Relation of left ventricular dilation during acute myocardial infarction to systolic performance, diastolic dysfunction, infarct size and location.
The quantification of left ventricular (LV) volumes and assessment of their relation to systolic and diastolic dysfunction, infarct size and anatomic location were performed in 54 patients with a first acute myocardial infarction (AMI). Blood pool radionuclide angiography was used to assess LV end-diastolic, end-systolic, and stroke volume indexes, ejection fraction and peak diastolic filling rate. Infarct size was estimated from plasma MB creatine kinase activity. Substantial LV dilation occurred within the initial 24 hours of AMI. The peak diastolic filling rate was low, even in those patients with a normal ejection fraction. In comparison with inferior AMI (n = 25), patients with anterior AMI (n = 29) had a larger end-diastolic volume index (105 +/- 8 vs 81 +/- 4 ml/m2, p less than 0.01) and end-systolic volume index (64 +/- 7 vs 37 +/- 4 ml/m2, p less than 0.001), but similar stroke volume index (41 +/- 3 vs 43 +/- 2 ml/m2, difference not significant). No significant relation was noted between infarct size estimated by MB creatine kinase and any volumetric index. On repeat study (day 10 after AMI), end-diastolic and end-systolic volume indexes increased further (p less than 0.05 vs day 1) but ejection fraction and peak diastolic filling rate were unchanged. It was concluded that: (1) LV dilation occurs within hours of AMI in both inferior and anterior AMI, but is more marked in the latter; (2) significant LV diastolic dysfunction is the rule, even in patients with preserved LV systolic function; and (3) LV dilation is an early compensatory mechanism that maintains normal stroke volume, even in patients with severely reduced LV function.


Simulation of highly efficient GeSe-based solar cells with SCAPS-1D.
Recently GeSe has developed as a promising light harvesting material by enjoying to its optical and electrical features as well as earth-abundant and low-toxic constituent elements. Nevertheless, the power conversion efficiency of GeSe-based solar cells yet lags far behind the Shockley-Queisser limit. In this work, we systematically designed, simulated and analyzed the highly efficient GeSe thin-film solar cells by SCAPS-1D. The influence of thickness and defect density of light harvest material, GeSe/CdS interface defect density, electron transport layer (ETL), electrode work function and hole transport layer (HTL) on the device output are carefully analyzed. By optimizing the parameters (thickness, defect, concentration, work function, ETL and HTL), an impressive PCE of 17.98% is delivered along with Jsc of 37.11 mA/cm2, FF of 75.53%, Voc of 0.61 V. This work offers theoretical guidance for the design of highly efficient GeSe thin film solar cells.


[Pharmacolymphography].
With the goal of accelerating the contrast-medium injection at the lymphography and improving the contrasting of the vessels and node conduction system the authors applied a variety of pharmacological preparations: Ridol (G. Richter), Nospanum (Quinoine, HPR), Arfonadum (Hoffman-La Rochet, Switzerland), Xavinum (Quinoine) etc. in 110 cases of various malignant neoplasms. All the selected drugs are, to a greater or lesser extent, of a vasodilative effect. It has been found that Ridol together with the combination of Novocaine and Nospanum produce a pronounced lymphotropic effect. Pharmacolymphography with these preparations contributes to the shortening of the time necessary for the injection of contrast-medium and also improves the image of the intermediate node sinuses and of the thoracic duct.


Implantable Electrical Stimulation at Dorsal Root Ganglions Accelerates Osteoporotic Fracture Healing via Calcitonin Gene-Related Peptide.
The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene-related peptide (CGRP) by activating Ca2+ /CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type-H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES-enhanced osteoporotic fracture healing. This proof-of-concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration.


Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: a Gynecologic Oncology Group study.
Excision repair cross-complementation group 1 (ERCC1) is required for the repair of platinum-induced DNA damage. This study sought to assess the prognostic value of ERCC1 expression, measured by immunohistochemistry (IHC) using a highly specific antibody, in advanced epithelial ovarian cancer (EOC) patients treated with platinum-based chemotherapy. Formalin-fixed, paraffin-embedded tumors were collected from two GOG phase III trials (GOG-172 and GOG-182) of patients with stage III/IV EOC treated with platinum-based chemotherapy. ERCC1 was detected by (IHC) using FL297 polyclonal antibody and tumors were categorized as negative or positive, based on nuclear staining of tumor cells. ERCC1 genotyping was performed as previously reported. Associations between ERCC1 expression and clinical characteristics, platinum responsiveness, progression-free survival (PFS) or overall survival (OS) were evaluated. Of 408 eligible patients, 27% had tumors that were ERCC1 positive. ERCC1 expression was not associated with clinical characteristics or platinum-responsiveness. Women with ERCC1-positive versus -negative tumors had similar median PFS (17.9 months versus 17.5 months, respectively, p=0.59), median OS (52.0 months versus 47.0 months, respectively, p=0.30), risk of disease progression (adjusted hazard ratio [HR]=0.90, 95% confidence interval (CI): 0.71-1.15, p=0.41), and risk of death (adjusted HR=0.81, 95% CI: 0.61-1.07, p=0.14). ERCC1 expression, as measured by IHC, was not associated with single nucleotide polymorphisms (SNPs), in codon 118 and C8092A, of the ERCC1 gene. ERCC1 expression, measured by IHC in pre-treatment tumor specimens, using a highly specific antibody, has limited clinical value in patients with advanced EOC treated with platinum and taxane based chemotherapy.


Surveying perceptions of the early impacts of an integrated electronic medical record across a hospital and healthcare service.
Objective This study provides insights into the reported early impacts of the digital transformation of a large Australian hospital and healthcare service (HHS) by surveying staff perceptions of an integrated electronic medical record (ieMR). Methods The information systems success model was used as a tool to evaluate perceptions of system quality, information quality, individual benefits and expected organisational benefits of the ieMR soon after its introduction at the HHS. A questionnaire was distributed to staff in all five hospitals in the HHS immediately after implementation. Overall staff perceptions were examined, in addition to how perceptions differed by site and profession. Results Overall, staff held mildly positive early perceptions of system quality, information quality, individual benefits and expected organisational benefits. These views were largely consistent across sites. In terms of professions, allied health held more positive perceptions, followed by administrative and nursing professionals. Medical professionals held negative perceptions, but were neutral regarding their future expectations. Conclusion On average, staff viewed the ieMR mildly positively immediately after implementation (despite significant changes to work practices), but differences exist across professional groups. What is known about the topic? Hospitals globally are in the midst of a digital transformation. Yet, reported impacts are mixed and there have been few studies of the effects of comprehensive electronic medical record (EMR) implementations. What does this paper add? This paper evaluates a comprehensive EMR immediately after go-live. We found positive early perceptions of system quality, information quality, individual benefits and expected organisational benefits. We also found that perceptions of medical professionals were largely negative, but they were neutral in terms of their future expectations. What are the implications for practitioners? Health services may be unsure of the effect of implementing a comprehensive EMR because of conflicting reports in the literature, some touting major benefits, others stressing major costs. Our results paint a middle-ground picture immediately after implementation. Staff perceptions are mildly positive on average, which is reassuring given the results were obtained during the early disruptive period after implementation.


Vascular access surgery as an outpatient procedure.
Construction of a vascular access site for hemodialysis has traditionally been done on an inpatient basis or more recently in a hospital operating room as a 1-day admission. Over 18 months we performed 49 vascular access procedures on 45 patients in a freestanding ambulatory surgical center. Four patients had an arteriovenous radiocephalic autogenous fistula constructed, 30 patients had a polytetrafluoroethylene (PTFE) prosthesis inserted as an arteriovenous bridge graft, 11 patients had a planned reconstruction of a previously placed graft, 1 patient had a false aneurysm corrected, 1 patient had a chronically infected graft removed, and 2 patients had a thrombectomy. All procedures were in the upper extremities except for one femorosaphenous PTFE graft and one excision of a false aneurysm in a thigh prosthesis. Only one patient, an 84-year-old woman, required hospitalization following the outpatient procedure because she was unable to care for herself. No postoperative infection had occurred at 1 month follow-up. A left upper extremity graft performed at another inpatient facility was removed because of infection. The protocol for outpatient vascular access surgery includes preoperative evaluation of the patient for determination of the access site within a week of operation; duplex scan of subclavian veins if central venous lines have been in place for more than 2 weeks; scheduling surgery for the afternoon or morning following routine hemodialysis; obtaining a hemoglobin level, serum/electrolyte study, and an ECG following the last hemodialysis; parenteral antimicrobial prophylaxis; local infiltration anesthesia with standby; a minimum of 1 hour of observation in the recovery room; and a repeat hematocrit study prior to discharge.(ABSTRACT TRUNCATED AT 250 WORDS)


Body temperature rhythms and activity in reproductive Antechinus (Marsupialia).
To determine whether locomotor activity and body temperature (Tb) rhythms change during the mating season of male Antechinus stuartii and whether that could contribute to postmating die-off, we measured both variables in individuals kept in the laboratory under natural photoperiod. Before the mating season Antechinus were mainly nocturnal. However, during the mating period (end of August) males showed a markedly elevated activity level and some animals extended their activity period well into the light phase. After about 2 weeks, normal activity patterns were restored. Activity was always accompanied by elevated TbS, whereas resting phases were characterized by low TbS. During the mating season the average daily Tb was increased because animals maintained high TbS for longer time periods and because the resting Tb was also elevated. The rise of both Tb and locomotor activity during the mating season indicate an enhanced energy expenditure even when agonistic encounters between males and mating are excluded. However, under laboratory conditions without severe cold stress, food ad lib, and without social interaction males were able to avert postmating die-off.


Incidence of Inner Ear Disorders in Various Forms of Acute Otitis Media in ENT Practices in Germany.
The aim of this study was to determine the incidence of inner ear involvement in various forms of acute otitis media (AOM) in ear, nose, and throat (ENT) practices in Germany. Patients who had been diagnosed with various forms of AOM in the years 2010 to 2017 were enrolled in the study from a nationwide, representative practice database (Disease Analyzer, IQVIA). In these patients, the incidence of simultaneous or subsequent inner ear disorders (IED) was determined within 7 days and within 12 months from the date of an AOM diagnosis. A total of 286 186 patients with AOM were enrolled. The most frequent diagnoses were "nonsuppurative otitis media, unspecified" (47.6%) and "otitis media, unspecified" (39.0%). The diagnoses of hemorrhagic bullous myringitis (BM) or influenza-induced AOM were very rarely found in the database. The highest incidence of IED after 7 days and 12 months was found in "nonsuppurative otitis media, unspecified" (7.7% and 15.9%, respectively), followed by "otitis media, unspecified" (5.6% and 13.5%, respectively). The incidences of the most frequent IED "hearing loss, unspecified" and "sensorineural hearing loss, unspecified" increased proportionally with increasing patient age, while the rare diagnoses of "labyrinthitis" and "ototoxic hearing loss" were evenly distributed among the age groups. In ENT practices in Germany, both various forms of AOM, as well as simultaneous or subsequent IED, are mostly being coded in an unspecific way, while specific forms such as hemorrhagic BM, influenza-induced AOM, and labyrinthitis are coded very rarely. Older patients have a higher risk of IED in AOM. A visit due to AOM seems to be a regular occasion for the initial diagnosis of hearing impairment in the elderly individuals. The highest risk of IED was found in nonsuppurative AOM.


Eccentric rheometry for viscoelastic characterization of small, soft, anisotropic, and irregularly shaped biopolymer gels and tissue biopsies.
Quantification of the physical properties of tissue biopsies and cell-remodeled hydrogels is critical for understanding tissue development and pathophysiological tissue remodeling. However, due to the low modulus, small size, irregular shape, and anisotropy of samples from these materials, accurate viscoelastic characterization using standard rheometric methods is problematic. The goal of this work is to utilize image analysis to extend rotational rheometry to these samples. In this method, the sample is offset to increase the torque generated; a custom clear glass geometry, right angle prism, and camera are used to determine the exact shape and location of the sample relative to the axis of rotation for calculation of the sample shear modulus, G'. Values of G' for standard polydimethylsiloxane gels tested in centered and eccentric configurations were not statistically different (respectively 137 ± 37 kPa and 126 ± 8 kPa, p = 0.58), indicating accuracy of the method. Additionally, G' values from circular and irregularly shaped collagen gels yielded equivalent results (31 ± 1.8 Pa and 31 ± 5.1 Pa, p = 0.29). A blood clot and a lipid plaque sample recovered from human patients (G' ~ 4 kPa) were successfully tested with this method demonstrating applicability to clinical diagnostics.


What are the correlates of cognition and participation to return to work after first ever mild stroke?
The percentage of working age people with mild stroke has risen. Evidence indicates that even mild stroke impact cognition, executive functioning, and daily functioning, consequently affecting participation, quality of life (QoL) and return to work (RTW). (1) Compare cognition, participation and QoL between people 3 months post-mild stroke who RTW and those who did not; and (2) To determine the correlates of these variables to RTW of participants 3 months post-stroke. We visited at home 163 stroke survivors (117 men, 46 women) 3 months post-mild stroke ranging from 50 to 89 years. Participants who returned to work (n = 114) and those who did not (n = 49). Data collection at home included measures for cognitive status (MoCA), executive functions (EFPT, DEX), depression (GDS), participation (RNL), and QoL (SIS recovery). Significant differences were found between RTW participants and those who did not RTW in measures of cognition, depression, participation and QoL (t = 2.36 to - 5.62, P < 0.022-0.001). No difference was found on age or gender. Stepwise regression showed that significant correlates of RTW were participation (RNL), executive functions (EFPT), and QoL (SIS recovery). To enable RTW after mild stroke, participation, executive functions and QoL must be considered in planning interventions.


Novel lipidomes profile and clinical phenotype identified in pneumoconiosis patients.
Pneumoconiosis is a group of occupational lung diseases caused by the inhalation of mineral dust in the lungs, leading to lung dysfunction. Patients with pneumoconiosis are usually accompanied by weight loss, which suggests a lipid metabolism disorder. Recent progress in lipidomics uncovered detailed lipid profiles that play important roles in respiratory diseases, such as asthma, lung cancer and lung injury. The purpose of this study was to shed light on the different expression of lipidome between pneumoconiosis and healthy, hoping to bring new ideas for the diagnosis and treatment of pneumoconiosis. This non-matching case-control study was performed among 96 subjects (48 outpatients with male pneumoconiosis and 48 healthy volunteers), data of clinical phenotypes were recorded, and plasma biochemistry (lipidomic profiles) was tested for both pneumoconiosis patients and healthy controls. A total of 426 species in 11 lipid classes were analyzed by high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QqQ-MS) for the cases and controls. We also analyzed the correlation of lipid profiles with clinical phenomes from pneumoconiosis patients by expression quantitative trait locus (eQTL) model to evaluate trans-nodules between lipidomic profiles and clinical phenomes. All visually re-checked data were analyzed using appropriate statistical tools (t-test or one-way ANOVA test) on SPSS. Compared with healthy people, 26 significantly increased (> 1.5-fold) and 30 decreased lipid elements (< 2/threefold) in patients with pneumoconiosis were identified (P values all < 0.05). The majority of those elevated lipid elements were phosphatidylethanolamines (PEs), and the minority were free fatty acids (FFAs), while phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) declined in pneumoconiosis. Clinical trans-omics analyses demonstrated that phenomes in pneumoconiosis connections with multiple lipids, which showed that pH, lung function, mediastinal lymph node calcification, and complication were highly correlated with lipid elements. Furthermore, up-regulated PE was corresponded to pH, smoking history and mediastinal lymph node calcification. PC was corresponded to dust exposure history, BMI and mediastinal lymph node calcification. We found altered lipid panels between male pneumoconiosis patients and healthy people by qualitatively and quantitatively measured plasma lipidomic profiles. The trans-omic analysis between clinical phenomes and lipidomes might have the potential to uncover the heterogeneity of lipid metabolism of pneumoconiosis patients and to screen out clinically significant phenome-based lipid panels.


Erythrosin 5'-isothiocyanate labels Cys549 as part of the low-affinity ATP binding site of Na+/K+-ATPase.
The high-affinity E1ATP site of Na+/K+-ATPase labeled with fluorescein 5'-isothiocyanate and its E2ATP site labeled with erythrosin 5'-isothiocyanate (ErITC), as was shown recently [Linnertz et al. (1998) J. Biol. Chem. 273, 28813-28821], reside on separate and adjacent catalytic alpha subunits. This paper provides evidence that specific labeling of the E2ATP binding site with ErITC resulted in a modification of the Cys549 residue in the tryptic fragment with the sequence Val545-Leu-Gly-Phe-Cys549-His550. Hence, Cys549 is part of or close to the low-affinity E2ATP binding site of Na+/K+-ATPase.


On farm production of arbuscular mycorrhizal fungi inoculum using lignocellulosic agrowastes.
The present study evaluated the efficiency of lignocellulosic agrowastes produced in Brazil as substrates for production of on farm AMF inoculum and tested different diluents and inoculation techniques. In a first experiment, Sorghum bicolor seedlings were colonized with Rhizophagus clarus or Claroideoglomus etunicatus and transplanted to 20 L bags containing sugarcane bagasse (SC), king palm leaf sheets (KP), or barley hulls (BH) mixed (1:1:1 or 2:1:1, v/v/v) with sand and rice shell. SC and KP were conducive for production of spores and infectious propagules. A number of infectious propagules obtained were greater than with BH and ranged from 233-350 propagules cm(-3) for both isolates in SC and KP at the1:1:1 mix dilution. Number of spores of both fungi was affected mainly by the SC agrowaste, and spore densities were significantly higher compared to KP and BH. In a second experiment, SC was mixed with soil or sand and inoculation consisted of transplanting colonized seedlings or adding soil inoculum. Number of propagules tended to differ for each fungus according to the inoculation technique or diluent. It is concluded from the data that SC and KP are suitable agrowastes to be incorporated in substrates for producing AMF inoculum using the on farm method.


Oral formulation of bendamustine hydrochloride for patients with advanced solid tumors; a phase 1 study.
To determine the maximum tolerated dose (MTD) and recommended dose (RD) of orally-administered bendamustine in Japanese patients with advanced solid tumors. The optimal dosing schedule, safety, pharmacokinetics, and preliminary antitumor effects were also evaluated. A multicenter, open-label trial with a standard 3 + 3 design and dose escalation by dose-limiting toxicity (DLT) was conducted. The treatment schedules were once daily for 7, 14, and 21 days every 3 weeks as one cycle. The total dose per cycle was increased from 175 to 840 mg/m2. Eighteen patients were enrolled in this study. DLT occurred in one of six patients at 75 mg/m2/day × 7 days, and one of three patients at 37.5 mg/m2/day × 14 days and 25 mg/m2/day × 21 days. However, the delayed recovery from a decrease in neutrophil or platelet count hampered the start of subsequent treatment cycles, and the trend was more prominent at 37.5 mg/m2/day × 14 days and 25 mg/m2/day × 21 days than in 75 mg/m2/day × 7 days. MTD was determined as 75 mg/m2/day × 7 days to allow acceptable hematologic recovery. The pharmacokinetics of orally-administered bendamustine were generally dose-dependent; however, the inter-individual variability is relatively large. The major adverse events were hematologic toxicities; gastrointestinal disorders were generally mild. Adverse drug reactions did not lead to the discontinuation of the drug. A partial response was observed in two of six patients (prostatic small cell carcinoma and thymic carcinoma) at 75 mg/m2/day × 7 days. The RD and optimal dosing schedule of orally-administered bendamustine was 75 mg/m2 once daily for 7 days every 3 weeks for the treatment of advanced solid tumors. (Trial registration number ClinicalTrials.gov NCT03604679. Registration date July 27, 2018).


Analysis of spatial and seasonal distributions of MODIS aerosol optical properties and ground-based measurements of mass concentrations in the Yellow Sea region in 2009.
Satellite-retrieved data on aerosol optical depth (AOD) and Ångström exponent (AE) using a moderate resolution imaging spectrometer (MODIS) were used to analyze large-scale distributions of atmospheric aerosols in East Asia. AOD was relatively high in March (0.44 ± 0.25) and low in September (0.24 ± 0.21) in the East Asian region in 2009. Sandstorms originating from the deserts and dry areas in northern China and Mongolia were transported on a massive scale during the springtime, thus contributing to the high AOD in East Asia. However, whereas PM10 with diameters ≤10 μm was the highest in February at Anmyon, Cheongwon, and Ulleung, located leeward about halfway through the Korean Peninsula, AOD rose to its highest in May. The growth of hygroscopic aerosols attendant on increases in relative humidity prior to the Asian monsoon season contributed to a high AOD level in May. AE typically appears at high levels (1.30 ± 0.37) in August due to anthropogenic aerosols originating from the industrial areas in eastern China, while AOD stays low in summer due to the removal process caused by rainfall. The linear correlation coefficients of the MODIS AOD and ground-based mass concentrations of PM10 at Anmyon, Cheongwon, and Ulleung were measured at 0.4~0.6. Four cases (6 days) of mineral dustfall from sandstorms and six cases (12 days) of anthropogenically polluted particles were observed in the central area of the Korean Peninsula in 2009. PM10 mass concentrations increased at both Anmyon and Cheongwon in the cases of mineral dustfall and anthropogenically polluted particles. Cases of dustfall from sandstorms and anthropogenic polluted particles, with increasing PM10 mass concentrations, showed higher AOD values in the Yellow Sea region.


Human pulmonary dirofilarial granuloma.
A case of pulmonary dirofilariasis in a human being is presented in which the lesion was visible roentgenographically for eighteen months prior to resection and in which the correct etiological diagnosis was made on frozen-section examination at the time of thoracotomy. The documented geographical spread of dirofilariasis in the canine population in the United States and southern Canada suggests that pulmonary dirofilariasis in human beings may be seen with increasing frequency by thoracic surgeons. The epidemiological and pathogenetic features of this unusual disease are discussed. A serological test for dirofilariasis is now available that may allow some patients to escape thoracotomy for this self-limited disorder.


Effects of Mg2+, Mn2+ and Ca2+ on adenylcyclase activity. Evidence for a metallic site.
In membrane preparations from immature erythrocytes from rats the effects of the divalent cations Mg2+, Mn2+ and Ca2+ on basal activity of adenylcyclase as well as on enzyme activity stimulated by isoprenaline (Ipn) or guanylyl-imidodiphosphate [Gpp(NH)p] were investigated.--Mn2+ is a ten-fold stronger activator of the enzyme than Mg2+ irrespective of the stimulant used. At suboptimal concentrations of the cations at all concentrations of Gpp(NH)p used (10(-6) to 10(-3) M) reaction velocities increase progressively over an incubation period of 40 min. Optimal cation concentrations, however, i.e. 3 x 10(-3) M Mn2+ and 3 x 10(-2)M Mg2+ elicit a constant and at 10(-4) M Gpp(NH)p maximal reaction velocity. In contrast, the Ipn-stimulated cAMP synthesis proceeds linearly at all Ipn concentrations used; a change of cation concentrations elicits only a change in reaction velocity, which is maximal at 10(-3) M Mn2+ and 10(-2) M Mg2+ respectively.--Ca2+ inhibits adenylcyclase activity in a non-competitive manner, irrespective of the stimulant and ion concentration used. The Mg2+-activated enzyme, however, is more susceptible to the inhibiting effect of Ca2+ than the Mn2+-activated enzyme.--It is concluded that Mn2+ and Mg2+ are allosteric effectors of the enzyme adenylcyclase, acting at a Me2+-site of the catalytic unit of adenylcyclase.


Impaired macroglial development and axonal conductivity contributes to the neuropathology of DYRK1A-related intellectual disability syndrome.
The correct development and activity of neurons and glial cells is necessary to establish proper brain connectivity. DYRK1A encodes a protein kinase involved in the neuropathology associated with Down syndrome that influences neurogenesis and the morphological differentiation of neurons. DYRK1A loss-of-function mutations in heterozygosity cause a well-recognizable syndrome of intellectual disability and autism spectrum disorder. In this study, we analysed the developmental trajectories of macroglial cells and the properties of the corpus callosum, the major white matter tract of the brain, in Dyrk1a+/- mice, a mouse model that recapitulates the main neurological features of DYRK1A syndrome. We found that Dyrk1a+/- haploinsufficient mutants present an increase in astrogliogenesis in the neocortex and a delay in the production of cortical oligodendrocyte progenitor cells and their progression along the oligodendroglial lineage. There were fewer myelinated axons in the corpus callosum of Dyrk1a+/- mice, axons that are thinner and with abnormal nodes of Ranvier. Moreover, action potential propagation along myelinated and unmyelinated callosal axons was slower in Dyrk1a+/- mutants. All these alterations are likely to affect neuronal circuit development and alter network synchronicity, influencing higher brain functions. These alterations highlight the relevance of glial cell abnormalities in neurodevelopmental disorders.


Static and fatigue mechanical characterizations of variable diameter fibers reinforced bone cement.
Fibers can be used to improve the mechanical properties of bone cement for the long-term stability of hip prostheses. However, debonding of the fibers from the matrix due to the poor fiber/matrix interface is a major failure mechanism for such fiber reinforced bone cements. In this study, a novel fiber (variable diameter fibers or VDFs) technology for reinforced bone cement was studied to overcome the interface problem of short-fiber composites. These fibers change their diameters along their length to improve the fiber/matrix interfacial bond by the mechanical interlock between the VDFs and the matrix. A novel composite made from novel ceramic VDFs incorporated in PMMA matrix was developed. Both static and fatigue tests were carried out on the composites. Conventional straight fiber (CSF) reinforced bone cement was also tested for comparison purposes. Results demonstrated that both the stiffness and the fatigue life of VDF reinforced bone cement are significantly improved (P < 0.05) compared with the unreinforced bone cement. VDF contents of 10% by volume increased the fatigue life over unreinforced bone cement by up to 100-fold. Also, the fatigue life and modulus of toughness of VDF reinforced cement were significantly greater than those of CSF reinforced cement (P < 0.05 and P < 0.001, respectively). Scanning electron microscopy (SEM) micrographs revealed that VDFs can bridge the matrix cracks effectively and pullout of VDFs results in much more extensive matrix damage than pullout of CSFs increasing the resistance to fatigue. Therefore, VDF reinforced cement was significantly tougher, having a greater energy dissipation capacity than CSF reinforced cement. VDFs added to bone cement could potentially avoid implant loosening due to the mantle fracture of bone cement and delay the need for revision surgery.


[Association of 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist gene with lumbar disc disease].
To investigate the association of 86 bp variable number tandem repeat (VNTR) polymorphism of interleukin-1 receptor antagonist (IL-1Ra) gene with lumbar disc disease and intervertebral disc degeneration. The 86 bp VNTR polymorphism of IL-1Ra gene was analyzed with PCR and electrophoresis for 81 patients with lumbar disc disease and 101 volunteers without sciatica (control). The grade of intervertebral disc degeneration was determined with magnetic resonance imaging, and the association of 86 bp VNTR polymorphisms with lumbar disc disease and intervertebral disc degeneration in those younger than 45 years was assessed. The presence of 86bp VNTR polymorphisms of IL-1Ra gene was detected in both patients with lumbar disc disease and the control subjects. The distribution of 86 bp VNTR polymorphisms of IL-1Ra gene showed no significant difference between the two groups, but the distributions of 1/1, 1/2 and 2/2 or 1, 2 genotypes differed significantly. The current data did not support a significant association between the distribution of IL-1Ra gene 86bp VNTR polymorphism and lumbar disc degeneration. IL-1Ra gene 86bp VNTR polymorphism is present among Chinese population in association with lumbar disc disease, but not with lumbar disc degeneration.


Quantitative Imaging of Morphometric and Metabolic Signatures Reveals Heterogeneity in Drug Response of Three-Dimensional Mammary Tumor Spheroids.
In order to monitor the drug responses of three-dimensional mammary tumor spheroids and to elucidate the role of inter- and intra-spheroid heterogeneity in determining drug sensitivity in the spheroids, an integrated image analysis framework was developed for morphometric and metabolic characterization of the three-dimensional tumor spheroids. Three-dimensional spheroid cultures of primary mammary tumor epithelial cells isolated from freshly excised tumors from a transgenic mouse model of adenocarcinoma (MMTV-PyMT) were imaged by using vital dyes and mitochondrial membrane potential markers. Custom-developed java and python program codes facilitated image processing, numerical computation, and graphical analysis of large datasets generated from the experiments. A panel of cancer drugs (rapamycin, BEZ235, MK2206, and flavopiridol) was tested to determine the degree of drug sensitivity as well as heterogeneity in drug response. A new quantitative metric (growth/toxicity) was developed based on morphometric parameters that were found to track the growth and apoptotic cell populations. Further, this study identified two parameters, namely, skew and kurtosis-which report the spatial heterogeneity in mitochondrial metabolism within the spheroids. The results of this study show that three-dimensional tumor spheroids selectively respond to cancer drugs depending on the specific metabolic pathways (AKT inhibition pathway in the present study), and there exists significant heterogeneity in the untreated tumor spheroids. Drug sensitivity of the spheroids was found to be associated with significant alterations in mitochondrial heterogeneity within the spheroids. In conclusion, the quantitative imaging of morphometric and metabolic analysis in large image datasets can serve as an excellent tool box for characterizing tumor heterogeneity in three-dimensional tumor spheroids and potentially, in intact tumors as well.


PCB1254 exposure contributes to the abnormalities of optomotor responses and influence of the photoreceptor cell development in zebrafish larvae.
Polychlorinated biphenyls (PCBs), a group of highly toxic environmental pollutants, have been report to influence the visual system development in children. However, the underlying mechanism is unclear. The study was aim to investigate the effects of continuous PCBs exposure on optomotor response (OMR) and retinal photoreceptor cell development-related gene expression in zebrafish larvae. The fertilized zebrafish embryos were exposed to PCBs at concentrations of 0.125, 0.25, 0.5, and 1mg/L until 7 days post-fertilization. Control groups with blank and 0.01% methanol were also prepared. OMR test was used to detect the visual behavior. The mRNA expression of the CRX, RHO, SWS1, and SWS2 was assessed by the Quantitative Real-Time PCR. The OMR test showed that the visual behavior of the larvae was most sensitive when the grating spatial frequency was 0.20LP/mm and the moving speed was 25cm/s. Moreover, the proportion of positively swimming fish was significantly reduced in the 0.5 and 1mg/L PCB1254 treatment group (P<0.05) compared with the controls. In addition, the expression of SWS2 was significantly down-regulated in all PCB1254 treatment groups (P<0.05), whereas the decreased expression of the CRX, RHO and SWS1 was found in the 0.5 and 1mg/L PCB1254 groups (P<0.05). This is the first report to demonstrate that continue exposure of zebrafish larvae to PCBs causes photoreceptor cell development-related gene expression changes that lead to OMR behavioral alterations. Analysis of these visual behavioral paradigms may be useful in predicting the adverse effects of toxicants on visual function in fish.


Epigenetic modifications of histones in cancer.
The epigenetic modifications of histones are versatile marks that are intimately connected to development and disease pathogenesis including human cancers. In this review, we will discuss the many different types of histone modifications and the biological processes with which they are involved. Specifically, we review the enzymatic machineries and modifications that are involved in cancer development and progression, and how to apply currently available small molecule inhibitors for histone modifiers as tool compounds to study the functional significance of histone modifications and their clinical implications.


Utility of the Pentax-AWS Airwayscope and Macintosh laryngoscope for airway management during chest compressions in 27° left-lateral tilt: a manikin simulation study of maternal cardiopulmonary resuscitation.
American Heart Association (AHA) 2010 cardiopulmonary resuscitation guidelines recommend high-quality chest compressions (minimum interruption, a pace >100 compressions/min, and a depth more than 5 cm). They propose minor changes for pregnant women: manual left deviation of the uterus or a left-lateral incline of 27°-30° to alleviate pressure on the inferior vena cava. We examined the performance of the Pentax-AWS Airwayscope (AWS) and Macintosh laryngoscope (McL) for airway management during chest compressions on a 27° left-lateral tilt (27 LLT) operating table. The study included 18 novice doctors in our anesthesia department. They performed tracheal intubation on a manikin positioned on a 27 LLT operating table using the AWS or McL with or without chest compressions. We measured the intubation time and success rate for tracheal intubation. Intubation success rate with the McL decreased with chest compressions compared to without chest compressions (12/18 vs. 18/18, P < 0.05). Intubation time with the McL was lengthened with chest compressions compared to without chest compressions (18.9 ± 4.0 s vs. 11.1 ± 1.0 s, P < 0.05). Intubation success rate was the same for the AWS with and without chest compressions (18/18 in both cases), and intubation time did not increase significantly without compressions compared to with compressions (11.6 ± 1.4 s vs. 12.6 ± 1.2 s, NS). The AWS is an effective tool for airway management during chest compressions in 27 LLT in a manikin, suggesting that the AWS may be a useful device for airway management during maternal resuscitation.


Randomised crossover studies of the bioequivalence of two fenofibrate formulations after administration of a single oral dose in healthy volunteers.
Bioequivalence of a newly developed semi-solid formulation (Lidose) of fenofibrate (CAS 49562-28-9), and a reference, micronized formulation of fenofibrate was investigated in two randomised, open-label clinical studies with a crossover design. Both studies involved two distinct groups of 24 healthy volunteers. Doses of 67 mg and 200 mg, respectively, were used in study 1 and study 2. On day 1, a single oral dose was administered to all subjects, using one of the two formulations to be compared. Single oral dosing with the other formulation occurred after a washout period of at least 8 days. Blood samples were taken after each dosing for measurement of plasma fenofibric acid concentrations by high-performance liquid chromatography (HPLC) combined with fluorescence detection, and plasma pharmacokinetic parameters were determined. No statistically significant differences were noted for Cmax, Tmax, AUC0-t and AUC0-variation of between subjects treated with the new formulation and those receiving the reference formulation. Side effects were mild and not significantly different between the two fenofibrate preparations. These two studies based on validated methods demonstrate that the new and the reference fenofibrate formulations are bioequivalent when administered at the two doses studied.


Two New Cytoarchitectonic Areas on the Human Mid-Fusiform Gyrus.
Areas of the fusiform gyrus (FG) within human ventral temporal cortex (VTC) process high-level visual information associated with faces, limbs, words, and places. Since classical cytoarchitectonic maps do not adequately reflect the functional and structural heterogeneity of the VTC, we studied the cytoarchitectonic segregation in a region, which is rostral to the recently identified cytoarchitectonic areas FG1 and FG2. Using an observer-independent and statistically testable parcellation method, we identify 2 new areas, FG3 and FG4, in 10 human postmortem brains on the mid-FG. The mid-fusiform sulcus reliably identifies the cytoarchitectonic transition between FG3 and FG4. We registered these cytoarchitectonic areas to the common reference space of the single-subject Montreal Neurological Institute (MNI) template and generated probability maps, which reflect the intersubject variability of both areas. Future studies can relate in vivo neuroimaging data with these microscopically defined cortical areas to functional parcellations. We discuss these results in the context of both large-scale functional maps and fine-scale functional clusters that have been identified within the human VTC. We propose that our observer-independent cytoarchitectonic parcellation of the FG better explains the functional heterogeneity of the FG compared with the homogeneity of classic cytoarchitectonic maps.


Fecundability in relation to use of fertility awareness indicators in a North American preconception cohort study.
To quantify the frequency of use of selected fertility awareness indicators and to assess their influence on fecundability. Web-based prospective cohort study. Not applicable. Female pregnancy planners, aged 21-45 years, attempting conception for ≤6 cycles at study entry. None. We ascertained time to pregnancy, in menstrual cycles, with bimonthly questionnaires. We estimated adjusted fecundability ratios (FRs) and confidence intervals (CIs) using proportional probabilities models, controlling for age, income, education, smoking, intercourse frequency, and other lifestyle and reproductive factors. A total of 5,688 women were analyzed, with a mean age of 29.9 years and mean time trying of 2.1 cycles at baseline; 30% had ever been pregnant. At baseline, 75% were using one or more fertility indicators (counting days or charting menstrual cycles [71%], measuring basal body temperature [BBT, 21%], monitoring cervical fluid [39%], using urine LH tests [32%], or feeling for changes in position of the cervix [12%]). Women using any fertility indicator at baseline had higher subsequent fecundability (adjusted FR 1.25, 95% CI 1.16-1.35) than those not using any fertility indicators. For each individual indicator, adjusted FRs ranged from 1.28-1.36, where 1.00 would indicate no relation with fecundability. The adjusted FR for women using a combination of charting days, cervical fluid, and urine LH was 1.48 (95% CI 1.31-1.67) relative to women using no fertility indicators. In a North American preconception cohort study, use of fertility indicators indicating the fertile window was common, and was associated with greater fecundability.


Hierarchical assembly of SnO2 nanorod arrays on alpha-Fe2O3 nanotubes: a case of interfacial lattice compatibility.
SnO2 nanorod arrays were hierarchically assembled onto the surface of alpha-Fe2O3 nanotubes via a facile solution method. Determined by the hexagonal geometrical nature of the alpha-Fe2O3 nanotubes, the heterostructures were of 6-fold symmetry. HRTEM characterizations demonstrated that the lattice mismatch at the interface was an important factor in determining the growth direction of the secondary nanorod arrays.


Systematic classification of alleles of the glycophorin A (MN blood group) gene.
Ten alleles (five M and five N alleles) of the MN blood group system with normal antigenicity were found by sequencing the glycophorin A (GPA) gene. This study demonstrates the systematic classification of these alleles to major or minor variations of the standard alleles. GPA-specific fragments ranging from 150 to 3.8 kb in length were amplified from the templates, and exons 1-7 and introns 1-6 were sequenced. The data were analyzed phylogenetically to classify these alleles into major groups or clusters. The ten alleles were grouped into four major clusters M10X (M101-M103), M20X (M201 and M202), N10X (N101-N104) and N20X (N201), where 'X' represents a digit indicating minor variations. This grouping was supported by phylogenetic analysis. The cluster system of GPA alleles is highly informative for genetic screening.


Determination of total proton release in purple membrane suspension by umbelliferone fluorescence quenching technique.
A technique for determining total proton release from purple membrane suspension under steady illumination has been described. Illuminated purple membrane is found to quench the fluorescence life-time of umbelliferone indicating the release of protons in the medium. Besides the "stoichiometric" release of protons from bacteriorhodopsin, there seems to be release of protons from sources other than protonated retinylidene Schiff base moiety also.


Time course and substance P effects on the vascular and morphological changes in adjuvant-induced monoarthritic rats.
The aim of this study is to characterize the time course of the vascular and morphological changes in arthritic rat knee joints induced by Freund's complete adjuvant (FCA), and to investigate the effects of substance P on these changes. Single unilateral intra-articular injections of 0.1 ml FCA produced swelling of the ipsilateral knees for 4 weeks, blood vessel permeability was increased for 1 week, but blood flow was unaffected except for minor bilateral increases on day 28. The ipsilateral knees also showed marked accumulation of immune cells from day 3 to day 28, minor synovial tissue proliferation on week 2, and some cartilage erosions on weeks 1 and 2. Another group of rats was given additional injection of 1 nmol substance P in their adjuvant-treated knees at 4 h prior to assessments of inflammatory parameters on each specified day. This produced further swelling in their ipsilateral knees on day 3 and day 14, blood vessel permeability was augmented in the first 2 weeks, and blood flow was increased throughout the 4 weeks except on day 7. Parallel but smaller increases in vascular permeability and blood flow were also observed in their contralateral knees. Substance P did not affect FCA-induced changes in immune cell infiltration, synovial tissue proliferation, and cartilage erosion. These findings confirm that intra-articular injection of a low dose of FCA could elicit discrete monoarthritis in rat knees, and substance P could exacerbate and spread the early signs of this disease to the contralateral knees.


[Cloning and characterization of mitochondrial NADH dehydrogenase gene of Cysticercus cellulosae].
To clone and characterize the NADH1 gene of Cysticercus cellulosae. A cDNA library was constructed from Cysticercus cellulosae and was immunoscreened by using rabbit anti-Cysticercus cellulosae polyclonal antibody. The gene structure and its possible function were analyzed by comparing with sequences available in the GenBank, after the insert of positive clone was subcloned and the nucleotide sequence of the insert was determined by dideoxynucleotide chain termination method. A cDNA clone (named TS5) with a length of 1,082 bp was isolated. The 5' terminal of cloned gene contained one open reading frame of 1-578 bp encoding 192 amino acid residues of mitochondrial NADH dehydrogenase subunit 1 and the 3' terminal contained three kinds of tRNA genes.


Mitral valve dysplasia characterized by isolated cleft of the anterior leaflet resulting in fixed left ventricular outflow tract obstruction.
A 7-month-old, sexually intact male English toy spaniel weighing 4 kg was referred for evaluation of a subclinical cardiac murmur. Echocardiography disclosed fixed left ventricular outflow tract obstruction that was caused by attachment of a cleft anterior mitral valve leaflet to the interventricular septum. Neither atrial nor ventricular septal defects were detected. Fixed obstruction of the left ventricular outflow tract by a malformed mitral valve is rare in human beings and has not been previously reported in the dog.


Flavoxate hydrochloride for urinary urgency after pelvic radiotherapy: comparison of 600 mg versus 1200 mg daily dosages.
This preliminary communication reports on a non-randomized pilot type trial of 34 females with urgency after pelvic radiotherapy who were treated with flavoxate hydrochloride for 4 weeks. A dosage of 600 mg/day was given to 21 patients and 1200 mg/day to 13 patients. Clinically, both regimens achieved comparable results. Urodynamically (first desire volume, bladder capacity and pressure at capacity) treatment with 1200 mg/day was significantly superior to 600 mg/day. Both schedules were equally well tolerated by patients and no treatment interruption occurred. A randomized double-blind trial comparing 600 and 1200 mg/day flavoxate hydrochloride is currently underway the results of which will be reported in due course.


Using Crowdfunding Campaigns to Examine Financial Toxicity and Logistical Burdens Facing Families of Children With Wilms Tumor.
Treatment for pediatric solid tumors is often intense and multidisciplinary and can create a substantial financial burden for families. Assessing these burdens, termed the financial toxicity of treatment, can be difficult. Using Wilms tumor as an example, we evaluated crowdfunding campaigns in an attempt to better understand the impact of economic and logistic challenges associated with pediatric solid tumor care and identify features associated with successful fundraising with this method. We used a webscraping algorithm to identify crowdfunding campaigns on GoFundMe.com for pediatric patients with Wilms tumor in the United States. We conducted a cross-sectional analysis to describe the patients and families seeking crowdfunding support for cancer care. After fundraizing information was extracted using the webscraping algorithm, each fundraiser was verified and examined by two independent reviewers to assess demographic, qualitative, disease, and treatment variables. Successful fundraisers, defined as those meeting stated financial goals, were compared to unsuccessful campaigns to identify variables associated with successful crowdfunding campaigns. We identified 603 children with Wilms tumor and an associated crowdfunding campaign. The median age was 4 y. The majority lived in two-parent households (68.5%). Patients mentioned siblings in 35.5% of fundraisers. While motivations for crowdfunding varied, hardships endured by families included loss of employment (52.2%), need for childcare for other children (9.8%), direct costs of care [co-payments, insurance, pharmaceuticals, out-of-pocket care costs, etc.] (80.9%), indirect costs associated with seeking care [transportation, parking, lodging, lost opportunity cost, etc.] (56.2%), and need for relocation to pursue complex cancer care (6.8%). Disease characteristics in this cohort were limited to self-reports by families. However, fundraisers mentioned disease characteristics, including tumor stage (47.6%), size (11.4%), positive nodal status (9.6%), metastatic disease (3.6%), pathology (11.8%), upstaging (4.6%), and disease recurrence (8.6%). No individually examined demographic, support, disease, or hardship-related factors varied significantly between successful and unsuccessful crowdfunding campaigns (all P > 0.05). However, successful campaigns requested less money ($11,783.25 successful versus $22,442.2 unsuccessful, <0.001), received more money ($16,409.5 successful vs 7427.4 unsuccessful, P < 0.001), and solicited larger donor numbers (170.3 successful versus 86.3 unsuccessful, P < 0.001). Families whose children undergo multimodal cancer care have significant expenses and burdens and can use crowdfunding to support their costs. Careful consideration of the financial and logistic strains associated with pediatric solid tumor treatment, including thorough analysis of crowdfunding sites, may support better understanding of nonclinical burdens, supporting therapeutic relationships and patient outcomes.


Conservative management of Bowen's disease of the anus.
Bowen's disease of the anus is usually treated by wide local excision including macroscopic normal areas if random biopsies show dysplasia. Skin grafting will often be necessary, since areas of microscopic dysplasia may be found at a considerable distance from the gross affected site. In this study of 11 patients with Bowen's disease of the anus we report the results of a more conservative approach. All patients were treated by local excision of the gross affected areas only, and none of the patients required skin grafting. Seven patients were followed for a median of 34 months without macroscopic recurrence, including 3 patients with histologically proven dysplasia in the resection margins. Two patients, one with and one without dysplasia in the resection margins, developed recurrence within a year. One patient with an area of invasive carcinoma was first treated by local excision, but required an abdominoperineal excision 3 months later. One patient lost to follow-up had invasive carcinoma after 3 years. It is concluded that a conservative surgical approach in Bowen's disease of the anus is justified, provided the patients are followed closely.


Limited Impact of Delta Variant's Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population.
The SARS-CoV-2 pandemic has impacted public health systems all over the world. The Delta variant seems to possess enhanced transmissibility, but no clear evidence suggests it has increased virulence. Our data show that pre-exposed individuals had similar neutralizing activity against the authentic COVID-19 strain and the Delta and Epsilon variants. After only one vaccine dose, the neutralization capacity expanded to all tested variants in pre-exposed individuals. Healthy vaccinated individuals showed a limited breadth of neutralization. One vaccine dose did induce similar neutralizing antibodies against the Delta as against the authentic strain. However, even after two doses, this capacity only expanded to the Epsilon variant.


Mobile phones, radiofrequency fields, and health effects in children--epidemiological studies.
In 2004, when WHO organized a workshop on children's sensitivity to electromagnetic fields, very few studies on radiofrequency fields were available. With the recent increase in mobile phone use among children and adolescents, WHO has identified studies on health effects in this age-group as a high priority research area. There are no empirical data supporting the notion that children and adolescents are more susceptible to RF exposure, but the number of studies is still relatively small. There are a few cross-sectional studies on well-being, cognitive effects and behavioral problems, and some cohort studies, mainly of maternal use of mobile phones during pregnancy. Cancer outcomes have been studied in relation to environmental RF exposure, e.g. from transmitters, and only one study on mobile phone use in children and adolescents and brain tumor risk has been published. Several methodological limitations need to be taken into consideration when interpreting the findings of the epidemiological studies. The cross-sectional design does not allow determination of the temporal sequence of exposure and outcome, and for several outcomes there is a large potential for reversed causality, i.e. that the outcome causes an increased RF exposure rather than the opposite. Biases such as recall errors in self-reported mobile phone use, lack of confounding control, e.g. of other aspects of mobile phone use than RF fields, trained behaviors, and pubertal development, makes causal interpretations impossible. Future studies need to include prospectively collected exposure information, incident outcomes, and proper confounding control. Monitoring of brain tumor incidence trends is strongly recommended.


Relationship between suicide, homicide and accidental deaths among the aged in Finland in 1951-1979.
Time trends for suicide, homicide and accident mortality among the Finnish population 65 years or over in 1951-1979 are presented. From 1951 to 1967 suicide, motor-vehicle accident mortality and overall accident mortality among elderly males tended to follow more or less similar patterns. In 1951-1979 male suicide rates correlated positively and significantly over time with male motor-vehicle accident mortality and with male total accident mortality. The results from this mortality analysis in the elderly population are compared with those obtained by Holinger et al. in the total population. There is also a brief discussion of the methodological problems of the study. The results suggest that self-destructive tendencies are not a central variable in female accident mortality among the aged population. On the other hand, it is possible that they play some role in motor-vehicle accident mortality in the aged male population. No suggestions about self-destructive tendencies in homicides among the aged could be made.


Electroencephalogram processing using neural networks.
The electroencephalogram (EEG), a highly complex signal, is one of the most common sources of information used to study brain function and neurological disorders. More than 100 current neural network applications dedicated to EEG processing are presented. Works are categorized according to their objective (sleep analysis, monitoring anesthesia depth, brain-computer interface, EEG artifact detection, EEG source-based localization, etc.). Each application involves a specific approach (long-term analysis or short-term EEG segment analysis, real-time or time delayed processing, single or multiple EEG-channel analysis, etc.), for which neural networks were generally successful. The promising performances observed are demonstrative of the efficiency and efficacy of systems developed. This review can aid researchers, clinicians and implementors to understand up-to-date interest in neural network tools for EEG processing. The extended bibliography provides a database to assist in possible new concepts and idea development.


Internet resources for veterinary toxicologists.
The informational needs of veterinary toxicologists are diverse due to their involvement in clinical, research and regulatory toxicology. The internet provides an important tool for assessing a wide array of useful toxicologic information that is otherwise not readily available. Internet resources utilized by veterinary toxicologists include governmental, commercial, academic and non-profit websites.


Lead removal by polyacrylamide-bentonite and zeolite composites: effect of phytic acid immobilization.
Polyacrylamide (PAA)-bentonite (B) and zeolite (Z) composites were prepared by direct polymerization of PAA in suspensions of B and Z. Phytate (Phy) immobilized onto the composites to obtain their Phy modifications. FT-IR and XRD were employed to characterize their structures. The sorption of Pb(2+) from various adsorption media onto the composites was then investigated. The reusability and storage characteristics of the adsorbents with and without Phy were also considered for Pb(2+) adsorption. All isotherms were L and H type of the Giles classification. The Phy adsorption capacities (X(M)) of PAA-B and Z lower than those of bare B and Z due to their surface coverage by PAA. The Phy modification decreased the Pb(2+) adsorption capacities of B and PAA-B but ascended those of Z and PAA-Z. However, Phy significantly increased the Langmuir equilibrium constants (K(L)) for all adsorbents. Ionic strength of the adsorption media was favorable for the adsorption capacity of PAA-B while not for that of PAA-Z. The chemical structure of the composites was not changed after five reuses and the storage foregoing. It is foreseen that the use of PAA-B and PAA-Z and their Phy modifications will provide practicality and effectiveness for Pb(2+) separation and removal procedures. The X(M) (mol kg(-1)) and K(L) (L mol(-1)) values for Pb(2+) adsorption from a model solution were 0.16 and 3625 for PAA-B, 0.18 and 5.1 x 10(5) for PAA-B-Phy, 0.28 and 13210 for PAA-Z and 1.65 and 2.0 x 10(5) for PAA-Z-Phy.


Array-MAPH: a methodology for the detection of locus copy-number changes in complex genomes.
High-throughput genome-wide screening methods to detect subtle genomic imbalances are extremely important for diagnostic genetics and genomics. Here, we provide a detailed protocol for a microarray-based technique, applying the principle of multiplex amplifiable probe hybridization (MAPH). Methodology and software have been developed for designing unique PCR-amplifiable sequences (400-600 bp) covering any genomic region of interest. These sequences are amplified, cloned and spotted onto arrays (targets). A mixture of the same sequences (probes) is hybridized to genomic DNA immobilized on a membrane. Bound probes are recovered and quantitatively amplified by PCR, labeled and hybridized to the array. The procedure can be completed in 4-5 working days, excluding microarray preparation. Unlike array-comparative genomic hybridization (array-CGH), test DNA of specifically reduced complexity is hybridized to an array of identical small amplifiable target sequences, resulting in increased hybridization specificity and higher potential for increasing resolution. Array-MAPH can be used for detection of small-scale copy-number changes in complex genomes, leading to genotype-phenotype correlations and the discovery of new genes.


The role of the individual TOM subunits in the association of PINK1 with depolarized mitochondria.
Mitochondria dysfunction is involved in the pathomechanism of many illnesses including Parkinson's disease. PINK1, which is mutated in some cases of familial Parkinsonism, is a key component in the degradation of damaged mitochondria by mitophagy. The accumulation of PINK1 on the mitochondrial outer membrane (MOM) of compromised organelles is crucial for the induction of mitophagy, but the molecular mechanism of this process is still unresolved. Here, we investigate the association of PINK1 with the TOM complex. We demonstrate that PINK1 heavily relies on the import receptor TOM70 for its association with mitochondria and directly interacts with this receptor. The structural protein TOM7 appears to play only a moderate role in PINK1 association with the TOM complex, probably due to its role in stabilizing this complex. PINK1 requires the TOM40 pore lumen for its stable interaction with the TOM complex and apparently remains there during its further association with the MOM. Overall, this study provides new insights on the role of the individual TOM subunits in the association of PINK1 with the MOM of depolarized mitochondria. KEY MESSAGES: TOM70 is the main receptor for the import of PINK1 into mitochondria. TOM20 plays only a minor role in PINK1 recognition at the organellar outer membrane. PINK1 association with the TOM complex is reduced upon knock-down of TOM7. The lumen of the TOM pore is crucial for PINK1 association with the outer membrane. TcPINK1 blocks the TOM pore in depolarized mitochondria.


Forniceal rupture secondary to ureterocele and increased urine flow.
A case of a simple ureterocele presenting with spontaneous forniceal rupture is described. Rupture followed hypophysectomy for Cushing's disease and high urine outflow. This presentation has not been reported previously.


Treating fluid noncompliance in the hemodialysis population using unit wide contests.
Our dialysis unit observed fluid noncompliance over a wide variety of patients. The consequences of fluid abuse that can include systemic and cardiovascular overload are a frequent clinic complication of hemodialysis patients. In spite of all our attempts, our dialysis unit continued to have a substantial group of patients who could not adhere to their fluid restriction. Our dialysis unit needed a novel program to help motivate patients to comply with diet/medication fluid regimens. A method that seems to work well in our dialysis unit is playing unit-wide games. We developed "The Fluid Game," an original patient education idea, for providing renal patients with a fun incentive to keep their interdialytic weight gains within acceptable limits.


[Effect of dibazol on the state of the hypophyseal-adrenal system in patients operated on under thiopental anesthesia].
In the observations over the patients subjected to operations on the limbs under thiopental narcosis and in the experiments on white rats exposed to a shockogenic trauma (by Kennon's method) it has been found that the prophylactic injection of 1--2 mg/kg dose of dibazol rises the non-specific resistance of the body. The hormones of the pituitary-adrenal system have been found to hold an important place in the mechanism of the effect of dibazol.


Cerebral ischemia in gerbils: improvement of survival after postischemic treatment with oligo-prostaglandin B.
Gerbils were subjected to bilateral carotid artery occlusion for either 15 or 20 min. After ischemia the animals were injected i.p. with oligo-prostaglandin B (oligo-PGB; trimer of 16,16'-dimethyl-15-dehydro-prostaglandin B1) dissolved in 4% sodium-bicarbonate, or with the vehicle. The dosing regimen of oligo-PGB was 0.5, 1, 2, 5, 10 mg/kg injected 5 min postischemia, or 1 mg/kg injected 30, 60, 90, 120 min after ischemia, or 10 mg/kg injected 5 min and 24 h postischemia. Behaviour of the animals and their mortality were studied for 14 days after ischemia. Administration of the drug did not affect recovery of the electrical activity in the brain and did not reduce the number of postischemic seizures. Following 15 min ischemia, administration of oligo-PGB resulted in statistically valid improvement of survival (P less than 0.04 or better) in all treatment groups. After 20 min ischemia only the double injection (10 mg/kg at 5 min and 24 h postischemia) resulted in a substantial survival improvement (64%, P less than 0.005). The mechanism of the drug action is unknown but, based on the available data, the authors believe it to be related to the modification of arachidonic acid metabolism in the late postischemic period.


A nondestructive solution to quantify monosaccharides by ATR-FTIR and multivariate regressions: A case study of Atractylodes polysaccharides.
The quality evaluation of nature polysaccharides is a tough nut to crack because of its high Mw distributions and larger polarity property. It is well-known that infrared spectroscopy and multiple regression modeling have been used for quantitative examinations in multiple fields, but it has not been applied to the compositional analysis of polysaccharides. In this study, attenuated total reflectance-fourier transform infrared spectroscopy is used to simultaneously quantify aldoses, ketose and uronic acids in Atractylodes polysaccharides by a combination of multivariate regressions. After experience of different data processing pretreatments, the resulting spectrum contains maximum amount of information of monosaccharide contents in Atractylodes polysaccharides. In this case, different smoothing points, derivatives, SNV and MSC are used in the pre-modeling spectrum processing and VIP screening is used to reduce the number of variables to simplify the calculation of the model. All the most optimal prediction models have both good prediction ability (R2 ≥ 0.9 and RPD > 3) and no over fitting (RMSEP/RMSEC < 3). This strategy has opened a new possibility for the nondestructive determination of complex monosaccharide compositions of natural polysaccharides in a short detection time, low equipment requirement and high experimental safety.


Color development time of the Lowry protein assay.
Color development of the Lowry protein assay was tracked over time for bovine serum albumin (BSA) concentrations ranging from 40 to 600 microg/ml. The time interval between 2 and 4h produced the most stable readings. This time frame also improved linearity of the standard curve.


Salmonella spp. on pork at cutting plants and at the retail level and the influence of particular risk factors.
This article describes the contamination of pork with Salmonella spp. in cutting plants and butchers' shops in The Netherlands and quantifies the influence of several risk factors. When contaminated carcasses are being processed, the main risk factors regarding cross contamination are inapt cleaning and disinfection (OR 12.8), manipulation of contaminated materials as such (OR 4.7) and (re)contaminated surfaces (OR 4.4). However, in the current situation, where contaminated carcasses are constantly being brought into cutting lines, interim cleaning and disinfection of surfaces and utensils during breaks and at the end of the working day will most likely prevent not more than about 10% of all cross contamination that takes place during a working day. Thus, as long as contaminated carcasses are being processed, about 90% of the cross contamination that occurs in cutting plants is practically unavoidable. It can therefore also be concluded that under these circumstances the implementation of codes of good manufacturing practices (GMP) and Hazard Analysis Critical Control Point (HACCP)-inspired production methods will only be marginally effective in the control of Salmonella spp. cross contamination in cutting lines. The same is more or less true for the processing of contaminated cuts or carcasses by butchers in shops and supermarkets. Furthermore, in contrast to the situation in cutting plants, it may be that up to 10% of butcher's shops or kitchens of restaurants become colonized for several weeks or months with their own endemic 'house flora' of Salmonella spp., which are originally introduced via the purchased contaminated products of animal origin. Though there are no hard data to substantiate this, it can be suspected that these shops and restaurants represent the more badly managed, i.e. poorly cleaned and disinfected, enterprises. However, several analytical limitations hinder an exact determination of the prevalence of Salmonella spp. contaminated pork and an exact quantification the influence of risk factors. The diagnostic value (i.e. the sensitivity, specificity, precision and predictive value) of the combination of swabbing of carcasses and cuts and the usually employed culturing methods, in particular, is largely unknown, and there are indications that it may be seriously questioned. Without a more thorough knowledge about the diagnostic value of current and future methods of sampling and identification, it is impossible to provide for more accurate estimations of the prevalence of Salmonella positive carcasses and cuts. Based on the research data, the incidence of contaminated cuts and retail-ready pork can not be estimated more precise than as somewhere between 5-40%. When compensating for the discussed methodological flaws, it must be assumed that currently the true prevalence of contaminated primal cuts and retail-ready pork in butchers' shops is about 25-30%, and that of minced pork and pork sausages about 50-55%. Lastly it is concluded that if carcasses were Salmonella-free, consumers could in principle be provided with virtually Salmonella-free pork. It is therefore recommended that the EU allows for a decontamination step in slaughterhouses with a substance that is generally recognized as safe, provided that the producers strictly adhere to GMP-principles.


The ethanol-soluble part of a hot-water extract from Artemisia iwayomogi inhibits liver fibrosis induced by carbon tetrachloride in rats.
This study was carried out to investigate the protective effects of the hot-water extract from Artemisia iwayomogi (Compositae) on carbon tetrachloride-induced liver fibrosis in rats. Liver injury was induced by oral administration of carbon tetrachloride (1 mL kg(-1)) twice a week during 4 weeks of A. iwayomogi treatment. Extracts from A. iwayomogi were prepared and administered to rats orally (2 g kg(-1) as A. iwayomogi for 4 weeks) as follows: group 1, hot-water extract; group 2, ethanol-soluble part of hot-water extract; group 3, ethanol-insoluble part of hot-water extract; and group 4, methanol extract. In rats treated with the ethanol-soluble part of the hot-water extract, liver hydroxyproline content was reduced to 74% that of carbon tetrachloride control rats (P < 0.05). Protein expression of alpha smooth muscle cell like actin was also decreased in rats treated with the ethanol-soluble part of the hot-water extract, which indicates inhibition of hepatic stellate cell activation. Liver malondialdehyde levels were significantly lowered in rats treated with the ethanol-soluble part of hot-water extract (P < 0.05). Serum cholesterol levels in rats treated with hot-water extract, ethanol-soluble or -insoluble parts of hot-water extract or methanol extract were significantly reduced when compared with those of carbon tetrachloride control rats (P < 0.05). The ethanol-soluble part of the hot-water extract from A. iwayomogi inhibited fibrosis and lipid peroxidation in rats with liver fibrosis induced by carbon tetrachloride. Both hot-water extract (either ethanol-soluble or -insoluble) and methanol extract of A. iwayomogi also lowered serum cholesterol levels in fibrotic rats.


Exploring the Impact of the COVID-19 Pandemic on Employees' Workplace Health Promotion Preferences.
The COVID-19 pandemic has led to profound changes in the workplace as well as increases in stress, missed preventive care, and other health concerns. There is limited research since the onset of the pandemic on employees' primary health concerns and their willingness to engage with workplace health promotion (WHP) programs to address these needs. We conducted this survey about employees' current health priorities as a first step to exploring whether WHP programs need to evolve to be responsive to employees' needs at this stage of the pandemic. National cross-sectional survey. United States, April 29-May 5, 2022. 2053 Americans employed part or full time. 17-item online survey assessing demographics, health priorities, and impact of the pandemic on health. Descriptive statistics, SPSS Version 19. Employees' most common health concerns included work/life balance and stress (each cited by 55%). Nearly half (46%) said their health or well-being was affected by the pandemic; within this group, the most common concerns were stress (66%), anxiety (61%), sleep (49%), and depression (48%). Almost all (94%) indicated they would be open to receiving support from their employers. This research is a first step in learning about employees' current health priorities and how they may have changed. WHP researchers and practitioners can determine how their programs align with current priorities. Our future research will explore employees' preferences, heath behaviors, and their current workplace environments in more depth.


Simultaneous anterior and posterior serosal mapping of gastric slow-wave dysrhythmias induced by vasopressin.
What is the central question of this study? This study aimed to provide the first comparison of simultaneous high-resolution mapping of anterior and posterior gastric serosa over sustained periods. What is the main finding and its importance? Episodes of spontaneous gastric slow-wave dysrhythmias increased significantly following intravenous infusion of vasopressin compared with the baseline state. A number of persistent dysrhythmias were defined, including ectopic activation, conduction block, rotor, retrograde and collision/merger of wavefronts. Slow-wave dysrhythmias could occur either simultaneously or independently on the anterior and posterior gastric serosa, and interacted depending on activation-repolarization and frequency dynamics. High-resolution mapping enables mechanistic insights into gastric slow-wave dysrhythmias and is now achieving clinical translation. However, previous studies have focused mainly on dysrhythmias occurring on the anterior gastric wall. The present study simultaneously mapped the anterior and posterior gastric serosa during episodes of dysrhythmias induced by vasopressin to aid understanding of dysrhythmia initiation, maintenance and termination. High-resolution mapping (8 × 16 electrodes on each serosa; 20-74 cm2 ) was performed in anaesthetized dogs. Baseline recordings (21 ± 8 min) were followed by intravenous infusion of vasopressin (0.1-0.5 IU ml-1 at 60-190 ml h-1 ) and further recordings (22 ± 13 min). Slow-wave activation maps, amplitudes, velocity, interval and frequency were calculated, and differences compared between baseline and postinfusion. All dogs demonstrated an increased prevalence of dysrhythmic events following infusion of vasopressin (17 versus 51%). Both amplitude and velocity demonstrated significant differences (baseline versus postinfusion: 3.6 versus 2.2 mV; 7.7 versus 6.5 mm s-1 ; P < 0.05 for both). Dysrhythmias occurred simultaneously or independently on the anterior and posterior serosa, and then interacted according to frequency dynamics. A number of persistent dysrhythmias were compared, including the following: ectopic activation (n = 2 animals), conduction block (n = 1), rotor (n = 2), retrograde (n = 3) and collision/merger of wavefronts (n = 2). We conclude that infusion of vasopressin induces gastric dysrhythmias, which occur across a heterogeneous range of frequencies and patterns. The results demonstrate that different classes of gastric dysrhythmias may arise simultaneously or independently in one or both surfaces of the serosa, then interact according to their relative frequencies. These results will help to inform interpretation of clinical dysrhythmia.


Hormonal organization and activation: evolutionary implications and questions.
Comparative endocrinology is a fascinating field of science in part because it addresses both ultimate and proximate causation. Research on sexual dimorphism and sexual differentiation has excellent potential for this kind of integration. Vertebrate comparative endocrinologists have made many important discoveries about the role of genes and sex steroid hormones in the organization and activation of sexually differentiated behavior, brain function, anatomy and physiology. In addition to taxonomically general principles and conserved features, there is also striking diversity in sexual differentiation processes. Much of the evolutionary basis of this diversity (its phylogenetic history and adaptive functions) is not well understood. A set of questions is raised to illustrate this point, with an emphasis on mechanisms of sexual dimorphism in body size and ornamentation, sexual differentiation of avian behavior, particularly in Japanese quail and zebra finches, and the puzzle of the phylogenetic distribution of vertebrate sex determining mechanisms. Applying a comparative approach grounded in established phylogenies and concepts from evolutionary developmental biology such as developmental modules holds promise for generating and testing new hypotheses and eventually answering some of these questions.


Optimization of in vitro measurement of proteasome activity in mammalian cells using fluorogenic substrates.
The proteasome is the major multi-catalytic machinery responsible for protein degradation and maintenance of the proteome. The 26S proteasome is an ATP-dependent proteolytic complex, dedicated to the degradation of poly-ubiquitinated proteins. It consists of a 20S proteolytic core and one or two flanking 19S regulatory complexes. The three catalytic subunits harboring chymotrypsin-like (CT-L), trypsin-like (T-L), and caspase-like (C-L; also termed PGPH) activities respectively reside in the 20S proteasome that can also exist in a free form and degrade oxidized and unfolded proteins. Impaired proteasome function has been implicated in the pathogenesis of a number of diseases including Alzheimer's disease, diabetes, cancer and aging. The emerging interest in proteasome function as diagnostic marker of various human pathologies and therapeutic target necessitates the development of accurate, sensitive and reliable methodologies for the assessment of proteasome activity. Herein, we describe an optimization procedure for the measurement of CT-L, T-L and C-L activities in cell lysates of fibroblasts (HFL-1), melanocytes (B16F10) and peripheral blood mononuclear cells (PBMCs) using fluorogenic peptide substrates in a mid-throughput 96-well plate format. Optimization involves the composition of cell lysis and assay buffers, and the determination of the concentrations of specific fluorogenic substrates and protein content in the reaction to attain appropriate linear catalytic response during measurement. Additional parameters assessed include the concentration of the cell lysate and of ATP in the cell lysis and assay buffers. Our methodological analysis provides useful guidelines for the accurate and rapid determination of proteasome activity in various cell types.


Endogenous beta-amyloid peptide synthesis modulates cAMP response element-regulated gene expression in PC12 cells.
Extracellular-regulated kinases play a fundamental role in several neuroplasticity processes. In order to test whether endogenous beta-amyloid peptides play a role in the activation of extracellular-regulated kinase, we investigated the Rap1-extracellular-regulated kinase pathway in PC12 cells expressing human beta-amyloid precursor protein containing familial Alzheimer's disease mutations. In PC12 cells transfected with mutant human beta-amyloid precursor proteins that lead to higher levels of endogenous beta-amyloid, we observed an up-regulation of phospho-extracellular-regulated kinase and higher levels of activity-induced cAMP response element-directed gene expression. These results suggest that moderate levels of endogenous beta-amyloid peptides stimulate cAMP response element-directed gene expression. This stimulation was via a Rap1/MEK/extracellular-regulated kinase signaling pathway, as it was blocked by inhibition of Rap1 and MEK activities, and it requires beta-amyloid precursor protein cleavage at the gamma-site as it was abolished by a gamma-secretase inhibitor. Interestingly, in agreement with the previous observations, micromolar levels of extracellular fibrillar beta-amyloid blocked the cAMP response element-regulated gene expression stimulated by potassium and forskolin. This indicates that beta-amyloid can provoke different responses on cAMP response element-directed gene expression, such that low beta-amyloid levels may play a physiological role favoring synaptic plasticity under normal conditions while it would inhibit this mechanism under pathological conditions.


A tradeoff between musical tension perception and declarative memory.
Successful formation of long-term declarative memory is influenced, among other things, by attention, emotion, and deviation from expectations. A unique form of expectation can be elicited through musical tension, evoked by the prolongation of certain musical progressions. We examined the effect that musical tension exerts on the formation of declarative memory, by composing three original music pieces that contained tension segments, achieved by delays in release from dominant to tonic harmonies. Music-evoked tension was validated using music information retrieval (MIR) analysis, as well as skin conductance response (SCR) measures. Indeed, tension-evoking musical excerpts were associated with heightened SCR, corroborated by increased subjective ratings of tension, as compared to neutral excerpts. In the main experiment, 50 participants listened to the three musical pieces while they were presented with unique images that were randomly assigned to four conditions: tension, tension-release, neutral music, and silence. One day later, their memory for the images was examined using a recognition test. We found that memory performance was enhanced for images presented during both neutral and tense music compared to silence. Moreover, we observed a tradeoff effect between post-experiment tension perception and memory, such that individuals who perceived musical tension as such displayed reduced memory performance for images encoded during musical tension, whereas tense music benefited memory for those with lower musical tension perception. Understanding the interrelations between musical components, which exert powerful and fundamental responses in humans, and cognitive faculties, may provide insights as to the basic features of memory formation.


Determination of the absolute stereostructure of seco-macrosphelide E produced by a fungal strain from a sea hare.
seco-Macrosphelide E has been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai. Its absolute stereostructure, with the same configuration as that of macrosphelide E, have been elucidated on the basis of spectroscopic analyses and unambiguous synthesis.


[Progressive nuclear ophthalmoplegic myopathy with retinitis pigmentosa, scrotal tongue and intellectual deterioration--a nosologically independent syndrome?].
This is the second reported description in the available literature of a family with nuclear ophthalmoplegic myopathy, pigment retinitis, scrotal tongue and intellectual deterioration. Nosological independence of the syndrome is discussed.


Ectopic thymus as a cause of Horner's syndrome.
Ectopy of the thymus is a rare anomaly arising during fetal development, where the thymus does not make a complete decent into the thoracic cavity where it should involute in adolescence. The most common complications of an ectopic thymus include tracheal or esophageal compression presenting in childhood. This is a report of a single case of ectopic cervical thymus identified in a 2-month-old infant presenting with Horner's syndrome. Thymic ectopy should be on the differential when performing a radiologic evaluation of a neck mass when imaging characteristics are similar to thymic tissue.


jSquid: a Java applet for graphical on-line network exploration.
jSquid is a graph visualization tool for exploring graphs from protein-protein interaction or functional coupling networks. The tool was designed for the FunCoup web site, but can be used for any similar network exploring purpose. The program offers various visualization and graph manipulation techniques to increase the utility for the user. jSquid is available for direct usage and download at http://jSquid.sbc.su.se including source code under the GPLv3 license, and input examples. It requires Java version 5 or higher to run properly. firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Timing of specimen collection is crucial in urine screening of drug dependent mothers and newborns.
We compared results of urine drug analysis with clinical data and history to test the usefulness of peripartum drug screening and to establish guidelines for optimal testing. Urine from 28 mothers and 52 babies was analysed. Drugs not suspected by history were found in 10 mothers and six babies. Results assisted in the management of neonatal withdrawal in three babies. Drugs suspected by history were not found in 11/22 mothers and 23/35 babies. About half of these results were associated with delayed urine collection. In 12/28 mothers, drugs administered in hospital could have confused interpretation of screen results. We conclude that urine drug screening without strict protocols for specimen collection is of limited usefulness for management of drug abuse in pregnancy and neonatal drug withdrawal. We favour testing of maternal urine obtained before drugs are administered in hospital. Neonatal urine, if used, should be collected in the first day of life.


Superoxide and hydrogen peroxide suppression by metal ions and their EDTA complexes.
Redox-active metal ions such as Fe(II)\(III) and Cu(I)\(II) have been proposed to activate reactive oxygen and nitrogen species (RONS) and thus, perpetuate oxidative damage. Here, we show that concentrations of metal ions and EDTA complexes with superoxide-destroying activities equivalent to 1 U SOD are Fe(III) 5.1 microM, Mn(II) 0.77 microM, Cu(II)-EDTA 3.55 microM, Fe(III)-EDTA 2.34 microM, and Mn(II)-EDTA 1.38 microM. The most active being the aquated Cu(II) species which exhibited superoxide-destroying activity equivalent to 2U of SOD at 0.29 microM. Hydrogen peroxide-destroying activities were as follows Fe(III)-EDTA ca. 70 U/mg and aquated Fe(III) 141 U/mg. In contrast, DTPA prevented superoxide-destroying activity and significantly depleted hydrogen peroxide-destroying activity. In conclusion, non-protein bound transition metal ions may have significant anti-oxidant effects in biological systems. Caution should be employed in bioassays when chelating metal ions. Our results demonstrate that DTPA is preferential to EDTA for inactivating redox-active metal ions in bioassays.


Influence of urinary tract instrumentation and inflammation on the performance of urine markers for the detection of bladder cancer.
To evaluate the impact of inflammation and sampling on cytology, immunocytology, and fluorescence in situ hybridization (FISH) in comparison with NMP22 in hematuria patients. The specificity of urine markers for urothelial cancer is subject to exogenous factors. There is evidence that nuclear matrix protein 22 (NMP22) is influenced by urinary tract infection and instrumented urinary sampling (IUS). Samples from 1386 patients with histologic work-up were included. Cytology, immunocytology, FISH, and NMP22-enzyme-linked immunosorbent assay were performed. The presence of inflammation was evaluated by microscopy. The method of urine sampling was recorded in all cases. Any type of urinary tract manipulation was considered as IUS. False-positive results were compared with regard to the presence or absence of inflammation and mechanical manipulation. In all, 1050 (75.7%) patients had no evidence of urothelial cancer. NMP22 results were false positive in 74.3% and 38.4% of patients with and without IUS (P < .0001). False-positive test rates of cytology, immunocytology, and FISH were not increased after manipulation. Inflammation led to a rise in false-positive NMP22 test results (85.3% vs 61.4%, P < .0001). The presence of inflammation did not change the rate of false-positive cytology, immunocytology, and FISH results. This is the first study to investigate the impact of inflammation and IUS on cell-based urine markers. In contrast to the protein test NMP22, these factors did not impair the performance of cell-based tests. Hence, patients with positive cytology, immunocytology, and FISH results should undergo diagnostic work-up, even in the case of concomitant inflammation or IUS.


Latissimus dorsi transfer for irreparable subscapularis tear.
There is a paucity of information on latissimus dorsi transfer (LDT) for subscapularis insufficiency. The purpose of this study is to report the outcome of LDT to reconstruct an irreparable subscapularis tear. Excluding patients with prior failed Latarjet procedures, we examined 56 consecutive patients who underwent open (n = 14) or arthroscopic (n = 42) LDT. The average age was 53 years (range, 23-79), and 46 patients had a prior surgery. Outcome measures included visual analog scale score for pain, range of motion (ROM), subjective shoulder value (SSV), and Constant shoulder score (CSS). At a mean 13-month follow-up (7-51 months), patients had significant improvements in their pain, ROM, SSV, and CSS when compared to preoperatively. At final follow-up, 26% of patients continued to have proximal migration, and 11% of patients had anterior subluxation. The patients with frank anterior escape had a higher likelihood of having proximal migration and anterior subluxation, but this was not statistically significant. Stages of arthritis did not progress. Revision surgeries included 2 patients who revised to a reverse shoulder arthroplasty for rupture of the tendon transfer. Furthermore, 3 patients had LDT ruptures but did not elect to undergo further surgery. LDT for irreparable subscapularis tears has the potential to lead to significant clinical improvements. Most patients improve in many of the signs of subscapularis insufficiency, including anterior and/or proximal subluxation, clinical examination maneuvers, and shoulder function. Overall, this transfer represents a reasonable option for this difficult pathology.


Disabling pansclerotic morphea of childhood and hypogammaglobulinemia: a curious association.
This communication describes a 1.5-year-old girl who presented with multiple episodes of infection since early infancy and stiffening of limbs for 2 months. Biopsy of the involved areas showed features consistent with pansclerotic morphea. Immunoglobulin estimation revealed hypogammaglobulinemia. This unique combination of pansclerotic morphea with hypogammaglobulinemia has not been reported before.


Referral and Management Considerations for a Biopsy: Why Choose the Oral and Maxillofacial Surgeon.
Traditional oral and maxillofacial surgeon office practice spans the full scope of patient management. Most surgeons practicing in the United States dedicate their primary focus to the needs of patients referred by our dental colleagues. Dentoalveolar surgical practice remains the mainstay of office-based care. Oral cavity disease typically occurs from chronic bacterial infections of carious teeth, chronic periodontitis, fractured teeth. Recognition of oral disease patterns occurs by medical and dental clinicians. Oral and maxillofacial surgeon practice is uniquely designed to provide choice for the diagnosis and management of oral cavity disease, including neoplastic oral cavity and maxillofacial mucocutaneous disease.


[Epigenetic regulation of gene expression in malignant melanoma].
Malignant melanoma is a highly aggressive cancer with a propensity for early metastasis. Melanocyte transformation results predominantly from oncogenic mutations in BRAF, NRAS or NF1 leading to constitutive activation of the MAP kinase pathway driving cell proliferation and second site mutations such as loss of CDKN1A, or PTEN or activating mutations in the beta-catenin pathway that allow escape from oncogene induced senescence. Nevertheless, irrespective of the nature of the driver mutations, melanoma cell physiology is strongly regulated by transcription factors and epigenetic mechanisms. MITF (Microphthalmia-associated Transcription Factor) and SOX10 are two major transcription factors that regulate both normal melanocyte and melanoma cell physiology. Using a combination of mouse genetics, biochemistry and high throughput genomics we have identified cofactors for MITF and addressed the mechanisms by which MITF, SOX10 and their cofactors regulate gene expression in melanocytes and melanoma.


Can SARS-CoV-2 vaccine increase the risk of reactivation of Varicella zoster? A systematic review.
Although the COVID-19 vaccination is deemed safe, exact incidence and nature if adverse effects, particularly dermatological ones, are still unknown. To describe the demographic, clinical, morphological characteristics, outcomes, and timing of development of herpes zoster to the various COVID-19 vaccines. And to identify on whether COVID-19 vaccine has temporal relationship between development of herpes zoster (HZ). We have performed a systemic review of articles from PubMed and Embase using MeSH and keywords like "Shingles," "Herpes zoster," "Varicella zoster," "COVID-19," "Vaccine," "SARS-CoV-2." No filters including country of publication, language, type of articles were applied. Individual case report references were filtered for any pertinent cases. A total of 54 cases consisting of 27 male and 27 female patients have been reported. There were cases with known risk factors for herpes zoster, which included age more than 50 years (n = 36), immunological disorders (n = 10), chronic disease (n = 25), metabolic disorder (n = 13), malignancy (n = 4), and psychiatric disorder (n = 2). The mean (SD) period between development of herpes zoster and COVID-19 vaccination was 7.64 (6.92) days. Majority of the cases were from the high-income and/or middle-income countries. 86.27% of the cases of HZ were reported due to mRNA vaccine. Thirty-six patients 36/45 (80%) developed herpes zoster following the priming dose of COVID-19 vaccine among those who received mRNA vaccine. We could not establish definite link but there may be possible association between COVID-19 vaccine and shingles. Large-scale studies may help to understand the cause-effect relationship.