Catheter ablation of ventricular arrhythmias in left ventricular noncompaction cardiomyopathy.
There are limited data on ventricular arrhythmias (VAs) associated with left ventricular noncompaction (LVNC) cardiomyopathy. This study aims to analyze the clinical and electrocardiographic characteristics of VAs in a group of patients with LVNC. Forty-two nonrelated patients with LVNC and VAs were included that were evaluated at the Inherited Cardiac Disease Unit of the University Hospital Virgen Arrixaca (Murcia-Spain) (ERN Guard-Heart Centre, European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart). Thirteen patients (30.9%) had isolated LVNC, 27 (64.3%) had LVNC associated with dilated cardiomyopathy, and 2 (4.8%) had LVNC associated with hypertrophic cardiomyopathy. Among isolated LVNC individuals, 9 (69.2%) had premature ventricular complexes (PVCs)/nonsustained ventricular tachycardias (VTs), and 4 (30.8%) VTs (1 VT degenerating in ventricular fibrillation). In the dilated cardiomyopathy group, 11 (40.7%) patients had PVCs, 14 (51.9%) VTs, and 2 (7.4%) ventricular fibrillation. In the hypertrophic cardiomyopathy group, one patient had PVCs and the other VTs. Endocardial mapping and ablation were performed in 19 patients (45.2%): 7 ventricular outflow tracts (4 right ventricular outflow tract, 1 left coronary cusp, and 2 right coronary cusp), 2 in the left ventricular summit, 5 related to Purkinje potentials at the mid inferoseptal area, and 5 associated with endocardial scar localized in the basal anterolateral and inferolateral segments. Epicardial ablation was performed in 3 cases. The substrate of VAs in LVNC cardiomyopathy is heterogeneous, with origin in ventricular outflow tracts, Purkinje system related, and resembling scar patterns in nonischemic cardiomyopathy.


Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery.
We previously described chimeric recombinant adeno-associated virus (rAAV) vectors 2/4 and 2/5 as the most efficient vectors in rat retina. We now characterize these two vectors carrying the CMV.gfp genome following subretinal injection in the Wistar rat, beagle dog, and cynomolgus macaque. Both serotypes displayed stable GFP expression for the duration of the experiment (6 months) in all three animal models. Similar to the AAV-2 serotype, AAV-2/5 transduced both RPE and photoreceptor cells, with higher level of transduction in photoreceptors, whereas rAAV-2/4 transduction was unambiguously restricted to RPE cells. This unique specificity found conserved among all three species makes AAV-2/4-derived vectors attractive for retinal diseases originating in RPE such as Leber congenital amaurosis (RPE65) or retinitis pigmentosa due to a mutated mertk gene. To provide further important preclinical data, vector shedding was monitored by PCR in various biological fluids for 2 months post-rAAV administration. Following rAAV-2/4 and -5 subretinal delivery in dogs (n = 6) and in nonhuman primates (n = 2), vector genome was found in lacrymal and nasal fluids for up to 3-4 days and in the serum for up to 15-20 days. Overall, these findings will have a practical impact on the development of future gene therapy trials of retinal diseases.


Wolbachia in Aedes koreicus: Rare Detections and Possible Implications.
The emerging distribution of new alien mosquito species was recently described in Europe. In addition to the invasion of Aedes albopictus, several studies have focused on monitoring and controlling other invasive Aedes species, as Aedes koreicus and Aedes japonicus. Considering the increasing development of insecticide resistance in Aedes mosquitoes, new control strategies, including the use of bacterial host symbionts, are proposed. However, little is known about the bacterial communities associated with these species, thus the identification of possible candidates for Symbiotic Control is currently limited. The characterization of the natural microbiota of field-collected Ae. koreicus mosquitoes from North-East Italy through PCR screening, identified native infections of Wolbachia in this species that is also largely colonized by Asaia bacteria. Since Asaia and Wolbachia are proposed as novel tools for Symbiotic Control, our study supports their use for innovative control strategies against new invasive species. Although the presence of Asaia was previously characterized in Ae. koreicus, our study characterized this Wolbachia strain, also inferring its phylogenetic position. The co-presence of Wolbachia and Asaia may provide additional information about microbial competition in mosquito, and to select suitable phenotypes for the suppression of pathogen transmission and for the manipulation of host reproduction in Ae. koreicus.


Split-half and test-retest Hand Test reliabilities for pathological samples.
Computed split-half and test-retest reliabilities for some major Hand Test scoring categories for a group of 100 Ss of mixed psychopathology. All correlations were significant; the rs ranged from "modest" to "high.' Withdrawal, the most serious of all indices of psychopathology, showed the most consistency across both split-half and test-retest formats. Results were interpreted as lending credence to Hand Test rationale. Reliabilities appear high enough to justify the clinical use of the technique.


Longevity, stability and DNA repair.
The functional capacity of a cell, tissue, organ, or organism is dependent upon its ability to maintain the stability of its unit components. The higher the differentiated state of the system, the greater the amount of stability required to maintain that state as a function of time. Stability can be achieved via either redundancy or repair. Redundancy while easily achievable in biological systems is both costly and limited by thermodynamic considerations. Repair, in its general sense, has no such limitations. Repair at the cellular and macromolecular level is multiple in its forms and varies as a function of species, tissue, and stage of the cell cycle. The repair of DNA damage is a dynamic process with many components and subcomponents, each interacting with one another in order to achieve a balance between individual stability and evolutionary diversity. Thus, between internal and external factors which damage DNA and the subsequent expression of alterations in the functional stability of DNA lie the multi-functional pathways which attempt to maintain DNA fidelity. A strong correlation between ulta-violet light induced excision or pre-replication repair, as measured by autoradiogrphy and maximum species lifespan has been reported within different strains of the same species, between related species (e.g. Mus musculus and Peromyscus leucopus), between five orders of mammals, and most recently within members of the primate family. As has been demonstrated by the authors and others, differences in excision repair between species and tissues may relate to the turning off of portions of the repair processes during embryogenesis. Regardless of why such correlations exist or the nature of their mechanisms, it is naive to either assert or deny a causal role for DNA repair in longevity assurance systems. For example, while species-related differences in DNA repair may reflect the turning off of such repair processes during fetal development this does not mean that rates of accumulation of DNA damage are not altered by such changes. Indeed, such a phenomena might well explain the rapid evolution of lifespan within the primates without a concurrent input of new genes.


The Dark Side of Estrogen Stops Translation to Induce Apoptosis.
The role of hormones in triggering cell death has been controversial. In this issue of Molecular Cell, Li et al. (2019) have defined a molecular pathway where an unexpected estrogen receptor, phosphodiesterase 3A, allows its partner Schlafen-12 to inhibit survival pathways, ultimately leading to apoptosis.


Identification and characterization of a novel glutaminase inhibitor.
In humans, there are two forms of glutaminase (GLS), designated GLS1 and GLS2. These enzymes catalyse the conversion of glutamine to glutamate. GLS1 exists as two isozymes: kidney glutaminase (KGA) and glutaminase C (GAC). Several GLS inhibitors have been identified, of which DON (6-diazo-5-oxonorleucine), BPTES (bis-2-(5-phenylacetamido-1, 3, 4-thiadiazol-2-yl) ethyl sulphide), 968 (5-(3-Bromo-4-(dimethylamino)phenyl)-2,2-dimethyl-2,3,5,6-tetrahydrobenzo[a]phenanthridin-4(1H)-one) and CB839 (Telaglenastat) are the most widely used. However, these inhibitors have variable efficacy, specificity and bioavailability in research and clinical settings, implying the need for novel and improved GLS inhibitors. Based on this need, a diverse library of 28,000 compounds from Enamine was screened for inhibition of recombinant, purified GAC. From this library, one inhibitor designated compound 19 (C19) was identified with kinetic features revealing allosteric inhibition of GAC in the µm range. Moreover, C19 inhibits anti-CD3/CD28-induced CD4+ T-cell proliferation and cytokine production with similar or greater potency as compared to BPTES. Taken together, our data suggest that C19 has the potential to modulate GLS1 activity and alter metabolic activity of T cells.


Frontal fibrosing alopecia and personal care product use: a systematic review and meta-analysis.
Frontal fibrosing alopecia (FFA) is a cicatricial alopecia affecting the frontotemporal hairline. Given that this scarring, immune-mediated follicular destruction most commonly affects postmenopausal Caucasian women, researchers have postulated that there are hormonal and genetic components; however, the etiology of FFA is still unknown. Recently, dermatologists have reported cases of FFA as being potentially caused by cosmetic products, such as sunscreen and shampoo. Therefore, this systematic review and meta-analysis intend to be the first to analyze the relationship between FFA and cosmetic/personal care products and treatments, including sunscreen, moisturizer, foundation, shampoo, conditioner, hair mousse, hair gel, hair dye, hair straightening/rebonding, chemical/laser facial resurfacing, aftershave, and facial cleanser. The Cochrane, PubMed, EMBASE, and Medline (Ovid) databases were searched for the relevant studies from the date of inception to August 2022. Case-control, cross-sectional, and cohort studies examining the effects of cosmetic/personal care product use on FFA, available in English full-text, were included. Analyses were performed using Review Manager, version 5.4. Results were reported as an odds ratio (OR) with a 95% confidence interval (CI); p values < 0.05 were considered significant. Nine studies were included in our quantitative analyses, totaling 1,248 FFA patients and 1,459 controls. There were significant positive associations found for FFA and sunscreen (OR 3.02, 95% CI 1.67-5.47; p = 0.0003) and facial moisturizer (OR 2.20, 95% CI 1.51-3.20; p < 0.0001) use. Gender sub-analyses demonstrated a positive association for FFA and facial moisturizer in men (OR 5.07, 95% CI 1.40-18.32; p = 0.01), but not in women (OR 1.58, 95% CI 0.83-2.98; p = 0.16). Both gender sub-analyses were significantly positive for the association with facial sunscreen (Male OR 4.61, 95% CI 1.54-13.78, p = 0.006; Female OR 2.74, 95% CI 1.32-5.70, p = 0.007). There was no association found for a facial cleanser (OR 1.14, 95% CI 0.33-1.52; p = 0.51), foundation (OR 1.13, 95% CI 0.83-1.55; p = 0.21), shampoo (OR 0.49, 95% CI 0.22-1.10; p = 0.08), hair conditioner (OR 0.81, 95% CI 0.52-1.26; p = 0.35), hair mousse (OR 1.37, 95% CI 0.75-2.51; p = 0.31), and hair gel (OR 0.90, 95% CI 0.48-1.69; p = 0.74), hair dye (OR 1.07, 95% CI 0.69-1.64; p = 0.77), hair straightening/rebonding (OR 0.88, 95% CI 0.08-9.32; p = 0.92), hair perming (OR 1.41, 95% CI 0.89-2.23; p = 0.14), facial toner (OR 0.51, 95% CI 0.12-2.21; p = 0.37), or aftershave (OR 1.64, 95% CI 0.28-9.49; p = 0.58). This meta-analysis strongly suggests that leave-on facial products, facial sunscreen and moisturizer, are associated with FFA. While the association with facial moisturizer did not persist when stratifying for female populations, gender sub-analyses remained significant for a facial sunscreen. There was no significant relationship found with hair products or treatments. These findings suggest a potential environmental etiology in the development of FFA, particularly UV-protecting chemicals.


Zinc-aggravated M1 microglia regulate astrocytic engulfment via P2×7 receptors.
Glial cells such as astrocytes and microglia play an important role in the central nervous system via communication between these glial cells. Activated microglia can exhibit either the inflammatory M1 phenotype or the anti-inflammatory M2 phenotype, which influences astrocytic neuroprotective functions, including engulfment of cell debris. Recently, extracellular zinc has been shown to promote the inflammatory M1 phenotype in microglia through intracellular zinc accumulation and reactive oxygen species (ROS) generation. Here, we investigated whether the zinc-enhanced inflammatory M1 phenotype of microglia affects the astrocytic engulfing activity. Engulfing activity was assessed in astrocytes treated with microglial-conditioned medium (MCM) from lipopolysaccharide (LPS)-activated or from ZnCl2-pretreated LPS-activated M1 microglia. The effect of zinc on microglia phenotype was also validated using the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and the ROS scavenger Trolox. Although treatment of astrocytes with LPS showed no significant effect on the engulfing activity, MCM from LPS-induced M1 microglia increased the beads uptake by astrocytes. This increased uptake activity was suppressed when MCM from LPS-induced M1 microglia pretreated with ZnCl2 was applied to astrocytes, which was further abolished by the intracellular zinc chelator TPEN and the ROS scavenger Trolox. In addition, expression of P2×7 receptors (P2×7R) was increased in astrocytes treated with MCM derived from M1 microglia but not in the M1 microglia pretreated with ZnCl2. These findings suggest that zinc pre-treatment abolishes the ability of LPS-induced M1 microglia to increase the engulfing activity in astrocytes via alteration of astrocytic P2×7R.


Bioactive sulfoximines: syntheses and properties of Vioxx analogs.
The syntheses and biological profiles of sulfoximine-based Vioxx analogs 2 are described. Interesting data have been obtained for 2a, which shows a selective COX-2 inhibition (albeit not as strong as Vioxx itself) exhibiting reduced hERG activity compare to the parent sulfone Vioxx (1).


Stöber method and its nuances over the years.
Some characteristics of silica-based materials, such as the control/adjustment of their physical and chemical properties, compatibility, and friendly-use synthesis methods, have held the attention of several scientific groups over the years. This condition of prominence becomes even more evident when we seek these characteristics at the micro- and/or nanoscale. Among existing methods to obtain these micro/nanomaterials, the Stöber method is the focus of this review. This method is known to enable the production of silica micro- or nanoparticles from reagents of medium-easy manipulation under mild conditions using equipment that is common in most laboratories. However, this method has many nuances that must be considered to guarantee accurate results, either in size or distribution, and to ensure result reproducibility. Thus, in this review, we discuss the effects of the primary components used in the synthesis of these materials (i.e., TEOS, ammonia, and water), as well as those of other reaction conditions, such as solvent, temperature, and ionic strength. Therefore, we discuss studies involving the synthesis and characterization of micro- and nanoparticles over the years to establish discussions between their experimental observations and proposed models. This review provides experimental observations about the synthesis of these materials, as well as discussions according to complementary and/or contradictory evidence found over the years. This review seeks to help those who intend to work with this method and provide certain key points that, in our experience, can be important to obtain desired results.


Immunocytochemical localization of BGP in human bones in various developmental stages and pathological conditions.
Bone gamma-carboxyglutamic acid containing protein (BGP) was isolated from human bone and anti-BGP antibody was produced in rabbits. Localization of BGP was investigated immunocytochemically by light and electron microscopy in human bones in various developmental stages and pathological conditions. In the bones of a 12 week fetus, osteoblasts stained strongly in areas of bone formation. However in bones of late fetal stages and in newborns and adults, BGP was localized predominantly in the osteoid and bone matrix in the ossifying front. Osteoblasts and osteocytes also stained positive, but less dominantly than in the early fetus. Electron microscopy showed that BGP was localized in the ER and Golgi cisternae of osteoblasts and osteocytes, and the collagen fibers of the osteoid and bone matrix. The intensity and distribution of staining were not significantly different in osteoporosis and osteoarthritis. These observations indicate that BGP is synthesized by osteoblasts most actively in early fetal life and is then deposited on collagen fibers of the osteoid and bone matrix.


"Scanxiety" and a sense of control: the perspective of lung cancer survivors and their caregivers on follow-up - a qualitative study.
Lung cancer survivors often suffer from physical, emotional and social long-term effects of disease and treatment. Caregivers are also affected by the cancer diagnosis throughout the course of the disease and are frequently burdened by high levels of psychosocial stress. However, little is known about how follow-up care after the completed treatment phase can help to improve long-term quality of life. In the context of patient-centred cancer care, considering the survivors' and caregivers' perspectives is an important step toward improving care structures. We therefore explored how lung cancer survivors and their caregivers experience follow-up examinations and their possible psychosocial effects on everyday life in order to shed light on what support is helpful for improving their quality of life. 25 survivors after curative lung cancer treatment and 17 caregivers underwent a face-to-face semi-structured, audio-recorded interview that was analysed using qualitative content analysis. Especially burdened cancer survivors and caregivers described recurring anxiety before a follow-up appointment influencing their everyday life. At the same time, follow-up care also provided reassurance of still being healthy and helped regain a sense of security and control until the following scan. Despite possible long-term consequences in everyday life, the interviewees reported that the survivors´ psychosocial needs were not explicitly assessed or discussed. Nevertheless, the interviewees indicated that conversations with the physician were important for the success of "good" follow-up care. Anxiety surrounding follow-up scans, also known as "scanxiety", is a common problem. In this study, we expanded on previous findings and found a positive aspect of scans, namely regaining a sense of security and control, which can strengthen the psychological well-being of the survivors and their families. To optimize follow-up care and improve the quality of life of lung cancer survivors and caregivers, strategies to integrate psychosocial care, like the introduction of survivorship care plans or increased use of patient-reported outcomes, should be explored in the future.


DNAfusion: an R/Bioconductor package for increased sensitivity of detecting gene fusions in liquid biopsies.
EML4-ALK gene fusions are oncogenic drivers in non-small cell lung cancer (NSCLC), and liquid biopsies containing EML4-ALK fragments can be used to study tumor dynamics using next-generation sequencing (NGS). However, the sensitivity of EML4-ALK detection varies between pipelines and analysis tools. We developed an R/Bioconductor package, DNAfusion, which can be applied to BAM files generated by commercially available NGS pipelines, such as AVENIO. Forty-eight blood samples from a training cohort consisting of 41 stage IV EML4-ALK-positive NSCLC patients and seven healthy controls were used to develop DNAfusion. DNAfusion detected EML4-ALK in significantly more samples (sensitivity = 61.0%) compared to AVENIO (sensitivity = 36.6%). The newly identified EML4-ALK-positive patients were verified using droplet digital PCR. DNAfusion was subsequently validated in a blinded validation cohort comprising 24 EML4-ALK-positive and 24 EML4-ALK-negative stage IV NSCLC patients. DNAfusion detected significantly more EML4-ALK individuals in the validation cohort (sensitivity = 62.5%) compared to AVENIO (sensitivity = 29.2%). DNAfusion demonstrated a specificity of 100% in both the training and validation cohorts. Here we present DNAfusion, which increases the sensitivity of EML4-ALK detection in liquid biopsies and can be implemented downstream of commercially available NGS pipelines. The simplistic method of operating the R package makes it easy to implement in the clinical setting, enabling wider expansion of NGS-based diagnostics.


Cesium uptake and translocation from tea cutting roots (Camellia sinensis L.).
To estimate the uptake of radiocesium (137Cs) by tea plant roots, 1-year-old rooted tea cuttings (Camellia sinensis L. cv. Yabukita) at the time of bud opening were cultivated hydroponically for 27 days in pots containing nutrient solutions with or without 137CsCl (600 Bq mL-1). Total 137Cs radioactivity of whole tea plants were 6.1 kBq g-1 dry weight. The plant/solution 137Cs transfer factors of different tissues were in the range of 2.6 (in mature leaves) to 28.2 mL g-1 dry weight (in roots), which were lower than those reported in wheat and spinach. In total, 69% of 137Cs remained in roots and 31% was transported from roots to shoots. The results indicated that 137Cs was preferentially translocated to new shoots, which are used for manufacturing tea, over mature leaves.


Pyrolysis synergy of municipal solid waste (MSW): A review.
The synergistic pyrolysis of municipal solid waste (MSW) were recently explored. This review aims to provide an overview on the synergistic pyrolysis studies of MSW, focusing on the synergy occurred during co-pyrolysis of different constituents of MSW. The interactions of intermediates released during pyrolysis can shift end product distributions, accelerate pyrolysis rates, and preferred production of specific compounds, which were categorized into four basic types with discussions. The pyrolysis synergy is proposed to be the key for success of pyrolytic practice of MSW that can handle the waste with maximal resource recovery and minimal carbon emission.


Lung nodule detection and characterization with multislice CT.
The ability to identify and characterize pulmonary nodules has been dramatically increased by the introduction of multislice CT (MSCT) technology. Using high-resolution sections, MSCT allows considerable improvement in assessing nodule morphology, enhancement patterns, and growth. MSCT also has facilitated the development and potential of clinical application of computer-assisted diagnosis.


Maternal exposure to sulfur dioxide and the risk of oral clefts in Liaoning Province, China: a population-based case-control study.
There is limited and equivocal epidemiological evidence relating to the association between maternal sulfur dioxide (SO2) exposure and the risk of oral clefts (OCs) in offspring. We performed a population-based case-control study in Liaoning province to evaluate aforementioned relationship during 3 months before conception, the first trimester of pregnancy, and their single months. The study involved 3086 patients with OCs and 7950 controls. Data relating to SO2 concentration was acquired from air monitoring stations throughout the study period. We used a multivariable logistic regression model to evaluate the association between exposure to SO2 and the risk of OCs during the exposure windows. Maternal SO2 exposure was positively related to OCs during the 3 months before conception (odds ratio = 1.38, 95% confidence interval: 1.15-1.65; P for trend < 0.01). Positive relationships were obtained from the first and second months before conception and the first month of pregnancy. Thus, our research reflects a relationship between SO2 exposure and the risk of OCs. Future studies are now required to verify the association between SO2 exposure and OCs during pregnancy and indicate the most relevant vulnerable exposure time windows.


Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial.
Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer. The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer. Patients were recruited for this open-label, phase 2 randomised trial between March 17, 2003, and May 19, 2006, at a single centre. Eligible patients had clinical stage II-III (> or = T2 and/or > or = N1) newly diagnosed breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, and normal cardiac, renal, and liver function. 120 women were randomly assigned, using allocation concealment, to receive 4 mg zoledronic acid intravenously every 3 weeks (n=60), or no zoledronic acid (n=60), for 1 year concomitant with four cycles of neoadjuvant epirubicin (75 mg/m(2)) plus docetaxel (75 mg/m(2)) and two cycles of adjuvant epirubicin plus docetaxel. The primary endpoint was the number of patients with detectable DTCs at 3 months. Final analysis was done 1 year after the last patient was enrolled. Analyses were done for all patients with available data at 3 months. This study is registered with ClinicalTrials.gov, number NCT00242203. Of the 120 patients initially enrolled, one withdrew after signing consent and one patient's baseline bone marrow was not available. Both of these patients were in the control group. At 3 months, 109 bone-marrow samples were available for analysis. In the zoledronic acid group, bone marrow was not collected from one patient because of disease progression, one patient was taken off study because of severe diarrhoea, and two patients had not consented at the time of surgery. In the control group, bone marrow was not collected from two patients because of disease progression, one patient withdrew consent, and three patients were not consented at the time of surgery. At baseline, DTCs were detected in 26 of 60 patients in the zoledronic acid group and 28 of 58 patients in the control group. At 3 months, 17 of 56 patients receiving zoledronic acid versus 25 of 53 patients who did not receive zoledronic acid had detectable DTCs (p=0.054). The most common grade 3-4 toxicities were infection (five of 60 patients in the zoledronic acid group and six of 59 in the control group) and thrombosis (five of 60 in the zoledronic acid and two of 59 in the control group). There was one documented case of osteonecrosis in the zoledronic acid group. Zoledronic acid administered with chemotherapy resulted in a decreased proportion of patients with DTCs detected in the bone marrow at the time of surgery. Our study supports the hypothesis that the antimetastatic effects of zoledronic acid may be through effects on DTCs. Novartis Pharmaceuticals and Pfizer Inc.


Low-dose desoxycorticosterone pivalate treatment of hypoadrenocorticism in dogs: A randomized controlled clinical trial.
Desoxycorticosterone pivalate (DOCP) is a commonly used mineralocorticoid replacement for dogs with primary hypoadrenocorticism (HA), but manufacturer-recommended dosing protocols can be cost-prohibitive. Recent reports also have raised concerns that label dose protocols could be excessive. To investigate the relative efficacy and adverse effects of 2 DOCP dosages in dogs with primary glucocorticoid and mineralocorticoid deficient HA. Thirty-seven dogs, including 19 test population dogs and 18 controls. Randomized controlled double-blinded clinical trial. Dogs with newly diagnosed primary HA were assigned to standard (2.2 mg/kg q30d, control population) or low-dose (1.1 mg/kg q30d, test population) DOCP treatment. Clinical and laboratory variables were assessed 10 to 14 days and approximately 30 days after each DOCP treatment for 90 days. Mean serum sodium to potassium ratios at reevaluations were ≥32 in both populations throughout the study. No dog developed electrolyte abnormalities warranting medical treatment, although hypokalemia occurred on at least 1 occasion in 9 controls and 6 test population dogs. Urine specific gravities (median, interquartile range) were lower in control dogs (1.022, 1.016-1.029) as compared to test population dogs (1.033, 1.023-1.039; P = .006). Plasma renin activity was overly suppressed on 84 of 104 (80.8%) assessments in control dogs whereas increased renin activity occurred on 23 of 112 (20.5%) assessments in test population dogs. Low-dose DOCP protocols appear to be safe and effective for treatment of HA in most dogs. Standard-dose protocols are more likely to result in biochemical evidence of overtreatment.


Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein.
Oxidative modification of glucose-6-phosphate dehydrogenase (Glu-6-PDH), as observed for other proteins, increases the susceptibility of the protein to degradation by the multicatalytic proteinase/proteasome (MCP). Oxidized Glu-6-PDH is, however, more prone to cross-linking reactions by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE), processes which render the protein resistant to proteolysis. In addition, HNE cross-linked protein inhibits the degradation of oxidatively modified glutamine synthetase by the MCP. In contrast to oxidized Glu-6-PDH, which inhibits the proteolysis of GS in a competitive manner, HNE cross-linked protein acts as a noncompetitive inhibitor. As judged by binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, a common structural feature of both macromolecular substrates and inhibitors of the MCP is an increased accessibility of hydrophobic regions on the protein.


The effect of exposure to hypoxia on superoxide formation by alveolar macrophages is indirect.
To elucidate the role of alveolar macrophages (AM) in the pathogenesis of hypoxic pulmonary hypertension (HPH), we tested the effects of sustained hypoxia on AM polarization and on the formation of superoxide by AM in vivo and in vitro. Rat AM were obtained by bronchoalveolar lavage. 4-day exposure to hypoxia (10% O2) was carried out in vivo (rats in isobaric hypoxic chamber, controls kept in air) or in vitro (control AM in 21% O2 and 5% CO2). Superoxide production was measured by luminol-orthovanadate chemiluminescence, AM polarization was detected immunocytochemically. To ascertain the effect of substances contained in the alveolar environment, we cultivated cells also in the presence of non-cellular components of the bronchoalveolar lavage fluid (BALF) either from controls or from rats exposed to 4 days of hypoxia. In vivo, but not in vitro, hypoxia increased AM superoxide production. Both types of hypoxia polarized AM into M2 (pro-proliferative) type. While the presence of control BALF attenuated superoxide production in AM cultivated in normoxia, BALF from the hypoxia-exposed rats had no effect. In AM cultivated in hypoxia, superoxide production was not altered by control BALF and elevated by BALF obtained from hypoxic rats. Hypoxia does not influence superoxide production by AM directly but rather by modulating their milieu and their sensitivity to external influences.


Complement Regulation and Immune Evasion by Hepatitis C Virus.
A prominent role for complement has been identified in the linkage of innate and adaptive immunity. The liver is the main source of complement and hepatocytes are the primary sites for synthesis of complement components in vivo. We have discovered that hepatitis C virus (HCV) impairs C4 and C3 synthesis. Liver damage may diminish capacity of complement synthesis in patients. However, we observed that the changes in measured complement components in chronically HCV infected patients do not correlate with liver fibrosis or rheumatoid factor present in the blood, serum albumin, or alkaline phosphatase levels. Complement component C3 is of critical importance in B cell activation and T cell-dependent antibody responses. C3 activity is required for optimal expansion of CD8+T cells during a systemic viral infection. Deficiencies in complement may predispose patients to infections via ineffective opsonization, and defects in lytic activity via membrane attack complex. Interestingly, C9 is significantly reduced at the mRNA level in chronically HCV infected liver biopsy specimens, while many hepatocyte derived complement components (C6, C8, Factor B, MASP1, and MBL) and unrelated genes remain mostly unaffected. This implies an HCV specific effect, not a global effect from liver disease.


Tissular cycli AMP levels after treatments with prostaglandins.
In this study both prostaglandin A1 (PGA1) and prostaglandin F2alpha (PGF2alpha) have been shown to be effective long-lasting stimulators of the cyclic AMP (cAMP) synthesis in the liver, intestinal mucosa and brain, whereas prostaglandin E1 (PGE1) was found to have a similar effect on the cerebral cAMP synthesis and a dissimilar effect (decrease) on the hepatic one. A lack of sensitivity of the intestinal mucosa cAMP to PGE1 was also observed.


Self-healing of surface defects on Zn electrode for stable aqueous zinc-ion batteries via manipulating the electrode/electrolyte interphases.
The reversibility and stability of aqueous zinc-ion batteries are largely limited by inevitable parasitic reactions at the interface and uncontrollable dendrite growth. Inspired by self-healing smart electronic materials, we propose a confinement strategy with gelatin, an amphiphilic macromolecule, as additive to regulate the deposition behavior of Zn ions and utilize the dendrites to fill the surface defects formed by inevitable interfacial parasitic reactions. Absorbed gelatin molecules impede H2O reaching Zn electrode surface to enhance the anticorrosion behavior and adjust the local pH value, which is a "smart" way to stabilize the electrode/electrolyte interphase. Additionally, the confined effect of absorbed gelatin molecules on Zn2+ and "electrostatic shield" formed from positive charged -CN3H5+ suppress 2D diffusion and accumulation of Zn2+, guiding Zn continuously depositing inside the defect during electrochemical cycling, then self-healing of electrode surface defects is achieved. Under the synergetic effects of these merits, Zn electrode demonstrates almost unchangeable surface after soaking in the electrolyte for 10 days, and stably cycle more than 1100 h at 0.5 mA cm-2 and 1300 h at 3.0 mA cm-2 in symmetric cell. In addition, the full batteries using the base electrolyte with 0.5 and 1.0 g/L gelatin can stably cycle for 3000 cycles.


Sensitivity to chlorpromazine effects on brain function of schizophrenics and normals. A preliminary report.
For the purpose of quantitative demonstration of the sensitivity to chlorpromazine (CPZ) effects on brain functions of schizophrenics and normal subjects, polygraphic recordings of electroencephalogram (EEG) and electrodermal response (EDR) were performed before and 3 h after oral administration of 25 mg of CPZ: percent time waking EEG (per cent W-EEG) and number per minute of EDR were measured during the resting period and the period of calculation. In 10 normal adult subject, both per cent W-EEG and number of EDR showed remarkable decrease after CPZ administration. In 22 schizophrenics, however, per cent W-EEG showed no significant decrease after CPZ administration. Number of EDR in schizophrenics during the period of calculation did not show any significant decrease. The neural mechanism underlying the lower sensitivity to CPZ effects in schizophrenics was discussed.


Cross-species chromatin interactions drive transcriptional rewiring in Epstein-Barr virus-positive gastric adenocarcinoma.
Epstein-Barr virus (EBV) is associated with several human malignancies including 8-10% of gastric cancers (GCs). Genome-wide analysis of 3D chromatin topologies across GC lines, primary tissue and normal gastric samples revealed chromatin domains specific to EBV-positive GC, exhibiting heterochromatin-to-euchromatin transitions and long-range human-viral interactions with non-integrated EBV episomes. EBV infection in vitro suffices to remodel chromatin topology and function at EBV-interacting host genomic loci, converting H3K9me3+ heterochromatin to H3K4me1+/H3K27ac+ bivalency and unleashing latent enhancers to engage and activate nearby GC-related genes (for example TGFBR2 and MZT1). Higher-order epigenotypes of EBV-positive GC thus signify a novel oncogenic paradigm whereby non-integrative viral genomes can directly alter host epigenetic landscapes ('enhancer infestation'), facilitating proto-oncogene activation and tumorigenesis.


Macromolecular fraction (MMF) from 3D ultrashort echo time cones magnetization transfer (3D UTE-Cones-MT) imaging predicts meniscal degeneration and knee osteoarthritis.
Meniscal degeneration is strongly associated with osteoarthritis (OA). We aimed to evaluate a 3D ultrashort-echo-time Cones magnetization transfer (UTE-Cones-MT) sequence for quantification of macromolecular fraction (MMF) and MT ratio (MTR) in menisci of healthy volunteers and patients with different degrees of OA. Patients with mild OA (n = 19; 37-86 years; 10 males) or advanced OA (n = 12; 52-88 years; 4 males) and healthy volunteers (n = 17; 20-49 years; 7 males) were scanned with T2-FSE and UTE-Cones-MT sequences at 3T. Morphological assessment was performed using meniscal whole-organ magnetic resonance imaging score (WORMS). MMF and MTR were calculated for menisci, and correlated with age and meniscal WORMS scores. The diagnostic efficiency was performed by using receiver operating characteristic (ROC) curve and the area under the curve (AUC) analyses. Decreased MMF and MTR were observed in menisci of patients with mild or advanced OA compared with healthy subjects, and in menisci with tears (Grade 2-4) compared with normal menisci (Grade 0). Significant negative correlations were observed between MMF (r = -0.769, P < 0.01), MTR (r = -0.320, P < 0.01), and meniscal WORMS score. There was a mild negative correlation between MMF (r = -0.438, P < 0.01), MTR (r = -0.289, P < 0.01), and age. The AUC values of MMF and MTR in the four horns of meniscus and the posterior horn medial meniscus for differentiating OA patients from healthy volunteers were 0.762 and 0.699, and 0.835 and 0.883, respectively. The 3D UTE-Cones-MT biomarkers of MTR and especially MMF can detect compositional changes in meniscus and differentiate healthy subjects from patients with mild or advanced knee OA.


Clinical significance of hypouricemia in children and adolescents.
Although hyperuricemia is a widely studied condition with well-known effects on the kidneys, hypouricemia is usually considered a biochemical abnormality of no clinical significance despite the fact that it can be a sign or major finding of serious metabolic or genetic diseases affecting kidney health. In this study, we aimed to investigate and emphasize the clinical significance of hypouricemia. Patients were evaluated retrospectively for persistent hypouricemia defined as serum uric acid concentrations of < 2 mg/dL on at least 3 different occasions. According to the blood and urine uric acid (UA) levels, the patients were classified as having hypouricemia due to UA underproduction vs. overexcretion. Demographic, clinical, and genetic characteristics were noted for analysis. Fourteen patients (n = 14; M/F 8/6) with persistent hypouricemia were identified. Hypouricemia due to underproduction was the cause of 42.8% of these cases. All of the patients with a uric acid level of 0 mg/dL (n = 4) had hypouricemia due to underproduction. The median serum uric acid level was 0.85 (0-1.6) mg/dL. Isolated hypouricemia and hypouricemia with metabolic acidosis were equally distributed. Among the patients with hypouricemia due to underproduction, the final diagnoses were xanthine dehydrogenase deficiency (n = 5) and alkaptonuria (n = 1). In the overexcretion group, the final diagnoses were nephropathic cystinosis (n = 6), distal renal tubular acidosis (n = 1), and hereditary renal hypouricemia (n = 1). The diagnostic lag was longer for patients with isolated hypouricemia compared to other patients (p = 0.001). Hypouricemia may reflect underlying genetic or metabolic diseases, early diagnosis of which could help preserve kidney function. A higher resolution version of the Graphical abstract is available as Supplementary information.


Effects of phase I periodontal treatment on gingival crevicular fluid levels of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1.
The aim of this study was to evaluate the effects of phase I periodontal treatment on gingival crevicular fluid (GCF) levels of matrix metalloproteinase (MMP)-3 and tissue inhibitors of metalloproteinase (TIMP)-1. Plaque index, gingival index, pocket depth and clinical attachment loss were recorded and GCF samples were collected from 20 chronic periodontitis (CP) patients and 20 periodontally healthy controls (C) before treatment. CP patients received phase I periodontal treatment and all clinical parameters were recorded and GCF samples were collected once more after treatment. Assays were performed by an enzyme-linked immunosorbent assay. All of the clinical parameters improved significantly after the therapy (p<0.05). Baseline GCF levels of MMP-3 were significantly higher than C and that level was reduced significantly by treatment compared with baseline levels (p<0.05). Baseline GCF levels of TIMP-1 were lower than post-treatment levels and C (p<0.05). GCF levels of TIMP-1 increased significantly by treatment compared with baseline levels (p<0.05). This study shows that the clinical improvements after phase I periodontal therapy are accompanied by reduction in MMP-3 and increasing in TIMP-1 GCF levels.


Carbamazepine in difficult to control epileptic out-patients.
Twenty-three difficult to control patients with 1 or more seizures per week despite diphenylhydantoin (DPH), phenobarbital and/or primidone in near and toxic doses and blood levels were entered in the study. 3 had grand mal. 8 psychomotor seizures and 12 had both. During a 6 1/2 month study period the patient received active drug and placebo for 3 months each; randomized, double-blind. The dose was to be increased within 4 weeks up to 6 capsules per day equal to 1,200 mg of carbamazepine (C), while the doses or previously taken (basis) anticonvulsants were to remain unchanged. Hematopoetic system and heptic functions were monitored. Complete seizure control attributable to C was not achieved in any, but up to 50% improvement occurred in 12 patients. Questionable improvement was thought to take place in 3 patients, no change occurred in 7, and psychomotor seizures became more frequent in 1 patient. A clear-cut psychotropic effect was not observed. Adverse effects attributable to C were a decline of WBC below 4,000 with relative neutropenia in 3 patients followed by at return to the previous after discontinuation of C. Nystagmus and unsteadiness were seen in about half of the patients, and some headache and drowsiness occurred in one quarter. The highest C blood level was 11.8 mug/ml, the lowest 3.8 mug/ml (average 5.6 mug/ml) during 1,200 mg intake. It seemed, generally, that intoxication occurred with lower blood levels of carbamazepine in those patients whose basis anticonvulsant blood levels were highest.


COVID-19 in the Clinic: Aerosol Containment Mask for Endoscopic Otolaryngologic Clinic Procedures.
To create an aerosol containment mask (ACM) that contains aerosols during common otolaryngologic endoscopic procedures while protecting patients from environmental aerosols. Bench testing. Mannequin testing. The mask was designed in SolidWorks and 3-dimensional printed. Mannequins were fitted with a nebulizer to generate aerosols. Commercial particle counters were used to measure mask performance. The ACM has 2 ports on either side for instruments and endoscopes, a port for a filter, and a port that can evacuate aerosols contained within the mask via a standard suction pump. The mask contained aerosols on a mannequin with and without facial hair when the suction was set to 18.5 L/min. Other types of masks demonstrated substantial aerosol leakage under similar conditions. In a subsequent experiment, the ACM contained aerosols generated by a nebulizer up to the saturation of the particle detector without measurable leakage with or without suction. The ACM will accommodate rigid and flexible endoscopes plus instruments and prevent leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. 2.


Predicting residential ozone deficits from nearby traffic.
Oxides of nitrogen in fresh traffic exhaust are known to scavenge ambient ozone. However, there has only been little study of local variation in ozone resulting from variation in vehicular traffic patterns within communities. Homes of 78 children were selected from a sample of participants in 3 communities in the southern California Children's Health Study. Twenty-four hour ozone measurements were made simultaneously at a home and at a community central site monitor on two occasions between February and November 1994. Homes were geo-coded, and local residential nitrogen oxides (NOx) above regional background due to nearby traffic at each participant's home were estimated using a line source dispersion model. Measured home ozone declined in a predictable manner as modeled residential NOx increased. NOx modeled from local traffic near homes accounted for variation in ozone concentrations of as much as 17 parts per billion. We conclude that residential ozone concentrations may be over- or underestimated by measurements at a community monitor, depending on the variation in local traffic in the community. These findings may have implications for studies of health effects of traffic-related pollutants.


Evaluation of the anatomical factors affecting the success of retrograde intrarenal surgery for isolated lower pole kidney stones.
Studies which examine the factors affecting success rate in kidney stones located in the lower pole as well as the effects of infundibulopelvic angle (IPA) and infundibular length (IL) have been conducted with a small number of patients. We aimed to evaluate the cut-off points of IPA and IL parameters that effect the success of retrograde intrarenal surgery (RIRS) for isolated lower pole kidney stones. This retrospective study includes 168 patients who underwent primary RIRS due to isolated lower pole kidney stones in our clinic between January 2013 and May 2020. Pre-operative demographic data, medical history, physical examination, surgery duration as well as the post-operative hospitalization time of patients specifics were obtained. According to pre-operative computed tomography (CT), stone size, stone burden, stone density, number of stones (single and multiple), stone laterality, congenital kidney abnormality, the presence of solitary kidney, parameters of IPA and IL were measured and both included in the study. All patients were divided into two groups as the successful group and the unsuccessful group according to their post-operative success. These two groups were compared in terms of pre and post-operative data. Stone burden, IPA < 42.65°, and IL > 27.5 mm were specified as the independent risk factors for success of RIRS procedure. The patients for whom RIRS procedure is planned for lower pole kidney stones, stone burden, IPA, and IL should be taken into consideration to be able to predict success and it should be kept in mind that additional treatment may be required.


Safety and efficacy of target-controlled infusion versus intermittent bolus administration of propofol for sedation in colonoscopy: a randomized controlled trial.
Our objective was to compare the safety and efficacy of Target-Controlled Infusion (TCI) versus intermittent bolus of propofol for colonoscopy sedation. We conducted a randomized (1:1), single-blind, parallel-group superiority trial with fifty ASA I or II patients, both sexes, aged 18 to 65 years, Body Mass Index ≤ 30 kg.m-2, undergoing colonoscopy, allocated to receive propofol by TCI (effect-site, 2 μg.mL-1 plus 0.5 μg.mL-1 until unconsciousness and as necessary for agitation) or intermittent bolus (1 mg.kg-1 plus 0.5 mg.kg-1 every 5 minutes or as above). The primary safety outcome was the need for airway maneuvers and the primary efficacy outcome was the need for interventions to adjust the level of sedation. Secondary outcomes included incidence of agitation, propofol dose, and time to recovery. The median (IQR) number of airway maneuvers and interventions needed to adjust sedation was 0 (0‒0) vs. 0 (0‒0) (p = 0.239) and 1 (0‒1) vs. 3 (1‒4) (p < 0.001) in the TCI and control groups, respectively. Agitation was more common in the intermittent bolus group ‒ 2 (0‒2) vs. 1 (0‒1), p < 0.001. The mean ± SD time to recovery was 4.9 ± 1.4 minutes in the TCI group vs. 2.3 ± 1.6 minutes in the control group (p < 0.001). The total propofol dose was higher in the TCI group (234 ± 46 µg.kg-1.min-1 vs. 195 ± 44 µg.kg-1.min-1 (p = 0.040)). During colonoscopy, TCI is as safe as intermittent bolus of propofol while reducing the incidence of agitation and the need for dose adjustments. However, intermittent bolus administration was associated with lower total propofol dose and earlier recovery.


Approach to the management of portal hypertensive gastropathy and gastric antral vascular ectasia.
Gastric antral vascular ectasia (GAVE) and portal hypertensive gastropathy (PHG) are important causes of chronic gastrointestinal bleeding. These gastric mucosal lesions are mostly diagnosed on upper endoscopy and can be distinguished based on their appearance or location in the stomach. In some situations, especially in patients with liver cirrhosis and portal hypertension, a diffuse pattern and involvement of gastric mucosa are seen with both GAVE and severe PHG. The diagnosis in such cases is hard to determine on visual inspection, and thus, biopsy and histologic evaluation can be used to help differentiate GAVE from PHG.


Photoinactivation of microorganisms with sub-micromolar concentrations of imidazolium metallophthalocyanine salts.
The increasingly limited therapeutic options for the treatment of infections caused by multi-resistant Gram-negative bacteria due to the alarming increase in bacteria resistance, renewed interest in photodynamic inactivation (PDI) of bacteria. We address PDI of multi-resistant bacteria with a new family of cationic tetra-imidazolyl phthalocyanines bearing a diversity of cationizing alkylic chain sizes, degrees of cationization and coordinating metals. The antimicrobial activities of the phthalocyanines under white light against Gram-positive and Gram-negative bacteria have remarkable differences in efficacy. We relate their spectroscopic and photophysical properties with the generation of reactive oxygen species (ROS), biological performance and structural features. We show that sub-micromolar concentrations of a Zn(II) tetra-ethyl cationic phthalocyanine reduce colonies of Gram-negative bacteria (E. coli, P. aeruginosa) and C. albicans by 7 log units while leaving mammalian cells unharmed. This is a new lead to address hard-to-treat localized infections.


Wearable electroencephalography and multi-modal mental state classification: A systematic literature review.
Wearable multi-modal time-series classification applications outperform their best uni-modal counterparts and hold great promise. A modality that directly measures electrical correlates from the brain is electroencephalography. Due to varying noise sources, different key brain regions, key frequency bands, and signal characteristics like non-stationarity, techniques for data pre-processing and classification algorithms are task-dependent. Here, a systematic literature review on mental state classification for wearable electroencephalography is presented. Four search terms in different combinations were used for an in-title search. The search was executed on the 29th of June 2022, across Google Scholar, PubMed, IEEEXplore, and ScienceDirect. 76 most relevant publications were set into context as the current state-of-the-art in mental state time-series classification. Pre-processing techniques, features, and time-series classification models were analyzed. Across publications, a window length of one second was mainly chosen for classification and spectral features were utilized the most. The achieved performance per time-series classification model is analyzed, finding linear discriminant analysis, decision trees, and k-nearest neighbors models outperform support-vector machines by a factor of up to 1.5. A historical analysis depicts future trends while under-reported aspects relevant to practical applications are discussed. Five main conclusions are given, covering utilization of available area for electrode placement on the head, most often or scarcely utilized features and time-series classification model architectures, baseline reporting practices, as well as explainability and interpretability of Deep Learning. The importance of a 'test battery' assessing the influence of data pre-processing and multi-modality on time-series classification performance is emphasized.


Therapeutic and anti-inflammatory effects of baricitinib on mortality, ICU transfer, clinical improvement, and CRS-related laboratory parameters of hospitalized patients with moderate to severe COVID-19 pneumonia: a systematic review and meta-analysis.
Due to the high incidence and mortality of the worldwide COVID-19 pandemic, beneficial effects of effective antiviral and anti-inflammatory drugs used in other diseases, especially rheumatic diseases, were observed in the treatment of COVID-19. Clinical and laboratory parameters of eight included cohort studies and five Randomized Control Trials between the baricitinib group and the control group were analyzed on the first day of admission and days 7, 14, and 28 during hospitalization. According to the meta-analysis result of eight included cohort studies with 2088 patients, the Pooled Risk Ratios were 0.46 (P < 0.001) for mortality, 6.14 (P < 0.001) for hospital discharge, and the mean differences of 76.78 (P < 0.001) for PaO2/FiO2 ratio was -47.32 (P = 0.02) for CRP, in the baricitinib group vs. control group on the seventh or fourteenth day of the treatment compared to the first day. Based on the meta-analysis of five RCT studies with 11,825 patients, the pooled RR was 0.84 (P = 0.001) for mortality and 1.07 (P = 0.014) for patients' recovery. The mean differences were -0.80 (P < 0.001) for hospitalization days, -0.51(P = 0.33) for time to recovery in the baricitinib group vs. control group. Baricitinib prescription is strongly recommended in moderate to severe COVID-19.


Limitations of the Mini-Mental State Examination in predicting neuropsychological functioning in a psychiatric sample.
The present study examined the ability of the Mini-Mental State Examination (MMSE), a cognitive screening test commonly employed in research and clinical applications, to predict level of performance on a comprehensive neuropsychological battery, the Luria-Nebraska Neuropsychological Battery (LNNB). The tests were administered to a diagnostically mixed sample of 90 psychiatric inpatients. Correlations between the tests were statistically significant but modest and the MMSE was not able to detect many patients who demonstrated significant deficits on the LNNB. Additional correlational analyses between the MMSE and the Wechsler Adult Intelligence Scale-Revised in a subset of patients (n = 72) also showed a modest relationship between these instruments. The results suggest that the MMSE may seriously underestimate cognitive impairment in samples exclusively composed of psychiatric patients, making it inappropriate to rely solely on this instrument to distinguish psychiatric patients with and without cognitive deficit.


Atomic imaging of atomic layer deposition oxide nucleation with trimethylaluminum on As-rich InGaAs(001) 2 × 4 vs Ga/In-rich InGaAs(001) 4 × 2.
Formation of a contaminant free, flat, electrically passive interface to a gate oxide such as a-Al(2)O(3) is the critical step in fabricating III-V metal oxide semiconductor field effect transistors; while the bulk oxide is amorphous, the interface may need to be ordered to prevent electrical defect formation. A two temperature in situ cleaning process is shown to produce a clean, flat group III or group V rich InGaAs surface. The dependence of initial surface reconstruction and dosing temperature of the seeding of aluminum with trimethylaluminum dosing is observed to produce an ordered unpinned passivation layer on InGaAs(001)-(4 × 2) surface at sample temperatures below 190 °C. Conversely, the InGaAs(001)-(2 × 4) surface is shown to generate an unpinned passivation layer with a seeding temperature up to 280 °C. For both reconstructions, the chemical drive force is consistent with formation of As-Al-As bonds. The optimal seed layer protects the surface from background contamination.


Influence of pine or oak wood on the degradation of alachlor and metalaxyl in soil.
The objective of this work was to study the influence pine or oak wood added to soil as an amendment (5% w/w) had on the degradation rate of two pesticides, alachlor and metalaxyl, with different hydrophobic character. The formation of pesticide metabolites and the soil dehydrogenase activity in non-amended and amended soil samples were also monitored. The degradation of metalaxyl followed first-order kinetics, while the degradation of alachlor followed first-order or biphasic kinetics in the soil samples studied. The results indicated that the degradation rate was slower for metalaxyl than for alachlor, and for both pesticides followed the order: pine amended soil < oak amended soil < non-amended soil. The faster degradation rate in non-amended soil was attributed to the higher sorption of pesticides by wood amended soils. The alachlor ethane sulfonic acid (ESA), and two metalaxyl metabolites (2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid and N-(2,6-dimethylphenyl)-2-methoxy-acetamide) were detected during the incubation period. Soil dehydrogenase activity recorded close values in non-amended and amended soil treated with alachlor, but it was higher in wood amended soil treated with metalaxyl. Pine and oak wood increase the immobilization of the pesticides studied, but they also limit their bioavailability in soil by decreasing their degradation rate in amended soil.


[The Diagnostic Accuracy of Exercise Treadmill Testing and Stress Echocardiography for the Detection of Obstructive Coronary Artery Disease in Patients Aged ≥ 70 Years].
to compare diagnostic accuracy of exercise treadmill testing and stress echocardiography in the diagnosis of stable coronary artery disease (CAD) in patients aged >70 years. The study included 390 patients aged >70 years with suspected stable ischemic heart disease, who underwent elective coronary artery angiography (CAG). Exercise treadmill testing (ETT) according to the modified Bruce protocol was carried out in 189 patients (48 %), bicycle stress echocardiography - in 179 patients (46 %). Initially we determined the prevalence of angiographically significant CAD according to the gender and chest pain character, and identified persons in whom stress testing was appropriate. After that diagnostic accuracy of both tests was evaluated in patients with atypical angina and non-anginal chest pain. Among 72 patients with atypical angina and non-anginal pain who underwent ETT and had unequivocal results, 38 (53 %) had obstructive CAD. ETT for detection of obstructive CAD had sensitivity 79 %, specificity 82 %, positive likelihood ratio (LR+) 4.4, and negative likelihood ratio (LR-) 0.3. Positive result increased probability of obstructive CAD from 53 % to 83 %, negative result reduced probability of obstructive CAD to 25 %. Among 111 patients with atypical angina and non-anginal pain who underwent stress echocardiography and had unequivocal results, 69 (62 %) had obstructive CAD. Sensitivity, specificity, LR+, and LR- of stress echocardiography were equal to 89 %, 95 %, 17.8, and 0.1, respectively. Positive result increased probability of obstructive CAD from 62 % to 95 %, negative result reduced probability of obstructive CAD to 16 %. bicycle stress echocardiography was found to be more accurate than ETT to rule in or rule out obstructive CAD in patients aged ≥ 70 years with atypical angina and non-anginal pain.


Recurrence of melanoma in the scar after excised Spitz nevus in a 17-year-old child.
Melanoma in childhood is rare and its diagnosis is more difficult than in adults, as it often presents histologic features overlapping with the Spitz nevus. The authors report the case of a 17-year old boy who was first diagnosed with Spitz nevus, however, the final diagnosis made after the excision of the tumor arising in the scar was changed to melanoma. The case in this present study emphasizes the importance of the differential diagnosis of skin tumors in young patients.


Improving the management and outcomes of complex non-pedunculated colorectal polyps at a regional hospital in British Columbia.
Colorectal cancer arises from precancerous lesions, primarily adenomatous and serrated polyps. Some polyps pose significant technical endoscopic challenges due to their size, location, and/or morphology. A standardized protocol for documentation and management of these polyps can optimize clinical outcomes. A Quality Improvement project compared patients with a complex polyp (non-pedunculated, > 2 cm), for 12 months prior and 12 months after protocol introduction. Documentation and polyp management details were compared pre- and post-implementation using the Chi-square test. 69 patients were diagnosed with complex polyps prior to the protocol introduction and 72 after. 79% (112/141) of patients underwent endoscopic mucosal resections (EMR) locally, and 14.9% (21/141) underwent surgery locally. After protocol introduction, there was significant improvement in documentation of suspicious appearing polyps (21.7% to 47.2%, P = 0.001), luminal circumference (14.5% to 34.7%, P = 0.005), and management plans (87.0% to 97.2%, P = 0.023); other elements of documentation were similar. The number of patients reviewed at multidisciplinary conference (MDC) increased from 1 to 61% (P < 0.005). Patients rebooked in a 1 h endoscopy time slot increased from 19 to 58% (P < 0.005), as did specific consent for EMR from 22 to 57% (P < 0.005). Among patients with polyps 3 cm or greater (23 pre, 36 post), MDC review increased from 4 to 67% (P < 0.005), primary polypectomy decreased from 72 to 23% (P = 0.001), patients rebooked in a double endoscopy slot increased from 33 to 75% (P = 0.005), and specific consent increased from 39 to 75% (P = 0.014). There were less polyp recurrences (12/42 pre and 1/50 post) among the post-protocol cohort (P < 0.001). The introduction of a formalized protocol for complex polyp adjudication and management has led to improved documentation, multidisciplinary discussion, and optimal complex polyp management with dedicated time for EMR, particularly for polyps over 3 cm. There is room for improvement, and this can be approached in a collaborative manner.


Effect of NIH-IV prostatitis on free and free-to-total PSA.
To examine the effect of asymptomatic prostatic inflammation (NIH category IV prostatitis) on total PSA (tPSA), free serum PSA (fPSA) and the ratio of free-to-total prostate specific antigen (%fPSA). The role of free and %fPSA as a diagnostic tool for distinguishing between cancer and non-malignant diseases of the prostate was also investigated. In a retrospective study 1090 prostate biopsies performed between January 2000 and September 2003 were evaluated and the levels of serum total and free PSA as well as the f/tPSA ratio were determined in samples obtained immediately before biopsy. 404 patients with full clinical and histological records were included in the study. All patients underwent 6 or 8 core primary prostate needle biopsies. A total of 404 patients were included in the analysis. 100 prostate cancer (PCa) (24.8%), 137 NIH-IV prostatitis (33.9%) and 143 patients with benign prostatic hyperplasias (BPH) (35.4%) were identified. 24 (5.9%) patients presented with both PCa and prostatitis on histology and were excluded from further analysis. The mean (median) levels of tPSA, fPSA and %fPSA were 11.94 ng/ml (8.0), 1.31 ng/ml (1.07) and 0.15 (0.14) for NIH-IV prostatitis; 11.94 ng/ml (8.35), 1.54 ng/ml and 0.13 (0.11) for prostate cancer; and 8.19 ng/ml (7.0), 1.48 ng/ml (1.03) and 0.18 (0.15) for BPH. No significant difference was found in tPSA levels between PCa and prostatitis (p = 0.32), while the difference in tPSA levels between PCa and BPH was significant (p = 0.007). Free PSA alone had no diagnostic power in distinguishing PCa from prostatitis (p = 0. 37) and BPH (p = 0. 61). By contrast, the f/tPSA ratio showed significant between-group differences (PCa versus prostatitis (p = 0. 011), PCa versus BPH (p = 0.0001). Chronic asymptomatic prostatitis NIH category IV has similar effects on total PSA and free PSA levels in serum as PCa. fPSA alone cannot distinguish prostate cancer from non-malignant inflammatory disease of the prostate. The ratio of free-to-total PSA is significantly different in PCa and NIH category IV prostatitis.


Augmenting a Transitional Care Model With Artificial Intelligence Decreased Readmissions.
Evaluate if augmenting a transitions of care delivery model with insights from artificial intelligence (AI) that applied clinical and exogenous social determinants of health data would reduce rehospitalization in older adults. Retrospective case-control study. Adult patients discharged from integrated health system between November 1, 2019, and February 31, 2020, and enrolled in a rehospitalization reduction transitional care management program. An AI algorithm utilizing multiple data sources including clinical, socioeconomic, and behavioral data was developed to predict patients at highest risk for readmitting within 30 days and provide care navigators five care recommendations to prevent rehospitalization. Adjusted incidence of rehospitalization was estimated with Poisson regression and compared between transitional care management enrollees that used AI insights and matched enrollees for whom AI insights were not used. Analyses included 6371 hospital encounters between November 2019 and February 2020 across 12 hospitals. Of the encounters 29.3% were identified by AI as being medium-high risk for re-hospitalizing within 30 days, for which AI provided transitional care recommendations to the transitional care management team. The navigation team completed 40.2% of AI recommendations for these high-risk older adults. These patients had overall 21.0% less adjusted incidence of 30-day rehospitalization compared with matched control encounters, or 69 fewer rehospitalizations per 1000 encounters (95% CI 0.65‒0.95). Coordinating a patient's care continuum is critical for safe and effective transition of care. This study found that augmenting an existing transition of care navigation program with patient insights from AI reduced rehospitalization more than without AI insights. Augmenting transitional care with insights from AI could be a cost-effective intervention to improve transitional care outcomes and reduce unnecessary rehospitalization. Future studies should examine cost-effectiveness of augmenting transitional care models of care with AI when hospitals and post-acute providers partner with AI companies.


Islet encapsulation with polyphenol coatings decreases pro-inflammatory chemokine synthesis and T cell trafficking.
Type 1 Diabetes (T1D) is a chronic pro-inflammatory autoimmune disease consisting of islet-infiltrating leukocytes involved in pancreatic β-cell lysis. One promising treatment for T1D is islet transplantation; however, clinical application is constrained due to limited islet availability, adverse effects of immunosuppressants, and declining graft survival. Islet encapsulation may provide an immunoprotective barrier to preserve islet function and prevent immune-mediated rejection after transplantation. We previously demonstrated that a novel cytoprotective nanothin multilayer coating for islet encapsulation consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), was efficacious in dampening in vitro immune responses involved in transplant rejection and preserving in vitro islet function. However, the ability of (PVPON/TA) to maintain islet function in vivo and reverse diabetes has not been tested. Recent evidence has demonstrated that modulation of redox status can affect pro-inflammatory immune responses. Therefore, we hypothesized that transplanted (PVPON/TA)-encapsulated islets can restore euglycemia to diabetic mice and provide an immunoprotective barrier. Our results demonstrate that (PVPON/TA) nanothin coatings can significantly decrease in vitro chemokine synthesis and diabetogenic T cell migration. Importantly, (PVPON/TA)-encapsulated islets restored euglycemia after transplantation into diabetic mice. Our results demonstrate that (PVPON/TA)-encapsulated islets may suppress immune responses and enhance islet allograft acceptance in patients with T1D.


Disparities in health behaviors and outcomes at the intersection of race and sexual identity among women: Results from the 2011-2016 National Health and Nutrition Examination Survey.
The purpose of this study was to explore potential differences in health behaviors and outcomes of sexual minority women (SMW) of color compared to White SMW, heterosexual women of color, and White heterosexual women. Data from 4878 women were extracted from the 2011 to 2016 National Health and Nutritional Examination Survey. The four-category independent variable (SMW of color, White SMW, heterosexual women of color, and White heterosexual women) was included in binary and multinomial logistic regression models predicting fair/poor self-reported health status, depression, cigarette smoking, alcohol, cannabis, and illicit drug use. Compared to White heterosexual women, SMW of color and heterosexual women of color had significantly higher odds of fair/poor self-reported health and lower odds of being a current or former smoker, binge drinking or using alcohol in the past year, being a former cannabis user, and ever using illicit drugs. In contrast, White SMW had significantly greater odds of depression, current smoking and cannabis and illicit drug use. Results of post-hoc tests indicated that the adjusted ORs for SMW of color differed significantly from those of White SMW for all outcomes, and did not differ significantly from those for heterosexual women of color for any outcome other than no binge drinking (OR = 0.34 vs. 0.67, p < 0.01) and current cannabis use (OR = 0.93 vs. 0.44, p < 0.01). SMW of color are more similar to heterosexual women of color than to White SMW in terms of depression, substance use, and self-reported health.


Progestogen-induced alterations and their ecological relevance in different embryonic and adult behaviours of an invertebrate model species, the great pond snail (Lymnaea stagnalis).
The presence of oral contraceptives (basically applying estrogens and/or progestogens) poses a challenge to animals living in aquatic ecosystems and reflects a rapidly growing concern worldwide. However, there is still a lack in knowledge about the behavioural effects induced by progestogens on the non-target species including molluscs. In the present study, environmental progestogen concentrations were summarised. Knowing this data, we exposed a well-established invertebrate model species, the great pond snail (Lymnaea stagnalis) to relevant equi-concentrations (1, 10, 100, and 500 ng L-1) of mixtures of four progestogens (progesterone, drospirenone, gestodene, levonorgestrel) for 21 days. Significant alterations were observed in the embryonic development time, heart rate, feeding, and gliding activities of the embryos as well as in the feeding and locomotion activity of the adult specimens. All of the mixtures accelerated the embryonic development time and the gliding activity. Furthermore, the 10, 100, and 500 ng L-1 mixtures increased the heart rate and feeding activity of the embryos. The 10, 100, and 500 ng L-1 mixtures affected the feeding activity as well as the 1, 10, and 100 ng L-1 mixtures influenced the locomotion of the adult specimens. The differences of these adult behaviours showed a biphasic response to the progestogen exposure; however, they changed approximately in the opposite way. In case of feeding activity, this dose-response phenomenon can be identified as a hormesis response. Based on the authors' best knowledge, this is the first study to investigate the non-reproductive effects of progestogens occurring also in the environment on molluscan species. Our findings contribute to the global understanding of the effects of human progestogens, as these potential disruptors can influence the behavioural activities of non-target aquatic species. Future research should aim to understand the potential mechanisms (e.g., receptors, signal pathways) of progestogens induced behavioural alterations.


Effect of Preparation Based on Trametes Pubescens Xylotroph Fungi on Lipid Peroxidation in the Blood of Experimental Animals under Conditions of Dark Stress.
Using the model of dark stress caused by animal maintenance at dimmed light we showed that Trametin (product obtained during liquid-phase culturing of Trametes pubescens xylotroph fungi) effectively prevented oxidative stress under conditions of light deprivation. The preparation increased the level of unsaturation of lipids, reduced the concentration of primary and end-products of LPO, and increases both the integral parameter of the antioxidant defense system (total antioxidant activity) and its components (activity of superoxide dismutase and reduced glutathione).


Hashish smoking and T-lymphocytes.
To investigate the effect of long term hashish use on T-lymphocytes we have measured the incorporation of 14C-thymidine by peripheral blood lymphocytes, unstimulated and stimulated by phytohemagglutinin, as well as the proportion and number of E-rosettes in 12 healthy male chronic users of the drug before and after a smoking session, and in 15 control subjects. The results show that hashish smoking does not impair the response of lymphocytes to PHA, at least at the concentration of PHA used. Furthermore there is a possibility that among chronic users a hashish smoking session may have a slight stimulatory effect.


The effect of potassium and venous CO2 loading on chemoreceptor firing in anaesthetized cats.
The CO2 production of 5 anaesthetized cats, ventilated to a constant PaCO2 and PaO2 by appropriate alteration of tidal volume and FIO2, was altered by means of an extracorporeal gas exchanger. Afferent chemoreceptor discharge was recorded from a single fibre preparation of the right carotid sinus nerve and the respiratory oscillations in firing were derived over 50 breath (2.5 min) periods. In response to an approximate doubling of CO2 production the discharge oscillation showed an increase in amplitude (P less than 0.05) but no change in mean level. When KCl was infused to produce a mean arterial [K+] of 5.9 mmol/L, while maintaining the same level of CO2 loading, the amplitude of the oscillation increased from 2.9 +/- 0.5 impulses/sec to 5.2 +/- 1.0 impulses/sec (P less than 0.05) and the mean increased from 2.6 +/- 0.4 impulses/sec to 3.9 +/- 0.2 impulses/sec (P less than 0.01). The implications of these findings are discussed.


Cauda equina compression post lumbar discography.
Discography is used as an aid in the diagnosis of back pain related to intervertebral disc pathology. It involves attempting to elicit the patient's pain symptoms by injecting contrast into the suspected pathological disc. The overall complication rate of discography is low, with discitis being the most common complication and acute disc herniation post lumbar discography being reported in a small number of cases. We describe the case of a patient who developed cauda equina compression post lumbar discography.


Coupled and uncoupled limb oscillations during paw-shake response.
Intersegmental limb dynamics and muscle activities were analyzed for consecutive cycles of paw-shake responses from chronic-spinalized cats to investigate how hindlimb trajectories organize into a pattern with regular oscillations, a steady-state response, or alternatively, into a pattern with irregular oscillations, a nonsteady-state response. In the spinalized preparation, steady-state and nonsteady-state responses have an equal likelihood of emerging from the initial cycles of a paw-shake response, suggesting that regular coupling of joint oscillations is not planned by pattern-generating networks within lumbosacral segments. To examine the characteristics of coupled and uncoupled limb oscillations during paw-shake responses, we assessed patterns of muscle activity and hindlimb kinematics of six adult chronic-spinalized cats. Additionally, we used inverse-dynamics techniques to quantify the intersegmental dynamics of the paw, leg, and thigh. Our data indicate that by the second cycle of both steady-state and nonsteady-state responses, the basic pattern of interaction between muscle and motion-dependent torques at the ankle and knee joints was established. During subsequent cycles of steady-state responses, a consistent sequence of timing changes occurred, such that, just prior to steady-state oscillations, torque maximums peaked simultaneously at each joint and joint reversals occurred simultaneously. Although nonsteady-state responses showed a similar sequence during beginning cycles, increased ankle muscle and net torques during middle cycles created larger inertial torques at the knee joint that were not counteracted and resulted in irregular and uncoupled knee oscillations. It is likely that neither steady-state nor nonsteady-state oscillations are planned by pattern-generating networks within lumbosacral segments, but that patterns of interjoint coordination emerge from the coupling among oscillators. For paw-shake responses in the spinalized preparation, coupling may depend on interactions between central circuits and motion-dependent feedback that is necessary to stabilize inertial effects due to large ankle joint accelerations.


Regional intra-arterial infusion of cisplatin in primary hepatocellular carcinoma. A phase II study.
Ten consecutive adults with localized nonresectable hepatocellular carcinomas were selected as a nonrandom sample for an investigation into the effectiveness of cisplatin (DDP) as a single agent when administered regionally via the hepatic artery from 1981 to 1984. The dose of DDP was 50 mg/m2 (normally, 80 mg). Complete remission (CR) was observed in one patient, partial remission (PR) in three patients, and in five patients, there were no significant changes in tumor size; the disease progressed in one patient. The mean period of survival of the group was 19.7 months. All patients suffered from severe nausea and vomiting, ordinarily until the afternoon of the day after treatment. One patient died of uremia, which related to the cytostate. The authors consider cisplatin useful in the intra-arterial treatment of hepatocellular carcinoma with favorable prognostic factors in patients for whom surgical treatment is not suitable.


HEMOGLOBIN POLYMORPHISMS IN DEER MICE (PEROMYSCUS MANICULATUS): PHYSIOLOGY OF BETA-GLOBIN VARIANTS AND ALPHA-GLOBIN RECOMBINANTS.
Wild populations of deer mice (Peromyscus maniculatus) contain hemoglobin polymorphisms at both alpha-globin (Hba, Hbc) and beta-globin (Hbd) loci. Population gene frequencies of beta-globin variants (d0 and d1 haplotypes) are not correlated with altitude, whereas a1 c1 alpha-globin haplotypes are fixed in low-altitude populations, and a0 c0 haplotypes reach near fixation at high altitudes. We examined the effects of alpha- and beta-globin variants on blood oxygen affinity and on aerobic performance, measured as maximum oxygen consumption (V˙O2max). Exercise and cold exposure were used to elicit V˙O2max. Experiments were performed at low (340 m) and high (3,800 m) altitude to include the range of oxygen partial pressures encountered by wild deer mice. Beta-globin variants had little effect on blood oxygen affinity or V˙O2max. Oxygen-dissociation curves from a0 c0 and a1 c1 homozygotes and heterozygotes had similar shapes, but the P50 of a0 c0 homozygotes was significantly lower than that of other genotypes. Mice carrying a1 c1 /a1 c1 genotypes had the highest V˙O2max at low altitude, but mice with a0 c0 /a0 c0 genotypes had the highest V˙O2max at high altitude. Mice carrying rare recombinant alpha-globin haplotypes (a0 c1 ) had lower V˙O2max than nonrecombinant genotypes as a whole but in most cases were not significantly different from nonrecombinant heterozygotes (a0 c0 /a1 c1 ). We conclude that genetic adaptation to different altitudes was important in the evolution of deer mouse alpha-globin polymorphisms and in the maintenance of linkage disequilibrium in the alpha-globin loci but was not a significant factor in the evolution of beta-globin polymorphisms.


Reduced shoulder strength and change in range of motion are risk factors for shoulder injury in water polo players.
To determine whether pre-season shoulder ROM and strength can be used to identify athletes at risk of future shoulder injury. Prospective cohort. High performance sports institute. 76 sub-elite water polo players. Mean pre-season shoulder internal (IR) and external rotation (ER) ROM and strength values compared by gender, dominance and prospective injury status. 14-dominant shoulder injuries were recorded. There was a significant difference (p = 0.05) in total ROM difference (TROM) between the prospectively injured and no injury groups (-17.2°(30.4);-0.8°(13.3)), and dominant side ER strength (11.7%(2.4) vs 14.5%(2.8), p = 0.03) and IR strength (16.5%(3.0) vs 21.6%(4.9) as a percentage body weight (PBW) were also significantly different (p ≤ 0.03). Separate significant associations were found between future episodes of shoulder injury and; dominant shoulder TROM difference of ≥7.5°(OR 3.6,95%CI 0.8-16.0), ER strength as a PBW≤12.5%(OR 5.2,95%CI 1.0-27.9), and IR strength as a PBW≤16.8%(OR 13.8,95%CI 2.2-88.0). Pre-season dominant TROM difference, and reduced shoulder IR and ER strength relative to body weight were significant predictors for future shoulder injury. Although further investigation with a larger sample size is required, achieving optimal values on these measures may reduce future episodes of shoulder injury in water polo players.


Autonomous robots: a new reality in healthcare? A project by European Association of Urology-Young Academic Urologist group.
Artificial intelligence appears as a potential revolution in the general process of medical training, disease diagnosis and treatment. A novel disruptive technology of the 21st century will be 'learner' robots from artificial intelligence systems able to use all the combination of the available knowledge in medical repositories to give the best standard of care. The autonomy level of robots depends on three factors: the complexity of the task; the environment in which the robot operates, and the required level of human-robot interaction. Autonomous robots in healthcare may be classified in delivery, nurse, and surgical robots. The increasing capability of robots to perform independent actions and complex tasks raises responsibility and accountability issues in a wide variety of application domains. Ethical analyses of these issues are underway and are mostly oriented toward the development of ethical policies requiring a law frame on robotic autonomous behaviors. Autonomous robots have the potential to improve current medical practice offering a more secure, reliable, and reproducible medicine. Many advancements are required for these new technologies to be fully integrated. Furthermore, the ethical implications of these technologies are yet to be evaluated.


Domoic acid-induced neuronal degeneration in the primate forebrain revealed by degeneration specific histochemistry.
Domoic acid is a potent excitotoxin produced by diatoms which is subsequently passed along the marine food chain. Its chemical structure and toxicological properties are similar to kainic acid. Like kainic acid, exposure results in extensive hippocampal degeneration. The effect of domoic acid on other primate brain structures, however, is less resolved. In an attempt to clarify this issue, the present study applied a degeneration specific histochemical technique (de Olmos' cupric-silver method) to reveal degeneration within the brains of domoic acid-dosed cynomolgus monkeys. Degenerating neuronal cell bodies and terminals were found not only within the hippocampus, but also within a number of other 'limbic' structures including the entorhinal cortex, the subiculum, the piriform cortex, the lateral septum, and the dorsal lateral nucleus of the thalamus. Although the hippocampus is a component of the original limbic circuit of Papez, other components such as the mammillary bodies, the anterior nucleus of the thalamus and the cingulate cortex contained no degeneration, while a number of more recently documented efferent targets of the hippocampal formation revealed extensive degeneration. The pattern of degeneration generally correlated with those regions containing high densities of kainate receptors.


Towards a science of informed matter.
Over the last couple of decades, a call has begun to resound in a number of distinct fields of inquiry for a reattachment of form to matter, for an understanding of 'information' as inherently embodied, or, as Jean-Marie Lehn calls it, for a "science of informed matter." We hear this call most clearly in chemistry, in cognitive science, in molecular computation, and in robotics-all fields looking to biological processes to ground a new epistemology. The departure from the values of a more traditional epistemological culture can be seen most clearly in changing representations of biological development. Where for many years now, biological discourse has accepted a sharp distinction (borrowed directly from classical computer science) between information and matter, software and hardware, data and program, encoding and enactment, a new discourse has now begun to emerge in which these distinctions have little meaning. Perhaps ironically, much of this shift depends on drawing inspiration from just those biological processes which the discourse of disembodied information was intended to describe.


Premature differentiation of vascular smooth muscle cells in human congenital diaphragmatic hernia.
Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterized by the herniation of abdominal organs into the chest cavity. The high mortality and morbidity of CDH patients are primarily caused by the associated pulmonary hypertension (PH), characterized by the thickening of the vascular media and adventitia. The media consist of heterogeneous populations of vascular smooth muscle cells (VSMC), ranging from synthetic to the characteristic contractile cells. VSMCs are influenced by developmental and environmental cues and may play a role in the development of the structural changes observed in CDH patients. Therefore, we hypothesized that the distribution of the VSMC populations may already be different at the origin of CDH development. We analyzed the protein expression of specific markers associated with synthetic and contractile VSMC phenotypes in human lungs at different developmental stages. Next, we compared lungs of premature and term CDH patients, as well as patients with lung hypoplasia due to renal agenesis or PROM, with age-matched controls. Synthetic and contractile VSMCs are distributed in a temporal and spatial specific pattern along the proximodistal axis of the lung. CDH patients have more abundant contractile VSMCs which are also more distally distributed. This different distribution pattern is already observed from 19 weeks of gestation onwards. Our data suggest that the more extensive distribution of contractile VSMCs is associated with an early maturation of the pulmonary vasculature, contrasting the concept that CDH might be the result of delayed maturation of the epithelium.


Effect of ultrasonic treatment on the structure and functional properties of mantle proteins from scallops (Patinopecten yessoensis).
In this study, scallop mantle protein was treated by ultrasound at different powers, and then analyzed by ANS fluorescent probes, circular dichroism spectroscopy, endogenous fluorescence spectrum, DNTB colorimetry and in-vitro digestion model to elucidate the structure-function relationship. The results indicated that ultrasound can significantly affect the secondary structure of scallop mantle protein like enhancing hydrophobicity, lowering the particle size, increasing the relative contents of α-helix and decreasing contents of β-pleated sheet, β-turn and random coil, as well as altering intrinsic fluorescence intensity with blue shift of maximum fluorescence peak. But ultrasound had no effect on its primary structure. Moreover, the functions of scallop mantle protein were regulated by modifying its structures by ultrasound. Specifically, the protein had the highest performance in foaming property and in-vitro digestibility under ultrasonic power of 100 W, oil binding capacity under 100 W, water binding capacity under 300 W, solubility and emulsification capacity under 400 W, and emulsion stability under 600 W. These results prove ultrasonic treatment has the potential to effectively improve functional properties and quality of scallop mantle protein, benefiting in comprehensive utilization of scallop mantles.


A perfusion technique for 13C NMR studies of the metabolism of 13C-labeled substrates by mammalian cells.
We describe an improved perfusion system designed for NMR studies with 13C-labeled metabolites. Using this system we have monitored the uptake and metabolism of [13C]acetate and [13C]glucose in pooled human lymphocytes cast in an agarose gel thread.


Digestive enzyme activities in herbivorous and carnivorous prickleback fishes (Teleostei: Stichaeidae): ontogenetic, dietary, and phylogenetic effects.
We measured the activities of eight digestive enzymes in four species of herbivorous and carnivorous prickleback fishes and determined the effects of ontogeny, diet, and phylogeny on these enzyme activities. Of the four species, Cebidichthys violaceus and Xiphister mucosus shift to a more herbivorous diet as they grow (> or =45 mm SL [standard length]), whereas Xiphister atropurpureus and Anoplarchus purpurescens remain carnivores throughout life. Digestive enzyme activities of small (30-40 mm SL) carnivorous juveniles were compared with those of larger (60-75 mm SL) wild-caught juveniles that had consumed a natural diet and larger (60-75 mm SL) juveniles raised on a high-protein animal diet. Cebidichthys violaceus and both species of Xiphister showed ontogenetic changes in digestive enzyme activities, whereas A. purpurescens did not. Despite dietary differences between X. atropurpureus and X. mucosus, these sister taxa displayed the most similar digestive enzyme activities from ontogenetic and dietary perspectives (high alpha-amylase and lipase and low trypsin and aminopeptidase activities), and both were more similar to C. violaceus, a member of the same largely herbivorous clade, than either was to A. purpurescens, a member of an adjacent, carnivorous clade. The results support the hypothesis that phylogeny influences digestive enzyme activities in these fishes. Anoplarchus purpurescens, a carnivore with a diverse diet, showed great plasticity in enzyme activity, especially trypsin and aminopeptidase, which were elevated in this species to the highest level among the four species after consuming the high-protein diet. These results support the hypothesis that fishes with relatively broad diets can modulate digestive enzyme activities in response to changes in dietary composition.


A modulator against mercury chloride-induced genotoxic damage: Dermatocarpon intestiniforme (L.).
Mercury has been used in many domains of human activities for many years, although in any form mercury is reported to be toxic. On the other hand, lichens have been used in the treatment of several diseases such as tuberculosis, hemorrhoids, ulcer, dysentery and cancer. Animal investigations on some common lichen species have demonstrated their antioxidant and antimutagenic activity. However, there is very scarce data on the medical or biologic effects of specific lichen species. Therefore, in the present study, we assessed the cyotogenetic effects of mercuric chloride (HgCl(2)) and the role of aqueous Dermatocarpon intestiniforme lichen extracts in mercury-treated human blood cultures (n = 3). The sister chromatid exchange (SCE) and micronucleus (MN) assays were performed to assess DNA damages in lymphocytes. Our results clearly revealed that the SCE and MN rates induced by HgCl(2) were alleviated by the presence of D. intestiniforme. In conclusion, the results of the present study revealed for the first time that the lichen D. intestiniforme provided increased resistance of DNA against HgCl(2)-induced genetic damage on human lymphocytes.


Anti-beta1 integrin antibody reduces surgery-induced adhesion of colon carcinoma cells to traumatized peritoneal surfaces.
To study the mechanisms behind surgery-induced augmentation of tumor outgrowth. Surgery provides the best chance of cure for most primary intra-abdominal carcinomas. Effective treatment is however relatively frequent complicated by peritoneal recurrences, which often originate from free-floating intraperitoneal tumor cells that implant on peritoneal surfaces. We previously reported that surgical trauma promotes development of peritoneal metastases. Evaluation of adhesion of CC531s rat colon carcinoma cell line intraperitoneally after laparotomy using in vivo, ex vivo, and in vitro models. Also, human ex vivo models were used to study peritoneal tumor cell adhesion. Peritoneal imprints of operated rats showed that direct damaging of the peritoneum resulted in enhanced adhesion of rat CC531 colon carcinoma cells to submesothelial extracellular matrix (ECM) proteins in vivo, which was confirmed by electron microscopy. Additionally, the inflammatory reaction of the peritoneal cavity led to retraction of mesothelial cells, hereby also exposing ECM at peritoneal surfaces that had not been traumatized directly. Furthermore, we demonstrated that beta1 integrin subunits represented the primary mediators involved in adherence to either isolated ECM components or excised traumatized rat and human peritoneum. Importantly, incubation of CC531s cells with anti-beta1 integrin antibodies resulted in a significant decrease of tumor cell adhesion in vivo. Surgical trauma results in exposure of ECM at directly and nondirectly damaged peritoneal surfaces, leading to increased beta1 integrin-dependent tumor cell adhesion. Perioperative therapies, which aim to block beta1 integrin subunits, might therefore serve as new clinical tools for the prevention of peritoneal recurrences.


Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study.
Normal cellular metabolism is well established as the source of endogenous reactive oxygen species which account for the background levels of oxidative DNA damage detected in normal tissue. Hydrogen peroxide imposes an oxidative stress condition on cells that can result in DNA damage, leading to mutagenesis and cell death. Several potentially significant genetic variants related to oxidative stress have already been identified, and angiotensin I-converting enzyme (ACE) inhibitors have been reported as possible antioxidant agents that can reduce vascular oxidative stress in cardiovascular events. We investigate the influences of haptoglobin, manganese superoxide dismutase (MnSOD Val9Ala), catalase (CAT -21A/T), glutathione peroxidase 1 (GPx-1 Pro198Leu), ACE (I/D) and gluthatione S-transferases GSTM1 and GSTT1 gene polymorphisms against DNA damage and oxidative stress. These were induced by exposing leukocytes from peripheral blood of healthy humans (N = 135) to hydrogen peroxide (H2O2), and the effects were tested by comet assay. Blood samples were submitted to genotyping and comet assay (before and after treatment with H2O2 at 250 microM and 1 mM). After treatment with H2O2 at 250 microM, the GPx-1 polymorphism significantly influenced results of comet assay and a possible association of the Pro/Leu genotype with higher DNA damage was found. The highest or lowest DNA damage also depended on interaction between GPX-1/ACE and Hp/GSTM1T1 polymorphisms when hydrogen peroxide treatment increased oxidative stress. The GPx-1 polymorphism and the interactions between GPX-1/ACE and Hp/GSTM1T1 can be determining factors for DNA oxidation provoked by hydrogen peroxide, and thus for higher susceptibility to or protection against oxidative stress suffered by healthy individuals.