The anomalous relaxivity of Mn3+ (TPPS4).
It was recently reported (C-W. Chen et al., FEBS Lett. 168, 70 (1984)) that water solutions of Mn3+ (TPPS4) have a surprisingly high relaxivity at 20 MHz and 37 degrees C, greater than most Mn2+ complexes including the hexaaquoion. Because Mn3+ (TPPS4) is highly stable, and porphyrins in general are tumor-seeking, we have sought to understand the origin of the large relaxivity by comparing the 1/T1 NMRD profiles (magnetic field dependence of 1/T1 of solvent protons) of Mn3+ (TPPS4) solutions with those of a number of other small Fe3+ and Mn2+ complexes. By relating the measured NMRD profiles to the theory of relaxation by magnetic dipolar interactions, in a form appropriate for small paramagnetic solute molecules, we establish that the theory affords an excellent quantitative description of the relaxation behavior of all the samples, and confirm that the relaxivity of Mn3+ (TPPS4) is anomalously high. The effect is attributed, in part, to the anisotropy of the ground-state wavefunction of Mn3+ in the porphyrin complex, effectively bringing the spin density of the Mn3+ ions closer to the protons of the coordinated water molecules than would a spherically symmetric S-state ion. In addition, the paramagnetic relaxation time of the Mn3+ spins, though short, is longer than would be anticipated for a non-S-state ion, and increases substantially with magnetic field above about 2 MHz. In this regard, Mn3+ (TPPS4) may be one of a class of molecules with properties particularly favorable for use as contrast-enhancing agents in magnetic resonance imaging.


Nitrogen translocation in a clonal dune perennial, Hydrocotyle bonariensis.
Hydrocotyle bonariensis, a common rhizomatous perennial of coastal North Carolina, forms extensive clones in dune systems characterized by a patchy nitrogen distribution. An experiment was conducted in which Hydrocotyle clones were grown across artificially created soil nitrogen gradients to determine: (1) the effect of soil nitrogen availability and nitrogen translocation on clonal structure and (2) the costs versus benefits of nitrogen translocation as measured by sexual and clonal reproduction. Acropetal translocation of nitrogen resulted in highly significant benefits to clones growing from areas of high N to areas of low N. Limited basipetal translocation was also demonstrated. Hydrocotyle ramets responded to increased nitrogen availability, from either intraclonal translocation or immediate uptake from the soil, by producing branches. Nitrogen level, however, had no effect on internode distances. Clonal integration of nitrogen, in tandem with a plastic morphology, allow Hydrocotyle clones to expand across a nitrogen-limited dune environment and to locally exploit nitrogen patches when they are encountered.


The Role of Sudanese Doctors in the United Kingdom in Mitigating COVID-19 Vaccine Hesitancy Among Their Diaspora Communities.
People from ethnic minority groups are at risk of adverse sequelae of COVID-19, but their vaccine acceptance and enrollment rates remain suboptimal. Diaspora communities are unique in that they continue to engage in epistemic networks related to vaccination with dwellers in their country of origin. We describe the COVID-19 vaccine awareness campaign we conducted from January 2021 to November 2021 for Sudanese diaspora groups in the United Kingdom and the various techniques and methods used by health care professionals from the same ethnocultural background to address vaccine reluctance among this cohort. We explore the impact of our joint efforts with local authorities in Sudan to overcome the initial barriers to the national vaccination program in Sudan. The influence of the intercommunication between the diaspora and their relatives at home regarding COVID-19 vaccine misinformation is also discussed. Finally, we highlight these observations as key areas for future research to improve the global impact of vaccine deployment in pandemic situations.


Simulated Patients in Physical Therapy Education: Systematic Review and Meta-Analysis.
Traditional models of physical therapy clinical education are experiencing unprecedented pressures. Simulation-based education with simulated (standardized) patients (SPs) is one alternative that has significant potential value, and implementation is increasing globally. However, no review evaluating the effects of SPs on professional (entry-level) physical therapy education is available. The purpose of this study was to synthesize and critically appraise the findings of empirical studies evaluating the contribution of SPs to entry-level physical therapy education, compared with no SP interaction or an alternative education strategy, on any outcome relevant to learning. A systematic search was conducted of Ovid MEDLINE, PubMed, AMED, ERIC, and CINAHL Plus databases and reference lists of included articles, relevant reviews, and gray literature up to May 2015. Articles reporting quantitative or qualitative data evaluating the contribution of SPs to entry-level physical therapy education were included. Two reviewers independently extracted study characteristics, intervention details, and quantitative and qualitative evaluation data from the 14 articles that met the eligibility criteria. Pooled random-effects meta-analysis indicated that replacing up to 25% of authentic patient-based physical therapist practice with SP-based education results in comparable competency (mean difference=1.55/100; 95% confidence interval=-1.08, 4.18; P=.25). Thematic analysis of qualitative data indicated that students value learning with SPs. Assumptions were made to enable pooling of data, and the search strategy was limited to English. Simulated patients appear to have an effect comparable to that of alternative educational strategies on development of physical therapy clinical practice competencies and serve a valuable role in entry-level physical therapy education. However, available research lacks the rigor required for confidence in findings. Given the potential advantages for students, high-quality studies that include an economic analysis should be conducted.


Effects of forest structure on the interaction between avian hosts, dipteran vectors and haemosporidian parasites.
Forest habitats are important biodiversity refuges for a wide variety of bird species. Parasitism may modulate host species presence and abundance, and parasite effects can change according to forest management practices. Such processes are not well studied in vector-borne avian haemosporidians. We analyzed the effects of forest management on bird-dipteran-haemosporidian interactions, using seven common bird species in managed and unmanaged beech forest habitats in northeastern Germany. We assumed that forest structural heterogeneity affects parasite population parameters in avian hosts (i.e., prevalence and parasitemia), through its effect on the condition of the avian host but also through varying vector abundances. Parasite prevalence was high (about 80%) and homogeneous across different beech forest categories (i.e., young, old, unmanaged) and for all bird species, except Erithacus rubecula (35%). Parasitemia varied across bird species but not across forest categories within each avian species (lowest parasitemia were found in E. rubecula, Turdus merula, and Turdus philomelos). In our study system, we found that vector abundance was not the main driver of parasite dynamics. We found that forest structure affects parasite infection probability directly and potentially host condition via available resources that have to be used either to combat infections (i.e., high parasitemia) or to maintain a good body condition. The effects of each of the predictors were bird species-specific, and we found that Diptera vectors were not the foremost influence in our host-vector-parasite system. Effects of forest habitat variables indicated that for most bird species in this study, habitat regulation of infection probability was more likely (i.e., E. rubecula, Fringilla coelebs, Sylvia atricapilla), whereas for Parus major habitat characteristics impacted first individuals' body condition and subsequently the probability of infection. Our findings emphasize the need of species-specific analyses and to use continuous forest structural parameters (e.g., the proportion of gap, south facing aspect) to better understand habitat and land use effects on host-vector-parasite dynamics.


Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway.
Quinolones (QNs)-induced arthropathy is an important toxic effect in immature animals leading to restriction of their therapeutic use in pediatrics. However, the exact mechanism still remains unclear. Recently, we have demonstrated that ofloxacin, a typical QN, induces apoptosis of alginate microencapsulated juvenile rabbit joint chondrocytes by disturbing the beta 1 integrin functions and inactivating the ERK/MAPK signaling pathway. In this study, we extend our initial observations to further elucidate the mechanism(s) of ofloxacin-induced apoptosis by utilizing specific caspase inhibitors. Pretreatment with both caspase-9-specific inhibitor zLEHD-fmk and caspase-8 inhibitor zIETD-fmk attenuated ofloxacin-induced apoptosis and activation of caspase-3 of chondrocyte in a concentration-dependent manner, as determined by fluorescent dye staining, enzyme activity assay and immunoblotting. Furthermore, the activation of caspase-9, -8 and -3 stimulated by ofloxacin was significantly inhibited in the presence of zIETD-fmk while pretreatment with zLEHD-fmk only blocked the activation of caspase-9 and -3. Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk. In addition, ofloxacin was found to increase the level of Bax, tBid, p53 in a concentration- and time-dependent manner. Taken together, The current results indicate that the caspase-8-dependent mitochondrial pathway is primarily involved in the ofloxacin-induced apoptosis of microencapsulated juvenile rabbit joint chondrocytes.


The relationship between panic attacks and chemical dependencies.
The purposes of the present study were to (a) determine the prevalence and characteristics of panic attacks in an alcohol/drug abuse inpatient population, (b) compare patients who reported experiencing panic attacks to patients who have never experienced a panic attack on various self-report measures of psychopathology and on ratings completed by Caregivers, and (c) to examine differences within groups of panickers. One hundred forty-four patients completed the questionnaires over a 17 week period. Over 50% of the patients reported experiencing one or more attacks in the three weeks prior to testing. These panickers scored higher than non-panickers on various measures of psychopathology. Over 83% of panickers reported using alcohol to self-medicate their panic attacks with almost 72% of them believing this procedure to be effective for preventing or reducing panic attacks. Male panickers differed from female panickers on several measures as did panickers who reported their panic attacks began before the alcohol abuse compared to those who did not believe this. The mean history of panic attacks was 103.4 months while the mean history of alcohol abuse was 134.6 months.


Nutrient regulation of pancreatic β-cell proliferation.
Excess consumption of energy-dense foods combined with a sedentary lifestyle is driving an obesity epidemic. Although obesity is closely associated with insulin resistance, most individuals meet the insulin demand by increasing their functional β-cell mass. Those who eventually develop type 2 diabetes are distinguished by a failure in this compensatory process. Although a causal role of insulin resistance in compensatory β-cell responses has received considerable experimental support, precisely how the β cell senses changes in the metabolic environment is still unknown. As metabolism of glucose, lipids and amino acids is profoundly altered in obesity, it is not surprising that these nutrients are conspicuous among the factors proposed to contribute. In this review we summarise our understanding of the role of nutrients, in particular glucose, fatty acids and amino acids in β-cell compensation with a particular emphasis on their relation to insulin resistance-induced factors and their underlying mechanism of action. Finally, we describe the concept of epigenetic programming and review recent studies illustrating how the status of the β cell epigenome is a product of its nutrient environment, and how metabolic programming of the β cell contributes to diabetes risk.


Daily and seasonal variations in the concentration of melatonin in the human pineal gland.
To elucidate whether pineal melatonin secretion is affected by changes in day length, we determined the concentration of melatonin in human pineal glands obtained at autopsy from 66 male subjects, aged 16-84 years over a period of 12 consecutive months. Based on the time of death, a day-night difference in pineal melatonin levels was evident only in the long photoperiod (April-September) with significantly higher melatonin concentrations occurring at night (2200-1000 h). Nighttime values in the long photoperiod were significantly higher than the nighttime values during the short photoperiod (October-March). During the short photoperiod, the data suggested a possible phase-delay in melatonin secretion. Day-night difference was evident in young subjects (30-60 years), but not in elderly subjects (61-84 years). Elderly subjects had lower total melatonin levels (day and night values) although statistically not significant. Therefore, melatonin levels did not decline with age and when the data were analyzed by age there was no significant day-night difference in melatonin levels. These data indicate that the concentration of melatonin in the human pineal is augmented only during the long photoperiod. The results suggest a partial effect of photoperiod on melatonin secretion in humans. This may result from living in an artificial light environment or due to other nonphotic signals involved in generating melatonin rhythm.


Local osmotic coupling to the active trans-endothelial bicarbonate flux in the rabbit cornea.
The present experiments investigate HCO3-, Cl- and fluid fluxes across partially destromalised corneas. Although there is no net flux of Cl-, there is a net flux of HCO-3 across the endothelium from stromal side to aqueous side which is accompanied by a flux of water in the same direction. Bulk phase osmosis cannot account for the initiation of the flux of fluid. Local osmotic coupling between ions and water is postulated to occur in the preparation. The exudate is hypertonic to the bathing Ringer solution.


Topical tazarotene: a review of its use in the treatment of plaque psoriasis.
Tazarotene (Tazorac) is a topical retinoid indicated for the treatment of plaque psoriasis. When used as monotherapy, topical tazarotene was effective at controlling signs and symptoms of plaque psoriasis, and had significantly lower post-treatment relapse rates than fluocinonide cream. The most common adverse events associated with tazarotene therapy are skin-associated events, such as pruritus, burning, and erythema. Combination therapy with tazarotene and mid-to-high potency topical corticosteroids generally resulted in a greater therapeutic effect than that with tazarotene alone, reduced the irritancy of tazarotene, and decreased the risk of post-treatment disease flare seen with corticosteroids; it also has the potential to reduce the degree of skin atrophy associated with topical corticosteroids. The combination of tazarotene and phototherapy also appears promising. Thus, tazarotene, as monotherapy or in combination with topical corticosteroids or UV light therapy, represents a useful treatment option in patients with plaque psoriasis.


[Bone metastases relapse after cementoplasty: Case report and discussion about the combination of radiotherapy and cementoplasty].
Interventional radiology techniques - vertebroplasty, kyphoplasty and vertebroplasty - are part of the therapeutic arsenal in oncology. They are not, however, antitumoural by themselves. A combination of these techniques with an antitumoral treatment is thus required. We present the case of a patient with a spinal metastasis who received antitumor vertebroplasty without additional treatment. The follow-up has found a tumour development around the cement. This case illustrates the need for a complementary antitumor treatment following a consolidative procedure. Many combinations of treatment and techniques have been published; however, no study reached a sufficient proof of efficiency for any combination to be recommended. Prospective trials are needed to guide clinicians.


Characterization of a novel full-length bovine endogenous retrovirus, BERV-β1.
Recent studies have suggested that certain classes of endogenous retroviruses (ERVs) may be present in cattle. The aim of this study was increase the scope of knowledge regarding bovine ERVs. The ovine ERV β1 pro/pol sequence was used to design a primer set for polymerase chain reaction (PCR) amplification of a similar sequence in the bovine genome. Through phylogenetic and bioinformatic analysis of the PCR product sequence together with its flanking region, a sequence 8107 bp in length was characterized. This sequence had a typical 5'-LTR-gag-pro-pol-env-LTR-3' organization, and phylogenetic investigation defined it as a bovine ERV β1. Thus, we were able to identify a novel bovine endogenous retrovirus element.


Association between serum anion gap and all-cause mortality in patients with acute myocardial infarction: A retrospective study based on MIMIC-IV database.
Although previous studies have reported that many biomarkers can determine the prognosis of patients with acute myocardial infarction (AMI), serum anion gap (AG) has not been well studied. We aimed to investigate the association between serum AG and mortality in patients with AMI. Adult patients first admitted to the ICU and diagnosed with AMI from 2008 to 2019 in the MIMIC-IV database were included. Patients were divided into the survival and non-survival groups based on 30-day and 90-day outcomes. According to the AG value (15.12 mmol/L) with a hazard ratio of 1 in the restricted cubic spline (RCS) analysis, patients were further divided into high and low AG groups. The Kaplan-Meier survival curve was plotted, and all-cause mortality was compared between the high and low groups using the log-rank test. Multivariate Cox regression analysis and RCS analysis were constructed to assess the relationship between AG and recent all-cause mortality in patients with AMI. 4446 patients were enrolled. The 30-day and 90-day mortality rates in the high AG group (25.53%, 31.75%) were higher than that in the low AG group (9.73%, 14.01%, P < 0.001) independently. The Kaplan-Meier curve showed that the 30-day and 90-day cumulative survival rates were lower in the high AG group than that in the low AG group (P < 0.001). RCS analysis showed that there was a non-linear relationship between AG and the risk of 90-day all-cause mortality in patients with AMI (χ2 = 18.680 P < 0.001). When AG was 15.12 mmol/L, its HR was about 1. Multivariable Cox regression analysis confirmed that increased AG was associated with higher 30-day and 90-day mortality. Elevated serum AG (≥15.12 mmol/L) is an independent predictor for short-term mortality in patients with AMI, and it may provide a basis for clinicians to identify patients with poor prognosis as early as possible.


Benefits of reducing prenatal exposure to coal-burning pollutants to children's neurodevelopment in China.
Coal burning provides 70% of the energy for China's industry and power, but releases large quantities of polycyclic aromatic hydrocarbons (PAHs) and other pollutants. PAHs are reproductive and developmental toxicants, mutagens, and carcinogens. We evaluated the benefit to neurobehavioral development from the closure of a coal-fired power plant that was the major local source of ambient PAHs. The research was conducted in Tongliang, Chongqing, China, where a coal-fired power plant operated seasonally before it was shut down in May 2004. Two identical prospective cohort studies enrolled nonsmoking women and their newborns in 2002 (before shutdown) and 2005 (after shutdown). Prenatal PAH exposure was measured by PAH-DNA adducts (benzo[a]pyrene-DNA) in umbilical cord blood. Child development was assessed by the Gesell Developmental Schedules at 2 years of age. Prenatal exposure to other neurotoxicants and potential confounders (including lead, mercury, and environmental tobacco smoke) was measured. We compared the cohorts regarding the association between PAH-DNA adduct levels and neurodevelopmental outcomes. Significant associations previously seen in 2002 between elevated adducts and decreased motor area developmental quotient (DQ) (p = 0.043) and average DQ (p = 0.047) were not observed in the 2005 cohort (p = 0.546 and p = 0.146). However, the direction of the relationship did not change. The findings indicate that neurobehavioral development in Tongliang children benefited by elimination of PAH exposure from the coal-burning plant, consistent with the significant reduction in PAH-DNA adducts in cord blood of children in the 2005 cohort. The results have implications for children's environmental health in China and elsewhere.


Biliary appendico-duodenostomy: a nonrefluxing conduit for biliary reconstruction.
Biliary conduits constructed during operations for choledochal cysts or biliary atresia are frequently complicated by reflux of gastrointestinal contents, stasis, and obstruction with resulting cholangitis. We have used the appendix as a biliary conduit for cases of biliary atresia and choledochal cyst, adapting the urologic technique of a tunneled, nonrefluxing anastomosis for reconstruction of the biliary tree--biliary appendico-duodenostomy (BAD). From our preliminary experience with this technique, it appears promising.


Design and synthesis of potent, orally active, inhibitors of carboxypeptidase U (TAFIa).
A series of 3-mercapto-propionic acid derivatives that function as reversible inhibitors of carboxypeptidase U have been prepared. We present a successful design strategy using cyclic, low basicity guanidine mimetics resulting in potent, selective and bioavailable inhibitors of carboxypeptidase U (TAFIa).


Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray.
Complete hydatidiform mole (CHM) is a type of gestational trophoblastic disease with pure paternal chromosome contribution and unpredictable malignant potential. As an attempt to assess the molecular pathogenesis of CHM, suppression subtractive hybridization (SSH) combined with cDNA microarray was used to compare the gene expression pattern of CHM compared with normal first-trimester placenta of similar gestational ages. cDNA microarray analysis using tissue-specific chips constructed with subtracted cDNA libraries identified 13 differentially expressed gene transcripts. Quantitative real-time polymerase chain reaction (PCR) confirmed up-regulation of human chorionic gonadotropin beta subunit (CGB) (P=0.0008) and KIAA1200 (P=0.0005), a G-protein regulator, as well as down-regulation of osteopontin (SPP1) (P<0.0001) in 14 genotyped CHM when compared with 15 normal placentas. These candidate genes may contribute toward understanding the mechanism involved with the development and progression of CHM.


Single-incision versus conventional laparoscopic pyloromyotomy for pediatric hypertrophic pyloric stenosis: a systematic review and meta-analysis.
To assess the safety and efficacy of single-incision versus conventional laparoscopic pyloromyotomy in pediatrics, we conducted a systematic review and meta-analysis. A literature search was conducted to identify studies that compared single-incision laparoscopic pyloromyotomy (SILP) and conventional laparoscopic pyloromyotomy (CLP) for infants with hypertrophic pyloric stenosis (HPS). Meta-analysis was used to pool and compare variables such as operative time, time to full feeding, length of hospital stay, mucosal perforation, inadequate pyloromyotomy, wound infection, incisional hernia and overall complications. Among the 490 infants with HPS in the seven studies, 205 received SILP and 285 received CLP. There was significant longer time to full feeding for SILP compared with CLP. However, pooling the results for SILP and CLP revealed no significant difference in operative time, length of hospital stay and postoperative complications. SILP is a safe, feasible and effective surgical procedure for infants with HPS when compared to CLP. SILP is equivalent to CLP in terms of operative time, length of hospital stay and postoperative complications. We conclude that LS should be considered an acceptable option for HPS.


Improved sensitivity of an acid sphingomyelinase activity assay using a C6:0 sphingomyelin substrate.
Short-chain C6-sphingomyelin is an artificial substrate that was used in an acid sphingomyelinase activity assay for a pilot screening study of patients with Niemann-Pick disease types A and B. Using previously published multiplex and single assay conditions, normal acid sphingomyelinase activity levels (i.e. false negative results) were observed in two sisters with Niemann-Pick B who were compound heterozygotes for two missense mutations, p.C92W and p.P184L, in the SMPD1 gene. Increasing the sodium taurocholate detergent concentration in the assay buffer lowered the activity levels of these two patients into the range observed with other patients with clear separation from normal controls.


A transient treatment of hippocampal neurons with alpha-tocopherol induces a long-lasting protection against oxidative damage via a genomic action.
Neuroprotection exerted by alpha-tocopherol against oxidative stress was investigated in cultured rat hippocampal neurons. In addition to its direct action as a radical scavenger revealed at concentrations above 10 microM, a transient application of 1 microM alpha-tocopherol phosphate (alpha-TP) to neurons induced a complete delayed long-lasting protection against oxidative insult elicited by exposure to Fe2+ ions, but not against excitotoxicity. A minimal 16-h application of alpha-TP was required to observe the protection against subsequent oxidative stress. This delayed protection could last up to a week after the application of alpha-TP, even when medium was changed after the alpha-TP treatment. Cycloheximide, added either 2 h before or together with alpha-TP, prevented the delayed neuroprotection, but not the acute. However, cycloheximide applied after the 16-h alpha-TP pretreatment did not alter the delayed neuroprotection. Neither Trolox, a cell-permeant analogue of alpha-tocopherol, nor other antioxidants, such as epigallocatechin-gallate and N-acetyl-L-cysteine, elicited a similar long-lasting protection. Only tert-butylhydroquinone could mimic the alpha-TP effect. Depletion of glutathione (GSH) by L-buthionine sulfoximine did not affect the delayed alpha-TP protection. Thus, in addition to its acute anti-radical action, alpha-TP induces a long-lasting protection of neurons against oxidative damage, via a genomic action on antioxidant defenses apparently unrelated to GSH biosynthesis.


Assessment of quality of movement during a lateral step-down test: Narrative review.
Altered lower limb movement patterns during weight-bearing activities have been described as risk factors for several injuries. The lateral step-down test (LSD) was developed to be a simple, clinician-friendly tool to facilitate the assessment of lower extremity quality of movement during a functional activity. However, there is still conflicting information across the literature regarding how the LSD should be performed. To critically review the literature regarding the assessment of quality of movement using the LSD and to provide an overview of how this test has been used, describing confounding factors and factors associated with altered movement patterns. A literature review was conducted in PubMed/MEDLINE, COCHRANE, PEDro, SciELO and LILACS databases, by two independent reviewers. Sixteen articles met the inclusion criteria. One was a prospective cohort study to identify risk factors for injuries in military recruits. The fifteen remaining were cross-sectional studies involving healthy military recruits, physically active individuals, athletes and/or sedentary subjects, as well as participants with knee and ankle disorders. Worst quality of movement during the LSD has been associated with deficits in hip external rotation and knee extension strength as well as in ankle dorsiflexion range of motion. The reliability of the LSD has been reported to be moderate (κ = 0.59-0.81). The LSD has adequate reliability and is a simple tool that can be used to quantify lower extremity quality of movement. Future studies should include standardized methods for application, scoring and interpretation of the test, so that confounding factors can be minimized.


Is the response to recombinant alpha interferon related to the presence of antibodies to hepatitis C virus in patients with chronic non-A, non-B hepatitis?
The purpose of this study was to determine whether the response of serum alanine aminotransferase (ALT) to recombinant alpha-interferon was related to the presence or absence of antibodies to hepatitis C virus (anti-HCV) in patients with chronic non-A,non-B hepatitis. A group of 65 patients with chronic non-A, non-B hepatitis was studied. The source of contamination was blood transfusion or administration of blood products in 32, intravenous drug addiction in 14 and unknown in 19. The patients received 1, 3 or 5 MU of recombinant alpha-interferon, three times a week, for 6 months. A complete response was defined as normal ALT by the end of recombinant alpha-interferon treatment. Sera collected before treatment were tested for anti-HCV with an enzyme immunoassay. The overall percentage of anti-HCV positive patients in the study group was 75%. There was no difference between the anti-HCV positive and the anti-HCV negative patients before the treatment with respect to age, sex ratio, source of contamination, serum albumin, prothrombin, bilirubin, ALT or prevalence of cirrhosis. In the anti-HCV positive and the anti-HCV negative groups, there was no difference in the proportion of patients receiving the 1, 3 or 5 MU dosage. The percentage of patients with complete response was not different in anti-HCV positive patients (48%) and in anti-HCV negative patients (50%). There was also no difference in the kinetics of the decrease of mean serum ALT levels between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment of depression in patients with heart disease.
There is a growing body of evidence that depression significantly and adversely affects cardiovascular health. Perhaps the most prominent finding is the documented increase in mortality rate in patients with depression after myocardial infarction. The critical questions of interest to both the clinician and researcher are whether there are safe and effective treatments for depression in patients with heart disease and whether treatment of depression reduces the increased risk of cardiac morbidity and mortality. Though the data are limited and are primarily from open or comparator trials, the tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and specific psychotherapies appear to be effective for treatment of depression in patients with ischemic heart disease (IHD), and response rates are comparable to those reported in depressed patients without heart disease; however, there has been only one placebo-controlled trial to date, and therefore it is premature to come to definitive conclusions regarding the efficacy of antidepressant therapies in this patient population. With respect to safety, the TCAs are associated with documented adverse cardiovascular effects, including increases in heart rate, orthostatic hypotension, and conduction delays. Use of TCAs in patients with IHD carries a proven increased risk of cardiac morbidity and perhaps of mortality as well. The SSRIs appear to be relatively safe and effective treatment for depression in patients with comorbid IHD.


Elevation of arterial phosphorfuctokinase activity associated with susceptibility to atherosclerosis in pigeons.
The activity of phosphofructokinase (PFK, 126.96.36.199) was measured in arteries of very young (5-8 week old) pigeons known to differ in susceptibility to atherosclerosis. The activity of the arterial enzyme was significantly higher in the atherosclerosis-susceptible White Carneau (WC) pigeons than in the resistant Show Racers (SR). The difference was significant whether enzyme activity was calculated on the basis of extract protein, DNA content or fat-free dry weight. In the White Carneau arteries the activity of the enzyme was higher in the female than the male pigeons. PFK is a key regulatory enzyme of glycolysis and is subject to fine control adjustments. A low ATP/ADP ratio and a fall in citrate concentration, as for example, induced by hypoxia, are meditors of a feedback mechanism leading to a rise in PFK activity and enhancement of glycolysis for energy production. This mechanism appears to be the cause of the higher PFK activity in the WC arteries, because related studies indicate impaired Krebs cycle activity in these vessels. It is suggested that the increased dependence of the WC arteries on glycolysis facilitates the development of atherosclerosis in this pigeon strain and that the mechanism is similar to the mechanism by which tissue hypoxia causes lipid accumulation and connective tissue alterations in the arterial wall.


Vessel Wall MR Imaging in the Pediatric Head and Neck.
Vessel wall MR imaging (VWI) is a technique that progressively has gained traction in clinical diagnostic applications for evaluation of intracranial and extracranial vasculopathies, with increasing use in pediatric populations. The technique has shown promise in detection, differentiation, and characterization of both inflammatory and noninflammatory vasculopathies. In this article, optimal techniques for intracranial and extracranial VWI as well as applications and value for pediatric vascular disease evaluation are discussed.


Release of 5-ASA from Pentasa in patients with Crohn's disease of the small intestine.
Pentasa is a controlled-release tablet made from semipermeable microspheres and designed to continuously deliver therapeutic quantities of 5-ASA (5-aminosalicylic acid) throughout the gastrointestinal tract. Scintigraphic studies in healthy subjects have documented that 5-ASA release could occur in the small intestine. We tested here the disintegration of Pentasa in the digestive tract of nine patients with Crohn's disease of the small intestine. Each patient was given, after breakfast, a 250 mg tablet of Pentasa containing samarium-153 oxide. For 8 h the progression of the isotope in the gastrointestinal tract was followed using gamma camera scintigraphy. Plasma measurement of 5-ASA and acetylated 5-ASA was used to verify the liberation and absorption of 5-ASA. The Pentasa tablet appeared completely dissolved in the stomach by 117 +/- 18 min. Samarium oxide was first detected in the small intestine 60 +/- 5 min after its ingestion; it reached the colon after 280 +/- 13 min and it was completely absent from the small intestine at 360 +/- 26 min. Plasma concentrations of 5-ASA started to rise after 67 +/- 7 min and were maximal at 222 +/- 25 min. In patients with Crohn's disease of the small intestine, Pentasa microgranules start releasing 5-ASA in the proximal small intestine, acting locally to exert its beneficial effect.


Unusual aetiology of isolated lower motor neuron facial palsy: systemic lupus erythematosus presenting with cranial nerve palsy and nephritis.
A 20-year-old woman presented with common cold symptoms was found to have a left-sided facial droop. On examination, peripheral facial nerve palsy was confirmed. Subsequent testing showed nephrotic range proteinuria and positive serologies including antinuclear antibody and anti-smith antibody. Kidney biopsy showed stage III lupus nephritis. Treatment with pulse steroids along with mycophenolate mofetil for her lupus nephritis resulted in concomitant improvement of her facial palsy.


Carcinogenicity of 8-nitroquinoline in Sprague-Dawley rats.
8-Nitroquinoline was added to the semisynthetic diet of outbred Sprague-Dawley rats for 48 weeks. Squamous cell carcinomas of the upper digestive tract (tongue and esophagus), but especially of the forestomach, occurred among the higher concentration groups. Squamous cell carcinoma of the forestomach occurred in 3 of 11 (27.3%) rats in the 2500 ppm group and 7 of 35 (20.0%) rats in the 1000 ppm group. Three cases of lung adenoma were also observed in the 2500 ppm group. Results clearly indicate that 8-nitroquinoline is carcinogenic in rats when administered orally in a semisynthetic diet.


Dynamics of blood flow: modeling of Fåhraeus and Fåhraeus-Lindqvist effects using a shear-induced red blood cell migration model.
Blood flow in micro capillaries of diameter approximately 15-500 μm is accompanied with a lower tube hematocrit level and lower apparent viscosity as the diameter decreases. These effects are termed the Fåhraeus and Fåhraeus-Lindqvist effects, respectively. Both effects are linked to axial accumulation of red blood cells. In the present investigation, we extend previous works using a shear-induced model for the migration of red blood cells and adopt a model for blood viscosity that accounts for the suspending medium viscosity and local hematocrit level. For fully developed hematocrit profiles (i.e., independent of axial location), the diffusion fluxes due to particle collision frequency and viscosity gradients are of equal magnitude and opposite directions. The ratio of the diffusion coefficients for the two fluxes affects both the Fåhraeus and Fåhraeus-Lindqvist effects and is found related to the capillary diameter and discharge hematocrit using a well-known data-fit correlation for apparent blood viscosity. The velocity and hematocrit profiles were determined numerically as functions of radial coordinate, tube diameter, and discharge hematocrit. The velocity profile determined numerically is consistent with the derived analytical expression and the results are in good agreement with published numerical results and experimental data for hematocrit ratio and hematocrit and velocity profiles.


Advanced glycation end-products and its soluble receptor are not independent predictors of incident dysglycaemia or metabolic syndrome in women with polycystic ovary syndrome: a prospective observational study.
To evaluate the association of serum advanced glycation end-products (AGEs) and its soluble receptor of AGE (sRAGE) levels with dysglycaemia and metabolic syndrome in women with polycystic ovary syndrome (PCOS). This was an analysis of a cohort of women with PCOS who were prospectively recruited for a longitudinal observational study on their endocrine and metabolic profile between January 2010 and December 2013. The association of serum AGEs and sRAGE levels with dysglycaemia and metabolic syndrome at the second-year visit (the index visit) and the sixth-year visit (the outcome visit) were determined. Comparisons of continuous variables between groups were made using the Mann-Whitney U-test. Spearman test was used for correlation analysis. Multivariate binary logistic regression analysis was employed to identify the factors independently associated with the outcome events. A total of 329 women were analysed at the index visit. Significantly lower serum levels of sRAGE (both p < 0.001), but no significant difference in AGEs, were observed in those with dysglycaemia or metabolic syndrome. At the outcome visit, those with incident metabolic syndrome had a significantly lower initial serum sRAGE levels (p = 0.008). The association of serum sRAGE with dysglycaemia and metabolic syndrome at the index visit was no longer significant in multivariate logistic regression after controlling for body mass index, free androgen index and homeostatic model assessment for insulin resistance (HOMA-IR). sRAGE was also not significantly associated with incident metabolic syndrome at the outcome visit on multivariate logistic regression. Serum sRAGE levels are significantly lower in women with PCOS who have dysglycaemia or metabolic syndrome, and in those developing incident metabolic syndrome in four years. However, it does not have a significant independent association with these outcome measures after adjusting for body mass index, free androgen index and HOMA-IR.


UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis.
Ovarian cancer is one of the important factors that seriously threaten women's health and its morbidity and mortality ranks eighth among female cancers in the world. It is critical to identify potential and promising biomarkers for prognostic evaluation and molecular therapy of OV. Ubiquitin-conjugating enzyme E2S (UBE2S), a potential oncogene, regulates the malignant progression of various tumors; however, its role in OV is still unclear. The expression and prognostic significance of UBE2S at the pan-cancer level were investigated through high-throughput gene expression analysis and clinical prognostic data from TCGA, GEPIA, and GEO databases. 181 patients with OV were included in this study. Cell culture and cell transfection were performed on OV cell lines (SKOV3 and A2780) and a normal ovarian cell line (IOSE80). The expression level and prognostic significance of UBE2S in OV were verified by western blot, immunohistochemistry, and Kaplan-Meier survival analysis. Through cell transfection, CCK-8, Ki-67 immunofluorescence, wound healing, Transwell, clonogenic, and flow cytometry assays, the effect and detailed mechanism of UBE2S knockdown on the malignant biological behavior of OV cells were explored. UBE2S exhibited abnormally high expression at the pan-cancer level. The results of RT-qPCR and Western blotting indicated that UBE2S was significantly overexpressed in ovarian cancer cell lines compared with normal cell lines (P < 0.05). Kaplan-Meier survival analysis and Immunohistochemistry indicated that overexpression of UBE2S was related to poor prognosis of OV (HR > 1, P < 0.05). Results of in vitro experiments indicated that UBE2S gene knockdown might inhibit the proliferation, invasion, and prognosis of OV cells by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby blocking the cell cycle and promoting apoptosis (P < 0.05). UBE2S is a potential oncogene strongly associated with a poor prognosis of OV patients. Knockdown of UBE2S could block the cell cycle and promote apoptosis by inhibiting the PI3K/AKT/mTOR pathway and ultimately inhibit the proliferation, migration and prognosis of ovarian cancer, which suggested that UBE2S might be used for molecular therapy and prognostic evaluation of ovarian cancer.


2-(1H-Pyrazol-4-yl)acetic acids as CRTh2 antagonists.
High throughput screening identified the pyrazole-4-acetic acid substructure as CRTh2 receptor antagonists. Optimisation of the compounds uncovered a tight SAR but also identified some low nanomolar inhibitors.


Dysphagia Following Putaminal Hemorrhage at a Rehabilitation Hospital.
Dysphagia occurs frequently during the acute phase of cerebral hemorrhage; however, there are few reports of dysphagia associated with cerebral hemorrhage in the subacute and chronic phase. We focused on putaminal hemorrhage at a rehabilitation hospital and evaluated the relationships between the frequencies of dysphagia, focus, and hematoma volume and type. A hundred patients with putaminal hemorrhage referred to our rehabilitation hospital were evaluated. Bedside swallowing assessments (BSAs) were conducted and results were evaluated relative to the information obtained on computed tomography imaging, including hematoma type and volume, and oral intake at the time of admission/discharge from the hospital. A regular diet was provided to 48 patients, dysphagia diet to 44 patients, and enteral feeding to 8 patients. There were significant feeding group differences in age, hematoma volume and type, existence of ventricle rupture, neurological manifestation, cognitive function, existence of unilateral neglect and aphasia, initial BSA, activities of daily living (ADL) score using the Functional Independence Measure at the time of admission/discharge from the hospital, and length of stay. At discharge, we provided a regular diet to 81 patients and dysphagia diet to 19 patients. Age and ADL score had the greatest influence on oral intake at the time of discharge from the hospital. The prognosis of dysphagia caused by putaminal hemorrhage is good, with no patient requiring enteral feeding, although putaminal hemorrhage often causes dysphagia. Patient age and ADL score on admission are used to predict the residual factors of dysphagia.


The disc and the field in glaucoma.
The previous descriptions of the optic nerve head were reviewed. A study was done using discriminant analysis, in which an 85% separation was obtained by means of the discriminant function in a prospective study. The false positives showed a higher incidence of subsequent visual field defects from the true negatives. The pitfalls of the use of the optic nerve head appearance in the recognition of glaucomatous visual field defects were discussed.


Bisphenol A and chronic disease risk factors in US children.
To evaluate the relationship between urinary bisphenol A (BPA) levels and measures of adiposity and chronic disease risk factors for a nationally representative US pediatric sample. We used the NHANES 2003-2010 to evaluate cross-sectional associations between urinary BPA and multiple measures of adiposity, cholesterol, insulin, and glucose for children aged 6 to 18 years, adjusting for relevant covariates (eg, demographics, urine creatinine, tobacco exposure, and soda consumption). We found a higher odds of obesity (BMI ≥95th percentile) with increasing quartiles of BPA for quartiles 2 vs 1 (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.17-2.60, P = .008), 3 vs 1 (OR 1.64, 95% CI 1.09-2.47, P = .02), and 4 vs 1 (OR 2.01, 95% CI 1.36-2.98, P = .001). We also found a higher odds of having an abnormal waist circumference-to-height ratio (quartiles 2 vs 1 [OR 1.37, 95% CI 0.98-1.93, P = .07], 3 vs 1 [OR 1.41, 95% CI 1.07-1.87, P = .02], and 4 vs 1 [OR 1.55, 95% CI 1.12-2.15, P = .01]). We did not find significant associations of BPA with any other chronic disease risk factors. Higher levels of urinary BPA were associated with a higher odds of obesity (BMI >95%) and abnormal waist circumference-to-height ratio. Longitudinal analyses are needed to elucidate temporal relationships between BPA exposure and the development of obesity and chronic disease risk factors in children.


Structure of myxovirus resistance protein a reveals intra- and intermolecular domain interactions required for the antiviral function.
Human myxovirus resistance protein 1 (MxA) is an interferon-induced dynamin-like GTPase that acts as a cell-autonomous host restriction factor against many viral pathogens including influenza viruses. To study the molecular principles of its antiviral activity, we determined the crystal structure of nucleotide-free MxA, which showed an extended three-domain architecture. The central bundle signaling element (BSE) connected the amino-terminal GTPase domain with the stalk via two hinge regions. MxA oligomerized in the crystal via the stalk and the BSE, which in turn interacted with the stalk of the neighboring monomer. We demonstrated that the intra- and intermolecular domain interplay between the BSE and stalk was essential for oligomerization and the antiviral function of MxA. Based on these results, we propose a structural model for the mechano-chemical coupling in ring-like MxA oligomers as the principle mechanism for this unique antiviral effector protein.


APT-Net: Adaptive encoding and parallel decoding transformer for medical image segmentation.
There are limitations in the study of transformer-based medical image segmentation networks for token position encoding and decoding of images. The position encoding module cannot encode the position information adequately, and the serial decoder cannot utilize the contextual information efficiently. In this paper, we propose a new CNN-transformer hybrid structure for the medical image segmentation network APT-Net based on the encoder-decoder architecture. The network introduces an adaptive position encoding module for the fusion of position information of a multi-receptive field to provide more adequate position information for the token sequences in the transformer. In addition, the dual-path parallel decoder's basic and guide information paths simultaneously process multiscale feature maps to efficiently utilize contextual information. We conducted extensive experiments and reported a number of important metrics from multiple perspectives on seven datasets containing skin lesions, polyps, and glands. The IoU reached 0.783 and 0.851 on the ISIC2017 and Glas datasets, respectively. To the best of our knowledge, APT-Net achieves state-of-the-art performance on the Glas dataset and polyp segmentation tasks. Ablation experiments validate the effectiveness of the proposed adaptive position encoding module and the dual-path parallel decoder. Comparative experiments with state-of-the-art methods demonstrate the high accuracy and portability of APT-Net.


Posterior-inferior glenoid rim shapes by MR imaging.
Our purpose was to try to apply a CT classification of glenoid rim shapes to MR images and to determine the reliability of the subsequent MR classification by testing observer variability. Shoulder MR imaging exams of 54 consecutive patients were reviewed retrospectively by two musculoskeletal radiologists independently. Posterior-inferior glenoid rim shape was categorized, based on reported CT criteria, as triangle, "lazy-J" or "delta" using the most caudal MR section that unequivocally showed articular cartilage. The same studies were reviewed again one month later to test interobserver and intraobserver variability. Final determination of glenoid rim type was made by consensus. There were 31 males and 23 females with an average age of 42 years, range 14-75 years. Forty-one patients were referred for evaluation of nonspecific shoulder pain, 9 for suspected rotator cuff tear and 4 for instability. The most common shape was "lazy-J" with 32 patients (59%) having this type. The least common was delta shape, with 7 patients (13%) having this form. Fifteen patients (28%) had a normal triangle shape. There was significant interobserver variability in determining the shape of the glenoid rim with 17/54 (31%) discordant readings. For the "lazy-J" shape, the kappa value was .02, for the "delta" type, kappa value was .60 and for the triangle shape, kappa was .32. Intraobserver variability was 35% for radiologist A and 28% for radiologist B. Kappa values for intraobserver variability ranged from .53 to .85. Four patients had posterior instability, 3 were judged to have normal triangular inferior glenoid rims and 1 a "lazy J" type by Radiologist A. Radiologist B judged 2 of the instability patients as normal triangular and 2 as "lazy J". A CT classification of posterior-inferior glenoid rim shapes can be applied using MR imaging, however, there is significant observer variability that limits the applicability of this classification scheme with MR imaging.


Perfluorocarbons for the treatment of decompression illness: how to bridge the gap between theory and practice.
Decompression illness (DCI) is a complex clinical syndrome caused by supersaturation of respiratory gases in blood and tissues after abrupt reduction in ambient pressure. The resulting formation of gas bubbles combined with pulmonary barotrauma leads to venous and arterial gas embolism. Severity of DCI depends on the degree of direct tissue damage caused by growing bubbles or indirect cell injury by impaired oxygen transport, coagulopathy, endothelial dysfunction, and subsequent inflammatory processes. The standard therapy of DCI requires expensive and not ubiquitously accessible hyperbaric chambers, so there is an ongoing search for alternatives. In theory, perfluorocarbons (PFC) are ideal non-recompressive therapeutics, characterized by high solubility of gases. A dual mechanism allows capturing of excess nitrogen and delivery of additional oxygen. Since the 1980s, numerous animal studies have proven significant benefits concerning survival and reduction in DCI symptoms by intravenous application of emulsion-based PFC preparations. However, limited shelf-life, extended organ retention and severe side effects have prevented approval for human usage by regulatory authorities. These negative characteristics are mainly due to emulsifiers, which provide compatibility of PFC to the aqueous medium blood. The encapsulation of PFC with amphiphilic biopolymers, such as albumin, offers a new option to achieve the required biocompatibility avoiding toxic emulsifiers. Recent studies with PFC nanocapsules, which can also be used as artificial oxygen carriers, show promising results. This review summarizes the current state of research concerning DCI pathology and the therapeutic use of PFC including the new generation of non-emulsified formulations based on nanocapsules.


PEG allergy - A COVID-19 pandemic-made problem? A German perspective.
Polyethylene glycol (PEG) has been used for decades, but only caused allergic reactions exceptionally. Introduction of PEG-containing COVID-19 vaccines might have fostered public interest beyond medical reasoning. To investigate the impact of the SARS-CoV-2 pandemic on the public interest in PEG allergy in Germany and the published PEG allergy cases worldwide. A retrospective longitudinal study was conducted to measure public interest in PEG allergy analyzing Google search volume in Germany from February 2018 to January 2022. Medically confirmed "PEG allergy" cases were analyzed by looking at the numbers of PubMed case reports and case series from 1977 until January 2022. Web results in Germany before COVID-19 show search volumes related to "PEG allergy/testing" was negligible, with 10 search queries per month. The pandemic led to a >200-fold increase from 250 queries 2 years before to 55 720 queries 2 years thereafter, reflecting tremendous public interest. Additionally, the maximum monthly search volume from before to during the pandemic increased immensely for "vaccination" (57-fold), "vaccination and adverse effects" (85-fold), "vaccination and allergy" (71-fold). In contrast, the increase of publication numbers for the search term "PEG allergy" was small from 2019 to 2021 (2.5-fold). Only a very low number of 211 cases with "PEG allergy" worldwide since 1977 could be identified. PEG allergy became a topic of major public interest because of COVID-19 vaccination. Scientific publications have increased to a lesser extent, probably promoted by public awareness. Conversely, the overall number of cases published with PEG allergy remain very low. The current high demand for COVID-19 vaccination allergy testing is triggered by public interest instead of medical reasoning.


α-Azido Esters in Depsipeptide Synthesis: C-O Bond Cleavage during Azido Group Reduction.
α-Azido esters, when treated with dithiothreitol (DTT)/diisopropylethylamine (DIPEA), undergo both azido group reduction to give α-amino esters and C-O bond cleavage to give triazoles. The extent of triazole formation depends upon leaving group ability. Some C-O bond cleavage via triazole formation was also found to occur when a resin-bound peptide, which contained a terminal α-azido ester group, was treated with DTT/DIPEA. C-O bond cleavage also took place when this peptide was treated with PPh3, PBu3, or PMe3; however, in these cases, C-O bond cleavage occurred via either triazole formation and/or hydrolysis of the ester bond in the iminophosphorane intermediate to give betaines. The mechanism that dominated for C-O bond cleavage depended upon the phosphine that was used for azido group reduction. C-O bond cleavage during reduction of the azido group in the peptide was minimized by performing the reduction with PBu3 in the presence of a symmetric anhydride derived from an amino acid in dry THF followed by the addition of water. Surprisingly, these conditions provided the amine as the major product, while the expected amide was formed as a minor product. These conditions were employed in an improved synthesis of an analogue of the cyclic lipodepsipeptide antibiotic daptomycin.


Generic estimator of biomass concentration for Escherichia coli and Saccharomyces cerevisiae fed-batch cultures based on cumulative oxygen consumption rate.
The focus of this study is online estimation of biomass concentration in fed-batch cultures. It describes a bioengineering software solution, which is explored for Escherichia coli and Saccharomyces cerevisiae fed-batch cultures. The experimental investigation of both cultures presents experimental validation results since the start of the bioprocess, i.e. since the injection of inoculant solution into bioreactor. In total, four strains were analyzed, and 21 experiments were performed under varying bioprocess conditions, out of which 7 experiments were carried out with dosed substrate feeding. Development of the microorganisms' culture invariant generic estimator of biomass concentration was the main goal of this research. The results show that stoichiometric parameters provide acceptable knowledge on the state of biomass concentrations during the whole cultivation process, including the exponential growth phase of both E. coli and S. cerevisiae cultures. The cell culture stoichiometric parameters are estimated by a procedure based on the Luedeking/Piret-model and maximization of entropy. The main input signal of the approach is cumulative oxygen uptake rate at fed-batch cultivation processes. The developed noninvasive biomass estimation procedure was intentionally made to not depend on the selection of corresponding bioprocess/bioreactor parameters. The precision errors, since the bioprocess start, when inoculant was injected to a bioreactor, confirmed that the approach is relevant for online biomass state estimation. This included the lag and exponential growth phases for both E. coli and S. cerevisiae. The suggested estimation procedure is identical for both cultures. This approach improves the precision achieved by other authors without compromising the simplicity of the implementation. Moreover, the suggested approach is a candidate method to be the microorganisms' culture invariant approach. It does not depend on any numeric initial optimization conditions, it does not require any of bioreactor parameters. No numeric stability issues of convergence occurred during multiple performance tests. All this makes this approach a potential candidate for industrial tasks with adaptive feeding control or automatic inoculations when substrate feeding profile and bioreactor parameters are not provided.


p53, Bax and Bcl-2 in vivo expression in the murine thymus after apoptogenic treatments.
Neoplasia can results from a lack of cell elimination by apoptosis. In order to determine if mechanisms controlling apoptosis are disturbed during neoplastic transformation in a model of murine radio-induced thymic lymphomas, we have assessed the kinetics of p53, Bax and Bcl-2 in situ expression after induction of thymic apoptosis by irradiation or glucocorticoids at first in normal mice. TUNEL method was used for in situ detection of apoptosis and protein expression was determined by indirect immunohistochemistry. After hydrocortisone injection, levels of p53 and Bax, but not Bcl-2, expression were raised. A whole body sublethal irradiation led to an increase of p53 and Bcl-2, but not Bax, expression. This is the first in vivo report of in situ protein expression in the thymus after apoptogenic treatments of mice. The results suggest that Bax could be involved in glucocorticoid-mediated apoptosis. The increased levels of Bcl-2 expression are discussed.


Reappraisal of a 20-year experience with the radial artery as a conduit for coronary bypass grafting.
This study aimed at evaluating the clinical and angiographic results of the radial artery (RA) used as a coronary bypass graft over 20 years. Clinical follow-up was obtained in 563 patients at 9.2 years. Angiographic follow-up was obtained in 351 patients with opacification of 1427 conduits, including 629 RA at 7.0 years. At 9.2 years, freedom from overall and cardiovascular death was 80.3% and 92.7%, respectively. Symptoms were: acute myocardial infarction: 2.1% (n=12); angina: 17.4% (n=98), and congestive heart failure 10.6% (n=60). Percutaneous revascularization was required in 13.5% (n=76) of cases on: native coronary (n=77), RA conduit (n=21), and other graft (n=7). Reoperation was needed in 2.3% (n=13) of cases for valve replacement (n=10) and redo coronary artery bypass grafting (CABG) (n=3). At 7.0 years, RA patency was 82.8% (521/629) and was lower than that of left internal mammary artery (IMA), 95.5% (491/514) (p<0.001); similar to right IMA, 87.9% (51/58, p=0.32); free IMA, 80.0% (44/55, p=0.60); and vein, 81.9% (140/171, p=0.77). RA patency was lower in the case of myocardial ischemia: 74.0% (174/235) versus 88.1% (347/394) in asymptomatics (p<0.001). RA patency was higher for diagonal (93.1% (95/102)) compared to circumflex (82.5% (274/332, p<0.01)) and right coronary (77.6% (146/188, p<0.001)). Calcium channel blockers had no impact on RA patency. Separating four groups at successive follow-up intervals, RA patency was: 86.2%, 81.9%, 81.4%, and 81.6% at 1.0, 5.4, 8.3, and 13.1 years, respectively. CABG with the RA offered long-lasting clinical benefit. Beyond the first postoperative year during which some attrition was observed, RA patency was remarkably stable for up to 20 years.


Invasion of Gingival Epithelial Cells by Porphyromonas gingivalis.
Porphyromonas gingivalis is a major pathogen responsible for severe and chronic manifestations of periodontal disease, which is one of the most common infectious disorders of humans. Although human gingival epithelium prevents intrusions by periodontal bacteria, P. gingivalis is able to invade gingival epithelial cells. To study the dynamics and the fate of intracellular P. gingivalis, confocal laser scanning microscopy (CLSM) is a method of choice. Information gained with CLSM contains not only the number of P. gingivalis associated with gingival epithelial cells but also the bacterial localization on/inside the host cells, morphological change of host cells, and physical interaction between the bacteria and host organelle. In this chapter, we describe the protocols for microscopy techniques to morphologically study gingival epithelial cells infected by P. gingivalis.


The influence of donor characteristics on survival after heart transplantation.
With improved immunosuppressive regimens, transplantation techniques, and postoperative care, heart transplantation (HTx) has been established as a definite therapy for end-stage heart disease. Because of a donor shortage, we have accepted marginal individuals. In this study, we identified donor-related factors influencing survival after HTx by retrospective analysis of recipient data after primary HTx from February 2002 to December 2006. The Cox regression model was used to examine the effects of the following variables on survival of 112 heart transplant recipients: demographic data of gender, age, body weight, donor-recipient body weight ratio; history of smoking, alcohol drinking, diabetes mellitus, hypertension, hepatitis B surface antigen, anti-hepatitis C virus antibody; donor condication before transplantation including catecholamine doses, hypotension, cardiopulmonary resuscitation, creatine MB isoenzyme of creatine kinase (CK-MB), tropinin I, and cold ischemic time of the allograft. Catecholamines and smoking showed significant influences on HTx survival. In our series, the percentage of donors receiving inotropic support before donation was 88% (n = 99), and the percentage of donors with a history of smoking was 25% (n = 28). There was no influence of donor status of diabetes, hypertension, or hepatitis B or C infection on postoperative survival. Our results showed that inotropic support of and a history of smoking by the donor were significant factors influencing posttransplant survival.


Homonymous central quadrantanopia caused by an extrastriate (v2/v3) infarction: a case report.
A 66-year-old Taiwanese aboriginal male had complained of right-side blurred vision for 2 months, especially when reading. He had a 10-year history of hypertension and cardiovascular disease. His best-corrected visual acuity was 20/25 in each eye. Ophthalmoscopy revealed asymmetrical cupping, but a normal disc. Humphrey perimetry showed an upper homonymous paracentral quadrantanopic defect. Brain magnetic resonance imaging showed an infarction in the left lower calcarine area over the extrastriate (V2/V3) cortical area and a narrowing of the left middle and posterior cerebral arteries due to severe arteriosclerosis.


Isoenzyme specificities of immunoglobulins isolated from lactate dehydrogenase-immunoglobulin complexes.
Lactate dehydrogenase (L-lactate: NAD oxidoreductase, EC 220.127.116.11, LD) specific immunoglobulins were isolated from LD-immunoglobulin complexes in sera from 11 patients and the isoenzyme specificity of the immunoglobulins was studied by sandwich electroimmunofixation (SEIF). The immunoglobulins differed in isoenzyme specificity, depending on the heavy and/or light chains. IgA kappa recombined with LD2 and LD3, and was thought to be the antibody to common structures (H2M) in LD2 (H3M) and LD3 (H2M2). IgA kappa in a IgA/G kappa lambda case recombined with LD3-5, so that the IgA kappa might be an antibody to M2 dimer in the isoenzymes. IgA lambda recombined only with LD3, and was thought to recognize the H2M2 structure of LD3. As IgG kappa and/or lambda recombined with all LD isoenzymes of LD1-5, the immunoglobulins might react with common structures in H and M subunits. IgG lambda recombined with LD2-5, particularly with LD5, so that the IgG lambda was thought to be an antibody to the M subunit in LD2-5. From the above findings and the tetrameric structure of the LD molecule, 18 types of antibodies to different antigenic determinants on LD molecules can be theoretically derived. Each of the present 11 cases of immunoglobulin corresponded to one of the 18 types, respectively. A formula which can theoretically determine the percent LD activity recombined with immunoglobulins is described.


Inhibitory effects of Chelidonium majus extract on atopic dermatitis-like skin lesions in NC/Nga mice.
Chelidonium majus (CM) has traditionally been used for treatment of various inflammatory diseases including atopic dermatitis (AD). However its action on atopic dermatitis (AD) is unclear. Therefore, we investigated the effect of CM on AD using NC/Nga mice as an AD model. The effect of CM on 1-chloro-2,4-dinitrobenzene (DNCB) induced NC/Nga mice was evaluated by examining skin symptom severity, itching behavior, ear thickness, levels of serum immunoglobulin E (IgE), tumor necrosis factor-α (TNF-α), and interlukin-4 (IL-4), skin histology. The CM significantly reduced the total clinical severity score, itching behavior, ear thickness and the level of serum IgE in AD mouse model. CM not only decreased TNF-α but also IL-4. These results suggest that CM may be a potential therapeutic modality for AD.


Activation in primary and secondary motor areas in patients with CNS neoplasms and weakness.
To demonstrate whether cortical activation within different cortical motor regions in neurosurgical patients varies with the degree of paresis induced by mass lesions near the central region. A total of 110 patients with brain tumors infiltrating the central region and with varying degrees of paresis were investigated employing fMRI during the performance of hand motor tasks. The percent signal change between rest and activation was calculated for four cortical regions: primary motor cortex (M1), supplementary motor area, premotor area, and superior parietal lobule. Significant decreases in activation with increasing degrees of paresis were found in M1, whereas significant increases in activation were noted in secondary motor areas that were not affected by the tumor. The signal loss in areas adjacent to tumor tissue may relate either to tumor-induced changes in cerebral hemodynamics or to a direct loss of cortical neurons resulting in a lesser degree of hemodynamic changes after motor activation. The increase in activation within secondary motor areas with increasing degrees of paresis supports the growing evidence of a practice- and lesion-dependent reorganization of the cortical motor system and the ability of the brain to modulate its excitatory output according to external demands.


Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.
Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency viruses in rhesus macaques-elicited patterns of Env-antibody coevolution very similar to those in humans, including conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2 apex mode of recognition like that of human broadly neutralizing antibodies (bNAbs) PGT145 and PCT64-35S. Another rhesus antibody bound the CD4 binding site by CD4 mimicry, mirroring human bNAbs 8ANC131, CH235, and VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.


Identification of a retina-specific MEKA protein as a 33 K protein.
A photoreceptor-specific MEKA protein was purified from bovine retinal soluble fraction. The purified sample was eluted as a single peak of 74 kDa protein from a Superose column, which was dissolved into three components, MEKA protein (32 kDa), beta-(36 kDa) and gamma-(10 kDa) subunits of transducin on a SDS-PAGE. From several lines of evidence, we concluded that MEKA protein is identical with a 33k phosphoprotein reported by Lee et al (1).


Neurocognitive outcomes in pediatric brain tumors after treatment with proton versus photon radiation: a systematic review and meta-analysis.
Advances in cancer treatments, particularly the development of radiation therapy, have led to improvements in survival outcomes in children with brain tumors. However, radiation therapy is associated with significant long-term neurocognitive morbidity. The present systematic review and meta-analysis aimed to compare the neurocognitive outcomes of children and adolescents with brain tumors treated with photon radiation (XRT) or proton therapy (PBRT). A systematic search was conducted (PubMed, Embase, Cochrane, and Web of Science from inception until 02/01/2022) for studies comparing the neurocognitive outcomes of children and adolescents with brain tumors treated with XRT vs. PBRT. The pooled mean differences (expressed as Z scores) were calculated using a random effects method for those endpoints analyzed by a minimum of three studies. Totally 10 studies (n = 630 patients, average age range: 1-20 years) met the inclusion criteria. Patients who had received PBRT achieved significantly higher scores (difference in Z scores ranging from 0.29-0.75, all P < 0.05 and significant in sensitivity analyses) after treatment than those who had received XRT for most analyzed neurocognitive outcomes (i.e., intelligence quotient, verbal comprehension and perceptual reasoning indices, visual motor integration, and verbal memory). No robust significant differences (P > 0.05 in main analyses or sensitivity analyses) were found for nonverbal memory, verbal working memory and working memory index, processing speed index, or focused attention. Pediatric brain tumor patients who receive PBRT achieve significantly higher scores on most neurocognitive outcomes than those who receive XRT. Larger studies with long-term follow-ups are needed to confirm these results.


Increased rates of whole body protein synthesis and breakdown in children recovering from burns.
The rates of whole body protein synthesis and breakdown were determined, with the aid of a constant administration of [15N]glycine, during recovery in 11 acutely burned children, involving a total of 24 studies. Eleven studies were also conducted in seven healthy children before and after reconstructive surgery. Rates of whole body protein synthesis and breakdown, expressed as g protein/kg body weight/day, were significantly (p less than 0.05) and positiviely correlated with per cent body surface area total burn, per cent third-degree burn, and per cent open wound. These rates (synthesis, 7.1 +/- 2.1 g protein/kg/day; breakdown, 6.3 +/- 1.8 g protein/kg/day) were 80 to 100% greater (p less than 0.05) in patients with total burns greater than or equal to 60%, as compared to patients with less than 25% total burns or to the surgical patients. Because of the high energy cost of protein synthesis, it is proposed that an increased whole body protein turnover is partly responsible for the reported elevations in rates of heat production occurring in patients recovering from thermal injury.


Paediatric ride-on mower related injuries and plastic surgical management.
Lawnmower related injuries cause significant morbidity in children and young teenagers. The 'ride-on' mowers which are more powerful than the 'walk behind' mowers are becoming increasingly popular. The incidence and severity of injuries from either type of lawnmower appears to be steadily rising as is the burden placed on local plastic surgical and emergency services in managing the care of these patients. The aims of the study were to demonstrate changing trends in lawnmower-related injuries to children presenting to a single unit over a ten-year period and to identify any association between injury severity and machine subtype ('ride-on' versus 'walk-behind'). Hospital databases, theatre records and medical case notes were reviewed retrospectively of all patients under the age of 16 treated for lawnmower related injuries over a 10 year period from July 1998 to June 2008. Data gathered included patient demographics, injury site and severity, management (type and number of surgical procedures), length of hospital stay and outcome. Injury severity score was also calculated for each case. Controlling for estimated regional population changes, there was a significant increase in the number of ride-on mower related accidents in the time period 2003-2008, compared to the time period 1998-2003. Ride-on injuries had significantly higher injury severity scores, longer hospital stays and were more likely to involve amputations as compared with walk-behind injuries. Children can sustain significant injuries with unsafe lawnmower use. The current study demonstrates the increasing incidence of ride-on mower related injuries in children and identifies a greater morbidity associated with such injuries. Such presentations place intense demands on local plastic surgical services.


Hearing Outcomes in the Audiology Department of a Children Hospital.
The incidence of sensorineural hearing loss is between 1 and 3 per 1000 in healthy neonates and 2-4 per 100 in high-risk infants. In this study, we assessed the incidence of hearing impairment in normal term (≥ 37 wga) infants (control group), in children with suspicion and/or risk factors of hearing loss, included premature infants (< 37 weeks gestational age (wga) and/or low birth weight < 2,5 Kgr), in children diagnosed with a specific syndrome and in children with speech disorder, candidate for speech therapy. Hearing impairment is a severe consequence of prematurity and its prevalence is inversely related to the maturity of the baby based on gestation age and /or birth weight. Both above parameters are of particular importance and it has not been found that one factor prevails over the other. Premature infants have many concomitant risk factors for hearing impairment. The most important other risk factors were ototoxic medications, very low birth weight and "treatment in the intensive care unit '' (low Apgar score and mechanical ventilation). Frequent risk factors such as congenital infections and family history of hearing loss, although frequently recorded, does not seem to be very significant. Children with speech disorder do not seem to suffer from hearing impairment more frequently than children in general population.


Intellectual function in muscular dystrophies.
Intellectual function was studied in 28 boys with Duchenne dystrophy, 12 patients with facioscapulohumeral-type and 10 patients with limb-girdle-type muscular dystrophy. A definite relationship between intelligence level and the type of muscle disease was found. The more severe the genetic damage manifested by the rapidity of progression of muscular dystrophy the more definite the affection of the CNS manifesting as mental deficit. The factors influencing the level and structure of intelligence seem to exert their effect before the manifestation of muscle lesions.


The effect of casting and masticatory simulation on strain and misfit of implant-supported metal frameworks.
The influence of casting and masticatory simulation on marginal misfit and strain in multiple implant-supported prostheses was evaluated. Three-unit screw retained fixed dental prosthesis (FDP) and screw retained full-arch fixed dental prosthesis (FAFDP) frameworks were made using calcinable or overcasted cylinders on conical dental implant abutment. Four groups were obtained according to the cylinder and prosthesis type (n=10). Frameworks were casted in CoCr alloy and subjected to strain gauge analyses and marginal misfit measurements before and after 10(6) mechanical cycles (2 Hz/280 N). Results were submitted to ANOVA, Tukey's HSD and Pearson correlation test (α=0.05). No difference was found on misfit among all groups and times (p>0.05). Overcasted frameworks showed higher strain than the calcinable ones (FDP - Initial p=0.0047; Final p=0.0004; FAFDP - Initial p=0.0476; Final p=0.0115). The masticatory simulation did not influence strain (p>0.05). No correlation was observed between strain and misfit (r=0.24; p>0.05). In conclusion, the marginal misfit value in the overcasted full-arch frameworks was higher than clinical acceptable data. It proved that overcasted method is not an ideal method for full-arch prosthesis. Overcasted frameworks generate higher strain upon the system. The masticatory simulation had no influence on misfit and strain of multiple prostheses.


Seed germination and seedling development in response to submergence in tree species of the Central Amazonian floodplains.
Successful germination and seedling establishment are crucial steps for maintenance and expansion of plant populations and recovery from perturbations. Every year the Amazon River and its tributaries overflow and flood the adjacent forest, exerting a strong selective pressure on traits related to seedling recruitment. We examined seed characteristics, stored reserves, germination, seedling development and survival under water of eight representative tree species from the lower portions of the flood-level gradient to identify adaptive strategies that contribute to their regeneration in this extreme ecosystem. Submerged seedlings were assessed for longevity and survival until they showed symptoms of injury. At this point, the remaining healthy seedlings were planted in unsaturated soil to monitor recovery after re-exposure to air over 30 days. All small (seed mass ≤0.17 g) seeds had epigeal phanerocotylar-type germination, a trait that would allow plants to acquire light and CO2 in the shortest time. Cell wall storage polysaccharide was a major component of all seeds, suggesting plant investment in structural reserves. Seven of the eight species germinated and formed healthy seedlings under water that endured submersion without any apparent injury for periods of 20-115 days, depending on the species. Seedlings of some species changed the direction of root growth and grew towards the surface of the water, which might have increased the uptake of oxygen to the tissues. Only one of the seven species did not survive re-exposure to air. Species able to germinate and produce seedlings under submersion, which subsequently are able to establish in aerated soils, would have more time available for terrestrial growth. This is critical for colonization of lower portions of the flood-level gradient where establishment is constrained by the short terrestrial phase that precedes the next flood.


Depressive symptoms predict norepinephrine response to a psychological stressor task in Alzheimer's caregivers.
Increased depressive symptoms have been associated with increased basal plasma norepinephrine (NE), and may be associated with exaggerated NE response to stress. This exaggerated response may play a role in health consequences associated with caring for a loved-one with Alzheimer's disease. The current study examined the relations between the level of depressive symptoms in spousal caregivers and the physiological response to a psychological stress task. Fifty-five spousal caregivers (mean age 73 +/- 8 years) completed the depression subscale of the Brief Symptom Inventory (BSI). Plasma NE levels were assessed before and immediately after a speech stressor conducted at the caregiver's home. Hierarchical linear regression was used to determine whether caregiver depressive symptoms significantly improved prediction of change in NE levels beyond other factors theoretically and empirically related to NE. Level of depressive symptoms significantly predicted post-stressor change in NE levels (p < .01), even when controlling for age, caregiver distress, presence of caregiver hypertension, and care recipient level of cognitive function. Higher levels of depressive symptoms were associated with a greater plasma NE response to the psychological stress task. Depressive symptoms may act to exaggerate NE response to the stress of caregiving, potentially leading to an allostatic load that might predispose caregivers to negative health consequences, including cardiovascular morbidity.


Social workers' role in combating the new epidemic of type 2 diabetes in children: clinical interventions at the Hall Family Center for pediatric endocrinology and diabetes.
A variety of modalities can be employed by social work within the hospital setting to combat the phenomenon of obesity and the type 2 diabetes that it triggers in children. These issues are now plaguing our pediatric population. Social workers can provide meaningful interventions to foster needed lifestyle changes. These may include a combination of individual, family, group, and outreach medical education modalities, as well as provision of concrete services such as food stamps. Social workers are uniquely qualified to evaluate and address the underlying psychosocial stressors that may be obstacles to a child's successful adherence to recommended medical protocol. In the urban clinical setting of the Hall Family Center at Mount Sinai, offering a "menu" of flexible options has helped to engage families and motivate patients to adopt new healthy habits.


The suprachiasmatic nucleus and intergeniculate leaflet of Arvicanthis niloticus, a diurnal murid rodent from East Africa.
Little is known about the neural substrates controlling circadian rhythms in day-active compared to night-active mammals primarily because of the lack of a suitable diurnal rodent with which to address the issue. The murid rodent, Arvicanthis niloticus, was recently shown to exhibit a predominantly diurnal pattern of activity and body temperature, and may be suitable for research on the neural mechanisms underlying circadian rhythms. This paper describes, in A. niloticus, the anatomy of two neural structures that play important roles in the control of circadian rhythms, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL). Immunohistochemical techniques were used to examine the distribution of neuroactive peptides in the SCN and IGL, and retinal projections to these structures were traced with anterograde transport of the beta subunit of cholera toxin. In A. niloticus, distinct subdivisions of the SCN contained cell bodies with immunoreactive (IR) vasopressin, vasoactive intestinal polypeptide, gastrin-releasing peptide, and corticotropin-releasing factor. The SCN did not contain cell bodies with met-enkephalin-IR and substance P-IR, but did contain fibers with substance P-IR and neuropeptide Y-IR. Retinal fibers were present throughout the SCN, but were most densely concentrated along its ventral edge, particularly in the contralateral SCN. Retinal fibers also extended to a variety of hypothalamic regions outside the SCN, including the supraoptic nucleus and the subparaventricular region. The IGL contained cells with neuropeptide Y-IR and enkephalin-IR cells. Retinal fibers projected to both the ipsilateral and contralateral IGL. The anatomy of the SCN and IGL were compared and contrasted with that previously described for other nocturnal and diurnal species.


A genome-wide search for new imprinted genes in the human placenta identifies DSCAM as the first imprinted gene on chromosome 21.
We identified, through a genome-wide search for new imprinted genes in the human placenta, DSCAM (Down Syndrome Cellular Adhesion Molecule) as a paternally expressed imprinted gene. Our work revealed the presence of a Differentially Methylated Region (DMR), located within intron 1 that might regulate the imprinting in the region. This DMR showed a maternal allele methylation, compatible with its paternal expression. We showed that DSCAM is present in endothelial cells and the syncytiotrophoblast layer of the human placenta. In mouse, Dscam expression is biallelic in foetal brain and placenta excluding any possible imprinting in these tissues. This gene encodes a cellular adhesion molecule mainly known for its role in neurone development but its function in the placenta remains unclear. We report here the first imprinted gene located on human chromosome 21 with potential clinical implications.


Effects of prenatal cocaine exposure on the nigrostriatal dopamine system: an in vivo microdialysis study in the rat.
Pregnant rats were given injections of saline (0.5 ml/kg) or cocaine (10 mg/kg, 20 mg/ml, s.c.) twice daily between gestational days 7-21. Offspring were examined by microdialysis between postnatal days 10-125 to study the effects of prenatal cocaine exposure on the nigrostriatal dopamine (DA) system. Twenty-min dialysis samples were collected and assayed for DA, DOPAC and HVA. After four baseline samples, the rat was exposed to 20 min of intermittent tail pinch and monitored for four samples; then each rat received an acute injection of cocaine (20 mg/kg, i.p.) and six additional samples were collected. Basal dialysate concentrations of all DA markers, estimated from pre-implantation calibration of the probes, were markedly reduced in young rats ('pups', 10-30 days old) as compared with adult rats (40-125 days old). Compared to control pups, basal DA, as well as DOPAC and HVA, were elevated in the prenatal-cocaine pups. Tail pinch (a mild stressor) produced a significant increase in DA only in the pups prenatally exposed to cocaine. The increase in basal DA induced by an acute cocaine injection (20 mg/kg) was also greater and more prolonged in the prenatal-cocaine pups. In older rats (40-125 days) there were no group differences in any of the DA parameters. Thus prenatal exposure to cocaine produces an activation of the DA system which persists after birth but returns to normal in older rats.


Advanced nitrogen removal from landfill leachate without addition of external carbon using a novel system coupling ASBR and modified SBR.
In order to achieve advanced nitrogen removal from landfill leachate without the addition of external carbon sources, a novel system coupling an anaerobic sequencing batch reactor (ASBR) and sequencing batch reactor (SBR) was proposed for the treatment of real landfill leachate with NH4+-N and chemical oxygen demand (COD) concentrations of 1100 mg/L and 6000 mg/L, respectively. ASBR could remove 80% of the influent COD under a volumetric loading rate of 5 kg COD/(m3d). Denitritation and simultaneous nitritation-denitritation were responsible for 50% of the TN removal in SBR under alternate anoxic/aerobic modes. Furthermore, advanced nitrogen removal was realized with a total inorganic nitrogen (TIN) removal efficiency of 99% at the expense of endogenous denitritation during a 26 h period, which led to effluent COD and TN values of 550-650 mg/L and 15-25 mgN/L, respectively. For the combined system, removal efficiencies of COD and total nitrogen (TN) were above 90% and 95%, respectively.


Accumulation of chromium and zinc from aqueous solutions using water hyacinth (Eichhornia crassipes).
Under present investigation Eichhornia crassipes (water hyacinth) has been tested for removal of two important heavy metals chromium (Cr) and zinc (Zn) from metal solution. This species was grown at four concentrations of Cr and Zn, i.e. 1.0, 5.0, 10.0 and 20.0 mg l(-1) in single metal solution. This plant has performed extremely well in removing the Cr and Zn from their solution and was capable of removing up to 95% of zinc and 84% of chromium during 11 days incubation period. Removal of Cr at lower concentrations (1.0 and 5.0 mg l(-1)) was found harmless, without any symptom of toxicity but at 10.0 and 20.0 mg l(-1), plants have shown some morphological symptoms of toxicity. On the other hand E. crassipes removed Zn safely at all the four concentrations, i.e. 1.0, 5.0, 10.0 and 20.0 mg l(-1). In this case morphological symptoms of toxicity were not evident in the test plant. Biochemical parameters viz. protein, sugar and chlorophyll in experimental plants have shown a decreasing trend due to accumulation of Zn and Cr. Overall this methodology is safe for the removal of Zn and Cr and can be utilized at large scale after few further investigation.


Macrophage activation by tuftsin and muramyl-dipeptide.
Peritoneal macrophages from tuftsin or MDP-treated mice were tested for their cytostatic activity for tumor cell proliferation. Both substances are able to activate macrophages either after intravenous injection or after incubation in vitro with normal macrophages. But a stimulation as well as an inhibition of tumor cell growth can result from macrophage activation depending on the timing and dose injected. Restoration of the impaired cytostatic capacity of macrophages of mice observed with aging, is obtained by repeated administration of tuftsin. Normal and BCG-stimulated macrophages were examined for their regulatory activity on the proliferation of P815 tumor cells. Low density of macrophages per well determines a stimulation of target cell growth whether the macrophages are normal or activated. When the number of macrophages is increased, under conditions in which normal macrophages are not inhibitory. BCG-stimulated macrophages exert already a strong cytostatic activity. At high macrophage content it appears that normal macrophages can also display an inhibitory activity. Macrophage-tumor cell interactions are highly dependent on the concentration and the state of activation of macrophages.


Histidyl phosphorylation and dephosphorylation of P36 in rat liver extract.
Protein histidine kinase (Motojima, K., and Goto, S. (1993) FEBS Lett. 319, 75-79) and phosphatase in rat liver extract were characterized. The histidine kinase was recovered mostly in the membrane and the phosphatase in the soluble fraction. The kinase and its substrate 36-kDa protein (P36) were co-solubilized from the membrane under conditions in which most of the other kinases, and their substrate proteins were not solubilized. The solubilized kinase and P36 were co-eluted after high pressure liquid chromatography gel filtration, showing an apparent molecular mass of 70-75 kDa. They were also co-eluted after ion exchange chromatography. These characteristics, together with its complete resistance to genistein, indicate that the rat liver histidine kinase is not cognate to the yeast enzyme (Huang, J., Nasr, M., Kim, Y., and Matthews, H.R. (1992) J. Biol. Chem. 267, 15511-15515). The phosphatase that dephosphorylates histidyl-phosphorylated P36 was also studied using rat liver subcellular fractions and in vitro phosphorylated P36 as the substrate. The characteristics of the phosphatase, that is, 1) Mg2+ requirement for activity, 2) apparent molecular mass of 45 kDa by high performance liquid chromatography gel filtration, and 3) resistance to 100 microM okadaic acid, suggest that the primary phosphatase active in vitro is protein phosphatase 2C.


Posterior Displacement of Meniscal Ramp Lesion Is Observed on Flexed Knee Magnetic Resonance Imaging of Anterior Cruciate Ligament-Deficient Knees.
To confirm whether posterior displacement of the detached meniscocapsular structure in ramp lesions could be observed on magnetic resonance imaging (MRI) in the flexed knee position and to clarify whether this displacement on MRI is related to greater anterior knee laxity. This retrospective comparative trial study included 50 patients with anterior cruciate ligament injuries in whom attendant ramp lesions were observed on preoperative MRI. All patients underwent 3-T MRI at 120° of knee flexion preoperatively. The gap distance of the ramp lesion on sagittal slices was measured, and a distance greater than 1 mm was classified as gap positive. Additionally, joint effusion in the posteromedial recess was quantitatively evaluated by measuring the surface area of joint fluid. Prior to surgery, the side-to-side difference in anterior tibial translation (ATT) on stress radiographs at 20° of knee flexion was measured to evaluate anterior knee laxity. During anterior cruciate ligament reconstruction, the length of the ramp lesion was measured by a scale from the posteromedial portal. Of the 50 knees, 29 had ramp lesion gaps greater than 1 mm on MRI at knee flexion. The gap-positive group had a significantly greater side-to-side difference in ATT (9.6 ± 3.6 mm vs 5.0 ± 2.7 mm, P < .001) and significantly larger ramp lesion length (15.7 ± 4.9 mm vs 11.7 ± 3.9 mm, P = .002) than the gap-negative group. The gap-positive group also had a significantly greater amount of joint effusion than the gap-negative group (P < .001). Posterior displacement of the detached meniscocapsular structure in ramp lesions can be observed on MRI at knee flexion and is related to greater anterior knee laxity, lesion size, and joint effusion. Level III, retrospective comparative trial.


Naltrexone and dysphoria: a double-blind placebo controlled trial.
Naltrexone hydrochloride reportedly produces frequent dysphoria. This has led to speculation regarding the role of endorphins in the etiology of depression. Thirty-six subjects completed an 8-week trial of naltrexone or placebo with frequent mood assessments. No significant differences on POMS scales were noted for either subject group. One subject was discontinued from the study because of a severe dysphoric reaction. Naltrexone does not appear to significantly alter mood over a 2-month time course in nonaddicted, healthy individuals. Subpopulations of patients under physiological or psychological stress may react to naltrexone with dysphoric symptoms.


Phytoxicity of smelter-impacted soils in southwest Montana, USA.
A century of copper smelting in southwest Montana, USA, destroyed vegetation for many kilometers surrounding the Washoe Smelter. Once the vegetation was lost, exposed soils were subject to wind and water erosion, which removed topsoil and left soil surfaces paved with gravel. A greenhouse study was conducted using soils from smelter-impacted and non-smelter-impacted sites near Anaconda, Montana. Bluebunch wheatgrass, Agropyron spicatum (Pursh) Scribn., and western yarrow, Achillea lanulosa Nutt., were grown for 50 d in unamended, fertilized, or limed treatments to determine if soil fertility, pH, or trace elements were limiting plant growth on soil from the impacted site. The addition of fertilizer significantly increased plant biomass of both species in soils from impacted and nonimpacted sites when compared to unamended and limed soil. The addition of lime had no effect on plant growth. When plant growth in fertilized smelter-impacted soil was compared to unamended nonimpacted soil, significantly more plant biomass was observed in the fertilized smelter-impacted soil. Shoot and root concentrations of trace elements were higher in plants grown in impacted soil compared to nonimpacted soil. The only element that was found to occur in concentrations reported to be phytotoxic was arsenic (As). However, toxicity thresholds for As, reported in the literature, were generated in agricultural species and do not likely have application to the native perennials used in this study.