Inverse association between social support and household food insecurity in a metropolitan area of Rio de Janeiro, Brazil.
To verify the association between perceived social support and household food insecurity (HFI). A cross-sectional survey. A population-based study with a representative sample of households from a metropolitan area of Rio de Janeiro, Brazil, conducted in 2010. HFI was estimated with the Brazilian Food Insecurity Scale (EBIA). Social support was assessed using the adapted and validated Brazilian version of the Medical Outcomes Study Social Support Survey. Multinomial logistic regression was used to evaluate the association between social support and HFI, adjusting for potential confounders. Adults (n 1022) aged 19-60 years old (27% men, 73% women) who were responsible for feeding the household. Individuals with high scores of social support were less likely to experience moderate HFI (OR=0·96; 95% CI 0·94, 0·99) and severe HFI (OR=0·96; 95% CI 0·94, 0·98). These findings indicate that social support may contribute to reducing HFI in populations vulnerable to poverty. Strategies to increase social relationships should be encouraged in this group to enhance their perceived social support.


Enhancement of murine immune responses to orally administered haptenated Streptococcus mutans.
The induction of immune responses to orally administered trinitrophenyl (TNP)-haptenated Streptococcus mutans and its enhancement with muramyldipeptide (MDP), peptidoglycan (PG), and concanavalin A (Con A) were investigated in lipopolysaccharide (LPS)-non-responsive C3H/HeJ mice and the syngeneic, LPS-responsive C3H/HeN strain. Both mouse strains manifested similar immune responses, primarily of the IgM isotype, after a single gastric intubation (GI) with TNP-S. mutans. However, when groups of animals were first carrier-primed by GI with S. mutans for 2 consecutive days, followed by a single GI with TNP-S. mutans 1 week later, C3H/HeJ mice gave a significantly higher (P less than or equal to 0.01) splenic IgA anti-TNP plaque-forming cell (PFC) response than identically treated C3H/HeN mice. Furthermore, saliva, urine and serum from these C3H/HeJ mice possessed high levels of IgA anti-TNP antibodies as determined by the enzyme-linked immunosorbent assay, whereas C3H/HeN mice exhibited low antibody levels. Oral administration of Con A (either 250 micrograms or 500 micrograms/mouse) or purified PG (1 mg/mouse) at the time of TNP-S. mutans immunization resulted in significantly (P less than or equal to 0.01) enhanced splenic IgA anti-TNP PFC responses, especially in C3H/HeJ mice. On the other hand, MDP promoted IgA anti-TNP PFC responses in LPS-responsive C3H/HeN mice but did not augment responses in C3H/HeJ animals. A similar immune response pattern was seen when antibody levels were measured in serum, saliva, and urine of both mouse strains. These results demonstrate that haptenated S. mutans is a good antigen for the induction of high IgA responses in orally immunized C3H/HeJ mice and that this high response can be enhanced with the adjuvants Con A and PG. However, MDP is ineffective in C3H/HeJ mice but enhances IgA responses in normal LPS-responsive C3H/HeN animals.


Individual differences in cocaine seeking during voluntary abstinence predicts cocaine relapse and the circuitry mediating relapse.
There are no FDA-approved treatments to facilitate recovery from cocaine use disorder. Contingency management offers non-drug reinforcers to encourage abstinence and is effective at reducing drug seeking during treatment, but once discontinued, relapse rates increase. We sought to establish a choice-based rodent model of voluntary abstinence (VA) from cocaine to test the ability of ceftriaxone, an antibiotic consistently shown to prevent relapse to cocaine seeking in rodents, to attenuate relapse after discontinuation of VA, and to investigate relapse-induced neuronal activation via c-Fos expression. Male Sprague-Dawley rats self-administered sucrose pellets for 5 days and intravenous cocaine for 12 days. Rats then underwent 14 days of voluntary or forced abstinence. VA sessions entailed the opportunity to choose between sucrose and cocaine delivery in discrete trials (20 trials/day). Ceftriaxone (or vehicle) was administered during the last 7 days of abstinence. During a relapse test, only the cocaine-paired lever was available and presses on the lever delivered cocaine-paired cues. There were more presses on the sucrose lever during VA, but cocaine intake did not decline to zero. Ceftriaxone had no effect on cocaine intake during VA. Neither ceftriaxone nor VA reduced cocaine seeking during the relapse test, and cocaine intake during VA positively correlated with cocaine seeking during the test in vehicle-treated animals. Relapse-induced c-Fos expression was found to be greater in the ventral orbitofrontal cortex following VA. Sucrose availability leads to a decrease in, but not cessation of, cocaine seeking and a differential engagement of the circuitry underlying relapse.


Terminal end of retro-aortic root branch: An unrecognized origin for "proximal left anterior fascicle" premature ventricular complexes with narrow QRS duration.
Premature ventricular complexes (PVCs) with narrow QRS duration, inferior frontal plane QRS axis, and right bundle branch block (RBBB) pattern generally originate from the proximal segment of the left anterior fascicle (LAF). The purpose of this study was to investigate the exact origin of this category of PVCs. Twenty-two patients with assumed proximal LAF-PVCs were enrolled in the study. Detailed mapping of fascicular potentials (FPs) was performed during sinus rhythm (SR) and PVCs. During SR, a cluster of FPs could be found at the most superior portion of the left ventricle (LV). These FPs represented the terminal end of a discrete branch of the left fascicular system, which we named the "retro-aortic root branch" (RARB). The shortest distance between the proximal LAF and the terminal end of the RARB was 13.5 ± 4.2 mm. The earliest activation site (EAS) of PVCs in all patients were confirmed at the terminal end of the RARB, where the FP-V interval was 35.1 ± 4.3 ms during PVCs. The shortest distance from the right coronary cusp (RCC) to the EAS was 5.3 ± 3.5 mm. PVCs could be eliminated by ablation from the RCC in 45.5% (10/22) cases, in the remaining cases, ablation at the EAS in the LV endocardium successfully abolished PVCs. The terminal end of the retro-aortic root branch was the actual origin site for PVCs with inferior frontal plane axis, RBBB pattern and narrow QRS duration. Ablation in the RCC or at the EAS in the LV could both eliminate PVCs safely with high efficacy.


Comparative miRNAs analysis of Two contrasting broccoli inbred lines with divergent head-forming capacity under temperature stress.
MicroRNAs (miRNAs) play a vital role in growth, development, and stress response at the post-transcriptional level. Broccoli (Brassica oleracea L. var italic) is an important vegetable crop, and the yield and quality of broccoli are decreased by heat stress. The broccoli inbred lines that are capable of producing head at high temperature in summer are unique varieties in Taiwan. However, knowledge of miRNAomes during the broccoli head formation under heat stress is limited. In this study, molecular characterization of two nearly isogenic lines with contrasting head-forming capacity was investigated. Head-forming capacity was better for heat-tolerant (HT) than heat-sensitive (HS) broccoli under heat stress. By deep sequencing and computational analysis, 20 known miRNAs showed significant differential expression between HT and HS genotypes. According to the criteria for annotation of new miRNAs, 24 novel miRNA sequences with differential expression between the two genotypes were identified. To gain insight into functional significance, 213 unique potential targets of these 44 differentially expressed miRNAs were predicted. These targets were implicated in shoot apical development, phase change, response to temperature stimulus, hormone and energy metabolism. The head-forming capacity of the unique HT line was related to autonomous regulation of Bo-FT genes and less expression level of heat shock protein genes as compared to HS. For the genotypic comparison, a set of miRNAs and their targets had consistent expression patterns in various HT genotypes. This large-scale characterization of broccoli miRNAs and their potential targets is to unravel the regulatory roles of miRNAs underlying heat-tolerant head-forming capacity.


BRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cells.
Loss of 53BP1 rescues BRCA1 deficiency and is associated with BRCA1-deficient and triple-negative breast cancers (TNBC) and with resistance to genotoxic drugs. The mechanisms responsible for decreased 53BP1 transcript and protein levels in tumors remain unknown. Here, we demonstrate that BRCA1 loss activates cathepsin L (CTSL)-mediated degradation of 53BP1. Activation of this pathway rescued homologous recombination repair and allowed BRCA1-deficient cells to bypass growth arrest. Importantly, depletion or inhibition of CTSL with vitamin D or specific inhibitors stabilized 53BP1 and increased genomic instability in response to radiation and poly(adenosine diphosphate-ribose) polymerase inhibitors, compromising proliferation. Analysis of human breast tumors identified nuclear CTSL as a positive biomarker for TNBC, which correlated inversely with 53BP1. Importantly, nuclear levels of CTSL, vitamin D receptor, and 53BP1 emerged as a novel triple biomarker signature for stratification of patients with BRCA1-mutated tumors and TNBC, with potential predictive value for drug response. We identify here a novel pathway with prospective relevance for diagnosis and customization of breast cancer therapy.


Elucidation of DnaE as the Antibacterial Target of the Natural Product, Nargenicin.
Resistance to existing classes of antibiotics drives the need for discovery of novel compounds with unique mechanisms of action. Nargenicin A1, a natural product with limited antibacterial spectrum, was rediscovered in a whole-cell antisense assay. Macromolecular labeling in both Staphylococcus aureus and an Escherichia coli tolC efflux mutant revealed selective inhibition of DNA replication not due to gyrase or topoisomerase IV inhibition. S. aureus nargenicin-resistant mutants were selected at a frequency of ∼1 × 10(-9), and whole-genome resequencing found a single base-pair change in the dnaE gene, a homolog of the E. coli holoenzyme α subunit. A DnaE single-enzyme assay was exquisitely sensitive to inhibition by nargenicin, and other in vitro characterization studies corroborated DnaE as the target. Medicinal chemistry efforts may expand the spectrum of this novel mechanism antibiotic.


Gallic acid degradation in aqueous solutions by UV/H2O2 treatment, Fenton's reagent and the photo-Fenton system.
Gallic acid (3,4,5-trihydroxybenzoic acid) is a major pollutant present in the wastewater generated in the boiling cork process, as well as in other wastewaters from food manufacturing industries. Its decay in aqueous solutions has been studied by the action of several oxidation systems: monochromatic UV radiation alone and combined with hydrogen peroxide, Fenton's reagent and the combination Fenton's reagent with UV radiation (photo-Fenton system). The influence of the pH is discussed and the quantum yields are determined in the UV radiation system. Also, the influence of operating variables (initial concentrations of H2O2 and Fe(II), and pH) is established in the Fenton's reaction. The apparent pseudo-first-order rate constants are evaluated in all the experiments conducted in order to compare the efficiency of each one of the processes. Increases in the degradation levels of gallic acid are obtained in the combined processes in relation to the single UV radiation system, due to reactions of the very reactive OH*. These improvements are determined in every process by calculating the partial contribution to the overall decomposition rate of the radical pathways. For the oxidant concentrations applied, the most effective process in removing gallic acid was found to be the photo-Fenton system. The rate constant for the reaction of gallic acid with OH was also determined by means of a competition kinetics model, being its value 11.0+/-0.1 x 10(9)l mol(-1)s(-1).


Antipsychotic polypharmacy at the University Psychiatric Hospital in Serbia.
The aim of the study was to analyse the prevalence of polypharmacy with antipsychotic drugs and analyse types of coprescribing episodes at the University Psychiatric Hospital in Serbia. A sample of 120 patients (198 hospitalisations) was analysed. The prevalence of polypharmacy was calculated as the proportion of patients receiving two or more antipsychotic drugs concomitantly for at least 28 days. Total daily antipsychotic drug load was calculated as the number of defined daily doses (DDDs) of drugs per patient per day. It was compared between patients receiving monotherapy and patients receiving polypharmacy. Statistics was performed using standard statistical methods. Monotherapy was prescribed during 32.3% hospitalisations (n = 64), while polypharmacy was noted in 67.7% (n = 134). Polypharmacy with two drugs was observed during 126 (63.6%) hospitalisations and three antipsychotics were prescribed concomitantly during 8 (4.1%) hospitalisations. Patients' characteristics were not significantly different between patients who received only monotherapy and patients receiving polypharmacy. Patients on monotherapy had significantly more prior hospitalisations than patients from the other group (t = 3.94, df = 119, p < 0.001). The prevalence of polypharmacy patient episodes (67.7%) is approximately 100% higher than the prevalence observed in developed European countries. The explanation of such prescribing habit of Serbian psychiatrists requires further investigation. The only distinguishing factor between patients receiving monotherapy and patients receiving polypharmacy is the number of prior hospitalisations.


Preparation of monoclonal antibodies reactive to the endogenous small molecule, anandamide.
The development of an easy and inexpensive immunoassay to measure the limited quantities of endogenous cannabinoids found in the body would be beneficial for both cannabinoid researchers and clinicians. This report describes the hapten design and carrier molecule strategy that we used to generate a panel of monoclonal antibodies (mAB) to the endogenous cannabinoid anandamide (N-arachidonylethanolamide, AEA). We designed and successfully prepared a hapten, N-arachidonyl-7-amino-6-hydroxy-heptanoic acid (AHA), which retained the basic characteristic features of anandamide--the carboxamide, the hydroxyl and the lipophilic arachidonyl moiety with its skipped double bond system, while still allowing attachment to protein. In addition, a secondary alcohol structure was added to reduce the potential for biological hydrolysis of the hapten. Because of the diverse responses obtained after coupling this hapten to four different carriers, we determined that the type of carrier molecule used was particularly important for generating anti-anandamide antibodies. Described in this report are the characteristics of a panel of 11 mAB, generated from four separate fusions, with a range of relative affinities and cross reactivities. Excellent selectivity for anandamide vs. two other endogenous cannabinoids and arachidonic acid was achieved this strategy (cross-reactivities <5%). In addition, at least one mAB maintained specificity for anandamide compared to two very closely related fatty acid amide molecules. However, the IC50 values in a standard enzyme-linked immunosorbent assay (ELISA) format (ca. 2-3 microM) indicate that improvement in antibody affinities or assay format will be required for an immunoassay to measure endogenous levels. Such work is underway.


New Fractional Modelling, Analysis and Control of the Three Coupled Multiscale Non-Linear Buffering System.
This study aims to investigate the complicated dynamical H C O 3 - / C O 2 buffering system using fractional operators which is not been investigated yet. We consider a new fractional mathematical model in the frame of fractional-order differential equations. In the proposed fractional-order model, we apply the Caputo-Fabrizio fractional operator with an exponential kernel. Then to solve the derived system of fractional equations, we suggest a quadratic numerical technique and prove its stability and convergence. Also, accurate control for the proposed system is considered. Behaviors of the approximate solutions for the considered model are provided by choosing different values of fractional orders along with integer order. Each figure manifests and compares the numerical solutions under selected orders. Figures, show how the results can be affected by changing the fractional orders.


Comparison of occurrence of antibodies to human cytomegalovirus as demonstrated by immunofluorescence and indirect hemagglutination techniques.
Indirect immunofluorescence and hemagglutination study of reactivity to human cytomegalovirus immediate early, early, and late antigens revealed that antibody responses to these antigens varies greatly and that hemagglutination is positive when sera contain only antibody to one or both early antigens.


Vehicle exhausts contribute high near-UV absorption through carbonaceous aerosol during winter in a fast-growing city of Sichuan Basin, China.
Carbonaceous aerosols pose significant climatic impact, however, their sources and respective contribution to light absorption vary and remain poorly understood. In this work, filter-based PM2.5 samples were collected in winter of 2021 at three urban sites in Yibin, a fast-growing city in the south of Sichuan Basin, China. The composition characteristics of PM2.5, light absorption and source of carbonaceous aerosol were analyzed. The city-wide average concentration of PM2.5 was 87.4 ± 31.0 μg/m3 in winter. Carbonaceous aerosol was the most abundant species, accounting for 42.5% of the total PM2.5. Source apportionment results showed that vehicular emission was the main source of PM2.5 during winter, contributing 34.6% to PM2.5. The light absorption of black carbon (BC) and brown carbon (BrC) were derived from a simplified two-component model. We apportioned the light absorption of carbonaceous aerosols to BC and BrC using the Least Squares Linear Regression with optimal angstrom absorption exponent of BC (AAEBC). The average absorption of BC and BrC at 405 nm were 51.6 ± 21.5 Mm-1 and 17.7 ± 8.0 Mm-1, respectively, with mean AAEBC = 0.82 ± 0.02. The contribution of BrC to the absorption of carbonaceous reached 26.1% at 405 nm. Based on the PM2.5 source apportionment and the mass absorption cross-section (MAC) value of BrC at 405 nm, vehicle emission was found to be the dominant source of BrC in winter, contributing up to 56.4%. Therefore, vehicle emissions mitigation should be the primary and an effective way to improve atmospheric visibility in this fast-developing city.


Hyperthermic therapy of deep seated tumors: comparison of the heating efficiencies of an annular array applicator and a capacitively coupled radiofrequency system.
Among 82 cases of deep seated tumors treated by hyperthermia with an annular array applicator (AA) and/or a capacitively coupled 8 mHz system (CCS) combined with radiation therapy, 13 cases were treated by both devices. The efficiencies of tumor heating were compared in terms of the time required to attain 42 degrees C, the duration of heating time and the thermal dose as determined by a biological iso-effect formula for equivalent minutes at 42.5 degrees C. Temperature profiles and percent of temperature levels greater than 42 degrees C were better in the cases treated by the AA, but higher thermal doses were obtained with the CCS because longer treatment times were tolerated with the CCS than with the AA. Methods are necessary to prevent excess elevation of body temperature in the case of the AA, and to reduce superficial pain where the applicators contact the skin in the case of the CCS.


Cannabis Motives and Quitting Tobacco: Smoking Expectancies and Severity among Treatment-seeking Cigarette Smokers.
The present research examined the impact of cannabis motives on tobacco outcomes. The sample included 403 daily smokers (214 males, mean age 35.24 years). A bifactor model of cannabis motives was examined to determine whether this approach might best elucidate relations between cannabis motives and smoking. Coping motives were associated with reduced barriers for smoking, fewer negative smoking expectancies, and decreased positive reinforcement with respect to smoking. Conformity motives were associated with fewer internal smoking barriers. Expansion motives were associated with more positive reinforcement related to smoking. Enhancement motives were associated with reductions in smoking for appetite/weight control consequences. The general motives variable, comprised of each of the five motives subscales, was associated with more barriers related to tobacco addiction, more external barriers, greater positive reinforcement consequences, and more negative expectancies. Coping motives were negatively associated with quit status, and were positively associated with quit status. Cannabis motives subscales were not uniformly predictive of quit success. Individuals who used cannabis for conformity reasons were more likely to successfully quit smoking, however, individuals who used cannabis for coping reasons were less likely to quit smoking. Thus, those who use cannabis for conformity reasons are less likely to turn to cannabis during times of stress or to relieve tension or anxiety, a view supported by existing literature. This suggests that individuals who use cannabis for coping reasons may represent a population vulnerable to cannabis misuse and problems. Additional work is needed to better understand underlying mechanisms.


Retention of monodisperse or polydisperse aluminosilicate particles inhaled by dogs, rats, and mice.
This study compared long-term retention of 134Cs-labeled fused aluminosilicate particles inhaled by three animal species. Dogs, rats, and mice were briefly exposed to 0.7-, 1.5-, or 2.8-micron activity median aerodynamic diameter (AMAD) monodisperse particles or a polydisperse aerosol with 1.5 to 2.0 micron AMAD and geometric standard deviation of 1.5 to 2.0. Tissues and excreta were collected for up to 850 days after exposure to determine retention and clearance patterns of the inhaled particles. Simulation models were developed for each animal species and aerosol. Solubilization was the dominant factor in long-term lung clearance for most of the particles inhaled by dogs; mechanical clearance was dominant in rats and mice. After accounting for solubility, physical clearance from the lung to the gastrointestinal tract and to lung-associated lymph nodes (LALNs) was independent of particle size within the size range investigated. Rats and mice demonstrated a rapid clearance from the pulmonary region, with most of the mechanically cleared particles going to the gastrointestinal tract; significant translocation to the LALNs occurred for only a few days. The dogs cleared deposited particles at a slower rate, with most of the long-term clearance going to LALNs. A small portion of the initial deposit was retained in the upper respiratory tract of all three species. Results from the data for dogs were used to make long-term predictions for chronic inhalation of particles by humans.


An engineered toluene dioxygenase for a single step biocatalytical production of (-)-(1S,2R)-cis-1,2-dihydro-1,2-naphthalenediol.
cis-1,2-Dihydro-1,2-naphthalenediol (DHND) is a valuable molecule employed for the pharmaceutical synthesis of bioactive compounds, such as bicyclic conduritol analogues. Enantiopure (+)-(1R,2S)-DHND (>98 % ee) is easily biosynthesized through the dearomatizing dihydroxylation of naphthalene, catalyzed by toluene dioxygenase (TDO) from Pseudomonas putida F1. However, the opposite enantiomer (-)-(1S,2R)-DHND could not be directly accessed, neither by chemical synthesis nor via biocatalytic approaches. Herein, we report a one-step biosynthesis of the opposite enantiomer (-)-(1S,2R)-DHND in a recombinant TDO E. coli BW25113 platform. We based on a semi-rational approach to generate a set of TDO variants, targeting exclusively the hotspot position F366, in order to enable an enantiomeric switch in the generated product. Eight out of nine single point variants were active and showed not only an alteration in enantioselectivity, but also generated an enantiomeric excess of the pursued product. Variant TDOF366V outperformed above the rest of the set, enabling the synthesis of (-)-(1S,2R)-DHND not only with an excellent enantiomeric excess of 90 %, but also with an advantageous product formation. A comparative semi-preparative biosynthesis yielded, 287 mg of (+)-(1R,2S)-DHND (>98 % ee) and 101 mg of (-)-(1S,2R)-DHND (90 % ee), when performed in a total volume of 100 mL with TDO wild-type and TDOF366V resting cells, respectively.


Rac and Rap GTPase activation assays.
The detection of Ras superfamily GTPase activity in neutrophils is important when studying signaling events elicited by various ligands and cellular processes. Substantial progress in monitoring GTPase activation has been made in recent years by the development of high-affinity probes for small GTPases. These probes are created by fusing a high-affinity GTPase-binding domain derived from a specific downstream effector protein to glutathione-S-transferase (GST). Such domains bind preferentially to the GTP-bound form of specific Rho or Ras GTPases. Coupling these probes to beads enables extraction of the complex and subsequent quantification of active GTP-binding protein by immunoblotting. Although effector domains that discriminate efficiently between GDP- and GTP-bound states and highly specific antibodies are not yet available for many small GTPases, analysis of certain members of the Rho and Ras GTPase family are now routinely performed. Here, we describe affinity-based pull-down assays for detection of Rac/Cdc42 and Rap activity in stimulated neutrophils.


Institutional case volume and mortality after aortic and mitral valve replacement: a nationwide study in two Korean cohorts.
There are only a handful of published studies regarding the volume-outcome relationship in heart valve surgery. We evaluated the association between institutional case volume and mortality after aortic valve replacement (AVR) and mitral valve replacement (MVR). Two separate cohorts of all adults who underwent AVR or MVR, respectively, between 2009 and 2016 were analyzed using a Korean healthcare insurance database. Hospitals performing AVRs were divided into three groups according to the average annual case volume: the low- (< 20 cases/year), medium- (20-70 cases/year), and high-volume centers (> 70 cases/year). Hospitals performing MVRs were also grouped as the low- (< 15 cases/year), medium- (15-40 cases/year), or high-volume centers (> 40 cases/year). In-hospital mortality after AVR or MVR were compared among the groups. In total, 7875 AVR and 5084 MVR cases were analyzed. In-hospital mortality after AVR was 8.3% (192/2318), 4.0% (84/2102), and 2.6% (90/3455) in the low-, medium-, and high-volume centers, respectively. The adjusted risk was higher in the low- (OR 2.31, 95% CI 1.73-3.09) and medium-volume centers (OR 1.53, 95% CI 1.09-2.15) compared to the high-volume centers. In-hospital mortality after MVR was 9.3% (155/1663), 6.3% (94/1501), and 2.9% (56/1920) in the low-, medium-, and high-volume centers, respectively. Compared to the high-volume centers, the medium- (OR 1.97, 95% CI 1.35-2.88) and low-volume centers (OR 2.29, 95% CI 1.60-3.27) showed higher adjusted risk of in-hospital mortality. Lower case volume is associated with increased in-hospital mortality after AVR and MVR. The results warrant a comprehensive discussion regarding regionalization/centralization of cardiac valve replacements to optimize patient outcomes.


Evolution of pattern of injury and quantitative MRI on days 1 and 3 in term newborns with hypoxic-ischemic encephalopathy.
Brain injury in term neonatal hypoxic-ischemic encephalopathy (HIE) emerges on magnetic resonance imaging (MRI) by day 3. This study aimed to address the relationship of MRI, diffusion tensor imaging (DTI), and MR spectroscopic imaging (MRSI) findings on days 1 and 3 in a prospective cohort of term newborns with HIE. A total of 24 term newborns with HIE were prospectively studied with MRI on days 1 and 3; 19 were imaged with DTI and MRSI on days 1 and 3. MRI was assessed using validated scores. The relationship between MRI, DTI, and MRSI values on days 1 and 3 was determined using linear regression for repeated measures. Conventional MRI showed a complex variation of findings from day 1 to 3. In gray matter, mean diffusivity (Dav) and metabolite ratios measured on day 1 were predictive of values on day 3 (all P ≤ 0.04). In white matter, Dav, fractional anisotropy (FA), and N-acetylaspartate (NAA)/choline on days 1 and 3 were strongly related (all P ≤ 0.003). Hypothermia appeared to attenuate the severity and progression of brain injury in the six treated newborns. In term newborns with HIE, quantitative MR values on days 1 and 3 are strongly associated, providing an objective measure of injury before qualitative images.


Ceftriaxone inhibits stress-induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.
Emotional stress plays a role in the exacerbation and development of interstitial cystitis/bladder pain syndrome (IC/BPS). Given the significant overlap of brain circuits involved in stress, anxiety, and micturition, and the documented role of glutamate in their regulation, we examined the effects of an increase in glutamate transport on central amplification of stress-induced bladder hyperalgesia, a core feature of IC/BPS. Wistar-Kyoto rats were exposed to water avoidance stress (WAS, 1 hour/day x 10 days) or sham stress, with subgroups receiving daily administration of ceftriaxone (CTX), an activator of glutamate transport. Thereafter, cystometrograms were obtained during bladder infusion with visceromotor responses (VMR) recorded simultaneously. Cerebral blood flow (CBF) mapping was performed by intravenous injection of [14 C]-iodoantipyrine during passive bladder distension. Regional CBF was quantified in autoradiographs of brain slices and analyzed in three dimensional reconstructed brains with statistical parametric mapping. WAS elicited visceral hypersensitivity during bladder filling as demonstrated by a decreased pressure threshold and VMR threshold triggering the voiding phase. Brain maps revealed stress effects in regions noted to be responsive to bladder filling. CTX diminished visceral hypersensitivity and attenuated many stress-related cerebral activations within the supraspinal micturition circuit and in overlapping limbic and nociceptive regions, including the posterior midline cortex (posterior cingulate/anterior retrosplenium), somatosensory cortex, and anterior thalamus. CTX diminished bladder hyspersensitivity and attenuated regions of the brain that contribute to nociceptive and micturition circuits, show stress effects, and have been reported to demonstrated altered functionality in patients with IC/BPS. Glutamatergic pharmacologic strategies modulating stress-related bladder dysfunction may be a novel approach to the treatment of IC/BPS.


Traumatic renal arteriovenous fistula.
A case of a 29-year-old man who developed a renal arteriovenous fistula after a gunshot injury is reported. The patient presented with renovascular hypertension associated with high putput cardiac failure, both of which were reversed by surgery.


Synthesis, spectroscopic and luminescence properties of Ga-doped γ-Al2O3.
Gallium-doped aluminum oxide (Al1-xGax)2O3 with γ-Al2O3 (spinel) structure has been synthesized by the precursor method using the formate Al1-xGax(OH)(HCOO)2 as a precursor. The examination of Al1-xGax(OH)(HCOO)2 (x = 0.0, 0.1, 0.2, 0.3, 0.4) was carried out by X-ray powder diffraction, Infrared, Raman spectroscopy and differential-thermal methods. The solid solutions γ-(Al1-xGax)2O3 with х≤0.2 have been synthesized by thermolysis of precursors in helium atmosphere at 700 °C; they exhibit white-blue emission under UV excitation, whose intensity lowers with increasing dopant concentration. As an independent method, the DFT calculations confirmed thermodynamically the stability field of γ-(Al1-xGax)2O3 solid solutions and the NMR data on relative abundance of Al and Ga within the tetrahedral and octahedral sites in the metal sublattice. Furthermore, the structural and thermodynamic properties of carbon-containing impurities within these compounds were suggested theoretically as possible models of luminescence emission centers. The experimentally observed Ga-dependent quenching of luminescence was explained using the competition between C2p and Ga4p states within the band gap of γ-Al2O3.


Monitoring and evaluation for coronary artery bypass grafts.
Cardiovascular surgeons on the medical staff at Southeast Missouri Hospital, Girardeau, developed indicators, including indications, complications, and outcomes, for the monitoring and evaluation of coronary artery bypass grafts. When the number of sternal wound infections exceeded the threshold for evaluation, action was taken and the occurrence of such infections subsequently declined.


Design and development of a new micro-beam treatment planning system: effectiveness of algorithms of optimization and dose calculations and potential of micro-beam treatment.
A new treatment planning system (TPS) was designed and developed for a new treatment system, which consisted of a micro-beam-enabled linac with robotics and a real-time tracking system. We also evaluated the effectiveness of the implemented algorithms of optimization and dose calculations in the TPS for the new treatment system. In the TPS, the optimization procedure consisted of the pseudo Beam's-Eye-View method for finding the optimized beam directions and the steepest-descent method for determination of beam intensities. We used the superposition-/convolution-based (SC-based) algorithm and Monte Carlo-based (MC-based) algorithm to calculate dose distributions using CT image data sets. In the SC-based algorithm, dose density scaling was applied for the calculation of inhomogeneous corrections. The MC-based algorithm was implemented with Geant4 toolkit and a phase-based approach using a network-parallel computing. From the evaluation of the TPS, the system can optimize the direction and intensity of individual beams. The accuracy of the dose calculated by the SC-based algorithm was less than 1% on average with the calculation time of 15 s for one beam. However, the MC-based algorithm needed 72 min for one beam using the phase-based approach, even though the MC-based algorithm with the parallel computing could decrease multiple beam calculations and had 18.4 times faster calculation speed using the parallel computing. The SC-based algorithm could be practically acceptable for the dose calculation in terms of the accuracy and computation time. Additionally, we have found a dosimetric advantage of proton Bragg peak-like dose distribution in micro-beam treatment.


A single half-turnover of the glucose carrier of the human erythrocyte.
Single half-turnovers of the glucose carrier of the human erythrocyte have been measured by recruiting carriers to the outward-facing conformation by (a) pre-exposing cells to extracellular maltose, or (b) pre-warming cells to 38 degrees C, before addition of D-[14C]glucose at 0 degrees C. Based on these experiments estimates of the number of glucose carriers per red cell range from 124,000 to 190,000.


Cooperative interactions between calcium-binding sites on glycerinated muscle fibers. The influence of cross-bridge attachment.
A double isotope technique and EGTA buffers were used to measure the binding of Ca2+ to rabbit psoas muscle fibers extracted with detergent and glycerol. These experiments were designed to test the effect of rigor complex formation, determined by the degree of filament overlap, on the properties of the Ca2+-binding sites in the intact filament lattice. In the presence of 5 mM MgCl2 (no ATP), reduction of filament overlap was associated with a reduced binding of Ca2+ over the entire range of free Ca2+ concentrations (5.10(-8)-2.10(-5) M). With maximum filament overlap (sarcomere length 2.1-2.2 micrometer) the maximum bound Ca2+ was equivalent to 4 mol Ca2+/mol troponin and there was significant positive interaction between binding sites, as shown by Scatchard and Hill plots. With no filament overlap (sarcomere length 3.8-4.4 micrometer) the maximum bound Ca2+ was equivalent to 3 mumole Ca2+/mol troponin and graphical analysis indicated a single class of non-interacting sites. The data provide evidence that when cross-bridge attachments between actin and myosin filaments are formed not only does an additional Ca2+ binding site appear, but cooperative properties are imposed upon the binding sites.


Fruit, vegetable consumption and blood pressure in healthy adolescents: A longitudinal analysis from the LabMed study.
The associations between fruit and vegetable consumption and high blood pressure among adults are well studied. Nonetheless, data on the influence of a low consumption of fruit and vegetables on cardiovascular disease risk, particularly blood pressure, among healthy adolescents are scarce. Therefore, we aim to analyse the associations between fruit and/or vegetable intake and blood pressure over a two-year period in healthy adolescents. As part of a cohort, 606 adolescents from the LabMed Physical Activity study were evaluated in 2011 (baseline) and 2013 (follow-up). Blood pressure was measured according to standardized procedures and fruit and vegetable consumption was assessed with a food frequency questionnaire. Anthropometric variables, socioeconomic status, pubertal stage and lifestyle determinants were gathered and used as confounders. Prospective associations between fruit and/or vegetable intake and blood pressure were examined using generalized linear models. Girls who consumed more fruit at baseline had a significant decrease in diastolic blood pressure at follow-up [unstandardized beta: -0.005 mmHg (95%CI: -0.01; -0.0002) (p = 0.038)]. In apparently healthy adolescents, fruit intake may already start to have an effect in blood pressure. Girls who consumed more fruit exhibited lower levels of diastolic blood pressure.


Enhancing oxygen reduction reaction in air-cathode microbial fuel cells treating wastewater with cobalt and nitrogen co-doped ordered mesoporous carbon as cathode catalysts.
The sluggish oxygen reduction reaction (ORR) on the cathode severely limits the energy conversion efficiency of microbial fuel cells (MFCs). In this study, cobalt and nitrogen co-doped ordered mesoporous carbon (Cox-N-OMC) was prepared by heat-treating a mixture of cobalt nitrate, melamine and ordered mesoporous carbon (OMC). The addition of cobalt nitrate remarkably improved the ORR reactivity, compared to the nitrogen-doped OMC catalyst. By optimizing the dosage of cobalt nitrate (x = 0.6, 0.8 and 1.0 g), the Co0.8-N-OMC catalyst displayed excellent ORR catalytic performances in neutral media with the onset potential of 0.79 V (vs. RHE), half-wave potential of 0.59 V and limiting current density of 5.43 mA/cm2, which was comparable to the commercial Pt/C catalyst (0.86 V, 0.60 V and 4.76 mA/cm2). The high activity of Co0.8-N-OMC catalyst was attributed to the high active surface area, higher total nitrogen amount, and higher relative distribution of graphitic nitrogen and pyrrolic nitrogen species. Furthermore, single chamber microbial fuel cell (SCMFC) with Co0.8-N-OMC cathode exhibited the highest power density of 389 ± 24 mW/m2, chemical oxygen demand (COD) removal of 81.1 ± 2.2% and coulombic efficiency (CE) of 17.2 ± 2.5%. On the other hand, in the Co1.0-N-OMC catalyst, increasing the cobalt dosage from 0.8 to 1.0 g resulted in more oxidized-N species, and the reduced power generation in SCMFC (360 ± 8 mW/m2). The power generated by these catalysts and results of electrochemical evaluation were strongly correlated with the total nitrogen contents on the catalyst surface. This study demonstrated the feasibility of optimizing the dosage of metal to enhance wastewater treatment capacity.


Inferoposterior ventricular septal rupture: repair with maintenance of ventricular geometry.
We present a method of repairing inferobasal ventricular septal rupture after myocardial infarction, preserving the ventricular cavity sizes. This may be useful when extensive infarction compromises ventricular geometry with other repair techniques.


Plasmonic silver/silver oxide nanoparticles anchored bismuth vanadate as a novel visible-light ternary photocatalyst for degrading pharmaceutical micropollutants.
The degradation of pharmaceutical micropollutants is an intensifying environmental problem and synthesis of efficient photocatalysts for this purpose is one of the foremost challenges worldwide. Therefore, this study was conducted to develop novel plasmonic Ag/Ag2O/BiVO4 nanocomposite photocatalysts by simple precipitation and thermal decomposition methods, which could exhibit higher photocatalytic activity for mineralized pharmaceutical micropollutants. Among the different treatments, the best performance was observed for the Ag/Ag2O/BiVO4 nanocomposites (5 wt.%; 10 min's visible light irradiation) which exhibited 6.57 times higher photodegradation rate than the pure BiVO4. Further, the effects of different influencing factors on the photodegradation system of tetracycline hydrochloride (TC-HCl) were investigated and the feasibility for its practical application was explored through the specific light sources, water source and cycle experiments. The mechanistic study demonstrated that the photogenerated holes (h+), superoxide radicals (•O2-) and hydroxyl radicals (•OH) participated in TC-HCl removal process, which is different from the pure BiVO4 reaction system. Hence, the present work can provide a new approach for the formation of novel plasmonic photocatalysts with high photoactivity and can act as effective practical application for environmental remediation.


Comparison of chromatographic band profiles obtained under microwave irradiated and non-irradiated reversed-phase liquid chromatography column.
The possible influence of the application of microwave energy to a reversed-phase liquid chromatography column on the mass transfer kinetics and the thermodynamics of equilibrium between mobile and stationary phases was examined. Chromatograms of propylbenzene and phenol were recorded under the same experimental conditions, on the same column, successively irradiated and not. The effect of microwave irradiation on the mass transfer kinetics was determined by measuring the second moment of small pulses of propylbenzene in a 70:30 (v/v) solution of methanol in water and microwave outputs of 15 and 30 W. The effect of microwave irradiation on the equilibrium thermodynamics was determined by measuring the elution time of breakthrough curves of phenol at high concentrations in a 20:80 (v/v) solution of methanol and water and microwave outputs of 15, 50, and 150 W. A qualitative comparison of the profiles of the propylbenzene peaks obtained with and without irradiation suggests that this irradiation affects significantly the peak shapes. However, a qualitative comparison of the profiles of the breakthrough curves of phenol obtained with and without irradiation suggests that this irradiation has no significant effect on their shapes. The peak sharpening observed may be due to an increase in the diffusivity, resulting from the dielectric polarization under microwave irradiation. This effect is directly related to an increase of the rate of mass transfers in the column. In contrast, the similarity of the overloaded band profiles at high concentrations suggests that the equilibrium thermodynamics is unaffected by microwave irradiation. This may be explained by the transparence of the stationary phase to microwaves at 2.45 GHz. The column temperature was measured at the column outlet under irradiation powers of 15, 30, 50, and 150 W. It increases with increasing power, the corresponding effluent temperatures being 25+/-1, 30+/-1, 35+/-1, and 45+/-1 degrees C, respectively.


Naltrexone in treatment of self injurious behavior: a clinical study.
It has been suggested that the parenteral opiate antagonist, naloxone, might ameliorate self-injurious behavior. However, clinical studies have had conflicting results. We have evaluated whether a potent oral opiate antagonist, naltrexone, is effective in the treatment of this condition. The study was conducted on two young, profoundly mentally retarded adults, who exhibited intractable self-injurious behavior. A double-blind, placebo-controlled, within-subject-withdrawal design was utilized. One subject was studied for 12 weeks and the other one for 18 weeks. No measurable effects on the self-injurious behavior were observed.


Development of a PCR amplification assay as a screening test using bulk milk samples for identifying dairy herds infected with bovine viral diarrhea virus.
The approach of cDNA synthesis followed by polymerase chain reaction (PCR) amplification was used to develop a rapid screening test for the detection of bovine viral diarrhea virus (BVDV) in bulk tank milk samples. The initial development of this detection method was done using lactating Holstein cows; 1 acutely infected with BVDV following experimental inoculation and 2 persistently infected (PI) with BVDV. Viral RNA was extracted from somatic cells purified from whole milk using a guanidinium isothiocyanate and phenol/chloroform extraction method. Oligonucleotide primers were selected from the 5'untranslated region (5'UTR) and p80 region of BVDV genome. In the acutely infected cow, BVDV RNA was identified from days 6 to 10 postinoculation. Viral RNA extracted from somatic cells of milk from PI cows was detected by PCR using both 5'UTR and p80 primer sets. The sensitivity of PCR detection was determined by preparing dilutions of whole milk obtained from the BVDV persistently infected animals with milk from a BVDV-negative cow followed by purification of somatic cells and RNA extraction. BVDV was detected in milk serially diluted to 1:640 using PCR amplification. In addition, PCR amplification was 14.6 times more sensitive than virus isolation in detecting BVDV RNA in purified milk somatic cells. PCR detected BVDV RNA from a minimum of 580 somatic cells while the detection limit of virus isolation was 8500 cells. The sensitivity and specificity of BVDV amplification were confirmed by Southern hybridization analysis. BVDV RNA was detected using PCR in 33 out of 136 bulk milk samples collected from 124 individual herds using the 5'UTR primer set. These results indicate that PCR analysis of bulk tank milk samples may provide a rapid and sensitive method of screening herds for the presence of BVDV infections.


A Pilot Randomized Trial Comparing the Effects of 80 versus 160 mg of Aspirin on Midtrimester Uterine Artery Pulsatility Index in Women with a History of Preeclampsia.
To compare the effects of 80 mg and 160 mg of aspirin, initiated in the first trimester of pregnancy, on mid-trimester uterine artery pulsatility index (UtA-PI) in women with a history of preeclampsia. We performed a pilot double-blind randomized controlled trial. Pregnant women with a history of preeclampsia were recruited between 100/7 and 136/7 weeks gestation and randomly assigned to take either 80 or 160 mg of aspirin daily at bedtime from randomization to 356/7 weeks gestation. The primary outcome was mean UtA-PI at 22-24 weeks. Secondary outcomes included the rate of fetal growth restriction and preeclampsia, stratified as term (≥37 weeks), preterm (<37 weeks), and early-onset (<34 weeks) preeclampsia. A total of 107 participants were randomized, including 41 (38%) with a history of preterm preeclampsia and 16 (15%) with a history of early-onset preeclampsia. We observed no significant difference in mean UtA-PI at 22-24 weeks between the 2 groups (0.97; 95% CI 0.88-1.05 vs. 0.97; 95% CI 0.88-1.07, P = 0.9). The rates of fetal growth restriction (8% vs. 2%; P = 0.20); preeclampsia (12% vs. 15%; P = 0.78), preterm preeclampsia (4% vs. 2%; P = 0.56), and early-onset preeclampsia (0% vs. 2%; P = 0.52) were similar in both groups. No serious adverse events associated with the study treatment were reported. We observed no significant difference in UtA-PI between the two doses of aspirin, but we observed low rates of fetal growth restriction and preterm and early-onset preeclampsia (all less than 5%). The benefits of aspirin for the prevention of preterm preeclampsia is probably not related to the improvement of deep placentation alone.


HIV proviral genetic diversity, compartmentalization and inferred dynamics in lung and blood during long-term suppressive antiretroviral therapy.
The lung is an understudied site of HIV persistence. We isolated 898 subgenomic proviral sequences (nef) by single-genome approaches from blood and lung from nine individuals on long-term suppressive antiretroviral therapy (ART), and characterized genetic diversity and compartmentalization using formal tests. Consistent with clonal expansion as a driver of HIV persistence, identical sequences comprised between 8% to 86% of within-host datasets, though their location (blood vs. lung) followed no consistent pattern. The majority (77%) of participants harboured at least one sequence shared across blood and lung, supporting the migration of clonally-expanded cells between sites. The extent of blood proviral diversity on ART was also a strong indicator of diversity in lung (Spearman's ρ = 0.98, p<0.0001). For three participants, insufficient lung sequences were recovered to reliably investigate genetic compartmentalization. Of the remainder, only two participants showed statistically significant support for compartmentalization when analysis was restricted to distinct proviruses per site, and the extent of compartmentalization was modest in both cases. When all within-host sequences (including duplicates) were considered, the number of compartmentalized datasets increased to four. Thus, while a subset of individuals harbour somewhat distinctive proviral populations in blood and lung, this can simply be due to unequal distributions of clonally-expanded sequences. For two participants, on-ART proviruses were also phylogenetically analyzed in context of plasma HIV RNA populations sampled up to 18 years prior, including pre-ART and during previous treatment interruptions. In both participants, on-ART proviruses represented the most ancestral sequences sampled within-host, confirming that HIV sequences can persist in the body for decades. This analysis also revealed evidence of re-seeding of the reservoir during treatment interruptions. Results highlight the genetic complexity of proviruses persisting in lung and blood during ART, and the uniqueness of each individual's proviral composition. Personalized HIV remission and cure strategies may be needed to overcome these challenges.


Evaluation of an iron specific checklist for the assessment of dietary iron intake in pregnant and postpartum women.
This study developed and validated an iron checklist for assessing dietary iron intake of pregnant and postpartum women. The checklist included 65 food and drink items. Iron intake measured by the checklist was compared with a diet history interview by paired t test and by the Bland-Altman method in 54 pregnant women. We then used the checklist to prospectively assess iron intake in a separate group of women in late pregnancy (n = 179) and at 6 mo postpartum (n = 177). The ability of the checklist to predict iron status was evaluated. There was no difference in reported mean iron intakes between the checklist and the diet history and there were good correlations between iron intake estimated from both methods (r = 0.69, P < 0.001 for food alone, r = 0.99, P < 0.001 for food plus supplements). However, the agreement between the two methods at an individual level was low. Pregnant women with low iron intake (lower than the recommended dietary intake) had lower serum ferritin levels (9.7 versus 14.5 microg/L, P < 0.001) and higher risk of iron deficiency (67.5% versus 34.9%, P < 0.0001) compared with women with adequate iron intake (at least the minimum recommended dietary intake), but these differences disappeared when women taking iron supplements were excluded. There was no association between iron intake and serum ferritin at 6 mo postpartum or between iron intake and hemoglobin levels at the end of pregnancy or at 6 mo postpartum. This simple iron checklist is a useful tool in describing iron intake of population samples of pregnant women but has limited ability to predict iron status.


Protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila.
The protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila CW strain was explored by observing the clinical signs and histopathology, measuring the cumulative mortality, serum biochemical and non-specific immune indicators, and intestinal microbiota in this study. The cumulative survival rate of the cinnamaldehyde within 14 days was significantly higher than that of the challenge group, which was 70% and 20%, respectively. Compared with the challenge group, the activities of lysozyme, superoxide dismutase, and glutathione peroxidase in the treatment group were increased, while there was no significant difference in catalase activity. Compared with the challenge group, the histopathology results showed that the injury of liver, spleen, and kidney was significantly alleviated after cinnamaldehyde treatment. The results of intestinal microbiota showed that the proportion of Proteobacteria in the challenge group was significantly increased, and the proportion of Aeromonas sp. reached 30% based on the analysis of species classification level. The composition of dominant species in the treatment group was similar to the control group. In conclusion, cinnamaldehyde increased the cumulative survival rate of channel catfish infected by A. hydrophila. It could protect channel catfish through improving the non-specific immune function of channel catfish, alleviating the pathological lesions of liver, spleen, kidney, and intestine, and maintaining the relative balance of the intestinal microbiota. Therefore, cinnamaldehyde could be a candidate drug for the treatment of A. hydrophila infection.


Suburban air quality: Human health hazard assessment of potentially toxic elements in PM10.
PM10 samples were collected at two suburban locations in northern Spain, a traffic-industrial suburban (TIS) station located in the coastal city of Gijón and an industrial suburban (IS) station in Langreo, about 25 km inland. The aerosol samples were chemically analysed to determine ambient air concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Se, V and Zn. The results showed that the mean levels of As, Co, Cu, Fe, Mn, Ni, Pb and Se recorded at the IS location were higher than those at the TIS station. Mean levels of Fe and Zn in PM10 were higher than all other species at both the TIS and IS sampling sites (467 and 353 ng Fe/m3 and 46 and 282 ng Zn/m3, respectively). Human exposure to these twelve potentially toxic elements through PM10 was assessed for both children and adults using the U.S.EPA method, considering three pathways: ingestion, dermal contact and inhalation. In general, the IS location presented higher non-cancer risks than the TIS site. However, at both suburban locations, cancer and non-cancer risk values were in the acceptable range for adults, some exceptions being found. Greater health risk was estimated in the case of children. For this sector of the population, ingestion, dermal contact and/or inhalation of As, Pb and Zn in PM10 may pose a health hazard owing to possible carcinogenic/non-carcinogenic effects.


Codeine-induced hepatic injury is via oxido-inflammatory damage and caspase-3-mediated apoptosis.
Codeine (3-methylmorphine) is a known analgesic, antitussive, and antidiarrheal drug that is often abused for recreational purposes. It is metabolized in the liver via the cytochrome P450 system and thus hypothesized to induce hepatic injury especially when misused. Thus, the present study aimed at investigating changes in liver function, hepatic enzyme biomarker, proton pumps, antioxidant status, free radicals and TNF-α levels, as well as caspase 3 activities and hepatic DNA fragmentation after 6 weeks of oral codeine administration. Twenty-one male rabbits were randomized into 3 groups (n = 7). The control group had 1 ml of normal saline, while the low-dose and high-dose codeine groups received 4 and 10 mg/kg b.w of codeine respectively daily. The codeine-treated animals had significantly lower levels of serum proteins, increased activities of hepatic enzyme biomarkers and caspase 3, raised hepatic concentrations of free radicals and TNF-α, as well as increased hepatic DNA fragmentation. Codeine treatment also led to a significant decline in hepatic weight, activities of hepatic enzymatic antioxidant, Na+-K+-ATPase and Ca2+-ATPase. These alterations were more pronounced in high-dose codeine treated animals than in the low-dose group. Histopathological study showed moderate fatty degeneration of hepatic parenchyma, infiltration of the portal tract by inflammatory cells with dense collagen fibre deposition in codeine-treated animals. The present study revealed that codeine induced liver injury and hepatic DNA damage via caspase 3-dependent signaling by suppressing hepatic antioxidant status and enhancing free radical and TNF-α generation.


Potential of environmental concentrations of the musks galaxolide and tonalide to induce oxidative stress and genotoxicity in the marine environment.
Polycyclic musk compounds have been identified in environmental matrices (water, sediment and air) and in biological tissues in the last decade, yet only minimal attention has been paid to their chronic toxicity in the marine environment. In the present research, the clams Ruditapes philippinarum were exposed to 0.005, 0.05, 0.5, 5 and 50 μg/L of the fragrances Galaxolide® (HHCB) and Tonalide® (AHTN) for 21 days. A battery of biomarkers related with xenobiotics biotransformation (EROD and GST), oxidative stress (GPx, GR and LPO) and genotoxicity (DNA damage) were measured in digestive gland tissues. HHCB and AHTN significantly (p < 0.05) induced EROD and GST enzymatic activities at environmental concentrations. Both fragrances also induced GPx activity. All concentrations of both compounds induced an increase of LPO and DNA damage on day 21. Although these substances have been reported as not acutely toxic, this study shows that they might induce oxidative stress and genotoxicity in marine organisms.


Precise phase retrieval for propagation-based images using discrete mathematics.
The ill-posed problem of phase retrieval in optics, using one or more intensity measurements, has a multitude of applications using electromagnetic or matter waves. Many phase retrieval algorithms are computed on pixel arrays using discrete Fourier transforms due to their high computational efficiency. However, the mathematics underpinning these algorithms is typically formulated using continuous mathematics, which can result in a loss of spatial resolution in the reconstructed images. Herein we investigate how phase retrieval algorithms for propagation-based phase-contrast X-ray imaging can be rederived using discrete mathematics and result in more precise retrieval for single- and multi-material objects and for spectral image decomposition. We validate this theory through experimental measurements of spatial resolution using computed tomography (CT) reconstructions of plastic phantoms and biological tissues, using detectors with a range of imaging system point spread functions (PSFs). We demonstrate that if the PSF substantially suppresses high spatial frequencies, the potential improvement from utilising the discrete derivation is limited. However, with detectors characterised by a single pixel PSF (e.g. direct, photon-counting X-ray detectors), a significant improvement in spatial resolution can be obtained, demonstrated here at up to 17%.


Synergy between sequence and size in large-scale genomics.
Until recently the study of individual DNA sequences and of total DNA content (the C-value) sat at opposite ends of the spectrum in genome biology. For gene sequencers, the vast stretches of non-coding DNA found in eukaryotic genomes were largely considered to be an annoyance, whereas genome-size researchers attributed little relevance to specific nucleotide sequences. However, the dawn of comprehensive genome sequencing has allowed a new synergy between these fields, with sequence data providing novel insights into genome-size evolution, and with genome-size data being of both practical and theoretical significance for large-scale sequence analysis. In combination, these formerly disconnected disciplines are poised to deliver a greatly improved understanding of genome structure and evolution.


Acetylcholine and tachykinin receptor antagonists attenuate wood smoke-induced bronchoconstriction in guinea pigs.
To study the mechanisms of wood smoke-induced bronchoconstriction, we measured total lung resistance (RL) and dynamic lung compliance (Cdyn) in anesthetized and mechanically ventilated guinea pigs. Airway exposure to various doses of wood smoke (lauan wood; 5, 10, and 15 breaths) resulted in a dose-dependent increase in RL and decrease in Cdyn. The smoke-induced changes in RL and Cdyn were significantly attenuated by pretreatment with atropine, CP-96,345 [(2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-aza bicyclo(2.2.2.)-octan-3-amine; a tachykinin NK1 receptor antagonist], and SR-48,968 [(S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophen yl)-butyl)benzamide; a tachykinin NK2 receptor antagonist] in combination, atropine alone, and SR-48,968 alone, but were not significantly affected by pretreatment with the inactive enantiomers of CP-96,345 and SR-48,968, CP-96,345 alone, indomethacin (a cyclooxygenase inhibitor), and MK-571 [((3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl((3-dimethyl amino-3-oxo-propyl)thio)methyl)propanoic acid; a leukotriene D4 receptor antagonist]. The activity of airway neutral endopeptidase, a major enzyme for tachykinin degradation, was not significantly influenced by wood smoke during the development of bronchoconstriction. We conclude that: (1) both cholinergic mechanisms and endogenous tachykinins, but not cyclooxygenase products or leukotriene D4, play an important role in the acute bronchoconstriction induced by wood smoke, and (2) the contribution of tachykinins to this airway response is primarily mediated via the activation of tachykinin NK2 receptors, but is not associated with inactivation of the airway neutral endopeptidase.


Synergistic bactericidal effects of pairs of photosensitizer molecules activated by ultraviolet A light against bacteria in plasma.
The current approach to reducing bacterial contamination in blood transfusion products is through detection or pathogen reduction methods, some of which utilize ultraviolet (UV) light photosensitizers. A small number of photosensitizers are being used as single agents in combination with UV light, but their efficacy can be limited against some pathogens. Benzophenone (BP) and vitamins B1, B6, and K3 have been identified as effective UVA photosensitizers for inactivation of bacteria. We evaluated whether combining pairs of photosensitizers in this group would have synergistic bactericidal effects on Gram-negative and Gram-positive bacteria. Bacteria species of Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Klebsiella pneumoniae were mixed with 0 to 100 mM concentrations of photosensitizers and exposed to UVA irradiation at 18 J/cm2 to assess their bactericidal effects. Single photosensitizers irradiated with UVA produced a range of bactericidal activity. When combined in pairs, all demonstrated some synergistic bactericidal effects with up to 4-log reduction above the sum of activities of individual molecules in the pair against bacteria in plasma. Photosensitizer pairs with BP had the highest synergism across all bacteria. With vitamin K3 in the pair, synergism was evident for Gram-positive but not for Gram-negative bacteria. Vitamin B1 and vitamin B6 had the least synergism. These results indicate that a combination approach with multiple photosensitizers may extend effectiveness of pathogen reduction in plasma. Combining photosensitizers in pathogen reduction methods could improve bactericidal efficacy and lead to use of lower concentrations of photosensitizers to reduce toxicities and unwanted side effects.


Adjunctive chemotherapy to radical radiation therapy in the treatment of advanced nasopharyngeal carcinoma.
Sixty-eight consecutive patients with previously untreated nasopharyngeal carcinoma (NPC) with advanced cervical lymph nodal metastases were studied retrospectively for the effectiveness of combining chemotherapy with radical radiation therapy (RT). In 1981 and 1982, 36 patients were treated with radical radiation therapy alone (arm 1). In 1983, 13 patients were given 2 courses of VBMF prior to RT (arm 2). In 1984, 19 patients were given radical RT sandwiched between 2 courses of PVBMF before and 2 after (arm 3). The three arms were comparable in patient characteristics with similar stages of the disease, sex, age distribution, and rates of completion of the prescribed treatments. There was no significant difference in actuarial or disease-free survival between arm 1 and 3 or arm 2 and 3, but arm 1 compared favorably with arm 2 in actuarial survival (X2 = 9.533, p = 0.002). The distant relapses in arms 2 and 3 occurred at significantly shorter times after diagnosis than those in arm 1 (t = 4.1083, p = 0.0001). Postponement of radiation therapy by chemotherapy might have accounted for the earlier distant relapses in arm 2 and 3. Radiation therapy alone given in radical dose had been demonstrated to achieve significantly more complete responses in cervical nodal metastases than either forms of chemotherapy (VBMF or PVBMF) given just two courses prior to radiation therapy (p less than 0.00003). More controlled clinical trials must be completed before acceptance of chemotherapy as part of a standard radical treatment for advanced nasopharyngeal carcinoma with advanced cervical lymph nodal metastases. In all future trials, closer integration in time sequence between the two treatment modalities is indicated. Meanwhile cervical nodal status (CR vs, PR plus NR) at the end of any treatment was shown to be of paramount prognostic significance.


[Sonography of the Joints - Step by Step].
The availability of modern ultrasound machines with high resolution scanners and sensitive Doppler functions facilitates the investigation of joints and tendons in different conditions. It should be the first diagnostic step in musculoskeletal diseases which is done in a structured sequence according to official guidelines.


The thermodynamics of bovine and porcine insulin and proinsulin association determined by concentration difference spectroscopy.
Difference spectroscopy was used to determine the equilibrium constants and thermodynamic parameters for the monomer-dimer association of bovine and porcine insulin and bovine proinsulin at pH 2.0 and 7.0. At pH 2 delta G degree 25, delta S degree, and delta H degree for dimerization of bovine insulin were found to be -6.6 kcal/mol, -18 cal/mol-deg, and -12 kcal/mol, respectively. Porcine insulin behaved similarly to bovine insulin in its dimerization properties in that delta G degree 25, delta S degree, and delta H degree were found to be -6.8 kcal/mol, -14 cal/mol-deg, and -11 kcal/mol, respectively. At pH 7 delta G degree 25, delta S degree, and delta H degree for dimerization of bovine insulin were found to be -7.2 kcal/mol, -16 cal/mol/deg, and -12 kcal/mol, respectively. At pH 7.0 delta G degree 25, delta S degree, and delta H degree for dimerization of porcine insulin were -6.7 kcal/mol, -11.6 cal/mol-deg, and -10 kcal/mol, respectively. The similarity in the thermodynamic parameters of both insulin species at the different pH's suggests that there are minimal structural changes at the monomer-monomer contact site over this pH range. The dimerization of both insulin species is under enthalpic control. This may suggest that the formation of the insulin dimer is not driven by hydrophobic bonding but, rather, is driven by the formation between subunits of four hydrogen bonds in an apolar environment. At pH 2 delta G degree 25, delta S degree, and delta H degree for dimerization of bovine proinsulin were found to be -5.3 kcal/mol, -26 cal/mol-deg, and -13 kcal/mol, respectively. At pH 7 delta G degree 25, delta S degree, and delta H degree for dimerization of proinsulin were -5.9 kcal/mol, -4.2 cal/mol-deg, and -7.2 kcal/mol, respectively. Although the presence of the C-peptide on proinsulin does not drastically affect the overall free energy change of dimer formation (as compared to insulin), the other thermodynamic parameters are rather drastically altered. This may be because of electrostatic interactions of groups on the C-peptide with groups on the B-chain which are near the subunit contact site in the insulin dimer.


Measurement of post-operative pain and narcotic administration in infants using a new clinical scoring system.
We developed a clinical neurologic and behavioral scoring system composed of 10 items to measure the post-operative pain levels in infants: (1) sleep during preceeding hour, (2) facial expression of pain, (3) quality of cry, (4) spontaneous motor activity, (5) Spontaneous excitability, (6) flexion of fingers and toes, (7) sucking, (8) global evaluation of tone, (9) consolability and (10) sociability. Using this system, a group of infants ranging from one to seven months in age and undergoing minor surgical procedures was studied. The infants were randomly assigned to two groups: Group I received Fentanyl intravenously (3 micrograms/kg) prior to surgery, and Group II received a placebo. The infants then were studied post-operatively in the recovery room at 30, 60, 90 and 120 min intervals. Over the entire post-operative observation period, 54% of the infants in Group I had satisfactory analgesia compared to 18% in Group II. There were no significant differences in Group I and Group II in oxygenation, carbon dioxide elimination, blood pressure, heart rate or temperature.


Multivariate prediction of major adverse cardiac events after 9914 percutaneous coronary interventions in the north west of England.
To develop a multivariate prediction model for major adverse cardiac events (MACE) after percutaneous coronary interventions (PCIs) by using the North West Quality Improvement Programme in Cardiac Interventions (NWQIP) PCI Registry. All NHS centres undertaking adult PCIs in north west England. Retrospective analysis of prospectively collected data on 9914 consecutive patients undergoing adult PCI between 1 August 2001 and 31 December 2003. A multivariate logistic regression analysis was undertaken, with the forward stepwise technique, to identify independent risk factors for MACE. The area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness of fit statistic were calculated to assess the performance and calibration of the model, respectively. The statistical model was internally validated by using the technique of bootstrap resampling. MACE, which were in-hospital mortality, Q wave myocardial infarction, emergency coronary artery bypass graft surgery, and cerebrovascular accidents. Independent variables identified with an increased risk of developing MACE were advanced age, female sex, cerebrovascular disease, cardiogenic shock, priority, and treatment of the left main stem or graft lesions during PCI. The ROC curve for the predicted probability of MACE was 0.76, indicating a good discrimination power. The prediction equation was well calibrated, predicting well at all levels of risk. Bootstrapping showed that estimates were stable. A contemporaneous multivariate prediction model for MACE after PCI was developed. The NWQIP tool allows calculation of the risk of MACE permitting meaningful risk adjusted comparisons of performance between hospitals and operators.


Characterization of insulin-like growth factor I receptors and growth effects in human lung cancer cell lines.
Small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines were studied for insulin-like growth factor I (IGF-I) receptor expression and with regard to the influence of IGF-I on cell proliferation. IGF-I receptors on the cells were characterized by competitive binding assays, chemical crosslinking and northern blot hybridization of IGF-I receptor mRNA. All SCLC and NSCLC cell lines showed specific IGF-I binding sites with an affinity (KD) of 0.69-5.21 nM. The amount of binding sites ranged from 59 fmol/mg to 1230 fmol/mg protein. The IGF-I binding was inhibited by the IGF-I receptor antibody (alpha-IR-3). Northern blot hybridization indicated that IGF-I receptor mRNA was being produced by all SCLC and NSCLC cell lines. We used the soft-agarose clonogenic assay to evaluate the influence of IGF-I on the in vitro proliferation of the cells. Our results have shown that IGF-I stimulates the growth of all tested cell lines ranging from a factor of 1.6 to 4.2 in SCLC and from 1.1 to 2.7 in NSCLC. The data indicate that the IGF-I receptor thus appears to be the common pathway for the mitogenic activity of IGF-I and IGF-II with regard to human lung cancer cells.


Dietary immunostimulants reduced infectivity of Diplostomum spp. eye fluke in common carp, Cyprinus carpio L.
Juvenile common carp Cyprinus carpio L. (5.52 ± 1.66 cm, TL) were fed on four diets containing either beta-glucan (MacroGard, 1 g kg -1), nucleotides (Optimûn, 0.2 g kg - 1), chitosan (deacetylated chitin ≥75% shrimp shells, 10 g kg -1) or a basal control diet for 35 days to test whether these so-called "immunostimulants" could affect eye fluke Diplostomum spp. infection success. The immunostimulants diets reduced the number of eye fluke infecting the eyes of C. carpio, with significantly higher infections in the control diet (4.78 ± 1.27) compared with the chitosan (2.08 ± 0.87), nucleotide (2.98 ± 1.01), and beta-glucan (1.41 ± 0.79) diets. To our knowledge, this is the first study to provide evidence that beta-glucan, nucleotides, and chitosan diets can aid against a Diplostomum infection and provides valuable preliminary knowledge on the use of immunostimulants to ameliorate parasitic infections.


Effect of up to 30-days of storage at different temperatures on detection of feline kidney injury molecule-1 in urine.
In humans, kidney injury molecule-1 (KIM-1) is a biomarker of acute kidney injury that can be quantified in urine. Preliminary investigation in cats with experimentally induced acute kidney injury showed that KIM-1 urine concentration correlated with kidney injury histopathology scores. A lateral flow assay (LFA) has recently become available for patient-side feline KIM-1 measurement. In vitro parameters of the assay have not yet been determined. The objectives of this study were to determine detection of KIM-1 in urine stored at different temperatures over time, to establish the linear range of the LFA, and to assess the intra-assay repeatability of measurements. RESULTS: Ten urine samples with a range of KIM-1 concentrations were stored at room temperature (22o C), 4o C or -20o C, and tested with the LFA on days 0, 1, 2, 3, 7, 14, and 30. The concentration of KIM-1 in samples was not significantly different from the day 0 value, except one sample that had been stored for 30 days at room temperature yielded a significantly higher value. The assay results had a correlation coefficient of 0.922. The mean coefficient of variation for all samples was 15.7%. The slope of the curve of expected versus measured values in samples diluted two-fold nine times was 0.908, and results were linear over all dilutions. The LFA for feline KIM-1 yields consistent results from stored urine samples. These characteristics will allow for KIM-1 to be measured retrospectively if immediate testing is not feasible. Within assay precision was high, and linearity over 9 logs of dilution suggests suitability for a range of subclinical and clinical kidney injuries.


Hinge prostheses in the revision of unicompartmental knee replacement: a descriptive analysis of data from the national joint registry for England, Wales and Northern Ireland.
Unicompartmental knee replacement (UKR) is an effective surgical strategy in patients with isolated medial or lateral compartment osteoarthritis. Study aims were to (1) describe the epidemiology of patients undergoing revision of UKR to a hinge knee replacement (HKR); (2) identify factors influencing time to revision; (3) evaluate HKR survival. An analysis of National Joint Registry data was undertaken, exploring revision of UKR to HKR between 2007 and April 2021. Descriptive analysis of eligible patients and Cox Regression to identify key determinants of time to revision were performed. Failure of HKR post-revision was assessed using survival analysis. 111 patients underwent revision of UKR to HKR. Median age at revision was 70 years and most common indications were instability (n = 42) and infection (n = 22). The most common implant was a rotating HKR. Significant independent factors associated with earlier revision were periprosthetic fracture (p = 0.03) and malalignment (p = 0.03). Progressive osteoarthritis (p = 0.01) and higher ASA grades (3: p = 0.01, 4: p < 0.01) delayed time to revision; patient sex and age were not significant factors. Ten patients required subsequent re-revision; median age at re-revision was 61 years. HKR revised from UKR had an 89.3% revision-free risk at 5 years. Male sex (p < 0.01) and younger age (p < 0.01) were associated with re-revision. Factors associated with time to revision may be used to counsel patients prior to UKR. The survivorship of the HKR of 89.3% at 5 years is concerning and careful consideration should be given when using this level of constraint when revising UKR in younger or male patients.


Decreased insular and increased midbrain activations during decision-making under risk in adolescents with excess weight.
Functional magnetic resonance imaging (fMRI) was used to explore the brain substrates of decisions under risk in excess weight adolescents. Decreased activations of the brain regions signaling risk (orbitofrontal cortex [OFC], insula) were expected during anticipation of higher rewards and increased activations of the brain regions involved in reward processing (OFC, striatum) were expected after reward receipt in excess weight adolescents compared to normal weight controls. Fifty-two adolescents (age range 12-17), classified in three groups as a function of BMI: obese (n = 21), overweight (n = 15), or normal weight (n = 16) performed the Risky-Gains task as described by Paulus et al. in the fMRI scanner. Excess weight adolescents, compared to normal weight controls, showed decreased left insular and increased midbrain activations during anticipation of risky choices. In addition, excess weight adolescents showed increased activations of the inferior frontal gyrus, parahippocampus, thalamus, and posterior brain regions after reward receipt. Adolescents with excess weight showed reduced activations in brain regions signaling risk and increased activations in regions signaling reward during anticipation of decisions involving risk and reward. In addition, post-decision reward outcomes produced increased activations of regions involved in emotional salience in excess weight adolescents versus controls.


Atropoisomeric (P,N) ligands for the highly enantioselective Pd-catalyzed intramolecular asymmetric α-arylation of α-branched aldehydes.
Three-in-one: a short synthetic route readily gives access to a new class of chiral (P,N) ligands characterized by three distinct elements of chirality. These ligands are highly enantioselective in the challenging Pd-catalyzed intramolecular asymmetric α-arylation of α-branched aldehydes.


Distinct characteristics of asymmetric magnetic reconnections: Observational results from the exhaust region at the dayside magnetopause.
Magnetic reconnection plays a key role in the conversion of magnetic energy into the thermal and kinetic energy of plasma. On either side of the diffusion region in space plasma, the conditions for the occurrence of reconnections are usually not symmetric. Previous theoretical studies have predicted that reconnections under asymmetric conditions will bear different features compared with those of symmetric reconnections, and numerical simulations have verified these distinct features. However, to date, the features of asymmetric reconnections have not been thoroughly investigated using in situ observations; thus, some results from theoretical studies and simulations have not been tested with observations sufficiently well. Here, spacecraft observations are used in a statistical investigation of asymmetric magnetic reconnection exhaust at the dayside magnetopause. The resulting observational features are consistent with the theoretical predictions. The results presented here advance our understanding of the development of reconnections under asymmetric conditions.


Opioid detoxification via single 7-day application of a buprenorphine transdermal patch: an open-label evaluation.
Managed withdrawal (i.e., detoxification) from opioid dependence is a widespread clinical procedure that is a necessary step for those pursuing abstinence. Buprenorphine is one effective detoxification treatment, however, consensus regarding effective detoxification procedures is lacking. This study evaluated the efficacy of a buprenorphine transdermal formulation (i.e., patch) in suppressing opioid withdrawal, its safety and tolerability, and its biodelivery when applied for 7 days. Physically dependent opioid (heroin) users (n = 12) completed a 10-day opioid detoxification in a residential research unit. Each received a single patch application that remained in place for 7 days. Blood samples were drawn prior to patch application and once daily thereafter. Assessments, four times daily, included: the amount of rescue medications ordered to treat withdrawal discomfort; self-report and observer ratings of opioid withdrawal and agonist effects; and vital sign measures. Overall, the patch appeared safe and well-tolerated. Buprenorphine plasma levels peaked 48 h after patch application at 0.59 ng/ml. Indices of withdrawal (self-reports, observer ratings, rescue medication) were significantly reduced within 24 h of patch application, continued to decline thereafter, and did not reappear following patch removal. This study confirms that transdermal buprenorphine is safe and clinically effective, and suggests that a 7-day application may provide an effective and comfortable means of detoxification. This patch formulation would appear to be a useful opioid detoxification treatment by reducing compliance concerns, and administering buprenorphine in a formulation less likely to be diverted to illicit use.


Population ecology of carabid cave beetles.
The population ecology of three species of obligate cave dwelling (i.e., troglobitic) carabid beetles, Neaphaenops tellkampfi, Pseudanophthalmus menetriesi and P. pubescens, was studied in five cave habitats in west central Kentucky. Population size, timing of teneral occurrence, sex ratio, proportion of ovigerous females and clutch size were monitored in 12 populations. The data indicate that cave carabid beetles undergo density fluctuations at the local population (subpopulation) level which are intermediate in severity to those observed in surface dwelling carabid species. However, composite populations of N. tellkampfi show overall density fluctuations which are not statistically different in severity from those of more stable surface carabid species. It appears that spatial heterogeneity has a damping effect on density fluctuations in N. tellkampfi over the geographic area studied. A similar explanation has been offered for the more stable surface carabid species.The predictable nature of the cave environment and the reduced number of selection pressures in cave habitats has permitted us to consider evolutionary patterns in these cave carabid species as they relate to differences in ecology. Two major adaptive pathways can be inferred from the population data of this study. Pseudanophthalmus menetriesi and P. pubescens appear to have undergone divergent evolution for habitat specialization in mesic and riparian habitats respectively. Significant life history differences between these two species appear to be related to the characteristics of mesic vs. riparian habitats. Neaphaenops tellkampfi is specialized to prey on cave cricket (Hadenoecus subterraneus) eggs and nymphs, resources which are highly seasonal and become rare in the fall. As a result N. tellkampfi has retained some generalist traits in feeding and in habitat utilization. Its life history characteristics are more variable than those of the Pseudanophthalmus spp. and appear to allow N. tellkampfi to exploit two distinct subniches in the depauperate cave environment.


Changes in health and sleep quality after anti-retroviral treatment modification in Japanese people living with HIV.
Anti-retroviral treatment (ART) modification for treatment simplification is performed in virologically controlled people living with Human Immunodeficiency Virus (PLWH). However, studies on the impact of these stable treatment modifications on health-related quality of life (HRQoL) measured using patient-reported outcomes (PROs) in clinical practice are scarce; this was the focus of this study. PLWH who visited Teikyo University Hospital between October 2019 and March 2021, and whose ART was changed to a newly recommended single-tablet regimen for treatment simplification, were included in the study. HRQoL and sleep quality were evaluated using the Short-Form (SF) 8 and Pittsburgh Sleep Quality Index (PSQI) global score, respectively, at two time points: before and after treatment modification. Comorbidities, duration of Human Immunodeficiency Virus diagnosis, ART initiation, ART regimens, and blood test data before and after treatment were assessed. The SF-8 was used to calculate the physical component summary (PCS) and mental component summary (MCS) scores. Forty-nine patients (all male) were included into the study. There was no change in the PCS score before and after ART modification. The MCS score significantly improved from 48.50 ± 6.56 to 50.76 ± 4.37 (p = 0.0159). Thirteen patients' ARTs were changed to dolutegravir/lamivudine. Their HRQoL and sleep quality changes were further analyzed. Their MCS and PSQI scores had improved significantly. Thirty patients' ARTs were changed to bictegravir/tenofovir alafenamide/emtricitabine; however, there were no significant changes in their HRQoL or PSQI score. ART modification for treatment simplification based on PROs may improve the HRQoL of PLWH.


Mass mortality associated with koi herpesvirus in common carp in Iraq.
Koi herpesvirus disease is a serious disease affecting both wild and common carp species in different continents throughout the world. Based on pathological and molecular findings, we document the presence of koi herpesvirus disease in Iraq as a cause of mass mortality among the common carp of the Tigris river. On a macroscopic level, the fish exhibited variably sized skin ulcerations throughout the entire trunk. The gills showed variable degrees of discoloration with an increased amount of slimy mucus. Microscopically, degeneration and necrosis with infiltration of a heterogenous population of inflammatory cells characterized different organs, primarily the skin and gills, with occasional intranuclear inclusion bodies that are consistent with koi herpesvirus disease. A semi-nested PCR assay coupled with sequencing confirmed the pathological diagnosis. Genotyping and sequence analysis of the TK gene, ORF 136 and markers I and II identified the isolated CyHV-3 as variant A1 of the Asian genotype TUSMT1 (J strain) displaying the I++II+ allele.


Novel plasmid conferring kanamycin and tetracycline resistance in the turkey-derived Campylobacter jejuni strain 11601MD.
In Campylobacter spp., resistance to the antimicrobials kanamycin and tetracycline is frequently associated with plasmid-borne genes. However, relatively few plasmids of Campylobacter jejuni have been fully characterized to date. A novel plasmid (p11601MD; 44,095nt) harboring tet(O) was identified in C. jejuni strain 11601MD, which was isolated from the jejunum of a turkey produced conventionally in North Carolina. Analysis of the p11601MD sequence revealed the presence of a high-GC content cassette with four genes that included tet(O) and a putative aminoglycoside transferase gene (aphA-3) highly similar to kanamycin resistance determinants. Several genes putatively involved in conjugative transfer were also identified on the plasmid. These findings will contribute to a better understanding of the distribution of potentially self-mobilizing plasmids harboring antibiotic resistance determinants in Campylobacter spp. from turkeys and other sources.


Characterization of over-expressed alkaline phosphodiesterase I in tumour-derived fibroblasts from patients with neurofibromatosis.
Alkaline phosphodiesterase I from cultured fibroblasts from patients with neurofibromatosis was partially purified and characterized following extraction with Triton X-100, and fractionation with high-performance liquid chromatography. Some properties were compared with the enzyme extracted from normal-appearing fibroblasts. The isoelectric points of both the tumour and normal-appearing cell enzymes were 6.0. The enzyme required Zn2+ for its activity, was heat labile, and nicked superhelical covalently closed circular phi X174 DNA. The activity was inhibited by GTP, DTT and EDTA. The native molecular weight of alkaline phosphodiesterase I was determined to be 430,000. No differences were found in properties of the tumour-derived and normal cell enzymes. On purification it was observed that the peak pattern of enzyme activity corresponded to that of 125 kDa protein, which was more abundant upon SDS-PAGE analysis in tumour cells than in normal cells. The most active fraction of isoelectric focusing, which was performed using disulfide cross-linked polyacrylamide gel, was used to produce an antibody. The bands of 125, 60 and 40 kDa were immuno-stained in tumour cell preparation. These results indicate that alkaline phosphodiesterase I, of which the molecular weight is probably 125 kDa, is over-expressed in tumour-derived fibroblasts from neurofibromatosis patients.


Primary localized amyloidosis of the small intestine presenting as an intestinal pseudo-obstruction: report of a case.
A 47-year-old man with primary amyloidosis confined to the small intestine is reported. Thickening of the folds and multiple polypoid protrusions were found in the duodenum by upper gastrointestinal endoscopy. Because the patient presented with a persistent intestinal pseudo-obstruction, partial jejunectomy was performed. Histological examination of the resected tissue revealed massive deposits of amyloid throughout the jejunal wall. Neither a predisposing condition nor any other sites of deposition were found, and primary amyloidosis of the small intestine was diagnosed. This rare form of amyloid deposition should be recognized so that an early diagnosis can be made.


Beta-blocking potency of mepindolol and pindolol against isoproterenol-induced inotropic and chronotropic responses in guinea pig atria.
The beta-blocking potencies of mepindolol and pindolol were determined in guinea pig right atria (heart rate) and paced left atria (contractile force) in vitro. Neither agent showed selectivity for blocking rate responses induced by isoproterenol. The pA2 (95% confidence interval) values determined for mepindolol against rate and force responses induced by isoproterenol were 9.96 (9.91-10.01) and 9.52 (9.44-9.60), respectively, and for pindolol, 9.20 (9.15-9.25) and 8.85 (8.76-8.94). Mepindolol was approximately 6.5 times as potent as pindolol. The present evidence does not support the hypothesis of subpopulations of beta-receptors subserving inotropic and chronotropic responses.


Modification of the effects of continuous low dose rate irradiation by concurrent chemotherapy infusion.
The combined effects of continuous low dose rate irradiation (CLDRI) and concurrent infusion of bleomycin, cyclophosphamide, cis-platinum, 5-fluorouracil, actinomycin D, and mitomycin C were studied in the SCC VII/SF tumor, a squamous cell carcinoma and the jejunal crypt cells in the mouse. For the SCC VII/SF tumor, enhanced cell killing was seen with each of the six drugs when infused concurrently with CLDRI; the greatest enhancement was seen with mitomycin C and cis-platinum. For the jejunal crypt cells, enhanced cell killing was seen primarily with bleomycin. At a dose of 20 Gy, the dose effect factor (DEF) ranged from 1.13-1.64 for the SCC VII/SF tumor and 0.92-1.19 for the jejunal crypt cells. Our results suggest a therapeutic gain with concurrent CLDRI and chemotherapy infusion for five of the six chemotherapeutic drugs studied with the exception of bleomycin.


Psychotic-Like Experiences Associated with Sleep Disturbance and Brain Volumes in Youth: Findings from the Adolescent Brain Cognitive Development Study.
Sleep disturbance is characteristic of schizophrenia and at-risk populations, suggesting a possible etiological role in psychosis. Biological mechanisms underlying associations between sleep and psychosis vulnerability are unclear, although reduced sleep-regulatory brain structure volumes are a proposed contributor. This study is the first to examine relationships between psychotic-like experiences (PLEs; subclinical symptoms reflecting psychosis vulnerability/risk), sleep, and brain volumes in youth. Brain volumes of five sleep-related structures were examined in relation to PLEs and difficulties initiating and maintaining sleep (DIMS) in 9260 9-11 year-olds participating in the Adolescent Brain Cognitive Development (ABCD) study. Analytic models examined relationships between DIMS, PLEs, and brain volumes, as well as DIMS as a mediator of brain volume-PLEs relationships. Although sleep regulation structures (i.e., thalamus, basal forebrain, hypothalamus) were of primary interest, other potentially-relevant structures to sleep-related functioning and psychosis (i.e., hippocampus, amygdala) were also examined. PLEs were associated with increased DIMS as well as reduced volume in some, but not all, brain structures, including the thalamus and basal forebrain in children. DIMS was also associated with reduced left thalamus volume in youth. Increased DIMS partially, statistically mediated the relationship between left thalamic volume and PLEs, although the effect was relatively small. Results highlight left thalamic volume as a potential neural mechanism underlying sleep disturbances and PLEs in childhood. Future studies should assess causal relationships between sleep, PLEs, and brain structure across adolescent development, interactions with other psychosis risk factors, and the role of sleep interventions in prevention of psychosis and a range of psychiatric conditions across the lifespan.


Subjective burden in mothers of speech-impaired children.
Evaluation of perceived subjective burden in mothers of speech-impaired children against the presence or absence of an emotional disorder. 89 mothers (age 33.3 +/- 5.5 years, range: 19.6-43.8 years) of 89 preschool children (23 girls, 66 boys, age: 3.9 +/- 1.5 years, range: 1.6- 7.1 years) with specific speech impairment were investigated. German versions of the Hospital Anxiety and Depression Scale (HADS) and the Burden Scale for Family Caregivers (BSFC) were applied. 11% of the mothers met criteria for a depressive disorder (normal controls: 2.5%; p = 0.008). Twenty-eight percent of the mothers met criteria for anxiety disorders (normal controls: 9.6%; p = 0.000). The HADS depression subscore and the BSFC correlate with r = 0.75. The HADS anxiety subscore and the BSFC correlate with r = 0.59. Results suggest the need for routine clinical assessment of mothers' well-being when their children are affected by speech impairment.