Skin Impedance Estimation System for Voltage-mode Electrical Stimulator with an AC Bridge Circuit.
Neuromuscular electrical stimulation is used to improve the motor function of paralyzed limbs and prevent muscle atrophy in stroke patients. The system for electrical stimulation is broadly classified into current-mode stimulators and voltage-mode stimulators. The current-mode stimulator adjusts the amplitude of the current, whereas the amplitude of the voltage is adjusted for voltage-mode stimulators. Voltagemode stimulators have the advantage that there is little risk of burns even if the electrode is partially detached. To perform arbitrary current-mode stimulation with voltage-mode stimulators, it is necessary to generate a stimulating voltage based on the skin impedance. As a primary experiment, the frequency characteristics of the electrode-skin impedance were measured using an impedance analyzer on 6 subjects, and the frequency band in which the skin impedance is equivalent to a parallel connection between resistance and capacitance was determined. A prototype bridge circuit with a skin impedance equivalent circuit implemented was designed, assembled, and tested to estimate the skin impedances of 3 subjects. The residuals were computed from the estimated skin-impedance resistance and capacitance of the bridge circuit, and the impedance-analyzer-measured resistance and capacitance. The residuals between the estimated and measured were up to 4.4 % in the resistance component, and up to 8.2 % in the capacitance component of the skin impedance measurements by the impedance analyzer.


Relationship between General Health Behaviors and Oral Health Behaviors in 2015-2016 NHANES Adult Population.
The aim of this study was to examine the relationship between general health behaviors and oral health behaviors in adults who participated in the interview component of the National Health and Nutrition Examination Survey (NHANES) of 2015 to 2016. This was a cross-sectional study design of a national data set that included 5,992 adults who represented a sample of civilian, noninstitutionalized US population. Chi-squared test of independence was used to describe the relationship of demographic information with oral health behaviors of participants. Multivariate logistic regression was used to determine the association between general and oral health behaviors. More than half (53.6%) of the participants had seen a dentist in the past 12 months and the main reason for that visit was for a regular checkup, cleaning, or examination. More than one-quarter (28.7%) reported visiting a dentist because something was hurting or bothering them. Most respondents (63.4%) reported being hardly ever or never having been embarrassed by their mouth condition. Age at one's first sexual encounter, having a new sexual partner, mental health counseling, moderate- intensity sports, and computer use were significantly associated with positive oral health behaviors. For maximum effectiveness, health promotion efforts should target risk behaviors common to both oral and general health.


[Population analysis CTG trinucleotide repeats in the myotonin-protein kinase I gene].
CTG trinucleotide repeat length polymorphism within the 3' region of the myotonin protein kinase I (MP-I) gene was examined with the use of the polymerase chain reaction (PCR) technique. A total of 159 DNA samples from healthy donors from five ethnic groups including Russians (n = 33), Azerbaijanians (n = 29), Uzbeks (n = 31), Moldavians (n = 31), and Georgians (n = 35) were analyzed. The number of CTG repeats varied from 5 to 24, and allele distribution was bimodal in all populations; alleles with 6, 7 and 9 repeats were not found. Statistical treatment of the data was performed by the contingency table collapsing procedure. Allele distribution in the populations of Russians, Azerbaijanians, Uzbeks and Georgians appeared to be statistically homogenous and significantly (P < 0.001) different from that in Moldavians as well as in Japanese, African, and Western European populations. High heterozygosity levels of all populations, studied (72-86%) indicate the usefulness of this polymorphism in population and genome fingerprinting studies.


Self-Catalyzed Growth and Characterization of In(As)P Nanowires on InP(111)B Using Metal-Organic Chemical Vapor Deposition.
We report the growth of vertical <111>-oriented InAs x P1-x (0.11 ≤ x ≤ 0.27) nanowires via metal-organic chemical vapor deposition in the presence of indium droplets as catalysts on InP(111)B substrates at 375 °C. Trimethylindium, tertiarybutylphosphine, and tertiarybutylarsine are used as the precursors, corresponding to P/In and As/In molar ratios of 29 and 0.01, respectively. The as-grown nanowire growth morphologies, crystallinity, composition, and optical characteristics are determined using a combination of scanning and transmission electron microscopies, electron diffraction, and X-ray photoelectron, energy dispersive X-ray, and Raman spectroscopies. We find that the InAs x P1-x nanowires are tapered with narrow tops, wider bases, and In-rich In-As alloy tips, characteristic of vapor-liquid-solid process. The wires exhibit a mixture of zinc blende and wurtzite crystal structures and a high density of structural defects such as stacking faults and twins. Our results suggest that the incorporation of As into InP wires decreases with increasing substrate temperature. The Raman spectra obtained from the In(As)P nanowires reveal a red-shift and lower intensity of longitudinal optical mode relative to both InP nanowires and InP(111)B bulk, due to the incorporation of As into the InP matrix.


Following the Chemical Immobilization of Membrane Proteins on Plasmonic Nanoantennas Using Infrared Spectroscopy.
Plasmonic nanoantennas are promising sensing platforms for detecting chemical and biological molecules in the infrared region. However, integrating fragile biological molecules such as proteins on plasmonic nanoantennas is an essential requirement in the detection procedure. It is crucial to preserve the structural integrity and functionality of proteins while attaching them. In this study, we attached lactose permease, a large membrane protein, onto plasmonic nanoantennas by means of the nickel-nitrile triacetic acid immobilization technique. We followed the individual steps of the immobilization procedure for different lengths of the nanoantennas. The impact of varying the length of the nanoantennas on the shape of the vibrational signal of the chemical layers and on the protein spectrum was studied. We showed that these large proteins are successfully attached onto the nanoantennas, while the chemical spectra of the immobilization monolayers show a shape deformation which is an effect of the coupling between the vibrational mode and the plasmonic resonance.


Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis.
Miltefosine is an alkylphosphocholine drug with demonstrated activity against various parasite species and cancer cells as well as some pathogenic bacteria and fungi. For 10 years it has been licensed in India for the treatment of visceral leishmaniasis (VL), a fatal neglected parasitic disease. It is the first and still the only oral drug that can be used to treat VL and cutaneous leishmaniasis (CL). The standard 28 day miltefosine monotherapy regimen is well tolerated, except for mild gastrointestinal side effects, although its teratogenic potential severely hampers its general use in the clinic and roll-out in national elimination programmes. The pharmacokinetics of miltefosine are mainly characterized by its long residence time in the body, resulting in extensive drug accumulation during treatment and long elimination half-lives. At the moment, different combination therapy strategies encompassing miltefosine are being tested in multiple controlled clinical trials in various geographical areas of endemicity, both in South Asia and East Africa. We here review the most salient pre-clinical and clinical pharmacological aspects of miltefosine, its mechanism of action against Leishmania parasites and other pathogens, and provide a systematic overview of the efficacy and safety data from all clinical trials of miltefosine, either alone or in combination, in the treatment of VL and CL.


Endocytosis of Multiwalled Carbon Nanotubes in Bronchial Epithelial and Mesothelial Cells.
Bronchial epithelial cells and mesothelial cells are crucial targets for the safety assessment of inhalation of carbon nanotubes (CNTs), which resemble asbestos particles in shape. Intrinsic properties of multiwalled CNTs (MWCNTs) are known to cause potentially hazardous effects on intracellular and extracellular pathways. These interactions alter cellular signaling and affect major cell functions, resulting in cell death, lysosome injury, reactive oxygen species production, apoptosis, and cytokine release. Furthermore, CNTs are emerging as a novel class of autophagy inducers. Thus, in this study, we focused on the mechanisms of MWCNT uptake into the human bronchial epithelial cells (HBECs) and human mesothelial cells (HMCs). We verified that MWCNTs are actively internalized into HBECs and HMCs and were accumulated in the lysosomes of the cells after 24-hour treatment. Next, we determined which endocytosis pathways (clathrin-mediated, caveolae-mediated, and macropinocytosis) were associated with MWCNT internalization by using corresponding endocytosis inhibitors, in two nonphagocytic cell lines derived from bronchial epithelial cells and mesothelioma cells. Clathrin-mediated endocytosis inhibitors significantly suppressed MWCNT uptake, whereas caveolae-mediated endocytosis and macropinocytosis were also found to be involved in MWCNT uptake. Thus, MWCNTs were positively taken up by nonphagocytic cells, and their cytotoxicity was closely related to these three endocytosis pathways.


Impact of Preprocedural Left Ventricular Ejection Fraction on 1-Year Outcomes After MitraClip Implantation (from the ACCESS-EU Phase I, a Prospective, Multicenter, Nonrandomized Postapproval Study of the MitraClip Therapy in Europe).
This report describes the 12-month outcomes of the a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe (ACCESS-EU postapproval study of MitraClip therapy) with respect to preprocedural left ventricular ejection fraction (LVEF). Transcatheter deployment of the MitraClip device may be considered for patients who are not suitable for conventional surgery. A total of 567 patients with significant mitral regurgitation (MR) underwent MitraClip therapy. Of those, 393 had functional MR (FMR) and were subdivided by preprocedural LVEF (A: 10% to 20%, B: >20% to 30%, C: >30% to 40%, D: >40%). Procedural safety and efficacy and treatment outcomes including MR grade, New York Heart Association (NYHA) functional class, 6-minute walk test, and the Minnesota Living with Heart Failure Questionnaire were analyzed at baseline, 30 days, and 12 months. Baseline mean logistic EuroSCORE was 25 ± 19; 87% of patients were in NYHA classes III or IV (A: 96%, B: 83%, C: 90%, D: 86%). There was no incidence of death or stroke intraprocedurally. Eleven patients died within 30 days with no differences among subgroups. Kaplan-Meier survival at 12 months was 81.8% (A: 71%, B: 79%, C: 87%, D: 86%). There was a significant improvement in MR severity at 30 days and 12 months (p <0.0001). At 12 months, all subgroups experienced similar improvements in NYHA class, 6-minute walk test, and Minnesota Living with Heart Failure Questionnaire. This real-world registry reports promising results of MitraClip therapy in patients with FMR. In conclusion, the low rates of hospital mortality and adverse events in patients with FMR-even in patients with severely reduced LVEF-provide additional evidence of substantial benefits after MitraClip implantation.


Home-based drainage of refractory ascites by a permanent-tunneled peritoneal catheter can safely replace large-volume paracentesis.
Refractory ascites has a poor prognosis. Recurrent large-volume paracentesis is the current standard of care; however, it results in circulatory dysfunction and renal dysfunction, and hospitalization is commonly required. Transjugular intrahepatic portosystemic shunt placement is not an option in a substantial number of patients because of contraindications. The placement of a tunneled peritoneal drainage catheter has been shown to be effective in patients with malignant ascites. However, data in patients with nonmalignant refractory ascites are rare. We followed 24 consecutive patients in whom tunneled peritoneal drainage catheters were placed in the Endoscopy Unit at Hannover Medical School between June 2013 and December 2014. Catheters were placed in 24 patients with refractory ascites in end-stage liver disease and with a contraindication to transjugular intrahepatic portosystemic shunt placement. Placement was technically successful in all patients. The dosage of diuretics could be reduced significantly. The number of paracentesis decreased from 2.2±1 to 0 per week, although the volume of daily ascites removal remained stable (2 l). Despite frequent drainage of ascites, kidney function, serum sodium, and serum albumin remained stable. Seven adverse events occurred in six (25%) patients. Five patients listed for liver transplantation underwent successful transplantation without a negative impact. The tunneled peritoneal drainage catheter placement is a viable and effective treatment alternative in patients with refractory ascites because of end-stage liver disease, reducing diuretic intake and the need for paracentesis. The procedure avoids hyponatremia, worsening kidney function, and albumin infusions without an increased risk of spontaneous bacterial peritonitis.


Barcoding Atlantic Canada's mesopelagic and upper bathypelagic marine fishes.
DNA barcode sequences were developed from 557 mesopelagic and upper bathypelagic teleost specimens collected in waters off Atlantic Canada. Confident morphological identifications were available for 366 specimens, of 118 species and 93 genera, which yielded 328 haplotypes. Five of the species were novel to the Barcode of Life Database (BOLD). Most of the 118 species conformed to expectations of monophyly and the presence of a "barcode gap", though some known weaknesses in existing taxonomy were confirmed and a deficiency in published keys was revealed. Of the specimens for which no firm morphological identification was available, 156 were successfully identified to species, and a further 11 to genus, using their barcode sequences and a combination of distance- and character-based methods. The remaining 24 specimens were from species for which no reference barcode is yet available or else ones confused by apparent misidentification of publicly available sequences in BOLD. Addition of the new sequences to those previously in BOLD contributed support to recent taxonomic revisions of Chiasmodon and Poromitra, while it also revealed 18 cases of potential cryptic speciation. Most of the latter appear to result from genetic divergence among populations in different ocean basins, while the general lack of strong horizontal environmental gradients within the deep sea has allowed morphology to be conserved. Other examples of divergence appear to distinguish individuals living under the sub-tropical gyre of the North Atlantic from those under that ocean's sub-polar gyre. In contrast, the available sequences for two myctophid species, Benthosema glaciale and Notoscopelus elongatus, showed genetic structuring on finer geographic scales. The observed structure was not consistent with recent suggestions that "resident" populations of myctophids can maintain allopatry despite the mixing of ocean waters. Rather, it indicates that the very rapid speciation characteristic of the Myctophidae is both on-going and detectable using barcodes.


Interobserver agreement between on-call radiology residents and radiology specialists in the diagnosis of pulmonary embolism using computed tomography pulmonary angiography.
The objective of this study was to assess the interobserver agreement between on-call radiology residents and radiology specialists in the evaluation of pulmonary embolism (PE) using computed tomographic pulmonary angiography (CTPA). Single center, prospective cohort study of 119 consecutive inpatients and outpatients with clinically suspected PE in whom CTPA was performed during out-of-office hours and weekends. The on-call radiology resident interpreted the CTPA for the presence of PE. An experienced radiology specialist, without knowledge of earlier reading, reviewed the CTPA the following morning. In discordant cases, a consensus reading was conducted. The radiology specialists' assessment and the consensus reading in case of discordance were considered as the gold standard. Five CTPA studies were excluded from the analysis. In the remaining cases, radiology residents and radiology specialists agreed on the interpretations of CTPAs (no PE vs PE present) in 106 (93%) of the 114 cases, with a kappa value of 0.84 (95% confidence interval, 0.74-0.95). The consensus reading equally disagreed with both radiology resident and radiology specialist in 8 (7%) of the 114 discordant cases. Seven out of 8 discordant cases had suboptimal scan quality. The assessment of CTPA in patients with suspected PE by radiology residents seems reliable during out-of-office hours.


Transitory macrophage activation in the granulomatous lesions of Mycobacterium lepraemurium-induced lepromatoid leprosy in the mouse.
A kinetic study on the evolution of granulomas that appear in the liver of NIH mice inoculated with 10(8) Mycobacterium lepraemurium by the intraperitoneal route has been performed. The liver was chosen because of its nonlymphoid histology which allowed us to visualize the appearance and maturation of the cell infiltrates generated as a consequence of the mycobacterial infection. The study analyzed both the macrophage activation within the granulomas and the fate of bacilli within the macrophage. The results showed that this mycobacteriosis induces a relatively early macrophage activation (a very likely result of a cell-mediated immune response triggered by the bacilli) that peaks between 45 and 60 days postinoculation, fades thereafter, and practically disappears several days later. Bacilli are susceptible to the microbicidal effects of activated macrophages, but when the macrophages are turned off (probably due to active suppressive mechanisms), the surviving bacilli reinitiate the infection with no further macrophage opposition. As a result, more phagocytes are attracted to the infection sites and the cell infiltrates grow steadily to become confluent, increasing the granuloma fraction and eventually replacing the liver parenchyma. The findings suggest that in murine "leprosy" infection, early immunological changes occur that enable the macrophages present in the granulomas to kill the infecting M. lepraemurium regardless of the eventual lepromatoid evolution of the granulomas. Lepromatoid granulomas in the mouse and lepromatous granulomas in man are equivalent structures in regard to their histology and bacteriology.


Validation of remote assessment of preschool children's anthropometrics and motor skills.
Remotely delivered treatment and research procedures were rapidly adopted in response to the COVID-19 pandemic. However, it is unclear if these measures are valid. The purpose of this study was to compare the validity of anthropometry and motor skill proficiency measurements collected in a remote-setting to in-person setting among a sample of children ages 3-4 years. Child anthropometry and motor skill performance were measured in-person by trained assessors and by parents at home with remote supervision via videoconference by trained assessors. The following measures from the National Institutes of Health Toolbox were collected: anthropometry (height and weight), manual dexterity/manipulation (9-hole pegboard), motor coordination and agility (supine timed up and go), lower body strength (standing long jump), and postural stability (one-leg standing balance). Differences in expert and parent-based measurements were assessed using Bland-Altman plots, paired samples t-tests, and Pearson correlations. A total of n = 14 children completed the assessments. No significant differences were observed between measurement locations for weight and motor skills (p > .05). Remote measurement of height (M = 101.1 cm, SD = 5.40) was significantly greater than in-person measurements (M = 98.2 cm, SD = 5.16); p < .0001. Remote measurements of motor skills and weight are valid assessments for researchers and clinicians to utilize in young children. Remote assessment with guidance offers comparable and valid estimates as in-person assessment, potentially offering a solution to resource-constricted barriers in research and access to care. There is an opportunity for researchers to fine-tune remote height and individual-level assessment strategies.


Prognostic relevance of uncommon ovarian histology in women with stage III/IV epithelial ovarian cancer.
The prognostic relevance of uncommon epithelial ovarian cancer (EOC) histological subtypes remains controversial. The Gynecologic Cancer InterGroup (GCIG) initiated this meta-analysis to assess the relative prognosis of women with a diagnosis of rare EOC histologies from completed, prospectively randomized studies performed by cooperative GCIG study groups. Studies eligible for analysis included first-line treatment of at least 150 patients with stage III/IV EOC treated with a platinum/taxane-based regimen. Collaborating groups were to provide patient-level data. Serous acted as the reference histology, and a proportional hazards model was used to estimate the relative rate of progression or death. Data on 8704 women with stage III/IV EOC from 7 randomized trials were included in these analyses. Two hundred twenty-one patients (2.5%) had clear cell carcinoma; 264 (3.0%), mucinous; and 36 (0.4%), transitional cell. The mean age of patients with serous histology was greater than those with mucinous (4.1 years) and clear cell (2.6 years, P < 0.001). Mucinous, clear cell, and transitional cell tumors were more likely to be completely resected than serous (P < 0.05). When controlling for age and residual disease, mucinous and clear cell tumors had shorter times to progression (hazards ratio [HR], 2.1; 95% confidence interval [CI], 1.8-2.4 and HR, 1.6; 95% CI, 1.4-1.9, respectively) and death (HR, 2.7; 95% CI, 2.3-3.1 and HR, 2.2; 95% CI, 1.8-2.6, respectively) compared with serous. The median overall survival for serous, clear cell, mucinous, and endometrioid histologies were 40.8, 21.3, 14.6, and 50.9 months. Mucinous and clear cell carcinomas are independent predictors of poor prognosis in stage III/IV EOC. Studies targeting these rare histological subtypes are warranted and will require significant intergroup collaboration.


Long-lasting effects of family-related factors on adults' ability to recognise brief facial expressions of emotion.
This study investigated whether adults' ability to attribute emotions to brief facial expressions (microexpressions) is associated with family-related environmental factors (FrFs) such as one's number of siblings (Experiment 1), attachment style (Experiment 2), or perceived parental authority style (Experiment 3). Participants' accuracy and reaction time (RT) to the recognition of anger, contempt, disgust, fear, happiness, and sadness to facial microexpressions (exposure: 100 ms) were measured with a six-alternative forced choice computerised method (6AFC). The attachment style and the authority style of the participants' parents were accessed using questionnaires. The findings revealed that up to 13% of the variance in participants' responses could be explained by FrFs, with modest to moderate effect sizes. Microexpressions linked to signs of hostility or threat (i.e., contempt and fear) were decoded faster and/or more accurately by adults with few or no siblings or with a fearful attachment. Conversely, participants who recalled their fathers as authoritarian were worse at recognising contempt and fear than participants who perceived them as permissive or authoritative. The findings suggest that early FrFs may still be involved in the fine-tuning of responses to signs of contextual danger when the time for cognitive processing of facial expressions is severely restricted.


Clinical significance of serum and urinary neopterins in patients with chronic renal disease.
To determine the clinical significance of serum and urinary neopterins in patients with chronic renal disease, we measured these values using IMMUtest Neopterin RIA kits. Serum neopterin levels in patients with chronic glomerulonephritis (CGN) (10.2 +/- 8.1 nmol/l) and in those with chronic renal failure (CRF) (109 +/- 90) were significantly increased compared with the control subjects (C) (4.2 +/- 2.4) (p less than 0.001). The levels of serum neopterins in patients on chronic hemodialysis (HD) (212 +/- 106) were increased almost twofold compared with CRF (p less than 0.001). In CGN and CRF, a strong positive correlation was demonstrated between serum neopterin levels and serum creatinine concentrations (r = 0.95, p less than 0.001). In HD patients, neopterin levels and serum were not correlated with the length of time on dialysis. The urinary neopterin excretion ratios (urinary neopterin/urinary creatinine level) in CRF (227 +/- 114 mumols/molCr) were significantly increased compared with C (116 +/- 43) (p less than 0.01). A significantly negative correlation was observed between the urinary neopterin levels and the creatinine clearance in CGN and CRF (p less than 0.01). These data suggest that, in patients with chronic renal disease, the neopterin levels in serum are closely linked with glomerular filtration rate and yet the urinary neopterin/creatinine ratios may reflect the predominance of increased tubular secretion of neopterin over the renal injury per se.


Bovine milk-derived extracellular vesicles enhance inflammation and promote M1 polarization following agricultural dust exposure in mice.
Occupational agricultural dust exposure can cause severe lung injury, including COPD and asthma exacerbations. Cell-derived extracellular vesicles can mediate inflammatory responses and immune activation, but the contribution of diet-derived extracellular vesicles to these processes is poorly understood. We investigated whether bovine milk-derived extracellular vesicles modulate inflammatory responses to agricultural dust exposures in a murine model. C57BL/6 mice were fed either an extracellular vesicle-enriched modification of the AIN-93G diet with lyophilized bovine milk (EV) or a control diet wherein the milk was presonicated, disrupting the milk extracellular vesicles and thereby leading to RNA degradation (DEV). Mice were maintained on the diets for 5-7 weeks and challenged with a single (acute) intranasal instillation of a 12.5% organic dust extract (DE) or with 15 instillations over 3 weeks (repetitive exposure model). Through these investigations, we identified significant interactions between diet and DE when considering numerous inflammatory outcomes, including lavage inflammatory cytokine levels and cellular infiltration into the lung airways. DE-treated peritoneal macrophages also demonstrated altered polarization, with EV-fed mouse macrophages exhibiting an M1 shift compared to an M2 phenotype in DEV-fed mice (IL-6, TNF, IL-12/23 all significantly elevated, and IL-10 and arginase decreased in EV macrophages, ex vivo). In complementary in vitro studies, mouse macrophages treated with purified milk-derived EV were found to express similar polarization phenotypes upon DE stimulation. These results suggest a role for dietary extracellular vesicles in the modulation of lung inflammation in response to organic dust which may involve macrophage phenotype polarization.


Uniqueness of the gaussian kernel for scale-space filtering.
Scale-space filtering constructs hierarchic symbolic signal descriptions by transforming the signal into a continuum of versions of the original signal convolved with a kernal containing a scale or bandwidth parameter. It is shown that the Gaussian probability density function is the only kernel in a broad class for which first-order maxima and minima, respectively, increase and decrease when the bandwidth of the filter is increased. The consequences of this result are explored when the signal¿or its image by a linear differential operator¿is analyzed in terms of zero-crossing contours of the transform in scale-space.


Optimal efficiency of quantum transport in a disordered trimer.
Disordered quantum networks, such as those describing light-harvesting complexes, are often characterized by the presence of peripheral ringlike structures, where the excitation is initialized, and inner structures and reaction centers (RCs), where the excitation is trapped and transferred. The peripheral rings often display distinguished coherent features: Their eigenstates can be separated, with respect to the transfer of excitation, into two classes of superradiant and subradiant states. Both are important to optimize transfer efficiency. In the absence of disorder, superradiant states have an enhanced coupling strength to the RC, while the subradiant ones are basically decoupled from it. Static on-site disorder induces a coupling between subradiant and superradiant states, thus creating an indirect coupling to the RC. The problem of finding the optimal transfer conditions, as a function of both the RC energy and the disorder strength, is very complex even in the simplest network, namely, a three-level system. In this paper we analyze such trimeric structure, choosing as the initial condition an excitation on a subradiant state, rather than the more common choice of an excitation localized on a single site. We show that, while the optimal disorder is of the order of the superradiant coupling, the optimal detuning between the initial state and the RC energy strongly depends on system parameters: When the superradiant coupling is much larger than the energy gap between the superradiant and the subradiant levels, optimal transfer occurs if the RC energy is at resonance with the subradiant initial state, whereas we find an optimal RC energy at resonance with a virtual dressed state when the superradiant coupling is smaller than or comparable to the gap. The presence of dynamical noise, which induces dephasing and decoherence, affects the resonance structure of energy transfer producing an additional incoherent resonance peak, which corresponds to the RC energy being equal to the energy of the superradiant state.


Bone formation following intrarenal transplantation of isolated murine chondrocytes: chondrocyte-bone cell transdifferentiation?
Isolated syngeneic epiphyseal chondrocytes transplanted into a muscle formed cartilage in which matrix resorption and endochondral ossification began at the end of the second week after transplantation. After 56 days cartilage was converted into an ossicle. In 7-day-old intrarenal transplants, epiphyseal chondrocytes formed nodules of cartilage. In 10-day-old transplants, islands of bone appeared. Slight resorption of cartilage was first noted in 14-day-old transplants of chondrocytes. After eight weeks, transplants contained mainly bone. Intramuscularly transplanted rib chondrocytes formed cartilage which did not ossify. Nevertheless, bone islands appeared in intrarenal transplants of rib chondrocytes. Bone was not formed in allogeneic intrarenal transplants of epiphyseal or rib chondrocytes, but appeared in such transplants in animals immunosuppressed by anti-thymocyte serum and procarbazine. When spleen cells from animals immunized with allogeneic chondrocytes were transferred to immunosuppressed chondrocyte recipients two weeks after intrarenal chondrocyte transplantation, the majority of osteocytes in bone islands was dead. On the other hand, endochondral bone formed in intramuscular transplants of allogenic epiphyseal chondrocytes in immunosuppressed recipients was not damaged by sensitized spleen cells. This suggested that bone in 10- to 14-day-old intrarenal transplants of chondrocytes arose from injected cells and not by induction. To see whether bone was formed by chondrocytes or by some cells contaminating the chondrocyte suspension, the superficial layer of rib cartilage was removed by collagenase digestion and only more central chondrocytes were used for transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)


Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials.
Immune responses to gene-modified cells are a concern in the field of human gene therapy, as they may impede effective treatment. We conducted 2 clinical trials in which cancer patients were treated with lymphocytes genetically engineered to express murine T-cell receptors (mTCR) specific for tumor-associated antigens p53 and gp100. Twenty-six patients treated with autologous lymphocytes expressing mTCR had blood and serum samples available for analysis. Patient sera were assayed for the development of a humoral immune response. Adoptive cell transfer characteristics were analyzed to identify correlates to immune response. Six of 26 (23%) patients' posttreatment sera exhibited specific binding of human anti-mTCR antibodies to lymphocytes transduced with the mTCR. Antibody development was found in both responding and nonresponding patients. The posttreatment sera of 3 of these 6 patients mediated a 60% to 99% inhibition of mTCR activity as measured by a reduction in antigen-specific interferon-γ release. Detailed analysis of posttreatment serum revealed that antibody binding was β-chain specific in 1 patient whereas it was α-chain specific in another. A subset of patients treated with mTCR-engineered T cells developed antibodies directed to the mTCR variable regions and not to the constant region domains common to all mTCR. Overall, the development of a host immune response was not associated with the level of transduced cell persistence or response to therapy. In summary, patients treated with mTCR can develop an immune response to gene-modified cells in a minority of cases, but this may not affect clinical outcome.


Neuropathy and Fabry disease: pathogenesis and enzyme replacement therapy.
The neurological manifestations of Fabry disease include both peripheral and central nervous system involvement caused by a deficiency of alpha-galactosidase A and accumulation of alpha-D-galactosyl moieties, particularly globotriosylceramide accumulation (Gb3). These are found in Schwann cells and dorsal root ganglia together with deposits in central nervous system neurons. Involvement of the peripheral nervous system affect mainly small Adelta and C fibers and are likely causally related to the altered autonomic function and neuropathic pain found in this disorder. Other related abnormalities to be discussed are hypohidrosis and other abnormalities attributed to autonomic nervous system dysfunction. The function of the peripheral nervous system is somewhat improved by ERT with reduction in neuropathic pain and an improvement of the detection threshold for cold and warm sensation in the hand and foot. Improvement in sweating and heat tolerance is also noted following ERT. Despite those positive results, ERT does not normalize the function of the peripheral nervous system.


The impact of prehospital resuscitation research on in-hospital care.
Since their introduction over 40 years ago, paramedics have been trained to deliver select advanced life support interventions in the community with the goal of reducing morbidity and mortality from cardiovascular disease and trauma. The ensuing decades witnessed a great deal of interest in paramedic care, with an exponential growth in prehospital resuscitation research. As part of the CJEM series on emergency medical services (EMS), we review recent prehospital research in out-of-hospital cardiac arrest and discuss how, in a novel departure from the origins of EMS, prehospital research is beginning to influence in-hospital care. We discuss emerging areas of study related to cardiopulmonary resuscitation (CPR) quality, therapeutic hypothermia, termination of resuscitation, and the use of end-tidal carbon dioxide measurement, as well as the subtle ripple effects that prehospital research is having on the broader understanding of the management of these critically ill patients.


Adherence to triage among women with HPV-positive self-collection: a study in a middle-low income population in Argentina.
Screening for cervical cancer (CC) prevention has substantially changed with the introduction of human papillomavirus (HPV) tests. This technology compared to cytology has increased the detection of pre-malignant and malignant cervical lesions in real-world programmes in different settings. Very importantly, through self-collection, HPV testing can reduce barriers to screening and increase coverage. However, when using HPV self-collection, triage tests are a key step in the CC prevention process, and high adherence to triage has been difficult to obtain in low-middle income settings. The aim of this study was to measure adherence to triage among women with HPV+ self-collection and analysed factors associated with this adherence in a middle-low resource setting in Argentina. We also evaluated key indicators related to the implementation of the HPV self-collection strategy. We analysed data on screening/triage/diagnosis/treatment from women aged 30+ who performed self-collection between 2015 and 2017 (n = 15,763), in the public health system in Tucuman, Argentina. We analysed secondary data from the national screening information system. The primary outcomes were: 1) adherence to cytology triage within the recommended timeframe (120 days) and 2) overall adherence to cytology triage including data at 18 months after screening. Multivariable regression was used to examine the association between age group, year of the screening test, record of the previous Pap-based screening and health insurance status with adherence to triage test as a primary outcome. We reported odds ratios, 95% confidence intervals and p-value of 0.05, which was considered the threshold for p-values). We analysed data of 2,389 HPV+ women. The overall adherence to triage at 18 months was 42.9%. The percentage of women completing cytology triage within the recommended timeframe of 120 days was lower (25.2%). Women with the record of a previous Pap-based screening had 1.86 times the odds of having a triage compared to women without a record of a previous Pap-based screening (95% CI: 1.64-2.64, p <0.001). Furthermore, the probability of having triage at the recommended timeframe was higher among women who were older and women with public health insurance. Our results showed that adherence to triage in the recommended timeframe was low. In addition, the probability of having triage at the recommended timeframe was higher among women with a record of a previous Pap-based screening, a proxy of the use of health services. Our results showed that adherence to triage in the context of the HPV-self-collection strategy is challenging. The implementation of alternative approaches that might facilitate adherence to triage should be further investigated.


Human interleukin-6 facilitates hepatitis B virus infection in vitro and in vivo.
Research on hepatitis B virus (HBV) infection in vivo has been limited due to the absence of a suitable animal model. We have developed a human-mouse radiation chimera in which normal mice, preconditioned by lethal total body irradiation and radioprotected with SCID mouse bone marrow cells, are permissive for engraftment of human hematopoietic cells and solid tissues. This resulting human-mouse model, which comprises three genetically disparate sources of tissue, is therefore termed Trimera. This study was aimed at assessing the effect of human IL-6 on HBV infection in vivo in Trimera mice. Trimera mice were transplanted with human liver tissue fragments or with HepG2-derived cell lines, which had been previously infected ex vivo with HBV in the presence or absence of human interleukin-6 (hIL-6) and in the presence of anti-IL-6-neutralizing antibodies. HBV sequences appeared in the sera of animals in which the liver tissue was incubated with both HBV and hIL-6 prior to transplantation. A similar result was obtained when a human hepatoblastoma cell line (HepG2), expressing the hIL-6 receptor, was infected ex vivo with HBV in the presence of hIL-6 prior to their injection into spleens of Trimera mice. However, when liver fragments were infected ex vivo and simultaneously treated with neutralizing antibodies against hIL-6 or were incubated with HBV prior to transplantation without hIL-6, the rate of mice positive for HBV DNA in their sera was lower. Human mononuclear cells are also permissive for HBV infection in vitro: in the presence of hIL-6 the infection of these cells is enhanced; and this infection is suppressed by the chimeric protein named Hyper-IL-6, generated by the fusion of hIL-6 to the soluble hIL-6 receptor (sIL-6Ralpha, gp80). hIL-6 facilitates HBV infection in vitro and in vivo.


Characterization of the permeability barrier of human skin in vivo.
Attenuated-total-reflectance Fourier-transform-infrared spectroscopy has been used to rapidly and noninvasively quantify in vivo the uptake of a chemical into the outermost, and least permeable, layer of human skin (the stratum corneum). The objective of the experiment was to develop a general model to predict the rate and extent of chemical absorption for diverse exposure scenarios from simple, and safe, short-duration studies. Measurement of the concentration profile of the chemical in the stratum corneum, and analysis of the data using the unsteady-state diffusion equation, enabled estimation of the permeability coefficient and calculation of the time required to achieve maximal transdermal flux. Validation of the spectroscopic technique employed was established, and quantitation of chemical uptake into the stratum corneum was confirmed independently using trace amounts of radiolabeled chemical in conjunction with liquid scintillation counting and accelerator mass spectrometry. The results presented have pharmacological and toxicological implications, as the technology lends itself both to the prediction of transdermal drug delivery, and the feasibility of this route of administration, and to the assessment of risk after dermal contact with toxic chemicals.


A perspective on gossypol ingestion in swine.
Cottonseed meal has been used for many years as a protein supplement in animal rations. Due to a polyphenol pigment, gossypol, present in cottonseed meal, its use for swine has been limited. The tolerance of gossypol for monogastric animals depends upon age and species with older animals being less sensitive than younger animals. Swine are highly susceptible to gossypol poisoning, and signs commonly develop after one or more months of consumption. The use of iron salts in the ration appears to be antidotal, and lysine supplementation of gossypol containing diets appears to improve gain. Reproductive performance can also be affected, including reduced conception and litter size. New extraction methodologies are being developed to reduce the amount of gossypol in cottonseed meal.


Prognostic Value of Natriuretic Peptide Levels for Adverse Renal Outcomes in Patients With Moderate to Severe Acute Kidney Injury With or Without Heart Failure.
Background Natriuretic peptides have been recommended as biomarkers for the diagnosis and prognosis of patients with heart failure and are often elevated in the setting of acute kidney injury. We sought to demonstrate the associations between increased baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) and adverse renal outcomes in patients with moderate-to-severe acute kidney injury. Methods and Results We reviewed electronic medical records of consecutive patients with acute kidney injury stage 2 and 3 admitted to the Cleveland Clinic between September 2011 and December 2021. Patients with NT-proBNP levels collected before renal consultation or dialysis initiation were included. Adverse renal outcomes included dialysis requirement and dialysis dependence defined as patients undergoing dialysis within 72 hours before hospital discharge or in-hospital mortality. In our study cohort (n=3811), 2521 (66%) patients underwent dialysis, 1619 (42%) patients became dialysis dependent, and 1325 (35%) patients had in-hospital mortality. After adjusting for cardiorenal risk factors, compared with the lowest quartile, the highest quartile of NT-proBNP (≥18 215 pg/mL) was associated with increased likelihood of dialysis requirement (adjusted odds ratio [OR], 2.36 [95% CI, 1.87-2.99]), dialysis dependence (adjusted OR, 1.89 [95% CI, 2.53-1.34]), and in-hospital mortality (adjusted OR, 1.34 [95% CI, 1.01-1.34]). Conclusions Increased NT-proBNP was associated with an increased risk of dialysis requirement, becoming dialysis dependent, and in-hospital mortality in patients with moderate-to-severe acute kidney injury.


[Use of x-ray endovascular occlusion in combined treatment of juvenile angiofibroma of the skull base in children].
Of a total of 103 patients with juvenile angiofibroma of the base of the skull surgical treatment was given to 98 children. 10 operations were performed after preoperative roentgeno-endovascular occlusion (REO) of the tumor afferent vessels. Such occlusion in the region of a maxillaris was a sufficient measure to warrant a 2-fold reduction in the intraoperative blood loss and was achieved with hydrogel spheres and cylinders 0.4-0.6 mm in diameter. 4 days are an optimal time for operative intervention after the REO. The nasomaxillary approach was used in most cases preceded by diagnostic carotid angiography in the frontal and lateral views. No complications arose due either to the angiography or REO. The latter was found beneficial when performed prior to surgical intervention for juvenile angiofibroma of the base of the skull.


A facile approach for thermal and reduction dual-responsive prodrug nanogels for intracellular doxorubicin delivery.
In this study, thermal and redox dual sensitive nanogels based on N-vinylcaprolactam (VCL) and N-succinimidyl methacrylate (Suma) crosslinked with diallyl disulfide were synthesized via a facile and straightforward method. The reactive succinimide groups were mainly located in the nanogel shell which increases considerably their accessibility for conjugation reactions. Doxorubicin (DOX) was successfully loaded into the nanogel through two different routes. Approximately 91.3% of DOX molecules were covalently bound to the nanogel network via coupling with succinimide groups under mild conditions to obtain prodrug nanogels, while 8.7% of DOX molecules were captured into the nanogels via electrostatic interactions with the -COOH group from the hydrolyzed ester groups of the nanogels. The DOX-loaded nanogels demonstrated volume phase transition temperature (VPTT) near human physiological temperature. The nanogels shrink near body temperature, which could help lock the drug molecules stably in blood circulation. The conjugation of DOX molecules in nanogels avoided premature unspecific drug release under physiological conditions. The small amount of physically loaded DOX (due to electrostatic interactions) could be partially released as free DOX due to the increasing acidic conditions in the endosome/lysosome pathway. The chemically conjugated DOX was released in the form of a prodrug polymer triggered by the high concentration of glutathione in the cytosol that induced nanogel degradation. The present drug delivery system exhibits a sustainable delivery profile in the intracellular release study and high antitumor activity. We are convinced that the thermal and reduction dual-responsive prodrug nanogels have tremendous potential in controlled drug release.


Psychosocial wellbeing shortly after allocation to a freeze-all strategy compared with a fresh transfer strategy in women and men: a sub-study of a randomized controlled trial.
Is the psychosocial wellbeing affected in women and men shortly after allocation to a freeze-all strategy with postponement of embryo transfer compared to a fresh transfer strategy? In general, psychosocial wellbeing (i.e. emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit) was similar in women and men allocated to a freeze-all versus those allocated to a fresh-transfer strategy 6 days after disclosure of treatment strategy (i.e. 4 days after oocyte retrieval), although women in the freeze-all group reported a slightly higher degree of depressive symptoms and mood swings compared to women in the fresh transfer group. The use of a freeze-all strategy, i.e. freezing of the entire embryo cohort followed by elective frozen embryo transfer in subsequent cycles has increased steadily over the past decade in assisted reproductive technology (ART). This strategy essentially eliminates the risk of ovarian hyperstimulation syndrome and has proven beneficial regarding some reproductive outcomes in subgroups of women. However, patients experience a longer time interval between oocyte retrieval and embryo transfer, hence a longer time to pregnancy, possibly adding additional stress to the ART treatment. So far, little focus has been on the possible psychosocial strains caused by postponement of embryo transfer. This is a self-reported questionnaire based sub-study of a multicentre randomized controlled trial (RCT) including 460 women and 396 male partners initiating their first, second, or third treatment cycle of invitro fertilisation or intracytoplasmic sperm injection (ICSI) from May 2016 to September 2018. This sub-study was included in the primary project protocol and project plan for the RCT, as psychosocial wellbeing was considered a secondary outcome. Women from eight public fertility clinics in Denmark and Sweden and one private clinic in Spain were randomized in a 1:1 ratio on the day of inclusion (menstrual cycle day 2 or 3) to either a freeze-all strategy with postponement of embryo transfer to a subsequent modified natural menstrual cycle or a fresh transfer strategy with embryo transfer in the hormone stimulated cycle. Treatment allocation was blinded until the day of the ovulation trigger. Women and their male partners were asked to complete a validated self-reported questionnaire 6 days after unblinding of treatment group allocation, corresponding to 4 days after oocyte retrieval, investigating their psychosocial wellbeing related to the treatment defined as emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit. The questionnaire included items from the Copenhagen Multi-Centre Psychosocial Infertility (COMPI) Fertility Problem Stress Scales and the COMPI Marital Benefit Measure. Baseline characteristics were comparable between the two groups for both women and men. In total, response rates were 90.7% for women and 90.2% for men. In the freeze-all group, 207 women and 179 men completed the questionnaire compared with 204 women and 178 men in the fresh transfer group. Men in the two treatment groups did not differ in any of the explored aspects of psychosocial wellbeing (i.e. emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit) 6 days after disclosure of treatment strategy. Women in the freeze-all group reported a slightly higher degree of depressive symptoms (P = 0.045) and mood swings (P = 0.001) (i.e. variables included in 'emotional reactions to treatment') compared to women in the fresh transfer group. When adjusted for multiple testing, depressive symptoms were no longer significantly different between the two groups. No additional differences in psychosocial wellbeing were found. Self-reported quality-of-life during treatment was also rated as similar between the two groups in both women and men, but was slightly lower than they would rate their quality-of-life when not in fertility treatment. Although response rates were high, selection bias cannot be excluded. As this study was an RCT, we assume that psychosocial characteristics of the participants were equally distributed in the two groups, thus it is unlikely that the identified psychosocial differences between the freeze-all and fresh transfer group were present already at baseline. Furthermore, the questionnaire was completed as a one-time assessment 4 days after oocyte retrieval, thus not reflecting the whole treatment process, whereas an assessment after the full completed treatment cycle is needed to draw firm conclusions about the psychosocial consequences of the whole waiting period. However, a question posted that late would be highly biased on whether or not a pregnancy had been achieved. The results indicate that individuals in the freeze-all group exhibited slightly higher levels of depressive symptoms and mood swings compared to those in the fresh transfer group. Nevertheless, it is important to note that any worries related to potential emotional strains stemming from delaying embryo transfer should not overshadow the adoption of a freeze-all approach in cases where it is clinically recommended. As long as patients are provided with comprehensive information about the treatment strategy before initiating the process, it is worth emphasising that other aspects of psychosocial wellbeing were comparable between the two groups. The study is part of the Reprounion collaborative study, co-financed by the European Union, Interreg V Öresund-Kattegat-Skagerrak. L.P. reports financial support from Merck A/S. H.S.N. reports grants from Freya Biosciences ApS, Ferring Pharmaceuticals, BioInnovation Institute, Ministry of Education, Novo Nordic Foundation, Augustinus Fonden, Oda og Hans Svenningsens Fond, Demant Fonden, Ole Kirks Fond and Independent Research Fund Denmark and personal fees from Ferring Pharmaceuticals, Merck A/S, Astra Zeneca, Cook Medical, IBSA Nordic and Gedeon Richter. H.S.N is founder and chairman of the Maternity Foundation and co-developed the Safe Delivery App (non-profit). N.C.F. reports grants from Gedeon Richter, Merck A/S, Cryos International and financial support from Ferring Pharmaceuticals, Merck A/S and Gedeon Richter. N.C.F. is chairman in the steering committee for the guideline groups for The Danish Fertility Society (non-profit). P.H. reports honoraria from Merch A/S, IBSA Nordic and Gedeon Richter. A.L.M.E. reports grants and financial support from Merck A/S and Gedeon Richter. A.P. reports grants from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S and personal fees from Preglem S.A., Novo Nordic Foundation, Ferring Pharmaceuticals, Gedeon Richter, Cryos International, Merch A/S, Theramex and Organon and the lend of embryoscope to the institution from Gedeon Richter. All other authors declare no conflict of interest. Clinicaltrials.gov NCT02746562.


RNA-seq analysis revealed genes associated with neuropathic pain induced by chronic compressive injury in interferon regulatory factors 4 knockout mice.
To explore the differential expression of genes between wild-type chronic compressive injury (CCI) mice (WT-CCI) and interferon regulatory factors 4 (IRF4) knockout CCI mice (KO-CCI) by RNA-seq analysis of the mouse spinal cord. RNA-seq analysis of the spinal cord tissue of the chronic sciatic nerve ligation mice and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used. A total of 104 genes were up-regulated and 116 genes were down-regulated in spinal cord of the mice in IRF4 knockout (KO-CCI) group compared with that in the wild-type CCI (WT-CCI) group. There were 1472 differentially expressed genes in the biological process group, 62 differentially expressed genes in the cellular component group, and 163 differentially expressed genes in the molecular function group in KO-CCI mice. A total of 14 genes related to inflammatory reactions were differentially expressed. Real-time PCR results confirmed that Pparg and Grpr mRNA expression was up-regulated and Arg 1 and Ccl11 mRNA expression was down-regulated in the KO-CCI group. IRF4 is involved in neuropathic pain in CCI mice, IRF4 may participate in neuropathic pain by regulating Grpr, Mas1, Galr3, Nos2, Arg1, Ccl11, Ptgs2, S100a8, Pparg, Cd40, Has2, Gpr151, Il123a, Capns2, Ankrd1, Ccnb1, and Nppb genes.


Clearance of ethylene glycol by kidneys and hemodialysis.
A patient with acute ethylene glycol poisoning was treated with ethanol administration and hemodialysis, and his renal function remained consistently normal. Serial measurements of serum and urine levels of urea, creatinine, ethylene glycol, and ethanol were performed to compare the relative contributions of the hemodialyzer and the patient's kidneys in clearing ethylene glycol from the blood. Simultaneous measurements of the serum-osmolal gap (corrected for ethanol) and anion gap were correlated with these data. Mean renal clearance of ethylene glycol was 27.5 +/- 4.1 ml/min, with a fractional ethylene glycol excretion of 19.8 +/- 1.5%. This was lower than the mean urea clearance of 89.4 +/- 11.0 ml/min and fractional urea excretion of 66.0 +/- 7.8%. Hemodialyzer clearance of ethylene glycol was 156 ml/min. There was a nearly exact correlation between the serum ethylene glycol level and the corrected osmolal gap (r = 0.998, p less than 0.01). The calculated renal elimination half-life of ethylene glycol was 18 hr. We conclude that with a moderate diuresis, the normal human kidney contributes significantly to the removal of ethylene glycol from the blood. Corrected serum osmolal gap provides a nearly exact approximation of the serum ethylene glycol level and is a useful therapeutic guide.


Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in natto, a Japanese traditional fermented food.
Angiotensin I converting enzyme (ACE) was inhibited by the culture medium of Bacillus subtilis subsp. natto, which ferments boiled soy beans to natto, a Japanese traditional food. Subtilisin NAT (nattokinase) produced by B. subtilis also inhibited ACE, and the inhibition was markedly stimulated by heat treatment of subtilisin at 120 °C for 15 min. Inhibition of ACE by subtilisin was of a mixed type: the decrease in V(max) and the increase in K(m) value. SDS-polyacrylamide gel electrophoresis showed that heat treatment of subtilisin caused inactivation with fragmentation of the enzyme protein into small peptides. The inhibitory action of subtilisin was not due to an enzymatic action of protease, but may be ascribed to the potent ACE-inhibitory peptides such as LY and FY, amino acid sequences in subtilisin. HPLC-MS analysis of heat-inactivated subtilisin confirmed that LY and FY were liberated by fragmentation of the enzyme. Inhibition of ACE by subtilisin and its degradation peptides such as LY and FY may participate in the suppression of blood pressure by ingestion of natto.


Patterns in randomly evolving networks: idiotypic networks.
We present a model for the evolution of networks of occupied sites on undirected regular graphs. At every iteration step in a parallel update, I randomly chosen empty sites are occupied and occupied sites having occupied neighbor degree outside of a given interval (t(l),t(u)) are set empty. Depending on the influx I and the values of both lower threshold and upper threshold of the occupied neighbor degree, different kinds of behavior can be observed. In certain regimes stable long-living patterns appear. We distinguish two types of patterns: static patterns arising on graphs with low connectivity and dynamic patterns found on high connectivity graphs. Increasing I patterns become unstable and transitions between almost stable patterns, interrupted by disordered phases, occur. For still larger I the lifetime of occupied sites becomes very small and network structures are dominated by randomness. We develop methods to analyze the nature and dynamics of these network patterns, give a statistical description of defects and fluctuations around them, and elucidate the transitions between different patterns. Results and methods presented can be applied to a variety of problems in different fields and a broad class of graphs. Aiming chiefly at the modeling of functional networks of interacting antibodies and B cells of the immune system (idiotypic networks), we focus on a class of graphs constructed by bit chains. The biological relevance of the patterns and possible operational modes of idiotypic networks are discussed.


Acquired von Willebrand syndrome in a myeloproliferative disorder. Case 6.
We present a woman (age: 57 years) with an excessive bleeding episode under acetylsalicylic acid after bone marrow puncture due to an acquired von Willebrand syndrome (avWS) in the context of a myeloproliferative disorder. The laboratory features showed a high platelet concentration and a qualitative defect of von Willebrand factor (vWF) with a low normal vWF ristocetin cofactor activity, a normal vWF antigen and a decrease of the larger vWF multimers in plasma. The exact mechanism of avWS is still incompletely resolved. Myeloproliferative diseases are one of several underlying disorders that may cause avWS. The diagnosis of the underlying disease is important because its treatment may lead to an improvement of the vWF abnormality. For symptomatic treatment of bleeding, desmopressin, vWF concentrate infusion, intravenous immunoglobulin and/or fibrinolysis inhibitors can be tried.


[Smoking among military personnel of young age: bad habit and risk factor].
Anonymous questioning was done among military personnel to study their attitude to healthy way of living and smoking. 80 military persons aged from 18 till 30 participated in the study (40 officers and 40 soldiers). Obtained results showed that 72,5% of soldiers and 42,5% of officers smoked it in connection with compromised heredity may lead to the development of chronic non-infectious disease. Military personnel realize their own responsibility in relation to their health and have all necessary knowledge of healthy way of living but apply their knowledge not in full extent to maintain and strengthen their health. Revealed discrepancy shows that military personnel underestimate bad effect of smoking on health. It necessitates enhancing sanitary and educational measures and individual responsibility of military personal toward their health and providing influence on motivation to lead healthy way of living.


Identification and characterization of a novel retinoic acid response element in zebrafish cyp26a1 promoter.
Cyp26A1 is a major enzyme that controls retinoic acid (RA) homeostasis by metabolizing RA into bio-inactive metabolites. Previously, we demonstrated that zebrafish cyp26a1 promoter possesses two conserved RA response elements (RAREs; proximal R1 and distal R2) in response to RA. Here, we report that it contains a novel RARE (R3) lying between R1 and R2. Mutagenesis analysis reveals that R3 works together with R1 and R2 to ensure the maximum RA inducibility of cyp26a1 promoter. Performing electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we show that RA receptor alpha can bind the novel RARE. Creating and analyzing transgenic zebrafish of Tg(cyp26a1-R3mut:eYFP)nju3/+ that harbor enhanced yellow fluorescent protein reporter gene (eYFP) driven by cyp26a1 promoter with mutated R3, we demonstrate that the reporter is mainly expressed in tissues of endogenous RA independent but not regions of RA dependent. Like Tg(cyp26a1:eYFP)nju1/+, which harbor eYFP driven by wild-type cyp26a1 promoter, the reporter in Tg(cyp26a1-R3mut:eYFP)nju3/+ responds to excessive RA dose dependently. However, it is expressed in a significantly lower level than the reporter in Tg(cyp26a1:eYFP)nju1/+ in response to exogenous RA. Taken together, our results demonstrate that zebrafish cyp26a1 promoter contains a novel RARE that plays crucial roles in regulating cyp26a1 expression during early development of zebrafish.


CTCF and Cohesin in Genome Folding and Transcriptional Gene Regulation.
Genome function, replication, integrity, and propagation rely on the dynamic structural organization of chromosomes during the cell cycle. Genome folding in interphase provides regulatory segmentation for appropriate transcriptional control, facilitates ordered genome replication, and contributes to genome integrity by limiting illegitimate recombination. Here, we review recent high-resolution chromosome conformation capture and functional studies that have informed models of the spatial and regulatory compartmentalization of mammalian genomes, and discuss mechanistic models for how CTCF and cohesin control the functional architecture of mammalian chromosomes.


Bronchial length behavior with respect to lung volume histories in different bronchial sizes in excised dog lungs.
The bronchial length behavior of three different-sized segments in seven excised dog lobes was examined in terms of the transpulmonary pressure (PL)-bronchial length relationship and the absolute lung volume (VL)-bronchial length relationship during lung inflation and deflation. The straight bronchi of the right lower lobes were used and the bronchial lengths were measured directly and continuously with a linear displacement transducer which was connected by a thin rod to a wedged bead in the bronchi. From PL 30 to 0 cmH2O, the lengths of proximal, intermediate and distal bronchi from the airway opening decreased by 25.2 +/- 4.0%; 36.5 +/- 10.4%; and 37.0 +/- 11.5% (mean +/- S.D.), respectively. Hysteresis of bronchial length existed in the lung volume histories at the same PL, but not at the same VL. With deflation of lung from PL 30 to 0 cmH2O, the more proximal bronchi less changed their length disproportionately with lung volume. It is suggested that nonhomogeneous expansion between lung parenchyma and the bronchi would be more intense in the proximal bronchi than the distal bronchi in terms of bronchial length.


Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans.
Dietary consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against cardiometabolic disease through modulation of systemic and adipose inflammation. However, it is often difficult to detect the subtle effects of n-3 PUFA on inflammatory biomarkers in traditional intervention studies. We aimed to identify novel n-3 PUFA modulated gene expression using unbiased adipose transcriptomics during evoked endotoxemia in a clinical trial of n-3 PUFA supplementation. We analyzed adipose gene expression using RNA sequencing in the fenofibrate and omega-3 fatty acid modulation of endotoxemia (FFAME) trial of healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=8; 3600mg/day EPA/DHA) for 6weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (lipopolysaccharide 0.6ng/kg i.v.). As expected, supplementation with n-3 PUFA vs. placebo alone had only modest effects on adipose tissue gene expression, e.g., increased expression of immediate early response IER2. In contrast, the transcriptomic response to evoked endotoxemia was significantly modified by n-3 PUFA supplementation, with several genes demonstrating significant n-3 PUFA gene-nutrient interactions, e.g., enhanced transcriptional responses in specific immune genes IER5L, HES1, IL1RN, CCL18, IL1RN, IL7R, IL8, CCL3 and others. These data highlight potential mechanisms whereby n-3 PUFA consumption may enhance the immune response to an inflammatory challenge. In conclusion, unbiased transcriptomics during evoked inflammation reveals novel immune modulating functions of n-3 PUFA nutritional intervention in a dynamic pathophysiological setting.


Disparities in Health Supervision for Children With Down Syndrome.
Increasing evidence suggests children with Down syndrome do not receive recommended health care services. We retrospectively assessed adherence to the 2001 American Academy of Pediatrics health supervision guidelines for 124 children with Down syndrome. Cervical spine radiographs were completed for 94% of children, often preoperatively. Adherence to complete blood count recommendations was 55% (95% CI 44% to 66%); lower for males ( P = .01) and children with private medical insurance ( P = .04). Adherence to thyroid function recommendations was 61% (95% CI 54% to 67%); higher for children seen by a pediatrician ( P = .002) and with known thyroid disease ( P < .0001). Adherence to audiology and ophthalmology recommendations was 33% (95% CI 27% to 40%) and 43% (95% CI 37% to 50%), respectively. Adherence rates were higher for children referred to an otolaryngologist ( P = .0002) and with known eye disease ( P < .0001). Future efforts should identify barriers to care and improve adherence to recommended screening.


Spinal fusion and total hip arthroplasty: why timing is important.
There is increasing debate among orthopaedic surgeons over the temporal relationship between lumbar spinal fusion (LSF) and total hip arthroplasty (THA) for patients with hip-spine syndrome. Few large studies have directly compared the results of patients who undergo LSF prior to THA (LSF-THA) to those who undergo LSF after THA (THA-LSF). The current study matched THA patients with a prior LSF to patients who underwent LSF after THA to assess: 90-day and 1-year (1) medical/surgical complications; and (2) revisions. We queried a national, all-payer database to identify all patients undergoing THA between 2010 and 2018 (n = 716,084). The LSF-THA patients and THA-LSF patients were then matched 1:1 on age, sex, Charleson Comorbidity Index, and obesity. Medical/surgical complications and revisions at 90 days and 1 year were recorded. Categorical and continuous variables were analysed utilising t-tests and chi-square, respectively. LSF-THA patients experienced significantly more postoperative dislocations at 90 days and 1 year compared to THA-LSF patients (p = 0.048 and p < 0.001). There were a similar number of revisions performed for LSF-THA and THA-LSF patients at both 90 days and 1 year (p = 0.183 and p = 0.426). Furthermore, at 1 year, LSF-THA patients experienced more pneumonia (p = 0.005) and joint infection (p = 0.020). Prior LSF has been demonstrated to increase the risk of postoperative dislocation in patients undergoing THA. The results of the present study demonstrate increased dislocations with LSF-THA compared to THA-LSF. For "hip spine syndrome" patients requiring both LSF and THA, it may be more beneficial to undergo THA prior to LSF. Arthroplasty surgeons may wish to collaborate with spinal surgeons to ensure optimal outcomes for this group of patients.


Acetaminophen ototoxicity after acetaminophen/hydrocodone abuse: evidence from two parallel in vitro mouse models.
Acetaminophen/hydrocodone, a commonly used analgesic preparation, has been linked to rapidly progressing sensorineural hearing loss in human patients. The cellular and molecular mechanisms underlying the ototoxic effects of this drug combination are currently unknown, but are usually associated with high doses of hydrocodone. This study was aimed at identifying the specific agent responsible for hearing loss from toxic killing of cochlear sensory cells. Dose-response study. University laboratory and private research facility. Math1 green fluorescent protein neonatal mouse cochlear cultures as well as a mouse auditory cell line (HEI-OC1) were exposed in vitro to different concentrations of acetaminophen, hydromorphone (the active metabolite of hydrocodone), and the micronutrient L-carnitine, either alone or combined. Using fluorescent and light microscopy, we quantified the sensory hair cells from a 600-microm basal segment before and after treatment. Acetaminophen/hydrocodone-induced apoptosis of HEI-OC1 was evaluated by caspase 3-activation studies. Statistically significant cell survival was determined with Student t test and analysis of variance. Cell death was associated mainly with exposure to acetaminophen, was slightly potentiated when combined with hydromorphone, and was partially prevented by L-carnitine. Exposure to hydrocodone or hydromorphone alone failed to kill either cochlear hair cells or HEI-OC1 cells. Our findings point to acetaminophen, rather than hydrocodone, as the primary cytotoxic agent. Hydrocodone, however, may work synergistically with acetaminophen, increasing the damage to auditory cells. These findings are an important first step toward understanding the mechanism of acetaminophen/hydrocodone ototoxicity and may lead to future treatment strategies for hearing loss from ototoxic medications.


Real-Time detection and mixing state of methanesulfonate in single particles at an inland urban location during a phytoplankton bloom.
Dimethyl sulfide (DMS), produced by oceanic phytoplankton, is oxidized to form methanesulfonic acid (MSA) and sulfate, which influence particle chemistry and hygroscopicity. Unlike sulfate, MSA has no known anthropogenic source making it a useful tracer for ocean-derived biogenic sulfur. Despite numerous observations of MSA, predominately in marine environments, the production pathways of MSA have remained elusive highlighting the need for additional measurements, particularly at inland locations. During the Study of Organic Aerosols in Riverside, CA from July-August 2005, MSA was detected in submicrometer and supermicrometer particles using real-time, single-particle mass spectrometry. MSA was detected due to blooms of DMS-producing organisms along the California coast. The detection of MSA depended on both the origin of the sampled air mass as well as the concentration of oceanic chlorophyll present. MSA was mainly mixed with coastally emitted particle types implying that partitioning of MSA occurred before transport to Riverside. Importantly, particles containing vanadium had elevated levels of MSA compared to particles not containing vanadium, suggesting a possible catalytic role of vanadium in MSA formation. This study demonstrates how anthropogenic, metal-containing aerosols can enhance the atmospheric processing of biogenic emissions, which needs to be considered when modeling coastal as well as urban locations.


Comprehensive review of the functional outcome evaluation of clubfoot treatment: a preferred methodology.
Treatment outcome has been a focus of interest in those who manage clubfeet. Because of a lack of a common evaluation protocol, it has become necessary to establish a universally recognized quantitative measurement to compare and better understand the treatment outcome. The outcome is not merely morphological and radiographic, but it should also include functional and quality-of-life measurements. In this article, we will outline the most commonly used methods of long-term evaluation for congenital clubfeet and recommend the data collection parameters that are most appropriate for a comprehensive functional analysis. This will begin with pretreatment classifications that are important in prognosticating the results. The physical examinations and plain radiographs in standing position are also two fundamental evaluations of clubfoot. Several outcome evaluations have been published in the literature and may be useful depending on the desired metrics. Gait analysis is an additional useful technical tool for analyzing the motion of the foot and ankle and its relation to the whole body function; pedobarography added to the dynamics of the evaluation. Functional quality-of-life questionnaires are increasing in popularity for measuring the total body functional status and the quality of life.


Interobserver and Intraobserver Agreements of the Detection of Demodex Infestation by in Vivo Confocal Microscopy.
The purpose of the study was to determine interobserver and intraobserver agreement, repeatability, and intrasubject variation of the detection of Demodex infestation in eyelids of blepharitis patients using in vivo confocal microscopy (IVCM). Eighty-three eyes of 42 blepharitis patients were included in the study. All eyelids were evaluated from temporal to nasal with IVCM using section mode and 10 lashes with their follicles were imagined, and every image with suspicion of Demodex infestation was recorded. Two experienced and two inexperienced ophthalmologists were masked for the diagnosis and interpreted the IVCM images regarding the presence of Demodex infestation with a 3-week interval. Interobserver and intraobserver agreements were calculated with Cohen's kappa and its variant statistics between and within experienced observers and between inexperienced observers. While average sensitivity for the diagnosis of demodicosis in IVCM images was 83.35% for experienced and 51.35% for inexperienced observers, the average positive predictive value was 88.6% for experienced observers and 91.05% for inexperienced ones. Interobserver agreement between experienced observers was moderate (κ = 0.529) and intraobserver agreements within experienced observers were perfect (κ = 0.918 for observer-1; κ = 0.958 for observer-2). Interobserver agreement between inexperienced observers was poor (κ = 0.162) and intraobserver agreements within inexperienced observers were fair (κ = 0.427 for observer-3; κ = 0.475 for observer-4). The sensitivity, interobserver and intraobserver agreements in IVCM image analysis for the detection of Demodex infestation were highly associated with the clinical experience on IVCM imaging. In the hands of an experienced clinician, IVCM could be reliable for the diagnosis of ocular demodicosis.


Induction of Survival of Motor Neuron (SMN) Protein Deficiency in Spinal Astrocytes by Small Interfering RNA as an In Vitro Model of Spinal Muscular Atrophy.
Spinal muscular atrophy (SMA) is a motor neuron disorder leading to progressive loss of ventral horn neurons resulting in muscle wasting. Here we investigate the contribution of spinal astrocytes to the pathogenesis of late-onset SMA forms using a mouse model. Furthermore, we generated SMA-like astrocytes using survival of motor neuron (SMN) siRNA transfection techniques. In the SMA mouse model, the activation of spinal astrocytes and the reduction of the inward rectifier potassium channel Kir4.1 and excitatory amino acid transporter 1 (EAAT1) were observed at postnatal day (P) 28, preceding the loss of spinal motor neurons appearing earliest at P42. Using SMA-like astrocytes, we could mimic the modulation of spinal astrocytes of the mouse model in a dish and perform electrophysiological assessments and functional assays. In SMA-like astrocytes, glutamate uptake was diminished due to a reduction in EAAT1. Furthermore, patch-clamp measurements revealed reduced potassium uptake into astrocytes with membrane depolarization. Additionally, exposure of healthy spinal motor neurons to a conditioned medium of SMA-like astrocytes resulted in increased firing frequency. These data demonstrate spinal astrocytes' crucial role in the late-onset SMA forms' pathogenesis.


A genome-scale metabolic model accurately predicts fluxes in central carbon metabolism under stress conditions.
Flux is a key measure of the metabolic phenotype. Recently, complete (genome-scale) metabolic network models have been established for Arabidopsis (Arabidopsis thaliana), and flux distributions have been predicted using constraints-based modeling and optimization algorithms such as linear programming. While these models are useful for investigating possible flux states under different metabolic scenarios, it is not clear how close the predicted flux distributions are to those occurring in vivo. To address this, fluxes were predicted for heterotrophic Arabidopsis cells and compared with fluxes estimated in parallel by (13)C-metabolic flux analysis (MFA). Reactions of the central carbon metabolic network (glycolysis, the oxidative pentose phosphate pathway, and the tricarboxylic acid [TCA] cycle) were independently analyzed by the two approaches. Net fluxes in glycolysis and the TCA cycle were predicted accurately from the genome-scale model, whereas the oxidative pentose phosphate pathway was poorly predicted. MFA showed that increased temperature and hyperosmotic stress, which altered cell growth, also affected the intracellular flux distribution. Under both conditions, the genome-scale model was able to predict both the direction and magnitude of the changes in flux: namely, increased TCA cycle and decreased phosphoenolpyruvate carboxylase flux at high temperature and a general decrease in fluxes under hyperosmotic stress. MFA also revealed a 3-fold reduction in carbon-use efficiency at the higher temperature. It is concluded that constraints-based genome-scale modeling can be used to predict flux changes in central carbon metabolism under stress conditions.


Mesenteric malignant lymphoma detected with routine color Doppler ultrasonography.
This report concerns a case of primary mesenteric malignant lymphoma detected with routine color Doppler ultrasonography. When a 44-year-old man underwent a first-time medical checkup, ultrasonographic imaging and computed tomography showed the presence of a large tumor measuring about 8 cm in transverse diameter. Color Doppler ultrasonography identified the characteristic vessel structure of a nodal lesion, namely, a hilar vessel, a curved section of the central vessel together with peripheral branches, and focal absence of perfusion in a hypoechoic imaging of the left periumbilical area. These findings contributed to the diagnosis of a malignant lymphoma and the surgical treatment of the tumor was successful.


Sewage treatment by controlled eutrophication: bacterial study.
Several groups of bacteria were isolated and identified in an evaluation of the microbiological properties of a sewage treatment system involving the process of controlled eutrophication in a marine setting (J. G. Songer, N. M. Trieff, R. F. Smith, and D. Grajcer, 1974). Fecal coliforms, enterococci, Salmonellae, Shigellae, Vibrio parahaemolyticus, and Vibrio alginolyticus were studied at three stages of the treatment process. Significant reductions in fecal coliforms (P < 0.01) and enterococci (P < 0.01) were noted from raw sewage to effluent. Salmonellae and Shigellae were not detected at any stage, nor was V. parahaemolyticus. V. alginolyticus was isolated from the effluent only, reflecting the halophilic nature of the organism; low concentrations in raw sewage increased in the more saline effluent. Brine shrimp (Artemia salina), the herbivores in this system, were tested and found to have extremely low numbers of the organisms under study associated with them. Findings point further toward the use of this system as a combined mariculture-sewage treatment facility.


Single-cell analysis and spatial resolution of the gut microbiome.
Over the past decade it has become clear that various aspects of host physiology, metabolism, and immunity are intimately associated with the microbiome and its interactions with the host. Specifically, the gut microbiome composition and function has been shown to play a critical role in the etiology of different intestinal and extra-intestinal diseases. While attempts to identify a common pattern of microbial dysbiosis linked with these diseases have failed, multiple studies show that bacterial communities in the gut are spatially organized and that disrupted spatial organization of the gut microbiome is often a common underlying feature of disease pathogenesis. As a result, focus over the last few years has shifted from analyzing the diversity of gut microbiome by sequencing of the entire microbial community, towards understanding the gut microbiome in spatial context. Defining the composition and spatial heterogeneity of the microbiome is critical to facilitate further understanding of the gut microbiome ecology. Development in single cell genomics approach has advanced our understanding of microbial community structure, however, limitations in approaches exist. Single cell genomics is a very powerful and rapidly growing field, primarily used to identify the genetic composition of microbes. A major challenge is to isolate single cells for genomic analyses. This review summarizes the different approaches to study microbial genomes at single-cell resolution. We will review new techniques for microbial single cell sequencing and summarize how these techniques can be applied broadly to answer many questions related to the microbiome composition and spatial heterogeneity. These methods can be used to fill the gaps in our understanding of microbial communities.


Antibody-dependent cytolysis of the human leukemia cell line K-562 in the absence of effector cells or complement.
K-562 human leukemia cells grown in the presence of specific goat anti-K-562 gamma globulin, F(ab)'2, Fab', or Fab showed a decrease in DNA and protein syntheses and a loss of cell viability within several hours. Eventually all cells died and lysed within 2-5 days. These events occurred in the absence of added effector cells or complement. The effect on the cell was not due to proteolytic or other external lytic activity generated at the cell surface, since 51Cr-labeled bystander cells or antibody-sensitized bystander cells (chicken erythrocytes or K-562 cells) were not lysed when added to cultures of K-562 cells incubated with immune globulin. The anti-K-562 gamma globulin was not observed to patch or cap on K-562 cells, but the ability of bound immunoglobulin to fix complement decreased markedly (50% in 60 min), so that no complement-mediated cytolysis could be observed at 2 hr. However, the immunoglobulin, at least portions of it, reacted with fluorescein--labeled rabbit anti-goat gamma globulin for about 16 hr. 125I-labeled immune globulin appeared to be internalized and released into the medium as small degradation products. 125I-labeled Fab did not appear to be internalized, since it was released intact and more rapidly from cells than the intact globulin.


Prevalence of anterior knee pain after patellar retention total knee arthroplasty: Comparison of patients with rheumatoid arthritis versus primary osteoarthritis.
The aim of this study was to investigate whether there is an increased risk of anterior knee pain (AKP) after total knee arthroplasty (TKA) without patellar resurfacing in patients with rheumatoid arthritis (RA) versus primary osteoarthritis (OA). This study was a retrospective review of 388 patients (577 knees) who underwent TKA without patellar resurfacing between 2003 and 2011, with a minimum of 5 years of follow-up. Patients were divided into two groups: Group OA (273 knees of 206 patients; 83 males, 123 females; mean age: 64.4 (47-87) years) and Group RA (304 knees of 182 patients; 92 males, 90 females; mean age: 50.7 (21-72) years). In the clinical evaluation, the knee range of motion (ROM) and several outcome measures such as The Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and International Knee Documentation Committee (IKDC) scores were used preoperatively and at the final follow-up visit. The quality of life was measured using Short Form (SF)-36 MCS and PCS scores. The primary outcome was the frequency and severity of patient-reported AKP. The AKP Scale was used to determine the severity of AKP. The IKDC raised from 21.62 (range, 13-29.9) preoperatively to 85.1 (range, 80-88) for group OA and from 21.8 (range, 13-29.9) to 85.2 (range, 81-88) for group RA (p < 0.001). The mean KSS improved from 28.35 (range, 22-38) preoperatively to 90.04 (range, 88-95) for group OA and from 21.9 (range, 18-35) preoperatively to 89.7 (range, 86-95) for group RA. The mean WOMAC increased from 20.61 (range, 17.4-24.2) preoperatively to 95.7 (range, 90.9-97.7) for group OA (p < 0.001) and from 20.2 (range, 16.7-24.2) preoperatively to 95.8 (range, 90.9-98.5) for group RA (p < 0.001). The mean ROM improved from 80.14° (range, 55°-130°) preoperatively to 113.17° (range, 95°-140°) in group OA (P = 0.003) and from 73.4° (range, 10°-130°) to 112.8° (range 90°-140°) in group RA (P = 0.003) postoperatively. The frequency of AKP was 8% in Group OA and 7% in Group RA (p = 0.27). For patients with AKP, the mean AKP Scale was 92.74 (range, 84-98) in Group OA and 93.39 (range, 82-98) in Group RA (p = 0.3). After TKA without resurfacing the patella, patients with RA were determined to have a similar risk for AKP as those with OA. Level III, Therapeutic Study.


[Basic epidemiological indices for congenital aural atresia in Sakha-Yakutia].
Prevalence of congenital aural atresia (CAA) was studied in pediatric population of Republic Sakha Sakha-Yakutia. The diagnosis of CAA was made in 118 patients born in 1984-2004. CAA morbidity in children of Yakutia depended on national identity: overall morbidity was 3.1, in Yakuts - 5.3, in Russians - 1.9 per 10 000 newborns. CAA prevalence corresponded to ethnoterritorial characteristics of population. The highest prevalence occurred in the Arktic region (7.5 per 10,000), the lowest one - in Industrial region (0.24 per 10,000).


Expectation of success following noncontingent punishment in introverts and extraverts.
Recent findings indicate that extraverts are more likely than introverts to continue responding in the face of punishment and frustrating nonreward (Newman & Kosson, 1984; Tiggemann, Winefield, & Brebner, 1982). The current study investigates whether extraverts' expectations for success are, similarly, resistant to interruption and alteration. To test this hypothesis, 50 introverted and 50 extraverted male undergraduates were exposed to pretreatment with either a 50% level of noncontingent reward or a 50% level of noncontingent punishment. As predicted, there were significant Group X Pretreatment interactions on all dependent measures. In comparison to those introverts who received the punishment pretreatment, extraverts exposed to the same pretreatment placed larger wagers on their ability to succeed, and reported higher levels of perceived control. In addition, relative to their estimates for the pretreatment task, extraverts exposed to noncontingent punishment increased their expectation for success, whereas introverts exposed to noncontingent punishment decreased their performance expectations. No differences were observed between the two groups following pretreatment with noncontingent reward. The results suggest that extraverts are characterized by a distinctive reaction to punishment involving response facilitation as opposed to response inhibition.


Inhibition of N-myc expression and induction of apoptosis by iron chelation in human neuroblastoma cells.
Neuroblastoma is the second most common solid malignancy of childhood. Enhanced expression of the amplified N-myc gene in the tumor cells may be associated with poor patient prognosis and may contribute to tumor development and progression. The use of deferoxamine mesylate (DFO), an iron chelator, to treat neuroblastoma is being investigated in national clinical studies. We show here by TUNEL assay and DNA laddering that DFO induces apoptosis in cultured human neuroblastoma cells, which is preceded by a decrease in the expression of N-myc and the altered expression of some other oncogenes (up-regulating c-fos and down-regulating c-myb) but not housekeeping genes. The decrease in N-myc expression is iron-specific but does not result from inhibition of ribonucleotide reductase, because specific inhibition of this iron-containing enzyme by hydroxyurea does not affect N-myc protein levels. Nuclear run-on and transient reporter gene expression experiments show that the decrease in N-myc expression occurs at the level of initiation of transcription and by inhibiting N-myc promoter activity. Comparison across neuroblastoma cell lines of the amount of residual cellular N-myc protein with the extent of apoptosis measured as pan-caspase activity after 48 h of iron chelation reveals no correlation, suggesting that the decrease in N-myc expression is unlikely to mediate apoptosis. In conclusion, chelation of cellular iron by DFO may alter the expression of multiple genes affecting the malignant phenotype by multiple pathways. Given the clinical importance of N-myc overexpression in neuroblastoma malignancy, decreasing N-myc expression by DFO might be useful as an adjunct to current


Rotation of principal axes and birefringence in III-V lasers owing to bonding strain.
Measurements of the degree of polarization (DOP) of photoluminescence from the facets of bonded III-V semiconductor diode laser chips show shear strain. The effect of shear strain on the refractive index is investigated. Finite element method (FEM) simulations are matched to the facet map of the DOP for a bonded GaAs chip and are used to extract estimates of the strain induced by die attach. Given estimates of the strains from the FEM simulations, changes in the refractive indices and rotations of the principal axes are calculated for the chip. This work has value in understanding operational changes owing to bonding-induced strain.


Novel Nicotine Delivery Systems.
Electronic nicotine delivery systems (ENDS) are devices that contain a power source, a heating element, and a tank or cartridge containing an "e-liquid," which is a mixture of nicotine and flavoring in a glycerol-propylene glycol vehicle. Their increasing popularity among adolescents might be attributed to aggressive marketing in physical venues, social media outlets, as well as irreversible changes caused by nicotine in the developing brains of youth and young adults, predisposing them to addictive behaviors. Adolescent ENDS users were 4 times more likely to initiate cigarette smoking, and the odds of quitting smoking were lower and, in many instances, delayed for those using ENDS. ENDS also renormalize cigarette-like behaviors, such as inhaling/exhaling smoke. The oral cavity is the initial point of contact of ENDS and the first affected system in humans. Oral health depends on an intricate balance in the interactions between oral bacteria and the human immune system, and dysbiosis of oral microbial communities underlies the etiology of periodontitis, caries, and oral cancer. Emerging evidence from subjects with periodontitis as well as periodontally healthy subjects demonstrates that e-cigarette use is associated with a compositional and functional shift in the oral microbiome, with an increase in opportunistic pathogens and virulence traits.


Molecular Determinants Elucidate the Selectivity in Abscisic Acid Receptor and HAB1 Protein Interactions.
The abscisic acid (ABA), as a pivotal plant hormone, plays a key role in controlling the life cycle and adapting to the environmental stresses. The receptors of ABA are the Pyrabactin resistance/Pyrabactin resistance-like/regulatory component of ABA receptors (PYR/PYL/RCAR, PYLs for simplicity), which regulate the protein phosphatase 2Cs (PP2Cs) in the signal pathway. As an important ABA-mimicking ligand, Pyrabactin shows the activation function to parts of members of PYLs, such as PYR1 and PYL1. Due to the antagonism of Pyrabactin to PYL2, it was used as a probe to discover a part of ABA receptors. Since then, many researchers have been trying to find out the determinants of the selective regulation of PYLs and PP2Cs interaction. However, the roles of residues on the selective regulation of PYR1/PYL2 and PP2Cs interaction induced by Pyrabactin are still ambiguous. This research investigated the selective activation mechanism of Pyrabactin through the sequence alignment, molecular docking, molecular dynamics simulation, and binding free energy calculation. Furthermore, the electrostatic and hydrophobic interaction differences induced by Pyrabactin and agonists were compared. The results indicate that Leu137/Val114, Ser85/Ser89, and Gly86/Gly90 from the pocket and gate of PYR1/PYL2 are the vital residues for the selective activation of Pyrabactin. Meanwhile, the electrostatic interaction between PP2Cs and PYLs complexed with agonists was improved. This mechanism provides strong support for the design of selective agonists and antagonists.


[Analysis of the dependence of the parameters of staphylococcal resistance to oxacillin established in various test systems].
Resistance parameters of 17 clinical strains of Staph, aureus to oxacillin were studied with the methods of agar diffusion and serial dilutions in liquid and solid media. Statistically reliable correlation between the parameter values of resistance and growth inhibition zone diameters on diffusion into agar of 100 gamma of oxacillin was found. The latter method provided classification of the strains into groups with high, intermediate and low resistance levels. However, calculation of the resistance parameters according to the corresponding correlation equation was not enough correct for providing distinction in the resistance levels within the groups.