequence of events during the physiological acclimatisation and adaptation processes. Therefore, it is important to identify the early alterations in structure and function of the major determinants of the oxygen transport via myoglobin and oxygen utilisation by the mitochondria in skeletal muscle at high altitude. To achieve this goal, it is of interest to collect, analyse and compare quadriceps muscle biopsies and venous blood samples of climbers, guides and porters before and after climbing Mount Kilimanjaro and in participants of the Kilimanjaro Marathon before and after the run. The samples will be carefully documented and stored in the Kilimanjaro Biobank and will be made available to other research groups.


Three types of atrioventricular reciprocating tachycardia using bilateral accessory pathways in a patient with Wolff-Parkinson-White syndrome.
Electrophysiologic studies were performed on a patient with Wolff-Parkinson-White syndrome and recurrent supraventricular tachycardia. Bilateral accessory pathways capable of antegrade and retrograde conduction and three different types of atrioventricular (AV) reciprocating tachycardia were demonstrated. One type of narrow QRS tachycardia used the normal AV pathway for antegrade conduction and the left-sided accessory pathway for retrograde conduction. Two types of wide QRS tachycardia (one with right bundle branch block and one with left bundle branch block) used both accessory pathways for antegrade and retrograde conduction, respectively, and were independent of the normal AV pathway. The data showed that bilateral accessory pathways have different electrophysiologic properties and participate in three different types of AV reciprocating tachycardia.


Comparative risks of all-cause mortality for Veterans with schizophrenia with ongoing receipt of clozapine and other antipsychotic medications.
To guide care for patients with schizophrenia, the Veterans Health Administration (VHA) evaluated the associations between current or recent use of clozapine and all-cause mortality and explored associations for other antipsychotic medications. Using a case-control design, patients with schizophrenia who died in fiscal years 2014-2018 were matched on age, sex, race, and VHA facility to up to 10 controls who were alive on the case's date of death (index date). Medication coverage during the 91 days before the index date was classified as none, partial (1-44 days), and consistent (45-91 days). Medication coverage patterns during the index period were compared to coverage patterns during the period of 92-182 days prior to index date with each medication coverage classified as no change, no coverage, increased, or decreased. Conditional logistic regression analyses controlling for patient characteristics identified no associations of consistent or increasing clozapine coverage with mortality; partial and decreasing coverage were associated with greater mortality and these effects did not differ from those of other the medications considered. Exploratory analyses considering non-clozapine antipsychotic agents suggest that consistent coverage by olanzapine may be associated with increased mortality, that mortality associated with olanzapine may be greater than aripiprazole, and that this effect can be attributed primarily to patients with diabetes. Further study of this topic is needed.


Donor-Acceptor Dissociation Energies of Group 13-15 Donor-Acceptor Complexes Containing Fluorinated Substituents: Approximate Lewis Acidities of (F3C)3M vs (F5C6)3M and the Effects of Phosphine Steric Bulk.
To study donor-acceptor complexes containing fluoroalkyl and -aryl substituents on the acceptors, ONIOM methods for optimizing large complexes and determining single point energies were tested. A two-layer ONIOM optimization procedure utilizing the MPW1K model followed by single point calculations using the composite three-layer ONIOM G2R3 method proved acceptable. The optimization model predicts M-X bond distances well when compared to experiment and shows that the distances increase discontinuously with the bulk of the phosphine. Unexpectedly, (RF)3B-XR3 and (RF)3Al-XR3 bond dissociation energies (ΔEDA) are comparable for several R substituents. For RF = CF3, both are predicted to exhibit M-X ΔEDA values in the range 55-80 kcal mol(-1), exceptionally strong for dative bond energies. For RF = C6F5, the ΔEDA values are predicted to lie in the range 30-45 kcal mol(-1). (F5C6)3BP(t-Bu)3, which does not contain a B-P bond, is predicted to display ΔEDA = 19 kcal mol(-1). The ΔEDA energies do not change smoothly as the steric bulk of the phosphine increases. However, intrinsic ΔEDA energies ΔEint show a regular increase as the donor ability of the phosphine increases, confirming that the reorganization energy of the individual moieties contributes sizably to the overall ΔEDA. The data indicate that PPh3 is approximately equivalent to PMe3 as a donor in terms of ΔEint.


An examination of the path between recent sexual violence and sexually transmitted infections.
Sexually transmitted infections (STIs) are among the most common infections in the United States and are particularly prevalent in survivors of sexual violence. The purpose of this study is to examine co-occurring risk factors for sexual violence and STIs including mental health, alcohol use, drug use, and multiple partners as intersecting pathways to STIs for women who experienced sexual abuse in the past year. Secondary analyses were conducted on cross-sectional data from women originally recruited as respondents for an epidemiologic survey funded by the Centers for Disease Control and Prevention (CDC): Project CHOICES. The survey was administered to 2,672 women in six settings: A large, urban jail and residential alcohol and drug treatment facilities (Texas); a gynecology clinic (Virginia); two primary care clinics (Virginia and Florida); and media solicitation (Florida). Women were included in the current study if they were fertile, sexually active, and not pregnant or trying to get pregnant (n = 1,183). Structural equation modeling (SEM) was used to test the conceptual path model between sexual violence and STI occurrence. In the SEM, there were no significant paths from mental health, alcohol severity, or drug use to STI occurrence contrary to the results of the initial bivariate analyses. Multiple sexual partners significantly mediated the relationship between sexual violence and STIs and between mental health and drug use and STIs. This study highlights the importance of providing effective treatment to survivors of sexual violence, which includes addressing risky sexual behaviors to reduce STI occurrence.


The retinohypothalamic tract in the cat: retinal ganglion cell morphology and pattern of projection.
The pattern of retinal projection to the hypothalamus and the morphological properties of the retinal ganglion cells that comprise the retinohypothalamic tract have been examined in the cat. Intraocular injections of horseradish peroxidase revealed a dense retinal projection to the ventral suprachiasmatic nucleus; however, lighter projections were seen in the dorsal suprachiasmatic nucleus, and in hypothalamic regions both dorsal and lateral to the suprachiasmatic nucleus. Intrasuprachiasmatic nucleus injections of horseradish peroxidase retrogradely labelled retinal ganglion cells that were small to medium in soma size. The labelled ganglion cells exhibited long thin dendrites that were sparsely branched. The labelled retinal ganglion cells exhibited a significant change in soma size associated with retinal eccentricity. The morphological characteristics of the ganglion cells that project to the suprachiasmatic nucleus are similar to those of gamma cells.


Dural involvement in rheumatoid arthritis.
Involvement of the cranial dura in rheumatoid arthritis is rare; a new case of this complication is added to the four recorded instances. Dural involvement in rheumatoid arthritis may occur in the absence of other rheumatoid lesions of the CNS; it appears to take a clinically uneventful course and does not seem to represent a factor predisposing to the development of chronic subdural hematoma.


Transcranial Laser Stimulation as Neuroenhancement for Attention Bias Modification in Adults with Elevated Depression Symptoms.
Low-level light therapy (LLLT) with transcranial laser is a non-invasive form of neuroenhancement shown to regulate neuronal metabolism and cognition. Attention bias modification (ABM) is a cognitive intervention designed to improve depression by decreasing negative attentional bias, but to date its efficacy has been inconclusive. Adjunctive neuroenhancement to augment clinical effectiveness has shown promise, particularly for individuals who respond positively to the primary intervention. This randomized, sham-controlled proof-of-principle study is the first to test the hypothesis that augmentative LLLT will improve the effects of ABM among adults with elevated symptoms of depression. Fifty-one adult participants with elevated symptoms of depression received ABM before and after laser stimulation and were randomized to one of three conditions: right forehead, left forehead, or sham. Participants repeated LLLT two days later and were assessed for depression symptoms one and two weeks later. A significant three-way interaction between LLLT condition, ABM response, and time indicated that right LLLT led to greater symptom improvement among participants whose attention was responsive to ABM (i.e., attention was directed away from negative stimuli). Minimal change in depression was observed in the left and sham LLLT. The beneficial effects of ABM on depression symptoms may be enhanced when paired with adjunctive interventions such as right prefrontal LLLT; however, cognitive response to ABM likely moderates the impact of neuroenhancement. The results suggest that larger clinical trials examining the efficacy of using photoneuromodulation to augment cognitive training are warranted.


The spatial impact of carbon trading on harmonious economic and environmental development: evidence from China.
This research explores the endogenous influence of carbon trading on economic development, the ecological environment, and the coordinated development of both using panel data from 30 Chinese provinces and cities except Tibet from 2007 to 2017. First, we provide environmental production elements to build an economic model based on the endogenous growth model, and then we employ three-dimensional graphics to conduct theoretical derivation in a more accessible and tangible manner. Secondly, we build a comprehensive index of China's coordinated economic and environmental growth in the context of carbon trading and use the coupled coordination model to determine the coordinated coupling degree of each location. Thirdly, the S-DID model is built to investigate the local and geographical implications of carbon trading. The findings demonstrate that the policy has a local impact that is notably favorable on the economic and environmental levels of each Chinese province and the coordinated growth between them. The degree of environmental optimization and the degree of coordinated development between the economy and the environment are two additional areas where the carbon trading mechanism has a strong positive geographical spillover impact. This study adds to the body of knowledge on China's carbon trading system and advances the endogenous growth hypothesis.


Association of Gestational Age at Coronavirus Disease 2019 (COVID-19) Vaccination, History of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection, and a Vaccine Booster Dose With Maternal and Umbilical Cord Antibody Levels at Delivery.
To describe maternal and umbilical cord blood anti-spike immunoglobulin (Ig)G levels at delivery with coronavirus disease 2019 (COVID-19) vaccination before and during pregnancy and to assess the association of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a vaccine booster dose with anti-spike maternal and umbilical cord IgG levels. We conducted a retrospective cohort study of women with self-reported COVID-19 vaccination (Pfizer-BioNTech, Moderna, or Johnson & Johnson/Janssen), including a booster dose, during or before pregnancy, who delivered at 34 weeks of gestation or more. Maternal and umbilical cord blood samples at delivery were analyzed for semi-quantitative anti-spike IgG. We examined the association between timing of maternal vaccination and maternal and umbilical cord anti-spike levels using a rank sum test. The relationships between a prior history of SARS-CoV-2 infection and maternal and umbilical cord anti-spike IgG levels, and between a booster dose and maternal and umbilical cord anti-spike levels, were also evaluated using a rank sum test. We included data from 1,359 vaccinated pregnant women, including 20 women who received a booster dose, and 1,362 umbilical cord samples. Maternal anti-spike IgG levels were detectable at delivery regardless of timing of vaccination throughout pregnancy among fully vaccinated women; however, early third-trimester vaccination was associated with the highest anti-spike IgG levels in maternal and umbilical cord blood. Among women with a history of SARS-CoV-2 infection, maternal and cord blood antibody response achieved with vaccination in early pregnancy was comparable with third-trimester vaccination in pregnant women without a history of SARS-CoV-2 infection. A booster dose in the third trimester was associated with maternal anti-spike IgG levels greater than third-trimester vaccination in women with or without a history of SARS-CoV-2 infection. Vaccination against COVID-19 before and throughout pregnancy was associated with detectable maternal anti-spike IgG levels at delivery. A complete vaccination course, prior history of SARS-CoV-2 infection, and a third-trimester booster dose were associated with the highest maternal and umbilical cord antibody levels.


Perceptions of sense of community and community engagement among rural nurses: Results of a national survey.
Variations in rural nurses' sense of community and engagement in rural communities are poorly understood, although there is evidence that these are linked to community cohesion and perceived community resilience. The aim of our research was to develop descriptive profiles of rural nurses who exhibit a sense of community and community engagement at low, average, and high levels, based on occupational, personal, community, and regional characteristics. These results were linked to levels of cohesion and resilience. A survey questionnaire, including established scales, demographic information, and information about rural nursing practice was administered to rural nurses. Rural communities in all provinces and territories in Canada outside the commuting zone of urban areas with 10,000 or more inhabitants. Multi-level systematic stratified sampling was employed for the national survey. A subsample of 2116 Registered Nurses, Nurse Practitioners, and Licensed Practical Nurses comprised the participants for this analysis. The analysis was conducted in two stages: (1) in the first subset, those (n = 2116) whose primary work community was rural, remote, or rurban with less than 10,000 inhabitants were grouped into a nine-group typology based on low, average, and high tertiles of Psychological Sense of Community and Community Engagement. The second subset (n = 993) represented those in three groups: low-low, average-average, and high-high scores on the two indices. Significant differences between the three groups were identified based on occupational, personal, community, and regional characteristics. Chi Square, ANOVA, and correlation tests were applied as required. Nurses with low scores on both Psychological Sense of Community and Community Engagement were more likely to be from larger communities, single or divorced and living and working in the North. Those with average scores on both scales have been in their nursing positions for more than 20 years, are middle aged and are satisfied with their home community. Nurses in the third group have high scores on both indicators; they are more likely to be from a smaller childhood communities, married or living common-law, and are in the late middle age group. By focusing on the key variables or traits of nurses, modifiable recruitment and retention practices can be implemented. For example, it is important to recruit nurses who are from smaller communities. Other initiatives for nurses include matching community activities with the age and stage of the family and developing a welcoming strategy for the workplace and community for newly arrived nurses.


Involucrin in intraepithelial and invasive squamous cell carcinomas of the cervix: an immunohistochemical study.
Immunohistochemical staining for involucrin, a cytoplasmic protein synthesized during squamous maturation, was assessed in histologic sections from hysterectomy and cone biopsy specimens from patients with cervical neoplasia. In normal and condylomatous squamous epithelium, diffuse cytoplasmic staining was seen in the suprabasal layers, with no staining of the basal cells. Staining was absent in two cases of cervical intraepithelial neoplasia (CIN), grade III, in which the lesions were composed entirely of undifferentiated cells and markedly decreased in cases involving large numbers of basal cells. In 19 of 23 cases (83 per cent) of CIN, however, focal staining for involucrin was seen in large differentiated cells in the more superficial layers, and in two cases of keratinized CIN diffuse suprabasal staining was observed. Similarly, strong staining for involucrin was present in differentiated areas in one case of microinvasive squamous cell carcinoma and in 93 per cent of cases of infiltrating squamous cell carcinoma. These findings suggest that involucrin is a marker for maturation in cervical squamous epithelial neoplasms. Patterns of immunohistochemical staining for involucrin in keratinized dysplasia and differentiated squamous carcinomas should be taken into consideration if loss of involucrin staining is used as a criterion for neoplastic transformation of cervical epithelium, as has been proposed.


Small molecule insulin mimetics reduce food intake and body weight and prevent development of obesity.
Obesity and insulin resistance are major risk factors for a number of metabolic disorders, such as type 2 diabetes mellitus. Insulin has been suggested to function as one of the adiposity signals to the brain for modulation of energy balance. Administration of insulin into the brain reduces food intake and body weight, and mice with a genetic deletion of neuronal insulin receptors are hyperphagic and obese. However, insulin is also an anabolic factor; when administered systemically, pharmacological levels of insulin are associated with body weight gain in patients. In this study, we investigated the efficacy and feasibility of small molecule insulin mimetic compounds to regulate key parameters of energy homeostasis. Central intracerebroventricular (i.c.v.) administration of an insulin mimetic resulted in a dose-dependent reduction of food intake and body weight in rats, and altered the expression of hypothalamic genes known to regulate food intake and body weight. Oral administration of a mimetic in a mouse model of high-fat diet-induced obesity reduced body weight gain, adiposity and insulin resistance. Thus, insulin mimetics have a unique advantage over insulin in the control of body weight and hold potential as a novel anti-obesity treatment.


Infrequent panic attacks: psychiatric comorbidity, personality characteristics and functional disability.
Primary care patients with infrequent panic attacks were found to have similar levels of disability in their social, family and vocational functioning to patients who met DSM-III-R criteria for panic disorder. Both panic subgroups had significantly more functional disability than controls. Patients with panic and infrequent panic had significantly more Axis I psychiatric comorbidity than primary care controls but similar levels of medical comorbidity. Patients with panic disorder had a significantly higher prevalence of one or more other lifetime psychiatric diagnoses, current major depression, and current DSM-III-R depressive symptoms compared to patients with infrequent panic. Patients with infrequent panic scored as high on the NEO personality measure of neuroticism as patients with panic disorder, and both panic subgroups had significantly higher neuroticism levels than controls.


Molecular heterogeneity and new subtypes of HCV genotype 4.
The subtype distribution of HCV genotype 4 was studied in two different African countries, Egypt and Tanzania. The HCV isolates were obtained from epidemiological studies involving, respectively, 135 hepatopatic patients and 1043 pregnant women and outpatients. Sequence comparison and phylogenetic analysis of the NS5b genome region (nt 8327-8499) were performed. Fourteen out of 18 isolates from Egypt, but only 3 out of 6 isolates from Tanzania clustered in the same branch of subtype 4a. Three new proposed subtypes have been identified. The first includes 1 isolate from Egypt (EGY15); the second, 2 isolates from Egypt (EGY193 and EGY44) and 2 isolates from Tanzania (D776, D61); and the third, 1 isolate from Egypt (EGY47) and 1 isolate from Tanzania (D70). These isolates cluster in branches different from any other, corresponding to a known subtype of genotype 4. In conclusion, remarkable genetic heterogeneity has been found among genotype 4 isolates simultaneously circulating in a restricted area. This was particularly observed in the study performed in Tanzania. Potential concern about the sensitivity of diagnostic assays and possible implications in the development of future vaccines have been stressed.


Foreign direct investment, stock market capitalization, and sustainable development: relative impacts of domestic and foreign capital.
It is well acknowledged that achieving sustainable development goals without negatively impacting a country's economic activity is complicated. The question of whether foreign or domestic capital can be used to address the financial demands of the nations who lack the financial resources for a green transformation should now be resolved. Based on this, the main goal of this research is to analyze the impacts of domestic and foreign capital on carbon emissions for a heterogeneous panel of 42 countries for the period from 1990 to 2017. Aside from capital accumulation, the environmental impact of elements such as economic growth, urbanization, trade openness, and energy usage is also studied. The newly developed quantile via moment approach is utilized to isolate the impacts according to the countries' emission levels. Finally, the impact of these variables on the recently constructed sustainable development index is investigated in order to ensure its robustness. The findings of the study reveal that the environmental efficiency of domestic capital accumulation in countries with low emission levels is higher than in countries with high emission levels. Foreign capital, on the other hand, has no substantial effect on emission levels in all quantiles.


Modifiable risk factors for erectile dysfunction: an assessment of the awareness of such factors in patients suffering from ischaemic heart disease.
Up to 40% of cases of erectile dysfunction (ED) originate from vascular disturbances associated with atherosclerotic disease, leading to the previously proven concomitance between ischaemic heart disease (IHD) and ED. The aim of this study was to evaluate patients' knowledge about modifiable risk factors for ED. The evaluated group of patients was composed of 502 male patients undergoing cardiac rehabilitation and receiving treatment for IHD. The patients' knowledge of risk factors for ED linked to IHD was assessed with an original survey. The presence of ED was assessed using an abridged version of the International Index of Erectile Function-5 questionnaire. Increase in leisure-time physical activity was estimated using a leaflet based on the Framingham questionnaire. In all, 189 participants were unable to name any modifiable ED risk factors, and only 31 patients knew all 6 of them. The most frequently mentioned ED risk factor was smoking, whereas the least frequently mentioned was sedentary lifestyle. Awareness of smoking as an ED risk factor was closely related to the patients' level of education, place of residence, smoking and underlying ED in the individual patient. The ability to classify diabetes as a risk factor for ED was significantly related to the patients' level of education, place of residence, and the prevalence of diabetes in the evaluated group of respondents. The same relations were observed regarding hyperlipidaemia. Awareness of the negative impact a sedentary lifestyle has on the erectile process was found to be closely related to the patients' age, as well as their level of education. The performed study demonstrates the poor knowledge of IHD patients about the modifiable risk factors for ED. The factor that patients are the least aware of is sedentary lifestyle, which, simultaneously, is the risk factor that most frequently affects the respondents.


Cassette mutagenesis: an efficient method for generation of multiple mutations at defined sites.
A method is described for the efficient insertion of mutagenic oligodeoxynucleotide cassettes which allow saturation of a target amino acid codon with multiple mutations. Restriction sites are introduced by oligonucleotide-directed mutagenesis procedures to flank closely the target codon in the plasmid containing the gene. The restriction sites to be introduced are chosen based on their uniqueness to the plasmid, proximity to the target codon and conservation of the final amino acid coding sequence. The flanking restriction sites in the plasmid are digested with the cognate restriction enzymes, and short synthetic duplex DNA cassettes (10-25 bp) are inserted. The mutagenic cassette is designed to restore fully the wild-type coding sequence, except over the target codon, and to eliminate one or both restriction sites. Elimination of a restriction site facilitates selection of clones containing the mutagenic oligodeoxynucleotide cassette. To make the cassettes, single-stranded oligodeoxynucleotides and their complements are synthesized in separate pools containing different codons over the target. This method has been successfully applied to generate 19 amino acid substitutions at position 222 in the subtilisin protein sequence.


Mean arterial pressure, fitness, and executive function in middle age and older adults.
Previous literature suggests that higher fitness is related to better executive function in older adulthood, but the mechanisms underlying this association are poorly understood. While many studies have focused on these associations in older adulthood, recent evidence suggests the importance of cardiorespiratory fitness (CRF) and long-term blood pressure control on cognitive functioning. The purpose of the current study was to examine whether mean arterial pressure (MAP) mediated the association between CRF and executive function in middle age and older adults. Participants were adults (age 40+) without any self-reported psychiatric and neurological disorders or cognitive impairment from the Nathan Kline Institute Rockland Sample (N = 224, M age = 56). CRF was defined by V̇O2max estimated via a bike test, neuropsychological testing was used to examine executive functioning, and MAP was calculated from systolic and diastolic blood pressure recordings. Mediation models were analyzed controlling for age, sex, and education. Results indicated that higher CRF was associated with better inhibition (B = -0.0048, t = -2.16, p = 0.03) and there was a significant indirect effect of greater CRF on better inhibition through lower MAP (B = -0.0011; CI [-0.0026, -0.0002]). There were additional significant indirect effects of greater CRF and better fluency (B = 0.0028; CI [.0009, 0.0053]) and planning (B = 0.0037; CI [.0014, 0.0074]) through lower MAP. This suggests that MAP may be an underlaying physiological mechanism by which CRF influences executive function in mid- and older adulthood.


E-cadherin expression is homogeneously reduced in adenoma from patients with familial adenomatous polyposis: an immunohistochemical study of E-cadherin, beta-catenin and cyclooxygenase-2 expression.
The adenomatous polyposis coli (APC) protein plays a crucial role in the regulation of beta-catenin, which is linked to the cell adhesion molecule E-cadherin. Furthermore, beta-catenin and cyclooxygenase-2 (COX-2) are both involved in the activation of nuclear transcription factors inducing cell proliferation. Germline mutations in the APC gene are the cause of familial adenomatous polyposis (FAP). To characterise the expression pattern of these proteins in FAP in comparison with sporadic adenomas, we studied 18 FAP-associated adenomas, 16 sporadic adenomas and seven normal colonic controls. E-cadherin, beta-catenin, COX-2 expression and the proliferative index (Ki67) were assessed by immunohistochemistry (index of expressing cells / total number of cells) in adenomatous mucosa, adjacent non-neoplastic tissue and normal colonic controls. E-cadherin expression was significantly and homogeneously reduced in FAP adenomas (24%; 95%CI 16-32; sporadic adenomas 61%; 38-84; normal controls 98%; 96-100). Membraneous beta-catenin expression was significantly reduced in both FAP (30%; 11-49) and sporadic (42%; 19-65) adenomas (normal controls 96%; 88-104), whereas marked nuclear staining occurred in sporadic, but not in FAP adenomas. Stromal COX-2 expression and the proliferative index were increased only in sporadic adenomas (sporadic adenomas: COX-2 12%; 7-17, Ki67 24%; 15-33, FAP adenomas: COX-2 8%; 5-11, Ki67 5%; 2-9, normal controls: COX-2 4%; 2-7, Ki67 6%; 1-11). Proteins involved in cell adhesion and cell proliferation, especially E-cadherin, are expressed differently in FAP and sporadic adenoma, pointing to possible differences in the molecular pathways to adenoma.


Immunochemical characterization of Candida albicans cell wall antigens: specific determinant of Candida albicans serotype A mannan.
We investigated the chemical structure of the specific determinant in the mannan of Candida albicans M-1012 (serotype A) strain. Acetolysis of the mannan, obtained by alkali extraction and purified as the copper complex, gave mannose and six oligosaccharides (from di- to hexasaccharide) and a small amount of a heptasaccharide. We examined the inhibition by these oligosaccharides up to hexaose of the precipitin reaction between anti-factor 6 serum specific for serotype A and homologous mannan, and found that the mannohexaose was the most effective inhibitor. These, and results obtained by proton magnetic resonance (PMR) spectroscopy, methylation analysis, and other structural studies, suggest that the main component of this hexaose consists of one terminal alpha (1-3) linkage in addition to four alpha (1-2) linkages, and that this alpha (1-3)-containing mannohexaose may be responsible for the specificity of antigenic factor 6. Further results obtained by analyses of polarimetry, PMR spectroscopy, and chromium trioxide oxidation-methylation of C. albicans M-1012 mannan has a beta-linkage in addition to alpha-linkages, and that the mode of the beta-linkage is mainly (1-6) linkage. Further evidence obtained by Smith degradation-methylation analysis and by quantitative precipitin reactions of intact and acid-degraded mannan suggests that the antigenic determinant of antigenic factor 6 may be bound, via the beta (1-6) linkage, to C-6 of mannose residues involved in oligosaccharide side chains of serotype A mannan.


Possibilities to improve automation, speed and precision of proteome analysis: a comparison of two-dimensional electrophoresis and alternatives.
Proteome analysis requires fast methods with high separation efficiencies in order to screen the various cell and tissue types for their proteome expression and monitor the effect of environmental conditions and time on this expression. The established two-dimensional gel electrophoresis (2-DE) is by far too slow for a consequential screening. Moreover, it is not precise enough to observe changes in protein concentrations. There are various approaches that promise faster, automated proteome analysis. This article concentrates on capillary (CT isoelectric focusing coupled to mass spectrometry (CIEF-MSn) and preparative IEF followed by size-exclusion chromatography, hyphenated with MS (PIEF-SEC-MS). These two approaches provide a similar separation pattern as the established 2-DE technique and therefore allow for the continued use of data based on this traditional approach. Their performances have been discussed and compared to 2-DE, evaluating 169 recent articles. Data on analysis time, automation, the detection limit, quantitation, peak capacity, mass and pI accuracy, as well as on the required sample amount are compared in a table.


Characterization of the mobility of various chemical groups in the purple membrane of Halobacterium halobium by 13C, 31P and 2H solid state NMR.
Lyophilized purple membrane sheets have been investigated by C-13- and P-31-cross polarization/magic angle spinning NMR spectroscopy. The high-resolution C-13 spectrum and its non-quaternary suppression version indicate fast protein side-chain motions but a rigid backbone structure on a time scale of roughly less than 0.001 to 0.01 s. Three components of exchangeable hydrogen have been detected by deuterium NMR. The mean exchange time of the peptide hydrogens must be longer than 1 microsecond. The medium component is attributed to mobile side-chains. In addition a narrow line has been observed which is assigned to the residual hydration water.


Severity and Variability of Depression Symptoms Predicting Suicide Attempt in High-Risk Individuals.
Predicting suicidal behavior continues to be among the most challenging tasks in psychiatry. To examine the trajectories of clinical predictors of suicide attempt (specifically, depression symptoms, hopelessness, impulsivity, aggression, impulsive aggression, and irritability) for their ability to predict suicide attempt and to compute a risk score for suicide attempts. This is a longitudinal study of the offspring of parents (or probands) with mood disorders who were recruited from inpatient units at Western Psychiatric Institute and Clinic (Pittsburgh) and New York State Psychiatric Institute. Participants were recruited from July 15, 1997, to September 6, 2005, and were followed up through January 21, 2014. Probands and offspring (n = 663) were interviewed at baseline and at yearly follow-ups for 12 years. Lifetime and current psychiatric disorders were assessed, and self-reported questionnaires were administered. Model evaluation used 10-fold cross-validation, which split the entire data set into 10 equal parts, fit the model to 90% of the data (training set), and assessed it on the remaining 10% (test set) and repeated that process 10 times. Preliminary analyses were performed from July 20, 2015, to October 5, 2016. Additional analyses were conducted from July 26, 2017, to July 24, 2018. The broad definition of suicide attempt included actual, interrupted, and aborted attempts as well as suicidal ideation that prompted emergency referrals during the study. The narrow definition referred to actual attempt only. The sample of offspring (n = 663) was almost equally distributed by sex (316 female [47.7%]) and had a mean (SD) age of 23.8 (8.5) years at the time of censored observations. Among the 663 offspring, 71 (10.7%) had suicide attempts over the course of the study. The trajectory of depression symptoms with the highest mean scores and variability over time was the only trajectory to predict suicide attempt (odds ratio [OR], 4.72; 95% CI, 1.47-15.21; P = .01). In addition, we identified the following predictors: younger age (OR, 0.82; 95% CI, 0.74-0.90; P < .001), lifetime history of unipolar disorder (OR, 4.71; 95% CI, 1.63-13.58; P = .004), lifetime history of bipolar disorder (OR, 3.4; 95% CI, 0.96-12.04; P = .06), history of childhood abuse (OR, 2.98; 95% CI, 1.40-6.38; P = .01), and proband actual attempt (OR, 2.24; 95% CI, 1.06-4.75; P = .04). Endorsing a score of 3 or higher on the risk score tool resulted in high sensitivity (87.3%) and moderate specificity (63%; area under the curve = 0.80). The specific predictors of suicide attempt identified are those that clinicians already assess during routine psychiatric evaluations; monitoring and treating depression symptoms to reduce their severity and fluctuation may attenuate the risk for suicidal behavior.


Experimental non-ATP-competitive therapies for chronic myelogenous leukemia.
Chronic myelogenous leukemia (CML) is a hematopoietic stem cell malignancy driven by the BCR-ABL fusion tyrosine kinase. The central role played by BCR-ABL1 in the pathogenesis of CML facilitated the development of the tyrosine kinase inhibitor (TKI) imatinib mesylate, the first actual targeted therapy in cancer history. Imatinib competes with ATP at the active site of BCR-ABL1 kinase. Despite outstanding clinical results, imatinib as well as other BCR-ABL1 TKIs have been associated with limited rates of complete molecular response and the development of mutations within the kinase domain of BCR-ABL1 that impairs TKI binding. To override such drawbacks, an array of novel non-ATP-competitive therapies with distinct mechanisms of action is undergoing preclinical, and in some cases, early clinical stages of development. This review focuses on the most promising among such therapeutics.


Free gingival grafting and vestibuloplasty with endosseous implant placement: clinical report.
Soft-tissue complications may occur adjacent to endosseous implants and their associated transepithelial abutments. Vestibuloplasty and connective tissue grafting techniques can be used to obtain attached keratinized tissue in the anterior endentulous mandible before implant placement in an effort to improve the long-term prognosis. A clinical case is presented that was restored with a mandibular implant-supported, bar-retained overdenture opposing a maxillary complete denture after grafting and vestibuloplasty procedures.


Prenatal diagnosis and management of monozygotic twins discordant for severe fetal abnormalities.
We present prenatal diagnosis and management of monozygotic (MZ) twins discordant for severe fetal abnormalities. A 36-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, and hydrops fetalis, a giant cystic hygroma of 5 × 3.5 cm and left hydronephrosis in a co-twin. The other co-twin was structurally normal. Amniocentesis revealed a karyotype of 46,XY in both co-twins. Simultaneous polymorphic DNA marker analysis using the DNAs extracted from maternal blood and uncultured amniocytes confirmed MZ twinning. The woman underwent a successful selective fetal reduction by radiofrequency ablation at 22 weeks of gestation. At 28 weeks of gestation, premature rupture of membranes occurred, and a 1280-g normal male baby and a 275-g dead malformed co-twin were delivered. The normal co-twin was phenotypically normal and was doing well at age seven weeks. Prenatal diagnosis of MZ twins discordant for structural abnormalities should include a differential diagnosis of MZ twinning, and a zygosity test is necessary under such a circumstance.


Intravesical Pseudomonas aeruginosa mannose-sensitive Hemagglutinin vaccine triggers a tumor-preventing immune environment in an orthotopic mouse bladder cancer model.
Bacillus Calmette-Guerin (BCG) immunotherapy can prevent recurrence and progression in selected patients with non-muscle-invasive bladder cancer (NMIBC); however, significant adverse events and treatment failure suggest the need for alternative agents. A commercial anti-infection vaccine comprises a genetically engineered heat-killed Pseudomonas aeruginosa (PA) expressing many mannose-sensitive hemagglutination (MSHA) fimbriae, termed PA-MSHA, which could be a candidate for bladder cancer intravesical therapy. In an immunocompetent orthotopic MB49 bladder cancer model, we characterized the antitumor effects and mechanisms of PA-MSHA compared with those of BCG. Three weekly intravesical PA-MSHA or BCG treatments reduced tumor involvement; however, only PA-MSHA prolonged survival against MB49 implantation significantly. In non-tumor-bearing mice after treatment, flow-cytometry analysis showed PA-MSHA and BCG induced an increased CD4/CD8 ratio, the levels of effector memory T cell phenotypes (CD44, CXCR-3, and IFN-γ), and the proportion of CD11b+Ly6G-Ly6C-IA/IE+ mature macrophages, but a decrease in the proportion of CD11b+Ly6G-Ly6C+IA/IE- monocytic myeloid-derived suppressor cells (Mo-MDSCs) and the expression of suppressive molecules on immune cells (PD-L1, PD-1, TIM-3, and LAG-3). Notably, PA-MSHA, but not BCG, significantly reduced PD-1 and TIM-3 expression on CD4+ T cells, which might account for the better effects of PA-MSHA than BCG. However, in tumor-bearing mice after treatment, the increased proportion of Mo-MDSCs and high expression of PD-L1 might be involved in treatment failure. Thus, modulating the balance among adaptive and innate immune responses was identified as a key process underlying PA-MSHA-mediated treatment efficacy. The results demonstrated mechanisms underlying intravesical PA-MSHA therapy, pointing at its potential as an alternative effective treatment for NMIBC.


Significance of eosinophil counting in tumor associated tissue eosinophilia (TATE).
Eosinophils are present in large numbers in some squamous cell carcinomas of the oral cavity. Whilst it is proposed that they have an 'immuno-protective' effect, this remains unproven. The contradictory reports may be due to inconsistencies in eosinophil counting. Eighty-one cases of squamous cell carcinoma (SSC) of oral tongue were examined. Two methods of eosinophil counting were performed. In the first method (classical), the eosinophils were counted per 10 HPF. In the second method (our so-called density method), the highest eosinophil density per surface area was counted for each case. The two methods were correlated. Using the classical method a number of fields in cases ranked low, contained more than 10 eosinophils. Likewise, some moderate cases contained more than 100 eosinophils. There is poor correlation between the classical and density counts. Nevertheless, good correlation between the two methods could be achieved if the boundaries of the classical method are modified. Eosinophils invariably appear in clusters. We feel that an assessment of density may well be better than classical counting, and have more relationship with function.


A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury.
It is not clear what kind of drug is appropriate to heal NSAID-induced enteropathy. Several reports showed the preventive effect of prostaglandin analogue or inducer using healthy subjects who took NSAIDs. However there was no report for healing effect and for patients. The aim of this study was to evaluate the healing effect of rebamipide in patients with NSAIDs-induced enteropathy. In addition, we evaluated for nutritional parameter. This study was conducted as a randomized, double-blinded, placebo-controlled, multicenter trial. Study protocol was approved by each hospital's ethical committees. Patients with LDA and/or NSAID more than 3 months were enrolled. Patients with enteropathy were divided into the placebo and the rebamipide groups. Rebamipide 100 mg three times daily was administered during 4 weeks. Capsule endoscopies were performed at 0 and 4 week. The number of small intestinal ulcer and erosion were evaluated. Total protein was analyzed as nutritional parameter. Sixty one participants were completed this study. Change in number of small intestinal erosion in the rebamipide group was -2.5 ± 3.4, and 2.1 ± 3.9 in the placebo group (P < 0.0001). Change in number of small intestinal ulcer in the rebamipide group was -0.5 ± 1.6, and 0.1 ± 0.7 in the placebo group (P = 0.024). Change in serum total protein levels in the rebamipide group was 0.06 ± 0.36, and -0.27 ± 0.34 in the placebo group (P = 0.0005). Rebamipide has not only the healing effect for NSAIDs-induced enteropathy compared with placebo, but the improvement of nutritional condition. These results showed a tentative therapeutical strategy for chronic NSAIDs users.


High-affinity chimeric anti-(colorectal carcinoma) antibody correlated to enhanced tumor targeting in biodistribution and imaging.
The genetically engineered chimeric cB72.3m4 and cB72.3m12 antibodies recognize the same tumor-associated TAG72 antigen. The high-affinity cB72.3m4 antibody had an approximately 18-fold higher affinity constant for the TAG72 antigen than the low-affinity cB72.3m12 antibody. The relationship between antibody affinity and tumor targeting was studied by using these two antibodies. In biodistribution and imaging studies in athymic mice bearing LS174T human colon cancer xenografts, the radiolabelled high-affinity cB72.3m4 antibody was rapidly cleared from the blood, whereas the low-affinity cB72.3m12 antibody had slower blood clearance. The data showed that the high-affinity cB72.3m4 antibody appeared to localize more in tumors (based on tumor:normal-tissue ratios) than did the low-affinity cB72.3m12 antibody, and enhanced the target-to-nontarget image contrast. This study provides evidence that the high-affinity chimeric antibody cB72.3m4 may be useful in both immunodetection and immunotherapy of cancer.


SEALS: an Innovative Pipeline Program Targeting Obstacles to Diversity in the Physician Workforce.
Medical schools may find implementing pipeline programs for minority pre-medical students prohibitive due to a number of factors including the lack of well-described programs in the literature, the limited evidence for program development, and institutional financial barriers. Our goals were to (1) design a pipeline program based on educational theory; (2) deliver the program in a low cost, sustainable manner; and (3) evaluate intermediate outcomes of the program. SEALS is a 6-week program based on an asset bundles model designed to promote: (1) socialization and professionalism, (2) education in science learning tools, (3) acquisition of finance literacy, (4) the leveraging of mentorship and networks, and (5) social expectations and resilience, among minority pre-medical students. This is a prospective mixed methods study. Students completed survey instruments pre-program, post-program, and 6 months post-program, establishing intermediate outcome measures. Thirteen students matriculated to SEALS. The SEALS cohort rated themselves as improved or significantly improved when asked to rate their familiarity with MCAT components (p < 0.01), ability to ask for a letter of recommendation (p = 0.04), and importance of interview skills (p = 0.04) compared with before the program. Over 90 % of students referenced the health disparities lecture series as an inspiration to advocate for minority health. Six-month surveys suggested that SEALS students acquired and applied four of the five assets at their college campuses. This low-cost, high-quality, program can be undertaken by medical schools interested in promoting a diverse workforce that may ultimately begin to address and reduce health care disparities.


A review of cannabis allergy in the early days of legalization.
Cannabis allergy is a burgeoning field; consequently, research is still in its infancy and allergists' knowledge surrounding this topic is limited. As cannabis legalization expands across the world, it is anticipated that there will be an increase in cannabis use. Thus, we hypothesize that a concomitant rise in the incidence of allergy to this plant can be expected. Initiatives aimed at properly educating health care professionals are therefore necessary. This review presents the most up-to-date information on a broad range of topics related to cannabis allergy. Although the clinical features of cannabis allergy are becoming more well described and recognized, the tools available to make a correct diagnosis are meager and often poorly accessible. In addition, research on cannabis allergy is still taking its first steps, and new and potentially groundbreaking findings in this field are expected to occur in the next few years. Finally, although therapeutic approaches are being developed, patient and physician education regarding cannabis allergy is certainly needed.


Protocol for using single-cell sequencing to study the heterogeneity of NF1 nerve sheath tumors from clinical biospecimens.
Single-cell sequencing is a powerful technology to understand the heterogeneity of clinical biospecimens. Here, we present a protocol for obtaining single-cell suspension from neurofibromatosis type 1-associated nerve sheath tumors for transcriptomic profiling on the 10x platform. We describe steps for clinical sample collection, generation of single-cell suspension, and cell capture and sequencing. We then detail methods for integrative analysis, developmental Schwann cell trajectory building using bioinformatic tools, and comparative analysis. This protocol can be adapted for single-cell sequencing using mouse nerve tumors. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1.


Detectability and criterion measures in temporal generalization.
Computer simulation of performance on "normal" and "episodic" temporal generalization tasks was used to examine the relations between the theoretical parameters of models which fit temporal generalization data ("timing sensitivity" and "threshold"), and the d' (detectability) and beta (decision criterion) measures of signal-detection theory. In general, changes in timing sensitivity altered d', whereas threshold changes affected beta, supporting the assertion that the two sorts of variables ("sensitivity/detectability" and "threshold/criterion") were psychologically equivalent. Cases where temporal generalization gradients were apparently contaminated by "random responding" could be treated by changes in beta, but cases in which temporal generalization gradients were not peaked at the standard posed severe problems for a simple signal-detection account, although existing models of temporal generalization performance could deal with them.


Determination of n-alkanes contamination in soil samples by micro gas chromatography functionalized by multi-walled carbon nanotubes.
A new method for separation of 11 n-alkanes: octane, o-nonane, n-decane, n-undecane, n-dodecane, n-tridecane, n-tetradecane, n-pentdecne, n-hexadecath, heptadecane, n-octadecane in soil samples was developed. Kuderna-Danish (K.D.) concentrator enrichment prior to ultrasonic extraction and the silicone chromatography column purification and with gas chromatography flame ionization detection (GC-FID) could be used for n-alkanes determination. The micro channels of open tubular column were fabricated onto a silicon wafer to replace the quartz capillary chromatographic column. The column structure and analysis parameters that affected the column separation were investigated and optimized. Under optimal conditions, the extract reagent was centrifuged and collected. A silicone chromatography column and a K.D. concentrator were used for further clean-up and enrichment. Using this method, the limits of detection (LOD) and limits of quantification (LOQ) were obtained in the range of 0.03-0.15 and 0.1-0.5 mg kg(-1) in soil samples, respectively. The relative standard deviation (RSD) was under 12%. The optimized procedure that presented good analytical performance (with recoveries ranging from 56.5% to 89.2%), was successfully applied to determine n-alkane content in farmland soil samples adjacent to a highway. The results showed that the MWCNTs-functionalized column is capable of separating the alkane contaminations with high resolution in about 3 min, which is much shorter than that of GC-MS and other conventional analytical methods, demonstrating its great potential for rapid analysis.


Zoonotic disease and virome diversity in bats.
The emergence of zoonotic viral diseases in humans commonly reflects exposure to mammalian wildlife. Bats (order Chiroptera) are arguably the most important mammalian reservoir for zoonotic viruses, with notable examples including Severe Acute Respiratory Syndrome coronaviruses 1 and 2, Middle East Respiratory Syndrome coronavirus, henipaviruses and lyssaviruses. Herein, we outline our current knowledge on the diversity of bat viromes, particularly through the lens of metagenomic next-generation sequencing and in the context of disease emergence. A key conclusion is that although bats harbour abundant virus diversity, the vast majority of bat viruses have not emerged to cause disease in new hosts such that bats are better regarded as critical but endangered components of global ecosystems.


Comparison of conventional fast spin echo, single-shot two-dimensional and three-dimensional half-fourier RARE for T2-weighted female pelvic imaging.
To evaluate the usefulness of the three-dimensional half-Fourier RARE sequence in comparison with single-shot two-dimensional half-Fourier RARE and conventional fast spin echo (FSE) for female pelvic imaging. Imaging with all sequences was performed in 146 patients with 166 focal lesions on a 1.5-T system. The images were compared on the basis of quality, lesion conspicuity, and lesion to the uterus contrast-to-noise ratio (CNR). The sharpness of intrapelvic organs on the three-dimensional half-Fourier RARE sequence was better than that on two-dimensional half-Fourier RARE and worse than that on FSE. Motion-related artifacts for three-dimensional half-Fourier RARE were more frequent than those for two-dimensional half-Fourier RARE. There was no statistical difference between the three-dimensional half-Fourier RARE sequence and FSE in regard to lesion conspicuity and overall image quality. The CNR of leiomyoma to myometrium and cervical cancer to cervical stroma was the highest with three-dimensional half-Fourier RARE (P< 0.05). The three-dimensional half-Fourier RARE sequence generates images with higher contrast and better image resolution than two-dimensional-RARE. The three-dimensional data set provided images that can be observed in any orientation without acquiring an additional scan by using the multiplanar reconstruction (MPR) method.


A systematic literature review on unnecessary diagnostic testing: The role of ICT use.
The negative impact of unnecessary diagnostic tests on healthcare systems and patients has been widely recognized. Medical researchers in various countries have been devoting effort to reduce unnecessary diagnostic tests by using different types of interventions, including information and communications technology-based (ICT-based) intervention, educational intervention, audit and feedback, the introduction of guidelines or protocols, and the reward and punishment of staff. We conducted a review of ICT based interventions and a comparative analysis of their relative effectiveness in reducing unnecessary tests. A systematic Boolean search in PubMed, EMBase and EBSCOhost research databases was performed. Keyword search and citation analysis were also conducted. Empirical studies reporting ICT based interventions, and their implications on relative effectiveness in reducing unnecessary diagnostic tests (pathology tests or medical imaging) were evaluated independently by two reviewers based on a rigorously developed coding protocol. 92 research articles from peer-reviewed journals were identified as eligible. 47 studies involved a single-method intervention and 45 involved multi-method interventions. Regardless of the number of interventions involved in the studies, ICT-based interventions were utilized by 71 studies and 59 of them were shown to be effective in reducing unnecessary testing. A clinical decision support (CDS) tool appeared to be the most adopted ICT approach, with 46 out of 71 studies using CDS tools. The CDS tool showed effectiveness in reducing test volume in 38 studies and reducing cost in 24 studies. This review investigated five frequently utilized intervention methods, ICT-based, education, introduction of guidelines or protocols, audit and feedback, and reward and punishment. It provides in-depth analysis of the efficacy of different types of interventions and sheds insights about the benefits of ICT based interventions, especially those utilising CDS tools, to reduce unnecessary diagnostic testing. The replicability of the studies is limited due to the heterogeneity of the studies in terms of context, study design, and targeted types of tests.


The effect of exercise and improved physical fitness on basal metabolic rate.
1. The suggestion that there is a sustained enhancement in metabolic rate after exercise was investigated during the course of a study in which six normal-weight volunteers (three men, three women) took part in a 9-week training programme. Baseline values were assessed in a 3-5 week control period of minimal activity before training. At the end of the study the subjects were capable of running for 1 h/d, 5 d/week. 2. Throughout the entire study the subjects were maintained on a constant diet. Measurement of energy expenditure by the doubly-labelled water (2H2(18)O) method showed that the subjects had an energy imbalance of +3% in the control and -20% at the end of the training period. The subjects were in positive (1.1 (SE 0.2) g) nitrogen balance in the second week of the control, and in negative (-0.6 (SE 0.3) g) N balance in the last week of the exercise period. 3. Over the course of the study maximum oxygen consumption (VO2max) and high-density-lipoprotein-cholesterol levels increased by 30%. Heart rate at rest and when performing a standard step test fell significantly. 4. Body composition was assessed weekly by 40K counting and skinfold thickness measurements, in addition to 2H2 dilution at the beginning and end of the study. Fat-free mass was apparently gained in the early phases of the study, but there was lack of agreement between the different methods of assessing body composition. Changes in body-weight were not significant. 5. Basal metabolic rate (BMR), overnight metabolic rate (OMR) and sleeping metabolic rate (SMR) were measured on three occasions: in the control period, and the beginning and end of the training periods. Average BMR in the control period was 5.91 (SE 0.39) MJ/24 h and was not changed with activity. There were no changes in OMR (5.71 (SE 0.27) MJ/24 h in the control) nor in SMR (5.18 (SE 0.27) MJ/24 h in the control), nor in BMR, OMR or SMR when expressed per kg body-weight, or per kg fat-free mass. 6. These results do not support the suggestions that there is a sustained increase in BMR following exercise that can usefully assist in weight-loss programmes.


Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease.
Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease, characterised by fluctuating muscle weakness which makes it challenging to assess symptom severity. Mixed methods psychometrics (MMP), which combines evidence from qualitative research and modern psychometrics, is a versatile approach to the development of patient-centred outcome measures (PCOM) in the context of rare disease. Our objective was to develop the MG Symptom patient-reported outcome (PRO) to assess key aspects of MG severity from the patient perspective. We used MMP to develop a novel PRO instrument in a multi-step process. An initial conceptual model for MG patient experience was developed and expanded based on preliminary literature review and two waves of concept elicitation interviews with people with MG (Step 1). Based on this, the novel PRO instrument, the MG Symptoms PRO, was drafted. The draft instrument was refined by combining qualitative and quantitative data collected in a Phase 2 clinical study (Step 2). Findings from the literature review and concept elicitation interviews (n = 96) indicated that patient experience in MG includes proximal muscle weakness symptoms related to several body parts, along with muscle weakness fatigability and general fatigue. Then, a set of 42 items across five scales (ocular-, bulbar-, and respiratory muscle weakness, physical fatigue, and muscle weakness fatigability) was developed. Qualitative evidence endorsed its relevance, clarity, and ease of completion; quantitative analysis with Rasch measurement theory methods demonstrated strong measurement properties, including good targeting and high reliability. Classical test theory analyses showed adequate reliability of the instrument and mild to moderate correlations with other widely used MG-specific outcome measures. The MG Symptoms PRO has potential to be used both to measure treatment benefit in clinical trials and monitor symptom severity in clinical practice. Its component scales were purposefully designed to stand alone, enhancing interpretability of scores given the heterogeneity of MG, and enabling modular use. Compared with existing MG PROs, it contains more detailed assessments of muscle weakness and muscle weakness fatigability symptoms, which are of key importance to people with MG. The MMP approach used may serve as a case study for developing PCOMs across rare disease indications.


Prophylactic negative pressure wound therapy in colorectal surgery. Effects on surgical site events: current status and call to action.
Surgical site events, including surgical site infections (SSI), represent a major problem in general surgery. SSI are responsible of nuisance for patients, and can lead to important complications and disability, often needing prolonged postoperative stay with specific treatment and recovery in Intensive Care Units. These justify the higher costs due to SSI. Despite the growing body of evidence concerning SSI in general surgery, literature dealing with SSI after colorectal surgery is scarce, reflecting in suboptimal perception of such a relevant issue by colorectal surgeons and health authorities in Italy, though colorectal surgery is associated with higher rates of SSI. The best strategy for reducing the impact of SSI on costs of care and patients quality of life would be the development of a preventive bundle, similar to that adopted in the US through the colorectal section of the National Surgery Quality Improvement Project of the American College of Surgeons (ACS-NSQIP). This policy has been showed to significantly reduce the rates of SSI. In this scenario, incisional negative pressure wound therapy (NPWT) is likely to play a pivotal role. We herein reviewed the literature to report on the current status of preventive NPWT on surgical wounds of patients undergoing colorectal procedures with primary wound closure, suggesting evidence-based measures to reduce the impact of SSI, and to contain the costs associated with conventional NPWT devices by means of newer available technologies. Some explicative real life cases are presented.


A comprehensive catalogue of polyketide synthase gene clusters in lichenizing fungi.
Lichens are fungi that form symbiotic partnerships with algae. Although lichens produce diverse polyketides, difficulties in establishing and maintaining lichen cultures have prohibited detailed studies of their biosynthetic pathways. Creative, albeit non-definitive, methods have been developed to assign function to biosynthetic gene clusters in lieu of techniques such as gene knockout and heterologous expressions that are commonly applied to easily cultivatable organisms. We review a total of 81 completely sequenced polyketide synthase (PKS) genes from lichenizing fungi, comprising to our best efforts all complete and reported PKS genes in lichenizing fungi to date. This review provides an overview of the approaches used to locate and sequence PKS genes in lichen genomes, current approaches to assign function to lichen PKS gene clusters, and what polyketides are proposed to be biosynthesized by these PKS. We conclude with remarks on prospects for genomics-based natural products discovery in lichens. We hope that this review will serve as a guide to ongoing research efforts on polyketide biosynthesis in lichenizing fungi.


Efficacy of specialist versus non-specialist management of spinal cord injury within the UK.
Retrospective outcome measurement study. Spinal cord injury (SCI) represents a life changing multi-factorial event for persons sustaining this condition. There has been anecdotal evidence that some persons sustaining this condition in the UK have not been managed within one of the 11 national specialist spinal injury units (SIU) but rather are managed in non-specialist rehabilitation areas. This study aimed to ascertain if differences in outcome from health, functional and social perspectives exists between the two cohorts. All participants had received rehabilitation within the UK National Health Service. A sample of 800 participants were recruited from the database of the Spinal Injury Association (UK) to complete a postal, self reporting questionnaire ascertaining perceived outcome across all of these perspectives. Despite having more severe injuries, the SIU cohort demonstrated statistically significant improved outcomes in 10 out of 18 health outcomes, 16 out of 18 functional outcomes and five out of 10 social outcomes in comparison with the non-SIU cohort. This study provides the evidence that people with SCI are better managed through a specialist system. Should a like for like comparison have been made as regards severity (completeness) of injury, the likelihood is that the results would have been even more in favour of the SIU cohort. These results should encourage commissioners of health care and those working in trauma settings to ensure people with SCI are managed in a specialist spinal injury unit setting both nationally and internationally.


[Polish version of the Revised Hallucination Scale (RHS) by Morrison et al. Its factor analysis and the prevalence of hallucinatory-like experiences among healthy participants].
The study aimed at presenting the Polish version of Morrison's et al. (2002) Revised Hallucinations Scale (RHS). Factor structure of the RHS was of interests. Moreover, we were interested in the incidence of hallucinatory-like experiences among healthy subjects. Polish version of RHS was elaborated following the back-translation procedure. Then, it was administered to 213 healthy persons. Factor structure analysis of RHS was conducted. Finally, based on the RHS scores, frequency of selected visual and auditory hallucinatory like experiences were calculated. Factor analysis of RHS revealed four factors structure: 1) imagery vividness; 2) auditory and visual perceptual anomalies; 3) experience of dissociation; 4) auditory hallucinatory like experiences. Four factors explained 51.54% of total variance in the RHS. The scale has good reliability (Cronbach's alpha varied from 0.7 to 0.88). Frequency of selected auditory hallucinatory like experiences varies from several to a dozen percent. Similar results were revealed for visual hallucinatory like experiences. These experiences that are similar to hallucinations observed among psychotic patients were observed seldom. The factor structure of Polish versions of the RHS is comparable to the original one. However, we have found a new subscale that may represent the experience of dissociation. The Polish version of the RHS is characterised by good psychometric properties and may be used as an assessing scale for psychotic like experiences in a population. Our results suggest that hallucinatory like experiences are present among healthy subjects and those phenomenon may represent a psychosis phenotype.


Epstein-Barr virus genome level, T-cell clonality and the prognosis of angioimmunoblastic T-cell lymphoma.
Angioimmunoblastic T-cell lymphoma (AILT) is a peripheral T-cell tumor of unknown etiology with variable biological and clinical presentations. Previous clonality studies have shown heterogeneous clonal restrictions of B- and T-cell populations in this tumor. AILT is characterized by the presence of increased numbers of Epstein-Barr virus (EBV) infected cells. The aim of this study was to clarify the correlation between clonality, EBV and prognosis. Frozen material from 59 cases of AILT was used for DNA isolation and gene analysis by Southern blotting. A real-time polymerase chain reaction was used to quantify the amount of EBV-DNA in the tissue. Survival data were retrieved from clinical records. Clonal T cells were found in 15/50 and clonal B-cells in 2/50 tumors, using Southern blot analysis. Bands of EBV-W were found in 10/50 tumors. Survival rate did not correlate with either T-cell clonality (p=0.84), or presence of EBV-infected cells (p=0.84). The EBV-DNA copy number in EBV-infected tissue did not correlate with disease progression (p=0.87). The survival rate and clinical status according to the international prognostic index (IPI) did not correlate with T-cell clonality status or EBV infection. AILT remains a heterogeneous disease with clinical behavior that varies irrespective of the genomic parameters investigated.


Vitamin B12 transport from food to the body's cells--a sophisticated, multistep pathway.
Vitamin B(12) (B(12); also known as cobalamin) is a cofactor in many metabolic processes; deficiency of this vitamin is associated with megaloblastic anaemia and various neurological disorders. In contrast to many prokaryotes, humans and other mammals are unable to synthesize B(12). Instead, a sophisticated pathway for specific uptake and transport of this molecule has evolved. Failure in the gastrointestinal part of this pathway is the most common cause of nondietary-induced B(12) deficiency disease. However, although less frequent, defects in cellular processing and further downstream steps in the transport pathway are also known culprits of functional B(12) deficiency. Biochemical and genetic approaches have identified novel proteins in the B(12) transport pathway--now known to involve more than 15 gene products--delineating a coherent pathway for B(12) trafficking from food to the body's cells. Some of these gene products are specifically dedicated to B(12) transport, whereas others embrace additional roles, which explains the heterogeneity in the clinical picture of the many genetic disorders causing B(12) deficiency. This Review describes basic and clinical features of this multistep pathway with emphasis on gastrointestinal transport of B(12) and its importance in clinical medicine.


Transfusion-related acute lung injury (TRALI) following autologous stem cell transplant for relapsed acute myeloid leukaemia: a case report and review of the literature.
A fatal case of transfusion-related acute lung injury (TRALI) in a child post-autologous stem cell transplant for relapsed acute myeloid leukaemia is described. The implicated product was a single unit platelet concentrate containing anti-HLA A2 and granulocyte-specific anti-NA1 antibodies. The recipient typed as HLA A2/A2, NA1/NA1. This is the first reported case of TRALI following a transplant procedure for a haematological condition. It is also unusual in that the patient failed to make a full recovery and that two relevant leucocyte antibodies of clear specificity were identified in the donor plasma. The literature relating to the pathophysiology, clinical sequelae and management of TRALI is reviewed.


Training of voluntary torsion.
By means of a visual feedback technique, human subjects were trained to make large conjugate cyclorotary eye movements at will. The range of movement increased with training at a rate of approximately 0.8 degrees per hour of practice, reaching 30 degrees at the end of training. Photographs recorded the ability to make voluntary cyclofixations at any amplitude within the subject's range. Cyclotorsional pursuit was also trained, with ability increasing with greater amounts of fisual feedback. In addition, torsional saccadic tracking was trained, showing a magnitude vs. peak velocity relationship similar to that seen for normal saccades. Control experiments indicate that all of these movements were voluntary, with no significant visual induction. With extended practice, large torsional movements could be made without any visual stimulation. The emergence of voluntary torsion through training demonstrates that the oculomotor system has more plasticity than has generally been assumed, reopening the issue as to whether other movements could also be trained to alleviate the symptoms of strabismus.


[Retroviruses: current classification system].
Based on the various viral properties, the recent Retrovirus classifications are reported. After describing the HIV characteristics with the transactivation capability, the authors include the HIV among the Lentivirinae.


Lewis acid activation of Weiss' reagents ([PhI(Pyr)2]2+) with boranes and isolation of [PhI(4-DMAP)]2.
Abstraction of a pyridine ligand from Weiss' reagent ([PhI(Pyr)2]2+) using BF3-Et2O was found to activate Weiss' reagent towards electrophilic aromatic substitution reactions. The activated species can be isolated when 4-DMAP is used as the pyridine ligand and was determined to be [PhI(4-DMAP)]2+ in solution. The isolated cation was reactive in electrophilic aromatic substitution reactions towards mesitylene, xylene and toluene that Weiss' reagent itself does not react with.


[The use of relaparotomy in emergency surgery].
After operative intervention in 61 of the 5704 patients, as necessity in performance of relaparotomy arose. Mortality after its use was 38%.


Field-dependence/field-independence and labeling of facial affect.
56 high school students were administered the Group Embedded Figures Test and the Pictures of Facial Affect. A low Pearson product-moment correlation of .02 was obtained between the measures. Data indicated that field-dependent and field-independent individuals were not signficantly different in their skills of labeling pictures of facial affect.


Time-Resolved Particle Image Velocimetry Measurements with Wall Shear Stress and Uncertainty Quantification for the FDA Nozzle Model.
We present advanced particle image velocimetry (PIV) processing, post-processing, and uncertainty estimation techniques to support the validation of computational fluid dynamics analyses of medical devices. This work is an extension of a previous FDA-sponsored multi-laboratory study, which used a medical device mimicking geometry referred to as the FDA benchmark nozzle model. Experimental measurements were performed using time-resolved PIV at five overlapping regions of the model for Reynolds numbers in the nozzle throat of 500, 2000, 5000, and 8000. Images included a twofold increase in spatial resolution in comparison to the previous study. Data was processed using ensemble correlation, dynamic range enhancement, and phase correlations to increase signal-to-noise ratios and measurement accuracy, and to resolve flow regions with large velocity ranges and gradients, which is typical of many blood-contacting medical devices. Parameters relevant to device safety, including shear stress at the wall and in bulk flow, were computed using radial basis functions. In addition, in-field spatially resolved pressure distributions, Reynolds stresses, and energy dissipation rates were computed from PIV measurements. Velocity measurement uncertainty was estimated directly from the PIV correlation plane, and uncertainty analysis for wall shear stress at each measurement location was performed using a Monte Carlo model. Local velocity uncertainty varied greatly and depended largely on local conditions such as particle seeding, velocity gradients, and particle displacements. Uncertainty in low velocity regions in the sudden expansion section of the nozzle was greatly reduced by over an order of magnitude when dynamic range enhancement was applied. Wall shear stress uncertainty was dominated by uncertainty contributions from velocity estimations, which were shown to account for 90-99% of the total uncertainty. This study provides advancements in the PIV processing methodologies over the previous work through increased PIV image resolution, use of robust image processing algorithms for near-wall velocity measurements and wall shear stress calculations, and uncertainty analyses for both velocity and wall shear stress measurements. The velocity and shear stress analysis, with spatially distributed uncertainty estimates, highlights the challenges of flow quantification in medical devices and provides potential methods to overcome such challenges.


Analytical Method for Experimental Validation of Computer-Designed Antibody.
In the computational design of antibodies, the interaction analysis between target antigen and antibody is an essential process to obtain feedback for validation and optimization of the design. Kinetic and thermodynamic parameters as well as binding affinity (KD) allow for a more detailed evaluation and understanding of the molecular recognition. In this chapter, we summarize the conventional experimental methods which can calculate KD value (ELISA, FP), analyze a binding activity to actual cells (FCM), and evaluate the kinetic and thermodynamic parameters (ITC, SPR, BLI), including high-throughput analysis and a recently developed experimental technique.


An Unusual Cause of Out-of-Hospital Cardiac Arrest Recorded on a Heartrate Monitor.
Coronary vasospasm is an uncommon, but perhaps under-recognised, cause of cardiac arrest. We present a novel case of an exercise-induced out-of-hospital cardiac arrest due to coronary vasospasm, captured on a heartrate monitor, and discuss the management options for this condition.


Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase with reduced affinity for PP-ribose-P in four related males with gout.
A family is described in which four affected males, spanning two generations, have hyperuricemia and gout accompanied by hematuria but are without severe neurologic involvement. The affected males were found to have markedly reduced levels of erythrocytic hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity; these were 5-12% with hypoxanthine and 0.5-3% with guanine as compared to controls. Erythrocytic adenine phosphoribosyltransferase (APRT) was approximately three-fold elevated in the affected individuals. The residual HGPRT activity in affected males enabled characterization of some of the properties of this mutation. The apparent Michaelis constants (km) for both hypoxanthine and guanine were essentially unchanged, whereas the km for PP-ribose-P was approximately 10-20-fold elevated for all four affected males. The enzyme was more sensitive to product inhibition by IMP and GMP than controls, and exhibited greater thermal lability at 65 degrees C than found with control lysates.


Are there any good experiments that should not be done?
Is there any research that should not be done? Could you think of an experiment and then decide not to do it? These questions get to the heart of the power of modern genetics to mix up and alter genes.


Kinetics and metabolism of carbamazepine during combined antiepileptic drug therapy.
The kinetics of carbamazepine using 15N-carbamazepine were investigated in epileptic patients during combined anticonvulsant therapy. The 15N-carbamazepine plasma half-lives ranged from 5.0 to 13.6 hr with a mean of 8.2 hr. These half-lives are appreciably shorter than reported during chronic carbamazepine monotherapy. Predicted steady-state plasma levels and observed plasma levels of carbamazepine were in excellent agreement. Between 32% and 61% of the dose administered is excreted in the urine as carbamazepine-trans-diol, 5.2% to 8.8% as 9-hydroxymethyl-10-carbamoyl acridane, 1% to 1.4% as 10,-11-carbamazepine epoxide, and 0.5% as carbamazepine. The data indicate that it is the epoxide-diol pathway which is induced during long-term treatment. Concomitant therapy with primidone, phenytoin, phenobarbital, ethosuximide, or methsuximide further induces carbamazepine metabolism.