Ventricular arrhythmias in children with an apparently normal heart.
Ventricular ectopy occurs frequently in normal children. In the presence of a normal heart, these arrhythmias, including asymptomatic, nonsustained ventricular tachycardia, carry a benign prognosis and are not associated with sudden, unexpected death. However, complex ventricular arrhythmias frequently indicate the presence of underlying cardiac disease; patients with such arrhythmias must undergo an appropriately thorough evaluation before decisions regarding prognosis and the need for therapy can be made.


Antimicrobial Activity of Microgels with an Immobilized Copper(II) Complex Linked to Cross-Linking and Composition.
The resistance of many bacteria against currently available antimicrobial agents is increasing worldwide at an alarming pace. The described structure-activity relationship study was prompted by the extraordinary ability of water-dispersed microgels to hydrolyze glycosidic bonds similar to building blocks of the peptidoglycan layer of Gram-positive bacteria. The results establish polyacrylate microgels with embedded copper(II) complex as antimicrobial agents. The systematic study reveals that Staphylococcus aureus is susceptible to the microgels, while common commercial agents are found intermediate or resistant. In particular, a microgel with 60 mol % of cross-linking, Cu2LP60%, shows intriguing bactericidal activity at 1 μg/mL, while vancomycin requires a 4-fold higher dose, i.e., 4 μg/mL, for the same effect. The minimum inhibitory concentration of Cu2LP60% was determined as low as 0.64 μg/mL. Excellent stability of the poly(acrylate) microgels was observed by negative zeta potentials in nanopure water and aqueous sodium dodecyl sulfate solution. The composition of the microgel matrix with embedded binuclear metal complex was shown to be responsible for the antimicrobial activity, while the aqueous buffer-surfactant solution is not.


Spatial localization of absorbing bodies by interfering diffusive photon-density waves.
The use of the destructive interference of diffusive photon-density waves for the localization of an absorbing (and scattering) body in a scattering medium was studied. The objectives of this approach in the reflectance mode were as follows: first, to reduce sensitivity to absorption features occurring in superficial layers while sensitivity to bodies lying deeper is maintained; second, to establish a confined depth region of maximum sensitivity in which the distance of an absorbing body could be determined through phase measurement. Intensity and phase data were acquired with a modified frequency-domain spectrometer at modulation frequencies up to 600 MHz as an absorbing body was moved in three dimensions. The experimental results are compared with simulations based on a numerical solution of a time-dependent photon-diffusion equation.


RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells.
Knowledge of the expression profile and spatial landscape of the transcriptome in individual cells is essential for understanding the rich repertoire of cellular behaviors. Here, we report multiplexed error-robust fluorescence in situ hybridization (MERFISH), a single-molecule imaging approach that allows the copy numbers and spatial localizations of thousands of RNA species to be determined in single cells. Using error-robust encoding schemes to combat single-molecule labeling and detection errors, we demonstrated the imaging of 100 to 1000 distinct RNA species in hundreds of individual cells. Correlation analysis of the ~10(4) to 10(6) pairs of genes allowed us to constrain gene regulatory networks, predict novel functions for many unannotated genes, and identify distinct spatial distribution patterns of RNAs that correlate with properties of the encoded proteins.


Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy.
To examine the safety and efficacy of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone. Treatment-naive patients or those receiving metformin, sulfonylurea, or thiazolidinedione entered a 10-week pioglitazone dose-optimization period with only pioglitazone. They were then randomized, along with patients previously receiving pioglitazone ≥30 mg, to 48 weeks of double-blind dapagliflozin 5 (n = 141) or 10 mg (n = 140) or placebo (n = 139) every day plus open-label pioglitazone. The primary objective compared HbA(1c) change from baseline with dapagliflozin plus pioglitazone versus placebo plus pioglitazone at week 24. Primary analysis was based on ANCOVA model using last observation carried forward; all remaining analyses used repeated-measures analysis. At week 24, the mean reduction from baseline in HbA(1c) was -0.42% for placebo versus -0.82 and -0.97% for dapagliflozin 5 and 10 mg groups, respectively (P = 0.0007 and P < 0.0001 versus placebo). Patients receiving pioglitazone alone had greater weight gain (3 kg) than those receiving dapagliflozin plus pioglitazone (0.7-1.4 kg) at week 48. Through 48 weeks: hypoglycemia was rare; more events suggestive of genital infection were reported with dapagliflozin (8.6-9.2%) than placebo (2.9%); events suggestive of urinary tract infection showed no clear drug effect (5.0-8.5% for dapagliflozin and 7.9% for placebo); dapagliflozin plus pioglitazone groups had less edema (2.1-4.3%) compared with placebo plus pioglitazone (6.5%); and congestive heart failure and fractures were rare. In patients with type 2 diabetes inadequately controlled on pioglitazone, the addition of dapagliflozin further reduced HbA(1c) levels and mitigated the pioglitazone-related weight gain without increasing hypoglycemia risk.


[Determination of glutathione-S-transferase activity in Culex quinquefaciatus strains in Cuba and other Latin American countries].
In the present paper, we standardized a microtitration assay for the determination of specific activity of glutathione-S-transferase using a Culex quinquefasciatus strain selected in lab with pyrethroid insecticide lambdacyhalothrin for 6 generations (SP6). The saturation values for reduced glutathione and 1-chlorine 2,4-dinitrobenzene were 15 mM and 40 mM, respectively; we also estimated that 3 minutes was the optimal time in order to differentiate resistant strain SP6 from the susceptible reference strain S-Lab (p>0.05). Additionally, the optimized microtitration method allowed testing 4 Culex strains from Cuba (SANTIAGO DE CUBA, SD4, QUIBU AND SP6), one from Venezuela (MIRANDA), one from Colombia (MEDELLIN) and the other from Brazil (RIO DE JANEIRO) for glutathione-S-transferase activity. MIRANDA showed the highest activity for this detoxifying enzyme. However, the mechanism of detoxyfication in all the strains was very unfrequent, which indicates that its role in resistance to insecticide for all the studied strains is not so important. Glutathione-S-transferase values were compared with non-specific esterase and altered acetylcholinesterase frequencies for each of the studied strains.


Genetic variation in the incidence of pipped eggs in turkeys selected for low and high semen ejaculate volume.
Genetic variation in embryonic mortality, expressed as embryos that pip their eggshell but do not hatch, was investigated in turkeys selected for low and high semen ejaculate volume (SEV). Through five generations (Generations 10 to 14, inclusive) mean heritability estimates for pipped eggs were .21 and .08 in the low- and high-SEV lines, respectively. Estimates of sire, dam, and within-hatch components of variance suggest greater environmental and maternal effects than genetic influences on the incidence of pipped eggs in turkeys.


Organization of the human transferrin gene: direct evidence that it originated by gene duplication.
We present the characterization of two overlapping human transferrin genomic clones isolated from a liver DNA library. The two clones represent a total length of 24 kilobase pairs and code for 70% of the protein. The organization of this gene region was elucidated by restriction mapping and DNA sequencing. It contains 12 exons, ranging from 33 to 181 base pairs, separated by introns of 0.7-4.9 kilobase pairs. This gene can be divided into two unequal parts corresponding to the known domains of the protein. Each part is essentially composed of an equal number of exons; introns interrupt the coding sequences, creating homologous exons of similar size in each moiety. Moreover, the pattern of intron interruption of the codon sequence is identical for all the analyzed homologous exon pairs. Comparison with the organization of the ovotransferrin gene shows an identical exon size distribution. These data confirm, at the gene level, the hypothesis that transferrins originated by a gene-duplication event. A model accounting for the origin of the human transferrin gene is presented.


Soluble MICB in Plasma and Urine Explains Population Expansions of NKG2D+CD4 T Cells Inpatients with Juvenile-Onset Systemic Lupus Erythematosus.
Abnormal NKG2D ligand expression has been implicated in the initiation and maintenance of various auto-inflammatory disorders including systemic lupus erythematosus (SLE). This study's goal was to identify the cellular contexts providing NKG2D ligands for stimulation of the immunosuppressive NKG2D+CD4 T cell subset that has been implicated in modulating juvenile-onset SLE disease activity. Although previous observations with NKG2D+CD4 T cells in healthy individuals pointed towards peripheral B cell and myeloid cell compartments as possible sites of enhanced NKG2DL presence, we found no evidence for a disease-associated increase of NKG2DL-positivity among juvenile-onset SLE B cells and monocytes. However, juvenile-onset SLE patient plasma and matched urine samples were positive by ELISA for the soluble form of the NKG2D ligands MICA and MICB, suggesting that kidney and/or peripheral blood may constitute the NKG2DL positive microenvironments driving NKG2D+CD4 T cell population expansions in this disease.


Nitrification, denitrification, and related functional genes under elevated CO2 : A meta-analysis in terrestrial ecosystems.
Global change may have profound effects on soil nitrogen (N) cycling that can induce positive feedback to climate change through increased nitrous oxide (N2 O) emissions mediated by nitrification and denitrification. We conducted a meta-analysis of the effects of elevated CO2 on nitrification and denitrification based on 879 observations from 58 publications and 46 independent elevated CO2 experiments in terrestrial ecosystems. We investigated the effects of elevated CO2 alone or combined with elevated temperature, increased precipitation, drought, and N addition. We assessed the response to elevated CO2 of gross and potential nitrification, potential denitrification, and abundances of related functional genes (archaeal amoA, bacterial amoA, nirK, nirS, and nosZ). Elevated CO2 increased potential nitrification (+28%) and the abundance of bacterial amoA functional gene (+62%) in cropland ecosystems. Elevated CO2 increased potential denitrification when combined with N addition and higher precipitation (+116%). Elevated CO2 also increased the abundance of nirK (+25%) and nirS (+27%) functional genes in terrestrial ecosystems and of nosZ (+32%) functional gene in cropland ecosystems. The increase in the abundance of nosZ under elevated CO2 was larger at elevated temperature and high N (+62%). Four out of 14 two-way interactions tested between elevated CO2 and elevated temperature, elevated CO2 and increased precipitation, and elevated CO2 and N addition were marginally significant and mostly synergistic. The effects of elevated CO2 on potential nitrification and abundances of bacterial amoA and nirS functional genes increased with mean annual temperature and mean annual precipitation. Our meta-analysis thus suggests that warming and increased precipitation in large areas of the world could reinforce positive responses of nitrification and denitrification to elevated CO2 and urges the need for more investigations in the tropical zone and on interactive effects among multiple global change factors, as we may largely underestimate the effects of global change on soil N2 O emissions.


[The tissue and cellular reactions of the lung in drug-resistant tuberculosis].
The material obtained from 52 patients with drug-resistant fibrocavernous pulmonary tuberculosis was studied. Morphological studies established the progression of a process in 94.2% of the cases. There was a prevalence of an alternatively exudative tissue reaction, a generalization of the process with specific and non-specific changes in the lung, lesion to the vascular bed with a predominance of an exudative reaction, generalized nonspecific and specific bronchitis with impaired elimination of the intraalveolar contents and with the preserved extensive cellular infiltrates in the lung. Healing elements as the signs of the encapsulation of caseous necrosis, the proliferation of lymphoid elements, and a macrophageal response were simultaneously revealed, which provides evidence for that different modalities of pathogenetic therapy should be used.


The positive allosteric GABAB receptor modulator rac-BHFF enhances baclofen-mediated analgesia in neuropathic mice.
Neuropathic pain is associated with impaired inhibitory control of spinal dorsal horn neurons, which are involved in processing pain signals. The metabotropic GABAB receptor is an important component of the inhibitory system and is highly expressed in primary nociceptors and intrinsic dorsal horn neurons to control their excitability. Activation of GABAB receptors with the orthosteric agonist baclofen effectively reliefs neuropathic pain but is associated with severe side effects that prevent its widespread application. The recently developed positive allosteric GABAB receptor modulators lack most of these side effects and are therefore promising drugs for the treatment of pain. Here we tested the high affinity positive allosteric modulator rac-BHFF for its ability to relief neuropathic pain induced by chronic constriction of the sciatic nerve in mice. rac-BHFF significantly increased the paw withdrawal threshold to mechanical stimulation in healthy mice, indicating an endogenous GABABergic tone regulating the sensitivity to mechanical stimuli. Surprisingly, rac-BHFF displayed no analgesic activity in neuropathic mice although GABAB receptor expression was not affected in the dorsal horn as shown by quantitative receptor autoradiography. However, activation of spinal GABAB receptors by intrathecal injection of baclofen reduced hyperalgesia and its analgesic effect was considerably potentiated by co-application of rac-BHFF. These results indicate that under conditions of neuropathic pain the GABAergic tone is too low to provide a basis for allosteric modulation of GABAB receptors. However, allosteric modulators would be well suited as an add-on to reduce the dose of baclofen required to achieve analgesia.


Deoxyribonuclease-inhibitory antibodies in systemic lupus erythematosus.
Deoxyribonucleases (DNases) are key enzymes for digesting DNA. Abnormalities in the function of these enzymes may contribute to the development of anti-DNA antibodies in systemic lupus erythematosus (SLE). In this study, we used bovine DNase 1-coated ELISA plates to screen anti-DNase antibodies in SLE patients. About 62% of the sera of SLE patients (63/101) were positive for anti-DNase antibodies compared to only 8% of normal controls (8/98). A positive correlation was also found between the concentrations of anti-DNase and anti-DNA antibodies in sera of SLE patients. Affinity-purified anti-DNase immunoglobulin G (IgG) from pooled sera of SLE patients bound to bovine DNase as well as DNA. A synthetic peptide, corresponding to the catalytic site of DNase, was able to completely inhibit the binding of anti-DNase IgG to DNase. In addition to bovine DNase, the anti-DNase IgG also bound to and inhibited the enzymatic activities of DNase present in streptococcal supernatants and human urine. Immunization of lupus-prone NZB/NZW mice with bovine DNase enhanced the production of anti-DNase and DNA antibodies, and accelerated the occurrence of proteinuria. Taken together, these results suggest that DNase-inhibitory antibodies which recognize a conserved epitope near the catalytic site of DNase may act in the pathogenesis of SLE.


Laser varifocal system synthesis for longitudinal Gaussian beam shifting.
This paper presents a modeling approach of a laser varifocal system for longitudinal Gaussian beam waist shifting. The developed approach is based on laser optics theory, which is considered to be classical optics generalized for coherent radiation. A basic optical system, consisting of two components, was developed using this theory. Components have fixed focal lengths and specific movements. An automated modeling algorithm was proposed, and an example was provided in text. Various systems shown in this paper form a Gaussian beam with required waist parameters and provide its longitudinal shifts, which exceed the length of the near-zone of a focused Gaussian beam. Such systems can be used in laser technologies, including micro- and nano-sized objects manipulation.


Peroxisomal alterations in Alzheimer's disease.
In Alzheimer's disease (AD), lipid alterations are present early during disease progression. As some of these alterations point towards a peroxisomal dysfunction, we investigated peroxisomes in human postmortem brains obtained from the cohort-based, longitudinal Vienna-Transdanube Aging (VITA) study. Based on the neuropathological Braak staging for AD on one hemisphere, the patients were grouped into three cohorts of increasing severity (stages I-II, III-IV, and V-VI, respectively). Lipid analyses of cortical regions from the other hemisphere revealed accumulation of C22:0 and very long-chain fatty acids (VLCFA, C24:0 and C26:0), all substrates for peroxisomal β-oxidation, in cases with stages V-VI pathology compared with those modestly affected (stages I-II). Conversely, the level of plasmalogens, which need intact peroxisomes for their biosynthesis, was decreased in severely affected tissues, in agreement with a peroxisomal dysfunction. In addition, the peroxisomal volume density was increased in the soma of neurons in gyrus frontalis at advanced AD stages. Confocal laser microscopy demonstrated a loss of peroxisomes in neuronal processes with abnormally phosphorylated tau protein, implicating impaired trafficking as the cause of altered peroxisomal distribution. Besides the original Braak staging, the study design allowed a direct correlation between the biochemical findings and the amount of neurofibrillary tangles (NFT) and neuritic plaques, quantified in adjacent tissue sections. Interestingly, the decrease in plasmalogens and the increase in VLCFA and peroxisomal volume density in neuronal somata all showed a stronger association with NFT than with neuritic plaques. These results indicate substantial peroxisome-related alterations in AD, which may contribute to the progression of AD pathology.


Truncal vagotomy and pyloroplasty for duodenal ulcer.
Two hundred sixty-five patients who underwent vagotomy and pyloroplasty for duodenal ulcer disease were observed postoperatively, 220 for two to ten years, with an average follow-up of five years. Vagotomy and pyloroplasty carried a higher overall recurrence rate (3.6%) than did subtotal gastrectomy and vagotomy (1%), largely because of the high ulcer recurrence rate more than two years after operation for massive bleeding (9.2%) rather than that following elective operation (1.8%). Thirty-five percent of these patients with recurrent ulcers did well with medical management and did not require a second operation. The mortality of vagotomy and pyloroplasty for a massively bleeding ulcer (11%) was less than that following subtotal gastrectomy (21%). The mortality of elective vagotomy and pyloroplasty was 1%.


Associations of Cerebrovascular Regulation and Arterial Stiffness With Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis.
Cerebral small vessel disease (cSVD) is a major contributing factor to ischemic stroke and dementia. However, the vascular pathologies of cSVD remain inconclusive. The aim of this systematic review and meta-analysis was to characterize the associations between cSVD and cerebrovascular reactivity (CVR), cerebral autoregulation, and arterial stiffness (AS). MEDLINE, Web of Science, and Embase were searched from inception to September 2023 for studies reporting CVR, cerebral autoregulation, or AS in relation to radiological markers of cSVD. Data were extracted in predefined tables, reviewed, and meta-analyses performed using inverse-variance random effects models to determine pooled odds ratios (ORs). A total of 1611 studies were identified; 142 were included in the systematic review, of which 60 had data available for meta-analyses. Systematic review revealed that CVR, cerebral autoregulation, and AS were consistently associated with cSVD (80.4%, 78.6%, and 85.4% of studies, respectively). Meta-analysis in 7 studies (536 participants, 32.9% women) revealed a borderline association between impaired CVR and cSVD (OR, 2.26 [95% CI, 0.99-5.14]; P=0.05). In 37 studies (27 952 participants, 53.0% women) increased AS, per SD, was associated with cSVD (OR, 1.24 [95% CI, 1.15-1.33]; P<0.01). Meta-regression adjusted for comorbidities accounted for one-third of the AS model variance (R2=29.4%, Pmoderators=0.02). Subgroup analysis of AS studies demonstrated an association with white matter hyperintensities (OR, 1.42 [95% CI, 1.18-1.70]; P<0.01). The collective findings of the present systematic review and meta-analyses suggest an association between cSVD and impaired CVR and elevated AS. However, longitudinal investigations into vascular stiffness and regulatory function as possible risk factors for cSVD remain warranted.


Lessons from the Visual Acuity Impairment Survey pilot study.
The Visual Acuity Impairment Survey (VAIS) pilot study was carried out in three large metropolitan areas of the United States to determine whether it would be feasible to conduct a large two-stage survey of the prevalence of visual acuity impairment and its causes. The study was conducted in conjunction with the Health Interview Survey (HIS), performed by the National Center for Health Statistics and the Census Bureau. In the first stage, a simple vision screening test was administered to 1,868 adults in their homes by specially trained Census Bureau interviewers. All those who failed the test, and a sample of those who passed it, were invited to a local clinic for a check on the accuracy of the screen and a detailed eye examination to establish the cause of the impairment. About 89 per cent of the HIS interviewees took the vision screening test in the home and agreed to have the results released, making it possible for the clinic to invite them for an examination. The principal obstacle to the success of the feasibility study was a low rate (less than 50 per cent) of participation in the clinic examination by the target population. Such low participation would leave the survey open to a serious question about its representativeness. The methods and findings of the pilot study are presented because the lessons may be of value to those attempting similar studies in the future. Suggestions are made for methodological modifications that may enhance the chances for success.


Epstein-Barr virus coinfection in children boosts cytomegalovirus-induced differentiation of natural killer cells.
During childhood, infections with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) can occur in close temporal proximity. Active, as well as latent, CMV infection is associated with enlarged subsets of differentiated natural killer (NK) and cytotoxic T cells. How EBV infection may influence CMV-driven immune differentiation is not known. We found that EBV coinfection selectively influenced the NK cell compartment of CMV-seropositive (CMV(+)) children. Coinfected children had significantly higher proportions of peripheral-blood NKG2C(+) NK cells than CMV(+) EBV(-) children. Ex vivo NK cell degranulation after target cell stimulation and plasma IL-15 levels were significantly higher in CMV(+) children. EBV coinfection was related to the highest levels of plasma interleukin-15 (IL-15) and IL-12p70. Remarkably, in vitro EBV infection of peripheral blood mononuclear cells (PBMC) from EBV(-) CMV(+) children increased NKG2C(+) NK cell proportions. A similar tendency was seen in cocultures of PBMC with EBV(+) lymphoblastoid B-cell lines (LCL) and IL-15. After K562 challenge, NKG2C(+) NK cells excelled in regard to degranulation and production of gamma interferon, regardless of whether there was previous coculture with LCL. Taken together, our data suggest that dual latency with these herpesviruses during childhood could contribute to an in vivo environment supporting differentiation and maintenance of distinct NK cell populations. This viral imprint may affect subsequent immune responses through altered distributions of effector cells.


Changes of the level of G protein alpha-subunit mRNA by tolerance to and withdrawal from butorphanol.
Butorphanol was infused continuously into cerebral ventricle at a constant rate of 26 nmol/microl/h for 3 days, and the withdrawal from opioid was rendered 7 h after the cessation of infusion. The G-protein alpha-subunit has been implicated in opioid tolerance and withdrawal. The effects of continuous infusion of butorphanol on the modulation of G protein alpha-subunit mRNA were investigated by using in situ hybridization techniques. In situ hybridization showed marked changes in the levels of Galpha s during butorphanol tolerance and withdrawal. Specifically, the level of Galpha s mRNA was significantly decreased in almost all areas of brain except hippocampus during the butorphanol withdrawal. It was also decreased in the septum and cerebellar granule layer in butorphanol tolerant rats. The level of Galpha i mRNA was significantly decreased only in the cerebral cortex of butorphanol tolerant rat. However, no such change was noted during the withdrawal from butorphanol. The level of Galpha o mRNA was not changed either in butorphanol tolerant or in the butorphanol withdrawal rats. No alterations were noted in the level of [3H]forskolin binding to adenylyl cyclase in butorphanol tolerant as well as withdrawing rats. The levels of pCREB were significantly elevated in the hippocampus in the butorphanol withdrawal rats. These results suggest that region-specific changes of G protein alpha-subunit mRNA and pCREB without marked changes in the level of adenylyl cyclase may underlie the tolerance to and withdrawal from butorphanol.


Novel Combined Tissue Transcriptome Analysis After Lentogenic Newcastle Disease Virus Challenge in Inbred Chicken Lines of Differential Resistance.
Disease has large negative impacts on poultry production. A more comprehensive understanding of host-pathogen interaction can lead to new and improved strategies to maintain health. In particular, host genetic factors can lead to a more effective response to pathogens, hereafter termed resistance. Fayoumi and Leghorn chicken lines have demonstrated relative resistance and susceptibility, respectively, to the Newcastle disease virus (NDV) vaccine strain and many other pathogens. This biological model was used to better understand the host response to a vaccine strain of NDV across three tissues and time points, using RNA-seq. Analyzing the Harderian gland, trachea, and lung tissues together using weighted gene co-expression network analysis (WGCNA) identified important genes that were co-expressed and associated with parameters including: genetic line, days post-infection (dpi), challenge status, sex, and tissue. Pathways and driver genes, such as EIF2AK2, MPEG1, and TNFSF13B, associated with challenge status, dpi, and genetic line were of particular interest as candidates for disease resistance. Overall, by jointly analyzing the three tissues, this study identified genes and gene networks that led to a more comprehensive understanding of the whole animal response to lentogenic NDV than that obtained by analyzing the tissues individually.


Alcohol and hypertension--kill or cure?
An association between alcohol consumption and blood pressure levels has been observed in over 60 population studies world wide. The relationship is generally linear but with some studies showing a threshold effect at around 2-3 standard drinks a day. Effects are seen with all types of alcoholic beverages, and in men and women. The affect appears additive to effects of obesity and higher dose oral contraceptives. Studies of acute effects of alcohol suggest an initial vasodilator response, while population studies suggest that heavy drinkers may show some rebound hypertension. Randomized controlled trials show that reducing alcohol consumption lowers blood pressure in both treated and untreated hypertensives. Mechanisms of alcohol induced hypertension are still unclear. Despite predisposing to hypertension, regular light to moderate drinking (1-4 standard drinks a day) appears to protect against coronary deaths and ischaemic strokes, while heavier drinking increases the risk of haemorrhagic stroke and heart disease. There is some suggestion that wine drinking may be associated with lower cardiovascular risks, however in a study of 343 working men we found that beverage preference and drinking patterns correlated strongly with diet habits, smoking education and socioeconomic status, factors that are likely to confound the interpretation of epidemiological studies suggesting favourable cardiovascular effects to a particular beverage. Although light drinkers have lower mortality than non drinkers those drinking more than 2 standard alcohol drinks per day show a rising mortality as well as an increased risk of hypertension. Those facts should be the basis of public health advice on 'safe' levels of drinking.


Sensori-motor adaptation to knee osteoarthritis during stepping-down before and after total knee replacement.
Stepping-down is preceded by a shift of the center of mass towards the supporting side and forward. The ability to control both balance and lower limb movement was investigated in knee osteoarthritis patients before and after surgery. It was hypothesized that pain rather than knee joint mobility affects the coordination between balance and movement control. The experiment was performed with 25 adult individuals. Eleven were osteoarthritic patients with damage restricted to one lower limb (8 right leg and 3 left leg). Subjects were recruited within two weeks before total knee replacement by the same orthopedic surgeon using the same prosthesis and technics of surgery. Osteoarthritic patients were tested before total knee replacement (pre-surgery session) and then, 9 of the 11 patients were tested one year after the surgery when re-educative training was completed (post-surgery session). 14 adult individuals (men: n = 7 and women: n = 7) were tested as the control group. The way in which the center of mass shift forward and toward the supporting side is initiated (timing and amplitude) did not vary within patients before and after surgery. In addition knee joint range of motion of the leading leg remained close to normal before and after surgery. However, the relative timing between both postural and movement phases was modified for the osteoarthritis supporting leg (unusual strategy for stepping-down) before surgery. The "coordinated" control of balance and movement turned to be a "sequential" mode of control; once the body weight transfer has been completed, the movement onset is triggered. This strategy could be aimed at shortening the duration-time supporting on the painful limb. However no such compensatory response was observed. The change in the strategy used when supporting on the arthritis and painful limb could result from the action of nociceptors that lead to increased proprioceptor thresholds, thus gating the proprioceptive inputs that may be the critical afferents in controlling the timing of the coordination between balance and movement initiation control.


Excitation profile of surface-enhanced Raman scattering in graphene-metal nanoparticle based derivatives.
Understanding energy transfer mechanisms in graphene derivatives is strongly motivated by the unusually interesting electronic properties of graphene, which can provide a template for the creation of novel nanostructured derivatives. From a synthetic point of view, it is highly attractive to envision being able to synthesize pristine graphene from precursors such as graphene oxide (GO). While this goal may be challenging over large length-scales, it is possible to generate regions of graphene at the nanoscale, confirmed by Raman spectroscopy or other methods. We describe an in situ method of nucleating gold or palladium nanoparticles in the presence of ethylene glycol as a reducing agent, while simultaneously reducing GO to graphene. The Au nanoparticles aid in spectroscopic characterization by both quenching fluorescence, allowing the graphene D and G bands to be quantified, and yielding a surface enhancement of about two orders of magnitude. We observe the excitation profile (488-785 nm) of the surface enhanced Raman spectrum (SERS) of graphene with Au nanoparticles adsorbed on the surface. Both the D and G bands display a resonance at approximately 593 nm (2.09 eV). This resonance may be interpreted as a combination of the plasmon resonance at 548 nm and a likely contribution from charge transfer as well. In addition, we observe a stiffening of the G band compared with that of graphene. The mechanism of the SERS, whether plasmonic or charge transfer-based, enables insight into the electronic pathways available to the graphene-nanoparticle system. We discuss our results in the context of several existing studies of graphene-based nanostructure derivatives.


Glaucoma after cataract extraction and posterior chamber lens implantation in children.
To evaluate the incidence of postoperative glaucoma in children who have cataract extraction and posterior chamber intraocular lens (IOL) implantation. Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA. The incidence of glaucoma of all etiologies was evaluated in 45 eyes of 37 selected consecutive patients aged 1 to 18 years who had cataract extraction and posterior chamber IOL implantation from 1991 to 1994. Mean follow-up was 23 months (range 6 to 38 months). Nineteen patients had traumatic and 18 had developmental cataract. Exclusion criteria were microcornea smaller than 9.0 mm in diameter, preoperative glaucoma, or poor pupil dilation. The surgical technique comprised a continuous curvilinear anterior capsulorhexis in most cases, extracapsular aspiration by Ocutome or phacoemulsification, and retention of the posterior capsule. A peripheral iridectomy was done in 7 eyes (16%). Postoperative medications included topical atropine combined with topical, subconjunctival, and systemic corticosteroids and antibiotics. Three patients with traumatic cataract developed postoperative glaucoma during the follow-up. One developed pseudophakic pupillary block; however, a peripheral iridectomy prevented glaucoma. Two other patients developed late-onset glaucoma: one secondary to angle recession and the other to peripheral anterior synechias. No patient with developmental cataract developed glaucoma. Careful patient selection, atraumatic surgical technique, continuous curvilinear capsulorhexis, in-the-bag IOL placement, postoperative atropine, and topical and systemic corticosteroids significantly lower the incidence of pseudophakic pupillary block and glaucoma. Although no patient developed glaucoma, lifelong follow-up is mandatory to detect chronic open-angle and traumatic angle-recession glaucoma.


Prevalence, associated factors, awareness, treatment, and control of hypertension: Findings from a cross sectional study conducted as a part of a community based intervention trial in Surkhet, Mid-western region of Nepal.
Hypertension is one of the leading public health problems globally. About half of the deaths from cardiovascular diseases were attributed to hypertension in 2008. Reduction of blood pressure to normal range is one of the major challenges in preventing complications and future burden of cardiovascular diseases. Therefore, this study aims to determine prevalence, awareness, treatment and control of hypertension and its associated factors in Nepal. This was a community based cross-sectional study conducted as a part of a community based intervention trial in Birendranagar Municipality of Surkhet district located at the Mid-western region of Nepal. We enrolled 1159 subjects aged 30 years and above. Out of 12 wards (administrative unit), four wards were selected randomly. Three hundred participants were recruited from each selected ward. Trained enumerator collected socio-demographic, anthropometric, and clinical data using standard STEPS questionnaires. Out of all participants, women were 71% and mean age was 47±12.6 years. The overall prevalence of hypertension was 38.9% (95% CI: 36-41.7) while age and sex adjusted prevalence was 40.6%. The hypertension was present in 48.1% (95% CI: 45.2-50.9) of men and 35.2% (95% CI: 32.4-37.9)] of women. Male gender (OR = 1.49), older age (OR = 1.04 per year), Dalit caste (OR = 1.71), past history of cigarettes smoking (OR = 2.78), current alcohol consumption (OR = 1.75), and raised body mass index (OR = 1.17 per unit) were identified as significant factors associated with hypertension. Of total hypertensive respondents, 53.4% (95% CI: 48.7-58) were aware, 29% (95% CI: 24.8-33.1) were receiving treatment for high blood pressure, and 8.2% (95% CI: 5.6-10.7) had controlled blood pressure. The awareness, treatment, and control status were worse in younger participants. The study revealed high prevalence with low awareness, treatment, and control of hypertension in Nepal. Gender, age, ethnicity, smoking, drinking alcohol, and body mass index were associated with hypertension. Immediate public health and individual measures are warranted to reduce future burden of cardiovascular diseases. ClinicalTrial.gov (NCT02981251).


The Affordable Care Act's Missing Consensus: Values, Attitudes, and Experiences Associated with Competing Health Reform Preferences.
Ten years after its enactment, public support for the Affordable Care Act (ACA) still only reaches a scant majority. Candidates for the presidency-and the sitting president-have endorsed health reforms that would radically transition US health care away from the current system upon which the ACA was built. Few opinion surveys to date have captured dominant preferences among alternative health reform policies or characterized attitudes and experiences that might be associated with policy preferences. Using a 2019 nationally representative telephone survey, this article considers how variations in political values, attitudes toward government, and experiences with the health care system relate to competing health reform preferences. Differences between those who favor Medicare for All over building on the ACA largely reflect different levels of satisfaction with the status quo and views of private health insurance. By contrast, differences between ACA supporters and those who would favor replacing it with a state-based alternative reflect sharply different political values and attitudes. Key differences remain significant after controlling for demographic, health, and political characteristics. Overwhelming public support still eludes the ACA, and reaching consensus on future directions for health reform will remain challenging given differences in underlying beliefs.


Genetic engineering of Escherichia coli inorganic pyrophosphatase. Tyr55 and Tyr141 are important for the structural integrity.
Two tyrosines are supposed to be essential for the activity and to participate in the stabilization of Escherichia coli inorganic pyrophosphatase (PPiase) against heat denaturation [Samejima, T., Tamagawa, Y., Kondo, Y., Hachimori, A., Kaji, H., Takeda, A. and Shiroya, Y. (1988) J. Biochem. (Tokyo) 103, 766-772]. To locate these two tyrosines in the amino acid sequence, we substituted all the eight tyrosines of E. coli PPiase with phenylalanine and studied the properties of these YF mutant PPiases. Interestingly, substitution of the tyrosines (Tyr51, Tyr55 and Tyr141) conserved with the amino acid sequence of yeast PPiase [Lahti, R., Kolakowski, L. F., Heinonen, J., Vihinen, M., Pohjanoksa, K. and Cooperman, B. (1990) Biochim. Biophys. Acta 1038, 338-345] exerted the most drastic effects on the structure and activity of E. coli PPiase. PPiase variants YF51, YF55 and YF141 had 64%, 7% and 22% of the wild-type PPiase activity, respectively. Furthermore, PPiase variant YF141 had an increased sensitivity to heat denaturation, whereas mutant PPiase YF55 displayed a profound conformational change, as demonstrated by the binding of the fluorescent dye 9-(diethylamino)-5H-benzo(alpha) phenoxazine-5-one (Nile red) that monitors the hydrophobicity of protein surfaces. None of the tyrosines of E. coli PPiase seem to be essential for catalysis, but Tyr55 and Tyr141 are important for the structural integrity of E. coli PPiase.


Association of Occupational Exposure to Inhaled Agents in Operating Rooms With Incidence of Chronic Obstructive Pulmonary Disease Among US Female Nurses.
Employment in operating rooms (ORs) may involve exposure to several inhaled agents, including surgical smoke and disinfectants, which are associated with adverse respiratory health effects. However, the association of long-term employment in ORs and chronic obstructive pulmonary disease (COPD) remains unknown. To examine the association of working in an OR with incidence of COPD among female nurses in the US. This cohort study used data from the Nurses' Health Study for US female registered nurses who provided information on questionnaires regarding OR employment history in 1984 and job type in 1982 and who had no history of COPD in 1984 (baseline). Data analyses were conducted from April 1, 2020, to January 31, 2021. Duration of nursing in the OR and job type. The associations of any employment as an OR nurse, duration of employment, and duration and job type with incidence of self-reported, physician-diagnosed COPD. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models stratified by age and calendar year. Models were adjusted for covariates, with model 1 adjusting for age, model 2 also adjusting for cigarette smoking status and pack-year of smoking, and model 3 also adjusting for race and ethnicity, US Census region, and body mass index. Among 75 011 female nurses included in the analyses, the mean (SD) age at baseline was 50.5 (7.2) years; 29% had a history of employment in an OR, and 3% had 15 or more years of OR experience. In model 3, employment in an OR for 15 or more years was associated with a 46% increased risk of developing COPD compared with no history of OR employment (HR, 1.46; 95% CI, 1.10-1.93). Compared with nurses who never worked in an OR and had an administrative or nursing education function or a nonnursing job in 1982, the risk of developing COPD was greater among nurses who provided outpatient care (HR, 1.24; 95% CI, 1.04-1.47) and nurses employed in inpatient units (HR, 1.31; 95% CI, 1.07-1.59) who had no history of OR employment and was 69% greater among nurses with OR experience of 15 years or more (HR, 1.69; 95% CI, 1.25-2.28). In this cohort study, OR employment of 15 years or more was associated with an increased risk of developing COPD among female nurses. Additional studies with more recent and direct environmental monitoring data of multiple occupational exposures are needed to assess the relative role of exposure to surgical smoke and disinfectants in the observed association.


Determinants of skeletal muscle contributions from circulating cells, bone marrow cells, and hematopoietic stem cells.
To investigate the factors that regulate incorporation into uninjured or damaged skeletal muscle of donor markers derived from unfractionated bone marrow (BM) cells or from highly purified c-kit+ Thy1.1lo Lin- Sca-1+ hematopoietic stem cells (HSCs), we evaluated myofiber chimerism of multiple muscle groups in irradiated and transplanted recipient mice and in unirradiated parabiotic animals. Uninjured panniculus carnosus, diaphragm, and abdominal muscles infrequently incorporated donor markers into myofibers in a subset of animals after either BM or HSC transplantation; however, acute muscle injury was essential to elicit contributions to triceps surae (TS) and tibialis anterior muscles. The low level of incorporation of donor marker-expressing myofibers could not be enhanced either by transplantation into newborn recipients or by induced migration of HSCs into the periphery. Analysis of muscle chimerism in unirradiated animals joined surgically by parabiosis revealed that contributions of circulating cells to myofibers in the TS were injury dependent and that at least some circulating cells with the potential to contribute to regenerating muscle derive from BM, suggesting that hematoablative preconditioning is not required for such contributions. In all cases tested, donor-derived myofibers expressed both donor-specific and host-specific markers, suggesting that they arise by low-level fusion into skeletal muscle of cells that can include the progeny of HSCs. It is not yet clear whether such events represent a normal myogenic pathway or a pathological response to muscle damage.


Earwax Impaction: Symptoms, Predisposing Factors and Perception among Nigerians.
Earwax impaction is a common ear disorder with presentation worldwide. This study aimed at determining the clinical presentation, patients' perception of earwax, and its predisposing factors among Nigerians. This prospective study was conducted on consented patients with diagnosis of earwax impaction at the Ear, Nose, and Throat Clinic of the University Teaching Hospital, Ado Ekiti, Ekiti state, south west, Nigeria. The research was carried out over a period of one year (April 2008 and March 2009). All consented patients were told about the aim and scope of the study and their biodata were taken. Detailed history of the presenting complaints and otological complaints were taken and all data entered into structured questionnaires. Full-ear examination and otoscopy were performed and our findings were documented. From all these exercise, data obtained were collated and statistically analyzed. A total of 437 patients were diagnosed with earwax impaction and prevalence of 20.1% was found. There was 52.2% male preponderance with male to female ratio of 1:1. Bimodal peak age distribution of patients was found at the extreme ages of life. Most common sources of our patients referrals were 39.6% general medical practitioners with least from 6.2% self-reporting. Common presentations were 277 (63.3%) hearing loss, 268 (61.3%) earache (otalgia), and 234 (53.5%) tiinitus. Unilateral earwax impaction, 75.1% was more common than bilateral earwax impaction. Right ear was more affected than left ear. Recurrent earwax impaction of 66.1% was found in our study. About 382 (87.4%) believed earwax was due to dirt or dust. Most common predisposing factors among our patients were self-ear cleaning. Common predisposing factor of this high recurrent earwax impaction were wrong perception and preventable self-ear cleaning with indiscriminate objects including cotton tip swab. This condition could be reduced by health education of the community.


Declines in nonwhite and white neonatal mortality in Mississippi, 1975-80.
Linked birth and death records provided the population for an investigation of declines in nonwhite and white neonatal mortality rates (NMR) in Mississippi between 1975 and 1980. The effect of changes in the characteristics of women giving birth and in perinatal care on declining NMRs was analyzed. A decomposition of the difference in the 1975-76 and 1979-80 NMRs was performed to determine whether declines in NMRs were due to shifts in population characteristics or in characteristic-specific rates. Between 1975 and 1980, the NMR declined significantly by 1 death per 1,000 live births per year among nonwhites and by 0.8 per 1,000 among whites. Increases in the number of prenatal visits during the study period were associated with part of this decline, especially for nonwhites. The effect of rising use of prenatal care on NMRs was not, however, a result of shifts in the birth weight distribution. The decrease in NMRs was also associated with declining birth weight-specific rates; 75 percent of the decrease in rates was noted among low birth weight infants. Shifts in the distribution of birth weight and in maternal characteristics had little effect on declining NMRs. A strong commitment of the Mississippi State Board of Health to provide prenatal care to indigent women may be responsible for the large increases in use of prenatal care among Mississippi women. The decline in NMRs among low birth weight infants is likely linked to greater availability of specialized care for the sick neonate, although survival of these infants increased across the State, even where specialized care was not available.


Differential Purkinje cell simple spike activity and pausing behavior related to cerebellar modules.
The massive computational capacity of the cerebellar cortex is conveyed by Purkinje cells onto cerebellar and vestibular nuclei neurons through their GABAergic, inhibitory output. This implies that pauses in Purkinje cell simple spike activity are potentially instrumental in cerebellar information processing, but their occurrence and extent are still heavily debated. The cerebellar cortex, although often treated as such, is not homogeneous. Cerebellar modules with distinct anatomical connectivity and gene expression have been described, and Purkinje cells in these modules also differ in firing rate of simple and complex spikes. In this study we systematically correlate, in awake mice, the pausing in simple spike activity of Purkinje cells recorded throughout the entire cerebellum, with their location in terms of lobule, transverse zone, and zebrin-identified cerebellar module. A subset of Purkinje cells displayed long (>500-ms) pauses, but we found that their occurrence correlated with tissue damage and lower temperature. In contrast to long pauses, short pauses (<500 ms) and the shape of the interspike interval (ISI) distributions can differ between Purkinje cells of different lobules and cerebellar modules. In fact, the ISI distributions can differ both between and within populations of Purkinje cells with the same zebrin identity, and these differences are at least in part caused by differential synaptic inputs. Our results suggest that long pauses are rare but that there are differences related to shorter intersimple spike intervals between and within specific subsets of Purkinje cells, indicating a potential further segregation in the activity of cerebellar Purkinje cells.


Regulation of hypoxia-inducible genes by PGC-1 alpha.
Atmospheric oxygen appeared approximately 2.3 billion years ago and sustains most complex life on earth. As mitochondria evolved to harness the energy in oxygen, systems developed to sense and respond to local oxygen concentrations and metabolic conditions. For more than a decade, research has focused on hypoxia-inducible factor 1 (HIF1), a key component of the eukaryotic oxygen-response system. Recently, evidence for other systems has also surfaced. One of these systems involves the PGC-1 alpha coactivator, a powerful transcriptional regulator of mitochondria and oxidative metabolic programs. This brief review will focus on this burgeoning role for PGC-1 alpha and will highlight the many questions that remain unanswered.


Gastric adenocarcinoma with prostatic metastasis.
Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare. Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with prostatic metastasis diagnosed through the analysis of biopsy specimens from representative lesions in the stomach and prostate gland. Immunohistochemistry of the prostatic tissue showed positive staining for cytokeratin 7 and negative staining for prostate-specific antigen (PSA), whereas the serum PSA level was normal, confirming the diagnosis of prostatic metastasis from carcinoma of the stomach.


One-stage operation for male transsexuals.
A simplified surgical technique for a male-to-female transsexual operation has been developed and applied satisfactorily in a series of carefully selected patients. The simplicity of the technique allows relatively brief hospitalization for 1-stage sex conversion, provides satisfactory cosmetic and functional results, and has not been accompanied by any untoward complications.


A case of vivax malaria complicated by adult respiratory distress syndrome and successful management with extracorporeal membrane oxygenation.
Complicated malaria is mainly caused by Plasmodium falciparum, but, increasingly, Plasmodium vivax is also being reported as a cause. Since the reemergence of indigenous vivax malaria in 1993, cases of severe malaria have been steadily reported in Korea. Herein, we report a case of vivax malaria complicated by adult respiratory distress syndrome (ARDS) that was successfully managed with extracorporeal membrane oxygenation (ECMO). A 59-year-old man presented at our hospital with fever and abdominal pain, which had persisted for 10 days. On admission, the patient had impaired consciousness, shock, hypoxia and haziness in both lungs, jaundice, thrombocytopenia and disseminated intravascular coagulation, metabolic acidosis, and acute kidney injury. A peripheral blood smear and a rapid diagnostic test verified P. vivax mono-infection. Ten hours after admission, hypoxia became more severe, despite providing maximal ventilatory support. The administration of antimalarial agents, ECMO, and continuous venovenous hemofiltration resulted in an improvement of his vital signs and laboratory findings. He was discharged from the hospital 7 weeks later, without any sequelae.


Specificity of the Relationships Between Dysphoria and Related Constructs in an Outpatient Sample.
Dysphoria has recently been conceptualized as a complex emotional state that consists of discontent and/or unhappiness and a predominantly externalizing mode of coping with these feelings. The Nepean Dysphoria Scale (NDS) was developed on the basis of this model of dysphoria and used in this clinical study to ascertain the specificity of the relationships between dysphoria and relevant domains of psychopathology. Ninety-six outpatients completed the NDS, Symptom Checklist 90-Revised (SCL-90R) and Depression, Anxiety, Stress Scales, 21-item version (DASS-21). The scores on the NDS subscales (Discontent, Surrender, Irritability and Interpersonal Resentment) and total NDS scores correlated significantly with scores on the DASS-21 scales and relevant SCL-90R subscales. Multiple regression analyses demonstrated the following: DASS-21 Depression and Stress each had unique relationships with NDS Discontent and Surrender; DASS-21 Anxiety had a unique relationship with NDS Discontent; SCL-90R Hostility and Paranoid Ideation and DASS-21 Stress each had unique relationships with NDS Irritability; and SCL-90R Paranoid Ideation and DASS-21 Stress, Depression and Anxiety each had unique relationships with NDS Interpersonal Resentment. These findings support the notion that dysphoria is a complex emotional state, with both non-specific and specific relationships with irritability, tension, depression, paranoid tendencies, anxiety, hostility and interpersonal sensitivity. Conceptual rigor when referring to dysphoria should be promoted in both clinical practice and further research.


Itinerary profiling to analyze a large number of protein-folding trajectories.
Understanding how proteins fold through a vast number of unfolded states is a major subject in the study of protein folding. Herein, we present itinerary profiling as a simple method to analyze molecular dynamics trajectories, and apply this method to Trp-cage. In itinerary profiling, structural clusters included in a trajectory are represented by a bit sequence, and a number of trajectories, as well as the structural clusters, can be compared and classified. As a consequence, the structural clusters that characterize the foldability of trajectories were able to be identified. The connections between the clusters were then illustrated as a network and the structural features of the clusters were examined. We found that in the true folding funnel, Trp-cage formed a left-handed main-chain topology and the Trp6 side-chain was located at the front of the main-chain ring, even in the initial unfolded states. In contrast, in the false folding funnel of the pseudo-native states, in which the Trp6 side-chain is upside down in the protein core, Trp-cage had a right-handed main-chain topology and the Trp side-chain was at the back. The initial topological partition, as determined by the main-chain handedness and the location of the Trp residue, predetermines Trp-cage foldability and the destination of the trajectory to the native state or the pseudo-native states.


The safety and efficacy of ramucirumab in combination with paclitaxel for the treatment of advanced gastric or gastro-esophageal junction adenocarcinoma.
Gastric cancer (GC) is a health problem. Platinum and fluoropyrimidine-based combinations have been established as first-line drugs used worldwide. However, there are no other options for treatment if first-line therapy fails. Therefore, second-line treatment options are needed. Targeted therapies have optimized the results of chemotherapy, specifically trastuzumab as a first-line and ramucirumab in second-line. Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) are involved in the pathogenesis of GC. Clinical studies have evaluated VEGFR-2 blocked in second line. Two phase III trials using ramucirumab alone or associated to paclitaxel have demonstrated that second-line therapy could improve the survival of patients with GC. Expert commentary: VEGF-2 receptor blockade is effective at treating GC. The combination of paclitaxel with ramucirumab can be used to establish an angiogenic blockade in second-line therapy. The magnitude of the treatment effect suggests that this combination should be used as the current standard.


Fetal Cystoscopy and Vesicoamniotic Shunting in Lower Urinary Tract Obstruction: Long-Term Outcome and Current Technical Limitations.
In utero therapeutic approaches for lower urinary tract obstruction (LUTO) have been developed to salvage the fetal kidney function. The aim of this work was to report the long-term survival, nephrological, and urological outcome of children treated prenatally for LUTO using operative fetal cystoscopy (FC) and vesicoamniotic shunting (VAS) or both. A retrospective study of 48 procedures (23 FC, 25 VAS) was performed on 33 patients (between 2008 and 2018). Reviewed data included prenatal management and clinical follow-up by a pediatric nephrologist and a pediatric urologist. Both intention-to-treat and per-protocol analyses were conducted. The median follow-up was 3.6 years (0.5-7) for FC and 2.5 years (1.1-5.1) for VAS. There was no difference between FC and VAS in terms of survival (92 vs. 83%, p = 1), complication rate (74 vs. 92%, p = 0.88), or chronic kidney disease (58 vs. 50%, p = 1). The number of procedures was higher in the VAS group: 1.7 (1-3) versus 1.1 (1-2), p = 0.01. With a 30% rate of technical failure, FC added diagnostic value in 3 out of 21 cases. No difference was found between FC and VAS regarding survival, long-term kidney function, or urological outcome. Despite overly optimistic reports on FC, it lacks reproducibility due to posterior-urethra inadequate visualization and inappropriate instrumentation.


CD19+CD24hiCD38hi B Cell Dysfunction in Primary Biliary Cholangitis.
CD19+CD24hiCD38hi B cells are immature transitional B cells that, in normal individuals, exert suppressive effects by IL-10 production but are quantitatively altered and/or functionally impaired in individuals with various autoimmune diseases. Primary biliary cholangitis (PBC), an autoimmune disease, clinically presents as chronic cholestasis and nonsuppurative destructive cholangitis. A role for CD19+CD24hiCD38hi B cells in PBC is unknown. This study investigated the frequency and functional variation of circulating CD19+CD24hiCD38hi B cells in PBC patients. Flow cytometry was employed to quantify the percentage of CD19+CD24hiCD38hi B cells in peripheral blood samples. Correlations between CD19+CD24hiCD38hi B cells and routine laboratory parameters were assessed. Levels of IL-10, TNF-α, IL-6 and IL-12, and Tim-1 in CD19+CD24hiCD38hi B cells from PBC patients were analyzed. The effect of CD19+CD24hiCD38hi B cells on CD4+T cell differentiation was evaluated. The percentage of CD19+CD24hiCD38hi B cells in PBC patients was significantly higher than in healthy controls and was positively correlated with liver cholestasis. After activation by anti-B cell receptor and CpG, the production of IL-10 was decreased and the production of IL-6 and IL-12 was increased in CD19+CD24hiCD38hi B cells from PBC patients. Moreover, Tim-1 levels were significantly downregulated in CD19+CD24hiCD38hi B cells from PBC patients. Coculture showed that PBC-derived CD19+CD24hiCD38hi B cells were less capable of CD4+T cell inhibition, but promoted Th1 cell differentiation. In conclusion, PBC patients have expanded percentages, but impaired CD19+CD24hiCD38hi B cells, which correlate with disease damage. In PBC patients, this B cell subset has a skewed proinflammatory cytokine profile and a decreased capacity to suppress immune function, which may contribute to the pathogenesis of PBC.


[Consequences of specific prevention on the diagnosis of Pneumocystis carinii pneumonia in patients with HIV infection. Comité SIDA de l'Hôpital Saint-Antoine].
In a prospective study the authors compared the clinical, radiological, biochemical and diagnostic features of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients who were or were not receiving a specific prophylactic treatment. The study included 386 patients with suspected PCP, 201 of whom were under specific prophylactic therapy. Induced expectoration and/or bronchoalveolar lavage provided a diagnosis of PCP in 89 patients, 21 of whom were under specific prophylaxis. Apart from a number of circulating CD4 lymphocytes that was significantly lower in the patients under prophylaxis, there was no significant difference between the two groups. Thus, being under specific prophylaxis should have no effect on the diagnosis of PCP in HIV-infected patients.


Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical considerations.
Opioid-induced hyperalgesia (OIH) is most broadly defined as a state of nociceptive sensitization caused by exposure to opioids. The state is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain may actually become more sensitive to certain painful stimuli. The type of pain experienced may or may not be different from the original underlying painful condition. Although the precise molecular mechanism is not yet understood, it is generally thought to result from neuroplastic changes in the peripheral and central nervous systems that lead to sensitization of pronociceptive pathways. OIH seems to be a distinct, definable, and characteristic phenomenon that may explain loss of opioid efficacy in some cases. Clinicians should suspect expression of OIH when opioid treatment effect seems to wane in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia unassociated with the pain as previously observed. This review highlights the important mechanistic underpinnings and clinical ramifications of OIH and discusses future research directions and the latest clinical evidence for modulation of this potentially troublesome clinical phenomenon.


Incidence and prognosis of meningitis due to Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis in Sweden.
The incidence, concomitant conditions and case fatality rate of Haemophilus influenzae (Hi) and pneumococcal meningitis and of invasive meningococcal infections were studied retrospectively in Sweden (population 8.4 million) for the years 1987-89, the period before vaccination against Hi type b started. A total of 1,019 cases with culture-verified infection were found. The incidence rates per 100,000 per year were 1.8 for Hi meningitis, 1.2 for pneumococcal meningitis and 1.0 for invasive meningococcal infections. The age-specific incidence was highest in the 3-23 months age group for the 3 bacterial species. Pneumococcal meningitis was common in individuals > or = 60 years and meningococcal infections in the age-group 10-24 years. A serious concomitant condition was known in 57% of all patients with pneumococcal meningitis while this was uncommon for the other organisms. The case fatality rate was 2% for Hi meningitis, 24% for pneumococcal meningitis and 10% for meningococcal infections. All 81 pneumococcal isolates which had been serotyped belonged to serotypes in the 23-valent pneumococcal vaccine. Of the meningococcal isolates, 65% belonged to serogroup B. In conclusion, the high incidence of Hib meningitis justifies general Hib vaccination. Development of a vaccine against N. meningitidis group B should have high priority. Furthermore, improved pneumococcal vaccines are needed for patients with predisposing conditions. The currently available pneumococcal polysaccharide vaccine seems to be underused.


Transcriptional alteration of NF-κB-associated long noncoding RNAs in the stomach of Helicobacter pylori-infected and non-infected patients.
Helicobacter pylori could colonize the gastric mucosa and cause gastritis, ulcers and cancer. Numerous virulence factors have been identified in this bacterium that play important roles in promoting gastric disorders. Although the interaction of long noncoding RNAs (lncRNAs) with transcription, processing, and translation of genes associated with different diseases are described, their interaction with the inflammatory genes and H. pylori infection in the gastric tissue is not well known. This study compared changes in common NF-κB-regulatory lncRNAs in the gastric tissue of H. pylori-infected and non-infected patients with gastritis. Moreover, a link between the virulence entity of the strains and the transcriptional changes was analyzed. Two groups of infected and non-infected patients with chronic gastritis were included in the study. Genotyping of the H. pylori strains was done by PCR and relative changes in the expression of NF-κB and regulatory lncRNAs, lincRNA-p21, MALAT1, NKILA, were measured by relative quantitative real time-PCR. Transcriptional levels of MALAT1, lincRNA-p21, and NKILA genes decreased in the infected patients compared with the non-infected patients, which was significantly linked with increased NF-κB gene expression. Our results showed that a hypervirulent strain of H. pylori with oipA"on"/HP-NAP+/iceA1+/iceA2+/vacA s1m1/s1m2+/cagA+ genotype can promote a higher level of NF-κB transcription in the inflamed tissue. H. pylori infection could promote down-regulation of lincRNA-p21, MALAT1 and NKILA in the infected gastric tissue in correlation with NF-κB upregulation. More detailed studies are needed to show a link between the virulence genes and their impact on the regulation of lncRNAs in the stomach.


Endoscopic therapeutic esophageal interventions: something old, something new, something to be established.
Endoscopic esophageal interventions are an exciting topic because indications for the use of both the available devices and the new devices continue to evolve. This article reviews the most notable developments and the results of endoscopic esophageal therapeutic interventions published in 2003. In 2003, three follow-up series on photodynamic therapy were published. Photodynamic therapy was shown to improve dysphagia from esophageal cancer, but comparative studies with other techniques are needed. Photodynamic therapy was also effective in removing Barrett epithelium. Of concern is that patients with residual Barrett esophagus after ablative treatment are still at an increased risk for esophageal cancer. Endoscopic mucosal resection has become an accepted alternative for surgical resection of early-stage esophageal cancer, with increasing evidence that lesions larger than 20 mm can be safely removed by this technique. Completely covered plastic self-expanding stents have been demonstrated to reduce recurrent dysphagia by the ingrowth or overgrowth of nonmalignant tissue. A new indication for self-expanding metal stents is the treatment of traumatic nonmalignant perforations of the esophagus. Stents are also increasingly used for strictures refractory to repeated dilations and as an alternative to pneumatic dilation in achalasia. Bleeding esophageal varices can safely be treated with vasoactive drugs, which is good news for endoscopists who value a good night's rest. Various follow-up studies of endoscopic antireflux procedures were published that suggested good symptomatic results. However, with respect to the reduction of acid exposure to the esophagus, these data were less impressive. In 2003, much additional data about current techniques became available. In addition, new indications for existing devices were developed. Finally, for some techniques more information will be needed before their exact role can be established.


Speech and Language Therapists' Perspectives of an E-Learning Course on Providing Feedback in the Clinical Learning Environment.
A fundamental component of supervising a student speech and language therapist (SLT) on placement is the provision of feedback. There are numerous identified challenges to ensure the delivery of high-quality feedback to optimise student learning and student success. Supervisors can help overcome these challenges and engage in evidence-based feedback processes if they are supported to develop the necessary knowledge and skills. E-learning is one possible means to provide this professional development to a large number of practising SLTs who are geographically dispersed and have conflicting schedules. This study aimed to capture and evaluate the perspectives of SLTs who completed an e-learning course on providing feedback in the clinical learning environment, including the suitability and effectiveness of the e-learning tool used. An innovative e-learning course was designed to provide asynchronous video and interactive content on evidence-based theories and practices for effective feedback processes. Clinical scenarios relevant to the discipline of speech and language therapy were included. Participants were invited to complete optional, anonymous pre- and post-evaluation surveys. Data were analysed quantitively (descriptive and inferential statistics) and qualitatively (thematic analysis). Participants indicated that the e-learning course supported them to enhance their feedback processes in the clinical learning environment through identified changes to their practices. The increases in confidence providing feedback they reported were statistically significant. In addition, the e-learning course was rated highly on numerous variables related to quality. Recommendations for adaptations and additions were also highlighted. An e-learning course on effective and evidence-based feedback processes provides an opportunity to provide professional development to a large number of geographically dispersed practitioners in a cost-effective and flexible way. This could ensure more SLTs are confident and competent in their role as supervisor of students, which requires distinct knowledge and skills from that of a practitioner. Ultimately, this will help maximise educator and student success in the feedback process and consequently improve clinical performance and healthcare delivery.


Economic model for emergency use authorization of intravenous peramivir.
To develop 3 computer simulation models to determine the potential economic effect of using intravenous (IV) antiviral agents to treat hospitalized patients with influenza-like illness, as well as different testing and treatment strategies. Stochastic decision analytic computer simulation model. During the 2009 influenza A(H1N1) pandemic, the Food and Drug Administration granted emergency use authorization of IV neuraminidase inhibitors for hospitalized patients with influenza, creating a need for rapid decision analyses to help guide use. We compared the economic value from the societal and third-party payer perspectives of the following 4 strategies for a patient hospitalized with influenza-like illness and unable to take oral antiviral agents: Strategy 1: Administration of IV antiviral agents without polymerase chain reaction influenza testing. Strategy 2: Initiation of IV antiviral treatment, followed by polymerase chain reaction testing to determine whether the treatment should be continued. Strategy 3: Performance of polymerase chain reaction testing, followed by initiation of IV antiviral treatment if the test results are positive. Strategy 4: Administration of no IV antiviral agents. Sensitivity analyses varied the probability of having influenza (baseline, 10%; range, 10%-30%), IV antiviral efficacy (baseline, oral oseltamivir phosphate; range, 25%-75%), IV antiviral daily cost (range, $20-$1000), IV antiviral reduction of illness duration (baseline, 1 day; range, 1-2 days), and ventilated vs nonventilated status of the patient. When the cost of IV antiviral agents was no more than $500 per day, the incremental cost-effectiveness ratio for most of the IV antiviral treatment strategies was less than $10,000 per quality-adjusted life-year compared with no treatment. When the cost was no more than $100 per day, all 3 IV antiviral strategies were even more cost-effective. The order of cost-effectiveness from most to least was strategies 3, 1, and 2. The findings were robust to changing risk of influenza, influenza mortality, IV antiviral efficacy, IV antiviral daily cost, IV antiviral reduction of illness duration, and ventilated vs nonventilated status of the patient for both societal and third-party payer perspectives. Our study supports the use of IV antiviral treatment for hospitalized patients with influenza-like illness.


Identification of abnormal motor cortex activation patterns in children with cerebral palsy by functional near-infrared spectroscopy.
We demonstrate the utility of functional near-infrared spectroscopy (fNIRS) as a tool for physicians to study cortical plasticity in children with cerebral palsy (CP). Motor cortex activation patterns were studied in five healthy children and five children with CP (8.4+/-2.3 years old in both groups) performing a finger-tapping protocol. Spatial (distance from center and area difference) and temporal (duration and time-to-peak) image metrics are proposed as potential biomarkers for differentiating abnormal cortical activation in children with CP from healthy pediatric controls. In addition, a similarity image-analysis concept is presented that unveils areas that have similar activation patterns as that of the maximum activation area, but are not discernible by visual inspection of standard activation images. Metrics derived from the images presenting areas of similarity are shown to be sensitive identifiers of abnormal activation patterns in children with CP. Importantly, the proposed similarity concept and related metrics may be applicable to other studies for the identification of cortical activation patterns by fNIRS.


The first patient with locally acquired dengue fever in Hong Kong.
This report is of the first locally acquired case of dengue fever. The diagnosis was made even in the absence of a history of travel outside Hong Kong. The patient was a 21-year-old man, who presented with high fever, leukopenia, thrombocytopenia, and elevated liver enzymes. His haematocrit revealed mild haemoconcentration but the albumin was normal throughout the course of the illness. His blood pressure remained low with no tachycardia or overt shock syndrome. The pyrexia subsided 4 days after admission to hospital and all haematological and biochemical abnormalities eventually normalised. The pathogenesis, diagnostic criteria of dengue haemorrhagic fever and dengue shock syndrome, and control of dengue infection are discussed.


Topical treatment with inhibitors of the phosphatidylinositol 3'-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways reduces melanoma development in severe combined immunodeficient mice.
Topical treatment with inhibitors of the phosphatidylinositol 3'-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways inhibited the growth of TPras transgenic melanomas in severe combined immunodeficient mice, blocked invasive behavior, and reduced angiogenesis. The inhibitor Ly294002, which is specific for phosphatidylinositol 3'-kinase, effectively reduced melanoma cell growth both in vitro and in vivo. Both Ly294002 and U0126, a mitogen-activated protein kinase kinase 1/2 inhibitor, reduced invasion, which correlated with reduction of the metalloproteinase matrix metalloproteinase 2. Tumor angiogenesis was disrupted through inhibition of vascular endothelial growth factor production from the tumor cells and antiangiogenic effects on endothelial cells. Observations with TPras melanoma cells that express dominant negative Deltap85 or kinase-inactive Raf(301) supported the specificity of the phenomena observed with the chemical inhibitors. These studies demonstrate that topical treatment targeting Ras effectors is efficacious, without systemic toxicities, and may prove to be useful in treating and preventing the progression of cutaneous melanoma.


Inhibition of T cell activation by pharmacologic disruption of the MEK1/ERK MAP kinase or calcineurin signaling pathways results in differential modulation of cytokine production.
Productive T cell activation leading to cytokine secretion requires the cooperation of multiple signaling pathways coupled to the TCR and to costimulatory molecules such as CD28. Here, we utilized two pharmacophores, PD98059 and FK506, that inhibit, respectively, mitogen-activated protein (MAP) kinase kinase 1 (MEK 1) and calcineurin, to determine the relative role of the signaling pathways controlled by these enzymes in T cell activation. Although the two compounds had distinctive effects on CD69 induction, they both suppressed T cell proliferation induced by anti-CD3 mAb, in a manner reversible by exogenous IL-2, suggesting that PD98059, like FK506, affects the production of, rather than the responsiveness to growth-promoting cytokines. Accordingly, IL-2 production by T cells stimulated with anti-CD3 mAb in conjunction with PMA or with anti-CD28 mAb was inhibited by both compounds. However, these compounds differentially affected the production of other cytokines, depending on the mode of activation. PD98059 inhibited TNF-alpha, IL-3, granulocyte-macrophage (GM)-CSF, IFN-gamma, and to a lesser extent IL-6 and IL-10 production but enhanced IL-4, IL-5, and IL-13 production induced by CD3/PMA or CD3/CD28. FK506 suppressed CD3/PMA-induced production of all cytokines examined here but to a lesser extent IL-13. FK506 also reduced CD3/CD28-induced production of IL-3, IL-4, IL-10, TNF-alpha, and IL-6 but augmented that of GM-CSF, IL-5, IFN-gamma, and IL-13. Therefore, the biochemical targets of PD98059 and FK506 contribute differently to the production of various cytokines by T cells, which may have implications for the therapeutic manipulation of this production.


Similarities in glycosylation of human neuroblastoma tumors and cell lines.
The presence of fucosyl residues linked alpha 1----3(4) to N-acetylglucosamine was demonstrated on the oligosaccharides from glycoproteins of 11 human neuroblastoma tumors from ten different patients. This finding is in complete agreement with the previous report that human neuroblastoma cell lines contained an unusually large proportion of metabolically incorporated L-[3H]fucose in this specific linkage (U. V. Santer and M. C. Glick, Cancer Res., 43:4159-4166, 1983). Furthermore, the glycopeptides derived from the neuroblastoma tumors had a low percentage of fucose-containing biantennary oligosaccharides as determined by affinity to concanavalin A-Sepharose and in this characteristic were similar to glycopeptides from virus transformed and other tumor cells. To obtain these results, the tumor cells were labeled metabolically for 48 h with L-[3H]fucose. The cells were harvested and digested with Pronase, and the glycopeptides were isolated and treated with alpha-L-fucosidase from almonds, specific for the release of fucose linked alpha 1----3(4) to N-acetylglucosamine. A portion of the glycopeptides was characterized by serial affinity chromatography on immobilized concanavalin A and lentil lectin. The phenotypic similarity of the tumor cells to the cell lines, particularly CHP-134, included the paucity of biantennary oligosaccharides and the presence of fucosyl residues on the multiantennae of the glycopeptides.


Curcumin or bisdemethoxycurcumin for nose-to-brain treatment of Alzheimer disease? A bio/chemo-informatics case study.
The current study introduces a new idea of utilising several bio/chemoinformatics tools in comparing two bio-similar natural molecules viz. curcumin and bisdemethoxycurcumin (BDMC) in order to select a potential nose-to-brain remedy for Alzheimer disease. The comparison comprised several bio/chemo informatics tools. It encompassed all levels starting from loading the drug in a certain carrier; PLGA nanoparticles, to the biopharmaceutical level investigating the interaction with mucin and inhibition of P-gp blood-brain barrier efflux pumps. Finally, the therapeutic level was investigated by studying the interaction with pharmacological targets such as amyloid peptide plaques and cyclooxygenase2 enzyme responsible for the inflammatory reactions of the studied disease. The comparison revealed the superiority of curcumin over BDMC. Five new analogues were also hypothesised where diethoxybisdemethoxycurcumin was recommended as a superior molecule. This work introduced the virtual utilisation of bio/chemo informatics tools as a reliable and economic alternative to the exhausting and resources-consuming wet-lab experimentation.


The Mental Number Line in Dyscalculia: Impaired Number Sense or Access From Symbolic Numbers?
Numbers may be manipulated and represented mentally over a compressible number line oriented from left to right. According to numerous studies, one of the primary reasons for dyscalculia is related to improper understanding of the mental number line. Children with dyscalculia usually show difficulty when they have to place Arabic numbers on a physical number line. However, it remains unclear whether they have a deficit with the mental number line per se or a deficit with accessing it from nonsymbolic and/or symbolic numbers. Quebec French-speaking 8- to 9-year-old children with (24) and without (37) dyscalculia were assessed with transcoding tasks ( number-to-position and position-to-number) designed to assess the acuity of the mental number line with Arabic and spoken numbers as well as with analogic numerosities. Results showed that children with dyscalculia produced a larger percentage absolute error than children without mathematics difficulties in every task except the number-to-position transcoding task with analogic numerosities. Hence, these results suggested that children with dyscalculia do not have a general deficit of the mental number line but rather a deficit with accessing it from symbolic numbers.


Experimental investigation of dynamical coupling between turbulent transport and parallel flows in the JET plasma-boundary region.
The dynamical coupling between turbulent transport and parallel flows has been investigated in the plasma boundary region of the Joint European Torus tokamak. Experimental results show that there is a dynamical relationship between transport and parallel flows. As the size of transport events increases, parallel flows also increase. These results show that turbulent transport can drive parallel flows in the plasma boundary of fusion plasmas. This new type of measurement is an important element to unravel the overall picture connecting radial transport and flows in fusion plasmas.


Assessment of residual gastric volume and thirst in patients who drink before gastroscopy.
Before endoscopy patients undergo an uncomfortable fluid fast to reduce the risk of gastric acid aspiration and to ensure good endoscopic views are obtained. However, fluids rapidly leave the stomach and thus a long fluid fast before endoscopy may not be required. The object of this study was to establish whether drinking before endoscopy is safe and relieves patients' symptoms of thirst. 88 patients with American Society of Anaesthesiologists classification of physical status grades I and II were recruited in a controlled randomised single blind trial. The volume and pH of gastric aspirate obtained at gastroscopy was assessed in patients who drank 330 ml of water a minimum 90 minutes before their endoscopy and compared with values in patients who starved overnight. 44 patients who drank ('drinkers') 330 ml of water a mean 117 minutes before their morning gastroscopy had a similar volume and pH of gastric aspirate compared with 44 patients starved overnight ('starvers'); median volume 12.5 ml versus 10 ml, median pH 2.0 versus 2.0; 'drinkers' versus 'starvers' (NS). Before endoscopy patients were asked to score their thirst and hunger ratings as either none, mild, moderate or severe. Ratings for moderate and severe thirst were grouped together for analysis. The percentage of drinkers compared with starvers in each group with no thirst, mild thirst, and moderate severe thirst was 63%, 46%, and 37% respectively (chi 2 test for trend p < 0.05). Hunger ratings were similar in the two groups. It is safe for elective day cases to drink a significant volume of water two hours before endoscopy and this alleviates symptoms of thirst.


[Effect and Mechanism of Attapulgite and Its Modified Materials on Bioavailability of Cadmium in Soil].
The effect of attapulgite (magnesium aluminium phyllosilicate) and its modified materials on the extractability of soil Cd and the accumulation of Cd in lettuce (Lactuca sativa) were investigated using a pot-culture experiment, and the immobilization mechanism of attapulgite and its modified materials was explored through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The results showed that attapulgite and its modified materials could significantly reduce the Cd concentration in Lactuca sativa, with maximum reductions of 41.0% and 56.5%, respectively, and attapulgite modified materials treatments appeared more efficient than attapulgite treatments in reducing Cd uptake of Lactuca sativa. The saturated adsorption capacity for the adsorption of Cd2+ on attapulgite rose distinctly after being modified. Attapulgite and its modified materials could significantly reduce Cd content in soil CaCl2 extract at the dosage of 1%, with the maximum reduction rates of 34.2% and 34.3%, respectively. The attapulgite formed a complex to immobilize Cd mainly through the surface silanol and Cd2+ complexation reaction, while the modified attapulgite formed a complex mainly through the complexation of Cd2+ with carboxyl groups which existed in addition to the complexation with surface hydroxyl, thus reducing the mobility of Cd2+ and achieving remediation of Cd-contaminated soil. In summary, attapulgite and its modified materials can both be used for remediation of Cd-contaminated soil, and the mechanisms for this function were found to be different.


Effects of an electrostimulation training program on strength, jumping, and kicking capacities in soccer players.
The present study investigated the influence of a 5-week electrostimulation (EMS) training program on muscular strength, kicking velocity, sprint, and vertical jump performance in soccer players. Twenty amateur soccer players participated in the study, 10 in the electrostimulated group and the remaining 10 in a control group. Electrostimulation was applied on the quadriceps muscles over 5 weeks. Subjects were tested before, during (wk-3), and after (wk-5) the EMS training program. Maximal voluntary contraction using different contraction mode (i.e., eccentric, concentric, and isometric), vertical jump height, sprint running for 10 m, and ball speed were examined. We observed an increase in isometric and eccentric maximal knee extension torques and also a gain in ball speed performance without run up at wk-3. After 5 weeks of EMS training, eccentric, isometric, and concentric torques and ball speed had significantly improved. It appeared appropriate to conduct EMS training during at least 3 weeks to observe beneficial effects in specific soccer skills such as ball speed.


Risk of resistance to highly active antiretroviral therapy among HIV-positive injecting drug users: a meta-analysis.
Although highly active antiretroviral therapy (HAART) is an effective treatment for HIV, many physicians withhold this treatment from HIV-positive injecting drug users (IDUs) because of fears of non-adherence and consequent development of antiretroviral resistance. Little is known, however, about whether the rates of resistance differ between IDUs and non-IDUs. We did a meta-analysis of studies that compared antiretroviral resistance rates in IDUs (current or previous) with those in HIV-positive patients infected by other routes and who had never injected drugs. We used a random-effects model to investigate overall resistance rates and resistance to individual drug classes. Of 181 potential studies, 27 were eligible for review. We were able to extract data from 14 studies, but two were excluded because of a very small sample size of IDUs or data being available only from a secondary analysis. Thus we included 12 studies in the meta-analysis, involving 9055 patients, of which 2054 (23%) were IDUs. The risk of development of antiretroviral resistance did not differ significantly between IDU and non-IDU (odds ratio 1.04, 95% CI 0.74-1.45, p=0.84). Rates of loss to follow-up and virological failure were similar in IDU and non-IDU samples. Existing evidence does not support the common practice of withholding antiretroviral therapy from HIV-positive IDU on the basis of an elevated risk of antiretroviral resistance. Therapeutic guidelines should consider reassessment of this issue.


Regulation of equine herpesvirus type 1 gene expression: characterization of immediate early, early, and late transcription.
The regulation of equine herpesvirus type 1 (EHV-1) transcription was examined in infected rabbit kidney cells using metabolic inhibitors. In order to map EHV-1 immediate early, early, and late transcripts, viral RNA was 32P-labeled in vivo and hybridized to EHV-1 DNA restriction fragments immobilized on nitrocellulose filters. Immediate early viral RNA was mapped to one region of the viral genome within the inverted repeat DNA sequences (map units 0.78-0.83 and 0.95-1.0). Northern blot hybridization analysis using a 32P-labeled cloned DNA probe from this region identified a single immediate early viral transcript (approximately 6 kb). Transcription of early and late genes was not restricted to any specific region on the viral genome as indicated by the ability of 32P-labeled early and late RNA to hybridize to EHV-1 restriction endonuclease fragments from both the long and short components of EHV-1 DNA. Additional experiments performed without the use of metabolic inhibitors confirmed that EHV-1 transcription is temporally regulated. The characterization of EHV-1 transcription during productive infection will serve as a reference for the analysis of viral transcripts in oncogenically transformed and persistently infected cells.


Ultrasonographic screening in infants with isolated spinal strawberry nevi.
The authors performed spinal ultrasonography and/or magnetic resonance (MR) imaging in 20 consecutive newborns with spinal strawberry nevi. In 15 patients the strawberry nevi were isolated and in five they were associated with other cutaneous markers of occult spinal dysraphism (OSD). In four of five patients with additional cutaneous markers, but in none of those without, MR imaging and surgical exploration demonstrated OSD. The authors found that strawberry nevi in isolation do not appear to indicate underlying dysraphic states. The sparse clinical literature on this topic, which is reviewed, confirms an association between OSD and strawberry nevi presenting in conjunction with other cutaneous signatures. By contrast, spinal strawberry nevi occurring alone may not indicate the presence of underlying dysraphism. A prospective study of larger numbers of patients with isolated strawberry nevi, undergoing MR imaging evaluation, is necessary to determine whether neuroimaging screening in these patients is indicated.


Developing a unified list of physicians' reasoning tasks during clinical encounters.
The clinical reasoning literature focuses on how physicians reason while making decisions, rather than on what they reason about while performing their clinical tasks. In an attempt to provide a common language for discussing, teaching, and researching clinical reasoning, the authors undertook the task of developing a unified list of physicians' reasoning tasks, or what they reason about, during clinical encounters. The authors compiled an initial list of 20 reasoning tasks based on the literature from four content areas--clinical reasoning, communications, medical errors, and clinical guidelines. In the summer and fall of 2010, they surveyed a purposive sample of 46 international experts in clinical reasoning and communications. From the results of the first survey, the authors refined their list of reasoning tasks, then resurveyed 22 of the original participants. From the results of the second survey, they further refined their list and validated the inclusion of the reasoning tasks. Twenty-four of 46 (52%) and 15 of 22 (65%) participants completed the first- and second-round surveys, respectively. Following the second-round survey, the authors' list included 24 reasoning tasks, and a clinical example corresponding to each, that fell into four broad categories: framing the encounter (3), diagnosis (8), management (11), and self-reflection (2). The development of this unified list represents a first step in offering a vocabulary for discussing, reflecting on, teaching, and studying physicians' reasoning tasks during clinical encounters.


Serotype, antimicrobial susceptibility, and pathogenicity of Erysipelothrix rhusiopathiae isolates from tonsils of apparently healthy slaughter pigs.
Erysipelothrix rhusiopathiae was isolated from tonsils of 63 (10.5%) of 600 apparently healthy slaughter pigs in the Kanto area of Japan in February and July 1984. The isolation rate was significantly higher during July than in February. Of these 63 isolates, 34 isolates (54.0%) were serotype 7, 20 isolates (31.7%) were serotype 2, 6 isolates (9.5%) were serotype 6, and 1 isolate (1.6%) each was serotype 11, 12, or 16. All isolates of serotypes 2, 6, 11, 12, and 16 were highly virulent for mice, whereas most isolates of serotype 7 were weakly virulent. In swine, all isolates of serotype 2 were highly virulent, capable of inducing generalized urticarial lesions with depression and anorexia. On the other hand, 37 of 43 isolates of serotypes other than 2 induced no clinical signs, and the remaining 6 isolates induced local urticarial lesions at the site of inoculation in swine. The MIC of dihydrostreptomycin ranged from 1.56 to 100 micrograms/ml. All of the dihydrostreptomycin-resistant strains belonged to serotype 2. The high virulence of E. rhusiopathiae strains of serotype 2 harbored in the tonsils suggests a possible role of such strains in the cause of swine erysipelas. In contrast, members of the other nonvirulent or weakly virulent group, mainly serotype 7 strains, were considered to be resident in porcine tonsils.


Unequal access to treatment with intravenous alteplase for women with acute ischemic stroke.
A recent meta-analysis showed that women with acute ischemic stroke are less likely to receive treatment with intravenous alteplase than men. The aim of this study was to assess sex differences in treatment with intravenous alteplase and to explore the reasons for these differences. We analyzed data from the Promoting Acute Thrombolysis for Ischaemic Stroke (PRACTISE) study. We applied a multiple logistic regression model and expressed the association between sex and treatment with an age-adjusted odds ratio with 95% confidence interval. In total, 5515 patients were included in PRACTISE. Women were an average of 4 years older than men. The median National Institutes of Health Stroke Scale score was 6 in women and 5 in men. Fewer women were treated with intravenous alteplase (11% versus 14%; adjusted odds ratio, 0.8; 95% confidence interval, 0.7-1.0). However, fewer women arrived within 4 hours after onset (27% versus 33%; adjusted odds ratio, 0.8; 95% confidence interval, 0.7-0.9). Fewer women present themselves within 4 hours from stroke onset than men and consequently less often receive thrombolytic treatment. This difference may be caused by the older age of women on average and consequently women more often living alone. http://www.controlled-trials.com. Unique identifier: ISRCTN20405426.