Sorption of lead from aqueous solution by chemically modified carbon adsorbents.
An indigenously prepared, steam activated and chemically modified carbon from husk and pods of Moringa oleifera (M. oleifera), an agricultural waste, was comparatively examined as an adsorbent for the removal of lead from aqueous solutions. Studies were conducted as a function of contact time, initial metal concentration, dose of adsorbent, agitation speed, particle size and pH. Maximum uptake capacities were found to be, 98.89, 96.58, 91.8, 88.63, 79.43% for cetyltrimethyl ammonium bromide (CTAB), phosphoric, sulfuric, hydrochloric acid treated and untreated carbon adsorbents, respectively. Bangham, pseudo-first- and second-order, intra-particle diffusion equations were implemented to express the sorption mechanism by utilized adsorbents. Adsorption rate of lead ions was found to be considerably faster for chemically modified adsorbents than unmodified. The results of adsorption were fitted to both the Langmuir and Freundlich models. Satisfactory agreement between the metal uptake capacities by the adsorbents at different time intervals was expressed by the correlation coefficient (R(2)). The Langmuir model represented the sorption process better than the Freundlich one, with R(2) values ranging from 0.994 to 0.998.


Uncommon histopathological findings in fatal measles infection: pancreatitis, sialoadenitis and thyroiditis.
We report uncommon histopathological findings in fatal measles infection. We describe the autopsies of four patients who died during a measles outbreak in São Paulo, Brazil, in 1997. Two of the patients were children receiving chemotherapy for non-Hodgkin's lymphoma, one was an adult with acquired immunodeficiency syndrome (AIDS) and the fourth was an apparently healthy woman. All patients had their deaths attributed to measles pneumonia. The autopsies revealed extensive giant cell pneumonia and diffuse alveolar damage, severe acute pancreatitis, necrotizing sialoadenitis and thyroiditis due to measles. Measles antigen was detected in lung tissue using a monoclonal anti-measles antibody. : Pancreatitis, thyroiditis and sialoadenitis are not previously reported histopathological findings in measles infection. Pancreatitis is a potentially severe complication and should be considered when treating patients with atypical measles.


Complexes of low energy beta emitters 47Sc and 177Lu with zoledronic acid for bone pain therapy.
Targeted radiopharmaceuticals have been mostly developed to visualize and/or treat oncologic diseases. In targeted radiotherapy radionuclide selection is a key issue, because the radionuclide should provide the appropriate radiation absorbed dose, matching the desirable biologic effect, but at the same time it should preclude irradiation of surrounding healthy tissues. Among the last generation of bisphosphonates with cyclic side chains, zoledronic acid is the most potent bisphosphonate, described till now, which inhibits bone resorption. In this paper, we describe the synthesis, properties and hydroxyapatite binding of zoledronic acid labeled with two low energy beta emitters, (47)Sc and (177)Lu. Radiochemicals labeled with low energy electron emitters are preferred, because they deliver both a therapeutic dose to the bone and spare the bone marrow. Hydroxyapatite adsorption experiments have shown that the binding values obtained with complexes of zoledronic acid labeled with (46)Sc and (177)Lu are much higher than those of bisphosphonates labeled with (153)Sm and (166)Ho. Hence, complexes of zoledronic acid with either (46)Sc or (177)Lu seems to be a promising radiopharmaceutical for bone pain therapy.


Synthesis of calcineurin-resistant derivatives of FK506 and selection of compensatory receptors.
We used olefin metathesis to synthesize C40 derivatives of FK506 and measured their ability, when complexed to FKBP12, to inhibit calcineurin's phosphatase activity. We identified modular dimerization domains (CABs) containing segments of the calcineurin A and B polypeptides. These CABs respond to FK506 both when overexpressed in mammalian cells and in yeast or mammalian three-hybrid assays. Using chemical genetic selection, we identified compensatory mutant CABs that respond to a calcineurin-resistant FK506 derivative at concentrations well below the response threshold for CABs containing only wild-type calcineurin sequence. These reagents provide a small molecule-protein combination orthogonal to existing dimerizer systems and may be used with existing systems to increase the complexity of induced-proximity experiments. This new use of the "bump-hole" strategy protects target cells from complications arising from the inhibition of endogenous calcineurin.


Load-induced increase in muscle activity during 30° abduction in patients with rotator cuff tears and control subjects.
Rotator cuff muscles stabilise the glenohumeral joint and contribute to the initial abduction phase with other shoulder muscles. This study aimed to determine if the load-induced increase in shoulder muscle activity during a 30° abduction test is influenced by asymptomatic or symptomatic rotator cuff pathologies. Twenty-five patients with unilateral rotator cuff tears (age, 64.3 ± 10.2 years), 25 older control subjects (55.4 ± 8.2 years) and 25 younger control subjects (26.1 ± 2.3 years) participated in this study. Participants performed a bilateral 30° arm abduction and adduction movement in the scapular plane with handheld weights (0-4 kg). Activity of the deltoid, infraspinatus, biceps brachii, pectoralis major, latissimus dorsi and upper trapezius muscles was analysed at maximum abduction angle after normalisation to maximum voluntary contraction. Shoulders were classified into rotator cuff tendinopathy, asymptomatic and symptomatic rotator cuff tears, and healthy based on magnetic resonance images. A linear mixed model (loads, shoulder types) with random effects (shoulder identification) was applied to the log-transformed muscle activities. Muscle activity increased with increasing load in all muscles and shoulder types (P < 0.001), and 1-kg increments in additional weights were significant (P < 0.001). Significant effects of rotator cuff pathologies were found for all muscles analysed (P < 0.05). In all muscles, activity was at least 20% higher in symptomatic rotator cuff tears than in healthy shoulders (P < 0.001). Symptomatic rotator cuff tears showed 20-32% higher posterior deltoid (P < 0.05) and 19-25% higher pectoralis major (P < 0.01) activity when compared with asymptomatic tears. Rotator cuff pathologies are associated with greater relative activity of shoulder muscles, even with low levels of additional load. Therefore, the inclusion of loaded shoulder tests in the diagnosis and rehabilitation of rotator cuff pathologies can provide important insight into the functional status of shoulders and can be used to guide treatment decisions. Level 2. Ethical approval was obtained from the regional ethics committee (Ethics Committee Northwest Switzerland EKNZ 2021-00182), and the study was registered at clinicaltrials.gov on 29 March 2021 (trial registration number NCT04819724, https://clinicaltrials.gov/ct2/show/NCT04819724 ).


The larva of Drusus vinconi Sipahiler, 1992 (Trichoptera, Limnephilidae, Drusinae).
This paper describes the previously unknown larva of Drusus vinconi Sipahiler, 1992. Information on the morphology of the 5th larval instar is given, and the most important diagnostic features are illustrated. In the context of existing identification keys the larva of Drusus vinconi keys together with Drusus annulatus (Stephens, 1837), Drusus biguttatus (Pictet, 1834), Drusus ingridae Sipahiler, 1993, Hadimina torosensis Sipahiler, 2002 and Leptodrusus budtzi (Ulmer, 1913). These species differ in the contours of the pronotum in lateral view, the presence/absence of the pronotal transverse groove, the shape of the median notch of the pronotum (in anterior view), pronotal sculpturing, presence/absence of the lateral carina of the head capsule, the number of proximo-dorsal setae on the mid-and hind femora, where the lateral fringe starts on the abdomen, and in geographic distribution. With respect to zoogeography, Drusus vinconi is a (micro-)endemic of the Western Pyrenees. The species prefers stony substratum in springs and springbrooks of the montane and subalpine region (Graf et al. 2008; Sipahiler 1992, 1993). As a grazer, the larvae of Drusus vinconi feed on biofilm and epilithic algae.


Purification and characterization of a low molecular weight cysteine proteinase inhibitor from bovine muscle.
A low-Mr tight binding proteinase inhibitor was purified from bovine muscle by alkaline denaturation of cysteine proteinases, gel filtration on Sephadex G-75 and affinity chromatography on carboxymethyl-papain-Sepharose. Chromatofocusing separated three isoforms which are similar in their Mr of about 14 000, their stability with heating at 80 degrees C and their inhibitory activity towards cathepsin H, cathepsin B and papain. The equilibrium constants (Ki) were determined for these three cysteine proteinases but for cathepsin H, association (kass) and dissociation (kdiss) rate constants were also evaluated. Ki values of 56 nM and 8.4 nM were found for cathepsin B and cathepsin H, respectively. For papain, Ki was in the range of 0.1-1 nM. The kinetic features of enzyme-inhibitor binding suggest a possible role for this low-Mr protein inhibitor in controlling 'in vivo' cathepsin H proteolytic activity. With regard to cathepsin B, such a physiological role was less evident.


Participation of the g = 1.9 and g = 1.82 EPR forms of the semiquinone-iron complex, QA-.Fe2+ of photosystem II in the generation of the Q and C thermoluminescence bands, respectively.
Following illumination at 200 K, the charge recombination reactions and the origin of the thermoluminescence (TL) bands appearing at about 0 degree C (Q band) and +50 degrees C (C band) in the glow curve were investigated by comparative TL and EPR measurements in DCMU-treated photosystem II particles. Decay half-time measurements carried out at -25 degrees C and +25 degrees C, respectively, suggest that the S2 state (multi-line signal) undergoes charge recombination with the g = 1.9 form of the semiquinone-iron complex, QA-.Fe2+, resulting in the appearance of the Q band, and that the g = 1.82 form of QA-.Fe2+ back-reacts with the oxidized tyrosine, YD+ (Signal IIs), accounting for the generation of the C band.


Accelerated atherogenesis occurs following platelet destruction and increases in megakaryocyte size and DNA content.
Platelets and megakaryocytes have a role in atherogenesis. In this study the effect of platelet destruction, caused by injection of serum containing anti-platelet antibodies, on the development of atheroma and on megakaryocyte size and DNA content was studied in rabbits on a high cholesterol diet. Seven days after destruction of the circulating platelets a significant (150% and 300% in two separate studies) increase in the area of atheroma in the aorta was demonstrated. Histological examination revealed that large quantities of extracellular lipid and connective tissue were present in these plaques. The acceleration of atherogenesis in this model was found to be preceded by a significant increase in megakaryocyte size and in the frequency of megakaryocytes with a high DNA content. Platelets derived from large, high ploidy megakaryocytes may be of importance for the development of the atherosclerotic lesion. Neither the endothelial permeability as assessed by injection of Evans blue nor the prostacyclin production by the aorta of animals injected with anti-platelet serum were significantly different from the aortas of control animals.


Arsenic, tobacco use, and lung cancer: An occupational cohort with 27 follow-up years.
We explored the shape of the exposure-response relationship of arsenic-related lung cancer and the interaction between arsenic and tobacco use. A total of 3278 tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. After excluding radon-exposed miners and former smokers, 1620 miners were included into the sub-cohort. Lung cancer risks were estimated by modeling total exposure and intensity of arsenic exposure. The cohort experienced 73,866 person-years and 414 lung cancer cases. Firstly, the ERR/mg/m3-year was 0.0033 (95% CI: 0.0014-0.0045) in arsenic concentration <3 mg/m3 and 0.0056 (95% CI: 0.0035-0.0073) in arsenic concentration ≥3 mg/m3. After adjusting for cumulative arsenic exposure, and the ERR/mg/m3 increased with increasing intensity (0.129 (95% CI: 0.039, 0.189)). Secondly, an unique aspect of this population was the early age at first arsenic exposure for workers. Results showed that lung cancer incidence risk from exposed in childhood (<13 years) was non-significantly greater than those in other age groups (13-17 and ≥ 18 years). Finally, the most likely joint effects of inhaled arsenic and tobacco use was sub-multiplicative. This study enlightened us that for fixed cumulative arsenic exposure, higher concentration over shorter duration might be more deleterious than lower concentration over longer duration. Substantial reductions in the lung cancer burden of smokers exposed to arsenic could be achieved by reductions in either exposure.


Therapeutic progress--review XXXI. Therapeutic progress in intensive care sedation and analgesia. Part II--Drug selection.
In part I of this review the principles governing the uses of analgesics and sedatives in the ITU were considered. In part II we shall review the drugs available considering first, symptomatic therapy and secondly, regional analgesia.


Cognitive antecedents of coronary heart disease.
The purpose was to explore cognitive antecedents of CHD proneness in an attempt to avoid some of the problems besetting research focused on type A. The theoretical framework was the cognitive orientation theory by Kreitler and Kreitler which shows how cognitive contents, primarily beliefs about goals, norms, the self and reality guide human behavior and enable its prediction and change. The hypotheses referred to endorsement of beliefs orienting towards CHD-involved behaviors, inconsistencies among belief types and the relation of the beliefs to risk factors in CHD patients as compared to the controls. A self-administered questionnaire was constructed assessing endorsement of four belief types. Subjects were 92 males under 60: 44 with CHD, and two control groups: 28 orthopedic patients without CHD, and 20 healthy subjects. Results showed that CHD individuals scored higher than the controls on the overall beliefs measure, beliefs about norms and about self, had higher inconsistency scores, and had more correlations between belief measures and risk factors (e.g. blood pressure, cholesterol). Discussion centered on suggesting a definition of CHD-proneness as consisting of a sustained externally-maintained tension-producing cognitive-motivational conflict, and on the psychometric and practical implications of the findings.


A 57-Year-Old Woman With Progressive Left Hand Clumsiness and Falls.
A 57-year old woman presented with left hand pain, periodic leg movement during sleep, gradual onset of stiffness, clumsiness, and falls. Neurological examination showed: generalized rigidity and bradykinesia. There was left hand dystonic posturing and ideomotor apraxia, as well as mirror movements of upper limbs and stimulus-sensitive myoclonus. The patient had a high-pitched voice and hypophonia (Video S1). Experts discuss localization and the syndromic diagnosis and predict the underlying pathology. The pathological diagnosis is then provided and clinical learning points are considered.


In vivo effects of lipopolysaccharide on lymphoid and non-lymphoid cells in the mouse spleen. Suppressive and adjuvant effects of LPS on the development of specific antibody forming cells in situ.
Mice were immunized i.v. with 2,4,6-trinitrophenyl (TNP)-carrier conjugates and received lipopolysaccharide (LPS) before, simultaneously with or after these antigens, in order to study the effects of LPS on the in situ development of anti-TNP antibody forming cells in the spleen. LPS given before, simultaneously with or shortly after the thymus dependent (TD) antigen TNP-keyhole limpet haemocyanin (KLH) suppressed the development of anti-TNP antibody forming cells in the spleen, but serum IgM-anti-TNP titres were not reduced, suggesting a selective inhibiting effect of LPS on the local immune response in the spleen. Splenic responses to thymus independent (TI) antigens TNP-Ficoll and TNP-LPS were not reduced when these antigens were administered one day after LPS. LPS given 4 days after TNP-KLH and 1 day before killing of the animals had induced severe alterations in splenic histology, but we found no marked influence on numbers and distribution pattern of anti-TNP forming cells. Results indicate that the LPS induced suppression of the immune response to TD antigens in the spleen is not caused by a direct effect of LPS on antigen reactive B-lymphocytes or on the anti-TNP antibody forming cells themselves. Possible explanations for the LPS-induced immunosuppression are discussed.


Epigenetics: a key regulator of platyhelminth developmental biology?
The Platyhelminthes (flukes/flatworms) are a large group of derived metazoans beautifully adapted for existence in diversely challenging ecosystems. As tractable examples of development and self-regeneration or as causative agents of aquacultural, veterinary and biomedically-relevant parasitic diseases, the platyhelminths are subject to intensive inter-disciplinary research. Given the complex lifestyles exhibited by individuals within this phylum, we postulate that epigenetic processes feature in many aspects of platyhelminth lifecycle diversity, development and environmentally-driven adaptations.


The Impact of Chemical Probes in Drug Discovery: A Pharmaceutical Industry Perspective.
Chemical probes represent an important component of both academic and pharmaceutical drug discovery research. As a complement to prior reviews that have defined this scientific field, we aim to provide an industry perspective on the value of having high-quality chemical probes throughout the course of preclinical research. By studying examples from the internal Merck pipeline, we recognize that these probes require significant collaborative investment to realize their potential impact in clarifying the tractability and translation of a given therapeutic target. This perspective concludes with recommendations for chemical probe discovery aimed toward maximizing their potential to identify targets that result in the successful delivery of novel therapeutics.


Immunocytochemical study of angiotensin II cell bodies in the rat thalamus.
The distribution of angiotensin II cell bodies in the thalamus of the rat was studied by means of intratissue injections of colchicine and using an indirect immunoperoxidase technique. The densest clusters of immunoreactive perikarya were observed in the nuclei geniculatum laterale, medialis dorsalis, ventralis posterior, centralis lateralis, centralis medialis and anterior dorsalis, whereas the nuclei lateralis posterior, lateralis and geniculatum laterale dorsalis had the lowest density. In other thalamic nuclei, geniculatum mediale, lateralis anterior, paraventricularis and ventralis medialis, the density of angiotensin II cell bodies was intermediate. In all these thalamic nuclei, small, round immunoreactive cells with short processes were observed.


Neurodegenerative Disorders and Sleep.
Patients suffering from neurodegenerative conditions frequently report sleep complaints, such as insomnia and excessive daytime sleepiness. These symptoms are likely multifactorial, caused by their underlying neurologic disorder and also by medications and other comorbidities associated with the progressive condition. A detailed history, sleep logs, actigraphy, or polysomnography may be necessary to properly diagnosis and manage these patients. Improvement in sleep may result in improvement in neurologic symptoms and quality of life in this population. There is growing evidence that disrupted sleep may lead to acceleration in the progression of the neurodegenerative disorder and may play a role in the pathogenesis.


Practical Cross-Coupling between O-Based Electrophiles and Aryl Bromides via Ni Catalysis.
Cross-coupling of various O-based electrophiles with aryl bromides was developed through Ni-catalyzed C-O activation in the presence of magnesium. Beside carboxylates, carbamates, and ethers, phenols exhibited excellent reactivity under modified conditions. This chemistry was featured as a simple and environmentally benign process with low catalyst loading and easy manipulations. The method exhibited broad substrate scopes.


Cobalt-catalyzed nucleophilic addition of the allylic C(sp3)-H bond of simple alkenes to ketones.
We herein describe a cobalt/Xantphos-catalyzed regioselective addition of simple alkenes to acetophenone derivatives, affording branched homoallylic alcohols in high yields with perfect branch selectivities. The intermediate of the reaction would be a nucleophilic allylcobalt(I) species generated via cleavage of the low reactive allylic C(sp3)-H bond of simple terminal alkenes.


Comparative evaluation of risk factors, outcome and biomarker levels in young and old acute ischemic stroke patients.
Stroke is the third leading cause of death and disability worldwide accounting for 400-800 strokes per 100,000 individuals each year. In the present study, we compared risk factors, clinical outcome, and prognostic biomarkers NSE, S-100 ßß and ITIH4 levels in young and old acute ischemic stroke (AIS) patients. We compared the risk factors and clinical outcomes in young (n = 38) and old (n = 66) AIS patients admitted to tertiary health care centre in Central India. In addition, we also evaluated NSE, S100ββ & ITIH4 levels in admission and discharge samples of young and old AIS patients with different clinical outcome. Hypertension was a major risk factor in 45% of young and 80% of old AIS patients. Hospital outcome was less favorable in young AIS patients with higher dependent rates of 24% as compared to 12% in old AIS patients. Whereas long term outcome at 12 and 18 months after discharge was more favorable in young AIS patients with low dependency rates of 16% and 11% as compared to 41% and 24% in older AIS patients respectively. Similarly, serum NSE, S100ββ and ITIH4 levels showed a distinct pattern of expression at discharge time in AIS patients with improved and dependent outcome in both the age groups. Young males with hypertension and smoking habits are at a high risk of AIS while old AIS patients are at a greater risk of worse long term outcome. Serum levels of NSE and S100ββ are independent predictors of outcome in AIS patients. Similarly, it also suggests that serum ITIH4 levels could be used as a potential biomarker for predicting the outcome in AIS patients.


Controlled trial of a short and a prolonged course with ciprofloxacin in patients undergoing transurethral prostatic surgery.
The efficacy of a short (Group I) and a prolonged (Group II) course with ciprofloxacin was assessed in patients undergoing transurethral prostatic resection for benign hyperplasia or cancer of the prostate and compared with that of controls without antibiotic (Group III). Both regiments significantly reduced the frequency of postoperative bacteriuria (p less than 0.01) and of severe infectious complications (p = 0.004) as compared to the controls. Both regimens were equally effective in preventing perioperative and postoperative acquisition of bacteriuria in patients without bacteriuria at surgery. In patients with bacteriuria before surgery, bacteriuria was found postoperatively in 35% in Group I and 10% in Group II (p = 0.012), but in 82% of the patients in Group III. Ciprofloxacin inhibited all but 7 of 176 bacterial strains at an MIC of less than or equal to 1 microgram/ml. Given orally ciprofloxacin is a valuable alternative antimicrobial for use in conjunction with transurethral prostatic resection. A short course is sufficient for prophylaxis, and adequate therapy is achieved with a prolonged regimen.


Extracts from Seseli mairei Wolff attenuate imiquimod-induced psoriasis-like inflammation by inhibiting Th17 cells.
Seseli mairei Wolff extracts (SMWE) are widely used to treat psoriasis as a Chinese medicine, but their effect and mechanism are unclear. This study verified the effect of SMWE on psoriasis by regulating Th17 cells. HaCaT cells were treated with IL-17A in vitro to evaluate the effect of SMWE on psoriasis. In vivo, the mice psoriasis model was established using imiquimod (IMQ, 62.5 mg/d), and intragastrically treated with the different drugs for six days. The severity of skin inflammation was evaluated with Psoriasis Area and Severity Index (PASI) scores and pathology. The levels of inflammation cytokines were assessed with immunofluorescence, immunochemistry, ELISA, and real-time PCR. The number of Th17 cells was determined with flows. SMWE inhibited the proliferation of HaCaT cells and reduced the IL-17A-induced IL-6 production in vitro. In vivo, SMWE deduced the levels of IL-1β, IL-6, IL-8, IL-17A, IL-17F, IL-22, IL-23, and TNF-α, while increasing the level of IL-10 compared to the model group. SMWE also inhibited the levels of NF-κB, JAK2, and STAT3 proteins, while declining the expressions of Gr-1, and MPO. Interestingly, SMWE significantly decreased the number of Th17 cells. SMWE inhibited the proliferation of HaCaT cells and attenuated the development of psoriasis lesions by inhibiting Th17 cells to regulate the levels of inflammation cytokines.


A Spectroscopic Study of Tautomeric Equilibrium of Salicylideneaniline in ZSM-5 Zeolites.
Salicylideneaniline (SA) sorbed in cation-exchanged M-ZSM-5 (M = H⁺, Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺ and Zn2+) zeolites was studied by spectroscopic techniques assisted by quantum-chemical calculations. The nature of extra-framework cations present in the zeolite void was found to affect the spectral signature of the sorbed SA molecule that points to the shift of tautomeric equilibrium between the enol and keto forms. Small size cations, such as H⁺ and Li⁺, stabilize a cis-keto SA tautomer along with a enol one in the zeolite structure. The calculations indicate that the sorbed cis-keto tautomer may have the dipole large enough to be considered as a zwitterion. New features appearing in the spectra with the increase of the cation size were attributed to the presence of trans-keto SA tautomer, which up to now has been observed only in time-resolved spectroscopic experiments. A strong interaction of the molecule with cations in Zn-ZSM-5 zeolite results in the chelation of enol SA with the divalent Zn2+ ions. The results of the study suggest that the tautomeric equilibrium of molecules belonging to the Schiff base family can be tuned by the confinement in the nanoporous materials via a choice of topology of zeolite framework and the nature of extra-framework cations.


Characterisation of the protein corona using tunable resistive pulse sensing: determining the change and distribution of a particle's surface charge.
The zeta potential of the protein corona around carboxyl particles has been measured using tunable resistive pulse sensing (TRPS). A simple and rapid assay for characterising zeta potentials within buffer, serum and plasma is presented monitoring the change, magnitude and distribution of proteins on the particle surface. First, we measure the change in zeta potential of carboxyl-functionalised nanoparticles in solutions that contain biologically relevant concentrations of individual proteins, typically constituted in plasma and serum, and observe a significant difference in distributions and zeta values between room temperature and 37 °C assays. The effect is protein dependent, and the largest difference between the two temperatures is recorded for the γ-globulin protein where the mean zeta potential changes from -16.7 to -9.0 mV for 25 and 37 °C, respectively. This method is further applied to monitor particles placed into serum and/or plasma. A temperature-dependent change is again observed with serum showing a 4.9 mV difference in zeta potential between samples incubated at 25 and 37 °C; this shift was larger than that observed for samples in plasma (0.4 mV). Finally, we monitor the kinetics of the corona reorientation for particles initially placed into serum and then adding 5 % (V/V) plasma. The technology presented offers an interesting insight into protein corona structure and kinetics of formation measured in biologically relevant solutions, i.e. high protein, high salt levels, and its particle-by-particle analysis gives a measure of the distribution of particle zeta potential that may offer a better understanding of the behaviour of nanoparticles in solution. Graphical Abstract The relative velocity of a nanoparticle as it traverses a nanopore can be used to determine its zeta potential. Monitoring the changes in translocation speeds can therefore be used to follow changes to the surface chemistry/composition of 210 nm particles that were placed into protein rich solutions, serum and plasma. The particle-by-particle measurements allow the zeta potential and distribution of the particles to be characterised, illustrating the effects of protein concentration and temperature on the protein corona. When placed into a solution containing a mixture of proteins, the affinity of the protein to the particle's surface determines the corona structure, and is not dependent on the protein concentration.


The long-term survival in patients with chronic thromboembolic pulmonary hypertension: experience from a single center in China.
The long-term prognosis of patients with chronic thromboembolic pulmonary hypertension (CTEPH) receiving different treatments is deserved to be analyzed in modern era of CTEPH treatment. From 2013 to 2019, a total of 364 patients diagnosed with CTEPH were retrospectively included, 14 patients were lost during follow-up. Among 350 patients included in the final analysis: 123 underwent pulmonary endarterectomy (PEA), 121 received balloon pulmonary angioplasty (BPA), and 106 treated with targeted drug alone. The median period of follow-up was 51.2 months, the estimated survival at 1-, 3-, 5- and 7-year was 97.1%, 93.3%, 86.9%, and 82.0% for the whole cohort; 100%, 99.20%, 96.5% and 92.5% in PEA group; 98.4%, 97.4%, 95.3% and 89.3% in BPA group;92.5%, 81.9%, 70.1% and 66.8% in patients who received targeted drug alone. In comparing with targeted treatment along, results of multivariate Cox analysis after adjusting the confounders showed that receiving PEA decreased the risk of death by 83% (HR [hazard ratio] 0.17, 95% CI [Confidence interval] 0.07-0.44) and receiving BPA decreased the risk of death by 89% (HR 0.11, 95% CI 0.04-0.29). In conclusion, the estimated survival of CTEPH patients at 1-, 3-, 5- and 7-year was 97.1%, 93.3%, 86.9%, and 82.0% respectively. The intervention of revascularization, including PEA and BPA, were preferred than treating with targeted drug alone in the view of long-term prognosis of CTEPH.


Phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts.
The anti-resorptive effects of estrogen on bone metabolism are thought to be mediated through modulation of paracrine factors produced by osteoblastic lineage cells that act on osteoclastic lineage cells. Receptor activator of nuclear factor-kappaB ligand (RANKL) is the essential factor for osteoclast formation and activation and enhances bone resorption. By contrast, osteoprotegerin (OPG), which is produced by osteoblastic lineage cells acts as a decoy receptor that neutralizes RANKL and prevents bone loss. Recently, 17 beta-estradiol was found to stimulate OPG mRNA levels and protein secretion in a human osteoblastic cell line through activation of the estrogen receptor (ER)-alpha. In this study, we assessed the effects of the phytoestrogen genistein on OPG mRNA steady state levels (by semiquantitative RT-PCR and Northern analysis) and protein production (by ELISA) in primary human trabecular osteoblasts (hOB) obtained from healthy donors. Genistein increased OPG mRNA levels and protein secretion by hOB cells by up to two- to six-fold in a dose- (P<0.0001) and time-dependent (P<0.0001) fashion with a maximum effect at 10(-7) M. Co-treatment with the pure ER antagonist ICI 182,780 completely abrogated the stimulatory effects of genistein on OPG protein secretion, indicating that these effects were specific and directly mediated through the ER. Pre-treatment with genistein partially prevented the inhibitory effects of the glucocorticoid dexamethasone on OPG mRNA and protein production. The stimulation of OPG mRNA levels by genistein was not affected by the protein synthesis inhibitor, cycloheximide and was shown to be due to enhancement of OPG gene transcription. In conclusion, our data suggest that the phytoestrogen genistein is capable of upregulating the production of OPG by human osteoblasts. Thus, dietary sources of phytoestrogens may help to prevent bone resorption and bone loss by enhanced osteoblastic production of OPG.


Does retroperitoneal lymph node dissection have a curative role for patients with sex cord-stromal testicular tumors?
Sex cord-stromal tumors account for < 5% of all adult testicular tumors, and 10% are malignant. Due to the limited reported experience, there is no agreement on the best management, especially in patients who have tumors with malignant pathologic features or who present with metastatic disease. The authors attempt to evaluate the role of retroperitoneal lymph node dissection (RPLND) in the management of patients with these malignant sex cord-stromal tumors. Reviewing the Indiana University testis cancer registry revealed 17 patients who underwent RPLND for sex cord-stromal tumors. Pathology was reviewed for features suggestive of malignancy. The data examined included clinical and pathologic stage, surgical procedure, additional therapy received, and outcome. Pathology included Leydig tumors in six patients, Sertoli tumors in four patients, sex cord-stromal tumors in five patients, a granulosa cell tumor in one patient, and a poorly differentiated non-germ cell tumor in one patient. Nine patients had histologic features suggestive of malignancy. Clinical stage at surgery was Stage I in nine patients and Stage IIA-IIIA in eight patients. Patients underwent modified or bilateral RPLND. Nine patients had pathologic Stage I tumors, and the remaining eight patients and had pathologic Stage IIB-IIIA tumors. Follow-up ranged from 8 months to 11 years. Of the eight patients with Stage II-III disease, six patients eventually died of metastatic disease despite additional radiotherapy and/or chemotherapy. Sex cord-stromal tumors have a potentially aggressive malignant behavior that is difficult to predict based on clinical and pathologic features. Although the therapeutic role of RPLND in patients with small-volume metastatic retroperitoneal tumors is unclear, RPLND remains an option to be performed immediately after orchiectomy, especially in patients who have tumors with malignant features and/or small-volume metastatic disease.


Purification and properties of cytochrome p-450 (11beta- and 18-hydroxylase) from bovine adrenocortical mitochondria.
We describe an improved procedure for the preparation of a cytochrome P-450 from bovine adrenocortical mitochondria which catalyzes 11beta- and 18-hydroxylation of steroids. The preparation is based upon chromatography on DEAE cellulose which separates the enzyme from the side-chain cleavage P-450, which can also be prepared in highly purified form from the same tissue extracts. The enzyme behaves as a single compound in glycerol density gradients. The enzyme aggregates at protein concentrations greater than 1 mg/ml to a series of forms of various molecular weights. On Sepharose 4B the enzyme shows a molecular weight of 185 000, while on glycerol density gradients a molecular weight of 1 - 10(6) is observed. The subunit molecular weight determined by electrophoresis on polyacrylamide gels with sodium dodecyl sulfate is 47 500 and the protein appears as a single band. The ratio of 11beta-/18-hydroxylase activities does not change significantly during purification and is constant through the protein peak on glycerol density gradients. Since there appears to be only one subunit species, it seems likely that the two hydroxylase activities are catalyzed by one protein.


Characterization of the zinc binding site of bacterial phosphotriesterase.
The bacterial phosphotriesterase has been found to require a divalent cation for enzymatic activity. This enzyme catalyzes the detoxification of organophosphorus insecticides and nerve agents. In an Escherichia coli expression system significantly higher concentrations of active enzyme could be produced when 1.0 mM concentrations of Mn2+, Co2+, Ni2+, and Cd2+ were included in the growth medium. The isolated enzymes contained up to 2 equivalents of these metal ions as determined by atomic absorption spectroscopy. The catalytic activity of the various metal enzyme derivatives was lost upon incubation with EDTA, 1,10-phenanthroline, and 8-hydroxyquinoline-5-sulfonic acid. Protection against inactivation by metal chelation was afforded by the binding of competitive inhibitors, suggesting that at least one metal is at or near the active site. Apoenzyme was prepared by incubation of the phosphotriesterase with beta-mercaptoethanol and EDTA for 2 days. Full recovery of enzymatic activity could be obtained by incubation of the apoenzyme with 2 equivalents of Zn2+, Co2+, Ni2+, Cd2+, or Mn2+. The 113Cd NMR spectrum of enzyme containing 2 equivalents of 113Cd2+ showed two resonances at 120 and 215 ppm downfield from Cd(ClO4)2. The NMR data are consistent with nitrogen (histidine) and oxygen ligands to the metal centers.


Possible role of short-term parenteral nutrition with fat emulsions for development of haemophagocytosis with multiple organ failure in a patient with traumatic brain injury Roth B, Grande PO, Nillson-Ehle P and Eliasson I. Intensive Care Med 1993; 19: 111-114.
This paper describes a case-report of a 21-year-old woman who sustained an isolated traumatic brain injury following a road traffic accident. After a 3-day period of parenteral nutrition including fat (Intralipid 20%) she developed hypertriglyceridaemia and 'creaming plasma', with a rash, high fever, hypertension, raised inracranial pressure, hepatic and renal failure, haemolysis, marked thrombocytopenia, and leucopenia, coagulation disorder and pulmonary failure, suggestive of hyperactivation of the monocyte-macrophage system. Treatment involved cessation of the lipid emulsion infusion and steroids. 6 months after the accident, the patient was well recovered with only minor neurological sequelae.


Human topoisomerase I mediates illegitimate recombination leading to DNA insertion into the ribosomal DNA locus in Saccharomyces cerevisiae.
Eukaryotic type I DNA topoisomerases catalyze the relaxation of supercoiled DNA, and play a critical role in DNA replication, transcription and recombination. They are highly conserved, both in sequence and mechanism of activity, from yeast to mammalian cells. We tested the effect of human topoisomerase I (hTOP1) on illegitimate insertion in yeast by expressing the hTOP1 gene in top1Delta yeast ( ytop1Delta) cells. hTOP1 increased the frequency of illegitimate recombination into genomic DNA by 20- to 90-fold relative to the level in ytop1Delta cells, while it had no effect on homologous integration. The addition of the topoisomerase I inhibitor camptothecin blocked this increase in the level of illegitimate insertion. The expression of hTOP1 also significantly enhanced the fraction of integration events in ribosomal DNA (rDNA)-from 16% to 60%, indicating that the rDNA is a highly preferred target for hTOP1. Integrations occurred at the consensus sequence 5' (T/A) (G/C/A) (T/A) (T/C/A) 3' in hTOP1 expressing cells. A similar preferred break-site consensus sequence was previously identified in vitro for topoisomerases from rat liver and wheat germ.


SlWHY2 interacts with SlRECA2 to maintain mitochondrial function under drought stress in tomato.
Drought stress in plants leads to inhibition of photosynthesis and respiration, accumulation of reactive oxygen species (ROS), and reprogramming of gene expression. Here, we established that the tomato (Solanum lycopersicum) WHIRLY2 (SlWHY2) gene, which encodes a mitochondrial single-stranded DNA-binding protein, was significantly induced by drought stress. Under drought conditions, SlWHY2 RNAi plants showed more wilting and lower fresh weight, chlorophyll content, quantum yield of photosystem I (PSI; YI), and maximal photochemical efficiency of PSII (Fv/Fm) than the wild type (WT). Drought treatment also caused the SlWHY2 RNAi lines to accumulate more ROS than the WT, and the silenced lines had lower AOX (alternative oxidase) activity. As expected, the mitochondrial membrane potential (MMP) was less stable in the SlWHY2 RNAi lines. The expression levels of seven genes in the mitochondrial genome (SYCF15, NAD7, NAD4, COS2, COX1, COX2, and COX3) were decreased even more in the SlWHY2 RNAi lines than they were in the WT under drought stress. SlWHY2 interacted directly in vivo and in vitro with SlRECA2, a mitochondrial recombinase A that is important for mitochondrial DNA recombination and repair. These results suggest that SlWHY2 plays an essential role in maintaining mitochondrial function and enhancing drought tolerance in tomato.


The in vitro lymphocyte/endothelium binding assay. An improved method employing light microscopy.
The in vitro lymphocyte binding assay (HEV assay) has proved to be a useful approach for examining the first step of lymphocyte migration, i.e., homing to organs containing high endothelial venules (HEVs). Since fluorescence-labelled standard lymphocytes are usually included in each assay to account for day-to-day variations, HEV preparations have to be evaluated by fluorescence microscopy. Thus no counterstaining can be performed and HEVs without adherent lymphocytes cannot easily be recognized. Because the preparations are not suitable for storage they must be evaluated within a short time. In this study an improved technique is described which permits HEV preparations made with fluorescence-labelled standard lymphocytes to be evaluated by light microscopy in counterstained sections. The phenotypes of the sample lymphocytes can be determined by staining for surface antigens on the same slides and the preparations obtained are permanent.


Generation of antigen specific cytotoxic T lymphocytes (CTL) directed against class II molecules expressed by activated T cells.
Mitogen-activated T cells were used to provide a source of Class II antigens to CTL originally stimulated against mononuclear cells expressing both foreign Class I and Class II determinants. Our results indicated that 7-10-day-old activated T antigen-presenting cells, which shared only Class II antigens with the original priming cell, were able to stimulate the differentiation of CTL-recognizing Class II determinants. The use of 14-day-old activated T cells as target cells in the CML assay, compared with 72 h PHA blasts or 7-day-old activated T cells, enabled a more sensitive detection of the anti-Class II CTL.


Effect of epigenetics on vitamin D levels: a systematic review until December 2020.
The association between epigenetic modification of the genes involved in the vitamin D metabolic pathway and vitamin D metabolites' status has been elucidated incompletely. This study aims to review the studies on the mentioned association and create a brighter view of this topic. A systematic literature search was conducted in Medline database (PubMed), Scopus, and Web of Science up to the end of November 2020. Original articles which reported the effect of epigenetic alteration-methylation level or its changes-of genes involved in vitamin D regulation on the vitamin D metabolites serum level or its changes were included. The National Institutes of Health (NIH) checklist was used to assess the quality of included articles. Among 2566 records, nine reports were included in the systematic review according to the inclusion and exclusion criteria. Studies discussed the contribution of methylation status of members of the cytochrome P450 family (CYP2R1, CYP27B1, CYP24A1), and Vitamin D Receptor (VDR) genes to vitamin D level variance. CYP2R1 methylation status could regulate the contributing factors affecting the vitamin D serum level and predict response to vitamin D supplementation. Studies revealed that impaired methylation of CYP24A1 occurs in response to an increase in serum level of 25-hydroxyvitamin D (25(OH)D). It is reported that the association between methylation levels of CYP2R1, CYP24A1, and VDR genes and 25(OH)D level is not affected by the methyl-donors bioavailability. The epigenetic modification of the vitamin D-related genes could explain the vitamin D levels variation among populations. Large-scale clinical trials in various ethnicities are suggested to find the effect of epigenetics on vitamin D response variation. The systematic review protocol was registered on PROSPERO (registration number: CRD42022306327).


Movement kinematics and proprioception in post-stroke spasticity: assessment using the Kinarm robotic exoskeleton.
Motor impairment after stroke interferes with performance of everyday activities. Upper limb spasticity may further disrupt the movement patterns that enable optimal function; however, the specific features of these altered movement patterns, which differentiate individuals with and without spasticity, have not been fully identified. This study aimed to characterize the kinematic and proprioceptive deficits of individuals with upper limb spasticity after stroke using the Kinarm robotic exoskeleton. Upper limb function was characterized using two tasks: Visually Guided Reaching, in which participants moved the limb from a central target to 1 of 4 or 1 of 8 outer targets when cued (measuring reaching function) and Arm Position Matching, in which participants moved the less-affected arm to mirror match the position of the affected arm (measuring proprioception), which was passively moved to 1 of 4 or 1 of 9 different positions. Comparisons were made between individuals with (n = 35) and without (n = 35) upper limb post-stroke spasticity. Statistically significant differences in affected limb performance between groups were observed in reaching-specific measures characterizing movement time and movement speed, as well as an overall metric for the Visually Guided Reaching task. While both groups demonstrated deficits in proprioception compared to normative values, no differences were observed between groups. Modified Ashworth Scale score was significantly correlated with these same measures. The findings indicate that individuals with spasticity experience greater deficits in temporal features of movement while reaching, but not in proprioception in comparison to individuals with post-stroke motor impairment without spasticity. Temporal features of movement can be potential targets for rehabilitation in individuals with upper limb spasticity after stroke.


Phase-dependent electron transport through a quantum wire on a surface.
Electron transport through a quantum wire in the presence of external periodic energy-level modulations with different on-site phases is studied within the time evolution operator method for a tight-binding Hamiltonian. It is found that in the presence of spatial symmetry of the system and no source-drain and static gate voltages the pumping current can be generated. Moreover, for a wire which is tunnel-coupled to the underlying substrate, the current flowing through an unbiased wire does not fade away but increases with the wire-surface coupling. For randomly chosen phases at every wire site two regimes of the phase-averaged current are found which are related to small and high wire density of states.


An office approach to hematuria and proteinuria.
An organized practical approach for the pediatrician to use in evaluating a child with hematuria or proteinuria emphasizes common conditions and stepwise laboratory/radiologic investigations. Additional points of emphasis include when to refer to a pediatric nephrologist or urologist and when to consider renal biopsy. Real case statistics and salient examples from the major published studies should assist the pediatrician in counseling the patient and his or her family, especially when there is no medical indication to refer to a specialist.


Terrestrial Soundscapes: Status of Ecological Research in Natural and Human-Dominated Landscapes.
Soundscape ecological research in terrestrial systems is relatively new. In this paper, I present a brief summary of the origins of this research area, describe research questions related to several research thrusts that are ongoing, summarize several soundscape projects that exist and how these relate to the research thrusts, and briefly describe the work of a global network of scientists, musicians, and engineers that are attempting to move this new field forward.


Endocrine assessments of fetal-placental well-being.
Continued advances in perinatology and neonatology and the introduction of biochemical and biophysical methods for evaluating pregnancy have substantially improved the perinatal outcome. Biochemical evaluation of placental function appears to play an important role in the management of complications of early and late pregnancy. Improvements in methodology and increased experience in the application of the various techniques have enhanced our ability to diagnose normal and abnormal pregnancy. The various new placental proteins recently described have not yet found their place in modern obstetrics and thus far they do not seem to offer distinct advantage over more established methods for assessing fetoplacental function.


Rebound of multiple sclerosis activity after fingolimod withdrawal due to planning pregnancy: Analysis of predisposing factors.
Rebound of multiple sclerosis (MS) activity has been described after the withdrawal of high-efficacy drugs, but its impact during pregnancy is less known. We describe a series of cases of rebound syndrome after the cessation of fingolimod due to pregnancy planning. The clinical and radiological data of 7 MS patients who discontinued fingolimod therapy between May 2012 and March 2018 to plan a pregnancy was analysed. Three (42.8%) of the 7 patients experienced a rebound effect, all of whom became pregnant. During pregnancy, the 3 patients had a mean (SD) of 5.3 (1.3) relapses, and 13 of the 15 relapses were treated with intravenous steroids and/or immunoglobulin. These patients experienced a median increase of 3 points in the Expanded Disability Status Scale (range, 2-4), as well as a median increase of 27 new gadolinium-enhancing lesions (range, 9-40) and 38 new T2 lesions in a post-partum MRI (range, 21-70). The 3 pregnancies resulted in the delivery of healthy babies. A strong correlation was found between the lymphocyte count at fingolimod onset and the annual relapse rate in the period without therapy (r= -0.84, p = 0.005). The time to first relapse was shorter in patients who had <300/μl lymphocytes at fingolimod onset (median time 46 vs 426 days, p = 0.010). Rebound activity after fingolimod suspension represents a severe long-lasting inflammatory syndrome that may affect up to 40% of female MS patient who discontinue therapy due to pregnancy planning. Lymphopenia (<300/μl) in the first 3 months of fingolimod onset may predispose patients to suffer earlier and higher disease activity upon cessation.


Reduced expression of transcription factor AP-2α is associated with gastric adenocarcinoma prognosis.
This study aims to investigate the expression and prognostic significance of activator protein 2α (AP-2α) in gastric adenocarcinoma. AP-2α expression was analyzed using real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical staining methods on tissue samples from a consecutive series of 481 gastric adenocarcinoma patients who underwent resections between 2003 and 2006. The relationship between AP-2α expression, clinicopathological factors, and patient survival was investigated. RT- qPCR results showed that the expression of AP-2α mRNA was reduced in tumor tissue samples, compared with expression in matched adjacent non-tumor tissue samples (P = 0.009); this finding was confirmed by western blotting analysis (P = 0.012). Immunohistochemical staining data indicated that AP-2α expression was significantly decreased in 196 of 481 (40.7%) gastric adenocarcinoma cases; reduced AP-2α expression was also observed in patients with poorly differentiated tumors (P = 0.001) and total gastric carcinomas (P = 0.002), as well as in patients who underwent palliative tumor resection (P = 0.004). Additionally, reduced expression of AP-2α was more commonly observed in tumors that were staged as T4a/b (P = 0.018), N3 (P = 0.006), and M1 (P = 0.008). Kaplan-Meier survival curves revealed that reduced expression of AP-2α was associated with poor prognosis in gastric adenocarcinoma patients (P<0.001). Multivariate Cox analysis identified AP-2α expression as an independent prognostic factor for overall survival (HR = 1.512, 95% CI = 1.127-2.029, P = 0.006). Our data suggest that AP-2α plays an important role in tumor progression and that reduced AP-2α expression independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.


Axonal Damage in Pediatric Multiple Sclerosis.
Investigators from Georg August University, Gottingen, Germany, analyzed axonal pathology in brain biopsy and autopsy samples from 19 children with early multiple sclerosis (MS).


Association between Endometriosis and Risk of Preeclampsia in Women Who Conceived Spontaneously: A Systematic Review and Meta-analysis.
To evaluate the association between endometriosis and the risk of preeclampsia and other maternal outcomes in spontaneously conceived women. PubMed, MEDLINE, Embase, Scopus, Cochrane Library, Web of Science, and Google Scholar were systemically searched for studies published from inception to November 2021 (CRD42020198741). Observational studies published in English or French that investigated the risk of preeclampsia in women with endometriosis who conceived spontaneously were included. A total of 610 articles were reviewed once duplicates were removed. Inclusion criteria included spontaneous conception and surgical and/or imaging ascertainment of an endometriosis diagnosis. Exclusion criteria included conception using assisted reproductive technologies, multiple pregnancies, chronic hypertension, and unclear diagnoses of endometriosis. Data of selected studies were extracted, and analysis was performed on Review Manager, version 5.4. Quality assessment of included studies for potential risk of bias was evaluated using the Newcastle-Ottawa Scale for cohort studies. Three cohort studies of spontaneous pregnancies were included. Endometriosis was associated with an increased risk of preeclampsia (risk ratio [RR] = 1.47, 95% CI 1.13 -1.89, p = .003; I2 = 0%; n = 3 studies). A sensitivity analysis excluding a study with adenomyosis cases yielded similar risk (RR = 1.44; 95% CI, 1.11-1.87; p = .006; I2 = 0%; n = 2 studies). Having endometriosis did not significantly increase risk of cesarean delivery (RR = 1.38; 95% CI, 0.99-1.92; p = .06; I2 = 80%; n = 2 studies) or postpartum hemorrhage (RR = 1.16; 95% CI, 0.46-2.91; p = .76; I2 = 50%; n = 2 studies). We detected an increased risk of preeclampsia in women with endometriosis who conceived spontaneously. Endometriosis did not seem to increase the risk of cesarean delivery and postpartum hemorrhage, but the number of studies was limited, and the heterogeneity was high.


Large intraparotid facial nerve schwannoma: case report and review of the literature.
Here is reported an extremely rare case of a large intraparotid facial nerve schwannoma in a 32-year-old female who presented with a parotid mass. There had been a long clinical course and sudden onset of facial weakness. Diagnostic evaluation and surgical management are discussed along with a brief review of the literature.


Genetic research and clinical analysis of β-globin gene cluster deletions in the Chinese population of Fujian province: A 14-year single-center experience.
Heterozygotes of HPFH and δβ thalassemia are clinically asymptomatic or have mild hemoglobin (Hb) values. However, when both HPFH and δβ-thalassemia are coinherited with heterozygous β-thalassemia, patients may progress to a clinical phenotype of thalassemia intermedia or thalassemia major. The purpose of this study was to characterize the genotypes and analyze the phenotypes of these disorders in Fujian Province, to offer advice for genetic counseling and accurate prenatal diagnosis in this region. A total of 55 001 subjects were participated in thalassemia screening. 142 subjects with HbF levels ≥10%, before the blood transfusion, were selected for further investigation. Multiplex ligation-dependent probe amplification (MLPA) and Gap-PCR were used to screen for three β-globin gene cluster deletions: Chinese G γ(A γδβ)0 thalassemia and Southeast Asia HPFH (SEA-HPFH) deletion and 1357 bp deletion (NG-000007.3:g.69997-71353 del 1357). A total of 142 patients with HbF (≥10%) were enrolled to characterize the molecular basis of β-globin gene cluster deletions in our study; 22 cases 0.04% (22/55 001) were definitively diagnosed with β-globin gene cluster deletions. Ten cases were heterozygous for the Chinese G γ(A γδβ)0 -thal mutations, 10 cases were heterozygous for SEA-HPFH, and one case was compound heterozygous for SEA-HPFH and the α-thal mutation. The 1357 bp deletion (NG-000007.3:g.69997-71353 del 1357) was detected in one case. Moreover, the hemoglobin A2 levels in patients who were heterozygous for Chinese G γ(A γδβ)0 -thal were statistically lower than in cases with SEA-HPFH deletion(p < 0.05). In Fujian Province, the prevalence of common β-globin gene cluster deletions was 0.04%. What's more, the most common β-globin cluster deletions are the Chinese G γ(A γδβ)0 and SEA-HPFH.


A Review of Current Knowledge on Staphylococcus agnetis in Poultry.
This review aims to summarize recent discoveries and advancements regarding the characteristics of Staphylococcus agnetis (S. agnetis) and its role in poultry pathology. S. agnetis is an emerging pathogen that was primarily associated with mastitis in dairy cattle. After a presumed host jump from cattle to poultry, it was identified as a pathological agent in broiler chickens (Gallus gallus domesticus), causing lameness induced by bacterial chondronecrosis with osteomyelitis (BCO), septicemia, and valvular endocarditis. Economic and welfare losses caused by lameness are global problems in the poultry industry, and S. agnetis has been shown to have a potential to induce high incidences of lameness in broiler chickens. S. agnetis exhibits a distinct repertoire of virulence factors found in many different staphylococci. It is closely related to S. hyicus and S. chromogenes, hence infections caused by S. agnetis may be misdiagnosed or even undiagnosed. As there are very few reports on S. agnetis in poultry, many facts about its pathogenesis, epidemiology, routes of transmission, and the potential impacts on the poultry industry remain unknown.


Simultaneous inhibition of the constitutively activated nuclear factor kappaB and of the interleukin-6 pathways is necessary and sufficient to completely overcome apoptosis resistance of human U266 myeloma cells.
Elevated Nuclear Factor kappaB (NFkappaB) levels have been reported in multiple myeloma cells derived from patients relapsing after chemotherapy. In the search of an in vitro a model with molecular features similar to relapsing lesions, we focused our attention on an IL-6 autocrine human myeloma cell line (U266), characterized by apoptosis resistance due to upregulation of two constitutive signaling pathways: NFkappaB and STAT-3. NFkappaB activity was inhibited with proteasome inhibitory agents, such as PS-341 and Withaferin A, with an IKK inhibitor (Wedelolactone) or with the adenoviral vector HD IkappaBalphamut-IRES-EGFP encoding a mutant IkappaBalpha protein, resistant to proteasomal degradation. We observed that the NFkappaB intracellular dislocation at the beginning of the treatment affected therapeutic effectiveness of PS-341, Withaferin A and Wedelolactone; interestingly, the adenoviral vector was highly effective in inducing apopotosis even with NFkappaB being predominantly nuclear at the time of infection. We also observed that U266 treated with the Interleukin-6 antagonist Sant7 exhibited reduced STAT3 activity and preferential cytoplasmic NFkappaB location; moreover they became capable of undergoing apoptosis mainly from the G1 phase. Adenoviral vector treated U266 have NFkappaB localized completely in the cytoplasm and also showed downregulation of nuclear phospho STAT-3. Finally, combined targeting of NFkappaB and STAT3 signalling pathways was the most effective treatment in inducing apoptosis. These findings suggest that combined NFkappaB and STAT3 targeting warrants further investigations in other apoptosis resistant MM cell lines as well as in suitable MM animal models.


A self-consistent approach to describe unit-cell-parameter and volume variations with pressure and temperature.
A method for the self-consistent description of the large variations of unit-cell parameters of crystals with pressure and temperature is presented. It employs linearized versions of equations of state (EoSs) together with constraints to ensure internal consistency. The use of polynomial functions to describe the variation of the unit-cell angles in monoclinic and triclinic crystals is compared with the method of deriving them from linearized EoSs for d spacings. The methods have been implemented in the CrysFML Fortran subroutine library. The unit-cell parameters and the compressibility and thermal expansion tensors of crystals can be calculated from the linearized EoSs in an internally consistent manner in a new utility in the EosFit7c program, which is available as freeware at http://www.rossangel.net.


Radiofrequency ablation vs microwave ablation for osteoid osteomas: long-term results.
Osteoid osteomas are benign bone tumors commonly treated using thermal ablation. We compare the technical success, complication rates, and long-term efficacy of the two most common ablation types: radiofrequency and microwave. A retrospective study was performed of all osteoid osteoma ablation procedures between 2007 and 2017. A ten-point numerical pain scale was used to quantify symptoms before and after the procedures with > 12-month follow-up. Complications were reported using the Society of Interventional Radiology Adverse Events reporting criteria. Twenty-nine patients successfully underwent 15 radiofrequency ablations and 15 microwave ablations with a technical success rate of 83% for radiofrequency and 100% for microwave (p = 0.23). Long-term recurrence rates (p = 1.0) and complication rates (p = 0.60) were not significantly different for the groups. One patient developed a skin burn following microwave ablation and another developed 12 months of sciatic neuropathy following radiofrequency ablation. Microwave and radiofrequency ablation are safe and effective methods for treating osteoid osteomas with similar long-term efficacies. Although radiofrequency ablation is more commonly reported to result in skin burns, this complication can arise during microwave ablation.


Multiomic Analysis Identifies a High-Risk Metabolic and TME Depleted Signature that Predicts Early Clinical Failure in DLBCL.
60-70% of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients avoid events within 24 months of diagnosis (EFS24) and the remainder have poor outcomes. Recent genetic and molecular classification of DLBCL has advanced our knowledge of disease biology, yet were not designed to predict early events and guide anticipatory selection of novel therapies. To address this unmet need, we used an integrative multiomic approach to identify a signature at diagnosis that will identify DLBCL at high risk of early clinical failure. Tumor biopsies from 444 newly diagnosed DLBCL were analyzed by WES and RNAseq. A combination of weighted gene correlation network analysis and differential gene expression analysis followed by integration with clinical and genomic data was used to identify a multiomic signature associated with high risk of early clinical failure. Current DLBCL classifiers are unable to discriminate cases who fail EFS24. We identified a high risk RNA signature that had a hazard ratio (HR, 18.46 [95% CI 6.51-52.31] P < .001) in a univariate model, which did not attenuate after adjustment for age, IPI and COO (HR, 20.8 [95% CI, 7.14-61.09] P < .001). Further analysis revealed the signature was associated with metabolic reprogramming and a depleted immune microenvironment. Finally, WES data was integrated into the signature and we found that inclusion of ARID1A mutations resulted in identification of 45% of cases with an early clinical failure which was validated in external DLBCL cohorts. This novel and integrative approach is the first to identify a signature at diagnosis that will identify DLBCL at high risk for early clinical failure and may have significant implications for design of therapeutic options.


[One new chroman glycoside derivative from unmatured fruits of Citrus aurantium].
To study the chemical constituents of the unmatured fruits of Citrus aurantium. The AcOEt fraction of the methanol extracts of the unmatured fruits of C. aurantium were subjected on column chromatographies including silica gel, RP-18 and HPLC. Compound structures isolated were determined on the basis of spectroscopic data. Three compounds were isolated from the unmatured fruits of C. aurantium, which were identified as citrauranoside (1), limonexin (2) and limonin (3). Compound 1 is a new chroman glycoside derivative, named as citrauranoside.


Effects of replicative fitness on competing HIV strains.
We develop an n-strain model to show the effects of replicative fitness of competing viral strains exerting selective density-dependant infective pressure on each other. A two strain model is used to illustrate the results. A perturbation technique and numerical simulations were used to establish the existence and stability of steady states. More than one infected steady states governed by the replicative fitness resulted from the model exhibiting either strain replacement or co-infection. We found that the presence of two or more HIV strains could result in a disease-free state that, in general, is not globally stable.


A Bony Landmark 'RAI Triangle' to Prevent 'Misplaced and Misdirected' Medial Cut in SSRO.
'Rai triangle', a new anatomic landmark on the medial surface of the ramus of the mandible which when identified and taken into consideration, may have a definite advantage. This is especially in terms of performing the medial horizontal cut which is an important and integral part of the sagittal split ramus osteotomy so as to avoid a bad split. The objective of this article is to propose an easily identifiable bony land mark, which is closely related to lingula of mandible that may ease the procedure of osteotomy and avoid bad splits.


Long-Term Functional and Recurrence Outcomes of Surgically Treated Jugular Foramen Schwannomas: A 20-Year Experience.
To investigate the outcomes of jugular foramen schwannomas (JFSs) and to evaluate the risk factors for tumor recurrence and poor final outcomes. Between 1993 and 2013, 133 patients (68 female patients) with JFSs were surgically treated. Clinical charts were reviewed, and scheduled follow-up examinations were performed. The average preoperative Karnofsky Performance Scale (KPS) score was 79.6. The JFSs were classified as follows: 65 cases, type A; 15 cases, type B; 5 cases, type C; and 48 cases, type D. Gross total resection was achieved in 107 (80.5%) patients. Transient and permanent morbidities affecting cranial nerves IX and X were 19.8% and 11.5%, respectively. After a mean follow-up duration of 108.0 months, 13 (9.9%) patients experienced recurrence. The most recent KPS scores averaged 83.7. Compared with the preoperative KPS score, the most recent KPS score was improved in 87 (65.4%) patients and stabilized in 29 (21.8%) patients. The presence of a solid tumor (hazard ratio [HR] = 5.815, P = 0.010), nontotal resection (HR = 4.613, P = 0.007), and pathologic mitoses (HR = 11.018, P < 0.001) were independent risk factors for tumor recurrence. Decreased preoperative KPS score (per 10 points) (odds ratio [OR] = 2.483, P = 0.027), a less soft tumor consistency (OR = 2.257, P = 0.039), and a solid tumor (OR = 3.755, P = 0.041) were risk factors for poor long-term outcomes. Quality of life and preservation of neurologic function are the goals of surgical treatment of JFSs. Favorable long-term surgical outcomes for JFSs can be achieved. Morbidity of cranial nerves IX and X is significant, and patients with nontotal resection or pathologic mitosis should be followed closely.


Serum insulin-like growth factor I and ischemic brain injury.
Serum insulin-like growth factor I (IGF-I), which is mostly produced by the liver, has recently been shown to have the unexpected ability to modulate normal brain function as well as brain response to injury. Moreover, serum IGF-I levels are modified in many brain diseases, including stroke. However, whether these modifications are related to the disease process remains uncertain. We now examined a potential relationship between serum IGF-I and ischemic brain injury after middle cerebral artery occlusion (MCAo) and reperfusion in mice with either high or low serum IGF-I levels prior to insult. Surprisingly, we found that chronic high serum IGF-I correlates with increased brain infarct size following MCAo, while low levels correlate with reduced lesion size. Immunocytochemistry and immunoblot analyses revealed that levels of phosphorylated (i.e., activated) MAPK, known to be associated with the severity of ischemic brain injury, were increased in IGF-I treated mice. No overall effect of IGF-I treatment on IGF family mRNA expression in the brain was observed. Altogether, these results indicate that serum IGF-I levels negatively correlate with stroke outcome. Therefore, lowering serum IGF-I levels in aging mammals, including humans, may be beneficial against the increased risk of stroke associated to old age.


[Working poverty and self-rated health during the COVID-19 pandemic: a comparative study over time using 1995-2021 Socioeconomic Panel data].
The working poor are considered a vulnerable group. This study examines whether health disparities between working-poor and non-working-poor workers have worsened in the wake of the COVID-19 pandemic by comparing them over time with earlier periods of economic crisis and social and labor market policy reform. The analyses are based on the Socioeconomic Panel (SOEP, 1995-2020) and the Special Survey on Socioeconomic Factors and Consequences of the Spread of Coronavirus in Germany (SOEP-CoV, 2020-2021). All employed persons aged 18-67 years were considered for the analyses to calculate the risks of poor subjective health due to working poverty using pooled logistic regression by sex. Subjective health improved during the COVID-19 pandemic. Differences in health between the working poor and those who were not working poor remained relatively constant between 1995 and 2021. Individuals who were more likely to be in working poverty over time had the highest risk of inadequate health. The health disparities associated with the frequency of working poverty increased over time and peaked for both sexes in the pandemic. Significant sex differences were not identified. This study illustrates the social embeddedness of working poverty as a determinant of poor health. In particular, those who were more likely to experience working poverty during their working lives are considered to be particularly vulnerable to inadequate health. Tendentially, the COVID-19 pandemic appears to reinforce this gradient in health.


Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma: differential signaling mechanisms of TLR3-induced NF-kappaB activation and apoptosis.
Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). TLR3 expression and function in cancer cells are not well understood. We investigated the expression of TLR3 in hepatocellular carcinoma (HCC) cells and the function of TLR3 signaling by stimulation and transfection with polyinosinic-polycytidylic acid (Poly I:C), a synthetic form of dsRNA. TLR3 mRNA was expressed in HCC tissues as well as in non-tumor tissues. Positive immunohistochemical staining for TLR3 was observed in 52.7% of HCC tissues, and in HCC cells we found both membranous and cytoplasmic expression of TLR3. While cell surface stimulation of TLR3 with Poly I:C did not affect cell viability, it did activate NF-kappaB levels. In contrast, cytoplasmic stimulation with transfected Poly I:C significantly induced apoptosis accompanied by the down-regulation of anti-apoptotic protein. Transfected Poly I:C also synergistically augmented TRAIL-induced apoptosis, but only with low levels of transfected Poly I:C was IFN-beta production not observed. In conclusion, our results indicate that TLR3 expression in HCC plays an important role with regard to cell survival and proapoptotic activity. Endogenously expressed TLR3 may provide new clinical prospects for TLR3 agonists as cytotoxic agents in HCC.


Risk-based evaluation of the exposure of children to trace elements in playgrounds in Madrid (Spain).
Eighty samples of sandy substrate were collected in November 2002 and 2003, from 20 municipal playgrounds in Madrid (Spain) to assess the potential adverse health effects of the exposure of children to trace elements in this material during their games. In each playground, two 500 g samples were collected, dried at 45 degrees C for 48 h, sieved below 100 microm, acid digested and analyzed by ICP-MS. Doses contacted through ingestion and inhalation and the dose absorbed through the skin were calculated using USEPAs hourly exposure parameters for children and the results of an in situ survey. The toxicity values considered in this study were mostly taken from the US DoEs RAIS compilation. The results of the risk assessment indicate that the highest risk is associated with ingestion of soil particles and that the trace element of most concern is arsenic, the exposure to which results in a cancer risk value of 4.19 x 10(-6), close to the 1 x 10(-5) probability level deemed unacceptable by most regulatory agencies. Regarding non-cancer effects, exposure to playground substrate yields an aggregate Hazard Index of 0.28, below the threshold value of 1 (with As, again, as the largest single contributor, followed by Pb, Cr, Al and Mn). Although the uncertainties associated with the estimates of toxicity values and exposure factors should be reduced before any definite conclusions regarding potential health effects are drawn, risk assessment has proven to be a very useful tool to identify the contaminants and exposure pathways of most concern in urban environments.


Tunable Electrochemical Peptide Modifications: Unlocking New Levels of Orthogonality for Side-Chain Functionalization.
Electrochemical transformations provide enticing opportunities for programmable, residue-specific peptide modifications. Herein, we harness the potential of amidic side-chains as underutilized handles for late-stage modification through the development of an electroauxiliary-assisted oxidation of glutamine residues within unprotected peptides. Glutamine building blocks bearing electroactive side-chain N,S-acetals are incorporated into peptides using standard Fmoc-SPPS. Anodic oxidation of the electroauxiliary in the presence of diverse alcohol nucleophiles enables the installation of high-value N,O-acetal functionalities. Proof-of-principle for an electrochemical peptide stapling protocol, as well as the functionalization of dynorphin B, an endogenous opioid peptide, demonstrates the applicability of the method to intricate peptide systems. Finally, the site-selective and tunable electrochemical modification of a peptide bearing two discretely oxidizable sites is achieved.


The pressure-dependence of the size of extruded vesicles.
Variations in the size of vesicles formed by extrusion through small pores are discussed in terms of a simple model. Our model predicts that the radius should decrease as the square root of the applied pressure, consistent with data for vesicles extruded under various conditions. The model also predicts dependencies on the pore size used and on the lysis tension of the vesicles being extruded that are consistent with our data. The pore size was varied by using track-etched polycarbonate membranes with average pore diameters ranging from 50 to 200 nm. To vary the lysis tension, vesicles made from POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine), mixtures of POPC and cholesterol, and mixtures of POPC and C(16)-ceramide were studied. The lysis tension, as measured by an extrusion-based technique, of POPC:cholesterol vesicles is higher than that of pure POPC vesicles whereas POPC:ceramide vesicles have lower lysis tensions than POPC vesicles.


Development of a biomass torrefaction process integrated with oxy-fuel combustion.
Torrefaction of forest residues was studied under conditions relevant to oxy-fuel combustion flue gases. The results showed that the torrefaction in CO2 had a lower solid mass yield (81.36%) than that (83.06%) in N2. Addition of steam into CO2 (CO2/H2O=1/0.7 mole/mole) resulted in a higher mass yield (83.30%) compared to 81.36% in CO2. The energy yield was consistently increased from 79.17% to 84.12% or 88.32% for the torrefaction in N2, CO2, or the CO2 and steam mixture, respectively. On the other hand, additions of O2 into the mixture of steam and CO2 led to reductions in both mass yield (from 83.30% to 82.57% or 76.44%) and energy yield (from 88.32% to 84.65% or 79.16%, for the torrefaction in steam and CO2 without O2, with 5% v/v, or 10% v/v of O2, respectively).


Diagnostic and Prognostic Impact of Crypt Branching in Patients With Ulcerative Colitis: A Validation Study.
This study aimed to validate the inter-rater agreement of the assessment of crypt branching (also called crypt fission) in patients with ulcerative colitis (UC) and to elucidate its potential diagnostic and prognostic impact. A total of 100 biopsies from patients with UC were analyzed. Two cohorts of 50 patients each served as controls [infectious controls/controls with low grade intraepithelial neoplasia (LGIN) in UC alio loco]. Three pathologists scored the number of total crypts in fission as well as the number of crypts in symmetric (CSF) and asymmetric fission (CAF). Inter-rater agreement ranged from good to excellent in the study cohort. The number of crypts in fission correlated significantly with UC-activity (p=0.001; p<0.001). The study cohort showed higher mean counts of crypts in fission and significant more total and CAF than the infectious controls (p=0.007 and p=0.008), especially in male patients (p<0.001) The LGIN-control cohort showed significant more CSF (p=0.012). Inter-rater agreement for crypt branching was reliable in the study cohort. Crypt branching proved as an additional histologic feature to distinguish active UC against infectious colitis. Higher amounts of CSF may help identifying patients at higher risk for neoplasia.


Inflammatory impact of NOTES peritoneoscopy is not different from that of laparoscopy: a randomized comparative study in a survival porcine model.
Inflammatory changes of different NOTES approaches remain unknown. The aim of this study was to compare the inflammatory effects of NOTES and laparoscopy. Forty female pigs were assigned to transgastric, transrectal, and transvaginal NOTES and laparoscopic peritoneoscopy groups. Antiseptic technique was utilized for NOTES whereas laparoscopy was performed sterile. Intraperitoneal pressures were monitored and maintained below 15 mmH(2)O. Pneumoperitoneum was maintained with CO(2) in all groups. Pre- and postoperative blood samples of IL-6, Il-1β, and TNFα, and peritoneal fluid collected at surgery were analyzed. Animals were followed daily for 14 days. At necropsy, peritoneal fluid was collected for cytokine analysis. Thirty-nine peritoneoscopies were successfully completed. The median procedure time was longer in the NOTES groups (57 min, range = 33-109) than in the laparoscopy group (33 min, range 32-36; P < 0.001); this was related to longer incision time and closure time. All 39 completed follow-up. Severe bleeding in the post-transrectal approach required early sacrifice of the remaining animal. Besides this, complications were similar among groups. At necropsy, adhesions were seen in four animals in the gastric group, five in the rectal group, two in the vaginal group, and two in the laparoscopic group (P = ns). There were no statistical differences in serum levels of TNFα among the groups. When serum TNFα values were expressed as the difference from the baseline, in the transvaginal group they were significantly lower than in the transrectal at 2 h [0.5 pg/ml (range = -14 to 59) vs. 60 pg/ml (range = -8 to 303); P = 0.041] and at 8 h [-5.5 pg/ml (range = -86 to 55] vs. 37 pg/ml (range = -30 to 62); P = 0.031]. The limitations of this study were that the analyses of IL-6 and Il-1β were not possible because most of the samples were below detectable levels, it was an animal model, and the sample size was small. Inflammatory parameters are similar between NOTES and laparoscopic peritoneoscopy despite longer surgery time in the NOTES group. The vaginal route seems to reduce the inflammatory stress.


Ocular absorption of Pz-peptide and its effect on the ocular and systemic pharmacokinetics of topically applied drugs in the rabbit.
To determine the corneal and conjunctival penetration of 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (Pz-peptide) and to evaluate its effect on the corneal and conjunctival penetration of hydrophilic solutes as well as on the ocular and systemic absorption of topically applied atenolol and propranolol in the rabbit. The hydrophilic solutes were mannitol, fluorescein, FITC-dextran 4,000, and FITC-dextran 10,000. Drug penetration across the rabbit cornea and conjunctiva was evaluated using the modified Ussing chamber. Ocular and systemic absorption of topically applied atenolol and propranolol was evaluated by analyzing the drug concentration in various anterior segment tissues at 45 min and in the blood over 240 min, respectively, following topical instillation of 25 microl of 20 mM atenolol or propranolol solution to the rabbit eye. The conjunctiva was 29 times more permeable than the cornea to 3 mM Pz-peptide. Conjunctival Pz-peptide transport was 1.7 times more extensive in the mucosal-to-serosal than in the opposite direction, whereas corneal Pz-peptide transport showed no directionality. The apparent permeability coefficient of Pz-peptide across the cornea and the conjunctiva increased over the 1-5 mM range, suggesting that Pz-peptide enhanced its own transport across both epithelial tissues. The cornea appeared to be more sensitive than the conjunctiva to the penetration enhancement effect of Pz-peptide. Thus, whereas Pz-peptide elevated the corneal transport of mannitol, fluorescein, and FD4 by 50%, 57%, and 106%, respectively, it did not affect the conjunctival transport of mannitol and fluorescein, while enhancing FD4 transport by only 46%. Moreover, while Pz-peptide enhanced the ocular absorption of topically applied hydrophilic atenolol, it did not affect the ocular absorption of lipophilic propranolol. Interestingly, Pz-peptide did not affect the systemic absorption of either beta adrenergic antagonist. Pz-peptide appears to facilitate its own penetration across the cornea and the conjunctiva. Pz-peptide appears to increase the ocular absorption of topically applied hydrophilic but not lipophilic drugs, while not affecting the systemic absorption of either type of drugs.


Mechanistic aspects of electrochemical hydride generation for cadmium.
The mechanistic aspects of a novel methodology for the electrochemical hydride generation (EcHG) of cadmium, entitled as the catholyte variation, have been studied. The hydrogen overvoltage of different cathode materials was determined in dilute electrolyte. The lead-tin alloy used as the cathode material for the EcHG of Cd had the highest hydrogen overpotential. In this technique, both electrolyte medium and cathode surface would change during electrolysis. The catholyte variation EcHG coupled with a flame heated quartz tube atomizer (QTA) atomic absorption spectrometer (AAS) produced peak-shaped transient signal of Cd. The analytical signal was significantly enhanced at neutralization time. The simultaneous production of lead and tin hydrides as well as the hydrogen at that time may speed up the desorption of cadmium species from the surface of the cathode. Also the high hydrogen overvoltage and the neutral medium aided the formation and separation of cadmium hydride molecules. The generated CdH2 vapour was kinetically stable.


Twenty Years of Autologous Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma: A Single Portuguese Center Experience.
Diffuse large B-cell lymphoma can be cured in 60% - 70% of patients. Autologous stem cell transplantation is the standard treatment for relapsed disease. This high-intensity treatment after first complete remission in patients with high International Prognostic Index remains controversial and was performed in our department during some years. Retrospective study, review of clinical records. This study evaluates the outcome of 113 patients transplanted between 1992 and 2012. Considering status before transplantation patients were divided in groups: a) first complete remission after 1 line of chemotherapy (n = 64); b) first complete remission after ≥ two chemotherapy lines (n = 15); c) second complete remission (n = 15); d) more advanced diseased (n = 19). Chemotherapy used in first line therapy was mainly R-CHOP (n = 71) and CHOP (n = 28). The median follow-up of patients still alive was 34 months (1 - 221). At five years, overall survival was 73% (± 5) and disease free survival was 75% (± 5). Conventional chemotherapy followed by autologous stem cell transplant is a safe and efficient option for selected patients. In our series 70% high-risk patients were free from disease with this strategy.


Coated oral 5-aminosalicylic acid versus placebo in maintaining remission of inactive Crohn's disease. International Mesalazine Study Group.
A randomized, double-blind, placebo-controlled multicentre study was undertaken to evaluate the safety and efficacy of coated, oral 5-aminosalicylic acid (Mesasal/Claversal; 5-ASA) in maintaining remission of inactive Crohn's disease for up to 12 months. A total of 248 patients were entered from eight countries, of which 206 adhered to the protocol and were included in the analysis. The patients had Crohn's disease for an average of 5 years, with their disease clinically inactive for at least 1 month prior to entry into the study, and for an average of over 12 months previously. Thirty per cent of patients had had a previous resection, 16% of patients had been treated with sulphasalazine, while none of those analysed received glucocorticosteroids. Treatment consisted of 500 mg 5-ASA t.d.s. or placebo. 'Relapse' was defined as the first occurrence of Best's Crohn's Disease Activity Index greater than 150, which had increased 60 points from the pre-trial index. The cumulative life-table relapse estimate was lower in 5-ASA patients compared to placebo (22.4% vs 36.2%, respectively, Log rank test P = 0.0395). The 12-month relapse estimate in the 5-ASA group was also lower in patients with ileal disease (8.3% for 5-ASA and 31.0% for placebo, P = 0.0535) and in patients with previous bowel resections (14.2% vs 47.0%, P = 0.0436). The incidence of side-effects was similar in both treatment groups. It is concluded that 5-ASA was significantly superior to placebo in preventing relapse of Crohn's disease; this effect was most apparent in patients with disease restricted to the ileum and in patients with previous bowel resection. 5-ASA was well-tolerated, as demonstrated by a low incidence of adverse events.


Abnormal plasma amino acid profiles in patients undergoing bone marrow transplant.
Amino acid concentrations in plasma have been measured during total parenteral nutrition in patients undergoing bone marrow transplantation. Profound hyperaminoacidemia was noted in the immediate para-transplant period. The increase was due mainly to high levels of phenylalanine and methionine. During the radiation treatment period these amino acids plus valine, proline, serine and glycine were exceptionally high. Levels of cystine and asparagine tended to be low. The results suggest that infusion of a mixture of amino acids which is lower in phenylalanine and methionine might result in better nitrogen utilization.


Influence of heavy weight carrying on the cardiorespiratory system during exercise.
To study the influence of weight carrying on the cardiorespiratory system during dynamic exercise (walking) four conditions, i.e., rest, and treadmill exercise at 25, 50, and 75% of the individual VO2max, were combined with weight carrying of 10, 20, and 30 kg. In all experiments oxygen uptake, heart rate and pulmonary ventilation were measured. For each dynamic exercise condition and for the rest condition regression lines are calculated showing the relation between weight load an oxygen uptake, heart rate and pulmonary ventilation. From the slopes of these regression lines it can be seen that in rest (standing position) weight carrying does not influence oxygen uptake, heart rate and pulmonary ventilation. In dynamic exercise oxygen uptake, heart rate and pulmonary ventilation increase linearly with the amount of weight carried. To a large extent this increase is independent of the dynamic work load. In this study it was found that each kilogram extra weight increases oxygen uptake with 33.5 ml/min, heart rate with 1.1 beats/min and pulmonary ventilation with 0.6 1/min. In dyanmic work for loads higher than 50% of VO2max the relationship between weight carried and pulmonary ventilation is no longer a linear one. For the subjects studied it is assumed that oxygen consumption per kilogram weight is not different for body weight or extra weight carried.


Neurologic disease in Sjögren's syndrome: mononuclear inflammatory vasculopathy affecting central/peripheral nervous system and muscle. A clinical review and update of immunopathogenesis.
There is a growing appreciation that a subset of patients with primary Sjögren's syndrome (SS) also may develop a spectrum of central nervous system (CNS) complications. This article defines SS and its significance; discusses CNS, peripheral nervous system, and muscular complications of SS; identifies those areas in general or internal medicine in which SS patients with potential neurologic complications may present; describes those neurologic disorders that SS may mimic; places into perspective the controversy regarding the frequency and significance of CNS-SS; and extends our observations on the immunopathogenesis of neurologic complications in SS.


[Is the technique used to collect urine important in avoiding contamination of samples?].
To appraise the efficacy of hygienic standards in preventing the contamination of urine samples. Randomised clinical trial. 515 women assigned at random: 279 to the Intervention group and 236 to Control. Population registered with 4 doctors at 2 health centres. Women from 15 to 65 who attended the clinic for on-demand care. Criteria for exclusion from the trial were: permanent bladder catheter, anomalies in genito-urinary apparatus, antibiotic treatment in the 7 previous days and inability to understand instructions. Verbal instructions on hygienic standards for collecting the sample and explanatory leaflet, as against the customary guidelines. The main result was the combination of contamination levels and infection. Analysis by intention to treat. Irregularities in the urine culture in 113 (41%) patients from the Intervention group and in 133 (56%) from the Control group (P<.001), with RRR of 28% (95% CI, 14%-40%) and NNT of 6 (95% CI, 4-14). Taking only serious contamination or urinary infection, we had 14 in the Intervention group and 36 in the Control (P<.0001), with RRR of 67% (95% CI, 41%-82%) and NNT of 10 (95% CI, 6-20). Providing an explanatory leaflet and giving verbal instructions on hygienic standards for urine collection reduces contamination of the samples.


Labelling HaloTag Fusion Proteins with HaloTag Ligand in Living Cells.
HaloTag has been widely used to label proteins in vitro and in vivo (Los et al., 2008). In this protocol, we describe labelling HaloTag-Cbx fusion proteins by HaloTag ligands for live-cell single-molecule imaging (Zhen et al., 2016).


Preoperative segmental localization of colorectal carcinoma: CT colonography vs. optical colonoscopy.
Adequate preoperative segmental localization of colorectal cancer is important to indicate the right surgical treatment. Preoperative localization has become more important in the era of minimally invasive surgery. The aim of this study was to compare optical colonoscopy (OC) and CT colonography (CTC) with respect to the error rates in the segmental localization of colorectal carcinoma. A total of 420 patients with histopathologically proven colorectal carcinoma underwent CTC between December 2006 and February 2017. 284 Of these patients underwent surgical resection and had their carcinomas located on CTC report as well as OC report and surgical report. The segmental localization error rates of OC and CTC were compared using surgery as golden standard. McNemar's test was used to evaluate the differences in error rate. 284 Patients with a total of 296 colorectal carcinomas were evaluated. The segmental localization error rate of CTC (39/296, 13.2%) was found to be lower than the segmental localization error rate of OC (64/296, 21.6%) (p < 0.001). Per segment analysis showed that OC had a significantly higher error rate for carcinomas located in the descending colon (60.6% vs. 21.2% [p < 0.001] and cecum(60.0% vs. 23.3% [p = 0.001]). In 9.2% of the patients (26/284), localization based on CTC would lead to a change in surgical plan. CTC has a lower localization error rate than OC, which is most relevant for tumors located in the descending colon. If there is a doubtful localization on OC, particularly in the left-sided colon, an additional CTC should be performed to choose the best surgical treatment.


Effects of postnatal dietary choline manipulation against MK-801 neurotoxicity in pre- and postadolescent rats.
Prenatal supplementation of rat dams with dietary choline has been shown to provide their offspring with neuroprotection against N-methyl-d-aspartate (NMDA) antagonist-mediated neurotoxicity. This study investigated whether postnatal dietary choline supplementation exposure for 30 and 60 days of rats starting in a pre-puberty age would also induce neuroprotection (without prenatal exposure). Male and female Sprague-Dawley rats (postnatal day 30 of age) were reared for 30 or 60 concurrent days on one of the four dietary levels of choline: 1) fully deficient choline, 2) 1/3 the normal level, 3) the normal level, or 4) seven times the normal level. After diet treatment, the rats received one injection of MK-801 (dizocilpine 3mg/kg) or saline control. Seventy-two hours later, the rats were anesthetized and transcardially perfused. Their brains were then postfixed for histology with Fluorojade-C (FJ-C) staining. Serial coronal sections were prepared from a rostrocaudal direction from 1.80 to 4.2mm posterior to the bregma to examine cell degeneration in the retrosplenial and piriform regions. MK-801, but not control saline, produced significant numbers of FJ-C positive neurons, indicating considerable neuronal degeneration. Dietary choline supplementation or deprivation in young animals reared for 30-60days did not alter NMDA antagonist-induced neurodegeneration in the retrosplenial region. An interesting finding is the absence of the piriform cortex involvement in young male rats and the complete absence of neurotoxicity in both hippocampus regions and DG. However, neurotoxicity in the piriform cortex of immature females treated for 60days appeared to be suppressed by low levels of dietary choline.


Isotopes and sustainability of ground water resources, North China Plain.
Ground water in deep confined aquifers is one of the major water resources for agricultural, industrial, and domestic uses in the North China Plain. Detailed information on ground water age and recharge is vital for the proper management of these water resources, and to this end, we used carbon 14 of dissolved inorganic carbon and tritium in water to measure the age and determine the recharge areas of ground water in the North China Plain. These isotopic data suggest that most ground water in the piedmont part of the North China Plain is <40 years old and is recharged locally. In contrast, ground water in the central and littoral portions of the North China Plain is 10,000 to 25,000 years old. The delta18O (deltaD) values of this ground water are 1.7 per thousand (11 per thousand) less than that in the piedmont plain ground water and possibly reflect water recharged during a cooler climate during the last glaciation. The temperature of this recharge, based on delta18O values, ranges from 3.7 degrees C to 8.4 degrees C, compared to 12 degrees C to 13 degrees C of modern recharge water. The isotopic data set combined indicates that ground water in the central and littoral part of the North China Plain is being mined under non-steady state conditions.