A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits.
Leukocytes have been shown to play an important role in the development of isolated organ injury after experimental ischemia and reperfusion. To examine the role of leukocytes in generalized ischemia-reperfusion injury we used the MAb 60.3 (directed to the human leukocyte adherence glycoprotein, CD18) to block leukocyte adherence functions in a rabbit model of hemorrhagic shock and resuscitation. In control animals subjected to 1 h of shock (mean blood pressure 45 torr and mean cardiac output 30% of baseline) followed by resuscitation, only 29% survived 5 d. All had gross and histologic evidence of injury to lungs, liver, and gastrointestinal mucosa. In contrast, 100% of the MAb 60.3-treated animals survived 5 d (P less than 0.01) and organ injury was absent or markedly attenuated. The control animals also had a persistent acidosis, lost more weight, and had evidence of continued gastrointestinal bleeding in contrast to MAb 60.3-treated animals. We conclude that increased leukocyte adhesiveness plays an important role in the development of multiple organ injury and death after generalized ischemia-reperfusion and that this injury may be significantly reduced by blocking leukocyte adherence functions with the MAb 60.3.


An efficient Lamb wave-based virtual refined time-reversal method for damage localization in plates using broadband measurements.
This study proposes a modified virtual time-reversal (VTR) algorithm for baseline signal-free damage detection in plate-like structures. The physical actuation and sensing of Lamb waves are performed using a broadband Gaussian excitation instead of the conventional narrowband modulated tone burst excitations. The forward response and the reconstructed signal due to the time-reversal process for a narrowband input signal are then constructed virtually using the broadband transfer function. The method eliminates the possibility of numerical errors encountered in the conventional VTR method based on narrowband excitations. It is also more efficient than the traditional VTR algorithm because it can probe at multiple excitation frequencies using a single measurement for each sensing path. This modified VTR algorithm is employed in the recently developed refined time-reversal method (RTRM), which uses an extended signal length of the reconstructed signal for computing damage index (DI) and probes the structure at the best reconstruction frequency. The new method is termed the virtual refined time-reversal method (VRTRM). The DIs based on the VRTRM are used in the reconstruction algorithm for probabilistic inspection of defects to achieve baseline signal-free localization of damages. The efficacy of the proposed VRTRM for damage localization is experimentally verified with the established technique RTRM. Experiments are performed in an aluminium plate equipped with a network of surface-bonded piezoelectric patch transducers to illustrate the conventional VTR's pitfalls and the modified VTR's accuracy for a single mass damage scenario. The results show that the proposed VRTRM is as accurate as the established technique RTRM in estimating the reconstructed signals and localizing a block mass damage. Finally, the VRTRM is shown to localize in a dual damage scenario with excellent accuracy. In contrast, the conventional main mode-based VTR method fails to localize the damages with or without single-mode tuning.


Pleasure or utility? Different conditions for boys and girls with disabilities in information and communication technology.
This study focuses on differences between the ways in which we look at girls' and boys' computer activities. It is evident that the gender varieties per se generate different conditions for boys and girls. Generally, children with disabilities have great difficulty defining their needs and wishes. Pedagogues, habilitation staff and parents are needed as support for both boys' and girls' development. If technology is to be part of this development, we must pay attention to it. Research within this area highlights the differences and patterns that occur. The study stresses the expectations and experiences that parents of children with disabilities have of computer-based activities for their children, with a focus on gender-related issues.


Therapeutic effect of Yokukansan on social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice.
In patients with dementia including Alzheimer's disease, hallucinations, agitation/aggression and irritability are known to frequently occur and as distressing behavioral and psychological symptoms of dementia (BPSD). On the basis of the evidence on clinical efficacy and safety of Yokukansan, a traditional Japanese herbal medicine, on BPSD, in the present study, Yokukansan was examined in the therapeutic effects on social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice. Yokukansan was p.o. administered for 7 days as a drinking water to isolated mice fed a zinc-deficient diet for 10 days, which exhibited aggressive behavior, and isolated pair-fed mice fed a control diet of the amount consumed by zinc-deficient mice for 10 days, which exhibited aggressive behavior. Aggressive behavior was evaluated by the resident-intruder test. Yokukansan (312 mg/kg/day) attenuated both aggressive behaviors of zinc-deficient and pair-fed mice. Because Yokukansan can suppress abnormal glutamatergic neuron activity, MK-801, an N-methyl-D-aspartate (NMDA) receptor blocker, and aminooxyacetic acid (AOAA), a γ-amino butyric acid (GABA) transaminase blocker, were also examined in the effects on social isolation-induced aggressive behavior. MK-801 (0.1 mg/kg) or AOAA (23 mg/kg) was i.p. injected into isolated aggressive mice. Thirty minutes later, the resident-intruder test was performed to evaluate the effect of the drugs. Both drugs attenuated aggressive behavior of zinc deficient mice, but not that of pair-fed mice. These results suggest that Yokukansan ameliorates social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice through the action against glutamatergic neurotransmitter system and other neurotransmitter systems.


Racial and ethnic differences in medication use among beneficiaries of social security disability insurance with rheumatoid arthritis.
To determine racial/ethnic differences in the use of conventional synthetic or biologic disease-modifying anti-rheumatic drugs (csDMARDs or bDMARDs, respectively) and long-term glucocorticoids (GC) or opioids among beneficiaries of the Social Security Disability Insurance (SSDI) with rheumatoid arthritis (RA) and <65 years old. Serial cross-sectional analyses of Centers for Medicare and Medicaid Services claims data (2007, 2011, and 2014) for individuals <65 years old with RA receiving SSDI Medicare and Medicaid, no longer working because they were considered disabled. Generalized estimating equation models were used to determine whether the proportion of patients who used csDMARD, bDMARD, long-term GC, and long-term opioids differed by race/ethnicity. There were 12,931; 15,033; and 15,599 participants in 2007, 2011, and 2014, respectively. The overall use of csDMARD without bDMARD among beneficiaries of the SSDI were 31.1%, 30.3%, and 29.2%; 50.2%, 51.7%, and 53.8% used bDMARDs; 37.6%, 36.1%, and 34.4% used long-term GC; and 61.1%, 63.8%, and 63.7% used long-term opioids in years 2007, 2011, and 2014 respectively. The use of csDMARDs without bDMARDs was higher and the use of bDMARDs was lower among Blacks compared to Whites (adjusted absolute difference: +3.0%, +5.0%, and +3.3% for csDMARDs without bDMARDs and -4.6%, -5.7%, and -4.0% for bDMARDs in 2007, 2011, and 2014, respectively; all p<0.05). The use of bDMARDs was higher among Hispanics compared to Whites (adjusted absolute difference: +7.1%, +7.3%, and +7.5% in 2007, 2011, and 2014, respectively; all p<0.05). Long-term GC use was lower among Hispanics than among Whites only in year 2014 (absolute percentage point difference of -4.2%); no other difference in long-term GC use was identified. Whites were the patients with the highest use of long-term opioids (more than two third in each calendar year). Racial and ethnic differences exists in regards to the treatment of RA among beneficiaries of the SSDI. These findings suggest that this already vulnerable population of patients with RA can also have a racial and ethnic disparity that can contribute to additional disease burden and that should be examined in order to inform future interventions or even inform future policy changes to the SSDI.


Repressible acid phosphatase from yeast efficiently dephosphorylates in vitro some phosphorylated proteins and peptides.
Highly purified repressible acid phosphatase from Saccharomyces cerevisiae very efficiently dephosphorylates 32P-histones and the phosphopeptides Arg-Arg-Ala-Ser-(32P)-Val-Ala and Arg-Arg-Leu-Ser (32P)-Leu-Arg previously phosphorylated by either cAMP-dependent protein kinase or protein kinase-C. The Km values (0.03-1 microM) are very favourable if compared with those calculated for free phosphoaminoacids and p-nitrophenylphosphate which are three to six orders of magnitude higher. While also the phosphopeptide Asp-Ala-Gly-Tyr(32P)-Ala-Arg3-Gly is readily dephosphorylated, other phosphopeptides and phosphoproteins including phosphorylase kinase, phosvitin and casein phosphorylated by both casein kinase 1 and 2 are not appreciably affected by acid phosphatase. It is suggested that yeast repressible acid phosphatase may act in vivo as a phosphoprotein phosphatase.


Development of a Mg/O ReaxFF Potential to describe the Passivation Processes in Magnesium-Ion Batteries.
One of the key challenges preventing the breakthrough of magnesium-ion batteries (MIB) is the formation of a passivating boundary layer at the Mg anode. To describe the initial steps of Mg anode degradation by O2 impurities, a Mg/O ReaxFF (force field for reactive systems) parameter set was developed capable of accurately modeling the bulk, surface, adsorption, and diffusion properties of metallic Mg and the salt MgO. It is shown that O2 immediately dissociates upon first contact with the Mg anode (modeled as Mg(0001), Mg(10 1 ‾ $\bar 1$ 0)A, and Mg(10 1 ‾ $\bar 1$ 1)), heating the surface to several 1000 K. The high temperature assists the further oxidation and forms a rock salt interphase intersected by several grain boundaries. Among the Mg surface terminations, Mg(10 1 ‾ $\bar 1$ 0)A is the most reactive, forming an MgO layer with a thickness of up to 25 Å. The trained force field can be used to model the ongoing reactions in Mg-air batteries but also to study the oxidation of magnesium metal in general.


Femoral replacement for salvage of periprosthetic fracture around a total hip replacement.
A total of 20 patients with a mean age of 72 (range: 36-91) were managed with replacement of the proximal (15) or total (5) femur for salvage of a periprosthetic femoral fracture with bone loss. A mean 12.5 years had elapsed between primary total hip replacement and surgery and the mean follow-up was 48 months (range: 12-116 months). Clinical outcome was assessed using the Toronto Extremity Salvage Score (mean: 68, range: 32-98) and Short Form 36 (SF-36; mean Physical Component Score (PCS): 53, range: 44-62; mean Mental Component Score (MCS): 51, range: 41-64). No prostheses were radiologically loose. There were six major complications; three patients suffered a postoperative dislocation; two patients had persistent deep infection (present preoperatively); and one patient suffered a fracture of their femur distal to the femoral stem of a proximal femoral replacement. Endoprosthetic replacement of the femur is a reasonable salvage option for patients with periprosthetic fracture and bone loss, with good clinical results. It allows immediate weight bearing and does not rely on bony union for success.


Plasma cholesterol response to a change in dietary fat intake: a collaborative twin study.
The rise of plasma cholesterol in response to an increase from 8 to 22.3% in saturated fatty acid of total intake was studied by comparing the concordance of change in pairs of young English and Italian monozygotic (33 pairs) and dizygotic (22 pairs) twins. LDL and total cholesterol rose about 0.6 mmol/l. All methods of analyses showed a marked genetic component influencing total and LDL cholesterol level. However, the genetic component of the increase in LDL and total cholesterol levels was small in Italy and absent in England. These results suggest that the response of plasma cholesterol to this dietary change is largely determined by environmental factors rather than inheritance.


Comparative analysis of superantigen genes in Staphylococcus xylosus and Staphylococcus aureus isolates collected from a single mammary quarter of cows with mastitis.
The purpose of this study was to analyze and compare genes encoding superantigens (SAgs) in Staphylococcus xylosus and Staphylococcus aureus isolates collected simultaneously from milk of the same cows with clinical mastitis. Genes encoding staphylococcal enterotoxins and enterotoxin-like proteins (sea-selu), toxic shock syndrome toxin 1 (tst-1) and exfoliative toxins (eta and etd) were investigated. It was found that among 30 isolates of S. xylosus, 16 (53.3%) harbored from 1 to 10 SAg genes. In total, in 16 SAg positive S. xylosus, 11 different enterotoxin genes were detected: sec, sed, seg, seh, sei, selm, seln, selo, selp, ser, selu and one etd gene encoding exfoliative toxin D. The most prevalent genes were ser, selu, and selo. Among all the positive isolates of S. xylosus, a total of 14 different SAg gene combinations were detected. One combination was repeated in 3 isolates, whereas the rest were detected only once. However, in the case of S. aureus all the 30 isolates harbored the same combination of SAg genes: seg, sei, selm, seln, selo and on the basis of PFGE analysis all belonged to the same clonal type. Also noteworthy was the observation that SAg genes detected in S. aureus have also been found in S. xylosus. The findings of this study further extend previous observations that SAg genes are present not only in S. aureus but also in coagulase-negative staphylococci, including S. xylosus. Therefore, taking into account that the SAg genes are encoded on mobile genetic elements it is possible that these genes can be transferred between different species of coexisting staphylococci.


Zfp503/Nlz2 Is Required for RPE Differentiation and Optic Fissure Closure.
Uveal coloboma is a congenital eye malformation caused by failure of the optic fissure to close in early human development. Despite significant progress in identifying genes whose regulation is important for executing this closure, mutations are detected in a minority of cases using known gene panels, implying additional genetic complexity. We have previously shown knockdown of znf503 (the ortholog of mouse Zfp503) in zebrafish causes coloboma. Here we characterize Zfp503 knockout (KO) mice and evaluate transcriptomic profiling of mutant versus wild-type (WT) retinal pigment epithelium (RPE)/choroid. Zfp503 KO mice were generated by gene targeting using homologous recombination. Embryos were characterized grossly and histologically. Patterns and level of developmentally relevant proteins/genes were examined with immunostaining/in situ hybridization. The transcriptomic profile of E11.5 KO RPE/choroid was compared to that of WT. Zfp503 is dynamically expressed in developing mouse eyes, and loss of its expression results in uveal coloboma. KO embryos exhibit altered mRNA levels and expression patterns of several key transcription factors involved in eye development, including Otx2, Mitf, Pax6, Pax2, Vax1, and Vax2, resulting in a failure to maintain the presumptive RPE, as evidenced by reduced melanin pigmentation and its differentiation into a neural retina-like lineage. Comparison of RNA sequencing data from WT and KO E11.5 embryos demonstrated reduced expression of melanin-related genes and significant overlap with genes known to be dynamically regulated at the optic fissure. These results demonstrate a critical role of Zfp503 in maintaining RPE fate and optic fissure closure.


Effects of autonomic ganglion blockade on fractal and spectral components of blood pressure and heart rate variability in free-moving rats.
Fractal analysis is a promising tool for assessing autonomic influences on heart rate (HR) and blood pressure (BP) variability. The temporal spectrum of scale coefficients, α(t), was recently proposed to describe the cardiovascular fractal dynamics. Aim of our work is to evaluate sympathetic influences on cardiovascular variability analyzing α(t) and spectral powers of HR and BP after ganglionic blockade. BP was recorded in 11 rats before and after autonomic blockade by hexamethonium infusion (HEX). Systolic and diastolic BP, pulse pressure and pulse interval were derived beat-by-beat. Segments longer than 5 min were selected at baseline and HEX to estimate power spectra and α(t). Comparisons were made by paired t-test. HEX reduced all spectral components of systolic and diastolic BP, the reduction being particularly significant around the frequency of Mayer waves; it induced a reduction on α(t) coefficients at t<2s and an increase on coefficients at t>8s. HEX reduced only slower components of pulse interval power spectrum, but decreased significantly faster scale coefficients (t<8s). HEX only marginally affected pulse pressure variability. Results indicate that the sympathetic outflow contributes to BP fractal dynamics with fractional Gaussian noise (α<1) at longer scales and fractional Brownian motion (α>1) at shorter scales. Ganglionic blockade also removes a fractional Brownian motion component at shorter scales from HR dynamics. Results may be explained by the characteristic time constants between sympathetic efferent activity and cardiovascular effectors. Therefore fractal analysis may complete spectral analysis with information on the correlation structure of the data.


Dietary supplementation with omega-3 polyunsaturated fatty acids in patients with stable coronary heart disease. Effects on indices of platelet and neutrophil function and exercise performance.
It has been suggested that omega-3 polyunsaturated fatty acids (PUFAs) may alter the course of coronary artery disease by influencing platelet and neutrophil function, arachidonic acid metabolism, and circulating lipid concentrations. To examine this hypothesis, placebo or omega-3 PUFAs as Max-EPA (equivalent to 3.2 g of eicosapentaenoic acid and 2.2 g of docosahexaenoic acid daily) was administered to eight patients with stable coronary artery disease and positive exercise stress test results in a randomized, double-blind, crossover fashion over a 12-week period. With Max-EPA administration, platelet aggregation threshold to epinephrine was increased in only two patients, but neutrophil aggregation and chemotaxic functions decreased consistently (both p less than or equal to 0.01 compared with preceding placebo phase) in all eight. Serum and platelet-rich plasma thromboxane B2 concentrations decreased 40 percent and 28 percent, respectively (both p less than or equal to 0.05). Neutrophil leukotriene B4 formation decreased 23 percent (p less than or equal to 0.01) and synthesis of leukotriene B5 became apparent in all subjects. Serum triglyceride concentrations fell 52 percent (p less than or equal to 0.05) without significant change in total cholesterol, high-density lipoprotein-cholesterol, or low-density lipoprotein-cholesterol concentrations. Systolic blood pressure and the double product (heart rate X systolic blood pressure) were lower (p less than or equal to 0.05) at the end of the Max-EPA phase than in the preceding placebo phase. Heart rate, systolic blood pressure, and the double product were also lower (p less than or equal to 0.05) at three as well as at six minutes of an exercise stress test, indicating a significant reduction in myocardial oxygen demand. Despite these alterations in platelet and neutrophil function, arachidonic acid metabolism, serum triglyceride concentrations, and myocardial oxygen demand, there were no significant changes in subjective parameters of coronary artery disease during the Max-EPA phase (angina frequency 3.7 versus 2.8 episodes per week, nitroglycerin consumption 3.0 versus 1.9 tablets per week, both p = NS). Similarly, exercise times to ST-segment depression (6.5 versus 4.1 minutes) and to onset of angina (5.4 versus 5.0 minutes) were not altered by administration of Max-EPA. Thus, short-term dietary supplementation with omega-3 PUFAs to patients with stable coronary artery disease does not appear to alter subjective or objective parameters of myocardial ischemia.


Posterior mediastinal teratoma involving the esophagus.
Intrathoracic teratomas are difficult to diagnose on chest radiographs if they are noncalcified and located in an atypical site. We report an unusual case of posterior mediastinal teratoma that involved the esophageal wall. Features noted on computed tomography (CT) of the chest and barium examination of the esophagus are herein presented.


Anesthesia machine as a cause of intraoperative "code red" in the labor and delivery suite.
Fire is a rare but potentially disastrous operating room misadventure. I herein describe the first reported case of a fire in the labor and delivery suite, which also happens to be the first case of a fire caused by malfunctioning anesthesia machine.


In vivo purging and relapse prevention following ASCT.
The combination of high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative therapy for patients with relapsed chemosensitive non-Hodgkin's lymphoma (NHL) and is increasingly being considered as a first-line treatment for NHL patients with poor prognosis or poor outcomes from chemotherapy. However, there is a degree of relapse following the latter which is associated with high levels of tumour cell contamination of the stem cells and/or the presence of residual malignant cells in the host following chemotherapy. Reducing the rate of relapse can be achieved by pre-transplant purging of the stem cell graft followed by post-transplant maintenance to minimise residual disease. Various methods of in vitro purging have been shown to reduce, but not eliminate, the level of stem cell contamination and invariably result in a reduced harvest. To date, this has been reflected in disappointing outcomes for the patient. In contrast, in vivo purging with rituximab during the process of stem cell mobilisation and collection does not adversely affect the yield or function of stem cells and shows a significant improvement in the level of tumour cell contamination as measured by bcl-2 clearance. The relapse potential from residual malignant cells in the host can be addressed by a programme of post-transplant rituximab maintenance therapy. In one study 17 patients with follicular lymphoma who underwent ASCT with in vivo rituximab-purged stem cells, followed by rituximab maintenance, have all remained in complete response at a median follow-up of 12.4 months. The optimum in vivo rituximab purging protocol and the precise effect in terms of overall and disease-free survival are currently being evaluated but appear to present an attractive first-line alternative for NHL patients with poor prognosis or poor outcomes following chemotherapy.


An evidence of 'post-seizure excitation' in feline-kindled seizures.
We assessed the post-seizure effects on the seizure threshold and the seizure duration using low-frequency kindling technique. The number of stimulating pulses required for a triggering of epileptic afterdischarge (pulse-number threshold; PNT) was used for the indicator of seizure threshold. PNT increased significantly at 2 and 4 h inter-stimulation intervals, whereas it decreased significantly with an increase of seizure duration at 16 and 24 h intervals. It appears from these data that a post-seizure excitation occurs after a post-seizure inhibition.


Randomized, controlled trial of breath therapy for patients with chronic low-back pain.
Patients suffering from chronic low back pain (cLBP) are often unsatisfied with conventional medical care and seek alternative therapies. Many mind-body techniques are said to help patients with low back pain by enhancing body awareness, which includes proprioception deficit in cLBP, but have not been rigorously studied in cLBP. Breath therapy is a western mind-body therapy integrating body awareness, breathing, meditation, and movement. Preliminary data suggest benefits from breath therapy for proprioception and low back pain. To assess the effect of breath therapy on cLBP. Randomized, controlled trial. Academic medical center. Thirty-six patients with cLBP. Six to eight weeks (12 sessions) of breath therapy versus physical therapy. Pain by visual analog scale (VAS), function by Roland Scale, overall health by Short Form 36 (SF-36) at baseline, six to eight weeks, and six months. Balance as a potential surrogate for proprioception and body-awareness measured at the beginning and end of treatment. Pre- to post-intervention, patients in both groups improved in pain (VAS: -2.7 with breath therapy, -2.4 with physical therapy; SF-36: +14.9 with breath therapy and +21.0 with physical therapy). Breath therapy recipients improved in function (Roland: -4.8) and in the physical and emotional role (SF-36: +15.5 and 14.3). Physical therapy recipients improved in vitality (SF-36: +15.0). Average improvements were not different between groups. At six to eight weeks, results showed a trend favoring breath therapy; at six-months, a trend favoring physical therapy. Balance measures showed no improvements and no correlations with other outcomes. Patients suffering from cLBP improved significantly with breath therapy. Changes in standard low back pain measures of pain and disability were comparable to those resulting from high-quality, extended physical therapy. Breath therapy was safe. Qualitative data suggested improved coping skills and new insight into the effect of stress on the body as a result of breath therapy. Balance measures did not seem to be valid measures of clinical change in patients' cLBP.


Molecular characterization of the NCoA-1-STAT 6 interaction.
Many protein-protein interactions involved in cell signalling, cell adhesion and regulation of transcription are mediated by short alpha-helical recognition motifs with the sequence Leu-Xaa-Xaa-Leu-Leu (LXXLL, where Xaa is any amino acid). Originally observed in cofactors that interact with hormone-activated nuclear receptors, LXXLL motifs are now known to occur in many transcription factors, including the STAT family, which transmit signals from activated cytokine receptors at the cell surface to target genes in the nucleus. STAT 6 becomes activated in response to IL-4 and IL-13, which regulate immune and anti-inflammatory responses. Structural studies have revealed how an LXXLL motif located in 2.5 turns of an alpha-helical peptide derived from STAT 6 provide contacts through the leucine side chains to the coactivator of transcription, NCoA-1. However, since many protein-protein interactions are mediated by LXXLL motifs, it is important to understand how specificity is achieved in this and other signalling pathways. Here, we show that energetically important contacts between STAT 6 and NCoA-1 are made in residues that flank the LXXLL motif, including the underlined residues in the sequence LLPPTEQDLTKLL. We also demonstrate how the affinity for NCoA-1 of peptides derived from this region of STAT 6 can be significantly improved by optimising knobs-into-holes contacts on the surface of the protein. The results provide important new insights into the origins of binding specificity, and might be of practical value in the design of novel small-molecule inhibitors of this important protein-protein interaction.


Therapeutic ultrasound plus pulsed electromagnetic field improves recovery from peripheral arterial disease in hypertension.
The objective of this investigation was to evaluate the therapy effect of combined therapeutic ultrasound (TUS) treatment and pulsed electromagnetic field (PEMF) therapy on angiogenesis in hypertension-related hindlimb ischemia. After subjecting excision of the left femoral artery, spontaneously hypertensive rats (SHRs) were randomly distributed to one of four groups: SHR; TUS treated SHR (SHR-TUS); PEMF treated SHR (PEMF-TUS); and TUS plus PEMF treated SHR (SHR-TUS-PEMF). Wistar-Kyoto rats (WKYs) with femoral artery excision were regarded as a control group. At day 14 after surgery, the TUS plus PEMF united administration had the greatest blood perfusion accompanied by elevated capillary density and the lowest TUNEL index. Interestingly, the united administration up-regulated the angiogenic factors expression of phosphorylated Akt (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS), vascular endothelial growth factor (VEGF), anti-apoptotic protein of Bcl-2 and down-regulated pro-apoptotic protein levels of Bax and Cleaved caspase-3 in vivo. Our results demonstrated that the united administration could significantly rescue hypertension-related inhibition of ischemia-induced neovascularization partly by promoting angiogenesis and inhibiting apoptosis.


Protective effects of adenosine in the reversibly injured heart.
There is substantial evidence that the nucleoside adenosine reduces postischemic ventricular dysfunction (ie, myocardial stunning). Studies performed in our laboratory have attempted to address the mechanism of adenosine-mediated protection of the reversibly injured heart. Experiments were performed in isolated perfused rat and rabbit hearts and in in situ canine and porcine preparations. The role of adenosine A1 receptors was assessed by using adenosine A1 receptor agonists and antagonists, and by measuring interstitial fluid purine levels with the cardiac microdialysis technique. In isolated perfused hearts, treatment immediately before ischemia with adenosine and adenosine A1 receptor analogues significantly improved postischemic ventricular function, effects that were blocked by a selective adenosine A1 receptor antagonist. In in situ canine and porcine preparations, pretreatment with adenosine and an adenosine deaminase inhibitor increased preischemic interstitial fluid adenosine levels and attenuated regional myocardial stunning. Adenosine treatment was also associated with improved myocardial phosphorylation potential in isolated guinea pig hearts and in the in situ porcine preparation. These results suggest that adenosine-induced attenuation of myocardial stunning is mediated via adenosine A1 receptor activation and enhancement of postischemic myocardial phosphorylation potential.


Tetra-methyl-ammonium (Z)-N'-cyano-carbamimidate.
In the structure of the tetra-methyl ammonium salt of cyano-urea, C4H12N+·C2H2N3O-, the N-C and O-C bond distances in the cyano and keto groups are in the normal range for such a moieties at 1.1641 (18) and 1.2550 (16) Å. However, the bonds about the central C and N atoms are much shorter than would be expected for single bonds and indicate that there is considerable electron delocalization in the anion as was also found in the silver salt. The NH2 group is coplanar with the central N2CO core, in contrast with the nitrile group where the dihedral angle between the N-C-N and N2CO planes is 36.5 (3)°. The packing of the cations and anions in the unit cell involves N-H⋯O hydrogen bonds between anions characterized by an R 2 2(8) motif, as well as N-H⋯O hydrogen bonds between anions and C-H⋯O inter-actions between both cations and anions, forming an R 3 3(14) pattern.


Myasthenic Crisis After Recurrent COVID-19 Infection.
A patient with myasthenia gravis who survived 2 COVID-19 infections required plasmapheresis to recover from an acute crisis.


CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma.
CXCR2 has been suggested to have both tumor-promoting and tumor-suppressive properties. Here we show that CXCR2 signaling is upregulated in human pancreatic cancer, predominantly in neutrophil/myeloid-derived suppressor cells, but rarely in tumor cells. Genetic ablation or inhibition of CXCR2 abrogated metastasis, but only inhibition slowed tumorigenesis. Depletion of neutrophils/myeloid-derived suppressor cells also suppressed metastasis suggesting a key role for CXCR2 in establishing and maintaining the metastatic niche. Importantly, loss or inhibition of CXCR2 improved T cell entry, and combined inhibition of CXCR2 and PD1 in mice with established disease significantly extended survival. We show that CXCR2 signaling in the myeloid compartment can promote pancreatic tumorigenesis and is required for pancreatic cancer metastasis, making it an excellent therapeutic target.


[Medical certificates for intentional wounds and blows in medico-legal practice in Dakar].
Drawing up the medical certificate is a crucial step in the judicial process. This judicial document should be drafted during a medical legal consultation. This study aims to evaluate the quality of medical certificates in a medico-judicial consultation and to study interpretative criteria of medical certificate validity. We conducted a retrospective study of patient's victims of intentional wounds and blows receiving a medico-judicial consultation at the Grand Yoff General Hospital, from April 2012 to February 2015. The whole of medical certificates were recorded on a survey form analyzed by Epi Info Version 6.04. The whole of the 249 certificates studied was printed in legible and understandable "Arial police 12". All the studied medical certificates included complete identification of the physician and the victim. The date and the time of aggression were written in 248 certificates (99.6%). The type of abuse suffered was specified on the whole of the 249 certificates: 164 brawls (65.9%), 64 unilateral aggressions (25.7%). The precise description and nature of the lesions was written in 246 certificates. The site of the lesions was established based on fixed anatomical landmarks in the various body plans. Medico-judicial consultation, coordinated by the forensic physician, helped to significantly improve the quality of the documents issued. The dissemination of these drafting practices and of the practices concerning the issuing of certificates is essential in particular in the regional hospital as part of an ongoing training or postgraduate training.


Silver staining of human aqueous humor proteins resolved by gel electrophoresis.
The detection of aqueous humor proteins resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was achieved using an ultrasensitive silver staining technique. This procedure permitted the detection of more than 35 different protein bands in human aqueous humor on a one-dimensional gel. Most of the stained proteins had an apparent molecular weight greater than 45,000 daltons.


Development of an emergency medicine pharmacy intensity score tool.
Emergency medicine pharmacists (EMPs) have been demonstrated to have a positive impact on patient outcomes in a variety of clinical scenarios in the emergency department (ED), yet their distribution across the nation is suboptimal. An emergency medicine pharmacy intensity score tool (EMPIST) would not only facilitate the quantification of EMP staffing needs and ideal resource deployment times, but would also allow practitioners to triage patient care activities. The purpose of this investigation was to develop an EMPIST and evaluate its relationship to EMP activities. This was a multicenter, prospective, observational analysis of an EMPIST developed by practicing EMPs. EMPs prospectively documented their clinical activities during usual care for patients in their ED. Spearman's rank-order correlation was used to determine any correlation between the EMPIST and pharmacist activities. In total, 970 EMP activities and 584 EMPIST items were documented in 352 patients by 7 EMPs across 7 different EDs. The most commonly documented EMP interventions performed were bedside monitoring (12.7%), initiation of nonantimicrobial therapy (12.6%), and antimicrobial therapy initiation and streamlining (10.6%). The total EMPIST was found to significantly correlate with EMP activities, and this correlation was consistent across both "diagnostic/presentation" and "medication" items (P < 0.001 for all comparisons). The EMPIST significantly correlated with EMP activities, with consistent correlation across all subgroups. Its utilization has the potential to enhance bedside clinical practice and optimize the deployment of limited EMP services. Additional investigations are needed to examine the validity of this tool and identify any relationship it may have to patient outcomes.


A systematic chart review of the naturalistic course and treatment of early-onset bipolar disorder in a child and adolescent psychiatry center.
Studies on the naturalistic course of early-onset bipolar disorder are few and studies evaluating the efficacy of pharmacotherapy consist largely of open trials of thymoleptics and neuroleptics on small samples. The current study was undertaken to map the course of the disorder and the prevailing prescribing practice in early-onset bipolar disorder at a child and adolescent psychiatry center in India. A chart review of 139 children and adolescents (<16 years) with a DSM-IV diagnosis of bipolar disorder-mania was performed and the baseline demographic and clinical characteristics, episode characteristics, and treatment and follow-up details were collected and the data analyzed. The index episode remitted in all 133 (96%) subjects for whom the information was available. One hundred twenty-five (90%) subjects received thymoleptics for the index episode, of which lithium was used in 85%. Valproate was the next most commonly used thymoleptic (18%). Eighteen (13%) subjects received combination thymoleptics. Sixty-eight percent received neuroleptics either alone or as adjuncts in the acute phase. During the follow-up period, which ranged from 3 to 56 months (mean +/- SD, 15 +/- 14), 35% of subjects relapsed, 89% within the first 2 years. Twenty-eight percent of subjects relapsed despite being on apparently adequate doses of lithium. The limitations of the study are that it is retrospective in nature, and that structured diagnostic tools and rating scales were not used. We conclude that lithium is the most commonly used thymoleptic in early-onset bipolar disorder. Lithium alone or in combination with neuroleptics appears to have good efficacy in the acute phase of the disorder. The majority of relapses occurred in the first 2 years and the efficacy of currently used thymoleptics in prophylaxis is uncertain.


Isolation and characterization of the sulfated glycosaminoglycans of the vitreous body.
Ester sulfate containing glycosaminoglycans comprising approx. 3% of the total glycosaminoglycan content, have been isolated from protease-digested bovine vitreous body by stepwise fractionation on AG-1X2(Cl-) and gel filtration on Bio-Gel P-300. Two heparan sulfate and two chondroitin-4-sulfate fractions were isolated in nearly pure form. The heparan sulfate fractions were undersulfated and contained the same relative proportions of N- and O-sulfate (1:2), although the total sulfate content differed by approx. 100%. No chondroitin-6-sulfate was present in the isolates, based on evidence obtained from chondroitin ABC lyase experiments.


The interaction between liver cirrhosis, infection by Streptococcus bovis, and colon cancer.
Whether cirrhotic patients with Streptococcus bovis bacteremia have an increased risk of colorectal neoplasm is uncertain. A multicentric retrospective cohort study was conducted investigating associations between S. bovis biotype and species, cirrhosis, and colorectal neoplasm. Out of 779 patients with S. bovis bacteremia, 69 (8.7%) had cirrhosis. No differences were found in the prevalence of colorectal neoplasm between cirrhotic and non-cirrhotic patients undergoing colonoscopy. Among cirrhotic patients, prevalence of colorectal neoplasms was higher in S. bovis biotype I (S. gallolyticus) bacteremia (80%) than in S. bovis biotype II (33.3%; p < 0.007). In conclusion, risk of colorectal neoplasm is high among cirrhotic patients with S. gallolyticus bacteremia.


Visual results after keratoplasty in patients with posterior chamber intraocular lenses.
We performed penetrating keratoplasty in 20 consecutive patients who had posterior chamber intraocular lenses and who developed pseudophakic bullous keratopathy. All patients received 8.0-mm grafts placed in 7.5-mm recipient beds. None of the intraocular lenses were removed. Final visual acuity was 20/40 or better in eight (40%) and 20/80 or better in 15 (75%) of the patients. Senile macular degeneration (one case), corneal graft rejection (two cases), and wound infection (one case) contributed to poor visual results in the remaining patients.


Corrigendum to 'Disseminated mucormycosis in a paediatric patient: Lictheimia corymbifera successfully treated with combination antifungal therapy' [Medical Mycology Case Reports (2014) 18-21].
[This corrects the article DOI: 10.1016/j.mmcr.2014.08.002.].


Inhibition of mRNA maturation in trypanosomes causes the formation of novel foci at the nuclear periphery containing cytoplasmic regulators of mRNA fate.
Maturation of all cytoplasmic mRNAs in trypanosomes involves trans-splicing of a short exon at the 5' end. Inhibition of trans-splicing results in an accumulation of partially processed oligocistronic mRNAs. Here, we show that the accumulation of newly synthesised partially processed mRNAs results in the formation of foci around the periphery of the nucleus. These nuclear periphery granules (NPGs) contain the full complement of P-body proteins identified in trypanosomes to date, as well as poly(A)-binding protein 2 and the trypanosome homologue of the RNA helicase VASA. NPGs resemble perinuclear germ granules from metazoa more than P-bodies because they: (1) are localised around the nuclear periphery; (2) are dependent on active transcription; (3) are not dissipated by cycloheximide; (4) contain VASA; and (5) depend on nuclear integrity. In addition, NPGs can be induced in cells depleted of the P-body core component SCD6. The description of NPGs in trypanosomes provides evidence that there is a perinuclear compartment that can determine the fate of newly transcribed mRNAs and that germ granules could be a specialised derivative.


The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression.
The innate immune system is dysregulated in depression; however, less is known about the longitudinal associations of depression and inflammatory biomarkers. We investigated the prospective associations of depression and inflammatory biomarkers [interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-α), and C-reactive protein (CRP)] in community samples, both unadjusted and adjusted for covariates. The review, registered with PROSPERO, searched for published and unpublished studies via MEDLINE/PsycINFO/PsycARTICLES/EMBASE/Proquest Dissertation. Standardized Fisher transformations of the correlation/beta coefficients, both unadjusted and adjusted for covariates, were extracted from studies examining the prospective associations of depression and inflammatory biomarkers. Systematic review conducted in January, 2019 included 38 studies representing 58,256 participants, with up to 27 studies included in random-effects meta-analysis. Higher CRP/IL-6 were associated with future depressive symptoms, and higher depressive symptoms were associated with higher future CRP/IL-6 in both unadjusted and adjusted analyses - this is the first meta-analysis reporting an adjusted association of IL-6 with future depression. The adjusted prospective associations of depression with CRP/CRP with depression were substantially attenuated and small in magnitude. No significant associations were observed for TNF-α. No conclusive results were observed in studies of clinical depression. Meta-regression indicated that the association of CRP and future depression was larger in older samples and in studies not controlling for possible infection. Small, prospective associations of depression and inflammatory biomarkers are observed in both directions, particularly for IL-6; however, the strength and importance of this relationship is likely obscured by the heterogeneity in depression and profound study/methodological differences. Implications for future studies are discussed.


Eimeria tenella: effects of immunity on sporozoites within the lumen of the small intestine.
The effect of immunity on the numbers of sporozoites of Eimeria tenella recoverable from the lumen of the small intestine 1 hr after an oral challenge inoculum of oocysts was examined. The experiments were carried out in chickens which had been given an immunizing inoculum of oocysts 9 or 18 days earlier, and the results were compared with those obtained in a control, unprimed, but similarly challenged, group. Similar numbers of "challenge" sporozoites were found in the intestinal washes of control and 18 day primed chickens but there were fewer in the 9 day primed groups. The titers of antisporozoite IgA antibodies (measured by indirect fluorescence) were higher in the gall bladder bile of the 9 day primed groups but resistance to reinfection (measured by the output of oocysts in the feces after challenge with oocysts orally or with sporozoites intracecally) was greater in the 18 day primed group. Although fewer in number, the challenge sporozoites recovered from the intestinal washes of 9 day primed chickens appeared to be morphologically normal when examined by light microscopy. Also, they were as infective as sporozoites recovered from unprimed control, or 18 day primed, groups when injected intracecally into naive chickens. The findings indicate that, whereas reduction of the number of sporozoites of E. tenella in the lumen of the small intestine (presumably caused by the action of secreted antibodies) can be a means of reducing the effective challenge inoculum, this mechanism does not play a major role in the expression of immunity.


Severe Respiratory Syncytial Virus Infection in Hospitalized Children.
Lower respiratory tract infections (LRTI) are one of the most common causes of death worldwide. Respiratory syncytial virus (RSV) is a leading cause of LRTI in children. Despite of its epidemiological importance, there is limited information regarding the impact of this virus in Latin America. We carried out a prospective study to establish the frequency and characteristics of RSV infections in hospitalized Mexican children. 1,252 children hospitalized between November, 2012 and December, 2015 because of LRTI were included in the study. A respiratory sample was obtained for RSV detection by RT-PCR and information regarding clinical presentation, hospital course, and outcome was recorded. RSV was detected in 43.7% of children admitted with LRTI, in 43.3% of those admitted to the intensive care unit (ICU), and in 36.4% of those who died. Infants with RSV infection were younger, were diagnosed with bronchiolitis more frequently, and were less likely to have underlying disorders than those with RSV-negative LRTI. Among RSV-positive infants, admission to the ICU was associated with the presence of underlying conditions, pneumonia diagnosis, and young age. Four (0.73%) of the 547 infants with RSV infection died; death was more common in those with underlying disorders than previously healthy infants (3.8 vs. 0.2%, respectively; p = 0.02). RSV contributes to a large proportion of LRTI hospital admissions. Most children admitted with RSV infection do not have underlying conditions. However, severe infection requiring ICU admission and death are more common in those with underlying disorders.


Impact of the COVID-19 pandemic upon a universal electronic consultation program (e-consultation) between general practitioners and cardiologists.
Virtual healthcare models, usually between healthcare professionals and patients, have developed strongly during the coronavirus disease 2019 (COVID-19) pandemic, but there are no data corresponding to models between clinicians. An analysis was made of the impact of the COVID-19 pandemic upon the activity and health outcomes of the universal e-consultation program for patient referrals between primary care physicians and the Cardiology Department in our healthcare area. Patients with at least one e-consultation between 2018 and 2021 were selected. We analyzed the impact of the COVID-19 pandemic upon activity and waiting time for care, hospitalizations and mortality, taking as reference the consultations carried out during 2018. A total of 25,121 patients were analyzed. Logistic regression analysis showed a shorter delay in care and resolution of the e-consultation without the need for face-to-face care to be associated to a better prognosis. The COVID-19 pandemic periods (2019-2020 and 2020-2021) were not associated to poorer health outcomes compared to 2018. The results of our study show a significant reduction in e-consultation referrals during the first year of the COVID-19 pandemic, with a subsequent recovery in the demand for care, and without the pandemic periods being associated to poorer outcomes. The reduction in time elapsed for resolving the e-consultations and no need for face-to-face visits were associated to improved outcomes.


Application of cicatricial contracture release principles in muscular torticollis treatment.
Numerous surgical approaches for muscular torticollis are not effective enough to completely release the contracture and prevent further development of craniofacial asymmetry. Cosmetically unacceptable scars on the neck and compulsory functional exercises after surgery were also common problems. We applied the therapeutic principle of scar contracture to the surgical treatment of muscular torticollis. Surgical incision determination and the postoperative protocol were considerably improved. Satisfactory results were obtained. According to the therapeutic principle of scar contracture, complete release of the contracted muscles and peripheral streak fascia and release or partial resection of peripheral normal tissues such as the scalenus anterior, anterior trapezius border, platysma, and partial carotid sheath are required to release all the affected contracted and tightened tissues. We chose to incise underneath the affected side of the clavicular border. We obtained a tension-free closure of the incision through an advanced skin flap of the inferior incision sutured on the clavicular fascia. Maximum head and neck stretch to the unaffected side of the shoulder when the patient lied down gave the affected side lateral decubitus position after surgery. Satisfactory results were obtained and no complications were identified for all of the 104 patients. The development of craniofacial asymmetry and progressive deformities was prevented. The incision scar appeared linear in the pit above or below the clavicle border and was relatively inconspicuous. The application of the therapeutic principle of scar contracture to the surgical treatment of muscular torticollis was successful.


Sleep Deficiency in the Elderly.
With aging, there are normative changes to sleep physiology and circadian rhythmicity that may predispose older adults to sleep deficiency, whereas many health-related and psychosocial/behavioral factors may precipitate sleep deficiency. In this article, we describe age-related changes to sleep and describe how the health-related and psychosocial/behavioral factors typical of aging may converge in older adults to increase the risk for sleep deficiency. Next, we review the consequences of sleep deficiency in older adults, focusing specifically on important age-related outcomes, including mortality, cognition, depression, and physical function. Finally, we review treatments for sleep deficiency, highlighting safe and effective nonpharmacologic interventions.


An unusual cause of visual impairment in tuberculous meningitis.
Impairment of vision is a devastating complication of tuberculous meningitis which may occur as a result of increased intracranial pressure, compression over the visual pathways or vasculitis. We herein present occurrence of neuroretinitis in a 35-year-old lady presenting with low grade fever and headache for one month, and associated with diminution of vision from 3 weeks. She was diagnosed as a case of definite tuberculous meningitis and initiated on anti-tuberculous treatment as per WHO guidelines with supplemental corticosteroids. Marked improvement in vision was observed and at 3 months of follow-up the patient was asymptomatic. Direct ophthalmoscopy, visual field analysis, fluorescein angiography, optical coherence tomography and magnetic resonance imaging of the brain were done to document the ophthalmological findings. Neuroretinitis, being an unusual cause of visual impairment in tuberculous meningitis, must be considered in patients without any evidence of raised intracranial pressure or compression, and with normal fluorescein angiography. We suggest that neuroretinitis may be added to list of causes of visual impairment in patients with tuberculous meningitis.


Fasciola hepatica: carbohydrate metabolism of the adult.
Glycogen (or exogenous glucose) was the only energy source utilized by adult Fasciola hepatica under a number of different incubation conditions. When exogenous glucose was present in the incubation medium, significant amounts of lactate were excreted. Anaerobically, in the presence of glucose, lactate accounted for 20% of the total end products measured. In the absence of glucose, organic acid production accounted for approximately 60% of glycogen carbon utilized; this value was reduced to 40% in the presence of exogenous glucose. There was no appreciable Pasteur effect.


Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects.
The T cell receptor (TCR) signaling pathway is an ensemble of numerous proteins that are crucial for an adequate immune response. Disruption of any protein involved in this pathway leads to severe immunodeficiency and unfavorable clinical outcomes. Here, we describe an infant with severe immunodeficiency who was found to have novel biallelic mutations in SLP76. SLP76 is a key protein involved in TCR signaling and in other hematopoietic pathways. Previous studies of this protein were performed using Jurkat-derived human leukemic T cell lines and SLP76-deficient mice. Our current study links this gene, for the first time, to a human immunodeficiency characterized by early-onset life-threatening infections, combined T and B cell immunodeficiency, severe neutrophil defects, and impaired platelet aggregation. Hereby, we characterized aspects of the patient's immune phenotype, modeled them with an SLP76-deficient Jurkat-derived T cell line, and rescued some consequences using ectopic expression of wild-type SLP76. Understanding human diseases due to SLP76 deficiency is helpful in explaining the mixed T cell and neutrophil defects, providing a guide for exploring human SLP76 biology.


Evaluating the reproductive ability of breeding rams in North-Eastern Spain using clinical examination of the body and external genitalia.
Predicting the ability of rams to detect, mate and fertilise ewes in oestrus accurately is certainly difficult; however, tests based on clinical examinations have been performed to assess the overall potential capacity of rams to serve and impregnate ewes. Clinical examinations for breeding soundness evaluation were carried out in 897 Rasa Aragonesa (RA) rams from 35 flocks in North-Eastern (NE) Spain. Clinical examinations of head, trunk, limbs and genitals were performed in each ram. Blood samples were collected for a serological study of Brucella ovis. The sheep owners were surveyed regarding the characteristics of the flock, rams' health history and the management of rams. The clinical alterations found were classified according to severity (mild or severe). Rams were classified as suitable (without lesions or with only mild lesions) or unsuitable (with severe lesions) for breeding depending on the results of the clinical examinations. The results showed that 60.6 % of rams presented some type of alteration (mild: 43.3 %; severe: 17.3 %) in various body parts (genitalia: 31.6 %; head and trunk: 37.2 %; limbs: 15.5 %), and that 16.7 % of rams were classified as unsuitable breeders. The most common genital alterations were ulcerative posthitis (18.7 %) followed by testicular lesions (5.3 %). The highest prevalence of unsuitable breeders was found in the category of adult and aged rams (13.8 % and 37.4 %, respectively) and in the category of emaciated rams (33.3 %). All rams examined were seronegative to Brucella ovis. The mean percentage of rams in flocks was 2.8 % (min: 1.6 %; max: 4.6 %); nevertheless, this percentage dropped to 2.5 % (min: 1.4 %; max: 3.7 %) and 2.1 % (min: 0.3 %; max: 3.5 %) when only suitable or effective (suitable mature) rams were considered. Thus, it is concluded that there are fewer effective rams in farms than farmers realise. Frequent clinical examination of males is recommended in order to identify potentially infertile rams.


Expression of apurinic/apyrimidinic endonuclease-1 (APE-1) in H. pylori-associated gastritis, gastric adenoma, and gastric cancer.
Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme in DNA base excision repair (BER), linked to cancer chemosensitivity. However, little is known about the localization of APE-1 in Helicobacter pylori-infected gastric mucosa or its role in the development of gastric cancer. To investigate the role of APE-1 in the development of gastric cancer, we examined APE-1 expression and localization in cultured cells and gastric biopsies from patients with H. pylori-infected gastritis or gastric adenoma, and from surgically resected gastric cancer. APE-1 mRNA and protein expression were determined in H. pylori (CagA+) water-extract protein (HPWEP)-stimulated MKN-28 cells, gastric adenocarcinoma cell-line (AGS) cells, and human peripheral macrophages by real-time polymerase chain reaction and Western blot analysis. APE-1 expression and 8-OHdG as a measure of oxidative DNA damage were evaluated by immunostaining. Localization of APE-1 and IkappaBalpha phosphorylation in gastric adenoma and gastric cancer tissues were evaluated by single- and double-label immunohistochemistry. In studies in vitro, HPWEP-stimulation significantly increased APE-1 mRNA expression levels in both MKN-28 cells and human peripheral macrophages. Hypo/reoxygenation treatment significantly increased APE-1 protein expression in HPWEP-stimulated MKN-28 cells. HPWEP stimulation significantly increased both APE-1 expression and IkappaBalpha phosphorylation levels in MKN-28 and AGS cells. In human tissues, APE-1 expression in H. pylori-infected gastritis without goblet cell metaplasia was significantly increased as compared to that in tissues from uninfected subjects. Eradication therapy significantly reduced both APE-1 and 8-OHdG expression levels in the gastric mucosa. APE-1 expression was mainly localized in epithelial cells within gastric adenoma and in mesenchymal cells of gastric cancer tissues. APE-1 expression in gastric cancer tissues was significantly reduced compared to that in H. pylori-infected gastric adenoma, while 8-OHdG index and IkappaBalpha phosphorylation levels did not differ between these two neoplastic tissue types. Co-localization of APE-1 and IkappaBalpha phosphorylation was observed not in gastric cancer cells but in gastric adenoma cells. H. pylori infection is associated with increased APE-1 expression in human cell lines and in gastric tissues from subjects with gastritis and gastric adenomas. The observed distinct expression patterns of APE-1 and 8-OHdG in gastric adenoma and gastric cancer tissues may provide insight into the progression of these conditions and warrants further investigation.


Mechanisms of macrophage-mediated tumor cell killing: a comparative analysis of the roles of reactive nitrogen intermediates and tumor necrosis factor.
The roles of tumor necrosis factor (TNF alpha) and reactive nitrogen intermediates (RNI) as effectors of macrophage-mediated tumor cell killing were investigated in a variety of tumor cell lines. Three TNF alpha-sensitive tumor targets were also susceptible to resting bone-marrow-derived mononuclear phagocytes (BMMP). This macrophage lytic activity was markedly diminished or even abolished by anti-TNF alpha, indicating that TNF alpha is the major effector of macrophage-mediated killing of these targets. The other 21 tumor cell lines examined were resistant to TNF alpha but, in their large majority, were more or less susceptible to killing by interferon gamma (IFN gamma)- and Corynebacterium parvum (CP)-activated BMMP. Among the various analogues of L-arginine used to assess the role of L-arginine-derived RNI as mediators of macrophage tumoricidal activity, NG-monomethyl-L-arginine (NMMA) was most efficient in suppressing RNI secretion by activated macrophages. In some macrophage tumor-cell combinations, NMMA inhibited both the generation of RNI and the expression of tumoricidal activity in a dose-dependent manner, suggesting a central role for RNI as effectors. In other combinations, NMMA in concentrations that abolished secretion of RNI either affected tumor-cell killing only after its induction by IFN gamma, or not at all. The findings not only support the thesis that macrophages posses various means of coping with tumor cells but also suggest that the mechanism becoming operative is determined predominantly by the pathway of macrophage activation and the properties of the tumor-cell type.


Esophageal adenocarcinoma following Heller myotomy for achalasia.
We describe a patient who developed an esophageal adenocarcinoma 25 years after esophagomyotomy for achalasia. The tumor arose in a Barrett's esophagus, suggesting gastroesophageal acid reflux following the Heller procedure.


[Blood pressure regulation in neurosurgical interventions in the lumbar area in the seated patient].
It has been proved studies of the physiology of the circulatory system that a sufficient regulatory mechanism is present during intervertebral disk operations on the sitting patient. So this positioning variant can be well recommended from an anaesthesiological point of view. Patients without a sufficient blood pressure regulation should be excepted from this positioning variant.


Myocardial infarction caused by blunt chest injury: possible mechanisms involved--case reports.
Two cases are reported in which blunt chest trauma caused myocardial infarction. Coronary angiography revealed apical aneurysms in both patients with normal coronary arteries in the first and total occlusion of left anterior descending artery in the other. The main possible mechanisms of myocardial infarction after blunt chest trauma are discussed.


Bile canalicular barrier function and expression of tight-junctional molecules in rat hepatocytes during common bile duct ligation.
Tight junctions of hepatocytes form the intercellular barrier between the blood circulation and bile flow. We focused on early stages of common bile duct ligation to observe changes in tight junctions without the irreversible changes seen after lengthy ligation. Common bile ducts of 12-week-old male rats were ligated for 6 h because, at this time point, no histological changes were observed. Serum bilirubin and bile acid levels began to increase 3 h after ligation and were restored to the control level immediately after surgical removal of the ligation. To examine the barrier of hapatocytes, horseradish peroxidase was injected via the femoral vein, and bile was collected for the first 10 min. A four-fold elevation of the secretion and concentration was observed in the bile of ligated rats compared with that of control animals. We next examined lanthanum permeability by perfusion fixation of the liver. At 6 h after ligation, both dilation of the bile canaliculi and partial loss of microvilli were commonly observed. There were dense deposits of lanthanum in almost all bile canaliculi of ligated rats. In control animals, neither dilation of the bile canaliculi nor loss of microvilli was detected, and only 44% of bile canaliculi exhibited deposits. An apparent increase of occludin mRNA expression was detected in livers after 6 h ligation, whereas the expression of claudin-1, -2, and -3 was not influenced by ligation. These results indicate that regulation of occludin gene expression is different from that of claudin-1, -2, and -3. The early phase of bile stasis employed in this study is thought to be an indispensable approach for understanding the precise regulation of tight junctions.


Study of the antitumor potential of Bidens pilosa (Asteraceae) used in Brazilian folk medicine.
Bidens pilosa (L.) (Asteraceae) is a medicinal plant traditionally used in Brazil for treating conditions that can be related to cancer. Therefore the present study was carried out to evaluate the antitumor activity of extracts obtained from the aerial parts of this plant species. The crude hydroalcoholic extract (HAE) (water:alcohol, 6:4) and solvent fractions (chloroform=CHCl3,ethyl acetate=EtOAc, methanol=MeOH) were assessed for cytotoxicity assay by the brine shrimp and hemolytic, MTT and NRU assays. The antiproliferative potential of the crude extract and fractions was investigated in vivo using the Ehrlich ascites carcinoma (EAC) in isogenic Balb/c mice that were administered intraperitoneally 150 and 300 mg/kg body weight per day for nine days beginning 24 h after tumor inoculation. In in vitro cytotoxicity using Ehrlich ascites carcinoma cell line assay CHCl3 extract proved to be more toxic than the crude HAE with an IC(50) of 97+/-7.2 and 83+/-5.2 microg/mL to NRU and MTT, respectively. Histomorphological evaluations indicated that the treatment with CHCl3 and HAE extracts significantly reduced (P<0.05) body weight, abdominal circumference, tumor volume, packed cell volume and viable cell count, when compared to EAC control group. Furthermore, nonviable tumor cell count increased significantly (P<0.01) only under treatment with CHCl3 or HAE, and this was accompanied by a marked percentage increase in life span (54.2 and 41.7%, respectively). Biochemical assays revealed that CHCl3 and HAE extracts were also able to decrease serum LDH activity (39.5 and 30.6%) and GSH concentration (94.6 and 50.7%) in ascitic fluid, respectively. The chloroform fraction showed the best and methanolic the worst antitumor activity.


How to achieve rapid separations in counter-current chromatography.
A new generation of high performance coil planet centrifuges is now making it possible to realize the enormous potential of liquid-liquid partition chromatography for the rapid and predictable scale up of separation processes. This paper uses a separation of flavonoids to demonstrate how rapid fractionations can be obtained at high flow rates with limited loss of resolution and with significant increase in throughput. Furthermore, it is shown that chromatograms at various flows can be modeled so that optimum conditions can be rapidly assessed.


Effect of Fear, Treatment, and Hunting Cooperation on an Eco-Epidemiological Model: Memory Effect in Terms of Fractional Derivative.
In this paper, we have studied a fractional-order eco-epidemiological model incorporating fear, treatment, and hunting cooperation effects to explore the memory effect in the ecological system through Caputo-type fractional-order derivative. We have studied the behavior of different equilibrium points with the memory effect. The proposed system undergoes through Hopf bifurcation with respect to the memory parameter as the bifurcation parameter. We perform numerical simulations for different values of the memory parameter and some of model parameters. In the numerical results, it appears that the system is exhibiting a stable behavior from a period or chaotic nature with the increase in the memory effect. The system also exhibits two transcritical bifurcations with respect to the growth rate of the prey. At low values of prey's growth, all species go to extinction, at moderate values of prey's growth, only preys (susceptible and infected) can survive, and at higher values of prey's growth, all species survive simultaneously. The paper ended with some recommendations.


Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation.
The objective of this research was to modify the crystal shape and size of poorly water-soluble drug ropivacaine, and to reveal the effects of polymeric additive and ultrasound on crystal nucleation and growth. Ropivacaine often grow as needle-like crystals extended along the a-axis and the shape was hardly controllable by altering solvent types and operating conditions for the crystallization process. We found that ropivacaine crystallized as block-like crystals when polyvinylpyrrolidone (PVP) was used. The control over crystal morphology by the additive was related to crystallization temperature, solute concentration, additive concentration, and molecular weight. SEM and AFM analyses were performed providing insights into crystal growth pattern and cavities on the surface induced by the polymeric additive. In ultrasound-assisted crystallization, the impacts of ultrasonic time, ultrasonic power, and additive concentration were investigated. The particles precipitated at extended ultrasonic time exhibited plate-like crystals with shorter aspect ratio. Combined use of polymeric additive and ultrasound led to rice-shaped crystals, which the average particle size was further decreased. The induction time measurement and single crystal growth experiments were carried out. The results suggested that PVP worked as strong nucleation and growth inhibitor. Molecular dynamics simulation was performed to explore the action mechanism of the polymer. The interaction energies between PVP and crystal faces were calculated, and mobility of the additive with different chain length in crystal-solution system was evaluated by mean square displacement. Based on the study, a possible mechanism for the morphological evolution of ropivacaine crystals assisted by PVP and ultrasound was proposed.


The pervasiveness of microplastic contamination in the gastrointestinal tract of fish from the western coast of Bangladesh.
This study investigated the prevalence of microplastics (MPs) in the gastrointestinal tract (GIT) of fish from the western coast of Bangladesh, the world's largest mangrove ecosystem. Altogether, 8 different species of fish (5 demersal and 3 pelagic) were examined. Microplastics were detected in every individual fish with an average abundance of 7.1 ± 3.14 particles per specimen. The demersal species were observed to consume more microplastics (7.78 ± 3.51) than the pelagic species (5.92 ± 2.06). Moreover, small-sized fish was found to accumulate higher MPs/body weight than large-sized fish. Polypropylene was the most abundant polymer type (45 %) and fiber was the most prevalent shape (71 %). SEM analysis revealed cracks, pits, and foreign particles on the microplastics' surface, representing their ability to bear organic pollutants and heavy metals. This study will be a source of information for future research and a guide for policy-makers to take better actions to protect and restore marine resources.


Individual differences in neural regions functionally related to real and imagined stuttering.
Recent brain imaging investigations of developmental stuttering show considerable disagreement regarding which regions are related to stuttering. These divergent findings have been mainly derived from group studies. To investigate functional neurophysiology with improved precision, an individual-participant approach (N=4) using event-related functional magnetic resonance imaging and test-retest reliability measures was performed while participants produced fluent and stuttered single words during two separate occasions. A parallel investigation required participants to imagine stuttering or not stuttering on single words. The overt and covert production tasks produced considerable within-subject agreement of activated voxels across occasions, but little within-subject agreement between overt and covert task activations. However, across-subject agreement for regions activated by the overt and covert tasks was minimal. These results suggest that reliable effects of stuttering are participant-specific, an implication that might correspond to individual differences in stuttering severity and functional compensation due to related structural abnormalities.


ROS: really involved in oxygen sensing.
The role of reactive oxygen species (ROS) in the cellular response to cellular oxygen sensing has been controversial. Three papers in this issue of Cell Metabolism (Brunelle et al., Guzy et al., 2005; Mansfield et al., 2005) used genetic tools to establish that ROS produced by mitochondria are required for the normal induction of HIF (hypoxia-inducible factor), which is a master regulator of oxygen-sensitive gene expression, by low oxygen.


Chromosome studies of bone marrow cells and peripheral blood lymphocytes from diphenylhydantoin-treated patients.
Chromosome studies were performed on both bone-marrow cells and peripheral blood lymphocytes from ten patients with epilepsy, treated with diphenylhydantoin alone. There was no evidence of chromosome damage. Furthermore, the bone-marrow smears from five of the patients were studied for the presence of micronuclei. There was no increase in the number of micronuclei compared with control persons. Conflicting results about the cytogenetic effect of diphenylhydantoin have appeared in the literature. It is emphasized that, in studies on the chromosome-damaging effect of chemical agents in man, bone marrow cells seem to be most indicative of the conditions in vivo.


Crystallization and preliminary X-ray studies of L-aspartase from Escherichia coli.
Single crystals of L-aspartate ammonia-lyase (L-aspartase) from Escherichia coli have been obtained by microdialysis at room temperature using polyethylene glycol 3350 and sodium acetate as co-precipitants. The crystals exhibit the symmetry of space group P2(1)2(1)2 with a = 156.5 A, b = 147.6 A, c = 102.5 A and diffract at least to 2.8 A.


Effect of atropine and acetylcholine on nerve stimulated output of noradrenaline and dopamine-beta-hydroxylase from isolated rabbit and guinea pig hearts.
The role of a cholinergic muscarinic inhibitory mechanism in sympathetic neurotransmission was investigated in isolated rabbit and guinea pig hearts with intact sympathetic nerves. The effect of varying frequencies of stimulation (2.5, 5 and 10 Hz) on the concentration of noradrenaline (NA) and dopamine-beta-hydroxylase (DBH) released into the perfusate was investigated. Stimulation in the presence of atropine sulfate (3.4 micrometer) resulted in an augmented outflow of NA at all three frequencies while DBH outflow was significantly incrreased only at 5 and 10 Hz. d-Tubocurarine (2.0 micrometer) attenuated the augmenting effect of atropine on NA release at all frequencies of stimulation whereas it negated the significant effect of atropine on DBH release. Nerve stimulation in the presence of acetylcholine (0.55 micrometer) resulted in a significant decrease in the concentrations of NA and DBH in the perfusate. It is suggested that atropine augments NA outflow in part by blocking an "intrinsic" muscarinic inhibitory mechanism. Acetylcholine's inhibitory effect on NA release is reflected in a similar decrease in DBH release and, therefore, may function in vivo via an effect on exocytosis at the adrenergic nerve ending.


Impaired interhemispheric synchrony in Parkinson's disease with depression.
The alterations of interhemispheric resting-state functional connectivity (FC) in Parkinson's disease (PD) with depression remain unclear, so we aimed to explore the differences of interhemispheric FC between PD with and without depression. Twenty-one depressed PD (DPD) patients, 49 non-depressed PD (NDPD) patients and 50 matched healthy controls (HC) participated in this study. Resting-state functional magnetic resonance imaging (fMRI) data were analyzed with the voxel-mirrored homotopic connectivity (VMHC) approach. The DPD patients showed lower VMHC values in the bilateral dorsolateral prefrontal cortex (DLPFC) and calcarine cortex compared to both NDPD and HC groups, and further receiver operating characteristic curves (ROC) analyses revealed that the VMHC in these two brain areas could be used as biomarkers to distinguish DPD from NDPD and from HC. The pooled PD patients (both DPD and NDPD) exhibited decreased VMHC in the bilateral putamen, middle occipital gyrus (MOG), postcentral gyrus (PoCG), paracentral lobule (PCL) and cerebellum posterior lobe when compared with HC. Decreased VMHC values within the DLPFC and calcarine cortex appeared to be unique features for DPD and might be used as potential neuroimaging markers to distinguish DPD patients from NDPD and HC groups. These findings may underlie the neural mechanisms of depression in PD.


Nutritional status, nutrient intake and use of enzyme supplements in paediatric patients with Cystic Fibrosis; a European multicentre study with reference to current guidelines.
The New European guidelines have established the most updated recommendations on nutrition and pancreatic enzyme replacement therapy (PERT) in CF. In the context of MyCyFAPP project - a European study in children with CF aimed at developing specific tools for improvement of self-management - the objective of the current study was to assess nutritional status, daily energy and macronutrient intake, and PERT dosing with reference to these new guidelines. Cross sectional study in paediatric patients with CF from 6 European centres. SD-scores for weight-for-age (WFA), height-for-age (HFA) and body mass index-for-age (BMI) were obtained. Through a specific 4-day food and enzyme-dose record, energy and macronutrients intake and PERT-use (LU/g lipids) were automatically calculated by the MyCyFAPP system. Comparisons were made using linear regression models. The lowest quartiles for BMI and HFA were between 0 and -1SD in all the centres with no significant differences, and 33.5% of the patients had a SD-score <0 for all three parameters. The minimum energy intake recommendation was not reached by 40% of the children and mean nutrients intake values were 14%, 51% and 34% of the total energy for protein, carbohydrates and lipids respectively. When assessed per centre, reported PERT doses were in the recommended range in only 13.8% to 46.6% of the patients; from 5.6% up to 82.7% of children were above the recommended doses and 3.3% to 75% were below. Among the 6 centres, a large variability and inconsistency with new guidelines on nutrition and PERT-use was found. Our findings document the lack of a general criterion to adjust PERT and suggest the potential benefit of educational and self-managerial tools to ensure adherence to therapies, both for clinical staff and families. They will be taken into account when developing these new tools during the next stages of MyCyFAPP Project.


Single-Use versus Reusable Endoscopes for Percutaneous Biliary Endoscopy with Lithotripsy: Technical Metrics, Clinical Outcomes, and Cost Comparison.
To compare procedure and fluoroscopy time, technical and clinical success, and costs between single-use and reusable endoscopes in patients undergoing percutaneous biliary endoscopy (PBE) with lithotripsy. Thirty-four patients (67 procedures) were retrospectively included in the study. The patients were treated with PBE for gallstone removal from October 24, 2014, to February 12, 2020, using reusable (28 procedures) or single-use (39 procedures) endoscopes. The procedure time, fluoroscopy time, technical success rate (accessing the biliary system and locating the gallstone), clinical success rate (at least partial gallstone removal), complication rate, and cost of use were compared between the procedures. The mean (± standard deviation) procedure time was not significantly different between single-use (136 minutes ± 45) and reusable endoscopes (136 minutes ± 51) (P = .47). The mean fluoroscopy time was significantly shorter for single-use endoscopes (11 minutes ± 8.4) than for reusable endoscopes (18 minutes ± 12) (P = .01). When comparing single-use versus reusable endoscopes, the technical success (95% [n = 37] vs 93% [n = 26]) and the clinical success (90% [n = 35] vs 75% [n = 21]) rates were not significantly different (both, P > .05). Only 1 complication was noted in the reusable endoscope group (P = .42). The cost per case was lower for single-use ($1,500) than for reusable ($3,987) endoscope procedures, primarily due to differences in capital costs and repair costs. Single-use endoscopes offer the potential for lower patient radiation exposure and lower cost per case, which may reduce the financial barriers to offering PBE in interventional radiology practices. The clinical and technical success rates did not differ by endoscope type.


Allergic rhinitis--current pharmacotherapy.
The use of pharmacotherapy for allergic rhinitis remains a central strategy in the integrated treatment of the patient. The most appropriate medical therapy depends upon the nature of specific rhinitis symptoms, patient tolerance to and preference for certain classes of medications, and response to treatment. Through an appreciation of these various physiological mechanisms, the physician can select the treatment option or options that will be most likely to effectively manage symptoms.


Tebuconazole induced oxidative stress related hepatotoxicity in adult and larval zebrafish (Danio rerio).
Tebuconazole is widely used as fungicide and has frequently been detected at elevated concentrations in environmental media. To characterize the potential toxicity of tebuconazole on vertebrate and humans. Using zebrafish as a vertebrate model, the toxic effects in liver that produced by low-toxic concentrations of tebuconazole were assessed in adult zebrafish. We further focused on tebuconazole-induced toxicity and its possible mechanism in larval zebrafish using a hepatotoxicity assay. The induction of oxidative stress in adult fish was evaluated by superoxide dismutase (T-SOD), catalase (CAT), peroxidase (POD), glutathione S-transferase (GST) activity, and the increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio. Significantly increased enzyme activity was observed in the liver of male and female fish at both exposure and depuration stage. Exposure to maximum non-lethal (MNLC) concentration of tebuconazole from 72 to 120 h post-fertilization (hpf) affected the liver size and yolk retention in larval zebrafish. Decreased fluorescence intensity was observed in larval Tg(Apo14:GFP) zebrafish, indicating liver degeneration after tebuconazole treated. Histopathological examination confirmed the alterations in liver histoarchitecture in exposed zebrafish. Significant 1.28-fold and 1.65-fold increases in reactive oxygen species levels were observed in juveniles exposed to MNLC and lethal concentration 10 (LC10) group, respectively. The acridine orange staining assay showed that apoptotic cells occurred in the liver regions. These results indicated that tebuconazole exposure resulted in impacts on the ecological risk in fish and vertebrate. Overall, the present study suggested further research in needed to better understand the tebuconazole-induced toxicity mechanism that associated with oxidative stress.


M1-like macrophage contributes to chondrogenesis in vitro.
Cartilage tissues have poor self-repairing abilities. Regenerative medicine can be applied to recover cartilage tissue damage in the oral and maxillofacial regions. However, hitherto it has not been possible to predict the maturity of the tissue construction after transplantation or to prepare mature cartilage tissues before transplantation that can meet clinical needs. Macrophages play an important role in cartilage tissue regeneration, although the exact mechanisms remain unknown. In this study, we established and verified an in vitro experimental system for the direct co-culture of cell pellets prepared from mouse auricular chondrocytes and macrophages polarized into four phenotypes (M1-like, M1, M2-like, and M2). We demonstrate that cartilage pellets co-cultured with M1-like promoted collagen type 2 and aggrecan production and induced the most significant increase in chondrogenesis. Furthermore, M1-like shifted to M2 on day 7 of co-culture, suggesting that the cartilage pellet supplied factors that changed the polarization of M1-like. Our findings suggest that cartilage regenerative medicine will be most effective if the maturation of cartilage tissues is induced in vitro by co-culture with M1-like before transplantation.


Results of systemic chemotherapy of advanced bladder carcinomas (phase II study).
At the time of operation advanced carcinomas of the urinary bladder often have developed subclinical metastases. In 20 patients with metastases, inoperable carcinoma of the bladder responded to chemotherapy with a combination of adriamycin and 5-FU. 55% of the patients experienced either a complete or incomplete remission, which lasted long in some cases. In the future, suitable combinations of chemotherapeutics could participate in improving the prognosis of advanced carcinoma of the urinary bladder.


Activity of compounds derived from benzofuroxan in Trichomonasvaginalis.
Trichomoniasis is a sexually transmitted infection caused by the protozoan Trichomonas vaginalis. Currently, trichomoniasis is treated with the class of nitroimidazoles, namely, metronidazole; however, resistant isolates and strains have been reported. The compounds derived from benzofuroxan are biologically active heterocycles. This study evaluated the in vitro antiparasitic activity of these compounds in trophozoites of T. vaginalis and determined the mean inhibitory concentration (IC50), minimum inhibitory concentration (MIC), mortality curve, and cytotoxicity. The compounds were named EH1, EH2, EH3, and EA2 and tested in various concentrations: 100 to 15 μM (EH1 and EH2); 100 to 5 μM (EH3); and 100 to 25 μM (EA2), respectively. The greatest efficacy was observed in the highest concentrations in 24 h, with inhibition of approximately 100% of trophozoites. Compounds EH2 and EH3 had the lowest MIC: EH2 (35 μM) and EH3 (45 μM), with IC50 of 11.33 μM and 6.83 μM, respectively. Compound EA2 was effective at the highest concentrations. The activity of the compounds in T. vaginalis started in the first hour of incubation with 90% inhibition; after 12 h, inhibition >95% was observed. Compound EH1 showed the lowest activity, with the highest activity between 12 and 24 h after incubation. These results demonstrate that benzofuroxan derivatives are promising compounds for the in vitro treatment of T. vaginalis.


Redox-induced protein structural changes in cytochrome bo revealed by Fourier transform infrared spectroscopy and [13C]Tyr labeling.
Cytochrome bo is a heme-copper terminal ubiquinol oxidase of Escherichia coli under highly aerated growth conditions. Tyr-288 present at the end of the K-channel forms a Cepsilon-Nepsilon covalent bond with one of the Cu(B) ligand histidines and has been proposed to be an acid-base catalyst essential for the O-O bond cleavage at the Oxy-to-P transition of the dioxygen reduction cycle (Uchida, T., Mogi, T., and Kitagawa, T. (2000) Biochemistry 39, 6669-6678). To probe structural changes at tyrosine residues, we examined redox difference Fourier transform infrared difference spectra of the wild-type enzyme in which either L-[1-13C]Tyr or L-[4-13C]Tyr has been biosynthetically incorporated in the tyrosine auxotroph. Spectral comparison between [1-13C]Tyr-labeled and unlabeled proteins indicated that substitution of the main chain carbonyl of a Tyr residue(s) significantly affected changes in the amide-I (approximately 1620-1680 cm(-1)) and -II ( approximately 1540-1560 cm(-1)) regions. In contrast, spectral comparison between [4-13C]Tyr-labeled and unlabeled proteins showed only negligible changes, which was the case for both the pulsed and the resting forms. Thus, protonation of an OH group of tyrosines including Tyr-288 in the vicinity of the heme o-Cu(B) binuclear center was not detected at pH 7.4 upon full reduction of cytochrome bo. Redox-induced main chain changes at a Tyr residue(s) are associated with structural changes at Glu-286 near the binuclear metal centers and may be related to switching of the K-channel operative at the reductive phase to D-channel at the oxidative phase of the dioxygen reduction cycle via conformational changes in the middle of helix VI.


Inspiratory stridor and dysphagia because of prolonged oesophageal foreign body.
A 2-year-old boy with severe inspiratory stridor and dysphagia is described. The delay in the diagnosis of an impacted foreign body resulted in severe deformation of the oesophagus. After surgical extraction of the foreign body the oesophagus was splinted for 4 months by a nasogastric tube because of persistent severe dysphagia. Removal of this tube was followed by a gradual disappearance of the complaints.


Synthesis of oriented arrays of TiO2 nanorods via a high temperature conversion of carbon nanotubes.
Oriented arrays of both rutile and anatase nanorods have been synthesised in a two-stage process, employing multi-walled carbon nanotubes as the initial structural template.


Students' age profile sparks fears about deterrent effect of loans.
Almost one in four nursing students is 30 or older - raising fresh concern about changes to their funding.


Are the impacts of renewable energy use on load capacity factors homogeneous for developed and developing nations? Evidence from the G7 and E7 nations.
Both developed and underdeveloped economies worldwide are now more concerned than ever in respect of achieving environmental sustainability. Accordingly, the majority of the global economies have ratified several environment-related pacts to facilitate the tackling of global environment-related problems. Although these problems are assumed to be addressed using diverse mechanisms, limiting the use of fossil fuels has often been recognized as the ultimate enabler of environmental sustainability. Against this backdrop, this study aims to assess the environmental impacts associated with higher renewable energy use, controlling for economic growth and population size, in the context of the G7 and E7 countries using data from 1997 to 2018. Moreover, instead of using the traditional environmental quality proxies, this study tries to proxy environmental degradation with the load capacity factor levels of the countries of concern. The long-run associations among the study's variables are confirmed by outcomes generated from the cointegration analysis. Besides, regression analysis highlighted that integrating renewable energy into the energy systems while withdrawing from the use of fossil fuels can help to improve environmental quality by increasing the load capacity factor levels. In contrast, economic growth and population size expansion are evidenced to impose environmental quality-dampening impacts by reducing the load capacity factor levels. However, the findings, in the majority of the cases, are seen to differ across the groups of the G7 and E7 countries, especially in terms of the variations in the magnitudes of marginal environmental effects over the short and long run. Lastly, the causality analysis confirms the directions of the causal relationships among the variables of concern. Based on these results, a couple of policy interventions are recommended for improving environmental quality in the G7 and E7 countries.


Hematological alterations and thymic function in newborns of HIV-infected mothers receiving antiretroviral drugs.
To investigate the effects of antiretroviral (ARV) drugs on hematological parameters and thymic function in HIV-uninfected newborns of HIV-infected mothers. Cross sectional study. Chiang-Mai University Hospital, Chiang-Mai, Thailand. 49 HIV-uninfected and 26 HIV-infected pregnancies. Cord blood samples of newborns from HIV-uninfected and HIV-infected mothers were collected. Hematological parameters were measured using automatic blood cell count. T-cell receptor excision circles (TRECs) levels in cord blood mononuclear cells (CBMCs), CD4+ and CD8+ T-cells were quantified using real-time PCR.. Hemotological parameters and thymic function. Newborn of HIV-infected mother tended to have lower mean levels of hemoglobin than those of HIV-uninfected mother (137 ±22 vs 146 ±17 g/L, P = 0.05). Furthermore, mean of red blood cell (RBC) counts and hematocrit and median of TRECs in CD4+ T-cells in the newborns of the former were significantly lower than those of the latter [3.6 ±0.7 vs 4.8 ±0.6 x 1012 cells/L, P <0.001; 0.40 ±0.07 vs 0.46 ±0.05 L/L, P < 0.001 and 0.53 (IQR: 0.03-5.76) vs 13.20 (IQR: 2.77-27.51) x 10-3 pg/uL, P = 0.02, respectively]. ARV drugs altered hematological parameters and thymic function (TRECs CD4+ T-cells) in HIV-uninfected newborns of HIV-infected mothers.


Possible links between gut-microbiota and attention-deficit/hyperactivity disorders in children and adolescents.
An association between gut-microbiota and several neuropsychiatric conditions including autism, depression, anxiety, schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) has been observed. Despite being the most prevalent neurodevelopmental disorders in children and adolescents worldwide, the etiology and curative approaches to treatment of ADHD remain unclear. There is a probability that gut-microbiota may contribute to ADHD via bidirectional communication between the gut and brain, a system known as the "gut-brain axis". Although a mechanistic link in the gut-brain axis in ADHD has been proposed, there is still a lack of information about the correlation of the microbiome profile with the mechanisms involved. The objective of this review was to summarize the diversity of the gut-microbiota and taxonomic profiles in children and adolescents with ADHD. In this review, we have provided an overview of the association between ADHD and gut-microbiota. The evidence pertinent to potentially distinctive gut-microbiota in children and adolescents with ADHD is also discussed and compared to that of their non-ADHD peers. Finally, the implications and future directions for investigation into the gut microbiome in ADHD patients are proposed.


Some key issues in building a "source network load storage" complementary energy internet in China.
The key to "dual carbon" lies in low-carbon energy systems. The energy internet can coordinate upstream and downstream "source network load storage" to break energy system barriers and promote carbon reduction in energy production and consumption processes. This article first introduces the basic concepts and key technologies of the energy internet from the current situation of energy supply and demand in China. Second, this paper proposes to create an energy internet with coordinated and complementary "source network load storage" and to construct a new type of power system with six new characteristics in this context. Finally, combined with an example of the energy internet demonstration project, this paper analyses and summarizes the value creation and business type innovation of the energy internet from three aspects: power market mechanisms, comprehensive energy services, and low-carbon energy diversification, and it looks ahead to the future direction of energy internet construction.


What lies within: phenomenology and intuitive self-knowledge.
This article discusses the significance of intuitiveness as a component of phenomenological knowing and demonstrates how this way of knowing may exist independently of or coexist collaboratively with rationality and evidence-based practice. By using a holistic approach to knowing, nurses use clinical reasoning skills to prevent adverse patient outcomes from failure to diagnose problems, to establish appropriate treatments, and/or to deal with complications. As the complexity of health care escalates, health care providers must strive to think holistically to advance knowledge and contribute to their discipline. The discipline of nursing requires holistic thought and innovative interventions.


Using Diet to Treat Diseases of Esophagus: Back to the Basics.
The esophagus plays a crucial role in oral nutrition and digestive pathophysiology. In addition, diet is now considered an important primary or augmentative therapy in several esophageal disease states. This review highlights common dietary therapies used in treating diseases of the esophagus as well as the underlying data that support such practices. Specially, diet and its relationship to swallowing dysfunction, motility disorders, malignancies, and inflammatory mucosal diseases such as gastroesophageal reflux disease and eosinophilic esophagitis is explored.


Tailoring the Electronic Structure of an Atomically Dispersed Zinc Electrocatalyst: Coordination Environment Regulation for High Selectivity Oxygen Reduction.
Accurately regulating the selectivity of the oxygen reduction reaction (ORR) is crucial to renewable energy storage and utilization, but challenging. A flexible alteration of ORR pathways on atomically dispersed Zn sites towards high selectivity ORR can be achieved by tailoring the coordination environment of the catalytic centers. The atomically dispersed Zn catalysts with unique O- and C-coordination structure (ZnO3 C) or N-coordination structure (ZnN4 ) can be prepared by varying the functional groups of corresponding MOF precursors. The coordination environment of as-prepared atomically dispersed Zn catalysts was confirmed by X-ray absorption fine structure (XAFs). Notably, the ZnN4 catalyst processes a 4 e- ORR pathway to generate H2 O. However, controllably tailoring the coordination environment of atomically dispersed Zn sites, ZnO3 C catalyst processes a 2 e- ORR pathway to generate H2 O2 with a near zero overpotential and high selectivity in 0.1 M KOH. Calculations reveal that decreased electron density around Zn in ZnO3 C lowers the d-band center of Zn, thus changing the intermediate adsorption and contributing to the high selectivity towards 2 e- ORR.