Allergen bronchial challenge tests: variability and reproducibility of the early response.
We evaluated allergen bronchial challenge tests (ABCTs) variability and reproducibility during 2-week intervals, respectively, in 28 and 14 Dermatophagoides pteronyssinus-sensitized patients. Increasing doses of Dpt (1.25 to 160 X 10(-3) mg) of lyophilized Dpt extract were administered at 20-minute intervals by doubling the previous dose. Dose-response curves (D-RC) were constructed for each test with the logarithm (base 2) of the allergen dose and the FEV1 in milliliters as ordinate. We analyzed different indices: the allergen doses causing a 15% decrease in FEV1 (PD15) and a 20% decrease in FEV1 (PD20), the slope of the curve beyond PD15, the overall slope, and the area under the parabolic curve. We found considerable intersubject variability in early asthmatic responses to Dpt ABCTs. Bronchoconstriction induced by allergen produced a specific D-RC for each individual. PD20 was significantly correlated with all the indices representing the whole D-RC (i.e., overall slope and area); moreover, PD20 was found on the steepest portion of the curve in 24 of 28 D-RCs. With the methodology used, we obtained a satisfactory reproducibility in a 2-week interval: the linear slope obtained by log base 2 transformation of doses was highly reproducible (p less than 0.001), as was area p under the parabolic curve. PD20 is significantly reproducible in a range of one doubling dose (twofold variation). The reproducibility of ABCTs over a short period permits solid arguments for their use in the evaluation of prophylactic treatment and in clinical research.


Ferritin as a source of iron for oxidative damage.
The generation of deleterious activated oxygen species capable of damaging DNA, lipids, and proteins requires a catalyst such as iron. Once released, ferritin iron is capable of catalyzing these reactions. Thus, agents that promote iron release may lead to increased oxidative damage. The superoxide anion formed enzymatically, radiolytically, via metal-catalyzed oxidations, or by redox cycling xenobiotics reductively mobilizes ferritin iron and promotes oxidative damage. In addition, a growing list of compounds capable of undergoing single electron oxidation/reduction reactions exemplified by paraquat, adriamycin, and alloxan have been reported to release iron from ferritin. Because the rapid removal of iron from ferritin requires reduction of the iron core, it is not surprising that the reduction potential of a compound is a primary factor that determines whether a compound will mobilize ferritin iron. The reduction potential does not, however, predict the rate of iron release. Therefore, ferritin-dependent oxidative damage may be involved in the pathogenesis of diseases where increased superoxide formation occurs and the toxicity of chemicals that increase superoxide production or have an adequate reduction potential to mobilize ferritin iron.


Impaired expression of interleukin 2 receptor and CD45RO antigen on lymphocytes from children with acute lymphoblastic leukemia in response to cytomegalovirus and varicella-zoster virus.
The expression of CD25 and CD45RO in lymphocytes from patients with acute lymphoblastic leukemia in response to cytomegalovirus and varicella-zoster virus antigens was analyzed by flow cytometry. It is suggested that the defects in the immune response to cytomegalovirus and varicella-zoster virus in patients with acute lymphoblastic leukemia on chemotherapy are in the expression of CD25 and in the switching of CD45RA cells to CD45RO cells.


Assessment of epilepsy awareness, knowledge, and attitudes among preclinical and clinical medical students in the West Bank of Palestine.
The purpose of this research was to evaluate the level of epilepsy-related awareness, knowledge, and attitude exhibited by medical students at a specific medical school in Palestine, as well as the students' reactions to the treatment and social activities provided to patients with epilepsy. A cross-sectional, observational research of 306 medical students at An-Najah National University in the West Bank, Palestine, was conducted. We used a validated survey taken from previous publications. We split the medical students into preclinical (2nd and 3rd year) and clinical (4th, 5th, and 6th year) groups to see if there were significant differences in their awareness, knowledge, attitude, and their practices toward patients with epilepsy. Several elements, such as sociodemographics, awareness, knowledge, attitude, and practices regarding epilepsy, were included in the survey. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) 29.0. Quantitative data were expressed as mean and standard deviation, whereas qualitative data as frequencies and percentages. The chi-square test was used to compare groups.Any P-value below 0.05 was considered statistically significant. In general, clinical medical students exhibited better epilepsy awareness, knowledge, and attitude than preclinical students. Of note, 73.6% of clinical students believe epilepsy is a treatable disorder, compared to 44.6% of preclinical students (P-value < 0.001). Some students believe that depression/anxiety (39.6%), psychosis (35.7%), jinns (evil spirit) (7.8%), evil eye (5.8%), and punishment from God (4.5%) cause epilepsy. Clinical students were more likely than preclinical students to have rotated in a neurology clinic or department (40% vs. 4.6%, P-value < 0.001). In total, 95.5% of clinical students and 86.9% of preclinical students (P-value = 0.006) thought patients with epilepsy should marry. Clinical stage students were more likely than preclinical stage students to think that patients with epilepsy can have children (92.7% vs. 83.1%, P-value = 0.009). Preclinical stage students were more likely than clinical stage students to believe that students with epilepsy should not play sports (22.3% versus 13%, P-value = 0.030). Generally, there were no significant gender differences in awareness, knowledge, and attitudes. The study found that medical students knew little about epilepsy types, causes, triggers, and first aid. Negative attitudes toward people with epilepsy living alone and discrimination against people with epilepsy were also observed. Students' perceptions of this prevalent disease must be improved through educational programs that provide increased opportunities for clinical exposure to this condition as well as proper inclusion of epilepsy in the regular curriculum.


Discovery of seifertite in a shocked lunar meteorite.
Many craters and thick regoliths of the moon imply that it has experienced heavy meteorite bombardments. Although the existence of a high-pressure polymorph is a stark evidence for a dynamic event, few high-pressure polymorphs are found in a lunar sample. α-PbO₂-type silica (seifertite) is an ultrahigh-pressure polymorph of silica, and is found only in a heavily shocked Martian meteorite. Here we show evidence for seifertite in a shocked lunar meteorite, Northwest Africa 4734. Cristobalite transforms to seifertite by high-pressure and -temperature condition induced by a dynamic event. Considering radio-isotopic ages determined previously, the dynamic event formed seifertite on the moon, accompanying the complete resetting of radio-isotopic ages, is ~2.7 Ga ago. Our finding allows us to infer that such intense planetary collisions occurred on the moon until at least ~2.7 Ga ago.


Mixing tannery effluent had fertilizing effect on growth, nutrient accumulation, and photosynthetic capacity of some cucurbitaceous vegetables: A little help from foe.
Tannery effluent contains a number of organic and inorganic elements as pollutants which reduce plant growth. To overcome shortage of water, use of diluted industrial wastewater such as tannery effluent can be a viable strategy for improving crop growth and yield. A pot experiment was conducted to determine the effects of tannery effluent and its various dilutions on physiological and biochemical characteristics of five cucurbitaceous vegetables. Tannery effluent was applied 0, 25, 50, 75 and 100% to 3-week-old plants of five cucurbitaceous vegetables (Cucurbita maxima, Luffa cylindrica, Citrullus vulgaris, Cucumis melo, and Praecitrullus fistulosus) for 4 weeks. Tannery effluent reduced the growth of all five cucrbitaceous vegetables. Diluted tannery effluent (25%) improved the growth of Cucurbita maxima, Citrullus vulgaris, and Cucumis melo. Moderately diluted (50%) did not affect the growth of Citrullus vulgaris and Cucumis melo. Toxic effects of tannery effluent were associated with high accumulation of heavy metals Cr, Cd, Mn, and Fe in leaves and roots. High accumulation of heavy metals in leaves reduced the accumulation of nutrients in leaves (N, P, K) and reduced photosynthetic pigments and photosynthetic rate. Changes in photosynthetic rates of all vegetable species due to tannery effluent were not associated with stomatal limitations (stomatal conductance, transpiration rate, internal CO2). Toxic effects of tannery effluent on plants also include changes in N-metabolism (amino acid and protein). However, extent of these adverse effects of tannery effluent on vegetables was species specific. It is suggested that Cucurbita maxima can be grown by supplying 25% tannery effluent, whereas Citrullus vulgaris and Cucumis melo can be grown with moderately diluted (50%) tannery effluent.


Potential synergistic effect of Alhagi graecorum ethanolic extract with two conventional food preservatives against some foodborne pathogens.
The present study aims to screen the anti-bacterial activity and synergistic interaction of A. graecorum Boiss. ethanolic extract with two food preservatives against five strains of foodborne bacteria. Disk diffusion and minimum inhibitory concentration were used for anti-bacterial assay, checkerboard assay and time-kill curve were used for the combination studies. HPLC analysis and molecular docking study were performed to corroborate the in vitro results. The ethanolic extract showed anti-bacterial activity against all tested bacterial strains with inhibition zones from 7.5 to 9.3 mm and MIC values ranged between 1.2 and 1.8 mg mL-1. The combination of the ethanolic extract with Na-benzoate or Na-propionate resulted in synergistic and additive interactions against the tested bacteria with fractional inhibitory concentration index (FICI) ranges 0.31-0.63 and no antagonism was shown. Time-kill curve assay showed that the synergistic and additive combinations have inhibitory effects on the tested strains. The ethanolic extract combination with Na-benzoate or Na-propionate can be used for development new sources of food preservatives. Testing new different natural plant extracts with food preservatives will help develop new anti-bacterial agents.


Autism: processing of novel auditory information assessed by event-related brain potentials.
Event-related brain potentials (ERPs) of 13-21-year-old autistic subjects and age-matched controls were elicited by auditory stimuli in a variation of orienting response paradigms. Unexpected, novel sounds (bizarre concoctions of human, mechanical and computer sounds) were randomly inserted as probes in a sequence of expected, non-novel sounds (the word 'me'). In order to help ensure that both subject groups were attending to this stream of information, each subject was required to press a button to a specified target sound (the word 'you') also randomly inserted in the sequence of expected non-novel sounds. The ERP results showed that in both groups, unexpected, novel probes and also targets evoked a different neurophysiological response than did expected, non-novel sounds. This suggests that the autistic group did not misperceive novel information as non-novel and were able to make simple classification decisions as accurately as normal controls. However, in the autistic group, there may be less 'processing' of the novel probes and of targets: compared to the control group, the autistic group had smaller amplitudes of two long-latency components to novels and smaller P3b amplitudes to targets. The two components to novels were termed A/Pcz/300 (A = auditory; P = positive; cz = electrode site of maximum amplitude; 300 = latency in msec) and A/Ncz/800. In another sequence of sounds, subjects simply listened to frequently presented 'me' sounds (90%) and infrequently presented 'you' sounds (10%). In this no-task condition, no differences between autistic and normal control subjects were found.


Robotic Light Touch Assists Human Balance Control During Maximum Forward Reaching.
We investigated how light interpersonal touch (IPT) provided by a robotic system supports human individuals performing a challenging balance task compared to IPT provided by a human partner. IPT augments the control of body balance in contact receivers without a provision of mechanical body weight support. The nature of the processes governing the social haptic interaction, whether they are predominantly reactive or predictive, is uncertain. Ten healthy adult individuals performed maximum forward reaching (MFR) without visual feedback while standing upright. We evaluated their control of reaching behavior and of body balance during IPT provided by either another human individual or by a robotic system in two alternative control modes (reactive vs. predictive). Reaching amplitude was not altered by any condition but all IPT conditions showed reduced body sway in the MFR end-state. Changes in reaching behavior under robotic IPT conditions, such as lower speed and straighter direction, were linked to reduced body sway. An Index of Performance expressed a potential trade-off between speed and accuracy with lower bitrate in the IPT conditions. The robotic IPT system was as supportive as human IPT. Robotic IPT seemed to afford more specific adjustments in the human contact receiver, such as trading reduced speed for increased accuracy, to meet the intrinsic demands and constraints of the robotic system or the demands of the social context when in contact with a human contact provider.


[Device related infections. How to identify and how to treat].
Because of the enormous increase in pacemaker and implantable cardioverter-defibrillator (ICD) implants, the number of device-related infections has also increased considerably. In fact, this increase has been out of proportion due to the higher patient age at implant, the increased co-morbidity of patients and the higher complexity of the implanted devices. Apart from few exceptions the infection of a pacemaker or ICD requires complete explantation of the whole system with adjunctive antibiotic therapy. The diagnosis of device infection, the indication and different options for therapy are thoroughly discussed in this article according to the current status of knowledge.


Significance of coronary artery tone in patients with vasospastic angina.
To investigate the relation between basal coronary artery diameter and development of coronary artery spasm, the diameters of the proximal, middle and distal segments of the three major coronary artery branches, together with that of the left main trunk, were measured on a control angiogram and after ergonovine and nitrate administration in 30 patients with vasospastic angina without significant organic stenosis, and in 35 patients without ischemic heart disease. The percent change in coronary diameter after ergonovine and nitrate administration compared with the control diameter was used as an index of coronary vasoreactivity. In patients with vasospastic angina, coronary artery responses to both ergonovine and nitrate were greater in the spastic segments than in the other segments (p less than 0.05), and those of the coronary arteries without spasm were greater than those of the coronary arteries in patients without ischemic heart disease (p less than 0.01). There were no significant differences between the coronary artery diameters in the two groups after nitrate administration, and the control diameters were less in patients with vasospastic angina than in patients without ischemic heart disease. These observations indicate that a coronary vasomotion disorder, which involves increased basal coronary artery tone and hypersensitivity to vasoconstrictive stimuli, not only at a localized segment but also in the entire coronary artery tree, is present in patients with vasospastic angina. Clinically, evaluation of basal coronary artery tone may be useful for predicting the occurrence and location of coronary artery spasm.


Functional and oncological outcomes of limb-salvage surgery for foot and ankle tumors.
Limb-salvage surgery has become the backbone treatment for musculoskeletal tumors in the last decades. However, limb-salvage with safe margins for tumors of the foot and ankle is challenging, due to the complex anatomy of this region. This study aimed to evaluate functional and oncological outcomes, complications, and local recurrence of limb-salvage procedures for tumors of the foot and ankle. This study was a retrospective review of 18 patients with primary tumors of the foot and ankle who underwent limb-salvage surgery between 1996 and 2015, with a minimum follow-up of 2 years. Clinical presentations, radiological and histopathological investigations, surgical procedures, functional and oncological outcomes, complications and local recurrences were analyzed. The Musculoskeletal Tumor Society (MSTS) scoring system was utilized for evaluation of the functional outcome. With a mean follow-up period of 44.2 months, 7 males and 11 females with a mean age of 29.2 years were included. Nine patients were presented as recurrent cases. The most common location was forefoot in 7 patients. Synovial sarcoma was the histopathologic diagnosis in 7 patients. The final surgical margins were wide in 15 patients, wide-contaminated in one patient, and marginal in two patients. After resection, soft tissue reconstruction and wound coverage were done by soft tissue flaps in 4 patients. The mean MSTS score was 27.5. Four patients developed local recurrence, all of them were recurrent cases. Limb-salvage surgery for foot and ankle tumors is an effective treatment option with good functional outcome. Level IV, retrospective case series.


Urinary kidney injury molecule-1 in renal disease.
Kidney injury molecule-1 (KIM-1), a type l transmembrane glycoprotein, is recognized as a potential biomarker for detection of tubular injury in the main renal diseases. Urinary KIM-1 increases rapidly upon the tubular injury, and its levels are associated with the degree of tubular injury, interstitial fibrosis, and inflammation in the injured kidney. Currently, the investigation of kidney diseases is usually performed through the assessment of serum creatinine and urinary albumin. However, these biomarkers are limited for the early detection of changes in renal function. Besides, the tubular injury appears to precede glomerular damage in the pathophysiology of renal diseases. For these reasons, the search for sensitive, specific and non-invasive biomarkers is of interest. Therefore, the purpose of this article is to review the physiological mechanisms of KIM-1, as well to present clinical evidence about the association between elevated urinary KIM-1 levels and the main renal diseases such as chronic kidney disease, diabetic kidney disease, acute kidney injury, and IgA nephropathy.


IFN-γ synergism with poly I:C reduces growth of murine and human cancer cells with simultaneous changes in cell cycle and immune checkpoint proteins.
Previously, we reported that IFN-γ and poly I:C, a TLR3 Pattern Recognition Receptor (PRR) agonist, reduces growth of and induces Cleaved-Caspase-3, ISG54 and p27Kip in B16 melanoma cells. Here, analysis of IFN-γ/PRR synergism was expanded with UM-SCC1 and UM-SCC38 human squamous carcinoma cells and other PRR agonists. As in B16 cells, poly I:C plus IFN-γ synergism reduced UM-SCC1 and UM-SCC38 growth, and no more than 24 h was needed for significant growth reduction. IFN-γ synergism to stem B16 growth also occurred with TLR7, TLR9, TLR4, and STING agonists, but not TLR2 agonist. IFN-γ synergized with TLR3 and TLR4 agonists reducing UM-SCC1 growth, and with TLR7 and TLR3 agonists reducing UM-SCC38 growth. IFN-γ plus poly I:C, which had the most pronounced effect, decreased cyclin-D1, increased G1 cell cycle arrest, and increased Cleaved caspase-3 in B16 cells, as well as RAW264.7, a virus-transformed murine macrophage cell line. Finally, IFN-γ plus poly I:C modulated total but not cell surface expression of immune checkpoint protein PD-L1, as well as cell cycle checkpoint proteins in B16 cells. Thus IFN-γ plus poly I:C, and other PRR agonists, may well be effective adjuvants to cancer immunotherapy against several tumor cell types.


Effect of combined oral estrogen/progestogen preparation (Kliogest) on bone mineral density, plasma lipids and postmenopausal symptoms in HRT-naïve Thai women.
Kliogest is commonly prescribed for the relief of acute postmenopausal symptoms and prevention of postmenopausal bone loss. However, there have been few data on its effect in Asian women. This 1-year, single-center, randomized, double-blind and placebo-controlled study evaluated the efficacy and safety of Kliogest in hormone replacement therapy (HRT)-naïve Thai women. The subjects were 120 healthy Thai women aged between 45 and 65 years, with intact uterus, and who had been amenorrheic for at least 1 year. Kliogest increased spine (+ 6%, p < 0.01) and hip (+2%, p < 0.01) bone mineral density (BMD), and lowered plasma total cholesterol (TC) (-16%, p < 0.05) and low density lipoprotein cholesterol (LDL-C) (-16%, p < 0.05) concentrations. However, Kliogest also resulted in a decrease in high density lipoprotein cholesterol (HDL-C) concentration (-18%, p < 0.05). Compared to placebo, the reduction in menopausal symptoms by Kliogest was not statistically significant. The frequency and severity of treatment-related uterine bleeding decreased with the duration of Kliogest treatment. Furthermore, there was a fairly strong relationship between the change in serum estrone concentration and the average monthly weighted bleeding scores over the first 6 months (Spearman's correlation r = 0.54; p < 0.001), which became weaker over the entire treatment period (Spearman's correlation r = 0.27; p < 0.01). Although there was a small to moderate relationship between baseline estrone concentration and both lumbar (r = 0.23, p < 0.02) and hip (r = 0.20, p < 0.05) BMD, there was no significant relationship between Kliogest-induced change in estrone concentration and change in lumbar and hip BMD. Continuous treatment with Kliogest for 1 year reversed the potential postmenopausal bone loss in HRT-naïve Thai postmenopausal women. However, its effect on cardiovascular risk is uncertain. Furthermore, Kliogest is safe but appears to have no significant effect on climacteric symptoms in the patients in the present study.


Development and validation of derivatization-based LC-MS/MS method for quantification of short-chain fatty acids in human, rat, and mouse plasma.
Short-chain fatty acids (SCFAs), the end products of gut microbial fermentation of dietary fibers and non-digestible polysaccharides, act as a link between the microbiome, immune system, and inflammatory processes. The importance of accurately quantifying SCFAs in plasma has recently emerged to understand their biological role. In this work, a sensitive and reproducible LC-MS/MS method is reported for SCFAs quantification in three different matrices such as human, rat and mouse plasma via derivatization, using as derivatizing agent O-benzylhydroxylamine (O-BHA), coupled with liquid-liquid extraction. First, the instrumental parameters of the mass spectrometer and then the chromatographic conditions were optimized using previously SCFAs derivatives synthetized and used as standards. After that, the best conditions for derivatization and extraction from plasma were studied and a series of determinations were performed on human, rat, and mouse plasma aliquots to validate the overall method (derivatization, extraction, and LC-MS/MS determination). The method showed good performance in terms of recovery (> 80%), precision (RSD <14%), accuracy (RE < ± 10%) and sensitivity (LOQ of 0.01 µM for acetic, butyric, propionic and isobutyric acid) in all plasma samples. The method thus developed and validated was applied to the quantification of major SCFAs in adult and aged mice, germ-free mice and in germ-free recipient mice subjected to fecal transplant from adult and aged donors. Results highlighted how plasma concentrations of SCFAs are correlated with age further highlighting the importance of developing a method that is reliable for the quantification of SCFAs to study their biological role.


[Earstructures in one case of anencephalie (author's transl)].
According to the majority of cases under observation the following anomalies could be found: extended, separated or manifold developed crura of the stapes, reduction in the circular windings of the cochlea down to 1 1/2 with a normal development of Corti's organum, reduction of the nerve structures of the nervus cochlearis to a munimum and an open facial canal.


Antihypertensive effect of passion fruit peel extract and its major bioactive components following acute supplementation in spontaneously hypertensive rats.
Extracts from leaves, peels or flowers of Passiflora are noted for their medicinal effects. Passiflora edulis peel extract (PFPE) has been proposed to lower blood pressure (BP); however, only indirect measurement techniques have been employed. To more accurately measure the effect of PFPE on hemodynamic parameters and determine the minimal effective dose, hemodynamic parameters were directly measured in spontaneously hypertensive rats (SHR) implanted with radiotelemeters. PFPE was given orally at 0, 2.5, 50 or 200 mg/kg body weight (BW) to determine the minimal effective dose. Once this dose was determined, the potential active components, edulilic acid (EA), anthocyanin fraction (AF) or γ-aminobutyric acid (GABA), were tested to determine which may contribute to the reductions in BP. The 50 mg PFPE/kg BW dose was the lowest dose that significantly reduced all hemodynamic parameters from baseline when compared to control. When the potential actives were provided at equivalent doses to those found in 50 mg PFPE/kg BW, the EA and AF significantly reduced all measured hemodynamic parameters from baseline when compared to control. GABA did not significantly affect any hemodynamic parameters compared to control and significantly increased heart rate. These direct measurements indicate that PFPE can decrease hemodynamic parameters in SHR and indicate that EA and AF are active compounds that contribute to the antihypertensive effects of PFPE supplementation. While these results are encouraging, detailed mechanistic studies are needed to determine the putative value of PFPE for blood pressure control in humans.


The use of 'artificial saliva' as a neutral control condition in gustatory research: Artificial saliva is not a neutral gustatory stimulus.
Distilled water with NaHCO3 and KCl is a solution often referred to as 'artificial saliva' because its chemical composition mimics human saliva. It is often used as a control stimulus in gustatory research, especially in neuroimaging, owing to the claim that it does not produce a response in primary gustatory cortex Yet evidence that human research volunteers perceive this liquid as affectively neutral is lacking. Unpublished data from our lab suggested that this solution might be perceived as aversive. This study set out to systematically test the parameters influencing taste neutrality. We used two different concentrations of distilled water with NaHCO3 and KCl, as well as bottled water as a control stimulus. Healthy adults rated all stimuli on two separate scales to rule out an interpretation based on the specifics of a single scale. Our participants rated artificial saliva as aversive on both scales. The bottled water was rated as neutral in valence on both scales, and as significantly less intense in sensation than both concentrations of the artificial saliva. This is the first study to have directly tested the subjective feelings that accompany the ingestion of these oft-used solutions on a trial-by-trial basis. We found that these stimuli, which were previously assumed to be neutral, may not be perceived as such by research participants. Therefore, future gustatory studies should take care when using this solution as a neutral baseline. It is advised that trial-by-trial ratings are collected. Also, depending on the nature of future studies, bottled water may be considered as a preferable neutral baseline.


T2 mapping in myocardial disease: a comprehensive review.
Cardiovascular magnetic resonance (CMR) is considered the gold standard imaging modality for myocardial tissue characterization. Elevated transverse relaxation time (T2) is specific for increased myocardial water content, increased free water, and is used as an index of myocardial edema. The strengths of quantitative T2 mapping lie in the accurate characterization of myocardial edema, and the early detection of reversible myocardial disease without the use of contrast agents or ionizing radiation. Quantitative T2 mapping overcomes the limitations of T2-weighted imaging for reliable assessment of diffuse myocardial edema and can be used to diagnose, stage, and monitor myocardial injury. Strong evidence supports the clinical use of T2 mapping in acute myocardial infarction, myocarditis, heart transplant rejection, and dilated cardiomyopathy. Accumulating data support the utility of T2 mapping for the assessment of other cardiomyopathies, rheumatologic conditions with cardiac involvement, and monitoring for cancer therapy-related cardiac injury. Importantly, elevated T2 relaxation time may be the first sign of myocardial injury in many diseases and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. This comprehensive review discusses the technical considerations and clinical roles of myocardial T2 mapping with an emphasis on expanding the impact of this unique, noninvasive tissue parameter.


Sensitivity of biopsy site in evaluating regression of gastric atrophy after Helicobacter pylori eradication treatment.
Helicobacter pylori infection is a major cause of the progress of gastric glandular atrophy, a high-risk background factor in the development of gastric cancer. Regression of gastric atrophy is critical to prevention of cancer by H. pylori eradication treatment. However, it is controversial whether gastric atrophy regresses after H. pylori eradication. To determine the most sensitive and appropriate biopsy site for evaluation of regression of atrophy after treatment. Thirty-eight patients who showed regression of gastric atrophy in histology after treatment were investigated. Four biopsy specimens from the lesser and greater curvatures in the antrum and corpus were evaluated before and after treatment according to the Updated Sydney System. Regression of atrophy after treatment was seen in 30 of 38 biopsy specimens from the lesser curvature of the corpus (79%), and this site was most sensitive. Odds ratio of this site to the others was 8.28. Regression of atrophy in this site was observed at 12.2 months in the younger patients and 15.9 months in the elder patients. Biopsy sampling from the lesser curvature of the corpus is the most sensitive and appropriate for evaluation of regression of gastric atrophy after H. pylori eradication treatment.


Superiority of 18F-FDG PET compared to 111In-labelled leucocyte scintigraphy in the evaluation of fever of unknown origin.
To compare the accuracy of positron emission tomography (PET) using (18)F-FDG (Fluorodeoxyglucose) PET with (111)In-labelled leucocytes scintigraphy (LS) in patients with fever of unknown origin (FUO). Twenty-three consecutive patients with FUO were prospectively studied using whole-body LS and PET. Performance of the two modalities for identifying a cause of FUO was evaluated. Final diagnosis was based on biopsy, microbiological tests, clinical and imaging follow-up. Abnormal tracer uptake was seen in 3/23(13%) and 14/23(61%) patients on LS and PET respectively, suggesting a higher sensitivity (p < 0.01) for the latter. All LS positive cases were identified on PET and confirmed as infection. The causes of FUO in the other PET positive patients were: infection (n = 3), vasculitis (n = 3), non-infectious inflammatory conditions (n = 2) and cancer (n = 1). No specific diagnosis was reached in 2 patients. Of 13 patients without a definite diagnosis following PET and LS, 10 made a spontaneous recovery during the follow-up period and no definite cause for FUO was found on investigation. Still's disease, Polymyalgia rheumatica and Chronic fatigue syndrome/Myalgic encephalomyelitis were diagnosed in the remaining three patients during follow-up. The results thus showed an overall sensitivity of 86% for PET and 20% for LS (p < 0.01). The overall specificity for FDG PET was 78% as against 100% for LS. PET had a PPV of 86% and a NPV of 78% whereas LS had a PPV of 100% and a NPV of 40%. PET has a higher sensitivity than LS in identifying the aetiology of FUO. PET/PET-CT, where available, should be used as the non-invasive investigation of choice in the assessment of patients with FUO.


Comparison of SPE, IFE, and FLC in Monitoring Patients with Multiple Myeloma After Autologous Stem Cell Transplantation.
Conventionally, serum protein electrophoresis (SPE) and serum immunofixation electrophoresis (IFE) are used as primary methods to diagnose and monitor multiple myeloma (MM). Recently, serum-free light chain (FLC) assay has been incorporated into hematological screening programs for myeloma. The purpose of this study is to compare the performance of the three methods in monitoring MM patients after autologous stem cell transplantation (ASCT). SPE, serum IFE and serum FLC assay were performed on 38 MM patients who underwent ASCT. In total, four patients had unexpected protein bands (UPBs) and 13 patients had relapsed after ASCT. Our results indicate that IFE is more sensitive than SPE and FLC assay in detection of UPBs and relapse. The results of IFE may provide useful information in advance of patient relapse.


NAD in muscle of man at rest and during exercise.
NAD can be used to assess the adequacy of oxygen availability to the respiratory chain. An enzymatic assay was established for NAD in human muscle biopsy samples. It gave reliable, reproducible results. The variation within and between subjects was less than 12%. Muscle NAD and lactate were determined at rest, and after bicycle ergometry work requiring approximately 75 and approximately 100% VO2 max (six subjects, four tests each). A positive (P less than 0.01) linear relationship between resting muscle NAD and percent slow twitch fibers was found, suggesting that fiber types may have different NAD content. Muscle NAD decreased during submaximal and maximal work (P less than 0.05). A large portion (73%) of the NAD reduction could be accounted for by increased muscle water. No relationship could be established between NAD and lactate. The negative linear relationship (P less than 0.01) between the muscle/blood ratio and percent slow twitch fibers is another indication of the fiber having different metabolic responses to the activity.


The effect of methaqualone on prenatal development in the rat.
Methaqualone treatment of pregnant rats in doses of 100-200 mg/kg day produces resorption and a series of anomalies whose incidence increases with the dose-level employed.


Left atrial strain correlates with severity of cardiac involvement in Anderson-Fabry disease.
Cardiac involvement in Anderson-Fabry disease (AFD) results in myocardial lipid depositions. An early diagnosis can maximize therapeutic benefit. Thus, this study aims to investigate the potential of cardiac MRI (CMR) based parameters of left atrial (LA) function and strain to detect early stages of AFD. Patients (n = 58, age 40 (29-51) years, 31 female) with genetically proven AFD had undergone CMR including left ventricular (LV) volumetry, mass index (LVMi), T1, and late gadolinium enhancement, complemented by LA and LV strain measurements and atrial emptying fractions. Patients were stratified into three disease phases and compared to age and sex-matched healthy controls (HC, n = 58, age 41 [26-56] years, 31 female). A total of 19 early-, 20 intermediate-, and 19 advanced-phase patients were included. LV and LA reservoir strain was significantly impaired in all AFD phases, including early disease (both p < 0.001). In contrast, LA volumetry, T1, and LVMi showed no significant differences between the early phase and HC (p > 0.05). In the intermediate phase, LVMi and T1 demonstrated significant differences. In advanced phase, all parameters except active emptying fractions differed significantly from HC. ROC curve analyses of early disease phases revealed superior diagnostic confidence for the LA reservoir strain (AUC 0.88, sensitivity 89%, specificity 75%) over the LV strain (AUC 0.82). LA reservoir strain showed impairment in early AFD and significantly correlated with disease severity. The novel approach performed better in identifying early disease than the established approach using LVMi and T1. Further studies are needed to evaluate whether these results justify earlier initiation of therapy and help minimize cardiac complications. • Parameters of left atrial function and deformation showed impairments in the early stages of Anderson-Fabry disease and correlated significantly with the severity of Anderson-Fabry disease. • Left atrial reservoir strain performed superior to ventricular strain in detecting early myocardial involvement in Anderson-Fabry disease and improved diagnostic accuracies of approaches already using ventricular strain. • Further studies are needed to evaluate whether earlier initiation of enzyme replacement therapy based on these results can help minimize cardiac complications from Anderson-Fabry disease.


Real-time three-dimensional echocardiographic evaluation of left ventricular systolic synchronicity in patients with chronic heart failure: comparison with tissue Doppler imaging.
To investigate the clinical value of real-time three-dimensional echocardiography (RT-3DE) for assessing of left ventricular systolic synchronicity. Thirty healthy volunteers and 62 patients with congestive heart failure (CHF) were enrolled. The SD of time to peak systolic motion (TDI-Ts12-SD) was measured with tissue Doppler imaging in 12 myocardial segments. The SD and maximal difference of the time to minimal systolic volume (Tmsv) between 16, 12, or 6 myocardial segments, expressed as a percentage of cardiac cycle duration, were measured with RT-3DE and labeled Tmsv16-SD%, Tmsv12-SD%, Tmsv6-SD%, Tmsv16-D%, Tmsv12-D%, and Tmsv6-D%, respectively. The Spearman coefficient and Kappa value were calculated, and Bland-Altman analysis was performed to investigate the correlation and agreement between the two methods. Tmsv values were compared with ejection fraction (EF). There was a moderately positive (p< 0.01) correlation between TDI-Ts12-SD and Tmsv16-SD%, Tmsv12-SD%, Tmsv16-D%, and Tmsv12-D% (r = 0.65, 0.64, and 0.65, respectively, with Kappa values of 0.66, 0.65, 0.72, and 0.74, respectively, p< 0.01). Tmsv16-SD%, Tmsv12-SD%, and Tmsv12-D% were significantly different between CHF patients with EF ≤ 35% and those with EF > 35%. RT-3DE can be used in patients with CHF to quantify left ventricular mechanical dyssynchrony. Tmsv12-SD% and Tmsv12-D% were the best indices of left ventricular systolic synchronicity in relation to the severity of CHF as evaluated from EF.


Cyclophosphamide hemorrhagic cystitis requiring urinary diversion.
Hemorrhagic cystitis secondary to cyclophosphamide is a well recognized and unique urologic complication of this widely used agent. Cessation of the drug and supportive care are usually sufficient for management but refractory cases are difficult to treat and potentially life-threatening. A review of the pathology and treatment of this disorder is presented with specific reference to a patient requiring urinary diversion.


Robust Analysis of Phylogenetic Tree Space.
Phylogenetic analyses often produce large numbers of trees. Mapping trees' distribution in "tree space" can illuminate the behavior and performance of search strategies, reveal distinct clusters of optimal trees, and expose differences between different data sources or phylogenetic methods-but the high-dimensional spaces defined by metric distances are necessarily distorted when represented in fewer dimensions. Here, I explore the consequences of this transformation in phylogenetic search results from 128 morphological data sets, using stratigraphic congruence-a complementary aspect of tree similarity-to evaluate the utility of low-dimensional mappings. I find that phylogenetic similarities between cladograms are most accurately depicted in tree spaces derived from information-theoretic tree distances or the quartet distance. Robinson-Foulds tree spaces exhibit prominent distortions and often fail to group trees according to phylogenetic similarity, whereas the strong influence of tree shape on the Kendall-Colijn distance makes its tree space unsuitable for many purposes. Distances mapped into two or even three dimensions often display little correspondence with true distances, which can lead to profound misrepresentation of clustering structure. Without explicit testing, one cannot be confident that a tree space mapping faithfully represents the true distribution of trees, nor that visually evident structure is valid. My recommendations for tree space validation and visualization are implemented in a new graphical user interface in the "TreeDist" R package. [Multidimensional scaling; phylogenetic software; tree distance metrics; treespace projections.].


A family with combined mutations of the hemophilia A and X-linked adrenoleukodystrophy genes.
X-linked adrenoleukodystrophy and hemophilia A are two distinct, potentially devastating, genetic diseases whose corresponding genes are located in close proximity on the X chromosome. Here we report a family with members affected with both conditions, only the second such family ever reported. Although a structural genomic rearrangement involving both genes was initially predicted to underlie this extremely rare phenotype, genotyping revealed the unlikely occurrence of two individual point mutations. Given the impact of this result on the heritability of the two disorders within the family, this case illustrates the significance of performing detailed molecular analysis in patients with multiple genetic disorders.


Social anxiety and social comparison: differential links with restrictive and bulimic attitudes among nonclinical women.
This study investigated the relationship of two social psychological constructs (social anxiety and social comparison) with bulimic and restrictive eating attitudes among nonclinical women. Eighty young women completed a measure of social anxiety (the Fear of Negative Evaluation Scale, FNE), a measure of social comparison (the Iowa-Netherlands Comparison Orientation Measure, INCOM), the Beck Depression Inventory (BDI), and the Eating Disorders Inventory (EDI). The results indicate a differential link between the two different social processes and the nature of eating psychopathology. Specifically, heightened social anxiety predicted drive for thinness, while levels of social comparison predicted bulimic attitudes. The findings support a model where the two social processes are each associated with different patterns of eating pathology.


A review of genus Eumegacetes Looss, 1900 (Eumegacetidae), with description of species from the Egyptian house sparrow: Passer d. niloticus.
Genus Eumegacetes is briefly reviewed E. (Anterovitellum) sp. is described from Passer domesticus niloticus caught from Sharkiya Governorate, North Delta, which represents the first host and new locality. A key is proposed to differentiate the three species of the genus known so far from Egypt.


Oxidative modifications of mitochondria complex II.
Increased superoxide (O2 (·-)) and nitric oxide (NO) production is a key mechanism of mitochondrial dysfunction in myocardial ischemia/reperfusion injury. In the complex II, oxidative impairment, decreased protein S-glutathionylation, and increased protein tyrosine nitration at the 70 kDa subunit occur in the post-ischemic myocardium (Zhang et al., Biochemistry 49:2529-2539, 2010; Chen et al., J Biol Chem 283:27991-28003, 2008; Chen et al., J Biol Chem 282: 32640-32654, 2007). To gain the deeper insights into ROS-mediated oxidative modifications relevant in myocardial infarction, isolated complex II is subjected to in vitro oxidative modifications with GSSG (to induce cysteine S-glutathionylation) or OONO(-) (to induce tyrosine nitration). Here, we describe the protocol to characterize the specific oxidative modifications at the 70 kDa subunit by nano-LC/MS/MS analysis. We further demonstrate the cellular oxidative modification with protein nitration/S-glutathionylation with immunofluorescence microscopy using the antibodies against 3-nitrotyrosine/glutathione and complex II 70 kDa polypeptide (AbGSC90) in myocytes under conditions of oxidative stress.


Relationship between income generating activities of rural women and their reproductive health behavior in Bangladesh.
The objective of the study was to find out the effects of income generating activities of rural women and their reproductive health behavior (contraceptive use) in Bangladesh. A cross-sectional study using a multi-stage sampling technique was carried out among 200 married rural women in Cox's Bazar, Bangladesh. Data were collected using a structured questionnaire on socioeconomic factors, income generating activities, women's empowerment in mobility, decision making and reproductive health behavior in terms of contraceptive use, number of children and desire for more children. Logistic regression analysis was used to determine the relationship between income generating activities and contraceptive use. Almost half (45.5%) of the participants were involved in income generating activities. A great majority (63.9%) worked year-round, two-thirds (75.0%) earned cash for their family and 21.3% were engaged in poultry farms. Women aged 26-35 years, members of any non-governmental organization and from a poor family were more likely to be engaged in income generating activities (≤0.001). Highly educated women worked more than their less educated counterparts and the opposite was true for their husbands (≤0.001). Almost half of the women (45.0%) did not use any contraceptive. Contraceptive use was significantly higher among working women (73.4%) than with non-working women (33.0%). Women engaged in income generating activities were more likely to use contraceptives compared to non-working women (odds ratio 5.6, 95% confidence interval 3.1-7.0, ≤0.001). Income generating activities seem to empower women, increase their likelihood of using contraception and are one of the key issues for changing the life of rural women in Bangladesh.


Utility of Cardiopulmonary Exercise Test in Mitral Valve Transcatheter Edge-to-Edge Repair.
The growing utility of mitral valve transcatheter edge-to-edge repair (TEER) for minimally invasive treatment of severe mitral regurgitation has seen an attendant need to identify patients that can best benefit from this treatment. To ensure that the most appropriate patients are selected for the percutaneous procedure, cardiopulmonary exercise testing (CPET) had been incorporated into our centre's workflow for patients undergoing evaluation for mitral TEER. CPET can be a useful diagnostic and prognostic tool in the management of patients with severe MR undergoing percutaneous valve repair, especially when complemented with appropriately timed echocardiographic examinations, and should be integrated as a part of all percutaneous MV TEER programs as a standard investigation pre- and post-intervention.


Elevated blood drug levels obtained from indwelling silicon catheters during oral cyclosporine A administration.
Cyclosporine A (CsA) may be bound to and released from the inner surface of central venous catheters resulting in spuriously elevated blood drug levels. We observed this phenomenon in a boy transplanted because of aplastic anemia up to 9 weeks after CsA had been switched from intravenous to oral administration. In comparison to phlebotomy, simultaneous blood sampling from the double lumen catheter resulted in a greater than 10-fold, or two-fold increase in drug levels, respectively, depending on whether or not the line used for prior CsA infusion was selected. Thus, prolonged binding of CsA to the inner surface of venous catheters should also be considered during oral administration.


Selenium supranutrition: are the potential benefits of chemoprevention outweighed by the promotion of diabetes and insulin resistance?
Selenium was considered a toxin until 1957, when this mineral was shown to be essential in the prevention of necrotic liver damage in rats. The hypothesis of selenium chemoprevention is principally formulated by the observations that cancer incidence is inversely associated with selenium status. However, recent clinical and epidemiological studies demonstrate a role for some selenoproteins in exacerbating or promoting other disease states, specifically type 2 diabetes, although other data support a role of selenium in stimulating insulin sensitivity. Therefore, it is clear that our understanding in the role of selenium in glucose metabolism and chemoprevention is inadequate and incomplete. Research exploring the role of selenium in individual healthcare is of upmost importance and possibly will help explain how selenium is a double-edged sword in the pathologies of chronic diseases.


Treatment outcome and prognostic factors of adult glioblastoma multiforme.
This study aimed to report the characteristics, prognostic factors and treatment outcome of 223 patients with glioblastoma multiforme (GBM). This retrospective study was carried out by reviewing the medical records of 223 adult patients diagnosed at a tertiary academic hospital between 1990 and 2008. Patients' follow up ranged from 1 to 69 months (median 11 months). Surgery was attempted in all patients in whom complete resection in 15 patients (7%), subtotal resection in 77 patients (34%), partial resection in 73 patients (33%) and biopsy alone in 58 patients (26%) were done. In addition, we performed a literature review of PubMed to find out and analyze major related series. In all, we collected and analyzed the data of 33 major series including more than 11,000 patients with GBM. There were 141 men and 82 women. The median progression free- and overall survival were 6 (95% CI=5.711-8.289) and 11 (95% CI=9.304-12.696) months respectively. In univariate analysis for overall survival, age (P=0.003), tumor size (P<0.013), performance status (P<0.001), the extent of surgical resection (P=0.009), dose of radiation (P<0.001), and adjuvant chemotherapy (P<0.001) were prognostic factors. However, in multivariate analysis, only radiation dose, extent of surgical resection, and adjuvant chemotherapy were independent prognostic factors for overall survival. The prognosis of adult patients with GBM remains poor; however, complete surgical resection and adjuvant treatments improve progression-free and overall survival.


Adaptation of cholesterol-requiring NS0 mouse myeloma cells to high density growth in a fully defined protein-free and cholesterol-free culture medium.
NS0 has been used as a fusion partner for the production of hybridomas and has more recently been engineered to produce recombinant protein. A protein-free culture medium, designated W38 medium, has previously been developed which supported high density growth of rat myeloma and hybridoma cell lines. NS0 cells failed to grow in W38 medium and in a number of protein-free culture media which support the growth of other myeloma cell lines. NS0 cells are derived from the NS-1 cell line, which is known to require exogencus cholesterol. It was found that NS0 cells grew in W38 medium supplemented with phosphatidylcholine, cholesterol, and albumin and that NS0 were auxotrophic for cholesterol. Protein-free growth of NS0 cells was achieved by using β-cyclodextrin to replace albumin as a lipid carrier. The maximal cell density reached in this protein-free medium was in excess of 1.5×10(6) cell ml(-1). The lipid supplements in the medium precipitated after a few days storage at +4°C. In order to overcome this problem a protocol was developed which allowed NS0 cells to be adapted to cholesterol-independent growth in W38 medium. NS0.CF (cholesterol-independent NS0 cells) were cultured continuously in W38 medium for several months. In shake flask culture a cell density of 2.4×10(6) cells ml(-1) was achieved in W38 medium compared with 1.41×10(6) cells ml(-1) in RPMI 1640 medium containing 10% foetal bovine serum. NS0.CF cells readily grew in a 1 litre stirred bioreactor using W38 medium supplemented with Pluronic F68 reaching a density of 3.24×10(6) cells ml(-1). NS0.CF were cloned protein-free by limiting dilution in W38 medium, giving colonies in wells that were seeded at an average density of 0.32 cells per 200 μl. This study has demonstrated for the first time the growth of a cholesterol-requiring mouse myeloma cell line in a completely defined protein-free medium and its subsequent adaptation to cholesterol-independence.


Extrapolation of praziquantel pharmacokinetics to a pediatric population: a cautionary tale.
L-praziquantel (PZQ) pharmacokinetic data were analyzed from two relative bioavailability Phase 1 studies in adult, healthy subjects with two new oral dispersion tablet (ODT) formulations of L-PZQ administered under various combinations of co-administration with food, water, and/or crushing. Linear mixed effects models adequately characterized the noncompartmental estimates of the pharmacokinetic profiles in both studies. Dose, food, and formulation were found to significantly affect L-PZQ exposure in both studies. The model for AUC was then extrapolated to children 2-5 years old accounting for enzyme maturation and weight. The predicted exposures were compared to an external Phase 1 study conducted by the Swiss Tropical and Public Health Institute using a currently marketed formulation (Cesol 600 mg immediate-release tablets) and found to be substantially lower than observed. A root cause analysis was completed to identify the reason for failure of the models. Various scenarios were proposed and tested. Two possible reasons for the failure were identified. One reason was that the model did not account for the reduced hepatic clearance seen in patients compared to the healthy volunteer population used to build the model. The second possible reason was that PZQ absorption appears sensitive to meal composition and the model did not account for differences in meals between a standardized Phase 1 unit and clinical sites in Africa. Further studies are needed to confirm our hypotheses.


Lipoxygenase metabolites of arachidonic acid do not induce mucus secretion from rabbit intestinal goblet cells in vitro.
Lipoxygenase metabolites of arachidonic acid are effective mucus secretagogues in the respiratory tract but their efficacy in the intestinal tract was unknown. Mucosal explants and sheets of epithelial cells isolated from rabbit small and large intestine were exposed to leukotrienes B4, C4, and D4 and monohydroxyeicosatetraenoic acids 5-HETE, 12-HETE, and 15-HETE. Light and electron microscopic inspection of goblet cells in treated tissues failed to detect evidence of recent compound exocytosis of mucin granules or other morphological evidence of secretory activity. These results indicate that lipoxygenase metabolites are not directly responsible for the increased mucus secretion observed in ulcerative colitis.


Effect of donor kidney morphology parameters on the prognosis in living kidney transplantation recipients.
The effect of donor kidney morphology parameters on the prognosis of renal transplant recipients remains unclear. We conducted a retrospective cohort study consisting of 290 pairs of donors and recipients who underwent living related renal transplantation in our center between December 2013 and December 2015. The donor kidney morphology parameters, demographic characteristics and renal function of the included participants were collected and analyzed. The univariate linear regression analysis revealed that the donor kidney weight (DKW)/recipient body weight (RBW), DKW/recipient body surface area (RBSA), DKW/recipient body mass index (RBMI), donor kidney volume (DKV)/RBW, DKV/RBSA, DKV/RBMI, and donor body weight (DBW)/RBW were significantly correlated with estimated glomerular filtration rate (eGFR) and serum creatinine in recipients within two years of transplantation. In our multivariate linear regression analysis, DKW/RBW and donor age significantly correlated with eGFR at 6, 12, 18 and 24 months after transplantation. DKW/RBW had the best prediction performance for good renal allograft function at 12 months after transplantation. We found that when the age of the donor was 55 years and above, the prediction performance of the nephron dosing to the recipient's metabolic demands mismatch was elevated. After grouping according to the donor's age and DKW/RBW, the allograft function from different donor ages improved as DKW/RBW increased. The number of recipients who were rejected in the high DKW/RBW group was significantly fewer than those in the low and medium groups the 1, 2, and 3-year graft and patient survival rates were comparable among these groups. Furthermore, we also identified that when the age of the donor was 55 years and above, the threshold of DKW/RBW was 3.09 g/kg via the receiver operating characteristic curve, which predicted a good renal function 12 months after transplantation. The donor kidney morphology parameters were significantly associated with early renal allograft function, especially when the age of the donor was 55 years and above.


Impact of PECS tablet computer app on receptive identification of pictures given a verbal stimulus.
The purpose of this brief report was to determine the effect on receptive identification of photos of a tablet computer-based augmentative and alternative communication (AAC) system with voice output. A multiple baseline single-case experimental design across vocabulary words was implemented. One participant, a preschool-aged boy with autism and little intelligible verbal language, was included in the study. Although a functional relation between the intervention and the dependent variable was not established, the intervention did appear to result in mild improvement for two of the three vocabulary words selected. The authors recommend further investigations of the collateral impacts of AAC on skills other than expressive language.


Transcriptional signatures related to glucose and lipid metabolism predict treatment response to the tumor necrosis factor antagonist infliximab in patients with treatment-resistant depression.
The tumor necrosis factor (TNF) antagonist infliximab was recently found to reduce depressive symptoms in patients with increased baseline inflammation as reflected by a plasma C-reactive protein concentration >5 mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined in peripheral blood mononuclear cells from infliximab responders (n=13) versus non-responders (n=14) compared to placebo at baseline and 6 h, 24 h, and 2 weeks after the first infliximab infusion. Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. One-hundred-forty-eight gene transcripts were significantly associated (1.2-fold, adjusted p≤0.01) with response to infliximab and were distinct from placebo responders. Transcripts predictive of infliximab response were associated with gluconeogenesis and cholesterol transport, and were enriched in a network regulated by hepatocyte nuclear factor (HNF)4-alpha, a transcription factor involved in gluconeogenesis and cholesterol and lipid homeostasis. Of the 148 transcripts differentially expressed at baseline, 48% were significantly regulated over time in infliximab responders, including genes related to gluconeogenesis and the HNF4-alpha network, indicating that these predictive genes were responsive to infliximab. Responders also demonstrated inhibition of genes related to apoptosis through TNF signaling at 6 h and 24 h after infusion. Transcripts down-regulated in responders 2 weeks after infliximab were related to innate immune signaling and nuclear factor-kappa B. Thus, baseline transcriptional signatures reflective of alterations in glucose and lipid metabolism predicted antidepressant response to infliximab, and infliximab response involved regulation of metabolic genes and inhibition of genes related to innate immune activation.


Mitochondrial aconitase suppresses immunity by modulating oxaloacetate and the mitochondrial unfolded protein response.
Accumulating evidence indicates that mitochondria play crucial roles in immunity. However, the role of the mitochondrial Krebs cycle in immunity remains largely unknown, in particular at the organism level. Here we show that mitochondrial aconitase, ACO-2, a Krebs cycle enzyme that catalyzes the conversion of citrate to isocitrate, inhibits immunity against pathogenic bacteria in C. elegans. We find that the genetic inhibition of aco-2 decreases the level of oxaloacetate. This increases the mitochondrial unfolded protein response, subsequently upregulating the transcription factor ATFS-1, which contributes to enhanced immunity against pathogenic bacteria. We show that the genetic inhibition of mammalian ACO2 increases immunity against pathogenic bacteria by modulating the mitochondrial unfolded protein response and oxaloacetate levels in cultured cells. Because mitochondrial aconitase is highly conserved across phyla, a therapeutic strategy targeting ACO2 may eventually help properly control immunity in humans.


First detection of Chlamydia avium in healthy Amazon parrots (Amazona aestiva) in Argentina.
In recent years, new Chlamydia species, other than Chlamydia psittaci, have been confirmed in birds. One of these new species, Chlamydia avium, was reported mainly in pigeons and parrots in Europe. Analyzing multimucosal swabs obtained from 7 Amazon parrots (Amazona aestiva) from illegal trade and admitted to the Reserva Experimental Horco Molle (Tucuman, Argentina) for their rehabilitation, we describe the finding of the genetic material of C. avium in 2 of these birds. There were no signs compatible with the chlamydiosis-like disease in the studied birds or in the rehabilitation center staff. The use of sensitive and wide-ranging molecular tools is necessary for the detection of all Chlamydiaceae present in birds and would aid in the selection of control measures in wildlife rehabilitation centers to prevent outbreaks in the facilities and the introduction of pathogens in nature. We provide the first molecular evidence of the presence of C. avium in Argentina and a new species of psittacine host.


The role of nitric oxide in systemic and hepatic haemodynamics in the rat in vivo.
The physiological role of nitric oxide (NO) in portal venous and hepatic arterial haemodynamics in the rat in vivo during healthy and diseased conditions remains unclear. The present study determined the physiological role of nitric oxide in hepatic haemodynamics in the rat in vivo during healthy conditions as a basis for future pharmacological work. Male Wistar rats (300-350 g) were anaesthetised with fentany/fluanisone (0.3 mg/kg s.c.) and midazolam (0.3 mg/kg s.c.) and heparinised (30 U/100 g i.v.) via a cannulated left carotid artery for measurement of heart rate, mean arterial pressure, and the difference between systolic and diastolic blood pressures (P(S-D)). Following laparotomy, two distal ileocolic veins were cannulated, one catheter introduced to a distance of 1 cm and used for intraportal drug injections and the other to the main trunk of the portal vein for continuous measurement of portal venous pressure. The portal venous trunk and hepatic artery were carefully isolated and electromagnetic probes placed around each of them for measurement of portal venous flow and hepatic arterial flow. Augmentation of NO production was achieved by intraportal injection of 0.2, 0.4, 0.6 and 0.8 g/kg L-arginine and the NO donor, 3-morpholinosydnonimine (SIN-1), was injected intraportally at 0.2, 0.4, 0.6 and 0.8 mg/kg. L-NAME, the non-selective NOS inhibitor, was injected intraportally in increasing doses of 5, 10, 15 and 20 mg/kg in the absence or presence of L-arginine in doses of 0.2 and 0.5 g/kg. L-arginine increased portal blood flow by 25% without significant changes in systemic haemodynamics. SIN-1 decreased mean arterial pressure by 33% with no effect on portal blood flow. Both L-arginine and SIN-1 reduced portal venous pressure by 25% in a dose-dependent manner. L-NAME had no effect on portal haemodynamics despite a significant increase in systemic arterial pressure of 60% that was reduced dose-dependently by L-arginine. Hepatic arterial flow increased by 88% and 49% at the second and third doses of L-arginine and by 68% and 27% at the first two doses of L-NAME. No significant changes in hepatic arterial flow were found when L-NAME and L-arginine were given together. It is concluded that augmented endogenous NO production increased portal flow. Inhibition of endogenous NO had no effect on portal haemodynamics. Endogenous NO may not play a major role in regulation of portal haemodynamics in the rat in vivo.


SWAP-MEAT Athlete (study with appetizing plant-food, meat eating alternatives trial) - investigating the impact of three different diets on recreational athletic performance: a randomized crossover trial.
Plant-based diets are known to be beneficial for cardiovascular health and promote environmental sustainability. However, many athletes avoid plant-based diets due to concerns of protein inadequacy. To investigate the impact of two predominately plant-based diets-whole food plant-based (WFPB) and plant-based meat alternatives (PBMA)-vs. an omnivorous diet, favoring red meat and poultry (Animal), on endurance and muscular strength. 12 recreational runners and 12 resistance trainers were assigned to three diets-WFPB, PBMA, and Animal-for 4 weeks each, in random order. Primary outcomes for runners (12-minute timed run) and resistance trainers (composite machine strength) were collected at baseline and after diets, along with secondary performance outcomes and dietary data. 22 recreational athletes completed the study (age: 26.2 ± 4.4 years; sex: 10 female, 12 male; BMI: 23.1 ± 2.4 kg/m2). Mean differences in 12-minute timed run - WFPB vs. Animal (- 23.4 m; 95% CI: - 107 to 60.0 m) and PBMA vs. Animal (- 2.9 m; 95% CI: - 119 to 113 m) - were not significant. Mean percent differences in composite machine strength - WFPB vs. Animal (- 2.7%; 95% CI: - 5.8 to 0.4% and PBMA vs. Animal (- 0.7%; 95% CI: - 3.5 to 2.2%) - were not significant. Average protein intake for all diets met International Society for Sports Nutrition recommendations. Our findings suggest recreational athletes can maintain athletic performance on both an omnivorous diet and two diets that are predominately plant-based. NCT05472701. Retrospectively registered.


Phenytoin and carbamazepine: differential effects on cognitive function.
This review summarizes the studies on the cognitive side-effects of two important antiepileptic drugs: phenytoin and carbamazepine. A large literature database was compiled through the DIMDI computer database and the inspection of recent reviews. Only scientific articles published in peer-reviewed journals during the last 25 years were selected. Of the 358 potentially relevant papers on cognitive effects of AEDs, a total of 16 studies have been found that have studied both carbamazepine and phenytoin. After excluding studies with designs that do not permit valid inferences regarding the cognitive effects of AEDs, only five studies remained. The evaluation of these studies reveal that our current knowledge allows us to draw conclusions about the cognitive side-effects of phenytoin and carbamazepine only with great caution. The claim in reviews that 'both drugs have an impact on cognitive function, PHT to a larger degree than CBZ' is simply not supported by valid 'high quality' data. The same is true for the overall conclusion in more recent reviews that 'drug-induced cognitive effects of these AEDs on cognitive function are probably mild or even negligible'. Apparently, the only information that we have is that the differential impact of PHT and CBZ on cognitive function is not extremely different. No conclusive and reconfirmed data are available on the absolute effects of CBZ and PHT (differences between the two drugs and a no-treatment condition). Our review summarizes some recommendations for future studies.


Urethral Complications Post-Holmium Laser Enucleation of the Prostate: A Seven-Year Experience.
Background: Urethral strictures (US) and bladder neck contracture (BNC) are troublesome complications of transurethral surgery. We aimed to report the incidence, risk factors, and management of US and BNC post-holmium laser enucleation of the prostate (HoLEP) together with review of literature. Patients and Methods: A retrospective review of prospectively managed HoLEP patients in one institution between 2015 and 2021 was performed. The study included patients with complete follow-up of at least 1-year. Multivariate regression analysis for risk factors of US or BNC was performed. Appropriate statistical analysis methods were used. Results: Out of total 1055 HoLEP patients, 566 patients were included. Eleven (1.94%), 8 (1.41%), and 1 (0.17%) patients developed US, BNC, and both, respectively, while 8 (1.41%) patients had postoperative recurrence of intraoperatively diagnosed US. With multivariate regression analysis, intraoperative US (p = 0.0055, odds ratio [OR] = 15.5, confidence interval [95% CI] = 2.2-37.7), intraoperative need for meatotomy (p = 0.0019, OR = 7.69, 95% CI = 2.12-27.8), and longer operative time (p = 0.0250, OR = 1.043, 95% CI = 1.005-1.083) were predictors of US/BNC. For US patients, urethral dilatation under local anesthesia was sufficient in 14 (70%) patients while 6 (30%) patients had visual urethrotomy. Patients with BNC were managed by endoscopic bladder neck incision. Conclusion: Although the US/BNC are annoying long-term sequalae that may complicate HoLEP, the incidence is still low and can be easily managed. Diagnosed intraoperative stricture, need for meatotomy, and longer operative time are the main predictors of urethral complications post-HoLEP.


Identification of four novel mutations in the thyroid hormone receptor-β gene in 164 Spanish and 2 Greek patients with resistance to thyroid hormone.
The aim of the study was to describe the clinical, biochemical, and genetic features of a sample of Mediterranean patients with RTH (resistance to thyroid hormone) due to mutations in TRβ (thyroid hormone receptor beta) referred to our institution during the last 15 years. 166 blood samples were received for RTH genetic testing between January 1997 and December 2011. Genetic testing was performed by PCR amplification followed by sequencing of exons 7, 8, 9, and 10. Clinical and biochemical features were obtained from available information sent by referring hospitals. Mutations were identified in 50 patients (29 probands and 21 relatives). 64% were women, and mean ± stdev age at diagnosis among probands was 33.2 ± 20.5 years. The following clinical features were recorded: goiter in 50%, hyperkinetic behavior in 32%, and tachycardia in 29%. Up to 19% of the probands had undergone some type of thyroidal ablative therapy before diagnosis. As for biochemical features, mean ± stdev TSH was 10.2 ± 21.4 mUI/L, and mean ± stdev fT4 was 35.5 ± 10.8 pmol/L. We found four new mutations: p.Phe451Leu, p.Pro452Arg, p.Glu457Gly, and p.Phe459Leu. The clinical and biochemical characteristics of our samples of Mediterranean populations with RTH were similar to those described in the published literature. Interestingly, in our populations we have identified four novel mutations in the TRβ gene.


III6NeuAcLc4Cer in human SW1116 colorectal carcinoma cells: a possible oncofetal antigen that is not dependent on Lewis gene expression.
Monospecific rabbit antibodies directed against the human milk sialyloligosaccharides III6NeuAcLcOse4 (sialyltetrasaccharide b), IV3NeuAcLcOse4 (sialyltetrasaccharide a), and IV6NeuAcnLc4Ose (sialyltetrasaccharide c) were used to detect their homologous haptens as gangliosides or ganglioside-derived sialyloligosaccharides from the human colorectal carcinoma cell line SW1116. III6NeuAcLc4Cer was first detected in human meconium [P. A. Prieto and D. F. Smith (1985) Arch. Biochem. Biophys. 241, 281-289], and its presence in a total ganglioside fraction of SW1116 cells together with its absence from a total lipid extract of normal human intestinal mucosa are consistent with III6NeuAcLc4Cer being a tumor-associated oncofetal antigen. IV3NeuAcLc4Cer, a ganglioside in human meconium [P. A. Prieto and D. F. Smith (1986) Arch. Biochem. Biophys. 249, 243-253], was also detected in SW1116 cells; an observation that is consistent with its being the immediate precursor to the sialyl-Lea ganglioside in SW1116 cells. Specific antisera against sialylated type 1 oligosaccharide chains whose expression is independent of the Lewis gene fucosyltransferase may be useful diagnostic reagents for oncofetal, carbohydrate antigens.


The correlation between proteoglycan 2 and neuropsychiatric systemic lupus erythematosus.
The proposed pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) mainly includes ischemia and neuroinflammation mechanisms. Protein encoded by Proteoglycan 2 (PRG2) mRNA is involved in the immune process related to eosinophils, also being found in the placenta and peripheral blood of pregnant women. We evaluated the correlation between PRG2 and NPSLE for the first time and found that PRG2 protein was overexpressed in the serum of patients with NPSLE and correlated with the SLE disease activity index (SLEDAI) subset scores of psychosis. Moreover, we investigated the correlation between hippocampal PRG2 level and hippocampally dependent learning and memory ability in MRL/lpr mice, and discovered that the number of PRG2+GFAP+ astrocytes in the cortex and hypothalamus and the number of PRG2+IBA-1+ microglia in the hippocampus and cortex significantly increased in the MRL/lpr mice. These data provided a reference for the follow-up exploration of the role of PRG2 in SLE or other diseases.


Molecular Modelling of Optical Biosensor Phosphorene-Thioguanine for Optimal Drug Delivery in Leukemia Treatment.
Thioguanine is an anti-cancer drug used for the treatment of leukemia. However, thioguanine has weak aqueous solubility and low biocompatibility, which limits its performance in the treatment of cancer. In the present work, these inadequacies were targeted using density functional theory-based simulations. Three stable configurations were obtained for the adsorption of thioguanine molecules on the phosphorene surface, with adsorption energies in the range of -76.99 to -38.69 kJ/mol, indicating physisorption of the drug on the phosphorene surface. The calculated bandgap energies of the individual and combined geometries of phosphorene and thioguanine were 0.97 eV, 2.81 eV and 0.91 eV, respectively. Owing to the physisorption of the drug molecule on the phosphorene surface, the bandgap energy of the material had a direct impact on optical conductivity, which was significantly altered. All parameters that determine the potential ability for drug delivery were calculated, such as the dipole moment, chemical hardness, chemical softness, chemical potential, and electrophilicity index. The higher dipole moment (1.74 D) of the phosphorene-thioguanine complex reflects its higher biodegradability, with no adverse physiological effects.


Antifungal activity of a novel compound from Burkholderia cepacia against plant pathogenic fungi.
To investigate antifungal activity of a novel compound (named as CF66I provisionally) against plant pathogenic fungi, mainly including Fusarium sp., Colletotrichum lindemuthianum, Rhizoctonia solani, etc. Minimal inhibition concentrations (MIC) and minimal fungicidal concentrations (MFC) of CF66I for each fungi were determined using serial broth dilution method. The data demonstrated MIC ranged from 2.5 to 20.0 microg ml(-1) and MFC were shown at levels of < or =7.5 microg ml(-1) except Fusarium sp. With reverse microscopy, profound morphological alterations of fungal cells were observed after exposure to CF66I. Conidiospores were completely inhibited, and protoplasm aggregated to form chalamydospores because of the changes of cell permeability. Some chalamydospores were broken, suggesting the compound probably possessed strong ability of damaging the cell wall. In addition, CF66I was investigated for its antifungal stability against Curvularia lunata. The results showed CF66I kept strong fungi-static activity over-wide pH range (pH 4-9) and temperature range (from -70 to 120 degrees C). The compound CF66I exhibited strong and stable broad-spectrum antifungal activity, and had a significant fungicidal effect on fungal cells. Results from prebiocontrol evaluations performed to date are probably useful in the search for alternative approaches to controlling serious plant pathogens.


Casey House: interpreting the location of a Toronto AIDS hospice.
This paper focuses on an overtly geographical issue, the introduction of a housing facility for people living with AIDS (PLWAs) into the urban landscape. Specifically, we critically analyze the location of Casey House, an AIDS hospice in Toronto and presently the only facility of its kind in Canada. Three questions are addressed: (i) how did Casey House come to exist?; (ii) why is Casey House located at the corner of Huntly Street and Isabella Street?; and (iii) will Casey House be reproduced? In our response to the first two questions, we draw selectively upon three perspectives (accessibility, structuralist and humanistic) that have been appealed to in analyses of (controversial) health care facility location processes. In the concluding discussion, three relevant spheres of reproduction are considered: locational, institutional and social. In consideration of the obvious constraints on reproduction, we conclude that the creation and location of Casey House may well be a unique geographical event in Canada.


Suprathreshold contrast perception in functional amblyopia.
Three experiments were conducted to investigate suprathreshold contrast perception of a group of strabismic and anisometropic amblyopes. In the first experiment, simple reaction-time was measured as a function of the contrast of sinusoidal gratings. At all contrast levels, the amblyopic eyes showed prolonged reaction-times compared to the non-amblyopic eyes. In the second experiment, the perceived contrast of suprathreshold sinusoidal gratings was measured using an interocular successive matching paradigm. The third experiment compared perceived contrast of the amblyopic and non-amblyopic eye by contrast magnitude estimation. The results of the matching and magnitude estimation experiments showed that while amblyopic observers show large losses of contrast sensitivity at threshold, at suprathreshold contrast levels perceived contrast is essentially normal or near normal in the amblyopic eye. Taken together, these experiments suggest that: 1) the amblyopic eye has a higher contrast gain than the non-amblyopic eye, and 2) the amblyopic eye shows prolonged response latencies. Similar results can be obtained in normal observers under conditions of peripheral viewing and noise masking.


Urinary alpha1-microglobulin excretion as biomarker of renal toxicity in trichloroethylene-exposed persons.
Concern on human renal toxicity and carcinogenicity of trichloroethylene is based on findings of increased incidences of renal cell cancers in persons with long-lasting and high occupational exposures to this solvent. The full tumour development is likely to require promotional stimuli, by repetitive episodes of high peak exposures to trichloroethylene, leading to nephrotoxicity. This process is visualised by the excretion of tubular marker proteins in the urine of exposed persons. For this purpose, surveillance of alpha1-microglobulin excretion is being suggested by the Deutsche Forschungsgemeinschaft. The present study assessed the applicability of alpha1-microglobulin as a biomarker of proximal tubule damage in the prevention of nephrotoxicity by trichloroethylene exposures. For this purpose, alpha1-microglobulin excretions were assessed in trichloroethylene-exposed and non-exposed subgroups of both cases (diseased with renal cancer) and controls (not diseased with renal cancer) of a recent case-control study. The median of alpha1-microglobulin excretions in non-exposed persons was below the detection limit, but it was clearly elevated in exposed persons. The Wilcoxon rank sum test showed a significant difference ( P=0.0090). Consistent with the underlying concept, renal cell cancer cases who had been exposed to trichloroethylene had higher alpha1-microglobulin excretions than non-exposed cases ( P=0.0005) and also had higher alpha1-microglobulin excretions than exposed controls ( P=0.0004). Of 20 trichloroethylene-exposed renal cell cancer cases only three (15%) displayed a normal alpha1-microglobulin excretion of <5 mg/l. By contrast, 41 (52%) out of 79 non-exposed renal cancer cases showed normal excretions of the biomarker. The present data are in agreement with the concept of pathogenesis of renal cell cancers developing under high (suggested: >500 ppm peak exposures) and long-term (several years) exposure to trichloroethylene. They also visualise the potential value of alpha1-microglobulin excretion as a routine biomarker of renal toxicity that may be used in the medical surveillance of trichloroethylene-exposed persons.


Mullerianosis of the urinary bladder: report of a case with suggested metaplastic origin.
Mullerianosis of the urinary bladder is a very rare and morphologically complex tumor-like lesion. It is composed of several types of mullerian-type lesions, including endometriosis, endocervicosis, and endosalpingiosis. This disease occurs in women of the reproductive age group. In the pathogenesis, implantative and metaplastic origins have been suggested, and they are still under discussion. In the present report, a rare case of this lesion in a 41-year-old woman is described. The bladder contained, in addition to typical mullerianosis, glandular cystitis with focal intestinal metaplasia. An interesting and, to our knowledge, hitherto unreported feature was a rare continuity between the glands of mullerianosis and glands of glandular cystitis. The histologic and immunohistochemical findings in the present case support strongly the metaplastic origin of mullerianosis.


Apical ventricular septal defects: follow-up concerning anatomic and surgical considerations.
Apical ventricular septal defects (VSDs) are difficult to visualize and close transatrially. We described their distinctive anatomic features, which have seldom been documented angiocardiographically and pathologically, in order to develop an effective approach for their surgical management. Fourteen postmortem cases, two explanted hearts, 9 successfully operated patients, and 1 unoperated living patient were included in this report. Angiocardiographic documentation of the apical VSD was available in 14 of 16 (87.5%) of the postmortem and transplanted cases, and in 6 of 10 (60%) of the living patients. Echocardiograms were available in 23 of all 26 cases (88%). Severe associated malformations were present in 14 of 16 (87%) of the pathologically documented cases. Large VSDs allowed extensive communication between the left ventricular and the right ventricular sinuses in 4 patients. In 12 of the pathologically documented cases and in the 10 living patients, the left ventricular apex communicated with the right ventricular apical infundibular recess. Extremely large apical VSDs with severe biventricular dysplasia and dysfunction may require cardiac transplantation. Large apical VSDs can be successfully closed through a small apical infundibulotomy. This approach, applicable even in small infants, can avoid pulmonary artery banding or left ventriculotomy.


Synthesis of oxetane and azetidine ethers as ester isosteres by Brønsted acid catalysed alkylation of alcohols with 3-aryl-oxetanols and 3-aryl-azetidinols.
Oxetanes and azetidines continue to draw significant interest in medicinal chemistry, as small, polar and non-planar motifs. Oxetanes also represent interesting surrogates for carbonyl-containing functional groups. Here we report a synthesis of 3,3-disubstituted oxetane- and azetidine-ethers, with comparisons made to the ester functional group. The tertiary benzylic alcohols of the 4-membered rings are selectively activated using Brønsted acid catalysis and reacted with simple alcohols to form the ethers and maintain the oxetane ring intact. This approach avoids the use of strong bases and halide alkylating agents and allows alcohol libraries to be leveraged. Oxetane ethers demonstrate excellent chemical stability across a range of conditions and an improved stability vis-à-vis analogous esters under basic and reducing conditions.


Nutrition and lifestyle intervention in type 2 diabetes: pilot study in the Netherlands showing improved glucose control and reduction in glucose lowering medication.
Prevalence of type 2 diabetes (T2D) is increasing rapidly and lifestyle interventions to reverse diabetes are seen as a possible solution to stop this trend. New practice-based evidence is needed to gain more insight in the actual, and above all scientific, basis for these claims. This observational study with a pretest post-test design aimed to pilot a 6-month multicomponent outpatient group-based nutrition and lifestyle intervention programme on glycaemic control and use of glucose lowering medication in motivated T2D patients with a body mass index (BMI) >25 kg/m2 in the Netherlands (February 2015-March 2016). 74 T2D patients (56% female) aged 57.4±8.0 years with mean BMI 31.2±4.2 kg/m2 and mean waist circumference 105.4±10.2 cm were included in the study. Compared with baseline, mean HbA1c levels at 6 months were 5 mmol/mol lower (SD=10, p<0.001) and the number of participants with HbA1c levels ≤53 mmol/mol after intervention had increased (from 36% (n=26/72) to 60% (n=43/72)). At baseline, 90% of participants were taking at least one type of glucose lowering medication. At 6 months, 49% (n=35/72) of the participants had reduced their medication or eliminated it completely (13%). Secondary outcomes were significantly lower fasting glucose levels (- 1.2±2.6 mmol/L), body weight (-4.9±5.1 kg), BMI (-1.70±1.69 kg/m2) and waist circumference (-9.4±5.0 cm). Plasma lipids remained unchanged except for a decrease in triglyceride levels. Furthermore, self-reported quality of life was significantly higher while experienced fatigue and sleep problems were significantly lower. This pilot study showed that a 6-month multicomponent group-based program in a routine care setting could improve glycaemic control and reduce the use of glucose lowering medication in motivated T2D diabetics. A fully scaled study is needed to confirm these results.


Audio-spatial deficits in humans: differential effects associated with left versus right hemisphere parietal damage.
In order to study auditory spatial localization in subjects with posterior damage involving the parietal lobe, we investigated their manual pointing performances to linguistic and white noise signals distributed over six sound sources situated in the anterior auditory field at ear level. The results showed: (1) A striking difference between patterns of deficits associated with right and left damage. In subjects with right damage, auditory localization deficits occurred in the horizontal plane, were manifested as restrictions in the peripheral left auditory hemifield and tended to be related to left visual neglect. In subjects with left damage, auditory localization deficits occurred in the entire auditory field in the horizontal as well as vertical planes, and they were particularly strong in the antero-frontal region. (2) One subject with right damage and visual neglect but no left auditory spatial restriction, showed deficits in the right hemifield where sound source location tended to be overestimated. This subject also showed a better discrimination of the origin of a white noise than of a linguistic signal. Results are discussed in terms of hemispheric asymmetries of function.


Soil carbon pool and dynamics of different fractions in subalpine temperate coniferous forests of Western Himalaya, India.
Natural forests have the ability to sequester atmospheric carbon for a long time and fix it into the soil through a variety of processes such as decomposition and root respiration. The changing environment of alpine forests alters the characteristics of soil carbon, causing it to be divided into several components. The current study looked at soil carbon fractions and how they changed over time, both annually and seasonally, at different depths and along an altitudinal gradient. Seasonal sampling was carried out at three depths, with standard procedures employed to estimate the results of soil carbon fractions. The results showed that the surface layer (10 cm) had the highest value of all soil qualities such as SOC, Fraction I, Fraction II, Fraction III, SOM and active pool of carbon than the subsurface (20 cm and 30 cm) layers with autumn dominating the seasons. Site 1 had the highest value and Site 4 lowest, indicating that altitudinal variance had a direct relationship with distinct soil fractions. On an annual basis, the corresponding soil carbon fraction variation was examined, revealing the maximum retention capability at 30 cm of depth. According to the findings, the soils of the Western Himalayas have a high potential for carbon sequestration and conversion into various fractions, with significant annual and seasonal change due to changing environmental conditions.


IFN-α-mediated Base Excision Repair Pathway Correlates with Antiviral Response Against Hepatitis B Virus Infection.
Previous studies identified APOBEC deaminases as enzymes targeting hepatitis B virus (HBV) DNA in the nucleus thus affecting its persistence. Interferon (IFN)-α treated chimpanzees and hepatitis C patients showed elevated APOBEC expression. We thus hypothesized that the responses to IFN-α treatment of chronic hepatitis B (CHB) patients is influenced by IFN-induced base excision repair (BER). CHB-treatment naïve patients, patients treated with PEGylated IFN-α, and patients with sequential treatment of Entecavior and PEGylated IFN-α were recruited. Blood and liver biopsy samples were collected before treatment and at treatment endpoint. BER genes were assessed by quantitative RT-PCR. BER gene expression levels and IFN treatment responses were correlated in patient liver biopsies. APOBEC3A, -B, -C, -D/E, and-G mRNA levels were up-regulated in IFN-treated patients. APOBEC3A expression was significantly higher in IFN-responders than in non-responders. BER genes NEIL3 was down-regulated in IFN-treated patients. APOBEC3 and BER gene expression at treatment endpoints partially correlated with the corresponding absolute DNA level or degree of HBsAg and HBV DNA decline. Our study suggests that the expression of APOBEC3A positively correlates with IFN-treatment responses in CHB patients, while NEIL3 shows negative correlation. These genes may involve to IFN mediated viral suppression and serve as biomarkers for CHB disease management.


Visual selection and maintenance of the cell lines with high plant regeneration ability and low ploidy level in Dianthus acicularis by monitoring with flow cytometry analysis.
Efficient plant regeneration system from cell suspension cultures was established in D. acicularis (2n=90) by monitoring ploidy level and visual selection of the cultures. The ploidy level of the cell cultures closely related to the shoot regeneration ability. The cell lines comprising original ploidy levels (2C+4C cells corresponding to DNA contents of G1 and G2 cells of diploid plant, respectively) showed high regeneration ability, whereas those containing the cells with 8C or higher DNA C-values showed low or no regeneration ability. The highly regenerable cell lines thus selected consisted of compact cell clumps with yellowish color and relatively moderate growth, suggesting that it is possible to select visually the highly regenerable cell lines with the original ploidy level. All the regenerated plantlets from the highly regenerable cell cultures exhibited normal phenotypes and no variations in ploidy level were observed by flow cytometry (FCM) analysis.


Cellular interaction and antibacterial efficacy of two hydraulic calcium silicate-based cements: Cell-dependent model.
This study investigated cytotoxic probability, osteogenic potential, and antibacterial efficacy of two pulp-capping hydraulic calcium-silicate cements. For osteogenic potential and cytotoxicity evaluation, mesenchymal stem cells (MSCs) and materials disc-shaped specimens were used. Increase or decrease in a number of proliferating MSCs was calculated after three intervals. Alkaline phosphatase (ALP) levels in osteogenic media were normalized to the total protein content of cells and measured spectrophotometrically. Antibacterial efficiency through growth curves of Streptococcus mutans in direct contact with tested materials. Biodentine showed the highest number of proliferating MSCs (278000.41 ± 4000.06, after 72 h) and the highest concentration of ALP after 12 days (209.26 ± 7.17 μU/μg protein). It showed the lowest slope (0.003 ± 0.0005) of S. mutans strains growth curves after 18 h. Biodentine proved a highly significant osteogenic ability and gave a significant reduction of S. mutans growth.


Prolonged morning stiffness is common in hand OA and does not preclude a diagnosis of hand osteoarthritis.
Prolonged morning stiffness (>60 min) is considered a symptom of inflammatory arthritis, but has a poor discriminative ability. Knowledge about morning stiffness in patients with hand osteoarthritis (OA) is lacking. We therefore studied morning stiffness in patients with hand OA. Patients with primary hand OA according to their treating rheumatologist in the Hand OSTeoArthritis in Secondary care (HOSTAS) cohort were studied. Severity of morning stiffness was examined with Australian/Canadian hand OA index (AUSCAN) and presence and duration of morning stiffness were examined with a standardized questionnaire. Association of patient and disease characteristics with prolonged morning stiffness (>60 min) were analyzed with logistic regression. In total 519 of 538 patients had available data about duration of morning stiffness, of whom 89 (17%) had prolonged morning stiffness. Severity of stiffness was mild in 158 of 525 (30%), intermediate in 194 (37%), severe in 97 (18%) and extreme in 19 (4%) patients. Patients with prolonged morning stiffness reported more pain, worse physical function and had a reduced mental and physical quality of life. Patients with prolonged morning stiffness also had more severe radiographic disease, although the association did not reach statistical significance. Prolonged and severe morning stiffness are frequently present in patients with hand OA. Patients with these symptoms report more pain in general and have a lower quality of life than patients that do not report these symptoms. Prolonged morning stiffness does not preclude a diagnosis of hand OA.


Pulmonary hypertension- a novel phenotypic hypothesis of Kabuki syndrome: a case report and literature review.
Pediatric pulmonary hypertension (PH) is a serious and rare disease that is often derived from genetic mutations. Kabuki syndrome (KS) is a chromosomal abnormality disease that has its origin in the mutation of lysine methyltransferase 2D(KMT2D). Recent evidence has shown that KMT2D mutations are associated with pediatric pulmonary disorders. However, the relationship between the clinical courses of PH and the KMT2D mutation is reported in extremely few cases. Therefore, in this paper, a case was presented and previous literature was reviewed for better understanding of the correlation between pediatric PH and KMT2D mutations. A 3-year-old girl was transferred to our center for severe cough, shortness of breath, fatigue and fever. Physical examination revealed facial deformities and growth retardation. Echocardiography showed a small atrial septal defect (ASD), and right heart catheterization indicated a significant increase in pulmonary vascular pressure and resistance. The genetic test suggested that she had a KMT2D gene mutation. The patient was finally diagnosed with KS. She was given targeted drugs to reduce pulmonary vascular pressure, but the effect was unsatisfactory. KS can be complicated with multiple organ malformations and dysfunction. With the progress of next generation sequencing, an increasing number of new phenotypes related to KMT2D mutations have been reported. A bold hypothesis is proposed in this article, that is, PH may be a new phenotype associated with KMT2D mutations. It is suggested that KS and PH should be differentiated from each other to avoid delayed diagnosis and treatment in clinical practice. There is no specific drug for KS treatment. The prognosis of children with inherited PH is usually poor, and lung transplantation may increase their survival rates.